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

Proteolytic degradation of extracellular matrix is a critical step in tumour invasion and metastasis. To examine the role of trypsin in tumour dissemination, we cloned two variants (S4 and R3 cells) from STKM-1, a trypsinogen 1-producing diffuse gastric cancer cell line. Western blot analysis with antitrypsin antibody showed that 26 and 24 kDa proteins were highly detected in S4 conditioned medium (CM) in comparison to R3 CM. In addition to the 26 and 24 kDa proteins, 25 and 23 kDa bands, which correspond to enterokinase-activated trypsin, were found only in S4 CM. When the CMs of the two clones were treated with enterokinase, the 25 and 23 kDa trypsin activities in S4 CM were effectively increased as compared with R3 CM. When the two clones were inoculated intraperitoneally (i.p.) into nude mice, S4 cells strongly invaded the liver, pancreas and peritoneum and killed the hosts more rapidly than R3 cells: the 50% survival time was 50 days for S4 and 82 days for R3 cells. These results suggest that trypsin production is associated with the invasive growth of STKM-1 gastric cancer cells.
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PMID:Production of trypsins by human gastric cancer cells correlates with their malignant phenotype. 984 64

It has previously been reported that the trypsinogen gene is expressed in various human cancers. To investigate the possible role of trypsin in tumor malignancy, trypsinogen-1 cDNA was introduced into the human gastric carcinoma cell line MKN-1. The overexpression of trypsinogen-1 in MKN-1 cells stimulated cellular growth and adhesion to fibronectin and vitronectin when the trypsinogen activator enterokinase was added into the culture. Enterokinase treatment of the conditioned medium of the MKN-1 transfectants partially converted the proforms of gelatinases B and A to their apparent active forms. When the MKN-1 transfectants expressing trypsinogen-1 were intraperitoneally transplanted into nude mice, the mice frequently produced tumors in the colon, spleen and liver. However, the mice implanted with control MKN-1 cells produced no tumors. These results strongly suggest that tumor-derived trypsin contributes to the disseminated growth of some types of cancer cells including gastric cancer.
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PMID:Stimulation of cellular growth and adhesion to fibronectin and vitronectin in culture and tumorigenicity in nude mice by overexpression of trypsinogen in human gastric cancer cells. 993 8

In Helicobacter pylori-associated gastric mucosal injury, interleukin (IL) -8, a potent leukocyte chemoattractant, is produced by epithelial cells infected by H. pylori and directs neutrophils to the gastric mucosa. According to previous studies, the IL-8 production requires direct contact between the bacteria and epithelial cells. The aims of the present study were to determine whether an H. pylori water extract (HPE) induces IL-8 production by gastric epithelial cells and to characterize IL-8-inducing substances in HPE. Extracts were prepared from a standard strain and from strains obtained from patients with gastric ulcers. After addition of HPE to MKN 45 cells, a gastric cancer cell line, IL-8 in supernatants and IL-8 mRNA were measured by immunoassay and reverse transcription-polymerase chain reaction, respectively. For characterization, active fractions obtained by gel filtration of standard-strain HPE were treated by heating or trypsinization. To study the signal pathway leading to IL-8 production, inhibitors for protein kinase A (PKA), protein kinase C (PKC), or protein tyrosine kinase (PTK) were incubated with MKN45 cells before HPE stimulation. HPE from the standard strain and one of these clinical strains induced IL-8 production. Lipopolysaccharide or cagA in the strains showed no correlation with IL-8 concentration. Standard-strain HPE induced IL-8 mRNA expression in MKN 45 cells. Gel filtration localized activity to a low-molecular-weight fraction of about 7 kDa, which was resistant to heat and trypsin digestion. PKC inhibitors significantly blocked HPE-induced IL-8 production by MKN 45 cells; however, the PKA inhibitor or PTK inhibitors showed a partial inhibitory effect. HPE contains a nonprotein substance of low molecular weight that is responsible for IL-8 induction in gastric epithelial cells. This induction is mainly dependent on the activation of PKC but partially also dependent on PKA or PTK.
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PMID:Helicobacter pylori water extract induces interleukin-8 production by gastric epithelial cells. 1006 6

