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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have previously demonstrated that second-passage rat embryo cells transformed by the ras oncogene alone are both tumorigenic and highly metastatic when injected into nude mice. In contrast, rat embryo cells cotransformed with the ras oncogene and the adenovirus type 2 (Ad2) E1a gene are tumorigenic but either fail to metastasize or exhibit a very low metastatic potential. In this report, we demonstrate that transfection of the Ad2 E1a gene into four independent ras-transformed rat embryo cell lines results in a dramatic reduction in metastatic potential relative to that of the parental cell line. Transfection of cDNAs for the 12S and 13S E1a transcripts showed that the 12S cDNA was highly effective in reducing the metastatic potential of ras-transformed cell lines, while the 13S cDNA showed an effect in only one of the two cell lines tested. This effect is specific to the Ad2 E1a gene, since ras-transformed cell lines expressing the Ad12 E1a gene maintained their high metastatic potential. We hypothesize that the Ad2 E1a gene may regulate the expression of one or more cellular genes that contribute to the metastatic phenotype.
Mol Cell Biol 1988 Jul
PMID:The E1a gene of adenovirus type 2 reduces the metastatic potential of ras-transformed rat embryo cells. 297 8

Transplantation of five liver tumors induced with the chemicals diethylnitrosamine (DEN) and 7,12-dimethylbenz[a]anthracene (DMBA) in small live-bearing fish of the genus Poeciliopsis is reported. Five permanent strains representing three distinct tumor types were established in isogenic hosts. Histological characterization of hepatocellular carcinoma, hemangiopericytic sarcoma, and cholangiocarcinoma and the development of the neoplasms in host fish is presented. Transplantability of the experimental liver tumors provides evidence of their malignant nature. Metastasis of the hepatocellular carcinoma occurred from tumor implants in the dorsal musculature or peritoneal cavity and from the hemangiopericytic sarcoma implanted in the intraperitoneal cavity.
Exp Mol Pathol 1985 Jun
PMID:Transplantable chemically-induced liver tumors in the viviparous fish Poeciliopsis. 298 24

Activated ras oncogene transfection into suitable recipient cells has been shown to induce the metastatic phenotype (Thorgeirsson, et al., Mol. Cell. Biol., 5: 259-262, 1985). We have used this model system to study the correlation of basement membrane collagenolysis with metastatic propensity. The c-Ha-ras oncogene alone, or combined with v-myc, transfected into early passage rat embryo fibroblasts, induce these cells to secrete high levels of type IV collagenolytic metalloproteinase and to concomitantly exhibit a high incidence of spontaneous metastases in nude mice. Cotransfection of c-Ha-ras plus the adenovirus type 2 E1a gene yields cells which are highly tumorigenic but nonmetastatic and fail to produce type IV collagenase. This effect is due to a suppression of collagenase elaboration, not increased production of a collagenase inhibitor, and not decreased production of a collagenase activator. The characteristics of the collagenase are identical to tumor type IV collagenase described previously. The nonmetastatic cells which failed to produce type IV collagenase retain the ability to secrete high levels of plasminogen activator. Transfection with the protooncogenic forms of Ha-ras or mos, or spontaneous transformation of NIH 3T3 cells or chemical transformation of BALB 3T3 cells yields cells which fail to produce collagenase, are tumorigenic, but totally nonmetastatic. These data support a biochemical linkage of type IV collagenase expression with the metastatic phenotype in this rodent system.
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PMID:Secretion of type IV collagenolytic protease and metastatic phenotype: induction by transfection with c-Ha-ras but not c-Ha-ras plus Ad2-E1a. 302 10

