Premenopausal intakes of vitamins A, C, and E, folate, and carotenoids, and risk of breast cancer.

Intakes of vitamins A, C, and E, folate, and carotenoids have been hypothesized to reduce the risk of breast cancer. However, previous epidemiological studies on these nutrients and breast cancer risk have been inconclusive, and have included primarily postmenopausal women. We examined the intake of these nutrients in relation to breast cancer risk among 90,655 premenopausal women ages 26-46 years in 1991 in the Nurses' Health Study II. Nutrient intake was assessed with a validated food-frequency questionnaire at baseline in 1991 and in 1995. During 8 years of follow-up from 1991 to 1999, we documented 714 incident cases of invasive breast cancer. Overall, none of the vitamins and carotenoids was strongly related to a reduced risk of breast cancer. However, intake of vitamin A, including preformed vitamin A and carotenoids, was associated with a reduced risk of breast cancer among smokers; participants in the highest quintile of total vitamin A intake had a multivariate relative risk of 0.28 (95% confidence interval 0.12-0.62; P, test for trend <0.001; P, test for interaction <0.001) compared with those in the lowest quintile of intake. We found no evidence that higher intakes of vitamins C and E, and folate in early adult life reduce risk of breast cancer. However, intake of vitamin A may be related to a reduced risk of breast cancer among smokers.     

Intakes of fruits, vegetables, vitamins A, C, and E, and carotenoids and risk of renal cell cancer.

BACKGROUND: Fruits and vegetables rich in antioxidants have been proposed to reduce the risk of renal cell cancer. However, few prospective studies have examined the intakes of fruits, vegetables, and antioxidant vitamins in relation to the risk of renal cell cancer. METHODS: We prospectively examined the associations between the intakes of fruits, vegetables, vitamins A, C, and E, and carotenoids and risk of renal cell cancer in women and men. We followed 88,759 women in the Nurses' Health Study from 1980 to 2000, and 47,828 men in the Health Professionals Follow-up Study from 1986 to 2000. We assessed dietary intake every 2 to 4 years using a validated semiquantitative food frequency questionnaire. The Cox proportional hazards model was used to estimate study-specific multivariate relative risks (RR), which were pooled using a random effects model. RESULTS: A total of 248 (132 women and 116 men) incident renal cell cancer cases were ascertained during 2,316,525 person-years of follow-up. The consumption of fruits and vegetables was associated with a decreased risk of renal cell cancer in men (multivariate RR, 0.45; 95% CI, 0.25-0.81, for >or=6 servings of fruit and vegetable intake/d versus <3 servings/d; P test for trend = 0.02), but not in women (multivariate RR, 1.17; 95% CI, 0.66-2.07, for the same contrast; P test for trend = 0.25; P test for between-studies heterogeneity = 0.02). Intakes of vitamins A and C from food and carotenoids were inversely associated with the risk of renal cell cancer in men only, but we cannot exclude the possibility that this was due to other factors in fruit and vegetables. No clear association was observed for vitamin E in women or men. CONCLUSIONS: Fruit and vegetable consumption may reduce the risk of renal cell cancer in men.     

Occurrence,Efficacy, Metabolism,and Toxicity of Triclosan

Triclosan has broad-spectrum anti-microbial activity against most gram-negative and gram-positive bacteria. It is widely used in personal care products, household items, medical devices, and clinical settings. Due to its extensive use, there is potential for humans in all age groups to receive life-time exposures to triclosan, and, indeed, triclosan has been detected in human tissues and the environment. Data gaps exist regarding the chronic dermal toxicity and carcinogenicity of triclosan, which is needed for the risk assessment of triclosan. The US Food and Drug Administration (FDA) nominated triclosan to the National Toxicology Program (NTP) for toxicological evaluations. Currently, the NTP is conducting several dermal toxicological studies to determine the carcinogenic potential of triclosan, evaluate its endocrine and developmental-reproductive effects, and investigate the potential UV-induced dermal formation of chlorinated phenols and dioxins of triclosan. This paper reviews data on the human exposure, environmental fate, efficacy of anti-microbial activity, absorption, distribution, metabolism and elimination, endocrine disrupting effects, and toxicity of triclosan.     

