ascorbic-acid and Head-and-Neck-Neoplasms

Among individuals with a history of head and neck cancer and tobacco abuse the risk of second primary cancers in the upper aerodigestive tract is high. Chemoprevention of oral squamous cell carcinomas is based on two conditions: Premalignant mucosa lesions are treated with chemopreventive agents in order to prevent malignant conversion (primary prevention). In secondary prevention of oral cancer, after curative therapy patients are treated by chemoprevention in order to reduce the rate of second primaries. This paper presents a comprehensive clinical review of oral cancer prevention studies, highlighting the agents mostly used, such as beta-carotene, alpha-tocopherol, ascorbic acid, and retinoids. Although most intervention trials showed good overall response with these substances, high relapse rates and serious side effects, in most cases related to the retinoid compounds were noticed. In addition, in all prospective randomized chemoprevention trials (CARET, ATBC and PHS) no significant evidence of benefit for supplementation with alpha-tocopherol, beta-carotene or retinyl palmitate was reported.

Topics: Antineoplastic Agents; Ascorbic Acid; Carcinoma, Squamous Cell; Carotenoids; Chemoprevention; Head and Neck Neoplasms; Humans; Mouth Neoplasms; Neoplasms, Second Primary; Retinoids; Treatment Outcome; Vitamin E

Epidemiologic investigations have been instrumental in identifying numerous factors associated with the development of cancer. Tobacco and alcohol are unquestionably the major risk factors for squamous cell carcinoma of the head and neck region. Diet appears to play a role in the development of these cancers, as nutritional deficiencies have been found to increase risk. Clinical observation and epidemiologic studies have also identified ionizing radiation as an unequivocal risk factor, although of lesser importance from the public health point of view. Overall, epidemiologic evidence shows that occupational exposures play a minor, though definite, role in the development of head and neck cancer. For sinonasal cancer, however, studies corroborate that occupational exposures are the major determinants of disease.

Topics: Ascorbic Acid; Carcinoma, Squamous Cell; Ethanol; Fruit; Head and Neck Neoplasms; Humans; Neoplasms, Radiation-Induced; Occupational Diseases; Risk; Smoking; United States; Vegetables; Vitamin A

The present study was conducted to determine the preventive efficacy of vitamin C/E complex supplementation for radiotherapy (RT)-induced xerostomia in patients with head and neck cancer.. Prospective, double-blinded, randomized, placebo-controlled study.. A single tertiary referral institution.. The trial group (n = 25) received antioxidant supplements (100 IU of vitamin E + 500 mg of vitamin C) twice per day during RT, while the control group (n = 20) received an identical placebo. Pre-RT and 1 and 6 months post-RT, patient-reported xerostomia questionnaires, observer-rated xerostomia score, and salivary scintigraphy were serially obtained to compare xerostomia severity between the 2 groups.. The trial group showed greater improvements in xerostomia questionnaire and score at 6 months post-RT when compared with those at 1 month post-RT (P = .007 and .008, respectively). In contrast, the control group showed no changes between 1 and 6 months post-RT. By salivary scintigraphy, there was no difference in maximal accumulation or ejection fraction between the 2 groups. However, the trial group maintained significantly better oral indices at the prestimulatory (P = .01) and poststimulatory (P = .009) stages at 1 month post-RT, compared with the control group. At the final follow-up, there was no difference in overall survival and disease-free survival between the 2 groups.. Our data suggest that short-term supplementation with an antioxidant vitamin E/C complex exerts a protective effect against RT-induced xerostomia.

Topics: Ascorbic Acid; Double-Blind Method; Female; Head and Neck Neoplasms; Humans; Male; Middle Aged; Prospective Studies; Radiation Injuries; Surveys and Questionnaires; Treatment Outcome; Vitamin E; Xerostomia

Diet may modulate the risk of head and neck cancer (HNC) through antioxidant and anti-inflammatory effects. To date, there is limited evidence regarding the effects of the Mediterranean diet on HNC risk. The purpose of the study was to assess the association between Mediterranean diet adherence, type of diet, and vitamin C and the risk of HNC. A case-control study was conducted at the Dentistry Hospital, University of Barcelona, including 101 cases of HNC and 101 controls matched by age and sex. Dietary habits were assessed using a 14-question Mediterranean diet score that classified the type of diet into healthy diet (10-14 points), regular diet (5-9 points), and unhealthy diet (≤4 points). Multivariate logistic regression models were used to assess the association between Mediterranean diet adherence, type of diet, and vitamin C and the risk of HNC. Higher adherence to the Mediterranean diet was significantly associated with a lower risk of HNC (OR = 0.88, 95% CI: 0.79-0.98). A healthy diet (OR = 0.29, 95% CI: 0.10-0.84) and vitamin C intake (OR = 0.25, 95% CI: 0.10-0.62) were strongly associated with lower odds of HNC. Moderate egg intake was the only type of food significantly associated with a lower risk of HNC. Dietary patterns that emphasize a high intake of antioxidant and anti-inflammatory bioactive components may have a protective effect on the risk of HNC.

