Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.7.7.6 (RNA polymerase)
34,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Peritoneal dissemination is the most frequent type of recurrence in patients with gastric cancer with serosal exposure, irrespective of whether they have undergone curative gastrectomy. The purpose of this study was to establish a method to detect micrometastatic cells in the abdominal cavity and predict peritoneal recurrence in patients with such gastric carcinomas. A total of 86 patients with gastric carcinoma, undergoing gastrectomy, were examined. Reverse transcriptase-polymerase chain reaction (RT-PCR) assay was used to detect carcinoembryonic antigen (CEA) mRNA in abdominal lavage fluid. Twenty-four cases without serosal exposure were negative, while all 13 cases with macroscopic peritoneal dissemination were positive for CEA mRNA. Among the 49 cases with macroscopic serosal invasion and without peritoneal metastasis, cancer cells were detected in 27 cases with RT-PCR while in only 6 cases with conventional cytology. All cytologically-positive cases were also positive for CEA mRNA. Among the 27 CEA-positive cases, 15 patients (56%) relapsed with peritoneal metastasis within 12 months after gastrectomy. In contrast, none of the 22 CEA-negative cases had peritoneal recurrence within 16-60 months of observation, whereas in 43 cytologically-negative cases, 10 patients relapsed with peritoneal recurrence. As compared with conventional cytological examination, this method would be clinically more beneficial for detecting free cancer cells in the peritoneal cavity and for predicting peritoneal recurrence in gastric carcinoma with serosal invasion.
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PMID:Carcinoembryonic antigen mRNA in abdominal cavity as a useful predictor of peritoneal recurrence of gastric cancer with serosal exposure. 1263 1

Thrombospondin-1 (TSP-1) has been shown to play a role in angiogenesis in a variety of cancers, but some studies indicated a difference in the mechanism of TSP-1 on neovascularization according to organ or histological type. Wild-type p53 protein has been shown to induce TSP-1 expression. We examined the expression of TSP-1 protein in 80 gastric carcinomas using immunohistochemistry and studied the relationship with microvessel counts, p53 expression and clinicopathological factors. We also performed reverse-transcriptase polymerase chain reaction analysis for the TSP-1 mRNA expression in gastric carcinoma cell lines and gastric cancer tissue after laser capture microdissection. Strong expression of TSP-1 protein was detected in 30 (38%) of the 80 cases. Positive staining for TSP-1 was seen in the cytoplasm of the cancer cells. TSP-1 mRNA expression was confirmed in a majority of gastric carcinoma cell lines and carcinoma tissues. Microvessel counts were significantly higher in tumors with strong TSP-1 protein expression than in those without expression or weak expression of TSP-1 ( P=0.011). No significant correlation was found between TSP-1 expression and p53 staining and clinicopathological factors. Our results support an idea that increased TSP-1 expression may be associated with an angiogenic phenotype in gastric carcinoma and suggest that TSP-1 may play diverse roles in each organ.
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PMID:Expression of thrombospondin-1 is correlated with microvessel density in gastric carcinoma. 1271 77

Traditional Chinese medicinal plants are a treasure house for screening novel inhibitors of DNA polymerases and DNA topoisomerases from mammals; in the present study, nine lanostane-type triterpene acids were found in sclerotium of Poria cocos. Among the nine compounds, only dehydroebriconic acid could potently inhibit DNA topoisomerase II (topo II) activity (IC(50) = 4.6 microM), while the compound moderately inhibited the activities of DNA polymerases alpha, beta, gamma, delta, epsilon, eta, iota, kappa and lambda only from mammals, to similar extents. Another compound, dehydrotrametenonic acid, also showed moderate inhibitory effects against topo II (IC(50) = 37.5 microM) and weak effects against all the polymerases tested. Both compounds showed no inhibitory effect against topo I, higher plant (cauliflower) DNA polymerase I (alpha-like polymerase) or II (beta-like polymerase), calf thymus terminal deoxynucleotidyl transferase, human immunodeficiency virus type-1 reverse transcriptase, prokaryotic DNA polymerases such as the Klenow fragment of E. coli DNA polymerase I, Taq DNA polymerase and T4 DNA polymerase, or DNA metabolic enzymes such as T 7 RNA polymerase, T4 polynucleotide kinase and bovine deoxyribonuclease I. These findings suggest that dehydroebriconic acid and dehydrotrametenonic acid should be designated as topo II-preferential inhibitors, although they also moderately inhibited all the mammalian DNA polymerases tested. Both dehydrotrametenonic acid and dehydroebriconic acid could prevent the growth of human gastric cancer cells, and their LD(50) values were 63.6 and 38.4 microM, respectively. The cells were halted at the G1 phase in the cell cycle. The relation between the structure of triterpene acids and their inhibitory activities is discussed.
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PMID:A novel DNA topoisomerase inhibitor: dehydroebriconic acid, one of the lanostane-type triterpene acids from Poria cocos. 1507 95

