Preoperative Serum Selenium Concentrations and Disease-Specific Survival in Patients With Oral Cancer: A Long-Term Follow-Up Study.

BACKGROUND: Serum selenium (Se) concentration has been reported to be associated with the incidence of oral cancer. The association between serum Se and long-term survival in oral cancer patients is still unclear. PURPOSE: The purpose of this study is to measure the association between serum Se and disease-specific survival (DSS). STUDY DESIGN, SETTING, AND SAMPLE: This was a single-center, prospective cohort study conducted at the First Affiliated Hospital of Fujian Medical University (Fujian Province, China) from September 2011 to December 2018. The inclusion criteria were patients with newly diagnosed primary oral cancer confirmed by histology. The exclusion criteria were patients with recurrent oral cancer or metastatic cancer. PREDICTOR VARIABLE: The predictor variable is the preoperative serum Se concentration measured using inductively coupled plasma-mass spectrometry. MAIN OUTCOME VARIABLE(S): The primary outcome variable is DSS calculated from the date of diagnosis to the date of death due to oral cancer or the end of follow-up, whichever occurred first. COVARIATES: The covariates were age, sex, occupation, education level, body mass index, surgery therapy, adjuvant therapy, tumor node metastasis stage, and pathological grading. ANALYSES: Kaplan-Meier survival analysis, Cox proportional hazards regression, and restricted cubic spline regression were utilized. P value < .05 was significant. RESULTS: The sample was composed of 235 subjects with a median age of 59 years (ranged from 20 to 80 years) and 142 (60.43%) were male. The median follow-up was 54.90 months (interquartile range: 35.47). Se levels were associated with DSS (unadjusted hazard ratio [HR] = 0.70; 95% confidence interval [CI]: 0.54-0.91) suggesting that higher levels of Se are associated with longer or improved DSS. After adjustment of age, sex, occupation, education level, residence, tumor node metastasis stage, pathological grading, surgery therapy, radiotherapy, and chemotherapy, patients with higher serum Se had a better DSS (aHR = 0.67; 95% CI: 0.49-0.92). Of note, we found that the association between serum Se and DSS was observed only in patients with radiotherapy (aHR = 0.49; 95% CI: 0.33-0.73). And the protective effect of radiotherapy on survival was only observed in patients with higher Se concentrations (aHR = 0.36; 95% CI: 0.20-0.63). Additionally, there was a multiplicative interaction between Se and radiotherapy on the prognosis of oral cancer patients (Pinteraction<0.01). CONCLUSION AND RELEVANCE: Our findings suggest that a high Se concentration might contribute to better DSS among oral cancer patients, and the effect may partly depend on radiotherapy treatment. Given these findings, additional research should focus on the role of Se in DSS among oral cancer patients and the interaction with radiotherapy.

Erythrocyte ω-3 polyunsaturated fatty acids are inversely associated with the risk of oral cancer: a case-control study.

OBJECTIVES: Evidence about ω-3 polyunsaturated fatty acids (ω-3 PUFAs) and oral cancer risk were limited. We aimed to evaluate the association of erythrocyte ω-3 PUFAs with the risk of oral cancer in a population from China. METHODS: Erythrocyte ω-3 PUFAs of 236 oral cancer patients and 300 controls were determined by gas chromatography. Restricted cubic spline and logistic regression were used to analyze the association between erythrocyte ω-3 PUFAs and oral cancer risk. The crude and adjusted OR with 95% CI was calculated. Stratification analysis was performed to explore the potential interaction between ω-3 PUFAs and other traditional risk factors such as smoking and drinking. RESULTS: Eicosapentaenoic acids (EPA), docosahexaenoic acids (DHA) and ω-3 index were negatively but non-linearly related to risk of oral cancer as observed by restricted cubic spline. The adjusted OR of EPA, DHA, and ω-3 index were 0.52 (95% CI: 0.35-0.76), 0.19 (95% CI: 0.08-0.44), 0.20 (95% CI: 0.09-0.44), respectively. Stratification analysis showed that the adverse correlation between EPA and oral cancer was only significant in the non-smoking group, while the adverse correlation of ɑ-linolenic acid (ALA), EPA, and DHA were only significant in the non-drinking group. General multiplicative interactions were observed between ω-3 PUFAs and smoking or drinking. CONCLUSIONS: Adverse but non-linear associations were observed between erythrocyte EPA, DHA, ω-3 index, and oral cancer risk. Additionally, there were multiplicative interactions between ω-3 PUFAs and other behavior factors such as smoking and drinking. The protective effect of ω-3 PUFAs maybe more significant in the non-smoking or non-drinking population.

