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)

Signet-ring cell carcinoma (SRCC) is a unique subtype of adenocarcinoma that is characterized by abundant intracellular mucin accumulation and a crescent-shaped nucleus displaced toward one end of the cell. Identification of an SRCC's primary site is important for better planning of patient management because the treatment and prognosis differs markedly depending on the origin of the SRCC. In the present study, we analyzed the immunohistochemical characteristics of 94 cases of SRCC, including 21 cases of gastric SRCC, 16 of colorectal SRCC, 10 of breast SRCC, and 47 of pulmonary SRCC, with antibodies against Reg IV and claudin-18, which we previously identified as gastric cancer-related genes. We also tested known markers cytokeratin 7, cytokeratin 20, MUC2, MUC5AC, caudal-related homeobox gene 2 (CDX2), thyroid transcription factor-1, mammaglobin, gross cystic disease fluid protein 15, and estrogen receptor. All 21 cases of gastric SRCC and 16 cases of colorectal SRCC were positive for Reg IV, and the remaining SRCCs were negative. Eighteen of 21 (86%) gastric SRCCs and 6 of 16 (38%) colorectal SRCCs were positive for claudin-18, whereas another SRCCs were negative. In conclusion, Reg IV staining and claudin-18 staining can aid in diagnosis of gastrointestinal SRCC.
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PMID:Immunohistochemical staining of Reg IV and claudin-18 is useful in the diagnosis of gastrointestinal signet ring cell carcinoma. 1858 Jun 80

Regenerating gene family members 1 (REG Ialpha) and 4 (REG IV) are overexpressed in a subset of gastric cancers. However, comparative characterization of the expression of these family proteins has remained unclear. Therefore, we aimed to elucidate not only the association between REG protein expression and mucin phenotype but also their significance as a prognostic marker for patients with gastric cancer. The expression of REG Ialpha, REG IV, CDX2, MUC2, and MUC5AC in gastric cancer tissues was examined by immunohistochemistry. The relationship between REG protein expression and clinicopathological parameters or mucin phenotype was then analyzed. REG Ialpha and REG IV expression was positive in 33 (52%) and 31 (49%) of 63 gastric cancers examined, respectively. REG Ialpha expression was significantly related to venous invasion and tumor stage, whereas REG IV expression showed no relationship to clinicopathological features. With regard to mucin phenotype, REG IV expression was significantly correlated with MUC2 and CDX2 expression, suggesting an association with the intestinal mucin phenotype of gastric cancer. On the other hand, REG Ialpha expression had no correlation with MUC2, CDX2, or MUC5AC in gastric cancer tissues. Expression of REG Ialpha but not REG IV was an independent predictor of poor outcome in patients with gastric cancer. In addition, patients with gastric cancer negative for both REG Ialpha and REG IV expression had a significantly better outcome than patients positive for either REG Ialpha or REG IV. Profiling of REG protein expression is useful to for prognostication of patients with gastric cancer.
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PMID:Expression profile of REG family proteins REG Ialpha and REG IV in advanced gastric cancer: comparison with mucin phenotype and prognostic markers. 1932 38

Helicobacter pylori is a major cause of the transdifferentiation into intestinal metaplasia that may develop gastric cancer. However, the molecular pathogenesis of this transdifferentiation is poorly understood. A SRY-related HMG box protein Sox2 is an essential transcription factor of organ development in brain, lung, and stomach. Our aim of this study was to investigate the mechanism responsible for regulation of Sox2 in host Th1-dominant response to H. pylori. Sox2 protein was immunohistochemically expressed in both human oxyntic and pyloric glands with H. pylori infection, but not in intestinal metaplasia. Western immunoblotting of gastric epithelial cell lines showed that IL-4, a Th2-related cytokine, dose dependently enhanced Sox2 expression among H. pylori infection-mediated cytokines. Small changes of Sox2 expression were observed after each treatment with IFN-gamma, IL-1beta, or TNF-alpha. IL-4-mediated Sox2 induction was suppressed by the inhibition of STAT6 activation with STAT6 RNA interference, and electrophoretic mobility shift assay indicated that activation of the Sox2 promoter by IL-4 occurred through the action of STAT6. Furthermore, H. pylori and IFN-gamma inhibited the phosphorylation of STAT6, resulting in the suppression of IL-4-mediated Sox2 expression. Immunohistochemical analyses showed significantly the suppressed STAT6 activity in H. pylori-infected human gastric mucosa. Additionally, downregulation of Sox2 by knockdown experiments led to intestinal phenotype with expressions of Cdx2 and MUC2. These results suggest that H. pylori and IFN-gamma interfere with the differentiation into oxyntic and pyloric glands by the downregulation of Sox2 on IL-4/STAT6 signaling, which may contribute to the transdifferentiation into intestinal metaplasia.
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PMID:Helicobacter pylori induces gastric mucosal intestinal metaplasia through the inhibition of interleukin-4-mediated HMG box protein Sox2 expression. 1952 Jul 37

