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:2.7.7.49 (reverse transcriptase)
31,746 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Overexpression of the Eph receptor tyrosine kinases in cancers is related to malignant transformation, metastasis, tumor differentiation, and prognosis. Down-regulation of EphA7 secondary to hypermethylation has been reported in colorectal cancer. In the present study, expression of EphA7 in gastric cancer cell lines and gastric carcinoma specimens was determined by quantitative real-time reverse transcriptase-polymerase chain reaction. The expression of EphA7 was reduced in all tested gastric cancer cell lines; however, there is marked variability in expression among gastric carcinoma specimens. Overexpression was observed more often in younger patients (aged < or =65 years) (P = .03) and in patients with advanced cancer (P = .031). Hypermethylation of the EphA7 promoter-associated CpG island was found using methylation-specific polymerase chain reaction. Down-regulation of EphA7 was significantly related to hypermethylation (P = .001), and the level of hypermethylation was greater in moderately differentiated tumors than in poorly differentiated ones (P = .03). We also performed immunohistochemical staining for EphA7 in 52 gastric carcinoma specimens and found that expression of the protein was consistent with its transcript expression, with the protein being significantly overexpressed in younger patients (P = .016) and in patients with advanced tumors (P = .033). Our data indicate that EphA7 may have roles in the pathogenesis and development of gastric carcinomas.
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PMID:Differential expression of EphA7 receptor tyrosine kinase in gastric carcinoma. 1766 70

To determine the prognostic significance of the methods used to determine the presence of metastasis in second-tier lymph nodes of patients with gastric cancer, the authors studied lymph nodes surgically removed from 100 patients with gastric cancer (55 with early cancer, 45 with progressive). The results of HE staining were compared with those of immunohistochemistry using the anticytokeratin (CK) antibody and reverse transcriptase-polymerase chain reaction (RT-PCR) assays. Lymph node 7 or 8a was obtained intraoperatively, then mRNA was extracted using an immunobeads method, and RT-PCR with CK19 mRNA was performed. The P for Cox regression analysis for metastasis detected by HE staining, CK staining, and RT-PCR of all 100 cases was 0.312, 0.426, and 0.021, respectively, while for second-tier lymph nodes it was 0.154, 0.013, and 0.006, respectively. In conclusion, RT-PCR and CK staining for detection of metastasis in second-tier lymph nodes were more reliable prognostic indicators than conventional HE staining.
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PMID:Prognostic significance of gastric cancer metastasis in second-tier lymph nodes detected on reverse transcriptase-polymerase chain reaction and immunohistochemistry. 1806 40

Peritoneal dissemination is the most frequent recurrent type in advanced gastric cancer. Therefore, the early detection or prediction of peritoneal dissemination is important for the management of patients with advanced gastric cancer. Cytological examination with peritoneal lavage fluids obtained at surgery is widely used for the detection of peritoneal dissemination in gastric cancer. However, the sensitivity of the conventional method is not enough for the prediction of peritoneal recurrence. Recently, molecular diagnosis for detection of cancer cells has been widely studied as the sensitive method for detection of cancer micrometastasis in patients with malignancies including gastric cancer. In this study, novel genetic diagnosis with TRC (transcription reverse transcription concerted reaction) system for detection of carcinoembryonic antigen (CEA) mRNA (Tosoh corporation, Tokyo, Japan) has been introduced for peritoneal lavage diagnosis. We assessed the sensitivity and reproducibility of the test using the diluted gastric cancer cells. Furthermore, the results of TRC with peritoneal lavage fluids obtained from gastric cancer patients has been compared with results of conventional cytology and RT-PCR (reverse transcriptase-polymerase chain reaction).
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PMID:[Peritoneal lavage diagnosis with TRC (transcription reverse transcription concerted reaction) system for prediction of peritoneal recurrence in gastric cancer]. 1815 31

Complementary DNA microarrays have identified aberrantly expressed genes in patients with gastric cancer. One that encodes secretory leukocyte protease inhibitor (SLPI) is among the aberrantly expressed genes and is associated with metastasis in gastric cancers. We evaluated the potential of SLPI expression as a helpful biomarker for detection of gastric cancer. Tumor tissue and matching noncancerous mucosa were obtained from 60 patients immediately after gastric resection. SLPI expression levels were determined by Northern and Western blot tests and quantitative-reverse transcriptase-polymerase chain reaction (Q-RT-PCR). Paraffin-fixed tumor tissues were used for immunohistochemistry study in 119 patients. A consistent result was obtained between all examinations except plasma SLPI. SLPI mRNA transcripts and protein were overexpressed in gastric cancer cells, and the depth of wall invasion was significantly greater in serosa-invading (T3 and T4) cancers compared to the serosa-free (T1 and T2) cancers. These enhanced expressions were significantly associated with lymph node metastasis, and were significantly higher in stages III and IV, and higher than those in stages I and II. Five-year survival of patients with lower expression of the SLPI gene was significantly better than among patients with a higher expression. To better understand the function of SLPI in human gastric cancer cells, isogenic SLPI overexpressing cell lines (AZ521) were prepared. The migratory and invasive abilities were increased 4.4-fold to 6.9-fold, or 3.0-fold to 4.1-fold, respectively, in SLPI-overexpressing cell lines. The results point to SLPI as a potential prognostic marker for gastric cancer and its function in cell invasion.
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PMID:Overexpression of a secretory leukocyte protease inhibitor in human gastric cancer. 1868 58

