ISSN:0959-8278    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

In vitro, for animal cells generally, butyrate at millimolar concentrations is an inhibitor of growth. In vivo, however, colonocytes are able to grow in the environment of about 20 mM butyrate produced by bacterial fermentation on the luminal side of the colonic epithelium. Anin vivoincrease of the butyrate supply results in growth stimulation of cells in the colonic crypts. This discrepancy, namely, that in cell cultures butyrate is an inhibitor of growth, whereasin vivoit has a trophic effect, is the so called in vivo paradox of butyrate. In the present review it is pointed out that butyrate is an inhibitor of histone deacetylases and there is sufficient evidence for hyperacetylation being the mechanism of thein vitrogrowth-inhibiting effect of butyrate. As within animal cells hyperacetylation has to occur at a certain butyrate concentration (1–10 mM), it is postulated that the in vivo lack of inhibition and 'paradoxical' stimulation of growth is a result of a low intracellular steady state concentration of butyrate in the lower layers of the crypt in spite of the much higher butyrate concentration on the luminal side. As butyrate is the preferential source of energy for colonocytes, thein vivotrophic effect is not paradoxical, when in spite of an increase of the butyrate concentration in stool, the intracellular butyrate concentration of intestinal epithelial cells still remains below the inhibiting level. For mature non-dividing colonocytes which are programmed for apoptosis, there is no difference between the observations madein vitroor in vivo. Furthermore, recent developments are discussed which suggest that cyclo-oxygenase-2 may play an essential role in colonic carcinogenesis. Cyclo-oxygenase- 2 is found to be expressed in most colorectal carcinomas, but not in normal non-transformed intestinal epithelial cells (DeWitt and Smith, 1995). Cyclo-oxygenase-2 overexpression makes intestinal epithelial cells resistant to butyrate-induced apoptosis (Tsujii and DuBois, 1995). This escape from butyrate-induced apoptosis appears to be an essential prerequisite for the development of colorectal cancer and suggests a functional role of butyrate in growth, differentiation and programmed cell death of colonic epithelial cells.

ISSN:0959-8278    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

The hypoxanthine/xanthine oxidase enzyme system is known to produce the superoxide ion and hydrogen peroxide during the hydroxylation of hypoxanthine via xanthine to uric acid. When chelated iron is included in this system, superoxide reduces iron(III) to iron(II) and the iron(II)-chelate further reacts with hydrogen peroxide to form the highly reactive hydroxyl radical. Because of the limitations of colourimetric and spectrophotometric techniques by which, to date, the mechanisms of hydroxyl radical formation in the hypoxanthine/xanthine oxidase system have been monitored, a high performance liquid chromatography method utilizing the ion-pair reagent tetrabutylammonium hydroxide and salicylic acid as an aromatic probe for quantification of hydroxyl radical formation was set up. In the hypoxanthine/xanthine oxidase system the major products of hydroxyl radical attack on salicylic acid were 2,5-dihydroxy benzoic acid and 2,3- dihydroxy benzoic acid in the approximate ratio of 5:1. That the hydroxyl radical is involved in the hydroxylation of salicylic acid in this system was demonstrated by the potency especially of dimethyl sulphoxide, butanol and ethanol as scavengers. Phytic acid, which is considered to be an important protective dietary constituent against colorectal cancer, inhibited hydroxylation of salicylic acid at a concentration one order of magnitude lower than the classical scavengers, but was only effective in the absence of EDTA. The method has been applied to the study of free radical generation in faeces, and preliminary results indicate that the faecal flora are able to produce reactive oxygen species in abundance.

ISSN:0959-8278    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

The relationship between the risk of biliary tract cancers and menstrual and reproductive factors has been studied in a case-control study conducted in Milan, northern Italy, between January 1984 and February 1993 on 31 incident, histologically confirmed cases and 377 controls in hospital for acute, non-neoplastic, non-gynaecological, non-hormone-related conditions. Odds ratios (ORs) together with their corresponding 95% confidence intervals (CIs) and the significance of the linear trends in risk were estimated by unconditional multiple logistic regression, after adjustment for age and cholelithiasis. Menopause was associated with a decreased risk of biliary tract cancers (OR 0.2), while late menopause and the use of hormone replacement therapy tended to increase the risk (ORs 1.8 and 2.2 respectively). Age at menarche and regular menstrual cycles were not associated. A trend in risk was found with parity, while total abortions and age at first and last birth were not related. Thus, the protective effect of early menopause and the apparent association of multiple full-term pregnancies suggest a role of female hormones in the aetiology of biliary tract cancers.

ISSN:0959-8278    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

Following examination of the geographical pattern of stomach cancer incidence in Spain, the possible relationship between diet and stomach cancer has been assessed using an ecological model which looks into the relationship between the consumption of different foods and the nutrient intake in each of the 50 Spanish provinces during the period 1964—65, and the mortality rate for stomach cancer in these same 50 provinces during a period 20 years later (1984—86). The geographical pattern of stomach cancer mortality has been arrived at using the standardized mortality ratios (SMRs) calculated for each province. The per capita consumption of foods was obtained from the National Institute for Statistics and the calculation of nutrient intake was based on tables of nutritional composition. The results have been obtained using the statistical techniques of linear and Poisson regression. Stomach cancer mortality in Spain exhibits a stable and welldefined pattern, with less risk being apparent in the Mediterranean coastal provinces. The variability in the geographical distribution of stomach cancer mortality can, in large part (76%), be explained by the variation in the types of foods consumed between provinces, and this figure rises to 82% when one considers other socio-economic variables. A significant inverse association has been found between gastric cancer mortality and consumption of vegetables, fruits and vegetable oil as well as with vegetative growth and population density. From the multiple regression analysis, which considered both nutritional and socioeconomic variables, the strongest inverse association with stomach cancer mortality was found in the consumption of green vegetables. The estimated relative risk (RR) of dying, for an increase in consumption of vegetables of 100 gper capitaper day is 0.72, (95% CI: 0.53—0.91). These results are consistent with those of similar studies elsewhere.

