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Biomedical subjects

S Warnakulasuriya

Publications and source records attributed to S Warnakulasuriya.

At least 19 recordsLinked to original sources
PubMed2001

Serum antioxidant micronutrient levels in oral lichen planus.

The aim of this study was to elucidate any association between oral lichen planus (OLP) and serum antioxidant micronutrients by a population-based case-control study. A total of 9536 subjects were examined, and 62 (58 reticular, 4 atrophic and erosive) diagnosed with OLP at referral facilities were compared with four controls per case (n=248) selected among disease-free subjects matched for age and sex. Serum levels of micronutrients (retinol, alpha-tocopherol, zeaxanthin/lutein and cryptoxanthin, lycopene, alpha-carotene and beta-carotene) were estimated by the high performance liquid chromatography (HPLC) method. Among cases, mean serum retinol level (2.820+/-0.849 micromol/l) was significantly higher compared with that of controls (2.562+/-0.735 micromol/l) (P<0.05). No significant differences were noted in carotenoid levels examined in this study, except for a lower level of lycopene found in atrophic/erosive OLP cases. The results of this study suggest that low serum retinol or carotenoid levels are not risk factors for occurrence of lichen planus, and any specific benefits of antioxidant micronutrients cannot be claimed for this inflammatory disorder.

Adult↗
PubMed2000

Lack of molecular markers to predict malignant potential of oral precancer.

Studies on the natural history of oral squamous cell carcinoma suggest a clinically detectable phase which precedes the development of cancer. Among the precancerous states, leukoplakia is the most commonly encountered clinical lesion. Although epithelial dysplasia is the most important predictive factor, non-dysplastic lesions in the oral cavity may transform with time. Early reports describing p53 overexpression in oral leukoplakia has resulted in many authors misinterpreting this result by concluding that p53 is an early marker of oncogenesis. Using sequential biopsies, few reports have critically examined the clinical significance of p53 as a risk marker. These studies suggest that p53 protein stabilization, or indeed the spectrum of mutations of p53, has no major relationship to the biological characteristics and outcome of oral leukoplakia. When used as a single marker, p53 is unsuitable for the prediction of tumour development in high-risk subjects and no other maker has yet emerged as useful. Despite the impact of molecular diagnostics on the diagnosis of tumours, assessing a patient's risk for development of cancer of the oral cavity remains limited to 'H&E' pathology.

Biomarkers, Tumor↗
PubMed2000

p53 and P-glycoprotein expression are significant prognostic markers in advanced head and neck cancer treated with chemo/radiotherapy.

The development of biological markers of response to chemo- and radiotherapy to judge benefit to risk ratios for toxic treatments is still at an experimental stage. Tumour cell death is largely by apoptosis and the p53 gene has a major influence on this. P-glycoprotein (P-gp) accumulation has been correlated with treatment failure in several types of cancer. p53 and P-gp expression were studied in 111 advanced head and neck cancers treated with radiotherapy and up to four courses of synchronous or sequential chemotherapy. The probability of survival at 5 years for patients in the trial as a whole was 27.7%, while the cohort used for this marker project was 29.4%. Among the subjects used for the marker study at the time of analysis, 13 remained disease-free and 18 were alive. Immunohistochemistry was used to assess p53 and P-gp expression; 27/111 (24%) head and neck cancers demonstrated p53/P-gp expression and 33/111 (30%) were both p53- and P-gp- negative. In univariate analysis, both p53 and P-gp expression were associated with reduced disease-free and overall survival. Multivariate analysis revealed tumour size, p53, and P-gp expression as the most powerful pretreatment prognosticators in the study cohort. Long-term follow-up results suggest that p53 and P-gp co-expression predicts the biological behaviour or the outcome following chemo/radiotherapy in advanced head and neck cancer.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2000

Expression of p53 in oral squamous cell carcinoma is associated with the presence of IgG and IgA p53 autoantibodies in sera and saliva of the patients.

