count source_label source_id relationship target_label target_id entity_type solr_id publication_id sentences 80 UNIPROT:P00533 inhibits Neoplasms MESH:D009369 Protein 66955ff0-3816-11e6-8a17-001a4ae51247 PMC4367261 Furthermore, the ADCC-enhanced anti-HER2 × EGFR hetero-IgG1 V23_W165 significantly reduced the tumor size at the end of study when compared with the combination of two parent IgG1 antibodies (p= 0.0473), whereas the ADCC-norm anti-HER2 × EGFR hetero-IgG1 V23 did not show any significant difference (p= 0.2701).|||At the end of study (day 42), both anti-HER2 × EGFR hetero-IgG1 V23 and ADCC-enhanced anti-HER2 × EGFR hetero-IgG1 V23_W165 significantly reduced the tumor size when compared with the isotype human IgG1 control alone (p= 0.0266 and 0.0094, respectively) or anti-HER2 humAb4D5–8 IgG1 alone (p= 0.0441 and 0.0177, respectively).|||ADCC-enhanced anti-HER2 × EGFR hetero-IgG1 V23_W165 (p= 0.0162) significantly reduced the tumor size over the treatment, whereas anti-HER2 × EGFR hetero-IgG1 V23 having regular Fc region did not.|||These results showed that anti-HER2 × EGFR hetero-IgG1s strongly inhibited the tumor growth, and ADCC enhancement helps antibody to overcome K-RAS mutation, which is in line with the report by Schlaethet al.(46).|||To further investigate the mechanisms of tumor growth inhibition by anti-HER2 × EGFR hetero-IgG1 antibodies, Panc-1 cells of pancreatic adenocarcinoma carrying K-RAS mutation and expressing low HER2/EGFR were implanted in Rag2−/−/mFcγR4−/−/hCD16a+C57BL/6 transgenic mice. 64 Neoplasms MESH:D009369 activates MESH:D018450 Phenotype 2c5e01aa-04dd-11f0-bb39-0050569a791b 10.1016/j.bcp.2024.116254 By establishing a tight interplay with cancer cells and other TME components, tumor nerves contribute to promote disease progression and drug resistance. 64 Neoplasms MESH:D009369 activates GO:0042493 Phenotype 2c5e01aa-04dd-11f0-bb39-0050569a791b 10.1016/j.bcp.2024.116254 By establishing a tight interplay with cancer cells and other TME components, tumor nerves contribute to promote disease progression and drug resistance. 62 UNIPROT:P05121 inhibits Neoplasms MESH:D009369 Protein b0d40e4a-cb29-11e5-a6cd-001a4ae51247 11441025 This may also explain the apparent contradiction between the observation that high doses of PAI-1 can block tumor growth and angiogenesis (Figs.1and5), whereas PAI-1-deficient mice appear to show a reduced angiogenic response (Fig.5) (14,15,26).|||Since we have shown previously that PAI-1 is a potent inhibitor of vascular cell migrationin vitro(9) and angiogenesis in the chick CAMin vivo(10), we decided to test whether PAI-1 treatment could inhibit tumor growth in mice.|||Treatment with active PAI-1 decreased M21 tumor growth by ∼66% (p= 0.01) (Fig.1).|||PAI-1 Inhibits M21 Tumor Growth and Angiogenesis Because the growth of solid tumors requires an adequate blood supply, agents that block angiogenesis are likely to inhibit tumor growth. 56 UNIPROT:Q05516 inhibits Neoplasms MESH:D009369 Protein 7b27a308-c46a-11e5-85e4-001a4ae51246 PMC4081908 Knock-down of PLZF mRNA Inhibits Tumor Growth in a Mouse Xenograft Model As PLZF is overexpressed in human cancer tissues, PLZF may stimulate tumor growth by stimulating cell proliferation.|||We tested whether knock-down of PLZF mRNA can inhibit tumor growth in mouse (BALB/c-nu) xenografted with human clear cell renal cell carcinoma Caki-1 cells.|||As PLZF is overexpressed in human cancer tissues and knock-down of PLZF inhibits tumor growth in a mice xenograft model, PLZF may stimulate cell proliferation. 48 MESH:D000068579 activates Neoplasms MESH:D009369 Phenotype a2d6be66-45a7-11f0-9ac3-0050569a1f61 10.1016/j.jconrel.2022.03.043 Celecoxib successfully restored tumor blood flow byi) decompression of tumor vasculature via reducing tumor-associated fibroblasts and disrupting fibronectin bundles andii) normalization of tumor vascular structure via inhibiting angiogenesis and increasing pericyte coverage. 48 UNIPROT:Q96JB5 inhibits Neoplasms MESH:D009369 Protein 1a1adc44-5cba-11e7-8c5f-001a4ae51246 PMC4705989 For example, LZAP binds ARF (alternative reading frame) for p53 activation to suppress tumor growth (19) and, together with RelA, RCAD (regulators of C53/LZAP and DDRGK1 (DDRGK domain-containing protein 1), or NLBP (novel LZAP-binding protein) inhibits NFκB to suppress tumor invasion (17,63,64). 48 UNIPROT:P15941 inhibits Neoplasms MESH:D009369 Protein e7a94dfa-ea13-11ef-b449-0050569a791b 10.1016/j.colsurfb.2024.114321 Among them, siSIRPα enhanced the pMUC1-induced systemic cellular immunity, whereas pMUC1 enhanced the macrophages phagocytosis, M1-phenotype polarization, and tumor microenvironment remodeling mediated by siSIRPα, thereby inhibiting tumor growth and metastasis through combined immunotherapy. 48 UNIPROT:P17309 inhibits Neoplasms MESH:D009369 Protein d958422e-e851-11e5-acc1-001a4ae51246 10.1074/jbc.272.40.25367 Thus, it appears that RIII expression reduced both tumor incidence and tumor growth rate.|||Since our hypothesis was that RIII could antagonize the tumor-promoting activity of paracrine TGF-β by sequestering active TGF-β isoforms released by tumor cells, we inoculated exponentially growing cells of Neo pool, RIII pool, and RIII clone into athymic nude mice at 3 × 106cells per site and followed progression of xenograft formation. 48 FPLX:TGFB activates Neoplasms MESH:D009369 ProteinFamily d958422e-e851-11e5-acc1-001a4ae51246 10.1074/jbc.272.40.25367 Since our hypothesis was that RIII could antagonize the tumor-promoting activity of paracrine TGF-β by sequestering active TGF-β isoforms released by tumor cells, we inoculated exponentially growing cells of Neo pool, RIII pool, and RIII clone into athymic nude mice at 3 × 106cells per site and followed progression of xenograft formation.|||As a result, the TGF-β isoforms in these cells could act in a paracrine fashion to promote tumor growth. 48 CHEBI:4806 inhibits Neoplasms MESH:D009369 Chemical 3bc85b44-c46f-11e5-8491-001a4ae51247 PMC4239619 EGCG/PLX4720 treatment significantly suppressed tumor growth in mice compared with mice treated with EGCG or PLX4720 alone (Fig. 4,KandL).|||Silencing of SET significantly potentiated EGCG-induced suppression of tumor growth and increased survival rate (Fig. 3,GandH).|||To evaluate the influence of silencing SET on EGCG-induced tumor suppression, SET-knockdown B16 cells were injected subcutaneously into C57BL/6N mice. 48 UNIPROT:P05121 activates Neoplasms MESH:D009369 Protein b0d40e4a-cb29-11e5-a6cd-001a4ae51247 11441025 This suggested that low levels of active PAI-1 may promote tumor growth.|||The observation that PAI-1 can either enhance or inhibit tumor growth and angiogenesis depending upon its concentration may also explain why some studies have shown that PAI-1 is necessary for tumor growth (14,15,26), while others indicate that PAI-1 either has no affect (16) or is inhibitory (17).|||This confirms our hypothesis that PAI-1 at low doses can promote angiogenesis, whereas at higher concentrations it is inhibitory, and suggests that the reason that the partially inactivated PAI-1 stimulated tumor growth and angiogenesis was likely due to the 8% active PAI-1 present in the preparation. 40 Neoplasms MESH:D009369 activates GO:0001525 Phenotype c04da10e-5e79-11e6-ad98-001a4ae51247 10.1074/jbc.272.39.24294 Tumor-induced Angiogenesis To investigate the tumor-induced angiogenesis, modified CAM assay was carried out.|||However, neurotensin (250 pmol) used as a negative control peptide that has no relationship with angiogenin, did not inhibit the tumor-induced angiogenesis (data not shown).|||To investigate the tumor-induced angiogenesis, modified CAM assay was carried out. 40 UNIPROT:P21269 activates Neoplasms MESH:D009369 Protein 34f2c234-bbd5-11e5-9b9d-001a4ae51247 10.1016/j.uct.2006.04.004 In contrast, the TNT-1/leukotriene-B4, TNT-1/physalaemin, and TNT-1/bradykinin immunoconjugates produced an enhancement of antibody uptake in tumor only by altering the blood volume of the tumor vessels.|||The results of these studies, shown inTable 5, illustrate that TNT-1/IL-2 and TNT-1/histamine immunoconjugates produced an enhancement of antibody uptake in tumor only by altering the vascular permeability of the tumor vessels. 32 Neoplasms MESH:D009369 activates UNIPROT:Q5W0Z9 Protein af0398b2-37f6-11e6-b56c-001a4ae51246 PMC4505481 These results demonstrate that the mutations found in human tumor samples that reduce enzyme function also impair the ability of DHHC20 to suppress cell invasion. 32 Neoplasms MESH:D009369 activates UNIPROT:Q04609 Protein 2aee6a26-3406-11e8-87fd-001a4a160176 28887205 Peptidic tumor receptor ligands such as68Ga-DOTATOC, an agonist for somatostatin receptors typically overexpressed by G1/G2 neuroendocrine tumors[67], or68Ga-PSMA, a ligand for prostate-specific membrane antigen (PSMA) in prostate cancer[68]are also widely used for PET tumor imaging in both patients and experimental animal studies. 32 Neoplasms MESH:D009369 activates UNIPROT:P13611 Protein f8e5d766-c46e-11e5-8491-001a4ae51247 PMC4256343 Our findings that LMS tumor growth, tumor core necrosis, and mitotic index are dramatically reduced by decreasing the synthesis of versican further confirm the importance of the ECM in regulating cancer phenotype. 32 Neoplasms MESH:D009369 inhibits GO:0009058 Phenotype f8e5d766-c46e-11e5-8491-001a4ae51247 PMC4256343 Our findings that LMS tumor growth, tumor core necrosis, and mitotic index are dramatically reduced by decreasing the synthesis of versican further confirm the importance of the ECM in regulating cancer phenotype. 32 Neoplasms MESH:D009369 increases FPLX:Interferon ProteinFamily b6f9f49e-351a-11e8-a51f-001a4a160176 28647610 Specifically, STAT3 ablation in CD8+T cells resulted in up-regulated IFNγ expression, promoted CXCL10-dependent tumor infiltration and mitigated tumor progression of melanomain vivo[82]. 32 Neoplasms MESH:D009369 activates FPLX:Hedgehog ProteinFamily 96e38740-3387-11e8-87fd-001a4a160176 27619253 SHH enhances tumor growth via a paracrine pathway wherein the tumor-derived SHH ligand induces hedgehog targeting genes in the surrounding stroma. 32 Neoplasms MESH:D009369 activates UNIPROT:P04626 Protein e71e8dea-aba2-11e6-9646-001a4ae51246 PMC4597152 The Skyline file was exported to the mass spectrometer to build an SRM method, which was used to analyze FFPE tissue extracts from three different HER2-overexpressing tumors spiked with light and heavy-labeled synthetic peptides.|||Light and heavy-labeled versions of the peptide sequences which are proteotypic to HER2 and contain no methionine were synthesized (marked in italic inTable I) and spiked into peptide extracts originating from three FFPE tumors overexpressing HER2 and screened using an SRM method generated as described in the Materials and Methods section. 32 Neoplasms MESH:D009369 activates GO:0001525 Phenotype 3553d88c-f0ea-11ee-9aaa-0050569a1f61 10.1016/S1040-8428(03)00067-2 Although the mechanism by which EGFR regulates tumor biology in bladder cancer is not clearly defined, it has been demonstrated that EGFR signaling regulates cellular proliferation, differentiation, survival, invasion; and is implicated in the induction of tumor induced angiogenesis and metastasis[49].|||The abrogation of tumor growth was due to a reduction in tumor induced neovascularization secondary to the downregulation of tumor cell expression of the angiogenic factors VEGF, IL-8, and bFGF. 32 Neoplasms MESH:D009369 activates PF:PF01456 ProteinFamily c4bd9d54-ef47-11ee-b346-0050569a791b 10.1016/j.tgie.2004.03.013 IDUS was also useful in evaluating the feasibility of partial tumor resection in mucin-producing tumors of the ductal branches and pancreatic islet-cell tumors.|||In one study that included seven patients with mucin-producing tumors involving the MPD, IDUS identified abnormal areas that corresponded to adenomatous tissue or intraductal carcinoma, but could not distinguish between the 2.17A mural nodule was identified in 11 of 21 patients with ductal mucin-producing tumors; three patients had carcinoma, seven had adenoma, and one had hyperplasia. 32 MESH:D009536 activates Neoplasms MESH:D009369 Phenotype 284493c2-3528-11e8-a51f-001a4a160176 25205597 Apart from chemotherapy, carbogen and nicotamide have been used to enhance radiotherapy efficacy by reducing tumor hypoxia. 32 UNIPROTPRO:PRO:0000006688 inhibits Neoplasms MESH:D009369 Protein a2d6be66-45a7-11f0-9ac3-0050569a1f61 10.1016/j.jconrel.2022.03.043 Indeed, ACEi prevents the degradation of bradykinin, which can induce cancer growth and angiogenesis and promote tumor invasion and metastasis via stimulating matrix metalloproteases [262]. 32 FPLX:HDAC activates Neoplasms MESH:D009369 ProteinFamily 3493db58-1ad9-11f0-b759-0050569a791b 10.1016/j.bbcan.2024.189185 In most tumors, overexpression of HDAC can potentially lead to the downregulation of several tumor suppressive mechanisms, promoting oncogenic signaling events. 32 CHEBI:21241 inhibits Neoplasms MESH:D009369 Chemical 9018a41a-04c5-11f0-8fe6-0050569a1f61 10.1016/j.jddst.2024.105998 Notably, pharmacological concentrations of vitamin C or its derivatives can enhance H2O2levels to suppress tumor growth. 32 CHEBI:76604 activates Neoplasms MESH:D009369 Chemical b6c78a24-3752-11e8-9fbf-001a4a160176 23069141 Limited information is available from this study, given that it focuses on a structurally-similar compound, but not MelQ specifically; however, it is worth noting that while MeIQx caused tumors in other organs in mice or rats, it did not cause colorectal tumors. 32 FPLX:Pertussis:toxin inhibits Neoplasms MESH:D009369 ProteinFamily 56ecde40-e9e0-11ef-b449-0050569a791b 10.1016/j.ijpharm.2024.125050 Furthermore, investigation of the antitumor activity revealed that administration of free PTX and PTX-loaded nanogels inhibited tumor growth, whereas PBS-treated mice exhibited rapid tumor growth. 32 MESH:D004317 inhibits Neoplasms MESH:D009369 Phenotype 1858c23a-3749-11e8-a34b-001a4a160175 26432555 Sun et al., have shown that simultaneous delivery of ATRA and doxorubicin (DOX) through nanoemulsion, induced breast CSC differentiation, decreased number of breast CSCs in tumor and suppressed tumor growth by attenuating their tumor initiating ability[178]. 32 MESH:D009362 activates Neoplasms MESH:D009369 Phenotype fede7a5a-1c17-11f0-aa93-0050569a1f61 10.1016/j.mtbio.2023.100926 This combined strategy effectively inhibited the growth of primary tumor and distal tumor in 4T1 mouse models (98.41 % and 80.71 %), reduced the number and volume of lung metastases. 32 IP:IPR005556 activates Neoplasms MESH:D009369 ProteinFamily 1858c23a-3749-11e8-a34b-001a4a160175 26432555 Sun et al., have shown that simultaneous delivery of ATRA and doxorubicin (DOX) through nanoemulsion, induced breast CSC differentiation, decreased number of breast CSCs in tumor and suppressed tumor growth by attenuating their tumor initiating ability[178]. 32 MESH:D014212 activates Neoplasms MESH:D009369 Phenotype 1858c23a-3749-11e8-a34b-001a4a160175 26432555 Sun et al., have shown that simultaneous delivery of ATRA and doxorubicin (DOX) through nanoemulsion, induced breast CSC differentiation, decreased number of breast CSCs in tumor and suppressed tumor growth by attenuating their tumor initiating ability[178]. 32 UNIPROT:Q96EY5 activates Neoplasms MESH:D009369 Protein a0831562-86f5-11f0-9ac3-0050569a1f61 10.1016/j.jchromb.2020.122458 Most of the opines with available standard compounds were detected in the tumors when their presence was expected, except in three cases: cucumopine was not detected in extracts from tumors induced by strains CFBP 2407 and CFBP 2736, and agrocinopine A was not detected in the tumor caused by strain C58. 32 UNIPROT:P01133 activates Neoplasms MESH:D009369 Protein 637badde-354d-11e8-a51f-001a4a160176 15890525 This monoclonal antibody blocks the ligands EGF and TGF-alpha from binding to EGFR avoiding angiogenesis process, inhibiting tumor growth and eliciting both tumor regression and eradication of established tumors in murine xenograft tumor models[50]. 32 CHEBI:34608 activates Neoplasms MESH:D009369 Chemical 49201590-c477-11e5-a92e-001a4ae51246 26493004 For example, captan also causes duodenal tumors and hyperplasia in mice (but not rats) with a long time to tumor (NCI, 1977). 32 GO:0006954 activates Neoplasms MESH:D009369 Phenotype bec8b914-3405-11e8-a51f-001a4a160176 PMC5350633 (1)Evading Growth Suppressors: GO:0007049, Cell cycle; GO:0008283, Cell proliferation(2)Avoiding Immune Destruction: GO:0002682, Regulation of immune system process(3)Enabling Replicative Immortality: GO:0007568, Aging(4)Tumor-Promoting Inflammation: GO:0006954, Inflammatory response(5)Activating Invasion: GO:0034330, Cell junction organization(6)Inducing Angiogenesis: GO:0001525, Angiogenesis(7)Genome Instability: GO:0006281, DNA repair(8)Resisting Cell Death: GO:0012501, Programmed cell death; GO:0010941, Regulation of cell death(9)Deregulating Cellular Energetics: GO:0006091, Generation of precursor metabolites and energy(10)Sustaining proliferative signaling: GO:0007173, Epidermal growth factor receptor signaling pathway; GO:0048008, Platelet-derived growth factor receptor signaling pathway Evading Growth Suppressors: GO:0007049, Cell cycle; GO:0008283, Cell proliferation Avoiding Immune Destruction: GO:0002682, Regulation of immune system process Enabling Replicative Immortality: GO:0007568, Aging Tumor-Promoting Inflammation: GO:0006954, Inflammatory response Activating Invasion: GO:0034330, Cell junction organization Inducing Angiogenesis: GO:0001525, Angiogenesis Genome Instability: GO:0006281, DNA repair Resisting Cell Death: GO:0012501, Programmed cell death; GO:0010941, Regulation of cell death Deregulating Cellular Energetics: GO:0006091, Generation of precursor metabolites and energy Sustaining proliferative signaling: GO:0007173, Epidermal growth factor receptor signaling pathway; GO:0048008, Platelet-derived growth factor receptor signaling pathway For miRNAs which have been recently reported as cancer-related miRNAs and were not captured by GO analysis, association between these miRNAs and cancer hallmark traits is shown inFigure S7C according to the miRNA function described in OncomiRDB and literature search (Suzuki et al., 2015; Wang et al., 2014a). 32 UNIPROT:P05121 inhibits Neoplasms MESH:D009369 Protein 257f67d0-abb7-11e6-9ac8-001a4ae51246 PMC4587321 Overexpression of plasminogen activator inhibitor 1 (SERPINE1) in lymph node positiveversusnegative tumors supported the validity of the experiment and was specific for grade 3 tumors (p= 0.024 for grade 3versus p= 0.241 for grade 1,Table II). 32 UNIPROT:Q99626 inhibits Neoplasms MESH:D009369 Protein f58fdb52-c46e-11e5-a92e-001a4ae51246 PMC4246091 In contrast to the colon, somatic deletion of Cdx2 in the adult increased the incidence and growth of Min-induced tumors in the small intestine, but this was not exacerbated by concomitant deletion of Cdx1. 32 UNIPROT:P14209 activates Neoplasms MESH:D009369 Protein 9c9b25a2-054a-11f0-bb39-0050569a791b 10.1016/j.critrevonc.2024.104406 This leads to the expression of the EWS-FLI1 aberrant transcription factor which induces CD99 expression to promote tumor growth and metastasis. 32 UNIPROT:P52823 activates Neoplasms MESH:D009369 Protein 8b0a6e2c-001f-11f0-9f22-0050569a1f61 10.1016/j.jconrel.2024.11.076 For example, stanniocalcin 1 (STC1), an intracellular checkpoint that traps damage associated molecular patterns (DAMPs) such as calreticulin (CRT), inhibits DC phagocytosis and T cell activation and promotes tumor immune escape. 32 UNIPROT:P0A4K7 inhibits Neoplasms MESH:D009369 Protein 1b662300-1bad-11f0-85c3-0050569a1f61 10.1016/j.phrs.2024.107099 TET enhanced doxorubicin-mediated antitumor activity in mice carrying resistant MCF-1/DOX cells, thereby reducing tumor resistance without substantially increasing toxicity[220]. 32 UNIPROT:P04626 activates Neoplasms MESH:D009369 Protein ed7d9422-e831-11e5-96c9-001a4ae51247 10.1074/jbc.272.47.29482 In a subset of this study, we addressed the question of whether ribozyme-mediated abrogation of HER-2/neu expression can cause regression of established tumors. 32 CHEBI:9437 inhibits Neoplasms MESH:D009369 Chemical 240a8e52-bbda-11e5-9b9d-001a4ae51247 10.1016/S1011-1344(03)00020-4 On day 12 after treatment, tumor growth was reduced by 17% for SIM01 and 19% for m-THPC with a 6 h interval, and by 9% for SIM01 and 12% for m-THPC with a 12 h interval. 32 UNIPROT:P62745 inhibits Neoplasms MESH:D009369 Protein dc026662-cb8c-11e5-8106-001a4ae51247 10770919 Thus, the results of Fig.1Care in agreement with those of Fig.1Aand TableIand demonstrate that RhoB antagonizes tumor growth and suggest that RhoB-F is not a target for the antitumor activity of FTIs in human cancer cells.|||The ability of RhoB to suppress Panc-1 cell tumor growth in nude mice requires prenylation by either farnesyl or geranylgeranyl because a RhoB mutant that lacks a CAAXbox did not inhibit tumor growth (Fig.4). 32 UNIPROT:P51654 inhibits Neoplasms MESH:D009369 Protein 7ece1faa-1b86-11f0-aa93-0050569a1f61 10.1016/j.intimp.2024.112011 Furthermore, GPC3-positive HCC cells are eliminated by CAR (hYP7) T cells in mice with xenograft or orthotopic liver tumors.|||Another study developed patient-derived xenograft (PDX) HCC models and showed that GPC3 CAR-T cells inhibited tumor growth; however, the effectiveness of these agents varied according to PDL1 expression on tumor cells[161]. 32 UNIPROT:Q9LDE2 inhibits Neoplasms MESH:D009369 Protein a6c93254-1bb0-11f0-aa93-0050569a1f61 10.1016/j.phymed.2024.155444 BBR significantly reduced the tumor weight of MGC803 and SGC7901 subcutaneously transplanted tumors in mice, with a reduction rate of approximately 50.0% and 60.9% of that of the control group, respectively (Li et al., 2022c).|||BBR significantly decreased tumor volume and tumor weight in human gastric cancer cell lines MGC803 xenograft mice (Li et al., 2020c). 32 UNIPROT:P10451 activates Neoplasms MESH:D009369 Protein 9b856b66-cb28-11e5-a6cd-001a4ae51247 11564733 The levels of both the pro and active forms of MMP-2 in the tumors produced by OPN (10.0 μm) were significantly higher (panel a,lane 2) compared with the levels of MMP-2 in the tumors in non-OPN-injected mice (lane 1).|||The weights of the OPN-induced tumors were increased at least 3.1-fold compared with the tumors of the non-OPN-injected mice (TableI). 32 UNIPROT:P62937 activates Neoplasms MESH:D009369 Protein 64b7e3f0-c8e6-11e5-a1fd-001a4ae51246 17991918 In addition, CypA expression increased nearly 5-fold in 15-week 12T-7f tumors compared with age-matched normal controls, correlating with the increase in CypA expression observed by immunohistochemical analysis.|||CypA staining was similar in 12T-7f prostate tumors; however, the intensity of nuclear and cytoplasmic CypA immunoreactivity increased, suggesting that CypA expression was elevated in the tumors (Fig. 10L). 32 MESH:D013755 activates Neoplasms MESH:D009369 Phenotype daa0ea14-cb8c-11e5-a7a8-001a4ae51246 10747974 The induction was almost as strong as that caused by the tumor promoter TPA (compare Fig.8,lanes 3and4).|||H. pyloriinduced Elk-1 phosphorylation as strongly as the tumor promoter TPA (Fig.7, comparelanes 3and5). 32 MESH:D051379 inhibits Neoplasms MESH:D009369 Phenotype 25583e3e-12d9-11f0-b759-0050569a791b 10.1074/jbc.272.17.11597 Treatment of the mice 36 h after cell injection, prevented tumor development in a dose-dependent manner (Fig. 8).|||A dosage of 5 μg/day/mouse GnRH-PE66inhibited tumor growth in 40% of the mice, while 10 μg/day/mouse prevented appearance of the tumors in 80% of the animals. 32 MESH:D000860 activates Neoplasms MESH:D009369 Phenotype d4aba2be-ab9e-11e6-9236-001a4ae51247 PMC4571963 Hypoxia-induced up-regulation of VEGF is a primary driver of tumor angiogenesis, but because the resulting aberrant vasculature does not correct the hypoxia, VEGF expression continues unabated (31).|||This revealed that the average intensity of the hypoxia signal in FGF9-modified tumors was 33% lower than that in control tumors (p= 0.031,Fig. 6). 32 UNIPROT:P04637 activates Neoplasms MESH:D009369 Protein 003333aa-8667-11f0-afc2-0050569a791b 10.1016/j.bcp.2021.114407 ARF tumor suppressor protein (P14ARF) can promote the degradation of MDM2 through the proteasome pathway and stabilize the p53 protein, thus playing an important role in p53-mediated stress induced by tumor-promoting factors[59].|||P52-ZER6 can enhance the binding of MDM2 and p53, promote p53 ubiquitination, and promote tumor progression[79]. 32 UNIPROT:P16070 activates Neoplasms MESH:D009369 Protein b4173e82-ca5d-11e5-8050-001a4ae51246 12511569 To investigate whether increased expression of E-cadherin may affect CD44-mediated tumor invasion as well, G8 myoblast monolayer invasion assay was performed as described previously (17,18).|||CD44-mediated Tumor Invasion Is Negatively Regulated by E-cadherin It has been shown that CD44-HA interaction is essential for CD44-mediated tumor invasion (17,18). 32 UNIPROT:P36575 inhibits Neoplasms MESH:D009369 Protein eddab220-e9e3-11ef-b449-0050569a791b 10.1016/j.yexcr.2024.114391 These CAR T cells effectively eliminated the GPC3-positive tumors by suppressing the growth of the tumor in PDX3 and almost completely eliminating the malignancies in PDX1 and PDX2, where GPC3 expression was high [106].|||In HCC xenograft models, third-generation CAR T cells eliminated tumors with elevated GPC3 expression, inhibited the growth of low-expression tumors, and markedly increased the survival of mice receiving orthotopic Huh-7 xenografts [100]. 32 CHEBI:16336 activates Neoplasms MESH:D009369 Chemical 46911f6a-cb28-11e5-b419-001a4ae51246 11717318 However, the clinical significance of hyaluronan levels appears different from those of simple epithelia because local decreases in the cell-associated hyaluronan signal in these tumors correlate with poor histologic differentiation and prognosis (9,10).|||Thus penetration of hyaluronan-rich stroma (25) or production of angiogenic breakdown products of hyaluronan (32) may also promote tumor progression. 32 MESH:D008407 activates Neoplasms MESH:D009369 Phenotype d1467d04-340c-11e8-87fd-001a4a160176 24671125 Moreover, under certain conditions, MCs and basophils can activate T lymphocytes by functioning as antigen presenting cells, and thereby potentially modulating tumor rejection.