Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0178874 (tumor progression)
 40,807 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

With the exception of testis cancer, the variety of genitourinary cancers have not been found to be consistently responsive to chemotherapeutic agents or regimens for other than anecdotal short duration. This has generated keen interest in the possibility that biologic response modifiers might either directly or through manipulation of immune response mechanisms successfully prevent tumor progression in these systems. In recent years, those substances that have attracted the greatest attention have included interferon (and, more recently, recombinant gamma interferon), bacillus Calmette-Guerin (BCG), tumor necrosis factor, prostaglandin synthetase inhibitors, and interleukin-2. Results with each of these agents in the variety of genitourinary cancers have been both promising and disappointing. A number of mechanisms have been suggested to underlie the actions of each of these substances, and the successful or unsuccessful recruitment of these mechanisms, in the context of the particular intrinsic behavior of the cancers being treated, have been suggested as reasons for the treatment results that have been seen. Therapeutic efficacy has been described in the treatment of renal cell cancer by both systemic interferon and interleukin-2. Successful treatments have been reported in approximately 20% of patients treated with each substance, but generally, these results have been of short duration. Topical BCG has been used with great success to treat superficial transitional cell bladder cancer. In these instances, the generation of tumor necrosis factor has been suggested as possibly accounting for the 70% success rate both in therapy and prophylaxis that has been seen. Leukocyte-derived interferon and, more recently, recombinant gamma interferon, were found in initial trials to generate a 20% response rate in renal cell carcinoma patients. Enthusiasm for these agents, however, has been tempered more recently both by a failure to reproduce these results with any substantial duration as well as by the significant side effects that have been seen. Clearly, these agents continue to be intriguing both because of their intellectual appeal through the mechanisms by which they may be effective, as well as by the absence of any definitive therapy for the cancers they are being used to treat. An understanding of the complex host/tumor cell interaction that may ultimately determine therapeutic efficacy for each of these agents is undoubtedly critical if the role of these substances in the treatment of genitourinary cancer is to be successfully implemented, either alone or in combination with other treatment modalities.
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PMID:Biologic response modifiers in genitourinary neoplasia. 243 87

Fischer rats, in whom superficial transitional cell cancers of the urinary bladder were induced by the carcinogen N-[4-(5- nitrofuryl )-2-thiazolyl] formamide, were inoculated intraperitoneally with either phosphate buffered saline, indomethacin (a prostaglandin synthetase inhibitor), poly I:C (an interferon inducer), or indomethacin together with poly I:C. While indomethacin alone appeared to have a significant albeit variable inhibitory effect on tumor size, poly I:C had a far more pronounced significant inhibitory effect. The combination of poly I:C and indomethacin together, however, led to the greatest inhibition in tumor growth, and in some instances, to tumor regression. Splenic lymphocytes from the same animals demonstrated enhanced natural cytotoxicity after treatment with poly I:C. Surprisingly, levels of natural cytotoxicity seen in animals treated with indomethacin and poly I:C together were lower than those seen with poly I:C alone. No enhancement of cytotoxicity could be demonstrated in vitro in lymphocytes from indomethacin-treated animals. Macrophages were also treated in this system under identical conditions. However, the activity of macrophages alone and of macrophages and lymphocytes together did not appear to be modified either by indomethacin alone or by the combination of prostaglandin synthetase inhibition and interferon induction together, the combination of which in vivo was suggested to be most effective in controlling tumor progression. Further studies to determine timing of these interactions and doses of immune response modifiers in order to characterize mechanisms possibly at work in modifying tumor growth in this system therefore seem highly indicated.
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PMID:Indomethacin and poly I:C in the inhibition of carcinogen-induced bladder cancer in an experimental animal model. 620 90

