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)

Our previous study revealed that mutations of the p53 gene were detected by cDNA sequencing in one of four (25%) primary gastric tumors and in five of six (83%) gastric cancer cell lines. It was of interest that all five cell lines established from metastatic lesions had p53 gene mutations, while the single cell line established from a primary tumor lacked an abnormality. Thus, the current study was initiated to determine the frequency of p53 mutations in 10 pairs of samples from primary gastric carcinomas and their lymph node metastases, in addition to morphologically normal gastric mucosa. In addition, we correlated the findings with other relevant molecular markers including the metastasis associated nm23-H1 gene and loss of heterozygosity (LOH) using multiple polymorphic markers for chromosome 17p and sequencing the entire open reading frame (ORF) of the p53 gene. Five of ten (50%) patients were constitutionally heterozygous for one or more 17p and/or p53 probes (pYNZ 22, BamHI RFLP; pMct35.1, Mspl RFLP; php53cl, Bg/II RFLP), while none had LOH at the 17p and/or p53. A Bg/II RFLP for analysis of possible nm23-H1 somatic allelic deletion revealed no LOH out of four informative cases. One paired sample demonstrated the substitution of valine for isoleucine at codon 41 (GTT to ATT) in both primary gastric tumor and metastasis. Another metastatic sample demonstrated the substitution of proline for threonine at codon 278 (CCT to C/ACT) in addition to a non-mutated codon, while only the wild-type p53 sequence was present in the paired primary gastric tumor tissue.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Comparison of p53 gene mutations in paired primary and metastatic gastric tumor tissues. 790 5

A high serum alpha-fetoprotein (AFP) level was found in a patient with endometrial adenocarcinoma of the uterus, which appeared to be hepatoid on histological examination. The AFP of this unusual patient was purified by immunoaffinity chromatography and characterized. The electrophoretic profiles on sodium dodecyl sulfate-polyacrylamide get electrophoresis both before and after glycopeptidase F treatment were indistinguishable from those of a hepatoma AFP. This indicates that the patient's AFP was also composed of a single polypeptide chain of Mr 67,000 and an N-linked sugar chain of Mr 3,000. Amino acid sequence analyses of this AFP, and of AFP from hepatoma and umbilical cord serum indicated that the N-terminal sequences were essentially the same. The sequence, Arg-Thr-Leu-His-Arg-Asn-Glu-Tyr-Gly-Ile, was slightly different from previous reports, but matched that deduced from the cDNA sequence. AFP isoforms due to microheterogeneity of the sugar chain were analyzed by lectin affinity electrophoresis using a series of lectins. The AFP isoform profiles were distinct from those of proteins derived from cord serum, hepatoma, yolk sac tumor and gastric cancer. The reverse-transcription of RNA from the tumor tissue followed by a polymerase chain reaction using primers with AFP-specific sequences gave a product of the size and nucleotide sequence expected for AFP. mRNAs possessing the requisite sequences for albumin and transferrin syntheses were also detected in the tumor. The expression of these hepatocyte-specific proteins supported the hepatoid nature of this tumor.
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PMID:Biochemical characterization of alpha-fetoprotein and other serum proteins produced by a uterine endometrial adenocarcinoma. 876 25

