ascorbic-acid and Adenocarcinoma

Although some epidemiological studies have reported the associations between vitamin C and risk of esophageal cancer, these results are inconsistent. Therefore, we performed an updated meta-analysis to explore the associations between dietary vitamin C intake and risk of esophageal cancer. We used PubMed, Embase, and the Web of Science to screen all published articles, which yielded 18 papers eligible for data extraction (involving 4,126 cases and 36,902 controls), and then pooled the odds ratios (ORs) and corresponding 95% confidence intervals (CIs) using random-effects model. As we detected the associations in highest category and the lowest type of dietary vitamin C intake, we discovered that dietary vitamin C intake was negatively correlated to the risk of esophageal cancer. The analysis of subgroup showed a significant counter proportion between vitamin C and the risk of ESCC and EAC. Moreover, the dose-analysis indicated that if increasing dietary intake of vitamin C of 50 mg/day, esophageal cancer risk dropped down 10% (OR = 0.81, 95%CI: 0.75-0.87). In summary, our study provides a comprehensive and updated epidemiological evidence to elucidate the relationships between dietary vitamin C and reduction of esophageal cancer risk. Nevertheless, we still need larger case-control and cohort studies to confirm these connections.

Topics: Adenocarcinoma; Ascorbic Acid; Diet; Esophageal Neoplasms; Humans; Nutritional Status; Risk Factors; Vitamins

Barrett's esophagus (BE) is a well-established risk factor for esophageal adenocarcinoma. Our objective was to investigate the effectiveness of lifestyle interventions on BE risk.. We searched PubMed, Embase, and Web of Science up to 30 September 2020. The summary relative risks (RRs) and 95% confidence intervals (CIs) for the highest versus lowest categories of exposure were assessed. Analyses of subgroup, dose-response, sensitivity, and publication bias were conducted.. Sixty-two studies were included that involved more than 250,157 participants and 22,608 cases. Seven lifestyle factors were investigated: smoking, alcohol, body mass index (BMI), physical activity, sleep time, medication, and diet. We observed statistically significant increased BE risks for smoking (RR = 1.35, 95% CI = 1.16-1.57), alcohol intake (RR = 1.23, 95% CI = 1.13-1.34), body fatness (RR = 1.08, 95% CI = 1.03-1.13), less sleep time (RR = 1.76, 95% CI = 1.24-2.49), and proton pump inhibitors use (RR = 1.64, 95% CI = 1.17-2.29). Reduced risks of BE were found for aspirin (RR = 0.70, 95% CI = 0.58-0.84) and the intake of vitamin C (RR = 0.59, 95% CI = 0.44-0.80), folate (RR = 0.47, 95% CI = 0.31-0.71), and fiber (RR = 0.95, 95% CI = 0.93-0.97). The quality of most included studies was high and the subgroup analysis according to the quality score showed significant results (p < 0.05). There was no publication bias for smoking and alcohol. Although the analysis suggested significant evidence of publication bias for BMI, sensitivity analysis showed that the changes in the recalculated RRs were not significant.. The large meta-analysis revealed that lifestyle modifications could reduce the risks of BE and, consequently, esophageal adenocarcinoma.

Topics: Adenocarcinoma; Alcohol Drinking; Anti-Inflammatory Agents, Non-Steroidal; Ascorbic Acid; Aspirin; Barrett Esophagus; Body Mass Index; Confidence Intervals; Diet; Dietary Fiber; Esophageal Neoplasms; Exercise; Folic Acid; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Life Style; Proton Pump Inhibitors; Publication Bias; Risk; Sleep; Smoking

Although there is increasing evidence that vitamins influence pancreatic adenocarcinoma biology and carcinogenesis, a comprehensive review is lacking. In this study, we performed a PubMed literature search to review the anticancer mechanisms and the preclinical and clinical studies that support the development of the bioactive vitamins A, C, D, E, and K in pancreatic cancer intervention. Preclinical studies have shown promising results for vitamin A in pancreatic cancer prevention, with clinical trials showing intriguing responses in combination with immunotherapy. For vitamin C, preclinical studies have shown slower tumor growth rates and/or increased survival when used alone or in combination with gemcitabine, with clinical trials with this combination revealing decreased primary tumor sizes and improved performance status. Preclinical studies with vitamin D analogues have shown potent antiproliferative effects and repression of migration and invasion of pancreatic cancer cells, with a clinical trial showing increased time to progression when calciferol was added to docetaxel. For vitamin E, preclinical studies have shown that δ-tocotrienol and γ-tocotrienol inhibited tumor cell growth and survival and augmented gemcitabine activity. Early-phase clinical trials with δ-tocotrienol are ongoing. Vitamin K demonstrates activation of apoptosis and inhibition of cellular growth in pancreatic tumor cells; however, there are no clinical studies available for further evaluation. Although preclinical and clinical studies are encouraging, randomized controlled trials with endpoints based on insights gained from mechanistic and preclinical studies and early-phase clinical trials are required to determine the efficacy of bioactive vitamin interventions in pancreatic cancer.

Topics: Adenocarcinoma; Apoptosis; Ascorbic Acid; Cell Proliferation; Combined Modality Therapy; Dietary Supplements; Humans; Neoplasm Invasiveness; Pancreatic Neoplasms; Survival Rate; Vitamin A; Vitamin D; Vitamin E; Vitamin K; Vitamins

Ascorbic acid, as one of the important water-soluble vitamins, is essential for a range of physiological functions, including the syntheses of collagen, carnitine and neurotransmitters. It is also an important dietary antioxidant against oxidative stress. Current information suggests that vitamin C might be protective against the development of gastric cancer. Chronic infection with Helicobacter pylori is recognized to be a significant cause of gastric adenocarcinoma. Inflammation induced by H. pylori infection in the stomach not only causes significantly enhanced consumption of vitamin C, but also reduces secretion of the vitamin into the gastric lumen. Most of the evidence relating to vitamin C and H. pylori infection derives from clinical studies and experiments directly examining the effect of vitamin C on H. pylori-associated gastric carcinogenesis and remains limited. Furthermore, results from recent studies suggest that vitamin C might also increase the risk of cancer through its pro-oxidant activity and protect against oxidative stress in cancer cells through its antioxidant action. In this article we review recent publications on vitamin C research and assess the potential roles of vitamin C in H. pylori associated gastric carcinogenesis. The possible adverse effects of the vitamin C are also discussed.

Topics: Adenocarcinoma; Animals; Antioxidants; Ascorbic Acid; Gastric Mucosa; Helicobacter Infections; Helicobacter pylori; Humans; Oxidative Stress; Risk Factors; Stomach Neoplasms; T-Lymphocytes

Topics: Adenocarcinoma; Animals; Ascorbic Acid; Colonic Neoplasms; Humans; Male; Rats; Rectal Neoplasms

The aim of this study was to evaluate the effect of vitamin E and supragingival scaling with vitamin C on the salivary glands of patients with differentiated thyroid carcinoma after 131I treatment.. A total of 89 prospective patients with differentiated thyroid carcinoma were enrolled and randomly divided into the following groups: vitamin E group (n = 30, group A), vitamin C group (n = 30, group B) and supragingival scaling with vitamin C group (n = 29, group C). Using functional indices (e.g. maximum uptake fraction, uptake index, excretion fraction, secretion time and excretion rate), changes in the salivary gland functions before and a month after 131I treatment were assessed by dynamic imaging of salivary gland.. We compared the before and after 131I therapy results of the three groups. In group A (P  < 0.05), the excretion fraction and excretion rate of the left parotid gland were significantly higher, and the uptake index of the bilateral submandibular glands was significantly lower. No significant changes in salivary gland functional parameters were observed in group B (P > 0.05). The uptake index of the bilateral parotid glands and the excretion rate of the left parotid gland were significantly higher in group C (P < 0.05). The degree of serum amylase level reduction decreased significantly in group C (P < 0.05).. Vitamin E showed a protective effect on parotid excretion function in patients with differentiated thyroid carcinoma who underwent 131I treatment. Supragingival scaling may be a promising radiation protector because it is associated with a protective effect on the salivary gland functions.

Topics: Adenocarcinoma; Ascorbic Acid; Dental Scaling; Humans; Iodine Radioisotopes; Parotid Gland; Prospective Studies; Salivary Glands; Thyroid Neoplasms; Vitamin E

Treatment with high-dose intravenous (IV) ascorbic acid (AA) is used in complementary and alternative medicine for various conditions including cancer. Cytotoxicity to cancer cell lines has been observed with millimolar concentrations of AA. Little is known about the pharmacokinetics of high-dose IV AA. The purpose of this study was to assess the basic kinetic variables in human beings over a relevant AA dosing interval for proper design of future clinical trials. Ten patients with metastatic prostate cancer were treated for 4 weeks with fixed AA doses of 5, 30 and 60 g. AA was measured consecutively in plasma and indicated first-order elimination kinetics throughout the dosing range with supra-physiological concentrations. The target dose of 60 g AA IV produced a peak plasma AA concentration of 20.3 mM. Elimination half-life was 1.87 hr (mean, S.D. ± 0.40), volume of distribution 0.19 L/kg (S.D. ±0.05) and clearance rate 6.02 L/hr (100 mL/min). No differences in pharmacokinetic parameters were observed between weeks/doses. A relatively fast first-order elimination with half-life of about 2 hr makes it impossible to maintain AA concentrations in the potential cytotoxic range after infusion stop in prostate cancer patients with normal kidney function. We propose a regimen with a bolus loading followed by a maintenance infusion based on the calculated clearance.

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Area Under Curve; Ascorbic Acid; Half-Life; Humans; Male; Middle Aged; Neoplasm Metastasis; Prostatic Neoplasms; Vitamins

Treatment for pancreatic cancer with pharmacological ascorbate (ascorbic acid, vitamin C) decreases tumor progression in preclinical models. A phase I clinical trial was performed to establish safety and tolerability of pharmacological ascorbate combined with gemcitabine in patients with biopsy-proven stage IV pancreatic adenocarcinoma.. Nine subjects received twice-weekly intravenous ascorbate (15-125 g) employing Simon's accelerated titration design to achieve a targeted post-infusion plasma level of ≥350 mg/dL (≥20 mM). Subjects received concurrent gemcitabine. Disease burden, weight, performance status, hematologic and metabolic laboratories, time to progression and overall survival were monitored.. Mean plasma ascorbate trough levels were significantly higher than baseline (1.46 ± 0.02 vs. 0.78 ± 0.09 mg/dL, i.e., 83 vs. 44 μM, p < 0.001). Adverse events attributable to the drug combination were rare and included diarrhea (n = 4) and dry mouth (n = 6). Dose-limiting criteria were not met for this study. Mean survival of subjects completing at least two cycles (8 weeks) of therapy was 13 ± 2 months.. Data suggest pharmacologic ascorbate administered concurrently with gemcitabine is well tolerated. Initial data from this small sampling suggest some efficacy. Further studies powered to determine efficacy should be conducted.

Topics: Adenocarcinoma; Aged; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Antioxidants; Ascorbic Acid; Chromatography, High Pressure Liquid; Deoxycytidine; Disease-Free Survival; Drug Administration Schedule; Female; Gemcitabine; Glutathione; Humans; Infusions, Intravenous; Male; Middle Aged; Pancreatic Neoplasms; Patient Compliance; Patient Safety; Sentinel Lymph Node Biopsy

This paper aims at evaluating the impact of vitamins intake in the prevention of gastroesophageal reflux disease (GERD), Barrett's oesophagus (BE), and oesophageal adenocarcinoma (EADC). It concentrates primarily on the antioxidant vitamins A, C and E. There were 180 subjects included in the trial, 109 males and 71 females, which were divided in the four groups (70 patients with GERD, 20 patients with BE, 20 patients with EADC, and 70 healthy examinees composing a control group). Their antioxidant vitamins intake was investigated through the usage of the dietary questionnaires. Concentration of the mentioned antioxidant vitamin in serum was detected by HPLC method, and although there were no major statistical differences in their levels between four groups, there existed a correlation between the vitamin serum concentration and the rephlux disease degree. The results showed that the healthy examinees had consumed the greater quantities of the vitamins A, C and E, through both the natural (fruits and vegetables) and the supplementary (industrial vitamin additives) way, than the patients with GERD, BE and EADC. This was reflected in the higher serum levels of the mentioned vitamins in the first group in the comparison with the second group. Based on this, the intake of the vitamins A, C and E through both the natural and the supplementary ways is suggested in order to prevent the development of the GERD, BE and EADC.

Topics: Adenocarcinoma; Adolescent; Adult; Aged; Aged, 80 and over; Ascorbic Acid; Barrett Esophagus; Esophageal Neoplasms; Female; Gastroesophageal Reflux; Humans; Male; Middle Aged; Vitamin A; Vitamin E; Vitamins; Young Adult

The incidence of adenocarcinoma of the esophagus is increasing in most Western industrialized nations especially in white males. The impact of vitamins on the development of squamous cell carcinoma (SCC) and adenocarcinoma (AC) of the esophagus has not been elucidated. The goal of this pilot-study was to analyze the influence of daily vitamin consumption on the frequency of esophageal carcinoma in Germany.. Ninety-nine patients (males) with esophageal carcinoma (52 with SCC and 47 with AC) were compared to a control group of 50 randomly selected males from the Cologne area. Using a computer program to record the data, patients and controls were questioned in detail about their dietary habits. The interaction between known risk factors and the influence of vitamins on esophageal tumor risk were analyzed using logistic regression analysis.. The univariate analysis showed a significant risk reduction with increased intake of beta-carotene, vitamin C, vitamin E, and folic acid for both AC and for SCC. The results of logistic regression analysis were compatible with the known risk factors for SCC (alcohol and tobacco) and for AC (obesity, tobacco, and alcohol) and showed a significant risk reduction with an intake of vitamin E greater than 13 mg/day (RR=0.13, 95% CI=0.1-0.5, P=0.0004) and vitamin C greater than 100 mg/day (RR=0.33, 95% CI=0.11-0.92, P=0.034) for patients with SCC and similar results for patients with AC.. Our data showed that low intake of vitamin C and E correlates significantly with the development of squamous cell carcinoma as well as adenocarcinoma of the esophagus in males. The relevance of interaction of vitamins with other dietary factors, alcohol, and tobacco are topics of current research.

