beta-carotene and Carcinoma--Squamous-Cell

'Keratinocyte cancer' is now the preferred term for the most commonly identified skin cancers basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (cSCC), which were previously commonly categorised as non-melanoma skin cancers (NMSC). Keratinocyte cancer (KC) represents about 95% of malignant skin tumours. Lifestyle changes have led to increased exposure to the sun, which has, in turn, led to a significant increase of new cases of KC, with a worldwide annual incidence of between 3% and 8%. The successful use of preventive measures could mean a significant reduction in the resources used by health systems, compared with the high cost of the treatment of these conditions. At present, there is no information about the quality of the evidence for the use of these sun protection strategies with an assessment of their benefits and risks.. To assess the effects of sun protection strategies (i.e. sunscreen and barrier methods) for preventing keratinocyte cancer (that is, basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (cSCC) of the skin) in the general population.. We searched the following databases up to May 2016: the Cochrane Skin Group Specialised Register, CENTRAL, MEDLINE, Embase, and LILACS. We also searched five trial registries and the bibliographies of included studies for further references to relevant trials.. We included randomised controlled clinical trials (RCTs) of preventive strategies for keratinocyte cancer, such as physical barriers and sunscreens, in the general population (children and adults), which may provide information about benefits and adverse events related to the use of solar protection measures. We did not include trials focused on educational strategies to prevent KC or preventive strategies in high-risk groups. Our prespecified primary outcomes were BCC or cSCC confirmed clinically or by histopathology at any follow-up and adverse events.. Two review authors independently selected studies for eligibility using Early Review Organizing Software (EROS). Similarly, two review authors independently used predesigned data collection forms to extract information from the original study reports about the participants, methods of randomisation, blinding, comparisons of interest, number of participants originally randomised by arm, follow-up losses, and outcomes, and they assessed the risk of bias. We resolved any disagreement by consulting a third author and contacted trial investigators of identified trials to obtain additional information. We used standard methodological procedures expected by Cochrane.. We included one RCT (factorial design) that randomised 1621 participants.This study compared the daily application of sunscreen compared with discretionary use of sunscreen, with or without beta-carotene administration, in the general population. The study was undertaken in Australia; 55.2% of participants had fair skin, and they were monitored for 4.5 years for new cases of BCC or cSCC assessed by histopathology. We found this study to be at low risk of bias for domains such as allocation, blinding, and incomplete outcome data. However, we found multiple unclear risks related to other biases, including an unclear assessment of possible interactions between the effects of the different interventions evaluated (that is, sunscreen and beta-carotene). We found no difference in terms of the number of participants developing BCC (n = 1621; risk ratio (RR) 1.03, 95% confidence interval (CI) 0.74 to 1.43) or cSCC (n = 1621; RR 0.88, 95% CI 0.50 to 1.54) when comparing daily application of sunscreen with discretionary use, even when analyses were restricted to groups without beta-carotene supplementation. This evidence was of low quality, which means that there is some certainty that future studies may alter our confidence in this evidence.We reported adverse events in a narrative way and included skin irritation or contact allergy.We identified no studies that evaluated other sun protection measures, such as the use of sun-protective clothing, sunglasses, or hats, or seeking the shade when outdoors.. In this review, we assessed the effect of solar protection in preventing the occurrence of new cases of keratinocyte cancer. We only found one study that was suitable for inclusion. This was a study of sunscreens, so we were unable to assess any other forms of sun protection. The study addressed our prespecified primary outcomes, but not most of our secondary outcomes. We were unable to demonstrate from the available evidence whether sunscreen was effective for the prevention of basal cell carcinoma (BCC) or cutaneous squamous cell carcinoma (cSCC).Our certainty in the evidence was low because there was a lack of histopathological confirmation of BCC or cSCC in a significant percentage of cases. Amongst other sources of bias, it was not clear whether the study authors had assessed any interaction effects between the sunscreen and beta-carotene interventions. We think that further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.

Topics: Adult; Australia; beta Carotene; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Child; Humans; Neoplasms, Radiation-Induced; Randomized Controlled Trials as Topic; Skin Neoplasms; Sunlight; Sunscreening Agents; Ultraviolet Rays; Vitamins

Chemoprevention is one of the cancer prevention methods, applied for the oral squamous cell carcinoma and its main precursor lesions--leukoplakia and erythroplakia. Presently, the most extensive clinically studied group used in such cases are retinoids: vitamin A (retinol), 13-cis-retinic acid (isotretinoin), N-(4-hydroxyphenyl)retinamide (fenretinide) and precursor of vitamin A--beta-carotene. However, despite good short-time effectiveness, retinoids do not prevent recurrences of the lesions and insignificantly increase cancer-free survival. Moreover, they are also characterized by relatively high toxicity. Vitamin E, Bowman-Birkprotease inhibitor, Spirulina fusiformis and green tee extracts as well as traditional Chinese herbs known as ZengShengPing were also found as effective agents. Lack of activity was reported for cyclooxygenase inhibitors--ketorolac and celecoxib. More promising data was collected from animal experimental studies with chemically induced oral squamous cell carcinoma. Chemopreventive activity was revealed for various agents including plant-derived compounds like resveratrol, green and black tee polyphenols, as well as protocatechuic, ellagic and caffeic acids.

Topics: Animals; Antineoplastic Agents; beta Carotene; Carcinoma, Squamous Cell; Chemoprevention; Drugs, Chinese Herbal; Fenretinide; Humans; Isotretinoin; Mouth Neoplasms; Neoplasm Recurrence, Local; Phytotherapy; Precancerous Conditions; Vitamin A

Topics: Anticarcinogenic Agents; Antioxidants; beta Carotene; Carcinoma, Squamous Cell; Cell Transformation, Neoplastic; Chemoprevention; Head and Neck Neoplasms; Humans; Leukoplakia, Oral; Retinoids; Tea

Cervix carcinoma is an important health problem world-wide, being the second most common cancer among women, ranking first in many developing countries. A number of important epidemiological risk factors have been identified as contributing to the development of CIN and invasive cervix carcinoma. Of key importance is infection with human papillomavirus (HPV), which is the primary risk factor. There are evolving primary and secondary preventive strategies that could further reduce the burden from cervical carcinoma. The possible primary preventive strategies include risk reduction, diet or dietary supplements, HPV vaccines, and other chemopreventive agents. The possible advances in secondary preventive strategies include new technologies for Pap smears, HPV typing triage, and other adjuvant screening procedures. The impact of these strategies will depend upon evidence to support their use along with the characteristics of the population and environment in which they are used.

Topics: Anticarcinogenic Agents; Antioxidants; Ascorbic Acid; beta Carotene; Carcinoma, Squamous Cell; Clinical Trials as Topic; Colposcopy; Diet; Female; Folic Acid; Humans; Image Processing, Computer-Assisted; Mass Screening; Nutritional Requirements; Papanicolaou Test; Papillomaviridae; Papillomavirus Infections; Photochemotherapy; Risk Factors; Tumor Virus Infections; Uterine Cervical Dysplasia; Uterine Cervical Neoplasms; Vaginal Smears; Viral Vaccines; Vitamin E; Vitamins

Topics: Antioxidants; beta Carotene; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Combined Modality Therapy; Cryotherapy; Humans; Retinoids; Skin Neoplasms

Second primary cancers often occur in head and neck cancer patients successfully treated by radiation therapy. Experimental and epidemiological data suggest that these second primaries might be prevented by antioxidant vitamins, in particular beta-carotene and alpha-tocopherol. A randomized double-blind clinical trial is being conducted in Canada to determine whether vitamin supplementation with beta-carotene (30 mg/d) and alpha-tocopherol (400 IU/d) reduces the incidence of second primaries in head and neck cancer patients treated by radiation therapy.

Topics: Acetylcysteine; Antineoplastic Agents; Antioxidants; beta Carotene; Carcinoma, Squamous Cell; Carotenoids; Follow-Up Studies; Head and Neck Neoplasms; Humans; Neoplasm Staging; Neoplasms, Second Primary; Risk Factors; Vegetables; Vitamin A; Vitamin E; Vitamins

Topics: Antioxidants; beta Carotene; Carcinoma, Squamous Cell; Carotenoids; Head and Neck Neoplasms; Humans; Isotretinoin

The antioxidant alpha-tocopherol and the weaker antioxidant and prooxidant chemopreventative, beta-carotene have been shown to inhibit tumor cell growth in vivo and in vitro. In some epidemiologic studies their serum levels were demonstrated to be inversely related to the incidence of malignant tumor. We hypothesized two basic pathways triggered by antioxidants and prooxidants, which resulted in the control of tumor cell growth. These included changes in phosphorylation and ultimately transcription. Specifically, the prooxidant beta-carotene treatment produced an oxidative stress resulting in the selective induction of heat shock proteins (hsps). These proteins and other proteins that were possibly oxidized were associated with the increased expression of cyclins (A and D) and increased cdc2 kinase expression. An increase in expression of phosphoproteins, such as p53 (tumor suppressor form) was also discerned. The level of expression for the transcription factor c-fos was reduced. Growth factors that contribute to tumor cell growth were also reduced. Increased DNA fragmentation, depression of proliferation and intracellular calcium levels, the accumulation of tumor cells in G0-->G1, and morphologic changes, were consistent with programmed cell death. Antioxidants such as alpha-tocopherol bound to membrane-associated proteins could inhibit the development of peroxidation products (hydroxyl radicals (.OH)), which attack proteins and modify their function and promote their degradation. Some kinases such as, cdc2 may be increased in activity, which would explain the observed increased expression of tumor suppressor p53, the accumulation of the tumor cells in G1 of the cell cycle and the inhibition of tumor cell proliferation. A reduction in oxidant radicals could also reduce transcription factor products, such as c-myb. Indirectly this result may occur through changes in nuclear translocation (signaling) NF-AT or the Rel-related family of transcription factors, including NF-kB (p50 or p65) or inhibition of immunophilin-calmodulin activity. Although the data remains fragmentary there are common points for control for tumor cell growth resulting from the effects of alpha-tocopherol or beta-carotene treatment. These changes involve phosphorylation and protein expression. Ultimately there is a reduction of important transcription factor protein products, a reduction in response to growth factors, and suppression of cell proliferation, resulting in increased contr

Topics: Animals; Apoptosis; beta Carotene; Carcinoma, Squamous Cell; Carotenoids; CDC2 Protein Kinase; Cell Division; Cricetinae; Gene Expression Regulation, Neoplastic; Genes, p53; Genes, ras; Heat-Shock Proteins; Humans; Mouth Neoplasms; Oxidation-Reduction; Proto-Oncogenes; Tumor Cells, Cultured; Vitamin E

Topics: Alcohol Drinking; Animals; Anticarcinogenic Agents; beta Carotene; Carcinoma, Squamous Cell; Carotenoids; Cell Differentiation; Clinical Trials as Topic; Cricetinae; Diet; Drug Screening Assays, Antitumor; Head and Neck Neoplasms; Humans; Leukoplakia, Oral; Mesocricetus; Respiratory Tract Neoplasms; Smoking; United States; Vitamin A

Topics: Aging; Animals; Antioxidants; beta Carotene; Carcinogens; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Carotenoids; DNA; Female; Geography; Humans; Male; Melanocytes; Melanoma; Neoplasms, Radiation-Induced; Pyrimidine Dimers; Sex Factors; Skin Neoplasms; Ultraviolet Rays; Vitamin A

Previous studies have found associations between one-carbon metabolism nutrients and risk of several cancers, but little is known regarding upper gastrointestinal tract (UGI) cancer. We analyzed prediagnostic serum concentrations of several one-carbon metabolism nutrients (vitamin B12, folate, vitamin B6, riboflavin and homocysteine) in a nested case-control study within the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study of male smokers, which was undertaken in Finland between 1985 and 1988. We conducted a nested case-control study including 127 noncardia gastric adenocarcinoma (NCGA), 41 esophagogastric junctional adenocarcinoma and 60 esophageal squamous cell carcinoma incident cases identified within ATBC. Controls were matched to cases on age, date of serum collection and follow-up time. One-carbon nutrient concentrations were measured in fasting serum samples collected at baseline (up to 17 years prior to cancer diagnosis). Odds ratios and 95% confidence intervals (CI) were calculated using conditional logistic regression. Lower prediagnostic vitamin B12 concentrations at baseline were associated with a 5.8-fold increased risk of NCGA (95% CI = 2.7-12.6 for lowest compared to highest quartile, p-trend <0.001). This association remained in participants who developed cancer more than 10 years after blood collection, and after restricting the analysis to participants with clinically normal serum vitamin B12 (>300 pmol/L). In contrast, pepsinogen I, a known serologic marker of gastric atrophy, was not associated with NCGA in this population. As vitamin B12 absorption requires intact gastric mucosa to produce acid and intrinsic factor, our findings suggest vitamin B12 as a possible serologic marker for the atrophic gastritis that precedes NCGA, one more strongly associated with subsequent NCGA than pepsinogen.

