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)

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

The relationship between ras activation and over expression of p21 protein and DNA content in progression from benign to malignant of gastric mucosa was studied. The point mutation at 12 of c-Ha-ras oncogene was detected with PCR and specific oligonucleotide probe hybridization, the expression of ras p21 and DNA ploidy by flow cytometry was also carried out simultaneously on 66 human gastric tissues with gastric cancer and precancerous lesions, some of the patients were followed up for 42 to 60 months. The results showed that: activation of ras oncogene and p21 overexpression may be involved in the early stages of gastric cancer; DNA aneuploidy may not help for the early diagnosis, but can be useful for the diagnosis of gastric cancer in pathology; gastric cancer with mutational activation at 12 of c-Ha-ras may has unfavourable future. It concluded that c-Ha-ras activation and p21 overexpression may be help to early diagnosis of gastric cancer in clinic.
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PMID:[Multiple analysis for the c-Ha-ras activation and DNA content in human gastric precancerous lesions]. 873 43

T-cells that recognize mutated p21 Ras are relevant to immune surveillance systems against cancer. We report here evidence that immune responses of a T-cell clone recognizing mutated p21 Ras can be augmented by an analog peptide. Using spleen cells from a gastric cancer patient, we established the CD4+ alpha beta Th1-like clone C27 that recognizes wild-type (3EYKLVVVGAGGVGKS17) and mutated p21 Ras protein molecules and peptides, in an HLA-DR1-restricted manner. C27 responded prominently to mutated Ras peptides carrying Val or Ala at position 12, as compared to wild-type and other mutated peptides. C27 also exhibited a much stronger response to a mutated p21 Ras whole-protein molecule-carrying Val at position 12, as compared with the wild-type protein. The proliferative response and production of GM-CSF, TNF-alpha, and IFN-gamma by C27 were further augmented by replacing the possible first DR anchor 4Tyr of the mutated Ras peptide with Trp, a more potent anchor residue for the DR1 molecule. Enhancement of peptide antigenicity by substituting the HLA anchor residue of an antigenic peptide recognized by tumor-reactive T-cells may prove to be a novel strategy for antigen-specific cancer immunotherapy.
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PMID:Augmentation of immune response by an analog of the antigenic peptide in a human T-cell clone recognizing mutated Ras-derived peptides. 902 6

We examined the expression of p53, p21, cyclin D1, E, and PCNA in 75 cases of gastric cancer by immunohistochemical study and the expression of p21 RNA in cases by in situ hybridization. The rate of stage III, IV cases of p53(+) p21(-) group was significantly higher than that of any other groups. The apportinately 3-year survival rate of p53(+) p21(-) group was significantly lower than either that of p21(+) p53(-) or p53(-) p21(-) group. The 3-year survival rates of positive cases were significantly lower than those of negative cases on both cyclin D1 and E. The positive rate of cyclin E of the p53(-) p21(+) group was significantly lower than that of the p53(+) p21(-) group. The average PCNA Labeling. Index (LI) of the p53(+) p21(-) group was significantly higher than that of the p53(-) p21(+) group. The 3-year survival rate of cases with expression of p21 RNA was higher than that of cases without p21 RNA. Average PCNA L1 of cases with expression of mutant-type p53 was high and the number of poor prognostic cases in cases with expression of mutant-type p53 was large. In contrast, the average PCNA LI of cases with expression of p21 was low and the number of good prognostic cases with expression of p21 was large. These results suggest that p21 suppresses synthesis of DNA via cyclin E and PCNA.
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PMID:[The significance of p21 expression in gastric cancer]. 926 17

In this study, the expression of p21 protein was investigated immunohistochemically in 152 patients with gastric cancer. Expression of p21 was detected in 64 tumors (42.1%). There were significant differences among the expression of p21, histologic type, depth of invasion, lymph node metastasis, liver metastasis, and peritoneal metastasis. The deeper the tumor invaded, the more frequent p21 expression increased. Of the 152 patients, lymph node, liver and peritoneal metastasis were found in 86, 13 and 23 patients, respectively. p21 expression was more frequently lost in tumors from patients with metastasis. In relation to prognosis, patients with p21-positive tumors had a significantly better prognosis than those with p21-negative tumors. In conclusion, this study suggested that expression of p21 has a prognostic value in gastric cancer.
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PMID:[Immunohistochemical study of p21 expression in gastric carcinoma]. 926 18

Childhood acquisition of Helicobacter pylori is a critical risk factor for gastric cancer. Since tumorigenesis involves deregulation of proliferation and apoptosis, we examined gastric epithelial cell proliferation and apoptosis in H. pylori-infected children. Apoptosis and proliferation of gastric antral epithelial cells in biopsy specimens from patients with H. pylori-induced gastritis, secondary gastritis, and noninflamed controls were compared. p53 protein expression was examined immunohistochemically. Apoptotic cells were identified in the surface epithelium in each group. The apoptotic index was higher in specimens from patients with H. pylori gastritis (120 +/- 10) than secondary gastritis (50 +/- 10) and noninflamed controls (40 +/- 10, analysis of variance P < 0.005). Apoptosis decreased following H. pylori eradication and resolution of gastritis (P < 0.02). An expanded proliferative compartment was identified in H. pylori-induced gastritis (32.4 +/- 3.5; proliferative labeling index +/- SE) compared with secondary gastritis (18.9 +/- 2.8) and noninflamed controls (13.7 +/- 3.1, analysis of variance P < 0.01). The accelerated cell turnover was associated with p53 overexpression (analysis of variance P < 0.005). Accumulation of p53 was not associated with expression of the cyclin-dependent kinase inhibitor p21. The occurrence of altered cell turnover early in the natural history of chronic infection provides an explanation for the increased risk of gastric cancer development associated with childhood acquisition of infection.
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PMID:Increase in proliferation and apoptosis of gastric epithelial cells early in the natural history of Helicobacter pylori infection. 940 20

