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No description available.

Abstract A population-based study was conducted to determine the trends in incidence and survival of cancer of the mobile tongue in Finland over the past 40 years. Possible changes in patient and tumour characteristics, early detection and prognostic factors of cancer of the mobile tongue were monitored in a geographically defined area of Northern Finland over the past 20 years. There were 1504 new cases with cancer of the mobile tongue in 1953-1994 in Finland and 105 cases in 1974-1994 in Northern Finland. An increasing trend in incidence of cancer of the mobile tongue was observed over the past 20 years both nationwide and in Northern Finland. The stage distribution of the cancer of the mobile tongue remained very much the same throughout the study period. Despite the increasing incidence rate and unchanged stage distribution of the tumours, the 5-year relative survival rate of cancer of the tongue improved from 40% to 58% in the 40-year study period in Finland. To evaluate the detection of cancer of the tongue, patients' primary care files were reviewed. It was revealed that the diagnostic skills of the physician/dentist first contacted by the patient had a significant effect on the patient's prognosis. If the cancer was not detected at the primary visit and no follow-up was scheduled, the delay was often fatally long. The most important factor influencing the referral pattern was the patient's primary symptom at the initial visit. The more closely the symptom was related to the tongue, the more likely the patient was correctly referred. To recognise aggressively behaving early stage (Stages I-II) cancers of the tongue, various prognostic factors were analysed. It was observed that an old age (65+years) of the patient, a high malignancy score of the tumour and the absence of p53 predicted poor prognosis in early stage carcinomas. Patients with these qualities may require more aggressive initial therapy.

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No description available.

Primary cell culture is limited by the increase in cellular levels of p16INK4a in response to an in vitro culture environment and, in conjunction with telomere shortening following cell division, presents a barrier to cellular proliferation. The use of transformed cell lines is limited for studies wherein the aim is to generate data akin to an in vivo environment as commonly such cell lines achieve their immortal benefits by down regulating important tumour suppressive mechanisms and inhibiting cell cycle checkpoints. Normal Human Oral Keratinocyte (NHOK) cells expressing shp16+hTERT were generated and compared to NHOK cells expressing Bmi1 +hTERT using an optimized retroviral transduction protocol and compared simultaneously to an epidermal control. Population doubling assessment of cell lines revealed that shp16+hTERT was not sufficient to extend replicative lifespan in the absence of p53 whilst cell lifespan extension was observed not only in cells expressing Bmi1+hTERT, but also in cells transduced with Bmi1 alone. Upon characterization, cells showed expression of p53 and responsiveness to UVB-induced apoptosis as demonstrated by an increase in p53 expression. NHOKBmi1+hTERT displayed adaptability to serum free culture when weaned into keratinocyte serum free media (KSFM) and retained the ability to stratify into multiple layers when supported by feeders on polycarbonate membrane inserts. The cell line NHOKBmi1+hTERT will be beneficial for in vitro studies looking to utilise an alternative to transformed or spontaneously derived cell lines and holds potential for further development and optimization into a well characterized SSE in a user friendly, and reproducible system for the testing for oral products.

Abstract PURPOSE: Hepatoma-derived growth factor (HDGF) is a unique nuclear/growth factor and plays an important role in the development and progression of cancer. The current study aimed to elucidate the correlation between HDGF expression, clinic-pathologic parameters, and associated molecular factors of oral cancer. MATERIALS AND METHODS: The surgically resected samples from a total of 95 patients with oral cancer (squamous cell carcinoma) were enrolled to construct the tissues microarray (TMA) in this retrospective study. The HDGF expression in TMA of oral cancer was determined by immunohistochemistry. HDGF and vascular endothelial growth factor (VEGF) immunostaining in tumor samples was scored and the labeling index were correlated with various clinic-pathologic parameters by statistic analysis. RESULTS: Expression of nuclear HDGF and VEGF was highly correlated with primary T stage (P=0.004 and P=0.038, respectively) and histological grade (P=0.013 and P=0.017, respectively). VEGF expression also associated with nodal status (P=0.021). Moreover, expression of nuclear HDGF and VEGF were highly correlated to each other (P=0.006). On the other hand, expression of HDGF in cytoplasm only associated with tumor necrosis (P=0.002) and showed no impact on survival. In univariate analysis, high expression of nuclear HDGF and VEGF significantly affected disease-specific, metastasis-free, and local recurrence-free survival. Multivariate analysis also indicated that expression level of nuclear HDGF is an independent prognostic factor for disease-specific and local recurrence-free survival (P=0.028; P=0.0285). Indeed, high expression of VEGF is also an independent factor in disease-specific, local recurrence-free, and metastasis free survival (P=0.0183; P=0.0461; P=0.0153). CONCLUSION: The data showed that high expression of nuclear HDGF and VEGF in squamous cell carcinoma of oral cavity might identify patients at risk of aggressive disease and predict poor prognosis. HDGF might play as key of regulation of tumorigenesis. Therefore, HDGF could be a candidate gene for the development of diagnostic and therapeutic strategies for oral cancer. Further studies are still need to determine the precise role of HDGF in the biological behavior of oral caner and the regulatory mechanism with other associated molecular factors.

