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)

Twelve cases of ovarian adenocarcinoma were studied for alterations in proto-oncogenes, and a unique pattern of altered ras proto-oncogenes was observed. Amplification of ras-Ki was found in three of seven ovarian tumors and amplification of ras-Ha in one of 12. In contrast, ras-Ha amplification was not found in any of the 334 other tumors and ras-Ki amplification was only seen in breast cancer at a frequency of 3%. Other proto-oncogenes altered in ovarian adenocarcinomas included c-myc and c-erbb-2. Proto-oncogene abnormalities were more frequent in aggressive tumors of high histologic grade.
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PMID:A unique pattern of proto-oncogene abnormalities in ovarian adenocarcinomas. 316 70

The p21 protein product of the cellular oncogene ras, designated ras p21, has been detected immunohistochemically in normal, benign and malignant human thyroid tissues. With the monoclonal antibody RAP-5 generated against a synthetic peptide corresponding to amino acid positions 10 to 17 of the ras p21 protein and an avidin-biotin-peroxidase complex (ABC), the expression of the ras p21 was evaluated in paraffin-embedded sections. Western blot analysis using fresh thyroid carcinoma tissue revealed double protein bands, one band was at molecular weight 21,000 and the other was a more rapidly migrating band at the molecular weight 17,500. Immunohistochemically, papillary adenocarcinomas of the thyroid showed moderate to intense stainings for ras p21 in most cases. Cytoplasmic and apical surface stainings were the most common patterns of immunoreactivity. Adenomas showed variable ras p21 positivity in cytoplasm and apical surface stainings of adenomas were negative to borderline in most cases. The cytoplasm of tissues of Hashimoto's thyroiditis, Graves' disease, and normal thyroid tissues was uniformly ras p21 positive, but the apical cell surface was nonreactive for ras p21 in all tissues. Judging from the findings obtained on this large series of normal, benign, and malignant thyroid tissues, the elevation of ras p21 may be a common event in thyroid neoplasm, and especially elevated ras expression in the apical cell surface may be characteristic to papillary carcinomas of the thyroid. This suggests that apical surface expression of ras p21 may be important in the development of thyroid carcinomas and be useful in differentiation of papillary adenocarcinoma.
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PMID:Immunohistochemical demonstration of ras p21 oncogene product in normal, benign, and malignant human thyroid tissues. 327 92

The expression of ras oncogene product p21 in human malignant pleurisy and primary lung cancer was studied immunocyto-histochemically with monoclonal antibodies (MoAbs) rp-28 and rp-35 against ras p21. In pleural effusion cells, cancer cells revealed more intensively positive reaction with MoAb rp-35 than with MoAb rp-28, especially in the plasma membrane, and no positive reaction was obtained in any kind of inflammation cells with the exception of faintly positive reaction in the cytoplasm of macrophages. In primary lung cancers, well or moderately differentiated adenocarcinoma tissues showed higher reactivity with MoAb rp-28 than those of poorly differentiated adenocarcinoma or any other histological subtype of lung cancer. With MoAb rp-35, intensively positive reaction was obtained in most of cases with all different histological subtypes of lung cancer. The staining in cancer cells was usually localized intensively to the plasma membrane and weakly to the cytoplasm with both MoAbs. Normal bronchial epithelial and glandular tissues showed only cytoplasmic staining. These two MoAbs, especially MoAb rp-35, may be useful in clinicopathological applications for the diagnosis of malignant pleurisy and primary lung cancer.
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PMID:Immunohistochemical analysis of human lung cancers with anti-ras p21 monoclonal antibodies. 333 May 57

Tumour-cell heterogeneity has been studied in a continuous cell line, UCRU-BL-17CL, established from a xenografted human primary bladder carcinoma. The cell line, grown in vitro for more than 30 generations, reflects the pathology of both the xenograft from which it was derived and the original human tumour. It comprises mainly adenocarcinoma cells which secrete mucin in vitro, as well as squamous and transitional carcinoma cells. Features of both adenocarcinomatous and squamous differentiation have been observed within the same cell. The line expresses ABH blood group isoantigens, binds to peanut lectin and reacts with monoclonal antibodies (MAbs) raised against keratin and against normal and malignant epithelial cells. It also reacts with MAbs against ras p21 proteins and the epidermal growth factor receptor (EGFR). It shows high levels of lactic acid dehydrogenase isozyme 5, consistent with a high-grade tumour, forms colonies in methylcellulose and is tumorigenic in nude mice. The karyotype (human) shows many marker chromosomes, consistent with expression of EGF receptors and ras p21 proteins, and an 11:13 translocation. DNA content, as studied by flow cytometry, reveals a shift from tetraploid to near triploid. This line may provide a useful model for studies of the histogenesis of bladder cancer and the relationship between transitional-cell carcinoma and the other histological subtypes of this disease.
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PMID:Establishment and characterization of a new human bladder cancer cell line showing features of squamous and glandular differentiation. 333 21

