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Years and Volumes

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Articles from this Volume

Valeria R Mas, Luciana A Mas, Kellie J Archer, Kenneth Yanke, Anne L King, Eric M Gibney, Adrian Cotterell, Robert A Fisher, Marc Posner and Daniel G Maluf

Improvements in immunosuppression have led to the progressive decrease in acute rejection in renal transplant recipients.  Long-term allograft survival is improving; however, late graft loss from chronic allograft nephropathy remains a significant clinical problem.  Non-invasive monitoring after kidney transplantation may represent a useful tool for predicting acute rejection.  Valeria Mas et al. (315-324) evaluated gene expression levels at different post-transplantation times in urine samples from kidney transplant recipients.  Results showed characteristic patterns of mRNA levels in the different kidney transplant patient groups indicating that these levels may reflect allograft function. While prospective studies are needed to confirm these results, the evaluation of molecular markers in urine samples could represent an invaluable resource for monitoring kidney transplant patients and predicting the development of chronic allograft nephropathy.

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Posted by Leah Caracappa on Jun 4, 2007 12:00 AM CDT
Saara Ihalainen, Rabah Soliymani, Erika Iivanainen, Kati Mykkänen, Annele Sainio, Minna Pöyhönen, Klaus Elenius, Hannu Järveläinen, Matti Viitanen, Hannu Kalimo and Marc Baumann

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a vascular dementing disease caused by mutations in the NOTCH3 gene.  The majority of mutations are missense, which lead to an uneven number of cysteine residues in epidermal growth factor-like repeats in the Notch3 receptor extracellular domain (N3ECD).  CADASIL is characterized by degeneration of vascular smooth muscle cells (VSMCs) and the accumulation of N3ECD on VSMCs on small and middle-sized arteries.  In this study, Ihalainen et al. (305-314) characterized the protein expression pattern in cultured human CADASIL VSMCs and identified 11 differentially expressed proteins.  Their results indicate that Notch3 misfolding may lead to endoplasmic reticulum stress resulting in increased reactive oxygen species and cell proliferation inhibition.  Additional data suggests that the angiotension II regulatory feedback loop may become activated thereby enhancing the cells ability to respond to angiotension II stimulation.  An understanding of these interactions enhances current knowledge of this hereditary disease and may lead to improved treatment measures.

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Posted by Leah Caracappa on Jun 3, 2007 12:00 AM CDT
Amanda Chan, Mumtaz Akhtar, Max Brenner, Yi Zheng, Percio Gulko and Marc Symons

Rheumatoid arthritis (RA) is a chronic disorder that causes progressive joint destruction.  Fibroblast-like synoviocytes (FLS) isolated from RA patient joints display proliferative and invasive properties reminiscent of malignant tumor cells.  Rac small GTPases play an important role in tumor cell proliferation and invasion. Here, Chan et al. (297-304) investigated the potential role of Rac proteins in the proliferative and invasive behavior of rheumatoid arthritis fibroblast-like synoviocytes.  Results demonstrate for the first time that Rac proteins play an important role in the aggressive behavior of fibroblast-like synoviocytes isolated from RA patients.  This work also raises the possibility that Rac proteins contribute to synovial hyperplasia, cartilage invasion and destruction, suggesting that signaling elements in Rac-regulated pathways may include novel drug targets for therapeutic intervention in RA.

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Posted by Leah Caracappa on Jun 2, 2007 12:00 AM CDT
Monika Rac, Krzysztof Safranow and Wojciech Poncyljusz

Cell differentiation molecule 36 (CD36) is a transmembrane glycoprotein located on chromosome 7q11.2 encoded by 15 exons.  The defective CD36 gene may be a candidate for several diseases some of which include atherosclerosis, arterial hypertension, diabetes, cardiomyopathy, Alzheimer’s disease, and malaria.  Contradictory data regarding CD36 indicates the necessity for further investigation into its role. In this review, Rac et al. (288-296) summarize the current knowledge regarding CD36 and the consequences of CD36 genetic mutations in various diseases.

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Posted by Leah Caracappa on Jun 1, 2007 12:00 AM CDT
Max Brenner, Teresina Laragione, Nuriza Yarlett and Percio Gulko

Rheumatoid arthritis (RA) is a chronic autoimmune disease for which there is no cure.  RA has a strong genetic component with a heritability of 60%.  The identification of genes contributing to disease susceptibility and severity is expected to generate novel and better therapeutic targets.  T cells play a central role in the pathogenesis of autoimmune arthritis, and several abnormalities in T cell homeostasis have been described in RA.  Brenner et al. (277-287) hypothesized that T cell phenotypes, including frequencies of different subsets of T regulator cells, and their in vitro functional responses could be genetically determined.  Brenner et al. postulated further that the genetic contribution would be accounted for by one of the arthritis regulator quantitative trait loci (QTL) leading to novel clues to gene mode of action in rheumatoid arthritis.  T cells from arthritis susceptible, resistant, and QTL congenic mice were isolated from the thymus, peripheral blood and spleen and analyzed. Their results show for the first time that arthritis quantitative trait loci regulate subsets of T regulatory cells.  Furthermore, major histocompatibility complex (MHC) genes are involved in this process, raising a novel potential explanation for the long-known MHC association with RA and other forms of autoimmune arthritis.

