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Sample records for experimental colorectal carcinogenesis

  1. Colorectal carcinogenesis: Review of human and experimental animal studies

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    Tanaka Takuji

    2009-01-01

    Full Text Available This review gives a comprehensive overview of cancer development and links it to the current understanding of tumorigenesis and malignant progression in colorectal cancer. The focus is on human and murine colorectal carcinogenesis and the histogenesis of this malignant disorder. A summary of a model of colitis-associated colon tumorigenesis (an AOM/DSS model will also be presented. The earliest phases of colorectal oncogenesis occur in the normal mucosa, with a disorder of cell replication. The large majority of colorectal malignancies develop from an adenomatous polyp (adenoma. These can be defined as well-demarcated masses of epithelial dysplasia, with uncontrolled crypt cell proliferation. When neoplastic cells pass through the muscularis mucosa and infiltrate the submucosa, they are malignant. Carcinomas usually originate from pre-existing adenomas, but this does not imply that all polyps undergo malignant changes and does not exclude de novo oncogenesis. Besides adenomas, there are other types of pre-neoplasia, which include hyperplastic polyps, serrated adenomas, flat adenomas and dysplasia that occurs in the inflamed colon in associated with inflammatory bowel disease. Colorectal neoplasms cover a wide range of pre-malignant and malignant lesions, many of which can easily be removed during endoscopy if they are small. Colorectal neoplasms and/or pre-neoplasms can be prevented by interfering with the various steps of oncogenesis, which begins with uncontrolled epithelial cell replication, continues with the formation of adenomas and eventually evolves into malignancy. The knowledge described herein will help to reduce and prevent this malignancy, which is one of the most frequent neoplasms in some Western and developed countries.

  2. Colorectal Carcinogenesis: Role of Oxidative Stress and Antioxidants.

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    Carini, Francesco; Mazzola, Margherita; Rappa, Francesca; Jurjus, Abdo; Geagea, Alice Gerges; Al Kattar, Sahar; Bou-Assi, Tarek; Jurjus, Rosalyn; Damiani, Provvidenza; Leone, Angelo; Tomasello, Giovanni

    2017-09-01

    One of the contributory causes of colon cancer is the negative effect of reactive oxygen species on DNA repair mechanisms. Currently, there is a growing support for the concept that oxidative stress may be an important etiological factor for carcinogenesis. The purpose of this review is to elucidate the role of oxidative stress in promoting colorectal carcinogenesis and to highlight the potential protective role of antioxidants. Several studies have documented the importance of antioxidants in countering oxidative stress and preventing colorectal carcinogenesis. However, there are conflicting data in the literature concerning its proper use in humans, since these studies did not yield definitive results and were performed mostly in vitro on cell populations, or in vivo in experimental animal models. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  3. Preclinical Cancer Chemoprevention Studies Using Animal Model of Inflammation-Associated Colorectal Carcinogenesis

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    Tanaka, Takuji [Cytopatholgy Division, Tohkai Cytopathology Institute, Cancer Research and Prevention (TCI-CaRP), 5-1-2 Minami-uzura, Gifu 500-8285 (Japan); Department of Tumor Pathology, Gifu University Graduate School of Medicine, 1-1 Yanagido, Gifu 501-1194 (Japan)

    2012-07-16

    Inflammation is involved in all stages of carcinogenesis. Inflammatory bowel disease, such as ulcerative colitis and Crohn’s disease is a longstanding inflammatory disease of intestine with increased risk for colorectal cancer (CRC). Several molecular events involved in chronic inflammatory process are reported to contribute to multi-step carcinogenesis of CRC in the inflamed colon. They include over-production of free radicals, reactive oxygen and nitrogen species, up-regulation of inflammatory enzymes in arachidonic acid biosynthesis pathway, up-regulation of certain cytokines, and intestinal immune system dysfunction. In this article, firstly I briefly introduce our experimental animal models where colorectal neoplasms rapidly develop in the inflamed colorectum. Secondary, data on preclinical cancer chemoprevention studies of inflammation-associated colon carcinogenesis by morin, bezafibrate, and valproic acid, using this novel inflammation-related colorectal carcinogenesis model is described.

  4. Role of colonic microbiota in colorectal carcinogenesis: a systematic review

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    Marta Borges-Canha

    2015-11-01

    Full Text Available Background and aim: The human colonic mucosa is populated by a wide range of microorganisms, usually in a symbiotic relation with the host. Sometimes this balance is lost and a state of dysbiosis arises, exposing the colon to different metabolic and inflammatory stimuli (according to the microbiota's changing profile. Recent findings lead to hypothesize that this unbalance may create a subclinical pro-inflammatory state that increases DNA mutations and, therefore, colorectal carcinogenesis. In this article we aim to systematically review the scientific evidence regarding colonic microbiota and its role in colorectal carcinogenesis. Methods: Systematic review of PubMed searching results for original articles studying microbiota and colorectal cancer until November 2014. Results: Thirty-one original articles studied the role of colon microbiota in colorectal carcinoma including both human and animal studies. Different and heterogeneous methods were used and different bacteria were considered. Nevertheless, some bacteria are consistently augmented (such as Fusobacteria, Alistipes, Porphyromonadaceae, Coriobacteridae, Staphylococcaceae, Akkermansia spp. and Methanobacteriales, while other are constantly diminished in colorectal cancer (such as Bifidobacterium, Lactobacillus, Ruminococcus, Faecalibacterium spp., Roseburia, and Treponema. Moreover, bacteria metabolites amino acids are increased and butyrate is decreased throughout colonic carcinogenesis. Conclusion: Conclusive evidence shows that colorectal carcinogenesis is associated with microbial dysbiosis. This information may be used to create new prophylactic, diagnostic and therapeutic strategies for colorectal cancer.

  5. Ghrelin administration suppresses inflammation-associated colorectal carcinogenesis in mice.

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    Kawaguchi, Makiko; Kanemaru, Ai; Fukushima, Tsuyoshi; Yamamoto, Koji; Tanaka, Hiroyuki; Haruyama, Yukihiro; Itoh, Hiroshi; Matsumoto, Nobuhiro; Kangawa, Kenji; Nakazato, Masamitsu; Kataoka, Hiroaki

    2015-09-01

    Ghrelin is a 28-amino-acid peptide that stimulates the release of pituitary growth hormone. Because of its orexigenic effects, ghrelin is being developed as a therapeutic option for postoperative support and treatment of anorexia-cachexia syndrome of cancer patients. However, ghrelin has a multiplicity of physiological functions, and it also affects cell proliferation. Therefore, the effects of ghrelin administration on carcinogenesis and cancer progression in patients susceptible to cancer should be clarified. In this study, we examined the effects of ghrelin on cancer promotion in vivo using murine intestinal carcinogenesis models. Intestinal tumorigenesis was examined to determine the effects of either exogenous ghrelin administration or ghrelin deficiency following deletion of the Ghrl gene. Two murine intestinal tumorigenesis models were used. The first was the azoxymethane (AOM)/dextran sodium sulfate (DSS)-induced inflammation-associated colon carcinogenesis model and the second was the Apc(Min/+) genetic cancer susceptibility model. In AOM/DSS-treated mice, administration of ghrelin significantly suppressed tumor formation in the colon. In contrast, ghrelin administration did not affect the number of intestinal tumors formed in Apc(Min/+) mice. The absence of endogenous ghrelin did not affect the incidence of intestinal tumors in either AOM/DSS-treated mice or Apc(Min/+) mice, though tumor size tended to be larger in Ghrl(-/-) colons in the AOM/DSS model. No tumor-promoting effect was observed by ghrelin administration in either tumorigenesis model. In summary, this study provides in vivo experimental evidence for the usefulness of ghrelin administration in the chemoprevention of inflammation-associated colorectal carcinogenesis and may suggest its safety in patients under colitis-associated cancer susceptibility conditions. © 2015 The Authors. Cancer Science published by Wiley Publishing Asia Pty Ltd on behalf of Japanese Cancer Association.

  6. Beclin 1 Expression is Closely Linked to Colorectal Carcinogenesis and Distant Metastasis of Colorectal Carcinoma

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    Mei-Ying Zhang

    2014-08-01

    Full Text Available Beclin 1 participates in development, autophagy, differentiation, anti- apoptosis, neurodegeneration, tumorigenesis and cancer progression. The roles of Beclin 1 in colorectal carcinogenesis and its subsequent progression are still unclear. Here, the mRNA and protein expression of Beclin 1 were determined in colorectal carcinoma and matched mucosa by Reverse transcriptase-polymerase chain reaction and Western blot. Immunohistochemistry and in situ hybridization (ISH were performed on tissue microarryer with colorectal carcinoma, adenoma and mucosa. The expression of Beclin 1 mRNA and protein was found to be higher in colorectal carcinoma than matched mucosa by real-time PCR and Western blot (p < 0.05. According to the ISH data, Beclin 1 expression was lower in colorectal non-neoplastic mucosa (NNM than adenoma and carcinoma (p < 0.05. Immunohistochemically, primary carcinoma showed stronger Beclin 1 expression than NNM and metastatic carcinoma in the liver (p < 0.05. Beclin 1 protein expression was negatively related to liver and distant metastasis (p < 0.05, but not correlated with age, sex, depth of invasion, lymphatic or venous invasion, lymph node metastasis, tumor-node-metastasis (TNM staging, differentiation or serum carcinoembryonic antigen (CEA concentration (p > 0.05. Survival analysis indicated that Beclin 1 expression was not linked to favorable prognosis of the patients with colorectal carcinoma (p > 0.05. Cox’s model indicated that depth of invasion and distant metastasis were independent prognostic factors for colorectal carcinomas (p < 0.05. It was suggested that Beclin 1 expression is closely linked to colorectal carcinogenesis and distant metastasis of colorectal carcinoma.

  7. The role of B-vitamins - gene interactions in colorectal carcinogenesis: A molecular epidemiological approach

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    Donk, van den M.

    2005-01-01

    Folate deficiency can affect DNA methylation and DNA synthesis. Both factors may be operative in colorectal carcinogenesis. Many enzymes, like methylenetetrahydrofolate reductase (MTHFR), thymidylate synthase (TS), methionine synthase (MTR), and serine hydroxymethyltransferase (SHMT), are needed for

  8. Oral concentrated grape juice suppresses expression of NF-kappa B, TNF-α and iNOS in experimentally induced colorectal carcinogenesis in Wistar rats.

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    Campanholo, Vanessa Maria de Lima Pazine; Silva, Roseane Mendes; Silva, Tiago Donizetti; Neto, Ricardo Artigiani; Paiotti, Ana Paula Ribeiro; Ribeiro, Daniel Araki; Forones, Nora Manoukian

    2015-01-01

    The aim of this study was to evaluate the effects of grape juice on colon carcinogenesis induced by azoxymethane (AOM) and expression of NF-kB, iNOS and TNF- α. Forty male Wistar rats were divided into 7 groups: G1, control; G2, 15 mg/kg AOM; G3, 1% grape juice 2 weeks before AOM; G4, 2% grape juice 2 weeks before AOM; G5, 1% grape juice 4 weeks after AOM; G6, 2% grape juice 4 weeks after AOM; G7, 2% grape juice without AOM. Histological changes and aberrant crypt foci (ACF) were studied, while RNA expression of NF- kB, TNF- and iNOS was evaluated by qPCR. The number of ACF was higher in G2, and G4 presented a smaller number of crypts per focus than G5 (p=0.009) and G6. Small ACF (1-3) were more frequent in G4 compared to G2, G5 and G6 (p=0.009, p=0.009 and p=0.041, respectively). RNA expression of NF-kB was lower in G3 and G4 compared to G2 (p=0.004 and p=0.002, respectively). A positive correlation was observed between TNF- α and NF-kB gene expression (p=0.002). In conclusion, the administration of 2% grape juice before AOM reduced the crypt multiplicity, attenuating carcinogenesis. Lower expression of NF-kB was observed in animals exposed to grape juice for a longer period of time, regardless of concentration.

  9. Role of gastrin-peptides in Barrett's and colorectal carcinogenesis.

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    Chueca, Eduardo; Lanas, Angel; Piazuelo, Elena

    2012-12-07

    Gastrin is the main hormone responsible for the stimulation of gastric acid secretion; in addition, gastrin and its derivatives exert proliferative and antiapoptotic effects on several cell types. Gastrin synthesis and secretion are increased in certain situations, for example, when proton pump inhibitors are used. The impact of sustained hypergastrinemia is currently being investigated. In vitro experiments and animal models have shown that prolonged hypergastrinemia may be related with higher cancer rates; although, this relationship is less clear in human beings. Higher gastrin levels have been shown to cause hyperplasia of several cell types; yet, the risk for developing cancer seems to be the same in normo- and hypergastrinemic patients. Some tumors also produce their own gastrin, which can act in an autocrine manner promoting tumor growth. Certain cancers are extremely dependent on gastrin to proliferate. Initial research focused only on the effects of amidated gastrins, but there has been an interest in intermediates of gastrin in the last few decades. These intermediates aren't biologically inactive; in fact, they may exert greater effects on proliferation and apoptosis than the completely processed forms. In certain gastrin overproduction states, they are the most abundant gastrin peptides secreted. The purpose of this review is to examine the gastrin biosynthesis process and to summarize the results from different studies evaluating the production, levels, and effects of the main forms of gastrin in different overexpression states and their possible relationship with Barrett's and colorectal carcinogenesis.

  10. Cimetidine and Clobenpropit Attenuate Inflammation-Associated Colorectal Carcinogenesis in Male ICR Mice

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    Takuji Tanaka

    2016-02-01

    Full Text Available Histamine and histamine receptors (Hrhs have been identified as critical molecules during inflammation and carcinogenesis. This study was conducted to determine the effects of Hrh1-Hrh3 antagonists on inflammation-associated colorectal carcinogenesis. Male ICR mice were treated with azoxymethane (AOM, 10 mg/kg bw, i.p. and 1.5% dextran sodium sulfate (DSS, drinking water for 7 days to induce colorectal carcinogenesis. The mice were then fed diets containing test chemical (500 ppm terfenadine, 500 ppm cimetidine or 10 ppm clobenpropit for 15 weeks. At week 18, feeding with the diets containing cimetidine (Hrh2 antagonist and clobenpropit (Hrh3 antagonist/inverse agonist significantly lowered the multiplicity of colonic adenocarcinoma. Terfenadine (Hrh1 antagonist did not affect AOM-DSS-induced colorectal carcinogenesis. Adenocarcinoma cells immunohistochemically expressed Hrh1, Hrh2, Hrh3 and Hrh4 with varied intensities. Because clobenpropit is also known to be a Hrh4 receptor agonist, Hrh2, Hrh3 and Hrh4 may be involved in inflammation-related colorectal carcinogenesis. Additional data, including the mRNA expression of pro-inflammatory cytokines and inducible inflammatory enzymes in the colonic mucosa, are also presented.

  11. Genomic lesions and colorectal carcinogenesis: the effects of protein-calorie restriction and inulin supplementation on deficiency statuses.

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    Cantero, W B; Takahachi, N A; Mauro, M O; Pesarini, J R; Rabacow, A P M; Antoniolli, A C M B; Oliveira, R J

    2015-03-27

    The present study investigated the effects of restricting protein and calories and supplementation of inulin, a fiber comprising a linear type of polydisperse carbohydrates composed primarily of fructil-fructose bonds (β-(2→1), on the deficiency statuses of animals in which genomic lesion development and colorectal carcinogenesis had been induced. This experiment involved adult male Swiss mice (N = 11/group). The experimental groups were as follows: Negative Control (vehicle), Positive Control, 1,2-dimethylhydrazine (DMH), Inulin, and Associate. DMH, which promoted colorectal cancer, was administered intraperitoneally in 4 20-mg/kg body weight (bw) doses during a 2-week period; inulin was administered orally at a daily dose of 50 mg/kg bw. Each group was bifurcated; half of each group was fed a normal protein diet and the other half was fed a low-protein diet. The results indicated that a correlation existed between malnutrition and an increased frequency of genomic lesions but that malnutrition did not predispose animals to colorectal cancer development. Inulin exhibited genotoxic activity, which requires further investigation, and low anti-genotoxic activity. Moreover, inulin reduced the levels of intestinal carcinogenesis biomarkers in both malnourished and healthy animals. These data suggest that inulin holds therapeutic potential and is a strong candidate for inclusion among the functional foods used for cancer prevention in both properly nourished and malnourished individuals.

  12. Ghrelin administration suppresses inflammation-associated colorectal carcinogenesis in mice

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    Kawaguchi, Makiko; Kanemaru, Ai; FUKUSHIMA, Tsuyoshi; Yamamoto, Koji; Tanaka, Hiroyuki; Haruyama, Yukihiro; Itoh, Hiroshi; MATSUMOTO, Nobuhiro; Kangawa, Kenji; Nakazato, Masamitsu; Kataoka, Hiroaki

    2015-01-01

    Ghrelin is a 28-amino-acid peptide that stimulates the release of pituitary growth hormone. Because of its orexigenic effects, ghrelin is being developed as a therapeutic option for postoperative support and treatment of anorexia-cachexia syndrome of cancer patients. However, ghrelin has a multiplicity of physiological functions, and it also affects cell proliferation. Therefore, the effects of ghrelin administration on carcinogenesis and cancer progression in patients susceptible to cancer s...

  13. Collagen mRNA levels changes during colorectal cancer carcinogenesis

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    Skovbjerg, Hanne; Anthonsen, Dorit; Lothe, Inger M B

    2009-01-01

    . In addition, corresponding tissue was examined from healthy volunteers (n = 20). mRNA levels were normalized to beta-actin. Immunohistochemical analysis of the distributions of type IV and type VII collagens were performed on normal and affected tissues from colorectal cancer patients. RESULTS: The alpha1(IV......). The level of alpha 6(IV) was 5-fold lower in colorectal cancer tissue as compared to healthy individuals (p alpha 6(IV) mRNA coincides...... zone of stratified epithelia. Immunohistochemical studies have previously reported changes in steady-state levels of different alpha(IV) chains in several epithelial cancer types. In the present study we aimed to quantitatively determine the mRNA levels of type IV collagen (alpha1/alpha 4/alpha 6...

  14. Different Susceptibilities between Apoe- and Ldlr-Deficient Mice to Inflammation-Associated Colorectal Carcinogenesis

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    Takuji Tanaka

    2016-10-01

    Full Text Available Hypercholesterolemia resulting in atherosclerosis is associated with an increased risk of ischemic heart disease and colorectal cancer (CRC. However, the roles of apoliprotein (Apo E (Apoe and low-density lipoprotein (Ldl receptor (Ldlr in colorectal carcinogenesis have not yet been investigated. In this study, we examined the susceptibility of Apoe-deficient and Ldlr-deficient mice, which are genetic animal models of atherosclerosis to azoxymethane (AOM/dextran sodium sulfate (DSS-induced colorectal carcinogenesis. In Experiment 1, male Apoe-deficient (n = 20 and wild type (WT mice (C57BL/6J, n = 21 were treated with a single intraperitoneal (i.p. injection of AOM (10 mg/kg body weight and then given 1.5% DSS in drinking water for seven days. They were maintained up to week 20 and sacrificed for the histopathological examination of colorectal tumors. The mRNA expression of cyclooxygenase (Cox-2, inducible nitric oxide synthase (Nos2, tumor necrosis factor (Tnf-α interleukin (Il-1β, and Il-6 was assayed in the colorectal mucosa. In Experiment 2, male Ldlr-deficient (n = 14 and WT mice (C57BL/6J, n = 10 were given a single i.p. injection of AOM (10 mg/kg body weight and then given 2% DSS in drinking water for seven days. They were sacrificed at week 20 to evaluate their colorectum histopathologically. In Experiment 1, the multiplicity of CRCs was significantly higher in the Apoe-deficient mice (2.75 ± 1.48 than in the WT mice (0.62 ± 0.67. The serum lipoprotein levels in the Apoe-deficient mice were also significantly higher than in the WT mice. In Experiment 2, the incidence (29% and multiplicity (0.50 ± 0.94 of CRCs in the Ldlr mice were significantly lower than in the WT mice (80% incidence and 3.10 ± 2.38 multiplicity. The mRNA expression of two inducible enzymes and certain pro-inflammatory cytokines in the colorectum of each genotype was greater than in the respective WT mice. The values in the Apoe-deficient mice were much greater

  15. Chemopreventive Effects of Eryngium foetidum L. Leaves on COX-2 Reduction in Mice Induced Colorectal Carcinogenesis.

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    Promtes, Kamonwan; Kupradinun, Piengchai; Rungsipipat, Anudep; Tuntipopipat, Siriporn; Butryee, Chaniphun

    2016-01-01

    To investigate the potential effects of Eryngium foetidum Linn. leaves (EF) in colitis-induced colorectal carcinogenesis in mice by azoxymethane (AOM) and dextran sulfate sodium (DSS), 39 ICR male mice were studied and divided into 6 groups. The mice were received a modified AIN-76 diet in Group 1, whereas Group 2 was given an AOM, DSS, and AIN-76 diet. Groups 3 and 4 were fed with 0.8% and 3.2% freeze-dried EF with AIN-76 diets, for 5 wk. Groups 5 and 6 were fed with 0.8% and 3.2% EF diets for 5 wk during AOM/DSS administration. The mice were necropsied at Week 20 and their colons were collected. The results indicated that the incidences of tumors in Groups 2, 5, and 6 was 100%, 75%, and 88%, with multiplicities (mean ±SE) of 3.75 ±0.92, 2.38 ± 0.96 and 4.25 ± 0.79, respectively. Interestingly, there was a significant difference in COX-2 expression in mice received 3.2% EF in their diet, but the proliferative cell nuclear antigen index and iNOS protein expression were not significantly different. We concluded that EF at a dose level of 3.2% in their diet had a preventive effect on colorectal carcinogenesis via the proinflammatory cytokine, COX-2.

  16. Nutraceutical Approach for Preventing Obesity-Related Colorectal and Liver Carcinogenesis

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    Hisataka Moriwaki

    2012-01-01

    Full Text Available Obesity and its related metabolic abnormalities, including insulin resistance, alterations in the insulin-like growth factor-1 (IGF-1/IGF-1 receptor (IGF-1R axis, and the state of chronic inflammation, increase the risk of colorectal cancer (CRC and hepatocellular carcinoma (HCC. However, these findings also indicate that the metabolic disorders caused by obesity might be effective targets to prevent the development of CRC and HCC in obese individuals. Green tea catechins (GTCs possess anticancer and chemopreventive properties against cancer in various organs, including the colorectum and liver. GTCs have also been known to exert anti-obesity, antidiabetic, and anti-inflammatory effects, indicating that GTCs might be useful for the prevention of obesity-associated colorectal and liver carcinogenesis. Further, branched-chain amino acids (BCAA, which improve protein malnutrition and prevent progressive hepatic failure in patients with chronic liver diseases, might be also effective for the suppression of obesity-related carcinogenesis because oral supplementation with BCAA reduces the risk of HCC in obese cirrhotic patients. BCAA shows these beneficial effects because they can improve insulin resistance. Here, we review the detailed relationship between metabolic abnormalities and the development of CRC and HCC. We also review evidence, especially that based on our basic and clinical research using GTCs and BCAA, which indicates that targeting metabolic abnormalities by either pharmaceutical or nutritional intervention may be an effective strategy to prevent the development of CRC and HCC in obese individuals.

  17. Dietary Crocin Inhibits Colitis and Colitis-Associated Colorectal Carcinogenesis in Male ICR Mice

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    Kunihiro Kawabata

    2012-01-01

    Full Text Available A natural carotenoid crocin is contained in saffron and gardenia flowers (crocuses and gardenias and is used as a food colorant. This study reports the potential inhibitory effects of crocin against inflammation-associated mouse colon carcinogenesis and chemically induced colitis in male ICR mice. In the first experiment, dietary crocin significantly inhibited the development of colonic adenocarcinomas induced by azoxymethane (AOM and dextran sodium sulfate (DSS in mice by week 18. Crocin feeding also suppressed the proliferation and immunohistochemical expression of nuclear factor- (NF- κB but increased the NF-E2-related factor 2 (Nrf2 expression, in adenocarcinoma cells. In the second experiment, dietary feeding with crocin for 4 weeks was able to inhibit DSS-induced colitis and decrease the mRNA expression of tumor necrosis factor α, interleukin- (IL- 1β, IL-6, interferon γ, NF-κB, cyclooxygenase-2, and inducible nitric oxide synthase in the colorectal mucosa and increased the Nrf2 mRNA expression. Our results suggest that dietary crocin suppresses chemically induced colitis and colitis-related colon carcinogenesis in mice, at least partly by inhibiting inflammation and the mRNA expression of certain proinflammatory cytokines and inducible inflammatory enzymes. Therefore, crocin is a candidate for the prevention of colitis and inflammation-associated colon carcinogenesis.

  18. Kimchi protects against azoxymethane/dextran sulfate sodium-induced colorectal carcinogenesis in mice.

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    Kim, Hee-Young; Song, Jia-Le; Chang, Hee-Kyung; Kang, Soon-Ah; Park, Kun-Young

    2014-08-01

    The chemopreventive effects of different types and quantities of kimchi prepared with different subingredients, including commercial kimchi (CK), standardized kimchi (SK), cancer-preventive kimchi (CPK), and anticancer kimchi (ACK), on colorectal carcinogenesis in mice were evaluated. The development of colon cancer was induced in male BALB/c mice with a single intraperitoneal injection of azoxymethane (AOM, 10 mg/kg body weight) and subsequent treatment with 2% dextran sulfate sodium (DSS) in drinking water for 7 days for two cycles. After exposure to AOM and DSS, treatment with the methanolic extracts from different kimchis, particularly 1.89 g/kg of ACK, significantly increased colon length, decreased the ratio of colon weight/length, and resulted in the lowest number of tumors compared with the other kimchi-treated groups. Histological observation revealed that ACK was able to suppress AOM- and DSS-induced colonic mucosal damage and neoplasia. ACK also significantly decreased the mRNA levels of proinflammatory cytokines (TNF-α, IL-6, and IFN-γ) as well as the mRNA and protein expression of inducible nitric oxide synthase and cyclooxygenase-2 (COX-2). In addition, the mRNA and protein expression of p53 and p21 was elevated in colon tissues from the ACK-treated mice compared with the other kimchi-treated groups. Our results suggest that kimchi exerted a suppressive effect on AOM- and DSS-induced colorectal carcinogenesis in the BALB/c mice. The anticancer effects of ACK were particularly potent. Thus, it is possible that the health-promoting subingredients added to ACK might be used to prevent colon carcinogenesis in humans.

  19. Kimchi Protects Against Azoxymethane/Dextran Sulfate Sodium–Induced Colorectal Carcinogenesis in Mice

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    Kim, Hee-Young; Song, Jia-Le; Chang, Hee-Kyung; Kang, Soon-Ah

    2014-01-01

    Abstract The chemopreventive effects of different types and quantities of kimchi prepared with different subingredients, including commercial kimchi (CK), standardized kimchi (SK), cancer-preventive kimchi (CPK), and anticancer kimchi (ACK), on colorectal carcinogenesis in mice were evaluated. The development of colon cancer was induced in male BALB/c mice with a single intraperitoneal injection of azoxymethane (AOM, 10 mg/kg body weight) and subsequent treatment with 2% dextran sulfate sodium (DSS) in drinking water for 7 days for two cycles. After exposure to AOM and DSS, treatment with the methanolic extracts from different kimchis, particularly 1.89 g/kg of ACK, significantly increased colon length, decreased the ratio of colon weight/length, and resulted in the lowest number of tumors compared with the other kimchi-treated groups. Histological observation revealed that ACK was able to suppress AOM- and DSS-induced colonic mucosal damage and neoplasia. ACK also significantly decreased the mRNA levels of proinflammatory cytokines (TNF-α, IL-6, and IFN-γ) as well as the mRNA and protein expression of inducible nitric oxide synthase and cyclooxygenase-2 (COX-2). In addition, the mRNA and protein expression of p53 and p21 was elevated in colon tissues from the ACK-treated mice compared with the other kimchi-treated groups. Our results suggest that kimchi exerted a suppressive effect on AOM- and DSS-induced colorectal carcinogenesis in the BALB/c mice. The anticancer effects of ACK were particularly potent. Thus, it is possible that the health-promoting subingredients added to ACK might be used to prevent colon carcinogenesis in humans. PMID:25029638

  20. Genetic characteristics of mitochondrial DNA was associated with colorectal carcinogenesis and its prognosis.

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    Jae-Ho Lee

    Full Text Available Clinical value of mitochondrial DNA has been described in colorectal cancer (CRC. To clarify its role in colorectal carcinogenesis, mitochondrial microsatellite instability (mtMSI and other markers were investigated in CRCs and their precancerous lesions, as a multitier genetic study. DNA was isolated from paired normal and tumoral tissues in 78 tubular adenomas (TAs, 34 serrated polyps (SPs, and 100 CRCs. mtMSI, nucleus microsatellite instability (nMSI, KRAS mutation, and BRAF mutation were investigated in these tumors and their statistical analysis was performed. mtMSI was found in 30% of CRCs and 21.4% of precancerous lesions. Mitochondrial copy number was higher in SPs than TAs and it was associated with mtMSI in low grade TAs. KRAS and BRAF mutations were mutually exclusive in TAs and SPs. CRCs with mtMSI showed shorter overall survival times than the patients without mtMSI. In CRCs without nMSI or BRAF mutation, mtMSI was a more accurate marker for predicting prognosis. The genetic change of mitochondrial DNA is an early and independent event in colorectal precancerous lesions and mtMSI and mitochondrial contents are associated with the tubular adenoma-carcinoma sequence, resulting in poor prognosis. This result suggested that the genetic change in mitochondrial DNA appears to be a possible prognosis marker in CRC.

  1. Independent Induction of Caspase-8 and cFLIP Expression during Colorectal Carcinogenesis in Sporadic and HNPCC Adenomas and Carcinomas

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    D. M. Heijink

    2007-01-01

    Full Text Available Background: TNF-Related Apoptosis Inducing Ligand (TRAIL is a promising agent for the induction of apoptosis in neoplastic tissues. Important determinants of TRAIL sensitivity are two intracellular proteins of the TRAIL pathway, caspase-8 and its anti-apoptotic competitor cellular Flice-Like Inhibitory Protein (cFLIP. Methods: The aim of this study was to investigate basic expression of caspase-8 and cFLIP in normal colorectal epithelium (n = 20, colorectal adenomas (n = 66 and colorectal carcinomas (n = 44 using immunohistochemistry performed on both sporadic and Hereditary Non-Polyposis Colorectal Cancer (HNPCC or Lynch syndrome-associated adenomas and carcinomas. Results: Expression of both caspase-8 and cFLIP was similar in cases with sporadic and hereditary origin. Expression of caspase-8 in colorectal adenomas and carcinomas was increased when compared to normal colon tissue (P = 0.02. Nuclear, paranuclear as well as cytoplasmic localizations of caspase-8 were detected. Immunohistochemistry revealed an upregulation of cFLIP in colorectal carcinomas in comparison to normal epithelium and colorectal adenomas (P < 0.001. A large variation in the caspase-8/cFLIP ratio was observed between the individual adenomas and carcinomas. Conclusion: Caspase-8 and cFLIP are upregulated during colorectal carcinogenesis. Upregulation of caspase-8 and/or downregulation of cFLIP may be interesting approaches to maximize TRAIL sensitivity in colorectal neoplasms.

  2. A critical overview on the biological and molecular features of red and processed meat in colorectal carcinogenesis.

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    Jeyakumar, Arunan; Dissabandara, Lakal; Gopalan, Vinod

    2017-04-01

    A recent investigation by the World Health Organisation (WHO) has found that the consumption of processed meat and potentially red meat promotes carcinogenesis and can increase the risk of colorectal cancer. This literature review aims to summarise both the red and processed meat molecules associated with colorectal carcinogenesis and investigate their relationship with the pathogenic process of colorectal cancer. Literature relating to the carcinogenic effect of red and processed meat molecules was critically reviewed. There are multiple molecules present in red and processed meat with a potential carcinogenic effect on colorectal tissues. Processed meat is more carcinogenic compared to red meat because of the abundance of potent nitrosyl-heme molecules that form N-nitroso compounds. Studies have also noted that other molecules such as polycyclic aromatic hydrocarbons and heterocyclic amines have potential mechanisms for the initiation of colorectal cancer pathogenesis. The non-human sugar molecule N-glycolylneuraminic acid may account for the carcinogenic effects of pork despite its heme content being comparable to that of chicken. Red meat products, especially those that have been processed, have a wide variety of carcinogenic molecules known to increase the risk of colorectal cancer. Thus, the outcome of this review is consistent with the recent findings of WHO.

  3. Thymus in experimental carcinogenesis of the prostate gland.

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    Borodin, Yu I; Lomshakov, A A; Astashov, V V; Kazakov, O V; Mayorov, A P; Larionov, P M

    2014-10-01

    We studied structural changes in the prostate gland, thymus, and lymph nodes in CBA mice after transplantation of Ehrlich ascites tumor cells into the prostate gland. On experimental day 5, the number of blood and lymph vessels decreased in the gland; the percentage of connective tissue elements and glandular tissue and the number of immunoblasts in the thymus increased. On day 18, the number of blood vessels in the tumor decreased; the width of the cortex and glandular tissue increased in the thymus, while the number of immunoblasts was reduced. On day 28, tumor infiltration and increased number of lymphatic vessels in its stroma were observed; parenchyma was reduced, and the area of the connective tissue increased in the thymus. These structural changes indicated the development of accidental involution of the thymus during carcinogenesis of the prostate.

  4. Development of an Inflammation-Associated Colorectal Cancer Model and Its Application for Research on Carcinogenesis and Chemoprevention

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    Takuji Tanaka

    2012-01-01

    Full Text Available Chronic inflammation is a well-recognized risk factor for development of human cancer in several tissues, including large bowel. Inflammatory bowel disease, including ulcerative colitis and Crohn’s disease, is a longstanding inflammatory disease of intestine with increased risk for colorectal cancer development. Several molecular events involved in chronic inflammatory process may contribute to multistep carcinogenesis of human colorectal cancer in the inflamed colon. They include overproduction of reactive oxygen and nitrogen species, overproduction and upregulation of productions and enzymes of arachidonic acid biosynthesis pathway and cytokines, and intestinal immune system dysfunction. In this paper, I will describe several methods to induce colorectal neoplasm in the inflamed colon. First, I will introduce a protocol of a novel inflammation-associated colon carcinogenesis in mice. In addition, powerful tumor-promotion/progression activity of dextran sodium sulfate in the large bowel of ApcMin/+ mice will be described. Finally, chemoprevention of inflammation-associated colon carcinogenesis will be mentioned.

  5. Low ABCB1 gene expression is an early event in colorectal carcinogenesis.

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    Vibeke Andersen

    Full Text Available The ABCB1/MDR1 gene product ABCB1/P-glycoprotein is implicated in the development of colorectal cancer (CRC. NFKB1 encodes transcription factors regulating expression of a number of genes including ABCB1. We have previously found association between the ABCB1 C-rs3789243-T polymorphism and CRC risk and interactions between the ABCB1 C-rs3789243-T and C3435T polymorphisms and meat intake in relation to CRC risk (Andersen, BMC Cancer, 2009, 9, 407. ABCB1 and NFKB1 mRNA levels were assessed in intestinal tissue from 122 CRC cases, 101 adenoma cases (12 with severe dysplasia, 89 with mild-moderate dysplasia and from 18 healthy individuals, together with gene polymorphisms in ABCB1 and NFKB1. ABCB1 mRNA levels were highest in the healthy individuals and significantly lower in mild/moderate and severe dysplasia tissue (P<0.05 for both, morphologically normal tissues close to the tumour (P<0.05, morphologically normal tissue at a distance from the tumour (P<0.05 and CRC tissue (P<0.001. Furthermore, ABCB1 mRNA levels were lower in adenomas and carcinomas compared to morphologically normal tissue from the same individuals (P<0.01. The ABCB1 C-rs3789243-T and NFKB1 -94ins/del homozygous variant genotypes were associated with low ABCB1 mRNA levels in morphologically normal sigmoid tissue from adenoma cases (P<0.05 for both. NFKB1 mRNA levels were lower in both tumour and normal tissue from cancer patients (P<0.001 as compared to healthy individuals but we were unable to show association between NFKB1 -94ins/del genotype and NFKB1 mRNA levels. This study suggests that low ABCB1 mRNA levels are an early event in CRC development and that the two polymorphisms affect ABCB1 mRNA levels whereas low NFKB1 mRNA levels occur later in carcinogenesis. Low ABCB1 protein levels may promote colorectal carcinogenesis through increasing intracellular exposure to carcinogenic ABCB1 substrates.

  6. Tumor suppressor microRNA-27a in colorectal carcinogenesis and progression by targeting SGPP1 and Smad2.

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    Yonghua Bao

    Full Text Available The aberrant expression of microRNAs (miRNAs is associated with colorectal carcinogenesis, but the underlying mechanisms are not clear. This study showed that the miRNA-27a (miR-27a was significantly reduced in colorectal cancer tissues and colorectal cancer cell lines, and that the reduced miR-27a was associated with distant metastasis and colorectal cancer clinical pathological stages-miR-27a was lower at stages III/IV than that at stage II. Bioinformatic and systemic biological analysis predicted several targets of miR-27a, among them SGPP1 and Smad2 were significantly affected. SGPP1 and Smad2 at mRNA and protein levels were negatively correlated with miR-27a in human colorectal cancer tissues and cancer cell lines. Increased miR-27a significantly repressed SGPP1 and Smad2 at transcriptional and translational levels. Functional studies showed that increasing miR-27a inhibited colon cancer cell proliferation, promoted apoptosis and attenuated cell migration, which were also linked to downregulation of p-STAT3 and upregulation of cleaved caspase 3. In vivo, miR-27a inhibited colon cancer cell growth in tumor-bearing mice. Taken together, this study has revealed miR-27a as a tumor suppressor and has identified SGPP1 and Smad2 as novel targets of miR-27a, linking to STAT3 for regulating cancer cell proliferation, apoptosis and migration in colorectal cancer. Therefore, miR-27a could be a useful biomarker for monitoring colorectal cancer development and progression, and also could have a therapeutic potential by targeting SGPP1, Smad2 and STAT3 for colorectal cancer therapy.

  7. Comfrey (Symphytum officinale. L. and Experimental Hepatic Carcinogenesis: A Short-Term Carcinogenesis Model Study

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    Maria Fernanda Pereira Lavieri Gomes

    2010-01-01

    Full Text Available Comfrey or Symphytum officinale (L. (Boraginaceae is a very popular plant used for therapeutic purposes. Since the 1980s, its effects have been studied in long-term carcinogenesis studies, in which Comfrey extract is administered at high doses during several months and the neoplastic hepatic lesions are evaluated. However, the literature on this topic is very poor considering the studies performed under short-term carcinogenesis protocols, such as the ‘resistant hepatocyte model’ (RHM. In these studies, it is possible to observe easily the phenomena related to the early phases of tumor development, since pre-neoplastic lesions (PNLs rise in about 1–2 months of chemical induction. Herein, the effects of chronic oral treatment of rats with 10% Comfrey ethanolic extract were evaluated in a RHM. Wistar rats were sequentially treated with N-nitrosodiethylamine (ip and 2-acetilaminofluorene (po, and submitted to hepatectomy to induce carcinogenesis promotion. Macroscopic/microscopic quantitative analysis of PNL was performed. Non-parametric statistical tests (Mann–Whitney and χ2 were used, and the level of significance was set at P ≤ 0.05. Comfrey treatment reduced the number of pre-neoplastic macroscopic lesions up to 1 mm (P ≤ 0.05, the percentage of oval cells (P = 0.0001 and mitotic figures (P = 0.007, as well as the number of Proliferating Cell Nuclear Antigen (PCNA positive cells (P = 0.0001 and acidophilic pre-neoplastic nodules (P = 0.05. On the other hand, the percentage of cells presenting megalocytosis (P = 0.0001 and vacuolar degeneration (P = 0.0001 was increased. Scores of fibrosis, glycogen stores and the number of nucleolus organizing regions were not altered. The study indicated that oral treatment of rats with 10% Comfrey alcoholic extract reduced cell proliferation in this model.

  8. Epithelial markers of colorectal carcinogenesis in ulcerative colitis and primary sclerosing cholangitis

    Science.gov (United States)

    Wohl, Pavel; Hucl, Tomas; Drastich, Pavel; Kamenar, David; Spicak, Julius; Honsova, Eva; Sticova, Eva; Lodererova, Alena; Matous, Jan; Hill, Martin; Wohl, Petr; Kucera, Milos

    2013-01-01

    AIM: To evaluate the expression of epithelial markers of colorectal carcinogenesis in patients with long-term ulcerative colitis (UC) and primary sclerosing cholangitis (PSC) before and after transplantation. METHODS: Eight patients with UC and PSC prior to liver transplantation (PSC-UC), 22 patients with UC after liver transplantation for PSC (OLT), 9 patients with active ulcerative colitis without PSC (UCA), 7 patients with UC in remission (UCR) and 10 controls (N) underwent colonoscopy with multiple biopsies. Specimens were analysed histologically and semi-quantitatively immunohistochemically for p53, Bcl-2 and cyclooxygenase-2 (COX-2) markers. Statistical analysis was performed by Kruskal-Wallis and Fisher’s exact tests. RESULTS: PSC-UC had a statistically significantly higher expression of p53 in the nondysplastic mucosa as compared to OLT, UCA, UCR and N (P < 0.05). We also found a statistically significant positive correlation between the incidence of PSC and the expression of p53 (P < 0.001). UCA had a higher p53 expression as compared to UCR. OLT had a significantly lower expression of p53 as compared with PSC-UC (P < 0.001). Bcl-2 had a significant higher bcl-2 expression as compared with controls. No difference in COX-2 expression between PSC-UC, UCR and UCA was found. UCA had higher COX-2 expression as compared to UCR. We also found a statistically significant positive correlation between the expression of COX-2 and p53. Patients after liver transplantation for PSC had a statistically significantly lower expression of the p53 compared with PSC-UC (P < 0.001). PSC-UC had the same inflammatory endoscopic activity as OLT and UCR when evaluated with the Mayo score. CONCLUSION: Our study shows that the nondysplatic mucosa of UC patients with PSC is characterised by a higher expression of the tumour suppressor gene p53, suggesting a higher susceptibility of cancer. This p53 overexpression correlates with the presence of PSC whilst it is not present in

  9. Colorectal Cancer Carcinogenesis: a Multivariate Genetic Model in a Cohort of Romanian Population.

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    Procopciuc, Lucia M; Osian, Gelu; Iancu, Mihaela

    2017-04-01

    The molecular mechanism of carcinogenesis of sporadic colorectal cancer (CRC) involves genes with roles in folate metabolism, genes involved in metabolization of carcinogenic compounds from diet and tobacco smoke, and genes related to the DNA repair process. The aim of the study was to examine whether the MTHFRC677T, MTHFR- A1298C, TS-2rpt/3rpt, TS-1494del6bp, NAT2*5C-C481T, NAT2*5A-T341C, NAT2*6B-G590A, NAT2*7B-G857A, NAT2*18-A845C, GSTM1-null, XRCC1-Arg399Gln, XRCC3-Thr241Met, XPD-Lys751Gln genetic variations are associated with CRC prognosis, in the presence of environmental and demographic factors. We genotyped 150 patients diagnosed with sporadic CRC using PCR-RFLP and sequencing methods. The performance of the final model was quantified using Nagelkerke's coefficient, the Hosmer-Lemeshow test, C statistics, and Somers' (D) index, capable of describing the model's goodness-of-fit and discrimination. Multiple logistic regression analysis established a significant independent association of NAT2*18-A845C, MTHFR-C677T, XRCC3-Thr241Met, NAT2*7B-G857A, XPD-Lys751Gln, XRCC1-Arg399Gln and NAT2*6BG590A with an increased prevalence of sporadic CRC, regardless of the presence/absence of colonic tumors. After an adjustment for other polymorphisms and environmental risk factors, the risk to develop sporadic CRC was 2.25 (p = 0.011) and 2.31 (p = 0.01) in association with the NAT2*18-A845C and MTHFR-C677T genetic variants, respectively. The risk increased to 3.22 (p = 0.0005) and 3.69 (p = 0.0009) in association with the XRCC3Thr241Met and NAT2*7B-G857A polymorphisms. Also, patients carrying the XPD-Lys751Gln, XRCC1Arg399Gln, and NAT2*6B-G590A polymorphisms had a 4.16 (p methylation and procarcinogen transformation into carcinogenic compounds in sporadic CRC risk and, also, the influence of environmental risk factors such as diet, smoking, and alcohol consumption on this association.

  10. Experimental Hepatic Carcinogenesis: Oxidative Stress and Natural Antioxidants

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    Velid Unsal

    2017-08-01

    Full Text Available Hepatocellular carcinoma is one of the most common cancers in the world, and it is influenced by agents such as DEN, 2-AAF, phenobarbital, alcohol, aflatoxin B1 metabolite or hepatitis viruses (B and C. Oxidative stress is becoming recognized as a key factor in the progression of hepatocarcinogenesis. Reactive oxygen species can play a leading role in initiation and promotion of hepatic carcinogenesis. The metabolites of DEN Diethylnitrosamine (DEN mediate the binding of tumour promoters by covalently binding to the DNA with one or two oxidation-providing electrons. 2-AAF is the inducer of DEN, and it is involved in tumour formation in the bladder and liver. Reactive Oxygen species (ROS; carbohydrates, lipids, DNA and enzymes, such as affect all important structures. Additionally, an excessive amount of ROS is highly toxic to cells. Antioxidants are protects against ROS, toxic substances, carcinogens. This review focuses on the literature on studies of Hepatic Carcinogenesis, oxidative stress and antioxidant therapy.

  11. Experimental Gastric Carcinogenesis in Cebus apella Nonhuman Primates

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    Silva, Tanielly Cristina Raiol; Andrade Junior, Edilson Ferreira; Rezende, Alexandre Pingarilho; Carneiro Muniz, José Augusto Pereira; Lacreta Junior, Antonio Carlos Cunha; Assumpção, Paulo Pimentel; Calcagno, Danielle Queiroz; Demachki, Samia; Rabenhorst, Silvia Helena Barem; Smith, Marília de Arruda Cardoso; Burbano, Rommel Rodriguez

    2011-01-01

    The evolution of gastric carcinogenesis remains largely unknown. We established two gastric carcinogenesis models in New-World nonhuman primates. In the first model, ACP03 gastric cancer cell line was inoculated in 18 animals. In the second model, we treated 6 animals with N-methyl-nitrosourea (MNU). Animals with gastric cancer were also treated with Canova immunomodulator. Clinical, hematologic, and biochemical, including C-reactive protein, folic acid, and homocysteine, analyses were performed in this study. MYC expression and copy number was also evaluated. We observed that all animals inoculated with ACP03 developed gastric cancer on the 9th day though on the 14th day presented total tumor remission. In the second model, all animals developed pre-neoplastic lesions and five died of drug intoxication before the development of cancer. The last surviving MNU-treated animal developed intestinal-type gastric adenocarcinoma observed by endoscopy on the 940th day. The level of C-reactive protein level and homocysteine concentration increased while the level of folic acid decreased with the presence of tumors in ACP03-inoculated animals and MNU treatment. ACP03 inoculation also led to anemia and leukocytosis. The hematologic and biochemical results corroborate those observed in patients with gastric cancer, supporting that our in vivo models are potentially useful to study this neoplasia. In cell line inoculated animals, we detected MYC immunoreactivity, mRNA overexpression, and amplification, as previously observed in vitro. In MNU-treated animals, mRNA expression and MYC copy number increased during the sequential steps of intestinal-type gastric carcinogenesis and immunoreactivity was only observed in intestinal metaplasia and gastric cancer. Thus, MYC deregulation supports the gastric carcinogenesis process. Canova immunomodulator restored several hematologic measurements and therefore, can be applied during/after chemotherapy to increase the tolerability and

  12. Experimental gastric carcinogenesis in Cebus apella nonhuman primates.

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    Joana de Fátima Ferreira Borges da Costa

    Full Text Available The evolution of gastric carcinogenesis remains largely unknown. We established two gastric carcinogenesis models in New-World nonhuman primates. In the first model, ACP03 gastric cancer cell line was inoculated in 18 animals. In the second model, we treated 6 animals with N-methyl-nitrosourea (MNU. Animals with gastric cancer were also treated with Canova immunomodulator. Clinical, hematologic, and biochemical, including C-reactive protein, folic acid, and homocysteine, analyses were performed in this study. MYC expression and copy number was also evaluated. We observed that all animals inoculated with ACP03 developed gastric cancer on the 9(th day though on the 14(th day presented total tumor remission. In the second model, all animals developed pre-neoplastic lesions and five died of drug intoxication before the development of cancer. The last surviving MNU-treated animal developed intestinal-type gastric adenocarcinoma observed by endoscopy on the 940(th day. The level of C-reactive protein level and homocysteine concentration increased while the level of folic acid decreased with the presence of tumors in ACP03-inoculated animals and MNU treatment. ACP03 inoculation also led to anemia and leukocytosis. The hematologic and biochemical results corroborate those observed in patients with gastric cancer, supporting that our in vivo models are potentially useful to study this neoplasia. In cell line inoculated animals, we detected MYC immunoreactivity, mRNA overexpression, and amplification, as previously observed in vitro. In MNU-treated animals, mRNA expression and MYC copy number increased during the sequential steps of intestinal-type gastric carcinogenesis and immunoreactivity was only observed in intestinal metaplasia and gastric cancer. Thus, MYC deregulation supports the gastric carcinogenesis process. Canova immunomodulator restored several hematologic measurements and therefore, can be applied during/after chemotherapy to increase the

  13. Plant Foods versus Compounds in Carcinogenesis: Observational versus Experimental Human Studies

    NARCIS (Netherlands)

    Kampman, E.; Arts, I.C.W.; Hollman, P.C.H.

    2003-01-01

    The protective role of plant foods and its constituents in cancer prevention is under renewed debate since the results of recent observational studies on colorectal cancer as well as large-scale human experimental studies on colorectal adenoma recurrence are disappointing. However, most short-term

  14. Modulation of dietary fat-enhanced colorectal carcinogenesis in N-methyl-N'-nitro-N-nitrosoguanidine-treated rats by a vegetables-fruit mixture

    NARCIS (Netherlands)

    Rijnkels, J.M.; Hollanders, V.H.M.; Woutersen, R.A.; Koeman, J.H.; Alink, G.M.

    1997-01-01

    The modulation of a vegetables-fruit mixture on N-methyl-N'-nitro-N- nitrosoguanidine (MNNG)-induced colorectal carcinogenesis was studied in rats maintained on a low- or a high-fat diet. Far this purpose, 120 rats received a semisynthetic diet without (Groups A and C) or with a vegetables-fruit

  15. BRAF, KRAS and PIK3CA mutations in colorectal serrated polyps and cancer: Primary or secondary genetic events in colorectal carcinogenesis?

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    Schmitt Fernando

    2008-09-01

    Full Text Available Abstract Background BRAF, KRAS and PIK3CA mutations are frequently found in sporadic colorectal cancer (CRC. In contrast to KRAS and PIK3CA mutations, BRAF mutations are associated with tumours harbouring CpG Island methylation phenotype (CIMP, MLH1 methylation and microsatellite instability (MSI. We aimed at determine the frequency of KRAS, BRAF and PIK3CA mutations in the process of colorectal tumourigenesis using a series of colorectal polyps and carcinomas. In the series of polyps CIMP, MLH1 methylation and MSI were also studied. Methods Mutation analyses were performed by PCR/sequencing. Bisulfite treated DNA was used to study CIMP and MLH1 methylation. MSI was detected by pentaplex PCR and Genescan analysis of quasimonomorphic mononucleotide repeats. Chi Square test and Fisher's Exact test were used to perform association studies. Results KRAS, PIK3CA or BRAF occur in 71% of polyps and were mutually exclusive. KRAS mutations occur in 35% of polyps. PIK3CA was found in one of the polyps. V600E BRAF mutations occur in 29% of cases, all of them classified as serrated adenoma. CIMP phenotype occurred in 25% of the polyps and all were mutated for BRAF. MLH1 methylation was not detected and all the polyps were microsatellite stable. The comparison between the frequency of oncogenic mutations in polyps and CRC (MSI and MSS lead us to demonstrate that KRAS and PIK3CA are likely to precede both types of CRC. BRAF mutations are likely to precede MSI carcinomas since the frequency found in serrated polyps is similar to what is found in MSI CRC (P = 0.9112, but statistically different from what is found in microsatellite stable (MSS tumours (P = 0.0191. Conclusion Our results show that BRAF, KRAS and PIK3CA mutations occur prior to malignant transformation demonstrating that these oncogenic alterations are primary genetic events in colorectal carcinogenesis. Further, we show that BRAF mutations occur in association with CIMP phenotype in colorectal

  16. Interactive effects between dietary fat and a vegetables-fruit mixture on colorectal carcinogenesis

    NARCIS (Netherlands)

    Rijnkels, J.M.

    1998-01-01

    Several dietary compounds are associated with colorectal cancer risk. These include the amount of dietary fat, which is positively associated with colorectal cancer, and a variety of vegetables and fruit, which are suggested to possess anticarcinogenic potential. Because diet is complex and

  17. Quercetin, but Not Its Glycosidated Conjugate Rutin, Inhibits Azoxymethane-Induced Colorectal Carcinogenesis in F344 Rats

    NARCIS (Netherlands)

    Dihal, A.A.; Boer, de V.C.J.; Woude, van der H.; Tilburgs, C.; Bruintjes, J.P.; Alink, G.M.; Rietjens, I.M.C.M.; Woutersen, R.A.; Stierum, R.H.

    2006-01-01

    The effect of the flavonoid quercetin and its conjugate rutin was investigated on (biomarkers of) colorectal cancer (CRC). Male F344 rats (n = 42/group) were fed 0, 0.1, 1, or 10 g quercetin/kg diet or 40 g rutin/kg diet. Two wk after initial administration of experimental diets, rats were given 2

  18. Strawberry Phytochemicals Inhibit Azoxymethane/Dextran Sodium Sulfate-Induced Colorectal Carcinogenesis in Crj: CD-1 Mice

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    Ni Shi

    2015-03-01

    Full Text Available Human and experimental colon carcinogenesis are enhanced by a pro-inflammatory microenvironment. Pharmacologically driven chemopreventive agents and dietary variables are hypothesized to have future roles in the prevention of colon cancer by targeting these processes. The current study was designed to determine the ability of dietary lyophilized strawberries to inhibit inflammation-promoted colon carcinogenesis in a preclinical animal model. Mice were given a single i.p. injection of azoxymethane (10 mg kg−1 body weight. One week after injection, mice were administered 2% (w/v dextran sodium sulfate in drinking water for seven days and then an experimental diet containing chemically characterized lyophilized strawberries for the duration of the bioassay. Mice fed control diet, or experimental diet containing 2.5%, 5.0% or 10.0% strawberries displayed tumor incidence of 100%, 64%, 75% and 44%, respectively (p < 0.05. The mechanistic studies demonstrate that strawberries reduced expression of proinflammatory mediators, suppressed nitrosative stress and decreased phosphorylation of phosphatidylinositol 3-kinase, Akt, extracellular signal-regulated kinase and nuclear factor kappa B. In conclusion, strawberries target proinflammatory mediators and oncogenic signaling for the preventive efficacies against colon carcinogenesis in mice. This works supports future development of fully characterized and precisely controlled functional foods for testing in human clinical trials for this disease.

  19. Genotoxicity of Cytolethal Distending Toxin (CDT on isogenic human colorectal cell lines: potential promoting effects for colorectal carcinogenesis

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    Vanessa eGraillot

    2016-03-01

    Full Text Available The composition of the human microbiota influences tumorigenesis, notably in colorectal cancer (CRC. Pathogenic Escherichia coli possesses a variety of virulent factors, among them the Cytolethal Distending Toxin (CDT. CDT displays dual DNase and phosphatase activities and induces DNA double strand breaks, cell cycle arrest and apoptosis in a broad range of mammalian cells. As CDT could promote malignant transformation, we investigated the cellular outcomes induced by acute and chronic exposures to E. coli CDT in normal human colon epithelial cells (HCECs. Moreover, we conducted a comparative study between isogenic derivatives cell lines of the normal HCECs in order to mimic the mutation of three major genes found in CRC genetic models: APC, KRAS and TP53. Our results demonstrate that APC and p53 deficient cells showed impaired DNA damage response after CDT exposure, whereas HCECs expressing oncogenic KRASV12 were more resistant to CDT. Compared to normal HCECs, the precancerous derivatives exhibit hallmarks of malignant transformation after a chronic exposure to CDT. HCECs defective in APC and p53 showed enhanced anchorage independent growth and genetic instability, assessed by the micronucleus formation assay. In contrast, the ability to grow independently of anchorage was not impacted by CDT chronic exposure in KRASV12 HCECs, but micronucleus formation is dramatically increased. Thus CDT does not initiate CRC by itself, but may have promoting effects in premalignant HCECs, involving different mechanisms in function of the genetic alterations associated to CRC.

  20. Intestinal PTGS2 mRNA Levels, PTGS2 Gene Polymorphisms, and Colorectal Carcinogenesis

    DEFF Research Database (Denmark)

    Vogel, Lotte K.; Saebo, Mona; Hoyer, Helle

    2014-01-01

    Background & Aims: Inflammation is a major risk factor for development of colorectal cancer (CRC). Prostaglandin synthase cyclooxygenase-2 (COX-2) encoded by the PTGS2 gene is the rate limiting enzyme in prostaglandin synthesis and therefore plays a distinct role as regulator of inflammation....... Methods: PTGS2 mRNA levels were determined in intestinal tissues from 85 intestinal adenoma cases, 115 CRC cases, and 17 healthy controls. The functional PTGS2 polymorphisms A-1195G (rs689466), G-765C (rs20417), T8473C (rs5275) were assessed in 200 CRC cases, 991 adenoma cases and 399 controls from...

  1. Low ABCB1 gene expression is an early event in colorectal carcinogenesis

    DEFF Research Database (Denmark)

    Andersen, Vibeke; Vogel, Ulla Birgitte; Godiksen, Sine

    2013-01-01

    risk and interactions between the ABCB1 C-rs3789243-T and C3435T polymorphisms and meat intake in relation to CRC risk (Andersen, BMC Cancer, 2009, 9, 407). ABCB1 and NFKB1 mRNA levels were assessed in intestinal tissue from 122 CRC cases, 101 adenoma cases (12 with severe dysplasia, 89 with mild......The ABCB1/MDR1 gene product ABCB1/P-glycoprotein is implicated in the development of colorectal cancer (CRC). NFKB1 encodes transcription factors regulating expression of a number of genes including ABCB1. We have previously found association between the ABCB1 C-rs3789243-T polymorphism and CRC...

  2. Molecular evolution of colorectal cancer: from multistep carcinogenesis to the big bang.

    Science.gov (United States)

    Amaro, Adriana; Chiara, Silvana; Pfeffer, Ulrich

    2016-03-01

    Colorectal cancer is characterized by exquisite genomic instability either in the form of microsatellite instability or chromosomal instability. Microsatellite instability is the result of mutation of mismatch repair genes or their silencing through promoter methylation as a consequence of the CpG island methylator phenotype. The molecular causes of chromosomal instability are less well characterized. Genomic instability and field cancerization lead to a high degree of intratumoral heterogeneity and determine the formation of cancer stem cells and epithelial-mesenchymal transition mediated by the TGF-β and APC pathways. Recent analyses using integrated genomics reveal different phases of colorectal cancer evolution. An initial phase of genomic instability that yields many clones with different mutations (big bang) is followed by an important, previously not detected phase of cancer evolution that consists in the stabilization of several clones and a relatively flat outgrowth. The big bang model can best explain the coexistence of several stable clones and is compatible with the fact that the analysis of the bulk of the primary tumor yields prognostic information.

  3. The protective role of Lychnophora ericoides Mart. (Brazilian arnica) in 1,2-dimethylhydrazine-induced experimental colon carcinogenesis.

    Science.gov (United States)

    Fernandes, Cleverson Rodrigues; Turatti, Aline; Gouvea, Dayana Rubio; Gobbo-Neto, Leonardo; Diniz, Andrea; Ribeiro-Silva, Alfredo; Lopes, Norberto Peporine; Garcia, Sérgio Britto

    2011-01-01

    Aberrant crypt foci (ACF) and colon rectal mucosal epithelial cell proliferation have been shown to be increased in patients with colon cancer and have been largely used for early detection of factors that influence colorectal carcinogenesis in rats. Fifty male Wistar rats were randomly divided into 5 groups. The groups G1 to G4 were given 4 injections of the carcinogen 1,2-dimethylhydrazine (DMH). The G2 group received Lychnophora ericoides (LE) extracts for 6 wk. The groups G3 and G4 received LE for 4 wk and 2 wk, respectively, at the postinitiation and initiation phases of colonic carcinogenesis. The group G5 was the control. Forty-two days after the first injections of DMH for the neoplasic induction, we observed a statistically significant decrease in the number of aberrant crypt foci (ACF) and an attenuation of the increase in cell proliferation induced by DMH in all the LE-treated groups. Thus, we concluded that Lychnophora ericoides extracts were effective against the development of cancer. These data suggest that LE has a protective influence on the process of colon carcinogenesis, suppressing both the initiation and the promotion of colonic carcinogenesis.

  4. Time-serial Assessment of Drug Combination Interventions in a Mouse Model of Colorectal Carcinogenesis Using Optical Coherence Tomography

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    Susan LeGendre-McGhee

    2015-01-01

    Full Text Available Optical coherence tomography (OCT is a high-resolution, nondestructive imaging modality that enables time-serial assessment of adenoma development in the mouse model of colorectal cancer. In this study, OCT was utilized to evaluate the effectiveness of interventions with the experimental antitumor agent α-difluoromethylornithine (DFMO and a nonsteroidal anti-inflammatory drug sulindac during early [chemoprevention (CP] and late stages [chemotherapy (CT] of colon tumorigenesis. Biological endpoints for drug interventions included OCT-generated tumor number and tumor burden. Immunochistochemistry was used to evaluate biochemical endpoints [Ki-67, cleaved caspase-3, cyclooxygenase (COX-2, β-catenin]. K-Ras codon 12 mutations were studied with polymerase chain reaction-based technique. We demonstrated that OCT imaging significantly correlated with histological analysis of both tumor number and tumor burden for all experimental groups ( P < 0.0001, but allows more accurate and full characterization of tumor number and burden growth rate because of its time-serial, nondestructive nature. DFMO alone or in combination with sulindac suppressed both the tumor number and tumor burden growth rate in the CP setting because of DFMO-mediated decrease in cell proliferation (Ki-67, P < 0.001 and K-RAS mutations frequency ( P = 0.04. In the CT setting, sulindac alone and DFMO/sulindac combination were effective in reducing tumor number, but not tumor burden growth rate. A decrease in COX-2 staining in DFMO/sulindac CT groups (COX-2, P < 0.01 confirmed the treatment effect. Use of nondestructive OCT enabled repeated, quantitative evaluation of tumor number and burden, allowing changes in these parameters to be measured during CP and as a result of CT. In conclusion, OCT is a robust minimally invasive method for monitoring colorectal cancer disease and effectiveness of therapies in mouse models.

  5. Cancer Targeting Potential of 99mTc-Finasteride in Experimental Model of Prostate Carcinogenesis.

    Science.gov (United States)

    Jan, Gowsia; Passi, Neelima D; Dhawan, Devinder Kumar; Chadha, Vijayta Dani

    2017-03-01

    This study aimed to radiolabel finasteride, a novel 5α-reductase inhibitor, to evaluate its cancer targeting potential in experimental model of prostate carcinogenesis. Finasteride was effectively radiolabeled with 99mTc and showed >90% labeling efficiency. The radiopharmaceutical was found to be stable up to 6 hours in rat serum at 37°C. The blood kinetics of the 99mTc-finasteride followed a biphasic release pattern, whereby fast-release phase was observed at 15 seconds and a slow-release phase was observed after 30 minutes of administration. The plasma protein binding of the radio complex observed was 83.89%. For biodistribution studies, the rats were divided into two groups. Group I served as normal controls, while group II was subjected to carcinogen N-methyl-N-nitrosourea (MNU) and hormone testosterone propionate (T) for induction of prostate carcinogenesis, which was confirmed histopathologically. The biodistribution studies on control and carcinogen-treated rats revealed a significant percent-specific uptake in prostate, which was found to be increased significantly as a function of time. The most significant finding of the study was an increase in the percent-specific uptake in prostate of carcinogen-treated animals when compared to the percent-specific uptake in prostate of normal rats after 2 and 4 hours postinjection. The study concludes that 99mTc-finasteride possesses selectively toward prostate cancer tissue and can be explored further for its role in detection of prostate cancer.

  6. Absence of an inhibitory effect of a vegetables-fruit mixture on the initiation and promotion phases of azoxymethane-induced colorectal carcinogenesis in rats fed low- or high-fat diets

    NARCIS (Netherlands)

    Rijnkels, J.M.; Hollanders, V.M.H.; Woutersen, R.A.; Koeman, J.H.; Alink, G.M.

    1998-01-01

    The potential inhibitory effects of a vegetables-fruit mixture on the initiation and promotion phases of azoxymethane-induced colorectal carcinogenesis were examined in rats fed low- or high-fat diets. Rats were fed low-fat diets (20 energy percent, Diets A and B) or high-fat diets (40 energy

  7. Chemical carcinogenesis.

    Science.gov (United States)

    Oliveira, Paula A; Colaço, Aura; Chaves, Raquel; Guedes-Pinto, Henrique; De-La-Cruz P, Luis F; Lopes, Carlos

    2007-12-01

    The use of chemical compounds benefits society in a number of ways. Pesticides, for instance, enable foodstuffs to be produced in sufficient quantities to satisfy the needs of millions of people, a condition that has led to an increase in levels of life expectancy. Yet, at times, these benefits are offset by certain disadvantages, notably the toxic side effects of the chemical compounds used. Exposure to these compounds can have varying effects, ranging from instant death to a gradual process of chemical carcinogenesis. There are three stages involved in chemical carcinogenesis. These are defined as initiation, promotion and progression. Each of these stages is characterised by morphological and biochemical modifications and result from genetic and/or epigenetic alterations. These genetic modifications include: mutations in genes that control cell proliferation, cell death and DNA repair--i.e. mutations in proto-oncogenes and tumour suppressing genes. The epigenetic factors, also considered as being non-genetic in character, can also contribute to carcinogenesis via epigenetic mechanisms which silence gene expression. The control of responses to carcinogenesis through the application of several chemical, biochemical and biological techniques facilitates the identification of those basic mechanisms involved in neoplasic development. Experimental assays with laboratory animals, epidemiological studies and quick tests enable the identification of carcinogenic compounds, the dissection of many aspects of carcinogenesis, and the establishment of effective strategies to prevent the cancer which results from exposure to chemicals.

  8. Combined genotoxic effects of a polycyclic aromatic hydrocarbon (B(aP and an heterocyclic amine (PhIP in relation to colorectal carcinogenesis.

    Directory of Open Access Journals (Sweden)

    Emilien L Jamin

    Full Text Available Colorectal neoplasia is the third most common cancer worldwide. Environmental factors such as diet are known to be involved in the etiology of this cancer. Several epidemiological studies have suggested that specific neo-formed mutagenic compounds related to meat consumption are an underlying factor involved in the association between diet and colorectal cancer. Heterocyclic amines (HCAs and polycyclic aromatic hydrocarbons (PAHs are known mutagens and possible human carcinogens formed at the same time in meat during cooking processes. We studied the genotoxicity of the model PAH benzo(apyrene (B(aP and HCA 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP, alone or in mixture, using the mouse intestinal cell line Apc(Min/+, mimicking the early step of colorectal carcinogenesis, and control Apc(+/+ cells. The genotoxicity of B(aP and PhIP was investigated using both cell lines, through the quantification of B(aP and PhIP derived DNA adducts, as well as the use of a genotoxic assay based on histone H2AX phosphorylation quantification. Our results demonstrate that heterozygous Apc mutated cells are more effective to metabolize B(aP. We also established in different experiments that PhIP and B(aP were more genotoxic on Apc (Min/+ cells compared to Apc (+/+ . Moreover when tested in mixture, we observed a combined genotoxicity of B(aP and PhIP on the two cell lines, with an increase of PhIP derived DNA adducts in the presence of B(aP. Because of their genotoxic effects observed on heterozygous Apc mutated cells and their possible combined genotoxic effects, both B(aP and PhIP, taken together, could be implicated in the observed association between meat consumption and colorectal cancer.

  9. Raman Spectroscopy of Experimental Oral Carcinogenesis: Study on Sequential Cancer Progression in Hamster Buccal Pouch Model.

    Science.gov (United States)

    Kumar, Piyush; Bhattacharjee, Tanmoy; Ingle, Arvind; Maru, Girish; Krishna, C Murali

    2016-10-01

    Oral cancers suffer from poor 5-year survival rates, owing to late detection of the disease. Current diagnostic/screening tools need to be upgraded in view of disadvantages like invasiveness, tedious sample preparation, long output times, and interobserver variances. Raman spectroscopy has been shown to identify many disease conditions, including oral cancers, from healthy conditions. Further studies in exploring sequential changes in oral carcinogenesis are warranted. In this Raman spectroscopy study, sequential progression in experimental oral carcinogenesis in Hamster buccal pouch model was investigated using 3 approaches-ex vivo, in vivo sequential, and in vivo follow-up. In all these studies, spectral changes show lipid dominance in early stages while later stages and tumors showed increased protein to lipid ratio and nucleic acids. On similar lines, early weeks of 7,12-dimethylbenz(a)anthracene-treated and control groups showed higher overlap and low classification. The classification efficiency increased progressively, reached a plateau phase and subsequently increased up to 100% by 14 weeks. The misclassifications between treated and control spectra suggested some changes in controls as well, which was confirmed by a careful reexamination of histopathological slides. These findings suggests Raman spectroscopy may be able to identify microheterogeneity, which may often go unnoticed in conventional biochemistry wherein tissue extracts are employed, as well as in histopathology. In vivo findings, quite comparable to gold-standard supported ex vivo findings, give further proof of Raman spectroscopy being a promising label-free, noninvasive diagnostic adjunct for future clinical applications. © The Author(s) 2015.

  10. Life style-related diseases of the digestive system: colorectal cancer as a life style-related disease: from carcinogenesis to medical treatment.

    Science.gov (United States)

    Takahashi, Hirokazu; Yoneda, Kyoko; Tomimoto, Ayako; Endo, Hiroki; Fujisawa, Toshio; Iida, Hiroshi; Mawatari, Hironori; Nozaki, Yuichi; Ikeda, Tamon; Akiyama, Tomoyuki; Yoneda, Masato; Inamori, Masahiko; Abe, Yasunobu; Saito, Satoru; Nakajima, Atsushi; Nakagama, Hitoshi

    2007-10-01

    Life style-related diseases are associated with an increased risk of colorectal cancer (CRC). Recently, an association has been demonstrated between obesity and CRC. CRC has been associated with markers of insulin or glucose control, and insulin resistance might be the unifying mechanism by which several risk factors affect colorectal carcinogenesis. We evaluated the association between the number of aberrant crypt foci (ACF) and obesity, insulin resistance, hyperlipidemia, and other factors of life style-related disease. As a result, age, body mass index (BMI), waist circumference, and visceral fat obesity were significantly associated with the number of ACF. These results suggest that visceral fat obesity is an important target for CRC prevention. Peroxisome proliferator-activated receptor gamma (PPARgamma) is a member of the nuclear receptor superfamily and is highly expressed in CRC. PPARgamma ligand administration for 1 to 8 months significantly reduced the number of ACF in human subjects. PPARgamma ligand is a promising candidate as a chemopreventive agent. Further investigation is needed to elucidate these mechanisms.

  11. Nutrients, Foods, and Colorectal Cancer Prevention

    Science.gov (United States)

    Song, Mingyang; Garrett, Wendy S.; Chan, Andrew T.

    2015-01-01

    Diet has an important role in the development of colorectal cancer. In the past few decades, findings from extensive epidemiologic and experimental investigation have linked consumption of several foods and nutrients to the risk of colorectal neoplasia. Calcium, fiber, milk, and whole grain have been associated with a lower risk of colorectal cancer, and red meat and processed meat with an increased risk. There is substantial evidence for the potential chemopreventive effects of vitamin D, folate, fruits and vegetables. Nutrients and foods may also interact, as a dietary pattern, to influence colorectal cancer risk. Diet likely influences colorectal carcinogenesis through several interacting mechanisms. These include the direct effects on immune responsiveness and inflammation, and the indirect effects of over-nutrition and obesity—risk factors for colorectal cancer. Emerging evidence also implicates the gut microbiota as an important effector in the relationship between diet and cancer. Dietary modification therefore has the promise of reducing colorectal cancer incidence. PMID:25575572

  12. The anti-cancer effects of Tualang honey in modulating breast carcinogenesis: an experimental animal study.

    Science.gov (United States)

    Ahmed, Sarfraz; Othman, Nor Hayati

    2017-04-11

    Honey has been shown to have anti-cancer effects, but the mechanism behind these effects is not fully understood. We investigated the role of Malaysian jungle Tualang honey (TH) in modulating the hematological parameters, estrogen, estrogen receptors (ER1) and pro and anti-apoptotic proteins expression in induced breast cancer in rats. Fifty nulliparous female Sprague-Dawley rats were used and grouped as follows: Group 0 (healthy normal rats control), Group 1 (negative control; untreated rats), Groups 2, 3 and 4 received daily doses of 0.2, 1.0 and 2.0 g/kg body weight of TH, respectively. The rats in groups 1, 2, 3, 4 were induced with 80 mg/kg of 1-methyl-1-nitrosourea (MNU). TH treatment in groups 2, 3 and 4 was started one week prior to tumor induction and continued for 120 days. The TH-treated rats had tumors of different physical attributes compared to untreated negative control rats; the tumor progression (mean 75.3 days versus 51.5 days); the incidence (mean 76.6% versus 100%); the multiplicity (mean 2.5 versus 4 tumor masses per rat); the size of tumor mass (mean 0.41 cm versus 1.47 cm [p Honey alleviates breast carcinogenesis through modulation of hematologic, estrogenic and apoptotic activities in this experimental breast cancer animal model. Tualang Honey may be used as a natural 'cancer-alleviating' agent or as a supplement to chemotherapeutic agents.

  13. The RS4939827 polymorphism in the SMAD7 GENE and its association with Mediterranean diet in colorectal carcinogenesis.

    Science.gov (United States)

    Alonso-Molero, Jéssica; González-Donquiles, Carmen; Palazuelos, Camilo; Fernández-Villa, Tania; Ramos, Elena; Pollán, Marina; Aragonés, Nuria; Llorca, Javier; Henar Alonso, M; Tardón, Adonina; Amiano, Pilar; Moleon, José Juan Jiménez; Pérez, Rosana Peiró; Capelo, Rocío; Molina, Antonio J; Acebo, Inés Gómez; Guevara, Marcela; Gómez, Beatriz Pérez; Lope, Virginia; Huerta, José María; Castaño-Vinyals, Gemma; Kogevinas, Manolis; Moreno, Victor; Martín, Vicente

    2017-10-30

    The objective of our investigation is to study the relationship between the rs4939827 SNP in the SMAD7 gene, Mediterranean diet pattern and the risk of colorectal cancer. We examined 1087 cases of colorectal cancer and 2409 population controls with available DNA samples from the MCC-Spain study, 2008-2012. Descriptive statistical analyses, and multivariate logistic mixed models were performed. The potential synergistic effect of rs4939827 and the Mediterranean diet pattern was evaluated with logistic regression in different strata of of adherence to the Mediterranean diet and the genotype. High adherence to Mediterrenean diet was statistically significantly associated with colorectal cancer risk. A decreased risk for CRC cancer was observed for the CC compared to the TT genotype (OR = 0.65 and 95% CI = 0.51-0.81) of the rs4939827 SNP Also, we could show an association between the Mediterranean diet pattern (protective factor) and rs4939827. Although the decreased risk for the CC genotype was slightly more pronounced in subjects with high adherence to Mediterrenean diet, there was no statistically significant synergistic effect between genotype CC and adherence to the Mediterranean dietary pattern factors. The SMAD7 gene and specifically the allele C could be protective for colorectal cancer. An independent protective association was also observed between high adherence Mediterranean diet pattern and CRC risk. Findings form this study indicate that high adherence to Mediterranean diet pattern has a protective role for CRC cancer probably involving the Tumor Growth Factor- β pathway in this cancer.

  14. The Dual Role of Inflammation in Colon Carcinogenesis

    Directory of Open Access Journals (Sweden)

    Carmine Stolfi

    2012-09-01

    Full Text Available Chronic inflammation characterizing patients with inflammatory bowel disease (IBD represents a major risk factor for the development of colorectal cancer. Mechanisms underlying this neoplastic transformation are not fully understood though studies in experimental models of colon carcinogenesis suggest that inflammatory cell-derived cytokines either directly or indirectly stimulate the uncontrolled growth of cancer cells. Nevertheless, under specific inflammatory conditions, immune cells can boost an anti-tumor immune response with the down-stream effect of eliminating dysplastic and cancerous cells. This review outlines the beneficial and detrimental role of inflammation in colon carcinogenesis.

  15. Smad2/3 linker phosphorylation is a possible marker of cancer stem cells and correlates with carcinogenesis in a mouse model of colitis-associated colorectal cancer.