Retrovirus vector infection was used to introduce large numbers of unique genetic markers into tumor cell populations for the purpose of analyzing comparative changes in the clonal composition of metastatic versus that of nonmetastatic tumors during their progressive growth in vivo. The cell lines used were SP1, a nonmetastatic, aneuploid mouse mammary adenocarcinoma, and SP1HU9L, a metastatic variant of SP1. Cells were infected with delta e delta pMoTN, a replication-defective retrovirus vector which possesses the dominant selectable neo gene and crippled long terminal repeats. G418r colonies were obtained at a frequency of 4 x 10(-3). Southern blot analysis of a number of clones provided evidence of random and heritable integration of one or two copies of the proviral DNA. Clonal evolution of primary tumor growth and the nature of lineage relationships among spontaneous metastases and primary tumors were analyzed by subcutaneously injecting 10(5) cells from a pooled mixture of 3.6 x 10(2) G418r SP1HU9L or 10(4) G418r SP1 colonies into syngeneic CBA/J mice. The most striking finding was the relative clonal homogeneity of advanced primary tumors; they invariably consisted of a small number (less than 10) of distinct clones despite the fact that hundreds or thousands of uniquely marked clones had been injected. In the case of the metastatic SP1HU9L cells, the nature of these "dominant" clones varied from one tumor to another. Analysis of a number of lung metastases revealed that a proportion of them were derived from dominant primary tumor clones and were composed of one, and sometimes two, distinct progenitors. In some animals, all the lung metastases were derived from a common progenitor clone, whereas in others, each metastatic nodule had a different progenitor. The results show the following. (i) Retrovirus vector infection can be used to introduce large numbers of unique and stable clonal markers into tumor cell populations. (ii) The progeny of a very limited number of clones dominate in advanced primary tumors. (iii) Mammary carcinoma metastases are of mono- or biclonal origin. The significance of the results is discussed.
Mol Cell Biol 1988 Aug
PMID:Genetic tagging of tumor cells with retrovirus vectors: clonal analysis of tumor growth and metastasis in vivo. 321 Nov 40

The vascular bed of the lung is susceptible to environmental and host-mediated injury from free radicals. The lung is also a frequent site for the formation of cancer metastases. Since the circulation is important for the spread of cancer and because the endothelium is a barrier between the circulation and extravascular tissue, we have postulated that free radical damage to the pulmonary microvasculature enhances the formation of metastases. Pulmonary endothelial injury was induced in mice by bleomycin (120 mg/kg i.v.) or by exposure to 90% oxygen for 2-4 days. In rats, damage was elicited by intravenous injection of cobra venom factor which activates the circulating leukocytes. Endothelial damage was demonstrated by morphology and by measurement, in lung lavage fluids, of increased protein and/or leakage of 125I-albumin, previously injected intravenously. When radiolabeled cancer cells were injected into the tail vein during periods of pulmonary endothelial damage, there was a 3-36 fold increase in the numbers of these cells located in the lung after 24 hours. Subsequently more metastatic tumors formed in the animals with injured lungs. In rats, the enhanced localization was prevented by pretreatment of the animals with catalase or with antineutrophil antibodies. We have also demonstrated that stimulation of rat cancer cells by the chemotactic peptide N-fMLP is followed by chemiluminescence, amplified in the presence of luminol. Evidence for the generation of oxygen radicals by these cells includes inhibition of the response in the absence of oxygen or in the presence of superoxide dismutase, catalase, and mannitol, and dose-dependent reduction of acetylated cytochrome C. We conclude that free radical-mediated damage to the pulmonary endothelium significantly increases the metastasis of circulating tumor cells and we postulate that some cancer cells may directly facilitate their spread by generating free radicals.
Mol Cell Biochem 1988 Dec
PMID:The effects of oxygen radical--mediated pulmonary endothelial damage on cancer metastasis. 323 Dec 22

Following preliminary studies suggesting that some patients with metastatic renal cell carcinoma had accelerated tumor growth after entry into chemotherapy studies, 73 patients with measurable metastatic disease referred to a tertiary referral center for consideration for experimental treatment protocol have been observed to attempt to establish the incidence of spontaneous regression. Initially, patients went off study if metastases showed greater than 25% increase in products of bidimensional measurement but with increasing confidence patients only went into therapy protocols with the development of symptomatic progression. In this selective series, on observation, three complete (histologically documented) and two partial unexplained "spontaneous" regressions were observed and a further four patients had prolonged stable disease for more than 12 months. On progression, 52 were entered into treatment protocols (BCG n = 19, Mitozantrone n = 12, and Welferon n = 21). A further two complete and five partial responses (14%) and four prolonged stable disease were observed confirming that the previously reported responses with these agents are not totally explicable on the basis of "spontaneous" response.
Mol Biother 1988
PMID:A phase 2 study of surveillance in patients with metastatic renal cell carcinoma and assessment of response of such patients to therapy on progression. 326 68