|||On the other hand, MCs may promote tumor growth, exerting immunosuppression through the production of TNF-α and IL-10 (Grimbaldeston et al., 2007). 32 UNIPROT:P31371 activates Neoplasms MESH:D009369 Protein d4aba2be-ab9e-11e6-9236-001a4ae51247 PMC4571963 Interestingly, there was no evidence that FGF9 stimulated angiogenesis in the renal tumor.|||Collectively, these data establish that FGF9 can drive a microvessel maturation program in renal tumors, without stimulating angiogenesis, and that this program entails vessel fortification by pericytes, SMCs, and an enriched basement membrane. 32 UNIPROT:P42858 activates Neoplasms MESH:D009369 Protein bf1f98be-bc03-11e5-8abe-001a4ae51246 10.1016/j.fct.2008.06.027 2 In this study an in vivo hyaline droplet (HD) formation ability of various terpenes was investigated because chemicals that exacerbate HD (protein) accumulation also produce renal tubular tumors.|||In this study an in vivo hyaline droplet (HD) formation ability of various terpenes was investigated because chemicals that exacerbate HD (protein) accumulation also produce renal tubular tumors. 32 UNIPROT:O14756 activates Neoplasms MESH:D009369 Protein 564c5f82-cb28-11e5-a6cd-001a4ae51247 11313348 As shown in TableIII, HSE-induced tumor cytotoxicity was significantly higher in B16M cells pre-cultured to high density, a fact that is in agreement with our previous observations (24,25).|||HSE-induced tumor cytotoxicity in BSO-treated LD B16M cells was similar to that found in HD B16M cells, whereas HSE-induced tumor cytotoxicity in GSH ester-treated HD B16M cells decreased to values similar to those found in control LD B16M cells (TableIV). 32 UNIPROT:Q9BYI3 inhibits Neoplasms MESH:D009369 Protein 7ece1faa-1b86-11f0-aa93-0050569a1f61 10.1016/j.intimp.2024.112011 Furthermore, because combined therapy with DC vaccination and a PD-1 inhibitor induces T-cell cytotoxicity, improves OS, reduces tumor volume, and increases tumor cell apoptosis in HCC mice, this combination may constitute a viable therapeutic approach for HCC.|||Furthermore, GPC3-positive HCC cells are eliminated by CAR (hYP7) T cells in mice with xenograft or orthotopic liver tumors. 32 UNIPROT:P07737 inhibits Neoplasms MESH:D009369 Protein 7bf36102-380d-11e6-aaca-001a4ae51246 PMC4423694 We conclude that Pfn1(wt) might inhibit tumor growth through the effects on proliferation and apoptosis together, whereas Pfn1(S137A) functions mainly by sensitization to apoptosis.|||Although Pfn1 inhibits tumor growth by influencing both proliferation and apoptosis, these two functions of Pfn1 appear to be differentially regulated by Ser-137 phosphorylation. 32 UNIPROT:Q13886 inhibits Neoplasms MESH:D009369 Protein 22cd3574-c46f-11e5-85e4-001a4ae51246 PMC4239625 We found previously that KLF9 induction reduces the growth of intracranial tumor xenografts established from GBM neurospheres and extends the survival of mice bearing xenograft tumors (31).|||However, integrin α6 expression rescued tumor growth inhibition induced by KLF9 (Fig. 8,BandC). 32 UNIPROT:P08922 activates Neoplasms MESH:D009369 Protein 4e1dbaf0-45a7-11f0-8978-0050569a1f61 10.1016/j.jconrel.2022.03.024 The redox environment in TME has been noted as a double-edged sword to tumor cells, whereby the generation of ROS results in oxidative stress to healthy tissues to promote tumor progression, while excess ROS could lead to tumor elimination [158,159].|||The GSH depletion in the TME is desirable to enable the chemotherapy or ROS-induced elimination of tumor. 32 CHEBI:53074 inhibits Neoplasms MESH:D009369 Chemical 651a5d28-5cb5-11e7-bcb7-001a4ae51246 PMC4714189 Notably, DpC had totally inhibited tumor growth after this treatment period, with no significant (p> 0.05) difference observed in tumor size between days 0 and 23.|||In this study, Dp44mT and DpC significantly (p< 0.001–0.01) decreased PANC-1 tumor growth to 29.9 ± 8.8% (n= 6) and 19.3 ± 1.4% (n= 6) of the control, respectively, after 23 days (Fig. 11A). 32 CHEBI:37532 activates Neoplasms MESH:D009369 Chemical 93c068b0-cb2b-11e5-b419-001a4ae51246 12084710 Effects of Staurosporine on the Oligomerization and Translocation of DGKδ In addition to PKC, many proteins, for example, avavoncogene product, chimerins, and Ras guanyl nucleotide-releasing proteins have been reported to be activated by tumor-promoting phorbol ester (3,4).|||In addition to PKC, many proteins, for example, avavoncogene product, chimerins, and Ras guanyl nucleotide-releasing proteins have been reported to be activated by tumor-promoting phorbol ester (3,4). 30 Neoplasms MESH:D009369 activates UNIPROT:P48023 Protein 403e56b6-2cab-11f0-aa93-0050569a1f61 10.1016/S1568-9972(01)00014-3 Thus, interferon-γ and tumor necrosis factor-α were able to upregulate surface Fas and Fas ligand, whereas interleukin 1-β downregulated surface Fas ligand. 28 Neoplasms MESH:D009369 decreases UNIPROT:Q9NQU5 Protein e5424d24-5cbc-11e7-bcb7-001a4ae51246 PMC4653705 Decreased PAK6 Expression Predicts Poor Survival in HCC Patients To investigate the role of PAK6 in HCC, the PAK6 mRNA level was first evaluated in tumor and adjacent paired non-tumor tissues. 28 UNIPROT:P31371 inhibits Neoplasms MESH:D009369 Protein d4aba2be-ab9e-11e6-9236-001a4ae51247 PMC4571963 FGF9 Suppresses Metastases of Renal Tumors in Mice To investigate the impact of FGF9 delivery on tumor vessels, we sought to study a tumor in which FGF9 would have little to no direct effect on the tumor cells themselves. 26 Neoplasms MESH:D009369 activates GO:0006954 Phenotype 5d996c8c-c46e-11e5-9cc6-001a4ae51246 24632289 Major Cancer Hallmarks affected by ING4 (Fig. 2): •immune destruction,•tumor promoting inflammation,•angiogenesis.|||immune destruction, tumor promoting inflammation, angiogenesis.|||In addition to various cancer hallmarks affected by all ING family proteins, ING4 is the one that has been reported to additionally affect tumor promoting inflammation and immune destruction. 24 GO:0006955 activates Neoplasms MESH:D009369 Phenotype a9c0d782-45db-11f0-afc2-0050569a791b 10.1016/j.ejpb.2022.03.002 PDT-induced immune response and gene therapy-induced PD-L1 blockade synergistically inhibit tumor growth, thereby reducing the tumor recurrence rate to 25%. 24 FPLX:Pertussis:toxin inhibits Neoplasms MESH:D009369 ProteinFamily af5f514e-390b-11e8-87fd-001a4a160176 25445692 Intriguingly, we found that although both PEG-Lip/PTX and PEG-Lip/antagomir-10b+PTX could inhibit the tumor growth to some extent, D-Lip/PTX and D-Lip/antagomir-10b+PTX could induce more tumor volume reduction when compared with them (Fig. 8A). 24 UNIPROT:P41159 activates Neoplasms MESH:D009369 Protein a94ba1e8-3aa7-11e8-8636-001a4a160175 27671038 They found that obesity promotes melanoma tumor growth, regardless of the presence or absence of leptin suggesting that leptin is not essential for tumor growth; energy restriction attenuates tumor growth in obese mice; leptin may accelerate tumor growth while leptin deficiency in the absence of obesity attenuates tumor growth; leptin receptors are expressed in mouse melanoma cells and there are a significantly increase in the proliferation of cultured B16-F10 cells. 24 MESH:D015735 activates Neoplasms MESH:D009369 Phenotype 786eb826-1b28-11f0-b759-0050569a791b 10.1016/j.jsbmb.2024.106515 The combination of suboptimal doses of mifepristone with the PD-L1 blockade increased tumor regression as compared to both monotherapies in the sensitive mouse model, suggesting that antiprogestins induce tumor changes in PRA-H tumors that may prime them for immunotherapy[122]. 24 MESH:D005291 inhibits Neoplasms MESH:D009369 Phenotype c5a991a8-1c1b-11f0-b759-0050569a791b 10.1016/j.critrevonc.2024.104262 A recent study revealed that ferrichrome derived from probiotic Lactobacillus casei can suppress tumor growth by altering the proportion of M1/M2 TAM, increasing the infiltration of CD8 +T cells in tumors, and reprogramming pancreatic TME, thus enhanced tumor immune surveillance and responsiveness to immune checkpoint inhibitors (Chaib et al., 2022). 24 UNIPROT:Q9NR71 inhibits Neoplasms MESH:D009369 Protein e5ff92fc-1b5a-11f0-b759-0050569a791b 10.1016/j.critrevonc.2024.104359 There is evidence that these tumor-infiltrating MDSCs prevent ferroptosis by overexpressing systemic Xc-and neutral ceramidase N-acylsphingosine amidohydrolase 2 (ASAH2) (Zhu et al., 2021). 24 UNIPROT:P48061 activates Neoplasms MESH:D009369 Protein 41b3f514-0041-11f0-9f22-0050569a1f61 10.1016/j.mad.2024.112009 For instance, CXCL12 (SDF-1)-CXCR4 signaling mediate immune cell tumor trafficking―chemotactic mobilization of plasmacytoid DC into tumors and Tregcell into bone marrow microenvironment, facilitating tumor vascularization, metastasis, and growth (Teicher and Fricker, 2010). 24 UNIPROT:P60568 inhibits Neoplasms MESH:D009369 Protein 298fa56a-cb2a-11e5-9aa0-001a4ae51247 11991739 In two studies using mouse models of hepatic metastasis, coexpression of interleukin-2 (IL-2) as well as IL-2 plus granulocyte macrophage colony stimulating factor (GM-CSF) with HSV1-TK significantly decreased tumor volume [9,10]. 24 UNIPROT:P17931 activates Neoplasms MESH:D009369 Protein af308af0-0017-11f0-a3d5-0050569a1f61 10.1016/j.canlet.2024.217399 (2)Galectin-3 (Gal-3) Galectin-3 (Gal-3) Gal-3 regulates the TME through multiple mechanisms and promotes tumor immune escape. 24 CHEBI:4027 inhibits Neoplasms MESH:D009369 Chemical 7c16db92-1bf1-11f0-b759-0050569a791b 10.1016/j.bbcan.2023.189062 Nevertheless, in a neuroblastoma xenograft model, metronomic cyclophosphamide combined with MCT-supported KD suppressed tumor growth and reduced tumor blood vessel density [177]. 16 Neoplasms MESH:D009369 activates UNIPROT:Q99683 Protein 3e6ec5fc-a1a7-11e6-9b40-001a4ae51246 10.1074/jbc.273.43.27816 In addition, ASK1 is activated by tumor necrosis factor-α and induces apoptosis (14). 16 Neoplasms MESH:D009369 inhibits UNIPROT:P62745 Protein dc026662-cb8c-11e5-8106-001a4ae51247 10770919 The tumor growth suppressor activity of RhoB was also p53-independent because some of the human cancer cell lines used have nonfunctional p53. 16 Neoplasms MESH:D009369 increases UNIPROT:Q68D85 Protein 8910188a-5cba-11e7-8b40-001a4ae51247 PMC4705966 To validate our proposal that increased B7-H6 expression induced by tumor therapeutics also participate in tumor sensitivity to NK cell cytolysis, anti-NKp30, and anti-NKG2D blocking antibodies were used during cytolysis. 16 Neoplasms MESH:D009369 activates UNIPROT:P35354 Protein fea9a7fa-cb89-11e5-9498-001a4ae51246 10692422 Five deletion and site-directed mutagenesis studies in MC3T3-E1 osteoblasts have suggested the involvement of a NF-IL6 site in the induction of the COX-2 promoter by tumor necrosis factor-α (41,42). 16 Neoplasms MESH:D009369 inhibits UNIPROT:P11926 Protein 22d27d72-1b13-11f0-b759-0050569a791b 10.1016/j.biopha.2024.116862 Baicalein could inhibit skin tumor progression in B[a]P-induced and 12-O-tetradecanoylphorbol-13-acetate (TPA)-promoted tumor model through suppressing TPA-induced production of the H2O2and myeloperoxidase (MPO), ornithine decarboxylase (ODC) activity and inflammatory responses[177]. 16 Neoplasms MESH:D009369 activates UNIPROT:O75582 Protein bb9bf0a0-cbf0-11e5-83a8-001a4ae51246 9873047 As shown in Fig.3A, RLPK activity was significantly stimulated by 12-myristate 13-acetate, EGF, and serum, while the proinflammatory cytokine tumor necrosis factor-α and cell stress stimuli calcium ionophore A23187, anisomycin, and arsenite also increased RLPK activity, but to a lesser extent. 16 Neoplasms MESH:D009369 activates UNIPROT:Q04609 Protein 647f8b60-0539-11f0-bb39-0050569a791b 10.1016/j.biopha.2024.117125 Mice bearing PSMA-producing LNCaP tumors were intravenously administered a once weekly dose of one of: (i) PBS, (ii) blank nanoparticle control, (iii) combination docetaxel and brusatol-loaded nanoparticles, (iv) brusatol-loaded nanoparticles and (v) docetaxel-loaded nanoparticles, through the tail vein for a total of 2 weeks (Table 2). 16 Neoplasms MESH:D009369 increases UNIPROT:P56817 Protein 4e5d9044-c46f-11e5-9cc6-001a4ae51246 PMC4256331 Tumor necrosis factor-α (TNFα) has been shown to induce BACE-1 expression and to contribute to brain accumulation of Aβ peptides (43). 16 Neoplasms MESH:D009369 activates UNIPROT:P59510 Protein de2670a4-ca5c-11e5-9bd2-001a4ae51247 12562771 To examine the possibility that ADAMTS-20 was produced by human tumors, we performed RT-PCR amplification with RNAs obtained from a panel of paired primary tumors and adjacent normal tissue. 16 Neoplasms MESH:D009369 increases UNIPROT:Q9NZQ7 Protein d3f3c67a-1b53-11f0-b759-0050569a791b 10.1016/j.arr.2024.102314 Neutrophils' PD-L1 expression was triggered and increased by tumor-derived CCL20 (Kwantwi et al., 2021). 16 Neoplasms MESH:D009369 phosphorylatesProtein UNIPROT:P33151 Protein 62efaca6-c477-11e5-85e4-001a4ae51246 PMC4732197 Therefore, we determined whether the changes in VE-cadherin phosphorylation induced by tumor-derived thrombin were associated with p120 phosphorylation. 16 Neoplasms MESH:D009369 inhibits UNIPROT:Q9T041 Protein e7dbbf10-d6b8-11e5-8cf6-001a4ae51246 9867815 Notably, both tumor necrosis factor-α (50 ng/ml) and interferon-γ (50 units/ml) elicited an inhibition of CN activity of about 25% after 2 h of treatment. 16 Neoplasms MESH:D009369 increases UNIPROT:Q15389 Protein ac78e2f8-cb29-11e5-b419-001a4ae51246 11447223 When Tie-2 receptors on local endothelial cells are saturated, it is likely that the excess amount of Ang-1 produced by the primary tumors would be incorporated into and sequestered by the surrounding ECM, whereas the excessive amount of Ang-2 may diffuse to distant organs. 16 Neoplasms MESH:D009369 decreases UNIPROT:P42330 Protein 931651a6-aba2-11e6-9236-001a4ae51247 PMC4543648 Western blot analysis showed that Siah2 KD reduced AKR1C3 levels in the Rv1 tumor tissues from both castrated and control mice (Fig. 1C), indicating that Siah2 promotes the expression of AKR1C3 protein under both castration and normal conditions. 16 Neoplasms MESH:D009369 activates UNIPROT:P51948 Protein bbcf4444-ca5d-11e5-9088-001a4ae51247 12527756 In 6 of the MAT1-overexpressing tumors, there was also up-regulation of MTA1. 16 Neoplasms MESH:D009369 increases UNIPROT:P42574 Protein 28377836-3804-11e6-8a17-001a4ae51247 PMC4409274 Because we find that conditioned medium from cultured C26 cancer cells stimulates caspase-3 expression and activation in skeletal muscle cells (Fig. 1), we examined whether C26 or LLC tumors inoculated in mice will stimulate caspase-3 expression and activation in muscle.Fig. 16 Neoplasms MESH:D009369 increases UNIPROT:P01308 Protein 80f36014-cbf0-11e5-a19a-001a4ae51247 10567411 Using the same treatment protocols previously reported for stimulation of insulin release from βTC-3 cells (20), we examined the effect of calbindin overexpression on insulin release stimulated by depolarizing concentrations of potassium as well as by TPA (a tumor promoting phorbol ester and activator of protein kinase C whose actions on the β cell have been linked with membrane depolarization, 35). 16 Neoplasms MESH:D009369 activates UNIPROT:Q99538 Protein dc07d778-cbf0-11e5-b0dd-001a4ae51247 10488118 Animals bearing legumain-producing tumors and treated with vehicle had similar numbers of OCLs and bone-resorbing surfaces as mice bearing control tumors. 16 Neoplasms MESH:D009369 activates UNIPROT:P00533 Protein 5490e50e-3409-11e8-9fbf-001a4a160176 25813885 These authors, using a first-line cytotoxic agent (cisplatin), and a targeting moiety (epidermal growth factor, EGF) conjugated to the sidewall of single-walled nanotubes (SWNTs), have shown an enhanced efficacy to target squamous cancer cells that overexpress the epidermal growth factor receptor (EGFR), increased accumulation and uptake of the nanotubes by the tumor tissue, and an augmented efficacy to reduce the size of a head and neck tumor, compared with untargeted nanotubes without EGF molecules[320,321]. 16 Neoplasms MESH:D009369 activates UNIPROT:P04004 Protein e9097e7c-d6b8-11e5-9ef6-001a4ae51247 9867852 Vitronectin is synthesized and secreted by tumor-associated fibroblast-like cells (65), suggesting that vitronectin expression can be induced in disease states such as cancer. 16 Neoplasms MESH:D009369 activates UNIPROT:P05231 Protein af97e462-cb8c-11e5-984a-001a4ae51247 11084045 This putative STAT site might well mediate the effects of IFN-γ and/or prolactin, both proven inducers of MUC1 expression, and IL-6 which is often produced by solid tumors, including breast carcinomas (see Introduction). 16 Neoplasms MESH:D009369 increases UNIPROT:P19838 Protein af3d1268-d431-11e6-a821-001a4ae51247 10.1074/jbc.272.35.21774 Late autoregulated transcription is probably indirectly induced following either form of stimulation, as reported for the TcR/CD3-mediated delayed increase in p50 and c-Rel mRNA levels through autocrine secretion of the NF-κB inducer, tumor necrosis factor-α (39,49). 16 Neoplasms MESH:D009369 activates UNIPROT:P00918 Protein d580a628-0557-11f0-9c9e-0050569a1f61 10.1016/j.bioactmat.2024.04.007 In the tumor environment, DMA continuously inhibits Ca2+ influx into cells, suppressing Ca2+-controlled exosome release. 16 Neoplasms MESH:D009369 activates UNIPROT:P02751 Protein dc621e3a-ca5c-11e5-a3f7-001a4ae51246 12582155 This indicates that FN13 is able, to a varying extent, to promote the formation of an FN network surrounding transformed and tumor-derived cells. 16 Neoplasms MESH:D009369 increases UNIPROT:P48023 Protein f0b21a6e-8791-11f0-afc2-0050569a791b PMC7714955 For example, tumor endothelial cells upregulated the expression of Fas ligand (FasL) in response to the stimulation of tumor-derived VEGF, IL-10 and prostaglandin E2, which has been demonstrated to selectively kill effector CD8+T cells but not Tregs15,76. 16 Neoplasms MESH:D009369 increases UNIPROT:P48023 Protein c482c8b2-1be9-11f0-b40b-0050569a1f61 10.1016/j.bbcan.2024.189079 Tumor-derived factors like VEGF-A, IL-10, and PGE2 induce FasL expression, selectively eliminating effector CD8+ T cells while sparing Treg cells [94,96]. 16 Neoplasms MESH:D009369 decreases UNIPROT:P31751 Protein 15575fee-c476-11e5-9da3-001a4ae51247 PMC4742769 In addition, treatment with bexarotene significantly alleviated the impairment of Akt2 expression caused by tumor-derived factors (Fig. 8,DandF). 16 Neoplasms MESH:D009369 inhibits UNIPROT:P06400 Protein 53325c52-cb28-11e5-b419-001a4ae51246 11306566 To further test whether inactivation of pRB is linked to abrogation of TNF-α-mediated growth arrest, we tested SV40 large tumor antigen, which can also interact with and inactivate pRB (54). 16 Neoplasms MESH:D009369 activates UNIPROT:P04141 Protein 768c4684-877c-11f0-86f5-0050569a1f61 PMC7138932 29 The blood-nerve barrier is degraded by matrix-metallopeptidase-9 (MMP-9), produced by activated SC and M, and allows influx and efflux of blood factors and cells to facilitate tissue repair in the first 2 weeks.35,36Additionally, tumor necrosis factor-alpha (TNF-α) and IL1α induce fibroblasts to produce IL-6 and granulocyte-macrophage colony-stimulating factor (GM-CSF), which enhance immune cell chemotaxis.35This dynamic secretory sequence of inflammatory cytokines and growth factors rapidly rise and are crucial for M recruitment. 16 Neoplasms MESH:D009369 activates UNIPROT:P01375 Protein 76206d70-cbf1-11e5-a19a-001a4ae51247 10514437 We have investigated the tumor promotion activity of TNF-α in JB6 Cl 41 cells. 16 Neoplasms MESH:D009369 activates UNIPROT:P04637 Protein c1badfd0-ca5d-11e5-9bd2-001a4ae51247 12514185 Because both p53 protein and mRNA levels were approximately equivalent between the normal and tumor p53-transfected cells and proline oxidase mRNA and protein were differentially up-regulated by normal and tumor-derived p53s, we surmised that the tumor-derived p53s were less efficient at transactivating the proline oxidase gene. 16 Neoplasms MESH:D009369 inhibits UNIPROT:P05121 Protein b0d40e4a-cb29-11e5-a6cd-001a4ae51247 11441025 The results of these experiments demonstrated that treatment of mice with this low dose of PAI-1 increased M21 tumor growth by 48% relative to the PBS control (data not shown), a result that exactly mirrors the increase in the growth of tumors treated with partially inactivated PAI-1 (Fig.1). 16 Neoplasms MESH:D009369 activates UNIPROT:P60484 Protein 1effbf3c-37fd-11e6-aaca-001a4ae51246 PMC4463446 Immunohistochemistry analysis showed that paxillin expression levels were significantly inhibited in tumors overexpressing PTEN, when compared with control tumors (Fig. 6B). 16 Neoplasms MESH:D009369 activates UNIPROT:P35869 Protein 0e98285e-052c-11f0-bb39-0050569a791b 10.1016/j.canlet.2024.217076 The presence of KYN in tumors can activate the aryl hydrocarbon receptor (AhR), leading to the release of IL-8 by tumor cells and thereby promoting M2 polarization of macrophages [52]. 16 Neoplasms MESH:D009369 inhibits UNIPROT:P55089 Protein 96053b60-45b4-11f0-afc2-0050569a791b 10.1016/j.biosx.2022.100126 The tumor growth of PDT treated mice was inhibited by injecting UCN directly into melanoma tumors or injecting Ucn combined with tumor targeting agents intravenously into tumor bearing mice.Cohen Research Group (2013)studied the application of aptamer modified MS2 phage capsid in targeted photodynamic therapy in vitro. 16 Neoplasms MESH:D009369 inhibits UNIPROT:Q8N726 Protein b6e9fe0c-3756-11e8-9fbf-001a4a160176 25172038 These findings suggest that ARF-BP1 is a critical regulator of both p53-dependent and p53-independent tumor suppression of ARF. 16 Neoplasms MESH:D009369 inhibits UNIPROT:P40337 Protein a7b067e0-ca5d-11e5-9bd2-001a4ae51247 12538644 It follows then that tumor-derived mutations affecting the surface residues in the β domain effectively abrogate the interaction of pVHL to not only hHIF-1 and -2α subunits but also hHIF-3α1-3 variants. 16 Neoplasms MESH:D009369 activates UNIPROT:Q9NTI5 Protein 6da3ba00-ab8c-11e6-9ac8-001a4ae51246 PMC4646382 The xenograft assay also demonstrated that the tumor growth increased in the 2-month As3+-exposed Nrf2 knockdown BEAS-2B cells. 16 Neoplasms MESH:D009369 phosphorylatesProtein UNIPROT:P40763 Protein 09dced36-1a6c-11f0-aa93-0050569a1f61 10.1016/j.nantod.2024.102521 Recent studies have identified the phenomenon of EML4-ALK fusion and phase separation of EML4-ALK to form condensates in lung cancer tumor tissue regions, which leads to hyperactivation of the MAPK/ERK cell signaling pathway and phosphorylation of the signal transducer and activator of transcription 3 (STAT3), enhancing the ability of the cancer cells to survive and maintain tumor proliferation (Fig. 3b). 16 Neoplasms MESH:D009369 activates UNIPROT:P06703 Protein 466dae36-cb28-11e5-8189-001a4ae51246 11717311 Are tumors overexpressing PR-A more resistant to apoptosis-inducing chemotherapeutic agents or to tamoxifen? 16 Neoplasms MESH:D009369 increases UNIPROT:Q04864 Protein af3d1268-d431-11e6-a821-001a4ae51247 10.1074/jbc.272.35.21774 Late autoregulated transcription is probably indirectly induced following either form of stimulation, as reported for the TcR/CD3-mediated delayed increase in p50 and c-Rel mRNA levels through autocrine secretion of the NF-κB inducer, tumor necrosis factor-α (39,49). 16 Neoplasms MESH:D009369 activates UNIPROT:P05164 Protein 9b2b26ee-4529-11f0-afc2-0050569a791b 10.1016/j.biopha.2022.113158 Moreover, this compound decreased colonic pro-inflammatory mediators, including tumor necrosis factor-alpha, interleukin (IL)− 1 beta, and IL-6, as well as myeloperoxidase activities, and significantly increased the expressions of autophagy-related proteins and promoted the formation of autophagosome in the colon. 16 Neoplasms MESH:D009369 activates UNIPROT:P05019 Protein 544fe610-cb2b-11e5-8189-001a4ae51246 12496288 Patients with IGF-overexpressing tumors tend to have severe hypoglycemia despite low levels of serum insulin (known as non-islet cell tumor hypoglycemia) (26), demonstrating a functional overlap between oncogenic IGFs and insulinin vivo. 16 Neoplasms MESH:D009369 decreases UNIPROT:P04114 Protein 47f7f0f2-cb2a-11e5-a6cd-001a4ae51247 12177061 In contrast to TGF-β, tumor necrosis factor-α has been shown to decrease apoB secretion in both Caco-2 and HepG2 cells (61-63). 16 Neoplasms MESH:D009369 activates UNIPROT:Q53HV7 Protein 47c21b7c-3936-11e8-8f56-001a4a160175 16517288 Administration of diuretics can clear or dilute tracer activity in the ureter, thus confirming physiological uptake rather than metastatic retroperitoneal lymph nodes.19However administration of diuretics requires a delayed acquisition over the “abnormal” region.19Care must be taken when interpreting PET images in the context of renal cell carcinoma as a recent study indicated that only 47% of renal tumors have increased FDG uptake.1This is due to frequent low metabolic activity of renal cell carcinomas. 16 Neoplasms MESH:D009369 activates UNIPROT:P08922 Protein 73cd3524-cb2b-11e5-8189-001a4ae51246 12471025 Of the antioxidant enzymes, only SOD2 is induced by various stimuli, such as tumor necrosis factor-α (34), interleukin-1 (35), and X-irradiation (36) that are known to produce ROS or induce intracellular ROS generation. 16 Neoplasms MESH:D009369 activates UNIPROT:P07858 Protein 7d3a8b46-5e8f-11e6-9b08-001a4ae51246 10.1074/jbc.272.46.29190 Densitometric readings of the 27/28-kDa cathepsin B protein on Western blots of matched pairs showed that tumor-specific increases in cathepsin B mature protein, expressed as A/N or C/N ratios, were significantly higher in intermediate adenomas, late adenomas, and Dukes A cancers compared with Dukes D cancers (p< 0.05,p< 0.04, andp< 0.01, respectively; Wilcoxon rank sum test). 16 Neoplasms MESH:D009369 activates UNIPROT:P04626 Protein 5490e50e-3409-11e8-9fbf-001a4a160176 25813885 The presence of the anti-HER2 Fab’ enhanced thein vitrocytotoxicity of the PE38KDEL-loaded nanoparticles against breast cancer cell lines that overexpress HER2 receptors.In vivo, the immuno-nanoparticles showed an increased anti-tumor activity in tumor-bearing mice over the control immunotoxin (anti-HER2 Fab’ conjugated to the toxin PE38KDEL), and a higher inhibition of the tumor growth, in a tumor xenograft model overexpressing the HER2 receptor, over the control immunotoxin. 