Fichtner I, Reszka R, Goan S R, Naundorf H
Max-Delbrück-Center of Molecular Medicine, Berlin, Germany.
Med Oncol. 1994;11(3-4):111-9. doi: 10.1007/BF02999858.
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.(ABSTRACT TRUNCATED AT 250 WORDS)
卡铂脂质体（CPL）已被证明对免疫活性小鼠的造血功能具有强烈的刺激活性。由于我们有兴趣研究这种药理学特性以及包封的细胞抑制剂可能预期的任何抗肿瘤作用，我们使用了一组移植到裸鼠体内的六种人类乳腺癌。与游离药物相比并结合使用，研究了囊泡的抗肿瘤活性以及造血作用。将卡铂包封到反相蒸发囊泡（REV）中，分别以75 mg kg-1的单剂量腹腔注射到无肿瘤和患有乳腺癌的动物体内。在裸鼠单次应用CPL后，在至少28天的时间内，可以观察到白细胞数量显著增加至正常水平的约三倍。这种升高是由于循环粒细胞和淋巴细胞均增加所致。外周效应伴随着脾脏细胞数量的相对减少，而骨髓细胞数量几乎未受影响。在SCID小鼠中未检测到对循环血细胞的影响。然而，注意到CPL对这种免疫缺陷小鼠品系具有相当高的毒性。在所使用的乳腺癌组中，游离卡铂和CPL表现出不同的治疗效率模式。在测试的五个肿瘤模型中的四个中，游离药物与脂质体药物的组合显示出对肿瘤生长的显著抑制，同时有效地防止了药物诱导的白细胞减少。（摘要截断于250字）
