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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Naturally occurring plant phenols with antimutagenic and anticarcinogenic activities were tested for their abilities to inhibit the biochemical and biological effects of the potent tumor promoter 12-O-tetradecanoyl-phorbol-13-acetate (TPA) in mouse epidermis in vivo. When applied topically to mouse skin, tannic acid (TA), ellagic acid, and several gallic acid derivatives all inhibit TPA-induced ornithine decarboxylase activity, hydroperoxide production, and DNA synthesis, three biochemical markers of skin tumor promotion. Moreover, in the two-step initiation-promotion protocol, the same phenolic compounds also inhibit the incidence and yield of skin tumors promoted by TPA. TA is the most effective of these treatments. Since they are already known to inhibit tumor initiation, the plant phenols protecting against skin tumor promotion by TPA may be universal inhibitors of multistage carcinogenesis. TA and other polyphenols, therefore, might be valuable in cancer therapy and/or prevention.
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PMID:Antitumor-promoting activities of tannic acid, ellagic acid, and several gallic acid derivatives in mouse skin. 141

Since it was first suggested that high dietary fat is a risk factor in colon cancer, there have been several studies to test this hypothesis. Epidemiologic studies suggested a positive association between dietary fat and colon cancer. Laboratory animal model studies demonstrated that not only the amount of fat, but also types of fat differing in fatty acid composition are important determining factors in colon tumor development. Chemically-induced colon tumor incidence was increased in rats fed the semipurified diets containing 23% corn oil, safflower oil, lard or beef tallow (high-fat) as compared to those fed 5% corn oil, safflower oil, lard or beef tallow diets (low-fat). Diets containing 23% coconut oil, olive oil or fish oil, or high-fat diets containing varying levels of trans fat, had no colon tumor-enhancing effect compared to their respective low fat diets. The stage at which the effect of dietary fat is exerted appears to be mostly during the post-initiation phase of colon carcinogenesis. Lack of a colon tumor enhancing effect of dietary fish oil is observed both during the initiation and postinitiation phases. The mechanisms by which various dietary fats increase colon carcinogenesis are not fully understood. In most instances, however, the high-fat diet appears to enhance tumorigenesis through elevation of agents, such as secondary bile acids, that act as promoters of tumor development. Lack of colon tumor promotion by dietary fish oil and trans fat appears to be mediated through their effect on mucosal ornithine decarboxylase activity, colonic secondary bile acids and/or prostaglandin synthesis.
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PMID:Dietary fat and colon cancer: animal model studies. 143

The development of tumorigenic conditions in the carcinogen-exposed rat colon was studied using selected morphological, histochemical, immunohistochemical and biochemical methods of analysis. Rats were treated with two carcinogens: 1,2-dimethylhydrazine and N-methyl-N'-nitro-N-nitrosoguanidine alone or with deoxycholic acid as a tumor promoter. It was found that 3 months after treatment of animals with the carcinogens the following changes were developed in colonic tissue: infiltration of lymphocytes in the mucous membrane, high increase in mitotic index among epithelial cells, negative reactions of colonic cells for neutral mucopolysaccharides and sulfomucins and positive reactions to carboxyl groups, nonsulfated acid mucosubstances and tissue polypeptide antigens. An increase in the activity of ornithine decarboxylase in colonic tissue was developed within the same time period and has been seen only in those tissues which were characterized by the development of precancerous conditions. Individual variations were observed in the manifestation of the studied parameters in rat neoplastic colonic tissues. It is suggested that these differences reflect an individual sensitivity of animals to carcinogens and the magnitude of the dysplastic processes induced in the colon.
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PMID:Individual variability of pathological parameters in chemically induced rat colon tumors. 144 80

Ultraviolet B radiation (UVB) and phorbol esters are known to promote tumor formation in skin; however, the interaction between UVB and phorbol esters in the regulation of gene expression remains incompletely understood. To define the interaction of UVB and phorbol esters in the control of keratinocyte gene expression, we have studied the effects of the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA) and UVB on the regulation of ornithine decarboxylase (ODC) gene expression in a rat keratinocyte cell line. Both UVB and TPA alone increased ODC activity and induced the expression of the ODC gene. The combination of UVB and TPA produced a further increment in ODC gene expression at 12 h, but UVB markedly attenuated the TPA induction of ODC mRNA transcripts at 3 h. Protein synthesis inhibition with cycloheximide also induced ODC mRNA transcripts, but did not eliminate the further induction of ODC gene expression by UVB or TPA. No changes in actin gene expression following exposure to TPA/UVB were detected in the same experiments. UVB and TPA alone or in combination had no effect on the transcriptional activity of an ODC-chloramphenicol acetyltransferase fusion gene in transfected rat keratinocytes. The results of these studies suggest a complex posttranscriptional interaction of phorbol esters and UVB in the control of keratinocyte gene expression.
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PMID:Interaction of TPA and ultraviolet B radiation in regulation of ODC gene expression in rat keratinocytes. 144 3