16 Neoplasms MESH:D009369 inhibits UNIPROT:Q16570 Protein 0a8126be-bbd3-11e5-9b9d-001a4ae51247 10.1016/j.canlet.2008.04.050 In addition, tumor-associated angiogenesis was reduced in transgenic mice overexpressing murine DARC in endothelial cells[76]. 16 Neoplasms MESH:D009369 activates UNIPROT:Q8IWE4 Protein 5940a3ac-c46f-11e5-9da3-001a4ae51247 PMC4263876 The presence of naturally occurring mutations in human tumors that can abrogate SCCRO3 function supports the role of SCCRO3 as a putative tumor suppressor as well as the requirement of the PONY domain and myristoyl sequence for this activity. 16 Neoplasms MESH:D009369 inhibits UNIPROT:Q8IWE4 Protein 5940a3ac-c46f-11e5-9da3-001a4ae51247 PMC4263876 The presence of naturally occurring mutations in human tumors that can abrogate SCCRO3 function supports the role of SCCRO3 as a putative tumor suppressor as well as the requirement of the PONY domain and myristoyl sequence for this activity. 16 Neoplasms MESH:D009369 activates UNIPROT:O70260 Protein e5662cf4-cb2b-11e5-b419-001a4ae51246 11877452 A low background level of TUNEL-positive cells was seen in Ad/GFP- and PBS-treated tumors with a significant enhancement in the number of TUNEL-positive or apoptotic cells seen in KChAP-overexpressing tumors. 16 Neoplasms MESH:D009369 activates CHEBI:42111 Chemical 10d0e34a-f1a5-11ee-8b99-0050569a1f61 10.1016/S0378-8741(02)00292-1 One hour after the last dose of drug administration solid tumor was induced using DLA cell line in mice as described early. 16 Neoplasms MESH:D009369 activates CHEBI:45296 Chemical 48b691b8-4502-11f0-afc2-0050569a791b 10.1016/j.yacr.2022.04.014 Two of those are already included in the 2021 edition of the WHO Classification of CNS Tumors under the terms of CNS neuroblastoma, FOXR2-activated, and CNS tumor with BCOR internal tandem duplication, but others are emerging, too [41]. 16 Neoplasms MESH:D009369 activates CHEBI:29108 Chemical 14958300-cc24-11e5-b6ad-001a4ae51246 9545257 We repeated the adherent/nonadherent experiment using PMA, the chemokine RANTES (which produces a distinct calcium signal) (21,22), and the tumor promoter thapsigargin, which results in an intracellular calcium signal by blocking the intracellular calcium reuptake mechanism. 16 Neoplasms MESH:D009369 activates CHEBI:37667 Chemical 44f7e4f6-cb8a-11e5-a7a8-001a4ae51246 10807909 We then evaluated the effect of stauroporin (lower panel, lanes 3and4), a potent inhibitor of protein kinases, including CaM kinase, myosin light chain kinase, PKA, PKC, and PKG; genistein (lanes 5and6), a protein-tyrosine kinase inhibitor and thapsigargin (lanes 7and8), a cell permeable tumor promoting sesquiterpene lactone that releases Ca2+by inhibiting endoplasmic reticular Ca2+-ATPase. 16 Neoplasms MESH:D009369 inhibits CHEBI:30106 Chemical 9018a41a-04c5-11f0-8fe6-0050569a1f61 10.1016/j.jddst.2024.105998 The consumption of oxygen by GOx contributes to a hypoxic environment in the tumor which reverses the charge of the azo group, thereby enhancing cellular uptake. 16 Neoplasms MESH:D009369 inhibits MESH:D005978 Phenotype 379a0188-cb29-11e5-8189-001a4ae51246 11279018 To address this issue, intracellular glutathione was reduced either by treatment of small tumor spheroids for 7 days,i.e.from day 5 to day 12 of cell culture with 50 μmBSO, which is an irreversible inhibitor of γ-glutamylcysteine synthetase, the rate-limiting enzyme in glutathione biosynthesis (25) or by incubating tumor spheroids in glutamine-reduced cell culture medium (26). 16 Neoplasms MESH:D009369 activates MESH:D012640 Phenotype 3d6cdff0-f0d6-11ee-9aaa-0050569a1f61 10.1016/S0011-5029(03)00065-8 CT is indicated only if MRI is not available, as when the patient comes to the emergency room with new-onset seizures that are suspected to be caused by intracranial hemorrhage, ischemic stoke, or tumor. 16 Neoplasms MESH:D009369 activates GO:0050817 Phenotype 36939696-00ad-11f0-9c09-0050569a791b 10.1016/j.apjon.2024.100591 Potential causes include significant differences in temperature between the inside and outside of the ice ball during cryoablation leading to ice ball rupture and subsequent vascular or tumor rupture,21cryoablation-induced liver damage causing thrombocytopenia or coagulation factor consumption resulting in coagulation disorders,25bleeding from the ablation needle tract, and puncture damage to the intrahepatic bile ducts. 16 Neoplasms MESH:D009369 activates MESH:D008107 Phenotype 385b8ce0-0503-11f0-bb39-0050569a791b 10.1016/j.compbiomed.2024.108888 For instance, deficiency or loss of NFKB1 promotes chronic liver disease associated with aging, an increase in the ratio of neutrophils to lymphocytes, the development of idiopathic chronic liver disease, and liver cancer characterized by dysplastic nodules, increased tumor incidence, features of steatohepatitis and fibrosis, hepatocellular telomere lesions, and hepatocellular carcinoma[44]. 16 Neoplasms MESH:D009369 activates MESH:D065206 Phenotype 0eeade46-0527-11f0-bb39-0050569a791b 10.1016/j.yexcr.2024.114191 By consuming NETs or inhibiting the formation of NETs through various methods, the tumor invasion and metastasis ability is significantly decreased, which confirms that targeted treatment of NETs can effectively limit tumor metastasis [86]. 16 Neoplasms MESH:D009369 activates GO:0001525 Phenotype d4aba2be-ab9e-11e6-9236-001a4ae51247 PMC4571963 Collectively, these data establish that FGF9 can drive a microvessel maturation program in renal tumors, without stimulating angiogenesis, and that this program entails vessel fortification by pericytes, SMCs, and an enriched basement membrane. 16 Neoplasms MESH:D009369 activates GO:0001525 Phenotype 7a546568-354e-11e8-8f56-001a4a160175 15036262 Thus, NC1 domains might regulate tumor-induced angiogenesis and tumor growth. 16 Neoplasms MESH:D009369 inhibits GO:0001525 Phenotype 0c157d10-cb2b-11e5-8189-001a4ae51246 11782452 The tumor-induced angiogenesis was inhibited by the presence of either chANG (35.5% positive response,p= 0.015) or α2-antiplasmin (40.5% positive response,p= 0.021). 16 Neoplasms MESH:D009369 activates GO:0001525 Phenotype b0d40e4a-cb29-11e5-a6cd-001a4ae51247 11441025 Thus, treatment of tumors with low doses of PAI-1 can stimulate tumor growth most likely by stimulating angiogenesis. 16 Neoplasms MESH:D009369 activates GO:0001525 Phenotype c1f9d680-1c25-11f0-b759-0050569a791b 10.1016/j.biopha.2023.116058 TAMs are a group of multi-faceted functional immune cells that can differentiate along two trajectories, the M1 and M2 phenotypes, with the former presenting tumor suppression function and the latter promoting tumor proliferation, invasion, metastasis and angiogenesis[44]. 16 Neoplasms MESH:D009369 inhibits MESH:D006863 Phenotype 75a6f19a-4557-11f0-86f5-0050569a1f61 10.1016/j.ijpharm.2022.121791 In addition, the lack of lymphatic drainage in tumors causes the lactate product to remain in the tumor microenvironment and decrease local pH to around 6.5 to 6.8 (Feng et al., 2018). 16 Neoplasms MESH:D009369 inhibits MESH:D005990 Phenotype a2d6be66-45a7-11f0-9ac3-0050569a1f61 10.1016/j.jconrel.2022.03.043 Small nanoparticles demonstrated a ~3-fold enhanced accumulation in tumors via DC101-mediated IFP reduction and the reestablishment of convection delivery, while there was no significant improvement in the penetration for large nanoparticles. 16 Neoplasms MESH:D009369 activates GO:0006955 Phenotype a7d723fc-3c78-11f0-afc2-0050569a791b 10.1016/j.nantod.2022.101512 Cheng et al. utilize genetic engineering and “Plug-and-Display” technology to construct a flexible tumor vaccine platform based on OMVs for rapid display of the target antigens, this tumor vaccine can realize the synergistic treatment of innate immunity and adaptive immunity, and elicited antigen-specific immunity against a variety of tumors in vivo (Fig. 10a-d)[171]. 16 Neoplasms MESH:D009369 activates GO:0006955 Phenotype 32c88fc2-1c1d-11f0-bb75-0050569a1f61 10.1016/j.jconrel.2023.12.023 Moreover, the combined treatment group of DAC + LipoDPP showed strong tumor inhibition abilities.In vitroandin vivostudies have shown that, compared with inducing tumor cell immunogenic apoptosis, induced tumor immunogenic pyroptosis can produce a stronger anti-tumor immune response and the formation of immune memory. 16 Neoplasms MESH:D009369 activates MESH:D002395 Phenotype 47193630-3777-11e8-8636-001a4a160175 15708293 It is the principal cause of morbidity in affected patients and usually the earliest manifestation, often presenting as a neck mass or persistent diarrhea.162Medullary thyroid carcinoma is especially aggressive in patients with MEN2B prone to early metastasis.163 Pheochromocytomas, catecholamine-producing tumors of the adrenal medulla, occur in about one half of patients with MEN2,152typically after the detection of medullary thyroid carcinoma by several years.164Although pheochromocytomas are rarely malignant (<5%),165they can cause inappropriate sympathetic stimulation (intractable hypertension, tachycardia) through secretion of epinephrine and norepinephrine. 16 Neoplasms MESH:D009369 activates GO:0008283 Phenotype 0f166e18-cb8d-11e5-a7a8-001a4ae51246 10636838 HGF/NK4 potently inhibits tumor growthin vivoby increasing tumor cell apoptosis without affecting the proliferation rate of tumor cells (15). 16 Neoplasms MESH:D009369 inhibits GO:0008283 Phenotype 5282a1f6-0528-11f0-bb39-0050569a791b 10.1016/j.cej.2024.152703 In the acidic tumor environment, the pH-responsive GG/GO/Cur scaffold displayed anti-tumor actions by eliminating tumor cells and inhibiting their proliferation through curcumin production. 16 Neoplasms MESH:D009369 activates GO:0008283 Phenotype fe7c60ee-cc27-11e5-aade-001a4ae51247 9525916 IL-1 and tumor necrosis factor-α stimulate proliferation of astrocytes (63-65) and can counteract growth-promoting effects of other cytokines and inhibit the proliferation of human glioblastoma cells (61,66,67). 16 Neoplasms MESH:D009369 activates GO:0008283 Phenotype c1f9d680-1c25-11f0-b759-0050569a791b 10.1016/j.biopha.2023.116058 TAMs are a group of multi-faceted functional immune cells that can differentiate along two trajectories, the M1 and M2 phenotypes, with the former presenting tumor suppression function and the latter promoting tumor proliferation, invasion, metastasis and angiogenesis[44]. 16 Neoplasms MESH:D009369 activates MESH:D013921 Phenotype 36939696-00ad-11f0-9c09-0050569a791b 10.1016/j.apjon.2024.100591 Potential causes include significant differences in temperature between the inside and outside of the ice ball during cryoablation leading to ice ball rupture and subsequent vascular or tumor rupture,21cryoablation-induced liver damage causing thrombocytopenia or coagulation factor consumption resulting in coagulation disorders,25bleeding from the ablation needle tract, and puncture damage to the intrahepatic bile ducts. 16 Neoplasms MESH:D009369 decreases MESH:D010100 Phenotype 6695ef4e-1a5f-11f0-aa93-0050569a1f61 10.1016/j.jddst.2024.106320 Additionally, the PDT efficiency in tumors is limited due to low oxygen levels (hypoxic microenvironment). 16 Neoplasms MESH:D009369 activates MESH:D010100 Phenotype fe24b670-1ba8-11f0-b759-0050569a791b 10.1016/j.cej.2024.150067 The effect of tumor photodynamic therapy can be enhanced by improving energy conversion efficiency and tumor oxygen content. 16 Neoplasms MESH:D009369 inhibits GO:0051179 Phenotype 1967e2fc-cbf1-11e5-b7d4-001a4ae51246 10601287 In contrast, the inhibitor of tumor promotion 12-deoxyphorbol 13-phenylacetate (1 μm) predominantly induced nuclear membrane localization with little plasma membrane localization. 16 Neoplasms MESH:D009369 activates GO:0090195 Phenotype c60c87e2-352b-11e8-87fd-001a4a160176 27846389 Interestingly, the lung epithelial cell TLR3 can be activated by tumor exosomal RNAs to induce chemokine secretion in the lung, consequently recruiting neutrophils to the lung for pre-metastatic niche formation and promoting lung metastasis (Liu et al., 2016). 16 Neoplasms MESH:D009369 inhibits GO:0030431 Phenotype ac78e2f8-cb29-11e5-b419-001a4ae51246 11447223 However, on top of the microenvironments, Ang-2, not Ang-1, produced by the predominant primary tumors, which is stable and has a long half-life (data not shown), could travel to the distant organs and change the balance in favor of inhibiting tumor angiogenesis, which may contribute to the dormancy observed in some secondary tumors. 16 Neoplasms MESH:D009369 activates MESH:D009362 Phenotype c1f9d680-1c25-11f0-b759-0050569a791b 10.1016/j.biopha.2023.116058 TAMs are a group of multi-faceted functional immune cells that can differentiate along two trajectories, the M1 and M2 phenotypes, with the former presenting tumor suppression function and the latter promoting tumor proliferation, invasion, metastasis and angiogenesis[44]. 16 Neoplasms MESH:D009369 inhibits MESH:D009362 Phenotype 6f4cba1e-3745-11e8-a51f-001a4a160176 26687632 Spontaneous tumor regression exemplifies the capacity of the immune system to eradicate tumors and inhibit metastasis. 16 Neoplasms MESH:D009369 activates MESH:D009362 Phenotype c60c87e2-352b-11e8-87fd-001a4a160176 27846389 Interestingly, the lung epithelial cell TLR3 can be activated by tumor exosomal RNAs to induce chemokine secretion in the lung, consequently recruiting neutrophils to the lung for pre-metastatic niche formation and promoting lung metastasis (Liu et al., 2016). 16 Neoplasms MESH:D009369 activates MESH:D009361 Phenotype c1f9d680-1c25-11f0-b759-0050569a791b 10.1016/j.biopha.2023.116058 TAMs are a group of multi-faceted functional immune cells that can differentiate along two trajectories, the M1 and M2 phenotypes, with the former presenting tumor suppression function and the latter promoting tumor proliferation, invasion, metastasis and angiogenesis[44]. 16 Neoplasms MESH:D009369 activates MESH:D009361 Phenotype 1929de28-3777-11e8-8636-001a4a160175 15797292 These abnormalities are generally connected to the tumor via the spicules, but only histologic examination will enable determination of their invasion by the tumor. 16 Neoplasms MESH:D009369 activates MESH:D009361 Phenotype d682418e-352b-11e8-87fd-001a4a160176 PMC5546617 The tumor usually causes vascular invasion and pancreatic ductal obstruction at an early stage and thus is well depicted on cross-sectional imaging; however, a more cystic appearance may be seen. 16 Neoplasms MESH:D009369 inhibits GO:0007155 Phenotype 0d1fa568-4566-11f0-9ac3-0050569a1f61 10.1016/j.jconrel.2022.04.039 CL4 was also shown to strongly inhibit tube formation and tumor growth by impairing matrix-induced integrin αvβ3 interactions with EGFR and integrin αvβ3-dependent cell adhesion in a xenograft triple-negative breast cancer model [166]. 16 Neoplasms MESH:D009369 activates MESH:D001943 Phenotype 1bc5dd50-3531-11e8-9fbf-001a4a160176 24637217 Tumor latency and tumor progression Prophylactic activity of free CoQ10 and CoQ10-LCNPs was established in female Sprague Dawley rats employing 7,12-dimethylbenz[α]anthracene (DMBA) induced breast tumor model following protocol established in our laboratory.23,27,34Briefly, the animals were randomly divided in different groups (n=6) and prophylactically treated with formulations as per Table S1 (see supplementary information). 16 Neoplasms MESH:D009369 activates GO:0000422 Phenotype 537caebc-0550-11f0-bb39-0050569a791b 10.1016/j.bbamcr.2024.119752 Furthermore, fission-induced mitophagy, operating independently of parkin, selectively elevated the presence of CD81+/PD-L1+ extracellular vesicles in the tumor interstitial fluid of an in vivo breast cancer model, emphasizing mitophagy's potential contribution to immunosuppression [201]. 16 Neoplasms MESH:D009369 activates GO:0030154 Phenotype de9c499a-1a5d-11f0-85c3-0050569a1f61 10.1016/j.lfs.2024.123174 Glioblastoma releases several microRNAs or oligodendrocyte transcription factors around the tumor border, which increases the differentiation of OPCs into oligodendrocytes, resulting in enhanced stemness of glioblastoma and the tumor growth [53,54]. 16 Neoplasms MESH:D009369 inhibits MESH:D051379 Phenotype 19143ea8-5cba-11e7-b441-001a4ae51247 PMC4706013 The tumor growth was accompanied by the substantial formation of new blood vessels around the dorsal subcutaneous tumor in wild-type mice, but tumor-associated angiogenesis was attenuated inmPges1−/−mice (Fig. 1C). 16 Neoplasms MESH:D009369 activates MESH:D051379 Phenotype 10d0e34a-f1a5-11ee-8b99-0050569a1f61 10.1016/S0378-8741(02)00292-1 One hour after the last dose of drug administration solid tumor was induced using DLA cell line in mice as described early. 16 Neoplasms MESH:D009369 inhibits GO:0006915 Phenotype c12f03e8-cb2a-11e5-9aa0-001a4ae51247 11943780 Other studies suggest that p53 and Siah1 share a common mechanism of tumor suppression and induction of apoptosis that involves protein folding, unfolding, and trafficking (37). 16 Neoplasms MESH:D009369 activates GO:0006915 Phenotype ce81be82-cb2a-11e5-b419-001a4ae51246 11940602 Note that tumor lines such as prostate cancer PPC-1, ovarian cancer OCVAR-3, and cervical cancer HeLa are triggered by the combination of PPARγ modulators and TRAIL to undergo apoptosis (Fig.2,AandB), activate caspases (Fig.2C), and cleave the caspase substrate PARP (Fig.2D). 16 Neoplasms MESH:D009369 inhibits GO:0006915 Phenotype b2547b56-0021-11f0-8027-0050569a1f61 10.1016/j.prp.2025.155815 Matsushita et al.[69]reported the tumor suppressant activity of miR-145–5p or (miR-145–3p) on the viability of UBC cells and increased apoptosis. 16 Neoplasms MESH:D009369 activates GO:0006915 Phenotype 0f166e18-cb8d-11e5-a7a8-001a4ae51246 10636838 HGF/NK4 potently inhibits tumor growthin vivoby increasing tumor cell apoptosis without affecting the proliferation rate of tumor cells (15). 16 Neoplasms MESH:D009369 activates GO:0006915 Phenotype b5fa0358-cb8c-11e5-9498-001a4ae51246 11092892 This suggests that mitochondrial oxidative damage plays an important role in hydrogen peroxide-induced apoptosis but is not required for apoptosis induced by staurosporine or tumor necrosis factor-α. 16 Neoplasms MESH:D009369 activates GO:0006915 Phenotype 3e6ec5fc-a1a7-11e6-9b40-001a4ae51246 10.1074/jbc.273.43.27816 The substitution of Lys709to arginine makes ASK1 dominant negative; this mutant can prevent both activation of JNK and apoptosis induced by tumor necrosis factor-α and actinomycin D in lung epithelial cells (14). 16 Neoplasms MESH:D009369 activates GO:0006915 Phenotype 81d0bc9a-3f98-11e6-b1b0-001a4ae51247 17409807 They are secreted, soluble members of the semaphorin family, important in axonal guidance.129,130Wild-type SEMA3B, but not tumor-acquired single–amino acid missense mutants of SEMA3B, induces apoptosis when reexpressed in lung cancers or added as soluble molecules.131,132One mechanism of such tumor inhibition is through its ability to block VEGF autocrine activity.131The growth-inhibitory effects of SEMA3F are also observed in rat xenografts of NSCLC.133Because both SEMA3B and SEMA3F are soluble, secreted proteins, they are promising candidates as drugs for systemic treatment. 16 Neoplasms MESH:D009369 activates GO:0006915 Phenotype 45ca1672-1fab-11e6-a85d-001a4ae51246 10.1074/jbc.273.28.17926 It should be noted that the DU145 cell line is resistant to apoptosis induced by Fas and tumor necrosis factor-α (23). 16 Neoplasms MESH:D009369 activates GO:0008219 Phenotype 53cff1c2-004a-11f0-9c09-0050569a791b 10.1016/j.colsurfb.2024.114375 Importantly, CA-AuAgNPs-Gel induced tumor apoptosis via photothermal-induced hyperthermia and immunogenic cell death under NIR laser radiation. 16 Neoplasms MESH:D009369 inhibits MESH:D003643 Phenotype 0be5437a-392e-11e8-9fbf-001a4a160176 9063588 An additional study revealed that laparotomy enhances death from pancreatic tumors by decreasing latency of primary footpad tumors and enhances the incidence of tumor metastases[484]. 16 Neoplasms MESH:D009369 activates MESH:D003643 Phenotype 6a6e6da6-0d5f-11f0-bb75-0050569a1f61 10.1182/blood.V93.12.4071 The criteria for tumor-induced death were defined as either hepatosplenomegaly with macroscopic tumor nodules in liver and/or spleen or evidence of spinal cord involvement (hind leg paralysis or pathological demonstration of p815 tumor cells in the spinal cord). 16 Neoplasms MESH:D009369 inhibits GO:0006954 Phenotype 15566f32-867f-11f0-8cae-0050569a1f61 10.1016/j.scitotenv.2020.143872 When transported to distant tissues, MPs might cause chronic inflammation, decreased organ function, and an increased risk of neoplasm (Prata et al., 2020). 16 Neoplasms MESH:D009369 activates MESH:D003094 Phenotype 7026da42-5c75-11e7-bcb7-001a4ae51246 PMC6186419 Of note, in vivo studies have demonstrated that BRAF inhibitors not only act in melanoma cells but also in the surrounding tumor fibroblasts, activating them to produce a stiff, collagen-rich ECM (Hirata et al., 2015). 16 Neoplasms MESH:D009369 activates MESH:D012507 Phenotype ffaf1006-3403-11e8-bf76-001a4a160175 26478443 Anti-tumor necrosis factor-α agents Macrophage produced tumor necrosis factor-α (TNF-α) drives the inflammatory process in sarcoidosis (Ziegenhagen et al., 2002). 16 Neoplasms MESH:D009369 activates GO:1903409 Phenotype 73cd3524-cb2b-11e5-8189-001a4ae51246 12471025 Of the antioxidant enzymes, only SOD2 is induced by various stimuli, such as tumor necrosis factor-α (34), interleukin-1 (35), and X-irradiation (36) that are known to produce ROS or induce intracellular ROS generation. 16 Neoplasms MESH:D009369 activates GO:0001503 Phenotype 8118cb7e-3403-11e8-a51f-001a4a160176 26916298 Kerr et al. demonstrated, in three mouse models of tumor-induced bone formation, that platelets have a role in governing pre-metastatic tumor communication[112]. 16 Neoplasms MESH:D009369 activates MESH:D010146 Phenotype b1b00c90-341a-11e8-9fbf-001a4a160176 17398221 Other causes of peripheral neuropathy in older adults include alcoholic polyneuropathy, chemotherapy-induced polyneuropathy, entrapment neuropathies, postmastectomy pain, post-thoracotomy pain, nerve compression or infiltration by tumor, phantom limb pain, postradiation plexopathy, and trigeminal neuralgia.17Central poststroke pain may also present with symptoms that mimic peripheral neuropathy. 16 Neoplasms MESH:D009369 activates MESH:D010778 Phenotype 6695ef4e-1a5f-11f0-aa93-0050569a1f61 10.1016/j.jddst.2024.106320 Conventional PSs including chlorin, porphyrin, BODIPY, and phthalocyanine compounds have low water solubility and limited tumor specificity, which reduce the effectiveness of PDT. 16 Neoplasms MESH:D009369 inhibits MESH:D002100 Phenotype 8c07cf66-c46c-11e5-91a7-001a4ae51247 PMC4069240 The University of Graz (Austria) offers ATGL inhibitors with various structures for treatment of type 2 diabetes and tumor-induced cachexia by way of ATGL and HSL inhibition[248]. 16 Neoplasms MESH:D009369 inhibits GO:0006914 Phenotype 551c7fc2-37fa-11e6-8a17-001a4ae51247 PMC4505457 These initial results suggested a correlation between DAXX expression and decreased autophagy, becauseDAXXK/D tumors displayed elevated autophagy, as evidenced by decreased p62 in autophagy-intact PCa cells (PC3). 16 Neoplasms MESH:D009369 activates GO:0002118 Phenotype 9944a3f0-bc44-11e5-9b9d-001a4ae51247 PMC2742305 Several macrophage and tumor-derived molecules are implicated in the macrophage-induced tumor aggression of which Wnt 5a is an example. 16 Neoplasms MESH:D009369 inhibits GO:0042098 Phenotype b6f9f49e-351a-11e8-a51f-001a4a160176 28647610 Tumor-associated MDSCs derived from patients with head and neck squamous cell carcinoma express higher levels of pSTAT3 and rely on STAT3 to suppress T cell proliferation through the actions of arginase 1[67]. 16 Neoplasms MESH:D009369 activates GO:0006096 Phenotype faf8a9fe-5caf-11e7-8c5f-001a4ae51246 PMC4676726 Indeed, one of the first characterized effects of the proto-oncogenic tyrosine kinase SRC was inactivation of purified chicken-liver pyruvate kinase M2 in tumor lysates (Glossmann et al., 1981), leading to the hypothesis that SRC regulates glycolysis. 16 Neoplasms MESH:D009369 activates MESH:D005334 Phenotype 53cff1c2-004a-11f0-9c09-0050569a791b 10.1016/j.colsurfb.2024.114375 Importantly, CA-AuAgNPs-Gel induced tumor apoptosis via photothermal-induced hyperthermia and immunogenic cell death under NIR laser radiation. 16 Neoplasms MESH:D009369 activates PF:PF08260 ProteinFamily a2d6be66-45a7-11f0-9ac3-0050569a1f61 10.1016/j.jconrel.2022.03.043 Notably, various types of tumors overexpress kinin receptors and have high levels of BK [147], thus resulting in high permeability of tumor vasculature. 16 Neoplasms MESH:D009369 inhibits FPLX:PPP2 ProteinFamily 3d8436d0-cb2a-11e5-a6cd-001a4ae51247 12191994 In this scenario, Bγ would act similarly to DNA tumor virus antigens that inhibit PP2A by displacing cellular regulatory subunits. 16 Neoplasms MESH:D009369 increases FPLX:VEGF ProteinFamily 3553d88c-f0ea-11ee-9aaa-0050569a1f61 10.1016/S1040-8428(03)00067-2 Invasive tumors overexpress TP, HGF, and midline, while VEGF is overexpressed by superficial tumors[67]. 16 Neoplasms MESH:D009369 decreases FPLX:VEGF ProteinFamily de8f2152-bc43-11e5-8abe-001a4ae51246 10.1016/j.cytogfr.2005.01.005 For example, the related tumor suppressors p53 and p73 inhibit VEGF expression in tumor cell lines through the same general region of the VEGF promoter[117,118], whereas mutant p53 has been shown to potentiate PKC induction of VEGF expression in the same system[117]. 16 Neoplasms MESH:D009369 inhibits FPLX:PPP3 ProteinFamily e7dbbf10-d6b8-11e5-8cf6-001a4ae51246 9867815 Notably, both tumor necrosis factor-α (50 ng/ml) and interferon-γ (50 units/ml) elicited an inhibition of CN activity of about 25% after 2 h of treatment. 16 Neoplasms MESH:D009369 activates FPLX:Integrins ProteinFamily e133c0c8-3529-11e8-87fd-001a4a160176 25308250 The fact that both the cRGD- and cRAD-targeted BCMs were the same size (i.e.approximately 30nm) suggests that a phenomenon distinct from, or additive to, the EPR effect may be at play, enabling the specific binding and uptake of cRGD-targeted BCMs in angiogenic tumors overexpressing integrin receptors. 16 Neoplasms MESH:D009369 activates FPLX:Actin ProteinFamily 28377836-3804-11e6-8a17-001a4ae51247 PMC4409274 Western blotting revealed that the presence of LLC tumors increased the 14-kDa actin fragment in muscles of control and C/EBPδ KO mice (Fig. 4H). 