ascorbic-acid and Leukoplakia--Oral

We performed a randomized controlled chemoprevention trial of oral leukoplakia by administrating a low dose of beta-carotene and vitamin C supplements. 17% of subjects in the experimental arm (4/23) demonstrated clinical remission (complete or partial response) at completion of the trial. The objective of this study was to determine whether baseline expression of p53 and ki67 demonstrated any differences between those responding or not responding to our intervention. A secondary objective was to elucidate any relationship between dietary factors and clinical responses.. For this biomarker study, we included all subjects in the experimental group (n = 23) who were non-smokers. Among 16 who completed the trial for 1 year of supplementation, there were four responders and 12 non-responders at 1-year follow-up. Following immuno-staining for p53 and ki67, the percentage of positive cell nuclei were analyzed as labeling index (LI).. Expression of p53 was greater in basal layers than in para-basal layers. Mean para-basal LI of p53 was higher in non-responding (26.0) than in responding subjects (11.2) (P = 0.028). ki67 LIs were not significantly different in the two groups.. Expression of p53 was inversely related to clinical response to the supplements. Other biomarkers that may recognize subject's responsiveness to chemoprevention require further study.

Topics: Aged; Ascorbic Acid; beta Carotene; Biomarkers; Dietary Supplements; Female; Humans; Ki-67 Antigen; Leukoplakia, Oral; Male; Treatment Outcome; Tumor Suppressor Protein p53

Management of oral leukoplakia-a potentially malignant disorder-is currently not evidence-based. Of the few randomized trials that have been reported, most have negative data. Therefore, a multi-centre, randomized, double-blind controlled trial (RCT) was undertaken to evaluate the use of low-dose beta-carotene combined with vitamin C supplements for the treatment and to prevent malignant transformation of oral leukoplakia. 46 Japanese participants with oral leukoplakia were allocated randomly either to an experimental arm (10 mg day(-1) of beta-carotene and 500 mg day(-1) of vitamin C) or placebo arm (50 mg day(-1) of vitamin C). Current or ex-smokers within 3 months of cessation were excluded. The supplements were continued over a period of 1 year. The primary endpoint was clinical remission at 1-year and the likelihood of malignant transformation during a 5-year follow-up period as a secondary endpoint. The overall clinical response rate in the experimental arm was 17.4% (4/23) and 4.3% (1/23) in the placebo arm (p = 0.346). During the median 60-month follow-up period, two subjects in the experimental arm and three in the control arm developed oral cancer. Under the intention-to-treat principle, relative risk by supplementing with beta-carotene and vitamin C was 0.77 (95%CI: 0.28-1.89) (p = 0.580) by the Cox proportional hazards model. No unfavorable side-effects were noted. Beta-carotene (10 mg day(-1) ) and vitamin C were neither effective for clinical remission, nor for protection against the development of cancer. Data from this RCT does not support the hypothesis that chemoprevention with this treatment is effective for oral leukoplakia.

Topics: Adult; Aged; Ascorbic Acid; beta Carotene; Cell Transformation, Neoplastic; Dietary Supplements; Disease Progression; Female; Follow-Up Studies; Humans; Leukoplakia, Oral; Male; Middle Aged; Risk Factors; Treatment Outcome

Seventy-nine patients with oral leukoplakia that was histologically verified as either hyperkeratosis or epithelial dysplasia with hyperkeratosis were enrolled in an antioxidant supplementation program for the treatment of the oral lesions. The patients received 30 mg of beta-carotene, 1000 mg of ascorbic acid, and 800 IU of alpha-tocopherol per day for 9 months. Clinical improvement of the oral lesion was noted in 55.7% of the patients and was more likely to occur in patients who reduced their use of alcohol or tobacco (p = 0.0056). Although risk-factor reduction was important, approximately half of the patients who did not alter their exposure to either alcohol or tobacco showed clinical improvement. The antioxidant supplementation significantly increased serum and tissue levels of beta-carotene, ascorbic acid, and alpha-tocopherol, but these changes did not correlate strongly with clinical improvement.

