There are two main areas of basic research occurring in the laboratory of Dr. Douglas Fraker. Both areas relate to his interest in regional treatment of advanced cancers.
- The first area of research involves the use of melphalan with acidic perfusate. We have developed an animal model in which isolated limb perfusion (ILP) is performed on nude rats that have been xenografted with human melanoma, sarcoma, and colon carcinoma. In each of these tumors, a change in the pH of the perfusate from 7.4 to between 6.8 and 6.9 markedly enhances the tumor response to melphalan, and in fact, the majority of tumors undergo a complete regression. In addition, in limbs with xenografted melanoma, levels of nitric oxide have been found to be increased after perfusion with acidic media, and this effect is seen only in limbs that have xenografted tumor (tumor specific). It is believed that this burst of nitric oxide may play an important role in the enhanced tumor response that is seen. Specifically, since nitric oxide is a powerful modulator of vessels, it is believed that the tumor vasculature may be negatively affected by the acute increase in nitric oxide levels. Another mechanism that has been postulated to explain the effect of acidic perfusate includes the induction of apoptosis of tumor cells by the higher levels of nitric oxide. These potential mechanisms are currently being investigated both in vitro and in vivo in our animal model. Ultimately, it is hoped that the mechanisms for the enhanced tumor response with acidic perfusate may be delineated and eventually used in clinical trials and treatment.
- The second area of study is related to our ongoing clinical project of intraperitoneal photodynamic therapy for carcinomatosis and sarcomatosis of the abdomen. We currently have studies that involve the analysis of tissue specimens taken during clinical surgery and the development of an animal model to investigate the use of new photosensitizers.