The mitogenic role of estradiol on the growth of colon cancer was examined in mice. Sham-operated or ovariectomized mice were injected with cancer cells and received estradiol treatment. Tumor growth was noted: tumor weights were higher in female than male mice. The growth of the tumors was least in ovariectomized mice and highest in estradiol-treated ovariectomized mice. Tumor messenger RNA (mRNA) levels for ornithine decarboxylase (ODC) and proto-oncogenes c-myc, c-fos, and H-ras were examined. Two transcripts (2.2 and 2.7 kilobase pairs) of ODC were observed. The steady-state mRNA levels for ODC paralleled the changes observed in the weight of the tumors in all groups of animals. Less dramatic changes were observed in c-myc mRNA levels. No significant differences were observed in the mRNA levels for H-ras and c-fos. It thus appears likely that an increase in the ODC mRNA levels and, to a lesser extent, an increase in c-myc mRNA levels may be some of the important mechanisms by which estradiol mediates its growth effects on colon cancer cells in vivo.
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PMID:Estradiol is trophic for colon cancer in mice: effect on ornithine decarboxylase and c-myc messenger RNA. 145 76

Our laboratory has been studying cancer chemopreventive effects of polyphenolic fraction isolated from green tea (GTP). In prior studies we have shown that (a) GTP possesses antigenotoxic effects in various test systems; (b) topical application of GTP protects against UV radiation and chemical carcinogen-induced tumorigenesis in murine skin; and (c) feeding of GTP in drinking water p.o. to mice protects against carcinogen-induced forestomach and lung tumorigenesis. Recently, we showed that in a dose-dependent manner GTP inhibits tumor promoter-caused induction of epidermal ornithine decarboxylase activity in SENCAR mice (R. Agarwal et al., Cancer Res., 52: 3582-3588, 1992). In the present study, we assessed the effect of GTP on TPA-induced skin tumor promotion in 7,12-dimethylbenz(a)anthracene-initiated SENCAR mouse. Topical application of varying doses of GTP (1-24 mg) 30 min prior to that of each TPA application resulted in highly significant protection against skin tumor promotion in a dose-dependent manner. The animals pretreated with GTP showed substantially lower tumor body burden such as decrease in total number of tumors per group, number of tumors per animal, tumor volume per mouse, and average volume per tumor, as compared to the animals that did not receive GTP. Since TPA-induced epidermal cyclooxygenase and lipoxygenase activities and edema and hyperplasia are conventionally used markers of skin tumor promotion, we also assessed the effect of preapplication of GTP on these parameters. As quantitated by the formation of prostaglandin and hydroxy-eicosatetraenoic acid metabolites from, respectively, cyclooxygenase- and lipoxygenase-catalyzed metabolism of arachidonic acid, skin application of GTP to SENCAR mice resulted in significant inhibition of TPA-caused effects on these 2 enzymes. Prior application of GTP to mouse skin also resulted in 30-46% inhibition of TPA-induced epidermal edema and hyperplasia. The results of the present study suggest that GTP possesses anti-skin tumor-promoting effects, and that the mechanism of such effects may involve inhibition of tumor promoter-induced epidermal ornithine decarboxylase, cyclooxygenase and lipoxygenase activities, edema, and hyperplasia. Further studies are in progress to define which component present in GTP is responsible for its anti-skin tumor-promoting effects.
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PMID:Inhibition of 12-O-tetradecanoylphorbol-13-acetate-caused tumor promotion in 7,12-dimethylbenz[a]anthracene-initiated SENCAR mouse skin by a polyphenolic fraction isolated from green tea. 145 78

