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

An experience with treatment of 58 patients operated upon for carcinoma of the colon complicated by acute intestinal obstruction and diastatic perforation has been analyzed, 13 patients had incomplete diastatic ruptures (tears) of the colon. In 23 patients the IV stage of the tumor process (remote metastases) were found and the other 35 patients had the III stage. In early terms after operation 37 (63.8%) patients out of 58 patients died. Lethality after incomplete diastatic ruptures of the colon made up 53.8%, and after diastatic perforation - 67.7%. The main cause of lethal outcomes was polyorganic insufficiency against the background of intoxication of mixed genesis (cancerous + endogenous). Ablation of colonic tumor is justified in cases of local peritonitis. Hemicolectomy with ablation of the diastatic rupture is indicated for the right-side localization of the tumor Obstructive resection is expedient for left-side localization of the tumor and rupture, the diastatic ruptures should be sutured or extraperitonized with application of cecostoma. Subtotal colectomy is possible for left-side localization of the tumor and diastatic ruptures of the right half of the colon. Symptomatic operations are indicated for canceromatosis of the peritoneum, terminal phase of peritonitis or infectious-toxic shock.
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PMID:[Experience in surgery of diastatic ruptures of the colon]. 1865 14

The guanine rich locations are present in human genome. Previous studies have shown that the presence of G rich sequences and motifs may be significant for gene activity and function. We decided to focus our interest to identify G rich motifs in promoters of oncogenes and tumor suppressor genes. We used a set of 100 most common oncogenes and tumor suppressor genes (TSG) for this analysis. We collected 600nt long promoters with -500 and +100 TSS (transcription start site) from the oncogenes and TSG set. Using a computer program, we calculated the G densities using numbers and locations of G forms with 100nt moving widow. We included G numbers from 2 to 7 guanines. Analysis shows that G density increases from -500 to +100 and more from TSS. G density is found to be maximum within -/+100 of TSS. The results of G densities were compared with the expression data of the selected oncogenes and tumor suppressor genes in patients with colon cancer (n=174).
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PMID:Detection of G-type density in promoter sequence of colon cancer oncogenes and tumor suppressor genes. 2622 89

Topoisomerase I-DNA-cleavage complexes (Top1cc) stabilized by camptothecin (CPT) have specific effects at transcriptional levels. We recently reported that Top1cc increase antisense transcript (aRNAs) levels at divergent CpG-island promoters and, transiently, DNA/RNA hybrids (R-loop) in nuclear and mitochondrial genomes of colon cancer HCT116 cells. However, the relationship between R-loops and aRNAs was not established. Here, we show that aRNAs can form R-loops in N-TERA-2 cells under physiological conditions, and that promoter-associated R-loops are somewhat increased and extended in length immediately upon cell exposure to CPT. In contrast, persistent Top1ccs reduce the majority of R-loops suggesting that CPT-accumulated aRNAs are not commonly involved in R-loops. The enhancement of aRNAs by Top1ccs is present both in human colon cancer HCT116 cells and WI38 fibroblasts suggesting a common response of cancer and normal cells. Although Top1ccs lead to DSB and DDR kinases activation, we do not detect a dependence of aRNA accumulation on ATM or DNA-PK activation. However, we showed that the cell response to persistent Top1ccs can involve an impairment of aRNA turnover rather than a higher synthesis rate. Finally, a genome-wide analysis shows that persistent Top1ccs also determine an accumulation of sense transcripts at 5'-end gene regions suggesting an increased occurrence of truncated transcripts. Taken together, the results indicate that Top1 may regulate transcription initiation by modulating RNA polymerase-generated negative supercoils, which can in turn favor R-loop formation at promoters, and that transcript accumulation at TSS is a response to persistent transcriptional stress by Top1 poisoning.
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PMID:Dynamic Effects of Topoisomerase I Inhibition on R-Loops and Short Transcripts at Active Promoters. 2678 95

KDM5c is a histone demethylase that specifically demethylates trimethylated and dimethylated H3 Lys-4 to play a central role in transcriptional repression. C-Jun is a proto-oncogene and promotes cell proliferation when ectopically accumulated, but can be ubiquitinated by SCF (FBXW7), leading to its degradation. FBXW7 is an E3 ubiquitin ligase of c-Jun, and exhibits carcinostasis in colon cancer. Here, we report that overexpression of KDM5c in human colon cancer cells results in attenuated FBXW7 transcription and accumulated c-Jun protein, leading to increased proliferation of colon cancer cells. We show that overexpression of KDM5c can result in increased c-Jun protein levels and decreased ubiquitin levels, with no significant change in mRNA levels of c-Jun. KDM5c overexpression blocks the ubiquitin-proteasome proteolytic pathway of c-Jun by down-regulating the expression of FBXW7. KDM5c down-regulation of FBXW7 occurs by demethylation of H3K4me3 at TSS and downstream of the FBXW7 gene. And interaction of KDM5c with H3K4me3 downstream of FBXW7 gene may be followed by recruitment of DNMT3b to methylate the spatially close CpG island located near the FBXW7 TSS. This methylation represses FBXW7 gene expression, which can reduce c-Jun degradation via the ubiquitin-proteasome pathway. TCGA database analysis revealed high expression of KDM5c in colon cancer tissues. KDM5c expression in colon cancer was correlated with poor overall survival of patients in the first 7 years. Data from TCGA showed that high expression of KDM5c was correlated with high DNA methylation of the FBXW7 gene, but was not positively correlated with methylation of the Jun gene. These results suggest that KDM5c regulation of colon cell proliferation is mainly mediated by the KDM5c-FBXW7-c-Jun axis.
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PMID:KDM5c Promotes Colon Cancer Cell Proliferation Through the FBXW7-c-Jun Regulatory Axis. 3304 30