Department of Oral Biology: Student Research and Publications
SYNERGISTIC EFFECTS OF THE COMBINATION OF ERLOTINIB & EXO2 ON HEAD AND NECK CANCERMore than 90% of head and neck cancer is head and neck squamous cell carcinoma1 (HNSCC). Currently, the treatment involves modern surgery, conventional chemotherapy, and radiation. However, targeting, the epidermal growth factor receptor (EGFR) has been shown to prove advantageous for patient survival. EGFR activation leads to cell cycle progression. Blocking the EGFR by an antibody results in the inhibition of the receptor, therefore inhibition of cell proliferation. This makes EGFR a prime target for anticancer therapy, specifically with tyrosine kinase inhibitors being looked at as a possible form of inhibition. The goal of this project was to hopefully use small molecule inhibitor EXO2 and an EGFR specific tyrosine kinase inhibitor, Erlotinib, in a synergistic manner to fight against HNSCC. This study was done using cell cultures, MTT assay�s and western blot techniques, with cell cultures being done using the H6 cell line. The results from this study were found to be a preliminary success and will pave the way for future experiments in this area.
SERUM-C TERMINAL CROSSLINKING TELOPEPTIDE (CTX) AS A PREDICTIVE BIOMARKER OF BISPHOSPHONATE-RELATED OSTEONECROSIS OF JAW (BRONJ): SYSTEMATIC REVIEW AND META-ANALYSISThe aim of this systematic review was to evaluate the validity of using preoperative serum C-terminal crosslinking telopeptide (CTX) levels as predictive factor of increased risk of developing medication-related osteonecrosis of the jaw (MRONJ) in patients on bisphosphonate (BP) therapy who undergo invasive dental procedures. A search was conducted through PubMed, MEDLINE, and Web of Science, following PRISMA guidelines and the Cochrane Handbook for Systematic Reviews of Interventions. Meta-analysis was conducted on the risk ratio. The methodological index for nonrandomized studies (MINORS) and Quality Appraisal of Reliability Studies (QAREL) checklist were used to assess quality. Eighteen clinical trials, involving 2301 patients were included. Most patients received Alendronate or Risedronate for an average of 62.14 months. The average serum CTX level in BP-treated patients before surgery was 217.67 pg/ml. Meta-analysis demonstrated that the cutoff in CTX level (150 pg/ml) was not predictive of BRONJ risk. The sensitivity of CTX value <150 pg/ml was 34.26% and the specificity was 77.08%. The use of CTX to diagnose BRONJ risk following dental procedures in bisphosphonate-treated patients is not justified. Further studies are needed to develop other reliable biomarkers.
Histology of the Dental Extraction Sites of Bisphosphonate Treated RatsBisphosphonate is a drug given to both men and women who are experiencing decreasing bone density and strength. When patients taking bisphosphonate undergo some sort of jaw trauma (i.e. tooth extraction, accident), they can experience necrosis or cell death of the jawbone. Our hypothesis is that bisphosphonate molecules bound to the bone matrix contribute to bone necrosis. For my thesis, a histological analysis of the mandibles from bisphosphonate treated rats after dental extraction with and without removal of bisphosphonates from the extraction site of the bone was done. Histological sections of the jaw from bisphosphonate treated rats after bilateral extraction of the first and second molar teeth were taken. On one side, the extraction site was treated with EDTA to chelate bisphosphonates from the bony wall of the tooth socket. The other side of the rat’s jaw was treated with Saline. I then evaluated the vitality of alveolar bone by counting the number of dead versus live osteocytes around the extraction site and comparing the ratios between the chelated and un-chelated sides from each rat. The study determined whether removal of localized bisphosphonates is beneficial to preserve bone vitality after dental extraction. As expected, the percentage of live osteocytes decreased in the alveolar bone of animals treated with Zoledronate (ZA), a strong dose of bisphosphonate. Furthermore, there was a trend of increased percentage of live cells when EDTA was used, although the differences were not statistically significant. These results support other studies in our laboratory that have shown that localized bisphosphonates play a role in the osteonecrosis associated with ZA treatment. It, therefore, provides evidence that localized bisphosphonates contribute to the etiology of bone necrosis in patients undergoing bisphosphonate treatment.