Tobacco, alcohol, diet, occupation, and carcinoma of the esophagus

Information on occupation, smoking, food and beverage consumption, and medical history were compared between 275 incident cases of carcinoma of the esophagus and 275 neighborhood controls who were matched to the cases on age (within 5 years), race, and sex. Tobacco use, mainly cigarette smoking, was a significant risk factor for carcinoma of the esophagus. Ex-smokers of cigarettes showed a reduced risk relative to those who continued to smoke, and current smokers of two or more packs per day displayed a higher risk than those who smoked less. Alcohol consumption was another significant risk factor for carcinoma of the esophagus; there was a highly significant trend with average daily dose of ethanol. Relative to controls, cases also consumed significantly more fried bacon or ham, less fresh fruits and raw vegetables, and were more likely to prefer white than whole grain bread. Finally, there was a significant association between carcinoma of the esophagus and long-term occupational exposure to metal dust; this association was largely confined to the lower one-third section of the esophagus.     

Fat, fiber, fruits, vegetables, and risk of colorectal adenomas

A case-control study was conducted at the National Naval Medical Center (Maryland, USA) from 1994 to 1996 to investigate the possible association between dietary factors and colorectal adenomas. Cases (n = 239) were subjects diagnosed with adenomas (146 new and 93 recurrent) by sigmoidoscopy or colonoscopy. Those with no evidence of adenomas found by sigmoidoscopy were recruited as controls (n = 228). Dietary variables, assessed by a 100-item food frequency questionnaire, were analyzed by the logistic regression model, which was adjusted for age, gender and total energy intake. Variables of fat intake were further adjusted for red meat intake. An increased risk of 7% [odds ratio (OR): 1.07; 95% confidence interval (95% CI): 0.94-1.22] per 5% energy/day from total fat was observed. Every additional 5% unit of oleic acid intake/day significantly increased the adenoma risk by 115% (OR: 2.15; 95% CI: 1.05-4.39). Red meat fat increased the risk by 20% (OR: 1.20; 95% CI: 0.71-2.04), and white meat fat decreased the risk by 67% (OR: 0.33; 95% CI: 0.19-0.95) for every additional 5% unit of respective intake/day. Risk decreased by 41% (OR: 0.59; 95% CI: 0.41-0.86) for every additional 5% unit of fiber intake/day. Vegetable [OR per 100 g of vegetable intake/day: 0.83, 95% CI: 0.67-1.04] and fruit (OR per 100 g of fruit intake/day: 0.92, 95% CI: 0.82-1.03) intake showed an inverse association, and the results are suggestive of an association with the risk for adenomas. In conclusion, a strong positive association between oleic acid intake and colorectal adenoma risk was observed. This is likely to be an indicator of "unhealthy" food (meat, dairy, margarine, mayonnaise, sweet baked food) consumption in this population. Increased intake of dietary fiber was associated with a moderately decreased risk of adenomas.     

Age,Race, Sex,Stage, and Incidence of Cutaneous Lymphoma

BackgroundThe incidence of the T- and B-cell CLs has been well documented, but information pertaining to racial incidence by age, and by burden of disease (stage) have not been extensively documented.Materials and MethodsThe SEER 2004-2008 public use database was investigated. The relative incidence of CL in different races and age groups was examined. Univariate and multivariate stepwise logistic regression was performed for the likelihood of presenting at a higher stage.ResultsOf 4496 patients diagnosed with CL between 2004 and 2008; 1713 patients were diagnosed with MF, 1518 with non-MF cutaneous T-cell lymphoma, and 1265 patients with cutaneous B-cell lymphoma. For MF, there was a trend for females to be less likely to present with a higher T-stage (T3-T4) than males (odds ratio [OR], 0.73) on multivariate analysis (P = .06). For race, AA had a significantly increased risk of presenting with higher T-stage (T3-T4) MF (OR, 1.72) on multivariate analysis (P = .02), compared with white patients. For white, AA, Asian/Pacific Islander, and Native American/other/unknown, the mean age at diagnosis was 59.2, 51.5, 51.3, and 53.8. These groups presented at a significantly different age than white (P = .0001, 0.0001, and 0.0006).ConclusionNonwhite racial groups present with MF at an earlier age compared with white, and AA have increased risk of presenting with higher T-stage compared with white. These findings have significant implications regarding need for earlier diagnosis and understanding the reasons for racial disparity in age and stage of presentation.     

