No abstract

Treatment with indinavir has been shown to result in marked decreases in viral load and increases in CD4 cell counts in HIV-infected individuals. A randomized double-blind study to evaluate the efficacy of indinavir alone (800 mg q8h), zidovidine alone (200 mg q8h) or the combination was performed to evaluate progression to AIDS. 996 antiretroviral therapy-naive patients with CD4 cell counts of 50-250/mm3 were allocated to treatment. During the trial the protocol was amended to add lamivudine to the zidovudine-containing arms. The primary endpoint was time to development of an AIDS-defining illness or death. The study was terminated after a protocol-defined interim analysis demonstrated highly significant reductions in progression to a clinical event in the indinavir-containing arms, compared to the zidovudine arm (p<0. 0001). Over a median follow-up of 52 weeks (up to 99 weeks), percent reductions in hazards for the indinavir plus zidovudine and indinavir groups compared to the zidovudine group were 70% and 61%, respectively. Significant reductions in HIV RNA and increases in CD4 cell counts were also seen in the indinavir-containing groups compared to the zidovudine group. Improvement in both CD4 cell count and HIV RNA were associated with reduced risk of disease progression. All three regimens were generally well tolerated.

No abstract

Breast cancer is the most prevalent type of tumor and a major leading cause of cancer mortality. Triple-negative breast cancer (TNBC) has the worst prognosis due to its malignant characteristics and the absence of efficacious treatments. Crotoxin, a protein in Crotalus genus snake venom, has proven antitumor activity against aggressive solid tumors, but marked toxicity in humans. Crotoxin B-derived peptides were synthesized and evaluated in vitro for their antitumor activity, which resulted in the discovery of 3-NAntC. 3-NAntC (1µg/mL) treatment for 72 hours decreased the MDA-MB-231 cells viability to 49.0%±17.5% (p < 0.0001), while the same condition resulted in the viability of HMEC cells at 98.2%±13.8%. 3-NAntC exhibited higher antitumoral activity in vitro than cisplatin and similar effect of doxorubicin. 3-NAntC reduced MDA-MB-231 cell proliferation and caused a G2/M arrest. 3-NAntC primarily induced apoptosis, with a lower necrosis occurrence compared with doxorubicin. 3-NAntC caused a low LDH release, and its cytotoxicity was not impaired by the autophagy inhibitor 3-MA. In zebrafish in vivo model, 3-NAntC was very well tolerated, showing no lethal effect and a low malformation rate at ≤ 75mg/mL. 3-NAntC is a novel synthetic peptide with promising antitumor effects in vitro against TNBC cells and with low toxicity in vivo.