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Pneumococcal Vaccine Reduces Child Deaths In Developing Countries
A new trial has found that pneumococcal vaccine is effective in preventing severe pneumonia, the leading cause of death among children in developing countries. Co-ordinated by the National Institute for Health and Welfare (THL) between 2000 and 2004, a large scale efficacy trial first of its kind in Asia - was carried out in the Philippines to investigate the effect of an investigational pneumococcal vaccine.
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MiR-196a Promotes The Metastases Of Tumors
MicroRNAs are small RNA molecules of 20-25 nucleotides length, regulating gene expression by inhibition of transcription or translation of proteins. High levels of miR-196a, a microRNA suppressing the expression of specific homebox genes that are of high relevance for the development of the human embryo, activated oncogenic pathways inside human tumor cells and induced tumor cell dissemination. miR-196a increased the chemosensitivity towards platin derivatives such as cisplatin and oxaliplatin and might be a useful biomarker.
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The Melanoma Research Alliance Awards Nearly Two Million Dollars In Research Grants That Address The Gap In Translational Science
The Melanoma Research Alliance (MRA) announced the recipients of nearly two million dollars in grants to fund 13 individual scientists pursuing innovative melanoma research proposals. This second round of MRA grants is focused on research that addresses the gap in translational science.
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Adenoviral Vector Specifically Targeted To EphA2 Receptor In Pancreatic Cancer Cells

Pancreatic cancer is a devastating disease with poor prognosis. This warrants the development of novel therapies including gene therapy. However, clinical studies have demonstrated poor efficacy of adenoviral gene therapy because of the absence of adenoviral binding sites on pancreatic cancer cells such as the coxsackie and adenovirus receptor (CAR). Circumventing CAR-mediated entry therefore seems a promising option to improve adenoviral entry into pancreatic cancer cells and to enhance the efficacy of adenoviral vectors. A research team led by Dr. Piter J Bosma from University of Amsterdam addressed this question. Their study was published on June 14, 2009 in the World Journal of Gastroenterology. They present a novel adenoviral vector that binds to the EphA2 receptor (EphA2R). This receptor is highly expressed in several solid tumors including pancreatic cancer. YSA, a small peptide ligand that binds the EphA2R with high affinity, was inserted into the HI loop of the adenovirus serotype 5 fiber knob. To further increase the specificity of this vector, binding sites for native adenoviral receptors, the coxsackie and adenovirus receptor (CAR) and integrin, were ablated from the viral capsid. The ablated retargeted adenoviral vector was produced on 293T cells. Specific targeting of this novel adenoviral vector to pancreatic cancer was investigated on established human pancreatic cancer cell lines. Upon demonstrating specific in vitro targeting, in vivo targeting to subcutaneous growing human pancreatic cancer was tested by intravenous and intraperitoneal administration of the ablated adenoviral vector. They found that ablation of native cellular binding sites reduced adenoviral transduction at least 100-fold. Insertion of the YSA peptide in the HI loop restored adenoviral transduction of EphA2R-expressing cells but not of cells lacking this receptor. YSA-mediated transduction was inhibited by addition of synthetic YSA peptide. The transduction specificity of the ablated retargeted vector towards human pancreatic cancer cells was enhanced almost 10-fold in vitro. In a subsequent in vivo study of a nude (nu/nu ) mouse model however, no increased adenoviral targeting to subcutaneously growing human pancreas cancer nodules was seen upon injection into the tail vein, nor upon injection into the peritoneum. Although re-directing of the adenoviral vector has been reported, this is the first paper showing effective uptake of adenoviral vector by the EphA2R that is present on solid tumors. Notes: Reference: van Geer MA, Bakker CT, Koizumi N, Mizuguchi H, Wesseling, JG, Oude Elferink RPJ, Bosma PJ. Ephrin A2 receptor targeting does not increase adenoviral pancreatic cancer transduction in vivo. World J Gastroenterol 2009; 15(22): 2754-2762 Available, from: URL: http://www.wjgnet.com/1007-9327/15/2754.asp Correspondence to: Dr. Piter J Bosma, Liver Center AMC, University of Amsterdam, Meibergdreeg 69/71, 1105BK Amsterdam, The Netherlands. Lai-Fu Li World Journal of Gastroenterology


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