Topics: Aged; alpha-Tocopherol; beta Carotene; Carcinoma, Squamous Cell; Case-Control Studies; Dietary Supplements; Esophageal Neoplasms; Esophageal Squamous Cell Carcinoma; Finland; Folic Acid; Homocysteine; Humans; Male; Middle Aged; Prospective Studies; Riboflavin; Stomach Neoplasms; Vitamin B 12; Vitamin B 12 Deficiency

The purpose of the study was to identify factors associated with weight loss during radiotherapy (RT) in patients with stage I or II head and neck (HN) cancer.. This study was conducted as part of a phase III chemoprevention trial. A total of 540 patients were randomized. The patients were weighed before and after RT. Patients' characteristics, dietary intake, health-related quality of life (HRQOL), tumor characteristic, treatment characteristics, and acute adverse effects of RT were evaluated at baseline and during RT. Factors independently associated with weight loss during RT were identified using the multiple linear regression (P ≤ 0.05).. The mean weight loss during RT was 2.2 kg (standard deviation, 3.4). In bivariate analyses, the occurrence of adverse effects of RT and most of the HRQOL dimensions evaluated during RT were correlated with weight loss. In the multivariate analysis, eight factors were associated with a greater weight loss: all HN cancer sites other than the glottic larynx (P < 0.001), TNM stage II disease (P = 0.01), higher pre-RT body weight (P < 0.001), dysphagia before RT (P < 0.005), higher mucosa adverse effect of RT (P = 0.03), lower dietary energy intake during RT (P < 0.001), lower score of the digestive dimension on the Head and Neck Radiotherapy Questionnaire (P < 0.001) and a higher score of the constipation symptom on the EORTC QLQ-C30 during RT (P = 0.02).. The results underline the importance of maintaining energy intake in early stage HN cancer patients during RT and the importance of preventing and treating adverse effects.

Topics: alpha-Tocopherol; beta Carotene; Body Weight; Carcinoma, Squamous Cell; Causality; Chemoprevention; Chemoradiotherapy; Comorbidity; Double-Blind Method; Eating; Female; Head and Neck Neoplasms; Humans; Male; Middle Aged; Mucositis; Neoplasm Staging; Neoplasms, Second Primary; Population Surveillance; Quality of Life; Radiotherapy; Risk Factors; Surveys and Questionnaires; Weight Loss

The risk of malignant transformation of oral preneoplastic lesion (OPL) is difficult to assess. DeltaNp63 is an early oncoprotein associated with mucosal tumorigenesis. The purpose of this study was to assess DeltaNp63 expression in OPL and its role as a marker of oral cancer risk.. DeltaNp63 expression was determined using immunohistochemistry in 152 OPL patients included in a clinical trial comparing retinyl palmitate alone or plus beta-carotene with low-dose 13-cis-retinoic acid. The associations between DeltaNp63 expression as well as DeltaNp63 expression with other potential risk factors for oral cancer development were analyzed.. DeltaNp63 expression was positive in 41 (27%) patients, clusters of intraepithelial inflammatory cells (EIC) were noted in 37 (26%) patients, and podoplanin (previously reported) was positive in 56 (37%) patients. Significantly more patients whose lesions were DeltaNp63 positive or exhibited EIC developed oral cancers. In the multicovariate analysis including age, treatment, and histologic status as cofactors, positive DeltaNp63 expression was associated with an increased hazard ratio of 3.308 (95% confidence interval, 1.663-6.580; P = 0.0007). Patients whose lesions showed positive DeltaNp63, podoplanin, and EIC had the highest oral cancer risk with a hazard ratio of 4.372 (95% confidence interval, 1.912-9.992; P = 0.0005) and 61% oral cancer development rate at 5 years compared with 15% of other OPL patients (P < 0.0001).. DeltaNp63 overepression in OPL is associated with increased oral cancer risk. Together, DeltaNp63, podoplanin, and EIC may be used as biomarkers to identify OPL patients with substantially high oral cancer risk.

Topics: Antineoplastic Combined Chemotherapy Protocols; beta Carotene; Biomarkers, Tumor; Carcinoma, Squamous Cell; Diterpenes; Female; Follow-Up Studies; Gene Expression Regulation, Neoplastic; Genetic Predisposition to Disease; Humans; Inflammation; Isotretinoin; Leukoplakia, Oral; Male; Membrane Glycoproteins; Middle Aged; Mouth Neoplasms; Prognosis; Retinyl Esters; Trans-Activators; Transcription Factors; Tumor Suppressor Proteins; Up-Regulation; Vitamin A

Beta-carotene has established efficacy in animal models of oral carcinogenesis and has been shown to regress oral precancerous lesions in humans. The purpose of this study was to see whether these effects extended to the prevention of oral/pharyngeal/laryngeal (head and neck) cancer in humans. The subject population for this randomized, placebo-controlled, double-blinded clinical trial included 264 patients who had been curatively treated for a recent early-stage squamous cell carcinoma of the oral cavity, pharynx, or larynx. Patients were assigned randomly to receive 50 mg of beta-carotene per day or placebo and were followed for up to 90 months for the development of second primary tumors and local recurrences. After a median follow-up of 51 months, there was no difference between the two groups in the time to failure [second primary tumors plus local recurrences: relative risk (RR), 0.90; 95% confidence interval (CI), 0.56-1.45]. In site-specific analyses, supplemental beta-carotene had no significant effect on second head and neck cancer (RR, 0.69; 95% CI, 0.39-1.25) or lung cancer (RR, 1.44; 95% CI, 0.62-3.39). Total mortality was not significantly affected by this intervention (RR, 0.86; 95% CI, 0.52-1.42). Whereas none of the effects were statistically significant, the point estimates suggested a possible decrease in second head and neck cancer risk but a possible increase in lung cancer risk. These effects are consistent with the effects observed in trials using intermediate end point biological markers in humans, in which beta-carotene has established efficacy in oral precancerous lesions but has no effect or slightly worsens sputum cytology, and in animal carcinogenicity studies, in which beta-carotene has established efficacy in buccal pouch carcinogenesis in hamsters but not in animal models of respiratory tract/lung carcinogenesis, with some suggestions of tumor-promoting effects in respiratory tract/lung. If our results are replicated by other ongoing/completed trials, this suggests a critical need for mechanistic studies addressing differential responses in one epithelial site (head and neck) versus another (lung).

Topics: Adult; Aged; Anticarcinogenic Agents; Antioxidants; beta Carotene; Carcinoma, Squamous Cell; Dietary Supplements; Double-Blind Method; Female; Head and Neck Neoplasms; Humans; Male; Middle Aged; Neoplasms, Second Primary; Placebos

Although basic research provides plausible mechanisms for benefits of beta carotene supplementation on nonmelanoma skin cancer (NMSC) primarily consisting of basal cell carcinoma (BCC) and squamous cell carcinoma (SCC), observational studies are inconsistent. Randomized trial data are limited to 1 trial of secondary prevention that showed no effect of beta carotene on the incidence of NMSC after 5 years.. To test whether supplementation with beta carotene reduces the risk for development of a first NMSC, including BCC and SCC.. Randomized, double-blind, placebo-controlled trial with 12 years of beta carotene supplementation and follow-up.. Physicians' Health Study in the United States.. Apparently healthy male physicians aged 40 to 84 years in 1982 (N = 22 071).. Beta carotene, 50 mg, on alternate days.. Relative risk (RR) and 95% confidence interval (CI) for a first NMSC, BCC, and SCC.. After adjusting for age and randomized aspirin assignment, there was no effect of beta carotene on the incidence of a first NMSC (RR, 0.98; 95% CI, 0.92-1.05), BCC (RR, 0.99; 95% CI, 0.92-1.06), or SCC (RR, 0.97; 95% CI, 0.84-1.13). There was also no significant evidence of beneficial or harmful effects of beta carotene on NMSC by smoking status (current, past, or never).. This large-scale, randomized, primary prevention trial among apparently healthy well-nourished men indicates that an average of 12 years of supplementation with beta carotene does not affect the development of a first NMSC, including BCC and SCC.

Topics: Adult; Aged; Aged, 80 and over; Antioxidants; beta Carotene; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Cohort Studies; Dietary Supplements; Double-Blind Method; Follow-Up Studies; Humans; Incidence; Male; Middle Aged; Primary Prevention; Skin Neoplasms; United States

The use of sunscreens on the skin can prevent sunburn but whether long-term use can prevent skin cancer is not known. Also, there is evidence that oral betacarotene supplementation lowers skin-cancer rates in animals, but there is limited evidence of its effect in human beings.. In a community-based randomised trial with a 2 by 2 factorial design, individuals were assigned to four treatment groups: daily application of a sun protection factor 15-plus sunscreen to the head, neck, arms, and hands, and betacarotene supplementation (30 mg per day); sunscreen plus placebo tablets; betacarotene only; or placebo only. Participants were 1621 residents of Nambour in southeast Queensland, Australia. The endpoints after 4.5 years of follow-up were the incidence of basal-cell and squamous-cell carcinomas both in terms of people treated for newly diagnosed disease and in terms of the numbers of tumours that occurred. Analysis of the effect of sunscreen was based only on skin cancers that developed on sites of daily application. All analyses were by intention to treat.. 1383 participants underwent full skin examination by a dermatologist in the follow-up period. 250 of them developed 758 new skin cancers during the follow-up period. There were no significant differences in the incidence of first new skin cancers between groups randomly assigned daily sunscreen and no daily sunscreen (basal-cell carcinoma 2588 vs 2509 per 100,000; rate ratio 1.03 [95% CI 0.73-1.46]; squamous-cell carcinoma 876 vs 996 per 100,000; rate ratio 0.88 [0.50-1.56]). Similarly, there was no significant difference between the betacarotene and placebo groups in incidence of either cancer (basal-cell carcinoma 3954 vs 3806 per 100,000; 1.04 [0.73-1.27]; squamous-cell carcinoma 1508 vs 1146 per 100,000; 1.35 [0.84-2.19]). In terms of the number of tumours, there was no effect on incidence of basal-cell carcinoma by sunscreen use or by betacarotene but the incidence of squamous-cell carcinoma was significantly lower in the sunscreen group than in the no daily sunscreen group (1115 vs 1832 per 100,000; 0.61 [0.46-0.81]).. There was no harmful effect of daily use of sunscreen in this medium-term study. Cutaneous squamous-cell carcinoma, but not basal-cell carcinoma seems to be amenable to prevention through the routine use of sunscreen by adults for 4.5 years. There was no beneficial or harmful effect on the rates of either type of skin cancer, as a result of betacarotene supplementation.

Topics: Adult; Aged; beta Carotene; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Drug Therapy, Combination; Female; Follow-Up Studies; Humans; Male; Middle Aged; Neoplasms, Radiation-Induced; Queensland; Skin Neoplasms; Sunscreening Agents

Higher blood levels of alpha-tocopherol, the predominant form of vitamin E, have been associated in some studies with a reduced risk of lung cancer, but other studies have yielded conflicting results. To clarify this association, we examined the relationship between prospectively collected serum alpha-tocopherol and lung cancer in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study cohort.. The ATBC Study was a randomized, clinical trial of 29 133 white male smokers from Finland who were 50-69 years old and who had received alpha-tocopherol (50 mg), beta-carotene (20 mg), both, or neither daily for 5-8 years. Data regarding medical histories, smoking, and dietary factors were obtained at study entry, as was a serum specimen for baseline alpha-tocopherol determination. alpha-Tocopherol measurements were available for 29 102 of the men, among whom 1144 incident cases of lung cancer were diagnosed during a median observation period of 7.7 years. The association between alpha-tocopherol and lung cancer was evaluated with the use of multivariate proportional hazards regression.. A 19% reduction in lung cancer incidence was observed in the highest versus lowest quintile of serum alpha-tocopherol (relative risk = 0.81; 95% confidence interval = 0. 67-0.97). There was a stronger inverse association among younger men (<60 years), among men with less cumulative tobacco exposure (<40 years of smoking), and possibly among men receiving alpha-tocopherol supplementation.. In the ATBC Study cohort, higher serum alpha-tocopherol status is associated with lower lung cancer risk; this relationship appears stronger among younger persons and among those with less cumulative smoke exposure. These findings suggest that high levels of alpha-tocopherol, if present during the early critical stages of tumorigenesis, may inhibit lung cancer development.