Topics: Adenocarcinoma; Adult; Alcohol Drinking; Ascorbic Acid; Body Mass Index; Carcinoma, Squamous Cell; Case-Control Studies; Dietary Supplements; Esophageal Neoplasms; Folic Acid; Germany; Humans; Incidence; Male; Pilot Projects; Risk Factors; Smoking; Surveys and Questionnaires; Vitamin A; Vitamin E

A randomized nutrition intervention trial was conducted among 29,584 adult residents of Linxian, China, to examine the effects of vitamin/mineral supplementation on the occurrence of esophageal/gastric cardia cancer in this high-risk population. A fractional factorial study design allowed evaluations of four different combinations of nutrients: (A) retinol and zinc; (B) riboflavin and niacin; (C) vitamin C and molybdenum; and (D) beta-carotene, vitamin E, and selenium. During the 5.25-year intervention, significant reductions in total mortality, total cancer mortality, and stomach cancer mortality occurred among those receiving beta-carotene, vitamin E, and selenium. At the end of intervention, an endoscopic survey was carried out in a sample of subjects to see if the nutritional supplements had affected the prevalence of clinically silent precancerous lesions and early invasive cancers of the esophagus or stomach. Endoscopy was performed on 391 individuals from two study villages. The prevalences of esophageal and gastric dysplasia and cancer were compared by nutrient factor. Cancer or dysplasia was diagnosed in 15% of the participants. No statistically significant reductions in the prevalence of esophageal or gastric dysplasia or cancer were seen for any of the four vitamin/mineral combinations. The greatest reduction in risk (odds ratio, 0.38; P = 0.09) was seen for the effect of retinol and zinc on the prevalence of gastric cancer. Although no significant protective effects were seen in this endoscopic survey, there was a suggestion that supplementation with retinol and zinc may protect against the development of gastric neoplasia in this high-risk population. Additional studies with larger numbers of endpoints will be needed to further evaluate this possibility.

Topics: Adenocarcinoma; Adult; Aged; Ascorbic Acid; beta Carotene; Carotenoids; Cell Transformation, Neoplastic; China; Cross-Cultural Comparison; Cross-Sectional Studies; Double-Blind Method; Endoscopy, Gastrointestinal; Esophageal Neoplasms; Esophagus; Female; Gastric Mucosa; Humans; Incidence; Male; Middle Aged; Minerals; Molybdenum; Niacin; Precancerous Conditions; Riboflavin; Rural Population; Selenium; Stomach Neoplasms; Survival Rate; Vitamin A; Vitamin E; Vitamins; Zinc

Linxian, China has some of the highest rates of esophageal/gastric cardia cancer in the world, and epidemiological evidence suggests that chronically low intake of micronutrients may contribute to these high cancer rates. To examine whether supplementation with multiple vitamins and minerals can affect the occurrence of esophageal/gastric cardia cancer in this population, a two-arm randomized nutrition intervention trial was conducted among 3318 Linxian residents with cytological evidence of esophageal dysplasia. During the 6-year intervention, esophageal/gastric cardia cancer mortality was 8% lower among those receiving the active supplements. After 30 and 72 months of intervention, endoscopic surveys were carried out to see if the nutritional supplements had affected the prevalence of clinically silent precancerous lesions and early invasive cancers of the esophagus and stomach. In the first survey, in 1987, 833 subjects were endoscoped; in the second survey, in 1991, 396 subjects were examined. The histological diagnoses from each survey were compared by treatment group. Cancer or dysplasia was diagnosed in 28% of the subjects endoscoped in 1987 and 24% of those examined in 1991. The odds ratio for subjects in the treatment group (versus those in the placebo group) having esophageal or gastric dysplasia or cancer was 0.84 (95% confidence interval, 0.61-1.15) in 1987 and 0.86 (0.54-1.38) in 1991. Although modest protective effects on worst overall diagnosis were seen in the supplemented group in both surveys, none of the results was statistically significant, and the findings must be considered inconclusive.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adenocarcinoma; Adult; Aged; Ascorbic Acid; beta Carotene; Carotenoids; Cell Transformation, Neoplastic; Cross-Cultural Comparison; Double-Blind Method; Endoscopy, Gastrointestinal; Esophageal Neoplasms; Esophagus; Female; Follow-Up Studies; Gastric Mucosa; Humans; Male; Middle Aged; Minerals; Molybdenum; Niacin; Precancerous Conditions; Riboflavin; Rural Population; Selenium; Stomach Neoplasms; Survival Rate; Vitamin A; Vitamin E; Vitamins; Zinc

Pancreatic carcinoma is one of the most aggressive cancers overcoming chemoresistance. Thus, novel compounds to complement the current antitumor agents are in need. Ocoxin oral solution (OOS) has proven antioxidant, anti-inflammatory, and antistromagenic properties. The aim of this study was to analyze the effect of OOS in an experimental pancreatic cancer model and its implication in stroma-related chemoresistance to paclitaxel and gemcitabine.. Murine pancreatic carcinoma 266-6 cells were treated with OOS to analyze cell cycle and to perform a mRNA comparative microarray study. Then the viability was assessed in combination with paclitaxel and/or gemcitabine. Chemoresistance induced by the medium taken from fibroblast cultures was also investigated on 6 human pancreatic carcinoma cell lines. Furthermore, an experimental model of pancreatic cancer was carried out to study the effect of OOS in vivo.. Ocoxin oral solution enhances the cytotoxic effect of paclitaxel and gemcitabine, while it ameliorates the chemoresistance induced by fibroblast-derived soluble factors in human pancreatic cancer cells. The OOS also promotes the regulation of the expression of genes that are altered in pancreatic carcinoma and slows down 266-6 cell pancreatic tumor development in vivo.. Ocoxin oral solution could be a potential complement to the chemotherapeutic drugs for pancreatic adenocarcinoma.

Topics: Adenocarcinoma; Administration, Oral; Animals; Antineoplastic Agents; Ascorbic Acid; Cell Cycle; Cell Line; Cell Line, Tumor; Cell Survival; Deoxycytidine; Drug Resistance, Neoplasm; Folic Acid; Gemcitabine; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Humans; Male; Mice, Inbred C57BL; Neoplasms, Experimental; Paclitaxel; Pancreatic Neoplasms; Pantothenic Acid; Plant Extracts; Solutions; Vitamin B 12; Vitamin B 6; Zinc Sulfate

HIF-1α is a transcriptional regulator that functions in the adaptation of cells to hypoxic conditions; it strongly impacts the prognosis of patients with cancer. High-dose, intravenous, pharmacological ascorbate (P-AscH

Topics: Adenocarcinoma; Animals; Ascorbic Acid; Cell Hypoxia; Cell Line, Tumor; Cell Proliferation; Cell Survival; Disease Progression; Dose-Response Relationship, Drug; Humans; Hydrogen Peroxide; Hypoxia-Inducible Factor 1, alpha Subunit; Mice; Mice, Nude; Neoplasm Metastasis; Pancreatic Neoplasms; Prolyl Hydroxylases; Protein Processing, Post-Translational; Vascular Endothelial Growth Factor A

Gastric adenocarcinoma most often presents at an advanced stage and overall five-year survival of ∼30%. Pharmacological ascorbate (high-dose IV ascorbate) has been proposed as a promising nontoxic adjuvant to standard radio-chemotherapies in several cancer types. In the current study, pharmacological ascorbate (0.5-2 m M) caused a dose-dependent decrease (70-85% at 2 m M) in clonogenic survival of gastric adenocarcinoma cells (AGS and MNK-45), but was relatively nontoxic to a small intestinal epithelial nonimmortalized human cell isolate (FHs 74 Int). The addition of pharmacological ascorbate (1 m M) to standard radio-chemotherapies [i.e., 5-FU (5 μ M); cisplatin (0.5 μ M); irinotecan (2.5 μ M); carboplatin (5 μ M); paclitaxel (2-4 n M); and X rays (1.8 Gy)] also potentiated gastric cancer clonogenic cell killing [additional decreases were noted with: ascorbate plus 5-FU/radiation (1%); ascorbate plus cisplatin/irinotecan (9-19%); and ascorbate plus paclitaxel/carboplatin (6-7%)]. The gastric cancer cell toxicity and chemosensitization seen with pharmacological ascorbate was dependent on H

Topics: Adenocarcinoma; Animals; Ascorbic Acid; Cell Line, Tumor; Chemoradiotherapy; Dose-Response Relationship, Drug; Dose-Response Relationship, Radiation; Drug Synergism; Female; Humans; Mice; Stomach Neoplasms; Xenograft Model Antitumor Assays

Nanoscaled electrode has been attracting increasing attention because of striking fundamentals and practical applications. Usually, the nanoscaled electrode is fabricated by manual or photo or electron-beam lithography, which is not easy to reproducibly fabricate with simple equipment. In this paper, a cost-effective method, nanoskiving, is developed to fabricate an ultralong nanowire electrode (ULNE). The ULNE is reproducibly obtained by simply sectioning a sandwich epoxy block with a Au film. The width of ULNE could be down to nanometer dependence on the thickness of the Au film, while the length could reach to the millimeter. Thus, the created Au ULNE shows steady-state microamperometric current, characteristic of the nanoelectrode array attributed to its macroscopic length and nanoscaled width without considering the overlap of the diffusion layer of the neighboring nanoelectrode. The electrodeposited Pt/Au ULNE displays unusual electrocatalytic performance toward both the oxidation and reduction of hydrogen peroxide and, as a nanosensor, gives rise to high sensitivity and selectivity of monitoring hydrogen peroxide released from cells stimulated by ascorbic acid.

Topics: Adenocarcinoma; Ascorbic Acid; Electrochemical Techniques; Electrodes; Gold; Humans; Hydrogen Peroxide; MCF-7 Cells; Nanotechnology

Photodynamic therapy (PDT) uses light, photosensitizer molecules and oxygen to generate reactive oxygen species (ROS) that kill cancer cells. Redaporfin, a new photosensitizer in clinical trials, generates both singlet oxygen and superoxide ions. We report the potentiation of redaporfin-PDT in combination with ascorbate and with the inhibition of antioxidant enzymes in A549 (human lung adenocarcinoma) and CT26 (mouse colon adenocarcinoma) cells. The addition of ascorbate and the inhibition of superoxide dismutase (SOD) strongly increased the phototoxicity of redaporfin towards A549 cells but not towards CT26 cells. The inhibition of catalase and the depletion of the glutathione pool also potentiate redaporfin-PDT towards A549 cells. The lower SOD activity of A549 cells might explain this difference. SOD activity levels may be explored to increase the selectivity and efficacy of PDT with photosensitizers that generate radical species.

Topics: A549 Cells; Adenocarcinoma; Adenocarcinoma of Lung; Animals; Antioxidants; Ascorbic Acid; Cell Line, Tumor; Cell Survival; Humans; Hydrogen Peroxide; Light; Lung Neoplasms; Mice; Oxidative Stress; Photochemotherapy; Photosensitizing Agents; Porphyrins; Reactive Oxygen Species; Sulfonamides; Superoxide Dismutase

Studying different concentrations of nickel smelting smoke subjects of human lung adenocarcinoma cells (A549) carcinogenic effects, discusses the influence of L-ascorbic acid protection.. The A549 cells were divided into experimental and L-ascorbic acid in the intervention group. Plus exposure group concentration of nickel refining dusts were formulated 0.00, 6.25, 12.50, 25.00, 50.00, 100.00 µg/ml suspension, the intervention group on the basis of the added exposure group containing L-ascorbic acid (100 mmol/L), contact 24 h. Detection of cell viability by MTT assay. When the test substance concentration select 0.00, 25.00, 50.00, 100.00 µg/ml experiment for internal Flou-3 fluorescent probe to detect cell Ca²⁺ concentration, within DCFH-DA detect intracellular reactive oxygen (ROS) content, real-time quantitative PCR (real time, in the RT-PCR) was used to detect cell HIF-1α gene expression.. With the increase of concentration, subjects increased cell growth inhibition rate, intracellular Ca²⁺ concentration increases, ROS content increased, HIF-1α gene expression increased, differences were statistically significant (P < 0.05). After L-ascorbic acid intervention treatment, the results of the intervention group were lower than that of the experimental group, and the difference was statistically significant (P < 0.05), so L-ascorbic acid can effectively protect the nickel exposure damage to cells.. With subjects following exposure to nickel concentration increased, its effect on A549 cell damage increases, L-ascorbic acid cell damage caused by nickel has certain protective effect.