The human kallikrein 12 (KLK12) gene is a new member of the KLK gene family, some members of which are implicated in the initiation and progression of cancer. In this study, we examined 50 non-cancerous tissues from Japanese patients with primary gastric cancer to determine the presence of genetic polymorphisms in the KLK12 gene using polymerase chain reaction (PCR)-single-strand conformation polymorphism and sequencing. Four different types of genetic polymorphisms were identified: one at a splice-donor site of intron 4 (c.457+2T>C), two in exon 6 (c.618_619delTG:p.Cys206fsX72 and c.735G>A:p.Met245Ile), and one in intron 3. The c.457+2T>C polymorphism was observed at a high frequency (allele frequency:0.63), compared to the frequencies of the two polymorphisms in exon 6 (allele frequency:0.01). Reverse transcriptase (RT)-PCR and Western blot analyses revealed that the c.457+2T>C polymorphism was associated with a splicing abnormality and that the expression of the human KLK12 protein (hK12), corresponding to the putative serine protease, was absent in individuals with a c.457+2C/C genotype but not in individuals with the T/T or T/C genotypes. We also found that recombinant His6-tagged hK12 has activity that cleaves chromogenic substrate (H-D-Pro-L-Phe-L-Arg-p-nitroaniline dihydrochloride), that is, serine protease activity. These results indicate that individuals with the c.457+2C/C genotype have no substantial expression of hK12 serine protease.
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PMID:Splice-site genetic polymorphism of the human kallikrein 12 (KLK12) gene correlates with no substantial expression of KLK12 protein having serine protease activity. 1530 Aug 58

Free cancer cells exfoliated from the serosal surfaces of primary cancers are considered to be responsible for peritoneal dissemination, which are both the most frequent pattern of treatment failure and the most important cause of death in gastric cancer patients. Detection of free cancer cells in the peritoneal cavity at the time of surgery, therefore, is thought to be of great value in predicting peritoneal recurrence and accordingly the prognosis of gastric cancer patients. This study was designed to determine whether free cancer cells in peritoneal lavage fluid from gastric cancer patients could be identified by a reverse-transcriptase polymerase chain reaction (RT-PCR) method specific to carcinoembryonic antigen (CEA) mRNA. Simultaneously, the results from conventional cytological examination were evaluated and the levels of CEA in peritoneal lavage were determined. Of the 40 gastric cancer patients enrolling in this investigation, 11 (27.5%) were positive for CEA mRNA in their peritoneal lavage, whereas only 6 (15%) and 8 (20%) were shown to be positive by cytological examination and peritoneal CEA (pCEA) assay, respectively. Furthermore, RT-PCR positive for CEA mRNA was correlated with the depth of tumor invasion (P<0.001), lymph node metastases (P=0.004), the TNM stage (P<0.001) and peritoneal recurrence (P<0.001). The technique of RT-PCR was more sensitive than conventional cytological examination and pCEA levels in the detection of peritoneal free cancer cells as well as in the prediction of peritoneal recurrence. In addition, CEA RT-PCR had a high concordance rate (82.5%) with the combination of cytology with pCEA levels. These observations suggest that it is feasible to identify free cancer cells in peritoneal lavage by using a CEA mRNA-specific RT-PCR method, and this assay can be a promising diagnostic modality for evaluating the risk of peritoneal dissemination in gastric cancer patients following operations.
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PMID:Gastric cancer cell detection in peritoneal lavage: RT-PCR for carcinoembryonic antigen transcripts versus the combined cytology with peritoneal carcinoembryonic antigen levels. 1589 Feb 45

