UMLS:C0699790 - FACTA Search

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Query: UMLS:C0699790 (colon cancer)
28,837 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hypermethylation of CpG islands in the promoter regions is an important mechanism to silence the expression of many important genes in cancer. The hypermethylation status is passed to the daughter cells through the methylation of the newly synthesized DNA strand by 5-cytosine DNA methyltransferase (DNMT). We report herein that (-)-epigallocatechin-3-gallate (EGCG), the major polyphenol from green tea, can inhibit DNMT activity and reactivate methylation-silenced genes in cancer cells. With nuclear extracts as the enzyme source and polydeoxyinosine-deoxycytosine as the substrate, EGCG dose-dependently inhibited DNMT activity, showing competitive inhibition with a K(i) of 6.89 microM. Studies with structural analogues of EGCG suggest the importance of D and B ring structures in the inhibitory activity. Molecular modeling studies also support this conclusion, and suggest that EGCG can form hydrogen bonds with Pro(1223), Glu(1265), Cys(1225), Ser(1229), and Arg(1309) in the catalytic pocket of DNMT. Treatment of human esophageal cancer KYSE 510 cells with 5-50 microM of EGCG for 12-144 h caused a concentration- and time-dependent reversal of hypermethylation of p16(INK4a), retinoic acid receptor beta (RARbeta), O(6)-methylguanine methyltransferase (MGMT), and human mutL homologue 1 (hMLH1) genes as determined by the appearance of the unmethylation-specific bands in PCR. This was accompanied by the expression of mRNA of these genes as determined by reverse transcription-PCR. The re-expression of RARbeta and hMLH1 proteins by EGCG was demonstrated by Western blot. Reactivation of some methylation-silenced genes by EGCG was also demonstrated in human colon cancer HT-29 cells, esophageal cancer KYSE 150 cells, and prostate cancer PC3 cells. The results demonstrate for the first time the inhibition of DNA methylation by a commonly consumed dietary constituent and suggest the potential use of EGCG for the prevention or reversal of related gene-silencing in the prevention of carcinogenesis.
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PMID:Tea polyphenol (-)-epigallocatechin-3-gallate inhibits DNA methyltransferase and reactivates methylation-silenced genes in cancer cell lines. 1463 67

Although their sensitivity is not high, SCC, TPA and IAP are useful for esophageal cancer. The sensitivity of CEA, CA 19-9, is relatively high, especially in well-differentiated adenocarcinoma of gastric cancer with lymph node metastasis. AFP is specific to liver metastasis from gastric cancer, and CA 125 is also specific to peritoneal dissemination. CA 72-4 and NCC-ST-439 are useful markers for advanced staging. CEA, CA 19-9, is useful for colon cancer, especially for predicting preoperative staging. Half-life and doubling time of tumor markers is useful in some cases for the evaluation of operation and chemotherapy. We showed our data concerning postoperative CEA and/or CA 19-9 monitoring after operation for gastric cancer in 120 recurrent patients. Positivities of CEA and CA 19-9 for recurrence were 65.8% and 85.0%, respectively, both of which were significantly higher than the preoperative sensitivities (28.3% and 45.0%, respectively). In most patients with high levels of preoperative CEA and/or CA 19-9, these tumor markers increased again at recurrence. Recurrent diseases were detected between 5 months after detection by diagnostic imagings and 12 months before detection by diagnostic imagings (mean of 3.1+/-3.6 months before detection by diagnostic imagings) and between 10 months after detection by diagnostic imagings and 13 months before detection by diagnostic imagings (mean 2.2+/-3.9 months before detection by diagnostic imagings) by CEA and CA 19-9 monitorings, respectively. These results suggest that CEA and/or CA 19-9 monitoring after operation was useful to predict the recurrence of gastric cancer, especially in almost all the patients with high preoperative levels of these markers.
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PMID:[Gastrointestinal cancer]. 1533 58

