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Query: UMLS:C0432222 (SEM)
 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Bile acids are supposed to promote colonic cancer. In Crohn's disease, colonic carcinomas are relatively rare. We, therefore, compared ileal and right colonic mucosal bile acids analysed by gas-liquid chromatography in 8 patients with ileal Crohn's disease (14-48 yrs.) and 7 patients with right colonic carcinoma (28-77 yrs.) who underwent surgery. In both ileal and colonic mucosa, nonsulphated bile acid concentrations were somewhat higher in Crohn's disease (20.98 micrograms/g +/- 4.77 SEM; 12.09 micrograms/g +/- 2.55) than in colonic carcinoma (16.06 micrograms/g +/- 3.46; 7.75 micrograms/g +/- 4.28). In ileal mucosa, percentages of lithocholic and deoxycholic acids were slightly higher in colonic carcinoma (3.9%; 23.2%) than in Crohn's disease (1.1%; 14.9%). In colonic mucosa, carcinoma patients had more lithocholic (7.6%) and less deoxycholic acid (11.9%) than patients with Crohn's disease (1.7%; 20.3%). Bile acid sulphate esters were similar in both diseases (ca. 3.0 micrograms/g in ileal, 1.4 micrograms/g in colonic mucosa). Our results show that ileal and right colonic mucosal nonsulphated bile acids tend to be even lower in right colonic carcinoma than in Crohn's disease. This agrees well with our earlier findings of low mucosal bile acid concentrations in patients with left colonic carcinoma (Tokai J Exp Clin Med 8: 59-69, 1983) and does not support the assumption that bile acids are envolved in right colonic carcinogenesis.
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PMID:Ileal and colonic mucosal bile acids in Crohn's disease and right colonic carcinoma. 409 12

Zinc deficiency enhances experimental esophageal tumor induction. Vitamin A supplementation inhibits carcinogenesis in animals. Plasma zinc and plasma vitamin A levels are reduced in several human squamous cancers, but have not been studied in a US population with esophageal cancer. Therefore, we measured plasma zinc and vitamin A in patients with newly diagnosed esophageal cancer. In addition, we assessed hepatic and nutritional status and attempted to control for other factors known to influence plasma zinc and vitamin A levels. Plasma zinc and vitamin A were both significantly less in esophageal carcinoma than in age-matched healthy controls (plasma zinc 65.7 +/- 3.3 micrograms/dl [mean +/- SEM] in esophageal cancer versus 80.5 +/- 2.4 micrograms/dl in controls, P less than 0.01; plasma vitamin A 32.6 +/- 3.4 micrograms/dl in esophageal cancer versus 60.2 +/- 4.2 in controls, P less than 0.001). Overall, 15 of 17 patients with esophageal cancer had decreased plasma zinc and/or decreased plasma vitamin A. Our findings are compatible with a hypothesis that zinc or vitamin A deficiency may be co-factors in the induction of human esophageal carcinoma.
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PMID:Plasma zinc and vitamin A in human squamous carcinoma of the esophagus. 683 64

The most remarkable changes of human stomach, closely related to carcinogenesis are intestinal metaplasia. In order to define an interrelation between these mucosal changes and carcinogenesis, it seems to be necessary to study structural dynamics of normal and intestinalized gastric mucosa. We examined cell kinetics and morphological characteristics of human gastric mucosa, using 3H-thymidine autoradiography and scanning electron microscopic fractography. It is shown that in normal and fully developed intestinal metaplasia epithelial cells are regularly renewed within 15-60 days. A potential cancer cell, if it may appear in the otherwise normal mucosa, will be lost within this very short period of time. An experiment using hamsters confirmed this expectation. However, the situation is completely different when the gastric mucosa is in the process of intestinalization. Drastic rebuilding (Umbau) is taking place in dynamic structure of gastric gland. SEM fractography revealed this change in three-dimensional pictures. It is concluded that progression of the intestinalization keeps producing a large number of glandular fragments that are embedded in the depth of mucosa making the flow of the cellular turnover stagnant. It is inferred that the stagnation captures a potential cancer cell to make its propagation possible. Therefore, intestinalization can help the cancer cells to propagate in the body of the host. This role of the intestinal metaplasia explains many aspects of their "precancerous" characteristics.
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PMID:[Implication of the "precancerous lesions" in carcinogenesis of the stomach--a cytodynamic aspect]. 688 86