    Science.gov (United States)

    Suzuki, Ryo; Fukui, Toshiro; Kishimoto, Masanobu; Miyamoto, Sachi; Takahashi, Yu; Takeo, Masahiro; Mitsuyama, Toshiyuki; Sakaguchi, Yutaku; Uchida, Kazushige; Nishio, Akiyoshi; Okazaki, Kazuichi

    2015-07-01

    Epithelial cells affected by somatic mutations undergo transition from a tumour-suppressive to a carcinogenic Smad pathway during sporadic colorectal carcinogenesis, and the specific linker threonine phosphorylation of Smad2/3 in colon epithelial cells indicates stem-like cells. This study extends previous observations to a model of colitis-associated colorectal cancer. After Crl:CD-1 mice received an administration of azoxymethane [AOM], the mice were given dextran sodium sulfate [DSS] for 7 days. AOM/DSS-treated mice [AOM/DSS mice] were killed at 10 or 20 weeks. After macroscopic observations, a histopathological analysis was conducted. Immunohistochemical staining was performed using the avidin-biotin immunoperoxidase method [pSmad3C-Ser, pSmad3L-Ser, c-Myc] and immunofluorescent methods [Ki67, β-catenin, CDK4, cyclin D1, Sox9, pSmad2/3L-Thr]. The colons from AOM/DSS mice were shorter than those from control mice. The number of colon tumours at Week 20 was higher than at Week 10. The inflammation scores for AOM/DSS mice were greater than those for control mice. Immunostaining-positive cells (staining by Ki67, β-catenin [nuclear and cytoplasmic], cyclin D1, and Sox9) were diffusely distributed in colon tumours. The percentage of pSmad3L-Ser-positive cells in colon tumours was higher than in sites of pre-neoplastic colitis, and that in sites of pre-neoplastic colitis was higher than in control mice. pSmad2/3L-Thr-positive cells were sparsely detected around crypt bases in non-neoplastic colon epithelia and at the tops of tumours, and immunohistochemical co-localisation of pSmad2/3L-Thr with Ki67 was not observed. Immunohistochemical co-localisation of pSmad2/3L-Thr with β-catenin and CDK4 was observed. pSmad3L-Ser signalling is an early event in colitis-associated colorectal cancer, and pSmad2/3L-Thr immunostaining-positive cells might be cancer stem cells. Copyright © 2015 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University

  16. Experimental model of pulmonary carcinogenesis in Wistar rats Modelo experimental de carcinogênese pulmonar em ratos Wistar

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    Baldomero Antonio Kato da Silva

    2007-01-01

    Full Text Available PURPOSE: To elaborate an experimental model of pulmonary carcinogenesis in Wistar rats. METHODS: Male Rattus norvegicus albinus, Wistar lineage was carried through an intra-pulmonary instillation of the Benzo[a]pyrene (B[a]P dilution in alcohol 70%, a polycyclic aromatic hydrocarbon widely known by its power of tumoral induction. Three experimental groups had been formed with 08 animals each: Control Group (Alcohol 70%; B[a]P Group 10 mg/kg; e B[a]P Group 20mg/kg, submitted to euthanasia 08, 10, 12 and 14 weeks after the experimental procedure. The pulmonary sections had been colored by hematoxilin-eosin (HE and submitted to the morphometrical analysis to describe the tissue alterations. RESULTS: The presence of diffuse inflammatory alterations was observed in all groups, however, at the analysis of the pulmonary tissue of the experimental groups, it had been observed hyperplasic alterations (BALT hyperplasia, and in one of the animals of the experimental group 20mg/kg (12 weeks, it was noticed the presence of cellular epithelial tracheal pleomorphism, suggesting the adenocarcinoma formation in situ. CONCLUSION: The main secondary alterations to the intra-pulmonary instillation of B[a]P in Wistar rats were: cellular proliferation, inflammatory alterations of several degrees and nodular lymphoid hyperplasias. The association of an activator agent of the pulmonary metabolic reply is necessary to establish the ideal reply-dose to the development of the lung cancer.OBJETIVO: Elaborar um modelo experimental de carcinogênese pulmonar em ratos wistar. MÉTODOS: Rattus norvegicus albinus, linhagem Wistar foram submetidos a instilação intra-pulmonar da diluição em álcool 70% de Benzo[a]pireno (B[a]P, um hidrocarboneto aromático policíclico amplamente conhecido por seu poder de indução tumoral. Foram formados três grupos experimentais com 08 animais cada: Grupo Controle (álcool 70%; Grupo B[a]P 10 mg/kg; e Grupo B[a]P 20mg/kg, submetidos a

  17. Gavage of Fecal Samples From Patients With Colorectal Cancer Promotes Intestinal Carcinogenesis in Germ-Free and Conventional Mice.

    Science.gov (United States)

    Wong, Sunny H; Zhao, Liuyang; Zhang, Xiang; Nakatsu, Geicho; Han, Juqiang; Xu, Weiqi; Xiao, Xue; Kwong, Thomas N Y; Tsoi, Ho; Wu, William K K; Zeng, Benhua; Chan, Francis K L; Sung, Joseph J Y; Wei, Hong; Yu, Jun

    2017-12-01

    Altered gut microbiota is implicated in development of colorectal cancer (CRC). Some intestinal bacteria have been reported to potentiate intestinal carcinogenesis by producing genotoxins, altering the immune response and intestinal microenvironment, and activating oncogenic signaling pathways. We investigated whether stool from patients with CRC could directly induce colorectal carcinogenesis in mice. We obtained stored stool samples from participants in a metagenome study performed in Hong Kong. Conventional (male C57BL/6) mice were given azoxymethane to induce colon neoplasia after receiving a course of antibiotics in drinking water. Mice were gavaged twice weekly with stool from 5 patients with CRC or 5 healthy individuals (controls) for 5 weeks. Germ-free C57BL/6 mice were gavaged once with stool from 5 patients with CRC or 5 controls. We collected intestinal tissues from mice and performed histology, immunohistochemistry, expression microarray, quantitative polymerase chain reaction, immunoblot, and flow cytometry analyses. We performed 16S ribosomal RNA gene sequencing analysis of feces from mice. Significantly higher proportions of conventional mice fed with stool from individuals with CRC than control stool developed high-grade dysplasia (P < .05) and macroscopic polyps (P < .01). We observed a higher proportion of proliferating (Ki-67-positive) cells in colons of germ-free mice fed with stool from patients with CRC vs those fed with stool from controls (P < .05). Feces from germ-free and conventional mice fed with stool from patients with CRC vs controls contained different microbial compositions, with lower richness in mice fed with stool from patients with CRC. Intestines collected from conventional and germ-free mice fed with stool from patients with CRC had increased expression of cytokines that modulate inflammation, including C-X-C motif chemokine receptor 1, C-X-C motif chemokine receptor 2, interleukin 17A (IL17A), IL22, and IL23A. Intestines

  18. Lactobacillus rhamnosus ATCC 7469 exopolysaccharides synergizes with low level ionizing radiation to modulate signaling molecular targets in colorectal carcinogenesis in rats.

    Science.gov (United States)

    Zahran, Walid E; Elsonbaty, Sawsan M; Moawed, Fatma S M

    2017-08-01

    Combination therapy that targets cellular signaling pathway represents an alternative therapy for the treatment of colon cancer (CRC). The present study was therefore aimed to investigate the probable interaction of Lactobacillus rhamnosus ATCC 7469 exopolysaccharides (EPS) with low level ionizing γ radiation (γ-R) exposure against dimethylhydrazine (DMH)- induced colorectal carcinogenesis in rats. Colon cancer was induced with 20mg DMH/kg BW. Rats received daily by gastric gavage 100mg EPS/Kg BW concomitant with 1Gy γ-R over two months. Colonic oxidative and inflammatory stresses were assessed. The change in the expression of p-p38 MAPK, p-STAT3, β-catenin, NF-kB, COX-2 and iNOS was evaluated by western blotting and q-PCR. It was found that DMH treatment significantly induced colon oxidative injury accompanied by inflammatory disturbance along with increased protein expression of the targeted signaling factors p-p38 MAPK, p-STAT3 and β-catenin. The mRNA gene expression of NF-kB, COX-2 and iNOS was significantly higher in DMH-treated animals. It's worthy to note that colon tissues with DMH treatment showed significant dysplasia and anaplasia of the glandular mucosal lining epithelium with loses of goblet cells formation, pleomorphism in the cells and hyperchromachia in nuclei. Interestingly, EPS treatment with γ-R exposure showed statistically significant amelioration of the oxidative and inflammatory biomarkers with modulated signaling molecular factors accompanied by improved histological structure against DMH-induced CRC. In conclusion, our findings showed that Lactobacillus rhamnosus ATCC 7469 EPS with low level γ-R in synergistic interaction are efficacious control against CRC progression throughout the modulation of key signaling growth factors associated with inflammation via antioxidant mediated anti-inflammatory and anti-proliferative activities. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  19. Plant-derived compounds in experimental inflammatory bowel disease and colon carcinogenesis

    OpenAIRE

    Fasolino, Ines

    2013-01-01

    Abstract Background Inflammatory bowel disease (IBD) and colorectal cancer (CRC) are widespread intestinal diseases. The link between these two diseases is highlighted by the observation that patients with IBD are at increased risk for CRC. Plants have been traditionally used in folk medicine and are actually practiced in industrialized countries where their use is often integrated into conventional medicine. Most survey agree that digestive tract ailments cure/prevention, including IBD an...

  20. Nonsense-Mediated mRNA Decay Impacts MSI-Driven Carcinogenesis and Anti-Tumor Immunity in Colorectal Cancers

    Science.gov (United States)

    El-Bchiri, Jamila; Guilloux, Agathe; Dartigues, Peggy; Loire, Etienne; Mercier, Dominique; Buhard, Olivier; Sobhani, Iradj; de la Grange, Pierre; Auboeuf, Didier; Praz, Françoise; Fléjou, Jean-François; Duval, Alex

    2008-01-01

    Nonsense-mediated mRNA Decay (NMD) degrades mutant mRNAs containing premature termination codon (PTC-mRNAs). Here we evaluate the consequence of NMD activity in colorectal cancers (CRCs) showing microsatellite instability (MSI) whose progression is associated with the accumulation of PTC-mRNAs encoding immunogenic proteins due to frameshift mutations in coding repeat sequences. Inhibition of UPF1, one of the major NMD factors, was achieved by siRNA in the HCT116 MSI CRC cell line and the resulting changes in gene expression were studied using expression microarrays. The impact of NMD activity was also investigated in primary MSI CRCs by quantifying the expression of several mRNAs relative to their mutational status and to endogenous UPF1 and UPF2 expression. Host immunity developed against MSI cancer cells was appreciated by quantifying the number of CD3ε-positive tumor-infiltrating lymphocytes (TILs). UPF1 silencing led to the up-regulation of 1251 genes in HCT116, among which a proportion of them (i.e. 38%) significantly higher than expected by chance contained a coding microsatellite (P<2×10−16). In MSI primary CRCs, UPF1 was significantly over-expressed compared to normal adjacent mucosa (P<0.002). Our data provided evidence for differential decay of PTC-mRNAs compared to wild-type that was positively correlated to UPF1 endogenous expression level (P = 0.02). A negative effect of UPF1 and UPF2 expression on the host's anti-tumor response was observed (P<0.01). Overall, our results show that NMD deeply influences MSI-driven tumorigenesis at the molecular level and indicate a functional negative impact of this system on anti-tumor immunity whose intensity has been recurrently shown to be an independent factor of favorable outcome in CRCs. PMID:18612427

  1. Nonsense-mediated mRNA decay impacts MSI-driven carcinogenesis and anti-tumor immunity in colorectal cancers.

    Directory of Open Access Journals (Sweden)

    Jamila El-Bchiri

    Full Text Available Nonsense-mediated mRNA Decay (NMD degrades mutant mRNAs containing premature termination codon (PTC-mRNAs. Here we evaluate the consequence of NMD activity in colorectal cancers (CRCs showing microsatellite instability (MSI whose progression is associated with the accumulation of PTC-mRNAs encoding immunogenic proteins due to frameshift mutations in coding repeat sequences. Inhibition of UPF1, one of the major NMD factors, was achieved by siRNA in the HCT116 MSI CRC cell line and the resulting changes in gene expression were studied using expression microarrays. The impact of NMD activity was also investigated in primary MSI CRCs by quantifying the expression of several mRNAs relative to their mutational status and to endogenous UPF1 and UPF2 expression. Host immunity developed against MSI cancer cells was appreciated by quantifying the number of CD3epsilon-positive tumor-infiltrating lymphocytes (TILs. UPF1 silencing led to the up-regulation of 1251 genes in HCT116, among which a proportion of them (i.e. 38% significantly higher than expected by chance contained a coding microsatellite (P<2x10(-16. In MSI primary CRCs, UPF1 was significantly over-expressed compared to normal adjacent mucosa (P<0.002. Our data provided evidence for differential decay of PTC-mRNAs compared to wild-type that was positively correlated to UPF1 endogenous expression level (P = 0.02. A negative effect of UPF1 and UPF2 expression on the host's anti-tumor response was observed (P<0.01. Overall, our results show that NMD deeply influences MSI-driven tumorigenesis at the molecular level and indicate a functional negative impact of this system on anti-tumor immunity whose intensity has been recurrently shown to be an independent factor of favorable outcome in CRCs.

  2. Experimental Animal Models of Pancreatic Carcinogenesis for Prevention Studies and Their Relevance to Human Disease

    Energy Technology Data Exchange (ETDEWEB)

    Takahashi, Mami, E-mail: mtakahas@ncc.go.jp; Hori, Mika; Mutoh, Michihiro [Division of Cancer Development System, Carcinogenesis Research Group, National Cancer Center Research Institute, 1-1, Tsukiji 5-chome, Chuo-ku, Tokyo 104-0045 (Japan); Wakabayashi, Keiji [Graduate School of Nutritional and Environmental Sciences, University of Shizuoka, Yada 52-1, Suruga-ku, Shizuoka 422-8526 (Japan); Nakagama, Hitoshi [Division of Cancer Development System, Carcinogenesis Research Group, National Cancer Center Research Institute, 1-1, Tsukiji 5-chome, Chuo-ku, Tokyo 104-0045 (Japan)

    2011-02-09

    Pancreatic cancer is difficult to cure, so its prevention is very important. For this purpose, animal model studies are necessary to develop effective methods. Injection of N-nitrosobis(2-oxopropyl)amine (BOP) into Syrian golden hamsters is known to induce pancreatic ductal adenocarcinomas, the histology of which is similar to human tumors. Moreover, K-ras activation by point mutations and p16 inactivation by aberrant methylation of 5′ CpG islands or by homozygous deletions have been frequently observed in common in both the hamster and humans. Thus, this chemical carcinogenesis model has an advantage of histopathological and genetic similarity to human pancreatic cancer, and it is useful to study promotive and suppressive factors. Syrian golden hamsters are in a hyperlipidemic state even under normal dietary conditions, and a ligand of peroxizome proliferator-activated receptor gamma was found to improve the hyperlipidemia and suppress pancreatic carcinogenesis. Chronic inflammation is a known important risk factor, and selective inhibitors of inducible nitric oxide synthase and cyclooxygenase-2 also have protective effects against pancreatic cancer development. Anti-inflammatory and anti-hyperlipidemic agents can thus be considered candidate chemopreventive agents deserving more attention.

  3. Chemical carcinogenesis

    Directory of Open Access Journals (Sweden)

    Paula A. Oliveira

    2007-12-01

    Full Text Available The use of chemical compounds benefits society in a number of ways. Pesticides, for instance, enable foodstuffs to be produced in sufficient quantities to satisfy the needs of millions of people, a condition that has led to an increase in levels of life expectancy. Yet, at times, these benefits are offset by certain disadvantages, notably the toxic side effects of the chemical compounds used. Exposure to these compounds can have varying effects, ranging from instant death to a gradual process of chemical carcinogenesis. There are three stages involved in chemical carcinogenesis. These are defined as initiation, promotion and progression. Each of these stages is characterised by morphological and biochemical modifications and result from genetic and/or epigenetic alterations. These genetic modifications include: mutations in genes that control cell proliferation, cell death and DNA repair - i.e. mutations in proto-oncogenes and tumour suppressing genes. The epigenetic factors, also considered as being non-genetic in character, can also contribute to carcinogenesis via epigenetic mechanisms which silence gene expression. The control of responses to carcinogenesis through the application of several chemical, biochemical and biological techniques facilitates the identification of those basic mechanisms involved in neoplasic development. Experimental assays with laboratory animals, epidemiological studies and quick tests enable the identification of carcinogenic compounds, the dissection of many aspects of carcinogenesis, and the establishment of effective strategies to prevent the cancer which results from exposure to chemicals.A sociedade obtém numerosos benefícios da utilização de compostos químicos. A aplicação dos pesticidas, por exemplo, permitiu obter alimento em quantidade suficiente para satisfazer as necessidades alimentares de milhões de pessoas, condição relacionada com o aumento da esperança de vida. Os benefícios estão, por

  4. Apoptotic role of natural isothiocyanate from broccoli (Brassica oleracea italica) in experimental chemical lung carcinogenesis.

    Science.gov (United States)

    Kalpana Deepa Priya, D; Gayathri, R; Gunassekaran, G R; Murugan, S; Sakthisekaran, D

    2013-05-01

    Sulforaphane (SFN) [1-isothiocyanato-4-(methylsulfinyl)butane] is a naturally occurring isothiocyanate found in cruciferous vegetables such as broccoli [Brassica oleracea L. var. italica Plenck. (Brassicaceae)]. Since it is among the most potent bioactive components with antioxidant and antitumor properties, it has received intense attention in the recent years for its chemopreventive properties. The present work determined the rehabilitating role in alleviating the oxidative damage caused by benzo(a)pyrene [B(a)P] to biomolecules and the apoptotic cascade mediated by orally administered isothiocyanate-SFN (9 µmol/mouse/day) against B(a)P (100 mg/kg body weight, i.p.) induced pulmonary carcinogenesis in Swiss albino mice. Oxidative damage was assessed by measuring lipid peroxidation, 8-hydroxydeoxyguanosine, hydrogen peroxide (H2O2) production, glycoprotein components, protein carbonyl levels and DNA-protein crosslinks. DNA fragmentation by agarose gel electrophoresis and caspase-3 activity by ELISA proved apoptotic induction by SFN along with the protein expression of Bcl-2, Bax and Cyt c. SFN treatment was found to decrease the H2O2 production (p < 0.001) in cancer induced animals, proving its antioxidant potential. Apoptosis was induced by increasing the release of Cyt c (p < 0.001) from mitochondria, decreasing and increasing the expression of Bcl-2 (p < 0.01) and Bax (p < 0.001), respectively. Caspase-3 activity was also enhanced (p < 0.001) which leads to DNA fragmentation in SFN treated groups. Our results reflect the rehabilitating role of SFN in B(a)P induced lung carcinogenesis.

  5. Inhibition of Bladder Tumor Growth by Chitooligosaccharides in an Experimental Carcinogenesis Model

    Directory of Open Access Journals (Sweden)

    João C. Fernandes

    2012-11-01

    Full Text Available Urinary bladder cancer is one of the most common cancers worldwide, with the highest incidence in industrialized countries. Patients with cancer commonly use unconventional and complementary therapy including nutraceuticals. In this study we evaluated the efficacy of chitooligosaccharides (in orange juice in rat bladder cancer chemoprevention and as therapeutic agent, on a rat model of urinary bladder carcinogenesis induced with N-butyl-N-(4-hydroxybutyl nitrosamine. Results indicate that chitooligosaccharides may have a preventive effect on bladder cancer development and a curative effect upon established bladder tumors, dependent on the concentration ingested 500 mg/kg b.w., every three days, showed capacity to inhibit and prevent the proliferation of bladder cancer; however, this was associated with secondary effects such as hypercholesterolemia and hypertriglyceridemia. The use of lower doses (50 and 250 mg/kg b.w. showed only therapeutic effects. It is further suggested that this antitumor effect might be due to its expected anti-inflammatory action, as well as by mechanisms not directly dependent of COX-2 inhibition, such as cellular proliferation control and improvement in antioxidant profile.

  6. Evaluation of the chemopreventive response of naringenin-loaded nanoparticles in experimental oral carcinogenesis using laser-induced autofluorescence spectroscopy

    Science.gov (United States)

    Sulfikkarali, N. K.; Krishnakumar, N.

    2013-04-01

    The aim of the present study is to investigate the chemopreventive effects of prepared naringenin-loaded nanoparticles (NARNPs) relative to the efficacy of free naringenin (NAR) in modifying the carcinogenic process and to study the changes in the endogenous fluorophores during DMBA-induced hamster buccal pouch (HBP) carcinogenesis by laser-induced autofluorescence (LIAF) spectroscopy. LIAF emission spectra from the hamster buccal mucosa of the control and experimental groups of animals were recorded in the 350-700 nm spectral range on a miniature fiber optic spectrometer from different anatomical sites of each group, with excitation at 404 nm from a diode laser. Oral squamous cell carcinoma (OSCC) was developed in the buccal pouch of golden Syrian hamsters by painting with 0.5% DMBA in liquid paraffin three times a week for 14 weeks. DMBA-painted animals revealed morphological changes, hyperplasia, dysplasia and well-differentiated squamous cell carcinoma. LIAF emission spectra showed significant difference between the control and tumor tissues. The tumor tissues are characterized by an increase in the emission of porphyrins and a decrease in the emission of nicotinamide adenine dinucleotide hydrogenase (NADH) and flavin adenine nucleotide (FAD) when compared to the control tissues. Furthermore, oral administration of NAR and its nanoparticulates restored the status of endogenous fluorophores in the buccal mucosa of DMBA-painted animals. On a comparative basis, the treatment of nanoparticulate naringenin was found to be more effective than free naringenin in completely preventing the formation of squamous cell carcinoma and in improving the status of endogenous porphyrins to a normal range in DMBA-induced hamster buccal pouch carcinogenesis. The result of the present study further suggests that LIAF spectroscopy may be a very valuable tool for rapid and sensitive detection of endogenous fluorophore changes in response to chemopreventive agents.

  7. Influence of rofecoxib on experimental colonic carcinogenesis in rats Influencia del rofecoxib sobre la carcinogénesis cólica experimental en ratas

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    J. F. Noguera Aguilar

    2004-10-01

    Full Text Available Aim: to investigate the effect of a selective cyclooxigenase-2 (COX-2 inhibitor, rofecoxib, in the prevalence of experimental colon tumors in rats. Experimental design: experimental study with 35 male Sprague-Dawley rats, divided into four groups: a control group without experimental manipulation (n = 5; b pharmacological carcinogenesis with 1-2 dimethylhydrazine dihydrocloride (n = 10; c pharmacological carcinogenesis and addition of acetylsalicylic acid (AAS (n = 10; and d carcinogenesis and addition of rofecoxib (n = 10. Carcinogenesis was induced with 1-2 dimethylhydrazine at a weekly dose of 25 mg/kg for 18 weeks. Colon tumors were isolated at 20 weeks. Antiinflammatory agents were given at a dose of AAS 30 mg/kg and rofecoxib at 3 mg/kg. Results: the percentage of colonic tumors was significantly reduced in the rofecoxib group. This result was found for all tumors and for the malignant lesions, adenocarcinomas. Conclusions: rofecoxib, a selective COX-2 inhibitor, reduced the percentage of drug-induced neoplastic glandular tissue in rats.Objetivo: investigar el efecto de un inhibidor selectivo de la ciclooxigenasa-2, rofecoxib, en la incidencia de tumores cólicos a nivel experimental. Diseño experimental: estudio experimental con 35 ratas Sprague-Dawley macho, asignadas aleatoriamente a uno de los cuatro grupos: a control (n=5, sin manipulación experimental; b carcinogénesis farmacológica (n=10; c carcinogénesis farmacológica y ácido acetilsalicílico (n=10, con administración de este fármaco al tiempo de la carcinogénesis farmacológica; y d carcinogénesis farmacológica y rofecoxib (n=10 con administración de este fármaco junto a la carcinogénesis farmacológica. La inducción carcinogénica se realizó con 1-2 dimetilhidrazina dihidrocloruro a dosis semanal de 25 mg/kg de peso durante 18 semanas. Se analizaron los tumores cólicos inducidos en la semana 20. Los antiinflamatorios se administraron por vía oral a razón de

  8. The potential effect of biological sealants on colorectal anastomosis healing in experimental research involving severe diabetes.

    Science.gov (United States)

    Stergios, K; Kontzoglou, K; Pergialiotis, V; Korou, L M; Frountzas, M; Lalude, O; Nikiteas, N; Perrea, D N

    2017-03-01

    Colorectal anastomoses continuous to pose a significant challenge in current surgical practice. Anastomotic leakage remains one of the most frequent and dramatic complications of colorectal surgery, even in centres of high specialisation. Diabetes is a well-established independent factor which results in higher anastomotic leakage rates. Fibrin sealants have been applied in experimental and clinical studies for the prevention of anastomotic dehiscence. However, little is known regarding their impact on diabetic patients. Several fibrin sealants have been proposed as adjunct to standard surgical techniques to prevent leakage from colonic anastomoses following the reversal of temporary colostomies, approved for general haemostasis. This review summarises current advances in colorectal anastomoses and provides evidence that may strengthen the need for tissue sealants in colorectal anastomoses of diabetic patients. We searched Medline (1966-2016) and Scopus (2004-2016) for current evidence in the field. To date, there is no evidence to support the use of fibrin sealants as an adjunct in diabetic patients who undergo colorectal surgery. Experimental animal models with extreme diabetes could be of significant use in the present field and further research is needed prior to application of fibrin sealants in a clinical setting.

  9. Epidemiological and Experimental Studies: The Role of Metformin on Colorectal Cancer

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    Ratih D. Yudhani

    2016-12-01

    Full Text Available GLOBOCAN data in 2012 showed colorectal cancer was the third leading cancer worldwide. In Indonesia, based on WHO data in 2014, colorectal cancer was the second common cancer ini men and third cancer in women. Epidemiological studies showed that diabetes mellitus have a correlation with the incidence of cancer and increase colorectal cancer risk by 30%. Some of epidemiological study showed that metformin therapy in diabetes patient reduce the risk of cancer incidence. It supported by experimental study which showed that metformin inhibit the growth and proliferation of cancer cells by influence the AMPK/mTOR pathway as a main role. The method was literature review based on publication at Pubmed, Scopus, and Google Scholar with keywords “metformin, colorectal cancer”, “metformin, colon cancer”, without index factor limitation in free journal and paid journal. The aim of this review is to give a new insight of metformin activity as anti-cancer and its potential for both preventif and adjuvant cancer therapy, especially for colorectal cancer.

  10. Wnt-signalling pathways and microRNAs network in carcinogenesis: experimental and bioinformatics approaches.

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    Onyido, Emenike K; Sweeney, Eloise; Nateri, Abdolrahman Shams

    2016-09-02

    Over the past few years, microRNAs (miRNAs) have not only emerged as integral regulators of gene expression at the post-transcriptional level but also respond to signalling molecules to affect cell function(s). miRNAs crosstalk with a variety of the key cellular signalling networks such as Wnt, transforming growth factor-β and Notch, control stem cell activity in maintaining tissue homeostasis, while if dysregulated contributes to the initiation and progression of cancer. Herein, we overview the molecular mechanism(s) underlying the crosstalk between Wnt-signalling components (canonical and non-canonical) and miRNAs, as well as changes in the miRNA/Wnt-signalling components observed in the different forms of cancer. Furthermore, the fundamental understanding of miRNA-mediated regulation of Wnt-signalling pathway and vice versa has been significantly improved by high-throughput genomics and bioinformatics technologies. Whilst, these approaches have identified a number of specific miRNA(s) that function as oncogenes or tumour suppressors, additional analyses will be necessary to fully unravel the links among conserved cellular signalling pathways and miRNAs and their potential associated components in cancer, thereby creating therapeutic avenues against tumours. Hence, we also discuss the current challenges associated with Wnt-signalling/miRNAs complex and the analysis using the biomedical experimental and bioinformatics approaches.

  11. Effect of green tea catechins on breast carcinogenesis: a systematic review of in-vitro and in-vivo experimental studies.

    Science.gov (United States)

    Yiannakopoulou, Eugenia Ch

    2014-03-01

    Catechins (flavan-3-oils) are the main flavonoids present in green tea. The potential cancer chemopreventive and therapeutic properties of green tea catechins have been the focus of research efforts in the last two decades. This systematic review aims to generate in vitro and in vivo data on the effect of green tea catechins on breast carcinogenesis. Electronic databases were searched with the appropriate search terms. Existing evidence suggests that green tea catechins modulate breast cell carcinogenesis. The effect of green tea catechins on breast cell carcinogenesis has been investigated in different experimental models and under different experimental conditions, that is, carcinogen investigated, green tea catechin dosage regimen, treatment with green tea extract versus pure synthetic EGCG, and time point of treatment with green tea catechins in relation to the exposure to the carcinogen. Although the effect of green tea catechins was not always statistically significant, the protective effect of green tea catechins was demonstrated in all the trials, suggesting that treatment with green tea catechins should be further investigated in the clinical setting of chemoprevention of high-risk women. However, it should be emphasized that the reported actions of green tea catechins are observed in high concentrations that are difficult to achieve in the clinical setting. This drawback could be overcome by designing green tea catechins with better bioavailability and/or by cotreatment combining breast cancer endocrine treatment with green tea catechins.

  12. Nutrients, foods, and colorectal cancer prevention.

    Science.gov (United States)

    Song, Mingyang; Garrett, Wendy S; Chan, Andrew T

    2015-05-01

    Diet has an important role in the development of colorectal cancer. In the past few decades, findings from extensive epidemiologic and experimental investigations have linked consumption of several foods and nutrients to the risk of colorectal neoplasia. Calcium, fiber, milk, and whole grains have been associated with a lower risk of colorectal cancer, and red meat and processed meat have been associated with an increased risk. There is substantial evidence for the potential chemopreventive effects of vitamin D, folate, fruits, and vegetables. Nutrients and foods also may interact, as a dietary pattern, to influence colorectal cancer risk. Diet likely influences colorectal carcinogenesis through several interacting mechanisms. These include the direct effects on immune responsiveness and inflammation, and the indirect effects of overnutrition and obesity-risk factors for colorectal cancer. Emerging evidence also implicates the gut microbiota as an important effector in the relationship between diet and cancer. Dietary modification therefore has the promise of reducing colorectal cancer incidence. Copyright © 2015 AGA Institute. Published by Elsevier Inc. All rights reserved.

  13. Molecular detection, quantification, and isolation of Streptococcus gallolyticus bacteria colonizing colorectal tumors: inflammation-driven potential of carcinogenesis via IL-1, COX-2, and IL-8

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    Abdulamir Ahmed S

    2010-09-01

    Full Text Available Abstract Background Colorectal cancer (CRC has long been associated with bacteremia and/or endocarditis by Streptococcus gallolyticus member bacteria (SGMB but the direct colonization of SGMB along with its molecular carcinogenic role, if any, has not been investigated. We assessed the colonization of SGMB in CRC patients with history of bacteremia (CRC-w/bac and without history of bacteremia (CRC-wo/bac by isolating SGMB from feces, mucosal surfaces of colorectum, and colorectal tissues and detecting SGMB DNA, via PCR and in situ hybridization (ISH assays targeting SodA gene in colorectal tissues. Moreover, mRNA of IL1, IL-8, COX-2, IFN-γ, c-Myc, and Bcl-2 in colorectal tissues of studied groups was assessed via ISH and RT-PCR. Results SGMB were found to be remarkably isolated in tumorous (TU and non-tumorous (NTU tissues of CRC-w/bac, 20.5% and 17.3%, and CRC-wo/bac, 12.8% and 11.5%, respectively while only 2% of control tissues revealed SGMB (P 10 CN/g respectively, showed higher colonization in TU than in NTU and in CRC-w/bac than in CRC-wo/bac (P Conclusions The current study indicated that colorectal cancer is remarkably associated with SGMB; moreover, molecular detection of SGMB in CRC was superior to link SGMB with CRC tumors highlighting a possible direct and active role of SGMB in CRC development through most probably inflammation-based sequel of tumor development or propagation via, but not limited to, IL-1, COX-2, and IL-8.

  14. Recent advances in metal carcinogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Sunderman, F.W. Jr.

    Recent advances in metal carcinogenesis are comprehensively reviewed, including (a) epidemiological and clinical aspects, (b) carcinogenesis bioassays, (c) bacterial mutagenesis, (d) mammalian cell mutagenesis, (e) chromosomal damage, (f) mammalian cell transformation, (g) microsomal metabolism, (h) DNA strandbreaks and crosslinks, (i) DNA polymerase infidelity, (j) RNA strand initiation, and (k) helical transition of B-DNA to Z-DNA. Based upon these observations, several hypotheses are proposed for the molecular pathogenesis of carcinogenesis by metal compounds. These hypotheses are amenable to experimental test by existing techniques of molecular biology.

  15. Regulation of biokinetics of (65)Zn by curcumin and zinc in experimentally induced colon carcinogenesis in rats.

    Science.gov (United States)

    Jain, Kinnri; Dhawan, Devinder K

    2014-10-01

    This study was conducted to investigate the role of curcumin and zinc on the biokinetics and biodistribution of (65)Zn during colon carcinogenesis. Male wistar rats were divided into five groups, namely normal control, 1,2-dimethylhydrazine (DMH) treated, DMH + curcumin treated, DMH + zinc treated, and DMH + curcumin + zinc treated. Weekly subcutaneous injections of DMH (30 mg/kg body weight) for 16 weeks initiated colon carcinogenesis. Curcumin (100 mg/kg body weight orally) and ZnSO4 (227 mg/L in drinking water) were supplemented for 16 weeks. This study revealed a significant depression in the fast (Tb1) and slow component (Tb2) of biological half-life of (65)Zn in the whole body of DMH-treated rats, whereas liver showed a significant elevation in these components. Further, DMH treatment showed a significant increase in the uptake values of (65)Zn in colon, small intestine, and kidneys. Subcellular distribution depicted a significant increase in (65)Zn uptake values in mitochondrial, microsomal, and postmicrosomal fractions of colon. However, curcumin and zinc supplementation when given separately or in combination reversed the trends and restored the uptake values close to normal range. Our study concludes that curcumin and zinc supplementation during colon carcinogenesis shall prove to be efficacious in regulating the altered zinc metabolism.

  16. Modelo de carcinogênese gástrica utilizando piloroplastia de Finney: estudo experimental em ratos Gastric carcinogenesis model using Finney pyloroplasty: experimental study in rats

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    Eliane de Marco Ferreira Kaminski

    2011-12-01

    estudados. CONCLUSÃO: 1 A piloroplastia à Finney é modelo experimental adequado de carcinogênese gástrica; 2 ela induziu refluxo duodenogástrico; 3 o refluxo duodenogástrico atuou como carcinógeno para o estômago; 4 não houve relação entre o pH gástrico e o desenvolvimento de carcinoma; 5 o nitrito de sódio não atuou como carcinógeno para o estômago dos ratos.BACKGROUND: The duodenogastric reflux has been implicated as a potential carcinogen for the stomach and esophagus and is one of the factors that may explain the development of gastric stump cancer. Experimental models of carcinogenesis in the stomach stump or in the duodenogastric anastomosis are well defined. AIM: To develop an experimental model of gastric carcinogenesis through the Finney pyloroplasty, evaluate the influence of ingestion of sodium nitrite in this model, analyze the concentrations of bile acids and the pH of the stomach. METHODS: A hundred and ten Wistar rats were operated and divided into four groups: Group I (15 rats underwent laparotomy (Sham group; Group II (15 rats underwent laparotomy (Sham and ingestion of sodium nitrite in drinking water; Group III (40 rats submitted to the Finney pyloroplasty and Group IV (40 rats submitted to the Finney pyloroplasty and ingestion of sodium nitrite in drinking water. After 50 weeks of surgery, the rats were sacrificed and samples collected for analysis of gastric pH, dosing of bile acids and histological analysis. RESULTS: The immediate postoperative mortality was 9%, and during the experiment, 10 rats died. The control group (I did not show gastric lesions; the control group with sodium nitrite (II developed papillomas in the pre-stomach in 16.6%; the operated groups with pyloroplasty had adenomas in 10.3% in Group III and 14.2 % in Group IV, and adenocarcinoma in 55.1% in group III and 14.2% in Group IV. The implementation of glands into the submucosa and muscle in the area of anastomosis (mucosa deployment was not sufficient criterion for

  17. In vivo measurement of the shape of the tissue-refractive-index correlation function and its application to detection of colorectal field carcinogenesis.

    Science.gov (United States)

    Gomes, Andrew J; Ruderman, Sarah; DelaCruz, Mart; Wali, Ramesh K; Roy, Hemant K; Backman, Vadim

    2012-04-01

    Polarization-gated spectroscopy is an established method to depth-selectively interrogate the structural properties of biological tissue. We employ this method in vivo in the azoxymethane (AOM)-treated rat model to monitor the morphological changes that occur in the field of a tumor during early carcinogenesis. The results demonstrate a statistically significant change in the shape of the refractive-index correlation function for AOM-treated rats versus saline-treated controls. Since refractive index is linearly proportional to mass density, these refractive-index changes can be directly linked to alterations in the spatial distribution patterns of macromolecular density. Furthermore, we found that alterations in the shape of the refractive-index correlation function shape were an indicator of both present and future risk of tumor development. These results suggest that noninvasive measurement of the shape of the refractive-index correlation function could be a promising marker of early cancer development.

  18. Dietary folate and APC mutations in sporadic colorectal cancer

    NARCIS (Netherlands)

    Vogel, S. de; Engeland, M. van; Lüchtenborg, M.; Bruïne, A.P. de; Roemen, G.M.J.M.; Lentjes, M.H.F.M.; Goldbohm, R.A.; Brandt, P.A. van den; Goeij, A.F.P.M. de; Weijenberg, M.P.

    2006-01-01

    Folate deficiency has been associated with colorectal cancer risk and may be involved in colorectal carcinogenesis through increased chromosome instability, gene mutations, and aberrant DNA methylation. Within the Netherlands Cohort Study on diet and cancer, we investigated the associations between

  19. Helicobacter pylori and colorectal neoplasia: Is there a causal link?

    Science.gov (United States)

    Papastergiou, Vasilios; Karatapanis, Stylianos; Georgopoulos, Sotirios D

    2016-01-01

    Ever since Helicobacter pylori (H. pylori) was recognized as an infectious cause of gastric cancer, there has been increasing interest in examining its potential role in colorectal carcinogenesis. Data from case-control and cross-sectional studies, mostly relying on hospital-based samples, and several meta-analyses have shown a positive statistical relationship between H. pylori infection and colorectal neoplasia. However, the possibility exists that the results have been influenced by bias, including the improper selection of patients and disparities with respect to potential confounders. While the evidence falls short of a definitive causal link, it appears that infection with H. pylori/H. pylori-related gastritis is associated with an increased, although modest, risk of colorectal adenoma and cancer. The pathogenic mechanisms responsible for this association remain uncertain. H. pylori has been detected in colorectal malignant tissues; however, the possibility that H. pylori is a direct activator of colonic carcinogenesis remains purely hypothetical. On the other hand, experimental data have indicated a series of potential oncogenic interactions between these bacteria and colorectal mucosa, including induction and perpetuation of inflammatory responses, alteration of gut microflora and release of toxins and/or hormonal mediators, such as gastrin, which may contribute to tumor formation. PMID:26811614

  20. Naringin accelerates the regression of pre-neoplastic lesions and the colorectal structural reorganization in a murine model of chemical carcinogenesis.

    Science.gov (United States)

    Sequetto, Priscila L; Oliveira, Tânia T; Maldonado, Izabel R S C; Augusto, Luís Eugênio F; Mello, Vanessa J; Pizziolo, Virginia R; Almeida, Márcia R; Silva, Marcelo E; Novaes, Rômulo D

    2014-02-01

    The aim of this study was to investigate the effect of Naringin on pre-neoplastic colorectal lesions induced by chemical carcinogen in rats. Female Wistar rats weighing 130.8±27.1 g received weekly one subcutaneous injection of 1,2-dimethylhydrazine (DMH, 20 mg/kg) for 10 weeks. The animals were divided into 5 groups with 6 animals in each group. Group 1: 0.9% saline; Group 2: DMH+0.9% saline; Group 3: DMH+Naringin (10 mg/kg); Group 4: DMH+Naringin (100 mg/kg); Group 5: DMH+Naringin (200 mg/kg). G2 and G3 showed a significant increase in ACF number, AgNOR/nucleus and mitosis compared to G1. G4 and G5 presented a significant reduction in these parameters compared to G2. The number of cells producing acidic and neutral mucins, red blood cells and the level of antioxidant minerals, such as copper, magnesium, selenium and zinc, were significantly reduced in G2 and G3, but similar in G4 and G5 compared to G1. Naringin, especially at 200 mg/kg, was effective in reducing the number of pre-neoplastic lesions in rats exposed to DMH. Some of these effects may be due to reduction in cellular proliferation and tissue levels of iron together with the recovery of antioxidant mineral levels induced by this flavonoid. Copyright © 2013 Elsevier Ltd. All rights reserved.

  1. Diet, aberrant crypt foci and colorectal cancer.

    Science.gov (United States)

    Bruce, W R; Archer, M C; Corpet, D E; Medline, A; Minkin, S; Stamp, D; Yin, Y; Zhang, X M

    1993-11-01

    We have used the aberrant crypt focus (ACF) assay to test and develop hypotheses linking diet and colon cancer. The hypotheses were suggested by epidemiological studies that identified possible dietary factors associated with colorectal cancer risk. The ACF assay was used to quantitate the effect of the dietary factors on the initiation and growth of these putative precursors of colon cancers in experimental animals. Using this approach we have developed 3 new hypotheses for the role of diet in colorectal cancer. These are (1) a risk associated with 5-hydroxymethyl-2-furaldehyde in caramelized sugar, (2) a risk associated with some factor in thermolyzed casein, and (3) a risk associated with single nutrient boluses of sucrose and fructose. The importance of these hypotheses has still to be tested in long term carcinogenesis experiments, in analytic epidemiology studies and then, perhaps, in intervention trials.

  2. Induction of experimental mammary carcinogenesis in rats with 7,12-dimethylbenz(aanthracene Indução da carcinogênese mamária experimental em ratas com 7,12-dimetilbenz(aantraceno

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    Alfredo Carlos S. D. Barros

    2004-01-01

    Full Text Available PURPOSE: To test an experimental model of chemical mammary carcinogenesis induction in rats. METHODS: Twenty young virgin Sprague-Dawley female rats, aged 47 days, received 20 mg of 7,12-dimethylbenz(aanthracene (DMBA intragastrically by gavage. Afterwards, at 8 and 13 weeks, their mammary glands were examined. At the end of the experiment, the animals were sacrificed, and the mammary tumors were measured and weighed. Tumor fragments were analyzed using light microscopy. RESULTS: Eight weeks after DMBA injection, 16 rats presented at least 1 breast tumor (80%. After 13 weeks, all of them (100% developed breast carcinomas that were confirmed by histopathological analysis. CONCLUSION: This experimental animal model of chemical mammary induced carcinogenesis is feasible and can be used in further experiments on the role of tumorigenic biomodulator substances.OBJETIVO: Testar um modelo experimental de indução química de carcinogênese mamária em ratas. MATERIAL E MÉTODOS: Com 47 dias de vida, 20 ratas Sprague-Dawley, jovens e virgens, receberam por gavagem intragástrica 20 mg de 7,12-dimetilbenz(aantraceno (DMBA. Oito e 13 semanas depois da injeção de droga as mamas das ratas foram examinadas. Ao final os animais foram sacrificados e fragmentos dos tumores foram estudados ao microscópio. RESULTADO: Oito semanas depois da injeção de DMBA 16 ratas apresentavam tumor nas mamas (80%. Com 13 semanas todas desenvolveram carcinomas de mama (100%, que foram confirmados por análise histopatológica. CONCLUSÃO: Este modelo experimental de indução química de carcinogênese mamária é factível e pode ser empregado em futuras pesquisas para avaliar o papel de substâncias biomoduladoras da tumorigênese.

  3. Mismatch repair defects in human carcinogenesis.

    Science.gov (United States)

    Eshleman, J R; Markowitz, S D

    1996-01-01

    Mismatch repair defects are carcinogenic. This conclusion comes some 80 years after the original description of a type of familial colorectal cancer in which mismatch repair defects are involved, and from decades of dedicated basic science research into fundamental mechanisms cells use to repair their DNA. Mismatch repair (MMR) was described first in bacteria, later in yeast and finally in higher eukaryotes. In bacteria, one of its roles is the rapid repair of replicative errors thereby providing the genome with a 100-1000-fold level of protection against mutation. It also guards the genome by preventing recombination between non-homologous regions of DNA. The information gained from bacteria suddenly became relevant to human neoplasia in 1993 when the RER phenotype of microsatellite instability was discovered in human cancers and was rapidly shown to be due to defects in mismatch repair. Evidence supporting the role of MMR defects in carcinogenesis comes from a variety of independent sources including: (i) theoretical considerations of the requirement for a mutator phenotype as a step in multistage carcinogenesis; (ii) discovering that MMR defects cause a 'mutator phenotype' destabilizing endogenous expressed genes including those integral to carcinogenesis; (iii) finding MMR defects in the germline of HNPCC kindred members; (iv) finding that such defects behave as classic tumor suppressor genes in both familial and sporadic colorectal cancers; (v) discovering that MMR 'knockout' mice have an increased incidence of tumors; and (vi) discovering that genetic complementation of MMR defective cells stabilizes the MMR deficiency-associated microsatellite instability. Models of carcinogenesis now must integrate the concepts of a MMR defect induced mutator phenotype (Loeb) with the concepts of multistep colon carcinogenesis (Fearon and Vogelstein) and clonal heterogeneity/selection (Nowell).

  4. Colorectal carcinogenesis-update and perspectives

    DEFF Research Database (Denmark)

    Raskov, Hans; Pommergaard, Hans-Christian; Burcharth, Jakob

    2014-01-01

    metabolism, high risk luminal environment, inflammation, as well as lifestyle factors such as diet, tobacco, and alcohol consumption. In recent years focus has turned towards the genetics and molecular biology of CRC and several interesting and promising correlations and pathways have been discovered...

  5. An Emergence Framework of Carcinogenesis.

    Science.gov (United States)

    Sigston, Elizabeth A W; Williams, Bryan R G

    2017-01-01

    Experimental paradigms provide the framework for the understanding of cancer, and drive research and treatment, but are rarely considered by clinicians. The somatic mutation theory (SMT), in which cancer is considered a genetic disease, has been the predominant traditional model of cancer for over 50 years. More recently, alternative theories have been proposed, such as tissue organization field theory (TOFT), evolutionary models, and inflammatory models. Key concepts within the various models have led to them being difficult to reconcile. Progressively, it has been recognized that biological systems cannot be fully explained by the physicochemical properties of their constituent parts. There is an increasing call for a 'systems' approach. Incorporating the concepts of 'emergence', 'systems', 'thermodynamics', and 'chaos', a single integrated framework for carcinogenesis has been developed, enabling existing theories to become compatible as alternative mechanisms, facilitating the integration of bioinformatics and providing a structure in which translational research can flow from both 'benchtop to bedside' and 'bedside to benchtop'. In this review, a basic understanding of the key concepts of 'emergence', 'systems', 'system levels', 'complexity', 'thermodynamics', 'entropy', 'chaos', and 'fractals' is provided. Non-linear mathematical equations are included where possible to demonstrate compatibility with bioinformatics. Twelve principles that define the 'emergence framework of carcinogenesis' are developed, with principles 1-10 encapsulating the key concepts upon which the framework is built and their application to carcinogenesis. Principle 11 relates the framework to cancer progression. Principle 12 relates to the application of the framework to translational research. The 'emergence framework of carcinogenesis' collates current paradigms, concepts, and evidence around carcinogenesis into a single framework that incorporates previously incompatible viewpoints

  6. Microbiota, Inflammation and Colorectal Cancer

    Directory of Open Access Journals (Sweden)

    Cécily Lucas

    2017-06-01

    Full Text Available Colorectal cancer, the fourth leading cause of cancer-related death worldwide, is a multifactorial disease involving genetic, environmental and lifestyle risk factors. In addition, increased evidence has established a role for the intestinal microbiota in the development of colorectal cancer. Indeed, changes in the intestinal microbiota composition in colorectal cancer patients compared to control subjects have been reported. Several bacterial species have been shown to exhibit the pro-inflammatory and pro-carcinogenic properties, which could consequently have an impact on colorectal carcinogenesis. This review will summarize the current knowledge about the potential links between the intestinal microbiota and colorectal cancer, with a focus on the pro-carcinogenic properties of bacterial microbiota such as induction of inflammation, the biosynthesis of genotoxins that interfere with cell cycle regulation and the production of toxic metabolites. Finally, we will describe the potential therapeutic strategies based on intestinal microbiota manipulation for colorectal cancer treatment.

  7. Dietary flavonoid intake and colorectal cancer risk in the European prospective investigation into cancer and nutrition (EPIC) cohort

    NARCIS (Netherlands)

    Zamora-Ros, Raul; Barupal, Dinesh K.; Rothwell, Joseph A.; Jenab, Mazda; Fedirko, Veronika; Romieu, Isabelle; Aleksandrova, Krasimira; Overvad, Kim; Kyrø, Cecilie; Tjønneland, Anne; Affret, Aurélie; His, Mathilde; Boutron-Ruault, Marie Christine; Katzke, Verena; Kühn, Tilman; Boeing, Heiner; Trichopoulou, Antonia; Naska, Androniki; Kritikou, Maria; Saieva, Calogero; Agnoli, Claudia; Santucci de Magistris, Maria; Tumino, Rosario; Fasanelli, Francesca; Weiderpass, Elisabete; Skeie, Guri; Merino, Susana; Jakszyn, Paula; Sánchez, Maria José; Dorronsoro, Miren; Navarro, Carmen; Ardanaz, Eva; Sonestedt, Emily; Ericson, Ulrika; Maria Nilsson, Lena; Bodén, Stina; Bas Bueno-de-Mesquita, H.; Peeters, Petra H.|info:eu-repo/dai/nl/074099655; Perez-Cornago, Aurora; Wareham, Nicholas J.; Khaw, Kay Thee; Freisling, Heinz; Cross, Amanda J.; Riboli, Elio; Scalbert, Augustin

    2017-01-01

    Flavonoids have been shown to inhibit colon cancer cell proliferation in vitro and protect against colorectal carcinogenesis in animal models. However, epidemiological evidence on the potential role of flavonoid intake in colorectal cancer (CRC) development remains sparse and inconsistent. We

  8. Diabetes promotes DMH-induced colorectal cancer by increasing the activity of glycolytic enzymes in rats.

    Directory of Open Access Journals (Sweden)

    Yanglei Jia

    Full Text Available The objective of the present study was to investigate the association between diabetes mellitus and colorectal carcinogenesis as well as the possible mechanism involved in this interaction. Diabetes rat models were induced with a low dose of STZ followed by a low dose of DMH to induce colorectal cancer. The formation of ACF in the colon and the incidence, number and size of tumors were measured. The activity of glycolytic enzymes in colonic tissues was also measured. The results demonstrated that both the total number of ACF and the number of foci that contain a different number of crypts were increased in diabetic rats. At the end of the experimental treatment, the incidence, number and size of tumors were also increased in diabetic rats. Overall, these data indicated that diabetes increased the risk of colorectal cancer. The activity of HK and PK in colonic tissues was increased in diabetic rats, whereas the activity of PDH was decreased. In addition, the activities of these enzymes in intratumor were higher than that of in peritumor. These data indicated that the high rate of glycolysis may play a role in colorectal carcinogenesis in diabetic rats.

  9. Exacerbation of colon carcinogenesis by Blastocystis sp.

    Science.gov (United States)

    Kumar, Suresh

    2017-01-01

    Colorectal cancer (CRC) is one the most commonly diagnosed cancers worldwide and the number is increasing every year. Despite advances in screening programs, CRC remains as the second leading cause of cancer deaths in the United States. Oxidative stress plays an important role in the molecular mechanisms of colorectal cancer (CRC) and has been shown to be associated with Blastocystis sp., a common intestinal microorganism. In the present study, we aimed to identify a role for Blastocystis sp. in exacerbating carcinogenesis using in vivo rat model. Methylene blue staining was used to identify colonic aberrant crypt foci (ACF) and adenomas formation in infected rats whilst elevation of oxidative stress biomarker levels in the urine and serum samples were evaluated using biochemical assays. Histological changes of the intestinal mucosa were observed and a significant number of ACF was found in Blastocystis sp. infected AOM-rats compared to the AOM-controls. High levels of urinary oxidative indices including advanced oxidative protein products (AOPP) and hydrogen peroxide were observed in Blastocystis sp. infected AOM-rats compared to the uninfected AOM-rats. Our study provides evidence that Blastocystis sp. has a significant role in enhancing AOM-induced carcinogenesis by resulting damage to the intestinal epithelium and promoting oxidative damage in Blastocystis sp. infected rats. PMID:28859095

  10. Dietary Patterns and Colorectal Adenomas in Lynch Syndrome The GEOLynch Cohort Study

    NARCIS (Netherlands)

    Botma, Akke; Vasen, Hans F. A.; van Duijnhoven, Franzel J. B.; Kleibeuker, Jan H.; Nagengast, Fokko M.; Kampman, Ellen

    2013-01-01

    BACKGROUND: Patients with Lynch syndrome (LS) have a high risk of developing colorectal cancer due to mutations in mismatch repair genes. Because dietary factors, alone and in combination, influence sporadic colorectal carcinogenesis, the association of dietary patterns with colorectal adenomas in

  11. Anticancer Effect of Lycopene in Gastric Carcinogenesis.

    Science.gov (United States)

    Kim, Mi Jung; Kim, Hyeyoung

    2015-06-01

    Gastric cancer ranks as the most common cancer and the second leading cause of cancer-related death in the world. Risk factors of gastric carcinogenesis include oxidative stress, DNA damage, Helicobacter pylori infection, bad eating habits, and smoking. Since oxidative stress is related to DNA damage, smoking, and H. pylori infection, scavenging of reactive oxygen species may be beneficial for prevention of gastric carcinogenesis. Lycopene, one of the naturally occurring carotenoids, has unique structural and chemical features that contributes to a potent antioxidant activity. It shows a potential anticancer activity and reduces gastric cancer incidence. This review will summarize anticancer effect and mechanism of lycopene on gastric carcinogenesis based on the recent experimental and clinical studies.

  12. Adamts18 deficiency promotes colon carcinogenesis by enhancing β-catenin and p38MAPK/ERK1/2 signaling in the mouse model of AOM/DSS-induced colitis-associated colorectal cancer.

    Science.gov (United States)

    Lu, Tiantian; Dang, Suying; Zhu, Rui; Wang, Ying; Nie, Zongying; Hong, Tao; Zhang, Wei

    2017-03-21

    ADAMTS18 is a novel tumor suppressor and is critical to the pathology of human colorectal cancer. However, the underlying mechanism is not clear. Here we generated an Adamts18-deficient mouse strain as an in vivo model to investigate the role of ADAMTS18 in the pathogenesis of colorectal cancer. In AOM/DSS-induced colitis-associated colorectal cancer, the deficiency of Adamts18 in mice resulted in enhanced tumorigenesis and colon inflammation that could be attributed in part to enhanced nuclear translocation of β-catenin and elevated expression of its downstream target genes, cyclin D1 and c-myc. Moreover, increased p38MAPK and ERK1/2 activities were detected in colon cancer cells from Adamts18-deficient mice. Further studies revealed that ADAMTS18 deficiency reduced intestinal E-cadherin levels in mice, which ultimately led to intestinal barrier dysfunction. These data indicate that Adamts18 deficiency enhances tumorigenesis and intestinal inflammation through elevated Wnt/β-catenin and p38MAPK/ERK1/2 signaling and promotes colon cancer in this mouse model.

  13. An Emergence Framework of Carcinogenesis

    Directory of Open Access Journals (Sweden)

    Elizabeth A. W. Sigston

    2017-09-01

    Full Text Available Experimental paradigms provide the framework for the understanding of cancer, and drive research and treatment, but are rarely considered by clinicians. The somatic mutation theory (SMT, in which cancer is considered a genetic disease, has been the predominant traditional model of cancer for over 50 years. More recently, alternative theories have been proposed, such as tissue organization field theory (TOFT, evolutionary models, and inflammatory models. Key concepts within the various models have led to them being difficult to reconcile. Progressively, it has been recognized that biological systems cannot be fully explained by the physicochemical properties of their constituent parts. There is an increasing call for a ‘systems’ approach. Incorporating the concepts of ‘emergence’, ‘systems’, ‘thermodynamics’, and ‘chaos’, a single integrated framework for carcinogenesis has been developed, enabling existing theories to become compatible as alternative mechanisms, facilitating the integration of bioinformatics and providing a structure in which translational research can flow from both ‘benchtop to bedside’ and ‘bedside to benchtop’. In this review, a basic understanding of the key concepts of ‘emergence’, ‘systems’, ‘system levels’, ‘complexity’, ‘thermodynamics’, ‘entropy’, ‘chaos’, and ‘fractals’ is provided. Non-linear mathematical equations are included where possible to demonstrate compatibility with bioinformatics. Twelve principles that define the ‘emergence framework of carcinogenesis’ are developed, with principles 1–10 encapsulating the key concepts upon which the framework is built and their application to carcinogenesis. Principle 11 relates the framework to cancer progression. Principle 12 relates to the application of the framework to translational research. The ‘emergence framework of carcinogenesis’ collates current paradigms, concepts, and evidence around

  14. [OBESITY AND ENDOMETRIAL CARCINOGENESIS].

    Science.gov (United States)

    Uchikova, E; Uchikov, P; Parahuleva, P

    2015-01-01

    Endometrial cancer is one of the main cancers occurring in industrialized countries. According to the National Cancer Registry in Bulgaria, cancer of the uterine body occupies 8.6% from all cancers in women and ranks second in frequency. It is found that over weight and obesity are a major risk factor for the development of endometrial cancer and the mortality associated with it. Adipose tissue is seen as endocrine organ, synthesizing so called adipocytokine - leptin, adiponectin, vistafin, that play a key role in the carcinogenesis of endometrial cancer and can be used as new markers for establishing the potential risk of this disease. The link between obesity, insulin resistance and endometrial cancer that has been proven, determines it as a socially significant disease. All this makes it necessary to clarify and specify the role of obesity in endometrial carcinogenesis and the development of strategies for the prevention and early diagnosis.

  15. Diet-induced obesity elevates colonic TNF-alpha in mice and is accompanied by an activation of Wnt signaling: a mechanism for obesity-associated colorectal cancer

    Science.gov (United States)

    Inflammation associated with obesity may play a role in colorectal carcinogenesis, but the underlying mechanism remains unclear. This study investigated whether the Wnt pathway, an intracellular signaling cascade that plays a critical role in colorectal carcinogenesis, is activated by obesity-induce...

  16. Contribución al estudio experimental del cancer III. Alteraciones de la corteza suprarrenal en la Carcinogenesis Química.

    Directory of Open Access Journals (Sweden)

    Oscar Miro-Quesada C

    1948-12-01

    Full Text Available 1.- Se hace un estudio crítico histo-químico funcional de la corteza suprarrenal en ratones homozigotes C3H (Strong sometidos a la cancerización química con 20-Metilcolantreno. 2.- Se describe un nuevo tipo de reacción funcional de dicha glándula bajo las condiciones experimentales empleadas, sugiriéndose la denominación de "atrofia-hiperactiva", en contraste con las alteraciones histo-químico funcionales de la corteza suprarrenal descritas por varios autores en animales portadores de injertos neoplásicos, las que corresponden al tipo de reacción funcional de la glándula caracterizado por "hipertrofia-hiperactiva". 3.- Los resultados obtenidos sugieren la intervención del sistema endocrino, via la corteza suprarrenal, durante el proceso de carcinogenesis química en el ratón homozigote de raza C3H (Strong.

  17. Early expression of the Helicase-Like Transcription Factor (HLTF/SMARCA3 in an experimental model of estrogen-induced renal carcinogenesis

    Directory of Open Access Journals (Sweden)

    Laurent Guy

    2006-06-01

    Full Text Available Abstract Background The Helicase-Like Transcription Factor (HLTF/SMARCA3 belongs to the family of SWI/SNF proteins that use the energy of ATP hydrolysis to remodel chromatin in a variety of cellular processes. Several SWI/SNF genes are disrupted in cancer, suggesting a role of tumor suppressor. Similarly, the HLTF gene was recently found to be inactivated by hypermethylation in a number of advanced colon and gastric tumors. However, other evidences indicated a 20-fold HLTF overexpression in cell lines derived from various neoplasms (ovary, breast, cervix, kidney.... Results In the present study, we investigated HLTF expression by immunohistochemistry in a model of kidney tumors induced by continuous administration of diethylstilbestrol to male Syrian golden hamsters. A strong labeling was already detected in small tumor buds, making HLTF an early cancer marker in this model. Although every cell stained for HLTF at this early stage, the number of HLTF-positive cells decreased to 10% with cancer progression, and these positive cells were dispersed in the tumor mass. HLTF expression was conserved in the HKT-1097 cell line established from kidney tumors, but again only 10% of positive cells were found in xenografts produced by HKT-1097 cells in nude mice. Conclusion In conclusion, our data suggest that HLTF gene activation is linked to initial steps of carcinogenesis in this model and should be investigated in early stages of other neoplasms.

  18. Colorectal Cancer: Genetics is Changing Everything.

    Science.gov (United States)

    Obuch, Joshua C; Ahnen, Dennis J

    2016-09-01

    Cancer is fundamentally a genetic disease caused by mutational or epigenetic alterations in DNA. There has been a remarkable expansion of the molecular understanding of colonic carcinogenesis in the last 30 years and that understanding is changing many aspects of colorectal cancer care. It is becoming increasingly clear that there are genetic subsets of colorectal cancer that have different risk factors, prognosis, and response to treatment. This article provides a general update on colorectal cancer and highlights the ways that genetics is changing clinical care. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. Dietary fiber, source foods and colorectal cancer risk: the Fukuoka Colorectal Cancer Study.

    Science.gov (United States)

    Uchida, Kazuhiro; Kono, Suminori; Yin, Guang; Toyomura, Kengo; Nagano, Jun; Mizoue, Tetsuya; Mibu, Ryuichi; Tanaka, Masao; Kakeji, Yoshihiro; Maehara, Yoshihiko; Okamura, Takeshi; Ikejiri, Koji; Futami, Kitaroh; Maekawa, Takafumi; Yasunami, Yohichi; Takenaka, Kenji; Ichimiya, Hitoshi; Terasaka, Reiji

    2010-10-01

    Despite much evidence from laboratory work, epidemiological evidence remains elusive regarding the role of dietary fiber in colorectal carcinogenesis. We investigated associations of dietary fiber and source foods with colorectal cancer risk in the Fukuoka Colorectal Cancer Study, a community-based case-control study. The study subjects were 816 incident cases of colorectal cancer and 815 community controls. Nutrient and food intakes were estimated on the basis of a computer-assisted interview regarding 148 dietary items. Odds ratios of colorectal cancer according to quintile categories of energy-adjusted intakes of dietary fiber and food groups were obtained with adjustment for non-dietary factors and dietary intakes of calcium and n-3 fatty acids. Total, soluble and insoluble dietary fibers were not measurably associated with overall risk or subsite-specific risk of colorectal cancer. By contrast, rice consumption was associated with a decreased risk of colorectal cancer (trend p = 0.03), particularly of distal colon and rectal cancer (trend p = 0.02), and high intake of non-rice cereals tended to be related to an increased risk of colon cancer (trend p = 0.07). There was no association between vegetable consumption and colorectal cancer, whereas individuals with the lowest intake of fruits tended to have an increased risk of colorectal cancer. The present study did not corroborate a protective association between dietary fiber and colorectal cancer, but suggested a decreased risk of distal colorectal cancer associated with rice consumption.

  20. Molecular biology in colorectal cancer.

    Science.gov (United States)

    Benito, Manuel; Díaz-Rubio, Eduardo

    2006-06-01

    Cancer is a genetic disease. Colorectal cancer is probably the type of cancer for which the most is known about the genes affected by cancer-causing mutations, their normal functions and their carcinogenic effects when mutated. Most cancer-causing mutations are somatic, occurring in the affected tissue during the course of carcinogenesis. However, most cancers also have a hereditary component that is caused by predisposing mutations that affect the germline, are heritable and contribute to the initiation of carcinogenesis. High-penetrance mutations confer predisposition to colorectal cancer mainly in Lynch syndrome (which involves mutations in mismatch-repair genes) and in familial adenomatous polyposis (which involves mutations in the APC tumour suppressor). Together, these conditions account for 5% or less of all cases of colorectal cancer. Low-penetrance mutations account for a high proportion of all the attributable risk of colorectal cancer, in both familial and sporadic cases. These mutations are more difficult to identify, but mainly due to the implementation of association studies, are increasingly being detected and characterized. The identification of both high- and low-penetrance mutations contributes significantly to our understanding of the molecular genetic processes occurring in cancer. This understanding facilitates the development of therapeutic drugs and preventive strategies.

  1. Systematically experimental investigation on carcinogenesis or tumorigenicity of VERO cell lines of different karyotypes in nude mice in vivo used for viral vaccine manufacture.

    Science.gov (United States)

    Zhang, De-Li; Ji, Liang; Li, Liu-Jin; Huang, Gao-Sheng

    2004-07-01

    Many cell lines used for vaccine production have a potentially strong tumorigenic character. Some of those routinely used need to be checked at different passage numbers for this characteristic. Using HeLa cell cultures as positive controls, and primary canine kidney cell (CKC) or feline kidney cell (FKC) cultures purified in vitro on passage three as negative controls, the tumorigenicity of VERO cell sublines was tested in 219 nude mice. The master cell stocks (MCS) and working cell banks (WCB) of eight strains of VERO African green monkey kidney cell (AGMKC) line used for canine, feline and mink vaccine preparation were established in China. The hypo-tetra-ploid JA or hyper-diploid KA strain of VERO line was highly tumorigenic. These data showed a variable chromosome karyotype of VERO line, and contraindicated the use of JA or KA strain of VERO line for the preparation of attenuated viral vaccines. JA or KA strain of VERO line could be a substitute for HeLa line as a positive-control malignant tumor (MT) cell model. The non-carcinogenic YB, JC, M and JB strains of VERO line were therefore selected for the preparation of modified live rabies viral vaccine in place of BHK-21. The cell sub-lines are comparatively stable in terms of their heritable characters, and show little significant changes between passages. In summary, we have found that: 1) the tumorigenicity of cell line is different among different-karyotypic cells; 2) it is the genetic characteristics of chromosomes of cell lines that determines their tumorigenicity, but with species-specific carcinogenicity; 3) the chromosome number variation of cell lines has positive relationship with their carcinogenesis; 4) highly variable strains of tumor cell line can be selected quickly and successfully in nude mice by alternate cultivation in vitro and in vivo. Malignant rhabdoid tumor (MRT) was evolved in nude mice inoculated with violently variable HeLa or VERO cells. The importance of assessing the

  2. Ginkgo biloba L. leaf extract offers multiple mechanisms in bridling N-methylnitrosourea - mediated experimental colorectal cancer.

    Science.gov (United States)

    Ahmed, Hanaa H; El-Abhar, Hanan S; Hassanin, Elsayed Abdul Khalik; Abdelkader, Noha F; Shalaby, Mohamed B

    2017-11-01

    In Egypt, colorectal cancer (CRC) is the 6th cancer in both gender and CRC rates are high in subjects under 40 years of age. This study goaled to determine the development of CRC using relevant biochemical markers and to elucidate the potent mechanism of Ginkgo biloba L. leaf extract in retrogression of experimental CRC. Adult male Sprague-Dawley rats were administered N-methylnitrosourea (N-MNU; 2mg in 0.5ml water/rat) intrarectally thrice a week for five weeks to induce CRC, followed by treatment with either 5-fluorouracil (5-FU; 12.5mg/kg, i.p.) or Ginkgo biloba L. leaf extract in a dose of 0.675 and 1.35g/kg, p.o. respectively. The developed tumor enhanced plasma TGF-β, and Bcl 2 , serum EGF, CEA, CCSA, and MMP-7 significantly. Also, gene expression analysis showed significant upregulation of colonic β-Catenin, K-ras and C-myc genes. Besides, immunohistochemical findings revealed significant increase in COX-2, cyclin D1 and survivin content in colon tissue. These data were further supported by the histological observations. Ginkgo biloba L. leaf extract-treated rats; particularly those treated with dose of 1.35g/kg, exhibited significant reduction in the aforementioned parameters and improvement in the histological organization of the colon tissue. The therapeutic effect of Ginkgo biloba L. leaf extract was comparable with that mediated by 5-FU. The current research proved that Ginkgo biloba L. leaf extract could suppress tumor cell proliferation, promote apoptosis, and mitigat inflammation in vivo. The amelioration of these key events might be linked with the inhibition of Wnt/β-Catenin signaling module. The outcomes of the present investigation encourage the use of Ginkgo biloba L. leaf extract as a complementary and alternative therapeutic approach to abate CRC. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  3. Inhibition of colon carcinogenesis by a standardized Cannabis sativa extract with high content of cannabidiol.

    Science.gov (United States)

    Romano, Barbara; Borrelli, Francesca; Pagano, Ester; Cascio, Maria Grazia; Pertwee, Roger G; Izzo, Angelo A

    2014-04-15

    Colon cancer is a major public health problem. Cannabis-based medicines are useful adjunctive treatments in cancer patients. Here, we have investigated the effect of a standardized Cannabis sativa extract with high content of cannabidiol (CBD), here named CBD BDS, i.e. CBD botanical drug substance, on colorectal cancer cell proliferation and in experimental models of colon cancer in vivo. Proliferation was evaluated in colorectal carcinoma (DLD-1 and HCT116) as well as in healthy colonic cells using the MTT assay. CBD BDS binding was evaluated by its ability to displace [(3)H]CP55940 from human cannabinoid CB1 and CB2 receptors. In vivo, the effect of CBD BDS was examined on the preneoplastic lesions (aberrant crypt foci), polyps and tumours induced by the carcinogenic agent azoxymethane (AOM) as well as in a xenograft model of colon cancer in mice. CBD BDS and CBD reduced cell proliferation in tumoral, but not in healthy, cells. The effect of CBD BDS was counteracted by selective CB1 and CB2 receptor antagonists. Pure CBD reduced cell proliferation in a CB1-sensitive antagonist manner only. In binding assays, CBD BDS showed greater affinity than pure CBD for both CB1 and CB2 receptors, with pure CBD having very little affinity. In vivo, CBD BDS reduced AOM-induced preneoplastic lesions and polyps as well as tumour growth in the xenograft model of colon cancer. CBD BDS attenuates colon carcinogenesis and inhibits colorectal cancer cell proliferation via CB1 and CB2 receptor activation. The results may have some clinical relevance for the use of Cannabis-based medicines in cancer patients. Copyright © 2013 Elsevier GmbH. All rights reserved.

  4. Cell proliferation in carcinogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Cohen, S.M.; Ellwein, L.B. (Univ. of Nebraska Medical Center, Omaha (USA))

    1990-08-31

    Chemicals that induce cancer at high doses in animal bioassays often fail to fit the traditional characterization of genotoxins. Many of these nongenotoxic compounds (such as sodium saccharin) have in common the property that they increase cell proliferation in the target organ. A biologically based, computerized description of carcinogenesis was used to show that the increase in cell proliferation can account for the carcinogenicity of nongenotoxic compounds. The carcinogenic dose-response relationship for genotoxic chemicals (such as 2-acetylaminofluorene) was also due in part to increased cell proliferation. Mechanistic information is required for determination of the existence of a threshold for the proliferative (and carcinogenic) response of nongenotoxic chemicals and the estimation of risk for human exposure.

  5. Does the application of Ankaferd Blood Stopper rectally have positive effects on the healing of colorectal anastomosis and prevention of anastomotic leakage? An experimental study.

    Science.gov (United States)

    Kuru, Serdar; Kismet, Kemal; Bag, Yusuf Murat; Barlas, Aziz Mutlu; Senes, Mehmet; Durak, Murat; Yumusak, Nihat; Urhan, Mustafa Kemal; Cavusoglu, Turgut; Pekcici, Recep

    2017-12-01

    The purpose of this experimental study was to evaluate the potential effects on the healing of colorectal anastomoses of the rectal administration of Ankaferd Blood Stopper (ABS). Thirty Wistar-Albino male rats were randomly separated into 3 groups. In the sham group, only laparotomy and colonic mobilization was performed. In the other 2 groups, colon transection and anastomosis were carried out. Saline (2 mL, 0.9% NaCl) was given rectally via a feeding tube for 10 days after the surgical procedure in the sham and control groups. In Group 3 (ABS group), the rats were treated with rectally administered ABS (2 mL/day) for 10 days. In all groups, after the measurement of bursting pressures, tissue samples were collected for the measurement of tissue hydroxyproline and prolidase levels, and for histopathological evaluation on postoperative day 11. The rectal administration of ABS showed positive effects on bursting pressures, tissue prolidase and hydroxyproline levels, and the histopathological findings of colonic anastomosis. The rectal application of ABS had positive effects on the healing of colorectal anastomosis. As a natural product, it may be used effectively and safely to achieve better healing results after colorectal anastomosis. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  6. Colorectal Cancer

    Science.gov (United States)

    ... rectum are part of the large intestine. Colorectal cancer occurs when tumors form in the lining of ... men and women. The risk of developing colorectal cancer rises after age 50. You're also more ...

  7. Pathogenesis and biomarkers of carcinogenesis in ulcerative colitis

    DEFF Research Database (Denmark)

    Thorsteinsdottir, Sigrun; Gudjonsson, Thorkell; Nielsen, Ole Haagen

    2011-01-01

    -driven mechanisms of DNA damage, including the generation and effects of reactive oxygen species, microsatellite instability, telomere shortening and chromosomal instability, are reviewed, as are the molecular responses to genomic stress. We also discuss how these mechanisms can be translated into usable biomarkers....... Although progress has been made in the understanding of inflammation-driven carcinogenesis, markers based on these findings possess insufficient sensitivity or specificity to be usable as reliable biomarkers for risk of colorectal cancer development in patients with ulcerative colitis. However, screening...

  8. Folate-related nutrients, genetic polymorphisms, and colorectal cancer risk: the fukuoka colorectal cancer study.

    Science.gov (United States)

    Morita, Makiko; Yin, Guang; Yoshimitsu, Shin-ichiro; Ohnaka, Keizo; Toyomura, Kengo; Kono, Suminori; Ueki, Takashi; Tanaka, Masao; Kakeji, Yoshihiro; Maehara, Yoshihiko; Okamura, Takeshi; Ikejiri, Koji; Futami, Kitaroh; Maekawa, Takafumi; Yasunami, Yohichi; Takenaka, Kenji; Ichimiya, Hitoshi; Terasaka, Reiji

    2013-01-01

    One-carbon metabolism plays an important role in colorectal carcinogenesis. Meta-analyses have suggested protective associations of folate and vitamin B6 intakes with colorectal cancer primarily based on studies in Caucasians, and genetic polymorphisms pertaining to the folate metabolism have been a matter of interest. Less investigated are the roles of methionine synthase (MTR) and thymidylate synthetase (TS) polymorphisms in colorectal carcinogenesis. In a study of 816 cases and 815 community controls in Japan, we investigated associations of dietary intakes of folate, methionine, vitamin B2, vitamin B6, and vitamin B12 with colorectal cancer risk. The associations with MTR 2756A>G, MTRR 66A>G, and TSER repeat polymorphism were examined in 685 cases and 778 controls. Methionine and vitamin B12 intakes were inversely associated with colorectal cancer risk, but the associations were totally confounded by dietary calcium and n-3 fatty acids. The other nutrients showed no association with the risk even without adjustment for calcium and n-3 fatty acids. The TSER 2R allele was dose-dependently associated with an increased risk. The MTR and MTRR polymorphisms were unrelated to colorectal cancer risk. There was no measurable gene-gene or gene-nutrient interaction, but increased risk associated with the TSER 2R allele seemed to be confined to individuals with high folate status. This study does not support protective associations for folate and vitamin B6. The TSER 2R allele may confer an increased risk of colorectal cancer. The role of the TSER polymorphism in colorectal carcinogenesis may differ by ethnicity.

  9. High occurrence of Fusobacterium nucleatum and Clostridium difficile in the intestinal microbiota of colorectal carcinoma patients

    OpenAIRE

    Fukugaiti,Márcia H.; Aline Ignacio; Miriam R. Fernandes; Ulysses Ribeiro Júnior; Viviane Nakano; Avila-Campos, Mario J.

    2015-01-01

    Abstract Colorectal carcinoma is considered the fourth leading cause of cancer deaths worldwide. Several microorganisms have been associated with carcinogenesis, including Enterococcus spp., Helicobacter pylori, enterotoxigenic Bacteroides fragilis, pathogenic E. coli strains and oral Fusobacterium. Here we qualitatively and quantitatively evaluated the presence of oral and intestinal microorganisms in the fecal microbiota of colorectal cancer patients and healthy controls. Seventeen patients...

  10. K-ras oncogene mutations in sporadic colorectal cancer in The Netherlands Cohort Study

    NARCIS (Netherlands)

    Brink, M.; Goeij, A.F.P.M. de; Weijenberg, M.P.; Roemen, G.M.J.M.; Lentjes, M.H.F.M.; Pachen, M.M.M.; Smits, K.M.; Bruïne, A.P. de; Goldbohm, R.A.; Brandt, P.A. van den

    2003-01-01

    Activation of K-ras oncogene has been implicated in colorectal carcinogenesis, being mutated in 30-60% of the adenocarcinomas. In this study, 737 incident colorectal cancer (CRC) patients, originating from 120 852 men and women (55-69 years at baseline) participating in the Netherlands Cohort Study

  11. Biomarkers Related to One-Carbon Metabolism as Potential Risk Factors for Distal Colorectal Adenomas

    NARCIS (Netherlands)

    Vogel, de S.; Schneede, J.; Ueland, P.M.; Vollset, S.E.; Meyer, K.; Fredriksen, A.; Midttun, O.; Bjorge, T.; Kampman, E.; Bretthauer, M.; Hoff, G.

    2011-01-01

    Background: Efficient one-carbon metabolism, which requires adequate supply of methyl group donors and B-vitamins, may protect against colorectal carcinogenesis. However, plasma folate and vitamins B2 and B12 have inconsistently been associated with colorectal cancer risk, and there have been no

  12. Biomarkers related to one-carbon metabolism as potential risk factors for distal colorectal adenomas

    NARCIS (Netherlands)

    Vogel, S. de; Schneede, J.; Ueland, P.M.; Vollset, S.E.; Meyer, K.; Fredriksen, A.; Midttun, O.; Bjorge, T.; Kampman, E.; Bretthauer, M.; Hoff, G.

    2011-01-01

    BACKGROUND: Efficient one-carbon metabolism, which requires adequate supply of methyl group donors and B-vitamins, may protect against colorectal carcinogenesis. However, plasma folate and vitamins B2 and B12 have inconsistently been associated with colorectal cancer risk, and there have been no

  13. Genetic variants of methyl metabolizing enzymes and epigenetic regulators: Associations with promoter CpG island hypermethylation in colorectal cancer

    NARCIS (Netherlands)

    Vogel, S. de; Wouters, K.A.D.; Gottschalk, R.W.H.; Schooten, F.J. van; Goeij, A.F.P.M. de; Bruïne, A.P. de; Goldbohm, R.A.; Brandt, P.A. van den; Weijenberg, M.P.; Engeland, M. van

    2009-01-01

    Aberrant DNA methylation affects carcinogenesis of colorectal cancer. Folate metabolizing enzymes may influence the bioavailability of methyl groups, whereas DNA and histone methyltransferases are involved in epigenetic regulation of gene expression. We studied associations of genetic variants of

  14. A Method for Serial Tissue Processing and Parallel Analysis of Aberrant Crypt Morphology, Mucin Depletion, and Beta-Catenin Staining in an Experimental Model of Colon Carcinogenesis

    Directory of Open Access Journals (Sweden)

    McGinley John N

    2010-05-01

    Full Text Available Abstract The use of architectural and morphological characteristics of cells for establishing prognostic indicators by which individual pathologies are assigned grade and stage is a well-accepted practice. Advances in automated micro- and macroscopic image acquisition and digital image analysis have created new opportunities in the field of prognostic assessment; but, one area in experimental pathology, animal models for colon cancer, has not taken advantage of these opportunities. This situation is primarily due to the methods available to evaluate the colon of the rodent for the presence of premalignant and malignant pathologies. We report a new method for the excision and processing of the entire colon of the rat and illustrate how this procedure permitted the quantitative assessment of aberrant crypt foci (ACF, a premalignant colon pathology, for characteristics consistent with progression to malignancy. ACF were detected by methylene blue staining and subjected to quantitative morphometric analysis. Colons were then restained with high iron diamine–alcian blue for assessment of mucin depletion using an image overlay to associate morphometric data with mucin depletion. The subsequent evaluation of ACF for beta-catenin staining is also demonstrated. The methods described are particularly relevant to the screening of compounds for cancer chemopreventive activity. Additional file 1 Click here for file

  15. Prevention and Treatment of Experimental Estrogen Receptor – Negative Mammary Carcinogenesis by the Synthetic Triterpenoid CDDO-Methyl Ester and the Rexinoid LG100268

    Science.gov (United States)

    Liby, Karen; Risingsong, Renee; Royce, Darlene B.; Williams, Charlotte R.; Yore, Mark M.; Honda, Tadashi; Gribble, Gordon W.; Lamph, William W.; Vannini, Nicola; Sogno, Ilaria; Albini, Adriana; Sporn, Michael B.