16 Neoplasms MESH:D009369 activates FPLX:Fibrin ProteinFamily c60c87e2-352b-11e8-87fd-001a4a160176 27846389 CD11b+CD68+F4/80+myeloid cells are recruited to the lung by primary tumor-induced fibrin clots before the metastatic tumor cells arrive at the distant organ, promoting niche formation and breast cancer metastasis (Gil-Bernabe et al., 2012). 16 Neoplasms MESH:D009369 decreases FPLX:COX ProteinFamily ae658742-aba2-11e6-9236-001a4ae51247 PMC4571870 However, 20 tumor samples had decreased expression (below 0.2-fold) of the complex IV subunit, implying mitochondrial defects. 16 Neoplasms MESH:D009369 activates FPLX:AKT ProteinFamily dc026662-cb8c-11e5-8106-001a4ae51247 10770919 RhoB-F was just as potent as RhoB-GG at inhibiting human tumor growthin vitroand IGF-1 stimulation of Akt and constitutive activation of Erk2 as well as inducing apoptosis and inhibiting tumor growth in nude mice. 16 Neoplasms MESH:D009369 activates UNIPROT:P09038 Protein f54b9f8e-354e-11e8-b868-001a4a160176 17645940 Egr-1 Transient induction of the transcription factor Egr-1 plays a pivotal role in the transcriptional response of endothelial cells to the angiogenic growth factors VEGF and basic fibroblast growth factor (bFGF), which are produced by most tumors and are involved in angiogenesis.|||Transient induction of the transcription factor Egr-1 plays a pivotal role in the transcriptional response of endothelial cells to the angiogenic growth factors VEGF and basic fibroblast growth factor (bFGF), which are produced by most tumors and are involved in angiogenesis. 16 Neoplasms MESH:D009369 activates UNIPROT:P01241 Protein a5138fe4-1b2a-11f0-b759-0050569a791b 10.1016/j.beem.2024.101893 It has emerged as the most extensively studied molecular marker for SRLs response as numerous studies have shown that elevated levels of SSTR2 protein in GH-producing tumors are associated, both in vivo and in vitro, with the effectiveness of fg-SRLs treatment[69–73].|||Nevertheless, there are additional challenges in establishing a consistent routine immunohistochemistry assessment for SSTRs in GH-producing tumors such as the absence of consensus on a uniform IHC scoring method and approach, the variability in SSTR expression across various tumor samples, and numerous potential confounding factors, including prior SRLs treatment that could change SSTR expression. 16 CHEBI:7421 inhibits Neoplasms MESH:D009369 Chemical 47e15ac0-3943-11e8-87fd-001a4a160176 15385082 In fact, NAC significantly reduced tumor incidence in the DSS mice as well as the tumor multiplicity. 16 UNIPROT:P05362 activates Neoplasms MESH:D009369 Protein bc6892f2-3c72-11f0-afc2-0050569a791b 10.1016/j.addr.2022.114365 M2a macrophages were observed to infiltrate and release tumor cells from cell aggregates, indicating that ICAM-1 and integrin β2 interactions could induce tumor dissemination by contact. 16 MESH:D005354 activates Neoplasms MESH:D009369 Phenotype 48456cd0-cbf0-11e5-b0dd-001a4ae51247 10224095 Intravenous injection of CLDC containing the p53, angiostatin, or GM-CSF genes reduced tumor angiogenesis by levels comparable with the reduction in tumor angiogenesis produced by the implantation of a murine T241 fibrosarcoma cell line stably transfected with the murine angiostatin gene (24). 16 MESH:D008748 activates Neoplasms MESH:D009369 Phenotype 9944a3f0-bc44-11e5-9b9d-001a4ae51247 PMC2742305 In contrast, MCA-induced tumors that emerged in the wild-type mice were never rejected on transplantation suggesting that lymphocytes shape immunogenicity, and hence immunoedit the tumor. 16 UNIPROTPRO:PRO:0000005794 inhibits Neoplasms MESH:D009369 Protein 6c03282c-cb2a-11e5-8189-001a4ae51246 12435733 Because endostatin inhibits endothelial cell proliferation and effectively arrests the growth of several tumors (44), and because perlecan and endostatin co-localize in most basement membranes (2,3,45,46), we reasoned that an interaction between these two proteins could occurin vivoand could play a role in tumor progression. 16 UNIPROTPRO:PRO:0000005794 inhibits Neoplasms MESH:D009369 Protein 4c6d21fc-341e-11e8-9192-001a4a160175 11172729 Endostatin specifically suppresses endothelial cell proliferationin vitroand increases the apoptotic rate in tumors 7-fold without affecting the proliferation rate of the tumor cells.In vivo, endostatin showed potent inhibitory activity against EOMA, Lewis lung, T241 fibrosarcoma, and B16F10 tumor cell lines. 16 UNIPROT:P08865 activates Neoplasms MESH:D009369 Protein 1c676042-cb2c-11e5-b419-001a4ae51246 12376527 100 ng/ml TPA treatment of cells has been reported previously to induce ectodomain shedding of APP, erbB4, and LRP by activating tumor necrosis factor-α converting enzyme (TACE) or other metalloproteases (19,22,25). 16 UNIPROT:P08865 inhibits Neoplasms MESH:D009369 Protein 7da8e326-cc99-11e5-888a-001a4ae51246 PMC4003901 1, aspirin and SA inhibit tumor promotor (TPA)-induced transformation in a concentration-dependent manner. 16 MESH:D013629 activates Neoplasms MESH:D009369 Phenotype b010e33a-cb28-11e5-9aa0-001a4ae51247 11553641 Wolfet al.reported a naturally occurring amino acid substitution at position 351 in ERα (ERα(D351Y)) derived from a tamoxifen-stimulated tumor (Fig.5A) (68,69). 16 UNIPROT:Q13485 inhibits Neoplasms MESH:D009369 Protein f58fdb52-c46e-11e5-a92e-001a4ae51246 PMC4246091 Indeed, tumor growth and invasion in Min mice is accelerated by loss of Smad2 or Smad4 (7,8). 16 UNIPROT:P22681 inhibits Neoplasms MESH:D009369 Protein 677d41ba-cb8a-11e5-a7a8-001a4ae51246 10940298 Thus, in combination with the biochemical data we presented, the inverse relationship between c-Cbl expression and tumor size suggests that overexpression of c-Cbl can inhibit tumor growth driven by theneuoncogene. 16 MESH:D014815 inhibits Neoplasms MESH:D009369 Phenotype 20d7fe00-cbf1-11e5-a19a-001a4ae51247 10585423 Our laboratory has reported, in fact, that a synthetic fluorinated vitamin D3analog, F6-D3, significantly reduced the tumor incidence in the azoxymethane model of rat colonic tumorigenesis (37). 16 UNIPROT:Q99683 activates Neoplasms MESH:D009369 Protein 3e6ec5fc-a1a7-11e6-9b40-001a4ae51246 10.1074/jbc.273.43.27816 Dominant negative ASK1(K709R) inhibited ASK1 activation induced by Gα12, Gα13, and tumor necrosis factor-α (Fig.3). 16 CHEBI:59585 inhibits Neoplasms MESH:D009369 Chemical 1858c23a-3749-11e8-a34b-001a4a160175 26432555 Moreover, liposomal clodronate also efficiently depleted phagocytic cells and inhibited tumor growth in the murine tetratocarcinoma (F9) and human rhabdomyosarcoma (A673) xenografts in mice. 16 UNIPROT:Q13309 activates Neoplasms MESH:D009369 Protein 1e2fdd40-04bc-11f0-9c9e-0050569a1f61 10.1016/j.biopha.2024.117356 Mechanistically, FKA interrupted the ATP-binding pocket in NAE to prevent NEDD8 conjugation to UBE2M and CUL-1, thus triggering the ubiquitylation and degradation of S-phase kinase-associated protein 2 (SKP2) to cause the accumulation of tumor suppressive protein p27[83]. 16 UNIPROT:Q03001 activates Neoplasms MESH:D009369 Protein ffd3a04a-390a-11e8-8f56-001a4a160175 25437110 Briefly, colon neoplasia was induced by a weekly subcutaneous injection of 100μl of DMH (4mg/100g rat body weight), for 5 weeks, after which the rats were kept for an additional 10 weeks, under daily inspection. 16 MESH:D004656 activates Neoplasms MESH:D009369 Phenotype a2d6be66-45a7-11f0-9ac3-0050569a1f61 10.1016/j.jconrel.2022.03.043 Orally administered enalapril augmented EPR-mediated bacteria accumulation in tumor tissues by 6–18-fold in both tumor models as compared to non-enalapril treated controls, likely because ACEi induced vessel dilation and enlarged endothelial gaps. 16 UNIPROT:O00418 inhibits Neoplasms MESH:D009369 Protein a6029332-390a-11e8-9192-001a4a160175 25464034 Overexpression of eEF2K prevents caloric restriction-induced tumor necrosis in tumor xenografts[105], and AMPK overactivation enhances tumor growth in immunocompromised mice[133]. 16 UNIPROT:P0C0P6 activates Neoplasms MESH:D009369 Protein b9629eda-390b-11e8-bf76-001a4a160175 25447422 The paclitaxel-loaded PEO-PbAE NPs induced 5.2-fold higher tumor accumulation of paclitaxel and enhanced tumor regression in SKOV-3 xenograft model when compared to paclitaxel in solution. 16 UNIPROT:Q86WV6 inhibits Neoplasms MESH:D009369 Protein d032fe7a-0019-11f0-9c09-0050569a791b 10.1016/j.intimp.2025.114013 The combined use of OXA liposomes and STING agonists reduces tumor growth potential by modulating the immune suppressive state of tumors, providing more effective and targeted methods for cancer treatment. 16 MESH:D065206 activates Neoplasms MESH:D009369 Phenotype 0eeade46-0527-11f0-bb39-0050569a791b 10.1016/j.yexcr.2024.114191 NETs promote tumor growth NETs cause malignant tumor progression by promoting tumor cell proliferation. 16 CHEBI:46726 inhibits Neoplasms MESH:D009369 Chemical e17ecdb4-1cb4-11f0-bb75-0050569a1f61 10.1016/j.ntm.2023.100022 Compared with the monotherapy group, the anti-tumor immune response of the magnetite cationic liposome-mediated PT and IL-2 and granulocyte-macrophage colony-stimulating factor combination therapy group was significantly enhanced, which greatly reduced the tumor burden and increased the survival rate. 16 CHEBI:4806 activates Neoplasms MESH:D009369 Chemical 3bc85b44-c46f-11e5-8491-001a4ae51247 PMC4239619 Furthermore, EGCG also induced PP2A activation on tumors (Fig. 1M). 16 CHEBI:4806 inhibits Neoplasms MESH:D009369 Chemical 486bea0c-0027-11f0-a3d5-0050569a1f61 10.1016/j.envint.2025.109299 EGCG inhibits methyltrienolone-induced prostate tumor growth in mice by downregulating miR-21-5p (Siddiqui et al. 2011). 16 CHEBI:17877 inhibits Neoplasms MESH:D009369 Chemical b75315a4-1b9c-11f0-b40b-0050569a1f61 10.1016/j.biopha.2024.116386 Brequinar, a DHODH inhibitor, selectively inhibits the growth of GPX4-low tumors by inducing ferroptosis, whereas brequinar combined with sulfasalazine, an FDA-approved medication with ferroptosis-inducing activity, synergistically induces ferroptosis and inhibits the growth of GPX4-high tumors[90]. 16 MESH:D000077332 inhibits Neoplasms MESH:D009369 Phenotype baf56a38-3510-11e8-a34b-001a4a160175 26651127 Recent studies reported that Artesunate and its derivatives can inhibit tumor angiogenesis by inducing vascular endothelial cells apoptosis. 16 MESH:D003609 activates Neoplasms MESH:D009369 Phenotype 4ebb8342-cbf0-11e5-a19a-001a4ae51247 10347161 Actinomycin D and α-amanitin have both been shown to promote an increase in tumor necrosis factor-α mRNA (55). 16 FPLX:Ubiquitin activates Neoplasms MESH:D009369 ProteinFamily 1a059788-1c1c-11f0-b759-0050569a791b 10.1016/j.ebiom.2024.104972 In which GNA could covalently join the EZH2 SET domain in a covalent way and significantly suppress tumor development by degrading EZH2.52 E3 ligases Von Hippel-Lindau (VHL) and cereblon (CRBN) proteins are the two most common ubiquitin enzymes in biology. 16 UNIPROT:P35354 activates Neoplasms MESH:D009369 Protein f8f0cfee-1a55-11f0-b40b-0050569a1f61 10.1016/j.jddst.2024.106376 Cyclooxygenase-2 (COX-2), which is highly expressed in a variety of cancers and serves as an indicator for inflammation evaluation, can be targeted by aspirin to modulate tumor-associated inflammation. 16 UNIPROT:P35354 activates Neoplasms MESH:D009369 Protein 7e44a6f4-cb2b-11e5-9aa0-001a4ae51247 12080072 Consistently, (i) arachidonic acid stimulates the growth of prostate cancer cells (28), possibly through overproduction of 5- and 15-LOX metabolites acting as anti-apoptotic autocrine factors (45); and (ii) COX-2 is specifically up-regulated in a variety of cancer cells (40,46-50), and causes mammary tumors when overexpressed under the control of the murine mammary tumor virus promoter (51). 16 UNIPROT:P35354 activates Neoplasms MESH:D009369 Protein ae1aefc6-ca01-11e5-9b70-001a4ae51247 15855163 Given that COX-2-derived prostaglandins mediate effects primarily through specific plasma membrane receptors that are coupled with G-proteins and that certain GPCRs are known to activate EGFR (24-26), we postulated that COX-2 may promote tumor growth through activation of EGFR. 16 UNIPROT:P09038 inhibits Neoplasms MESH:D009369 Protein 3553d88c-f0ea-11ee-9aaa-0050569a1f61 10.1016/S1040-8428(03)00067-2 Treatment with paclitaxel and cetuximab downregulated the expression of VEGF, bFGF, IL-8, and MMP-9 and inhibited tumor-induced neovascularity compared with untreated controls. 16 CHEBI:24996 activates Neoplasms MESH:D009369 Chemical bdeca110-1b7d-11f0-b759-0050569a791b 10.1016/j.canlet.2024.216837 Taken together, lactate-mediated impacts on tumor cell proliferation, PCD inhibition, EMT, angiogenesis, drug resistance and TME remodeling greatly promote tumor progression and metastasis via various mechanisms (Fig. 3). 16 MESH:D006863 activates Neoplasms MESH:D009369 Phenotype 9d305ba0-351c-11e8-bf76-001a4a160175 28525855 Together, PMNs are excellent pH-responsive theranostic agents that enable the early diagnosis of tumors and superior therapeutic efficacy in highly heterogeneous drug-resistant tumors. 16 MESH:D006863 activates Neoplasms MESH:D009369 Phenotype 2c5e01aa-04dd-11f0-bb39-0050569a791b 10.1016/j.bcp.2024.116254 Furthermore, low pH contributes to create a tumor-promoting TME by participating to activation of pro-tumorigenic components such as macrophages, neutrophils, dendritic cells and by impairing the immunosurveillance through the inhibition of TILs with cytotoxic activity. 16 UNIPROT:P05412 activates Neoplasms MESH:D009369 Protein 682cee82-5cbe-11e7-bcb7-001a4ae51246 PMC4692215 In contrast, in the three tumors (Fig. 1E,right panel) with low levels of GSTP1, phospho-JNK and phospho-cJun levels were significantly elevated relative to total JNK and total cJun, respectively. 16 MESH:D000431 activates Neoplasms MESH:D009369 Phenotype 96429378-c46a-11e5-91a7-001a4ae51247 PMC4099059 A recent study further indicated that alcohol and LPS treatments synergized with HCV NS5A to enhance the rate of hepatic tumors through a progenitor cell marker, Nanog[44](Fig. 3B). 16 UNIPROT:P59665 inhibits Neoplasms MESH:D009369 Protein 43a9c13c-3c82-11f0-8cae-0050569a1f61 10.1016/j.biochi.2022.04.011 HNP1 reduces tumor volume and tumor metastasis and prolongs survival by acting on tumor angiogenesis [116]. 16 MESH:D008545 activates Neoplasms MESH:D009369 Phenotype 13a37240-47f3-11e6-82ce-001a4ae51247 10.1074/jbc.273.26.16501 Tumorigenicity and Metastatic Potential of AP-2-transfected Melanoma Cells We have previously demonstrated that enforcedMCAM/MUC18expression in the primary cutaneous melanoma SB-2 cells increases tumor growth and metastatic potential in nude mice (9). 16 PF:PF09179 activates Neoplasms MESH:D009369 ProteinFamily 783f0d1e-04ef-11f0-bb39-0050569a791b 10.1016/j.pccm.2024.08.002 Upregulation of MHC-I could potentiate the tumor killing of EGFR-TKI.30Moreover, a certain subgroup of TILs may contribute to EGFR-TKI resistance. 16 UNIPROT:P50591 activates Neoplasms MESH:D009369 Protein ce81be82-cb2a-11e5-b419-001a4ae51246 11940602 Note that tumor lines such as prostate cancer PPC-1, ovarian cancer OCVAR-3, and cervical cancer HeLa are triggered by the combination of PPARγ modulators and TRAIL to undergo apoptosis (Fig.2,AandB), activate caspases (Fig.2C), and cleave the caspase substrate PARP (Fig.2D). 16 UNIPROT:P61278 inhibits Neoplasms MESH:D009369 Protein de1f4be6-3510-11e8-9192-001a4a160175 26643525 Somatostatin analogues (SSa) are used to control hormone-related symptoms and to decrease tumor burden both in functionally and non-functionally P-NETs (Baudin et al., 2012). 16 PF:PF01877 activates Neoplasms MESH:D009369 ProteinFamily 658430b4-cb8d-11e5-a7a8-001a4ae51246 11112771 YLR136c bears homology to mammalian TIS, an RNA-binding protein that promotes deadenylation and degradation of the tumor necrosis factor-α mRNA, thereby, regulating tumor necrosis factor-α mRNA half-life (41,42). 16 CHEBI:49482 activates Neoplasms MESH:D009369 Chemical b7874b3a-869f-11f0-86f5-0050569a1f61 PMC7864390 The specificity of the gold nanoparticle conjugates (AuNP5kPEGPSMA-1-Pc4; 26.5 ± 1.1 nm in diameter) was initially evaluatedin vitroin PC3pip (PSMA-positive) and PC3flu (PSMA-negative) prostate cancer cells, which demonstrated 8-fold greater photodestruction of the PC3pip (PSMA-positive) cells.In vivo,the AuNP5kPEG-PSMA-1-Pc4 nanoparticles exhibited 4-fold greater accumulation in PC3pip (PSMA-positive) tumors than in PC3flu (PSMA negative) tumors, demonstrating that molecular specificity of the gold nanoparticles can directly enhance the tumor selective bulk delivery in receptor-overexpressing tumors (Fig. 12B). 16 UNIPROT:P19875 activates Neoplasms MESH:D009369 Protein 41b7c87c-04c6-11f0-bb39-0050569a791b 10.1016/j.lfs.2024.122951 For instance, the upregulation of IL-1β expression in lung cancer cells stimulates the secretion of VEGF and C-X-C motif chemokine ligand 2 (CXCL2), promoting angiogenesis and tumor growth [84]. 16 FPLX:HSPA activates Neoplasms MESH:D009369 ProteinFamily 29254a0c-3532-11e8-a51f-001a4a160176 24933225 Down-regulation of HSP70 using siRNA or various native/artificial inhibitors can limit or even reverse tumor development, demonstrating the significance of HSP70 inhibition in treating diseases (Goloudina et al., 2012). 16 MESH:D012194 activates Neoplasms MESH:D009369 Phenotype a8263566-c476-11e5-9cc6-001a4ae51246 26116412 Three cases of RT-induced tumor following Gamma-Knife treatment of a pituitary lesion have been reported[95,96]. 16 PF:PF00702 activates Neoplasms MESH:D009369 ProteinFamily 6d97ee6a-3528-11e8-a51f-001a4a160176 25240838 It is possible that a specific phospholipase (acyl hydrolase) is activated in the early stages to cause tumor growth and this phospholipase may be responsive to blockade by the hepoxilin-related analogs, PBTs. 16 UNIPROT:O43602 activates Neoplasms MESH:D009369 Protein 7ece1faa-1b86-11f0-aa93-0050569a1f61 10.1016/j.intimp.2024.112011 Furthermore, because combined therapy with DC vaccination and a PD-1 inhibitor induces T-cell cytotoxicity, improves OS, reduces tumor volume, and increases tumor cell apoptosis in HCC mice, this combination may constitute a viable therapeutic approach for HCC. 16 UNIPROT:O43602 inhibits Neoplasms MESH:D009369 Protein 17e93b62-5cad-11e7-bcb7-001a4ae51246 PMC5528727 In patients with advanced melanoma, treatment with local hyperthermia and injection of autologous DC reduced tumor growth and increased infiltration of CD8+ T cells, but overall survival was not improved (Guo et al., 2007). 16 UNIPROT:P80098 activates Neoplasms MESH:D009369 Protein 87ba40a6-380c-11e6-b56c-001a4ae51246 PMC4392281 Next, because CCL7 is known to promote proliferation of breast cancer cells (34), we examined whether CCL7 augments the self-renewal of tumor initiating cells. 16 PF:PF00250 inhibits Neoplasms MESH:D009369 ProteinFamily 4905e0c2-37fd-11e6-9aa8-001a4ae51247 PMC4505455 The FOXO family of forkhead transcription factors promotes resistance to oxidative stress, suppresses tumor development, and enhances longevity/life span (13,53). 16 CHEBI:18406 inhibits Neoplasms MESH:D009369 Chemical f5835560-c466-11e5-91a7-001a4ae51247 PMC3938987 As a matter of the fact, it has been observed that a treatment of U87 glioma cells expressing the constitutively activated EGFR mutant, EGFRvIII with an activated AMPK adenovirus or AMPK-agonist AICAR inhibited the lipogenesis and glycolysis and the tumor growth derived from these cancer cellsin vitroandin vivo(Guo et al., 2009a). 16 MESH:D000068579 inhibits Neoplasms MESH:D009369 Phenotype a2d6be66-45a7-11f0-9ac3-0050569a1f61 10.1016/j.jconrel.2022.03.043 Celecoxib successfully restored tumor blood flow byi) decompression of tumor vasculature via reducing tumor-associated fibroblasts and disrupting fibronectin bundles andii) normalization of tumor vascular structure via inhibiting angiogenesis and increasing pericyte coverage. 16 UNIPROT:Q9UER7 activates Neoplasms MESH:D009369 Protein 551c7fc2-37fa-11e6-8a17-001a4ae51247 PMC4505457 Thus, DAXX enhances tumor growth by affecting several components of the autophagy machineryin vivo. 16 UNIPROT:P51606 activates Neoplasms MESH:D009369 Protein 21104752-352a-11e8-b868-001a4a160176 25536383 In contrast to these lung specific observations, in tumors of other organs like melanoma, AGE–RAGE interaction may further induce tumor growth and metastasis (Abe et al., 2004). 16 UNIPROT:P26842 activates Neoplasms MESH:D009369 Protein 683e1942-3c8e-11f0-86f5-0050569a1f61 PMC9555301 Similarly, CD27 agonist antibodies (mimicking CD70 signals from DCs) augmented peptide vaccine responses and vaccine-induced syngeneic tumor control (Riccione et al., 2018). 16 UNIPROT:P32970 activates Neoplasms MESH:D009369 Protein 683e1942-3c8e-11f0-86f5-0050569a1f61 PMC9555301 Similarly, CD27 agonist antibodies (mimicking CD70 signals from DCs) augmented peptide vaccine responses and vaccine-induced syngeneic tumor control (Riccione et al., 2018). 16 CHEBI:73339 activates Neoplasms MESH:D009369 Chemical 1bd0f954-1b18-11f0-85c3-0050569a1f61 10.1016/j.bbcan.2024.189121 Conversely, the use of the cholinergic receptor blocker methoctramine inhibits the formation of blood vessels within the tumor, impeding tumor growth [44,124]. 16 UNIPROT:P04732 activates Neoplasms MESH:D009369 Protein 0e176950-1a7e-11f0-a2ca-0050569a1f61 10.1016/j.ntm.2024.100045 Concurrently, the SIHMGA1-FVIO-mediated MTD therapy accelerated dendritic cell maturation, bolstered the expression of pivotal immune recognition molecules (alternatively known as human leukocyte antigens, HLA, class Ⅰ and class Ⅱ), augmented the infiltration of tumor-targeting T lymphocytes, and mitigated the immunosuppressive environment by reducing the expression of interleukin-1 and transforming growth factor β in myeloid suppressor cells. 16 UNIPROT:P24001 inhibits Neoplasms MESH:D009369 Protein 0f166e18-cb8d-11e5-a7a8-001a4ae51246 10636838 HGF/NK4 potently inhibits tumor growthin vivoby increasing tumor cell apoptosis without affecting the proliferation rate of tumor cells (15). 16 MESH:D000077276 inhibits Neoplasms MESH:D009369 Phenotype 077ad84c-bbd9-11e5-9b9d-001a4ae51247 10.1016/j.nutres.2006.01.002 The fact that the administration of lycopene with both low- and high-fat diets suppressed the incidence of tumors suggests that lycopene can effectively inhibit the progression of tumors. 16 UNIPROT:Q6P6C2 activates Neoplasms MESH:D009369 Protein 0ab37eec-0021-11f0-9c09-0050569a791b 10.1016/j.gene.2024.149125 In addition, the ALKBH5/SNAI2 axis increases tumor immune escape through the activating ligand of the immune checkpoint CD155 (Meng et al., 2024). 16 UNIPROT:Q96TA1 inhibits Neoplasms MESH:D009369 Protein ffc2b636-1ba2-11f0-85c3-0050569a1f61 10.1016/j.prp.2024.155223 In HCC xenograft tumor models, MEG3 inhibited HCC tumorigenesis and tumor progression[149]. 16 CHEBI:90295 inhibits Neoplasms MESH:D009369 Chemical 3bc85b44-c46f-11e5-8491-001a4ae51247 PMC4239619 EGCG/PLX4720 treatment significantly suppressed tumor growth in mice compared with mice treated with EGCG or PLX4720 alone (Fig. 4,KandL). 16 MESH:D008154 activates Neoplasms MESH:D009369 Phenotype bb8e6e36-3916-11e8-8f56-001a4a160175 24012706 Only one study applying chronic (1year) oral administration (drinking water) was retrieved (Lijinsky and Taylor, 1977), suggesting that lucanthone may induce the development of tumors in rat. 16 UNIPROT:P10145 inhibits Neoplasms MESH:D009369 Protein 3553d88c-f0ea-11ee-9aaa-0050569a1f61 10.1016/S1040-8428(03)00067-2 Treatment with paclitaxel and cetuximab downregulated the expression of VEGF, bFGF, IL-8, and MMP-9 and inhibited tumor-induced neovascularity compared with untreated controls. 16 UNIPROT:P10145 activates Neoplasms MESH:D009369 Protein 2c5e01aa-04dd-11f0-bb39-0050569a791b 10.1016/j.bcp.2024.116254 Consistently, Huang et al. have recently reported that, in TNBC preclinical models, CAA-derived CXCL8 supported tumor growth, EMT, metastatic dissemination as well as immune suppression. 16 UNIPROT:P10145 activates Neoplasms MESH:D009369 Protein ce266d40-1bf5-11f0-a2ca-0050569a1f61 10.1016/j.apsb.2023.12.010 As one of the major CXCR1/2 ligands, IL-8 (CXCL8) was overexpressed in solid tumors to promote tumor growth. 16 UNIPROT:P10145 inhibits Neoplasms MESH:D009369 Protein 2c5e01aa-04dd-11f0-bb39-0050569a791b 10.1016/j.bcp.2024.116254 Interestingly, they observed that the combined targeting of CXCL8 and PD-1 pathways increased the tumor immune response and synergistically inhibited tumor progression[147]. 16 CHEBI:29035 activates Neoplasms MESH:D009369 Chemical 7b521d8e-1bf1-11f0-b759-0050569a791b 10.1016/j.actbio.2023.12.047 The ionic Mn2+in Mn-based nano-contrast agents can be effectively combined with pH-responsive nano-carriers to achieve controlled release of Mn2+and enhance MRI of hypoxic tissues in tumors[165]. 16 UNIPROT:P14780 activates Neoplasms MESH:D009369 Protein 0a8126be-bbd3-11e5-9b9d-001a4ae51247 10.1016/j.canlet.2008.04.050 Indeed, the release of MMP-9/gelatinase-B as a consequence of neutrophil degranulation, promotes tumor invasion through the degradation of extracellular matrix components and allows the migration of tumor cells toward the blood circulation. 16 UNIPROT:P14780 inhibits Neoplasms MESH:D009369 Protein 3553d88c-f0ea-11ee-9aaa-0050569a1f61 10.1016/S1040-8428(03)00067-2 Treatment with paclitaxel and cetuximab downregulated the expression of VEGF, bFGF, IL-8, and MMP-9 and inhibited tumor-induced neovascularity compared with untreated controls. 16 UNIPROT:O00626 activates Neoplasms MESH:D009369 Protein 1858c23a-3749-11e8-a34b-001a4a160175 26432555 TAMs also express PD-L1 and produce chemokine CCL22, which further inhibits T cell proliferation and promotes Treg trafficking to the tumor. 16 UNIPROT:P09486 activates Neoplasms MESH:D009369 Protein c323c842-ca5c-11e5-9088-001a4ae51247 12590137 Taken together, the data suggest that osteonectin and osteoactivin may promote tumor invasion, at least in part, by increasing the production of specific MMPs. 16 FPLX:PDGF:BB activates Neoplasms MESH:D009369 ProteinFamily f48b93da-bbdc-11e5-8abe-001a4ae51246 10.1016/j.ccr.2005.01.017 PDGF-BB also promoted tumor angiogenesis and solid tumor growth in this model. 