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)

The chemosensitivity test for esophageal and gastric cancer cells collected by endoscopic biopsies before operation was investigated for evaluation by ATP assay. Experimentally, ATP assay was applied in human esophageal and gastric cancer cell line transplanted in nude mice. ATP level was measured by Lumiphotometer and showed positive linear correlation with the number of cancer cells in more than 10(3). Also ATP level increased when more than 10(3) cancer cells were cultured for more than 48 hours. On the other hand, more than 10(3) cancer cells were indicated to be collected by endoscopic biopsies, experimentally. Clinically, 7 specimens collected by endoscopic biopsy and 5 anticancer agents (MMC, CDDP, 5-FU, ADM and BLM) were used for the test. Forty-nine cases, 31 cases of esophageal cancer and 18 cases of gastric cancer were subjected to the study. The evaluability rates were 93.8%, respectively. Over-all predictive accuracy for esophageal cancer between the clinical responses and results of the assay was 72.0%. These results suggested the usefulness of biopsy specimens for the chemosensitivity test of anticancer agents.
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PMID:[The experiment and clinical evaluation of chemosensitivity test for esophageal and gastric cancer by ATP assay using endoscopic biopsy]. 151 5

This study was carried out to evaluate whether the preoperative levels of serum glycoproteins (CEA, SCC, TPA, IAP, ACT, ASP and sialic acid) and HLA antigens (class I and II) could be potential aids in the selection of suitable gastric and esophageal cancer patients for postoperative adjuvant immunotherapy of PSK. Gastric cancer patients underwent gastrectomy and received postoperative adjuvant chemotherapy (MMC, FT and ADR) with or without PSK. One hundred and forty esophageal cancer patients in cooperative study groups (organizing chairman; Dr. Hiroshi Satoh) underwent esophagectomy and received postoperative adjuvant radiotherapy and chemotherapy (FT, BLM) with or without PSK. The efficacy of PSK was recognized in the patients with normal levels of all glycoproteins in gastric cancer, and with normal levels of CEA or SCC or TPA and abnormal levels of one or more APRs in both gastric and esophageal cancer, and with positive HLA-B40 antigen. The combination of tumor-associated factors, such as CEA, SCC and TPA and various non-specific reactants such as APRs was useful as a prognostic indicator. In addition, some of HLA antigens were also valuable. The pretreatment levels of glycoproteins and HLA antigens have potential aids in the selection of patients with gastric and esophageal cancer for PSK treatment.
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PMID:[Clinical effects of PSK on esophageal and gastric cancer patients and usefulness of serum levels of glycoproteins and HLA antigens as prognostic indicators]. 258 37

Gastric cancer is one of the leading causes of cancer death worldwide, and although the incidence has decreased in Western countries, specific high-risk areas are present in Italy. Gastric cancer with high-level microsatellite instability (MSI-H) represents a well-defined subset of carcinomas showing distinctive clinicopathologic features. We examined clinicopathologic associations and long-term survival in a series of 159 gastric cancer cases from a high-risk population in Tuscany (central Italy). MSI-H was associated with antral location of the tumor (P = .001), intestinal type according to Lauren classification (P = .002), expanding type according to Ming classification (P = .0001), and mucinous histologic type according to the Japanese Research Society for Gastric Cancer classification (P = .002). In addition, MSI-H was strongly associated with a higher survival at 15 years (P = .01) and with loss of hMLH1 expression, evaluated by immunohistochemistry (P = .001). Multivariate analyses showed a significant association between the absence of hMLH1 reactivity and the expanding tumor type (P = .002). We also investigated the MSI-H-related genetic changes by analyzing coding repeats within target genes involved in pathways that control cell growth (TGFbetaRII, IGFIIR, RIZ, TCF4, DP2), apoptosis (BAX, BCL10, FAS, CASPASE5, APAF1), and DNA repair genes (hMSH6, hMSH3, MED1, RAD50, BLM, ATR, BRCA2, MRE11). Gastric cancer cases with MSI-H were found to accumulate heterozygous mutations affecting multiple molecular pathways and multiple genes within each pathway. Intriguingly, in this subset, TGFbetaRII mutations appeared to be inversely related to BLM mutations (P = .006), whereas RAD50 mutation carriers showed significantly reduced survival (P = .03).
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PMID:Gastric cancer with high-level microsatellite instability: target gene mutations, clinicopathologic features, and long-term survival. 1844 May 92

