Nutritional factors in cancer prevention

Current epidemiologic and laboratory evidence suggests that nutritional factors may play an important role in chemoprevention, although the relative importance of that role for the various micronutrients and dietary constituents is still unclear. The complexity of this area of investigation and practice clearly requires knowledge of the relevant measurement tools, chemistry, biology, and food science, and also the limitations that must be considered in the interpretation of nutritional data. Despite the challenges encountered in translation to clinical research and practice, nutrition remains a promising area of chemoprevention, likely to yield important information and strategies with a large public health impact.     

Dietary factors and prevention of colon cancer

We are interested in the influence of trabeculectomy (TE) with releasable sutures to corneal curvature in the early postoperative period. 35 eyes of 31 patients were followed after operation. Corneal topography was made on the Topograph Opticon 2000 one day before, 1st day, 1st week, 1st month and during 6-12 months after operation. Astigmatism after operations was the highest on 1st day +3.7 D, which means elevation of about +2.8 D. During 1st month postoperative astigmatism was decreased by about 2.0 D, it is about +0.8 D more than before operation. During 6-12 months after operation temporary astigmatism nearly disappears, it only makes +0.25 D. The axis of astigmatism was without larger alterations. Small temporary changes were seen according to the place of TE. Temporary astigmatism was observed immediately after the extraction of the releasable sutures. Astigmatism after operation was influenced by the rate of filtration during the short postoperative time and also after extraction of the releasable suture.     

Nutritional factors and hypertension

Hypertension is a major risk factor for coronary artery disease, stroke, renal failure, and peripheral vascular disease. The importance of preventing hypertension and controlling blood pressure in patients with hypertension is well established and is associated with reduced cardiovascular morbidity and mortality rates. Treatment guidelines should consider the merits of dietary changes in addition to pharmacologic therapy in the control of mild hypertension.     

Prognostic factors of colon cancer from a molecular biology standpoint

It has been reported that several genes may be good indicators for determining biological behavior, including the prognosis, of colorectal cancers. We have summarized these reported genes, such as tumor suppressor gene, oncogenes, metastasis suppressor gene, adhesion molecules, growth factors, proteinases, and others, including microsatellite instability. Some of the genes such as p53, DCC, c-met, or matrix metalloproteinase are considered to be reliable for determining biological aggressiveness. We introduced several interesting genes which we are focusing using cDNA subtraction library analysis. We hope that these genes are well combined for best analysis of the biological behavior of colorectal cancers and use for practical clinical analysis. In addition, we hope that novel important genes indicative for prognosis will be found.     

Dietary risk factors for colon cancer in a low-risk population

Spontaneous EEG was registered under different activity conditions in 26 volunteers. The EEG synchronisation parameters were compared with the geomagnetic and solar activity on the day of experiment. A positive correlation of the EEG data with the geomagnetic activity was revealed, being most obvious in the frontal and central areas. A negative correlation between some local EEG synchronisation parameters and different indices of the solar activity, was also revealed. The degree of synchronisation of the spontaneous EEG seems to reflect sensitivity of the human nervous system to the Earth's magnetic field. A stressor response to strong short-term disturbances in the geomagnetic field reveals itself in the form of enhancement of the EEG global synchronisation. A sedative effect of slow magnetic oscillations is locally revealed in the parameters of the EEG synchronisation within the left hemisphere as well as the interhemisphere synchronisation.     

The nonfermentable dietary fiber lignin alters putative colon cancer risk factors but does not protect against DMH-induced colon cancer in rats

The effect of supplementation of the diet with autohydrolyzed lignin on 1,2-dimethylhydrazine (DMH)-induced colon carcinogenesis was studied using 112 male Sprague-Dawley rats. Rats received eight weekly injections of DMH (9.5 mg/kg s.c.) or the saline vehicle solution and then were maintained on a basal AIN-76 fiber-free diet or the basal fiber-free diet plus 5% or 10% (wt/wt) lignin for 24 weeks. Rats were killed 32 weeks after the start of the experiment. Colon tumor incidence, location, and multiplicity were determined. Body weight, caloric intake, fecal dry weight, gut transit time, pH of cecal contents, and total fecal bile acid excretion were measured. Supplementation of the diet with 5% or 10% lignin resulted in increased fecal dry weight and total fecal bile acid excretion and in decreased gut transit time, colon pH, and fecal bile acid concentration. Dietary lignin did not significantly affect colon tumor incidence or multiplicity compared with the fiber-free diet. Thus dietary supplementation with autohydrolyzed lignin, a food fiber with good bulking characteristics, had a significant effect on several factors that have previously been linked to reduction of colon cancer risk, but the consumption of high levels of lignin did not decrease the risk for colon cancer.     

