Development of the Palliative Care Law and Policy GPS to Assess National Policies in Palliative Care.

State policy-making to address disparities in access to and quality of palliative care is increasing. Yet, there is no mechanism to systematically assess palliative care policies nationally. We describe the development of the Palliative Care Law and Policy GPS by the Center to Advance Palliative Care and the Yale Solomon Center for Health Law and Policy.

An ATM/Chk2-mediated DNA damage-responsive signaling pathway suppresses Epstein-Barr virus transformation of primary human B cells.

Epstein-Barr virus (EBV), an oncogenic herpesvirus that causes human malignancies, infects and immortalizes primary human B cells in vitro into indefinitely proliferating lymphoblastoid cell lines, which represent a model for EBV-induced tumorigenesis. The immortalization efficiency is very low, suggesting that an innate tumor suppressor mechanism is operative. We identify the DNA damage response (DDR) as a major component of the underlying tumor suppressor mechanism.

CLN3p impacts galactosylceramide transport, raft morphology, and lipid content.

Juvenile neuronal ceroid lipofuscinosis (JNCL) belongs to the neuronal ceroid lipofuscinoses characterized by blindness/seizures/motor/cognitive decline and early death. JNCL is caused by CLN3 gene mutations that negatively modulate cell growth/apoptosis. CLN3 protein (CLN3p) localizes to Golgi/Rab4-/Rab11-positive endosomes and lipid rafts, and harbors a galactosylceramide (GalCer) lipid raft-binding domain.

Ras mediates radioresistance through both phosphatidylinositol 3-kinase-dependent and Raf-dependent but mitogen-activated protein kinase/extracellular signal-regulated kinase kinase-independent signaling pathways.

Cells transformed by the oncogenic small GTPase, Ras, display a radioresistant phenotype in response to ionizing radiation (IR). To determine the mechanisms by which Ras mediates radioresistance in epithelial cells, we assessed the importance of three major survival pathways that can be activated by Ras [phosphatidylinositol 3-kinase (PI3-K)>Akt, nuclear factor kappaB (NF-kappaB), and Raf>mitogen-activated protein kinase/extracellular signal-regulated kinase kinase (MEK)>extracellular signal-regulated kinase] as necessary or sufficient for Ras-mediated radioresistance in matched pairs of RIE-1 rat intestinal epithelial cells expressing oncogenic Ras or empty vector (RIE-Ras and RIE-vector). Inhibiting PI3-K with LY294002 sensitized RIE-1 cells to IR in a dose-dependent manner, indicating that PI3-K is necessary for radioresistance, whereas inhibition of NF-kappaB with the super-repressor IkappaBalpha had little effect on survival.

R-Ras C-terminal sequences are sufficient to confer R-Ras specificity to H-Ras.

Activated versions of the similar GTPases, H-Ras and R-Ras, have differing effects on biological phenotypes: Activated H-Ras strongly transforms many fibroblast cell lines causing dramatic changes in cell shape and cytoskeletal organization. In contrast, R-Ras transforms fewer cell lines and the transformed cells display only some of the morphological changes associated with H-Ras transformation. H-Ras cells can survive in the absence of serum whereas R-Ras cells seem to die by an apoptotic-like mechanism in response to removal of serum.