Metronomic treatment in immunocompetent preclinical GL261 glioblastoma: effects of cyclophosphamide and temozolomide

Glioblastoma (GBM) causes poor survival in patients even when applying aggressive treatment. Temozolomide (TMZ) is the standard chemotherapeutic choice for GBM treatment, but resistance always ensues. In previous years, efforts have focused on new therapeutic regimens with conventional drugs to activate immune responses that may enhance tumor regression and prevent regrowth, for example the “metronomic” approaches. In metronomic scheduling studies, cyclophosphamide (CPA) in GL261 GBM growing subcutaneously in C57BL/6 mice was shown not only to activate antitumor CD8⁺ T‐cell response, but also to induce long‐term specific T‐cell tumor memory. Accordingly, we have evaluated whether metronomic CPA or TMZ administration could increase survival in orthotopic GL261 in C57BL/6 mice, an immunocompetent model. Longitudinal in vivo studies with CPA (140 mg/kg) or TMZ (range 140–240 mg/kg) metronomic administration (every 6 days) were performed in tumor‐bearing mice. Tumor evolution was monitored at 7 T with MRI (T₂‐weighted, diffusion‐weighted imaging) and MRSI‐based nosological images of response to therapy. Obtained results demonstrated that both treatments resulted in increased survival (38.6 ± 21.0 days, n = 30) compared with control (19.4 ± 2.4 days, n = 18). Best results were obtained with 140 mg/kg TMZ (treated, 44.9 ± 29.0 days, n = 12, versus control, 19.3 ± 2.3 days, n = 12), achieving a longer survival rate than previous group work using three cycles of TMZ therapy at 60 mg/kg (33.9 ± 11.7 days, n = 38). Additional interesting findings were, first, clear edema appearance during chemotherapeutic treatment, second, the ability to apply the semi‐supervised source analysis previously developed in our group for non‐invasive TMZ therapy response monitoring to detect CPA‐induced response, and third, the necropsy findings in mice cured from GBM after high TMZ cumulative dosage (980–1400 mg/kg), which demonstrated lymphoma incidence. In summary, every 6 day administration schedule of TMZ or CPA improves survival in orthotopic GL261 GBM with respect to controls or non‐metronomic therapy, in partial agreement with previous work on subcutaneous GL261.     

HIV Prevalence,Knowledge, Attitudes,and Practices Among Polydrug Users in Brazil: A Biological Survey Using Respondent Driven Sampling

Brazil has a concentrated HIV epidemic among key populations. In 2009, the Ministry of Health conducted a survey in 10 Brazilian cities aiming to estimate HIV prevalence, knowledge, and associated risk behaviors of polysubstance users (PSU). Using Respondent Driven Sampling (RDS), 3449 PSU were recruited, answered an Audio-Computer Self Assisted Interview (ACASI) and were tested for HIV and syphilis. Analyses were weighted by individual’s social network size generated on RDSAT. Pooled HIV prevalence was 5.8% but varied across cities. Most PSU were male, non-white, without income, unemployed, with low levels of education. Overall, 12.0% used injectable drugs, 48.7% had sex with occasional partners and 46.4% engaged in commercial sex. A majority received free condoms (71.4%) but 76.7% exhibited inconsistent condom use. Findings can support policies aiming to improve health care and preventive interventions tailored to this population that remains at high risk of acquiring and transmitting HIV/STI in multiple scenarios.     

Norwegian scabies mimicking rupioid psoriasis

Norwegian scabies is a highly contagious skin infestation caused by an ectoparasite, Scarcoptes scabiei var. Hominis, which mainly affects immunosuppressed individuals. Clinically, it may simulate various dermatoses such as psoriasis, Darier''s disease, seborrheic dermatitis, among others. This is a case report of a 33-year-old woman, immunocompetent, diagnosed with generalized anxiety disorder (cancer phobia), who had erythematous, well-defined plaques, covered with rupioid crusts, on her neck, axillary folds, breast, periumbilical region, groin area, besides upper back and elbows, mimicking an extremely rare variant of psoriasis, denominated rupioid psoriasis.