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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The growth and metastatic behavior of three human tumor cell lines and a human colon carcinoma previously passaged in vivo were compared between nude mice and scid mice after xenotransplantation. The three human tumor lines included a bladder carcinoma (T24B), a melanoma (RPMI 7931) and a lacZ gene-transduced breast cancer (MDA-MB-435 BAG). The lacZ gene codes for beta-galactosidase, which can be stained blue with chromogenic substrate X-gal, thus allowing the highly sensitive detection and quantitative examination of human cancer metastasis in host mice. Adult (7-14 weeks) NMRI nude and C.B-17 SCID mice were inoculated with 0.5-5 x 10(6) tumor cells s.c. Comparable take rate, latent period and growth rate of implanted tumors were observed in nude and scid mice for each of the cell lines tested. At the time of autopsy, which varied from 6 to 11 weeks after inoculation, a significantly higher incidence of spontaneous lung metastasis was discovered in scid mice (96%) than in age-matched nude mice (27%, total P less than 0.001). In vitro assays for NK cell-mediated cytotoxicity revealed no significant differences between the two strains of mice. Our results suggest that nude and scid mice are equally suitable for propagating human tumors. However, the metastatic capacity of human tumor cells appears to be better expressed in scid mice. Scid mice may therefore provide an advantageous model for the study of human tumor metastasis.
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PMID:Comparative studies between nude and scid mice on the growth and metastatic behavior of xenografted human tumors. 158 90

Previous studies have shown that certain chemotherapeutic drugs are less effective on tumor cells when cells have been previously exposed to hyperthermia. In the present study, we have evaluated whether specific modifications in heat shock protein (hsp) expression are associated with resistance to anticancer drugs. RNA levels for hsp90, hsp70, and hsp27 were studied by Northern and slot blots, while proteins were studied by two-dimensional gel electrophoresis, in MCF-7/BK and MDA-MB-231 breast cancer cells. The sensitivities of these cells to doxorubicin, colchicine, 5-fluorouracil, cisplatin, actinomycin D, and methotrexate were tested by clonogenic assays. These techniques were applied to both cell lines before (control) and after heat shock. The study revealed that elevated hsp70 and hsp27 levels were associated with doxorubicin resistance. In addition, the presence of phosphorylated hsp27 isoforms was also associated with doxorubicin resistance. The study showed that elevated hsps were not associated with multidrug resistance. Heat shock did not induce P170 glycoprotein mRNA overexpression or resistance to the other drugs tested. We also found that the level of doxorubicin protection conferred by the overexpression of hsp was lower than that obtained in cells expressing a multidrug resistance phenotype (MDA-A1R cells). In these cells, heat shock did not confer additional doxorubicin resistance and hsp27 phosphorylation was deficient. Our studies suggest that specific hsps are associated with doxorubicin resistance in certain human breast cancer cells and that this mechanism seems to be independent of the multidrug resistance system.
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PMID:Response of human breast cancer cells to heat shock and chemotherapeutic drugs. 161 38

The influence of various normal and malignant human cells on the level of collagen synthesis by human fibroblasts was tested in coculture. As revealed by immunoperoxidase staining, in cocultures with breast adenocarcinoma cells (MCF7, SA52, T47D) fibroblasts synthesized collagen while tumor cells did not. Fibroblasts displayed increased collagen production without change in the overall protein synthesis. Several other types of cells derived from normal human tissues (keratinocytes, normal mammary cells) or from fibrosarcoma, melanoma, cervical carcinoma, choriocarcinoma, or other breast adenocarcinoma (SW613, MDA, BT20) did not affect collagen synthesis of fibroblasts. Although to a lesser extent, this stimulating effect was reproduced by using the conditioned medium (CM) of the active cells but not with CM of the other cell types. A slight stimulation was also obtained when tumoral MCF7 cells and fibroblasts shared the same medium but were physically separated, suggesting that close contact was required for optimal stimulation of collagen synthesis. The collagen synthesis stimulating activity was not related to a modification of fibroblast proliferation rate. The production of collagen types I, III, and VI and fibronectin were increased in cocultures of fibroblasts with MCF7 cells. The increased synthesis of collagen types I and III and fibronectin was paralleled by similar changes in the steady-state level of their mRNAs. On the contrary, the increased production of collagen type VI appeared regulated at a post-transcriptional level.
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PMID:Modulation of collagen and fibronectin synthesis in fibroblasts by normal and malignant cells. 161 29