This study was carried out to assess the utility of antibodies raised to synthetic peptides of the predicted sequence of the c-erbB-2 gene product to identify immunocytochemically those tumours overexpressing this putative transmembrane receptor. Staining with rabbit antiserum 21N gave the best correlation with gene amplification and did not stain the membrane of any of the normal tissues at the dilution which strongly stained the membrane of any of the normal tissues at the dilution which strongly stained the amplified tumours. No significant correlation was found with lymph node involvement, epidermal growth factor receptor status or with oestrogen receptor levels. Of the 12 out of 34 cases which demonstrated c-erbB-2 gene amplification in the primary tumour, two had lymph node metastases which were also positive immunocytochemically. Fourteen other cases which had lymph node metastases were negative in the primary tumour and in the metastases. These tumours all showed strong membrane positivity. A comparison of modified methacarn and formol saline fixation demonstrated an increased sensitivity with the former, but the staining pattern was unaltered. This small but extensively studied group of cases has indicated that increased c-erbB-2 protein can be identified routinely in fixed tissue sections, making it possible to carry out extensive studies to look for clinical correlates, but also to assess the stage in tumour progression at which the increased expression occurs and whether it correlates with any potentially premalignant condition.
Mol Cell Probes 1987 Dec
PMID:Immunohistochemical localization of c-erbB-2 in human breast carcinomas. 333 Sep 98

Expression of the calcitonin (CT)/calcitonin gene related peptide (CGRP) gene and the proopiomelanocortin (POMC) gene has been demonstrated by Northern blot hybridization analysis of RNA extracted from human medullary thyroid carcinoma (MTC), pheochromocytoma and lung carcinoma. CT mRNA in these tumors could not be distinguished in size from CT mRNA isolated from normal human thyroid tissue. CGRP mRNA (previously demonstrated in 12 out of 12 lung tumor cell lines investigated) could not be detected in 13 primary lung tumors or 10 metastases thereof. The length of POMC mRNA in MTCs (present in all 4 metastases investigated but not in 7 primary tumors) and pheochromocytomas is about 100 nucleotides more than pituitary POMC RNA. In lung tumors 2 POMC RNA species can be detected, one of the same size as in pituitary tissue and one about 100 nucleotides larger.
Mol Cell Endocrinol 1986 Sep
PMID:Detection of mRNA encoding calcitonin, calcitonin gene related peptide and proopiomelanocortin in human tumors. 348 30

The analysis of 11 various oncogenes expression in different human tumors showed that each tumor is characterised by a specific functioning program of these genes. In 40-50% of tumors the oncogenes ras, fos and myc are expressed. All other oncogenes are either considered to be "silent" or are expressed only in few cases. The increased expression of sis and myb oncogenes is observed in metastases.
Mol Biol (Mosk)
PMID:[Transcription of cellular oncogenes in human tumors]. 377 91

To investigate a role for surface carbohydrates in cellular malignancy, 15 different glycosylation-defective CHO cell mutants were examined for their tumorigenic and metastatic capacities after subcutaneous injection into nude mice. Most of the glycosylation mutants displayed similar or slightly decreased tumorigenicity compared with parental CHO cells. Neither parental CHO cells nor any of the mutants were observed to metastasize. However, independent isolates of one mutant type, Lec9, showed a dramatic reduction in tumor formation. The altered carbohydrates expressed at the surface of Lec9 cells appeared to be responsible for their loss of tumorigenicity, because revertants for lectin resistance were able to form tumors, and a double mutant (Lec9.Lec1) that expressed a Lec1 glycosylation phenotype also formed tumors. Finally, Lec9 cells were able to form tumors in gamma-irradiated nude mice, suggesting that recognition by an irradiation-sensitive host cell(s) was responsible for their reduced tumorigenicity in untreated nude mice.
Mol Cell Biol 1986 Apr
PMID:Decreased tumorigenicity correlates with expression of altered cell surface carbohydrates in Lec9 CHO cells. 378 64


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