Transgenic mice carrying the bacterial lacl gene in a lambda shuttle vector were used to isolate and characterize background and 7,12-dimethylbenz[a]anthracene (DMBA)-induced mutations in skin. Adult male mice were treated once topically with either DMBA or acetone or were left untreated. Seven days later, DMBA treatment had significantly increased the mutant frequency in the skin (mean +/- SEM, 36 +/- 3 x 10(-5)) versus in vehicle-treated (6.4 +/- 1.2 x 10(-5)) and untreated mice (7.1 x 1.0 x 10(-5)). At least 10 mutants from each of three DMBA-treated and three untreated mice were selected for DNA sequence analysis. In each case, the entire 1080-bp target gene was sequenced. Base-pair substitutions predominated (86 of 96 mutations), although frameshift and deletion mutations were also detected. Twelve percent of the mutants carried more than one mutation. In controls, the mutations were predominantly GC-->AT transitions (26 of 42), and no AT-->TA transversions were recovered. In contrast, in the DMBA-treated mice, AT-->TA transversions represented 42% of the mutations (23 of 54) and GC-->AT transitions accounted for only 11%. The AT-->TA transversions occurred mostly at 5'-CA sites. This class of mutation has been recovered frequently in ras genes from DMBA-treated mice and probably represents an early event in carcinogenesis (Nelson MA et al., Proc Natl Acad Sci USA 89:6398-6402, 1992). Our present results are consistent with the types of DNA damage induced by DMBA. The observation of different mutant frequencies and spectra in treated and control mice demonstrates the utility of this approach in the study of mutagenesis in vivo.
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PMID:Mutational spectra in the lacl gene in skin from 7,12-dimethylbenz[a]anthracene-treated and untreated transgenic mice. 754 25

The effects of cycloheximide (CHX) and 2-[(aminopropyl)-amino]ethanethiol (WR-1065), each alone or in combination, on radiation-induced mutation induction at the hypoxanthine-guanine phosphoribosyl transferase (hprt) locus and cell killing were investigated using a Chinese hamster ovary (CHO) AA8 cell system. Treatment with CHX, a potent inhibitor of protein synthesis, at a concentration of 10 micrograms/ml administered 30 min prior to irradiation with 7.5 Gy had no effect on cell survival but did reduce the radiation-induced mutation frequency (per 10(6) survivors) from 106.5 +/- 8.8 (SEM) to 36.2 +/- 5.6 (SEM). Exposure of cells to 4 mM WR-1065 reduced the mutation frequency to 44.8 +/- 4.2 (SEM), but the combination of agents afforded no additional protection, that is 41.1 +/- 3.3 (SEM). The mechanism of action attributed to CHX in reducing mutation frequency is its ability to prevent the induction of an error-prone repair system. Split-dose radiation experiments, that is 8 Gy versus 4 Gy + 4 Gy separated by 3 h, were performed to evaluate and contrast the relative abilities of CHX and WR-1065, each alone or in combination, in affecting cell survival. Cycloheximide administered to cells 30 min before the first radiation dose and present throughout the 3 h incubation time prior to the second dose inhibited split-dose repair as evidence by a reduction in surviving fraction by 60% as compared with the value obtained for non-CHX-treated cells that were exposed to two equal doses of 4 Gy. Cells exposed to 4 mM WR-1065 immediately following the first 4 Gy radiation dose and then washed free 2.5 h before exposure to a second Gy dose, which was also followed by a 30 min exposure to WR-1065, increased the surviving fraction by 80% over the value obtained for cells not exposed to WR-1065 during their split-dose radiation treatment. When CHX treatment was combined with WR-1065 was abolished, that is surviving cell fraction was again reduced by approximately 60% as compared with untreated control groups. These results indicate that protein synthesis is required for WR-1065 to affect split-dose related repair processes. Presumably, the inhibition of the induction of an error-phone repair system by CHX would account for its effects on both resultant decreases in mutation frequency and cell survival. In contrast, WR-1065 and/or its disulfide metabolite appear to facilitate the efficacy and fidelity of such a repair system once it is induced.(ABSTRACT TRUNCATED AT 400 WORDS)
Carcinogenesis 1995 Nov
PMID:The effects of cycloheximide and WR-1065 on radiation-induced repair processes: a mechanism for chemoprevention. 758 89