Topics: Adult; Aged; Aged, 80 and over; Alcohol Drinking; Antioxidants; Ascorbic Acid; beta Carotene; Carotenoids; Female; Humans; Leukoplakia, Oral; Male; Middle Aged; Risk Factors; Smoking; Treatment Outcome; Vitamin E

The objectives of this study are to analyze oxidative DNA and lipid damage using salivary 8-hydroxy-2-deoxyguanosine (8-OHdG), malondialdehyde (MDA), and vitamins C and E in oral lichen planus lesions, oral leukoplakia, oral submucous fibrosis, oral squamous cell carcinoma (SCC), and controls and to determine the value of salivary biomarkers in the diagnosis of oral pre-cancer and cancer patients.. Unstimulated saliva was collected from a group of patients diagnosed with 40 oral squamous cell carcinoma (OSCC), 40 oral lichen planus lesions, 40 oral leukoplakia, 40 oral submucous fibrosis, and from a control group of healthy age- and gender-matched individuals. Salivary 8-OHdG, MDA, and vitamins C and E were measured.. Squamous cell carcinoma and pre-cancer patients showed significantly higher levels of salivary 8-OHdG and MDA and lower levels of vitamins C and E when compared to levels in healthy normal subjects. The specificity and sensitivity of the combination of 8-OHdG, MDA, vitamin C, and vitamin E are high for the diagnosis of oral pre-cancer and SCC compared to an individual biomarker approach using either 8-OHdG, MDA, or vitamin C and vitamin E independently.. This study indicates the presence of oxidative DNA and lipid damage in pre-cancerous and SCC patients. It is postulated that the mechanism may have a significant link to carcinogenesis in oral cancer. Detection of salivary 8-OHdG, MDA, vitamin C, and vitamin E can act as suitable diagnostic biomarkers of oral pre-cancer and cancer.. Of clinical importance is that salivary 8-OHdG, MDA, vitamin C, and vitamin E could play a significant role in oral cancer and pre-cancer patients and could therefore be useful for diagnosis in patients with oral lichen planus lesions, oral leukoplakia, oral submucous fibrosis, and oral squamous cell carcinoma.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adult; Ascorbic Acid; Biomarkers; Biopsy; Carcinoma, Squamous Cell; Case-Control Studies; Deoxyguanosine; Female; Free Radicals; Humans; Leukoplakia, Oral; Lichen Planus, Oral; Male; Malondialdehyde; Middle Aged; Mouth Neoplasms; Oral Submucous Fibrosis; Precancerous Conditions; Risk Factors; Saliva; Sensitivity and Specificity; Vitamin E

Extensive research within the past half-century has indicated that curcumin (diferuloylmethane), a yellow pigment in curry powder, exhibits anti-oxidant, anti-inflammatory, and pro-apoptotic activities. We investigated whether the anti-pre-cancer activities assigned to curcumin are mediated through an anti-oxidant and DNA-protecting mechanism. Patients with oral leukoplakia, oral submucous fibrosis or lichen planus, and healthy individuals (n = 25 for each group) aged 17-50 years were selected. Salivary and serum oxidative markers such as malonaldehyde (MDA), 8-hydroxydeoxyguanosine (8-OHdG), vitamins C and E were measured just prior to the intake of curcumin, after one week of curcumin intake and following clinical cure of precancerous lesions. Serum and salivary vitamins C and E showed increases, while MDA and 8-OHdG levels showed decreases in patients with oral leukoplakia, submucous fibrosis and lichen planus after intake of curcumin for all categories of precancerous lesions. The changes in these values were observed to be statistically significant after clinical cure of the disease (P < 0.05). The five-point rating scale for pain, as well as lesion size in oral leukoplakia, submucous fibrosis and lichen planus, improved significantly (P < 0.05). In addition, in submucous fibrosis, mouth opening (P < 0.05) recovered significantly. In oral leukoplakia, submucous fibrosis and lichen planus, the levels of serum and salivary vitamins C and E increased significantly, while MDA and 8-OHdG levels decreased after 131(15), 211(17), and 191(18) days, respectively. Values for serum and salivary vitamins C and E showed a significant decrease in oral leukoplakia, submucous fibrosis and lichen planus, in contrast to healthy individuals, but increased significantly in all groups subsequent to curcumin administration after clinical cure of lesions. Based on these results, we can conclude that curcumin mediates its anti-pre-cancer activities by increasing levels of vitamins C and E, and preventing lipid peroxidation and DNA damage.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adolescent; Adult; Antioxidants; Ascorbic Acid; Biomarkers; Curcumin; Deoxyguanosine; DNA; DNA Damage; Female; Follow-Up Studies; Free Radical Scavengers; Humans; Leukoplakia, Oral; Lichen Planus, Oral; Lipid Peroxidation; Male; Malondialdehyde; Middle Aged; Mouth Neoplasms; Oral Submucous Fibrosis; Oxidative Stress; Pain Measurement; Precancerous Conditions; Protective Agents; Saliva; Vitamin E; Young Adult

