Nur Mohammad Monsur Hassan

Antitumor Effect of Temsirolimus against Oral Squamous Cell Carcinoma Associated with Bone Destruction

The mammalian target of rapamycin (mTOR) is engaged in the molecular pathogenesis of oral squamous cell carcinoma, which frequently invades the maxilla or the mandible. However, the effects of a mTOR inhibitor on bone destruction associated with oral squamous cell carcinoma are still unclear. In this study, we investigated the antitumor effect of temsirolimus-mediated mTOR inhibition against advanced oral squamous cell carcinoma. Temsirolimus inhibited the proliferation and migration of HSC-2 oral squamous cell carcinoma cells in vitro and suppressed the growth of oral squamous cell carcinoma xenografts in vivo. Significantly, we clearly show that temsirolimus inhibited osteoclast formation both in vitro and in vivo. Reverse transcriptase-PCR analysis showed that temsirolimus decreased the mRNA expression of receptor activator for nuclear factor-κB ligand, known as an osteoclast differentiation factor in bone stromal ST2 cells. Moreover, temsirolimus normalized blood-free calcium concentration in mouse models for humoral hypercalcemia. These findings suggest that mTOR signaling is a potential target of oral squamous cell carcinoma associated with bone destruction, and hence we describe the efficacy of temsirolimus for the treatment of advanced oral squamous carcinoma. Mol Cancer Ther; 9(11); 2960–9. ©2010 AACR.

DKK3 overexpression increases the malignant properties of head and neck squamous cell carcinoma cells

DKK3, a member of the dickkopf Wnt signaling pathway inhibitor family, is believed to be a tumor suppressor because of its reduced expression in cancer cells. However, our previous studies have revealed that DKK3 expression is predominantly observed in head and neck/oral squamous cell carcinoma (HNSCC/OSCC). Interestingly, HNSCC/OSCC patients with DKK3 expression showed a high rate of metastasis and poorer survival, and siRNA-mediated knockdown of DKK3 in HNSCC-derived cancer cell lines resulted in reduced cellular migration and invasion. From these data, it was hypothesized that DKK3 might exert an oncogenic function specific to HNSCC. In the present research, the DKK3 overexpression model was established, and its influences were investigated, together with molecular mechanism studies. The DKK3 expression profile in cancer cell lines was investigated, including HNSCC/OSCC, esophageal, gastric, colorectal, pancreatic, prostatic, and lung cancers. DKK3 overexpression was performed in HNSCC-derived cells by transfection of expression plasmid. The effects of DKK3 overexpression were assessed on cellular proliferation, migration, invasion, and in vivo tumor growth. The molecular mechanism of DKK3 overexpression was investigated by Western blotting and microarray analysis. DKK3 overexpression significantly elevated cellular proliferation, migration, and invasion, as well as increased mRNA expression of cyclin D1 and c-myc. However, reporter assays did not show TCF/LEF activation, suggesting that the increased malignant property of cancer cells was not driven by the Wnt/β-catenin pathway. For the investigation of the pathways/molecules in DKK3-mediated signals, the Western blot analyses revealed that phosphorylation of Akt (S473) and c-Jun (Ser63) was elevated. The application of a PI3K kinase inhibitor, LY294002, on HSC-3 DKK3 cells significantly decreased tumor cell proliferation, migration, and invasion. From these results, we demonstrated that DKK3 might contribute to cellular proliferation, invasion, migration, and tumor cell survival in HNSCC cells through a mechanism other than the canonical Wnt signaling pathway, which might be attributed to PI3K-Akt signaling.

Risk factors for dental caries among children with cerebral palsy in a low-resource setting.

To describe the oral health status and investigate factors affecting dental caries experience among children with cerebral palsy (CP) in rural Bangladesh.

Undergraduate dental students’ perceptions of head and neck anatomy teaching in Australia

INTRODUCTION Most Australian universities have abbreviated the anatomy curriculum and modified its mode of delivery. This study examines dental student perceptions of different methods of head and neck anatomy teaching with respect to the adequacy of allocated time and the relative meaningfulness of the teaching methods. METHODS All second-year students in the School of Dentistry and Health Sciences at Charles Sturt University (CSU) were invited to complete a matrix-grid questionnaire. Participants were asked to score four methods of teaching (lectures, study of prosected materials, tutorials and quizzes) using a 5-point Likert scale. The questionnaire included questions about the time adequacy for anatomy lectures, tutorials and laboratory study, and the potential value of learning anatomy through the study of prosected materials. SPSS (Version 21.0) was used to analyse the data, and statistical significance was set at 0.05. RESULTS Seventy-two students (79.5%) responded to the survey. Overall, learning anatomy through the study of prosected materials was the single highest scored method, followed by lectures, tutorials and quizzes. Graduate entrants felt that not enough time was devoted to learning anatomy through the study of prosected materials, compared with school leavers (89.4% and 10.6%, respectively), having one extra session of learning in the anatomy laboratory (71.4% and 28.6%, respectively) and adding dissection (75.0% and 25.0%, respectively) would be helpful. CONCLUSION This study demonstrates that dental students perceive the study of prosected materials in the wet laboratory as the most valuable method of learning anatomy, but an extended anatomy curriculum would be even more effective and appreciated.