16 FPLX:LDH inhibits Neoplasms MESH:D009369 ProteinFamily e5c915dc-1ad9-11f0-b759-0050569a791b 10.1016/j.apsb.2024.09.012 Based on the controllable colloid stability technology developed by Gu et al.63, a further study conducted by Zhang et al.59showed that 108 nm LDH NanoAlum in a monodispersed (saturated with albumin) or aggregated (induced by the bridging effect of albumin) state exhibited completely different infiltration abilities to lymph nodes after subcutaneous injection.In vivodata showed that monodispersed LDH vaccines infiltrated into lymph nodes more quickly and induced a strong T cell immune response to inhibit the progression of solid tumors. 16 MESH:D019284 activates Neoplasms MESH:D009369 Phenotype 55c94e1a-2011-11e6-ae18-001a4ae51246 10.1074/jbc.272.38.23952 To determine the role of Ca2+mobilization in PKD activation by bombesin, quiescent Swiss 3T3 cells were treated with the tumor promoter thapsigargin. 16 MESH:D019284 activates Neoplasms MESH:D009369 Phenotype 14958300-cc24-11e5-b6ad-001a4ae51246 9545257 We repeated the adherent/nonadherent experiment using PMA, the chemokine RANTES (which produces a distinct calcium signal) (21,22), and the tumor promoter thapsigargin, which results in an intracellular calcium signal by blocking the intracellular calcium reuptake mechanism. 16 MESH:D003676 inhibits Neoplasms MESH:D009369 Phenotype 81456bdc-c463-11e5-9cbe-001a4ae51247 PMC4807285 Then, influence of dosing time on the ability of DFO to inhibit tumor growthin vitroandin vivowas studied. 16 UNIPROT:Q9NZQ7 inhibits Neoplasms MESH:D009369 Protein 537caebc-0550-11f0-bb39-0050569a791b 10.1016/j.bbamcr.2024.119752 Extracellular HMGB1 mediates AGER-mediated CD274/PDL1 expression, preventing the tumor from immunosurveillance [77] (Fig. 7). 16 UNIPROT:Q15070 inhibits Neoplasms MESH:D009369 Protein a2d6be66-45a7-11f0-9ac3-0050569a1f61 10.1016/j.jconrel.2022.03.043 The combination of erlotinib and HSA-PTX significantly reduced the size of 4T1 tumors by about 2-fold and 4-fold as compared to the HSA-PTX only group and the erlotinib only group, respectively. 16 MESH:D055752 activates Neoplasms MESH:D009369 Phenotype 4b573f1a-1bab-11f0-85c3-0050569a1f61 10.1016/j.ijbiomac.2024.130309 In MM and small cell lung cancer (SCLC), the USP7 inhibitor demonstrates significant tumor growth inhibition activity in P53 and mutant tumors, suggesting that blocking USP7 can inhibit tumor growth in vivo through mechanisms that are both dependent and independent of P53 [113]. 16 UNIPROT:Q99593 activates Neoplasms MESH:D009369 Protein 33d81fca-cb2a-11e5-8189-001a4ae51246 12151397 Previously, we observed that HOS levels were elevated in skin tumors induced in SENCAR mice by a two-stage experimental skin carcinogenesis protocol (25), which yields skin tumors harboring activating Ras mutations (35). 16 UNIPROT:P21810 inhibits Neoplasms MESH:D009369 Protein 7e917910-3800-11e6-8a17-001a4ae51247 PMC4433619 In light of current knowledge regarding influence of inflammation on tumorigenesis, it is predictable that biglycan, similar to decorin, might inhibit tumor growth of established tumors by creating the TLR2/4-mediated pro-inflammatory environment[83]. 16 CHEBI:52027 activates Neoplasms MESH:D009369 Chemical 93a3d26c-c474-11e5-91a7-001a4ae51247 26585505 DiD fluorescence signal in tumors taken out from all mice sacrificed at times ranging between 1 and 24h after administration of tL-D and tL-P was significantly greater than that for L-D and L-P liposome-treated mice, indicating that coating with a specific antibody directs the liposomes towards CD20-bearing tumor cells. 16 MESH:D020533 inhibits Neoplasms MESH:D009369 Phenotype 7ed061a2-1b86-11f0-b759-0050569a791b 10.1016/j.intimp.2024.112035 Recently Maione et al. conducted an experiment on transgenic mice model to show us that SEMA3A operates as an endogenous angiogenesis inhibitor that impedes tumor growth by normalizing the tumor vascular system[127]. 16 UNIPROT:Q19AV6 inhibits Neoplasms MESH:D009369 Protein 8a2bd108-e9f9-11ef-b449-0050569a791b 10.1016/j.bioorg.2024.108036 The SWS1 demonstrated its effectiveness in anIn-vivomodel using a B16-F10 mouse model, inhibiting tumor development by 66.1 %. 16 UNIPROT:Q14512 activates Neoplasms MESH:D009369 Protein 7fb078f4-cb28-11e5-9aa0-001a4ae51247 11148217 Ectopic expression of FGF-BP in adrenal adenocarcinoma cells causes a release of FGF2 and formation of highly vascularized tumors in nude mice (52). 16 MESH:D008687 inhibits Neoplasms MESH:D009369 Phenotype f5835560-c466-11e5-91a7-001a4ae51247 PMC3938987 Moreover, it has also been reported that metformin significantly inhibited the formation of tumor spheres derived from ovarian cancer cell lines and patient ovarian tumor cells and reduced ALDH+ovarian cancer stem cell subpopulationin vitro(Shank et al., 2012). 16 UNIPROT:P39687 inhibits Neoplasms MESH:D009369 Protein a8320efe-cbf1-11e5-b0dd-001a4ae51247 10400610 The linkage of this sequence to this tumor suppressive function through two convergent and independent lines of evidence provides an important insight that will ultimately lead to identification of other constituents of the clinically important pathway of pp32-mediated tumor suppression. 16 CHEBI:30751 activates Neoplasms MESH:D009369 Chemical 78440554-1c63-11f0-b759-0050569a791b 10.1016/j.gastha.2024.05.012 SCFAs also triggered autophagy in cancer cells to promote M2 polarization in Macs, accelerating tumor advancement. 16 UNIPROT:Q9BZF1 inhibits Neoplasms MESH:D009369 Protein 552e1eba-3815-11e6-b56c-001a4ae51246 PMC4423679 To further investigate whether ORP8 suppressed tumor growth in BALB/c nude mice via apoptosis, we analyzed the cleaved caspase-8 and caspase-3 in the xenograft tumor tissues. 16 MESH:D009569 activates Neoplasms MESH:D009369 Phenotype a52c71ca-053c-11f0-bb39-0050569a791b 10.1016/j.apsb.2024.05.010 Specifically, NPs smaller than 200 nm exploit the fenestration capability of the tumor vascular system and the absence of a fully functional lymphatic drainage system in tumor cells to amplify intra-tumor drug concentration and NP retention time (Fig. 5A and B) Ultrasound, radiation, high temperature, and nitric oxide (NO) treatments can further enhance tumor vascular permeability, augmenting NPs’ EPR effect. 16 MESH:D009569 activates Neoplasms MESH:D009369 Phenotype 564c5f82-cb28-11e5-a6cd-001a4ae51247 11313348 Moreover, addition of NO, H2O2, and FeCl3to EGTA-pretreated B16M cells again increased tumor cytotoxicity to values similar to those induced by NO and H2O2. 16 MESH:D009569 activates Neoplasms MESH:D009369 Phenotype a2d6be66-45a7-11f0-9ac3-0050569a1f61 10.1016/j.jconrel.2022.03.043 In 2018, the same group used a similar combination therapy, showing a 2- to 3-fold increase of NO production in C26 tumors than normal tissue and improved inhibition of tumor growth [155]. 16 MESH:D009569 inhibits Neoplasms MESH:D009369 Phenotype a2d6be66-45a7-11f0-9ac3-0050569a1f61 10.1016/j.jconrel.2022.03.043 The preferential generation of NO led to a 2-fold higher accumulation of the polymeric nanoparticle within C26 tumors and in turn inhibited tumor growth and metastasis. 16 UNIPROT:P35228 activates Neoplasms MESH:D009369 Protein e0ecb194-8dfc-11e7-a21f-001a4ae51246 PMC4912416 Although inhibition of Arg-1 with nor-NOHA and iNOS with L-NMMA mechanistically reduced the suppressive effect of murine and human tumor-derived MDSCs, these inhibitors are limited by their toxicity in humans[63]. 16 FPLX:PI3K activates Neoplasms MESH:D009369 ProteinFamily f5a7a9ca-04c5-11f0-9c9e-0050569a1f61 10.1016/j.cellsig.2024.111345 Both HIF-1α and the PI3K/Akt signaling pathway can induce EMT in the hypoxic microenvironment of tumors, thereby promoting tumor invasion. 16 FPLX:PI3K activates Neoplasms MESH:D009369 ProteinFamily 3866b884-3406-11e8-87fd-001a4a160176 28888995 PI3Kγ inhibition restores CD8+T cell activation and cytotoxicity, and synergizes with checkpoint inhibitors to promote tumor regression[85]. 16 FPLX:MMP activates Neoplasms MESH:D009369 ProteinFamily 92504012-3805-11e6-b56c-001a4ae51246 PMC4416873 Taken together, we conclude that silencing Smad2 or inhibiting the ERK signal pathway in mutant p53 cells can repress the synergy between mutant p53 and TGF-β in their tumor-promoting functions by affecting Smad3-dependent transcriptional regulation of MMPs and Slug. 16 FPLX:HIF1 activates Neoplasms MESH:D009369 ProteinFamily f5a7a9ca-04c5-11f0-9c9e-0050569a1f61 10.1016/j.cellsig.2024.111345 Both HIF-1α and the PI3K/Akt signaling pathway can induce EMT in the hypoxic microenvironment of tumors, thereby promoting tumor invasion. 16 FPLX:HIF1 activates Neoplasms MESH:D009369 ProteinFamily 4aa855c8-ab8d-11e6-90f5-001a4ae51247 26377897 For example, during tumor onset, HIF1α activation in TAMs might upregulate glycolytic metabolism and support cancer-related inflammation (via IL-1β production), whereas in established tumors, HIF1α expression in TAMs, MDSCs, DCs, and Treg cells would collectively promote angiogenesis and immunosuppression (via lactic acid, PD-L1 expression, adenosine-adenosine receptor interaction on DCs, etc.) to sustain tumor growth (Figures 2A–2C). 16 UNIPROT:P29965 activates Neoplasms MESH:D009369 Protein 17e93b62-5cad-11e7-bcb7-001a4ae51246 PMC5528727 Additionally, in murine melanoma, intratumoral injection of poly-IC markedly reduced tumor growth and prolonged survival, leading to complete eradication of tumors when combined with transfer of tumor-peptide-specific T cells, CD40L-expressing plasmids, or systemic Flt3L (Amos et al., 2011; Fujimura et al., 2006; Stone et al., 2009b){Salmon et al., in press}. 16 FPLX:VEGF activates Neoplasms MESH:D009369 ProteinFamily 14795d72-390c-11e8-a51f-001a4a160176 25175739 Tumor angiogenesis is induced by redox sensitive vascular endothelial growth factor (VEGF), that activate VEGF receptors on endothelial cells[43,120,196]. 16 FPLX:VEGF activates Neoplasms MESH:D009369 ProteinFamily a48ac92e-452e-11f0-8cae-0050569a1f61 10.1016/j.bbcan.2022.188750 Vascular endothelial growth factor (VEGF) is also upregulated in a variety of cancers, promoting tumor metastasis by generating highly permeable and disorganized blood vessels [47]. 16 FPLX:VEGF activates Neoplasms MESH:D009369 ProteinFamily 068415e6-4777-11e6-9af9-001a4ae51247 10.1074/jbc.272.27.17097 It is already established that hypoxia has both transcriptional and post-transcriptional effects on VEGF synthesis in several cell and tumor types (13,34), and our results indicate that the ET peptides are comparably potent for inducing VEGF transcription. 16 FPLX:VEGF activates Neoplasms MESH:D009369 ProteinFamily e079353c-3385-11e8-b868-001a4a160176 PMC7467856 This modeling aspect could be important if TGF-β and VEGF can synergize to enhance tumor vascularization. 16 FPLX:VEGF activates Neoplasms MESH:D009369 ProteinFamily 737b1b7c-4565-11f0-8cae-0050569a1f61 10.1016/j.lfs.2022.120500 Vascular endothelial growth factor (VEGF) increases angiogenesis of tumors by enhancing the growth and multiplication of endothelial cells and increasing the developing vascular precursor cells from the bone marrow and the permeability of vessels[45]. 16 FPLX:VEGF inhibits Neoplasms MESH:D009369 ProteinFamily 3553d88c-f0ea-11ee-9aaa-0050569a1f61 10.1016/S1040-8428(03)00067-2 Treatment with paclitaxel and cetuximab downregulated the expression of VEGF, bFGF, IL-8, and MMP-9 and inhibited tumor-induced neovascularity compared with untreated controls. 16 FPLX:VEGF activates Neoplasms MESH:D009369 ProteinFamily a5e2e63c-04c7-11f0-bb39-0050569a791b 10.1016/j.critrevonc.2024.104470 There have been many reports that TP53 mutations and activation of vascular endothelial growth factor (VEGF) promote tumor angiogenesis (Tokino and Nakamura, 2000). 16 FPLX:VEGF activates Neoplasms MESH:D009369 ProteinFamily 4f3a0870-bc14-11e5-8abe-001a4ae51246 PMC2442829 In addition, rapamycin acts cooperatively with small molecule inhibitors of c-met and VEGF, where in the latter study, combination therapy inhibited primary and metastatic growth of orthotopic pancreatic cancer tumors, as well as liver metastasis (Ma et al., 2005; Stephan et al., 2004). 16 FPLX:VEGF inhibits Neoplasms MESH:D009369 ProteinFamily 7b766968-390f-11e8-b868-001a4a160176 PMC6283356 VEGF blockade may increase T-cell trafficking to tumors, increase antitumor populations of T cells (CD8+ and CD4+ central memory), and decrease pro-tumor immune populations (myeloid-derived suppressor cells and regulatory T cells) [40]. 16 FPLX:VEGF inhibits Neoplasms MESH:D009369 ProteinFamily c16589b0-3403-11e8-bf76-001a4a160175 26071879 However, patient benefits are at best transitory since VEGF depletion ultimately induces vessel death, increases tumor hypoxia and causes tumor relapse[119]. 16 FPLX:Pertussis:toxin inhibits Neoplasms MESH:D009369 ProteinFamily cd39a6ba-04c9-11f0-baad-0050569a1f61 10.1016/j.ijbiomac.2024.134347 The drug version of PTX is taken up by the small intestine following oral administration and efficiently suppresses the growth of tumors. 16 CHEBI:25741 activates Neoplasms MESH:D009369 Chemical 9ba22468-340d-11e8-8636-001a4a160175 24731989 Ethylene oxide induced a variety of tumors in mice and rats in chronic bioassays[190]. 16 UNIPROT:Q08722 activates Neoplasms MESH:D009369 Protein 5c72e8e0-380b-11e6-aaca-001a4ae51246 PMC4423687 Exogenous treatment of TSP-1 may be able to suppress the CD47-mediated tumor immune escape by disrupting the CD47-SIRP-a interaction. 16 UNIPROT:P04040 activates Neoplasms MESH:D009369 Protein b436c93a-1c26-11f0-b759-0050569a791b 10.1016/j.ijbiomac.2023.129070 In addition, water-soluble catalase (CAT), an enzyme capable of decomposing H2O2, can serve as reactors, initiating the decomposition of endogenous H2O2in tumors and thereby enhancing tumor oxygenation to reverse the hypoxic TME [61–63]. 16 MESH:D020123 inhibits Neoplasms MESH:D009369 Phenotype faf8a9fe-5caf-11e7-8c5f-001a4ae51246 PMC4676726 Treatment of mice with rapamycin suppressed the proliferation of the well-vascularized region of the tumor, but dramatically enhanced the proliferation of the poorly vascularized region. 16 UNIPROT:P55273 inhibits Neoplasms MESH:D009369 Protein 17224a74-cb28-11e5-a6cd-001a4ae51247 11483609 To test this idea, the cDNAs were cloned into pcDNA3.1 Zeo and transfected into low-passage HEK293 cells in a standard colony survival assay, used previously to demonstrate the growth inhibitory properties of tumor suppressors such as p16 and p19 (15). 16 UNIPROT:P10451 inhibits Neoplasms MESH:D009369 Protein 9b856b66-cb28-11e5-a6cd-001a4ae51247 11564733 However, the weights of the OPN-induced tumors were reduced dramatically when anti-MMP-2 antibody was injected into the sites of the tumors (TableI). 16 UNIPROT:P08235 activates Neoplasms MESH:D009369 Protein 5106a484-3916-11e8-bf76-001a4a160175 24094150 For example, MnMEIO–Herceptin conjugates display an enhanced MR sensitivity which enables thein vivodetection of small tumors[106]. 16 UNIPROT:P45983 activates Neoplasms MESH:D009369 Protein 682cee82-5cbe-11e7-bcb7-001a4ae51246 PMC4692215 In contrast, in the three tumors (Fig. 1E,right panel) with low levels of GSTP1, phospho-JNK and phospho-cJun levels were significantly elevated relative to total JNK and total cJun, respectively. 16 UNIPROT:P05067 activates Neoplasms MESH:D009369 Protein 1c676042-cb2c-11e5-b419-001a4ae51246 12376527 100 ng/ml TPA treatment of cells has been reported previously to induce ectodomain shedding of APP, erbB4, and LRP by activating tumor necrosis factor-α converting enzyme (TACE) or other metalloproteases (19,22,25). 16 UNIPROT:P19971 inhibits Neoplasms MESH:D009369 Protein 29254a0c-3532-11e8-a51f-001a4a160176 24933225 In these studies TP inhibited the growth of mouse pancreatic cancer cells, suggesting that it could inhibit the development of pancreatic tumors in both humans and mice (Yokoyama et al., 2008). 16 UNIPROT:I7GQA7 activates Neoplasms MESH:D009369 Protein 6d97ee6a-3528-11e8-a51f-001a4a160176 25240838 It is possible that a specific phospholipase (acyl hydrolase) is activated in the early stages to cause tumor growth and this phospholipase may be responsive to blockade by the hepoxilin-related analogs, PBTs. 16 FPLX:PPAR activates Neoplasms MESH:D009369 ProteinFamily ce81be82-cb2a-11e5-b419-001a4ae51246 11940602 Note that tumor lines such as prostate cancer PPC-1, ovarian cancer OCVAR-3, and cervical cancer HeLa are triggered by the combination of PPARγ modulators and TRAIL to undergo apoptosis (Fig.2,AandB), activate caspases (Fig.2C), and cleave the caspase substrate PARP (Fig.2D). 16 IP:IPR023317 activates Neoplasms MESH:D009369 ProteinFamily 3197121c-cb8d-11e5-a7a8-001a4ae51246 10986284 These results thus suggest that inactivation of plasmin modulates angiogenesis in tumors. 16 UNIPROT:Q16552 activates Neoplasms MESH:D009369 Protein fcfff880-0538-11f0-bb39-0050569a791b 10.1016/j.apsb.2024.04.034 Furthermore, IL-17A promotes tumor angiogenesis by stimulating endothelial fatty acidβ-oxidation, enhancing the capacity to resist anoikis, and promoting tumor cell survival54. 16 MESH:D000069286 inhibits Neoplasms MESH:D009369 Phenotype 85e68ee2-5cb9-11e7-9833-001a4ae51246 PMC4705994 Bortezomib and ATRA alone did show some activity in this setting, but the bortezomib and ATRA combination regimen reduced tumor volume (Fig. 7B) compared with either agent alone. 16 FPLX:HES inhibits Neoplasms MESH:D009369 ProteinFamily 3ac33fbc-1b49-11f0-b759-0050569a791b 10.1016/j.ijbiomac.2024.132454 Importantly, CDDP-HA-Lip/Hes mitigates tumor inflammation, increases chemotherapy sensitivity, and inhibits tumor metastasis by suppressing the PI3K/Akt/mTOR pathway, with reduced adverse effects on normal tissues. 16 UNIPROT:Q8WXI8 inhibits Neoplasms MESH:D009369 Protein d68981e8-1b87-11f0-b759-0050569a791b 10.1016/j.cbi.2024.110940 In a Phase II clinical trial involving 13 relapsed and refractory MCL patients, P276-00 displayed notable effectiveness in overcoming treatment resistance and impeding tumor progression [96]. 16 PF:PF00800 activates Neoplasms MESH:D009369 ProteinFamily 4abf5206-04f2-11f0-bb39-0050569a791b 10.1016/j.humimm.2024.111090 Photodynamic therapy (PDT), a minimally invasive cancer treatment, involves enhancing the accumulation of a photosensitizer in tumor and after activation by a specific wavelength, molecular oxygen will be converted reactive oxygen species (ROS), which results in destruction of tumor cell. 16 UNIPROT:O95750 inhibits Neoplasms MESH:D009369 Protein 5e64e226-1b13-11f0-85c3-0050569a1f61 10.1016/j.pharmthera.2024.108669 Furthermore, in a mouse model lackingAbcb4andFxrgenes, which leads to spontaneous liver fibrosis and HCC due to bile acid metabolism dysregulation, administration of a non-proliferative FGF19 analogue (M52) suppressed both liver fibrosis and tumor growth. 16 UNIPROT:O60682 activates Neoplasms MESH:D009369 Protein aedab292-390e-11e8-a51f-001a4a160176 27491882 However, it is also shown that MSC-derived EVs stimulate tumor vascularization and tumor growth, which might induce undesirable off-target effects[180]. 16 CHEBI:45296 activates Neoplasms MESH:D009369 Chemical 48b691b8-4502-11f0-afc2-0050569a791b 10.1016/j.yacr.2022.04.014 Two of those are already included in the 2021 edition of the WHO Classification of CNS Tumors under the terms of CNS neuroblastoma, FOXR2-activated, and CNS tumor with BCOR internal tandem duplication, but others are emerging, too [41]. 16 CHEBI:79090 activates Neoplasms MESH:D009369 Chemical daa0ea14-cb8c-11e5-a7a8-001a4ae51246 10747974 In contrast, the p38 inhibitor SB202190, which inhibited tumor necrosis factor-α-mediated AP-1 activation had no effect on the ability ofH. 16 CHEBI:5759 inhibits Neoplasms MESH:D009369 Chemical f8cbf5a4-45af-11f0-afc2-0050569a791b PMC7688484 In an orthotopic mouse model of pancreatic cancer, we demonstrated that honokiol inhibited tumor growth and metastasis by targeting the crosstalk of tumor and stromal cells [151]. 16 PF:PF05932 activates Neoplasms MESH:D009369 ProteinFamily 891e0eac-e9e0-11ef-b5b7-0050569a1f61 10.1016/j.actbio.2025.01.005 This targeted CEST agent enabled tumor detection in mice even at low concentrations [87]. 16 MESH:D063646 activates Neoplasms MESH:D009369 Phenotype 8b5480ec-3543-11e8-bf76-001a4a160175 16368122 The level of TPA exposure was based on a prior carcinogenesis study where it was used to promote the skin and liver tumors initiated by transplacental cisplatin exposure (Diwan et al., 1993). 16 MESH:D063646 activates Neoplasms MESH:D009369 Phenotype 33d81fca-cb2a-11e5-8189-001a4ae51246 12151397 Previously, we observed that HOS levels were elevated in skin tumors induced in SENCAR mice by a two-stage experimental skin carcinogenesis protocol (25), which yields skin tumors harboring activating Ras mutations (35). 16 UNIPROT:P00533 activates Neoplasms MESH:D009369 Protein bb93d366-cbf0-11e5-83a8-001a4ae51246 9872991 Co-expression of EGFR and p185neu, each at low levels, in Er/neu cells greatly accelerated tumor appearance (∼2 weeks), and the tumors grew aggressively when compared with p185neucells that also expressed low level of oncogenic p185neu(>4–5 weeks). 16 UNIPROT:P00533 inhibits Neoplasms MESH:D009369 Protein f5835560-c466-11e5-91a7-001a4ae51247 PMC3938987 As a matter of the fact, it has been observed that a treatment of U87 glioma cells expressing the constitutively activated EGFR mutant, EGFRvIII with an activated AMPK adenovirus or AMPK-agonist AICAR inhibited the lipogenesis and glycolysis and the tumor growth derived from these cancer cellsin vitroandin vivo(Guo et al., 2009a). 16 CHEBI:9139 activates Neoplasms MESH:D009369 Chemical e0ecb194-8dfc-11e7-a21f-001a4ae51246 PMC4912416 In several syngeneic murine cancer models, sildenafil treatment slowed tumor growth, increased tumor infiltration with CD8+T-cells, upregulated T-cell activation markers CD69 and CD25, and decreased Tregproliferation[37,39,58]. 16 CHEBI:9139 inhibits Neoplasms MESH:D009369 Chemical e0ecb194-8dfc-11e7-a21f-001a4ae51246 PMC4912416 In several syngeneic murine cancer models, sildenafil treatment slowed tumor growth, increased tumor infiltration with CD8+T-cells, upregulated T-cell activation markers CD69 and CD25, and decreased Tregproliferation[37,39,58]. 16 UNIPROT:P05451 inhibits Neoplasms MESH:D009369 Protein 3b5ca9ec-003a-11f0-9c09-0050569a791b 10.1016/j.ijbiomac.2024.139063 Polygonatum sibiricumpolysaccharides (PSPs) could inhibit tumor growth and improve spleen index, thymus index, cytokine secretion, and CD4+/CD8+lymphocyte ratio. 16 MESH:D013752 activates Neoplasms MESH:D009369 Phenotype ed7d9422-e831-11e5-96c9-001a4ae51247 10.1074/jbc.272.47.29482 While the tumors in the tetracycline-treated animals (ribozme off) grew continuously and reached a size of 76 ± 20 mm2(Fig.4B,solid lines), the tumors in which the ribozyme was activated by removal of tetracycline started to regress and reached a size of 20 ± 3.5 mm2(Fig.4B,dotted lines). 16 MESH:D013752 inhibits Neoplasms MESH:D009369 Phenotype d958422e-e851-11e5-acc1-001a4ae51246 10.1074/jbc.272.40.25367 To confirm that tetracycline treatment repressed the expression of the transfected RIII in the RIII clone-formed tumors, we extracted total RNA from resected tumors. 16 CHEBI:44658 activates Neoplasms MESH:D009369 Chemical 995fd510-cb28-11e5-b419-001a4ae51246 11559703 In contrast to other protein phosphatases, the dephosphorylation activity of PP2C absolutely requires the metal cations, Mn2+or Mg2+, but its activity is not sensitive to the tumor promoter okadaic acid and other inhibitors of the PPP family (34). 16 MESH:D009538 activates Neoplasms MESH:D009369 Phenotype 30dcff8e-e9fc-11ef-95dd-0050569a1f61 10.1016/j.toxicon.2024.108209 In addition to the potential carcinogenic effects of nicotine itself, the nicotine metabolite cotinine and two of its derived metabolites, namely N′-nitrosonornicotine and nicotine-derived nitrosamine ketone, belong to the category of strong carcinogens and can induce tumor development (Murphy, 2021). 16 MESH:D009538 activates Neoplasms MESH:D009369 Phenotype dd34ee48-f193-11ee-b346-0050569a791b 10.1016/S0735-1097(02)02818-8 As we have shown previously, the effect of nicotine to enhance angiogenesis accelerates neovascularization and plaque growth in a hypercholesterolemic mouse model, and promoted tumor angiogenesis and tumor growth(5). 16 UNIPROT:P48061 activates Neoplasms MESH:D009369 Protein f92a171c-0043-11f0-9c09-0050569a791b 10.1016/j.pharmthera.2024.108765 Notably, stromal cell-derived factor-1α (SDF-1α) has been reported to similarly induce BM cell migration to tumor sites in the absence of VEGF, thereby promoting increased angiogenesis and the formation of irregular tumor vasculature (Reddy et al., 2008c). 16 UNIPROT:P61073 activates Neoplasms MESH:D009369 Protein 4e1dbaf0-45a7-11f0-8978-0050569a1f61 10.1016/j.jconrel.2022.03.024 The overexpression of CXCR4 and MMP2/9 enzymes at tumor sites further allows the nanoassemblies to target the tumor and subsequently experienced MMP2/9 enzymes cleavage. 16 UNIPROT:O15519 activates Neoplasms MESH:D009369 Protein 6833ea6e-3415-11e8-a51f-001a4a160176 16126242 These studies in combination with experimental studies, showing that c-FLIP expression promotes tumor escape from T cell surveillance in vivo, have lead to the assumption that c-FLIP is a potent tumor progressing factor (French and Tschopp, 1999). 16 UNIPROT:O15519 inhibits Neoplasms MESH:D009369 Protein 6833ea6e-3415-11e8-a51f-001a4a160176 16126242 Accordingly, recent studies have strongly suggested that cytotoxic drugs may promote tumors sensitization by decreasing c-FLIP expression (Hyer et al., 2002). 16 MESH:D015232 activates Neoplasms MESH:D009369 Phenotype 7a55bc06-f06e-11ee-b346-0050569a791b 10.1053/S1043-0679(03)00100-X Prostaglandin E2 (PGE2), a product of COX activity, is increased in human tumors and is suspected to promote tumor development. 16 MESH:D015232 inhibits Neoplasms MESH:D009369 Phenotype f8f0cfee-1a55-11f0-b40b-0050569a1f61 10.1016/j.jddst.2024.106376 In the 4T1 mouse breast cancer model and CT26 mouse colon cancer model, FASA/DOX treatment resulted in the suppression of cyclooxygenase (COX) expression, reduction in prostaglandin E2 (PGE2) levels, increased proportions of M1-type macrophages and IFN-γ+ CD8+T in tumor tissues, and attenuation of Treg cells, thereby improving the tumor immune microenvironment [10]. 16 MESH:D002216 activates Neoplasms MESH:D009369 Phenotype a2d6be66-45a7-11f0-9ac3-0050569a1f61 10.1016/j.jconrel.2022.03.043 Captopril markedly restored tumor blood perfusion and loosened endothelial junction, yielding a ~3-fold improvement in overall PTX-NP accumulation and a more uniform distribution within the tumor tissue (Fig. 6D). 