An insight into crystallization test: A neoteric approach for screening premalignant and malignant lesions.

INTRODUCTION: Crystallization test is based on the principle that, when a salt crystallizes out of an aqueous solution, the crystal growth is influenced by the presence of other substances in the solution, such as blood or plant extracts. If a mixture of copper chloride solution with a small amount of whole blood is allowed to crystallize under controlled experimental conditions, an aggregate of crystals forms. Crystallization method can be used as a diagnostic aid to provide information about the systemic conditions and general health of the patient. AIM: This study aims to study the patterns of crystallization and to further determine the efficacy of crystallization test as a screening modality in premalignant lesions and oral squamous cell carcinoma (OSCC). MATERIALS AND METHODS: Fifty patients of OSCC, 50 patients of premalignant lesions, and 50 healthy individuals were selected. One drop of blood was collected from the study groups to perform crystallization using cupric chloride. STATISTICAL ANALYSIS USED: Statistical analysis was performed using Chi-square test, Student's t-test (two-tailed), and analysis of variance. RESULTS: The different patterns of crystals formed were studied and statistically analyzed. CONCLUSION: Based on the study, it was concluded that Crystallization test can be used as an effective screening modality for detection of premalignant lesions and OSCC.

The risks of ubiquinone and ß-carotene deficiency and metabolic disorders in patients with oral cancer.

BACKGROUND: Cancer development is mediated by oxidative stress and inflammation, which may correlate with metabolic disorders. The aim of this study was to evaluate antioxidant vitamins status and metabolic parameters in patients with oral cancer according to tumor-node-metastasis (TNM) stages. METHODS: A total of 194 patients with oral cancer were enrolled in this study. The patients were stratified for four groups according to cancer stages and that the statistics are comparisons across these groups. The levels of antioxidant vitamins (ubiquinone, ß-carotene, vitamin A and E), metabolic parameters, oxidative stress, antioxidant enzymes activity, and inflammatory markers were measured. RESULTS: More than half of the subjects had high blood pressure, central obesity, hyperglycemia, and hyperlipidemia regardless of TNM stage. With regard to antioxidant vitamins status, 46 and 94% of patients had ß-carotene and ubiquinone deficiency, respectively. Patients in T3 and T4 stages had significantly lower antioxidant enzyme (catalase, p = 0.03) activity and higher inflammatory markers levels (high sensitivity C-reactive protein and interleukin-6, p < 0.01) than patients in the other stages. In addition, the level of ß-carotene was negatively associated with waist circumference, and ubiquinone was positively associated with the level of high-density lipoprotein cholesterol (p < 0.05). Higher ß-carotene and ubiquinone levels were negatively associated with hypertriglyceridemia and the risk of metabolic syndrome (p < 0.05). CONCLUSIONS: A high proportion of patients with oral cancer had ubiquinone or ß-carotene deficiency and metabolic disorders. The level of ubiquinone or ß-carotene was negatively associated with the risk of central obesity, hypertriglyceridemia, and metabolic syndrome. Since patients with oral cancer suffer from high oxidative stress and inflammation (particularly in the T3 and T4 stages), supplementation with antioxidant vitamins such as ubiquinone or ß-carotene could be preferentially applied.

Serum levels of 25-hydroxy-vitamin D in patients with oral squamous cell carcinoma: Making a case for chemoprevention.