p53 Mutation and Multiple Primary Oral Squamous Cell Carcinomas

Oral squamous cell carcinoma (OSCC) is a worldwide malignancy and is ranked the sixth most common cancer. At current rates, approximately 45,000 cases in the United States and more than 650,000 cases worldwide will be diagnosed each year (Jemel et al., 2008). One promising strategy for the treatment of OSCC and other cancers, which has developed as a result of breakthroughs in the fields of molecular biology, cancer genetics, and cancer biology, is molecular targeted therapy. Patients with a head-and-neck squamous cell carcinoma (HNSCC) often develop multiple malignant lesions. The oral sites that give rise to the majority of HNSCCs undergo cornification and shed squames during terminal differentiation, a process that is impaired in malignancies. The lymph nodes of the head and neck region form the principle site of primary metastasis, and perineural invasion marks tumours with a poor prognosis. Genetic changes correlate with lymph node metastasis in SCC. It is frequently observed that genetic damage persists beyond the histological border of precancerous lesions and tumours often develop far from the precancerous site (Braakhuis et al., 2003).

Ameloblastic fibro-odontoma in a 9-year-old boy

Ameloblastic fibro-odontoma (AFO) is a rare, benign mixed odontogenic tumor. A 9-year-old Japanese boy was referred to Okayama University Hospital in December 2013 for the evaluation of an unerupted tooth in his right lower mandible. A panoramic radiograph showed a well-defined multilocular radiolucent lesion extending from the right first molar to the ramus of the mandibular, containing radiopaque foci. The first molar was impacted by the lesion. The tumor was easily enucleated from the cortical bone, and the follicle of the first molar was removed. The first molar was preserved in the hope that it would erupt to the occlusal plane. At the 3-year follow-up there was no evidence of recurrence, and the right first molar had erupted to the occlusal plane.

Lactate Transporter Monocarboxylate Transporter 4 Induces Bone Pain in Head and Neck Squamous Cell Carcinoma

Head and neck squamous cell carcinoma (HNSCC) poses a significant challenge clinically, as it can invade facial bones and cause bone pain that is undertreated and poorly understood. Here we studied HNSCC bone pain (HNSCC-BP) in an intratibial mouse xenograft model that uses a human HNSCC cell line (SAS cells). These mice develop HNSCC-BP associated with an upregulation of phosphorylated ERK1/2 (pERK1/2), which is a molecular indicator of neuron excitation in the dorsal root ganglia (DRGs) of sensory nerve cell bodies. Our experiments demonstrated that the inhibition of monocarboxylate transporter 4 (MCT4) by short hairpin (shRNA) transduction suppressed the HNSCC-BP, the lactate level in bone marrow, and the pERK1/2 expression in DRG. The sensory nerves also expressed increased levels of the acid-sensing receptor TRPV1. DRG neurons co-cultured with SAS cells showed increased neurite outgrowth, and were inhibited by MCT4 silencing with shRNA. Collectively, our results show that HNSCC induced an acidic bone microenvironment that evokes HNSCC-BP via MCT4 expression.

Oral Disease and Malnutrition in the Elderly—Impact of Oral Cancer

Purpose of ReviewThe purpose of this paper is to review current evidence for a concomitant relationship between oral diseases and malnutrition in the elderly. A narrative overview of current literature was undertaken to combine the context for research with critical elaboration and commentary.Recent FindingsOral disease is one of the most common public health issues worldwide with significant socio-economic impacts, and yet it is frequently neglected in public health policy. Epidemiologic studies show that oral disease frequently causes malnutrition in the elderly. In particular, malnutrition is associated with poor quality of life and poor efficacy of oncologic therapy in oral cancer patients.SummaryAs oral disease remains a major public health burden worldwide, it is of great importance to integrate oral health into the nutrition agenda via the Common Risk Factor Approach. As such the long-term sustainable strategy for global oral health should focus on health promotion and malnutrition prevention in the elderly.