Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0007097 (carcinoma)
152,788 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Treatment of NIH 3T3 cells with interferon (IFN) after transfection with human bladder carcinoma EJ/T24 c-Ha-ras1 oncogene DNA caused inhibition of ras-induced cell transformation. Furthermore, the effect of IFN on oncogene expression in an established tumor line was studied. A tumor line of NIH 3T3 (RS485) was transformed by human c-Ha-ras1 activated by a viral long terminal repeat. Treatment of the tumor cells with IFN was associated with a progressive appearance of reverted, flat colonies which exhibited a normal phenotype with respect to morphology and growth. The revertants were well spread, contact inhibited cells; they did not grow in soft agar and were not tumorigenic in nude mice. Revertants retained their normal phenotype, although they contained transfecting human c-Ha-ras1 DNA; but, they produced significantly decreased levels of the onc-encoded protein p21 and c-Ha-ras1 mRNA as compared to RS485 cells.
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PMID:Interferon-induced modulation of human ras oncogene expression. 241 51

Using c-Ha-, c-Ki-, and c-N-ras-specific probes in a RNA-RNA hybridization assay we found enhanced expression of c-Ha-ras protooncogene in stomach adenocarcinomas relative to nonneoplastic epithelium, whereas little or no transcription of either c-Ki- or c-N-ras was detected. Enhanced levels of c-Ha-ras RNA expression were detected in all of the adenocarcinomas examined. Hybridization with c-Ha-ras was also detected in nonneoplastic gastric epithelium adjacent to carcinoma, although the labeling was less intense than that of carcinoma cells. More extensive analysis of the c-Ha-ras p21 expression was then carried out in formalin-fixed, paraffin-embedded tissue sections and extracts from surgically resected stomach tissues using monoclonal antibodies (MAbs) RAP-5 and Y13-259. The data obtained from the immunohistochemical studies were consistent with the results of in situ hybridization assay. Adenocarcinomas were much more reactive with MAb RAP-5 than benign and normal tissues, and the majority of carcinomas demonstrated increased expression of c-Ha-ras p21. Quantitative liquid competition radioimmunoassays using MAb Y13-259 also demonstrated significantly higher levels of c-Ha-ras p21 in extracts from stomach adenocarcinomas than those from normal mucosae. No strict correlation was found between ras p21 expression and the degree of tumor differentiation or histological type. Although advanced carcinomas generally demonstrated higher levels of ras p21 than early carcinomas, no correlation among advanced carcinomas and ras p21 levels was observed in relation to depth of tumor invasion to the muscularis propria, subserosa, or serosa. Benign lesions, in comparison, were much less reactive with MAb RAP-5 than carcinomas. Among the benign lesions tested, dysplastic lesions were more reactive than nondysplastic lesions. Normal stomach mucosa was generally nonreactive with the exception of parietal cells. Our results indicate that transformation of the stomach mucosa from benign to malignant phenotype is associated with an increase in c-Ha-ras p21 expression.
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PMID:Enhanced expression of c-Ha-ras p21 in human stomach adenocarcinomas defined by immunoassays using monoclonal antibodies and in situ hybridization. 243 16

The immunohistochemical localization of human chorionic gonadotropin (HCG) and alpha-fetoprotein (AFP) was studied in 44 cases with cholangiocarcinoma (CC) to determine the correlation to the expression of ras oncogene product p21 on tumor cells. HCG-immunoreactivity was found in 10 of 44 cases (23%) and AFP in only one (2.3%), whereas the expression of ras p21 was demonstrated in 39 (88.6%). The incidence of HCG-positive cells within the tumor was less than 1% in 8 of 10. The incidence of AFP-positive cells was less than 0.01%. All were histologically classified as adenocarcinoma and none of them had histologic features of trophoblastic tumors, yolk sac tumor or hepatocellular carcinoma. Nine of 10 HCG-positive and one AFP-positive CC expressed ras p21 on their tumor cells. However, one HCG-positive CC was negative for ras p21, though the incidence of HCG-positive cells within the tumor was 25%. HCG- and AFP-immunoreactivity was more frequently observed in poorly or undifferentiated tumor cells than in moderately or well-differentiated areas, whereas the expression of ras p21 was more diffuse in well-differentiated tumor and stronger in moderately differentiated areas, but rarely found in poorly and undifferentiated tumor. These results suggest that HCG production by CC of the usual adenocarcinoma variety is not rare, when compared to AFP production, and is preferentially localized in a small number of poorly differentiated and undifferentiated carcinoma cells, and there is no correlation between the production of HCG or AFP and the expression of ras p21 in CCs.
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PMID:Human chorionic gonadotropin and alpha-fetoprotein in cholangiocarcinoma in relation to the expression of ras p21: an immunohistochemical study. 247 36

