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 M(r) 78,000 glucose-regulated protein (GRP78) can be induced by physiological stresses such as glucose deprivation and hypoxia. In solid tumors, hypoxia can promote malignant progression and confer resistance to irradiation and chemotherapy by altering gene expression. Here, we investigated the molecular mechanisms and signaling pathway involved in the late and prolonged induction of the GRP78 gene by hypoxia in a human gastric cancer cell line, MKN28. Nuclear run-on assays and mRNA stability measurements revealed that transcriptional activation, not stabilization of mRNA, contributed to the dramatic induction of GRP78 gene under hypoxia. Induction of GRP78 by chronic hypoxia was completely abolished by pretreatment with PD98059 [a specific inhibitor of mitogen-activated protein/extracellular signal-regulated kinase (ERK) kinase (MEK1)] or by overexpression of a dominant-negative MEK1 mutant, demonstrating a direct involvement of ERK in the induction of transcription at the GRP78 promoter under these conditions. Furthermore, hypoxia increased the transcriptional activity of a 12-O-tetradecanoylphorbol-13-acetate response element-like motif on the GRP78 promoter and increased the abundance and DNA binding activity of AP-1 complex composed of c-Jun and c-Fos. A selective protein kinase C (PKC) inhibitor, GF109203X, inhibited the induction of GRP78 gene expression as well as the activities of both ERK and Raf-1. Among six PKC isoforms expressed in MKN28 cells, PKC-epsilon expression level and kinase activity were increased by hypoxia. Transfection of MKN28 cells with a dominant-negative PKC-epsilon blocked the induction of GRP78 through ERK by hypoxia, indicating that PKC-epsilon directly participated in GRP78 induction under hypoxia. Taken together, this study shows that a PKC-epsilon-Raf-1-MEK-ERK-AP1 signaling cascade acts on a 12-O-tetradecanoylphorbol-13-acetate response element-like element to mediate hypoxia-induced GRP78 expression in human gastric cancer cells. We also confirmed in vivo the overexpression of GRP78 in surgical specimens of human primary gastric tumors.
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PMID:Induction of glucose-regulated protein 78 by chronic hypoxia in human gastric tumor cells through a protein kinase C-epsilon/ERK/AP-1 signaling cascade. 1171 66

A 61-year-old female with a past history of gastric cancer presented with altered mental status, a few seizures, and low-grade fever. Lumbar puncture revealed elevated cerebrospinal fluid (CSF) pressure, lymphocytic pleocytosis, elevated protein level, remarkably decreased glucose level, and presence of cryptococcal antigen. Cryptococcus neoformans was identified by India ink staining and culture of CSF. The patient was given antifungal agents intravenously and intrathecally. CSF findings improved and C. neoformans could not be detected in CSF one month after the onset. Cerebral sulcal hyperintensity was identified in the bilateral frontal and parietal lobes on fluid-attenuated inversion recovery (FLAIR) magnetic resonance (MR) imaging one month after the onset, but no leptomeningeal enhancement was detected in the affected sulci on T1-weighted MR imaging. The sulcal hyperintensity on FLAIR imaging developed in the bilateral temporal and occipital lobes 2 months after the onset. CSF findings obtained by lumbar puncture were within the normal range except for pressure. However, neurological deterioration and reconfirmation of C. neoformans in CSF indicated recurrent cryptococcal inflammation. The sulcal hyperintensity on FLAIR imaging may indicate a high CSF protein concentration in the subarachnoid space. Such cerebral sulcal hyperintensity is an unusual MR imaging finding of cryptococcal meningoencephalitis, and may be an early sign of procrastinating process or recurrent inflammation even if the findings of CSF obtained by lumbar puncture are normal.
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PMID:Cryptococcal meningoencephalitis presenting with an unusual magnetic resonance imaging appearance--case report. 1176 Mar 90

The classical risk factors for acute myocardial infarction (AMI) fail to explain all the epidemiological variations of the disease. Among the risk factors recently reported, several infectious agents appear to increase the risk of AMI. Helicobacter pylori (H. pylori) infection, a bacterium involved in duodenal and gastric ulcer, gastric cancer and MALT-lymphoma, seems to be strongly associated with AMI. More virulent (anti-CagA positive) strains of the bacterium are almost exclusively the causative agents of such diseases. To determine the prevalence of H. pylori infection and of virulent strains, a case-control study was conducted in a group of male patients with AMI. A group of patients consecutively admitted to the Emergency Care Unit served as controls. We studied 223 consecutive male patients, mean age 60.2 (range 40-79) years, admitted for AMI to the Coronary Care Units at Hospitals in two towns of Northern Italy, 223 age matched male patients (mean age 61.8, range 40-79 years) admitted to the Emergency Care Unit, served as control. H. pylori seroprevalence was assessed by presence of antibodies (IgG) against H. pylori and anti-CagA in circulation. Among the patients we investigated the presence of hypertension, levels of cholesterol and glucose in serum, fibrinogen in plasma and smoking habits. H. pylori infection was present in 189/223 (84.7%) of the patients and in 138/223 (61.8%) of the control population (p < 0.0001 OR 3.42 [IC 95% 2.12-5.54]). The anti-CagA antibodies were detected in 33.8% of infected patients with AMI (64/189) versus 26.8% in the control subjects (37/138) (p:0.17, OR 1.40 [IC 95% 0.84-2.33]). Classical risk factors for AMI did not differ among patients with and without H. pylori infection. Patients admitted to the Coronary Care Unit for acute myocardial infarction had a notably higher prevalence of anti-H. pylori not restricted to virulent strains, when compared to a population of patients referred to the Emergency Care Unit. The classical risk factors for coronary disease were present in the patients with AMI irrespective of H. pylori status.
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PMID:Infection by Helicobacter pylori and acute myocardial infarction. Do cytotoxic strains make a difference? 1217 73

