PMID: 11899199Mar 20, 2002Paper

Ganciclovir prodrug therapy is effective in a murine xenotransplant model of human lung cancer

The Annals of Thoracic Surgery
Roland KurdowHolger Kalthoff

Abstract

Therapy failures have been reported for retroviral gene transfer of herpes simplex virus thymidine kinase (HSV-TK) gene followed by systemic ganciclovir application in human lung cancer. Use of the HSV-TK mutant TK30 in combination with a VSV-G pseudotyped retroviral vector was found to enhance the efficacy of prodrug therapy. The present study evaluated this therapeutic strategy in human non-small cell lung cancer cell lines in a preclinical murine xenotransplant model. Intrathoracally induced by HSV-TK30 transduced non-small cell lung cancer cell lines Colo 699 (adenocarcinoma) and KNS 62 (squamous cell carcinoma) were monitored for local tumor growth, survival, and metastases. So-called bystander effects were investigated in tumors consisting of as little as 25% TK30 transfected cells and by analysis of gap junctional protein connexin-43 expression. Survival was significantly prolonged, and tumor growth and pleural metastases were reduced in HSV-TK30-positive tumors of both cell lines. A significant therapeutic effect in bystander experiments was observed in squamous cell carcinoma. This was correlated with higher expression of connexin-43. Delivery of HSV-TK30 in a VSV-G pseudotyped retroviral vector and subsequent ganciclo...Continue Reading

References

Sep 15, 1993·Proceedings of the National Academy of Sciences of the United States of America·W S PearD Baltimore
May 9, 2000·The Annals of Thoracic Surgery·A S BoehleD Henne-Bruns
Jan 13, 2001·The Annals of Thoracic Surgery·E S LambrightL R Kaiser

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Citations

Feb 8, 2005·Clinical Lung Cancer·Thomas T PoulsenHans S Poulsen
Mar 20, 2002·The Annals of Thoracic Surgery·W Roy Smythe
May 19, 2011·Expert Opinion on Therapeutic Targets·Davide LosaSophie Crespin
Sep 26, 2003·Seminars in Surgical Oncology·Jonathan C Daniel, W Roy Smythe

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