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

Humans ingest about 1 g of flavonoids daily in their diet, and they are increasingly being associated with cytoprotective antitumour properties. The mechanism(s) responsible for these effects have not yet been elucidated but may involve interaction with xenobiotic metabolising enzymes to alter the metabolic activation of potential carcinogens. We have investigated the effect of the flavonoids, quercetin (Q), myricetin (M) and epicatechin (E) on the growth, morphology and enzyme activities of MCF7 human breast cancer cells. Of the three flavonoids studied only Q caused a decrease in cell protein content and decreased the reduction of MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium). It also inhibited protein, DNA and RNA synthesis to the greatest extent. Q and M increased intracellular reduced glutathione (GSH) content, and Q altered the morphology of the cells after 24 h exposure to 25 microM. E and Q inhibited the O-deethylation of ethoxyresorufin (EROD) catalysed by cytochrome P450 CYPIA. In contrast, M increased the EROD reaction 2-fold. Q increased the activity of DT-diaphorase, NADPH cytochrome c reductase and glutathione reductase, while E increased only NADPH cytochrome c reductase activity. The effects on enzyme activities in vitro suggest that there is not only the potential for flavonoids to alter metabolic activation of carcinogens but also of therapeutically administered drugs in vivo. We are at present investigating the synergy between anti-cancer drugs and flavonoids in terms of anti-tumour efficacy.
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PMID:The effect of the flavonoids, quercetin, myricetin and epicatechin on the growth and enzyme activities of MCF7 human breast cancer cells. 992 Apr 63

Paclitaxel and methotrexate are active against a variety of solid tumors. Because of differences in their mechanisms of action and toxicity profiles, the combination of these two agents has clinical potential. Clinical studies of this combination are in progress. We studied the optimal schedule of paclitaxel and methotrexate in combination at various schedules in vitro using human lung cancer A549, breast cancer MCF7, ovarian cancer PA1, and colon cancer WiDr cells. Cells were simultaneously exposed to paclitaxel and methotrexate for 24 h and sequentially exposed to paclitaxel for 24 h followed by methotrexate for 24 h or vice versa. Cell growth inhibition after 5 days was determined by a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The effects of drug combinations at the concentration of drug that produced 80% cell growth inhibition (the IC80 level) were analyzed by the isobologram method. The simultaneous exposure to paclitaxel and methotrexate produced additive to antagonistic effects in the A549 and PA1 cells, and antagonistic effects in the MCF7 and WiDr cells. The sequential exposure to paclitaxel followed by methotrexate produced additive effects in all four cell lines. The reverse sequence produced synergistic effects in the A549, MCF7, and WiDr cells, and additive effects in the PA1 cells. These findings suggest that a sequential administration of methotrexate followed by paclitaxel may be the appropriate schedule for this combination. On the basis of the observed in vitro synergism, further in vivo and clinical studies are necessary to clarify the toxicity and proposed antitumor effects of this schedule.
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PMID:Schedule-dependent synergism and antagonism between paclitaxel and methotrexate in human carcinoma cell lines. 1006 68

In order to investigate the predictive value of in vitro MTT assay for directing chemotherapy of breast cancer patients, from 1992 to 1995, 156 advanced breast cancer patients who had evaluable lesions were recruited for a prospective study. Of them 83 had MTT assay before chemotherapy; the 73 patients in the MTT sensitive group received chemotherapy according to the result of the MTT assay. The other 10 patients in the MTT resistant group and 73 patients in the control group were given chemotherapy according to clinicians' discretion. The response rate in the MTT sensitive group was 76.7% (56/73). There was statistically significant difference as compared with 0 (0/10) in the MTT resistant group and 43.8% (32/73) in the control group. Between in vitro and in vivo, the overall coincident rate was 79.5% [(56 + 10)/83]. In the MTT sensitive group, the response rate of the subgroups of lesions and the chemotherapy regiments tended to be higher than that in the control group. Patients in the MTT sensitive group had longer response and survival than those in the control group. However, there was no statistical difference in the median response duration and the median survival between the two groups. Further exploration of in vitro chemosensitivity testing by MTT assay for patients with advanced breast cancer is warranted.
Breast Cancer Res Treat 1999 Jan
PMID:Predictive chemotherapy of advanced breast cancer directed by MTT assay in vitro. 1020 75