To evaluate the role of vitamins C and E as chemopreventive agents in oral carcinogenesis by optical and ultrastructural studies.. The cheek pouch of male hamsters was treated with the oral carcinogen, dimethylbenz(a)anthracene (DMBA), to induce multiple tumour formation. Vitamins C and E were applied either singly or in combination as a chemopreventive agent. Paraffin and resin-embedded sections of the hamster cheek pouch were studied optically and ultrastructurally.. The epithelium of control hamsters showed hyperorthokeratosis and parakeratosis, but did not develop well differentiated squamous cell carcinoma (WDSCC). Ninety percent of the animals treated with DMBA alone showed WDSCC while 10% of the animals developed papillomas. There was also a marked increase in the number of cells undergoing mitosis in this group. A reduction in the yield (1.1 tumour/animal) and rate 60-80% of squamous cell carcinomas but not of papillomas (2.0 papillomas/animal) was observed in groups VI-VIII treated with DMBA and vitamins C and E singly or in combination as compared to those of DMBA only. In animals treated with DMBA plus vitamins C and E, statistical significant decrease in the number of animals with tumours and mitotic basal cells was observed when compared with the DMBA treated group. Control animals showed normal ultrastructural morphology while tumour-bearing animals showed basal lamina in a discontinuous, fragmented, broken and diffused basement membrane, with diminished lamina densa, fewer hemidesmosomes and invagination of the basal cell cytoplasmic processes in the subepithelium.. These results indicate that vitamin E singly or in combination with vitamin C plays a role in the inhibition of tumour cell growth.

Topics: 9,10-Dimethyl-1,2-benzanthracene; Animals; Anticarcinogenic Agents; Antioxidants; Ascorbic Acid; Basement Membrane; Carcinogens; Carcinoma, Squamous Cell; Cheek; Chemoprevention; Chi-Square Distribution; Cricetinae; Cytoplasm; Drug Combinations; Epithelium; Hemidesmosomes; Leukoplakia, Oral; Male; Mesocricetus; Mitosis; Mouth Mucosa; Mouth Neoplasms; Papilloma; Parakeratosis; Vitamin E

To investigate the relationship of specific nutrients and food items with oral precancerous lesions among tobacco users.. A population-based case-control study.. Villages in Palitana taluk of Bhavnagar district, Gujarat, India.. An interviewer-administered food frequency questionnaire, developed and validated for this population, was used to estimate nutrient intake in blinded, house-to-house interviews. Among 5018 male tobacco users, 318 were diagnosed as cases. An equal number of controls matched on age (+/- 5 years), sex, village, and use of tobacco were selected.. Odds ratios (OR) from multiple logistic regression analysis controlling for relevant variables (type of tobacco use and economic status).. A protective effect of fibre was observed for both oral submucous fibrosis (OSF) and leukoplakia, with 10% reduction in risk per g day-1 (P < 0.05). Ascorbic acid appeared to be protective against leukoplakia with the halving of risk in the two highest quartiles of intake (versus the lowest quartile: OR = 0.46 and 0.44, respectively; P < 0.10). A protective effect of tomato consumption was observed in leukoplakia and a suggestion of a protective effect of wheat in OSF.. In addition to tobacco use, intake of specific nutrients may have a role in the development of oral precancerous lesions.