Antitumor activity of halogen analogs of phosphoramide,isophosphoramide, and triphosphoramide mustards,the cytotoxic metabolites of cyclophosphamide,ifosfamide, and trofosfamide

A series of halogen analogs of phosphoramide mustard, isophosphoramide mustard, and triphosphoramide mustard, the cytotoxic metabolites of the antitumor drugs cyclophosphamide, ifosfamide, and trofosfamide, respectively, was evaluated in vitro against human tumor cell lines and in vivo against experimental tumors to investigate the effect of replacement of chlorine with bromine or fluorine on the antitumor activity of the parent phosphoramide mustards. In the experimental tumors L1210 leukemia, B16 melanoma, mammary adenocarcinoma 16/C, and ovarian sarcoma M5076, the antitumor activity of the analogs was observed to be generally comparable with that of the parent mustards when chlorine was replaced by bromine but uniformly lower when chlorine was replaced by fluorine. Furthermore, the monobromo analog of isophosphoramide mustard displayed equal or somewhat greater activity in comparison with cyclophosphamide when evaluated against subcutaneously implanted L1210 leukemia with intraperitoneal drug treatment and against mammary adenocarcinoma 16/C.This work was financially supported by NIH, NCI grant PO1 CA34200     

Consumption of alcohol,coffee, and tobacco,and gastric cancer in Spain

A case-control study on gastric cancer was carried out between 1987 and 1989 in four regions of Spain. Three hundred and fifty-four cases of histologically confirmed adenocarcinoma were included (235 men and 119 women). For each case, a control was selected, matched by sex, age, and area of residence, from the same hospital as the case. No association was observed with smoking, nor with the consumption of coffee or tea. The usual consumption of alcohol was associated with gastric cancer in men (odds ratio = 1.54, 95 percent confidence interval = 1.03–2.31), but there was no dose-response relationship. No association was observed in women. All estimations were carried out taking into account the effect of the dietary factors associated with gastric cancer. In accordance with previous evidence, the association observed between gastric cancer and alcohol appears not to be causal.Drs Agudo and González are with the Unit of Epidemiology, Hospital de Mataró, Mataró, Spain. Dr Marcos is with the Department of Preventive Medicine, Hospital Clínico, Zaragoza, Spain. Dr Sanz is with the Department of Pathology, Hospital del INSALUD, Soria, Spain. Dr Saigi is with the Department of Oncology, Hospital General de Granollers, Granollers, Spain. Dr Verge is with the Department of Surgery, Hospital de Terrassa, Terrassa, Spain. Dr Boleda is with the Department of Oncology, Hospital S. Camil, Sant Pere de Riba, Sapin. Dr Ortego is with the Department of Pathology, Hospital Clínico, Zaragoza, Spain. Address correspondence to Dr Agudo, Unit of Epidemiology, Hospital de Mataró, c. Hospital 31, 08301 Mataró, Spain. This study received financial support from the Health Research Fund (FIS) of the Spanish Ministry of Health (Financial Aid for Research exp. 87/1703, exp. 89/0018 and exp. 89/0743) and from the International Agency for Research on Cancer (Collaborative Research Agreement AEP/88/02).     

