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Query: UMLS:C0006142 (breast cancer)
 160,383 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Germline mutations of the tumour suppressor gene BRCA1 are involved in the predisposition and development of breast cancer and account for 20-45% of all hereditary cases. There is an increasing evidence that these tumours are characterised by a specific phenotype and pattern of gene expression. We have hypothesised that differences in chemosensitivity might parallel molecular heterogeneity of hereditary and sporadic breast tumours. To this end, we have investigated the chemosensitivity of the BRCA1-defective HCC1937 breast cancer cell line, and the BRCA1-competent MCF-7 (hormone-sensitive) and MDA-MB231 (hormone-insensitive) breast cancer cell lines using the MTT assay. The 50% inhibitory concentration (IC(50)) for the individual compounds were derived by interpolate plot analysis of the logarithmic scalar concentration curve after a 48 h exposure. HCC1937 cells were significantly (P<0.005) more sensitive to cisplatin (CDDP) (IC(50) : 30-40 microM) compared with MCF-7 (IC(50) : 60-70 microM) and MDA-MB231 (IC(50) : 90-100 microM) cells. On the other hand, BRCA1-defective breast cancer cells were significantly less sensitive to doxorubicin (Dox) (IC(50) : 45-50 microM) compared with MCF-7 (IC(50) : 1-5 microM) and MDA-MB231 (IC(50) : 5-10 microM) (P<0.02), as well as to paclitaxel (Tax) (IC(50) : >2 microM for HCC1937, 0.1-0.2 microM for MCF-7 and 0.01-0.02 microM for MDA-MB231) (P<0.001). Full-length BRCA1 cDNA transfection of BRCA1-defective HCC1937 cells led to the reconstituted expression of BRCA1 protein in HCC1937/(WT)BRCA1-derived cell clone, but did not reduce tumour cell growth in soft agar. BRCA1 reconstitution reverted the hypersensitivity to CDDP (P<0.02), and restored the sensitivity to Dox (P<0.05) and Tax (P<0.001), compared with parental HCC1937 cells. Taken together, our findings suggest a specific chemosensitivity profile of BRCA1-defective cells in vitro, which is dependent on BRCA1 protein expression, and suggest prospective preclinical and clinical investigation for the development of tailored therapeutical approaches in this setting.
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PMID:BRCA1 expression modulates chemosensitivity of BRCA1-defective HCC1937 human breast cancer cells. 1269 98

The study was designed to explore the estrogenic activity of environmental disrupters [n-4-noniphenol (NP), bisphenol A (bisA) and dibutylphthalate (DBP)]. Estrogen-respective breast cancer cell line T47D was grown in DMEM medium containing 10% bovine serum. Five days before the addition of the test compounds, the cell were washed in phosphate-buffered saline, and the medium was substituted with a phenol red-free DMEM medium containing 5% dextran charcoal-stripped FBS. The respective test compound was added in fresh medium and the control cell received only the vehicle (ethanol). The proliferation of T47D cells was analyzed by MTT assay, 3H-TdR incorporation assay and flow sytometer. The results indicated that, compared with the EtOH control cell, the test compounds (n-4-noniphenol, Bisphenol A and dibutylphthalate), like estradiol, markedly enhanced the proliferation of T47D cell and the metaphase of cell division, and the results showed time-dependent and dose-dependent model. These data showed that the tested chemicals could enhance the proliferation of human cervix cancer cell in vitro. This might hinted that these chemicals possessed estrogenic activity and they might play their estrogen through estrogenic receptor.
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PMID:[Estrogenic activity of some environmental chemicals]. 1273 Dec 75