16 UNIPROT:P25116 activates Neoplasms MESH:D009369 Protein 802a616e-abb0-11e6-9ac8-001a4ae51246 PMC4513102 Moreover, in cancers, endothelial ERK1/2 activation by PAR signaling has been implicated in resistance to angiogenic therapy (34), and activation of PAR-1 expressed on ECs by tumor-secreted matrix metalloproteinases promotes tumor progression (48). 16 FPLX:G:12:alpha activates Neoplasms MESH:D009369 ProteinFamily 3e6ec5fc-a1a7-11e6-9b40-001a4ae51246 10.1074/jbc.273.43.27816 Dominant negative ASK1(K709R) inhibited ASK1 activation induced by Gα12, Gα13, and tumor necrosis factor-α (Fig.3). 16 UNIPROT:Q15465 activates Neoplasms MESH:D009369 Protein 96e38740-3387-11e8-87fd-001a4a160176 27619253 SHH enhances tumor growth via a paracrine pathway wherein the tumor-derived SHH ligand induces hedgehog targeting genes in the surrounding stroma. 16 UNIPROT:P13688 activates Neoplasms MESH:D009369 Protein 457f9166-cb2c-11e5-a6cd-001a4ae51247 12122002 These observations suggest that CEACAM1-mediated tumor suppressionin vivois due, at least in part, to the ability of CEACAM1 to inhibit neovascularization by inducing the release of an antiangiogenic factor or factors that cause endothelial cell apoptosis. 16 UNIPROT:Q15303 activates Neoplasms MESH:D009369 Protein 1c676042-cb2c-11e5-b419-001a4ae51246 12376527 100 ng/ml TPA treatment of cells has been reported previously to induce ectodomain shedding of APP, erbB4, and LRP by activating tumor necrosis factor-α converting enzyme (TACE) or other metalloproteases (19,22,25). 16 MESH:D014212 inhibits Neoplasms MESH:D009369 Phenotype 85e68ee2-5cb9-11e7-9833-001a4ae51246 PMC4705994 Bortezomib and ATRA alone did show some activity in this setting, but the bortezomib and ATRA combination regimen reduced tumor volume (Fig. 7B) compared with either agent alone. 16 UNIPROT:O60238 inhibits Neoplasms MESH:D009369 Protein 537caebc-0550-11f0-bb39-0050569a791b 10.1016/j.bbamcr.2024.119752 Oncogenic KRAS-induced NIX reduces glucose flux into mitochondria, increases redox capacity through mitophagy, and maintains the mitochondrial pool, enhancing cell proliferation and promoting the progression of pancreatic neoplasia (PanIn) to carcinoma (PDAC) [101]. 16 CHEBI:114785 inhibits Neoplasms MESH:D009369 Chemical a2d6be66-45a7-11f0-9ac3-0050569a1f61 10.1016/j.jconrel.2022.03.043 The combination of erlotinib and HSA-PTX significantly reduced the size of 4T1 tumors by about 2-fold and 4-fold as compared to the HSA-PTX only group and the erlotinib only group, respectively. 16 UNIPROT:Q9Y6E0 inhibits Neoplasms MESH:D009369 Protein a5e2e63c-04c7-11f0-bb39-0050569a791b 10.1016/j.critrevonc.2024.104470 Serine/threonine-protein kinase 24 (STK24), a member of the germinal center kinase III (GCKIII) subfamily, inhibits the stemness of CD44 and suppresses tumor metastasis (Chen et al., 2021a). 16 CHEBI:50114 activates Neoplasms MESH:D009369 Chemical 984adbea-5631-11f0-86f5-0050569a1f61 10.1182/blood.V6.11.976.976 They have noted as well that estrogen in association with cortisone increases the resorption of the tumor in the female. 16 CHEBI:6498 activates Neoplasms MESH:D009369 Chemical 45947770-c46f-11e5-91a7-001a4ae51247 PMC4370320 For instance, depletion of regulatory T cells induced by cyclophosphamide treatment of patients with large established tumors caused significant tumor progression and this effect was suggested to be mediated by an increase in lipoxin A4 levels[135]. 16 CHEBI:5186 inhibits Neoplasms MESH:D009369 Chemical 84265374-1b6c-11f0-aa93-0050569a1f61 10.1016/j.phytol.2024.03.009 Similarly, fucoxanthin therapy decreased tumor growth while promoting the anoikis pathway in the carcinogenic mouse model.Kim et al., (1998)proved that fucoxanthin suppressed the mouse colon tumorigenesis caused by 1,2-dimethylhydrazine (Kim et al., 1998). 16 MESH:D056572 inhibits Neoplasms MESH:D009369 Phenotype 4f3a0870-bc14-11e5-8abe-001a4ae51246 PMC2442829 Combined treatment with an HDAC inhibitor and LY294002 inhibited tumor growth concurrently with inhibition of Aktin vivo. 16 MESH:D013755 activates Neoplasms MESH:D009369 Phenotype 70674f0c-cb29-11e5-8189-001a4ae51246 11592962 However, whether EGFR is involved in TPA-induced tumor promotion or cell transformation is not clear. 16 UNIPROT:P06494 activates Neoplasms MESH:D009369 Protein bb93d366-cbf0-11e5-83a8-001a4ae51246 9872991 Co-expression of EGFR and p185neu, each at low levels, in Er/neu cells greatly accelerated tumor appearance (∼2 weeks), and the tumors grew aggressively when compared with p185neucells that also expressed low level of oncogenic p185neu(>4–5 weeks). 16 FPLX:Chemokine activates Neoplasms MESH:D009369 ProteinFamily 1858c23a-3749-11e8-a34b-001a4a160175 26432555 TAMs also express PD-L1 and produce chemokine CCL22, which further inhibits T cell proliferation and promotes Treg trafficking to the tumor. 16 FPLX:Chemokine activates Neoplasms MESH:D009369 ProteinFamily 5694bbbe-cb29-11e5-b419-001a4ae51246 11606575 The v3 (or exon 7) insertion in the CD44v3 isoform has also been shown to contain heparin sulfate addition sites (62) required for the binding of heparin-binding growth factors, cytokines, and chemokines that promote tumor progression (11,63). 16 UNIPROT:P05231 inhibits Neoplasms MESH:D009369 Protein 60f270a2-ab9c-11e6-9646-001a4ae51246 PMC4571972 7E, the IL-6 and the VEGF-A antibody significantly decreased the tumor volume of HT29-shV xenografts. 16 UNIPROT:P25942 activates Neoplasms MESH:D009369 Protein 9e7f12ec-1bf3-11f0-b40b-0050569a1f61 10.1016/j.drup.2023.101041 CD40 agonist can promote the tumor-killing function of macrophages and restore immune cell surveillance of tumors. 16 UNIPROT:Q04206 activates Neoplasms MESH:D009369 Protein fabc5b40-1b0e-11f0-85c3-0050569a1f61 10.1016/j.drudis.2024.103989 (p65)Olaratumab can selectively bind to PDGFRα and block the receptor activation induced by PDGF-AA and PDGF-BB, thereby inhibiting the phosphorylation of PDGFRα and interfering with the conduction of downstream signals AKT and ERK, further delaying or preventing tumor growth, so as to achieve the purpose of treating tumors. 16 CHEBI:29108 activates Neoplasms MESH:D009369 Chemical f7c3a232-1acc-11f0-85c3-0050569a1f61 10.1016/j.nbd.2024.106710 It has been clearly established that dysregulation of calcium homeostasis mediated by acquired mutations of STING function led to excessive ER stress upon TCR stimulation, thereby inducing T cell death and promoting tumor immune escape, which necessitated STING palmitoylation and was also independent of IFN signaling (Wu et al., 2019;Wu et al., 2020). 16 CHEBI:29108 inhibits Neoplasms MESH:D009369 Chemical dc07d778-cbf0-11e5-b0dd-001a4ae51247 10488118 In contrast, whole blood ionized calcium levels were significantly reduced in mice bearing 293-legumain producing tumors and treated with PTHrP compared with mice bearing 293 control tumors and treated with PTHrP (Fig.6). 16 FPLX:Integrins activates Neoplasms MESH:D009369 ProteinFamily b87bbfba-1a54-11f0-b759-0050569a791b 10.1016/j.matbio.2024.11.002 Interestingly, α3β1 can exert paradoxical functions within the same type of cancer, switching from a tumor-promoting integrin at early stages during tumor development to a cancer-suppressive integrin at later stages during cancer progression. 16 CHEBI:8116 activates Neoplasms MESH:D009369 Chemical 7ca34f58-ca5e-11e5-9088-001a4ae51247 12621060 This is in good agreement with that of rat-DGKγ-C1A (3.6 nm), indicating that DGKγ is a new receptor of tumor-promoting phorbol esters. 16 FPLX:RAS activates Neoplasms MESH:D009369 ProteinFamily 7a624188-4572-11f0-afc2-0050569a791b PMC9239401 Some of these tumors include those produced by loss of an endocytic generab5,vps25,erupted, oravalanche, and epithelial malignant tumors produced by RasV12/scrib−/−or RasV12/dlg1−/−mutants. 16 FPLX:TGFB activates Neoplasms MESH:D009369 ProteinFamily e079353c-3385-11e8-b868-001a4a160176 PMC7467856 This modeling aspect could be important if TGF-β and VEGF can synergize to enhance tumor vascularization. 16 FPLX:TGFB activates Neoplasms MESH:D009369 ProteinFamily e394519c-340d-11e8-bf76-001a4a160175 24912116 The tumor-promoting effect of TGFβ is mostly seen in the later stages of epithelial cancers. 16 FPLX:TGFB activates Neoplasms MESH:D009369 ProteinFamily 88414f22-0037-11f0-9e78-0050569a1f61 10.1016/j.ijbiomac.2024.139113 TGF-β accelerates tumor growth and metastasis by stimulating tumor cell proliferation, suppressing immune cell activity, and promoting tumor angiogenesis [51]. 16 UNIPROT:P01133 inhibits Neoplasms MESH:D009369 Protein 637badde-354d-11e8-a51f-001a4a160176 15890525 This monoclonal antibody blocks the ligands EGF and TGF-alpha from binding to EGFR avoiding angiogenesis process, inhibiting tumor growth and eliciting both tumor regression and eradication of established tumors in murine xenograft tumor models[50]. 16 UNIPROT:P14210 inhibits Neoplasms MESH:D009369 Protein 0f166e18-cb8d-11e5-a7a8-001a4ae51246 10636838 HGF/NK4 potently inhibits tumor growthin vivoby increasing tumor cell apoptosis without affecting the proliferation rate of tumor cells (15). 16 UNIPROT:P14210 activates Neoplasms MESH:D009369 Protein b74d6ae4-c46e-11e5-9da3-001a4ae51247 PMC4143502 ATF-1 binding to the region between positions −1210 and −1123 of the promoter harboring a cAMP-responsive element (CRE) induced the repression of the promoter in response to hepatocyte growth factor (HGF) and played a key role in tumor progression triggered by HGF (Ghoneim et al., 2007). 16 UNIPROT:P84022 activates Neoplasms MESH:D009369 Protein 92504012-3805-11e6-b56c-001a4ae51246 PMC4416873 Taken together, we conclude that silencing Smad2 or inhibiting the ERK signal pathway in mutant p53 cells can repress the synergy between mutant p53 and TGF-β in their tumor-promoting functions by affecting Smad3-dependent transcriptional regulation of MMPs and Slug. 16 UNIPROT:Q15796 inhibits Neoplasms MESH:D009369 Protein f58fdb52-c46e-11e5-a92e-001a4ae51246 PMC4246091 Indeed, tumor growth and invasion in Min mice is accelerated by loss of Smad2 or Smad4 (7,8). 16 UNIPROT:Q00987 activates Neoplasms MESH:D009369 Protein 003333aa-8667-11f0-afc2-0050569a791b 10.1016/j.bcp.2021.114407 P52-ZER6 can enhance the binding of MDM2 and p53, promote p53 ubiquitination, and promote tumor progression[79]. 16 UNIPROT:Q00987 inhibits Neoplasms MESH:D009369 Protein 2e1bc026-ab9b-11e6-90f5-001a4ae51247 PMC4566238 We further validated that MDM2 knockdown or overexpression of p53 significantly blocked the growth of MCF-7-HBXIP cells in mice (Fig. 7,D–F, **,p< 0.01, Student'sttest), showing that HBXIP accelerated tumor growth by enhancing MDM2-mediated degradation of p53 in breast cancer cells. 16 MESH:D000255 inhibits Neoplasms MESH:D009369 Phenotype 75a6f19a-4557-11f0-86f5-0050569a1f61 10.1016/j.ijpharm.2022.121791 It has been demonstrated that the interaction of ATP with the P2X7 receptor can also cause tumor suppression. 16 IP:IPR000215 inhibits Neoplasms MESH:D009369 ProteinFamily 2f3e1e20-c8e0-11e5-9cb8-001a4ae51247 17028091 Maspin, a tumor-suppressing serpin (serine protease inhibitor;Table I, lines 13 and 14, highlighted inFig. 16 MESH:D007938 activates Neoplasms MESH:D009369 Phenotype 8165179c-ee17-11e5-872c-001a4ae51246 PMC4358135 RAW 264.7 (RAW) cells (American Type Culture Collection, Manassas, VA) are a mouse macrophage cell line that was originally established from a tumor induced by the Abelson murine leukemia virus. 16 FPLX:Wnt activates Neoplasms MESH:D009369 ProteinFamily 720314d4-ab9f-11e6-90f5-001a4ae51247 PMC4571965 Mechanisms for activation of Wnt signaling in human EOC tumors exhibit histotype dependence, with endometrioid EOC exhibiting mutations in β-catenin resulting in constitutively active Wnt signaling, although other histotypes do not harbor a significant level of activating mutations in this pathway (42). 16 UNIPROT:P04628 activates Neoplasms MESH:D009369 Protein 7026da42-5c75-11e7-bcb7-001a4ae51246 PMC6186419 In line, YAP/TAZ are detected in the nucleus of most cells composing Wnt1-induced mammary tumors (Park et al., 2015; Serrano et al., 2013) and are largely upregulated and nuclear in colon adenomas ofApcMin/+mice and in the hyperplastic epithelium forming after conditional knockout ofApcin the intestine (Azzolin et al., 2014; Cai et al., 2015; Camargo et al., 2007; Gregorieff et al., 2015). 16 UNIPROT:P35222 activates Neoplasms MESH:D009369 Protein 4f6eb69e-bc1c-11e5-9b9d-001a4ae51247 10.1016/j.proghi.2006.12.001 Immunohistochemistry reveals overexpression ofβ-catenin in between 50% and 80% of HCCs (Ihara et al., 1996;Suzuki et al., 2002) indicating that defects in other components contribute toβ-catenin activation in liver tumors. 16 GO:0006119 inhibits Neoplasms MESH:D009369 Phenotype b26175f4-0021-11f0-9f22-0050569a1f61 10.1016/j.prp.2024.155763 In HCC, PRC2 interacts with the pluripotency transcription factor NANOG to inhibit oxidative phosphorylation (OXPHOS) genes, thereby promoting the self-renewal and chemoresistance of tumor-initiating cells (TICs). 16 MESH:D001241 inhibits Neoplasms MESH:D009369 Phenotype 7da8e326-cc99-11e5-888a-001a4ae51246 PMC4003901 1, aspirin and SA inhibit tumor promotor (TPA)-induced transformation in a concentration-dependent manner. 16 UNIPROT:P16396 activates Neoplasms MESH:D009369 Protein a2d6be66-45a7-11f0-9ac3-0050569a1f61 10.1016/j.jconrel.2022.03.043 Orally administered enalapril augmented EPR-mediated bacteria accumulation in tumor tissues by 6–18-fold in both tumor models as compared to non-enalapril treated controls, likely because ACEi induced vessel dilation and enlarged endothelial gaps. 16 MESH:D005472 inhibits Neoplasms MESH:D009369 Phenotype cdd51776-04bf-11f0-bb39-0050569a791b 10.1016/j.ijbiomac.2024.134784 5-Fu can effectively inhibit tumor growth, and has better efficacy in digestive system cancer, and there will be some inflammatory reaction during the treatment. 16 MESH:D005472 inhibits Neoplasms MESH:D009369 Phenotype 24f620c4-ee16-11e5-872c-001a4ae51246 PMC4358260 In addition, Ki67 staining showed that 5-FU treatment decreased the percentage of proliferative cells in miR-520g tumors by 31% and in vector tumors by 77% (Fig. 3E). 16 UNIPROT:P25054 activates Neoplasms MESH:D009369 Protein 4a21b22c-cb8a-11e5-9498-001a4ae51246 10801778 These findings support the concept that an APC-related pathway may mediate bamacan up-regulation in colon tumors. 16 UNIPROT:P02778 activates Neoplasms MESH:D009369 Protein 0a8126be-bbd3-11e5-9b9d-001a4ae51247 10.1016/j.canlet.2008.04.050 Indeed, CXCL10/IP-10 was detected in metastatic sites of colorectal carcinoma cells, and promoted tumor invasion-related properties[100]. 16 UNIPROT:O43278 inhibits Neoplasms MESH:D009369 Protein 1419bc2a-bc39-11e5-9b9d-001a4ae51247 PMC4505473 When we use IPA to connect these genes based on previously known biological associations, a very robust signaling network is produced (p= 1 × 10−70, Fisher's exact test), with the tumor suppressors HAI-1/SPINT-1 and Stratifin (SFN) central to these connections (Fig. 4A). 16 UNIPROT:P07585 inhibits Neoplasms MESH:D009369 Protein 7e917910-3800-11e6-8a17-001a4ae51247 PMC4433619 In light of current knowledge regarding influence of inflammation on tumorigenesis, it is predictable that biglycan, similar to decorin, might inhibit tumor growth of established tumors by creating the TLR2/4-mediated pro-inflammatory environment[83]. 16 UNIPROT:P07585 inhibits Neoplasms MESH:D009369 Protein 0281e956-37fe-11e6-9aa8-001a4ae51247 PMC4397979 Supporting its tumor suppressor function, ectopic expression of DCN reduced the incidence of OSA and HOS-initiated tumor development as well as tumor size (Figure 7G). 16 UNIPROT:P08833 inhibits Neoplasms MESH:D009369 Protein de531ee6-bc43-11e5-8abe-001a4ae51246 10.1016/j.cytogfr.2005.01.010 Indeed, administration of IGFBP-1 could block the growth of MDA-MB-231 tumors in vivo[115,116]. 16 FPLX:HIF:alpha activates Neoplasms MESH:D009369 ProteinFamily 6f47e6da-5cc9-11e7-bcb7-001a4ae51246 PMC5012644 Similarly, both HIF-α subunits promote tumor growth in many non-ccRCC xenograft or autochthonous tumor models[77]. 16 UNIPROT:O14786 activates Neoplasms MESH:D009369 Protein 686e717a-3749-11e8-87fd-001a4a160176 26415628 Tumor-specific gemcitabine penetration was increased by binding neuropilin-1 (NRP1) receptor. 16 UNIPROT:P25653 inhibits Neoplasms MESH:D009369 Protein 76e6e96a-d9d4-11ee-b346-0050569a791b 10.1182/blood.V92.9.3018 Six of the patients were heterozygous for one or both of the known biallelic polymorphims at positions −67019and 836,20allowing evaluation of allelic loss in their tumors by DGGE analysis (Fig2). 16 FPLX:FOXO inhibits Neoplasms MESH:D009369 ProteinFamily 4905e0c2-37fd-11e6-9aa8-001a4ae51247 PMC4505455 The FOXO family of forkhead transcription factors promotes resistance to oxidative stress, suppresses tumor development, and enhances longevity/life span (13,53). 16 UNIPROT:Q5ATH1 inhibits Neoplasms MESH:D009369 Protein 96053b60-45b4-11f0-afc2-0050569a791b 10.1016/j.biosx.2022.100126 ApDC can inhibit tumor growth more effectively. 16 UNIPROT:Q9NYA1 activates Neoplasms MESH:D009369 Protein fb398244-1b47-11f0-b759-0050569a791b 10.1016/j.biopha.2024.116805 Sphingosine-1-phosphate (S1P) is a bioactive lipid catalyzed by sphingosine kinase 1 (SPHK1), which promotes tumor growth and metastasis by modulating the activity of HIF-1α and HIF-2α[142]. 16 UNIPROT:O43255 activates Neoplasms MESH:D009369 Protein 931651a6-aba2-11e6-9236-001a4ae51247 PMC4543648 Siah2 KD reduced the percentage of Ki67-positive cells, concomitant with an increased percentage of cells positive for active caspase-3 (Fig. 2,FandG), suggesting that Siah2 KD inhibits proliferation and promotes apoptosis in orthotopic prostate tumors. 16 UNIPROT:O43255 inhibits Neoplasms MESH:D009369 Protein 931651a6-aba2-11e6-9236-001a4ae51247 PMC4543648 Injection of control (pLKO.1) Rv1 cells resulted in formation of large prostate tumors, whereas injection of Siah2 KD (shSiah2) Rv1 cells under comparable conditions promoted an ∼10-fold reduction in the relative weight of tumors formed (Fig. 2E). 16 UNIPROT:P23760 activates Neoplasms MESH:D009369 Protein e7100a86-cb29-11e5-b419-001a4ae51246 11830592 Antisense Pax3 oligonucleotides induced apoptosis in melanoma tumors or in melanoma lines such as A375 (75), a phenomenon we have also observed in B16/F10.9 cells (not shown). 16 UNIPROT:Q92520 activates Neoplasms MESH:D009369 Protein 9944a3f0-bc44-11e5-9b9d-001a4ae51247 PMC2742305 When transfected into tumor cells, ILEI causes EMT, tumor growth, and metastasis. 16 UNIPROT:Q9NZI8 activates Neoplasms MESH:D009369 Protein 8e7b1e92-37fd-11e6-aaca-001a4ae51246 PMC4505587 The results also showed that relative CRD-BP mRNA expression was elevated in tumors and demonstrated that whereas some tumors expressed only one variant (either full-length CRD-BP or ΔN-CRD-BP), other tumors expressed both. 16 UNIPROT:O60216 activates Neoplasms MESH:D009369 Protein f333bf6e-d3fe-11e5-b157-001a4ae51247 PMC4807278 In our studies, the SCC1-initiated tumors produce pulmonary metastases in nude mice (34). 16 MESH:D002945 activates Neoplasms MESH:D009369 Phenotype 8b5480ec-3543-11e8-bf76-001a4a160175 16368122 The level of TPA exposure was based on a prior carcinogenesis study where it was used to promote the skin and liver tumors initiated by transplacental cisplatin exposure (Diwan et al., 1993). 16 MESH:D002945 activates Neoplasms MESH:D009369 Phenotype f5835560-c466-11e5-91a7-001a4ae51247 PMC3938987 Metformin was also effective at inhibiting the growth and promoting the anti-tumoral effect induced by cisplatin on tumor xenografts derived from SKOV3 tumor cell line and ALDH+ovarian cancer stem cellsin vivo(Shank et al., 2012). 16 CHEBI:135938 inhibits Neoplasms MESH:D009369 Chemical 96d6a932-340c-11e8-b868-001a4a160176 24667357 Lasofoxifene also reduced the mean number of tumors per rat as well as total tumor burden. 16 MESH:D008070 inhibits Neoplasms MESH:D009369 Phenotype 17e93b62-5cad-11e7-bcb7-001a4ae51246 PMC5528727 By contrast, another study on the same model reported that LPS only reduced tumor growth when given in the context of a GM–CSF–expressing whole-cell vaccine (Davis et al., 2011). 16 MESH:D008070 activates Neoplasms MESH:D009369 Phenotype 96429378-c46a-11e5-91a7-001a4ae51247 PMC4099059 A recent study further indicated that alcohol and LPS treatments synergized with HCV NS5A to enhance the rate of hepatic tumors through a progenitor cell marker, Nanog[44](Fig. 3B). 16 MESH:D008070 activates Neoplasms MESH:D009369 Phenotype a30a9efe-ca5d-11e5-9bd2-001a4ae51247 12540842 However, IL-6, IL-1β, and tumor necrosis factor-α levels induced by LPS mostly from macrophages were not different between STAP-2−/−mice and their wild-type littermates (data not shown). 16 MESH:D010455 activates Neoplasms MESH:D009369 Phenotype bb1d1a5c-1a5e-11f0-b40b-0050569a1f61 10.1016/j.jconrel.2024.10.037 By having three major properties of tumor vascular affinity, tumor penetration feature and protease recognition site, iNGR peptide allowed to bypass the barriers of tumor vascular and tumor stroma barriers [186]. 16 MESH:D010455 inhibits Neoplasms MESH:D009369 Phenotype 30f61668-cb2a-11e5-8189-001a4ae51246 12183450 Peptide K237 Suppressed Tumor Growth and Metastasis in Vivo To determine the effect of peptide K237 on tumor growth and metastasisin vivo, SCID mice were injected subcutaneously with human breast carcinoma cells (BICR-H1 cell line). 16 MESH:D010455 inhibits Neoplasms MESH:D009369 Phenotype 8b0a6e2c-001f-11f0-9f22-0050569a1f61 10.1016/j.jconrel.2024.11.076 Yanet al.form nanoclusters through gold thiol-mediated coordination and load peptide-based PROTAC to degrade tumor protein MDMX. 16 MESH:D010455 inhibits Neoplasms MESH:D009369 Phenotype 7b7cbdbc-3901-11e8-a51f-001a4a160176 26972276 Interestingly after 56days, treatment with peptide-targeted liposomes compared to untargeted ones significantly reduced the tumor size to the end of the study(p<0.0001). 16 MESH:D010455 activates Neoplasms MESH:D009369 Phenotype cc4cd884-cb27-11e5-8189-001a4ae51246 11335715 Co-administration of rhEndostatin with E37 peptide dramatically blocked the tumor growth inhibitory activity of the rhEndostatin (Fig.6). 16 FPLX:Cyclin activates Neoplasms MESH:D009369 ProteinFamily 84aaa856-1b1a-11f0-85c3-0050569a1f61 10.1016/j.bbcan.2024.189119 USP2 deubiquitinates several cell cycle regulators like Cyclin A1, Cyclin D1 and Aurora-A, enhancing their stability, cell cycle progression and tumor growth [202–204]. 16 GO:0030154 inhibits Neoplasms MESH:D009369 Phenotype 2c5e01aa-04dd-11f0-bb39-0050569a791b 10.1016/j.bcp.2024.116254 Current strategies to selectively target tumor-promoting CAFs include: i) blocking the differentiation from precursor cells via inhibition of precursor activation or key signaling pathways; ii) selective targeted depletion or specific antibodies; iii) induction of phenotypic switching toward tumor-restraining CAFs; iv) targeting the crosstalk between cancer cells and tumor-promoting CAFs. 16 UNIPROT:P06400 inhibits Neoplasms MESH:D009369 Protein 4fcdfe9c-18f1-11e6-8d81-001a4ae51247 10.1074/jbc.273.47.31528 SV40 Tag is a multifunctional protein; it has ATPase and helicase activities, it binds to DNA, and it associates with a number of proteins including the tumor suppressors pRB and p53, the pRB related proteins p107 and p130, and the transcriptional coactivator p300 (32-34). 16 UNIPROT:P06400 activates Neoplasms MESH:D009369 Protein bda264c6-cb2b-11e5-8189-001a4ae51246 11875067 We reported previously (50) that Rb and p27 could cooperate to enhance tumor development in a pituitary model independently of enhancement in the number of proliferating cells. 16 UNIPROT:P06400 inhibits Neoplasms MESH:D009369 Protein d68981e8-1b87-11f0-b759-0050569a791b 10.1016/j.cbi.2024.110940 Facaplysin inhibited Cdk4-related phosphorylation of pRb and induced G1 cell-cycle arrest in tumor (p16, pRb+) and normal (p16+, pRb+) cell lines. 16 UNIPROT:P42771 inhibits Neoplasms MESH:D009369 Protein 17224a74-cb28-11e5-a6cd-001a4ae51247 11483609 To test this idea, the cDNAs were cloned into pcDNA3.1 Zeo and transfected into low-passage HEK293 cells in a standard colony survival assay, used previously to demonstrate the growth inhibitory properties of tumor suppressors such as p16 and p19 (15). 16 UNIPROT:P46527 activates Neoplasms MESH:D009369 Protein bda264c6-cb2b-11e5-8189-001a4ae51246 11875067 We reported previously (50) that Rb and p27 could cooperate to enhance tumor development in a pituitary model independently of enhancement in the number of proliferating cells. 16 UNIPROT:P04141 inhibits Neoplasms MESH:D009369 Protein 48456cd0-cbf0-11e5-b0dd-001a4ae51247 10224095 Intravenous injection of CLDC containing the p53, angiostatin, or GM-CSF genes reduced tumor angiogenesis by levels comparable with the reduction in tumor angiogenesis produced by the implantation of a murine T241 fibrosarcoma cell line stably transfected with the murine angiostatin gene (24). 16 UNIPROT:P04141 activates Neoplasms MESH:D009369 Protein 7f2e7160-f0ea-11ee-8b99-0050569a1f61 10.1016/S1040-8428(03)00069-6 GM-CSF has also been demonstrated to be a potent stimulator of DC and to promote uptake of tumor antigens by DC. Systemic administration of GM-CSF has been studied in men with hormone-resistant prostate cancer (HRPC)[1]. 16 UNIPROT:P60568 activates Neoplasms MESH:D009369 Protein da39a6c0-bbfa-11e5-8abe-001a4ae51246 10.1016/S0169-409X(02)00043-1 Lymphokine-activated killer cells are either T or NK cells that have been mainly activated by interleukin 2 (IL-2) to enhance cell-mediated cytolysis of tumors. 16 UNIPROT:P60568 inhibits Neoplasms MESH:D009369 Protein 17e93b62-5cad-11e7-bcb7-001a4ae51246 PMC5528727 Intratumoral injection of an adenovirally encoded IL-2 also inhibits growth of distant, untreated tumors and protects mice from rechallenge with the same tumor type (Slos et al., 2001). 16 FPLX:TK inhibits Neoplasms MESH:D009369 ProteinFamily d2bb8fc6-cd20-11e5-aade-001a4ae51247 8557696 Similar alterations in TK cell cycle regulation with constitutive RNA expression and reduced fluctuations of protein expression and enzyme activity were described for other DNA tumor virus-transformed cells as well as tumor-derived cell lines but never in normal cycling cells (Hengstschlägeret al., 1994a, 1994b). 