Nutritional and socioeconomic factors in relation to prostate cancer mortality: a cross-national study

BACKGROUND: Large international variations in rates of prostate cancer incidence and mortality suggest that environmental factors have a strong influence on the development of this disease. The purpose of this study was to identify predictive variables for prostate cancer mortality in data from 59 countries. METHODS: Data on prostate cancer mortality, food consumption, tobacco use, socioeconomic factors, reproductive factors, and health indicators were obtained from United Nations sources. Linear regression models were fit to these data. The influence of each variable fit in the regression models was assessed by multiplying the regression coefficient b by the 75th (X75) and 25th (X25) percentile values of the variable. The difference, bX75 - bX25, is the estimated effect of the variable across its interquartile range on mortality rates measured as deaths per 100000 males aged 45-74 years. Reported P values are two-sided. RESULTS: Prostate cancer mortality was inversely associated with estimated consumption of cereals (bX75 - bX25 = -7.31 deaths; P = .001), nuts and oilseeds (bX75 - bX25 = -1.72 deaths; P = .003), and fish (bX75 - bX25 = -1.47 deaths; P = .001). In the 42 countries for which we had appropriate data, soy products were found to be significantly protective (P = .0001), with an effect size per kilocalorie at least four times as large as that of any other dietary factor. Besides variables related to diet, we observed an association between prostate cancer mortality rates and a composite of other health-related, sanitation, and economic variables (P = .003). CONCLUSIONS: The specific food-related results from this study are consistent with previous information and support the current dietary guidelines and hypothesis that grains, cereals, and nuts are protective against prostate cancer. The findings also provide a rationale for future study of soy products in prostate cancer prevention trials.     

Are dietary factors involved in DNA methylation associated with colon cancer?

Albuterol is a quickly acting beta-2 adrenergic agonist bronchodilator widely used by asthmatics. Because recent case-control studies have suggested a relationship between the increase in mortality of asthmatics over the past decade and the use of beta 2-adrenergic agonists in the control of asthma, concern has developed regarding the potential cardiotoxicity of beta 2-specific adrenergic agonists, including albuterol. The aim of this investigation was to assess the potential for cardiotoxicity of inhaled albuterol dry powder in rats, monkeys, and dogs. All species were exposed to an aerosol of albuterol 1 h per day, 7 days per week, for at least 2 weeks. Control groups were exposed to filtered conditioned air and handled in the same manner as the albuterol-exposed animals. Plasma concentrations of albuterol confirmed systemic exposure. The daily inhaled dose received by the animals was calculated based on measured respiratory minute volumes, published respiratory tract deposition data, as well as HPLC-determined particle size distribution data and aerosolized albuterol concentrations. Multiples of the maximum daily clinical dose (presentation of 15 micrograms/kg in a 70-kg human) were approximately 0.25- to 2500-fold in the rat, 9- to 100-fold in the monkey, and 0.5- to 90-fold in the dog. No findings attributed to albuterol were observed in the monkey. Tachycardia and transient hypokalemia occurred in rats at multiples of 1.5 times or greater of the maximum clinical dose. Absolute and relative heart weights increased in rats receiving multiples of 47 times or greater of the maximum human dose. In the absence of histopathologic findings, the increases in rat heart weights were considered a physiologic hypertrophic response to tachycardia. In dogs tachycardia and transient hypokalemia occurred at all doses tested. Slight to mild fibrosis in the papillary muscles of the left ventricle of the heart occurred in dogs at multiples > or = 19 times the clinical dose. The cardiovascular effects observed were consistent with the known pharmacologic action of beta 2-adrenergic agonists. Due to the lack of toxicologically relevant findings in rats and monkeys and the wide safety margin in dogs, the findings in this study do not suggest a cardiotoxicity risk in the human population after repeated exposures to clinical doses of albuterol currently used in the treatment of asthma.     

