Tumor-suppressive effects of MBP-1 in non-small cell lung cancer cells

Lung cancer is the leading cause of cancer death among both men and women. Only approximately 15% of people diagnosed with non-small cell lung cancer (NSCLC) survive this disease beyond 5 years. Thus, novel therapeutic strategies are urgently needed to improve the clinical management of this devastating disease. We have previously shown the antiproliferative effect of MBP-1 on several human cancer cells. In this study, we have examined the potential of MBP-1 as a gene therapeutic candidate in regression of non-small cell lung tumor growth. We have observed that exogenous expression of MBP-1 in NSCLC cells (H1299) induces massive cell death. To determine the gene therapeutic potential of MBP-1, replication-deficient recombinant adenovirus expressing MBP-1 was given intratumorally in human lung cancer xenografts in nude mice. Our results showed a significant regression of lung tumor growth and prolonged survival on treatment with MBP-1 compared with the control groups (saline or dl312). Subsequently, the mechanism of MBP-1-mediated H1299 cell death was investigated. Our results suggested that MBP-1 induced poly(ADP-ribose) polymerase cleavage in H1299 cells; however, treatment with pan-caspase inhibitor did not protect against MBP-1-induced cell death. Cells transduced with MBP-1 displayed early plasma membrane permeability, mitochondrial damage without cytochrome c release, and extensive cytoplasmic vacuolation, yielding a morphotype that is typical of necrosis. Taken together, this study suggests that MBP-1 expression induces a novel form of necrosis-like cell death and MBP-1 could be a potential gene therapeutic candidate against non-small cell lung tumor growth.     

Medical abortion in late second trimester--a comparative study with misoprostol through vaginal versus oral followed by vaginal route

A randomised controlled trial was conducted to compare the relative efficacies of two regimens: Misoprostol given only vaginally or orally followed by vaginal administration of the same drug, for second trimester abortion. Multiparous women with a pregnancy of 16 to 20 weeks with no contra-indications to the drug were selected. They were randomly allocated into two groups. Patients in the first group, the 'only vaginal misoprostol' group (n = 30), were given misoprostol 400 microg 6 hourly only through vaginal route up to a maximum of 4 such doses. Women in the other group, the 'oral plus vaginal misoprostol' group (n = 24), received 400 microg of the drug at intervals of 12 hours for 2 doses, followed by 400 microg 6 hourly per vaginum up to a maximum of 4 such. Ten units of oxytocin was started in all cases when os was 4 cm dilated. Complete expulsion was 83.33% with an average time of 13.28 hours in the only vaginal misoprostol group. Complete expulsion occurred in 87.5% of women receiving oral followed by vaginal misoprostol with an average time of 8.93 +/- 0.01 hours from the first vaginal dose (p<0.05). More importantly, 66.67% women in second group delivered within 10 hours of the vaginal dose. Complete expulsion was defined in those cases where no check curettage was needed. Side-effects were not significant. This implies that misoprostol given by the vaginal route following oral priming doses had a higher success rate and a potential for a reduced hospital stay and higher bed turn-over rate.