Heme-induced biomarkers associated with red meat promotion of colon cancer are not modulated by the intake of nitrite.

Red and processed meat consumption is associated with the risk of colorectal cancer. Three hypotheses are proposed to explain this association, via heme-induced oxidation of fat, heterocyclic amines, or N-nitroso compounds. Rats have often been used to study these hypotheses, but the lack of enterosalivary cycle of nitrate in rats casts doubt on the relevance of this animal model to predict nitroso- and heme-associated human colon carcinogenesis. The present study was thus designed to clarify whether a nitrite intake that mimics the enterosalivary cycle can modulate heme-induced nitrosation and fat peroxidation. This study shows that, in contrast with the starting hypothesis, drinking water added with nitrite to mimic the salivary nitrite content did not change the effect of hemoglobin on biochemical markers linked to colon carcinogenesis, notably lipid peroxidation and cytotoxic activity in the colon of rat. However, ingested sodium nitrite increased fecal nitroso-compounds level, but their fecal concentration and their nature (iron-nitrosyl) would probably not be associated with an increased risk of cancer. We thus suggest that the rat model could be relevant for study the effect of red meat on colon carcinogenesis, in spite of the lack of nitrite in the saliva of rats.

Alcohol consumption and digestive cancer mortality in Koreans: the Kangwha Cohort Study.

BACKGROUND: Alcohol consumption is a known risk factor for cancers of the mouth, esophagus, liver, colon, and breast. In this study, we examined the association between alcohol consumption and digestive cancer mortality in Korean men and women. METHODS: A cohort of 6291 residents of Kangwha County who were aged 55 years or older in March 1985 were followed to 31 December 2005-a period of 20.8 years. We calculated the relative risks of cancer mortality with respect to the amount of alcohol consumed. Cox proportional hazard model was used to adjust for age at entry, smoking, ginseng intake, education status, and pesticide use. RESULTS: In men, the risks of mortality from esophageal cancer (relative risk [RR], 5.62; 95% confidence interval [CI], 1.45-21.77) and colon cancer (RR, 4.59; 95% CI, 1.10-19.2) were higher among heavy drinkers, as compared with abstainers. The risks of mortality from colon cancer and bile duct cancer rose with increasing alcohol consumption; these trends were positive and statistically significant (P = 0.04 and P = 0.02, respectively). When participants were stratified by type of alcoholic beverage, soju drinkers had higher risks of mortality from esophageal cancer and colon cancer than makkoli drinkers. In women, the risk of digestive cancer mortality was higher among alcohol drinkers than abstainers, but this difference was not statistically significant. CONCLUSIONS: Alcohol consumption increases mortality from esophageal cancer and colon cancer in men.

Extensive oral shedding of human herpesvirus 8 in a renal allograft recipient.

INTRODUCTION: Studies were conducted to investigate changes in the extent of human herpesvirus 8 (HHV-8) shedding and diversity of HHV-8 strains in the mouth of a renal allograft recipient who developed cutaneous post-transplantation Kaposi's sarcoma. METHODS: Matched oral and blood samples were obtained from a Saudi Arabian renal allograft recipient from 3 days before to 38 weeks after transplantation, and from his kidney donor. Polymerase chain reaction (PCR) protocols to amplify selected HHV-8 sub-genomic regions were applied to detect and quantify HHV-8 DNA. Sequence diversity was determined by cloning the PCR products and subjecting them to denaturing gradient gel electrophoresis and to nucleotide sequencing. RESULTS: Before transplantation, the recipient was seropositive for anti-HHV-8 immunoglobulin G, but the donor was seronegative; HHV-8 DNA could be detected in the recipient's blood, whole-mouth saliva (WMS) and buccal exfoliates, and the salivary viral load was estimated as 2.6 million genome-copies/ml. Post-transplantation, the recipient's salivary viral load initially increased to 4.1 million genome-copies/ml, and thereafter declined precipitously, coinciding with an increase in the dosage of valaciclovir given; HHV-8 DNA was detected most often in WMS compared with parotid saliva, and buccal and palatal exfoliates. Carriage of multiple HHV-8 strains was evident in blood and oral samples; whereas before transplantation strains belonging to genotypes A1 and A5 were observed, after transplantation genotype A5 strains became dominant and A2 strains emerged. CONCLUSION: Immunosuppression and antiviral prophylaxis may interact to influence the spectrum of oral HHV-8 strains and the extent of post-transplantation HHV-8 shedding into the mouth.

