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)

Thromboembolism frequently complicates gastric cancer. This study examined the solid phase interaction between gastric cancer and coagulation proteins in situ that may explain coagulation activation and that may contribute to tumor progression and angiogenesis in this tumor type. Immunohistochemical techniques were applied to tissues from 37 cases of adenocarcinoma of the stomach obtained at surgical resection. Fibrinogen was present throughout the tumor stroma. Fibrin and its D-dimer cross-link sites occurred at the host-tumor interface. Subunit "a" of factor (F) XIII and F VII, IX, X, and XII were observed on cancer cells. Prothrombin and prothrombin fragment F1+2 (F1+2) were demonstrated in the tumor stroma on cancer cells and on small blood vessels. Tissue factor (TF) was present on cancer cells and tumor-associated macrophages. Protein C was observed on cancer cells and small blood vessels, whereas protein S was present only in the vascular bed. There was no staining for tissue factor pathway inhibitor (TFPI). High-molecular-weight (HMW) urokinase plasminogen activator (u-PA) antigen was not detected, but weak and inconsistent staining for low-molecular-weight (LMW) u-PA was demonstrated on cancer cells. Weak staining for tissue plasminogen activator (t-PA) occurred on cancer cells and in the tumor stroma. In contrast, plasminogen activator inhibitor-1 (PAI-1) expression was strong in the tumor stroma, along with PAI-2 and PAI-3. The endothelium of small stromal blood vessels, particularly near the host-tumor interface, demonstrated von Willebrand factor antigen (vWF Ag). Vascular endothelial growth factor (VEGF) was present on cancer cells and stromal macrophages. These results demonstrate tumor cell-associated TF-dependent extravascular coagulation activation in situ in gastric cancer that does not appear to be counterbalanced by TFPI or sufficient fibrinolytic activity. Colocalization of VEGF with hemostatic proteins suggests that they may cooperate in the pathogenesis of gastric cancer.
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PMID:Tissue factor-dependent coagulation activation and impaired fibrinolysis in situ in gastric cancer. 1288 33

In order to assess the role of the changes of DCC and APC/MCC genes in the development and progression of gastric cancer, the loss of heterozygosity (LOH) of these genetic loci was investigated in 45 surgical specimens of gastric cancer with PCR-RFLP. The rate of LOH was 30.0% (9/30) at APC/MCC gene and 33.3% (15/45) at DCC gene. LOH was found in both intestinal and gastric types of gastric cancer and the rate of LOH of DCC gene was significantly higher in stages III to approximately IV gastric cancer (48.0%) than in stages I to approximately II (15.0%) (P<0.05). LOH of APC/MCC gene could be found in both early and advanced stages of gastric cancer. These findings suggest that changes of DCC and APC/MCC genes are involved in the development and progression of the intestinal and gastric types of gastric cancer.
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PMID:Study of loss of heterozygosity at DCC and APC/MCC genetic loci of gastric cancer. 1290 20

Topics discussed here include PTEN mutations and colonic polyps; WNT signaling, APC, beta-catenin, and gastrointestinal neoplasms; mismatch-repair genes (MLH1, MSH2, PMS1, MSH6) and hereditary nonpolyposis colorectal cancer; MYH mutations and autosomal recessive colorectal tumors; STK11 mutations and Peutz-Jeghers syndrome; TGFbeta and gastrointestinal cancer; BMPR1A mutations and juvenile polyposis; FGF/FGFR alterations in gastrointestinal neoplasms; PTCH mutations and gastrointestinal neoplasms; RUNX3 expression and gastric cancer; role of mucins in gastric carcinogenesis; KIT, PDGFRalpha, and gastrointestinal stromal tumors; intestinal neurofibromatosis; and gastrointestinal tumors in other disorders.
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PMID:Molecular dimensions of gastrointestinal tumors: some thoughts for digestion. 1451 68