Autologous tumor cells stimulated with T lymphocytes (AuTL) were generated ex vivo from peripheral blood lymphocytes over a two-week co-culturing process with autologous tumor cells. These AuTLs were capable of lysing established tumor cell lines and may have a potential for efficacy as an adoptive immunotherapy (IT) in advanced and metastatic refractory cancer patients (pts). We investigated the feasibility of a combination of AuTL transfer and chemotherapy (ChT) based on the conventional conditioning regimen in order to take advantage by both the anticancer effects and reconstruction of antitumor immunity. Nineteen patients were enrolled in a pilot clinical trial. The two administrations of AuTL were given prior to chemotherapy (ChT) for one treatment cycle. The treatment was repeated at least for three cycles over a one-week interval. The conventional ChT regimen was based on the standard dosage. The pts consisted of 3 of gastric cancer, colon cancer, lung adenocarcinoma, respectively, 6 of esophageal cancer, and 2 of breast and pancreas carcinoma, respectively. AuTLs were administered 1x/2 weeks using direct injection or intraarterial infusion. The median duration of the treatment was over 11.5 months, and the median survival time was 14.8 months. Adverse events related to both the ChT and AuTL transfers at all dosages were minimal. Four of the 13 pts achieved major tumor responses (2 CR: complete regression and 2 PR: partial regression) in this study. Three pts showed progressive disease, and 6 pts had stable disease for over 90 days. PBMC were evaluated for cytokine production prior to the treatment and after 3 treatments. Two and one of 4 CR/PR pts had increased IFN-gamma and TNF-alpha production with no TGF-beta1 responses by their PBMC after 3 treatments, respectively. Two out of 6 pts who experienced stable disease after the treatment had high IFN-gamma and TNF-alpha responses and no TGF-beta1 or IL-4 response. TGF-beta1 and IL-4 secretion increased in parallel in 3 out of 3 pts that experienced progressive disease after the treatment. These data show that combination therapy of AuTL transfer and non-myeloablative ChT is a feasible option for patients with refractory advanced cancers without serious adverse events and without reducing Th1 cytokine responses in peripheral blood for most of the pts that responded to the treatment. According to each mechanism of IT and ChT, a more stringent evaluation of AuTL transfer combined with non-myeloablative ChT for various kinds of cancers should be performed to manage the immunodeficiency in the pts with advanced cancer and to improve the effect of antitumor AuTLs.
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PMID:[The repetitive immune cell transfer therapy combining non-myelosuppressive chemotherapy for patients with advanced and refractory cancer]. 1555 72

Autoantibodies are often detected in the patients with esophageal cancer. We applied serological analysis of recombinant cDNA expression libraries (SEREX) to a case of esophageal squamous cell carcinoma in order to identify tumor antigens. A cDNA library derived from an esophageal cancer cell line was bacterially expressed and screened for interaction with antibodies in five allogeneic sera of patients with esophageal squamous cell carcinoma. To examine the specific immunoreactivity of the antigens, sera from 16 more patients with esophageal squamous cell carcinoma, 16 patients with gastric cancer, 16 patients with colon cancer, 16 patients with breast cancer and 37 healthy volunteers were screened. We identified 11 independent cDNA clones that potentially encoded esophageal cancer tumor antigens. The identified cDNA clones were SURF1, HOOK2, CENP-F, ZIC2, hCLA-iso, Ki-1/57, enigma, HCA25a, SPK and two EST clones named LOC146223 and AGENCOURT_7565913. The sero-positive rates of antibodies against SURF1 (48%), LOC146223 (38%), HOOK2 (14%) and AGENCOURT_7565913 (14%) were significantly higher in esophageal cancer patients than in healthy controls. At least one of these antibodies was detected in 18 (86%) of 21 sera from esophageal cancer patients. A disease-specific humoral immune response against SURF1, LOC146223, HOOK2 or AGENCOURT_7565913 was observed in most patients with esophageal squamous cell carcinoma. Antibodies against these SEREX antigens may represent a pool of candidates for serum tumor markers of esophageal squamous cell carcinoma.
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PMID:Serological identification of tumor antigens of esophageal squamous cell carcinoma. 1558 27

Chemosensitivity is affected by molecular biological factors, including factors related to the induction of apoptosis and the activity of proliferation. We analyzed immunohistochemically the expression of p53, Bcl-2, and Ki-67 in various types of cancers and assessed the correlation between this expression and chemosensitivity. Moreover, we investigated whether the expression of these factors could be a useful predictor for the clinical response to chemotherapy. Study subjects comprised 63 preoperative patients with untreated malignant tumors (9 with esophageal cancer, 12 with stomach cancer, 12 with colon cancer, 16 with liver cancer, and 14 with breast cancer). Immunohistochemical staining (the labeled streptavidin biotin technique: LSAB method) was used to assess expression of p53 protein, Bcl-2 protein, and Ki-67. A chemosensitivity test was carried out with the histoculture drug response assay method using four drugs: mitomycin C, 5-fluorouracil, doxorubicin hydrochloride (ADM), and cisplatin (CDDP). Immunohistochemical studies for p53 were found to be useful for predicting chemosensitivity.
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PMID:Immunohistochemistry of p53, Bcl-2, and Ki-67 as predictors of chemosensitivity. 1590 38

