MATERIALS AND METHODS: A survey on dentists' knowledge and their practices in prevention and early detection of oral cancer was conducted using a 26-item self-administered questionnaire.
RESULTS AND CONCLUSIONS: A response rate of 41.7% was achieved. The level of knowledge on early signs and risk habits associated with oral cancer was high and the majority reported to have conducted opportunistic screening and advised patients on risk habit cessation. Factors that influenced the dentist in practising prevention and early detection of oral cancer were continuous education on oral cancer, age, nature of practice and recent graduation. Notably, dentists were receptive to further training in the area of oral cancer detection and cessation of risk habits. Taken together, the study demonstrated that the dental clinic is a good avenue to conduct programs on opportunistic screening, and continuous education in these areas is necessary to adequately equip dentists in running these programs. Further, this study also highlighted knowledge deficits and practice shortcomings which will help in planning and developing programs that further encourage better participation of dentists in prevention and early detection of oral cancer.
METHODS: Baseline awareness and impact of the campaign was measured using self-administered questionnaires sent via email to individuals. The campaign was aired on two national television channels and the reach was monitored through an independent programme monitoring system.
RESULTS: 78.2% of respondents had heard of oral cancer, and this increased significantly after the campaign. However, the ability to recognize signs and symptoms remains unchanged. We found that the level of awareness differed between the distinct ethnic subgroups and the reach of the campaign was not uniform across all ethnicities.
CONCLUSION: This substantial study to measure the oral cancer awareness in Malaysia provides important baseline data for the planning of public health policies. Despite encouraging evidence that a mass media campaign could increase the awareness of oral cancer, further research is required to address the acceptability, comprehensiveness and effectiveness. Furthermore, different campaign approaches may be required for specific ethnic groups in a multi-ethnic country such as Malaysia.
RESULTS: We developed DeSigN, a web-based tool for predicting drug efficacy against cancer cell lines using gene expression patterns. The algorithm correlates phenotype-specific gene signatures derived from differentially expressed genes with pre-defined gene expression profiles associated with drug response data (IC50) from 140 drugs. DeSigN successfully predicted the right drug sensitivity outcome in four published GEO studies. Additionally, it predicted bosutinib, a Src/Abl kinase inhibitor, as a sensitive inhibitor for oral squamous cell carcinoma (OSCC) cell lines. In vitro validation of bosutinib in OSCC cell lines demonstrated that indeed, these cell lines were sensitive to bosutinib with IC50 of 0.8-1.2 μM. As further confirmation, we demonstrated experimentally that bosutinib has anti-proliferative activity in OSCC cell lines, demonstrating that DeSigN was able to robustly predict drug that could be beneficial for tumour control.
CONCLUSIONS: DeSigN is a robust method that is useful for the identification of candidate drugs using an input gene signature obtained from gene expression analysis. This user-friendly platform could be used to identify drugs with unanticipated efficacy against cancer cell lines of interest, and therefore could be used for the repurposing of drugs, thus improving the efficiency of drug development.
Methods: The effect of palbociclib was evaluated in a panel of well-characterized OSCC cell lines by cell proliferation assays and further confirmed by in vivo evaluation in xenograft models. PIK3CA-mutant isogenic cell lines were used to investigate the effect of PIK3CA mutation towards palbociclib response.
Results: We demonstrated that 80% of OSCC cell lines are sensitive to palbociclib at sub-micromolar concentrations. Consistently, palbociclib was effective in controlling tumor growth in mice. We identified that palbociclib-resistant cells harbored mutations in PIK3CA. Using isogenic cell lines, we showed that PIK3CA mutant cells are less responsive to palbociclib as compared to wild-type cells with concurrent upregulation of CDK2 and cyclin E1 protein levels. We further demonstrated that the combination of a PI3K/mTOR inhibitor (PF-04691502) and palbociclib completely controlled tumor growth in mice.
Conclusions: This study demonstrated the potency of palbociclib in OSCC models and provides a rationale for the inclusion of PIK3CA testing in the clinical evaluation of CDK4/6 inhibitors and suggests combination approaches for further clinical studies.
SIGNIFICANCE: Mutant HRAS drives metastasis of head and neck cancer by switching off the Hippo pathway to activate the YAP1-AXL axis and to stimulate lymphovascular angiogenesis.
SIGNIFICANCE: NPC268 is the first and only EBV-positive cell line derived from a primary non-keratinizing, differentiated nasopharyngeal carcinoma, an understudied but important subtype in Southeast Asian countries. This model adds to the limited number of authentic EBV-positive lines globally that will facilitate mechanistic studies and drug development for NPC.
METHODS: The expression of IFITM3 in OSCC and normal oral mucosal tissues was assessed by qRT-PCR and immunohistochemistry. The role of IFITM3 in driving OSCC cell proliferation and survival was examined using siRNA-mediated gene knockdown, and the role of IFITM3 in driving cell cycle regulators was examined using Western blotting.
RESULTS: We found that IFITM3 is overexpressed in more than 79% of primary OSCCs. We also found that IFITM3 knockdown led to impaired OSCC cell growth through inhibition of cell proliferation, induction of cell cycle arrest, senescence and apoptosis. In addition, we found that IFITM3 knockdown led to reduced expressions of CCND1 and CDK4 and reduced RB phosphorylation, leading to inhibition of OSCC cell growth. This information may be instrumental for the design of novel targeted therapeutic strategies.
CONCLUSIONS: From our data we conclude that IFITM3 is overexpressed in OSCC and may regulate the CCND1-CDK4/6-pRB axis to mediate OSCC cell growth.
METHODS: Dentists were recruited through two main dental associations in Malaysia and attended a 1-day training session on recognizing abnormalities within the oral cavity. Following the training, the dentists conducted screening and provided risk habits cessation advice at their respective clinics for 6 months. The impact of the program was evaluated by determining the number of patients who were screened and/or provided with risk habits cessation advice.
RESULTS: Twenty-six dentists took part in the program and conducted opportunistic screening on a total of 2603 individuals. On average, they screened about 23.0% of their patients and 5.1% were given risk habits cessation advice. Notably, dentists who had lower patient load were more likely to conduct opportunistic screening.
CONCLUSIONS: While the participating private dentists state that they have a role in performing opportunistic screening and providing risk habits cessation advice, these activities are still not a priority area in the private clinics, strongly suggesting that strategies to motivate dentists in this setting are urgently needed.