Topics: Adenocarcinoma; Adenocarcinoma of Lung; Ascorbic Acid; Calcium; Cell Line, Tumor; Cell Survival; Culture Media; Humans; Hypoxia-Inducible Factor 1, alpha Subunit; Lung Neoplasms; Metallurgy; Nickel; Occupational Exposure; Protective Agents; Reactive Oxygen Species; Smoke

Several N-nitroso compounds (NOC) have been shown to be carcinogenic in a variety of laboratory animals, but evidence of their carcinogenicity in humans is lacking. We aimed to examine the association between NOC intake and colorectal cancer (CRC) risk and possible effect modification by vitamins C and E and protein in a large case-control study carried out in Newfoundland and Labrador and Ontario, Canada. A total of 1760 case patients with pathologically confirmed adenocarcinoma and 2481 population controls were asked to complete a self-administered FFQ to evaluate their dietary intakes 1 year before diagnosis (for cases) or interview (for controls). Adjusted OR and 95 % CI were calculated across the quintiles of NOC (measured by N-nitrosodimethylamine (NDMA)) intake and relevant food items using unconditional logistic regression. NDMA intake was found to be associated with a higher risk of CRC (highest v. lowest quintiles: OR 1·42, 95 % CI 1·03, 1·96; P for trend = 0·005), specifically for rectal carcinoma (OR 1·61, 95 % CI 1·11, 2·35; P for trend = 0·01). CRC risk also increased with the consumption of NDMA-containing meats when the highest tertile was compared with the lowest tertile (OR 1·47, 95 % CI 1·03, 2·10; P for trend = 0·20). There was evidence of effect modification between dietary vitamin E and NDMA. Individuals with high NDMA and low vitamin E intakes had a significantly increased risk than those with both low NDMA and low vitamin E intakes (OR 3·01, 95 % CI 1·43, 6·51; P for interaction = 0·017). The present results support the hypothesis that NOC intake may be positively associated with CRC risk in humans. Vitamin E, which inhibits nitrosation, could modify the effect of NDMA on CRC risk.

Topics: Adenocarcinoma; Adult; Aged; Ascorbic Acid; Case-Control Studies; Colorectal Neoplasms; Diet; Dietary Proteins; Dimethylnitrosamine; Female; Humans; Logistic Models; Male; Meat; Middle Aged; Newfoundland and Labrador; Nitroso Compounds; Ontario; Rectal Neoplasms; Risk Factors; Surveys and Questionnaires; Vitamin E

Scanning (SEM) and transmission electron microscopy (TEM) were used to characterize the cytotoxic effects of ascorbate (VC), menadione (VK3), or a VC:VK3 combination on a human prostate carcinoma cell line (DU145) following a 1-h vitamin treatment and a subsequent 24-h incubation in culture medium. Cell alterations examined by light and electron microscopy were treatment-dependent with VC + VK3 >VK3 > VC > Sham. Oxidative stress-induced damage was found in most organelles. This report describes injuries in the tumor cell nucleus (chromatin and nucleolus), mitochondria, endomembranes, lysosomal bodies (autophagocytoses) and inclusions. Morphologic alterations suggest that cytoskeleton damage is likely responsible for the superficial cytoplasmic changes, including major changes in cell shape and size and the self-excising phenomena. Unlike apoptotic bodies, the excised pieces contain ribonucleoproteins, but not organelles. These deleterious events cause a progressive, significant reduction in the tumor cell size. During nuclear alterations, the nuclei maintain their envelope during chromatolysis and karyolysis until cell death, while nucleoli undergo a characteristic segregation of their components. In addition, changes in fat and glycogen storage are consistent the cytotoxic and metabolic alterations caused by the respective treatments. All cellular ultrastructural changes are consistent with cell death by autoschizis and not apoptosis or other kinds of cell death.

Topics: Adenocarcinoma; Ascorbic Acid; Cell Death; Cell Line, Tumor; Cell Nucleus; Cytoskeleton; Humans; Male; Microscopy, Electron; Organelles; Prostatic Neoplasms; Vitamin K 3

The aim of the paper was to determine the level of antioxidants and metabolomic fingerprinting in both raw beetroots and naturally fermented beetroot juices from organic (ORG) versus conventional (CONV) production. In addition, the anticancer properties of the fermented beetroot juices were evaluated.. The obtained results showed that ORG fresh beetroots contained significantly more dry matter, vitamin C and some individual phenolic compounds than CONV beetroots. The content of total phenolic acids was significantly higher in CONV beetroots compared with the ORG ones. The level of flavonoids was similar in ORG and CONV beetroots. There were only slight differences in the chemical composition of ORG and CONV beetroot juices. Metabolomic analysis provided a possibility to distinguish clearly between ORG and CONV fermented beetroot juices. However, this method was less useful in the case of fresh whole beetroots. It was found that anticancer activity was stronger in the case of ORG fermented juices when compared with CONV ones.. The obtained results indicate that ORG- and CONV-produced beetroots and fermented beetroot juices have different chemical properties and different impacts on cancer cells. It is necessary to continue research on this topic in order to confirm and understand the achieved results.

Topics: Adenocarcinoma; Anticarcinogenic Agents; Antioxidants; Apoptosis; Ascorbic Acid; Beta vulgaris; Beverages; Cell Line, Tumor; Chromatography, High Pressure Liquid; Fermentation; Flavonoids; Food Inspection; Food, Organic; Humans; Metabolome; Phenols; Plant Roots; Poland; Spectrometry, Mass, Electrospray Ionization; Stomach Neoplasms

Tea polyphenols (-)-epigallocatechin-3-gallate (EGCG) and theaflavin-3-3'-digallate (TF3) are two prospective compounds in cancer prevention and treatment. Ascorbic acid (Vc) is essential to a healthy diet as well as being a highly effective antioxidant. In this work, the effects of the combination of EGCG or TF3 with Vc on the apoptosis and caspases-3/9 activities in human lung adenocarcinoma SPC-A-1 cells and esophageal carcinoma Eca-109 cells were determined. Furthermore, the role of mitogen-activated protein kinases (MAPK) pathways in the apoptosis induced by TF3 or EGCG together with Vc were studied using three MAPK inhibitors (ERK inhibitor PD98059, JNK inhibitor SP600125 and p38 inhibitor SB203580). Our results showed that Vc could enhance the EGCG and TF3 induced apoptosis in SPC-A-1 and Eca-109 cells, and this effect involved the activation of caspase-3 and 9. EGCG, TF3 and Vc could activate MAPK pathways respectively, and each compound activated different MAPK subfamilies in different cells. This may explain the enhancement of EGCG and TF3 induced apoptosis by Vc in SPC-A-1 and Eca-109 cells, and will ultimately aid the design of more effective anti-cancer treatments.

Topics: Adenocarcinoma; Anticarcinogenic Agents; Antineoplastic Agents; Apoptosis; Ascorbic Acid; Biflavonoids; Caspase 3; Caspase 9; Catechin; Cell Line, Tumor; Enzyme Inhibitors; Esophageal Neoplasms; Gallic Acid; Gene Expression Regulation, Enzymologic; Gene Expression Regulation, Neoplastic; Humans; Lung Neoplasms; MAP Kinase Signaling System

While dietary antioxidants are emerging as potentially modifiable risk factors for esophageal adenocarcinoma (EAC), studies on dietary antioxidants and its precursor Barrett's esophagus (BE) are limited. The present study extends previous work on BE by investigating risks of nondysplastic BE, dysplastic BE and EAC associated with intake of antioxidants such as vitamin C, vitamin E, β-carotene, and selenium. Age and sex matched control subjects (n=577 for BE; n=1,507 for EAC) were sampled from an Australian population register. Information on demography, and well established EAC risk factors were obtained using self-administered questionnaires. Intake of antioxidants for patients newly diagnosed with nondysplastic BE (n=266), dysplastic BE (n=101), or EAC (n=299), aged 18-79 years, were obtained using a food frequency questionnaire. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using multivariable adjusted logistic regression models. High intake of β-carotene from food and supplement sources combined was inversely associated with risk of dysplastic BE (OR Q4 vs. Q1=0.45; 95%CI: 0.20-1.00). High intake of vitamin E from food sources (OR Q4 vs. Q1=0.43; 95%CI: 0.28-0.67), from food and supplements combined (OR Q4 vs. Q1=0.64; 95%CI: 0.43-0.96), and a high antioxidant index score were inversely associated with risk of EAC. We found no significant trends between intake of β-carotene, vitamin C, vitamin E, and selenium and risk of nondysplastic or dysplastic BE. However, our data suggest that a high intake of β-carotene may be associated with decreased risk of dysplastic BE.

Topics: Adenocarcinoma; Adult; Aged; Antioxidants; Ascorbic Acid; Australia; Barrett Esophagus; beta Carotene; Energy Intake; Esophageal Neoplasms; Feeding Behavior; Female; Fruit; Humans; Male; Middle Aged; Risk Factors; Selenium; Vegetables; Vitamin E

Vitamin C exists in two forms: the reduced (ascorbic acid--AA) and oxidized form (dehydroascorbic acid--DHA). This is a nutrient whose benefits are long known and widely publicized, being most of them related to its antioxidant action. As an antioxidant, the main role of vitamin C is to neutralize free radicals, reducing oxidative stress. However, some controversial studies suggest that this nutrient may have a preventive and therapeutic role in cancer disease due to their possible pro-oxidant activity, promoting the formation of reactive oxygen species that can induce cell death in cancer cells. This factor, coupled with the decrease of antioxidant enzymes and increase of decompartmentalized transition metals in tumor cells may result in the selective cytotoxicity of vitamin C and the subsequent revelation of its therapeutic potential. In this way the first purpose of this work was radioactively label the reduced form of vitamin C with Tc-99m, its quality control by HPLC and the time stability. The second purpose was to use the radioactive complex 99mTc-AA in in vitro and in vivo studies in order to evaluate its uptake by colorectal cancer cells and biodistribution in mices, respectively. The results suggest that the pharmaceutical formulation developed, which was reproducible and stable over time, was residually taken up by colorectal cancer cells. Future studies are needed to deepen our understanding about the radioactive complex 99mTc-AA and clarify the mechanisms of action of vitamin C in oncologic disease.

Topics: Adenocarcinoma; Animals; Anticarcinogenic Agents; Antineoplastic Agents; Ascorbic Acid; Cell Line, Tumor; Colorectal Neoplasms; Isotope Labeling; Mice; Mice, Inbred BALB C; Mice, Nude; Organotechnetium Compounds; Radiopharmaceuticals; Xenograft Model Antitumor Assays

Sulfonamides of halogenated bacteriochlorins bearing Cl or F substituents in the ortho positions of the phenyl rings have adequate properties for photodynamic therapy, including strong absorption in the near-infrared (λ(max) ≈ 750 nm, ε ≈ 10(5) M(-1) cm(-1)), controlled photodecomposition, large cellular uptake, intracellular localization in the endoplasmic reticulum, low cytotoxicity, and high phototoxicity against A549 and S91 cells. The roles of type I and type II photochemical processes are assessed by singlet oxygen luminescence and intracellular hydroxyl radical detection. Phototoxicity of halogenated sulfonamide bacteriochlorins does not correlate with singlet oxygen quantum yields and must be mediated both by electron transfer (superoxide ion, hydroxyl radicals) and by energy transfer (singlet oxygen). The photodynamic efficacy is enhanced when cellular death is induced by both singlet oxygen and hydroxyl radicals.

Topics: Adenocarcinoma; Antioxidants; Ascorbic Acid; Cell Survival; Energy Transfer; Fluorescence; Humans; Hydroxyl Radical; In Vitro Techniques; Lung Neoplasms; Melanoma; Photochemotherapy; Photosensitizing Agents; Porphyrins; Reactive Oxygen Species; Singlet Oxygen; Tumor Cells, Cultured

Vitamin C, available in its reduced form (ascorbic acid; AA) and in its oxidized form (dehydroascorbic acid; DHA), may act in physiological conditions as an antioxidant or pro-oxidant. The aim of this study is to evaluate the cytotoxic effects of pharmacological doses of AA in a human colorectal adenocarcinoma cell line (WiDr) in vitro, through spectrophotometry, clonogenic assays and flow cytometry, and in vivo with xenotransplanted Balb/c nu/nu mice. The results show that the reduced form of vitamin C induces an anti-proliferative and cytotoxic effect in adenocarcinoma colorectal cells under study. The results obtained in vivo after treatment with AA showed a large reduction in the rate of tumor growth. Such understanding can guide decisions about which colorectal cancer patients might potentially benefit from vitamin C pharmacologic therapy.

Topics: Adenocarcinoma; Animals; Antineoplastic Agents; Antioxidants; Ascorbic Acid; Cell Line, Tumor; Cell Proliferation; Cell Survival; Colorectal Neoplasms; Dehydroascorbic Acid; Flow Cytometry; Glutathione; Humans; Mice; Mice, Inbred BALB C; Mitochondrial Membranes; Spectrophotometry; Tumor Stem Cell Assay

Topics: Adenocarcinoma; Administration, Oral; Animals; Antineoplastic Combined Chemotherapy Protocols; Ascorbic Acid; Deoxycytidine; Drug Synergism; Gemcitabine; Humans; Injections, Intravenous; Mice; Pancreatic Neoplasms; Treatment Outcome

Lysosomal photosensitizers have been used in photodynamic therapy. The combination of such photosensitizers and light causes lysosomal photodamage, inducing cell death. Lysosomal disruption can lead to apoptosis but its signaling pathways remain to be elucidated. In this study, N-aspartyl chlorin e6 (NPe6), an effective photosensitizer that preferentially accumulates in lysosomes, was used to study the mechanism of apoptosis caused by lysosomal photodamage. Apoptosis in living human lung adenocarcinoma cells (ASTC-a-1) after NPe6-photodynamic treatment (NPe6-PDT) was studied using real-time single-cell analysis. Our results demonstrated that NPe6-PDT induced rapid generation of reactive oxygen species (ROS). The photodynamically produced ROS caused a rapid destruction of lysosomes, leading to release of cathepsins, and the ROS scavengers vitamin C and NAC prevent the effects. Then the following spatiotemporal sequence of cellular events was observed during cell apoptosis: Bcl-2-associated X protein (Bax) activation, cytochrome c release, and caspase-9/-3 activation. Importantly, the activation of Bax proved to be a crucial event in this apoptotic machinery, because suppressing the endogenous Bax using siRNA could significantly inhibit cytochrome c release and caspase-9/-3 activation and protect the cell from death. In conclusion, this study demonstrates that PDT with lysosomal photosensitizer induces Bax activation and subsequently initiates the mitochondrial apoptotic pathway.