Around 50% of head and neck cancers are known to have aberrations of the p53 gene. Overexpression of the mutant p53 protein can induce a specific humoral response in cancer patients. Matched saliva, serum, and tissue samples from 26 patients with histologically confirmed oral squamous and verrucous carcinoma were investigated. p53 protein expression was evaluated by immunohistochemistry and antibodies specific for 53 protein were analysed in sera and whole mouth saliva by ELISA, immunoprecipitation, and competition assays; 16/25 (64%) samples demonstrated the stabilized p53 protein in tissues and 7/26 (27%) had a high level of p53 antibody in serum. In samples where matching saliva was available, p53 antibody was also present in saliva. In some tumours, only IgA-type p53 antibody was detected. p53 antibodies were found only in the serum and saliva of patients who showed p53 overexpression in their tumour tissues. These results demonstrate that detection of p53 antibodies can offer a specific and non-invasive method for the detection of a subset of tumours with p53 aberrations.

Autoantibodies↗
PubMed2000

Outcome following a population screening programme for oral cancer and precancer in Japan.

The purpose of this study was to evaluate the validity and outcome of an oral mucosal screening programme conducted in Japan. All adults over the age of 40 years resident in Tokoname city were invited by letter to attend a free general health screen and oral examinations annually. Twenty- to 39-year-old females were also encouraged to participate. During the years 1996-98, a total of 19056 subjects (5885 male, 13171 female: mean age 60.7+/-11.3 years) were examined by three types of screeners: postgraduate dental residents (n=17), hospital dentists (n=5) and general dental practitioners (n=15). In the cohorts examined screening dentists recorded oral mucosal lesions in 783 (4.1%) subjects. Of those detected with mucosal lesions, 200 (25.5%) were referred and 137 (68. 5%) attended for follow up examination in hospital departments by specialists with full diagnostic back up facilities. Thirty-nine subjects were confirmed as having oral cancer or precancer (two squamous cell carcinomas, 37 leukoplakias) and 40 with lichen planus. Five false positives (3.6%) were found. Among the cases referred under other diagnostic labels no cancers were detected. Among those who attended for confirmation of oral cancer or precancer by a specialist, sensitivity, specificity and positive predictive value were 0.92, 0.64 and 0.78, respectively. In males with oral cancer/leukoplakia, the prevalence of smoking, drinking and combined habits was higher than those with lichen planus or among negative subjects. The sensitivity and specificity determined from this research suggests that the performance of the Japanese dentists employed in screening was satisfactory. An attendance of 68% for re-examination by specialists compares well with other reported studies measuring patient compliance.

Adult↗
PubMed2000

Serum antioxidant micronutrients and the risk of oral leukoplakia among Japanese.

A population-based case-control study was designed for the investigation of any association between serum micronutrient levels and oral leukoplakia. Out of a total of 9536 subjects over the age of 40 years who participated in the oral mucosal screening programme in Tokoname city, 48 cases detected with oral leukoplakia (38 male:10 female) were recruited. For each case, four controls matched by age and sex were selected from the same cohort. We examined the fasting serum levels of retinol, alpha-tocopherol, zeaxanthin and lutein, cryptoxanthin, lycopene and carotenoids (alpha-carotene and beta-carotene) by high-performance liquid chromatography. Among males with leukoplakia mean serum lycopene and beta-carotene levels (0.175+/-0.202, 0.357+/-0.295 micromol/l) were significantly lower than those of controls (0.257+/-0.252, 0.555+/-0.408 micromol/l) (P<0.05, P<0.005). Logistic regression analysis with leukoplakia as the dependent variable showed that high serum levels of beta-carotene were related to low risk of oral leukoplakia (odds ratio 0.160, 95% C.I.: 0.029-0.866, P<0.05). There were no significant differences in any of the serum nutrients estimated in female subjects. Our results suggest for the first time that high serum levels of beta-carotene may provide protection against oral precancer for the Japanese male.

Adult↗
PubMed2000

Oral cancer screening as an integral part of general health screening in Tokoname City, Japan.