Cronkhite-Canada syndrome (CCS) is a rare nonhereditary disorder with gastrointestinal polyposis and associated ectodermal changes. This report documents a 59-year-old Japanese man with CCS who underwent a total gastrectomy for gastric tumors. The resected specimen showed a huge gastric adenocarcinoma with numerous polyps throughout the stomach. The cancer was pathologically limited to within the mucosa and its histological structure resembled that of hyperplasia in CCS polyps, which led us to suppose that the carcinoma had arisen from hyperplastic CCS polyps. These results urged us to study the phenotypic expression of mucins, which revealed MUC2(-) and MUC5AC(+) and supported the diagnosis of the tumor as a gastric-type well-differentiate adenocarcinoma. A literature search revealed that 32 gastric carcinomas which developed in patients with CCS were mostly limited to within the submucosa in spite of their huge sizes, and such cancer development in CCS polyposis is therefore not considered to be unusual.
Gastric Cancer 2009
PMID:Cronkhite-Canada syndrome complicated with huge intramucosal gastric cancer. 1956 66

Changes in mucin protein expression and in glycosylation are common features in pre-neoplastic lesions and cancer and are therefore used as cancer-associated markers. De novo expression of intestinal mucin MUC2 and cancer-associated sialyl-Tn antigen are frequently observed in intestinal metaplasia (IM) and gastric cancer. However, despite that these antigens often co-localize, MUC2 has not been demonstrated to be a carrier of sialyl-Tn. By using the in situ proximity ligation assay (in situ PLA), we herein could show that MUC2 is a major carrier of the sialyl-Tn antigen in all IM cases and in most gastric carcinoma cases. The requirement by in situ PLA for the presence of both antigens in close proximity increases the selectivity compared to measurement of co-localization, as determined by immunohistochemistry. Identification of the mucin which is the carrier of a carbohydrate structure offers unique advantages for future development of more accurate diagnostic and prognostic markers.
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PMID:MUC2 mucin is a major carrier of the cancer-associated sialyl-Tn antigen in intestinal metaplasia and gastric carcinomas. 1981 50

Infection of gastric mucosa by Helicobacter pylori induces an inflammatory response with increased levels of proinflammatory cytokines. Among them, tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta and IL-6 induce the activation of signaling pathways that regulate genes expression, such as MUC2 and MUC4 intestinal mucins ectopically detected in gastric tumors. This study evaluated if the predominant inflammatory cell type correlates with MUC2 and MUC4 expression in human intestinal gastric tumors (n=78). In addition, we analyzed the regulatory effects of the associated inflammatory signaling pathways on their expression in gastric cancer cell lines, and in a mouse model with hyperactivated STAT3 signaling pathway. Tumors with predominant lymphoplasmocytic infiltrate (chronic inflammation), presented higher levels of MUC2 and were more differentiated than tumors with predominant polymorphonuclear infiltrate (acute inflammation). These differences can be attributed to specific cytokines, because TNF-alpha and IL-1beta induced MUC2 but no MUC4 expression in gastric cancer cell lines. The two groups of tumors expressed similar levels of MUC4 that correlated with the expression of STAT3 transcription factor, implicated in the activation of genes through the IL-6 pathway. In gastric tissues from gp130(+/+), gp130(Y757F/Y757F) and gp130(Y757F/Y757F) Stat3(-/+) mice, Muc2 was not detected, whereas Muc4 was found in the gastric tumors developed in the gp130(Y757F/Y757F) mice, with hyperactivated STAT3. These data indicate that the signaling pathways associated with the inflammatory response can modulate the expression of MUC2 and MUC4 intestinal mucin genes, in human and mouse gastric tumors.
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PMID:Inflammation modulates the expression of the intestinal mucins MUC2 and MUC4 in gastric tumors. 2006 84