Topics: Adenocarcinoma; Aged; beta Carotene; Carcinoma; Carcinoma, Small Cell; Carcinoma, Squamous Cell; Dietary Supplements; Finland; Humans; Lung Neoplasms; Male; Middle Aged; Prospective Studies; Risk; Risk Factors; Smoking; Treatment Outcome; Vitamin E

Epidemiological studies suggest that individuals with basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) of the skin are more likely to develop other malignancies; however, the factors responsible for this are unknown. To clarify the risk of other cancers following the occurrence of BCC and SCC, we followed participants in a multicenter skin cancer prevention trial for subsequent malignancies. The study group consisted of 1805 BCC and SCC patients who had enrolled in a trial testing the efficacy of oral beta-carotene. Medical confirmation was sought for all cancers (other than BCC or SCC), which were reported by participants or their next-of-kin over a follow-up period of 10 years. We computed the rate ratio (RR) and 95% confidence interval (CI) of time to first new, primary cancer in relation to history of BCC and SCC, using a proportional hazards model. A total of 235 participants had a new primary invasive cancer during 13,887 person-years of follow up. The risk of other cancers was modestly elevated in patients with one or more previous SCCs compared with those who only had a history of BCC (adjusted RR, 1.37; 95% CI, 0.91-2.07). Risk of other cancers also appeared to be increased among those who had multiple prior BCCs relative to those who had only one prior BCC (adjusted RR, 1.21; 95% CI, 0.91-1.61). Further adjustment for smoking history, Quetelet index, radiotherapy, extent of actinic skin damage, treatment assignment, or baseline beta-carotene concentrations did not appreciably alter the results. Cancer of the respiratory system was most strongly related to previous SCC or multiple BCC [RRs (95% CI), 2.20 (1.05-4.62) and 2.34 (1.14-4.83), respectively]. Our data suggest that unidentified exposures or inherited risk factors may play a common etiological role in the pathogenesis of nonmelanoma skin cancer and other cancers, especially respiratory cancers, although larger studies would be necessary to exclude the role of chance in these findings.

Topics: Aged; Anticarcinogenic Agents; beta Carotene; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Female; Humans; Incidence; Male; Middle Aged; Neoplasms, Second Primary; Proportional Hazards Models; Risk Factors; SEER Program; Skin Neoplasms

Topics: Antioxidants; beta Carotene; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Combined Modality Therapy; Cryotherapy; Humans; Retinoids; Skin Neoplasms

The Nambour Skin Cancer and Actinic Eye Disease Prevention Trial (the Nambour Trial) is a field trial conducted in an unselected adult population in Australia. Using a randomized 2 x 2 factorial design, the principal aim is to evaluate whether regular use of high-protection sunscreen and/or dietary supplementation with beta-carotene (30 mg daily) can alter the incidence rates of basal cell carcinomas and squamous cell carcinomas of the skin over a minimum follow-up time of 4.5 years. Changes in the incidence of solar keratoses and actinic eye disease and the rate of photoaging after intervention will also be investigated. In 1992, 1626 participants between the ages of 25 and 75 years were enrolled, all of whom had been randomly selected from residents of the southeastern Queensland township of Nambour for an earlier skin cancer prevalence survey. This paper describes the background to the trial and its design, with respect to evaluation of effects on actinic skin disease, and documents the baseline characteristics of participants recruited into the Nambour Trial.

Topics: Adult; Aged; beta Carotene; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Carotenoids; Cataract; Female; Humans; Male; Middle Aged; Patient Compliance; Skin Neoplasms; Sunscreening Agents; Ultraviolet Rays

Topics: Adult; beta Carotene; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Carotenoids; Diet; Double-Blind Method; Female; Follow-Up Studies; Humans; Life Style; Male; Middle Aged; Risk Factors; Sex Factors; Skin Neoplasms; Smoking; Surveys and Questionnaires; United States

High-dose isotretinoin therapy has been determined to be an effective treatment for leukoplakia. However, a high rate of relapses and toxic reactions led us to conduct a trial of a much lower dose of isotretinoin in the hope of maintaining a response and limiting toxicity.. In the first phase of the study, 70 patients with leukoplakia underwent induction therapy with a high dose of isotretinoin (1.5 mg per kilogram of body weight per day) for three months; in the second phase, patients with responses or stable lesions were randomly assigned to maintenance therapy with either beta carotene (30 mg per day) or a low dose of isotretinoin (0.5 mg per kilogram per day) for nine months.. In the first phase, the rate of response to high-dose induction therapy in the 66 patients who could be evaluated was 55 percent (36 patients). The lesions of seven patients progressed, and therefore they did not participate in the second phase of the trial. Of the 59 patients included in the second phase, 33 were assigned to beta carotene therapy and 26 to low-dose isotretinoin therapy; these two groups did not differ significantly in prognostic factors. Of the 53 patients who could be evaluated, 22 in the low-dose isotretinoin group and 13 in the beta carotene group responded to maintenance therapy or continued to have stable lesions (92 percent vs. 45 percent, P < 0.001). In situ carcinoma developed in one patient in each group, and invasive squamous-cell carcinoma in five patients in the beta carotene group. Toxicity was generally mild, though greater in the group given low-dose isotretinoin therapy.. When preceded by high-dose induction therapy, low-dose isotretinoin therapy was significantly more active against leukoplakia than beta carotene and was easily tolerated.

Topics: Adult; Aged; Aged, 80 and over; beta Carotene; Carcinoma, Squamous Cell; Carotenoids; Female; Head and Neck Neoplasms; Humans; Immunologic Factors; Isotretinoin; Leukoplakia, Oral; Male; Middle Aged; Mouth Neoplasms; Remission Induction

Topics: Administration, Oral; Anticarcinogenic Agents; beta Carotene; Carcinoma, Squamous Cell; Carotenoids; Connecticut; Diet Surveys; Double-Blind Method; Female; Follow-Up Studies; Head and Neck Neoplasms; Humans; Incidence; Male; Neoplasm Recurrence, Local; Neoplasms, Second Primary; Patient Compliance; Risk Factors; Treatment Failure

The primary aims of this study were to assess risk of subsequent basal and squamous cell skin cancer among patients with a prior history of these tumors and to examine these risks in relation to patient characteristics and life-style factors.. Follow-up of participants in a randomized trial of betacarotene as a possible skin cancer preventive agent.. Clinical centers in Los Angeles, Calif, San Francisco, Calif, Minneapolis, Minn, and Hanover, NH.. Patients (n = 1805) who were diagnosed as having a basal or squamous cell skin cancer between January 1980 and February 1986 and were free of skin cancer at study entry.. Time from study entry to first new occurrence of basal and squamous cell skin cancer.. The estimated risk of developing one or more new skin cancers was 35% at 3 years and 50% at 5 years. New skin cancers tended to be of the same cell type as the previous skin cancers. For both basal and squamous cell skin cancer, risk was higher among patients who were male, were over the age of 60 years, had more prior skin cancers, had severe actinic skin damage, or who burned easily with sun exposure. Compared with those who had never smoked, the rate of subsequent squamous cell skin cancer was higher among current smokers (rate ratio, 2.01; 95% confidence interval, 1.21 to 3.34) and former smokers (rate ratio, 1.62; 95% confidence interval, 1.07 to 2.47) and increased with both duration and amount smoked. There was no clear relationship between smoking and basal cell skin cancer; the rate appeared lower among heavy smokers but was unrelated to duration of smoking.. Persons with a prior nonmelanoma skin cancer had a substantial 5-year risk of developing another tumor of the same histologic type. Number of previous skin cancers, solar damage, and skin sensitivity to sun exposure were particularly related to this risk. The increased risk of squamous cell skin cancer associated with cigarette smoking merits further study.

Topics: Adult; Aged; Aged, 80 and over; beta Carotene; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Carotenoids; Female; Follow-Up Studies; Humans; Male; Middle Aged; Neoplasm Recurrence, Local; Probability; Risk Factors; Sex Factors; Skin Neoplasms; Smoking

Previous studies suggest that chronic oral administration of retinol and other retinoids causes elevation of plasma triglyceride concentrations. The effects of chronic oral administration of beta-carotene, a carotenoid partially metabolized to retinol, on plasma lipid concentrations have not been well studied; therefore, we studied 61 subjects over 12 mo while they were enrolled in a skin-cancer-prevention study in which patients were randomly assigned to receive either placebo (n = 30) or 50 mg beta-carotene/d orally (n = 31). At study entry and 1 y later, fasting blood samples were obtained for measurement of triglycerides, total cholesterol, HDL cholesterol, retinol, and beta-carotene. Retinol concentrations changed minimally in both groups; beta-carotene concentration increased an average of 12.1 +/- 47 nmol/L in the placebo group and 4279 +/- 657 nmol/L in the active-treatment group. Both groups experienced similar small increases in triglyceride and total cholesterol concentrations and small decreases in HDL cholesterol. Daily oral administration of 50 mg beta-carotene/d did not affect plasma lipid concentrations.

Topics: Administration, Oral; beta Carotene; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Carotenoids; Cholesterol; Cholesterol, HDL; Humans; Lipids; Skin Neoplasms; Triglycerides; Vitamin A

Beta carotene has been associated with a decreased risk of human cancer in many studies employing dietary questionnaires or blood measurements, and it has had protective effects in some animal models of carcinogenesis.. We tested the possible cancer-preventing effects of beta carotene by randomly assigning 1805 patients who had had a recent nonmelanoma skin cancer to receive either 50 mg of beta carotene or placebo per day and by conducting annual skin examinations to determine the occurrence of new nonmelanoma skin cancer.. Adherence to the prescribed treatment was good, and after one year the actively treated group's median plasma beta carotene level (3021 nmol per liter) was much higher than that of the control group (354 nmol per liter). After five years of follow-up, however, there was no difference between the groups in the rate of occurrence of the first new nonmelanoma skin cancer (relative rate, 1.05; 95 percent confidence interval, 0.91 to 1.22). In subgroup analyses, active treatment showed no efficacy either in the patients whose initial plasma beta carotene level was in the lowest quartile or in those who currently smoked. There was also no significant difference between treated and control groups in the mean number of new nonmelanoma skin cancers per patient-year.. In persons with a previous nonmelanoma skin cancer, treatment with beta carotene does not reduce the occurrence of new skin cancers over a five-year period of treatment and observation.

Topics: Aged; beta Carotene; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Carotenoids; Drug Evaluation; Female; Follow-Up Studies; Humans; Male; Patient Compliance; Randomized Controlled Trials as Topic; Recurrence; Skin Neoplasms

We describe a randomized clinical trial of oral beta-carotene (50 mg/day) for preventing nonmelanoma skin cancer. It is a multicenter study conducted at sites in California, Minnesota, and New Hampshire. This report describes the design of the study, baseline characteristics of the 1805 randomized patients, changes in their plasma beta-carotene and retinol levels after 1 year of treatment, and plans for statistical analyses. Important features of this study are (1) a high proportion of potential subjects were found to be ineligible or chose not to enter the study, (2) the study agent is readily available over the counter and in common foods, and (3) nonmelanoma skin cancer is a relatively minor health concern for most patients. These considerations necessitated intensive efforts to encourage compliance with the study regimen. There are also some unusual statistical features of the study. One is that the study outcome is routinely assessed only at annual examinations, so the precise time of failure cannot be identified. Also, a secondary goal of the study is to determine whether beta-carotene decreases the average number of new skin cancers per patient per year, and there are no established statistical methods for analysis of data in this situation. Alternative approaches to the analysis are discussed.

Topics: Adult; Aged; Aged, 80 and over; beta Carotene; Carcinoma, Squamous Cell; Carotenoids; Clinical Trials as Topic; Double-Blind Method; Female; Follow-Up Studies; Humans; Male; Middle Aged; Multicenter Studies as Topic; Neoplasm Recurrence, Local; Random Allocation; Risk Factors; Skin Neoplasms; Time Factors

β-carotene, a type of terpenoid, has many metabolic and physiological functions. In particular, β-carotene has an antitumor effect. However, the efficacy of β-carotene against esophageal squamous cell carcinoma (ESCC) remains unclear. In our study, β-carotene inhibited the growth of ESCC cells and downregulated expression of the Caveolin-1 (Cav-1) protein. Cav-1 protein was expressed only in ESCC cells, not in Het-1A cells. Moreover, β-carotene triggered apoptosis, induced cell cycle G0⁄G1 phase arrest, and inhibited cell migration. To explore the mechanism involved in these processes, we further examined the effect of β-carotene on the Cav-1-mediated AKT/NF-κB pathway. The results showed that the level of AKT and NF-κB phosphorylation was dramatically inhibited, which led to an increase in the Bax/Bcl-2 ratio. Correspondingly, the activity of Caspase-3 was also enhanced. These data suggest that β-carotene has an antiproliferative role in ESCC cells and may be a promising chemotherapeutic agent for use against ESCC cells.

