Toremifene: pharmacologic and pharmacokinetic basis of reversing multidrug resistance.

1989 ◽  
Vol 7 (9) ◽  
pp. 1359-1364 ◽  
Author(s):  
M W DeGregorio ◽  
J M Ford ◽  
C C Benz ◽  
V J Wiebe
Keyword(s):  
Estrogen Receptor Status ◽  
Plasma Concentrations ◽  
Multidrug Resistant ◽  
High Dose ◽  
Human Breast ◽  
Human Breast Cell Line ◽  
Human Breast Cell ◽  
Mcf 7 ◽  
Resistant Cells

Triphenylethylene compounds, such as tamoxifen, have shown chemosensitizing activity independent of estrogen receptor status in doxorubicin-resistant cells. We examined the chemosensitizing activity of a new triphenylethylene, toremifene, and its major metabolites in a doxorubicin-resistant human breast cell line, MCF-7/DOX. In addition, we examined the chemosensitizing activity of unbound plasma toremifene and its metabolites isolated from patients treated with toremifene doses of 20 to 400 mg/d. MCF-7/DOX cells were exposed to ultrafiltrate plasma specimens in the absence and presence of doxorubicin. These latter studies were single-blinded. Toremifene and its major metabolites were capable of sensitizing multidrug-resistant cells to doxorubicin. The degree of chemosensitizing activity in vitro correlated with the plasma concentrations of toremifene and its metabolites (P less than .05). Plasma samples isolated from patients receiving high-dose toremifene (400 mg/d) had the greatest chemosensitizing activity. We present evidence that toremifene and its metabolites can sensitize resistant MCF-7/DOX cells to doxorubicin, that this effect is concentration-dependent, and that sensitizing activity can be detected at clinically achieved concentrations.

scholarly journals Soya phytonutrients act on a panel of genes implicated with BRCA1and BRCA2 oncosuppressors in human breast cell lines

2006 ◽  
Vol 95 (2) ◽  
pp. 406-413 ◽  
Author(s):  
Bertrand Caëtano ◽  
Ludovic Le Corre ◽  
Nassera Chalabi ◽  
Laetitia Delort ◽  
Yves-Jean Bignon ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Lines ◽  
Response To Treatment ◽  
Breast Cancer Cell Lines ◽  
Human Breast ◽  
Ki 67 ◽  
Breast Cell Lines ◽  
Human Breast Cell ◽  
Mcf 7

Breast cancer is the most common cancer in women and a significant cause of death. Mutations of the oncosuppressor genes BRCA1 and BRCA2 are associated with a hereditary risk of breast cancer, and dysregulation of their expression has been observed in sporadic cases. Soya isoflavones have been shown to inhibit breast cancer in studies in vitro, but associations between the consumption of isoflavone-containing foods and breast cancer risk have varied in epidemiological studies. Soya is a unique source of the phytoestrogens daidzein (4′,7-dihydroxyisoflavone) and genistein (4′,5,7-trihydroxyisoflavone), two molecules that are able to inhibit the proliferation of human breast cancer cells in vitro. The aim of the present study was to determine the effects of genistein (5μg/ml) and daidzein (20μg/ml) on transcription in three human breast cell lines (one dystrophic, MCF10a, and two malignant, MCF-7 and MDA-MB-231) after 72h treatment. The different genes involved in the BRCA1 and BRCA2 pathways (GADD45A, BARD1, JUN, BAX, RB1, ERα, ERβ, BAP1, TNFα, p53, p21Waf1/Cip1, p300, RAD51, pS2, Ki-67) were quantified by real-time quantitative RT-PCR, using the TaqMan method and an ABI Prism 7700 Sequence Detector (Applied Biosystems). We observed that, in response to treatment, many of these genes were overexpressed in the breast cancer cell lines (MCF-7 and MDA-MB-231) but not in the dystrophic cell line (MCF10a).