We have analyzed the expression of Gastrokine 1 (GKN1), one of the most abundant protein of gastric mucosa, in Helicobacter pylori-related preneoplastic and neoplastic gastric lesions. The GKN1 expression was downregulated in 36 H. pylori-positive patients with respect to 29 H. pylori-negative subjects as evaluated by Western blot, reverse transcriptase polymerase chain reaction (RT-PCR) and immunohistochemistry, showing a progressive decrease from chronic gastritis to atrophy and intestinal metaplasia. Interestingly, in gastric cancer (GC) patients, GKN1 was undetectable in tissue tumoral areas but was instead expressed in the corresponding tissue non-tumoral areas. In conclusion our data suggests that GKN1 expression is related to the inflammatory damage of gastric mucosa and could be the related to the gastric cellular phenotype.
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PMID:Molecular expression of Gastrokine 1 in normal mucosa and in Helicobacter pylori-related preneoplastic and neoplastic gastric lesions. 1892 98

Urokinase-type plasminogen activator receptor (uPAR) plays a central role in the plasminogen activation cascade and participates in extracellular matrix degradation, cell migration and invasion. We evaluated the expression level of uPAR mRNA and the presence of isolated tumour cells (ITCs) in bone marrow (BM) and peripheral blood (PB) in gastric cancer patients and clarified its clinical significance. We assessed specific uPAR mRNA expression by quantitative real-time reverse transcriptase- polymerase chain reaction (RT-PCR) in BM and PB in 846 gastric cancer patients as well as three epithelial cell markers, carcinoembryonic antigen (CEA), cytokeratin (CK)-19 and CK-7. The uPAR mRNA expression in bone marrow and peripheral blood expressed significantly higher than normal controls (P<0.0001). The uPAR mRNA in BM showed concordant expression with the depth of tumour invasion, distant metastasis, and the postoperative recurrence (P=0.015, 0.044 and 0.010, respectively); whereas in PB, we observed more intimate significant association between uPAR expression and clinicopathologic variables, such as depth of tumour invasion, the distant metastasis, the venous invasion and the clinical stage (P=0.009, 0.002, 0.039 and 0.008, respectively). In addition, the uPAR mRNA expression in PB was an independent prognostic factor for distant metastasis by multivariate analysis. We disclosed that it was possible to identify high-risk patients for distant metastasis by measuring uPAR mRNA especially in peripheral blood at the timing of operation in gastric cancer patients.
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PMID:Expression of uPAR mRNA in peripheral blood is a favourite marker for metastasis in gastric cancer cases. 1905 Jul 4

In recent years, natural dietary agents have drawn a great deal of attention owing to their demonstrated ability to suppress cancer. We aimed to investigate the in-vitro gastric cancer preventive activity of a methanol extract obtained from table olives of Greek origin. Tested were AGS cell proliferation, induction of apoptosis and inhibition of inflammation. AGS stomach cancer cells were cultured at a density of 10 cells/ml. Methanol extract of olive was added to cultures at concentrations of 2.0, 1.6, 1.0, and 0.4 microg phenols/ml. Effect on cellular viability was evaluated via 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and percentages of early and late apoptotic cells were assayed by annexin V-FITC staining on a FACS scan. Interleukin-8 (IL-8) and intercellular adhesion molecule (ICAM)-1 mRNA and protein production were measured by applying reverse transcriptase-PCR and enzyme-linked immunosorbent assay. Olive extract significantly suppressed cell proliferation at 2.0, 1.6, and 1.0 microg phenols/ml. Flow cytometric analysis of Annexin-V labeled cells indicated that 2.0 microg phenols/ml significantly induced apoptosis. Similarly, at 2.0, 1.6, and 1.0 microg phenols/ml a significant decrease of ICAM-1 and IL-8 protein levels was observed. ICAM-1, as well as IL-8, mRNA expression were decreased in the presence of 2.0 microg phenols/ml. Results indicate that the methanol extract from olives, rich in phenolic compounds, exhibits gastric cancer preventive efficacy by limiting cell proliferation, inducing cell death and suppressing inflammation in AGS cells.
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PMID:In-vitro gastric cancer prevention by a polyphenol-rich extract from olives through induction of apoptosis. 1907 62

