Optimizing the time of doxil injection to increase the drug retention in transplanted murine mammary tumors

Shaojin You, Lian Zuo, Wei LiExperimental Cancer Therapeutic Laboratory and Histopathology Core, Atlanta Research and Educational Foundation (151F), Atlanta VA Medical Center, Decatur, GA, USAAbstract: Sex hormonal milieus during the female fertility cycle modulate the tumor vascular permeability of...

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Autores principales:	Shaojin You, Lian Zuo, Wei Li
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2010
Materias:	Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/1e0583974b574c829650b600738fccc7
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spelling	oai:doaj.org-article:1e0583974b574c829650b600738fccc72021-12-02T00:47:25ZOptimizing the time of doxil injection to increase the drug retention in transplanted murine mammary tumors1176-91141178-2013https://doaj.org/article/1e0583974b574c829650b600738fccc72010-03-01T00:00:00Zhttp://www.dovepress.com/optimizing-the-time-of-doxil-injection-to-increase-the-drug-retention--a4135https://doaj.org/toc/1176-9114https://doaj.org/toc/1178-2013Shaojin You, Lian Zuo, Wei LiExperimental Cancer Therapeutic Laboratory and Histopathology Core, Atlanta Research and Educational Foundation (151F), Atlanta VA Medical Center, Decatur, GA, USAAbstract: Sex hormonal milieus during the female fertility cycle modulate the tumor vascular permeability of breast cancer. It has been proposed that the liposomal formulated doxorubicin (ie, Doxil), given at the menstrual/estrous stage with the predicted highest tumor vascular permeability, allows significantly increased drug retention in the breast tumor. In the current study, syngeneic murine 4T1 mammary tumors were established on the backs of female BALB/c mice and Doxil was administered at particular mouse estrous cycle stages. The results indicated that Doxil administration during certain times in the mouse estrous cycle was crucial for drug retention in 4T1 tumor tissues. Significantly higher drug concentrations were detected in the tumor tissues when Doxil was administered during the diestrus stage, as compared to when the drug injection was given at all other estrous stages. Our study also showed that the tumor-bearing mice exhibited nearly normal rhythmicity of the estrous cycle post drug injection, indicating the feasibility of continual injection of Doxil at the same estrous cycle stage. By using 4T1 cells cultured in vitro, we showed that progesterone (P4) significantly inhibited cell proliferation and the production of six tumor-derived cytokines, eg, sTNF-RI, CXCL-16, GM-CSF, MIP-1&alpha;, MIP-1&gamma;, and Flt3-L. Some of these factors have been shown to be vascular modulators in diverse tissues. In this report, we demonstrated that the concentration of P4 in the plasma and/or estrous cycle stage of 4T1 tumor-bearing mice can be used to select the best time for administrating the liposomal anticancer drugs.Keywords: progesterone, menstrual cycle, mouse mammary tumor, Doxil, breast cancer therapy Shaojin YouLian ZuoWei LiDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2010, Iss default, Pp 221-229 (2010)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine (General) R5-920
spellingShingle	Medicine (General) R5-920 Shaojin You Lian Zuo Wei Li Optimizing the time of doxil injection to increase the drug retention in transplanted murine mammary tumors
description	Shaojin You, Lian Zuo, Wei LiExperimental Cancer Therapeutic Laboratory and Histopathology Core, Atlanta Research and Educational Foundation (151F), Atlanta VA Medical Center, Decatur, GA, USAAbstract: Sex hormonal milieus during the female fertility cycle modulate the tumor vascular permeability of breast cancer. It has been proposed that the liposomal formulated doxorubicin (ie, Doxil), given at the menstrual/estrous stage with the predicted highest tumor vascular permeability, allows significantly increased drug retention in the breast tumor. In the current study, syngeneic murine 4T1 mammary tumors were established on the backs of female BALB/c mice and Doxil was administered at particular mouse estrous cycle stages. The results indicated that Doxil administration during certain times in the mouse estrous cycle was crucial for drug retention in 4T1 tumor tissues. Significantly higher drug concentrations were detected in the tumor tissues when Doxil was administered during the diestrus stage, as compared to when the drug injection was given at all other estrous stages. Our study also showed that the tumor-bearing mice exhibited nearly normal rhythmicity of the estrous cycle post drug injection, indicating the feasibility of continual injection of Doxil at the same estrous cycle stage. By using 4T1 cells cultured in vitro, we showed that progesterone (P4) significantly inhibited cell proliferation and the production of six tumor-derived cytokines, eg, sTNF-RI, CXCL-16, GM-CSF, MIP-1&alpha;, MIP-1&gamma;, and Flt3-L. Some of these factors have been shown to be vascular modulators in diverse tissues. In this report, we demonstrated that the concentration of P4 in the plasma and/or estrous cycle stage of 4T1 tumor-bearing mice can be used to select the best time for administrating the liposomal anticancer drugs.Keywords: progesterone, menstrual cycle, mouse mammary tumor, Doxil, breast cancer therapy
format	article
author	Shaojin You Lian Zuo Wei Li
author_facet	Shaojin You Lian Zuo Wei Li
author_sort	Shaojin You
title	Optimizing the time of doxil injection to increase the drug retention in transplanted murine mammary tumors
title_short	Optimizing the time of doxil injection to increase the drug retention in transplanted murine mammary tumors
title_full	Optimizing the time of doxil injection to increase the drug retention in transplanted murine mammary tumors
title_fullStr	Optimizing the time of doxil injection to increase the drug retention in transplanted murine mammary tumors
title_full_unstemmed	Optimizing the time of doxil injection to increase the drug retention in transplanted murine mammary tumors
title_sort	optimizing the time of doxil injection to increase the drug retention in transplanted murine mammary tumors
publisher	Dove Medical Press
publishDate	2010
url	https://doaj.org/article/1e0583974b574c829650b600738fccc7
work_keys_str_mv	AT shaojinyou optimizingthetimeofdoxilinjectiontoincreasethedrugretentionintransplantedmurinemammarytumors AT lianzuo optimizingthetimeofdoxilinjectiontoincreasethedrugretentionintransplantedmurinemammarytumors AT weili optimizingthetimeofdoxilinjectiontoincreasethedrugretentionintransplantedmurinemammarytumors
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Optimizing the time of doxil injection to increase the drug retention in transplanted murine mammary tumors

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