Pre-clinical activity of taxol in non-seminomatous germ cell tumor cell lines and nude mouse xenografts

作者: T.A. Dunn , H.J. Schmoll , V. Grüunwald , J. Casper , C. Bokemeyer

DOI: 10.1023/A:1005852521656

关键词:

摘要: Taxol (Paclitaxel) is a novel anti-cancer drug which has shown excellent clinical activity in variety of solid tumors, particularly metastatic breast and ovarian cancer. 70-80% patients with non-seminomatous germ cell tumor (NSGCT) attain disease free status standard cisplatin-based combination chemotherapy but the emergence resistance still prevents small proportion these from achieving long-term remission. Here we report results pre-clinical studies investigating whether taxol exhibits cross-resistance to cisplatin or ifosfamide human NSGCT lines refractory xenograft model NSGCT. Following 96h exposure 5-day sulphohodamine B (SRB) vitro assay, demonstrated potent cytotoxicity were sensitive (577 LM, H32, H12.1; mean IC50s 1.5-3.0 nM) those acquired intrinsic (H12DDP, H23; 2.5 nM). Compared line, H12.1, IC50 values increased line 1777NRp Cl-A intermediate level (4.7 nM; p > 0.05) significantly elevated 1411HP, high (6.9 0.01). The latter 2 may represent models corresponding relapsing after high-dose platinum-based who seem be resistant therapy. H32 H12DDP approximately 100 fold lower following times exceeding 24 hours compared short (1-6h). Dose dependent anti-tumor was observed cisplatin-refractory (H23), significant at dose 15 mg/kg/d injected intra-venously on days 1 through 5. this study are accordance most recent data showed that useful relapsed testicular cancer, being 25% patients, poor previously treated Further research, especially using such as 1411HP Cl-A, combinations other regimens required enable successful treatment tumors.

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