Gastric epithelial turnover increase in Helicobacter pylori infection has been demonstrated by interventional and non interventional methods for proliferating cell detection. We have observed a progressive hyperproliferation with the progression of Helicobacter pylori-induced mucosal lesions until the development of intestinal metaplasia. A similar result has been reported in other studies in the succession from normal mucosa to gastric carcinoma even if interventional techniques show less conspicuous differences in comparison to non interventional ones, which give an overestimated picture of proliferation. Later studies show that Helicobacter pylori-related hyperproliferation reverses after eradication. We have observed that this reversibility does not occur in areas of intestinal metaplasia, where the oncoprotein ras p21, involved in early gastric carcinogenesis, is expressed. This finding agrees with that demonstrating that hyperproliferation in intestinal metaplasia or gastric cancer is not affected by Helicobacter pylori. Other oncogenetic changes in intestinal metaplasia (i.e., p53 mutation) may further explain the persistently modified proliferative pattern of the epithelium. Recent studies suggest a lack of reversibility of intestinal metaplasia after Helicobacter pylori eradication, but this problem remains controversial. Our experience suggests that the persistence of the bacterium may increase the extent of this lesion. In conclusion the development of intestinal metaplasia is associated with an impaired regulation of gastric epithelial proliferation. Nevertheless, from the biological point of view, the progression towards carcinoma requires further DNA changes. Moreover, many questions need to be answered in order to establish clear guidelines for the clinical management.
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PMID:Effect of Helicobacter pylori eradication on intestinal metaplasia and gastric epithelium proliferation. 949 59

In a family consisting of 48 persons with high predisposition to familial stomach cancer (SCr), SCr was diagnosed in 8 persons (I-2; II-1,3,4; III-1,2,3,4). Moreover, one woman (III-8) had bilateral breast cancer and two (proband: IV-1 and her father's cousin: III-10) chronic gastritis. The proband, her father's cousin, his sister (III-11) and the proband's sister (IV-2) were examined clinically and cytogenetically (with the metaphase method on blood lymphocytes with G-banding of chromosome 21: (p12-pter) in 100% of cells on the basis of chromosomal instability; besides, the complex translocation in chromosome 2 in 4% of cells and the increase of q-arm of chromosome 21 was found in 2% of cells. The proband's sister (IV-2) had 3% of cells with polyploidy, the del 1 (p34-pter) in 1% of cells and the del 7 (p21-pter) in 4% of cells. The cytogenetic examination of the proband's uncle (III-10), carried out 3 times, revealed the case of the proband, endomitosis in 2% of cells, polyploidy in 2% of cells and hyperaneuploidy in 4% of cells. His sister (III-11) had 4% of cells with endomitosis, 3% of cells with chromosome and chromatid breaches, an increase of the p-arm of chromosome 21 in 100% of cells and the loss of 7p in 2% of cells. The nature of the phenomenon in chromosome 21 and the translocations in the members of this family is here discussed. The cytogenetic examination is currently ongoing.
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PMID:Medico-genetic and cytogenetic study of a family with high predisposition to malignant disease in gastro-intestinal tract. 950 10

To evaluate whether the expression of p53 and that of p21 are independent prognostic factors in patients with advanced gastric cancer, we investigated clinicopathological factors and the expression of p53 and p21 in 158 patients with gastric cancer that had invaded the serosa and who had undergone curative gastrectomy. In multivariate survival analysis of 156 surviving patients, we evaluated the size of the tumor, lymph node metastasis, venous invasion, lymph node dissection, expression of p53, and expression of p21 as independent prognostic factors. Moreover, we divided patients into four groups according to the expression of p53 and p21 in their tumors [group A, p53-/p21-, N = 40 (one died within 30 days of surgery); group B, p53-/p21+, N = 23; group C, p53+/p21-, N = 58; and group D, p53+/p21+, N = 37 (one died within 30 days of surgery)]. The 5- and 10-year survival rates of 39 patients in group A were 71.7% and 64.3%, those of 23 patients in group B were 81.4% and 81.4%, those of 58 patients in group C were 35.6% and 30.2%, and those of 36 patients in group D were 67.9% and 60.7%. The prognosis of patients in group C was poorer than that of patients in the other three groups. This result indicates that the evaluation of the expression of both p53 and p21 expression might provide prognostic information that is more accurate than that provided by evaluation of the expression of p53 alone.
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PMID:Expression of p53 and p21 are independent prognostic factors in patients with serosal invasion by gastric carcinoma. 959 Apr 8

Cultured human gastric cancer cell line PAMC82 was studied in vitro to further verify anti-tumor effect sof rare-earth elements and explore their mechanism of tumor inhibition. Inhibitory effects of elements lanthanum and cerium on cell growth, reverse effects of them on reduction of malignancy and effects of them on level of expression of oncogene and cancer suppressor gene were observed. Lanthanum chloride, cerium chloride and mixed rare-earth chloride at levels of 0.5 to 1.5 mmol/L could inhibit obviously growth of cancer cells and change cell morphology and microtubule structure of PAMC82, similar to that of normal cells, their colony-forming ability lowered in soft agar, and expression of tumor suppressor gene p53, p16 and p21 increased and that of gene nm23 lowered.
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PMID:[Effects of lanthanum and cerium on malignant proliferation and expression of tumor-related gene]. 981 84


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