The effect of natural compound AN30 on oral cancer cell line (Ca9-22), and normal oral cell line (HGF-1) was investigated. AN30 was purified from native fern plant Thelypteris torresiana. It had been reported to induce cell cycle arrest, apoptosis and DNA damage, cell growth inhibition in lung cancer cells, breast cancer cells and prostate cancer cells, but the effect in oral cancer is unknown. In a preliminary test, AN30 shows high toxicity to oral cancer cells but not normal oral cells. After treatment of AN30 to oral cancer cells, caspase activation and comet assays were performed to verity apoptosis induction. 2-D electrophoresis was used to find out the differentially expressed proteins between normal and cancer oral cell line under AN30 treatment. The proteins were further identified by LC/MS and western blot. The mechanism of these candidate proteins on drug toxicity remains further investigation.

One of the physiological functions of apoptosis is to eliminate cells that have sustained genetic aberrations, thereby preventing damaged cell from attaining uncontrolled cell proliferation or transformation into carcinoma. The apoptotic response is mediated by many apoptotic genes including Fas, survivin, caspases etc. through either the extrinsic pathway (death receptor pathway) or the intrinsic pathway (mitochondrial pathway). In this dissertation, we carried out a hospital-based case-control study to investigate the association between seven Fas related apoptosis pathway genes (Fas, FasL, survivin, XIAP, caspase-3, caspase-8 and caspase-9) and the risk for oral squamous cell carcinoma (OSCC). In this study, 279 newly diagnosed OSCC patients and 469 frequency-matched controls were recruited at Kaohsiung Veterans General Hospital from 2003 to 2006. Total eight various polymorphisms in seven genes mentioned above were examined by PCR-RFLP and our results showed that only FasL ¡V844TT genotype (P=0.047) was associated with the risk of OSCC. However, a trend of increased risk of OSCC was found in people with the increasing putative high-risk genotypes of Fas related apoptosis pathway genes (P for linear trend, 0.034). From our results of the gene-environment interaction analyses, three important observations were listed below: (1) the polymorphism of both FasL T-844C and survivin codon Lys129Glu were risk factors for Fukienese (P=0.023 and P=0.014, respectively), but not for other ethnicities examined. (2) For non-smokers, survivin codon Lys129Glu and caspase-3 A21926C polymorphisms had significant protect (P=0.047 and P=0.024, respectively). (3) For betel quid (BQ) chewers, caspase-9 codon Arg221Gln polymorphism was an important risk factor (P=0.048). Together, the results suggested that gene polymorphisms of Fas related apoptosis pathway were associated with the risk of OSCC. In order to evaluate the relationship between p53 and caspase-3 protein expression levels or clinicopathologic characteristics and survival outcome in OSCC, we examined the protein expression profilings of caspase-3 and p53 in those patients with buccal mucosa squamous cell carcinoma (BMSCC). Total 117 primary buccal carcinoma specimens were collected at KSVGH between 1990 and 2005 and their paraffin-embedded tissues were sectioned and subjected for immunohistochemistry examination. The overall cumulative survival rate was 62% for 5-years, 39% for 10-years and 18% for 14-years, respectively. Ours results showed that the survival rate of BMSCC was significantly correlated with all clinicopathological characteristics including cell differentiation, pathological stage, tumor size, lymph node metastasis, post-operative RT, post-operative CT and BQ chewing status. Most importantly, the high caspase-3 protein level in cytoplasm was an unfavorable prognostic factor in the univariate or the multivariate analysis. In conclusion, the join effect of genetic polymorphisms of Fas related apoptosis pathway genes and gene-environment combined effect may play important roles in the OSCC risk. In addition, high caspase-3 protein expression in cytoplasm may be used as a prognostic marker for patients with BMSCC.

