Radiotherapy preclinical studies

Studies of liver effects from external beam radiotherapy date back to the 1920s [13-16]. Brachy-therapy in the lung and liver also has a significant history of investigation [17]. Preclinical studies utilized a variety of animal models, and various infusion methods (vein, heart, aorta, hepatic artery, and portal vein) with and without liver tumors to study microsphere deposition in normal and tumors tissues. Common observations in animals and humans confirmed arterial delivery of microspheres causes them to embed in the periphery of the tumor in highly nonuniform (but not random) patterns with nearly all located within a few millimeters of tumor... 

Hydroxyurea is an oral agent that inhibits ribonucleotide diphosphate reductase and interferes with the synthesis of DNA, specifically the S phase of the cell cycle. Sinclair et al. have demonstrated in preclinical animal models that hydroxyurea may inhibit cells from leaving the Gj radiosensitive phase and entering the radioresistant S phase (9). Early studies have demonstrated little or no efficacy associated with the use of single-agent hydroxyurea (10). It has received FDA approval in the use of head and neck cancer when administered concomitantly with radiotherapy based upon promising results from earlier studies (11). 

Others studies have combined radiation therapy with IL-3 immunotherapy in preclinical models (Chiang et al. 2000 Tsai et ah 2006). However, these studies and similar involving other immunotherapy-based approaches in combination with radiotherapy have not moved forward to clinical trials. 

Marion Cottier and collaborators summarized in their chapter a set of observations that lead to the definition of NO as radiosensitizer molecule in bacteria and mammalian tumor cells. The effect of NO in the sensitization of tumor cell to radiotherapy has been demonstrated in preclinical and clinical studies. These effects can be either direct, by the cellular induction or generation of NO by the target tissue (NOS-mediated induction or activation) as revealed by Peter Siesjo in his chapter, or indirect by the use of NO-releasing compounds such as NO donors extensively discussed in these chapters. 

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