Topics: Apoptosis; beta Carotene; Carcinoma, Squamous Cell; Caveolin 1; Cell Line, Tumor; Esophageal Neoplasms; Humans; NF-kappa B; Proto-Oncogene Proteins c-akt; Signal Transduction

Recently, we reported that β-carotene exhibited anticancer activity against human esophageal squamous cell carcinoma cells in vitro. In the present study, we examined a novel therapeutic strategy by combining β-carotene with 5-fluorouracil (5-FU) in human esophageal cancer in vitro and in vivo, and elucidated the underlying mechanisms. We found that the combination of 5-FU and β-carotene displayed greater growth inhibitory effects than did either compound alone in esophageal squamous cell carcinoma (ESCC) cells. In addition, the combination of 5-FU and β-carotene displayed greater tumor growth inhibition in an Eca109 xenograft mouse model than did a single agent with low systemic toxicity. β-Carotene enhanced 5-FU-induced apoptosis. TUNEL staining revealed that the rate of TUNEL-positive cells was markedly increased in tumor tissues after treatment with 5-FU and β-carotene. Western blotting and immunohistochemistry revealed the down-regulation of Bcl-2 and PCNA and the up-regulation of Bax and caspase-3 in tumor tissues. Further studies demonstrated that the combined administration of 5-FU and β-carotene significantly down-regulated the protein levels of Cav-1, p-AKT, p-NF-κB, p-mTOR and p-p70S6K in Eca109 cells more effectively than did 5-FU alone. These data suggested that the combined therapy of 5-FU and β-carotene exerted synergistic antitumor effects in vivo and in vitro and could constitute a novel therapeutic treatment for ESCC.

Topics: Animals; Antineoplastic Agents; Apoptosis; beta Carotene; Carcinoma, Squamous Cell; Cell Line, Tumor; Cell Survival; Drug Therapy, Combination; Esophageal Neoplasms; Fluorouracil; Humans; Mice; Neoplasms, Experimental

Low-molecular-weight antioxidants are some of the most efficient agents of the skin defense mechanism against environmental factors, such as cosmic rays, smoke, and pollutants. The total skin concentrations of hydrophilic ascorbic and uric acids, as well as lipophilic α-tocopherol, β-carotene, and ubiquinol-10 antioxidants were determined by an HPLC-EC detector from 18 biopsies of human nonmelanoma skin carcinomas and 18 biopsies from skin areas adjacent to carcinomas. No significant differences in the concentrations of lipophilic antioxidants in both carcinomas and normal-looking skin areas adjacent to carcinomas were observed. On the contrary, ascorbic and uric acid concentrations were found to be 18 and 36% lower in carcinomas than in normal-looking skin areas, respectively. No statistical significance was observed between antioxidant concentrations and age, sex, phototype, profession, site of tumor, frequency, and time of UV light exposure either. Accordingly the antioxidant concentrations in both cancerous skin and adjacent normal-looking areas were found to be much higher than in normal skin, in contrast to literature data.

Topics: Adult; Aged; Aged, 80 and over; alpha-Tocopherol; Antioxidants; Ascorbic Acid; beta Carotene; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Female; Humans; Male; Middle Aged; Molecular Weight; Skin; Skin Neoplasms; Ubiquinone; Uric Acid

The aim was to evaluate roles of vitamin D3 (VD3) and beta-carotene (BC) in the development of esophageal squamous cell carcinoma (ESCC) in a high-risk area, Huai'an District, Huai'an City, China.. 100 new ESCC diagnosed cases from 2007 to 2008 and 200 residency- age-, and sex-matched healthy controls were recruited. Data were collected from questionnaires, including a food frequency questionnaire (FFQ) to calculate the BC intake, and reversed phase high-performance liquid chromatography (RP-HPLC) was used to measure the serum concentrations of BC and VD3. Odds ratios (OR) and 95% confidence intervals (CI) were calculated in conditional logistic regression models.. The average dietary intake of BC was 3322.9 μg (2032.4- 5734.3) in the case group and 3626.8 μg (1961.9-5827.9) in control group per capita per day with no significant difference by Wilcoxon test (p>0.05). However, the levels of VD3 and BC in the case group were significantly lower than in the control group (p<0.05). The OR values of the highest quartile and the lowest quartile of VD3 and BC in serum samples were both 0.13.. Our results add to the evidence that high circulating levels of VD3 and BC are associated with a reduced risk of ESCC in this Chinese population.

Topics: beta Carotene; Carcinoma, Squamous Cell; Case-Control Studies; China; Cholecalciferol; Chromatography, High Pressure Liquid; Esophageal Neoplasms; Female; Follow-Up Studies; Humans; Male; Middle Aged; Prognosis; Risk Factors

Some dietary factors could be involved as cofactors in cervical carcinogenesis, but evidence is inconclusive. There are no data about the effect of fruits and vegetables intake (F&V) on cervical cancer from cohort studies. We examined the association between the intake of F&V and selected nutrients and the incidence of carcinoma in situ (CIS) and invasive squamous cervical cancer (ISC) in a prospective study of 299,649 women, participating in the European Prospective Investigation into Cancer and Nutrition study. Cox proportional hazard models were used to estimate adjusted hazard ratios (HRs) and 95% confidence intervals (95% CI). A calibration study was used to control measurement errors in the dietary questionnaire. After a mean of 9 years of follow-up, 253 ISC and 817 CIS cases were diagnosed. In the calibrated model, we observed a statistically significant inverse association of ISC with a daily increase in intake of 100 g of total fruits (HR 0.83; 95% CI 0.72-0.98) and a statistically nonsignificant inverse association with a daily increase in intake of 100 g of total vegetables (HR 0.85: 95% CI 0.65-1.10). Statistically nonsignificant inverse associations were also observed for leafy vegetables, root vegetables, garlic and onions, citrus fruits, vitamin C, vitamin E and retinol for ISC. No association was found regarding beta-carotene, vitamin D and folic acid for ISC. None of the dietary factors examined was associated with CIS. Our study suggests a possible protective role of fruit intake and other dietary factors on ISC that need to be confirmed on a larger number of ISC cases.

Topics: Adult; Aged; Ascorbic Acid; beta Carotene; Carcinoma; Carcinoma, Squamous Cell; Diet; Europe; Female; Folic Acid; Follow-Up Studies; Fruit; Humans; Middle Aged; Neoplasm Invasiveness; Nutrition Surveys; Prospective Studies; Risk Factors; Uterine Cervical Neoplasms; Vegetables; Vitamin A; Vitamin D; Vitamin E

Although Iran is a high-risk region for esophageal squamous cell carcinoma (ESCC), dietary factors that may contribute to this high incidence have not been thoroughly studied. The aim of this study was to evaluate the effect of macronutrients, vitamins and minerals on the risk of ESCC.. In this hospital-based case-control study, 47 cases with incident ESCC and 96 controls were interviewed and usual dietary intakes were collected using a validated food frequency questionnaire. Data were modeled through unconditional multiple logistic regression to estimate odds ratios (OR) and 95% confidence intervals (CI), controlling for age, sex, gastrointestinal reflux, body mass index, smoking history (status, intensity and duration), physical activity, and education.. ESCC cases consumed significantly more hot foods and beverages and fried and barbecued meals, compared to the controls (p < 0.05). After adjusting for potential confounders, the risk of ESCC increased significantly in the highest tertiles of saturated fat [OR:2.88,95%CI:1.15-3.08], cholesterol [OR:1.53, 95%CI: 1.41-4.13], discretionary calorie [OR:1.51, 95%CI: 1.06-3.84], sodium [OR:1.49,95%CI:1.12-2.89] and total fat intakes [OR:1.48, 95%CI:1.09-3.04]. In contrast, being in the highest tertile of carbohydrate, dietary fiber and (n-3) fatty acid intake reduced the ESCC risk by 78%, 71% and 68%, respectively. The most cancer-protective effect was observed for the combination of high folate and vitamin E intakes (OR: 0.02, 95%CI: 0.00-0.87; p < 0.001). Controls consumed 623.5 times higher selenium, 5.48 times as much β-carotene and 1.98 times as much α-tocopherol as the amount ESCC cases consumed.. This study suggests that high intake of nutrients primarily found in plant-based foods is associated with a reduced esophageal cancer risk. Some nutrients such as folate, vitamin E and selenium might play major roles in the etiology of ESCC and their status may eventually be used as an epidemiological marker for esophageal cancer in Iran, and perhaps other high-risk regions.

Topics: Aged; alpha-Tocopherol; beta Carotene; Carcinoma, Squamous Cell; Case-Control Studies; Confidence Intervals; Diet; Dietary Carbohydrates; Dietary Fats; Dietary Fiber; Energy Intake; Esophageal Neoplasms; Feeding Behavior; Female; Folic Acid; Hospitalization; Humans; Incidence; Interviews as Topic; Iran; Logistic Models; Male; Micronutrients; Middle Aged; Odds Ratio; Pilot Projects; Risk Factors; Selenium; Surveys and Questionnaires; Vitamin E; Vitamins

The aim of our study was to compare plasma carotenoids (i.e., biomarkers of fruits and vegetables intake) and tocopherols in 29 head and neck squamous cell carcinoma (HNSCC) patients with 51 healthy controls and to explore the possibility whether these plasma antioxidants could be related to outcome among patients. The patients' blood samples were taken at the end of radiotherapy. We observed that plasma lutein, zeaxanthin, alpha-carotene, beta-carotene, lycopene, and total carotenoids were significantly lower in HNSCC patients than controls. Among the patients, 18 died and 11 were still alive during median follow-up of 55 mo for survivors. We found a significant positive association between postradiotherapy plasma carotenoids (lutein, alpha-carotene, and beta-carotene) and progression-free survival in these patients. This study indicates that increasing postradiotherapy plasma carotenoid concentration may reduce risk of premature death or recurrence of tumor in HNSCC patients. Increasing plasma carotenoid concentration should be done by increasing intake of carotenoid-rich fruits and vegetables, as other studies have shown either no or negative effects due to use of carotenoid supplements.

Topics: Adult; Aged; Aged, 80 and over; beta Carotene; Carcinoma, Squamous Cell; Carotenoids; Disease-Free Survival; Female; Head and Neck Neoplasms; Humans; Lutein; Male; Middle Aged; Tocopherols

Helicobacter pylori can induce gastric atrophy in humans, which in turn increases gastric cancer risk. Whether H. pylori and gastric atrophy also affect the risk of esophageal squamous cell carcinoma (ESCC), however, remains unresolved.. We performed a nested case-control study within the prospective Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study to assess these relationships. The Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study is composed of 29,133 Finnish male smokers, ages 50 to 69 years, who were recruited during 1985-1988. Using baseline sera, we assessed H. pylori status (via immunoglobulin G antibodies against whole-cell and CagA antigens) and gastric atrophy status [via the biomarkers pepsinogen I (PGI) and pepsinogen II (PGII)] in 79 ESCC cases and 94 controls. Logistic regression with adjustment for age, date of blood draw, education, cigarette smoking, alcohol, body mass index, and fruit and vegetable intake was used to estimate odds ratios (OR) and 95% confidence intervals (95% CI).. Gastric atrophy (PGI/PGII <4) was associated with ESCC (OR, 4.58; 95% CI, 2.00-10.48). There was no evidence for an association between H. pylori and ESCC (OR, 0.94; 95% CI, 0.40-2.24).. These results could be explained by misclassification of H. pylori status due to serologic amnesia, ESCC risk being dependent on the functional consequences or interactions of H. pylori rather than the infection per se, gastric atrophy having a different histogenesis in ESCC without being primarily dependent on H. pylori acquisition, or a lack of statistical power to detect an effect.. Validation of these results may warrant mechanistic studies to determine the route of association between gastric atrophy and ESCC.