    2016-01-01

    Purpose To test whether the triterpenoid 2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oic acid methyl ester (CDDO-Me) and the rexinoid LG100268 (268) prevent the formation of estrogen receptor (ER) – negative mammary tumors or either arrest the growth or cause regression of established tumors in MMTV-neu mice. Experimental Design For prevention, mice were fed control diet, CDDO-Me (60 mg/kg diet), 268 (20 mg/kg diet), or the combination for 45 weeks. For treatment, mice with established tumors at least 4 mm in diameter were fed control diet, CDDO-Me (100 mg/kg diet), 268 (60 mg/kg diet), or the combination for 4 weeks. Results CDDO-Me and 268 significantly delayed the development of ER-negative tumors, with a 14- and 24-week delay, respectively, compared with the control group for the time required to reach 50% tumor incidence. The combination of CDDO-Me and 268 was significantly more potent than the individual drugs, as only one tumor was found in the combination group, after 45 weeks on diet, at which time all control animals had tumors. Treating established tumors with CDDO-Me arrested the growth of 86% of the tumors, and 268 induced tumor regression in 85% of tumors. CDDO-Me and 268 target different signaling pathways and cell types. CDDO-Me inhibited constitutive STAT3 phosphorylation and the degradation of IKBα in ER-negative breast cancer cells, whereas 268 blocked IKBα degradation and the release of interleukin-6 in RAW264.7 macrophage-like cells, inhibited the ability of endothelial cells to organize into networks, and blocked angiogenesis in vivo. Conclusions CDDO-Me and 268 are useful as individual drugs to prevent ER-negative mammary tumorigenesis and to treat established tumors. They synergize when used in combination for prevention. PMID:18628471

  16. Molecular Cytogenetics: Genomic Imbalances in Colorectal Cancer and their Clinical Impact

    Directory of Open Access Journals (Sweden)

    Marian Grade

    2006-01-01

    Full Text Available Chromosomal aberrations play a dominant role in colorectal carcinogenesis. The application of fluorescence in situ hybridization (FISH based techniques such as comparative genomic hybridization (CGH and spectral karyotyping (SKY revealed that colorectal carcinomas are characterized by a specific pattern of chromosomal imbalances which sequentially accumulate during cancer progression. This review aims to summarize molecular cytogenetic studies, provides a background on the functional relevance of chromosomal aberrations for colorectal cancer progression and discusses their potential clinical impact.

  17. Molecular biology of nickel carcinogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Costa, M. [Nelson Institute of Environmental Medicine and the Kaplan Comprehensive Cancer Center, New York University Medical Center, NY (United States)

    1998-06-01

    The molecular mechanisms of nickel carcinogenesis are discussed and reviewed with emphasis on work done in my laboratory. The most important determinant of nickel carcinogenesis is the ability of the nickel ion to reach relevant targets for carcinogenesis, which involves chromatin and depends on the ability of the nickel compound to enter cells. The mechanisms that regulate the phagocytosis and intracellular dissolution of the highly carcinogenic particulate nickel compounds are discussed, as is the ability of these nickel compounds to enhance the DNA methylation pattern and turn off the expression of critical tumor suppressor genes. These findings show these nickel compounds to be a somewhat unique class of carcinogens. (orig.) (orig.) With 3 figs., 4 tabs., 31 refs.

  18. Evolving Concepts in Lung Carcinogenesis

    Science.gov (United States)

    Gomperts, Brigitte N.; Spira, Avrum; Massion, Pierre P.; Walser, Tonya C.; Wistuba, Ignacio I.; Minna, John D.; Dubinett, Steven M.

    2012-01-01

    Lung carcinogenesis is a complex, stepwise process that involves the acquisition of genetic mutations and epigenetic changes that alter cellular processes, such as proliferation, differentiation, invasion, and metastasis. Here, we review some of the latest concepts in the pathogenesis of lung cancer and highlight the roles of inflammation, the “field of cancerization,” and lung cancer stem cells in the initiation of the disease. Furthermore, we review how high throughput genomics, transcriptomics, epigenomics, and proteomics are advancing the study of lung carcinogenesis. Finally, we reflect on the potential of current in vitro and in vivo models of lung carcinogenesis to advance the field and on the areas of investigation where major breakthroughs will lead to the identification of novel chemoprevention strategies and therapies for lung cancer. PMID:21500122

  19. Defining the role of polyamines in colon carcinogenesis using mouse models

    Directory of Open Access Journals (Sweden)

    Natalia A Ignatenko

    2011-01-01

    Full Text Available Genetics and diet are both considered important risk determinants for colorectal cancer, a leading cause of death in the US and worldwide. Genetically engineered mouse (GEM models have made a significant contribution to the characterization of colorectal cancer risk factors. Reliable, reproducible, and clinically relevant animal models help in the identification of the molecular events associated with disease progression and in the development of effictive treatment strategies. This review is focused on the use of mouse models for studying the role of polyamines in colon carcinogenesis. We describe how the available mouse models of colon cancer such as the multiple intestinal neoplasia (Min mice and knockout genetic models facilitate understanding of the role of polyamines in colon carcinogenesis and help in the development of a rational strategy for colon cancer chemoprevention.

  20. Serum cell-free DNA concentration in BALB/c mice with azoxymethane-dextran sodium sulfate-induced colorectal cancer

    Directory of Open Access Journals (Sweden)

    Virhan Novianry

    2015-04-01

    Full Text Available Background: Colorectal cancer is the third most common cancer in the United States with a mortality rate ranked second in 2012. Early diagnosis such as detection of DNA in serum or faeces at the polyp stage, will reduce colorectal cancer mortality. This study was conducted to analyze the concentration of cell-free DNA (cfDNA as a tumor marker in colorectal carcinogenesis by using blood serum samples from BALB/c mice previously induced by azoxymethane (AOM and promoted by dextran sodium sulfate (DSS.Methods: This experimental animal study used 6 BALB/c mice which had serial intervention in a certain time frame. The first serum samples were taken before induction of carcinogenesis (week-0; then AOM induction of carcinogenesis followed and the second sampling one week after AOM intervention (week-1. Subsequently, promotion of carcinogenesis followed with DSS and the third sampling one week after this intervention (week-2. The fourth sampling was 5 weeks after AOM-DSS intervention (week-6. Quantification of the serum cfDNA was performed with SYBR-Green II fluorescence using Rotor Gene 6000 as a reference. Histopathological examination verified induction of carcinogenesis. For statistical analysis paired T-test was used.Results: Concentration of serum cfDNA showed significant difference between sampling group at week-0 (1238.49 ± 674.84 pg/µL and sampling group at week-6 (2244.04 ± 726.57 pg/µL the latter group showing pre-cancerous histopathology. Slightly increased cfDNA at week-1 with AOM induction (1358.57 ± 803.81 pg/µL and week-2 after DSS promotion (1317.23 ± 735.92 pg/µL were not significantly different from week-0 samples.Conclusion: The concentration of cfDNA in the serum of BALB/c mice 5 weeks after AOM induction of carcinogenesis and DSS promotion is significantly higher than before induction.

  1. Fas Ligand Expression in Lynch Syndrome-Associated Colorectal Tumours

    NARCIS (Netherlands)

    Koornstra, Jan J.; de Jong, Steven; Boersma-van Eck, Wietske; Zwart, Nynke; Hollema, Harry; de Vries, Elisabeth G. E.; Kleibeuker, Jan H.

    Fas Ligand (FasL) expression by cancer cells may contribute to tumour immune escape via the Fas counterattack against tumour-infiltrating lymphocytes (TILs). Whether this plays a role in colorectal carcinogenesis in Lynch syndrome was examined studying FasL expression, tumour cell apoptosis and

  2. Dietary factors and truncating APC mutations in sporadic colorectal adenomas.

    NARCIS (Netherlands)

    Diergaarde, B.; Tiemersma, E.W.; Braam, H.; Muijen, G.N.P. van; Nagengast, F.M.; Kok, F.J.; Kampman, E.

    2005-01-01

    Inactivating mutations in APC are thought to be early, initiating events in colorectal carcinogenesis. To gain insight into the relationship between diet and inactivating APC mutations, we evaluated associations between dietary factors and the occurrence of these mutations in a Dutch case-control

  3. Dietary factors and Truncating APC Mutations in Sporadic Colorectal Adenomas

    NARCIS (Netherlands)

    Diergaarde, B.; Tiemersma, E.W.; Braam, H.; Muijen, van G.N.P.; Nagengast, F.M.; Kok, F.J.; Kampman, E.

    2005-01-01

    Inactivating mutations in APC are thought to be early, initiating events in colorectal carcinogenesis. To gain insight into the relationship between diet and inactivating APC mutations, we evaluated associations between dietary factors and the occurrence of these mutations in a Dutch case-control

  4. The Mendelian colorectal cancer syndromes.

    Science.gov (United States)

    Tomlinson, Ian

    2015-11-01

    A small minority of colorectal cancers (CRCs) (≤5%) are caused by a single, inherited faulty gene. These diseases, the Mendelian colorectal cancer (CRC) syndromes, have been central to our understanding of colorectal carcinogenesis in general. Most of the approximately 13 high-penetrance genes that predispose to CRC primarily predispose to colorectal polyps, and each gene is associated with a specific type of polyp, whether conventional adenomas (APC, MUTYH, POLE, POLD1, NTHL1), juvenile polyps (SMAD4, BMPR1A), Peutz-Jeghers hamartomas (LKB1/STK11) and mixed polyps of serrated and juvenile types (GREM1). Lynch syndrome (MSH2, MLH1, MSH6, PMS2), by contrast, is associated primarily with cancer risk. Major functional pathways are consistently inactivated in the Mendelian CRC syndromes: certain types of DNA repair (proofreading of DNA replication errors, mismatch repair and base excision repair) and signalling (bone morphogenetic protein (BMP), Wnt signalling and mTOR). The inheritance of the CRC syndromes also varies: most are dominant but some of the DNA repair deficiencies are recessive. Some of the Mendelian CRC genes are especially important because they play a role through somatic inactivation in sporadic CRC (APC, MLH1, SMAD4, POLE). Additional Mendelian CRC genes may remain to be discovered and searches for these genes are ongoing, especially in patients with multiple adenomas and hyperplastic polyps. © The Author(s) 2015.

  5. Radiation carcinogenesis: radioprotectors and photosensitizers

    Energy Technology Data Exchange (ETDEWEB)

    Fry, R.J.M.

    1982-01-01

    This paper outlines 1) some of the salient features of radiation carcinogenesis that are pertinent to the questions of how the carcinogenic effects might be influenced, 2) the effects of radioprotectors on ionizing radiation-induced cancer, and 3) the effect of photosensitizers on UVR-induced skin cancer.

  6. Microsatellite Instability of Gastric and Colorectal Cancers as a Predictor of Synchronous Gastric or Colorectal Neoplasms.

    Science.gov (United States)

    Kim, Young Beak; Lee, Sun-Young; Kim, Jeong Hwan; Sung, In-Kyung; Park, Hyung Seok; Shim, Chan Sup; Han, Hye Seung

    2016-03-01

    Microsatellite instability (MSI) plays a crucial role in gastrointestinal carcinogenesis. The aim of this study was to clarify whether MSI is a useful marker for predicting synchronous gastric and colorectal neoplasms. Consecutive patients who underwent both esophagogastroduodenoscopy and colonoscopy before the resection of gastric or colorectal cancers were included. MSI was analyzed using two mononucleotide and three dinucleotide markers. In total, 434 gastric cancers (372 microsatellite stability [MSS], 21 low incidence of MSI [MSI-L], and 41 high incidence of MSI [MSI-H]) and 162 colorectal cancers (138 MSS, 9 MSI-L, and 15 MSI-H) were included. Patients with MSI gastric cancer had a higher prevalence of synchronous colorectal cancer, colorectal adenoma, and gastric adenoma than those with MSS gastric cancers (4.8% vs 0.5%, p=0.023; 11.3% vs 3.2%, p=0.011; 3.2% vs 1.2%, p=0.00, respectively). The prevalence of synchronous colorectal adenomas was highest in MSI-L gastric cancers (19.0%), compared with MSI-H (7.3%) or MSS (3.2%) gastric cancers (p=0.002). In addition, there were no significant differences in the prevalence rates of synchronous colorectal adenoma among the MSI-H (13.3%), MSI-L (11.1%), and MSS (12.3%) colorectal cancers (p=0.987). The presence of MSI in gastric cancer may be a predictor of synchronous gastric and colorectal neoplasms, whereas MSI in colorectal cancer is not a predictor of synchronous colorectal adenoma.

  7. Microsatellite Instability of Gastric and Colorectal Cancers as a Predictor of Synchronous Gastric or Colorectal Neoplasms

    Science.gov (United States)

    Kim, Young Beak; Lee, Sun-Young; Kim, Jeong Hwan; Sung, In-Kyung; Park, Hyung Seok; Shim, Chan Sup; Han, Hye Seung

    2016-01-01

    Background/Aims Microsatellite instability (MSI) plays a crucial role in gastrointestinal carcinogenesis. The aim of this study was to clarify whether MSI is a useful marker for predicting synchronous gastric and colorectal neoplasms. Methods Consecutive patients who underwent both esophagogastroduodenoscopy and colonoscopy before the resection of gastric or colorectal cancers were included. MSI was analyzed using two mononucleotide and three dinucleotide markers. Results In total, 434 gastric cancers (372 microsatellite stability [MSS], 21 low incidence of MSI [MSI-L], and 41 high incidence of MSI [MSI-H]) and 162 colorectal cancers (138 MSS, 9 MSI-L, and 15 MSI-H) were included. Patients with MSI gastric cancer had a higher prevalence of synchronous colorectal cancer, colorectal adenoma, and gastric adenoma than those with MSS gastric cancers (4.8% vs 0.5%, p=0.023; 11.3% vs 3.2%, p=0.011; 3.2% vs 1.2%, p=0.00, respectively). The prevalence of synchronous colorectal adenomas was highest in MSI-L gastric cancers (19.0%), compared with MSI-H (7.3%) or MSS (3.2%) gastric cancers (p=0.002). In addition, there were no significant differences in the prevalence rates of synchronous colorectal adenoma among the MSI-H (13.3%), MSI-L (11.1%), and MSS (12.3%) colorectal cancers (p=0.987). Conclusions The presence of MSI in gastric cancer may be a predictor of synchronous gastric and colorectal neoplasms, whereas MSI in colorectal cancer is not a predictor of synchronous colorectal adenoma. PMID:26087787

  8. Expression of insulin-like growth factor system components in colorectal tissue and its relation with serum IGF levels.

    NARCIS (Netherlands)

    Vrieling, A.; Voskuil, D.W.; Bosma, A.; Majoor, D.M.; Doorn, J. van; Cats, A.; Depla, A.C.; Timmer, R.; Witteman, B.J.; Wesseling, J.; Kampman, E.; Veer, L.J. van 't

    2009-01-01

    CONTEXT: The insulin-like growth factor (IGF)-system has been implicated in colorectal tumor carcinogenesis. Although both tumor expression levels and serum concentrations of IGF-system components are related to colorectal cancer risk, it is unknown whether IGF levels in tissue and serum are

  9. Expression of insulin-like growth factor system components in colorectal tissue and its relation with serum IGF levels

    NARCIS (Netherlands)

    Vrieling, A.; Voskuil, D.W.; Bosma, A.; Majoor, D.M.; Doorn, van J.; Cats, A.; Depla, A.; Timmer, R.; Witteman, B.J.M.; Wesseling, J.; Kampman, E.; van't Veer, L.J.

    2009-01-01

    Context: The insulin-like growth factor (IGF)-system has been implicated in colorectal tumor carcinogenesis. Although both tumor expression levels and serum concentrations of IGF-system components are related to colorectal cancer risk, it is unknown whether IGF levels in tissue and serum are

  10. Transgenerational teratogenesis and carcinogenesis by radiation

    Energy Technology Data Exchange (ETDEWEB)

    Nomura, Taisei [Osaka Univ., Suita (Japan). Graduate School of Medicine

    2000-07-01

    This paper thoroughly reviews studies on transgenerational teratogenesis and carcinogenesis induced by radiation and summarizes currently available data from animal studies. The discussions focus on the incidence of tumors, malformations, and mutations in the offspring after parental exposure to radiation, as well as estimated relative risks of congenital malformations and stillbirths in the offspring after parental X-ray exposure. The data suggest that different types of tumors are induced in offspring, because of strain differences in the experimental animals. The results of epidemiological studies in human populations, such as the children of atomic bomb survivors, conflict with the findings in animal studies. The author points to the following reasons for the differences between the results in animals and humans: differences in radiation doses, timing of exposure, and genetic predisposition, etc. While pointing out issues that need to be investigated further, the author indicates that clear strain differences exist in types of tumors induced and in tumor incidences in the offspring of animals that were irradiated before the offspring were conceived, and that genetic predisposition is therefore important in transgenerational carcinogenesis. (K.H.)

  11. Hesperidin induces apoptosis and triggers autophagic markers through inhibition of Aurora-A mediated phosphoinositide-3-kinase/Akt/mammalian target of rapamycin and glycogen synthase kinase-3 beta signalling cascades in experimental colon carcinogenesis.

    Science.gov (United States)

    Saiprasad, Gowrikumar; Chitra, Palanivel; Manikandan, Ramar; Sudhandiran, Ganapasam

    2014-09-01

    Abnormalities in the homeostasis mechanisms involved in cell survival and apoptosis are contributing factors for colon carcinogenesis. Interventions of these mechanisms by pharmacologically safer agents gain predominance in colon cancer prevention. We previously reported the chemopreventive efficacy of hesperidin against colon carcinogenesis. In the present study, we aimed at investigating the potential of hesperidin over the abrogated Aurora-A coupled pro-survival phosphoinositide-3-kinase (PI3K)/Akt signalling cascades. Further, the role of hesperidin over apoptosis and mammalian target of rapamycin (mTOR) mediated autophagic responses were studied. Azoxymethane (AOM) induced mouse model of colon carcinogenesis was involved in this study. Hesperidin treatment was provided either in initiation/post-initiation mode respectively. Hesperidin significantly altered AOM mediated anti-apoptotic scenario by modulating Bax/Bcl-2 ratio together with enhanced cytochrome-c release and caspase-3, 9 activations. In addition, hesperidin enhanced p53-p21 axis with concomitant decrease in cell cycle regulator. Hesperidin treatment caused significant up-regulation of tumour suppressor phosphatase and tensin homologue (PTEN) with a reduction in the expression of AOM mediated p-PI3K and p-Akt. Additionally, hesperidin administration exhibited inhibition against p-mTOR expression which in turn led to stimulation of autophagic markers Beclin-1 and LC3-II. Aurora-A an upstream regulator of PI3K/Akt pathway was significantly inhibited by hesperidin. Furthermore, hesperidin administration restored glycogen synthase kinase-3 beta (GSK-3β) activity which in turn prevented the accumulation of oncoproteins β-catenin, c-jun and c-myc. Taken together, hesperidin supplementation initiated apoptosis via targeted inhibition of constitutively activated Aurora-A mediated PI3K/Akt/GSK-3β and mTOR pathways coupled with autophagic stimulation against AOM induced colon carcinogenesis. Copyright

  12. Colorectal Cancer

    Science.gov (United States)

    ... detected by optical colonoscopy. Virtual colonoscopy uses virtual reality technology to produce three-dimensional images of the ... that if current trends in reducing risk factors, increased screening, and better treatment persist, colorectal cancer mortality ...

  13. Effect of defunctionalization on colon carcinogenesis in the rat Efecto de la desfuncionalización colónica en un modelo experimental de cáncer de colon

    Directory of Open Access Journals (Sweden)

    S. Pérez-Holanda

    2006-09-01

    Full Text Available Objective: to examine the effect of fecal absence on experimental colon carcinogenesis in both male and female rats. Material and methods: a total of 138 10-week-old Sprague-Dawley, male and female rats were divided into five groups: A 20 rats, no treatment; B 26 rats, colonic defunctionalization; C 30 rats, 18 weekly doses of dimethylhydrazine (DMH, 21 mg/kg body weight each, from the beginning of the study; D 20 rats, ethylen-diamine-tetraacetic acid for 18 weeks; and E 42 rats, same surgical procedure as rats in group B plus DMH injections at the same doses as rats in group C. Animals were sacrificed after 25-27 weeks. Number of tumors, their location, and pathological findings were all compared between groups. Results: no tumors developed in the dimethylhydrazine-free groups. No differences were obtained either in number of tumors or tumors per rat for group C as compared to group E. Fecal absence was associated with smaller-sized tumors (p = 0.007, greater numbers of non-mucinous tumors (p = 0.00009, better differentiation (p = 0.0054, and lesser penetration into the wall (p = 0.015 for group E as compared to group C. In the dimethylhydrazine group, fecal absence altered the number of tumors developing in males as compared to female rats (p = 0.025. Moreover, this fecal absence showed no inhibitory effect on right colonic tumors (p = 0.0065. Conclusions: fecal absence alters the DMH-carcinogenic pattern in the defunctionalized colon when using an experimental model in both male and female rats.Objetivo: examinar el efecto de la ausencia fecal en la aparición y desarrollo de la carcinogénesis colónica en ratas de ambos sexos. Material y métodos: ciento treinta y ocho ratas "Sprague-Dawley' de 10 semanas de vida, de ambos sexos, divididas en 5 grupos: A 20 ratas, sin tratamiento; B 26 ratas, con una desfuncionalización colónica; C 30 ratas, 18 dosis semanales de 21 mg/kg peso de dimetilhidracina (DMH desde el principio del estudio; D 20

  14. Epigenetic mechanisms of nickel carcinogenesis.

    Science.gov (United States)

    Salnikow, K; Costa, M

    2000-01-01

    This article considers the mechanism of nickel carcinogenesis, focusing primarily on the epigenetic changes associated with exposure of cells to carcinogenic nickel compounds. We discuss the delivery of nickel in the cell and contrast the genetic and epigenetic changes that have occurred. Within the epigenetic effects, alteration in the levels of transcription factors, such as ATF-1, p53, HIF-1, HIF-1alpha, and NFkappaB, are considered. The relationship between nickel and calcium metabolism and the role it plays in nickel carcinogenesis is also considered, as are reactive oxygen species and the interactions of nickel with proteins. We discuss these epigenetic discussions in light of the effects that nickel has on inducing DNA methylation in cells. It is of interest that nickel induces both a variety of signaling pathways as well as genes that seem to be important for the survival of cancer cells. It is also interesting that the same genes induced or repressed by nickel are similarly overexpressed or not expressed in nickel-transformed cells. It is suggested that this may represent a selection process crucial to the nickel carcinogenesis process.

  15. Using Positron Emission Tomography with [18F]FDG to Predict Tumor Behavior in Experimental Colorectal Cancer

    Directory of Open Access Journals (Sweden)

    Bryan M. Burt

    2001-01-01

    Full Text Available This study investigates the relationship between FDG uptake as determined by positron emission tomography (PET imaging and rates of tumor growth, cellular GLUT1 transporter density, and the activities of hexokinase and glucose-6-phosphatase in a solid tumor implant model. Five different human colorectal xenografts of different growth properties were implanted in athymic rats and evaluated by dynamic 18F-FDG-PET. The phosphorylating and dephosphorylating activities of the key glycolytic enzymes, hexokinase and glucose-6-phosphatase, were measured in these tumor types by spectrophotometric assays and the expression of GLUT1 glucose transporter protein was determined by immunohistochemistry. Correlations among FDG accumulation, hexokinase activity, and tumor doubling time are reported in these colon xenografts. The results indicate that the activity of tumor hexokinase may be a marker of tumor growth rate that can be determined by 18F-FDG-PET imaging. PET scanning may not only be a useful tool for staging patients for extent of disease, but may provide important prognostic information concerning the proliferative rates of malignancies.

  16. Effects of Promotional Materials on Attitudes and Fear towards Colorectal Cancer Screening among Chinese Older Adults: An Experimental Study.

    Science.gov (United States)

    Leung, Doris Y P; Chen, Joanne M T; Lou, Vivian W Q; Wong, Eliza M L; Chan, Aileen W K; So, Winnie K W; Chan, Carmen W H

    2017-07-13

    Colorectal cancer (CRC) screening is a cost-effective prevention and control strategy. However, the promotion of CRC screening for older adults may be difficult because reading CRC prevention information may evoke embarrassment, fear, and anxiety towards the screening procedure and cancer diagnosis. This study aims to (1) examine the effects of three promotional materials for CRC screening on the attitudes toward CRC screening tests (screening interest, screening effectiveness, and trust in the screening results) and cancer fear, and (2) to explore the interaction effect of cancer fear with screening effectiveness and trust in the screening results on screening interest of the three screening tests (fecal occult blood test (FOBT), flexible sigmoidoscopy, and colonoscopy) among Chinese older adults. A total of 114 community-dwelling older adults were asked to look at the corresponding promotional materials (pamphlet, cartoon, and video) of one of the three study groups. The pamphlet and video represent convention strategies and the cartoon represents an innovative strategy. No significant difference was observed in the screening interest and cancer fear across groups. FOBT was the most preferred screening modality. The video group has a large proportion agreed screening effectiveness of flexible sigmoidoscopy than pamphlet and cartoon groups and trusted in the screening results for FOBT and flexible sigmoidoscopy than the pamphlet group. Logistic regression results showed that the effect of trust in the screening results on screening interest for colonoscopy was greater among participants with higher cancer fear than those with lower cancer fear level. In conclusion, the three promotional groups had produced similar results in their attitudes toward CRC screening and cancer fear. The use of cartoons may be a comparable approach with conventional methods in the promotion of CRC screening. Additional components that can arouse fear and boost response efficacy

  17. Chemopreventive Strategies for Inflammation-Related Carcinogenesis: Current Status and Future Direction.

    Science.gov (United States)

    Kanda, Yusuke; Osaki, Mitsuhiko; Okada, Futoshi

    2017-04-19

    A sustained and chronically-inflamed environment is characterized by the presence of heterogeneous inflammatory cellular components, including neutrophils, macrophages, lymphocytes and fibroblasts. These infiltrated cells produce growth stimulating mediators (inflammatory cytokines and growth factors), chemotactic factors (chemokines) and genotoxic substances (reactive oxygen species and nitrogen oxide) and induce DNA damage and methylation. Therefore, chronic inflammation serves as an intrinsic niche for carcinogenesis and tumor progression. In this article, we summarize the up-to-date findings regarding definitive/possible causes and mechanisms of inflammation-related carcinogenesis derived from experimental and clinical studies. We also propose 10 strategies, as well as candidate agents for the prevention of inflammation-related carcinogenesis.

  18. Meat processing and colon carcinogenesis: cooked, nitrite-treated, and oxidized high-heme cured meat promotes mucin-depleted foci in rats

    Science.gov (United States)

    Santarelli, Raphaëlle L; Vendeuvre, Jean-Luc; Naud, Nathalie; Taché, Sylviane; Guéraud, Françoise; Viau, Michelle; Genot, Claude; Corpet, Denis E; Pierre, Fabrice H F

    2010-01-01

    Processed meat intake is associated with colorectal cancer risk, but no experimental study supports the epidemiologic evidence. To study the effect of meat processing on carcinogenesis promotion, we first did a 14-day study with 16 models of cured meat. Studied factors, in a 2 × 2 × 2 × 2 design, were muscle color (a proxy for heme level), processing temperature, added nitrite, and packaging. Fischer 344 rats were fed these 16 diets, and we evaluated fecal and urinary fat oxidation and cytotoxicity, three biomarkers of heme-induced carcinogenesis promotion. A principal component analysis allowed for selection of four cured meats for inclusion into a promotion study. These selected diets were given for 100 days to rats pretreated with 1,2-dimethylhydrazine. Colons were scored for preneoplastic lesions: aberrant crypt foci (ACF) and mucin-depleted foci (MDF). Cured meat diets significantly increased the number of ACF/colon compared with a no-meat control diet (P = 0.002). Only the cooked nitrite-treated and oxidized high heme meat significantly increased the fecal level of apparent total N-nitroso compounds (ATNC) and the number of MDF per colon compared with the no-meat control diet (P meat specifically increased the MDF number compared with similar non nitrite-treated meat (P = 0.03) and with similar non oxidized meat (P = 0.004). Thus, a model cured meat, similar to ham stored aerobically, increased the number of preneoplastic lesions, which suggests colon carcinogenesis promotion. Nitrite treatment and oxidation increased this promoting effect, which was linked with increased fecal ATNC level. This study could lead to process modifications to make non promoting processed meat. PMID:20530708

  19. Dietary B vitamin and methionine intake and MTHFR C677T genotype on risk of colorectal tumors in Lynch syndrome : the GEOLynch cohort study

    NARCIS (Netherlands)

    Jung, Audrey Y.; van Duijnhoven, Franzel J. B.; Nagengast, Fokko M.; Botma, Akke; Heine-Broring, Renate C.; Kleibeuker, Jan H.; Vasen, Hans F. A.; Harryvan, Jan L.; Winkels, Renate M.; Kampman, Ellen

    Dietary intake of B vitamins and methionine, essential components of DNA synthesis and methylation pathways, may influence colorectal tumor (CRT) development. The impact of B vitamins on colorectal carcinogenesis in individuals with Lynch syndrome (LS) is unknown but is important given their high

  20. Dietary B vitamin and methionine intake and MTHFR C677T genotype on risk of colorectal tumors in Lynch syndrome: the GEOLynch cohort study

    NARCIS (Netherlands)

    Jung, A.Y.; Duijnhoven, van F.J.B.; Nagengast, F.M.; Botma, A.; Heine-Bröring, R.C.; Kleibeuker, J.H.; Vasen, H.F.A.; Harryvan, J.L.; Winkels, R.M.; Kampman, E.

    2014-01-01

    Purpose Dietary intake of B vitamins and methionine, essential components of DNA synthesis and methylation pathways, may influence colorectal tumor (CRT) development. The impact of B vitamins on colorectal carcinogenesis in individuals with Lynch syndrome (LS) is unknown but is important given their

  1. Sucrose enhancement of the early steps of colon carcinogenesis in mice.

    Science.gov (United States)

    Stamp, D; Zhang, X M; Medline, A; Bruce, W R; Archer, M C

    1993-04-01

    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.

  2. Liver Development, Regeneration, and Carcinogenesis

    Directory of Open Access Journals (Sweden)

    Janet W. C. Kung

    2010-01-01

    Full Text Available The identification of putative liver stem cells has brought closer the previously separate fields of liver development, regeneration, and carcinogenesis. Significant overlaps in the regulation of these processes are now being described. For example, studies in embryonic liver development have already provided the basis for directed differentiation of human embryonic stem cells and induced pluripotent stem cells into hepatocyte-like cells. As a result, the understanding of the cell biology of proliferation and differentiation in the liver has been improved. This knowledge can be used to improve the function of hepatocyte-like cells for drug testing, bioartificial livers, and transplantation. In parallel, the mechanisms regulating cancer cell biology are now clearer, providing fertile soil for novel therapeutic approaches. Recognition of the relationships between development, regeneration, and carcinogenesis, and the increasing evidence for the role of stem cells in all of these areas, has sparked fresh enthusiasm in understanding the underlying molecular mechanisms and has led to new targeted therapies for liver cirrhosis and primary liver cancers.

  3. Colorectal Cancer

    African Journals Online (AJOL)

    Peter Donald

    history, young age at onset and presence of other specific tumours and defects. Among these defects are ... medical advice. Only 2 (6.3%) patients completed their treatment regimen. Conclusion: The incidence of colorectal cancer is still low in our environment but treatment outcome remains poor due to late presentation.

  4. Gut Microbe-Mediated Suppression of Inflammation-Associated Colon Carcinogenesis by Luminal Histamine Production.

    Science.gov (United States)

    Gao, Chunxu; Ganesh, Bhanu Priya; Shi, Zhongcheng; Shah, Rajesh Rasik; Fultz, Robert; Major, Angela; Venable, Susan; Lugo, Monica; Hoch, Kathleen; Chen, Xiaowei; Haag, Anthony; Wang, Timothy C; Versalovic, James

    2017-10-01

    Microbiome-mediated suppression of carcinogenesis may open new avenues for identification of therapeutic targets and prevention strategies in oncology. Histidine decarboxylase (HDC) deficiency has been shown to promote inflammation-associated colorectal cancer by accumulation of CD11b+Gr-1+ immature myeloid cells, indicating a potential antitumorigenic effect of histamine. Here, we demonstrate that administration of hdc+Lactobacillus reuteri in the gut resulted in luminal hdc gene expression and histamine production in the intestines of Hdc-/- mice. This histamine-producing probiotic decreased the number and size of colon tumors and colonic uptake of [18F]-fluorodeoxyglucose by positron emission tomography in Hdc-/- mice. Administration of L. reuteri suppressed keratinocyte chemoattractant (KC), Il22, Il6, Tnf, and IL1α gene expression in the colonic mucosa and reduced the amounts of proinflammatory, cancer-associated cytokines, keratinocyte chemoattractant, IL-22, and IL-6, in plasma. Histamine-generating L. reuteri also decreased the relative numbers of splenic CD11b+Gr-1+ immature myeloid cells. Furthermore, an isogenic HDC-deficient L. reuteri mutant that was unable to generate histamine did not suppress carcinogenesis, indicating a significant role of the cometabolite, histamine, in suppression of chronic intestinal inflammation and colorectal tumorigenesis. These findings link luminal conversion of amino acids to biogenic amines by gut microbes and probiotic-mediated suppression of colorectal neoplasia. Copyright © 2017 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  5. Diagnosing lynch syndrome in absence of colorectal cancer.

    Science.gov (United States)

    Lynch, Henry T; Knezetic, Joseph; Lanspa, Stephen

    2012-11-01

    There are many ways in which a diagnosis of Lynch syndrome can be made, most prominent of which is family history, presence of cancer, high microsatellite instability, immunohistochemistry, and a mismatch repair germline mutation. There are at least four molecular pathways for colorectal cancer carcinogenesis: 1) adenoma-carcinoma sequence; 2) hereditary microsatellite instability; 3) serrated pathway; 4) epidermal growth factor receptor. The answer to diagnosing Lynch syndrome in the absence of colorectal cancer may be partially based upon the phenotypic characteristics of the colonic polyps should they be identified at colonoscopy, specifically their phenotypic characteristics of location, size, histology, number, and age of polyp onset.

  6. Selenium in human mammary carcinogenesis

    DEFF Research Database (Denmark)

    Overvad, Kim; Grøn, P.; Langhoff, Otto

    1991-01-01

    In a case-referent study on the possible role of selenium in human mammary carcinogenesis, serum selenium was found to be 79 +/- 12 micrograms/l in 66 cases and 81 +/- 12 micrograms/l in 93 referents. An internal trend in serum selenium was observed among cases (TNM stage I 81 +/- 11 micrograms....../l and TNM stage II 76 +/- 13 micrograms selenium/l), indicating disease-mediated changes. The evaluation of selenium as a risk indicator in human breast cancer was therefore restricted to TNM stage I patients (n = 36). Multiple logistic regression analyses including variables associated with selenium levels...... revealed no association between selenium levels and breast cancer risk....

  7. Genetic factors for breast carcinogenesis

    Directory of Open Access Journals (Sweden)

    Pedro Enrique Miguel-Soca

    2016-12-01

    Full Text Available Breast cancer is a multifactorial genenetic disease in which oncogenes derived from normal cellular genes intervene, which constitute positive signals of cellular proliferation and tumour suppressor genes and represent negative signals of cells multiplication and differentiation. Although these alterations which affect germinal cells produce inherited cancers, in most of the cases somatic cell genes are affected. To the susceptibility of cancer due to genes as BRCA1 and BCRA2, the effect of factors associated to environment, life style and toxic habits are added, these determine a complex interrelation genes-environment which imply an activation of oncogenes and inactivation of tumour suppressors. The objective of this review in to offer an updated view about the main genes implied in breast carcinogenesis. The topic is controversial y currently deeply investigated.

  8. Colorectal cancers with microsatellite instability display unique miRNA profiles

    Science.gov (United States)

    Balaguer, Francesc; Moreira, Leticia; Lozano, Jose Juan; Link, Alexander; Ramirez, Georgina; Shen, Yan; Cuatrecasas, Miriam; Arnold, Mildred; Meltzer, Stephen J.; Syngal, Sapna; Stoffel, Elena; Jover, Rodrigo; Llor, Xavier; Castells, Antoni; Boland, C. Richard; Gironella, Meritxell; Goel, Ajay

    2011-01-01

    Purpose microRNAs (miRNAs) are small non-coding transcripts that play an important role in carcinogenesis. miRNA expression profiles have been shown to discriminate between different types of cancers. The aim of this study was to analyze the global miRNA signatures in various groups of colorectal cancers (CRCs) based on the presence of microsatellite instability (MSI). Experimental Design We analyzed genome-wide miRNA expression profiles in 54 CRCs (22 with Lynch syndrome, 13 sporadic MSI due to MLH1 methylation, 19 without MSI [MSS]) and 20 normal colonic tissues by miRNA microarrays. Using an independent set of MSI samples (13 with Lynch syndrome and 20 with sporadic MSI) we developed a miRNA-based predictor to differentiate both types of MSI by quantitative reverse transcriptase PCR. Results We found that the expression of a subset of 9 miRNAs significantly discriminates between tumor and normal colonic mucosa (overall error rate (OER) =0.04). More importantly, Lynch syndrome tumors displayed a unique miRNA profile compared with sporadic MSI tumors; miR-622, miR-1238 and miR-192* were the most differentially expressed miRNAs between these two groups. We developed a miRNA-based predictor able to differentiate the type of MSI in an independent set of samples. Conclusions CRC tissues show distinct miRNA expression profiles compared to normal colonic mucosa. The discovery of unique miRNA expression profiles that can successfully discriminate between Lynch syndrome, sporadic MSI and sporadic MSS CRCs provides novel insights into the role of miRNAs in colorectal carcinogenesis which may contribute to the diagnosis, prognosis and treatment of this disease. PMID:21844009

  9. Clinical and Biological Features of Interval Colorectal Cancer

    OpenAIRE

    Lee, Yu Mi; Huh, Kyu Chan

    2017-01-01

    Interval colorectal cancer (I-CRC) is defined as a CRC diagnosed within 60 months after a negative colonoscopy, taking into account that 5 years is the ?mean sojourn time.? It is important to prevent the development of interval cancer. The development of interval colon cancer is associated with female sex, old age, family history of CRC, comorbidities, diverticulosis, and the skill of the endoscopist. During carcinogenesis, sessile serrated adenomas/polyps (SSA/Ps) share many genomic and colo...

  10. Fusobacterium nucleatum Promotes Chemoresistance to Colorectal Cancer by Modulating Autophagy.

    Science.gov (United States)

    Yu, TaChung; Guo, Fangfang; Yu, Yanan; Sun, Tiantian; Ma, Dan; Han, Jixuan; Qian, Yun; Kryczek, Ilona; Sun, Danfeng; Nagarsheth, Nisha; Chen, Yingxuan; Chen, Haoyan; Hong, Jie; Zou, Weiping; Fang, Jing-Yuan

    2017-07-27

    Gut microbiota are linked to chronic inflammation and carcinogenesis. Chemotherapy failure is the major cause of recurrence and poor prognosis in colorectal cancer patients. Here, we investigated the contribution of gut microbiota to chemoresistance in patients with colorectal cancer. We found that Fusobacterium (F.) nucleatum was abundant in colorectal cancer tissues in patients with recurrence post chemotherapy, and was associated with patient clinicopathological characterisitcs. Furthermore, our bioinformatic and functional studies demonstrated that F. nucleatum promoted colorectal cancer resistance to chemotherapy. Mechanistically, F. nucleatum targeted TLR4 and MYD88 innate immune signaling and specific microRNAs to activate the autophagy pathway and alter colorectal cancer chemotherapeutic response. Thus, F. nucleatum orchestrates a molecular network of the Toll-like receptor, microRNAs, and autophagy to clinically, biologically, and mechanistically control colorectal cancer chemoresistance. Measuring and targeting F. nucleatum and its associated pathway will yield valuable insight into clinical management and may ameliorate colorectal cancer patient outcomes. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. A novel single-port technique for transanal rectosigmoid resection and colorectal anastomosis on an ex vivo experimental model.

    Science.gov (United States)

    Bhattacharjee, Hemanga K; Buess, Gerhard F; Becerra Garcia, Francisco Cesar; Storz, Pirmin; Sharma, Mousumi; Susanu, Sidonia; Kirschniak, Andreas; Misra, Mahesh C

    2011-06-01

    In the context of natural orifice translumenal endoscopic surgery (NOTES), we developed a new set of rigid instruments according to the principles of transanal endoscopic microsurgery (TEM).These instruments are long, curved, and steerable by rotating two wheels near its handle. Our success in transvaginal cholecystectomy in human with these instruments motivated us to explore the feasibility of rectosigmoid resection through the anus. The young bovine large bowel with attached organs is collected en bloc and reintegrated into an anatomically designed trainer to reproduce the human anatomy. The technique comprises the following: (1) closure of the rectal lumen by an endolumenal pursestring suture; (2) transection of the rectal wall 1 cm distal to the pursestring suture and continuation of the dissection toward the fascia and upward excising the mesorectal tissue; (3) inferior mesenteric artery is divided near its origin; (4) the colon is mobilized up to the splenic flexure; (5) the mobilized colon is brought down to the pelvis, ligated twice at the intended proximal resection site, and divided between the ligatures; (6) specimen is delivered transanally; and (7) intestinal continuity is restored by stapled or hand-sutured anastomosis. Twelve rectosigmoid resections, 20 stapled, and 27 hand-sutured anastomoses were performed in two experimental setups. Mean operation time for the resection part was 78.6 min (standard deviation (SD)=9.9). The average specimen length was 37.2 cm. During dissection in the pelvis, as the specimen was pushed upward and toward abdomen, an "empty pelvis" view of the working field was achieved, facilitating dissection. The mean operation time for hand-sutured and stapled anastomoses were 47.7 (SD=6.9) and 43.3 (SD=7.1) min, respectively. Both groups had one anastomotic leak. Transanal rectosigmoid resection is feasible with TEM technology. The unobstructed "empty pelvis" view is likely to enhance the quality of mesorectal dissection.

  12. One to 2-year surveillance intervals reduce risk of colorectal cancer in families with Lynch syndrome

    NARCIS (Netherlands)

    Vasen, Hans F. A.; Abdirahman, Mohamed; Brohet, Richard; Langers, Alexandra M. J.; Kleibeuker, Jan H.; van Kouwen, Mariette; Koornstra, Jan Jacob; Boot, Henk; Cats, Annemieke; Dekker, Evelien; Sanduleanu, Silvia; Poley, Jan-Werner; Hardwick, James C. H.; de Vos tot Nederveen Cappel, Wouter H.; van der Meulen-de Jong, Andrea E.; Tan, T. Gie; Jacobs, Maarten A. J. M.; Mohamed, Faig Lall A.; de Boer, Sijbrand Y.; van de Meeberg, Paul C.; Verhulst, Marie-Louise; Salemans, Jan M.; van Bentem, Nico; Westerveld, B. Dik; Vecht, Juda; Nagengast, Fokko M.

    2010-01-01

    BACKGROUND & AIMS: Two percent to 4% of all cases of colorectal cancer (CRC) are associated with Lynch syndrome. Dominant clustering of CRC (non-Lynch syndrome) accounts for 1%-3% of the cases. Because carcinogenesis is accelerated in Lynch syndrome, an intensive colonoscopic surveillance program

  13. DNA methyltransferase and alcohol dehydrogenase: gene-nutrient interactions in relation to risk of colorectal polyps.

    NARCIS (Netherlands)

    Jung, A.Y.; Poole, E.M.; Bigler, J.; Whitton, J.; Potter, J.D.; Ulrich, C.M.

    2008-01-01

    Disturbances in DNA methylation are a characteristic of colorectal carcinogenesis. Folate-mediated one-carbon metabolism is essential for providing one-carbon groups for DNA methylation via DNA methyltransferases (DNMTs). Alcohol, a folate antagonist, could adversely affect one-carbon metabolism. In

  14. Red and Processed Meat and Colorectal Cancer Incidence: Meta-Analysis of Prospective Studies

    NARCIS (Netherlands)

    Chan, D.S.M.; Lau, R.; Aune, D.; Vieira, R.; Greenwood, D.C.; Kampman, E.; Norat, T.

    2011-01-01

    Background: The evidence that red and processed meat influences colorectal carcinogenesis was judged convincing in the 2007 World Cancer Research Fund/American Institute of Cancer Research report. Since then, ten prospective studies have published new results. Here we update the evidence from

  15. Red and processed meat and colorectal cancer incidence: meta-analysis of prospective studies

    NARCIS (Netherlands)

    Chan, D.S.; Lau, R.; Aune, D.; Vieira, R.; Greenwood, D.C.; Kampman, E.; Norat, T.

    2011-01-01

    BACKGROUND: The evidence that red and processed meat influences colorectal carcinogenesis was judged convincing in the 2007 World Cancer Research Fund/American Institute of Cancer Research report. Since then, ten prospective studies have published new results. Here we update the evidence from

  16. COX-2 inhibition as a tool to treat and prevent colorectal cancer

    NARCIS (Netherlands)

    Tuynman, J. B.; Peppelenbosch, M. P.; Richel, D. J.

    2004-01-01

    The cyclooxygenase-2 (COX-2) enzyme has a fundamental role in the carcinogenesis of colorectal cancer. The anticarcinogenic mechanisms of NSAIDs are not completely understood and appear to be only partially dependent on inhibition tumoral COX-2. Moreover, the mechanisms of NSAIDs depend on the

  17. Prognostic significance of COX-2 and β-catenin in colorectal carcinoma

    Directory of Open Access Journals (Sweden)

    Amani Kazem

    2014-09-01

    Conclusion: Both β-catenin and COX-2 expression may play an important role in the evolution of colon carcinogenesis. Increased expression of both could be used as a marker of tumor progression and poor prognosis. This might be of therapeutic value for allocating patients with colorectal carcinoma to different treatment modalities.

  18. Emerging roles of lactic acid bacteria in protection against colorectal cancer.

    Science.gov (United States)

    Zhong, Li; Zhang, Xufei; Covasa, Mihai

    2014-06-28

    Colorectal cancer (CRC) is the third leading cause of cancer deaths worldwide and the fourth most common cancer diagnosed among men and women in the United States. Considering the risk factors of CRC, dietary therapy has become one of the most effective approaches in reducing CRC morbidity and mortality. The use of probiotics is increasing in popularity for both the prevention and treatment of a variety of diseases. As the most common types of microbes used as probiotics, lactic acid bacteria (LAB) are comprised of an ecologically diverse group of microorganisms united by formation of lactic acid as the primary metabolite of sugar metabolism. LAB have been successfully used in managing diarrhea, food allergies, and inflammatory bowel disease. LAB also demonstrated a host of properties in preventing colorectal cancer development by inhibiting initiation or progression through multiple pathways. In this review, we discuss recent insights into cellular and molecular mechanisms of LAB in CRC prevention including apoptosis, antioxidant DNA damages, immune responses, and epigenetics. The emerging experimental findings from clinical trials as well as the proposed mechanisms of gut microbiota in carcinogenesis will also be briefly discussed.

  19. Protein expression analysis of inflammation-related colon carcinogenesis

    Directory of Open Access Journals (Sweden)

    Yasui Yumiko

    2009-01-01

    Full Text Available Background: Chronic inflammation is a risk factor for colorectal cancer (CRC development. The aim of this study was to determine the differences in protein expression between CRC and the surrounding nontumorous colonic tissues in the mice that received azoxymethane (AOM and dextran sodium sulfate (DSS using a proteomic analysis. Materials and Methods: Male ICR mice were given a single intraperitoneal injection of AOM (10 mg/kg body weight, followed by 2% (w/v DSS in their drinking water for seven days, starting one week after the AOM injection. Colonic adenocarcinoma developed after 20 weeks and a proteomics analysis based on two-dimensional gel electrophoresis and ultraflex TOF/TOF mass spectrometry was conducted in the cancerous and nontumorous tissue specimens. Results: The proteomic analysis revealed 21 differentially expressed proteins in the cancerous tissues in comparison to the nontumorous tissues. There were five markedly increased proteins (beta-tropomyosin, tropomyosin 1 alpha isoform b, S100 calcium binding protein A9, and an unknown protein and 16 markedly decreased proteins (Car1 proteins, selenium-binding protein 1, HMG-CoA synthase, thioredoxin 1, 1 Cys peroxiredoxin protein 2, Fcgbp protein, Cytochrome c oxidase, subunit Va, ETHE1 protein, and 7 unknown proteins. Conclusions: There were 21 differentially expressed proteins in the cancerous tissues of the mice that received AOM and DSS. Their functions include metabolism, the antioxidant system, oxidative stress, mucin production, and inflammation. These findings may provide new insights into the mechanisms of inflammation-related colon carcinogenesis and the establishment of novel therapies and preventative strategies to treat carcinogenesis in the inflamed colon.

  20. Recent progress in nickel carcinogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Sunderman, F.W. Jr.

    1984-01-01

    Positive bacterial mutagenesis tests have been obtained with Ni(II) in Corynybacterium, but not in E. coli, S. typhimurium, or B. subtilis. Transformation assays of several soluble and crystalline Ni compounds have been positive in Syrian hamster embryo cells. Ni(II) binds to DNA, RNA, and nucleoproteins, and becomes localized in nucleoli. Genotoxic effects of Ni include: (a) chromosomal aberrations, including sister-chromatid exchanges, (b) DNA strandbreaks and DNA-protein crosslinks, (c) inhibition of DNA and RNA synthesis, (d) infidelity of DNA transcription, and (e) mutations at the HGPRTase locus in Chinese hamster cells and the TK locus in mouse lymphoma cells. These findings are consistent with somatic mutation as the mechanism for initiation of nickel carcinogenesis. Ni compounds cause reversible transition of double-stranded poly(dG-dC) DNA from the right-handed B-helix to the left-handed Z-helix, suggesting a mechanism whereby nickel might modulate oncogene expression. 99 references, 4 tables.

  1. The role of selected matrix metalloproteinases and their inhibitors in colorectal cancer developme

    Directory of Open Access Journals (Sweden)

    Magdalena Groblewska

    2010-01-01

    Full Text Available Colorectal cancer is one of the most common malignant tumors of the gastrointestinal tract. The development of this tumor is a complex, long-term, and multi-step process, from small dysplastic lesions of normal colorectal mucosa, through adenomatous polyps, to carcinoma in situ. Matrix metalloproteinases (MMPs and their tissue inhibitors (TIMPs play an important role in colorectal carcinogenesis. MMP-9 is able to degrade collagen IV from basement membranes and extracellular matrix, which is associated with tumor progression, including invasion, metastasis, growth, migration, and angiogenesis. It was demonstrated that increased expression of MMP-9 plays a crucial role in the development of several human malignancies, including colorectal cancer. Increased expression of MMP-9 correlated with tumor stage, invasiveness, and poor survival of colorectal cancer patients.

  2. O modelo experimental de carcinogênese gástrica induzido por n-methyl-n-nitrosourea em ratos F344 e camundongos C3H é válido para os ratos Wistar? Experimental model of gastric carcinogenesis with N-methyl-N-nitrosourea for F344 rats and C3H mices is valid for Wistar rats?

    Directory of Open Access Journals (Sweden)

    Lissandro Tarso

    2011-03-01

    were killed until 70 weeks. RESULTS: Survival rate was higher than 90%. It had the induction of two adenocarcinomas, one squamous cell carcinoma and one sarcoma. The incidence of gastric adenocarcinoma was 4.5% (0.5 to 15. CONCLUSIONS: The experimental model of gastric carcinogenesis in Wistar rats, using MNU dissolved in water, showed not practice viability in this study due to the low rate of gastric adenocarcinoma.

  3. Role of bacteria in oral carcinogenesis

    Directory of Open Access Journals (Sweden)

    R Rajeev

    2012-01-01

    Full Text Available Oral cancer is the most common cancer diagnosed in Indian men and is the leading cause of cancer deaths. It is considered as a multistep and multifactorial disease. Besides accumulation of genetic mutations, numerous other carcinogens are involved. In this category, viral and chemical carcinogens are well studied and documented. However, in the oral cavity, the role of microbiota in carcinogenesis is not known. Microbial populations on mouth mucosa differ between healthy and malignant sites, and certain oral bacterial species have been linked with malignancies, but the evidence is still weak in this respect. Nevertheless, oral microorganisms inevitably up-regulate cytokines and other inflammatory mediators that affect the complex metabolic pathways, and may thus be involved in carcinogenesis. Poor oral health associates statistically with prevalence of many types of cancer such as pancreatic and gastrointestinal cancer. This review presents possible carcinogenesis pathway involved in bacterial carcinogenesis, commonly implicated bacteria in oral carcinogenesis, and their role in cancer therapeutics as well.

  4. Metals distribution in colorectal biopsies: New insight on the elemental fingerprint of tumour tissue.

    Science.gov (United States)

    Rinaldi, Leslie; Barabino, Gabriele; Klein, Jean-Philippe; Bitounis, Dimitrios; Pourchez, Jérémie; Forest, Valérie; Boudard, Delphine; Leclerc, Lara; Sarry, Gwendoline; Roblin, Xavier; Cottier, Michèle; Phelip, Jean-Marc

    2015-07-01

    Some studies have linked colorectal cancer to metal exposure. Our objective was to evaluate the element distribution in colorectal adenocarcinoma biopsies, adjacent non-tumour tissues, and healthy controls. The study is a case-control study which compared the element distribution in colon biopsies from two groups of patients: with colorectal cancer (2 types of samples: colorectal cancer biopsies and adjacent non-tumour tissues) and healthy controls. Fifteen metal concentrations (Aluminium, Boron, Cadmium, Chromium, Copper, Iron, Magnesium, Manganese, Nickel, Lead, Selenium, Silicon, Titanium, Vanadium, and Zinc) were quantified by using inductively coupled plasma atomic emission spectrometry. 104 patients were included: 76 in the colorectal cancer group, 28 in the healthy control group. Among the 15 elements analyzed, only boron, chromium, zinc, silicon and magnesium were found at clearly detectable concentrations. Colorectal tumour biopsies had significantly higher concentrations of magnesium as compared to adjacent non-tumour or healthy tissues. Zinc concentration followed the same trend but differences were not statistically significant. In addition, concentration of silicon was higher in colorectal cancer tissue than in healthy non-cancer tissue, while chromium was mostly found in adjacent non-tumour tissue. Magnesium, chromium, zinc and silicon were found in noteworthy concentrations in colorectal tumour. Their potential role in colorectal carcinogenesis should be explored. Copyright © 2015 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

  5. Bacterionomics and vironomics in carcinogenesis

    Directory of Open Access Journals (Sweden)

    Pratiwi Sudarmono

    2017-02-01

    Full Text Available Virus and bacteria are microbes which are very common cause human infection. Most of the bacterial infection can be eradicated by antibiotics and infection symptoms disappear. But for virus infection, once infected, the virus will persistently stay in the host, even undergo not only a lytic cycle but also integrated into host genome. Nowadays, at least 6 virus type are consistently related to human cancer, such as EBV,HPV,HTLV,HBV,HCV,HKSV, and the new one Merkel Virus (MCV. Although not every infected people will get cancer, but around 20% of the whole cancer in human are caused by viral oncogene. Class one oncogenic bacterial is Helicobacter pylori. Infection with this bacteria can cause persistent gastro duodenal inflammation which cause some alteration in gastric cell growth into transformation. Expression of Cag gene and Vac gene and some expression of OMP protein usually link to gastric cancer. Molecular mechanisms of carcinogenesis for every virus which cause infection  is a very complex , which include several processes caused by cell transformation. Besides, other host and environmental factors are also play a significant role in cancer development. Some scientist put a Hallmark analysis as a model to quickly summarize what pathobiology process will happen and what gene or protein caused the process. The Hallmark analysis comprise of several process which may happen simultaneously because some of the Hallmark is caused by the same protein. The Hallmark consists of various virus strategies in oncogenesis such as promoting angiogenesis, avoiding immune destruction, genome instability and mutation, deregulating cellular energetic, resisting cell death, sustaining proliferative signaling, evading growth suppressors, enabling cellular immortality, promoting inflammation and activation metastasis. For example, infection by HPV, will cause low grade dysplasia which can continue to invasive cervical cancer. After host cell transformation, in

  6. Modeling Multiple Causes of Carcinogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Jones, T D

    1999-01-24

    multiple causes of carcinogenesis and shifts the risk-assessment logic to considerations of "what dose does?" in contrast to the current process of the substance-specific question of "what dose is?" Whether reactive oxygen is the proximate or contributing cause of disease or simply a better estimate of biologically effective dose, it has enormous advantages for improved risk- and policy-based decisions. Various estimates of immune system modulation will be given based on radiobiology.

  7. BRAFV600E: implications for carcinogenesis and molecular therapy.

    LENUS (Irish Health Repository)

    Cantwell-Dorris, Emma R

    2012-02-01

    The mitogen-activated protein kinase (MAPK)\\/extracellular signal-regulated kinase (ERK) pathway is frequently mutated in human cancer. This pathway consists of a small GTP protein of the RAS family that is activated in response to extracellular signaling to recruit a member of the RAF kinase family to the cell membrane. Active RAF signals through MAP\\/ERK kinase to activate ERK and its downstream effectors to regulate a wide range of biological activities including cell differentiation, proliferation, senescence, and survival. Mutations in the v-raf murine sarcoma viral oncogenes homolog B1 (BRAF) isoform of the RAF kinase or KRAS isoform of the RAS protein are found as activating mutations in approximately 30% of all human cancers. The BRAF pathway has become a target of interest for molecular therapy, with promising results emerging from clinical trials. Here, the role of the most common BRAF mutation BRAF(V600E) in human carcinogenesis is investigated through a review of the literature, with specific focus on its role in melanoma, colorectal, and thyroid cancers and its potential as a therapeutic target.

  8. Oxidative stress and inflammation in liver carcinogenesis

    Directory of Open Access Journals (Sweden)

    Natalia Olaya

    2007-02-01

    series of transcription factors. Moreover, in addition to direct production of ROS by these pathogens, liver infiltration by activated phagocytic cells provides an additional source of ROS production that promotes oxidative stress via interleukin or NO production that can damage proteins, lipids and DNA.

    Nuclear MSI was demonstrated first in familial hereditary colorectal cancer (HNPCC and then in sporadic cancers, primarily digestive tract cancers such as colorectal, gastric and pancreatic cancers.In HCC, although nuclear MSI has been shown in some studies (15,18, there is as yet no direct evidence of alteration of the MMR genes and the biological and the clinicopathological significance of the lowlevel MSI seen in HCC is unclear. MSI has also been shown to occur in inflammatory tissues such as chronic hepatitis and cirrhosis as well as in ulcerative colitis, chronic pancreatitis and in non digestive inflammatory diseases such as rheumatoid arthritis.

    Recently, the role of mitochondria in carcinogenesis has been under numerous investigation, in part because their prominent role in apoptosis, ROS production and other aspects of tumour biology. The mitochondrial genome is particularly susceptible to mutations because of the high level of ROS generation in this organelle, coupled with a relatively low level of DNA repair. Somatic mutations of mitochondrial DNA (mtDNA have been shown in HCC as was also observed MSI. These findings suggest a potential role for mitochondrial genome instability in the early steps of tumorigenesis.

    Ischemia-reperfusion injury can occur in several situations and is a major cause of cell damage during surgery. Cells and tissues subjected to hypoxia by prolonged ischemia become acidic

  9. Understanding Carcinogenesis for Fighting Oral Cancer

    Directory of Open Access Journals (Sweden)

    Takuji Tanaka

    2011-01-01

    Full Text Available Oral cancer is one of the major global threats to public health. Oral cancer development is a tobacco-related multistep and multifocal process involving field cancerization and carcinogenesis. The rationale for molecular-targeted prevention of oral cancer is promising. Biomarkers of genomic instability, including aneuploidy and allelic imbalance, are able to measure the cancer risk of oral premalignancies. Understanding of the biology of oral carcinogenesis will give us important advances for detecting high-risk patients, monitoring preventive interventions, assessing cancer risk, and pharmacogenomics. In addition, novel chemopreventive agents based on molecular mechanisms and targets against oral cancers will be derived from research using appropriate animal carcinogenesis models. New approaches, such as interventions with molecular-targeted agents and agent combinations in high-risk oral individuals, are undoubtedly needed to reduce the devastating worldwide consequences of oral malignancy.

  10. High Prevalence of Human Papillomavirus in Colorectal Cancer in Hispanics: A Case-Control Study

    Directory of Open Access Journals (Sweden)

    Raul D. Bernabe-Dones

    2016-01-01

    Full Text Available The role of Human Papillomavirus (HPV in colorectal carcinogenesis remains elusive. Based on the high incidence of HPV-associated malignancies among Puerto Rican Hispanics, this study aimed to assess the prevalence of HPV infection and viral integration in colorectal tissues in order to evaluate its putative role in colorectal cancer (CRC. In this case-control study, the prevalence of HPV infection in CRC (cases n = 45 and normal colon mucosa from cancer-free subjects (controls n = 36 was assessed by a nested PCR strategy. HPV-16 genotyping was performed in HPV-positive tissues and the physical status of the HPV-16 genome was determined by E2 detection. HPV was detected in 19 of 45 (42.2% CRC cases (mean age 61.1 ± 10.7 years, 24 males and in 1 of 36 (2.8% controls (mean age 60.9 ± 9.6 years, 24 males with an OR = 25.58 (95% CI 3.21 to 203.49. HPV-16 was detected in 63.2% of the HPV-positive colorectal tumors; genome integration was observed in all HPV-16 positive cases. This is the first report showing the high prevalence of HPV infections in Caribbean Hispanic colorectal tumors. Despite evidence of HPV integration into the host genome, further mechanistic analysis examining HPV oncoprotein expression and the putative role of these oncoproteins in colorectal carcinogenesis is warranted.

  11. Light/Dark Shifting Promotes Alcohol-Induced Colon Carcinogenesis: Possible Role of Intestinal Inflammatory Milieu and Microbiota.

    Science.gov (United States)

    Bishehsari, Faraz; Saadalla, Abdulrahman; Khazaie, Khashayarsha; Engen, Phillip A; Voigt, Robin M; Shetuni, Brandon B; Forsyth, Christopher; Shaikh, Maliha; Vitaterna, Martha Hotz; Turek, Fred; Keshavarzian, Ali

    2016-12-02

    Colorectal cancer (CRC) is associated with the modern lifestyle. Chronic alcohol consumption-a frequent habit of majority of modern societies-increases the risk of CRC. Our group showed that chronic alcohol consumption increases polyposis in a mouse mode of CRC. Here we assess the effect of circadian disruption-another modern life style habit-in promoting alcohol-associated CRC. TS4Cre × adenomatous polyposis coli (APC)lox468 mice underwent (a) an alcohol-containing diet while maintained on a normal 12 h light:12 h dark cycle; or (b) an alcohol-containing diet in conjunction with circadian disruption by once-weekly 12 h phase reversals of the light:dark (LD) cycle. Mice were sacrificed after eight weeks of full alcohol and/or LD shift to collect intestine samples. Tumor number, size, and histologic grades were compared between animal groups. Mast cell protease 2 (MCP2) and 6 (MCP6) histology score were analyzed and compared. Stool collected at baseline and after four weeks of experimental manipulations was used for microbiota analysis. The combination of alcohol and LD shifting accelerated intestinal polyposis, with a significant increase in polyp size, and caused advanced neoplasia. Consistent with a pathogenic role of stromal tryptase-positive mast cells in colon carcinogenesis, the ratio of mMCP6 (stromal)/mMCP2 (intraepithelial) mast cells increased upon LD shifting. Baseline microbiota was similar between groups, and experimental manipulations resulted in a significant difference in the microbiota composition between groups. Circadian disruption by Light:dark shifting exacerbates alcohol-induced polyposis and CRC. Effect of circadian disruption could, at least partly, be mediated by promoting a pro-tumorigenic inflammatory milieu via changes in microbiota.

  12. Light/Dark Shifting Promotes Alcohol-Induced Colon Carcinogenesis: Possible Role of Intestinal Inflammatory Milieu and Microbiota

    Directory of Open Access Journals (Sweden)

    Faraz Bishehsari

    2016-12-01

    Full Text Available Background: Colorectal cancer (CRC is associated with the modern lifestyle. Chronic alcohol consumption—a frequent habit of majority of modern societies—increases the risk of CRC. Our group showed that chronic alcohol consumption increases polyposis in a mouse mode of CRC. Here we assess the effect of circadian disruption—another modern life style habit—in promoting alcohol-associated CRC. Method: TS4Cre × adenomatous polyposis coli (APClox468 mice underwent (a an alcohol-containing diet while maintained on a normal 12 h light:12 h dark cycle; or (b an alcohol-containing diet in conjunction with circadian disruption by once-weekly 12 h phase reversals of the light:dark (LD cycle. Mice were sacrificed after eight weeks of full alcohol and/or LD shift to collect intestine samples. Tumor number, size, and histologic grades were compared between animal groups. Mast cell protease 2 (MCP2 and 6 (MCP6 histology score were analyzed and compared. Stool collected at baseline and after four weeks of experimental manipulations was used for microbiota analysis. Results: The combination of alcohol and LD shifting accelerated intestinal polyposis, with a significant increase in polyp size, and caused advanced neoplasia. Consistent with a pathogenic role of stromal tryptase-positive mast cells in colon carcinogenesis, the ratio of mMCP6 (stromal/mMCP2 (intraepithelial mast cells increased upon LD shifting. Baseline microbiota was similar between groups, and experimental manipulations resulted in a significant difference in the microbiota composition between groups. Conclusions: Circadian disruption by Light:dark shifting exacerbates alcohol-induced polyposis and CRC. Effect of circadian disruption could, at least partly, be mediated by promoting a pro-tumorigenic inflammatory milieu via changes in microbiota.

  13. Colorectal Cancer Prevention

    Science.gov (United States)

    ... cancer: Age Family history of colorectal cancer Personal history Inherited risk Alcohol Cigarette smoking Obesity The following protective factors decrease the risk of colorectal cancer: Physical activity Aspirin Combination hormone replacement therapy Polyp removal It is ...

  14. Chemopreventive Strategies for Inflammation-Related Carcinogenesis: Current Status and Future Direction

    Science.gov (United States)

    Kanda, Yusuke; Osaki, Mitsuhiko; Okada, Futoshi

    2017-01-01

    A sustained and chronically-inflamed environment is characterized by the presence of heterogeneous inflammatory cellular components, including neutrophils, macrophages, lymphocytes and fibroblasts. These infiltrated cells produce growth stimulating mediators (inflammatory cytokines and growth factors), chemotactic factors (chemokines) and genotoxic substances (reactive oxygen species and nitrogen oxide) and induce DNA damage and methylation. Therefore, chronic inflammation serves as an intrinsic niche for carcinogenesis and tumor progression. In this article, we summarize the up-to-date findings regarding definitive/possible causes and mechanisms of inflammation-related carcinogenesis derived from experimental and clinical studies. We also propose 10 strategies, as well as candidate agents for the prevention of inflammation-related carcinogenesis. PMID:28422073

  15. MicroRNA-184 inhibits cell proliferation and metastasis in human colorectal cancer by directly targeting IGF-1R.

    Science.gov (United States)

    Wu, Guannan; Liu, Jiayun; Wu, Zhenfeng; Wu, Xiaoyu; Yao, Xuequan

    2017-09-01

    Colorectal cancer is currently the third most common cancer in males and the second in females worldwide. In spite of marked progress having been achieved in surgical resection, radiotherapy and chemotherapy, the prognosis for patients with colorectal cancer remains poor. Previous studies have demonstrated that the abnormal expression of microRNAs contributed to human cancer carcinogenesis and progression, suggesting miRNAs as novel therapeutic targets in colorectal cancer. The aim of the present study was to investigate the expression, functions and underlying molecular mechanisms of microRNA-184 (miR-184) in colorectal cancer. The results identified that miR-184 was significantly downregulated in colorectal cancer tissues and cell lines. In vitro functional studies demonstrated that miR-184 significantly inhibited colorectal cancer cell proliferation, migration and invasion. Notably, insulin-like growth factor 1 receptor (IGF-1R) was identified as a direct target of miR-184 in colorectal cancer. Furthermore, the functions of IGF-1R small interfering RNA were similar to those induced by miR-184 in colorectal cancer, suggesting IGF-1R as a functional target of miR-184 in colorectal cancer. The results of the present study indicated that miR-184 may be a novel therapeutic strategy regimen of targeted therapy for colorectal cancer.

  16. Effect of appendicectomy on colonic inflammation and neoplasia in experimental ulcerative colitis.

    Science.gov (United States)

    Harnoy, Y; Bouhnik, Y; Gault, N; Maggiori, L; Sulpice, L; Cazals-Hatem, D; Boudjema, K; Panis, Y; Ogier-Denis, E; Treton, X

    2016-10-01

    Ulcerative colitis (UC) promotes cancer, and can be ameliorated by early appendicectomy for appendicitis. The aim of the study was to explore the effect of appendicectomy on colitis and colonic neoplasia in an animal model of colitis and a cohort of patients with UC. Five-week old IL10/Nox1(DKO) mice with nascent colitis and 8-week-old IL10/Nox1(DKO) mice with established colitis underwent appendicectomy (for experimental appendicitis or no appendicitis) or sham laparotomy. The severity and extent of colitis was assessed by histopathological examination, and a clinical disease activity score was given. From a cohort of consecutive patients with UC who underwent colectomy, the prevalence of appendicectomy and pathological findings were collected from two institutional databases. Appendicectomy for appendicitis ameliorated experimental colitis in the mice; the effect was more pronounced in the 5-week-old animals. Appendicectomy in the no-appendicitis group was associated with an increased rate of colonic high-grade dysplasia (HGD) or cancer compared with rates in sham and appendicitis groups (13 of 20 versus 0 of 20 and 0 of 20 respectively; P neoplasia (odds ratio 16·88, 95 per cent c.i. 3·32 to 112·69). Appendicectomy for experimental appendicitis ameliorated colitis. The risk of colorectal neoplasia appeared to increase following appendicectomy without induced appendicitis in a mouse model of colitis, and in patients with UC who had undergone appendicectomy. Surgical relevance Appendicectomy for appendicitis protects against UC. In this murine model of colitis, appendicectomy for experimental appendicitis protected against colitis, but appendicectomy without appendicitis promoted colorectal carcinogenesis. In patients with ulcerative colitis who underwent colectomy, absence of the appendix (proof of previous appendicectomy) in the resection specimen was independently associated with colorectal neoplasia. Although patients with UC and a history of

  17. [Aspirin and colorectal cancer].

    Science.gov (United States)

    Grancher, Adrien; Michel, Pierre; Di Fiore, Frédéric; Sefrioui, David

    2018-02-01

    Colorectal cancer is a worldwide public health problem. Aspirin has been identified as a protective factor against the apparition of colorectal cancer. There are several mechanisms about the actions by aspirin on colorectal tumorogenesis. These are not perfectly known nowadays. On one hand, there are direct mechanisms on colorectal mucosa, on the other hand there are indirect mechanisms through platelet functions. Aspirin also plays a role by its anti-inflammatory action and the stimulation of antitumor immunity. Several studies show that long-term treatment with low-doses of aspirin decreases the incidence of adenomas and colorectal cancers. In the United States, aspirin is currently recommended for primary prevention of the risk of colorectal cancer in all patients aged 50 to 59, with a 10-year risk of cardiovascular event greater than 10 %. However, primary prevention with aspirin should not be a substitute for screening in colorectal cancer. Furthermore, aspirin seems to be beneficial when used in post-diagnosis of colorectal cancer. It could actually decrease the risk of metastasis in case of a localized colorectal cancer, and increase the survival in particular, concerning PIK3CA mutated tumors. The association of aspirin with neoadjuvant treatment of colorectal cancer by radiochimiotherapy seems to have beneficial effects. French prospective randomized study is currently being conducted to investigate postoperative aspirin in colorectal cancers with a PIK3CA mutation. Copyright © 2017 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.

  18. Potential roles of microRNAs and ROS in colorectal cancer: diagnostic biomarkers and therapeutic targets

    Science.gov (United States)

    Lin, Jingmei; Chuang, Chia-Chen; Zuo, Li

    2017-01-01

    As one of the most commonly diagnosed cancers worldwide, colorectal adenocarcinoma often occurs sporadically in individuals aged 50 or above and there is an increase among younger patients under 50. Routine screenings are recommended for this age group to improve early detection. The multifactorial etiology of colorectal cancer consists of both genetic and epigenetic factors. Recently, studies have shown that the development and progression of colorectal cancer can be attributed to aberrant expression of microRNA. Reactive oxygen species (ROS) that play a key role in cancer cell survival, can also lead to carcinogenesis and cancer exacerbations. Given the rapid accumulating knowledge in the field, an updated review regarding microRNA and ROS in colorectal cancer is necessary. An extensive literature search has been conducted in PubMed/Medline databases to review the roles of microRNAs and ROS in colorectal cancer. Unique microRNA expression in tumor tissue, peripheral blood, and fecal samples from patients with colorectal cancer is outlined. Therapeutic approaches focusing on microRNA and ROS in colorectal cancer treatment is also delineated. This review aims to summarize the newest knowledge on the pathogenesis of colorectal cancer in the hopes of discovering novel diagnostic biomarkers and therapeutic techniques. PMID:28061475

  19. Aberrant DNA methylation of WNT pathway genes in the development and progression of CIMP-negative colorectal cancer.

    Science.gov (United States)

    Galamb, Orsolya; Kalmár, Alexandra; Péterfia, Bálint; Csabai, István; Bodor, András; Ribli, Dezső; Krenács, Tibor; Patai, Árpád V; Wichmann, Barnabás; Barták, Barbara Kinga; Tóth, Kinga; Valcz, Gábor; Spisák, Sándor; Tulassay, Zsolt; Molnár, Béla

    2016-08-02

    The WNT signaling pathway has an essential role in colorectal carcinogenesis and progression, which involves a cascade of genetic and epigenetic changes. We aimed to analyze DNA methylation affecting the WNT pathway genes in colorectal carcinogenesis in promoter and gene body regions using whole methylome analysis in 9 colorectal cancer, 15 adenoma, and 6 normal tumor adjacent tissue (NAT) samples by methyl capture sequencing. Functional methylation was confirmed on 5-aza-2'-deoxycytidine-treated colorectal cancer cell line datasets. In parallel with the DNA methylation analysis, mutations of WNT pathway genes (APC, β-catenin/CTNNB1) were analyzed by 454 sequencing on GS Junior platform. Most differentially methylated CpG sites were localized in gene body regions (95% of WNT pathway genes). In the promoter regions, 33 of the 160 analyzed WNT pathway genes were differentially methylated in colorectal cancer vs. normal, including hypermethylated AXIN2, CHP1, PRICKLE1, SFRP1, SFRP2, SOX17, and hypomethylated CACYBP, CTNNB1, MYC; 44 genes in adenoma vs. NAT; and 41 genes in colorectal cancer vs. adenoma comparisons. Hypermethylation of AXIN2, DKK1, VANGL1, and WNT5A gene promoters was higher, while those of SOX17, PRICKLE1, DAAM2, and MYC was lower in colon carcinoma compared to adenoma. Inverse correlation between expression and methylation was confirmed in 23 genes, including APC, CHP1, PRICKLE1, PSEN1, and SFRP1. Differential methylation affected both canonical and noncanonical WNT pathway genes in colorectal normal-adenoma-carcinoma sequence. Aberrant DNA methylation appears already in adenomas as an early event of colorectal carcinogenesis.

  20. DCLK1 immunoreactivity in colorectal neoplasia

    Directory of Open Access Journals (Sweden)

    Bellows CF

    2012-04-01

    Full Text Available Giuseppe Gagliardi1, Monica Goswami1, Roberto Passera2, Charles F Bellows11Department of Surgery and Pathology, Tulane University, New Orleans, LA, USA; 2Division of Nuclear Medicine Azienda Ospedaliero-Universitaria San Giovanni Battista, Turin, ItalyIntroduction: Microtubule-associated doublecortin and CaM kinase-like-1 (DCLK1 is a novel candidate marker for intestinal stem cells. The aim of our study was to assess DCLK1 immunoreactivity in colorectal carcinogenesis and its correlation with prognosis.Methods: DCLK1 immunostaining was performed in colorectal tissue from 71 patients, including 18 adenomatous polyps, 40 primary adenocarcinomas, and 14 metastatic lesions. Each case was evaluated by a combined scoring method based on the intensity of staining (score 0–3 and the percentage of tissue staining positive (score 0–3. Immunoexpression for DCLK1 was considered as positive when the combined score was 2–6 and negative with a score of 0–1.Results: Overall, 14/18 (78% of polyps, 30/40 (75% of primary adenocarcinomas, and 7/14 (50% of distant metastases were positive for DCLK1. In adenomatous polyps and primary cancer there was no association between DCLK1 staining score and tumor pathology. However, after curative colorectal cancer resection, patients whose tumor had a high (≥5 combined staining score had increased cancer-specific mortality compared to patients with low (0–4 staining score (hazard ratio 5.89; 95% confidence interval: 1.22–28.47; P = 0.027.Conclusion: We found that DCLK1 is frequently expressed in colorectal neoplasia and may be associated with poor prognosis. Further studies are necessary to validate the use of DCLK1 as a prognostic marker.Keywords: DCLK1, DCAMKL-1, gastrointestinal stem cell, cancer stem cell, adenomatous polyps, liver metastasis, immunohistochemistry

  1. Dietary Chemoprevention of PhIP Induced Carcinogenesis in Male Fischer 344 Rats with Tomato and Broccoli

    OpenAIRE

    Canene-Adams, Kirstie; Sfanos, Karen S.; Liang, Chung-Tiang; Yegnasubramanian, Srinivasan; Nelson, William G.; Brayton, Cory; De Marzo, Angelo M.

    2013-01-01

    The heterocyclic amine, 2-amino-1-methyl-6-phenylimidazo[4,5-B]pyridine (PhIP), found in meats cooked at high temperatures, has been implicated in epidemiological and rodent studies for causing breast, prostate, and colorectal cancers. A previous animal study using a xenograft model has shown that whole tomato and broccoli, when eaten in combination, exhibit a marked effect on tumor reduction compared to when eaten alone. Our aim was to determine if PhIP-induced carcinogenesis can be prevente...

  2. Colorectal cancer: lifestyle and dietary factors Cáncer colorrectal: hábitos de vida y factores dietéticos

    OpenAIRE

    M. P. Corrêa Lima; Gomes-da-Silva,M.H.G.

    2005-01-01

    Introduction: Colorectal cancer is the most common tumor in the developed countries, and the number of new cases annualy is aproximately equal for men and women. Several environmental factors can interact in all steps of carcinogenesis. Lately the balance between genetic predisposition and these factors, including nutritional components and lifestyle behaviors, determines individual susceptibility to develop colorectal cancer. The aim of this study is to revise the references about lifestyle ...

  3. Role of micro-RNA in colorectal cancer screening.

    Science.gov (United States)

    Rodríguez-Montes, José Antonio; Menéndez Sánchez, Pablo

    2014-12-01

    MicroRNAs are involved in carcinogenesis through postranscriptional gene regulatory activity. These molecules are involved in various physiological and pathological functions, such as apoptosis, cell proliferation and differentiation, which indicates their functionality in carcinogenesis as tumour suppressor genes or oncogenes. Several studies have determined the presence of microRNAs in different neoplastic diseases such as colon, prostate, breast, stomach, pancreas, and lung cancer. There are promising data on the usefulness of quantifying microRNAs in different organic fluids and tissues. We have conducted a review of the determinations of microRNAs in the diagnosis of colorectal cancer. Copyright © 2014 AEC. Publicado por Elsevier España, S.L.U. All rights reserved.

  4. [Etiology of colorectal cancer and antioxidant barrier of the organism].

