Suppression of intestinal polyp development by low-fat and high-fiber diet in Apc(delta716) knockout mice.

Most epidemiological and animal studies show a positive correlation of the dietary intake of fat with the incidence of colon cancer, whereas an inverse correlation of the dietary intake of fiber. In rats fed a diet low in fat and high in wheat bran fiber and calcium, a significant decrease was reported in the number of azoxymethane-induced aberrant crypt foci compared with those fed a high-fat, low-fiber and low-calcium diet. Mutations in the human APC gene play a key role, not only in familial adenomatous polyposis, but also in many sporadic cancers of the entire digestive tract.

Inhibition by wheat bran cereals of the development of aberrant crypt foci and colon tumours.

As variation in both type of fibre and its physical properties can influence physiological effects, the effects of different dietary levels (1, 4, 8%, w/w) of unprocessed wheat bran (WB) were compared with those of two of its processed commercial formulations used in breakfast cereals, on the formation of aberrant crypt foci (ACF) and colon tumours in Fischer 344 rats following azoxymethane (AOM) administration. All diets were high in fat (20 g/100 g) and low in calcium (0.2%, w/w).

Absence of p53 gene mutations in rat colon carcinomas induced through the synergistic interaction between methylazoxymethanol and X-irradiation.

p53 is one the most frequently mutated genes found in human colonic tumors. Because colonic neoplasms induced in rats by certain chemical carcinogens are similar to human colonic tumors in their histological features and proliferation characteristics, the rat has been used as an experimental model to study the pathogenesis of colon cancer. However, p53 mutations were not detected in the chemically induced colonic tumors analyzed for p53 mutations.

Microsatellite instability in aberrant crypt foci from human colons.

Aberrant crypt foci (ACF) are distinct microscopic lesions of the colon thought to be the earliest identifiable precursors of colon cancer. As precursors of colon cancer, ACF may contain mutations in genes that are altered early in colorectal tumorigenesis. Candidates for these genes include APC, K-Ras, and those of the DNA mismatch repair system.

A rapid dual organ rat carcinogenesis bioassay for evaluating the chemoprevention of breast and colon cancer.

In this study we evaluated the effect of dietary administration of a high fat, low fiber diet (HRD) with or without 2% phytic acid (PA) on the development of mammary cancer and/or colon cancer in rats exposed to methylnitrosourea (MNU), azoxymethane (AOM) or MNU + AOM. The rats were fed a HRD alone or a HRD + 2% PA. At the end of week 2, the rats were given either a s.

Dietary fiber and the chemopreventive modelation of colon carcinogenesis.

Comparative international epidemiological data indicate that the difference between the highest and lowest colon cancer incidence is approximately 10-fold. This suggests that the dominant causes of colon cancer are environmental rather than genetic in origin, with the dominant environmental cause being the typical diet of Western industrialized countries. Many epidemiological and experimental studies have suggested an important role for dietary fiber in the prevention of colon cancer.

The effect of dietary fat on the promotion of mammary and colon cancer in a dual-organ rat carcinogenesis model.

Female Sprague-Dawley rats (n = 270) were randomly divided into nine subgroups (30 rats/group) and fed diets with fat contents ranging from 5% to 45% of total energy, in which fat was isocalorically substituted for carbohydrates. At Week 3, the rats were given a single injection of methylnitrosourea (MNU, 50 mg/kg body wt). At Weeks 4 and 5, rats were given an injection of azoxymethane (AOM, 15 mg/kg body wt sc).

Absence of p53 gene mutations in rat colon carcinomas induced by azoxymethane.

The K-ras and p53 genes are two of the most frequently mutated genes found in the human colonic tumors. Since azoxymethane (AOM) induced rat colonic neoplasms are similar to human colonic tumors in their histological features and proliferation characteristics, the rat has been used as an experimental model to study the pathogenesis of colon cancer in humans. Although the presence of K-ras point mutations has been reported in AOM induced rat colonic tumors, there are no reports describing the frequency for mutation of the p53 gene in these tumors.