Topics: Adenocarcinoma; Adenocarcinoma of Lung; Apoptosis; Ascorbic Acid; bcl-2-Associated X Protein; Caspase 3; Caspase 9; Cathepsins; Cell Line, Tumor; Cytochromes c; Fluorescent Antibody Technique; Humans; Lung Neoplasms; Lysosomes; Microscopy, Confocal; Mitochondria; Photosensitizing Agents; Porphyrins; Reactive Oxygen Species; RNA Interference; RNA, Small Interfering

Over the last decade, epidemiological, experimental and clinical studies have implicated oxidative stress in the development and progression of prostate cancer. In the present study, we evaluated the oxidative status and antioxidant defense in patients with prostate cancer (PCa) taking into consideration: treatment, Gleason score and bone metastasis. For this, we measured concentrations of plasmatic thiobarbituric acid reactive substances (TBARS), serum protein carbonylation, whole blood catalase (CAT) and superoxide dismutase (SOD) activities, as well as the plasma and erythrocyte thiol levels and serum vitamin C and E concentration. This study was performed on 55 patients with PCa and 55 healthy men. TBARS levels and serum protein carbonylation were higher in PCa patients than in controls and altered levels of antioxidants were found in these patients. CAT activity was decreased and SOD activity was higher in PCa patients when compared with controls. Non-protein thiol levels were increased, however, serum vitamin C and vitamin E content were reduced in PCa patients when compared with controls. In addition, different parameters analyzed in PCa patients based on metastasis, treatment and Gleason score showed changes in oxidative stress biomarkers and antioxidant defenses. These findings may indicate an imbalance in the oxidant/antioxidant status, supporting the idea that oxidative stress plays a role in PCa, moreover, the oxidative profile appear to be modified by bone metastasis, treatment and Gleason score.

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Antineoplastic Agents, Hormonal; Ascorbic Acid; Bone Neoplasms; Catalase; Cyproterone Acetate; Erythrocytes; Goserelin; Humans; Lipid Peroxidation; Male; Middle Aged; Neoplasm Grading; Oxidative Stress; Prostatic Neoplasms; Protein Carbonylation; Sulfhydryl Compounds; Superoxide Dismutase; Thiobarbituric Acid Reactive Substances; Vitamin E

The incidence of esophageal adenocarcinoma in humans is increasing more rapidly than any other malignancy in the United States. Animal studies have demonstrated the efficacy of freeze-dried berry supplementation on carcinogen-induced esophageal squamous cell carcinoma in rats; however, no such studies have been done in esophagoduodenal anastomosis (EDA), an animal model for reflux-induced esophageal adenocarcinoma (EAC) development. Eight-week-old male Sprague-Dawley rats were randomized into 3 groups: EDA + control diet (EDA-CD; n = 10); EDA + 2.5% black raspberry diet (EDA-BRB; n = 11) and EDA + 2.5% blueberry diet (EDA-BB; n = 12). After 2 wk of feeding the respective diets, the rats underwent EDA surgery to induce gastroesophageal reflux and then continued the diet. Measurement of feed intake suggested that all EDA-operated animals had lower feed intake starting at 10 wk after surgery and this was significant close to termination at 24 wk. There were no significant differences in either reflux esophagitis (RE), intestinal metaplasia (IM) (70% in CD, 64% in BRB, and 66% in BB; P = 0.1) or EAC incidence (30% for CD, 34% for BRB, and 25% for BB; P = 0.2) with supplementation. Berry diets did not alter COX-2 levels, but BB diet significantly reduced MnSOD levels (1.23 ± 0.2) compared to control diet (2.05 ± 0.14; P < 0.05). We conclude that a dietary supplementation of freeze-dried BRB and BB at 2.5% (w/w) was not effective in the prevention of reflux-induced esophageal adenocarcinoma in this EDA animal model.

Topics: Adenocarcinoma; Anastomosis, Surgical; Animals; Anthocyanins; Ascorbic Acid; Biomarkers; Blueberry Plants; Cyclooxygenase 2; Dietary Supplements; Disease Models, Animal; Disease Progression; Esophageal Neoplasms; Esophagitis, Peptic; Esophagus; Food Handling; Freeze Drying; Fruit; Linear Models; Male; Plant Preparations; Rats; Rats, Sprague-Dawley; Selenium; Superoxide Dismutase; Weight Gain

Pharmacologic concentrations of ascorbate may be effective in cancer therapeutics. We hypothesized that ascorbate concentrations achievable with i.v. dosing would be cytotoxic in pancreatic cancer for which the 5-year survival is <3%.. Pancreatic cancer cell lines were treated with ascorbate (0, 5, or 10 mmol/L) for 1 hour, then viability and clonogenic survival were determined. Pancreatic tumor cells were delivered s.c. into the flank region of nude mice and allowed to grow at which time they were randomized to receive either ascorbate (4 g/kg) or osmotically equivalent saline (1 mol/L) i.p. for 2 weeks.. There was a time- and dose-dependent increase in measured H(2)O(2) production with increased concentrations of ascorbate. Ascorbate decreased viability in all pancreatic cancer cell lines but had no effect on an immortalized pancreatic ductal epithelial cell line. Ascorbate decreased clonogenic survival of the pancreatic cancer cell lines, which was reversed by treatment of cells with scavengers of H(2)O(2). Treatment with ascorbate induced a caspase-independent cell death that was associated with autophagy. In vivo, treatment with ascorbate inhibited tumor growth and prolonged survival.. These results show that pharmacologic doses of ascorbate, easily achievable in humans, may have potential for therapy in pancreatic cancer.

Topics: Adenocarcinoma; Animals; Ascorbic Acid; Cell Line, Tumor; Cell Survival; Cells, Cultured; Cytotoxins; Dose-Response Relationship, Drug; Humans; Hydrogen Peroxide; Mice; Mice, Nude; Oxidative Stress; Pancreatic Neoplasms; Signal Transduction; Xenograft Model Antitumor Assays

Tea polyphenols have been shown to have anticancer activity in many studies. In the present study, we investigated effects of theaflavin-3-3'-digallate (TF(3)), one of the major theaflavin monomers in black tea, in combination with ascorbic acid (AA), a reducing agent, and (-)-epigallocatechin-3-gallate (EGCG), the main polyphenol presented in green tea, in combination with AA on cellular viability and cell cycles of the human lung adenocarcinoma SPC-A-1 cells. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay showed that the 50% inhibition concentrations (IC(50)) of TF(3), EGCG, and AA on SPC-A-1 cells were 4.78, 4.90, and 30.62 micromol/L, respectively. The inhibitory rates of TF(3) combined with AA (TF(3)+AA) and EGCG combined with AA (EGCG+AA) at a molar ratio of 1:6 on SPC-A-1 cells were 54.4% and 45.5%, respectively. Flow cytometry analysis showed that TF(3)+AA and EGCG+AA obviously increased the cell population in the G(0)/G(1) phase of the SPC-A-1 cell cycle from 53.9% to 62.8% and 60.0%, respectively. TF(3)-treated cells exhibited 65.3% of the G(0)/G(1) phase at the concentration of its IC(50). Therefore, TF(3)+AA and EGCG+AA had synergistic inhibition effects on the proliferation of SPC-A-1 cells, and significantly held SPC-A-1 cells in G(0)/G(1) phase. The results suggest that the combination of TF(3) with AA or EGCG with AA enhances their anticancer activity.

Topics: Adenocarcinoma; Apoptosis; Ascorbic Acid; Cell Line, Tumor; Dose-Response Relationship, Drug; Flavonoids; Humans; Lethal Dose 50; Lung Neoplasms; Phenols; Plant Extracts; Polyphenols; Tea

The role of antioxidants in the pathogenesis of reflux esophagitis (RE), Barrett's esophagus (BE), and esophageal adenocarcinoma (EAC) remains unknown. We evaluated the associations among dietary antioxidant intake and these diseases. We performed an assessment of dietary antioxidant intake in a case control study of RE (n = 219), BE (n = 220), EAC (n = 224), and matched population controls (n = 256) (the Factors Influencing the Barrett's Adenocarcinoma Relationship study) using a modification of a validated FFQ. We found that overall antioxidant index, a measure of the combined intake of vitamin C, vitamin E, total carotenoids, and selenium, was associated with a reduced risk of EAC [odds ratio (OR) = 0.57; 95% CI = 0.33-0.98], but not BE (OR = 0.95; 95% CI = 0.53-1.71) or RE (OR = 1.60; 95% CI = 0.86-2.98), for those in the highest compared with lowest category of intake. Those in the highest category of vitamin C intake had a lower risk of EAC (OR = 0.37; 95% CI = 0.21-0.66; P-trend = 0.001) and RE (OR = 0.46; 95% CI = 0.24-0.90; P-trend = 0.03) compared with those in the lowest category. Vitamin C intake was not associated with BE, and intake of vitamin E, total carotenoids, zinc, copper, or selenium was not associated with EAC, BE, or RE. In conclusion, the overall antioxidant index was associated with a reduced risk of EAC. Higher dietary intake of vitamin C was associated with a reduced risk of EAC and RE. These results suggest that antioxidants may play a role in the pathogenesis of RE and EAC and may be more important in terms of progression rather than initiation of the disease process.

Topics: Adenocarcinoma; Aged; Antioxidants; Ascorbic Acid; Barrett Esophagus; Carotenoids; Case-Control Studies; Copper; Diet; Esophageal Neoplasms; Female; Gastroesophageal Reflux; Humans; Male; Middle Aged; Minerals; Odds Ratio; Risk Factors; Selenium; Vitamin E; Zinc

Berries and berry extracts possess properties that make them important in the prevention of cancer. The high antioxidant levels of these extracts play a role, but components of the berries can have other effects on cell replication and survival. We chose to test the hypothesis that (i) although the antioxidant capacity of raspberry extracts is important for inhibiting the proliferation of tumor cells, other characteristics of the berry extracts are responsible for a major part of their antiproliferative activity, and that (ii) the relative importance of the antioxidant effect can depend on the cell type being studied. The aim of this study was to assess the relative roles of low pH and high antioxidant levels in the killing of 3 cell types by an aqueous extract from Meeker red raspberries. Stomach, colon, and breast cancer cells were treated with berry extract and with HCl and ascorbic acid solutions of the same pH. A dilution of 7.5% ascorbic acid solution, of the same pH and slightly higher antioxidant concentration than the berry extract, killed less than 10% of the stomach and colon cancer cells. In contrast, the berry extract at this same dilution killed more than 90% of these cells. Antioxidants played a more significant role in the killing of breast cancer cells, however. For these cells, approximately 50% of the killing could be attributed to antioxidant effects. We conclude that the antioxidant effect plays a minor role in the killing of 2 gastrointestinal cell types, but its role in inactivating a breast cancer cell line is much more significant. No evidence of apoptosis was observed, and caspase activation did not contribute to cell killing by the extract.

Topics: Adenocarcinoma; Antioxidants; Ascorbic Acid; Breast Neoplasms; Caspases; Cell Division; Cell Line, Tumor; Colonic Neoplasms; Fruit; Humans; Phytotherapy; Plant Extracts; Stomach Neoplasms

Gastric cancer is a major health burden in the Asia-Pacific region but consensus on prevention strategies has been lacking. We aimed to critically evaluate strategies for preventing gastric cancer.. A multidisciplinary group developed consensus statements using a Delphi approach. Relevant data were presented, and the quality of evidence, strength of recommendation, and level of consensus were graded.. Helicobacter pylori infection is a necessary but not sufficient causal factor for non-cardia gastric adenocarcinoma. A high intake of salt is strongly associated with gastric cancer. Fresh fruits and vegetables are protective but the use of vitamins and other dietary supplements does not prevent gastric cancer. Host-bacterial interaction in H. pylori infection results in different patterns of gastritis and differences in gastric acid secretion which determine disease outcome. A positive family history of gastric cancer is an important risk factor. Low serum pepsinogens reflect gastric atrophy and may be useful as a marker to identify populations at high risk for gastric cancer. H. pylori screening and treatment is a recommended gastric cancer risk reduction strategy in high-risk populations. H. pylori screening and treatment is most effective before atrophic gastritis has developed. It does not exclude the existing practice of gastric cancer surveillance in high-risk populations. In populations at low risk for gastric cancer, H. pylori screening is not recommended. First-line treatment of H. pylori infection should be in accordance with national treatment guidelines.. A strategy of H. pylori screening and eradication in high-risk populations will probably reduce gastric cancer incidence, and based on current evidence is recommended by consensus.