OBJECTIVES: Serum level of vitamin D has been used as a predictor for cancer development. We intend to measure the baseline vitamin D level in patients with oral squamous cell carcinoma (OSCC) and to compare same with non-cancer controls to determine any association. MATERIALS AND METHODS: Patients with OSCC presenting to our clinics were included in this study. Their baseline serum vitamin D levels were measured prior to cancer treatment after obtaining their consents. These patients were then matched with at least 2 cancer-free subjects to serve as controls and whose serum vitamin D levels were also measured. The serum vitamin D levels obtained for the two groups were then categorized into normal (>35 ng/ml), mild deficiency (25-35 ng/ml), moderate deficiency (12.5-25 ng/ml), and severe deficiency (<12.5 ng/ml). The data were analyzed statistically and the two groups compared. RESULTS: A total of 51 patients with OSCC (Male 22 [43%] and female 29 [57%]) and 113 cancer-free controls (Male 36 [31.86%] and female 77 [68.14%]) were included in the study. The commonest site for OSCC was the tongue, accounting for 45% of the cancer cases. Mean age for cancer patients was 59.33 years ±12.54 and 49.24 years ±15.79 for the control. Among the OSCC patients, 74.51% had moderate to severe vitamin D deficiencies, whereas only 20.35% had a moderate deficiency in the control group with no severe deficiency. CONCLUSION: Logistic regression analysis shows a positive association between vitamin D deficiency and OSCC risk especially in levels below 25 ng/ml. This further corroborates the assertion that vitamin D deficiency may be a useful indicator of OSCC. It may, therefore, be necessary to routinely prescribe vitamin D supplements to subjects with moderate to severe deficiencies in order to decrease the chances of OSCC development.

Impact of dietary vitamin D on initiation and progression of oral cancer.

Calcitriol, the active metabolite of vitamin D, has been widely studied for its preventive and therapeutic activity against several cancers including oral squamous cell carcinoma (OSCC). However, the impact of dietary vitamin D supplementation on initiation and progression of OSCC is unclear. To address this gap in knowledge, we conducted preclinical trials using the 4-nitroquinoline-1-oxide 4NQO carcinogen model of oral carcinogenesis. Female C57BL/6 mice were maintained on one of three vitamin D diets [25 IU, 100 IU, 10,000 IU] and exposed to 4NQO in drinking water for 16 weeks followed by regular water for 10 weeks. Body weight measurements obtained through the study duration did not reveal any differences between the three diets. Animals on 100 IU diet showed lower incidence of high-grade dysplasia/OSCC and higher CD3 + T cells compared to animals on 25 IU and 10,000 IU diets. Serum 25OHD3 levels were highest in animals on 10,000 IU diet at week 0 prior to carcinogen exposure but showed ∼50 % reduction at week 26. Histologic evaluation revealed highest incidence of OSCC in animals maintained on 10,000 IU diet. Animals on 100 IU and 10,000 IU diets showed higher vitamin D receptor VDR and CYP24A1 immunostaining in high-grade dysplastic lesions and OSCC compared to normal tongue. Validation studies performed in a 4NQO-derived OSCC model showed that short-term treatment of animals on a 25 IU diet with calcitriol significantly inhibited tumor growth compared to controls but did not affect tumor growth in animals on reference diet 1000 IU. Collectively, our results highlight the complex dynamics between vitamin D status and oral carcinogenesis. Our observations also suggest that therapeutic benefits of short-term calcitriol treatment may be more pronounced in vitamin D deficient hosts.

[Relationship between selenium and the risk for oral cancer: a case-control study].

Objective: To explore the relationship between selenium and the risk for oral cancer. Methods: We performed a case-control study in 325 cases of newly diagnosed primary oral cancer from the First Affiliated Hospital of Fujian Medical University and 650 controls from the same hospital and community. Unconditional logistic regression and stratification analyses were used to explore the association between selenium and oral cancer. Adjusted OR and corresponding 95%CI were calculated. The analyses on multiple interactions between selenium and smoking or drinking status, and fruit or fish intake frequencies were conducted. Results: The level of serum selenium was 112.42 (80.98-145.06) µg/L in the case group, which was lower than 164.85 (144.44-188.53) µg/L in control group, the difference was statistical significant (P<0.01). There was a negative correlation between serum selenium level and the risk for oral cancer regardless of smoking and drinking status, and fruits and fish intake frequencies (P<0.05). There were multiple interactions between serum selenium level and smoking or drinking status, and fruit and fish intakes. Conclusions: The high level of serum selenium is a protective factor for the incidence of oral cancer, and serum selenium has multiple interactions with smoking or drinking status, and fruit and fish intakes. Therefore, reducing tobacco use and alcohol consumption and increasing the intakes of fruit and fish can reduce the risk for oral cancer to some extent.

