Henry Simpkins, MD, PhD hsimpkins@nshs.edu

In order to create stronger and safer chemotherapies, scientists are studying the molecular mechanisms of cisplatin resistance that develops in tumor cells. Henry Simpkins, MD, and his colleagues utilized the cDNA microarray technique to compare the genes altered in a cisplatin-resistant human ovarian carcinoma cell line when compared to the parental sensitive cell line. The subsequent transfection into cisplatin-sensitive cells of full-length candidate genes show that upregulation of Dihydrodiol dehydrogenase (DDH - an enzyme in a family of aldo-keto reductases known to be involved in the de novo detoxification processes) is intimately involved in the development of the cisplatin resistance phenotype. In addition, they have demonstrated that cells with intrinsically high levels of DDH (i.e. A549, a human lung cancer cell line) possess resistance to platinum-based chemotherapy, as does transfection of DDH into a wide variety of different cancer cell types, including cells derived from human cervical, lung, germ cell and other ovarian cancers. Recently, it has been shown that the glucose analogue 2 deoxyglucose (2 DG), a clinically relevant inhibitor of glucose metabolism, enhances cisplatin cytotoxity in head and neck carcinomas. They are now studying whether this glucose inhibitor sensitizes ovarian carcinoma cells to cisplatin and if this is accompanied by changes in DDH and ROS levels.
 

		Name:   Jianli Chen Position:   Research Associate Research:   Studies the effects of cancer drugs on tumor cells. Email:   jchen3@nshs.edu
		Name: Nancy Tricorico Position: Executive Secretary Staten Island University Hospital Pathology & Laboratory Medicine Email: ntricorico@siuh.edu Phone: 718-226-4130 Fax: 718-226-4185

Select Publications:

Jianli Chen, Mahesha Adikari, Rajash Pallai, Hemant K. Parekh, Henry Simpkins: Dihydrodiol dehydrogenases regulate the generation of reactive oxygen species and the development of cisplatin resistance in human ovarian carcinoma cells.  Cancer Chemotherapy Phamarcology, 61: 979-987, 2008.

H.B. Deng, M. Adikari, H. Parekh and *H. Simpkins: Ubiquitous induction of resistance to platinum drugs in human ovarian, cervical, germ cell and lung carcinoma tumor cells overexpressing isoforms 1 and 2 of dihydrodiol dehydrogenase.  Cancer Chemotherapy Pharmacology, 54: 301-307, 2004. 

H.B. Deng, H.K. Parekh, K.-C. Chow and *H. Simpkins: Increased expression of dihydrodiol dehydrogenase induces resistance to cisplatin in human ovarian carcinoma cells.  Journal of Biological Chemistry, 277: 15035-15043, 2002.