Topics: Adenocarcinoma; Anti-Bacterial Agents; Anticarcinogenic Agents; Ascorbic Acid; Asia; Biomarkers, Tumor; Dietary Supplements; Evidence-Based Medicine; Fruit; Genetic Predisposition to Disease; Helicobacter Infections; Helicobacter pylori; Humans; Incidence; Mass Screening; Pacific Islands; Pedigree; Pepsinogens; Prevalence; Risk Assessment; Risk Factors; Sodium Chloride, Dietary; Stomach Neoplasms; Vegetables; Vitamins

The incidence of esophageal adenocarcinoma (EA) and its precursor condition, Barrett's esophagus, has risen rapidly in the United States for reasons that are not fully understood. Therefore, we evaluated the association between use of supplemental vitamins and minerals and risk of neoplastic progression of Barrett's esophagus and EA. The Seattle Barrett's Esophagus Program is a prospective study based on 339 men and women with histologically confirmed Barrett's esophagus. Participants underwent baseline and periodic follow-up exams, which included endoscopy and self-administered questionnaires on diet, supplement use, and lifestyle characteristics. Use of multivitamins and 4 individual supplements was calculated using time-weighted averages of reported use over the observational period. Cox proportional-hazards models were used to calculate hazard ratios (HR) for each endpoint: EA, tetraploidy, and aneuploidy. During a mean follow-up of 5 yr, there were 37 cases of EA, 42 cases of tetraploidy, and 34 cases of aneuploidy. After controlling for multiple covariates including diet, nonsteroidal anti-inflammatory drug use, obesity, and smoking, participants who took 1 or more multivitamin pills/day had a significantly decreased risk of tetraploidy [HR = 0.19; 95% confidence interval (CI) = 0.08-0.47) and EA (HR = 0.38; 95% CI = 0.15-0.99] compared to those not taking multivitamins. Significant inverse associations were also observed between risk of EA and supplemental vitamin C (> or = 250 mg vs. none: HR = 0.25; 95% CI = 0.11-0.58) and vitamin E (> or = 180 mg vs. none: HR = 0.25; 95% CI = 0.10-0.60). In this cohort study, use of multivitamins and single antioxidant supplements was associated with a significantly reduced risk of EA and markers of neoplastic progression among individuals with Barrett's esophagus.

Topics: Adenocarcinoma; Adult; Aged; Aneuploidy; Ascorbic Acid; Barrett Esophagus; Cell Transformation, Neoplastic; Chemoprevention; Cohort Studies; Dietary Supplements; Disease Progression; Drug Therapy, Combination; Endoscopy; Esophageal Neoplasms; Female; Flow Cytometry; Follow-Up Studies; Humans; Male; Middle Aged; Proportional Hazards Models; Prospective Studies; Risk Factors; Vitamin E; Vitamins

Bile acids are often refluxed into the lower oesophagus and are candidate carcinogens in the development of oesophageal adenocarcinoma. We show here that the secondary bile acid, deoxycholic acid (DCA), is the only one of the commonly refluxed bile acids tested here, to show genotoxicity, in terms of chromosome damage and mutation induction in the human p53 gene. This genotoxicity was apparent at both neutral and acidic pH, whilst there was a considerable increase in bile-induced toxicity at acidic pH. The higher levels of cell death and low cell survival rates at acidic pH may imply that acid bile exposure is toxic rather than carcinogenic, as dead cells do not seed cancer development. We also show that DCA (at neutral and acid pH) induced the release of reactive oxygen species (ROS) within the cytoplasm of exposed cells. We further demonstrate that the genotoxicity of DCA is ROS mediated, as micronucleus induction was significantly reduced when cells were treated with DCA + the anti-oxidant vitamin C. In conclusion, we show that DCA, is an effective genotoxin at both neutral and acidic pH. As bile acids like DCA can induce DNA damage at neutral pH, suppressing the acidity of the refluxate will not completely remove its carcinogenic potential. The genotoxicity of DCA is however, ROS dependent, hence anti-oxidant supplementation, in addition to acid suppression may block DCA driven carcinogenesis in Barrett's patients.

Topics: Adenocarcinoma; Antioxidants; Ascorbic Acid; Barrett Esophagus; Carcinoma, Squamous Cell; Cell Survival; Deoxycholic Acid; Detergents; DNA Damage; Esophageal Neoplasms; Humans; Hydrogen-Ion Concentration; Micronucleus Tests; Reactive Oxygen Species; Tumor Cells, Cultured; Tumor Suppressor Protein p53

Cancer is associated with increased cell growth, and expression of matrix metalloproteinases (MMPs) and transforming growth factor-beta (TGF-beta). The dose-dependent effects of ascorbate (Vitamin C) on cancer cell growth, and expression of MMPs and TGF-beta were examined. Renal-adenocarcinoma, melanoma and mammary cancer cells were dosed with 0-100mM ascorbate and examined for cell survival or proliferation, and expression of MMP-1, MMP-2 and TGF-beta at protein and/or mRNA levels. The lower concentrations of ascorbate significantly inhibited cancer cell viability while stimulating MMPs and TGF-beta expression, indicating elimination of cancer cells with damage to the extracellular matrix (ECM). Conversely, ascorbate at higher concentrations dramatically stimulated cell proliferation and inhibited MMPs and TGF-beta expression, implicating growth and ECM advantage.

Topics: Adenocarcinoma; Antioxidants; Ascorbic Acid; Breast Neoplasms; Cell Survival; Enzyme-Linked Immunosorbent Assay; Extracellular Matrix; Humans; Kidney Neoplasms; Matrix Metalloproteinase 1; Matrix Metalloproteinase 2; Melanoma; RNA, Messenger; Skin Neoplasms; Transforming Growth Factor beta1; Tumor Cells, Cultured

The luminal microenvironment including acid and nitric oxide (NO) has been implicated in Barrett's esophagus carcinogenesis. We investigated the ability of acid and NO to induce DNA damage in esophageal cells.. Transformed and primary Barrett's esophagus and adenocarcinoma cells were exposed to either acid, (pH 3.5), +/- antioxidant or NO from a donor or generated by acidification of nitrite in the presence of ascorbate +/- NO scavenger. Phosphorylation of histone H2AX and the neutral comet assay were used to detect DNA double-strand breaks (DSBs). Intracellular levels of reactive oxygen species and NO were detected with fluorescent dyes. Mitochondrial viability was measured with a rhodamine dye. Long-term survival was assessed by clonogenic assay.. Exposure to acid (pH 3.5) for > or =15 minutes induced DSBs in all cell lines (P < .05). There was a concomitant increase in intracellular reactive oxygen species in the absence of mitochondrial damage, and pretreatment with antioxidants inhibited DNA damage. Exposure to physiologic concentrations of NO produced from the NO donor or acidification of salivary nitrite induced DSBs in a dose- (>25 micromol/L) and cell-dependent manner (adenocarcinoma >Barrett's esophagus, P < .05). This occurred preferentially in S-phase cells consistent with stalled replication forks and was blocked with a NO scavenger. NO also induced DSBs in primary Barrett's esophagus cells treated ex vivo. Cells were able to survive when exposed to acid and NO.. Both acid and NO have the potential to generate DSBs in the esophagus and via distinct mechanisms.

Topics: Adenocarcinoma; Antioxidants; Ascorbic Acid; Barrett Esophagus; Cell Line, Tumor; Cell Survival; Cell Transformation, Neoplastic; Comet Assay; DNA Breaks, Single-Stranded; Dose-Response Relationship, Drug; Esophageal Neoplasms; Gastric Acid; Histones; Humans; Hydrazines; Hydrogen-Ion Concentration; Mitochondria; Nitric Oxide; Nitric Oxide Donors; Phosphorylation; Reactive Oxygen Species; S Phase; Sodium Nitrite; Time Factors

The risk of gastric cancer (GC) associated with dietary intake of nitrosodimethylamine (NDMA) and endogenous formation of nitroso compounds (NOCs) was investigated in the European Prospective Investigation into Cancer and Nutrition (EPIC). The study included 521,457 individuals and 314 incident cases of GC that had occurred after 6.6 average years of follow-up. An index of endogenous NOC (ENOC) formation was estimated using data of the iron content from meat intake and faecal apparent total NOC formation according to previous published studies. Antibodies to Helicobacter pylori and vitamin C levels were measured in a sub-sample of cases and matched controls included in a nested case-control within the cohort. Exposure to NDMA was < 1 microg on average compared with 93 mug on average from ENOC. There was no association between NDMA intake and GC risk (HR, 1.00; 95% CI, 0.7-1.43). ENOC was significantly associated with non-cardia cancer risk (HR, 1.42; 95% CI, 1.14-1.78 for an increase of 40 microg/day) but not with cardia cancer (HR, 0.96; 95% CI, 0.69-1.33). Although the number of not infected cases is low, our data suggest a possible interaction between ENOC and H.pylori infection (P for interaction = 0.09). Moreover, we observed an interaction between plasma vitamin C and ENOC (P < 0.02). ENOC formation may account for our previously reported association between red and processed meat consumption and gastric cancer risk.

Topics: Adenocarcinoma; Animals; Ascorbic Acid; Case-Control Studies; Cattle; Diet; Dimethylnitrosamine; Europe; Female; Helicobacter Infections; Helicobacter pylori; Humans; Iron; Male; Meat; Middle Aged; Nitrosamines; Prospective Studies; Risk Factors; Stomach Neoplasms

The high incidence of lung cancer and ineffective toxic action of current mono and doublet chemotherapy approaches result in poor patient survival. Further, matrix metalloproteinases (MMPs) are implicated in neoplastic invasion and metastasis. Based on this, the authors investigated the effect of a dietary micronutrient mixture (NM) containing lysine, proline, arginine, ascorbic acid, and green tea extract on the tumor growth of human lung carcinoma cell A-549 xenografts in athymic nude mice. Additionally, the authors tested the in vitro antitumor effect of NM on lung carcinoma A-549 cells by measuring cell proliferation by MTT assay, MMP-2 and -9 secretion by gelatinase zymography, and cell invasion through Matrigel. Nutrient supplementation strongly suppressed the growth of tumors without adverse effects in nude mice; tumor weight was reduced by 44% (P = .0001) and tumor burden was reduced by 47% (P < .0001) with supplementation. Zymography demonstrated in vitro secretion of MMP-2 by uninduced human lung carcinoma cells and both MMP-2 and -9 by phorbol 12-mysristate 13-acetate (PMA) (200 ng/mL)-treated cells. NM inhibited the secretion of both MMPs in a dose-dependent fashion, with virtual total inhibition at 500 microg/mL concentration. The invasion of human lung carcinoma cells through Matrigel was significantly reduced at 100 microg/mL (64%) and totally inhibited at 500 microg/mL concentration of NM (P = .01). Suppression of lung tumor growth in nude mice and inhibition of MMP secretion and Matrigel invasion suggest NM may act as an anticancer agent and as such warrants further investigation.

Topics: Adenocarcinoma; Animals; Antineoplastic Combined Chemotherapy Protocols; Ascorbic Acid; Camellia sinensis; Cell Line, Tumor; Cell Movement; Cell Proliferation; Collagen; Dietary Supplements; Dose-Response Relationship, Drug; Drug Combinations; Drug Screening Assays, Antitumor; Humans; Laminin; Lung Neoplasms; Lysine; Mice; Mice, Nude; Plant Extracts; Proline; Proteoglycans

To examine the role of six flavonoid classes (flavanones, flavan-3-ols, flavonols, flavones, anthocyanidins and isoflavones) and vitamin C in the aetiology of stomach cancer.. Case-control study undertaken in Greece in the 1980s. Dietary information was obtained from 110 patients with incident stomach adenocarcinoma and 100 control patients. Flavonoid estimates were based on the recently released database of the US Department of Agriculture.. In models including sociodemographic variables, energy intake, vegetables, fruits and, alternatively, vitamin C the six flavonoid classes, only flavanones and vegetables remained significantly inversely associated with stomach cancer risk. The odds ratio (95% confidence intervals) per one standard deviation increase of intake of flavanones was 0.55 (0.31-0.96) whereas for vitamin C it was 1.05 (0.46-2.41). When fruits and vegetables were not adjusted for, both vitamin C and several flavonoid categories were inversely associated with stomach cancer risk, but these associations could be attributed to other compounds in these foods.. Among the major flavonoid classes studied, only flavanone intake is inversely associated with stomach cancer risk and could account for the apparent protective effect of fruit intake against this form of cancer. Additional factors, however, are likely to be involved in the consistent protection conveyed by vegetables.

Topics: Adenocarcinoma; Antioxidants; Ascorbic Acid; Case-Control Studies; Diet; Female; Flavanones; Flavonoids; Fruit; Humans; Male; Middle Aged; Odds Ratio; Stomach Neoplasms; Vegetables

To study biologic effects of increased manganese superoxide dismutase (MnSOD) on cell behavior, we overexpressed MnSOD in a human prostate cancer cell line RWPE-2 by cDNA transfection. Stable transfectants of MnSOD showed a two- to threefold increase in MnSOD protein and enzymatic activity and a decrease in growth rate with prolonged cell population doubling times. Western blot analysis showed a 1.5- to twofold increase in the cyclin-dependent kinase inhibitor p21(Waf1) in MnSOD transfectants. Overexpression of MnSOD resulted in a seven- to eightfold increase in reduced glutathione (GSH), 18- to 26-fold increase in oxidized glutathione (GSSG), and a two- to threefold decrease in the ratio of GSH to GSSG. MnSOD-overexpressing cells showed an increase in sensitivity to the cytotoxicity of buthionine sulfoximine, a glutathione-depleting agent, and vitamin C, but a decrease in sensitivity to sodium selenite. Treatment with a superoxide dismutase (SOD) mimic MnTMPyP resulted in similar effects of MnSOD overexpression on cell responses to vitamin C and selenium. These data demonstrate that overexpression of MnSOD or treatment with SOD mimics can result in antioxidant or prooxidant effects in cells, depending on the presence of other antioxidants and prooxidants. MnSOD also has redox regulatory effects on cell growth and gene expression. These findings suggest that MnSOD and SOD mimics have the potential for cancer prevention or treatment.

