Steroid Sulfatase Inhibitor Reduces Proliferation of Ishikawa Endometrial Cancer Cells in Co-Culture Systems

Objectives: Estrogens significantly contribute toward the growth and development of endometrial cancers. Two principal pathways have been implicated in the final steps of estrogen synthesis: the steroid sulfatase (STS) and aromatase pathways. In this study, we aimed to evaluate the possible effects of tumor-stromal interactions on local estrogen biosynthesis in endometrial cancer. We also assessed the biological effects of inhibitors of steroid sulfatase and aromatase in the co-culture system compared with usual monocultures. Methods/Materials: We isolated stromal cells from endometrial cancer patients to examine local biosynthesis of estrogens and tumor-stromal interactions. Next we examined the effects of steroid sulfatase inhibitor and aromatase inhibitor in monoculture of endometrial cancer cell line (Ishikawa) and in a co-culture system involving an Ishikawa cells and stromal cells. Results: Estrogen receptor and steroid sulfatase mRNA levels in cancer cells were significantly higher in the co-cultures compared with the monocultures of endometrial cancer cells. Estradiol and androstenediol concentrations were also significantly higher in the co-cultured cells. Proliferation of the cancer cells was significantly increased through the steroid sulfatase pathway, which metabolizes androgens, estrone sulfate, and estradiol sulfate as its substrates. However, its proliferation was significantly decreased by the treatment of steroid sulfatase or aromatase inhibitors. The significant growth inhibition by the steroid sulfatase and aromatase inhibitors were also observed in the co-culture system. Conclusions: We evaluated the effects of STS inhibitor and aromatase inhibitors on the proliferation of estrogen-dependent endometrial cancer cells. Considering that intratumoral estrogen metabolism plays an important role, our co-culture systems provide an environment similar to that of the tumor in living patients in terms of metabolism and synthesis of intratumoral estrogens. The results of this study may aid in achieving improved clinical responses from patients treated with STS inhibitors.

Prescription trends in children with pervasive developmental disorders:a claims data-based study in Japan

Background:The only drug approved for pervasive developmental disorders(PDD)in Japan is pimozide.Several psychotropic drugs are also prescribed for offlabel use in Japan,but details regarding their prescription and use are largely unknown.The purpose of this study was to clarify the use of drug treatment in Japanese children with PDD.Methods:Data were extracted from claims data from the Japan Medical Data Center for children younger than 18 years of age who were newly diagnosed with PDD(International Classification of Diseases version 10 codes:F84)from 2005 to 2010(total of 3276 patients as of 2010).The prescription rates were presented as the percentage of PDD patients who were prescribed each drug.Results:Prior to 2010,the prescription rates for atypical antipsychotics,other antipsychotics,psychostimulants,all other central nervous system drugs,anticovnvulsants,non-barbiturates,and Parkinson’s disease/syndrome drugs significantly increased among the Anatomical Therapeutic Chemical classifications defined as the“nervous system”(trend P≤0.02).The prescription rate for risperidone consistently increased,reaching 6.9%in 2010(trend P<0.0001),the highest rate of the surveyed drugs among the antipsychotics.The prescription rate for aripiprazole also increased(trend P<0.0001),reaching 1.9%in 2010.The prescription rate for pimozide showed no annual changes,with a low rate of 0.4%in 2010.Conclusion:Compared with pimozide,the prescription rates for risperidone,aripiprazole and other psychotropic drugs have increased.Because safety data for these drugs in Japanese children are sparse,there is a need for future safety evaluations of these drugs in Japanese children.