We have examined the distribution of phospholipase C-gamma 1 (PLC-gamma 1) between membrane and cytosolic fractions in several cell lines. In MDA-468 cells, which are derived from a human breast tumor, greater than one-half of the total PLC-gamma 1 is associated with the membrane fraction of the cell. Unlike the situation in A-431 cells [G. Todderud, M. I. Wahl, S. G. Ree, and G. Carpenter, Science, 248: 296-298, 1990], epidermal growth factor (EGF) stimulation of MDA-468 cells does not result in significantly increased PLC-gamma 1 association with membranes. Immunoblot analysis reveals low levels of phosphotyrosine in PLC-gamma 1 and EGF receptors in unstimulated MDA-468 cells and greatly increased phosphotyrosine levels in these proteins as a result of EGF stimulation of the cells. We conclude that autocrine activation of EGF receptors is not responsible for the elevated association of PLC-gamma 1 with membranes in these cells.
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PMID:Elevated membrane association of phospholipase C-gamma 1 in MDA-468 mammary tumor cells. 164 44

B1 and B3 are two newly isolated monoclonal antibodies that react uniformly with the surface of many mucinous carcinomas of the colon, stomach, and ovary but with a limited number of normal tissues, among which are glands of the stomach, epithelia of the trachea and bladder, differentiated epithelium of the esophagus, and small bowel mucin. They also react uniformly with many human tumor cell lines, including MCF7, MDA-MB-468, and HTB20 (breast), A431 (epidermoid), HT29 (colon), HTB33 (cervical), and DU145 (prostate). Immunoprecipitation experiments indicate that B1 and B3 react with epitopes present on a large number of glycoproteins, ranging in molecular weight from greater than 200,000 to less than 40,000. Using a panel of 37 different carbohydrate residues attached to albumin to form neoglycoproteins, it was found that B1 reacts with Ley and H-type 2 and B3 reacts with Ley, di-Lex, and tri-Lex antigens. Thus, each antibody reacts with a distinct portion of a carbohydrate residue. Because of the limited reactivity of these antibodies with normal tissues, they merit evaluation in the treatment of cancer.
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PMID:Characterization of monoclonal antibodies B1 and B3 that react with mucinous adenocarcinomas. 164 44

In response to a given stimulus, usually a number of cytokines are secreted simultaneously by the immune system. Whether these cytokines are meant to function as a single agent or in combination with others is not understood. Tumor necrosis factor (TNF) has been shown to exhibit antiproliferative effects against a wide variety of tumor cell lines in vitro. In the present report, we investigated the effects of a T-cell-derived cytokine, interleukin 4 (IL-4), on the antiproliferative effects of TNF against different tumor cell lines. The growth characteristics of human breast cancer cells (MDA-MB-330) were minimally affected when the cells were exposed to either TNF or IL-4 alone. However, together these 2 cytokines inhibited cell growth in a dose-dependent manner. The enhancement of the cytotoxic effects of TNF by IL-4 were not just limited to breast tumor cells, but were also observed with human epidermoid carcinoma cells (A-431) and human histiocytic lymphoma cells (U-937). The enhancement of the cytotoxic effect of TNF by IL-4 against various tumor cell lines was found comparable with that by gamma-interferon (IFN-gamma). Interestingly, for certain tumor cell types, IL-4 alone was found to enhance cell proliferation. IL-4 had no effect on the growth-stimulatory activity of TNF on normal human foreskin fibroblasts. Pre-exposure of U-937 cells to IFN-gamma led to a greater than 2-fold induction in TNF receptors, but no modulation of TNF receptors by IL-4 was observed. Moreover, the presence of IFN-gamma was found to further potentiate the antiproliferative effects of TNF and IL-4. These results clearly suggest that IL-4 potentiates the antiproliferative responses of TNF by a mechanism different from that of IFN-gamma. Although it is well known that IL-4 can modulate the production of TNF from macrophages, this is the first report to suggest that IL-4 can also modulate TNF-dependent antiproliferative responses.
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PMID:Interleukin 4 potentiates the antiproliferative effects of tumor necrosis factor on various tumor cell lines. 165 Nov 57

