Antiprogestágenos como agentes terapéuticos en el tratamiento de cáncer de mama
There is evidence suggesting that antiprogestins might be used to treat selected breast cancers. The aim of our study was to evaluate the effect of using nanochemotherapeutic agents combined with mifepristone (MFP) using models showing different ratios of progesterone receptor (PR) isoforms A or B....
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| Formato: | Tesis doctoral acceptedVersion |
| Lenguaje: | Español |
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Facultad de Farmacia y Bioquímica
2015
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| Acceso en línea: | http://repositoriouba.sisbi.uba.ar/gsdl/cgi-bin/library.cgi?a=d&c=posgraafa&cl=CL1&d=HWA_1164 http://repositoriouba.sisbi.uba.ar/gsdl/collect/posgraafa/index/assoc/HWA_1164.dir/1164.PDF |
| Aporte de: |
| Sumario: | There is evidence suggesting that antiprogestins might be used to treat selected breast cancers. The aim of our study was to evaluate the effect of using nanochemotherapeutic agents combined with mifepristone (MFP) using models showing different ratios of progesterone receptor (PR) isoforms A or B. We demonstrated using murine mammary carcinomas of the MPA-induced model or xenografts of T47D-Y cells modified to express PRA or PRB, that MFP improved the therapeutic effects of pegylated doxorubicin liposomes or paclitaxel bound to albumin, only in tumors with higher levels of PRA than PRB. In these tumors MFP induced tissue remodeling increasing the number of functional vessels and favoring the accumulation of drugs inside the tumors. Interestingly, tumors with higher levels of PRA than PRB, were more sensitive to doxorubicin than to paclitaxel while those with the opposite ratio seemed to respond better to the latter. Preliminary experiments using tissue cultures of breast cancer samples with different PR isoform ratios failed to show additive effects. These results reinforce those obtained with the in vivo models. In this thesis we show that MFP might be used to increase the effect of nanochemotherapeutic agents of mammary carcinomas with higher levels of PRA than PRB. |
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