Modulation of cancer chemotherapeutic drugs has been attempted to increase efficacy and overcome resistance to the chemotherapeutic agent. Studies have shown schedule-dependent interactions in combined use of chemotherapeutic drugs. Mitoguazone (MGBG), an old drug with possible modulating activity, was used in combination with gemcitabine, a relatively new cancer drug, in treating tissue cultured human breast cancer cells and mammary rat tumors. Tissue cultured BOT-2 cancer cells were first treated with varying concentrations of gemcitabine and MGBG, independently. Combinations of the two drugs were then used with different scheduled administrations. Marked synergistic activity was found between gemcitabine and MGBG when the MGBG was given first, followed by gemcitabine 24 hours later. A non-toxic dose of MGBG enhanced the toxicity of gemcitabine by eight orders of magnitude using MTT assays in the tissue cultured human breast cancer cell study. The sequential administration of MGBG and gemcitabine also increased the survival rate of rats bearing mammary tumors in our pilot animal study.
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PMID:Synergistic effect of sequential administration of mitoguazone (MGBG) and gemcitabine in treating tissue cultured human breast cancer cells and mammary rat tumors. 1274 87

The inhibitory effect of saponins from Tribulus terrestris (STT) on Bcap37 breast cancer cell line were determined by cell growth curve, MTT assay, protein content assay and morphological observation. The results showed that STT had potent inhibitory effect on Bcap-37 cell line in a concentration-dependent manner. Bcap-37 cell exhibited morphological alteration, namely, cells got round and shrunk, nuclei contracted after treating with STT.
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PMID:[The inhibitory effect of saponins from Tribulus terrestris on Bcap-37 breast cancer cell line in vitro]. 1279 20

The current treatment of breast carcinomas recognizes the importance of combination therapy in order to increase efficacy and decrease side effects of conventional chemotherapy. Inositol hexaphosphate (IP6), a naturally occurring polyphosphorylated carbohydrate, has shown a significant anti-cancer effect in various in vivo and in vitro models, including breast cancer. In this study, we investigated the in vitro growth inhibitory activity of IP6 in combination with adriamycin or tamoxifen, against three human breast cancer cell lines: estrogen receptor (ER) alpha-positive MCF-7, ER alpha-negative MDA-MB 231 and adriamycin-resistant MCF-7 (MCF-7/Adr) using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Much lower concentrations of IP6 were required after 96 h of treatment to inhibit the growth of MCF-7/Adr cells than MCF-7 cells; the IC50 for MCF-7/Adr cells was 1.26 mM compared to 4.18 mM for MCF-7 cells. The ER-negative MDA-MB 231 cells were also highly sensitive to IP6 with IC50 being 1.32 mM. To determine the effects of IP6 in combination with either adriamycin or tamoxifen, the median effect principle and Webb's fraction method were used to determine the combination index (CI) and the statistical differences. Growth suppression was markedly increased when IP6 was administered prior to the addition of adriamycin, especially against MCF-7 cells (CI = 0.175 and p < 0.0001). Synergism was also observed when IP6 was administered after tamoxifen in all three cell lines studied (CI = 0.343, 0.701 and 0.819; p < 0.0001, p = 0.0003 and 0.0241 for MCF-7/Adr, MCF-7 and MDA-MB 231, respectively). The growth of primary culture of breast cancer cells from patients was inhibited by IP6 with LC50 values ranging from 0.91 to 5.75 mM (n = 10). Our data not only confirm that IP6 alone inhibits the growth of breast cancer cells; but it also acts synergistically with adriamycin or tamoxifen, being particularly effective against ER alpha-negative cells and adriamycin-resistant cell lines.
Breast Cancer Res Treat 2003 Jun
PMID:Inositol hexaphosphate (IP6) enhances the anti-proliferative effects of adriamycin and tamoxifen in breast cancer. 1284 14