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Posted by Leah Caracappa on May 6, 2007 12:00 AM CDT
Arif Khan, Aijaz Khan, Varun Dwivedi, M Ahmad, S Hakeem and Mohammad Owais

Anticancer drugs are generally plagued by toxic manifestations at doses necessary for control of various forms of cancer.  Incorporating drugs into liposomes not only reduces toxicity but also enhances their therapeutic index. Etoposide (ETP), a derivative of a toxin found in the American Mayapple, has been successfully employed as an antineoplastic agent against various forms of cancer. Earlier attempts have demonstrated usage of liposomised ETP in delaying tumor progression, but such treatments failed to show tumor regression in animal models.  Tuftsin is a tetra peptide reported to have anti-tumor activity in experimental tumor animal models.  Khan et al. (266-276) hypothesized that the combination of tuftsin with a potent antitumor agent could successfully suppress various forms of cancer.  This work evaluated the antitumor potential of liposomal ETP with and without tuftsin against fibrosarcoma in Swiss albino mice.  Tuftsin bearing liposomes significantly reduced tumor volume, delayed tumor growth and increased upregulation of p53wt expression.  The results of the present study suggest that tuftsin incorporation in drug-loaded liposomes may be a promising strategy to treat various forms of cancers including fibrosarcoma.

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Posted by Leah Caracappa on May 5, 2007 12:00 AM CDT
Gloria Calaf and Debasish Roy

Breast cancer is the most common form of malignant disease occurring among women of the western world and environmental substances seem to be involved in this etiology.  Many studies have found an association between human cancer and exposure to agricultural pesticides such as parathion, an organophosphorous pesticide used in agriculture to control mosquito plagues.  An association between breast cancer and prolonged exposure to estrogen suggests this hormone may also play a role in this disease.  However, causative factors for breast carcinogenesis remain an enigma.  Here Calaf and Roy (255-265) determine the effects of 17β estradiol and parathion on human breast epithelial cell transformation.  Results showed that parathion alone and in combination with 17β estradiol induced malignant transformation of an immortalized human breast epithelial cell line.  Additional data suggest that parathion has the potency to cause malignant transformation of breast epithelial cells through modulation of expression of cell cycle regulated genes.  Knowledge of these specific genetic changes is critical for understanding the molecular basis for breast carcinogenesis.

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Posted by Leah Caracappa on May 4, 2007 12:00 AM CDT
Binghua Zhang, Yanqiong Zhang, Jiwei Wang, Yangde Zhang, Jiji Chen, Yifeng Pan, Lifeng Ren, Zhiyuan Hu, Jingfeng Zhao, Mingmei Liao and Shunwei Wang

Hepatocellular carcinoma, a form of cancer originating in liver cells, is a challenging malignancy that results in high patient mortality rates.  While current therapies exist, drawbacks such as cytotoxicity have prompted researchers to seek more effective methods of treatment.  Phage display technology is a powerful tool in this field and may impact clinical issues including functional diagnosis and targeted drug delivery.  Identification of high affinity ligand biomarkers that could specifically discriminate between normal and cancerous cells as well as differentiate between specific types of cancer cells are keys to the development of early detection methods and preoperative treatment strategies.  Panning phage-displayed peptide libraries on intact cells in culture and on the tissues of living animals, often referred to as biopanning, has proven successful for isolating peptides which show high cell-specificity and tissue-specificity.  In this work, Zhang et al. (246-254) used a hepatocellular carcinoma cell line and a normal hepatocyte cell line to carry out subtractive screening with a phage display-7 peptide library.  Their results showed that phage, as well as a synthetic peptide they identified (HCBP1), bound to cell surfaces of hepatoma cell lines and biopsy specimens, but not to normal hepatocytes or non-tumor liver tissues. While further studies are needed to focus on the binding specificity of HCBP1 in human hepatoma tissues and their future applications, these results indicate that the peptide HCBP1 may be a potential candidate for targeted drug delivery in hepatocarcinoma.

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Posted by Leah Caracappa on May 3, 2007 12:00 AM CDT
Hiroyasu Morikawa, Akihiro Tamori, Shuhei Nishiguchi, Masaru Enomoto, Daiki Habu, Norifumi Kawada and Susumu Shiomi

Idiopathic portal hypertension (IPH), or high blood pressure in the portal vein and its branches, is a disorder of unknown origin.  Clinically associated with portal hypertension in the absence of cirrhosis, the pathogenesis of IPH remains poorly understood.  Morikawa et al. (240-245) designed this study to delineate the characteristics of IPH RNA expression in liver specimens from patients with IPH.  Several up-regulated genes were detected, including connective tissue growth factor (CTGF), which showed an intense positive reaction with in situ hybridization studies.  CTGF plays an important role in matricellular regulation related to internal and external cell signaling.  Additionally, analysis of human serum revealed that levels of CTGF in patients with IPH were significantly higher than healthy volunteers.  These results enhance the current knowledge of idiopathic portal hypertension and indicate that overexpression of CTGF may be an important target in this disease.

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Posted by Leah Caracappa on May 2, 2007 12:00 AM CDT
Dong Liang, Zsigmond Benko, Emmanuel Agbottah, Michael Bukrinsky and Richard Zhao

Human immunodeficiency virus type 1 (HIV-1) viral protein R (Vpr) is a virion-associated protein that is highly conserved among HIV, simian immunodeficiency virus and other lentiviruses.  Vpr displays several distinct activities in host cells which include cell cycle arrest and cell killing.  The precise biological role of Vpr-induced apoptosis of target cells is unclear at present, but may represent a host self-destructive mechanism to prevent viral spread.  In this work, Liang et al. (229-239) searched for cellular proteins capable of suppressing Vpr activities.  Using a fission yeast model system, the authors identified a small heat shock protein that was able to specifically inhibit the Vpr activities both in fission yeast and mammalian cells.  The heat shock human paralogue, HSP27, was responsive to HIV infection and responded specifically to vpr gene expression during infection.  These results demonstrate that HSP-targeted strategies may help reduce Vpr-mediated detrimental effects in HIV-infected patients.

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Posted by Leah Caracappa on May 1, 2007 12:00 AM CDT