MicroRNAs (miRNAs) are important gene regulators that play a profound role in tumorigenesis. Previous studies have revealed that miR-26b is downregulated in a wide range of malignant tumors and plays an important role in the regulation of carcinogenesis and tumor progression. In the present study, we revealed that miR-26b expression was decreased in human tongue squamous cell carcinoma and was associated with clinical stage, lymph node metastasis and survival prognosis. Ectopic expression of miR-26b suppressed the proliferation and metastasis of human tongue squamous cell carcinoma cells. Using a luciferase reporter assay, combined with western blot analysis results, we identified PTGS2 (prostaglandin-endoperoxide synthase-2, encoding COX-2) as the functional target of miR-26b. Specific inhibition of COX-2 activity by nimesulide further confirmed that miR-26b was able to regulate the cell proliferation and metastasis of the human tongue squamous cell carcinoma cells through a COX-2-dependent mechanism. Taken together, these results suggest that miR-26b serves as a tumor suppressor by targeting COX-2 and calls for the use of miR-26b as a potential therapeutic tool for human tongue squamous cell carcinoma, where COX-2 is often hyperactivated.
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PMID:miR-26b is downregulated in human tongue squamous cell carcinoma and regulates cell proliferation and metastasis through a COX-2-dependent mechanism. 2548 52

Skin cancer is the most common cancer, and exposure to ultraviolet (UV) radiation, namely UVA and UVB, is the major risk factor for skin cancer development. UVA is significantly less effective in causing direct DNA damage than UVB, but UVA has been shown to increase skin cancer risk. The mechanism by which UVA contributes to skin cancer remains unclear. Here, using RNA-Seq, we show that UVA induces autophagy and lysosomal gene expression, including the autophagy receptor and substrate p62. We found that UVA activates transcription factor EB (TFEB), a known regulator of autophagy and lysosomal gene expression, which, in turn, induces p62 transcription. Next, we identified a novel relationship between p62 and cyclooxygenase-2 (COX-2), a prostaglandin synthase critical for skin cancer development. COX-2 expression was up-regulated by UVA-induced p62, suggesting that p62 plays a role in UVA-induced skin cancer. Moreover, we found that p62 stabilizes COX-2 protein through the p62 ubiquitin-associated domain and that p62 regulates prostaglandin E2 production in vitro In a syngeneic squamous cell carcinoma mouse model, p62 knockdown inhibited tumor growth and metastasis. Furthermore, p62-deficient tumors exhibited reduced immune cell infiltration and increased cell differentiation. Because prostaglandin E2 is known to promote pro-tumorigenic immune cell infiltration, increase proliferation, and inhibit keratinocyte differentiation in vivo, this work suggests that UVA-induced p62 acts through COX-2 to promote skin tumor growth and progression. These findings expand our understanding of UVA-induced skin tumorigenesis and tumor progression and suggest that targeting p62 can help prevent or treat UVA-associated skin cancer.
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PMID:Adaptor protein p62 promotes skin tumor growth and metastasis and is induced by UVA radiation. 2872 34

Chemotherapy with a single chemotherapeutic agent or a combined chemotherapeutic regimen is the clinically standardized treatment for almost all human cancers. Upregulated expression of cyclooxygenase (COX)-2, also known as prostaglandin-endoperoxide synthase (PTGS), is associated with human carcinogenesis and cancer progression and COX-2 inhibitors show antitumor activity in different human cancers. Thus, a combination of chemotherapeutic agents with COX-2 inhibitors has been shown to improve therapeutic effects on human cancers. This review discusses and summarizes recent advances in cancer control and treatment using various antineoplastic drugs combined with COX-2 inhibitors. These combinations showed synergistic antitumor effects. At the gene level, COX-2 inhibitors can reduce inflammatory factors thereby regulating macrophage recruitment for activating the antitumor immune microenvironment; downregulating vascular endothelial growth factor (VEGF) to inhibit tumor angiogenesis; and inhibiting the PI3K/Akt signaling pathway to induce tumor cell apoptosis. In addition, such a combination can reduce toxicity and chemoresistance and enhance radiosensitivity, although COX-2 inhibitors-related cardiotoxicity may potentially affect its use. Further in-depth investigation of these drug combinations is needed to maximize antitumor efficacy and minimize the side effects.
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PMID:Combined chemotherapy with cyclooxygenase-2 (COX-2) inhibitors in treating human cancers: Recent advancement. 3254 Jun 42