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)

De-glycosylation of mucins may expose new tumor-associated core protein epitopes. In this study, to attempt to develop useful markers for gastric cancers, we have purified and de-glycosylated gastric mucin and tried to establish monoclonal antibodies (MAbs). A MAb designated A3D4 among established MAbs was shown to react with gastric cancer with high frequency, but not with normal gastric epithelium. Among normal digestive organs, only the colon and gall bladder were positive for MAb A3D4. The incidence of positivity in gastric cancer was 75% for intestinal-type adenocarcinoma (n = 28), 40% for solid-type adenocarcinoma (n = 5) and 33% for signet/scirrhous-type adenocarcinoma (n = 15). Interestingly, adenoma and intestinal metaplasia (IM) with chronic gastritis or peptic ulcer were negative for MAb A3D4, whereas 8 out of 13 cases (62%) of IM with gastric cancer was positive. Western-blot analysis using the lysate from normal colon tissues revealed a high-molecular-weight (> 300-kDa) smear-like band. Immunohistochemical analysis indicated that the reactivity of MAb A3D4 was clearly increased when tissue sections were pre-treated with periodic acid or O-glycanase, while it was decreased by pre-treatment with trypsin or protease V8. There was no reactivity with the synthetic peptide encompassing the tandem-repeat sequence of MUC2 or MUC3. These data suggest that MAb A3D4 detects a novel gastric-cancer-associated mucin antigen whose epitope may be peptide in nature.
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PMID:A novel gastric-cancer-associated mucin antigen defined by a monoclonal antibody A3D4. 939 54

The expression of Bfl-1 gene, a novel Bcl-2 related gene, was determined by Northern blot analysis using a radiolabeled cDNA specific for Bfl-1 gene in 82 surgically resected tissue specimens of 28 gastric cancers, 15 colon cancers, nine breast cancers, eight bone and soft tissue sarcomas, five ovarian cancers, nine colon adenomas and eight gastric adenomas. A high rate of expression was observed in gastric and colon cancer, at 86 and 93%, respectively. In breast cancer, bone and soft tissue sarcoma and ovarian cancer, the expression rate was 33, 25 and 40%, respectively. In stomach cancer, the expression rate of Bfl-1 gene in metastatic lymph nodes was 82%, which was higher than 50% of the primary sites (p < 0.02). The intensity of RNA bands of the gastric cancer specimens was compared according to the stage, demonstrating that there was no difference in the expression levels of Bfl-1 gene between the stages in both primary sites and metastatic lymph nodes. Bfl-1 gene was expressed in three (33%) out of nine adenomas of the colon, while it was not detected in all eight gastric adenomas, We also examined the RNA expression of Bfl-1 gene in 22 human cancer cell lines consisting of five stomach cancer, four squamous cell carcinoma, three lung cancer, three cervical cancer, two colon cancer, two brain cancer, two leukemia and one osteosarcoma cell lines. Bfl-1 gene band was detected in one (5%) cervical cancer cell line, SiHa. The results of cancer tissue specimens indicate that Bfl-1 gene may play an important role in carcinogenesis of human cancers and may be involved in a relatively early phase of the adenoma-carcinoma sequence in colon cancer development. However, the mechanism responsible for the very low rate of expression in established cell lines is not clearly understood and further investigation is necessary to clarify the mechanism involved.
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PMID:Expression of a novel Bcl-2 related gene, Bfl-1, in various human cancers and cancer cell lines. 949 79

Laparoscopy with lesser sac endoscopy (LSE) were used in combination from 1987 to 1992 in 103 patients for differentiation between pancreatic carcinoma and other peripancreatic pathology, staging, and palliation. LSE identified pancreatic carcinoma in 38 patients; pancreatic cystadenocarcinoma in 2 patients; pancreatic cystadenoma in 3 patients; pancreatic adenoma in 1 patient; pancreatic metastases from liver in 2 patients; and pancreatic cysts in 5 patients. False negative diagnosis of pancreatic carcinoma occurred in two cases. Nontumor pancreatic pathology was revealed in 10 patients. Specifically, acute pancreatitis was found in four patients, and chronic pancreatitis was found in six patients. Extrapancreatic cancers were identified in 15 patients: retroperitoneal extraorgan tumors were found in 2 patients; extrahepatic biliary tract cancer in 6 patients; gallbladder cancer in 1 patient; liver cancer in 3 patients; and stomach cancer in 1 patient. In five cases no pathology was found. Overall correct definitive diagnosis was established in 101 patients. Sensitivity of laparoscopy with LSE for pancreatic carcinoma diagnosis proved to be 95 per cent (38 of 40 patients), for pancreatic tumors diagnosis 96.22 per cent (51 of 53 patients); specificity of the method 100 per cent; and accuracy of diagnosis 98 per cent (101 of 103 patients). Thus, the accuracy of the method was as high as the accuracy of combination of all known modalities. Criteria of unresectability were revealed with the combination of LSE and laparoscopy in 75 per cent (30 of 40 cases) of pancreatic carcinoma. Moreover, laparoscopy allowed palliation of pancreatic carcinoma. Laparoscopic cholecystostomy was performed in 10 patients, and laparoscopic cholecystojejunostomy with enteroenterostomy was performed in 6 patients.
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PMID:Lesser sac endoscopy and laparoscopy in pancreatic carcinoma definitive diagnosis, staging and palliation. 973 5