Topics: Adult; Ascorbic Acid; Case-Control Studies; Diet; Diet Surveys; Dietary Fiber; Feeding Behavior; Humans; India; Leukoplakia, Oral; Logistic Models; Male; Micronutrients; Middle Aged; Multivariate Analysis; Odds Ratio; Oral Submucous Fibrosis; Plants, Toxic; Precancerous Conditions; Smoking; Solanum lycopersicum; Surveys and Questionnaires; Tobacco, Smokeless; Triticum

Vitamins, such as A, beta carotene, C, E, B12 and folate, are the micronutrients with the strongest evidence of having a link to cancer prevention and control. Deficiency of these vitamins at the dietary, systemic or mucosal level will interact with tobacco use and increase the risk of oral precancerous lesions. The objective of this study was to (1) establish the baseline circulating levels of these vitamins in our normal population with and without tobacco use and (2) compare these levels with the values obtained in cases of oral leucoplakias. 50 normal controls with 25 each in chewers and non-chewers, matched for age and sex, were selected. 50 cases of oral leucoplakias (clinically detectable white patches) from the field constituted the study group. Simultaneous measurement of serum vitamin B12 and folate were carried out by radioassay. The other serum vitamins were estimated spectrophotometrically. Except for serum vitamin E, all the other serum vitamin levels were significantly decreased in oral leucoplakias compared to the controls. Cancer chemopreventive agents acting as inhibitors of both initiation and promotion, as analysed in our population, is promising for further intervention trials.

Topics: Ascorbic Acid; beta Carotene; Carotenoids; Case-Control Studies; Folic Acid; Humans; Leukoplakia, Oral; Plants, Toxic; Tobacco, Smokeless; Vitamin A; Vitamin B 12; Vitamin E; Vitamins

Forty young adult male Syrian hamsters (Mesocricetus auratus) were divided into four groups of 10 animals. The animals in group 1 (tumor control) had the right buccal pouches painted three times a week with a 0.5% solution of 7,12 dimethylbenz(a)anthracene in heavy mineral oil USP with the use of a number 4 sable brush. The animals in group 2 (experimental group) had the right buccal pouches painted with the same solution as group 1. In addition, they received 1 mg ascorbic acid in 0.5 ml mineral oil three times a week on days alternating with the other application. The ascorbic acid was administered by mouth with the use of a pipette. The animals in group 3 received 1 mg ascorbic acid in 0.5 ml mineral oil three times weekly, and the animals in group 4 were untreated controls. The animals were killed after 14 weeks. Tumors were counted and measured. Both right and left (control) pouches were photographed, excised, fixed in formalin, sectioned in paraffin, and studied histologically. The animals that received the ascorbic acid (vitamin C) had significantly larger tumors in the right buccal pouch, although actual numbers of gross tumors were only slightly increased. The figures for tumor burden in the animals in groups 1 and 2 were 364 versus 648 mm3. Histologic study revealed that the animals in group 2 had more anaplastic tumors and a significantly greater number of areas of dysplastic leukoplakia than the animals in group 1.

Topics: 9,10-Dimethyl-1,2-benzanthracene; Animals; Ascorbic Acid; Carcinogens; Carcinoma, Squamous Cell; Cheek; Cocarcinogenesis; Cricetinae; Drug Synergism; Leukoplakia, Oral; Male; Mesocricetus; Mouth Neoplasms

The role of vitamin C in maintaining mucosal health is poorly documented. The purpose of this study was to examine the presence of oral mucosal lesions in subjects with low ascorbic acid (AA) levels in plasma. AA plasma levels of 843 working elderly people in six rural villages in Eastern Finland were determined. All subjects with low plasma AA levels (< or = 25 mumol/l) (n = 106) formed the study group. Controls with normal AA levels (> or = 50 mumol/l) (n = 103) were drawn from the same population. They were matched for age, sex and number of teeth. Oral mucosal lesions in all subjects were recorded clinically using a double-blind method in all subjects. Petechias, leukoplakia and lichenoid lesions were the commonest lesions of the oral mucosa. Only in leukoplakia there was a statistically significant difference between the groups (p < 0.01). Smokers had more leukoplakia than non-smokers. The prevalence of leukoplakia was higher when smoking was combined with AA deficiency.

