ISSN:0959-8278    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

The anti-tumour and anti-cholesterol impacts of tocotrienol-rich fraction (TRF) were investigated in rats treated with the chemical carcinogen 7,12-dimethylbenz [&agr;]anthracene (DMBA), which is known to induce mammary carcinogenesis and hypercholesterolaemia. DMBA administration to rats was associated with the appearance of multiple tumours on mammary glands after 6 months. Alkaline phosphatase (ALP) and glutathione-S-transferase (GST) are used as marker enzymes to monitor the severity of carcinogenesis. Although no tumours were visible on livers, hepatic ALP and GST activities of DMBA-treated rats were profoundly elevated in comparison to enzyme activities of normal control rats. Feeding of TRF (10 mg/kg body weight/day) for 6 months, isolated from rice bran oil (RBO), to DMBA-administered rats, reduced the severity and extent of neoplastic transformation in the mammary glands. Similarly, plasma and mammary ALP activities increased during carcinogenesis (95% and 43%, respectively), were significantly decreased in TRF-treated rats, whereas TRF mediated a further increase of 51% in hepatic ALP activity. TRF treatment to rats maintained low levels of GST activities in liver (∼32%) and mammary glands (∼21%), which is consistent with anti-carcinogenic properties of TRF. Administration of DMBA also caused a significant increase of 30% in plasma total cholesterol and 111% in LDL-cholesterol levels compared with normal control levels. Feeding of TRF to rats caused a significant decline of 30% in total cholesterol and 67% in LDL-cholesterol levels compared with the DMBA-administered rats. The experimental hypercholesterolaemia caused a significant increase in enzymatic activity (23%) and protein mass (28%) of hepatic 3-hydroxy-3-methylglutaryl co-enzyme A (HMG-CoA) reductase. Consistent with TRF-mediated reduction in plasma lipid levels, enzymatic activity and protein mass of HMG-CoA reductase was significantly reduced. These results indicate that TRF has potent anti-cancer and anti-cholesterol effects in rats.

ISSN:0959-8278    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

This study intends to assess which demographic and/or clinical characteristics of lung cancer – if any – have changed during the last two decades in an Alpine area of North-West Italy. The study was carried out on 1277 consecutive lung cancer patients seen from January 1989 to October 2002 in a single institution. A set of 33 anthropometric, clinical, physical, laboratory, radiological and pathological variables was prospectively recorded for all patients. The date of diagnosis was used to divide the study population in quartiles of diagnostic age (period I: January 1989 to May 1992, 319 patients; period II: June 1992 to September 1995, 319 patients; period III: October 1995 to May 1999, 320 patients; period IV: June 1999 to October 2002, 319 patients). Patients were carefully followed up, and their subsequent clinical course recorded. The following variables showed a significant increasing trend over the years: patients' age, female sex, rate of ex-smokers, level of education, co-morbidity (both the number and the severity of previous pulmonary and extrapulmonary diseases), weight loss, liver enzymes and blood creatinine, carcinoembryonic antigen levels and the rate of adenocarcinomas. On the other hand, performance status, stage of disease, metastatic pattern, treatment modalities and survival expectancy did not change. Therefore, no diagnostic or therapeutic improvements occurring during the last 14 years had a visible impact on patients. It may be that the ‘changing face’ of lung cancer masked their effects.

