HER Family Receptors are Important Theranostic Biomarkers for Cervical Cancer: Blocking Glucose Metabolism Enhances the Therapeutic Effect of HER Inhibitors

Persistent HPV infection alone is not sufficient for cervical cancer development, which requires additional molecular alterations for tumor progression and metastasis ultimately leading to a lethal disease. In this study, we performed a comprehensive analysis of HER family receptor alterations in cervical adenocarcinoma. We detected overexpression of HER protein, mainly HER2, which was an independent prognostic marker for these patients. By using in vitro and in vivo approaches, we provided evidence that HER inhibitors, allitinib and lapatinib, were effective in reducing cervical cancer aggressiveness. Furthermore, combination of these drugs with glucose uptake blockers could overcome the putative HIF1-a-mediated resistance to HER-targeted therapies. Thus, we propose that the use of HER inhibitors in association with glycolysis blockers can be a potentially effective treatment option for HER-positive cervical cancer patients.FINEP (MCTI/FINEP/MS/SCTIE/DECIT-BIOPLAT (1302/13), Brazil and co-funded by the project “ON.2 SR&TD Integrated Program (NORTE-07-0124-FEDER-000017)” co-funded by Programa Operacional Regional do Norte (ON.2- O Novo Norte), Quadro de Referência Estratégico Nacional (QREN), through Fundo Europeu de Desenvolvimento Regional (FEDER). OM is recipient of a post-doc fellowship (SFRH/BPD/108351/2015) from Fundação para a Ciência e Tecnologia (FCT), Portugal. FC is recipient of a master fellowship (2014/03684-0) from Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP). VMG is recipient from a PhD fellowship (SFRH/BD/51997/2012) from Fundação para a Ciência e Tecnologia (FCT), Portugalinfo:eu-repo/semantics/publishedVersio

The influence of behavioral enrichment on dry food consumption by the black tufted-ear marmoset, Callithrix penicillata (Mammalia: Callithricidae): a pilot study

Stereotyped behaviors in captive primates are often caused by unsuitable conditions. Environmental enrichment has been used to reduce these behaviors, and also to increase the frequency of behaviors appropriate to the species. In this pilot study we evaluated whether behavioral enrichment influences food intake by the black tufted-ear marmoset, Callithrix penicillata (É. Geoffroy Saint-Hilaire, 1812), by calculating energy maintenance requirements. We evaluated 16 individually housed, healthy adult black tufted-ear marmosets, randomly divided into two treatment groups, one with behavioral enrichment and one without. The enrichment techniques included structural aspects, such as placing fixed and mobile objects in the cage and supplying dry foods in an enriched form, in order to stimulate cognition. Based on the metabolic weight of the animals, we calculated the energy requirements for their maintenance. The animals that received behavioral enrichment consumed more food than those that did not. We also observed that the animals that did not receive enrichment consumed 9.85% less food than had been calculated for energy maintenance requirements, while the animals that received enrichment consumed 24.97% more food than had been calculated. Results indicate that the use of behavioral enrichment items raised the energy requirements of the black tufted-ear marmoset and, therefore, the consumption of dry food, suggesting that environmental enrichment plays a role in stimulating food consumption. This conclusion should alert scientists, technicians and primatologists to the importance of controlling body weight of marmosets when introducing environmental enrichment to avoid overfeeding and obesity. To verify this conclusion, a study is needed with a longer time frame and more parameters, such as behavior observation and body weight