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Glioblastomas are resistant to many kinds of treatment, including chemotherapy, radiation and other adjuvant therapies. As2O3 reportedly induces ROS generation in cells, suggesting it may be able to induce telomerase suppression and telomere dysfunction in glioblastoma cells. We show here that As2O3 induces ROS generation as well as telomerase phosphorylation in U87, U251, SHG4 and C6 glioma cells. It also induces translocation of telomerase from the nucleus to the cytoplasm, thereby decreasing total telomerase activity. These effects of As2O3 trigger an extensive DNA damage response at the telomere, which includes up-regulation of ATM, ATR, 53BP1, γ-H2AX and Mer11, in parallel with telomere fusion and 3′-overhang degradation. This ultimately results in induction of p53- and p21-mediated cell apoptosis, G2/M cell cycle arrest and cellular senescence. These results provide new insight into the antitumor effects of As2O3 and can perhaps contribute to solving the problem of glioblastoma treatment resistance.

Background Knowledge on the occurrence of erectile dysfunction (ED) and timely ovulatory intercourse failure (TOIF) in Chinese men of infertile couples is limited. Aim To obtain representative estimates of ED and TOIF in Chinese men of infertile couples and to analyze potential risk factors associated with ED. Methods 4,299 Chinese men of infertile couples with an average age of 32.85 ± 5.98 years were surveyed using the 5-item International Index of Erectile Function (IIEF-5) questionnaire for their ED occurrence. Multiple logistic regression analysis was used to disclose risk factors associated with ED. Outcomes The occurrence of ED was 57.8% and that of TOIF was up to 26.2% in Chinese men of infertile couples. Results Based on IIEF-5 criteria, 34.9% of men had mild ED and only 2.6% had severe ED. Secondary infertility, infertility with known causes, and chronic prostatitis were significant risk factors associated with ED. TOIF was significantly higher (23.3%) in men of infertile couples with ED than in those without ED (8.6%), indicating that TOIF is likely a contributing factor to male infertility. Clinical Implications Understanding the occurrence and types of ED and TOIF in men of infertile couples and their associated risk factors will help physicians treat clinical cases of male infertility more effectively. Strengths and Limitations Large numbers of infertile outpatients from multiple hospital clinics across the country were included in this study. The concept of TOIF was raised for the 1st time and studied preliminarily in Chinese men of infertile couples. The lack of participants' psychological status, a control group of men of fertile couples, and measurement of testosterone levels was a limitation in this clinic-based study. Conclusion The occurrence of ED was higher in Chinese men of infertile couples than in the general Chinese male population.