Akt/protein kinase B (PKB) plays an important role in cell survival. However, the role of Akt in the biology of gastric cancer has not been well studied. We sought to investigate the expression of Akt or phosphorylated Akt (pAkt) in human gastric carcinomas and to analyze the relationship between Akt or pAkt and the clinicopathologic parameters. The expressions of Akt and pAkt were evaluated immunohistochemically in 311 gastric carcinomas using the tissue array method. Akt expression was detected in 74% of the tumors and pAkt expression in 78%. pAkt was highly expressed in the early stage of pTNM (p=0.011). We also found an inverse association between pAkt and lymphatic invasion (p=0.01) or lymph node metastasis (p=0.008). pAkt expression was significantly correlated with a higher survival in patients with stage I carcinomas (p=0.0003). Interestingly, combined evaluation revealed that the group with pAkt-positive and lymph node-negative carcinomas showed a better prognosis than the other groups (p<0.0001). In addition, pAkt was shown to correlate positively with APC (p=0.002) and Smad4 (p<0.0001) expression. These findings suggest that pAkt expression may help to predict the clinical outcome of gastric cancer patients.
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PMID:Akt/PKB activation in gastric carcinomas correlates with clinicopathologic variables and prognosis. 1467 19

A number of tumor suppressor and tumor-related genes exhibit promoter hypermethylation with resulting gene silencing in human cancers. In addition, several gene promoters have also been shown to become hypermethylated in non-neoplastic cells during aging. To assess the physiological consequence and clinical significance of gene promoter methylation in gastric epithelia, our laboratory has studied the methylation status of tumor suppressor and tumor-related genes, including APC, DAP-kinase, DCC, E-cadherin, GSTP1, hMLH1, p16, PTEN, RASSF1A, RUNX3 and TSLC1, in neoplastic and non-neoplastic gastric epithelia. The tumor suppressor and tumor-related genes, except APC, were generally unmethylated in non-neoplastic gastric epithelia obtained from younger individuals. The frequencies of methylation increased with age to varying degrees in various genes, although GSTP1 and PTEN methylation was completely absent in both neoplastic and non-neoplastic gastric epithelia. The methylation frequencies in each gene were found to be comparable in neoplastic and non-neoplastic gastric epithelia, except the methylation of RUNX3 and TSLC1, which was mostly cancer-specific (P<0.01). When methylation frequencies were compared between non-neoplastic gastric epithelia from cancer-bearing and non-cancer-bearing stomachs, hMLH1 and p16 methylation was more frequent in those from cancer-bearing stomachs (P<0.01). Promoter methylation in tumor suppressor and tumor-related genes initially occurs in non-neoplastic gastric epithelia, increases with age, and ultimately silences gene function to constitute a field-defect that may predispose tissues to gastric cancer evolution. In clinical applications RUNX3 and TSLC1 methylation may be utilized as molecular diagnostic markers, and hMLH1 and p16 methylation as predictors of malignancy in the stomach.
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PMID:Promoter methylation status of tumor suppressor and tumor-related genes in neoplastic and non-neoplastic gastric epithelia. 1470 90

Portal vein thrombosis (PVT) has rarely been documented in patients after splenectomy for gastric malignancy. We report a case of PVT that occurred after splenectomy as part of an en-bloc node dissection performed to treat gastric malignant lymphoma. A 38-year-old man underwent total gastrectomy and splenectomy with en-bloc D2 lymph node dissection. The spleen weighed 480 g. On postoperative day (POD) 31, the patient complained of abdominal pain in the right upper quadrant accompanied by fever. Moderate elevations of C-reactive protein (CRP), aspartate transaminase (AST), and alanine transaminase (ALT) were noted. Contrast-enhanced computed tomography (CT) and ultrasonography disclosed thrombus in the portal vein and the splenic vein. There were no abnormalities in the levels of lupus anticoagulant, protein C antigen, protein S antigen, or antithrombin III (AT III). A diagnosis of PVT was made, and prompt treatment, including intravenous heparin combined with tissue plasminogen activator (tPA) was initiated, followed by longterm warfarin. This treatment resulted in clinical improvement, but failed to achieve thrombolysis in the portal vein. At follow-up after 6 months, the patient complained of postprandial abdominal pain with persistent peripheral edema and ascites. This case indicates that splenectomy for en-bloc node dissection in gastric malignancy is a possible cause of PVT. Because both the symptoms and the laboratory data in PVT are nonspecific, a high level of clinical suspicion and a low threshold for obtaining imaging examinations are important in the early diagnosis of PVT. Surgeons should remember PVT among several other complications whenever patients treated with radical gastrectomies are symptomatic and imaging studies are considered necessary.
Gastric Cancer 2003
PMID:Portal vein thrombosis after splenectomy for gastric malignant lymphoma. 1471 20

