Leptin-signaling inhibition results in efficient anti-tumor activity in estrogen receptor positive or negative breast cancer

Introduction: We have shown previously that treatment with pegylated leptin peptide receptor antagonist 2 (PEG-LPrA2) reduced the expression of vascular endothelial growth factor (VEGF), vascular endothelial growth factor receptor type 2 (VEGFR2) and growth of 4T1-breast cancer (BC) in syngeneic mice. In this investigation, PEG-LPrA2 was used to evaluate whether the inhibition of leptin signaling has differential impact on the expression of pro-angiogenic and pro-proliferative molecules and growth of human estrogen receptor-positive (ER+) and estrogen receptor-negative (ER-) BC xenografts hosted by immunodeficient mice. Methods: To test the contribution of leptin signaling to BC growth and expression of leptin-targeted molecules, PEG-LPrA2 treatment was applied to severe immunodeficient mice hosting established ER+ (MCF-7 cells; ovariectomized/supplemented with estradiol) and ER- (MDA-MB231 cells) BC xenografts. To further assess leptin and PEG-LPrA2 effects on ER+ and ER- BC, the expression of VEGF and VEGFR2 (protein and mRNA) was investigated in cell cultures. Results: PEG-LPrA2 more effectively reduced the growth of ER+ (>40-fold) than ER- BC (twofold) and expression of pro-angiogenic (VEGF/VEGFR2, leptin/leptin receptor OB-R, and IL-1 receptor type I) and pro-proliferative molecules (proliferating cell nuclear antigen and cyclin D1) in ER+ than in ER- BC. Mouse tumor stroma in ER+ BC expressed high levels of VEGF and leptin that was induced by leptin signaling. Leptin upregulated the transcriptional expression of VEGF/VEGFR2 in MCF-7 and MDA-MB231 cells. Conclusions: These results suggest that leptin signaling plays an important role in the growth of both ER+ and ER- BC that is associated with the leptin regulation of pro-angiogenic and pro-proliferative molecules. These data provide support for the potential use of leptin-signaling inhibition as a novel treatment for ER+ and ER- BC

Efficacy of pyrethroid insecticides against domestic and peridomestic populations of Triatoma pallidipennis and Triatoma barberi (Reduviidae:Triatominae) vectors of Chagas' disease in Mexico.

A single village control trial for Triatoma pallidipennis and T. barberi was conducted using three synthetic pyrethroids (bifenthrin, cyfluthrin, and deltamethrin), evaluated as residual treatments in separate sectors, with complete coverage indoors and in peridomiciliary areas. Spray intervention was preceded by a preintervention entomological evaluation and household survey, followed by four postintervention evaluations at 1, 3, 6, and 12 mo of > 96% of houses. Overall preintervention adjusted infestation index was 38%, 17% of which represented intradomicile infestation. Dose verification using high-performance liquid chromatography (HPLC) demonstrated correct spray doses for all but deltamethrin treatments. There was between a 6- and 13-fold decrease in intradomicile live bug infestation for cyfluthrin- and bifenthrin-treated areas, resulting at 1 mo in 0 and 0.6% infestation, respectively. Intradomicile infestation recovered somewhat, terminating at 20 and 50% of preintervention levels at 12 mo, respectively, while peridomicile infestation recovered preintervention levels within 3-6 mo. Households with persistent live peridomiciliary infestation had 1.9 times the risk of having a persistent intradomiciliary infestation, while 80% of peridomicile infestations for both triatomine species were in houses not having a previous infestation. New or reinfestation of households did not occur consistent with a sylvan source, and unconstructed lots were not a significant source of bugs. Houses with persistent peridomicile infestation did represent a significant risk for surrounding uninfested houses by cluster analysis (P < 0.05). Along with the increased prevalence of T. cruzi infection after intervention, the data indicate that a sylvan reservoir source, probably peridomicile small rodent nests, represent the major risk factor for persistent and new infestations