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Stimulation of hematopoiesis by carboplatin-liposomes

Item Type:Article
Title:Stimulation of hematopoiesis by carboplatin-liposomes
Creators Name:Fichtner, I., Reszka, R., Becker, M., Lemm, M., Richter, J. and Rudolph, M.
Abstract:Following a single intravenous (i.v.) injection of carboplatin-liposomes (REV, HEPC:CH 1: 0.25) into mice peripheral white blood cell (WBC) counts increase to more than 30 000 x 106/ml. This elevation is observed between the 14th and 30th day after administration and significantly higher than normal values are registered even at day 42. Differentiation of WBC reveals both an increase of granulocytes, lymphocytes and monocytes. In parallel, platelets and erythrocytes are reduced moderately. Free carboplatin, empty liposomes or cis-platin-liposomes never caused a similar pharmacological behavior. This increase in peripheral WBC counts is accompanied by a distinct reduction of cell counts in spleens and bone marrow of the same mice. We suppose that carboplatin-liposomes (CPL) are taken up by monocytes/macrophages as their natural target. Within these cells cytokines are induced and released which secondarily lead to an induction of haematopoietic growth factors. This hypothesis is strengthened by the fact that in vitro cultivated macrophages release tumor necrosis factor following contact with carboplatin-liposomes over a period of 4 - 6 hours and that mice after administration react with a change in body temperature (probably due to interleukin-1). A combined treatment of mice with cyclophosphamide (150 mg/kg, i.p.) and carboplatin-liposomes prevents the cytostatic-induced leukopenia. These described effects let us suppose that carboplatin-liposomes can be used as a rescue method in high-dose chemo- or irradiation therapy of cancer.
Keywords:Carboplatin, Liposomes, Hematopoiesis, Animals, Mice
Source:Journal of Liposome Research
Publisher:Taylor & Francis
Page Range:43-69
Date:March 1994
Official Publication:https://doi.org/10.3109/08982109409037029

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