Gastric cancer is a very serious disease and is naturally resistant to many anticancer drugs. To reduce the mortality and improve the effectiveness of therapy, many studies have tried to find key biomarkers. Proteomic technologies are providing the tools needed to discover and identify disease-associating biomarkers. The proteomic study of gastric cancer establishes any specific events that lead to cancer, and it provides a direct way to define the true function of genes. Using two dimensional (2-D) electrophoresis of the stomach cancer tissue, we have gained about 1,500 spots in each gel, and 140 protein spots also were identified. Among the identified proteins, there were seven over-expressed proteins in stomach cancer tissue: NSP3, transgelin, prohibitin, heat shock protein (hsp) 27 and variant, protein disulfide isomerase A3, unnamed protein product and glucose regulated protein. There were also seven under-expressed proteins in stomach cancer: Apolipoprotein A-1, p20, nucleoside diphosphate isomerase A, alpha 1 antitrypsin, desmin, serum albumin and serotransferrin.
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PMID:The proteomics approach to find biomarkers in gastric cancer. 1292 26

Esophageal cancer is one of the most lethal of all neoplasms. During the last two decades, there have been significant changes in the epidemiology and treatment of esophageal cancer. The incidence of adenocarcinoma is increasing whereas that of squamous cancer is decreasing. Surgery, the mainstay of treatment of esophageal cancer, has been used with neoadjuvant chemoradiotherapy to improve prognosis in patients with localized disease. Accurate staging is essential for selection of the best mode of therapy and to predict prognosis. In addition, with widespread use of neoadjuvant therapy, accurate assessment of response to therapy has become very important because responders have better a prognosis than nonresponders. Anatomical imaging methods, such as computed tomography and endoscopic ultrasonography, that are commonly used to evaluate esophageal cancer have shortcomings in demonstrating the true extent of disease and in assessing or predicting response to therapy. Positron emission tomography (PET) with 2-[(18)F]fluoro-2-deoxy-d-glucose (FDG) has been shown to be a useful adjunct to anatomical imaging methods. For initial staging of esophageal cancer, the combination of PET and endoscopic ultrasonography with fine-needle aspiration biopsy has been suggested to be the most effective strategy. For restaging and monitoring response to therapy, FDG-PET has been shown to be superior to conventional imaging. The incidence of gastric cancer is decreasing worldwide, but it is also a highly lethal cancer. Similar to esophageal cancer, noninvasive staging of this cancer is unsatisfactory. Approximately one-third of the patients thought to have limited disease and to be candidates for surgery by conventional staging methods, are found to have advanced disease at surgery. Only a few published studies have evaluated gastric cancer with FDG-PET. These studies suggest that FDG-PET may be useful in evaluating gastric cancers of intestinal type and nonmucinous tumors.
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PMID:Neoplasms of the esophagus and stomach. 1520 1

We report herein the efficacy and feasibility of weekly administration of paclitaxel for advanced/recurrent gastric cancer retrospectively. Eleven patients with advanced or recurrent gastric cancer who had received prior chemotherapy were treated with this regimen. Seventy mg of paclitaxel per m2 dissolved in 250 ml 5% glucose was administered by 1-hour intravenous infusion once a week for 3 weeks followed by 1 week rest. To avoid hypersensitivity reactions, the following short premedication was given to all the patients 1 hour before paclitaxel treatment: Dexamethasone 20 mg intravenously (i.v.), diphenhydramine 50 mg i.v., and ranitidine 50 mg i.v. Treatment cycle was 1 to 23 with an average cycle of 5.4. The response rate was 33% (2/6 with measurable lesions), the median time to progression was 104 days, and the median survival time was 160 days. Grade 3 neutropenia occurred in 27.2% of the patients. Weekly paclitaxel may be a promising regimen as a second-line chemotherapy for advanced/recurrent gastric cancer. However, special attention needs to be paid to the neutropenic adverse effect in gastric cancer patients with poor performance status than 2 (greater).
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PMID:[Usefulness of weekly administration of paclitaxel for advanced or recurrent gastric cancer]. 1522 4

