Multidrug resistant prostate cancer cell lines DU 0.03 and PC 0.03 were established from the parental prostate cancer cell lines DU145 and PC-3 respectively by stepwise selection in doxorubicin (DOX) from 0.001 to 0.03 m mg/ml. As cells adapted to each concentration of DOX. the drug concentration was increased by 0.001 m mg/ml. The chemosensitivity of each line was determined by growth inhibition assay. The DU 0.03 and PC 0.03 lines exhibit a 5 ± 10-fold and 1.3 ± 2.8-fold increase in resistance to anthracyclines, vinblastine (VLB) and mitozantrone (Mito), respectively. Verapamil (5 m mM) partially reversed the resistance to the anthracycline and completely reversed the resistance to VLB and Mito. Drug kinetic studies measured by intracellular accumulation of 3 H-daunorubicin demonstrated a 3 fold decrease in the level of intracellular 3 H-daunorubicin in the PC 0.03 and DU 0.03 resistant lines compared with their respective parental line. This effect was partially reversed by 5 m mM verapamil. The expression of MDR1 and MRP genes was analysed by Northern blotting and RT-PCR. P-glycoprotein (Pgp) and MRP protein were tested by immunocytochemistry staining using the monoclonal antibodies J-SB1. C219 and MRK16 (Pgp) and MRPm6 and MRPr1 (MRP). Neither Northern blot analysis nor the more sensitive RT-PCR demonstrated detectable MDR1 transcripts in any of the prostate cancer cell lines and the three Pgp monoclonal antibodies failed to reveal expression of Pgp.A 2 ± 4-fold increase in MRP1 mRNA levels in the drug resistant DU 0.03 and PC 0.03 lines were demonstrated by both Northern blotting and RT-PCR consistent with the ®ndings observed after staining by the two speci®c monoclonal antibodies, MRPm6 and MRPr1. Southern blot analysis demonstrated a 2-fold increase in the MRP1 gene copy number in the PC 0.03 line but not in the DU 0.03 line, suggesting that the overexpression of the MRP gene was regulated at the level of transcription in the latter line. We conclude that MRP1 not MDR1 overexpression. contributes to acquired drug resistance in these two prostate cancer cell lines. Prostate Cancer and Prostatic Diseases (2000) 3, 66±75.

In recent years, Candida infections have been increasing significantly. This study was to investigate the distribution and fluconazole susceptibility of such infections. Totally, 3,056 clinical isolates were analysed, C. albicans was the most prevalent species from respiratory and vaginal specimens. However, non-albicans species constituted the majority of isolates from blood, urine, intensive care unit (ICU), organ transplant and burned patients. Similarly, Candida spp. from different specimens and clinical services had different degrees of susceptibility to fluconazole. Isolates from vagina and burned patients had the highest resistance rate, while all of the isolates from ascites and dermatological services were susceptible to fluconazole.

Hypothalamic-pituitary functions in 26 cases of Turner syndrome were assessed with a combined stimulation test. The results showed that the peak GH levels of 12 cases were less than 10 micrograms/L; 3 patients were demonstrated as having an even TSH response, while another one with a delayed TSH peak, and other 4 had high basal values and consistent exaggerated TSH responses to TRH; all patients showed increased basal and peak LH and FSH levels but 5, whose LH and FSH secretion patterns were similar to normal. 12 cases have been treated with individualized protocols and followed up for 12 months or more, of them the growth velocity all increased, especially those with hypothyroidism or with a BA less than 13. It is suggested that multiple functions of hypothalamic-pituitary axis in Turner patients be evaluated as early as possible, in order that proper treatment could be adopted and their growth and development improved.