Action Mechanisms of Cell-Division-Arresting Benzimidazoles and of Sterol Biosynthesis-Inhibiting Imidazoles, 1, 2, 4-Triazoles, and Pyrimidines

Summary: In spite of a formal similarity between benzimidazoles and azoles, two completely different action mechanisms are in operation, namely inhibition of tubuline association by the benzimidazoles, and inhibition of ergosterol biosynthesis at the stage of C₁₄ demethylation by imidazoles, 1, 2, 4-triazoles, and pyrimidines.
Zusammenfassung: Trotz formaler Ähnlichkeit zwischen Benzimidazolen und Azolen werden zwei vöüig verschiedene Wirkungsmechanismen verwirklicht, nämlich Hemmung der Tubulinassoziation durch Benzimidazole und Hemmung der Ergosterolbiosynthese auf der Stufe der C₁₄-Desmethylierung durch Imidazole, 1, 2, 4-Triazole und Pyrimidine.     

Cancer incidence, mortality, and associated risk factors among Asian Americans of Chinese, Filipino, Vietnamese, Korean, and Japanese ethnicities

Many studies demonstrate that cancer incidence and mortality patterns among Asian Americans are heterogeneous, but national statistics on cancer for Asian ethnic groups are not routinely available. This article summarizes data on cancer incidence, mortality, risk factors, and screening for 5 of the largest Asian American ethnic groups in California. California has the largest Asian American population of any state and makes special efforts to collect health information for ethnic minority populations. We restricted our analysis to the 4 most common cancers (prostate, breast, lung, colon/rectum) and for the 3 sites known to be more common in Asian Americans (stomach, liver, cervix). Cancer incidence and mortality were summarized for 5 Asian American ethnic groups in California in order of population size (Chinese, Filipino, Vietnamese, Korean, and Japanese). Chinese Americans had among the lowest incidence and death rate from all cancer combined; however, Chinese women had the highest lung cancer death rate. Filipinos had the highest incidence and death rate from prostate cancer and the highest death rate from female breast cancer. Vietnamese had among the highest incidence and death rates from liver, lung, and cervical cancer. Korean men and women had by far the highest incidence and mortality rates from stomach cancer. Japanese experienced the highest incidence and death rates from colorectal cancer and among the highest death rates from breast and prostate cancer. Variations in cancer risk factors were also observed and were for the most part consistent with variations in cancer incidence and mortality. Differences in cancer burden among Asian American ethnic groups should be considered in the clinical setting and in cancer control planning.     

A comparison of general,genitourinary, bowel,and sexual quality of life among long term survivors of prostate,bladder, colorectal,and lung cancer

ObjectivesStudies of local stage prostate cancer survivors suggest that treatments carry risk of persistent impotence, incontinence, and bowel dysfunction. To examine impacts of cancer type and side effects on health-related quality of life (HRQoL) in long-term cancer survivorship, we evaluated 5-year follow-up of patients with prostate cancer and compared results with a matched group of male long-term survivors of other local-stage cancers.Materials and MethodsWe examined genitourinary, bowel and sexual symptoms, and general quality of life. Matched survivors of colorectal, lung, and bladder cancers were recruited via registries in 3 different regions in the United States. Patients were surveyed 3–5 years after diagnosis with the SF-12 and EPIC to evaluate general mental and physical health-related quality of life (HRQoL) and patient function and bother.ResultsWe analyzed responses from long-term prostate (n = 77) and bladder, colorectal, and lung cancer (n = 124) patients. In multivariate analysis, long-term local stage prostate cancer survivors had significantly higher SF-12 physical component scores but did not differ from long-term survivors of other cancers in terms of their SF-12 mental summary scores. Prostate survivors had similar mental, urinary, bowel, and sexual HRQoL compared to long-term survivors of other local stage cancers.ConclusionLong-term general and prostate-specific HRQoL was similar between local stage prostate and bladder, colorectal, and lung patients with cancer. Future research focusing on factors other than initial treatment and the cancer type per se may provide more meaningful information regarding factors that predict disparities on HRQoL among longer-term survivors of early stage male cancers.     

