Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0001418 (adenocarcinoma)
 68,496 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The role of cellular oncogenes in the development of epithelial tumors of the human female reproductive tract has not previously been extensively studied. DNAs isolated from ten human uterine, 13 ovarian, and four cervical neoplasms and from three cell lines derived from endometrial adenocarcinoma were investigated by dot blot hybridization after polymerase chain reaction amplification of ras gene sequences and in some cases by NIH 3T3 transfection. Transforming activity was found in two of nine endometrial adenocarcinomas, but none of seven ovarian carcinomas and none of four cervical carcinomas showed transforming activity. K-ras sequences with a GGT----GAT mutation in codon 12 were demonstrated in both transformants derived from endometrial carcinoma. K-ras codon 12 mutations were similarly detected in six of 13 endometrial carcinomas (one GAT and GCT, one GTT and GCT, two GAT, two GTT) and two of 13 ovarian tumors (GAT and GCT, GAT), both mucinous adenocarcinomas. Point mutation of K-ras in codon 12 is thus comparably frequent in uterine endometrial carcinomas and in colorectal carcinomas and may have similar significance as an event that contributes to progression of these tumors. Cervical carcinomas and ovarian tumors in general, with the possible exception of mucinous adenocarcinoma of the ovary, do not appear to have this characteristic.
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PMID:K-ras activation in neoplasms of the human female reproductive tract. 220 77

Point mutations at codons 12, 13, or 61 of the Ha-, Ki-, and N-ras genes are able to convert these normal cellular genes into activated oncogenes. Previous studies have shown that ras gene mutations occur in a variety of human solid tumors and may be important in the pathogenesis of some of these tumors. In order to test the hypothesis that ras gene mutations may be associated with prostate cancer, we have used an oligodeoxynucleotide hybridization assay to detect wild-type and mutant alleles in genomic DNA from prostate tumors and prostate tumor cell lines amplified using the polymerase chain reaction. Twenty-four primary prostate tumors (23 acinar tumors and one ductal tumor) and five prostate tumor cell lines were examined for mutations at codons 12, 13, and 61 of the Ki-ras, Ha-ras, and N-ras genes. Two mutations were detected: an A----G transition causing a glutamine to arginine amino acid substitution at codon 61 of the Ha-ras gene in a primary prostatic duct adenocarcinoma and a G----T transversion causing a glycine to valine amino acid substitution at codon 12 of the Ha-ras gene in a prostate tumor cell line (TSU-PR1) derived from a lymph node metastasis. While the overall frequency of ras gene mutations in prostate tumors is low, when these mutations do occur they may have a role in the progression of disease or the development of the unusual ductal variant of prostatic adenocarcinoma.
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PMID:ras gene mutations in human prostate cancer. 220 48

In A/J strain mice, the carcinogen urethan induces lung adenomas and adenocarcinomas that contain Ki-ras-activating mutations primarily in codon 61. These mutations affect the middle adenine in codon 61 resulting in the substitution of either arginine (AT----GC transition) or leucine (AT----TA transversion) for the wild-type glutamine. To analyze the expression of the wild-type and mutant Ki-ras mRNAs in primary mouse lung tumors and transformed mouse lung cell lines, we utilized reverse transcription of total mRNA and DNA amplification by the polymerase chain reaction. The wild-type allele of codon 61 was expressed in all normal lung and primary tumor samples and in all transformed cell lines, except one. Significantly, the leucine-substituted allele was expressed primarily in very small lung adenomas, whereas the arginine-substituted allele was expressed in large lung adenocarcinomas and transformed lung cell lines. The relative amounts of expression of the mutant versus wild-type Ki-ras alleles and the total Ki-ras mRNA expression was similar in both lung adenomas and adenocarcinomas. Further, the arginine mutant allele was present in adenocarcinomas having either alveolar or papillary tumor morphologies. These results suggest that the specific activating Ki-ras mutation is more critical to either lung adenoma or adenocarcinoma development than is the tumor's cell of origin or the extent to which the mutant alleles are expressed. A distinct role of the specific activating Ki-ras mutations in affecting lung tumor growth or malignant potential is indicated.
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PMID:Specific Ki-ras codon 61 mutations may determine the development of urethan-induced mouse lung adenomas or adenocarcinomas. 224 61