Intrathoracic cancer of the splenic flexure.

Blunt traumatic rupture of the diaphragm is a well known but uncommon event of thoracoabdominal traumatic injuries. It occurs in 1-5% of polytrauma patients and requires a high degree of suspicion for a rapid diagnosis. The frequency of delayed diagnosis is difficult to be estimated and up to 30% of blunt diaphragmatic ruptures present late. A case of herniated splenic colic flexure through a defect in the left hemidiaphragm and the subsequent development of colon cancer in this area are presented. We emphasize the importance of making a prompt diagnosis in order to avoid further morbidity and mortality in this rare clinical entity.

Newly Designed Silica-Containing Redox Nanoparticles for Oral Delivery of Novel TOP2 Catalytic Inhibitor for Treating Colon Cancer.

Although oral drug delivery is the most common route of drug administration, the conventional polymeric nanocarriers exhibit a low drug loading capacity and low stability in the gastrointestinal (GI) environments. In this study, a newly designed silica-containing redox nanoparticle (siRNP) with reactive oxygen species (ROS) scavenging capacity is developed as an ideal oral nanocarrier for a novel hydrophobic anticancer compound BNS-22 to treat colitis-associated colon cancer in vivo. Crosslinking of silica moieties significantly enhances the stability under acidic conditions and improves BNS-22 loading capacity of siRNP compared to the conventional redox nanoparticle. After oral administration to mice, BNS-22-loaded siRNP (BNS-22@siRNP) remarkably improves bioavailability and colonic tumor distribution of BNS-22. As the result, BNS-22@siRNP significantly inhibits the tumor progression in colitis-associated colon cancer mice compared to other control treatments. It is noteworthy that no systemic absorption of siRNP carrier is observed after oral administration. Interestingly, orally administered BNS-22@siRNP significantly suppresses the adverse effects of BNS-22 owing to its ROS scavenging capacity, and no other noticeable toxicities are observed in mice treated with BNS-22@siRNP although siRNP is localized in the GI tract. Our results indicate that siRNP is a promising oral drug nanocarrier for cancer therapy.

Carcinogen binding to various types of dietary fiber.

The percent of the carcinogen 1,2-dimethylhydrazine (DMH) bound to a variety of fibers, such as wheat bran, corn bran, citrus pulp, citrus pectin, and alfalfa, was examined at pH values ranging from 1 to 12. The percent of DMH bound to wheat bran increased from 4% at PH 1 to 55% at pH 2 to 77% at pH 12. A sharp rise in carcinogen binding to corn bran occurred between pH 5% of the DMH was bound and pH 8 where 51% of the DMH was bound. The percent of DMH bound to dehydrated citrus pulp also increased as the pH increased with 10% binding observed at pH 1 and with 57% binding observed at pH 12. Between pH 2 and pH 7, the percent of DMH bound to pectin decreased from 60 to 11%. As the pH became more basic, the percent of DMH bound to pectin increased to 42% at pH 12. The sharpest rise in the percent of DMH bound to alfalfa meal occurred between pH 10.5 and pH 12.0. Results from this experiment showed that the affinity to various types of dietary fibers for the colon carcinogen DMH was differentially affected by pH. These results suggested that the protective effect of certain types of dietary fiber against chemically induced colon cancer my in part be attributed to enhanced carcinogen binding by dietary fiber in the colon.

Effect of dietary undegraded carrageenan on colon carcinogenesis in F344 rats treated with azoxymethane or methylnitrosourea.

