CARBOPLATIN-LIPOSOMES (CPL) IN IMMUNODEFICIENT MICE - IMPROVED ANTITUMOR-ACTIVITY FOR BREAST CARCINOMAS AND STIMULATION OF HEMATOPOIESIS

被引：5

作者：

FICHTNER, I

RESZKA, R

GOAN, SR

NAUNDORF, H

机构：

[1] Max-Delbrtick-Center of Molecular Medicine, Berlin, 13125

来源：

MEDICAL ONCOLOGY | 1994年 / 11卷 / 3-4期

关键词：

LIPOSOMES; CARBOPLATIN; ANTITUMOR ACTIVITY; HEMATOPOIESIS; NUDE MICE; SCID MICE;

D O I：

10.1007/BF02999858

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 [肿瘤学];

摘要：

Carboplatin-liposomes (CPL) have been shown to possess a strong stimulatory activity on the hematopoiesis in immunocompetent mice. As we were interested in studying this pharmacological characteristic in parallel with any antitumour effects which might be expected for the encapsulated cytostatic, we used a panel of six human breast carcinomas xenotransplanted to nude mice. The antitumor activity as well as the hematopoietic effects of the vesicles were studied in comparison to, and in combination with, the free drug. Carboplatin was encapsulated into reverse phase evaporation vesicles (REV) and injected i.p. as a single dose of 75 mg kg(-1) into tumor-free and breast-carcinoma-bearing animals, respectively. Following a single application of CPL in nude mice, a significant increase of the WBC numbers to about three times for that of the normal level could be observed over a period of at least 28 days. The elevation was due to an increase in both circulating granulocytes and lymphocytes. The peripheral effect was accompanied by a relative decrease of spleen cellularity, while the number of bone marrow cells was hardly affected. There was no influence detectable on circulating blood cells in SCID mice. However, a rather high toxicity of CPL for this immunodeficient mouse strain was noticed. In the panel of breast carcinomas used, free carboplatin and CPL displayed a different pattern of therapeutic efficiencies. In four of the five tumor models tested, a combination of the free with the liposomal drug showed a significant inhibition of tumor growth while effectively preventing a drug-induced leukopenia. As a result, CPL may be recommended in tumor therapy protocols for future clinical trials in order to relieve a cytostatic-induced bone marrow suppression.

引用

页码：111 / 119

页数：9

共 23 条

[1]

Fichtner I., Reszka R., Becker M., Lemm M., Richter J., Berger I., Rudolph M., Stimulation of hematopoiesis by Carboplatin-liposomes, J Lipos Res, 4, (1993)

[2]

Fichtner I., Reszka R., Schtitt M., Rudolph M., Becker M., Lemm M., Richter J., Berger I., Carboplatin-Liposomes as Activators of Hematopoiesis, Oncol Res, 5, (1993)

[3]

Naundorf H., Rewasowa E.C., Fiehtner I., Btittner B., Becker M., Gorlich M., Characterization of two human mammary carcinomas, MT-1 and MT-3, suitable for in vivo testing of ether lipids and their derivatives, Breast Cancer Res Trest, 23, (1992)

[4]

Widmaier R., Wildner G.R., Papsdorf G., Graffi A., Uber eine neue in vitro unbegrenzt wachsende Zellinie, MaTu, yon Mammatumorzellen des Menschen, Arch GeschwulsO~orsch, 44, (1974)

[5]

Naundorf H., Fichtner I., BiJttner B., Frege J., Establishment and characterization of a new human oestradiol-and-progesterone-receptorpositive mammary carcinoma serially transplantable in nude mice, J Cancer Res Clin Oncol, 119, (1992)

[6]

Pantelouris E.M., Observations on the immunobiology of ’nude’ mice, Immunology, 20, (1971)

[7]

Waki S., Suzuki M., T-independent antibody production in nude mice immunized with a rodent malaria parasite (Plasmodium berghei), Proc. third international workshop on nude mice, pp. 91-101, (1982)

[8]

Croitoru K., Ernst P.B., Leukocytes in the intestinal epithelium: an unusual immunological compartment revisited, Reg Immunol, 4, (1992)

[9]

Nishimura T., Togashi Y., Wakamiya N., Hashimoto Y., Yagita H., Okumura K., Habu S., T cell receptor-independent cell-mediated cytotoxicity by nude mouse lymphokine-activated killer cells, Jpn J Cancer Res, 82, (1991)

[10]

Pritchard H., Micklem H.S., Haemopoietic stem cells and progenitors of functional Tlymphocytes in the bone marrow of ’nude’ mice, Clin Exper hnmunol, 14, (1973)

← 1 2 3 →