    Science.gov (United States)

    Klimczak, Alicja; Kubiak, Katarzyna; Cybulska, Magdalena; Kula, Agnieszka; Dziki, Łukasz; Malinowska, Katarzyna

    2010-03-01

    Colorectal cancer is a serious medical and economic problem in Poland, as the detection and results of its treatment are very low. Due to this fact, medical research is still conducted in order to find out the symptoms of this tumor and proper preventive measures. According to one hypothesis of carcinogenesis, the process of creating the tumor begins and develops when the balance between the production of reactive oxygen species (ROS) and their deactivation by the "antioxidant protective barrier of the organism" is disturbed. As a result of this theory, it has been decided to examine the plasma concentration of the dietary minerals which work as antioxidants. The results entailed conclusions which prove the free radicals theory of carcinogenesis. They also confirm the part which the antioxidant protective barrier plays in the defence against ROS and their carcinogenic consequences.

  5. GSTT2 promoter polymorphisms and colorectal cancer risk

    Directory of Open Access Journals (Sweden)

    Ahn Sun-A

    2007-01-01

    Full Text Available Abstract Background Glutathione S-transferases are a group of enzymes that participate in detoxification and defense mechanisms against toxic carcinogens and other compounds. These enzymes play an important role in human carcinogenesis. In the present study, we sought to determine whether GSTT2 promoter single nucleotide polymorphisms (SNPs are associated with colorectal cancer risk. Methods A total of 436 colorectal cancer patients and 568 healthy controls were genotyped for three GSTT2 promoter SNPs (-537G>A, -277T>C and -158G>A, using real-time TaqMan assay and direct sequencing. An electrophoretic mobility shift assay (EMSA was performed to determine the effects of polymorphisms on protein binding to the GSTT2 promoter. Results The -537A allele (-537G/A or A/A was significantly associated with colorectal cancer risk (OR = 1.373, p = 0.025, while the -158A allele (-158G/A or A/A was involved in protection against colorectal cancer (OR = 0.539, p = 0.032. Haplotype 2 (-537A, -277T, -158G was significantly associated with colorectal cancer risk (OR = 1.386, p = 0.021, while haplotype 4 (-537G, -277C, -158A protected against colorectal cancer (OR = 0.539, p = 0.032. EMSA data revealed lower promoter binding activity in the -537A allele than its -537G counterpart. Conclusion Our results collectively suggest that SNPs and haplotypes of the GSTT2 promoter region are associated with colorectal cancer risk in the Korean population.

  6. The chemopreventive action of bromelain, from pineapple stem (Ananas comosus L.), on colon carcinogenesis is related to antiproliferative and proapoptotic effects.

    Science.gov (United States)

    Romano, Barbara; Fasolino, Ines; Pagano, Ester; Capasso, Raffaele; Pace, Simona; De Rosa, Giuseppe; Milic, Natasa; Orlando, Pierangelo; Izzo, Angelo A; Borrelli, Francesca

    2014-03-01

    Colorectal cancer is an important health problem across the world. Here, we investigated the possible antiproliferative/proapoptotic effects of bromelain (from the pineapple stem Ananas comosus L., family Bromeliaceae) in a human colorectal carcinoma cell line and its potential chemopreventive effect in a murine model of colon cancer. Proliferation and apoptosis were evaluated in human colon adenocarcinoma (Caco-2) cells by the (3) H-thymidine incorporation assay and caspase 3/7 activity measurement, respectively. Extracellular signal-related kinase (ERK) and Akt expression were evaluated by Western blot analysis, reactive oxygen species production by a fluorimetric method. In vivo, bromelain was evaluated using the azoxymethane murine model of colon carcinogenesis. Bromelain reduced cell proliferation and promoted apoptosis in Caco-2 cells. The effect of bromelain was associated to downregulation of pERK1/2/total, ERK, and pAkt/Akt expression as well as to reduction of reactive oxygen species production. In vivo, bromelain reduced the development of aberrant crypt foci, polyps, and tumors induced by azoxymethane. Bromelain exerts antiproliferative and proapoptotic effects in colorectal carcinoma cells and chemopreventive actions in colon carcinogenesis in vivo. Bromelain-containing foods and/or bromelain itself may represent good candidates for colorectal cancer chemoprevention. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  7. Concepts of threshold in mutagenesis and carcinogenesis.

    Science.gov (United States)

    Kirsch-Volders, M; Aardema, M; Elhajouji, A

    2000-01-03

    Although the existence of a threshold in the dose effect relationship is well documented for many, if not most, types of toxicological effects the existence of a threshold for the mutagenic effects of ionising radiation and of certain chemicals has been questioned since the middle of the century and only recently the question of thresholds for radiation and chemical carcinogenesis has been addressed. The essential facts for the interpretation of threshold dose-response curves are common to all type of effects and are: (i) the number and the identity of the target; (ii) the type and sensitivity of the endpoint used to quantify the effect. We therefore will first try to model the type of interactions which may be expected between a mutagen and its target and define from this whether a threshold dose-effect can be expected; in a second step the concept will be extended to heritable mutations and carcinogenesis.

  8. Global metabolic reprogramming of colorectal cancer occurs at adenoma stage and is induced by MYC.

    Science.gov (United States)

    Satoh, Kiyotoshi; Yachida, Shinichi; Sugimoto, Masahiro; Oshima, Minoru; Nakagawa, Toshitaka; Akamoto, Shintaro; Tabata, Sho; Saitoh, Kaori; Kato, Keiko; Sato, Saya; Igarashi, Kaori; Aizawa, Yumi; Kajino-Sakamoto, Rie; Kojima, Yasushi; Fujishita, Teruaki; Enomoto, Ayame; Hirayama, Akiyoshi; Ishikawa, Takamasa; Taketo, Makoto Mark; Kushida, Yoshio; Haba, Reiji; Okano, Keiichi; Tomita, Masaru; Suzuki, Yasuyuki; Fukuda, Shinji; Aoki, Masahiro; Soga, Tomoyoshi

    2017-09-12

    Cancer cells alter their metabolism for the production of precursors of macromolecules. However, the control mechanisms underlying this reprogramming are poorly understood. Here we show that metabolic reprogramming of colorectal cancer is caused chiefly by aberrant MYC expression. Multiomics-based analyses of paired normal and tumor tissues from 275 patients with colorectal cancer revealed that metabolic alterations occur at the adenoma stage of carcinogenesis, in a manner not associated with specific gene mutations involved in colorectal carcinogenesis. MYC expression induced at least 215 metabolic reactions by changing the expression levels of 121 metabolic genes and 39 transporter genes. Further, MYC negatively regulated the expression of genes involved in mitochondrial biogenesis and maintenance but positively regulated genes involved in DNA and histone methylation. Knockdown of MYC in colorectal cancer cells reset the altered metabolism and suppressed cell growth. Moreover, inhibition of MYC target pyrimidine synthesis genes such as CAD, UMPS, and CTPS blocked cell growth, and thus are potential targets for colorectal cancer therapy.

  9. High occurrence of Fusobacterium nucleatum and Clostridium difficile in the intestinal microbiota of colorectal carcinoma patients

    Directory of Open Access Journals (Sweden)

    Márcia H. Fukugaiti

    2015-01-01

    Full Text Available AbstractColorectal carcinoma is considered the fourth leading cause of cancer deaths worldwide. Several microorganisms have been associated with carcinogenesis, including Enterococcus spp., Helicobacter pylori, enterotoxigenic Bacteroides fragilis, pathogenic E. coli strains and oral Fusobacterium. Here we qualitatively and quantitatively evaluated the presence of oral and intestinal microorganisms in the fecal microbiota of colorectal cancer patients and healthy controls. Seventeen patients (between 49 and 70 years-old visiting the Cancer Institute of the Sao Paulo State were selected, 7 of whom were diagnosed with colorectal carcinoma. Bacterial detection was performed by qRT-PCR. Although all of the tested bacteria were detected in the majority of the fecal samples, quantitative differences between the Cancer Group and healthy controls were detected only for F. nucleatum and C. difficile. The three tested oral microorganisms were frequently observed, suggesting a need for furthers studies into a potential role for these bacteria during colorectal carcinoma pathogenesis. Despite the small number of patients included in this study, we were able to detect significantly more F. nucleatumand C. difficile in the Cancer Group patients compared to healthy controls, suggesting a possible role of these bacteria in colon carcinogenesis. This finding should be considered when screening for colorectal cancer.

  10. Study of chemical and radiation induced carcinogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Chmura, A.

    1995-11-01

    The study of chemical and radiation induced carcinogenesis has up to now based many of its results on the detection of genetic aberrations using the fluorescent in situ hybridization (FISH) technique. FISH is time consuming and this tends to hinder its use for looking at large numbers of samples. We are currently developing new technological advances which will increase the speed, clarity and functionality of the FISH technique. These advances include multi-labeled probes, amplification techniques, and separation techniques.

  11. [Oxidative stress in prostate hypertrophy and carcinogenesis].

    Science.gov (United States)

    Przybyszewski, Waldemar M; Rzeszowska-Wolny, Joanna

    2009-07-20

    Aging, significant impairment of the oxidation/reduction balance, infection, and inflammation are recognized risk factors of benign hyperplasia and prostate cancer. Chronic symptomatic and asymptomatic prostate inflammatory processes generate significantly elevated levels of reactive oxygen and nitrogen species, and halogenated compounds. Prostate cancer patients showed significantly higher lipid peroxidation and lower antioxidant levels in peripheral blood than healthy controls, whereas patients with prostate hyperplasia did not show such symptoms. Oxidative/nitrosative/halogenative stress causes DNA modifications leading to genome instability that may initiate carcinogenesis; however, it was shown that oxidative damage alone is not sufficient to initiate this process. Peroxidation products induced by reactive oxygen and nitrogen species seem to take part in epigenetic mechanisms regulating genome activity. One of the most common changes occurring in more than 90% of all analyzed prostate cancers is the silencing of GSTP1 gene activity. The gene encodes glutathione transferase, an enzyme participating in detoxification processes. Prostate hyperplasia is often accompanied by chronic inflammation and such a relationship was not observed in prostate cancer. The participation of infection and inflammation in the development of hyperplasia is unquestionable and these factors probably also take part in initiating the early stages of prostate carcinogenesis. Thus it seems that therapeutic strategies that prevent genome oxidative damage in situations involving oxidative/nitrosative/halogenative stress, i.e. use of antioxidants, plant steroids, antibiotics, and non-steroidal anti-inflammatory drugs, could help prevent carcinogenesis.

  12. Oxidative stress in prostate hypertrophy and carcinogenesis

    Directory of Open Access Journals (Sweden)

    Waldemar M. Przybyszewski

    2009-07-01

    Full Text Available Aging, significant impairment of the oxidation/reduction balance, infection, and inflammation are recognized risk factors of benign hyperplasia and prostate cancer. Chronic symptomatic and asymptomatic prostate inflammatory processes generate significantly elevated levels of reactive oxygen and nitrogen species, and halogenated compounds. Prostate cancer patients showed significantly higher lipid peroxidation and lower antioxidant levels in peripheral blood than healthy controls, whereas patients with prostate hyperplasia did not show such symptoms. Oxidative/nitrosative/halogenative stress causes DNA modifications leading to genome instability that may initiate carcinogenesis; however, it was shown that oxidative damage alone is not sufficient to initiate this process. Peroxidation products induced by reactive oxygen and nitrogen species seem to take part in epigenetic mechanisms regulating genome activity. One of the most common changes occurring in more than 90�0of all analyzed prostate cancers is the silencing of GSTP1 gene activity. The gene encodes glutathione transferase, an enzyme participating in detoxification processes. Prostate hyperplasia is often accompanied by chronic inflammation and such a relationship was not observed in prostate cancer. The participation of infection and inflammation in the development of hyperplasia is unquestionable and these factors probably also take part in initiating the early stages of prostate carcinogenesis. Thus it seems that therapeutic strategies that prevent genome oxidative damage in situations involving oxidative/nitrosative/halogenative stress, i.e. use of antioxidants, plant steroids, antibiotics, and non-steroidal anti-inflammatory drugs, could help prevent carcinogenesis.

  13. Inhibition of carcinogenesis by retinoids. [Review

    Energy Technology Data Exchange (ETDEWEB)

    Nettesheim, P.

    1979-01-01

    Progress made in recent years in the search for retinoids with anticarcinogenic activity is reviewed. There are many studies to be found in the literature which show no substantial effect of retinoids on carcinogenesis or tumor growth. Some of these negative findings may be related to the carcinogen dose used, the type of retinoid used, the dose, dose schedule or mode of administration of the retinoid. Others may indicate that the particular type of tumor or tumor system is, indeed, refractory to retinoids in general or to those retinoids that were tested. A great gap still exists in our knowledge concerning the pharmake-kinetics of most retinoids their availability to various normal and cancerous tissues, and the role and existence of transport and binding proteins. There are studies which indicate that under certain conditions, particularly conditions of topical application, some retinoids may even enhance carcinogenesis. It seems, however, indisputable by now that some retinoids are effective inhibitors of carcinogenesis in some organ systems and can even inhibit the growth of some established tumors. While the mechanisms of these inhibitory effects are presently not understood, it does seem clear that they are not mediated via the cytotoxic mechanisms typical of chemotherapeutic agents. The hope that retinoids might become an effective tool to halt the progression of some neoplastic diseases, seems to be justified.

  14. Metachronous colorectal carcinoma

    DEFF Research Database (Denmark)

    Bülow, Steffen; Svendsen, L B; Mellemgaard, A

    1990-01-01

    During the period 1943-67, 903 Danish patients aged less than 40 years had colorectal carcinoma. The patients were followed up for up to 41 years and during this period 44 of 501 (9 per cent) operated on for cure developed a metachronous colorectal carcinoma. The cumulative risk of a metachronous...... colorectal carcinoma was 30 per cent after up to 41 years of observation. The occurrence of a metachronous colorectal carcinoma was evenly distributed in the observation period. The cumulative survival rate after operation for a metachronous colorectal carcinoma was 41 per cent after 20 years of observation....... We propose a lifelong follow-up programme after resection of colorectal carcinoma for cure in this age group, including annual Hemoccult test and colonoscopy at 3-year intervals....

  15. Clinical and Biological Features of Interval Colorectal Cancer.

    Science.gov (United States)

    Lee, Yu Mi; Huh, Kyu Chan

    2017-05-01

    Interval colorectal cancer (I-CRC) is defined as a CRC diagnosed within 60 months after a negative colonoscopy, taking into account that 5 years is the "mean sojourn time." It is important to prevent the development of interval cancer. The development of interval colon cancer is associated with female sex, old age, family history of CRC, comorbidities, diverticulosis, and the skill of the endoscopist. During carcinogenesis, sessile serrated adenomas/polyps (SSA/Ps) share many genomic and colonic site characteristics with I-CRCs. The clinical and biological features of I-CRC should be elucidated to prevent the development of interval colon cancer.

  16. Polymorphisms in fatty acid metabolism-related genes are associated with colorectal cancer risk

    DEFF Research Database (Denmark)

    Hoeft, B.; Linseisen, J.; Beckmann, L.

    2010-01-01

    Colorectal cancer (CRC) is the third most common malignant tumor and the fourth leading cause of cancer death worldwide. The crucial role of fatty acids for a number of important biological processes suggests a more in-depth analysis of inter-individual differences in fatty acid metabolizing genes...... as contributing factor to colon carcinogenesis. We examined the association between genetic variability in 43 fatty acid metabolism-related genes and colorectal risk in 1225 CRC cases and 2032 controls participating in the European Prospective Investigation into Cancer and Nutrition study. Three hundred...... variants with CRC risk. Our results support the key role of prostanoid signaling in colon carcinogenesis and suggest a relevance of genetic variation in fatty acid metabolism-related genes and CRC risk....

  17. Epigenetics and Colorectal Cancer

    Science.gov (United States)

    Lao, Victoria Valinluck; Grady, William M.

    2012-01-01

    Colorectal cancer is a leading cause of cancer deaths in the world. It results from an accumulation of genetic and epigenetic changes in colon epithelial cells that transforms them into adenocarcinomas. There have been major advances in our understanding of cancer epigenetics over the last decade, particularly regarding aberrant DNA methylation. Assessment of the colon cancer epigenome has revealed that virtually all colorectal cancers have aberrantly methylated genes and the average colorectal cancer methylome has hundreds to thousands of abnormally methylated genes. As with gene mutations in the cancer genome, a subset of these methylated genes, called driver genes, is presumed to play a functional role in colorectal cancer. The assessment of methylated genes in colorectal cancers has also revealed a unique molecular subgroup of colorectal cancers called CpG Island Methylator Phenotype (CIMP) cancers; these tumors have a particularly high frequency of methylated genes. The advances in our understanding of aberrant methylation in colorectal cancer has led to epigenetic alterations being developed as clinical biomarkers for diagnostic, prognostic, and therapeutic applications. Progress in the assessment of epigenetic alterations in colorectal cancer and their clinical applications has shown that these alterations will be commonly used in the near future as molecular markers to direct the prevention and treatment of colorectal cancer. PMID:22009203

  18. Colorectal Cancer Screening

    Science.gov (United States)

    ... Types Bladder Cancer Breast Cancer Colorectal Cancer Kidney (Renal Cell) Cancer Leukemia Liver Cancer Lung Cancer Lymphoma Pancreatic Cancer Prostate Cancer Skin Cancer Thyroid Cancer Uterine Cancer All ...

  19. Zinc finger protein 278, a potential oncogene in human colorectal cancer

    Institute of Scientific and Technical Information of China (English)

    Xiaoqing Tian; Danfeng Sun; Yanjie Zhang; Shuliang Zhao; Hua Xiong; Jingyuan Fang

    2008-01-01

    Zinc finger protein 278 (ZNF278) is a novel Krueppel Cys2-His2-type zinc finger protein that is ubiquitously distributed in human tissues. Whether ZNF278 is related to the development of colorectal cancer is still unclear. The transcriptional level of ZNF278 was studied in colorectal cancer by real-time polymerase chain reaction. The results showed that ZNF278 expression was increased in 53% of colorectal cancer tissues compared to corresponding non-cancerous tissues. The transcriptional down-regulation of ZNF278 was detected in only three (6%) human colorectal cancer tissues compared to corresponding non-cancer tissues. No significant difference was detected in 19 (41%) pairs of samples.However, we failed to find a significant association between the up-regulation of ZNF278 transcription and age, sex, the degree of infiltration, or the tumor size of colorectal cancer.To study the function of ZNF278 in colorectal carcinogenesis,the colon cancer cell line SW1116 was stably transfected with a wild-type ZNF278 plasmid to construct an overexpression system, and was transiently transfected with the small interfering RNA of ZNF278 to construct a ZNF278 knockdown system. Cell proliferation was assessed with 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide dye and a cell counter. The results show that ZNF278 promotes cell growth, and its knockdown suppresses cell proliferation. ZNF278 could be a potential proto-oncogene in colorectal cancer.

  20. Antitumor magnetic hyperthermia induced by RGD-functionalized Fe3O4 nanoparticles, in an experimental model of colorectal liver metastases

    Directory of Open Access Journals (Sweden)

    Oihane K. Arriortua

    2016-10-01

    Full Text Available This work reports important advances in the study of magnetic nanoparticles (MNPs related to their application in different research fields such as magnetic hyperthermia. Nanotherapy based on targeted nanoparticles could become an attractive alternative to conventional oncologic treatments as it allows a local heating in tumoral surroundings without damage to healthy tissue. RGD-peptide-conjugated MNPs have been designed to specifically target αVβ3 receptor-expressing cancer cells, being bound the RGD peptides by “click chemistry” due to its selectivity and applicability. The thermal decomposition of iron metallo-organic precursors yield homogeneous Fe3O4 nanoparticles that have been properly functionalized with RGD peptides, and the preparation of magnetic fluids has been achieved. The nanoparticles were characterized by transmission electron microscopy (TEM, vibrating sample magnetometry (VSM, electron magnetic resonance (EMR spectroscopy and magnetic hyperthermia. The nanoparticles present superparamagnetic behavior with very high magnetization values, which yield hyperthermia values above 500 W/g for magnetic fluids. These fluids have been administrated to rats, but instead of injecting MNP fluid directly into liver tumors, intravascular administration of MNPs in animals with induced colorectal tumors has been performed. Afterwards the animals were exposed to an alternating magnetic field in order to achieve hyperthermia. The evolution of an in vivo model has been described, resulting in a significant reduction in tumor viability.

  1. [In vitro and in vivo effects of mango pulp (Mangifera indica cv. Azucar) in colon carcinogenesis].

    Science.gov (United States)

    Corrales-Bernal, Andrea; Amparo Urango, Luz; Rojano, Benjamín; Maldonado, Maria Elena

    2014-03-01

    Mango pulp contains ascorbic acid, carotenoids, polyphenols, terpenoids and fiber which are healthy and could protect against colon cancer. The aim of this study was to evaluate the antiproliferative and preventive capacity of an aqueous extract of Mangifera indica cv. Azúcar on a human colon adenocarcinoma cell line (SW480) and in a rodent model of colorectal cancer, respectively. The content of total phenolics, flavonoids and carotenoids were also analyzed in the extract. SW480 cell growth was inhibited in a dose and time dependent manner by 22.3% after a 72h exposure to the extract (200 µg/ mL). Colon carcinogenesis was initiated in Balb/c mice by two intra-peritoneal injections of azoxymethane (AOM) at the third and fourth week of giving mango in drinking water (0.3%, 0.6%, 1.25%). After 10 weeks of treatment, in the colon of mice receiving 0.3% mango, aberrant crypt foci formation was inhibited more than 60% (p=0,05) and the inhibition was dose-dependent when compared with controls receiving water. These results show that mango pulp, a natural food, non toxic, part of human being diet, contains bioactive compounds able to reduce growth of tumor cells and to prevent the appearance of precancerous lesions in colon during carcinogenesis initiation.

  2. Curcumin ameliorates the tumor-enhancing effects of a high-protein diet in an azoxymethane-induced mouse model of colon carcinogenesis.

    Science.gov (United States)

    Byun, So-Young; Kim, Dan-Bi; Kim, Eunjung

    2015-08-01

    An increasing number of reports suggest that a high-protein diet (HPD) is associated with an increased risk for colorectal cancer (CRC). One of the proposed mechanisms is that an HPD increases the delivery of protein to the colon and generates various toxic metabolites that contribute to colon carcinogenesis. Curcumin was shown to exert significant preventive properties against CRC. We therefore hypothesized that curcumin can reverse the tumor-enhancing effects of an HPD. This study examined the effects of curcumin on the development of azoxymethane (AOM)-induced colorectal tumors in HPD-fed mice. A total of 30 female Balb/c mice were randomly divided into 3 groups: those fed a normal diet (20% casein), those fed an HPD (HPD; 50% casein), and those fed an HPD supplemented with curcumin (HPDC; 0.02% curcumin). The mice were subjected to an AOM-dextran sodium sulfate colon carcinogenesis protocol. Mice in the HPDC group exhibited a significant (40%) reduction in colorectal tumor multiplicity when compared with those in the HPD group. The expression of colonic inflammatory proteins (cyclooxygenase-2 and inducible nitric oxide synthase), the levels of plasma inflammatory markers (nitric oxide and tumor necrosis factor-α), fecal ammonia, short- and branched-chain fatty acid levels, and the rate of colonocyte proliferation were significantly lower in the HPDC than the HPD group. In conclusion, curcumin inhibited the development of colorectal tumors in an AOM-induced mouse model of colon carcinogenesis by attenuating colonic inflammation, proliferation, and toxic metabolite production. Curcumin might be useful in the chemoprevention of CRC in individuals consuming an HPD. Copyright © 2015 Elsevier Inc. All rights reserved.

  3. Dietary methyl donors, methyl metabolizing enzymes, and epigenetic regulators: Diet-gene interactions and promoter CpG island hypermethylation in colorectal cancer

    NARCIS (Netherlands)

    Vogel, S. de; Wouters, K.A.D.; Gottschalk, R.W.H.; Schooten, F.J. van; Goeij, A.F.P.M. de; Bruïne, A.P. de; Goldbohm, R.A.; Brandt, P.A. van den; Engeland, M. van; Weijenberg, M.P.

    2011-01-01

    Dietary methyl donors might influence DNA methylation during carcinogenesis of colorectal cancer (CRC). Among 609 CRC cases and 1,663 subcohort members of the Netherlands Cohort Study on diet and cancer (n = 120,852), we estimated CRC risk according to methyl donor intake across genotypes of folate

  4. Helicobacter pylori infection and gastric carcinogenesis in rodent models.

    Science.gov (United States)

    Tsukamoto, Tetsuya; Toyoda, Takeshi; Mizoshita, Tsutomu; Tatematsu, Masae

    2013-03-01

    Helicobacter pylori infection is an important factor for gastric carcinogenesis in human. In carcinogen-treated Mongolian gerbils, H. pylori infection enhances stomach carcinogenesis, while infection alone induced severe hyperplasia called heterotopic proliferative glands. A high-salt diet or early acquisition of the bacteria exacerbates inflammation and carcinogenesis. Oxygen radical scavengers or anti-inflammatory chemicals as well as eradication of H. pylori are effective to prevent carcinogenesis. H. pylori-associated inflammation induces intestinal metaplasia and intestinalization of stomach cancers independently. It is necessary to control cancer development not only in H. pylori-positive cases but also in H. pylori-negative metaplastic gastritis.

  5. Promoter Methylation Precedes Chromosomal Alterations in Colorectal Cancer Development

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    Sarah Derks

    2006-01-01

    Full Text Available Background: Colorectal cancers are characterized by genetic and epigenetic alterations. This study aimed to explore the timing of promoter methylation and relationship with mutations and chromosomal alterations in colorectal carcinogenesis. Methods: In a series of 47 nonprogressed adenomas, 41 progressed adenomas (malignant polyps, 38 colorectal carcinomas and 18 paired normal tissues, we evaluated promoter methylation status of hMLH1, O6MGMT, APC, p14ARF, p16INK4A, RASSF1A, GATA-4, GATA-5, and CHFR using methylation-specific PCR. Mutation status of TP53, APC and KRAS were studied by p53 immunohistochemistry and sequencing of the APC and KRAS mutation cluster regions. Chromosomal alterations were evaluated by comparative genomic hybridization. Results: Our data demonstrate that nonprogressed adenomas, progressed adenomas and carcinomas show similar frequencies of promoter methylation for the majority of the genes. Normal tissues showed significantly lower frequencies of promoter methylation of APC, p16INK4A, GATA-4, and GATA-5 (P-values: 0.02, 0.02, 1.1×10−5 and 0.008 respectively. P53 immunopositivity and chromosomal abnormalities occur predominantly in carcinomas (P values: 1.1×10−5 and 4.1×10−10. Conclusions: Since promoter methylation was already present in nonprogressed adenomas without chromosomal alterations, we conclude that promoter methylation can be regarded as an early event preceding TP53 mutation and chromosomal abnormalities in colorectal cancer development.

  6. Oral administration of sodium butyrate reduces chemically-induced preneoplastic lesions in experimental carcinogenesis Administração oral de butirato de sódio reduz lesões pré-neoplásicas quimicamente induzidas na carcinogênese experimental

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    Maria do Carmo Gouveia Peluzio

    2009-10-01

    Full Text Available OBJECTIVE: The objective was to assess the effects of oral administration of sodium butyrate on colon carcinogenesis. METHODS: Carcinogenesis in adult male Wistar rats was induced with 1.2-dimethylhydrazine injections at a dose of 40mg/kg of body weight. A solution of sodium butyrate (3.4% was given ad libitum for 4 weeks (butyrate group, n=16 instead of water (control group, n=9. Rats were killed 17 weeks after 1.2-dimethylhydrazine administration. Aberrant crypt foci and expression of the messenger ribonucleic acid (mRNA of cyclins D1 and E were quantified in the colon. Alterations in the fatty acid profile of the colon, liver, intra-abdominal fat and feces were also analyzed. RESULTS: A significant decrease in aberrant crypt foci was found in the group taking butyrate. No differences were found between the groups in the mRNA expression of cyclins D1 and E. Nevertheless, butyrate intake decreased the content of stearic and oleic acids in the intra-abdominal fat and docosahexaenoic acid in the liver. Moreover, these rats presented higher percentages of linoleic acid in the intra-abdominal fat than control rats. CONCLUSION: The data indicate that butyrate use in rats reduced preneoplastic lesions and changes in the intra-abdominal fat and fatty acid profile of the liver, commonly found in colon carcinogenesis.OBJETIVO: Avaliar o efeito da administração oral de butirato de sódio na carcinogênese do cólon. MÉTODOS: A carcinogênese em ratos Wistar foi induzida com injeções de 1,2-dimetilhidrazina na dose de 40mg/kg de peso corporal. A solução de butirato de sódio (3,4% foi oferecida ad libitum por 4 semanas (grupo butirato, n=16, em substituição à água (grupo controle, n=9. Os ratos foram sacrificados na 17ª semana após tratamento com a 1,2-dimetilhidrazina. Focos de criptas aberrantes e a expressão dos genes para o ácido ribonucléico mensageiro (RNAm das ciclinas D1 e E foram quantificadas no cólon. Alterações no perfil de

  7. Synchronous colorectal liver metastases

    NARCIS (Netherlands)

    A.E.M. van der Pool (Anne)

    2011-01-01

    textabstractColorectal cancer is one of the most common malignancies worldwide and ranks second in cancer-related deaths in many parts of the Western world. Once in the lymph or blood vessels, colorectal cancer can quickly spread and the liver is known to be a favourable site for metastases. The

  8. Mechanisms of carcinogenesis prevention by flavonoids

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    G. A. Belitsky

    2014-01-01

    Full Text Available The mechanisms of anticancerogenic effects of flavanoids and isocyanates from the plants widely consumed in the midland belt of Russia were reviewed. Data of studies both in vitro and in vivo were analyzed. Special attention was paid to inhibition of targets responsible for carcinogen metabolic activation, carcinogenesis promotion and tumor progression as well as neoangiogenesis. Besides that the antioxidant properties of flavonoids and their effects on cell cycle regulation, apoptosis initiation and cell mobility were considered.

  9. Can colorectal cancer mass-screening organization be evidence-based? Lessons from failures: The experimental and pilot phases of the Lazio program

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    Valle Sabrina

    2008-09-01

    Full Text Available Abstract Background Screening programmes should be organized to translate theoretical efficacy into effectiveness. An evidence-based organizational model of colorectal cancer screening (CRCS should assure feasibility and high compliance. Methods A multidisciplinary Working Group (WG, reviewed literature and guidelines to define evidence-based recommendations. The WG identified the need for further local studies: physicians' CRCS attitudes, the effect of test type and provider on compliance, and individual reasons for non-compliance. A survey of digestive endoscopy services was conducted. A feasibility study on a target population of 300.000 has begun. Results Based on the results of population trials and on literature review the screening strategy adopted was Faecal Occult Blood Test (FOBT every two years for 50–74 year olds and, for positives, colonoscopy. The immunochemical test was chosen because it has 20% higher compliance than the Guaiac. GPs were chosen as the preferred provider also for higher compliance. Since we observed that distance is the major determinant of non-compliance, we choose GPs because they are the closest providers, both geographically and emotionally, to the public. The feasibility study showed several barriers: GP participation was low, there were administrative problems to involve GPs; opportunistic testing by the GPs; difficulties in access to Gastroenterology centres; difficulties in gathering colonoscopy results; little time given to screening activity by the gastroenterology centre. Conclusion The feasibility study highlighted several limits of the model. Most of the barriers that emerged were consequences of organisational choices not supported by evidence. The principal limit was a lack of accountability by the participating centres.

  10. The Anticancer Role of Capsaicin in Experimentallyinduced Lung Carcinogenesis

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    Pandi Anandakumar

    2015-06-01

    Full Text Available Objectives: Capsaicin (CAP is the chief pungent principle found in the hot red peppers and the chili peppers that have long been used as spices, food additives and drugs. This study investigated the anticancer potential of CAP through its ability to modify extracellular matrix components and proteases during mice lung carcinogenesis. Methods: Swiss albino mice were treated with benzo(a pyrene (50 mg/kg body weight dissolved in olive oil orally twice a week for four successive weeks to induce lung cancer at the end of 14th week. CAP was administrated (10 mg/kg body weight dissolved in olive oil intraperitoneally. Extracellular matrix components were assayed; Masson’s trichome staining of lung tissues was performed. Western blot analyses of matrix metalloproteases 2 and 9 were also carried out. Results: In comparison with the control animals, animals in which benzo(apyrene had induced lung cancer showed significant increases in extracellular matrix components such as collagen (hydroxy proline, elastin, uronic acid and hexosamine and in glycosaminoglycans such as hyaluronate, chondroitin sulfate, keratan sulfate and dermatan sulfate. The above alterations in extracellular matrix components were effectively counteracted in benzo(apyrene along with CAP supplemented animals when compared to benzo(a pyrene alone supplemented animals. The results of Masson’s trichome staining for collagen and of, immunoblotting analyses of matrix metalloproteases 2 and 9 further supported the biochemical findings. Conclusion: The apparent potential of CAP in modulating extracellular matrix components and proteases suggests that CAP plays a chemomodulatory and anti- cancer role working against experimentally induced lung carcinogenesis.

  11. HDAC up-regulation in early colon field carcinogenesis is involved in cell tumorigenicity through regulation of chromatin structure.

    Science.gov (United States)

    Stypula-Cyrus, Yolanda; Damania, Dhwanil; Kunte, Dhananjay P; Cruz, Mart Dela; Subramanian, Hariharan; Roy, Hemant K; Backman, Vadim

    2013-01-01

    Normal cell function is dependent on the proper maintenance of chromatin structure. Regulation of chromatin structure is controlled by histone modifications that directly influence chromatin architecture and genome function. Specifically, the histone deacetylase (HDAC) family of proteins modulate chromatin compaction and are commonly dysregulated in many tumors, including colorectal cancer (CRC). However, the role of HDAC proteins in early colorectal carcinogenesis has not been previously reported. We found HDAC1, HDAC2, HDAC3, HDAC5, and HDAC7 all to be up-regulated in the field of human CRC. Furthermore, we observed that HDAC2 up-regulation is one of the earliest events in CRC carcinogenesis and observed this in human field carcinogenesis, the azoxymethane-treated rat model, and in more aggressive colon cancer cell lines. The universality of HDAC2 up-regulation suggests that HDAC2 up-regulation is a novel and important early event in CRC, which may serve as a biomarker. HDAC inhibitors (HDACIs) interfere with tumorigenic HDAC activity; however, the precise mechanisms involved in this process remain to be elucidated. We confirmed that HDAC inhibition by valproic acid (VPA) targeted the more aggressive cell line. Using nuclease digestion assays and transmission electron microscopy imaging, we observed that VPA treatment induced greater changes in chromatin structure in the more aggressive cell line. Furthermore, we used the novel imaging technique partial wave spectroscopy (PWS) to quantify nanoscale alterations in chromatin. We noted that the PWS results are consistent with the biological assays, indicating a greater effect of VPA treatment in the more aggressive cell type. Together, these results demonstrate the importance of HDAC activity in early carcinogenic events and the unique role of higher-order chromatin structure in determining cell tumorigenicity.

  12. HDAC up-regulation in early colon field carcinogenesis is involved in cell tumorigenicity through regulation of chromatin structure.

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    Yolanda Stypula-Cyrus

    Full Text Available Normal cell function is dependent on the proper maintenance of chromatin structure. Regulation of chromatin structure is controlled by histone modifications that directly influence chromatin architecture and genome function. Specifically, the histone deacetylase (HDAC family of proteins modulate chromatin compaction and are commonly dysregulated in many tumors, including colorectal cancer (CRC. However, the role of HDAC proteins in early colorectal carcinogenesis has not been previously reported. We found HDAC1, HDAC2, HDAC3, HDAC5, and HDAC7 all to be up-regulated in the field of human CRC. Furthermore, we observed that HDAC2 up-regulation is one of the earliest events in CRC carcinogenesis and observed this in human field carcinogenesis, the azoxymethane-treated rat model, and in more aggressive colon cancer cell lines. The universality of HDAC2 up-regulation suggests that HDAC2 up-regulation is a novel and important early event in CRC, which may serve as a biomarker. HDAC inhibitors (HDACIs interfere with tumorigenic HDAC activity; however, the precise mechanisms involved in this process remain to be elucidated. We confirmed that HDAC inhibition by valproic acid (VPA targeted the more aggressive cell line. Using nuclease digestion assays and transmission electron microscopy imaging, we observed that VPA treatment induced greater changes in chromatin structure in the more aggressive cell line. Furthermore, we used the novel imaging technique partial wave spectroscopy (PWS to quantify nanoscale alterations in chromatin. We noted that the PWS results are consistent with the biological assays, indicating a greater effect of VPA treatment in the more aggressive cell type. Together, these results demonstrate the importance of HDAC activity in early carcinogenic events and the unique role of higher-order chromatin structure in determining cell tumorigenicity.

  13. Chemopreventive Effects of Azadirachta indica on Cancer Marker Indices and Ultrastructural Changes During 1,2-Dimethylhydrazine-Induced Colon Carcinogenesis in Rats.

    Science.gov (United States)

    Liu, Ning; Sun, Bo; Wu, Peiwei; Wei, Xi

    2015-09-01

    The present study elucidated the prospective of Azadirachta indica supplementation, if any, in affording chemoprevention by modulating the altered cancer markers and ultrastructural changes in DMH-induced colorectal carcinogenesis in rats. The rats were segregated into four groups viz., normal control, DMH treated, A. indica treated, and DMH+AI treated. Initiation and induction of colon carcinogenesis were achieved through weekly subcutaneous injections of DMH (30 mg/kg body weight) for both 10 and 20 weeks. A. indica extract was supplemented to rats at a dose rate of 100 mg/kg body weight of animals thrice a week on alternative days, ad libitum for two different time durations of 10 and 20 weeks. The study observed a significant increase in the number of aberrant crypt foci in colons of DMH-treated rats at both the time intervals which were decreased significantly upon AI supplementation. Also, a significant increase was seen in the enzyme activity of alkaline phosphatase, which, however, was moderated upon AI administration to DMH-treated rats. Changes in the ultrastructural architecture of colonic cells were apparent following both the treatment schedules of DMH; however, the changes were prominent following 20 weeks of DMH treatment. The most obvious changes were seen in the form of altered nuclear shape and disruption of cellular integrity, which were appreciably improved upon AI supplementation. In conclusion, the study shows the chemopreventive abilities of AI against DMH-induced colorectal carcinogenesis in rats.

  14. Modifying factors in urinary bladder carcinogenesis

    Science.gov (United States)

    Ito, Nobuyuki; Fukushima, Shoji; Shirai, Tomoyuki; Nakanishi, Keisuke; Hasegawa, Ryohei; Imaida, Katsumi

    1983-01-01

    N-Butyl-N-(4-hydroxybutyl)nitrosamine (BBN) is a potent carcinogen in the urinary bladder of animals. The BBN model of bladder cancer is an excellent model of human urinary bladder cancer and has already led to a greater knowledge of its pathogenesis. In our studies, histogenesis and morphological characteristics of BBN urinary bladder cancer were analyzed in different animal species such as rats, mice, hamsters and guinea pigs and also in different rat strains. Papillary or nodular hyperplasia (PN hyperplasia) is found to be a preneoplastic lesion of the rat urinary bladder. Therefore, the promoting and inhibitory effects of various chemicals in two-stage urinary bladder carcinogenesis were judged by measuring PN hyperplasia in rats. Dose-dependent and organ-specific effects of the urinary bladder promoter, saccharin, in the induction of PN hyperplasia were shown in rats after initiation by BBN. The promoting effect of saccharin was seen more clearly in the urinary bladder of rats after potent initiation. A strain difference in susceptibility of the urinary bladder to the promoter was also shown. These results suggest that the above various factors may also have modifying activities on urinary bladder carcinogenesis in man. PMID:6832095

  15. DNA damage and aberrant crypt foci as putative biomarkers to evaluate the chemopreventive effect of annatto (Bixa orellana L.) in rat colon carcinogenesis.

    Science.gov (United States)

    Agner, Aniele R; Bazo, Ana P; Ribeiro, Lúcia R; Salvadori, Daisy M F

    2005-04-04

    Chemoprevention opens new perspectives in the prevention of cancer and other degenerative diseases. Use of target-organ biological models at the histological and genetic levels can markedly facilitate the identification of such potential chemopreventive agents. Colon cancer is one of the highest incidence rates throughout the world and some evidences have indicated carotenoids as possible agents that decrease the risk of colorectal cancer. In the present study, we evaluate the activity of annatto (Bixa orellana L.), a natural food colorant rich in carotenoid, on the formation of aberrant crypt foci (ACF) induced by dimethylhydrazine (DMH) in rat colon. Further, we investigate, the effect of annatto on DMH-induced DNA damage, by the comet assay. Male Wistar rats were given s.c. injections of DMH (40 mg/kg body wt.) twice a week for 2 weeks to induce ACF. They also received experimental diets containing annatto at 20, 200 or 1000 ppm for five 5 weeks before (pre-treatment), or 10 weeks after (post-treatment) DMH treatment. In both protocols the rats were sacrificed on week 15th. For the comet assay, the animals were fed with the same experimental diets for 2 weeks. Four hours before the sacrifice, the animals received an s.c. injection of DMH (40 mg/kg body wt.). Under such conditions, dietary administration of 1000 ppm annatto neither induce DNA damage in blood and colon cells nor aberrant crypt foci in rat distal colon. Conversely, annatto was successful in inhibiting the number of crypts/colon (animal), but not in the incidence of DMH-induced ACF, mainly when administered after DMH. However, no antigenotoxic effect was observed in colon cells. These findings suggest possible chemopreventive effects of annatto through their modulation of the cryptal cell proliferation but not at the initiation stage of colon carcinogenesis.

  16. INFLAMMATORY BOWEL DISEASE AND COLORECTAL CANCER, NUTRACEUTICAL ASPECTS.

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    Margherita Mazzola

    2016-04-01

    Full Text Available Nutraceuticals constitute a group of functional foods that provide added health benefits for various disorders including inflammatory bowel disease (IBD and colorectal cancer (CRC. The main groups of nutraceuticals include probiotics, prebiotics, omega 3 and antioxidants. Studies on Nutraceutical showed that this type of food possessed similar proprieties to drugs but with the benefit of not having side effects. This mini review shows that probiotics and prebiotics, when administered simultaneously with traditional therapies, reduce IBD symptoms and reduce synthesis of enzymes probably involved in colorectal carcinogenesis. Moreover, Omega 3 reduces the synthesis of inflammation mediators and prevents carcinogenesis through interaction with the signaling pathway NOTCH1/MMP9. Moreover, antioxidants reduce the inflammatory process by inhibiting the synthesis of inflammatory mediators, and inhibit the mechanisms of cell proliferation by inducing apoptosis. In brief, nutraceuticals have gained a huge clinical interest since they could be used along with traditional therapy. Bioavailability studies of nutraceutical supplements guarantee a correct intake of the substance by oral administration, a matter which would not have been possible to have entirely with the consumption of regular food only.

  17. [Standardized and structured histopathological evaluation of colorectal polyps: a practical checklist against the background of the new WHO classification].

    Science.gov (United States)

    Baretton, G B; Tannapfel, A; Schmitt, W

    2011-07-01

    Gastroenterologists removing colorectal polyps expect standardized and well-structured pathological reports, providing them with all relevant data for the further clinical management of the patient. Over the last year, a task force of clinicians and pathologists has developed a checklist to improve and harmonize endoscopic and pathological reporting of colorectal polyps. This checklist concentrates more on concrete recommendations from evidence-based guidelines and established international classifications for daily practice rather than detailed molecular pathological pathways of carcinogenesis. These recommendations are based on the current S3 guidelines for colorectal cancer (the chapter entitled "Management of colorectal polyps"), the histomorphological consensus manuscript of the GI working group of the German Society for Pathology, as well as the current WHO classification for tumors of the digestive system.

  18. Report of National Cancer Institute symposium: comparison of mechanisms of carcinogenesis by radiation and chemical agents. I. Common molecular mechanisms

    Energy Technology Data Exchange (ETDEWEB)

    Borg, D.C.

    1984-01-01

    Some aspects of molecular mechanisms common to radiation and chemical carcinogenesis are discussed, particularly the DNA damage done by these agents. Emphasis is placed on epidemiological considerations and on dose-response models used in risk assessment to extrapolate from experimental data obtained at high doses to the effects from long-term, low-level exposures. 3 references, 6 figures. (ACR)

  19. Detection of colorectal neoplasia

    DEFF Research Database (Denmark)

    Wilhelmsen, Michael; Christensen, Ib J.; Rasmussen, Louise

    2017-01-01

    Serological biomarkers may be an option for early detection of colorectal cancer (CRC). The present study assessed eight cancer-associated protein biomarkers in plasma from subjects undergoing first time ever colonoscopy due to symptoms attributable to colorectal neoplasia. Plasma AFP, CA19-9, CEA...... value was 18% and the negative predictive value was 97%. Combinations of serological protein biomarkers provided a significant identification of subjects with high risk of the presence of colorectal neoplasia. The present set of biomarkers could become important adjunct in early detection of CRC....

  20. Inflammation-associated serum and colon markers as indicators of dietary attenuation of colon carcinogenesis in ob/ob mice.

    Science.gov (United States)

    Mentor-Marcel, Roycelynn A; Bobe, Gerd; Barrett, Kathleen G; Young, Matthew R; Albert, Paul S; Bennink, Maurice R; Lanza, Elaine; Colburn, Nancy H

    2009-01-01

    Although inflammatory cytokines and obesity-associated serum proteins have been reported as biomarkers of colorectal adenoma risk in humans, little is known of biomarkers of response to interventions that attenuate tumorigenesis. Dietary navy beans and their fractions attenuate colon carcinogenesis in carcinogen-induced genetically obese mice. We hypothesized that this attenuation would be associated with changes in inflammatory cytokines and obesity-related serum proteins that may serve as measures of efficacy. ob/ob mice (n = 160) were injected with the carcinogen azoxymethane (AOM) to induce colon cancer and randomly placed on one of four diets (control, whole navy bean, bean residue fraction, or bean extract fraction) for 26 to 28 wk. Serum was analyzed for 14 inflammation- or obesity-related proteins, and colon RNA was analyzed for expression of 84 inflammation-associated genes. Six of 14 serum proteins were increased [i.e., interleukin (IL)-4, IL-5, IL-6, IL-10, IFN gamma, granulocyte macrophage colony-stimulating factor] in hyperplastic/dysplastic stages of colon carcinogenesis. Bean-fed mice had significantly higher monocyte chemoattractant protein-1 and lower IL-6 levels in serum. In colon mucosa, 55 of 84 inflammation-associated genes differed between AOM-induced and noninduced mice. Of the 55 AOM-induced genes, 5 were counteracted by bean diets, including IL-6 whose increase in expression levels was attenuated by bean diets in AOM-induced mice. In summary, IL-6 emerged as a serum protein that was increased in hyperplastic/dysplastic stages of colon carcinogenesis, but attenuated with bean-based diet in serum and colon mucosa. Changes in a subset of inflammation-associated serum proteins and colon gene expression may serve as response indicators of dietary attenuation of colon carcinogenesis.

  1. Apc-Mutant Kyoto Apc Delta (KAD Rats Are Susceptible to 4-NQO-Induced Tongue Carcinogenesis

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    Takuji Tanaka

    2014-07-01

    Full Text Available Despite widening interest in the possible association between infection/ inflammation and cancer development, knowledge of this issue in relation to oral cancer remains inadequate. This study aimed to determine the susceptibility of Apc-mutant Kyoto Apc Delta (KAD rats, which are vulnerable to developing inflammation-associated colorectal carcinogenesis, to 4-nitroquinoline 1-oxide (4-NQO-induced tongue carcinogenesis in order to clarify the role of inflammation in oral cancer. KAD (20 males and 22 females and F344/NS1c (22 males and 23 females rats received drinking water with or without 4-NQO (20 ppm for eight weeks. Histopathological and immunohistochemical analyses of the tongue were performed at week 20. Additionally, the mRNA expression of inflammatory cytokines in the tongue mucosa was determined at week 8. Tongue squamous cell carcinoma (SCC developed in the KAD and F344/NS1c rats that received 4-NQO. Regardless of gender, the incidence and multiplicity of tongue SCC were greater in the KAD rats than in the F344/NS1c rats. In addition, the multiplicity of tongue SCC in the female KAD rats was significantly greater than that observed in the male KAD (p < 0.01 and female F344/NS1c rats (p < 0.05. The levels of inflammation and the mRNA expression of inflammatory cytokines in the tongue in the 4-NQO-treated female KAD rats were the highest among the rats given 4-NQO. These results show that KAD rats, particularly females, are susceptible to 4-NQO-induced tongue carcinogenesis, suggesting the utility of models employing KAD rats for investigating the pathobiology of oral (tongue carcinogenesis associated with inflammation.

  2. Apc-Mutant Kyoto Apc Delta (KAD) Rats Are Susceptible to 4-NQO-Induced Tongue Carcinogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Tanaka, Takuji, E-mail: tmntt08@gmail.com [Department of Diagnostic Pathology (DDP) & Research Center of Diagnostic Pathology (RC-DiP), Gifu Municipal Hospital, 7-1 Kashima-Cho, Gifu 500-8513 (Japan); Department of Tumor Pathology, Gifu University Graduate School of Medicine, 1-1 Yanagido, Gifu 501-1194 (Japan); Shimizu, Masahito; Kochi, Takahiro; Shirakami, Yohei [Department of Internal Medicine/Gastroenterology, Gifu University Graduate School of Medicine, 1-1 Yanagido, Gifu 501-1194 (Japan); Mori, Takayuki [Department of Pharmacy, Ogaki Municipal Hospital, 4-86 Minaminokawa-cho, Ogaki 503-8502 (Japan); Watanabe, Naoki [Department of Diagnostic Pathology (DDP) & Research Center of Diagnostic Pathology (RC-DiP), Gifu Municipal Hospital, 7-1 Kashima-Cho, Gifu 500-8513 (Japan); Naiki, Takafumi [Department of Clinical Laboratory, Gifu Municipal Hospital, 7-1 Kashima-cho, Gifu 500-8513 (Japan); Moriwaki, Hisataka [Department of Internal Medicine/Gastroenterology, Gifu University Graduate School of Medicine, 1-1 Yanagido, Gifu 501-1194 (Japan); Yoshimi, Kazuto; Serikawa, Tadao; Kuramoto, Takashi [The Institute of Laboratory Animals, Graduate School of Medicine, Kyoto University, Yoshidakonoe-cho, Sakyo-ku, Kyoto 606-8501 (Japan)

    2014-07-21

    Despite widening interest in the possible association between infection/inflammation and cancer development, knowledge of this issue in relation to oral cancer remains inadequate. This study aimed to determine the susceptibility of Apc-mutant Kyoto Apc Delta (KAD) rats, which are vulnerable to developing inflammation-associated colorectal carcinogenesis, to 4-nitroquinoline 1-oxide (4-NQO)-induced tongue carcinogenesis in order to clarify the role of inflammation in oral cancer. KAD (20 males and 22 females) and F344/NS1c (22 males and 23 females) rats received drinking water with or without 4-NQO (20 ppm) for eight weeks. Histopathological and immunohistochemical analyses of the tongue were performed at week 20. Additionally, the mRNA expression of inflammatory cytokines in the tongue mucosa was determined at week 8. Tongue squamous cell carcinoma (SCC) developed in the KAD and F344/NS1c rats that received 4-NQO. Regardless of gender, the incidence and multiplicity of tongue SCC were greater in the KAD rats than in the F344/NS1c rats. In addition, the multiplicity of tongue SCC in the female KAD rats was significantly greater than that observed in the male KAD (p < 0.01) and female F344/NS1c rats (p < 0.05). The levels of inflammation and the mRNA expression of inflammatory cytokines in the tongue in the 4-NQO-treated female KAD rats were the highest among the rats given 4-NQO. These results show that KAD rats, particularly females, are susceptible to 4-NQO-induced tongue carcinogenesis, suggesting the utility of models employing KAD rats for investigating the pathobiology of oral (tongue) carcinogenesis associated with inflammation.

  3. Use of a chemically induced-colon carcinogenesis-prone Apc-mutant rat in a chemotherapeutic bioassay

    Directory of Open Access Journals (Sweden)

    Yoshimi Kazuto

    2012-10-01

    Full Text Available Abstract Background Chemotherapeutic bioassay for colorectal cancer (CRC with a rat model bearing chemically-induced CRCs plays an important role in the development of new anti-tumor drugs and regimens. Although several protocols to induce CRCs have been developed, the incidence and number of CRCs are not much enough for the efficient bioassay. Recently, we established the very efficient system to induce CRCs with a chemically induced-colon carcinogenesis-prone Apc-mutant rat, Kyoto Apc Delta (KAD rat. Here, we applied the KAD rat to the chemotherapeutic bioassay for CRC and showed the utility of the KAD rat. Methods The KAD rat has been developed by the ENU mutagenesis and carries a homozygous nonsense mutation in the Apc gene (S2523X. Male KAD rats were given a single subcutaneous injection of AOM (20 mg/kg body weight at 5 weeks of age. Starting at 1 week after the AOM injection, they were given 2% DSS in drinking water for 7 days. Tumor-bearing KAD rats were divided into experimental and control groups on the basis of the number of tumors observed by endoscopy at week 8. The 5-fluorouracil (5-FU was administrated intravenously a dose of 50 or 75 mg/kg weekly at week 9, 10, and 11. After one-week interval, the 5-FU was given again at week 13, 14, and 15. At week 16, animals were sacrificed and tumor number and volume were measured macroscopically and microscopically. Results In total 48 tumors were observed in 27 KAD rats with a 100% incidence at week 8. The maximum tolerated dose for the KAD rat was 50 mg/kg of 5-FU. Macroscopically, the number or volume of tumors in the 5-FU treated rats was not significantly different from the control. Microscopically, the number of adenocarcinoma in the 5-FU treated rats was not significantly different (p Conclusion The use of the AOM/DSS-treated tumor-bearing KAD rats could shorten the experimental period and reduce the number of animals examined in the chemotherapeutic bioassay. The

  4. Gallstones and colorectal cancer

    DEFF Research Database (Denmark)

    Jørgensen, Torben; Rafaelsen, Søren Rafael

    1992-01-01

    The prevalence of gallstone disease in 145 consecutive patients with colorectal cancer was compared with gallstone prevalence in 4,159 subjects randomly selected from a population. The group of patients had a significantly higher prevalence of gallstone disease than the population (odds ratio = 1.......59; 95 percent confidence limits 1.04-2.45), whereas cholecystectomies occurred with equal frequency in the two groups. There was a nonsignificant trend toward more right-sided cancers in patients with gallstones than in patients without. These results, together with available literature, give...... substantial evidence for an association between gallstones and colorectal cancer, an association which is not due to cholecystectomy being a predisposing factor to colorectal cancer. Sporadic findings of an association between cholecystectomy and colorectal cancer can be explained by the above relationship....

  5. Hereditary colorectal cancer diagnostics

    DEFF Research Database (Denmark)

    Klarskov, Louise; Holck, Susanne; Bernstein, Inge

    2012-01-01

    BackgroundThe hereditary non-polyposis colorectal cancer (HNPCC) subset of tumours can broadly be divided into tumours caused by an underlying mismatch-repair gene mutation, referred to as Lynch syndrome, and those that develop in families with similar patterns of heredity but without disease......-predisposing germline mismatch repair mutations, referred to as familial colorectal cancer type X (FCCTX). Recognition of HNPCC-associated colorectal cancers is central since surveillance programmes effectively reduce morbidity and mortality. The characteristic morphological features linked to Lynch syndrome can aid...... in the identification of this subset, whereas the possibility to use morphological features as an indicator of FCCTX is uncertain.Objective and methodsTo perform a detailed morphological evaluation of HNPCC-associated colorectal cancers and demonstrate significant differences between tumours associated with FCCTX...

  6. Prophylaxis against colorectal cancer

    DEFF Research Database (Denmark)

    Bülow, Steffen; Kronborg, O

    1996-01-01

    Colorectal cancer is diagnosed in more than 3000 people every year in Denmark, with a population of 5 million, and 2000 die from this disease every year. The aetiology of the disease is complex, but an increasing number of cancers have been related to genetics and Denmark is contributing...... with a well-established register of familial adenomatous polyposis and a recently founded register for hereditary nonpolyposis colorectal cancer, both with major international relationships. The Danish tradition of epidemiology and clinical trials has also been demonstrated in population screening trials...... for colorectal cancer in average-risk persons as well as high-risk groups with precursors of the disease. The present review places Danish contributions within the prophylaxis of colorectal cancer during the last decade in an international context....

  7. Alcohol metabolism: role in toxicity and carcinogenesis.

    Science.gov (United States)

    Badger, Thomas M; Ronis, Martin J J; Seitz, Helmut K; Albano, Emanuele; Ingelman-Sundberg, Magnus; Lieber, Charles S

    2003-02-01

    This article contains the proceedings of a symposium at the 2002 RSA Meeting in San Francisco, organized and co-chaired by Thomas M. Badger, Paul Shih-Jiun Yin, and Helmut Seitz. The presentations were (1) First-pass metabolism of ethanol: Basic and clinical aspects, by Charles Lieber; (2) Intracellular CYP2E1 transport, oxidative stress, cytokine release, and ALD, by Magnus Ingelman-Sundberg; (3) Pulsatile ethanol metabolism in intragastric infusion models: Potential role in toxic outcomes, by Thomas M. Badger and Martin J.J. Ronis; (4) Free radicals, adducts, and autoantibodies resulting from ethanol metabolism: Role in ethanol-associated toxicity, by Emanuele Albano; and (5) Gastrointestinal metabolism of ethanol and its possible role in carcinogenesis, by Helmut Seitz.

  8. Role of retinoic receptors in lung carcinogenesis

    Directory of Open Access Journals (Sweden)

    Renyi-Vamos Ferenc

    2008-07-01

    Full Text Available Abstract Several in vitro and in vivo studies have examined the positive and negative effects of retinoids (vitamin A analogs in premalignant and malignant lesions. Retinoids have been used as chemopreventive and anticancer agents because of their pleiotropic regulator function in cell differentiation, growth, proliferation and apoptosis through interaction with two types of nuclear receptors: retinoic acid receptors and retinoid X receptors. Recent investigations have gradually elucidated the function of retinoids and their signaling pathways and may explain the failure of earlier chemopreventive studies. In this review we have compiled basic and recent knowledge regarding the role of retinoid receptors in lung carcinogenesis. Sensitive and appropriate biological tools are necessary for screening the risk population and monitoring the efficacy of chemoprevention. Investigation of retinoid receptors is important and may contribute to the establishment of new strategies in chemoprevention for high-risk patients and in the treatment of lung cancer.

  9. (Radiation carcinogenesis in the whole body system)

    Energy Technology Data Exchange (ETDEWEB)

    Fry, R.J.M.

    1990-12-14

    The objectives of the trip were: to take part in and to give the summary of a Symposium on Radiation Carcinogenesis at Tokyo, and to give a talk at the National Institute of Radiological Sciences at Chiba. The breadth of the aspects considered at the conference was about as broad as is possible, from effects at the molecular level to human epidemiology, from the effects of tritium to cancer induction by heavy ions. The events induced by cancer that lead to cancer and the events that are secondary are beginning to come into better focus but much is still not known. Interest in suppressor genes is increasing rapidly in the studies of human tumors and many would predict that the three or four suppressor genes associated with cancer are only the first sighting of a much larger number.

  10. Spatial Measures of Genetic Heterogeneity During Carcinogenesis.

    Science.gov (United States)

    Storey, K; Ryser, M D; Leder, K; Foo, J

    2017-02-01

    In this work we explore the temporal dynamics of spatial heterogeneity during the process of tumorigenesis from healthy tissue. We utilize a spatial stochastic model of mutation accumulation and clonal expansion in a structured tissue to describe this process. Under a two-step tumorigenesis model, we first derive estimates of a non-spatial measure of diversity: Simpson's Index, which is the probability that two individuals sampled at random from the population are identical, in the premalignant population. We next analyze two new measures of spatial population heterogeneity. In particular we study the typical length scale of genetic heterogeneity during the carcinogenesis process and estimate the extent of a surrounding premalignant clone given a clinical observation of a premalignant point biopsy. This evolutionary framework contributes to a growing literature focused on developing a better understanding of the spatial population dynamics of cancer initiation and progression.

  11. Colorectal polyps in childhood.

    Science.gov (United States)

    Thakkar, Kalpesh; Fishman, Douglas S; Gilger, Mark A

    2012-10-01

    Colorectal polyps are a common cause of gastrointestinal bleeding in children. This review updates the information on colorectal polyps and summarizes the recent advances in genetics, diagnosis, and treatment of polyps in the large intestine. A review of recent literature regarding colorectal polyps demonstrates an estimated detected prevalence of 6.1% overall and 12.0% among those with lower gastrointestinal bleeding during pediatric colonoscopy. Non-Caucasian races (e.g., black and Hispanic) are at higher risk for colorectal polyps in childhood. Recent data show juvenile polyps may recur in approximately 45% of children with multiple polyps and 17% of children with solitary polyps. A clinical trial showed that celecoxib, a cyclooxygenase (COX)-2 inhibitor, significantly reduced the number of colorectal polyps in children with familial adenomatous polyposis (FAP). Ethical challenges related to genetic tests for FAP have been newly examined. The utility of novel endoscopic techniques (e.g., enteroscopy) in Peutz-Jeghers Syndrome to prevent intussusception have been newly described. Although colorectal polyps in children are generally benign and easily removed, careful clinical evaluation and ongoing research are needed to identify the small proportion of children at risk for cancer. The current paradigm of using the polyp number at presentation as a primary determinant of subsequent surveillance may be inadequate for many patients.

  12. DNA methylation patterns in blood of patients with colorectal cancer and adenomatous colorectal polyps.

    Science.gov (United States)

    Cassinotti, Elisa; Melson, Joshua; Liggett, Thomas; Melnikov, Anatoliy; Yi, Qilong; Replogle, Charles; Mobarhan, Sohrab; Boni, Luigi; Segato, Sergio; Levenson, Victor

    2012-09-01

    Colorectal cancer (CRC) screening rates are currently suboptimal. Blood-based screening could improve rates of earlier detection for CRC and adenomatous colorectal polyps. In this study, we evaluated the feasibility of plasma-based detection of early CRC and adenomatous polyps using array-mediated analysis methylation profiling of 56 genes implicated in carcinogenesis. Methylation of 56 genes in patients with Stages I and II CRC (N=30) and those with adenomatous polyps (N=30) were compared with individuals who underwent colonoscopy and were found to have neither adenomatous changes nor CRC. Composite biomarkers were developed for adenomatous polyps and CRC, and their sensitivity and specificity was estimated using five-fold cross validation. Six promoters (CYCD2, HIC1, PAX 5, RASSF1A, RB1 and SRBC) were selected for the biomarker, which differentiated CRC patients and controls with 84% sensitivity and 68% specificity. Three promoters (HIC1, MDG1 and RASSF1A) were selected for the biomarker, which differentiated patients with adenomatous polyps and controls with sensitivity of 55% and specificity of 65%. Methylation profiling of plasma DNA can detect early CRC with significant accuracy and shows promise as a methodology to develop biomarkers for CRC screening. Copyright © 2011 UICC.

  13. Is peritoneal reflection the best anatomical repair landmark in experimental colorectal surgery on rats? A reflexão peritoneal é o melhor reparo anatômico na cirurgia experimental colorretal em ratos?

    Directory of Open Access Journals (Sweden)

    Denise Gonçalves Priolli

    2009-12-01

    Full Text Available PURPOSE: To validate Peyer's patch as an anatomical repair landmark for colorectal surgery in rats and to measure the collagen content in segments of the colon containing or not containing Peyer's patch. METHODS: The distance between Peyer's patch and the peritoneal reflection was measured in forty-five Wistar rats. The colon and rectum were resected for quantification of collagen content by means of computer-assisted image analysis in regions of the colon with and without Peyer's patch. RESULTS: There was great variation in the distance between Peyer's patch and the peritoneal reflection when the male and female rats were considered as a single group (p=0.04. Comparison between the genders showed that the distance between the patch and the peritoneal reflection was greater in female than in male rats (p=0.001. The colonic segment containing Peyer's patch was observed to have lower tissue collagen content than the segment in which this structure was not present (p=0.02. CONCLUSION: Peyer's patch can be indicated as an anatomical repair landmark, and there is a need to study the healing of colorectal anastomoses in rats based on differing quantities of tissue collagen existing in the colonic wall with or without this structure.OBJETIVO: Validar a placa de Peyer como reparo anatômico para a cirurgia colorretal em ratos e mensurar a quantidade de colágeno em segmentos da parede cólica que contém ou não a placa de Peyer. MÉTODOS: Foi aferida a distância entre a placa de Peyer e a reflexão peritoneal em 45 ratos Wistar. O cólon e o reto foram ressecados, para a quantificação do colágeno, por meio de análise de imagem assistida por computador, em regiões do cólon que continham ou não a placa de Peyer. RESULTADOS: Existe grande variação entre a distância da placa de Peyer e a reflexão peritoneal quando se consideraram os animais de ambos os gêneros como grupo único (p= 0.04, sendo a distância entre a placa e a reflex

  14. Colorectal Carcinoma: A General Overview and Future Perspectives in Colorectal Cancer

    Directory of Open Access Journals (Sweden)

    Inés Mármol

    2017-01-01

    Full Text Available Colorectal cancer (CRC is the third most common cancer and the fourth most common cause of cancer-related death. Most cases of CRC are detected in Western countries, with its incidence increasing year by year. The probability of suffering from colorectal cancer is about 4%–5% and the risk for developing CRC is associated with personal features or habits such as age, chronic disease history and lifestyle. In this context, the gut microbiota has a relevant role, and dysbiosis situations can induce colonic carcinogenesis through a chronic inflammation mechanism. Some of the bacteria responsible for this multiphase process include Fusobacterium spp, Bacteroides fragilis and enteropathogenic Escherichia coli. CRC is caused by mutations that target oncogenes, tumour suppressor genes and genes related to DNA repair mechanisms. Depending on the origin of the mutation, colorectal carcinomas can be classified as sporadic (70%; inherited (5% and familial (25%. The pathogenic mechanisms leading to this situation can be included in three types, namely chromosomal instability (CIN, microsatellite instability (MSI and CpG island methylator phenotype (CIMP. Within these types of CRC, common mutations, chromosomal changes and translocations have been reported to affect important pathways (WNT, MAPK/PI3K, TGF-β, TP53, and mutations; in particular, genes such as c-MYC, KRAS, BRAF, PIK3CA, PTEN, SMAD2 and SMAD4 can be used as predictive markers for patient outcome. In addition to gene mutations, alterations in ncRNAs, such as lncRNA or miRNA, can also contribute to different steps of the carcinogenesis process and have a predictive value when used as biomarkers. In consequence, different panels of genes and mRNA are being developed to improve prognosis and treatment selection. The choice of first-line treatment in CRC follows a multimodal approach based on tumour-related characteristics and usually comprises surgical resection followed by chemotherapy combined

  15. Colorectal Carcinoma: A General Overview and Future Perspectives in Colorectal Cancer.

    Science.gov (United States)

    Mármol, Inés; Sánchez-de-Diego, Cristina; Pradilla Dieste, Alberto; Cerrada, Elena; Rodriguez Yoldi, María Jesús

    2017-01-19

    Colorectal cancer (CRC) is the third most common cancer and the fourth most common cause of cancer-related death. Most cases of CRC are detected in Western countries, with its incidence increasing year by year. The probability of suffering from colorectal cancer is about 4%-5% and the risk for developing CRC is associated with personal features or habits such as age, chronic disease history and lifestyle. In this context, the gut microbiota has a relevant role, and dysbiosis situations can induce colonic carcinogenesis through a chronic inflammation mechanism. Some of the bacteria responsible for this multiphase process include Fusobacterium spp, Bacteroides fragilis and enteropathogenic Escherichia coli . CRC is caused by mutations that target oncogenes, tumour suppressor genes and genes related to DNA repair mechanisms. Depending on the origin of the mutation, colorectal carcinomas can be classified as sporadic (70%); inherited (5%) and familial (25%). The pathogenic mechanisms leading to this situation can be included in three types, namely chromosomal instability (CIN), microsatellite instability (MSI) and CpG island methylator phenotype (CIMP). Within these types of CRC, common mutations, chromosomal changes and translocations have been reported to affect important pathways (WNT, MAPK/PI3K, TGF-β, TP53), and mutations; in particular, genes such as c-MYC, KRAS , BRAF , PIK3CA , PTEN , SMAD2 and SMAD4 can be used as predictive markers for patient outcome. In addition to gene mutations, alterations in ncRNAs, such as lncRNA or miRNA, can also contribute to different steps of the carcinogenesis process and have a predictive value when used as biomarkers. In consequence, different panels of genes and mRNA are being developed to improve prognosis and treatment selection. The choice of first-line treatment in CRC follows a multimodal approach based on tumour-related characteristics and usually comprises surgical resection followed by chemotherapy combined with

  16. Reduced expression of EphA5 is associated with lymph node metastasis, advanced TNM stage, and poor prognosis in colorectal carcinoma.

    Science.gov (United States)

    Gu, Shudong; Feng, Jia; Jin, Qin; Wang, Wei; Zhang, Shu

    2017-05-01

    Colorectal carcinoma (CRC) is the third most common cancer and a major cause of morbidity and mortality throughout the world. The prognosis of patients has improved markedly over the last 15 years because of the introduction of new therapy including molecular target drugs. To comprehensively understand the molecular process of carcinogenesis of colorectal carcinoma is essential for the diagnosis, prognosis and treatment. EphA5 is a member of the Eph family and plays a critical role in carcinogenesis of lung cancer, prostate cancer, and breast cancer. The expression profile and the role of EphA5 in colorectal carcinoma have not been well investigated till now. In this study, a set of colorectal carcinoma specimens was subjected to immunohistochemical assay using an EphA5 specific antibody. The relationship between the expression of EphA5 and clinicopathological parameters was statistically analyzed. EphA5 was positively expressed in all tested normal mucosa specimens (120/120, 100%) and partly in colorectal carcinoma specimens (70/120, 58.3%). The loss of EphA5 protein was associated with depth of wall invasion (P=0.002), poor tumor differentiation (Pcarcinoma and it may be a new therapeutic target for colorectal carcinoma.

  17. 6 Common Cancers - Colorectal Cancer

    Science.gov (United States)

    ... Home Current Issue Past Issues 6 Common Cancers - Colorectal Cancer Past Issues / Spring 2007 Table of Contents For ... of colon cancer. Photo: AP Photo/Ron Edmonds Colorectal Cancer Cancer of the colon (large intestine) or rectum ( ...

  18. Developments in Colorectal Cancer Screening

    Science.gov (United States)

    ... JavaScript on. Feature: Colorectal Cancer Developments in Colorectal Cancer Screening Past Issues / Summer 2016 Table of Contents Dr. ... patients know to help determine the best colon cancer screening test for them? Colonoscopy is considered the gold ...

  19. Dietary fiber intake and risk of colorectal cancer and incident and recurrent adenoma in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial12

    Science.gov (United States)

    Kunzmann, Andrew T; Coleman, Helen G; Huang, Wen-Yi; Kitahara, Cari M; Cantwell, Marie M; Berndt, Sonja I

    2015-01-01

    distal colon cancer and that this effect of dietary fiber, particularly from cereals and fruit, may begin early in colorectal carcinogenesis. This trial was registered at clinicaltrials.gov as NCT01696981. PMID:26269366

  20. Dietary fiber intake and risk of colorectal cancer and incident and recurrent adenoma in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial.

    Science.gov (United States)

    Kunzmann, Andrew T; Coleman, Helen G; Huang, Wen-Yi; Kitahara, Cari M; Cantwell, Marie M; Berndt, Sonja I

    2015-10-01

    fiber, particularly from cereals and fruit, may begin early in colorectal carcinogenesis. This trial was registered at clinicaltrials.gov as NCT01696981. © 2015 American Society for Nutrition.

  1. Lactoferrin Deficiency Promotes Colitis-Associated Colorectal Dysplasia in Mice

    Science.gov (United States)

    Ye, Qiurong; Zheng, Ying; Fan, Songqing; Qin, Zailong; Li, Nan; Tang, Anliu; Ai, Feiyan; Zhang, Xuemei; Bian, Yanhui; Dang, Wei; Huang, Jing; Zhou, Ming; Zhou, Yanhong; Xiong, Wei; Yan, Qun; Ma, Jian; Li, Guiyuan

    2014-01-01

    Nonresolving inflammatory processes affect all stages of carcinogenesis. Lactoferrin, a member of the transferrin family, is involved in the innate immune response and anti-inflammatory, anti-microbial, and anti-tumor activities. We previously found that lactoferrin is significantly down-regulated in specimens of nasopharyngeal carcinoma (NPC) and negatively associated with tumor progression, metastasis, and prognosis of patients with NPC. Additionally, lactoferrin expression levels are decreased in colorectal cancer as compared with normal tissue. Lactoferrin levels are also increased in the various phases of inflammation and dysplasia in an azoxymethane–dextran sulfate sodium (AOM-DSS) model of colitis-associated colon cancer (CAC). We thus hypothesized that the anti-inflammatory function of lactoferrin may contribute to its anti-tumor activity. Here we generated a new Lactoferrin knockout mouse model in which the mice are fertile, develop normally, and display no gross morphological abnormalities. We then challenged these mice with chemically induced intestinal inflammation to investigate the role of lactoferrin in inflammation and cancer development. Lactoferrin knockout mice demonstrated a great susceptibility to inflammation-induced colorectal dysplasia, and this characteristic may be related to inhibition of NF-κB and AKT/mTOR signaling as well as regulation of cell apoptosis and proliferation. Our results suggest that the protective roles of lactoferrin in colorectal mucosal immunity and inflammation-related malignant transformation, along with a deficiency in certain components of the innate immune system, may lead to serious consequences under conditions of inflammatory insult. PMID:25057912

  2. Colorectal Cancer Risk Assessment Tool

    Science.gov (United States)

    ... know before using this tool: The Colorectal Cancer Risk Assessment Tool was designed for use by doctors and other health providers with their patients. If you are not a health ... your personal risk of colorectal cancer. (Colorectal cancer is another way ...

  3. Colorectal Cancer: A Personal Journey

    Science.gov (United States)

    ... be as fortunate as we are.” Reflecting what research has proven, Valvo’s message is clear. “Screening is so important! Early detection is early cure!” Read More "Colorectal Cancer" Articles Colorectal Cancer: A Personal Journey / The Importance of Early Detection / Developments in Colorectal ...

  4. Detouring the Undesired Route of Helicobacter pylori-Induced Gastric Carcinogenesis

    Directory of Open Access Journals (Sweden)

    Ki Baik Hahm

    2011-07-01

    Full Text Available Epidemiological and experimental evidence has emerged that a dysregulated inflammation is associated with most of the tumors, and many studies have begun to unravel the molecular pathways linking inflammation and cancer. As a typical example linking these associations, Helicobacter pylori (H. pylori infection-associated atrophic gastritis has been recognized as precursor lesion of gastric cancer. The identification of transcription factors such as NF-κB and STAT3, and their gene products such as IL-8, COX-2, iNOS, cytokines, chemokines and their receptors, etc have laid the molecular foundation for our understanding of the decisive role of inflammation in carcinogenesis. In addition to the role as the initiator of cancer, inflammation contributes to survival and proliferation of malignant cells, tumor angiogenesis, and even metastasis. In this review, the fundamental mechanisms of H. pylori-induced carcinogenesis as well as the possibility of cancer prevention through suppressing H. pylori-induced inflammation are introduced. We infer that targeting inflammatory pathways have a potential role to detour the unpleasant journey to H. pylori-associated gastric carcinogenesis.

  5. Detouring the Undesired Route of Helicobacter pylori-Induced Gastric Carcinogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Eun-Hee; Hong, Kyung-Sook; Hong, Hua [Lab of Translational Medicine, Lee Gil Ya Cancer and Diabetes Institute, Gachon University of Medicine and Science, 7-45 Songdo-dong, Yeonsu-gu, Incheon 406-840 (Korea, Republic of); Hahm, Ki Baik, E-mail: hahmkb@gachon.ac.kr [Lab of Translational Medicine, Lee Gil Ya Cancer and Diabetes Institute, Gachon University of Medicine and Science, 7-45 Songdo-dong, Yeonsu-gu, Incheon 406-840 (Korea, Republic of); Department of Gastroenterology, Gachon Graduate School of Medicine, Gil Hospital, Incheon 406-840 (Korea, Republic of)

    2011-07-25

    Epidemiological and experimental evidence has emerged that a dysregulated inflammation is associated with most of the tumors, and many studies have begun to unravel the molecular pathways linking inflammation and cancer. As a typical example linking these associations, Helicobacter pylori (H. pylori) infection-associated atrophic gastritis has been recognized as precursor lesion of gastric cancer. The identification of transcription factors such as NF-κB and STAT3, and their gene products such as IL-8, COX-2, iNOS, cytokines, chemokines and their receptors, etc have laid the molecular foundation for our understanding of the decisive role of inflammation in carcinogenesis. In addition to the role as the initiator of cancer, inflammation contributes to survival and proliferation of malignant cells, tumor angiogenesis, and even metastasis. In this review, the fundamental mechanisms of H. pylori-induced carcinogenesis as well as the possibility of cancer prevention through suppressing H. pylori-induced inflammation are introduced. We infer that targeting inflammatory pathways have a potential role to detour the unpleasant journey to H. pylori-associated gastric carcinogenesis.

  6. Tumor Necrosis Factor-α is Associated with Positive Lymph Node Status in Patients with Recurrence of Colorectal Cancer – Indications for Anti-TNF-α Agents in Cancer Treatment

    Directory of Open Access Journals (Sweden)

    M. Grimm

    2010-01-01

    Full Text Available Introduction: The progressive growth of malignancies is accompanied by a decline in the immune response through mechanisms which are poorly understood. Apoptosis and induction of inflammation by tumor released cytokines as tumor escape mechanisms have been proposed to play an important role in colorectal carcinogenesis.

  7. Cellular metabolism in colorectal carcinogenesis: Influence of lifestyle, gut microbiome and metabolic pathways.

    Science.gov (United States)

    Hagland, Hanne R; Søreide, Kjetil

    2015-01-28

    The interconnectivity between diet, gut microbiota and cell molecular responses is well known; however, only recently has technology allowed the identification of strains of microorganisms harbored in the gastrointestinal tract that may increase susceptibility to cancer. The colonic environment appears to play a role in the development of colon cancer, which is influenced by the human metabolic lifestyle and changes in the gut microbiome. Studying metabolic changes at the cellular level in cancer be useful for developing novel improved preventative measures, such as screening through metabolic breath-tests or treatment options that directly affect the metabolic pathways responsible for the carcinogenicity. Copyright © 2014 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

  8. Microsatellite Instability Markers Status in Colorectal Cancer

    Directory of Open Access Journals (Sweden)

    Giti Esmailnia

    2014-12-01

    Full Text Available Background: Colorectal cancer (CRC is the third most prevalent and the third leading cause of cancer-related deaths in Iran. Our aim was to investigate five mononucleotide statuses among Iranian patients with sporadic colorectal cancer. Materials and Methods: In this experimental study 80 sporadic CRC patients were evaluated for microsatellite instability (MSI. The pentaplex panel including 5 quasi mononucleotide microsatellite markers (NR-21, BAT-26, BAT-25, NR-27 and NR-24 was used. The MSI analysis was performed on paired tumoral DNA from cancerous tissues and genomic DNA from whole blood. MSI carriers were identified by analysis of tumor tissue using polymerase chain reaction. Results: Our findings showed that microsatellite instability was detected in 36 of 80 cases (45% with colorectal cancer. MSI analysis revealed that 17 cases of MSI-H (21%, 19 MSI-L (23% and 44 microsatellite stable tumors (55%. Instability is observed in the tumoral DNA compared to the DNA from the normal DNA sample. The most instable markers were NR-21, NR-24 in which instability was detected in 45% of patients. Conclusion: Using a panel including 3 mentioned MSI markers should be more promising markers for identifying MSI status in patients with sporadic colorectal cancer.

