Detailed Biography:

Research Description: Investigations on the mechanisms involved in the death of tumor cells may provide important insights into potential novel treatment strategies for patients with cancer. Recent information indicates that the death process is finely regulated by the tumor target's own genetic program. It has also become apparent that chemotherapy works by inducing a tumor cell to kill itself in a process called apoptosis. Dr. Lichtenstein has been studying the process by which tumor cells die for many years. Initially, he worked in the area of tumor immunology and investigated how lymphocyte cells of the immune system killed tumor cells. This was followed by studies on tumor cell death induced by neutrophilsand neutrophil products, namely reactive oxygen intermediates and proteins secreted from neutrophil granules. Most recently, he has extended his work to investigate apoptotic death mediated by chemotherapeutic agents. Much of the work has been performed in the human tumor model multiple myeloma, involving dissection of how interleukin-6 protects myeloma tumor cells from apoptotic death due to dexamethasone and other agents used to treat this disease. In addition, studies on expression of the BCL-2 gene in myeloma plasma cells have shown it to protect the tumor cells from death and to be an agent of induced resistance as the expression of BCL-2 increases in tumor cells that survive an initial exposure to chemotherapy. Dr. Lichtenstein's work on tumor cell apoptosis is currently being extended to two other human tumors, chronic lymphocytic leukemia (CLL) and squamous cell carcinoma of the head and neck (SCCH&N). He has identified BCL-2 as an important mediator of tumor cell protection in these malignant cells and has shown, during in vitro experiments, that use of the drug taxol can phosphorylate BCL-2, inactivate it and, thus, sensitize these cells for heightened apoptotic death. Phase I studies of taxol in CLL and SCCH& Nare planned to start in the Fall of 1996. In these studies, taxol will be dose escalated gradually and phosphorylation and inactivation of BCL-2 in tumor cells as well as tumor response will be assayed.