Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0024623 (gastric cancer)
 36,219 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Loss of heterozygosity (LOH) occurring on various chromosomes has been described in the majority of human tumors and its targets are believed to be tumor suppressor genes. Although allelic deletion of the p53 gene (over 60%) has been frequently observed in gastric cancer, as well as in other human malignancies, LOH of other tumor suppressor genes is still discrepant in gastric cancer. To our knowledge, simultaneous analysis of LOH using PCR in adenomatous polyposis coli (APC), deleted in colon cancer (DCC), and retinoblastoma susceptibility (Rb) genes has not yet been reported in sporadic gastric cancer. We examined 21 advanced gastric cancers (12 intestinal type and 9 diffuse type) for LOH at the APC, DCC, and Rb loci using PCR. Inclusion of these tumor suppressor genes in the allelic deletions was directly ascertained by performing PCR at polymorphic sites within the genes. LOH occurred in 30% of informative cases at APC, in 27% of informative cases at DCC, and in 30% of informative cases at Rb. Thirty-three percent of tumors informative at all loci (fully informative) lost heterozygosity at all three loci. There were no significant differences among histologic types in the prevalence of LOH at any locus and no correlations between losses involving APC, DCC, and Rb genes. These data suggest that inactivation of APC, DCC, and Rb is involved in the development and progression of some human gastric cancers regardless of histologic type.
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PMID:Loss of heterozygosity of multiple tumor suppressor genes in human gastric cancers by polymerase chain reaction. 860 93

We examined for germ-line p53 mutations and microsatellite instability in three gastric cancer patients who had family histories of gastric cancer aggregation. Although no germ-line p53 mutation was detected in these three cases, the replication error (RER) phenotype was observed in two of them. One base deletion in the sequence of ten repeating adenines of the type II transforming growth factor-beta receptor gene was detected in one of these two cases. Furthermore, there were young patients of 50 years and downward in their families. Therefore, it is possible that inherited disorders in mismatch repair systems contribute to high susceptibility to gastric cancers in these families.
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PMID:Microsatellite instability in gastric cancer prone families. 861 21

Mutations of the p53 gene were investigated in 80 surgical specimens of primary gastric cancer by polymerase chain reaction single-strand conformation polymorphism (PCR-SSCP) analysis. Mutations were detected in 18 tumors (22.5%) and localized to exons 5, 7 and 8. Mutations did not follow a random distribution among different subtypes, but instead clustered in the group of papillary adenocarcinomas, in which 7/12 (58.3%) cases were mutated. Positivity for p53 mutation was significantly higher in intestinal-type (37.5%) than in diffuse-type carcinomas (12.5%). These results suggest that gene alterations of p53 are not rare and may participate in the carcinogenesis of intestinal-type carcinomas of the stomach. Twenty of 21 p53 mutations were represented by single nucleotide changes, mostly missense mutations (19 events) and one nonsense mutation. Transversional mutations constitute the majority of p53 mutations (65%) and only 20% of mutations show G:C to A:T transitions. It is possible that the etiologies of gastric cancer in different geographical areas are different.
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PMID:p53 mutations in gastric cancers from Taiwan. 862 Apr 28

Cell cycle regulators such as cyclins, cyclin-dependent kinases (cdks) and their inhibitors control the growth of cells. SDI1/CIP1/WAF1/p21 is a potent inhibitor of G1 cdks, whose expression is induced by wild-type p53. To elucidate the mechanism of growth inhibition by transforming growth factor beta 1 (TGFbeta 1), we examined the effect of TGFbeta 1 on the expression of p21, G1 cyclins and cdks by human gastric cancer cell lines. TGFbeta 1 induced p21 expression and subsequently suppressed cdk2 kinase activity, followed by a reduction in phosphorylation of the product of the retinoblastoma tumor suppressor gene in TMK-1 cells, which are responsive to TGFbeta 1. Coimmunoprecipitation analysis demonstrated that TGFbeta 1 increased the level of p21 protein present in complexes with cdk2. In contrast, TGFbeta 1 did not induce p21 in TGFbeta 1-resistant MKN-28 cells. TGFbeta 1 did not affect the levels of p53 mRNA and protein in TMK-1 and MKN-28 cells, which contain mutated p53 genes. These mutated p53 complementary DNAs, when overexpressed, failed to activate transcription from the p21 promoter. Furthermore, TGFbeta 1 caused a reduction in the steady-state level of cyclin A protein concomitantly with inhibition of cdk2 kinase activity in TMK-1 cells. These results suggest that the growth inhibition of tumor cells by TGFbeta 1 is associated with p53-independent induction of p21, subsequent suppression of cdk activity and a decrease in cyclin A protein in TMK-1 cells.
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PMID:Inhibition of cell growth by transforming growth factor beta 1 is associated with p53-independent induction of p21 in gastric carcinoma cells. 864 69