Topics: Antioxidants; Ascorbic Acid; Case-Control Studies; Diet, Mediterranean; Head and Neck Neoplasms; Humans; Risk Factors; Vitamins

Topics: Ascorbic Acid; Carcinoma, Squamous Cell; Cell Line, Tumor; Eating; Gene Expression Regulation, Neoplastic; Head and Neck Neoplasms; Humans; MicroRNAs; Squamous Cell Carcinoma of Head and Neck; Sugars; Vitamins

Over production of reactive oxygen species (ROS) caused by altered redox regulation of signaling pathways is common in many types of cancers. While PET imaging is recognized as the standard tool for cancer imaging, there are no clinically-approved PET radiotracers for ROS-imaging in cancer diagnosis and treatment. An ascorbate-based radio ligand promises to meet this urgent need. Our laboratory recently synthesized [

Topics: Animals; Ascorbic Acid; Doxorubicin; Head and Neck Neoplasms; Ligands; Liver Neoplasms; Male; Mice; Primates; Rats; Reactive Oxygen Species; Rodentia; Squamous Cell Carcinoma of Head and Neck; Tissue Distribution

Evidence of associations between single nutrients and head and neck cancer (HNC) is still more limited and less consistent than that for fruit and vegetables. However, clarification of the protective mechanisms of fruit and vegetables is important to our understanding of HNC etiology. We investigated the association between vitamin C intake from natural sources and cancer of the oral cavity/pharynx and larynx using individual-level pooled data from ten case-control studies (5,959 cases and 12,248 controls) participating in the International Head and Neck Cancer Epidemiology (INHANCE) consortium. After harmonization of study-specific exposure information via the residual method, adjusted odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were estimated using unconditional multiple logistic regression models on quintile categories of 'non-alcohol energy-adjusted' vitamin C intake. In the presence of heterogeneity of the estimated ORs among studies, we derived those estimates from generalized linear mixed models. Higher intakes of vitamin C were inversely related to oral and pharyngeal (OR = 0.54, 95% CI: 0.45-0.65, for the fifth quintile category versus the first one, p for trend<0.001) and laryngeal cancers (OR = 0.52, 95% CI: 0.40-0.68, p for trend = 0.006), although in the presence of heterogeneity among studies for both sites. Inverse associations were consistently observed for the anatomical subsites of oral and pharyngeal cancer, and across strata of age, sex, education, body mass index, tobacco, and alcohol, for both cancer sites. The inverse association of vitamin C intake from foods with HNC may reflect a protective effect on these cancers; however, we cannot rule out other explanations.

Topics: Ascorbic Acid; Case-Control Studies; Head and Neck Neoplasms; Humans; International Agencies; Italy; Japan; Logistic Models; Risk Factors; Surveys and Questionnaires; Switzerland; United States; Vitamins