ISSN:0959-8278    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

The relationship between oral contraceptives (OC), menopausal hormone replacement treatment (HRT) and breast cancer risk was analysed in a case—control study conducted in the Swiss canton of Vaud on 230 cases below the age of 75, linked with the Vaud cancer registry, and 507 controls in hospital for a wide spectrum of acute, non-neoplastic, non-hormone-related diseases. A total of 77 (37.4%) cases and 134 (31.6%) of controls below the age of 70 had ever used OC, corresponding to a multivariate odds ratio (OR) of 1.5, of borderline significance. The risk was related to duration of use, but this might be partly due to a recency effect. In fact, with reference to time since last OC use, the OR was above unity for up to 14 years, but declined to 1.0 for women who had stopped OC use for ≥ 15 years. With reference to HRT, ever users were 64 (27.8%) of cases and 113 (23.3%) of controls, yielding a multivariate OR of 1.3. Also, for HRT the association was stronger for shorter time since last use; the OR was 1.5 for women who had stopped for<10 years, but declined to 0.8 for those who had stopped for 10 years or longer. The association with HRT was stronger for women aged ≥ 65. Thus, the present study confirms that breast cancer risk is moderately related to OC and HRT. The association, however, is essentially restricted to the 10—15 years after stopping use. This pattern of risk is consistent with a late-stage effect of steroid hormone preparations on the process of breast carcinogenesis, and has relevant implications for any risk/benefit assessment and public health evaluation.

ISSN:0959-8278    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

The two main determinants of oral and oesophageal cancer in Europe are alcohol and tobacco, and the two cancer sites show several similarities in their descriptive epidemiology. This study compares mortality from cancers of the oral cavity and oesophagus in European countries to evaluate similarities and differences. From official death certification numbers and population estimates, we obtained age-standardized rates for all ages and truncated (35—64 years). In most countries, rates for men tended to increase between 1955—59 and 1990—92 for both sites, although the increases were more marked for oral cancer. In the UK and Ireland, however, oral cancer decreased and oesophageal cancer increased, while in Finland and Iceland mortality for both sites decreased. The most striking increases were in Hungary, where the truncated rate in most recent calendar periods reached the highest levels in Europe. In France, rates for both cancers were extremely high: oral cancer increased from 1955—59 to the early 1980s, but started to decline afterwards. Mortality rates were much lower for women than men, and the correlation between the two sites was less marked. An age, period and cohort model, applied to the rates for men in selected European countries, suggested strong cohort effects for both cancers, generally more marked for oral cancer, with substantial increases in the cohorts born after 1920. The mortality rates of cancers of the oral cavity and oesophagus show several analogies, as expected from their relation to tobacco and alcohol; but some discrepancies suggest that other, less well-identified, factors may also influence their rates and trends in Europe.

ISSN:0959-8278    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

We have assessed the agreement of radiologists who quantitatively estimated the extent of various mammographic features of the breast. These features are of potential relevance to the estimation of the future risk of developing breast cancer. After preparation, in which various mammographic appearances and their classification were discussed and agreed upon, two radiologists, experienced in mammography, independently estimated the extent of various types of radiological density in 120 sets of mammograms, each comprised of two mediolateral and two craniocaudal views. The results showed a high level of agreement between the two radiologists in the classification of total mammographic densities (r=0.89). For classification of specific types of density, agreement was best for homogeneous densities (r=0.79), more intermediate for nodular densities (r=0.71) and worst for linear densities (r=0.48). These results show that radiologists can, with suitable preparation, identify total breast density, a mammographic sign relevant to a woman's risk of later developing breast cancer, with a high degree of agreement.

ISSN:0959-8278    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

Previous histochemical studies have shown that changes occur in the composition of mucins both in preneoplastic and neoplastic lesions of the gastric mucosa. Since monoclonal antibodies are now available which recognize the protein product of distinct mucin genes, they are likely to provide useful tools for evaluating these changes. Thus, a monoclonal antibody 996/1 raised against a peptide epitope of the colonic mucin MUC2 was examined for its potential as a prognostic indicator in gastric cancer. 996/1 works well on formalinfixed paraffin sections and shows good staining of the colonic goblet cells in the region of the golgi, while there is no staining of normal control gastric mucosa. The epitope was detected in all cases of intestinal metaplasia (44 samples) and some but not all cases of dysplasia (26 samples) and gastric carcinoma (74 samples). There was no significant difference between the positivity of the tumours according to their classification, stage and lymph node status. These results unfortunately gave little indication that this antibody would be a useful prognostic tool in gastric cancer. However, the pattern of 996/1 staining provides useful information about the molecular changes in mucin expression that occur in gastric carcinogenesis.

ISSN:0959-8278    

出版商:OVID    

年代:1996

数据来源: OVID

ISSN:0959-8278    

出版商:OVID    

年代:1996

数据来源: OVID