Nutritional factors and colon carcinoma: a case-control study involving French Canadians in Montréal, Quebec, Canada

BACKGROUND: In a population-based case-control study of colon carcinoma and nutrition involving the francophone community in Greater Montreal, a total of 402 cases (200 males and 202 females) and 668 controls (239 males and 429 females) were interviewed. METHODS: Cases from 1989-1993 were identified through the admission offices of 5 major francophone teaching hospitals in Montreal and were ages 35-79 years. Controls matched by age, place of residence, and language were selected by a modified random digit dialing method. Information on dietary intake was collected with a quantitative food frequency questionnaire. RESULTS: No associations were evident between colon carcinoma and total energy, protein, or carbohydrate consumption, whereas a suggestive inverse association was found with total fat intake, with an odds ratio (OR) of 0.78 (P = 0.0637), and with saturated fat intake as well (OR = 0.71, P = 0.0893). A strongly significant inverse association was found with dietary fiber (OR = 0.50, P = 0.0018). The strongest inverse association concerning fiber was found with fiber from vegetable sources (OR = 0.57, P = 0.0096), and a suggestive (although nonsignificant) inverse association (OR = 0.74, P = 0.0687) was found with fiber from fruits. Calcium was inversely associated with risk (OR = 0.69, P = 0.0411), as was dietary intake of vitamin A (OR = 0.67, P = 0.0162), retinol, (OR = 0.069, P = 0.0409), vitamin E (OR = 0.53, P = 0.0028), and alphatocopherol (OR = 0.63, P = 0.0256). Although there was no association demonstrated between dietary beta-carotene intake and risk, a suggestive (although nonsignificant) inverse association with intake of other types of carotene was observed (OR = 0.76, P = 0.0740). No association was found between intake of other nutrients investigated in this study and risk of colon carcinoma. CONCLUSIONS: There is strong evidence from epidemiologic studies that high intake of fat and meat are risk factors for colorectal carcinoma in humans, whereas high intake of vegetable and fruit are inversely associated with risk of colon carcinoma. The findings from this study are in agreement with this observation.     

Physical activity and colon cancer

Heart disease and cancer, the major causes of mortality and morbidity in Western countries, have common risk factors. Exercise appears to reduce the risk of cardiovascular disease, but its role with respect to primary prevention of cancer has not been emphasized. Here we evaluate the epidemiological studies dealing with exercise and colon cancer. Despite the fact that different methods of assessing the amount of typical exercise of individuals and the different types of physical activity measured (occupational and recreational), there is remarkably consistent evidence that people who are highly physically active could be at a reduced risk of cancer of the colon. An analysis of case-control and cohort studies suggests that exercise might reduce the risk, at least in men, by up to one-third. We conclude that exercise has been overlooked as a potentially useful, effective, and acceptable method for reducing the risk of colon cancer.     

青年结直肠癌分析

目的:探讨青年结直肠癌的临床特征.方法:收集48例35岁以下的结直肠癌病例临床资料并进行系统性分析.结果:青年人结直肠癌主要临床表现为粘液血便或便血、腹痛、大便习惯改变,肿瘤主要在直肠及乙状结肠,组织学类型以分化不良为主,Duke's分期以C、D期为主,根治率43.75%,5年生存率为28.21%.结论:青年结直肠癌临床症状不典型,恶性程度高,手术根治率低,预后差.早期诊断,早期治疗是提高生存率的关键.     

Cell adhesion molecules and colon cancer

There is a general consensus that cell-cell and cell-matrix interactions determine, at least in part, the behaviour of colon cancer. The biological mediators responsible for these interactions are cell adhesion molecules belonging to several major receptor families called integrins, cadherins, the immunoglobulin superfamily, hyaluronate receptors and mucins. Emerging data indicate that certain patterns of adhesion receptor expression are associated with more aggressive disease. The present review examines the role of each of the receptor families in the development and progression of large bowel cancer.     