Head and neck cancer (HNC) is the seventh most-common type of cancer worldwide. Evidence regarding the potential protective effect of vitamins and carotenoids on HNC is limited and mostly based on case-control studies.. We evaluated the association of intake of dietary vitamins C and E (including supplementation) and the most-common carotenoids (α-carotene, β-carotene, lutein plus zeaxanthin, lycopene, and β-cryptoxanthin) and risk of HNC and HNC subtypes in a large prospective study.. The Netherlands Cohort Study included 120,852 participants. For efficiency reasons, a case-cohort design was used. At baseline in 1986, participants completed a food-frequency questionnaire. A subcohort was randomly selected from the total cohort. After 20.3 y of follow-up, 3898 subcohort members and 415 HNC cases [131 oral cavity cancer (OCCs), 88 oro-/hypopharyngeal cancer (OHPs), and 193 laryngeal cancer cases] were available for analysis. Rate ratios and 95% CIs for highest (quartile 4) compared with lowest (quartile 1) quartiles of vitamin and carotenoid intake were estimated by using the Cox proportional hazards model.. A strong inverse association was shown between vitamin C and HNC overall (multivariable-adjusted rate ratio for quartile 4 compared with quartile 1: 0.39; 95% CI: 0.23, 0.66; P-trend < 0.001), OCC (multivariable-adjusted rate ratio for quartile 4 compared with quartile 1: 0.35; 95% CI: 0.16, 0.77; P-trend < 0.05), and OHPC (multivariable-adjusted rate ratio for quartile 4 compared with quartile 1: 0.29; 95% CI: 0.12, 0.67; P-trend < 0.01). No statistically significant results were shown for vitamin E, α-carotene, β-carotene, lycopene, and lutein plus zeaxanthin. The association of vitamin E and HNC was modified by alcohol status (P-interaction = 0.003) with lower risks in alcohol abstainers.. With this study, we show an inverse association between intake of vitamin C and the incidence of HNC and HNC-subtypes. Future research is recommended to investigate the underlying mechanisms and to confirm our results, which may be promising for the prevention of HNC.

Topics: Aged; Antioxidants; Ascorbic Acid; Carotenoids; Case-Control Studies; Cohort Studies; Diet; Dietary Supplements; Female; Follow-Up Studies; Head and Neck Neoplasms; Humans; Hypopharyngeal Neoplasms; Incidence; Laryngeal Neoplasms; Male; Middle Aged; Mouth Neoplasms; Netherlands; Oropharyngeal Neoplasms; Prospective Studies; Registries; Risk Factors; Vitamin E

The mainstay of the treatment of head and neck squamous cell carcinoma (HNSCC) is radiotherapy, which acts by producing free radicals. Therefore, this study was planned to observe the effect of radiotherapy on oxidative stress in patients of HNSCC.. This study was conducted on 50 histopathologically proven cases of HNSCC. The levels of nitric oxide, glutathione-S-transferase, and vitamin C were estimated colorimetrically before and after treatment in patients and in 30 age- and sex-matched healthy controls. The results were compared statistically.. The levels of nitric oxide and glutathione-S-transferase were significantly higher in patents as compared to controls and increased significantly after treatment. Vitamin C levels were significantly lower in patients as compared to controls and decreased significantly after treatment.. HNSCC leads to increased oxidative stress and treatment in the form of radiotherapy itself produces an accentuation of this stress.

Topics: Adult; Aged; Antioxidants; Ascorbic Acid; Carcinoma, Squamous Cell; Case-Control Studies; Female; Glutathione Transferase; Head and Neck Neoplasms; Humans; Male; Middle Aged; Neoplasm Staging; Nitric Oxide; Squamous Cell Carcinoma of Head and Neck; Young Adult

Head and neck squamous cell carcinomas (HNSCCs) are known for their aggressive growth and propensity to metastasize. The authors investigated the effect of a novel nutrient mixture (NM) containing ascorbic acid, lysine, proline, and green tea extract on human HNSCC cell line FaDu in vivo and in vitro. Athymic male nude mice (n = 12) were inoculated with 3 x 10(6) FaDu cells subcutaneously and randomly divided into 2 groups: group A was fed a regular diet and group B a regular diet supplemented with 0.5% NM. Four weeks later, the mice were sacrificed and their tumors were excised, weighted, and processed for histology. In vitro, FaDu cells were cultured in Dulbecco's modified Eagle's medium and exposed to NM at 0 to 1000 microg/mL in triplicate. Cell proliferation was assessed by MTT assay, matrix metalloproteinase (MMP) secretion by gelatinase zymography, invasion through Matrigel, apoptosis by live-green caspases, and cell morphology by hematoxylin-eosin staining. NM inhibited the growth of tumors by 55% (P = .0002) and exhibited dose-dependent toxicity on FaDu cells in vitro, with 53% (P = .0003) at 1000 microg/mL NM. Zymography revealed MMP-2 and phorbol 12-myristate 13-acetate-induced MMP-9 secretion. NM inhibited secretion of both MMPs in a dose-dependent manner, with virtual total inhibition at 1000 microg/mL. NM significantly inhibited FaDu invasion through Matrigel with total block at 1000 microg/mL. NM induced dose-dependent apoptosis. In conclusion, NM has therapeutic potential in the treatment of HNSCC by significantly suppressing tumor growth and significantly inhibiting MMP secretion and invasion of HNSCC cells in vitro.