The in vitro cytotoxic activity profile of nine novel phenylarsonic acid (CAS 98-05-5, PAA) compounds against 17 human cancer cell lines including (a) ovarian cancer cell lines ES-2, PA-1, CAOV-3, OVCAR-3, (b) testicular cancer cell lines Ntera-2, Tera-2, N2NICP, 833K, and 64CP, (c) multiple myeloma cell lines ARH77, HS-Sultan, RPMI-8226, and U266, and (d) acute lymphoblastic leukemia (ALL) cell lines NALM-6, MOLT-3, ALL-1, and RS4; 11, was determined by the MTT assay. The lead compounds, 2-methylthio-4-[(4'-aminophenylazo)-phenylarsonic acid] pyrimidine (PHI-370) and 2-methylthio-4-(4'-phenylarsonic acid)-aminopyrimidine (PHI-380) caused apoptotic death in all 17 cancer cell lines at low micromolar concentrations, as documented by TUNEL assays and confocal laser scanning microscopy. PHI-380 was also tested and found to be very active against primary tumor cells isolated from surgical biopsy specimens of 14 patients with therapy-refractory non-small cell lung cancer, breast cancer, colon cancer, lymphoma, hepatoblastoma, or Wilm's tumor as well. Because of their broad-spectrum and potent anticancer activity and ability to induce apoptosis in primary tumor cells from therapy-refractory cancer patients, PAA compounds such as PHI-370 and PHI-380 may provide the basis for effective salvage regimens for patients with recurrent cancer.
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PMID:Phenylarsonic acid compounds with broad-spectrum and potent cytotoxic activity against human cancer cells. 1287 14

Solanum nigrum L. (SNL) has been traditionally used as a herbal plant, whose fruit is believed to have anti-tumor properties, although the mechanism for the activity remains to be elucidated. In this study, we prepared an ethanol extract from ripe fruits of SNL and investigated the mechanism involved in its growth-inhibitory effect on MCF-7 human breast cancer cells. Results from proliferation assay using tritium uptake showed that the proliferative capacity of MCF-7 cells was strongly suppressed in the presence of SNL ethanol extract. This was further confirmed through MTT assay and trypan blue exclusion experiments, which showed a very close correlation between the SNL extract concentration and the surviving cell numbers. The SNL extract-mediated suppression of cell growth was verified to be apoptotic, based on the appearance of DNA laddering, increase in DNA fragmentation, and low fluorescence intensity in nuclei after propidium iodide staining of the cells. Furthermore, the SNL extract was revealed to be a potential scavenger of hydroxyl radicals and DPPH radicals rather than superoxide anions. Collectively, our findings suggest that SNL fruit extract could be used as an anti-oxidant and cancer chemo-preventive material.
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PMID:Ripe fruit of Solanum nigrum L. inhibits cell growth and induces apoptosis in MCF-7 cells. 1290 77

OVS1 monoclonal antibody (MAb) produced against ovarian cancer is currently used to identify mucinous cystadenocarcinoma antigen as a tumor marker secreted in serum. The potential of OVS1 MAb in ovarian cancer treatment was studied by evaluating the induction of cytotoxicity and apoptosis of SKOV3 ovarian cancer and BT549 breast cancer cell lines induced by OVS1. Paclitaxel, an antitumor drug, was used as positive control and applied as a combined drug together with OVS1 MAb. OVS1 MAb and paclitaxel were found by MTT assay to induce cytotoxicity against both cell lines. The ED50 of OVS1 MAb were 26.25 and 25.00 microg/ml and of paclitaxel were 21.88 and 9.20 nM against SKOV3 and BT549 cell lines, respectively. The quantitative amount of cells determined by fluorimetric assay was correlated to the results of the MTT assay. The combined application of OVS1 MAb and paclitaxel on these two cell lines resulted in a greater cytotoxicity than observed by either agent alone. OVS1 MAb and paclitaxel applied against both cell lines induced the morphological changes of apoptotic cell death at 24 hours visualized by two color fluorescence dyes, Ho33342 and propidium iodide. Combination of the two substances enhanced the rate of apoptosis compared to either OVS1 MAb or paclitaxel given alone. DNA fragmentation was detected in an agarose gel electrophoresis after treating cells with OVS1 MAb and paclitaxel at 24 hours. These findings on the induction of cytotoxicity and apoptosis by OVS1 MAb on cancer cell lines have implications on the potential application of OVS1 MAb for clinical therapy.
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PMID:Cytotoxicity and apoptosis of ovarian and breast cancer cell lines induced by OVS1 monoclonal antibody and paclitaxel. 1293 49