Surgical trauma and anesthesia may lead to the postoperative immunosuppression, the exact mechanism of which is still unresolved. Among various factors, the role of prostaglandine PGE2-mediated suppression was also proposed. We investigated the influence of surgery and two anesthetic regimes on lymphoproliferative response (LPR) to PHA and on NK cell activity (MTT) in breast cancer patients, as well as the effect of indomethacin, a PGE2 synthesis inhibitor, on these lymphocyte functions in vitro. In 36 previously untreated patients the lymphocyte functions were assayed before, 24 hours and seven days after the surgery. In regard to LPR, three distinct response patterns were observed: a) significant (p < 0.05) increase of initially lowered LPR; b) significant (p < 0.001) decrease of initially normal LPR 24 hours after operation, followed by normalization after seven days; c) no change of initially normal LPR. Indomethacin in vitro significantly (p < 0.05) enhanced the diminished LPR only before surgery, no effect being seen after the operation. The NK cell function was unaffected by surgery regardless the initial level of activity. Indomethacin had no effect on this lymphocyte function. There was no difference between the patient groups submitted to the different anesthetic regimes. In conclusion, our results show that surgical trauma variably affect the lymphocyte functions of cancer patients, the effect not being related to the particular anesthetic regime used. The PGE2-mediated suppression is not likely to be involved in postoperative immune function impairment.
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PMID:The influence of surgery and anesthesia on lymphocyte functions in breast cancer patients: in vitro effects of indomethacin. 1035 35

The determination of cellular content of octadecylphosphocholine (D-19391) and hexadecylphosphocholine (HePC, D-18506), two anticancer agents of the alkylphosphocholine group, using capillary gas chromatography is described. The compounds' cytotoxicity was first determined by the MTT [3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyltetrazolium] assay, being indicative for the concentration used in the uptake and retention measurements. D-19391 was added to the SK-BR-3 breast cancer cell line and HePC to the Molt-4 leukemia cell line in concentrations of, respectively, 18.6 and 15.0 microM, during a 36-h incubation period at 37 degrees C, 5% CO2. HePC uptake in the leukemia cells was followed by a 24-h reversibility test in drug-free medium. Subsequently, sample clean-up was performed on a weak cation-exchange column. For the quantitative analysis, HePC was used as internal standard for the D-19391 measurements and vice versa. Derivatization of the samples with trimethylsilylbromide was followed by capillary gas chromatographic analysis. From these data we conclude that our uptake results are quite similar with those of a previous study of HePC cellular uptake in the more resistant Caco-2T colon cancer cell line. Without having investigated the mechanism that underlies the cellular uptake results obtained, our study points to no direct correlation between the compounds' cellular uptake and their cytotoxic effects.
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PMID:Cellular uptake and retention measurements of alkylphosphocholines in the SK-BR-3 breast cancer and Molt-4 leukemia cell line using capillary gas chromatography. 1038 Jan 24

Grape seed proanthocyanidins are natural antioxidants which possess a broad spectrum of chemoprotective properties against free radicals and oxidative stress. In this study, we have assessed the cytotoxicity of a novel IH636 grape seed proanthocyanidin extract (GSPE) against MCF-7 human breast cancer cells, A-427 human lung cancer cells, CRL-1739 human gastric adenocarcinoma cells and K562 chronic myelogenous leukemic cells at 25 and 50 mg/lit concentrations for 0-72 h using cytomorphology and MTT cytotoxicity assay. In addition, we compared the effects on normal human gastric mucosal cells and normal J774A.1 murine macrophage cells with the effects on the cancer cell lines. Concentration- and time-dependent cytotoxic effects of GSPE were observed on the MCF-7 breast cancer, A-427 lung cancer and gastric adenocarcinoma cells. Following incubation of the MCF-7 cells with 25 mg/lit of the GSPE approximately 6.5, 30 and 43% inhibitions in cell growth were observed at 24, 48 and 72 h of incubation, respectively, while incubation of the MCF-7 cells with 50 mg/lit of the GSPE resulted in 11, 35 and 47% inhibition in cell growth at these same points, respectively. Similar results were observed in the A-427 and gastric adenocarcinoma cells. GSPE exhibited no cytotoxicity toward the neoplastic K562 myelogenous leukemic cells. However, GSPE enhanced the growth and viability of the normal human gastric mucosal cells and J774A.1 murine macrophage cells. These data demonstrate that GSPE exhibited cytotoxicity towards some cancer cells, while enhancing the growth and viability of the normal cells which were examined.
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PMID:The cytotoxic effects of a novel IH636 grape seed proanthocyanidin extract on cultured human cancer cells. 1044 8

