Procedures cannot be applied until they are uncovered, developed, and verified. 

 

Below are examples of our dedicated research team in the lab. 

A thumb nail sketch of the important research being performed at the Keck is described below.

Sphingosine kinase (SPK)

This project is designed to alter the metabolism of ceramide which makes squamous cells more sensitive to radiation. Ceramide is a sphingolipid metabolite and a critical component of ionizing radiation-induced apoptosis. Sphingosine 1-phosphate (S1P) is known as a tumor-promoting lipid, yet its signaling pathways are not fully understood. S1P has been shown to induce transient tyrosine phosphorylation of EGFR and c-Met in gastric cancer cells, both of which have been proposed as prognostic markers for gastric cancer. This indicates that S1P acts upstream of various receptor tyrosine kinases (RTKs) and thus may act as a potent stimulator of cancer cells. Sphingosine kinase (SPK) is the enzyme that converts sphingosine to S1P and it is believed to play an important role in promoting tumor growth. It is our goal to determine whether SPK inhibition affects the suppression of downstream pathways thought to integral in HNSCC progression and the relationship between SPK to clinical outcome.

         Our preliminary results have shown the higher expression of SPK in five HNSCC specimens. SPK expression was shown higher in advanced disease and metastatic lymph nodes. In bladder cancer cell line sphingosine kinase mediates VEGF-induced activation of Ras and mitogen-activated protein kinases (MAPK)(). These studies propose SPK is a potential therapeutic target for HNSCCs.

         We hypothesize: 1) That SPK expression correlates with HNSCC tumor grade, stage and survival.  2) That the expression of SPK will affect growth, migration, invasive and survival capabilities of HNSCC. 4) That specific inhibitors of SPK function can be developed and evaluated as potential therapies. 5) SPK has been implicated as an important component of radiation-induced apoptosis and the inhibition of SPK will induce increased susceptibility to radiation therapy. We propose to test these hypotheses with the ultimate hope that the results of these studies can be translated into realization of anti-S1P therapies for HNSCC and improved patient quality of life.

 Bio-ectrical Stimulation

Effective management of severe swallowing disorders requires preventive measures aimed at reducing tissue toxicity, whereas rehabilitative measures should focus on intensive early interventions. Existing treatments for dysphagia are unable to restore complete swallow function in patients with HNC. Physical maneuvers to compensate for the deficiency (such as tucking the chin and suck swallow) are considered generally ineffective. Thermal-tactile stimulation (i.e., application of cold to the anterior tonsillar pillar) and biofeedback have limited success rates. The other limitation of the current treatment modalities of dysphagia is lengthy therapy.

Electrical stimulation (ES) is another modality that has been used in a variety of structures including soft palate and neck has shown varying success. In the clinical setting, atrophic muscles have usually been stimulated transcutaneously by using large electrodes mounted temporarily on the skin. This approach has several undesirable features. High stimulus voltages and currents are required to overcome the high resistance of the skin and the long distance to the muscles. The contractions elicited by the stimulation are generally confined to superficial muscles, which tend to contain fast twitch, glycolytic and fatigable fiber types. The stimulation often produces unpleasant skin sensations and can cause skin irritation. The technology is tolerated by highly motivated adult patients or athletes who can understand its usefulness; it is often rejected by less compliant or less motivated patients.

BIONS area new class of generic wireless devises that can be injected into muscles and near nerves to deliver precisely metered stimulation pulses. These injectable, wireless micromodules receive power and command signals by inductive coupling from an external antenna (Cameron et al. 1997; Loeb et al. 1991; Loeb et al. 2001). Four generations of this technology are now either in clinical trials or under development. All are designed to stimulate myelinated sensory or motor axons, typically in peripheral nerves or muscles.

VitalStim

Existing treatments for dysphagia are unable to restore complete swallow function in patients with HNC. Physical maneuvers to treat dysphagia (such as tucking the chin and suck swallow) are considered generally ineffective (9). Thermal-tactile stimulation (i.e., application of cold to the anterior tonsillar pillar) and biofeedback have limited success rates (10). The other limitation of the current treatment modalities of dysphagia is lengthy therapy (11).