Previous studies have shown several similarities between an estrogen-regulated heat shock protein of 24,000-28,000 daltons (hsp27), and a cytoplasmic estrogen receptor-associated protein of 27,000-29,000 daltons (p29). These proteins have been studied by monoclonal antibodies generated in different laboratories. In the present report we have performed immunocytochemical and immunoblot studies to explore if the monoclonal antibodies against hsp27 (C11) and against p29 (ER-D5) may be identifying the same protein. Breast and endometrial carcinomas and normal endometrial samples were examined by immunocytochemistry (in mirror sections and by double-immunostaining). Identical hsp27 and p29 immunostaining intensity, distribution, and percentage of stained cells was demonstrated by immunocytochemistry. The antigens examined by the two antibodies appeared in the same cells. Cytosols from tumors analyzed by the Western blot technique revealed that the C11 and the ER-D5 antibodies recognized bands with identical electrophoretic mobility. Immunoprecipitation studies with one antibody, C11, followed by Western blot showed that the precipitate was reactive with both antibodies. Identical C11 and ER-D5 reacting spots were observed after blotting proteins separated by high resolution two-dimensional gel electrophoresis. In addition, p29 protein was induced by heat shock in the estrogen receptor negative MDA-MB-231 human breast tumor cell line. These results strongly suggest that the two proteins under investigation are identical.
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PMID:Immunological evidence for the identity between the hsp27 estrogen-regulated heat shock protein and the p29 estrogen receptor-associated protein in breast and endometrial cancer. 166 87

An antigen, immunologically related to the external domain of the c-erbB-2 (HER-2/neu) protein, was found shed into the serum of nude mice bearing tumors that overexpress the c-erbB-2 protein (gp185). Utilizing paired combinations from a panel of monoclonal antibodies (TAbs 250-265), with specificity for extracellular epitopes of gp185, an immunoradiometric assay was developed to quantitate this shed antigen. The immunoradiometric assay detected membrane-bound and soluble gp185 as well as a soluble derivative corresponding in sequence to the extracellular domain of gp185 (designated gp75). This recombinantly expressed gp75 was immunoaffinity purified and used to generate a standard curve from which serum samples were quantitated. Increases in antigen levels measured in the sera of tumor-bearing nude mice correlated with both overexpression of the c-erbB-2 protein and increased tumor volume. Positive sera were obtained from mice given implants of NIH3T3 cells transfected with c-erbB-2 complementary DNA (NIH3T3t), or ovarian (SK-OV-3) or breast (MDA-MB-361) tumor cell lines overexpressing the c-erbB-2 protein. In mice bearing NIH3T3t tumors, increases in tumor volume from 80 to 9000 mm3 resulted in levels of shed antigen from 8 to greater than 1000 ng/ml gp75 equivalents. Sera from mice with c-erbB-2-negative tumors or tumors overexpressing the epidermal growth factor receptor were negative in the assay. This assay, and the quantitation of shed antigen levels, may have diagnostic or monitoring utility in cancers, such as breast and ovarian, in which the c-erbB-2 protein is overexpressed.
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PMID:An antigen immunologically related to the external domain of gp185 is shed from nude mouse tumors overexpressing the c-erbB-2 (HER-2/neu) oncogene. 167 37