The three well-characterized genes of the ras gene family H-ras, K-ras, and N-ras, code for closely related 21-kD proteins that have a role in the transduction of growth signals. The ras proteins acquire transforming potential when a point mutation in the gene leads to replacement of an amino acid in one of the critical positions 12, 13, or 61. Overexpression of the normal protein, usually associated with gene amplification, can have similar effects. The detection of mutationally activated ras genes has been facilitated by the development of oligonucleotide hybridization assays that allow the identification of each possible mutation at the critical sites. Employment of the polymerase chain reaction has greatly increased the sensitivity of these assays. Studies of human lung cancer have shown that adenocarcinoma is the only subtype associated with ras mutations. These occur in about 30% of primary tumors. In almost all cases, the mutation is present in codon 12 of the K-ras gene. No mutations have been observed to date in tumors of nonsmokers, suggesting that the mutation may result from exposure to carcinogenic ingredients of tobacco smoke. Amplifications of ras genes were shown to be very uncommon in clinically early stages of lung cancer. Analysis of the clinical data of patients who were operated on for adenocarcinoma of the lung shows that K-ras mutations are not associated with particular histologic characteristics of the tumors or with specific presenting features. Patients with K-ras mutations, however, had significantly worse survival than did those without an activation.
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PMID:The ras oncogenes in human lung cancer. 225 72

In order to evaluate the relevance of protooncogene alterations in gastric cancer and to specifically relate these alterations to types and stages of the neoplasia, we studied oncogenes of possible interest in gastric tumors with different clinical parameters. Fifty DNAs from primary gastric adenocarcinoma were analyzed, by the Southern blotting technique, for the presence of amplification or rearrangements of seven different protooncogenes: c-myc, c-erbB2, c-Ki-ras, c-Ha-ras, c-N-ras, hst, and c-mos. All the tumors analyzed were histologically classified and staged. Amplification of the following genes was found: c-myc (2 of 50), hst (3 of 50), c-erbB2 (3 of 50), and c-Ki-ras (5 of 50). The simultaneous amplification of hst (3 cases), c-myc (1 of 3), or c-Ki-ras (2 of 3) was observed. Analysis of DNAs from atrophic and metaplastic gastric mucosa (which can be regarded as preneoplastic lesions) of the 10 patients showing gene amplification demonstrated that this was limited to neoplastic cells. Considering protooncogene amplification in general (i.e., involving different genes and occurring to different degrees) and clinical parameters of tumors, we found a statistically significant association between amplification and both tumor progression and presence of metastases. Therefore, at least for the genes analyzed, amplification is a relatively infrequent phenomenon and represents a late event in the temporal development of gastric cancer.
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PMID:Heterogeneous protooncogene amplification correlates with tumor progression and presence of metastases in gastric cancer patients. 225 24

In order to investigate the value of ras oncogene expression as a prognostic indicator in colonic adenocarcinoma, we evaluated the level of ras gene protein product (p21) in the available material of 109 surgical specimens resected at our institution between 1978 and 1981. Pathology slides and archived paraffin blocks were retrieved for confirmation of the original diagnosis, determination of stage, and measurement of p21 content. P21 titers were obtained using the RAP-5 monoclonal antibody in a semiquantitative immunohistochemical assay. Titer was expressed as the highest dilution of antibody given definitive staining using the Avidin-Biotin peroxidase method. The analysis indicated that tumors with high (greater than or equal to 1:40,000) p21 titer had a lower five-year survival rate than tumors with low (less than 1:40,000) titers (34.3% vs 60.8%, p less than 0.02). When a logistic regression analysis was used with the dependent variable being five-year survival and the independent variables being age, sex, location of tumor. Dukes' stage, mucin production, p21 titer, differentiation degree and tumor size, the statistically significant relationship of the level of ras gene protein product to long-term survival was negated by the concomitant knowledge of Dukes' stage. On the other hand, when only the variables available in the preoperative period were entered in the multivariate analysis, p21 titers retained a significant relationship with long-term survival (p less than 0.05). We conclude that ras oncogene determination in colonic carcinomas may have clinical importance for the pre-operative identification of a group of colonic tumors with a more aggressive behavior and a poorer prognosis.
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PMID:Relationship between ras oncogene expression and clinical and pathological features of colonic carcinoma. 225 30