  9. Effect of Dendrobium officinale Extraction on Gastric Carcinogenesis in Rats

    Directory of Open Access Journals (Sweden)

    Yi Zhao

    2016-01-01

    Full Text Available Dendrobium officinale (Tie Pi Shi Hu in Chinese has been widely used to treat different diseases in China. Anticancer effect is one of the important effects of Dendrobium officinale. However, the molecular mechanism of its anticancer effect remains unclear. In the present study, gastric carcinogenesis in rats was used to evaluate the effect of Dendrobium officinale on cancer, and its pharmacological mechanism was explored. Dendrobium officinale extracts (4.8 and 2.4 g/kg were orally administered to the rats of the gastric carcinogenesis model. Compared with the cancer model group, the high dose of Dendrobium officinale extracts significantly inhibited the rate of carcinogenesis. Further analysis revealed that Dendrobium officinale extracts could regulate the DNA damage, oxidative stress, and cytokines related with carcinogenesis and induce cell apoptosis in order to prevent gastric cancer.

  10. Effect of Dendrobium officinale Extraction on Gastric Carcinogenesis in Rats

    Science.gov (United States)

    Liu, Yan; Lan, Xi-Ming; Xu, Guo-Liang; Sun, You-Zhi; Li, Fei

    2016-01-01

    Dendrobium officinale (Tie Pi Shi Hu in Chinese) has been widely used to treat different diseases in China. Anticancer effect is one of the important effects of Dendrobium officinale. However, the molecular mechanism of its anticancer effect remains unclear. In the present study, gastric carcinogenesis in rats was used to evaluate the effect of Dendrobium officinale on cancer, and its pharmacological mechanism was explored. Dendrobium officinale extracts (4.8 and 2.4 g/kg) were orally administered to the rats of the gastric carcinogenesis model. Compared with the cancer model group, the high dose of Dendrobium officinale extracts significantly inhibited the rate of carcinogenesis. Further analysis revealed that Dendrobium officinale extracts could regulate the DNA damage, oxidative stress, and cytokines related with carcinogenesis and induce cell apoptosis in order to prevent gastric cancer. PMID:28119756

  11. Chemopreventive activity of grape juice concentrate (G8000TM) on rat colon carcinogenesis induced by azoxymethane.

    Science.gov (United States)

    Silva, Roseane Mendes; Campanholo, Vanessa Maria de Lima Pazine; Paiotti, Ana Paula Ribeiro; Artigiani Neto, Ricardo; Oshima, Celina Tizuko Fujiyama; Ribeiro, Daniel Araki; Forones, Nora Manoukian

    2015-11-01

    Colorectal cancer is the third most common cancer worldwide in both sexes, with similar geographic patterns between genders. This neoplasm has good prognosis if the disease is diagnosed at early stages. The aim of this study was to evaluate the effect of red grape juice on the expression of COX-2 and Ki-67 expression following colon carcinogenesis induced by azoxymethane (AOM). Thirty-five rats were randomly distributed into seven groups (n=5 per group): G1: SHAM or negative control received only saline; G2 (positive control): animals received 15 mg/kg AOM; G3: animals received 1% red grape juice 2 weeks before the administration of AOM; G4: animals received 2% red grape juice 2 weeks before the administration of AOM; G5: animals received 1% red grape juice 4 weeks after the last administration of AOM; G6: animals received 2% red grape juice 4 weeks after the last administration of AOM; G7: animals received only 2% red grape juice. COX-2 mRNA expression was reduced in animals treated with 1% red grape juice before AOM induction or 2% red grape juice after AOM induction. COX-2 immunoexpression was also reduced to groups treated with red grape juice at 1% before and after AOM induction or 2% red grape juice after AOM induction. Decreased immunoexpression of Ki-67 positive cells was observed in animals treated with 1% grape juice before AOM-treated animals. Taken together, grape juice concentrate is able to exert some chemopreventive activity on rat colon carcinogenesis. Copyright © 2015 Elsevier B.V. All rights reserved.

  12. Primary prevention of colorectal cancer: are we closer to reality?

    LENUS (Irish Health Repository)

    Qasim, Asghar

    2012-02-01

    Colorectal cancer is one of the leading causes of morbidity and mortality worldwide. An early detection of colorectal cancer determines therapeutic outcomes, while primary prevention remains a challenge. Our aim was to review the dietary, geographical and genetic factors in the causation and their possible role in the primary prevention of colorectal cancer. Data from experimental and clinical studies and population screening programmes were analysed to determine the factors responsible for causation of colorectal cancer. The role of dietary constituents, including the consumption of fat, red meat, fibre content, alcohol consumption, and other lifestyle issues, including obesity, lack of exercise and geographical variations in cancer prevalence were reviewed. The role of genetic and lifestyle factors in causation of colorectal cancer is evident from the experimental, clinical and population-based studies. Dietary factors, including the consumption of fat, fibre, red meat and alcohol, seem to have a significant influence in this regard. The role of micronutrients, vitamins, calcium may be relevant but remain largely unclear. In conclusion, there is ample evidence favouring the role of various dietary and lifestyle factors in the aetiology of colorectal cancer. Modification of these factors is an attractive option, which is likely to help in the primary prevention and reduced disease burden.

  13. Exocrine pancreatic carcinogenesis and autotaxin expression.

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    Sandeep Kadekar

    Full Text Available Exocrine pancreatic cancer is an aggressive disease with an exceptionally high mortality rate. Genetic analysis suggests a causative role for environmental factors, but consistent epidemiological support is scarce and no biomarkers for monitoring the effects of chemical pancreatic carcinogens are available. With the objective to identify common traits for chemicals inducing pancreatic tumors we studied the National Toxicology Program (NTP bioassay database. We found that male rats were affected more often than female rats and identified eight chemicals that induced exocrine pancreatic tumors in males only. For a hypothesis generating process we used a text mining tool to analyse published literature for suggested mode of actions (MOA. The resulting MOA analysis suggested inflammatory responses as common feature. In cell studies we found that all the chemicals increased protein levels of the inflammatory protein autotaxin (ATX in Panc-1, MIA PaCa-2 or Capan-2 cells. Induction of MMP-9 and increased invasive migration were also frequent effects, consistent with ATX activation. Testosterone has previously been implicated in pancreatic carcinogenesis and we found that it increased ATX levels. Our data show that ATX is a target for chemicals inducing pancreatic tumors in rats. Several lines of evidence implicate ATX and its product lysophosphatidic acid in human pancreatic cancer. Mechanisms of action may include stimulated invasive growth and metastasis. ATX may interact with hormones or onco- or suppressor-genes often deregulated in exocrine pancreatic cancer. Our data suggest that ATX is a target for chemicals promoting pancreatic tumor development.

  14. Somatic Host Cell Alterations in HPV Carcinogenesis

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    Tamara R. Litwin

    2017-08-01

    Full Text Available High-risk human papilloma virus (HPV infections cause cancers in different organ sites, most commonly cervical and head and neck cancers. While carcinogenesis is initiated by two viral oncoproteins, E6 and E7, increasing evidence shows the importance of specific somatic events in host cells for malignant transformation. HPV-driven cancers share characteristic somatic changes, including apolipoprotein B mRNA editing catalytic polypeptide-like (APOBEC-driven mutations and genomic instability leading to copy number variations and large chromosomal rearrangements. HPV-associated cancers have recurrent somatic mutations in phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA and phosphatase and tensin homolog (PTEN, human leukocyte antigen A and B (HLA-A and HLA-B-A/B, and the transforming growth factor beta (TGFβ pathway, and rarely have mutations in the tumor protein p53 (TP53 and RB transcriptional corepressor 1 (RB1 tumor suppressor genes. There are some variations by tumor site, such as NOTCH1 mutations which are primarily found in head and neck cancers. Understanding the somatic events following HPV infection and persistence can aid the development of early detection biomarkers, particularly when mutations in precancers are characterized. Somatic mutations may also influence prognosis and treatment decisions.

  15. Somatic Host Cell Alterations in HPV Carcinogenesis.

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    Litwin, Tamara R; Clarke, Megan A; Dean, Michael; Wentzensen, Nicolas

    2017-08-03

    High-risk human papilloma virus (HPV) infections cause cancers in different organ sites, most commonly cervical and head and neck cancers. While carcinogenesis is initiated by two viral oncoproteins, E6 and E7, increasing evidence shows the importance of specific somatic events in host cells for malignant transformation. HPV-driven cancers share characteristic somatic changes, including apolipoprotein B mRNA editing catalytic polypeptide-like (APOBEC)-driven mutations and genomic instability leading to copy number variations and large chromosomal rearrangements. HPV-associated cancers have recurrent somatic mutations in phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha ( PIK3CA ) and phosphatase and tensin homolog ( PTEN ), human leukocyte antigen A and B ( HLA-A and HLA-B ) -A/B , and the transforming growth factor beta (TGFβ) pathway, and rarely have mutations in the tumor protein p53 ( TP53 ) and RB transcriptional corepressor 1 ( RB1 ) tumor suppressor genes. There are some variations by tumor site, such as NOTCH1 mutations which are primarily found in head and neck cancers. Understanding the somatic events following HPV infection and persistence can aid the development of early detection biomarkers, particularly when mutations in precancers are characterized. Somatic mutations may also influence prognosis and treatment decisions.

  16. Carcinogenesis induced by low-dose radiation

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    Piotrowski Igor

    2017-11-01

    Full Text Available Although the effects of high dose radiation on human cells and tissues are relatively well defined, there is no consensus regarding the effects of low and very low radiation doses on the organism. Ionizing radiation has been shown to induce gene mutations and chromosome aberrations which are known to be involved in the process of carcinogenesis. The induction of secondary cancers is a challenging long-term side effect in oncologic patients treated with radiation. Medical sources of radiation like intensity modulated radiotherapy used in cancer treatment and computed tomography used in diagnostics, deliver very low doses of radiation to large volumes of healthy tissue, which might contribute to increased cancer rates in long surviving patients and in the general population. Research shows that because of the phenomena characteristic for low dose radiation the risk of cancer induction from exposure of healthy tissues to low dose radiation can be greater than the risk calculated from linear no-threshold model. Epidemiological data collected from radiation workers and atomic bomb survivors confirms that exposure to low dose radiation can contribute to increased cancer risk and also that the risk might correlate with the age at exposure.

  17. DNA repair, damage signaling and carcinogenesis.

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    Lavelle, Christophe; Salles, Bernard; Wiesmüller, Lisa

    2008-04-02

    The First joint meeting of the German DGDR (German Society for Research on DNA Repair) and the French SFTG (French Society of Genotoxicology) on DNA Repair was held in Toulouse, France, from September 15 to 19, 2007. It was organized by Lisa Wiesmüller and Bernard Salles together with the scientific committee consisting of Gilbert de Murcia, Jean-Marc Egly, Frank Grosse, Karl-Peter Hopfner, Georges Iliakis, Bernd Kaina, Markus Löbrich, Bernard Lopez, Daniel Marzin and Alain Sarasin. This report summarizes information presented by the speakers (invited lectures and oral communications) during the seven plenary sessions, which include (1) excision repair, (2) DNA repair and carcinogenesis, (3) double-strand break repair, (4) replication in repair and lesion bypass, (5) cellular responses to genotoxic stress, (6) DNA repair machinery within the chromatin context and (7) genotoxicology and testing. A total of 23 plenary lectures, 32 oral communications and 66 posters were presented in this rather intense 4 days meeting, which stimulated extensive discussions and highly interdisciplinary scientific exchanges among the approximately 250 participants.

  18. Theories of endometrial carcinogenesis: a multidisciplinary approach.

    Science.gov (United States)

    Sherman, M E

    2000-03-01

    Historical observations have suggested that endometrial carcinomas vary in histopathologic appearance and clinical features. More recent, systematic studies have provided epidemiologic, clinicopathologic, and molecular support for these observations. Specifically, studies suggest that the most common type of endometrial carcinoma, endometrioid adenocarcinoma, develops from endometrial hyperplasia in the setting of excess estrogen exposure and usually pursues an indolent clinical course. In contrast, a minority of endometrial carcinomas, best represented by serous carcinoma, do not seem to be related to estrogenic risk factors or elevated serum hormone levels, and these tumors seem to develop from atrophic rather than hyperplastic epithelium. We have proposed that serous carcinomas develop from "endometrial intraepithelial carcinoma," a lesion representing malignant transformation of the endometrial surface epithelium. Whereas endometrioid carcinoma and endometrial hyperplasia are associated with microsatellite instability and ras and PTEN mutations, serous carcinoma and endometrial intraepithelial carcinoma are associated with p53 mutations and abnormal accumulation of p53 protein. Based on these data regarding the pathogenesis of endometrioid and serous carcinoma, we have proposed a dualistic model of endometrial carcinogenesis incorporating a "classic" estrogen-driven pathway and an "alternative" pathway seemingly unrelated to hormones. It is hoped that further studies may permit the extension and modification of this model and that these advances will lead to improved diagnosis, management, and prevention.

  19. Loss of HLTF function promotes intestinal carcinogenesis

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    Sandhu Sumit

    2012-03-01

    Full Text Available Abstract Background HLTF (Helicase-like Transcription Factor is a DNA helicase protein homologous to the SWI/SNF family involved in the maintenance of genomic stability and the regulation of gene expression. HLTF has also been found to be frequently inactivated by promoter hypermethylation in human colon cancers. Whether this epigenetic event is required for intestinal carcinogenesis is unknown. Results To address the role of loss of HLTF function in the development of intestinal cancer, we generated Hltf deficient mice. These mutant mice showed normal development, and did not develop intestinal tumors, indicating that loss of Hltf function by itself is insufficient to induce the formation of intestinal cancer. On the Apcmin/+ mutant background, Hltf- deficiency was found to significantly increase the formation of intestinal adenocarcinoma and colon cancers. Cytogenetic analysis of colon tumor cells from Hltf -/-/Apcmin/+ mice revealed a high incidence of gross chromosomal instabilities, including Robertsonian fusions, chromosomal fragments and aneuploidy. None of these genetic alterations were observed in the colon tumor cells derived from Apcmin/+ mice. Increased tumor growth and genomic instability was also demonstrated in HCT116 human colon cancer cells in which HLTF expression was significantly decreased. Conclusion Taken together, our results demonstrate that loss of HLTF function promotes the malignant transformation of intestinal or colonic adenomas to carcinomas by inducing genomic instability. Our findings highly suggest that epigenetic inactivation of HLTF, as found in most human colon cancers, could play an important role in the progression of colon tumors to malignant cancer.

  20. Multistage chemical carcinogenesis in mouse skin

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    Slaga, T.J.; Fischer, S.M.; Weeks, C.E.; Klein-Szanto, A.J.P.

    1979-01-01

    Skin tumors in mice can be induced by the sequential application of a subthreshold dose of a carcinogen (initiation phase) followed by repetitive treatment with a noncarcinogenic tumor promoter. The initiation phase requires only a single application of either a direct acting carcinogen or a procarcinogen which has to be metabolized before being active and is essentially an irreversible step which probably involves a somatic cell mutation. There is a good correlation between the skin tumor initiating activites of several polycyclic aromatic hydrocarbons (PAH) and their ability to bind covalently to epidermal DNA. Laboratory results suggest that bay region diol-epoxides are the ultimate carcinogenic form of PAH carcinogens. Potent inhibitors and stimulators of PAH tumor initiation appear to affect the level of the PAH diol-epoxide reacting with specific DNA bases. Reecent data suggests that the tumor promotion stage involves at least three important steps: (1) the induction of embryonic looking cells (dark cells) in adult epidermis; (2) an increased production of epidermal prostaglandins and polyamines; (3) sustained proliferation of dark cells. Retinoic acid specifically inhibits step two whereas the anti-inflammatory steriod fluocinolone acetonide is a potent inhibitor of steps one and three. The mechanism and the importance of a specific sequence for each step in chemical carcinogenesis in mouse skin are detailed.

  1. Hypoxia and Angiogenesis in Endometrioid Endometrial Carcinogenesis

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    Nicole Horrée

    2007-01-01

    Full Text Available Background: Hypoxia-inducible factor 1α (HIF-1α plays an essential role in the adaptive response of cells to hypoxia, triggering biologic events associated with aggressive tumor behavior. Methods: Expression of HIF-1α and proteins in the HIF-1α pathway (Glut-1, CAIX, VEGF in paraffin-embedded specimens of normal (n = 17, premalignant (n = 17 and endometrioid endometrial carcinoma (n = 39 was explored by immunohistochemistry, in relation to microvessel density (MVD. Results: HIF-1α overexpression was absent in inactive endometrium but present in hyperplasia (61% and carcinoma (87%, with increasing expression in a perinecrotic fashion pointing to underlying hypoxia. No membranous expression of Glut-1 and CAIX was noticed in inactive endometrium, in contrast with expression in hyperplasia (Glut-1 0%, CAIX 61%, only focal and diffuse and carcinoma (Glut-1 94.6%, CAIX 92%, both mostly perinecrotically. Diffuse HIF-1α was accompanied by activation of downstream targets. VEGF was significantly higher expressed in hyperplasias and carcinomas compared to inactive endometrium. MVD was higher in hyperplasias and carcinomas than in normal endometrium (p < 0.001. Conclusion: HIF-1α and its downstream genes are increasingly expressed from normal through premalignant to endometrioid adenocarcinoma of the endometrium, paralleled by activation of its downstream genes and increased angiogenesis. This underlines the potential importance of hypoxia and its key regulator HIF-1α in endometrial carcinogenesis.

  2. Carcinogenesis of pancreatic adenocarcinoma: precursor lesions.

    Science.gov (United States)

    Gnoni, Antonio; Licchetta, Antonella; Scarpa, Aldo; Azzariti, Amalia; Brunetti, Anna Elisabetta; Simone, Gianni; Nardulli, Patrizia; Santini, Daniele; Aieta, Michele; Delcuratolo, Sabina; Silvestris, Nicola

    2013-09-30

    Pancreatic adenocarcinoma displays a variety of molecular changes that evolve exponentially with time and lead cancer cells not only to survive, but also to invade the surrounding tissues and metastasise to distant sites. These changes include: genetic alterations in oncogenes and cancer suppressor genes; changes in the cell cycle and pathways leading to apoptosis; and also changes in epithelial to mesenchymal transition. The most common alterations involve the epidermal growth factor receptor (EGFR) gene, the HER2 gene, and the K-ras gene. In particular, the loss of function of tumor-suppressor genes has been documented in this tumor, especially in CDKN2a, p53, DPC4 and BRCA2 genes. However, other molecular events involved in pancreatic adenocarcinoma pathogenesis contribute to its development and maintenance, specifically epigenetic events. In fact, key tumor suppressors that are well established to play a role in pancreatic adenocarcinoma may be altered through hypermethylation, and oncogenes can be upregulated secondary to permissive histone modifications. Indeed, factors involved in tumor invasiveness can be aberrantly expressed through dysregulated microRNAs. This review summarizes current knowledge of pancreatic carcinogenesis from its initiation within a normal cell until the time that it has disseminated to distant organs. In this scenario, highlighting these molecular alterations could provide new clinical tools for early diagnosis and new effective therapies for this malignancy.

  3. Carcinogenesis of Pancreatic Adenocarcinoma: Precursor Lesions

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    Sabina Delcuratolo

    2013-09-01

    Full Text Available Pancreatic adenocarcinoma displays a variety of molecular changes that evolve exponentially with time and lead cancer cells not only to survive, but also to invade the surrounding tissues and metastasise to distant sites. These changes include: genetic alterations in oncogenes and cancer suppressor genes; changes in the cell cycle and pathways leading to apoptosis; and also changes in epithelial to mesenchymal transition. The most common alterations involve the epidermal growth factor receptor (EGFR gene, the HER2 gene, and the K-ras gene. In particular, the loss of function of tumor-suppressor genes has been documented in this tumor, especially in CDKN2a, p53, DPC4 and BRCA2 genes. However, other molecular events involved in pancreatic adenocarcinoma pathogenesis contribute to its development and maintenance, specifically epigenetic events. In fact, key tumor suppressors that are well established to play a role in pancreatic adenocarcinoma may be altered through hypermethylation, and oncogenes can be upregulated secondary to permissive histone modifications. Indeed, factors involved in tumor invasiveness can be aberrantly expressed through dysregulated microRNAs. This review summarizes current knowledge of pancreatic carcinogenesis from its initiation within a normal cell until the time that it has disseminated to distant organs. In this scenario, highlighting these molecular alterations could provide new clinical tools for early diagnosis and new effective therapies for this malignancy.

  4. Radioimmunotherapy improves survival of rats with microscopic liver metastases of colorectal origin.

    NARCIS (Netherlands)

    Jong, G.M. de; Hendriks, T.; Eek, A.; Oyen, W.J.G.; Heskamp, S.; Bleichrodt, R.P.; Boerman, O.C.

    2009-01-01

    BACKGROUND: Half of the patients with colorectal cancer develop liver metastases during the course of their disease. The aim of the present study was to assess the efficacy of radioimmunotherapy (RIT) with a radiolabeled monoclonal antibody (mAb) to treat experimental colorectal liver metastases.

  5. Identification of diagnostic markers in colorectal cancer via integrative epigenomics and genomics data.

    Science.gov (United States)

    Kok-Sin, Teow; Mokhtar, Norfilza Mohd; Ali Hassan, Nur Zarina; Sagap, Ismail; Mohamed Rose, Isa; Harun, Roslan; Jamal, Rahman

    2015-07-01

    Apart from genetic mutations, epigenetic alteration is a common phenomenon that contributes to neoplastic transformation in colorectal cancer. Transcriptional silencing of tumor-suppressor genes without changes in the DNA sequence is explained by the existence of promoter hypermethylation. To test this hypothesis, we integrated the epigenome and transcriptome data from a similar set of colorectal tissue samples. Methylation profiling was performed using the Illumina InfiniumHumanMethylation27 BeadChip on 55 paired cancer and adjacent normal epithelial cells. Fifteen of the 55 paired tissues were used for gene expression profiling using the Affymetrix GeneChip Human Gene 1.0 ST array. Validation was carried out on 150 colorectal tissues using the methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) technique. PCA and supervised hierarchical clustering in the two microarray datasets showed good separation between cancer and normal samples. Significant genes from the two analyses were obtained based on a ≥2-fold change and a false discovery rate (FDR) p-value of cancer tissues with high purity. The integrated analysis gives additional insight regarding the regulation of colorectal cancer-associated genes and their underlying mechanisms that contribute to colorectal carcinogenesis.

  6. Epigenetic-Mediated Downregulation of μ-Protocadherin in Colorectal Tumours

    Science.gov (United States)

    Mateusz, Bujko; Paulina, Kober; Małgorzata, Statkiewicz; Michal, Mikula; Marcin, Ligaj; Lech, Zwierzchowski; Jerzy, Ostrowski; Aleksander, Siedlecki Janusz

    2015-01-01

    Carcinogenesis involves altered cellular interaction and tissue morphology that partly arise from aberrant expression of cadherins. Mucin-like protocadherin is implicated in intercellular adhesion and its expression was found decreased in colorectal cancer (CRC). This study has compared MUPCDH (CDHR5) expression in three key types of colorectal tissue samples, for normal mucosa, adenoma, and carcinoma. A gradual decrease of mRNA levels and protein expression was observed in progressive stages of colorectal carcinogenesis which are consistent with reports of increasing MUPCDH 5′ promoter region DNA methylation. High MUPCDH methylation was also observed in HCT116 and SW480 CRC cell lines that revealed low gene expression levels compared to COLO205 and HT29 cell lines which lack DNA methylation at the MUPCDH locus. Furthermore, HCT116 and SW480 showed lower levels of RNA polymerase II and histone H3 lysine 4 trimethylation (H3K4me3) as well as higher levels of H3K27 trimethylation at the MUPCDH promoter. MUPCDH expression was however restored in HCT116 and SW480 cells in the presence of 5-Aza-2′-deoxycytidine (DNA methyltransferase inhibitor). Results indicate that μ-protocadherin downregulation occurs during early stages of tumourigenesis and progression into the adenoma-carcinoma sequence. Epigenetic mechanisms are involved in this silencing. PMID:25972897

  7. Periodontal disease, tooth loss and colorectal cancer risk: Results from the Nurses' Health Study.

    Science.gov (United States)

    Momen-Heravi, Fatemeh; Babic, Ana; Tworoger, Shelley S; Zhang, Libin; Wu, Kana; Smith-Warner, Stephanie A; Ogino, Shuji; Chan, Andrew T; Meyerhardt, Jeffrey; Giovannucci, Edward; Fuchs, Charles; Cho, Eunyoung; Michaud, Dominique S; Stampfer, Meir J; Yu, Yau-Hua; Kim, David; Zhang, Xuehong

    2017-02-01

    Periodontal diseases including tooth loss might increase systemic inflammation, lead to immune dysregulation and alter gut microbiota, thereby possibly influencing colorectal carcinogenesis. Few epidemiological studies have examined the association between periodontal diseases and colorectal cancer (CRC) risk. We collected information on the periodontal disease (defined as history of periodontal bone loss) and number of natural teeth in the Nurses' Health Study. A total of 77,443 women were followed since 1992. We used Cox proportional hazard models to calculate multivariable hazard ratios (HRs) and 95% confidence intervals (95% CIs) after adjustment for smoking and other known risk factors for CRC. We documented 1,165 incident CRC through 2010. Compared to women with 25-32 teeth, the multivariable HR (95% CI) for CRC for women with periodontal disease, HRs for CRC were 0.91 (95% CI 0.74-1.12) for periodontal disease, and 1.22 (95% CI 0.91-1.63) when limited to moderate to severe periodontal disease. The results were not modified by smoking status, body mass index or alcohol consumption. Women with fewer teeth, possibly moderate or severe periodontal disease, might be at a modest increased risk of developing CRC, suggesting a potential role of oral health in colorectal carcinogenesis. © 2016 UICC.

  8. Studies on promoting action in skin carcinogenesis

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    Saffiotti, U.; Shubik, P.

    1963-01-01

    A number of substances were tested for carcinogenic promoting activity in Swiss mice by applying them twice weekly to the clipped dorsal skin, beginning 1 wk after a single application of 9,10-dimethyl-1, 2-benzanthracene (DMBA; 1 to 1.5% in mineral oil). Tests with silver nitrate (10% aqueous), iodoacetic acid (0.9% in acetone, fumaric acid (1% in acetone), ethylphenylpropiolate (5% in acetone), trihydroxymethylanthraquinone. (Emodin; 0.5% in acetone), oleic alcohol, monostearin (5% in acetone) and sorbitan monolaurate were essentially negative; when a single application of croton oil (5% in mineral oil) was interspersed between the carcinogen and silver nitrate, 6/20 mice developed 14 benign tumors and 1 carcinoma. N-Dodecane showed moderate promoting activity (26 tumors, with 2 carcinomas, in 12/30 mice). Tests of several petroleum fractions showed high initial promoting activity (404 tumors, with 31 carcinomas, in 36/50 mice), but the activity disappeared on storage; while there was no carcinogenic activity in mice, in New Zealand albino rabbits the petroleum fractions alone produced considerable numbers of tumors. One application of DMBA, however, did increase tumor incidence and shorten the latent period. The hexane-eluted fraction of a methanolic extract of croton seeds (which had little vesicant activity), had all the promoting activity of the original croton oil; this could be demonstrated with uethan (20 mg/day ip for 5 days) as the initiator as well as with DMBA. In conclusion, the authors distinguish sharply between the promoting activity of compounds such as croton oil, which lead mostly to benign tumors (many of which regress spontaneously), and the additive effects of carcinogenic substances which may have a stimulatory effect on the second stage of carcinogenesis; for this additive carcinogenic effect, they suggest the term developing action. Other studies on croton oil are also reviewed.

  9. Allele-specific gene expression in carcinogenesis

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    O. M. Krivtsova

    2016-01-01

    Full Text Available Recent large-scale genomic studies established the occurrence of multiple DNA sequence variants in genomes of healthy individuals that differ from the reference sequence. Among these variants mostly represented by germline single nucleotide polymorphisms disease-related alleles are detected including alleles which are associated with monogenic disorders, and putative deleterious genetic variants. Apart from functional significance of a particular variant and of a gene harboring it, the penetrance of these allelic variants depends on their expression level and can be determined by preferential expression of a particular allele, or allele-specific expression. It is estimated that 20–30 % of genes present in the human genome display allelic bias in a tissue-specific manner. Allele-specific expression is defined by a range of genetic and epigenetic mechanisms including cis-regulatory polymorphisms, allele-specific binding of transcription factors, allele-specific DNA methylation and regulation through non-coding RNA.Although the data on the issue are scarce, allele-specific expression has been reported to be implicated in several hereditary disorders including benign and malignant tumors of the large intestine. Recent studies that estimate allele-specific expression incidence in tumors and identify wide range of genes displaying allelic imbalance indicate that allele-specific expression might play a significant role in carcinogenesis. Eventually, estimation of transcriptional rate of allelic variants which cause dysfunction of oncogenes and tumor suppressors may prove to be essential for rational choice of antitumor therapeutic strategy. In this review, we outline the main concepts and mechanisms of allele-specific expression and the data on allelic imbalance in tumors.

  10. Implications of tyrosine phosphoproteomics in cervical carcinogenesis

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    DeFord James

    2008-01-01

    Full Text Available Abstract Background Worldwide cervical cancer remains a leading cause of mortality from gynecologic malignancies. The link between cervical cancer and persistent infection with HPV has been established. At a molecular level little is known about the transition from the precancerous state to invasive cancer. To elucidate this process, cervical biopsies from human specimens were obtained from precancerous state to stage III disease. Methods Cervical biopsies were obtained from patients with a diagnosis of cervical cancer undergoing definitive surgery or staging operation. Biopsies were obtained from patients with precancerous lesions at the time of their excisional procedure. Control samples were obtained from patients undergoing hysterectomy for benign conditions such as fibroids. Samples were subjected to proteomic profiling using two dimensional gel electrophoresis with subsequent trypsin digestion followed by MALDI-TOF protein identification. Candidate proteins were then further studied using western blotting, immunoprecipitation and immunohistochemistry. Results Annexin A1 and DNA-PKcs were found to be differentially expressed. Phosphorylated annexin A1 was up regulated in diseased states in comparison to control and its level was strongly detected in the serum of cervical cancer patients compared to controls. DNA-PKcs was noted to be hyperphosphorylated and fragmented in cancer when compared to controls. By immunohistochemistry annexin A1 was noted in the vascular environment in cancer and certain precancerous samples. Conclusion This study suggests a probable role for protein tyrosine phosphorylation in cervical carcinogenesis. Annexin A1 and DNA-PK cs may have synergistic effects with HPV infection. Precancerous lesions that may progress to cervical cancer may be differentiated from lesions that will not base on similar immunohistochemical profile to invasive squamous cell carcinoma.

  11. The multidrug resistance 1 (MDR1) gene polymorphism G-rs3789243-A is not associated with disease susceptibility in Norwegian patients with colorectal adenoma and colorectal cancer; a case control study

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    Andersen, V.; Agerstjerne, L.; Jensen, D.

    2009-01-01

    Background: Smoking, dietary factors, and alcohol consumption are known life style factors contributing to gastrointestinal carcinogenesis. Genetic variations in carcinogen handling may affect cancer risk. The multidrug resistance 1(MDR1/ABCB1) gene encodes the transport protein P-glycoprotein (a...... in inflammation, and may thereby affect the risk of malignity. Hence, genetic variations that modify the function of P-glycoprotein may be associated with the risk of colorectal cancer (CRC). We have previously found an association between the MDR1 intron 3 G-rs3789243-A polymorphism and the risk of CRC...... was found between the MDR1 polymorphism (G-rs3789243-A) and colorectal adenomas or cancer. Carriers of the variant allele of MDR1 intron 3 had odds ratios (95% CI) of 0.97 (0.72-1.29) for developing adenomas, and 0.70 (0.41-1.21) for colorectal cancer, respectively, compared to homozygous wild type carriers...

  12. Folic acid, polymorphism of methyl-group metabolism genes, and DNA methylation in relation to GI carcinogenesis.

    Science.gov (United States)

    Fang, Jing Yuan; Xiao, Shu Dong

    2003-01-01

    DNA methylation is the main epigenetic modification after replication in humans. DNA (cytosine-5)-methyltransferase (DNMT) catalyzes the transfer of a methyl group from S-adenosyl-L-methionine (SAM) to C5 of cytosine within CpG dinucleotide sequences in the genomic DNA of higher eukaryotes. There is considerable evidence that aberrant DNA methylation plays an integral role in carcinogenesis. Folic acid or folate is crucial for normal DNA synthesis and can regulate DNA methylation, and through this, it affects cellular SAM levels. Folate deficiency results in DNA hypomethylation. Epidemiological studies have indicated that folic acid protects against gastrointestinal (GI) cancers. Methylene-tetrahydrofolate reductase (MTHFR) and methionine synthase (MS) are the enzymes involved in folate metabolism and are thought to influence DNA methylation. MTHFR is highly polymorphic, and the variant genotypes result in decreased MTHFR enzyme activity and lower plasma folate level. Two common MTHFR polymorphisms, 677CT (or 677TT) and A1298C, and an MS polymorphism, A-->G at 2756, have been identified. Most studies support an inverse association between folate status and the rate of colorectal adenomas and carcinomas. During human GI carcinogenesis, MTHFR is highly polymorphic, and the variant genotypes result in decreased MTHFR enzyme activity and lower plasma folate level, as well as aberrant methylation.

  13. Prevention of azoxymethane/dextran sodium sulfate-induced mouse colon carcinogenesis by processed Aloe vera gel.

    Science.gov (United States)

    Im, Sun-A; Kim, Ji-Wan; Kim, Hee-Suk; Park, Chan-Su; Shin, Eunju; Do, Seon-Gil; Park, Young In; Lee, Chong-Kil

    2016-11-01

    The preventive effect of a processed Aloe vera gel (PAG) on colon carcinogenesis was examined using an azoxymethane (AOM)-initiated and dextran sodium sulfate (DSS)-promoted mouse colon carcinogenesis model. Oral administration of PAG (200, or 400mg/kg/day) significantly reduced the multiplicity of colonic adenomas and adenocarcinomas compared with the AOM/DSS only-treated mice. In the mice treated with 400mg/kg of PAG, adenoma and adenocarcinoma development was reduced to 80% and 60%, respectively, compared to 100% in the PAG-untreated AOM/DSS-treated mice. Western blot analysis using colon extracts showed that PAG reduced the activation of nuclear factor kappa B (NF-κB), resulting in the inhibition of inducible nitric oxide synthase and cyclooxygenase-2 expression. PAG appeared to inhibit the NF-κB activation through the activation of peroxisome proliferator-activated receptor gamma. PAG also inhibited the expression and phosphorylation of signal transducer and activator of transcription 3, which is known to connect inflammation and cancer. In addition, PAG inhibited cell cycle progression-inducing cellular factors, such as extracellular signal-regulated kinases 1/2, cyclin-dependent kinase 4, and cyclin D1. On the other hand, PAG increased the expression of Caudal-related homeobox transcription factor 2, which is known to be a tumor suppressor in colorectal cancer. These findings show that PAG suppresses colitis-related colon carcinogenesis by inhibiting both chronic inflammation and cell cycle progression in the colon. Copyright © 2016 Elsevier B.V. All rights reserved.

  14. [Nationwide colorectal cancer screening].

    NARCIS (Netherlands)

    Rossum, L.G.M. van; Laheij, R.J.F.; Jansen, J.B.M.J.

    2010-01-01

    Usually, colorectal cancer presents with complaints in a late stage, but can be detected in an earlier stage, with better prognosis, by colonoscopy. Using colonoscopy, also precancerous tumours, adenomas, can be detected and excised, but only in a national screening programme. However primary

  15. Mechanisms linking excess adiposity and carcinogenesis promotion

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    Ana I. Pérez-Hernández

    2014-05-01

    Full Text Available Obesity constitutes one of the most important metabolic diseases being associated to insulin resistance development and increased cardiovascular risk. Association between obesity and cancer has also been well-established for several tumor types, such as breast cancer in postmenopausal women, colorectal and prostate cancer. Cancer is the first death cause in developed countries and the second one in developing countries, with high incidence rates around the world. Furthermore, it has been estimated that 15-20% of all cancer deaths may be attributable to obesity. Tumor growth is regulated by interactions between tumor cells and their tissue microenvironment. In this sense, obesity may lead to cancer development through dysfunctional adipose tissue and altered signaling pathways. In this review, three main pathways relating obesity and cancer development are examined: i inflammatory changes leading to macrophage polarization and altered adipokine profile; ii insulin resistance development; and iii adipose tissue hypoxia. Since obesity and cancer present a high prevalence, the association between these conditions is of great public health significance and studies showing mechanisms by which obesity lead to cancer development and progression are needed to improve prevention and management of these diseases.

  16. Mechanisms Linking Excess Adiposity and Carcinogenesis Promotion

    Science.gov (United States)

    Pérez-Hernández, Ana I.; Catalán, Victoria; Gómez-Ambrosi, Javier; Rodríguez, Amaia; Frühbeck, Gema

    2014-01-01

    Obesity constitutes one of the most important metabolic diseases being associated to insulin resistance development and increased cardiovascular risk. Association between obesity and cancer has also been well established for several tumor types, such as breast cancer in post-menopausal women, colorectal, and prostate cancer. Cancer is the first death cause in developed countries and the second one in developing countries, with high incidence rates around the world. Furthermore, it has been estimated that 15–20% of all cancer deaths may be attributable to obesity. Tumor growth is regulated by interactions between tumor cells and their tissue microenvironment. In this sense, obesity may lead to cancer development through dysfunctional adipose tissue and altered signaling pathways. In this review, three main pathways relating obesity and cancer development are examined: (i) inflammatory changes leading to macrophage polarization and altered adipokine profile; (ii) insulin resistance development; and (iii) adipose tissue hypoxia. Since obesity and cancer present a high prevalence, the association between these conditions is of great public health significance and studies showing mechanisms by which obesity lead to cancer development and progression are needed to improve prevention and management of these diseases. PMID:24829560

  17. [Nutrition and colorectal cancer].

    Science.gov (United States)

    Ströhle, Alexander; Maike, Wolters; Hahn, Andreas

    2007-01-01

    Diet plays an important role in the pathogenesis of colorectal cancer. Current prospective cohort studies and metaanalysis enable a reevaluation of how food or nutrients such as fiber and fat influence cancer risk. Based on the evidence criteria of the WHO/FAD, risk reduction by a high intake of fruit is assessed as possible, while a lowered risk by a high vegetable intake is probable. Especially raw vegetables and fruits seem to exert anticancer properties. The evidence of a risk reducing effect of whole grain relating to colorectal cancer is assessed as probable whereas the evidence of an increased risk by high consumption of refined white flour products and sweets is (still) insufficient despite some evidences. There is a probable risk reducing effect of milk and dairy products. e available data on eggs and red meat indicate a possible risk increasing influence. Stronger clues for a risk increasing effect have been shown for meat products leading to an evidence assessed as probable. Owing to varied interpretations of the data on fiber, the evidence of a risk reducing effect relating to colorectal cancer is assessed as possible or insufficient. The available data on alcohol consumption indicate a possible risk increasing effect. In contrast to former evaluations, diets rich in fat seem to increase colorectal cancer risk only indirectly as part of a hypercaloric diet by advancing the obesity risk. Thus, the evidence of obesity, especially visceral obesity, as a risk of colorectal cancer is judged as convincing today. Prospective cohort studies suggest that people who get higher than average amounts of folic acid from multivitamin supplements have lower risks of colorectal cancer. The evidence for a risk reducing effect of calcium, selenium, vitamin D and vitamin E on colorectal cancer is insufficient. As primary prevention, a diet rich in vegetables, fruits, whole grain products, and legumes added by low-fat dairy products, fish, and poultry can be recommended. In

  18. The leptin gene family and colorectal cancer: interaction with smoking behavior and family history of cancer.

    Science.gov (United States)

    Liu, Li; Zhong, Rong; Wei, Sheng; Xiang, Hao; Chen, Jigui; Xie, Duoshuang; Yin, Jieyun; Zou, Li; Sun, Jingwen; Chen, Wei; Miao, Xiaoping; Nie, Shaofa

    2013-01-01

    Pathologic condition associated with metabolic syndrome traits seems to increase the risk of colorectal cancer. One mechanism underlying this relationship may involve the growth-promoting effects of the circulation hormones associated with obesity and insulin resistance, such as leptin. A two-stage case-control study was used to explore the role of polymorphisms of Leptin (LEP) and Leptin receptor (LEPR), either alone or in combination with environmental factors in colorectal carcinogenesis. In stage 1, 20 single nucleotide polymorphisms (SNPs) that tag common SNPs in these two genes were genotyped among 470 cases and 458 controls. In stage 2, another population with 314 cases and 355 controls were genotyped for the two most promising SNPs from stage 1. LEPR rs12037879 only presented modestly increased colorectal cancer risk, with odds ratios of 1.41 (95% confidence interval [CI] 1.13-1.76) and 1.74 (95%CI 1.08-2.81) for GA and AA genotype when compared with GG genotype in combined population. Smokers carrying LEPR rs12037879 A allele presented 1.67-fold (95%CI 1.39-fold to 2.01-fold) increased colorectal cancer risk when compared with non-smokers carrying GG genotype in combined analysis. Individuals with family history of cancer harboring LEPR rs12037879 A allele showed 1.52-fold (95%CI: 1.24-fold to 1.86-fold) increased colorectal cancer risk, compared with individuals without family history of cancer harboring GG genotype. Multifactor gene-environment interaction analysis revealed significant interactions among LEPR rs12037879, LEPR rs6690625, smoking status and family history of cancer, exhibiting a gradient of increased colorectal cancer risk along with the increasing number of risk factors (P = 9.82 × 10(-10)). Our research supports that polymorphisms in LEPR may be associated with marginal increase in the risk for colorectal cancer. Moreover, this association could be strengthened by cigarette smoking and family history of cancer.

  19. Plasma matrix metalloproteinase 9 as an early surrogate biomarker of advanced colorectal neoplasia.

    Science.gov (United States)

    Gimeno-García, Antonio Z; Triñanes, Javier; Quintero, Enrique; Salido, Eduardo; Nicolás-Pérez, David; Adrián-de-Ganzo, Zaida; Alarcón-Fernández, Onofre; Abrante, Beatriz; Romero, Rafael; Carrillo, Marta; Ramos, Laura; Alonso, Inmaculada; Ortega, Juan; Jiménez, Alejandro

    2016-01-01

    Matrix metalloproteinases (MMPs) are overexpressed at different stages of colorectal carcinogenesis and could serve as early surrogate biomarkers of colorectal neoplasia. To assess the utility of plasma MMP2 and MMP9 levels in the detection of advanced colorectal neoplasia and their correlation with tissue levels. We analysed blood and tissue samples from patients with non-advanced adenomas (n=25), advanced adenomas (n=25), colorectal cancer (n=25) and healthy controls (n=75). Plasma and tissue gelatinase levels were determined by Luminex XMAP technology and gelatin zymography. Receiver operating characteristic (ROC) curve analysis was used to calculate the optimum cut-off for the detection of advanced colorectal neoplasia. Plasma MMP2 levels were similar between groups whatever the type of lesion. Plasma MMP9 levels were significantly higher in patients with neoplastic lesions than in healthy controls (median 292.3ng/ml vs. 139.08ng/ml, P<0.001). MMP9 levels were also higher in colorectal cancer than in non-advanced adenomas (median 314.6ng/ml vs. 274.3ng/ml, P=0.03). There was a significant correlation between plasma and tissue levels of MMP9 (r=0.5, P<0.001). The plasma MMP9 cut-off range with the highest diagnostic accuracy was between 173ng/ml and 204ng/ml (AUC=0.80 [95% CI: 0.72-0.86], P<0.001; sensitivity, 80-86% and specificity, 57-67%). Plasma MMP9 could be a surrogate biomarker for the early detection of advanced colorectal neoplasia, although its diagnostic performance could be increased by combination with other biomarkers. Copyright © 2015 Elsevier España, S.L.U. y AEEH y AEG. All rights reserved.

  20. Molecular genetic changes in benign colorectal tumors synchronous with microsatellite unstable carcinomas do not support a field defect

    Science.gov (United States)

    Zauber, Peter; Marotta, Stephen; Sabbath-Solitare, Marlene

    2017-01-01

    Background: A colorectal cancer may develop through a particular molecular genetic pathway, raising the question of whether the particular molecular changes are random, or are unique to the particular segment of colon. We wanted to determine whether molecular changes found within a colorectal cancer might also be detected in separate adenomas and polyps removed from the same area of colon at surgery. Microsatellite instability was chosen as a marker for a pathway of colon carcinogenesis. Methods: We studied a total of 46 primary colorectal cancers with microsatellite instability and 77 synchronous adenomas and polyps. All tumors were evaluated for microsatellite instability, BRAF and KRAS mutations, and methylation using standard polymerase chain reaction based methods. Results: Forty-nine benign tumors did not follow a pathway similar to that of their 31 synchronous primary cancers. For two distinct subsets of the microsatellite unstable colorectal cancers, those with acquired methylation and BRAF mutation, and those without methylation suggestive of an underlying germ line mutation, the molecular changes in the majority of their synchronous benign tumors were different from the colorectal cancer. Conclusions: These differences suggest a stochastic process within the colon regarding the particular molecular carcinogenic pathways followed by the synchronous tumors, rather than a ‘field defect’ within the colon segments. Variability in molecular findings was present for colorectal cancers arising from acquired methylation, as well as those cancers suggestive of a germ line origin. PMID:28694923

  1. Systematic enrichment analysis of gene expression profiling studies identifies consensus pathways implicated in colorectal cancer development

    Directory of Open Access Journals (Sweden)

    Jesús Lascorz

    2011-01-01

    Full Text Available Background: A large number of gene expression profiling (GEP studies on colorectal carcinogenesis have been performed but no reliable gene signature has been identified so far due to the lack of reproducibility in the reported genes. There is growing evidence that functionally related genes, rather than individual genes, contribute to the etiology of complex traits. We used, as a novel approach, pathway enrichment tools to define functionally related genes that are consistently up- or down-regulated in colorectal carcinogenesis. Materials and Methods: We started the analysis with 242 unique annotated genes that had been reported by any of three recent meta-analyses covering GEP studies on genes differentially expressed in carcinoma vs normal mucosa. Most of these genes (218, 91.9% had been reported in at least three GEP studies. These 242 genes were submitted to bioinformatic analysis using a total of nine tools to detect enrichment of Gene Ontology (GO categories or Kyoto Encyclopedia of Genes and Genomes (KEGG pathways. As a final consistency criterion the pathway categories had to be enriched by several tools to be taken into consideration. Results: Our pathway-based enrichment analysis identified the categories of ribosomal protein constituents, extracellular matrix receptor interaction, carbonic anhydrase isozymes, and a general category related to inflammation and cellular response as significantly and consistently overrepresented entities. Conclusions: We triaged the genes covered by the published GEP literature on colorectal carcinogenesis and subjected them to multiple enrichment tools in order to identify the consistently enriched gene categories. These turned out to have known functional relationships to cancer development and thus deserve further investigation.

  2. Role of bile acids in carcinogenesis of pancreatic cancer: An old topic with new perspective.

    Science.gov (United States)

    Feng, Hui-Yi; Chen, Yang-Chao

    2016-09-07

    The role of bile acids in colorectal cancer has been well documented, but their role in pancreatic cancer remains unclear. In this review, we examined the risk factors of pancreatic cancer. We found that bile acids are associated with most of these factors. Alcohol intake, smoking, and a high-fat diet all lead to high secretion of bile acids, and bile acid metabolic dysfunction is a causal factor of gallstones. An increase in secretion of bile acids, in addition to a long common channel, may result in bile acid reflux into the pancreatic duct and to the epithelial cells or acinar cells, from which pancreatic adenocarcinoma is derived. The final pathophysiological process is pancreatitis, which promotes dedifferentiation of acinar cells into progenitor duct-like cells. Interestingly, bile acids act as regulatory molecules in metabolism, affecting adipose tissue distribution, insulin sensitivity and triglyceride metabolism. As a result, bile acids are associated with three risk factors of pancreatic cancer: obesity, diabetes and hypertriglyceridemia. In the second part of this review, we summarize several studies showing that bile acids act as cancer promoters in gastrointestinal cancer. However, more question are raised than have been solved, and further oncological and physiological experiments are needed to confirm the role of bile acids in pancreatic cancer carcinogenesis.

  3. Intestinal helminth infection drives carcinogenesis in colitis-associated colon cancer.

    Directory of Open Access Journals (Sweden)

    Eva Pastille

    2017-09-01

    Full Text Available Inflammatory bowel diseases (IBD are chronic inflammatory disorders of the gastrointestinal tract, strongly associated with an increased risk of colorectal cancer development. Parasitic infections caused by helminths have been shown to modulate the host's immune response by releasing immunomodulatory molecules and inducing regulatory T cells (Tregs. This immunosuppressive state provoked in the host has been considered as a novel and promising approach to treat IBD patients and alleviate acute intestinal inflammation. On the contrary, specific parasite infections are well known to be directly linked to carcinogenesis. Whether a helminth infection interferes with the development of colitis-associated colon cancer (CAC is not yet known. In the present study, we demonstrate that the treatment of mice with the intestinal helminth Heligmosomoides polygyrus at the onset of tumor progression in a mouse model of CAC does not alter tumor growth and distribution. In contrast, H. polygyrus infection in the early inflammatory phase of CAC strengthens the inflammatory response and significantly boosts tumor development. Here, H. polygyrus infection was accompanied by long-lasting alterations in the colonic immune cell compartment, with reduced frequencies of colonic CD8+ effector T cells. Moreover, H. polygyrus infection in the course of dextran sulfate sodium (DSS mediated colitis significantly exacerbates intestinal inflammation by amplifying the release of colonic IL-6 and CXCL1. Thus, our findings indicate that the therapeutic application of helminths during CAC might have tumor-promoting effects and therefore should be well-considered.

  4. Green tea catechin intervention of reactive oxygen species-mediated ERK pathway activation and chronically induced breast cell carcinogenesis

    Science.gov (United States)

    Rathore, Kusum; Choudhary, Shambhunath; Odoi, Agricola; Wang, Hwa-Chain R.

    2012-01-01

    Long-term exposure to low doses of environmental carcinogens contributes to sporadic human breast cancers. Epidemiologic and experimental studies indicate that green tea catechins (GTCs) may intervene with breast cancer development. We have been developing a chronically induced breast cell carcinogenesis model wherein we repeatedly expose non-cancerous, human breast epithelial MCF10A cells to bioachievable picomolar concentrations of environmental carcinogens, such as 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and benzo[a]pyrene (B[a]P), to progressively induce cellular acquisition of cancer-associated properties, as measurable end points. The model is then used as a target to identify non-cytotoxic preventive agents effective in suppression of cellular carcinogenesis. Here, we demonstrate, for the first time, a two-step strategy that initially used end points that were transiently induced by short-term exposure to NNK and B[a]P as targets to detect GTCs capable of blocking the acquisition of cancer-associated properties and subsequently used end points constantly induced by long-term exposure to carcinogens as targets to verify GTCs capable of suppressing carcinogenesis. We detected that short-term exposure to NNK and B[a]P resulted in elevation of reactive oxygen species (ROS), leading to Raf-independent extracellular signal-regulated kinase (ERK) pathway activation and subsequent induction of cell proliferation and DNA damage. These GTCs, at non-cytotoxic levels, were able to suppress chronically induced cellular carcinogenesis by blocking carcinogen-induced ROS elevation, ERK activation, cell proliferation and DNA damage in each exposure cycle. Our model may help accelerate the identification of preventive agents to intervene in carcinogenesis induced by long-term exposure to environmental carcinogens, thereby safely and effectively reducing the health risk of sporadic breast cancer. PMID:22045026

  5. Oral Carcinogenesis and Oral Cancer Chemoprevention: A Review

    Directory of Open Access Journals (Sweden)

    Takuji Tanaka

    2011-01-01

    Full Text Available Oral cancer is one of the major global threats to public health. The development of oral cancer is a tobacco-related multistep and multifocal process involving field cancerization and carcinogenesis. The rationale for molecular-targeted prevention of oral cancer is promising. Biomarkers of genomic instability, including aneuploidy and allelic imbalance, are possible to measure the cancer risk of oral premalignancies. Understanding of the biology of oral carcinogenesis will yield important advances for detecting high-risk patients, monitoring preventive interventions, and assessing cancer risk and pharmacogenomics. In addition, novel chemopreventive agents based on molecular mechanisms and targets against oral cancers will be derived from studies using appropriate animal carcinogenesis models. New approaches, such as molecular-targeted agents and agent combinations in high-risk oral individuals, are undoubtedly needed to reduce the devastating worldwide consequences of oral malignancy.

  6. Risks of Colorectal Cancer Screening

    Science.gov (United States)

    ... Types Bladder Cancer Breast Cancer Colorectal Cancer Kidney (Renal Cell) Cancer Leukemia Liver Cancer Lung Cancer Lymphoma Pancreatic Cancer Prostate Cancer Skin Cancer Thyroid Cancer Uterine Cancer All ...

  7. The Hamster Buccal Pouch Model of Oral Carcinogenesis.

    Science.gov (United States)

    Nagini, Siddavaram; Kowshik, Jaganathan

    2016-01-01

    The hamster buccal pouch (HBP) carcinogenesis model is one of the most well-characterized animal tumor models used as a prelude to investigate multistage oral carcinogenesis and to assess the efficacy of chemointervention. Hamster buccal pouch carcinomas induced by 7,12-dimethylbenz[a]anthracene (DMBA) show extensive similarities to human oral squamous cell carcinomas. The HBP model offers a number of advantages including a simple and predictable tumor induction procedure, easy accessibility for examination and follow-up of lesions, and reproducibility. This model can be used to test both chemopreventive and chemotherapeutic agents.

  8. Synergistic role of curcumin with current therapeutics in colorectal cancer: minireview.

    Science.gov (United States)

    Patel, Bhaumik B; Majumdar, Adhip P N

    2009-01-01

    Despite the use of surgical resection and aggressive chemotherapy, nearly 50% of patients with colorectal carcinoma develop recurrent disease, highlighting the need for improved therapies. Curcumin (diferuloylmethane), the major active ingredient of turmeric (curcuma longa) with no discernable toxicity, has been shown to inhibit the growth of transformed cells and colon carcinogenesis at the initiation, promotion, and progression stages in carcinogen-induced rodent models. In a Phase I clinical trial, curcumin has been found to be extremely well tolerated and effective. In this review, we summarized the current status of our knowledge about the effectiveness of curcumin when given in combination with current chemotherapeutics such as 5-fluorouracil, oxaliplatin, and gemcitabine in treatment of gastrointestinal cancers with particular reference to colorectal cancer. Existing data suggest that curcumin in combination with chemotherapy is a superior strategy for treatment of gastrointestinal cancer.

  9. Expression of NDRG2 is down-regulated in high-risk adenomas and colorectal carcinoma

    DEFF Research Database (Denmark)

    Lorentzen, Anders; Vogel, Lotte K.; Lewinsky, Rikke H

    2007-01-01

    to examine NDRG2 mRNA expression in colon cancer. By examining affected and normal tissue from individuals with colorectal adenomas and carcinomas, as well as in healthy individuals, we aim to determine whether and at which stages NDRG2 down-regulation occurs during colonic carcinogenesis. METHODS: Using......BACKGROUND: It has recently been shown that NDRG2 mRNA is down-regulated or undetectable in several human cancers and cancer cell-lines. Although the function of NDRG2 is unknown, high NDRG2 expression correlates with improved prognosis in high-grade gliomas. The aim of this study has been......-regulation is a cause or consequence of the progression of colorectal adenomas to carcinoma....

  10. Sex differences in the association of obesity and colorectal cancer risk.

    Science.gov (United States)

    Kim, Hanseul; Giovannucci, Edward L

    2017-01-01

    Epidemiological research has convincingly shown that obesity increases colorectal cancer (CRC) risk, with generally stronger associations observed in men than in women. Evidence from the past several years has demonstrated a divergent pattern between men and women regarding the weight changes throughout life or timing of obesity for CRC risk. For men, weight gain later in life appears to be an important risk factor for CRC that mostly accounts for their generally strong association between adult body mass index and CRC risk. For women, however, early life obesity seems to be more important than adult weight gain in determining CRC risk. A knowledge of these sex patterns may have implications on better understanding colorectal carcinogenesis and may further improve prevention efforts for CRC.

  11. High frequency of RPL22 mutations in microsatellite-unstable colorectal and endometrial tumors.

    Science.gov (United States)

    Ferreira, Ana M; Tuominen, Iina; van Dijk-Bos, Krista; Sanjabi, Bahram; van der Sluis, Tineke; van der Zee, Ate G; Hollema, Harry; Zazula, Monika; Sijmons, Rolf H; Aaltonen, Lauri A; Westers, Helga; Hofstra, Robert M W

    2014-12-01

    Ribosomal Protein L22 (RPL22) encodes a protein that is a component of the 60S subunit of the ribosome. Variants in this gene have recently been linked to cancer development. Mutations in an A8 repeat in exon 2 were found in a recent study in 52% of microsatellite-unstable endometrial tumors. These tumors are particularly prone to mutations in repeats due to mismatch repair deficiency. We screened this coding repeat in our collection of microsatellite-unstable endometrial tumors (EC) and colorectal tumors (CRC). We found 50% mutation frequency for EC and 77% mutation frequency for CRC. These results confirm the previous study on the involvement of RPL22 in EC and, more importantly, reports for the first time such high mutation frequency in this gene in colorectal cancer. Furthermore, considering the high mutation frequency found, our data point toward an important role for RPL22 in microsatellite instability carcinogenesis. © 2014 WILEY PERIODICALS, INC.

  12. Interactions between meat intake and genetic variation in relation to colorectal cancer

    DEFF Research Database (Denmark)

    Andersen, Vibeke; Vogel, Ulla

    2015-01-01

    Meat intake is associated with the risk of colorectal cancer. The objective of this systematic review was to evaluate interactions between meat intake and genetic variation in order to identify biological pathways involved in meat carcinogenesis. We performed a literature search of Pub......Med and Embase using "interaction", "meat", "polymorphisms", and "colorectal cancer", and data on meat-gene interactions were extracted. The studies were divided according to whether information on meat intake was collected prospectively or retrospectively. In prospective studies, interactions between meat...... a polymorphism in XPC and meat was found in one prospective and one case-control study; however, the directions of the risk estimates were opposite. Thus, none of the findings were replicated. The results from this systematic review suggest that genetic variation in the inflammatory response and DNA repair...

  13. [Colorectal cancer screening].

    Science.gov (United States)

    Castells, Antoni

    2013-10-01

    Colorectal cancer is the paradigm of tumoral growth that is susceptible to preventive measures, especially screening. Various screening strategies with demonstrated efficacy and efficiency are currently available, notable examples being the fecal occult blood test and endoscopic tests. In addition, new modalities have appeared in the last few years that could become viable alternatives in the near future. The present article reviews the most important presentations on colorectal screening at the annual congress of the American Gastroenterological Association held in Orlando in May 2013, with special emphasis on the medium- and long-term results of strategies using the fecal occult blood test and flexible sigmoidoscopy, as well as initial experiences with the use of new biomarkers. Copyright © 2013 Elsevier España, S.L. All rights reserved.

  14. [Colorectal cancer screening].

    Science.gov (United States)

    Castells, Antoni

    2015-09-01

    Colorectal cancer is one of malignancies showing the greatest benefit from preventive measures, especially screening or secondary prevention. Several screening strategies are available with demonstrated efficacy and efficiency. The most widely used are the faecal occult blood test in countries with population-based screening programmes, and colonoscopy in those conducting opportunistic screening. The present article reviews the most important presentations on colorectal cancer screening at the annual congress of the American Gastroenterological Association held in Washington in 2015, with special emphasis on the medium-term results of faecal occult blood testing strategies and determining factors and on strategies to reduce the development of interval cancer after colonoscopy. Copyright © 2015 Elsevier España, S.L.U. All rights reserved.

  15. Screening for colorectal cancer

    DEFF Research Database (Denmark)

    Nielsen, Hans J; Jakobsen, Karen V; Christensen, Ib J

    2011-01-01

    Emerging results indicate that screening improves survival of patients with colorectal cancer. Therefore, screening programs are already implemented or are being considered for implementation in Asia, Europe and North America. At present, a great variety of screening methods are available including...... colono- and sigmoidoscopy, CT- and MR-colonography, capsule endoscopy, DNA and occult blood in feces, and so on. The pros and cons of the various tests, including economic issues, are debated. Although a plethora of evaluated and validated tests even with high specificities and reasonable sensitivities...... into improvements of screening for colorectal cancer includes blood-based biological markers, such as proteins, DNA and RNA in combination with various demographically and clinically parameters into a "risk assessment evaluation" (RAE) test. It is assumed that such a test may lead to higher acceptance among...

  16. The gut microbiota in conventional and serrated precursors of colorectal cancer.

    Science.gov (United States)

    Peters, Brandilyn A; Dominianni, Christine; Shapiro, Jean A; Church, Timothy R; Wu, Jing; Miller, George; Yuen, Elizabeth; Freiman, Hal; Lustbader, Ian; Salik, James; Friedlander, Charles; Hayes, Richard B; Ahn, Jiyoung

    2016-12-30

    of colorectal carcinogenesis through the development of CAs. Findings may have implications for developing colorectal cancer prevention therapies targeting early microbial drivers of colorectal carcinogenesis.

  17. Immortalized Cancer-associated Fibroblasts Promote Prostate Cancer Carcinogenesis, Proliferation and Invasion.

    Science.gov (United States)

    Yu, Shengqiang; Jiang, Yingjuan; Wan, Fengchun; Wu, Jitao; Gao, Zhenli; Liu, Dongfu

    2017-08-01

    Cancer-associated fibroblasts (CAFs) are dominant components of the prostate cancer (PCa) stroma. However, the contrasting effects of CAFs and adjacent normal prostate fibroblasts (NPFs) are still poorly defined. The senescence of non-immortalized CAFs after subculture may limit the cell number and influence experimental results of in vitro studies. In this study, we immortalized CAFs to study their role in PCa carcinogenesis, proliferation, and invasion. We cultured and immortalized CAFs and NPFs, then compared their effect on epithelial malignant transformation by using in vitro co-culture, soft agar assay, and a mouse renal capsule xenograft model. We also compared their roles in PCa progression by using in vitro co-culture, cell viability assays, invasion assays, and a mouse xenograft model. For the mechanistic study, we screened a series of growth factors by using real-time polymerase chain reaction. The CAFs and NPFs were successfully cultured, immortalized, and characterized. The CAFs were able to transform prostate epithelial cells into malignant cells, but NPFs were not. The CAFs were more active in promoting proliferation of and invasion by PCa cells, and in secreting higher levels of a series of growth factors. The immortalized CAFs were more supportive of PCa carcinogenesis and progression. Targeting CAFs might be a potential option for PCa therapy. Immortalized CAFs and NPFs will also be valuable resources for future experimental exploration. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  18. The Association of Low-Penetrance Variants in DNA Repair Genes with Colorectal Cancer: A Systematic Review and Meta-Analysis

    OpenAIRE

    Aggarwal, Nikhil; Donald, Neil D; Malik, Salim; Selvendran, Subothini S; McPhail, Mark JW.; Monahan, Kevin J

    2017-01-01

    Objectives: Approximately 35% of colorectal cancer (CRC) risk is attributable to heritable factors known hereditary syndromes, accounting for 6%. The remainder may be due to lower penetrance polymorphisms particularly of DNA repair genes. DNA repair pathways, including base excision repair (BER), nucleotide excision repair (NER), mismatch repair (MMR), direct reversal repair (DRR), and double-strand break repair are complex, evolutionarily conserved, and critical in carcinogenesis. Germline m...

  19. Improving colorectal cancer referrals

    OpenAIRE

    Gregory, Claire

    2018-01-01

    The colorectal services at The Royal Bournemouth Hospital needed to adapt to meet the extra demand on fast-track patient referrals to the outpatient department, as a consequence of the changes in the National Institute for Health and Care Excellence (NICE) guidance on cancer referrals in June 2015. Learning from other units, a telephone assessment clinic (TAC) triaging patients straight to colonoscopy was trialled. A Plan–Do–Study–Act (PDSA) methodology was used. A baseline study showed that ...

  20. Colorectal cancer screening.

    Science.gov (United States)

    Bessa Caserras, Xavier

    2016-09-01

    In the latest meeting of the American Gastroenterological Association, several clinical studies were presented that aimed to evaluate the various colorectal cancer screening strategies, although most assessed the various aspects of faecal immunochemical testing (FIT) and colonoscopy. Data were presented from consecutive FIT-based screening rounds, confirming the importance of adherence to consecutive screening rounds, achieving a similar or superior diagnostic yield to endoscopic studies. There was confirmation of the importance of not delaying endoscopic study after a positive result. Participants with a negative FIT (score of 0) had a low risk for colorectal cancer. Several studies seemed to confirm the importance of high-quality colonoscopy in colorectal cancer screening programmes. The implementation of high-quality colonoscopies has reduced mortality from proximal lesions and reduced interval cancers in various studies. Finally, participants with a normal colonoscopy result or with a small adenoma are at low risk for developing advanced neoplasms during follow-up. Copyright © 2016 Elsevier España, S.L.U. All rights reserved.

  1. The role of tissue factor in colorectal cancer

    DEFF Research Database (Denmark)

    Lykke, J; Nielsen, Hans Jørgen

    2003-01-01

    The possible role of tissue factor (TF) in colorectal cancer (CRC) is reviewed. A correlation between TF expression and advanced stages of malignancy, and a correlation between TF expression and overall survival have been suggested in CRC. This is supported by experimental studies indicating...

  2. Metabolic reprogramming and dysregulated metabolism: cause, consequence and/or enabler of environmental carcinogenesis?

    Science.gov (United States)

    Robey, R.Brooks; Weisz, Judith; Kuemmerle, Nancy; Salzberg, Anna C.; Berg, Arthur; Brown, Dustin G.; Kubik, Laura; Palorini, Roberta; Al-Mulla, Fahd; Al-Temaimi, Rabeah; Colacci, Annamaria; Mondello, Chiara; Raju, Jayadev; Woodrick, Jordan; Scovassi, A.Ivana; Singh, Neetu; Vaccari, Monica; Roy, Rabindra; Forte, Stefano; Memeo, Lorenzo; Salem, Hosni K.; Amedei, Amedeo; Hamid, Roslida A.; Williams, Graeme P.; Lowe, Leroy; Meyer, Joel; Martin, Francis L.; Bisson, William H.; Chiaradonna, Ferdinando; Ryan, Elizabeth P.

    2015-01-01

    Environmental contributions to cancer development are widely accepted, but only a fraction of all pertinent exposures have probably been identified. Traditional toxicological approaches to the problem have largely focused on the effects of individual agents at singular endpoints. As such, they have incompletely addressed both the pro-carcinogenic contributions of environmentally relevant low-dose chemical mixtures and the fact that exposures can influence multiple cancer-associated endpoints over varying timescales. Of these endpoints, dysregulated metabolism is one of the most common and recognizable features of cancer, but its specific roles in exposure-associated cancer development remain poorly understood. Most studies have focused on discrete aspects of cancer metabolism and have incompletely considered both its dynamic integrated nature and the complex controlling influences of substrate availability, external trophic signals and environmental conditions. Emerging high throughput approaches to environmental risk assessment also do not directly address the metabolic causes or consequences of changes in gene expression. As such, there is a compelling need to establish common or complementary frameworks for further exploration that experimentally and conceptually consider the gestalt of cancer metabolism and its causal relationships to both carcinogenesis and the development of other cancer hallmarks. A literature review to identify environmentally relevant exposures unambiguously linked to both cancer development and dysregulated metabolism suggests major gaps in our understanding of exposure-associated carcinogenesis and metabolic reprogramming. Although limited evidence exists to support primary causal roles for metabolism in carcinogenesis, the universality of altered cancer metabolism underscores its fundamental biological importance, and multiple pleiomorphic, even dichotomous, roles for metabolism in promoting, antagonizing or otherwise enabling the

  3. Anti-Warburg effect of rosmarinic acid via miR-155 in colorectal carcinoma cells.

    Science.gov (United States)

    Xu, Yichun; Han, Shuai; Lei, Kesheng; Chang, Xinnan; Wang, Ke; Li, Zhou; Liu, Jianwen

    2016-11-01

    The Warburg effect, glycolytic production of ATP under aerobic conditions, is found to be a universal feature of most cancer cells. Our study was aimed to determine whether rosmarinic acid (RA) had the anti-Warburg effect activity against colorectal carcinoma. Furthermore, the mechanism for the anti-Warburg effect by RA would be investigated. In our study, we found that RA suppressed glucose consumption and lactate generation in colorectal carcinoma cells; meanwhile, RA inhibited the expression of transcription factor hypoxia-inducible factor-1α (HIF-1α) that affects the glycolytic pathway. Chronic inflammation is a key promoting factor of the Warburg effect. As we supposed, the present study also showed that RA could not only repress proinflammatory cytokines using enzyme-linked immunosorbent assay but it could also suppress microRNAs related to inflammation by real-time PCR. Therefore, we proposed that RA may inhibit the Warburg effect by suppressing the inflammatory response of colorectal carcinoma cells. Recent studies have provided evidence that miR-155 was an important mediator between inflammation and carcinogenesis. We further showed that miR-155 acted to repress the Warburg effect through the mechanism of inactivating the IL-6/STAT3 pathway. Above all, RA might be a potential therapeutic agent against colorectal carcinoma.

  4. ST-Producing E. coli Oppose Carcinogen-Induced Colorectal Tumorigenesis in Mice.

    Science.gov (United States)

    Li, Peng; Lin, Jieru E; Snook, Adam E; Waldman, Scott A

    2017-09-12

    There is a geographic inequality in the incidence of colorectal cancer, lowest in developing countries, and greatest in developed countries. This disparity suggests an environmental contribution to cancer resistance in endemic populations. Enterotoxigenic bacteria associated with diarrheal disease are prevalent in developing countries, including enterotoxigenic E. coli (ETEC) producing heat-stable enterotoxins (STs). STs are peptides that are structurally homologous to paracrine hormones that regulate the intestinal guanylyl cyclase C (GUCY2C) receptor. Beyond secretion, GUCY2C is a tumor suppressor universally silenced by loss of expression of its paracrine hormone during carcinogenesis. Thus, the geographic imbalance in colorectal cancer, in part, may reflect chronic exposure to ST-producing organisms that restore GUCY2C signaling silenced by hormone loss during transformation. Here, mice colonized for 18 weeks with control E. coli or those engineered to secrete ST exhibited normal growth, with comparable weight gain and normal stool water content, without evidence of secretory diarrhea. Enterotoxin-producing, but not control, E. coli, generated ST that activated colonic GUCY2C signaling, cyclic guanosine monophosphate (cGMP) production, and cGMP-dependent protein phosphorylation in colonized mice. Moreover, mice colonized with ST-producing E. coli exhibited a 50% reduction in carcinogen-induced colorectal tumor burden. Thus, chronic colonization with ETEC producing ST could contribute to endemic cancer resistance in developing countries, reinforcing a novel paradigm of colorectal cancer chemoprevention with oral GUCY2C-targeted agents.

  5. ST-Producing E. coli Oppose Carcinogen-Induced Colorectal Tumorigenesis in Mice

    Directory of Open Access Journals (Sweden)

    Peng Li

    2017-09-01

    Full Text Available There is a geographic inequality in the incidence of colorectal cancer, lowest in developing countries, and greatest in developed countries. This disparity suggests an environmental contribution to cancer resistance in endemic populations. Enterotoxigenic bacteria associated with diarrheal disease are prevalent in developing countries, including enterotoxigenic E. coli (ETEC producing heat-stable enterotoxins (STs. STs are peptides that are structurally homologous to paracrine hormones that regulate the intestinal guanylyl cyclase C (GUCY2C receptor. Beyond secretion, GUCY2C is a tumor suppressor universally silenced by loss of expression of its paracrine hormone during carcinogenesis. Thus, the geographic imbalance in colorectal cancer, in part, may reflect chronic exposure to ST-producing organisms that restore GUCY2C signaling silenced by hormone loss during transformation. Here, mice colonized for 18 weeks with control E. coli or those engineered to secrete ST exhibited normal growth, with comparable weight gain and normal stool water content, without evidence of secretory diarrhea. Enterotoxin-producing, but not control, E. coli, generated ST that activated colonic GUCY2C signaling, cyclic guanosine monophosphate (cGMP production, and cGMP-dependent protein phosphorylation in colonized mice. Moreover, mice colonized with ST-producing E. coli exhibited a 50% reduction in carcinogen-induced colorectal tumor burden. Thus, chronic colonization with ETEC producing ST could contribute to endemic cancer resistance in developing countries, reinforcing a novel paradigm of colorectal cancer chemoprevention with oral GUCY2C-targeted agents.

  6. Biomolecular and epidemiological aspects of human papillomavirus induced cervical carcinogenesis

    NARCIS (Netherlands)

    Vermeulen, Christine Frederike Wilhelmine

    2007-01-01

    Cervical cancer remains one of the leading causes of death from cancer among women worldwide. Organised screening programmes aim to trace precursor lesions in order to reduce cervical cancer incidence. Human papillomavirus (HPV) is a necessary cause for cervical carcinogenesis. Most HPV infections

  7. Secondary bile acid-induced dysbiosis promotes intestinal carcinogenesis.

    Science.gov (United States)

    Cao, Hailong; Xu, Mengque; Dong, Wenxiao; Deng, Baoru; Wang, Sinan; Zhang, Yujie; Wang, Shan; Luo, Shenhui; Wang, Weiqiang; Qi, Yanrong; Gao, Jianxin; Cao, Xiaocang; Yan, Fang; Wang, Bangmao

    2017-06-01

    The gut microbiota plays an important role in maintaining intestinal homeostasis. Dysbiosis is associated with intestinal tumorigenesis. Deoxycholic acid (DCA), a secondary bile acid increased by a western diet, correlates with intestinal carcinogenesis. However, evidence relating bile acids, intestinal microbiota and tumorigenesis are limited. In our study, we investigated the effect of DCA on induction of intestinal dysbiosis and its roles in intestinal carcinogenesis. Alteration of the composition of the intestinal microbiota was induced in DCA-treated APCmin/+ mice, which was accompanied by impaired intestinal barrier, gut low grade inflammation and tumor progression. The transfer of fecal microbiota from DCA-treated mice to another group of Apcmin/+ mice increased tumor multiplicity, induced inflammation and recruited M2 phenotype tumor-associated macrophages. Importantly, the fecal microbiota transplantation activated the tumor-associated Wnt/β-catenin signaling pathway. Moreover, microbiota depletion by a cocktail of antibiotics was sufficient to block DCA-induced intestinal carcinogenesis, further suggesting the role of dysbiosis in tumor development. Our study demonstrated that alteration of the microbial community induced by DCA promoted intestinal carcinogenesis. © 2017 UICC.

  8. Hypoxia and cell cycle deregulation in endometrial carcinogenesis

    NARCIS (Netherlands)

    Horrée, N.

    2007-01-01

    Because uterine endometrial carcinoma is the most common malignancy of the female genital tract and 1 of every 5 patients dies of this disease, understanding the mechanisms of carcinogenesis and progression of endometrial carcinoma is important. In general, this thesis can be summarized as a study

  9. Carcinogenesis explained within the context of a theory of organisms.

    Science.gov (United States)

    Sonnenschein, Carlos; Soto, Ana M

    2016-10-01

    For a century, the somatic mutation theory (SMT) has been the prevalent theory to explain carcinogenesis. According to the SMT, cancer is a cellular problem, and thus, the level of organization where it should be studied is the cellular level. Additionally, the SMT proposes that cancer is a problem of the control of cell proliferation and assumes that proliferative quiescence is the default state of cells in metazoa. In 1999, a competing theory, the tissue organization field theory (TOFT), was proposed. In contraposition to the SMT, the TOFT posits that cancer is a tissue-based disease whereby carcinogens (directly) and mutations in the germ-line (indirectly) alter the normal interactions between the diverse components of an organ, such as the stroma and its adjacent epithelium. The TOFT explicitly acknowledges that the default state of all cells is proliferation with variation and motility. When taking into consideration the principle of organization, we posit that carcinogenesis can be explained as a relational problem whereby release of the constraints created by cell interactions and the physical forces generated by cellular agency lead cells within a tissue to regain their default state of proliferation with variation and motility. Within this perspective, what matters both in morphogenesis and carcinogenesis is not only molecules, but also biophysical forces generated by cells and tissues. Herein, we describe how the principles for a theory of organisms apply to the TOFT and thus to the study of carcinogenesis. Copyright © 2016 Elsevier Ltd. All rights reserved.

  10. The dutch surgical colorectal audit

    NARCIS (Netherlands)

    Leersum, N.J. van; Snijders, H.S.; Henneman, D.; Kolfschoten, N.E.; Gooiker, G.A.; Berge, M.G. Ten; Eddes, E.H.; Wouters, M.W.; Tollenaar, R.A.E.M.; Bemelman, W.A.; Dam, R.M. van; Elferink, M.A.; Karsten, T.M.; Krieken, J.H. van; Lemmens, V.E.; Rutten, H.J.; Manusama, E.R.; Velde, C.J. van de; Meijerink, W.J.H.J.; Wiggers, T.; Harst, E. van der; Dekker, J.W.T.; Boerma, D.

    2013-01-01

    INTRODUCTION: In 2009, the nationwide Dutch Surgical Colorectal Audit (DSCA) was initiated by the Association of Surgeons of the Netherlands (ASN) to monitor, evaluate and improve colorectal cancer care. The DSCA is currently widely used as a blueprint for the initiation of other audits, coordinated

  11. The Dutch surgical colorectal audit

    NARCIS (Netherlands)

    van Leersum, N. J.; Snijders, H. S.; Henneman, D.; Kolfschoten, N. E.; Gooiker, G. A.; ten Berge, M. G.; Eddes, E. H.; Wouters, M. W. J. M.; Tollenaar, R. A. E. M.; Bemelman, W. A.; van Dam, R. M.; Elferink, M. A.; Karsten, Th M.; van Krieken, J. H. J. M.; Lemmens, V. E. P. P.; Rutten, H. J. T.; Manusama, E. R.; van de Velde, C. J. H.; Meijerink, W. J. H. J.; Wiggers, Th; van der Harst, E.; Dekker, J. W. T.; Boerma, D.

