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 EGF stimulation system for growth regulation is implicated in normal and neoplastic cell proliferation. The role of EGF, the EGF receptor, and c-erbB-2 in human gastric cancer is reviewed on the basis of several reports, which have been mainly oriented toward their clinical significance. EGF has been shown immunohistochemically to be present in 26% of gastric cancers (n = 395). The presence of EGF in gastric cancer is correlated with the degree of gastric wall invasion and lymph node metastasis. The 5-year survival of patients with EGF-positive tumors is worse than that of patients with EGF-negative tumors. The presence of EGF in human gastric cancer may therefore represent a higher malignant potential. Fifteen percent of gastric cancers (n = 352) were also shown to be positive for both EGF and the EGF receptor immunohistochemically, and the simultaneous occurrence of EGF and the EGF receptor suggests that these tumors grow in an autocrine fashion. Tumors exhibiting EGF and the EGF receptor simultaneously show a greater degree of local invasion and lymph node metastasis. Increased expression of EGF receptor protein in gastric cancer appears to be related to biologic aggressiveness, although gene amplification has occurred only to a small extent. Twelve percent of gastric cancers (n = 486) were found to be positive for c-erbB-2. This type of tumor has a frequent metastasis, and patients with c-erbB-2-positive cancer have a poorer prognosis than those with c-erbB-2-negative tumors. Selective blockade of the EGF receptor and c-erbB-2 from their ligands with monoclonal antibodies (MoAbs) inhibits the growth of human gastric cancer xenografts. These MoAbs may therefore be effective antitumor agents against gastric cancer showing overexpression of EGF receptors or c-erbB-2.
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PMID:Clinical significance of epidermal growth factor (EGF), EGF receptor, and c-erbB-2 in human gastric cancer. 788 68

The new monoclonal antibodies (MoAbs) E401, E811, E907 and E919 were prepared and characterized. These recognized an extracellular domain (amino acids No. 292-370) on the human c-erbB-2 gene product. Utilizing MoAb E811 and MoAb E919, a double determinant immunoassay (DDIA) was established to detect the soluble and the shed forms of the c-erbB-2 molecule. The levels of circulating erbB-2 antigen in the sera of patients with benign diseases and healthy controls were very low. The incidence of positivity for shed c-erbB-2 antigen in gastric cancer, colonic cancer, gall-bladder cancer, pancreatic cancer and other cancers were 7.4%, 4.2%, 0%, 6.7% and 0%, respectively. Four of 54 patients with gastric carcinoma showed high levels of serum c-erbB-2 antigen. They belonged to clinical stage IV and their histological types were all well differentiated adenocarcinomas (two papillary and two tubular adenocarcinomas). Furthermore, the incidence of positive staining in gastric cancer was 34.6%; higher than that for shedding erbB-2 antigen. Most of the cases which showed erbB-2 expression on cells were well-differentiated adenocarcinomas. Meanwhile, the distribution of erbB-2 antigen was limited in normal tissues. The results suggest that the expression of erbB-2 antigen is largely restricted to adenocarcinoma cells. It may not shed easily from these cells, and therefore it may be a very useful target molecule for passive immunotherapy.
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PMID:Significance of erbB-2 gene product as a target molecule for cancer therapy. 791 Jul 4

The expression of p185erbB2 and p21ras was determined immunohistochemically in normal mucosa, intestinal metaplasia, dysplasia and in intestinal and diffuse type carcinoma of the stomach. The positive rates of p185erbB2 and p21ras in intestinal type were significantly higher than those of diffuse-type carcinoma. The results indicate that there are differences not only in clinical and biologic features, but also in molecular abnormalities between the two types of stomach cancer. Positive staining of cell membrane for p185erbB2 was observed specifically in intestinal type cancer, but not in the other lesions. Positive expression of p185erbB2 on the cell membrane appears to be a useful marker in identification of malignant change of gastric mucosa, as well as a late event of gastrocarcinogenesis. The results of in situ hybridization analysis in cancer tissues were consistent with those obtained by immunohistochemistry and demonstrated amplification of erbB2 gene at the mRNA level. No significant difference of p21ras expression was found among intestinal metaplasia, dysplasia, and intestinal type carcinoma; therefore, it might not be a specific marker of malignancy in gastric mucosa. Expression of p21ras may be an early event in the development of lesions predisposing to carcinoma.
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PMID:Expression of p185erbB2 and p21ras in carcinoma, dysplasia, and intestinal metaplasia of the stomach: an immunohistochemical and in situ hybridization study. 791 79