Dosimetry study on radioactive particle brachytherapy in oral carcinoma.

PURPOSE: To investigate the therapeutic effects of different doses of 125I radioactive particle brachytherapy on oral cancer. METHODS: Between September 2012 and September 2015, 78 patients with oral cancer who received 125I radioactive particle brachytherapy for the first time in our hospital were enrolled in this study. Patients were divided into high dose (≥3) and low dose (<3) groups. The treatment outcome, serum tumor marker levels and the expression levels of autophagy and apoptotic genes in tumor cells were compared between groups. RESULTS: Complete remission (CR)+partial remission (PR) ratio in the high dose group was significantly higher than that of the low dose group. Stable disease (SD)+ progressive disease (PD) ratio was significantly lower in the high dose group. The serum levels of TSGF, SCCA, CEA, CA125, CA15.3, CA19.9 and PSA oral cancer markers were significantly lower than those of the low dose group. In the high dose group, the expression levels of Beclin-1 and MAP1LC3 (autophagic genes) mRNAs were significantly higher than those of the low dose group, while the expression levels of EMMPRIN and MMP-14 (invasive genes) mRNAs were significantly lower in the high dose group. Also survival rates in the responsive patients were significantly better in comparison to non-responsive patients. CONCLUSION: High dose particle brachytherapy with radioactive 125I is a safe and effective treatment and its clinical results were more beneficial than the low dose therapy.

p120-Catenin Is Required for Dietary Calcium Suppression of Oral Carcinogenesis in Mice.

Previous studies have shown that dietary calcium suppresses oral carcinogenesis, but the mechanism is unclear. p120-catenin (p120) is a cytoplasmic protein closely associated with E-cadherin to form the E-cadherin-ß-catenin complex and may function as a tumor suppressor in the oral epithelium. To determine whether p120 is involved in the mechanism by which dietary calcium suppresses oral carcinogenesis, The normal, low, or high calcium diet was fed control mice (designated as floxed p120 mice) or mice in which p120 was specifically deleted in the oral squamous epithelium during the adult stage (designated as p120cKO mice). All mice were exposed to a low dose of oral cancer carcinogen 4-nitroquinoline 1-oxide and rates of oral squamous cell carcinoma (OSCC) and proliferation and differentiation in the cancerous and non-cancerous oral epithelium of these mice were examined. The results showed that the low calcium diet increased rates of OSCC and proliferation of the non-cancerous oral epithelium and decreased differentiation of the non-cancerous oral epithelium, but had no effect on cancerous oral epithelium. In contrast, the high calcium diet had opposite effects. However, the effect of the dietary calcium on the rates of OSCC, proliferation, and differentiation of the non-cancerous epithelium were not seen in p120cKO mice. Based on these results, we conclude that p120 is required for dietary calcium suppression of oral carcinogenesis and oral epithelial proliferation and dietary calcium induction of oral epithelial differentiation. J. Cell. Physiol. 232: 1360-1367, 2017. © 2016 Wiley Periodicals, Inc.

Cupreous Complex-Loaded Chitosan Nanoparticles for Photothermal Therapy and Chemotherapy of Oral Epithelial Carcinoma.

Electron transition materials on the basis of transition metal ions usually possess higher photothermal transduction efficiency but lower extinction ability, which have not been considered as efficient photothermal agents for therapeutic applications. In this work, we demonstrate a facile and feasible approach for enhancing 808 nm photothermal conversion effect of d orbits transition Cu(II) ions by forming Cu-carboxylate complexes. The coordination with carboxylate groups greatly enlarges the splitting energy gap of Cu(II) and the capability of electron transition, thus enhancing the extinction ability in near-infrared region. The cupreous complexes are further loaded in biocompatible and biodegradable polymer nanoparticles (NPs) of chitosan to temporarily lower the toxicity, which allows the photothermal therapy of human oral epithelial carcinoma (KB) cells in vitro and KB tumors in vivo. Animal experiments indicate the photothermal tumor inhibition rate of 100%. In addition, the gradual degradation of chitosan NPs leads to the release of cupreous complexes, thus exhibiting additional chemotherapeutic behavior in KB tumor treatment. Onefold chemotherapy experiments indicate the tumor inhibition rate of 93.1%. The combination of photothermal therapy and chemotherapy of cupreous complex-loaded chitosan NPs indicates the possibility of inhibiting tumor recurrence.