The influence of lycopene on the proliferation of human breast cell line (MCF-7)

2007 ◽  
Vol 21 (2) ◽  
pp. 217-223 ◽  
Author(s):  
F. Fornelli ◽  
A. Leone ◽  
I. Verdesca ◽  
F. Minervini ◽  
G. Zacheo
Keyword(s):  
Cell Line ◽  
Breast Cell Line ◽  
Human Breast ◽  
Human Breast Cell Line ◽  
Human Breast Cell ◽  
Mcf 7

scholarly journals In VitroPharmacodynamics of Simulated Pulmonary Exposures of Tigecycline Alone and in Combination againstKlebsiella pneumoniaeIsolates Producing a KPC Carbapenemase

2011 ◽  
Vol 55 (4) ◽  
pp. 1420-1427 ◽  
Author(s):  
Dora E. Wiskirchen ◽  
Pornpan Koomanachai ◽  
Anthony M. Nicasio ◽  
David P. Nicolau ◽  
Joseph L. Kuti
Keyword(s):  
Multidrug Resistant ◽  
Pharmacodynamic Model ◽  
High Dose ◽  
Prolonged Infusion ◽  
Bacterial Killing ◽  
Epithelial Lining Fluid ◽  
Multidrug Resistant Organisms ◽  
Time Kill ◽  
Additional Reduction

ABSTRACTMultidrug-resistantKlebsiella pneumoniaestrains that produce a serine carbapenemase (KPC) are emerging worldwide, with few therapeutic options that retain consistent susceptibility. The objective of this study was to determine the effect of combination therapy with tigecycline versus tigecycline alone against KPC-producing isolates (KPC isolates). Anin vitropharmacodynamic model was used to simulate adult steady-state epithelial lining fluid concentrations of tigecycline (50 mg every 12 h) given alone and in combination with either meropenem (2 g by 3-hour infusion every 8 h) or rifampin (600 mg every 12 h). Five KPC isolates with various phenotypic profiles were exposed over 48 h. Time-kill curves were constructed, and the areas under the bacterial killing and regrowth curves (AUBCs) were calculated. No regimens tested were able to maintain bactericidal reductions in CFU over 48 h. The AUBCs for tigecycline and meropenem monotherapies at 48 h ranged from 375.37 to 388.11 and from 348.62 to 383.83 (CFU-h/ml), respectively. The combination of tigecycline plus meropenem significantly reduced the AUBCs at 24 and 48 h for isolates with tigecycline MICs of ≤2 μg/ml and meropenem MICs of ≤16 μg/ml (P< 0.001) but added no additional activity when the meropenem MIC was 64 μg/ml (P= 0.5). Rifampin provided no additional reduction in CFU or AUBC over tigecycline alone (P= 0.837). The combination of tigecycline with high-dose, prolonged-infusion meropenem warrants further study as a potential treatment option for these multidrug-resistant organisms.

scholarly journals Synthesis and Experimental Validation of New Designed Heterocyclic Compounds with Antiproliferative Activity versus Breast Cancer Cell Lines MCF-7 and MDA-MB-231

2017 ◽  
Vol 2017 ◽  
pp. 1-10 ◽  
Author(s):  
Vincenza Barresi ◽  
Carmela Bonaccorso ◽  
Domenico A. Cristaldi ◽  
Maria N. Modica ◽  
Nicolò Musso ◽  
...  
Keyword(s):  
Cell Line ◽  
Cell Lines ◽  
Cancer Cell ◽  
Anticancer Agents ◽  
Cancer Cell Line ◽  
Breast Cancer Cell Lines ◽  
Design And Synthesis ◽  
Human Breast Cell ◽  
Mcf 7

Recent drug discovery efforts are highly focused towards identification, design, and synthesis of small molecules as anticancer agents. With this aim, we recently designed and synthesized novel compounds with high efficacy and specificity for the treatment of breast tumors. Based on the obtained results, we constructed a Volsurf+ (VS+) model using a dataset of 59 compounds able to predict the in vitro antitumor activity against MCF-7 cancer cell line for new derivatives. In the present paper, in order to further verify the robustness of this model, we report the results of the projection of more than 150 known molecules and 9 newly synthesized compounds. We predict their activity versus MCF-7 cell line and experimentally verify the in silico results for some promising chosen molecules in two human breast cell lines, MCF-7 and MDA-MB-231.

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