ISSN:0959-8278    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

We have consistently shown that the organoselenium compound 1,4–phenylenebis(methylene)selenocyanate (p-XSC) is a superior cancer chemopreventive agent and less toxic than selenite or certain naturally-occurring selenoamino acids. To elucidate the effects ofp-XSC on human colonic mucosa, biopsies from endoscopically normal sigmoid colon of 30 patients with adenomatous polyps were incubated withp-XSC at concentrations of 1, 2 and 5 μmol/l dissolved in dimethylsulphoxide (DMSO). Biopsies incubated with DMSO or pure culture medium served as a control. Proliferating cells were labelled by bromodeoxyuridine immunohistochemistry and the labelling index (LI) was computed. Upper crypt labelling index (LI of crypt compartments 4+5) and Φh value, which are both discriminators of the expansion of the proliferative zone, were significantly lower after incubation with 1 and 5 μmol/lp-XSC, respectively (LI 4+5: 0.8 and 1.0; Φh value: 2.1 and 2.4), as compared with DMSO (LI 4+5: 3.6 and 4.5; Φh value: 7.0 and 8.3) or culture medium (LI 4+5: 3.3 and 4.5; Φh value: 7.2 and 8.1) (P<0.005 andP<0.05 by Friedman's block test). A trend towards lower levels of LI 4+5 (P=0.059) and Φh value (P=0.075) were seen after 2 μmol/lp-XSC incubation compared with DMSO. Since hyperproliferation of colonic crypt cells with expansion of the proliferative zone is regarded as a biomarker of increased cancer risk, the antiproliferative effects ofp-XSC especially on upper crypt LI and Φh value may indicate a possible protective effect of this organoselenium compound in the prevention of human colon cancer development.

ISSN:0959-8278    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

H-89 is a compound characterizedin vitroas a potent and selective inhibitor of protein kinase A. In the present study, we observed that H-89 induced morphological transformation and caused growth inhibition of the human colon cancer cell line Caco-2 in a dose-dependent manner. However, another protein kinase A inhibitor, H-8, had no effect on Caco-2 cells. To evaluate the possible molecular mechanism of H-89-evoked effects in Caco-2 cells, we analysed the capacity of H-89 to regulate the protein kinase B (Akt/PKB) signalling pathway. H-89 treatment led to an activation of Akt/PKB in Caco-2 cells. This activation was phosphatidylinositol 3 (PI3)-kinase-dependent and promoted survival of Caco-2 cells because the PI3 kinase inhibitor LY294002 inhibited the Akt/PKB activation and induced apoptosis of Caco-2 cells. To test whether Akt/PKB activity promoted resistance to H-89-induced effects, LY294002 was added in combination with H-89. LY294002 greatly potentiated the H-89-induced growth inhibition and apoptosis of Caco-2 cells. These results suggest that the H-89-induced growth inhibition of Caco-2 cells is associated with phosphorylation of Akt/PKB protein and that the cells become more sensitive to H-89 and die by apoptosis upon inhibition of the PI3K/Akt pathway.

ISSN:0959-8278    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Breast cancer incidence suggests a lifestyle cause. A lifestyle factor used near the breast is the application of antiperspirants/deodorants accompanied by axillary shaving. A previous study did not support a link with breast cancer. If these habits have a role in breast cancer development, women using antiperspirants/deodorants and shaving their underarms frequently would be expected to have an earlier age of diagnosis than those doing so less often. An earlier age of diagnosis would also be expected in those starting to use deodorants and shaving at an earlier age. This is the first study to investigate the intensity of underarm exposure in a cohort of breast cancer survivors. Four hundred and thirty-seven females diagnosed with breast cancer were surveyed. Once grouped by their frequency of underarm hygiene habits, the mean age of diagnosis was the primary end point. Secondary end points included the overall frequency of these habits, and potential usage group confounding variables were evaluated. All statistical tests were two-sided. Frequency and earlier onset of antiperspirant/deodorant usage with underarm shaving were associated with an earlier age of breast cancer diagnosis. Combined habits are likely for this earlier age of diagnosis. In conclusion, underarm shaving with antiperspirant/deodorant use may play a role in breast cancer. It is not clear which of these components are involved. Reviewed literature insinuates absorption of aluminium salts facilitated by dermal barrier disruption. Case-controlled investigations are needed before alternative underarm hygiene habits are suggested.

ISSN:0959-8278    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

The main objectives were to describe the measures taken by women to detect breast disease prior to invitation to participate in a screening programme for breast cancer, and to identify factors related to non-participation in this programme. A cross-sectional study was designed at the Breast Cancer Early Detection Program of Sabadell-Cerdanyola (BCEDP), using data collected in interviews conducted face to face or over the telephone with 13 760 women participating in the programme and 280 non-participants. A total of 74.2% of the participants versus 70.4% of the non-participants reported having taken measures to detect breast disease, and 71.7% of the participants had undergone mammography versus 69.6% of the non-participants. Of the 10 057 women who had had mammograms, 58% had done so less than 2 years previously. Factors found to be associated to non-participation in the multivariate analysis were: higher level of education, higher occupational skills or working at home, self- or gynaecological examination of breasts, and having received hormone replacement therapy. Higher age group was the only factor that increased the probability of not having undergone mammography previously. Despite the high prevalence of prior measures to detect breast cancer and the similar prevalence between participating and non-participating women, this behaviour is much less prevalent in the group of women 60 years of age or older.

