Selective kinase inhibitors have had a substantial impact on the field of medical oncology. Whereas these agents can elicit dramatic clinical responses in some settings, their activity is generally limited to a subset of treated patients whose tumor cells harbor a specific genetic lesion. We have established an automated platform for examining the sensitivity to various molecularly targeted inhibitors across a large panel of human tumor-derived cell lines to identify additional genotypecorrelated responses that may be clinically relevant. Among the inhibitors tested in a panel of 602 cell lines derived from a variety of human cancers, we found that a selective inhibitor of the anaplastic lymphoma kinase (ALK) potently suppressed growth of a small subset of tumor cells. This subset included lines derived from anaplastic large cell lymphomas, nonsmall-cell lung cancers, and neuroblastomas. ALK is a receptor tyrosine kinase that was first identified as part of a protein fusion derived from a chromosomal translocation detected in the majority of anaplastic large cell lymphoma patients, and has recently been implicated as an oncogene in a small fraction of non-small-cell lung cancers and neuroblastomas. Significantly, sensitivity in these cell lines was well correlated with specific ALK genomic rearrangements, including chromosomal translocations and gene amplification. Moreover, in such cell lines, ALK kinase inhibition can lead to potent suppression of downstream survival signaling and an apoptotic response. These findings suggest that a subset of lung cancers, lymphomas, and neuroblastomas that harbor genomic ALK alterations may be clinically responsive to pharmacologic ALK inhibition. [Cancer Res 2008;68(9):3389-95]

. The majority of respondents used some form of CAM for general purpose, whereas far fewer used CAM for diabetes care. The most widely used CAM categories were food home remedies, other home remedies, and vitamins. The following health self-management predictors were related to the use of different categories of CAM therapies: personal characteristics (ethnicity), health status (number of health conditions), personal resources (education), and financial resources (economic status). Discussion. CAM is a widely used component of health self-management among rural among older adults with diabetes. Research on CAM use will benefit from theory that considers the specific behavior and cognitive characteristics of CAM therapies.

Purpose-The purposes of this study were to assess the level of foot self-care performed in a rural, multiethnic population of older adults and to identify factors associated with foot self-care. Methods-TheEvaluating Long-term Diabetes Self-management Among Elder Rural Adults study included a random sample of 701 African American, Native American, and white adults from 2 rural North Carolina counties. Participants completed in-home interviews, 5 foot self-care practices from the Summary of Diabetes Self-Care Activities (SDSCA), functional status measures, and measures of education and support for foot care.Results-Foot care practices/behaviors reported at least 6 days/week ranged from 35.6% for inspecting shoes to 79.2% for not soaking feet. Four independent predictors of the SDSCA summary foot care index score were observed: having been shown how to care for feet (P < .0001), female gender (P = .03), having had a doctor check nerves in feet in past year (P = .02), and not receiving support caring for feet (P = .0425).Conclusions-These findings indicate that educating patients about foot self-care may encourage routine foot care but that those dependent on either formal or informal support to perform foot care do so less frequently than those who perform it independently.Diabetes mellitus and chronic diabetes complications place an enormous burden on the health care system and health care resources. More than 18 million Americans, or 6.3% of the population, have diabetes. 1 Diabetes contributes substantially to morbidity and mortality, with foot complications being among the most serious and costly complications of diabetes. Foot ulcerations often lead to amputation if not detected early and managed properly among persons Correspondence to: Sara A. Quandt.Correspondence to Ronny A. Bell, PhD, MS, Department of Public Health Sciences, Wake Forest University School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157-1063 (rbell@wfubmc.edu This study will examine the foot self-care behaviors of older adults in a rural triethnic community. Specifically, the following questions will be addressed: (1) What is the level of foot self-care being performed in this population? and (2) What demographic, health, medical care, and support characteristics are associated with foot self-care behaviors? Methods Study DescriptionThe Evaluating Long-term Diabetes Self-management Among Elder Rural Adults (ELDER) study, a 4-year study funded by the National Institute on Aging and the National Center for Minority Health and Health Disparities, is a population-based, cross-sectional survey designed to comprehensively assess the self-care strategies of older rural adults (age ≥65 years) with diagnosed diabetes and the impact of these strategies on diabetes control. Participants for the study were selected from two counties in central North Carolina. The counties were selected because they are largely rural, have large numbers of ethnic minorities and persons living below the poverty level, and the investigative team h...

HSV-1 inhibits apoptosis of infected cells, presumably to ensure that the infected cell survives long enough to allow completion of viral replication. Because cytotoxic lymphocytes kill their targets via the induction of apoptosis, protection from apoptosis could constitute a mechanism of immune evasion for HSV. Several HSV genes are involved in the inhibition of apoptosis, including Us5, which encodes glycoprotein J (gJ). Viruses deleted for Us5 showed defects in inhibition of caspase activation after Fas ligation or UV irradiation. Transfected cells expressing the Us5 gene product gJ were protected from Fas- or UV-induced apoptosis, as measured by morphology, caspase activation, membrane permeability changes, or mitochondrial transmembrane potential. In contrast, caspase 3 activation in mitochondria-free cell lysates by granzyme (gr)B was inhibited equivalently by Us5 deletion and rescue viruses, suggesting that gJ is not required for HSV to inhibition this process. However, mitochondria-free lysates from transfected cells expressing Us5/gJ were protected from grB-induced caspase activation, suggesting that Us5/gJ is sufficient to inhibit this process. Transfected cells expressing Us5/gJ were also protected from death induced by incubation with purified grB and perforin. These findings suggest that HSV has a comprehensive set of immune evasion functions that antagonize both Fas ligand- and grB-mediated pathways of CTL-induced apoptosis. The understanding of HSV effects on killing by CTL effector mechanisms may shed light on the incomplete control of HSV infections by the immune system and may allow more rational approaches to the development of immune modulatory treatments for HSV infection.