Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0007097 (carcinoma)
 152,788 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Although 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] has been shown to inhibit the growth of certain malignant cells, its hypercalcemic effect has prevented clinical application. We have recently developed a novel vitamin D3 analog, 22-oxa-1,25-(OH)2D3 (OCT), that is capable of promoting differentiation and inhibiting proliferation without inducing hypercalcemia. The present study was undertaken to determine whether OCT could be applied for the treatment of breast cancer with or without estrogen receptor (ER). OCT inhibited the proliferation of both ER-positive (MCF-7, T-47D, and ZR-75-1) and ER-negative breast cancer cells (MDA-MB-231 and BT-20) in vitro in a time- and dose-dependent manner, as determined by cell number and [3H]thymidine uptake. The antiproliferative effect was observed with a concentration as low as 10(-11) M OCT, and treatment of MCF-7 cells with 10(-8) M OCT for 8 days caused more than a 50% reduction in cell number compared with that of vehicle-treated cells. OCT was approximately 1 order of magnitude more potent than 1,25-(OH)2D3 in inhibiting the proliferation of MCF-7 cells. The in vivo effect of OCT was examined in athymic mice implanted with ER-negative MX-1 tumor, which was established as the xenograft derived from human breast carcinoma. Intratumor administration of OCT three times a week remarkably delayed the growth of MX-1 tumor in a time- and dose-dependent manner. The antitumor effect of 1 microgram/kg BW OCT was greater than that of 500 microgram/kg BW adriamycin, and the relative tumor weights in each group on day 26 were 29.7% and 50.5% of that in the vehicle-treated group, respectively. The effects of OCT and adriamycin were additive, and the relative tumor weight after 26 days of combined treatment was 21.7% of that in the vehicle-treated group. Oral administration of OCT was also effective, and the relative tumor weight in the OCT-treated group (1 microgram/kg BW) was 54.6 +/- 0.1% (mean +/- SEM) of that in the vehicle-treated group. Neither intratumor nor oral administration of OCT raised the serum calcium level in these animals. These results demonstrate that OCT is a potent inhibitor of the proliferation of breast cancer cells with or without ER and that OCT inhibits the growth of breast cancer in vivo without inducing hypercalcemia. We suggest that OCT may provide a new strategy for the treatment of breast carcinoma regardless of ER status.
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PMID:A novel vitamin D3 analog, 22-oxa-1,25-dihydroxyvitamin D3, inhibits the growth of human breast cancer in vitro and in vivo without causing hypercalcemia. 185 78

The effect of isoflavones on the growth of the human breast carcinoma cell lines, MDA-468 (estrogen receptor negative), and MCF-7 and MCF-7-D-40 (estrogen receptor positive), has been examined. Genistein is a potent inhibitor of the growth of each cell line (IC50 values from 6.5 to 12.0 micrograms/ml), whereas biochanin A and daidzein are weaker growth inhibitors (IC50 values from 20 to 34 micrograms/ml). The isoflavone beta-glucosides, genistin and daidzin, have little effect on growth (IC50 values greater than 100 micrograms/ml). The presence of the estrogen receptor is not required for the isoflavones to inhibit tumor cell growth (MDA-468 vs MCF-7 cells). In addition, the effects of genistein and biochanin A are not attenuated by overexpression of the multi-drug resistance gene product (MCF-7-D40 vs MCF-7 cells).
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PMID:Genistein inhibition of the growth of human breast cancer cells: independence from estrogen receptors and the multi-drug resistance gene. 188 87