16 MESH:D051379 inhibits Neoplasms MESH:D009369 Phenotype 046edc34-1c69-11f0-b759-0050569a791b 10.1016/j.crbiot.2024.100228 Significantly reduced tumor weight and tumor volume values were evident in the DSY treatment group as compared to control mice, consistent with the pronounced suppression of PC tumor growth (Fig. 12A, B). 16 MESH:D051379 inhibits Neoplasms MESH:D009369 Phenotype d63795a8-1ba1-11f0-b759-0050569a791b 10.1016/j.jddst.2024.105504 The DOX-MSN-PEG was conjugated with folic acid (FA) or hyaluronic acid (HA) for site specific delivery.In vitroexperiments demonstrated a slow drug release pattern, at pH 5.5, for over 120 h. Moreover, exposure of 4T1 breast cancer mice to DOX-loaded MSNs could effectively inhibit tumor growth with reduced toxicity, while extending their survival up to 35 days. 16 MESH:D051379 activates Neoplasms MESH:D009369 Phenotype b0d40e4a-cb29-11e5-a6cd-001a4ae51247 11441025 The results of these experiments demonstrated that treatment of mice with this low dose of PAI-1 increased M21 tumor growth by 48% relative to the PBS control (data not shown), a result that exactly mirrors the increase in the growth of tumors treated with partially inactivated PAI-1 (Fig.1). 16 MESH:D051379 activates Neoplasms MESH:D009369 Phenotype c9da1ff2-352a-11e8-9192-001a4a160175 25795114 Kotin et al.[35,36]obtained tumors from diesel particulate extracts using strain A mice, indicating that higher doses might induce tumors in SENCAR mice. 16 MESH:D051379 activates Neoplasms MESH:D009369 Phenotype bda4ea3a-ca5d-11e5-9088-001a4ae51247 12519769 Prior to sacrifice, the mice were injected with EF5 to allow the visualization of hypoxic tumor regions (27,31). 16 MESH:D051379 inhibits Neoplasms MESH:D009369 Phenotype faf8a9fe-5caf-11e7-8c5f-001a4ae51246 PMC4676726 Treatment of mice with rapamycin suppressed the proliferation of the well-vascularized region of the tumor, but dramatically enhanced the proliferation of the poorly vascularized region. 16 UNIPROT:P01375 activates Neoplasms MESH:D009369 Protein a2d6be66-45a7-11f0-9ac3-0050569a1f61 10.1016/j.jconrel.2022.03.043 TNF-α at a low dose significantly enhanced the accumulation of 100-nm and 400-nm liposomes in subcutaneous B16BL6 melanoma tumors [166]. 16 UNIPROT:P01375 activates Neoplasms MESH:D009369 Protein 9944a3f0-bc44-11e5-9b9d-001a4ae51247 PMC2742305 Devoogdt et al. recently showed, using gene silencing, that secretory leukocyte protease inhibitor (SLPI), induced by TNF-α in lung carcinoma cells, was involved in the tumor-promoting activity of TNF-α by an as of yet unknown mechanism[69–71]. 16 MESH:D000860 activates Neoplasms MESH:D009369 Phenotype 38997bd6-1acf-11f0-a2ca-0050569a1f61 10.1016/j.semcancer.2024.10.001 Another member of the VEGF family involved in hypoxia-driven tumor lymph(angio)genesis and metastasis is PDGF-B[106–108]; importantly, HIF-1α was shown to promote lymphatic metastasis of breast CCs via direct transactivation of an intronic hypoxia-responsive element within thePdgfbgene, resulting in proliferative and chemotactic effects on hypoxic LECs[109]. 16 UNIPROT:P04637 activates Neoplasms MESH:D009369 Protein 7ba25cd8-0033-11f0-9c09-0050569a791b 10.1016/j.mam.2024.101335 However, mutation or inactivation of TP53 will lead to uncontrolled cell cycle regulation, allowing damaged cells to evade the checkpoint and enter an uncontrolled proliferation state, leading to increased genomic instability and promoting tumor progression (Benedict et al., 2018;Lossaint et al., 2022;Mandal et al., 2010). 16 UNIPROT:P04637 inhibits Neoplasms MESH:D009369 Protein 96e38740-3387-11e8-87fd-001a4a160176 27619253 IL-2, IL-12, and interferon gamma, classically associated with the Th1 response, have all been shown to induce apoptosis and growth inhibition of transduced pancreatic cancer cells in vivo.178-180TNF-α and interferon-β gene augmentation therapies have also been shown to potentiate the toxic effects of gemcitabine in vivo, leading to marked growth inhibition compared with either agent alone.181,182Despite promising results from an initial phase I/II trial of TNFerade, a TNF-α-carrying replication-deficient adenovirus, a recent randomized phase III trial found that LAPC patients treated with TNFerade combined with SOC chemoradiotherapy had no survival benefit compared with SOC only (median OS: 10.0 vs 10.0 months,p= 0.26).183 Tumor Suppressors p53 is inactivated in 70% of pancreatic adenocarcinomas, and multiple in vitro studies have shown that p53 gene therapy sensitizes pancreatic cancer cells to chemotherapy and RT.148,154,155Intraperitoneal delivery of a p53-carrying retrovirus in a mouse model of peritoneal carcinomatosis inhibited both the primary pancreatic tumor and peritoneal deposits.156OBP-702, a p53-armed oncolytic virus, suppressed the in vitro tumor cell viability more efficiently than p53-carrying adenovirus or unarmed oncolytic virus alone.157A phase III trial subanalysis showed that p53 gene therapy prolongs time to progression and survival in patients with favorable p53 expression profiles compared with those with unfavorable profiles (median OS: 7.2vs 2.7 months,p< 0.0001).158The SMAD4 tumor suppressor gene is deleted in over half of pancreatic cancers but in less than 10% of other cancers.148In vitro transfection of pancreatic cancer cells using SMAD4-carrying retrovirus resulted in apoptosis, and an in vivo study in mice showed that SMAD4-carrying adenovirus inhibited pancreatic tumor growth.159,160 Antiangiogenesis Genes Gene augmentation therapy with soluble decoy receptor (sVEGFR and sFGFR) genes to inhibit angiogenic growth factors has shown promising results. 16 UNIPROT:P04637 activates Neoplasms MESH:D009369 Protein 2e1bc026-ab9b-11e6-90f5-001a4ae51247 PMC4566238 We further validated that MDM2 knockdown or overexpression of p53 significantly blocked the growth of MCF-7-HBXIP cells in mice (Fig. 7,D–F, **,p< 0.01, Student'sttest), showing that HBXIP accelerated tumor growth by enhancing MDM2-mediated degradation of p53 in breast cancer cells. 16 UNIPROT:P04637 inhibits Neoplasms MESH:D009369 Protein 2fae4aa8-1b4a-11f0-b40b-0050569a1f61 10.1016/j.semcancer.2024.05.001 In MMTV-ras transgenic mice, p53 deficiency accelerated tumor proliferation and induced genomic instability and caused salivary tumors[114]. 16 UNIPROT:P04637 activates Neoplasms MESH:D009369 Protein f01522ec-1a84-11f0-b40b-0050569a1f61 10.1016/j.bbadis.2024.167455 We observed that p53-deficient xenografts were significantly suppressed, exhibiting the lowest tumor volume (Fig. 6B-E) and lightest tumor weight (Fig. 6F-G) compared to p53 wild-type xenografts when treated with the D + A combination (p< 0.05). 16 MESH:D008024 activates Neoplasms MESH:D009369 Phenotype 2aee6a26-3406-11e8-87fd-001a4a160176 28887205 Peptidic tumor receptor ligands such as68Ga-DOTATOC, an agonist for somatostatin receptors typically overexpressed by G1/G2 neuroendocrine tumors[67], or68Ga-PSMA, a ligand for prostate-specific membrane antigen (PSMA) in prostate cancer[68]are also widely used for PET tumor imaging in both patients and experimental animal studies. 16 FPLX:IL12 activates Neoplasms MESH:D009369 ProteinFamily 17e93b62-5cad-11e7-bcb7-001a4ae51246 PMC5528727 Intratumoral administration of IL-12 is associated with less toxicity and has shown to cause partial or complete tumor regression at the locally injected tumor site, but little to no response at distant sites (Rook et al., 1999; Sangro et al., 2004; Mahvi et al., 2007; Zapała et al., 2013). 16 GO:0006954 inhibits Neoplasms MESH:D009369 Phenotype af7a8b64-351c-11e8-bf76-001a4a160175 28527911 Strategies to hit CSCs by blocking such tumor-promoting inflammation are under investigation. 16 MESH:D003094 activates Neoplasms MESH:D009369 Phenotype 75d1e24a-cb29-11e5-b419-001a4ae51246 11682471 Notably, the amounts of collagen types I and V and proteoglycans were increased in CDT6-expressing tumors. 16 UNIPROT:P29083 inhibits Neoplasms MESH:D009369 Protein a1b12084-1a65-11f0-85c3-0050569a1f61 10.1016/j.prmcm.2024.100527 Fe(hino)3 effectively reduces tumor growth and inhibits metastasis in TNBC mouse models, with good tolerability and minimal systemic toxicity as stated in a Chinese study [112]. 16 UNIPROT:Q92565 inhibits Neoplasms MESH:D009369 Protein 6aa56cde-cb8d-11e5-a7a8-001a4ae51246 11116144 On the other hand, as suggested in a recent report, other GFRα receptors could interfere with the dimerization of mutant RET receptors, and therefore inhibit tumor development in tissues not involved in MEN2 syndromes (36). 16 FPLX:Fibrin inhibits Neoplasms MESH:D009369 ProteinFamily a2d6be66-45a7-11f0-9ac3-0050569a1f61 10.1016/j.jconrel.2022.03.043 This tumor-homing nanocage successfully reduced fibrin deposition in tumor tissues and led to an elevated tumor accumulation of Doxil®. 16 UNIPROT:P00750 activates Neoplasms MESH:D009369 Protein a2d6be66-45a7-11f0-9ac3-0050569a1f61 10.1016/j.jconrel.2022.03.043 To this end, Meiet al.incorporated tPA and antioxidants into nanoparticles (tPA@iRNP); tPA release effectively restored tumor blood flow and improved nanoparticle delivery by degrading fibrin clots and matrices whilst antioxidants inhibited tumor growth by scavenging ROS in C26 (colon cancer) tumor xenografts [140]. 16 UNIPROT:P60484 inhibits Neoplasms MESH:D009369 Protein 6b93177a-3406-11e8-bf76-001a4a160175 28898694 Many cancer cells suppress anoikis through the acquisition of activating mutations in anti-apoptotic, pro-survival pathways or loss of tumor suppressors such as PTEN (phosphatase and tensin homolog) (Paoli et al., 2013). 16 UNIPROT:P60484 inhibits Neoplasms MESH:D009369 Protein cec55b80-cb28-11e5-b419-001a4ae51246 11729185 Expression of PTEN in U87MG cells decreases tumor growth and increases the survival of mice implanted with these tumors (28). 16 UNIPROT:P60484 inhibits Neoplasms MESH:D009369 Protein 04648a32-45ad-11f0-afc2-0050569a791b 10.1016/j.bbcan.2022.188723 This mode of PTEN transfer might help PTEN suppress tumors, but it might also spread deleterious mutations of PTEN causing tumorigenesis[74]. 16 MESH:D008457 inhibits Neoplasms MESH:D009369 Phenotype e8753330-0547-11f0-bb39-0050569a791b 10.1016/j.prp.2024.155354 Three types of viruses, namely the adenovirus, the measles virus, and the herpes simplex virus have been shown to reduce tumor metastasis and growth in several tumors, such as lung cancer, glioma, breast cancer, hepatocellular carcinoma, pancreatic cancer, brain cancer and non-small cell lung cancer[133–135]. 16 MESH:D009765 activates Neoplasms MESH:D009369 Phenotype a94ba1e8-3aa7-11e8-8636-001a4a160175 27671038 They found that obesity promotes melanoma tumor growth, regardless of the presence or absence of leptin suggesting that leptin is not essential for tumor growth; energy restriction attenuates tumor growth in obese mice; leptin may accelerate tumor growth while leptin deficiency in the absence of obesity attenuates tumor growth; leptin receptors are expressed in mouse melanoma cells and there are a significantly increase in the proliferation of cultured B16-F10 cells. 16 UNIPROT:P16070 activates Neoplasms MESH:D009369 Protein d740b76c-3527-11e8-a34b-001a4a160175 25224289 These findings verified the role of CD44 receptor mediated endocytosis in CD44 overexpressing tumors. 16 UNIPROT:P16070 inhibits Neoplasms MESH:D009369 Protein 46911f6a-cb28-11e5-b419-001a4ae51246 11717318 For example, overexpression of soluble CD44 in mammary carcinoma or melanoma cells inhibits tumor growth and metastasis, but these effects are not obtained if the soluble CD44 is mutated such that hyaluronan binding does not occur (24-28). 16 UNIPROT:P36575 inhibits Neoplasms MESH:D009369 Protein 7ece1faa-1b86-11f0-aa93-0050569a1f61 10.1016/j.intimp.2024.112011 Furthermore, GPC3-positive HCC cells are eliminated by CAR (hYP7) T cells in mice with xenograft or orthotopic liver tumors. 16 UNIPROT:O81242 inhibits Neoplasms MESH:D009369 Protein 7ece1faa-1b86-11f0-aa93-0050569a1f61 10.1016/j.intimp.2024.112011 Furthermore, GPC3-positive HCC cells are eliminated by CAR (hYP7) T cells in mice with xenograft or orthotopic liver tumors. 16 UNIPROT:Q6UXD5 activates Neoplasms MESH:D009369 Protein 6c198d4c-bbda-11e5-8abe-001a4ae51246 10.1016/j.intimp.2007.01.008 "Instillation of PSK into a human gastric tumor mass prior to respective surgery causes T cells around the site to become tumor-infiltrating and develops significantly enhanced cytotoxic ""killer"" activity directed at the tumor." 16 UNIPROT:O43524 inhibits Neoplasms MESH:D009369 Protein 05c3be56-3c7b-11f0-86f5-0050569a1f61 10.1016/j.wneu.2022.04.009 As shown inFigure 5AandB, overexpression of FOXO3a reduced the volume and weight of tumor, and upregulated FOXO3a and SPRY2 knockdown increased the volume and weight of tumor. 16 CHEBI:16336 inhibits Neoplasms MESH:D009369 Chemical 46911f6a-cb28-11e5-b419-001a4ae51246 11717318 Administration of hyaluronan oligosaccharides also inhibits growth of several tumor typesin vivo, including mammary and lung carcinomas and melanoma (29).33S. Ghatak, S. Misra, J. Ward, and B. P. Toole, submitted for publication.Hyaluronan oligomers compete for endogenous polymeric hyaluronan-receptor interactions, resulting in monovalent rather than polyvalent interactions with receptors. 16 MESH:D010081 inhibits Neoplasms MESH:D009369 Phenotype d032fe7a-0019-11f0-9c09-0050569a791b 10.1016/j.intimp.2025.114013 The combined use of OXA liposomes and STING agonists reduces tumor growth potential by modulating the immune suppressive state of tumors, providing more effective and targeted methods for cancer treatment. 16 UNIPROT:Q15116 inhibits Neoplasms MESH:D009369 Protein 2c5e01aa-04dd-11f0-bb39-0050569a791b 10.1016/j.bcp.2024.116254 Interestingly, they observed that the combined targeting of CXCL8 and PD-1 pathways increased the tumor immune response and synergistically inhibited tumor progression[147]. 16 UNIPROT:O43623 activates Neoplasms MESH:D009369 Protein 0ab37eec-0021-11f0-9c09-0050569a791b 10.1016/j.gene.2024.149125 In addition, the ALKBH5/SNAI2 axis increases tumor immune escape through the activating ligand of the immune checkpoint CD155 (Meng et al., 2024). 16 UNIPROT:O43623 activates Neoplasms MESH:D009369 Protein 92504012-3805-11e6-b56c-001a4ae51246 PMC4416873 Taken together, we conclude that silencing Smad2 or inhibiting the ERK signal pathway in mutant p53 cells can repress the synergy between mutant p53 and TGF-β in their tumor-promoting functions by affecting Smad3-dependent transcriptional regulation of MMPs and Slug. 16 UNIPROT:Q9NQC7 activates Neoplasms MESH:D009369 Protein e2b6995e-3905-11e8-8636-001a4a160175 PMC5268070 Why so many different CYLD mutations produce tumors of skin origin is not known. 16 UNIPROT:Q9Y3T9 inhibits Neoplasms MESH:D009369 Protein 23e4c680-3758-11e8-a51f-001a4a160176 27721039 NIR exposed Dox*GO@Au and Dox*FA-GO@Au treated groups showed photothermal effects and caused further tumor size reduction to 68.4±2.13mm3and 57.1±1.62mm3respectively on 21st day of study. 16 UNIPROT:Q8NEB9 inhibits Neoplasms MESH:D009369 Protein 1079cc24-00ac-11f0-9e78-0050569a1f61 10.1016/j.prp.2024.155597 Conversely, high PIK3C3 levels inhibited metastatic tumor growth in cells with stable miR-338–5p expression. 16 UNIPROT:Q9BXY8 activates Neoplasms MESH:D009369 Protein fd903b0a-ab93-11e6-90f5-001a4ae51247 PMC4646217 Depletion of BEX2 significantly attenuated tumor initiation and progression ofTsc2−/−MEFs in nude mice (Fig. 3A). 16 CHEBI:79068 inhibits Neoplasms MESH:D009369 Chemical 6bf26c36-3913-11e8-8636-001a4a160175 24275090 ) administration of crocin increased rats life span and decreased tumor growth more intensely in female rats without showing any significant toxic effects (Garc-Olmo et al., 1999). 16 UNIPROT:O43504 activates Neoplasms MESH:D009369 Protein 2e1bc026-ab9b-11e6-90f5-001a4ae51247 PMC4566238 We further validated that MDM2 knockdown or overexpression of p53 significantly blocked the growth of MCF-7-HBXIP cells in mice (Fig. 7,D–F, **,p< 0.01, Student'sttest), showing that HBXIP accelerated tumor growth by enhancing MDM2-mediated degradation of p53 in breast cancer cells. 16 CHEBI:65329 inhibits Neoplasms MESH:D009369 Chemical 4f3a0870-bc14-11e5-8abe-001a4ae51246 PMC2442829 Combined treatment with an HDAC inhibitor and LY294002 inhibited tumor growth concurrently with inhibition of Aktin vivo. 16 CHEBI:517248 activates Neoplasms MESH:D009369 Chemical 8b336b38-001f-11f0-9f70-0050569a1f61 10.1016/j.jep.2024.118955 Bufalin, the principal active ingredient ofBufonidae(Chan chu), modulates tumor-infiltrating macrophages (TIMs) by shifting a tumor-driving M2 phenotype to a tumor-mitigating M1 phenotype. 16 CHEBI:6918 inhibits Neoplasms MESH:D009369 Chemical 2e00c782-e853-11e5-96c9-001a4ae51247 10.1074/jbc.272.42.26488 Similarly, the incomplete tumor promoter mezerein bound with lower potency to β2-chimaerin. 16 UNIPROT:Q99P91 activates Neoplasms MESH:D009369 Protein c323c842-ca5c-11e5-9088-001a4ae51247 12590137 Taken together, the data suggest that osteonectin and osteoactivin may promote tumor invasion, at least in part, by increasing the production of specific MMPs. 16 UNIPROT:Q05397 inhibits Neoplasms MESH:D009369 Protein d3f8fa26-3403-11e8-b868-001a4a160176 26099527 CDK4/6 dual inhibitors, such as palbociclib or abemaciclib, have shown anti-tumoral activity in experimental models, although data from breast does not confirm a particular benefit of CDK4/6 inhibition inCCND1amplified tumors.136 FAK, MYC (gains in chromosome 8q24) have broad gains described in 4% of HCC, with a single study reporting 26%.65,66FAK inhibition induces tumor responses in experimental models of HCC,137and selective inhibitors of FAK are currently under clinical development. 16 MESH:D005938 activates Neoplasms MESH:D009369 Phenotype 0be5437a-392e-11e8-9fbf-001a4a160176 9063588 Further studies indicated that the administration of an exogenous glucocorticoid also enhanced tumor growth. 16 MESH:D016572 activates Neoplasms MESH:D009369 Phenotype a5ecc4a4-f2bb-11e5-96ee-001a4ae51247 15253704 Both effects were mediated by cyclosporine A–induced production of tumor growth factor-β, which is also known to be a potent immunosuppressor. 16 MESH:D010778 activates Neoplasms MESH:D009369 Phenotype 7a669af2-1ae4-11f0-b759-0050569a791b 10.1016/j.ctrv.2024.102826 This PDT agent selectively induced significant tumor regression of both trastuzumab-sensitive and trastuzumab-resistant tumors with a single treatment session[149]. 16 MESH:D010778 activates Neoplasms MESH:D009369 Phenotype 4abf5206-04f2-11f0-bb39-0050569a791b 10.1016/j.humimm.2024.111090 Photodynamic therapy (PDT), a minimally invasive cancer treatment, involves enhancing the accumulation of a photosensitizer in tumor and after activation by a specific wavelength, molecular oxygen will be converted reactive oxygen species (ROS), which results in destruction of tumor cell. 16 MESH:D010778 inhibits Neoplasms MESH:D009369 Phenotype 6695ef4e-1a5f-11f0-aa93-0050569a1f61 10.1016/j.jddst.2024.106320 The merging of starvation therapy and improved PDT is anticipated to effectively inhibit tumor growth, ultimately leading to the complete elimination of the tumor (Fig. 8) [124]. 16 FPLX:p38 activates Neoplasms MESH:D009369 ProteinFamily a7b73ea0-ca01-11e5-9b70-001a4ae51247 PMC1224721 Most strikingly, 100% of colon cancer patients (total, 11) showed higher levels of p38γ signal in tumor tissues than in matched normal tissues (Fig. 8A,underlined). 16 UNIPROT:Q15672 activates Neoplasms MESH:D009369 Protein 7d457aba-c475-11e5-8491-001a4ae51247 25575080 To assess whether Twist1 also regulates the tumor-propagating potential in more advanced tumors, we transplanted FACS isolated TECs from SCC into immunodeficient mice following Twist1 deletion and found that Twist1 deletion decreased the proportion of TPCs by 100-fold (Figures 4C and 4D), indicating that Twist1 indeed modulates tumor stemness in both benign and malignant skin tumors. 16 MESH:D010712 activates Neoplasms MESH:D009369 Phenotype 2ee1e9a2-1c28-11f0-b40b-0050569a1f61 10.1016/j.addr.2023.115158 Intravenous injection of Ir-B-TiO2@CCM to mice enabled the determination of maximum accumulation of NPs at the tumor site by PA signal intensity changes, thereby realizing tumor treatment. 16 MESH:D002330 inhibits Neoplasms MESH:D009369 Phenotype c82af982-3954-11e8-8f56-001a4a160175 10487524 Penfluridol, which was highly potent in glioma cells, also enhanced bleomycin sensitivity by 90-fold in L1210 leukemia cells and by 4-fold in MCF-7 human breast cancer cells on clonogenic assays.In vivo, CPZ, when combined with the antineoplastic drug 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU), significantly inhibited the growth of experimental rat glioma tumors[46]. 16 UNIPROT:P42858 activates Neoplasms MESH:D009369 Protein 3fbce684-04d9-11f0-bb39-0050569a791b 10.1016/j.media.2024.103241 In this experiment, the inputs of all models are randomly sampled images with volume sizes of [128, 128, 128], and their performance is evaluated using the Dice Similarity Coefficient (Dice) and Hausdorff Distance (HD) on whole tumor (WT), enhancing tumor (ET), and tumor core (TC) (Hatamizadeh et al., 2022). 16 MESH:D003474 inhibits Neoplasms MESH:D009369 Phenotype 8b2d92d0-3c9c-11f0-b8fe-0050569a1f61 10.1016/j.onano.2022.100055 The above curcumin loaded MPEG-PCL micelles showed cytotoxicity to C-26 colon cancer cells and intravenous administration of curcumin loaded MPEG-PCL micelles (25 mg/kg curcumin) efficiently inhibited tumor growth through inhibiting angiogenesis in a mice model compared to free curcumin [80,81]. 16 MESH:D001835 activates Neoplasms MESH:D009369 Phenotype ffd3a04a-390a-11e8-8f56-001a4a160175 25437110 Briefly, colon neoplasia was induced by a weekly subcutaneous injection of 100μl of DMH (4mg/100g rat body weight), for 5 weeks, after which the rats were kept for an additional 10 weeks, under daily inspection. 16 MESH:D000236 activates Neoplasms MESH:D009369 Phenotype a8263566-c476-11e5-9cc6-001a4ae51246 26116412 The first human studies were prompted by excess post-RT mortality not accounted for by progression of the adenoma or RT-induced tumor. 16 UNIPROT:O14756 inhibits Neoplasms MESH:D009369 Protein 564c5f82-cb28-11e5-a6cd-001a4ae51247 11313348 HSE-induced tumor cytotoxicity in BSO-treated LD B16M cells was similar to that found in HD B16M cells, whereas HSE-induced tumor cytotoxicity in GSH ester-treated HD B16M cells decreased to values similar to those found in control LD B16M cells (TableIV). 16 UNIPROT:O14756 activates Neoplasms MESH:D009369 Protein db9cef7a-ca5c-11e5-8050-001a4ae51246 12578841 As shown in TableI, eNOS+/+HSE-induced tumor cytotoxicity is low (6) (approximately 15%). 16 UNIPROT:P49771 inhibits Neoplasms MESH:D009369 Protein 17e93b62-5cad-11e7-bcb7-001a4ae51246 PMC5528727 However, while vaccination with Flt3L prior to tumor challenge is able to prevent tumor development in both models, therapeutic application of Flt3L could not eliminate established tumors. 16 MESH:D014411 activates Neoplasms MESH:D009369 Phenotype 65c2b690-ac29-11e6-b1aa-001a4ae51246 PMC5009470 A SLN system containing cationic lipids was established to deliver miR-34a mimics into cancer stem cells (CSC), which cause tumor growth and drug resistance[135]. 16 UNIPROT:P08581 activates Neoplasms MESH:D009369 Protein 4f3a0870-bc14-11e5-8abe-001a4ae51246 PMC2442829 In addition, rapamycin acts cooperatively with small molecule inhibitors of c-met and VEGF, where in the latter study, combination therapy inhibited primary and metastatic growth of orthotopic pancreatic cancer tumors, as well as liver metastasis (Ma et al., 2005; Stephan et al., 2004). 16 UNIPROT:Q01105 activates Neoplasms MESH:D009369 Protein 3bc85b44-c46f-11e5-8491-001a4ae51247 PMC4239619 Silencing of SET significantly potentiated EGCG-induced suppression of tumor growth and increased survival rate (Fig. 3,GandH). 16 UNIPROT:P58004 activates Neoplasms MESH:D009369 Protein a4b20c30-c46b-11e5-91a7-001a4ae51247 PMC4276849 Sesn2 knockdown in these cells inhibited tumor growth (Fig. 6,A–E). 16 MESH:D001377 activates Neoplasms MESH:D009369 Phenotype a1b69848-cb28-11e5-b419-001a4ae51246 11562365 Kruse, S. D. Rose, and R. J. MacDonald, unpublished results.AR4–2J cells (ATCC CRL-1492) were derived from a rat acinar azaserine-induced tumor (37). 16 UNIPROT:P26358 activates Neoplasms MESH:D009369 Protein c98041d8-c46d-11e5-a92e-001a4ae51246 25452033 DNA methyltransferase (DNMT) inhibitors, such as azacitidine and decitabine, upregulate the expression of both minor histocompatibility antigens and putative tumor antigens, including members of the cancer testis antigen family. 16 UNIPROT:P26358 activates Neoplasms MESH:D009369 Protein d7f2ce4e-d470-11e5-8c94-001a4ae51246 25620649 DNA methyltransferase (DNMT) inhibitors, such as azacitidine and decitabine, upregulate the expression of both minor histocompatibility antigens and putative tumor antigens, including members of the cancer testis antigen family. 16 UNIPROT:P29375 activates Neoplasms MESH:D009369 Protein 9490b494-1a67-11f0-aa93-0050569a1f61 10.1016/j.critrevonc.2024.104532 Additionally, KDM5A inhibition with the selective KDM5A inhibitor CP1445 or the small molecule inhibitor, JIB 04, inhibited effectively tumor development in vitro and in TMZ-resistant GB in vivo (Banelli et al., 2017; Romani et al., 2019). 16 UNIPROT:O67480 activates Neoplasms MESH:D009369 Protein 546ec5e2-1b5a-11f0-85c3-0050569a1f61 10.1016/j.addr.2024.115306 This ICD enhances tumor-specific immune responses through mature DCs and increases tumor infiltration by T cells. 16 UNIPROT:Q6ZNE5 inhibits Neoplasms MESH:D009369 Protein 1079cc24-00ac-11f0-9e78-0050569a1f61 10.1016/j.prp.2024.155597 ATG14 act as suppresses tumors. 16 CHEBI:2981 inhibits Neoplasms MESH:D009369 Chemical e5221fdc-1a59-11f0-aa93-0050569a1f61 10.1016/j.bcp.2024.116598 Baicalin also blocked IL-17-induced intercellular adhesion molecule 1, vascular cell adhesion molecule 1, IL-6, and tumor necrosis factor-alpha mRNA expression in cultured synoviocytes, it’s also found that baicalin decreased the IL-17 induced production of IL-6 and TNF-α, thereby protecting joints from inflammation in mice. 16 MESH:D013217 activates Neoplasms MESH:D009369 Phenotype e9b31de2-1b37-11f0-b759-0050569a791b 10.1016/j.intimp.2024.112233 Although previous studies have shown that “starvation” therapy that blocks tumor blood supply can effectively inhibit tumor growth, if the blockade is not complete, it may create a more hypoxic microenvironment for solid tumors, which is not conducive to the penetration and infiltration of tumor chemotherapy drugs and adoptive cells[177]. 