We carried out clinicopathological and immunohistochemical studies on tissues from 96 patients with pancreatic carcinoma, excluding cystic neoplasms (cystadenocarcinomas). The cumulative three-year survival rate was 8.8%, and 58 patients (60.4%) died within one year of the initial surgery. The survival curves for patients with pancreatic carcinoma with no venous invasion and no lymph node metastasis were significantly more favorable than for those with venous invasion and/or lymph node metastasis. The curves for patients with well-differentiated adenocarcinoma were significantly more favorable than for those with moderately or poorly differentiated adenocarcinoma. Fifteen patients with small pancreatic carcinomas, the greatest diameter being less than 3 cm, had more favorable postsurgical outcomes, with a cumulative two-year survival rate of 45%, compared to 81 patients with more advanced carcinomas, with a rate of 11% (P less than 0.05). In the majority of cases, the tumor contained carcinoembryonic antigen, carbohydrate antigen 19-9 and Ha-ras p21 immunoreactants in cell membranes or cytoplasm of the cells and/or in the stroma. There was no significant relationship between the immunohistochemical results and the clinical outcome.
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PMID:Carcinoma of the pancreas: a clinicopathologic study of 96 cases with immunohistochemical observations. 253 6

The injection of a retrovirus carrying the v-ras-Ki oncogene into the thyroid gland of adult Fischer rats induces thyroid carcinomas when associated with a treatment of the animals with a goitrogenic agent. More than one hundred adult Fischer rats have been treated with the goitrogen agent propylthiouracil in order to induce thyroid hyperplasia. Twenty days after treatment, rat thyroid glands, surgically prepared, were injected with the Kirsten murine sarcoma virus (KiMSV). Within three months more than 90% of the animals developed thyroid tumors. Histologically the tumors had the appearance of well differentiated carcinomas. Thirty animals had lung metastases in addition to the thyroid carcinoma. The presence of KiMSV specific transcripts and the specific transforming protein (p21) in thyroid carcinomas and in the metastases was detected by Northern blot analysis and immunoprecipitation, respectively. Only three rats, among thirty that had not received the goitrogen treatment, but only the injection with KiMSV, developed thyroid carcinomas of very small size and with a very long latency period (almost one year). The results described represent the first instance of thyroid carcinoma induction by retroviruses. This system may be regarded as a useful model to investigate the process of thyroid carcinogenesis in vivo. These results suggest that this model may also be useful for investigating the interaction between hormones and cells harboring the activated oncogene in the development of thyroid carcinoma since activated ras oncogenes have been implicated in human thyroid carcinoma.
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PMID:The Kirsten murine sarcoma virus induces rat thyroid carcinomas in vivo. 253 91

Alteration of oncogene and loss of chromosomal heterozygosity are infrequent in human gastric carcinoma compared with those in other gastrointestinal carcinomas. Amplification of c-erbB-2 gene is observed in well differentiated adenocarcinoma, while sam gene is found in poorly differentiated adenocarcinoma or scirrhous carcinoma. sam gene, which was isolated from a gastric cancer cell line KATO-III by a DNA renaturation method, encodes tyrosine-specific protein kinase domain. A good correlation evidently exists between the synchronous expression of TGF alpha and ras p21 and biological malignancy of gastric carcinoma. c-myc and c-fos proteins are found not only in tumor cells but also in stromal cells including macrophages and fibroblast around the tumors. The prognosis of patients with c-myc p 62-positive stromal cells is significantly better than that of patient with p 62-negative stromal cells. Coamplification of the hst-1 gene and int-2 is observed in 50% of primary tumors and all metastatic tumors of esophageal carcinoma. PCR (polymerase chain reaction) technique seems to be useful for the detection of oncogene point mutation in human gastric carcinoma.
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PMID:[Oncogenes in human gastric carcinoma]. 254 46