A series of isomeric [1,2-bis(difluorophenyl) ethylenediamine]dichloroplatinum(II) complexes and cisplatin were tested on the P388 leukemia and on the murine hormone-independent MXT (M3.2) OVEX and the ovarian-hormone-dependent MXT (M3.2) mammary carcinoma for evaluating antineoplastic activity against breast cancer in vivo. Although these results were heterogeneous, a trend to the 2,6-difluorosubstituted compound as the most active platinum complex was observed. For the development of a large-scale in vitro screening method on human breast cancer cell lines, cell number, [3H]thymidine incorporation, and crystal violet staining were evaluated as parameters for end-point determination. Chemosensitivity testing on the human breast cancer cell lines MDA-MB-231 and MCF-7 unambiguously identified [1,2-bis(2,4-difluorophenyl)ethylenediamine]dichloroplatinum(II) as the complex with the highest activity in the crystal violet micro-assay. In equimolar concentration this compound was superior to cisplatin on both cell lines. The analysis of the conflicting results of this study indicates that murine mammary carcinomas are most probably unrealistic and inappropriate models for the screening of cytotoxic platinum complexes with potential activity on human breast cancer.
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PMID:Different response of murine and human mammary tumour models to a series of diastereoisomeric [1,2-bis(difluorophenyl) ethylenediamine]dichloroplatinum(II) complexes. 189 Jan 39

Interferons (IFNs) may inhibit cell growth via their interaction with growth factors and their receptors. We examined the ability of IFN to modulate Epidermal Growth Factor (EGF) receptor binding in a human breast carcinoma cell line, MDA 468. Gamma interferon and alpha interferon inhibited growth of MDA 468 cells in a dose and time-dependent manner. IFN-gamma and Epidermal Growth Factor (EGF), a known inhibitor of MDA 468 growth, inhibited growth in an additive fashion. Growth inhibition by gamma but not alpha interferon was associated with a decrease in the number of EGF receptors (EGFRs) after 5 days. Scatchard analysis of receptor binding data revealed that gamma but not alpha interferon reduced the number of available EGF receptor binding sites without any change in the affinity of the receptor. IFN significantly affected EGF receptor expression, and the decrease in receptor expression was associated with growth inhibition.
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PMID:Modulation of epidermal growth factor receptors by gamma interferon in a breast cancer cell line. 190 74

The interferons are a group of naturally occurring proteins that inhibit the growth of tumours in vivo and many transformed cell lines in vitro. The mechanisms of action of interferon, however, remain unclear. The IFN induced inhibition of growth of many epithelial cancer cell lines is associated with changes in Epidermal Growth Factor Receptor (EGFR) binding or expression. Therefore, we examined the effect of IFN treatment on the expression of EGFR in a human breast carcinoma cell line, MDA 468. We have found the IFN-gamma inhibited, in a dose dependent fashion, the growth of MDA 468 cells. IFN decreased cell surface binding of 125I-EGF to EGFR by changing receptor number rather than affinity. However, total cellular receptor protein, as measured by immunoprecipitation with monoclonal antibodies, was increased in IFN-treated cells. The half-life of the metabolically labelled receptor was unchanged by treatment with IFN. Increased amounts of EGFR mRNA were observed in MDA 468 cells treated with IFN-gamma for 3 days. The levels of mRNA increased with time in culture, reaching a peak of four times control values after 5 days of treatment. This effect was observable with as little as 10 U ml-1 of IFN-gamma. Treatment of the cells with Actinomycin D to inhibit new RNA synthesis suggested that the stability of EGFR mRNA was not enhanced in IFN-gamma treated cells. The increase in receptor mRNA induced by IFN was not inhibited by cycloheximide. These data suggest IFN-gamma can increase expression of EGFR mRNA and protein in MDA 468 cells. Increased expression of EGFR mRNA and protein by IFN-gamma is associated with inhibition of cell growth.
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PMID:Increased epidermal growth factor receptor gene expression by gamma-interferon in a human breast carcinoma cell line. 190 27

