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

To study etiology of gastric cancer, polymerase chain reaction-single sequence configuration polymorphism (PCR-SSCP) method was used to analyze the changes of P53 gene in gastric cancer tissues derived from areas with high prevalence of it. Changes in P53 gene occurreds in 45 of 90 specimens of gastric cancer tissues, and 39 of them showed focal mutation and six were deletion and insertion. Among the point mutation, 66.7% were substitution of A to G (G-A) or G to A (A-G), and only 15.5% were substitution of T to G (G-T) or G to T (T-G). These results suggest that there is a close relationship between P53 gene mutation and occurrence of gastric cancer. Based on the characteristics of base pair mutation, it is postulated that methylating carcinogen and polycyclic aromatic hydrocarbon from environment contributed to the above results.
 ...
PMID:[Analysis of types of P53 gene mutation in gastric cancer tissues]. 938 9

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.
 ...
PMID:Increase in proliferation and apoptosis of gastric epithelial cells early in the natural history of Helicobacter pylori infection. 940 20

In contrast to intrinsic drug resistance, induced multidrug resistance in gastric cancer cells has not been well studied. Therefore, two doxorubicin-resistant cell lines, (SNU-1DOX, SNU-16DOX), were derived in vitro from gastric carcinoma cell lines (SNU-1, SNU-16) respectively, and their characteristics were investigated. These resistances were not associated with overexpression of mdrl, multidrug resistance associated protein 1 (MRP1), pi or liver class of glutathione S transferase (GST pi, GSTL), heat shock protein 70 (HSP70), p53 or transglutaminase C (TGC). Levels of p21WAF1 RNA and topoisomerase II protein were decreased in the SNU-16DOX, but not in SNU-1DOX. However, the subsequent enzyme activity of topoisomerase II in SNU-16DOX was not decreased, but rather increased in SNU-16DOX. Furthermore, both resistant cell lines showed lower uptake and higher efflux of doxorubicin and induced cross-resistance to etoposide and vincristine in addition to doxorubicin, indicating a multi-drug resistance phenotype. In summary, we report two gastric carcinoma cell lines exhibiting induced multidrug resistance phenotype and suggest that mdrl, MRP1, GST, TGC, HSP70 and p53 do not play important roles in induced drug resistance in these cell lines. The role of changes in topoisomerase II activity and/or protein is still inconclusive, and p21WAF1 is associated with induced multidrug resistance in the SNU-16DOX gastric carcinoma cell line.
 ...
PMID:Characteristics of human gastric carcinoma cell lines with induced multidrug resistance. 941 98

To estimate the correlation between the expression of mutated p53 protein and the nuclear DNA ploidy of gastric cancer cells, as well as the influence of these factors on the prognosis of patients with advanced gastric cancer, we selected 161 patients with gastric cancer that had invaded the serosa and who were treated by potentially curative gastrectomy. The expression of p53 protein was detected in 95 (59%) patients and aneuploidy was detected in 70 (43.5%) patients. The percentage of tumors with DNA aneuploidy among the 95 tumors that were p53-positive was 51.6% and this percentage was significantly higher than that of tumors with DNA aneuploidy among the 66 tumors that were p53-negative (31.8%, P = 0.02). The percentage of cells in the G2M phase of the cell cycle was significantly higher in p53-positive tumors than that in p53-negative tumors (P = 0.024). The 161 patients were divided into four groups according to the expression of p53 protein and the DNA ploidy of their tumors. Patients with p53-positive tumors and DNA aneuploidy were allocated to group A (n = 49), patients with p53-positive tumors and DNA diploidy were allocated to group B (n = 46), patients with p53-negative tumors and DNA aneuploidy were allocated to group C (n = 21), and patients with p53-negative tumors and DNA diploidy were allocated to group D (n = 45). The 5-year survival rate of group D was 73.7% and it was significantly higher than that of group A (41.8%, P = 0.007). These observations indicate that mutated p53 protein might accelerate cell proliferation. Moreover, analysis of both p53 status and DNA ploidy of tumors seems to provide very important information for evaluation of the prognosis of patients with advanced gastric cancer.
 ...
PMID:The correlation between the expression of p53 protein and DNA ploidy in patients with gastric cancer that has invaded the serosa. 941 27

