beta-carotene and Mesothelioma

Uncertainty remains over whether or not high intakes of retinol or vitamin A consumed through food or supplements may increase fracture risk. This intervention study found no increase in fracture risk among 2,322 adults who took a controlled, high-dose retinol supplement (25,000 IU retinyl palmitate/day) for as long as 16 years. There was some evidence that beta-carotene supplementation decreased fracture risk in men.. There is conflicting epidemiological evidence regarding high intakes of dietary or supplemental retinol and an increased risk for bone fracture. We examined fracture risk in a study administering high doses of retinol and beta-carotene (BC) between 1990 and 2007.. The Vitamin A Program was designed to test the efficacy of retinol and BC supplements in preventing malignancies in persons previously exposed to blue asbestos. Participants were initially randomised to 7.5 mg retinol equivalents (RE)/day as retinyl palmitate, 30 mg/day BC or 0.75 mg/day BC from 1990 to 1996; after which, all participants received 7.5 mg RE/day. Fractures were identified by questionnaire and hospital admission data up until 2006. Risk of any fracture or osteoporotic fracture according to cumulative dose of retinol and BC supplementation was examined using conditional logistic regression models adjusting for age, sex, smoking, body mass index, medication use and previous fracture.. Supplementation periods ranged from 1 to 16 years. Of the 2,322 (664 females and 1,658 males) participants, 187 experienced 237 fractures. No associations were observed between cumulative dose of retinol and risk for any fracture (OR per 10 g RE=0.83; 95% CI, 0.63-1.08) or osteoporotic fracture (OR per 10 g RE=0.95; 95% CI 0.64-1.40). Among men, cumulative dose of BC was associated with a slightly reduced risk of any fracture (OR per 10 g=0.89; 95% CI 0.81-0.98) and osteoporotic fracture (OR per 10 g=0.84; 95% CI 0.72-0.97).. This study observed no increases in fracture risk after long-term supplementation with high doses of retinol and/or beta-carotene.

Topics: Adult; Aged; beta Carotene; Dietary Supplements; Diterpenes; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Follow-Up Studies; Humans; Incidence; Lung Neoplasms; Male; Mesothelioma; Middle Aged; Occupational Diseases; Osteoporotic Fractures; Retinyl Esters; Risk Assessment; Vitamin A; Western Australia

Former blue asbestos workers known to be at high risk of asbestos-related diseases, particularly malignant mesothelioma and lung cancer, were enrolled in a chemo-prevention program using vitamin A. Our aims were to compare rates of disease and death in subjects randomly assigned to beta-carotene or retinol. Subjects were assigned randomly to take 30 mg/day beta-carotene (512 subjects) or 25,000 IU/day retinol (512 subjects) and followed up through death and cancer registries from the start of the study in June 1990 till May 1995. Comparison between groups was by Cox regression in both intention-to-treat analyses and efficacy analyses based on treatment actually taken. Median follow-up time was 232 weeks. Four cases of lung cancer and 3 cases of mesothelioma were observed in subjects randomised to retinol and 6 cases of lung cancer and 12 cases of mesothelioma in subjects randomised to beta-carotene. The relative rate of mesothelioma (the most common single cause of death in our study) for those on retinol compared with those on beta-carotene was 0.24 (95% CI 0.07-0.86). In the retinol group, there was also a significantly lower rate for death from all causes but a higher rate of ischaemic heart disease mortality. Similar results were found with efficacy analyses. Our results confirm other findings of a lack of any benefit from administration of large doses of synthetic beta-carotene. The finding of significantly lower rates of mesothelioma among subjects assigned to retinol requires further investigation.

Topics: Adult; Aged; Aged, 80 and over; Anticarcinogenic Agents; Asbestos, Crocidolite; beta Carotene; Female; Humans; Incidence; Lung Neoplasms; Male; Mesothelioma; Middle Aged; Myocardial Ischemia; Occupational Exposure; Patient Compliance; Risk Factors; Smoking; Vitamin A

High blood levels of β-carotene and increased intake in the diets are inversely proportional to incidence of many cancer types. Antioxidant activity of β-carotene was proposed to be related with its antitumor effect. Despite this plant derivative substance being sought in many cancer types, the effectiveness of β-carotene against malignant mesothelioma remained unclear. Therefore, the present study aims to explore the impact of β-carotene on cell viability, apoptosis, and oxidative stress in mesothelioma cells. Human mesothelioma cell SPC212 were treated with β-carotene (3.125-200 μM) for 24, 48, 72, and 96 h. Cytotoxicity was measured with the MTT assay (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide). Annexin-V/propidium iodide (PI) and caspase 3/7 biomarkers were used to identify apoptotic cells. Finally, the oxidative stress was evaluated with flow cytometry. The results of the measurements indicated a significant decline in viable mesothelioma cancer cell numbers upon β-carotene treatment in time- and concentration-dependent manner when compared to control cells. Furthermore, β-carotene treatment led to apoptosis induction according to both annexin V/PI and caspase 3/7 assays. Furthermore, β-carotene increased oxidative stress in SPC212 cells. These results show how β-carotene affects proliferative, apoptotic, and oxidative properties in SPC212 malignant pleural mesothelioma cells and provide useful insights into future studies.