Inhibition of progression of aberrant crypt foci and colon tumor development by vitamin E and beta-carotene in rats on a high-risk diet.

In this study we evaluated the effect of dietary administration of a high-fat, low-fiber diet (HRD) supplemented with Vitamin E, beta-carotene or folic acid and wheat bran on the growth of pre-existing aberrant crypt foci (ACF) that had been induced in Fischer-344 rats exposed to azoxymethane (AOM) and a HRD for 10 weeks. The rats (25 rats/dietary group) were fed a HRD for 2 weeks and were then given 2 subcutaneous injections of AOM (15 mg/kg body weight) while the rats continued on the HRD. After 6 weeks, rats were either maintained on the HRD (control) or crossed over to a HRD containing non-toxic levels of either Vitamin E, beta-carotene, folic acid or wheat bran.

Effect of beta-carotene and wheat bran fiber on colonic aberrant crypt and tumor formation in rats exposed to azoxymethane and high dietary fat.

The typical high-fat, low-fiber American diet promotes colon cancer. An alternative to radical changes in dietary habits is to reinforce the diet with cancer protectors. Experiments to evaluate the effects of beta-carotene in the presence of high fat and low and high dietary levels of wheat bran fiber were designed using the Fischer-344 rat colon cancer model.

Sequential analysis of K-ras mutations in aberrant crypt foci and colonic tumors induced by azoxymethane in Fischer-344 rats on high-risk diet.

Forty Fischer-344 male rats were given a high-risk diet (HRD) that was high in fat, low in fiber and low in calcium. After 4 weeks, the rats were given two weekly s.c.

Potential synergism between wheat bran and psyllium: enhanced inhibition of colon cancer.

In this study we compared the influence of high fat (20% w/w) diets that combine low levels of calcium (0.18% w/w) and low (1% w/w), medium (4% w/w) and high (8% w/w) levels of dietary fiber from wheat bran (WB), with high (8% w/w) levels of dietary fiber from psyllium (PS) alone or in various combinations with WB, on the induction of colon tumors in Fischer-344 rats following exposure to azoxymethane (AOM). The rats were fed the experimental diets for 2 weeks, and then were given two s.

Fecal bile acid excretion and composition in response to changes in dietary wheat bran, fat and calcium in the rat.

The effect and possible interactive influence of different dietary amounts of wheat bran, fat and calcium on the fecal excretion, concentration and composition of bile acids was studied in Fischer-344 rats. The fecal bile acids were analyzed using gas-liquid chromatography. Dietary wheat bran increased both total bile acid excretion and fecal weight without changes in fecal bile acid concentration.

The effect of high-risk and low-risk diets on aberrant crypt and colonic tumor formation in Fischer-344 rats.

Eighty Fischer-344 male rats were divided into eight groups. Half the groups were given a high-risk diet (HRD) that was high in fat, low in fiber and low in calcium, while the remaining groups were given a low-risk diet (LRD) that was low in fat, high in fiber and high in calcium. After 4 weeks, four groups were then given two weekly s.

Magnesium and calcium absorption in Fischer-344 rats influenced by changes in dietary fibre (wheat bran), fat and calcium.

Magnesium and calcium absorption were affected by changes in dietary wheat bran fibre and calcium, but not fat, in Fischer-344 rats when studied in a full factorial study which was a portion of a larger study of diet and colon carcinogenesis. For four weeks, nine-week-old rats were fed experimental purified diets to which had been added: wheat bran 0, 2.5 10, or 20%; fat 1, 5 or 10%; and calcium 0.

Serum gastrin increases with increasing dietary calcium but not with increasing dietary fat or fiber in Fischer-344 rats.

We studied the effects of dietary calcium, fat and fiber on serum gastrin in Fischer-344 rats in a full factorial experiment as part of a larger study of diet and colon cancer risk factors. Nine- to 10-wk-old male rats were fed standard or experimental diets for 4 wk. Wheat bran was the sole source of fiber.