Aberrant activation and upregulation of the Wnt pathway is a key feature of many cancers. Wnt antagonists have recently attracted wide attention. Wnt inhibitory factor-1 (WIF-1) is a secreted antagonist that can bind to Wnt proteins directly and inhibit Wnt signaling pathway. It has been reported that WIF-1 expression is down regulated in several solid tumors and that WIF-1 is silenced by promoter hypermethylation in lung and colorectal cancer. By using RT-PCR, bisulfite sequence analysis, and methylation-specific PCR, we analysed expression and methylation of WIF-1 in cancer cell lines and freshly resected cancer tissues of the esophagus, stomach, colorectum, and pancreas. Downregulation of WIF-1 mRNA expression was observed in 61 (91.0%) of 67 cancer cell lines, 16 (80.0%) of 20 esophageal, 23 (74.2%) of 31 gastric, 41 (82.0%) of 50 colorectal, and six (75.0%) of eight pancreatic cancer tissues. Downregulation of WIF-1 expression was also observed at protein level. No significant association between WIF-1 downregulation and clinicopathological characteristics was found, suggesting that downregulation of WIF-1 expression is an early event in carcinogenesis of these cancers. Indeed, downregulation of WIF-1 expression was observed in 32 (72.7%) of 44 colorectal adenoma tissues and 18 (78.2%) of 23 early mucosal or submucosal colorectal carcinoma tissues. CpG island hypermethylation in the WIF-1 promoter region correlated with downregulation of WIF-1 expression in cancer cell lines and tissues. Treatment with demethylating agent, 5-aza-2'-deoxycytidine (5-aza-dC), restored WIF-1 expression in cancer cell lines. A combined treatment of 5-aza-dC and a histone deacetylase inhibitor, trichostatinA, restored WIF-1 expression synergistically, indicating the role of cytosine methylation and histone deacetylation in the silencing of the WIF-1 gene. Transfection of the WIF-1 gene construct into TE-1 esophageal cancer cell lines or SW48 colon cancer cell lines lacking WIF-1 expression resulted in a significant inhibition on colony formation, cell proliferation, anchorage-independent growth in soft agar. TOPflash assay showed WIF-1 inhibits Wnt canonical signaling in these cell lines. These results suggest tumor suppressive function of WIF-1, due to its ability to inhibit Wnt signaling. Our results suggest that WIF-1 silencing due to promoter hypermethylation is an important mechanism underlying aberrant activation of the Wnt signaling pathway in carcinogenesis of the digestive organs. Modulation of the Wnt pathway, through reversal of WIF-1 silencing by demethylating agents, is a potential target for treatment and/or prevention of gastrointestinal cancers.
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PMID:Frequent epigenetic inactivation of Wnt inhibitory factor-1 in human gastrointestinal cancers. 1600 17

Subtotal esophagectomy and reconstruction with colonic interposition grafting is the usual surgical treatment for benign esophageal stricture and malignant esophageal cancer. While short-term complications are frequently reported, long-term complications are rare. Herein, we report a 57-year-old male, with a previous caustic injury to the esophagus who underwent subtotal esophagectomy and right colon grafting at age 18. He underwent left hemicolectomy for obstructive colon cancer at the splenic flexure at age 55, followed by resection of the interposed colon graft due to adenocarcinoma at age 57.
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PMID:Metachronous adenocarcinoma occurring at an esophageal colon graft. 1603 35