Berberine prevents 7,12-dimethylbenz[a]anthracene-induced hamster buccal pouch carcinogenesis: a biochemical approach.

Chemoprevention, a novel and useful approach in experimental oncology, deals with the prevention, suppression, or inhibition of carcinogenesis using natural or synthetic entities. This study evaluated the chemopreventive potential of berberine on 7,12-dimethylbenz[a]anthracene (DMBA)-induced hamster buccal pouch carcinogenesis. Oral squamous cell carcinoma was developed in the buccal pouch of golden Syrian hamsters by painting with 0.5% DMBA in liquid paraffin three times a week for 14 weeks. Tumor incidence, tumor volume, tumor burden, phase I and phase II carcinogen detoxification agents, lipid peroxidation, antioxidant status, and histopathological changes were assessed in hamsters treated with DMBA alone and in DMBA+berberine-treated animals. Hundred percent tumor incidences with an imbalance in carcinogen-metabolizing enzymes and cellular redox status were observed in hamsters treated with DMBA alone. Oral administration of berberine at a dose of 75 mg/kg body weight (bw) to DMBA-treated hamsters completely prevented tumor incidence and restored the status of the above-mentioned biochemical markers. Berberine, a traditional drug from Southeast Asia, shows promising chemopreventive efficacy in hamster buccal pouch carcinogenesis.

Effect of mangrove black tea extract from Ceriops decandra (Griff.) on hematology and biochemical changes in dimethyl benz[a]anthracene-induced hamster buccal pouch carcinogenesis.

Effect of the black tea extracted from a mangrove plant species, Ceriops decandra (Griff.) was studied on dimethyl benz[a]anthracene (DMBA)-induced changes in blood hematology and plasma non-enzymatic antioxidants in male hamsters. Hamsters were painted with 0.5% solution of DMBA in liquid paraffin on the right buccal pouch three times in a week up to 14 weeks. Each application treated with 0.4mg of DMBA. The mangrove black tea extract (MBTE) was administrated orally with 5mgkg(-1) twice a day and then with DMBA on alternate days. Results showed that the DMBA caused a significant (P<0.05) decline in the levels of reduced glutathione (GSH), vitamin-C, -E, red blood cells, hemoglobin, mean corpuscular volume and hematocrit; and increase in the levels of WBC, platelets, lymphocytes and neutrophils. The MBTE prevented the DMBA-induced adverse changes significantly in blood and biochemical parameters of the male hamsters. This work concluded that the black tea extracted from the coastal mangrove species C. decandra prevented the DMBA-induced buccal pouch carcinogenesis in hamsters.

Possible action mechanism for curcumin in pre-cancerous lesions based on serum and salivary markers of oxidative stress.

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.

Protective effect of Withaferin-A on tumour formation in 7,12-dimethylbenz[a]anthracene induced oral carcinogenesis in hamsters.

With an aim to investigate the protective effect of Withaferin-A on 7,12-dimethylbenz[a]anthracene (DMBA) induced oral carcinogenesis in Syrian golden hamsters, tumour incidence, tumour volume and tumour burden and status of detoxication agents, lipid peroxidation and antioxidants in DMBA administered (3 times/week for 14 weeks) hamsters were assessed. Hundred percent tumour formation in DMBA alone administered animal was observed. Oral administration of Withaferin-A (20 mg/kg body weight) to DMBA administered animals for 14 weeks completely prevented the tumour incidence, tumour volume and tumour burden. Also, Withaferin-A showed significant anti-lipid peroxidative and antioxidant properties and maintained the status of phase-I and phase-II detoxication agents during DMBA-induced oral carcinogenesis. The results thus indicate that the protective effect of Withaferin-A is probably due to its anti-lipid peroxidative and antioxidant functions as well as modulating effect on carcinogen detoxication during DMBA-induced oral carcinogenesis.

Immunological and biochemical markers in oral carcinogenesis: the public health perspective.