Alterations of the HER-2 (erbB-2/neu) proto-oncogene have been associated with carcinogenesis and poor prognosis of certain cancers. A single nucleotide polymorphism (Ile/Val, A/G) in the transmembrane domain was reported to be associated with a risk of breast cancer. In our study, we examined the association between the HER-2 polymorphism and gastric carcinoma. The Ile/Ile, Ile/Val and Val/Val genotypes were found in 146 (68.9%), 56 (26.4%) and 10 (4.7%) of 212 gastric cancer patients and in 234 (81.5%), 48 (16.7%) and 5 (1.8%) of 287 control subjects, respectively. The Ile/Val or Val/Val genotype was significantly more frequent in patients than in controls (p = 0.005 and 0.033, respectively). The OR of Val/Val genotype then revealed a significantly enhanced risk of 3.25 (95% CI 1.09-9.70) compared to Ile/Ile genotype; heterozygous Ile/Val genotype showed an intermediate risk of 1.97 (1.27-3.06). In patients, carcinomas of advanced stage were significantly more frequent in patients with Ile/Val or Val/Val genotype than those with Ile/Ile genotype (p < 0.001). The logistic regression analysis for tumor invasion, lymph node metastasis and distant metastasis revealed that lymph node metastasis was most closely associated with the HER-2 genotype. These results suggest that this nucleotide polymorphism in the transmembrane domain-coding region of HER-2 could be associated with development of gastric carcinoma and may serve as a predictor of risk for a malignant phenotype of gastric cancer. The association of HER-2 genotype with clinicopathologic characteristics of gastric cancer was also suggested, which has to be confirmed with a larger sample size.
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PMID:A single nucleotide polymorphism in the transmembrane domain coding region of HER-2 is associated with development and malignant phenotype of gastric cancer. 1452 Jun 97

To evaluate the predictive value of a panel of gene polymorphisms involved in metabolism of 5-FU and cisplatin on clinical outcome in advanced gastric cancer patients. A total of 52 patients were enrolled in this study. DNA was extracted from paraffin-embedded tumour specimen. Genotypes were determined using PCR-RFLP. Median survival time was 6.0 months (95% CI 3.9;8.1). Overall response rate was 26%. Patients possessing the glutathione S-transferase P1-105 Valine/Valine (GSTP1-105VV) genotype showed a response rate of 67% compared to 21% in patients harbouring at least one GSTP1-105 Isoleucine (GSTP1-105I) allele (P=0.038). GSTP1-105VV patients demonstrated a significant superior median survival time of 15.0 months (95% CI 7.8;22.0) compared to 6.0 months (95% CI 5.1;7.0) in patients with at least one GSTP1-105I allele (P=0.037). Patients possessing a favourable thymidylate synthase (TS) genotype (2R/2R, 2R/3RC, 3RC/3RC) experienced a superior survival time of 10.2 months (95% CI 5.1;15.3) compared to 6.0 months (95% CI 5.0;7.0) in patients with unfavourable TS genotypes (P=0.099). Patients harbouring the GSTP1-105II genotype and one of the unfavourable TS genotypes showed an inferior median survival time of 6.0 months (95% CI 3.9;8.1) compared to 11 months (95% CI 6,23;15,77) in patients with either GSTP1-105VV or a favourable TS genotype (P=0.044). Testing for TS and GSTP1 polymorphisms may allow identification of gastric cancer patients who will benefit from 5-FU/cisplatin chemotherapy, sparing others the side effects of this chemotherapy.
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PMID:Polymorphisms of glutathione S-transferases (GST) and thymidylate synthase (TS)--novel predictors for response and survival in gastric cancer patients. 1704 83

Overexpression or amplification of the aurora kinase A (AURKA) gene induces chromosomal instability and transformation. AURKA SNPs are associated with several human cancers but their association with gastric cancer has yet to be investigated. In this study, 501 gastric cancer patients and 427 controls were genotyped for two coding SNPs in AURKA, 91A>T (31Ile>Phe) and 169G>A (57Val>Ile). Allele or genotype association with gastric cancer susceptibility was not observed in comparisons between the patient and control samples. However, 169G/G genotype was significantly more frequent in advanced gastric cancers than in early gastric cancers (age/sex-adjusted OR=2.2, 95% CI=1.3-3.8, P=0.0042). Moreover, the elevated risk of gastric cancer progression was associated with 91T-169G (age/sex-adjusted OR=1.9, 95% CI=1.1-3.4, P=0.025) and 91A-169G (age/sex-adjusted OR=1.6, 95% CI=1.0-2.6, P=0.048) haplotypes, having approximately 2.5-fold higher kinase activity than 91T-169A haplotype. The results suggest that 169G>A in AURKA is associated with progression of gastric cancer by affecting relative kinase activities of AURKA variants.
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PMID:Functional polymorphism 57Val>Ile of aurora kinase A associated with increased risk of gastric cancer progression. 1641 66

