Retinoblastoma Loss Modulates DNA Damage Response Favoring Tumor Progression

Senescence is one of the main barriers against tumor progression. Oncogenic signals in primary cells result in oncogene-induced senescence (OIS), crucial for protection against cancer development. It has been described in premalignant lesions that OIS requires DNA damage response (DDR) activation, safeguard of the integrity of the genome. Here we demonstrate how the cellular mechanisms involved in oncogenic transformation in a model of glioma uncouple OIS and DDR. We use this tumor type as a paradigm of oncogenic transformation. In human gliomas most of the genetic alterations that have been previously identified result in abnormal activation of cell growth signaling pathways and deregulation of cell cycle, features recapitulated in our model by oncogenic Ras expression and retinoblastoma (Rb) inactivation respectively. In this scenario, the absence of pRb confers a proliferative advantage and activates DDR to a greater extent in a DNA lesion-independent fashion than cells that express only HRasV12. Moreover, Rb loss inactivates the stress kinase DDR-associated p38MAPK by specific Wip1-dependent dephosphorylation. Thus, Rb loss acts as a switch mediating the transition between premalignant lesions and cancer through DDR modulation. These findings may have important implications for the understanding the biology of gliomas and anticipate a new target, Wip1 phosphatase, for novel therapeutic strategies

Sulfated Polysaccharide, Curdlan Sulfate, Efficiently Prevents Entry/Fusion and Restricts Antibody-Dependent Enhancement of Dengue Virus Infection In Vitro: A Possible Candidate for Clinical Application

10.1371/journal.pntd.0002188PLoS Neglected Tropical Diseases74

ICAR: endoscopic skull‐base surgery

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Medical Rehabilitation in Natural Disasters in the Asia-Pacific Region: The Way Forward

The Asia-Pacific is the most disaster-prone region in the world, with over 40% of the world's disasters occurring here in the past decade. This region has geo-political and socio-economic diversity which increases vulnerability to natural and other disasters. With increasing frequency of natural disasters, there is greater focus on the role of rehabilitation in disaster response and management. Early rehabilitation and preventative care in disaster survivors has the potential to minimize complications, optimize early recovery and reduce the economic burden. This article presents an overview of medical rehabilitation status in natural disaster settings in the Asia-Pacific region. It highlights the role of medical rehabilitation in disaster response and management, potential challenges faced by the countries in the region and key initial perspectives which need consideration for future disaster planning. Rehabilitation and long-term management of disaster survivors requires diverse forms of multi-sectorial partnerships, strategic collaboration, provision of service development, research and knowledge transfer