Oral health is an integral component of general health and well being and a basic human right. Dental public health is probably the most challenging specialty of dentistry. Because of the lack of adequate resources among other factors, many people are likely to suffer from dental diseases. Despite great improvements in the oral health status of populations across the world, the burden and impact of dental diseases are still high. This is particularly true among underprivileged groups in both developed and developing communities. Oral diseases and conditions, including oral cancer, oral manifestations of HIV/AIDS, dental trauma, craniofacial anomalies, and noma, all have broad impacts on health and well-being. Oral cancer, the sixth most common cancer worldwide continues to be most prevalent cancer related to the consumption of tobacco, alcohol and other carcinogenic products. Nevertheless, significant reduction in mortality can be achieved by advances in early diagnosis and implementation of multidisciplinary treatment programs leading to improvement of survivorship and better quality of life. The present study was designed to evaluate the immunologic and biochemical markers in oral carcinogenesis using circulating immune complexes (CIC), copper, iron, and selenium concentrations as assessment endpoints. Study results indicated an increase in CIC and copper levels, and a decrease in iron and selenium concentrations in oral cancer patients compared to controls. The implications of these findings for public health are discussed.

Lipid peroxidation, total antioxidant status, and total thiol levels predict overall survival in patients with oral squamous cell carcinoma.

Tobacco is the major etiological factor for oral cancer development through the generation of oxidative stress. Therefore, markers of oxidative stress such as total antioxidant status, lipid peroxidation, and total thiol levels might be useful to monitor oxidative stress and predict overall survival in oral cancer patients. The study included 140 oral cancer patients and 50 healthy controls, who were classified as with the habit of tobacco and no habit of tobacco. Adjacent normal and malignant tissue samples were collected from oral cancer patients. Plasma and tissue levels of lipid peroxidation, thiol, and total antioxidant status were assayed by spectrophotometric methods. Thiol levels were significantly lower in controls with the habit of tobacco (P= .033), oral cancer patients (P= .0001), and malignant tissues (P= .015) as compared to controls with no habit of tobacco, controls with the habit of tobacco, and adjacent normal tissues, respectively. Tobacco exposure was higher in oral cancer patients than controls with the habit of tobacco. Controls with the habit of tobacco who had lower thiol (odds ratio [OR]=10.58, P= .008) and high tobacco exposure (OR=0.251, P= .05) showed an elevated risk of oral cancer development. Patients showing a lipid peroxidation level above the cutoff level as compared to patients below the cutoff level showed poor overall survival, whereas those with thiol and total antioxidant status levels below the cutoff level as compared to their respective counterparts showed poor overall survival. In conclusion, lipid peroxidation and thiol could be useful for predicting the risk of oral carcinogenesis in healthy tobacco consumers and predicting overall survival of oral cancer patients.

Oxidative stress in lymphocytes, neutrophils, and serum of oral cavity cancer patients: modulatory array of L-glutamine.

OBJECTIVES: Our aim was to assess the oxidative stress and ameliorative effect of L-glutamine in serum, neutrophils, and lymphocytes of oral cancer patients by measuring the levels of malondialdehyde (MDA) and antioxidants. MATERIALS AND METHODS: This study has been conducted on serum and specific blood cells in adult, male oral cancer patients (stage III-6, stage IV-42) and normal subjects of an equal number of age and sex-matched disease-free healthy subjects. The levels of lipid peroxidation and antioxidant enzymes were assayed using spectrophotometric methods. RESULTS: MDA levels were elevated, and antioxidant enzyme status was decreased significantly in all groups of cancer patients simultaneously, but after supplementation of "glutammune" (66.66% L-glutamine), oxidative stress has been alleviated to some extent; especially, it has repaired the glutathione cascade system. CONCLUSION: We conclude that oxidative stress is due to the enhanced lipid peroxidation and decrease in antioxidant enzymes, and it can be restored with dietary supplementation of L-glutamine related drug.

Circulating immune complexes and trace elements (Copper, Iron and Selenium) as markers in oral precancer and cancer : a randomised, controlled clinical trial.