The pathogenesis of gastroduodenal diseases is related to the diversity of Helicobacter pylori strains. CagA-positive strains are more likely to cause gastric cancer than CagA-negative strains. Based on EPIYA (Glu-Pro-Ile-Tyr-Ala) motifs at the carboxyl terminus corresponding to phosphorylation sites, H. pylori CagA is divided into East Asian CagA and Western CagA. The former type prevails in East Asia and is more closely associated with gastric cancer. The present study used full sequences of the cagA gene and CagA protein of 22 H. pylori strains in gastric cancer and peptic ulcer patients from Southern Vietnam to make a comparison of genetic homology among Vietnamese strains and between them and other strains in East Asia. A phylogenetic tree was constructed based on full amino acid sequences of 22 Vietnamese strains in accordance with 54 references from around the world. The cagA gene was found in all Vietnamese H. pylori strains. Twenty-one of 22 (95.5%) strains belonged to the East Asian type and had similar characteristics of amino acid sequence at the carboxyl terminus to other strains from the East Asian region. From evidence of East Asian CagA and epidemiologic cancerous lesions in Vietnam, H. pylori-infected Vietnamese can be classified into a high-risk group for gastric cancer, but further studies on the interaction among environmental and virulence factors should be done. Finally, phylogenetic data support that there is a Japanese subtype in the Western CagA type.
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PMID:Diverse characteristics of the CagA gene of Helicobacter pylori strains collected from patients from southern vietnam with gastric cancer and peptic ulcer. 1984 30

Chronic Helicobacter pylori infection is known to be associated with the development of peptic ulcer, gastric cancer and gastric lymphoma. Currently, the bacterial factors of H. pylori are reported to be important in the development of gastroduodenal diseases. CagA protein, encoded by the cagA, is the best studied virulence factor of H. pylori. The pathogenic CagA protein contains a highly polymorphic Glu-Pro-Ile-Tyr-Ala (EPIYA) repeat region in the C-terminal. This repeat region is reported to be involved in the pathogenesis of gastroduodenal diseases. The segments containing EPIYA motifs have been designated as segments A, B, C, and D; however the classification and disease relation are still unclear. This study used 560 unique CagA sequences containing 1,796 EPIYA motifs collected from public resources, including 274 Western and 286 East Asian strains with clinical data obtained from 433 entries. Fifteen types of EPIYA or EPIYA-like sequences are defined. In addition to four previously reported major segment types, several minor segment types (e.g., segment B', B'') and more than 30 sequence types (e.g., ABC, ABD) were defined using our classification method. We confirm that the sequences from Western and East Asian strains contain segment C and D, respectively. We also confirm that strains with two EPIYA segment C have a greater chance of developing gastric cancer than those with one segment C. Our results shed light on the relationships between the types of CagAs, the country of origin of each sequence type, and the frequency of gastric disease.
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PMID:A comprehensive sequence and disease correlation analyses for the C-terminal region of CagA protein of Helicobacter pylori. 1989 42

The aim of this study was to evaluate the predictive value of the polymorphism Glutathione S-transferase P1 (GSTP1) Ile(105)Val on oxaliplatin/5-FU-based chemotherapy in advanced gastric cancer. Patients with advanced gastric cancer accepted oxaliplatin/5-FU-based chemotherapy as first-line chemotherapy were investigated. GSTP1 Ile(105)Val polymorphism was detected by TaqMan-MGB probe allelic discrimination method. Response to treatment was assessed by disease controlled rate. Time to progression, overall survival and toxicities were recorded. Final patient outcomes were as follows: the allele frequencies of GSTP1 were (105)Ile/(105)Ile 52%, (105)Ile/(105)Val 41% and (105)Val/(105)Val 7%. For patients with (105)Ile/(105)Ile and those with at least one (105)Val allele, disease control rate was 39% and 71% (P=0.026), respectively; median time to progression was 4.0 and 7.0 months (P=0.002); median overall survival time was 7.0 and 9.5 months (P=0.002). Neurological toxicity was more frequently occurred in patients with two (105)Ile alleles (P=0.005). In conclusion, patients with at least one (105)Val allele have better prognosis and response to oxaliplatin/5-FU-based regimen as first-line treatment for patients with advanced gastric cancer.
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PMID:Genetic polymorphism of GSTP1: prediction of clinical outcome to oxaliplatin/5-FU-based chemotherapy in advanced gastric cancer. 2051 4

