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Sample records for hydrazine induced colorectal

  1. Effect of kaempferol on lipid peroxidation and antioxidant status in 1,2-dimethyl hydrazine induced colorectal carcinoma in rats.

    Science.gov (United States)

    Nirmala, Parthasarathy; Ramanathan, Manickam

    2011-03-01

    Colorectal cancer, a common cause of cancer related deaths in both sexes in western population is often due to persistent oxidative stress leading to DNA damage. Antioxidants scavenge free radicals and inhibit neoplastic process. Kaempferol, a flavonol widely distributed in tea, broccoli, grape fruit, brussels sprouts and apple, is claimed to have chemopreventive action in colon cancer. The aim of our study was to evaluate the effect of kaempferol on tissue lipid peroxidation and antioxidant status in 1,2-dimethyl hydrazine induced colorectal cancer in male Wistar rats and to compare its efficacy with irinotecan. Experimental colon cancer induced by 1,2-dimethyl hydrazine in rats mimic human colon cancer and therefore is an ideal model for chemoprevention studies. The rats were divided into six groups. Group 1 served as control. Group 2 received 1,2-dimethyl hydrazine (20 mg/kg body weight) subcutaneously once a week for four weeks. Group 3 received irinotecan (100 mg/kg body weight) intravenously once a week for four weeks with 1,2-dimethyl hydrazine. Groups 4 to 6 were given a daily oral dose of 50, 100, 200 mg/kg body weight of kaempferol with 1,2-dimethyl hydrazine. The total study period was 16 weeks. Kaempferol supplementation lowered 1,2-dimethyl hydrazine induced erythrocyte lysate and liver thiobarbituric acid reactive substances level and rejuvenated anti oxidant enzymes catalase, super oxide dismutase and glutathione peroxidase. The recovery of enzyme status was maximum at the dose of 200 mg/kg body weight and was comparable to irinotecan. Our study reveals that kaempferol could be safely used as a chemopreventive agent in colorectal cancer.

  2. Fixation and loss of hydrazine-induced premutational damage in Haemophilus influenzae

    Energy Technology Data Exchange (ETDEWEB)

    Kimball, R.F.; Hirsch, B.F.

    1976-01-01

    Premutational damage induced in Haemophilus influenzae by hydrazine appears to be fixed as final mutation only at replication as judged by the transformation assay. Fixation at replication is independent of the rec 1 gene, unlike the case with nitrosocarbaryl. Prior to replication premutational damage induced by hydrazine disappears by an unknown process that is not dependent on the presence of a pyrimidine dimer excision system nor on the rec 1 gene. Hydrazine does not produce detectable single-strand breaks or alkali-labile sites in the treated DNA nor gaps in DNA newly synthesized after treatment. In these respects it also differs from nitroso compounds. It is concluded that hydrazine acts to produce an altered base, possibly N(4)-aminocytosine, that produces mutations by mispairing at replication rather than by error-prone repair.

  3. Oxaliplatin-induced neuropathy in colorectal cancer

    DEFF Research Database (Denmark)

    Zedan, Ahmed; Hansen, Torben Frøstrup; Fex Svenningsen, Åsa

    2014-01-01

    Oxaliplatin is a chemotherapeutic agent effective against advanced colorectal cancer. Unlike with other platinum-based agents, the main side effect of oxaliplatin is polyneuropathy. Oxaliplatin-induced polyneuropathy (OIPN) has a unique profile, which can be divided into acute and chronic...

  4. Oxaliplatin-induced neuropathy in colorectal cancer

    DEFF Research Database (Denmark)

    Zedan, Ahmed; Hansen, Torben Frøstrup; Fex Svenningsen, Åsa

    2014-01-01

    Oxaliplatin is a chemotherapeutic agent effective against advanced colorectal cancer. Unlike with other platinum-based agents, the main side effect of oxaliplatin is polyneuropathy. Oxaliplatin-induced polyneuropathy (OIPN) has a unique profile, which can be divided into acute and chronic...

  5. Sensitized Liquid Hydrazine Detonation Studies

    Science.gov (United States)

    Rathgeber, K. A.; Keddy, C. P.; Bunker, R. L.

    1999-01-01

    Vapor-phase hydrazine (N2H4) is known to be very sensitive to detonation while liquid hydrazine is very insensitive to detonation, theoretically requiring extremely high pressures to induce initiation. A review of literature on solid and liquid explosives shows that when pure explosive substances are infiltrated with gas cavities, voids, and/or different phase contaminants, the energy or shock pressure necessary to induce detonation can decrease by an order of magnitude. Tests were conducted with liquid hydrazine in a modified card-gap configuration. Sensitization was attempted by bubbling helium gas through and/or suspending ceramic microspheres in the liquid. The hydrazine was subjected to the shock pressure from a 2 lb (0.9 kg) Composition C-4 explosive charge. The hydrazine was contained in a 4 in. (10.2 cm) diameter stainless steel cylinder with a 122 in(sup 3) (2 L) volume and sealed with a polyethylene cap. Blast pressures from the events were recorded by 63 high speed pressure transducers located on three radial legs extending from 4 to 115 ft (1.2 to 35.1 in) from ground zero. Comparison of the neat hydrazine and water baseline tests with the "sensitized" hydrazine tests indicates the liquid hydrazine did not detonate under these conditions.

  6. Hydrazine borane-induced destabilization of ammonia borane, and vice versa

    Energy Technology Data Exchange (ETDEWEB)

    Petit, Jean-Fabien; Moussa, Georges [IEM (Institut Europeen des Membranes), UMR 5635 (CNRS-ENSCM-UM2), Universite Montpellier 2, Place E. Bataillon, F-34095 Montpellier (France); Demirci, Umit B., E-mail: umit.demirci@um2.fr [IEM (Institut Europeen des Membranes), UMR 5635 (CNRS-ENSCM-UM2), Universite Montpellier 2, Place E. Bataillon, F-34095 Montpellier (France); Toche, François; Chiriac, Rodica [Université Lyon 1, CNRS, UMR 5615, Laboratoire des Multimatériaux et Interfaces, 43 boulevard du 11 Novembre 1918, F-69622 Villeurbanne (France); Miele, Philippe [IEM (Institut Europeen des Membranes), UMR 5635 (CNRS-ENSCM-UM2), Universite Montpellier 2, Place E. Bataillon, F-34095 Montpellier (France)

    2014-08-15

    Graphical abstract: - Highlights: • Hydrazine borane and ammoniaborane (mole ratio 1:1) destabilize each other. • This is characterized by a melting point at ∼30 °C and decomposition into hydrazine. • Also, some hydrogen H{sub 2} is “explosively” liberated at around 90 °C. • The mixture can be however stabilized into a potential hydrogen storage material. • This hydrogen storage material dehydrogenates up to 300 °C to form boron nitride. - Abstract: In the field of solid-state chemical hydrogen storage, ammonia borane NH{sub 3}BH{sub 3} has been widely studied while hydrazine borane N{sub 2}H{sub 4}BH{sub 3} can be considered as a “novel” material. In the present work, we investigated the behaviour of these boranes when mixed together in a mole ratio of 1:1. Hydrazine borane and ammonia borane destabilize each other. Though stable at 20–25 °C, the mixture melts at ∼30 °C and then undergoes significant decomposition, with desorption of hydrogen H{sub 2} and hydrazine N{sub 2}H{sub 4} from 67 °C. This is explained by the fact that the presence of hydrazine borane disrupts the H{sup δ+}⋯H{sup δ−} network of ammonia borane, and vice versa; the mixture is then much less stable than the pristine boranes. The mixture can nevertheless be stabilized (by heat- or vacuum-treatment and thus extraction of evolving hydrogen and hydrazine), making the as-obtained solid a potential chemical hydrogen storage material. Over the range 25–300 °C, it is able to release ca. 11.4 wt% of almost pure H{sub 2}. Furthermore forms boron nitride as the solid residue, at temperatures as low as 300 °C.

  7. Sambar, an Indian Dish Prevents the Development of Dimethyl Hydrazine-Induced Colon Cancer: A Preclinical Study.

    Science.gov (United States)

    Prasad, Vutturu Ganga; Reddy, Neetinkumar; Francis, Albi; Nayak, Pawan G; Kishore, Anoop; Nandakumar, Krishnadas; Rao, Mallikarjuna C; Shenoy, Rekha

    2016-07-01

    Colon cancer (CC) is the third commonly diagnosed cancer and the second leading cause of mortality in the US when compared to India where prevalence is less. Possible reason could be the vegetarian diet comprising spices used in curry powders. Researchers believe that 70% of the cases are associated with diet. Spices have inherited a rich tradition for their flavor and medicinal properties. Researchers have been oriented towards spices present in food items for their antitumorigenic properties. We investigated the effects of sambar as a preventive measure for 1,2-dimethyl hydrazine (DMH)-induced CC in Wistar albino rats. The animals were divided into three groups (n = 6) namely control, DMH, and sambar. At the end of the experimental period, the animals were killed using anesthesia and the colons and livers were examined. All the treatment groups exhibited a significant change in the number of aberrant crypt foci (ACF). Sambar group showed a significant change in the colonic GSH when compared to both normal and DMH groups. A significant reduction in the liver GSH was noted in the sambar group. Only sambar group showed a significant change in the liver catalase levels when compared to DMH. There was a significant reduction in the colonic nitrite in the sambar-treated group; 2.94 ± 0.29 when compared to DMH control at 8.09 ± 1.32. On the contrary, a significant rise in the liver nitrite levels was observed in the sambar-treated rats. Sambar may prevent the risk of CC when consumed in dietary proportions. Consumption of sambar significantly reduced aberrant crypt foci in DMH-induced colon cancer modelSambar treatment prevented DMH-induced oxidative changes in the colonic tissue, indicating its antioxidant roleSambar comprises a variety of spices that exhibited both pro- and antioxidant properties in different tissues, leading to its overall beneficial effect in this model. Abbreviations used: ACF: aberrant crypt foci, CC: colon cancer, DMH: 1,2-dimethyl hydrazine

  8. The catalysis of hydrazines

    Science.gov (United States)

    Tanatar, S.

    1987-01-01

    Hydrazine sulfate in a hot aqueous solution can be catalyzed in the direction of 3 N2H4 = 4 NH3 + N2. Free hydrazine in a hot aqueous solution dissociates in the presence of platinum in the following direction: 2 N2H4 = 2 NH3 + N2 + H2. In the presence of sodium hydroxide, the catalytic dissociation of hydrazine takes a third direction: 3 N2H4 = 2 NH3 + 2 N3 + 3 H2.

  9. Clinical Aspects of Hypoxia-inducible Factors in Colorectal Cancer

    DEFF Research Database (Denmark)

    Havelund, Birgitte Mayland; Spindler, Karen-Lise Garm; Sørensen, Flemming Brandt;

    to a standardized scheme. 2. The prognostic value of HIF-1α is investigated by SNP analysis and HIF-1α expression in tissue from 300 patients operated for colorectal cancer and the results is validated in a prospectively population of 200 patients. 3. The predictive value of HIF-1α will be investigated in patients......Clinical Aspects of Hypoxia-inducible Factors in Colorectal Cancer   Birgitte Mayland Havelund1,4 MD, Karen-Lise Garm Spindler1,4 MD, PhD, Flemming Brandt Sørensen2,4 MD, DMSc, Ivan Brandslund3 MD, DMSc, Anders Jakobsen1,4 MD, DMSc. 1Department of Oncology, 2Pathology and 3Biochemistry, Vejle...... Hospital, Vejle, Denmark 4Institute of Regional Health Services Research, University of Southern Denmark, Odense Denmark Background Prognostic and predictive markers are needed for individualizing the treatment of colorectal cancer. Hypoxia-inducible factor 1α (HIF-1α) is a transcription-inducing factor...

  10. Cytokine-Induced Modulation of Colorectal Cancer.

    Science.gov (United States)

    Mager, Lukas F; Wasmer, Marie-Hélène; Rau, Tilman T; Krebs, Philippe

    2016-01-01

    The emergence of novel immunomodulatory cancer therapies over the last decade, above all immune checkpoint blockade, has significantly advanced tumor treatment. For colorectal cancer (CRC), a novel scoring system based on the immune cell infiltration in tumors has greatly improved disease prognostic evaluation and guidance to more specific therapy. These findings underline the relevance of tumor immunology in the future handling and therapeutic approach of malignant disease. Inflammation can either promote or suppress CRC pathogenesis and inflammatory mediators, mainly cytokines, critically determine the pro- or anti-tumorigenic signals within the tumor environment. Here, we review the current knowledge on the cytokines known to be critically involved in CRC development and illustrate their mechanisms of action. We also highlight similarities and differences between CRC patients and murine models of CRC and point out cytokines with an ambivalent role for intestinal cancer. We also identify some of the future challenges in the field that should be addressed for the development of more effective immunomodulatory therapies.

  11. Gliotoxin Inhibits Proliferation and Induces Apoptosis in Colorectal Cancer Cells

    Directory of Open Access Journals (Sweden)

    Junxiong Chen

    2015-10-01

    Full Text Available The discovery of new bioactive compounds from marine natural sources is very important in pharmacological research. Here we developed a Wnt responsive luciferase reporter assay to screen small molecule inhibitors of cancer associated constitutive Wnt signaling pathway. We identified that gliotoxin (GTX and some of its analogues, the secondary metabolites from marine fungus Neosartorya pseufofischeri, acted as inhibitors of the Wnt signaling pathway. In addition, we found that GTX downregulated the β-catenin levels in colorectal cancer cells with inactivating mutations of adenomatous polyposis coli (APC or activating mutations of β-catenin. Furthermore, we demonstrated that GTX induced growth inhibition and apoptosis in multiple colorectal cancer cell lines with mutations of the Wnt signaling pathway. Together, we illustrated a practical approach to identify small-molecule inhibitors of the Wnt signaling pathway and our study indicated that GTX has therapeutic potential for the prevention or treatment of Wnt dependent cancers and other Wnt related diseases.

  12. Enhanced therapeutic efficacy and amelioration of cisplatin-induced nephrotoxicity by quercetin in 1,2-dimethyl hydrazine-induced colon cancer in rats.

    Science.gov (United States)

    Li, Qing-Chun; Liang, Yun; Hu, Guang-Rui; Tian, Yuan

    2016-01-01

    The aim of quercetin treatment in combination of cisplatin (CP)-induced nephrotoxicity as well on 1,2-dimethyl hydrazine (DMH)-induced colon cancer. In this study, animals are exposed to DMH hydrochloride to induce colon cancer. In these groups, nephrotoxicity was assessed with the help of blood urea nitrogen, urea, and creatinine. The antitumor activity of quercetin and CP assessed with the help of number of aberrant crypts and foci formation. Tumor size in different treatment group determined with the help of vernier caliper. CP is one of the most widely used antineoplastic drugs against colon cancer, but it has a major dose-limiting drawbacks of causing nephrotoxicity. Therefore, there is a need for a novel therapeutic regimen which will reduce the nephrotoxicity and enhance the anticancer activity of CP. The protective effect of quercetin on CP-induced nephrotoxicity is well-known. Moreover, quercetin is proven to have antitumor activity in colon cancer. Keeping all the facts in view, this study was conceived to evaluate the role of quercetin on therapeutic efficacy and nephrotoxicity of CP in DMH-induced colon cancer in male Sprague-Dawley rats. Treatment of quercetin with CP (7.5 mg/kg) prevents the CP-induced nephrotoxicity along with enhance the anticancer activity confirmed by the reduction of aberrant crypt foci number. Treatment of CP and quercetin alone leads to significant increase in the anticancer activity as compared to control colon tumor rats. In DMH-induced colon cancer model, combination of quercetin and CP ameliorates CP-induced nephrotoxicity as well as enhanced antitumor activity.

  13. Hydrazine inactivates bacillus spores

    Science.gov (United States)

    Schubert, Wayne; Plett, G. A.; Yavrouian, A. H.; Barengoltz, J.

    2005-01-01

    Planetary Protection places requirements on the maximum number of viable bacterial spores that may be delivered by a spacecraft to another solar system body. Therefore, for such space missions, the spores that may be found in hydrazine are of concern. A proposed change in processing procedures that eliminated a 0.2 um filtration step propmpted this study to ensure microbial contamination issue existed, especially since no information was found in the literature to substantiate bacterial spore inactivation by hydrazine.

  14. Research on the Reaction Between Technetium and Hydrazine in Nitric Acid Medium

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    The reaction between technetium and hydrazine in nitric acid medium was studied by the titration ofthe concentration of hydrazine and pursuing the concentration of heptavalent technetium along with time.It is approved that the reaction between technetium and hydrazine includes an inducing period, a fast

  15. COMPLEXES CONTAINING HYDRAZINE AND BENZYL ...

    African Journals Online (AJOL)

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    In previous reports, anhydrous hydrazine and substituted hydrazine were ... DRX 250 spectrometer while that of 3 was recorded on a Bruker 300 MHz instrument at ... The hydrazine complex was prepared from the polymer [{RuCl2(COD)}x] by the ... solution and the acetone was removed under reduced pressure and a white ...

  16. Adiponectin deficiency enhances colorectal carcinogenesis and liver tumor formation induced by azoxymethane in mice

    Institute of Scientific and Technical Information of China (English)

    Tamao Nishihara; Shinji Tamura; Norio Hayashi; Hiroyasu Iishi; Iichiro Shimornura; Miyako Baba; Morihiro Matsuda; Masahiro Inoue; Yasuko Nishizawa; Atsunori Fukuhara; Hiroshi Arald; Shinji Kihara; Tohru Funahashi

    2008-01-01

    AIM: To investigate the causal relationship between hypoadiponectinemia and colorectal carcinogenesis in in vivo experimental model, and to determine the con-tribution of adiponectin deficiency to colorectal cancer development and proliferation. METHODS: We examined the influence of adiponectin deficiency on colorectal carcinogenesis induced by the administration of azoxymethane (AOM) (7.5 mg/kg, in-traperitoneal injection once a week for 8 wk), by using adiponectin-knockout (KO) mice. RESULTS: At 53 wk after the first AOM treatment, KOmice developed larger and histologically more progres-sive colorectal tumors with greater frequency com-pared with wild-type (WT) mice, although the tumor incidence was not different between WT and KO mice. KO mice showed increased cell proliferation of colorec-tal tumor cells, which correlated with the expression levels of cyclooxygenase-2 (COX-2) in the colorectal tumors. In addition, KO mice showed higher incidence and frequency of liver tumors after AOI treatment. Thirteen percent of WT mice developed liver tumors, and these WT mice had only a single tumor. In contrast, 50% of K.O mice developed liver tumors, and 58% of these KO mice had multiple tumors. CONCLUSION: Adiponectin deficiency enhances colorectal carcinogenesis and liver tumor formation induced by AOM in mice. This study strongly suggests that hypoadiponectinemia could be involved in the pathogenesis for colorectal cancer and liver tumor in human subjects.

  17. Effect of coriander seed powder (CSP) on 1, 2-dimethyl hydrazine-induced changes in antioxidant enzyme system and lipid peroxide formation in rats.

    Science.gov (United States)

    Anilakumar, K R; Khanum, Farhath; Bawa, A S

    2010-03-01

    The effect of coriander seed powder (CSP), a culinary spice, on dimethyl hydrazine (DMH)-induced oxidative stress and toxicity in rats was investigated. Six groups of 6 male rats each were maintained for 12 weeks as (a) Control; (b) DMH (60 mg/kg body weight) injected; (c) 5% CSP incorporated diet; (d) 5% CSP incorporated diet + DMH; (e) 10% CSP incorporated diet; and (f) 10% CSP incorporated diet + DMH. The rats were sacrificed after 12 weeks. The results revealed that DMH administration lead to an increase in hepatic lipid peroxidation associated with reduction in levels of glutathione (GSH), activity of superoxide dismutase (SOD), and catalase and glucose-6-phosphate dehydrogenase. The coadministration of CSP and DMH diminished the hepatic malondialdehyde (MDA) significantly as compared to DMH-alone administered rats. The intake of coriander seeds at 10% level also enhanced the hepatic GSH-redox system by elevating GSH-Px, GSSGR, and GST activities. The DMH-induced decline in SOD and catalase activities was brought to normal by 10% CSP. The coadministration of CSP and the DMH produced a significant reduction in MDA and enhancement in catalase activity as compared to control. Coriander powder at 5% and 10% levels produced a significant rise in colonic catalase and GSH-Px. The coriander seeds produced significant beneficial effects by reducing the DMH-induced oxidative stress and enhancing the tissue levels of antioxidant/detoxification agent in tissues.

  18. Expression of survivin and p53 modulates honokiol-induced apoptosis in colorectal cancer cells.

    Science.gov (United States)

    Lai, Ying-Jiun; Lin, Chien-I; Wang, Chia-Lin; Chao, Jui-I

    2014-11-01

    Honokiol is a small biphenolic compound, which exerts antitumor activities; however, the precise mechanism of honokiol-induced apoptosis in the human colorectal cancer cells remains unclear. Here, we show that survivin and p53 display the opposite role on the regulation of honokiol-induced apoptosis in the human colorectal cancer cells. Honokiol induced the cell death and apoptosis in various colorectal cancer cell lines. Moreover, honokiol elicited the extrinsic death receptor pathway of DR5 and caspase 8 and the intrinsic pathway of caspase 9. The common intrinsic and extrinsic downstream targets of activated caspase 3 and PARP protein cleavage were induced by honokiol. Interestingly, honokiol reduced anti-apoptotic survivin protein and gene expression. Transfection with a green fluorescent protein (GFP)-survivin-expressed vector increased the colorectal cancer cell viability and resisted the honokiol-induced apoptosis. Meantime, honokiol increased total p53 and the phosphorylated p53 proteins at Ser15 and Ser46. The p53-wild type colorectal cancer cells were exhibited greater cytotoxicity, apoptosis and survivin reduction than the p53-null cancer cells after treatment with honokiol. Together, these findings demonstrate that the existence of survivin and p53 can modulate the honokiol-induced apoptosis in the human colorectal cancer cells.

  19. Great Market Potential of Hydrazine Hydrate

    Institute of Scientific and Technical Information of China (English)

    Shi Yuying

    2007-01-01

    @@ Stable consumption growth worldwide Hydrazine hydrate is an organic chemical raw material with extensive applications. The world's capacity to produce hydrazine hydrate has reached more than 200 thousand t/atoday (based on 100% hydrazine content).

  20. Toxicity assessment of hydrazine fuels

    Energy Technology Data Exchange (ETDEWEB)

    Keller, W.C.

    1988-11-01

    The major health aspects of exposure to hydrazine propellants are reviewed. Toxic effects of hydrazine fuels on humans and animals as well as in vitro studies are discussed with emphasis on recent findings and USAF studies. Propellant hydrazines have been found to be genotoxic in in vitro studies and oncogenic in animal studies. Embryotoxicity has been demonstrated at very high exposures but not at occupationally encountered levels for hydrazine and unsymmetrical dimethylhydrazine. Epidemiologic evidence to support these findings is lacking; however, the results of animal and in vitro studies have resulted in lowering both the time-weighted average-threshold limit values and short-term exposure limits for these propellants.

  1. Environmental Fate of Hydrazines

    Science.gov (United States)

    1989-12-01

    v/v. The absorbent cartridges removed trace gas contaminants , including remaining water and CO2 . Gas outlet-valves after each unit provided for air...largest kbkg was observed in Run A, presumably due to the interaction of hydrazine vapor with contamination on the chamber walls accumulated during its...64 UDMH Dry Air 2.8 19 13 1.1 a Ambirnt temperature, 50-75 ppm v/v initial concentrationb 24 m of added FEP c 14,700 ppm v/v water vapor Of these

  2. Approach for mechanism of BH3 domain counterpart BH3I-2′ inducing colorectal cancer cell apoptosis

    Institute of Scientific and Technical Information of China (English)

    FENG Wan-yu; LIU Yang; ZHANG Zhi-cheng

    2008-01-01

    Objective To discuss mechanism of BH3 domain counterpart BH3I-2' inducing colorectal cancer cell apoptosis. Methods Detected inhibition ratio and apoptosis of colorectal cancer cells HCT-116, which were treated by BH3I-2', with microplate reader and flow cytometry. Results Inhibition ratio of colorectal cancer cells, which were treated by BH3I-2', could reach about 50 %. Ratio of viable apoptotic cell decreased and that of non-viable apoptotie cell increased as time went. Conclusions BH3I-2' can induce colorectal cancer cell apoptosis.

  3. FGFR4 promotes stroma-induced epithelial-to-mesenchymal transition in colorectal cancer.

    Science.gov (United States)

    Liu, Rui; Li, Jingyi; Xie, Ke; Zhang, Tao; Lei, Yunlong; Chen, Yi; Zhang, Lu; Huang, Kai; Wang, Kui; Wu, Hong; Wu, Min; Nice, Edouard C; Huang, Canhua; Wei, Yuquan

    2013-10-01

    Tumor cells evolve by interacting with the local microenvironment; however, the tumor-stroma interactions that govern tumor metastasis are poorly understood. In this study, proteomic analyses reveal that coculture with tumor-associated fibroblasts (TAF) induces significant overexpression of FGFR4, but not other FGFRs, in colorectal cancer cell lines. Mechanistic study shows that FGFR4 plays crucial roles in TAF-induced epithelial-to-mesenchymal transition (EMT) in colorectal cancer cell lines. Accumulated FGFR4 in cell membrane phosphorylates β-catenin, leading to translocation of β-catenin into the nucleus. Further, TAF-derived CCL2 and its downstream transcription factor, Ets-1, are prerequisites for TAF-induced FGFR4 upregulation. Furthermore, FGFR4-associated pathways are shown to be preferentially activated in colorectal tumor samples, and direct tumor metastasis in a mouse metastasis model. Our study shows a pivotal role of FGFR4 in tumor-stroma interactions during colorectal cancer metastasis, and suggests novel therapeutic opportunities for the treatment of colorectal cancer.

  4. Management of chemotherapy-induced adverse effects in the treatment of colorectal cancer

    NARCIS (Netherlands)

    Jansman, FGA; Sleijfer, DT; de Graaf, JC; Coenen, JLLM; Brouwers, JRBJ

    2001-01-01

    The anticancer agents fluorouracil, raltitrexed, irinotecan and oxaliplatin show limited efficacy in the treatment of colorectal cancer and may be associated with substantial toxicity. Therefore, the prevention and reduction of chemotherapy-induced adverse effects is of major significance, in accord

  5. Hydrazine vapor inactivates Bacillus spores

    Science.gov (United States)

    Schubert, Wayne W.; Engler, Diane L.; Beaudet, Robert A.

    2016-05-01

    NASA policy restricts the total number of bacterial spores that can remain on a spacecraft traveling to any planetary body which might harbor life or have evidence of past life. Hydrazine, N2H4, is commonly used as a propellant on spacecraft. Hydrazine as a liquid is known to inactivate bacterial spores. We have now verified that hydrazine vapor also inactivates bacterial spores. After Bacillus atrophaeus ATCC 9372 spores deposited on stainless steel coupons were exposed to saturated hydrazine vapor in closed containers, the spores were recovered from the coupons, serially diluted, pour plated and the surviving bacterial colonies were counted. The exposure times required to reduce the spore population by a factor of ten, known as the D-value, were 4.70 ± 0.50 h at 25 °C and 2.85 ± 0.13 h at 35 °C. These inactivation rates are short enough to ensure that the bioburden of the surfaces and volumes would be negligible after prolonged exposure to hydrazine vapor. Thus, all the propellant tubing and internal tank surfaces exposed to hydrazine vapor do not contribute to the total spore count.

  6. Sodium Butyrate Induces Endoplasmic Reticulum Stress and Autophagy in Colorectal Cells: Implications for Apoptosis

    OpenAIRE

    Jintao Zhang; Man Yi; Longying Zha; Siqiang Chen; Zhijia Li; Cheng Li; Mingxing Gong; Hong Deng; Xinwei Chu; Jiehua Chen; Zheqing Zhang; Limei Mao; Suxia Sun

    2016-01-01

    Purpose Butyrate, a short-chain fatty acid derived from dietary fiber, inhibits proliferation and induces cell death in colorectal cancer cells. However, clinical trials have shown mixed results regarding the anti-tumor activities of butyrate. We have previously shown that sodium butyrate increases endoplasmic reticulum stress by altering intracellular calcium levels, a well-known autophagy trigger. Here, we investigated whether sodium butyrate-induced endoplasmic reticulum stress mediated au...

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

    Science.gov (United States)

    Jia, Yanglei; Xu, Gang; Zhou, Wenjing; Wang, Zhenzheng; Meng, Linlin; Zhou, Songnan; Xu, Xia; Yuan, Huiqing; Tian, Keli

    2014-01-01

    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.

  8. The natural product peiminine represses colorectal carcinoma tumor growth by inducing autophagic cell death

    Energy Technology Data Exchange (ETDEWEB)

    Lyu, Qing [School of Life Sciences, Tsinghua University, Beijing, 100084 (China); Key Lab in Healthy Science and Technology, Division of Life Science, Graduate School at Shenzhen, Tsinghua University, Shenzhen, 518055 (China); Tou, Fangfang [Jiangxi Provincial Key Lab of Oncology Translation Medicine, Jiangxi Cancer Hospital, Nanchang, 330029 (China); Su, Hong; Wu, Xiaoyong [First Affiliated Hospital, Guiyang College of Traditional Chinese Medicine, Guiyang, 550002 (China); Chen, Xinyi [Department of Hematology and Oncology, Beijing University of Chinese Medicine, Beijing, 100029 (China); Zheng, Zhi, E-mail: zheng_sheva@hotmail.com [Jiangxi Provincial Key Lab of Oncology Translation Medicine, Jiangxi Cancer Hospital, Nanchang, 330029 (China)

    2015-06-19

    Autophagy is evolutionarily conservative in eukaryotic cells that engulf cellular long-lived proteins and organelles, and it degrades the contents through fusion with lysosomes, via which the cell acquires recycled building blocks for the synthesis of new molecules. In this study, we revealed that peiminine induces cell death and enhances autophagic flux in colorectal carcinoma HCT-116 cells. We determined that peiminine enhances the autophagic flux by repressing the phosphorylation of mTOR through inhibiting upstream signals. Knocking down ATG5 greatly reduced the peiminine-induced cell death in wild-type HCT-116 cells, while treating Bax/Bak-deficient cells with peiminine resulted in significant cell death. In summary, our discoveries demonstrated that peiminine represses colorectal carcinoma cell proliferation and cell growth by inducing autophagic cell death. - Highlights: • Peiminine induces autophagy and upregulates autophagic flux. • Peiminine represses colorectal carcinoma tumor growth. • Peiminine induces autophagic cell death. • Peiminine represses mTOR phosphorylation by influencing PI3K/Akt and AMPK pathway.

  9. Expression and significance of PTEN, hypoxia-inducible factor-1 alpha in colorectal adenoma and adenocarcinoma

    Institute of Scientific and Technical Information of China (English)

    Ying-An Jiang; Li-Fang Fan; Chong-Qing Jiang; You-Yuan Zhang; He-Sheng Luo; Zhi-Jiao Tang; Dong Xia; Ming Wang

    2003-01-01

    AIM: To investigate the expression and significance of PTEN,hypoxia-inducible factor-1 alpha (HIF-1α), and targeting gene VEGF during colorectal carciogenesis.METHODS: Total 71 cases colorectal neoplasms (9 cases of colorectal adenoma and 62 colorectal adenocarcinoma)were formalin fixed and paraffin-embedded, and all specimens were evaluated for PTEN mRNA, HIF-1α mRNA and VEGF protein expression. PTEN mRNA, HIF-1α mRNA were detected by in situ hybridization. VEGF protein was identified by citrate-microwave SP immunohistochemical method.RESULTS: There were significant differences in PTEN, HIF1α and VEGF expression between colorectal adenomas and colorectal adenocarcinoma (P<0.05). The level of PTEN expression decreased as the pathologic stage increased.Conversely, HIF-1α and VEGF expression increased with the Dukes stage as follows: stage A (0.1029±0.0457:0.1207± 0.0436), stage B (0.1656±0.0329: 0.1572±0.0514),and stage C+D (0.2335±0.0748: 0.2219±0.0803). For PTEN expression, there was a significant difference among Dukes stage A, B, and C+D, and the level of PTEN expression was found to be significant higher in Dukes stage A or B than that of Dukes stage C or D. For HIF-1α expression,there was a significant difference between Dukes stage A and B, and the level of HIF-1α expression was found to be significantly higher in Dukes stage C+D than that of Dukes stage A or B. The VEGF expression had similar results as HIF-1α expression. In colorectal adenocarcinoma,decreased levels of PTEN were significantly associated with increased expression of HIF-1α mRNA (r=-0.36, P<0.05)and VEGF protein (r=-0.48, P<0.05) respectively. The levels of HIF-1 were positively correlated with VEGF expression (r=0.71, P<0.01).CONCLUSION: Loss of PTEN expression and increased levels of HIF-1α and VEGF may play an important role in carcinogenesis and progression of colorectal adenocarcinoma.

  10. Salinomycin induces apoptosis in cisplatin-resistant colorectal cancer cells by accumulation of reactive oxygen species.

    Science.gov (United States)

    Zhou, Jin; Li, Pu; Xue, Xiaofeng; He, Songbing; Kuang, Yuting; Zhao, Hong; Chen, Shaoji; Zhi, Qiaoming; Guo, Xiaobo

    2013-10-24

    Postoperative chemotherapy for Colorectal cancer (CRC) patients is not all effective and the main reason might lie in cancer stem cells (CSCs). Emerging studies showed that CSCs overexpress some drug-resistance related proteins, which efficiently transport the chemotherapeutics out of cancer cells. Salinomycin, which considered as a novel and an effective anticancer drug, is found to have the ability to kill both CSCs and therapy-resistant cancer cells. To explore the potential mechanisms that salinomycin could specifically target on therapy-resistant cancer cells in colorectal cancers, we firstly obtained cisplatin-resistant (Cisp-resistant) SW620 cells by repeated exposure to 5 μmol/l of cisplatin from an original colorectal cancer cell line. These Cisp-resistant SW620 cells, which maintained a relative quiescent state (G0/G1 arrest) and displayed stem-like signatures (up-regulations of Sox2, Oct4, Nanog, Klf4, Hes1, CD24, CD26, CD44, CD133, CD166, Lgr5, ALDH1A1 and ALDH1A3 mRNA expressions) (p 0.05), but could induce cell death process (p GSH-PX activities (p cisplatin-resistant colorectal cancer cells.

  11. Electrochemical Disposal of Hydrazines in Water

    Science.gov (United States)

    Kim, Jinseong; Gonzalez-Mar, Anuncia; Salinas, Carlos; Rutherford, Larris; Jeng, King-Tsai; Andrews, Craig; Yalamanchili, Ratlaya

    2007-01-01

    An electrochemical method of disposal of hydrazines dissolved in water has been devised. The method is applicable to hydrazine (N2H4), to monomethyl hydrazine [also denoted by MMH or by its chemical formula, (CH3)HNNH2], and to unsymmetrical dimethyl hydrazine [also denoted UDMH or by its chemical formula, (CH3)2NNH2]. The method involves a room-temperature process that converts the hydrazine to the harmless products N2, H2O, and, in some cases, CO2

  12. Metformin prevents DMH-induced colorectal cancer in diabetic rats by reversing the warburg effect.

    Science.gov (United States)

    Jia, Yanglei; Ma, Zengyi; Liu, Xiaofei; Zhou, Wenjing; He, Shan; Xu, Xia; Ren, Guijie; Xu, Gang; Tian, Keli

    2015-11-01

    Epidemiologic studies have shown that the treatment of diabetics with metformin reduced the risk of cancer-related mortality. Here, we investigated the chemopreventive effects of metformin on dimethylhydrazine (DMH)-induced colorectal carcinogenesis in diabetic SD rats following metformin treatment and the effect on Warburg effect involved in this process. Diabetic rat models were induced with high-fat feeding in combination with a low dose of Streptozotocin (STZ) and then induce colorectal cancer with a low dose of DMH. The formation of colorectal Aberrant crypt foci (ACF) and the incidence, number and size of the tumor were measured. The proliferation indices of colonic tissues were determined through Proliferating cell nuclear antigen (PCNA) immunostaining. Then detect the expression of PK and IDH in colonic tissues using immunohistochemistry and Western blot. The enzyme activities of HK and PDH in colonic tissues were measured. The growth and expression of PK and IDH and activity of HK and PDH in cell lines LoVo and HT-29 were measured after metformin treatment. The results showed that metformin treatment significantly inhibited the formation of ACF and tumors. The proliferation index of colonic tissues was significantly decreased following metformin treatment. In addition, metformin inhibited cell growth and decreased the imbalance in the expression of the enzymes involved in glycolysis and the TCA cycle. These findings suggested that metformin might produce a synergistic colon cancer-preventative effect in diabetic patients through the regulation of the enzymes expression involved in glucose metabolism.

  13. Occupational safety considerations with hydrazine

    Science.gov (United States)

    Clewell, Harvey J., III; Mcdougal, James N.; George, Marilyn E.; Andersen, Melvin E.

    1992-01-01

    Hydrazine is a reducing agent that is most commonly used as a propellant and as an oxygen scavenger in boilers. Hydrazine is extremely irritating and has been demonstrated to produce both acute and chronic toxicity. As a result, the established permissible inhalation exposure limits are very low, and respiration protection is required whenever vapors are present. Liquid hydrazine penetrates the skin and produces a chemical burn; therefore, some protective measures must also be taken to protect the skin from liquid contact. Often, however, a cumbersome, whole-body protective suit is worn to protect against skin contact with vapor as well. To what extent it is actually necessary to protect skin from vapor penetration had not previously been demonstrated. In an attempt to answer this question, we conducted a study with rats to compare the dermal penetration of hydrazine vapor with inhalation. Pharmacokinetic modeling was used to compare body burdens resulting from these different routes of exposure. The analysis concluded that the vapor concentration during a skin-only exposure would have to be at least 200 times higher than that during inhalation to achieve the same body burden. This type of estimation illustrates the use of predictive toxicology in occupational exposures.

  14. CCR5 blockage by maraviroc induces cytotoxic and apoptotic effects in colorectal cancer cells.

    Science.gov (United States)

    Pervaiz, Asim; Ansari, Shariq; Berger, Martin R; Adwan, Hassan

    2015-05-01

    Alterations in the expression of C-C chemokine receptor type 5 (CCR5 or CD195) have been correlated with disease progression in different cancers. Recently, a few investigations have reported the blockage of this receptor by an antagonist (maraviroc) and its antineoplastic effects on tumor cell growth. However, little is known about the mechanistic reasons behind these antineoplastic effects of CCR5 blockage by maraviroc. In this study, we blocked the CCR5 receptor by maraviroc in SW480 and SW620 colorectal cancer cells to study the resulting changes in biological properties and related pathways. This blockage induced significantly reduced proliferation and a profound arrest in G1 phase of the cell cycle. Concomitantly, maraviroc caused significant signs of apoptosis at morphological level. Significant modulation of multiple apoptosis-relevant genes was also noticed at mRNA levels. In addition, we found remarkable increases in cleaved caspases at protein level. These modulations led us to propose a signaling pathway for the observed apoptotic effects. In conclusion, blocking the CCR5 by maraviroc induces significant cytotoxic and apoptotic effects in colorectal cancer cells. Thus, maraviroc can be considered a model compound, which may foster the development of further CCR5 antagonists to be used for the treatment of colorectal cancer.

  15. [Efficacy of Elental on prevention for chemotherapy-induced oral mucositis in colorectal cancer patients].

    Science.gov (United States)

    Ogata, Yutaka; Takeuchi, Masaaki; Ishibashi, Nobuya; Kibe, Shirou; Takahashi, Kenjirou; Uchida, Shinji; Murakami, Naotaka; Yahara, Toshirou; Shirouzu, Kazuo

    2012-04-01

    The present study was designed to evaluate the preventive effects of elemental diet Elental (ED) on chemotherapy-induced stomatitis in patients with colorectal cancer. A total of 23 patients with colorectal cancer experiencing grade 1-3 stomatitis during treatment with chemotherapy (2- or 3-week per cycle) entered the current study. Their average age was 67 years, ranging from 44 to 84 years. A total of 22 patients received the same chemotherapy regimen, but also received more than 80 g of Elental (ED) (including 1, 932 mg of L-glutamine), per day. FOLFOX, FOLFIRI or XELOX-based chemotherapy was used. A dose reduction of 5-FU, capacitabine or S-1 was performed in 5 patients who experienced grade 2 or 3 stomatitis. The maximum grade of stomatitis decreased in 18 of the 22 patients after the first treatment course, and decreased in 20 of 22 patients after the second course with ED.The preventive efficacy of ED on stomatitis was noted in a dose-dependent manner.Similarly, the maximum grade of neutropenia decreased in 10 of 11 patients after their first or second treatment course with ED. We conclude that ED can significantly decrease the severity of chemotherapy-induced stomatitis in colorectal cancer patients in association with the control of neutropenia.

  16. Calvatia lilacina protein-extract induces apoptosis through glutathione depletion in human colorectal carcinoma cells.

    Science.gov (United States)

    Tsay, Jwu-Guh; Chung, King-Thom; Yeh, Chung-Hung; Chen, Wan-Ling; Chen, Chi-Hung; Lin, Martin Hsiu-Chu; Lu, Fung-Jou; Chiou, Jeng-Fong; Chen, Ching-Hsein

    2009-02-25

    This paper reports that a novel protein extract isolated from Calvatia lilacina (CL) can induce cell death against four types of human colorectal cancer cells. Importantly, CL was shown to be free of apoptotic effects against normal rat liver cells. We have also identified that CL-induced glutathione (GSH) depletion is the major contributor responsible for the apoptotic cell death induction of SW 480 cells, as evidenced by the observation that exogenously added N-acetylcysteine (NAC), or GSH, but not vitamin C, could offer a near complete protection of CL-treated cells against apoptotic cell death. Furthermore, the participation of reactive oxygen species (ROS) evoked a drop in the transmembrane potential (Delta Psi(m)) in the CL-induced apoptotic cell death. This observation can only be deemed as a minor pathway due to the fact that cyclosporine A (CyA) could only partially rescue the CL-treated cells from apoptotic cell death. Likewise, despite the fact that CL could induce the upregulation of Bax, its knockdown via siRNA (48 h) failed to completely mitigate apoptotic cell death, indicating that its role in this apoptotic process was insignificant. To further explore the possible underlying mechanism associated with CL-induced GSH depletion, we proceeded to determine the effect of CL on the cellular gamma-glutamylcysteine synthetase (gamma-GCS), a rate-limiting enzyme responsible for GSH biosynthesis, and demonstrated that indeed gamma-GCS could be repressed by CL. Taken together, we report here for the first time that the anticancer effect of CL on human colorectal cancer cells is mediated through GSH depletion mechanism rather than a ROS-mediated killing process. This functional attribute of CL can thus provide the basis for the strategic design of a treatment of colorectal cancer.

  17. Sodium Butyrate Induces Endoplasmic Reticulum Stress and Autophagy in Colorectal Cells: Implications for Apoptosis.

    Directory of Open Access Journals (Sweden)

    Jintao Zhang

    Full Text Available Butyrate, a short-chain fatty acid derived from dietary fiber, inhibits proliferation and induces cell death in colorectal cancer cells. However, clinical trials have shown mixed results regarding the anti-tumor activities of butyrate. We have previously shown that sodium butyrate increases endoplasmic reticulum stress by altering intracellular calcium levels, a well-known autophagy trigger. Here, we investigated whether sodium butyrate-induced endoplasmic reticulum stress mediated autophagy, and whether there was crosstalk between autophagy and the sodium butyrate-induced apoptotic response in human colorectal cancer cells.Human colorectal cancer cell lines (HCT-116 and HT-29 were treated with sodium butyrate at concentrations ranging from 0.5-5mM. Cell proliferation was assessed using MTT tetrazolium salt formation. Autophagy induction was confirmed through a combination of Western blotting for associated proteins, acridine orange staining for acidic vesicles, detection of autolysosomes (MDC staining, and electron microscopy. Apoptosis was quantified by flow cytometry using standard annexinV/propidium iodide staining and by assessing PARP-1 cleavage by Western blot.Sodium butyrate suppressed colorectal cancer cell proliferation, induced autophagy, and resulted in apoptotic cell death. The induction of autophagy was supported by the accumulation of acidic vesicular organelles and autolysosomes, and the expression of autophagy-associated proteins, including microtubule-associated protein II light chain 3 (LC3-II, beclin-1, and autophagocytosis-associated protein (Atg3. The autophagy inhibitors 3-methyladenine (3-MA and chloroquine inhibited sodium butyrate induced autophagy. Furthermore, sodium butyrate treatment markedly enhanced the expression of endoplasmic reticulum stress-associated proteins, including BIP, CHOP, PDI, and IRE-1a. When endoplasmic reticulum stress was inhibited by pharmacological (cycloheximide and mithramycin and genetic

  18. Active Hydrazine Vapor Sampler (AHVS)

    Science.gov (United States)

    Young, Rebecca C.; Mcbrearty, Charles F.; Curran, Daniel J.

    1993-01-01

    The Active Hydrazine Vapor Sampler (AHVS) was developed to detect vapors of hydrazine (HZ) and monomethylhydrazine (MMH) in air at parts-per-billion (ppb) concentration levels. The sampler consists of a commercial personal pump that draws ambient air through paper tape treated with vanillin (4-hydroxy-3-methoxybenzaldehyde). The paper tape is sandwiched in a thin cardboard housing inserted in one of the two specially designed holders to facilitate sampling. Contaminated air reacts with vanillin to develop a yellow color. The density of the color is proportional to the concentration of HZ or MMH. The AHVS can detect 10 ppb in less than 5 minutes. The sampler is easy to use, low cost, and intrinsically safe and contains no toxic material. It is most beneficial for use in locations with no laboratory capabilities for instrumentation calibration. This paper reviews the development, laboratory test, and field test of the device.

  19. The Oxidation of Hydrazine by Nitric Acid

    Energy Technology Data Exchange (ETDEWEB)

    Karraker, D.G.

    2001-07-02

    Hydrazine nitrate-nitric acid solutions are used in the ion exchange process for separating Pu-238 and Np-237 and have been found to dissolve plutonium metal in a manner advantageous to SRP metal recovery operations. Laboratory tests on the stability of hydrazine in nitric acid solutions were performed to obtain accurate data, and the results of these tests are reported here. These tests provide sufficient information to specify temperature control for hydrazine-nitric acid solutions in plant processes.

  20. Sodium butyrate induces DRP1-mediated mitochondrial fusion and apoptosis in human colorectal cancer cells

    OpenAIRE

    Tailor, Dhanir; Hahm, Eun-Ryeong; Kale, Raosaheb K.; Singh, Shivendra V.; Singh, Rana P.

    2013-01-01

    Sodium butyrate (NaBt) is the byproduct of anaerobic microbial fermentation inside the gastro-intestinal tract that could reach upto 20 mM, and has been shown to inhibit the growth of various cancers. Herein, we evaluated its effect on mitochondrial fusion and associated induction of apoptosis in colorectal cancer cells (CRC). NaBt treatment at physiological (1-5 mM) concentrations for 12 and 24 h decreased the cell viability and induced G2-M phase cell cycle arrest in HCT116 (12h) and SW480 ...

  1. Linoleic acid suppresses colorectal cancer cell growth by inducing oxidant stress and mitochondrial dysfunction

    Directory of Open Access Journals (Sweden)

    Shen Shengrong

    2010-09-01

    Full Text Available Abstract Some polyunsaturated fatty acids (PUFAs, if not all, have been shown to have tumoricidal action, but their exact mechanism(s of action is not clear. In the present study, we observed that n-6 PUFA linoleic acid (LA inhibited tumor cell growth at high concentrations (above 300 μM; while low concentrations (100-200 μM promoted proliferation. Analysis of cell mitochondrial membrane potential, reactive oxygen species (ROS formation, malondialdehyde (MDA accumulation and superoxide dismutase (SOD activity suggested that anti-cancer action of LA is due to enhanced ROS generation and decreased cell anti-oxidant capacity that resulted in mitochondrial damage. Of the three cell lines tested, semi-differentiated colorectal cancer cells RKO were most sensitive to the cytotoxic action of LA, followed by undifferentiated colorectal cancer cell line (LOVO while the normal human umbilical vein endothelial cells (HUVEC were the most resistant (the degree of sensitivity to LA is as follows: RKO > LOVO > HUVEC. LA induced cell death was primed by mitochondrial apoptotic pathway. Pre-incubation of cancer cells with 100 μM LA for 24 hr enhanced sensitivity of differentiated and semi-differentiated cells to the subsequent exposure to LA. The relative resistance of LOVO cells to the cytotoxic action of LA is due to a reduction in the activation of caspase-3. Thus, LA induced cancer cell apoptosis by enhancing cellular oxidant status and inducing mitochondrial dysfunction.

  2. Prognostic value of Annexin A3 in human colorectal cancer and its correlation with hypoxia-inducible factor-1α

    Science.gov (United States)

    Xie, Yong-Qiu; Fu, DI; He, Zheng-Hua; Tan, Qing-Dong

    2013-12-01

    Annexins are a family of intracellular proteins that bind membrane phospholipids in a Ca(2+) concentration-dependent manner and are involved in cellular processes, including apoptosis, proliferation and differentiation. Hypoxia-inducible factor-1α (HIF-1α) has been hypothesized to be critical in the angiogenesis of tumors. We hypothesized that Annexin A3, a member of the Annexin family, and HIF-1α may be associated with each other in colorectal cancer. The expression of Annexin A3 and HIF-1α in 60 colorectal cancer tissues was assessed by immunohistochemistry to statistically analyze the association between the clinicopathological features and survival of these cases. In the present study, 65 and 47% of colorectal cancer specimens were found to show Annexin A3 and HIF-1α immunoreactivity, respectively. Annexin A3 expression was found to significantly correlate with tumor size and Dukes' stage (all PA3 and HIF-1α protein expression exhibited a similar pattern in these samples, and their expression was found to correlate with poor survival in colorectal cancer patients. The results of the current study indicated for the first time that the increased expression of Annexin A3 in colorectal cancer correlates significantly with tumor growth and poor prognosis. Furthermore, Annexin A3 has been found to correlate with HIF-1α expression. These observations highlight an improved understanding of the carcinogenesis of colorectal cancer.

  3. Early diagnosis of colorectal cancer in rats with DMH induced carcinogenesis by means of urine autofluorescence analysis.

    Science.gov (United States)

    Šteffeková, Zuzana; Birková, Anna; Bomba, Alojz; Mareková, Mária

    2014-01-01

    Cancer is one of the most highlighted topics of current research. Early detection of this disease allows more effective therapy, hence higher chance of cure. Application of fluorescence spectral techniques into oncological diagnostic is one of the potential alternatives. Chemically induced carcinogenesis in rats is widely used model for exploration of various aspects of colorectal cancer. This study shows value of discriminate analysis of urine fluorescent fingerprint between healthy control group of rats and those with dimethylhydrazine induced early lesions of colorectal cancer. Using fluorescence spectroscopy, significant difference (P < 0.05) between both of group was achieved.

  4. Sorbitol induces apoptosis of human colorectal cancer cells via p38 MAPK signal transduction.

    Science.gov (United States)

    Lu, Xue; Li, Chun; Wang, Yong-Kun; Jiang, Kun; Gai, Xiao-Dong

    2014-06-01

    Sorbitol has been reported to have anticancer effects in several tumor models, however its effects on colorectal cancer remain elusive. In the present study, the effects of sorbitol on growth inhibition and apoptosis in the colorectal cancer HCT116 cell line were evaluated and its mechanism of action was examined. An MTT assay was utilized to determine the effect of sorbitol on HCT116 cell proliferation at different time points and variable doses. Western blot analysis was used to examine the effect of sorbitol on apoptosis-related protein expression and the p38 MAPK signaling pathway. The results revealed that sorbitol may inhibit the growth of HCT116 cells in a time- and dose-dependent manner. Following treatment with sorbitol for 3 h, western blotting demonstrated cleavage of the caspase-3 zymogen protein and a cleavage product of poly (ADP-ribose) polymerase (PARP), a known substrate of caspase-3, was also evident. During sorbitol-induced apoptosis, the mitochondrial pathway was activated by a dose-dependent increase in Bax expression and cytochrome c release, while the expression of anti-apoptotic protein Bcl-2 was significantly decreased in a dose-dependent manner. The investigation for the downstream signal pathway revealed that sorbitol-induced apoptosis was mediated by an increase in phosphorylated p38 MAPK expression. Overall, the observations from the present study imply that sorbitol causes increased levels of Bax in response to p38 MAPK signaling, which results in the initiation of the mitochondrial death cascade. Therefore, sorbitol is a promising candidate as a potential chemotherapeutic agent for the treatment of colorectal cancer HCT116 cells.

  5. Role of MCP-1 in alcohol-induced aggressiveness of colorectal cancer cells.

    Science.gov (United States)

    Xu, Mei; Wang, Siying; Qi, Yuanlin; Chen, Li; Frank, Jacqueline A; Yang, Xiuwei H; Zhang, Zhuo; Shi, Xianglin; Luo, Jia

    2016-05-01

    Epidemiological studies demonstrate that alcohol consumption is associated with an increased risk of colorectal cancer (CRC). In addition to promoting carcinogenesis, alcohol may also accelerate the progression of existing CRC. We hypothesized that alcohol may enhance the aggressiveness of CRC. In this study, we investigated the effect of alcohol on the migration/invasion and metastasis of CRC. Alcohol increased the migration/invasion of colorectal cancer cells (DLD1, HCT116, HT29, and SW480) in a concentration-dependent manner. Among these colon cancer cell lines, HCT116 cells were most responsive while HT29 cells were the least responsive to ethanol-stimulated cell migration/invasion. These in vitro results were supported by animal studies which demonstrated that ethanol enhanced the metastasis of colorectal cancer cells to the liver and lung. Monocyte chemoattractant protein-1 (MCP-1) is a chemokine that plays an important role in regulating tumor microenvironment and metastasis. Alcohol increased the expression of MCP-1 and its receptor CCR2 at both protein and mRNA levels. The pattern of alcohol-induced alterations in MCP-1 expression was consistent with its effect on migration/invasion; HCT116 cells displayed the highest up-regulation of MCP-1/CCR2 in response to alcohol exposure. An antagonist of CCR2 blocked alcohol-stimulated migration. Alcohol caused an initial cytosolic accumulation of β-catenin and its subsequent nuclear translocation by inhibiting GSK3β activity. Alcohol stimulated the activity of MCP-1 gene promoter in a β-catenin-dependent manner. Furthermore, knock-down of MCP-1/CCR2 or β-catenin was sufficient to inhibit alcohol-induced cell migration/invasion. Together, these results suggested that alcohol may promote the metastasis of CRC through modulating GSK3β/β-catenin/MCP-1 pathway. © 2015 Wiley Periodicals, Inc.

  6. Anisomycin-induced GATA-6 degradation accompanying a decrease of proliferation of colorectal cancer cell

    Energy Technology Data Exchange (ETDEWEB)

    Ushijima, Hironori; Horyozaki, Akiko; Maeda, Masatomo, E-mail: mmaeda@nupals.ac.jp

    2016-09-09

    Transcription factor GATA-6 plays a key role in normal cell differentiation of the mesoderm and endoderm. On the other hand, GATA-6 is abnormally overexpressed in many clinical gastrointestinal cancer tissue samples, and accelerates cell proliferation or an anti-apoptotic response in cancerous tissues. We previously showed that activation of the JNK signaling cascade causes proteolysis of GATA-6. In this study, we demonstrated that anisomycin, a JNK activator, stimulates nuclear export of GATA-6 in a colorectal cancer cell line, DLD-1. Concomitantly, anisomycin remarkably inhibits the proliferation of DLD-1 cells via G2/M arrest in a plate culture. However, it did not induce apoptosis under growth arrest conditions. Furthermore, the growth of DLD-1 cells in a spheroid culture was suppressed by anisomycin. Although 5-FU showed only a slight inhibitory effect on 3D spheroid cultures, the same concentration of 5-FU together with a low concentration of anisomycin exhibited strong growth inhibition. These results suggest that the induction of GATA-6 dysfunction may be more effective for chemotherapy for colorectal cancer, although the mechanism underlying the synergistic effect of 5-FU and anisomycin remains unknown. - Highlights: • Anisomycin induces proteolysis of GATA-6 in DLD-1 cells. • Anisomycin remarkably inhibits the proliferation of DLD-1 cells via G2/M arrest. • Anisomycin suppresses the growth of spheroids of DLD-1, and enhances the effect of 5-FU.

  7. Metformin enhances TRAIL-induced apoptosis by Mcl-1 degradation via Mule in colorectal cancer cells

    Science.gov (United States)

    Kim, Jung Lim; Kim, Bo Ram; Na, Yoo Jin; Jo, Min Jee; Jeong, Yoon A.; Lee, Suk-Young; Lee, Sun Il; Lee, Yong Yook; Oh, Sang Cheul

    2016-01-01

    Metformin is an anti-diabetic drug with a promising anti-cancer potential. In this study, we show that subtoxic doses of metformin effectively sensitize human colorectal cancer (CRC) cells to tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL), which induces apoptosis. Metformin alone did not induce apoptosis, but significantly potentiated TRAIL-induced apoptosis in CRC cells. CRC cells treated with metformin and TRAIL showed activation of the intrinsic and extrinsic pathways of caspase activation. We attempted to elucidate the underlying mechanism, and found that metformin significantly reduced the protein levels of myeloid cell leukemia 1 (Mcl-1) in CRC cells and, the overexpression of Mcl-1 inhibited cell death induced by metformin and/or TRAIL. Further experiments revealed that metformin did not affect mRNA levels, but increased proteasomal degradation and protein stability of Mcl-1. Knockdown of Mule triggered a significant decrease of Mcl-1 polyubiquitination. Metformin caused the dissociation of Noxa from Mcl-1, which allowed the binding of the BH3-containing ubiquitin ligase Mule followed by Mcl-1ubiquitination and degradation. The metformin-induced degradation of Mcl-1 required E3 ligase Mule, which is responsible for the polyubiquitination of Mcl-1. Our study is the first report indicating that metformin enhances TRAIL-induced apoptosis through Noxa and favors the interaction between Mcl-1 and Mule, which consequently affects Mcl-1 ubiquitination. PMID:27517746

  8. Roscovitine synergizes with conventional chemo-therapeutic drugs to induce efficient apoptosis of human colorectal cancer cells

    Institute of Scientific and Technical Information of China (English)

    Mohamed Salah I Abaza; Abdul-Majeed A Bahman; Rajaa J Al-Attiyah

    2008-01-01

    AIM:To examine the ability of cyclin-dependent kinase inhibitor(CDKI)roscovitine(Rosco)to enhance the antitumor effects of conventional chemotherapeutic agents acting by different mechanisms against human colorectal cancer.METHODS:Human colorectal cancer cells were treated,individually and in combination,with Rosco,taxol,5-Fluorouracil(S-FU),doxorubicine or vinblastine.The antiproliferative effects and the type of interaction of Rosco with tested chemotherapeutic drugs were determined.Cell cycle alterations were investigated by fluorescence-activated cell sorter FACS analysis.Apoptosis was determined by DNA fragmentation assay.RESULTS:Rosco inhibited the proliferation of tumor cells in a time- and dose-dependent manner.The efficacies of all tested chemotherapeutic drugs were markedly enhanced 3.0-8.42×103 and 130-5.28×103 fold in combination with 5 and 10 μg/mL Rosco,re-spectively.The combinatiou of Rosco and chemotherapeutic drugs inhibited the growth of human colorectal cancer cells in an additive or synergistic fashion,and in a time and dose dependent manner.Rosco induced apoptosis and synergized with tested chemotherapeutic drugs to induce efficient apoptosis in human colorectal cancer cells.Sequential,inverted sequential and simultaneous treatment of cancer cells with combinations of chemotherapeutic drugs and Rosco arrested the growth of human colorectal cancer cells at various phases of the cell cycle as follows:Taxol/Rosco(G2/M-and S-phases),5-FU/Rosco(S-phase),Dox/Rosco(S-phase)and Vinb/Rosco(G2/M-and S-phases).CONCLUSION:Since the efficacy of many anticancer drugs depends on their ability to induce apoptotic cell death,modulation of this parameter by Cell cycle inhibitors may provide a novel chemo-preventive and chemothempeutic strategy for human colorectal cancer.(C)2008 The WJG Press.All rights reserved.

  9. Beef meat promotion of dimethylhydrazine-induced colorectal carcinogenesis biomarkers is suppressed by dietary calcium.

    Science.gov (United States)

    Pierre, Fabrice; Santarelli, Raphaëlle; Taché, Sylviane; Guéraud, Françoise; Corpet, Denis E

    2008-05-01

    Red meat consumption is associated with increased risk of colorectal cancer. We have previously shown that haemin, Hb and red meat promote carcinogen-induced preneoplastic lesions: aberrant crypt foci (ACF) and mucin-depleted foci (MDF) in rats. We have also shown that dietary Ca, antioxidant mix and olive oil inhibit haemin-induced ACF promotion, and normalize faecal lipoperoxides and cytotoxicity. Here we tested if these strategies are effective also against red meat promotion in dimethylhydrazine-induced rats. Three diets with 60 % beef meat were supplemented with calcium phosphate (31 g/kg), antioxidant agents (rutin and butylated hydroxyanisole, 0.05 % each) and olive oil (5 %). ACF, MDF, faecal water cytotoxicity, thiobarbituric acid reactive substances (TBARS) and urinary 1,4-dihydroxynonane mercapturic acid (DHN-MA) were measured. Beef meat diet increased the number of ACF (+30 %) and MDF (+100 %) (P Promotion was associated with increased faecal water TBARs ( x 4) and cytotoxicity ( x 2), and urinary DHN-MA excretion ( x 15). Ca fully inhibited beef meat-induced ACF and MDF promotion, and normalized faecal TBARS and cytotoxicity, but did not reduce urinary DHN-MA. Unexpectedly, high-calcium control diet-fed rats had more MDF and ACF in the colon than low-Ca control diet-fed rats. Antioxidant mix and olive oil did not normalize beef meat promotion nor biochemical factors. The results confirm that haem causes promotion of colon carcinogenesis by red meat. They suggest that Ca can reduce colorectal cancer risk in meat-eaters. The results support the concept that toxicity associated with the excess of a useful nutrient may be prevented by another nutrient.

  10. DNA repair by MGMT, but not AAG, causes a threshold in alkylation-induced colorectal carcinogenesis.

    Science.gov (United States)

    Fahrer, Jörg; Frisch, Janina; Nagel, Georg; Kraus, Alexander; Dörsam, Bastian; Thomas, Adam D; Reißig, Sonja; Waisman, Ari; Kaina, Bernd

    2015-10-01

    Epidemiological studies indicate that N-nitroso compounds (NOC) are causally linked to colorectal cancer (CRC). NOC induce DNA alkylations, including O (6)-methylguanine (O (6)-MeG) and N-methylated purines, which are repaired by O (6)-MeG-DNA methyltransferase (MGMT) and N-alkyladenine-DNA glycosylase (AAG)-initiated base excision repair, respectively. In view of recent evidence of nonlinear mutagenicity for NOC-like compounds, the question arises as to the existence of threshold doses in CRC formation. Here, we set out to determine the impact of DNA repair on the dose-response of alkylation-induced CRC. DNA repair proficient (WT) and deficient (Mgmt (-/-), Aag (-/-) and Mgmt (-/-)/Aag (-/-)) mice were treated with azoxymethane (AOM) and dextran sodium sulfate to trigger CRC. Tumors were quantified by non-invasive mini-endoscopy. A non-linear increase in CRC formation was observed in WT and Aag (-/-) mice. In contrast, a linear dose-dependent increase in tumor frequency was found in Mgmt (-/-) and Mgmt (-/-)/Aag (-/-) mice. The data were corroborated by hockey stick modeling, yielding similar carcinogenic thresholds for WT and Aag (-/-) and no threshold for MGMT lacking mice. O (6)-MeG levels and depletion of MGMT correlated well with the observed dose-response in CRC formation. AOM induced dose-dependently DNA double-strand breaks in colon crypts including Lgr5-positive colon stem cells, which coincided with ATR-Chk1-p53 signaling. Intriguingly, Mgmt (-/-) mice displayed significantly enhanced levels of γ-H2AX, suggesting the usefulness of γ-H2AX as an early genotoxicity marker in the colorectum. This study demonstrates for the first time a non-linear dose-response for alkylation-induced colorectal carcinogenesis and reveals DNA repair by MGMT, but not AAG, as a key node in determining a carcinogenic threshold.

  11. Dietary cholesterol promotes AOM-induced colorectal cancer through activating the NLRP3 inflammasome.

    Science.gov (United States)

    Du, Qianming; Wang, Qing; Fan, Huimin; Wang, Jianing; Liu, Xiuting; Wang, Hong; Wang, Yajing; Hu, Rong

    2016-04-01

    Prolonged ingestion of a cholesterol-enriched diet induces chronic, auto-inflammatory responses resulting in significant health problems including colorectal cancer. Inflammasomes are thought to mediate intestinal homeostasis, and their dysregulation contributes to inflammatory bowel diseases and colitis-associated cancer (CAC). However, in vitro and in vivo information regarding the inflammation-inducing and tumor-promoting effect of cholesterol is lacking. Here we show that the cholesterol promoted colon carcinogenesis in azoxymethane (AOM)-treated mice through activating the NLRP3 inflammasome. High cholesterol diet (HCD) significantly increased inflammatory responses and tumor burden. Cholesterol crystals, detected in the colon of mice fed with HCD, also promoted NLRP3 inflammasome activation in macrophages, as indicated by elevated expression of cleaved caspase-1, formation of NLRP3-ASC-caspase-1 complex assembly, and higher IL-1β secretion. Importantly, cholesterol was found to inhibit the activity of AMPKα in macrophages, leading to a significant production of mitochondrial ROS, which in turn activated the NLRP3 inflammasome. Moreover, crystal uptake and cathepsin B accounted for cholesterol crystal-induced inactivation of AMPKα. Finally, HCD-induced increase in IL-1β secretion, macrophage infiltration and tumor burden was diminished by the deletion of NLRP3 in AOM-treated mice. Taken together, our findings demonstrate that the pro-inflammatory and cancer-promoting effects of HCD are mediated by the activation of NLRP3 inflammasome. Our study extended our knowledge on how dietary choices can influence processes involved in chronic inflammatory disorders and colorectal cancer.

