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Rallon N.I.,Charles III University of Madrid | Restrepo C.,Charles III University of Madrid | Naggie S.,Duke Clinical Research Institute | Lopez M.,Charles III University of Madrid | And 5 more authors.
AIDS | Year: 2011

The critical role of interleukin-28B (IL28B)/interferon-λ3 (IFN-λ3) polymorphisms on the susceptibility to hepatitis C virus infection and the response to peginterferon-ribavirin therapy has encouraged exploration of similar effects on other viruses. Given that IFN-λ mediates anti-HIV-1 activity, the protective role of IL28B polymorphisms was examined in 29 seronegative individuals at risk for HIV-infection and in 68 HIV-positive carriers with and without rapid progression of immunodeficiency. No protective role of IL28B polymorphism was found examining both HIV-disease progression and HIV-protection. © 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins. Source


Chen Y.,National Taiwan University | Kung H.-N.,National Taiwan University | Kung H.-N.,Institute for Genome science and Policy | Chen C.-H.,National Taiwan University | And 4 more authors.
FEBS Letters | Year: 2011

An acidic microenvironment induces disruption of adherens junctions (AJs) of hepatoma cells. This study investigated the impact of an acidic extracellular pH (pHe) on p120-catenin (p120-ctn) serine phosphorylation. pH 6.6 treatment increased intracellular calcium levels, activated protein kinase C (PKC)α and PKCδ, and decreased serine phosphorylation of p120-ctn. Further knockdown of PKCα and δ by small interference RNA (siRNA) prevented the pH 6.6-induced downregulation of p120-ctn at AJ and the serine dephosphorylation of p120-ctn. Moreover, PP2 pretreatment and siRNA of c-Src abrogated the pH 6.6-induced PKCδ activation. Together, the c-Src-PKCδ cascade and PKCα regulate the acidic pHe-induced AJ disruption. © 2011 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved. Source


Haga S.B.,Duke University | Kawamoto K.,Duke University | Agans R.,University of North Carolina at Chapel Hill | Ginsburg G.S.,Institute for Genome science and Policy
Genetics in Medicine | Year: 2011

Purpose: Pharmacogenetic testing is one of the primary drivers of personalized medicine. The use of pharmacogenetic testing may provide a lifetime of benefits through tailoring drug dosing and selection of multiple medications to improve therapeutic outcomes and reduce adverse responses. We aimed to assess public interest and concerns regarding sharing and storage of pharmacogenetic test results that would facilitate the reuse of pharmacogenetic data across a lifetime of care. Methods: We conducted a random-digit-dial phone survey of a sample of the US public. Results: We achieved an overall response rate of 42% (n = 1139). Most respondents indicated that they were extremely or somewhat comfortable allowing their pharmacogenetic test results to be shared with other doctors involved in their care management (90% ± 2.18%); significantly fewer respondents (74% ± 3.27%) indicated that they were extremely or somewhat comfortable sharing results with their pharmacist (P < 0.0001). Conclusion: Patients, pharmacists, and physicians will all be critical players in the pharmacotherapy process. Patients are supportive of sharing pharmacogenetic test results with physicians and pharmacists and personally maintaining their test results. However, further study is needed to understand which options are needed for sharing, appropriate storage, and patient education about the relevance of pharmacogenetic test results to promote consideration of this information by other prescribing practitioners. © 2011 Lippincott Williams & Wilkins. Source


Chan D.A.,Stanford University | Chan D.A.,University of California at San Francisco | Sutphin P.D.,Massachusetts General Hospital | Nguyen P.,Stanford University | And 14 more authors.
Science Translational Medicine | Year: 2011

Identifying new targeted therapies that kill tumor cells while sparing normal tissue is a major challenge of cancer research. Using a high-throughput chemical synthetic lethal screen, we sought to identify compounds that exploit the loss of the von Hippel-Lindau (VHL) tumor suppressor gene, which occurs in about 80% of renal cell carcinomas (RCCs). RCCs, like many other cancers, are dependent on aerobic glycolysis for ATP production, a phenomenon known as the Warburg effect. The dependence of RCCs on glycolysis is in part a result of induction of glucose transporter 1 (GLUT1). Here, we report the identification of a class of compounds, the 3-series, exemplified by STF-31, which selectively kills RCCs by specifically targeting glucose uptake through GLUT1 and exploiting the unique dependence of these cells on GLUT1 for survival. Treatment with these agents inhibits the growth of RCCs by binding GLUT1 directly and impeding glucose uptake in vivo without toxicity to normal tissue. Activity of STF-31 in these experimental renal tumors can be monitored by [18F] fluorodeoxyglucose uptake by micro-positron emission tomography imaging, and therefore, these agents may be readily tested clinically in human tumors. Our results show that the Warburg effect confers distinct characteristics on tumor cells that can be selectively targeted for therapy. Source


Tung J.,Duke University | Tung J.,Institute for Genome science and Policy | Tung J.,University of Chicago | Alberts S.C.,Duke University | And 4 more authors.
Trends in Genetics | Year: 2010

Ecological and evolutionary studies of wild primates hold important keys to understanding both the shared characteristics of primate biology and the genetic and phenotypic differences that make specific lineages, including our own, unique. Although complementary genetic research on nonhuman primates has long been of interest, recent technological and methodological advances now enable functional and population genetic studies in an unprecedented manner. In the past several years, novel genetic data sets have revealed new information about the demographic history of primate populations and the genetics of adaptively important traits. In combination with the rich history of behavioral, ecological, and physiological work on natural primate populations, genetic approaches promise to provide a compelling picture of primate evolution in the past and in the present day. © 2010 Elsevier Ltd. Source

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