Topics: Adenocarcinoma; Animals; Antioxidants; Ascorbic Acid; Blotting, Western; Cell Line, Tumor; Cell Proliferation; Cyclin-Dependent Kinase Inhibitor p21; Cyclins; DNA, Complementary; Dose-Response Relationship, Drug; Glutathione; Glutathione Peroxidase; Humans; Male; Oxidants; Oxidation-Reduction; Oxidative Stress; Oxygen; Phenotype; Plasmids; Prostatic Neoplasms; Rats; Sodium Selenite; Superoxide Dismutase; Tetrazolium Salts; Thiazoles; Transfection

Hypoxia-inducible factor (HIF) plays an important role in determining patterns of gene expression in cancer. HIF is down-regulated in oxygenated cells by a series of Fe (II) and 2-oxoglutarate dependent dioxygenases that hydroxylate specific residues in the regulatory HIF-alpha subunits. Because these enzymes require ascorbate for activity in vitro we analyzed the effects of ascorbate on HIF in human cancer cell lines. Ascorbate at physiological concentrations (25 micro M) strikingly suppressed HIF-1alpha protein levels and HIF transcriptional targets, particularly when the system was oncogenically activated in normoxic cells. Similar results were obtained with iron supplementation. These results indicate that both ascorbate and iron availability have major effects on HIF, and imply that the system is commonly regulated by limiting hydroxylase activity under normoxic tissue culture conditions.

Topics: Adenocarcinoma; Ascorbic Acid; Breast Neoplasms; Cell Hypoxia; Endothelial Growth Factors; Female; Ferrous Compounds; Glucose Transporter Type 1; Humans; Hypoxia-Inducible Factor 1, alpha Subunit; Intercellular Signaling Peptides and Proteins; Lymphokines; Male; Monosaccharide Transport Proteins; Neoplasms; Ovarian Neoplasms; Procollagen-Proline Dioxygenase; Prostatic Neoplasms; RNA, Messenger; Transcription Factors; Transcriptional Activation; Transferrin; Tumor Cells, Cultured; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factors

To examine the effects of vitamin C (VC) on androgen receptor (AR)-mediated functions in a human prostate cancer cell line, Los Angeles prostate cancer (LAPC-4). VC is an essential dietary substance in the maintenance and preservation of vital functions in humans. However, the role of VC in prostate cancer remains to be elucidated.. Cell proliferation and the expression of two well-known androgen regulated proteins, prostate-specific antigen and human glandular kallikrein-2, were studied in the presence of VC.. In the presence of androgen and VC, both cell growth and the expression of prostate-specific antigen and human glandular kallikrein-2 proteins were decreased. Moreover, AR-mediated transcription activity of the prostate-specific antigen gene was suppressed with VC, similar to the phenomenon observed when cells were treated with hydrogen peroxide. These effects were reversed with catalase. However, additional studies did not reveal changes in the expression level of AR protein or its androgen-binding activity with the addition of VC.. The results of our study suggest that the pro-oxidant property of VC might be one of the mechanisms by which it modulates AR-mediated function in LAPC-4 cells.

Topics: Adenocarcinoma; Androgens; Anticarcinogenic Agents; Ascorbic Acid; Cell Differentiation; Cell Division; Gene Expression Regulation, Neoplastic; Genes, Reporter; Humans; Male; Neoplasm Proteins; Neoplasms, Hormone-Dependent; Prostate-Specific Antigen; Prostatic Neoplasms; Receptors, Androgen; Tissue Kallikreins; Transcription, Genetic; Transfection; Tumor Cells, Cultured

To correlate the extent of lipid peroxidation with the antioxidant status in the circulation of patients with fibroadenoma and adenocarcinoma of the breast.. Ten fibroadenoma and thirty breast cancer patients and an equal number of age- and sex- matched normal subjects were chosen for the study. Lipid peroxidation as evidenced by thiobarbituric acid reactive substances (TBARS) and the status of the antioxidants superoxide dismutase (SOD), catalase (CAT), reduced glutathione (GSH), glutathione peroxidase (GPx), glutathione S-transferase (GST) ascorbic acid and vitamin E were estimated.. Enhanced lipid peroxidation with concomitant depletion of antioxidants was observed in breast cancer patients as compared to normal subjects and fibroadenoma patients (p < 0.05). A similar pattern of changes was seen in fibroadenoma patients as compared to corresponding normal subjects (p < 0.05).. This study has revealed an imbalance in the redox status in patients with fibroadenoma and adenocarcinoma of the breast.

Topics: Adenocarcinoma; Adolescent; Adult; Antioxidants; Ascorbic Acid; Breast Neoplasms; Catalase; Erythrocytes; Female; Fibroadenoma; Glutathione; Glutathione Peroxidase; Glutathione Transferase; Humans; Lipid Peroxidation; Middle Aged; Oxidation-Reduction; Superoxide Dismutase; Thiobarbituric Acid Reactive Substances; Vitamin E

Alkaline phosphatase (ALP) refers to a group of nonspecific phosphomonoesterases located primarily in cell plasma membrane. It has been described in different cell lines that ecto-ALP is directly or indirectly involved in the modulation of organic cation transport. We aimed to investigate, in Caco-2 cells, a putative modulation of 1-methyl-4-phenylpyridinium (MPP(+)) apical uptake by an ecto-ALP activity. Ecto-ALP activity and (3)H-MPP(+) uptake were evaluated in intact Caco-2 cells (human colon adenocarcinoma cell line), in the absence and presence of a series of drugs. The activity of membrane-bound ecto-ALP expressed on the apical surface of Caco-2 cells was studied at physiological pH using p-nitrophenylphosphate as substrate. The results showed that Caco-2 cells express ALP activity, characterized by an ecto-oriented active site functional at physiological pH. Genistein (250 micro M), 3-isobutyl-1-methylxanthine (1 mM), verapamil (100 micro M), and ascorbic acid (1 mM) significantly increased ecto-ALP activity and decreased (3)H-MPP(+) apical transport in this cell line. Orthovanadate (100 micro M) showed no effect on (3)H-MPP(+) transport and on ecto-ALP activity. On the other hand, okadaic acid (310 nM) and all trans-retinoic acid (1 micro M) significantly increased (3)H-MPP(+) uptake and inhibited ecto-ALP activity. There is a negative correlation between the effect of drugs upon ecto-ALP activity and (3)H-MPP(+) apical transport (r = -0.9; P = 0.0014). We suggest that apical uptake of organic cations in Caco-2 cells is affected by phosphorylation/dephosphorylation mechanisms, and that ecto-ALP activity may be involved in this process.

Topics: Adenocarcinoma; Alkaline Phosphatase; Antioxidants; Ascorbic Acid; Caco-2 Cells; Cations; Cell Membrane; Colonic Neoplasms; Dose-Response Relationship, Drug; Humans; Phosphoric Monoester Hydrolases; Protein Transport; Tretinoin; Tumor Cells, Cultured; Up-Regulation; Vanadates

Gastric juice vitamin C may be protective against gastric carcinogenesis but concentrations are significantly reduced by Helicobacter pylori infection. We investigated the in vitro effects of vitamin C at concentrations comparable with those found in gastric juice on gastric cancer cells and H pylori.. Gastric cancer cell lines and various H pylori strains were treated with L-ascorbic acid for up to 72 hours. Cell viability, and protein and DNA synthesis were determined. Flow cytometry was used for assessment of H pylori adherence, cell cycle distribution, and apoptosis. H pylori growth and its haemagglutination activity were determined using viability count and microtitration assay.. Vitamin C induced a significant dose dependent growth inhibition of gastric AGS and MKN45 cells but this effect was significantly reduced at levels similar to those in gastric juice of H pylori infected patients (<50 microM). Although vitamin C had no obvious effect on H pylori growth, haemagglutination activity, or adherence ability to gastric AGS cells compared with untreated controls, it significantly enhanced H pylori associated apoptosis and induced cell cycle arrest in these cells.. Vitamin C may inhibit gastric cancer cell growth and alter H pylori induced cell cycle events at concentrations comparable with those in gastric juice, but has no effect on H pylori growth or pathogenicity. However, the inhibitory effect on gastric cancer cells was lost at vitamin C concentrations found in patients with H pylori infection.

Topics: Adenocarcinoma; Ascorbic Acid; Bacterial Adhesion; Cell Division; Flow Cytometry; Gastric Juice; Helicobacter Infections; Helicobacter pylori; Hemagglutination; Hemagglutination Tests; Humans; Hydrogen-Ion Concentration; Intestinal Mucosa; Stomach Neoplasms; Tumor Cells, Cultured

Patients with advanced cancer exhibit multifaceted defects in their immune capacity, which are likely to contribute to an increased susceptibility to infections and disease progression and to constitute a barrier to immunotherapeutic interventions. A chronic inflammatory condition associated with increased oxidative stress has been suggested as one of the responsible mechanisms behind the tumor-induced immune suppression. We, therefore, speculated that supplementation with the antioxidant vitamin E could enhance the immune functions in patients with advanced cancer.. This hypothesis was here tested in twelve patients with colorectal cancer (Dukes' C and D) who, prior to intervention with chemo- or radiotherapy, received a daily dose of 750 mg of vitamin E during a period of 2 weeks.. Short-term supplementation with high doses of dietary vitamin E leads to increased CD4:CD8 ratios and to enhanced capacity by their T cells to produce the T helper 1 cytokines interleukin 2 and IFN-gamma. In 10 of 12 patients, an increase of 10% or more (average, 22%) in the number of T cells producing interleukin 2 was seen after 2 weeks of vitamin E supplementation, as compared with peripheral blood monocyte samples taken before treatment (P = 0.02). Interestingly, there seemed to be a more pronounced stimulatory effect by vitamin E on naïve (CD45RA(+)) T helper cells as compared with T cells with a memory/activated phenotype.. Dietary vitamin E may be used to improve the immune functions in patients with advanced cancer, as a supplement to more specific immune interventions.

Topics: Adenocarcinoma; Aged; Antigens, CD; Antioxidants; Ascorbic Acid; CD4-CD8 Ratio; Colorectal Neoplasms; Dietary Supplements; Flow Cytometry; Humans; Immunity, Cellular; Interferon-gamma; Interleukin-2; Middle Aged; Neoplasm Staging; Th1 Cells; Time Factors; Vitamin E

Binary systems combining a transition metal complex and ascorbate have been proposed recently for catalytic therapy of malignant tumors. The killing effect on tumor cells is achieved by production of free radicals in the course of accelerated oxidation of ascorbate by dioxygen in the presence of transition metal complexes. Further progress in the development of binary catalytic systems (BCSs) requires a special method for their investigation in cells and tissues, because neither component of BCSs fluoresces. Here a resonance Raman confocal spectral imaging (RR CSI) technique was introduced as a unique approach to monitor quantitatively the transition metal complexes within living cells. Intracellular accumulation, localization, and retention of theraphthal (TP), a catalyst of the advanced TP/ascorbate BCS, were investigated in A549 cells with the RR CSI technique. The cellular analysis was complemented with the detailed study of molecular interactions of TP in solution and environmental factors affecting the RR spectrum of TP. TP does not penetrate into membranes, it binds very weakly to DNA and RNA, but it readily forms complexes with proteins. Binding with Ca(2+) cations and decreasing pH below 6 induce aggregation of TP. By analyzing RR spectra recorded from every point within a TP-treated cell, three states of the agent were discriminated, namely, monomeric TP in polar environment, TP bound to proteins, and aggregated TP. Their cytoplasmic and nuclear distributions were mapped at different stages of uptake and efflux. By introducing organelle-selective fluorescent probes into drug-treated cells and measuring intracellular localization of both the probe and the drug, compartmentation of TP was revealed. Cell growth suppression by the TP/ascorbate system was measured, and probable molecular and organelle targets of radical damage were characterized.

Topics: Adenocarcinoma; Ascorbic Acid; Cell Division; Cell Survival; Humans; Indoles; Lung Neoplasms; Microscopy, Confocal; Spectrum Analysis, Raman; Tumor Cells, Cultured

In spite of diverging incidence trends, subsite, and subtype-specific gastric cancer data on the association with dietary antioxidants are sparse. We aimed to test whether the apparent protective effect of antioxidants is mainly confined to noncardia (distal) cancer of the intestinal subtype, to which most of the incidence decline in gastric cancer has been ascribed. In a Swedish study base (total population 1.3 million), we interviewed 567 cases uniformly classified to subsite (cardia vs. noncardia) and subtype (intestinal vs. diffuse), and 1165 population-based controls, frequency matched for age and sex. Serologic data on H. pylori status was available for a subset of 542 individuals. Ascorbic acid (vitamin C) was inversely associated with all subsites and subtypes of gastric cancer in a significant dose-response manner (all p<0.05), with risk reductions between 40% and 60%. beta-carotene was also strongly and negatively associated with risk, particularly with the intestinal type. The associations with alpha-tocopherol (vitamin E) were less clear. The highest parallel intake of all three antioxidants (quartiles 4), compared to those with the lowest parallel intakes (quartiles 1), was associated with a 70% lower risk of developing noncardia cancer (OR 0.3, 95% CI 0.1-0.9). Our results suggest that antioxidants might be especially beneficial among subjects at increased risk for gastric cancer such as smokers and those infected by H. pylori. We conclude that a high intake of antioxidants, as a consequence of high consumption of fruit and vegetables, may lower the risk not only for gastric cancer of the intestinal type, but also for diffuse type adenocarcinoma and cardia cancer.