The effect of dietary undegraded carrageenan (Viscarin 402) on colon carcinogenesis was studied in female inbred F344 rats. Weanling rats were fed semipurified diets containing 0 or 15% undegraded carrageenan. At 7 weeks of age, all animals except controls were given azoxymethane (AOM) s.c. at a dose rate of 8 mg/kg body weight per week for 10 weeks or methylnitrosourea (MNU) intrarectally at a dose level of 2 mg/rat twice a week for 3 weeks. The AOM groups were autopsied 40 weeks and the MNU groups 30 weeks after the first injection. No tumors were induced in the colon or in other organs of untreated rats fed the control diet. One untreated rat fed the carrageenan diet showed a colon adenoma. The animals fed the carrageenan diet and treated with AOM or MNU had a higher incidence of colorectal tumors (number of rats with colorectal tumors and number of tumors per tumor-bearing rat) than did those fed the control diet and treated similarly. The undegraded carrageenan (Viscarin 402) in the diet had an enhancing effect in colorectal carcinogenesis in rats evoked by AOM or MNU.

Diet and excretion of bile acids.

In recent years, salient advances have taken place in the knowledge of the interaction of diets containing high-fat and certain type of fibers and the production of bile acids potentially relevant in the etiology of colon cancer. Other studies also indicate that a high intake of certain dietary fibers, in spite of high dietary fat, not only leads to an increase in stool bulk, thus diluting carcinogens and promoters in the gut, but also modifies the metabolism of these putative substances. These studies thus suggest that both high intake of total fat and low intake of certain fibers may be necessary for the full expression of risk to colon cancer.

A double-blind study on the effect of purified cellulose dietary fiber on 1,2-dimethylhydrazine-induced rat colonic neoplasia.

The incidence, distribution, size, and histopathology of grossly visible colonic tumors induced by parenteral administration of 1,2-dimethylhydrazine were examined in rats fed either a chemically defined fiber-free diet or a nutritionally and calorically equivalent diet containing a purified fiber component, microcrystalline cellulose. This double-blind study indicates that cellulose ingestion was associated with reduced numbers of animals involved with colonic neoplasia as well as a reduction in the total numbers of colonic tumors. Furthermore, this protective effect of cellulose appears to be time dependent and associated with a shift in tumor distribution from the proximal colon to a more distal site. Cellulose fiber had no apparent effect on colonic tumor size, histopathology, or the incidence of other tumors known to occur in this experimental animal model. This study strongly supports the hypothesis that fiber is an important protective agent against colonic neoplasia development. While the mechanism for this protective effect remains obscure, it appears to be temporally related to the duration of fiber ingestion as well as to a differential fiber effect on either the luminal content or the mucosa of the proximal and distal colon.

Interaction of dietary fiber with other dietary components: a possible factor in certain cancer etiologies.

Dietary fiber is a highly interacting dietary component and is made up of a wide variety of enzyme-indigestible polymers: cellulose, pectins, gums, mucilages, lignin, and water-insoluble hemicelluloses. The study of the effect of dietary fiber on prevention of cancer, specifically of colonic cancer, cannot be carried on without considering that: 1) various types of dietary fiber have different metabolic effect; 2) other components of the diet (e.g., amount of fat) may influence the way dietary fiber affects the colonic environment; 3) the overall effect of dietary fiber may be the sum of effects on fecal bulk, colonic microflora pattern and metabolites, dilution of carcinogens, colonic pH, transit time, alteration of nutrient absorption, and postprandial hormonal function. It is unlikely that dietary fiber can be studied in isolation in experimental diets unless great care is taken to consider all interactions with other dietary components.

Colonic-rectal cancer: fiber and other dietary factors.

The prevalence of colonic-rectal cancer is generally directly related to the fat content and inversely related to the fiber content of diet. In the few exceptions to this generalization, tumor prevalence is more closely related to fiber than to fat. Hypotheses have been postulated to explain the possible ways in which dietary fiber may protect against colonic-rectal cancer and to account for the close relationships between the geographical distribution of these tumors and that of certain other diseases.

Colon cancer and diet, with special reference to intakes of fat and fiber.

