May-June 2009 l Vol 15 l No 5-6

Commentary

Research Articles

IGF-1 Expression in Infarcted Myocardium and MGF E Peptide Actions in Rat Cardiomyocytes in Vitro
Anastasia Stavropoulou, Antonios Halapas, Antigone Sourla, Anastassios Phiippou, Efstathia Papageorgiou, Apostolos Papalois, and Michael Koutsilieris
Congestive heart failure (CHF) can be the final result of a series of events including necrosis of the myocardium, coronary artery occlusion, and myocardial infarction (MI). Until recently it was thought that once cells in this tissue were damaged, there was no possibility for regeneration. Stavropoulou et al. examine the role of IGF expression in myocardium repair following MI in Wistar rats. The authors postulate that the IGF-1 isoforms, IGF-1Ea and MGF-E, each have unique roles to play in myocardial repair processes. This work could ultimately impact clinical options in the immediate aftermath of MI.
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Genome-Wide Association Study of Determinants of Anti-Cyclic Citrullinated Peptide Antibody Titer in Adults with Rheumatoid Arthritis
Jing Cui, Kimberly E Taylor, Anita L DeStefano, Lindsey A Criswell, Elena S Izmailova, Alex Parker, Ronenn Roubenoff, Robert M Plenge, Michael E Weinblatt, Nancy A Shadick, and Elizabeth W Karlson
The autoimmune disease rheumatoid arthritis (RA) impacts about one percent of the population and can severely reduce quality of life for those affected. Recent RA studies have zeroed in on genetic variability in an immunity hub, the major histocompatability complex (MHC), as an indicator of susceptibility. Cui et al. push detection of RA indicators a step further by performing a genome–wide association study using anti-cyclic citrullinated peptide (anti-CCP) as a specific and quantitative phenotype of RA. Through an analysis of anti-CCP titer, the authors confirmed that human leukocyte antigen (HLA)  is the most important region for this phenotype. These efforts could have a significant impact on detection of and treatment options for RA.
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A Novel Recombinant Vaccinia Virus Expressing the Human Norepinephrine Transporter Retains Oncolytic Potential and Facilitates Deep-Tissue Imaging
Nanhai Chen, Qian Zhang, Yong A Yu, Jochen Stritzker, Peter Brader, Andreas Schribel, Samuel Samnick, Inna Serganova, Ronald Blasberg, Yuman Fong, and Aladar A Szalay
Virotherapeutics promise to provide tissue-specific treatments for cancer. However, to ensure proper virus targeting, the vector must be closely monitored. To minimize the invasiveness of virus and tumor surveillance, Chen et al. present a novel recombinant form (GLV-1h99) of the vaccinia virus (VACV), an oncolytic virus once used to help eradicate smallpox. After infecting tumor cells, GLV-1h99 promotes cell surface expression of the human norepinephrine transporter (hNET), which facilitates tumor uptake of a radiolabeled tracer that can be visualized non-invasively. These findings present a new way to follow the in vivo progress of virotherapeutics, shedding needed light on treatment efficacy.
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Supplemental Data: PDF (1.1 MB)

Differentiation of Bone Marrow-Derived Endothelial Progenitor Cells Is Shifted into a Proinflammatory Phenotype by Hyperglycemia
Cindy JM Loomans, Rien van Haperen, Jacques M Duijs, Caroline Verseyden, Rini de Crom, Pieter JM Leenen, Hemmo A Drexhage, Hetty C de Boer, Eelco JP de Koning, Ton J Rabelink, Frank JT Staal, and Anton Jan van Zonneveld
Bone marrow–derived endothelial progenitor cells (EPCs) are critical for maintaining the integrity and health of the vasculature. In diabetes, however, the numbers of these cells in the circulation are reduced, which may lead to ischemic vascular disease in these patients. Loomans et al. demonstrate that hyperglycemia drives the fate of EPC away from forming helpful, pro-angiogenic cells capable of remodeling the endothelium to forming proinflammatory cells instead. Their work helps us appreciate the underlying cause of vascular complications in diabetes patients and may serve to outline a specific use of bone marrow cells in neovascularization therapy.
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Analysis Association between Mitochondrial Genome Instability and Xenobiotic Metabolizing Genes in Human Breast Cancer
Walter H Pavicic, Martin Laguens, and Silvina M Richard
Breast cancer is the number one threat to womens’ health worldwide and the race is on to find more successful treatments and strengthen prevention through a greater understanding of its cause. An important measure of a cell’s likelihood to progress to a cancerous state is genomic instability, which can be found wherever DNA is found—including mitochondria. Pavicic et al. explore whether or not mitochondrial genomic instability can be linked with polymorphisms in xenobiotic metabolizing enzymes that could be crucial for protecting breast tissue from carcinogens. By analyzing two markers in the displacement loop (D-loop) of mitochondrial DNA, the authors found that 38 of 94 breast cancer cases (40.42%) showed mitochondrial genomic instability (mtGI), which correlated with alterations in 1 out of 3 xenobiotic metabolizing genes (XMG). This work could further our understanding of the mechanism underlying increased genomic instability and its relation to breast carcinogenesis. 
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Activation of the Cholinergic Antiinflammatory Pathway Reduces Ricin-Induced Mortality and Organ Failure in Mice
Jon G Mabley, Pal Pacher, and Csaba Szabo
Ricin, a compound derived from castor beans, is a potent toxin that causes inflammation, multiple organ failure and death. While the effects of ricin have long been known, there is still no antidote to counteract them. Since nicotine can reduce inflammation in other contexts, Mabley et al. explored the effects of this alkaloid in mice and found it retards the effects of ricin through the cholinergic anti-inflammatory pathway. The authors suggest nicotine administration to ricin exposed patients could provide a greater window of opportunity to apply known, time-sensitive treatments.
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Comparative Mitochondrial Proteomic Analysis of Raji Cells Exposed to Adriamycin
Yu-Jie Jiang, Qing Sun, Xiao-Sheng Fang, and Xin Wang
Chemoresistance and chemotoxicity are persistent problems in the treatment of cancers such as non-Hodgkin lymphoma (NHL). One consequence of these issues is a failure to increase long-term disease free rates in the majority of patients treated for intermediate and high grade NHL. To dissect the mechanism of resistance and toxicity to a commonly used treatment for NHL, Jiang et al. mined the mitochondrial proteome to discern the effects of adriamycin (ADR) on global protein expression. Their work could ultimately help predict patient response to therapy and lead to new strategies for the treatment of NHL.
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Review Articles

Recent Advances Relating to the Clinical Application of Naked Monoclonal Antibodies in Solid Tumors
Andreas Argyriou and Haralabos P Kalofonos
Molecular biology has played a major role in the development of treatments for solid tumors over the last few years.  Several humanized and chimeric monoclonal antibodies (MAbs) targeting HER2, EGFR, and VEGF have been employed in treating solid tumors – including breast, colorectal, lung, head and neck, and gynecologic cancers.  Argyriou and Kalofonos review the recent advances in clinical data regarding antibody-based therapies in the management of solid tumors, and discuss perspectives on the future of antibody-based therapeutics.
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