Helicobacter pylori is an important risk factor of gastric cancer (GC). Although many H. pylori virulence factors have been reported, the pathogenic mechanism by which H. pylori infection causes GC remains unclear. The aims of this study were to identify GC-related antigens from H. pylori and characterize their roles in the development of GC. As GC and duodenal ulcer (DU) are considered clinically divergent, we compared two-dimensional immunoblots of an acid-glycine extract of H. pylori probed with serum samples from 15 patients with GC and 15 with DU to find GC-related antigens, which were subsequently identified by mass spectrometry. Many protein spots were recognized by more than one serum, and 24 of these were better recognized by GC sera. The proteins showing higher frequency of recognition in GC group are threonine synthase, rod shape-determining protein, S-adenosylmethionine synthetase, peptide chain release factor 1, DNA-directed RNA polymerase alpha subunit, co-chaperonin GroES (monomeric and dimeric forms), response regulator OmpR, and membrane fusion protein. Of these proteins, GroES was identified as a dominant GC-related antigen with a much higher seropositivity of GC samples (64.2%, n = 95) compared with 30.9% for gastritis (n = 94) and 35.5% for DU (n = 124). GroES seropositivity was more commonly associated with antral GC than with non-antral GC (odds ratio = 2.7; 95% confidence interval, 1.1-6.7). In peripheral blood mononuclear cells, GroES stimulated production of interleukin (IL)-8, IL-6, granulocyte macrophage colony-stimulating factor, IL-1beta, tumor necrosis factor-alpha, cyclooxygenase-2, and prostaglandin E(2). Moreover when incubated with gastric epithelial cells, GroES induced expression of IL-8, cell proliferation, and up-regulation of c-jun, c-fos, and cyclin D1 but caused down-regulation of p27(Kip1). We conclude that GroES of H. pylori is a novel GC-associated virulence factor and may contribute to gastric carcinogenesis via induction of inflammation and promotion of cell proliferation.
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PMID:Comparative immunoproteomics of identification and characterization of virulence factors from Helicobacter pylori related to gastric cancer. 1676 9

Early detection of disseminated tumor cells in the peripheral blood of patients with early stage gastric cancer could help to improve the outcome after tumor resection. The aim of this study is to evaluate the prognostic significance of tumor-related mRNA for the detection of circulating tumor cells in gastric cancer patients by a reverse-transcriptase polymerase chain reaction (RT-PCR) method. We simultaneously analyzed human telomerase reverse transcriptase (hTERT), cytokeratin-19 (CK-19), cytokeratin-20 (CK-20) and carcinoembryonic antigen (CEA) mRNA (messenger RNA) expression in the peripheral blood of 42 gastric cancer patients and 30 healthy individuals. Additionally, analyses were carried out for the correlation of these four molecular markers with patients' clinicopathologic features, as well as the occurrence of postoperative recurrence/metastasis. Among 42 gastric cancer patients, the prevalence of mRNA for hTERT, CK-19, CK-20, and CEA was 61.9% (26/42), 69% (29/42), 61.9% (26/42), and 78.6% (33/42), respectively. All 30 healthy individuals were negative for hTERT and CEA mRNA, while two were positive for either CK-19 mRNA or CK-20 mRNA. Positive CEA mRNA was significantly correlated with tumor size p=0.008), vessel invasion (p=0.001), depth of tumor invasion (p=0.007), lymph node metastasis (p< 0.001), and TNM stage (p<0.001). In addition, the multivariate logistic regression demonstrated that CEA mRNA expression was an independent and significant predictor for postoperative recurrence/metastasis (p=0.032). Our findings suggest that CEA mRNA may be a more reliable marker than hTERT, CK-19 and CK-20 for the detection of circulating cancer cells in gastric cancer patients' peripheral blood. Patients with positive CEA mRNA expression in peripheral blood have a significantly higher risk of postoperative recurrence/metastasis.
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PMID:Molecular detection of disseminated tumor cells in the peripheral blood of patients with gastric cancer: evaluation of their prognostic significance. 1678 43