OBJECTIVES: To measure the attendance and compliance rates in oral mucosal screening (OMS) offered as part of a general health screen (GHS) undertaken as an organised programme in Japan. METHODS: In 1996, all adults over the age of 40 years resident in Tokoname City were invited by letter to attend a free GHS annually, conducted by the municipal cooperation and the medical and dental societies of Tokoname City. In the later years only those who attended in 1996 were reinvited. Females aged less than 39 years were also allowed to attend if they wished to participate in the GHS. The GHS consisted of completion of a self administered questionnaire to identify past and current illnesses and any medications used by the screened population coupled with a routine physical check, chest x ray, ECG, and blood and urine examination. The GHS was programmed annually during the years 1996 to 1998. All those attending the GHS were invited to participate in an OMS conducted under the same roof by a visiting dentist (n=37). A referral pathway was established for screen positives requiring follow up. RESULTS: A total of 19 305 subjects (5955 males, 13350 females; mean age 59.2 years; 7033 in 1996, 6289 in 1997, and 5983 in 1998) attended the GHS. Of those who attended the GHS, 19 056 (98.7%) attended the OMS (1.3% refused). This rate was fairly constant over the three years. Excluding repeat examinations, new cases recruited for OMS over the three years were 8723. Of those participating in OMS, 4269 (60.7%) attended all three years. In the cohorts examined, screening dentists recorded oral mucosal lesions in 5.4% in 1996, in 4.0% in 1997, and in 2.6% in 1998. Overall, this amounted to a positive detection rate of 4.1%, or 4.9% excluding repeat examinations. A higher prevalence of oral pre-cancer was recorded among male smokers. CONCLUSIONS: The overall results suggest that although compliance with attending a free GHS was low (26.2%) among Japanese subjects over 40 years of age, of those who complied 74-76% reattended annually. Hence a satisfactory participation rate can be obtained in Japan for OMS when this is coupled to a GHS conducted at the same visit.

Adult↗
PubMed1999

Role of p16/MTS1, cyclin D1 and RB in primary oral cancer and oral cancer cell lines.

One of the most important components of G1 checkpoint is the retinoblastoma protein (pRB110). The activity of pRB is regulated by its phosphorylation, which is mediated by genes such as cyclin D1 and p16/MTS1. All three genes have been shown to be commonly altered in human malignancies. We have screened a panel of 26 oral squamous cell carcinomas (OSCC), nine premalignant and three normal oral tissue samples as well as eight established OSCC cell lines for mutations in the p16/MTS1 gene. The expression of p16/MTS1, cyclin D1 and pRB110 was also studied in the same panel. We have found p16/MTS1 gene alterations in 5/26 (19%) primary tumours and 6/8 (75%) cell lines. Two primary tumours and five OSCC cell lines had p16/MTS1 point mutations and another three primary and one OSCC cell line contained partial gene deletions. Six of seven p16/MTS1 point mutations resulted in termination codons and the remaining mutation caused a frameshift. Western blot analysis showed absence of p16/MTS1 expression in 18/26 (69%) OSCC, 7/9 (78%) premalignant lesions and 8/8 cell lines. One cell line, H314, contained a frameshift mutation possibly resulting in a truncated p16/MTS1 protein. pRB was detected in 14/25 (56%) of OSCC but only 11/14 (78%) of these contained all or some hypophosphorylated (active) pRB. In premalignant samples, 6/8 (75%) displayed pRB, and all three normal samples and eight cell lines analysed contained RB protein. p16/MTS1 protein was undetectable in 10/11 (91%) OSCCs with positive pRB. Overexpression of cyclin D1 was observed in 9/22 (41%) OSCC, 3/9 (33%) premalignant and 8/8 (100%) of OSCC cell lines. Our data suggest p16/MTS1 mutations and loss of expression to be very common in oral cancer cell lines and less frequent in primary OSCC tumours. A different pattern of p16/MTS1 mutations was observed in OSCC compared to other cancers with all the detected p16/MTS1 mutations resulting in premature termination codons or a frameshift. The RB protein was expressed in about half (44%) of OSCCs and its expression inversely correlated with p16/MTS1 expression. In conclusion, we show that abnormalities of the RB pathway are a common mechanism of oral carcinogenesis.

Carcinoma, Squamous Cell↗
PubMed1999

Oral mucosal lesions associated with betel quid, areca nut and tobacco chewing habits: consensus from a workshop held in Kuala Lumpur, Malaysia, November 25-27, 1996.