It was recently found that overexpression of the trypsin gene in tumor cells stimulates their growth in culture and in nude mice. In the present study, expression of trypsin in various human cancer cell lines and tissues was studied by gelatin zymography and immunoblotting before and after enterokinase treatment and by immunohistochemistry. The analyses showed that many stomach, colon, and breast cancer cell lines secreted trypsinogens-1 and/or -2, as well as an unidentified serine proteinase of about 70 kDa, into culture medium. Lung cancer cell lines secreted 18- and 19-kDa unidentified trypsin-like proteins. Stomach cancer cell lines frequently secreted active trypsin, suggesting that they produced an endogenous activator of trypsinogen, most likely enterokinase. Active trypsin formed a complex with a soluble form of Alzheimer amyloid precursor protein (sAPP), a Kunitz-type trypsin inhibitor, which was secreted by all cell lines tested. This indicated that sAPP is a primary inhibitor of secreted trypsin. Immunohistochemical analysis showed that trypsin(ogen) was frequently expressed at high levels in stomach and colon cancers, but scarcely in breast cancers. In the stomach cancers, the trypsin immunoreactivity was higher in the malignant, non-cohesive type than in the cohesive type. These results support the hypothesis that tumor-derived trypsin is involved in the malignant growth of tumor cells, especially stomach cancer cells.
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PMID:Expression of trypsin in human cancer cell lines and cancer tissues and its tight binding to soluble form of Alzheimer amyloid precursor protein in culture. 1034 9

Linitis plastica, or Borrmann 4 gastric cancer, shows very poor prognosis, and the reason has not been understood. In the present study, we examined serum levels of trypsin(ogen) in 44 gastric cancer patients, including 17 early gastric cancer, 18 non-Borrmann 4 advanced gastric cancer, and 9 Borrmann 4 gastric cancer, by using the RIA gnost Trypsin kit (Hoechst Japan, Tokyo, Japan), which was expected to detect trypsin-1, trypsin-2, trypsinogen-1, and trypsinogen-2 in sera. The trypsin(ogen) concentration was much higher in the patients with linitis plastica than in the other gross types of gastric cancer. Hypertrypsinemia was identified in approximately 60% of advanced gastric cancer cases. Lymph node involvement, liver metastasis, or poorly differentiated adenocarcinoma is an important factor of hypertrypsinemia. The serum trypsin(ogen) level in linitis plastica patients was 3484.4 +/- 2319.7 ng/ml (mean +/- SD), which was significantly higher not only than that of the early gastric cancer (384.1 +/- 92.1) but also the stage IV gastric cancer patients (578 +/- 440.4), excluding those with linitis plastica. The elevated serum trypsinogen level in linitis plastica patients may be related to the malignant behavior of this type of cancer cell. Serum trypsin(ogen) of linitis plastica shows significantly higher concentrations than do the other types of advanced gastric cancer. Therefore, serum concentration of trypsin(ogen) might be a good marker of gastric cancer of linitis plastica.
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PMID:Marked increase of trypsin(ogen) in serum of linitis plastica (gastric cancer, borrmann 4) patients. 1077 67

BACKGROUND: In Japan, much attention has recently been paid to super-extended paraaortic lymphadenectomy (PAL) for the treatment of advanced gastric cancer. However, it has been reported that PAL is associated with increased morbidity and mortality, as compared to conventional extended lymphadenectomy (D2 or D3). Therefore, an analysis of the effects of PAL on perioperative changes in the biological responses of patients essential for determining the potential utility of this procedure.METHODS: The current non-randomized prospective study included evaluations of perioperative changes in parameters of surgical stress (series I; serum levels of antidiuretic hormone, interleukin-6, trypsin, and phospholipase A(2)) and immunocompetence (series II; phytohemagglutinin- and concanavalin A-induced blastogenesis, activity of natural killer cells and the ratio of CD4 cells to CD8 cells) in patients with advanced gastric cancer (T3 or T4), comparing groups treated with D3 plus PAL ( n = 12) and D3 ( n = 13), and a control group with early gastric cancer ( n = 16) treated with D1 lymphadenectomy (perigastric N1 nodes) between April 1995 and April 1997.RESULTS: The duration of surgery and the amount of blood lost were longer and greater in the D3 plus PAL group than in the D3 and D1 groups. D3 plus PAL and D3 were associated with significant postoperative increases in parameters of surgical stress, as well as with significant postoperative immunosuppression, compared to results with D1. However, there were no significant differences in the respective parameters between the D3 plus PAL and D3 groups.CONCLUSIONS: Our results indicate that there are no essential differences in patients' biological responses between D3 plus PAL and D3 lymphadenectomy. It appears that PAL-associated morbidity can be minimized by very careful manipulation during the dissection of paraaortic lymph nodes.
Gastric Cancer 1998 Dec
PMID:Effects of super-extended paraaortic lymphadenectomy (PAL) on biological responses in totally gastrectomized patients with T3 or T4 gastric cancer. 1195 44