Influence of microenvironmental pH on adriamycin resistance.

Resistance to Adriamycin (ADR) is frequently dependent upon enhanced efflux associated with the expression of the MDR1-encoded P membrane glycoprotein. Since enhanced expression of the MDR1 gene in ADR-resistant cells may be the result of spontaneous genetic mutation or amplification, it is presumed to be relatively stable and unalterable. Yet, reducing ADR efflux could increase sensitivity, and has been attempted using calcium channel blockers and other drugs.

Expression of surface antigens during the cell cycle in different growth phases of American and African Burkitt's lymphoma cell lines.

We have studied the expression of five surface antigens in eight Burkitt's lymphoma cell lines during different phases of the cell cycle and in different growth phases (logarithmic and stationary). Cells were stained simultaneously for surface antigens (fluorescein coupled antibodies) and DNA content (propidium iodide), and dual parameter measurements were performed with a flow cytometer. Analysis of cells in specific cell cycle phases during log-phase growth revealed a 1.

pH dependence of mitomycin C-induced cross-linking activity in EMT6 tumor cells.

Mitomycin C (MC), a quinone-containing bioreductive alkylating agent, is cytotoxic to aerobic EMT6 tumor cells despite the fact that little bioactivation of MC occurs in EMT6 cell homogenates in the presence of O2. Because spontaneous activation of MC at acidic pH has been reported in chemical systems, aerobic EMT6 tumor cells were incubated in serum-free 2-(N-morpholino)ethanesulfonic acid or N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid buffer at pH 5.7, 6.

A randomized trial to evaluate the immunorestorative properties of synthetic thymosin-alpha 1 in patients with lung cancer.

A randomized trial was performed in 42 postradiotherapy patients with non-small cell lung cancer to determine whether the administration of synthetic thymosin-alpha 1 by either a loading dose or a twice-weekly schedule could accelerate the reconstitution of thymic dependent immunity. The radiotherapy-induced immunosuppression was characterized by an absolute T cell lymphopenia and by impaired T cell function in lymphoproliferative assays. Placebo-treated patients did not show any improvement in T cell numbers or function over 15 weeks of serial immune monitoring, and exhibited gradual depressions of helper T lymphocyte percentages.

T-cell abnormalities after mediastinal irradiation for lung cancer. The in vitro influence of synthetic thymosin alpha-1.

The effects of mediastinal irradiation (RT) on the numbers and functions of purified peripheral blood T-lymphocytes from patients with locally advanced non-small cell lung cancer were evaluated. The patients were candidates for a randomized trial to evaluate the immunorestorative properties of synthetic thymosin alpha-1. Twenty-one patients studied before RT did not exhibit any significant difference in T-cell numbers or function compared to age-matched healthy subjects.

Phenotypic and ultrastructural characterization of a medullary thymocyte acute lymphoblastic leukemia with cellular procoagulant activity.

The phenotypic and ultrastructural characterization of the blast cells from a T-cell acute lymphoblastic leukemia (T-ALL) that was associated with disseminated intravascular coagulation (DIC) is described. The bone marrow blasts were considered to represent neoplastic medullary thymocytes and were acid phosphatase (+), terminal deoxynucleotidyl transferase (-), acid alpha-naphthyl acetate esterase (-), E-rosette (+) at 4 degrees C and 37 degrees C, Fc- and C3-receptor (-), and cALLA-, Ia-, 9.6+, OKT3+, OKT4+, OKT6+/-, OKT8+, OKT10+.

Inverse correlation between age related abnormalities of T-cell immunity and circulating thymosin alpha 1 levels in haemophilia A.

T-cell immunity and serum levels of thymosin alpha 1, beta 2-microglobulin, circulating immune complexes, serum immunoglobulin levels, antibodies to hepatitis surface or core antigen, and to cytomegalovirus, and Epstein-Barr virus were investigated in 51 patients with haemophilia A ranging in age from 2 to 52 years. All patients had received commercial U.S.