A variety of betel/areca nut/tobacco habits have been reviewed and categorized because of their possible causal association with oral cancer and various oral precancerous lesions and conditions, and on account of their widespread occurrence in different parts of the world. At a recent workshop in Kuala Lumpur it was recommended that "quid" be defined as "a substance, or mixture of substances, placed in the mouth or chewed and remaining in contact with the mucosa, usually containing one or both of the two basic ingredients, tobacco and/or areca nut, in raw or any manufactured or processed form." Clear delineations on contents of the quid (areca nut quid, tobacco quid, and tobacco and areca nut quid) are recommended as absolute criteria with finer subdivisions to be added if necessary. The betel quid refers to any quid wrapped in betel leaf and is therefore a specific variety of quid. The workshop proposed that quid-related lesions should be categorized conceptually into two categories: first, those that are diffusely outlined and second, those localized at the site where a quid is regularly placed. Additional or expanded criteria and guidelines were proposed to define, describe or identify lesions such as chewer's mucosa, areca nut chewer's lesion, oral submucous fibrosis and other quid-related lesions. A new clinical entity, betel-quid lichenoid lesion, was also proposed to describe an oral lichen planus-like lesion associated with the betel quid habit.

Areca↗
PubMed1998

p53 alterations and HPV infections are common in oral SCC: p53 gene mutations correlate with the absence of HPV 16-E6 DNA.

To examine the association between HPV infections and p53 gene aberrations, a panel of 28 oral squamous cell carcinomas (SCC) and 12 potentially malignant oral mucosal lesions were analysed for p53 mutations in exons 2-9. p53 protein was analysed by immunocytochemistry using DO7 antibody. The same panel was also examined for the possible presence of HPV infection. p53 overexpression was detected in 13/26 (50%) malignant and 2/9 (22%) premalignant lesions. Mutations in the coding region of the p53 gene were found in 10 malignant samples. None of the premalignant lesions were shown to have p53 mutations. The total number of p53 mutations in 10 samples were 14 of which 12 (85%) were in exon 5 suggesting the presence of hot spots in exon 5 for carcinogens involved in the transformation of oral epithelial cells. The presence of HPV DNA was first screened with consensus primers to the L1 region and nested PCR approach. HPV 6 and HPV 16 were detected in 14/28 (50%) oral SCC and 4 of 12 (33%) precancerous lesions, 7 tumours harboured both types. The samples were then examined for the presence of E6 oncogenic sequence of HPV16 using E6 specific primers. 7/27 (26%) SCC and 5/9 (55%) premalignant lesions harboured E6 DNA of which 6 (3 SCC and 3 premalignant) were negative with L1 primers suggesting possible integration of the specific viral genes or loss of other viral DNA sequences after integration of larger viral fragments. 9/10 (90%) SCC with p53 mutations were negative for E6 DNA. Our results show that both p53 alterations and HPV infection may be important etiological factors in the development of oral cancer. However, there is: i) No concordance between p53 mutations and its overexpression. ii) the presence of HPV capsid DNA (L1) does not necessarily indicate the presence of HPV oncogenic genes. iii) p53 gene mutations, but not overexpression, correlate with the absence of HPV 16-E6 and not L1 gene.

Aged↗
PubMed1997

Evaluation of multiple micronutrient supplementation in the management of oral submucous fibrosis in Karachi, Pakistan.

Oral submucous fibrosis (OSF) is an oral precancerous condition characterized by symptoms such as intolerance to spicy food, altered salivation, progressive difficulty in opening the mouth, and signs like vesiculation, ulceration, blanching, rigidity, and stiffening of the oral mucosa and depapillation and altered mobility of the tongue. It is seen mostly among people of Indian subcontinent origin. The major structural change is extensive fibroelastic scarring of the lamina propria and deeper connective tissues. A combination of micronutrients (vitamins A, B complex, C, D, and E) and minerals (iron, calcium, copper, zinc, magnesium, and others) was evaluated for its efficacy in controlling the symptoms and signs of OSF in 117 compliant subjects in Karachi, Pakistan, in a single-arm preliminary study. The subjects received supplementation for one to three years. Significant improvement in symptoms, notably intolerance to spicy food, burning sensation, and mouth opening, was observed at exit. The interincisor distance deteriorated in 11 subjects (10%) at exit; it was stable in 56 subjects (49%) and improved in 48 (41%). The mean interincisor distance was 19.1 +/- 10.8 (SD) mm at exit compared with 16.2 +/- 7.5 mm at baseline. A significant proportion of concomitant lesions like leukoplakia also regressed at exit. The major outcome from this study was a beneficial clinical response in subjects with OSF to multiple micronutrient intervention, which justifies its further evaluation in well-designed randomized controlled trials in other settings in South Asia.

Adolescent↗
PubMed1997

Our third year.

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Europe↗