Our aim was to investigate the presence of DNA copy number changes in gastric adenomas and to identify the changes that may play a role in gastric carcinogenesis. DNA copy number changes in 16 patients with gastric adenoma and in 22 tumors from patients with intestinal type gastric carcinomas were studied by using comparative genomic hybridization. DNA copy number changes were found in 44% of the adenoma cases and in 86% of the intestinal type gastric carcinomas. On average, gains were more common than losses (0.9 vs. 0.5 in adenomas and 4.1 vs. 1.8 in carcinomas). In adenomas, the most common gains involved chromosome 8 in 3 cases, and gain of chromosome 7 and 20q was detected in 2 cases. The most frequent losses were observed at 5q (three times). Only adenomas with severe dysplasia showed high-level amplifications that were detected at chromosome 13, 17cen-q22, and 20q12-ter. In gastric cancer, the most common gains were detected at 20q (55%), 17q12-q21 (41%), and 8q (41%), and the most common losses were detected at 18q (41%) and 4q (32%). High-level amplifications were observed at 20q (3 tumors), 17cen-q21 (3 tumors), 2p (1 tumor), and 18q (1 tumor). These findings suggest that the progression of dysplasia is associated with higher levels of DNA copy number increase (e.g., the gains at 17q and 20q), which were typically observed in the intestinal type gastric cancer. Furthermore, the results support the hypothesis that adenoma precedes cancer.
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PMID:Presence of high-level DNA copy number gains in gastric carcinoma and severely dysplastic adenomas but not in moderately dysplastic adenomas. 980 31

Circulating vascular endothelial growth factor (VEGF) was measured in gastric and colorectal cancer patients using an enzyme-linked immunosorbent assay (ELISA). Firstly, serum and plasma samples were collected from 20 normal controls to compare the values of VEGF and to determine which specimen type was most suitable for detecting circulating VEGF. Seventeen of 20 normal controls had plasma VEGF levels under the limit of detection (15 pg/ml) and the levels of the remaining three controls were 21, 22 and 38 pg/ml. In contrast, all serum samples indicated high levels of VEGF (mean 238 pg/ml), ranging from 44 to 450 pg/ml. In a time-course test of two normal controls serum VEGF values increased markedly between 30 and 60 min and remained high, whilst plasma VEGF values were low up to 480 min. Thus, plasma samples are more suitable for the measurement of circulating VEGF. Next, plasma VEGF levels were examined in 44 patients with gastric cancer (8 early, 7 advanced without remote metastasis and 29 metastatic), 13 with colorectal adenoma (2 with focal cancer) and 26 with colorectal carcinoma (8 advanced without metastasis and 18 metastatic) before treatment. An extremely high plasma concentration of VEGF was seen in some cancer patients with metastasis. To discriminate these patients, a cut-off level was determined, considering both the distribution of the sample concentration and the upper limit of 95% confidence area of VEGF in the cancer patients without metastasis. The cut-off value was 108 pg/ml and most cancer patients without metastases had VEGF levels below the cut-off value. In 11 of 29 metastatic gastric cancer patients (38%) and 9 of 18 metastatic colorectal cancer patients (50%), plasma VEGF levels were higher than the cut-off value. Survival was also analysed in the patients with metastasis. It was significantly longer in the patients with low VEGF levels (below the cut-off) than in those with high VEGF levels (logrank test, P = 0.042). 34 patients with metastasis (19 gastric cancer and 15 colorectal cancer) were treated with systemic chemotherapy, and their pretreatment levels of plasma VEGF and conventional tumour markers (CEA and CA19-9) were evaluated in relation to response. The response to chemotherapy was significantly higher in patients with low VEGF levels (< or = 108 pg/ml) than in those with high VEGF levels (P = 0.047). Such a difference was not observed with CEA/CA19-9. In conclusion, plasma VEGF is a useful marker for tumour metastasis and patient survival, and a possible predictive factor for the response of patients with gastrointestinal cancer to chemotherapy.
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PMID:Clinical significance of plasma vascular endothelial growth factor in gastrointestinal cancer. 1007 Mar 8