  12. Lifestyle related factors in the self management of chemotherapy induced peripheral neuropathy in colorectal cancer: : A systematic review

    NARCIS (Netherlands)

    Derksen, T.; Bours, M.J.; Mols, F.; Weijenberg, M.P.

    2017-01-01

    Background. Chemotherapy-induced peripheral neuropathy (CIPN) is a common adverse effect of chemotherapy treatment in colorectal cancer (CRC), negatively affecting the daily functioning and quality of life of CRC patients. Currently, there are no established treatments to prevent or reduce CIPN. The

  13. Lifestyle related factors in the self management of chemotherapy induced peripheral neuropathy in colorectal cancer: : A systematic review

    NARCIS (Netherlands)

    Derksen, T.; Bours, M.J.; Mols, F.; Weijenberg, M.P.

    2017-01-01

    Background. Chemotherapy-induced peripheral neuropathy (CIPN) is a common adverse effect of chemotherapy treatment in colorectal cancer (CRC), negatively affecting the daily functioning and quality of life of CRC patients. Currently, there are no established treatments to prevent or reduce CIPN. The

  14. Effect of dietary galacto-oligosaccharides on azoxymethane-induced aberrant crypt foci and colorectal cancer in Fischer 344 rats

    NARCIS (Netherlands)

    Wijnands, M.V.W.; Schoterman, H.C.; Bruijntjes, J.P.; Hollanders, V.M.H.; Woutersen, R.A.

    2001-01-01

    The aim of the present study was to investigate the effects of galacto-oligosaccharides (GOS, Elix'or) on the development of aberrant crypt foci (ACF) and colorectal tumours in rats treated with azoxymethane (AOM). Two groups of 102 male Fischer 344 rats were injected twice with AOM to induce colore

  15. THE APOPTOSIS OF EXPERIMENTAL COLORECTAL CARCINOMA CELLS INDUCED BY PEPTIDOGLYCAN OF BIFIDOBACTERIUM AND THE EXPRESSION OF APOPTOTIC REGULATING GENES

    Institute of Scientific and Technical Information of China (English)

    WANG Li-sheng; PAN Ling-jia; SHI Li; SUN Yong; ZHANG Ya-li; ZHOU Dian-yuan

    1999-01-01

    Objective: To explore the antitumor mechanisms of whole peptidoglycan of bifidobacterium. Methods: The apoptotic cells and the positive expression of bcl-2 and bax oncoprotein were studied nude mice transplantation tumors of colorectal carcinoma by employing in situ end labeling technique and immunohistochemical staining. Results:The apoptotic cell density, the positive rate and the staining intensity of bax oncoprotein of the transplantation tumor of colorectal carcinoma in the whole peptidoglycan injection group were significantly higher when compared with the tumor control group. The positive rate of bcl-2 oncoprotein in the whole peptidoglycan injection group was obviously lower than that in the tumor control group (P<0.01).Conclusion: Whole peptidoglycan of Bifidobacterium bifidum could induce cell apoptosis of nude mice transplantation tumors of colorectal carcinoma by downregulating the expression of the bcl-2 gene and upregulating the expression of the bax gene.

  16. RAGE mediates S100A4-induced cell motility via MAPK/ERK and hypoxia signaling and is a prognostic biomarker for human colorectal cancer metastasis

    Science.gov (United States)

    Dahlmann, Mathias; Okhrimenko, Anna; Marcinkowski, Patrick; Osterland, Marc; Herrmann, Pia; Smith, Janice; Heizmann, Claus W.; Schlag, Peter M.; Stein, Ulrike

    2014-01-01

    Survival of colorectal cancer patients is strongly dependent on development of distant metastases. S100A4 is a prognostic biomarker and inducer for colorectal cancer metastasis. Besides exerting intracellular functions, S100A4 is secreted extracellularly. The receptor for advanced glycation end products (RAGE) is one of its interaction partners. The impact of the S100A4-RAGE interaction for cell motility and metastasis formation in colorectal cancer has not been elucidated so far. Here we demonstrate the RAGE-dependent increase in migratory and invasive capabilities of colorectal cancer cells via binding to extracellular S100A4. We show the direct interaction of S100A4 and RAGE, leading to hyperactivated MAPK/ERK and hypoxia signaling. The S100A4-RAGE axis increased cell migration (PRAGE and RAGE-specific antibodies. In colorectal cancer patients, not distantly metastasized at surgery, high RAGE expression in primary tumors correlated with metachronous metastasis, reduced overall (P=0.022) and metastasis-free survival (P=0.021). In summary, interaction of S100A4-RAGE mediates S100A4-induced colorectal cancer cell motility. RAGE by itself represents a biomarker for prognosis of colorectal cancer. Thus, therapeutic approaches targeting RAGE or intervening in S100A4-RAGE-dependent signaling early in tumor progression might represent alternative strategies restricting S100A4-induced colorectal cancer metastasis. PMID:24952599

  17. Lobaplatin suppresses proliferation and induces apoptosis in the human colorectal carcinoma cell Line LOVO in vitro.

    Science.gov (United States)

    Dai, Hong-yu; Liu, Lin; Qin, Shu-kui; He, Xiang-ming; Li, Su-yi

    2011-06-01

    Lobaplatin, as the third-generation platinum antineoplastic agent, showed promising antineoplastic effects in variety of preclinical test tumor models. We investigated the inhibition effect of lobaplatin on the colorectal carcinoma cell line LOVO in vitro, and explored its mechanism of action. The MTT assay was used to determine the inhibitory effect and inhibition ratio of lobaplatin on LOVO at various lobaplatin concentrations (500 μM, 1000 μM, 2000 μM). Apoptosis was detected by terminal deoxynucleotide transferase-mediated dUTP nickend labelling (TUNEL). The cell cycle and apoptotic rate were analyzed by flow cytometry (FCM) and the expression of caspase-3,8,9 in cells was detected by chromometry. The results of MTT assay showed that proliferation of LOVO cells was inhibited by lobaplatin in a concentration-dependent manner. Apoptosis was detected in LOVO cells by TUNEL. The FCM assay indicated that lobaplatin altered the cell cycle and induced apoptosis of the LOVO cells when treated for 24h, the percentages of cells in the S phase transition were increased, whereas the percentages of cells in the G(2) transition were decreased. The expressions of caspase-389 is higher than the control group after LOVO cells were treated by lobaplatin. Lobaplatin can inhibit the proliferation of colorectal carcinoma cell line LOVO by inducing apoptosis in vitro. The mechanism may be related to the "S" cycle arrest in cell cycle distribution and the up-regulated expression of caspase-8 and caspase-9 which up-regulated the expression of caspase-3.

  18. The hypoxia-mimetic agent CoCl₂ induces chemotherapy resistance in LOVO colorectal cancer cells.

    Science.gov (United States)

    Yang, Guanglei; Xu, Shuqing; Peng, Lintao; Li, Hui; Zhao, Yan; Hu, Yanfang

    2016-03-01

    Hypoxia, which is an important factor that mediates tumor progression and poor treatment response, is particularly associated with tumor chemoresistance. However, the molecular mechanisms underlying hypoxia-induced colorectal cancer chemoresistance remain unclear. The present study aimed to explore the mechanism underlying hypoxia‑induced chemotherapy resistance in LOVO colorectal cancer cells. LOVO cells were cultured in a hypoxic environment simulated by cobalt chloride (CoCl2), which is a chemical inducer of hypoxia‑inducible factor‑1α (HIF‑1α). HIF‑1α is a transcription factor that has an important role in tumor cell adaptation to hypoxia, and controls the expression of several genes. Various CoCl2 concentrations are often used to simulate degrees of hypoxia. In the present study, following treatment with CoCl2, an MTT assay was conducted to determine the growth and drug sensitivity of LOVO cells. Reverse transcription‑polymerase chain reaction and western blotting were used to detect the mRNA and protein expression levels of HIF‑1α and factors associated with chemotherapy resistance, including multidrug resistance protein (MRP) and multidrug resistant 1 (MDR1), which encodes the major transmembrane efflux transporter P‑glycoprotein (P‑gp). In addition, the expression levels of apoptosis‑related proteins, including B‑cell lymphoma 2 (Bcl‑2), Bcl‑2‑associated X protein (Bax) and Bcl‑2‑associated agonist of cell death (Bad) were detected by western blotting. Flow cytometry (FCM) was used to visually observe Adriamycin (ADR) accumulation and retention, thus analyzing intracellular drug transportation in cells under hypoxic and normoxic conditions. CoCl2‑simulated hypoxia was able to inhibit tumor cell proliferation, and upregulate the expression levels of HIF‑1α, MDR1/P‑gp and MRP. In addition, proapoptotic members of the Bcl‑2 protein family, Bax and Bad, were downregulated. The anti‑apoptotic member Bcl‑2

  19. Mars to orbit with pumped hydrazine

    Energy Technology Data Exchange (ETDEWEB)

    Whitehead, J C

    1999-04-27

    A propulsion point design is presented for lifting geological samples from Mars. Vehicle complexity is kept low by choosing a monopropellant single stage. Little new development is needed, as miniature pump fed hydrazine has been demonstrated. Loading the propellant just prior to operation avoids structural, thermal, and safety constraints otherwise imposed by earlier mission phases. Hardware mass and engineering effort are thereby diminished. The Mars liftoff mass is 7/8 hydrazine, <5% propulsion hardware, and >3% each for the payload and guidance.

  20. Occupational safety considerations with hydrazine fuels

    Science.gov (United States)

    Clewell, H. J.; Haddad, T. S.; George, M. E.; Mcdougal, J. N.; Andersen, M. E.

    1992-01-01

    A simple pharmacokinetic model and a specially designed dermal vapor exposure chamber which provides respiratory protection were used to determine the rate of penetration of hydrazine and 1,1-dimethylhydrazine (UDMH) vapor through the skin of rats. Parameters for the pharmacokinetic model were determined from intravenous and inhalation exposure data. The model was then used to estimate the skin permeation coefficient for hydrazine or UDMH vapor from the dermal-vapor exposure data. This analysis indicates that UDMH vapor has a relatively high permeability through skin (0.7 cm/hr), a value somewhat higher than was obtained for hydrazine by the same procedure (0.09 cm/hr). Based on these skin permeability results, a skin-only vapor exposure limit giving protection equivalent to the inhalation Threshold Limit Value (TLV) could be calculated. The current TLV's for UDMH and hydrazine are 0.5 and 0.1 ppm, respectively. The corresponding skin-only TLV equivalents, for personnel wearing respiratory protection, are 32 ppm for UDMH and 48 ppm for hydrazine. Should the proposed lowering to the TLV's for these compounds to 0.01 ppm be adopted, the equivalent skin-only TLV's would become 0.64 ppm for UDMH and 4.8 for hydrazine.

  1. Destruction of Hydrazine and Corrosion Monitoring

    Energy Technology Data Exchange (ETDEWEB)

    Won, H. J.; Park, S. Y.; Kim, S. B.; Jung, J. Y.; Choi, W. K.; Moon, J. K. [KAERI, Daejeon (Korea, Republic of)

    2016-05-15

    KAERI The agent uses Cu ion and hydrazine in an inorganic acid solution. This agent is used for the dissolution of Fe and Ni ions in a spinel type nickel chromium ferrite. After decontamination, the generation of the secondary waste can be reduced by the destruction of hydrazine. Wellman et al. reported that hydrazine is decomposed to water and nitrogen by hydrogen peroxide in the presence of Cu{sup 2+} ion. N{sub 2}H{sub 4}+2H{sub 2}0{sub 2} (Cu{sup 2+} →) N{sub 2} +4H{sub 2}0 As the decrease of the hydrazine concentration, the solution pH also becomes to decrease. The decrease of solution pH can affect the integrity of structural metal. The objective of the study is to investigate the decomposition characteristics of hydrazine by hydrogen peroxide. The corrosion compatibility of metal after the decomposition of hydrazine is also investigated. The application of a decontamination solution to the primary coolant system before decommissioning is necessary to minimize the personnel dose rates. In foreign countries, system decontaminations have been performed several times by applying the dilute organic chemical decontamination process. To prepare against the decommissioning of the nuclear power plant, it is necessary to develop the unique domestic chemical decontamination process.

  2. Visfatin is involved in promotion of colorectal carcinoma malignancy through an inducing EMT mechanism.

    Science.gov (United States)

    Yang, Jing; Zhang, Kun; Song, Haixing; Wu, Mingbo; Li, Jingyi; Yong, Ziyi; Jiang, Sheng; Kuang, Xi; Zhang, Tao

    2016-05-31

    Increasing evidences suggested visfatin, a newly discovered obesity-induced adipocytokine, is involved in promotion of cancer malignancy and correlated with worse clinical prognosis. While its effects and mechanisms on progression of colorectal cancer (CRC) remain unclear. Our clinical data show that visfatin protein is over expressed, positive associated with lymph node metastasis, high-grade tumor, and poor prognosis in 87 CRC patients. The levels of plasma visfatin are significantly upregulated in Stage IV colon cancer. Visfatin can significantly promote the in vitro migration and invasion of CRC cells via induction epithelial mesenchymal transition (EMT). It can increase the expression and nuclear translocation of Snail, a key transcription factor in regulating EMT. While silencing of Snail attenuates visfatin induced EMT. Further studies reveal visfatin can inhibit the association of Snail with GSK-3β and subsequently suppress ubiquitylation of Snail. In addition, visfatin can increase the expression and nuclear translocation of β-catenin, elevate its binding with Snail promoter, and then increase the transcription of Snail. While inhibitor of PI3K/Akt, LY294002, abolishes visfatin induced up regulation of Snail, Vimentin (Vim), β-catenin, and phosphorylated GSK-3β. In summary, our data suggest that increased expression of visfatin are associated with a more aggressive phenotype of CRC patients. It can trigger the EMT of CRC cells via Akt/GSK-3β/β-catenin signals.

  3. Acupuncture inhibition on neuronal activity of spinal dorsal horn induced by noxious colorectal distention in rat

    Institute of Scientific and Technical Information of China (English)

    Pei-Jing Rong; Bing Zhu; Qi-Fu Huang; Xin-Yan Gao; Hui Ben; Yan-Hua Li

    2005-01-01

    AIM: To observe how acupuncture stimulation influences the visceral nociception in rat and to clarify the interactions between acupuncture or somatic input and visceral nociceptive inputs in the spinal dorsal horn. These will provide scientific base for illustrating the mechanism of acupuncture on visceral pain.METHODS: Experiments were performed on SpragueDawley rats and the visceral nociceptive stimulus was generated by colorectal distention (CRD). Unit discharges from individual single neuron were recorded extracellularly with glass-microelectrode in L1-3 spinal dorsal horn.Acupuncture stimulation was applied at contralateral heterotopic acupoint and ipsilateral homotopic acupoint,both of which were innervated by the same segments that innervate also the colorectal-gut.RESULTS: The visceral nociception could be inhibited at the spinal level by the heterotopic somatic mechanical stimulation and acupuncture. The maximal inhibition was induced by acupuncture or the somatic noxious stimulation at spinal dorsal horn level with inhibiting rate of 68.61%and 60.79%, respectively (P<0.01 and <0.001). In reversible spinalized rats (cervical-thoracic cold block)both spontaneous activity and responses to CRD increased significantly in 16/20 units examined, indicating the existence of tonic descending inhibition. The inhibition of acupuncture on the noxious CRD disappeared totally in the reversible spinalized rats (P<0.001).CONCLUSION: The inputs of noxious CRD and acupuncture may interact at the spinal level. The nociceptive visceral inputs could be inhibited by acupuncture applied to hetero-topic acupoint. The effect indicates that the spinal dorsal horn plays a significant role in mediating the inhibition of acupuncture and somatic stimulation on the neuronal response to the noxious visceral stimulation and the inhibition is modulated by upper cervical cord and/or supra-spinal center.

  4. Obesity-Induced Colorectal Cancer Is Driven by Caloric Silencing of the Guanylin-GUCY2C Paracrine Signaling Axis.

    Science.gov (United States)

    Lin, Jieru E; Colon-Gonzalez, Francheska; Blomain, Erik; Kim, Gilbert W; Aing, Amanda; Stoecker, Brian; Rock, Justin; Snook, Adam E; Zhan, Tingting; Hyslop, Terry M; Tomczak, Michal; Blumberg, Richard S; Waldman, Scott A

    2016-01-15

    Obesity is a well-known risk factor for colorectal cancer but precisely how it influences risks of malignancy remains unclear. During colon cancer development in humans or animals, attenuation of the colonic cell surface receptor guanylyl cyclase C (GUCY2C) that occurs due to loss of its paracrine hormone ligand guanylin contributes universally to malignant progression. In this study, we explored a link between obesity and GUCY2C silencing in colorectal cancer. Using genetically engineered mice on different diets, we found that diet-induced obesity caused a loss of guanylin expression in the colon with subsequent GUCY2C silencing, epithelial dysfunction, and tumorigenesis. Mechanistic investigations revealed that obesity reversibly silenced guanylin expression through calorie-dependent induction of endoplasmic reticulum stress and the unfolded protein response in intestinal epithelial cells. In transgenic mice, enforcing specific expression of guanylin in intestinal epithelial cells restored GUCY2C signaling, eliminating intestinal tumors associated with a high calorie diet. Our findings show how caloric suppression of the guanylin-GUCY2C signaling axis links obesity to negation of a universal tumor suppressor pathway in colorectal cancer, suggesting an opportunity to prevent colorectal cancer in obese patients through hormone replacement with the FDA-approved oral GUCY2C ligand linaclotide. ©2016 American Association for Cancer Research.

  5. Structure-function relationship of thiazolide-induced apoptosis in colorectal tumor cells.

    Science.gov (United States)

    Brockmann, Anette; Strittmatter, Tobias; May, Sarah; Stemmer, Kerstin; Marx, Andreas; Brunner, Thomas

    2014-07-18

    Thiazolides are a novel class of anti-infectious agents against intestinal intracellular and extracellular protozoan parasites, bacteria, and viruses. While the parent compound nitazoxanide (NTZ; 2-(acetolyloxy)-N-(5-nitro-2-thiazolyl)benzamide) has potent antimicrobial activity, the bromo-thiazolide RM4819 (N-(5-bromothiazol-2-yl)-2-hydroxy-3-methylbenzamide) shows only reduced activity. Interestingly, both molecules are able to induce cell death in colon carcinoma cell lines, indicating that the molecular target in intestinal pathogens and in colon cancer cells is different. The detoxification enzyme glutathione S-transferase of class Pi 1 (GSTP1) is frequently overexpressed in various tumors, including colon carcinomas, and limits the efficacy of antitumor chemotherapeutic drugs due to its detoxifying activities. In colorectal tumor cells RM4819 has been shown to interact with GSTP1, and GSTP1 enzymatic activity is required for thiazolide-induced apoptosis. At present it is unclear which molecular structures of RM4819 are required to interact with GSTP1 and to induce cell death in colon carcinoma cell lines. Here, we demonstrate that novel thiazolide derivatives with variation in their substituents of the benzene ring do not significantly affect apoptosis induction in Caco-2 cells, whereas removal of the bromide atom on the thiazole ring leads to a strong reduction of cell death induction in colon cancer cells. We further show that active thiazolides require caspase activation and GSTP1 expression in order to induce apoptosis. We demonstrate that increased glutathione (GSH) levels sensitize colon cancer cells to thiazolides, indicating that both GSTP1 enzymatic activity as well as GSH levels are critical factors in thiazolide-induced cell death.

  6. Insulin-induced gene 2 expression correlates with colorectal cancer metastasis and disease outcome.

    Science.gov (United States)

    Sun, Shengjie; Zhang, Guoqing; Sun, Qiong; Wu, Zhiyong; Shi, Weiwei; Yang, Bo; Li, Ying

    2016-01-01

    Colorectal cancer (CRC) is one of the most common cancers worldwide accounting for ∼9% of cancer-related deaths, 90% of which are due to metastasis resulting from resistance to chemotherapeutic agents. Hence, it is imperative to develop novel biomarkers of CRC. Insulin-induced gene 2 (INSIG2) has been previously reported to be a negative regulator of cholesterol synthesis and was recently identified as a putative-positive prognostic biomarker for colon and pancreatic cancer prognosis. Even though it has been suggested as a colon cancer biomarker and as an inhibitor of Bax-mediated apoptosis, the role of INSIG2 in CRC is elusive. We initially validated that INSIG2 is a gene with univariate-negative prognostic capacity to discriminate human colon cancer survivorship and that if present along with adenomatous polyposis coli (APC) gene mutations further decrease overall survival. Gain- and loss-of-function studies of INSIG2 showed that the gene product is responsible for inducing migration and invasion and maintenance of the mesenchymal phenotype in vitro and metastasis in vivo. Interestingly, loss of INSIG2 did not affect tumorigenic potential per se, but affected hepatic invasion in a xenograft assay. Our findings reinforce that INSIG2 is a novel colon cancer biomarker, and suggest, for the first time, an exclusive connection between INSIG2 and metastatic dissemination without any effect on tumorigenesis. © 2015 IUBMB Life, 68(1):65-71, 2016.

  7. Radiation Promotes Colorectal Cancer Initiation and Progression by Inducing Senescence-Associated Inflammatory Responses

    Science.gov (United States)

    Kim, Sang Bum; Bozeman, Ronald; Kaisani, Aadil; Kim, Wanil; Zhang, Lu; Richardson, James A.; Wright, Woodring E.; Shay, Jerry W.

    2015-01-01

    Proton radiotherapy is becoming more common since protons induce more precise DNA damage at the tumor site with reduced side effects to adjacent normal tissues. However, the long-term biological effects of proton irradiation in cancer initiation compared to conventional photon irradiation are poorly characterized. In this study, using a human familial adenomatous polyposis syndrome susceptible mouse model, we show that whole body irradiation with protons are more effective in inducing senescence-associated inflammatory responses (SIR) which are involved in colon cancer initiation and progression. After proton irradiation, a subset of SIR genes (Troy, Sox17, Opg, Faim2, Lpo, Tlr2 and Ptges) and a gene known to be involved in invasiveness (Plat), along with the senescence associated gene (P19Arf) are markedly increased. Following these changes loss of Casein kinase Iα (CKIα) and induction of chronic DNA damage and TP53 mutations are increased compared to x-ray irradiation. Proton irradiation also increases the number of colonic polyps, carcinomas and invasive adenocarcinomas. Pretreatment with the non-steroidal anti-inflammatory drug, CDDO-EA, reduces proton irradiation associated SIR and tumorigenesis. Thus, exposure to proton irradiation elicits significant changes in colorectal cancer initiation and progression that can be mitigated using CDDO-EA. PMID:26477319

  8. Alcohol induces cell proliferation via hypermethylation of ADHFE1 in colorectal cancer cells.

    Science.gov (United States)

    Moon, Ji Wook; Lee, Soo Kyung; Lee, Yong Woo; Lee, Jung Ok; Kim, Nami; Lee, Hye Jeong; Seo, Jung Seon; Kim, Jin; Kim, Hyeon Soo; Park, Sun-Hwa

    2014-05-28

    The hypermethylation of Alcohol dehydrogenase iron containing 1 (ADHFE1) was recently reported to be associated with colorectal cancer (CRC) differentiation. However, the effect of alcohol on ADHFE1 hypermethylation in CRC is still unclear. The methylation status and expression levels of ADHFE1 were investigated in primary tumor tissues and adjacent normal tissues of 73 patients with CRC, one normal colon cell line, and 4 CRC cell lines (HT-29, SW480, DLD-1, and LoVo) by quantitative methylation-specific polymerase chain reaction (QMSP) and real-time reverse transcription polymerase chain reaction (real time PCR), respectively. The effect of alcohol on the methylation status of ADHFE1 was analyzed in HT-29, SW480, DLD-1, and CCD18Co cells using QMSP, real-time PCR, immunoblot, and cell proliferation assay. ADHFE1 was hypermethylated in 69 of 73 CRC tissues (95%) compared to adjacent normal tissues (palcohol consumption group (pAlcohol induced hypermethylation of ADHFE1, decreased its expression, and stimulated cell proliferation of HT-29, SW480, and DLD-1cells. These results demonstrate that the promoter hypermethylation of ADHFE1 is frequently present in CRC and alcohol induces methylation-mediated down expression of ADHFE1 and proliferation of CRC cells.

  9. Desacetyluvaricin induces S phase arrest in SW480 colorectal cancer cells through superoxide overproduction.

    Science.gov (United States)

    Xue, Jun-Yi; Zhou, Guang-Xiong; Chen, Tianfeng; Gao, Si; Choi, Mei-Yuk; Wong, Yum-Shing

    2014-03-01

    Annonaceous acetogenins (ACGs) are a group of fatty acid-derivatives with potent anticancer effects. In the present study, we found desacetyluvaricin (Dau) exhibited notable in vitro antiproliferative effect on SW480 human colorectal carcinoma cells with IC50 value of 14 nM. The studies on the underlying mechanisms revealed that Dau inhibited the cancer cell growth through induction of S phase cell cycle arrest from 11.3% (control) to 33.2% (160 nM Dau), which was evidenced by the decreased protein expression of cyclin A Overproduction of superoxide, intracellular DNA damage, and inhibition of MEK/ERK signaling pathway, were also found involved in cells exposed to Dau. Moreover, pre-treatment of the cells with ascorbic acid significantly prevented the Dau-induced overproduction of superoxide, DNA damage and cell cycle arrest. Taken together, our results suggest that Dau induces S phase arrest in cancer cells by firstly superoxide overproduction and subsequently the involvement of various signaling pathways.

  10. Ionic Liquids to Replace Hydrazine

    Science.gov (United States)

    Koelfgen, Syri; Sims, Joe; Forton, Melissa; Allan, Barry; Rogers, Robin; Shamshina, Julia

    2011-01-01

    A method for developing safe, easy-to-handle propellants has been developed based upon ionic liquids (ILs) or their eutectic mixtures. An IL is a binary combination of a typically organic cation and anion, which generally produces an ionic salt with a melting point below 100 deg C. Many ILs have melting points near, or even below, room temperature (room temperature ionic liquids, RTILs). More importantly, a number of ILs have a positive enthalpy of formation. This means the thermal energy released during decomposition reactions makes energetic ILs ideal for use as propellants. In this specific work, to date, a baseline set of energetic ILs has been identified, synthesized, and characterized. Many of the ILs in this set have excellent performance potential in their own right. In all, ten ILs were characterized for their enthalpy of formation, density, melting point, glass transition point (if applicable), and decomposition temperature. Enthalpy of formation was measured using a microcalorimeter designed specifically to test milligram amounts of energetic materials. Of the ten ILs characterized, five offer higher Isp performance than hydrazine, ranging between 10 and 113 seconds higher than the state-of-the-art propellant. To achieve this level of performance, the energetic cations 4- amino-l,2,4-triazolium and 3-amino-1,2,4-triazolium were paired with various anions in the nitrate, dicyanamide, chloride, and 3-nitro-l,2,4-triazole families. Protonation, alkylation, and butylation synthesis routes were used for creation of the different salts.

  11. Inducing effects of hepatocyte growth factor on the expression of vascular endothelial growth factor in human colorectal carcinoma cells through MEK and PI3K signaling pathways

    Institute of Scientific and Technical Information of China (English)

    ZHANG Yu-hua; WEI Wei; XU Hao; WANG Yan-yan; WU Wen-xi

    2007-01-01

    Background Vascular endothelial growth factor plays a key role in human colorectal carcinoma invasion and metastasis. However, the regulation mechanism remains unknown. Recent studies have shown that several cytokines can regulate the expression of vascular endothelial growth factor in tumor cells. In this study, we investigated whether hepatocyte growth factor can regulate the expression of vascular endothelial growth factor in colorectal carcinoma cells.Methods Hepatocyte growth factor and vascular endothelial growth factor in human serum were measured by ELISA.The mRNA level of vascular endothelial growth factor was analyzed by reverse transcription-PCR. Western blot assay was performed to evaluate levels of c-Met and several other proteins involved in the MAPK and PI3K signaling pathways in colorectal carcinoma cells.Results Serum hepatocyte growth factor and vascular endothelial growth factor were significantly increased in colorectal carcinoma subjects. In vitro extraneous hepatocyte growth factor markedly increased protein and mRNA levels of vascular endothelial growth factor in colorectal carcinoma cells. Hepatocyte growth factor induced phosphorylation of c-Met, ERK1/2 and AKT in a dose-dependent manner. Specific inhibitors on MEK and PI3K inhibited the hepatocyte growth factor-induced expression of vascular endothelial growth factor in colorectal carcinoma cells.Conclusion This present study indicates that hepatocyte growth factor upregulates the expression of vascular endothelial growth factor in colorectal carcinoma cells via the MEK/ERK and PI3K/AKT signaling pathways.

  12. Intrarectal vaccination with recombinant vaccinia virus expressing carcinoembronic antigen induces mucosal and systemic immunity and prevents progression of colorectal cancer.

    Science.gov (United States)

    Kim-Schulze, Seunghee; Kim, Hong Sung; Wainstein, Alberto; Kim, Dae Won; Yang, Wein Cui; Moroziewicz, Dorota; Mong, Phyllus Y; Bereta, Michal; Taback, Bret; Wang, Qin; Kaufman, Howard L

    2008-12-01

    The gastrointestinal mucosa contains an intact immune system that protects the host from pathogens and communicates with the systemic immune system. Absorptive epithelial cells in the mucosa give rise to malignant tumors although the interaction between tumor cells and the mucosal immune system is not well defined. The pathophysiology of colorectal cancer has been elucidated through studies of hereditary syndromes, such as familial adenomatous polyposis, a cancer predisposition syndrome caused by germline mutations in the adenomatous polyposis coli tumor suppressor gene. Patients with FAP develop adenomas and inevitably progress to invasive carcinomas by the age of 40. To better delineate the role of mucosal immunity in colorectal cancer, we evaluated the efficacy of intrarectal recombinant vaccinia virus expressing the human carcinoembryonic Ag (CEA) in a murine FAP model in which mice are predisposed to colorectal cancer and also express human CEA in the gut. Mucosal vaccination reduced the incidence of spontaneous adenomas and completely prevented progression to invasive carcinoma. The therapeutic effects were associated with induction of mucosal CEA-specific IgA Ab titers and CD8(+) CTLs. Mucosal vaccination was also associated with an increase in systemic CEA-specific IgG Ab titers, CD4(+) and CD8(+) T cell responses and resulted in growth inhibition of s.c. implanted CEA-expressing tumors suggesting communication between mucosal and systemic immune compartments. Thus, intrarectal vaccination induces mucosal and systemic antitumor immunity and prevents progression of spontaneous colorectal cancer. These results have implications for the prevention of colorectal cancer in high-risk individuals.

  13. Salvianolic acid B, a novel autophagy inducer, exerts antitumor activity as a single agent in colorectal cancer cells.

    Science.gov (United States)

    Jing, Zhao; Fei, Weiqiang; Zhou, Jichun; Zhang, Lumin; Chen, Liuxi; Zhang, Xiaomin; Liang, Xiao; Xie, Jiansheng; Fang, Yong; Sui, Xinbing; Han, Weidong; Pan, Hongming

    2016-09-20

    Salvianolic Acid B (Sal B), an active compound extracted from the Chinese herb Salvia miltiorrhiza, is attracting more and more attention due to its biological activities, including antioxidant, anticoagulant and antitumor effects. However, autophagy induction in cancer cells by Sal B has never been recognized. In this study, we demonstrated that Sal B induced cell death and triggered autophagy in HCT116 and HT29 cells in a dose-dependent manner. Specific inhibition of autophagy by 3-MA or shRNA targeting Atg5 rescued Sal B-induced cell death in vitro and in vivo, suggesting that Sal B-induced autophagy may play a pro-death role and contribute to the cell death of colorectal cancer cell lines. Furthermore, AKT/mTOR signaling pathway was demonstrated to be a critical mediator in regulating Sal B-induced cell death. Overexpression of AKT by the transfection with AKT plasmid or pretreatment with insulin decreased Sal B-induced autophagy and cell death. Inversely, inhibition of AKT by LY294002 treatment markedly enhanced Sal B-induced autophagy and cell death. Taken together, our results demonstrate, for the first time, that Sal B is a novel autophagy inducer and exerts its antitumor activity as a single agent in colorectal cancer cells through the suppression of AKT/mTOR pathway.

  14. Sodium butyrate induces DRP1-mediated mitochondrial fusion and apoptosis in human colorectal cancer cells.

    Science.gov (United States)

    Tailor, Dhanir; Hahm, Eun-Ryeong; Kale, Raosaheb K; Singh, Shivendra V; Singh, Rana P

    2014-05-01

    Sodium butyrate (NaBt) is the byproduct of anaerobic microbial fermentation inside the gastro-intestinal tract that could reach up to 20mM, and has been shown to inhibit the growth of various cancers. Herein, we evaluated its effect on mitochondrial fusion and associated induction of apoptosis in colorectal cancer cells (CRC). NaBt treatment at physiological (1-5mM) concentrations for 12 and 24h decreased the cell viability and induced G2-M phase cell cycle arrest in HCT116 (12h) and SW480 human CRC cells. This cell cycle arrest was associated with mitochondria-mediated apoptosis accompanied by a decrease in survivin and Bcl-2 expression, and generation of reactive oxygen species (ROS). Furthermore, NaBt treatment resulted in a significant decrease in the mitochondrial mass which is an indicator of mitochondrial fusion. Level of dynamin-related protein 1 (DRP1), a key regulator of mitochondrial fission and fusion where its up-regulation correlates with fission, was found to be decreased in CRC cells. Further, at early treatment time, DRP1 down-regulation was noticed in mitochondria which later became drastically reduced in both mitochondria as well as cytosol. DRP1 is activated by cyclin B1-CDK1 complex by its ser616 phosphorylation in which both cyclin B1-CDK1 complex and phospho-DRP1 (ser616) were strongly reduced by NaBt treatment. DRP1 was observed to be regulated by apoptosis as pan-caspase inhibitor showing rescue from NaBt-induced apoptosis also caused the reversal of DRP1 to the normal level as in control proliferating cells. Together, these findings suggest that NaBt can modulate mitochondrial fission and fusion by regulating the level of DRP1 and induce cell cycle arrest and apoptosis in human CRC cells.

  15. STAT3-dependent TXNDC17 expression mediates Taxol resistance through inducing autophagy in human colorectal cancer cells.

    Science.gov (United States)

    Zhang, Zhongde; Wang, Aihua; Li, Hui; Zhi, Hui; Lu, Feng

    2016-06-10

    Taxol (paclitaxel) is one of the taxane class of anticancer drugs as a first-line chemotherapeutic agent against many cancers including colorectal cancer, breast cancer, non-small cell lung cancer, ovarian cancer and so on. It is verified to induce cytotoxicity in a concentration and time-dependent manner. Numerous novel formulations of Taxol have been remanufactured for better therapeutic effect. Though Taxol works as a common anticancer drug for a long time in clinical practice, drug resistance is a major limitation of its long-term administration. In-depth research on drug resistance is still in progress and researchers have made some achievements, however, the mechanism or key molecule related to Taxol resistance in colorectal cancer still remains to be explored. In the present study, we observed that the high expression of TXNDC17 (thioredoxin domain containing 17) was associated with Taxol resistance in colorectal cancer cells. And TXNDC17 mediated Taxol resistance was related with increased basal autophagy level. Taxol exposure induced high levels of phospho-STAT3 (Tyr 705) and TXNDC17; and increase of basal autophagy in colorectal cancer cells. TXNDC17 overexpression cells obtained Taxol resistance and a high level of autophagy, and it is not surprising that stable downregulation of TXNDC17 accordingly reversed these phenomena. Interestingly, STAT3 could similarly work as TXNDC17 in spite of slighter effect compared to TXNDC17. And it has been proved that phospho-STAT3 (Tyr 705) possesses transcriptional regulation activity through forming dimmers. Many research revealed that transcription factor STAT3 affected more than 1000 gene products, and TXNDC17 is predicted to be a target gene of STAT3 at UCSC database. For the first time, we found STAT3 could bind promoter region of TXNDC17 (-623 bp to -58 bp relative to the transcription start site (TSS)) for regulating its expression. These results suggest the possibility that TXNDC17 could play an important role

  16. DDX3 enhances oncogenic KRAS-induced tumor invasion in colorectal cancer via the β-catenin/ZEB1 axis

    Science.gov (United States)

    Wu, De-Wei; Lin, Po-Lin; Cheng, Ya-Wen; Huang, Chi-Chou; Wang, Lee; Lee, Huei

    2016-01-01

    DDX3 plays a dual role in colorectal cancer; however, the role and underlying mechanism of DDX3 in colorectal tumorigenesis remains unclear. Here, we provide evidence that DDX3 enhances oncogenic KRAS transcription via an increase in SP1 binding to its promoter. Accelerating oncogenic KRAS expression by DDX3 promotes the invasion capability via the ERK/PTEN/AKT/β-catenin cascade. Moreover, the β-catenin/ZEB1 axis is responsible for DDX3-induced cell invasiveness and xenograft lung tumor nodule formation. The xenograft lung tumor nodules induced by DDX3-overexpressing T84 stable clone were nearly suppressed by the inhibitor of AKT (perifosine) or β-catenin (XAV939). Among patients, high KRAS, positive nuclear β-catenin expression and high ZEB1 were more commonly occurred in high-DDX3 tumors than in low-DDX3 tumors. High-DDX3, high-KRAS, positive nuclear β-catenin tumors, and high-ZEB1 exhibited worse overall survival (OS) and relapse free survival (RFS) than their counterparts. In conclusion, DDX3 may play an oncogenic role to promote tumor growth and invasion in colon cancer cells via the β-catenin/ZEB1 axis due to increasing KRAS transcription. We therefore suggest that AKT or β-catenin may potentially act as a therapeutic target to improve tumor regression and outcomes in colorectal cancer patients who harbored high-DDX3 tumors. PMID:27007150

  17. Drug-induced skin toxicity and clinical nursing of VitK cream on colorectal cancer patients.

    Science.gov (United States)

    Li, Ai-Min; Miao, Jin-Hong; Liu, Hui; Ma, Yao-Zhen; Sun, Zhen-Chang

    2015-07-01

    To discuss the impact of 0.1% vitamin K1 (VitK1) cream on cetuximab-induced skin toxicity for colorectal cancer patients. 60 colorectal cancer patients with cetuximab therapy after hospitalization, were divided into experimental group (Ward A) and control group (Ward B) according to personnel sequential number, with 30 cases in each group. Routine nursing was implemented on control group. For experimental group, on the routine nursing basis, 0.1% VitK1 cream was smeared on face, neck, chest, back and nail (toenail) edge with three times one day at the application of cetuximab day. After cetuximab applied in 8 weeks, both skin itch and dry skin for patients in experimental group were significantly improved compared those in control group, showing statistically significant difference (W=708.000, P=0.001: W=662. 500, P=0.000). 0.1% VitK1 cream was conducive to improve both skin itch and dry skin symptoms in the cetuximab-induced skin toxicity for colorectal cancer patients.

  18. Effect of nonsteroidal anti-inflammatory drugs on colorectal distension-induced visceral pain.

    Science.gov (United States)

    Baskın, Veysel; Bilge, S Sırrı; Bozkurt, Ayhan; Akyüz, Bahar; Ağrı, Arzu Erdal; Güzel, Hasan; İlkaya, Fatih

    2016-01-01

    To investigate nonsteroidal anti-inflammatory drugs effectiveness in colorectal distension (CRD)-induced visceral pain model. Male Sprague-Dawley (250-300 g) rats were anesthetized with ketamine (50 mg/kg, intraperitoneally [i.p.]) and chlorpromazine (25 mg/kg, i.p.). Two bipolar Teflon-coated Ni/Cr wire electrodes (80-M diameter) were placed in the abdominal external oblique muscle for the recording of electromyography. Jugular vein catheter was placed for the administration of drugs. CRD method was applied to evaluate of visceral pain. All drugs (paracetamol, meloxicam, metamizole, and dexketoprofen) administered intravenously. Paracetamol 200, 400, and 600 mg/kg did not change the visceromotor response (VMR) when compare with the control group. Meloxicam 2 and 4 mg/kg showed no effect but at doses of 6 mg/kg meloxicam significantly ([51.9 ± 6.4%] [P visceral pain model. This condition can be explained due to different chemical structures and different mechanisms which play a role in modulation of pain.

  19. Effects and mechanisms of auricular electroacupuncture on visceral pain induced by colorectal distension in conscious rats.

    Science.gov (United States)

    Li, Han; Hu, Shasha; Zhang, Jianbin; Zhou, Jingzhu; Ran, Hongxing; Tang, Yichun; Chen, Jiande; Wang, Yinping

    2014-12-01

    To investigate the effects and mechanisms of action of auricular electroacupuncture (AEA) on visceral pain induced by colorectal distension (CRD). Twenty-nine female Sprague-Dawley rats were randomly divided into four groups: control; untreated CRD; CRD+AEA; and CRD+sham electroacupuncture (SEA). An electromyogram (EMG) was recorded for 120 min in the conscious state. After a 30 min baseline recording, CRD was performed in untreated CRD, AEA and SEA groups and lasted for 90 min. AEA and SEA were started at 30 min and lasted for 30 min. The EMG was recorded and analysed to evaluate the severity of visceral pain, indicated by the magnitude of the vasomotor response (VMR). mRNA expression of the 5-hydroxytryptamine 1a (5-HT1a) receptor was measured separately in the colon and raphe nuclei using real-time fluorescent quantitative PCR. No differences were seen in the baseline EMG among the four groups (p>0.05). During pre-stimulation, VMR magnitude in the CRD, AEA and SEA groups increased compared with that in the control group (pvisceral pain in rats, and increase mRNA expression of the 5-HT1a receptor peripherally (in the colon) and centrally (in the raphe nuclei), suggesting a serotonergic mechanism of action. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  20. Comprehensive Suppression of All Apoptosis-Induced Proliferation Pathways as a Proposed Approach to Colorectal Cancer Prevention and Therapy

    Science.gov (United States)

    Bordonaro, Michael; Drago, Eric; Atamna, Wafa; Lazarova, Darina L.

    2014-01-01

    Mutations in the WNT/beta-catenin pathway are present in the majority of all sporadic colorectal cancers (CRCs), and histone deacetylase inhibitors induce apoptosis in CRC cells with such mutations. This apoptosis is counteracted by (1) the signaling heterogeneity of CRC cell populations, and (2) the survival pathways induced by mitogens secreted from apoptotic cells. The phenomena of signaling heterogeneity and apoptosis-induced survival constitute the immediate mechanisms of resistance to histone deacetylase inhibitors, and probably other chemotherapeutic agents. We explored the strategy of augmenting CRC cell death by inhibiting all survival pathways induced by the pro-apoptotic agent LBH589, a histone deacetylase inhibitor: AKT, JAK/STAT, and ERK signaling. The apoptosis-enhancing ability of a cocktail of synthetic inhibitors of proliferation was compared to the effects of the natural product propolis. We utilized colorectal adenoma, drug-sensitive and drug-resistant colorectal carcinoma cells to evaluate the apoptotic potential of the combination treatments. The results suggest that an effective approach to CRC combination therapy is to combine apoptosis-inducing drugs (e.g., histone deacetylase inhibitors, such as LBH589) with agents that suppress all compensatory survival pathways induced during apoptosis (such as the cocktail of inhibitors of apoptosis-associated proliferation). The same paradigm can be applied to a CRC prevention approach, as the apoptotic effect of butyrate, a diet-derived histone deacetylase inhibitor, is augmented by other dietary agents that modulate survival pathways (e.g., propolis and coffee extract). Thus, dietary supplements composed by fermentable fiber, propolis, and coffee extract may effectively counteract neoplastic growth in the colon. PMID:25500581

  1. Treatment for hydrazine-containing waste water solution

    Science.gov (United States)

    Yade, N.

    1986-01-01

    The treatment for waste solutions containing hydrazine is presented. The invention attempts oxidation and decomposition of hydrazine in waste water in a simple and effective processing. The method adds activated charcoal to waste solutions containing hydrazine while maintaining a pH value higher than 8, and adding iron salts if necessary. Then, the solution is aerated.

  2. SNPs in the coding region of the metastasis-inducing gene MACC1 and clinical outcome in colorectal cancer

    Directory of Open Access Journals (Sweden)

    Schmid Felicitas

    2012-07-01

    Full Text Available Abstract Background Colorectal cancer is one of the main cancers in the Western world. About 90% of the deaths arise from formation of distant metastasis. The expression of the newly identified gene metastasis associated in colon cancer 1 (MACC1 is a prognostic indicator for colon cancer metastasis. Here, we analyzed for the first time the impact of single nucleotide polymorphisms (SNPs in the coding region of MACC1 for clinical outcome of colorectal cancer patients. Additionally, we screened met proto-oncogene (Met, the transcriptional target gene of MACC1, for mutations. Methods We sequenced the coding exons of MACC1 in 154 colorectal tumors (stages I, II and III and the crucial exons of Met in 60 colorectal tumors (stages I, II and III. We analyzed the association of MACC1 polymorphisms with clinical data, including metachronous metastasis, UICC stages, tumor invasion, lymph node metastasis and patients’ survival (n = 154, stages I, II and III. Furthermore, we performed biological assays in order to evaluate the functional impact of MACC1 SNPs on the motility of colorectal cancer cells. Results We genotyped three MACC1 SNPs in the coding region. Thirteen % of the tumors had the genotype cg (rs4721888, L31V, 48% a ct genotype (rs975263, S515L and 84% a gc or cc genotype (rs3735615, R804T. We found no association of these SNPs with clinicopathological parameters or with patients’ survival, when analyzing the entire patients’ cohort. An increased risk for a shorter metastasis-free survival of patients with a ct genotype (rs975263 was observed in younger colon cancer patients with stage I or II (P = 0.041, n = 18. In cell culture, MACC1 SNPs did not affect MACC1-induced cell motility and proliferation. Conclusion In summary, the identification of coding MACC1 SNPs in primary colorectal tumors does not improve the prediction for metastasis formation or for patients’ survival compared to MACC1 expression analysis alone. The ct genotype (rs

  3. Pien Tze Huang Inhibits Hypoxia-Induced Angiogenesis via HIF-1α/VEGF-A Pathway in Colorectal Cancer

    Directory of Open Access Journals (Sweden)

    Hongwei Chen

    2015-01-01

    Full Text Available Hypoxia-induced angiogenesis plays an important role in the development and metastasis of solid tumors and is highly regulated by HIF-1α/VEGF-A pathway. Therefore, inhibiting tumor angiogenesis via suppression of HIF-1α/VEGF-A signaling represents a promising strategy for anticancer treatment. As a traditional Chinese medicine formula, Pien Tze Huang (PZH has long been used as a folk remedy for cancer in China and Southeast Asia. Previously, we reported that PZH inhibits colorectal cancer (CRC growth both in vivo and in vitro. To elucidate the antitumor mechanisms of PZH, in the present study we used human umbilical vein endothelial cells (HUVEC and colorectal carcinoma HCT-8 cells to evaluate the effects of PZH on hypoxia-induced angiogenesis and investigated the underlying molecular mechanisms. We found that PZH could inhibit hypoxia-induced migration and tube formation of HUVEC cells in a dose-dependent manner, although the low concentrations of PZH had no effect on HUVEC viability. Moreover, PZH inhibited hypoxia-induced activation of HIF-1α signaling and the expression of VEGF-A and/or VEGFR2 in both HCT-8 and HUVEC cells. Collectively, our findings suggest that PZH can inhibit hypoxia-induced tumor angiogenesis via suppression of HIF-1α/VEGF-A pathway.

  4. Chemopreventive effect of myrtenal on bacterial enzyme activity and the development of 1,2-dimethyl hydrazine-induced aberrant crypt foci in Wistar Rats

    Directory of Open Access Journals (Sweden)

    Lokesh Kumar Booupathy

    2016-01-01

    Full Text Available Colon cancer remains as a serious health problem around the world despite advances in diagnosis and treatment. Dietary fibers are considered to reduce the risk of colon cancer as they are converted to short chain fatty acids by the presence of anaerobic bacteria in the intestine, but imbalanced diet and high fat consumption may promote tumor formation at different sites, including the large bowel via increased bacterial enzymes activity. The present study was conducted to characterize the inhibitory action of myrtenal on bacterial enzymes and aberrant crypt foci (ACF. Experimental colon carcinogenesis induced by 1,2-dimethylhydrazine is histologically, morphologically, and anatomically similar to human colonic epithelial neoplasm. Discrete microscopic mucosal lesions such as ACF and malignant tumors function as important biomarkers in the diagnosis of colon cancer. Methylene blue staining was carried out to visualize the impact of 1,2-dimethylhydrazine and myrtenal. Myrtenal-treated animals showed decreased levels of bacterial enzymes such as β-glucuronidase, β-glucosidase, and mucinase. Characteristic changes in the colon were noticed by inhibiting ACF formation in the colon. In conclusion, treatment with myrtenal provided altered pathophysiological condition in colon cancer-bearing animals with evidence of decreased crypt multiplicity and tumor progression.

  5. Slit-Robo signaling induces malignant transformation through Hakai-mediated E-cadherin degradation during colorectal epithelial cell carcinogenesis

    Institute of Scientific and Technical Information of China (English)

    Wei-Jie Zhou; Yan-Qing Ding; Jian-Guo Geng; Zhen H Geng; Shan Chi; Wenli Zhang; Xiao-Feng Niu; Shu-Jue Lan; Li Ma; Xuesong Yang; Li-Jing Wang

    2011-01-01

    The Slit family of guidance cues binds to Roundabout (Robo) receptors and modulates cell migration. We report here that ectopic expression of Slit2 and Robol or recombinant Slit2 treatment of Robol-expressing colorectal epithelial carcinoma cells recruited an ubiquitin ligase Hakai for E-cadherin (E-cad) ubiquitination and lysosomal degradation, epithelial-mesenchymal transition (EMT), and tumor growth and liver metastasis, which were rescued by knockdown of Hakai. In contrast, knockdown of endogenous Robol or specific blockade of Slit2 binding to Robol prevented E-cad degradation and reversed EMT, resulting in diminished tumor growth and liver metastasis.Ectopic expression of Robol also triggered a malignant transformation in Siit2-positive human embryonic kidney 293 cells. Importantly, the expression of Slit2 and Robol was significantly associated with an increased metastatic risk and poorer overall survival in colorectal carcinoma patients. We conclude that engagement of Robol by Slit2 induces malignant transformation through Hakai-mediated E-cad ubiquitination and lysosomal degradation during colorectal epithelial cell carcinogenesis.

  6. Osteopontin Overexpression Induced Tumor Progression and Chemoresistance to Oxaliplatin through Induction of Stem-Like Properties in Human Colorectal Cancer

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    Lui Ng

    2015-01-01

    Full Text Available Colorectal cancer (CRC is one of the most common and fatal malignancies worldwide. The poor prognosis of colorectal cancer patients is due to development of chemoresistance and cancer metastasis. Recently osteopontin (OPN has been associated with stem-like properties in colorectal cancer. This study further examined the clinicopathological significance of OPN in CRC and its effect on chemoresistance and transcription of stem cell markers. We examined the transcription level of OPN in 84 CRC patients and correlated the expression with their clinicopathological parameters. The associations of OPN overexpression with transcription of stem cell markers and response to chemotherapy in DLD1-OPN overexpressing clones and CRC patients were also investigated. Our results showed that OPN was significantly overexpressed in CRC, and its overexpression correlated with tumor stage and poor prognosis. Overexpression of CRC induced OCT4 and SOX2 expression in vitro and correlated with SOX2 overexpression in CRC patients. In addition, DLD1-OPN overexpressing cells showed enhanced ability to survive upon oxaliplatin treatment, and OPN expression was higher in CRC patients who were resistant to oxaliplatin-involved chemotherapy treatment. Thus, CRC cells overexpressing OPN demonstrated stem-like properties and OPN inhibition is a potential therapeutic approach to combat CRC progression and chemoresistance.

  7. The Hedgehog Inhibitor Cyclopamine Reduces β-Catenin-Tcf Transcriptional Activity, Induces E-Cadherin Expression, and Reduces Invasion in Colorectal Cancer Cells

    Energy Technology Data Exchange (ETDEWEB)

    Qualtrough, David, E-mail: david.qualtrough@uwe.ac.uk [Department of Biological, Biomedical & Analytical Sciences, University of the West of England, Faculty of Health and Applied Sciences, University of the West of England, Frenchay, Bristol BS16 1QY (United Kingdom); Rees, Phil; Speight, Beverley; Williams, Ann C.; Paraskeva, Christos [School of Cellular & Molecular Medicine, University of Bristol, Medical Sciences Building, University Walk, Bristol BS8 1TD (United Kingdom)

    2015-09-17

    Colorectal cancer is a major global health problem resulting in over 600,000 deaths world-wide every year with the majority of these due to metastatic disease. Wnt signalling, and more specifically β-catenin-related transcription, has been shown to drive both tumorigenesis and the metastatic process in colorectal neoplasia, yet its complex interactions with other key signalling pathways, such as hedgehog, remain to be elucidated. We have previously shown that the Hedgehog (HH) signalling pathway is active in cells from colorectal tumours, and that inhibition of the pathway with cyclopamine induces apoptosis. We now show that cyclopamine treatment reduces β-catenin related transcription in colorectal cancer cell lines, and that this effect can be reversed by addition of Sonic Hedgehog protein. We also show that cyclopamine concomitantly induces expression of the tumour suppressor and prognostic indicator E-cadherin. Consistent with a role for HH in regulating the invasive potential we show that cyclopamine reduces the expression of transcription factors (Slug, Snail and Twist) associated with the epithelial-mesenchymal transition and reduces the invasiveness of colorectal cancer cells in vitro. Taken together, these data show that pharmacological inhibition of the hedgehog pathway has therapeutic potential in the treatment of colorectal cancer.

  8. The Hedgehog Inhibitor Cyclopamine Reduces β-Catenin-Tcf Transcriptional Activity, Induces E-Cadherin Expression, and Reduces Invasion in Colorectal Cancer Cells

    Directory of Open Access Journals (Sweden)

    David Qualtrough

    2015-09-01

    Full Text Available Colorectal cancer is a major global health problem resulting in over 600,000 deaths world-wide every year with the majority of these due to metastatic disease. Wnt signalling, and more specifically β-catenin-related transcription, has been shown to drive both tumorigenesis and the metastatic process in colorectal neoplasia, yet its complex interactions with other key signalling pathways, such as hedgehog, remain to be elucidated. We have previously shown that the Hedgehog (HH signalling pathway is active in cells from colorectal tumours, and that inhibition of the pathway with cyclopamine induces apoptosis. We now show that cyclopamine treatment reduces β-catenin related transcription in colorectal cancer cell lines, and that this effect can be reversed by addition of Sonic Hedgehog protein. We also show that cyclopamine concomitantly induces expression of the tumour suppressor and prognostic indicator E-cadherin. Consistent with a role for HH in regulating the invasive potential we show that cyclopamine reduces the expression of transcription factors (Slug, Snail and Twist associated with the epithelial-mesenchymal transition and reduces the invasiveness of colorectal cancer cells in vitro. Taken together, Cancers 2015, 7 1886 these data show that pharmacological inhibition of the hedgehog pathway has therapeutic potential in the treatment of colorectal cancer.

  9. Hydrazine in the Ugi Tetrazole Reaction

    NARCIS (Netherlands)

    Patil, Pravin; Zhang, Ji; Kurpiewska, Katarzyna; Kalinowska-Tłuścik, Justyna; Dömling, Alexander

    2016-01-01

    We describe the hitherto unknown use of N-Boc-protected hydrazine in the Ugi tetrazole reaction to access a library of highly substituted 5-(hydrazinomethyl)-1-methyl-1H-tetrazoles. The reaction is very versatile and good to high yielding. A one-pot, two-step procedure is given.

  10. Oxaliplatin-Induced Peripheral Neuropathy and Identification of Unique Severity Groups in Colorectal Cancer.

    Science.gov (United States)

    Griffith, Kathleen A; Zhu, Shijun; Johantgen, Meg; Kessler, Michael D; Renn, Cynthia; Beutler, Andreas S; Kanwar, Rahul; Ambulos, Nicholas; Cavaletti, Guido; Bruna, Jordi; Briani, Chiara; Argyriou, Andreas A; Kalofonos, Haralabos P; Yerges-Armstrong, Laura M; Dorsey, Susan G

    2017-07-22

    Oxaliplatin-induced peripheral neuropathy (OIPN) is a dose limiting toxicity of oxaliplatin and affects most colorectal cancer (CRC) patients. OIPN is commonly evaluated by patient symptom report, using scales to reflect impairment. They do not discriminate between unique grouping of symptoms and signs, which impedes prompt identification of OIPN. Our study objective was to identify clusters of symptoms and signs that differentiated underlying clinical severity and segregated patients within our population into OIPN subgroups. Chemotherapy naïve CRC patients (N=148) receiving oxaliplatin were administered the Total Neuropathy Score clinical (TNSc(©)), which includes symptom report (sensory, motor, autonomic) and sensory examination (pin sense, vibration, reflexes). The TNSc(©) was administered prior to chemotherapy initiation (T0), and following cumulative doses of oxaliplatin 510-520 mg/m(2) (T1) and 1020-1040 mg/ m(2) of oxaliplain (T2). Using mean T2 TNSc(©) scores, latent class analysis (LCA) grouped patients into OIPN severity cohorts. LCA categorized patients into 4 distinct OIPN groups: low symptoms and low signs (N=54); low symptoms and intermediate signs (n=44); low symptoms and high signs (n=21); and high symptoms and high signs (n=29). No differences were noted among OIPN groups on age, sex, chemotherapy regimen, or cumulative oxaliplatin dose. We identified OIPN patient groups with distinct symptoms/signs, demonstrating variability of OIPN presentation regardless of cumulative oxaliplatin dose. Over half of the sample had positive findings on OIPN examination despite little or no symptoms. Sensory examination of all patients receiving oxaliplatin is indicated for timely identification of OIPN, which will allow earlier symptom management. Copyright © 2017. Published by Elsevier Inc.

  11. β-Lapachone Inhibits Lung Metastasis of Colorectal Cancer by Inducing Apoptosis of CT26 Cells.

    Science.gov (United States)

    Kee, Ji-Ye; Han, Yo-Han; Park, Jinbong; Kim, Dae-Seung; Mun, Jeong-Geon; Ahn, Kwang Seok; Kim, Hyun-Jung; Um, Jae-Young; Hong, Seung-Heon

    2016-12-05

    β-Lapachone is a quinone-containing compound found in red lapacho (Tabebuia impetiginosa, syn. T avellanedae) trees. Lapacho has been used in traditional medicine by several South and Central American indigenous people to treat various types of cancer. The purpose of this study was to investigate the antimetastatic properties of β-lapachone and the underlying mechanisms using colon cancer cells. This research used metastatic murine colon cancer cell lines, colon 26 (CT26) and colon 38 (MC38). A WST assay, annexin V assay, cell cycle analysis, wound healing assay, invasion assay, western blot analysis, and real-time reverse transcription-polymerase chain reaction were performed to examine the effects of β-lapachone on metastatic phenotypes and molecular mechanisms. The effect of β-lapachone on lung metastasis was assessed in a mouse experimental metastasis model. We found that the inhibition of proliferation of the colon cancer cell lines by β-lapachone was due to the induction of apoptosis and cell cycle arrest. β-Lapachone induced the apoptosis of CT26 cells through caspase-3, -8, and -9 activation; poly(ADP-ribose) polymerase cleavage; and downregulation of the Bcl-2 family in a dose- and time-dependent manner. In addition, a low concentration of β-lapachone decreased the cell migration and invasion by decreasing the expression of matrix metalloproteinases-2 and -9, and increased the expression of tissue inhibitors of metalloproteinases-1 and -2. Moreover, β-lapachone treatment regulated the expression of epithelial-mesenchymal transition markers such as E- and N-cadherin, vimentin, β-catenin, and Snail in CT26 cells. In the mouse experimental metastasis model, β-lapachone significantly inhibited the lung metastasis of CT26 cells. Our results demonstrated the inhibitory effect of β-lapachone on colorectal lung metastasis. This compound may be useful for developing therapeutic agents to treat metastatic cancer. © The Author(s) 2016.

  12. What Is Colorectal Cancer?

    Science.gov (United States)

    ... Research? Colorectal Cancer About Colorectal Cancer What Is Colorectal Cancer? Colorectal cancer is a cancer that starts in ... and spread, see What Is Cancer? How does colorectal cancer start? Most colorectal cancers begin as a growth ...

  13. Crystal structure of hydrazine iron(III) phosphate, the first transition metal phosphate containing hydrazine.

    Science.gov (United States)

    David, Renald

    2015-12-01

    The title compound, poly[(μ2-hydrazine)(μ4-phosphato)iron(III)], [Fe(PO4)(N2H4)] n , was prepared under hydro-thermal conditions. Its asymmetric unit contains one Fe(III) atom located on an inversion centre, one P atom located on a twofold rotation axis, and two O, one N and two H atoms located on general positions. The Fe(III) atom is bound to four O atoms of symmetry-related PO4 tetra-hedra and to two N atoms of two symmetry-related hydrazine ligands, resulting in a slightly distorted FeO4N2 octa-hedron. The crystal structure consists of a three-dimensional hydrazine/iron phoshate framework whereby each PO4 tetra-hedron bridges four Fe(III) atoms and each hydrazine ligand bridges two Fe(III) atoms. The H atoms of the hydrazine ligands are also involved in moderate N-H⋯O hydrogen bonding with phosphate O atoms. The crystal structure is isotypic with the sulfates [Co(SO4)(N2H4)] and [Mn(SO4)(N2H4)].

  14. Crystal structure of hydrazine iron(III phosphate, the first transition metal phosphate containing hydrazine

    Directory of Open Access Journals (Sweden)

    Renald David

    2015-12-01

    Full Text Available The title compound, poly[(μ2-hydrazine(μ4-phosphatoiron(III], [Fe(PO4(N2H4]n, was prepared under hydrothermal conditions. Its asymmetric unit contains one FeIII atom located on an inversion centre, one P atom located on a twofold rotation axis, and two O, one N and two H atoms located on general positions. The FeIII atom is bound to four O atoms of symmetry-related PO4 tetrahedra and to two N atoms of two symmetry-related hydrazine ligands, resulting in a slightly distorted FeO4N2 octahedron. The crystal structure consists of a three-dimensional hydrazine/iron phoshate framework whereby each PO4 tetrahedron bridges four FeIII atoms and each hydrazine ligand bridges two FeIII atoms. The H atoms of the hydrazine ligands are also involved in moderate N—H...O hydrogen bonding with phosphate O atoms. The crystal structure is isotypic with the sulfates [Co(SO4(N2H4] and [Mn(SO4(N2H4].

  15. Silence of long noncoding RNA PANDAR switches low-dose curcumin-induced senescence to apoptosis in colorectal cancer cells

    Directory of Open Access Journals (Sweden)

    Chen T

    2017-01-01

    Full Text Available Tao Chen,1,* Peng Yang,1,* Hui Wang,1 Zhen-Yu He2 1Department of General Surgery, The Second Clinical Medical College of Nanjing Medical University, 2Department of General Surgery, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of China *These authors contributed equally to this work Abstract: Long noncoding RNAs (lncRNAs are emerging as having multiple roles in cancer progression. However, roles of lncRNAs in chemotherapy for colorectal cancer (CRC remain unclear. This study investigated the biological functions of lncRNA PANDAR in CRC cells treated with curcumin chemotherapy. Herein, we identified that PANDAR expression was not notably differential in CRC tissues compared with the corresponding normal tissues. Consistently, in vitro experiments revealed that knockdown of PANDAR could not change the proliferation, apoptosis, or senescence of CRC cells. Further analyses showed that low-dose curcumin could induce senescence in CRC cells without affecting cell apoptosis. Moreover, expression of PANDAR was increased in curcumin-treated CRC cells. Furthermore, silencing PANDAR in curcumin-treated cells increased apoptosis and greatly attenuated senescence possibly by stimulating the expression of PUMA. Together, these findings indicate that knockdown of lncRNA PANDAR switches curcumin-induced senescence to apoptosis, which may be potentially valuable in CRC therapy. Keywords: colorectal cancer, long noncoding RNA, PANDAR, curcumin, chemotherapy

  16. Autophagy promotes resistance to photodynamic therapy-induced apoptosis selectively in colorectal cancer stem-like cells.

    Science.gov (United States)

    Wei, Ming-Feng; Chen, Min-Wei; Chen, Ke-Cheng; Lou, Pei-Jen; Lin, Susan Yun-Fan; Hung, Shih-Chieh; Hsiao, Michael; Yao, Cheng-Jung; Shieh, Ming-Jium

    2014-07-01

    Recent studies have indicated that cancer stem-like cells (CSCs) exhibit a high resistance to current therapeutic strategies, including photodynamic therapy (PDT), leading to the recurrence and progression of colorectal cancer (CRC). In cancer, autophagy acts as both a tumor suppressor and a tumor promoter. However, the role of autophagy in the resistance of CSCs to PDT has not been reported. In this study, CSCs were isolated from colorectal cancer cells using PROM1/CD133 (prominin 1) expression, which is a surface marker commonly found on stem cells of various tissues. We demonstrated that PpIX-mediated PDT induced the formation of autophagosomes in PROM1/CD133(+) cells, accompanied by the upregulation of autophagy-related proteins ATG3, ATG5, ATG7, and ATG12. The inhibition of PDT-induced autophagy by pharmacological inhibitors and silencing of the ATG5 gene substantially triggered apoptosis of PROM1/CD133(+) cells and decreased the ability of colonosphere formation in vitro and tumorigenicity in vivo. In conclusion, our results revealed a protective role played by autophagy against PDT in CSCs and indicated that targeting autophagy could be used to elevate the PDT sensitivity of CSCs. These findings would aid in the development of novel therapeutic approaches for CSC treatment.