Neuromuscular Electrical Stimulation (NMES) designed to stimulate peripheral and sensory nerves is gradually becoming a recognized treatment option for neuro-rehabilitation. There is a growing scientific elucidation of clinical benefits of peripheral and central responses from NEMS (12). NMES has been used in a variety of structures including soft palate and neck and has shown varying success. Multiple factors are responsible for the inconsistent results in restoring swallow function using this strategy. A major factor is the time interval between onset of tissues injury and electrical stimulation. NMES is more effective when it is initiated early to prevent disuse muscle atrophy (13). Recently one method of NMES called VST has demonstrated consistently promising results in stroke patients with dysphagia and has obtained FDA clearance for treating dysphagia.

VitalStim Therapy: VST utilizes placement of surface electrodes on the anterior neck for transcutaneous stimulation of the extrinsic muscles of the larynx and the muscles of the base of tongue through specially designed surface electrodes. VST improves the oral and pharyngeal phases of swallowing. It also does not influence the process of wound healing and hence can be used early during the post operative period in HNC patients.

Lymphogenesis

Our preliminary results have shown that several tumor angiogenic factors (VEGF-A, VEGF-C, EphB4) and cytokine IL-8 were overexpressed in 5 of 5 HNSCC specimens. The observed trend is higher expression of these factors in samples with advanced metastatic lymph nodes. These factors appear to play a critical role in the cell survival and invasive behavior of HNSCC. The co-expression of certain markers like VEGF and IL-8 in HNSCC tumors has been associated with tumor growth and decreased survival (1). Lymph node studies have shown similar overexpression of VEGF-C and its receptor Flt-4 as well as CXCR4 (2-4). While there is an association between these angiogenic factors and lymph node metastases, we know of no research that has co-studied these factors in HNSCC specimens and the respective lymph node tissues. With these results, we will conduct a microarray on two patients with a large tumor and no lymph node and two patients with a small tumor and metastatic lymph node in order to study the role of these known genes, along with any new factors found, in lymph node metastases. Finally, those genes most potent for lymph node metastases will be targeted and inhibited.

We hypothesize: 1) That lymph node metastases and lymph node involvement in HNSCC is indicative of decreased patient survival. 2) That these early genes are prognostic markers and they are involved in lymph nodes metastases. 3) That among those genes listed, VEGF-C and Flt-4 will be overexpressed in the primary tumor and the lymph node. 4) That one or more of the known or unknown pro-angiogenic factors listed will be overexpressed and plays a role in lymph node metastases. 4) That specific inhibitors of those genes can be developed and evaluated as potential cancer therapeutics. We propose to test these hypotheses with the ultimate hope that the results of this study will enable the inhibition of lymph node metastases and an increase in the overall survival of patients with HNSCC.

(For more information concerning the research please use the contact form on this site to query us. We will respond immediately.)

 

Rigorous Application of Science

Used to Detect, Prevent, and Cure Head and Neck Cancer

The Mission of the researchers at the USC Keck School of Medicine is to further perfect early detection, prevention, and the development of novel therqpies.  They will continue to implement strategies employing state-of-the-art combinations of emerging technologies and established protocals, such as: Implementing proprietary micro- and nano- technologies to aid early identification of disease. Assessing cellular DNA to identify new markers of disease. Driving biomedical research to improve the function of the mouth for eating, speaking, and swallowing. Improving methods of radiation and chemotherapy to both enhance outcomes and reduce adverse effects. Developing vaccine therapies to reduce disease recurrence. Promoting outreach programs to drive educational efforts that will improve the profile of the disease.    The "Head and Neck Support Group" is dedicated to assisting the efforts of the Keck School of Medicine's efforts and will aid them to the best of our abilities.

 

 Our Enthusiam Know No Bounds....