Colon cancer, rare in the past, and in developing populations, currently accounts for 2 to 4% of all deaths in Western populations. Evidence suggests the primary cause to be changes in diet, which affect the bowel milieu intérieur. It is possible that in sophisticated populations, the higher concentrations of fecal bile acids and sterols, and longer transit time, favor the production of potentially carcinogenic metabolites. Of secular changes in diet, evidence suggests that the following may have etiological importance: 1) the fall in intake of fiber-containing foods with its effects on bowel physiology, and 2) the decreased fiber but increased fat intakes, in their respective capacities to raise concentrations of fecal bile acids, sterols, and other noxious substances. For possible prophylaxis against colon cancer, recommendations for a lower fat intake, or a higher intake of fiber-containing foods (apart from fiber ingestion from bran) are extremely unlikely to be adopted. For future research, western populations with considerably lower than average mortality rates, e.g., Seventh Day Adventists, Mormons, the rural Finnish population, as well as developing populations, demand intensive study. Also requiring elucidation are the respective roles of diet and of genetic constitution on concentrations of fecal bile acids, etc., and on transit time, in prone and nonprone populations.

Wheat bran as an etiologic factor in certain diseases. Some second thoughts.

The author questions "the bran hypothesis" that a deficiency of natural fiber--wheat bran in particular--is responsible for a number of prevalent diseases in Western societies, namely diverticular disease, cancer of the colon, gallstones, and myocardial disease. In re-examining the hypothesis, he cites reports which fail to support the theory. For instance, the incidence of diverticular disease in women has increased since 1925, yet there is no evidence that their diets have changed or are different from those of men. Also, it is a mistake to equate wheat bran with fiber in general, and it cannot be shown that dietary fiber in general has declined. In addition, clinical studies have failed to show beneficial results in treating diverticular disease and irritable colon by adding bran to the diet. Similar problems arise in testing the hypothesis that natural fiber can prevent cancer of the colon and lower serum cholesterol and triglycerides. Recent interest in dietary fiber is welcome, for it has been grossly neglected, but much research is still needed to place it in proper perspective.

Proliferon: the functional unit of rapidly proliferating organs.

Continuously replicating organs are generally composed of several cell population types. These may be divided according to their function into two classes: 1. parenchyma: cells destined to perform a certain metabolic function peculiar to the organ under study, 2. supporting cell populations, consisting of fibroblasts and vascular supply always accompanied by nerve fibers. The kinetics of all the cells are highly coordinated. They all share one progenitor region. It is postulated that in this common progenitor region the two cell population classes are assembled into complex units denominated as proliferons. The proliferon starts its existence as a whole, matures as a whole and disintegrates at the organ periphery. It consists of four basic elements: parenchyma, connective tissue, blood vessels and nerve fibers. This model has been previously called upon to describe the kinetics of the rodent incisor tooth and the intestinal mucosa. It is assumed to be the elementary functional unit of all rapidly proliferating organs such as: skin, hair, endometrium, bone marrow, intestinal mucosa and rodent incisor.

Western diet and Western diseases: some hormonal and biochemical mechanisms and associations.

Breast cancer, prostate cancer, coronary heart disease and colon cancer belong to the so-called Western diseases and a general opinion is that diet is a significant or even the main factor increasing incidence and mortality of these diseases in the Western world. This review describes studies carried out in this department for about 10 years, many in collaboration with scientists abroad, and with the aim to clarify some of the connections between the diet and sex hormone, lipid and bile acid metabolism. A Western-type diet elevates plasma levels of sex hormones and decreases the sex hormone binding globulin concentration, increasing the bioavailability of these steroids. The same diet results in low formation of mammalian lignans and isoflavonic phytoestrogens. These diphenolic compounds seem to affect hormone metabolism and production and cancer cell growth by many different mechanisms making them candidates for a role as cancer protective substances. The precursors of these diphenols are to be found in fiber-rich unrefined grain products, various seeds, beans and probably also in pulses, peas and berries. Some types of fiber seem to influence sex hormone and bile acid metabolism mainly by partial interruption of the enterohepatic circulation, by alteration of intestinal metabolism and by increasing fecal excretion of these compounds. The sex hormone pattern found in connection with a Western-type diet is prevailing in the breast cancer patients, but is only partly a result of the diet.