Prognosis of patients with undifferentiated gastric cancer is generally poor. The expression of various microRNAs (miRNAs) has not been comprehensively investigated in undifferentiated gastric cancer. Total RNA was extracted from the specimens of 42 undifferentiated gastric cancer tissues and paired normal gastric tissue. Quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) was performed for a set of 72 miRNAs. The expression of each miRNA relative to the internal control RNA was determined using the 2-DeltaCt method. The expression levels of 3 miRNAs (mir-34b, mir-34c and mir-128a) were significantly upregulated and those of 3 miRNAs (mir-128b, mir-129 and mir-148) were downregulated in undifferentiated gastric cancer tissue when compared with those of the paired normal tissues. The probability of survival was significantly lower in patients with high expression levels of mir-20b or 150. There was a correlation between mir-27a and lymph node metastasis. Our investigation provides a list of candidate miRNAs that may be associated with the prognosis in undifferentiated gastric cancer patients. Further study is warranted to identify the target genes of these miRNAs and their function.
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PMID:microRNA expression profile in undifferentiated gastric cancer. 1914 90

The structure and characteristics of the tumor vasculature are known to be different from those of normal vessels. Neuropilin2 (Nrp2), which is expressed in non-endothelial cell types, such as neuronal or cancer cells, functions as a receptor for both semaphorin and vascular endothelial growth factor (VEGF). After isolating tumor and normal endothelial cells from advanced gastric cancer tissue and normal gastric mucosa tissues, respectively, we identified genes that were differentially expressed in gastric tumor endothelial (TEC) and normal endothelial cells (NEC) using DNA oligomer chips. Using reverse transcriptase-PCR, we confirmed the chip results by showing that Nrp2 gene expression is significantly up-regulated in TEC. Genes that were found to be up-regulated in TEC were also observed to be up-regulated in human umbilical vein endothelial cells (HUVECs) that were co-cultured with gastric cancer cells. In addition, HUVECs co-cultured with gastric cancer cells showed an increased reactivity to VEGF-induced proliferation and migration. Moreover, overexpression of Nrp2 in HUVECs significantly enhanced the proliferation and migration induced by VEGF. Observation of an immunohistochemical analysis of various human tumor tissue arrays revealed that Nrp2 is highly expressed in the tumor vessel lining and to a lesser extent in normal tissue microvessels. From these results, we suggest that Nrp2 may function to increase the response to VEGF, which is more significant in TEC than in NEC given the differential expression, leading to gastric TEC with aggressive angiogenesis phenotypes.
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PMID:Neuropilin2 expressed in gastric cancer endothelial cells increases the proliferation and migration of endothelial cells in response to VEGF. 1940 92

The receptor tyrosine kinases (RTKs), epidermal growth factor receptor (EGFR) and vascular endothelial growth factor receptor 1-3 (VEGFR1-3), are frequently expressed in gastric cancer and are putative therapeutic targets in this disease. We have investigated the anti-proliferative and chemosensitizing properties of the multitargeted small-molecule RTK inhibitors sunitinib and vandetanib in a panel of 4 human gastric and esophageal cancer cell lines. In the 1st instance, the expression of potential targets of these small-molecule inhibitors was examined by reverse transcriptase-polymerase chain reaction, western blotting, and flow cytometry. EGFR mRNA and protein was detected in all cases, with VEGFR2 expression noted in all but 1 line. Both EGF and VEGF were shown to stimulate tumor cell growth, and both sunitinib and vandetanib were found to be associated with significant dose-dependent inhibition of proliferation and an enhancement of apoptosis, as determined by MTT and propidium iodide/Annexin V labeling assays, respectively. The addition of sunitinib to VEGF-stimulated NCI-N87 cells was associated with a reduction in MAPK phosphorylation (pMAPK) but not Akt phosphorylation (pAkt), whereas the addition of vandetanib was associated with reductions in both VEGF- and EGF-mediated VEGFR2 phosphorylation, pMAPK and pAkt. Co-administration of sunitinib significantly enhanced the sensitivity of MKN-45 cells to cisplatin and irinotecan. In addition, vandetanib synergistically enhanced the sunitinib-associated inhibition of gastric cancer cell growth. In conclusion, these preliminary data confirm the importance of EGFR and VEGFR signaling in gastric cancer and suggest that the simultaneous inhibition of RTK-pathways through sunitinib and vandetanib may provide therapeutic benefit in this disease.
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PMID:Analysis of anti-proliferative and chemosensitizing effects of sunitinib on human esophagogastric cancer cells: Synergistic interaction with vandetanib via inhibition of multi-receptor tyrosine kinase pathways. 2003 26


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