The expression of the ras gene product p21 in normal gastric mucosa, early gastric carcinoma of diffuse (gastric) and intestinal types, and in adjacent mucosal abnormalities is reported. The analysis was performed on paraffin sections by an immunohistochemical assay using the mouse monoclonal antibody RAP-5 and the rat monoclonal antibody Y13-259. Expression of ras p21 was assessed by staining intensity and percentage of positively stained cells. In comparison to normal gastric mucosa of non-cancer patients, p21 was overexpressed in nearly all early carcinomas of both types and in the dysplastic and/or metaplastic mucosal alterations accompanying intestinal type of gastric cancer. Increased p21 expression was also observed in the normal-appearing mucosa adjacent to early carcinomas of diffuse type, but not in the morphologically normal gastric epithelium adjacent to the intestinal type. The results of this investigation suggest that ras p21 overexpression may be related to early events of human gastric carcinogenesis. The study supports the notion of different pathways in the development of diffuse (gastric) and intestinal types of gastric carcinomas.
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PMID:Expression of ras oncogene p21 protein in early gastric carcinoma and adjacent gastric epithelia. 255 Jan 23

Aberrant proto-oncogene expression has been implicated in hepatic cell proliferation, transformation and carcinogenesis using a rat model. To investigate the role of ras p21 product expression in human hepatocellular carcinoma (HCC), we have localized ras p21 in formalin fixed, paraffin-embedded normal and abnormal livers utilizing the avidin-biotin peroxidase method and a monoclonal antibody to ras-gene product p21. A semi-quantitative estimate of p21 expression was performed by serial dilutions of primary antibody. While low dilutions of anti-p21 stained normal hepatocytes, higher dilutions failed to react with normal hepatocytes and these dilutions were used for assessment of p21 enhancement. Increased p21 expression of ras oncogene in HCC occurs in fibrolamellar carcinomas and other better differentiated HCC. Tumor dedifferentiation is associated with an attenuation of p21 expression. Liver adjacent to HCC exhibits p21 enhancement, in contrast to liver surrounding metastatic carcinoma, suggesting increased p21 expression in HCC induction.
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PMID:ras oncogene p21 expression in hepatocellular carcinoma. 255 Jun

It is well known that many of thyroid carcinoma are capable of responding to TSH, but our studies shown that there are some alteration in this responsiveness. The adenylate cyclase responsiveness to TSH was usually greater in thyroid carcinoma than in adjacent histologically normal thyroid tissue. The level of increased response of adenylate cyclase were correlated with the level of enhanced expression of ras oncogene product p21 assessed by Western blotting analysis. The TSH induced desensitization of adenylate cyclase was not observed in some differentiated carcinoma. This loss of desensitization may be reflect the change in ADP-ribosylable Gi protein. In the differentiated carcinoma, the capacity of EGF receptor was higher than that in normal thyroid. The EGF binding to cultured carcinoma cells did not increase in response to TSH. These altered properties of transmembrane control in human thyroid carcinoma may be related to the neoplastic growth.
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PMID:[Transmembrane controls in cultured human thyroid carcinoma]. 256 2

The expression of ras, c-myc and c-erbB-2 oncoproteins in 100 human (73 ductal and 27 lobular) breast carcinomas has been examined using an immunohistochemical analysis. The monoclonal antibody Y13 259 has been used for the ras p21, the monoclonal antibody Myc1-9E10 for the c-myc p62 and the polyclonal antibody pAb1 (from Triton Bioscience Inc.) for the c-erbB-2 p185 oncoproteins. The following conclusions can be drawn from the analysis: Of the 100 breast carcinoma cases studied only 14 did not express any of the three oncogenes. The remaining 86 were positive for one or more of the three oncoproteins. Ductal carcinomas expressed oncoproteins in 92% of the cases (67/73), whereas lobular carcinomas expressed them in 70% of the cases (19/27). The most frequently expressed was c-myc p62 in 70% of cases followed by ras p21, 55% and c-erbB-2, 35%. Elevated expression of ras, myc or erbB-2 oncogenes did not correlate with the presence of metastasis in auxiliary lymph nodes, the numbers of infiltrated lymph nodes the grade of the tumor or hormone status. However, there appears to be a correlation between increased ras staining intensity and patient's age, below 50 years.
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PMID:ras, c-myc and c-erbB-2 oncoproteins in human breast cancer. 257 23


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