The effect of different dietary carbohydrates (sucrose, cornstarch and high amylose cornstarch) on intestinal carcinogenesis was studied in male Sprague-Dawley rats treated subcutaneously with azoxymethane (AOM) at a weekly dose of 8 mg/kg body wt for 8 wk. The diets, high in fat and low in calcium and fiber, were fed during and after AOM treatment. The number of colonic adenomas per rat in the groups fed either starch was lower (P < 0.05) than the number in the sucrose-fed rats [1.06 +/- 0.38, 0.30 +/- 0.10 and 0.41 +/- 0.22 (mean +/- SEM), in the sucrose-, cornstarch- and high amylose cornstarch-fed groups, respectively]. The incidence of total intestinal tumors (adenomas + adenocarcinomas) was not affected by dietary treatment. However, the incidence of tumors in the small intestine of the rats fed the two cornstarch diets tended to be slightly lower than for rats fed the sucrose diet (P = 0.075). Adenoma dysplasia and adenocarcinoma differentiation were similar among the rats fed the three diets. However, the adenocarcinomas in the rats fed the cornstarch diet were significantly smaller than those in the rats fed sucrose [0.99 +/- 0.14 cm2 (n = 13), 0.56 +/- 0.14 cm2 (n = 13) and 0.55 +/- 0.17 cm2 (n = 9) in rats fed the sucrose, cornstarch and high amylose starch diets, respectively]. Moreover, in the rats fed the cornstarch diet, the adenocarcinomas showed lower invasive potential than those in rats fed the sucrose diet. The results suggest an overall inhibition of AOM-induced carcinogenesis in rats fed the cornstarch diets.
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PMID:Dietary carbohydrates modify azoxymethane-induced intestinal carcinogenesis in rats. 814 73

We have measured the levels of thymine glycol (TG) and thymidine glycol (dTG) in human urine, using an HPLC method. The results show that all 30 specimens examined (including 10 non-neoplastic and 20 neoplastic human urines) contained significant amounts of TG and dTG, average levels (mean +/- SEM) were 0.376 +/- 0.026 and 0.138 +/- 0.009 nmol/kg body weight/day respectively. The average levels of TG and dTG were 0.435 +/- 0.038 and 0.164 +/- 0.017 nmol/kg body weight/day in 10 healthy human urine specimens and 0.347 +/- 0.035 and 0.125 +/- 0.010 nmol/kg body weight/day in 20 neoplastic human urine specimens respectively. No significant differences were found between female and male as well as between the non-neoplastic and neoplastic human urine specimens. There were also wide interindividual variations, which were not age-dependent.
Carcinogenesis 1993 Jul
PMID:Oxidative damage to DNA: levels of thymine glycol and thymidine glycol in neoplastic human urines. 833 Mar 50

The association of refined sugars and colorectal cancers and polyps in three recent case-control studies led us to investigate the effects of sucrose, fructose and glucose on colonic epithelial proliferation and sensitivity to carcinogenesis. CF1 and C57BL/6J mice were used; proliferation was assessed as vincristine-accumulated mitotic figures per crypt section; sensitivity to carcinogenesis was assessed as the number of aberrant crypt foci (ACF) per colon observed following the colon carcinogen, azoxymethane (AOM, 3 mg/kg and 5 mg/kg). Oral gavages of sucrose and fructose in CF1 mice (10 g/kg) increased colonic proliferation 16 h later (2.8 +/- 0.6 and 4.1 +/- 0.7 (mean +/- SEM) accumulated mitotic figures/crypt section), compared with glucose and water (1.0 +/- 0.2 and 0.4 +/- 0.1). Sucrose and fructose given 14 h prior to the AOM (5 mg/kg) increased the sensitivity of the colon to carcinogenesis (18.4 +/- 1.5 and 13.1 +/- 1.8 ACF/colon), compared with glucose and water (11.4 +/- 2.0 and 8.6 +/- 1.1). Similar results were observed with C57BL/6J mice. We conclude that dietary sucrose and fructose may represent risk factors for colorectal cancer through a direct effect of the sugars on colonic epithelial proliferation.
Carcinogenesis 1993 Apr
PMID:Sucrose enhancement of the early steps of colon carcinogenesis in mice. 847 47