The presence of gonadotropin-releasing hormone (GnRH)-binding sites in human breast carcinomas and breast tumor cell lines as well as the demonstration of the inhibitory effects of GnRH analogues on the growth of these cells raised the possibility that GnRH is produced locally by breast tumor cells themselves. Immunoreactive GnRH was shown to be present in acetic acid extracts of cultured MDA-MB-231 and ZR-75-1 breast carcinoma cells. These extracts were separated by high-performance liquid chromatography and were analyzed by means of region-specific antisera with differing GnRH sequence specificities. A peak of GnRH which coeluted with synthetic mammalian GnRH in 2 different high-performance liquid chromatography systems was similarly detected by antisera directed at the NH2 terminus, at the middle portion and at the N and COOH termini together. The GnRH gene is expressed in these breast tumor lines, as determined by S1 nuclease protection assay, oligonucleotide primer extension studies, and polymerase chain reaction amplification of complementary DNA using oligonucleotides. The primer extension studies indicate that several forms of mRNA are present. The predominant form corresponds to the excision of intron I and the use of a start site about 60 bases upstream of intron I as in the human hypothalamus. Less usage is made of other start sites further upstream. Much larger species of mRNA were also present and correspond to the retention of intron I as in human placenta. The demonstration of GnRH gene expression and the presence of immunoreactive GnRH in mammary carcinoma cells known to have GnRH-binding sites and to be affected by GnRH analogues suggests that GnRH may serve an autocrine regulatory role.
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PMID:Gonadotropin-releasing hormone gene expression in MDA-MB-231 and ZR-75-1 breast carcinoma cell lines. 202 39

Human breast carcinoma cell lines MCF-7 and MDA-MB231 were transplanted s.c. to female athymic nude mice at 3-4 weeks of age. At 7-10 days after transplantation, the mice were divided into groups and fed for 6-8 weeks one of the following semi-purified diets containing different amounts and types of fat, i.e. 5% corn oil, 20% corn oil, 20% butter, 19% beef tallow/1% corn oil and 19% fish (Menhaden) oil/1% corn oil. In addition experiments, the fish oil diets were supplemented with antioxidants (vitamin E, 8 g or 2000 IU/kg diet plus tertiary butyl hydroquinone, TBHQ, 4 g/kg diet) or ferric citrate (3 g/kg diet). Tumor peroxidation product levels were assessed by measuring 2-thiobarbituric acid reactants (TBA assay). At the termination of the studies (6-8 weeks of diet feeding) mean human breast carcinoma volume (MCF-7 and MDA-MB231) was the largest in mice fed the 20% corn oil diet, intermediate in mice fed the butter or beef tallow diets and the least in mice fed the fish oil diet. The difference in mean tumor volumes among mice fed the 20% corn oil diet and those fed the fish oil diet was significant (P less than 0.01). When comparing low (5% corn oil) and high (20% corn oil) fat diets, numerical increases in human breast carcinoma volume (MCF-7 and MDA-MB231) were consistently observed in the high-fat diet groups but these differences were not always significant. Tumor lipid peroxidation product levels were determined on the MDA-MB231 tumors; tumor lipid peroxidation levels were significantly (P less than 0.01) increased only in mice fed the fish oil diets. Supplementation of the fish oil diets with antioxidants (vitamin E + TBHQ) significantly reduced the level of tumor peroxidation products and significantly increased tumor volume (P less than 0.05). When tumor lipid peroxidation product levels in the fish oil plus antioxidant fed mice were reduced to the level of that observed in the tumors of the corn oil fed mice, no significant differences in tumor volumes were observed in these two groups. In contrast, supplementation of the fish oil diets with ferric citrate, significantly (P less than 0.05) increased tumor lipid peroxidation product levels and decreased tumor volume. Thus, the type of dietary fat can clearly affect the growth of human breast carcinomas (MCF-7 and MDA-MB231) maintained in athymic nude mice.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Effect of dietary fat on growth of MCF-7 and MDA-MB231 human breast carcinomas in athymic nude mice: relationship between carcinoma growth and lipid peroxidation product levels. 207 Apr 88

Fifteen to 20% of breast carcinomas show amplification of genes located at 11q13. The HST/FGFK and INT2 fibroblast growth factor (FGF)-related genes and the BCL1 locus are usually present in the amplification units. We have investigated the structure and chromosomal location of the 11q13 amplicon of the MDA-MB-134 mammary carcinoma cell line by using in situ chromosomal and pulsed field gel hybridizations. The results indicate that a limited number of amplification units are involved in the constitution of an extended chromosomal region located on 11q. These units do not show any important rearrangement over rather large distances around the HST/INT2 and BCL1 loci.
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PMID:The 11q13 amplicon of a mammary carcinoma cell line. 207 7