Topics: Aged; alpha-Tocopherol; Atrophy; beta Carotene; Biomarkers; Carcinoma, Squamous Cell; Case-Control Studies; Esophageal Neoplasms; Finland; Helicobacter pylori; Humans; Male; Middle Aged; Pepsinogens; Randomized Controlled Trials as Topic; Risk; Smoking; Stomach

Studies have suggested that retinoids prevent lung cancer by interacting with nuclear retinoid receptors. However, clinical trials with beta-carotene increased lung cancer mortality. We recently showed that beta-carotene stimulates the proliferation of small airway-derived adenocarcinoma by increasing cAMP signaling. Here, we have tested the hypothesis that beta-carotene may stimulate squamous cell carcinoma cells via similar mechanisms. We determined the effects of beta-carotene in cell lines from squamous cell carcinomas and large airway epithelia on proliferation by MTT assays in the presence and absence of inhibitors. Signaling via cAMP/PKA was measured by immunoassays and PKA activation assay. Phosphorylated ERK1/2 was determined by Western blotting. beta-carotene significantly inhibited proliferation and phosphorylation of ERK1/2 by Galphas-mediated signaling involving adenylyl cyclase, cAMP, PKA and ERK1/2. These findings introduce a non-genomic inhibitory mechanism of beta-carotene and emphasize the need for the development of marker-guided lung cancer prevention.

Topics: beta Carotene; Carcinoma, Squamous Cell; Cell Line, Tumor; Cell Proliferation; Cyclic AMP; Cyclic AMP-Dependent Protein Kinases; Gene Expression Regulation, Neoplastic; Humans; Immunoassay; Lung Neoplasms; Models, Biological; Phosphorylation; Signal Transduction; Tetrazolium Salts; Thiazoles; Time Factors

Differential diagnosis for epithelial tissues of normal human gastric, undifferentiation gastric adenocarcinoma, gastric squamous cell carcinomas, and poorly differentiated gastric adenocarcinoma were studied using the Kubelka-Munk spectral function of the DNA and protein absorption bands at 260 and 280 nm in vitro. Diffuse reflectance spectra of tissue were measured using a spectrophotometer with an integrating sphere attachment. The results of measurement showed that for the spectral range from 250 to 650 nm, pathological changes of gastric epithelial tissues induced that there were significant differences in the averaged value of the Kubelka-Munk function f(r infinity) and logarithmic Kubelka-Munk function log[f(r infinity)] of the DNA absorption bands at 260 nm between epithelial tissues of normal human stomach and human undifferentiation gastric cancer, between epithelial tissues of normal human stomach and human gastric squamous cell carcinomas, and between epithelial tissues of normal human stomach and human poorly differentiated cancer. Their differences were 68.5% (p < 0.05), 146.5% (p < 0.05), 282.4% (p < 0.05), 32.4% (p < 0.05), 56.00 (p < 0.05) and 83.0% (p < 0.05) respectively. And pathological changes of gastric epithelial tissues induced that there were significant differences in the averaged value of the Kubelka-Munk function f(r infinity) and logarithmic Kubelka-Munk function log[f(r infinity)] of the protein absorption bands at 280 nm between epithelial tissues of normal human stomach and human undifferentiation gastric cancer, between epithelial tissues of normal human stomach and human gastric squamous cell carcinomas, and between epithelial tissues of normal human stomach and human poorly differentiated cancer. Their differences were 86.8% (p < 0.05), 262.9% (p < 0.05), 660.1% (p < 0.05) and 34% (p < 0.05), 72. 2% (p < 0.05), 113.5% (p < 0.05) respectively. And pathological changes of gastric epithelial tissues induced that there were significant differences in the averaged value of the Kubelka-Munk function f(r infinity) and logarithmic Kubelka-Munk function log[f(r infinity)] of the carotene absorption bands at 480 nm between epithelial tissues of normal human stomach and human undifferentiation gastric cancer, between epithelial tissues of normal human stomach and human gastric squamous cell carcinomas, and between epithelial tissues of normal human stomach and human poorly differentiated cancer. Their differences were 59.5% (p < 0

Topics: Adenocarcinoma; beta Carotene; Carcinoma, Squamous Cell; DNA; Gastric Mucosa; Humans; Proteins; Spectrophotometry; Stomach Neoplasms

Analysis of longitudinal data with excessive zeros has gained increasing attention in recent years; however, current approaches to the analysis of longitudinal data with excessive zeros have primarily focused on balanced data. Dropouts are common in longitudinal studies; therefore, the analysis of the resulting unbalanced data is complicated by the missing mechanism. Our study is motivated by the analysis of longitudinal skin cancer count data presented by Greenberg, Baron, Stukel, Stevens, Mandel, Spencer, Elias, Lowe, Nierenberg, Bayrd, Vance, Freeman, Clendenning, Kwan, and the Skin Cancer Prevention Study Group[New England Journal of Medicine 323, 789-795]. The data consist of a large number of zero responses (83% of the observations) as well as a substantial amount of dropout (about 52% of the observations). To account for both excessive zeros and dropout patterns, we propose a pattern-mixture zero-inflated model with compound Poisson random effects for the unbalanced longitudinal skin cancer data. We also incorporate an autoregressive of order 1 correlation structure in the model to capture longitudinal correlation of the count responses. A quasi-likelihood approach has been developed in the estimation of our model. We illustrated the method with analysis of the longitudinal skin cancer data.

Topics: Aged; Antioxidants; beta Carotene; Bias; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Carotenoids; Data Interpretation, Statistical; Drug Evaluation; Female; Follow-Up Studies; Humans; Incidence; Longitudinal Studies; Male; Patient Compliance; Randomized Controlled Trials as Topic; Recurrence; Skin Neoplasms

Experimental studies have consistently shown a protective effect of nonsteroidal antiinflammatory drugs (NSAIDs) against nonmelanoma skin cancers (NMSC). However, little human epidemiological research has been done in this regard. We used data from the Skin Cancer Chemoprevention Study to explore the association of NSAID use and with the risk of basal-cell carcinoma (BCC) and squamous-cell carcinoma (SCC). 1,805 subjects with a recent history of NMSC were randomized to placebo or 50 mg of daily beta-carotene. Participants were asked about their use of over-the-counter and prescription medications at baseline and every 4 months during the trial. Skin follow-up examinations were scheduled annually with a study dermatologist; confirmed lesions were the endpoints in the study. We used a risk set approach to the analysis of grouped times survival data and unconditional logistic regression to compute odds ratios [ORs] for various exposures to NSAIDs. The use of NSAIDs was reported in over 50% of questionnaires. For BCC, NSAIDs exhibited a weak protective effect in crude analyses, which attenuated markedly after adjustment. For SCC, the use of NSAIDs in the year previous to diagnosis reduced the odds by almost 30% (adjusted OR=0.71, 95% CI 0.48-1.04). When we accounted for frequency of use, results for BCC were not striking, and there were inconsistent suggestions of an inverse association with SCC. There were some indications of a modest, nonsignificant reduction on the number of BCCs and SCCs with NSAID use. Our data suggest a weak and inconsistent chemopreventive effect of NSAIDs on BCC and SCC.

Topics: Aged; Anti-Inflammatory Agents, Non-Steroidal; Anticarcinogenic Agents; Antioxidants; beta Carotene; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Female; Follow-Up Studies; Humans; Male; Middle Aged; Neoplasm Recurrence, Local; Odds Ratio; Randomized Controlled Trials as Topic; Regression Analysis; Risk Factors; Skin Neoplasms; Surveys and Questionnaires

This study examined the relationship between pretrial serum concentrations of retinol, beta-carotene, beta-cryptoxanthin, and lutein/zeaxanthin and the subsequent risk of developing esophageal squamous cell carcinoma and gastric cardia or non-cardia adenocarcinoma in subjects selected from a randomized nutritional intervention trial in Linxian, China, a region with epidemic rates of esophageal and gastric cardia cancer.. We used a stratified case-cohort design to select cohort members for inclusion in this study. In all we measured serum concentrations of the above vitamins in 590 esophageal, 395 gastric cardia, and 87 gastric non-cardia case subjects as well as in 1053 control subjects. Relative risks (RRs) were estimated using Cox proportional hazards models.. Median values in our cohort were low for serum retinol (33.6 microg/dl), beta-carotene (4.3 microg/dl), and beta-cryptoxanthin (3.5 microg/dl), but were high for lutein/zeaxanthin (40.0 microg/dl). Gastric cardia cancer incidence fell 10% for each quartile increase in serum retinol (RR = 0.90, 95% CI = 0.83-0.99). For esophageal cancer, an inverse association with retinol levels was found only in male non-smokers (RR = 0.79 per quartile increase, 95% CI = 0.63-0.99). For gastric non-cardia cancer, an inverse association was limited to subjects 50 years old or younger (RR = 0.58 per quartile, 95% CI = 0.31-0.96). For beta-cryptoxanthin there was a borderline significant protective association for gastric non-cardia cancer (RR = 0.88 per quartile, 95% CI = 0.76-1.0). In contrast, we found the incidence of gastric non-cardia cancer increased (RR = 1.2 per quartile, 95% CI = 1.0-1.3) with increasing concentration of serum lutein/zeaxanthin.. In this population, we found that low retinol and high lutein/zeaxanthin concentrations increased the risks of gastric cardia and gastric non-cardia cancer respectively. We found that there were no strong associations between any of the other analytes and any of the cancer sites.

Topics: Adenocarcinoma; Adult; Aged; beta Carotene; Carcinoma, Squamous Cell; China; Cryptoxanthins; Esophageal Neoplasms; Female; Humans; Lutein; Male; Middle Aged; Proportional Hazards Models; Prospective Studies; Regression Analysis; Risk Factors; Stomach Neoplasms; Vitamin A; Xanthophylls; Zeaxanthins

We have examined the role of dietary patterns and specific dietary nutrients in the etiology of lung cancer among non-smokers using a multicenter case-control study.. 506 non-smoking incident lung cancer cases were identified in the eight centers along with 1045 non-smoking controls. Dietary habits were assessed using a quantitative food-frequency questionnaire administered by personal interview. Based on this information, measures of total carotenoids, beta-carotene and retinol nutrient intake were estimated.. Protective effects against lung cancer were observed for high consumption of tomatoes, (odds ratio (OR) = 0.5; 95% confidence interval (CI) 0.4-0.6), lettuce (OR = 0.6; 95% CI 0.3-1.2), carrots (OR = 0.8; 95% CI 0.5-1.1), margarine (OR = 0.7; 95% CI 0.5-0.8) and cheese (OR = 0.7; 95% CI 0.5-1.0). Only weak protective effects were observed for high consumption of all carotenoids (OR = 0.8; 95% CI 0.6-1.0), beta-carotene (OR = 0.8; 95% CI 0.6-1.1) and retinol (OR = 0.9; 95% CI 0.7-1.1). Protective effects for high levels of fruit consumption were restricted to squamous cell carcinoma (OR = 0.7; 95% CI 0.4-1.2) and small cell carcinoma (OR = 0.7; 95% CI 0.4-1.2), and were not apparent for adenocarcinoma (OR = 0.9; 95% CI 0.6-1.3). Similarly, any excess risk associated with meat, butter and egg consumption was restricted to squamous and small cell carcinomas, but was not detected for adenocarcinomas.. This evidence suggests that the public health significance of increasing vegetable consumption among the bottom third of the population would include a reduction in the incidence of lung cancer among lifetime non-smokers by at least 25%, and possibly more. A similar protective effect for increased fruit consumption may be present for squamous cell and small cell lung carcinomas.

Topics: Adenocarcinoma; Adult; Aged; beta Carotene; Carcinoma, Small Cell; Carcinoma, Squamous Cell; Carotenoids; Case-Control Studies; Diet; Female; Humans; Incidence; Lung Neoplasms; Male; Middle Aged; Public Health; Smoking; Vegetables; Vitamin A

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

Topics: Adult; Aged; Antioxidants; beta Carotene; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Dietary Supplements; Female; Humans; Male; Middle Aged; Randomized Controlled Trials as Topic; Skin Neoplasms; Sunscreening Agents

To examine the protective role of dietary antioxidants (carotenoids, vitamin C, vitamin E, glutathione, and flavonoids) in lung cancer risk, a case-control study involving 541 cases of lung cancer and 540 hospitalized controls was carried out in Uruguay. The relevant variables were energy adjusted using the residuals method and then categorized in quartiles. Adjusted odds ratios (ORs) for antioxidants were calculated through unconditional logistic regression. With the exception of lycopene and vitamin C, the remaining antioxidants were associated with significant reductions in risk of lung cancer. Of particular interest was the inverse association between dietary glutathione and lung cancer [OR of quartile with highest intake compared with lowest quartile = 0.42, 95% confidence interval (CI) = 0.27-0.63]. Also, carotenoids and vitamin E were associated with significant reductions in risk of lung cancer (OR = 0.43, 95% CI = 0.29-0.64 for total carotenoids and OR = 0.50, 95% CI = 0.39-0.85 for vitamin E). A joint effect for high vs. low intakes of beta-carotene and glutathione was associated with a significant reduction in risk (OR = 0.32, 95% CI = 0.22-0.46). It could be concluded that dietary antioxidants are associated with a significant protective effect in lung carcinogenesis and that the inverse association for glutathione persisted after controlling for total vegetables and fruits.