AIM: To evaluate the levels of circulating immune complexes, trace elements (copper, iron and selenium) in serum of patients with oral submucous fibrosis (OSMF), oral leukoplakia (L), and oral squamous cell carcinoma (SCC), analyze the alteration and identify the best predictors amongst these parameters for disease occurrence and progression. METHODS: Circulating immune complexes (CIC) were estimated using 37.5% Polyethylene Glycol 6000(PEG) serum precipitation. Serum estimation of copper (Cu), Iron (Fe) and selenium (Se) was done using the Oxalyl Dihydrazide method, Colorimetric Dipyridyl method and the Differential Pulse Cathodic Stripping Voltametry respectively. RESULTS: The data analysis revealed increased circulating immune complex levels in the precancer and cancer patients. Serum copper levels showed gradual increase from precancer to cancer patients. However, serum iron levels were decreased significantly in the cancer group. Selenium levels showed marked decrease in the cancer group. Among CIC, serum, copper, iron and selenium the best predictors for the occurrence of lesions were age, serum iron, CIC, serum selenium in the decreasing order. CONCLUSION: The present study shows that these immunological and biological markers may be associated with the pathogenesis of oral premalignant and malignant lesions and their progressions. Concerted efforts would, therefore, help in early detection, management, and monitoring the efficacy of treatment.

Enhancement of erythrocyte antioxidants by green and black tea polyphenols during 7,12-dimethylbenz[a]anthracene-induced hamster buccal pouch carcinogenesis.

We evaluated the comparative chemopreventive efficacy of green tea polyphenols (polyphenon-E) and black tea polyphenols (polyphenon-B) on 7,12-dimethylbenz[a]anthracene (DMBA)-induced hamster buccal pouch (HBP) carcinogenesis. Lipid peroxidation, reduced and oxidized glutathione (GSH and GSSG, respectively), and the GSH-dependent enzymes glutathione peroxidase and glutathione S-transferase in the erythrocytes were used as biomarkers of chemoprevention. Enhanced lipid peroxidation in erythrocytes of DMBA-treated animals was accompanied by a significant decrease in the antioxidant status. Dietary administration of polyphenon-E and -B to DMBA-treated animals significantly decreased the extent of lipid peroxidation and enhanced the levels of GSH, GSH/GSSG ratio, and activities of GSH-dependent enzymes. Our study provides evidence that polyphenon-B is more effective in inhibiting HBP carcinogenesis than polyphenon-E by enhancing the antioxidant status, suggesting that polyphenon-B may have a major impact in the chemoprevention of oral cancer.

Levamisole and/or Chinese medicinal herbs can modulate the serum level of squamous cell carcinoma associated antigen in patients with erosive oral lichen planus.

The serum levels of squamous cell carcinoma associated antigen (SCCA) were determined by a microparticle enzyme immunoassay in a group of patients with stage I oral squamous cell carcinoma (OSCC), major or minor type erosive oral lichen planus (EOLP), recurrent aphthous stomatitis (RAS), Behçet's disease (BD), oral leukoplakia (OL), or oral submucous fibrosis (OSF), and in normal control subjects. About 97% of the normal control subjects and the patients with minor type EOLP, RAS, BD, OL or OSF had a serum level of SCCA within the normal limit of 1.2 ng/ml. However, 6 of the 12 (50%) patients with stage I OSCC and 14 of the 31 (45.2%) patients with major type EOLP had a serum level of SCCA greater than 1.2 ng/ml. The mean serum level of SCCA in stage I OSCC patients (1.38+/-1.16 ng/ml) or in major type EOLP patients (1.32+/-1.23 ng/ml) was significantly higher than that in normal control subjects (P<0.001) and that in the patients with minor type EOLP (P<0.001), RAS (P<0.001), BD (P<0.05), OL (P<0.05), or OSF (P<0.05). Either major or minor type EOLP patients could obtain a significant mean reduction of the serum SCCA level of 0.34-0.63 ng/ml after treatment with levamisole and/or Chinese medicinal herbs for 1-30 months. Combination therapy with levamisole plus Chinese medicinal herbs could achieve a shorter duration of treatment to get complete remission than the single therapy with either levamisole only or Chinese medicinal herbs only. We conclude that levamisole and/or Chinese medicinal herbs can modulate the serum SCCA level in EOLP patients. SCCA may be a useful marker in evaluating therapeutic effects and in monitoring the disease status of EOLP. For EOLP patients, the combination therapy is superior to the single therapy of levamisole or of Chinese medicinal herbs.