    2013-01-01

    In 2009, the nationwide Dutch Surgical Colorectal Audit (DSCA) was initiated by the Association of Surgeons of the Netherlands (ASN) to monitor, evaluate and improve colorectal cancer care. The DSCA is currently widely used as a blueprint for the initiation of other audits, coordinated by the Dutch

  12. Gene expression profiling in lymph node-positive and lymph node-negative colorectal cancer.

    Science.gov (United States)

    Kwon, Hyuk-Chan; Kim, Sung-Hyun; Roh, Mee-Sook; Kim, Jae-Seok; Lee, Hyung-Sik; Choi, Hong-Jo; Jeong, Jin-Sook; Kim, Hyo-Jin; Hwang, Tae-Ho

    2004-02-01

    To identify the genes involved in the carcinogenesis and progression of colorectal cancer, we analyzed the gene-expression profiles of colorectal cancer cells from 12 tumors with corresponding noncancerous colonic epithelia using a cDNA microarray representing 4,08 genes. We classified both samples and genes by using a two-way clustering analysis and identified genes that were differentially expressed in the cancerous and noncancerous tissues. Genes associated with lymph node metastasis were identified by means of the supervised learning technique. Differentially expressed genes (77 up-regulated and 45 down-regulated genes) were identified in more than 75 percent of the tumors. The functional categories of these genes belonged to signal transduction (19 percent), metabolism (17 percent), cell structure/motility (14 percent), cell cycle (13 percent), and gene protein expression (13 percent). The gene expression pattern of reverse transcriptase polymerase chain reaction (RT-PCR) results from randomly selected genes shows a pattern similar to that of cDNA microarray. Moreover, the gene expression patterns observed were similar to those reported previously, suggesting rare racial differences. Sixty genes possibly associated with lymph node metastasis in colorectal cancer were selected on the basis of clinicopathological data obtained by performing signal-to-noise calculations. "Leave-one-out" cross-validation testing correctly classified 10 of 12 patients (83.3 percent) as having colorectal cancer with lymph node metastasis vs. those without metastasis. These results provide not only a new molecular basis for understanding the biologic properties of colorectal cancer, including lymph node metastasis, but also provide a resource for future development of therapeutic targets and diagnostic markers for colorectal cancer.

  13. Adiposity factors are not related to the presence of colorectal adenomas

    Directory of Open Access Journals (Sweden)

    Chronis A

    2011-11-01

    Full Text Available Aris Chronis, Konstantinos Thomopoulos, Apostolos Sapountzis, Christos Triantos, Maria Kalafateli, Charalampos Kalofonos, Vassiliki NikolopoulouDepartment of Internal Medicine, Division of Gastroenterology, University Hospital, Patras, GreecePurpose: Adiposity has been thought to be related to colorectal carcinogenesis. The aim of this study was to explore any association between obesity factors and the presence of colorectal adenoma, a potential precancerous lesion.Patients and methods: Two hundred and six consecutive patients undergoing colonoscopy without colorectal cancer were enrolled in the study. Anthropometric measures and other adiposity-related laboratory variables including insulin resistance and serum adiponectin levels were recorded and correlated with the presence of adenoma.Results: Colorectal adenoma was detected in 68/206 patients (33%, tubular adenoma(s in 38 patients, and tubulovillous or villous in 30 patients. Twenty-one patients (10.2% had at least one proximal polyp. The size of the largest adenoma was ≤10 mm in 40 patients and >10 mm in 28 patients. No statistically significant difference was observed in body mass index, waist circumference, fasting plasma glucose concentration, insulin, homeostatic metabolic assessment, cholesterol, low-density lipoproteins, high-density lipoprotein, or triglycerides between patients with and without adenoma. In addition, there was no difference in plasma adiponectin between patients with adenoma (11.1 ± 6 µg/mL and controls (10.2 ± 7.8 µg/mL. Furthermore, no significant difference in any parameter was found between patients with advanced adenoma and no advanced adenoma, nor between patients with proximal or distal tumors.Conclusion: This study found that the presence of colorectal adenoma is not correlated with any adiposity factor. Moreover, obesity does not appear to be associated with the site or the presence of more advanced lesions.Keywords: adiposity, colorectal adenoma

  14. Prevention of Colorectal Cancer by Targeting Obesity-Related Disorders and Inflammation.

    Science.gov (United States)

    Shirakami, Yohei; Ohnishi, Masaya; Sakai, Hiroyasu; Tanaka, Takuji; Shimizu, Masahito

    2017-04-26

    Colorectal cancer is a major healthcare concern worldwide. Many experimental and clinical studies have been conducted to date to discover agents that help in the prevention of this disease. Chronic inflammation in colonic mucosa and obesity, and its related metabolic abnormalities, are considered to increase the risk of colorectal cancer. Therefore, treatments targeting these factors might be a promising strategy to prevent the development of colorectal cancer. Among a number of functional foods, various phytochemicals, including tea catechins, which have anti-inflammatory and anti-obesity properties, and medicinal agents that ameliorate metabolic disorders, might also be beneficial in the prevention of colorectal cancer. In this review article, we summarize the strategies for preventing colorectal cancer by targeting obesity-related disorders and inflammation through nutraceutical and pharmaceutical approaches, and discuss the mechanisms of several phytochemicals and medicinal drugs used in basic and clinical research, especially focusing on the effects of green tea catechins.

  15. Age-specific incidence of all neoplasms after colorectal cancer.

    Science.gov (United States)

    Levi, Fabio; Randimbison, Lalao; Blanc-Moya, Rafael; La Vecchia, Carlo

    2014-10-01

    Patients diagnosed with a specific neoplasm tend to have a subsequent excess risk of the same neoplasm. The age incidence of a second neoplasm at the same site is approximately constant with age, and consequently the relative risk is greater at younger age. It is unclear whether such a line of reasoning can be extended from a specific neoplasm to the incidence of all neoplasms in subjects diagnosed with a defined neoplasm. We considered the age-specific incidence of all non-hormone-related epithelial neoplasms after a first primary colorectal cancer (n = 9542) in the Vaud Cancer Registry data set. In subjects with a previous colorectal cancer, the incidence rate of all other epithelial non-hormone-related cancers was stable around 800 per 100,000 between age 30 and 60 years, and rose only about twofold to reach 1685 at age 70 to 79 years and 1826 per 100,000 at age 80 years or older. After excluding synchronous cancers, the rise was only about 1.5-fold, that is, from about 700 to 1000. In the general population, the incidence rate of all epithelial non-hormone-related cancers was 29 per 100,000 at age 30 to 39 years, and rose 30-fold to 883 per 100,000 at age 70 to 79 years. Excluding colorectal cancers, the rise of all non-hormone-related cancers was from 360 per 100,000 at age 40 to 49 years to 940 at age 70 to 79 years after colorectal cancer, and from 90 to 636 per 100,000 in the general population (i.e., 2.6- vs. 7.1-fold). The rise of incidence with age of all epithelial non-hormone-related second cancers after colorectal cancer is much smaller than in the general population. This can possibly be related to the occurrence of a single mutational event in a population of susceptible individuals, although alternative models are plausible within the complexity of the process of carcinogenesis. Copyright © 2014 Elsevier Inc. All rights reserved.

  16. Progressive increase of matrix metalloprotease-9 and interleukin-8 serum levels during carcinogenic process in human colorectal tract.

    Directory of Open Access Journals (Sweden)

    Fiorella Biasi

    Full Text Available BACKGROUND: Inflammatory reactions, known to promote tumor growth and invasion, have been found associated with colorectal carcinoma (CRC. Macrophages are the chief component of the inflammatory infiltration that occurs early in the progression from non-invasive to malignant tumor, with a switch from the pro-inflammatory phenotype to the tumor-promoting phenotype. Tumor and stroma are additional sources of inflammation-related molecules. The study aimed to evaluate, during colorectal carcinogenesis from benign to malignant phases: i the trend of serum levels of IL-8, IL-6, TGFβ1, VEGF and MMPs; ii the parallel trend of CRP serum levels; iii derangement of the principal TGFβ1 receptors (TGFβ1RI/RII in tumor tissues. METHODOLOGY/PRINCIPAL FINDINGS: 96 patients with colon adenomas or CRC at different stages of progression, and 17 controls, were recruited. Serum IL-8, IL-6, TGFβ1, VEGF, MMPs and CRP levels were analyzed before endoscopy or surgery. TGFβ1 receptors were evaluated in adenoma biopsies and surgically-removed colorectal adenocarcinomas. Serum levels of IL-8 in adenocarcinoma patients were increased from stage II, when also the enzymatic activity of MMP-9 increased. Of note, the increasing trend of the two serum markers was found significantly correlated. Trend of serum CRP was also very similar to that of IL-8 and MMP-9, but just below statistical significance. TGFβ1 levels were lower at stage III CRC, while IL-6 and VEGF levels had no significant variations. In tissue specimens, TGFβ1 receptors were already absent in about 50% of adenomas, and this percentage of missing receptors markedly increased in CRC stages III and IV. CONCLUSIONS: Combined quantification of serum IL-8, MMP-9 and CRP, appears a reliable and advanced index of inflammation-related processes during malignant phase of colorectal carcinogenesis, since these molecules remain within normal range in colorectal adenoma bearing patients, while consistently increase in

  17. MicroRNA, HPV AND CERVICAL CARCINOGENESIS: MOLECULAR ASPECTS AND PROSPECTS OF CLINICAL APPLICATION

    Directory of Open Access Journals (Sweden)

    P. A. Arkhangelskaya

    2016-01-01

    Full Text Available Cervical cancer is one of the most common cancers of the female reproductive system and a leading cause of mortality in women worldwide. Epidemiologic and experimental data have clearly demonstrated a causal role of Human Papillomavirus in cervical carcinogenesis. Determination of HPV DNA of high carcinogenic risk is relevant screening tool to identify patients with an increased risk of cervical neoplasia. However, the positive predictive value of such an analysis is not high enough. Analysis of additional indicators of infection (viral load, the ratio of episomal and integrated forms of the virus, the duration of its persistence can be used to improve the diagnostic and prognostic value of HPV testing. In the last decade, studies have shown that HPV induces specific changes in miRNA profile of the infected cell, which reflect the phasing of the disease and may have diagnostic / prognostic value. This review summarizes the current understanding of cellular changes in the profile of microRNAs, caused by infection with HPV, given the known examples of microRNA involvement in cervical carcinogenesis and the perspectives of the possible use of microRNAs as biomarkers in the diagnosis of cervical cancer.

  18. Influence of chronic moderate sleep restriction and exercise on inflammation and carcinogenesis in mice.

    Science.gov (United States)

    Zielinski, Mark R; Davis, J Mark; Fadel, James R; Youngstedt, Shawn D

    2012-05-01

    The effects of chronic moderate sleep restriction and exercise training on carcinogenesis were examined in adenomatous polyposis coli multiple intestinal neoplasma (APC Min(+/-)) mice, a genetic strain which is predisposed to developing adenomatous polyposis. The mice were randomized to one of four 11 week treatments in a 2×2 design involving sleep restriction (by 4 h/day) vs. normal sleep and exercise training (1h/day) vs. sedentary control. Wild-type control mice underwent identical experimental treatments. Compared with the wild-type mice, APC Min(+/-) mice had disrupted hematology and enhanced pro-inflammatory cytokine production from peritoneal exudate cells. Among the APC Min(+/-) mice, consistent interactions of sleep loss and exercise were found for measures of polyp formation, inflammation, and hematology. Sleep loss had little effect on these variables under sedentary conditions, but sleep loss had clear detrimental effects under exercise conditions. Exercise training resulted in improvements in these measures under normal sleep conditions, but exercise tended to elicit no effect or to exacerbate the effects of sleep restriction. Significant correlations of inflammation with polyp burden were observed. Among wild-type mice, similar, but less consistent interactions of sleep restriction and exercise were found. These data suggest that the benefits of exercise on carcinogenesis and immune function were impaired by chronic moderate sleep restriction, and that harmful effects of sleep restriction were generally realized only in the presence of exercise. Published by Elsevier Inc.

  19. Metastatic paediatric colorectal carcinoma.

    LENUS (Irish Health Repository)

    Woods, R

    2012-03-01

    A 16-year-old girl presented to our unit with crampy abdominal pain, change in bowel habit, a subjective impression of weight loss and a single episode of haematochezia. She was found to have a rectosigmoid adenocarcinoma and proceeded to laparoscopic anterior resection, whereupon peritoneal metastases were discovered. She received chemotherapy and is alive and well ten month later with no radiological evidence of disease. Colorectal carcinoma is rare in the paediatric population but is increasing in incidence. Early diagnosis is critical to enable optimal outcomes.

  20. [Genetics of colorectal cancer].

    Science.gov (United States)

    Balaguer, Francesc

    2013-10-01

    Up to 5% of all cases of colorectal cancer (CRC) are due to a known hereditary syndrome. These hereditary forms often require a high degree of suspicion for their diagnosis and specific and specialized management. Moreover, a diagnosis of hereditary CRC has important consequences, not only for patients-for whom highly effective preventive measures are available-, but also for their relatives, who may be carriers of the same condition. The most significant advances in the field of hereditary CRC have been produced in the diagnosis and characterization of these syndromes and in the discovery of new causative genes. Copyright © 2013 Elsevier España, S.L. All rights reserved.

  1. [Epigenetics and colorectal cancer].

    Science.gov (United States)

    Menéndez, Pablo; Villarejo, Pedro; Padilla, David; Menéndez, José María; Rodríguez Montes, José Antonio

    2012-05-01

    The epigenetic and physiological mechanisms that alter the structure of chromatin include the methylation of DNA, changes in the histones, and changes in RNA. A literature review has been carried out using PubMed on the evidence published on the association between epigenetics and colorectal cancer. The scientific literature shows that epigenetic changes, such as genetic modifications may be very significant in the origin of neoplastic disease, contributing both to the development and progression of the disease. Copyright © 2011 AEC. Published by Elsevier Espana. All rights reserved.

  2. Repeated anastomotic recurrence of colorectal tumors: Genetic analysis of two cases

    Science.gov (United States)

    Costi, Renato; Azzoni, Cinzia; Marchesi, Federico; Bottarelli, Lorena; Violi, Vincenzo; Bordi, Cesare

    2011-01-01

    AIM: To investigate genetics of two cases of colorectal tumor local recurrence and throw some light on the etiopathogenesis of anastomotic recurrence. METHODS: Two cases are presented: a 65-year-old female receiving two colonic resections for primary anastomotic recurrences within 21 mo, and a 57-year-old female undergoing two local excisions of recurrent anastomotic adenomas within 26 mo. A loss of heterozygosity (LOH) study of 25 microsatellite markers and a mutational analysis of genes BRAF, K-RAS and APC were performed in samples of neoplastic and normal colonic mucosa collected over the years. RESULTS: A diffuse genetic instability was present in all samples, including neoplastic and normal colonic mucosa. Two different patterns of genetic alterations (LOH at 5q21 and 18p11.23 in the first case, and LOH at 1p34 and 3p14 in the second) were found to be associated with carcinogenesis over the years. A role for the genes MYC-L (mapping at 1p34) and FIHT (mapping at 3p14.2) is suggested, whereas a role for APC (mapping at 5q21) is not shown. CONCLUSION: The study challenges the most credited intraluminal implantation and metachronous carcinogenesis theories, and suggests a persistent, patient-specific alteration as the trigger of colorectal cancer anastomotic recurrence. PMID:21990958

  3. Opportunistic intestinal infections and risk of colorectal cancer among people with AIDS.

    Science.gov (United States)

    Shebl, Fatma M; Engels, Eric A; Goedert, James J

    2012-09-01

    Because mucosal inflammation contributes to colorectal carcinogenesis, we studied the impact of intestinal infections on risk of this malignancy among people with AIDS (PWA). Using the population-based HIV/AIDS Cancer Match, which includes approximately half of all PWA in the United States, the cancer registries ascertained colorectal cancers (ICD-O3 codes C180-C189, C199, C209, and C260). During 4-120 months after AIDS onset, risk of cancer occurring after AIDS-defining intestinal infections (considered as time-dependent exposures) was estimated with hazard ratios (HR) and 95% confidence intervals (CI) calculated by Cox regression. Analyses included cancers overall and by histology and anatomic site. After excluding 118 squamous cell rectal cancers (possible anal cancers), we analyzed 320 incident colorectal cancer cases that occurred among 471,909 PWA. Colorectal cancer risk was marginally elevated following cryptosporidiosis (HR=2.08, 95% CI=0.93-4.70, p=0.08) and mucocutaneous herpes (HR=1.69, 95% CI=0.97-2.95, p=0.07) but not with Pneumocystis pneumonia (HR=0.79, 95% CI=0.57-1.10). Cryptosporidiosis was associated with rare colon squamous cell carcinoma [N=8, HR=13, 95% CI=1.5-110] and uncommon histologies [HR=4.4, 95% CI=1.1-18, p=0.04], but it was not associated with colorectal adenocarcinoma (N=269, HR=1.3, 95% CI=0.4-3.9, p=0.70). Mucocutaneous herpes was associated with colon squamous cell carcinoma (HR=13, 95% CI=2.4-67, p=0.003) but not with colorectal adenocarcinoma (HR=1.3, 95% CI=0.6-2.6, p=0.52) or uncommon histologies (HR=2.5, 95% CI=0.8-8.2, p=0.13). Colon squamous cell carcinoma risk was significantly elevated among PWA who had cryptosporidiosis or mucocutaneous herpes. These findings might suggest that HPV or inflammation from other infection may contribute to carcinogenesis.

  4. Primary Prevention of Colorectal Cancer

    Science.gov (United States)

    Chan, Andrew T.; Giovannucci, Edward L.

    2010-01-01

    Colorectal cancer has been strongly associated with a Western lifestyle. In the past several decades, much has been learned about the dietary, lifestyle, and medication risk factors for this malignancy. Although there is controversy about the role of specific nutritional factors, consideration of the dietary pattern as a whole appears useful for formulating recommendations. For example, several studies have shown that high intake of red and processed meats, highly refined grains and starches, and sugars is related to increased risk of colorectal cancer. Replacing these factors with poultry, fish, and plant sources as the primary source of protein; unsaturated fats as the primary source of fat; and unrefined grains, legumes and fruits as the primary source of carbohydrates is likely to lower risk of colorectal cancer. Although a role for supplements, including vitamin D, folate, and vitamin B6, remains uncertain, calcium supplementation is likely to be at least modestly beneficial. With respect to lifestyle, compelling evidence indicates that avoidance of smoking and heavy alcohol use, prevention of weight gain, and the maintenance of a reasonable level of physical activity are associated with markedly lower risks of colorectal cancer. Medications such as aspirin and non-steroidal anti-inflammatory drugs and post-menopausal hormones for women are associated with significant reductions in colorectal cancer risk, though their utility is affected by associated risks. Taken together, modifications in diet and lifestyle should substantially reduce the risk of colorectal cancer and could complement screening in reducing colorectal cancer incidence. PMID:20420944

  5. Diet, gender, and colorectal neoplasia.

    Science.gov (United States)

    Jacobs, Elizabeth T; Thompson, Patricia A; Martínez, María Elena

    2007-09-01

    The association between diet and colorectal cancer has been studied in depth for many decades, with equivocal results. It has been hypothesized that cancers arising in the distal and proximal colon have different pathologies, and therefore different risk factors. As such, it is possible that diet-related factors might influence colorectal neoplasia differently depending on the subsite. Recent evidence indicates that women may be more likely to develop proximal cancers than men. Additionally, the link between certain dietary factors and colorectal neoplasia in women seems to vary by menopausal status. Given these observations, women may be affected differently than men by diet-related factors. The objective of this article was therefore to review the data for diet and colorectal adenomas and cancer, and then attempt to address the potential differences in the association of diet-related factors and colorectal neoplasia in men and women. For total energy intake, selenium, and fiber, it seems that there may be slightly stronger effects in men as compared with women, whereas calcium and folate seem to affect both sexes similarly. With regard to vitamin D and colorectal cancer, women may exhibit stronger associations than men. Perhaps the most evidence for a sex-specific effect is observed for obesity, where more substantial direct relationships between body size and colorectal neoplasia have been reported for men than for women. However, this observation may be influenced by the differential effects in women by menopausal status. Further research on sex-specific dietary effects is warranted.

  6. miRNA-26b Overexpression in Ulcerative Colitis-associated Carcinogenesis.

    Science.gov (United States)

    Benderska, Natalya; Dittrich, Anna-Lena; Knaup, Sabine; Rau, Tilman T; Neufert, Clemens; Wach, Sven; Fahlbusch, Fabian B; Rauh, Manfred; Wirtz, Ralph M; Agaimy, Abbas; Srinivasan, Swetha; Mahadevan, Vijayalakshmi; Rümmele, Petra; Rapti, Emmanouela; Gazouli, Maria; Hartmann, Arndt; Schneider-Stock, Regine

    2015-09-01

    Longstanding ulcerative colitis (UC) bears a high risk for development of UC-associated colorectal carcinoma (UCC). The inflammatory microenvironment influences microRNA expression, which in turn deregulates target gene expression. microRNA-26b (miR-26b) was shown to be instrumental in normal tissue growth and differentiation. Thus, we aimed to investigate the impact of miR-26b in inflammation-associated colorectal carcinogenesis. Two different cohorts of patients were investigated. In the retrospective group, a tissue microarray with 38 samples from 17 UC/UCC patients was used for miR-26b in situ hybridization and quantitative reverse transcription polymerase chain reaction analyses. In the prospective group, we investigated miR-26b expression in 25 fresh-frozen colon biopsies and corresponding serum samples of 6 UC and 15 non-UC patients, respectively. In silico analysis, Ago2-RNA immunoprecipitation, luciferase reporter assay, quantitative reverse transcription polymerase chain reaction examination, and miR-26b mimic overexpression were employed for target validation. miR-26b expression was shown to be upregulated with disease progression in tissues and serum of UC and UCC patients. Using miR-26b and Ki-67 expression levels, an UCC was predicted with high accuracy. We identified 4 novel miR-26b targets (DIP1, MDM2, CREBBP, BRCA1). Among them, the downregulation of the E3 ubiquitin ligase DIP1 was closely related to death-associated protein kinase stabilization along the normal mucosa-UC-UCC sequence. In silico functional pathway analysis revealed that the common cellular pathways affected by miR-26b are highly related to cancerogenesis and the development of gastrointestinal diseases. We suggest that miR-26b could serve as a biomarker for inflammation-associated processes in the gastrointestinal system. Because miR-26b expression is downregulated in sporadic colon cancer, it could discriminate between UCC and the sporadic cancer type.

  7. Social media in colorectal surgery.

    Science.gov (United States)

    Wexner, S D; Petrucci, A M; Brady, R R; Ennis-O'Connor, M; Fitzgerald, J E; Mayol, J

    2017-02-01

    The engagement of social media in healthcare continues to expand. For members of the colorectal community, social media has already made a significant impact on practice, education and patient care. The applications are unique such that they provide a platform for instant communication and information sharing with other users worldwide. The purpose of this article is to provide an overview of how social media has the potential to change clinical practice, training, research and patient care in colorectal surgery. Colorectal Disease © 2016 The Association of Coloproctology of Great Britain and Ireland.

  8. [Hereditary and familial colorectal cancer].

    Science.gov (United States)

    Balaguer, Francesc

    2014-09-01

    Up to 5% of all colorectal cancer cases are caused by a known hereditary syndrome. These hereditary types often need a higher degree of clinical suspicion to be diagnosed and require specific and specialized management. In addition, diagnosing hereditary colorectal cancer has significant consequences not only for the patient, for whom there are effective preventative measures, but also for their families, who could be carriers of the condition. The most significant advances in the field of colorectal cancer have come from the diagnosis and characterization of these syndromes. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

  9. Pathogenesis and biomarkers of carcinogenesis in ulcerative colitis

    DEFF Research Database (Denmark)

    Thorsteinsdottir, Sigrun; Gudjonsson, Thorkell; Nielsen, Ole Haagen

    2011-01-01

    One of the most serious complications of ulcerative colitis is the development of colorectal cancer. Screening patients with ulcerative colitis by standard histological examination of random intestinal biopsy samples might be inefficient as a method of cancer surveillance. This Review focuses...... on the current understanding of the pathogenesis of ulcerative colitis-associated colorectal cancer and how this knowledge can be transferred into patient management to assist clinicians and pathologists in identifying patients with ulcerative colitis who have an increased risk of colorectal cancer. Inflammation......-driven mechanisms of DNA damage, including the generation and effects of reactive oxygen species, microsatellite instability, telomere shortening and chromosomal instability, are reviewed, as are the molecular responses to genomic stress. We also discuss how these mechanisms can be translated into usable biomarkers...

  10. Genome-Wide Screening of Genes Showing Altered Expression in Liver Metastases of Human Colorectal Cancers by cDNA Microarray

    Directory of Open Access Journals (Sweden)

    Rempei Yanagawa

    2001-01-01

    Full Text Available In spite of intensive and increasingly successful attempts to determine the multiple steps involved in colorectal carcinogenesis, the mechanisms responsible for metastasis of colorectal tumors to the liver remain to be clarified. To identify genes that are candidates for involvement in the metastatic process, we analyzed genome-wide expression profiles of 10 primary colorectal cancers and their corresponding metastatic lesions by means of a cDNA microarray consisting of 9121 human genes. This analysis identified 40 genes whose expression was commonly upregulated in metastatic lesions, and 7 that were commonly downregulated. The upregulated genes encoded proteins involved in cell adhesion, or remodeling of the actin cytoskeleton. Investigation of the functions of more of the altered genes should improve our understanding of metastasis and may identify diagnostic markers and/or novel molecular targets for prevention or therapy of metastatic lesions.

  11. Epigenetics in metal carcinogenesis: nickel, arsenic, chromium and cadmium.

    Science.gov (United States)

    Arita, Adriana; Costa, Max

    2009-01-01

    Although carcinogenic metals have been known to disrupt a wide range of cellular processes the precise mechanism by which these exert their carcinogenic effects is not known. Over the last decade or two, studies in the field of metal carcinogenesis suggest that epigenetic mechanisms may play a role in metal-induced carcinogenesis. In this review we summarize the evidence demonstrating that exposure to carcinogenic metals such as nickel, arsenic, chromium, and cadmium can perturb DNA methylation levels as well as global and gene specific histone tail posttranslational modification marks. We also wish to emphasize the importance in understanding that gene expression can be regulated by both genetic and epigenetic mechanisms and both these must be considered when studying the mechanism underlying the toxicity and cell-transforming ability of carcinogenic metals and other toxicants, and aberrant changes in gene expression that occur during disease states such as cancer.

  12. Cervical Carcinogenesis and Immune Response Gene Polymorphisms: A Review

    Directory of Open Access Journals (Sweden)

    Akash M. Mehta

    2017-01-01

    Full Text Available The local immune response is considered a key determinant in cervical carcinogenesis after persistent infection with oncogenic, high-risk human papillomavirus (HPV infections. Genetic variation in various immune response genes has been shown to influence risk of developing cervical cancer, as well as progression and survival among cervical cancer patients. We reviewed the literature on associations of immunogenetic single nucleotide polymorphism, allele, genotype, and haplotype distributions with risk and progression of cervical cancer. Studies on HLA and KIR gene polymorphisms were excluded due to the abundance on literature on that subject. We show that multiple genes and loci are associated with variation in risk of cervical cancer. Rather than one single gene being responsible for cervical carcinogenesis, we postulate that variations in the different immune response genes lead to subtle differences in the effectiveness of the antiviral and antitumour immune responses, ultimately leading to differences in risk of developing cervical cancer and progressive disease after HPV infection.

  13. The Role of Ubiquitine Proteasome Pathway in Carcinogenesis

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    N.Ceren Sumer Turanligil

    2010-02-01

    Full Text Available Ubiquitin works as a marker protein which targets misfolded or injured proteins to cellular degradation. It brings the abnormal proteins to a subcellular organelle named proteasome and it maintains the degradation of proteins in limited lenghts of peptides by leaving the process withuout being changed. Mistakes in ubiquitin-dependent proteolysis in various steps of carcinogenesis is known. In this review, we dealed with the effects of ubiquitin-proteasome pathway (UPP on carcinogenesis via intercellular signaling molecules like Ras, transcription factors like NF-kB, cytokines like TNF-alfa Tumor necrosis factor, protooncogenes like p53 and MDM2(murine double minute 2, components of cell cycle and DNA repair proteins like BRCA1. We also focused on the relationship of UPP on antigen presentation which is active in immune response and its place in the aetiology of colon cancer to provide a specific example. [Archives Medical Review Journal 2010; 19(1.000: 36-55

  14. Effects of dietary beef, pork, chicken and salmon on intestinal carcinogenesis in A/J Min/+ mice.

    Directory of Open Access Journals (Sweden)

    Christina Steppeler

    Full Text Available The International Agency for Research on Cancer has classified red meat as "probably carcinogenic to humans" (Group 2A. In mechanistic studies exploring the link between intake of red meat and CRC, heme iron, the pigment of red meat, is proposed to play a central role as a catalyzer of luminal lipid peroxidation and cytotoxicity. In the present work, the novel A/J Min/+ mouse was used to investigate the effects of dietary beef, pork, chicken, or salmon (40% muscle food (dry weight and 60% powder diet on Apc-driven intestinal carcinogenesis, from week 3-13 of age. Muscle food diets did not differentially affect carcinogenesis in the colon (flat ACF and tumors. In the small intestine, salmon intake resulted in a lower tumor size and load than did meat from terrestrial animals (beef, pork or chicken, while no differences were observed between the effects of white meat (chicken and red meat (pork and beef. Additional results indicated that intestinal carcinogenesis was not related to dietary n-6 polyunsaturated fatty acids, intestinal formation of lipid peroxidation products (thiobarbituric acid reactive substances, TBARS, or cytotoxic effects of fecal water on Apc-/+ cells. Notably, the amount of heme reaching the colon appeared to be relatively low in this study. The greatest tumor load was induced by the reference diet RM1, underlining the importance of the basic diets in experimental CRC. The present study in A/J Min/+ mice does not support the hypothesis of a role of red meat in intestinal carcinogenesis.

  15. Effects of dietary beef, pork, chicken and salmon on intestinal carcinogenesis in A/J Min/+ mice

    Science.gov (United States)

    Sødring, Marianne; Egelandsdal, Bjørg; Kirkhus, Bente; Oostindjer, Marije; Alvseike, Ole; Gangsei, Lars Erik; Hovland, Ellen-Margrethe; Pierre, Fabrice; Paulsen, Jan Erik

    2017-01-01

    The International Agency for Research on Cancer has classified red meat as “probably carcinogenic to humans” (Group 2A). In mechanistic studies exploring the link between intake of red meat and CRC, heme iron, the pigment of red meat, is proposed to play a central role as a catalyzer of luminal lipid peroxidation and cytotoxicity. In the present work, the novel A/J Min/+ mouse was used to investigate the effects of dietary beef, pork, chicken, or salmon (40% muscle food (dry weight) and 60% powder diet) on Apc-driven intestinal carcinogenesis, from week 3–13 of age. Muscle food diets did not differentially affect carcinogenesis in the colon (flat ACF and tumors). In the small intestine, salmon intake resulted in a lower tumor size and load than did meat from terrestrial animals (beef, pork or chicken), while no differences were observed between the effects of white meat (chicken) and red meat (pork and beef). Additional results indicated that intestinal carcinogenesis was not related to dietary n-6 polyunsaturated fatty acids, intestinal formation of lipid peroxidation products (thiobarbituric acid reactive substances, TBARS), or cytotoxic effects of fecal water on Apc-/+ cells. Notably, the amount of heme reaching the colon appeared to be relatively low in this study. The greatest tumor load was induced by the reference diet RM1, underlining the importance of the basic diets in experimental CRC. The present study in A/J Min/+ mice does not support the hypothesis of a role of red meat in intestinal carcinogenesis. PMID:28426718

  16. Synergistic chemopreventive effects of nobiletin and atorvastatin on colon carcinogenesis.

    Science.gov (United States)

    Wu, Xian; Song, Mingyue; Qiu, Peiju; Rakariyatham, Kanyasiri; Li, Fang; Gao, Zili; Cai, Xiaokun; Wang, Minqi; Xu, Fei; Zheng, Jinkai; Xiao, Hang

    2017-04-01

    Different cancer chemopreventive agents may act synergistically and their combination may produce enhanced protective effects against carcinogenesis than each individual agent alone. Herein, we investigated the chemopreventive effects of nobiletin (NBT, a citrus polymethoxyflavone) and atorvastatin (ATST, a lipid-lowering drug) in colon cancer cells/macrophages and an azoxymethane (AOM)-induced colon carcinogenesis rat model. The results demonstrated that co-treatments of NBT/ATST produced enhanced growth inhibitory and anti-inflammatory effects on the colon cancer cells and macrophages, respectively. Isobologram analysis confirmed that these interactions between NBT and ATST were synergistic. NBT/ATST co-treatment also synergistically induced extensive cell cycle arrest and apoptosis in colon cancer cells. Oral administration of NBT (0.1%, w/w in diet) or ATST (0.04%, w/w in diet) significantly decreased colonic tumor incidence and multiplicity in AOM-treated rats. Most importantly, co-treatment of NBT/ATST at their half doses (0.05% NBT + 0.02% ATST, w/w in diet) resulted in even stronger inhibitory effects on colonic tumor incidence and multiplicity than did NBT or ATST alone at higher doses. Statistical analysis confirmed that the enhanced chemopreventive activities against colon carcinogenesis in rats by the NBT/ATST combination were highly synergistic. Our results further demonstrated that NBT/ATST co-treatment profoundly modulated key cellular signaling regulators associated with inflammation, cell proliferation, cell cycle progression, apoptosis, angiogenesis and metastasis in the colon of AOM-treated rats. In conclusion, for the first time, our results demonstrated a strong synergy in inhibiting colon carcinogenesis produced by the co-treatment of NBT and ATST, which provided a scientific basis for using NBT in combination with ATST for colon cancer chemoprevention in humans. © The Author 2017. Published by Oxford University Press. All rights reserved

  17. Effect of Dendrobium officinale Extraction on Gastric Carcinogenesis in Rats

    OpenAIRE

    Yi Zhao; Yan Liu; Xi-Ming Lan; Guo-Liang Xu; You-Zhi Sun; Fei Li; Hong-Ning Liu

    2016-01-01

    Dendrobium officinale (Tie Pi Shi Hu in Chinese) has been widely used to treat different diseases in China. Anticancer effect is one of the important effects of Dendrobium officinale. However, the molecular mechanism of its anticancer effect remains unclear. In the present study, gastric carcinogenesis in rats was used to evaluate the effect of Dendrobium officinale on cancer, and its pharmacological mechanism was explored. Dendrobium officinale extracts (4.8 and 2.4 g/kg) were orally adminis...

  18. Rapidly resorbable vs. non-resorbable suture for experimental colonic anastomoses in rats--a randomized experimental study

    DEFF Research Database (Denmark)

    Klein, Mads; Pommergaard, Hans-Christian; Gögenur, Ismail

    2011-01-01

    Anastomotic dehiscence remains an important challenge for colorectal surgeons worldwide. Extensive research focused on performing a safe anastomosis is conducted with rats being the most used model when examining colorectal anastomoses. In daily clinical practice resorbable sutures are used when...... hand-sewn anastomoses are performed. However, in the experimental studies examining colorectal anastomoses, non-resorbable sutures have predominantly been used. The aim of this study was to compare a rapidly resorbable suture with a non-resorbable suture in experimental colorectal anastomoses....

  19. Carcinogenesis and diabetic wound healing: evidences of parallelism.

    Science.gov (United States)

    Singh, Kanhaiya; Singh, Kiran

    2015-01-01

    There is a close association of chronic tissue damage, inflammation and cancer. A chronic injury may contribute to sustained healing response leading to fibrosis, organ failure and carcinogenesis. Wounds created due to mechanical or patho-physiological insults, generally follow a sophisticated series of mutually coherent steps leading to the re-establishment of the affected tissue or organ. The process of wound healing resembles fundamental processes like embryogenesis and tissue regeneration. All the stages in the wound healing process are tightly regulated and any sort of imbalance may lead to either non healing chronic ulcers or excessively healed hypertrophic scars. Diabetic wounds are also very tough to heal and in many cases they do not heal, ultimately resulting in the amputation of that body part. The non-healing property of diabetic wounds may be due to combined effect of intrinsic and extrinsic factors. In this review, we aimed to explore the steps involved in diabetic wound healing and compare it with the process of carcinogenesis. This review demonstrates that both carcinogenesis and the diabetic wound healing follow a similar path of latent healing in an abnormal exaggerated manner.

  20. Roles of stem cells in tissue turnover and radiation carcinogenesis.

    Science.gov (United States)

    Niwa, Ohtsura

    2010-12-01

    Radiation research has its foundation on the target and hit theories, which assume that the initial stochastic deposition of energy on a sensitive target in a cell determines the final biological outcome. This assumption is rather static in nature but forms the foundation of the linear no-threshold (LNT) model of radiation carcinogenesis. The stochastic treatment of radiation carcinogenesis by the LNT model enables easy calculation of radiation risk, and this has made the LNT model an indispensable tool for radiation protection. However, the LNT model sometimes fails to explain some of the biological and epidemiological data, and this suggests the need for insight into the mechanisms of radiation carcinogenesis. Recent studies have identified unique characteristics of the tissue stem cells and their roles in tissue turnover. In the present report, some important issues of radiation protection such as the risk of low-dose-rate exposures and in utero exposures are discussed in light of the recent advances of stem cell biology.

  1. Alterations of Histone H1 Phosphorylation During Bladder Carcinogenesis

    Science.gov (United States)

    Telu, Kelly H.; Abbaoui, Besma; Thomas-Ahner, Jennifer M.; Zynger, Debra L.; Clinton, Steven K.

    2013-01-01

    There is a crucial need for development of prognostic and predictive biomarkers in human bladder carcinogenesis in order to personalize preventive and therapeutic strategies and improve outcomes. Epigenetic alterations, such as histone modifications, are implicated in the genetic dysregulation that is fundamental to carcinogenesis. Here we focus on profiling the histone modifications during the progression of bladder cancer. Histones were extracted from normal human bladder epithelial cells, an immortalized human bladder epithelial cell line (hTERT), and four human bladder cancer cell lines (RT4, J82, T24, and UMUC3) ranging from superficial low-grade to invasive high-grade cancers. Liquid Chromatography-Mass Spectrometry (LC-MS) profiling revealed a statistically significant increase in phosphorylation of H1 linker histones from normal human bladder epithelial cells to low-grade superficial to high-grade invasive bladder cancer cells. This finding was further validated by immunohistochemical staining of the normal epithelium and transitional cell cancer from human bladders. Cell cycle analysis of histone H1 phosphorylation by western blotting showed an increase of phosphorylation from G0/G1 phase to M phase, again supporting this as a proliferative marker. Changes in histone H1 phosphorylation status may further clarify epigenetic changes during bladder carcinogenesis and provide diagnostic and prognostic biomarkers or targets for future therapeutic interventions. PMID:23675690

  2. Blueberry husks and probiotics attenuate colorectal inflammation and oncogenesis, and liver injuries in rats exposed to cycling DSS-treatment.

    Directory of Open Access Journals (Sweden)

    Asa Håkansson

    Full Text Available Long-term colonic inflammation promotes carcinogenesis and histological abnormalities of the liver, and colorectal tumours frequently arise in a background of dysplasia, a precursor of adenomas. Altered colonic microbiota with an increased proportion of bacteria with pro-inflammatory characteristics, have been implicated in neoplastic progression. The composition of the microbiota can be modified by dietary components such as probiotics, polyphenols and dietary fibres. In the present study, the influence of probiotics in combination with blueberry husks on colorectal carcinogenesis and subsequent liver damage was evaluated.Colorectal tumours were induced in rats by cyclic treatment with dextran sulphate sodium (DSS. Blueberry husks and a mixture of three probiotic strains (Bifidobacterium infantis DSM 15159, Lactobacillus gasseri, DSM 16737 and Lactobacillus plantarum DSM 15313 supplemented a basic diet fortified with oats. The condition of the rats was monitored using a disease activity index (DAI. A qualitative and quantitative histological judgement was performed on segments of distal colon and rectum and the caudate lobe of the liver. The formation of short-chain fatty acids, bacterial translocation, the inflammatory reaction and viable count of lactobacilli and Enterobaceriaceae were addressed.Blueberry husks with or without probiotics significantly decreased DAI, and significantly reduced the number of colonic ulcers and dysplastic lesions. With a decreased proportion of blueberry husk in the diet, the probiotic supplement was needed to achieve a significant decrease in numbers of dysplastic lesions. Probiotics decreased faecal viable count of Enterobacteriaceae and increased that of lactobacilli. Blueberry husks with or without probiotics lowered the proportion of butyric acid in distal colon, and decreased the haptoglobin levels. Probiotics mitigated hepatic injuries by decreasing parenchymal infiltration and the incidence of stasis and

  3. Danish Colorectal Cancer Group Database

    DEFF Research Database (Denmark)

    Ingeholm, Peter; Gögenur, Ismail; Iversen, Lene H

    2016-01-01

    AIM OF DATABASE: The aim of the database, which has existed for registration of all patients with colorectal cancer in Denmark since 2001, is to improve the prognosis for this patient group. STUDY POPULATION: All Danish patients with newly diagnosed colorectal cancer who are either diagnosed......, and other pathological risk factors. DESCRIPTIVE DATA: The database has had >95% completeness in including patients with colorectal adenocarcinoma with >54,000 patients registered so far with approximately one-third rectal cancers and two-third colon cancers and an overrepresentation of men among rectal...... diagnosis, surgical interventions, and short-term outcomes. The database does not have high-resolution oncological data and does not register recurrences after primary surgery. The Danish Colorectal Cancer Group provides high-quality data and has been documenting an increase in short- and long...

  4. Lysyl oxidase in colorectal cancer.

    Science.gov (United States)

    Cox, Thomas R; Erler, Janine T

    2013-11-15

    Colorectal cancer is the third most prevalent form of cancer worldwide and fourth-leading cause of cancer-related mortality, leading to ~600,000 deaths annually, predominantly affecting the developed world. Lysyl oxidase is a secreted, extracellular matrix-modifying enzyme previously suggested to act as a tumor suppressor in colorectal cancer. However, emerging evidence has rapidly implicated lysyl oxidase in promoting metastasis of solid tumors and in particular colorectal cancer at multiple stages, affecting tumor cell proliferation, invasion, and angiogenesis. This emerging research has stimulated significant interest in lysyl oxidase as a strong candidate for developing and deploying inhibitors as functional efficacious cancer therapeutics. In this review, we discuss the rapidly expanding body of knowledge concerning lysyl oxidase in solid tumor progression, highlighting recent advancements in the field of colorectal cancer.

  5. Postdiagnostic intake of one-carbon nutrients and alcohol in relation to colorectal cancer survival.

    Science.gov (United States)

    Lochhead, Paul; Nishihara, Reiko; Qian, Zhi Rong; Mima, Kosuke; Cao, Yin; Sukawa, Yasutaka; Kim, Sun A; Inamura, Kentaro; Zhang, Xuehong; Wu, Kana; Giovannucci, Edward; Meyerhardt, Jeffrey A; Chan, Andrew T; Fuchs, Charles S; Ogino, Shuji

    2015-11-01

    Observational data have suggested that intakes of nutrients involved in one-carbon metabolism are inversely associated with risk of colorectal carcinoma and adenomas. In contrast, results from some preclinical studies and cardiovascular and chemoprevention trials have raised concerns that high folate intake may promote carcinogenesis by facilitating the progression of established neoplasia. We tested the hypothesis that higher total folate intake (including food folate and folic acid from fortified foods and supplements) or other one-carbon nutrient intakes might be associated with poorer survival after a diagnosis of colorectal cancer. We used rectal and colon cancer cases within the following 2 US prospective cohort studies: the Nurses' Health Study and the Health Professionals Follow-Up Study. Biennial questionnaires were used to gather information on medical history and lifestyle factors, including smoking and alcohol consumption. B-vitamin and methionine intakes were derived from food-frequency questionnaires. Data on tumor molecular characteristics (including microsatellite instability, CpG island methylator phenotype, KRAS, BRAF, and PIK3CA mutations, and long interspersed nucleotide element 1 methylation level) were available for a subset of cases. We assessed colorectal cancer-specific mortality according to postdiagnostic intakes of one-carbon nutrients with the use of multivariable Cox proportional hazards regression models. In 1550 stage I-III colorectal cancer cases with a median follow-up of 14.9 y, we documented 641 deaths including 176 colorectal cancer-specific deaths. No statistically significant associations were observed between postdiagnostic intakes of folate or other one-carbon nutrients and colorectal cancer-specific mortality (multivariate P-trend ≥ 0.21). In an exploratory molecular pathologic epidemiology survival analysis, there was no significant interaction between one-carbon nutrients or alcohol and any of the tumor molecular

  6. Red and processed meat and colorectal cancer incidence: meta-analysis of prospective studies.

    Science.gov (United States)

    Chan, Doris S M; Lau, Rosa; Aune, Dagfinn; Vieira, Rui; Greenwood, Darren C; Kampman, Ellen; Norat, Teresa

    2011-01-01

    The evidence that red and processed meat influences colorectal carcinogenesis was judged convincing in the 2007 World Cancer Research Fund/American Institute of Cancer Research report. Since then, ten prospective studies have published new results. Here we update the evidence from prospective studies and explore whether there is a non-linear association of red and processed meats with colorectal cancer risk. Relevant prospective studies were identified in PubMed until March 2011. For each study, relative risks and 95% confidence intervals (CI) were extracted and pooled with a random-effects model, weighting for the inverse of the variance, in highest versus lowest intake comparison, and dose-response meta-analyses. Red and processed meats intake was associated with increased colorectal cancer risk. The summary relative risk (RR) of colorectal cancer for the highest versus the lowest intake was 1.22 (95% CI  =  1.11-1.34) and the RR for every 100 g/day increase was 1.14 (95% CI  =  1.04-1.24). Non-linear dose-response meta-analyses revealed that colorectal cancer risk increases approximately linearly with increasing intake of red and processed meats up to approximately 140 g/day, where the curve approaches its plateau. The associations were similar for colon and rectal cancer risk. When analyzed separately, colorectal cancer risk was related to intake of fresh red meat (RR(for 100 g/day increase)  =  1.17, 95% CI  =  1.05-1.31) and processed meat (RR (for 50 g/day increase)  =  1.18, 95% CI  =  1.10-1.28). Similar results were observed for colon cancer, but for rectal cancer, no significant associations were observed. High intake of red and processed meat is associated with significant increased risk of colorectal, colon and rectal cancers. The overall evidence of prospective studies supports limiting red and processed meat consumption as one of the dietary recommendations for the prevention of colorectal cancer.

  7. Red and processed meat and colorectal cancer incidence: meta-analysis of prospective studies.

    Directory of Open Access Journals (Sweden)

    Doris S M Chan

    Full Text Available BACKGROUND: The evidence that red and processed meat influences colorectal carcinogenesis was judged convincing in the 2007 World Cancer Research Fund/American Institute of Cancer Research report. Since then, ten prospective studies have published new results. Here we update the evidence from prospective studies and explore whether there is a non-linear association of red and processed meats with colorectal cancer risk. METHODS AND FINDINGS: Relevant prospective studies were identified in PubMed until March 2011. For each study, relative risks and 95% confidence intervals (CI were extracted and pooled with a random-effects model, weighting for the inverse of the variance, in highest versus lowest intake comparison, and dose-response meta-analyses. Red and processed meats intake was associated with increased colorectal cancer risk. The summary relative risk (RR of colorectal cancer for the highest versus the lowest intake was 1.22 (95% CI  =  1.11-1.34 and the RR for every 100 g/day increase was 1.14 (95% CI  =  1.04-1.24. Non-linear dose-response meta-analyses revealed that colorectal cancer risk increases approximately linearly with increasing intake of red and processed meats up to approximately 140 g/day, where the curve approaches its plateau. The associations were similar for colon and rectal cancer risk. When analyzed separately, colorectal cancer risk was related to intake of fresh red meat (RR(for 100 g/day increase  =  1.17, 95% CI  =  1.05-1.31 and processed meat (RR (for 50 g/day increase  =  1.18, 95% CI  =  1.10-1.28. Similar results were observed for colon cancer, but for rectal cancer, no significant associations were observed. CONCLUSIONS: High intake of red and processed meat is associated with significant increased risk of colorectal, colon and rectal cancers. The overall evidence of prospective studies supports limiting red and processed meat consumption as one of the dietary recommendations for the

  8. Postdiagnostic intake of one-carbon nutrients and alcohol in relation to colorectal cancer survival123

    Science.gov (United States)

    Lochhead, Paul; Nishihara, Reiko; Qian, Zhi Rong; Mima, Kosuke; Cao, Yin; Sukawa, Yasutaka; Kim, Sun A; Inamura, Kentaro; Zhang, Xuehong; Wu, Kana; Giovannucci, Edward; Meyerhardt, Jeffrey A; Chan, Andrew T; Fuchs, Charles S; Ogino, Shuji

    2015-01-01

    Background: Observational data have suggested that intakes of nutrients involved in one-carbon metabolism are inversely associated with risk of colorectal carcinoma and adenomas. In contrast, results from some preclinical studies and cardiovascular and chemoprevention trials have raised concerns that high folate intake may promote carcinogenesis by facilitating the progression of established neoplasia. Objective: We tested the hypothesis that higher total folate intake (including food folate and folic acid from fortified foods and supplements) or other one-carbon nutrient intakes might be associated with poorer survival after a diagnosis of colorectal cancer. Design: We used rectal and colon cancer cases within the following 2 US prospective cohort studies: the Nurses’ Health Study and the Health Professionals Follow-Up Study. Biennial questionnaires were used to gather information on medical history and lifestyle factors, including smoking and alcohol consumption. B-vitamin and methionine intakes were derived from food-frequency questionnaires. Data on tumor molecular characteristics (including microsatellite instability, CpG island methylator phenotype, KRAS, BRAF, and PIK3CA mutations, and long interspersed nucleotide element 1 methylation level) were available for a subset of cases. We assessed colorectal cancer–specific mortality according to postdiagnostic intakes of one-carbon nutrients with the use of multivariable Cox proportional hazards regression models. Results: In 1550 stage I–III colorectal cancer cases with a median follow-up of 14.9 y, we documented 641 deaths including 176 colorectal cancer–specific deaths. No statistically significant associations were observed between postdiagnostic intakes of folate or other one-carbon nutrients and colorectal cancer–specific mortality (multivariate P-trend ≥ 0.21). In an exploratory molecular pathologic epidemiology survival analysis, there was no significant interaction between one

  9. Brain metastases from colorectal cancer

    DEFF Research Database (Denmark)

    Vagn-Hansen, Chris Aksel; Rafaelsen, Søren Rafael

    2001-01-01

    Brain metastases from colorectal cancer are rare. The prognosis for patients with even a single resectable brain metastasis is poor. A case of surgically treated cerebral metastasis from a rectal carcinoma is reported. The brain tumour was radically resected. However, cerebral, as well...... as extracerebral, disease recurred 12 months after diagnosis. Surgical removal of colorectal metastatic brain lesions in selected cases results in a longer survival time....

  10. [Colorectal cancer prevention by flavonoids].

    Science.gov (United States)

    Hoensch, Harald; Richling, Elke; Kruis, Wolfgang; Kirch, Wilhelm

    2010-08-01

    Valid, sustained and safe clinical means of colorectal cancer prevention are still lacking, but they are urgently needed to lower the incidence of colorectal cancer. Dietary factors and phytochemicals such as flavonoids play an important role for prevention. A selective search of the literature using PubMed was performed with the following key words: flavonoids, cancer, therapy, colorectal cancer focused on clinical queries. Results of clinical studies including the authors' own were compared. In vivo and in vitro studies with animals, cell cultures and subcellular components provide ample evidence for antimutagenic and anticarcinogenic effects of flavonoids as shown for multiple biological and molecular endpoints. Isoflavonoids in vitro have been shown to induce proliferation of breast cancer cells. Epidemiologic trials (cohort, case-control and cross-sectional studies) yielded inconsistent results for flavonoid protection. Systematic reviews and meta-analyses support the protective role of tea flavonoids on adenoma incidence. An interventional pilot study with sustained flavonoid supplementation was shown to reduce the rate of neoplasia in patients with resected colorectal cancer. Selected flavonoids possess antimutagenic and anticarcinogenic properties and could reduce the incidence of colorectal neoplasias as shown in epidemiologic trials. Randomized controlled clinical studies with flavonoid intervention are necessary to provide evidence for their role in colorectal cancer prevention.

  11. Spontaneous initiation, promotion and progression of colorectal cancer in the novel A/J Min/+ mouse.

    Science.gov (United States)

    Sødring, Marianne; Gunnes, Gjermund; Paulsen, Jan Erik

    2016-04-15

    The C57BL/6J multiple intestinal neoplasia (Min/+) mouse is a widely used murine model for familial adenomatous polyposis, a hereditary form of human colorectal cancer. However, it is a questionable model partly because the vast majority of tumors arise in the small intestine, and partly because the fraction of tumors that progress to invasive carcinomas is minuscule. A/J mice are typically more susceptible to carcinogen-induced colorectal cancer than C57BL/6J mice. To investigate whether the novel Min/+ mouse on the A/J genetic background could be a better model for colorectal cancer, we examined the spontaneous intestinal tumorigenesis in 81 A/J Min/+ mice ranging in age from 4 to 60 weeks. The A/J Min/+ mouse exhibited a dramatic increase in number of colonic lesions when compared to what has been reported for the conventional Min/+ mouse; however, an increase in small intestinal lesions did not occur. In addition, this novel mouse model displayed a continual development of colonic lesions highlighted by the transition from early lesions (flat ACF) to tumors over time. In mice older than 40 weeks, 13 colonic (95% CI: 8.7-16.3) and 21 small intestinal (95% CI: 18.6-24.3) tumors were recorded. Notably, a considerable proportion of those lesions progressed to carcinomas in both the colon (21%) and small intestine (51%). These findings more closely reflect aspects of human colorectal carcinogenesis. In conclusion, the novel A/J Min/+ mouse may be a relevant model for initiation, promotion and progression of colorectal cancer. © 2015 UICC.

  12. Epigenomic diversity of colorectal cancer indicated by LINE-1 methylation in a database of 869 tumors

    Directory of Open Access Journals (Sweden)

    Schernhammer Eva S

    2010-05-01

    Full Text Available Abstract Background Genome-wide DNA hypomethylation plays a role in genomic instability and carcinogenesis. LINE-1 (L1 retrotransposon constitutes a substantial portion of the human genome, and LINE-1 methylation correlates with global DNA methylation status. LINE-1 hypomethylation in colon cancer has been strongly associated with poor prognosis. However, whether LINE-1 hypomethylators constitute a distinct cancer subtype remains uncertain. Recent evidence for concordant LINE-1 hypomethylation within synchronous colorectal cancer pairs suggests the presence of a non-stochastic mechanism influencing tumor LINE-1 methylation level. Thus, it is of particular interest to examine whether its wide variation can be attributed to clinical, pathologic or molecular features. Design Utilizing a database of 869 colorectal cancers in two prospective cohort studies, we constructed multivariate linear and logistic regression models for LINE-1 methylation (quantified by Pyrosequencing. Variables included age, sex, body mass index, family history of colorectal cancer, smoking status, tumor location, stage, grade, mucinous component, signet ring cells, tumor infiltrating lymphocytes, CpG island methylator phenotype (CIMP, microsatellite instability, expression of TP53 (p53, CDKN1A (p21, CTNNB1 (β-catenin, PTGS2 (cyclooxygenase-2, and FASN, and mutations in KRAS, BRAF, and PIK3CA. Results Tumoral LINE-1 methylation ranged from 23.1 to 90.3 of 0-100 scale (mean 61.4; median 62.3; standard deviation 9.6, and distributed approximately normally except for extreme hypomethylators [LINE-1 methylation Conclusions LINE-1 extreme hypomethylators appear to constitute a previously-unrecognized, distinct subtype of colorectal cancers, which needs to be confirmed by additional studies. Our tumor LINE-1 methylation data indicate enormous epigenomic diversity of individual colorectal cancers.

  13. Global histone modification of histone H3 in colorectal cancer and its precursor lesions.

    Science.gov (United States)

    Nakazawa, Tadao; Kondo, Tetsuo; Ma, Defu; Niu, Dongfeng; Mochizuki, Kunio; Kawasaki, Tomonori; Yamane, Tetsu; Iino, Hiroshi; Fujii, Hideki; Katoh, Ryohei

    2012-06-01

    Chromatin remodeling through histone modification is an important mechanism of epigenetic gene dysregulation in human cancers. However, little is known about global alteration of histone status during tumorigenesis and cancer progression. Histone H3 status was examined in benign and malignant colorectal tumors by immunohistochemistry and Western blotting. For immunohistochemical evaluation, 4 anti-histone H3 antibodies, specific to dimethylation at lysine 4 (H3K4me2), acetylation at lysine 9 (H3K9ac), dimethylation at lysine 9 (H3K9me2), and trimethylation at lysine 27 (H3K27me3), were used. On immunohistochemistry, H3K4me2, H3K9ac, and H3K27me3 showed no significant changes between normal and colorectal tumors. On the other hand, the global level of H3K9me2 was distinctly higher in neoplastic cells (adenoma and adenocarcinoma) than in normal glandular cells. In addition, it was significantly higher in adenocarcinoma than in adenoma. Correspondingly, Western blotting confirmed that H3K9me2 expression was significantly higher in adenocarcinomas than in normal colorectal mucosa. No alteration of H3K9me2 was observed with tumor differentiation and with the histological subtypes of colorectal cancers. These results suggest that aberration of the global H3K9me2 level is an important epigenetic event in colorectal tumorigenesis and carcinogenesis involved with gene regulation in neoplastic cells through chromatin remodeling. Copyright © 2012 Elsevier Inc. All rights reserved.

  14. Meat, vegetables and genetic polymorphisms and the risk of colorectal carcinomas and adenomas

    Directory of Open Access Journals (Sweden)

    Hansteen Inger-Lise

    2007-12-01

    Full Text Available Abstract Background The risk of sporadic colorectal cancer (CRC is mainly associated with lifestyle factors, particularly dietary factors. Diets high in red meat and fat and low in fruit and vegetables are associated with an increased risk of CRC. The dietary effects may be modulated by genetic polymorphisms in biotransformation genes. In this study we aimed to evaluate the role of dietary factors in combination with genetic factors in the different stages of colorectal carcinogenesis in a Norwegian population. Methods We used a case-control study design (234 carcinomas, 229 high-risk adenomas, 762 low-risk adenomas and 400 controls to test the association between dietary factors (meat versus fruit, berries and vegetables genetic polymorphisms in biotransformation genes (GSTM1, GSTT1, GSTP1 Ile105Val, EPHX1 Tyr113His and EPHX1 His139Arg, and risk of colorectal carcinomas and adenomas. Odds ratio (OR and 95% confidence interval (95% CI were estimated by binary logistic regression. Results A higher ratio of total meat to total fruit, berry and vegetable intake was positively associated with both high and low-risk adenomas, with approximately twice the higher risk in the 2nd quartile compared to the lowest quartile. For the high-risk adenomas this positive association was more obvious for the common allele (Tyr allele of the EPHX1 codon 113 polymorphism. An association was also observed for the EPHX1 codon 113 polymorphism in the low-risk adenomas, although not as obvious. Conclusion Although, the majority of the comparison groups are not significant, our results suggest an increased risk of colorectal adenomas in individuals for some of the higher ratios of total meat to total fruit, berry and vegetable intake. In addition the study supports the notion that the biotransformation enzymes GSTM1, GSTP1 and EPHX1 may modify the effect of dietary factors on the risk of developing colorectal carcinoma and adenoma.

  15. Robotics in Colorectal Surgery

    Science.gov (United States)

    Weaver, Allison; Steele, Scott

    2016-01-01

    Over the past few decades, robotic surgery has developed from a futuristic dream to a real, widely used technology. Today, robotic platforms are used for a range of procedures and have added a new facet to the development and implementation of minimally invasive surgeries. The potential advantages are enormous, but the current progress is impeded by high costs and limited technology. However, recent advances in haptic feedback systems and single-port surgical techniques demonstrate a clear role for robotics and are likely to improve surgical outcomes. Although robotic surgeries have become the gold standard for a number of procedures, the research in colorectal surgery is not definitive and more work needs to be done to prove its safety and efficacy to both surgeons and patients. PMID:27746895

  16. Epigenetics of colorectal cancer.

    Science.gov (United States)

    Goel, Ajay; Boland, C Richard

    2012-12-01

    In the early years of the molecular biology revolution, cancer research was mainly focused on genetic changes (ie, those that altered DNA sequences). Although this has been extremely useful as our understanding of the pathogenesis and biology of cancer has grown and matured, there is another realm in tumor development that does not involve changing the sequence of cellular DNA. This field is called "epigenetics" and broadly encompasses changes in the methylation of cytosines in DNA, changes in histone and chromatin structure, and alterations in the expression of microRNAs, which control the stability of many messenger RNAs and serve as "master regulators" of gene expression. This review focuses on the epigenetics of colorectal cancer and illustrates the impact epigenetics has had on this field. Copyright © 2012 AGA Institute. Published by Elsevier Inc. All rights reserved.

  17. Association between red meat consumption and colon cancer: A systematic review of experimental results.

    Science.gov (United States)

    Turner, Nancy D; Lloyd, Shannon K

    2017-04-01

    A role for red and processed meat in the development of colorectal cancer has been proposed based largely on evidence from observational studies in humans, especially in those populations consuming a westernized diet. Determination of causation specifically by red or processed meat is contingent upon identification of plausible mechanisms that lead to colorectal cancer. We conducted a systematic review of the available evidence to determine the availability of plausible mechanistic data linking red and processed meat consumption to colorectal cancer risk. Forty studies using animal models or cell cultures met specified inclusion criteria, most of which were designed to examine the role of heme iron or heterocyclic amines in relation to colon carcinogenesis. Most studies used levels of meat or meat components well in excess of those found in human diets. Although many of the experiments used semi-purified diets designed to mimic the nutrient loads in current westernized diets, most did not include potential biologically active protective compounds present in whole foods. Because of these limitations in the existing literature, there is currently insufficient evidence to confirm a mechanistic link between the intake of red meat as part of a healthy dietary pattern and colorectal cancer risk. Impact statement Current recommendations to reduce colon cancer include the reduction or elimination of red or processed meats. These recommendations are based on data from epidemiological studies conducted among cultures where meat consumption is elevated and consumption of fruits, vegetables, and whole grains are reduced. This review evaluated experimental data exploring the putative mechanisms whereby red or processed meats may contribute to colon cancer. Most studies used levels of meat or meat-derived compounds that were in excess of those in human diets, even in cultures where meat intake is elevated. Experiments where protective dietary compounds were used to mitigate the

  18. The multidrug resistance 1 (MDR1 gene polymorphism G-rs3789243-A is not associated with disease susceptibility in Norwegian patients with colorectal adenoma and colorectal cancer; a case control study

    Directory of Open Access Journals (Sweden)

    Hamfjord Julian

    2009-02-01

    Full Text Available Abstract Background Smoking, dietary factors, and alcohol consumption are known life style factors contributing to gastrointestinal carcinogenesis. Genetic variations in carcinogen handling may affect cancer risk. The multidrug resistance 1(MDR1/ABCB1 gene encodes the transport protein P-glycoprotein (a phase III xenobiotic transporter. P-glycoprotein is present in the intestinal mucosal lining and restricts absorption of certain carcinogens, among these polycyclic aromatic hydrocarbons. Moreover, P-glycoprotein transports various endogenous substrates such as cytokines and chemokines involved in inflammation, and may thereby affect the risk of malignity. Hence, genetic variations that modify the function of P-glycoprotein may be associated with the risk of colorectal cancer (CRC. We have previously found an association between the MDR1 intron 3 G-rs3789243-A polymorphism and the risk of CRC in a Danish study population. The aim of this study was to investigate if this MDR1 polymorphism was associated with risk of colorectal adenoma (CA and CRC in the Norwegian population. Methods Using a case-control design, the association between the MDR1 intron 3 G-rs3789243-A polymorphism and the risk of colorectal carcinomas and adenomas in the Norwegian population was assessed in 167 carcinomas, 990 adenomas, and 400 controls. Genotypes were determined by allelic discrimination. Odds ratio (OR and 95 confidence interval (95% CI were estimated by binary logistic regression. Results No association was found between the MDR1 polymorphism (G-rs3789243-A and colorectal adenomas or cancer. Carriers of the variant allele of MDR1 intron 3 had odds ratios (95% CI of 0.97 (0.72–1.29 for developing adenomas, and 0.70 (0.41–1.21 for colorectal cancer, respectively, compared to homozygous wild type carriers. Conclusion The MDR1 intron 3 (G-rs3789243-A polymorphism was not associated with a risk of colorectal adenomas or carcinomas in the present Norwegian study

  19. [HNPCC (hereditary non-polyposis colorectal cancer) or Lynch syndrome: a syndrome related to a failure of DNA repair system].

    Science.gov (United States)

    Manceau, Gilles; Karoui, Mehdi; Charachon, Antoine; Delchier, Jean-Charles; Sobhani, Iradj

    2011-03-01

    The HNPCC syndrome (hereditary non polyposis colon cancer) or Lynch syndrome stands for an autosomic dominant condition leading to the most prevalent hereditary colo-rectal cancers (CCR). MMR (mismatch repair)'s genes are involved in carcinogenesis as they play a role in ADNA mismatch repair. Microsatellite instability (MSI+ phenotype) induced by germline mutations is characteristic of such tumors and is necessary to assert the diagnosis. The HNPCC syndrome is associated with a significant increased risk of CCR altogether with endometrium, upper urinary tract and small bowel carcinomas as well as ovarian, biliary system and gastric cancers although of lesser extent. It is of importance to diagnose HNPCC syndrome prior to the treatment starts because it may influence patient's (as well as her/his relatives) disease management (type of surgery, surveillance and screening exams). New French recommendations, developed in 2009, about prophylactic colo-rectal and gynecologic surgeries and monitoring update latest ones published on 2004.

  20. Cyclooxygenase as a target for chemoprevention in colorectal cancer: lost cause or a concept coming of age?

    LENUS (Irish Health Repository)

    Doherty, Glen A

    2009-02-01

    COX-2 is upregulated at an early stage in colorectal carcinogenesis and generates prostaglandins, which promote cancer cell proliferation, impair apoptosis and enhance angiogenesis, promoting tumour growth and metastasis. There are ample data from animal models and human studies to demonstrate enhanced tumour progression associated with COX-2 activity in cancer cells. Conversely, NSAIDs including aspirin inhibit COX-2 and, therefore, have anti-neoplastic properties. There has been sustained interest in COX-2 as a chemopreventive target in colorectal cancer (CRC) and although both aspirin and COX-2 selective NSAIDs have demonstrated efficacy, adverse effects have limited their widespread adoption. In particular, evidence of the cardiovascular effects of COX-2 selective inhibitors has led to questioning of the suitability of COX-2 as a target for chemoprevention. This review examines the basis for targeting COX-2 in CRC chemoprevention, evaluates the efficacy and safety of the approach and examines future strategies in this area.

  1. Colorectal Cancer: The Importance of Early Detection

    Science.gov (United States)

    ... of this page please turn JavaScript on. Feature: Colorectal Cancer The Importance of Early Detection Past Issues / Summer ... Cancer of the colon or rectum is called colorectal cancer. The colon and the rectum are part of ...

  2. Molecular genetics of colorectal cancer Genética molecular del cáncer colorrectal

    Directory of Open Access Journals (Sweden)

    D. Cruz-Bustillo Clarens

    2004-01-01

    Full Text Available Colorectal tumours constitute an excellent system to study carcinogenesis and the molecular events implicated in the development of cancer. Attending to the way it is transmitted, colorectal cancer may appear in one of three forms: sporadic, familial, and hereditary. The sporadic form is most common and has no familial or hereditary associated factor thus far, while familial and hereditary forms show the same inheritance pattern. Hereditary colorectal cancers develop by means of defined stages that go from lesions in the crypt of the colon through adenomas to manifest cancer. They are characterised by the accumulation of multiple mutations in tumour suppressor genes and oncogenes that affect the balance between cell proliferation and apoptosis. The colorectal carcinogenesis pathway is not unique and there are probably several ways for the initiation, development and progression of colorectal tumours.Los tumores colorrectales constituyen un excelente sistema para estudiar la carcinogénesis y los eventos moleculares involucrados en el desarrollo de un tumor. El cáncer colorrectal puede presentarse en tres formas, según su forma de transmisión: esporádico, familiar y hereditario. La forma esporádica que es la mayoritaria, no tiene hasta el momento ningún factor familiar o hereditario asociado, mientras que las formas familiares y hereditarias siguen un patrón de herencia en la propensión familiar a padecerlo. Los cánceres colorrectales hereditarios se desarrollan mediante etapas definidas que van desde lesiones en la cripta del colon a través de adenomas hasta manifestar el cáncer y se caracterizan por la acumulación de múltiples mutaciones en genes supresores de tumor y oncogenes que afectan el balance entre la proliferación celular y la apoptosis. La vía de carcinogénesis colorrectal no es una sola y probablemente existan varios caminos para el inicio, desarrollo y progresión de un tumor colorrectal.

  3. The Association Between Molecular Markers in Colorectal Sessile Serrated Polyps and Colorectal Cancer Risk

    Science.gov (United States)

    2017-08-01

    AWARD NUMBER: W81XWH-15-1-0273 TITLE: The Association between Molecular Markers in Colorectal Sessile Serrated Polyps and Colorectal Cancer ...Colorectal Cancer Risk 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-15-1-0273 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Andrea Burnett-Hartman 5d... cancer in patients with sessile serrated colorectal polyps (SSPs). The project’s specific aims are as follows: 1) Estimate the risk of colorectal

  4. The TP53 tumour suppressor gene in colorectal carcinomas. I. Genetic alterations on chromosome 17.

    Science.gov (United States)

    Meling, G. I.; Lothe, R. A.; Børresen, A. L.; Graue, C.; Hauge, S.; Clausen, O. P.; Rognum, T. O.

    1993-01-01

    In 231 colorectal carcinomas, allele variation at four restriction fragments length polymorphisms (RFLP) loci on chromosome 17 have been studied by Southern analysis. Heterozygous loss of the TP53 gene was found in 68% (129/189) of the carcinomas informative on both chromosome arms. In 41% (77/189) of the carcinomas the loss was found only on 17p. Two probes were used to detect alterations on 17p, pBHP53 and pYNZ22. When loss was demonstrated with pYNZ22, pBHP53 also always showed loss (n = 45), whereas when loss was demonstrated with pBHP53, only 45 of 54 (83%) showed loss with pYNZ22. Loss on 17q was found in 34% (64/189) of the carcinomas, and 6% (12/189) had loss on this chromosome arm, only. Loss on 17q was significantly associated with loss on 17p (P < 0.01). These data confirm that the TP53 gene is the target of loss on chromosome arm 17p in colorectal carcinomas, and demonstrate that loss of the TP53 gene is most frequently part of limited, subchromosomal loss. Furthermore, the results do not suggest any additional tumour suppressor gene(s) on chromosome 17 involved in colorectal carcinogenesis. Images Figure 2 PMID:8094008

  5. Immunohistochemical Expression of Dual-Specificity Protein Phosphatase 4 in Patients with Colorectal Adenocarcinoma

    Directory of Open Access Journals (Sweden)

    Jongmin Sim

    2015-01-01

    Full Text Available The role of dual-specificity protein phosphatase 4 (DUSP4 appears to vary with the type of malignant tumors and is still controversial. The purpose of our study was to clarify the exact role of DUSP4 expression in colorectal adenocarcinoma. We constructed tissue microarrays and investigated DUSP4 expression by immunohistochemistry. DUSP4 was more frequently expressed in adenocarcinomas and lymph node/distant metastases compared to that in normal colorectal tissues and tubular adenomas (P<0.001. Mean DUSP4 expression score was significantly higher in malignant tumors than in benign lesions (P<0.001. DUSP4 expression was significantly correlated with older age (P=0.017, male gender (P=0.036, larger tumor size (P=0.014, nonmucinous tumor type (P=0.023, and higher T stage (P=0.040. Kaplan-Meier survival curves revealed a significant effect of DUSP4 expression on both overall survival and disease-free survival in AJCC stage I (P=0.008 and P=0.003, resp., log-rank test and male gender (P=0.017 and P=0.049, resp., log-rank test. DUSP4 protein is frequently upregulated in colorectal adenocarcinoma and may play an important role in carcinogenesis and cancer progression and may be a marker of adverse prognosis.

  6. Analysis of Candidate Genes in Occurrence and Growth of Colorectal Adenomas

    Directory of Open Access Journals (Sweden)

    Sylviane Olschwang

    2009-01-01

    Full Text Available Predisposition to sporadic colorectal tumours is influenced by genes with minor phenotypic effects. A case-control study was set up on 295 patients treated for a large adenoma matched with polyp-free individuals on gender, age, and geographic origin in a 1 : 2 proportion. A second group of 302 patients treated for a small adenoma was also characterized to distinguish effects on adenoma occurrence and growth. We focussed the study on 38 single nucleotide polymorphisms (SNPs encompassing 14 genes involved in colorectal carcinogenesis. Effect of SNPs was tested using unconditional logistic regression. Comparisons were made for haplotypes within a given gene and for biologically relevant genes combinations using the combination test. The APC p.Glu1317Gly variant appeared to influence the adenoma growth (P=.04, exact test but not its occurrence. This result needs to be replicated and genome-wide association studies may be necessary to fully identify low-penetrance alleles involved in early stages of colorectal tumorigenesis.

  7. E-cadherin and β-catenin expression in canine colorectal adenocarcinoma.

    Science.gov (United States)

    Aresu, L; Pregel, P; Zanetti, R; Caliari, D; Biolatti, B; Castagnaro, M

    2010-12-01

    E-cadherin and its associated cytoplasmic proteins, including β-catenin, have been examined as potential oncogenic markers due to the significant correlation between tumour dedifferentiation and the invasive capacity of epithelial tumours. The purpose of this study was to evaluate the expression of E-cadherin and β-catenin in canine colorectal cancer using immunohistochemistry and to examine the relationship between this expression and various clinicopathological variables. The expression pattern of E-cadherin and β-catenin was investigated in 44 colorectal canine carcinomas. In the intestinal mucosa of noncancerous areas, epithelial cells demonstrated equally strong membranous expression of E-cadherin and β-catenin localised to the cell-cell junctions. Reduced expression of E-cadherin and β-catenin was demonstrated in 75% and 81.8% of the colorectal carcinoma cases, respectively. The down-regulation of both E-cadherin and β-catenin was correlated with decreased differentiation and increased tumour grade. In addition, the expression of β-catenin was correlated with tumour size. These results suggest that dysfunction of the E-cadherin-catenin complex starts in the early stages of carcinogenesis and that the disruption of the tissue architecture is progressively associated with the invasion of the tumour. Copyright © 2010 Elsevier Ltd. All rights reserved.

  8. Elevated plasma gastrin, CEA, and CA 19-9 levels decrease after colorectal cancer resection.

    Science.gov (United States)

    Bombski, G; Gasiorowska, A; Orszulak-Michalak, D; Neneman, B; Kotynia, J; Strzelczyk, J; Janiak, A; Malecka-Panas, E

    2003-03-01

    Gastrin stimulates mucosal growth of much of the gastrointestinal tract and has also been implicated in promoting growth of colonic tumors, but its role in colorectal carcinogenesis remains controversial. This study determined fasting serum gastrin levels before and after surgery for colorectal cancer (CRC) and the relationship to the clinical stage of the disease to investigate it possible prognostic role. Fasting radioimmunoassay gastrin, CA 19-9, and CEA levels were measured before and after surgery for CRC. Helicobacter pylori status was also assessed since it causes significant hypergastrinemia. Mean fasting plasma gastrin level was significantly higher in CRC patients than in controls before surgery but not 59 days after surgery. Mean CEA and CA 19-9 levels were significantly higher in patients with CRC before surgery than after tumor resection. There was a significant positive correlation between the plasma gastrin, CEA, and CA 19-9 levels and the CRC stage (Dukes' classification). The significance of gastrin as a marker for diagnosis or prognostic purposes in colorectal cancer needs to be further examined.

  9. Expression profiling of colorectal cancer cells reveals inhibition of DNA replication licensing by extracellular calcium.

    Science.gov (United States)

    Aggarwal, Abhishek; Schulz, Herbert; Manhardt, Teresa; Bilban, Martin; Thakker, Rajesh V; Kallay, Enikö

    2017-06-01

    Colorectal cancer is one of the most common cancers in industrialised societies. Epidemiological studies, animal experiments, and randomized clinical trials have shown that dietary factors can influence all stages of colorectal carcinogenesis, from initiation through promotion to progression. Calcium is one of the factors with a chemoprophylactic effect in colorectal cancer. The aim of this study was to understand the molecular mechanisms of the anti-tumorigenic effects of extracellular calcium ([Ca(2+)]o) in colon cancer cells. Gene expression microarray analysis of colon cancer cells treated for 1, 4, and 24h with 2mM [Ca(2+)]o identified significant changes in expression of 1571 probe sets (ANOVA, pcalcium-sensing receptor (CaSR), a G protein-coupled receptor is a mediator involved in this process. To test whether these results were physiologically relevant, we fed mice with a standard diet containing low (0.04%), intermediate (0.1%), or high (0.9%) levels of dietary calcium. The main molecules regulating replication licensing were inhibited also in vivo, in the colon of mice fed high calcium diet. We show that among the mechanisms behind the chemopreventive effect of [Ca(2+)]o is inhibition of replication licensing, a process often deregulated in neoplastic transformation. Our data suggest that dietary calcium is effective in preventing replicative stress, one of the main drivers of cancer and this process is mediated by the calcium-sensing receptor. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  10. Genetic Testing for Hereditary Colorectal Cancer

    Science.gov (United States)

    ... Facebook Tweet Share Compartir Having a family health history of colorectal (colon) cancer can make you more likely to get colorectal ... Health History? If you have a family health history of colorectal cancer, your doctor may consider your family health history ...

  11. Cost-effectiveness of colorectal cancer screening

    NARCIS (Netherlands)

    I. Lansdorp-Vogelaar (Iris); A.B. Knudsen (Amy); H. Brenner (Hermann)

    2011-01-01

    textabstractColorectal cancer is an important public health problem. Several screening methods have been shown to be effective in reducing colorectal cancer mortality. The objective of this review was to assess the cost-effectiveness of the different colorectal cancer screening methods and to

  12. Oral microbiome and history of smoking and colorectal cancer.

    Science.gov (United States)

    Kato, Ikuko; Vasquez, Adrian A; Moyerbrailean, Gregory; Land, Susan; Sun, Jun; Lin, Ho-Sheng; Ram, Jeffrey L

    2016-10-01

    The equilibrium of oral microbiome may be altered by environmental factors, including cigarette smoking. Several recent studies also suggest that oral pathogens causing periodontal disease, such as Fusobacterium nucleatum, are involved in pathogenesis of colorectal cancer. For this study oral rinse DNA samples from 190 participants in a population-based case-control study for colorectal cancer were used to amplify a V3-V4 region of bacterial 16S rRNA gene. The amplicons were sequenced using Illumina MiSeq paired end chemistry on two runs, yielding approximately 35 million filtered reads which were assigned to bacterial phyla. No association was found between Fusobacterium abundance or presence and colorectal cancer. However, adjusted for age and experimental batch, colorectal cancer history was associated with increased presence of genus Lactobacillus and increased relative abundance of Rothia by 28% and current smoking was associated with a 33% decrease in relative counts of Betaproteobacteria (primarily Neisseria) and 23% increase in relative abundance of Veillonellaceae family. We also found that smoking had significant effects on the 2nd component scores and 2nd coordinate distances in principal component and coordinate analyses. It remains to be elucidated whether the observed differences can be translated into biochemical changes in oral environment, thus potentially affecting oral health.

  13. A Gene Expression Classifier of Node-Positive Colorectal Cancer

    Directory of Open Access Journals (Sweden)

    Paul F. Meeh

    2009-10-01

    Full Text Available We used digital long serial analysis of gene expression to discover gene expression differences between node-negative and node-positive colorectal tumors and developed a multigene classifier able to discriminate between these two tumor types. We prepared and sequenced long serial analysis of gene expression libraries from one node-negative and one node-positive colorectal tumor, sequenced to a depth of 26,060 unique tags, and identified 262 tags significantly differentially expressed between these two tumors (P < 2 x 10-6. We confirmed the tag-to-gene assignments and differential expression of 31 genes by quantitative real-time polymerase chain reaction, 12 of which were elevated in the node-positive tumor. We analyzed the expression levels of these 12 upregulated genes in a validation panel of 23 additional tumors and developed an optimized seven-gene logistic regression classifier. The classifier discriminated between node-negative and node-positive tumors with 86% sensitivity and 80% specificity. Receiver operating characteristic analysis of the classifier revealed an area under the curve of 0.86. Experimental manipulation of the function of one classification gene, Fibronectin, caused profound effects on invasion and migration of colorectal cancer cells in vitro. These results suggest that the development of node-positive colorectal cancer occurs in part through elevated epithelial FN1 expression and suggest novel strategies for the diagnosis and treatment of advanced disease.