We recently established epidermal growth factor (EGF) receptor-hyperproducing human gastric cancer xenografts in nude mice. The present study was designed to examine whether the growth of a xenograft having 1,098 +/- 276 fmol/mg protein of EGF receptor would either be stimulated by the administration of EGF or inhibited by the removal of the submandibular glands (sialoadenectomy) which contain a large amount of EGF. A miniosmotic pump containing 2 micrograms or 20 micrograms of EGF was implanted on the back of the animals in the EGF stimulation experiments. The tumor growth was stimulated by the administration of EGF (P < 0.01), and the doubling time of the tumor was reduced relative to the controls (P < 0.01). Both the mitotic indices and the bromodeoxyuridine (BrdU)-labeling indices of the tumor were higher than those of the controls (P < 0.01). Tumor growth inhibited by the sialoadenectomy (P < 0.05) while the tumor doubling time was prolonged compared with the sham-operated mice (P < 0.05). These results suggest that the growth of a human gastric cancer xenograft may be modulated by EGF.
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PMID:Stimulatory effect of EGF and inhibitory effect of sialoadenectomy on growth of an EGF receptor-hyperproducing human gastric cancer xenograft in nude mice. 798 44

Resected specimens of 288 primary stomach cancers (175 early cases and 113 advanced cases) and recurrent tumors or biopsy specimens of 21 recurrent or inoperable metastatic stomach cancers were examined immunohistochemically for expression of c-erbB-2 oncogene product. c-erbB-2 protein-positive staining was detected in 6.9, 15.9 and 28.6% of early, advanced and recurrent or inoperable metastatic stomach cancers, respectively, the difference being significant (p < 0.005). Four patients with advanced cancer showed positive staining in metastatic lymph nodes but not in the primary tumors. The results of tissue immunostaining were compared with c-erbB-2 protein levels in sera of the patients measured by an enzyme-linked immunosorbent assay. The levels of this oncogene product were consistently low in the sera of most of the patients with primary stomach cancers, regardless of whether or not c-erbB-2 protein was expressed in the tumor. However, in the recurrent or inoperable metastatic stomach cancers, 5 of 6 patients with c-erbB-2 protein-positive tumors showed elevated levels of c-erbB-2 protein in the serum. After following up c-erbB-2 protein levels in the sera of 3 patients during the period of chemotherapy against recurrent or inoperable metastatic disease, we found that the levels increased only in the late stage. These results suggest that, in stomach cancer, c-erbB-2 protein is likely to be excreted into the serum at a relatively late stage, reflecting systemic spread of the disease.
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PMID:Comparison of c-erbB-2 oncoprotein expression in tissue and serum of patients with stomach cancer. 799 90

The human c-erbB-2 protooncogene product (erbB-2 protein) is a 185 kilodalton glycoprotein closely related to epidermal growth factor receptor protein. In this study, we measured the concentration of circulating erbB-2 protein in cancer patients by means of a new immunoradiometric assay (IRMA). Two monoclonal antibodies (MoAbs), SV2-61 gamma and 6G10, recognize erbB-2 protein but bind to separate epitopes. SV2-61 gamma was used as an immunoadsorbent and 6G10 as an 125I-labeled probe. A serum was considered positive for erbB-2 protein if the percent binding exceeded the mean of the normal group by more than 3 standard deviations. Eleven of 21 patients with advanced breast cancer and 1 of 15 with advanced gastric cancer were positive. Serum erbB-2 protein levels correlated well with the therapy and the status of the patients with breast cancer. On the contrary, all patients with advanced colon, ovarian, or pancreatic cancers, showed levels below the cut-off value. These results suggest that circulating erbB-2 protein can be measured using the newly constructed IRMA. Since c-erbB-2 protooncogene amplification and overexpression are accepted as a good marker of aggressiveness, relapsing potency, and poor prognosis, this IRMA should be a promising tool with which to help manage breast cancer patients.
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PMID:Construction of immunoradiometric assay for circulating c-erbB-2 protooncogene product in advanced breast cancer patients. 809 2

