Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0699790 (colon cancer)
 28,837 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Non-steroidal anti-inflammatory drugs have been shown to inhibit carcinogenesis in colon cancer, and to induce apoptosis in a variety of tumor cell lines. Some anti-tumor effects are thought to be related to their cyclooxygenase-2-inhibitory activity, but recent studies have shown that non-steroidal anti-inflammatory drugs exert their anti-tumor effect via cyclooxygenase-2-independent mechanism. SDX-308 (CEP-18082) is a non-cyclooxygenase-2-inhibiting indole-pyran analog and is structurally related to SDX-101, an R-enantiomer of etodolac. SDX-308 has a potent anti-myeloma effect and shows synergism in combination with other drugs for the treatment of chronic lymphocytic leukemia. In addition SDX-308 inhibits osteoclast formation and activity and thereby might be an attractive drug for the treatment of diseases with increased osteoclast activity such as osteolytic lesions in multiple myeloma and metastatic carcinomas, as well as osteoporosis. This review covers future application of SDX-308 as an anti-myeloma drug regulating increased osteoclast activity.
 ...
PMID:SDX-308 and SDX-101, non-steroidal anti-inflammatory drugs, as therapeutic candidates for treating hematologic malignancies including myeloma. 1784 46

Inhibitory effects and potential mechanisms of capecitabine metronomic chemotherapy on colon cancer were investigated in this study. Metronomic chemotherapy with fluorouracil or capecitabine inhibited proliferation of colon cancer cells both in vitro and in vivo. Capecitabine metronomic chemotherapy demonstrated equal effects as CTX metronomic chemotherapy. Metronomic capecitabine or CTX chemotherapy decreased vascular endothelial growth factor (VEGF) but elevated thrombospondin-1 (TSP-1) expression, reduced CEP levels and decreased microvessel density (MVD). These results indicated anti-angiogenesis may be correlated with the antitumor effects of metronomic capecitabine in colon cancer.
 ...
PMID:Anti-angiogenesis participates in antitumor effects of metronomic capecitabine on colon cancer. 2474 99

Recently, MET exon 14 deletion (METex14del) has been postulated to be one potential mechanism for MET protein overexpression. We screened for the presence of METex14del transcript by multiplexed fusion transcript analysis using nCounter assay followed by confirmation with quantitative reverse transcription PCR with correlation to MET protein expression by immunohistochemistry (IHC) and MET amplification by fluorescence in situ hybridization (FISH). We extracted RNAs from 230 patients enrolled onto the prospective molecular profiling clinical trial (NEXT-1) (NCT02141152) between November 2013 and August 2014. Thirteen METex14del cases were identified including 3 gastric cancer, 4 colon cancer, 5 non-small cell lung cancer, and one adenocarcinoma of unknown primary. Of these 13 METex14del cases, 11 were MET IHC 3+ and 2 were 2+. Only one out of the 13 METex14del cases was MET amplified (MET/CEP ratio > 2.0). Growths of two (gastric, colon) METex14del+ patient tumor derived cell lines were profoundly inhibited by both MET tyrosine kinase inhibitors and a monoclonal antibody targeting MET. In conclusion, METex14del is a unique molecular aberration present in gastrointestinal (GI) malignancies corresponding with overexpression of MET protein but rarely with MET amplification. Substantial growth inhibition of METex14del+ patient tumor derived cell lines by several MET targeting drugs strongly suggests METex14del is a potential actionable driver mutation in GI malignancies.
...
PMID:Gastrointestinal malignancies harbor actionable MET exon 14 deletions. 2637 39