Anak Iamaroon

Epithelial-Mesenchymal Transition in Oral Squamous Cell Carcinoma

Oral cancer is one of the drastic human cancers due to its aggressiveness and high mortality rate. Of all oral cancers, squamous cell carcinoma is the most common accounting for more than 90%. Epithelial-mesenchymal transition (EMT) is suggested to play an important role during cancer invasion and metastasis. Recently, emerging knowledge on EMT in carcinogenesis is explosive, tempting us to analyze previous studies on EMT in oral squamous cell carcinoma (OSCC). In this paper, we have first addressed the general molecular mechanisms of EMT, evidenced by alterations of cell morphology during EMT, the presence of cadherin switching, turning on and turning off of many specific genes, the activation of various signaling pathways, and so on. The remaining part of this paper will focus on recent findings of the investigations of EMT on OSCC. These include the evidence of EMT taking place in OSCC and the signaling pathways employed by OSCC cells during their invasion and metastasis. Collectively, with the large body of new knowledge on EMT in OSCC elaborated here, we are hopeful that targeting treatment for OSCC will be developed.

Overexpression and activation of Akt2 protein in oral squamous cell carcinoma

Aberrations of signal transducers in PI3K/Akt pathway have been found in many human cancers, and may play a critical role in carcinogenesis. Advanced research on oral cancer treatments, using novel agents targeting the PI3K/Akt signaling pathway, is being investigated with promising results. The objectives of this study were (1) to investigate expression of pan-Akt and its phosphorylated form (p-Akt), Akt1, and Akt2 in oral squamous cell carcinoma (OSCC) specimens (n=20) by immunohistochemistry, and (2) to determine mRNA expression of three Akt isoforms, including Akt1, Akt2, and Akt3, as well as their respective proteins, in five oral cancer cell lines and normal human oral keratinocytes (HOKs) by RT-PCR and Western blot assays. The results show that pan-Akt was expressed in 80% of OSCC cases, while Akt1, Akt2, and p-Akt were expressed in all OSCC cases. An intense expression of p-Akt at the invasive fronts of some OSCC samples was observed. Consistent with the immunohistochemical findings, p-Akt and Akt2 were overexpressed in all oral cancer cell lines in comparison with HOKs, whereas Akt2 mRNA was constitutively expressed, suggesting post-transcriptional regulation. In contrast, Akt1 mRNA and protein were constitutively expressed in all oral cancer cell lines and HOKs, while Akt3 mRNA appeared to be minimally expressed. In summary, these findings demonstrate that Akt2 and p-Akt are overexpressed in OSCC and may be involved in carcinogenesis, and suggest that post-transcriptional modification of Akt2 in OSCC may occur.

Enamel-renal-gingival syndrome and FAM20A mutations

The enamel‐renal syndrome of amelogenesis imperfecta (AI) and nephrocalcinosis, and the amelogenesis imperfecta‐gingival fibromatosis syndrome have both been associated with mutations in FAM20A. We report on two unrelated Thai patients with three novel and one previously reported mutations in FAM20A with findings suggesting both disorders, including hypoplastic AI, gingival fibromatosis, unerupted teeth, aggressive periodontitis, and nephrocalcinosis/nephrolithiasis. Additional findings consisted of a supernumerary premolar, localized aggressive periodontitis, thin alveolar bone, vitamin D deficiency‐associated hyperparathyroidism, and heterotopic calcification in other tissues, including lungs, dental pulp, gingiva, dental follicles, and periodontal tissues, and early cessation of limited menstruation. Greater promotory activity of urine on calcium oxalate crystal growth compared to controls may help to explain the pathogenesis, and suggest that FAM20A mutations can contribute to nephrocalcinosis/nephrolithiasis. Our findings expand the phenotypic spectrum of FAM20A mutations. Since both of our patients and a large number of previously reported cases had all the important features of both syndromes, including AI, renal anomalies, and gingival fibromatosis, we are convinced that these two disorders actually are the same entity. The name of enamel‐renal‐gingival syndrome is suggested.