  14. Genetic alterations within the retinoblastoma locus in colorectal carcinomas. Relation to DNA ploidy pattern studied by flow cytometric analysis.

    Science.gov (United States)

    Meling, G. I.; Lothe, R. A.; Børresen, A. L.; Hauge, S.; Graue, C.; Clausen, O. P.; Rognum, T. O.

    1991-01-01

    Alterations within the retinoblastoma (Rb) gene, as detected by the VNTR probe p68RS2.0, and flow cytometric DNA pattern have been analysed in 255 colorectal carcinomas. A total of 35.3% of the tumours had alterations within the Rb gene. Amplification of one allele was demonstrated in 29.5% of the tumours, and loss of heterozygosity was found in 11.5%. No association was found between amplification within the Rb gene and clinicopathological characteristics of the patients. The high frequency of alterations demonstrated within the Rb gene, suggests that this gene is involved in colorectal carcinogenesis with amplification as by far the most abundant genetic alteration. This may imply that the Rb gene has an oncogene-like function in colorectal carcinomas, rather than acting as a tumour suppressor gene. Sixty-three per cent of the carcinomas were DNA aneuploid, and a significant association was demonstrated between amplification within the Rb gene and DNA aneuploidy (P less than 0.01). Two other chromosome loci were analysed, on chromosome 1p (probe pYNZ2) and on chromosome 2p (probe pYNH24), respectively. On chromosome 1p, heterozygous loss was found in 22.2% of the tumours, indicating an involvement of this chromosome in a subset of colorectal carcinomas. Images Figure 1 PMID:1911187

  15. Magnesium intake, plasma C-peptide, and colorectal cancer incidence in US women: a 28-year follow-up study

    Science.gov (United States)

    Zhang, X; Giovannucci, E L; Wu, K; Smith-Warner, S A; Fuchs, C S; Pollak, M; Willett, W C; Ma, J

    2012-01-01

    Background: Laboratory studies suggest a possible role of magnesium intake in colorectal carcinogenesis but epidemiological evidence is inconclusive. Method: We tested magnesium–colorectal cancer hypothesis in the Nurses' Health Study, in which 85 924 women free of cancer in 1980 were followed until June 2008. Cox proportional hazards regression models were used to estimate multivariable relative risks (MV RRs, 95% confidence intervals). Results: In the age-adjusted model, magnesium intake was significantly inversely associated with colorectal cancer risk; the RRs from lowest to highest decile of total magnesium intake were 1.0 (ref), 0.93, 0.81, 0.72, 0.74, 0.77, 0.72, 0.75, 0.80, and 0.67 (Ptrendmagnesium intakes were significantly inversely associated with concentrations of plasma C-peptide in age-adjusted model (Ptrend=0.002) but not in multivariate-adjusted model (Ptrend=0.61). Results did not differ by subsite or modified by calcium intakes or body mass index. Conclusion: These prospective results do not support an independent association of magnesium intake with either colorectal cancer risk or plasma C-peptide levels in women. PMID:22415230

  16. Effect of DNA methylation profile on OATP3A1 and OATP4A1 transcript levels in colorectal cancer.

    Science.gov (United States)

    Rawłuszko-Wieczorek, Agnieszka Anna; Horst, Nikodem; Horbacka, Karolina; Bandura, Artur Szymon; Świderska, Monika; Krokowicz, Piotr; Jagodziński, Paweł Piotr

    2015-08-01

    Epidemiological studies indicate that 17β-estradiol (E2) prevents colorectal cancer (CRC). Organic anion transporting polypeptides (OATPs) are involved in the cellular uptake of various endogenous and exogenous substrates, including hormone conjugates. Because transfer of estrone sulfate (E1-S) can contribute to intra-tissue conversion of estrone to the biologically active form -E2, it is evident that the expression patterns of OATPs may be relevant to the analysis of CRC incidence and therapy. We therefore evaluated DNA methylation and transcript levels of two members of the OATP family, OATP3A1 and OATP4A1, that may be involved in E1-S transport in colorectal cancer patients. We detected a significant reduction in OATP3A1 and a significant increase in OATP4A1 mRNA levels in cancerous tissue, compared with histopathologically unchanged tissue (n=103). Moreover, we observed DNA hypermethylation in the OATP3A1 promoter region in a small subset of CRC patients and in HCT116 and Caco-2 colorectal cancer cell lines. We also observed increased OATP3A1 transcript following treatment with 5-aza-2-deoxycytidine and sodium butyrate. The OATP4A1 promoter region was hypomethylated in analyzed tissues and CRC cell lines and was not affected by these treatments. Our results suggest a potential mechanism for OATP3A1 downregulation that involves DNA methylation during colorectal carcinogenesis. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  17. Telomerase abrogation dramatically accelerates TRF2-induced epithelial carcinogenesis

    OpenAIRE

    Blanco, Raquel; Muñoz, Purificación; Flores, Juana M.; Klatt, Peter; Blasco, María A.

    2007-01-01

    TRF2 is a telomere-binding protein with roles in telomere protection and telomere-length regulation. The fact that TRF2 is up-regulated in some human tumors suggests a role of TRF2 in cancer. Mice that overexpress TRF2 in the skin, K5TRF2 mice, show critically short telomeres and are susceptible to UV-induced carcinogenesis as a result of deregulated XPF/ERCC1 activity, a nuclease involved in UV damage repair. Here we demonstrate that, when in combination with telomerase deficiency, TRF2 acts...

  18. Bacterial infection increases risk of carcinogenesis by targeting mitochondria

    DEFF Research Database (Denmark)

    Strickertsson, Jesper A.B.; Desler, Claus; Rasmussen, Lene Juel

    2017-01-01

    pathways, and compares the impact of the bacterial alteration of mitochondrial function to that of cancer. Bacterial virulence factors have been demonstrated to induce mutations of mitochondrial DNA (mtDNA) and to modulate DNA repair pathways of the mitochondria. Furthermore, virulence factors can induce...... or impair the intrinsic apoptotic pathway. The effect of bacterial targeting of mitochondria is analogous to behavior of mitochondria in a wide array of tumours, and this strongly suggests that mitochondrial targeting of bacteria is a risk factor for carcinogenesis....

  19. Lysyl Oxidase Gene G473A Polymorphism and Cigarette Smoking in Association with a High Risk of Lung and Colorectal Cancers in a North Chinese Population.

    Science.gov (United States)

    Wang, Guoli; Shen, Yanqing; Cheng, Guang; Bo, Haimei; Lin, Jia; Zheng, Maogen; Li, Jianmin; Zhao, Yinzhi; Li, Wande

    2016-06-28

    The relationship among the lysyl oxidase (LOX) G473A single nucleotide polymorphism (SNP), cigarette smoking and lung, colorectal, colon and rectum cancer susceptibility was studied in 200 cases of lung cancer, 335 cases of colorectal cancer including 130 cases of colon cancer and 205 cases of rectum cancer, and 335 healthy people in Tangshan, China. Peripheral blood DNA samples were collected, DNA sequencing and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) performed, followed by multivariate logistic regression analysis. In comparison to LOX473GG genotype carriers, individuals with LOX473AA exhibited a higher susceptibility to lung, colon-rectum, colon, and rectum cancers with OR values amounting to 3.84-, 2.74-, 2.75-, and 2.74-fold of the control, respectively. In the LOX 473AA-positive population, females were more susceptible than males to carcinogenesis with OR values (female vs. male): 5.25 vs. 3.23, 2.29 vs. 1.51, 2.27 vs. 1.45, and 2.25 vs. 1.53, respectively, for lung, colon-rectum combined, colon, and rectum cancers. LOX G473A polymorphism apparently elevated human sensitivity to cigarette smoking carcinogens for eliciting cancers in the lung and colon only. Thus, LOX G473A polymorphism positively correlates with carcinogenesis and it may be used as an ideal intrinsic biomarker for prediction or diagnosis of carcinogenesis in humans.

  20. Lysyl Oxidase Gene G473A Polymorphism and Cigarette Smoking in Association with a High Risk of Lung and Colorectal Cancers in a North Chinese Population

    Directory of Open Access Journals (Sweden)

    Guoli Wang

    2016-06-01

    Full Text Available The relationship among the lysyl oxidase (LOX G473A single nucleotide polymorphism (SNP, cigarette smoking and lung, colorectal, colon and rectum cancer susceptibility was studied in 200 cases of lung cancer, 335 cases of colorectal cancer including 130 cases of colon cancer and 205 cases of rectum cancer, and 335 healthy people in Tangshan, China. Peripheral blood DNA samples were collected, DNA sequencing and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP performed, followed by multivariate logistic regression analysis. In comparison to LOX473GG genotype carriers, individuals with LOX473AA exhibited a higher susceptibility to lung, colon-rectum, colon, and rectum cancers with OR values amounting to 3.84-, 2.74-, 2.75-, and 2.74-fold of the control, respectively. In the LOX 473AA-positive population, females were more susceptible than males to carcinogenesis with OR values (female vs. male: 5.25 vs. 3.23, 2.29 vs. 1.51, 2.27 vs. 1.45, and 2.25 vs. 1.53, respectively, for lung, colon-rectum combined, colon, and rectum cancers. LOX G473A polymorphism apparently elevated human sensitivity to cigarette smoking carcinogens for eliciting cancers in the lung and colon only. Thus, LOX G473A polymorphism positively correlates with carcinogenesis and it may be used as an ideal intrinsic biomarker for prediction or diagnosis of carcinogenesis in humans.

  1. Dietary Carbohydrate, Glycemic Index, and Glycemic Load in Relation to Colorectal Cancer Risk in the Women’s Health Initiative

    Science.gov (United States)

    Kabat, Geoffrey C.; Shikany, James M.; Beresford, Shirley A. A.; Caan, Bette; Neuhouser, Marian L.; Tinker, Lesley F.; Rohan, Thomas E.

    2013-01-01

    Evidence implicating hyperinsulinemia and insulin resistance in the etiology of colorectal cancer suggests that a diet characterized by a high glycemic index and load may increase the risk of this disease, but previous studies have yielded inconsistent results. We assessed the association between intake of total carbohydrates, sugars, fiber, and the glycemic index (GI) and glycemic load (GL) of individual diets, and risk of developing colorectal cancer among 158,800 participants in the Women’s Health Initiative (WHI). We used a GI/GL database developed specifically for the WHI food-frequency questionnaire. Over an average of 7.8 years of follow-up, 1,476 incident cases of colorectal cancer were identified. Cox proportional hazards models were used to estimate the association between dietary factors classified by quintiles and risk of colorectal cancer, with adjustment for covariates. Total carbohydrate intake, glycemic index, glycemic load, and intake of sugars and fiber showed no association with colorectal cancer. Analyses by cancer subsite yielded null results, with the exception of a borderline positive association between glycemic load and rectal cancer (HR for the highest vs. lowest quintile 1.84, 95% confidence interval 0.95–3.56, p for trend 0.05). Analyses stratified by tertiles of body mass index and physical activity showed no evidence of effect modification by these factors. Results of this large study do not support of a role of a diet characterized by a high glycemic index or load in colorectal carcinogenesis in postmenopausal women. PMID:18618276

  2. Expression of core clock genes in colorectal tumour cells compared with normal mucosa

    DEFF Research Database (Denmark)

    Fonnes, S; Donatsky, A M; Gögenur, I

    2015-01-01

    AIM: Experimental studies have shown that some circadian core clock genes may act as tumour suppressors and have an important role in the response to oncological treatment. This study investigated the evidence regarding modified expression of core clock genes in colorectal cancer and its...... expression of colorectal cancer cells compared with healthy mucosa cells from specimens analysed by real-time or quantitative real-time polymer chain reaction. The expression of the core clock genes Period, Cryptochrome, Bmal1 and Clock in colorectal tumours were compared with healthy mucosa and correlated...... with clinicopathological features and survival. RESULTS: Seventy-four articles were identified and 11 studies were included. Overall, gene expression of Period was significantly decreased in colorectal cancer cells compared with healthy mucosa cells. This tendency was also seen in the gene expression of Clock. Other core...

  3. Polyyne-Enriched Extract from Oplopanax elatus Significantly Ameliorates the Progression of Colon Carcinogenesis in ApcMin/+ Mice

    Directory of Open Access Journals (Sweden)

    Xin Qiao

    2017-09-01

    Full Text Available Colorectal cancer (CRC is the third most common cancer in the world. Oplopanax elatus is widely used in traditional medicine. However, little is known about its pharmacological effects and bioactive compounds. We evaluated the effects of the polyyne-enriched extract from O. elatus (PEO on the progression of colon carcinogenesis in ApcMin/+ mice. In addition, these effects were also investigated in HCT116 and SW480 cells. After PEO oral administration (0.2% diet for 12 weeks, PEO significantly improved body weight changes and reduced the tumor burden and tumor multiplicity compared with the untreated mice. Meanwhile, western blot and immunohistochemistry results showed PEO significantly reduced the expression of β-catenin and cyclinD1 in both small intestine and the colon tissues compared with the untreated mice. In addition, PEO treatment significant decreased the cell viability in both HCT116 and SW480 cell lines. It also decreased the levels of β-catenin, cyclinD1, c-myc and p-GSK-3β in HCT116 and SW480 cells at 25 μM. These results indicate that PEO may have potential value in prevention of colon cancer by down-regulating Wnt-related protein.

  4. Hemidesmosome integrity protects the colon against colitis and colorectal cancer

    OpenAIRE

    Hamade, Hussein; Alpy, Fabien; Normand, Sylvain; Bruyere, Emilie; Lefebvre, Olivier; Mechine-Neuville, Agnes; Siebert, Stefanie; Pfister, Véronique; Lepage, Patricia; Laquerriere, Patrice; Dembele, Doulaye; Delanoye-Crespin, Anne; Rodius, Sophie; Robine, Sylvie; Kedinger, Michele

    2017-01-01

    Objective Epidemiological and clinical data indicate that patients suffering from IBD with long-standing colitis display a higher risk to develop colorectal high-grade dysplasia. Whereas carcinoma invasion and metastasis rely on basement membrane (BM) disruption, experimental evidence is lacking regarding the potential contribution of epithelial cell/BM anchorage on inflammation onset and subsequent neoplastic transformation of inflammatory lesions. Herein, we analyse the role of the alpha 6 ...

  5. Multifaceted nature of membrane microdomains in colorectal cancer

    OpenAIRE

    Jahn, Kristina A; Su, Yingying; Braet, Filip

    2011-01-01

    Membrane microdomains or lipid rafts are known to be highly dynamic and to act as selective signal transduction mediators that facilitate interactions between the cell’s external and internal environments. Lipid rafts play an important mediating role in the biology of cancer: they have been found in almost all existing experimental cancer models, including colorectal cancer (CRC), and play key regulatory roles in cell migration, metastasis, cell survival and tumor progression. This paper expl...

  6. Precision Nutrition for Targeting Lipid Metabolism in Colorectal Cancer

    Directory of Open Access Journals (Sweden)

    Cristina Aguirre-Portolés

    2017-09-01

    Full Text Available Cancer is a multistage and multifactorial condition with genetic and environmental factors modulating tumorogenesis and disease progression. Nevertheless, cancer is preventable, as one third of cancer deaths could be avoided by modifying key risk factors. Nutrients can directly affect fundamental cellular processes and are considered among the most important risk factors in colorectal cancer (CRC. Red and processed meat, poultry consumption, fiber, and folate are the best-known diet components that interact with colorectal cancer susceptibility. In addition, the direct association of an unhealthy diet with obesity and dysbiosis opens new routes in the understanding of how daily diet nutrients could influence cancer prognosis. In the “omics” era, traditional nutrition has been naturally evolved to precision nutrition where technical developments have contributed to a more accurate discipline. In this sense, genomic and transcriptomic studies have been extensively used in precision nutrition approaches. However, the relation between CRC carcinogenesis and nutrition factors is more complex than originally expected. Together with classical diet-nutrition-related genes, nowadays, lipid-metabolism-related genes have acquired relevant interest in precision nutrition studies. Lipids regulate very diverse cellular processes from ATP synthesis and the activation of essential cell-signaling pathways to membrane organization and plasticity. Therefore, a wide range of tumorogenic steps can be influenced by lipid metabolism, both in primary tumours and distal metastasis. The extent to which genetic variants, together with the intake of specific dietary components, affect the risk of CRC is currently under investigation, and new therapeutic or preventive applications must be explored in CRC models. In this review, we will go in depth into the study of co-occurring events, which orchestrate CRC tumorogenesis and are essential for the evolution of precision

  7. Protective effects of calcium from nonfat dried milk against colon carcinogenesis in rats.

    Science.gov (United States)

    Pence, B C; Dunn, D M; Zhao, C; Patel, V; Hunter, S; Landers, M

    1996-01-01

    A number of studies have demonstrated the protective effect of dietary calcium against risk for colon cancer. The objective of this experimental study was to test the efficacy of two sources of dietary calcium, elemental calcium in the form of CaCO3 and dairy calcium as nonfat dried milk (NFDM), in colon tumor inhibition. Male weanling F344 rats were fed six test diets containing low (LF, 5%) and high (HF, 20%) levels of corn oil and low (0.5%) and high (1.0%) levels of calcium supplemented as CaCO3 or NFDM in a 2 x 3 factorial design. Tumors were induced with two weekly injections of azoxymethane at 12 mg/kg body wt. After 27 weeks on the test diets, animals were necropsied for tumor analysis. There was no difference in tumor incidence for fat or calcium source main effects, but a significant interaction was seen between fat and calcium source, with the lowest tumor incidence seen in the HF/NFDM group. Calcium compartmentalization studies demonstrated no effects of calcium on serum calcium levels but increased urinary and fecal water calcium in the higher-calcium diets. Increased dietary calcium also decreased fecal bile acid concentrations, but there was no effect on fecal water bile acids. Intermediate biomarkers of colon carcinogenesis were not affected by the dietary treatments except for fat effects on carcinogen-induced nuclear aberrations. These results indicate that source of calcium is not critical but that total dietary context may affect efficacy of calcium against colon carcinogenesis.

  8. Biochemical parameters of epidermal aging in the hairless mouse and the relationship to UV-carcinogenesis.

    Science.gov (United States)

    Black, H S; Chiang, J; Gerguis, J; Lenger, W; Thornby, J I

    1994-05-01

    Epidemiological studies suggest that the incidence of cancer increases with age in both human and animal populations and that declining physiologic condition associated with aging might be responsible. Experimentally, the reverse has been most often observed, that is, older animals appear less susceptible to the induction of UV-carcinogenesis. Thus, we examined several biochemical parameters of epidermal macromolecular synthesis in hairless mice in an effort to gain insight into the role these processes play in physiological aging and their relationship to carcinogenesis. SKh-Hr-1 hairless mice were randomized into two groups (UV-irradiated and non-irradiated controls) and were two months of age at the start of irradiation and biochemical analyses. The UV group received 0.028 sunburn units (SBUs) daily (5 days wk-1) for 16 months from 40 watt BZS-WLG lamps. Stratum corneum turnover rates (SCR), cell label index (CLI), protein, DNA and RNA synthesis, and ornithine decarboxylase (ODC) induction were determined at monthly intervals over a period of two years. There were no age-related tendencies observed in SCR. CLI increased with age. Chronic, low-dose UV had no effect upon either of these parameters. Epidermal capacity for DNA and protein synthesis increased with age from 2 months to 12-15 months at which time both parameters peaked and then began to decline. UV significantly reduced (P < 0.04) the magnitude of DNA synthetic capacity at peak periods of synthesis but had no effect upon protein synthesis. RNA synthetic rates declined with age, reaching their lowest levels at 24 months. Further, a significant reduction (P < 0.001) in ODC inducibility occurred with advancing age.(ABSTRACT TRUNCATED AT 250 WORDS)

  9. Role of human papilloma virus in the oral carcinogenesis: An Indian perspective

    Directory of Open Access Journals (Sweden)

    Chocolatewala Noureen

    2009-01-01

    Full Text Available Oral squamous cell carcinoma (OSCC is one of the most common cancers in the Indian subcontinent. Although tobacco and alcohol are the main etiologic factors for nearly three-fourth of these cancers, no definite etiologic factor can be identified in one-fourth of the cases. There is growing evidence that human papilloma virus (HPV may act as a cocarcinogen, along with tobacco, in the causation of oral cancers. The role of HPV in the etiology of anogenital cancers has been firmly established, and infection with this virus has also been shown to have prognostic significance. However, there is no clear evidence to support its involvement in oral carcinogenesis. We searched the PubMed database for all literature published from 1985 to 2008 and performed a systemic review in order to understand the relationship of HPV with oral cancers and its prevalence in various sub-sites in the oral cavity. Association of HPV is strongest for oropharyngeal cancers, especially cancers of the tonsils, followed by those of the base of tongue. High-risk HPV-16 is the predominant type; it commonly affects the younger age-groups, with males appearing to have a predisposition for infection with this strain. Its prevalence increases from normal to dysplasia and finally to cancer. HPV prevalence has been reported to be twice as high in premalignant lesions as in normal mucosa and is nearly five times higher in OSCC. The overall prevalence of HPV in OSCC ranges between 20-50%. OSCCs associated with HPV have been found to have better outcomes, being more responsive to radiotherapy and showing higher survival rates. In view of the association of HPV with OSCC, it should be worthwhile to conduct further experimental studies to elucidate its role in oral carcinogenesis.

  10. [Prevention of colorectal cancer].

    Science.gov (United States)

    Gualdrini, Ubaldo Alfredo; Sambuelli, Alicia; Barugel, Mario; Gutiérrez, Alejandro; Avila, Karina Collia

    2005-01-01

    Colorectal cancer (CRC) is the second leading cause of cancer death in Argentina. The cumulative lifetime risk of developing CRC for both men and women is 4-6%. Despite advances in the management of this disease, the 5-year survival rate is about 60% because only 35% of patients are diagnosed when the disease is localized. Risk factors for CRC include age, diet and life style factors, personal or family history of adenomas or CRC and personal history of inflammatory bowel disease. Scientific evidence shows that primary and secondary prevention, through screening programs, permit to reduce incidence and mortality significantly. Chemopreventive agents, including nonsteroidal antiinflammatory drugs, folate, and calcium, have been shown to have some preventive effect. Physical inactivity and excess body weight are consistent risk factors for CRC. Tobacco exposure, diet high in red meat and low in vegetables and alcohol consumption, probably in combination with a diet low in folate, appear to increase risk. The dietary fiber and risk of CRC has been studied but the results are still inconclusive. Screening for CRC is cost-effective compared with no screening, but a single optimal strategy cannot be determined from the currently available data. The advantages and disadvantages or limitations of screening modalities for CRC are analyzed. The literature and clinical practice guidelines are reviewed, with an emphasis on advances and evolving screening methods and recommendations for patients with average, moderate and high-risk CRC.

  11. Epigenetics and colorectal cancer.

    Science.gov (United States)

    Lao, Victoria Valinluck; Grady, William M

    2011-10-18

    Colorectal cancer (CRC) is a leading cause of cancer deaths worldwide. It results from an accumulation of genetic and epigenetic changes in colon epithelial cells, which transforms them into adenocarcinomas. Over the past decade, major advances have been made in understanding cancer epigenetics, particularly regarding aberrant DNA methylation. Assessment of the colon cancer epigenome has revealed that virtually all CRCs have aberrantly methylated genes and that the average CRC methylome has hundreds to thousands of abnormally methylated genes. As with gene mutations in the cancer genome, a subset of these methylated genes, called driver genes, is presumed to have a functional role in CRC. The assessment of methylated genes in CRCs has also revealed a unique molecular subgroup of CRCs called CpG island methylator phenotype (CIMP) cancers; these tumors have a particularly high frequency of methylated genes. These advances in our understanding of aberrant methylation in CRC have led to epigenetic alterations being developed as clinical biomarkers for diagnostic, prognostic and therapeutic applications. Progress in this field suggests that these epigenetic alterations will be commonly used in the near future to direct the prevention and treatment of CRC.

  12. Lysyl oxidase in colorectal cancer

    DEFF Research Database (Denmark)

    Cox, Thomas R; Erler, Janine T

    2013-01-01

    Colorectal cancer is the third most prevalent form of cancer worldwide and fourth-leading cause of cancer-related mortality, leading to ~600,000 deaths annually, predominantly affecting the developed world. Lysyl oxidase is a secreted, extracellular matrix-modifying enzyme previously suggested...... to act as a tumor suppressor in colorectal cancer. However, emerging evidence has rapidly implicated lysyl oxidase in promoting metastasis of solid tumors and in particular colorectal cancer at multiple stages, affecting tumor cell proliferation, invasion, and angiogenesis. This emerging research has...... stimulated significant interest in lysyl oxidase as a strong candidate for developing and deploying inhibitors as functional efficacious cancer therapeutics. In this review, we discuss the rapidly expanding body of knowledge concerning lysyl oxidase in solid tumor progression, highlighting recent...

  13. Danish Colorectal Cancer Group Database

    DEFF Research Database (Denmark)

    Ingeholm, Peter; Gögenur, Ismail; Iversen, Lene H

    2016-01-01

    AIM OF DATABASE: The aim of the database, which has existed for registration of all patients with colorectal cancer in Denmark since 2001, is to improve the prognosis for this patient group. STUDY POPULATION: All Danish patients with newly diagnosed colorectal cancer who are either diagnosed......, and other pathological risk factors. DESCRIPTIVE DATA: The database has had >95% completeness in including patients with colorectal adenocarcinoma with >54,000 patients registered so far with approximately one-third rectal cancers and two-third colon cancers and an overrepresentation of men among rectal...... cancer patients. The stage distribution has been more or less constant until 2014 with a tendency toward a lower rate of stage IV and higher rate of stage I after introduction of the national screening program in 2014. The 30-day mortality rate after elective surgery has been reduced from >7% in 2001...

  14. Colorectal endoscopic mucosal resection (EMR).

    Science.gov (United States)

    Kandel, Pujan; Wallace, Michael B

    2017-08-01

    Colonoscopy has the benefit of detecting and treating precancerous adenomatous polyps and thus reduces mortality associated with CRC. Screening colonoscopy is the keystone for prevention of colorectal cancer. Over the last 20 years there has been increased in the management of large colorectal polyps from surgery to endoscopic removal techniques which is less invasive. Traditionally surgical resection was the treatment of choice for many years for larger polyps but colectomy poses significant morbidity of 14-46% and mortality of up to 7%. There are several advantages of endoscopic resection technique over surgery; it is less invasive, less expensive, has rapid recovery, and preserves the normal gut functions. In addition patient satisfaction and efficacy of EMR is higher with minor complications. Thus, this has facilitated the development of advanced resection technique for the treatment of large colorectal polyps called as endoscopic mucosal resection (EMR). Copyright © 2017 Elsevier Ltd. All rights reserved.

  15. Familial colorectal cancer type X

    DEFF Research Database (Denmark)

    Dominguez-Valentin, Mev; Therkildsen, Christina; Da Silva, Sabrina

    2015-01-01

    Heredity is a major cause of colorectal cancer, but although several rare high-risk syndromes have been linked to disease-predisposing mutations, the genetic mechanisms are undetermined in the majority of families suspected of hereditary cancer. We review the clinical presentation, histopathologi...... features, and the genetic and epigenetic profiles of the familial colorectal cancer type X (FCCTX) syndrome with the aim to delineate tumor characteristics that may contribute to refined diagnostics and optimized tumor prevention.......Heredity is a major cause of colorectal cancer, but although several rare high-risk syndromes have been linked to disease-predisposing mutations, the genetic mechanisms are undetermined in the majority of families suspected of hereditary cancer. We review the clinical presentation, histopathologic...

  16. Methylation Analysis of DNA Mismatch Repair Genes Using DNA Derived from the Peripheral Blood of Patients with Endometrial Cancer: Epimutation in Endometrial Carcinogenesis

    Directory of Open Access Journals (Sweden)

    Takashi Takeda

    2016-10-01

    Full Text Available Germline mutation of DNA mismatch repair (MMR genes is a cause of Lynch syndrome. Methylation of MutL homolog 1 (MLH1 and MutS homolog 2 (MSH2 has been detected in peripheral blood cells of patients with colorectal cancer. This methylation is referred to as epimutation. Methylation of these genes has not been studied in an unselected series of endometrial cancer cases. Therefore, we examined methylation of MLH1, MSH2, and MSH6 promoter regions of peripheral blood cells in 206 patients with endometrial cancer using a methylation-specific polymerase chain reaction (MSP. Germline mutation of MMR genes, microsatellite instability (MSI, and immunohistochemistry (IHC were also analyzed in each case with epimutation. MLH1 epimutation was detected in a single patient out of a total of 206 (0.49%—1 out of 58 (1.72% with an onset age of less than 50 years. The patient with MLH1 epimutation showed high level MSI (MSI-H, loss of MLH1 expression and had developed endometrial cancer at 46 years old, complicated with colorectal cancer. No case had epimutation of MSH2 or MSH6. The MLH1 epimutation detected in a patient with endometrial cancer may be a cause of endometrial carcinogenesis. This result indicates that it is important to check epimutation in patients with endometrial cancer without a germline mutation of MMR genes.

  17. Small non-coding RNA deregulation in endometrial carcinogenesis.

    Science.gov (United States)

    Ravo, Maria; Cordella, Angela; Rinaldi, Antonio; Bruno, Giuseppina; Alexandrova, Elena; Saggese, Pasquale; Nassa, Giovanni; Giurato, Giorgio; Tarallo, Roberta; Marchese, Giovanna; Rizzo, Francesca; Stellato, Claudia; Biancardi, Rossella; Troisi, Jacopo; Di Spiezio Sardo, Attilio; Zullo, Fulvio; Weisz, Alessandro; Guida, Maurizio

    2015-03-10

    Small non-coding RNAs (sncRNAs) represent a heterogeneous group of <200nt-long transcripts comprising microRNAs, PIWI-interacting RNAs (piRNAs) and small-nucleolar-RNAs (snoRNAs) involved in physiological and pathological processes such as carcinogenesis and tumor progression. Aberrant sncRNA expression in cancer has been associated with specific clinical phenotypes, grading, staging, metastases development and resistance to therapy.Aim of the present work is to study the role of sncRNAs in endometrial carcinogenesis. Changes in sncRNA expression were identified by high-throughput genomic analysis of paired normal, hyperplastic and cancerous endometrial tissues obtained by endometrial biopsies (n = 10). Using smallRNA sequencing and microarrays we identified significant differences in sncRNA expression pattern between normal, hyperplastic and neoplastic endometrium. This led to the definition of a sncRNA signature (129 microRNAs, 2 of which not previously described, 10 piRNAs and 3 snoRNAs) of neoplastic transformation. Functional bioinformatics analysis identified as downstream targets multiple signaling pathways potentially involved in the hyperplastic and neoplastic tissue responses, including Wnt/β-catenin, and ERK/MAPK and TGF-β-Signaling.Considering the regulatory role of sncRNAs, this newly identified sncRNA signature is likely to reflect the events leading to endometrial cancer, which can be exploited to dissect the carcinogenic process including novel biomarkers for early and non-invasive diagnosis of these tumors.

  18. Glutaminolysis and carcinogenesis of oral squamous cell carcinoma.

    Science.gov (United States)

    Cetindis, Marcel; Biegner, Thorsten; Munz, Adelheid; Teriete, Peter; Reinert, Siegmar; Grimm, Martin

    2016-02-01

    Glutaminolysis is a crucial factor for tumor metabolism in the carcinogenesis of several tumors but has not been clarified for oral squamous cell carcinoma (OSCC) yet. Expression of glutaminolysis-related solute carrier family 1, member 5 (SLC1A5)/neutral amino acid transporter (ASCT2), glutaminase (GLS), and glutamate dehydrogenase (GLDH) was analyzed in normal oral mucosa (n = 5), oral precursor lesions (simple hyperplasia, n = 11; squamous intraepithelial neoplasia, SIN I-III, n = 35), and OSCC specimen (n = 42) by immunohistochemistry. SLC1A5/ASCT2 and GLS were significantly overexpressed in the carcinogenesis of OSCC compared with normal tissue, while GLDH was weakly detected. Compared with SIN I-III SLC1A5/ASCT2 and GLS expression were significantly increased in OSCC. GLDH expression did not significantly differ from SIN I-III compared with OSCC. This study shows the first evidence of glutaminolysis-related SLC1A5/ASCT2, GLS, and GLDH expression in OSCC. The very weak GLDH expression indicates that glutamine metabolism is rather related to nucleotide or protein/hexosamine biosynthesis or to the function as an antioxidant (glutathione) than to energy production or generation of lactate through entering the tricarboxylic acid cycle. Overcoming glutaminolysis by targeting c-Myc oncogene (e.g. by natural compounds) and thereby cross-activation of mammalian target of rapamycin complex 1 or SLC1A5/ASCT2, GLS inhibitors may be a useful strategy to sensitize cancer cells to common OSCC cancer therapies.

  19. The malignant conversion step of mouse skin carcinogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Yuspa, S.H.; Hennings, H.; Roop, D.; Strickland, J.; Greenhalgh, D.A. (National Cancer Institute, Bethesda, MD (USA))

    1990-08-01

    Multiple benign squamous papillomas commonly precede the development of an occasional squamous cell carcinoma in mouse skin carcinogenesis. The incidence of carcinomas can be enhanced by treating papilloma-bearing mice with mutagens such as urethane, nitroquinoline-N-oxide, or cisplatinum. This observation suggests that a genetic change is required for malignant conversion. The malignant phenotype is characterized by a marked reduction in the transcription of specific epidermal differentiation markers, a pattern which is useful for the early diagnosis of malignant conversion. Cells expressing a benign phenotype can be obtained by introducing the v-ras{sup Ha} oncogene into cultured epidermal cells by a replication-defective retrovirus. Alternatively, benign tumor cells can be cultured from papillomas induced by chemical carcinogens in vivo or from carcinogen-treated mouse epidermis. In all cases, the benign phenotype in vitro is characterized by an altered biological response to changes in extracellular calcium, an important determinant of the differentiation state of cultured normal keratinocytes. Transfection of cloned plasmid DNA into benign tumor cells has revealed that transforming constructs of the fos oncogene induce malignant conversion, whereas myc and adenovirus E1A oncogenes do not. Cultured normal epidermal cells, exposed to the v-ras and the v-fos oncogenes simultaneously, are malignantly transformed. Alone, the fos oncogene does not detectably alter the phenotype of normal keratinocytes. These studies indicate that a limited number of genes is involved in epidermal carcinogenesis.

  20. E-cadherin: Its dysregulation in carcinogenesis and clinical implications.

    Science.gov (United States)

    Wong, Sonia How Ming; Fang, Chee Mun; Chuah, Lay-Hong; Leong, Chee Onn; Ngai, Siew Ching

    2018-01-01

    E-cadherin is a transmembrane glycoprotein which connects epithelial cells together at adherens junctions. In normal cells, E-cadherin exerts its tumour suppressing role mainly by sequestering β-catenin from its binding to LEF (Lymphoid enhancer factor)/TCF (T cell factor) which serves the function of transcribing genes of the proliferative Wnt signaling pathway. Despite the ongoing debate on whether the loss of E-cadherin is the cause or effect of epithelial-mesenchymal transition (EMT), E-cadherin functional loss has frequently been associated with poor prognosis and survival in patients of various cancers. The dysregulation of E-cadherin expression that leads to carcinogenesis happens mostly at the epigenetic level but there are cases of genetic alterations as well. E-cadherin expression has been linked to the cellular functions of invasiveness reduction, growth inhibition, apoptosis, cell cycle arrest and differentiation. Studies on various cancers have shown that these different cellular functions are also interdependent. Recent studies have reported a rapid expansion of E-cadherin clinical relevance in various cancers. This review article summarises the multifaceted effect E-cadherin expression has on cellular functions in the context of carcinogenesis as well as its clinical implications in diagnosis, prognosis and therapeutics. Copyright © 2017 Elsevier B.V. All rights reserved.

  1. Thioredoxin and metallothionein: Homeostasis-related proteins in lip carcinogenesis.

    Science.gov (United States)

    Caldeira, Patrícia C; Silva, Laíssa S; Batista, Aline C; Aguiar, Maria Cássia F

    2017-05-01

    Thioredoxin (Trx) and metallothionein (MT) are involved in the development of some carcinomas; however, the role of these proteins in labial carcinogenesis has not yet been tested. The aims of the study were to evaluate and to correlate the immunoexpression of Trx and MT in actinic cheilitis, lip squamous cell carcinoma, and normal vermillion lip mucosa. Immunohistochemistry was undertaken for Trx and MT in samples of actinic cheilitis, lip squamous cell carcinoma, and normal lip mucosa. Qualitative and semi-quantitative evaluations were conducted. The proportion of stained cells, intensity of staining, and the cell compartment labeled were evaluated. A quickscore index was also calculated by multiplying the values of extension and intensity of nuclear and cytoplasmic staining, respectively, giving a maximum value of 9. Statistics were performed. A remarkable nuclear Trx staining was seen in normal lip mucosa and cheilitis, not in carcinoma (p0.05). MT was broadly expressed in nuclei and cytoplasm of carcinoma, but not in normal lip mucosa and cheilitis (p<0.05). Quickscores were in accordance with the qualitative results. The current study showed a different immunopattern of Trx and MT between normal lip mucosa, actinic cheilitis and lip squamous cell carcinoma. The cellular compartment-based analyses evidenced differences that can be related to the proteins function. Considering the relevant roles of these proteins in cellular homeostasis, they seem to have an important role in lip carcinogenesis. Copyright © 2017 Elsevier Ltd. All rights reserved.

  2. Viral Carcinogenesis: Factors Inducing DNA Damage and Virus Integration

    Directory of Open Access Journals (Sweden)

    Yan Chen

    2014-10-01

    Full Text Available Viruses are the causative agents of 10%–15% of human cancers worldwide. The most common outcome for virus-induced reprogramming is genomic instability, including accumulation of mutations, aberrations and DNA damage. Although each virus has its own specific mechanism for promoting carcinogenesis, the majority of DNA oncogenic viruses encode oncogenes that transform infected cells, frequently by targeting p53 and pRB. In addition, integration of viral DNA into the human genome can also play an important role in promoting tumor development for several viruses, including HBV and HPV. Because viral integration requires the breakage of both the viral and the host DNA, the integration rate is believed to be linked to the levels of DNA damage. DNA damage can be caused by both endogenous and exogenous factors, including inflammation induced by either the virus itself or by co-infections with other agents, environmental agents and other factors. Typically, cancer develops years to decades following the initial infection. A better understanding of virus-mediated carcinogenesis, the networking of pathways involved in transformation and the relevant risk factors, particularly in those cases where tumorigenesis proceeds by way of virus integration, will help to suggest prophylactic and therapeutic strategies to reduce the risk of virus-mediated cancer.

  3. Bisphenol A as epigenetic modulator: setting the stage for carcinogenesis?

    Science.gov (United States)

    Ferreira, Luciana L; Couto, Renata; Oliveira, Paulo J

    2015-01-01

    Bisphenol A (BPA) is one of the most widely produced chemicals worldwide and is often used in the production of food and beverage containers. As a result of BPA contact with food, drink and toiletries, its ingestion and absorption by humans has been growing. The industrialization and modern lifestyles brought a constant exposure to several health-disturbing compounds and ushered a new era of chronic diseases. The endocrine disruptor potential of BPA is well known, but the research around its epigenotoxic effects raised further concerns whether chronic exposure to BPA can contribute to chronic human illness, including cancer in hormone-sensitive organs. Focusing on computerized databases, we reviewed original and review articles which elucidate and link some of the information already available about BPA and related epigenetic alterations. A number of studies indicate that short-term administration of low or high-doses of BPA may be associated with an increased risk of epigenetic modifications, increasing the risk for carcinogenesis. However, it is clear that more studies considering real daily exposures are essential to define a real tolerable daily intake and to tighten up manufactory regulations. In this review, we highlight some evidences suggesting a relationship between BPA exposure, genotoxic activity and epigenetic modifications, which may prime for carcinogenesis. © 2015 Stichting European Society for Clinical Investigation Journal Foundation.

  4. Sewage sludge does not induce genotoxicity and carcinogenesis

    Science.gov (United States)

    Silva, Paula Regina Pereira; Barbisan, Luis Fernando; Dagli, Maria Lúcia Zaidan; Saldiva, Paulo Hilário Nascimento

    2012-01-01

    Through a series of experiments, the genotoxic/mutagenic and carcinogenic potential of sewage sludge was assessed. Male Wistar rats were randomly assigned to four groups: Group 1 - negative control; Group 2 - liver carcinogenesis initiated by diethylnitrosamine (DEN; 200 mg/kg i.p.); Group 3 and G4-liver carcinogenesis initiated by DEN and fed 10,000 ppm or 50,000 ppm of sewage sludge. The animals were submitted to a 70% partial hepatectomy at the 3rd week. Livers were processed for routine histological analysis and immunohistochemistry, in order to detect glutathione S-transferase positive altered hepatocyte foci (GST-P+ AHF). Peripheral blood samples for the comet assay were obtained from the periorbital plexus immediately prior to sacrificing. Polychromatic erythrocytes (PCEs) were analyzed in femoral bone-marrow smears, and the frequencies of those micronucleated (MNPCEs) registered. There was no sewage-sludge-induced increase in frequency of either DNA damage in peripheral blood leucocytes, or MNPCEs in the femoral bone marrow. Also, there was no increase in the levels of DNA damage, in the frequency of MNPCEs, and in the development of GST-P AHF when compared with the respective control group. PMID:23055806

  5. Diet-induced obesity elevates colonic TNF-α in mice and is accompanied by an activation of Wnt signaling: a mechanism for obesity-associated colorectal cancer✩

    Science.gov (United States)

    Liu, Zhenhua; Brooks, Ryan S.; Ciappio, Eric D.; Kim, Susan J.; Crott, Jimmy W.; Bennett, Grace; Greenberg, Andrew S.; Mason, Joel B.

    2014-01-01

    Inflammation associated with obesity may play a role in colorectal carcinogenesis, but the underlying mechanism remains unclear. This study investigated whether the Wnt pathway, an intracellular signaling cascade that plays a critical role in colorectal carcinogenesis, is activated by obesity-induced elevation of the inflammatory cytokine tumor necrosis factor-alpha (TNF-α). Animal studies were conducted on C57BL/6 mice, and obesity was induced by utilizing a high-fat diet (60% kcal). An inflammation-specific microarray was performed, and results were confirmed with real-time polymerase chain reaction. The array revealed that diet-induced obesity increased the expression of TNF-α in the colon by 72% (P=.004) and that of interleukin-18 by 41% (P=.023). The concentration of colonic TNF-α protein, determined by ex vivo culture assay, was nearly doubled in the obese animals (P=.002). The phosphorylation of glycogen synthase kinase 3 beta (GSK3β), an important intermediary inhibitor of Wnt signaling and a potential target of TNF-α, was quantitated by immunohistochemistry. The inactivated (phosphorylated) form of GSK3β was elevated in the colonic mucosa of obese mice (Pobese mice (Pobesity produces an elevation in colonic TNF-α and instigates a number of alterations of key components within the Wnt signaling pathway that are protransformational in nature. Thus, these observations offer evidence for a biologically plausible avenue, the Wnt pathway, by which obesity increases the risk of colorectal cancer. PMID:22209007

  6. Probiotics, prebiotics and colorectal cancer prevention.

    Science.gov (United States)

    Ambalam, Padma; Raman, Maya; Purama, Ravi Kiran; Doble, Mukesh

    2016-02-01

    Colorectal cancer (CRC), the third major cause of mortality among various cancer types in United States, has been increasing in developing countries due to varying diet and dietary habits and occupational hazards. Recent evidences showed that composition of gut microbiota could be associated with the development of CRC and other gut dysbiosis. Modulation of gut microbiota by probiotics and prebiotics, either alone or in combination could positively influence the cross-talk between immune system and microbiota, would be beneficial in preventing inflammation and CRC. In this review, role of probiotics and prebiotics in the prevention of CRC has been discussed. Various epidemiological and experimental studies, specifically gut microbiome research has effectively improved the understanding about the role of probiotics and microbial treatment as anticarcinogenic agents. A few human studies support the beneficial effect of probiotics and prebiotics; hence, comprehensive understanding is urgent to realize the clinical applications of probiotics and prebiotics in CRC prevention. Copyright © 2016 Elsevier Ltd. All rights reserved.

  7. Ras gene mutation is not related to tumour invasion during rat tongue carcinogenesis induced by 4-nitroquinoline 1-oxide.

    Science.gov (United States)

    Fracalossi, Ana C C; Comparini, Larissa; Funabashi, Karina; Godoy, Carla; Iwamura, Edna S M; Nascimento, Fábio D; Nader, Helena B; Oshima, Celina T F; Ribeiro, Daniel A

    2011-04-01

    The aim of this study was to investigate whether mutations in the genes H-ras and K-ras were related to the mechanism of invasion as a result of the immunoexpression of H-Ras, Ki-67, alpha-smooth muscle actin (SMA) and vascular endothelial growth factor (VEGF) during 4-nitroquinoline 1-oxide (4NQO)-induced rat tongue carcinogenesis. Male Wistar rats were distributed into three groups of 10 animals each and treated with 50 ppm 4NQO solution through their drinking water for 4, 12 and 20 weeks. Ten animals were used as negative control. Although no histopathological abnormalities were induced in the epithelium after 4 weeks of carcinogen exposure, Ki-67 was overexpresssed in the 'normal' oral epithelium. In pre-neoplastic lesions at 12 weeks following carcinogen exposure, the levels of Ki-67 were increased (P 0.05) were found in H-ras protein expression for all experimental periods evaluated that corresponded to normal oral mucosa, hyperplasia, dysplasia and squamous cell carcinomas. In the same way, no mutations in H-ras or K-ras genes were found. Our results support the idea that expression of Ki-67 plays a crucial role during malignant transformation being closely related to neoplastic conversion of the oral mucosa cells. However, it seems that mutations in the ras genes are not involved to experimental tongue carcinogenesis induced by 4NQO. © 2011 John Wiley & Sons A/S.

  8. Institutional Animal Care and Use Committee Considerations Regarding the Use of Virus-Induced Carcinogenesis and Oncolytic Viral Models.

    Science.gov (United States)

    Lewis, Stephanie D; Hickman-Davis, Judy M; Bergdall, Valerie K

    2016-01-01

    The use of virus-induced carcinogenesis and oncologic experimental animal models is essential in understanding the mechanisms of cancer development to advance prevention, diagnosis, and treatment methods. The Institutional Animal Care and Use Committee (IACUC) is responsible for both the complex philosophical and practical considerations associated with animal models of cancer. Animal models of cancer carry their own unique issues that require special consideration from the IACUC. Many of the considerations to be discussed apply to cancer models in general; specific issues related to viral carcinogenesis or oncolytic viruses will be specifically discussed as they arise. Responsible animal use integrates good science, humane care, and regulatory compliance. To meet those standards, the IACUC, in conjunction with the research investigator and attending veterinarian, must address a wide range of issues, including animal model selection, cancer model selection, humane end point considerations, experimental considerations, postapproval monitoring, reporting requirements, and animal management and personnel safety considerations. © The Author 2016. Published by Oxford University Press on behalf of the Institute for Laboratory Animal Research. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  9. Colorectal cancer statistics, 2017.

    Science.gov (United States)

    Siegel, Rebecca L; Miller, Kimberly D; Fedewa, Stacey A; Ahnen, Dennis J; Meester, Reinier G S; Barzi, Afsaneh; Jemal, Ahmedin

    2017-05-06

    Colorectal cancer (CRC) is one of the most common malignancies in the United States. Every 3 years, the American Cancer Society provides an update of CRC incidence, survival, and mortality rates and trends. Incidence data through 2013 were provided by the Surveillance, Epidemiology, and End Results program, the National Program of Cancer Registries, and the North American Association of Central Cancer Registries. Mortality data through 2014 were provided by the National Center for Health Statistics. CRC incidence rates are highest in Alaska Natives and blacks and lowest in Asian/Pacific Islanders, and they are 30% to 40% higher in men than in women. Recent temporal patterns are generally similar by race and sex, but differ by age. Between 2000 and 2013, incidence rates in adults aged ≥50 years declined by 32%, with the drop largest for distal tumors in people aged ≥65 years (incidence rate ratio [IRR], 0.50; 95% confidence interval [95% CI], 0.48-0.52) and smallest for rectal tumors in ages 50 to 64 years (male IRR, 0.91; 95% CI, 0.85-0.96; female IRR, 1.00; 95% CI, 0.93-1.08). Overall CRC incidence in individuals ages ≥50 years declined from 2009 to 2013 in every state except Arkansas, with the decrease exceeding 5% annually in 7 states; however, rectal tumor incidence in those ages 50 to 64 years was stable in most states. Among adults aged history of CRC/advanced adenomas) and eliminating disparities in high-quality treatment. In addition, research is needed to elucidate causes for increasing CRC in young adults. CA Cancer J Clin 2017. © 2017 American Cancer Society. CA Cancer J Clin 2017;67:177-193. © 2017 American Cancer Society. © 2017 American Cancer Society.

  10. Keratins in colorectal epithelial function and disease.

    Science.gov (United States)

    Majumdar, Debabrata; Tiernan, James P; Lobo, Alan J; Evans, Caroline A; Corfe, Bernard M

    2012-10-01

    Keratins are the largest subgroup of intermediate filament proteins, which are an important constituent of the cellular cytoskeleton. The principally expressed keratins (K) of the intestinal epithelium are K8, K18 and K19. The specific keratin profile of a particular epithelium provides it with strength and integrity. In the colon, keratins have been shown to regulate electrolyte transport, likely by targeting ion transporters to their correct location in the colonocytes. Keratins are highly dynamic and are subject to post-translational modifications including phosphorylation, acetylation and glycosylation. These affect the filament dynamics and hence solubility of keratins and may contribute to protection against degradation. Keratin null mice (K8(-/-) ) develop colitis, and abnormal keratin mutations have been shown to be associated with inflammatory bowel disease (IBD). Abnormal expression of K7 and K20 has been noted in colitis-associated dysplasia and cancers. In sporadic colorectal cancers (CRCs) may be useful in predicting tumour prognosis; a low K20 expression is noted in CRCs with high microsatellite instability; and keratins have been noted as dysregulated in peri-adenomatous fields. Caspase-cleaved fragment of K18 (M30) in the serum of patients with CRC has been used as a marker of cancer load and to assess response to therapy. These data suggest an emerging importance of keratins in maintaining normal function of the gastrointestinal epithelium as well as being a marker of various colorectal diseases. This review will primarily focus on the biology of these proteins, physiological functions and alterations in IBD and CRCs. © 2012 The Authors. International Journal of Experimental Pathology © 2012 International Journal of Experimental Pathology.

  11. Dietary tomato and lycopene impact androgen signaling- and carcinogenesis-related gene expression during early TRAMP prostate carcinogenesis

    Science.gov (United States)

    Wan, Lei; Tan, Hsueh-Li; Thomas-Ahner, Jennifer M.; Pearl, Dennis K.; Erdman, John W.; Moran, Nancy E.; Clinton, Steven K.

    2014-01-01

    Consumption of tomato products containing the carotenoid lycopene is associated with a reduced risk of prostate cancer. To identify gene expression patterns associated with early testosterone-driven prostate carcinogenesis, which are impacted by dietary tomato and lycopene, wild type (WT) and transgenic adenocarcinoma of the mouse prostate (TRAMP) mice were fed control or tomato- or lycopene-containing diets from 4-10 wk-of-age. Eight-week-old mice underwent sham surgery, castration, or castration followed by testosterone-repletion (2.5 mg/kg/d initiated 1 wk after castration). Ten-wk-old intact TRAMP mice exhibit early multifocal prostatic intraepithelial neoplasia (PIN). Of the 200 prostate cancer-related genes measured by quantitative NanoString®, 189 are detectable, 164 significantly differ by genotype, 179 by testosterone status, and 30 by diet type (Plycopene feeding (Srd5a1) and by tomato-feeding (Srd5a2, Pxn, and Srebf1). Additionally, tomato-feeding significantly reduced expression of genes associated with stem cell features, Aldh1a and Ly6a, while lycopene-feeding significantly reduced expression of neuroendocrine differentiation-related genes, Ngfr and Syp. Collectively, these studies demonstrate a profile of testosterone-regulated genes associated with early stages of prostate carcinogenesis that are potential mechanistic targets of dietary tomato components. Future studies on androgen signaling/metabolism, stem cell features, and neuroendocrine differentiation pathways may elucidate the mechanisms by which dietary tomato and lycopene impact prostate cancer risk. PMID:25315431

  12. Epithelial-mesenchymal transition and its role in the pathogenesis of colorectal cancer.

    Science.gov (United States)

    Zhu, Qing-Chao; Gao, Ren-Yuan; Wu, Wen; Qin, Huan-Long

    2013-01-01

    Epithelial-to-mesenchymal transition (EMT) is a collection of events that allows the conversion of adherent epithelial cells, tightly bound to each other within an organized tissue, into independent fibroblastic cells possessing migratory properties and the ability to invade the extracellular matrix. EMT contributes to the complex architecture of the embryo by permitting the progression of embryogenesis from a simple single-cell layer epithelium to a complex three-dimensional organism composed of both epithelial and mesenchymal cells. However, in most tissues EMT is a developmentally restricted process and fully differentiated epithelia typically maintain their epithelial phenotype. Recently, elements of EMT, specially the loss of epithelial markers and the gain of mesenchymal markers, have been observed in pathological states, including epithelial cancers. Increasing evidence has confirmed its presence in human colon during colorectal carcinogenesis. In general, chronic inflammation is considered to be one of the causes of many human cancers including colorectal cancer(CRC). Accordingly, epidemiologic and clinical studies indicate that patients affected by ulcerative colitis and Crohn's disease, the two major forms of inflammatory bowel disease, have an increased risk of developing CRC. A large body of evidence supports roles for the SMAD/STAT3 signaling pathway, the NF-kB pathway, the Ras-mitogen- activated protein kinase/Snail/Slug and microRNAs in the development of colorectal cancers via epithelial-to- mesenchymal transition. Thus, EMT appears to be closely involved in the pathogenesis of colorectal cancer, and analysis refered to it can yield novel targets for therapy.

  13. Microscopic colitis and colorectal neoplastic lesion rate in chronic nonbloody diarrhea: a prospective, multicenter study.

    Science.gov (United States)

    Tontini, Gian Eugenio; Pastorelli, Luca; Spina, Luisa; Fabris, Federica; Bruni, Barbara; Clemente, Claudio; de Nucci, Germana; Cavallaro, Flaminia; Marconi, Stefano; Neurath, Markus F; Neumann, Helmut; Tacconi, Milena; Vecchi, Maurizio

    2014-05-01

    Lymphocytic and collagenous colitis are emerging as common findings in subjects undergoing colonoscopy for chronic non-bloody diarrhea (CNBD). Data concerning microscopic colitis (MC) are still limited and affected by controversial epidemiological evidences. Recent converging lines of evidence suggest that MC correlates a lower risk of colorectal neoplasia. Accordingly, we prospectively assessed MC prevalence in a multicenter cohort of subjects submitted to colonoscopy for CNBD, thereby defining whether MC influences the risk of colorectal neoplasia. Consecutive patients with CNBD of unknown origin underwent pan-colonoscopy with multiple biopsies. The prevalence of neoplastic patients in MC was compared with that observed in negative CNBD subjects. Among 8006 colonoscopy, 305 subjects were enrolled for CNBD. Patients with CNBD were more likely to be women than men (odds ratio = 1.5; P = 0.001). Histopathology detected high prevalence of MC (16%) with a clear predominance of collagenous colitis (70%). A striking age-dependent rise in MC-associated risk was observed, depicting outstanding differences among varying age groups, as in the number needed to screen 1 new case. Gender distribution was balanced within MC patients (Female/Male = 1.5/1), especially among lymphocytic colitis (Female/Male = 1.2/1). MC patients were negatively associated with the risk of neoplastic polyps compared with negative CNBD subjects (odds ratio = 0.22; P = 0.035). MC is the first cause of CNBD in subjects submitted to colonoscopy. Multiple biopsies are strongly recommended, even in the case of uneventful endoscopic inspection, especially for age ≥40 years. MC has a reduced risk of colorectal neoplasia, suggesting that this model of chronic inflammation plays a protective effect against colorectal carcinogenesis.

  14. Novel mouse model recapitulates genome and transcriptome alterations in human colorectal carcinomas.

    Science.gov (United States)

    McNeil, Nicole E; Padilla-Nash, Hesed M; Buishand, Floryne O; Hue, Yue; Ried, Thomas

    2017-03-01

    Human colorectal carcinomas are defined by a nonrandom distribution of genomic imbalances that are characteristic for this disease. Often, these imbalances affect entire chromosomes. Understanding the role of these aneuploidies for carcinogenesis is of utmost importance. Currently, established transgenic mice do not recapitulate the pathognonomic genome aberration profile of human colorectal carcinomas. We have developed a novel model based on the spontaneous transformation of murine colon epithelial cells. During this process, cells progress through stages of pre-immortalization, immortalization and, finally, transformation, and result in tumors when injected into immunocompromised mice. We analyzed our model for genome and transcriptome alterations using ArrayCGH, spectral karyotyping (SKY), and array based gene expression profiling. ArrayCGH revealed a recurrent pattern of genomic imbalances. These results were confirmed by SKY. Comparing these imbalances with orthologous maps of human chromosomes revealed a remarkable overlap. We observed focal deletions of the tumor suppressor genes Trp53 and Cdkn2a/p16. High-level focal genomic amplification included the locus harboring the oncogene Mdm2, which was confirmed by FISH in the form of double minute chromosomes. Array-based global gene expression revealed distinct differences between the sequential steps of spontaneous transformation. Gene expression changes showed significant similarities with human colorectal carcinomas. Pathways most prominently affected included genes involved in chromosomal instability and in epithelial to mesenchymal transition. Our novel mouse model therefore recapitulates the most prominent genome and transcriptome alterations in human colorectal cancer, and might serve as a valuable tool for understanding the dynamic process of tumorigenesis, and for preclinical drug testing. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  15. Inflammation-Related Pancreatic Carcinogenesis: Mechanisms and Clinical Potentials in Advances.

    Science.gov (United States)

    Dai, Juan-Juan; Jiang, Ming-Jie; Wang, Xing-Peng; Tian, Ling

    2017-09-01

    Chronic inflammation has long been considered critical in pancreatic carcinogenesis, and recently studies showed that some anti-inflammatory agents such as aspirin could potentially be used to attenuate pancreatic carcinogenesis. Several inflammation-related critical transcription factors and pathways such as NF-κB (nuclear factor κ-light-chain enhancer of activated B cells) and reactive oxygen species have been confirmed to be involved in carcinogenesis. However, its underlying mechanisms are far from clear, which largely limits further development of potential anticarcinogenesis drugs. As a result, it is of great importance for us to better understand and gain a better perspective in inflammation-related pancreatic carcinogenesis. In this review, we systematically analyzed recent advances concerning inflammation-related pancreatic carcinogenesis and brought out the possible underlying mechanisms. Potential preventive and therapeutic strategies based on anti-inflammatory agents have also been further discussed.

  16. Malignant melanoma in patients with hereditary nonpolyposis colorectal cancer.

    Science.gov (United States)

    Ponti, G; Losi, L; Pellacani, G; Wannesson, L; Cesinaro, A M; Venesio, T; Petti, C; Seidenari, S

    2008-07-01

    Malignant melanoma (MM) is the most aggressive skin cancer. Most MMs are sporadic, and in this setting an association with mismatch repair (MMR) gene mutations, typical of hereditary nonpolyposis colorectal cancer (HNPCC) tumours, has been proposed. To characterize clinically and/or by molecular biology the patients with MM belonging to a cohort of 60 kindreds with HNPCC. Methods Patients with HNPCC with a diagnosis of MM were studied by immunohistochemistry (IHC) on tumour tissue using antibodies to MLH1, MSH2, p16, beta-catenin and E-cadherin, and by direct sequencing of MMR genes on germline DNA, and BRAF and NRAS on somatic DNA extracted from MM. Nine cutaneous MMs were detected in the tumour spectrum of eight families with HNPCC. The median age at diagnosis was 46 years. In one HNPCC family the diagnosis of MM was made in two first-degree relatives fitting the clinical definition of familial melanoma. IHC and sequencing analysis showed an MSH2 mutation in one patient with MM. Dermatological surveillance should be recommended to families in which MM is diagnosed in at least one member, especially at a young age. The combination of MMR gene mutations and abnormalities of p16 or other molecular pathways is needed to induce melanocytic carcinogenesis in a familial setting as well as in sporadic MM.

  17. Aberrant gene promoter methylation associated with sporadic multiple colorectal cancer.

    Directory of Open Access Journals (Sweden)

    Victoria Gonzalo

    Full Text Available BACKGROUND: Colorectal cancer (CRC multiplicity has been mainly related to polyposis and non-polyposis hereditary syndromes. In sporadic CRC, aberrant gene promoter methylation has been shown to play a key role in carcinogenesis, although little is known about its involvement in multiplicity. To assess the effect of methylation in tumor multiplicity in sporadic CRC, hypermethylation of key tumor suppressor genes was evaluated in patients with both multiple and solitary tumors, as a proof-of-concept of an underlying epigenetic defect. METHODOLOGY/PRINCIPAL FINDINGS: We examined a total of 47 synchronous/metachronous primary CRC from 41 patients, and 41 gender, age (5-year intervals and tumor location-paired patients with solitary tumors. Exclusion criteria were polyposis syndromes, Lynch syndrome and inflammatory bowel disease. DNA methylation at the promoter region of the MGMT, CDKN2A, SFRP1, TMEFF2, HS3ST2 (3OST2, RASSF1A and GATA4 genes was evaluated by quantitative methylation specific PCR in both tumor and corresponding normal appearing colorectal mucosa samples. Overall, patients with multiple lesions exhibited a higher degree of methylation in tumor samples than those with solitary tumors regarding all evaluated genes. After adjusting for age and gender, binomial logistic regression analysis identified methylation of MGMT2 (OR, 1.48; 95% CI, 1.10 to 1.97; p = 0.008 and RASSF1A (OR, 2.04; 95% CI, 1.01 to 4.13; p = 0.047 as variables independently associated with tumor multiplicity, being the risk related to methylation of any of these two genes 4.57 (95% CI, 1.53 to 13.61; p = 0.006. Moreover, in six patients in whom both tumors were available, we found a correlation in the methylation levels of MGMT2 (r = 0.64, p = 0.17, SFRP1 (r = 0.83, 0.06, HPP1 (r = 0.64, p = 0.17, 3OST2 (r = 0.83, p = 0.06 and GATA4 (r = 0.6, p = 0.24. Methylation in normal appearing colorectal mucosa from patients with multiple and solitary CRC showed no relevant

  18. Colorectal Cancer Awareness and Screening

    Centers for Disease Control (CDC) Podcasts

    2017-04-06

    An oncologist (cancer doctor) shares her medical and personal advice for people between the ages of 50 and 75 about getting screened for colorectal cancer.  Created: 4/6/2017 by National Center for Chronic Disease Prevention and Health Promotion (NCCDPHP).   Date Released: 4/6/2017.

  19. Costs of Colorectal Cancer Screening

    Centers for Disease Control (CDC) Podcasts

    2017-04-04

    A health economist talks about studies on figuring out the costs of running a colorectal cancer screening program, and how this can lead to better screening.  Created: 4/4/2017 by National Center for Chronic Disease Prevention and Health Promotion (NCCDPHP).   Date Released: 4/4/2017.

  20. Targeted nanoparticles for colorectal cancer

    DEFF Research Database (Denmark)

    Cisterna, Bruno A.; Kamaly, Nazila; Choi, Won Il

    2016-01-01

    Colorectal cancer (CRC) is highly prevalent worldwide, and despite notable progress in treatment still leads to significant morbidity and mortality. The use of nanoparticles as a drug delivery system has become one of the most promising strategies for cancer therapy. Targeted nanoparticles could...

  1. Colorectal Cancer Risk Prediction Models

    Science.gov (United States)

    Developing statistical models that estimate the probability of developing colorectal cancer over a defined period of time will help clinicians identify individuals at higher risk of specific cancers, allowing for earlier or more frequent screening and counseling of behavioral changes to decrease risk.

  2. Targeted nanoparticles for colorectal cancer

    DEFF Research Database (Denmark)

    Cisterna, Bruno A.; Kamaly, Nazila; Choi, Won Il

    2016-01-01

    Colorectal cancer (CRC) is highly prevalent worldwide, and despite notable progress in treatment still leads to significant morbidity and mortality. The use of nanoparticles as a drug delivery system has become one of the most promising strategies for cancer therapy. Targeted nanoparticles could ...

  3. Tumor budding in colorectal carcinomas.

    Science.gov (United States)

    Sert Bektaş, Sevda; Inan Mamak, Gülsün; Cırış, Ibrahim Metin; Bozkurt, Kemal Kürşat; Kapucuoğlu, Nilgün

    2012-01-01

    In colorectal carcinomas, tumor budding has been defined as the presence of isolated single tumor cells or small cell clusters in the stroma at the invasive tumor margin. In this study, the relationship between tumor budding density at the invasive tumor margin and pathological parameters is investigated. Haematoxylin and eosin stained slides of 73 cases with colorectal carcinoma were retrospectively evaluated for the presence and intensity of tumor budding by 2 observers. After the specimens were assessed, the highest density of tumor budding area was counted in a microscopic field of x200. Cases were separated into 2 groups according to tumor budding density as low grade ( tumor invasion, histological grade, vascular invasion and lymph node involvement was investigated. Of the 73 colorectal carcinoma cases, 33 (45.2%) had low and 40 (54.8%) had high grade tumor budding density, respectively. There was a statistically significant relationship between high grade tumor budding density and histological grade (p=0.042), lymph node involvement (p=0.0001) and vascular invasion (p=0.0034). High grade tumor budding density is associated with aggressive phenotypical features in colorectal carcinoma.

  4. Thromboprophylaxis among Australasian colorectal surgeons.

    Science.gov (United States)

    Smart, Philip; Burbury, Kate; Lingaratnam, Senthil; Lynch, A Craig; Mackay, John; Heriot, Alexander

    2013-09-01

    Thromboembolism is a common cause of morbidity and mortality in patients with colorectal cancer, but thromboprophylaxis (TP) is underutilized. Current guidelines do not make specific recommendations for colorectal cancer patients and provide minimal guidance for the ambulatory setting, although emerging evidence suggests TP may be warranted during chemoradiotherapy or in the extended post-operative phase. A survey of Australasian colorectal surgeons was therefore performed to assess current TP practice and attitudes. An online survey was sent to 204 surgeons who were members of the Colorectal Surgical Society of Australia and New Zealand. One hundred twenty-eight surgeons (63%) completed the survey. Most surgeons consult available guidelines, and where recommendations are made, current practice is in line with them. Lack of data, lack of ownership, logistical issues and an absence of guideline recommendations currently prevent surgeons from instituting TP in the neoadjuvant treatment period. Fifty-four per cent of surgeons currently prescribe TP after hospital discharge; those that do not, cite logistical issues as the main constraint. More data on thromboembolism risk during various treatment phases are required and should be promulgated in tumour-specific guidelines. Logistical barriers to adopting TP in the ambulatory setting should be addressed. © 2012 The Authors. ANZ Journal of Surgery © 2012 Royal Australasian College of Surgeons.

  5. Targeted deletion of Kif18a protects from colitis-associated colorectal (CAC) tumors in mice through impairing Akt phosphorylation

    Energy Technology Data Exchange (ETDEWEB)

    Zhu, Houbao [State Key Laboratory of Medical Genomics, Research Center for Experimental Medicine, Rui-Jin Hospital and Department of Medical Genetics, E-Institutes of Shanghai Universities, Shanghai Jiao Tong University School of Medicine (SJTUSM), Shanghai 200025 (China); Xu, Wangyang [Department of Clinical Laboratories, Ninth People’s Hospital, SJTUSM, Shanghai 200011 (China); Zhang, Hongxin [State Key Laboratory of Medical Genomics, Research Center for Experimental Medicine, Rui-Jin Hospital and Department of Medical Genetics, E-Institutes of Shanghai Universities, Shanghai Jiao Tong University School of Medicine (SJTUSM), Shanghai 200025 (China); Liu, Jianbing [State Key Laboratory of Medical Genomics, Research Center for Experimental Medicine, Rui-Jin Hospital and Department of Medical Genetics, E-Institutes of Shanghai Universities, Shanghai Jiao Tong University School of Medicine (SJTUSM), Shanghai 200025 (China); Shanghai Research Center for Model Organisms, Shanghai 201203 (China); Xu, Haimin [Department of Pathology, Rui-Jin Hospital, SJTUSM, Shanghai 200025 (China); Lu, Shunyuan; Dang, Suying [State Key Laboratory of Medical Genomics, Research Center for Experimental Medicine, Rui-Jin Hospital and Department of Medical Genetics, E-Institutes of Shanghai Universities, Shanghai Jiao Tong University School of Medicine (SJTUSM), Shanghai 200025 (China); Kuang, Ying [Shanghai Research Center for Model Organisms, Shanghai 201203 (China); Jin, Xiaolong [Department of Pathology, Rui-Jin Hospital, SJTUSM, Shanghai 200025 (China); Wang, Zhugang, E-mail: zhugangw@shsmu.edu.cn [State Key Laboratory of Medical Genomics, Research Center for Experimental Medicine, Rui-Jin Hospital and Department of Medical Genetics, E-Institutes of Shanghai Universities, Shanghai Jiao Tong University School of Medicine (SJTUSM), Shanghai 200025 (China); Shanghai Research Center for Model Organisms, Shanghai 201203 (China)

    2013-08-16

    Highlights: •Kif18A is up-regulated in CAC of mouse model. •Kif18a{sup −/−} mice are protected from CAC. •Tumor cells from Kif18a{sup −/−} mice undergo more apoptosis. •Kif18A deficiency induces poor Atk phosphorylation. -- Abstract: Kinesins are a superfamily of molecular motors involved in cell division or intracellular transport. They are becoming important targets for chemotherapeutic intervention of cancer due to their crucial role in mitosis. Here, we demonstrate that the kinesin-8 Kif18a is overexpressed in murine CAC and is a crucial promoter during early CAC carcinogenesis. Kif18a-deficient mice are evidently protected from AOM–DSS-induced colon carcinogenesis. Kif18A is responsible for proliferation of colonic tumor cells, while Kif18a ablation in mice promotes cell apoptosis. Mechanistically, Kif18a is responsible for induction of Akt phosphorylation, which is known to be associated with cell survival regulation. In conclusion, Kif18a is critical for colorectal carcinogenesis in the setting of inflammation by mechanisms of increased PI3K-AKT signaling. Inhibition of Kif18A activity may be useful in the prevention or chemotherapeutic intervention of CAC.

  6. HPV induced cervical carcinogenesis: molecular basis and vaccine development.

    Science.gov (United States)

    Kaufmann, A M; Backsch, C; Schneider, A; Dürst, M

    2002-11-01

    Association of infection with papillomavirus and dysplasia of the cervix uteri has been firmly established. There are only few cervical cancers where no HPV DNA is detectable. The mechanism of epithelial cell immortalization by interaction with tumour suppressor genes p53 and pRb by viral oncogenes E6 and E7 is elucidated. Progression of the HPV infected cell to a malignant phenotype involves further modification of host gene expression and/or mutations. The appearance of chromosomal aberrations can lead to mutational inactivation or loss of tumour suppressor genes (TSG), activation and amplification of oncogenes, with importance for the process of carcinogenesis. Oncogene amplification, with exception of few reports, seems not to be a major mechanism in cervical carcinogenesis. In contrast, cytogenetic and loss of heterozygosity (LOH) results from CIN and invasive cancer demonstrate alterations at specific chromosomal regions, pointing at localisation of TSG. Genetic alterations at chromosomes 3p, 6p, 1lq were frequently found early in tumour development Primary invasive carcinoma showed additional allelic losses at chromosome arms 6q, 17p and 18q. Useful biological diagnostic and prognostic markers for high-risk HPV infection and malignant progression may be p16NK4 p27Kip, and NET-I/C4.8. Putative senescence genes relevant for HPV-induced carcinogenesis are localized on chromosomes 2, 4 and 10. Genes for Telomerase suppression are presumably located on chromosomes 3, 4 and 6. Natural immune responses to HPV infection exist Therefore, immune therapy is an attractive possibility for prevention and therapy of HPV infection. To date, vaccine development has reached clinical evaluation. Prophylaxis aims at the induction of virus neutralizing antibodies to capsid proteins. Virus-like particle vaccines are currently tested in clinical trials. Due to the long lag period between infection and clinical manifestation trials will take a long time until conclusive results are

  7. HISTOMORPHOLOGICAL STUDY OF COLORECTAL MALIGNANCIES

    Directory of Open Access Journals (Sweden)

    Sarvesh

    2015-07-01

    Full Text Available BACKGROUND: Colorectal cancer is the most common cancer in men and in women worldwide. Incidence rates of colorectal cancer vary 10 - fold in both sexes worldwide, Within Asia, the incidence rates vary widely and are uniformly low in all south Asian countries and high i n all developed Asian countries. Fortunately, the age adjusted incidence rates of colorectal cancer in all the Indian cancer registries are very close to the lowest rates in the world. The present study is under taken to study the prevalence and types of c olorectal cancer among the patients in the rural population in and around Chidambaram. OBJECTIVES: To study the prevalence of malignant colorectal neoplasms among the speci mens received in the Department of Pathology and the gross and histomorphological pa ttern of the lesions and finally to correlate the findings with clinical data. METHOD: The materials consisted of 68 specimens who were submitted to the Department of Pathology, during the period of Jan 2008 - Dec 2012. Data collected and entered in MS - Excel and were analyzed using SPSS - 16. RESULTS : Out of 8454 colonoscopic specimens, 68(0.8% showed colorectal malignancy. A higher frequency of colorectal was seen in 6 th decade. Out of 68 specimens of malignant neoplasms majority were Carcinoma of the Rectum (79.41% followed in decreasing order of frequency by malignant lesions of descending colon(8.82%, ascending and Sigmoid colon (4.41% each, recto - sigmoid (2.94% and cecum (2.63%, and transverse colon (2.63%. Youngest patient was 19 years old and the o ldest patient was 80 years old with a mean age of 49.5 years and median age of 50 years. CONCLUSION: Colorectal cancer is a common and lethal disease. The adenoma carcinoma. S equence offers a window of opportunity in which the precursor lesion or early car cinoma can be removed endoscopically to prevent systematic disease. The result of a careful and systematic examination of surgical specimens from patients with

  8. Carcinogenesis and Inflammatory Effects of Plutonium-Nitrate Retention in an Exposed Nuclear Worker and Beagle Dogs.

    Energy Technology Data Exchange (ETDEWEB)

    Nielsen, Christopher E. [Pacific Northwest National Laboratory (PNNL), Richland, WA (United States); Wang, Xihai [Pacific Northwest National Laboratory (PNNL), Richland, WA (United States); Robinson, Robert J. [Pacific Northwest National Laboratory (PNNL), Richland, WA (United States); Brooks, Antone L. [Pacific Northwest National Laboratory (PNNL), Richland, WA (United States); Lovaglio, Jamie A. [Pacific Northwest National Laboratory (PNNL), Richland, WA (United States); Patton, Kristin M. [Battelle Toxicology Northwest, Richland, WA (United States); McComish, Stacey [United States Transuranium and Uranium Registries, Washington State University, College of Pharmacy, Richland, WA (United States); Tolmachev, Sergei Y. [United States Transuranium and Uranium Registries, Washington State University, College of Pharmacy, Richland, WA (United States); Morgan, William F. [Pacific Northwest National Laboratory (PNNL), Richland, WA (United States)

    2014-01-01

    The genetic and inflammatory response pathways elicited following plutonium exposure in archival lung tissue of an occupationally exposed human and experimentally exposed beagle dogs were investigated. These pathways include: tissue injury, apoptosis and gene expression modifications related to carcinogenesis and inflammation. In order to determine which pathways are involved, multiple lung samples from a plutonium exposed worker (Case 0269), a human control (Case 0385), and plutonium exposed beagle dogs were examined using histological staining and immunohistochemistry. Examinations were performed to identify target tissues at risk of radiation-induced fibrosis, inflammation, and carcinogenesis. Case 0269 showed interstitial fibrosis in peripheral and subpleural regions of the lung, but no pulmonary tumors. In contrast, the dogs with similar and higher doses showed pulmonary tumors primarily in brochiolo-alveolar, peripheral and subpleural alveolar regions. The TUNEL assay showed slight elevation of apoptosis in tracheal mucosa, tumor cells, and nuclear debris was present in the inflammatory regions of alveoli and lymph nodes of both the human and the dogs. The expression of apoptosis and a number of chemokine/cytokine genes was slightly but not significantly elevated in protein or gene levels compared to that of the control samples. In the beagles, mucous production was increased in the airway epithelial goblet cells and glands of trachea, and a number of chemokine/cytokine genes showed positive immunoreactivity. This analysis of archival tissue from an accidentally exposed worker and in a large animal model provides valuable information on the effects of long-term retention of plutonium in the respiratory tract and the histological evaluation study may impact mechanistic studies of radiation carcinogenesis.

  9. CAMK2? in Intestinal Epithelial Cells Modulates Colitis-Associated Colorectal Carcinogenesis via Enhancing STAT3 Activation

    OpenAIRE

    Ma, Xiaoxiao; Meng, Zhipeng; Jin, Lihua; Xiao, Zhenzhou; Wang, Xiaoqiong; Tsark, Walter M.; Ding, Lili; Gu, Ying; Zhang, Jiawei; Kim, Byungwook; He, Min; Gan, Xiaoxian; John E Shively; Yu, Hua; Xu, Rongzhen

    2017-01-01

    Inflammation is one of the major risk factors for cancer. Here, we show that calcium/calmodulin-dependent protein kinase II gamma (CAMK2?) in intestinal epithelial cells (IECs) modulates inflammatory signals and promotes colitis-associated cancer (CAC) in mice. We have identified CAMK2? as a downstream target of colitis-induced WNT5a signaling. Furthermore, we have shown that CAMK2? protects against intestine tissue injury by increasing IEC survival and proliferation. CAMK2? knockout mice dis...

  10. Tumor and the Microenvironment: A Chance to Reframe the Paradigm of Carcinogenesis?

    Directory of Open Access Journals (Sweden)

    Mariano Bizzarri

    2014-01-01

    Full Text Available The somatic mutation theory of carcinogenesis has eventually accumulated an impressive body of shortfalls and paradoxes, as admittedly claimed by its own supporters given that the cell-based approach can hardly explain the emergence of tissue-based processes, like cancer. However, experimental data and alternatives theories developed during the last decades may actually provide a new framework on which cancer research should be reframed. Such issue may be fulfilled embracing new theoretical perspectives, taking the cells-microenvironment interplay as the privileged level of observation and assuming radically different premises as well as new methodological frameworks. Within that perspective, the tumor microenvironment cannot be merely considered akin to new “factor” to be added to an already long list of “signaling factors”; microenvironment represents the physical-biochemical support of the morphogenetic field which drives epithelial cells towards differentiation and phenotype transformation, according to rules understandable only by means of a systems biology approach. That endeavour entails three fundamental aspects: general biological premises, the level of observation (i.e., the systems to which we are looking for, and the principles of biological organization that would help in integrating and understanding experimental data.