Gastric adenomas are often detected in the stomach resected for gastric cancer. Previous investigation have revealed that the prevalence of their malignant transformation is generally low, but the frequent coexistence with carcinoma suggests that they may share some common processes with gastric cancer in tumorigenesis. In contrast to the cumulative information about genetic alterations in gastric cancer, inquiries into the genetic changes of adenoma and coexisting carcinoma in the same individual's stomach are still few. We investigated microsatellite instability (MSI) and K-ras point mutations in codons 12 and 13 in 50 lesions of gastric adenomas in 43 cases, and 31 lesions of gastric cancers that coexisted with these adenomas. In gastric adenomas, we found seven lesions (14.0%) to have microsatellite instability (MSI) at one or more loci, and most of them (six cases) had MSI at only one locus and were not associated with alterations in presumable target molecules. MSI was detected more frequently (11/31, 35.5%) and more extensively (five lesions at multiple loci) in accompanying gastric carcinomas. The prevalence of MSI in adenomas was more frequently found in those with synchronous gastric cancer (6/37, 16.2%, vs. 1/13, 7.6%) than without, and gastric adenoma accompanied by gastric cancer with multiple MSI tended to have MSI more frequently than that accompanied by cancer without MSI (4/5, 80%, vs. 1/24, 4.2%; p = 0. 01). In at least some individuals, MSI appears to represent one step in the pathway of gastric tumorigenesis, shared by adenoma and carcinoma. We found K-ras gene alteration in 8 lesions (16.0%) out of 50 gastric flat adenomas and no difference in its prevalence between adenoma with or without cancer. Only one gastric cancer, which had adenoma without K-ras mutation, had K-ras codon 12 mutation. Adenomas with a higher grade of atypia (p < 0.05) more frequently carried K-ras point mutation, which is consistent with the situation in colorectal adenoma. We conclude that MSI, not K-ras mutation, is a shared genetic alteration in adenoma and carcinoma of the individual stomach.
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PMID:Microsatellite instability and K-ras mutations in gastric adenomas, with reference to associated gastric cancers. 1033 99

Our previous studies have demonstrated the significant enzymatic activity of glycogen phosphorylase (GP) in the gastric carcinoma and proliferating cells of particular intestinal metaplasia (IM). This paper reviewed the identification of the GP isoform in the gastrointestinal carcinoma, and the investigation on the role of this molecule in the gastrointestinal carcinogenesis. The only isoform expressed in gastric cancer was brain-type GP (BGP) using polymerase chain reaction (PCR) analysis. The expression of BGP, oncogene products and proliferating cell nuclear antigen in the gastric and colorectal carcinomas, their premalignant lesions, and the normal mucosa were examined using 136 gastric and 96 colorectal surgically resected specimens, and 55 endoscopically resected colorectal adenomas. The BGP visualized by immunohistochemistry was commonly present in intestinal-type gastric (80.6%) and colorectal (83.3%) carcinomas, whereas no BGP expression was seen in the normal human gastric and large intestinal mucosa except in the BGP foci described below. IMs with BGP had close correlation with intestinal-type gastric carcinoma, and some of them coexpressed accumulated p53 protein. The expression of BGP during 'adenoma carcinoma sequence' (ACS) showed excellent correlation with the increased dysplasia and was found prior to p53 expression. Positive staining in overtly normal looking colonic mucosa (BGP foci) was observed mainly around carcinomas without any adenoma component, and frequent p53 mutation (41.2%) was detected in the BGP foci using PCR-single strand conformation polymorphism analysis. It is suggested that BGP is a novel biomarker for carcinogenesis in the intestinal-type gastric carcinoma and in both of the pathways of ACS and the 'de novo' colorectal carcinoma.
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PMID:Carcinogenesis of intestinal-type gastric cancer and colorectal cancer is commonly accompanied by expression of brain (fetal)-type glycogen phosphorylase. 1037 90