Ten-year analysis of oral cancer focusing on young people in northern Thailand

The objective of the present study was to assess the current situation of oral squamous cell carcinoma (OSCC) in northern Thailand, with an emphasis on patients <40 years of age. Medical records of patients histologically diagnosed with OSCC were collected from the Cancer Registry of Maharaj Nakorn Chiang Mai Hospital, Thailand between 2001 and 2010. The clinico-demographic data of patients aged <40 years (young group) and those aged ≥40 years (old group) were compared. A total of 874 patients were included in this study, of which 4.1% were <40 years of age. The tongue was the most common cancer site in both age groups. Most patients in both age groups were diagnosed with oral cancer at stage IV. Tobacco smoking (62.3%) and alcohol consumption (52.3%) were the most common risk factors in both age groups. However, the rates of betel quid chewing (17.5%) had decreased from those found in our study in the previous decade (50.2%); these rates were not found in the young group. The 5-year survival rate was 27.4% for the old group and 56.2% for the young group. OSCC remains a serious oral health problem in northern Thailand, and it has not been resolved among young adults.

Roles of Human Papillomaviruses and p16 in Oral Cancer

Head and neck cancer, including oral cancer, is the sixth most common cancer in humans worldwide. More than 90% of oral cancers are of squamous cell carcinoma type. Recent studies have shown a strong relationship between human papillomavirus (HPV) infection and head and neck cancer, especially oropharyngeal squamous cell carcinoma (OPSCC) and oral squamous cell carcinoma (OSCC). Moreover, the incidence of HPV-related OSCC appears to be on the rise while HPV-unrelated OSCC tends to have stabilized in the past decades. p16, a tumor suppressor gene, normally functions as a regulator of the cell cycle. Upon infection with high-risk types of HPV (HR-HPV), particularly types 16, 18, 31, 33, 34, 35, 39, 51, 52, 56, 58, 59, 66, 68, and 70, the expression of p16 is aberrantly overexpressed. Therefore, the expression of p16 is widely used as a surrogate marker for HPV infection in head and neck cancer.

New prediction models for dental age estimation in Thai children and adolescents

UNLABELLED The aims of this study were to develop new prediction models for dental age estimation and to test the accuracy of the resulting models in comparison with the Demirjian et al. and the Willems et al. methods in Thai children and adolescents. Digital panoramic radiographs of 1,134 Thai individuals (487 males and 647 females) aged from 6 to 15 years were selected and evaluated for dental age estimation. Quadratic regression was used to generate new models. The results showed that the new prediction models indicated a strong correlation coefficient between the dental maturity score and the chronological age in both sexes (r=0.951 for males, r=0.945 for females). The new age prediction models were: y=0.006297x(2) - 0.804930x+32.591843 for males and y=0.010677x(2) - 1.538823x+61.955056 for females, where y is the dental age, x is the dental maturity score according to Demirjian et al. METHOD Moreover, these new models were tested showing the greatest accuracy for estimating the age in Thai samples using the mean difference values between the dental and the chronological ages (-0.04 years for males, 0.02 years for females) when compared with the Demirjian et al. and the Willems et al. METHODS In addition, the new models revealed a high percentage of accuracy in the absolute difference values between the dental and the chronological ages within 1 year (76.26% and 74.49% for males and females, respectively). Furthermore, our results in mean difference values indicated that the Demirjian et al. method (0.11 and 0.10 years for males and females, respectively) was more accurate than the Willems et al. method (-0.37 and -0.39 years for males and females, respectively) in Thai samples. In conclusion, the new age prediction models in this study provide accurate age estimation in both sexes, suggesting that these models be applied for forensic age estimation, especially in Thai children and adolescents.

Increased cyclooxygenase 2 expression in association with oral lichen planus severity

Background/purpose Although some studies have shown induction of cyclooxygenase 2 (COX-2) in oral lichen planus (OLP), an association between COX-2 upregulation and OLP clinical severity has not been investigated. Therefore, we aimed to compare COX-2 expression in OLP with that in normal oral tissues, and to determine correlations between COX-2 expression and both clinical criteria and visual analog scale (VAS) scores. Materials and methods COX-2 expression was studied in 25 OLP and 13 normal oral tissues by immunohistochemistry. Both clinical criteria and VAS scores were used to evaluate the clinical severity of OLP. The differences in COX-2 expression between OLP and normal tissues, and the correlations between COX-2 expression and clinical severity were determined by the nonparametric statistical tests. Results COX-2 expression was significantly increased in OLP epithelium when compared with normal epithelium (P < 0.001), and intense COX-2 staining in inflammatory infiltrates was observed in the OLP lamina propria. COX-2 expression in OLP epithelium and inflammatory infiltrates was significantly correlated with the clinical criteria score (r = 0.428, P = 0.007, and r = 0.681, P < 0.001, respectively), whereas a significant correlation with the VAS score was observed only in OLP inflammatory infiltrates (r = 0.605, P < 0.001). Conclusion Enhanced COX-2 expression in both OLP epithelium and inflammatory infiltrates correlates well with the clinical severity. An association between VAS score and COX-2 expression in OLP inflammatory infiltrates suggests an important role of additional COX-2 expression from inflammation in causing pain in OLP patients.

