Head and Neck Cancer Research Laboratory - UCLA
The focus of this laboratory is to explore the molecular basis for the development and progression of head and neck squamous cell carcinoma (HNSCC). Advanced head and neck cancer carries a poor prognosis, and a goal of this lab is to search for more effective and less toxic treatments for this devastating disease.
Current Research Projects
- Curcumin suppression of head and neck cancer. Curcumin is a naturally occurring plant phenol that is a commonly used spice, also known as turmeric. We have found that curcumin treatment of HNSCC both in vitro and in vivo results in significant suppression of tumor growth. In addition, a liposomal curcumin formulation can be given intravenously in vivo to inhibit xenograft HNSCC tumor growth, without toxicity to the animal. The molecular pathway involved is independent of pAKT and complementary to cisplatin's mechanism of action. Thus, treatment of HNSCC with curcumin combined with cisplatin and/or an EGFR inhibitor such as cetuximab holds promise for development of clinical treatment protocols.
- Salivary analysis of oral cancer markers. Oral cavity carcinomas are in constant contact with saliva and thus shed characteristic proteins or tumor markers. We are collecting saliva samples from patients with oral cancers, for microarray analysis of such markers. Salivary analysis may provide a noninvasive and rapid method for detecting early primary or recurrent cancers.
- Treatment of oral cancers with curcumin. Patients who will be undergoing surgical resection of their HNSCC are being recruited for participation in a Phase 0/1 trial of oral curcumin. Pre-treatment biopsy specimens will be analyzed for IL-6, IL-8, and stem cell marker expression using immunohistochemistry. Patients will ingest oral curcumin tablets daily for 2 weeks prior to their surgery. Tissue from the surgical specimen will then be analyzed for changes in IL-6, IL-8, and stem cell marker expression, to determine if any changes have occurred after curcumin treatment.
- Stem cells in head and neck cancer. A specific population of tumor-initiating cells, or tumor stem cells, is responsible for the uncontrolled growth of cancers, as well as their resistance to chemotherapy and radiation. We have found that the population of CD44-positive cells within HNSCCs, when isolated, grows more quickly and is more resistant to cisplatin than CD44-negative cells. We are targeting HNSCC stem cells for treatment with curcumin, which because of its alternate mechanism of action compared to cisplatin, may inhibit growth of these stem cells.
- Curcumin suppression of head and neck cancer, NCI/NIH (grant #R21CA116826)
- Liposomal curcumin in combination with cisplatin for suppression of head and neck cancer, UCLA Academic Senate
- Oral curcumin: salivary analysis of biomarkers, UCLA Academic Senate
- Principal Investigators: Marilene B. Wang, MD; Eri S. Srivatsan, PhD
- Senior Advisors:
David Gjertson, PhD, Professor, Departments of Biostatistics, Pathology, and Laboratory Medicine
Chi Lai, MD, Assistant Professor, Department of Pathology and Laboratory Medicine
David Wong, DMD, DM Sc., Professor, Associate Dean of Research, UCLA Dental Research Institute
- Post Grad Research Fellows: M.S. Veena, PhD; Saroj Basek, PhD
- Graduate Students: Grace Kim, Eugene Han
- Visiting Students: Reason Wilken
- Namazie, A., Alavi, S., Olopade, O.I., Pauletti, G., Aghamohammadi, N., Aghamohammadi M., Gornbein, J.A., Calcaterra, T.C., Slamon, D.J., Wang, M.B., Srivatsan, E.S. Cyclin D1 amplification and p16 (MTS1/CDK4I) deletion correlate with poor prognosis in head and neck tumors. Laryngoscope 112:472-481, 2002.
- Lee, N.J., Wang, S.J., Durairaj, K.K., Srivatsan E.S., Wang, M.B. Increased expression of TGF-?1, ?-FGF, and ?-FGF in fetal as compared to adult fibroblast cell lines. Laryngoscope 110:616-619, 2000.
- Wang S.J., Mintz L.E., Venketesan N., Lee N.J., Srivatsan E.S., Wang M.B. Antisense cyclin D1 inhibits growth of head and neck cancer xenografts in nude mice. Third place award, resident basic science research, Association for Research in Otolaryngology, Academy of Otolaryngology--Head and Neck Surgery, Otolaryngol Head Neck Surg 124:656-662, 2001.
- Wang M.B., Yip, H.T., Srivatsan E.S. Antisense cyclin D1 enhances sensitivity of head and neck cancer cells to cisplatin. Laryngoscope 111: 982-988, 2001.
- Wang S.J., Wang M.B., Calcaterra, T.C. Combined radiotherapy with planned neck dissection for small head and neck cancers with advanced cervical metastases. Laryngoscope 110: 1794-1797, 2000.
- Azizzadeh B., Yip H.T., Blackwell K.E., Horvath S., Calcaterra T.C., Buga G.M., Ignarro L.J., Wang M.B. Nitric Oxide improves cisplatin cytotoxicity in head and neck squamous cell carcinoma. The Laryngoscope 111:1896-900, 2001.
- Namazie, A., Alavi, S., Aghamohammadi, N., Aghamohammadi, M., Calcaterra, T.C., Wang, M.B., Srivatsan, E.S. Fluorescence in situ hybridization for detecting p16 (MTS1/CDK4I) gene deletions in squamous cell carcinoma of the head and neck. Cancer Genetics and Cytogenetics 141:49-55, 2003.
- LoTempio, M.M., Veena, M.S., Steele, H.L., Ramamurthy, B., Ramalingam, T.S., Cohen, A.N., Chakrabarti, R., Srivatsan, E.S., Wang, M.B. Curcumin suppresses growth of head and neck squamous cell carcinoma, Clin Cancer Res 11: 6994-7002, 2005.
- Yip, H.T., Chopra, R., Chakrabarti R., Veena M.S., Ramamurthy, B., Srivatsan, E.S., Wang, M.B. Cisplatin induced growth arrest of head and neck cancer cells correlates with increased expression of p16 and p53. Arch Otolaryngol Head Neck Surg 132:317-326, 2006.
- Wang, D., Veena, M.S., Stevenson, K., Tang C., Ho, B., Mehta, K., Srivatsan, E.S., Wang, M.B. Liposome encapsulated curcumin suppresses growth of HNSCC in vitro and in xenografts through the inhibition of NFkB by an AKT independent pathway. Clinical Cancer Research, 14:6228-6236, 2008.
- Cohen, A.N., Veena M.S., Srivatsan E.S., Wang, M.B. Curcumin Suppresses IL-6 and IL-8 Production in Head and Neck Cancer Cells via Inhibition of Iκβ kinase (IKK). Archives of Otolaryngology-Head and Neck Surgery, 135: 190-197, 2009.
- Duarte, V.M., Han, E., Veena, M.S., Salvada A, Suh, J.D., Liang, L., Faull, K., Srivatsan E.S., Wang, M.B. Curcumin enhances the effect of cisplatin in suppression of head and neck squamous cell carcinoma via inhibition of IKKβ protein of the nuclear factor kB pathway, Clinical Cancer Research, submitted.