The spontaneous expression of HLA class-I and class-II molecules in 5 human breast carcinoma cell lines, MCF-7, T47D, ZR75-1, HSL-53, MDA-MB 231, and their modulation during IFN-gamma treatment, are reported. The expression of cell-surface determinants was examined by indirect immunofluorescence using monoclonal antibodies (MAbs) specific for HLA class-I and class-II (DR, DQ and DP) antigens. The biosynthesis and maturation of these molecules were analyzed by 2-dimensional gel electrophoresis analysis (2D-PAGE) of class I, DR alpha, beta and invariant immunoprecipitates. Transcription was analyzed by Northern blot hybridization with HLA class-I and -II cDNA-specific probes. In all cell lines, more than 80% of cells expressed HLA class-I antigens at their surface. 2D-PAGE and mRNA studies showed a variable basal level of HLA class-I biosynthesis and transcription with a constant increase after 1,000 U/ml IFN-gamma treatment. HLA class-II determinants were totally absent from the surface of MCF-7, MDA MB231, ZR75-1 and T47D but they were detected in a small subpopulation of HSL-53 cells (DR 6%, DQ 6%, DP 20%). Spontaneous biosynthesis of HLA-DR molecules in immunoprecipitates analyzed by 2D-PAGE or transcripts in Northern blot were not detected in the 5 cell lines. Treatment with 1000 U/ml IFN-gamma induced or increased the expression of HLA class-II molecules in all cell lines but DQ expression was variable. While T47D, ZR75-1 and HSL-53 increased their transcripts and antigen expression, MDA, MB231 and MCF-7 showed no DQ mRNA transcript. Biochemical analysis of the DR products revealed a classical alpha, beta and invariant (li) chain pattern, but indicated a constant glycosylation defect in the invariant chain in all cell lines, associated with weak expression of the beta chain and the presence of an extra spot of low molecular weight in the acidic part of the gel. Thus, post-transcriptional events did not appear to be totally controlled by IFN-gamma in the different cell lines. These differences in DQ expression and glycosylation process in different breast cancer cells may be important in the activation of the immune response among different individuals.
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PMID:Effect of gamma interferon on HLA class-I and -II transcription and protein expression in human breast adenocarcinoma cell lines. 211 15

Tumor metastasis requires highly motile cells that can respond to appropriate stimuli. A2058 human melanoma cells were shown previously to secrete a highly potent autocrine motility factor (AMF) that stimulates chemokinetic movement. We have shown that the insulin polypeptides (IPs; insulin-like growth factors I and II [IGF-I, -II] and insulin) stimulated A2058 cell chemotaxis and chemokinesis. We now report that the IPs and AMF stimulate locomotion in other human malignant cell lines. Insulin (100 nM) induced motility of up to 50% of the magnitude of the AMF response in human carcinoma lines MDA-231 (breast), T24 (bladder), and OVCAR3 (ovarian). The tumorigenic and metastatic 5R Haras-transfected rat embryo fibroblast cell line responded to insulin with both chemotaxis and chemokinesis and was 100% of that seen for AMF. The ED50 for IGF-I in the carcinoma cell lines was in the order of I nM, but the magnitude of the responses at this concentration was 40% of the AMF-stimulated response, with the exception of the A2058 cells, which were maximally stimulated at I nM. IGF-II induced maximal motility of 75 to 130% of the AMF-stimulated response in the carcinoma lines with ED50 of less than or equal to 10 nM. IGF-II-stimulated motility in the carcinoma lines was predominantly chemotactic by modified checkerboard analysis. Cell pretreatment with pertussis toxin inhibited 90-100% of AMF-induced motility, whereas migration to the IPs was not pertussis toxinsusceptible. In growth studies, IGF-I induced mitogenesis up to 140% of basal media control growth. In general, maximal growth stimulation was seen at 100 nM IGF-I, and optimal migration was seen at 10 nM IGF-I. The IGFs are secreted by normal stroma in a number of organs that are common sites for primary and metastatic disease. Therefore, we suggest that IPs may be important homing and mitogenic signals for tumor cells in the process of invasion and metastasis and that the differential motility stimulation and respective mechanisms of action by these physiologically important agents may underlie the diversity of the metastatic process.
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PMID:Heterogeneity of the motility responses in malignant tumor cells: a biological basis for the diversity and homing of metastatic cells. 211 98


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