A total of 1664 patients with gastric cancer were examined to evaluate the rate of multiple synchronous primary tumours. In cases of multiple synchronous cancer (MSC), the tumours were analysed immunohistochemically for their expression pattern of p53, c-erbB2, ras, E-cadherin and proliferative activity. Multiple synchronous gastric carcinomas (MSCs) were observed in 61 out of 1664 patients (3.7%), with a total of 134 carcinomas. In our series, early carcinoma was observed more frequently in MSC than in solitary cancers. The comparison of tumour stage in MSC and solitary tumours revealed that multiple early gastric cancers were significantly more often of type I (protruded type) and IIa (superficial elevated type) than solitary early cancer. Multiple advanced carcinomas were more often of a lower pT category than solitary advanced gastric cancer. Performing immunohistochemistry for p53, c-erbB2 and ras in 134 tumours with MSCs, we observed positivity rates of 33%, 59% and 87% respectively. In 43 patients, the multiple tumours in each individual patient demonstrated an identical status of p53 and c-erbB2, and in 42 patients a similar pattern of E-cadherin expression was observed. The proliferative index, determined by proliferating cell nuclear antigen (PCNA) immunolabelling, did not differ significantly between the MSC in each patient. Ras immunostaining was detected in 53 out of 61 patients, but also in metaplasia and regenerative hyperplasia in the specimens. In survival analysis, no difference was observed between patients with solitary or multiple early or advanced carcinomas. Our results suggest that in at least a high proportion of patients with gastric cancer multiple primary tumours arise from precancerous conditions leading to similar genetic alterations.
 ...
PMID:Multiple simultaneous gastric carcinomas. 941 49

A series of 105 gastric cancer (GC) cases with paraffin-embedded specimens interviewed in a previous population-based case-control study conducted in a high-risk area around Florence, Italy, was examined for the presence of p53 mutations. Overall, 33 of 105 cases had a mutation (p53+) identified by single-strand conformational polymorphism and confirmed by sequencing (Y-H. Shiao et al., submitted for publication). p53+ cases had a more traditional dietary pattern (i.e., corn meal mush, meat soup, and other homemade dishes) and reported less frequent consumption of raw vegetables (particularly lettuce and raw carrots). A positive association with a high nitrite intake and a negative association with raw vegetables and diffuse type histology persisted in a multivariate analysis. In addition, p53+ cases tended to be located in the upper portion of the stomach and to be associated with advanced age and blood group A. No relation was found between the presence of p53 mutations and histologically defined Helicobacter pylori infection, smoking history, family history of gastric cancer, education, and social class. Of the 33 p53+ cases, 19 had G:C-->A:T transitions at CpG sites. These tumors tended to occur in females and in association with H. pylori infection but not other risk factors. The remaining 14 cases with a p53 mutation had mainly transversions but also two deletions and two transitions at non-CpG sites. These tumors showed a strong positive association with a traditional dietary pattern and with the estimated intake of selected nutrients (nitrite, protein, and fat, particularly from animal sources). The findings of this case-case analysis suggest that p53 mutations at non-CpG sites are related to exposure to alkylating compounds from diet, whereas p53 mutations at CpG sites might be related to H. pylori infection.
 ...
PMID:Diet, Helicobacter pylori, and p53 mutations in gastric cancer: a molecular epidemiology study in Italy. 941 4

For evaluation of the prognostic relevance of p53 expression in gastric cancer, the immunohistochemical tissue status of 133 primary gastric cancer patients was investigated for p53 expression and the association between p53 tissue status and clinicopathological parameters was analyzed. P53 immunoreactivity was detected in the nuclei of cancer cells in 35 cases (26.3%). The nuclear p53 immunoreaction was closely associated with tumor location, lymph node metastasis, and curability. Tumors with positive p53 stain reactions frequently metastasized to lymph nodes (metastatic rate: 91.4%) in contrast to tumors with negative p53 stain reactivity (71.4%, P = 0.021). Immunohistochemical analysis of primary gastric cancer appears to be an accurate and simple method of screening for p53 expression. In combination with common prognostic parameters, determination of p53 tissue status might help to detect prognostically unfavorable subgroups of gastric cancer patients.
 ...
PMID:p53 expression in gastric cancer: clinicopathological correlation and prognostic significance. 944 Jun 20