Topics: Administration, Oral; Amino Acids; Animals; Apoptosis; Ascorbic Acid; Camellia sinensis; Carcinoma, Squamous Cell; Cell Line, Tumor; Cell Survival; Complementary Therapies; Food; Head and Neck Neoplasms; Humans; Male; Matrix Metalloproteinase 2; Matrix Metalloproteinase 9; Mice; Mice, Nude; Neoplasm Invasiveness; Plant Extracts; Tetradecanoylphorbol Acetate; Xenograft Model Antitumor Assays

Reactive oxygen species (ROS) and reactive nitrogen species (RNS) can function both as initiators and promoters in carcinogenesis. Antioxidants provide protection against cellular and molecular damage caused by ROS and RNS. We conducted a study to evaluate the levels of lipid peroxidation products, nitric oxide (NO) products and antioxidants in patients with head and neck squamous cell carcinoma (HNSCC). Fifty one HNSCC patients, 33 healthy tobacco smokers/chewers as tobacco user controls, and 37 non-smokers/chewers as normal controls were recruited for this study. Lipid peroxidation products, NO products and antioxidants were measured using spectrophotometric methods. Lipid peroxidation products, including lipid hydroperoxide (LHP) and malondialdehyde (MDA), nitric oxide (NO) products, including nitrite (NO(2)(-)), nitrate (NO(3)(-)), and total nitrite (TNO(2)(-)) were found to be significantly elevated with a concomitant depletion of antioxidants in HNSCC patients as compared to tobacco users and normal controls. These derangements were also evident albeit to a lesser degree in tobacco users as compared to normal controls. Results from this study demonstrate a potential involvement of both ROS and RNS in the pathogenesis of HNSCC and also illustrate the risk of ROS/RNS induced damage healthy tobacco users are exposed to, implicating their higher risk for upper aerodigestive tract cancer.

Topics: Adult; Aged; Aged, 80 and over; alpha-Tocopherol; Antioxidants; Ascorbic Acid; Carcinoma, Squamous Cell; Catalase; Female; Glutathione; Glutathione Peroxidase; Head and Neck Neoplasms; Humans; Lipid Peroxidation; Lipid Peroxides; Male; Malondialdehyde; Middle Aged; Nitrates; Nitric Oxide; Nitrites; Reactive Nitrogen Species; Reactive Oxygen Species; Smoking; Superoxides

To investigate and analyze changes in irradiated salivary gland function of patients with head and neck tumors treated with radiotherapy.. Thirty-seven patients with head and neck tumors, who received 40-70 Gy of irradiation to all major salivary glands, were analyzed. The weights of saliva secreted for 10 minutes at rest, and for 5 minutes with vitamin C stimulation, were measured. The salivary gland function was defined by the weight of saliva.. With vitamin C stimulation, the weight of saliva in patients whose doses were < or =50 Gy, was significantly higher than that of patients whose doses were > or = 58 Gy (2.48 +/- 0.33 g vs. 0.73 +/- 0.18 g, P = 0.0003). When doses administered to salivary glands were < or =50 Gy, the stimulated saliva secretion recovered over time, after irradiation. However, when the doses of irradiation were > or = 58 Gy, there was no recovery in saliva secretion even after a few years. Multiple regression analysis showed that age and chemotherapy may not affect salivary gland function even years after radiotherapy.. When salivary glands were irradiated with doses < or =50 Gy, gradual recovery of salivary gland function was observed over time, whereas there was no significant recovery when the irradiation dose was >58 Gy.

Topics: Adolescent; Adult; Aged; Ascorbic Acid; Carcinoma, Squamous Cell; Female; Head and Neck Neoplasms; Humans; Lymphoma, Non-Hodgkin; Male; Middle Aged; Radiotherapy Dosage; Saliva; Salivary Glands