Clinical studies of paclitaxel in combination with etoposide against solid tumors have been carried out. The combination schedules used in these studies are different. We studied the cytotoxic effects of paclitaxel with etoposide against four human cancer cell lines in vitro to determine the optimal schedule of this combination at the cellular level. Cells were exposed simultaneously to paclitaxel and to etoposide for 24 h or sequentially to one drug for 24 h followed by the other for 24 h, after which they were incubated in drug-free medium for 4 and 3 days, respectively. Cell growth inhibition was determined by an MTT reduction assay. The effects of drug combinations at concentrations producing 80% inhibition (IC(80)) were analyzed by the isobologram method of Steel and Peckham. The cytotoxic effect of paclitaxel and etoposide was cell line- and schedule-dependent. Simultaneous exposure to paclitaxel and etoposide for 24 h produced additive effects in the lung cancer cell line A549 and ovarian cancer PA1 cells, and antagonistic effects in the breast cancer cell line MCF7 and colon cancer WIDr cells. Sequential exposures to paclitaxel followed by etoposide and vice versa produced additive effects in all four cell lines. These results suggest that maximum cytotoxic effects can be obtained with sequential administration, but not simultaneous administration, of paclitaxel and etoposide. These findings may have important clinical implications for this combination.
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PMID:Schedule-dependent interactions between paclitaxel and etoposide in human carcinoma cell lines in vitro. 1050 11

Vinorelbine and paclitaxel are new anticancer agents that bind to distinct sites on tubulin and affect microtubules in opposite ways. Clinical studies of combinations of these agents have been in progress against breast cancer and some solid tumors. To clarify the optimal schedule for this combination, we studied the schedule-dependent cytotoxic effects of vinorelbine and paclitaxel against the human lung carcinoma cell line A549, the breast carcinoma cell line MCF7, the ovarian carcinoma cell line PA1, and the colon carcinoma cell line WiDr in vitro. Tumor cells were incubated with vinorelbine and paclitaxel simultaneously for both 24 h and 5 days. Cells were also incubated with vinorelbine for 24 h, followed by a 24-h exposure to paclitaxel and vice versa. Cell growth inhibition after 5 days was determined by MTT assay. The effects of drug combinations at the concentration producing 80% cell growth inhibition (IC80) were analyzed by the isobologram method (Steel and Peckham). The simultaneous exposures to vinorelbine and paclitaxel for both 24 h and 5 days produced additive effects for all four cell lines. The sequential exposure to vinorelbine followed by paclitaxel produced additive effects for the PA1 and WiDr cells, additive and antagonistic effects for the A549 cells, and antagonistic effects for the MCF7 cells. The sequential exposure to paclitaxel followed by vinorelbine produced additive effects for the A549, and PA1 cells, additive and antagonistic effects for the MCF7 cells, and antagonistic effects for the WiDr cells. Our findings suggest that the simultaneous rather than the sequential administration of vinorelbine and paclitaxel may be the optimal schedule for this combination of these two agents. Applications of this schedule dependency may be beneficial for the treatment of breast cancer and other solid tumors.
Breast Cancer Res Treat 1999 Jul
PMID:Schedule-dependent interactions between vinorelbine and paclitaxel in human carcinoma cell lines in vitro. 1051 45

The peroxisome proliferator-activated receptor gamma (PPARgamma) is a member of the nuclear receptor family of ligand-activated transcription factors. This study was designed to evaluate ligand activation of PPARgamma in human breast cancer cells. DNA binding by endogenous PPARgamma in gel shift assays and activation of PPARgamma by prostanoid and thiazolidinedione ligands in reporter gene assays differed between the cell lines. The PPARgamma ligands elicited an anti-proliferative effect in MTT proliferation assays. Our data point to a variable, cell-specific response to different gamma-ligands, which holds significance for further studies on the role of PPARgamma in mediating breast cancer growth and progression.
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PMID:Peroxisome proliferator-activated receptor gamma activation in human breast cancer. 1053 81

We have demonstrated previously that insulin-like growth factor binding protein (IGFBP)-3 alone has little growth inhibitory effect on Hs578T human breast cancer cells, but that it can dramatically accentuate the apoptotic response to the physiological trigger, ceramide, in an IGF-independent manner. We have now studied the potential of other IGFBPs (1-6) to interact with apoptotic signalling pathways. Hs578T cells were preincubated with a binding protein (100 ng/ml) for 24 h, followed by co-incubation of the binding protein with an apoptotic dose of ceramide or RGD-containing peptide for a further 24 h. Apoptosis was assessed using flow cytometry, MTT (3-[4,5-Dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide; thiazolyl blue) assay and morphological assessment. Binding protein profiles were determined using ligand and immunoblotting techniques. Each of the IGFBPs (1-6) alone had no significant (P > 0. 05) growth inhibitory effects relative to control cells. In contrast to IGFBP-3, which significantly (P < 0.05) accentuated C2-induced apoptosis, IGFBP-1, -2, and -6 had no effect, whereas IGFBP-4 and -5 each caused marked (P < 0.01) inhibition of ceramide-induced programmed cell death. Apoptosis induced by RGD was also significantly (P < 0.05) reduced by IGFBP-5, whereas IGFBP-3 had no effect. These data provide evidence to suggest that individual IGFBPs have specific IGF-independent effects and act differentially on apoptotic signalling pathways.
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PMID:Differential IGF-independent effects of insulin-like growth factor binding proteins (1-6) on apoptosis of breast epithelial cells. 1057 48


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