International journal of cancer. Supplement = Journal international du cancer. Supplement最新文献

The current epidemiological transition in less developed countries is resulting in an epidemic of chronic diseases, with cancer being the second most common cause of mortality. The evidence linking diet to the development of cancer is based largely on epidemiological analysis of the relationships of the frequency of different cancers to data on food consumption. Cohort results have made clearer the link between diet and cancer, as have data on a number of biological mechanisms. Based on the available data, recommendations on dietary practices that may prevent cancer have been published recently by the American Institute for Cancer Research and the World Cancer Research Fund. Key recommendations are: diet should be based on plant products; 400 g of vegetables and fruits, to provide more than 10% of energy, should be consumed daily; cereals, legumes and tubers should provide at least 50% of energy, and sugars less than 10%; no more than 80 g of meat should be consumed, preferably fish or poultry, and limited amounts that are cured or smoked; fat intake should be limited to no more than 30% of energy, with a predominance of monounsaturated and polyunsaturated forms; total salt consumption should be less than 6 g; perishable foods should be kept frozen or refrigerated and consumed promptly; foods should be cooked at low temperatures, better to be boiled or steamed rather than fried or grilled; alcohol should not exceed 2 drinks a day. In addition to these dietary guidelines, cancer prevention may be achieved by not smoking, by avoiding excess weight, and by increasing physical activity, including half an hour of exercise and 4 hr not resting in a chair or bed.

The results of the treatment of acute lymphoblastic leukemia (ALL) in children depend not only on the biologic diversity of the leukemia cell, the multi-drug treatment schedule and the individual variability of drug metabolism, but also on the socioeconomic and cultural background of the leukemic child. Social and cultural disparity is very marked in underdeveloped countries and has been increasing in industrialized nations. The prognostic influences of these factors are poorly documented and sometimes mistakenly attributed to differences in ethnic origin. We have investigated in Brazil the relative impact of malnutrition and socioeconomic status on the outcome of ALL, adjusting for the known influence of biologic factors. Children with ALL (n = 167) treated with a Berlin-Frankfurt-Munster-based protocol were studied prospectively. At a median follow-up of 1623 days, the estimated probability of disease-free survival was 43 +/- 4%. The main cause for interruption of remission was bone-marrow relapse. Socioeconomic indicators of poverty (poor housing conditions, low per capita income and energy consumption) were significantly associated with a greater risk of relapse in univariate analysis. They were consolidated in a single index, socioeconomic status (SES), defined by the product of monthly per capita income times mean familial daily energy consumption. Other unfavorable findings included age, z score for the height for age at diagnosis (HAZ) below-1.28 and the z score for weight for age below-1.28. After adjustment in Cox's multivariate model, only HAZ and poor SES remained as predictive factors for relapse. Poor prognosis for leukemic children of low SES is just another indicator of social inequality.

To assess the association between infant feeding and childhood cancer, a qualitative review of 9 published case-control studies was undertaken. The results of this synthesis suggest that children who are never breast-fed or are breast-fed short-term have a higher risk than those breast-fed for > or = 6 months of developing Hodgkin's disease (HD), but not non-Hodgkin's lymphoma or acute lymphoblastic leukemia. HD has features of a complex cellular immune disorder and of chronic infection. Human milk contains an extensive array of anti-microbial activity and appears to stimulate early development of the infant immune system. Artificially fed infants negotiate exposure to infectious agents without the benefits of this immunologic armament and do not do as well as breast-fed infants in resisting infection. Thus, human milk may make the breast-fed infant better able to negotiate future carcinogenic insults by modulating the interaction between infectious agents and the developing infant immune system or by directly affecting the long-term development of the infant immune system. Further research should attempt to confirm the association between infant feeding and HD in large, population-based, case-control studies. Improved measurement of infant feeding must be addressed if future studies are to advance our understanding of this association. In addition, studies of specific measures of immunity, particularly of cellular immune responses, should be conducted in populations of breast-fed and non-breast-fed young children.

Most cancers in children are acute diseases. Therefore, the incidence of malnutrition, in general, is not different from the incidence in the referral population. Some specific tumors, such as neuroblastoma and those resulting in the diencephalic syndrome, can be exceptions. By contrast, malnutrition is a frequent problem during modern intensive cancer treatment as the result of the associated anorexia, altered taste sensations and catabolic effects of drugs. In addition, there are psychogenic factors and metabolic consequences associated with the tumor itself. Nutritional support does improve the feeling of well-being and performance status, while maintaining or improving the immune competence, thereby potentially affecting survival by limiting infectious episodes. There is no convincing evidence to date that nutritional support has an antineoplastic effect per se, but deficiency of a specific nutrient might be beneficial because of a differential requirement between tumor and normal cells. Theoretically, nutritional support might enhance tumor growth but also susceptibility to chemotherapy. In either case, nutrition is a support modality that must be given with appropriate tumor-directed therapy if curative intent is the goal of treatment. Nutrition remains a consideration after therapy is completed. This generates different challenges. If further tumor-directed therapy is futile, the decision to continue nutritional support is difficult, but if the child is well, nutritional rehabilitation must be pursued. Finally, the cured child continues to benefit from dietary advice. Nutrition should be viewed for what it is: supplying the most basic need of children.