Topics: Adult; Ascorbic Acid; Ascorbic Acid Deficiency; Double-Blind Method; Female; Humans; Leukoplakia, Oral; Lichenoid Eruptions; Male; Middle Aged; Mouth Diseases; Mouth Mucosa; Prevalence; Purpura; Smoking; Surveys and Questionnaires

Vitamin C is an essential nutrient whose protective influence in carcinogenesis has been reported frequently. In general, evidence suggests that vitamin C inhibits the formation of some carcinogens and decreases the incidence and delays the onset of neoplastic lesions but the mechanisms by which this occurs are not known. In 1973, Wallenius and Lekholm induced intra-oral palatal squamous cell carcinomas by the use of the water soluble carcinogen 4-nitroquinoline-1-oxide (4NQO) applied thrice weekly to the palatal mucosa of rats. The aim of this study was to determine if in rats topically applied vitamin C had an effect on the process of carcinogenesis caused by the application of 4NQO. The results of this study showed that in the 4NQO treated animals a progression through mild, moderate and severe dysplasia occurred prior to neoplastic changes at 24 weeks and that this progression was delayed in the animals treated topically with vitamin C. It can be concluded that topically applied vitamin C has a modulating effect on the neoplastic process induced by 4NQO in the palatal mucosa of rats.

Topics: 4-Nitroquinoline-1-oxide; Administration, Topical; Animals; Ascorbic Acid; Carcinoma, Squamous Cell; Epithelium; Hyperplasia; Leukoplakia, Oral; Male; Mouth Mucosa; Mouth Neoplasms; Palate; Rats; Rats, Inbred Strains; Time Factors

Topics: Adult; Aged; Antioxidants; Ascorbic Acid; Combined Modality Therapy; Cryosurgery; Drug Combinations; Female; Humans; Hydrolases; Leukocytes; Leukoplakia, Oral; Male; Middle Aged; Vitamin A; Vitamin E

Topics: Ascorbic Acid; Chymotrypsin; Female; Humans; Hydrocortisone; Iontophoresis; Leukoplakia, Oral; Male

Male Syrian golden hamsters receiving 12 weekly subcutaneous injections of diethylnitrosamine (DEN) were subjected to cigarette smoke-inhalation and fed a diet or without 1% vitamin C supplement for a period of 58 weeks. Another group was a sham-smoked control and was not fed vitamin C. Tissues of the oral cavity and costal cartilage were examined by light and/or scanning electron microscopy. Oral leukoplakia and costochondral hyperplasia occurred with high frequency in all groups treated with DEN. Leukoplakic lesions were found in the palate, tongue, and pharynx; the early change was focal erosion with mild epithelial hyperplasia and inflammatory cell infiltration. Advanced lesions had marked mucosal thickening due to acanthosis, parakeratosis, hyperkeratosis, and submucosal infiltration of lymphocytes and plasma cells. Precancerous lesions were noted in tongue and pharynx. Scanning electron microscopy of tongues revealed destruction of filiform papillae. The incidence of leukoplakic lesions were higher in smoke-exposed hamsters than in controls, but the incidence in vitamin C-supplemented hamsters was low when compared with the smoke-exposed hamsters without vitamin C. Costochondral hyperplasia was initiated by thickening of the perichondrium followed by proliferation of chondrocytes. Costochondral hyperplasia appeared earlier, and the incidence was higher in the vitamin C-supplemented hamsters. It could not be determined whether costochondral hyperplasia was the primary lesion induced by DEN or secondary change.

Topics: Animals; Ascorbic Acid; Cartilage; Cartilage Diseases; Cricetinae; Diethylnitrosamine; Hyperplasia; Leukoplakia, Oral; Male; Mesocricetus; Microscopy, Electron, Scanning; Palate; Pharynx; Ribs; Smoking; Tongue

Topics: Ascorbic Acid; Blood Chemical Analysis; Calcium; Carotenoids; Drug Therapy; Humans; Leukoplakia; Leukoplakia, Oral; Liver; Mouth Diseases; Pathology; Phosphorus; Strontium; Thyroid Hormones; Tongue Diseases; Toxicology; Vitamin A