Quantitative analysis of lysozyme- and CD68-positive Kupffer cells was carried out in connection with diethylnitrosamine-induced hepatocarcinogenesis in non-human primates. The number of Kupffer cells/mm2 was determined in 28 cases of hepatocellular carcinoma (HCC) and seven age-matched controls. The Kupffer cell counts (mean +/-SEM) gradually decreased in the following order, irrespective of the histochemical markers (lysozyme or CD 68) used: healthy control liver (101.7 +/- 13.5 and 103.2 +/- 11.9 respectively), non-cirrhotic and non-neoplastic host liver (54.3 +/- 13.6 and 50.5 +/- 15.4), cirrhotic host liver (26.2 +/- 8.2 and 27.2 +/- 3.3), HCC tissue (20.7 +/- 4.4 and 19.3 +/- 4.1) and metastatic foci in the lung (9.8 +/- 1.8 and 9.7 +/- 2.8). The difference between the normal liver and the non-neoplastic, non-cirrhotic portions of the HCC-bearing liver was significant (P < 0.05). A highly significant difference was found between the number of Kupffer cells found in healthy control or non-neoplastic liver and those found in HCC nodules (P < 0.0001 and P < 0.0005 respectively). The results obtained by hematoxylin and eosin staining and lysozyme/CD68 immunohistochemistry were highly similar, indicating that this decrease was attributable primarily to numeric loss of Kupffer cells. The results suggest that the reduction in the number of Kupffer cells in HCC is a constant feature of hepatocarcinogenesis not only in rodent models, but also in non-human primates.
Carcinogenesis 1995 Dec
PMID:Quantitative evaluation of lysozyme- and CD68-positive Kupffer cells in diethylnitrosamine-induced hepatocellular carcinomas in monkeys. 860 89

Retinoids are biologic response modifiers that are present in normal skin and may possibly be perturbed in carcinogenesis. To examine this possibility in human skin, we analyzed vitamin A and cytosolic retinoid binding proteins (cellular retinol binding protein and cellular retinoic acid binding protein [CRABP]) in a total of 38 non-melanoma skin tumors and 25 healthy skin samples using high performance liquid chromatography, radioligand electrophoresis, and reverse transcriptase-polymerase chain reaction. The mean +/- SEM retinol concentration was normal in basal cell carcinoma (0.60 +/- 0.10 microM) and seborrheic keratosis (0.47 +/- 0.07 microM), but increased in keratoacanthoma (1.60 +/- 0.41 microM) and squamous cell carcinoma (1.17 +/- 0.28 microM) (p < 0.05 for both). Also, the concentrations of 3,4-didehydroretinol, a major vitamin A metabolite produced in human skin, were markedly elevated (6-7 times normal) in keratoacanthoma and squamous cell cancer. All types of tumors showed moderately increased levels of cellular retinol binding protein. In addition, keratoacanthoma and squamous cell cancer showed markedly increased levels (6-7 times normal) of CRABPII protein. Transcriptional activity of the CRABPII gene was demonstrated in both normal and neoplastic epidermis, but clear CRABPI mRNA expression was found only in basal cell carcinoma. The data indicate that characteristic perturbations of the vitamin A and retinoid binding protein levels occur in squamous cell-derived skin tumors, but whether these reflect intrinsic errors in retinoid metabolism or are secondary to abnormal cellular differentiation is unknown.
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PMID:Increased concentrations of 3,4-didehydroretinol and retinoic acid-binding protein (CRABPII) in human squamous cell carcinoma and keratoacanthoma but not in basal cell carcinoma of the skin. 861 41


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