Xiaoying Yin, MD

Xiaoying Yin, MD, is working on several research projects.

1. Evaluate the anti-tumor effect of enzastaurin, a PKC-β inhibitors on HNSCC. Protein kinase C (PKC) is a family of serine/threonine kinases known to play critical roles in the signal transduction pathways involved in growth factor response, cell proliferation, differentiation, and apoptosis. Therefore, the PKCs are potential targets for cancer therapies. Enzastaurin is a specific protein kinase C beta (PKC-β) inhibitor that has been reported effective for inhibiting tumor growth in many other tumor types. In addition to specifically inhibiting tumor-derived VEGF-induced angiogenesis, it has been reported that enzastaurin can directly inhibit proliferation, and induce apoptosis which will inhibit tumor growth in vitro and in vivo. Our research project are aimed to (1) evaluate the effect of enzastaurin on HNSCC as an antitumor agent alone and as a radiosensitizer with radiation both in vitro with HNSCC cell lines and in vivo using a novel mice model that mimics the delivery of concurrent chemoradiation in HNSCC patients, (2) help unravel the mechanism of the effect of enzastaurin and cisplatin by analyzing enzastaurin/cisplatin- induced protein level changes in signal transduction pathways and gene expression changes that are due to enzastaurin/cisplatin and radiation treatment, and (3) refine this murine model of chemoradiation responsiveness for use with other novel agents.

2. Microarray study of head and neck squamous cell carcinoma (HNSCC). Microarray technology has been widely used for comprehensive gene expression analysis. Large scale microarray analysis enabled us to analyze simultaneous changes of the expression of thousands of genes in a single experiment and identify significant patterns. In HNSCC, gene expression signatures have been reported to associate with carcinogenesis, metastasis potential and recurrent disease. However, none of these are large scale studies.

Working with Carol G. Shores, MD, PhD, and Neil Hayes, MD (Division of Medical Oncology), we have collected hundreds of HNSCCA tumors from patients at UNC. Using this tissue bank, we are generating micoarray expression data of these tumors. Our goal is using gene expression profile to help us to find genes that are important to response to radiation/chemotherapy, tumor progress and metastasis, and tumor subtypes. In addition, we will use this tissue bank to perform single-nucleotide polymorphism array analysis of HNSCCA.

3. Evaluate the anti-tumor effect of Hsp90 inhibitors on HNSCC. Collaborating with Biogen Idec Corporation, we have studied a novel class of chemotherapy agents, Hsp90 inhibitors, EC78. Hsp90 stabilizes cellular proteins, and inhibition can lead to the degradation of several tumor related proteins, thereby interrupting several pathways simultaneously. The Hsp90 inhibitor EC78 has been shown to radiosensitize HNSCC in a xenograft model, with minimal side effects and disruption of the expected proteins.

4. Investigate the mechanism of cancer cachexia. With Marion E. Couch, MD, PhD, several residents and medical students, we are working on the mechanism of cancer cachexia syndrome, a wasting syndrome which afflicts so many cancer patients. The contribution of both the host and the tumor to cancer cachexia is being actively investigated. The laboratory has published work describing a head and neck animal model for cancer cachexia and work implicating the innate immune system (Toll-like receptors) in the severity of the wasting syndrome.