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FF-10832 enables long survival via effective gemcitabine accumulation in a lethal murine peritoneal dissemination model.


ABSTRACT: Chemotherapy has been the treatment of choice for unresectable peritoneal dissemination; however, it is difficult to eradicate such tumors because of poor drug delivery. To solve this issue, we developed FF-10832 as liposome-encapsulated gemcitabine to maintain a high concentration of gemcitabine in peritoneal tumors from the circulation and ascites. A syngeneic mouse model of peritoneal dissemination using murine Colon26 cell line was selected to compare the drug efficacy and pharmacokinetics of FF-10832 with those of gemcitabine. Despite the single intravenous administration, FF-10832 treatment enabled long-term survival of the lethal model mice as compared with those treated with gemcitabine. Pharmacokinetic analysis clarified that FF-10832 could achieve a more effective gemcitabine delivery to peritoneal tumors owing to better stability in the circulation and ascites. The novel liposome-encapsulated gemcitabine FF-10832 may be a curative therapeutic tool for cancer patients with unresectable peritoneal dissemination via the effective delivery of gemcitabine to target tumors.

SUBMITTER: Higuchi T 

PROVIDER: S-EPMC6726679 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

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FF-10832 enables long survival via effective gemcitabine accumulation in a lethal murine peritoneal dissemination model.

Higuchi Tamami T   Yokobori Takehiko T   Takahashi Ryo R   Naito Tomoharu T   Kitahara Hiromu H   Matsumoto Takeshi T   Kakinuma Chihaya C   Hagiwara Shinji S   Kuwano Hiroyuki H   Shirabe Ken K   Asao Takayuki T  

Cancer science 20190801 9


Chemotherapy has been the treatment of choice for unresectable peritoneal dissemination; however, it is difficult to eradicate such tumors because of poor drug delivery. To solve this issue, we developed FF-10832 as liposome-encapsulated gemcitabine to maintain a high concentration of gemcitabine in peritoneal tumors from the circulation and ascites. A syngeneic mouse model of peritoneal dissemination using murine Colon26 cell line was selected to compare the drug efficacy and pharmacokinetics o  ...[more]

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