A series of amidine analogues of chlorambucil (9-12), where 5-[4-(N-alkylamidino)phenyl]-2-furancarboxamide and the chlorambucil moiety are linked by a NH(CH(2))(2)NH chain, was synthesized and their cytotoxicity has been tested against the growth of human breast cancer MCF-7 cells. Evaluation of the cytotoxicity of compounds 9-12 employing a MTT assay and inhibition of [(3)H]thymidine incorporation into DNA demonstrated that these conjugates were more active than chlorambucil. Data from the ethidium displacement assay indicated that these compounds bind in the minor groove of DNA and show moderate specificity for AT base pairs. Compounds 9-12 were potent topoisomerase II inhibitors, with 50% inhibitory concentrations (IC(50))ranging from 10 to 40 microM. The cytotoxicity of the compounds 9-12 correlates with their DNA-binding affinities and their relative potency as topoisomerase II inhibitors. Altogether, these data suggest (i) that the cytotoxic activity of compounds 9-12 may be due to the combined effects of alkylation, DNA-minor groove binding, and (ii) that N-(2-aminoethyl)-5-(4-N-alkylamidinophenyl)-2-furancarboxamides (5-8) ligands are suitable linkers that favors DNA targeting by chlorambucil derivatives.
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PMID:Structure-activity studies of novel amidine analogues of chlorambucil: correlation of cytotoxic activity with DNA-binding affinity and topoisomerase II inhibition. 1295 17

The proliferative effects of thirty Oriental medicinal herbs on MCF-7 (estrogen-sensitive breast cancer cell line) and ROS 17/2.8 osteoblast-like cells were determined using the MTT assay. Methanol extracts from several herbs was found to show proliferative activity on the above two cell lines in the range of 5 to 100 microg/mL. Among these active herbs, the methanol extract from the rhizomes of Drynaria fortunei showed the most potent proliferative activity, and the cell proliferations were significantly increase by 136 and 158% in the MCF-7 and ROS 17/2.8 cells, respectively, when treated with 100 microg/mL. Through a bioassay-guided separation, eight flavonoids, including four new flavan-3-ols and two propelargonidins, together with the known (-)-epiafzelechin and naringin, were isolated. Their chemical structures were characterized as (-)-epiafzelechin (1), (-)-epiafzelechin-3-O-beta-D-allopyranoside (2), (-)-epiafzelechin-3-O-(6"-O-acetyl)-beta-D-allopyranoside (3), 4beta-carboxymethyl-(-)-epiafzelechin methyl ester (4), 4beta-carboxymethyl-(-)-epiafzelechin sodium salt (5), naringin (6), (-)-epiafzelechin-(4beta-->8)-4beta-carboxymethylepiafzelechin methyl ester (7) and (-)epiafzelechin-(4beta-->8, 2beta-->O-->7)-epiafzelechin-(4beta-->8)-epiafzelechin (8) by extensive 1D and 2D NMR spectroscopy. Most of these flavonoids, in the range of 10(-15) to approximately 10(-6) M, accelerated the proliferation of MCF-7 cell, with compounds 7 and 8, in the range of 10(-15) to approximately 10(-12) M, showing especially potent proliferation effects. Meanwhile, seven flavonoids, with the exception of compound 4, stimulated the proliferation of ROS 17/2.8 cells in the range of 10(-15) to approximately 10(-6) M, with compounds 5-8 especially accelerating the proliferation, in dose-dependent manners (10(-15) to approximately 10(-9) M), and their proliferative effect was much stronger than that of E2 and genistein. These results suggest that propelargonidin dimers and trimers isolated from the rhizomes of Drynaria fortunei may be useful as potential phytoestrogens, which play important physiological roles in the prevention of postmenopausal osteoporosis.
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PMID:Proliferative effects of flavan-3-ols and propelargonidins from rhizomes of Drynaria fortunei on MCF-7 and osteoblastic cells. 1296 97


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