University of Louisville
Cisplatin Uptake Analysis in a Murine Xenograft of Ovarian Carcinoma Cells with Arsenic Trioxide
Institution
University of Louisville
Faculty Advisor/ Mentor
Cyril Helm; Christopher States
Abstract
Ovarian cancer affects over 200,000 women worldwide yearly and leads to the death of 125,000 of them, making it the 4th leading cause of cancer death in women in the United States. Due to the fact that there are no early warning signs, the disease has often spread within the peritoneal cavity by the time it is detected. Currently, standard treatment for the disease is combined cytoreductive surgery and intraperitoneal chemotherapy with a platinum-based drug (cisplatin) and a taxane. Frontline treatment will produce a complete response in 67% of patients but, of these, the disease will return in 65% of patients. Therefore, there is need for improved treatment. Cisplatin (CDDP) is the most administered chemotherapy drug for humans. Arsenic trioxide has been shown in vitro to augment the efficacy of the CDDP in combination with hyperthermia. We have developed a mouse xenograft model for metastatic, platinum resistant human ovarian cancer to test the efficacy of combined treatment modalities. Preliminary data suggest that platinum is readily accumulated and retained in the tumors exposed to cisplatin either alone or in combination with arsenic and/or hyperthermia. The results suggest that the model will be useful for evaluating intraperitoneal delivery of new combination chemotherapies and for determining modulation of tumor responses related to cisplatin resistance.
Cisplatin Uptake Analysis in a Murine Xenograft of Ovarian Carcinoma Cells with Arsenic Trioxide
Ovarian cancer affects over 200,000 women worldwide yearly and leads to the death of 125,000 of them, making it the 4th leading cause of cancer death in women in the United States. Due to the fact that there are no early warning signs, the disease has often spread within the peritoneal cavity by the time it is detected. Currently, standard treatment for the disease is combined cytoreductive surgery and intraperitoneal chemotherapy with a platinum-based drug (cisplatin) and a taxane. Frontline treatment will produce a complete response in 67% of patients but, of these, the disease will return in 65% of patients. Therefore, there is need for improved treatment. Cisplatin (CDDP) is the most administered chemotherapy drug for humans. Arsenic trioxide has been shown in vitro to augment the efficacy of the CDDP in combination with hyperthermia. We have developed a mouse xenograft model for metastatic, platinum resistant human ovarian cancer to test the efficacy of combined treatment modalities. Preliminary data suggest that platinum is readily accumulated and retained in the tumors exposed to cisplatin either alone or in combination with arsenic and/or hyperthermia. The results suggest that the model will be useful for evaluating intraperitoneal delivery of new combination chemotherapies and for determining modulation of tumor responses related to cisplatin resistance.