Adenomas are established pre-malignant lesions in colorectal carcinogenesis. To date the adenoma-carcinoma sequence for the development of colorectal carcinoma (CRC) has been based largely on molecular data of exophytic, polypoid-type adenomas. Subsequently, a different type of adenoma has been identified: the flat adenoma, so called for its flat, non-exophytic appearance, making it less likely to be detected during conventional endoscopy. However, due to technological advances in endoscopic methods, flat-type adenomas can now frequently be detected and are no longer considered rare colorectal lesions. The phenotype of flat colorectal adenomas differs macroscopically and histologically from exophytic adenomas. Flat colorectal adenomas, as a rule, are tubular structures often revealing high-grade dysplasia, irrespective of the size or villous component. Flat adenomas have also been recognised as pre-cancerous lesions in gastric cancer. Unlike the wealth of clinical and molecular information available for polypoid (exophytic) adenomas, molecular profiles of flat-type lesions have not yet been characterised systematically and the full clinical significance hereto realised. Previous molecular investigation of the K-ras gene in flat colorectal adenomas suggests a distinct pathway in their development. In this study, mutation analysis of the adenomatous polyposis coli (APC) gene using the protein truncation test (PTT) in 20 flat colorectal adenomas in a selected group of 16 patients without hereditary predisposition to colorectal cancer, revealed double truncations of the APC gene in four adenomas. In one of these adenomas a third mutation was detected by DNA sequence analysis.
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PMID:Multiple APC mutations in sporadic flat colorectal adenomas. 1060 69

A 59-year-old Japanese woman presented with two sebaceous neoplasms on the chest wall and on the left cheek. The patient had a history of ascending colon cancer, and her mother had died of gastric cancer. The histopathologic features of both sebaceous neoplasms were vaguely in accordance with those of sebaceous adenoma and sebaceoma. Based on these findings, we diagnosed the patient as having Muir-Torre syndrome. The sebaceous neoplasm on the chest wall exhibited features of a sebaceous adenoma with a unique cystic appearance, namely cystic sebaceous adenoma, which has been reported as a specific marker for Muir-Torre syndrome (MTS). However, histopathologically, both the sebaceous adenoma and sebaceoma had relatively large, vesicular or heterochromous and crowded nuclei with some pleomorphism and distinct nucleoli associated with some mitotic figures, casting doubt on their benignancy. We show that some or most benign sebaceous neoplasms in MTS might have a high potential for malignant transformation or may be well-differentiated sebaceous carcinomas with low-grade malignancy, mimicking sebaceous adenoma/sebaceoma. This results in difficulties in classification regarding sebaceous neoplasms in MTS.
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PMID:Sebaceous neoplasms in Muir-Torre syndrome. 1077 Apr 37

Hereditary nonpolyposis colorectal cancer (HNPCC) is caused by a germline mutation in one of several DNA repair genes, which in the tumors is reflected as microsatellite instability (MSI). MSI+ tumors have been found to carry somatic frameshift mutations in mononucleotide repeats within the coding regions of several genes involved in growth control, apoptosis, and DNA repair, e.g., TGFBRII, BAX, IGFIIR, TCF4, MSH3, and MSH6. We have studied the occurrence of somatic frameshift alterations in these mononucleotide repeat-containing genes in 24 tumors (15 colorectal cancers, 1 colon adenoma, 4 endometrial cancers, 1 ovarian cancer, 1 gastric cancer, 1 urothelial cancer, and 1 duodenal cancer) from 14 individuals in an HNPCC family with germline hMSH2 mutation. Such somatic frameshift mutations occurred at a variable frequency; the long mononucleotide repeats that characterize intronic MSI markers were mutated in the majority of tumors, 13 of the tumors displayed alterations in the (A)(10) tract of TGFBII, eight tumors (all of gastrointestinal origin) had alterations in the (A)(9) repeat of TCF4, and one to five tumors had somatic frameshift alterations in the shorter mononucleotide repeats of IGFIIR, BAX, MSH3, and MSH6. Thus, longer mononucleotide repeats were more frequently affected by somatic frameshift mutations. The pattern of alterations varied between the tumors from different family members as well as between different tumors from the same individual. To what extent this variable pattern depends on the widespread mismatch repair deficiency induced by the underlying MSH2 mutation, or represents alternative ways whereby the tumors can achieve a tumorigenic phenotype, is unknown. We suggest, however, that the accumulation of somatic frameshifts, rather than the specific loci in which these occur, drives the development of the tumorigenic phenotype in HNPCC.
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PMID:Somatic frameshift alterations in mononucleotide repeat-containing genes in different tumor types from an HNPCC family with germline MSH2 mutation. 1091 91


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