NaB (sodium butyrate) inhibits cell proliferation and induces differentiation in a variety of tumour cells. In this study, we aimed to determine whether NaB induced differentiation and regulated the expression of the mucosal factor MUC2 through the PTEN/PI3K (phosphoinositide 3-kinase) pathway. BGC823 cells treated with NaB for 24-72 h showed marked inhibition of cell proliferation and alteration in cellular morphology. NaB treatment markedly increased the expression of PTEN and MUC2, but it decreased the expression of PI3K. These effects were enhanced by intervention with PI3K inhibitors and were reduced by intervention with PTEN siRNA. Hence, we conclude that NaB increased PTEN expression, promoted the expression of MUC2 and induced the differentiation of gastric cancer cells through the PTEN/PI3K signalling pathway.
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PMID:Sodium butyrate induces differentiation of gastric cancer cells to intestinal cells via the PTEN/phosphoinositide 3-kinase pathway. 2071 12

Tumor cell growth is influenced by the cellular microenvironment including the presence of immune cells and blood vessels. Currently, no transplantable gastric cancer syngeneic animal models exist; therefore, we set out to establish a mouse gastric carcinoma cell line, which was named mouse gastric carcinoma cell line 3I (MGCC3I), from forestomach carcinoma developed in benzo[a]pyrene-treated ICR mice. MGCC3I cells showed epithelial-like morphology, multinuclear giant cell formation, and retained an intestinal phenotype, which are similar to human gastric cancer carcinoma cells. The expression of gastric cancer markers MUC1, MUC2, and MUC5AC, and oncogenes c-myc, c-met, cyclin E1, and cancer stem cell marker CD44 was determined in MGCC3I cells. MGCC3I cells formed poorly differentiated stomach tumors following orthotopic implantation into the stomachs of syngeneic ICR mice. Histone deacetylase inhibitors are recognized as a new class of anticancer drugs. The immunological therapeutic effects of the histone deacetylase inhibitors sodium butyrate and valproic acid were evaluated in this new animal tumor model. Sodium butyrate inhibited MGCC3I stomach tumor formation in animal models. Increased tumor infiltration by CD8 T cells and neutrophils was observed in mice treated with sodium butyrate or valproic acid. Depletion of CD8 T cells significantly attenuated tumor regression mediated by histone deacetylase inhibitors, which is correlated with enhancement of the MHC class I pathway in MGCC3I cells. Taken together, we have successfully established an orthotopic transplantable gastric tumor animal model and demonstrated its usefulness in revealing the role of CD8 T cells in the therapeutic effects of sodium butyrate.
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PMID:Establishment of an orthotopic transplantable gastric cancer animal model for studying the immunological effects of new cancer therapeutic modules. 2073 21

Immunohistochemical studies revealed the dependence of cell regeneration parameters at sites of intestinal metaplasia (IM) in gastric mucosa (GM) on the character of the background events, such as atrophy and erosive-ulcerative defect. Mucin profile was determined in various types of IM. The intestinal type of mucin was found only in type I IM while types II and III were characterized by the mixed gastrointestinal phenotype with expression MUCSAC and MUC2. It was shown that at sites of incomplete IM (types II and III) and atrophic changes of GM cells proliferation activity of epithelium is considerably increased; this increase may be associated with the risk of developing gastric cancer of the intestinal type.
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PMID:[Proliferative and mucin-producing activities in the foci of intestinal metaplasia associated with chronic atrophic gastritis and gastric ulcer]. 2079 97

Apomucins play important biological roles in cell-cell and cell-extracellular matrix interactions, in cell signaling, and in biological properties of cancer cells. Their specific pattern of expression during the different steps of tumor progression toward adenocarcinoma suggests that they play significant roles in tumorigenesis. The family of secreted mucins, gel-forming components of viscoelastic mucus gels protecting the epithelia, includes mucins MUC2 and MUC6. Their principle function is to contribute in mucus formation by forming a tridimensional network via oligomerization domains to protect underlying epithelia against diverse injuries. The current study was investigated the expression of MUC2 and MUC6 in patients with gastric carcinoma. MUC2 and MUC6 expressions were detected immunohistochemically in gastric cancer biopsies using specific monoclonal antibodies. The results showed that in our gastric carcinoma cases, MUC2 expression was detected in 78.6% of cases. MUC2 expression is increased from well differentiated to moderately differentiated to poorly differentiated gastric adenocarcinoma. On the other hand, MUC6 was detected in 32% of cases. The expression of MUC2 is increasing, which is accompanied by an altered expression of MUC6 in gastric cancer. Therefore, it is concluded that the expression pattern of secreted mucins including MUC2 and MUC6 is altered apparently in gastric carcinoma.
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PMID:MUC2 and MUC6 apomucins expression in human gastric neoplasm: an immunohistochemical analysis. 2087 53


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