Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Colonic epithelial tumors (101) including villoglandular adenomas, carcinomas in situ, adenocarcinomas, and neuroendocrine (NE) carcinomas were studied immunohistochemically with monoclonal antibodies (MoAb) RAP-5 and RAS-10 recognizing altered and unaltered ras oncogene products. In addition, 20 samples from multiple polyposis including adenomas with and without dysplasia, carcinomas in situ, and invasive carcinomas were studied. Using immunostaining techniques, normal mucosa was weakly stained, whereas the mucosa in the vicinity of tumors or inflammation showed enhanced staining. More tumors stained intensely with MoAb RAP-5 than with MoAb RAS-10. With MoAb RAP-5, most benign and malignant tumors showed enhanced staining. No significant differences in staining were noted in relation to superficial versus deeply invasive carcinomas or clinical staging. Immunostaining was also noted in some metastases. No significant differences in enhanced staining were found in carcinomas. Interestingly, the most extensive and enhanced immunostaining was noted in the villoglandular adenomas, dysplastic adenomas, and carcinomas in situ. The authors conclude that (1) ras protein expression is detectable in most benign, borderline, and malignant epithelial tumors of the colon as determined with MoAb RAP-5 and RAS-10, whereas enhanced expression is more often detected with RAP-5; (2) enhanced ras product expression in colon carcinomas does not seem to correlate with advanced tumor stages or with exocrine, NE, or phenotypically mixed tumors; and (3) the finding of the most intensely enhanced ras products expression in villoglandular polyps and carcinomas in situ suggests a possibly significant role for the oncogene in the early phases of transformation.
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PMID:An immunohistochemical analysis of ras oncogene expression in epithelial neoplasms of the colon. 240 34

We have previously examined the expression of the Harvey-ras (Ha-ras) oncogene related transcripts in human malignant breast tumors and in their respective normal tissue [Spandidos and Agnantis, Anticancer Res. 4: 269-272, 1984]. Our results revealed a significant elevation of Ha-ras transcripts in malignant compared to normal tissue. In the present follow-up study we have examined the relationship of Ha-ras oncogene expression to the various clinicopathological parameters of these tumors. Although elevated expression was observed in all breast tumors as compared to their respective normal breast tissue there was no correlation with the tumor stage as defined by the TNM system. However, several correlations between Ha-ras oncogene expression and histologic parameters were found and comparisons of the mean value of Ha-ras oncogene expression with the parameters examined showed the following: the stellate tumor margin and the larger tumor size had the lowest mean value; the infiltrating duct histologic type had the highest mean value; the mean value was lower in the presence of lymphocytic infiltration in the tumor; a higher mean value was obtained in cases with lymph node metastases.
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PMID:Comparative study of Harvey-ras oncogene expression with conventional clinicopathologic parameters of breast cancer. 241 78

Using in vitro gene amplification by the polymerase chain reaction (PCR) and mutation detection by the RNAase A mismatch cleavage method, we have examined c-K-ras genes in human pancreatic carcinomas. We used frozen tumor specimens and single 5 micron sections from formalin-fixed, paraffin-embedded tumor tissue surgically removed or obtained at autopsy. Twenty-one out of 22 carcinomas of the exocrine pancreas contained c-K-ras genes with mutations at codon 12. In seven cases tested, the mutation was present in both primary tumors and their corresponding metastases. No mutations were detected in normal tissue from the same cancer patients or in five gall bladder carcinomas. We conclude from these results that c-K-ras somatic mutational activation is a critical event in the oncogenesis of most, if not all, human cancers of the exocrine pancreas.
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PMID:Most human carcinomas of the exocrine pancreas contain mutant c-K-ras genes. 245 89

The oncogenes most frequently detected in human tumors belong to the ras gene family (Ha-ras, Ki-ras, and N-ras). These genes encode a group of closely related 21,000 dalton proteins termed p21. An immunohistochemical study of ras p21 expression was carried out on paraffin sections of 54 human breast carcinomas using monoclonal antibodies to p21. The control group consisted of ten cases of benign fibrocystic disease. The p21 expression was significantly higher in cancer cells than in epithelial cells of control specimens. No correlations, however, were observed between oncogene product expression and tumor size, histologic type, or grade. As a group, tumors with axillary lymph node metastases expressed higher levels of ras p21 than nonmetastasizing tumors. However, because of the significant overlap in individual p21 values, it is unlikely that the immunohistochemical assay for p21 could be used to predict the behavior of mammary carcinomas.
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PMID:Expression of ras oncogene p21 protein in relation to regional spread of human breast carcinomas. 246 32