Akt2 and p-Akt overexpression in oral cancer cells is due to a reduced rate of protein degradation.

OBJECTIVE To quantitatively measure the increased expression of Akt2 and its phosphorylated form (p-Akt) in oral cancer cell lines and investigate the post-translational mechanism for Akt2 and p-Akt overexpression. METHODS Three oral cancer cell lines and three cell lines of primary human oral keratinocytes (HOKs) were cultured and the degrees of Akt2 and p-Akt expression was evaluated by immunoblot analysis and flow cytometry. Each cell line was incubated with cycloheximide, an inhibitor of new protein synthesis, for various times to quantitatively determine the remaining expression levels of Akt2 and p-Akt by flow cytometry. The localization of Akt2 and p-Akt was assessed by immunofluorescence. RESULTS The levels of Akt2 and p-Akt proteins were significantly higher in cancer cell lines than those in HOKs (P < 0.05). When the new protein synthesis was blocked by cycloheximide treatment, the degradation rate of Akt2 and p-Akt in oral cancer cells was significantly lower than that in HOKs (P < 0.05). Both Akt2 and p-Akt were more intensely stained in the cytoplasm of cancer cells, whereas HOKs expressed Akt2 and p-Akt only minimally. CONCLUSION Both Akt2 and p-Akt were overexpressed in oral cancer cells, which may be partly explained by a reduced rate of protein degradation in order to maintain high cytosolic levels.

Cutis laxa with pulmonary emphysema, conjunctivochalasis, nasolacrimal duct obstruction, abnormal hair, and a novel FBLN5 mutation

We report on a 4‐year‐old girl with autosomal recessive cutis laxa, type IA, or pulmonary emphysema type (ARCL1A; OMIM #219100), with loose and wrinkled skin, mitral and tricuspid valve prolapse, conjunctivochalasis, obstructed nasolacrimal ducts, hypoplastic maxilla, and early childhood‐onset pulmonary emphysema. Mutation analysis of FBLN5 showed a homozygous c.432C>G missense mutation, and heterozygosity in the parents. This is predicted to cause amino acid substitution p.Cys144Trp. Conjunctivochalasis or redundant folds of conjunctiva and obstructed nasolacrimal ducts have not been reported to be associated with FBLN5 mutations. Histopathological study of the conjunctival biopsy showed that most blood vessels had normal elastic fibers. The gingiva appeared normal, but histologically elastic fibers were defective. Scanning electron micrography of scalp hair demonstrated hypoplastic hair follicles. The cuticles appear intact underneath the filamentous meshwork.

Saliva-Based Screening of High-Risk Human Papillomavirus Strains: Detection in Female Indonesian and Thai Dental Students.

BACKGROUND Currently it is believed that human papillomaviruses (HPV) are associated with the development of some oral/oropharyngeal cancers. It has been suggested that these viruses influence carcinogenesis in both smokers and non-smokers. Data on the prevalence of HPV in healthy adults are thus needed to estimate the risk of oral/oropharyngeal cancer. The aim of this study was to assess the prevalence of oral HPV in healthy female adults in Indonesia and Thailand. MATERIALS AND METHODS Healthy female students from the Faculties of Dentistry of Universitas Indonesia and Chiang Mai University were asked to participate in this pilot study. DNA was extracted from saliva specimens and screened for HPV16 and HPV18 using PCR. RESULTS The age, marital status and sexual experience of the subjects between the two countries were not significantly different. Eight (4%) and 4 (2%) samples were positive for HPV16 and HPV18, respectively. Fishers Exact test found a significant difference between HPV16 positivity in subjects who were married and had sexual intercourse but not for HPV18. CONCLUSIONS This study successfully detected presence of HPV16 and HPV18 DNA in a number of saliva samples from female dental school students. Marital status, experience of sexual intercourse and safe sexual practice are related to the possibility of finding HPV DNA finding in saliva. Dentists, physicians and other health care professionals may gain significant value from the findings of this study, which provide an understanding of the nature of HPV infection and its risk to patient health and disease.