Photoreaction,Phototoxicity, and Photocarcinogenicity of Retinoids

Abstract

Sunlight is a human carcinogen. Many retinoid-containing cosmetics are used to protect damages caused by sunlight irradiation. Since retinol is thermally unstable and retinyl palmitate (RP) is relatively more stable, RP is also widely used as an ingredient in cosmetic formulations. In general, little is known about the photodecomposition of retinoids and the toxicity of retinoids and their photodecomposition products on the skin's responses to sunlight. This review focuses on the update information on photoreactions, phototoxicity, and photocarcinogenicity of the natural retinoids including retinol, retinal, retinoid acid (RA), retinyl acetate, and RP.     

Etoposide, dexamethasone, cytarabine, and cisplatin in vincristine, doxorubicin, and dexamethasone-refractory myeloma

Based on remarkable activity in refractory lymphomas, a combination of etoposide, cisplatin (both administered by 4-day continuous infusions), cytarabine (Ara-C), and dexamethasone (EDAP) was evaluated in 20 patients with advanced myeloma refractory to standard melphalan and prednisone (MP) and/or vincristine, Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH), and dexamethasone (VAD) and even to high doses of melphalan (HDM) (seven patients). Forty percent of patients responded regardless of previously recognized risk factors (eg, duration of drug resistance, tumor mass, and serum lactic dehydrogenase [LDH] level). While the median survival was only 4.5 months, patients with good performance (Zubrod less than 2) and low or intermediate tumor stage survived more than 14 months compared with only 2 months for the remaining group. EDAP could be readily administered in the outpatient clinic, but neutropenic fever prompted hospital admission in 80% of patients, half of whom developed penumonia and sepsis, a fatal outcome in four patients. Severe myelosuppression was of short duration, so that subsequent cycles could be administered every 3 to 4 weeks. No serious extramedullary toxicity, including renal toxicity, was encountered. Marrow toxicity and hence infectious complications may be reduced by elimination of Ara-C without compromising treatment efficacy. We conclude that the lack of cross-resistance with VAD and even HDM makes EDAP or a similar combination an attractive regiment to be formally explored in an alternating sequence with VAD in high-risk myeloma.     

Antibacterial, antifungal, and anticancer activities of volatile oils and extracts from stems, leaves, and flowers of Eucalyptus sideroxylon and Eucalyptus torquata

Eucalyptus species leaves have been traditionally used to heal wounds and fungal infections. Essential oils and extracts of some Eucalyptus species possess antimicrobial and antitumor properties. We sought to determine antimicrobial and cytotoxic activities of oils and extracts of leaves, stems, and flowers of Eucalyptus sideroxylon and Eucalyptus torquata grown in Egypt. An agar diffusion method was used to analyze antimicrobial activities of essential oils and extracts of Eucalyptus against medically important gram-positive and gram-negative bacteria. A sulphorhodamine B assay was used to analyze the in vitro cytotoxic activities of oils and extracts against Human hepatocellular carcinoma cell line (HEPG2), and Human breast adenocarcinoma cell line (MCF7). Gram-positive bacteria were highly susceptible to oils and extracts of both Eucalyptus species. With the exception of Escherichia coli, gram-negative bacteria were resistant to extracts, but susceptible to the oil obtained from at least one organ of E sideroxylon and E torquata. Although Aspergillus flavus and Aspergillus niger were resistant to the extracts, essential oils of E sideroxylon and E torquata generally exhibited moderate to high antifungal activities against Candida albicans, A flavus and A niger. Oils of E torquata stems exhibited cytotoxic activities on MCF7 cells followed by oils of E torquata leaves and E sideroxylon leaves. However, oils from both species failed to exert cytotoxic effects on HEPG2 cells. This is the first report of antimicrobial and antitumor properties of E sideroxylon and E torquata. Results suggest a wider use of Eucalyptus species products in pharmaceutical, cosmetic, and food preparations.     