  17. Poly-γ-Glutamic Acid Induces Apoptosis via Reduction of COX-2 Expression in TPA-Induced HT-29 Human Colorectal Cancer Cells

    Directory of Open Access Journals (Sweden)

    Eun Ju Shin

    2015-04-01

    Full Text Available Poly-γ-glutamic acid (PGA is one of the bioactive compounds found in cheonggukjang, a fast-fermented soybean paste widely utilized in Korean cooking. PGA is reported to have a number of beneficial health effects, and interestingly, it has been identified as a possible anti-cancer compound through its ability to promote apoptosis in cancer cells, although the precise molecular mechanisms remain unclear. Our findings demonstrate that PGA inhibits the pro-proliferative functions of the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA, a known chemical carcinogen in HT-29 human colorectal cancer cells. This inhibition was accompanied by hallmark apoptotic phenotypes, including DNA fragmentation and the cleavage of poly (ADP-ribose polymerase (PARP and caspase 3. In addition, PGA treatment reduced the expression of genes known to be overexpressed in colorectal cancer cells, including cyclooxygenase 2 (COX-2 and inducible nitric oxide synthase (iNOS. Lastly, PGA promoted activation of 5' adenosine monophosphate-activated protein (AMPK in HT-29 cells. Taken together, our results suggest that PGA treatment enhances apoptosis in colorectal cancer cells, in part by modulating the activity of the COX-2 and AMPK signaling pathways. These anti-cancer functions of PGA make it a promising compound for future study.

  18. Chronic Inhalation Toxicity of Hydrazine: Oncogenic Effects

    Science.gov (United States)

    1981-06-01

    showed signs of anorexia and general fatigue. Changing diets and forced feedings resulted in the survival of the remaining two dogs. A 6-month chronic...Esophagus Bladder Stomach Seminal vesicles Duodenum Prostate Jejunum Testes Ileum Ovaries Cecum Uterus Colon Nasal cavity Rectum Brain Mesenteric lymph... malnutrition during chronic exposure. Based upon these studies, the current OSHA Threshold Limit Value of 1.0 ppm for hydrazine is unsatisfactory while the

  19. 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 ...

  20. Prostaglandin E2-induced colonic secretion in patients with and without colorectal neoplasia

    DEFF Research Database (Denmark)

    Kaltoft, Nicolai; Tilotta, Maria C; Witte, Anne-Barbara;

    2010-01-01

    BACKGROUND: The pathogenesis for colorectal cancer remains unresolved. A growing body of evidence suggests a direct correlation between cyclooxygenase enzyme expression, prostaglandin E2 metabolism and neoplastic development. Thus further understanding of the regulation of epithelial functions...... colorectal neoplasia. Patients without endoscopic findings of neoplasia served as controls. Biopsy specimens were obtained from normally appearing mucosa in the sigmoid part of colon. Biopsies were mounted in miniaturized modified Ussing air-suction chambers. Indomethacin (10 microM), various stimulators...... and inhibitors of prostanoid receptors and ion transport were subsequently added to the chamber solutions. Electrogenic ion transport parameters (short circuit current and slope conductance) were recorded. Tissue pathology and tissue damage before and after experiments was assessed by histology. RESULTS...

  1. Epigenetic changes in colorectal cancer

    Institute of Scientific and Technical Information of China (English)

    Yan Jia; Mingzhou Guo

    2013-01-01

    Epigenetic changes frequently occur in human colorectal cancer.Genomic global hypomethylation,gene promoter region hypermethylation,histone modifications,and alteration of miRNA patterns are major epigenetic changes in colorectal cancer.Loss of imprinting (LOI) is associated with colorectal neoplasia.Folate deficiency may cause colorectal carcinogenesis by inducing gene-specific hypermethylation and genomic global hypomethylation.HDAC inhibitors and demethylating agents have been approved by the FDA for myelodysplastic syndrome and leukemia treatment.Non-coding RNA is regarded as another kind of epigenetic marker in colorectal cancer.This review is mainly focused on DNA methylation,histone modification,and microRNA changes in colorectal cancer.

  2. Fatal posterior revesible leukoencephalopathy syndrome associated coma induced by bevacizumab in metastatic colorectal cancer and review of literature.

    Science.gov (United States)

    Eryılmaz, Melek Karakurt; Mutlu, Hasan; Salim, Derya Kıvrak; Musri, Fatma Yalçın; Coşkun, Hasan Şenol

    2016-12-01

    Posterior reversible leukoencephalopathy syndrome (PRES) is a syndrome characterized by headache, hypertension, confusion, visual disturbance, and seizures accompanied by subcortical vasogenic edema, predominantly involving the parietal and occipital lobes. The syndrome is usually described in malignant hypertension, eclampsia, renal failure, immunosuppressive, and cytotoxic chemotherapies. Bevacizumab, a monoclonal antibody that binds to the vascular endothelial growth factor (VEGF) has been linked to PRES. We carried out review of reports documenting the occurrence of PRES in patients receiving bevacizumab. This literature review was conducted by utilizing PubMed Database. If early diagnosed, PRES is reversible. We present a case of fatal PRES-associated coma induced by bevacizumab in metastatic colorectal cancer. © The Author(s) 2015.

  3. Beclin 1 and UVRAG confer protection from radiation-induced DNA damage and maintain centrosome stability in colorectal cancer cells.

    Directory of Open Access Journals (Sweden)

    Jae Myung Park

    Full Text Available Beclin 1 interacts with UV-irradiation-resistance-associated gene (UVRAG to form core complexes that induce autophagy. While cells with defective autophagy are prone to genomic instability that contributes to tumorigenesis, it is unknown whether Beclin1 or UVRAG can regulate the DNA damage/repair response to cancer treatment in established tumor cells. We found that siRNA knockdown of Beclin 1 or UVRAG can increase radiation-induced DNA double strand breaks (DSBs, shown by pATM and γH2Ax, and promote colorectal cancer cell death. Furthermore, knockdown of Beclin 1, UVRAG or ATG5 increased the percentage of irradiated cells with nuclear foci expressing 53BP1, a marker of nonhomologous end joining but not RAD51 (homologous recombination, compared to control siRNA. Beclin 1 siRNA was shown to attenuate UVRAG expression. Cells with a UVRAG deletion mutant defective in Beclin 1 binding showed increased radiation-induced DSBs and cell death compared to cells with ectopic wild-type UVRAG. Knockdown of Beclin 1 or UVRAG, but not ATG5, resulted in a significant increase in centrosome number (γ-tubulin staining in irradiated cells compared to control siRNA. Taken together, these data indicate that Beclin 1 and UVRAG confer protection against radiation-induced DNA DSBs and may maintain centrosome stability in established tumor cells.

  4. Prostaglandin E2-induced colonic secretion in patients with and without colorectal neoplasia

    Directory of Open Access Journals (Sweden)

    Poulsen Steen S

    2010-01-01

    Full Text Available Abstract Background The pathogenesis for colorectal cancer remains unresolved. A growing body of evidence suggests a direct correlation between cyclooxygenase enzyme expression, prostaglandin E2 metabolism and neoplastic development. Thus further understanding of the regulation of epithelial functions by prostaglandin E2 is needed. We hypothesized that patients with colonic neoplasia have altered colonic epithelial ion transport and express functionally different prostanoid receptor levels in this respect. Methods Patients referred for colonoscopy were included and grouped into patients with and without colorectal neoplasia. Patients without endoscopic findings of neoplasia served as controls. Biopsy specimens were obtained from normally appearing mucosa in the sigmoid part of colon. Biopsies were mounted in miniaturized modified Ussing air-suction chambers. Indomethacin (10 μM, various stimulators and inhibitors of prostanoid receptors and ion transport were subsequently added to the chamber solutions. Electrogenic ion transport parameters (short circuit current and slope conductance were recorded. Tissue pathology and tissue damage before and after experiments was assessed by histology. Results Baseline short circuit current and slope conductance did not differ between the two groups. Patients with neoplasia were significantly more sensitive to indomethacin with a decrease in short circuit current of 15.1 ± 2.6 μA·cm-2 compared to controls, who showed a decrease of 10.5 ± 2.1 μA·cm-2 (p = 0.027. Stimulation or inhibition with theophylline, ouabain, bumetanide, forskolin or the EP receptor agonists prostaglandin E2, butaprost, sulprostone and prostaglandin E1 (OH did not differ significantly between the two groups. Histology was with normal findings in both groups. Conclusions Epithelial electrogenic transport is more sensitive to indomethacin in normal colonic mucosa from patients with previous or present colorectal neoplasia compared

  5. Down-regulation of TCF21 by hypermethylation induces cell proliferation, migration and invasion in colorectal cancer

    Energy Technology Data Exchange (ETDEWEB)

    Dai, Youyi [Department of Oncology, Xiangya Hospital Central South University (China); Duan, Huaxin [Department of Oncology, Hunan Provincial People' s Hospital (China); The First Affiliated Hospital of Hunan Normal University (China); Duan, Chaojun [Cental Lab of Xiangya Hospital Central South University (China); Zhou, Rongrong; He, Yuxiang; Tu, Qingsong [Department of Oncology, Xiangya Hospital Central South University (China); Shen, Liangfang, E-mail: 3153559525@qq.com [Department of Oncology, Xiangya Hospital Central South University (China)

    2016-01-15

    Epigenetic alteration induced loss function of the transcription factor 21 (TCF21) has been associated with different types of human cancers. However, the epigenetic regulation and molecular functions of TCF21 in colorectal cancer (CRC) remain unknown. In this study, TCF21 expression levels and methylation status of its promoter region in CRC cell lines (n = 5) and CRC tissues (n = 151) as well as normal colorectal mucosa (n = 30) were assessed by RTq-PCR and methylation analysis (methylation specific PCR, MSP and bisulfite sequencing PCR, BSP), respectively. The cellular functions of TCF21 on CRC cell proliferation, apoptosis, invasion and migration were investigated in vitro. Our data revealed that TCF21 was frequently silenced by promoter hypermethylation in both tested CRC cell lines and primary CRC, and correlation analysis between methylation status and clinicopathologic parameters found that TCF21 methylation was significantly correlated with lymph node invasion (P = 0.013), while no significant correlation was found in other parameters. In addition, demethylation treatment resulted in re-expression of TCF21 in CRC cell lines, and cellular function experiments revealed that restoration of TCF21 inhibited CRC cell proliferation, promoted apoptosis and suppressed cell invasion and migration, suggesting that TCF21 may function as a tumor suppressor gene, which is downregulated through promoter hypermethylation in CRC development. - Highlights: • TCF21 was frequently silenced by promoter DNA methylation in CRC cells. • TCF21 was frequently methylated in primary CRC and significantly correlated with metastasis. • Restoration of TCF21 promotes cell apoptosis of CRC cells. • Restoration of TCF21 inhibits cell invasion and migration of CRC cells.

  6. Crataegus azarolus Leaves Induce Antiproliferative Activity, Cell Cycle Arrest, and Apoptosis in Human HT-29 and HCT-116 Colorectal Cancer Cells.

    Science.gov (United States)

    Mustapha, Nadia; Pinon, Aline; Limami, Youness; Simon, Alain; Ghedira, Kamel; Hennebelle, Thierry; Chekir-Ghedira, Leila

    2016-05-01

    Limited success has been achieved in extending the survival of patients with metastatic colorectal cancer (CRC). There is a strong need for novel agents in the treatment and prevention of CRC. Therefore, in the present study we evaluated the antiproliferative and pro-apoptotic potential of Crataegus azarolus ethyl acetate extract in HCT-116 and HT-29 human colorectal cancer cell lines. Moreover, we attempted to investigate the signaling pathways that should be involved in its cytotoxic effect. The Crataegus azarolus ethyl acetate extract-induced growth inhibitory effect was associated with DNA fragmentation, sub-G1 peak, loss of mitochondrial potential, and poly (ADP-ribose) polymerase (PARP) cleavage. In addition, ethyl acetate extract of Crataegus azarolus induced the cleavage of caspase-8. It has no effect on steady-state levels of total Bcl-2 protein. Whereas Bax levels decreased significantly in a dose-dependent manner in both tested cell lines. Taken together, these findings confirm the involvement of the extrinsic pathway of apoptosis. The apoptotic cell death induced by ethyl acetate extract of Crataegus azarolus was accompanied by an enhancement of the p21 expression but not through p53 activation in human colorectal cancer cells. The above-mentioned data provide insight into the molecular mechanisms of Crataegus azarolus ethyl acetate extract-induced apoptosis in CRC. Therefore, this compound should be a potential anticancer agent for the treatment of CRC. © 2015 Wiley Periodicals, Inc.

  7. Salidroside induces apoptosis and autophagy in human colorectal cancer cells through inhibition of PI3K/Akt/mTOR pathway.

    Science.gov (United States)

    Fan, Xiang-Jun; Wang, Yao; Wang, Lei; Zhu, Mingyan

    2016-12-01

    The role of salidroside in colon cancer remains unknown. Here we show that salidroside, a phenylpropanoid glycoside extracted from Rhodiola rosea, exhibited potent anti-proliferative properties in human colorectal cancer cells via inducing apoptosis and autophagy. We ascertained that salidroside exerts an inhibitory effect on the proliferation of human colorectal cancer cells in a dose-dependent manner. In addition, salidroside induced cell apoptosis, accompanied by an increase of chromatin condensation and nuclear fragmentation, and a decrease of Bcl-2/Bax protein expression ratio. We also found that salidroside induced autophagy, evidenced by increased LC3+ autophagic vacuoles, positive acridine orange-stained cells, enhanced conversion of LC3-I to LC3-II, and elevation of Beclin-1. Treatment with autophagy-specific inhibitors [3-methyladenine (3-MA) and bafilomycin A1 (BA)] enhanced salidroside-induced apoptosis, indicating that salidroside-mediated autophagy may protect HT29 cells from undergoing apoptotic cell death. Additionally, salidroside decreased the phosphorylation of PI3K, Akt and mTOR. Treatment with PI3K inhibitor LY294002 augmented the effects of salidroside on the expression of Akt and mTOR. These findings indicate that salidroside could suppress the PI3K/Akt/mTOR signaling pathways. This study may provide a rationale for future clinical application using salidroside as a chemotherapeutic agent for human colorectal cancer.

  8. Developing A New Sampling and Analysis Method for Hydrazine and Monomethyl Hydrazine

    Science.gov (United States)

    Allen, John R.

    2002-01-01

    Solid phase microextraction (SPME) will be used to develop a method for detecting monomethyl hydrazine (MMH) and hydrazine (Hz). A derivatizing agent, pentafluorobenzoyl chloride (PFBCl), is known to react readily with MMH and Hz. The SPME fiber can either be coated with PFBCl and introduced into a gaseous stream containing MMH, or PFBCl and MMH can react first in a syringe barrel and after a short equilibration period a SPME is used to sample the resulting solution. These methods were optimized and compared. Because Hz and MMH can degrade the SPME, letting the reaction occur first gave better results. Only MMH could be detected using either of these methods. Future research will concentrate on constructing calibration curves and determining the detection limit.

  9. Developing A New Sampling and Analysis Method for Hydrazine and Monomethyl Hydrazine

    Science.gov (United States)

    Allen, John R.

    2002-01-01

    Solid phase microextraction (SPME) will be used to develop a method for detecting monomethyl hydrazine (MMH) and hydrazine (Hz). A derivatizing agent, pentafluorobenzoyl chloride (PFBCl), is known to react readily with MMH and Hz. The SPME fiber can either be coated with PFBCl and introduced into a gaseous stream containing MMH, or PFBCl and MMH can react first in a syringe barrel and after a short equilibration period a SPME is used to sample the resulting solution. These methods were optimized and compared. Because Hz and MMH can degrade the SPME, letting the reaction occur first gave better results. Only MMH could be detected using either of these methods. Future research will concentrate on constructing calibration curves and determining the detection limit.

  10. Restoration of APC gene function in colorectal cancer cells by aminoglycoside- and macrolide-induced read-through of premature termination codons.

    Science.gov (United States)

    Zilberberg, Alona; Lahav, Lital; Rosin-Arbesfeld, Rina

    2010-04-01

    Adenomatous polyposis coli (APC) is a multifunctional tumour suppressor protein that negatively regulates the Wnt signalling pathway. The APC gene is ubiquitously expressed in tissues and organs, including the large intestine and central nervous system. The majority of patients with sporadic and hereditary colorectal cancer have mutations in the gene encoding APC. Approximately 30% of these mutations are single nucleotide changes that result in premature stop codons (nonsense mutations). A potential therapeutic approach for treatment of this subset of patients is the use of aminoglycosides and macrolides that induce nonsense mutation read-through and restore levels of full-length protein. We have used reporter plasmids and colorectal cancer cell lines to demonstrate that several aminoglycosides and tylosin, a member of the macrolide family, induced read-through of nonsense mutations in the APC gene. In xenograft experiments and in the Apc(Min/+) mouse model, these compounds ameliorated the tumorigenic clinical symptoms caused by nonsense mutations in the APC gene.

  11. IQ (2-amino-3-methylimidazo[4,5-f]quinoline)- induced aberrant crypt foci and colorectal tumour development in rats fed two different carbohydrate diets

    DEFF Research Database (Denmark)

    Mølck, A.M.; Meyer, Otto A.; Kristiansen, E.

    2001-01-01

    In most aberrant crypt foci (ACF) and colorectal tumour studies, chemical carcinogens not normally found in food have been used as initiators. In the present study the food-related compound, IQ (2-amino-3-methylimidazo[4,5-f]quinoline), has been used. A diet high in refined carbohydrates has been...... on the development of IQ-induced ACF over time and (2) possible correlation between early and late ACF and/or colorectal tumour development. The study showed that a feeding regimen with continuous doses of 0.03% IQ in the diet for 14 weeks, followed by 32 weeks without IQ was able to induce tumours in the rat colon...

  12. Protective effects of fullerenol against chronic doxorubicin-induced cardiotoxicity and hepatotoxicity in rats with colorectal cancer

    Directory of Open Access Journals (Sweden)

    Injac Rade

    2009-01-01

    Full Text Available Since the introduction of Doxorubicin (Dox for the treatment of cancer in 1969, this compound has demonstrated high antitumor efficacy. Dox's use in chemotherapy has been limited largely due to its diverse toxicities, including cardiac, liver, renal, pulmonary, hematological and testicular toxicity. Various attempts have been made to reduce Dox-induced toxicity. These include dosage optimization, synthesis and use of analogues. Moreover, a number of agents have been investigated as protective agents during Dox therapy. Polyhydroxilated derivatives of fullerene, named fullerenols C60(OHn, are being extensively studied due to their great potential as antioxidants. It is proposed that they might act as free radical scavengers in biological systems, in xenobiotics-induced oxidative stress as well as against radioactive irradiation. We have investigated the effects of fullerenol C60(OH24 (Frl at doses of 25, 50 and 100 mg kg-1 week (for a time-span of three weeks on heart and liver tissue after Doxorubicin (Dox-induced toxicity in rats with colorectal cancer. In the present study, in vivo Wistar male rat model was used to explore whether Frl could protect against Dox-induced (1.5 mg/kg/week for three weeks chronic cardio- and hepatotoxicity and compared the effect with a well-known antioxidant, vitamin C (100 mg/kg/week for three weeks. Commercially available methods were used for blood and pathohystological analysis and for the measurement of enzyme activity (SOD, MDA, GSH, GSSH, GPx, GR, CAT, CK, LDH, α-HBDH, AST, ALT in serum and homogenate samples of heart and liver tissues. According to macroscopic, microscopic, hematological, biochemical, physiological, pharmacological, and pharmacokinetic results, we confirmed that, at all examined doses, Frl exhibits a protective influence on the heart and liver tissue against chronic toxicity induced by Dox.

  13. Bacterial Toxicity and Metabolism of Three Hydrazine Fuels.

    Science.gov (United States)

    1980-09-01

    zine fuels have toxic effects on developing frog embryos and/or larvae. Hydrazine sulphate proved teratogenic at 40 milligrams per liter. MMH was...and for photographic developing . Hydrazine is also used as a surface active agent in plasticizer manufacturing (Reference 1). As of 1978, most...hour LC50 ranges for the common guppy of 0.6 to 4.6, 2.6 to 6.7, and 10.1 to 26.5 for hydrazine, MMH and UDMH, respectively. The range variation for

  14. 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

  15. DNA hypomethylation of CBS promoter induced by folate deficiency is a potential noninvasive circulating biomarker for colorectal adenocarcinomas.

    Science.gov (United States)

    Xue, Geng; Lu, Chao-Jing; Pan, Shu-Jun; Zhang, Yin-Ling; Miao, Hui; Shan, Shi; Zhu, Xiao-Ting; Zhang, Yi

    2017-08-01

    Aberrant DNA methylation patterns, which induced by folate deficiency, play important roles in tumorigenesis of colorectal cancer (CRC). Some DNA methylation alterations can also be detected in cell-free DNA (cfDNA) of patients' plasma, making cfDNA an ideal noninvasive circulating biomarker. However, exact DNA methylation alterations induced by folate deficiency in tumorigenesis of CRC and exact potential circulating cfDNA methylation biomarker are still unclear. Therefore, DNA methylation patterns of the normal human colon mucosal epithelial cell line (NCM460), cultured with normal or low folate content, were screened and the DNA hypomethylation of cystathionine-beta-synthase (CBS) promoter was further validated in vitro and vivo. Then, the correlation analysis between folate level, DNA methylation alteration in promoter and expression of CBS was carried out in vitro and vivo. Further, the methylation patterns of CBS promoter in plasma cfDNA were detected and statistically correlated with pathological parameters and clinical outcome. Our study showed that DNA hypomethylation in CBS promoter, induced by folate deficiency, would lead to up-regulation of CBS both in vitro and vivo. Patients with cfDNA hypomethylation of CBS promoter in plasma were correlated with high tumor stage and poor clinical outcome. In addition, cfDNA hypomethylation of CBS promoter in plasma was shown to be an independent prognostic factor for recurrence and cancer-related death in CRC. Our results indicated that DNA hypomethylation of CBS promoter induced by folate deficiency could serve as a potential noninvasive circulating biomarker and may be helpful in developing more effective prognostic markers for CRC.

  16. Oridonin induces apoptosis and senescence in colorectal cancer cells by increasing histone hyperacetylation and regulation of p16, p21, p27 and c-myc

    Directory of Open Access Journals (Sweden)

    Zhao Ying-Zheng

    2010-11-01

    Full Text Available Abstract Background Oridonin, a tetracycline diterpenoid compound, has the potential antitumor activities. Here, we evaluate the antitumor activity and action mechanisms of oridonin in colorectal cancer. Methods Effects of oridonin on cell proliferation were determined by using a CCK-8 Kit. Cell cycle distribution was determined by flow cytometry. Apoptosis was examined by analyzing subdiploid population and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assay. Senescent cells were determined by senescence-associated β-galactosidase activity analysis. Semi-quantitative RT-PCR was used to examine the changes of mRNA of p16, p21, p27 and c-myc. The concomitant changes of protein expression were analyzed with Western blot. Expression of AcH3 and AcH4 were examined by immunofluorescence staining and Western blots. Effects of oridonin on colony formation of SW1116 were examined by Soft Agar assay. The in vivo efficacy of oridonin was detected using a xenograft colorectal cancer model in nude mice. Results Oridonin induced potent growth inhibition, cell cycle arrest, apoptosis, senescence and colony-forming inhibition in three colorectal cancer cell lines in a dose-dependent manner in vitro. Daily i.p. injection of oridonin (6.25, 12.5 or 25 mg/kg for 28 days significantly inhibited the growth of SW1116 s.c. xenografts in BABL/C nude mice. With western blot and reverse transcription-PCR, we further showed that the antitumor activities of oridonin correlated with induction of histone (H3 and H4 hyperacetylation, activation of p21, p27 and p16, and suppression of c-myc expression. Conclusion Oridonin possesses potent in vitro and in vivo anti-colorectal cancer activities that correlated with induction of histone hyperacetylation and regulation of pathways critical for maintaining growth inhibition and cell cycle arrest. Therefore, oridonin may represent a novel therapeutic option in colorectal cancer treatment.

  17. Synthesis and Free Radical Scavenging Activity of New Hydroxybenzylidene Hydrazines

    National Research Council Canada - National Science Library

    Frantisek Sersen; Fridrich Gregan; Peter Kotora; Jarmila Kmetova; Juraj Filo; Dusan Loos; Juraj Gregan

    2017-01-01

    Hydroxybenzylidene hydrazines exhibit a wide spectrum of biological activities. Here, we report synthesis and free radical scavenging activity of nine new N-(hydroxybenzylidene)-N′-[2,6-dinitro-4-(trifluoromethyl)]phenylhydrazines...

  18. Enthalpy of Formation of N2H4 (Hydrazine) Revisited

    Energy Technology Data Exchange (ETDEWEB)

    Feller, David; Bross, David H.; Ruscic, Branko

    2017-08-17

    In order to address the accuracy of the long-standing experimental enthalpy of formation of gas-phase hydrazine, fully confirmed in earlier versions of Active Thermochemical Tables (ATcT), the provenance of that value is re-examined in light of new high-end calculations of the Feller-Peterson-Dixon (FPD) variety. An overly optimistic determination of the vaporization enthalpy of hydrazine, which created an unrealistically strong connection between the gas phase thermochemistry and the calorimetric results defining the thermochemistry of liquid hydrazine was identified as the probable culprit. The new enthalpy of formation of gas-phase hydrazine, based on balancing all available knowledge, was determined to be 111.57 ± 0.47 kJ/mol at 0 K (97.41 kJ/mol at 298.15 K). Close agreement was found between the ATcT (even excluding the latest theoretical result) and FPD enthalpies.

  19. Mobility Spectrometer Studies on Hydrazine and Ammonia Detection

    Science.gov (United States)

    Niu, William; Eiceman, Gary; Szumlas, Andrew; Lewis, John

    2011-01-01

    An airborne vapor analyzer for detecting sub- to low- parts-per-million (ppm) hydrazine in the presence of higher concentration levels of ammonia has been under development for the Orion program. The detector is based on ambient pressure ionization and ion mobility characterization. The detector encompasses: 1) a membrane inlet to exclude particulate and aerosols from the analyzer inlet; 2) a method to separate hydrazine from ammonia which would otherwise lead to loss of calibration and quantitative accuracy for the hydrazine determination; and 3) response and quantitative determinations for both hydrazine and ammonia. Laboratory studies were made to explore some of these features including mobility measurements mindful of power, size, and weight issues. The study recommended the use of a mobility spectrometer of traditional design with a reagent gas and equipped with an inlet transfer line of bonded phase fused silica tube. The inlet transfer line provided gas phase separation of neutrals of ammonia from hydrazine at 50 C simplifying significantly the ionization chemistry that underlies response in a mobility spectrometer. Performance of the analyzer was acceptable between ranges of 30 to 80 C for both the pre-fractionation column and the drift tube. An inlet comprised of a combined membrane with valve-less injector allowed high speed quantitative determination of ammonia and hydrazine without cross reactivity from common metabolites such as alcohols, esters, and aldehydes. Preliminary test results and some of the design features are discussed.

  20. The different radiation response and radiation-induced bystander effects in colorectal carcinoma cells differing in p53 status.

    Science.gov (United States)

    Widel, Maria; Lalik, Anna; Krzywon, Aleksandra; Poleszczuk, Jan; Fujarewicz, Krzysztof; Rzeszowska-Wolny, Joanna

    2015-08-01

    Radiation-induced bystander effect, appearing as different biological changes in cells that are not directly exposed to ionizing radiation but are under the influence of molecular signals secreted by irradiated neighbors, have recently attracted considerable interest due to their possible implication for radiotherapy. However, various cells present diverse radiosensitivity and bystander responses that depend, inter alia, on genetic status including TP53, the gene controlling the cell cycle, DNA repair and apoptosis. Here we compared the ionizing radiation and bystander responses of human colorectal carcinoma HCT116 cells with wild type or knockout TP53 using a transwell co-culture system. The viability of exposed to X-rays (0-8 Gy) and bystander cells of both lines showed a roughly comparable decline with increasing dose. The frequency of micronuclei was also comparable at lower doses but at higher increased considerably, especially in bystander TP53-/- cells. Moreover, the TP53-/- cells showed a significantly elevated frequency of apoptosis, while TP53+/+ counterparts expressed high level of senescence. The cross-matched experiments where irradiated cells of one line were co-cultured with non-irradiated cells of opposite line show that both cell lines were also able to induce bystander effects in their counterparts, however different endpoints revealed with different strength. Potential mediators of bystander effects, IL-6 and IL-8, were also generated differently in both lines. The knockout cells secreted IL-6 at lower doses whereas wild type cells only at higher doses. Secretion of IL-8 by TP53-/- control cells was many times lower than that by TP53+/+ but increased significantly after irradiation. Transcription of the NFκBIA was induced in irradiated TP53+/+ mainly, but in bystanders a higher level was observed in TP53-/- cells, suggesting that TP53 is required for induction of NFκB pathway after irradiation but another mechanism of activation must operate in

  1. Colorectal distention induces acute and delayed visceral hypersensitivity: role of peripheral corticotropin-releasing factor and interleukin-1 in rats.

    Science.gov (United States)

    Nozu, Tsukasa; Kumei, Shima; Miyagishi, Saori; Takakusaki, Kaoru; Okumura, Toshikatsu

    2015-12-01

    Most studies evaluating visceral sensation measure visceromotor response (VMR) to colorectal distention (CRD). However, CRD itself induces visceral sensitization, and little is known about the detailed characteristics of this response. The present study tried to clarify this question. VMR was determined by measuring abdominal muscle contractions as a response to CRD in rats. The CRD set consisted of two isobaric distentions (60 mmHg for 10 min twice, with a 30-min rest), and the CRD set was performed on two separate days, i.e., days 1 and 3, 8. On day 1, VMR to the second CRD was increased as compared with that to the first CRD, which is the acute sensitization. VMR to the first CRD on day 3 returned to the same level as that to the first CRD on day 1, and total VMR, i.e., the whole response to the CRD set, was not different between day 1 and day 3. However, total VMR was significantly increased on day 8 as compared with that on day 1, suggesting CRD induced the delayed sensitization. Intraperitoneally administered astressin (200 µg/kg), a corticotropin-releasing factor receptor antagonist, at the end of the first CRD blocked the acute sensitization, but anakinra (20 mg/kg, intraperitoneally), an interleukin-1 receptor antagonist, did not modify it. Astressin (200 µg/kg, twice before CRD on day 8) did not alter the delayed sensitization, but anakinra (20 mg/kg, twice) abolished it. CRD induced both acute sensitization and delayed sensitization, which were mediated through peripheral corticotropin-releasing factor and interleukin-1 pathways, respectively.

  2. DDX3 enhances oncogenic KRAS‑induced tumor invasion in colorectal cancer via the β‑catenin/ZEB1 axis.

    Science.gov (United States)

    Wu, De-Wei; Lin, Po-Lin; Cheng, Ya-Wen; Huang, Chi-Chou; Wang, Lee; Lee, Huei

    2016-04-19

    DDX3 plays a dual role in colorectal cancer; however, the role and underlying mechanism of DDX3 in colorectal tumorigenesis remains unclear. Here, we provide evidence that DDX3 enhances oncogenic KRAS transcription via an increase in SP1 binding to its promoter. Accelerating oncogenic KRAS expression by DDX3 promotes the invasion capability via the ERK/PTEN/AKT/β-catenin cascade. Moreover, the β-catenin/ZEB1 axis is responsible for DDX3-induced cell invasiveness and xenograft lung tumor nodule formation. The xenograft lung tumor nodules induced by DDX3-overexpressing T84 stable clone were nearly suppressed by the inhibitor of AKT (perifosine) or β-catenin (XAV939). Among patients, high KRAS, positive nuclear β-catenin expression and high ZEB1 were more commonly occurred in high-DDX3 tumors than in low-DDX3 tumors. High-DDX3, high-KRAS, positive nuclear β-catenin tumors, and high-ZEB1 exhibited worse overall survival (OS) and relapse free survival (RFS) than their counterparts. In conclusion, DDX3 may play an oncogenic role to promote tumor growth and invasion in colon cancer cells via the β-catenin/ZEB1 axis due to increasing KRAS transcription. We therefore suggest that AKT or β-catenin may potentially act as a therapeutic target to improve tumor regression and outcomes in colorectal cancer patients who harbored high-DDX3 tumors.

  3. Improved Activation toward Primary Colorectal Cancer Cells by Antigen-Specific Targeting Autologous Cytokine-Induced Killer Cells

    Directory of Open Access Journals (Sweden)

    Claudia Schlimper

    2012-01-01

    Full Text Available Adoptive therapy of malignant diseases with cytokine-induced killer (CIK cells showed promise in a number of trials; the activation of CIK cells from cancer patients towards their autologous cancer cells still needs to be improved. Here, we generated CIK cells ex vivo from blood lymphocytes of colorectal cancer patients and engineered those cells with a chimeric antigen receptor (CAR with an antibody-defined specificity for carcinoembryonic antigen (CEA. CIK cells thereby gained a new specificity as defined by the CAR and showed increase in activation towards CEA+ colon carcinoma cells, but less in presence of CEA− cells, indicated by increased secretion of proinflammatory cytokines. Redirected CIK activation was superior by CAR-mediated CD28-CD3ζ than CD3ζ signaling only. CAR-engineered CIK cells from colon carcinoma patients showed improved activation against their autologous, primary carcinoma cells from biopsies resulting in more efficient tumour cell lysis. We assume that adoptive therapy with CAR-modified CIK cells shows improved selectivity in targeting autologous tumour lesions.

  4. Scorpion (Androctonus bicolor venom exhibits cytotoxicity and induces cell cycle arrest and apoptosis in breast and colorectal cancer cell lines

    Directory of Open Access Journals (Sweden)

    Abdulrahman K Al-Asmari

    2016-01-01

    Full Text Available Objectives: The defective apoptosis is believed to play a major role in the survival and proliferation of neoplastic cells. Hence, the induction of apoptosis in cancer cells is one of the targets for cancer treatment. Researchers are considering scorpion venom as a potent natural source for cancer treatment because it contains many bioactive compounds. The main objective of the current study is to evaluate the anticancer property of Androctonus bicolor scorpion venom on cancer cells. Materials and Methods: Scorpions were milked by electrical stimulation of telsons and lyophilized. The breast (MDA-MB-231 and colorectal (HCT-8 cancer cells were maintained in appropriate condition. The venom cytotoxicity was assessed by 3-(4,5-di-methylthiazol-2-yl-2,5-diphenyl-2H-tetrazolium bromide assay, and the cellular and nuclear changes were studied with propidium iodide and 4′,6-diamidino-2-phenylindole stain, respectively. The cell cycle arrest was examined using muse cell analyzer. Results: The A. bicolor venom exerted cytotoxic effects on MDA-MB-231 and HCT-8 cells in a dose- and duration-dependent manner and induced apoptotic cell death. The treatment with this venom arrests the cancer cells in G0/G1 phase of cell cycle. Conclusions: The venom selectively induces the rate of apoptosis in MDA-MB-231 and HCT-8 cells as reflected by morphological and cell cycle studies. To the best of our knowledge, this is the first scientific evidence demonstrating the induction of apoptosis and cell cycle arrest by A. bicolor scorpion venom.

  5. Scorpion (Androctonus bicolor) venom exhibits cytotoxicity and induces cell cycle arrest and apoptosis in breast and colorectal cancer cell lines

    Science.gov (United States)

    Al-Asmari, Abdulrahman K.; Riyasdeen, Anvarbatcha; Abbasmanthiri, Rajamohamed; Arshaduddin, Mohammed; Al-Harthi, Fahad Ali

    2016-01-01

    Objectives: The defective apoptosis is believed to play a major role in the survival and proliferation of neoplastic cells. Hence, the induction of apoptosis in cancer cells is one of the targets for cancer treatment. Researchers are considering scorpion venom as a potent natural source for cancer treatment because it contains many bioactive compounds. The main objective of the current study is to evaluate the anticancer property of Androctonus bicolor scorpion venom on cancer cells. Materials and Methods: Scorpions were milked by electrical stimulation of telsons and lyophilized. The breast (MDA-MB-231) and colorectal (HCT-8) cancer cells were maintained in appropriate condition. The venom cytotoxicity was assessed by 3-(4,5-di-methylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide assay, and the cellular and nuclear changes were studied with propidium iodide and 4’,6-diamidino-2-phenylindole stain, respectively. The cell cycle arrest was examined using muse cell analyzer. Results: The A. bicolor venom exerted cytotoxic effects on MDA-MB-231 and HCT-8 cells in a dose- and duration-dependent manner and induced apoptotic cell death. The treatment with this venom arrests the cancer cells in G0/G1 phase of cell cycle. Conclusions: The venom selectively induces the rate of apoptosis in MDA-MB-231 and HCT-8 cells as reflected by morphological and cell cycle studies. To the best of our knowledge, this is the first scientific evidence demonstrating the induction of apoptosis and cell cycle arrest by A. bicolor scorpion venom. PMID:27721540

  6. Curcumol Inhibits Growth and Induces Apoptosis of Colorectal Cancer LoVo Cell Line via IGF-1R and p38 MAPK Pathway.

    Science.gov (United States)

    Wang, Juan; Huang, Fengxiang; Bai, Zhun; Chi, Bixia; Wu, Jiacai; Chen, Xu

    2015-08-20

    Curcumol, isolated from the traditional medical plant Rhizoma Curcumae, is the bioactive component of Zedoary oil, whose potential anti-tumor effect has attracted considerable attention in recent years. Though many researchers have reported curcumol and its bioactivity, the potential molecular mechanism for its anti-cancer effect in colorectal cancer LoVo cells still remains unclear. In the present study, we found that curcumol showed growth inhibition and induced apoptosis of LoVo cells in a dose- and time-dependent manner. The occurrence of its proliferation inhibition and apoptosis came with suppression of IGF-1R expression, and then increased the phosphorylation of p38 mitogen activated protein kinase (MAPK), which might result in a cascade response by inhibiting the CREB survival pathway and finally triggered Bax/Bcl-2 and poly(ADP-ribose) polymerase 1 (PARP-1) apoptosis signals. Moreover, curcumol inhibited colorectal cancer in xenograft models of nude mice. Immunohistochemical and Western blot analysis revealed that curcumol could decrease the expression of ki-67, Bcl-2 as well as CREB1, and increase the expression of Bax and the phosphorylation of p38, which were consistent with our in vitro study. Overall, our in vitro and in vivo data confirmed the anti-cancer activity of curcumol, which was related to a significant inhibition of IGF-1R and activation of p38 MAPKs, indicating that curcumol may be a potential anti-tumor agent for colorectal carcinoma therapy.

  7. Curcumol Inhibits Growth and Induces Apoptosis of Colorectal Cancer LoVo Cell Line via IGF-1R and p38 MAPK Pathway

    Directory of Open Access Journals (Sweden)

    Juan Wang

    2015-08-01

    Full Text Available Curcumol, isolated from the traditional medical plant Rhizoma Curcumae, is the bioactive component of Zedoary oil, whose potential anti-tumor effect has attracted considerable attention in recent years. Though many researchers have reported curcumol and its bioactivity, the potential molecular mechanism for its anti-cancer effect in colorectal cancer LoVo cells still remains unclear. In the present study, we found that curcumol showed growth inhibition and induced apoptosis of LoVo cells in a dose- and time-dependent manner. The occurrence of its proliferation inhibition and apoptosis came with suppression of IGF-1R expression, and then increased the phosphorylation of p38 mitogen activated protein kinase (MAPK, which might result in a cascade response by inhibiting the CREB survival pathway and finally triggered Bax/Bcl-2 and poly(ADP-ribose polymerase 1 (PARP-1 apoptosis signals. Moreover, curcumol inhibited colorectal cancer in xenograft models of nude mice. Immunohistochemical and Western blot analysis revealed that curcumol could decrease the expression of ki-67, Bcl-2 as well as CREB1, and increase the expression of Bax and the phosphorylation of p38, which were consistent with our in vitro study. Overall, our in vitro and in vivo data confirmed the anti-cancer activity of curcumol, which was related to a significant inhibition of IGF-1R and activation of p38 MAPKs, indicating that curcumol may be a potential anti-tumor agent for colorectal carcinoma therapy.

  8. 6-Bromoisatin Found in Muricid Mollusc Extracts Inhibits Colon Cancer Cell Proliferation and Induces Apoptosis, Preventing Early Stage Tumor Formation in a Colorectal Cancer Rodent Model

    Directory of Open Access Journals (Sweden)

    Babak Esmaeelian

    2013-12-01

    Full Text Available Muricid molluscs are a natural source of brominated isatin with anticancer activity. The aim of this study was to examine the safety and efficacy of synthetic 6-bromoisatin for reducing the risk of early stage colorectal tumor formation. The purity of 6-bromoisatin was confirmed by 1H NMR spectroscopy, then tested for in vitro and in vivo anticancer activity. A mouse model for colorectal cancer was utilized whereby colonic apoptosis and cell proliferation was measured 6 h after azoxymethane treatment by hematoxylin and immunohistochemical staining. Liver enzymes and other biochemistry parameters were measured in plasma and haematological assessment of the blood was conducted to assess potential toxic side-effects. 6-Bromoisatin inhibited proliferation of HT29 cells at IC50 223 μM (0.05 mg/mL and induced apoptosis without increasing caspase 3/7 activity. In vivo 6-bromoisatin (0.05 mg/g was found to significantly enhance the apoptotic index (p ≤ 0.001 and reduced cell proliferation (p ≤ 0.01 in the distal colon. There were no significant effects on mouse body weight, liver enzymes, biochemical factors or blood cells. However, 6-bromoisatin caused a decrease in the plasma level of potassium, suggesting a diuretic effect. In conclusion this study supports 6-bromoisatin in Muricidae extracts as a promising lead for prevention of colorectal cancer.

  9. Hydrazine Borane and Hydrazinidoboranes as Chemical Hydrogen Storage Materials

    Directory of Open Access Journals (Sweden)

    Romain Moury

    2015-04-01

    Full Text Available Hydrazine borane N2H4BH3 and alkali derivatives (i.e., lithium, sodium and potassium hydrazinidoboranes MN2H3BH3 with M = Li, Na and K have been considered as potential chemical hydrogen storage materials. They belong to the family of boron- and nitrogen-based materials and the present article aims at providing a timely review while focusing on fundamentals so that their effective potential in the field could be appreciated. It stands out that, on the one hand, hydrazine borane, in aqueous solution, would be suitable for full dehydrogenation in hydrolytic conditions; the most attractive feature is the possibility to dehydrogenate, in addition to the BH3 group, the N2H4 moiety in the presence of an active and selective metal-based catalyst but for which further improvements are still necessary. However, the thermolytic dehydrogenation of hydrazine borane should be avoided because of the evolution of significant amounts of hydrazine and the formation of a shock-sensitive solid residue upon heating at >300 °C. On the other hand, the alkali hydrazinidoboranes, obtained by reaction of hydrazine borane with alkali hydrides, would be more suitable to thermolytic dehydrogenation, with improved properties in comparison to the parent borane. All of these aspects are surveyed herein and put into perspective.

  10. Phase II/III Study of Radiofrequency Ablation Combined with Cytokine-Induced Killer Cells Treating Colorectal Liver Metastases

    Directory of Open Access Journals (Sweden)

    Xiaodong Li

    2016-11-01

    Full Text Available Purpose: This phase II/III, non-randomized clinical trial aimed to determine the efficacy and safety of the combination of radiofrequency ablation (RFA and cytokine-induced killer (CIK cells transfusion for patients with colorectal liver metastases (CRLMs. Experimental Design: A total of 60 eligible patients with CRLMs were enrolled and divided into Group A (RFA alone, n = 30 and Group B (RFA plus CIK, n = 30, and following enzyme-linked immunosorbent spot assay was performed in 8 patients with CEA > 50 ng/mL pre-RFA and 7 days post-RFA and CIK treatment, respectively. Results: The median progression-free survival (PFS times of Group A and Group B were 18.5 months and 23 months, respectively (P = 0.0336. The 3-year progression-free rates were 13.3% in Group A and 20.3% in Group B, respectively. The median overall survival time was 43 months in Group A, and not reached in Group B. The 3-year survival rates were 64.6% in Group A and 81.0% in Group B, respectively (P = 0.1187. Among the 8 patients with CEA > 50ng/mL, 6 had increase of circulating CEA-specific T cells after RFA (P = 0.010. After CIK cell therapy, the number of CEA-specific T cells increased in all the 8 patients comparing with that pre-treatment (P = 0.001 and in 7 patients comparing with that post-RFA (P = 0.028. Conclusions: We firstly confirm that the combination of RFA and CIK cells boosts CEA-specific T cell response and shows to be an efficacious and safe treatment modality for patients with CRLMs.

  11. The different radiation response and radiation-induced bystander effects in colorectal carcinoma cells differing in p53 status

    Energy Technology Data Exchange (ETDEWEB)

    Widel, Maria, E-mail: maria.widel@polsl.pl [Biosystems Group, Institute of Automatic Control, Silesian University of Technology, 16 Akademicka Street, 44-100 Gliwice (Poland); Lalik, Anna; Krzywon, Aleksandra [Biosystems Group, Institute of Automatic Control, Silesian University of Technology, 16 Akademicka Street, 44-100 Gliwice (Poland); Poleszczuk, Jan [College of Inter-faculty Individual Studies in Mathematics and Natural Sciences, University of Warsaw, 93 Zwirki i Wigury Street, 02-089 Warsaw (Poland); Department of Integrated Mathematical Oncology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, Florida (United States); Fujarewicz, Krzysztof; Rzeszowska-Wolny, Joanna [Biosystems Group, Institute of Automatic Control, Silesian University of Technology, 16 Akademicka Street, 44-100 Gliwice (Poland)

    2015-08-15

    Highlights: • We tested radiation response and bystander effect on HCT116p53+/+ and p53−/− cells. • The p53+/+ cells developed premature senescence in exposed and bystander neighbors. • Directly exposed and bystander p53−/− cells died profoundly through apoptosis. • Interleukins 6 and 8 were differently generated by both cell lines. • NFκB path was activated mainly in p53+/+ hit cells, in p53 −/− in bystanders only. - Abstract: Radiation-induced bystander effect, appearing as different biological changes in cells that are not directly exposed to ionizing radiation but are under the influence of molecular signals secreted by irradiated neighbors, have recently attracted considerable interest due to their possible implication for radiotherapy. However, various cells present diverse radiosensitivity and bystander responses that depend, inter alia, on genetic status including TP53, the gene controlling the cell cycle, DNA repair and apoptosis. Here we compared the ionizing radiation and bystander responses of human colorectal carcinoma HCT116 cells with wild type or knockout TP53 using a transwell co-culture system. The viability of exposed to X-rays (0–8 Gy) and bystander cells of both lines showed a roughly comparable decline with increasing dose. The frequency of micronuclei was also comparable at lower doses but at higher increased considerably, especially in bystander TP53-/- cells. Moreover, the TP53-/- cells showed a significantly elevated frequency of apoptosis, while TP53+/+ counterparts expressed high level of senescence. The cross-matched experiments where irradiated cells of one line were co-cultured with non-irradiated cells of opposite line show that both cell lines were also able to induce bystander effects in their counterparts, however different endpoints revealed with different strength. Potential mediators of bystander effects, IL-6 and IL-8, were also generated differently in both lines. The knockout cells secreted IL-6 at

  12. 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

    2012-10-01

    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 (Pcolons of obese 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. Copyright © 2012 Elsevier Inc. All rights reserved.

  13. Inositol hexaphosphate suppresses growth and induces apoptosis in HT-29 colorectal cancer cells in culture: PI3K/Akt pathway as a potential target.

    Science.gov (United States)

    Liu, Guiyuan; Song, Yang; Cui, Lianhua; Wen, Zhaoxia; Lu, Xiaoqing

    2015-01-01

    Inositol hexaphosphate (IP6) is a polyphosphorylated carbohydrate that is present in high amounts in almost all plants and mammalian cells. IP6 induces apoptosis in multiple types of cancer cells, including prostate cancer, breast cancer, skin tumor, liver cancer and colorectal cancer. However, little is known regarding the molecular mechanisms of its anticancer effects. Therefore, this study was conducted to investigate the activity of IP6 against human colorectal cancer cells (HT-29) and to determine whether the IP6 regulates apoptosis in HT-29 cells by inhibiting the PI3K/Akt signaling pathway. A human colorectal cancer cell line (HT-29) was used for the study. HT-29 cells were treated with 0, 50, 100, 200, and 400 μg/mL of IP6. The MTT colorimetric assay was used to observe the proliferation of HT-29 in vitro, and flow cytometry (FCM) was used to analyze the apoptosis of the HT-29 cells. The relative mRNA expression was determined by real-time PCR, and relative protein levels were analyzed by Western blot analysis. The results of MTT showed that HT-29 cells underwent inhibition of proliferation after exposure to IP6 (100-400 μg/mL) for 12 and 48 h, and this inhibition clearly relied on time and dosage. IP6 induced apoptosis in HT-29 cells in a dose-dependent manner. The mRNA and protein expression of PI3K and Akt decreased in the groups treated with IP6, and IP6 inhibited the phosphorylation of Akt (pAkt), whereas increased the expression of its downstream effector, caspase-9. Our results suggested that by targeting PI3K/Akt pathway, IP6 suppresses cell survival and proliferation, but induces death in HT-29 cells.

  14. KCNN4 channels participate in the EMT induced by PRL-3 in colorectal cancer.

    Science.gov (United States)

    Lai, Wei; Liu, Lu; Zeng, Yujie; Wu, Heng; Xu, Heyang; Chen, Shuang; Chu, Zhonghua

    2013-01-01

    Studies have shown that phosphatase of regenerating liver-3 (PRL-3) promotes the invasion, migration, and metastasis of human tumor cells by facilitating an epithelial-mesenchymal transition (EMT). However, the mechanism by which PRL-3 induces tumor cell EMT is unknown. Our previous research revealed that PRL-3 promotes LoVo cell proliferation by up-regulating KCNN4 channels. In the current study, we explored the mechanism by which PRL-3 mediates EMT. We demonstrated that PRL-3 induced the expression of KCNN4 channels, leading to EMT and the down-regulation of E-cadherin. Further studies revealed that KCNN4 channels increased intracellular calcium levels and activated components of cell signaling downstream of calcium, including CaM-kinase II and glycogen synthase kinase-3 beta (GSK-3 beta), which increased Snail expression. Inhibiting KCNN4 with siRNA and TRAM-34, a specific inhibitor, restored E-cadherin expression and inhibited Snail expression. These results implicated the up-regulation of KCNN4 channels in the PRL-3-mediated induction of EMT and promotion of cancer metastasis.

  15. Violacein synergistically increases 5-fluorouracil cytotoxicity, induces apoptosis and inhibits Akt-mediated signal transduction in human colorectal cancer cells

    NARCIS (Netherlands)

    Kodach, LL; Bos, CL; Duran, N; Peppelenbosch, MP; Ferreira, CV; Hardwick, JCH

    2006-01-01

    Despite recent additions to the armory of chemotherapeutic agents for colorectal cancer (CRC) treatment, the results of chemotherapy remain unsatisfactory. 5-Fluorouracil (5-FU) still represents the cornerstone of treatment and resistance to its actions is a major obstacle to successful chemotherapy

  16. Tests for Colorectal Cancer

    Science.gov (United States)

    ... Cancer Early Detection, Diagnosis, and Staging Tests for Colorectal Cancer Colorectal cancer is often found after symptoms appear, ... Report: Colon Pathology. Imaging tests to look for colorectal cancer Imaging tests use sound waves, x-rays, magnetic ...

  17. Echinacoside Induces Apoptosis in Human SW480 Colorectal Cancer Cells by Induction of Oxidative DNA Damages

    Directory of Open Access Journals (Sweden)

    Liwei Dong

    2015-06-01

    Full Text Available Echinacoside is a natural compound with potent reactive oxygen species (ROS-scavenging and anti-oxidative bioactivities, which protect cells from oxidative damages. As cancer cells are often under intense oxidative stress, we therefore tested if Echinacoside treatment would promote cancer development. Surprisingly, we found that Echinacoside significantly inhibited the growth and proliferation of a panel of cancer cell lines. Treatment of the human SW480 cancer cells with Echinacoside resulted in marked apoptosis and cell cycle arrest, together with a significant increase in active caspase 3 and cleaved PARP, and upregulation of the G1/S-CDK blocker CDKN1B (p21. Interestingly, immunocytochemistry examination of drug-treated cancer cells revealed that Echinacoside caused a significant increase of intracellular oxidized guanine, 8-oxoG, and dramatic upregulation of the double-strand DNA break (DSB-binding protein 53BP1, suggesting that Echinacoside induced cell cycle arrest and apoptosis in SW480 cancer cells via induction of oxidative DNA damages. These results establish Echinacoside as a novel chemical scaffold for development of anticancer drugs.

  18. MC37, a new mono-carbonyl curcumin analog, induces G2/M cell cycle arrest and mitochondria-mediated apoptosis in human colorectal cancer cells.

    Science.gov (United States)

    Liang, Baoxia; Liu, Ziyi; Cao, Yingnan; Zhu, Cuige; Zuo, Yinglin; Huang, Lei; Wen, Gesi; Shang, Nana; Chen, Yu; Yue, Xin; Du, Jun; Li, Baojian; Zhou, Binhua; Bu, Xianzhang

    2017-02-05

    (E)-1-(3'-fluoro-[1,1'-biphenyl-3-yl)-3-(3-hydroxy-4-methoxyphenyl)prop-2-en-1-one) (MC37), a novel mono-carbonyl curcumin analog, was previously synthesized in our laboratory as a nuclear factor kappa B (NF-κB) inhibitor with excellent cytotoxicity against several cancer cell lines. In this study, our further investigations showed that the potent growth inhibitory activity of MC37 in human colorectal cancer cells was associated with the arrest of cell cycle progression and the induction of apoptosis. As a multi-targeted agent, MC37 inhibited the intracellular microtubule assembly, altered the expression of cyclin-dependent kinase 1 (CDK1), and ultimately induced G2/M cell cycle arrest. Moreover, MC37 collapsed the mitochondrial membrane potential (MMP), increased the Bax/Bcl-2 ratio, activated the caspase-9/3 cascade, and finally led to cancer cells apoptosis, suggesting that the mitochondrial-mediated apoptotic pathway was involved in MC37-induced apoptosis. In conclusion, these observations demonstrated that mono-carbonyl curcumin analogs would serve as multi-targeted lead for promising anti-colorectal cancer agent development. Copyright © 2016 Elsevier B.V. All rights reserved.

  19. Tomato powder impedes the development of azoxymethane-induced colorectal cancer in rats through suppression of COX-2 expression via NF-κB and regulating Nrf2/HO-1 pathway.

    Science.gov (United States)

    Tuzcu, Mehmet; Aslan, Abdullah; Tuzcu, Zeynep; Yabas, Mehmet; Bahcecioglu, Ibrahim Halil; Ozercan, Ibrahim Hanifi; Kucuk, Omer; Sahin, Kazim

    2012-09-01

    Cancer is one of the leading causes of death worldwide. Since dietary factors have been connected to a reduced risk of a diversity of human cancers, in this study we investigated the effects of tomato powder (TP) on the development of azoxymethane (AOM)-induced colorectal cancer in Wistar rats, and possible mechanism(s) by which TP shows its chemopreventive activity. Here we show that TP added to feed at 5% rate decreases the rate of aberrant crypt foci (ACF) and reduces the development of adenocarcinoma and growth of AOM-induced colorectal cancer in rats. In addition, we demonstrate that TP supplementation shows its chemopreventive activities through inhibition of cyclooxygenase-2 (COX-2) expression via NF-κB pathway and promotion of apoptosis, as well as regulating Nrf2/HO-1 signaling pathway in colorectal tissue of AOM-treated rats. Our findings identify an intimate connection between dietary supplementation of TP and the decreased risk of colorectal cancer in rats, and suggest that consumption of TP would be a natural candidate for the prevention of colorectal cancer in men.

  20. ent-kaurane diterpenoids from Croton tonkinensis induce apoptosis in colorectal cancer cells through the phosphorylation of JNK mediated by reactive oxygen species and dual-specificity JNK kinase MKK4.

    Science.gov (United States)

    Thuong, Phuong Thien; Khoi, Nguyen Minh; Ohta, Saho; Shiota, Shinichiro; Kanta, Hironori; Takeuchi, Kenji; Ito, Fumiaki

    2014-01-01

    To search for new chemotherapeutic agents to treat colorectal cancer, we isolated a number of natural ent-kaurane diterpenoids from the plant Croton tonkinensis. Among them, only CeKDs with the 15-oxo-16-ene moiety induced the apoptosis of colorectal cancer cell lines Caco-2 and LS180. The active CeKD induced the activation of ERK and JNK, but the inactive ones induced that of ERK, but not that of JNK. It thus appears that JNK seemed to play an important role in the apoptotic activity of the active compounds. The dualspecificity JNK kinase MKK4 was activated in both colorectal cancer cells treated with the active CeKD, but MKK7 was not activated. Further, the active CeKD, but not the inactive one, enhanced the generation of intracellular reactive oxygen species (ROS) in both cells. CeKD-induced cell apoptosis and ROS generation, as well as JNK activation, were inhibited by the antioxidant N-acetyl-L-cysteine. These findings suggest that ROS stimulated the phosphorylation of JNK mediated by MKK4 and played a critical role in CeKD-induced apoptosis in colorectal cancer cells.

  1. Ultraviolet surface plasmon-mediated low temperature hydrazine decomposition

    Energy Technology Data Exchange (ETDEWEB)

    Peng, Siying; Sheldon, Matthew T.; Atwater, Harry A. [Thomas J. Watson Laboratories of Applied Physics, California Institute of Technology, Pasadena, California 91125 (United States); Liu, Wei-Guang; Jaramillo-Botero, Andres; Goddard, William Andrew [Materials and Process Simulation Center, California Institute of Technology, Pasadena, California 91125 (United States)

    2015-01-12

    Conventional methods require elevated temperatures in order to dissociate high-energy nitrogen bonds in precursor molecules such as ammonia or hydrazine used for nitride film growth. We report enhanced photodissociation of surface-absorbed hydrazine (N{sub 2}H{sub 4}) molecules at low temperature by using ultraviolet surface plasmons to concentrate the exciting radiation. Plasmonic nanostructured aluminum substrates were designed to provide resonant near field concentration at λ = 248 nm (5 eV), corresponding to the maximum optical cross section for hydrogen abstraction from N{sub 2}H{sub 4}. We employed nanoimprint lithography to fabricate 1 mm × 1 mm arrays of the resonant plasmonic structures, and ultraviolet reflectance spectroscopy confirmed resonant extinction at 248 nm. Hydrazine was cryogenically adsorbed to the plasmonic substrate in a low-pressure ambient, and 5 eV surface plasmons were resonantly excited using a pulsed KrF laser. Mass spectrometry was used to characterize the photodissociation products and indicated a 6.2× overall enhancement in photodissociation yield for hydrazine adsorbed on plasmonic substrates compared with control substrates. The ultraviolet surface plasmon enhanced photodissociation demonstrated here may provide a valuable method to generate reactive precursors for deposition of nitride thin film materials at low temperatures.

  2. Neoadjuvant TACE before laser induced thermotherapy (LITT) in the treatment of non-colorectal non-breast cancer liver metastases: Feasibility and survival rates

    Energy Technology Data Exchange (ETDEWEB)

    Vogl, Thomas J., E-mail: T.Vogl@em.uni-frankfurt.de [Institute for Diagnostic and Interventional Radiology, Johann Wolfgang Goethe-University Frankfurt (Germany); Kreutzträger, Martin; Gruber-Rouh, Tatjana; Eichler, Katrin [Institute for Diagnostic and Interventional Radiology, Johann Wolfgang Goethe-University Frankfurt (Germany); Nour-Eldin, Nour-Eldin A. [Institute for Diagnostic and Interventional Radiology, Johann Wolfgang Goethe-University Frankfurt (Germany); Department of Diagnostic and Interventional Radiology, Cairo University, Cairo (Egypt); Zangos, Stephan [Institute for Diagnostic and Interventional Radiology, Johann Wolfgang Goethe-University Frankfurt (Germany); Naguib, Nagy N.N. [Institute for Diagnostic and Interventional Radiology, Johann Wolfgang Goethe-University Frankfurt (Germany); Department of Radiology, Faculty of Medicine, Alexandria University, Alexandria (Egypt)

    2014-10-15

    Purpose: To evaluate safety, feasibility and overall survival rates for transarterial chemoembolization (TACE) alone or combined with MR-guided laser-induced-thermotherapy (LITT) in liver metastases of non-colorectal and non-breast cancer origin. Methods and materials: Included were patients with unresectable non-colorectal non-breast cancer liver metastases with progression under systemic chemotherapy. Excluded were patients with Karnofsky score ≤70, respiratory, renal and cardiovascular failure, and general TACE contraindications. TACE using Mitomycin alone, Mitomycin–Gemcitabine or Mitomycin–Gemcitabine–Cisplatin was performed to all patients. After TACE 146 metastases were ablated with MR-guided LITT. To be eligible for LITT metastases should be <5 cm in size and ≤5 in number. Tumor response was evaluated using MRI according to RECIST. Survival was evaluated using Kaplan–Meier analysis. Results: A total of 110 patients (mean age 59.2 years) with 371 metastases received TACE (mean 5.4 sessions/patient, n = 110) with 76 (69%) receiving LITT (mean 1.6 session/patient) afterwards. TACE resulted in a mean decrease of mean maximum diameter of 52% ± 26.6 and volume change of −68.5% ± 22.9 in the 25 patients (23%) with partial response. Stable disease (n = 59, 54%). Progressive disease (n = 26, 23%). The RECIST outcome after LITT showed complete response (n = 13, 17%), partial response (n = 1, 1%), stable situation (n = 41, 54%) and progressive disease (n = 21, 28%). The mean time to progression (TTP) was 8.6 months. Median survival of all patients was 21.1 months. Conclusion: TACE with different protocols alone and in combination with LITT is a feasible palliative treatment option resulting in a median survival of 21.1 months for unresectable liver metastases of non-colorectal and non-breast cancer origin.

  3. Dietary aloe vera gel powder and extract inhibit azoxymethane- induced colorectal aberrant crypt foci in mice fed a high- fat diet.

    Science.gov (United States)

    Chihara, Takeshi; Shimpo, Kan; Kaneko, Takaaki; Beppu, Hidehiko; Higashiguchi, Takashi; Sonoda, Shigeru; Tanaka, Miyuki; Yamada, Muneo; Abe, Fumiaki

    2015-01-01

    Aloe vera gel exhibits protective effects against insulin resistance as well as lipid-lowering and anti-diabetic effects. The anti-diabetic compounds in this gel were identified as Aloe-sterols. Aloe vera gel extract (AVGE) containing Aloe-sterols has recently been produced using a new procedure. We previously reported that AVGE reduced large-sized intestinal polyps in Apc-deficient Min mice fed a high fat diet (HFD), suggesting that Aloe vera gel may protect against colorectal cancer. In the present study, we examined the effects of Aloe vera gel powder (AVGP) and AVGE on azoxymethane-induced colorectal preneoplastic aberrant crypt foci (ACF) in mice fed a HFD. Male C57BL/6J mice were given a normal diet (ND), HFD, HFD containing 0.5% carboxymethyl cellulose solution, which was used as a solvent for AVGE (HFDC), HFD containing 3% or 1% AVGP, and HFDC containing 0.0125% (H-) or 0.00375% (L-) AVGE. The number of ACF was significantly lower in mice given 3% AVGP and H-AVGE than in those given HFD or HFDC alone. Moreover, 3% AVGP, H-AVGE and L-AVGE significantly decreased the mean Ki-67 labeling index, assessed as a measure of cell proliferation in the colonic mucosa. In addition, hepatic phase II enzyme glutathione S-transferase mRNA levels were higher in the H-AVGE group than in the HFDC group. These results suggest that both AVGP and AVGE may have chemopreventive effects on colorectal carcinogenesis under the HFD condition. Furthermore, the concentration of Aloe-sterols was similar between 3% AVGP and H-AVGE, suggesting that Aloe-sterols were the main active ingredients in this experiment.

  4. Mulberry fruit prevents LPS-induced NF-κB/pERK/MAPK signals in macrophages and suppresses acute colitis and colorectal tumorigenesis in mice.

    Science.gov (United States)

    Qian, Zhengjiang; Wu, Zhiqin; Huang, Lian; Qiu, Huiling; Wang, Liyan; Li, Li; Yao, Lijun; Kang, Kang; Qu, Junle; Wu, Yonghou; Luo, Jun; Liu, Johnson J; Yang, Yi; Yang, Wancai; Gou, Deming

    2015-11-30

    Here, we investigated the impact of mulberry fruit (MBF) extracts on lipopolysaccharide (LPS)-induced inflammatory responses in RAW 264.7 macrophages, and the therapeutic efficacy of MBF diet in mice with dextran sulfate sodium (DSS)-induced acute colitis and MUC2(-/-) mice with colorectal cancer. In vitro, LPS-induced nitric oxide (NO) production was significantly inhibited by MBF extracts via suppressing the expression of proinflammatory molecules, including inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), interleukin-1 beta (IL-β) and IL-6. Particularly, a dose-dependent inhibition on LPS-induced inflammatory responses was observed following treatment with MBF dichloromethane extract (MBF-DE), in which linoleic acid and ethyl linolenate were identified as two active compounds. Moreover, we elucidated that MBF-DE attenuated LPS-induced inflammatory responses by blocking activation of both NF-κB/p65 and pERK/MAPK pathways. In vivo, DSS-induced acute colitis was significantly ameliorated in MBF-fed mice as gauged by weight loss, colon morphology and histological damage. In addition, MBF-fed MUC2(-/-) mice displayed significant decrease in intestinal tumor and inflammation incidence compared to control diet-fed group. Overall, our results demonstrated that MBF suppressed the development of intestinal inflammation and tumorgenesis both in vitro and in vivo, and supports the potential of MBF as a therapeutic functional food for testing in human clinical trials.

  5. Statins augment the chemosensitivity of colorectal cancer cells inducing epigenetic reprogramming and reducing colorectal cancer cell 'stemness' via the bone morphogenetic protein pathway

    NARCIS (Netherlands)

    Kodach, L.L.; Jacobs, R.J.; Voorneveld, P.W.; Wildenberg, M.E.; Verspaget, H.W.; van Wezel, T.; Morreau, H.; Hommes, D.W.; Peppelenbosch, M.P.; van den Brink, G.R.; Hardwick, J.C.H.