In order to investigate the value of ras oncogene expression as a prognostic indicator in rectal adenocarcinoma, we evaluated the level of ras gene protein product (p21) in the available material of 149 consecutive Dukes' B and C specimens resected at our institution between 1965 and 1981. Five year follow-up was available in all patients. Pathology slides and archival paraffin blocks were retrieved for confirmation of the original diagnosis, study of histopathological features, 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 giving definitive staining using the avidin-biotin peroxidase method. The analysis indicated that the group of tumors with high (greater than or equal to 1:40,000) p21 titers had a worse 5-year survival (43.9 versus 64.3%, P less than 0.02), higher incidence of distant metastases (51.8 versus 23.2%, P less than 0.001), and more advanced Dukes' stage (53.7 versus 35.7% incidence of Dukes' C stage, P less than 0.04) than tumors with low (less than 1:40,000) titers. Multivariate analysis also demonstrated that the influence of the level of ras gene protein product on survival was independent of Dukes' stage. We conclude that detection of high levels of ras oncogene protein product indicates a group of tumors with a more aggressive behavior, characterized by a higher percentage of distant recurrences and worse prognosis. These findings suggest that measurement of p21 may become clinically important in identifying patients at high risk of recurrent disease.
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PMID:Ras oncogene expression as a prognostic indicator in rectal adenocarcinoma. 339 89

During the course of studies designed to assess the effect of human Ha-ras gene expression on the malignant behavior of transfected mouse tumor cells we noted that the process of Ca3(PO4)2-mediated DNA transfection was itself associated with profound alterations in tumorigenic or metastatic behavior. The cell line used as a recipient for these studies was a tumorigenic nonmetastatic CBA/J mouse mammary adenocarcinoma line called SP1. When cotransfected with plasmids containing the neo gene (pSV2neo) and the activated Ha-ras gene (pT24-c3), cells from the pooled (5-10 colonies) G418-resistant colonies gave rise to spontaneous lung metastases in 85% of mice after subcutaneous inoculation. However, we noted that 17% of control mice inoculated with G418-resistant pSV2neo-transfected SP1 cells also had lung metastases and that this number approached 100% as the inoculum comprised a greater pool size (50-100 colonies). When cell lines established from isolated pSV2neo-transfected colonies were examined, 3/16 were found to be metastatic. We also found that 3/16 clones grew slowly, or not at all, in CBA/J mice, whereas they grew readily in athymic (nude) mice. The increase in immunogenicity of two out of three of these latter clones was accompanied by expression of the class I H-2Dk major histocompatibility complex antigen that was not detectable in the parental SP1 cells. At least some of these results would appear to be due to exposure to Ca3(PO4)2 alone, as we found that it resulted in 5/20 (25%) clones manifesting metastatic properties. Our results suggest that heritable changes in malignant behavior of transfected tumor cells can be observed at high frequency subsequent to the process of Ca3(PO4)2-mediated DNA transfection, and these changes may be brought about in part by inherited disturbances in expression of recipient cell genes.
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PMID:Alteration of the tumorigenic and metastatic properties of neoplastic cells is associated with the process of calcium phosphate-mediated DNA transfection. 346 68

