Flavopiridol increases therapeutic ratio of radiotherapy by preferentially enhancing tumor radioresponse

International Journal of Radiation Oncology, Biology, Physics
Kathy A MasonLuka Milas

Abstract

Recently we reported that inhibition of cyclin-dependent kinases (cdks) by flavopiridol enhanced the radiation response of murine ovarian carcinoma cells in culture. The purpose of this investigation was to extend these studies to in vivo tumor models and test whether flavopiridol increases the therapeutic ratio of radiotherapy. Three transplantable syngeneic mouse tumors were used: mammary carcinoma (MCa-29), ovarian carcinoma (OCa-I), and a lymphoma (Ly-TH). Tumor treatment endpoints included growth delay, cure, and spontaneous lung metastases (OCa-I tumor). The normal tissue endpoint was survival of jejunal crypt cells quantified microscopically. A range of flavopiridol doses from 0.625 to 5.0 mg/kg were given systemically once or twice daily over 5, 10, or 20 days. Combined therapy flavopiridol treatments were initiated either several days before or shortly after the start of single dose or daily fractionated radiotherapy. The major findings of this study are that all three tumors treated with flavopiridol alone responded by tumor growth delay. Two of the tumors (MCa-29 and Ly-TH) responded in a schedule-dependent manner with larger radiation enhancement factors when flavopiridol treatment was started a few hours after irra...Continue Reading

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Citations

Nov 11, 2010·Future Oncology·Walter N HittelmanLuka Milas
Jun 1, 2005·Cancer Research and Treatment : Official Journal of Korean Cancer Association·Suzy KimIl Han Kim
May 9, 2012·FEBS Letters·Steven A Johnsen
Feb 6, 2009·Lung Cancer : Journal of the International Association for the Study of Lung Cancer·Elisabeth KodymDebabrata Saha
Jul 22, 2008·International Journal of Radiation Oncology, Biology, Physics·Takamitsu HaraTomio Inoue
Aug 15, 2006·Radiotherapy and Oncology : Journal of the European Society for Therapeutic Radiology and Oncology·Uma RajuLuka Milas
Aug 15, 2006·International Journal of Radiation Oncology, Biology, Physics·Mary Frances McAleerEric Wickstrom
Jan 10, 2006·Seminars in Oncology·Luka MilasJaffer Ajani
May 6, 2006·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Christopher A BarkerPhilip J Tofilon
Mar 10, 2005·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Saltanat NajmiRobert Wieder

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