    2011-01-01

    Promoter hypermethylation is an important and potentially reversible mechanism of tumour suppressor gene silencing in cancer. Compounds that demethylate tumour suppressor genes and induce differentiation of cancer cells, but do not have toxic side effects, would represent an exciting option in cance

  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 percen

  7. 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 percen

  8. Inhibition of invasiveness and expression of epidermal growth factor receptor in human colorectal carcinoma cells induced by retinoic acid

    Institute of Scientific and Technical Information of China (English)

    SUNBAODONG; JINDANSONG

    1995-01-01

    Human amniotic basement membrane (HABM) model and agarose drop explant method were used to investigate the effects of retinoic acid(RA) on the invasive ness and adhesiveness to the basement membrane,and the migration of a highly invasive human colorectal cancer cell line CCL229.Results showed that 5×106 MRA markedly reduced the in vitro invasiveness and adhesiveness to the HABM,and the migration of the CCL229 cells.In addition,to elucidate the relation between expression of epidermal growth factor receptor(EGFR) and the invasiveness of the colorectal carcinoma cells,two well-differentiated,but with different invasiveness colorectal cancer cell lines were compared at mRNA level for expression of EGFR by using EGFR cDNA probe labeled with digoxigenin(DIG). Expression of EGFR was shown to be markedly higher in the highly invassive CCL229 cells than that in the low invasive CX-1 cells.Furthermore,expression of EGFR in RA treated CCL229 cells gradually decreased with time,the level being the lowest on day 6 of the RA treatment.

  9. Depletion of histone N-terminal-acetyltransferase Naa40 induces p53-independent apoptosis in colorectal cancer cells via the mitochondrial pathway.

    Science.gov (United States)

    Pavlou, Demetria; Kirmizis, Antonis

    2016-03-01

    Protein N-terminal acetylation is an abundant post-translational modification in eukaryotes implicated in various fundamental cellular and biochemical processes. This modification is catalysed by evolutionarily conserved N-terminal acetyltransferases (NATs) whose deregulation has been linked to cancer development and thus, are emerging as useful diagnostic and therapeutic targets. Naa40 is a highly selective NAT that acetylates the amino-termini of histones H4 and H2A and acts as a sensor of cell growth in yeast. In the present study, we examine the role of Naa40 in cancer cell survival. We demonstrate that depletion of Naa40 in HCT116 and HT-29 colorectal cancer cells decreases cell survival by enhancing apoptosis, whereas Naa40 reduction in non-cancerous mouse embryonic fibroblasts has no effect on cell viability. Specifically, Naa40 knockdown in colon cancer cells activates the mitochondrial caspase-9-mediated apoptotic cascade. Consistent with this, we show that caspase-9 activation is required for the induced apoptosis because treatment of cells with an irreversible caspase-9 inhibitor impedes apoptosis when Naa40 is depleted. Furthermore, the effect of Naa40-depletion on cell-death is mediated through a p53-independent mechanism since p53-null HCT116 cells still undergo apoptosis upon reduction of the acetyltransferase. Altogether, these findings reveal an anti-apoptotic role for Naa40 and exhibit its potential as a therapeutic target in colorectal cancers.

  10. Meiotic changes in Vicia faba L. subsequent to treatments of hydrazine hydrate and maleic hydrazide

    Directory of Open Access Journals (Sweden)

    Shaheen Husain

    2013-01-01

    Full Text Available Assessing the impact of mutagens for creating variations in crops like faba bean (Vicia faba L. is an important criterion in the contemporary world where food insecurity and malnutrition is alarming at the doors of various nations. Impact of two chemical mutagens viz. hydrazine hydrate (HZ and maleic hydrazide (MH on the two varieties (NDF-1 and HB-405 of Vicia faba were analysed in terms of meiotic behavior and pollen sterility. Since there are not enough data about the effect of these mutagens on the chromosomal behaviors of Vicia faba, this study presents the role of hydrazine hydrate and maleic hydrazide as well as various types of chromosomal aberrations in crop improvement. The lower concentration of mutagens showed less pollen sterility compared to the higher concentrations. Manipulation of plant structural component to induce desirable alternations provides valuable material for the breeders and could be used favorably for increasing mutation rate and obtaining a desirable spectrum of mutation in faba beans based on preliminary studies of cell division.

  11. Activity of the protector chlorophyllin or promoter of the genetic damage induced by the 1,2 dimethyl hydrazine; Actividad de la clorofilina protectora o promotora del dano genetico inducido por la 1,2 dimetil hidrazina

    Energy Technology Data Exchange (ETDEWEB)

    Guerrero M, M.G

    2004-07-01

    The chlorophyllin (CHLN) it is a porphyrin of soluble nutritious grade in water, derived of the chlorophyll that includes in their structure a copper atom. It has been reported that this pigment can act as anti mutagen, reducing the damage to the DNA caused by physical or chemical agents of direct or indirect action. Their anti carcinogen action has also been studied during the initiation phase induced for carcinogen as the aflatoxins and heterocyclic amines. In contrast the reports have increased on a probable promoter activity of the CHLN on the induced genetic damage. This effect was seen for the first time before the damage induced by alkylating agents in Salmonella. Recently it has been observed with the damage induced by gamma radiation, ENU and CrO{sub 3} in somatic cells of the wing of Drosophila and in the induction of tumors for 1,2-dimethylhydrazine (DMH) in mice. Presently study is evaluated the protective effect or promoter of the CHLN before the genetic damage induced by 1,2-dimethylhydrazine, by means of the bioassay mutation and somatic recombination (SMART) in the wing of Drosophila melanogaster. Its were pretreated with CHLN or SAC to transheterocygotes larvas for two locus of the chromosome three mwh+/+flr{sup 3}; later on they are retarded the chronic treatment with DMH 0, 1, 2 and 3 days. It was measured the toxicity and the speed of development of the treated individuals. The wings of those adults that emerged were analyzed to register the number and the size of stains. The results indicated: differences in the viability of the individuals of the groups SAC + DMH vs CHLN + DMH only in the treated immediately after the pretreatment (DRT-0) that the CHLN doesn't modify the rate of the treated individuals development. The results of somatic mutation indicated that the CHLN has a protective effect only immediately after the pretreatment (DRT-0) however in DRT-1, 2 and 3 showed a promoter effect of genetic damage. (Author)

  12. Colorectal cancer screening.

    Science.gov (United States)

    Burt, Randall W; Cannon, Jamie A; David, Donald S; Early, Dayna S; Ford, James M; Giardiello, Francis M; Halverson, Amy L; Hamilton, Stanley R; Hampel, Heather; Ismail, Mohammad K; Jasperson, Kory; Klapman, Jason B; Lazenby, Audrey J; Lynch, Patrick M; Mayer, Robert J; Ness, Reid M; Provenzale, Dawn; Rao, M Sambasiva; Shike, Moshe; Steinbach, Gideon; Terdiman, Jonathan P; Weinberg, David; Dwyer, Mary; Freedman-Cass, Deborah

    2013-12-01

    Mortality from colorectal cancer can be reduced by early diagnosis and by cancer prevention through polypectomy. These NCCN Guidelines for Colorectal Cancer Screening describe various colorectal screening modalities and recommended screening schedules for patients at average or increased risk of developing colorectal cancer. In addition, the guidelines provide recommendations for the management of patients with high-risk colorectal cancer syndromes, including Lynch syndrome. Screening approaches for Lynch syndrome are also described.

  13. Anti-mutagenic lichen extract has double-edged effect on azoxymethane-induced colorectal oncogenesis in C57BL/6J mice.

    Science.gov (United States)

    He, Xiaoqiong; Hu, Ying; Winter, Jean; Young, Graeme P

    2010-01-01

    This study compared the effects of three anti-mutagenic lichen extracts on colorectal oncogenesis in azoxymethane (AOM)-treated mice and determined whether the extracts also regulated the homeostatic response to genotoxic damage. C57BL/6J mice (n = 12 per group) were treated with the lichen extracts Antimutagen-He (AMH): AMH-C, AMH-D, or AMH-E dimethyl sulfoxide (DMSO, control) for 2 weeks. At the end of the treatment, mice were given a single AOM injection to induce DNA damage and killed 6 h later for measuring apoptosis and proliferation. Apoptotic and proliferation indexes in mice treated with AMH-C, AMH-D, and AMH-E were 0.61%, 1.41%, and 0.77%; and 30.62%, 21.93%, and 27.27%, respectively, which were significantly lower than those of control mice (5.88% and 38.69%) (p lichen extracts on colorectal cancer, separate groups of mice (n = 25 per group) treated with AMH-C, AMH-D, AMH-E, or DMSO were given 4-weekly AOM injections to induce oncogenesis. Mice were killed 24 weeks after the last AOM injection for assessing colon tumor formation. Colonic tumor incidences were 47.3%, 13%, and 20%; the tumor volumes were 18.47, 2.75, and 10.78 mm(3), respectively, in mice treated with AMH-C (p 0.05), compared to 24% and 13.28 mm(3) in mice of control correspondingly. No lichen extract showed evident toxic effects on mice. No usnic acid was found in these lichen extracts. The regulation of acute apoptosis and cell proliferation in colonic epithelial cells and the anti-mutagenesis do not seem directly related to the cancer protective effect.

  14. Influences of the interferon induced transmembrane protein I on the proliferation, invasion, and metastasis of the colorectal cancer SW480 cell lines

    Institute of Scientific and Technical Information of China (English)

    HE Jing-dong; LUO Hong-lei; LI Jin; FENG Wan-ting; CHEN Long-bang

    2012-01-01

    Background Interferon-induced transmembrane protein 1 (IFITM1) has been identified as a molecular marker of the colorectal tumors; however its influences on the biological behaviors of the colorectal cancer cells are currently unknown.We aimed to study the influences of IFITM1 on the proliferation,invasion,and metastasis of the colorectal cancer SW480 cell lines.Methods We constructed IFITM1/pEGFP-C3 recombinant plasmids and transfected them into the colorectal cancer SW480 cell lines.IFITM1/pEGFP-C3 recombinant plasmids were identified by means of immunofluorescence,laser confocal scanning microscopy,and reverse transcription polymerase chain reaction.IFITM1/SW480 cells with stable over-expression of IFITM1 were confirmed by G418 screening.The influences of IFITM1 on the proliferation of the SW480 cell lines were investigated by MTT assay and tumor transplantation experiments in nude mice.Cell invasion experiments were performed to determine the invasion capacity of the IFITM1/SW480 cells.Matrix metalloproteinase 2 (MMP-2) and MMP-9 activities were detected by the gelatin zymographic analysis,and MMP-9 expression by the Western blotting analysis.Results IFITM1/pEGFP-C3 recombinant plasmids were successfully constructed in this study,and the IFITM1/SW480 cells with stable IFITM1 gene over-expression were confirmed by G418 screening.MTT results showed that the proliferation of the IFITM1/SW480 cells was significantly enhanced (P <0.01).Tumors were harvested from four weeks old mice.Tumor volumes were (1347.00±60.94) mm3,(1032.40±111.38) mm3 and (1018.78±28.83) mm3; and tumor weights were (1522.34±62.76) mg,(1137.78±97.22) mg and (1155.76±133.31) mg for mice inoculated with the IFITM1/SW480 cells,pEGFP-C3/SW480 cells and SW480 cells,respectively.Tumor volumes and weights from mice inoculated with the IFITM1/SW480 cells were significantly increased (P <0.01).In addition,the numbers of the SW480 cells and IFITM1/SW480 cells that migrated through Matrigel were

  15. Epithelial-mesenchymal transition (EMT) induced by TNF-α requires AKT/GSK-3β-mediated stabilization of snail in colorectal cancer.

    Science.gov (United States)

    Wang, Hao; Wang, Hong-Sheng; Zhou, Bin-Hua; Li, Cui-Lin; Zhang, Fan; Wang, Xian-Feng; Zhang, Ge; Bu, Xian-Zhang; Cai, Shao-Hui; Du, Jun

    2013-01-01

    Chronic inflammation-promoted metastasis has been considered as a major challenge in cancer therapy. Pro-inflammatory cytokine TNFα can induce cancer invasion and metastasis associated with epithelial-mesenchymal transition (EMT). However, the underlying mechanisms are not entirely clear. In this study, we showed that TNFα induces EMT in human HCT116 cells and thereby promotes colorectal cancer (CRC) invasion and metastasis. TNFα-induced EMT was characterized by acquiring mesenchymal spindle-like morphology and increasing the expression of N-cadherin and fibronectin with a concomitant decrease of E-cadherin and Zona occludin-1(ZO-1). TNFα treatment also increased the expression of transcription factor Snail, but not Slug, ZEB1 and Twist. Overexpression of Snail induced a switch from E-cadherin to N-cadherin expression in HCT116 cells, which is a characteristic of EMT. Conversely, knockdown of Snail significantly attenuated TNFα-induced EMT in HCT116 cells, suggesting that Snail plays a crucial role in TNFα-induced EMT. Interestingly, exposure to TNFα rapidly increased Snail protein expression and Snail nuclear localization but not mRNA level upregulation. Finally, we demonstrated that TNFα elevated Snail stability by activating AKT pathway and subsequently repressing GSK-3β activity and decreasing the association of Snail with GSK-3β. Knockdown of GSK-3β further verified our finding. Taken together, these results revealed that AKT/GSK-3β-mediated stabilization of Snail is required for TNFα-induced EMT in CRC cells. Our study provides a better understanding of inflammation-induced CRC metastasis.

  16. Epithelial–Mesenchymal Transition (EMT) Induced by TNF-α Requires AKT/GSK-3β-Mediated Stabilization of Snail in Colorectal Cancer

    Science.gov (United States)

    Wang, Hao; Wang, Hong-Sheng; Zhou, Bin-Hua; Li, Cui-Lin; Zhang, Fan; Wang, Xian-Feng; Zhang, Ge; Bu, Xian-Zhang; Cai, Shao-Hui; Du, Jun

    2013-01-01

    Chronic inflammation-promoted metastasis has been considered as a major challenge in cancer therapy. Pro-inflammatory cytokine TNFα can induce cancer invasion and metastasis associated with epithelial–mesenchymal transition (EMT). However, the underlying mechanisms are not entirely clear. In this study, we showed that TNFα induces EMT in human HCT116 cells and thereby promotes colorectal cancer (CRC) invasion and metastasis. TNFα-induced EMT was characterized by acquiring mesenchymal spindle-like morphology and increasing the expression of N-cadherin and fibronectin with a concomitant decrease of E-cadherin and Zona occludin-1(ZO-1). TNFα treatment also increased the expression of transcription factor Snail, but not Slug, ZEB1 and Twist. Overexpression of Snail induced a switch from E-cadherin to N-cadherin expression in HCT116 cells, which is a characteristic of EMT. Conversely, knockdown of Snail significantly attenuated TNFα-induced EMT in HCT116 cells, suggesting that Snail plays a crucial role in TNFα-induced EMT. Interestingly, exposure to TNFα rapidly increased Snail protein expression and Snail nuclear localization but not mRNA level upregulation. Finally, we demonstrated that TNFα elevated Snail stability by activating AKT pathway and subsequently repressing GSK-3β activity and decreasing the association of Snail with GSK-3β. Knockdown of GSK-3β further verified our finding. Taken together, these results revealed that AKT/GSK-3β-mediated stabilization of Snail is required for TNFα-induced EMT in CRC cells. Our study provides a better understanding of inflammation-induced CRC metastasis. PMID:23431386

  17. Get Tested for Colorectal Cancer

    Science.gov (United States)

    ... Print This Topic En español Get Tested for Colorectal Cancer Browse Sections The Basics Overview What to Expect ... section Overview 2 of 6 sections The Basics: Colorectal Cancer What is colorectal cancer? Colorectal cancer is a ...

  18. Ethanol enhances arsenic-induced cyclooxygenase-2 expression via both NFAT and NF-κB signalings in colorectal cancer cells.

    Science.gov (United States)

    Wang, Lei; Hitron, John Andrew; Wise, James T F; Son, Young-Ok; Roy, Ram Vinod; Kim, Donghern; Dai, Jin; Pratheeshkumar, Poyil; Zhang, Zhuo; Xu, Mei; Luo, Jia; Shi, Xianglin

    2015-10-15

    Arsenic is a known carcinogen to humans, and chronic exposure to environmental arsenic is a worldwide health concern. As a dietary factor, ethanol carries a well-established risk for malignancies, but the effects of co-exposure to arsenic and ethanol on tumor development are not well understood. In the present study, we hypothesized that ethanol would enhance the function of an environmental carcinogen such as arsenic through increase in COX-2 expression. Our in vitro results show that ethanol enhanced arsenic-induced COX-2 expression. We also show that the increased COX-2 expression associates with intracellular ROS generation, up-regulated AKT signaling, with activation of both NFAT and NF-κB pathways. We demonstrate that antioxidant enzymes have an inhibitory effect on arsenic/ethanol-induced COX-2 expression, indicating that the responsive signaling pathways from co-exposure to arsenic and ethanol relate to ROS generation. In vivo results also show that co-exposure to arsenic and ethanol increased COX-2 expression in mice. We conclude that ethanol enhances arsenic-induced COX-2 expression in colorectal cancer cells via both the NFAT and NF-κB pathways. These results imply that, as a common dietary factor, ethanol ingestion may be a compounding risk factor for arsenic-induced carcinogenesis/cancer development.

  19. Synthesis and in vitro anti-proliferative activity of some novel isatins conjugated with quinazoline/phthalazine hydrazines against triple-negative breast cancer MDA-MB-231 cells as apoptosis-inducing agents.

    Science.gov (United States)

    Eldehna, Wagdy M; Almahli, Hadia; Al-Ansary, Ghada H; Ghabbour, Hazem A; Aly, Mohamed H; Ismael, Omnia E; Al-Dhfyan, Abdullah; Abdel-Aziz, Hatem A

    2017-12-01

    Treatment of patients with triple-negative breast cancer (TNBC) is challenging due to the absence of well- defined molecular targets and the heterogeneity of such disease. In our endeavor to develop potent isatin-based anti-proliferative agents, we utilized the hybrid-pharmacophore approach to synthesize three series of novel isatin-based hybrids 5a-h, 10a-h and 13a-c, with the prime goal of developing potent anti-proliferative agents toward TNBC MDA-MB-231 cell line. In particular, compounds 5e and 10g were the most active hybrids against MDA-MB-231 cells (IC50 = 12.35 ± 0.12 and 12.00 ± 0.13 μM), with 2.37- and 2.44-fold increased activity than 5-fluorouracil (5-FU) (IC50 = 29.38 ± 1.24 μM). Compounds 5e and 10g induced the intrinsic apoptotic mitochondrial pathway in MDA-MB-231; evidenced by the reduced expression of the anti-apoptotic protein Bcl-2, the enhanced expression of the pro-apoptotic protein Bax and the up-regulated active caspase-9 and caspase-3 levels. Furthermore, 10g showed significant increase in the percent of annexin V-FITC positive apoptotic cells from 3.88 to 31.21% (8.4 folds compared to control).

  20. Developing a New Sampling And Analysis Method For Hydrazine And Monomethyl Hydrazine: Using a Derivatizing Agent With Solid Phase Microextraction

    Science.gov (United States)

    Allen, John

    2001-01-01

    Solid phase microextraction (SPME) will be used to develop a method for detecting monomethyl hydrazine (MMH) and hydrazine (Hz). A derivatizing agent, pentafluorobenzoyl chloride (PFBCI), is known to react readily with MMH and Hz. The SPME fiber can either be coated with PFBCl and introduced into a gaseous stream containing MMH, or PFBCl and MMH can react first in a syringe barrel and after a short equilibration period a SPME is used to sample the resulting solution. These methods were optimized and compared. Because Hz and MMH can degrade the SPME, letting the reaction occur first gave better results. Only MMH could be detected using either of these methods. Future research will concentrate on constructing calibration curves and determining the detection limit.

  1. Developing a New Sampling And Analysis Method For Hydrazine And Monomethyl Hydrazine: Using a Derivatizing Agent With Solid Phase Microextraction

    Science.gov (United States)

    Allen, John

    2001-01-01

    Solid phase microextraction (SPME) will be used to develop a method for detecting monomethyl hydrazine (MMH) and hydrazine (Hz). A derivatizing agent, pentafluorobenzoyl chloride (PFBCI), is known to react readily with MMH and Hz. The SPME fiber can either be coated with PFBCl and introduced into a gaseous stream containing MMH, or PFBCl and MMH can react first in a syringe barrel and after a short equilibration period a SPME is used to sample the resulting solution. These methods were optimized and compared. Because Hz and MMH can degrade the SPME, letting the reaction occur first gave better results. Only MMH could be detected using either of these methods. Future research will concentrate on constructing calibration curves and determining the detection limit.

  2. Monomethylhydrazine versus hydrazine fuels - Test results using a 100 pound thrust bipropellant rocket engine

    Science.gov (United States)

    Smith, J. A.; Stechman, R. C.

    1981-01-01

    A test program was performed to evaluate hydrazine (N2H4) as a fuel for a 445 Newton (100 lbf) thrust bipropellant rocket engine. Results of testing with an identical thruster utilizing monomethylhydrazine (MMH) are included for comparison. Engine performance with hydrazine fuel was essentially identical to that experienced with monomethylhydrazine although higher combustor wall temperatures (approximately 400 F) were obtained with hydrazine. Results are presented which indicate that hydrazine as a fuel is compatible with Marquardt bipropellant rocket engines which use monomethylhydrazine as a baseline fuel.

  3. Evaluation of hydrazine reduction by cellulose acetate filters using infrared tunable diode laser spectroscopy.

    Science.gov (United States)

    Harward, Charles N; Parrish, Milton E; Plunkett, Susan E; Banyasz, Joseph L; Shafer, Kenneth H

    2002-11-15

    Cellulose acetate (CA) filters have been investigated to determine their hydrazine (N2H4) breakthrough characteristics using a system based on tunable diode laser absorption spectroscopy (TDIAS). The breakthrough mass loading sorption curves for hydrazine were dependent on both the flow rate and the concentration. In experiments using a 4.5 ppmv hydrazine standard, the amounts of hydrazine retained by the CA filter were 4.25 microg at a flow rate of 2.82 L/min and 65 microg at a flow rate of 0.28 L/min. These loadings are much greater than the 31.5 ng/cigarette of hydrazine reported in smoke for unfiltered cigarettes. Further, CA filters exposed to four and eight puffs of smoke actually made the filter more efficient in retaining hydrazine compared to CA filters that had not been exposed to smoke. Therefore, if hydrazine is present in smoke at the levels reported in unfiltered cigarettes, all of the hydrazine would be trapped by the CA filter, and would be unable to break through during smoking. A unique feature of this analytical method is that the instrument does not require calibration after molecular parameters have been determined, in this case from previously acquired quantitative hydrazine FT-IR reference spectra.

  4. Fabrication of liquid crystal based sensor for detection of hydrazine vapours

    Science.gov (United States)

    Nandi, Rajib; Singh, Sachin Kumar; Singh, Hemant Kumar; Singh, Bachcha; Singh, Ranjan K.

    2014-10-01

    A novel liquid crystal (LC) based sensor to detect trace level amount of hydrazine vapour has been developed. The LC 4‧-pentyl-4-biphenylcarbonitrile (5CB) doped with 0.5 wt% 4-decyloxy benzaldehyde (DBA) shows dark to bright optical texture upon exposure of hydrazine vapours as revealed by polarizing optical microscopy under crossed polarizers. The hydrazine interacts with the doped DBA and form diimine compound which disrupt the orientation of aligned 5CB. The interaction between DBA and hydrazine has been also studied by Raman spectroscopy.

  5. Combined olaparib and oxaliplatin inhibits tumor proliferation and induces G2/M arrest and γ-H2AX foci formation in colorectal cancer

    Directory of Open Access Journals (Sweden)

    Xu K

    2015-10-01

    Full Text Available Kaiwu Xu,1* Zhihui Chen,2* Yi Cui,1 Changjiang Qin,2 Yulong He,2 Xinming Song2 1Endoscopy Center, 2Gastrointestinal Surgery Center, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong Province, People’s Republic of China *These authors contributed equally to this work Background: Poly (ADP-ribose polymerase 1 (PARP1 has an important role in homologous recombination repair. The purpose of this study was to investigate the effect of PARP1 inhibitor on oxaliplatin treatment for colorectal cancer (CRC. Methods: A cell counting kit-8 assay was used to determine the sensitivity of CRC cells to olaparib and/or oxaliplatin. The gene and protein expressions of PARP1 and the gamma histone variant H2AX (γH2AX were measured by real-time quantitative polymerase chain reaction and western blotting, respectively. The γH2AX foci formation assay was used to investigate the influence of treatments on cells. Flow cytometry was used to examine the changes in cell cycle distribution. Finally, we investigated the combination of olaparib and oxaliplatin in the CRC tumor model. Results: Olaparib changed the expression of γH2AX and PARP1, and increased the sensitivity of CRC cells to oxaliplatin. The γH2AX foci assay showed that olaparib did not induce double-strand breaks (DSBs alone, but it enhanced the induction of DSBs by oxaliplatin. The flow cytometry results showed that cells exposed to combination treatment had more G2/M-phase cells than control. Additionally, tumor xenograft studies suggested that combined treatment inhibited the growth of CRC. Conclusion: CRC cells are sensitized to combined treatment with olaparib and oxaliplatin, and this could be a promising strategy for clinical chemotherapy in CRC. Keywords: olaparib, oxaliplatin, chemosensitization, colorectal cancer

  6. Assessment of Local Control after Laser-Induced Thermotherapy of Liver Metastases from Colorectal Cancer: Contribution of FDG-PET in Patients with Clinical Suspicion of Progressive Disease

    Energy Technology Data Exchange (ETDEWEB)

    Denecke, T.; Steffen, I.; Hildebrandt, B.; Ruehl, R.; Streitparth, F.; Lehmk uhl, L.; Langrehr, J.; Ricke, J.; Amthauer, H.; Lopez Haenninen, E. [Klinik fuer Strahlenheilkunde, Bereiche Radiologie und Nuklearmedizin, Medizinische Klinik mit Schwerpunkt Haematologie Onkologie, and Klinik fuer Allgemein-, Viszeral-, und T ransplantationschirurgie, Campus Virchow-Klinikum, Charite - Universitaetsmedizi n Berlin, (Germany)

    2007-10-15

    Background: Management of patients after locally ablative treatment of liver metastases requires exact information about local control and systemic disease status. To fulfill these requirements, whole-body imaging using positron emission tomography with {sup 18}F-fluorodeoxyglucose (FDG-PET) is a promising alternative to morphologic imaging modalities such as computed tomography (CT) and magnetic resonance imaging (MRI). Purpose: To evaluate FDG-PET for the assessment of local control and systemic disease in patients with clinical suspicion of tumor progression after laser-induced thermotherapy (LITT) of colorectal liver metastases. Material and Methods: In 21 patients with suspicion of progressive disease after LITT, whole-body FDG-PET was performed. The presence of viable tumor within treated lesions, new liver metastases, and extrahepatic disease was evaluated visually and semi quantitatively (maximal standard uptake value [SUVmax], tumor-to-normal ratio [T/N]). The standard of reference was histopathology (n = 25 lesions) and/or clinical follow-up (>12 months) including contrast-enhanced MRI of the liver. Results: Among 54 metastases treated with LITT, 29 had residual tumor. Receiver operating characteristic (ROC) analysis of SUVmax (area under the curve (AUC) 0.990) and T/N (AUC 0.968) showed a significant discrimination level of negative or positive lesion status with an equal accuracy of 94% (51/54). The overall accuracy of visual FDG-PET was 96% (52/54), with one false-negative lesion among six examined within 3 days after LITT, and one false-positive lesion examined 54 days after LITT. In the detection of new intra- and extrahepatic lesions, FDG-PET resulted in correct alteration of treatment strategy in 43% of patients (P = 0.007). Conclusion: FDG-PET is a promising tool for the assessment of local control and whole-body restaging in patients with clinical suspicion of tumor progression after locally ablative treatment of colorectal liver metastases with

  7. Loss of Sirt1 function improves intestinal anti-bacterial defense and protects from colitis-induced colorectal cancer.

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    Giuseppe Lo Sasso

    Full Text Available Dysfunction of Paneth and goblet cells in the intestine contributes to inflammatory bowel disease (IBD and colitis-associated colorectal cancer (CAC. Here, we report a role for the NAD+-dependent histone deacetylase SIRT1 in the control of anti-bacterial defense. Mice with an intestinal specific Sirt1 deficiency (Sirt1int-/- have more Paneth and goblet cells with a consequent rearrangement of the gut microbiota. From a mechanistic point of view, the effects on mouse intestinal cell maturation are mediated by SIRT1-dependent changes in the acetylation status of SPDEF, a master regulator of Paneth and goblet cells. Our results suggest that targeting SIRT1 may be of interest in the management of IBD and CAC.

  8. Inhibition of fried meat-induced colorectal DNA damage and altered systemic genotoxicity in humans by crucifera, chlorophyllin, and yogurt.

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    Daniel T Shaughnessy

    Full Text Available Dietary exposures implicated as reducing or causing risk for colorectal cancer may reduce or cause DNA damage in colon tissue; however, no one has assessed this hypothesis directly in humans. Thus, we enrolled 16 healthy volunteers in a 4-week controlled feeding study where 8 subjects were randomly assigned to dietary regimens containing meat cooked at either low (100°C or high temperature (250°C, each for 2 weeks in a crossover design. The other 8 subjects were randomly assigned to dietary regimens containing the high-temperature meat diet alone or in combination with 3 putative mutagen inhibitors: cruciferous vegetables, yogurt, and chlorophyllin tablets, also in a crossover design. Subjects were nonsmokers, at least 18 years old, and not currently taking prescription drugs or antibiotics. We used the Salmonella assay to analyze the meat, urine, and feces for mutagenicity, and the comet assay to analyze rectal biopsies and peripheral blood lymphocytes for DNA damage. Low-temperature meat had undetectable levels of heterocyclic amines (HCAs and was not mutagenic, whereas high-temperature meat had high HCA levels and was highly mutagenic. The high-temperature meat diet increased the mutagenicity of hydrolyzed urine and feces compared to the low-temperature meat diet. The mutagenicity of hydrolyzed urine was increased nearly twofold by the inhibitor diet, indicating that the inhibitors enhanced conjugation. Inhibitors decreased significantly the mutagenicity of un-hydrolyzed and hydrolyzed feces. The diets did not alter the levels of DNA damage in non-target white blood cells, but the inhibitor diet decreased nearly twofold the DNA damage in target colorectal cells. To our knowledge, this is the first demonstration that dietary factors can reduce DNA damage in the target tissue of fried-meat associated carcinogenesis.ClinicalTrials.gov NCT00340743.

  9. Tests for the mutagenic action of a number of chemicals on Haemophilus influenzae with special emphasis on hydrazine

    Energy Technology Data Exchange (ETDEWEB)

    Kimball, R.F.; Hirsch, B.F.

    1975-01-01

    A number of chemicals have been tested for their ability to produce novobiocin-resistant mutants in Haemophilus influenzae. Of these, hydrazine (HZ) proved unique because it induced a fairly high incidence of mutation without killing significant numbers of cells at concentrations ranging over nearly four orders of magnitude. Moreover, its dose--effect curve increased very slowly initially and reached a relatively low maximum. It is suggested that HZ may be acting as both a mutagen and an antimutagen in this system. (auth)

  10. Phorbol myristate acetate and Bryostatin 1 rescue IFN-gamma inducibility of MHC class II molecules in LS1034 colorectal carcinoma cell line

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    Wiseman Charles L

    2003-03-01

    Full Text Available Abstract Background The expression of major histocompatibility complex class II (MHCII antigens in both mouse and human tumors is rare, and these antigens are not easily inducible by IFN-gamma (IFNg. Since MHCII may play an important role in the development of host antitumor immune response, we explored the possibility of restoring MHCII inducibility in several IFNg-resistant tumor cell lines using protein kinase C (PKC agonists phorbol myristate acetate (PMA or Bryostatin. Results Tumor cells were co-cultured with various concentrations of PMA and IFNg for 48 hr. The expression of MHCII antigens and receptors IFNgR1 and IFNgR2 was determined by flow cytometry. We showed that the presence of as little as 0.1 ng/ml of PMA in tissue culture restored the ability of weakly inducible LS1034 colon carcinoma cells to express MHCII in response to IFNg (100 – 10,000 IU/ml in a dose-dependent manner. Likewise, Bryostatin 1, as low as 10 ng/ml produced a 5–6 fold upregulation of MHCII. The effect of PMA was not observed in two other poorly responding cell lines, MSTO-211H mesothelioma and HepG2 hepatocellular carcinoma, and was abrogated by relatively high concentrations of PKC inhibitors staurosporine (100 nM and GF 109203X (1,000 nM. Both surface and intracellular staining of all cell lines with antibodies against IFNgR1 and IFNgR2 failed to detect any increase in IFNg receptor expression following incubation with PMA. Conclusion In this study we showed that IFNg-inducibility of MHCII antigens in weakly inducible LS1034 colorectal carcinoma cell line can be rescued by concomitant incubation with PKC agonists. Bryostatin 1 may be considered for further investigation of IFNg-dependent MHCII induction in resistant tumors in vivo.

  11. Phorbol myristate acetate and Bryostatin 1 rescue IFN-gamma inducibility of MHC class II molecules in LS1034 colorectal carcinoma cell line

    Science.gov (United States)

    Kudinov, Yuri; Wiseman, Charles L; Kharazi, Alexander I

    2003-01-01

    Background The expression of major histocompatibility complex class II (MHCII) antigens in both mouse and human tumors is rare, and these antigens are not easily inducible by IFN-gamma (IFNg). Since MHCII may play an important role in the development of host antitumor immune response, we explored the possibility of restoring MHCII inducibility in several IFNg-resistant tumor cell lines using protein kinase C (PKC) agonists phorbol myristate acetate (PMA) or Bryostatin. Results Tumor cells were co-cultured with various concentrations of PMA and IFNg for 48 hr. The expression of MHCII antigens and receptors IFNgR1 and IFNgR2 was determined by flow cytometry. We showed that the presence of as little as 0.1 ng/ml of PMA in tissue culture restored the ability of weakly inducible LS1034 colon carcinoma cells to express MHCII in response to IFNg (100 – 10,000 IU/ml) in a dose-dependent manner. Likewise, Bryostatin 1, as low as 10 ng/ml produced a 5–6 fold upregulation of MHCII. The effect of PMA was not observed in two other poorly responding cell lines, MSTO-211H mesothelioma and HepG2 hepatocellular carcinoma, and was abrogated by relatively high concentrations of PKC inhibitors staurosporine (100 nM) and GF 109203X (1,000 nM). Both surface and intracellular staining of all cell lines with antibodies against IFNgR1 and IFNgR2 failed to detect any increase in IFNg receptor expression following incubation with PMA. Conclusion In this study we showed that IFNg-inducibility of MHCII antigens in weakly inducible LS1034 colorectal carcinoma cell line can be rescued by concomitant incubation with PKC agonists. Bryostatin 1 may be considered for further investigation of IFNg-dependent MHCII induction in resistant tumors in vivo. PMID:12787470

  12. Lactobacillus farciminis treatment attenuates stress-induced overexpression of Fos protein in spinal and supraspinal sites after colorectal distension in rats.

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    Ait-Belgnaoui, A; Eutamene, H; Houdeau, E; Bueno, L; Fioramonti, J; Theodorou, V

    2009-05-01

    Abstract Irritable bowel syndrome (IBS), frequently associated with psychological distress, is characterized by hypersensitivity to gut wall distension. Some probiotics are able to alleviate IBS symptoms and reduce visceromotor response to mechanical stimuli in animals. Moreover, we have previously shown that Lactobacillus farciminis treatment abolished the hyperalgesia to colorectal distension (CRD) induced by acute stress. The aims of the present study were to determine whether (i) stress-induced visceral hyperalgesia modifies the expression of Fos, a marker of general neuronal activation, induced by CRD, (ii) this activation can be modulated by L. farciminis treatment. Female rats were treated by L. farciminis and CRD was performed after partial restraint stress (PRS) or sham-PRS. The expression of Fos protein was measured by immunohistochemistry. After CRD or PRS, Fos expression was increased in spinal cord section (S1), nucleus tractus solitarius (NTS), paraventricular nucleus (PVN) of the hypothalamus, and in the medial nucleus of the amygdala (MeA). The combination of both stimuli, PRS and CRD, markedly increased this Fos overexpression in the sacral spinal cord section, PVN and MeA, but not in NTS. By contrast, a pretreatment with L. farciminis significantly reduced the number of Fos positive cells in these area. This study shows that PRS enhances Fos protein expression induced by CRD at the spinal and supraspinal levels in rats. Lactobacillus farciminis treatment inhibited this enhancing effect, suggesting that the antinociceptive effect of this probiotic strain results from a decrease of the stress-induced activation/sensitization of sensory neurons at the spinal and supraspinal level.

  13. Colorectal Cancer Prevention

    Science.gov (United States)

    ... alcoholic beverages per day increases the risk of colorectal cancer. Drinking alcohol is also linked to the risk of forming large colorectal adenomas (benign tumors). Cigarette smoking Cigarette smoking is ...

  14. Quercetin induces cell cycle arrest and apoptosis in CD133(+) cancer stem cells of human colorectal HT29 cancer cell line and enhances anticancer effects of doxorubicin.

    Science.gov (United States)

    Atashpour, Shekoufeh; Fouladdel, Shamileh; Movahhed, Tahereh Komeili; Barzegar, Elmira; Ghahremani, Mohammad Hossein; Ostad, Seyed Nasser; Azizi, Ebrahim

    2015-07-01

    The colorectal cancer stem cells (CSCs) with the CD133(+) phenotype are a rare fraction of cancer cells with the ability of self-renewal, unlimited proliferation and resistance to treatment. Quercetin has anticancer effects with the advantage of exhibiting low side effects. Therefore, we evaluated the anticancer effects of quercetin and doxorubicin (Dox) in HT29 cancer cells and its isolated CD133(+) CSCs. The CSCs from HT29 cells were isolated using CD133 antibody conjugated to magnetic beads by MACS. Anticancer effects of quercetin and Dox alone and in combination on HT29 cells and CSCs were evaluated using MTT cytotoxicity assay and flow cytometry analysis of cell cycle distribution and apoptosis induction. The CD133(+) CSCs comprised about 10% of HT29 cells. Quercetin and Dox alone and in combination inhibited cell proliferation and induced apoptosis in HT29 cells and to a lesser extent in CSCs. Quercetin enhanced cytotoxicity and apoptosis induction of Dox at low concentration in both cell populations. Quercetin and Dox and their combination induced G2/M arrest in the HT29 cells and to a lesser extent in CSCs. The CSCs were a minor population with a significantly high level of drug resistance within the HT29 cancer cells. Quercetin alone exhibited significant cytotoxic effects on HT29 cells and also increased cytoxicity of Dox in combination therapy. Altogether, our data showed that adding quercetin to Dox chemotherapy is an effective strategy for treatment of both CSCs and bulk tumor cells.

  15. Overexpression of snail induces epithelial-mesenchymal transition and a cancer stem cell-like phenotype in human colorectal cancer cells.

    Science.gov (United States)

    Fan, Fan; Samuel, Shaija; Evans, Kurt W; Lu, Jia; Xia, Ling; Zhou, Yunfei; Sceusi, Eric; Tozzi, Federico; Ye, Xiang-Cang; Mani, Sendurai A; Ellis, Lee M

    2012-08-01

    Epithelial-mesenchymal transition (EMT) is a critical process providing tumor cells with the ability to migrate and escape from the primary tumor and metastasize to distant sites. Recently, EMT was shown to be associated with the cancer stem cell (CSC) phenotype in breast cancer. Snail is a transcription factor that mediates EMT in a number of tumor types, including colorectal cancer (CRC). Our study was done to determine the role of Snail in mediating EMT and CSC function in CRC. Human CRC specimens were stained for Snail expression, and human CRC cell lines were transduced with a retroviral Snail construct or vector control. Cell proliferation and chemosensitivity to oxaliplatin of the infected cells were determined by the MTT (colorimetric 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. Migration and invasion were determined in vitro using modified Boyden chamber assays. EMT and putative CSC markers were analyzed using Western blotting. Intravenous injection of tumor cells was done to evaluate their metastatic potential in mice. Snail was overexpressed in human CRC surgical specimens. This overexpression induced EMT and a CSC-like phenotype in human CRC cells and enhanced cell migration and invasion (P Snail overexpression also led to an increase in metastasis formation in vivo (P Snail-overexpressing CRC cells were more chemoresistant to oxaliplatin than control cells. Increased Snail expression induces EMT and the CSC-like phenotype in CRC cells, which enhance cancer cell invasion and chemoresistance. Thus, Snail is a potential therapeutic target in metastatic CRC.

  16. Retrospective Comparative Study of the Effects of Dendritic Cell Vaccine and Cytokine-Induced Killer Cell Immunotherapy with that of Chemotherapy Alone and in Combination for Colorectal Cancer

    Directory of Open Access Journals (Sweden)

    Jingxiu Niu

    2014-01-01

    Full Text Available Purpose. This retrospective study determined the delayed-type hypersensitivity (DTH skin test and safety of dendritic cell (DC vaccine and cytokine-induced killer (CIK cell immunotherapy and the survival compared to chemotherapy in 239 colorectal cancer (CRC patients. Methods. DTH and safety of the immunotherapy were recorded. The overall survival (OS and disease free survival curves were compared according to the immunotherapy and/or chemotherapy received with Kaplan-Meier estimates. Results. Of the 70 patients who received immunotherapy, 62.86% had a positive DTH skin test, 38.57% developed fever, 47.14% developed insomnia, 38.57% developed anorexia, 4.29% developed joint soreness, and 11.43% developed skin rash. For 204 resectable CRC patients, median survival time (MST (198.00 days was significantly longer in patients with immunotherapy plus chemotherapy than with chemotherapy alone (106.00 days (P=0.02. For 35 patients with unresectable or postsurgery relapsed CRC and who were confirmed to be dead, no statistical difference was observed in the MST between the patients treated with immunotherapy and with chemotherapy (P=0.41. MST in the patients treated with chemotherapy plus immunotherapy was 154 days longer than that of patients treated with chemotherapy alone (P=0.41. Conclusions. DC vaccination and CIK immunotherapy did not cause severe adverse effects, induce immune response against CRC, and prolong OS.

  17. Chemosensitive nanocomposite for conductometric detection of hydrazine and NADH

    Energy Technology Data Exchange (ETDEWEB)

    Lange, Ulrich [Institute of Analytical Chemistry, Chemo- and Biosensors, University of Regensburg, 93047 Regensburg (Germany); Mirsky, Vladimir M., E-mail: vmirsky@hs-lausitz.d [Department of Nanobiotechnology, Lausitz University of Applied Sciences, 01968 Senftenberg (Germany)

    2011-04-01

    A new chemosensitive material based on palladium nanoparticles and PEDOT-PSS is described. The composite was characterized by transmission electron microscopy, cyclic voltammetry and in situ resistance measurements. The material was applied for conductometric detection of hydrazine and NADH. Upon exposure to these analytes PEDOT is reduced leading to an increase in its conductance. This process is catalyzed by palladium. A model for description of the potential dependence of polymer conductivity was suggested, tested and applied for the development of new calibration procedure of chemiresistors based on electroactive polymers.

  18. Performance of a capillary propellant management device with hydrazine

    Science.gov (United States)

    Tegart, J. R.

    1979-01-01

    The propellant management device that was successfully used in the Viking Orbiter spacecraft was selected for the main propulsion system of the Teleoperator Retrieval System (TRS). Due to differences in the missions and different propellants, the operation of this sheet metal vane device required reverification for the TRS application. An analytical investigation was performed considering the adverse acceleration environment and the high contract angle of the hydrazine propellant. Drop tower tests demonstrated that the device would provide propellant acquisition while the TRS was docked with Skylab, but its operation would have to be supplemented through propellant settling when free-flying.

  19. 60-WATT HYDRAZINE-AIR FUEL CELL SYSTEM.

    Science.gov (United States)

    fuel cell system as presented in our Design Plan. Prior to preparation of the Design Plan, a systems analysis of the basic electrochemical system was made. From the results of this analysis, the operating parameters of the support equipment were defined and an initial selection of components made. System components defined were: the cell stack, electrolyte tank, hydrazine feed system, cooling and chemical air blowers, voltage regulator, and thermal control system. A package design was then made for these components and the final detail design completed.

  20. A rhodol-based fluorescent chemosensor for hydrazine and its application in live cell bioimaging

    Science.gov (United States)

    Tiensomjitr, Khomsan; Noorat, Rattha; Wechakorn, Kanokorn; Prabpai, Samran; Suksen, Kanoknetr; Kanjanasirirat, Phongthon; Pewkliang, Yongyut; Borwornpinyo, Suparerk; Kongsaeree, Palangpon

    2017-10-01

    A rhodol cinnamate fluorescent chemosensor (RC) has been developed for selective detection of hydrazine (N2H4). In aqueous medium, the rhodol-based probe exhibited high selectivity for hydrazine among other molecules. The addition of hydrazine triggered a fluorescence emission with 48-fold enhancement based on hydrazinolysis and a subsequent ring-opening process. The chemical probe also displayed a selective colorimetric response toward N2H4 from colorless solution to pink, readily observed by the naked eye. The detection limit of RC for hydrazine was calculated to be 300 nM (9.6 ppb). RC is membrane permeable and was successfully demonstrated to detect hydrazine in live HepG2 cells by confocal fluorescence microscopy.

  1. The plant alkaloid and anti-leukemia drug homoharringtonine sensitizes resistant human colorectal carcinoma cells to TRAIL-induced apoptosis via multiple mechanisms.

    Science.gov (United States)

    Beranova, Lenka; Pombinho, Antonio R; Spegarova, Jarmila; Koc, Michal; Klanova, Magdalena; Molinsky, Jan; Klener, Pavel; Bartunek, Petr; Andera, Ladislav

    2013-06-01

    TNF-related apoptosis-inducing ligand (TRAIL) is a pro-apoptotic ligand from the TNF-alpha family that is under consideration, along with agonistic anti-TRAIL receptor antibodies, as a potential anti-tumor agent. However, most primary human tumors are resistant to monotherapy with TRAIL apoptogens, and thus the potential applicability of TRAIL in anti-tumor therapy ultimately depends on its rational combination with drugs targeting these resistances. In our high-throughput screening for novel agents/drugs that could sensitize TRAIL-resistant colorectal cancer cells to TRAIL-induced apoptosis, we found homoharringtonine (HHT), a cephalotaxus alkaloid and tested anti-leukemia drug, to be a very effective, low nanomolar enhancer of TRAIL-mediated apoptosis/growth suppression of these resistant cells. Co-treatment of TRAIL-resistant RKO or HT-29 cells with HHT and TRAIL led to the effective induction of apoptosis and the complete elimination of the treated cells. HHT suppressed the expression of the anti-apoptotic proteins Mcl-1 and cFLIP and enhanced the TRAIL-triggered activation of JNK and p38 kinases. The shRNA-mediated down-regulation of cFLIP or Mcl-1 in HT-29 or RKO cells variably enhanced their TRAIL-induced apoptosis but it did not markedly sensitize them to TRAIL-mediated growth suppression. However, with the notable exception of RKO/sh cFLIP cells, the downregulation of cFLIP or Mcl-1 significantly lowered the effective concentration of HHT in HHT + TRAIL co-treatment. Combined HHT + TRAIL therapy also led to the strong suppression of HT-29 tumors implanted into immunodeficient mice. Thus, HHT represents a very efficient enhancer of TRAIL-induced apoptosis with potential application in TRAIL-based, anti-cancer combination therapy.

  2. Inhibitor of growth 4 suppresses colorectal cancer growth and invasion by inducing G1 arrest, inhibiting tumor angiogenesis and reversing epithelial-mesenchymal transition.

    Science.gov (United States)

    Qu, Hui; Yin, Hong; Yan, Su; Tao, Min; Xie, Yufeng; Chen, Weichang

    2016-05-01

    Previous studies have found that inhibitor of growth 4 (ING4), a tumor suppressor, is reduced in human colorectal cancer (CRC), and is inversely correlated with clinical Dukes' stage, histological grade, lymph node metastasis and microvessel density (MVD). However, its underlying mechanism remains undetermined. In the present study, we analyzed ING4 expression in a panel of human CRC cells using low (LS174T and SW480) and high (LoVo and SW620) metastatic cell lines. We demonstrated that both the low and high metastatic CRC cells exhibited a lower level of ING4 compared to the level in normal human colorectal mucous epithelial FHC cells. Furthermore, ING4 expression in high metastatic CRC cells was less than that in low metastatic CRC cells. We then generated a lentivirus construct expressing ING4 and green fluorescent protein (GFP), established a ING4-stably transgenic LoVo CRC cell line, and investigated the effect of lentiviral-mediated ING4 expression on high metastatic LoVo CRC cells. Gain-of-function studies revealed that ING4 significantly inhibited LoVo CRC cell growth and invasion in vitro and induced cell cycle G1 phase arrest. Moreover, ING4 obviously suppressed LoVo CRC subcutaneously xenografted tumor growth and reduced tumor MVD in vivo in athymic BALB/c nude mice. Mechanistically, ING4 markedly upregulated P21 and E-cadherin but downregulated cyclin E, interleukin (IL)-6, IL-8, vascular endothelial growth factor (VEGF), Snail1, N-cadherin and vimentin in the LoVo CRC cells. Our data provide compelling evidence that i) ING4 suppresses CRC growth possibly via induction of G1 phase arrest through upregulation of P21 cyclin-dependent kinase (CDK) inhibitor and downregulation of cyclin E as well as inhibition of tumor angiogenesis through reduction of IL-6, IL-8 and VEGF proangiogenic factors; ii) ING4 inhibits CRC invasion and metastasis probably via a switch from mesenchymal marker N-cadherin to epithelial marker E-cadherin through downregulation of

  3. Mapping of DNA Hypermethylation and Hypomethylation induced by Folate Deficiency in Sporadic Colorectal Cancer and Clinical Implication Analysis of Hypermethylation Pattern in CBS Promoter.

    Science.gov (United States)

    Zhang, Zaizhong; He, Yang; Tu, Xiaohuang; Huang, Sheng; Chen, Zhuo; Wang, Lie; Song, Jingxiang

    2017-04-01

    Aberrant DNA methylation patterns play a major role in tumorigenesis and the effects of nutrients, especially folate in the diet, on methylation changes is of great importance in colorectal cancer (CRC). Folate deficiency would disrupt methylation patterns; however, its exact effects on DNA methylation patterns in CRC are unclear. This study was performed to gain insight into the methylation changes induced by folate deficiency and the putative role of methylation pattern diversities of related genes in the clinical outcome of CRC. The NimbleGen MeDIP chip (Methylated DNA Immunoprecipitation chip) assay was used in high-resolution mapping of DNA methylation patterns in the normal human colon mucosal epithelial cell line, NCM460 cultured with or without folate. Aberrant CpG island methylation patterns in the promoter of genes were identified by chip assay and then were confirmed in paired colorectal tissues and corresponding non-malignant tissues obtained from patients by bisulfate sequencing PCR (BSP). Of the total, the expression of cystathionine-beta-synthase (CBS) involved in methyl metabolism and its important substrate, homocysteine, were all detected by realtime RT-PCR and immunostaining. We also analyzed the data of its hypermethylation level statistically correlated with pathological parameters and the clinical outcome in malignant tissues. The chip assay showed that there are 17 genes with hyper or hypomethylation in CpG islands of promoter on chromosome 21, and 8 of them seemed to be associated with tumorigenesis. Among the total, a hypermethylation patterns existed in the promoter of CBS in CRC (p CBS and the accumulation of homocysteine in vitro and vivo (p CBS hypermethylation level is correlated with age (p CBS hypermethylation level significantly correlated with recurrence rate (p = 0.039) and overall survival (p = 0.012) independent of pT stage, pN stage, and liver metastasis. Folate deficiency could induce aberrant DNA methylation patterns and gene

  4. DHX32 Promotes Angiogenesis in Colorectal Cancer Through Augmenting β-catenin Signaling to Induce Expression of VEGFA

    Directory of Open Access Journals (Sweden)

    Huayue Lin

    2017-04-01

    Full Text Available We previously reported that overexpression of DHX32 contributes to the growth and metastasis of colorectal cancer (CRC. However, the underlying mechanism is not largely characterized. Herein, we reported that DHX32 in CRC cells upregulated expression of vascular endothelial growth factor A (VEGFA at the transcription level through interacting with and stabilizing β-catenin. This promoted the recruitment of host endothelial cells to the tumor, and therefore, formation of microvessel in the tumor. Xenograft model revealed that depletion of DHX32 in CRC cells significantly reduced the microvessel density in the grafts and suppressed the growth of grafts. Furthermore, the expression level of DHX32 was positively associated with microvessel density in human CRC and poor outcome of CRC patients. Therefore, the report demonstrates that DHX32 is a pro-angiogenic factor, that inhibition of DHX32-β-catenin pathway can provide a strategy for CRC treatment, and that the expression level of DHX32 has the potential to serve as a biomarker for CRC diagnosis and prognosis.

  5. Dihydropyrimidine based hydrazine dihydrochloride derivatives as potent urease inhibitors.

    Science.gov (United States)

    Khan, Ajmal; Hashim, Jamshed; Arshad, Nuzhat; Khan, Ijaz; Siddiqui, Naureen; Wadood, Abdul; Ali, Muzaffar; Arshad, Fiza; Khan, Khalid Mohammed; Choudhary, M Iqbal

    2016-02-01

    Four series of heterocyclic compounds 4-dihydropyrimidine-2-thiones 7-12 (series A), N,S-dimethyl-dihydropyrimidines 13-18 (series B), hydrazine derivatives of dihydropyrimidine 19-24 (series C), and tetrazolo dihydropyrimidine derivatives 25-30 (series D), were synthesized and evaluated for in vitro urease inhibitory activity. The series B-D were first time examined for urease inhibition. Series A and C were found to be significantly active with IC50 values between 34.7-42.9 and 15.0-26.0 μM, respectively. The structure-activity relationship showed that the free S atom and hydrazine moiety are the key pharmacophores against urease enzyme. The kinetic studies of the active series A (7-12) and C (19-24) were carried out to determine their modes of inhibition and dissociation constants Ki. Compounds of series A (7-12) and series C (19-24) showed a mixed-type of inhibition with Ki values ranging between 15.76-25.66 and 14.63-29.42 μM, respectively. The molecular docking results showed that all the active compounds of both series have significant binding interactions with the active sites specially Ni-ion of the urease enzyme. Cytotoxicity of all series A-D was also evaluated against mammalian mouse fibroblast 3T3 cell lines, and no toxicity was observed in cellular model.

  6. Complexes with Mercaptosuccinic Acid and Hydrazine as Ligands

    Directory of Open Access Journals (Sweden)

    S. Devipriya

    2013-01-01

    Full Text Available Reaction of hydrazine and mercaptosuccinic acid with metal ions forms\tcomplexes with general formula [Ln(N2H42CH2(COOCH(SH(COO1.5]·(H2O, where Ln = La(III, Pr(III, Nd(III, Sm(III, and Gd(III at pH 5. The complexes have been characterized by elemental analysis, IR and UV-visible spectroscopic, thermal and X-ray diffraction studies. The IR data reveal that the acid moiety in the complexes is present as dianion due to the deprotonation of COOH groups by lanthanides in these complexes, leaving –SH group unionized and hydrazine as bidental neutral ligand showing absorptions in the range of 945–948 cm−1. The thermoanalytical data evince that the complexes are stable up to 103°C and undergo complete decomposition in the range of 550–594°C resulting in metal oxides. SEM images of La2O3 and Gd2O3 residues show their nano sized clusters suggesting that the complexes may be used as precursors for nano La2O3 and Gd2O3, respectively. X-ray powder diffraction patterns show isomorphism among the complexes. The kinetic parameters of the decomposition of the complexes have been computed by Coats-Redfern equation.

  7. Salvia fruticosa, Salvia officinalis, and rosmarinic acid induce apoptosis and inhibit proliferation of human colorectal cell lines: the role in MAPK/ERK pathway.

    Science.gov (United States)

    Xavier, Cristina P R; Lima, Cristovao F; Fernandes-Ferreira, Manuel; Pereira-Wilson, Cristina

    2009-01-01

    Epidemiological studies have shown that nutrition is a key factor in modulating sporadic colorectal carcinoma (CRC) risk. Aromatic plants of the genus Salvia (sage) have been attributed many medicinal properties, which include anticancer activity. In the present study, the antiproliferative and proapoptotic effects of water extracts of Salvia fruticosa (SF) and Salvia officinalis (SO) and of their main phenolic compound rosmarinic acid (RA) were evaluated in two human colon carcinoma-derived cell lines, HCT15 and CO115, which have different mutations in the MAPK/ERK and PI3K/Akt signalling pathways. These pathways are commonly altered in CRC, leading to increased proliferation and inhibition of apoptosis. Our results show that SF, SO, and RA induce apoptosis in both cell lines, whereas cell proliferation was inhibited by the two sage extracts only in HCT15. SO, SF, and RA inhibited ERK phosphorylation in HCT15 and had no effects on Akt phosphorylation in CO115 cells. The activity of sage extracts seems to be due, at least in part, to the inhibition of MAPK/ERK pathway.

  8. 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.

  9. Inhibition of azoxymethane-induced colorectal cancer by CP-31398, a TP53 modulator, alone or in combination with low doses of celecoxib in male F344 rats.

    Science.gov (United States)

    Rao, Chinthalapally V; Steele, Vernon E; Swamy, Malisetty V; Patlolla, Jagan M R; Guruswamy, Suresh; Kopelovich, Levy

    2009-10-15

    Tumor suppressor p53 plays a major role in colorectal cancer development. The present study explores the effects of p53-modulating agent CP-31398 alone and combined with celecoxib on azoxymethane-induced aberrant crypt foci (ACF) and colon adenocarcinomas in F344 rats. Maximum tolerated doses were 400 and 3,000 ppm for CP-31398 and celecoxib, respectively. ACF and tumor efficacy endpoints were carried out on azoxymethane-treated 7-week-old rats (48 per group) fed the control AIN-76A diet. Two weeks after carcinogen treatment, rats were fed the diets containing 0, 150, or 300 ppm CP-31398, 300 ppm celecoxib, or 150 ppm CP-31398 plus 300 ppm celecoxib. ACF and colon adenocarcinomas were determined at 8 and 48 weeks after azoxymethane treatment, respectively. Dietary CP-31398 was shown to suppress mean colonic total ACF by 43% and multicrypt ACF by 63%; dietary CP-31398 at 150 and 300 ppm suppressed adenocarcinoma incidence by 30.4% (P Rats that were fed the high-dose CP-31398 or a combination of low-dose CP-31398 and celecoxib showed considerable enhancement of p53 and p21(WAF1/CIP) expression, apoptosis, and reduced tumor cell proliferation in colonic tumors. These observations show, for the first time, that CP-31398 possesses significant dose-dependent chemopreventive activity in a well-established colon cancer model and that a combination of low-dose CP-31398 and celecoxib significantly enhanced colon cancer chemopreventive efficacy.

  10. Chemotherapy-induced suppression to adenoma or complete suppression of the primary in patients with stage IV colorectal cancer: report of four cases.

    Science.gov (United States)

    Armbrust, Thomas; Sobotta, Michael; Füzesi, Laszlo; Grabbe, Eckhardt; Ramadori, Giuliano

    2007-11-01

    Although modern chemotherapy of stage IV advanced colorectal cancer (CRC) has impressively improved overall survival, the response of the primary tumor has not been studied because surgical resection of the primary continues to be the standard procedure in stage IV CRC. Long-term follow-up of the primary in patients with stage IV CRC under chemotherapy. Here we report on the histological changes in the primary tumor in four patients suffering from stage IV CRC. Systemic chemotherapy was started immediately after endoscopic tumor debulking in three cases. In one case no endoscopic intervention was performed before chemotherapy. Neither macroscopic nor histological evidence for malignant tumor growth was found at the former site of the primary after 6, 23, 26 or 48 months, respectively. Two patients had a complete suppression of the primary, two patients had an adenoma at the former site of the primary. To date, three patients have died because of progression of liver metastases and one patient is still alive with no signs of tumor growth. The four cases illustrate that today's chemotherapy may effectively induces suppression of the primary in CRC. The development of CRC may follow different pathways.

  11. T cell responses against microsatellite instability-induced frameshift peptides and influence of regulatory T cells in colorectal cancer.

    Science.gov (United States)

    Bauer, Kathrin; Nelius, Nina; Reuschenbach, Miriam; Koch, Moritz; Weitz, Jürgen; Steinert, Gunnar; Kopitz, Jürgen; Beckhove, Philipp; Tariverdian, Mirjam; von Knebel Doeberitz, Magnus; Kloor, Matthias

    2013-01-01

    High-level microsatellite-unstable (MSI-H) colorectal carcinomas (CRC) represent a distinct subtype of tumors commonly characterized by dense infiltration with cytotoxic T cells, most likely due to expression of MSI-H-related frameshift peptides (FSP). The contribution of FSP and classical antigens like MUC1 and CEA to the cellular immune response against MSI-H CRC had not been analyzed so far. We analyzed tumor-infiltrating and peripheral T cells from MSI-H (n = 4 and n = 14, respectively) and microsatellite-stable (MSS) tumor patients (n = 26 and n = 17) using interferon gamma ELISpot assays. Responses against 4 FSP antigens and peptides derived from MUC1 to CEA were compared with and without depletion of regulatory T cells, and the results were related to the presence of the respective antigens in tumor tissue. Preexisting FSP-specific T cell responses were detected in all (4 out of 4) tumor-infiltrating and in the majority (10 out of 14) of peripheral T cell samples from MSI-H CRC patients, but rarely observed in MSS CRC patients. Preexisting T cell responses in MSI-H CRC patients were significantly more frequently directed against FSP tested in the present study than against peptides derived from classical antigens MUC1 or CEA (p = 0.049). Depletion of regulatory T cells increased the frequency of effector T cell responses specific for MUC1/CEA-derived peptides and, to a lesser extent, T cell responses specific for FSP. Our data suggest that the analyzed FSP may represent an immunologically relevant pool of antigens capable of eliciting antitumoral effector T cell responses.

  12. Activation of IRE1α-XBP1 pathway induces cell proliferation and invasion in colorectal carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Jin, Chun [Department of Coloproctology, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000 (China); Jin, Zhao [Department of Coloproctology, Wenzhou Hospital of Integrated Traditional Chinese and Western Medicine, Wenzhou 325000 (China); Chen, Nian-zhao [Department of Medicine, The Chinese Medicine Hospital of Wenzhou, Wenzhou 325000 (China); Lu, Min; Liu, Chang-bao; Hu, Wan-Le [Department of Coloproctology, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000 (China); Zheng, Chen-guo, E-mail: zhengchenguo80@163.com [Department of Coloproctology, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000 (China)

    2016-01-29

    Cell proliferation and tumor metastasis are considered as the main reasons for death in colorectal carcinoma (CRC). IRE1α-XBP1 pathway is the most conserved UPR pathways, which are activated during ER stress caused by the accumulation of unfolded or misfolded protein in the lumen of ER. Here, we demonstrated the critical role of IRE1α-XBP1 pathway and underlying molecular mechanism in cell proliferation and tumor metastasis in CRC. By the use of tissue microarray analysis of samples from 119 patients with CRC, IRE1α was determined to be an independent predictor of overall survival as higher expression of IRE1α in CRC patients showed lower survival rates (p = 0.0041). RNA interference and ectopic expression of IRE1α were applied to determine the molecular effects of IRE1α in CRC cells. The silencing of IRE1α inhibited the proliferation and blocked the invasion of CRC cells in vitro, while ectopic expression of IRE1α in turn promoted cell proliferation and invasion. IRE1α-XBP1 pathway regulated the mitosis of CRC cells through the directly binding of XBP1s to Cyclin D1 promoter to activate Cyclin D1 expression. Our results reveal that IRE1α-XBP1 pathway plays an important role in tumor progression and epithelial-to-mesenchymal transition (EMT), and IRE1α could be employed as a novel prognostic marker and a promising therapeutic target for CRC. - Highlights: • IRE1 was determined to be an independent predictor of overall survival in CRC patient. • IRE1-XBP1 pathway promoted CRC cell proliferation through regulating Cyclin D1 expression. • IRE1-XBP1 pathway played important role in EMT of CRC cells.

  13. External Qi of Yan Xin Qigong Inhibits Activation of Akt, Erk1/2 and NF-ĸB and Induces Cell Cycle Arrest and Apoptosis in Colorectal Cancer Cells

    Directory of Open Access Journals (Sweden)

    Xin Yan

    2013-01-01

    Full Text Available Background/Aims: Colorectal cancer (CRC is the second leading cause of cancer death in the Western countries. Novel approaches of treatment are needed for CRC. The purpose of the present study was to investigate cytotoxic effect of external Qi of Yan Xin Qigong (YXQ-EQ on human colorectal cancer cells. Methods: The effect of YXQ-EQ on viability, cell cycle progression and apoptosis in colorectal cancer HT-29 cells was investigated. Phosphorylation of Akt and Erk1/2, activation of NF-ĸB and the expression of proteins involved in regulation of cell cycle and apoptosis were examined by Western blot analysis. Results: YXQ-EQ markedly decreased viability and blocked colony formation of HT-29 cells. YXQ-EQ downregulated cyclin D1 expression and increased accumulation of cyclin-dependent kinase inhibitors p21Cip1 and p27Kip1, resulting in G1 cell cycle arrest. YXQ-EQ induced apoptosis in HT-29 cells in association with decreased expression of antiapoptotic proteins Bcl-xL, XIAP, survivin and Mcl-1 and elevated expression of proapoptotic protein Bax. YXQ-EQ significantly repressed phosphorylation of Akt and Erk1/2 and NF-ĸB activation in HT-29 cells, suggesting that YXQ-EQ may exert cytotoxic effect through regulating signaling pathways critical for cell proliferation and survival. Furthermore, YXQ-EQ treated PBS and an YXQ-EQ treated plant extract induced apoptosis in HT-29 cells. Conclusion: These findings show that YXQ-EQ has potent cytotoxic effect on HT-29 cells and suggest that YXQ-EQ could be potentially used for colorectal cancer treatment either directly or indirectly via carriers.

  14. Colorectal Cancer: A Personal Journey

    Science.gov (United States)

    ... of this page please turn JavaScript on. Feature: Colorectal Cancer Colorectal Cancer: A Personal Journey Past Issues / Summer 2016 Table ... Carmen Marc Valvo is an outspoken voice for colorectal cancer screening. Photo Courtesy of: Phil Fisch Photography Designer ...

  15. Human enhancer of filamentation 1-induced colorectal cancer cell migration: Role of serine phosphorylation and interaction with the breast cancer anti-estrogen resistance 3 protein.