Pharmacokinetic and toxicity scaling of the antitumor agents amsacrine and CI-921, a new analogue, in mice, rats, rabbits, dogs, and humans

The aim was to investigate interspecies relationships between body weight (W) (kg) and various pharmacokinetic parameters for the anti-tumor agents amsacrine and its 4-methyl-5-(N-methylcarboxamide) analogue, CI-921, and examine which pharmacokinetic parameter, if any, might be used to predict the toxicity of these agents. Pharmacokinetic, plasma protein binding, and toxicity data were available for CI-921 in mice, rats, rabbits, dogs, and humans. For amsacrine, similar interspecies pharmacokinetic data were available but toxicity and protein-binding data were available for only 3 species. Significant linear relationships were obtained for CI-921 between log W and log Vss (liters) (r = 0.971, P = 0.006), and log W and log Cl (liters/h) (r = 0.911, P = 0.031) resulting in the allometric equations Vss = 1.22W0.68 and Cl = 0.91W0.51. For amsacrine these corresponding equations were Vss = 3.37W0.81 (r = 0.996, P less than 0.001), and Cl = 2.28W0.46 (r = 0.952, P = 0.012). When interspecies differences in plasma protein binding were taken into account, the allometric relationships improved and the exponents of the power equations increased. For CI-921 the allometric equations for the kinetic parameters calculated from plasma "free" concentrations were: Vssfu (liters) = 247W0.93 (r = 0.984, P = 0.002) and Clu (liters/h) = 186W0.76 (r = 0.961, P = 0.009). The dog was a noticeable outlier in the relationship between the log maximum tolerated dose (MTD) (mg/kg) of CI-921 and log W. Omission of the latter resulted in a highly significant allometric relationship, MTD = 23.6W-0.14 (r = -0.988, P = 0.012). For amsacrine there was no significant allometric relationship between MTD and W. CI-921s prolonged t1/2 in the dog and the dog's increased susceptibility to CI-921 toxicity suggested a relationship between MTD and t1/2 (h). A significant linear relationship was observed between in MTD and t1/2 (r = -0.994, P less than 0.001), from which the following equation was developed MTD = 47.5e-0.51t1/2 Combining the amsacrine toxicity data in the latter relationship yielded a similar equation MTD = 44.7e-0.51t1/2 (r = -0.933, P less than 0.0001). It was concluded that allometric equations may be developed for CI-921 and amsacrine from animal pharmacokinetic data which allow a reasonable prediction of Cl and Vss in patients, despite these agents being eliminated mainly by biotransformation. However, similar relationships between toxicity and body weight were susceptible to variation between individual species. Species differences in the toxicity of these agents were predictable from the t1/2. This study emphasized the importance of pharmacokinetic data in preclinical toxicity and efficacy testing of antitumor agents.     

Expression of blood group antigens A, B, H, Lewis-a, and Lewis-b in fetal, normal, and malignant tissues of the uterine endometrium

Fetal, normal adult, and malignant tissues of the uterine endometrium were examined by immunoperoxidase staining for the blood group antigens (BGA) A, B, H, Lewis-a, and Lewis-b. Antigens A, B, and H compatible with the ABO status of fetuses were detected in 20 of the 22 fetal tissues that were examined. Lewis-b immunoreactivity was also found in 21 fetuses, and Lewis-a was present in a third of the cases. In adult endometrium the expression of BGA H and Lewis-b was considerably lower than in fetal tissues. Malignant endometrial glands extensively reexpressed H and Lewis-b regardless of ABO status. BGA A and B were neither absent nor accumulated in cancer tissues. Thus, H and Lewis-b can be considered as oncofetal antigens since they were frequently expressed in fetal and cancer tissues, but not in normal adult tissues. The increased expression of Lewis-a antigen might be associated with malignant transformation as it was observed only in malignant tissues. However, the functional significance of alterations in BGA expression that may be associated with oncogenesis remains to be investigated.