We previously reported that introduction of the wild-type p53 gene into human cancer cells with deleted p53 enhanced apoptosis induced by chemotherapy [Fujiwara et al. (1994) Cancer Res 54:2287]. This suggests that p53 status could be a potent determinant of the therapeutic efficacy of DNA-damaging cancer therapy. We analyzed 24 patients with gastric or colorectal cancer for p53 mutations and apoptotic changes in surgical specimens. Out of 11 patients with gastric cancer, 3 were treated with chemotherapeutic drugs before resection; 5 of 13 patients with colorectal cancer had 30 Gy radiation prior to surgery. p53 mutations were detected in 4 cases of gastric cancer (36.4%) and in 6 cases of colorectal cancer (46.2%) by immunohistochemical staining. The preoperative DNA-damaging therapies increased the number of apoptotic cells in wild-type-p53-expressing tumors; tumors with mutant p53, however, significantly showed fewer apoptotic cells compared with those expressing wild-type p53. The p53-inducible WAF1/CIP1 protein was immunohistochemically observed in wild-type-p53-containing tumors, whereas mutant-p53-expressing tumors expressed no detectable WAF1/CIP1. Taken together, we conclude that p53 mutations are associated with the poor response of chemotherapy and radiotherapy.
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PMID:The p53 gene is a potent determinant of chemosensitivity and radiosensitivity in gastric and colorectal cancers. 864 47

This study examined p53 gene alterations in human gastric mucosa, intestinal metaplasia and well-differentiated (cohesive type) adenocarcinomas to clarify to the role of the p53 gene in gastric tumorigenesis by means of fluorescence in situ hybridization (FISH), polymerase-chain-reaction-single-strand-conformation polymorphism (PCR-SSCP) and immunohistochemistry. Gene alterations were compared with numerical changes of chromosome 17. Samples were obtained from 31 surgically resected stomachs affected with gastric cancer. There was no nuclear p53 protein in cells from normal gastric mucosa. Among 23 specimens of intestinal metaplasia, cells with p53 protein were variably detected in 5 incomplete metaplasias (colonic type). A histological study revealed a mildly dysplastic appearance. PCR-SSCP identified p53-gene mutation in exons 5 and 8 in 2 of the 5 samples. Numerical aberrations of chromosome 17 and the p53 gene were undetectable both in normal mucosa and in intestinal metaplasia. Variable numbers of tumor cells contained p53 protein in 13 (54%) of 24 carcinomas, and PCR-SSCP revealed abnormal bands in 5 of them. Mutations were detected in exons 5, 7, 7, 7 and 8. FISH analysis demonstrated that 6 carcinomas emitted 3 or 4 signals for chromosome 17, and 7 gave one signal for the p53 gene in over 20% of the cells. Ten (77%) of 13 carcinomas examined by FISH appeared to show a p53-gene deletion.
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PMID:Numerical aberration and point mutation of p53 gene in human gastric intestinal metaplasia and well-differentiated adenocarcinoma: analysis by fluorescence in situ hybridization (FISH) and PCR-SSCP. 864 18

The time course of induction of SOS-like stress responses such as enhanced reactivation (ER) and enhanced mutagenesis (EM) has been investigated in UV-C-irradiated skin fibroblasts from a xeroderma pigmentosum (XP) family, using herpes simplex virus type 1 as a probe. Similar ER studies were performed in a Li-Fraumeni syndrome (LFS) family and in a family with a high incidence of breast, ovarian, and colon cancer. In two XP (complementation group B) patients, with a striking absence of skin tumors even at an age of >40 years, only induction of EM was observed, whereas ER was absent (XPER-). The ER- phenotype was inherited from the father, whereas cells from the mother exhibited normal expression of ER and EM. This suggests that the absence of ER is a hereditary trait that is not correlated with a repair-deficient phenotype. Abnormally high levels of ER were observed in UV-C-exposed skin fibroblasts from rive LFS patients. The inheritance of the ER response was studied in one LFS family. High levels of ER were observed only in cells derived from affected individuals carrying one mutated p53 allele, whereas cells from unaffected family members, carrying two wild-type p53 alleles, exhibited normal ER levels. This result shows that abnormally high levels of ER positively correlate with the occurrence of cancer in affected individuals from a LFS family. Interestingly, abnormally high levels of ER were observed in cells from afflicted as well as from unafflicted members of a family with a high incidence of breast, ovarian, colon, and stomach cancer. This suggests that these latter individuals have inherited a mutated, putative predisposing gene, resulting in abnormal expression of ER, but that cancer had not yet developed. The results indicate that the ER response can possibly be used as a prognostic marker to identify carriers in various hereditary cancer-prone syndromes at an early age.
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PMID:Inheritance of abnormal expression of SOS-like response in xeroderma pigmentosum and hereditary cancer-prone syndromes. 865 7