    Science.gov (United States)

    Ibrahim, Rama; Lemoine, Antoinette; Bertoglio, Jacques; Raingeaud, Joël

    2015-07-01

    Human enhancer of filamentation 1 (HEF1) is a member of the p130Cas family of docking proteins involved in integrin-mediated cytoskeleton reorganization associated with cell migration. Elevated expression of HEF1 promotes invasion and metastasis in multiple cancer cell types. To date, little is known on its role in CRC tumor progression. HEF1 is phosphorylated on several Ser/Thr residues but the effects of these post-translational modifications on the functions of HEF1 are poorly understood. In this manuscript, we investigated the role of HEF1 in migration of colorectal adeno-carcinoma cells. First, we showed that overexpression of HEF1 in colo-carcinoma cell line HCT116 increases cell migration. Moreover, in these cells, HEF1 increases Src-mediated phosphorylation of FAK on Tyr-861 and 925. We then showed that HEF1 mutation on Ser-369 enhances HEF1-induced migration and FAK phosphorylation as a result of protein stabilization. We also, for the first time characterized a functional mutation of HEF1 on Arg-367 which mimics the effect of Ser-369 to Ala mutation. Finally through mass spectrometry experiments, we identified BCAR3 as an essential interactor and mediator of HEF1-induced migration. We demonstrated that single amino acid mutations that prevent formation of the HEF1-BCAR3 complex impair HEF1-mediated migration. Therefore, amino-acid substitutions that impede Ser-369 phosphorylation stabilize HEF1 which increases the migration of CRC cells and this latter effect requires the interaction of HEF1 with the NSP family adaptor protein BCAR3. Collectively, these data reveal the importance of HEF1 expression level in cancer cell motility and then support the utilization of HEF1 as a biomarker of tumor progression.

  16. NSC666715 and Its Analogs Inhibit Strand-Displacement Activity of DNA Polymerase β and Potentiate Temozolomide-Induced DNA Damage, Senescence and Apoptosis in Colorectal Cancer Cells.

    Directory of Open Access Journals (Sweden)

    Aruna S Jaiswal

    Full Text Available Recently approved chemotherapeutic agents to treat colorectal cancer (CRC have made some impact; however, there is an urgent need for newer targeted agents and strategies to circumvent CRC growth and metastasis. CRC frequently exhibits natural resistance to chemotherapy and those who do respond initially later acquire drug resistance. A mechanism to potentially sensitize CRC cells is by blocking the DNA polymerase β (Pol-β activity. Temozolomide (TMZ, an alkylating agent, and other DNA-interacting agents exert DNA damage primarily repaired by a Pol-β-directed base excision repair (BER pathway. In previous studies, we used structure-based molecular docking of Pol-β and identified a potent small molecule inhibitor (NSC666715. In the present study, we have determined the mechanism by which NSC666715 and its analogs block Fen1-induced strand-displacement activity of Pol-β-directed LP-BER, cause apurinic/apyrimidinic (AP site accumulation and induce S-phase cell cycle arrest. Induction of S-phase cell cycle arrest leads to senescence and apoptosis of CRC cells through the p53/p21 pathway. Our initial findings also show a 10-fold reduction of the IC50 of TMZ when combined with NSC666715. These results provide a guide for the development of a target-defined strategy for CRC chemotherapy that will be based on the mechanisms of action of NSC666715 and TMZ. This combination strategy can be used as a framework to further reduce the TMZ dosages and resistance in CRC patients.

  17. Cinnamomum verum component 2-methoxycinnamaldehyde: a novel antiproliferative drug inducing cell death through targeting both topoisomerase I and II in human colorectal adenocarcinoma COLO 205 cells

    Directory of Open Access Journals (Sweden)

    Kuen-daw Tsai

    2016-06-01

    Full Text Available Background: Cinnamomum verum is used to manufacture the spice cinnamon. In addition, the plant has been used as a Chinese herbal medication. Methods: We investigated the antiproliferative effect of 2-methoxycinnamaldehyde (2-MCA, a constituent of the cortex of the plant, and the molecular biomarkers associated with tumorigenesis in human colorectal adenocarcinoma COLO 205 cells. Specifically, cell viability was evaluated by colorimetric assay; apoptosis was determined by flow cytometry and morphological analysis with bright field, acridine orange, and neutral red stainings, as well as comet assay; topoisomerase I activity was determined by assay based upon DNA relaxation and topoisomerase II by DNA relaxation plus decatentation of kinetoplast DNA; lysosomal vacuolation and volume of acidic compartments (VACs were determined by neutral red staining. Results: The results demonstrate that 2-MCA inhibited proliferation and induced apoptosis as implicated by mitochondrial membrane potential (ΔΨm loss, activation of both caspase-3 and -9, increase of annexin V+PI+ cells, as well as morphological characteristics of apoptosis. Furthermore, 2-MCA also induced lysosomal vacuolation with elevated VAC, cytotoxicity, and inhibitions of topoisomerase I as well as II activities. Additional study demonstrated the antiproliferative effect of 2-MCA found in a nude mice model. Conclusions: Our data implicate that the antiproliferative activity of 2-MCA in vitro involved downregulation of cell growth markers, both topoisomerase I and II, and upregulation of pro-apoptotic molecules, associated with increased lysosomal vacuolation. In vivo 2-MCA reduced the tumor burden that could have significant clinical impact. Indeed, similar effects were found in other tested cell lines, including human hepatocellular carcinoma SK-Hep-1 and Hep 3B, lung adenocarcinoma A549 and squamous cell carcinoma NCI-H520, and T-lymphoblastic MOLT-3 (results not shown. Our data implicate

  18. Quercetin induces cell cycle arrest and apoptosis in CD133+ cancer stem cells of human colorectal HT29 cancer cell line and enhances anticancer effects of doxorubicin

    Science.gov (United States)

    Atashpour, Shekoufeh; Fouladdel, Shamileh; Movahhed, Tahereh Komeili; Barzegar, Elmira; Ghahremani, Mohammad Hossein; Ostad, Seyed Nasser; Azizi, Ebrahim

    2015-01-01

    Objective(s): The colorectal cancer stem cells (CSCs) with the CD133+ phenotype are a rare fraction of cancer cells with the ability of self-renewal, unlimited proliferation and resistance to treatment. Quercetin has anticancer effects with the advantage of exhibiting low side effects. Therefore, we evaluated the anticancer effects of quercetin and doxorubicin (Dox) in HT29 cancer cells and its isolated CD133+ CSCs. Materials and Methods: The CSCs from HT29 cells were isolated using CD133 antibody conjugated to magnetic beads by MACS. Anticancer effects of quercetin and Dox alone and in combination on HT29 cells and CSCs were evaluated using MTT cytotoxicity assay and flow cytometry analysis of cell cycle distribution and apoptosis induction. Results: The CD133+ CSCs comprised about 10% of HT29 cells. Quercetin and Dox alone and in combination inhibited cell proliferation and induced apoptosis in HT29 cells and to a lesser extent in CSCs. Quercetin enhanced cytotoxicity and apoptosis induction of Dox at low concentration in both cell populations. Quercetin and Dox and their combination induced G2/M arrest in the HT29 cells and to a lesser extent in CSCs. Conclusion: The CSCs were a minor population with a significantly high level of drug resistance within the HT29 cancer cells. Quercetin alone exhibited significant cytotoxic effects on HT29 cells and also increased cytoxicity of Dox in combination therapy. Altogether, our data showed that adding quercetin to Dox chemotherapy is an effective strategy for treatment of both CSCs and bulk tumor cells. PMID:26351552

  19. The effect of FAAH, MAGL, and Dual FAAH/MAGL inhibition on inflammatory and colorectal distension-induced visceral pain models in Rodents.

    Science.gov (United States)

    Sakin, Y S; Dogrul, A; Ilkaya, F; Seyrek, M; Ulas, U H; Gulsen, M; Bagci, S

    2015-07-01

    Recent studies showed that the pharmacological inhibition of endocannabinoid degrading enzymes such as fatty acid amide hydrolase (FAAH) and monoacyl glycerol lipase (MAGL) elicit promising analgesic effects in a variety of nociceptive models without serious side effects. However, the full spectrum of activities is not observed upon inhibition of either FAAH or MAGL enzymes alone and thus dual FAAH and MAGL inhibitors have been described. Visceral pain is strongly associated with inflammation and distension of the gut. Thus, we explored the comparable effects of FAAH, MAGL, and dual FAAH/MAGL inhibitors on inflammatory and mechanically evoked visceral pain models. Visceral inflammatory and distension-induced pain were assessed with the 0.6% acetic acid writhing test in mice and colorectal distension (CRD) test in rats, respectively. The selective FAAH inhibitor PF 3845, MAGL inhibitor JZL 184, dual inhibitor JZL 195, and the cannabis analog CP 55,940 were given systemically 30 min prior to nociceptive testing. PF 3845 (5, 10, and 20 mg/kg), JZL 184 (5, 10, and 20 mg/kg), and JZL 195 (5, 10, and 20 mg/kg) elicit dose-dependent antinociceptive in the acetic acid writhing test. In the CRD model, while JZL 195 (5, 10, or 20 mg/kg) and PF3845 (10, 20, and 40 mg/kg) produced dose-dependent antinociceptive effects comparable to those of CP 55,940 (0.1, 0.3, or 1 mg/kg), JZL 184 (10, 20, and 40 mg/kg) alone did not alter the visceromotor response (VMR). The selective FAAH inhibitor and dual FAAH/MAGL inhibitors were effective in both inflammatory and mechanically evoked visceral pain, while the MAGL inhibitor elicited an analgesic effect in inflammatory, but not in distension-induced, visceral pain. © 2015 John Wiley & Sons Ltd.

  20. Antisymmetric Amino-Wagging Band of Hydrazine up to K' = 13 Levels

    Science.gov (United States)

    Gulaczyk; Kr; Valentin

    1997-12-01

    A newly recorded high-resolution infrared spectrum of hydrazine has been studied in the 729-1198 cm-1 region (the nu12 antisymmetric wagging band) with a resolution of 0.002 cm-1. About 1350 transitions with K' from 7 to 13 have been newly assigned and about 2350 transitions with lower values of K' reanalyzed with the improved precision. The effective parameters have been calculated separately for each value of K' using the Hougen-Ohashi hamiltonian for hydrazine. The extended assignment completes the analysis of the nu12 band of hydrazine. Copyright 1997 Academic Press. Copyright 1997Academic Press

  1. 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....

  2. Evaluation of patients with liver metastases from colorectal cancer for locally ablative treatment with laser induced thermotherapy. Impact of PET with {sup 18}F-fluorodeoxyglucose on therapeutic decisions

    Energy Technology Data Exchange (ETDEWEB)

    Amthauer, H.; Denecke, T.; Ruehl, R.; Miersch, A.; Ruf, J.; Plotkin, M.; Haenninen, E.L.; Stroszczynski, C.; Gutberlet, M.; Ricke, J. [Klinik fuer Strahlenheilkunde und PET-Zentrum, Campus Virchow-Klinikum, Charite-Universitaetsmedizin, Berlin (Germany); Hildebrandt, B.; Nicolaou, A.; Riess, H. [Medizinische Klinik fuer Haematologie Onkologie, Campus Virchow-Klinikum, Charite-Universitaetsmedizin, Berlin (Germany); Langrehr, J. [Klinik fuer Allgemein-, Viszeral- und Transplantationschirurgie, Campus Virchow-Klinikum, Charite-Universitaetsmedizin, Berlin (Germany)

    2006-07-01

    Purpose: before locally ablative treatment of colorectal liver metastases, patients have to be carefully evaluated to decide whether this is the adequate therapy. In this study we determined the value of FDG-PET in comparison to conventional staging procedures. Patients, methods: in 68 consecutive patients referred for laser induced thermotherapy (LITT) of liver metastases from colorectal cancer, pre-therapeutic staging with conventional imaging (thoracic and abdominal CT, liver MRI, chest X-ray) and FDG-PET was performed. The examinations were analysed separately and blinded. Based on the staging information, therapeutic decisions were made by an interdisciplinary review board according to a standardized algorithm. The results were compared between conventional imaging and FDG-PET, and were validated by clinical follow up data and histopathology, respectively. Results: on FDG-PET 210 lesions were interpreted as tumour manifestations. 48 of these were not seen on conventional imaging (true positive, n = 46). In contrast, 24 lesions were visualized by conventional imaging only (true positive, n = 12). Compared to conventional imaging, discrepant findings on FDG-PET led to treatment modifications in 25 patients (37%); these were correct in 20/25 patients. According to the actual treatment course, the inadequate treatment modifications in the remaining 5 patients were avoided by further diagnostic procedures (i.e. biopsies). Conclusions: In the evaluation of patients with known liver metastases from colorectal cancer before LITT, FDG-PET depicts relevant findings subsidiary to conventional imaging and thus is of high value for therapeutic decision making. (orig.)

  3. Platinum-(Ⅳ)-derivative satraplatin induced G2/M cell cycle perturbation via p53-p21waf1/cip1-independent pathway in human colorectal cancer cells

    Institute of Scientific and Technical Information of China (English)

    Murugan KALIMUTHO; Antonella MINUTOLO; Sandro GRELLI; Giorgio FEDERICI; Sergio BERNARDINI

    2011-01-01

    Aim:Platinum-(Ⅳ)-derivative satraplatin represents a new generation of orally available anti-cancer drugs that are under development for the treatment of several cancers.Understanding the mechanisms of cell cycle modulation and apoptosis is necessary to define the mode of action of satraplatin.In this study,we investigate the ability of satraplatin to induce cell cycle perturbation,clonogenicity loss and apoptosis in colorectal cancer (CRC) cells.Methods:CRC cells were treated with satraplatin,and the effects of satraplatin on apoptosis and the cell cycle were evaluated by flow cytometry.Western blot analysis was used to investigate the effects of satraplatin on cell cycle and apoptosis-related proteins.RTqPCR was used to evaluate p53-related mRNA modulation.Results:Satraplatin induced an accumulation of CRC cells predominantly in the G2/M phase.Increased p53 protein expression was observed in the p53 wild-type HCT116 and LoVo cells together with p21waf1/cip1 protein up-regulation.However,p21waf1/cip1 protein accumulation was not observed in the p53 mutant HCT15,HT29,and WiDr cells,even when p53 protein expression was compromised,suggesting that the cell cycle perturbation is p53-p21waf1/cip1 independent.Following a candidate approach,we found an elevated expression of 14-3-3o protein levels in CRC cells,which was independent of the status of p53,further supporting the role of satraplatin in the perturbation of the G2/M cell cycle phase.Moreover,satraplatin treatment induced apoptosis along with Bcl-2 protein down-regulation and abrogated the clonogenic formation of CRC cells in vitro.Conclusion:Collectively,our data suggest that satraplatin induces apoptosis in CRC cells,which is preceded by cell cycle arrest at G2/M due to the effect of 14-3-3σ and in a p53-p21waf1/cip1-independent manner.Taken together,these findings highlight the potential use of satraplatin for CRC treatment.

  4. Detection of Copper(II) Ions Using Glycine on Hydrazine-Adsorbed Gold Nanoparticles via Raman Spectroscopy

    Science.gov (United States)

    Ly, Nguyễn Hoàng; Seo, Chulhun; Joo, Sang-Woo

    2016-01-01

    A facile, selective, and sensitive detection method for the Cu2+ ions in environmental and biological solutions has been newly developed by observing the unique CN stretching peaks at ~2108 cm−1 upon the dissociative adsorption of glycine (GLY) in hydrazine buffer on gold nanoparticles (AuNPs). The relative abundance of Cu species on AuNPs was identified from X-ray photoelectron spectroscopy analysis. UV-Vis spectra also indicated that the Au particles aggregated to result in the color change owing to the destabilization induced by the GLY-Cu2+ complex. The CN stretching band at ~2108 cm−1 could be observed to indicate the formation of the CN species from GLY on the hydrazine-covered AuNP surfaces. The other ions of Fe3+, Fe2+, Hg2+, Mg2+, Mn2+, Ni2+, Zn2+, Cr3+, Co2+, Cd2+, Pb2+, Ca2+, NH4+, Na+, and K+ at high concentrations of 50 µM did not produce such spectral changes. The detection limit based on the CN band for the determination of the Cu2+ ion could be estimated to be as low as 500 nM in distilled water and 1 µM in river water, respectively. We attempted to apply our method to estimate intracellular ion detection in cancer cells for more practical purposes. PMID:27792178

  5. 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

  6. Tissue Specific Promoters in Colorectal Cancer

    Directory of Open Access Journals (Sweden)

    A. R. Rama

    2015-01-01

    Full Text Available Colorectal carcinoma is the third most prevalent cancer in the world. In the most advanced stages, the use of chemotherapy induces a poor response and is usually accompanied by other tissue damage. Significant progress based on suicide gene therapy has demonstrated that it may potentiate the classical cytotoxic effects in colorectal cancer. The inconvenience still rests with the targeting and the specificity efficiency. The main target of gene therapy is to achieve an effective vehicle to hand over therapeutic genes safely into specific cells. One possibility is the use of tumor-specific promoters overexpressed in cancers. They could induce a specific expression of therapeutic genes in a given tumor, increasing their localized activity. Several promoters have been assayed into direct suicide genes to cancer cells. This review discusses the current status of specific tumor-promoters and their great potential in colorectal carcinoma treatment.

  7. Tissue Specific Promoters in Colorectal Cancer

    Science.gov (United States)

    Rama, A. R.; Aguilera, A.; Melguizo, C.; Caba, O.; Prados, J.

    2015-01-01

    Colorectal carcinoma is the third most prevalent cancer in the world. In the most advanced stages, the use of chemotherapy induces a poor response and is usually accompanied by other tissue damage. Significant progress based on suicide gene therapy has demonstrated that it may potentiate the classical cytotoxic effects in colorectal cancer. The inconvenience still rests with the targeting and the specificity efficiency. The main target of gene therapy is to achieve an effective vehicle to hand over therapeutic genes safely into specific cells. One possibility is the use of tumor-specific promoters overexpressed in cancers. They could induce a specific expression of therapeutic genes in a given tumor, increasing their localized activity. Several promoters have been assayed into direct suicide genes to cancer cells. This review discusses the current status of specific tumor-promoters and their great potential in colorectal carcinoma treatment. PMID:26648599

  8. Remediation of Cr(VI)-Contaminated Soil Using the Acidified Hydrazine Hydrate.

    Science.gov (United States)

    Ma, Yameng; Li, Fangfang; Jiang, Yuling; Yang, Weihua; Lv, Lv; Xue, Haotian; Wang, Yangyang

    2016-09-01

    Acidified hydrazine hydrate was used to remediate Cr(VI)-contaminated soil. The content of water-soluble Cr(VI) in contaminated soil was 4977.53 mg/kg. The optimal initial pH of hydrazine hydrate solution, soil to solution ratio and molar ratio of Cr(VI) to hydrazine hydrate for remediation of Cr(VI)-contaminated soil were 5.0, 3:1 and 1:3, respectively. Over 99.50 % of water-soluble Cr(VI) in the contaminated soil was reduced at the optimal condition within 30 min. The remediated soil can keep stable within 4 months. Meanwhile the total phosphorus increased from 0.47 to 4.29 g/kg, indicating that using of acidified hydrazine hydrate is an effective method to remediate Cr(VI)-contaminated soil.

  9. Au(I)-Catalyzted Synthesis of 5-Bromodifluoromethyl Pyrazoles from Fluorinated Alkynyl Ketones and Hydrazine

    Institute of Scientific and Technical Information of China (English)

    李珊; 李正珂; 彭东杰; 李亚军; 祝江涛; 解海波; 袁雅芬; 陈资衔; 吴永明

    2011-01-01

    Fluorinated alkynyl ketones react with hydrazine to give fluorinated pyrazols in good to excellent yields with Au(I) as catalyst. All the reactions were carried out at room temperature with excellent regioselectivity.

  10. U.S. experience with hydrazine and flow-accelerated corrosion

    Energy Technology Data Exchange (ETDEWEB)

    Merilo, M.; Munson, D.; Horowitz, J.S. [EPRI US (United States); Bouchacourt, M. [EDF France (France)

    2002-07-01

    Flow-accelerated corrosion (FAC) has been studied intensely for the last 30 years. In most regards, the parametric behavior of FAC has been well understood since the eighties. However, recent experience showing the impact of hydrazine has challenged this understanding. Until the early 1990's, hydrazine levels at most U.S. PWRs had been low, typically around 20 ppb. Since the mid 1990's the U.S. trend has been to increase hydrazine concentration (> 100 ppb) to provide further protection the steam generators tubes from stress corrosion cracking. In the last five years, high concentrations of hydrazine have been shown in the laboratory to affect the rate of FAC. These experiments have demonstrated this effect although there remains considerable scatter in the data supporting this conclusion. It is believed that the impact of hydrazine is due to the change in the oxidizing-reducing potential of the solution, but there is no generally accepted theory to completely describe its behavior. Recently, plant experience has begun to support the laboratory data that high hydrazine does increase the rate of FAC. It should be noted that there are several factors affecting the rate of FAC. Since most plants have changed their water chemistry in recent years, it has been difficult to ''back-out'' the influence of hydrazine. But now, plant experience has clearly shown the impact of high hydrazine especially in the high temperature portions of the feedwater piping. This has been seen at two PWRs, discussed below, and perhaps at several others. This accelerated thinning of the feedwater piping is especially significant since feedwater piping is particularly expensive to inspect and to replace. In addition to the experience with piping, there has also been degradation reported in steam generators, particularly at Gravelines in France, possibly linked to high hydrazine. In order to deal with this issue, the EPRI computer program CHECWORKS was modified in

  11. Characterization of azoxymethane-induced colon tumor metastasis to lung in a mouse model relevant to human sporadic colorectal cancer and evaluation of grape seed extract efficacy.

    Science.gov (United States)

    Derry, Molly M; Raina, Komal; Agarwal, Rajesh; Agarwal, Chapla

    2014-08-01

    The second leading cause of cancer-related deaths (both genders combined) in the United States is colorectal cancer (CRC). This emphasizes the need to develop both effective therapies for CRC patients and pre-clinical models mimicking human disease that carry translational potential in drug-development. Notably, at present there are no in situ models of CRC metastasis to lung. In our azoxymethane-induced colon tumorigenesis study in A/J mice assessing grape seed extract (GSE) efficacy, during necropsy we also found multiple lung nodules suggestive of colon tumor metastasis to lung that were significantly inhibited in GSE fed group. Both histopathological and molecular studies were performed to characterize and establish the origin of these lesions in lung. Histologically these nodules were determined as adenocarcinoma of mucin origin. Molecular analyses by immunohistochemistry (IHC) and RT-PCR revealed strong protein and transcript levels of colon specific markers CDX2 and CK20 in these lung nodules compared to uninvolved control lung tissue. Vis-à-vis, these nodules also showed minimally expressed lung specific biomarkers, specifically surfactant D and TTF-1, in IHC analysis. Additionally, 0.25% GSE supplementation in diet (w/w) decreased the incidence of these lung nodules by 53% and their total number by 66%. Together, the characterization of this unique in situ mouse model of CRC metastasis to lung provides translational opportunities in developing effective therapies to clinically manage and treat CRC at the advanced stage. Moreover, GSE efficacy in inhibiting CRC metastasis to lung in this model further supports its translational potential in controlling CRC growth, progression and metastasis in patients. Copyright © 2014 Elsevier GmbH. All rights reserved.

  12. Increased tumour ascorbate is associated with extended disease-free survival and decreased hypoxia-inducible factor-1 activation in human colorectal cancer

    Directory of Open Access Journals (Sweden)

    Caroline eKuiper

    2014-02-01

    Full Text Available Ascorbate is a co-factor for the hydroxylases that regulate the transcription factor hypoxia-inducible factor (HIF-1, which provides cancer cells with a metabolic and survival advantage in the hypoxic environment of solid tumors. However, whether ascorbate affects tumor development is a highly debated issue. We aimed to determine whether tumor ascorbate was associated with HIF-1 activation and patient disease-free survival. In this study we undertook a retrospective observational analysis of tissue-banked tumor and paired normal tissue from 49 colorectal cancer patients, measuring ascorbate levels, HIF-1α and its downstream gene products BNIP3 and VEGF. Patient survival was monitored for the first six years after surgery. We found that ascorbate levels were lower in tumor tissue compared to normal tissue (p< 0.001 but overall levels varied considerably. HIF-1α, VEGF and BNIP3 were elevated in tumor samples (p< 0.01. There was an inverse relationship between tumor ascorbate content and HIF-1 pathway activation (p=0.002 and tumor size (p=0.018. Higher tumor ascorbate content was associated with significantly improved disease-free survival in the first 6 years after surgery (p=0.006, with 141 - 1,094 additional disease free days. This was independent of tumor grade and stage. Survival advantage was associated with the amount of ascorbate in the tumor, but not with the amount in adjacent normal tissue. Our results demonstrate that higher tumor ascorbate content is associated decreased HIF-1 activation, most likely due to the co-factor activity of ascorbate for the regulatory HIF hydroxylases. Our findings support the need for future studies to determine whether raising tumor ascorbate is possible with clinical intervention and whether this results in modification of hydroxylase-dependent pathways in the tumor.

  13. Increased Tumor Ascorbate is Associated with Extended Disease-Free Survival and Decreased Hypoxia-Inducible Factor-1 Activation in Human Colorectal Cancer.

    Science.gov (United States)

    Kuiper, Caroline; Dachs, Gabi U; Munn, Delwyn; Currie, Margaret J; Robinson, Bridget A; Pearson, John F; Vissers, Margreet C M

    2014-01-01

    Ascorbate is a co-factor for the hydroxylases that regulate the transcription factor hypoxia-inducible factor (HIF)-1, which provides cancer cells with a metabolic and survival advantage in the hypoxic environment of solid tumors. However, whether ascorbate affects tumor development is a highly debated issue. We aimed to determine whether tumor ascorbate was associated with HIF-1 activation and patient disease-free survival. In this study, we undertook a retrospective observational analysis of tissue-banked tumor and paired normal tissue from 49 colorectal cancer patients, measuring ascorbate levels, HIF-1α and its downstream gene products BNIP3, and vascular endothelial cell growth factor (VEGF). Patient survival was monitored for the first 6 years after surgery. We found that ascorbate levels were lower in tumor tissue compared to normal tissue (p ascorbate content and HIF-1 pathway activation (p = 0.002) and tumor size (p = 0.018). Higher tumor ascorbate content was associated with significantly improved disease-free survival in the first 6 years after surgery (p = 0.006), with 141-1,094 additional disease-free days. This was independent of tumor grade and stage. Survival advantage was associated with the amount of ascorbate in the tumor, but not with the amount in adjacent normal tissue. Our results demonstrate that higher tumor ascorbate content is associated with decreased HIF-1 activation, most likely due to the co-factor activity of ascorbate for the regulatory HIF hydroxylases. Our findings support the need for future studies to determine whether raising tumor ascorbate is possible with clinical intervention and whether this results in modification of hydroxylase-dependent pathways in the tumor.

  14. Positional mapping and candidate gene analysis of the mouse Ccs3 locus that regulates differential susceptibility to carcinogen-induced colorectal cancer.

    Directory of Open Access Journals (Sweden)

    Charles Meunier

    Full Text Available The Ccs3 locus on mouse chromosome 3 regulates differential susceptibility of A/J (A, susceptible and C57BL/6J (B6, resistant mouse strains to chemically-induced colorectal cancer (CRC. Here, we report the high-resolution positional mapping of the gene underlying the Ccs3 effect. Using phenotype/genotype correlation in a series of 33 AcB/BcA recombinant congenic mouse strains, as well as in groups of backcross populations bearing unique recombinant chromosomes for the interval, and in subcongenic strains, we have delineated the maximum size of the Ccs3 physical interval to a ∼2.15 Mb segment. This interval contains 12 annotated transcripts. Sequencing of positional candidates in A and B6 identified many either low-priority coding changes or non-protein coding variants. We found a unique copy number variant (CNV in intron 15 of the Nfkb1 gene. The CNV consists of two copies of a 54 bp sequence immediately adjacent to the exon 15 splice site, while only one copy is found in CRC-susceptible A. The Nfkb1 protein (p105/p50 expression is much reduced in A tumors compared to normal A colonic epithelium as analyzed by immunohistochemistry. Studies in primary macrophages from A and B6 mice demonstrate a marked differential activation of the NfκB pathway by lipopolysaccharide (kinetics of stimulation and maximum levels of phosphorylated IκBα, with a more robust activation being associated with resistance to CRC. NfκB has been previously implicated in regulating homeostasis and inflammatory response in the intestinal mucosa. The interval contains another positional candidate Slc39a8 that is differentially expressed in A vs B6 colons, and that has recently been associated in CRC tumor aggressiveness in humans.

  15. LncRNA CHRF-induced miR-489 loss promotes metastasis of colorectal cancer via TWIST1/EMT signaling pathway.

    Science.gov (United States)

    Tao, Youmao; Han, Tao; Zhang, Tao; Ma, Chong; Sun, Caixia

    2017-05-30

    microRNA-489 (miR-489) is a novel cancer-related miRNAs and functions as a tumor suppressor in human cancers. While, the clinical significance of miR-489 and its role in colorectal cancer (CRC) remain rarely known. Here, we found that the levels of miR-489 in CRC tissues were significantly lower than those in matched tumor-adjacent tissues. Furthermore, decreased levels of miR-489 also observed in CRC cell lines compared to HIEC cells. Clinicopathological analysis revealed that miR-489 underexpression was positively correlated with advanced pT stage, pN stage and AJCC stage. Moreover, miR-489 low expressing CRC patients showed a obvious shorter survival. Functionally, miR-489 restoration inhibited cell migration and invasion as well as epithelial-mesenchymal transition (EMT) in HCT116 cells, while miR-489 loss facilitated these cellular processes in SW480 cells. In vivo experiments revealed that miR-489 overexpression reduced the number of metastatic nodules in nude mice liver. Notably, TWIST1 was recognized as a direct downstream target of miR-489 in CRC cells. Interestingly, TWIST1 restoration abrogated the effects of miR-489 on CRC cells with enhanced cell migration, invasion and EMT process. Furthermore, overexpression of long noncoding RNA cardiac hypertrophy-related factor (lncRNA CHRF) was inversely correlated with miR-489 expression in CRC tissues. CHRF knockdown increased the expression of miR-489 and suppressed EMT events of HCT116 cells, while CHRF overexpression showed opposite effects on miR-489 expression and EMT in SW480 cells. Taken together, this work support the first evidence that lncRNA CHRF-induced miR-489 loss facilitates metastasis and EMT process of CRC cells probably via TWIST1/EMT signaling pathway.

  16. The glutamate transport inhibitor DL-Threo-β-Benzyloxyaspartic acid (DL-TBOA) differentially affects SN38- and oxaliplatin-induced death of drug-resistant colorectal cancer cells

    DEFF Research Database (Denmark)

    Cuesta, Elena Pedraz; Christensen, Sandra; Jensen, Anders A.

    2015-01-01

    BACKGROUND: Colorectal cancer (CRC) is a leading cause of cancer death globally and new biomarkers and treatments are severely needed. METHODS: Here, we employed HCT116 and LoVo human CRC cells made resistant to either SN38 or oxaliplatin, to investigate whether altered expression of the high...... cell resistance per se correlated with increased cellular GSH. DL-TBOA did not significantly alter cellular levels of p21, cleaved PARP-1, or phospho-Retinoblastoma protein, yet altered SLC1A1 subcellular localization, and reduced chemotherapy-induced p53 induction. CONCLUSIONS: SLC1A1 expression...... and glutamate transporter activity are altered in SN38-resistant CRC cells. Importantly, the non-selective glutamate transporter inhibitor DL-TBOA reduces chemotherapy-induced p53 induction and augments CRC cell death induced by SN38, while attenuating that induced by oxaliplatin. These findings may point...

  17. Propellant Grade Hydrazine in Mono/Bi-propellant Thrusters: Preparation and Performance Evaluation

    Directory of Open Access Journals (Sweden)

    S. Krishnamachary

    2015-03-01

    Full Text Available Propellant grade hydrazine was prepared with 64 per cent yield and 95.5 per cent purity. Purity of the propellant grade hydrazine was determined using wet chemical, gas chromatographic (GC and eudiometric methods. It was observed that the compositions containing blends of hydrazine-methyl alcohol-ammonium nitrate and hydrazine-methyl alcohol-ammonium perchlorate were not found to be frozen even after cooling to -65 °C for 30 minutes. Mono and bi-propellant thrusters were designed and developed to demonstrate the performance of prepared propellant grade hydrazine as a promising rocket fuel. Five static tests with 22 N thruster and one static test with 1 N thruster were performed successfully in mono-propellant mode. The hurdles of chamber pressure oscillations were overcome by compact packing of the catalyst. The desired decomposition and chamber pressure were achieved. One static test was performed successfully with 60 N bi-propellant thruster. The desired chamber pressure and thrust were achieved. The combustion was smooth and C* achieved was higher than that of UH-25, N2O4 combination. The performance of prepared propellant grade hydrazine shows it as a promising rocket fuels.Defence Science Journal, Vol. 65, No. 1, January 2015, pp.31-38, DOI:http://dx.doi.org/10.14429/dsj.65.7986

  18. Hydrazine selective dual signaling chemodosimetric probe in physiological conditions and its application in live cells

    Energy Technology Data Exchange (ETDEWEB)

    Nandi, Sandip; Sahana, Animesh; Mandal, Sandip [Department of Chemistry, The University of Burdwan, Burdwan, 713104 West Bengal (India); Sengupta, Archya; Chatterjee, Ansuman [Department of Zoology, Visva Bharati University, Santiniketan, West Bengal (India); Safin, Damir A., E-mail: damir.a.safin@gmail.com [Institute of Condensed Matter and Nanosciences, Molecules, Solids and Reactivity (IMCN/MOST), Université catholique de Louvain, Place L. Pasteur 1, 1348 Louvain-la-Neuve (Belgium); Babashkina, Maria G.; Tumanov, Nikolay A.; Filinchuk, Yaroslav [Institute of Condensed Matter and Nanosciences, Molecules, Solids and Reactivity (IMCN/MOST), Université catholique de Louvain, Place L. Pasteur 1, 1348 Louvain-la-Neuve (Belgium); Das, Debasis, E-mail: ddas100in@yahoo.com [Department of Chemistry, The University of Burdwan, Burdwan, 713104 West Bengal (India)

    2015-09-17

    A rhodamine–cyanobenzene conjugate, (E)-4-((2-(3′,6′-bis(diethylamino)-3-oxospiro[isoindoline-1,9′-xanthene] -2-yl)ethylimino)methyl)benzonitrile (1), which structure has been elucidated by single crystal X-ray diffraction, was synthesized for selective fluorescent “turn-on” and colorimetric recognition of hydrazine at physiological pH 7.4. It was established that 1 detects hydrazine up to 58 nM. The probe is useful for the detection of intracellular hydrazine in the human breast cancer cells MCF-7 using a fluorescence microscope. Spirolactam ring opening of 1, followed by its hydrolysis, was established as a probable mechanism for the selective sensing of hydrazine. - Highlights: • A selective rhodamine–cyanobenzene conjugate is synthesized. • The conjugate is a selective dual signaling chemodosimetric probe towards hydrazine. • Spirolactam ring opening of the probe, followed by its hydrolysis, is the sensing mechanism. • The probe detects hydrazine in the human breast cancer cells MCF-7 imaging.

  19. Preparation of hydrazine functionalized polymer brushes hybrid magnetic nanoparticles for highly specific enrichment of glycopeptides.

    Science.gov (United States)

    Huang, Guang; Sun, Zhen; Qin, Hongqiang; Zhao, Liang; Xiong, Zhichao; Peng, Xiaojun; Ou, Junjie; Zou, Hanfa

    2014-05-07

    Hydrazide chemistry is a powerful technique in glycopeptides enrichment. However, the low density of the monolayer hydrazine groups on the conventional hydrazine-functionalized magnetic nanoparticles limits the efficiency of glycopeptides enrichment. Herein, a novel magnetic nanoparticle grafted with poly(glycidyl methacrylate) (GMA) brushes was fabricated via reversible addition-fragmentation chain transfer (RAFT) polymerization, and a large amount of hydrazine groups were further introduced to the GMA brushes by ring-opening the epoxy groups with hydrazine hydrate. The resulting magnetic nanoparticles (denoted as Fe3O4@SiO2@GMA-NHNH2) demonstrated the high specificity of capturing glycopeptides from a tryptic digest of the sample comprising a standard non-glycosylated protein bovine serum albumin (BSA) and four standard glycoproteins with a weight ratio of 50 : 1, and the detection limit was as low as 130 fmol. In the analysis of a real complex biological sample, the tryptic digest of hepatocellular carcinoma, 179 glycosites were identified by the Fe3O4@SiO2@GMA-NHNH2 nanoparticles, surpassing that of 68 glycosites by Fe3O4@SiO2-single-NHNH2 (with monolayer hydrazine groups on the surface). It can be expected that the magnetic nanoparticles modified with hydrazine functionalized polymer brushes via RAFT technique will improve the specificity and the binding capacity of glycopeptides from complex samples, and show great potential in the analysis of protein glycosylation in biological samples.

  20. Epstein-Barr Virus-Induced Gene 3 (EBI3) Blocking Leads to Induce Antitumor Cytotoxic T Lymphocyte Response and Suppress Tumor Growth in Colorectal Cancer by Bidirectional Reciprocal-Regulation STAT3 Signaling Pathway

    Science.gov (United States)

    Liang, Yanfang; Chen, Qianqian; Du, Wenjing; Chen, Can; Li, Feifei; Yang, Jingying; Peng, Jianyu; Kang, Dongping; Lin, Bihua; Chai, Xingxing; Zhou, Keyuan; Zeng, Jincheng

    2016-01-01

    Epstein-Barr virus-induced gene 3 (EBI3) is a member of the interleukin-12 (IL-12) family structural subunit and can form a heterodimer with IL-27p28 and IL-12p35 subunit to build IL-27 and IL-35, respectively. However, IL-27 stimulates whereas IL-35 inhibits antitumor T cell responses. To date, little is known about the role of EBI3 in tumor microenvironment. In this study, firstly we assessed EBI3, IL-27p28, IL-12p35, gp130, and p-STAT3 expression with clinicopathological parameters of colorectal cancer (CRC) tissues; then we evaluated the antitumor T cell responses and tumor growth with a EBI3 blocking peptide. We found that elevated EBI3 may be associated with IL-12p35, gp130, and p-STAT3 to promote CRC progression. EBI3 blocking peptide promoted antitumor cytotoxic T lymphocyte (CTL) response by inducing Granzyme B, IFN-γ production, and p-STAT3 expression and inhibited CRC cell proliferation and tumor growth to associate with suppressing gp130 and p-STAT3 expression. Taken together, these results suggest that EBI3 may mediate a bidirectional reciprocal-regulation STAT3 signaling pathway to assist the tumor escape immune surveillance in CRC. PMID:27247488

  1. 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 8 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, hs...

  2. [Obesity and colorectal cancer].

    Science.gov (United States)

    Na, Soo-Young; Myung, Seung-Jae

    2012-01-01

    Obesity worldwide is constantly increasing. Obesity acts as an independent significant risk factor for malignant tumors of various organs including colorectal cancer. Visceral adipose tissue is physiologically more important than subcutaneous adipose tissue. The relative risk of colorectal cancer of obese patients is about 1.5 times higher than the normal-weight individuals, and obesity is also associated with premalignant colorectal adenoma. The colorectal cancer incidence of obese patients has gender-specific and site-specific characteristics that it is higher in men than women and in the colon than rectum. Obesity acts as a risk factor of colorectal carcinogenesis by several mechanisms. Isulin, insulin-like growth factor, leptin, adiponectin, microbiome, and cytokines of chronic inflammation etc. have been understood as its potential mechanisms. In addition, obesity in patients with colorectal cancer negatively affects the disease progression and response of chemotherapy. Although the evidence is not clear yet, there are some reports that weight loss as well as life-modification such as dietary change and physical activity can reduce the risk of colorectal cancer. It is very important knowledge in the point that obesity is a potentially modifiable risk factor that can alter the incidence and outcome of the colorectal cancer.

  3. Colorectal cancers choosing sides

    NARCIS (Netherlands)

    Albuquerque, Cristina; Bakker, Elvira R. M.; van Veelen, Wendy; Smits, Ron

    2011-01-01

    In contrast to the majority of sporadic colorectal cancer which predominantly occur in the distal colon, most mismatch repair deficient tumours arise at the proximal side. At present, these regional preferences have not been explained properly. Recently, we have screened colorectal tumours for mutat

  4. Obesity and Colorectal Cancer.

    Science.gov (United States)

    Jochem, Carmen; Leitzmann, Michael

    There is strong evidence that modifiable lifestyle factors such as obesity play a key role in colorectal carcinogenesis. Epidemiologic data have consistently reported a positive association between obesity and colorectal cancer. The relative risk associated with general obesity (as assessed by BMI) is higher in men than in women and for cancer of the colon than for cancer of the rectum. Abdominal obesity (as assessed by waist circumference (WC) or waist-to-hip ratio) is associated with an increased risk of colorectal cancer in both sexes, with stronger associations for cancer of the colon than for cancer of the rectum. Plausible biological mechanisms include insulin resistance, hyperinsulinemia, chronic inflammation, altered levels of growth factors, adipocytokines and steroid hormones. In addition to its effect on colorectal cancer incidence, obesity may play a role in colorectal cancer recurrence, treatment outcomes and survival. Understanding the effects of childhood and adolescent obesity and weight change over the life course in relation to future risk of colorectal cancer is incomplete but essential for targeted preventive recommendations. This chapter summarizes the current evidence on the relationship between obesity and colorectal cancer and colorectal adenoma, a common precursor lesion.

  5. Peroxiredoxins in colorectal neoplasms

    OpenAIRE

    Wu, X.Y.; Fu, X.Z.; Wang, X. H.

    2010-01-01

    Peroxiredoxins (Prxs) are novel group proteins with efficient antioxidant capacity, and some of them also have effects on cell proliferation, differentiation, apoptosis, and chemotherapy and radiotherapy resistance. Altogether six distinct Prxs expressions were investigated in histological samples of colorectal neoplasm and the distant normal tissues and investigated associatedly with parameters such as clinical stage and lymphnodes metastasis. Normal colorectal tis...

  6. Cruciferous vegetables and colo-rectal cancer.

    OpenAIRE

    Lynn, Anthony; Collins, Andrew; Fuller, Zoë; Hillman, Kevin; Ratcliffe, Brian

    2006-01-01

    KEYWORDS - CLASSIFICATION: administration & dosage;Anticarcinogenic Agents;Apoptosis;Brassicaceae;chemically induced;chemistry;Cell Division;Colorectal Neoplasms;drug effects;dietary modulation of cancer & cancer biomarkers;Evaluation;Food Handling;Glucosinolates;Glycoside Hydrolases;Humans;Hydrolases;Isothiocyanates;metabolism;methods;pharmacology;prevention & control;Research. Cruciferous vegetables have been studied extensively for their chemoprotective effects. Although they contain ma...

  7. Pharmacokinetics of 5-fluorouracil and increased hepatic dihydropyrimidine dehydrogenase activity levels in 1,2-dimethylhydrazine-induced colorectal cancer model rats.

    Science.gov (United States)

    Kobuchi, Shinji; Ito, Yukako; Okada, Kae; Imoto, Kazuki; Takada, Kanji

    2013-09-01

    To investigate the hepatic dihydropyrimidine dehydrogenase (DPD) activity in colorectal cancer (CRC), which is critically important to create a patient-specific dosing regimen, we performed 5-FU pharmacokinetic studies in 1,2-dimethylhydrazine-induced CRC model rats (CRC rats). After rats received 5-FU intravenous (IV) bolus injections, the area under the plasma concentration-time curve (AUC) and elimination half-life (t 1/2) in CRC rats (10.02 ± 0.37 μg h mL(-1), 0.30 ± 0.02 h, respectively) were significantly lower than that in control rats (13.46 ± 1.20 μg h mL(-1), 0.52 ± 0.05 h, respectively), whereas total plasma clearance (CLtot) in CRC rats (2.01 ± 0.07 L h(-1) kg(-1)) was significantly increased compared with that in control rats (1.54 ± 0.14 L h(-1) kg(-1)). Conversely, the avoidance ratio of the hepatic first-pass effect was approximately 20 % lower than that in control rats. Of interest is that hepatic DPD activity levels and the dihydrouracil-uracil ratio (UH2/Ura ratio) in plasma, which may act as a potential biomarker to evaluate hepatic DPD activity levels, were significantly increased in CRC rats. These results suggest that the decrease of hepatic availability in CRC rats is brought about by the increase in intrinsic clearance induced by the increase in DPD activity, resulting in a decrease in AUC and t 1/2 and an increase in CLtot after 5-FU IV bolus injection. Along with a proper dosing regimen for patients with CRC, a hepatic DPD activity monitoring system, such as the determination of UH2/Ura ratio in plasma, is desirable.

  8. The antinociceptive effect of intravenous imipramine in colorectal distension-induced visceral pain in rats: the role of serotonergic and noradrenergic receptors.

    Science.gov (United States)

    İlkaya, Fatih; Bilge, S Sırrı; Bozkurt, Ayhan; Baş, Duygu B; Erdal, Arzu; Çiftçioğlu, Engin; Kesim, Yüksel

    2014-07-01

    It has been shown that imipramine, a tricyclic antidepressant (TCA), is a potent analgesic agent. However, the effect of imipramine on visceral pain has not been extensively investigated. In the current study, our aim was to characterise the putative analgesic effect of intravenous imipramine on visceral pain in rats. Our second aim was to assess the involvement of serotonergic (5-HT₂,₃,₄) and noradrenergic (α(2A, 2B, 2C)) receptor subtypes in this putative antinociceptive effect of imipramine. Male Sprague Dawley rats (250-300 g) were implanted with venous catheters for drug administration and implanted with enamelled nichrome electrodes for electromyography of the external oblique muscles. Noxious visceral stimulation was applied via by colorectal distension (CRD). The visceromotor responses (VMRs) to CRD were quantified electromyographically before and after imipramine administration at 5, 15, 30, 60, 90 and 120 min. In the antagonist groups, the agents were administered 10 min before imipramine. The administration of imipramine (5-40 mg/kg) produced a dose-dependent reduction in VMR. The administration of yohimbine (a nonselective α₂-adrenoceptor antagonist, 1 mg/kg), BRL-44408 (an α(2A)-adrenoceptor antagonist, 1 mg/kg) or MK-912 (an α2C-adrenoceptor antagonist, 300 μg/kg) but not imiloxan (an α(2B)-adrenoceptor antagonist, 1 mg/kg) inhibited the antinociceptive effect of imipramine (20 mg/kg). Additionally, ketanserin (a 5-HT₂ receptor antagonist, 0.5, 1, and 2 mg/kg) and GR113808 (a 5-HT₄ receptor antagonist, 1 mg/kg) enhanced, and ondansetron (a 5-HT₃ receptor antagonist, 0.5, 1, and 2 mg/kg) failed to alter the imipramine-induced antinociceptive effect. Our data demonstrated that, in the CDR-induced rat visceral pain model, intravenous imipramine appeared to have antinociceptive potential and that α(2A)-/α(2C)-adrenoceptors and 5-HT₂/5-HT₄ receptors may be responsible for the antinociceptive effect of imipramine on visceral pain

  9. The glutamate transport inhibitor DL-Threo-β-Benzyloxyaspartic acid (DL-TBOA) differentially affects SN38- and oxaliplatin-induced death of drug-resistant colorectal cancer cells

    DEFF Research Database (Denmark)

    Cuesta, Elena Pedraz; Christensen, Sandra; Jensen, Anders A.;

    2015-01-01

    BACKGROUND: Colorectal cancer (CRC) is a leading cause of cancer death globally and new biomarkers and treatments are severely needed. METHODS: Here, we employed HCT116 and LoVo human CRC cells made resistant to either SN38 or oxaliplatin, to investigate whether altered expression of the high...... affinity glutamate transporters Solute Carrier (SLC)-1A1 and -1A3 (EAAT3, EAAT1) is associated with the resistant phenotypes. Analyses included real-time quantitative PCR, immunoblotting and immunofluorescence analyses, radioactive tracer flux measurements, and biochemical analyses of cell viability...... and glutamate transporter activity are altered in SN38-resistant CRC cells. Importantly, the non-selective glutamate transporter inhibitor DL-TBOA reduces chemotherapy-induced p53 induction and augments CRC cell death induced by SN38, while attenuating that induced by oxaliplatin. These findings may point...

  10. DHL‑TauZnNa, a newly synthesized α-lipoic acid derivative, induces autophagy in human colorectal cancer cells.

    Science.gov (United States)

    Hiratsuka, Takahiro; Inomata, Masafumi; Kono, Yohei; Yokoyama, Shigeo; Shiraishi, Norio; Kitano, Seigo

    2013-06-01

    In recent years, several antioxidant substances have been found to have an antiproliferative effect on various types of carcinomas. α-lipoic acid (ALA) induces apoptosis in several types of cancer cell lines, but it is difficult to apply α-lipoic acid in clinical use as it is easily oxidized and unstable. Recently, we succeeded in synthesizing the α-lipoic acid derivative sodium N-[6,8-dimercaptooctanoyl]-2-aminoethanesulfonate zinc complex (DHL-TauZnNa), which has highly stable antioxidant effects. We investigated whether DHL-TauZnNa elicits its antiproliferative effects in vivo and in vitro by inducing apoptosis, autophagy or cell cycle arrest, and we analyzed the expression of proteins related to these phenomena and their phosphorylation in HT-29 human colon cancer cells. Subcutaneously administered DHL-TauZnNa treatment applied daily for 41 days significantly inhibited tumor growth by 43% in a xenograft mouse model (P=0.0271). DHL-TauZnNa significantly reduced cell viability over that of controls in the trypan-blue exclusion test in a time- and dose-dependent manner (PDHL-TauZnNa increased the proportion of cells in S phase and decreased that of cells in G0/G1 phase in the cell cycle analysis of HT-29 cells. Although DHL-TauZnNa did not increase caspase-3/7 activity and DNA fragmentation in flow cytometry analysis, it increased the expression of microtubule-associated protein light chain 3-II. Autophagosomes and autolysosomes were observed by electron microscopy in the cytoplasm of HT-29 cells treated with DHL-TauZnNa. These results suggest that DHL-TauZnNa inhibited the proliferation of HT-29 cells through the mechanisms of G2/M cell cycle arrest and autophagy but not that of apoptosis. The newly synthesized ALA derivative DHL-TauZnNa may be expected to become a novel cancer therapeutic strategy through its induction of autophagy.

  11. Living as a Colorectal Cancer Survivor

    Science.gov (United States)

    ... Cancer Colorectal Cancer After Treatment Living as a Colorectal Cancer Survivor For many people with colorectal cancer, treatment ... cancer screening tests. Typical follow-up schedules after colorectal cancer Even if you have completed treatment, you will ...

  12. Multidisciplinary Design Optimization and Analysis of Hydrazine Monopropellant Propulsion System

    Directory of Open Access Journals (Sweden)

    Amirhossein Adami

    2015-01-01

    Full Text Available Monopropellant propulsion systems are widely used especially for low cost attitude control or orbit correction (orbit maintenance. To optimize the total propulsion system, subsystems should be optimized. Chemical decomposition, aerothermodynamics, and structure disciplines demand different optimum condition such as tank pressure, catalyst bed length and diameter, catalyst bed pressure, and nozzle geometry. Subsystem conflicts can be solved by multidisciplinary design optimization (MDO technique with simultaneous optimization of all subsystems with respect to any criteria and limitations. In this paper, monopropellant propulsion system design algorithm is presented and the results of the proposed algorithm are validated. Then, multidisciplinary design optimization of hydrazine propulsion system is proposed. The goal of optimization can be selected as minimizing the total mass (including propellant, minimizing the propellant mass (maximizing the Isp, or minimizing the dry mass. Minimum total mass, minimum propellant mass, and minimum dry mass are derived using MDO technique. It is shown that minimum total mass, minimum dry mass, and minimum propellant mass take place in different conditions. The optimum parameters include bed-loading, inlet pressure, mass flow, nozzle geometry, catalyst bed length and diameter, propellant tank mass, specific impulse (Isp, and feeding mass which are derived using genetic algorithm (GA.

  13. Potentiation of cardiovascular responses to hydralazine by diverse hydrazine derivatives.

    Science.gov (United States)

    Vidrio, H

    1994-10-01

    After the observation that in anesthetized rats the antitubercular agent isoniazid potentiates the hypotensive effect of the vasodilator hydralazine (H) and transforms the accompanying reflex tachycardia to bradycardia, a number of hydrazine (HYD) derivatives were tested for this interaction in pentobarbital-anesthetized rats. All HYDs studied elicited this response in varying degrees, isoniazid, thiosemicarbazide and thiocarbohydrazide being the most active. Experiments were then carried out to explore the possibility of an influence of the HYDs on reflex reactions to H due to interaction with pyridoxal, inhibition of glutamic acid decarboxylase and decreased levels of brain gamma-aminobutyric acid. Although the H-HYDs interaction was prevented by vagotomy, it was unaffected by exogenous pyridoxal, did not occur with the alpha adrenergic antagonist prazosin and was not mimicked by non-HYD pyridoxal reactors. In other experiments, pharmacokinetic interactions and monoamine oxidase inhibition were ruled out as alternative explanations for this phenomenon. It was concluded that the H-HYDs interaction is not related to a possible influence of these drugs on central gamma-aminobutyric acid cardiovascular regulation and that other presently unknown mechanisms are involved.

  14. SLCO1B1 and SLC19A1 gene variants and irinotecan-induced rapid response and survival: a prospective multicenter pharmacogenetics study of metastatic colorectal cancer.

    Directory of Open Access Journals (Sweden)

    Liu Huang

    Full Text Available BACKGROUND: Rapid response to chemotherapy in metastatic colorectal cancer (mCRC patients (response within 12 weeks of chemotherapy may increase the chance of complete resection and improved survival. Few molecular markers predict irinotecan-induced rapid response and survival. Single-nucleotide polymorphisms (SNPs in solute carrier genes are reported to correlate with the variable pharmacokinetics of irinotecan and folate in cancer patients. This study aims to evaluate the predictive role of 3 SNPs in mCRC patients treated with irinotecan and fluoropyrimidine-containing regimens. MATERIALS AND METHODS: Three SNPs were selected and genotyped in 137 mCRC patients from a Chinese prospective multicenter trial (NCT01282658. The chi-squared test, univariate and multivariable logistic regression model, and receiver operating characteristic analysis were used to evaluate correlations between the genotypes and rapid response. Kaplan-Meier survival analysis and Cox proportional hazard models were used to evaluate the associations between genotypes and survival outcomes. Benjamini and Hochberg False Discovery Rate correction was used in multiple testing. RESULTS: Genotype GA/AA of SNP rs2306283 of the gene SLCO1B1 and genotype GG of SNP rs1051266 of the gene SLC19A1 were associated with a higher rapid response rate (odds ratio [OR] =3.583 and 3.521, 95%CI =1.301-9.871 and 1.271-9.804, p=0.011 and p=0.013, respectively. The response rate was 70% in patients with both genotypes, compared with only 19.7% in the remaining patients (OR = 9.489, 95%CI = 2.191-41.093, Fisher's exact test p=0.002. Their significances were all maintained even after multiple testing (all p c < 0.05. The rs2306283 GA/AA genotype was also an independent prognostic factor of longer progression-free survival (PFS (hazard ratio = 0.402, 95%CI = 0.171-0.945, p=0.037. None of the SNPs predicted overall survival. CONCLUSIONS: Polymorphisms of solute carriers' may be useful to predict rapid

  15. Chemotherapy induced neutropenia at 1-month mark is a predictor of overall survival in patients receiving TAS-102 for refractory metastatic colorectal cancer: a cohort study.

    Science.gov (United States)

    Kasi, Pashtoon M; Kotani, Daisuke; Cecchini, Michael; Shitara, Kohei; Ohtsu, Atsushi; Ramanathan, Ramesh K; Hochster, Howard S; Grothey, Axel; Yoshino, Takayuki

    2016-07-13

    TAS-102 (trifluridine and tipiracil hydrochloride; a novel combination oral nucleoside anti-tumor agent) has recently received regulatory approval for patients with refractory metastatic colorectal cancer (mCRC). Internal review of data at a single-institution showed a trend towards better overall survival (OS) for patients who experienced chemotherapy-induced neutropenia at 1-month (CIN-1-month). To explore this finding further, a cohort study was designed based on outcome data from three centers in United States and one from Japan. CIN-1-month after starting TAS-102 was defined by the Common Terminology Criteria for Adverse Events (CTCAE), version 4.03 as a neutrophil count decrease of ≥ grade 2 (absolute neutrophil count < 1500/mm(3)). Patients had confirmed mCRC that was refractory to standard therapies. Patient demographics and clinical characteristics were compared between patients with CIN-1-month (CIN-1-month positive) versus those who did not have CIN-1-month (CIN-1-month negative); with the median progression-free survival (PFS) and OS were calculated using the Kaplan-Meier method, and differences evaluated using the Log-rank test. Our cohort study had a total of 149 patients with data regarding their neutrophil assessment at 1-month mark. Patients who developed ≥ grade 2 CIN-1-month had a both longer PFS (median 3.0 months versus 2.4 months; Log-rank P-value = 0.01), as well as OS (14.0 versus 5.6 months; Log-rank P-value < 0.0001). Only CIN-1-month (adjusted HR: 0.21 (95 % CI: 0.11-0.38) and higher baseline CEA levels (adjusted HR: 2.00 (95 % CI: 1.22-3.35) were noted to be independent predictors of OS. Furthermore, the CIN-1-month was noted to be a statistically significantly predictor of OS over a wide range of cutoffs. Our observations are novel and hypothesis generating. Neutropenia after starting TAS-102 was associated with better prognosis in patients with refractory mCRC. It can be postulated that the dosage of TAS

  16. 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...... 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...... procedures for colorectal cancer. Therefore, results of present research, validating RAE tests, are awaited with interest....

  17. Colorectal cancer screening.

    Science.gov (United States)

    Chan, Pak Wo Webber; Ngu, Jing Hieng; Poh, Zhongxian; Soetikno, Roy

    2017-01-01

    Colorectal cancer, which is the leading cancer in Singapore, can be prevented by increased use of screening and polypectomy. A range of screening strategies such as stool-based tests, flexible sigmoidoscopy, colonoscopy and computed tomography colonography are available, each with different strengths and limitations. Primary care physicians should discuss appropriate screening modalities with their patients, tailored to their individual needs. Physicians, patients and the government should work in partnership to improve uptake of colorectal cancer screening to reduce the morbidity and mortality from colorectal cancer. Copyright: © Singapore Medical Association.

  18. Oncogenic Ras, but not (V600E)B-RAF, protects from cholesterol depletion-induced apoptosis through the PI3K/AKT pathway in colorectal cancer cells.

    Science.gov (United States)

    Calleros, Laura; Sánchez-Hernández, Irene; Baquero, Pablo; Toro, María José; Chiloeches, Antonio

    2009-10-01

    Cholesterol is necessary for proliferation and survival of transformed cells. Here we analyse the effect of cholesterol depletion on apoptosis and the mechanisms underlying this effect in colorectal cancer cells carrying oncogenic Ras or (V600E)B-RAF mutations. We show that chronic cholesterol depletion achieved with lipoprotein-deficient serum (LPDS) and 25-hydroxycholesterol (25-HC) treatment results in a significant increase in apoptosis in HT-29 and Colo-205 cells containing the (V600E)B-RAF mutation, but not in HCT-116 and LoVo cells harbouring the (G13D)Ras mutation, or BE cells, which possess two mutations, (G13D)Ras and (G463V)B-RAF. We also demonstrate that oncogenic Ras protects from apoptosis induced by cholesterol depletion through constitutive activation of the phosphatidylinositol-3 kinase (PI3K)/AKT pathway. The specific activation of the PI3K/AKT pathway by overexpression of the (V12)RasC40 mutant or a constitutively active AKT decreases the LPDS plus 25-HC-induced apoptosis in HT-29 cells, whereas PI3K inhibition or abrogation of AKT expression renders HCT-116 sensitive to cholesterol depletion-induced apoptosis. Moreover, our data show that LPDS plus 25-HC increases the activity of c-Jun N-terminal kinase proteins only in HT-29 cells and that the inhibition of this kinase blocks the apoptosis induced by LPDS plus 25-HC. Finally, we demonstrate that AKT hyperactivation by oncogenic Ras protects from apoptosis, preventing the activation of c-Jun N-terminal kinase by cholesterol depletion. Thus, our data demonstrate that low levels of cholesterol induce apoptosis in colorectal cancer cells without oncogenic Ras mutations. These results reveal a novel molecular characteristic of colon tumours containing Ras or B-RAF mutations and should help in defining new targets for cancer therapy.

  19. Adjustable hydrazine modulation of single-wall carbon nanotube network field effect transistors from p-type to n-type

    Science.gov (United States)

    Dai, Ruixuan; Xie, Dan; Xu, Jianlong; Sun, Yilin; Sun, MengXing; Zhang, Cheng; Li, Xian

    2016-11-01

    Single-wall carbon nanotube (SWCNT) network field effect transistors (FETs), which show decent p-type electronic properties, have been fabricated. The use of hydrazine as an aqueous solution and a strong n-type dopant for the SWCNTs is demonstrated in this paper. The electrical properties are obviously tuned by hydrazine treatment at different concentrations on the surface of the SWCNT network FETs. The transport behavior of SWCNTs can be modulated from p-type to n-type, demonstrating the controllable and adjustable doping effect of hydrazine. With a higher concentration of hydrazine, more electrons can be transferred from the hydrazine molecules to the SWCNT network films, thus resulting in a change of threshold voltage, carrier mobility and on-current. By cleaning the device, the hydrazine doping effects vanish, which indicates that the doping effects of hydrazine are reversible. Through x-ray photoelectron spectroscopy (XPS) characterization, the doping effects of hydrazine have also been studied.

  20. Flow injection chemiluminescence determination of hydrazine by oxidation with chlorinated isocyanurates.

    Science.gov (United States)

    Safavi, Afsaneh; Karimi, Mohammad Ali

    2002-10-16

    A rapid and sensitive flow injection chemiluminescence (CL) method is described for the determination of hydrazine based on the CL generated during its reaction with either sodium dichloroisocyanurate (SDCC) or trichloroisocyanuric acid (TCCA) in alkaline medium. The emission intensity is greatly enhanced if dichlorofluorescein (DCF) as sensitizer is present in the reaction medium. The presence of citrate prevents the precipitation of some cations in the reaction medium and also causes an enhancement in emission intensity. The effect of analytical and flow injection variables on these CL systems and determination of hydrazine are discussed. The optimum parameters for the determination of hydrazine were studied and were found to be the following: SDCC and TCCA both 1x10(-3) M; NaOH, 2x10(-1) M; DCF, 5x10(-6) M; citrate, 1x10(-3) M and flow rate, 3.8 ml min(-1). The optimized method yielded 3sigma detection limits of 2x10(-7) and 3x10(-7) M for hydrazine with SDCC and TCCA oxidants, respectively. The method is simple, fast, sensitive, and precise and was applied to the determination of hydrazine in water samples.

  1. Preparation of fine nickel powders via reduction of nickel hydrazine complex precursors

    Institute of Scientific and Technical Information of China (English)

    HUANG Guo-yong; XU Sheng-ming; XU Gang; LI Lin-yan; ZHANG Li-feng

    2009-01-01

    Fine nickel(Ni) powders with controllable particle sizes were synthesized via the reduction of nickel hydrazine complex precursors of pure [Ni(N2H4)2]Cl2 and a mixture of [Ni(N2H4)2]Cl2 and [Ni(N2H4)3]Cl2 in aqueous solution. The mechanism of the formation of metallic Ni powders experiences the reduction of nickel hydroxide by hydrazine released from the ligand exchange reaction between nickel hydrazine complex and NaOH. In comparison with the method of preparing Ni powders from nickel salts, the method of making Ni powders via the reduction of nickel hydrazine complex precursors shows the advantages of using half dosage of hydrazine for complete reduction of nickel ions in solution, and the obtained Ni particles show less agglomeration and better dispersibility. Moreover, the average particle size of nickel powders can be controlled from 180 to 260 nm by adjusting the reaction molar ratio and concentration.

  2. 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...

  3. 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....

  4. Epidemiology of colorectal cancer

    Science.gov (United States)

    Marley, Andrew R; Nan, Hongmei

    2016-01-01

    Colorectal cancer is currently the third deadliest cancer in the United States and will claim an estimated 49,190 U.S. lives in 2016. The purpose of this review is to summarize our current understanding of this disease, based on nationally published statistics and information presented in peer-reviewed journal articles. Specifically, this review will cover the following topics: descriptive epidemiology (including time and disease trends both in the United States and abroad), risk factors (environmental, genetic, and gene-environment interactions), screening, prevention and control, and treatment. Landmark discoveries in colorectal cancer risk factor research will also be presented. Based on the information reviewed for this report, we suggest that future U.S. public health efforts aim to increase colorectal cancer screening among African American communities, and that future worldwide colorectal cancer epidemiology studies should focus on researching nutrient-gene interactions towards the goal of improving personalized treatment and prevention strategies.

  5. 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....

  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. Theoretical performance of liquid ammonia, hydrazine and mixture of liquid ammonia and hydrazine as fuels with liquid oxygen biflouride as oxidant for rocket engines : I-mixture of liquid ammonia and hydrazine

    Science.gov (United States)

    Huff, Vearl N; Gordon, Sanford

    1952-01-01

    Theoretical performance for mixture of 36.3 percent liquid ammonia and 63.7 percent hydrazine with liquid oxygen bifluoride as rocket propellant was calculated on assumption of equilibrium composition during expansion for a wide range of fuel-oxidant and expansios ratios. Parameters included were specific impulse, combustion-chamber temperature, nozzle exit temperature, composition mean molecular weight, characteristic velocity, coefficient of thrust and ratio of nozzle-exit area to throat area. For chamber pressure of 300 pounds per square inch absolute and expansion to 1 atmosphere, maximum specific impulse was 295.8 pound-seconds per pound. Five percent by weight of water in the hydrazine lowered specific impulse from about one to three units over a wide range of weight-percent fuel.