Thymidylate synthase (TS), dihydropyrimidine dehydrogenase (DPD), thymidine phosphorylase (TP), and orotate phosphoribosyltransferase (OPRT) have been reported to be predictive parameters for the efficacy of fluoropyrimidine-based chemotherapy. mRNA expression of TS, DPD, TP, and OPRT were quantified by reverse-transcriptase polymerase chain reaction after harvesting cancer cells from 93 paraffin-embedded specimens of gastric cancer through laser capture microdissection. In vitro chemosensitivity testing by histoculture drug response assay was performed with surgically resected primary lesions of the same 93 patients. No significant correlation was observed between the mRNA expression and location of the tumor, histopathologic type, clinical stage, and other clinicopathologic variables, with the exception that OPRT mRNA had a weak correlation with drug sensitivity against 5FU (R=0.219, p=0.0343). OPRT was considered to have a major impact on drug sensitivity, although not sufficiently so to enable prediction of 5FU sensitivity solely based on the mRNA expression of this enzyme.
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PMID:Gene expression of 5-fluorouracil metabolic enzymes in primary gastric cancer: correlation with drug sensitivity against 5-fluorouracil. 1730 23

Gasdermin (GSDM or GSDMA), expressed in the upper gastrointestinal tract but frequently silenced in gastric cancers (GCs), regulates apoptosis of the gastric epithelium. It has three human homologs, GSDMB, GSDMC, and GSDMD (GSDM family) and they are considered to be involved in the regulation of epithelial apoptosis but not yet known. We investigated the expression pattern of the family genes in the upper gastrointestinal epithelium and cancers. Reverse transcriptase-polymerase chain reaction revealed that, unlike GSDMA expressed in differentiated cells, GSDMB is expressed in proliferating cells and GSDMD in differentiating cells. GSDMC, meanwhile, is expressed in both differentiating and differentiated cells. Colony formation assay showed that GSDMB, closely related to GSDMA, has no cell-growth inhibition activity in gastric cancer cells, and that GSDMC and GSDMD, respectively, exhibit the activity with different strengths from that of GSDMA. Expression analyses of the four family genes in esophageal and GCs suggested that GSDMC and GSDMD as well as GSDMA are tumor suppressors and that GSDMB, which was amplified and overexpressed in some GCs, could be an oncogene. The results of the expression analysis and colony formation assay suggest that each family gene may have a distinct function in the upper gastrointestinal epithelium.
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PMID:Distinctive expression and function of four GSDM family genes (GSDMA-D) in normal and malignant upper gastrointestinal epithelium. 1905 10

Epigenetic therapy using DNA methylation inhibitors and histone deacetylase (HDAC) inhibitors has clinical promise for the treatment of human malignancies. To investigate roles of microRNAs (miRNAs) on epigenetic therapy of gastric cancer, the miRNA expression profile was analysed in human gastric cancer cells treated with 5-aza-2'-deoxycytidine (5-Aza-CdR) and 4-phenylbutyric acid (PBA). miRNA microarray analysis shows that most of miRNAs activated by 5-Aza-CdR and PBA in gastric cancer cells are located at Alu repeats on chromosome 19. Analyses of chromatin modification show that DNA demethylation and HDAC inhibition at Alu repeats activates silenced miR-512-5p by RNA polymerase II. In addition, activation of miR-512-5p by epigenetic treatment induces suppression of Mcl-1, resulting in apoptosis of gastric cancer cells. These results suggest that chromatin remodeling at Alu repeats plays critical roles in the regulation of miRNA expression and that epigenetic activation of silenced Alu-associated miRNAs could be a novel therapeutic approach for gastric cancer.
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PMID:Chromatin remodeling at Alu repeats by epigenetic treatment activates silenced microRNA-512-5p with downregulation of Mcl-1 in human gastric cancer cells. 1950 96


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