Topics: Adenocarcinoma; Adult; Age Distribution; Aged; Aged, 80 and over; Antioxidants; beta Carotene; Carcinoma; Carcinoma, Large Cell; Carcinoma, Small Cell; Carcinoma, Squamous Cell; Case-Control Studies; Diet; Glutathione; Humans; Logistic Models; Lung Neoplasms; Male; Middle Aged; Odds Ratio; Risk Factors; Surveys and Questionnaires; Uruguay

Topics: Aldehydes; beta Carotene; Carcinoma, Squamous Cell; Cell Division; Cholesterol; Chromatography, High Pressure Liquid; Humans; Oxidation-Reduction; Tumor Cells, Cultured

We conducted a nested case-control study of squamous cell skin cancer (SCC) to determine whether risk was related to plasma concentrations of selenium, alpha-tocopherol, beta-carotene, and retinol. We derived the study sample from participants in our Skin Cancer Prevention Study, all of whom had at least one basal cell or squamous cell skin cancer before study entry. Those who developed a new squamous cell skin cancer during the 3-5-year follow-up period were selected as cases (n = 132). Controls (n = 264) were chosen at random, with matching by age, sex, and study center, from among those who did not develop SCC but were being followed actively at the time the SCC case was diagnosed. Prediagnostic plasma samples were analyzed for alpha-tocopherol, beta-carotene, and retinol using high-performance liquid chromatography. Selenium determinations were made using instrumental neutron activation analysis. Odds ratios were computed using conditional logistic regression for matched samples. We found no consistent pattern of SCC risk associated with any of the nutrients examined. The odds ratios (95% confidence intervals) for the highest versus the lowest quartiles of beta-carotene, retinol, alpha-tocopherol, and selenium were 0.73 (0.38-1.41), 1.43 (0.77-2.64), 0.89 (0.43-1.85), and 0.86 (0.47-1.58), respectively. Thus, our data add to the growing body of evidence that these nutrients, at the concentrations we evaluated, are not related strongly to SCC risk.

Topics: Adult; Aged; Aged, 80 and over; beta Carotene; Biomarkers, Tumor; Carcinoma, Squamous Cell; Case-Control Studies; Female; Humans; Logistic Models; Male; Middle Aged; Odds Ratio; Risk Factors; Selenium; Skin Neoplasms; Vitamin A; Vitamin E

Topics: Anticarcinogenic Agents; beta Carotene; Carcinoma, Squamous Cell; Cell Transformation, Neoplastic; Follow-Up Studies; Head and Neck Neoplasms; Humans; Isotretinoin; Mouth Neoplasms; Time Factors; Treatment Outcome

The carotenoids beta-carotene and canthaxanthin and the retinoid 13-cis-retinoic acid (13-RA) have inhibited oral carcinogenesis in the hamster cheek pouch (16 wks, 3 times/wk at 1.4 mg/kg) induced by an 0.5% solution of 7, 12-dimethylbenz[a]anthracene (DMBA). However, 13-RA at a higher dose (> 2.0 mg/kg per treatment) increased squamous cell carcinoma growth (Eur J Cancer Clin Oncol 24, 839-850, 1988). 13-RA, beta-carotene, and canthaxanthin administered to 60 hamsters (16 wks, 3 times/wk, 10 mg/kg) altered neovascularization characterized by immunohistochemistry for transforming growth factor-alpha (TGF-alpha) and factor VIII. 13-RA + DMBA resulted in more smaller-sized tumors, with a reduced volume and tumor burden (tumor controls, 185.9; 13-RA + DMBA, 151.0). The carotenoids reduced the number and the sizes of the carcinomas formed (beta-carotene, 60 tumors, 142.3 x 10(3) mm3; canthaxanthin, 30 tumors, 116.1 x 10(3) mm3). Factor VIII and TGF-alpha were expressed in high intensity at cancer sites of the 13-RA + DMBA and DMBA groups with > 50 and > 10 cells, respectively, per x 400 field. In contrast, beta-carotene- and canthaxanthin + DMBA-treated pouches showed > 20 and 5 cells, respectively, per x 400 field for factor VIII and TGF-alpha. These results suggest that 13-RA treatment may increase vascular growth, but the carotenoids also produced enhanced levels of endothelial cell growth and TGF-alpha compared with the untreated mucosa. The carotenoids may enhance tumor growth under the appropriate carcinogenic environment.

Topics: 9,10-Dimethyl-1,2-benzanthracene; Animals; beta Carotene; Canthaxanthin; Carcinoma, Squamous Cell; Cheek; Cricetinae; Dose-Response Relationship, Drug; Factor VIII; Immunoenzyme Techniques; Isotretinoin; Male; Mesocricetus; Mouth Mucosa; Mouth Neoplasms; Neovascularization, Pathologic; Transforming Growth Factor alpha

In order to discover the relationship between dietary nutrients intake and risk of lung cancer 1:1 matched case-control study on 156 recent histologiclly diagnosed primary lung cancer patients and 156 patients with respiratory tumour and other related diseases as controls, was conducted in Wuhan. All cases and controls were asked to participate in the nutritional assessment program and a food frequency questionnaire containing 64 food items was filled in. The findings showed that there was a statistically significant difference between dietary intake of beta-carotene between the two groups (2877.13 +/- 393.43 vs. 3445 +/- 430.98 micrograms/day). Having controled the confounding factor of cigarette smoking, a significant linear trend for lower dietary carotene intake toward higher lung cancer risk was observed.

Topics: Adenocarcinoma; beta Carotene; Carcinoma, Squamous Cell; Carotenoids; Case-Control Studies; China; Diet; Female; Humans; Lung Neoplasms; Male; Middle Aged; Nutrition Surveys; Risk Factors; Smoking

Screening examinations were conducted at a Chinese community health fair in Houston, Texas, to identify individuals with oral leukoplakia for a chemoprevention trial of oral-cavity squamous cell carcinoma. All 161 volunteer participants were interviewed regarding age, smoking habits, and betel-nut and alcohol use. The screening included an examination of the oral cavity, oropharynx, and neck. One participant had a 1-mm area of oral leukoplakia on the right lateral surface of the oral tongue. Eighteen participants had other head and neck abnormalities. Only 12 participants (7.5%) were active smokers, and eight (5%) reported a prior history of smoking. One participant reported prior betel-nut use. The mean age was 55 years. The authors conclude that a venue such as this has a low yield for screening and recruitment of high-risk individuals for chemoprevention of oral-cavity squamous cell carcinoma, that generally health-conscious individuals attend health fairs, and that only a small percentage volunteer for oral screening.

Topics: Adult; Aged; beta Carotene; Carcinoma, Squamous Cell; Carotenoids; China; Female; Health Fairs; Humans; Leukoplakia, Oral; Male; Middle Aged; Mouth Neoplasms; Smoking; Texas; Vitamin A

Topics: Antineoplastic Agents; beta Carotene; Carcinoma, Squamous Cell; Carotenoids; Cell Transformation, Neoplastic; Humans; Incidence; Lung Neoplasms

The ability of the collagenase inhibitor minocycline and of beta-carotene to act as positive modulators of cytotoxic anticancer agents was assessed in vitro and in vivo. Cell-culture studies were conducted using the human SCC-25 squamous carcinoma cell line. Simultaneous exposure of the cells to minocycline and beta-carotene or 13-cis-retinoic acid along with cisplatin (CDDP) resulted in a small decrease in the cytotoxicity of the CDDP. The addition of each of the modulator combinations for 1 h or 24 h to treatment with melphalan (L-PAM) or carmustine (BCNU) resulted in greater-than-additive cytotoxicity with each of four regimens. The modulator combinations of minocycline and beta-carotene applied for 1 h or 24 h and the modulator combination of minocycline and 13-cis-retinoic acid produced greater-than-additive cytotoxicity at 50 microM 4-hydroperoxycyclophosphamide (4-HC), whereas minocycline and 13-cis-retinoic acid applied for 1 h was antagonistic with 4-HC and the other modulator treatments at low concentrations of 4-HC resulted in subadditive cytotoxicity. The effect of treatment with beta-carotene alone and in combination with several different anticancer agents was examined in two murine solid tumors, the FSaII fibrosarcoma and the SCC VII carcinoma. Administration of the modulators alone or in combination did not alter the growth of either tumor. Whereas increases in tumor growth delay occurred with the antitumor alkylating agents and beta-carotene and with minocycline and beta-carotene, a diminution in tumor growth delay was produced by 5-fluorouracil in the presence of these modulators. The modulator combination also resulted in increased tumor growth delay with adriamycin and etoposide. Tumor-cell survival assay showed increased killing of FSaII tumor cells with the modulator combination and melphalan or cyclophosphamide as compared with the drugs alone. These results indicate that further investigation of this modulator strategy is warranted.

Topics: Animals; Antineoplastic Agents; beta Carotene; Carcinoma, Squamous Cell; Carotenoids; Dose-Response Relationship, Drug; Drug Interactions; Fibrosarcoma; Humans; Isotretinoin; Male; Mice; Mice, Inbred C3H; Minocycline; Tumor Cells, Cultured

The modifying effects of two natural products, curcumin and hesperidin, given during the initiation and postinitiation phases of oral carcinogenesis initiated with 4-nitroquinoline 1-oxide (4-NQO) were investigated in male F344 rats and compared with that of beta-carotene. At 6 weeks of age, rats were divided into experimental and control groups and fed the diet containing beta-carotene, hesperidin, or curcumin at a dose of 0.5 g/kg diet (500 ppm). At 7 weeks of age, all animals except those treated with each test chemical alone and control groups were given 4-NQO (20 ppm) in the drinking water for 8 weeks to induce oral cancer. Seven days after the 4-NQO exposure, groups of animals fed the diets containing test chemicals were switched to the basal diet and continued on this diet until the end of the study. Starting 1 week after the stop of 4-NQO exposure, the groups given 4-NQO and a basal diet were switched to the diets containing beta-carotene, hesperidin, and curcumin and maintained on these diets for 22 weeks. The other groups consisted of rats given 500 ppm beta-carotene, hesperidin, or curcumin alone or untreated rats. All animals were necropsied at the termination of the experiment (week 32). The incidences of tongue neoplasms and preneoplastic lesions, polyamine levels in the tongue tissue, and cell proliferation activity estimated by bromodeoxyuridine-labeling index and by morphometric analysis of silver-stained nucleolar organizer region proteins were compared among the groups. Feeding of curcumin and beta-carotene during the initiation and postinitiation phases and hesperidin at the initiation stage caused a significant reduction in the frequency of tongue carcinoma (41-91% reduction, P < 0.05) and the order of chemopreventive efficacy was curcumin > beta-carotene > hesperidin. The incidences of oral preneoplasia in rats fed the diets mixed with these compounds were also decreased (P < 0.05). There were no such lesions in rats treated with test compounds alone or those in an untreated control group. Dietary administration of these compounds significantly decreased the labeling index of bromodeoxyuridine and the number and area of silver-stained nucleolar organizer region proteins per cell nucleus that are proliferation biomarkers, of the tongue squamous epithelium (P < 0.05). In addition, polyamine levels in the oral mucosa were lowered in rats treated with 4-NQO and three test compounds when compared to those give 4-NQO alone (P < 0.05).(ABST

Topics: 4-Hydroxyaminoquinoline-1-oxide; 4-Nitroquinoline-1-oxide; Animals; beta Carotene; Carcinoma, Squamous Cell; Carotenoids; Curcumin; Hesperidin; Male; Mouth Neoplasms; Nucleolus Organizer Region; Polyamines; Precancerous Conditions; Rats; Rats, Inbred F344; Tongue; Tongue 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

A case-control study was conducted in Melbourne, Australia. Forty-one men with histologically confirmed squamous cell oral or pharyngeal cancer were compared with 398 male community controls. A statistically significant increase in risk was found for alcohol (ethanol) consumption and for smoking, and there was a synergistic effect for these two exposures. Statistically significant protection was noted with increasing intake of dietary vitamin C, dietary beta-carotene, fruit, vegetables, and dietary fiber. The mean serum levels of beta-carotene and vitamin A were statistically significantly lower when the cases were compared with another set of 88 male controls of a similar age who were hospitalized for minor surgical operations. This study confirms a causal effect of smoking and alcohol and a protective role for a high dietary intake of fruit, vegetables, cereals, and, particularly, beta-carotene- and vitamin C-containing foods.