  8. Screening for colorectal cancer.

    Science.gov (United States)

    He, Jin; Efron, Jonathan E

    2011-01-01

    March is national colorectal cancer awareness month. It is estimated that as many as 60% of colorectal cancer deaths could be prevented if all men and women aged 50 years or older were screened routinely. In 2000, Katie Couric's televised colonoscopy led to a 20% increase in screening colonoscopies across America, a stunning rise called the "Katie Couric Effect". This event demonstrated how celebrity endorsement affects health behavior. Currently, discussion is ongoing about the optimal strategy for CRC screening, particularly the costs of screening colonoscopy. The current CRC screening guidelines are summarized in Table 2. Debates over the optimum CRC screening test continue in the face of evidence that 22 million Americans aged 50 to 75 years are not screened for CRC by any modality and 25,000 of those lives may have been saved if they had been screened for CRC. It is clear that improving screening rates and reducing disparities in underscreened communities and population subgroups could further reduce colorectal cancer morbidity and mortality. National Institutes of Health consensus identified the following priority areas to enhance the use and quality of colorectal cancer screening: Eliminate financial barriers to colorectal cancer screening and appropriate follow-up of positive results of colorectal cancer screening. Develop systems to ensure the high quality of colorectal cancer screening programs. Conduct studies to determine the comparative effectiveness of the various colorectal cancer screening methods in usual practice settings. Encouraging population adherence to screening tests and allowing patients to select the tests they prefer may do more good (as long as they choose something) than whatever procedure is chosen by the medical profession as the preferred test.

  9. Obesity and Colorectal Cancer

    OpenAIRE

    Gribovskaja-Rupp, Irena; Kosinski, Lauren; Ludwig, Kirk A.

    2011-01-01

    Obesity is a risk factor for colorectal cancer based on its molecular and metabolic effects on insulin and IGF-1, leptin, adipocytokines, and sex hormones. Obese men have a higher risk of colorectal cancer compared with normal weight men, but the association between obesity and rectal cancer is weaker than with colon cancer. There is a weaker association between obesity and colon cancer in women than in men, and no appreciable association between obesity and rectal cancer in women. Although o...

  10. Malignant colorectal polyps

    Institute of Scientific and Technical Information of China (English)

    Luis; Bujanda; Angel; Cosme; Ines; Gil; Juan; I; Arenas-Mirave

    2010-01-01

    Nowadays, the number of cases in which malignant colorectal polyps are removed is increasing due to colorectal cancer screening programmes. Cancerous polyps are classified into non-invasive high grade neoplasia (NHGN), when the cancer has not reached the muscularis mucosa, and malignant polyps, classed as T1, when they have invaded the submucosa. NHGN is considered cured with polypectomy, while the prognosis for malignant polyps depends on various morphological and histological factors. The prognostic facto...

  11. Techniques for colorectal anastomosis

    Institute of Scientific and Technical Information of China (English)

    Yik-Hong; Ho; Mohamed; Ahmed; Tawfi; k; Ashour

    2010-01-01

    Colorectal anastomotic leak remains one of the most feared post-operative complications, particularly after anterior resection of the rectum with, the shift from abdomino-peritoneal resections to total mesorectal excision and primary anastomosis. The literature fails to demonstrate superiority of stapled over hand-sewn techniques in colorectal anastomosis, regardless of the level of anastomosis, although a high stricture rate was noted in the former technique. Thus, improvements in safety aspects of anastom...

  12. Fibersol-2 induces apoptosis of Apc-deficient colorectal Cancer (SW480) cells and decreases polyp formation in Apc MIN mice.

    Science.gov (United States)

    Sancho, Sara Cuesta; Olson, Susan Losee; Young So, Eui; Shimomura, Kazuhiro; Ouchi, Toru; Preuss, Fabian

    2016-06-02

    The consumption of dietary fibers has been implicated with a lowered risk of human colorectal cancer. Proposed mechanisms involve alterations in the stool consistency, transit time, and formation of short-chain fatty acid by dietary fiber fermentation, and the reorganization of gut microbiota. Here we show that Fibersol-2, a digest-resistant maltodextrin, not only inhibits proliferation of colorectal SW480 cancer cell lines by increasing reactive oxygen species (ROS), but decreases the numbers of the adenoma count in Multiple Intestinal Neoplasia (MIN) mice carrying a mutation in the Adenomatous Polyposis Coli gene by 84 d of age. These observations provide direct evidence that Fibersol-2 intrinsically contains anti-cancer activity, independent of the intestinal metabolism and any potential interactions with the microbiota.

  13. [Epidemiology of colorectal cancer].

    Science.gov (United States)

    Bouvier, Anne-Marie; Launoy, Guy

    2015-06-01

    The incidence of colorectal cancer increased in France until the 2000s' then decreased. Time trends in incidence for this cancer varied according to its sublocation along the gut. Incidence increased for right and left colon cancers, whereas it remained stable for sigmoid cancers in males and decreased in females. Incidence decreased over time for rectal cancers. The proportion of colorectal cancer in the overall French cancer prevalence is 12%. In 2008, 121,000 patients had a colorectal cancer diagnosed in the 5 previous years. The cumulative risk of colorectal cancer increased from 3.9% for males born around 1900 to 4.9% for those born around 1930 and then slightly decreased, being 4.5% among those born around 1950. It remained at the same level for females and was 2.9% for those born around 1950. The prognosis of colorectal cancer improved over time. Net 5-year survival increased in males from 53% for cancers diagnosed between 1989 and 1991 to 58% for those diagnosed between 2001 and 2004. The highest improvement of 10 year survival rates concerned left colon and rectosigmoid junction (+19% in a decade). The progressive set up of national colorectal screening since the early 2000's and the introduction of recent immunological tests in 2015 should decrease the mortality for this cancer and, at term, should decrease its incidence too.

  14. Adiponectin and colorectal cancer.

    Science.gov (United States)

    Otani, Kensuke; Ishihara, Soichiro; Yamaguchi, Hironori; Murono, Koji; Yasuda, Koji; Nishikawa, Takeshi; Tanaka, Toshiaki; Kiyomatsu, Tomomichi; Hata, Keisuke; Kawai, Kazushige; Nozawa, Hiroaki; Watanabe, Toshiaki

    2017-02-01

    Colorectal cancer is an obesity-related malignancy. Adiponectin is an adipokine produced exclusively by adipose tissue, and its concentration in the serum is reduced in obesity. A low serum level of adiponectin is associated with an increased risk of various types of malignancies including colorectal cancer. These facts suggest that the epidemiological link between obesity and cancer may have a significant association with adiponectin. Although numerous studies of colorectal cancer have been reported, the results are conflicting about the anti-cancer effect of adiponectin, and how adiponectin affects carcinogenesis or cancer development remains controversial. Because adiponectin has multiple systemic effects and exists as a high serum concentration protein, the main role of adiponectin should be regulation of homeostasis, and it would not likely act as an anti-cancerous hormone. However, as epidemiological evidence shows, a low adiponectin level may be a basic risk factor for colorectal cancer. We speculate that when the colonic epithelium is stimulated or damaged by another carcinogen under the condition of a low adiponectin level, carcinogenesis is promoted and cancer development is facilitated. In this report, we summarize recent findings of the correlation between adiponectin and colorectal cancer and investigate the effect of adiponectin on colorectal cancer.

  15. Formulation & Storage Studies on Hydrazine-Based Gelled Propellants.

    Directory of Open Access Journals (Sweden)

    Mohan Verma

    1996-12-01

    Full Text Available The current trend in the area of high energy storable liquid rocket propellant research is to develop gelled/metallized systems and to explore the feasibility of their application in rocket motors. The idea stems from the fact that the conversion of a conventional liquid propellant to a gelled state and its subsequent metallization has the potential to significantly enhance the performance and density specific impulse. However, it is mandatory that the gelation of the liquid propellant be brought about with a minimum concentration of gellant and the gel formed should show a shear-thinning behaviour and good storage life. Keeping this in view, an experimental program to prepare thixotropic gels of hydrazine and its methyl substitutedderivatives like monomethyl hydrazineand unsymmetrical dimethyl hydrazinewas conducted under ambient conditions. The gellants investigated included particulate, chemical and synthetic materials. The gelation of the liquid fuels ..ould be brought about with gellant concentration as low as I wt per cent in some cases. Metallized gels using up to 40 wt per cent of AlIMg metal powders could be formulated. These heterogeneous systems showed a reduction in critical gellant concentration with degree of metallization. Further, less gelation time is observed if the gellant concentration is kept fixed and metal content is increased. The storage studies on gelled systems conducted over a period of three months showed good stability. The metallized systems, however, showed the settling of metal powders in meagre concentration which does not pose a major problem as these gels could be re-homogenized with stirring.

  16. Arrays of TiO2 Nanowires as Photoelectrochemical Sensors for Hydrazine Detection

    Directory of Open Access Journals (Sweden)

    Michael Ongaro

    2015-05-01

    Full Text Available Electrodes based on arrays of TiO2 nanowires were prepared by template sol-gel synthesis with the goal of developing a hydrazine photoelectrochemical sensor. Experimental conditions were chosen so that the gelation reaction occurred inside the nanopores of track-etched polycarbonate membranes, with consequent filling with TiO2 nanowires. Different procedures for the removal of the template were examined, in order to obtain arrays of self-standing TiO2 nanowires. The nanowire arrays were bound to fluorine doped tin oxide substrates to produce handy photoelectrodes. The photocurrent recorded with the photoelectrodes in the presence of hydrazine showed significant dependence on the pollutant concentration. The development of a photoelectrochemical sensor for hydrazine detection in water samples, based on this principle, is presented.

  17. Efficient hydrogen evolution in transition metal dichalcogenides via a simple one-step hydrazine reaction

    Science.gov (United States)

    Cummins, Dustin R.; Martinez, Ulises; Sherehiy, Andriy; Kappera, Rajesh; Martinez-Garcia, Alejandro; Schulze, Roland K.; Jasinski, Jacek; Zhang, Jing; Gupta, Ram K.; Lou, Jun; Chhowalla, Manish; Sumanasekera, Gamini; Mohite, Aditya D.; Sunkara, Mahendra K.; Gupta, Gautam

    2016-01-01

    Hydrogen evolution reaction is catalysed efficiently with precious metals, such as platinum; however, transition metal dichalcogenides have recently emerged as a promising class of materials for electrocatalysis, but these materials still have low activity and durability when compared with precious metals. Here we report a simple one-step scalable approach, where MoOx/MoS2 core-shell nanowires and molybdenum disulfide sheets are exposed to dilute aqueous hydrazine at room temperature, which results in marked improvement in electrocatalytic performance. The nanowires exhibit ∼100 mV improvement in overpotential following exposure to dilute hydrazine, while also showing a 10-fold increase in current density and a significant change in Tafel slope. In situ electrical, gate-dependent measurements and spectroscopic investigations reveal that hydrazine acts as an electron dopant in molybdenum disulfide, increasing its conductivity, while also reducing the MoOx core in the core-shell nanowires, which leads to improved electrocatalytic performance. PMID:27282871

  18. Surface-catalyzed air oxidation reactions of hydrazines: Tubular reactor studies

    Science.gov (United States)

    Kilduff, Jan E.; Davis, Dennis D.; Koontz, Steven L.

    1988-01-01

    The surface-catalyzed air oxidation reactions of hydrazine, monomethylhydrazine, unsymmetrical dimethylhydrazine, symmetrical dimethylhydrazine, trimethylhydrazine and tetramethylhydrazine were investigated in a metal-powder packed turbular flow reactor at 55 plus or minus 3 C. Hydrazine was completely reacted on all surfaces studied. The major products of monomethylhydrazine (MMH) oxidation were methanol, methane and methyldiazene. The di-, tri- and tetra-methyl hydrazines were essentially unreactive under these conditions. The relative catalytic reactivities toward MMH are: Fe greater than Al2O3 greater than Ti greater than Zn greater than 316 SS greater than Cr greater than Ni greater than Al greater than 304L SS. A kinetic scheme and mechanism involving adsorption, oxidative dehydrogenation and reductive elimination reactions on a metal oxide surface are proposed.

  19. Electroless plating of Ni-B film as a binder-free highly efficient electrocatalyst for hydrazine oxidation

    Science.gov (United States)

    Wen, Xiao-Ping; Dai, Hong-Bin; Wu, Lin-Song; Wang, Ping

    2017-07-01

    Hydrazine is a promising energy carrier for fuel cells owing to its combined advantages of high theoretical cell voltage, high-power density, and no greenhouse gas emission. By using an electroless plating process, we have prepared a robust Ni-B film grown on Ni foam that is highly effective for hydrazine electrooxidation in alkaline media. The effects of reaction temperature, concentrations of hydrous hydrazine and sodium hydroxide in the fuel solution on performance of hydrazine electrooxidation reaction are investigated. The mechanistic reason for the property advantage of as-prepared Ni-B/Ni foam catalyst over the relevant catalysts is discussed based on careful kinetics studies and characterization. The facile synthesis of Ni-based catalyst with high activity and good stability is of clear significance for the development of hydrous hydrazine as a viable energy carrier.

  20. Concentric-Electrode Organic Electrochemical Transistors: Case Study for Selective Hydrazine Sensing

    Directory of Open Access Journals (Sweden)

    Sébastien Pecqueur

    2017-03-01

    Full Text Available We report on hydrazine-sensing organic electrochemical transistors (OECTs with a design consisting of concentric annular electrodes. The design engineering of these OECTs was motivated by the great potential of using OECT sensing arrays in fields such as bioelectronics. In this work, poly(3,4-ethylenedioxythiophene:poly(styrenesulfonate (PEDOT:PSS-based OECTs have been studied as aqueous sensors that are specifically sensitive to the lethal hydrazine molecule. These amperometric sensors have many relevant features for the development of hydrazine sensors, such as a sensitivity down to 10−5 M of hydrazine in water, an order of magnitude higher selectivity for hydrazine than for nine other water-soluble common analytes, the capability to entirely recover its base signal after water flushing, and a very low operation voltage. The specificity for hydrazine to be sensed by our OECTs is caused by its catalytic oxidation at the gate electrode, and enables an increase in the output current modulation of the devices. This has permitted the device-geometry study of the whole series of 80 micrometric OECT devices with sub-20-nm PEDOT:PSS layers, channel lengths down to 1 µm, and a specific device geometry of coplanar and concentric electrodes. The numerous geometries unravel new aspects of the OECT mechanisms governing the electrochemical sensing behaviours of the device—more particularly the effect of the contacts which are inherent at the micro-scale. By lowering the device cross-talk, micrometric gate-integrated radial OECTs shall contribute to the diminishing of the readout invasiveness and therefore further promote the development of OECT biosensors.

  1. Concentric-Electrode Organic Electrochemical Transistors: Case Study for Selective Hydrazine Sensing

    Science.gov (United States)

    Pecqueur, Sébastien; Lenfant, Stéphane; Guérin, David; Alibart, Fabien; Vuillaume, Dominique

    2017-01-01

    We report on hydrazine-sensing organic electrochemical transistors (OECTs) with a design consisting of concentric annular electrodes. The design engineering of these OECTs was motivated by the great potential of using OECT sensing arrays in fields such as bioelectronics. In this work, poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS)-based OECTs have been studied as aqueous sensors that are specifically sensitive to the lethal hydrazine molecule. These amperometric sensors have many relevant features for the development of hydrazine sensors, such as a sensitivity down to 10−5 M of hydrazine in water, an order of magnitude higher selectivity for hydrazine than for nine other water-soluble common analytes, the capability to entirely recover its base signal after water flushing, and a very low operation voltage. The specificity for hydrazine to be sensed by our OECTs is caused by its catalytic oxidation at the gate electrode, and enables an increase in the output current modulation of the devices. This has permitted the device-geometry study of the whole series of 80 micrometric OECT devices with sub-20-nm PEDOT:PSS layers, channel lengths down to 1 µm, and a specific device geometry of coplanar and concentric electrodes. The numerous geometries unravel new aspects of the OECT mechanisms governing the electrochemical sensing behaviours of the device—more particularly the effect of the contacts which are inherent at the micro-scale. By lowering the device cross-talk, micrometric gate-integrated radial OECTs shall contribute to the diminishing of the readout invasiveness and therefore further promote the development of OECT biosensors. PMID:28287475

  2. Colorectal Cancer Risk Assessment Tool

    Science.gov (United States)

    ... 11/12/2014 Risk Calculator About the Tool Colorectal Cancer Risk Factors Download SAS and Gauss Code Page ... Rectal Cancer: Prevention, Genetics, Causes Tests to Detect Colorectal Cancer and Polyps Cancer Risk Prediction Resources Update November ...

  3. 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 ...

  4. Colorectal Cancer: Symptoms, Diagnosis, Treatment

    Science.gov (United States)

    ... Past Issues Special Section: Colorectal Cancer Colorectal Cancer: Symptoms, Diagnosis and Treatment Past Issues / Spring 2009 Table of ... version of this page please turn Javascript on. Symptoms Check with your healthcare provider if you have ...

  5. Synthesis, characterization and antioxidant study of N,N’-bis(2-chlorobenzamidothiocarbonyl)hydrazine

    Energy Technology Data Exchange (ETDEWEB)

    Firdausiah, Syadza; Hasbullah, Siti Aishah; Yamin, Bohari M. [School of Chemical Science and Food Technology, Faculty of Science and Technology, Universiti Kebangsaan Malaysia, 43600 Bangi, Selangor (Malaysia)

    2015-09-25

    N,N’-bis(2-chlorobenzamidothiocarbonyl)hydrazine was synthesized from 2-chlorobenzoylisothiocyanate and hydrazine in acetone. The compound was characterized by infrared, {sup 1}H and {sup 13}C NMR, and UV-Vis spectroscopies. X-ray crystallography study showed the molecule adopt trans configuration at both N-N and C-N bonds. The compound showed high antioxidant activity, EC{sub 50} of 374.89 µM, compared to ascorbic acid (EC{sub 50} of 561.36 µM)

  6. Selective fluorescent detection of aspartic acid and glutamic acid employing dansyl hydrazine dextran conjugate.

    Science.gov (United States)

    Nasomphan, Weerachai; Tangboriboonrat, Pramuan; Tanapongpipat, Sutipa; Smanmoo, Srung

    2014-01-01

    Highly water soluble polymer (DD) was prepared and evaluated for its fluorescence response towards various amino acids. The polymer consists of dansyl hydrazine unit conjugated into dextran template. The conjugation enhances higher water solubility of dansyl hydrazine moiety. Of screened amino acids, DD exhibited selective fluorescence quenching in the presence of aspartic acid (Asp) and glutamic acid (Glu). A plot of fluorescence intensity change of DD against the concentration of corresponding amino acids gave a good linear relationship in the range of 1 × 10(-4) M to 25 × 10(-3) M. This establishes DD as a potential polymeric sensor for selective sensing of Asp and Glu.

  7. Kinetic Study of Np(Ⅵ) Reduction With Tert-butyl Hydrazine

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Tert-butyl hydrazine(TBH) is a new salt free reductant, it can effectively reduce Np(Ⅵ) to Np(Ⅴ) but reduce Pu(Ⅳ)very slowly. Further more, it has the highest ratio of rate constant for Np(Ⅵ) reduction to the rate constant for Pu(Ⅳ) reduction in hydrazine derivatives, so it’s a promising reductant to separate Np, Pu effectively,Reduction kinetic study of the reaction in nitric acid is performed by spectrophotometry. The effect of some factors such as concentration of TBH, HNO3, Np(Ⅵ) and temperature on the redox

  8. The effect of hydrazine intercalation on the structure and capacitance of 2D titanium carbide (MXene).

    Science.gov (United States)

    Mashtalir, O; Lukatskaya, M R; Kolesnikov, A I; Raymundo-Piñero, E; Naguib, M; Barsoum, M W; Gogotsi, Y

    2016-04-28

    Herein we show that hydrazine intercalation into 2D titanium carbide (Ti3C2-based MXene) results in changes in its surface chemistry by decreasing the amounts of fluorine, OH surface groups and intercalated water. It also creates a pillaring effect between Ti3C2Tx layers pre-opening the structure and improving the accessability to active sites. The hydrazine treated material has demonstrated a greatly improved capacitance of 250 F g(-1) in acidic electrolytes with an excellent cycling ability for electrodes as thick as 75 μm.

  9. 结肠腺瘤性息肉病基因蛋白在二甲肼诱导大鼠大肠癌过程中的表达%Study on Expression of APC Protein in Rat Colorectal Carcinoma Induced by 1, 2 - Dimethylhydrazine

    Institute of Scientific and Technical Information of China (English)

    马晓强; 王伟杰; 李海

    2014-01-01

    Objective To observe the eXpression of APC protein in the formation process of colorectal carcinoma induced by 1, 2 -dimethylhydrazine to provide the new thought for its targeted therapy and early diagnosis. Methods SiXty male Sprague Dawley rats were randomly divided into the control group and the model group. The eXpression of APC protein in the intestinal mucosal tissue in 20 cases of colorectal cancer, 20 cases of colorectal adenoma and 20 cases of normal control was eXamined by the streptavidin - peroXidase (SP) immunohistochemistry. Results The immunohistochemical detection results displayed that the APC protein showed the strongly positive eXpression in normal colorectal mucosa tissue and had no eXpression in colorectal adenoma tissue and colorectal cancer tissue;the Western - blot assay results displayed that the specific band with a relative molecular weight of about 300 × 103 was seen in the normal colorectal tissue, but colorectal adenoma and colorectal cancer had no this band. Conclusion APC protein shows the non - eX-pression status in colorectal adenoma and colorectal carcinoma tissues, but is strongly eXpressed in the normal colorectal mucosal tissue, which suggesting that APC protein may be closely related with the occurrence and development process of colorectal cancer and is eX-pected to become the tumor marker of colorectal cancer.%目的:观察结肠腺瘤性息肉病基因(APC)蛋白在二甲肼诱导大鼠大肠癌形成过程中的表达,为大肠癌的靶向治疗和早期诊断提供新思路。方法将雄性 SD 大鼠60只随机分为正常对照组和模型组,应用免疫印迹法和免疫组织化学 SP 法,检测20例大肠癌组、20例大肠腺瘤组及20例正常对照组大鼠大肠黏膜组织中 APC 蛋白的表达情况。结果免疫组织化学检测结果显示,APC 蛋白在正常对照组大鼠大肠黏膜组织中均呈强阳性表达,在大肠腺瘤和大肠癌组大鼠大肠组织中未见表达;免

  10. Transformation of Hydrazine Fuels in Soil%肼类燃料在土壤中迁移转化

    Institute of Scientific and Technical Information of China (English)

    任向红

    2001-01-01

    Adsorption, degradation, transformation of hydrazines, methyl hydrazines and unsymmetrical dimethyl hydrazines in soil and their toxicity to microorganisms in soil are evaluated in the present investigation. It may be concluded that principal reactions between the hydrazine fuels and clay are physical absorption and chemical degradation. It has also been found that ion- exchange can only occur at low pH level, the unsolvable hydroxides may be formed on surface of the soil, suggesting that those could combine lots of hydrazine fuels by hydrogen- bond and ionization at the high pH level. The order of toxicity of the hydrazine fuels to microorganisms is hydrazines>methyl hydrazines> unsymmetrical dimethyl hydrazines. It has been indicated that some microorganisms in the soil can degrade the hydrazine fuels.%论述了对肼、甲基肼和偏二甲肼在土壤环境中的吸附、降解、迁移转化模型及对土壤中的微生物的毒性。肼类燃料在土壤环境中与粘土的作用最强,主要存在着物理吸附与化学降解两个方面。pH值较低时,在粘土中主要是可逆离子交换;pH值较高时,在土壤表面形成不溶的氢氧化物,通过氢键和离子作用结合大量肼类燃料。肼类燃料对土壤中的微生物的毒性大小是肼>甲基肼>偏二甲肼,土壤中的某些微生物也可促进肼类燃料的降解。

  11. Laparoscopic reintervention in colorectal surgery.

    NARCIS (Netherlands)

    Broek, RP Ten; Goor, H. van

    2008-01-01

    Laparoscopic colorectal surgery has developed in the 1990's and beginning of 2000. The favourable results and great progress in the development of laparoscopic techniques have expanded the indications of laparoscopic colorectal surgery. More and more complicated colorectal cases are treated laparosc

  12. 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 w...... 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.......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...

  13. Immunotherapy and immunoescape in colorectal cancer

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Immunotherapy encompasses a variety of interventions and techniques with the common goal of eliciting tumor cell destructive immune responses. Colorectal carcinoma often presents as metastatic disease that impedes curative surgery. Novel strategies such as active immunization with dendritic cells (DCs), gene transfer of cytokines into tumor cells or administration of immunostimulatory monoclonal antibodies (such as anti-CD137 or anti-CTLA-4) have been assessed in preclinical studies and are at an early clinical development stage. Importantly, there is accumulating evidence that chemotherapy and immunotherapy can be combined in the treatment of some cases with colorectal cancer, with synergistic potentiation as a result of antigens cross-presented by dendritic cells and/or elimination of competitor or suppressive T lymphocyte populations (regulatory T-cells). However, genetic and epigenetic unstable carcinoma cells frequently evolve mechanisms of immunoevasion that are the result of either loss of antigen presentation, or an active expression of immunosuppressive substances. Some of these actively immunosuppressive mechanisms are inducible by cytokines that signify the arrival of an effector immune response. For example, induction of 2, 3 indoleamine dioxygenase (IDO) by IFNy in colorectal carcinoma cells. Combinational and balanced strategies fostering antigen presentation, T-cell costimulation and interference with immune regulatory mechanisms will probably take the stage in translational research in the treatment of colorectal carcinoma.

  14. 5-Fluorouracil Induce the Expression of TLR4 on HCT116 Colorectal Cancer Cell Line Expressing Different Variants of TLR4

    OpenAIRE

    Davoodi, Homa; Hashemi, Seyed Reza; Seow, Heng Fong

    2013-01-01

    Two common single nucleotide polymorphisms (SNPs) of the human TLR4 gene, namely Asp299Gly (D299G) and Thr399Ile (T399I), have been shown to impair the ability of certain individuals to respond properly to TLR4 ligands. 5-Fluorouracil (5-FU) is widely used for the treatment of patients with advanced colon cancers. The present study examined the impact of two common polymorphisms of the TLR4 genes on the response of the HCT116 colorectal cancer cells to 5-FU. HCT116 was transfected with Flag-C...

  15. A Hydrazine-Free Wolff-Kishner Reaction Suitable for an Undergraduate Laboratory

    Science.gov (United States)

    Cranwell, Philippa B.; Russell, Andrew T.

    2016-01-01

    A Wolff-Kishner reaction that does not require hydrazine has been developed. The reaction sequence has two steps: formation of a carbomethoxyhydrazone from methyl hydrazinocarboxylate and acetophenone, then decomposition of this intermediate by treatment with potassium hydroxide in triethylene glycol. Purification is by filtration through a plug…

  16. Hydrazine Blending and Storage Facility Wastewater Treatment and Decommissioning Assessment. Version 3.1

    Science.gov (United States)

    1988-06-01

    concrete pads and dikes; a drum storage I 6764a 1-5 05 -- iti kwij 1-6a pad; a storage shed; a tool shed; an office shed, and associated Ipiping . Two... Oceanic and Atnospheric Administration). 1983. Local climatological data, Denver, CO. Neumann, E.J., and B. Jody. 1986. Neutralization of hydrazine

  17. X-ray absorption spectroscopy study on the thermal and hydrazine reduction of graphene oxide

    Energy Technology Data Exchange (ETDEWEB)

    Liang, Xianqing, E-mail: lxq@gxu.edu.cn [The Colleague of Physics Science and Technology, Guangxi University, Nanning 530004 (China); Wang, Yu [National Synchrotron Radiation Laboratory, University of Science and Technology of China, Hefei 230029 (China); Shanghai Institute of Applied Physics, Chinese Academy of Sciences, Shanghai 201204 (China); Zheng, Huiyuan [The Colleague of Physics Science and Technology, Guangxi University, Nanning 530004 (China); Wu, Ziyu, E-mail: wuzy@ustc.edu.cn [National Synchrotron Radiation Laboratory, University of Science and Technology of China, Hefei 230029 (China)

    2014-10-15

    Highlights: • XAS study of GO and reduced GO was performed. • Detailed evolution of the electronic structures and chemical bonding of GO was revealed. • A new efficient route for the reduction of GO is proposed. - Abstract: X-ray absorption spectroscopy (XAS) was applied to systemically investigate the deoxygenation of graphene oxide (GO) via annealing and hydrazine treatment. Detailed evolution of the electronic structures and chemical bonding of GO was presented. The enhanced intensity of π{sup *} resonance and the appearance of splitting σ{sup *} resonance in C K-edge XAS spectra suggest high extents of recoveries of π-conjugation upon reduction using thermal annealing or hydrazine. Experimental results revealed that the carboxyl as well as epoxide and hydroxyl groups on the surface of GO were thermally reduced first, followed by the more difficult removal of carbonyl and cyclic ether groups at higher temperatures. The hydrazine reduction could remove epoxide, hydroxyl and carboxyl groups effectively, whereas the carbonyl groups were partially reduced with the incorporation of nitrogen species simultaneously. The residual oxygen functional groups on hydrazine-reduced GO could be further removed after modest thermal annealing. It was proposed that a combination of both types of reductions would give the best deoxygenation efficiency for the production of graphene.

  18. Kinetic Study of the Reaction between Tert-butyl Hydrazine and Nitrous Acid

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    The kinetic study of the reaction between tert-butyl hydrazine(TBH)and nitrous acid in nitric acid system is performed by spectrophotometry. The effect of some factors such as the concentration of TBH, the concentration of nitric acid, ionic strength, temperature and the

  19. The effect of hydrazine intercalation on the structure and capacitance of 2D titanium carbide (MXene)

    Science.gov (United States)

    Mashtalir, O.; Lukatskaya, M. R.; Kolesnikov, A. I.; Raymundo-Piñero, E.; Naguib, M.; Barsoum, M. W.; Gogotsi, Y.

    2016-04-01

    Herein we show that hydrazine intercalation into 2D titanium carbide (Ti3C2-based MXene) results in changes in its surface chemistry by decreasing the amounts of fluorine, OH surface groups and intercalated water. It also creates a pillaring effect between Ti3C2Tx layers pre-opening the structure and improving the accessability to active sites. The hydrazine treated material has demonstrated a greatly improved capacitance of 250 F g-1 in acidic electrolytes with an excellent cycling ability for electrodes as thick as 75 μm.Herein we show that hydrazine intercalation into 2D titanium carbide (Ti3C2-based MXene) results in changes in its surface chemistry by decreasing the amounts of fluorine, OH surface groups and intercalated water. It also creates a pillaring effect between Ti3C2Tx layers pre-opening the structure and improving the accessability to active sites. The hydrazine treated material has demonstrated a greatly improved capacitance of 250 F g-1 in acidic electrolytes with an excellent cycling ability for electrodes as thick as 75 μm. Electronic supplementary information (ESI) available: Characterization methods, additional XRD patterns (Fig. S1) and INS spectra (Fig. S2-S4). See DOI: 10.1039/c6nr01462c

  20. Redox conditions effect on flow accelerated corrosion: Influence of hydrazine and oxygen

    Energy Technology Data Exchange (ETDEWEB)

    Bouvier, O. de [EDF, R and D Div., Moret sur Loing (France); Bouchacourt, M. [EDF, Engineering and Service Div., Villeurbanne (France); Fruzzetti, K. [EPRI, Science and Technology Div., Palo Alto, CA (United States)

    2002-07-01

    Flow accelerated corrosion (FAC) of carbon steels has been studied world-wide for more than twenty years and is now fairly well understood. The influence of several parameters like water chemistry (i.e. pH and oxygen content), temperature, hydrodynamic or mass transfer conditions (i.e. flow velocity, geometry, steam quality..) and steel composition on the corrosion kinetics has been demonstrated both theoretically and experimentally. However, the effect of a reducing environment and variable redox conditions have not yet been fully explored. It's well known that a reducing environment is effective in increasing the resistance of steam generator tubing to intergranular attack / stress corrosion cracking (IGA/SCC) and pitting. In that way, secondary water chemistry specifications have been modified from low hydrazine to high hydrazine chemistry in the steam-water circuit. Nevertheless, increasing hydrazine levels up to 200 {mu}g/kg could have a detrimental effect by potentially enhancing the FAC process. Moreover, in order to have a complete understanding of the possible impact of the water chemistry environment it is also important to consider the impact of redox conditions during shutdowns (cold and/or hot shutdowns) and start up periods when aerated water injections are made to maintain a constant water level in the Steam Generators from the auxiliary feedwater circuit. Therefore, a common EDF and EPRI R and D effort has been recently carried out to study the effects of hydrazine and oxygen on FAC. The results are presented as follows. (authors)

  1. Hydrazine reduction of transition metal oxides - In situ characterization using X-ray photoelectron spectroscopy

    Science.gov (United States)

    Littrell, D. M.; Tatarchuk, B. J.

    1986-01-01

    The transition metal oxides (TMOs) V2O5, FeO3, Co3O4, NiO, CuO, and ZnO were exposed to hydrazine at various pressures. The metallic surfaces were surveyed by in situ X-ray photoelectron spectroscopy to determine the irrelative rate of reduction by hydrazine. The most easily reducible oxide, CuO, could be reduced to the metallic state at room temperature and 10 to the -6th torr. The reaction is first order with respect to CuO, with an activation energy of about 35 kJ/mol. Two types of adsorption were seen to occur at 295 K: (1) a reversible component in which the measured N:Cu ratio increased to 0.60 at hydrazine pressures up to 0.5 torr, and (2) an irreversible component, with a N:Cu ratio of 0.28, which could not be removed by extended vacuum pumping. The results of this study are useful for the identification of TMO's that can be used as solid neatallizers of hydrazine spills, and for the preparation of metal surfaces for electroplating and evaporative thin-film coating.

  2. Highly selective amperometric sensor for the trace level detection of hydrazine at bismuth nanoparticles decorated graphene nanosheets modified electrode.

    Science.gov (United States)

    Devasenathipathy, Rajkumar; Mani, Veerappan; Chen, Shen-Ming

    2014-06-01

    A highly selective amperometric sensor was developed for the trace level determination of hydrazine at bismuth nanoparticles (Bi) decorated graphene nanosheets (GR) composite film modified glassy carbon electrode (GCE). GR-Bi nanocomposite has been successfully prepared via simple and facile chemical reduction approach and its structure was characterized by various techniques. Surface morphological and X-ray diffraction studies revealed the formation and high loading of Bi nanoparticles on graphene sheets. GR-Bi nanocomposite modified GCE exhibited greatly enhanced electrocatalytic performance towards electro-oxidation of hydrazine in terms of decrease in overpotential and increase in oxidation peak current (Ip). The kinetic parameters such as electron transfer coefficient (α) and diffusion coefficient (Do) of the hydrazine oxidation were determined to be 0.70 and 2.65×10(-5) cm(2) s(-1), respectively. An amperometric sensor has been fabricated which detects trace level concentration of hydrazine. The sensor exhibited a wide linear range from 20 nM to 0.28 mM and a very low detection limit (LOD) of 5 nM. Remarkably, this is the lowest LOD achieved for the determination of hydrazine in neutral pH among other reported electrochemical hydrazine sensors. In addition, the sensor selectively detects hydrazine even in the presence of 1000 fold excess quantity of common interferrants. The practical feasibility of the sensor has been assessed in water and urine samples with good recoveries. Furthermore, the sensor exhibited appreciable stability, repeatability and reproducibility results.

  3. New Modified-Multiwall Carbon Nanotubes Paste Electrode for Electrocatalytic Oxidation and Determination of Hydrazine Using Square Wave Voltammetry

    Institute of Scientific and Technical Information of China (English)

    Ali A. ENSAF; Mahsa LOTFI; Hassan KARIMI-MALEH

    2012-01-01

    The application of p-aminophenol as a suitable mediator, as a sensitive and selective voltammetric sensor for the determination of hydrazine using square wave voltammetric method were described. The modified multiwall carbon nanotubes paste electrode exhibited a good electrocatalytic activity for the oxidation of hydrazine at pH = 7.0. The catalytic oxidation peak currents showed a linear dependence of the peaks current to the hydrazine concentrations in the range of 0.5–175 μmol/L with a correlation coefficient of 0.9975. The detection limit (S/N = 3) was estimated to be 0.3 μmol/L of hydrazine. The relative standard deviations for 0.7 and 5.0 μmol/L hydrazine were 1.7 and 1.1%, respectively. The modified electrode showed good sensitivity and selectivity. The diffusion coefficient (D = 9.5 × 10–4 cm2/s) and the kinetic parameters such as the electron transfer coefficient (α = 0.7) of hydrazine at the surface of the modified electrode were determined using electrochemical approaches. The electrode was successfully applied for the determination of hydrazine in real samples with satisfactory results.

  4. Cyclic voltammetry deposition of copper nanostructure on MWCNTs modified pencil graphite electrode: An ultra-sensitive hydrazine sensor.

    Science.gov (United States)

    Heydari, Hamid; Gholivand, Mohammad B; Abdolmaleki, Abbas

    2016-09-01

    In this study, Copper (Cu) nanostructures (CuNS) were electrochemically deposited on a film of multiwall carbon nanotubes (MWCNTs) modified pencil graphite electrode (MWCNTs/PGE) by cyclic voltammetry method to fabricate a CuNS-MWCNTs composite sensor (CuNS-MWCNT/PGE) for hydrazine detection. Scanning electron microscopy (SEM) and Energy-dispersive X-ray spectroscopy (EDX) were used for the characterization of CuNS on the MWCNTs matrix. The composite of CuNS-MWCNTs was characterized with cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS). The preliminary studies showed that the proposed sensor have a synergistic electrocatalytic activity for the oxidation of hydrazine in phosphate buffer. The catalytic currents of square wave voltammetry had a linear correlation with the hydrazine concentration in the range of 0.1 to 800μM with a low detection limit of 70nM. Moreover, the amperometric oxidation current exhibited a linear correlation with hydrazine concentration in the concentration range of 50-800μM with the detection limit of 4.3μM. The proposed electrode was used for the determination of hydrazine in real samples and the results were promising. Empirical results also indicated that the sensor had good reproducibility, long-term stability, and the response of the sensor to hydrazine was free from interferences. Moreover, the proposed sensor benefits from simple preparation, low cost, outstanding sensitivity, selectivity, and reproducibility for hydrazine determination. Copyright © 2016. Published by Elsevier B.V.

  5. Cyclic voltammetry deposition of copper nanostructure on MWCNTs modified pencil graphite electrode: An ultra-sensitive hydrazine sensor

    Energy Technology Data Exchange (ETDEWEB)

    Heydari, Hamid [Faculty of Sciences, Razi University, Kermanshah (Iran, Islamic Republic of); Gholivand, Mohammad B., E-mail: mbgholivand@razi.ac.ir [Faculty of Sciences, Razi University, Kermanshah (Iran, Islamic Republic of); Abdolmaleki, Abbas [Department of Chemistry, Malek Ashtar University of Technology, Tehran (Iran, Islamic Republic of)

    2016-09-01

    In this study, Copper (Cu) nanostructures (CuNS) were electrochemically deposited on a film of multiwall carbon nanotubes (MWCNTs) modified pencil graphite electrode (MWCNTs/PGE) by cyclic voltammetry method to fabricate a CuNS–MWCNTs composite sensor (CuNS–MWCNT/PGE) for hydrazine detection. Scanning electron microscopy (SEM) and Energy-dispersive X-ray spectroscopy (EDX) were used for the characterization of CuNS on the MWCNTs matrix. The composite of CuNS-MWCNTs was characterized with cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS). The preliminary studies showed that the proposed sensor have a synergistic electrocatalytic activity for the oxidation of hydrazine in phosphate buffer. The catalytic currents of square wave voltammetry had a linear correlation with the hydrazine concentration in the range of 0.1 to 800 μM with a low detection limit of 70 nM. Moreover, the amperometric oxidation current exhibited a linear correlation with hydrazine concentration in the concentration range of 50–800 μM with the detection limit of 4.3 μM. The proposed electrode was used for the determination of hydrazine in real samples and the results were promising. Empirical results also indicated that the sensor had good reproducibility, long-term stability, and the response of the sensor to hydrazine was free from interferences. Moreover, the proposed sensor benefits from simple preparation, low cost, outstanding sensitivity, selectivity, and reproducibility for hydrazine determination. - Highlights: • The Copper nanostructures (CuNS) were prepared by cyclic voltammetry deposition. • The CuNS-MWCNT/PGE sensor shows high activity toward hydrazine (N{sub 2}H{sub 4}). • The proposed sensor exhibits a wide linear range (0.1 to 800 μM), low detection limit (70 nM), high sensitivity and stability for hydrazine.

  6. Effect of hydrazine on general corrosion of carbon and low-alloyed steels in pressurized water reactor secondary side water

    Energy Technology Data Exchange (ETDEWEB)

    Järvimäki, Sari [Fortum Ltd, Loviisa Power Plant, Loviisa (Finland); Saario, Timo; Sipilä, Konsta [VTT Technical Research Centre of Finland Ltd., Nuclear Safety, P.O. Box 1000, FIN-02044 VTT (Finland); Bojinov, Martin, E-mail: martin@uctm.edu [Department of Physical Chemistry, University of Chemical Technology and Metallurgy, Kl. Ohridski Blvd, 8, 1756 Sofia (Bulgaria)

    2015-12-15

    Highlights: • The effect of hydrazine on the corrosion of steel in secondary side water investigated by in situ and ex situ techniques. • Oxide grown on steel in 100 ppb hydrazine shows weaker protective properties – higher corrosion rates. • Possible explanation of the accelerating effect of higher concentrations of hydrazine on flow assisted corrosion offered. - Abstract: The effect of hydrazine on corrosion rate of low-alloyed steel (LAS) and carbon steel (CS) was studied by in situ and ex situ techniques under pressurized water reactor secondary side water chemistry conditions at T = 228 °C and pH{sub RT} = 9.2 (adjusted by NH{sub 3}). It is found that hydrazine injection to a maximum level of 5.06 μmol l{sup −1} onto surfaces previously oxidized in ammonia does not affect the corrosion rate of LAS or CS. This is confirmed also by plant measurements at Loviisa NPP. On the other hand, hydrazine at the level of 3.1 μmol l{sup −1} decreases markedly the amount and the size of deposited oxide crystals on LAS and CS surface. In addition, the oxide grown in the presence of 3.1 μmol l{sup −1} hydrazine is somewhat less protective and sustains a higher corrosion rate compared to an oxide film grown without hydrazine. These observations could explain the accelerating effect of higher concentrations of hydrazine found in corrosion studies of LAS and CS.

  7. [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.

  8. Colorectal cancer screening

    Institute of Scientific and Technical Information of China (English)

    Ramona M McLoughlin; Colm A O'Morain

    2006-01-01

    Colorectal cancer is a major public health burden worldwide.There is clear-cut evidence that screening will reduce colorectal cancer mortality and the only contentious issue is which screening tool to use.Most evidence points towards screening with fecal occult blood testing.The immunochemical fecal occult blood tests have a higher sensitivity than the guaiac-based tests.In addition,their automation and haemoglobin quantification allows a threshold for colonoscopy to be selected that can be accommodated within individual health care systems.

  9. Brother of Regulator of Imprinted Sites (BORIS) suppresses apoptosis in colorectal cancer

    Science.gov (United States)

    Zhang, Yanmei; Fang, Mengdie; Song, Yongfei; Ren, Juan; Fang, Jianfei; Wang, Xiaoju

    2017-01-01

    Identifying oncogenes that promote cancer cell proliferation or survival is critical for treatment of colorectal cancer. The Brother of Regulator of Imprinted Sites (BORIS) is frequently expressed in most types of cancer, but rarely in normal tissues. Aberrantly expressed BORIS relates to colorectal cancer, but its function in colorectal cancer cells remains unclear. In addition, previous studies indicated the significance of cytoplasm-localized BORIS in cancer cells. However, none of them investigated its function. Herein, we investigated the functions of BORIS in cancer cell proliferation and apoptosis and the role of cytoplasm-localized BORIS in colorectal cancer. BORIS expression correlated with colorectal cancer proliferation. BORIS overexpression promoted colorectal cancer cell growth, whereas BORIS knockdown suppressed cell proliferation. Sensitivity of colorectal cancer cells to 5-fluorouracil (5-FU) was inversely correlated with BORIS expression. These data suggest that BORIS functions as an oncogene in colorectal cancer. BORIS silencing induced reactive oxygen species (ROS) production and apoptosis, whereas BORIS supplementation inhibited apoptosis induced by BORIS short interfering RNA (siRNA), hydrogen peroxide (H2O2) or 5-FU. Introduction of BORIS-ZFdel showed that cytoplasmic localization of BORIS inhibited apoptosis but not ROS production. Our study highlights the anti-apoptotic function of BORIS in colorectal cancer. PMID:28098226

  10. ABCB5 identifies a therapy-refractory tumor cell population in colorectal cancer patients

    Science.gov (United States)

    Wilson, Brian J.; Schatton, Tobias; Zhan, Qian; Gasser, Martin; Ma, Jie; Saab, Karim R.; Schanche, Robin; Waaga-Gasser, Ana-Maria; Gold, Jason S.; Huang, Qin; Murphy, George F.; Frank, Markus H.; Frank, Natasha Y.

    2012-01-01

    Identification and reversal of treatment resistance mechanisms of clinically refractory tumor cells is critical for successful cancer therapy. Here we show that ATP-binding cassette member B5 (ABCB5) identifies therapy-refractory tumor cells in colorectal cancer patients following fluorouracil (5-FU)-based chemoradiation therapy and provide evidence for a functional role of ABCB5 in colorectal cancer 5-FU resistance. Examination of human colon and colorectal cancer specimens revealed ABCB5 to be expressed only on rare cells within healthy intestinal tissue, whereas clinical colorectal cancers exhibited substantially increased levels of ABCB5 expression. Analysis of successive, patient-matched biopsy specimens obtained prior to and following neoadjuvant 5-FU-based chemoradiation therapy in a series of colorectal cancer patients revealed markedly enhanced abundance of ABCB5-positive tumor cells when residual disease was detected. Consistent with this finding, the ABCB5-expressing tumor cell population was also treatment-refractory and exhibited resistance to 5-FU-induced apoptosis in a colorectal cancer xenograft model of 5-FU monotherapy. Mechanistically, shRNA-mediated ABCB5 knockdown significantly inhibited tumorigenic xenograft growth and sensitized colorectal cancer cells to 5-FU-induced cell killing. Our results identify ABCB5 as a novel molecular marker of therapy-refractory tumor cells in colorectal cancer patients and point to a need for consistent eradication of ABCB5-positive resistant tumor cell populations for more effective colorectal cancer therapy. PMID:21652540

  11. Understanding CO2 capture mechanisms in aqueous hydrazine via combined NMR and first-principles studies.

    Science.gov (United States)

    Lee, Byeongno; Stowe, Haley M; Lee, Kyu Hyung; Hur, Nam Hwi; Hwang, Son-Jong; Paek, Eunsu; Hwang, Gyeong S

    2017-09-13

    Aqueous amines are currently the most promising solution for large-scale CO2 capture from industrial sources. However, molecular design and optimization of amine-based solvents have proceeded slowly due to a lack of understanding of the underlying reaction mechanisms. Unique and unexpected reaction mechanisms involved in CO2 absorption into aqueous hydrazine are identified using (1)H, (13)C, and (15)N NMR spectroscopy combined with first-principles quantum-mechanical simulations. We find production of both hydrazine mono-carbamate (NH2-NH-COO(-)) and hydrazine di-carbamate ((-)OOC-NH-NH-COO(-)), with the latter becoming more populated with increasing CO2 loading. Exchange NMR spectroscopy also demonstrates that the reaction products are in dynamic equilibrium under ambient conditions due to CO2 exchange between mono-carbamate and di-carbamate as well as fast proton transfer between un-protonated free hydrazine and mono-carbamate. The exchange rate rises steeply at high CO2 loadings, enhancing CO2 release, which appears to be a unique property of hydrazine in aqueous solution. The underlying mechanisms of these processes are further evaluated using quantum mechanical calculations. We also analyze and discuss reversible precipitation of carbamate and conversion of bicarbonate to carbamates. The comprehensive mechanistic study provides useful guidance for optimal design of amine-based solvents and processes to reduce the cost of carbon capture. Moreover, this work demonstrates the value of a combined experimental and computational approach for exploring the complex reaction dynamics of CO2 in aqueous amines.

  12. Morpho-functional Blood Changes Under the Influence of Hydrazine and Correction with “Salsokollin” Drug

    Directory of Open Access Journals (Sweden)

    Marat R. Khanturin

    2012-09-01

    Full Text Available Hydrazine derivatives are used in different areas: airspace industry, healthcare, laboratory-diagnostic activity, that’s why the environment is subjected to contamination by hydrazines. For Kazakhstan, which houses the "Baikonur" Cosmodrome, the problem of environmental pollution by rocket fuel and its components is a burning issue nowadays. This article deals with the impacts by industrial hydrazines on biochemical data of the blood and its correction with the “Salsokollin” Drug. The samples of bilirubin, the whole protein, urea, creatinine, cholesterol, glucose, aminotransferase a-amylases, α-amylase were taken. The thymol test was carried out.

  13. Correlation of reversion-inducing cysteine-rich protein with kazal motifs (RECK) and extracellular matrix metalloproteinase inducer (EMMPRIN), with MMP-2, MMP-9, and survival in colorectal cancer.

    NARCIS (Netherlands)

    Jagt, M. van der; Sweep, C.G.J.; Waas, E.T.; Hendriks, T.; Ruers, T.J.M.; Merry, A.H.; Wobbes, Th.; Span, P.N.

    2006-01-01

    mRNA, and latent and active levels MMP-2 and -9 were higher in tumor tissue compared to normal tissue from 63 patients with colorectal cancer, whereas RECK and EMMPRIN levels were lower. Correlations between mRNA, latent, and active MMP were particular high for MMP-2 in tumor tissue (R(s)=0.6-0.8, P

  14. Colorectal Cancer Rates by Race and Ethnicity

    Science.gov (United States)

    ... Associated Lung Ovarian Prostate Skin Uterine Cancer Home Colorectal Cancer Rates by Race and Ethnicity Language: English (US) ... Tweet Share Compartir The rate of people getting colorectal cancer or dying from colorectal cancer varies by race ...

  15. Anticancer activity of calyx of Diospyros kaki Thunb. through downregulation of cyclin D1 via inducing proteasomal degradation and transcriptional inhibition in human colorectal cancer cells.

    Science.gov (United States)

    Park, Su Bin; Park, Gwang Hun; Song, Hun Min; Son, Ho-Jun; Um, Yurry; Kim, Hyun-Seok; Jeong, Jin Boo

    2017-09-05

    Although it has been reported to contain high polyphenols, the pharmacological studies of the calyx of Diospyros kaki Thunb (DKC) have not been elucidated in detail. In this study, we elucidated anti-cancer activity and potential molecular mechanism of DKC against human colorectal cancer cells. Anti-cell proliferative effect of 70% ethanol extracts from the calyx of Diospyros kaki (DKC-E70) was evaluated by MTT assay. The effect of DKC-E70 on the expression of cyclin D1 in the protein and mRNA level was evaluated by Western blot and RT-PCR, respectively. DKC-E70 suppressed the proliferation of human colorectal cancer cell lines such as HCT116, SW480, LoVo and HT-29. Although DKC-E70 decreased cyclin D1 expression in protein and mRNA level, decreased level of cyclin D1 protein by DKC-E70 occurred at the earlier time than that of cyclin D1 mRNA, which indicates that DKC-E70-mediated downregulation of cyclin D1 protein may be a consequence of the induction of degradation and transcriptional inhibition of cyclin D1. In cyclin D1 degradation, we found that cyclin D1 downregulation by DKC-E70 was attenuated in presence of MG132. In addition, DKC-E70 phosphorylated threonine-286 (T286) of cyclin D1 and T286A abolished cyclin D1 downregulation by DKC-E70. We also observed that DKC-E70-mediated T286 phosphorylation and subsequent cyclin D1 degradation was blocked in presence of the inhibitors of ERK1/2, p38 or GSK3β. In cyclin D1 transcriptional inhibition, DKC-E70 inhibited the expression of β-catenin and TCF4, and β-catenin/TCF-dependent luciferase activity. Our results suggest that DKC-E70 may downregulate cyclin D1 as one of the potential anti-cancer targets through cyclin D1 degradation by T286 phosphorylation dependent on ERK1/2, p38 or GSK3β, and cyclin D1 transcriptional inhibition through Wnt signaling. From these findings, DKC-E70 has potential to be a candidate for the development of chemoprevention or therapeutic agents for human colorectal cancer.

  16. 高脂饮食促进结直肠癌发生机制的研究进展%Research Progress of the Mechanisms of High Fat Diet Induced Colorectal Cancer

    Institute of Scientific and Technical Information of China (English)

    陈雪; 曹海龙; 王斯南; 王邦茂

    2016-01-01

    Colorectal cancer (CRC) is one of the most common gastrointestinal tumors. It has been the third most frequently diagnosed cancer in China. Yet, the etiology of CRC is complex, including genetics and environmental factors, and the latter aspect is significantly as-sociated with the fast pace western life style. High fat diet increases the risk of CRC in many ways, including influencing bile acid metabo-lism, changing intestinal permeability, innate immunity and gut microbiota, as well as inducing low grade inflammation. In this article, we summarized the recent advances in the mechanisms of how high fat diet promotes CRC.%结直肠癌(colorectal cancer,CRC)是消化道常见肿瘤之一,在我国已成为发病率居第三位的恶性肿瘤。CRC病因复杂,主要包括遗传背景和环境因素,而后者与生活方式关系密切。高脂饮食通过影响胆汁酸代谢,改变肠道通透性、固有免疫及肠道菌群,进而诱发低度炎症等,增加了CRC的发病风险并促进了CRC的发生发展。本文就近年来对高脂饮食促进CRC的分子机制研究进行综述。

  17. Simultaneous determination of hydrazine and phenyl hydrazine using 4′-(4-carboxyphenyl)-2,2′:6′,2″ terpyridine diacetonitrile triphenylphosphine ruthenium(II) tetrafluoroborate complex functionalized multiwalled carbon nanotubes modified electrode

    Energy Technology Data Exchange (ETDEWEB)

    Tiwari, Ida, E-mail: idatiwari_2001@rediffmail.com [Department of Chemistry (Center of Advanced Study), Faculty of Science, Banaras Hindu University, Varanasi (India); Gupta, Mandakini; Sinha, Preeti [Department of Chemistry (Center of Advanced Study), Faculty of Science, Banaras Hindu University, Varanasi (India); Banks, Craig E. [Faculty of Science and Engineering, School of Science and the Environment, Division of Chemistry and Environmental Science, Manchester Metropolitan University, Chester Street, Manchester M1 5GD (United Kingdom)

    2014-12-15

    Highlights: • A nanocomposite of ruthenium(II) terpyridine, triphenylphosphine based complex and multiwalled carbon nanotubes have been used first time for simultaneous detection of hydrazine and phenyl hydrazine. • The detection limit reported is lower as compared to other reported works. • The paper also focuses towards effect of ligand variation attached to ruthenium(II) terpyridine based complexes complex for the hydrazine and phenyl hydrazine detection. • Nanocomposite does not involve any biological entity hence high stability. - Abstract: A nanocomposite based on the incorporation of the complex 4′-(4-carboxyphenyl)-2,2′:6′,2″ terpyridine triphenylphosphine diacetonitrile ruthenium(II) tetrafluoroborate with multiwalled carbon nanotubes and ionomer supported upon a glassy carbon electrode substrate is reported and characterized with scanning electron microscopy, transmission electron microscopy and infrared spectroscopy. The electrochemical behavior and stability of the composite electrode was investigated via cyclic voltammetry. The modified electrode exhibits an electro-catalytic activity towards the oxidation of both hydrazine and phenyl hydrazine in 0.1 M phosphate buffer solution (PBS, pH 7.4). The oxidation of hydrazine and phenyl hydrazine occurs at 0.81 V and 0.32 V with limit of detection found to be 3.7 × 10{sup −7} M and 1.15 × 10{sup −7} M and having a linear range from 5 × 10{sup −6} M to 6.5 × 10{sup −3} M, and 5 × 10{sup −6} M to 0.2 × 10{sup −3} M, respectively.

  18. Kinetic Study of the Electro-Catalytic Oxidation of Hydrazine on Cobalt Hydroxide Modified Glassy Carbon Electrode

    Institute of Scientific and Technical Information of China (English)

    HASANZADEH,Mohammad; KARIM-NEZHAD,Ghasem; SHADJOU,Nasrin; KHALILZADEH,Balal; SAGHATFOROUSH,Lotali; ERSHAD,Sohrab; KAZEMAN,Isa

    2009-01-01

    Electrocatalytic oxidation of hydrazine was investigated on a cobalt hydroxide modified glassy carbon (CHM-GC) electrode in alkaline solution.The process of oxidation involved and its kinetics were established by using cyclic voltammetry,chronoamperometry techniques as well as steady state polarization measurements.In cyclic voltammetry (CV) studies,in the presence of hydrazine the peak current increase of the oxidation of cobalt hydroxide is followed by a decrease in the corresponding cathodic current.This indicates that hydrazine is oxidized on the redox mediator that is immobilized on the electrode surface via an electrocatalytic mechanism.A mechanism based on the electrochemical generation of Co(IV) active sites and their subsequent consumption by the hydrazine in question was also investigated.

  19. Fever as the only manifestation of hypersensitivity reactions associated with oxaliplatin in a patient with colorectal cancer Oxaliplatin-induced hypersensitivity reaction

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Hypersensitivity reactions (HSR) to oxaliplatin in patients with colorectal cancer include facial flushing, erythema,pruritis, fever, tachycardia, dyspnea, tongue swelling,rash/hives, headache, chills, weakness, vomiting, burning sensations, dizziness, and edema. We report a patient with fever as the sole manifestation of initial HSR, review the literature and discuss the management of HSR. A 57-year-old female with T3N2M0 rectal adenocarcinoma received modified FOLFOX-6. She tolerated the first 8 cycles without any toxicities except grade 1 peripheral neuropathy and nausea. During 9th and 10th infusions,she developed fever to a maximum of 38.3℃ with stable hemodynamic status despite medications. During 11th infusion, she developed grade 3 HSR consisting of symptomatic bronchospasm, hypotension, nausea,vomiting, cough, and fever. On examination, she was pale, cyanotic, with a temperature of 38.8℃, BP dropped to 95/43 mm Hg, pulse of 116/min and O2 saturation of 88%-91%. She was hospitalized for management and recovered in 24 h. Fever alone is not a usual symptom of oxaliplatin HSR. It may be indicative that the patient may develop serious reactions subsequently, as did our patient who developed hypotension with the third challenge. Treatment and prevention consists of slowing the infusion rate, use of steroids and antagonists of Type 1 and 2 histamine receptor antagonists, whereas desensitization could help to provide the small number of patients who experience severe HSR with the ability to further receive an effective therapy for their colorectal cancer.

  20. Long-term cultivation of colorectal carcinoma cells with anti-cancer drugs induces drug resistance and telomere elongation: an in vitro study

    Directory of Open Access Journals (Sweden)

    Mochizuki Hidetaka

    2001-08-01

    Full Text Available Abstract Background The role of telomerase activation in the expression and/or maintenance of drug resistance is not clearly understood. Therefore, we investigated the relationships, among the telomerase activity, telomere length and the expression of multidrug resistance genes in colorectal cancer cell lines cultivated with anti-cancer drugs. Methods LoVo and DLD-1 cells were continuously grown in the presence of both CDDP and 5-FU for up to 100 days. Cell proliferation, telomerase activity, telomere length and the expression of multidrug resistance genes were serially monitored as the PDL increased. Results The expression of multidrug resistance genes tended to increase as the PDL increased. However, an abnormal aneuploid clone was not detected as far as the cells were monitored by a DNA histogram analysis. Tumor cells showing resistance to anti-cancer drugs revealed a higher cell proliferation rate. The telomere length gradually increased with a progressive PDL. The telomerase activity reached a maximum level at 15 PDL in LoVo cells and at 27 PDL in DLD-1 cells. An increase in the mRNA expression of the telomerase components, especially in hTERT and in hTR, was observed at the same PDLs. Conclusions These results suggest that a high telomerase activity and an elongation of telomeres both appear to help maintain and/or increase drug resistance in colorectal cancer cells. Cancer cells with long telomeres and a high proliferative activity may thus be able to better survive exposure to anti-cancer drugs. This is presumably due to an increased chromosome stability and a strong expression of both mdr-1 and MRP genes.

  1. Brain-derived neurotrophic factor (BDNF)-induced tropomyosin-related kinase B (Trk B) signaling is a potential therapeutic target for peritoneal carcinomatosis arising from colorectal cancer.

    Science.gov (United States)

    Tanaka, Koji; Okugawa, Yoshinaga; Toiyama, Yuji; Inoue, Yasuhiro; Saigusa, Susumu; Kawamura, Mikio; Araki, Toshimitsu; Uchida, Keiichi; Mohri, Yasuhiko; Kusunoki, Masato

    2014-01-01

    Tropomyosin-related receptor kinase B (TrkB) signaling, stimulated by brain-derived neurotrophic factor (BDNF) ligand, promotes tumor progression, and is related to the poor prognosis of various malignancies. We sought to examine the clinical relevance of BDNF/TrkB expression in colorectal cancer (CRC) tissues, its prognostic value for CRC patients, and its therapeutic potential in vitro and in vivo. Two hundred and twenty-three CRC patient specimens were used to determine both BDNF and TrkB mRNA levels. The expression of these proteins in their primary and metastatic tumors was investigated by immunohistochemistry. CRC cell lines and recombinant BDNF and K252a (a selective pharmacological pan-Trk inhibitor) were used for in vitro cell viability, migration, invasion, anoikis resistance and in vivo peritoneal metastasis assays. Tissue BDNF mRNA was associated with liver and peritoneal metastasis. Tissue TrkB mRNA was also associated with lymph node metastasis. The co-expression of BDNF and TrkB was associated with liver and peritoneal metastasis. Patients with higher BDNF, TrkB, and co-expression of BDNF and TrkB had a significantly poor prognosis. BDNF increased tumor cell viability, migration, invasion and inhibited anoikis in the TrkB-expressing CRC cell lines. These effects were suppressed by K252a. In mice injected with DLD1 co-expressing BDNF and TrkB, and subsequently treated with K252a, peritoneal metastatic nodules was found to be reduced, as compared with control mice. BDNF/TrkB signaling may thus be a potential target for treating peritoneal carcinomatosis arising from colorectal cancer.

  2. Sulindac and Celecoxib regulate cell cycle progression by p53/p21 up regulation to induce apoptosis during initial stages of experimental colorectal cancer.

    Science.gov (United States)

    Vaish, Vivek; Rana, Chandan; Piplani, Honit; Vaiphei, Kim; Sanyal, Sankar Nath

    2014-03-01

    In the present study we have elaborated the putative mechanisms could be followed by the non-steroidal anti-inflammatory drugs (NSAIDs) viz. Sulindac and Celecoxib in the regulation of cell cycle checkpoints along with tumor suppressor proteins to achieve their chemopreventive effects in the initial stages of experimental colorectal cancer. Male Sprague-Dawley rats were administered with 1,2-dimethylhydrazine dihydrochloride (DMH) to produce early stages of colorectal carcinogenesis. The mRNA expression profiles of various target genes were analyzed by RT-PCR and validated by quantitative real-time PCR, whereas protein expression was analyzed by Western blotting. Nuclear localization of transcription factors or other nuclear proteins was analyzed by electrophoretic mobility shift assay and immunofluorescence. Flowcytometry was performed to analyze the differential apoptotic events and cell cycle regulation. Molecular docking studies with different target proteins were also performed to deduce the various putative mechanisms of action followed by Sulindac and Celecoxib. We observed that DMH administration has abruptly increased the proliferation of colonic cells which is macroscopically visible in the form of multiple plaque lesions and co-relates with the disturbed molecular mechanisms of cell cycle regulation. However, co-administration of NSAIDs has shown regulatory effects on cell cycle checkpoints via induction of various tumor suppressor proteins. We may conclude that Sulindac and Celecoxib could possibly follow p53/p21 mediated regulation of cell proliferation, where down regulation of NF-κB signaling and activation of PPARγ might serve as important additional events in vivo.

  3. Colorectal Cancer Stem Cells and Cell Death

    Energy Technology Data Exchange (ETDEWEB)

    Catalano, Veronica [Department of Surgical and Oncological Sciences, University of Palermo, Via Liborio Giuffrè 5, 90127 Palermo, PA (Italy); Gaggianesi, Miriam [Department of Surgical and Oncological Sciences, University of Palermo, Via Liborio Giuffrè 5, 90127 Palermo, PA (Italy); Department of Cellular and Molecular Oncology, IRCCS Fondazione Salvatore Maugeri, Via Salvatore Maugeri, 27100 Pavia, PV (Italy); Spina, Valentina; Iovino, Flora [Department of Surgical and Oncological Sciences, University of Palermo, Via Liborio Giuffrè 5, 90127 Palermo, PA (Italy); Dieli, Francesco [Departement of Biopathology and Medicine Biotechnologies, University of Palermo, Via Liborio Giuffrè 5, 90127 Palermo, PA (Italy); Stassi, Giorgio, E-mail: giorgio.stassi@unipa.it [Department of Surgical and Oncological Sciences, University of Palermo, Via Liborio Giuffrè 5, 90127 Palermo, PA (Italy); Department of Cellular and Molecular Oncology, IRCCS Fondazione Salvatore Maugeri, Via Salvatore Maugeri, 27100 Pavia, PV (Italy); Todaro, Matilde [Department of Surgical and Oncological Sciences, University of Palermo, Via Liborio Giuffrè 5, 90127 Palermo, PA (Italy)

    2011-04-11

    Nowadays it is reported that, similarly to other solid tumors, colorectal cancer is sustained by a rare subset of cancer stem–like cells (CSCs), which survive conventional anticancer treatments, thanks to efficient mechanisms allowing escape from apoptosis, triggering tumor recurrence. To improve patient outcomes, conventional anticancer therapies have to be replaced with specific approaches targeting CSCs. In this review we provide strong support that BMP4 is an innovative therapeutic approach to prevent colon cancer growth increasing differentiation markers expression and apoptosis. Recent data suggest that in colorectal CSCs, protection from apoptosis is achieved by interleukin-4 (IL-4) autocrine production through upregulation of antiapoptotic mediators, including survivin. Consequently, IL-4 neutralization could deregulate survivin expression and localization inducing chemosensitivity of the colon CSCs pool.