Topics: Adenocarcinoma; Adult; Aged; Antioxidants; Ascorbic Acid; beta Carotene; Cardia; Case-Control Studies; Female; Fruit; Helicobacter pylori; Humans; Intestinal Neoplasms; Male; Middle Aged; Odds Ratio; Risk Factors; Smoking; Stomach Neoplasms; Sweden; Vegetables; Vitamin E

Antioxidant vitamins have attracted considerable attention in previous studies of esophageal squamous-cell carcinoma, but dietary studies of adenocarcinoma of the esophagus and gastric cardia remain sparse. Treating these tumors as distinct diseases, we studied intakes of vitamin C, beta-carotene and alpha-tocopherol in a nationwide population-based case-control study in Sweden, with 185, 165, and 258 cases of esophageal adenocarcinoma, esophageal squamous-cell carcinoma, and gastric cardia adenocarcinoma, respectively, and 815 controls. Subjects with a high parallel intake of vitamin C, beta-carotene, and alpha-tocopherol showed a 40-50% decreased risk of both histological types of esophageal cancer compared with subjects with a low parallel intake. Antioxidant intake was not associated with the risk of gastric cardia adenocarcinoma. Separately, vitamin C and beta-carotene reduced the risk of esophageal cancers more than alpha-tocopherol. We found that antioxidant intake is associated with similar risk reductions for both main histological types of esophageal cancer. Our findings indicate that antioxidants do not explain the diverging incidence rates of the 2 histological types of esophageal cancer. Moreover, our data suggest that inverse associations with esophageal squamous-cell carcinoma and adenocarcinoma may be stronger among subjects under presumed higher oxidative stress due to smoking or gastroesophageal reflux, respectively. Our results may be relevant for the implementation of focused, cost-effective preventive measures.

Topics: Adenocarcinoma; Aged; Antioxidants; Ascorbic Acid; beta Carotene; Carcinoma, Squamous Cell; Cardia; Case-Control Studies; Diet; Dietary Supplements; Drug Synergism; Esophageal Neoplasms; Female; Gastroesophageal Reflux; Humans; Male; Multivariate Analysis; Oxidative Stress; Risk Factors; Smoking; Stomach Neoplasms; Sweden; Vitamin E

In order to examine the relationship between dietary iron intake and risk of rectal cancer, a case-control study was carried out in Montevideo, Uruguay. In the time period 1994-1998, 216 newly diagnosed and microscopically verified cases of adenocarcinoma and 433 controls hospitalized for diseases not related with long-term changes in diet were enrolled in the study. Controls were frequency matched to cases on age, sex, residence and urban/rural status. Both series of patients were interviewed face-to-face in the four major hospitals in Montevideo by two trained social workers. Dietary iron was associated with significant increases in risk in men, women, and in both sexes together [odds ratio (OR) 3.2, 95% confidence interval (CI) 1.9-5.3 for the highest tertile of consumption versus the lowest one]. Since meat and its major macronutrients were potential confounders, iron intake was adjusted for these variables without major changes in the results. Furthermore, dietary iron and total fat combined its effects according to a multiplicative model (OR 3.3, 95% CI 1.8-5.8). Finally, an interaction between dietary iron and vitamin C was found. According to the results, iron displayed a significant increase in risk at low levels of vitamin C intake (OR 4.9, 95% CI 2.3-10.5). These results, together with the existing epidemiological and experimental evidence, suggest that dietary iron could play an important role in rectal carcinogenesis.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Ascorbic Acid; Case-Control Studies; Female; Humans; Iron, Dietary; Male; Middle Aged; Rectal Neoplasms; Risk Assessment; Uruguay

Reactive oxygen species (ROS), represented by superoxide, hydrogen peroxide and hydroxyl radicals, have been implicated in many diseases including cancer. ROS have been known to play an important role in the initiation and promotion of multistep carcinogenesis. The cellular antioxidants play a crucial role in protection against neoplastic disease. However, very little is known about the antioxidant defense in cervical carcinoma. This is addressed in the present study. Lipid peroxides, glutathione content and the activities of antioxidant enzymes, together with vitamin C and E content, were estimated in patients who had carcinoma of the cervix, and the values were compared with those of normal women. The results showed a remarkable reduction in the content of glutathione, vitamin E and C. Activities of glutathione peroxidase and superoxide dismutase were also reduced in cervical cancer compared to normal controls (P < 0.001). This reduction was more marked in late stages (III, IV) than in early stages (I, II) (P < 0.001). Glutathione was reduced more in poorly differentiated tumors (grade III) than in well and moderately differentiated ones (grade I, II) (P < 0.05). Levels of lipid peroxides were found to be significantly higher in malignant than in normal tissue samples and their levels were correlated with advanced clinical stage (P < 0.001). Our results suggest impaired antioxidant status in carcinoma of the cervix. This impairment is related to tumor progression.

Topics: Adenocarcinoma; Antioxidants; Ascorbic Acid; Carcinoma, Squamous Cell; Female; Glutathione; Glutathione Peroxidase; Humans; Lipid Peroxidation; Lipid Peroxides; Superoxide Dismutase; Uterine Cervical Neoplasms; Vitamin E

Topics: Adenocarcinoma; Ascorbic Acid; Ascorbic Acid Deficiency; Gingivitis; Humans; Lung Neoplasms; Male; Middle Aged; Polycythemia Vera; Scurvy

The effects of a synthetic phenolic antioxidant, 1-O-hexyl-2,3,5-trimethylhydroquinone (HTHQ), two novel synthetic ascorbic acid derivatives, 3-O-ethyl ascorbic acid (EAsA) and 3-O-dodecylcarbomethylascorbic acid (DAsA), and phenylethyl isothiocyanate (PEITC) on 7,12-dimethylbenz[a]anthracene (DMBA)-induced mammary carcinogenesis were examined in female Sprague-Dawley rats. Groups of 20, 7 week-old rats received an intra-gastric dose (50 mg/kg, b.w.) of DMBA, and starting one week thereafter received powdered diet containing 1.0% HTHQ, 1.0% EAsA, 1.0% DAsA, 0.1% PEITC or a basal diet alone for 35 weeks. Although the final incidences of mammary adenocarcinomas did not significantly differ among the DMBA-treated groups, multiplicities were significantly lowered in the EAsA (1.6+/-1.6 per rat, P < 0.01) and HTHQ (2.6+/-1.9, P < 0.05) animals as compared with the basal diet case (4.1+/-2.9). The average carcinoma volumes were also significantly smaller in rats given EAsA (2.1+/-3.8 cm3, P < 0.05), DAsA (2.5+/-5.3, P < 0.05) or PEITC (2.4+/-5.9, P < 0.05) than in those receiving DMBA alone (4.9+/-9.2). The results indicate that HTHQ, EAsA and PEITC all exert chemopreventive influence on the promotion/progression stage of DMBA-induced rat mammary carcinogenesis, with EAsA being particularly effective. To our knowledge this is the first documented example of an ascorbic acid derivative possessing chemopreventive potential against mammary cancer in vivo.

Topics: 9,10-Dimethyl-1,2-benzanthracene; Adenocarcinoma; Animals; Anticarcinogenic Agents; Antioxidants; Ascorbic Acid; Carcinogens; Cell Transformation, Neoplastic; Chemoprevention; Diet; Female; Hydroquinones; Isothiocyanates; Mammary Neoplasms, Experimental; Rats; Rats, Sprague-Dawley

Scanning and transmission electron microscopy and fluorescence light microscopy were employed to characterize the cytotoxic effects of vitamin C (VitC), vitamin K3 (VitK3) or a VitC:VK3 combination on a human bladder carcinoma cell line (T24) following 1-h and 2-h vitamin treatment. T24 cells exposed to VitC alone exhibited membranous damage (blebs and endoplasmic extrusions, elongated microvilli). VitK3-treated cells displayed greater membrane damage and enucleation than those treated with VitC as well as cytoplasmic defects characteristic of cytoskeletal damage. VitC:VitK3-treated cells showed exaggerated membrane damage and an enucleation process in which the perikarya separate from the main cytoplasmic cell body by self-excision. Self-excisions continued for perikarya which contained an intact nucleus surrounded by damaged organelles. After further excisions of cytoplasm, the nuclei exhibited nucleolar segregation and chromatin decondensation followed by nuclear karryorhexis and karyolysis. This process of cell death induced by oxidative stress was named autoschizis because it showed both apoptotic and necrotic morphologic characteristics.

Topics: Adenocarcinoma; Antineoplastic Agents; Ascorbic Acid; Cell Death; Drug Screening Assays, Antitumor; Drug Synergism; Humans; Microscopy, Electron, Scanning; Time Factors; Tumor Cells, Cultured; Urinary Bladder Neoplasms; Vitamin K; Vitamin K 3

The present study has examined the role of life-style on plasma and erythrocyte membrane lipid profile in 25 adult male gastric cancer patients as well as age and sex-matched controls. Total, free and LDH cholesterol were markedly elevated in plasma and erythrocyte membrane whereas HDL cholesterol and triglycerides were significantly reduced in gastric cancer patients. These changes can be attributed to alcohol consumption and cigarette smoking-risk factors in gastric carcinogenesis, associated with low levels of ascorbic acid and vitamin E.

Topics: Adenocarcinoma; Ascorbic Acid; Cholesterol; Cholesterol, LDL; Erythrocyte Membrane; Humans; Life Style; Lipids; Male; Middle Aged; Phospholipids; Stomach Neoplasms; Triglycerides; Vitamin E

The effects of vitamins E and E, beta-carotene and selenium on development of N-nitrosobis(2-oxopropyl)amine (BOP)-induced pancreatic tumours in hamsters were investigated. Dietary supplementation of vitamin C, alone as well as in combination with beta-carotene resulted in consistently lower numbers of advanced ductular lesions. The differences with the controls, however, did not reach the level of statistical significance. Beta-Carotene alone demonstrated no inhibitory effect on the development of (pre)neoplastic lesions in the pancreas. Vitamin E or Se, either alone or in combination, had no effect on the development of advanced ductular lesions in BOP-treated hamsters.

Topics: Adenocarcinoma; Animals; Ascorbic Acid; beta Carotene; Body Weight; Carcinogens; Carcinoma, Ductal, Breast; Carotenoids; Cricetinae; Diet; Male; Mesocricetus; Nitrosamines; Organ Size; Pancreatic Neoplasms; Selenium; Vitamin E

Topics: Acute Disease; Acute Kidney Injury; Adenocarcinoma; Anuria; Ascorbic Acid; Humans; Infusions, Intravenous; Kidney Calculi; Male; Middle Aged; Oxalates; Prostatic Neoplasms

Selenium has been suggested to be anticarcinogenic and to play a role in the cellular defense against oxidative stress. The association between toenail selenium (a marker of long-term selenium status) and lung cancer was investigated in a cohort study of diet and cancer that started in 1986 among 120,852 Dutch men and women aged 55-69 years. After 3.3 years of follow-up, 550 incident cases of lung carcinoma were detected. Toenail selenium data were available for 370 lung cancer cases and 2459 members of a randomly selected subcohort. The rate ratio of lung cancer for subjects in the highest compared to the lowest quintile of toenail selenium, after controlling for age, gender, smoking, and education, was 0.50 (95% confidence interval, 0.30-0.81), with a significant inverse trend across quintiles (P = 0.006). The protective effect of selenium was concentrated in subjects with a relatively low dietary intake of beta-carotene or vitamin C. The rate ratio in the highest compared to the lowest quintile of selenium was 0.45 in the low beta-carotene group (95% confidence interval, 0.22-0.92; trend P = 0.028) and 0.36 in the low vitamin C group (95% confidence interval, 0.17-0.75; trend P < 0.001). The results of this study support an inverse association between selenium status and lung cancer and suggest a modification of the effect of selenium by the antioxidants beta-carotene and vitamin C.

Topics: Adenocarcinoma; Age Factors; Aged; Ascorbic Acid; beta Carotene; Carcinoma; Carcinoma, Small Cell; Carcinoma, Squamous Cell; Carotenoids; Cohort Studies; Education; Feeding Behavior; Female; Follow-Up Studies; Humans; Incidence; Lung Neoplasms; Male; Middle Aged; Nails; Netherlands; Prospective Studies; Risk Factors; Selenium; Sex Factors; Smoking; Surveys and Questionnaires; Time Factors; Toes; Vitamin A

Six synthetic 2,6-dimethoxyhydroquinone derivatives were shown to have different degrees of cytotoxicity to two human tumor cell lines (KB and PC-9) under the synergistic activation of L-ascorbic acid. Two representative compounds displayed very low time-schedule-independent index, showing that the cytotoxic action is independent of time of drug treatment. The addition of catalase produced a significant inhibitory effect on the cytotoxicity of two representative compounds, indicating that the cytotoxic action is mediated by the generation of H2O2, which may yield hydroxyl radicals via various mechanisms. ESR studies employing the spin-trap 5,5-dimethyl-1-pyrroline-N-oxide (DMPO) showed that massive hydroxyl radicals were generated from four of these drugs as a non-linear function of L-ascorbic acid concentration. The results indicate the possible involvement of hydroxyl radicals in the cytotoxic action of these novel drugs.

Topics: Adenocarcinoma; Aminacrine; Antineoplastic Agents; Ascorbic Acid; Carcinoma, Squamous Cell; Catalase; Drug Interactions; Electron Spin Resonance Spectroscopy; Humans; Hydroquinones; Hydroxides; Hydroxyl Radical; Lung Neoplasms; Mouth Neoplasms; Time Factors; Tumor Cells, Cultured

In 1975, we reported the remarkable case of a 42-year-old man with histologically proven widely disseminated reticulum cell sarcoma who, in a remarkably short time, appeared to enjoy not one, but two, complete spontaneous regressions of his fatal illness. Both these regressions coincided exactly in time with intravenous high-dose ascorbate administration, and it seemed reasonable to conclude that this unconventional therapy must have been responsible for his excellent responses. For those interested in spontaneous regressions of cancer and the possible mechanisms, we now report his subsequent progress some 17 years later.