ISSN:0959-8278    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

The present study was undertaken to examineCYP1A1andXRCC1polymorphisms as potential genetic susceptibility markers for laryngeal squamous cell carcinoma (SCC). Eighty-eight patients with laryngeal SCC and 178 randomly selected healthy blood donors from the same Caucasian population (Porto, Northern Portugal) were analysed forCYP1A1(MspIandNcoI) andXRCC1(Arg194Trp and Arg399Gln) polymorphisms, using PCR-RFLP techniques.CYP1A1 MspIMH (mutant homozygous) andCYP1A1 NcoIHT (heterozygous) genotypes were more frequent in patients than in controls, with those carrying aCYP1A1 NcoIHT genotype having a 2.3-fold higher risk for tumour development. On the other hand, polymorphisms inXRCC1codon 399 and codon 194 do not seem to play a role in the aetiology of smoking-related laryngeal SCC, once its distribution was similar in both analysed groups. All the significant associations observed were exclusively due to differences between controls and larynx glottic cancer patient subgroup. Furthermore, lower lifetime tobacco consumption was observed in laryngeal SCC patients carrying theMspIandNcoIpolymorphisms, than in those who did not show the polymorphic variants. This investigation seems to support the importance ofCYP1A1gene polymorphism as a potential genetic marker of laryngeal cancer development, specially concerning smokers who have inherited the at-risk genotypesCYP1A1 MspIMH orCYP1A1 NcoIHT, who do appear to be more susceptible to the development of SCC of the glottic larynx.

ISSN:0959-8278    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

The incidence of malignant melanoma and non-melanoma skin cancers has increased rapidly in Sweden as well as in other western countries during the last 20 years. Adolescents are an important group in skin cancer prevention. Interventions targeting this group have been reported to affect knowledge and attitudes, but the effect on sun protection behaviour has been slight. The aim of this study was to investigate the applicability of the Transtheoretical Model (TTM) for skin cancer prevention for adolescents. A random sample of 1200 18-year-olds living in Stockholm County was selected from the national census registry. A questionnaire that included three of the major constructs of the TTM (i.e. stages of change, processes of change and decisional balance) was sent by mail. The majority of the teenagers were in the precontemplation stage for giving up intentional tanning. The relations between the stages of change and two other major constructs of the TTM, processes of change and decisional balance, were consistent with data on other health behaviours. The results may aid in developing successful skin cancer prevention programmes. The results give support for the stages of change measurement used in this study and that utilizing the TTM in skin cancer prevention may be appropriate.

ISSN:0959-8278    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Some PCB congeners have shown oestrogenic effects, and this has raised concern that they may increase the risk of breast cancer. In this article we provide a quantitative review of the epidemiologic evidence on environmental exposure to PCBs and breast cancer risk. The vast majority of prospective and retrospective studies did not find any association between total PCB concentrations and breast cancer risk. No association was found for congeners in groups I (potentially oestrogenic) and III (biologically persistent phenobarbital-type cytochrome P450 inducers), according to the classi-fication proposed by Wolff and Toniolo, while less consistent results were reported for group II (potentially anti-oestrogenic and immunotoxic, dioxin-like). Two studies found a threefold risk of postmenopausal breast cancer for women with an A2455G base change in exon 7 of the polymorphicCYP1A1gene (a member of the cytochrome P450 family) and high PCB levels, compared with women with two wild-type alleles and low PCB, based however on very few cases. Thus, the epidemiological evidence does not support the hypothesis of an association of environmental exposure to PCBs in adulthood in the general population and risk of breast cancer, although uncertainties remain for selected subgroups of women or individual PCB congeners.

ISSN:0959-8278    

出版商:OVID    

年代:2003

数据来源: OVID