Topics: Apoptosis; beta Carotene; Cell Count; Cell Line, Tumor; Humans; Mesothelioma; Mesothelioma, Malignant

The aim of this study was to investigate the possible relationship between antioxidant vitamin levels and malignant pleural mesothelioma (MPM). For this purpose, we measured the serum levels of 4 antioxidant vitamins, β-carotene, α-tocopherol, retinol, and ascorbic acid, in patients with environmentally induced MPM and in healthy controls from one tremolite village (Kureysler), the biggest erionite village (Tuzkoy) and Ankara. A total of 160 subjects were enrolled in the study, 42 (26.3%) diagnosed with MPM and 118 (73.7%) healthy subjects. A comparison was made between the MPM group and three control groups of which two were exposed and one was unexposed to mineral fibers. The study population consisted of 82 males (51%) and 78 females (49%) with a mean of age of 44.8±14 years (range; 20-65 years). Lowest levels of β-carotene, ascorbic acid, and α-tocopherol were found in MPM patients (MPM vs control groups combined, p<0.0001 for each antioxidant vitamin), without any relation to age or sex. There was no significant difference between the antioxidant levels of healthy controls of Tuzkoy and Ankara. In conclusion; our findings suggested an increased risk of MPM being associated with low levels of α-tocopherol and ascorbic acid in patients with MPM.

Topics: Adult; alpha-Tocopherol; Antioxidants; Ascorbic Acid; beta Carotene; Case-Control Studies; Female; Humans; Male; Mesothelioma; Middle Aged; Pleural Neoplasms; Risk; Vitamin A

Malignant mesothelioma is an aggressive tumor, usually induced by asbestos exposure, that has a poor prognosis and is unresponsive to conventional therapy. The present study was aimed at assessing the potential for interferon-alpha (IFN-alpha)-based therapies in a murine model for malignant mesothelioma. The effect of recombinant human IFN-alpha B/D on tumor growth, alone and in combination with either of two immunomodulatory and antiproliferative agents beta-carotene or alpha-difluoromethylornithine (DFMO), was assessed. The data suggest that IFN-alpha treatment is most efficacious when commenced early in tumor development. Combination of IFN-alpha with either DFMO or dietary beta-carotene supplementation improved the effect of an otherwise suboptimal IFN-alpha therapy regimen. Both IFN-alpha and beta-carotene had in vivo stimulatory effects on immune cells, perhaps indirectly by inhibiting TGF-beta generation. The immunomodulatory effects may contribute, at least in part, to the positive antitumor and clinical activities of the treatments in this model.

Topics: Adjuvants, Immunologic; Animals; Antineoplastic Combined Chemotherapy Protocols; beta Carotene; Carotenoids; Eflornithine; Female; Interferon Type I; Lymphocytes, Tumor-Infiltrating; Macrophages; Mesothelioma; Mice; Mice, Inbred CBA; Mice, Inbred Strains; Recombinant Proteins; RNA, Messenger; Transforming Growth Factor beta; Tumor Cells, Cultured

In the first part of this study we have shown how the serum levels of four selected tumour markers, namely tissue polypeptide antigen (TPA), carcino-embryonic antigen (CEA), hyaluronic acid (HA) and ferritin, display patterns characteristic of mesothelioma (M) or bronchogenic carcinoma (BC) in asbestos-exposed workers, and we hypothesize that the differences in marker patterns correspond to differences in carcinogenesis mechanisms. In a preliminary study, we found these specific marker patterns in 5/19 exposed workers of whom only one demonstrated any radiological signs of disease. Thus these specific marker patterns may be early events, occurring long (possibly years) before the classical radiological signs of exposure to asbestos. Accordingly they afford an optimal opportunity for prevention which should be adapted to the carcinogenesis mechanism as it is revealed by the marker pattern; it is aimed at antagonizing free radical carcinogenesis in all persons with TPA levels in excess of 100 U/l or Ferritin in excess of 400 ng/ml, and at inhibiting chemical carcinogenesis in those having elevated CEA levels (over 3 ng/ml). The mechanisms involved in these inhibitory processes are described and discussed, as well as the practical implementations that proceed from them. A prevention trial is now being started among 300 active and retired workers of an asbestos-cement works in northern France; the design of the study is presented. This prevention programme should be maintained over many years and holds a strong potential for reducing the untoward effects of exposure to asbestos.

Topics: Acetylcysteine; Antigens, Neoplasm; Asbestos; Ascorbic Acid; beta Carotene; Biomarkers, Tumor; Carcinoembryonic Antigen; Carcinoma, Bronchogenic; Carotenoids; Cohort Studies; Ferritins; Humans; Hyaluronic Acid; Longitudinal Studies; Lung Neoplasms; Male; Mesothelioma; Middle Aged; Occupational Diseases; Occupational Exposure; Peptides; Riboflavin; Selenium; Tissue Polypeptide Antigen; Vitamin A; Vitamin E