The induction of apoptosis by the synthetic retinoid N-(4-hydroxyphenyl)retinamide (4HPR) has been documented in vitro in various cancer types. A role for reactive oxygen species (ROS) in apoptosis induced by 4HPR in some cancer cells has been demonstrated recently. We studied five different human head and neck and five lung cancer cell lines to determine whether the ROS play a general role in 4HPR-induced apoptosis. We found that 4HPR induced apoptosis in all of the cell lines; however, this effect was blocked by antioxidants in only 2 of the 10 cell lines. 4HPR induced a greater than 4-fold increase in the generation of intracellular ROS in these two cell lines compared with a much lower effect in other cell lines. Furthermore, these two cell lines were most sensitive to the induction of apoptosis by 4HPR. The level of the cellular antioxidant thiol and superoxide dismutase activity were relatively lower in cells, which responded to 4HPR with a high level of ROS generation. These results indicate that although ROS can mediate 4HPR-induced apoptosis in some cells, which may have a low endogenous cellular antioxidant levels, other mechanisms exist for 4HPR-induced apoptosis. One such mechanism may involve retinoic acid receptors (RARs) because an RAR antagonist was able to block partially 4HPR-induced apoptosis. In conclusion, 4HPR-induced apoptosis involves at least three different mechanisms, which are complex and can overlap in the same cell line: (a) one mechanism involving 4HPR-induced ROS; (b) one involving RARs; and (c) at least one that does not involve ROS or RARs and remains unclear.

Topics: Antineoplastic Agents; Antioxidants; Apoptosis; Ascorbic Acid; Carcinoma, Non-Small-Cell Lung; Carcinoma, Squamous Cell; Fenretinide; Head and Neck Neoplasms; Humans; Lung Neoplasms; Naphthalenes; Neoplasm Proteins; Oxidation-Reduction; Oxidative Stress; Reactive Oxygen Species; Receptors, Retinoic Acid; Sulfhydryl Compounds; Superoxide Dismutase; Tumor Cells, Cultured

The protective effects of ascorbic acid (AA), n-acetyl-l-cysteine (NAC), alpha-tocopherol acid (ATA), alpha-tocopherol-acid succinate (TAS), and 13-cis-retinoic acid (CRA) on mutagen-induced chromosomal breakage were studied. Mutagen-sensitivity was determined by the bleomycin assay in human lymphoblastoid cell lines (LCLs) and cultures of peripheral blood lymphocytes (PBLs) from head and neck cancer patients. Preincubation with chemopreventive agents statistically significantly decreased mutagen-induced chromatid breakage in LCLs and PBLs in a dose-related manner. As the concentration of the agents was increased in tenfold increments in the study range, mean breakage rates were reduced by 3.0 to 7.7% in LCLs and by 6.0 to 11.1% in PBLs. The effective concentrations are comparable to those achieved in clinical applications and found in human dietary studies. A similar phenomenon in vivo, if identified, may explain the differences in occurrence of head and neck and other cancers between populations with different dietary habits. The bleomycin assay may be used for studying compounds with presumed chemopreventive properties.

Topics: Acetylcysteine; Anticarcinogenic Agents; Antimutagenic Agents; Ascorbic Acid; Bleomycin; Cell Line; Chromosome Aberrations; Head and Neck Neoplasms; Humans; Lymphocytes; Tretinoin; Vitamin E

The protective effect of N-acetyl-L-cysteine (NAC) and ascorbic acid on mutagen-induced chromosomal breakage was determined using human lymphoblastoid cell lines as well as freshly cultured lymphocytes from patients with head and neck malignancies and healthy control subjects. Mutagen sensitivity was determined using the previously described bleomycin exposure assay. The toxicities of different concentrations of NAC and ascorbic acid, as well as both the preincubation and dose-dependent protective effects of these two agents, were analyzed. Both test drugs proved to be effective in diminishing mutagen-induced chromatid breakage in established lymphocyte cell lines. In freshly cultured lymphocytes, NAC given in doses ranging from 0.1 to 10 mmol/L decreased the number of mutagen-induced breaks per cell in a range from 23% to 73%, and ascorbic acid decreased chromosomal breakage by 21% to 58% in a dose range from 0.01 to 1 mmol/L. The results of this study demonstrate the protective effect mediated in vitro by both NAC and ascorbic acid against mutagen-induced chromosomal damage. A similar in vivo phenomenon may explain the differences in occurrence of head and neck cancer between populations with different dietary backgrounds.

Topics: Acetylcysteine; Ascorbic Acid; Bleomycin; Cell Line; Chromosome Fragility; Dose-Response Relationship, Drug; Drug Screening Assays, Antitumor; Head and Neck Neoplasms; Humans; In Vitro Techniques; Lymphocytes; Tumor Cells, Cultured

It is considered the radioprotective effect of ascorbic acid in patients with head and neck cancer. It is observed a reduction of yatrogenic effects over oral structures secondary to radiotherapy. It is recommended the oral administration of ascorbic acid in this type of patients.

Topics: Ascorbic Acid; Head and Neck Neoplasms; Humans; Mouth Diseases; Radiation Injuries; Radiation-Protective Agents