  4. New practical synthesis of indazoles via condensation of o-fluorobenzaldehydes and their O-methyloximes with hydrazine.

    Science.gov (United States)

    Lukin, Kirill; Hsu, Margaret C; Fernando, Dilinie; Leanna, M Robert

    2006-10-13

    The reaction of o-fluorobenzaldehydes and their O-methyloximes with hydrazine has been developed as a new practical synthesis of indazoles. Utilization of the methyloxime derivatives of benzaldehydes (in the form of the major E-isomers) in this condensation effectively eliminated a competitive Wolf-Kishner reduction to fluorotoluenes, which was observed in the direct preparations of indazoles from aldehydes. Reaction of Z-isomers of methyloximes with hydrazine resulted in the formation of 3-aminoindazoles via a benzonitrile intermediate.

  5. Association between phytosterol intake and colorectal cancer risk: a case-control study.

    Science.gov (United States)

    Huang, Jing; Xu, Ming; Fang, Yu-Jing; Lu, Min-Shan; Pan, Zhi-Zhong; Huang, Wu-Qing; Chen, Yu-Ming; Zhang, Cai-Xia

    2017-03-01

    A study in rodent models showed that phytosterols protected against colon carcinogenesis, probably by inhibiting dysregulated cell cycle progression and inducing cellular apoptosis. However, epidemiological studies on the relationship between phytosterols and colorectal cancer risk are quite limited. The aim of this study was to investigate dietary phytosterol intake in relation to colorectal cancer risk in the Chinese population. A case-control study was conducted from July 2010 to June 2016, recruiting 1802 eligible colorectal cancer cases plus 1813 age (5-year interval) and sex frequency-matched controls. Dietary information was collected by using a validated FFQ. The OR and 95 % CI of colorectal cancer risk were assessed by multivariable logistic regression models. A higher total intake of phytosterols was found to be associated with a 50 % reduction in colorectal cancer risk. After adjusting for various confounders, the OR of the highest quartile intake compared with the lowest quartile intake was 0·50 (95 % CI 0·41, 0·61, P trendcolorectal cancer risk. However, stigmasterol intake was related to an increased risk of colorectal cancer. No statistically significant association was found between β-sitostanol and colorectal cancer risk. Stratified analysis by sex showed that the positive association of stigmasterol intake with colorectal cancer risk was found only in women. These data indicated that the consumption of total phytosterols, β-sitosterol, campesterol and campestanol is inversely associated with colorectal cancer risk in a Chinese population.

  6. Academic colorectal surgery job search.

    Science.gov (United States)

    Kalady, Matthew F

    2014-06-01

    The field of academic colorectal surgery encompasses a vast array of possibilities. Clinical care accompanied by research, teaching, innovation, and/or administration provides the foundation for what is considered an academic career. For those choosing academic colorectal surgery, the process of finding and selecting a first job can provoke much angst. This article describes some strategies to approach the academic colorectal job search and provides insight into deciding a career focus, exploring relevant positions, weighing specific factors, and negotiating your first offer.

  7. Ascorbic Acid Assisted Synthesis of Cobalt Oxide Nanostructures, Their Electrochemical Sensing Application for the Sensitive Determination of Hydrazine

    Science.gov (United States)

    Tahira, Aneela; Nafady, Ayman; Baloach, Quarratulain; Sirajuddin; Sherazi, Syed Tufail Hussain; Shaikh, Tayyaba; Arain, Munazza; Willander, Magnus; Ibupoto, Zafar Hussain

    2016-07-01

    This study describes, the synthesis of cobalt oxide nanostructures using ascorbic acid as a growth directing agent by the hydrothermal method. Ascorbic acid is used for the first time for the synthesis of cobalt oxide nanostructures and a unique morphology is prepared in the present study. The cobalt oxide nanostructures were characterized by scanning electron microcopy, x-ray diffraction, and x-ray photoelectron spectroscopy techniques. These analytical techniques demonstrated well defined morphology, good crystalline quality, and high purity of as prepared cobalt oxide nanostructures. The glassy carbon electrode was modified with cobalt oxide nanostructures for the development of a sensitive and selective electrochemical hydrazine sensor. The developed hydrazine sensor exhibits a linear range of 2-24 μM. The sensitivity and limit of detection of presented hydrazine sensors are 12,734 μA/mM/cm2 and 0.1 μM respectively. The developed hydrazine sensor is highly selective, stable, and reproducible. The proposed sensor is successfully applied for the detection of hydrazine from different water samples. The present study provides the development of an alternative tool for the reliable monitoring of hydrazine from environmental and biological samples.

  8. 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...... advancements in the field of colorectal cancer....

  9. Inositol hexaphosphate suppresses colorectal cancer cell proliferation via the Akt/GSK-3β/β-catenin signaling cascade in a 1,2-dimethylhydrazine-induced rat model.

    Science.gov (United States)

    Yu, Wenyang; Liu, Cuiping; Li, Xin; Yang, Fuguo; Cheng, Lixue; Liu, Chang; Song, Yang

    2017-06-15

    Colorectal cancer (CRC) is common worldwide, and most treatments for CRC have undesirable side effects. Many researchers have demonstrated that inositol hexaphosphate (IP6) has potent anticarcinogenic activity against CRC and no apparent toxicity to normal cells. However, the underlying mechanism is still unclear. In this study, we investigated the anticancer and anti-proliferative properties of IP6 in CRC and its possible mechanisms during this chemopreventive process. We examined the expression of genes related to the PI3K/Akt and Wnt pathways at the transcriptional and translational levels in a DMH-induced rat CRC model following IP6 administration. In addition, we also conducted cell proliferation analysis. The results demonstrated that IP6 could inhibit tumors, in terms of tumor incidence, number, weight and volume in DMH-induced rats. Additionally, Akt and c-Myc mRNA levels were significantly decreased. IP6 was also shown to downregulate Akt, pAkt, pGSK-3β, and c-Myc protein expression and upregulate pβ-catenin protein expression. Furthermore, tumor tissues from IP6-treated rats showed decreased proliferation. In conclusion, the anti-proliferative effect of IP6 may be related to crosstalk between the PI3K/Akt and Wnt pathways, revealing a potential mechanism of CRC inhibition by IP6 in our model. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. Self-regulating heater application to Shuttle/Centaur hydrazine fuel line thermal control

    Science.gov (United States)

    Unkrich, David B.

    1987-01-01

    The Shuttle/Centaur high energy upper stage vehicle thermal environments were more severe than previous Centaur vehicle thermal environments, creating need for a new hydrazine fuel line thermal control technique. Constant power heaters did not satisfy power dissipation requirements, because the power required to maintain fuel line thermal control during cold conditions exceeded the maximum power allowable during hot conditions. Therefore, a Raychem Thermolimit self-regulating heater was selected for this application, and was attached to the hydrazine fuel line with Kapton and aluminum foil tapes. Fuel line/heater thermal modeling and subsequent thermal vacuum chamber testing simulated heater thermal performance during all worst-case Shuttle/Centaur thermal environmental conditions. Fuel line temperatures were maintained between the 4C to 71C limits during all analytical and test cases. Finally, the thermal model predictions were correlated with the test data, thereby ensuring that the model would provide satisfactory predictions for future missions and/or vehicles.

  11. 2-(Hetero(aryl)methylene)hydrazine-1-carbothioamides as potent urease inhibitors.

    Science.gov (United States)

    Saeed, Aamer; Imran, Aqeel; Channar, Pervaiz A; Shahid, Mohammad; Mahmood, Wajahat; Iqbal, Jamshed

    2015-02-01

    A small series of 2-(hetero(aryl)methylene) hydrazine-1-carbothioamides including two aryl derivatives was synthesized and tested for their inhibitory activity against urease. Compound (E)-2-(Furan-2-ylmethylene) hydrazine-1-carbothioamide (3f), having a furan ring, was the most potent inhibitor of urease with an IC50 value of 0.58 μM. Molecular modeling was carried out through docking the designed compounds into the urease binding site to predict whether these derivatives have analogous binding mode to the urease inhibitors. The study revealed that all of the tested compounds bind with both metal atoms at the active site of the enzyme. The aromatic ring of the compounds forms ionic interactions with the residues, Ala(440), Asp(494), Ala(636), and Met(637).

  12. Towards Safer Rocket Fuels: Hypergolic Imidazolylidene-Borane Compounds as Replacements for Hydrazine Derivatives.

    Science.gov (United States)

    Huang, Shi; Qi, Xiujuan; Liu, Tianlin; Wang, Kangcai; Zhang, Wenquan; Li, Jianlin; Zhang, Qinghua

    2016-07-11

    Currently, toxic and volatile hydrazine derivatives are still the main fuel choices for liquid bipropellants, especially in some traditional rocket propulsion systems. Therefore, the search for safer hypergolic fuels as replacements for hydrazine derivatives has been one of the most challenging tasks. In this study, six imidazolylidene-borane compounds with zwitterionic structure have been synthesized and characterized, and their hypergolic reactivity has been studied. As expected, these compounds exhibited fast spontaneous combustion upon contact with white fuming nitric acid (WFNA). Among them, compound 5 showed excellent integrated properties including wide liquid operating range (-70-160 °C), superior loading density (0.99 g cm(-3) ), ultrafast ignition delay times with WFNA (15 ms), and high specific impulse (303.5 s), suggesting promising application potential as safer hypergolic fuels in liquid bipropellant formulations.

  13. Formation of raspberry like cobalt particles with hydrazine reduction in a polyol route

    Science.gov (United States)

    Khe, Cheng Seong; Aziz, Azizan; Lockman, Zainovia; Rajalingam, Sokkalingam; Merican, Zulkifli; Vasant, Pandian

    2016-11-01

    This work describes the effect of hydrazine hydrate on the formation of the raspberry-like morphology of the cobalt nanomaterials in a polyol route. In the synthesis, the molar ratio of N2H4 to Co2+was varied from 2.5 to 10. At the beginning with low molar ratio, spherical microspheres were formed. When the molar ratio was increased to 5 and above, final morphology of the cobalt nanomaterials became raspberry-like. This might be attributed to the absorption of the hydrazine complex of cobalt nanoparticles at certain facets during their growth stage and later self-assembled into the raspberry shaped microparticles. The plausible formation mechanism were proposed.

  14. Microwave-assisted synthesis of carbon-supported carbides catalysts for hydrous hydrazine decomposition

    Science.gov (United States)

    Mnatsakanyan, Raman; Zhurnachyan, Alina R.; Matyshak, Valery A.; Manukyan, Khachatur V.; Mukasyan, Alexander S.

    2016-09-01

    Microwave-assisted synthesis of carbon-supported Mo2C and WC nanomaterials was studied. Two different routes were utilized to prepare MoO3 (WO3) - C precursors that were then subjected to microwave irradiation in an inert atmosphere. The effect of synthesis conditions, such as irradiation time and gas environment, was investigated. The structure and formation mechanism of the carbide phases were explored. As-synthesized nanomaterials exhibited catalytic activity for hydrous hydrazine (N2H4·H2O) decomposition at 30-70 °C. It was shown that the catalyst activity significantly increases if microwave irradiation is applied during the decomposition process. Such conditions permit complete conversion of hydrazine to ammonia and nitrogen within minutes. This effect can be attributed to the unique nanostructure of the catalysts that includes microwave absorbing carbon and active carbide constituents.

  15. The Effects of Hydrazines and Related Compounds on Calcium Calmodulin Regulated Synaptic Processes

    Science.gov (United States)

    1983-07-01

    4F -631 0 1984 E IS. KEY WORDS (Continue on reverse side if necessary and identify by block nunmber) Calmodulin, protein kinase, adenylate cyclase...hydrazines, organophosphates, C) calcium, synaptic processes, protein phosphorylation. 20. BSTRACT (Continue an reverse side it necessary mid Identify...Date Entered) %. % V -*> ~ * - Unclassified SECURITY CLASIFICATION OF THIS PAGE(Vhun Dots tn er@Q 20. A BWT&CT continued, nmembrane fractions and

  16. Dimethyl hydrazine-1,2-dicarboxylate–triphenylphosphine oxide (1/1

    Directory of Open Access Journals (Sweden)

    Bogdan Doboszewski

    2011-07-01

    Full Text Available In the crystal structure of the title compound, C4H8N2O4·C18H15OP, two triphenylphosphine oxide molecules and two dimethyl hydrazine-1,2-dicarboxylate molecules are connected via N—H...O hydrogen bonds of moderate strength and are related via a twofold rotational axis. Weak Car—H... O contacts strengthen the crystal structure.

  17. Preparation of Peptide p-Nitroanilides using an Aryl Hydrazine Solid Support

    Energy Technology Data Exchange (ETDEWEB)

    Kwon, Y; Welsh, K; Mitchell, A R; Camarero, J A

    2004-08-05

    Peptide p-nitroanilides are useful compounds for studying protease activity, however the poor nucleophilicity of p-nitroaniline makes their preparation difficult. We describe a new efficient approach for the Fmoc-based synthesis of peptide p-nitroanilides using an aryl hydrazine resin. Mild oxidation of the peptide hydrazide resin yields a highly reactive acyl diazene, which efficiently reacts with weak nucleophiles. We have prepared several peptide p-nitroanilides, including substrates for the Lethal Factor protease from B. anthracis.

  18. Nanostructured SnO2 encapsulated guar-gum hybrid nanocomposites for electrocatalytic determination of hydrazine.

    Science.gov (United States)

    Malik, Priya; Srivastava, Manish; Verma, Ranjana; Kumar, Manish; Kumar, D; Singh, Jay

    2016-01-01

    The present article deals with synthesis of sol-gel derived tin dioxide (SnO2) nanoparticles encapsulated in to guar gum (GG) biopolymer as the organic-inorganic hybrid materials for the determination of hydrazine. The organic-inorganic hybrid combines the perfunctory strength offered by the inorganic SnO2 nanoparticles with flexible binding sites provided by the organic biopolymer (GG) solution by the ultrasonication. The phase identification, crystalline size, surface morphology and optical properties of prepared SnO2 and SnO2-GG nanocomposites has been investigated through FT-IR, XRD, SEM, AFM, TEM, UV-Vis, and PL techniques. The colloidal solution of SnO2 and GG is electrophoretically deposited (EPD) onto the indium tin-oxide (ITO) glass substrate and studied for the electrooxidation of hydrazine. Under the optimized experimental conditions, the linearity between the current response and the hydrazine concentration has been obtained in the range of 2-22 mM, with a low detection limit of 2.76 mM and a high sensitivity of 5.72 μA cm(-2). Based on the linear increase in amperometric current, a sensitive hydrazine electrochemical sensor is constructed. The proposed SnO2-GG/ITO electrode shows a good response time (35s), reproducibility, and long-term stability. The obtained results suggest that SnO2-GG nanocomposites electrode provides a favorable sensing platform for the electrochemical studies. In addition, the cyclic voltammetry (CV) studies are used to evaluate the kinetic parameters.

  19. Design, Synthesis and Biological Activities of Novel Benzoyl Hydrazines Containing Pyrazole

    Institute of Scientific and Technical Information of China (English)

    闫涛; 于淑晶; 刘鹏飞; 刘卓; 王宝雷; 熊丽霞; 李正名

    2012-01-01

    In search of environmentally benign compounds with high biological activity, low toxicity and low resistance, 8 novel benzoyl hydrazines containing pyrazole were designed and synthesized. All compounds were characterized by I H NMR spectra and HRMS. The preliminary results of biological activity assessment indicated that most of title compounds exhibited certain insecticidal activities against M),thimna separata Walker at 200 mg L-1 but excellent fungicidal activities against six fungus at 50 mg L-1, which were better than the control.

  20. Dose response of hydrazine - Deproteinated tooth enamel under blue light stimulation

    Energy Technology Data Exchange (ETDEWEB)

    Yuece, Ulkue Rabia, E-mail: ulkuyuce@hotmail.co [Ankara University, Faculty of Engineering, Department of Engineering Physics, 06100, Tandogan - Ankara (Turkey); Meric, Niyazi, E-mail: meric@ankara.edu.t [Ankara University, Faculty of Engineering, Department of Engineering Physics, 06100, Tandogan - Ankara (Turkey); Atakol, Orhan, E-mail: atakol@science.ankara.edu.t [Ankara University, Science Faculty, Department of Chemistry, 06100, Tandogan - Ankara (Turkey); Yasar, Fusun, E-mail: ab121310@adalet.gov.t [Council of Forensic Medicine, Ankara Branch, Ankara (Turkey)

    2010-08-15

    The beta dose response and Optically Stimulated Luminescence (OSL) signal stability characteristics of human tooth enamel deproteinated by hydrazine reagent under blue photon stimulation are reported. Removal of the protein organic component of tooth enamel resulted in a higher OSL sensitivity and slower fading of OSL signals. The effect of chemical sample preparation on the enamel sample sensitivity is discussed and further steps to make this deproteinization treatment suitable for in vitro dose reconstruction studies are suggested.

  1. Highly Sensitive Hydrazine Chemical Sensor Based on CNT-PdPt Nanocomposites

    Directory of Open Access Journals (Sweden)

    Sung Phil Kim

    2015-01-01

    Full Text Available Bimetallic PdPt nanoparticles were prepared using the chemical reduction method. The PdPt nanoparticles were successfully deposited on thiolated carbon nanotubes (CNTs to form a CNT-PdPt nanocomposite as an electron mediator for the fabrication of a hydrazine sensor. The PdPt nanoparticles had an average particle size of 2.3 nm and were well dispersed on the surfaces of the CNTs in the prepared CNT-PdPt nanocomposite, as demonstrated using transmission electron microscopy (TEM, energy dispersive X-ray spectroscopy (EDX, and X-ray diffraction (XRD. Based on X-ray photoelectron spectroscopy (XPS results, the estimated proportions of Pd and Pt in the CNT-PdPt nanocomposite were approximately 3.0% and 3.2%, respectively. A fabricated chemical sensor based on CNT-PdPt was found to exhibit better amperometric activity with respect to the hydrazine oxidation reaction than CNT-Pd, CNT-Pt, and commercial Pd/C and Pt/C catalysts. This sensor exhibited a linear range of 0.55–1,200 μM and a detection limit of 0.28 μM (S/N = 3 with a fast response time (within 5 s. Furthermore, the sensor could be used repeatedly for the consecutive detection of hydrazine with good reusability and storage stability. These properties demonstrate that the CNT-PdPt nanocomposite is a promising electron mediator for the fabrication of amperometric hydrazine sensors.

  2. Reactivity of 4-tert-Butyldimethylsiloxy-1,2,3,6-tetrahydropyridines with Hydrazines

    Directory of Open Access Journals (Sweden)

    Manuel Medarde

    2006-11-01

    Full Text Available The reactivity of 6-(nitrophenyl or trimethoxyphenyl-4-tert-butyldimethyl- siloxy-1,2,3,6-tetrahydropyridine derivatives with hydrazines under acid conditions is described. The structure of the products isolated − hydrazones, pyrazolines or pyridazinones − depended on the conditions used. In addition, a systematic study of the reaction outcomes was carried out by introducing variations on the substituents of the tetrahydropyridine ring.

  3. Study on the Reaction Between Methyl Hydrazine and Formaldehyde in Nitric Acid Medium

    Institute of Scientific and Technical Information of China (English)

    LI; Chuan-bo; CAO; Zhi; BIAN; Xiao-yan; XIAN; Liang; YAN; Tai-hong; ZHENG; Wei-fang

    2012-01-01

    <正>To make sure whether the reaction between formaldehyde and methyl hydrazine (MMH) could happen in dilute nitric acid solution, the condensation reaction between the two ones was investigated at 16 ℃. The reaction was slow and it took over 5 hours to reach the balance and the solution turned yellow at last. The maximum absorption peaks of the product existed at 340 nm and 400-450 nm, respectively.

  4. (E)-1-Benzyl-idene-2,2-diphenyl-hydrazine.

    Science.gov (United States)

    Mendoza, Angel; Meléndrez-Luevano, Ruth; Cabrera-Vivas, Blanca M; Lozano-Márquez, Claudia D; Carranza, Vladimir

    2012-02-01

    The asymmetric unit of the title compound, C(19)H(16)N(2), contains two independent mol-ecules, both of which show an E configuration with respect to the C=N bond. The dihedral angles between the phenyl rings bonded to the hydrazine group are 81.00 (10) and 88.34 (8)° in the two mol-ecules. Inter-molecular C-H⋯π inter-actions are observed in the crystal structure.

  5. The Decomposition of Hydrazine in the Gas Phase and over an Iridium Catalyst

    Energy Technology Data Exchange (ETDEWEB)

    Schmidt, Michael W. [Ames Laboratory; Gordon, Mark S. [Ames Laboratory

    2013-09-30

    Hydrazine is an important rocket fuel, used as both a monopropellant and a bipropellant. This paper presents theoretical results to complement the extensive experimental studies of the gas phase and Ir catalyzed decompositions involved in the monopropellant applications of hydrazine. Gas phase electronic structure theory calculations that include electron correlation predict that numerous molecular and free radical reactions occur within the same energy range as the basic free radical pathways: NN bond breaking around 65 kcal/mol and NH bond breaking around 81 kcal/mol. The data suggest that a revision to existing kinetics modeling is desirable, based on the energetics and the new elementary steps reported herein. A supported Ir-6 octahedron model for the Shell 405 Iridium catalyst used in thrusters was developed. Self-Consistent Field and electron correlation calculations (with core potentials and associated basis sets) find a rich chemistry for hydrazine on this catalyst model. The model catalyst provides dramatically lower NN and NH bond cleavage energies and an even smaller barrier to breaking the NH bond by NH2 abstractions. Thus, the low temperature decomposition over the catalyst is interpreted in terms of consecutive NH2 abstractions to produce ammonia and nitrogen. The higher temperature channel, which has hydrogen and nitrogen products, may be due to a mixture of two mechanisms. These two mechanisms are successive NH cleavages with surface H + H recombinations, and the same type of assisted H-2 eliminations found to occur in the gas phase part of this study.

  6. Alkalization of steam and condensate with 2-amino-1-butanol and hydrazine; Alkalisering av aanga och kondensat med butanolamin och hydrazin

    Energy Technology Data Exchange (ETDEWEB)

    Falk, I. [Studsvik Material AB, Nykoeping (Sweden)

    1996-04-01

    To maintain a low corrosion level in steam- and condensate systems at power and industrial plants, an alkalization of the steam is needed. A low corrosion level lowers the risk of operation disturbances and reduces the cost of the condensate clean up. A better knowledge in the behavior of the alkalis will improve the possibilities to avoid the corrosion attacks. In this work experimental measurements have been carried out during steam boiler conditions as temperature, continuous steam generation and condensation. It has been found that the volatility of 2-amino-1-butanol is very low during stationary dynamic conditions at 250 deg C and 120 deg C. To achieve a high ph-value in the final condensate a very high concentration of 2-amino-1-butanol is thus needed especially when the steam contains acidic compounds. The alkalization effect is obtained from ammonia which is created by thermal decomposition of hydrazine in the boiler water. It is necessary to carry out experimental investigations showing the thermal stability of organic compounds in boiler water before it is possible to recommend them as better volatile alkalis than ammonia and hydrazine. 6 refs, 13 figs

  7. The effect of statins in colorectal cancer is mediated through the bone morphogenetic protein pathway

    NARCIS (Netherlands)

    Kodach, Liudmila L.; Bleuming, Sylvia A.; Peppelenbosch, Maikel P.; Hommes, Daniel W.; Van Den Brink, Gus R.; Hardwick, James C. H.

    2007-01-01

    Background & Aims: Epidemiological evidence suggests that statins prevent colorectal cancer (CRC), but the biological mechanism remains obscure. Statins induce bone morphogenetic protein (BMP) expression in bone cells. We have previously shown that BMPs act as tumor suppressors in CRC. We

  8. CXCL12/CXCR4 axis induced miR-125b promotes invasion and confers 5-fluorouracil resistance through enhancing autophagy in colorectal cancer

    Science.gov (United States)

    Yu, Xinfeng; Shi, Wenna; Zhang, Yuhang; Wang, Xiaohui; Sun, Shiyue; Song, Zhiyu; Liu, Man; Zeng, Qiao; Cui, Shuxiang; Qu, Xianjun

    2017-01-01

    The activation of CXCL12/CXCR4 axis is associated with potential progression of cancer, such as invasion, metastasis and chemoresistance. However, the underlying mechanisms of CXCL12/CXCR4 axis and cancer progression have been poorly explored. We hypothesized that miRNAs might be critical downstream mediators of CXCL12/CXCR4 axis involved in cancer invasion and chemoresistance in CRC. In human CRC cells, we found that the activation of CXCL12/CXCR4 axis promoted epithelial-mesenchymal transition (EMT) and concurrent upregulation of miR-125b. Overexpression of miR-125b robustly triggered EMT and cancer invasion, which in turn enhanced the expression of CXCR4. Importantly, the reciprocal positive feedback loop between CXCR4 and miR-125b further activated the Wnt/β-catenin signaling by targeting Adenomatous polyposis coli (APC) gene. There was a negative correlation of the expression of miR-125b with APC mRNA in paired human colorectal tissue specimens. Further experiments indicated a role of miR-125b in conferring 5-fluorouracil (5-FU) resistance in CRC probably through increasing autophagy both in vitro and in vivo. MiR-125b functions as an important downstream mediator upon the activation of CXCL12/CXCR4 axis that involved in EMT, invasion and 5-FU resistance of CRC. These findings shed a new insight into the role of miR-125b and provide a potential therapeutic target in CRC. PMID:28176874

  9. Transforming Growth Factor Beta-Induced Factor 2-Linked X (TGIF2LX Regulates Two Morphogenesis Genes, Nir1 and Nir2 in Human Colorectal

    Directory of Open Access Journals (Sweden)

    Gholam Reza Mobini

    2016-05-01

    Full Text Available A member of homeodomain protein namely TGIF2LX has been implicated as a tumor suppressor gene in human malignancy as well as in spermatogenesis. However, to our knowledge, dynamic functional evidence of the TGIF2LX has not yet been provided. The aim of the present study was to investigate the human TGIF2LX target gene(s using a cDNA-AFLP as a differential display method. A pEGFP-TGIF2LX construct containing the wild-type TGIF2LX cDNA was stably transfected into SW48 cells. UV microscopic analysis and Real-time RT-PCR were used to confirm TGIF2LX expression. The mRNA expressions of TGIF2LX in transfected SW48 cells, the cells containing empty vector (pEGFP-N, and untransfected cells were compared. Also, a Real-time PCR technique was applied to validate cDNA-AFLP results. The results revealed a significant down-regulation and up-regulationby TGIF2LX of Nir1 and Nir2 genes, respectively. The genes are engaged in the cell morphogenesis process. Our findings may provide new insight into the complex molecular pathways underlying colorectal cancer development.

  10. Transforming Growth Factor Beta-Induced Factor 2-Linked X (TGIF2LX) Regulates Two Morphogenesis Genes, Nir1 and Nir2 in Human Colorectal.

    Science.gov (United States)

    Mobini, Gholam Reza; Ghahremani, Mohammad Hossein; Amanpour, Saeid; Dehpour, Ahmad Reza; Akbari, Abolfazl; Hoseiniharouni, Seyed Mojtaba; Muhammadnejad, Samad; Sheikhzade, Maryam; Abedkhojasteh, Hoda; Mohebi, Masoumeh; Bolhassani, Manzar; Heidari, Mansour

    2016-05-01

    A member of homeodomain protein namely TGIF2LX has been implicated as a tumor suppressor gene in human malignancy as well as in spermatogenesis. However, to our knowledge, dynamic functional evidence of the TGIF2LX has not yet been provided. The aim of the present study was to investigate the human TGIF2LX target gene(s) using a cDNA-AFLP as a differential display method. A pEGFP-TGIF2LX construct containing the wild-type TGIF2LX cDNA was stably transfected into SW48 cells. UV microscopic analysis and Real-time RT-PCR were used to confirm TGIF2LX expression. The mRNA expressions of TGIF2LX in transfected SW48 cells, the cells containing empty vector (pEGFP-N), and untransfected cells were compared. Also, a Real-time PCR technique was applied to validate cDNA-AFLP results. The results revealed a significant down-regulation and up-regulationby TGIF2LX of Nir1 and Nir2 genes, respectively. The genes are engaged in the cell morphogenesis process. Our findings may provide new insight into the complex molecular pathways underlying colorectal cancer development.

  11. Second Cancers After Colorectal Cancer

    Science.gov (United States)

    ... after colorectal cancer. To help maintain good health, colorectal cancer survivors should also: Get to and stay at a healthy weight Keep physically active Eat a healthy diet , with an emphasis on plant foods Limit alcohol to no more than 1 drink per day ...

  12. Endoscopic detection and treatment of colorectal polyps

    NARCIS (Netherlands)

    Belderbos, TDG

    2017-01-01

    Colorectal cancer (CRC) is the third most commonly diagnosed malignancy and the fourth leading cause of cancer related mortality worldwide. Most colorectal cancers arise form premalignant colorectal polyps. Colorectal polyps can be roughly subdivided into hyperplastic, non-malignant polyps and

  13. The effect of COX-2 inhibitor on capecitabine-induced hand-foot syndrome in patients with stage II/III colorectal cancer: a phase II randomized prospective study.

    Science.gov (United States)

    Zhang, Rong-Xin; Wu, Xiao-Jun; Lu, Shi-Xun; Pan, Zhi-Zhong; Wan, De-Sen; Chen, Gong

    2011-06-01

    Hand-foot syndrome (HFS) is a common adverse event that can be induced by capecitabine. It is hypothesized that capecitabine (Hoffmann-La Roche Inc.) based chemotherapy can cause overexpression of COX-2 in tumor and healthy tissue, which finally induced HFS in hands and feet. Based on this, we believed that a selected COX-2 inhibitor (celecoxib, Pfizer Pharmaceuticals LLC) could ease HFS. We designed a prospective clinical study to test the hypothesis. From August 2008 to January 2010, 110 patients with stage II/III colorectal cancer who were eligible for adjuvant chemotherapy were enrolled in the study and divided into 4 groups by random, but 9 patients did not finish at least 4 cycles of chemotherapy. There were sixteen patients in capecitabine group, and fifteen patients in capecitabine and celecoxib group. Thirty-four patients were in XELOX (capecitabine plus oxaliplatine) group, and thirty-six patients in XELOX+ celecoxib group. All 101 patients finished chemotherapy and follow-up interviews. The group that had received capecitabine and celecoxib had a significantly reduced frequency of  >grade 1 hand-foot syndrome (29 vs. 72% P grade 2 (11.76% vs. 30% P = 0.024). Five patients experienced grade 3 HFS in capecitabine group and only 1 patient had grade 3 HFS in capecitabine and celecoxib group. There were 5 patients in capecitabine group who refused to go on chemotherapy because of HFS, but there was none in capecitabine and celecoxib group. From the result of this study, we could learn that celecoxib could reduce HFS that was induced by capecitabine. So we recommend that celecoxib can be used in capecitabine-based chemotherapy.

  14. Intramolecular Electron Transfer in Bis(tetraalkyl Hydrazine) and Bis(hydrazyl) Radical Cations.

    Science.gov (United States)

    Chang, Hao

    A series of multicyclic bis(hydrazine) and bis(diazenium) compounds connected by relatively rigid hydrocarbon frameworks were prepared for the study of intramolecular electron transfer. The thermodynamics of electron removal of these compounds was investigated by cyclic voltammetry. The difference between the first and second oxidation potentials for the 4 sigma-bonded species was found to be larger for the bis(hydrazyl) radical systems than for the bis(hydrazines) by ca. 0.2 V (4.6 kcal/mol). This indicates a greater degree of interaction between the two nitrogen moieties for the hydrazyl systems, which is consistent with a greater degree of electronic coupling (H _{rm AB}) in these systems. The ESR spectra of the 4 sigma -bonded bis(hydrazine) radical cations indicate localized radical cations, which corresponds to slow intramolecular electron transfer on the ESR timescale. Conversely, the ESR spectra of the corresponding bis(hydrazyl) radical cation systems show nitrogen hyperfine splittings of a(4N) of ca. 4.5 G. This indicates that intramolecular electron transfer between the two nitrogen moieties is fast on the ESR timescale; the rate of exchange, k_ {rm ex} was estimated to be well above 1.9 times 10^8 s^{-1}. The contrast in exchange rates is consistent with the large geometry change upon oxidation which is characteristic of hydrazines. The hydrazyls undergo a smaller geometry change upon oxidation, and thus are expected to exhibit smaller inner-sphere reorganization energies. The optical spectra of these radical species was investigated in hopes of observing absorption bands corresponding to intramolecular electron transfer, as predicted by Hush theory. A broad absorption band was observed in the near IR region for the saturated bis(hydrazyl) radical cation system at 1060 nm (9420 cm^{-1} ) in acetonitrile at room temperature, and was accompanied by a narrower band at 1430 nm (6993 cm^ {-1}). The width of this band was estimated to be 545 nm (6496 cm^{-1

  15. Colorectal cancer surveillance in Hodgkin lymphoma survivors at increased risk of therapy-related colorectal cancer: study design.

    Science.gov (United States)

    Rigter, Lisanne S; Spaander, Manon C W; Moons, Leon M; Bisseling, Tanya M; Aleman, Berthe M P; de Boer, Jan Paul; Lugtenburg, Pieternella J; Janus, Cecile P M; Petersen, Eefke J; Roesink, Judith M; Raemaekers, John M M; van der Maazen, Richard W M; Cats, Annemieke; Bleiker, Eveline M A; Snaebjornsson, Petur; Carvalho, Beatriz; Lansdorp-Vogelaar, Iris; Jóźwiak, Katarzyna; Te Riele, Hein; Meijer, Gerrit A; van Leeuwen, Flora E; van Leerdam, Monique E

    2017-02-07

    molecular analyses in order to obtain more insight into colorectal carcinogenesis in Hodgkin lymphoma survivors. The Miscan-model will be used for cost-effectiveness analyses. Evaluation of the diagnostic performance, patient acceptance and burden of colorectal cancer surveillance is necessary for future implementation of an individualized colorectal cancer surveillance program for Hodgkin lymphoma survivors. In addition, more insight into treatment-induced colorectal carcinogenesis will provide the first step towards prevention and personalized treatment. This information may be extrapolated to other groups of cancer survivors. Registered at the Dutch Trial Registry (NTR): NTR4961 .

  16. Salinomycin inhibits the growth of colorectal carcinoma by targeting tumor stem cells.

    Science.gov (United States)

    Zhang, Chen; Tian, Yaping; Song, Feiyu; Fu, Changhao; Han, Bo; Wang, Yi

    2015-11-01

    Salinomycin is a monocarboxylic polyether antibiotic that has been reported to induce apoptosis in various types of cancer cells with specificity for cancer stem cells. However, its anticancer effect in colorectal cancer stem cells has never been reported. In the present study, we examined the ability of salinomycin to induce cell death in the colorectal cancer stem cell line CD44+EpCAM+ HCT-116, and we measured its in vivo tumor inhibition capacity. Salinomycin dose-dependently induced cytotoxicity in the CD44+EpCAM+ HCT-116 cells and inhibited colony formation. Salinomycin treatment was shown to induce apoptosis, as evidenced by nuclear fragmentation, an increase in the proportion of acridine orange/ethidium bromide-positive cells and an increase in the percentage of Annexin V-positive cells. Apoptosis was induced in colorectal cancer stem cells in a caspase-dependent manner, as shown by an increase in the levels of cleaved caspase-3, -8 and -9. JC-1 staining further revealed that salinomycin induced colorectal cancer cell apoptosis via the mitochondrial pathway. In addition, salinomycin treatment of xenograft mice inhibited the growth of tumors derived from the CD44+EpCAM+ HCT-116 cells. The present study demonstrated that the antibiotic salinomycin exerts an anti-colorectal cancer effect in vitro and in vivo, suggesting salinomycin as a potential drug for colorectal cancer therapy.

  17. Alcohol Intake, Smoking, and Colorectal Adenoma

    OpenAIRE

    Park, Yeong Mi; Cho, Chang Ho; Kim, Sung Hi; Lee, Jung Eun

    2014-01-01

    Background: Colorectal cancer is the third most common cancer in Korea. Because colorectal adenoma is a precursor lesion of colorectal cancer, primary prevention of colorectal adenomas may be important for reducing morbidity and mortality from the disease. The aim of this study is to examine the association of alcohol consumption and cigarette smoking in relation with colorectal adenoma in a cross-sectional study of Korean adults. Methods: A total of 366 participants who underwent colonoscopy...

  18. Complications in colorectal surgery.

    Science.gov (United States)

    Frischer, Jason S; Rymeski, Beth

    2016-12-01

    Colorectal pediatric surgery is a diverse field that encompasses many different procedures. The pullthrough for Hirschsprung disease, the posterior sagittal anorectoplasty for anorectal malformations including complex cloaca reconstructions and the ileal pouch anal anastomosis for ulcerative colitis and familial adenomatous polyposis present some of the most technically challenging procedures pediatric surgeons undertake. Many children prevail successfully following these surgical interventions, however, a small number of patients suffer from complications following these procedures. Anticipated postoperative problems are discussed along with medical and surgical strategies for managing these complications. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. Robotics in colorectal surgery.

    Science.gov (United States)

    Hance, J; Rockall, T; Darzi, A

    2004-01-01

    Minimally invasive surgery has been shown to offer many advantages to general surgical patients but has not been widely adopted for colorectal disease. Initial fears surrounding the oncological safety of laparoscopic colectomies have largely subsided but the technical challenges still remain. Surgical robots or telemanipulators present the laparoscopic surgeon with unrivaled dexterity and vision, which may allow colonic resections to be completed with greater ease. Although initial studies suggest promising results using currently available systems, it will take further time for patient benefits to be proven, therefore justifying the greater expense of operating with this new technology.

  20. 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.

  1. Carcinogenicity and chronic toxicity of hydrazine monohydrate in rats and mice by two-year drinking water treatment.

    Science.gov (United States)

    Matsumoto, Michiharu; Kano, Hirokazu; Suzuki, Masaaki; Katagiri, Taku; Umeda, Yumi; Fukushima, Shoji

    2016-04-01

    The carcinogenicity and chronic toxicity of hydrazine monohydrate was examined by administrating hydrazine monohydrate in drinking water to groups of 50 F344/DuCrj rats and 50 Crj:BDF1 mice of both sexes for two years. The drinking water concentration of hydrazine monohydrate was 0, 20, 40 or 80 ppm (wt/wt) for male and female rats and male mice; and 0, 40, 80 or 160 ppm for female mice. Survival rates of each group of males and females rats and mice were similar to the respective controls, except female rats administered 80 ppm. Two-year administration of hydrazine monohydrate produced an increase in the incidences of hepatocellular adenomas and carcinomas in rats of both sexes along with hepatic foci. In mice, the incidences of hepatocellular adenomas and carcinomas were increased in females, and significantly increased incidences of hepatocellular adenomas in females administered 160 ppm were observed. Thus, hydrazine monohydrate is carcinogenic in two species, rats and mice. Additionally, non-neoplastic renal lesions in rats and mice and non-neoplastic nasal lesions in mice were observed.

  2. An Improved Calibration Method for Hydrazine Monitors for the United States Air Force

    Energy Technology Data Exchange (ETDEWEB)

    Korsah, K

    2003-07-07

    This report documents the results of Phase 1 of the ''Air Force Hydrazine Detector Characterization and Calibration Project''. A method for calibrating model MDA 7100 hydrazine detectors in the United States Air Force (AF) inventory has been developed. The calibration system consists of a Kintek 491 reference gas generation system, a humidifier/mixer system which combines the dry reference hydrazine gas with humidified diluent or carrier gas to generate the required humidified reference for calibrations, and a gas sampling interface. The Kintek reference gas generation system itself is periodically calibrated using an ORNL-constructed coulometric titration system to verify the hydrazine concentration of the sample atmosphere in the interface module. The Kintek reference gas is then used to calibrate the hydrazine monitors. Thus, coulometric titration is only used to periodically assess the performance of the Kintek reference gas generation system, and is not required for hydrazine monitor calibrations. One advantage of using coulometric titration for verifying the concentration of the reference gas is that it is a primary standard (if used for simple solutions), thereby guaranteeing, in principle, that measurements will be traceable to SI units (i.e., to the mole). The effect of humidity of the reference gas was characterized by using the results of concentrations determined by coulometric titration to develop a humidity correction graph for the Kintek 491 reference gas generation system. Using this calibration method, calibration uncertainty has been reduced by 50% compared to the current method used to calibrate hydrazine monitors in the Air Force inventory and calibration time has also been reduced by more than 20%. Significant findings from studies documented in this report are the following: (1) The Kintek 491 reference gas generation system (generator, humidifier and interface module) can be used to calibrate hydrazine detectors. (2) The

  3. 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

  4. Spectral, thermal and X-ray studies on some new bis-hydrazine metal glyoxylates and bis-hydrazine mixed metal glyoxylates

    Energy Technology Data Exchange (ETDEWEB)

    Vikram, L. [Department of Chemistry, Government Arts College, Ooty, The Nilgiris, Udhagamandalam 643002 (India); Sivasankar, B.N. [Department of Chemistry, Government Arts College, Ooty, The Nilgiris, Udhagamandalam 643002 (India)]. E-mail: sivabickol@yahoo.com

    2007-01-01

    Bis-hydrazine complexes of metal glyoxylates and mixed metal glyoxylates of 3d-metal ions of the formula M(OOCCHO){sub 2}(N{sub 2}H{sub 4}){sub 2}, where M = Mg, Mn, Co, Ni, Cu, Zn or Cd and M{sub 1/3}Co{sub 2/3}(OOCCHO){sub 2}(N{sub 2}H{sub 4}){sub 2}, where M = Mg, Mn, Ni, Zn or Cd, respectively, have been prepared and studied. The compositions of the complexes have been determined by chemical analyses. The magnetic moments and electronic spectra suggest a high-spin octahedral geometry for the metal complexes. Infrared spectral data indicate the bidentate bridging by hydrazine molecules and monodentate coordination by glyoxylate ions in both the metal and mixed metal compounds. Thermogravimetry and differential thermal analyses in air have been used to study the thermal behaviour of the complexes. The simultaneous TG-DTA traces of all the complexes show multi-step deg.radation and the final products are found to be the respective metal oxides in the case of metal complexes and metal cobaltites in the case of mixed metal complexes. The final residues were identified by their X-ray powder diffraction patterns. X-ray powder diffraction patterns of the complexes including mixed metal complexes are almost superimposable with in each of the series indicating isomorphism. The metal cobaltites MCo{sub 2}O{sub 4}, where M = Mg, Mn, Ni, Zn or Cd were also prepared by decomposing the respective mixed metal complex in a pre-heated silica crucible at about 300 deg. C, and their identities were confirmed by chemical analyses, infrared spectra and X-ray powder diffraction.

  5. The study on specific umbilical blood Dc vaccine for Beige nude mice loaded human colorectal carcinoma to induce anti-tumor immunity.

    Science.gov (United States)

    Fu, Z-X; Han, J-S; Liu, F; Zhao, Z-L; Li, D-B; Shi, L; Dong, J-T; Zhou, Y; Cai, J-H

    2017-05-01

    This study is to observe the immunosuppression of CD137L transfected umbilical blood Dcs (Dendritic cell) vaccine to tumor development of SCID/ Beige nude mice. Samples of umbilical blood in the childbirth pregnant women were collected by density gradient centrifugation. Umbilical cord blood dendritic cells (Dcs) were transfected by specific CD137L via LipofectamineTM method and cells were harvested. Meanwhile, the peripheral blood of volunteers was collected to isolate Dcs, the Dcs were cultured for 5 days and hatched with SW-1116 cells antigen. The mature Dcs were harvested. The male SCID/Beige nude mice were subcutaneously injected with human SW-1116 cells in axillary to build colorectal carcinoma model as blank control (Blank). The naked peripheral blood Dc vaccine group (cPBMCs), the SW-1116 antigen-specific peripheral blood Dc vaccine group (pDcs) and the CD137L specific umbilical blood Dc vaccine group (tuDcs) were injected 24 h before tumor cells injection, respectively to recur the humanized immune reconstruction. The general life, living habits changes, tumor growing time and tumor size were observed. The nude mice were sacrificed 18 days after tumor formation. The tumor size, mice weight, in vitro tumor weight, liver weight and spleen weight of mice were recorded to evaluate the anti-tumor effect of the specific immune cells. The nude mice in pDcs group showed better general living condition, slower tumor growth, smaller tumor volume and no ulceration, necrosis, and death in nude mice. The tumor formation time in different groups was 4.71 ± 0.18 ds (blank), 7.71 ± 0.29 ds (cPBMCs), 7.86 ± 0.26 ds (pDcs) and 8.14 ± 0.69 ds (tuDcs) respectively. There were significant differences between blank and other three groups (F = 40.96, p human colon cancer in nude mice via increasing the number of immune effector cell in tumor microenvironment.

  6. Selumetinib and Cyclosporine in Treating Patients With Advanced Solid Tumors or Advanced or Metastatic Colorectal Cancer

    Science.gov (United States)

    2017-09-04

    Recurrent Colorectal Carcinoma; Solid Neoplasm; Stage IIIA Colorectal Cancer AJCC v7; Stage IIIB Colorectal Cancer AJCC v7; Stage IIIC Colorectal Cancer AJCC v7; Stage IVA Colorectal Cancer AJCC v7; Stage IVB Colorectal Cancer AJCC v7

  7. Danish Colorectal Cancer Group Database

    DEFF Research Database (Denmark)

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

    2016-01-01

    , 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......-term survivals since it started in 2001 for both patients with colon and rectal cancers.......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...

  8. Ammonia and hydrazine. Transition-metal-catalyzed hydroamination and metal-free catalyzed functionalization

    Energy Technology Data Exchange (ETDEWEB)

    Bertrand, Guy [Univ. of California, San Diego, CA (United States)

    2012-06-29

    The efficient and selective preparation of organic molecules is critical for mankind. For the future, it is of paramount importance to find catalysts able to transform abundant and cheap feedstocks into useful compounds. Acyclic and heterocyclic nitrogen-containing derivatives are common components of naturally occurring compounds, agrochemicals, cosmetics, and pharmaceuticals; they are also useful intermediates in a number of industrial processes. One of the most widely used synthetic strategies, allowing the formation of an N-C bond, is the addition of an N-H bond across a carbon-carbon multiple bond, the so-called hydroamination reaction. This chemical transformation fulfills the principle of “green chemistry” since it ideally occurs with 100% atom economy. Various catalysts have been found to promote this reaction, although many limitations remain; one of the most prominent is the lack of methods that permit the use of NH3 and NH2NH2 as the amine partners. In fact, ammonia and hydrazine have rarely succumbed to homogeneous catalytic transformations. Considering the low cost and abundance of ammonia (136 million metric tons produced in 2011) and hydrazine, catalysts able to improve the reactivity and selectivity of the NH3- and NH2NH2-hydroamination reaction, and more broadly speaking the functionalization of these chemicals, are highly desirable. In the last funded period, we discovered the first homogeneous catalysts able to promote the hydroamination of alkynes and allenes with ammonia and the parent hydrazine. The key feature of our catalytic systems is that the formation of catalytically inactive Werner complexes is reversible, in marked contrast to most of the known ammonia and hydrazine transition metal complexes. This is due to the peculiar electronic properties of our neutral ancillary ligands, especially their strong donating capabilities. However, our catalysts currently require

  9. Exenatide suppresses 1,2-dimethylhydrazine-induced colon cancer in diabetic mice: Effect on tumor angiogenesis and cell proliferation.

    Science.gov (United States)

    Tawfik, Mona K; Mohamed, Magda I

    2016-08-01

    Colon cancer is the third leading cause of cancer mortality worldwide, which results from interactions of different factors. It is frequently a pathological consequence of persistent inflammation. Diabetes affects several cancers and is positively correlated with the incidence of colon cancer. This study aimed to study the effect of exenatide in ameliorating inflammation, angiogenesis and cell proliferation in 1,2-dimethyl hydrazine (DMH) induced colorectal carcinoma in diabetic mice. Mice were randomly allocated into six groups, 8 mice each. Group 1: vehicle control group. Group 2: diabetic control group. Group 3: DMH control group: diabetic mice treated with DMH (20mg/kg/week,s.c.) for 15 week. Group 4: DMH-cisplatin group: mice received cisplatin (4mg/kg/week, i.p.). Groups 5 & 6: DMH-exenatide (10 and 20μg/kg) group: mice received exenatide (10 or 20μg/kg/day,s.c.), respectively. The present results highlighted an increase in angiogenic markers and cell proliferation in the DMH-diabetic group in comparison with the control group with greater expression of endothelial marker (CD34) and Ki-67 in colon tissue. Monotherapy with cisplatin or exenatide (10 and 20μg/kg) downregulated these markers to different extents. The current results provided evidence that exenatide represents a promising chemopreventive effect against DMH-induced colon carcinogenesis in diabetic mice, at least in part, attributed to its anti-angiogenic and anti-proliferative mechanisms.

  10. [Colorectal cancer in spouses of colorectal cancer patients].

    Science.gov (United States)

    Matsumata, T; Shikada, Y; Hasuda, S; Kishihara, F; Suehiro, T; Funahashi, S; Nagamatsu, Y; Iso, Y; Shima, I; Koga, C; Osamura, S; Ueda, M; Furuya, K; Sakino, I

    2000-06-01

    Married couples share home environments and life style for years. In the case of colorectal cancer, an association with insulin resistance was reported. We determined the presence of the insulin-resistance syndrome (IRS, 1 or more of the following: body mass index of > 25 kg/m2, diabetes, or hyperlipidemia) in 84 colorectal cancer patients, of whom 61 patients (73%) had IRS. The incidence of the distal colorectal cancer, which has been declining in the United States, was significantly higher in the IRS group than in the non-IRS group (75.4 vs 52.2%, p = 0.0400). Some mechanisms may promote the progression of mucosal lesions to invasive cancers in the distal colorectum. There were no significant differences with respect to the age (64.6 +/- 9.4 vs 64.3 +/- 11.3 yr, p = 0.8298), height (159 +/- 9 vs 157 +/- 8 cm, p = 0.1375), and body mass index (22.2 +/- 3.6 vs 22.4 +/- 2.7 kg/m2, p = 0.6364) between the patients and their spouses. In 84 couples in whom colorectal cancer develops at least in one may then not illustrate the nursery rhyme: "Jack Sprat could eat no fat, His wife could eat no lean...". The spouses had been married for an average of 38 years, and in 30 spouses who had been followed in a colorectal cancer screening, 5 developed colorectal cancer. To diminish the incidence of colorectal cancer in Japan, we might advise screening colonoscopy to the spouses of colorectal cancer patients, or déjà vu all over again?

  11. Electrocatalytic oxidation of hydrazine with alizarin red S as a homogenous mediator on the glassy carbon electrode

    Institute of Scientific and Technical Information of China (English)

    Mohammad; Mazloum-Ardakani; Roya; Mazidi; Mohammad; Hossein; Mashhadizadeh; Parvanah; Rahimi; Mohammad; Ali; Karimi

    2010-01-01

    Electro-catalytic oxidation and detection of hydrazine on a glassy carbon electrode,at pH 6.0,was studied by using alizarin red S as a homogeneous mediator.The overall number of electrons involved in the catalytic oxidation of hydrazine and that involved in the rate-determining step were four and one,respectively.The interfering effect of some cations,anions and organic compounds were examined.Peak current for this process varied linearly with the square root of the scan rate.The kinetic parameters,such as the electron transfer coefficient(α) and catalytic rate constant(k) ,were determined using cyclic voltammetry,linear sweep voltammetry and chronoamperometry.The electro-catalytic response was optimized with regards to the pH,scan rate,hydrazine concentration and other variables.

  12. Synthesis of the row of new functional derivatives of 7-arylalkyl-8-hydrazine theophyllines

    Directory of Open Access Journals (Sweden)

    Dmytro Korobko

    2016-03-01

    Full Text Available Hydrazine functional derivatives are widely used in medical practice as remedies applied for pharmacotherapy of depression, infection diseases, hypertension, diabetes, etc. It is worth mentioning that among obtained 7-R-8-hydrazine derivatives of 1,3-dimethylxantine promising substances have been identified. Due to the fact that literature sources display only results of occasional studies of the reactions between 7-R-8-hydrazine theophyllines and mono- or dicarbonyle substances, the use of other keto reagents for xanthine bicycle at 8th position functionalization will allow to explore synthetic potential of the last one, and with high probability may lead to obtaining original biologically active substances.Aim. To study types of reaction between 8-hydrazinyl-1,3-dimethyl-7-aryl alkyl-1H-purine-2,6(3H,7H-diones and a number of carbonyl containing reagents.Methods. A nucleophilic addition reaction followed by dehydration or ethanol splitting was used, as well as the complex of the modern analysis methods to confirm the structure and individuality of the synthesized substances.Results. Different directions of 8-hydrazinyl-1,3,-dimethyl-7(fenetyl-, 3-phenylpropyl-, 3-phenylalyl-1H-purine-2,6(3H,7H-diones chemical transformations in reactions with the appropriate carbonyl containing compounds have been studied experimentally. The structure of synthesized substances was confirmed by chromatography/mass and 1H NMR spectroscopy.Conclusion. The group of 7-arylalkyl-8-(3,5-R,R1-pyrazole-1-yltheophyllines, consisting of two functionally substituted bioactive heterocycles, has been synthesized by reaction between initial substances and selected mono- and dicarbonyl compounds

  13. The synthesis and molecular recognization of the polyamine transporter of hydrazine-modified diamine conjugates

    Institute of Scientific and Technical Information of China (English)

    Jun Jun Zhou; Hao Huang; Song Qiang Xie; Yu Xia Wang; Jin Zhao; Chao Jie Wang

    2008-01-01

    A series of four novel hydrazine-modified diamine conjugates (7a-b, 8a-b) were synthesized and evaluated for cytotoxicityagainst Melanoma B 16, α-difluoromethylornithine (DFMO)-treated B 16, spermidine (SPD)-treated B 16, Mouse leukemia L 1210and Hela cell lines. Both the DFMO-B 16 and SPD-B 16 experiments indicated that conjugates 7a-b and 8a-b could recognize thepolyamine transporter (PAT) and enter the cells in part or in whole via PAT, although they were not as efficient as the reference, 9-anthracenemethyl homospermidine (1).

  14. Hydrazine Blending and Storage Facility, Interim Response Action, Final Implementation Document for Decommissioning, Phase 1

    Science.gov (United States)

    1991-03-18

    PRIMARY OBJECTIVES OF THE IRA 2. SITE INVENTORY - TANKS, PIPING, BUILDINGS, ASBEST , DEBRIS, DRUMS 3. PLAN OF ACTION - TRANSFER OF UNTREATED WASTEWATER...Response Action (IRA) H at thte Hydrazine Blending and Storage Facility (HBSF) located at Rocky Mountain Arsenal (RMA) in Commerce City , Colorado. It was...LOCATION MAP Commerce CIty , Colorado 1A U) Cl)) zr LU .i I 0< 9< z (’ICM ..w co ai >. r 0) IC., Z C’) ________________0 W jl cor cliB destruction of

  15. Hydrogenation of liquid natural rubber via diimide reduction in hydrazine hydrate/hydrogen peroxide system

    Energy Technology Data Exchange (ETDEWEB)

    Yusof, Muhammad Jefri Mohd; Jamaluddin, Naharullah; Abdullah, Ibrahim; Yusoff, Siti Fairus M. [School of Chemical Sciences and Food Technology, Faculty of Science and Technology, Universiti Kebangsaan Malaysia, 43600 Bangi, Selangor (Malaysia)

    2015-09-25

    Liquid natural rubber (LNR) with molecular weight of lower than 10{sup 5} and shorter polymeric chain than natural rubber was prepared. LNR was then hydrogenated via diimide reduction by oxidation of hydrazine hydrate with hydrogen peroxide. The unsaturated units of the rubber were converted into saturated hydrocarbon to strengthen the backbone of the polymer so it was able to resist thermal degradation. The results indicated that hydrogenation degree of the product (HLNR) could be extended to 91.2% conversion under appropriate conditions. The hydrogenated LNR (HLNR) was characterized using Fourier-Transform Infrared (FTIR) and Nuclear Magnetic Resonance (NMR) spectroscopy. The physical characteristics of HLNR were analyzed with Termogravimetric Analysis (TGA)

  16. Alternatives to hydrazine in steam and hot water systems. Pt. 1

    Energy Technology Data Exchange (ETDEWEB)

    Hoehenberger, L.

    1989-04-01

    Ever since hydrazine was classified among the carcinogenics, users were confronted with a number of alternatives. The most common of these, i.e. ascorbate, carbohydrazide, diethyl hydroxylamine (DEHA), hydrochinine, hyposulfite, methyl ethylketoxime (MEKO), sulfite and tannines, are compared in a table with a view to their oxygen binding efficiency and other important characteristics. So far, there is no substitute with a simple reaction mechanism and optimum corrosion protection efficiency. Established physical methods are favoured for oxygen removal. Corrosion protection by passivation and inhibition are gone into. (orig.).

  17. Structure and Quantum Chemistry Study on Hexaacetyl D-Mannose Hydrazine

    Institute of Scientific and Technical Information of China (English)

    CAO Rui; LIU Xiao-Hong; CHENG Chang-Mei; WANG Ru-Ji; ZHAO Yu-Fen; WANG Lai-Xi

    2007-01-01

    Hexaacetyl D-mannose hydrazine is one type of important intermediates in saccharide chemistry. In this paper, its single crystal was obtained and furthermore, X-ray diffraction and quantum chemistry calculation were performed. It belongs to orthorhombic system, space group P212121, with a=16.267(3), b=19.263(3), c=7.1948(12)(A), Mr=446.41, Dc=1.315 g/cm3, V=2254.5(6)(A)3 and Z=4. Meanwhile, the experimental results also provide information for designing a kind of molecular switch based on the mannose nitrogenous derivatives.

  18. Sensitive amperometric determination of hydrazine using a carbon paste electrode modified with silver-doped zeolite L nanoparticles

    Indian Academy of Sciences (India)

    NEDA SALEK GILANI; SEYED NASER AZIZI; SHAHRAM GHASEMI

    2017-02-01

    Silver-loaded nanozeolite-L-modified carbon paste electrode (Ag/L–CPE) was used as a novel sensing platform for enhanced electrocatalytic oxidation and determination of hydrazine. Zeolite L nanoparticles were synthesized via hydrothermal approach and then characterized using various techniques such as X-ray diffraction (XRD), Fourier transform infrared (FTIR), scanning electronic microscopy (SEM) and Brunauer–Emmett–Teller (BET). Silver-exchanged nanozeolite L (Ag/L) was prepared and mixed with carbon paste to prepare the modified electrode. Cyclic voltammetry studies revealed the high performance of Ag/L–CPE for electrocatalytic oxidation of hydrazine. Two linear ranges were detected in the amperometric detection of hydrazine. The first range was from10 $\\mu$M to 0.4 mM with sensitivity of 103.13 $\\mu$A mM$^{−1}$ and the second one was from 0.4 to 4mM with sensitivity of 58.131 $\\mu$A mM$^{−1}$. The response time and detection limit ($S/N = 3$) of this sensor were determined to be 2 s and 1.5 $\\mu$M, respectively. The unique porous structure of nanozeolite L offers a promising catalyst support candidate for efficient electrochemical sensing of hydrazine. The sensor exhibited appreciable repeatability, reproducibility and stability, and was able to detect hydrazine in the presence of even 500-fold excess concentrations of interfering species. Also, the sensor was used to determine hydrazine concentration in water samples with satisfactory results.

  19. 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.

  20. Colorectal Anastomotic Leakage: New perspectives

    NARCIS (Netherlands)

    F. Daams (Freek)

    2014-01-01

    markdownabstract__Abstract__ This thesis provides new perspectives on colorectal anastomotic leakages. In both experimental and clinical studies, aspects of prevention, early identification, treatment and consequences of anastomotic leakage are discussed.

  1. 6 Common Cancers - Colorectal Cancer

    Science.gov (United States)

    ... Navigation Bar Home Current Issue Past Issues 6 Common Cancers - Colorectal Cancer Past Issues / Spring 2007 Table ... the United States, it is the third most common cancer in men and women. Caught early, it ...

  2. The development of a non-cryogenic nitrogen/oxygen supply system. [using hydrazine/water electrolysis

    Science.gov (United States)

    Greenough, B. M.; Mahan, R. E.

    1974-01-01

    A hydrazine/water electrolysis process system module design was fabricated and tested to demonstrate component and module performance. This module is capable of providing both the metabolic oxygen for crew needs and the oxygen and nitrogen for spacecraft leak makeup. The component designs evolved through previous R and D efforts, and were fabricated and tested individually and then were assembled into a complete module which was successfully tested for 1000 hours to demonstrate integration of the individual components. A survey was made of hydrazine sensor technology and a cell math model was derived.

  3. Ultrathin willow-like CuO nanoflakes as an efficient catalyst for electro-oxidation of hydrazine

    Science.gov (United States)

    Ma, Yuanyuan; Li, Hao; Wang, Rongfang; Wang, Hui; Lv, Weizhong; Ji, Shan

    2015-09-01

    In this paper, preparation of ultrathin willow-like CuO nanoflakes via a one-step process was reported. X-ray diffraction pattern showed the formation of monoclinic CuO crystal, which was also confirmed by result of high resolution transmission electron microscopy. Scanning electron microscopy showed that ultrathin willow-like CuO nanoflakes were formed. Catalytic testing indicated that the ultrathin willow-like CuO nanoflakes exhibited high electrocatalytic activity and durability toward the electro-oxidation of hydrazine in alkaline medium. The results suggested that the as-prepared CuO nanoflakes were potential electrode materials for hydrazine fuel cell.

  4. 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, histopathologic...... 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....

  5. 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....

  6. Diabetes Mellitus and Colorectal Neoplasia

    Science.gov (United States)

    Acevedo, Alejandro; Diaz, Yaritza; Perez, Cynthia M.; Garau, Maria; Baron, John

    2012-01-01

    Background Many studies have provided evidence for an association between obesity, physical inactivity, and western diet as risk factors for colorectal cancer (CRC). Few studies directly address the association between type 2 Diabetes Mellitus (DM) and the risk of colorectal lesions at specific anatomic locations. Methods 2,663 subjects with a previous history of adenoma(s) and removal of all current adenomas at study entry were followed for a mean time of three years across three different chemoprevention clinical trials. The primary endpoint was colorectal adenoma recurrence and number of lesions during the treatment phase; the secondary endpoints were presence of advanced colorectal neoplasia (CRN) and location of CRN. Using log linear regression, the effect of DM status on the relative risk (RR) of CRN recurrence, advanced CRN, and location of CRN was assessed. Results DM status was not significantly associated with incidence of colorectal adenomas, incidence of advanced colorectal lesions, or left-sided colorectal neoplastic lesions. Subjects with DM had a marginally increased risk of right-sided (p= 0.06) colorectal adenomas and a significant increased risk of multiple right-sided adenomas (p=0.03) in the unadjusted model; this association was not significant after adjusting for age and other potential confounders (RR=1.22, 95% CI: 0.85–1.76). Conclusion We did not observe a statistically significant increased risk in CRN recurrence for overall neoplasia, advanced neoplasia or location of neoplasia in individuals with DM compared to non-DM individuals. However, given the patterns observed in this investigation, future studies with longer follow-up time and longer DM exposure, incorporating objective measurements of type 2 DM might help elucidate the risk of CRN among individuals with DM. PMID:23560242

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

    Directory of Open Access Journals (Sweden)

    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.

  8. 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

  9. MicroRNA-96 promotes the proliferation of colorectal cancer cells and targets tumor protein p53 inducible nuclear protein 1, forkhead box protein O1 (FOXO1) and FOXO3a.

    Science.gov (United States)

    Gao, Feng; Wang, Wenhui

    2015-02-01

    MicroRNAs (miRNAs) are a conserved class of small, endogenous, non protein-coding RNA molecules that are capable of regulating gene expression at post-transcriptional levels and are involved in diverse cellular processes, including cancer pathogenesis. It has previously been reported that miRNA-96 (miR-96) is overexpressed in human colorectal cancer (CRC). However, the underlying mechanism of miR-96 regulation in CRC remains to be elucidated. In the present study, miR-96 was confirmed to be upregulated in CRC tissues by reverse transcription quantitative polymerase chain reaction. MTT assay, colony formation assay and cell cycle analysis revealed that miR-96 overexpression led to increased tumor cell viability, colony formation ability and cell cycle progression. By contrast, inhibition of miR-96 resulted in the suppression of cell proliferation. It was also demonstrated that miR-96 reduced the messenger RNA and protein expression levels of tumor protein p53 inducible nuclear protein 1 (TP53INP1), forkhead box protein O1 (FOXO1) and FOXO3a, which are closely associated with cell proliferation. A luciferase reporter assay indicated that miR-96 inhibited luciferase intensity controlled by the 3'UTRs of TP53INP1, FOXO1 and FOXO3a. In conclusion, the results of the present study demonstrated that miR-96 contributed to CRC cell growth and that TP53INP1, FOXO1 and FOXO3a were direct targets of miR-96, suggesting that miR-96 may have the potential to be used in the development of miRNA‑based therapies for CRC patients.

  10. Morin Inhibits Proliferation of SW480 Colorectal Cancer Cells by Inducing Apoptosis Mediated by Reactive Oxygen Species Formation and Uncoupling of Warburg Effect

    Directory of Open Access Journals (Sweden)

    Thomas Sithara

    2017-09-01

    Full Text Available The study under investigation focuses on in vitro antiproliferative efficacy of the flavonoid morin and the mechanisms by which it inhibits the growth of colon cancer using SW480 colon cancer cells with emphasis on Warburg effect. It was found that the cell proliferation was significantly inhibited by morin in a dose and time dependent manner. Morin induced apoptosis that was correlated with increased levels of reactive oxygen species formation and loss of mitochondrial membrane potential of the cells. In addition, an increase in cleaved PARP, cleaved caspase 3, cleaved caspase 8, cleaved caspase 9 and Bax as well as a decrease in Bcl 2 was observed, indicating morin is inducing both intrinsic as well as extrinsic pathway of apoptosis. This was further confirmed by using downstream caspase 3 inhibitor which indicated that caspase 3 inhibition reduces morin induced cell death. Moreover, the impact of morin on over all energy status when determined in terms of total cellular ATP level showed a decline with low level of glucose uptake and Glut1 expression. The results indicate that morin exerts antiproliferative activity by inducing apoptosis and by reducing Warburg effect in the evaluated cell lines and provide preliminary evidence for its anticancer activity.