The effects of palm carotene on chemical carcinogenesis was studied. Palm carotene suppressed mouse epidermal ornithine decarboxylase activity induced by glycocholic acid. In a two-stage mouse epidermal carcinogenesis experiment using 7,12-dimethylbenz(a)anthracene as the initiator, glycocholic acid as the 1st stage promoter, and mezerein as the 2nd stage promoter, palm carotene inhibited the promoting activity of glycocholic acid. Furthermore, in N-ethyl-N'-nitro-N-nitrosoguanidine-induced mouse duodenal carcinogenesis, 0.05% of palm carotene given in drinking water decreased the percentage of tumor-bearing mice significantly.
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PMID:Palm carotene inhibits tumor-promoting activity of bile acids and intestinal carcinogenesis. 146 91

Tumorigenesis requires increased biosynthesis of polyamines and elevated levels of ornithine decarboxylase, which is the rate-limiting enzyme in the polyamine synthesis pathway. Previous animal studies have noted a marked increase in ornithine decarboxylase after exposure to tumorigenic stimuli and that pretreatment with vitamins A and E provides protection against the carcinogenic action. However, studies of ornithine decarboxylase activity in human oral cavity carcinoma have not been as specific. The goal of this study was to determine whether a specific difference in ornithine decarboxylase activity occurs in tumor versus adjacent normal tissue in head and neck squamous cell carcinoma patients. Ornithine decarboxylase activity was measured in 30 consecutive head and neck cancer patients undergoing surgical therapy. Ornithine decarboxylase levels were found to be significantly elevated in tumor tissue samples when compared to adjacent normal mucosa samples (P less than .004). This finding confirms the previous findings noted in animal models and implies that the protective effects of vitamins A and E will extend to human head and neck cancers.
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PMID:Ornithine decarboxylase activity in tumor and normal tissue of head and neck cancer patients. 149 49

The term biologic marker (biomarker) of colorectal cancer refers in this article to an early preclinical phenotypic characteristic that relates to the risk for developing this cancer. Putative biologic markers in the normal colorectal mucosa of patients at risk include abnormal cell proliferation as determined by kinetic studies, ornithine decarboxylase activity, and polyamine synthesis. Alterations of mucin synthesis have been studied using both histochemical stains and lectin-binding techniques. Blood group and related carbohydrate antigens also have been evaluated as potential biomarkers in the normal mucosa. Biopsy small (less than 5 mm) polyps encountered at endoscopy has become a standard practice. Although a small polyp found to be an adenoma has a low likelihood of harboring high-grade dysplasia or invasive carcinoma, it represents an indicator of risk for colorectal neoplasia. Hyperplastic polyps, however, even though they have certain epidemiologic associations with colorectal neoplasia, are controversial as putative biomarkers of clinical relevance. Current research supports a concept of a field defect of the colorectal mucosa at risk for neoplasia, which may be identified by phenotypic abnormalities of the normal mucosa and the development of small adenomas.
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PMID:Precursors of colorectal carcinoma. Biopsy and biologic markers. 151 79

alpha-Difluoromethylornithine (DFMO), an inhibitor of ornithine decarboxylase, reduced intestinal lesions in tumor-bearing mice caused by treatment with N3-(3-methylbenzoyl)-3',5'-diacetyl [corrected]-FUDR (FF-705), a derivative of 5-fluoro-2'-deoxyuridine (FUDR). FF-705 at 32 mg/kg (the effective dose) suppressed tumor growth to about 40% of the control level. At this dose, body weight gain was suppressed slightly when FF-705 was given alone, and this change was milder in the DFMO-supplemented group. Intestinal lesions were suppressed almost completely by concomitant treatment with DFMO. The gross lesion index in the combined treatment group was similar to that in the controls and significantly smaller than in the FF-705-alone group (0.3 and 1.9, respectively). The histological lesion index in the combined treatment group was also significantly smaller than in the FF-705-alone group (7.9 and 23.8, respectively). When FF-705 was given at 64 mg/kg, the intestinal mucosal lesions were more severe, but DFMO supplementation reduced them by approximately 50%. Moreover, maltase and diamine oxidase activities of intestinal epithelium remained higher with combined treatment than with FF-705 alone. With FF-705 at 256 mg/kg (a toxic dose), DFMO had little protective effect against intestinal damage.
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PMID:Alleviation of intestinal lesions by combined treatment with a 5-fluoro-2'-deoxyuridine (FUDR) derivative and alpha-difluoromethylornithine (DFMO)[correction of DMFO] in tumor-bearing mice. 153 91


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