A case of gastric carcinoma resembling pancreatic mixed acinar-endocrine carcinoma of 77-year-old female is presented. This type of gastric tumor has not been previously reported. The endoscopic mucosal resection specimen of the fundus contained a 1.2 x 0.9 x 0.3 cm, well-circumscribed, tan, soft nodular tumor with protruded configuration with a central recess. Histologically, the tumor was confined to the mucosa and submucosa and was characterized by three growth patterns; acinar, solid, and glandular. The growth patterns were intermingled. The tumor cells in the acinar component had round nuclei with prominent nucleoli and diastase-resistant, periodic acid-Schiff-positive, eosinophilic cytoplasm. Immunohistochemically, the tumor cells were positive for CAM5.2, cytokeratin (CK) 7, CK 20, trypsin, lipase, alpha-1-antitrypsin, and alpha-1-antichymotrypsin. The tumor cells in the solid component were positive for Grimelius stain and chromogranin A. The findings indicated that the tumor showed acinar and endocrine differentiation. There was no heterotopic pancreas tissue in the specimen. The patient was well without tumor at the 7-month follow-up. It is important to know the existence of this type of gastric cancer and to not confuse it with a metastatic lesion of the pancreatic origin.
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PMID:Gastric carcinoma resembling pancreatic mixed acinar-endocrine carcinoma. 1209 86

Two-dimensional gel electrophoresis (2-DE) maps for human stomach tissue proteins have been prepared by displaying the protein components of the tissue by 2-DE and identifying them using mass spectrometry. This will enable us to present an overview of the proteins expressed in human stomach tissues and lays the basis for subsequent comparative proteome analysis studies with gastric diseases such as gastric cancer. In this study, 2-DE maps of soluble fraction proteins were prepared on two gel images with partially overlapping pH ranges of 4-7 and 6-9. On the gels covering pH 4-7 and pH 6-9, about 900 and 600 protein spots were detected by silver staining, respectively. For protein identification, proteins spots on micropreparative gels stained with colloidal Coomassie Brilliant Blue G-250 were excised, digested in-gel with trypsin, and analyzed by peptide mass fingerprinting with delayed extraction-matrix assisted laser desorption/ionization-mass spectrometry (DE-MALDI-MS). In all, 243 protein spots (168 spots in acidic map and 75 spots in basic map) corresponding to 136 different proteins were identified. Besides these principal maps, overview maps (displayed on pH 3-10 gels) for total homogenate and soluble fraction, are also presented with some identifications mapped on them. Based on the 2-DE maps presented in this study, a 2-DE database for human stomach tissue proteome has been constructed and is available at http://proteome.gsnu.ac.kr/DB/2DPAGE/Stomach/. The 2-DE maps and the database resulting from this study will serve important resources for subsequent proteomic studies for analyzing the normal protein variability in healthy tissues and specific protein variations in diseased tissues.
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PMID:Proteome analysis of human stomach tissue: separation of soluble proteins by two-dimensional polyacrylamide gel electrophoresis and identification by mass spectrometry. 1221 Feb 10

There is increasing interest in the use of rare earth elements in medicine. However, the biological mechanism of action of this metal ion remains unclear. In the present study, changes in protein synthesis induced by lanthanum in BGC-823 human gastric cancer cells were investigated. The proteins were separated using two-dimensional polyacrylamide gel electrophoresis and four proteins were significantly affected by lanthanum treatment when compared to an untreated control. Among them, one was down-regulated and three were up-regulated. Of these, three were successfully identified as RHOJ, CSP6 and MPI2 with peptide mass fingerprinting using matrix-assisted laser desorption/ionization time of flight mass spectrometer (MALDI-TOF-MS) after in-gel trypsin digestion. Among them, RHOJ was down-regulated and CSP6 and MPI2 were up-regulated. The three proteins are involved in various cellular functions, which are correlated with the regulation of cell morphology, gene transcription and cell cycle, respectively. It is suggested that the possible involvement of rare earth elements in the growth arrest of tumor cells is significantly associated with the differential protein expression induced by rare earth ions.
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PMID:Proteomic detection of changes in protein synthesis induced by lanthanum in BGC-823 human gastric cancer cells. 1586 14


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