Multiple genetic and epigenetic alterations in oncogenes, tumour-suppressor genes, cell-cycle regulators, cell adhesion molecules, DNA repair genes and genetic instability as well as telomerase activation are implicated in the multistep process of human stomach carcinogenesis. However, particular combinations of these alterations differ in the two histological types of gastric cancer, indicating that well-differentiated or intestinal-type and poorly differentiated or diffuse-type carcinomas have distinct carcinogenetic pathways. In the multistep process of well-differentiated-type carcinogenesis, the genetic pathway can be divided into three subpathways: an intestinal metaplasia-->adenoma-->carcinoma sequence, an intestinal metaplasia-->carcinoma sequence and de novo. In the multistep process of well-differentiated-type or intestinal-type gastric carcinogenesis, infection with Helicobacter pylori may be a strong trigger for hyperplasia of hTERT-positive 'stem cells' in intestinal metaplasia. Genetic instability and hyperplasia of hTERT-positive stem cells precede replication error at the D1S191 locus, DNA hypermethylation at the D17S5 locus, pS2 loss, RARbeta loss, CD44 abnormal transcripts and p53 mutation, all of which accumulate in at least 30% of incomplete intestinal metaplasias. All of these epigenetic and genetic alterations are common events in intestinal-type gastric cancer. An adenoma-->carcinoma sequence is found in about 20% of gastric adenomas with APC mutations. In addition to these events, p53 mutation and loss of heterozygosity (LOH), reduced p27 expression, cyclin E expression and the presence of c-met 6.0-kb transcripts allow malignant transformation from the above precancerous lesions to intestinal-type gastric cancer. DCC loss, APC mutations, 1q LOH, p27 loss, reduced tumour growth factor (TGF)-beta type I receptor expression, reduced nm23 expression and c-erbB gene amplification are frequently associated with an advanced stage of intestinal-type gastric cancer. The de-novo pathway for carcinogenesis of well-differentiated gastric cancer involves LOH and abnormal expression of the p73 gene that is responsible for the development of foveolar-type gastric cancers with pS2 expression. On the other hand, LOH at chromosome 17p, mutation or LOH of p53 and mutation or loss of E-cadherin are preferentially involved in the development of poorly differentiated gastric cancers. In addition to these changes, gene amplification of K-sam, and c-met and p27 loss as well as reduced nm23 obviously confer progression, metastasis and diffusely productive fibrosis. Mixed gastric carcinomas composed of well-differentiated and poorly differentiated components exhibit some but not all of the molecular events described so far for each of the two types of gastric cancer. Besides these genetic and epigenetic events, well-differentiated and poorly differentiated gastric cancers also organize different patterns of interplay between cancer cells and stromal cells through the growth factor/cytokine receptor system, which plays an important role in cell growth, apoptosis, morphogenesis, angiogenesis, progression and metastasis. Meta-analysis of epidemiological studies and animal models show that both intestinal and diffuse types of gastric cancer are equally associated with H. pylori infection. However, H. pylori infection may play a role only in the initial steps of gastric carcinogenesis. Differences in H. pylori strain, patient age, exogenous or endogenous carcinogens and genetic factors such as DNA polymorphism and genetic instability may be implicated in two distinct major genetic pathways for gastric carcinogenesis.
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PMID:Genetic pathways of two types of gastric cancer. 1505 5