The paper presents the results of study on polymorfisms of xenobiotic biotransformation enzymes (CYP1A1, glutathione S-transferase MI and N-acetyltransferase 2) and p53 tumor suppressor protein in patients with lung, stomach and intestine cancer. The frequency of CYP1A1-Val allele in all studied cancer groups was 3 to 5 times higher than in healthy control group. The carriers of homozygous glutathione S-transferase M1 gene deletion and slow acetylator phenotype were also of higher lung cancer risk. The substantial increase in slow acetylator phenotype frequency was shown also in the group of intestine cancer patients. The p53 Arg/Pro polymorphism study revealed the elevated frequency of Arg allele in lung and stomach cancer groups. The risk of lung cancer for the carriers of susceptible alleles depended on the age and smoking status of the patients. The results testify to a high possibility of studied polymorphic genes to be the markers of susceptibility to oncopathologies.
 ...
PMID:[Genes and enzymes of the xenobiotic-metabolizing system in cancer pathology]. 944 23

Capsaicin (CAP) has been known to inhibit some tumor development in vivo (J.J. Jang, S.H. Kim, T.K. Yun, Inhibitory effect of capsaicin on mouse lung tumor development, in vivo, J. Korean Med. Sci. 3 (1989) 49-53; J.J. Jang, K.J. Cho, Y.S. Lee, J.H. Bae, Different modifying responses of capsaicin in a wide-spectrum initiation model of F344 rat, J. Korean Med. 6 (1991) 31-36) [1,2] even though its mechanism of action is not well understood. The objectives of this study were to examine the effect of CAP on expression of tumor forming-related genes in a Korean stomach tumor cell, SNU-1. We used slot blot hybridization to investigate its effect on a wide spectrum of proto-oncogenes. It was found that CAP enhanced the transcripts of two proto-oncogenes (c-myc and c-Ha-ras) and tumor suppressor gene p53. While a low concentration of CAP (0.01 microM) did not significantly increase the level of p53 transcript in SNU-1, it did increase it by a factor of 3.5 at a 10 microM dose of CAP. Consequently, SNU-1 cells are sensitive to CAP in the overexpression of tumor suppressor gene, p53 and proto-oncogenes, c-myc and c-Ha-ras, but not those of c-erbB-2, c-jun and bcl-2 genes. Both cell death and DNA fragmentation were shown in SNU-1 cells with treatment of CAP. Our results suggest that CAP induces apoptotic cell death in human gastric cancer cells (SNU-1) in vitro which may be possibly mediated by the overexpression of p53 and/or c-myc genes. Because cell suicide is arguably the most potent natural defense against cancer, the correlation between the induction of apoptosis and the change of tumor forming-related gene expression after CAP treatment should be further studied in detail.
 ...
PMID:Capsaicin can alter the expression of tumor forming-related genes which might be followed by induction of apoptosis of a Korean stomach cancer cell line, SNU-1. 946 Oct 43

We examined the relationship between apoptosis and the progression of human gastric carcinoma. Studies were conducted on a total of 88 surgically removed stomachs, comprising 26 minute (less than 5 mm in diameter), 29 early (limited to the mucosal and submucosal layer) and 33 advanced carcinomas. Apoptotic cells were visualized by terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-digoxigenin nick end labelling (TUNEL). Serial sections were immunostained for p53 and Ki-67. The mean apoptotic indices (AI: percentage of TUNEL signal positive cells) of minute, early, and advanced carcinomas were 4.1 +/- 0.6, 3.8 +/- 1.2, and 4.0 +/- 1.2 in 46 well differentiated carcinomas, and 2.1 +/- 0.5, 2.7 +/- 0.9, and 2.2 +/- 1.1 in 42 poorly differentiated carcinomas, respectively. Similarly, the mean Ki-67 labelling indices (KI) were 39.2 +/- 7.8, 47.2 +/- 12.8, 52.6 +/- 13.1 in the former, and 35.0 +/- 9.3, 36.9 +/- 10.3, and 40.0 +/- 9.2 in the latter, respectively. Both mean AI and mean KI were significantly higher in well differentiated than in poorly differentiated carcinomas (P < 0.05). However, the value of mean AI did not differ among minute, early, and advanced carcinomas in either histological type, while KI increased gradually with tumour progression. The frequency of nuclear p53 expression did not differ among the three categories, implying that the gene mutation is an early event in gastric carcinogenesis. There was no statistical significance between nuclear p53 expression and mean AI. These results suggest that the progression of gastric cancer is defined by a gradual increase of proliferative activity and constant occurrence of apoptosis and that naturally occurring apoptosis is induced predominantly via a p53-gene-independent pathway.
 ...
PMID:Frequent occurrence of apoptosis is an early event in the oncogenesis of human gastric carcinoma. 946 86


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>