Magister Scientiae Dentium - MSc(Dent) / Background: Reports on the global incidence of oral neoplasms indicate reduced data from Africa. Population based studies of oral cancer in Sudan and other regions of Africa are scarce. Oral cancer in Sudan constitutes a serious health problem, and squamous cell carcinoma (SCC) is the most prevalent type of oral malignancy. There are descriptive epidemiologic studies from Sudan that have reported high a frequency rate of oral cancer in Sudanese males, linking this high incidence to Toombak, a product of oral snuff mixed with sodium bicarbonate (Idris et al, 1995(b)), but to date no population-based studies of oral cancer incidence in Sudan have been performed or published. Title: Epidemiology of Oral Malignancy in Sudan (2004-2008). Aims and Objectives: The objectives of the study were to analyse the pattern of distribution and to determine the minimum age standardized incidence rates (ASIR) and the cumulative (lifetime) risk (CR) of oral & lip squamous cell carcinoma / oral malignancy by site, age and gender for the 5-year period 2004-2008. Methods: The records of patients with oral & maxillofacial and salivary malignancies (OMFS) referred to Khartoum Dental Teaching Hospital (KDTH) and the population census data were accessioned. Data was captured using Microsoft Excel 2007® and the ASIRs for oral squamous cell carcinoma (OSCC) were calculated using the direct International Agency for Research on Cancer (IARC) method. These results were compared with the on-line global cancer statistics database (GLOBOCAN -WHO/IARC) for 2008 and 2012. Records of oral cancer cases during the period of the study were obtained from KDTH. The information included in the raw data collected were the file number for patient identification, year of diagnosis, age, sex, site of the lesion, histological diagnosis, the International Classification of Diseases-10 (ICD10) codes, the referring unit and the state from which the patient was referred. The population data for the years of the study and the five age group stratifications was obtained from the Central Statistical Office in Khartoum, Sudan. The data was analysed using Microsoft Excel, 2007®. Age standardized incidence rate of oral & lip squamous cell carcinoma/ oral malignancy was calculated using the direct IARC method. Results: Of the total Sudanese population of 36.3 million in 2006, 649 OMFS malignancies (M:F=1.44:1) were captured at KDTH during the 5-year period; 390 (M:F=1.67:1) were (intra) oral squamous cancers (OSCC) and verrucous carcinomas (VC). The ASIR for OSCC/VC in Sudan was calculated as 3.19 for males and 1.83 for females (M:F=1.74:1), however the pooled ASIR in the Khartoum and Gezira States was 30% higher for males (4.21) and 14% higher for females (2.09, M:F=2.01:1).The incidence over the 5 years of separately recorded lip SCC/VC in Sudanese males was 26 and 8 for females (M:F=3.25:1).The ASIRs of combined oral & lip SCC/VC in Sudanese males was 3.45 and 1.88 for females (M:F=1.84:1). These compare relatively well with the GLOBOCAN data which estimates a slightly lower ASIR of 3.3 for males and somewhat higher ASIR of 2.1 for females (M:F=1.57:1). The cumulative (lifetime) risk (CR 0-74) of developing oral and lip cancer was 1: 182 for males compared to 1: 831 for females. For oral cancer (excluding lip), the CR was almost similar for males (1: 181); while females showed a markedly higher CR (1: 344). Conclusion: The combined ASIRs of oral & lip SCC/VC from the Khartoum and Gezira states differed from the ASIRs calculated for the entire Sudan and from the GLOBOCAN estimates. The recording of cancer incidence data can vary according to the (incorrect) labelling of anatomical locations and diagnosis. The numbers are influenced by geo-political, environmental and socio-economic factors, and referral bias.