Die Erforschung der Mechanismen und Interaktionen zwischen Bioaktivation von 5-FU und HSV-1 Onkolyse und die Entwicklung einer quantitativen Erfassung der Virus Replikation mittels PET bei der Behandlung diffuser kolorektaler Metastasen der Leber mit gentechnisch veränderten Herpes Simplex Viren

• Applicant: Dr. Yakup Kulu
• Subject Area: General and Visceral Surgery
• Term: from 2005 to 2007
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 5455348

Unlike patients with other solid tumors, patients with colon and rectal carcinoma commonly develop liver metastases without concomitant spread to other organs. Nonetheless, for patients with unresectable liver metastases from colon carcinoma, current therapies only prolong survival on average by several months. Thus, investigation into new therapeutic approaches is clearly warranted. Viral replication in tumor cells leads to their destruction, with release of progeny virion that can infect adjacent cancer cells in a process referred to as viral oncolysis. Intratumoral conversion of 5-FC to 5-FU by the yeast cytosine deaminase transgene when added to HSV-1 oncolysis enhances efficacy. We propose experiments to elucidate mechanisms of interaction between prodrug bioactivation and HSV-1 oncolysis. We also propose to develop positron emission tomographic (PET) imaging to quantitatively assess viral replication. While PET has been used to examine gene expression, we propose to develop PET to quantitatively image viral replication. Presently, detection of viral replication requires biopsy (or removal) of tissue followed by analysis using molecular techniques such as immunohistochemical staining, or PCR amplification of viral DNA or RT-PCR of viral mRNA. Because these techniques are invasive, cumbersome, and non-quantitative, they are not useful in human clinical trials of HSV-1 oncolysis. Accordingly a strong rationale exists for development of minimally invasive imaging methods to quantitatively assess sites of HSV-1 replication.

• DFG Programme: Research Fellowships
• International Connection: Switzerland, USA
• Host: Professor Dr. Kenneth K. Tanabe