Topics: Alcohol Drinking; beta Carotene; Carcinoma, Squamous Cell; Carotenoids; Case-Control Studies; Fruit; Humans; Male; Oropharyngeal Neoplasms; Risk Factors; Smoking; Vegetables; Vitamin A

Topics: beta Carotene; Carcinoma, Squamous Cell; Carotenoids; Cell Transformation, Neoplastic; Head and Neck Neoplasms; Humans; Immunologic Factors; Isotretinoin; Leukoplakia, Oral; Mouth Neoplasms

A case-control study was conducted in Melbourne, Australia of 88 consecutive males admitted for the surgical removal of a nonmelanocytic skin cancer (histologically confirmed basal cell carcinoma and squamous cell carcinoma) and of 88 male control patients admitted for small elective surgical procedures. In both cases and controls, previous diet, alcohol consumption, and smoking habit were investigated and serum beta-carotene and vitamin A levels were measured. A statistically significant inverse relationship was found between the risk of skin cancer and a high intake of fish (p = 0.05); vegetables in general (p < 0.001); beans, lentils, or peas (p < 0.001), carrots, silverbeet (Swiss chard), or pumpkin (p < 0.001); cruciferous vegetables (cabbage, brussel sprouts, or broccoli) (p < 0.001); and beta-carotene- and vitamin C-containing foods (p = 0.004). Cases had a lower mean serum level of beta-carotene (p < 0.001) and vitamin A (p = 0.02) than controls. The incidence of skin cancer in the study was inversely related to the level of serum beta-carotene (p < 0.0001). The correlation coefficient between dietary beta-carotene/vitamin C and serum beta-carotene was 0.22 (p = 0.04). Smoking and alcohol consumption showed no statistically significant association with the risk of nonmelanocytic skin cancer. The results were similar for both cell types. A high intake of vegetables including cruciferous vegetables, beta-carotene- and vitamin C-containing foods, and fish appears to be protective for nonmelanocytic skin cancer, and this deserves further study, as does the possible etiologic relevance of the low serum levels of beta-carotene and vitamin A.

Topics: Aged; Alcohol Drinking; beta Carotene; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Carotenoids; Case-Control Studies; Diet; Humans; Incidence; Male; Middle Aged; Skin Neoplasms; Smoking; Vitamin A

This study compares the toxic effects of the carotenoids, beta-carotene and canthaxanthin, and alpha-tocopherol (vitamin E) on human tumor cells and their normal counterparts in vitro. Seven different malignant cell lines were examined: oral carcinoma (two cell lines), breast (two cell lines), lung carcinoma (two cell lines), and malignant melanoma. The in vitro cell culture assays showed a consistent morphologic change in the affected tumor cells following treatment with carotenoid or vitamin E. A rounding of the tumor cells and eventual lifting off the tissue culture plate were observed. These changes were apparent after 1 to 5 hours of treatment depending on the tumor cell line. Associated with these observable cellular changes were quantitative reductions in proliferation (3H-thymidine proliferation) and succinic dehydrogenase activity (MTT assay). In addition, there was a noticeable change in protein expression, with an increased expression of a 70-kD protein following treatment with beta-carotene. This protein was associated with tumor cells showing a decrease in proliferation (oral carcinoma, malignant melanoma) but not with normal keratinocytes or melanocytes. These studies substantiate a selective cytotoxic effect on human tumor cell growth by carotenoids and alpha-tocopherol in vitro, and may provide an explanation of the therapeutic activity of these agents and their possible use in the treatment of premalignancy or early oral carcinoma.

Topics: beta Carotene; Breast Neoplasms; Canthaxanthin; Carcinoma, Squamous Cell; Carotenoids; Cell Division; Cells, Cultured; Electrophoresis, Polyacrylamide Gel; Humans; Keratinocytes; Lung Neoplasms; Melanocytes; Melanoma; Mouth Neoplasms; Neoplasm Proteins; Succinate Dehydrogenase; Tumor Cells, Cultured; Vitamin E

In a case-control study to determine the risk of developing lung cancer, the serum levels of vitamins A and E, carotene and selenium were determined in 31 patients, newly diagnosed as having lung cancer, and in matched controls, the said controls being selected from outpatients with no cancer. A significant, inverse association was found between serum vitamins A and E and lung cancer. The relative risk for the low vs high tertiles were, respectively, 5.94 for serum vitamin A and 8.44 for serum vitamin E. Taking histological cancer subtype into account, no relation was revealed between the microelements and squamous cell carcinoma of the lung. The relative risk for lung cancer was 6.50, however, when three, or all four, microelement levels were in the lowest tertile, compared with there being fewer than three in the lowest tertile. Even when three microelements, excluding vitamin E which had the most significant inverse association with lung cancer, were considered, the relative risk was 7.50 when any two or all three were in the lowest tertile, compared with there being just one microelement or none at all in the lowest tertile. A combined effect of vitamins A and E, carotene and selenium on the development of lung cancer has, therefore, been suggested. Further studies will thus be necessary to elucidate the cumulative effect of the serum micronutrients and trace elements, as well as the effect of single elements, on the development of lung cancer.

Topics: Adenocarcinoma; Adult; Aged; beta Carotene; Carcinoma; Carcinoma, Squamous Cell; Carotenoids; Case-Control Studies; Female; Humans; Lung Neoplasms; Male; Middle Aged; Risk Factors; Selenium; Smoking; Vitamin A; Vitamin E

Dietary levels of beta-carotene and vitamin E have been associated with cancer prevention and to a lesser extent, with therapeutic enhancement of cancer treatment. We report on the cytotoxicity of beta-carotene, vitamin E, and the combination of beta-carotene and vitamin E in human SCC-25 squamous carcinoma cells under various environmental conditions found in solid tumor masses. Beta-Carotene was selectively cytotoxic toward normally oxygenated cells and was generally more cytotoxic at normal pH than at acidic pH (6.45). Vitamin E was selectively cytotoxic toward normally oxygenated cells following 6 h exposure at normal pH and was generally equally cytotoxic toward normally oxygenated and hypoxic cells under the other conditions tested. Beta-Carotene was an effective modulator of cisplatin (CDDP) cytotoxicity toward SCC-25 cells, whereas vitamin E was not. Both beta-carotene and vitamin E were effective modulators of melphalan cytotoxicity toward SCC-25 cells. Treatment of SCC-25 cells with beta-carotene (70 microM, 2h) resulted in a reduction in superoxide dismutase activity, in glutathione-S-transferase activity, and in nonprotein sulfhydryl levels in the cells. Exposure to vitamin E or to a combination of beta-carotene and vitamin E increased the glutathione-S-transferase activity in SCC-25 cells by 40%-45% over the control value. Treatment with beta-carotene, vitamin E, or canthaxanthin reduced the incorporation of [3H]-thymidine into SCC-25 cells but not that into normal human keratinocytes. The most marked reduction in [3H]-thymidine incorporation into SCC-25 cells occurred following treatment with the combination of beta-carotene and melphalan. We hope to continue to explore the mechanisms of this effect and to study these combinations in vivo.

Topics: Alkylating Agents; Antineoplastic Agents; beta Carotene; Carcinoma, Squamous Cell; Carotenoids; Cell Hypoxia; Cell Survival; Dose-Response Relationship, Drug; Drug Interactions; Humans; Hydrogen-Ion Concentration; Melphalan; Organoplatinum Compounds; Tumor Cells, Cultured; Vitamin E

The purpose of this study was to extend the knowledge of the antitumor activity of liposomes and to identify, for the first time, the antitumor effect of liposomes with the antioxidant beta-carotene. The administration of the carotenoid encapsulated in in liposomes has the advantages of quantitation, facilitation, and most importantly an increased therapeutic response, resulting in the accentuation of regression of carcinoma in the hamster pouch. Tumors induced after the application of the carcinogen 7,12-dimethylbenz[alpha]anthracene (0.5%) were injected with liposomes composed of phosphatidylcholine, phosphatidylserine, and phosphatidylethanolamine in a ratio of 1:1:1 (large unilamellar vesicles). Tumor-bearing animals were divided into four groups, each containing 10 hamsters. The group treated with the liposomes of beta-carotene exhibited a significantly lower tumor burden (approx 5,000-fold difference) than the control tumor group. Electron- and light-micrographic analyses were used to substantiate the gross observations of tumor regression. It was noted that the carcinoma cells endocytozed liposomes in increased numbers compared with normal mucosa treated with liposomes. In addition, non-tumor-bearing hamsters injected with beta-carotene liposomes or liposomes alone did not exhibit any pathological change to the normal mucosa. An inflammatory infiltrate consisting of mononuclear cells, mast cells, and some polymorphonuclear leukocytes was noted, and degranulating polymorphonuclear leukocytes and mast cells and eosinophils predominated in the tumor controls (7,12-dimethylbenz[alpha]anthracene treated only). Notably, not all areas of degenerating dysplasia or early carcinoma exhibited a dense inflammatory response adjacent to the mucosa after the injection of beta-carotene liposomes. The results demonstrate a selective nontoxic therapy to regress experimental oral cancer.

Topics: Animals; beta Carotene; Carcinoma, Squamous Cell; Carotenoids; Cheek; Chromatography, High Pressure Liquid; Cricetinae; Drug Carriers; Liposomes; Male; Mesocricetus; Mouth Neoplasms

Human keratinocytes, obtained from bioptic specimens of healthy and preneoplastic oral mucosa, and from human cell lines from oral cavity tumors (KB and SCC-25) were treated with beta-carotene (10 microM). The colony forming efficiency (CFE), the proliferation rate and the frequency of micronucleated cells were measured in these cultures. CFE was significantly reduced (p less than 0.05) by beta-carotene treatment in cells from healthy mucosa and in KB cells. Decreases (p greater than 0.05; NS) were also observed in cells from pathological mucosa and in SCC-25 cells. Cell proliferation rate was not substantially affected by beta-carotene in all cultures. Finally, a decreased frequency of micronucleated cells was found in treated cultures, but significant reductions (p less than 0.05) were only observed in cultures from oral mucosa (healthy and pathological) as well as in KB cell cultures. Our results indicate that beta-carotene is able to reduce the clonogenic activity (CFE), even if it does not seem to influence cell proliferation, and that it has a protective effect against genotoxic damage.

Topics: Adolescent; Adult; Aged; beta Carotene; Biopsy; Carcinoma, Squamous Cell; Carotenoids; Cell Division; Cells, Cultured; Female; Humans; Keratinocytes; Male; Micronucleus Tests; Middle Aged; Mouth Neoplasms; Precancerous Conditions; Stem Cells

Several studies have correlated the excessive production of prostaglandins (PGs) with tumor promotion and the suppression of the immune response. Inhibition of PGs by pharmacological agents has been demonstrated to enhance immunocompetence, and to suppress growth of tumors in animals and humans. In this study we examined the effect of retinol (I), all-trans-retinoic acid (II), N-(4-Hydroxyphenyl) retinamide (N-4-HPR) (III), canthaxanthin (CTX) (IV), and beta-carotene (beta-CT) (V) on the bioconversion of 14C-arachidonic acid (AA) to PGE2 by squamous carcinoma cells of the tongue, SCC-25. Agents (I), (II), (III), (IV) inhibited while (V) stimulated PGE2 formation in a dose related manner. N-4-HPR was the most potent inhibitor of PGE2 synthesis. The data suggest that certain retinoids and carotenoids have the potential of inhibition of PG synthesis by oral squamous carcinoma cells. Inhibitory effects such as those described here and antioxidant properties might in part contribute to the antiinflammatory and anticarcinogenic activity of retinoids in vivo.

Topics: beta Carotene; Canthaxanthin; Carcinoma, Squamous Cell; Carotenoids; Chromatography, Thin Layer; Fenretinide; Humans; Indomethacin; Prostaglandins; Retinoids; Tongue Neoplasms; Tretinoin; Tumor Cells, Cultured; Vitamin A

The hypothesis that dietary cholesterol is positively associated with lung cancer was investigated in a 24-year cohort study of 1,878 middle-aged men who were employed in 1958 by the Western Electric Company in Chicago. The relative risk of lung cancer associated with an increment in dietary cholesterol of 500 mg/day was 1.9 (95 percent confidence interval 1.1-3.4) after adjustment for cigarettes, age, and intake of beta-carotene and fat. Results suggested that the association was specific to cholesterol from eggs. Further research is needed to understand the basis for this association.

