Myeloma Xenograft Destruction by a Nonviral Vector Delivering Oncolytic Infectious Nucleic Acid

The feasibility of using a nonviral vector formulation to initiate an oncolytic viral infection has not been previously demonstrated. We therefore sought to determine whether infectious nucleic acid (INA) could be used in place of virus particles to initiate an oncolytic picornavirus infection in vivo. Infectious RNA encoding coxsackievirus A21 (CVA21) was transcribed from plasmid DNA using T7 polymerase. Within 48 hours of injecting this RNA into KAS6/1 myeloma xenografts, high titers of infectious CVA21 virions were detected in the bloodstream. Tumors regressed rapidly thereafter and mice developed signs of myositis. At euthanasia, CVA21 was recovered from regressing tumors and from skeletal muscles. Treatment outcomes were comparable following intratumoral injection of naked RNA or fully infectious CVA21 virus. Dose–response studies showed that an effective oncolytic infection could be established by intratumoral injection of 1 µg of infectious RNA. The oncolytic infection could also be initiated by intravenous injection of infectious RNA. Our study demonstrates that INA is a highly promising alternative drug formulation for oncolytic virotherapy.     

New and emerging technologies for genetic toxicity testing

The International Life Sciences Institute (ILSI) Health and Environmental Sciences Institute (HESI) Project Committee on the Relevance and Follow‐up of Positive Results in In Vitro Genetic Toxicity (IVGT) Testing established an Emerging Technologies and New Strategies Workgroup to review the current State of the Art in genetic toxicology testing. The aim of the workgroup was to identify promising technologies that will improve genotoxicity testing and assessment of in vivo hazard and risk, and that have the potential to help meet the objectives of the IVGT. As part of this initiative, HESI convened a workshop in Washington, DC in May 2008 to discuss mature, maturing, and emerging technologies in genetic toxicology. This article collates the abstracts of the New and Emerging Technologies Workshop together with some additional technologies subsequently considered by the workgroup. Each abstract (available in the online version of the article) includes a section addressed specifically to the strengths, weaknesses, opportunities, and threats associated with the respective technology. Importantly, an overview of the technologies and an indication of how their use might be aligned with the objectives of IVGT are presented. In particular, consideration was given with regard to follow‐up testing of positive results in the standard IVGT tests (i.e., Salmonella Ames test, chromosome aberration assay, and mouse lymphoma assay) to add weight of evidence and/or provide mechanism of action for improved genetic toxicity risk assessments in humans. Environ. Mol. Mutagen., 2011. © 2010 Wiley‐Liss, Inc.     

Ultraviolet Spectroscopy as a Tool in Therapeutic Protein Development

Ubiquitous ultraviolet absorption spectroscopy, despite the availability of more sophisticated techniques, remains an indispensable tool that can give an initial insight into the concentration and aggregation state of protein samples. The high degree of reproducibility afforded by diode-array spectrophotometers, combined with their powerful vendor-supplied algorithms, presents an opportunity for improving the accuracy and throughput for their use in pharmaceutical development. In this review, factors important to optimal utilization of the technique, as applied to the development of monoclonal antibodies, are discussed, and specific methodologies are described. In particular, techniques to probe the intrinsic structural properties of proteins, and their behavior under a wide variety of conditions, through the application of second-derivative spectroscopy combined with advanced computational treatments are presented. The information contained in this review is specifically directed to practitioners of the technique in contemporary research and development settings.     

Health Care Satisfaction: Effects of Immigration,Acculturation, Language

Differences in health care satisfaction can alter patterns of health care utilization and so affect health outcomes, but little is known about variation in satisfaction in relation to immigration status. Health care satisfaction is analyzed with survey data from state public health program patients. Overall health care satisfaction is higher for first generation Hispanic immigrants and lower among those in the second generation compared to white Americans—consistent with the pattern termed the “healthy migrant effect.” This pattern is more pronounced for Portuguese-speaking immigrants and is not explained by self-reported health, communication ability or acculturation. Satisfaction with specific aspects of health care follows different patterns that may be explained by differences in experiences and culture. As anticipated by segmented assimilation theory, we find variation in cross-generational patterns of health care satisfaction both within and between ethnic groups. This variation indicates the importance of distinguishing Portuguese-speakers from Spanish-speakers and of taking into account differences in the ways they are able to communicate with health care providers as well as differences in their orientations toward health care. Our disparate findings with other immigrant groups also reinforce limiting expectations of a “healthy migrant effect” to Latinos. Finally, the variable influences on different satisfaction measures indicate the importance of considering the relative influence of culturally-based orientations and health care experiences on the specific outcomes measured, with particular sensitivity to acceptance of individualized standards of care.