Nutritional factors and Helicobacter pylori infection in Colombian children

The reliability (internal consistency and alternate form) of the trait version of the Positive and Negative Mood Scales in referred samples was found to be high, and the concurrent and discriminate validity was found to be moderate. As expected, means of the Positive Mood Scales were significantly higher in nonreferred samples and means of the Negative Mood Scales were significantly higher in referred samples. The alternate forms for each scale were equivalent. The Positive and Negative Mood Scales seem to be ready for use in research.     

Hepatocyte extracellular matrix modulates expression of growth factors and growth factor receptors in human colon cancer cells

A new algorithm for analysis of the homology and genetic semihomology in protein sequence is described. It assumes the close relation between the compared amino acids and their codons in related proteins. The algorithm is based on the network of the genetic relationship between amino acids and, thus differs from the commonly used statistical matrices. The results obtained by using this method are more comprehensive than used at present, and reflect the actual mechanism of protein differentiation and evolution. They concern: (1) location of homologous and semihomologous sites in compared proteins; (2) precise estimation of insertion/deletion gaps in non-homologous fragments; (3) analysis of internal homology and semihomology; (4) precise location of domains in multidomain proteins; (5) estimation of genetic code of non-homologous fragments; (6) construction of genetic probes; (7) studies on differentiation processes among related proteins; (8) estimation of the degree of relationship among related proteins; (9) studies on the evolution mechanism within homologous protein families and (10) confirmation of actual relationship of sequences showing low degree of homology.     

Gene therapy for colon cancer

The enormous number of newly diagnosed cases of colorectal cancer that occur each year and the lack of agents that are highly effective for all patients underscore the need for novel approaches to combating the disease. Gene therapy as a developing treatment modality is already well established, with a number of trials ongoing and a vast range of other approaches being assessed in animal and cell culture experiments. In this brief review, we have discussed five gene therapy trials in colon carcinoma that are ongoing or in the approval process in the United States. The gene therapy approaches being employed can be divided into three major categories: (1) enzyme/prodrug systems (HSVtk/ganciclovir; CD/5-fluorocytosine); (2) tumor suppressor gene replacement therapy with wild-type p53; and (3) immune-gene therapy which is based on cytokine or tumor antigen expression to induce tumor immunity (e.g., CEA). Replication-deficient recombinant adenoviral vectors are predominantly used for colon cancer gene therapy, because they can be produced at high titer and they readily infect a number of different cell types. One trial uses polynucleotide therapy for antitumor immunization with intramuscular injection. All of these studies are phase I trials, principally designed to evaluate safety, but they will also provide data on gene delivery. Some trials may provide some insight into potential therapeutic effects. We have alluded to some of the concerns on toxicity related to the use of adenovirus, risks and side effects from transgenes, lack of tumor-specificity of transgene expression, and potential problems with efficient gene delivery to solid tumors. The clinical trials, however, will provide insight that will inform design of future studies with respect to dose, form, and frequency of administration, as well as to the value of biologic and clinical endpoints. The molecular analysis of the fundamental basis of colon cancer has moved at a remarkable pace and that progress seems set to continue. Thus, the basic foundations for gene therapy are undoubtedly in place: a clinical need; growing understanding of basic tumor biology; and ever-improving delivery systems. The field is at a very early stage in its evolution, and one concern is that the considerable hurdles that must be overcome are seen as examples of the failure of cancer gene therapy; however, we believe these challenges will be overcome. The authors also believe that colon cancer gene therapy is likely to take new directions, such as use as adjuvant to radical surgery, rather than attempts to treat end-stage disease when the liver is replaced by metastases. Other new directions might include prophylactic gene-based immunization against a panel of well-characterized tumor antigens, at least for persons shown to be at high risk of colon cancer because of genetic or other predisposition. A marriage between gene therapy approaches and conventional anticancer treatments such as radiotherapy and chemotherapy also seems likely. There is already evidence of this move with demonstration of synergism between p53 replacement and radiotherapy and chemotherapy. It is also likely that therapies will be developed that combine elements from the cancer gene therapies discussed previously, namely, suicide gene transfer, immune modulation, and modulation of defective cancer genes. Perhaps one of the main concerns is not that researchers in cancer gene therapy want to walk before they can run, but that the public and government agencies believe they can. The next 10 years will be an interesting time in the development of novel treatments against colon cancer.