The hMSH2 gene participates in DNA mismatch repair and its mutation can result in genetic instability of the human genome which is an important feature of tumorigenesis. In this study, genetic alterations of the hMSH2 gene were examined in 43 ovarian, 36 non-small cell lung (NSCL), 31 poorly differentiated gastric, 15 endometrial, and 11 colon cancers, nine gastric cancer cell lines, 41 adult T-cell leukemias (ATLs), two ATL cell lines, and 37 non-Hodgkin's lymphomas (NHLs), using polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) technique. Microsatellite instability (MSI) was also investigated for ovarian, NSCL, and colon cancers. The incidence of MSI was 1/36 (3%) for NSCL, 2/23 (9%) for ovarian, and 1/11 (9%) for colon cancers. Missense base changes of the hMSH2 gene were identified in two gastric cancer patients (ATG to ATA resulting in Met changing to Ile at codon 688 in exon 13 and ACA to GCA resulting in Thr changing to Ala at codon 803 in exon 14). These mutations were found in samples with no MSI. One ovarian and one gastric cancer, and six ATL samples showed two types of polymorphisms of hMSH2 (CTT to TTT resulting in Leu changing to Phe at codon 390 in exon 7 and CAG to AAG resulting in Gin to Arg at codon 419 in exon 7). Our data suggest that MSI and hMSH2 mutations are uncommon in sporadic tumors.
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PMID:Mutational analysis of the hMSH2 gene in a wide variety of tumors. 2152 33

Many bacterial pathogens inject into host cells effector proteins that are substrates for host tyrosine kinases such as Src and Abl family kinases. Phosphorylated effectors eventually subvert host cell signaling, aiding disease development. In the case of the gastric pathogen Helicobacter pylori, which is a major risk factor for the development of gastric cancer, the only known effector protein injected into host cells is the oncoprotein CagA. Here, we followed the hierarchic tyrosine phosphorylation of H. pylori CagA as a model system to study early effector phosphorylation processes. Translocated CagA is phosphorylated on Glu-Pro-Ile-Tyr-Ala (EPIYA) motifs EPIYA-A, EPIYA-B, and EPIYA-C in Western strains of H. pylori and EPIYA-A, EPIYA-B, and EPIYA-D in East Asian strains. We found that c-Src only phosphorylated EPIYA-C and EPIYA-D, whereas c-Abl phosphorylated EPIYA-A, EPIYA-B, EPIYA-C, and EPIYA-D. Further analysis revealed that CagA molecules were phosphorylated on 1 or 2 EPIYA motifs, but never simultaneously on 3 motifs. Furthermore, none of the phosphorylated EPIYA motifs alone was sufficient for inducing AGS cell scattering and elongation. The preferred combination of phosphorylated EPIYA motifs in Western strains was EPIYA-A and EPIYA-C, either across 2 CagA molecules or simultaneously on 1. Our study thus identifies a tightly regulated hierarchic phosphorylation model for CagA starting at EPIYA-C/D, followed by phosphorylation of EPIYA-A or EPIYA-B. These results provide insight for clinical H. pylori typing and clarify the role of phosphorylated bacterial effector proteins in pathogenesis.
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PMID:c-Src and c-Abl kinases control hierarchic phosphorylation and function of the CagA effector protein in Western and East Asian Helicobacter pylori strains. 2237 39


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