A rapid, simple and non-toxic procedure for the simultaneous isolation of DNA and RNA from tumor tissue and cells grown in vitro is described. Guanidinium isothiocyanate was used for homogenization of tumor tissue and for cell lysis. Separation of proteins, DNA and RNA was carried out by isopycnic centrifugation in cesium trifluoroacetate. DNA was further purified by salting out residual protein. Nucleic acids prepared by this method from 47 primary human carcinomas and 17 human cell lines were analysed for amplification and expression of the HER-2/neu proto-oncogene. 2- to 10-fold amplification of HER-2/neu was noted in 7/22 mammary carcinomas (32%) and in 4/14 ovarian carcinomas (28%). No amplification of the proto-oncogene was found in 4 laryngeal carcinomas, 1 pharyngeal carcinoma, 2 retrolingual carcinomas, 3 gastric carcinomas and 1 kidney carcinoma. HER-2/neu overexpression was observed in 6/22 of mammary carcinomas (27%) and 7/14 of ovarian carcinomas (50%). No overexpression was found in all other carcinomas studied. Concordance between amplification and overexpression was noted in 3 mammary and 4 ovarian carcinomas, respectively. 3 mammary and 3 ovarian carcinomas showed overexpression without amplification. 5 human mammary carcinoma cell lines showed both amplification and overexpression of HER-2/neu. In two mammary carcinoma cell lines (MDA MB-453 and ZR 75-1) overexpression was noted without amplification of the proto-oncogene. These data combine to suggest that mechanisms other than gene amplification may also lead to overexpression of the HER-2/neu protooncogene in cancer cells.
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PMID:Determination of HER-2/neu amplification and expression in tumor tissue and cultured cells using a simple, phenol free method for nucleic acid isolation. 169 98

Breast tumor cell lines have been shown to secrete several distinct polypeptide growth factors, although conflicting results exist for the insulin-like growth factors (IGFs). In contrast a limited number of breast tumor cell lines have definitely been shown to secrete the high affinity IGF binding proteins (IGFBPs) that modify IGF actions. To characterize the types of IGFBPs that are secreted by breast tumor cell lines, conditioned medium was collected from seven separate tumor cell lines, three of which were estrogen receptor (ER) negative, and four of which were ER positive. All three of the ER negative cell lines, MDA-231, MDA-330, and HS578T, secreted binding proteins of 49,000 and 43,000 Mr (IGFBP-3) as well as 29,000 (IGFBP-1) and 24,000 Mr. In contrast, all four ER positive cell lines secreted 34,000 (IGFBP-2) or 24,000 Mr forms, and none secreted the 49,000 and 43,000 or 29,000 Mr forms. BT-20, a cell line that is positive for ER messenger RNA (mRNA) but negative for ER protein, secreted predominantly a 34,000 Mr protein. The amount of total IGFBP activity released in 24 h ranged between 0.4 and 5.6 nM equivalents of IGFBP-1, and there was no significant difference between the ER positive and negative cell lines. The MCF-7 cells that produced predominantly 34,000 and 24,000 Mr forms showed a 1.8-fold increase in IGFBP secretion after estrogen stimulation. Immunoblotting and a specific RIA for IGFBP-1 showed that only the ER negative lines MDA-330, MDA-231, and HS578T secreted this form. Northern blotting analysis for the mRNA encoding this protein showed that both MDA-330 and MDA-231 contained a single 1.6 kilobase mRNA species that hybridized with an IGFBP-1 complementary DNA (cDNA) probe. Immunoblotting analysis of the other cell lines showed that only the 34,000 Mr form secreted by the ER positive cell lines reacted with IGFBP-2 antisera. Exposure of the conditioned media from the three ER negative cell lines to N-glycanase revealed that the 49,000 and 43,000 Mr forms of IGFBP were glycosylated and therefore probably represent IGFBP-3. We conclude that ER negative cell lines secrete three forms of IGFBPs, IGFBP-1, IGFBP-3, and a 24,000 Mr form. In contrast, the ER positive cell lines secrete predominantly IGFBP-2 and the 24,000 Mr form but do not secrete IGFBP-3 or 1.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Insulin-like growth factor binding protein secretion by breast carcinoma cell lines: correlation with estrogen receptor status. 170 Nov 24


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