Cell fusion experiments have predicted the existence of cancer metastasis suppressor genes. The E1a gene of Adenovirus 2 has been demonstrated to suppress c-Ha-ras induction of experimental metastatic potential in rat embryo fibroblasts. Another approach to the identification of candidate metastasis suppressor genes has utilized differential or subtraction hybridizations to clone genes which are downregulated as cells become highly metastatic. To date, three such genes have been identified: nm23, WDNM1, and fibronectin. With regard to nm23, downregulation of nm23 RNA levels in high metastatic potential cells has been demonstrated in a wide variety of rodent metastasis systems, including K-1735 murine melanoma cell lines, nitrosomethylurea-induced rat mammary tumors, MMTV-induced mouse mammary tumors, and ras +/- E1a transfected rat embryo fibroblasts. Whether the expression of the nm23 gene, and other down-regulated genes in tumor metastasis, correlates with changes in metastatic potential, or actually has suppressive activity, will require transfection experiments.
Invasion Metastasis 1989
PMID:Search for metastasis suppressor genes. 253 85

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

The in vivo growth behavior and invasive potential of normal and "immortalized" human bronchial epithelial cells were studied by xenotransplantation procedures, an in vitro assay of invasiveness, and determinations of type IV collagenase activity and mRNA expression. BEAS-2B cells, immortalized after hybrid virus infection (adenovirus 12-simian virus 40), reconstituted a columnar epithelium when xenotransplanted into de-epithelialized rat tracheas transplanted sc into athymic BALB/c mice. A few adenomatous growths could be seen 16 weeks after transplantation. BZR cells, obtained by transfer of the v-Ha-ras oncogene into BEAS-2B cells, were tumorigenic in this xenotransplantation model. BZR-T33 cells, obtained from a tumor produced after injection of BZR cells, were also tumorigenic; however, they exhibited a shorter latent period. When these same cell lines were injected sc and iv into athymic BALB/c mice, BEAS-2B cells were not tumorigenic, and the BZR-T33 cells were more tumorigenic than the BZR cells. The incidence of spontaneous metastases after sc inoculation was zero for BEAS-2B cells, 33% for BZR cells, and 100% for BZR-T33 cells. Similar increasing values that correlated well with the data on in vivo growth were noted in the in vitro invasion assay, the collagenolytic ability, and the mRNA expression of type IV collagenase. Normal human bronchial epithelial cells showed the lowest values in all the assays. These progressive changes occurring in cells derived from the same parental line indicate that the presence of the v-Ha-ras oncogene in immortalized bronchial cells is associated with a full-fledged malignant phenotype, which is further enhanced by in vivo passaging.
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PMID:Invasive and metastatic potential of a v-Ha-ras-transformed human bronchial epithelial cell line. 253 88

A patient with two intracerebral glioblastomas of differing histology with metastases to the liver in the absence of surgery is reported. The gliomatous nature of the lesions was confirmed by staining for glial fibrillary acidic protein. Histological and immunohistochemical evidence suggests that the metastases arose from the more poorly differentiated of the intracerebral tumors. One of the intracerebral tumors had enhanced expression of the ras p21 oncogene as compared to the other tumors and as compared to nonmalignant brain tissue from this patient.
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PMID:Multifocal glioblastoma with liver metastases in the absence of surgery. Case report. 255 82

DNAs from 37 human gastric carcinomas and seven lymph node metastases were analyzed for alterations of the epidermal growth factor receptor (EGFR) gene and oncogenes by the Southern blot hybridization method. The probes used were EGFR gene, c-Ha-ras, v-Ki-ras, N-ras, c-myc, v-myb, v-fos, c-erbB-2, v-erbA, v-abl and v-fes. Amplification of the EGFR gene was detected in only one poorly differentiated adenocarcinoma. Amplifications of c-myc gene and c-erbB-2 gene were each observed in two well differentiated adenocarcinomas. One of these tumors had coamplification of c-erbB-2 and c-erbA genes but there were no amplifications nor rearrangements of other oncogenes. The poorly differentiated adenocarcinom with amplified EGFR gene also showed enhanced expression of EGFR gene by Northern blot analysis and additionally had strong synchronous immunoreactivity for EGFR and EGF.
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PMID:Amplification of epidermal growth factor receptor (EGFR) gene and oncogenes in human gastric carcinomas. 257 Apr 89

Aromatic polyamidines containing two, three or four benzamidine residues inhibit proteinase activity and proliferation of different human tumor cell lines, including leukemic (K562, HEL), melanoma (Colo 38) and B-lymphoid (WI-L2) cell lines. In addition, the benzamidine derivatives analysed in the present study inhibit cell growth of the Chinese hamster FHO6T1-1 cell line, obtained after transfection of primary lung cells with the activated human T24-Ha-ras-1 oncogene. After treatment of FHO6T1-1 cells with benzamidine derivatives, a sharp decrease of the content of Ha-ras-1 mRNA was found, but not of transferrin receptor mRNA. We found that inhibition of cell proliferation by tetra-benzamidine derivatives is not restricted to tumor cells, but concerns also non-tumorigenic cell lines as well as normal primary fibroblasts. Therefore, our analysis was extended to di- and tri-benzamidine derivatives, which could be proposed as useful substrates in the synthesis of drug-conjugated monoclonal antibodies or growth factors. The data obtained demonstrate that these latter compounds and their halo-derivatives also exhibit strong antiproliferative effects on in vitro cultured cells.
Clin Exp Metastasis
PMID:Inhibition of 'in vitro' tumor cell growth by aromatic polyamidines exhibiting antiproteinase activity. 264 70


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