Gastric cancer is an aggressive cancer that is often diagnosed late. Early detection and treatment require a better understanding of the molecular pathology of the disease. The present study combined data on gene expression and regulatory levels (microRNA, methylation, copy number) with the aim of identifying key genes and pathways for gastric cancer. Data used in this study was retrieved from The Cancer Genomic Atlas. Differential analyses between gastric cancer and normal tissues were carried out using Limma. Copy number alterations were identified for tumor samples. Bimodal filtering of differentially expressed genes (DEGs) based on regulatory changes was performed to identify candidate genes. Protein-protein interaction networks for candidate genes were generated by Cytoscape software. Gene ontology and pathway analyses were performed, and disease-associated network was constructed using the Agilent literature search plugin on Cytoscape. In total, we identified 3602 DEGs, 251 differentially expressed microRNAs, 604 differential methylation-sites, and 52 copy number altered regions. Three groups of candidate genes controlled by different regulatory mechanisms were screened out. Interaction networks for candidate genes were constructed consisting of 415, 228, and 233 genes, respectively, all of which were enriched in cell cycle, P53 signaling, DNA replication, viral carcinogenesis, HTLV-1 infection, and progesterone mediated oocyte maturation pathways. Nine hub genes (SRC, KAT2B, NR3C1, CDK6, MCM2, PRKDC, BLM, CCNE1, PARK2) were identified that were presumed to be key regulators of the networks; seven of these were shown to be implicated in gastric cancer through disease-associated network construction. The genes and pathways identified in our study may play pivotal roles in gastric carcinogenesis and have clinical significance.
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PMID:Combining multi-dimensional data to identify key genes and pathways in gastric cancer. 2860 69

The main gene involved in gastric cancer (GC) predisposition is CDH1, the pathogenic variants of which are associated with diffuse-type gastric cancer (DGC) and lobular breast cancer (LBC). CDH1 only explains a fraction (10-50%) of patients suspected of DGC/LBC genetic predisposition. To identify novel susceptibility genes, thus improving the management of families at risk, we performed a multigene panel testing on selected patients. We searched for germline pathogenic variants in 94 cancer-related genes in 96 GC or LBC Italian patients with early-onset and/or family history of GC. We found CDH1 pathogenic variants in 10.4% of patients. In 11.5% of cases, we identified loss-of-function variants in BRCA1, BRCA2, PALB2, and ATM breast/ovarian cancer susceptibility genes, as well as in MSH2, PMS2, BMPR1A, PRF1, and BLM genes. In 78.1% of patients, we did not find any variants with clear-cut clinical significance; however, 37.3% of these cases harbored rare missense variants predicted to be damaging by bioinformatics tools. Multigene panel testing decreased the number of patients that would have otherwise remained genetically unexplained. Besides CDH1, our results demonstrated that GC pathogenic variants are distributed across a number of susceptibility genes and reinforced the emerging link between gastric and breast cancer predisposition.
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PMID:Multigene Panel Testing Increases the Number of Loci Associated with Gastric Cancer Predisposition. 3151 34

The BLM helicase protein plays a vital role in DNA replication and the maintenance of genomic integrity. Variation in the BLM helicase gene resulted in defects in the DNA repair mechanism and was reported to be associated with Bloom syndrome (BS) and cancer. Despite extensive investigation of helicase proteins in humans, no attempt has previously been made to comprehensively analyse the single nucleotide polymorphism (SNPs) of the BLM gene. In this study, a comprehensive analysis of SNPs on the BLM gene was performed to identify, characterize and validate the pathogenic SNPs using computational approaches. We obtained SNP data from the dbSNP database version 150 and mapped these data to the genomic coordinates of the "NM_000057.3" transcript expressing BLM helicase (P54132). There were 607 SNPs mapped to missense, 29 SNPs mapped to nonsense, and 19 SNPs mapped to 3'-UTR regions. Initially, we used many consensus tools of SIFT, PROVEAN, Condel, and PolyPhen-2, which together increased the accuracy of prediction and identified 18 highly pathogenic non-synonymous SNPs (nsSNPs) out of 607 SNPs. Subsequently, these 18 high-confidence pathogenic nsSNPs were analysed for BLM protein stability, structure-function relationships and disease associations using various bioinformatics tools. These 18 mutants of the BLM protein along with the native protein were further investigated using molecular dynamics simulations to examine the structural consequences of the mutations, which might reveal their malfunction and contribution to disease. In addition, 28 SNPs were predicted as "stop gained" nonsense SNPs and one SNP was predicted as "start lost". Two SNPs in the 3'UTR were found to abolish miRNA binding and thus may enhance the expression of BLM. Interestingly, we found that BLM mRNA overexpression is associated with different types of cancers. Further investigation showed that the dysregulation of BLM is associated with poor overall survival (OS) for lung and gastric cancer patients and hence led to the conclusion that BLM has the potential to be used as an important prognostic marker for the detection of lung and gastric cancer.
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PMID:Investigating the pathogenic SNPs in BLM helicase and their biological consequences by computational approach. 3270 57