  11. Folate, vitamin B6, vitamin B12, and vitamin B2 intake, genetic polymorphisms of related enzymes, and risk of colorectal cancer in a hospital-based case-control study in Japan.

    Science.gov (United States)

    Otani, Tetsuya; Iwasaki, Motoki; Hanaoka, Tomoyuki; Kobayashi, Minatsu; Ishihara, Junko; Natsukawa, Syusuke; Shaura, Kozo; Koizumi, Yoichi; Kasuga, Yoshio; Yoshimura, Kimio; Yoshida, Teruhiko; Tsugane, Shoichiro

    2005-01-01

    We conducted a case-control study to investigate the association of nutrient intake involved in the one-carbon pathway of folate for DNA methylation and DNA synthesis and the related enzyme genetic polymorphisms with colorectal cancer. Cases were 107 patients newly diagnosed with colorectal cancer. Controls were 224 subjects matched with cases by sex, age, and residential area. Nutrient intake was assessed by a self-administered, semiquantitative food-frequency questionnaire. Four genetic polymorphisms-MTHFR C677T and A1298C, MTRR A66G, and ALDH2 Glu487Lys-were determined using blood samples. Odds ratios were calculated using conditional logistic regression analysis adjusted for smoking, alcohol consumption, body mass index, and dietary fiber intake. Although folate intake was inversely associated with colorectal cancer, this association was attenuated after further controlling for dietary fiber intake. Neither vitamin B6, vitamin B12, nor vitamin B2, nor any genetic polymorphism was significantly associated with colorectal cancer. MTRR polymorphism interacted with the association of folate (P for interaction = 0.04) or vitamin (P for interaction = 0.02) with colorectal cancer, although the other polymorphisms did not interact with any nutrient intake. In conclusion, the study did not support the existing hypothesis of gene-nutrient interaction in colorectal carcinogenesis.

  12. Modifiable risk factors and colorectal adenomas among those at high risk of colorectal cancer

    NARCIS (Netherlands)

    Botma, A.

    2011-01-01

    Epidemiological studies have identified several modifiable risk factors for colorectal neoplasms in the general population. However, associations between modifiable risk factors, including body mass index (BMI), smoking, alcohol consumption and dietary patterns, and colorectal neoplasms in two

  13. A Review of the Role of Neurotensin and Its Receptors in Colorectal Cancer

    Directory of Open Access Journals (Sweden)

    Shengyang Qiu

    2017-01-01

    Full Text Available Neurotensin (NTS is a physiologically occurring hormone which affects the function of the gastrointestinal (GI tract. In recent years, NTS, acting through its cellular receptors (NTSR, has been implicated in the carcinogenesis of several cancers. In colorectal cancer (CRC, a significant body of evidence, from in vitro and in vivo studies, is available which elucidates the molecular biology of NTS/NTSR signalling and the resultant growth of CRC cells. There is growing clinical data from human studies which corroborate the role NTS/NTSR plays in the development of human CRC. Furthermore, blockade and modulation of the NTS/NTSR signalling pathways appears to reduce CRC growth in cell cultures and animal studies. Lastly, NTS/NTSR also shows potential of being utilised as a diagnostic biomarker for cancers as well as targets for functional imaging. We summarise the existing evidence and understanding of the role of NTS and its receptors in CRC.

  14. Gene-gene and gene-environment interactions in prostate, breast and colorectal cancer

    DEFF Research Database (Denmark)

    Kopp, Tine Iskov

    as having strong influence on carcinogenesis. Therefore, very frequent, low effect polymorphisms may have a greater contribution on a population level in combination with environmental factors. Indeed, several dietary and life style factors are now well-established risk factors for different cancer types...... preparation methods or the life style associated with high red meat intake is carcinogenic. The acquired knowledge would improve the current dietary recommendations. There also seem to be several yet unknown effects of NSAID usage that need to be clarified. Information of these potential (side) effects would......The incidence of cancer in the western world has increased steeply during the last 50 years. For three of the most prevalent cancer types in Denmark, prostate, breast and colorectal cancer (PC, BC and CRC, respectively), only a small fraction (1-15%) of the incidences are caused by highly penetrant...

  15. Heme oxygenase-1 polymorphism is not associated with risk of colorectal cancer: a Danish prospective study

    DEFF Research Database (Denmark)

    Vogel, Ulla Birgitte; Andersen, Vibeke; Christensen, Jane

    2011-01-01

    Objective: Intake of red and processed meat confers risk of colorectal cancer (CRC). We wanted to test whether heme in meat promotes carcinogenesis. Methods: Heme oxygenase-1 (HO-1, HMOX1) A-413T (rs2071746) was assessed in a nested case–cohort study of 383 CRC cases and 763 randomly selected...... participants from a prospective study of 57 053 individuals. Incidence rate ratios and 95% confidence intervals were calculated. Results: No association was found between the HO-1 polymorphism and CRC (P value for trend for the fully adjusted estimates=0.29). No interaction with meat intake was found (P value...... for interaction=0.55). Conclusion: The studied HO-1 polymorphism was not associated with risk of CRC suggesting that heme from meat is not important in CRC development....

  16. Effects of Progressive Muscle Relaxation Therapy in Colorectal Cancer Patients.

    Science.gov (United States)

    Kim, Kyeng Jin; Na, Yeon Kyung; Hong, Hae Sook

    2016-08-01

    This study aimed to examine the effect of progressive muscle relaxation therapy (PMRT) on cortisol level, the Stress Arousal Checklist (SACL) score, blood pressure, and heart rate in colorectal cancer patients undergoing laparoscopic surgery. Forty-six patients were divided into control and experimental groups. Cortisol levels, blood pressure, and heart rate were measured before surgery and between 8:00 and 11:00 a.m. on the first, third, and fifth days after surgery. SACL score was measured before surgery and on the fifth day after surgery at the same time points. PMRT was performed twice a day for 5 days. Analyses of covariance with advanced covariate levels and t tests showed that PMRT helps colorectal cancer patients achieve a lower stress response and provides an important basis for stress control. © The Author(s) 2016.

  17. Translesion Synthesis Polymerases in the Prevention and Promotion of Carcinogenesis

    Directory of Open Access Journals (Sweden)

    L. Jay Stallons

    2010-01-01

    Full Text Available A critical step in the transformation of cells to the malignant state of cancer is the induction of mutations in the DNA of cells damaged by genotoxic agents. Translesion DNA synthesis (TLS is the process by which cells copy DNA containing unrepaired damage that blocks progression of the replication fork. The DNA polymerases that catalyze TLS in mammals have been the topic of intense investigation over the last decade. DNA polymerase η (Pol η is best understood and is active in error-free bypass of UV-induced DNA damage. The other TLS polymerases (Pol ι, Pol κ, REV1, and Pol ζ have been studied extensively in vitro, but their in vivo role is only now being investigated using knockout mouse models of carcinogenesis. This paper will focus on the studies of mice and humans with altered expression of TLS polymerases and the effects on cancer induced by environmental agents.

  18. Mucin-Type O-Glycosylation in Gastric Carcinogenesis

    Directory of Open Access Journals (Sweden)

    Henrique O. Duarte

    2016-07-01

    Full Text Available Mucin-type O-glycosylation plays a crucial role in several physiological and pathological processes of the gastric tissue. Modifications in enzymes responsible for key glycosylation steps and the consequent abnormal biosynthesis and expression of their glycan products constitute well-established molecular hallmarks of disease state. This review addresses the major role played by mucins and associated O-glycan structures in Helicobacter pylori adhesion to the gastric mucosa and the subsequent establishment of a chronic infection, with concomitant drastic alterations of the gastric epithelium glycophenotype. Furthermore, alterations of mucin expression pattern and glycan signatures occurring in preneoplastic lesions and in gastric carcinoma are also described, as well as their impact throughout the gastric carcinogenesis cascade and in cancer progression. Altogether, mucin-type O-glycosylation alterations may represent promising biomarkers with potential screening and prognostic applications, as well as predictors of cancer patients’ response to therapy.

  19. Carcinogenesis related to intense pulsed light and UV exposure

    DEFF Research Database (Denmark)

    Hedelund, L; Lerche, C; Wulf, H C

    2006-01-01

    This study examines whether intense pulsed light (IPL) treatment has a carcinogenic potential itself or may influence ultraviolet (UV)-induced carcinogenesis. Secondly, it evaluates whether UV exposure may influence IPL-induced side effects. Hairless, lightly pigmented mice (n=144) received three...... observation period. Side effects were evaluated clinically. No tumors appeared in untreated control mice or in just IPL-treated mice. Skin tumors developed in UV-exposed mice independently of IPL treatments. The time it took for 50% of the mice to first develop skin tumor ranged from 47 to 49 weeks...... in preoperative UV-exposed mice (p=0.94) and from 22 to 23 weeks in pre- and postoperative UV-exposed mice (p=0.11). IPL rejuvenation of lightly pigmented skin did not induce pigmentary changes (p=1.00). IPL rejuvenation of UV-pigmented skin resulted in an immediate increased skin pigmentation and a subsequent...

  20. NADPH Oxidases and Their Roles in Skin Homeostasis and Carcinogenesis.

    Science.gov (United States)

    Rudolf, Jana; Raad, Houssam; Taieb, Alain; Rezvani, Hamid Reza

    2017-11-17

    Skin protects the body from dehydration, pathogens, and external mutagens. NADPH oxidases are central components for regulating the cellular redox balance. There is increasing evidence indicating that reactive oxygen species (ROS) generated by members of this enzyme family play important roles in the physiology and pathophysiology of the skin. Recent Advances: NADPH oxidases are active producers of ROS such as superoxide and hydrogen peroxide. Different isoforms are found in virtually all tissues. They play pivotal roles in normal cell homeostasis and in the cellular responses to various stressors. In particular, these enzymes are integral parts of redox-sensitive prosurvival and proapoptotic signaling pathways, in which they act both as effectors and as modulators. However, continuous (re)activation of NADPH oxidases can disturb the redox balance of cells, in the worst-case scenario in a permanent manner. Abnormal NADPH oxidase activity has been associated with a wide spectrum of diseases, as well as with aging and carcinogenesis. Sunlight with its beneficial and deleterious effects induces the activation of NADPH oxidases in the skin. Evidence for the important roles of this enzyme family in skin cancer and skin aging, as well as in many chronic skin diseases, is now emerging. Understanding the precise roles of NADPH oxidases in normal skin homeostasis, in the cellular responses to solar radiation, and during carcinogenesis will pave the way for their validation as therapeutic targets not only for the prevention and treatment of skin cancers but also for many other skin-related disorders. Antioxid. Redox Signal. 00, 000-000.

  1. Mushroom Ganoderma lucidum prevents colitis-associated carcinogenesis in mice.

    Directory of Open Access Journals (Sweden)

    Daniel Sliva

    Full Text Available Epidemiological studies suggest that mushroom intake is inversely correlated with gastric, gastrointestinal and breast cancers. We have recently demonstrated anticancer and anti-inflammatory activity of triterpene extract isolated from mushroom Ganoderma lucidum (GLT. The aim of the present study was to evaluate whether GLT prevents colitis-associated carcinogenesis in mice.Colon carcinogenesis was induced by the food-borne carcinogen (2-Amino-1-methyl-6-phenylimidazol[4,5-b]pyridine [PhIP] and inflammation (dextran sodium sulfate [DSS] in mice. Mice were treated with 0, 100, 300 and 500 mg GLT/kg of body weight 3 times per week for 4 months. Cell proliferation, expression of cyclin D1 and COX-2 and macrophage infiltration was assessed by immunohistochemistry. The effect of GLT on XRE/AhR, PXR and rPXR was evaluated by the reporter gene assays. Expression of metabolizing enzymes CYP1A2, CYP3A1 and CYP3A4 in colon tissue was determined by immunohistochemistry. GLT treatment significantly suppressed focal hyperplasia, aberrant crypt foci (ACF formation and tumor formation in mice exposed to PhIP/DSS. The anti-proliferative effects of GLT were further confirmed by the decreased staining with Ki-67 in colon tissues. PhIP/DSS-induced colon inflammation was demonstrated by the significant shortening of the large intestine and macrophage infiltrations, whereas GLT treatment prevented the shortening of colon lengths, and reduced infiltration of macrophages in colon tissue. GLT treatment also significantly down-regulated PhIP/DSS-dependent expression of cyclin D1, COX-2, CYP1A2 and CYP3A4 in colon tissue.Our data suggest that GLT could be considered as an alternative dietary approach for the prevention of colitis-associated cancer.

  2. Role of detection of microsatellite instability in Chinese with hereditary nonpolyposis colorectal cancer or ordinary hereditary colorectal cancer

    OpenAIRE

    Liu, Wen-Zhi; Jin, Feng; ZHANG, ZHEN-HAI; Wang, Shu-Bao

    2006-01-01

    AIM: To detect microsatellite instability (MSI) in patients with hereditary nonpolyposis colorectal cancer or ordinary hereditary colorectal cancer and to provide criteria for screening the kindreds with hereditary nonpolyposis colorectal cancer at molecular level.

  3. Colorectal cancer through simulation and experiment

    KAUST Repository

    Kershaw, Sophie K.

    2013-06-01

    Colorectal cancer (CRC) has formed a canonical example of tumourigenesis ever since its use in Fearon and Vogelstein\\'s linear model of genetic mutation, and continues to generate a huge amount of research interest. Over time, the field has witnessed a transition from solely experimental work to the inclusion of mathematical and computational modelling. The fusion of these disciplines has the potential to provide valuable insights into oncologic processes, but also presents the challenge of uniting many diverse perspectives. Furthermore, the cancer cell phenotype defined by the \\'Hallmarks of Cancer\\' has been extended in recent times and provides an excellent basis for future research. The authors present a timely summary of the literature relating to CRC, addressing the traditional experimental findings, summarising the key mathematical and computational approaches, and emphasising the role of the Hallmarks in current and future developments. The authors conclude with a discussion of interdisciplinary work, outlining areas of experimental interest which would benefit from the insight that theoretical modelling can provide. © The institution of engineering and technology 2013.

  4. Aging related methylation influences the gene expression of key control genes in colorectal cancer and adenoma.

    Science.gov (United States)

    Galamb, Orsolya; Kalmár, Alexandra; Barták, Barbara Kinga; Patai, Árpád V; Leiszter, Katalin; Péterfia, Bálint; Wichmann, Barnabás; Valcz, Gábor; Veres, Gábor; Tulassay, Zsolt; Molnár, Béla

    2016-12-21

    To analyze colorectal carcinogenesis and age-related DNA methylation alterations of gene sequences associated with epigenetic clock CpG sites. In silico DNA methylation analysis of 353 epigenetic clock CpG sites published by Steve Horvath was performed using methylation array data for a set of 123 colonic tissue samples [64 colorectal cancer (CRC), 42 adenoma, 17 normal; GEO accession number: GSE48684]. Among the differentially methylated age-related genes, secreted frizzled related protein 1 (SFRP1) promoter methylation was further investigated in colonic tissue from 8 healthy adults, 19 normal children, 20 adenoma and 8 CRC patients using bisulfite-specific PCR followed by methylation-specific high resolution melting (MS-HRM) analysis. mRNA expression of age-related "epigenetic clock" genes was studied using Affymetrix HGU133 Plus2.0 whole transcriptome data of 153 colonic biopsy samples (49 healthy adult, 49 adenoma, 49 CRC, 6 healthy children) (GEO accession numbers: GSE37364, GSE10714, GSE4183, GSE37267). Whole promoter methylation analysis of genes showing inverse DNA methylation-gene expression data was performed on 30 colonic samples using methyl capture sequencing. Fifty-seven age-related CpG sites including hypermethylated PPP1R16B, SFRP1, SYNE1 and hypomethylated MGP, PIPOX were differentially methylated between CRC and normal tissues (P genes were changed, while in adenoma samples 102 genes showed differential expression compared with normal colonic tissue (P 0.5). The change of expression for several genes including SYNE1, CLEC3B, LTBP3 and SFRP1, followed the same pattern in aging and carcinogenesis, though not for all genes (e.g., MGP). Several age-related DNA methylation alterations can be observed during CRC development and progression affecting the mRNA expression of certain CRC- and adenoma-related key control genes.

  5. Microbial and viral pathogens in colorectal cancer.

    LENUS (Irish Health Repository)

    Collins, Danielle

    2012-02-01

    The heterogenetic and sporadic nature of colorectal cancer has led to many epidemiological associations with causes of this disease. As our understanding of the underlying molecular processes in colorectal-cancer develops, the concept of microbial-epithelial interactions as an oncogenic trigger might provide a plausible hypothesis for the pathogenesis of colorectal cancer. By contrast with other cancers of the gastrointestinal tract (gastric carcinoma, mucosa-associated lymphoid-tissue lymphoma), a direct causal link between microbial infection (bacteria and viruses) and colorectal carcinoma has not been established. Studies support the involvement of these organisms in oncogenesis, however, in colorectal cancer, clinical data are lacking. Here, we discuss current evidence (both in vitro and clinical studies), and focus on a putative role for bacterial and viral pathogens as a cause of colorectal cancer.

  6. Microbial and viral pathogens in colorectal cancer.

    LENUS (Irish Health Repository)

    Collins, Danielle

    2011-05-01

    The heterogenetic and sporadic nature of colorectal cancer has led to many epidemiological associations with causes of this disease. As our understanding of the underlying molecular processes in colorectal-cancer develops, the concept of microbial-epithelial interactions as an oncogenic trigger might provide a plausible hypothesis for the pathogenesis of colorectal cancer. By contrast with other cancers of the gastrointestinal tract (gastric carcinoma, mucosa-associated lymphoid-tissue lymphoma), a direct causal link between microbial infection (bacteria and viruses) and colorectal carcinoma has not been established. Studies support the involvement of these organisms in oncogenesis, however, in colorectal cancer, clinical data are lacking. Here, we discuss current evidence (both in vitro and clinical studies), and focus on a putative role for bacterial and viral pathogens as a cause of colorectal cancer.

  7. Dietary patterns during high school and risk of colorectal adenoma in a cohort of middle-aged women.

    Science.gov (United States)

    Nimptsch, Katharina; Malik, Vasanti S; Fung, Teresa T; Pischon, Tobias; Hu, Frank B; Willett, Walter C; Fuchs, Charles S; Ogino, Shuji; Chan, Andrew T; Giovannucci, Edward; Wu, Kana

    2014-05-15

    Adolescent diet may be etiologically relevant for later risk of colorectal adenoma, a precursor of colorectal cancer. We aimed to examine associations between adolescent dietary patterns (derived using factor analysis) and risk of colorectal adenoma in middle adulthood. We analyzed data from 17,221 women participating in the Nurses' Health Study II, who had completed a validated high school (HS) food frequency questionnaire in 1998 when they were 34-51 years old, and had subsequently undergone at least one lower bowel endoscopy. Between 1998 and 2007, 1,299 women were diagnosed with at least one colorectal adenoma. In multivariable models adjusted for adult dietary patterns, a higher "prudent" pattern during HS, characterized by high consumption of vegetables, fruit and fish was associated with a statistically significantly lower risk of rectal (odds ratio [OR] highest vs. lowest quintile, 0.45, 95% CI 0.27-0.75, p-trend = 0.005), but not colon adenomas. A higher "Western" pattern during HS, characterized by high consumption of desserts and sweets, snack foods and red and processed meat, was significantly associated with rectal (OR 1.78, 95% CI 1.12-2.85, p-trend = 0.005) and advanced (OR 1.58, 95% CI 1.07-2.33, p-trend = 0.08), but not associated with colon or non-advanced adenomas. This study suggests that overall eating patterns during high school may influence later risk of rectal and advanced adenoma, independent of adult diet. Our results support the hypothesis that diet during early life may influence colorectal carcinogenesis. © 2013 UICC.

  8. Evaluation of 1p Losses in Primary Carcinomas, Local Recurrences and Peripheral Metastases from Colorectal Cancer Patients

    Directory of Open Access Journals (Sweden)

    Lin Thorstensen

    2000-01-01

    Full Text Available Cytogenetic and molecular genetic analyses of colorectal adenomas and carcinomas have shown that loss of the distal part of chromosome arm 1p is common, particularly in tumors of the left colon. Because the importance of 1p loss in colorectal cancer metastases is unknown, we compared the frequency, exact site and extent of ip deletions in primary carcinomas (n=28, local recurrences (n=19 and metastases (n=33 from 67 colorectal cancer patients using 14 markers in an allelic imbalance study. Loss of 1p was found in 50% of the primary carcinomas, 33% of the local recurrences, and 64% of the metastases, revealing a significant difference between the local recurrences and the metastases (P=.04. The smallest region of 1p deletion overlap (SRO defined separately for each group of lesions had the region between markers Di S2647 and D1 S2644, at 1 p35-36, in common. The genes PLA2G2A (1p35.1-36 and TP73 (1p36.3 were shown to lie outside this consistently lost region, suggesting that neither of them are targets for the 1p loss. In the second part of the study, microdissected primary carcinomas and distant metastases from the same colorectal cancer patients (n=18 were analyzed, and the same 1p genotype was found in the majority of patients (12/18, 67%. The finding that primary carcinoma cells with metastatic ability usually contain 1p deletions, and that some cases lacking 1p alterations in the primary tumor acquire such changes during growth of a metastatic lesion, supports the notion that 1p loss may be important both early and late in colorectal carcinogenesis, with the apparent exception of local recurrences.

  9. Novel understanding of ABC transporters ABCB1/MDR/P-glycoprotein, ABCC2/MRP2, and ABCG2/BCRP in colorectal pathophysiology

    DEFF Research Database (Denmark)

    Andersen, Vibeke; Svenningsen, Katrine; Knudsen, Lina Almind

    2015-01-01

    transporter proteins, inflammatory bowel disease, ulcerative, colitis, Crohns disease, colorectal cancer, colitis, intestinal inflammation, intestinal carcinogenesis, ABCB1/P-glycoprotein (P-gp/CD243/MDR1), ABCC2/multidrug resistance protein 2 (MRP2) and ABCG2/breast cancer resistance protein (BCRP), Abcb1....../Mdr1a, abcc2/Mrp2, abcg2/Bcrp, knock-out mice, tight junction, membrane lipid function. RESULTS: Recently, human studies reported that changes in the levels of ABC transporters were early events in the adenoma-carcinoma sequence leading to CRC. A link between ABCB1, high fat diet and gut microbes...

  10. Common cancer in a wild animal: the California sea lion (Zalophus californianus) as an emerging model for carcinogenesis.

    Science.gov (United States)

    Browning, Helen M; Gulland, Frances M D; Hammond, John A; Colegrove, Kathleen M; Hall, Ailsa J

    2015-07-19

    Naturally occurring cancers in non-laboratory species have great potential in helping to decipher the often complex causes of neoplasia. Wild animal models could add substantially to our understanding of carcinogenesis, particularly of genetic and environmental interactions, but they are currently underutilized. Studying neoplasia in wild animals is difficult and especially challenging in marine mammals owing to their inaccessibility, lack of exposure history, and ethical, logistical and legal limits on experimentation. Despite this, California sea lions (Zalophus californianus) offer an opportunity to investigate risk factors for neoplasia development that have implications for terrestrial mammals and humans who share much of their environment and diet. A relatively accessible California sea lion population on the west coast of the USA has a high prevalence of urogenital carcinoma and is regularly sampled during veterinary care in wildlife rehabilitation centres. Collaborative studies have revealed that genotype, persistent organic pollutants and a herpesvirus are all associated with this cancer. This paper reviews research to date on the epidemiology and pathogenesis of urogenital carcinoma in this species, and presents the California sea lion as an important and currently underexploited wild animal model of carcinogenesis. © 2015 The Author(s) Published by the Royal Society. All rights reserved.

  11. Microsatellite instability in colorectal cancer: clinicopathological significance

    National Research Council Canada - National Science Library

    Setaffy, Lisa; Langner, Cord

    2015-01-01

    Although often viewed as a single disease, colorectal cancer more accurately represents a constellation of heterogeneous subtypes that result from different combinations of genetic events and epigenetic alterations...

  12. Novel understanding of ABC transporters ABCB1/MDR/P-glycoprotein, ABCC2/MRP2, and ABCG2/BCRP in colorectal pathophysiology

    DEFF Research Database (Denmark)

    Andersen, Vibeke; Svenningsen, Katrine; Almind Knudsen, Lina

    2015-01-01

    AIM: To evaluate ATP-binding cassette (ABC) transporters in colonic pathophysiology as they had recently been related to colorectal cancer (CRC) development. METHODS: Literature search was conducted on PubMed using combinations of the following terms: ABC transporters, ATP binding cassette...... transporter proteins, inflammatory bowel disease, ulcerative, colitis, Crohns disease, colorectal cancer, colitis, intestinal inflammation, intestinal carcinogenesis, ABCB1/P-glycoprotein (P-gp/CD243/MDR1), ABCC2/multidrug resistance protein 2 (MRP2) and ABCG2/breast cancer resistance protein (BCRP), Abcb1...... pathogen-free Abcb1 KO mice. The Abcb1 KO mice might thus serve as a model in which diet/environmental factors and microbes may be controlled and investigated in relation to intestinal inflammation. Potential molecular mechanisms include defective transport of inflammatory mediators and/or phospholipid...

  13. Interaction between interleukin-10 (IL-10) polymorphisms and dietary fibre in relation to risk of colorectal cancer in a Danish case-cohort study

    DEFF Research Database (Denmark)

    Andersen, Vibeke; Egeberg, Rikke; Tjonneland, Anne

    2012-01-01

    Background: More than 50% of the colorectal cancer (CRC) etiology has been attributed to diet. Established or suspected dietary factors modifying risk of CRC are red meat, cereals, fish, and fibre. Diet and lifestyle may be linked to cancer through inflammation. Interleukin-10 (IL-10) is an anti......-inflammatory cytokine. We wanted to test if dietary factors and IL10 polymorphisms interact in relation to colorectal carcinogenesis. Methods: The functional IL10 polymorphism C-592A (rs1800872) and the marker rs3024505 were assessed in relation to diet and lifestyle in a nested case-cohort study of 378 CRC cases...... and 775 randomly selected participants from a prospective study of 57,053 persons. Genotyping data on the IL10 polymorphism C-592A, smoking and nonsteroidal anti-inflammatory drugs (NSAID) was retrieved from Vogel et al. (Mutat Res, 2007; 624: 88). Incidence rate ratios (IRR) and 95% Confidence Interval...

  14. Subnuclear proteomics in colorectal cancer

    DEFF Research Database (Denmark)

    Albrethsen, Jakob; Knol, Jaco C; Piersma, Sander R

    2010-01-01

    Abnormalities in nuclear phenotype and chromosome structure are key features of cancer cells. Investigation of the protein determinants of nuclear subfractions in cancer may yield molecular insights into aberrant chromosome function and chromatin organization and in addition may yield biomarkers...... for early cancer detection. Here we evaluate a proteomics work flow for profiling protein constituents in subnuclear domains in colorectal cancer tissues and apply this work flow to a comparative analysis of the nuclear matrix fraction in colorectal adenoma and carcinoma tissue samples. First, we...... established the reproducibility of the entire work flow. In a reproducibility analysis of three nuclear matrix fractions independently isolated from the same colon tumor homogenate, 889 of 1,047 proteins (85%) were reproducibly identified at high confidence (minimally two peptides per protein at 99...

  15. Diagnostic Ultrasound in Colorectal Cancer

    DEFF Research Database (Denmark)

    Rafaelsen, Søren Rafael

    2014-01-01

    tumour stage and whether there is distant spread of the disease at the time of diagnosis. Ultrasound Diagnostics is non-unionized and less costly than MDCT, MRI and PET/CT. Although MRI in recent years has gained ground in diagnostics in Denmark, there are still patients who have contraindications to MRI...... or are non-compliant. Also, patient movement during the MRI sequence acquisition degrades image quality on MRI and decreases accuracy. Over the last years, the ultrasound technique has improved further by Power Doppler, intravenous contrast enhancement, and elastography. Ultrasound diagnostics has...... the potential to contribute to the staging of colorectal cancer. The purpose of these studies was to determine the usefulness of ultrasound diagnostics in patients with colorectal cancer.The purpose of the TRUS studies was to compare staging of rectal carcinomas using digital rectal exploration...

  16. Colorectal cancers and chlorinated water

    OpenAIRE

    El-Tawil, Ahmed Mahmoud

    2016-01-01

    Published reports have revealed increased risk of colorectal cancers in people exposed to chlorinated drinking water or chemical derivatives of chlorination. Oestrogen plays a dual positive functions for diminishing the possibilities of such risk by reducing the entrance, and increasing the excretion, of these chemicals. In addition, there are supplementary measures that could be employed in order to reduce this risk further, such as boiling the drinking water, revising the standard concentra...

  17. Immunotherapy for metastatic colorectal cancer

    DEFF Research Database (Denmark)

    Ellebaek, Eva; Andersen, Mads Hald; Svane, Inge Marie

    2012-01-01

    Although no immunotherapeutic treatment is approved for colorectal cancer (CRC) patients, promising results from clinical trials suggest that several immunotherapeutic strategies may prove efficacious and applicable to this group of patients. This review describes the immunogenicity of CRC...... and presents the most interesting strategies investigated so far: cancer vaccination including antigen-defined vaccination and dendritic cell vaccination, chemo-immunotherapy, and adoptive cell transfer. Future treatment options as well as the possibility of combining existing therapies will be discussed along...

  18. Danish Colorectal Cancer Group Database.

    Science.gov (United States)

    Ingeholm, Peter; Gögenur, Ismail; Iversen, Lene H

    2016-01-01

    The aim of the database, which has existed for registration of all patients with colorectal cancer in Denmark since 2001, is to improve the prognosis for this patient group. All Danish patients with newly diagnosed colorectal cancer who are either diagnosed or treated in a surgical department of a public Danish hospital. The database comprises an array of surgical, radiological, oncological, and pathological variables. The surgeons record data such as diagnostics performed, including type and results of radiological examinations, lifestyle factors, comorbidity and performance, treatment including the surgical procedure, urgency of surgery, and intra- and postoperative complications within 30 days after surgery. The pathologists record data such as tumor type, number of lymph nodes and metastatic lymph nodes, surgical margin status, and other pathological risk factors. The database has had >95% completeness in including patients with colorectal adenocarcinoma with >54,000 patients registered so far with approximately one-third rectal cancers and two-third colon cancers and an overrepresentation of men among rectal cancer patients. The stage distribution has been more or less constant until 2014 with a tendency toward a lower rate of stage IV and higher rate of stage I after introduction of the national screening program in 2014. The 30-day mortality rate after elective surgery has been reduced from >7% in 2001-2003 to database is a national population-based clinical database with high patient and data completeness for the perioperative period. The resolution of data is high for description of the patient at the time of diagnosis, including comorbidities, and for characterizing diagnosis, surgical interventions, and short-term outcomes. The database does not have high-resolution oncological data and does not register recurrences after primary surgery. The Danish Colorectal Cancer Group provides high-quality data and has been documenting an increase in short- and long

  19. Red meat and colorectal cancer

    OpenAIRE

    Nuri Faruk Aykan

    2015-01-01

    Colorectal cancer (CRC) is the third most common cancer in men and the second in women worldwide. More than half of cases occur in more developed countries. The consumption of red meat (beef, pork, lamb, veal, mutton) is high in developed countries and accumulated evidence until today demonstrated a convincing association between the intake of red meat and especially processed meat and CRC risk. In this review, meta-analyses of prospective epidemiological studies addressed to this association...

  20. Colorectal cancer family history assessment.

    Science.gov (United States)

    Kelly, Patricia Paul

    2011-10-01

    This article describes family history assessment for colorectal cancer in three outpatient gastroenterology units and examines gastroenterology unit nurses' knowledge and attitudes about family history assessments. Eighty-eight colonoscopy records were surveyed, and 16 RNs were interviewed. The medical record documentation was surveyed using a researcher-developed tool to identify type of cancer, age at disease onset, family relationship, and number of family members with cancer. Gastroenterology unit nurses were interviewed to assess knowledge and attitudes about family history assessment regarding colorectal cancer. Findings indicate that limited family history documentation was present in the medical record and that important age-at-disease-onset information was missing in 95% of patients with a family history of colorectal cancer and in 85% of patients with a family history of Lynch syndrome-associated cancers. No documentation was found in any charts about the number of affected relatives within the same family. Inconsistencies in family history documentation within the same medical record were noted, and family history information was found in multiple chart forms. Gastroenterology nurses rated family history as very important but gave a lower rating to personal knowledge about and resources for family history assessment.

  1. Treatment of colorectal liver metastases

    Directory of Open Access Journals (Sweden)

    Ismaili Nabil

    2011-11-01

    Full Text Available Abstract Colorectal cancer (CRC is the third most common cancer in the word. Liver metastasis is the most common site of colorectal metastases. The prognosis of resectable colorectal liver metastases (CRLM was improved in the recent years with the consideration of chemotherapy and surgical resection as part of the multidisciplinary management of the disease; the current 5-year survival rates after resection of liver metastases are 25% to 40%. Resectable synchronous or metachronous liver metastases should be treated with perioperative chemotherapy based on three months of FOLFOX4 (5-fluorouracil [5FU], folinic acid [LV], and oxaliplatin chemotherapy before surgery and three months after surgery. In the case of primary surgery, pseudo-adjuvant chemotherapy for 6 months, based on 5FU/LV, FOLFOX4, XELOX (capecitabine and oxaliplatin or FOLFIRI (5FU/LV and irinotecan, should be indicated. In potentially resectable disease, primary chemotherapy based on more intensive regimens such as FOLFIRINOX (5FU/LV, irinotecan and oxaliplatin should be considered to enhance the chance of cure. The palliative chemotherapy based on FOLFIRI, or FOLFOX4/XELOX with or without targeted therapies, is the mainstay treatment of unresectable disease. This review would provide additional insight into the problem of optimal integration of chemotherapy and surgery in the management of CRLM.

  2. MALIGNANCY IN LARGE COLORECTAL LESIONS

    Directory of Open Access Journals (Sweden)

    Carlos Eduardo Oliveira dos SANTOS

    2014-09-01

    Full Text Available Context The size of colorectal lesions, besides a risk factor for malignancy, is a predictor for deeper invasion Objectives To evaluate the malignancy of colorectal lesions ≥20 mm. Methods Between 2007 and 2011, 76 neoplasms ≥20 mm in 70 patients were analyzed Results The mean age of the patients was 67.4 years, and 41 were women. Mean lesion size was 24.7 mm ± 6.2 mm (range: 20 to 50 mm. Half of the neoplasms were polypoid and the other half were non-polypoid. Forty-two (55.3% lesions were located in the left colon, and 34 in the right colon. There was a high prevalence of III L (39.5% and IV (53.9% pit patterns. There were 72 adenomas and 4 adenocarcinomas. Malignancy was observed in 5.3% of the lesions. Thirty-three lesions presented advanced histology (adenomas with high-grade dysplasia or early adenocarcinoma, with no difference in morphology and site. Only one lesion (1.3% invaded the submucosa. Lesions larger than 30 mm had advanced histology (P = 0.001. The primary treatment was endoscopic resection, and invasive carcinoma was referred to surgery. Recurrence rate was 10.6%. Conclusions Large colorectal neoplasms showed a low rate of malignancy. Endoscopic treatment is an effective therapy for these lesions.

  3. Multifaceted enrichment analysis of RNA-RNA crosstalk reveals cooperating micro-societies in human colorectal cancer.

    Science.gov (United States)

    Mazza, Tommaso; Mazzoccoli, Gianluigi; Fusilli, Caterina; Capocefalo, Daniele; Panza, Anna; Biagini, Tommaso; Castellana, Stefano; Gentile, Annamaria; De Cata, Angelo; Palumbo, Orazio; Stallone, Raffaella; Rubino, Rosa; Carella, Massimo; Piepoli, Ada

    2016-05-19

    Alterations in the balance of mRNA and microRNA (miRNA) expression profiles contribute to the onset and development of colorectal cancer. The regulatory functions of individual miRNA-gene pairs are widely acknowledged, but group effects are largely unexplored. We performed an integrative analysis of mRNA-miRNA and miRNA-miRNA interactions using high-throughput mRNA and miRNA expression profiles obtained from matched specimens of human colorectal cancer tissue and adjacent non-tumorous mucosa. This investigation resulted in a hypernetwork-based model, whose functional backbone was fulfilled by tight micro-societies of miRNAs. These proved to modulate several genes that are known to control a set of significantly enriched cancer-enhancer and cancer-protection biological processes, and that an array of upstream regulatory analyses demonstrated to be dependent on miR-145, a cell cycle and MAPK signaling cascade master regulator. In conclusion, we reveal miRNA-gene clusters and gene families with close functional relationships and highlight the role of miR-145 as potent upstream regulator of a complex RNA-RNA crosstalk, which mechanistically modulates several signaling pathways and regulatory circuits that when deranged are relevant to the changes occurring in colorectal carcinogenesis. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

  4. The Role of Chromosomal Instability and Epigenetics in Colorectal Cancers Lacking β-Catenin/TCF Regulated Transcription

    Directory of Open Access Journals (Sweden)

    Wael M. Abdel-Rahman

    2016-01-01

    Full Text Available All colorectal cancer cell lines except RKO displayed active β-catenin/TCF regulated transcription. This feature of RKO was noted in familial colon cancers; hence our aim was to dissect its carcinogenic mechanism. MFISH and CGH revealed distinct instability of chromosome structure in RKO. Gene expression microarray of RKO versus 7 colon cancer lines (with active Wnt signaling and 3 normal specimens revealed 611 differentially expressed genes. The majority of the tested gene loci were susceptible to LOH in primary tumors with various β-catenin localizations as a surrogate marker for β-catenin activation. The immunohistochemistry of selected genes (IFI16, RGS4, MCTP1, DGKI, OBCAM/OPCML, and GLIPR1 confirmed that they were differentially expressed in clinical specimens. Since epigenetic mechanisms can contribute to expression changes, selected target genes were evaluated for promoter methylation in patient specimens from sporadic and hereditary colorectal cancers. CMTM3, DGKI, and OPCML were frequently hypermethylated in both groups, whereas KLK10, EPCAM, and DLC1 displayed subgroup specificity. The overall fraction of hypermethylated genes was higher in tumors with membranous β-catenin. We identified novel genes in colorectal carcinogenesis that might be useful in personalized tumor profiling. Tumors with inactive Wnt signaling are a heterogeneous group displaying interaction of chromosomal instability, Wnt signaling, and epigenetics.

  5. Effect of dietary supplementation on the prognostic value of urinary and serum 8-isoprostaglandin F2α in chemically-induced mammary carcinogenesis in the rat

    Directory of Open Access Journals (Sweden)

    Białek Sławomir

    2011-03-01

    Full Text Available Abstract Backround The aim of the present study was to assess the effects of zinc or copper and polyphenolic compounds on the 8-isoprostaglandin F2α concentration in the serum and urine of rats with mammary cancer (adenocarcinoma induced with 7,12-dimethylbenz[a]antracene. The research focused on the kinetics of alterations in urinary 8-isoPGF2α at the early stage of carcinogenesis as well as the influence of dietary factors on the process. The impact of selected compounds on the intensity of DMBA - induced carcinogenesis was also assessed. Result and conclusions Administration of DMBA, a compound that inducers mammary tumors in experimental animals, increased the serum and urinary 8-isoPGF2α levels in study rats. In the rat model, diet supplementation with zinc, combined with selected polyphenolic compounds (resveratrol or genistein yielded a statistically significant decrease in the rat serum and urinary biomarker concentration with a simultaneously significant stimulation of carcinogenesis. The results indicate that there is an inverse correlation between the intensity of DMBA-induced carcinogenicity and the level of 8-isoPGF2α in urine and serum of rats.

  6. Effect of luteolin on the levels of glycoproteins during azoxymethane-induced colon carcinogenesis in mice.

    Science.gov (United States)

    Pandurangan, Ashok Kumar; Dharmalingam, Prakash; Ananda Sadagopan, Suresh Kumar; Ganapasam, Sudhandiran

    2012-01-01

    Luteolin (LUT), a bioflavonoid has been used as a chemopreventive agent world-wide against chemically induced cancer. Hence we designed an experiment to assess chemopreventive action of LUT on lipid peroxidation (LPO) and glycoconjugates in azoxymethane (AOM)-induced colon carcinogenesis. Colon cancer was induced by 15 mg/body kg. body weight of AOM and administration of LUT (at the dose of 1.2 mg/kg. body weight) was till end of the study. Analysis of lipid peroxidative end products such as protein carbonyl (PC), malonadehyde (MDA) and conjucated dienes (CD) demonstrated significant increase in in AOM-induced animals with reduction by LUT (pmucoprotein were analyzed in serum and colon tissues examined histopathologically by periodic acid Schiff's (PAS) staining were also reversed by LUT l(p<0.05) . The secondary marker of colon cancer mucin depleted foci (MDF) was assessed in control and experimental group of animals. A characteristic increase of MDF was observed in AOM- induced colon cancer animals. Treatment with LUT decreased the incidence of MDF. These results suggest that LUT alters the expression of glycoconjugates and suppress colon cancer. Hence, we speculate that LUT can be used as a chemopreventive agent to treat colon cancer.

  7. Role of infectious agents in the carcinogenesis of brain and head and neck cancers

    Directory of Open Access Journals (Sweden)

    Alibek Kenneth

    2013-02-01

    Full Text Available Abstract This review concentrates on tumours that are anatomically localised in head and neck regions. Brain cancers and head and neck cancers together account for more than 873,000 cases annually worldwide, with an increasing incidence each year. With poor survival rates at late stages, brain and head and neck cancers represent serious conditions. Carcinogenesis is a multi-step process and the role of infectious agents in this progression has not been fully identified. A major problem with such research is that the role of many infectious agents may be underestimated due to the lack of or inconsistency in experimental data obtained globally. In the case of brain cancer, no infection has been accepted as directly oncogenic, although a number of viruses and parasites are associated with the malignancy. Our analysis of the literature showed the presence of human cytomegalovirus (HCMV in distinct types of brain tumour, namely glioblastoma multiforme (GBM and medulloblastoma. In particular, there are reports of viral protein in up to 100% of GBM specimens. Several epidemiological studies reported associations of brain cancer and toxoplasmosis seropositivity. In head and neck cancers, there is a distinct correlation between Epstein-Barr virus (EBV and nasopharyngeal carcinoma (NPC. Considering that almost every undifferentiated NPC is EBV-positive, virus titer levels can be measured to screen high-risk populations. In addition there is an apparent association between human papilloma virus (HPV and head and neck squamous cell carcinoma (HNSCC; specifically, 26% of HNSCCs are positive for HPV. HPV type 16 was the most common type detected in HNSCCs (90% and its dominance is even greater than that reported in cervical carcinoma. Although there are many studies showing an association of infectious agents with cancer, with various levels of involvement and either a direct or indirect causative effect, there is a scarcity of articles covering the role of

  8. Tucatinib (ONT-380) and Trastuzumab in Treating Patients With HER2+ Metastatic Colorectal Cancer

    Science.gov (United States)

    2018-02-08

    Colorectal Adenocarcinoma; ERBB2 Gene Amplification; HER2/Neu Positive; KRAS wt Allele; NRAS wt Allele; Recurrent Colorectal Carcinoma; Stage III Colorectal Cancer AJCC v7; Stage IIIA Colorectal Cancer AJCC v7; Stage IIIB Colorectal Cancer AJCC v7; Stage IIIC Colorectal Cancer AJCC v7; Stage IV Colorectal Cancer AJCC v7; Stage IVA Colorectal Cancer AJCC v7; Stage IVB Colorectal Cancer AJCC v7

  9. Effects of environmental stressors on histone modifications and their relevance to carcinogenesis: a systematic review.

    NARCIS (Netherlands)

    Dik, S.; Scheepers, P.T.J.; Godderis, L.

    2012-01-01

    Carcinogenesis is a complex process involving both genetic and epigenetic mechanisms. The cellular molecular epigenetic machinery, including histone modifications, is associated with changes in gene expression induced by exposure to environmental agents. In this paper, we systematically reviewed

  10. Investigating the Role of FIP200 in Mammary Carcinogenesis Using a Transgenic Mouse Model

    National Research Council Canada - National Science Library

    Nagy, Tamas

    2007-01-01

    ...) deletion in mammary-specific polyoma middle-T transgenic mice. We monitored mammary carcinogenesis in positive control (FAKFlox/Flox; MMTV-PyVT) and target (FAKFlox/Flox; MMTV-Cre; MMTV-PyVT) females...

  11. The role of type of tobacco and type of alcoholic beverage in oral carcinogenesis

    National Research Council Canada - National Science Library

    Castellsagué, Xavier; Quintana, Maria Jesús; Martínez, Maria Carmen; Nieto, Adoración; Sánchez, Maria José; Juan, Amparo; Monner, Antoni; Carrera, Marta; Agudo, Antoni; Quer, Miquel; Muñoz, Nubia; Herrero, Rolando; Franceschi, Silvia; Bosch, F. Xavier

    2004-01-01

    .... Spain has a population heavily exposed to various types of tobacco and alcoholic beverages but the role and impact of tobacco type and beverage type in oral carcinogenesis remain controversial...

  12. Downregulated Ku70 and ATM associated to poor prognosis in colorectal cancer among Chinese patients

    Directory of Open Access Journals (Sweden)

    Lu YF

    2014-10-01

    Full Text Available Yuanfang Lu,1,2 Jingyan Gao,1,3 Yuanming Lu,1 1Department of Toxicology, School of Public Health, Guilin Medical University, Guangxi, People's Republic of China; 2Department of Clinical Research Center, Affiliated 2nd Hospital of Nanjing Medical University, Nanjing, People's Republic of China; 3Department of Human Anatomy and Histo-Embryology, Shanghai Medical College, Fudan University, Shanghai, People's Republic of China Background: Double-strand DNA breaks (DSBs are a key factor in carcinogenesis. The necessary repair of DSBs is pivotal in maintaining normal cell division. To address the relationship between altered expression of DSB repair of proteins Ku70 and ataxia-telangiectasia mutated (ATM in colorectal cancer (CRC, we examined the expression levels and patterns of Ku70 and ATM in CRC samples. Methods: Expression and coexpression of Ku70 and ATM were investigated by using real-time quantitative polymerase chain reaction assays and confirmed further with fluorescent immunohistochemistry in CRC and pericancerous samples from 112 Chinese patients. Results: Downexpression patterns for both Ku70 and ATM were found in the CRC samples and were significantly associated with advanced tumor node metastasis stage and decreased 5-year overall survival rate. Conclusion: Downregulated Ku70 and ATM were associated with poor disease-free survival. Loss of Ku70 and ATM expression might act as a biomarker to predict poor prognosis in patients with CRC. Keywords: DNA double-strand breaks, ataxia-telangiectasia mutated, Ku70, colorectal cancer

  13. Building Up a Robust Risk Mathematical Platform to Predict Colorectal Cancer

    Directory of Open Access Journals (Sweden)

    Le Zhang

    2017-01-01

    Full Text Available Colorectal cancer (CRC, as a result of a multistep process and under multiple factors, is one of the most common life-threatening cancers worldwide. To identify the “high risk” populations is critical for early diagnosis and improvement of overall survival rate. Of the complicated genetic and environmental factors, which group is mostly concerning colorectal carcinogenesis remains contentious. For this reason, this study collects relatively complete information of genetic variations and environmental exposure for both CRC patients and cancer-free controls; a multimethod ensemble model for CRC-risk prediction is developed by employing such big data to train and test the model. Our results demonstrate that (1 the explored genetic and environmental biomarkers are validated to connect to the CRC by biological function- or population-based evidences, (2 the model can efficiently predict the risk of CRC after parameter optimization by the big CRC-related data, and (3 our innovated heterogeneous ensemble learning model (HELM and generalized kernel recursive maximum correntropy (GKRMC algorithm have high prediction power. Finally, we discuss why the HELM and GKRMC can outperform the classical regression algorithms and related subjects for future study.

  14. Potential of probiotics, prebiotics and synbiotics for management of colorectal cancer.

    Science.gov (United States)

    Raman, Maya; Ambalam, Padma; Kondepudi, Kanthi Kiran; Pithva, Sheetal; Kothari, Charmy; Patel, Arti T; Purama, Ravi Kiran; Dave, J M; Vyas, B R M

    2013-01-01

    Colorectal Cancer (CRC) is the second leading cause of cancer-related mortality and is the fourth most common malignant neoplasm in USA. Escaping apoptosis and cell mutation are the prime hallmarks of cancer. It is apparent that balancing the network between DNA damage and DNA repair is critical in preventing carcinogenesis. One-third of cancers might be prevented by nutritious healthy diet, maintaining healthy weight and physical activity. In this review, an attempt is made to abridge the role of carcinogen in colorectal cancer establishment and prognosis, where special attention has been paid to food-borne mutagens and functional role of beneficial human gut microbiome in evading cancer. Further the significance of tailor-made prebiotics, probiotics and synbiotics in cancer management by bio-antimutagenic and desmutagenic activity has been elaborated. Probiotic bacteria are live microorganisms that, when administered in adequate amounts, confer a healthy benefit on the host. Prebiotics are a selectively fermentable non-digestible oligosaccharide or ingredient that brings specific changes, both in the composition and/or activity of the gastrointestinal microflora, conferring health benefits. Synbiotics are a combination of probiotic bacteria and the growth promoting prebiotic ingredients that purport "synergism."

  15. Candidate predisposing germline copy number variants in early onset colorectal cancer patients.

    Science.gov (United States)

    Brea-Fernandez, A J; Fernandez-Rozadilla, C; Alvarez-Barona, M; Azuara, D; Ginesta, M M; Clofent, J; de Castro, L; Gonzalez, D; Andreu, M; Bessa, X; Llor, X; Xicola, R; Jover, R; Castells, A; Castellvi-Bel, S; Capella, G; Carracedo, A; Ruiz-Ponte, C

    2017-05-01

    A great proportion of the heritability of colorectal cancer (CRC) still remains unexplained, and rare variants, as well as copy number changes, have been proposed as potential candidates to explain the so-called 'missing heritability'. We aimed to identify rare high-to-moderately penetrant copy number variants (CNVs) in patients suspected of having hereditary CRC due to an early onset. We have selected for genome-wide copy number analysis, 27 MMR-proficient early onset CRC patients (1% in the in-house control CNV database (n = 629 healthy controls). Copy number assignment was checked by duplex real-time quantitative PCR or multiplex ligation probe amplification. Somatic mutation analysis in candidate genes included: loss of heterozygosity studies, point mutation screening, and methylation status of the promoter. We have identified two rare germline deletions involving the AK3 and SLIT2 genes in two patients. The search for a second somatic mutational event in the corresponding CRC tumors showed loss of heterozygosity in AK3, and promoter hypermethylation in SLIT2. Both genes have been previously related to colorectal carcinogenesis. These findings suggest that AK3 and SLIT2 may be potential candidates involved in genetic susceptibility to CRC.

  16. Expression of the phosphorylated MEK5 protein is associated with TNM staging of colorectal cancer

    Directory of Open Access Journals (Sweden)

    Hu Bang

    2012-03-01

    Full Text Available Abstract Background Activation of MEK5 in many cancers is associated with carcinogenesis through aberrant cell proliferation. In this study, we determined the level of phosphorylated MEK5 (pMEK5 expression in human colorectal cancer (CRC tissues and correlated it with clinicopathologic data. Methods pMEK5 expression was examined by immunohistochemistry in a tissue microarray (TMA containing 335 clinicopathologic characterized CRC cases and 80 cases of nontumor colorectal tissues. pMEK5 expression of 19 cases of primary CRC lesions and paired with normal mucosa was examined by Western blotting. The relationship between pMEK5 expression in CRC and clinicopathologic parameters, and the association of pMEK5 expression with CRC survival were analyzed respectively. Results pMEK5 expression was significantly higher in CRC tissues (185 out of 335, 55.2% than in normal tissues (6 out of 80, 7.5%; P P = 0.001, lymph node metastasis (P P P P P = 0.002 and 5-year overall survival rate (P P = 0.139; OS: P = 0.071. Conclusions pMEK5 expression is correlated with the staging of CRC and its expression might be helpful to the TNM staging system of CRC.

  17. Challenging a dogma: co-mutations exist in MAPK pathway genes in colorectal cancer.

    Science.gov (United States)

    Grellety, Thomas; Gros, Audrey; Pedeutour, Florence; Merlio, Jean-Philippe; Duranton-Tanneur, Valerie; Italiano, Antoine; Soubeyran, Isabelle

    2016-10-01

    Sequencing of genes encoding mitogen-activated protein kinase (MAPK) pathway proteins in colorectal cancer (CRC) has established as dogma that of the genes in a pathway only a single one is ever mutated. We searched for cases with a mutation in more than one MAPK pathway gene (co-mutations). Tumor tissue samples of all patients presenting with CRC, and referred between 01/01/2008 and 01/06/2015 to three French cancer centers for determination of mutation status of RAS/RAF+/-PIK3CA, were retrospectively screened for co-mutations using Sanger sequencing or next-generation sequencing. We found that of 1791 colorectal patients with mutations in the MAPK pathway, 20 had a co-mutation, 8 of KRAS/NRAS, and some even with a third mutation. More than half of the mutations were in codons 12 and 13. We also found 3 cases with a co-mutation of NRAS/BRAF and 9 with a co-mutation of KRAS/BRAF. In 2 patients with a co-mutation of KRAS/NRAS, the co-mutation existed in the primary as well as in a metastasis, which suggests that co-mutations occur early during carcinogenesis and are maintained when a tumor disseminates. We conclude that co-mutations exist in the MAPK genes but with low frequency and as yet with unknown outcome implications.

  18. Crucial involvement of tumor-associated neutrophils in the regulation of chronic colitis-associated carcinogenesis in mice.

    Directory of Open Access Journals (Sweden)

    Kun Shang

    Full Text Available Ulcerative colitis (UC is a major form of chronic inflammation that can frequently progress to colon cancer. Several studies have demonstrated massive infiltration of neutrophils and macrophages into the lamina propria and submucosa in the progression of UC-associated colon carcinogenesis. Macrophages contribute to the development of colitis-associated colon cancer (CAC. However, the role of neutrophils is not well understood. To better understand the involvement of tumor-associated neutrophils (TANs in the regulation of CAC, we used a mouse CAC model produced by administering azoxymethane (AOM, followed by repeated dextran sulfate sodium (DSS ingestion. This causes severe colonic inflammation and subsequent development of multiple tumors in mice colon. We observed that colorectal mucosal inflammation became increasingly severe with AOM and DSS treatment. Macrophages infiltrated the lamina propria and submucosa, together with a marked increase in neutrophil infiltration. The chemokine CXCL2 increased in the lamina propria and submucosal regions of the colons of the treated mice, together with the infiltration of neutrophils expressing CXCR2, a specific receptor for CXCL2. This process was followed by neoplastic transformation. After AOM and DSS treatment, the mice showed enhanced production of metalloproteinase (MMP-9 and neutrophil elastase (NE, accompanied by excessive vessel generation and cell proliferation. Moreover, CXCL2 promoted neutrophil recruitment and induced neutrophils to express MMP-9 and NE in vitro. Furthermore, administration of neutrophil-neutralizing antibodies after the last DSS cycle markedly reduced the number and size of tumors and decreased the expression of CXCR2, CXCL2, MMP-9, and NE. These observations indicate a crucial role for TANs in the initiation and progression of CAC and suggest that the CXCL2-CXCR2 axis might be useful in reducing the risk of UC-associated colon cancer.

  19. Dietary chemoprevention of PhIP induced carcinogenesis in male Fischer 344 rats with tomato and broccoli.

    Directory of Open Access Journals (Sweden)

    Kirstie Canene-Adams

    Full Text Available The heterocyclic amine, 2-amino-1-methyl-6-phenylimidazo[4,5-B]pyridine (PhIP, found in meats cooked at high temperatures, has been implicated in epidemiological and rodent studies for causing breast, prostate, and colorectal cancers. A previous animal study using a xenograft model has shown that whole tomato and broccoli, when eaten in combination, exhibit a marked effect on tumor reduction compared to when eaten alone. Our aim was to determine if PhIP-induced carcinogenesis can be prevented by dietary consumption of whole tomato + broccoli powders. Male Fischer 344 rats (n = 45 were randomized into the following treatment groups: control (AIN93G diet, PhIP (200 ppm in AIN93G diet for the first 20 weeks of the study, or tomato + broccoli + PhIP (mixed in AIN93G diet at 10% each and fed with PhIP for 20 weeks, and then without PhIP for 32 weeks. Study animals were monitored for 52 weeks and were euthanized as necessary based on a set of criteria for health status and tumor burden. Although there appeared to be some hepatic and intestinal toxicity due to the combination of PhIP and tomato + broccoli, these rodents had improved survival and reduced incidence and/or severity of PhIP-induced neoplastic lesions compared to the PhIP-alone treated group. Rats eating tomato + broccoli exhibited a marked decrease in the number and size of cribiform prostatic intraepitheilial neoplasia/carcinoma in situ (cribiform PIN/CIS lesions and in the incidence of invasive intestinal adenocarcinomas and skin carcinomas. Although the apparent toxic effects of combined PhIP and tomato + broccoli need additional study, the results of this study support the hypothesis that a diet rich in tomato and broccoli can reduce or prevent dietary carcinogen-induced cancers.

  20. Dietary chemoprevention of PhIP induced carcinogenesis in male Fischer 344 rats with tomato and broccoli.

    Science.gov (United States)

    Canene-Adams, Kirstie; Sfanos, Karen S; Liang, Chung-Tiang; Yegnasubramanian, Srinivasan; Nelson, William G; Brayton, Cory; De Marzo, Angelo M

    2013-01-01

    The heterocyclic amine, 2-amino-1-methyl-6-phenylimidazo[4,5-B]pyridine (PhIP), found in meats cooked at high temperatures, has been implicated in epidemiological and rodent studies for causing breast, prostate, and colorectal cancers. A previous animal study using a xenograft model has shown that whole tomato and broccoli, when eaten in combination, exhibit a marked effect on tumor reduction compared to when eaten alone. Our aim was to determine if PhIP-induced carcinogenesis can be prevented by dietary consumption of whole tomato + broccoli powders. Male Fischer 344 rats (n = 45) were randomized into the following treatment groups: control (AIN93G diet), PhIP (200 ppm in AIN93G diet for the first 20 weeks of the study), or tomato + broccoli + PhIP (mixed in AIN93G diet at 10% each and fed with PhIP for 20 weeks, and then without PhIP for 32 weeks). Study animals were monitored for 52 weeks and were euthanized as necessary based on a set of criteria for health status and tumor burden. Although there appeared to be some hepatic and intestinal toxicity due to the combination of PhIP and tomato + broccoli, these rodents had improved survival and reduced incidence and/or severity of PhIP-induced neoplastic lesions compared to the PhIP-alone treated group. Rats eating tomato + broccoli exhibited a marked decrease in the number and size of cribiform prostatic intraepitheilial neoplasia/carcinoma in situ (cribiform PIN/CIS) lesions and in the incidence of invasive intestinal adenocarcinomas and skin carcinomas. Although the apparent toxic effects of combined PhIP and tomato + broccoli need additional study, the results of this study support the hypothesis that a diet rich in tomato and broccoli can reduce or prevent dietary carcinogen-induced cancers.

  1. Dietary Chemoprevention of PhIP Induced Carcinogenesis in Male Fischer 344 Rats with Tomato and Broccoli

    Science.gov (United States)

    Canene-Adams, Kirstie; Sfanos, Karen S.; Liang, Chung-Tiang; Yegnasubramanian, Srinivasan; Nelson, William G.; Brayton, Cory; De Marzo, Angelo M.

    2013-01-01

    The heterocyclic amine, 2-amino-1-methyl-6-phenylimidazo[4,5-B]pyridine (PhIP), found in meats cooked at high temperatures, has been implicated in epidemiological and rodent studies for causing breast, prostate, and colorectal cancers. A previous animal study using a xenograft model has shown that whole tomato and broccoli, when eaten in combination, exhibit a marked effect on tumor reduction compared to when eaten alone. Our aim was to determine if PhIP-induced carcinogenesis can be prevented by dietary consumption of whole tomato + broccoli powders. Male Fischer 344 rats (n = 45) were randomized into the following treatment groups: control (AIN93G diet), PhIP (200 ppm in AIN93G diet for the first 20 weeks of the study), or tomato + broccoli + PhIP (mixed in AIN93G diet at 10% each and fed with PhIP for 20 weeks, and then without PhIP for 32 weeks). Study animals were monitored for 52 weeks and were euthanized as necessary based on a set of criteria for health status and tumor burden. Although there appeared to be some hepatic and intestinal toxicity due to the combination of PhIP and tomato + broccoli, these rodents had improved survival and reduced incidence and/or severity of PhIP-induced neoplastic lesions compared to the PhIP-alone treated group. Rats eating tomato + broccoli exhibited a marked decrease in the number and size of cribiform prostatic intraepitheilial neoplasia/carcinoma in situ (cribiform PIN/CIS) lesions and in the incidence of invasive intestinal adenocarcinomas and skin carcinomas. Although the apparent toxic effects of combined PhIP and tomato + broccoli need additional study, the results of this study support the hypothesis that a diet rich in tomato and broccoli can reduce or prevent dietary carcinogen-induced cancers. PMID:24312188

  2. Suppression of colitis-related mouse colon carcinogenesis by a COX-2 inhibitor and PPAR ligands

    OpenAIRE

    Sugie Shigeyuki; Suzuki Rikako; Kohno Hiroyuki; Tanaka Takuji

    2005-01-01

    Abstract Background It is generally assumed that inflammatory bowel disease (IBD)-related carcinogenesis occurs as a result of chronic inflammation. We previously developed a novel colitis-related mouse colon carcinogenesis model initiated with azoxymethane (AOM) and followed by dextran sodium sulfate (DSS). In the present study we investigated whether a cyclooxygenase (COX)-2 inhibitor nimesulide and ligands for peroxisome proliferator-activated receptors (PPARs), troglitazone (a PPARγ ligan...

  3. The Role of HPV E6 and E7 Oncoproteins in HPV-associated Cervical Carcinogenesis

    OpenAIRE

    Yim, Eun-Kyoung; Park, Jong-Sup

    2005-01-01

    Cervical cancer is one of the leading world causes of cancer morbidity and mortality in woman, with more than 98% related to a human papillomavirus (HPV) infection origin. Infection with specific subtypes of HPV has been strongly implicated in cervical carcinogenesis. The identification and functional verification of host proteins associated with HPV E6 and E7 oncoproteins may provide useful information in understanding cervical carcinogenesis and the development of cervical cancer-specific m...

  4. The interactions of dietary tomato powder and soy germ on prostate carcinogenesis in the TRAMP model

    OpenAIRE

    Zuniga, Krystle E.; Clinton, Steven K.; Erdman, John W.

    2013-01-01

    The interactions between bioactive rich food components within a complex human diet for the inhibition of prostate carcinogenesis (PCa) are largely unknown and difficult to quantify in humans. Tomato and soy products have each shown anti-PCa activity in laboratory studies. The objective of this study was to determine the efficacy of dietary tomato and soy germ, alone and in combination, for the inhibition of prostate carcinogenesis in the transgenic adenocarcinoma of the mouse prostate (TRAMP...

  5. Disease Heterogeneity and Immune Biomarkers in Preclinical Mouse Models of Ovarian Carcinogenesis

    Science.gov (United States)

    2015-10-01

    1 Award Number: W81XWH-10-1-0525 TITLE: Disease Heterogeneity and Immune Biomarkers in Preclinical Mouse Models of Ovarian Carcinogenesis...Disease Heterogeneity and Immune Biomarkers in Preclinical Mouse Models of Ovarian Carcinogenesis Magee Womens Research Institute 204 Craft Ave...KrasPten mice Aim 2: To profile disease heterogeneity and to identify immune biomarkers of natural and vaccine-induced immune responses in mice with

  6. Iatrogenic colorectal Kaposi sarcoma complicating a refractory ...

    African Journals Online (AJOL)

    Kaposi sarcoma is a mesenchymal tumor associated to a human herpes virus-8. It often occurs in human immunodeficiency virus-positive subjects. Colorectal localization is rare. We report the case of a colorectal Kaposi sarcoma complicating a refractory ulcerative colitis treated with surgery after the failure of ...

  7. Colorectal Cancer Rates by Race and Ethnicity

    Science.gov (United States)

    ... Language: English (US) Español (Spanish) Recommend on Facebook Tweet Share Compartir The rate of people getting colorectal cancer or dying from colorectal cancer varies by race and ethnicity. Incidence Rates by Race/Ethnicity and Sex “Incidence rate” means how many people out of a given number ...

  8. Tailored Telephone Counseling Increases Colorectal Cancer Screening

    Science.gov (United States)

    Rawl, Susan M.; Christy, Shannon M.; Monahan, Patrick O.; Ding, Yan; Krier, Connie; Champion, Victoria L.; Rex, Douglas

    2015-01-01

    To compare the efficacy of two interventions to promote colorectal cancer screening participation and forward stage movement of colorectal cancer screening adoption among first-degree relatives of individuals diagnosed with adenomatous polyps. One hundred fifty-eight first-degree relatives of individuals diagnosed with adenomatous polyps were…

  9. Vitamin D, inflammation, and colorectal cancer progression

    NARCIS (Netherlands)

    Harten-Gerritsen, van Suzanne; Balvers, Michiel G.J.; Witkamp, Renger F.; Kampman, Ellen; Duijnhoven, van F.J.B.

    2015-01-01

    Survival from colorectal cancer is positively associated with vitamin D status. However, whether this association is causal remains unclear. Inflammatory processes may link vitamin D to colorectal cancer survival, and therefore investigating inflammatory markers as potential mediators may be a

  10. Modern management of colorectal liver metastases

    African Journals Online (AJOL)

    Colorectal cancer is one of the commonest malignancies worldwide. e liver is the most frequent site of metastasis from colorectal cancer and overall close to 50% of patients will develop liver metastases during the course of the disease. In one- third of patients, the liver metastases are synchronous, i.e. present at the time of.

  11. Indeterminate Pulmonary Nodules at Colorectal Cancer Staging

    DEFF Research Database (Denmark)

    Nordholm-Carstensen, Andreas; Wille-Jørgensen, Peer A; Jorgensen, Lars N

    2013-01-01

    This study aimed to estimate the prevalence of indeterminate pulmonary nodules and specific radiological and clinical characteristics that predict malignancy of these at initial staging chest computed tomography (CT) in patients with colorectal cancer. A considerable number of indeterminate...... pulmonary nodules, which cannot readily be classified as either benign or malignant, are detected at initial staging chest CT in colorectal cancer patients....

  12. Short-term carcinogenesis evaluation of Casearia sylvestris

    Directory of Open Access Journals (Sweden)

    Cleide A.S. Tirloni

    Full Text Available Abstract Casearia sylvestris Sw., Salicaceae, is an important medicinal plant widely used in Brazil for the treatment of various cardiovascular disorders. This species was included as of interest by Brazilian Unified Health System. Although preclinical studies described cardiovascular protective effects and apparent absence of toxicity, no studies have evaluated its carcinogenic potential. In this study, we proposed a short-term carcinogenesis evaluation of C. sylvestris in Wistar rats, aiming to check the safety of this species to use it as proposed by Brazilian Unified Health System. C. sylvestris leaves were obtained and the crude extract was prepared by maceration from methanol/water. Wistar rats were orally treated for 12 weeks with 50, 250 or 500 mg kg−1 of crude extract or vehicle. Body weight, daily morbidity and mortality were monitored. Blood and bone marrow samples were collect for micronucleus test, comet assay and tumor markers evaluation. Vital organs were removed to macro and histopathological analyses. The crude extract did not induce mutagenic and genotoxic effects and no alterations were observed in important tumor markers. Finally, no detectable signs of injury through gross pathology or histopathological examinations were observed. Our results certify the absence of the crude extract toxicity, indicating its safety, even at prolonged exposure as proposed by Brazilian Unified Health System.

  13. Hydrophobic bile acids, genomic instability, Darwinian selection, and colon carcinogenesis

    Directory of Open Access Journals (Sweden)

    Claire M Payne

    2008-12-01

    Full Text Available Claire M Payne, Carol Bernstein, Katerina Dvorak, Harris BernsteinDepartment of Cell Biology and Anatomy, College of Medicine, University of Arizona, Tucson, Arizona, USAAbstract: Sporadic colon cancer is caused predominantly by dietary factors. We have selected bile acids as a focus of this review since high levels of hydrophobic bile acids accompany a Western-style diet, and play a key role in colon carcinogenesis. We describe how bile acid-induced stresses cause cell death in susceptible cells, contribute to genomic instability in surviving cells, impose Darwinian selection on survivors and enhance initiation and progression to colon cancer. The most likely major mechanisms by which hydrophobic bile acids induce stresses on cells (DNA damage, endoplasmic reticulum stress, mitochondrial damage are described. Persistent exposure of colon epithelial cells to hydrophobic bile acids can result in the activation of pro-survival stress-response pathways, and the modulation of numerous genes/proteins associated with chromosome maintenance and mitosis. The multiple mechanisms by which hydrophobic bile acids contribute to genomic instability are discussed, and include oxidative DNA damage, p53 and other mutations, micronuclei formation and aneuploidy. Since bile acids and oxidative stress decrease DNA repair proteins, an increase in DNA damage and increased genomic instability through this mechanism is also described. This review provides a mechanistic explanation for the important link between a Western-style diet and associated increased levels of colon cancer.Keywords: bile acids, genomic instability, colon cancer

  14. Dysregulated hepatic bile acids collaboratively promote liver carcinogenesis.

    Science.gov (United States)

    Xie, Guoxiang; Wang, Xiaoning; Huang, Fengjie; Zhao, Aihua; Chen, Wenlian; Yan, Jingyu; Zhang, Yunjing; Lei, Sha; Ge, Kun; Zheng, Xiaojiao; Liu, Jiajian; Su, Mingming; Liu, Ping; Jia, Wei

    2016-10-15

    Dysregulated bile acids (BAs) are closely associated with liver diseases and attributed to altered gut microbiota. Here, we show that the intrahepatic retention of hydrophobic BAs including deoxycholate (DCA), taurocholate (TCA), taurochenodeoxycholate (TCDCA), and taurolithocholate (TLCA) were substantially increased in a streptozotocin and high fat diet (HFD) induced nonalcoholic steatohepatitis-hepatocellular carcinoma (NASH-HCC) mouse model. Additionally chronic HFD-fed mice spontaneously developed liver tumors with significantly increased hepatic BA levels. Enhancing intestinal excretion of hydrophobic BAs in the NASH-HCC model mice by a 2% cholestyramine feeding significantly prevented HCC development. The gut microbiota alterations were closely correlated with altered BA levels in liver and feces. HFD-induced inflammation inhibited key BA transporters, resulting in sustained increases in intrahepatic BA concentrations. Our study also showed a significantly increased cell proliferation in BA treated normal human hepatic cell lines and a down-regulated expression of tumor suppressor gene CEBPα in TCDCA treated HepG2 cell line, suggesting that several hydrophobic BAs may collaboratively promote liver carcinogenesis. © 2016 UICC.

  15. Recent Concepts of Ovarian Carcinogenesis: Type I and Type II

    Directory of Open Access Journals (Sweden)

    Masafumi Koshiyama

    2014-01-01

    Full Text Available Type I ovarian tumors, where precursor lesions in the ovary have clearly been described, include endometrioid, clear cell, mucinous, low grade serous, and transitional cell carcinomas, while type II tumors, where such lesions have not been described clearly and tumors may develop de novo from the tubal and/or ovarian surface epithelium, comprise high grade serous carcinomas, undifferentiated carcinomas, and carcinosarcomas. The carcinogenesis of endometrioid and clear cell carcinoma (CCC arising from endometriotic cysts is significantly influenced by the free iron concentration, which is associated with cancer development through the induction of persistent oxidative stress. A subset of mucinous carcinomas develop in association with ovarian teratomas; however, the majority of these tumors do not harbor any teratomatous component. Other theories of their origin include mucinous metaplasia of surface epithelial inclusions, endometriosis, and Brenner tumors. Low grade serous carcinomas are thought to evolve in a stepwise fashion from benign serous cystadenoma to a serous borderline tumor (SBT. With regard to high grade serous carcinoma, the serous tubal intraepithelial carcinomas (STICs of the junction of the fallopian tube epithelium with the mesothelium of the tubal serosa, termed the “tubal peritoneal junction” (TPJ, undergo malignant transformation due to their location, and metastasize to the nearby ovary and surrounding pelvic peritoneum. Other theories of their origin include the ovarian hilum cells.

  16. RANKL Signaling and ErbB Receptors in Breast Carcinogenesis.

    Science.gov (United States)

    Zoi, Ilianna; Karamouzis, Michalis V; Adamopoulos, Christos; Papavassiliou, Athanasios G

    2016-10-01

    ErbB family members, ErbB1/EGFR/HER-1, ErbB2/HER-2, ErbB3/HER-3 and ErbB4/HER-4, have been implicated in breast cancer (BC) tumorigenicity. Recently, crucial roles for RANK/RANKL signaling in addition to key downstream factor NF-κB have been demonstrated in mammary tumorigenesis. Here, we present the hypothesis of a novel association between ErbB and RANK pathways in promoting BC. The proposed model alludes to the cross-talk that might occur between RANK and ErbB receptors. This interplay might regulate RANK signaling and consequently, modulate carcinogenesis, mainly in ErbB2 over-expressing BC cells. Thus, we highlight the significance of the RANK/RANKL axis as a putative therapeutic target in this malignancy, and furthermore, suggest that the combination of ErbB and RANK/RANKL inhibitors may have therapeutic benefit for certain BC patients. Copyright © 2016 Elsevier Ltd. All rights reserved.

  17. Genetic and Epigenetic Biomarkers of Molecular Alterations in Oral Carcinogenesis.

    Science.gov (United States)

    Dumache, Raluca; Rogobete, Alexandru Florin; Andreescu, Nicoleta; Puiu, Maria

    2015-01-01

    Worldwide, oral cancers represent the 6th most common type of cancer. Oral squamous cell carcinoma (OSCC), which is the most common type of oral cancer, is present in about 90% of the patients with this malignancy. OSCC presents a survival rate up to 80%, if it is detected in an early stage (T1), but if detected at later stages (T3 - T4) the survival rate decreases to 20 - 30%. Due to these survival rates, it is obvious that there is an urgent need to introduce new molecular biomarkers for the early, noninvasive diagnosis of oral cancers from saliva. These biomarkers will aid in increasing the survival rate of the patients for the long-term. MicroRNAs are part of a class of small, non-coding RNAs that contain 19 - 23 nucleotides. MicroRNAs play an important role in the regulation of biochemical mechanisms, cell proliferation, and other cellular mechanisms in the human body. Recently, due to the developments in the field of molecular genetics, salivary microRNAs became important biomarkers in early detection and monitoring of oral cancers by noninvasive methods. We want to present in this review the most important genetic and epigenetic biomarkers involved in oral carcinogenesis, focusing especially on the salivary microRNAs as biomarkers in early diagnosis of OSCC.

  18. Colorectal Cancer Awareness for Women via Facebook: A Pilot Study.

    Science.gov (United States)

    Brittain, Kelly; Pennings Kamp, Kendra J; Salaysay, Zachary

    Colorectal cancer is the third leading cause of cancer death among U.S. women. Women report being screened for colorectal cancer less often than men, and if colorectal cancer screening guidelines were routinely followed, approximately 60% of colorectal cancer deaths could be prevented. Many colorectal cancer screening interventions have not used Facebook, which is the most popular social media site among women. Little is known about engaging women in colorectal cancer screening and risk reduction information using Facebook. The "Colorectal Cancer Screening Awareness for Women" Facebook page was created to promote colorectal cancer screening and risk reduction awareness among women. Facebook posts targeted women aged 45-64 years and highlighted colorectal cancer screening methods, guidelines, and colorectal cancer risk reduction strategies. Demographics and data about the women's interactions with the page were collected using Facebook analytics and analyzed. The majority of the 391 users of the Colorectal Cancer Screening Awareness for Women Facebook page were women aged 45-54 years (56.5%). The most "liked" posts were related to colorectal cancer risk reduction behaviors. In an effort to increase routine colorectal cancer screening and colorectal cancer risk reduction behaviors, gastroenterology nurses and practices should consider Facebook as a good method to regularly engage women in colorectal cancer screening and colorectal cancer risk reduction information.

  19. The properties of red seaweed (Kappaphycus alvarezii) and its effect on mammary carcinogenesis.

    Science.gov (United States)

    Chang, Vi-Sion; Okechukwu, Patrick N; Teo, Swee-Sen

    2017-03-01

    The edible red seaweed (Kappaphycus alvarezii) is one of the algae species which was found to be rich in nutrients and nutraceutical. Hence, K. alvarezii may have the ability to suppress cancer through its antiproliferative properties. The aim of this study was to investigate the potential compounds of K. alvarezii, cytotoxicity properties of K. alvarezii extract on breast cancer cell line (MCF-7), investigated toxicity effect of high dosage K. alvarezii extract in rats and determined the effect of K. alvarezii on 7, 12-dimethylbenz[a]anthracene (DMBA) mammary carcinogenesis in rats. The method of LCMS/MS and MTT assay were used. For animal study, sub-chronic toxicity method was used, the rats were supplemented with 2000mg/kg body weight daily of K. alvarezii crude extracts by oral gavage. For the anticancer effect of K. alvarezii crude extracts, this study consisted of three groups of the experimental, untreated and normal group of rats. The experimental and untreated groups of rats were induced with mammary tumour with DMBA. The experimental group of rats was given with K. alvarezii crude extracts orally. The results were being used to compare with the untreated group of rats and normal group of rats. All the rats were fed with standard diet and water ad libitum. Mortality, behavior changes and tumour sizes were observed specifically. The differences between the three groups of rats were evaluated by using the ANOVA test. By using LCMS/MS method, six unknown compounds were analysed. K. alvarezii crude extract reduced the cell viability of MCF-7 from 84.91% to 0.81% and the IC50 value is 4.1±0.69mg/mL. For sub-chronic and heavy metal toxicity studies, no significant difference was found in haematological and biochemical values of the control group and experimental group. The growth rate of tumours in the untreated group of rats was found significantly higher than the experimental group of rats. Besides that, the white blood cells level in untreated group was

  20. Effects of a health education and telephone counseling program on patients with a positive fecal occult blood test result for colorectal cancer screening: A randomized controlled trial.

    Science.gov (United States)

    Chiu, Hui-Chuan; Hung, Hsin-Yuan; Lin, Hsiu-Chen; Chen, Shu-Ching

    2017-10-01

    Our purpose was to evaluate the effects of a health education and telephone counseling program on knowledge and attitudes about colorectal cancer and screening and the psychological impact of positive screening results. A randomized controlled trial was conducted with 2 groups using a pretest and posttest measures design. Patients with positive colorectal cancer screening results were selected and randomly assigned to an experimental (n = 51) or control (n = 51) group. Subjects in the experimental group received a health education and telephone counseling program, while the control group received routine care only. Patients were assessed pretest before intervention (first visit to the outpatient) and posttest at 4 weeks after intervention (4 weeks after first visit to the outpatient). Patients in the experimental group had a significantly better level of knowledge about colorectal cancer and the psychological impact of a positive screening result than did the control group. Analysis of covariance revealed that the health education and telephone counseling program had a significant main effect on colorectal cancer knowledge. A health education and telephone counseling program can improve knowledge about colorectal cancer and about the psychological impact in patients with positive colorectal cancer screening results. The health education and telephone counseling program is an easy, simple, and convenient method of improving knowledge, improving attitudes, and alleviating psychological distress in patients with positive colorectal cancer screening results, and this program can be expanded to other types of cancer screening. Copyright © 2016 John Wiley & Sons, Ltd.