Alterations in the structure and function of oncogenes and tumor suppressor genes, as well as genetic instability at several other genetic foci may be responsible for stomach carcinogenesis. The particular combination of multiple gene changes found in gastric cancer differs depending on the two histological types, strongly indicating that different genetic pathways exist for well differentiated or intestinal type and poorly differentiated or diffuse type gastric cancers. In general, genetic instability, telomerase activity, CD44 abnormal transcripts, and p53 mutation, all of which are common events of two types of gastric cancer, may be involved mainly in the early stage of stomach carcinogenesis, whereas activation of oncogenes and overexpression of the epidermal growth factor-related growth factor system may chiefly confer progression on gastric cancer. A new strategy of molecular diagnosis of gastrointestinal cancer, which has been implemented as a routine service in the Hiroshima University Clinical Laboratory, may provide new opportunities for early cancer diagnosis and more accurate evaluation of prognosis or grade of malignancy.
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PMID:Molecular biological observations in gastric cancer. 865 14

The prognostic value of overexpression of the p53-encoded protein was evaluated in 242 patients with gastric cancer. Formalin-fixed paraffin-embedded specimens of gastric adenocarcinomas were stained with the monoclonal antibody DO-7. 95 patients (39%) showed a high level of immunoreactivity (> or = 20% of cell nuclei staining positively), suggesting the presence of a mutation in the TP53 coding sequence. Overexpression of the p53 protein correlated significantly with stage of disease (P = 0.01), the presence of distant metastases (P = 0.04) and with the intestinal type of cancer (P = 0.04). No correlation between p53 overexpression and age, gender or the presence of the lymph node metastases was found. In univariate analysis, p53 immunoreactivity correlated significantly with survival (P = 0.0005). The median survival in the p53 high-level group was 19 months compared with 65 months in the p53 low-level group. In multivariate analyses, stage of disease and the presence of distant metastases emerged as independent prognostic factors, whereas p53 immunoreactivity did not (P = 0.08). The present results indicate that overexpression of the p53 protein is not an independent prognostic factor in patients with gastric cancer.
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PMID:Expression of p53 protein as a prognostic factor in patients with gastric cancer. 866 30

The investigation of molecular evidence of gastric carcinoma will be contributable to the prevention, gene diagnosis and therapy of human gastric neoplasms. To determine the specific genetic change in human gastric cancer (HGC) and precancerous lesions, we analysized FISH, PCR/SSCP, IHC and DNA sequencing by using multiple probes to detect the gene abnormalities (mutation, deletion, amplification or overexpression of genes) of 67 fresh tumors, 63 endoscopic biopsies including 30 dysplasia (DYS) and 33 intestinal metaplasia (IM, and 4 tumor cell lines from HGC patients. Multiple genetic abnormalities including hypomethylation of H-ras gene, amplification and overexpression of met and erbB2, deletion of APC, mts1/p16, p53 and nm23 gene and point mutation of p53 gene were noted in HGC and precancerous lesion of human gastric mucosa. Among these changes, p53 gene was the highest frequence genetic alteration in 39/67 (54-58%) of gastric carcinoma. These results indicate that overexpression of met and H-ras occurs at early stage in progression of neoplasia, amplification of met, erbB2 and akt2 gene occurs at progressing stage of tumorigenesis, deletion of p53, APC, mts1/p16 and nm23 occurs at advanced stage in the progression of cancer. The abnormalities should be associated with malignant phenotypes: poor differentiation, vascular invasion, lymph nodes metastasis, and low survival time. We detected p53 gene mutation in both cancer and precancerous lesions of IM and DYS. These results suggest that p53 may be a susceptible gene and alteration of p53 gene plays an important role in the development of HGC.
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PMID:[Multiple gene alterations involved in the processor of human gastric carcinogenesis]. 869 90


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