Formalin-fixed paraffin-embedded tissue specimens obtained by fine needle aspiration of pancreatic masses from 47 patients were examined retrospectively for cytology and the presence of mutant c-K-ras oncogenes. Point mutations of c-K-ras in codon 12 were detected by RNA-DNA RNAse A mismatch cleavage after in vitro DNA amplification of the cellular c-K-ras sequences by the polymerase chain reaction. Of the 36 patients with pancreatic adenocarcinoma, mutant c-K-ras oncogenes were detected in 18 of 25 (72%) with malignant cytologies, 2 of 8 (25%) with atypical cytologies, and 0 of 3 with benign aspiration cytologies. The remaining 11 patients without pancreatic adenocarcinomas did not have mutant c-K-ras genes detectable by the assay. The diagnosis of pancreatic adenocarcinoma was based upon clinical follow-up. The presence of mutant c-K-ras oncogenes did not significantly affect survival in the patients studied. Mutant c-K-ras genes were found at the time of initial clinical presentation in the majority of pancreatic adenocarcinomas, suggesting an important role of the mutation in oncogenesis. In conjunction with cytology, our approach represents an application for cancer diagnosis at the molecular genetic level.
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PMID:Detection of c-K-ras mutations in fine needle aspirates from human pancreatic adenocarcinomas. 240 91

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

Activation of c-ras oncogenes has been implicated in human carcinomas of the colorectum, prostate, bladder and breast. The major peptide product of c-ras is a 21 kilodalton peptide (p21), but other larger "ras-related" peptides have been described in urine obtained from patients with several types of cancers. In the present investigation immunohistochemical methods were used to assess c-ras expression in tissues obtained from patients with endometrial adenocarcinoma. Formalin-fixed, paraffin-embedded tissues were processed in routine fashion, then incubated with a monoclonal antibody raised against a v-H-ras synthetic peptide. ras Peptides were not detected in proliferative or secretory endometrium or in benign adenomatous hyperplasia. One of four specimens of atypical adenomatous hyperplasia and two of 11 specimens of grade 1 (international Federation of Gynecology and Obstetrics) adenocarcinoma stained positive for ras peptides. A total of 95% of the grade 2 and 3 adenocarcinoma studied contained detectable ras peptides within neoplastic cells. In contrast to previous immunohistochemical studies that identified ras peptides only in neoplastic cells of bladder, prostate, colon, and breast cancers, we routinely found ras peptides within stromal cells of high-grade endometrial carcinomas. When stained with hematoxylin and eosin, these cells have the appearance of foamy macrophages.
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PMID:ras oncogene is expressed in adenocarcinoma of the endometrium. 246 92

Metastatic (ASML 14-1, ASmv) and non metastatic (AS17-4) cell lines of the rat BSp73 pancreatic adenocarcinoma were investigated for amplification and expression of oncogene DNA. The c-myc gene was amplified, but only in one metastatic variant, ASML. The degree of amplification (3.5-fold) increased after prolongued in vitro cultivation (17.5-fold). All three tumor cell lines expressed c-myc and ras mRNA. Ras expression was at the same level as in rat liver. C-myc expression was considerably above the level in rat liver, but also differed considerably between the metastatic variants. In the metastatic ASML cells the c-myc gene was localized by in situ hybridization on a marker chromosome derived from chromosome 7. The karyotypes of the metastatic variants are different and have no common marker chromosomes. Our results obtained with the BSp73 tumor model do not support a role of the c-myc gene in the metastatic process.
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PMID:Amplification, expression and localization of the c-myc gene in BSp73 rat tumor cell lines. 246 34


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