Bone mineral density (BMD) of the lumbar spine was measured in 97 long-term survivors of childhood cancer 5-23 years after diagnosis using dual-energy X-ray absorptiometry (DXA). They had been treated for acute leukemia (n = 22), brain tumors (n = 16), lymphomas (n = 16), Wilms' tumor (n = 10), neuroblastoma (n = 7) and other cancers (n = 26). The correlations between BMD and the Z-scores for weight for height, height for age and weight for age at diagnosis and follow-up were evaluated with stepwise multiple regression. Correlations with cumulative corticosteroid and radiation dose were examined with Spearman's correlation coefficient. The number of nature of fractures were noted. A BMD Z-score of below -2 was present in 13 and a BMD Z-score of -1 to -2 in 31 children. In total, a low BMD was observed in 45% of children. Height for age at follow-up correlated significantly with BMD Z-score. Increasing doses of cranial irradiation (18-54 Gy) were associated with lower BMD (p = 0.001, Spearman). This was true also for 22 children with acute lymphoblastic leukemia (ALL) who had received 18-24 Gy cranial irradiation (p = 0.04, Spearman). Fractures occurred in 14 children following trauma. The difference in BMD Z-scores of children with and without fractures did not achieve statistical significance although the majority of the children with fractures had low BMD Z-scores. The significant inverse correlation between height for age at follow-up and BMD must be interpreted with the realization that DXA is not a volumetric measurement of BMD and that short stature is associated with a smaller skeletal mass.

CD4, the cell-surface receptor for the human immunodeficiency virus (HIV), is a member of the immunoglobulin (Ig) gene superfamily. It contains 4 extracellular sequences homologous to Ig variable domains, the first of which (V1) is sufficient for binding to HIV. To develop CD4 as an anti-HIV therapeutic, we engineered a CD4 immunoadhesin (CD4-IgG)--a fusion protein containing the V1 and V2 domains of CD4 with the hinge and Fc regions of human Ig heavy chain. A chimeric protein of this type has several advantages compared to the soluble receptor, including a greatly extended in vivo half-life and greater avidity for HIV; moreover, like an antibody, it performs effector functions via its Fc domains, such as complement activation and antibody-dependent cell-mediated cytotoxicity. In vivo experiments show that CD4-IgG protects against HIV-I IIIB infection of chimpanzees when administered prior to viral challenge. In addition, CD4-IgG is transferred efficiently across the placenta from mother to fetus in rhesus monkeys. To evaluate its safety in humans, we conducted a phase-I clinical trial in adult patients with AIDS and AIDS-related complex. We found that, in a total of 16 patients, administration of CD4-IgG was well tolerated at doses up to 1000 micrograms/kg of body weight, with no important clinical or immunological toxicities noted. Given its unique properties, particularly the ability of CD4-IgG to cross the placenta, we plan to focus future clinical efforts on preventing infection of newborns via maternal-fetal transfer of HIV.

Early work on T-cell hybridomas lacking the T-cell-receptor (TCR) sub-unit CD3 eta had suggested a correlation between the presence of CD3 zeta-eta heterodimers and signalling leading to phosphatidyl-inositol (PI) turnover as well as activation-induced cell death. The cloning of CD3 eta has now allowed thorough and direct analysis of the signal transduction properties of CD3 zeta-zeta-, CD3 zeta-eta- and CD3 eta-eta-containing TCRs. We have found that all forms of the TCR are capable of transducing signals leading to PI turnover, Ca2+ mobilization, IL-2 production and cell-cycle arrest. CD3 zeta and CD3 eta utilize the same promoter which yields coordinate expression of both products, so that restricted CD3 eta expression in a sub-population of thymocytes is unlikely. Immunohistochemical methods employing an anti-CD3 eta-specific monoclonal antibody (MAb) show no detectable staining of thymic sections from adult mice, implying at best a low level of constitutive CD3 eta expression. In contrast, CD3 eta expression is readily detected in the majority of cortical thymocytes of CD3 eta transgenic mice using a Thy-1 promoter construct. However, over-expression of CD3 eta in mice transgenic for this polypeptide does not result in increased negative selection in vivo, consistent with the in vitro findings that induction of cell death is not strictly dependent on CD3 eta. Despite earlier reports of the detection of human CD3 eta protein, we find no CD3 eta message in human thymus or T cells. Cloning of the human CD zeta-eta genomic locus has demonstrated approximately 70% homology between the mouse and human genomic sequence, corresponding to the mouse CD3 eta-specific exon. However, translation of the DNA sequence does not result in a homologous amino acid sequence. Thus, there does not appear to be a CD3 eta protein in humans.