Topics: Adenocarcinoma; Ascorbic Acid; Dose-Response Relationship, Drug; Humans; Lymphoma, Non-Hodgkin; Middle Aged; Neoplasm Regression, Spontaneous; Thyroid Neoplasms

The chemopreventive actions of sodium selenite (SS), magnesium chloride (MC), ascorbic acid (AA) and retinyl acetate (RA), given singly or in combinations, on mammary carcinogenesis induced by 30 mg of 7,12-dimethylbenz[a]anthracene (DMBA) in female adult rats were evaluated. Administration of modulators was carried out from the age of 40 +/- 3 days to 240 +/- 3 days. When DMBA alone was given 100% of the rats developed mammary tumors. When modulators were given singly the tumor incidences were reduced to 51.77% (SS), 46.4% (MC), 57.1% (AA) and 48.1% (RA). When the modulators were given in combination of twos, the tumor incidences were further reduced to 29.5% (SS + MC), 31% (SS + AA), 29.6% (SS + RA), 25.9% (MC + AA), 31.8% (MC + RA) and 34.6% (AA + RA). Administration of modulators in combinations of threes resulted in still further reduction of tumor incidences to 22.2% (SS + MC + AA), 19.2% (SS + MC + RA), 16% (MC + AA + RA) and 23.1% (AA + RA + SS). When all four modulators were given concurrently the tumor incidence was only 12%. Further, the number of tumors per tumor-bearing animal declined with the increase in the number of agents used in combination for modulation.

Topics: 9,10-Dimethyl-1,2-benzanthracene; Adenocarcinoma; Adenofibroma; Animals; Antineoplastic Combined Chemotherapy Protocols; Ascorbic Acid; Body Weight; Diterpenes; Drug Administration Schedule; Female; Magnesium Chloride; Mammary Neoplasms, Experimental; Rats; Retinyl Esters; Selenic Acid; Selenium; Selenium Compounds; Vitamin A

Topics: Adenocarcinoma; Ascorbic Acid; Colonic Neoplasms; Colonic Polyps; Diet; Dietary Fiber; Risk Factors; Triticum; Vitamin E

The effects of sodium ascorbate (vitamin C) and 2-methyl-1,4-naphthoquinone (vitamin K3) administered separately or in combination on the in vitro cultured human neoplastic cell lines MCF-7 (breast carcinoma), KB (oral epidermoid carcinoma), and AN3-CA (endometrial adenocarcinoma) have been examined. When given separately, vitamin C or K3 had a growth inhibiting action only at high concentrations (5.10(3) mumol/1 and 10(5) nmol/l, respectively). Combined administration of both vitamins demonstrated a synergistic inhibition of cell growth at 10 to 50 times lower concentrations. At this level separately given vitamins are not toxic. The sensitivity to this treatment was somewhat different in the three cell lines, being slightly higher for KB line. This tumor cell growth inhibitory effect was completely suppressed by the addition of catalase to the culture medium containing vitamins C and K3, suggesting an excessive production of hydrogen peroxide as being implied in mechanisms responsible for the above-mentioned effects.

Topics: Adenocarcinoma; Ascorbic Acid; Breast Neoplasms; Carcinoma, Squamous Cell; Catalase; Cell Division; Drug Synergism; Female; Humans; Mouth Neoplasms; Tumor Cells, Cultured; Uterine Neoplasms; Vitamin K

Topics: Adenocarcinoma; Adult; Aged; Ascorbic Acid; Cell Migration Inhibition; Female; Humans; Leukocyte Adherence Inhibition Test; Leukocytes; Middle Aged; Ovarian Neoplasms; Rosette Formation; Vitamin A

This long-term study deals with the effect of ascorbic acid on chemically induced carcinogenesis of the small intestine in rats. Carcinoma was induced in 27 animals by application of N-Ethyl-N'-nitro-N-nitrosoguanidine (ENNG) alone in the drinking water (120 mg/1). The average survival time was 238 ( 40) days. The addition of large amounts of ascorbic acid to the food (3 g/100 g food) did not suppress the development of tumors. On the contrary, a significant reduction in the survival time was seen. All animals receiving ENNG and ascorbic acid only lived 207 ( 45) days on average. Neither histological type of tumor spread was influenced by the use of ascorbic acid. Giving ascorbic acid alone had no effect on the survival time and did not lead to changes in the tissue of the small intestine.

Topics: Adenocarcinoma; Animals; Ascorbic Acid; Carcinogens; Digestive System; Gastrointestinal Neoplasms; Intestinal Polyps; Long-Term Care; Male; Methylnitronitrosoguanidine; Rats; Rats, Inbred Strains

A case-control study was conducted based on 427 white males with lung cancer of the squamous, small cell, and adenocarcinoma histologic subtypes and 1,094 white male controls admitted to Roswell Park Memorial Institute between the years 1957 and 1965. The relation between selected dietary factors and lung cancer risk was examined for each histologic subtype while controlling for past cigarette use. Dietary vitamin A was found to be negatively associated with risk for squamous cell and small cell carcinoma, but not for adenocarcinoma of the lung. No significant association was observed, however, between dietary vitamin C, fats, or fiber and any of the lung cancer subtypes. These results suggest that the apparent protective effect of vitamin A in lung cancer may be histologic type-specific.

Topics: Adenocarcinoma; Adult; Aged; Alcohol Drinking; Ascorbic Acid; Carcinoma, Small Cell; Carcinoma, Squamous Cell; Diet; Dietary Fats; Dietary Fiber; Humans; Lung Neoplasms; Male; Middle Aged; Risk; Smoking; Vitamin A

Topics: Adenocarcinoma; Adult; Aged; Ascorbic Acid; Carcinoma; Combined Modality Therapy; Female; Fluorouracil; Gastrectomy; Humans; Male; Middle Aged; Neoplasm Metastasis; Postoperative Care; Stomach Neoplasms

Levels of certain metabolites of peroxidation of lipids such as diene conjugates malonic dialdehyde, ascorbic acid, dehydroascorbic acid and diketogulonic acid were compared in 39 cases of gastric ulcer, 25 patients with gastric cancer and 14 healthy subjects. Diene conjugates and malonic dialdehyde levels appeared to be increased in cases of gastric ulcer and cancer. This was matched by a decrease in ascorbic acid and dehydroascorbic acid levels. Ulcer patients revealed enhanced diketogulonic acid concentration.

Topics: 2,3-Diketogulonic Acid; Adenocarcinoma; Aged; Ascorbic Acid; Dehydroascorbic Acid; Female; Humans; Lipid Peroxides; Male; Malondialdehyde; Middle Aged; Stomach Neoplasms; Stomach Ulcer

Human large bowel neoplasia seems to be caused by environmental carcinogens. The experimental carcinogen, 1,2-dimethylhydrazine (DMH), must be oxidized in the body to have effect. The antioxidants, butylated hydroxyanisole (BHA) and ascorbic acid, were tested for efficacy in prevention of experimental large bowel neoplasia. Carcinogenesis was induced in female CF-1 mice by administering DMH, 20 mg/kg, sq for 24 weekly doses. Test animals received varying doses of ascorbic acid, BHA, or both agents together. Animals were sacrificed when moribund or at 35 weeks. All colons were totally embedded and analyzed histologically. Ascorbic acid demonstrated no effects on incidence or density of large bowel tumors. Ascorbic acid did increase the ratio of adenomas to adenocarcinomas. BHA decreased the incidence and density of large bowel tumors. The lowest incidence was obtained in the group receiving both agents combined. It is concluded that BHA is effective in the chemoprevention of DMH-induced large bowel neoplasms. Ascorbic acid demonstrates only modest effect. The greatest effect on tumor incidence is seen when ascorbic acid and BHA are administered together.

Topics: 1,2-Dimethylhydrazine; Adenocarcinoma; Adenoma; Administration, Oral; Animals; Anisoles; Ascorbic Acid; Butylated Hydroxyanisole; Colonic Neoplasms; Diet; Dimethylhydrazines; Female; Mice

Topics: Adenocarcinoma; Adenoma; Animals; Ascorbic Acid; Carcinogens; Humans; Neoplasms; Neoplasms, Experimental; Nitrosamines; Orthomolecular Therapy; Palliative Care; Rats

Topics: Adenocarcinoma; Animals; Antioxidants; Ascorbic Acid; Carcinoma, Squamous Cell; Male; Methylnitronitrosoguanidine; Neoplasms; Rats; Rats, Inbred F344; Sarcoma; Stomach Neoplasms

Decreased tumor incidence, increased latent period, and increased survival time were observed in C3H/HeJ mice fed supplemental beta-carotene for 3 days and then inoculated with 10(4) C3HBA (syngeneic) tumor cells. In addition, C3H/HeJ, C3H/He, and CBA/J mice, fed supplemental beta-carotene beginning immediately after they were inoculated with 2 X 10(5) C3HBA tumor cells, showed decreased tumor growth and increased survival time. When beta-carotene was fed to mice in which palpable tumors were already present, it similarly slowed tumor growth and extended animal survival time. Ascorbic acid supplementation (5 g/kg diet), introduced into the experiment as a possible synergist for beta-carotene's antitumor action, was without therapeutic action when tested in the presence or absence of beta-carotene supplements. The basal diet, a standard commercial mouse chow, contains more vitamin A than the National Research Council's recommended dietary allowance for normal rodents and supports normal growth, reproduction, and longevity of normal mice. The work reported here is the first demonstration of the antitumor action of beta-carotene in animals with a transplanted tumor.

Topics: Adenocarcinoma; Animals; Ascorbic Acid; Bone and Bones; Carotenoids; Diet; Female; Male; Mice; Mice, Inbred C3H; Mice, Inbred CBA; Neoplasm Transplantation; Vitamin A

A systematic study of vitamin C blood levels in patients with cancer and an evaluation of their modifications when the patients were orally treated with daily large doses of ascorbic acid (5g/day) have been carried out. For excluding any interference on intestinal vitamin C absorption, all patients with digestive tract cancer have been excluded. Our first results concern 24 lung cancer and 35 bladder cancer patients, operable or not, of different sex and age. The study has shown hypovitaminosis C subclinic conditions for the greater part of subjects: in fact the average haematic rate of ascorbic acid approaches to lower level of physiologic range, appearing very low particularly for the younger patients. Periodic haematic dosages of vitamin C of unoperable and operated patients treated with large doses of ascorbic acid, have shown a rapid increase of its blood concentration which frequently has been very over 1500 micrograms%, the higher level of normal range. These high vitamin haematic levels, generally constant during the time, appear usefull in increasing the defence reactions of the cancerous patient.

Topics: Adenocarcinoma; Adult; Age Factors; Aged; Ascorbic Acid; Ascorbic Acid Deficiency; Carcinoma; Carcinoma, Squamous Cell; Female; Humans; Lung Neoplasms; Male; Middle Aged; Neoplasms; Urinary Bladder Neoplasms

This study applies to the agency of vitamin C on chemical carcinogenesis in the small intestine of rats. Administration of N-Ethyl-N'-nitro-N-nitrosoguanidine (ENNG) in drinking water produced tumors of the small intestine after 18 weeks in more than 90%. The induction of tumors could not be suppressed by a large amount (2-3%) of sodium ascorbate in food, but the depth of tumor infiltration was restricted. Cancer developed in 29 of 36 rats receiving ENNG only. In 25 animals of this group growth of tumor corresponded to a P4 stage. In 24 of 35 animals, additionally receiving vitamin C, P4 stage was observed in only 13 cases. Pathological changes in the small intestine could not be observed after the sole administration of vitamin C.

Topics: Adenocarcinoma; Animals; Ascorbic Acid; Dose-Response Relationship, Drug; Duodenal Neoplasms; Duodenum; Male; Methylnitronitrosoguanidine; Neoplasms, Experimental; Rats; Rats, Inbred Strains

Topics: Adenocarcinoma; Animals; Ascorbic Acid; Biotransformation; Diet; Fish Products; Male; Mutagens; Neoplasms, Experimental; Nitrites; Rats; Salmonella typhimurium; Stomach Neoplasms

Topics: Adenocarcinoma; Animals; Ascorbic Acid; Calcium; Drug Therapy, Combination; Immunity, Cellular; Lymphocytes; Magnesium; Mammary Neoplasms, Experimental; Mice; Mice, Inbred C3H

Topics: Adenocarcinoma; Adult; Aged; Ascorbic Acid; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Humans; Middle Aged; Skin Neoplasms

Massive doses of vitamin C protected rats against liver tumour production by aminopyrine and sodium nitrite, but the protection against lung and kidney tumour production was not complete. The mechanism is in part due to blockage of in vivo nitrosation. Other unknown factors may operate to give the liver complete protection.

Topics: Adenocarcinoma; Aminopyrine; Animals; Ascorbic Acid; Liver Neoplasms; Male; Neoplasms, Experimental; Nitrites; Rats

Topics: Adenocarcinoma; Aged; Animals; Ascorbic Acid; Barium Sulfate; Cardia; Diet; Esophageal Neoplasms; Esophagogastric Junction; Female; Gastrectomy; Hematemesis; Humans; Jejunum; Male; Methods; Middle Aged; Milk; Physical Exertion; Physical Therapy Modalities; Radiography

Topics: Adenocarcinoma; Ascorbic Acid; Bone Neoplasms; Breast Neoplasms; Humans; Neoplasm Metastasis

Topics: Adenocarcinoma; Animals; Ascorbic Acid; Female; Gammaretrovirus; Golgi Apparatus; Histocytochemistry; Mammary Glands, Animal; Mammary Neoplasms, Experimental; Mice

Topics: Adenocarcinoma; Aged; Angiography; Ascorbic Acid; Humans; Hypertension, Renal; Indium; Iron; Kidney Diseases, Cystic; Kidney Neoplasms; Male; Middle Aged; Pentetic Acid; Photography; Radioisotopes; Technetium

Topics: Adenocarcinoma; Aged; Animals; Ascorbic Acid; Biological Assay; Breast Neoplasms; Child; Child, Preschool; Female; Humans; Hypophysectomy; Luteinizing Hormone; Male; Ovary; Rats

Topics: Adenocarcinoma; Ascorbic Acid; Humans; Osteitis Deformans; Vitamins