Broad targeting of resistance to apoptosis in cancer

Apoptosis or programmed cell death is natural way of removing aged cells from the body. Most of the anti-cancer therapies trigger apoptosis induction and related cell death networks to eliminate malignant cells. However, in cancer, de-regulated apoptotic signaling, particularly the activation of an anti-apoptotic systems, allows cancer cells to escape this program leading to uncontrolled proliferation resulting in tumor survival, therapeutic resistance and recurrence of cancer. This resistance is a complicated phenomenon that emanates from the interactions of various molecules and signaling pathways. In this comprehensive review we discuss the various factors contributing to apoptosis resistance in cancers. The key resistance targets that are discussed include (1) Bcl-2 and Mcl-1 proteins; (2) autophagy processes; (3) necrosis and necroptosis; (4) heat shock protein signaling; (5) the proteasome pathway; (6) epigenetic mechanisms; and (7) aberrant nuclear export signaling. The shortcomings of current therapeutic modalities are highlighted and a broad spectrum strategy using approaches including (a) gossypol; (b) epigallocatechin-3-gallate; (c) UMI-77 (d) triptolide and (e) selinexor that can be used to overcome cell death resistance is presented. This review provides a roadmap for the design of successful anti-cancer strategies that overcome resistance to apoptosis for better therapeutic outcome in patients with cancer

Planum temporale asymmetry in developmental dyslexia: Revisiting an old question

Among the various asymmetrical structures of the human brain, the planum temporale, an anatomical region associated with a variety of auditory and language-related processes, has received particular attention. While its surface area has been shown to be greater in the left hemisphere compared to the right in about two-thirds of the general population, altered patterns of asymmetry were revealed by post mortem analyses in individuals with developmental dyslexia. These findings have been inconsistently replicated in magnetic resonance imaging studies of this disorder. In this report, we attempt to resolve past inconsistencies by analyzing the T1-weighted MR images of 81 children (mean age: 11 years, sd: 17 months), including 46 control (25 boys) and 35 dyslexic children (20 boys). We manually outlined Heschl's gyri, the planum temporale and the posterior rami of the Sylvian fissure on participants' brain images, using the same anatomical criteria as in post mortem studies. Results revealed an altered pattern of asymmetry of the planum temporale surface area in dyslexic boys only, with a greater proportion of rightward asymmetrical cases among dyslexic boys compared to control boys. Additionally, analyses of cortical thickness showed no asymmetry differences between groups for any of the regions of interest. Finally, a greater number of Heschl's gyrus full duplications emerged for the right hemisphere of dyslexic boys compared to controls. The present findings confirm and extend early post mortem observations. They also stress the importance of taking gender into account in studies of developmental dyslexia. Hum Brain Mapp 35:5717-5735, 2014. © 2014 Wiley Periodicals, Inc

Combined Bacterial Meningitis and Infective Endocarditis: When Should We Search for the Other When Either One is Diagnosed?

Auteurs groupes collaboratifs AEPEI study group & the COMBAT study groupInternational audienc