We evaluated the efficacy of radiofrequency ablation (RFA) therapy for 29 patients with 36 hepatocellular carcinoma (HCC) nodules and 16 patients with 38 metastatic hepatic nodules. The mean tumor size was 26.4 mm. The primary lesions of patients with metastatic liver tumors were 9 colon cancer, 2 rectal cancer, 2 breast cancer, 2 gastric cancer, and 1 esophageal cancer. All nodules were treated using a Cool-tip RFA system. US-guided RFA was performed for 44 nodules, CT-guided RFA for 24 nodules, and intra-operative US-guided RFA for 6 nodules. In a mean observation period of 13.5 months, the mean complete ablation rate and the mean distant recurrence rate were 83.3% and 30.6% for HCC and 65.8% and 31.6% for metastatic nodules, respectively. The mean complete ablation rate of HCC was significantly higher than that of metastatic nodules (p < 0.05). The mean complete ablation rates of both HCC and metastatic hepatic nodules 3 cm or smaller in diameter were significantly higher than those of both tumors larger than 3 cm in diameter (p < 0.05). The mean distant recurrence rate of HCC in patients who have multiple nodules was 62.5% and it was significantly higher than that in patients who have a single nodule (28.6%) (p < 0.05). The mean complete ablation rate of metastatic nodules by intra-operative US guided RFA was 100% and it was statistically higher than that by other image guided RFA (p < 0.05).
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PMID:[Radiofrequency ablation for hepatocellular carcinoma and liver metastases]. 1631 81

EFNA1, EFNA2, EFNA3, EFNA4, EFNA5, EFNB1, EFNB2 and EFNB3 are EFN family ligands for EPH family receptors. EFN/EPH signaling pathway networks with the WNT signaling pathway during embryogenesis, tissue regeneration, and carcinogenesis. Comparative genomics analyses on EFNB1, EFNB2 and EFNB3 were performed by using bioinformatics and human intelligence (humint). EFNB1 mRNA was expressed in human embryonic stem (ES) cells, neural tissues, diffuse type gastric cancer, pancreatic cancer, colon cancer, brain tumors and esophageal cancer, EFNB2 mRNA in human ES cells, neural tissues and colon cancer, EFNB3 mRNA in human ES cells, neural tissues, brain tumors, pancreatic cancer and colon cancer. Because triple TCF/LEF-binding sites were identified within the 5'-promoter region of human EFNB3 gene, comparative genomics analyses on EFNB3 orthologs were further performed. Chimpanzee EFNB3 gene, consisting of five exons, was identified within AC164921.3 genome sequence. AY421228.1 was not a correct coding sequence for chimpanzee EFNB3. Chimpanzee EFNB3 gene was found to encode a 340-amino-acid protein showing 99.4% and 96.6% total-amino-acid identity with human EFNB3 and mouse Efnb3, respectively. Three TCF/LEF-binding sites within human EFNB3 promoter were conserved in chimpanzee EFNB3 promoter, and the second TCF/LEF-binding site in rodent Efnb3 promoters. CpG hypermethylation of EFNB3 promoter with 63.2% GC content as well as deletion of EFNB3 gene closely linked to TP53 tumor suppressor gene at human chromosome 17p13.1 should be investigated to elucidate the mechanism of infrequent EFNB3 upregulation in human colorectal cancer. EFNB3, identified as potential transcriptional target of WNT/beta-catenin signaling pathway, is a pharmacogenomics target in the fields of regenerative medicine and oncology.
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PMID:Comparative integromics on Ephrin family. 1659 16

Overexpression of cyclooxygenase-2 (Cox-2) is thought to exert antiapoptotic effects in cancer. Here we show that the tumor suppressor p53 upregulated Cox-2 in esophageal and colon cancer cell lines by inducing the binding of nuclear factor-kappaB (NF-kappaB) to its response element in the COX-2 promoter. Inhibition of NF-kappaB prevented p53 induction of Cox-2 expression. Cooperation between p53 and NF-kappaB was required for activation of COX-2 promoter in response to daunomycin, a DNA-damaging agent. Pharmacological inhibition of Cox-2 enhanced apoptosis in response to daunomycin, in particular in cells containing active p53. In esophageal cancer, there was a correlation between Cox-2 expression and wild-type TP53 in Barrett's esophagus (BE) and in adenocarcinoma, but not in squamous cell carcinoma (P<0.01). These results suggest that p53 and NF-kappaB cooperate in upregulating Cox-2 expression, promoting cell survival in inflammatory precursor lesions such as BE.
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PMID:Transcriptional activation of cyclooxygenase-2 by tumor suppressor p53 requires nuclear factor-kappaB. 1668 57

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