OBJECTIVES: This study was performed to identify mechanisms of afatinib resistance and to explore potential afatinib-based combination treatments with other targeted inhibitors in oral squamous cell carcinoma.
METHODS: We determined the anti-proliferative effects of afatinib on a panel of oral squamous cell carcinoma cell lines using a crystal violet-growth inhibition assay, click-iT 5-ethynyl-2'-deoxyuridine staining, and cell-cycle analysis. Biochemical assays were performed to study the underlying mechanism of drug treatment as a single agent or in combination with the MEK inhibitor trametinib. We further evaluated and compared the anti-tumor effects of single agent and combined treatment by using oral squamous cell carcinoma xenograft models.
RESULTS: In this study, we showed that afatinib inhibited oral squamous cell carcinoma cell proliferation via cell-cycle arrest at the G0/G1 phase, and inhibited tumor growth in xenograft mouse models. Interestingly, we demonstrated reactivation of the mitogen-activated protein kinase (ERK1/2) pathway in vitro, which possibly reduced the effects of ErbB inhibition. Concomitant treatment of oral squamous cell carcinoma cells with afatinib and trametinib synergized the anti-tumor effects in oral squamous cell carcinoma-bearing mouse models.
CONCLUSIONS: Our findings provide insight into the molecular mechanism of resistance to afatinib and support further clinical evaluation into the combination of afatinib and MEK inhibition in the treatment of oral squamous cell carcinoma.
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: Six hemi-mandible samples were scanned using the i-CAT CBCT system. The scanned data was transferred to the OsiriX software for measurement protocol and subsequently into Mimics software to fabricate customized cutting jigs and 3D biomodels based on rapid prototyping technology. The hemi-mandibles were segmented into 5 dentoalveolar blocks using the customized jigs. Digital calliper was used to measure six distances surrounding the mandibular canal on each section. The same distances were measured on the corresponding cross-sectional OsiriX images and the 3D biomodels of each dentoalveolar block.
RESULTS: Statistically no significant difference was found when measurements from OsiriX images and 3D biomodels were compared to the "gold standard" -direct digital calliper measurement of the cadaveric dentoalveolar blocks. Moreover, the mean value difference of the various measurements between the different study components was also minimal.
CONCLUSION: Various distances surrounding the mandibular canal from 3D biomodels produced from the CBCT scanned data was similar to that of direct digital calliper measurements of the cadaveric specimens.
METHODS: Retrospective study of medical notes of craniosynostosis patients who attended the CFC in UMMC from 2014 to December 2020.
RESULTS: Out of 37 patients, 29 had syndromic craniosynostosis, and 8 had non-syndromic craniosynostosis. Visual impairment was present in 32.1% of patients. Causes for visual impairment were as follows - amblyopia (25.0%), exposure keratopathy (3.6%), and optic atrophy (3.6%). Hypermetropia and myopia were each seen in 20.6% of patients. Astigmatism was seen in 47.1% of patients, and 29.1% had anisometropia. Proptosis was present in 78.6% and lagophthalmos in 53.3% of patients. Strabismus in primary position occurred in 51.7% of patients. Thirty-one percent of the patients had exposure keratopathy. Optic disc atrophy was seen in 13.7% of patients, and 8.3% had optic disc swelling. Optic disc swelling was resolved in all patients who underwent craniofacial surgery.
CONCLUSION: Our experience in Malaysia was consistent with previously reported data on ophthalmic features of craniosynostosis patients. Additionally, we found that non-syndromic craniosynostosis patients are also at risk of ocular complications just as much as syndromic patients. Appropriate treatment of amblyogenic risk factors, ocular complications, and timely detection of papilledema, and prompt surgical intervention are crucial in preserving long-term visual function in these patients.
SUBJECTS AND METHODS: A prospective study of 355 participants, including 280 with oral lesions/variants was conducted. Adults aged ≥18 treated at tertiary referral centres were included. Images of the oral cavity were taken using MeMoSA®. The identification of the presence of lesion/variant and referral decision made using MeMoSA® were compared to clinical oral examination, using kappa statistics for intra-rater agreement. Sensitivity, specificity, concordance and F1 score were computed. Images were reviewed by an off-site specialist and inter-rater agreement was evaluated. Images from sequential clinical visits were compared to evaluate observable changes in the lesions.
RESULTS: Kappa values comparing MeMoSA® with clinical oral examination in detecting a lesion and referral decision was 0.604 and 0.892, respectively. Sensitivity and specificity for referral decision were 94.0% and 95.5%. Concordance and F1 score were 94.9% and 93.3%, respectively. Inter-rater agreement for a referral decision was 0.825. Progression or regression of lesions were systematically documented using MeMoSA®.
CONCLUSION: Referral decisions made through MeMoSA® is highly comparable to clinical examination demonstrating it is a reliable telemedicine tool to facilitate the identification of high-risk lesions for early management.