Topics: Adenocarcinoma; Adult; beta Carotene; Carcinoma, Squamous Cell; Carotenoids; Chicago; Cholesterol, Dietary; Cohort Studies; Dietary Fats; Eggs; Follow-Up Studies; Humans; Incidence; Lung Neoplasms; Male; Middle Aged; Risk; Smoking

Dietary carotene intake during the year before diagnosis was estimated for 96 men with lung cancer, 75 men with other epithelial cancers, and 97 hospital controls. Relative to those of men in the lowest third of carotene intake (less than 1,683 micrograms/day), the smoking-adjusted odds ratios for men in the middle (1,683-2,698 micrograms/day) and upper (greater than 2,698 micrograms/day) thirds of carotene intake were 0.67 and 0.45, respectively, for lung cancer (one-sided test for trend, p = 0.048) and 0.63 and 0.65, respectively, for other epithelial cancers (one-sided test for trend p = 0.074). The protective effect of estimated dietary carotene intake was considerably stronger than was the effect of total intake of carotene-rich vegetables and fruits (grams per day), providing some evidence that the protective factor is carotene itself rather than another component of vegetables and fruits.

Topics: Aged; beta Carotene; Carcinoma, Squamous Cell; Carotenoids; Case-Control Studies; Diet; Humans; Lung Neoplasms; Male; Middle Aged; Odds Ratio; Risk Factors; Smoking; Surveys and Questionnaires; Vitamin A; Vitamin E; Zinc

In the past four years this laboratory has utilized the hamster cheek pouch tumor model to investigate the anticancer activities of antioxidants, such as beta carotene. These molecules, which have exhibited no evidence of toxicity, have been administered systemically (oral ingestion), and locally to the tumor site in the hamster cheek pouch. The results have been either the inhibition of tumor growth, or the regression of tumor. Adjacent to the degenerating tumors a dense inflammatory infiltrate was observed. Specifically, the cytokines, tumor necrosis factor alpha, and beta, have been immunohistochemically localized to the site of regressed oral carcinoma. Recently, liposomes composed of phosphaditylcholine, phosphaditylserine, and phosphodityelanolamine were combined with beta carotene and injected locally to oral squamous cell carcinoma of the hamster. The results indicated that tumor cells accumulated the liposomes and were lysed while normal mucosal cells did not demonstrate this effect. Therefore antioxidants such as beta carotene can be localized to a tumor site, without a toxic response. Future studies on the anticancer activity of the antioxidants need to focus on the cellular and molecular changes produced in the immune effectors and in the mucosal cells following administration of the antioxidants.

Topics: 9,10-Dimethyl-1,2-benzanthracene; Animals; beta Carotene; Carcinoma, Squamous Cell; Carotenoids; Cheek; Cricetinae; Drug Carriers; Immunity; Immunohistochemistry; Liposomes; Male; Mesocricetus; Mouth Neoplasms; Tumor Necrosis Factor-alpha

Beta-carotene and canthaxanthin at concentrations of 70 or 300 microM were shown to inhibit the proliferation of cultured human squamous cells (SK-MES lung carcinoma and SCC-25 oral carcinoma) in a 5 hr cell density assay. Responses were similar for both tumor cell lines, ranging from 71-84% inhibition. In contrast, equimolar concentrations of alpha-tocopherol gave only 19-36% inhibition of SCC-25, but 50-75% inhibition of SK-MES cell density. Equimolar reduced glutathione resulted in 4-15% stimulation of SCC-25 and 22-25% inhibition of SK-MES cell proliferation. With cultured normal keratinocytes, treated final cell densities did not differ significantly from those of controls. Two additional assays measuring the metabolic generation of formazan (MTT assay) and [5-3H]thymidine incorporation were in substantial agreement with the growth inhibition pattern. Thus both continuous and cyclic cellular processes are involved in the tumor-specific response. Onset of the response to beta-carotene alone or in combination with alpha-tocopherol is signalled within 1-2 hours of treatment by the appearance of a unique 70 kD heat-shock protein.

Topics: beta Carotene; Canthaxanthin; Carcinoma, Squamous Cell; Carotenoids; Cell Division; Cell Survival; Glutathione; Humans; In Vitro Techniques; Keratinocytes; Liposomes; Molecular Weight; Proteins; Skin Neoplasms; Tumor Cells, Cultured; Vitamin E

Second primary tumors constitute one of the most challenging problems in head and neck cancer. Their etiology is not yet fully understood. For this reason, we studied the relationships of vitamins A and E and beta-carotene serum levels in patients with head and neck cancer with and without second primary tumors. The results indicate lowered levels of beta-carotene in both groups of patients, while the levels of vitamin A and vitamin E were statistically significantly lower in patients with second tumors than in the group with a single head and neck cancer. This suggests that low vitamin A and vitamin E levels may play a role in the etiology of second tumors in head and neck cancer patients.

Topics: beta Carotene; Carcinoma, Squamous Cell; Carotenoids; Head and Neck Neoplasms; Humans; Neoplasms, Multiple Primary; Vitamin A; Vitamin E

Beta carotene, canthaxanthin, and a carotenoid mixture from an extract of algae were shown to prevent or inhibit the gross development of squamous cell carcinoma induced in the hamster buccal pouch by 7,12-dimethylbenz(a)anthracene. The carotenoids, dissolved in mineral oil, were administered by oral ingestion on days alternate to the carcinogen. Animals fed similar amounts of canthaxanthin, beta carotene or algae extract exhibited a statistically significant reduction in the development of tumors, both in number and size. The feeding of carotenoids, besides inhibiting gross tumor development, also produced a histologically unique picture. Microscopic areas of dysplasia, carcinoma in situ histologically unique picture. Microscopic areas of dysplasia, carcinoma in situ, or early carcinoma showed areas of tumor lysis and an inflammatory infiltrate consisting of lymphocytes and histiocytes. Characterization of this infiltrate disclosed a significant increase in cytotoxic lymphocytes, and cytotoxic macrophages producing tumor necrosis factor alpha. To confirm the presence of cytotoxic lymphocytes and macrophages a 51Cr release assay was performed. The results indicate that the immune response of the hamster was directed to the developing areas of dysplasia and carcinoma and was associated with the observations of prevention and inhibition of the growth of oral squamous cell carcinoma.

Topics: Administration, Oral; Animals; beta Carotene; Canthaxanthin; Carcinoma, Squamous Cell; Carotenoids; Cheek; Cricetinae; Cytotoxicity, Immunologic; Male; Mouth Neoplasms; T-Lymphocytes, Cytotoxic; Tumor Necrosis Factor-alpha

Regression of 7,12-dimethylbenz[a]anthracene (DMBA)-induced epidermoid carcinomas of hamster buccal pouch was accomplished by local injections of beta-carotene and canthaxanthin. One-hundred male hamsters (2-3 months old) were divided into five groups of 20 animals. All animals had the right buccal pouches painted three times weekly for 14 weeks with a 0.5% solution of DMBA in mineral oil, at which time all animals exhibited gross tumors of variable size and number. Group 1 animals were then injected locally into the right buccal pouch twice weekly for 4 weeks with 250 micrograms-carotene in 0.1 ml minimal essential medium (MEM) per injection. Group 2 animals were similarly injected with 250 micrograms canthaxanthin in 0.1 ml MEM. Group 3 animals were similarly injected with 250 micrograms 13-cis-retinoic acid in 0.1 ml MEM. Group 4 animals were injected only with MEM; Group 5 animals were untreated controls. Animals were killed in a carbon dioxide chamber, and buccal pouches were photographed. Tumors were counted and measured. Tumor burden in each group was compared, and statistical significance between groups was recorded. beta-Carotene was more effective than canthaxanthin in tumor regression. 13-cis-Retinoic acid had no effect in this system.

Topics: 9,10-Dimethyl-1,2-benzanthracene; Administration, Buccal; Animals; beta Carotene; Canthaxanthin; Carcinoma, Squamous Cell; Carotenoids; Cheek; Cricetinae; Mouth Neoplasms; Remission Induction

Topics: Adult; Age Factors; Aged; Aged, 80 and over; beta Carotene; Carcinoma, Squamous Cell; Carotenoids; China; Dose-Response Relationship, Drug; Feeding Behavior; Humans; Lung Neoplasms; Male; Middle Aged; Risk Factors; Smoking; Vitamin A

Topics: Antineoplastic Combined Chemotherapy Protocols; beta Carotene; Carcinoma, Squamous Cell; Carotenoids; Humans; Middle Aged; Mouth Mucosa; Mouth Neoplasms; Radiotherapy; Stomatitis

Beta carotene (250 micrograms/ml) dissolved in mineral oil applied either topically or injected locally (190 ng/ml dissolved in media) into DMBA (7,12-dimethylbenz(a)anthracene)-induced or HCPC-1 cell line-produced oral squamous cell carcinoma of the hamster buccal pouch was observed to result in the regression of these tumors. (p less than or equal to .005) Beta carotene application to tumor bearing pouches was observed to produce a dramatic increase in positively stained macrophages for tumor necrosis factor (TNF-alpha) as compared to macrophages in control pouches. Macrophages from hamsters with regressed tumor were shown to produce a significant increase in cytotoxicity to HCPC-1 tumor cells. Regression of the hamster oral carcinoma was correlated with the increased capacity of macrophages to lyse tumor cells, and related to the induction of tumor necrosis factor which was associated with the administration of the carotenoid, beta carotene.

Topics: 9,10-Dimethyl-1,2-benzanthracene; Administration, Topical; Animals; beta Carotene; Carcinoma, Squamous Cell; Carotenoids; Cheek; Cricetinae; Cytotoxicity, Immunologic; Glycoproteins; Macrophages; Male; Mesocricetus; Mouth Neoplasms; Neoplasm Transplantation; Tumor Necrosis Factor-alpha

We studied the relation of serum vitamin A (retinol), beta-carotene, vitamin E, and selenium to the risk of lung cancer, using serum that had been collected during a large blood-collection study performed in Washington County, Maryland, in 1974. Levels of the nutrients in serum samples from 99 persons who were subsequently found to have lung cancer (in 1975 to 1983) were compared with levels in 196 controls who were matched for age, sex, race, month of blood donation, and smoking history. A strong inverse association between serum beta-carotene and the risk of squamous-cell carcinoma of the lung was observed (relative odds, 4.30; 95 percent confidence limits, 1.38 and 13.41). Mean (+/- SD) levels of vitamin E were lower among the cases than the controls (10.5 +/- 3.2 vs. 11.9 +/- 4.90 mg per liter), when all histologic types of cancer were considered together. In addition, a linear trend in risk was found (P = 0.04), so that persons with serum levels of vitamin E in the lowest quintile had a 2.5 times higher risk of lung cancer than persons with levels in the highest quintile. These data support an association between low levels of serum vitamin E and the risk of any type of lung cancer and between low levels of serum beta-carotene and the risk of squamous-cell carcinoma of the lung.

Topics: Aged; beta Carotene; Carcinoma, Squamous Cell; Carotenoids; Humans; Lung Neoplasms; Male; Maryland; Middle Aged; Risk; Selenium; Smoking; Vitamin A; Vitamin E

Topics: beta Carotene; Canthaxanthin; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Carotenoids; Child; Child, Preschool; Drug Combinations; Drug Therapy, Combination; Etretinate; Humans; Keratosis; Male; Skin Neoplasms; Xeroderma Pigmentosum

Mice were given either beta-carotene or either of two carotenoids with no vitamin A activity--canthaxanthin or phytoene--or placebo. Skin tumors were induced in each group by each of three methods: (1) UV-B (290--320 nm); (2) dimethylbenz(a)anthracene (DMBA)/croton oil applications; (3) DMBA followed by low-dose UV-B. For tumors induced by UV-B alone, beta-carotene-phytoene- and canthaxanthin-treated mice developed fewer tumors per mouse, with a delay in tumor appearance, than did control mice. For tumors induced by DMBA/croton oil or DMBA/UV-B, mice receiving beta-carotene showed a significant difference in tumor numbers and appearance time from placebo mice; phytoene and canthaxanthin treatment had no effect.

Topics: 9,10-Dimethyl-1,2-benzanthracene; Animals; beta Carotene; Canthaxanthin; Carcinoma, Squamous Cell; Carotenoids; Croton Oil; Female; Mice; Mice, Inbred Strains; Neoplasms, Experimental; Neoplasms, Radiation-Induced; Papilloma; Skin Neoplasms; Ultraviolet Rays