We examined 32 cases of surgically resected stomach cancer for the immunohistochemical expression of p53 and c-erB-2 protein and correlated the findings with clinical outcome and established prognostic factors. p53 Was observed in the nuclei of tumor cells in 11 of 32 cases (33%) and c-erbB-2 immunoreactivity was observed in nine of 32 cases (27%). In eight cases both p53 and c-erbB-2 were positive; however, double immunostaining revealed that less than a third of the same tumor cells were positive for both p53 and c-erbB-2 in these cases. The immunohistochemical localization patterns of p53 and c-erbB-2 were not related to the histopathologic differentiation of the carcinoma cells. No correlation was observed between expression of p53 and/or c-erbB-2 and the clinical outcome and established prognostic factors, including clinical stage and histologic types of the tumor examined. These results indicate that abnormalities of p53 and c-erbB-2 may not play major roles in the biologic behavior of human stomach cancer and that abnormalities in p53 and c-erbB-2 do not necessarily occur simultaneously in the development of stomach cancer.
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PMID:Double immunostaining for c-erbB-2 and p53 in human stomach cancer cells. 809 38

This study was conducted to see whether the accuracy in predicting liver metastases in gastric cancer patients increased when DNA aneuploidy and c-erbB-2 gene products were analyzed besides other clinicopathologic features. Aneuploidy was observed in 32 out of 74 tumors (43%); these included 62% of those tumors in patients with liver metastases, 43% of those with peritoneal dissemination and 26% of those in the 5-year survival group. Aneuploidy was positively correlated with the prognosis and degree of blood vessel invasion but not with lymph node metastases or lymphatic permeation. Positive staining for the c-erbB-2 gene product was detected in 19 out of 89 tumors (21%). This staining was not related to any of the clinicopathologic features examined. Multivariate analysis revealed that the degree of blood vessel invasion was the factor that most strongly correlated with liver metastases. The prognostic value of aneuploidy was significant (p < 0.05) but much smaller than that of blood vessel invasion (p < 0.0001), interstitial tissue reaction (p = 0.02), Borrmann type classification (p = 0.03). Analyses of DNA aneuploidy and c-erbB-2 gene expression in the primary tumor of gastric carcinoma to improve the accuracy of predicting liver metastasis seem to be of limited clinical value at present.
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PMID:Predictive value of c-erbB-2 and DNA ploidy patterns in gastric carcinoma recurrence. 810 19

c-erbB-2 oncogene encodes a growth factor receptor whose amino acid sequence has extensive homology with human epidermal growth factor receptor. It is frequently overexpressed in human breast, ovary, lung, and stomach cancers, where its overexpression is related significantly to the prognosis. Tl investigate the possible role of c-erbB-2 oncogene in the oncogenesis of stomach cancer, we examined the genetic alterations of c-erbB-2 oncogene in 4 stomach cancer cell lines, SNU-1, SNU-5, SNU-16 and KATO III. There were no differences in c-erbB-2 mRNA level as well as c-erbB-2 gene copy number among them. But gp185-erbB-2, c-erbB-2 gene product, was increased from 2- to 4-fold in SNU-1 and SNU-5 cells, compared with that in SNU-16 or KATO III cells. Our results suggest that post-transcriptional regulation of gp185erbB-2 expression may underlie gp185erbB-2 overexpression in cancer cells.
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PMID:The mechanism of c-erbB-2 gene product increase in stomach cancer cell lines. 810 20

The mutational activation of the neu proto-oncogene was analyzed in schwannomas of the peripheral nervous system transplacentally induced by N-ethyl-N-nitrosourea (ENU) in rats. All nine primary schwannomas investigated contained a T-->A transversion mutation at nucleotide 2012 of the neu gene, leading to the substitution of valine to glutamic acid in the transmembrane domain. Loss of the wild-type allele occurred in five of nine (56%) primary schwannomas. All four ENU-induced schwannomas transplanted in syngenic hosts (2-14 passages) showed the T-->A transversion mutation and loss of the wild-type allele. These data suggest that mutation of one allele together with loss of the wild-type allele constitutes two critical steps in the progression of rat schwannomas. Since c-erbB-2, the human counterpart of the rat neu gene is frequently involved by amplification in the development of human gastric cancer [30], we screened 12 rat gastric carcinomas induced by N-methyl-N-nitrosourea (MNU) for mutations in the neu gene. However, none of these tumors contained mutations.
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PMID:neu mutations and loss of normal allele in schwannomas induced by N-ethyl-N-nitrosourea in rats. 833 Mar


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