tailieunhanh - Báo cáo hóa học: " Adenoviruses with an avb integrin targeting moiety in the fiber shaft or the HI-loop increase tumor specificity without compromising antitumor efficacy in magnetic resonance imaging of colorectal cancer metastases"

Adenoviruses with an avb integrin targeting moiety in the fiber shaft or the HI-loop increase tumor specificity without compromising antitumor efficacy in magnetic resonance imaging of colorectal cancer metastases | Lavilla-Alonso et al. Journal of Translational Medicine 2010 8 80 http content 8 1 80 RESEARCH JOURNAL OF TRANSLATIONAL MEDICINE Open Access Adenoviruses with an avp integrin targeting moiety in the fiber shaft or the HI-loop increase tumor specificity without compromising antitumor efficacy in magnetic resonance imaging of colorectal cancer metastases 3 4 5 Sergio Lavilla-Alonso 1 Gerd Bauerschmitz Usama Abo-Ramadan Juha Halavaara Sophie Escutenaire 1 4 16 t t lulia Diaconu Turgut Tatlisumak Anna Kanerva Akseli Hemminki T Sari Pesonen T Abstract Background Colorectal cancer is often a deadly disease and cannot be cured at metastatic stage. Oncolytic adenoviruses have been considered as a new therapeutic option for treatment of refractory disseminated cancers including colorectal cancer. The safety data has been excellent but tumor transduction and antitumor efficacy especially in systemic administration needs to be improved. Methods Here the utility of avb integrin targeting moiety Arg-Gly-Asp RGD in the Lys-Lys-Thr-Lys KKTK domain of the fiber shaft or in the Hl-loop of adenovirus serotype 5 for increased tumor targeting and antitumor efficacy was evaluated. To this end novel spleen-to-liver metastatic colorectal cancer mouse model was used and the antitumor efficacy was evaluated with magnetic resonance imaging MRI . Results Both modifications RGD in the Hl-loop or in the fiber shaft increased gene transfer efficacy in colorectal cancer cell lines and improved tumor-to-normal ratio in systemic administration of the vector. Conclusions Antitumor potency was not compromised with RGD modified viruses suggesting increased safety profile and tumor specificity. Background Colorectal cancer is the fourth most common type of cancer in men and the third most common in women worldwide and more than one million people are diagnosed with colorectal cancer every year. Incidence rates have increased during past decades while