Several crypt abnormalities have been demonstrated in the mucosa of neoplastic and preneoplastic lesions of the large intestine. In addition, certain tumor markers are expressed in large intestinal carcinoma but not in normal mucosa. To determine whether any correlation exists between tumor marker expression and crypt abnormalities and at what stage markers are expressed, we studied specimens of large intestinal mucosa from 13 patients with preneoplastic conditions (adenomatous polyp, familial polyposis, Crohn's disease, and ulcerative colitis). The tumor markers examined include carcinoembryonic antigen (CEA), the ras gene products p21 and p21ser (mutated form), and beta-D-galactosyl-(1----3)-alpha-N-acetyl-D-galactosamine (gal--gal NAc, also known as T-antigen). Results were compared to those of five cases of adenocarcinoma of colon and three control cases of colonic mucosa obtained at immediate autopsy. All four markers were expressed in three of the five cases of adenocarcinoma, but none were expressed in the control cases. Variable expression of each marker was demonstrated in the dilated, distorted crypts of preneoplastic lesions. CEA and gal--gal NAc appeared to be expressed most frequently, suggesting that these are common markers or are expressed at an earlier stage in the neoplastic process than p21 or p21ser. Demonstration of such markers in preneoplastic conditions may be of use in determining the malignant potential and in monitoring these lesions.
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PMID:Expression of carcinoembryonic antigen, T-antigen, and oncogene products as markers of neoplastic and preneoplastic colonic mucosa. 350 Jan 9

Two monoclonal antibodies were applied to benign, dysplastic, and malignant human colorectal tissues using immunohistochemical techniques on formalin fixed paraffin embedded material. RAP-5 antibody is directed against a synthetic peptide, reflecting an amino acid sequence of the ras oncogene p21 protein product. Despite using several different techniques and antibody dilutions differential staining between the various epithelial populations was not obtained. RAP-5 also showed other tissue components such as plasma cells, histiocytes, fibroblasts, smooth muscle and vascular endothelium. CA19-9 antibody recognizes an epithelial surface carbohydrate antigen originally derived from a human colorectal carcinoma cell line: it did not stain normal colorectal mucosa or adenomatous polyps, but showed focal expression of variable strength in regenerative, dysplastic, and cancerous mucosa in ulcerative colitis, and in non-colitic colorectal carcinoma. Neither antibody was found to be a reliable marker of the evolution of malignant mucosal changes, although CA19-9 may be of limited use in confirming adenocarcinoma of gastrointestinal origin.
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PMID:Immunohistochemical staining of colorectal tissues with monoclonal antibodies to ras oncogene p21 product and carbohydrate determinant antigen 19-9. 354 94

This report documents that the pancreatic adenocarcinoma cell line, HPAF, contains oncogene activity detected by transformation of NIH 3T3 cells through transfection with HPAF DNA. The HPAF transfected NIH 3T3 cells do not contain oncogenes homologous with c-H-ras, c-K-ras, c-N-ras, v-fms, c-myb, c-sis, v-fgr, c-mos, c-myc, c-fos, v-fes, v-src, v-erb A, v-erb B, c-N-myc, v-raf, or v-abl, other than the endogenous mouse genes. The transfectants do express proteins detected by two-dimensional sodium dodecyl sulfate-polyacrylamide gel electrophoresis which were not found in nontransfected NIH 3T3 cells. Monoclonal antibodies raised against the transfectants recognize proteins not found in untransfected NIH 3T3 cells that are antigenically identical to proteins found in the HPAF cells. These antigens are also detected on six other human pancreatic adenocarcinoma cell lines but show a much more restricted distribution on lymphoblastoid, melanoma, prostatic carcinoma, and normal skin fibroblast cell lines.
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PMID:Antigens expressed on NIH 3T3 cells following transformation with DNA from human pancreatic tumor. 369 88

We have analyzed the mechanism of activation of two human ras oncogenes. We have also identified a rasN gene from a human gastric adenocarcinoma which efficiently induced both morphological transformation and tumorigenicity of NIH3T3 cells in a transfection assay. The rasN gene in tumor tissue DNA did not appear to be rearranged or amplified. A molecular clone, which contained an EcoRI fragment spanning the first and second rasN exons, was molecularly cloned directly from the human tumor DNA. Chimeric constructions and DNA sequencing defined the mechanism of activation of the gene as a mutation in the 61st amino acid codon substituting arginine for glutamine. Normal DNA isolated from Epstein-Barr virus immortalized lymphocytes derived from the same patient did not induce morphological transformation or tumorigenicity in NIH3T3 cells. A cloned cell line isolated from the human pancreatic carcinoma cell line Panc1 had previously been shown to contain an activated rasK-2. Sequence analysis of the cloned transfected gene reveals a G to A change within codon 12, which is presumably responsible for its biological activity. This represents the first identification of a codon 12 aspartic acid substitution of a c-rask oncogene from a human tumor-derived cell line.
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PMID:Mechanism of activation of human ras genes cloned from a gastric adenocarcinoma and a pancreatic carcinoma cell line. 373 Nov 20


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