16 UNIPROT:P40763 activates Neoplasms MESH:D009369 Protein 152cc20c-1a48-11f0-b759-0050569a791b 10.1016/j.oor.2024.100688 In NPC, STAT3 activation by LMP1 leads to upregulation of PD-L1, supporting tumor immune escape. 16 UNIPROT:P40763 activates Neoplasms MESH:D009369 Protein 09dced36-1a6c-11f0-aa93-0050569a1f61 10.1016/j.nantod.2024.102521 Recent studies have identified the phenomenon of EML4-ALK fusion and phase separation of EML4-ALK to form condensates in lung cancer tumor tissue regions, which leads to hyperactivation of the MAPK/ERK cell signaling pathway and phosphorylation of the signal transducer and activator of transcription 3 (STAT3), enhancing the ability of the cancer cells to survive and maintain tumor proliferation (Fig. 3b). 16 UNIPROT:P40763 activates Neoplasms MESH:D009369 Protein b6f9f49e-351a-11e8-a51f-001a4a160176 28647610 These findings are consistent with studies indicating that STAT3 signaling in Tregs facilitates their capacity to augment melanoma and breast cancer tumor growth, and enhance Treg tumor infiltration[83,89]. 16 UNIPROT:P15941 activates Neoplasms MESH:D009369 Protein c87742c0-c46b-11e5-8491-001a4ae51247 PMC4271208 To determine how MUC1 induces tumor progression, we generated MUC1-overexpressing cells by introducing human MUC1cDNA into a human colon cancer cell line, HCT116 cells (HCT116/MUC1), and performed microarray analysis of mRNA using HCT116/MUC1 and HCT116/Mock cells to identify the differently expressed mRNA in these cells. 16 FPLX:Histone:H3 activates Neoplasms MESH:D009369 ProteinFamily 124be768-d9c4-11ee-b346-0050569a791b 10.1016/S0165-4608(98)00097-1 Four clones, H3(3-1), H3(3-2), H3(3-4), and H3(3-R2-1), produced tumors at all the injected sites, like the parental HSC-3 cells. 16 UNIPROT:Q15399 activates Neoplasms MESH:D009369 Protein bc6892f2-3c72-11f0-afc2-0050569a791b 10.1016/j.addr.2022.114365 The system promises real-time high-resolution imaging of the interaction between tumor fragments and TILs to assess TIL-mediated tumor killing and tumor responses to ICI treatments. 16 CHEBI:4027 activates Neoplasms MESH:D009369 Chemical 6e215f24-3406-11e8-a34b-001a4a160175 28899496 The extract can alleviate leukopenia and neutropenia induced by cyclophosphamide in both healthy mice and tumor bearing mice (Ghosh et al., 2006). 16 UNIPROT:P55042 activates Neoplasms MESH:D009369 Protein e6d5d202-f14b-11ee-b346-0050569a791b 10.1016/S0163-7258(03)00014-7 To enhance gene transfer by rAd vectors to tumors, vectors have been designed that bind to receptors that are preferentially up-regulated in these tissues. 16 FPLX:MYH activates Neoplasms MESH:D009369 ProteinFamily 7ece1faa-1b86-11f0-aa93-0050569a1f61 10.1016/j.intimp.2024.112011 The CAR structure resolves the issue of tumor immune escape caused by downregulation of the MHC and is independent of primary MHC antigen presentation, unlike the T-cell receptor (TCR) structure of normal T cells. 16 MESH:D013739 inhibits Neoplasms MESH:D009369 Phenotype de8f2152-bc43-11e5-8abe-001a4ae51246 10.1016/j.cytogfr.2005.01.005 Similar to female-specific cancers that are potentiated by estrogen and progestin, testosterone upregulates VEGF in prostrate epithelial cells and anti-angiogenesis treatments inhibit growth of prostate tumors[114]. 16 UNIPROT:P12272 activates Neoplasms MESH:D009369 Protein 99bbd416-352d-11e8-8f56-001a4a160175 PMC5773131 TGF- β stimulates the tumor cells to produce PTHrP, bone morphogenic proteins, insulin-like growth factors, fibroblast growth factors, platelet-derived growth factor that increase tumor growth. 16 MESH:D005492 activates Neoplasms MESH:D009369 Phenotype b56e5f72-04eb-11f0-bb39-0050569a791b 10.1016/j.ijpharm.2024.124494 A recent investigation described the formulation of a tumor microenvironment-responsive drug delivery system (SMFP-NPs) based on the preparation of silk fibroin nanoparticles (SF-NPs) boosted by manganese dioxide (MnO2), which were further manipulated by polyethylene glycol and folic acid to promote their stability and tumor attack (Wang et al., 2023). 16 MESH:D005492 activates Neoplasms MESH:D009369 Phenotype d63795a8-1ba1-11f0-b759-0050569a791b 10.1016/j.jddst.2024.105504 Additionally, folic acid conjugation increased the internalization of MSNs in tumors by binding with overexpressed folate receptors on the surface of tumor tissues [204]. 16 UNIPROT:Q9UNE0 inhibits Neoplasms MESH:D009369 Protein bf723ec8-351b-11e8-87fd-001a4a160176 28858736 The treatment of compound6jon DL solid tumor evidently impaired the tumor volume as measured by vernier caliper (Fig. 4A) and gradually repressed the tumor growth in dose dependent manner (Fig. 4B). 16 MESH:D008279 activates Neoplasms MESH:D009369 Phenotype b180d788-1b51-11f0-b759-0050569a791b 10.1016/j.clineuro.2024.108305 MRI revealed a large M1 enhancing tumor (Fig. 1). 16 MESH:D008279 activates Neoplasms MESH:D009369 Phenotype b5ccc4ec-3403-11e8-8636-001a4a160175 26087969 The superior contrast resolution of MRI compared with CT allows better delineation of both tumor volume and tumor extent within the prostate and periprostatic structures. 16 MESH:D008279 activates Neoplasms MESH:D009369 Phenotype 2f6f2c20-3749-11e8-a34b-001a4a160175 26409122 For instance, detection of early metastasis formation is visualized by BLI, while MRI enables accurate tumor volume determination at later stages[44]. 16 UNIPROT:O96013 activates Neoplasms MESH:D009369 Protein 6b6bc8a2-cb29-11e5-b419-001a4ae51246 11668177 To explore this possibility further, we sought to determine whether PAK4 could modulate the growth properties of a Ras-dependent tumor line. 16 UNIPROT:P10155 inhibits Neoplasms MESH:D009369 Protein de1f4be6-3510-11e8-9192-001a4a160175 26643525 Somatostatin analogues (SSa) are used to control hormone-related symptoms and to decrease tumor burden both in functionally and non-functionally P-NETs (Baudin et al., 2012). 16 PUBCHEM:151069 inhibits Neoplasms MESH:D009369 Chemical 46c4d6f0-cb2a-11e5-9aa0-001a4ae51247 12176997 At these doses, 17-AAG inhibits tumor growth in MCF-7 and BT-474 xenografts (data not shown). 16 UNIPROT:Q13822 activates Neoplasms MESH:D009369 Protein 9aeda718-1b32-11f0-b759-0050569a791b 10.1016/j.intimp.2024.112319 LPA and ATX work together as signaling molecules in the ATX/LAP axis to promote tumor progression and enhance tumor aggressiveness[13,17]. 16 UNIPROT:P08922 inhibits Neoplasms MESH:D009369 Protein 14795d72-390c-11e8-a51f-001a4a160176 25175739 Their antioxidant action scavenges ROS produced in the tumor microenvironment, reducing tumor neo-angiogenesis[194]. 16 CHEBI:33216 activates Neoplasms MESH:D009369 Chemical 29ebd540-c474-11e5-85e4-001a4ae51246 PMC5545120 If a specific BPA dose results in a high incidence of uterine lesions, that dose will be assessed further using global methylation and transcriptomic analysis to identify novel gene methylation targets driven by BPA and associated with uterine tumor and cancer development. 16 CHEBI:3088 activates Neoplasms MESH:D009369 Chemical fc0139b0-04c2-11f0-bb39-0050569a791b 10.1016/j.canlet.2024.217155 PTT and HIFU induce tumor necrosis and release heat-shock proteins by increasing local tumor temperature. 16 CHEBI:3088 inhibits Neoplasms MESH:D009369 Chemical 8360f76e-1b12-11f0-b40b-0050569a1f61 10.1016/j.jconrel.2024.06.001 Recent studies have shown that PTT inhibits tumor-associated macrophage polarization toward the M2phenotype, thereby inhibiting tumor growth [19]. 16 CHEBI:3088 activates Neoplasms MESH:D009369 Chemical 0a330288-1ad1-11f0-b759-0050569a791b 10.1016/j.bbcan.2024.189193 The BPQD-RMNV-based PTT, when combined with immune checkpoint-blocking antibodies, enhances CD8+T-cell infiltration and activity within TNBC tumors, effectively suppressing tumor growth in vivo [304]. 16 MESH:D012983 activates Neoplasms MESH:D009369 Phenotype f8e5d766-c46e-11e5-8491-001a4ae51247 PMC4256343 To further understand whether versican plays a tumor-promoting role in soft tissue neoplasms, we analyzed gene microarray expression data from 80 LMSs and 24 leiomyomas (Fig. 1G). 16 CHEBI:33709 activates Neoplasms MESH:D009369 Chemical 8f4a426a-390b-11e8-9fbf-001a4a160176 25497912 Consequently, amino acid radiotracers enable imaging of both low-grade tumors without BBB leakage and high-grade tumors with BBB leakage. 16 MESH:D006561 inhibits Neoplasms MESH:D009369 Phenotype e8753330-0547-11f0-bb39-0050569a791b 10.1016/j.prp.2024.155354 Three types of viruses, namely the adenovirus, the measles virus, and the herpes simplex virus have been shown to reduce tumor metastasis and growth in several tumors, such as lung cancer, glioma, breast cancer, hepatocellular carcinoma, pancreatic cancer, brain cancer and non-small cell lung cancer[133–135]. 16 UNIPROT:P10914 inhibits Neoplasms MESH:D009369 Protein e7100a86-cb29-11e5-b419-001a4ae51246 11830592 The down-regulation of Pax3 by IL6RIL6 may be implicated in the growth arrest of F10.9 cells in addition to the reported induction of tumor suppressors IRF-1 and p21/waf1 in these cells treated with IL6 and soluble IL6R (30). 16 CHEBI:37532 activates Neoplasms MESH:D009369 Chemical 60cd2c68-cb2b-11e5-9aa0-001a4ae51247 12480937 α-Cleavage is enhanced by phorbol ester-induced stimulation of tumor necrosis factor-α converting enzyme via protein kinase C and can be inhibited by metalloprotease inhibitors. 16 MESH:D003560 activates Neoplasms MESH:D009369 Phenotype 73a9665a-efd8-11ee-b346-0050569a791b 10.1016/j.ejrad.2003.09.003 BBB disruption may be a factor in tumor progression, and can be assumed in glioblastoma, where the simultaneous delineation of tumor necrotic cysts, sometimes associated with hemorrhages and solid, enhancing tumors parts, combined with reactive brain edema reflects histopathology[24]. 16 MESH:D018414 activates Neoplasms MESH:D009369 Phenotype 1858c23a-3749-11e8-a34b-001a4a160175 26432555 Decreased presence of ImCs in tumor-bearing mice noticeably improved CD4+ and CD8+ mediated tumor-specific immune response. 16 UNIPROT:P01106 activates Neoplasms MESH:D009369 Protein ea339f00-351e-11e8-9fbf-001a4a160176 PMC5329766 MYC induces distinct metabolic phenotypes in mouse liver and lung tumors, with liver tumors displaying enhanced glutamine catabolism and lung tumors retaining the ability to synthesize glutamine from glucose (Yuneva et al., 2012). 16 UNIPROT:P27487 activates Neoplasms MESH:D009369 Protein 5cfef8b4-00a5-11f0-9c09-0050569a791b 10.1016/j.gene.2024.148659 A study of chemotherapy resistance discovered that cisplatin treatment, with or without DPP-4 knockdown, suppressed carcinogenesis, implying that DPP-4 depletion may lower tumor burden in ECs. 16 UNIPROT:P04608 inhibits Neoplasms MESH:D009369 Protein 98ab8be0-352b-11e8-87fd-001a4a160176 27887988 For example, Tat-mediated delivery of a peptide derived from the C-terminus of p53 decreased tumor growth in intraperitoneal injection into mice with B-cell lymphoma[62]. 16 FPLX:AKT activates Neoplasms MESH:D009369 ProteinFamily bd124660-d7c0-11e5-b317-001a4ae51247 PMC4861415 Moreover, expression of RAP2A in cancer cells results in secretion of two matrix metalloproteinases (MMP2 and -9) and AKT phosphorylation at Ser-473, which promotes tumor invasion (80). 16 CHEBI:30741 activates Neoplasms MESH:D009369 Chemical 564c5f82-cb28-11e5-a6cd-001a4ae51247 11313348 Moreover, addition of NO, H2O2, and FeCl3to EGTA-pretreated B16M cells again increased tumor cytotoxicity to values similar to those induced by NO and H2O2. 16 MESH:D005334 activates Neoplasms MESH:D009369 Phenotype 099c539a-bbd3-11e5-9b9d-001a4ae51247 10.1016/j.canlet.2008.05.026 Second, hyperthermia itself caused the enhanced transcription of tumor antigens. 16 MESH:D005334 inhibits Neoplasms MESH:D009369 Phenotype 17e93b62-5cad-11e7-bcb7-001a4ae51246 PMC5528727 In patients with advanced melanoma, treatment with local hyperthermia and injection of autologous DC reduced tumor growth and increased infiltration of CD8+ T cells, but overall survival was not improved (Guo et al., 2007). 16 UNIPROT:P04626 inhibits Neoplasms MESH:D009369 Protein ed7d9422-e831-11e5-96c9-001a4ae51247 10.1074/jbc.272.47.29482 Down-regulation of HER-2/neu Expression Inhibits Tumor Growth in Vivo in Nude Mice When injected subcutaneously at 1 × 106cells/injection site into nude mice, SK-OV-3/tTA-7 control cells grew to a mean tumor size of 100 ± 20 mm2within 44 days (Fig.4A, •). 16 MESH:D047310 inhibits Neoplasms MESH:D009369 Phenotype 99811f44-cb29-11e5-8189-001a4ae51246 11451952 Apigenin reportedly inhibits hyaluronidasein vitro(46), in sperm penetration assays (47), and in mammary and cervix tumors (48). 16 UNIPROT:P15692 inhibits Neoplasms MESH:D009369 Protein 60f270a2-ab9c-11e6-9646-001a4ae51246 PMC4571972 7E, the IL-6 and the VEGF-A antibody significantly decreased the tumor volume of HT29-shV xenografts. 16 UNIPROT:Q9NR96 inhibits Neoplasms MESH:D009369 Protein 17e93b62-5cad-11e7-bcb7-001a4ae51246 PMC5528727 Of note, a different synthetic TLR9 agonist (with modified CpG motifs) reduced tumor growth and increased survival in a murine lung cancer model when combined with local tumor irradiation (Zhang et al., 2012). 16 CHEBI:60804 inhibits Neoplasms MESH:D009369 Chemical 0f5cd332-5ca8-11e7-b441-001a4ae51247 PMC4681002 The combination of P-CYP (HPMA copolymer–cyclopamine conjugate) and P-DTX (HPMA copolymer–docetaxel conjugate), as well as the P-CYP or P-DTX single treatment all inhibited the PC-3 prostate tumor growth to certain extent compared to saline group, immediately after three-week treatment (Fig. 2)[92]. 16 FPLX:EXT inhibits Neoplasms MESH:D009369 ProteinFamily 291e9fe0-0bf9-11e6-9449-001a4ae51247 10.1074/jbc.275.4.2269 Although it is clear that loss ofEXTgene function promotes cartilaginous tumor formation, the molecular mechanism of EXT-mediated tumor suppression in not known. 16 UNIPROT:O60259 inhibits Neoplasms MESH:D009369 Protein 2ee1e9a2-1c28-11f0-b40b-0050569a1f61 10.1016/j.addr.2023.115158 Under the specific action of cysteine (Cys), Aza-BDY NP disrupts the redox homeostasis of cells, releases sonosensitizers, initiates iron death, and finally inhibits tumors. 16 CHEBI:35549 activates Neoplasms MESH:D009369 Chemical d2ce9578-3946-11e8-bf76-001a4a160175 15135214 If the assumption is made that the PFOA-induced acinar cell tumors in rats in theBiegel et al. (2001)study are likely to have been the result of mechanisms that involve epigenetic or proliferative mechanisms as opposed to direct mutations, it is likely that the dose–response curve is nonlinear; therefore, it would be appropriate to consider benchmark-dose methodology in risk characterization. 16 HGNC:31542 activates Neoplasms MESH:D009369 Protein 65c2b690-ac29-11e6-b1aa-001a4ae51246 PMC5009470 Babar et al. examined whether the induction or withdrawal of miR-155 expression would cause tumor regression. 16 MESH:D018358 activates Neoplasms MESH:D009369 Phenotype 2aee6a26-3406-11e8-87fd-001a4a160176 28887205 Peptidic tumor receptor ligands such as68Ga-DOTATOC, an agonist for somatostatin receptors typically overexpressed by G1/G2 neuroendocrine tumors[67], or68Ga-PSMA, a ligand for prostate-specific membrane antigen (PSMA) in prostate cancer[68]are also widely used for PET tumor imaging in both patients and experimental animal studies. 16 UNIPROT:P53355 inhibits Neoplasms MESH:D009369 Protein 551c7fc2-37fa-11e6-8a17-001a4ae51247 PMC4505457 The opposite was true for two DAXX repression targets, the tumor suppressors DAPK1 and DAPK3 (Fig. 9C). 16 UNIPROT:Q12805 activates Neoplasms MESH:D009369 Protein e1eacac0-d478-11e5-9963-001a4ae51246 PMC4326844 All this indicates that Fibulin 3 promotes tumor growth in HCT116 cells through a mechanism dependent on p38α. 16 UNIPROT:Q12805 inhibits Neoplasms MESH:D009369 Protein e1eacac0-d478-11e5-9963-001a4ae51246 PMC4326844 Tumors sizes were significantly decreased by fibulin 3 knock-down in non-silenced cells, but not in p38α knock-down cells, where the size of the tumors was highly reduced, independently of fibulin 3 silencing (Fig. 9C). 16 CHEBI:351346 inhibits Neoplasms MESH:D009369 Chemical 5898368a-c46b-11e5-8491-001a4ae51247 PMC4260992 However, PEITC inhibits Akt, a component of Ras signaling to inhibit tumor growth in several cancer types[116–118]. 16 CHEBI:145535 activates Neoplasms MESH:D009369 Chemical 1e2fdd40-04bc-11f0-9c9e-0050569a1f61 10.1016/j.biopha.2024.117356 Under nanomolar or low micromolar, MLN4924 completely inhibits cullin neddylation to cause accumulation of many tumor suppressors in a variety of cancer cell lines[56], thus leading to growth arrest, apoptosis, senescence and autophagy, as well as sensitization of chemo-radiation in bothin vitrocell culture andin vivoxenograft tumor models, as well as inhibition of angiogenesis and inflammation[57–61]. 16 CHEBI:68647 inhibits Neoplasms MESH:D009369 Chemical 650f9336-45ad-11f0-86f5-0050569a1f61 10.1016/j.prp.2022.153886 A study conducted by Takuma et al.[121]revealed that regorafenib suppresses HCC cell proliferation and HCC tumor growth by decreasing cyclin D1viaalterations in intracellular and exosomal miRNAs in HCC, and it exerts antitumor effects by inducing cell cycle arrest in regorafenib-sensitive HCC cells, both invitroand invivo. 16 CHEBI:29866 activates Neoplasms MESH:D009369 Chemical 37840f10-c474-11e5-91a7-001a4ae51247 26239692 As in the earlier study,in uterosodium arsenite exposure alone induced ovarian tumors (benign epithelial adenomas, but not carcinomas) and did not induce liver tumors in females. 16 CHEBI:82303 activates Neoplasms MESH:D009369 Chemical cf3f0186-377f-11e8-9fbf-001a4a160176 10095124 CI Basic Red 9 induces a high incidence of liver tumors in mice, as well as liver, thyroid gland and Zymbal's gland tumors in rats[4]. 16 CHEBI:5614 inhibits Neoplasms MESH:D009369 Chemical 3f737444-3c98-11f0-afc2-0050569a791b 10.1016/j.ejphar.2022.175031 In three out of four mice, the potency of haloprogin monotherapy at a modest dose (1 μM) dramatically prevented tumor development and lowered the tumor volume by 574 ± 110 mm3than that of RAPTA-T monotherapy. 15 Neoplasms MESH:D009369 activates UNIPROT:Q9BZF1 Protein 552e1eba-3815-11e6-b56c-001a4ae51246 PMC4423679 The cleaved caspase-8 and caspase-3 in tumor tissues overexpressing ORP8 was higher than that in the mock group (Fig. 5C). 15 Neoplasms MESH:D009369 activates UNIPROT:P25445 Protein 403e56b6-2cab-11f0-aa93-0050569a1f61 10.1016/S1568-9972(01)00014-3 Thus, interferon-γ and tumor necrosis factor-α were able to upregulate surface Fas and Fas ligand, whereas interleukin 1-β downregulated surface Fas ligand. 14 Neoplasms MESH:D009369 activates UNIPROT:P05231 Protein 8d033516-e430-11e5-bc5d-001a4ae51247 10.1074/jbc.273.1.592 Characterization of Stable HPB-ALL Clones Transfected with the 32/36A Mutant IκBα The parental HPB-ALL cell line is a T cell tumor producing IL-2 and IL-6 in response to T cell activators, such as phorbol esters, in the presence of a Ca2+influx activators (PHA, ionomycin, CD3-specific antibodies, etc.). 14 Neoplasms MESH:D009369 activates UNIPROT:P60568 Protein 8d033516-e430-11e5-bc5d-001a4ae51247 10.1074/jbc.273.1.592 Characterization of Stable HPB-ALL Clones Transfected with the 32/36A Mutant IκBα The parental HPB-ALL cell line is a T cell tumor producing IL-2 and IL-6 in response to T cell activators, such as phorbol esters, in the presence of a Ca2+influx activators (PHA, ionomycin, CD3-specific antibodies, etc.). 14 Neoplasms MESH:D009369 phosphorylatesProtein UNIPROT:P35568 Protein 26aadde0-3934-11e8-b868-001a4a160176 16305809 Effects of tumor necrosis factor-alpha on serine phosphorylation TNF-alpha induces serine phosphorylation of IRS-1 through the inhibition of serine phosphatases or activation of serine kinases (Kanety et al., 1995). 14 Neoplasms MESH:D009369 activates GO:0001525 Phenotype 541cd32e-cb8a-11e5-984a-001a4ae51247 10944524 Antibody Antagonists of Integrin α5β1Block αvβ3-dependent Cellular Migration Recent studies show that antagonists of integrin α5β1or αvβ3can substantially block growth factor and tumor-induced angiogenesis in chicken embryos and in human skin transplanted onto SCID mice (15-18,32). 14 Neoplasms MESH:D009369 activates MESH:D013755 Phenotype 70674f0c-cb29-11e5-8189-001a4ae51246 11592962 EGFR Inhibitors Depress TPA-induced ERK Phosphorylation, AP-1 Activity, and Cell Transformation Although the tumor promotion activity of TPA is considered to be mediated mainly by PKC, activation of the EGFR tyrosine kinase has been found to increase in mouse epidermis with multiple topical treatments of TPA (11). 14 UNIPROT:Q03001 activates Neoplasms MESH:D009369 Protein df328bb4-376e-11e8-8636-001a4a160175 16483625 Tumor induction DMH, obtained from Sigma Chemical Company, St. Louis, MO, USA, was dissolved in 1 mM EDTA, adjusted to pH 6.5 with 1 mM NaOH and administered subcutaneously in the right thigh at a dose of 20 mg/kg b.w., once a week for the first 4 weeks. 14 UNIPROT:P35968 activates Neoplasms MESH:D009369 Protein bd4664ee-3810-11e6-aaca-001a4ae51246 PMC4375470 R-Ras Suppresses VEGFR2 Activation in Tumor Blood Vessels The level of VEGF is chronically elevated in tumors. 14 FPLX:VEGF activates Neoplasms MESH:D009369 ProteinFamily bd4664ee-3810-11e6-aaca-001a4ae51246 PMC4375470 R-Ras Suppresses VEGFR2 Activation in Tumor Blood Vessels The level of VEGF is chronically elevated in tumors. 14 UNIPROT:P00533 activates Neoplasms MESH:D009369 Protein c6182b3c-cb2a-11e5-8189-001a4ae51246 11950845 β-Catenin Is Tyrosine-phosphorylated in MMTV-Wnt-1 Tumors EGFR-induced tumor formation in the mammary gland is promoted by cooperative events with Wnt-mediated signaling, since both Wnt-1 and Wnt-3 were found to be up-regulated in tumor samples from WAP-TGFα transgenic animals (9). 14 FPLX:PKC activates Neoplasms MESH:D009369 ProteinFamily 70674f0c-cb29-11e5-8189-001a4ae51246 11592962 EGFR Inhibitors Depress TPA-induced ERK Phosphorylation, AP-1 Activity, and Cell Transformation Although the tumor promotion activity of TPA is considered to be mediated mainly by PKC, activation of the EGFR tyrosine kinase has been found to increase in mouse epidermis with multiple topical treatments of TPA (11). 14 CHEBI:16336 inhibits Neoplasms MESH:D009369 Chemical 5d81241e-cb2c-11e5-8189-001a4ae51246 12145277 Hyaluronan Oligomers Inhibit Tumor Growth in Vivo In a previous study we showed that administration of hyaluronan oligomers at the site of subcutaneous implantation of B16-F10 murine melanoma cells inhibits their growth by 50–85% depending on timing of exposure (15). 14 UNIPROT:P10301 inhibits Neoplasms MESH:D009369 Protein bd4664ee-3810-11e6-aaca-001a4ae51246 PMC4375470 R-Ras Suppresses VEGFR2 Activation in Tumor Blood Vessels The level of VEGF is chronically elevated in tumors. 14 CHEBI:37532 activates Neoplasms MESH:D009369 Chemical 77c903d6-83ba-11e6-9c3b-001a4ae51246 10.1074/jbc.272.49.31182 Sphingomyelinase Induces Tyrosine Phosphorylation of ErbB2 and ErbB3 in Fao Cells In the accompanying paper (21) we reported that treatment of the rat hepatoma cell line Fao with the tumor-promoting phorbol ester phorbol 12-myristate 13-acetate (PMA) resulted in the tyrosine phosphorylation of several proteins including focal adhesion kinase (FAK) paxillin, ErbB2, ErbB3, and unidentified proteins of 120–130 and ∼70 kDa. 14 UNIPROT:A6NDG6 activates Neoplasms MESH:D009369 Protein 379a0188-cb29-11e5-8189-001a4ae51246 11279018 Transient Expression of Pgp in Multicellular Tumor Spheroids We have previously reported on the development of an intrinsic Pgp-mediated MDR in multicellular prostate tumor spheroids of the DU-145 cell line, which paralleled the induction of cell quiescence in the depth of the multicellular tissue (7,8). 12 Neoplasms MESH:D009369 increases UNIPROT:Q9NZQ7 Protein eab02490-c46d-11e5-91a7-001a4ae51247 PMC4332778 In many tumors, PD-1 is up regulated in tumor infiltrating lymphocytes (TILs), while many tumors have increased PD-L1 expression[38]. 12 Neoplasms MESH:D009369 activates UNIPROT:P00533 Protein 9599c502-8640-11f0-9ac3-0050569a1f61 10.1016/j.celrep.2021.108875 It has recently been demonstrated that Yki-associated tumors produce the epidermal growth factor receptor (EGFR) ligand, Vein, to trigger autonomous EGFR signaling and produce the platelet-derived growth factor (PDGF)- and vascular endothelial growth factor (VEGF)-related factor 1 (Pvf1) ligand to non-autonomously activate PVR (PDGF and VEGF receptor-related) signaling and wasting in peripheral cells (Song et al., 2019). 12 Neoplasms MESH:D009369 activates UNIPROT:Q9Y4K0 Protein 9ddce0aa-5cdc-11e7-9fde-001a4ae51247 PMC4678039 Analysis of primary breast cancers revealed a heterogeneous pattern of expression with different tumors overexpressing LOX only; LOX and LOXL2; LOXL2 and LOXL4; or LOX, LOXL2, and LOXL4[53]. 12 Neoplasms MESH:D009369 activates UNIPROT:P28300 Protein 9ddce0aa-5cdc-11e7-9fde-001a4ae51247 PMC4678039 Analysis of primary breast cancers revealed a heterogeneous pattern of expression with different tumors overexpressing LOX only; LOX and LOXL2; LOXL2 and LOXL4; or LOX, LOXL2, and LOXL4[53]. 12 Neoplasms MESH:D009369 inhibits UNIPROT:P05164 Protein 22d27d72-1b13-11f0-b759-0050569a791b 10.1016/j.biopha.2024.116862 Baicalein could inhibit skin tumor progression in B[a]P-induced and 12-O-tetradecanoylphorbol-13-acetate (TPA)-promoted tumor model through suppressing TPA-induced production of the H2O2and myeloperoxidase (MPO), ornithine decarboxylase (ODC) activity and inflammatory responses[177]. 12 Neoplasms MESH:D009369 activates UNIPROT:P04626 Protein 2d80ee44-c46e-11e5-9cc6-001a4ae51246 PMC4079732 It has been reported that 25% of untreated primary prostate tumors, 78% of castrate metastatic tumors, and 59% of localized tumors after hormone treatment overexpress HER-2 protein[75]. 12 Neoplasms MESH:D009369 activates CHEBI:8764 Chemical c1c636d4-f1bb-11e5-96ee-001a4ae51247 17332737 With the introduction of more powerful immunosuppressive regimes the tumor incidence over time increased: azathioprine (AZA)