Gastric carcinogenesis involves multiple genetic and epigenetic alterations. Epigenetic silencing of tumor-related genes due to CpG island methylation (CIM) has been recently reported in gastric cancer, but the role in precursor lesions is not well understood. We analysed the methylation status of the tumor suppressor gene p16, the DNA mismatch repair gene hMLH1, and four CpG islands (MINT1, MINT2, MINT25, and MINT31) using methylation-specific polymerase chain reaction in 35 polypoid adenomas and 46 flat dysplasias unassociated with carcinoma, 34 early adenocarcinomas (T1N0M0) and associated adenomas/dysplasias, and corresponding adjacent non-neoplastic mucosa. The extent of CIM was defined by the fraction of methylated loci (methylation index), and compared with previously characterized genetic alterations (microsatellite instability (MSI) and APC gene mutation). We found that methylation of p16 was more frequent in adenocarcinoma-associated dysplasias/adenomas (29%) and adenocarcinomas (44%) as compared to flat dysplasias (4%) and adenomas (18%) unassociated with adenocarcinoma (P=0.001). The mean methylation index increased from normal/chronic gastritis (CG) mucosa (0.09) to intestinal metaplasia (IM) (0.16), flat dysplasias (0.40) or polypoid adenomas (0.41) unassociated with carcinoma, dysplasias/adenomas associated with carcinoma (0.44), and adenocarcinomas (0.44). There was no difference in frequencies of high-level CpG island methylation (CIM-H, methylation index > or =0.5) among flat dysplasias (50%) and polypoid adenomas (51%) unassociated with carcinoma, dysplasias/adenomas associated with adenocarcinoma (47%), and adenocarcinoma (47%). CIM-H was present in 15% of IM, but not in normal/CG mucosa. There was a significant correlation between methylation of hMLH1 and high-level of microsatellite instability (MSI-H): methylation of hMLH1 was present in 71% of MSI-H tumors, but only 8% of MSI-low tumors and 13% of microsatellite-stable tumors (P=0.0001). There was no statistical difference between methylation index and APC mutation. Our results indicate that concurrent promoter methylation is an early and frequent event in gastric tumorigenesis, including both MSI-H and microsatellite-stable neoplasms. Methylation of the p16 gene may contribute to the malignant transformation of gastric precursor lesions.
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PMID:Frequent CpG island methylation in precursor lesions and early gastric adenocarcinomas. 1506 7

There are several different approaches available for the palliation of esophago-gastric cancer. The decision on which type of therapy is used should be made individually based on an interdisciplinary consensus.In case of inoperable esophageal carcinoma, it becomes the primary objective of the therapy to maintain oral nutrition. This can be achieved through the insertion of self expanding metal stents as a minimally invasive procedure which results in an immediate elimination of dysphagia. As alternative and/or complementary therapy, radiological techniques (external beam radiation, brachytherapy) can be applied. Other locally endoscopic techniques (laser, APC-beamer) are often used for treating local complications of esophageal and inoperable stomach carcinomas. For these carcinomas palliative chemotherapy with cisplatin has been established as a standard regimen.
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PMID:[Palliative treatment options for esophageal and gastric cancer]. 1524 5

beta-Catenin nuclear translocation is frequently observed in different types of malignancies, including gastric cancer. In gastric cancer, however, the molecular mechanisms leading to accumulation of this protein in the nucleus remain unknown. In this setting, beta-catenin (CTNNB1) mutations have been reported, but studies of mutation frequency have yielded conflicting results. Mutations or silencing of other partners of beta-catenin (i.e., APC and AXIN) are also considered rare genetic events in gastric tumorigenesis. Gene amplification is a common mechanism of activation and/or overexpression of oncogenes in gastric and other cancers. In this study, we investigated whether gene amplification is a possible mechanism of beta-catenin activation in gastric cancer by determining its presence in 49 patients with gastric cancer and two gastric-derived cell lines (KATO III and ST2957). Using fluorescence in situ hybridization, we identified beta-catenin amplification in one of the tumor samples as well as in KATO III cells. beta-Catenin immunostaining revealed nuclear translocation of the protein in both cases. In the KATO III cells, beta-catenin overexpression was confirmed by quantitative real-time PCR and Western blot analyses and beta-catenin gene amplification by Southern blot analysis and multiplex ligation probe amplification. In the KATO III cell line, no correlation was found between beta-catenin nuclear translocation and increased expression of the WNT1 target gene CCND1 (cyclin D1). Our data suggest that gene amplification is a possible mechanism of beta-catenin overexpression in cancer.
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PMID:beta-catenin (CTNNB1) gene amplification: a new mechanism of protein overexpression in cancer. 1560 44


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