The three major aims of imaging in esophageal and gastric cancer are to distinguish between locoregional and systemic disease (M stage), to determine local tumor extension (T and N stages), and to assess response to chemotherapy or chemoradiotherapy. Depending on the applied standard of reference, the sensitivity of computed tomography (CT) for detection of distant metastases ranges between less than 50% to greater than 90%. In esophageal cancer, positron emission tomography with the glucose analog fluorodeoxyglucose (FDG-PET) has been shown to detect metastatic disease in approximately 20% of the patients who were considered to have only locoregional disease with CT. In clinical studies, endoscopic ultrasound (EUS) has been shown to differentiate between tumor stages T1/T2 and stages T3/T4 with an accuracy of more than 90%. Accuracy of EUS for differentiating individual tumor stages in routine clinical use has been reported to be markedly lower. Assessment of tumor response by FDG-PET has been shown to correlate with histopathologic tumor regression and patient survival. Furthermore, quantitative measurements of tumor FDG uptake may predict histopathologic tumor response and patient outcome as early as 2 weeks after initiation of preoperative chemotherapy.
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PMID:Imaging of esophageal and gastric cancer. 1529 44

SLC5A8 is a candidate tumour suppressor gene that is silenced in colon cancer, gastric cancer and possibly other cancers in humans. This gene codes for a transporter belonging to the Na(+)/glucose co-transporter gene family (SLC5). The cancer-associated silencing of the gene involves hypermethylation of CpG islands present in exon 1 of the gene. SLC5A8 is expressed in colon, ileum, kidney and thyroid gland. The protein coded by the gene mediates the Na(+)-coupled and electrogenic transport of a variety of monocarboxylates, including short-chain fatty acids, lactate and nicotinate. It may also transport iodide. The normal physiological function of this transporter in the intestinal tract and kidney is likely to facilitate the active absorption of short-chain fatty acids, lactate and nicotinate. One of the short-chain fatty acids that serves as a substrate for SLC5A8 is butyrate. This fatty acid is an inhibitor of histone deacetylases and is known to induce apoptosis in a variety of tumours including colonic tumour. Since butyrate is produced in the colonic lumen at high concentrations by bacterial fermentation of dietary fibre, we speculate that the ability of SLC5A8 to mediate the entry of this short-chain fatty acid into colonic epithelial cells underlies the potential tumour suppressor function of this transporter.
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PMID:Biological functions of SLC5A8, a candidate tumour suppressor. 1566 16

The glycemic effects of diets high in refined grains and starchy foods might increase stomach cancer risk by affecting circulating glucose, insulin and insulin-like growth factor-I levels. No prospective data on the role of high glycemic load and glycemic index diets on stomach cancer risk have been reported. We therefore prospectively investigated dietary glycemic load, overall glycemic index and carbohydrate intake in relation to the incidence of stomach cancer among 61,433 women in the population-based Swedish Mammography Cohort. Diet was assessed at baseline (1987-1990) and again in 1997. During 903,586 person-years of follow-up, a total of 156 incident cases of stomach cancer were ascertained. We observed no material associations of dietary glycemic load, overall glycemic index and total carbohydrate intake with the risk of stomach cancer. The multivariate hazard ratios for the highest versus the lowest quintile were 0.76 (95% CI = 0.46-1.25) for glycemic load, 0.77 (95% CI = 0.46-1.30) for overall glycemic index and 0.85 (95% CI = 0.50-1.43) for carbohydrate intake. The associations did not vary according to body mass index. Lack of information on Helicobacter pylori infection status did not allow stratification by this potential effect modifier. Findings from this population-based prospective cohort of middle-aged and elderly women did not provide evidence of a positive association between glycemic load, glycemic index and carbohydrate intake with risk of stomach cancer.
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PMID:Glycemic load, glycemic index and carbohydrate intake in relation to risk of stomach cancer: a prospective study. 1639 7

Stomach cancer is one of the leading causes of cancer mortality worldwide. Complete resection of a gastric tumor and adjacent lymph nodes represents the only potentially curative intervention. Computed tomography (CT) has remained the modality of choice for the preoperative staging of gastric cancer and for follow-up. A recently developed advanced CT technique that makes use of thin sections, optimal contrast material enhancement, and multiplanar reformation allows more accurate staging. However, CT may be limited in the identification of nonenlarged lymph node metastasis, peritoneal dissemination, and small hematogenous metastasis. Positron emission tomography (PET) with 2-[fluorine-18]fluoro-2-deoxy-d-glucose (FDG) has been recognized as a useful diagnostic technique in clinical oncology. FDG PET allows scanning of a larger volume than is possible with CT. Although FDG PET is not an appropriate first-line diagnostic procedure in the detection of stomach cancer and is not helpful in tumor staging, it may play a valuable role in the detection of distant metastases, such as those of the liver, lungs, adrenal glands, ovaries, and skeleton. FDG PET may also be helpful in the follow-up of patients undergoing chemotherapy, as it allows the identification of early response to treatment. Further studies are needed to determine the efficacy of FDG PET in the detection of local nodal metastases and peritoneal dissemination. Nevertheless, the combined use of CT and PET can be helpful in the preoperative staging of stomach cancer and in the therapeutic monitoring of affected patients.
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PMID:CT and PET in stomach cancer: preoperative staging and monitoring of response to therapy. 1641 49


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