  11. Expression of tumour necrosis factor-related apoptosis-inducing ligand death receptors in sporadic and hereditary colorectal tumours : Potential targets for apoptosis induction

    NARCIS (Netherlands)

    Koornstra, JJ; Jalving, M; Rijcken, FEM; Westra, Jantine; Zwart, N; Hollema, H; de Vries, EGE; Hofstra, RWM; Plukker, JTM; de Jong, S; Kleibeuker, JH

    2005-01-01

    Tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) and antibodies against TRAIL receptors death receptor 4 (DR4) and death receptor 5 (DR5) are under investigation for cancer therapy. To study the potential application of these agents, the expression of DR4 and DR5 were studied immunoh

  12. Arctigenin Inhibits Lung Metastasis of Colorectal Cancer by Regulating Cell Viability and Metastatic Phenotypes

    OpenAIRE

    2016-01-01

    Arctigenin (ARC) has been shown to have an anti-cancer effect in various cell types and tissues. However, there have been no studies concerning metastatic colorectal cancer (CRC). In this study, we investigated the anti-metastatic properties of ARC on colorectal metastasis and present a potential candidate drug. ARC induced cell cycle arrest and apoptosis in CT26 cells through the intrinsic apoptotic pathway via MAPKs signaling. In several metastatic phenotypes, ARC controlled epithelial-mese...

  13. Crystal structures of nitrato-(2-[2-(1-pyridine-2-ylethylidene)hydrazine]-1,3-benzothiazolo) aquacopper and chloro-(2-[2-phenyl(pyridine-2-ylethylidene)hydrazine]-1,3-benzothiazolo) copper

    Energy Technology Data Exchange (ETDEWEB)

    Chumakov, Yu. M. [Academy of Sciences of Moldova, Institute of Applied Physics (Moldova, Republic of); Paholnitcaia, A. Yu. [State University of Moldova (Moldova, Republic of); Petrenko, P. A. [Academy of Sciences of Moldova, Institute of Applied Physics (Moldova, Republic of); Tsapkov, V. I., E-mail: vtsapkov@gmail.com [State University of Moldova (Moldova, Republic of); Poirier, D. [Centre Hospitalier Universitaire de Quebec (Canada); Gulea, A. P. [State University of Moldova (Moldova, Republic of)

    2015-01-15

    Two crystal modifications of nitrato-(2-[2-(1-pyridine-2-ylethylidene)hydrazine]-1,3-benzothiazolo) aquacopper (I and II) and two modifications of chloro-(2-[2-phenyl(pyridine-2-ylethylidene)hydrazine]-1,3-benzothiazolo) copper (III and IV) have been synthesized and studied by X-ray diffraction. In structures I and II, the copper atoms coordinate a monodeprotonated molecule of the organic ligand, nitrate ions, and a water molecule. In crystals of I, the complexes are monomeric, whereas complexes II are linked via nitrate ions to form polymeric chains. In both structures the coordination polyhedron of the copper atom can be described as a distorted tetragonal bipyramid—(4 + 1 + 1) in I and (4 + 2) in II. These coordination polyherdra have different compositions. In structures III and IV, the metal atoms coordinate a monodeprotonated (2-[2-phenyl(pyridine-2-ylethylidene)hydrazine]-1,3-benzothiazole molecule and chloride ions. In III the complex-forming ion has square-planar coordination geometry, whereas structure IV consists of centrosymmetric dimers with two bridging chlorine atoms. It was found that nitrato-(2-[2-(1-pyridine-2-ylethylidene)hydrazine]-1,3-benzothiazolo) aquacopper possesses antitumor activity.

  14. Sol-gel process preparation and evaluation of the analytical performances of an hydrazine specific chemical sensor; Preparation par procede sol-gel et evaluation des performances analytiques d`un capteur chimique specifique de l`hydrazine

    Energy Technology Data Exchange (ETDEWEB)

    Gojon, C

    1996-12-01

    The realisation of optical fibers active chemical collector to analyze hydrazine in line, in the spent fuel reprocessing process is the subject of this work. The p.dimethyl-amino-benzaldehyde has been chosen as reagent for its chemical and optical properties. 186 refs.

  15. Crystal structures of nitrato-{2-[2-(1-pyridine-2-ylethylidene)hydrazine]-1,3-benzothiazolo}aquacopper and chloro-{2-[2-phenyl(pyridine-2-ylethylidene)hydrazine]-1,3-benzothiazolo}copper

    Science.gov (United States)

    Chumakov, Yu. M.; Paholnitcaia, A. Yu.; Petrenko, P. A.; Tsapkov, V. I.; Poirier, D.; Gulea, A. P.

    2015-01-01

    Two crystal modifications of nitrato-{2-[2-(1-pyridine-2-ylethylidene)hydrazine]-1,3-benzothiazolo}aquacopper ( I and II) and two modifications of chloro-{2-[2-phenyl(pyridine-2-ylethylidene)hydrazine]-1,3-benzothiazolo}copper ( III and IV) have been synthesized and studied by X-ray diffraction. In structures I and II, the copper atoms coordinate a monodeprotonated molecule of the organic ligand, nitrate ions, and a water molecule. In crystals of I, the complexes are monomeric, whereas complexes II are linked via nitrate ions to form polymeric chains. In both structures the coordination polyhedron of the copper atom can be described as a distorted tetragonal bipyramid—(4 + 1 + 1) in I and (4 + 2) in II. These coordination polyherdra have different compositions. In structures III and IV, the metal atoms coordinate a monodeprotonated {2-[2-phenyl(pyridine-2-ylethylidene)hydrazine]-1,3-benzothiazole molecule and chloride ions. In III the complex-forming ion has square-planar coordination geometry, whereas structure IV consists of centrosymmetric dimers with two bridging chlorine atoms. It was found that nitrato-{2-[2-(1-pyridine-2-ylethylidene)hydrazine]-1,3-benzothiazolo}aquacopper possesses antitumor activity.

  16. Advances in pediatric colorectal surgical techniques.

    NARCIS (Netherlands)

    Rangel, S.J.; Blaauw, I. de

    2010-01-01

    The operative management of pediatric colorectal diseases has improved significantly in recent years through the development of innovative approaches for operative exposure and a better understanding of colorectal anatomy. Advances in transanal and minimal access techniques have formed the

  17. Genetic Testing for Hereditary Colorectal Cancer

    Science.gov (United States)

    ... Emails Have You or a Family Member Had Colorectal (Colon) Cancer? Language: English Español (Spanish) Recommend on Facebook Tweet ... cancer can make you more likely to get colorectal cancer yourself. If you have close family members with ...

  18. Loss of heterozygosity in colorectal cancer

    African Journals Online (AJOL)

    STORAGESEVER

    2009-12-29

    Dec 29, 2009 ... adenocarcinoma (Grady, 2005). CRC occurs ... risk of getting colorectal cancer increases with age. ..... pancreas, ovarian, lung and liver tumours (Wan et al.,. 2006). Wan et ... independent prognostic factor of colorectal cancer.

  19. A novel class I histone deacetylase inhibitor, I-7ab, induces apoptosis and arrests cell cycle progression in human colorectal cancer cells.

    Science.gov (United States)

    Yang, Liyan; Liang, Qiannan; Shen, Ke; Ma, Li; An, Na; Deng, Weiping; Fei, Zhewei; Liu, Jianwen

    2015-04-01

    Epigenetic mutations are closely associated with human diseases, especially cancers. Among them, dysregulations of histone deacetylases (HDACs) are commonly observed in human cancers. Recent years, HDAC inhibitors have been identified as promising anticancer agents; several HDAC inhibitors have been applied in clinical practice. In this study, we synthesized a novel N-hydroxyacrylamide-derived HDAC inhibitor, I-7ab, and examined its antitumor activity. Our investigations demonstrated that I-7ab exerted cytotoxicity toward and inhibited the growth of human cancer cell lines at micromolar concentrations. Among tested cells, HCT116 was the most sensitive one to the treatment of I-7ab. However, I-7ab displayed far less cytotoxicity in human normal cells. In HCT116 cells, I-7ab inhibited the expression of class I HDACs, especially that of HDAC3, and suppressed EGFR signaling pathway. With respect to the cytotoxic effect of I-7ab, it induced apoptosis via increasing the Bax/Bcl-2 ratio and suppressing the translocation of NF-κB. Other than inducing apoptosis, I-7ab inhibited the expression of cyclin B1 and thereby arrests cell cycle progression at G2/M phase. Further analyses revealed potential role of p53 and p21 in I-7ab-induced apoptosis and cell cycle arrest. According to our findings, I-7ab may serve as a lead compound for potential antitumor drugs.

  20. Investigation of the direct and indirect electrochemical oxidation of hydrazine in nitric acid medium on platinum; Etude de l`oxydation electrochimique directe et indirecte de l`hydrazine en milieu acide nitrique sur platine

    Energy Technology Data Exchange (ETDEWEB)

    Cames, B

    1997-12-31

    In nuclear fuel processing by the PUREX process, the purification of plutonium in nitric acid medium requires the oxidation of Pu(III) to Pu(IV), and of hydrazinium nitrate to nitrogen. The study helped to characterize the electrochemical behavior of the oxidation of hydrazinium nitrate and the reduction of nitric acid to nitrous acid, a compound which can chemically oxidize hydrazinium nitrate and Pu(III). Electro-analytical studies on polycrystalline platinum showed that hydrazine is oxidized in two potential zones, which depend on the surface texture of the platinum anode. Electrolysis in separate compartments, carried out in medium-acid media (2 and 4 mo/l) in the potential zone where these processes take place, showed that, at 0.9 V/ECS, the hydrazine oxidation reactions involved are: a four-electron process (75 %) with nitrogen formation and a one-electron process (25 %) with formation of nitrogen and ammonium ion. By contrast, electrolysis carried out at 0.65 V/ECS (with reactivation of the electrode at - 0.2 V/ECS to remove the poison from the platinum) allowed the selective oxidation of hydrazine to nitrogen by the four-electron reaction. Nitric acid can only be reduced to nitrous acid in the absence of hydrazine. For medium-acid media ({<=} 6 mol/l), this reaction takes place at potentials below - 0.2 V/ECS. However, the production rate of nitrous acid (partial order 0 with respect to nitric acid) is very low compared with the values obtained for strongly-acid media (6 to 10 mol/l) at the potential of - 0.1 V/ECS. Note that, in concentrated nitric medium, the selectivity of the reduction reaction is 47 to 85 % for nitrous acid, depending on the nitric acid concentration (6 to 10 mol/l) and the potential imposed (- 0.1 {<=} E {<=} 0.6 V/ECS). A kinetic study helped to determine the hydrazine oxidation rates as a function of the operating conditions. In all cases, the reaction rate is of partial order 0 with respect to hydrazine. These studies accordingly

  1. Adsorption of hydrazine on the perfect and defective copper (111) surface: A dispersion-corrected DFT study

    NARCIS (Netherlands)

    Tafreshi, Saeedeh S.; Roldan, Alberto; Dzade, Nelson Y.; de Leeuw, Nora H.

    2014-01-01

    We have investigated the adsorption of hydrazine (N2H4) on perfect and defect-containing copper (111) surfaces by first-principles calculations. The long-range interactions are included in the geometry optimization through the application of the generalised gradient approximation with dispersion cor

  2. In situ synthesis of ceria nanoparticles in the ordered mesoporous carbon as a novel electrochemical sensor for the determination of hydrazine

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Yue [College of Chemistry, Nankai University, 94 WeiJin Road, Tianjin 300071 (China); Li, Yijun, E-mail: yijunli@nankai.edu.cn [Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Tianjin 300071 (China); College of Chemistry, Nankai University, 94 WeiJin Road, Tianjin 300071 (China); He, Xiwen [College of Chemistry, Nankai University, 94 WeiJin Road, Tianjin 300071 (China)

    2014-03-01

    Highlights: • CeO{sub 2}–OMC composites were prepared via a hydrothermal method. • CeO{sub 2}–OMC had electrocatalytic ability to oxidation of hydrazine. • The sensor had high sensitivity, excellent stability and reproducibility. • The sensor was successfully employed to detect hydrazine in real water samples. - Abstract: A novel ceria (CeO{sub 2})–ordered mesoporous carbon (OMC) modified electrode for the sensitive amperometric determination of hydrazine was reported. CeO{sub 2}–OMC composites were synthesized via a hydrothermal method at a relatively low temperature (180 °C) and characterized by scanning electron microscopy (SEM), transmission electron microcopy (TEM), X-ray photoelectron spectroscopy (XPS) and X-ray diffraction (XRD). The CeO{sub 2}–OMC modified glassy carbon electrode was characterized by electrochemical impedance spectroscopy (EIS) and cyclic voltammetry (CV) and indicated good electrocatalytic effect to the oxidation of hydrazine. Under the optimized conditions, the present sensor could be used to measure hydrazine in wide linear range from 40 nM to 192 μM (R{sup 2} = 0.999) with a low detection limit of 12 nM (S/N = 3). Additionally, the sensor has been successfully applied to detect hydrazine in real water samples and the recoveries were between 98.2% and 105.6%. Eventually, the sensor exhibited an excellent stability and reproducibility as a promising method for determination of hydrazine.

  3. Effect of auricular acupuncture on visceral pain induced by colorectal distension in rats%耳针对结直肠扩张导致大鼠内脏痛的影响

    Institute of Scientific and Technical Information of China (English)

    胡莎莎; 李晗; 王茵萍

    2013-01-01

    目的 研究耳针对结直肠扩张(CRD)所造成大鼠内脏痛的影响.方法 29只SD大鼠随机分为空白对照组(A组,7只)、模型组(B组,7只)、耳针组(C组,8只)和假针刺组(D组,7只).连续记录大鼠CRD前后、干预期及干预后各30 min的肌电图(EMG)和心率变异性(HRV),采用荧光定量PCR观察结肠中5-羟色胺1A(5-HTIA)受体mRNA的表达.结果 CRD后,B、C、D组EMG均较A组显著升高(P<0.05),但HRV与扩张前比较无统计学差异(P>0.05).C组EMG和5-HT1A受体mRNA表达较B组、D组明显降低(P<0.05).结论 耳针可有效改善CRD导致的大鼠内脏痛.这种调节作用可能与5-HT递质受体系统有关.%Objective To investigate the effect of auricular acupuncture on the visceral pain induced by colorectal distension(CRD) in rats.Methods Twenty-nine SD rats were randomly divided into four groups of A (blank control,7 rats),B (CRD model,7 rats),C (intervened with auricular acupuncture,8 rats) and D(sham acupuncture,7 rats).The electromyography(EMG) and heart rate variability(HRV) were continuously recorded each for 30 min before and after CRD and during and after intervention.The mRNA expression of 5-hydroxytryptamine1A (5-HT1A) receptor in the colon tissues was detected by fluorescent quantitative PCR.Results After CRD,EMG in groups of B,C and D was significantly higher than that in group A(P<0.05),but HRV was not markedly changed,compared with baseline (P>0.05).The mRNA expression of 5-HT1A receptor and EMG in group C were lower than those in groups of B and D (P<0.05).Conclusion Auricular acupuncture can effectively improve visceral pain induced by CRD in rats,which may be related to 5-HT receptor system.

  4. Association of Fusobacterium nucleatum with immunity and molecular alterations in colorectal cancer.

    Science.gov (United States)

    Nosho, Katsuhiko; Sukawa, Yasutaka; Adachi, Yasushi; Ito, Miki; Mitsuhashi, Kei; Kurihara, Hiroyoshi; Kanno, Shinichi; Yamamoto, Itaru; Ishigami, Keisuke; Igarashi, Hisayoshi; Maruyama, Reo; Imai, Kohzoh; Yamamoto, Hiroyuki; Shinomura, Yasuhisa

    2016-01-14

    The human intestinal microbiome plays a major role in human health and diseases, including colorectal cancer. Colorectal carcinogenesis represents a heterogeneous process with a differing set of somatic molecular alterations, influenced by diet, environmental and microbial exposures, and host immunity. Fusobacterium species are part of the human oral and intestinal microbiota. Metagenomic analyses have shown an enrichment of Fusobacterium nucleatum (F. nucleatum) in colorectal carcinoma tissue. Using 511 colorectal carcinomas from Japanese patients, we assessed the presence of F. nucleatum. Our results showed that the frequency of F. nucleatum positivity in the Japanese colorectal cancer was 8.6% (44/511), which was lower than that in United States cohort studies (13%). Similar to the United States studies, F. nucleatum positivity in Japanese colorectal cancers was significantly associated with microsatellite instability (MSI)-high status. Regarding the immune response in colorectal cancer, high levels of infiltrating T-cell subsets (i.e., CD3+, CD8+, CD45RO+, and FOXP3+ cells) have been associated with better patient prognosis. There is also evidence to indicate that molecular features of colorectal cancer, especially MSI, influence T-cell-mediated adaptive immunity. Concerning the association between the gut microbiome and immunity, F. nucleatum has been shown to expand myeloid-derived immune cells, which inhibit T-cell proliferation and induce T-cell apoptosis in colorectal cancer. This finding indicates that F. nucleatum possesses immunosuppressive activities by inhibiting human T-cell responses. Certain microRNAs are induced during the macrophage inflammatory response and have the ability to regulate host-cell responses to pathogens. MicroRNA-21 increases the levels of IL-10 and prostaglandin E2, which suppress antitumor T-cell-mediated adaptive immunity through the inhibition of the antigen-presenting capacities of dendritic cells and T-cell proliferation in

  5. Identification of a new cyathane diterpene that induces mitochondrial and autophagy-dependent apoptosis and shows a potent in vivo anti-colorectal cancer activity.

    Science.gov (United States)

    He, Luwei; Han, Junjie; Li, Baowei; Huang, Li; Ma, Ke; Chen, Quan; Liu, Xinzhong; Bao, Li; Liu, Hongwei

    2016-03-23

    Diterpenes has been reported to possess multiple bioactivities consisting of anti-microbial and anti-inflammatory properties. This study reveals a new cyathane-type diterpene (cyathin Q) from the culture of the fungus Cyathus africanus by bioactivity-guided separation. The structure of cyathin Q was determined based on spectroscopic measurements (NMR and MS). The bioactivity evaluation shows that cyathin Q has a strong anticancer activity against HCT116 cells and Bax-deficient HCT116 in vitro and in vivo. This compound induced hallmarks of apoptotic events in HCT116 cells, including caspase activation, cytochrome c release, poly (ADP-ribose) polymerase (PARP) cleavage, and depolarization of the mitochondrial inner transmembrane potential. This process is accompanied with the increased mitochondrial ROS, down-regulation of Bcl-2 protein, and up-regulation of Bim protein. We also observed the cleavage of autophagy-related protein ATG5 in cyathin Q-induced apoptosis. Taken together, our study identified a new fungal diterpene that exhibited anticancer activity via induction of mitochondria and autophagy-dependent apoptosis in HCT116 cells.

  6. CYP2E1 mediated isoniazid-induced hepatotoxicity in rats

    Institute of Scientific and Technical Information of China (English)

    Jiang YUE; Ren-xiu PENG; Jing YANG; Rui KONG; Juan LIU

    2004-01-01

    AIM: To investigate the role of CYP2E1 in isoniazid (INH)-induced hepatotoxicity and the influence of rifampicin (RFP) on INH-induced liver injury. METHODS: Rats were treated with INH alone (100 mg/kg, ip) or co-administered with RFP (100 mg/kg, ig) for 10 d and 21 d. Hepatotoxicity was assayed by plasma enzymes (sALT, sAST) and histopathological examinations. Hepatic CYP2E1 activity was measured by aniline hydroxylase (ANH), and CYP2E1 mRNA expression was determined by RT-PCR. Plasma hydrazine concentration was determined by RP-HPLC.RESULTS: For a 10 d INH-treatment, hepatic CYP2E1 level was increased to 3.7-fold over the control; liver impairment appeared after 21 d treatment, while CYP2E1 and plasma hydrazine were, respectively, increased to 4.6-fold and 1.7-fold. However, in INH-RFP group for 10 d, CYP2E1 and plasma hydrazine were, respectively,decreased by 13 % and 18 % over INH group; similarly, hepatic injury is equal to INH group appeared after 21 d,and CYP2E1 was further decreased by 26 %. Correlation analysis showed that sALT had a positive correlation with plasma hydrazine and with CYP2E1 activity; CYP2E1 activity was also markedly correlated with plasma hydrazine.And compared with control, there is no difference in changes of CYP2E1 mRNA expression in INH and INH-RFP treatment for 21 d. CONCLUSION: The metabolite of INH, hydrazine, plays an important role in INH-induced hepatotoxicity in rats. The induction of CYP2E1 by hydrazine is involved in the hepatotoxicity of INH. RFP does not exacerbate INH-induced hepatotoxicity in short term, which relates to down-regulation of CYP2E1.

  7. A blended knowledge translation initiative to improve colorectal cancer staging [ISRCTN56824239

    Directory of Open Access Journals (Sweden)

    Ryan David P

    2006-01-01

    Full Text Available Abstract Background A significant gap has been documented between best practice and the actual practice of surgery. Our group identified that colorectal cancer staging in Ontario was suboptimal and subsequently developed a knowledge translation strategy using the principles of social marketing and the influence of expert and local opinion leaders for colorectal cancer. Methods/Design Opinion leaders were identified using the Hiss methodology. Hospitals in Ontario were cluster-randomized to one of two intervention arms. Both groups were exposed to a formal continuing medical education session given by the expert opinion leader for colorectal cancer. In the treatment group the local Opinion Leader for colorectal cancer was detailed by the expert opinion leader for colorectal cancer and received a toolkit. Forty-two centres agreed to have the expert opinion leader for colorectal cancer come and give a formal continuing medical education session that lasted between 50 minutes and 4 hours. No centres refused the intervention. These sessions were generally well attended by most surgeons, pathologists and other health care professionals at each centre. In addition all but one of the local opinion leaders for colorectal cancer met with the expert opinion leader for colorectal cancer for the academic detailing session that lasted between 15 and 30 minutes. Discussion We have enacted a unique study that has attempted to induce practice change among surgeons and pathologists using an adapted social marketing model that utilized the influence of both expert and local opinion leaders for colorectal cancer in a large geographic area with diverse practice settings.

  8. Activation of AMP-Activated Protein Kinase α and Extracelluar Signal-Regulated Kinase Mediates CB-PIC-Induced Apoptosis in Hypoxic SW620 Colorectal Cancer Cells.

    Science.gov (United States)

    Cho, Sung-Yun; Lee, Hyo-Jeong; Lee, Hyo-Jung; Jung, Deok-Beom; Kim, Hyunseok; Sohn, Eun Jung; Kim, Bonglee; Jung, Ji Hoon; Kwon, Byoung-Mog; Kim, Sung-Hoon

    2013-01-01

    Here, antitumor mechanism of cinnamaldehyde derivative CB-PIC was elucidated in human SW620 colon cancer cells. CB-PIC significantly exerted cytotoxicity, increased sub-G1 accumulation, and cleaved PARP with apoptotic features, while it enhanced the phosphorylation of AMPK alpha and ACC as well as activated the ERK in hypoxic SW620 cells. Furthermore, CB-PIC suppressed the expression of HIF1 alpha, Akt, and mTOR and activated the AMPK phosphorylation in hypoxic SW620 cells. Conversely, silencing of AMPK α blocked PARP cleavage and ERK activation induced by CB-PIC, while ERK inhibitor PD 98059 attenuated the phosphorylation of AMPK α in hypoxic SW620 cells, implying cross-talk between ERK and AMPK α . Furthermore, cotreatment of CB-PIC and metformin enhanced the inhibition of HIF1 α and Akt/mTOR and the activation of AMPK α and pACC in hypoxic SW620 cells. In addition, CB-PIC suppressed the growth of SW620 cells inoculated in BALB/c athymic nude mice, and immunohistochemistry revealed that CB-PIC treatment attenuated the expression of Ki-67, CD34, and CAIX and increased the expression of pAMPK α in CB-PIC-treated group. Interestingly, CP-PIC showed better antitumor activity in SW620 colon cancer cells under hypoxia than under normoxia, since it may be applied to chemoresistance. Overall, our findings suggest that activation of AMPK α and ERK mediates CB-PIC-induced apoptosis in hypoxic SW620 colon cancer cells.

  9. Associations between NBS1 Polymorphisms and Colorectal Cancer in Chinese Population.

    Science.gov (United States)

    Li, Jing-Tao; Zhong, Bao-Yuan; Xu, Hui-Hui; Qiao, Sheng-Yan; Wang, Gui; Huang, Jing; Fan, Hui-Zhen; Zhao, Hong-Chuan

    2015-01-01

    As the central protein of the double strand breaks (DSB)-induced DNA repair pathway, NBS1 participates in detecting the DSBs and plays an essential role in maintaining genomic stability. Single nucleotide polymorphisms (SNPs) in NBS1 gene were commonly tested that associated with the susceptibility to multiple cancers, but the results remained controversial. Thus, we conducted two independent hospital-based case-control studies comprising 1,072 colorectal cancer patients and 1,263 controls to evaluate the association between four NBS1 SNPs and colorectal cancer risk. The result showed that rs2735383C/G polymorphism in the 3'-untranslated region (UTR) of NBS1 was significantly associated with risk of colorectal cancer using logistic regression (Ptranscriptional activity and expression level. In conclusion, current evidence suggests that the rs2735383C/G polymorphism might contribute to the risk for colorectal cancer.

  10. Colorectal cancer screening

    Directory of Open Access Journals (Sweden)

    Almeida Frederico Ferreira Novaes de

    2000-01-01

    Full Text Available Colorectal cancer (CRC is the third most common cancer in the world, and mortality has remained the same for the past 50 years, despite advances in diagnosis and treatment. Because significant numbers of patients present with advanced or incurable stages, patients with pre-malignant lesions (adenomatous polyps that occur as result of genetic inheritance or age should be screened, and patients with long-standing inflammatory bowel disease should undergo surveillance. There are different risk groups for CRC, as well as different screening strategies. It remains to be determined which screening protocol is the most cost-effective for each risk catagory. The objective of screening is to reduce morbidity and mortality in a target population. The purpose of this review is to analyze the results of the published CRC screening studies, with regard to the measured reduction of morbidity and mortality, due to CRC in the studied populations, following various screening procedures. The main screening techniques, used in combination or alone, include fecal occult blood tests, flexible sigmoidoscopy, and colonoscopy. Evidence from the published literature on screening methods for specific risk groups is scanty and frequently does not arise from controlled studies. Nevertheless, data from these studies, combined with recent advances in molecular genetics, certainly lead the way to greater efficacy and lower cost of CRC screening.

  11. Diagnostic Ultrasound in Colorectal Cancer

    DEFF Research Database (Denmark)

    Rafaelsen, Søren Rafael

    2014-01-01

    SUMMARYBackground and purpose Colorectal cancer is a common disease in Denmark with considerable morbidity and mortality. Although survival in recent years has improved, Denmark still has the lowest 5-year survival compared to the other Nordic countries. The treatment of patients depends on local...... 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...... with the resulting pathological examination in relation to differentiating benign from malignant polyps and determining tumour stage and lymph node status. In this context we also performed an observer comparison using both TRUS and MRI. Consistency of tumour outgrowth of rectal cancer rated by TRUS and MRI...

  12. Chemical Carcinogen (Hydrazine et al.) Induced Carcinogenesis of Human Diploid Cells in Vitro

    Science.gov (United States)

    1982-09-07

    Chsaactariaane a/lthe Transformed C4110. essential amino acids. IX euenstial amino acida.,USAq 2.0 mM giutamine, IX vitamina , 0.2% sodium Taumor omnk in...subcutaneous injection of *&mino acids. 2.0 mM glusamine. IX vitamina , SX 10’ carcinogen-treazed or control cells ssa. 0.2% sodium bicarbonate. S iAg/ml

  13. Chemical Carcinogen (Hydrazine et al.) Induced Carcinogenesis of Human Diploid Fibroblasts in vitro.

    Science.gov (United States)

    1985-06-12

    coumarin; QU, quercetin; ISO, isoquinoline; I-Me-NA, l-methylnicotinamide; HMBA, hexamethylene bisacetamide; CAFF, caffeine; PRIM, primycin . The cell...of these anti- cells after PD2o biotics (nos 4,5) and of the antibiotic primycin I PD1 0.7AM MNNG alone 185 t 18 (2)a " (no.13) occurs at much lower...Pharmaceuticals 38, 168-181. % (Piscataway, NJ) and Primycin from Chinoin Ltd [121 Amery, W.K. and Butterworth, B.S. (1983) Int. J. (Budapest) through the

  14. Chemical Carcinogen (Hydrazine et al.) Induced Carcinogenesis of Human Diploid Fibroblasts in vitro.

    Science.gov (United States)

    1983-12-29

    determined as " .%. a measure of the growth phase (Cristofalo aid Sharf , 1973). The cultures were maintained in complete growth medium com- posed of... Sharf , 1973) dropped to ɘ.1%. At point R . [. (Fig. 1), the 0M medium was replaced with CM (Milo et al., ... .[-:1981), and IN was added to the CM. After...1982). Ann. N.Y. Acad. Sci. 207, 19-27. Cristofalo, V., and Sharf , B. (1973). Exp. Cell Res. 76, 419-427. Dedman, F. R., Welsh, M. J., and Means, A

  15. Suppression of colorectal tumor growth by regulated survivin targeting.

    Science.gov (United States)

    Li, Binghua; Fan, Junkai; Liu, Xinran; Qi, Rong; Bo, Linan; Gu, Jinfa; Qian, Cheng; Liu, Xinyuan

    2006-12-01

    A major goal in cancer gene therapy is to develop efficient gene transfer protocols that allow tissue-specific and tightly regulated expression of therapeutic genes. The ideal vector should efficiently transduce cancer cells with minimal toxicity on normal tissues and persistently express foreign genes. One of the most promising regulatory systems is the mifepristone/RU486-regulated system, which has much lower basal transcriptional activity and high inducibility. In this work, we modified this system by incorporating a cancer-specific promoter, the human telomerase reverse transcriptase (hTERT) promoter. By utilizing hTERT promoter to control the regulator, RU486 could specifically induce the expression of foreign genes in cancer cells but not in normal cells. In the context of this system, a dominant negative mutant of survivin (surDN) was controllably expressed in colorectal tumor cells. The surDN expression induced by RU486 showed a dosage- and time-dependent pattern. Regulated expression of surDN caused caspase-dependent apoptosis in colorectal tumor cells but had little effect on normal cells. Analysis of cell viability showed that RU486-induced expression of surDN suppressed colorectal tumor cell growth and had synergic effect in combination with chemotherapeutic agents. The potential of this system in cancer therapy was evaluated in experimental animals. Tumor xenograft models were established in nude mice with colorectal tumor cells, and RU486 was intraperitoneally administered. The results showed that conditional expression of surDN efficiently inhibited tumor growth in vivo and prolonged the life of tumor-burdened mice. Synergized with the chemotherapeutic drug cisplatin, regulated surDN expression completely suppressed tumor growth. These results indicated that this modified RU486-regulated system could be useful in cancer-targeting therapy.

  16. 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.

  17. Liquid phase synthesis: preparation of co microspheres by hydrazine reducing method

    Science.gov (United States)

    Deng, Y.; Lu, Z. Q.; Xie, F.; Liang, H.; Wang, Y. J.; Du, X. H.

    2017-01-01

    The study synthesizes Co microspheres with perfect spherical shape by use hydrazine hydrate as reducing agent to reduce CoCl2 in alkaline conditions at room temperature, the influence of NaOH addition amount on crystal morphology and structure of cobalt particle were studied. The results show that, under the condition of concentration of NaOH, 0.030g ml-1 and having ethylene glycol as solvent, are the best choice to synthesize Co microspheres, and the grain is smaller, suitable for industrial production. At the condition of less amount of NaOH, cobalt particle's surface is smooth spherical, and with the increase of NaOH, particles will deviate from the spherical morphology and the surface become rough. The first section in your paper

  18. A simple hydrazine based molecule for selective detection of Fluoride ion in DMSO

    Indian Academy of Sciences (India)

    ADDITI ROY CHOWDHURY; PRIYABRATA BANERJEE

    2017-04-01

    A newly synthesized hydrazine-functionalized Schiff base chemoreceptor [N¹N³−bis(4-cyanobenzylidene) isophthalahydrazide], NBCBIH has been prepared and successfully utilized for selective detection of Fluoride ion. Herein, NH and C=N-like functional units have been incorporated which providebetter colorimetric response compared to systems where such kind of units are absent. On exposure to F⁻, NBCBIH turns from almost colorless to yellow. The recognition is well-supported by UV-Vis, fluorescence and ¹H-NMR in DMSO. The fluorescence quenching is well-explained by photoinduced electron transfer mechanism (PET). The limit of detection of F− with NBCBIH is 0.7 × 10⁻⁴M.

  19. Theoretical Studies of Structure, Spectroscopy, and Properties of a New Hydrazine Derivative

    Directory of Open Access Journals (Sweden)

    Hajar Sahebalzamani

    2013-01-01

    Full Text Available We will report a combined experimental and theoretical study on molecular structure, vibrational spectra, and energies of (E-1-(2,4-dinitrophenyl-2-[(4-methylphenylmethylidene]hydrazine (1. The molecular geometry and vibrational frequencies and energies in the ground state are calculated by using HF and DFT levels of theory with 6-311G basis sets. The calculated HOMO and LUMO energies also confirm that charge transfer occurs within the molecule. The harmonic vibrational frequencies were calculated, and the scaled values have been compared with experimental FTIR and FT-Raman spectra. The observed and the calculated frequencies are found to be in good agreement. The experimental spectra also coincide satisfactorily with those of theoretically constructed bar-type spectrograms.

  20. Cubic Copper Hexacyanoferrates Nanoparticles: Facile Template-Free Deposition and Electrocatalytic Sensing Towards Hydrazine

    Directory of Open Access Journals (Sweden)

    Xingxing Wang

    2011-01-01

    Full Text Available Cubic copper hexacyanoferrate (CuHCF nanoparticles prepared via electrolytic deposition are presented with their morphology and crystalline structure characterized with SEM and XRD. The advantage of this methodology is that it allows the fabrication of uniform cubic nanoparticles with permeable structures onto the desired underlying electrode substrate. It was observed that the CuHCF film acts as a permeable membrane for cations such as K+, Na+, Li+, and NH4+ with a selection order of K+> Li+>NH4+> Na+. Furthermore, the analytical utility of these cubic-like CuHCF morphologies supported on a glassy carbon electrode was evaluated towards the electrochemical oxidation of hydrazine which was found to exhibit a linear response over the range 66 M to 17 mM with a detection limit corresponding to 16.5 M.

  1. Superior supercapacitor electrode material from hydrazine hydrate modified porous polyacrylonitrile fiber

    Science.gov (United States)

    Li, Ying; Lu, Chunxiang; Wang, Junzhong; Yan, Hua; Zhang, Shouchun

    2016-03-01

    A hierarchical porous carbon fiber with high nitrogen doping was fabricated for high-performance supercapacitor. For the purpose of high nitrogen retention, the porous polyacrylonitrile fiber was treated by hydrazine hydrate, and then underwent pre-oxidation, carbonization, and activation in sequence. The resulted material exhibited high nitrogen content of 7.82 at.%, large specific surface area of 1963.3m2 g-1, total pore volume of 1.523cm3 g-1, and the pores with size range of 1-4nm were account for 49.1%. Due to these features, the high reversible capacitance of 415F g-1 and the good performance in heavy load discharge were obtained. In addition, the amazing cyclability was observed after 10,000 circles without capacitance fading.

  2. Local charge transport properties of hydrazine reduced monolayer graphene oxide sheets prepared under pressure condition

    DEFF Research Database (Denmark)

    Ryuzaki, Sou; Meyer, Jakob Abild Stengaard; Petersen, Søren Vermehren

    2014-01-01

    Charge transport properties of chemically reduced graphene oxide (RGO) sheets prepared by treatment with hydrazine were examined using conductive atomic force microscopy. The current-voltage (I-V) characteristics of monolayer RGO sheets prepared under atmospheric pressure followed an exponentially...... increase due to 2D variable-range hopping conduction through small graphene domains in an RGO sheet containing defect regions of residual sp3carbon clusters bonded to oxygen groups, whereas RGO sheets prepared in a closed container under moderate pressure showed linear I-V characteristics...... with a conductivity of 267.2-537.5S/m. It was found that the chemical reduction under pressure results in larger graphene domains (sp2networks) in the RGO sheets when compared to that prepared under atmospheric pressure, indicating that the present reduction of GO sheets under the pressure is one of the effective...

  3. Template-free Synthesis of One-dimensional Cobalt Nanostructures by Hydrazine Reduction Route

    Directory of Open Access Journals (Sweden)

    Lan Tianmin

    2011-01-01

    Full Text Available Abstract One-dimensional cobalt nanostructures with large aspect ratio up to 450 have been prepared via a template-free hydrazine reduction route under external magnetic field assistance. The morphology and properties of cobalt nanostructures were characterized by scanning electron microscopy, X-ray diffractometer, and vibrating sample magnetometer. The roles of the reaction conditions such as temperature, concentration, and pH value on morphology and magnetic properties of fabricated Co nanostructures were investigated. This work presents a simple, low-cost, environment-friendly, and large-scale production approach to fabricate one-dimensional magnetic Co materials. The resulting materials may have potential applications in nanodevice, catalytic agent, and magnetic recording.

  4. Chemosensing ability of hydroxynaphthylidene derivatives of hydrazine towards Cu2+: Experimental and computational studies

    Indian Academy of Sciences (India)

    Jayaraman Dessingiou; Jayshree K Khedkar; Chebrolu P Rao

    2014-07-01

    2-Hydroxynaphthylidene derivatives of hydrazine, namely L1, L2 and L3, were synthesized by going through two-step reactions and the products were characterized. The ion recognition properties of these receptors were studied using fluorescence and absorption spectroscopy. The receptors were found to be sensitive and selective towards Cu2+ in methanol solution among the 13 metal ions studied, namely Mn2+, Fe2+, Co2+, Ni2+, Cu2+, Zn2+, Cd2+, Hg2+, Pb2+, Na+, K+, Ca2+ and Mg2+, by exhibiting switch off fluorescence. The stoichiometry of the complexed species was found to be 2:1. The fluorescence quenching with Cu2+ is in the order of L1 > L2 > L3. These conjugates were also found to act as colorimetric sensors for Cu2+ in solution by exhibiting visual colour change. The 2:1 complex shows a centrosymmetric structure based on DFT computations.

  5. 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...

  6. Colorectal cancers and chlorinated water

    Institute of Scientific and Technical Information of China (English)

    Ahmed Mahmoud El-Tawil

    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 concentrations of calcium, magnesium and iron in the public drinking water and prescribing oestrogen in susceptible individuals. Hypo-methylation of genomic DNA could be used as a biological marker for screening for the potential development of colorectal cancers.

  7. [New drugs for colorectal cancer].

    Science.gov (United States)

    Pestalozzi, B C; Jäger, D; Knuth, A

    2004-09-01

    Drug treatment of colorectal cancer has made impressive progress during the past 10 years. In addition to fluorouracil new anticancer drugs like irinotecan and oxaliplatin have become available. The activity of fluorouracil was optimized by using schedules of prolonged infusion. Capecitabine is an oral pro-drug of fluorouracil. When colorectal metastases are limited to the liver they should be resected if possible. Sometimes they can be reduced in size by primary chemotherapy (downstaging) and resected later. Very new and exciting are reports with the monoclonal antibody bevacizumab in combination with chemotherapy. Bevacizumab blocks angiogenesis. So far it is available only in the USA.

  8. Precursor combustion synthesis of nanocrystalline cobalt substituted nickel zinc ferrites from hydrazinated mixed metal fumarates

    Energy Technology Data Exchange (ETDEWEB)

    Gawas, S.G.; Verenkar, V.M.S., E-mail: vmsv@rediffmail.com

    2015-04-10

    Highlights: • Convenient synthesis of hydrazinated mixed metal fumarates under nitrogen atmosphere. • Six hydrazine molecules in precursor provide high exothermicity for the decomposition. • Autocatalytic decomposition of precursors helps in ferritization at 410 °C. • Single domain-superparamagnetic particles of uniform size in the range of 15–30 nm. - Abstract: In present investigation, a systematic approach towards synthesis of nanocrystalline ferrites, Co{sub x}Ni{sub 0.6−x}Zn{sub 0.4}Fe{sub 2}O{sub 4} (x = 0.1 and 0.4) has been reported by room temperature decomposition of precursors, Co{sub x}Ni{sub 0.6−x}Zn{sub 0.4}Fe{sub 2} (C{sub 4}H{sub 2}O{sub 4}){sub 3}·6N{sub 2}H{sub 4} (x = 0.1 and 0.4). The precursor complexes were characterized by Fourier transform infrared spectroscopy (FTIR), chemical analysis and thermal studies like isothermal mass loss, total mass loss, thermogravimetry (TG), derivative of thermogravimetry (DTG) and differential thermal analysis (DTA). The TG–DTG–DTA patterns of both precursors reveal multistep decomposition with complete ferritization at 410 °C. The thermally decomposed products were characterized by X-ray diffractometry (XRD) for phase purity. The FT-IR spectroscopy studies of the same shows complete removal of all organic moieties from decomposed precursors. The nanophasic nature of synthesized ferrites was confirmed by transmission electron microscopy (TEM) analysis as well as from broadening of XRD peaks. The AC magnetization studies show the existence of single domain and superparamagnetic particles, which supports nanosize particles distribution in the ferrite system under study.

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

    Science.gov (United States)

    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.

  10. Galectin-3 silencing inhibits epirubicin-induced ATP binding cassette transporters and activates the mitochondrial apoptosis pathway via β-catenin/GSK-3β modulation in colorectal carcinoma.

    Directory of Open Access Journals (Sweden)

    Yung-Kuo Lee

    Full Text Available Multidrug resistance (MDR, an unfavorable factor compromising the treatment efficacy of anticancer drugs, involves the upregulation of ATP binding cassette (ABC transporters and induction of galectin-3 signaling. Galectin-3 plays an anti-apoptotic role in many cancer cells and regulates various pathways to activate MDR. Thus, the inhibition of galectin-3 has the potential to enhance the efficacy of the anticancer drug epirubicin. In this study, we examined the effects and mechanisms of silencing galectin-3 via RNA interference (RNAi on the β-catenin/GSK-3β pathway in human colon adenocarcinoma Caco-2 cells. Galectin-3 knockdown increased the intracellular accumulation of epirubicin in Caco-2 cells; suppressed the mRNA expression of galectin-3, β-catenin, cyclin D1, c-myc, P-glycoprotein (P-gp, MDR-associated protein (MRP 1, and MRP2; and downregulated the protein expression of P-gp, cyclin D1, galectin-3, β-catenin, c-Myc, and Bcl-2. Moreover, galectin-3 RNAi treatment significantly increased the mRNA level of GSK-3β, Bax, caspase-3, and caspase-9; remarkably increased the Bax-to-Bcl-2 ratio; and upregulated the GSK-3β and Bax protein expressions. Apoptosis was induced by galectin-3 RNAi and/or epirubicin as demonstrated by chromatin condensation, a higher sub-G1 phase proportion, and increased caspase-3 and caspase-9 activity, indicating an intrinsic/mitochondrial apoptosis pathway. Epirubicin-mediated resistance was effectively inhibited via galectin-3 RNAi treatment. However, these phenomena could be rescued after galectin-3 overexpression. We show for the first time that the silencing of galectin-3 sensitizes MDR cells to epirubicin by inhibiting ABC transporters and activating the mitochondrial pathway of apoptosis through modulation of the β-catenin/GSK-3β pathway in human colon cancer cells.

  11. The beta-catenin/TCF-4 complex imposes a crypt progenitor phenotype on colorectal cancer cells

    NARCIS (Netherlands)

    van de Wetering, M; Sancho, E; Verweij, C; de Lau, W; Oving, [No Value; Hurlstone, A; van der Horn, K; Batlle, E; Coudreuse, D; Haramis, AP; Tion-Pon-Fong, M; Moerer, P; van den Born, M; Soete, G; Pals, S; Eilers, M; Medema, R; Clevers, H

    2002-01-01

    The transactivation of TCF target genes induced by Writ pathway mutations constitutes the primary transforming event in colorectal cancer (CRC). We show that disruption of beta-catenin/TCF-4 activity in CRC cells induces a rapid G1 arrest and blocks a genetic program that is physiologically active i

  12. AQUEOUS N-HETEROCYCLIZATION OF PRIMARY AMINES AND HYDRAZINES WITH DIHALIDES: MICROWAVE-ASSISTED SYNTHESES OF N-AZACYCLOALKANES, ISOINDOLE, PYRAZOLE, PYRAZOLIDINE AND PHTHALAZINE DERIVATIVES

    Science.gov (United States)

    The synthesis of nitrogen-containing heterocycles from alkyl dihalides (ditosylates) and primary amines and hydrazines via a simple and efficient cyclocondensation in alkaline aqueous medium that occurs under microwave irradiation is described. This improved greener synthetic met...

  13. Nanostructured SnO{sub 2} encapsulated guar-gum hybrid nanocomposites for electrocatalytic determination of hydrazine

    Energy Technology Data Exchange (ETDEWEB)

    Malik, Priya [Department of Applied Chemistry & Polymer Technology, Delhi Technological University, Shahbad Daulatpur, Main Bawana Road, Delhi 110042 (India); Srivastava, Manish [Department of Physics & Astrophysics, University of Delhi, Delhi 110007 (India); Verma, Ranjana [Solar Energy Material Laboratory, Department of Energy, Tezpur University, Tezpur, Assam 784 028 (India); Kumar, Manish [Department of Applied Chemistry & Polymer Technology, Delhi Technological University, Shahbad Daulatpur, Main Bawana Road, Delhi 110042 (India); Kumar, D., E-mail: dkumar@dce.ac.in [Department of Applied Chemistry & Polymer Technology, Delhi Technological University, Shahbad Daulatpur, Main Bawana Road, Delhi 110042 (India); Singh, Jay, E-mail: jay_singh143@yahoo.co.in [Department of Applied Chemistry & Polymer Technology, Delhi Technological University, Shahbad Daulatpur, Main Bawana Road, Delhi 110042 (India)

    2016-01-01

    The present article deals with synthesis of sol–gel derived tin dioxide (SnO{sub 2}) nanoparticles encapsulated in to guar gum (GG) biopolymer as the organic–inorganic hybrid materials for the determination of hydrazine. The organic–inorganic hybrid combines the perfunctory strength offered by the inorganic SnO{sub 2} nanoparticles with flexible binding sites provided by the organic biopolymer (GG) solution by the ultrasonication. The phase identification, crystalline size, surface morphology and optical properties of prepared SnO{sub 2} and SnO{sub 2}-GG nanocomposites has been investigated through FT-IR, XRD, SEM, AFM, TEM, UV–Vis, and PL techniques. The colloidal solution of SnO{sub 2} and GG is electrophoretically deposited (EPD) onto the indium tin-oxide (ITO) glass substrate and studied for the electrooxidation of hydrazine. Under the optimized experimental conditions, the linearity between the current response and the hydrazine concentration has been obtained in the range of 2–22 mM, with a low detection limit of 2.76 mM and a high sensitivity of 5.72 μA cm{sup −2}. Based on the linear increase in amperometric current, a sensitive hydrazine electrochemical sensor is constructed. The proposed SnO{sub 2}-GG/ITO electrode shows a good response time (35 s), reproducibility, and long-term stability. The obtained results suggest that SnO{sub 2}-GG nanocomposites electrode provides a favorable sensing platform for the electrochemical studies. In addition, the cyclic voltammetry (CV) studies are used to evaluate the kinetic parameters. - Graphical abstract: Synthesis of sol–gel derived tin dioxide (SnO{sub 2}) nanoparticles grafted in to gaur gum (GG) organic–inorganic hybrid nanocomposite for determination of hydrazine (HZ). Under optimized experimental conditions, SnO{sub 2}-GG/ITO electrode shows, linearity 2–22 mM, and detection limit 2.769 mM with high sensitivity of 5.72 μA cm{sup −2}. The results clearly suggest that SnO{sub 2}-GG

  14. Restudy of the Ground Vibrational State of Hydrazine Using the Generalized IAM-like Treatment for the Amino-Wagging Tunneling Motion.

    Science.gov (United States)

    Pyka, Jan; Ohashi, Nobukimi

    2001-05-01

    The amino-wagging tunneling process in hydrazine was treated using the generalized IAM-like method developed by Hougen and Coudert, and Hamiltonian matrix elements were derived for each symmetry species in the combined group-theoretical and IAM-like treatment. Ground state microwave absorption transition data of hydrazine were least squares analyzed again in this treatment to determine axis switching angles for the amino-wagging tunneling process. Copyright 2001 Academic Press.

  15. 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.

  16. 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.

  17. 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.

  18. [The colorectal carcinoma risk factors].

    Science.gov (United States)

    Sobczak, Andrzej; Wawrzyn-Sobczak, Katarzyna; Sobaniec-Lotowska, Maria

    2005-12-01

    Colorectal carcinoma constitutes the second, as for the rate, death cause due to a malignant disease both in the western countries and in Poland. Despite deep knowledge concerning morphogenesis and spread of colorectal carcinoma as well as vast achievements in surgery, chemo- and radiotherapy, the percentage of 5-year-survivals still reaches 40%. According to most authors there are 4 risk factor categories: epidemiological, intestinal, dietetic, and mixed. It is well-known that colorectal carcinoma, like neoplasms localized in other organs and systems, is a disease, in which genetic mutations of somatic cells are the molecular base/source of the disease. The inner innervation of the colon seems to play an important role in carcinoma pathogenesis and spread. At present, 80% of colorectal carcinomas are diagnosed in the advanced stage, with infiltration exceeding the intestinal wall or spreading to neighboring organs, which gives full clinical symptoms. The prognosis as to survival and disease progression is usually poor. Therefore, the ways of early diagnosis, monitoring, and the knowledge of etiological factors are so important in medical practice.

  19. 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.

  20. COLORECTAL-CARCINOMA - AN UPDATE

    NARCIS (Netherlands)

    SINNIGE, HAM; MULDER, NH

    1991-01-01

    During the last decade important advances have occurred in the fields of understanding genesis, molecular biology, detection of "precancerous data", intervention, and metastatic behaviour of colorectal cancer. An important step forward has been made in adjuvant therapy. Better understanding of 5-flu

  1. Five Myths about Colorectal Cancer

    Science.gov (United States)

    ... and processed meat you eat. If you drink alcohol, limit the amount to 1 drink per day for women, 2 per day for men. Don’t use tobacco in any form. Myth: African Americans are not at risk for colorectal cancer. Truth: African-American men and women are diagnosed ...

  2. [Intraoperative staging of colorectal tumors].

    Science.gov (United States)

    Abdurakhmonov, Iu B; Mel'nikov, O R; Egorenkov, V V; Moiseenko, V M

    2007-01-01

    The effectiveness of intraoperative staging of tumor by sentinel node staining with lymphotropic dyes was evaluated in 60 patients with colorectal tumors (colon carcinoma -39, rectal cancer- 21). High sensitivity (84.6% and 87.5%, respectively) and specificity (100% and 100%, respectively) for regional lymph node assessment were identified for both colonic and rectal cancer.

  3. [Systemic therapy for colorectal cancer].

    Science.gov (United States)

    Pestalozzi, B C; Jäger, D; Knuth, A

    2005-06-01

    Drug treatment of colorectal cancer has made impressive progress during the past 10 years. In addition to the traditional 5-fluorouracil, newer anticancer drugs are available including irinotecan and oxaliplatin. Monoclonal antibodies like bevacizumab and cetuximab have been integrated into modern treatment regimens. Based on randomized clinical trials we can formulate rational treatment strategies as outlined in this article.

  4. Optimisation of colorectal cancer treatment

    NARCIS (Netherlands)

    Broek, Colette Bernadine Maria-Theresia van den

    2014-01-01

    Colorectal cancer is one of the most common cancers worldwide. Although there have been several improvements in screening, staging, and treatment in the past decades, survival differences remain. For example among certain subgroups of patients, such as elderly patients and patients with comorbiditie

  5. 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

  6. Deranged Wnt signaling is frequent in hereditary nonpolyposis colorectal cancer

    DEFF Research Database (Denmark)

    Isinger-Ekstrand, Anna; Therkildsen, Christina; Bernstein, Inge

    2011-01-01

    The Wnt signaling pathway is frequently deranged in colorectal cancer and is a key target for future preventive and therapeutic approaches. Colorectal cancers associated with the hereditary nonpolyposis colorectal cancer (HNPCC) syndrome are characterized by wide-spread microsatellite instability...

  7. Diet, lifestyle, and molecular alterations that drive colorectal carcinogenesis

    NARCIS (Netherlands)

    Diergaarde, B.

    2004-01-01

    Environmental factors have been repeatedly implicated in the etiology of colorectal cancer, and much is known about the molecular events involved in colorectal carcinogenesis. The relationships between environmental risk factors and the molecular alterations that drive colorectal carcinogenesis are

  8. 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

  9. Fas/FasL expression in colorectal cancer. An immunohistochemical study.

    Directory of Open Access Journals (Sweden)

    Katarzyna Guzińska-Ustymowicz

    2010-11-01

    Full Text Available The objective of the current study was to assess the expression of Fas ligand (FasL and Fas receptor (FasR as the proteins of the post-mitochondrial apoptotic pathway in colorectal carcinoma and to investigate correlations between their expression and chosen clinico-pathological parameters. The protein expression was analyzed in 50 colorectal carcinoma patients, using the immunohistochemical method. Reaction for FasR was weak in 75.5% and strong in 24.5% of the study patients, as compared to normal glandular epithelium where FasR expression was strong in 100% of cases. On the other hand, FasL expression was found to be weak in 30% and strong in 70% of colorectal cancer patients, as compared to its lack in 100% of normal colorectal epithelium. Statistical analysis showed strong expression of FasL was found to correlate statistically significantly with vascular invasion (p = 0.005. No correlations of FasL and FasR expression in the main mass of tumor was found between other clinic-pathological parameters. Fas ligand and Fas receptor appeared to be of little usefulness as prognostic factors for different groups of colorectal carcinoma patients. However, these proteins could become good therapeutic targets for colorectal carcinoma since their expression differs distinctly between normal intestinal epithelium and cancer cells, and known is the mechanism by which cancer cells escape death via apoptosis-inducing Fas/FasL pathway disorders.

  10. Microcystin-LR promotes epithelial-mesenchymal transition in colorectal cancer cells through PI3-K/AKT and SMAD2.

    Science.gov (United States)

    Ren, Yan; Yang, Mengli; Chen, Meng; Zhu, Qiangqiang; Zhou, Lihua; Qin, Wei; Wang, Ting

    2017-01-04

    Increasing evidences suggest that microcystins, a kind of toxic metabolites, produced by cyanobacteria in contaminated water may contribute to the aggravation of the human colorectal carcinoma. Our previous study showed that microcystin-LR (MC-LR) exposure caused significant invasion and migration of colorectal cancer cells. However, the roles of MC-LR in regulating epithelial-mesenchymal transition (EMT) in colorectal cancer cells remain unknown. In our study, we observed that MC-LR treatment decreased epithelial marker E-cadherin expression and up-regulated the levels of mesenchymal markers Vimentin and Snail in colorectal cancer cells. Moreover, MC-LR stimulated protein expression of SMAD2 and phospho-SMAD2 by PI3-K/AKT activation. The activated PI3-K/AKT and SMAD2 signaling largely accounted for MC-LR-induced EMT, which could be reversed by SMAD2 RNA interference or PI3-K/AKT chemical inhibitor in colorectal cancer cells. Our results show that MC-LR could induce SMAD2 expression to promote colorectal cancer cells EMT, which not only provides a mechanistic insight on MC-LR promotes EMT in colorectal cancer cells, but also support to the development of therapies aimed at SMAD2 in colorectal cancer induced by MC-LR. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  11. NTRK3 is a potential tumor suppressor gene commonly inactivated by epigenetic mechanisms in colorectal cancer.

    Directory of Open Access Journals (Sweden)

    Yanxin Luo

    Full Text Available NTRK3 is a member of the neurotrophin receptor family and regulates cell survival. It appears to be a dependence receptor, and thus has the potential to act as an oncogene or as a tumor suppressor gene. NTRK3 is a receptor for NT-3 and when bound to NT-3 it induces cell survival, but when NT-3 free, it induces apoptosis. We identified aberrantly methylated NTRK3 in colorectal cancers through a genome-wide screen for hypermethylated genes. This discovery led us to assess whether NTRK3 could be a tumor suppressor gene in the colon. NTRK3 is methylated in 60% of colon adenomas and 67% of colon adenocarcinomas. NTRK3 methylation suppresses NTRK3 expression. Reconstitution of NTRK3 induces apoptosis in colorectal cancers, if NT-3 is absent. Furthermore, the loss of NTRK3 expression associates with neoplastic transformation in vitro and in vivo. We also found that a naturally occurring mutant NTRK3 found in human colorectal cancer inhibits the tumor suppressor activity of NTRK3. In summary, our findings suggest NTRK3 is a conditional tumor suppressor gene that is commonly inactivated in colorectal cancer by both epigenetic and genetic mechanisms whose function in the pathogenesis of colorectal cancer depends on the expression status of its ligand, NT-3.

  12. NTRK3 Is a Potential Tumor Suppressor Gene Commonly Inactivated by Epigenetic Mechanisms in Colorectal Cancer

    Science.gov (United States)

    Luo, Yanxin; Kaz, Andrew M.; Kanngurn, Samornmas; Welsch, Piri; Morris, Shelli M.; Wang, Jianping; Lutterbaugh, James D.; Markowitz, Sanford D.; Grady, William M.

    2013-01-01

    NTRK3 is a member of the neurotrophin receptor family and regulates cell survival. It appears to be a dependence receptor, and thus has the potential to act as an oncogene or as a tumor suppressor gene. NTRK3 is a receptor for NT-3 and when bound to NT-3 it induces cell survival, but when NT-3 free, it induces apoptosis. We identified aberrantly methylated NTRK3 in colorectal cancers through a genome-wide screen for hypermethylated genes. This discovery led us to assess whether NTRK3 could be a tumor suppressor gene in the colon. NTRK3 is methylated in 60% of colon adenomas and 67% of colon adenocarcinomas. NTRK3 methylation suppresses NTRK3 expression. Reconstitution of NTRK3 induces apoptosis in colorectal cancers, if NT-3 is absent. Furthermore, the loss of NTRK3 expression associates with neoplastic transformation in vitro and in vivo. We also found that a naturally occurring mutant NTRK3 found in human colorectal cancer inhibits the tumor suppressor activity of NTRK3. In summary, our findings suggest NTRK3 is a conditional tumor suppressor gene that is commonly inactivated in colorectal cancer by both epigenetic and genetic mechanisms whose function in the pathogenesis of colorectal cancer depends on the expression status of its ligand, NT-3. PMID:23874207

  13. The coffee diterpene kahweol suppresses the cell proliferation by inducing cyclin D1 proteasomal degradation via ERK1/2, JNK and GKS3β-dependent threonine-286 phosphorylation in human colorectal cancer cells.

    Science.gov (United States)

    Park, Gwang Hun; Song, Hun Min; Jeong, Jin Boo

    2016-09-01

    Kahweol as a coffee-specific diterpene has been reported to exert anti-cancer properties. However, the mechanism responsible for the anti-cancer effects of kahweol is not fully understood. The main aim of this investigation was to determine the effect of kahweol on cell proliferation and the possible mechanisms in human colorectal cancer cells. Kahweol inhibited markedly the proliferation of human colorectal cancer cell lines such as HCT116, SW480. Kahweol decreased cyclin D1 protein level in HCT116 and SW480 cells. Contrast to protein levels, cyclin D1 mRNA level and promoter activity did not be changed by kahweol treatment. MG132 treatment attenuated kahweol-mediated cyclin D1 downregulation and the half-life of cyclin D1 was decreased in kahweol-treated cells. Kahweol increased phosphorylation of cyclin D1 at threonine-286 and a point mutation of threonine-286 to alanine attenuated cyclin D1 degradation by kahweol. Inhibition of ERK1/2 by PD98059, JNK by SP600125 or GSK3β by LiCl suppressed cyclin D1 phosphorylation and downregulation by kahweol. Furthermore, the inhibition of nuclear export by LMB attenuated cyclin D1 degradation by kahweol. In conclusion, kahweol-mediated cyclin D1 degradation may contribute to the inhibition of the proliferation in human colorectal cancer cells.

  14. Mouse models for the discovery of colorectal cancer driver genes.

    Science.gov (United States)

    Clark, Christopher R; Starr, Timothy K

    2016-01-14

    Colorectal cancer (CRC) constitutes a major public health problem as the third most commonly diagnosed and third most lethal malignancy worldwide. The prevalence and the physical accessibility to colorectal tumors have made CRC an ideal model for the study of tumor genetics. Early research efforts using patient derived CRC samples led to the discovery of several highly penetrant mutations (e.g., APC, KRAS, MMR genes) in both hereditary and sporadic CRC tumors. This knowledge has enabled researchers to develop genetically engineered and chemically induced tumor models of CRC, both of which have had a substantial impact on our understanding of the molecular basis of CRC. Despite these advances, the morbidity and mortality of CRC remains a cause for concern and highlight the need to uncover novel genetic drivers of CRC. This review focuses on mouse models of CRC with particular emphasis on a newly developed cancer gene discovery tool, the Sleeping Beauty transposon-based mutagenesis model of CRC.

  15. Use of activated enol ethers in the synthesis of pyrazoles: reactions with hydrazine and a study of pyrazole tautomerism

    Directory of Open Access Journals (Sweden)

    Denisa Tarabová

    2014-04-01

    Full Text Available Activated enol ethers derived from esters or the dinitrile of malonic acid, or from pentane-2,4-dione were treated with hydrazine hydrate. The structures of the obtained products – pyrazoles 5 – were studied with a focus on tautomerism and supramolecular structure. A reverse addition of the reagents led to the isolation of two novel products, namely bis-enehydrazines 6 with an unsymmetrical arrangement of the formally equivalent subunits.

  16. Effects of Methanol, Methylamine, Formate, N, N-Dimethylhydroxylamine and Formaldehyde on Determining the Methyl Hydrazine Concentration Using Paradime Thylaminobenzaldehyde

    Institute of Scientific and Technical Information of China (English)

    LI; Chuan-bo; CAO; Zhi; BIAN; Xiao-yan; XIAN; Liang; YAN; Tai-hong; ZHENG; Wei-fang

    2012-01-01

    <正>To make sure the feasibility of determining the concentrations of methyl hydrazine (MMH) in 1BP and 2BP using paradime thylaminobenzaldehyde. Researches were done to measure the effects of methanol, methylamine, formate, N, N-dimethylhydroxylamine (DMHAN) and formaldehyde on the method. Though paradime thylaminobenzaldehyde took place condensation reaction with methanol and methylamine, the resultant’s absorbance was zero in 470 nm. So methanol and methylamine did not affect the method of determing the MMH by paradime thylaminobenzaldehyde.

  17. Three-dimensionally grown thorn-like Cu nanowire arrays by fully electrochemical nanoengineering for highly enhanced hydrazine oxidation

    Science.gov (United States)

    Huang, Jianfei; Zhao, Shunan; Chen, Wei; Zhou, Ying; Yang, Xiaoling; Zhu, Yihua; Li, Chunzhong

    2016-03-01

    This communication reports fully electrochemical nanoengineering toward three-dimensionally grown thorn-like Cu nanowire arrays (CNWAs) as a highly efficient and durable electrocatalyst for hydrazine oxidation. Characterized by substantial negative shifting of the onset potential and an enlarged catalytic current density, the CNWAs afforded greatly enhanced hydrazine oxidation activity, even transcending that of the Pt/C catalyst at a higher reaction rate. The parameters of the electrochemical engineering and metallization methods were found to be essentially influential on the microstructure, and thus the electrocatalytic activity of the CNWAs. The present work typifies a flexible and expandible route toward integrated electrodes of metallic 1D nanostructures which are of interest in advancing the performance of cutting-edge electrochemical applications.This communication reports fully electrochemical nanoengineering toward three-dimensionally grown thorn-like Cu nanowire arrays (CNWAs) as a highly efficient and durable electrocatalyst for hydrazine oxidation. Characterized by substantial negative shifting of the onset potential and an enlarged catalytic current density, the CNWAs afforded greatly enhanced hydrazine oxidation activity, even transcending that of the Pt/C catalyst at a higher reaction rate. The parameters of the electrochemical engineering and metallization methods were found to be essentially influential on the microstructure, and thus the electrocatalytic activity of the CNWAs. The present work typifies a flexible and expandible route toward integrated electrodes of metallic 1D nanostructures which are of interest in advancing the performance of cutting-edge electrochemical applications. Electronic supplementary information (ESI) available: Experimental details, additional figures and table. See DOI: 10.1039/c5nr06512g

  18. N'-[5-(4-Nitro-phen-yl)furan-2-yl-methyl-idene]-N,N-diphenyl-hydrazine.

    Science.gov (United States)

    Mendoza, Angel; Cabrera-Vivas, Blanca M; Meléndrez-Luevano, Ruth; Pacheco-Álvarez, Teresa; Carranza, Vladimir

    2010-07-17

    The title compound, C(23)H(17)N(3)O(3), has an E configuration with respect to the C=N bond. The dihedral angle between the two phenyl rings bonded to the hydrazine group is 86.45 (13)°. The furan ring makes dihedral angles of 3.4 (2) and 7.06 (13)°, respectively, with the methyl-idenehydrazine C=N-N plane and the benzene ring.

  19. Reduction of Sulphur-containing Aromatic Nitro Compounds with Hydrazine Hydrate over Iron(Ⅲ) Oxide-MgO Catalyst

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    Sulphur-containing aromatic amines were prepared efficiently in good to excellent yields by reduction of the corresponding sulphur-containing aromatic nitro compounds with hydrazine hydrate in the presence of iron(Ⅲ) oxide-MgO catalyst. The catalyst exhibited high activity and stability for the reduction of sulphur-containing aromatic nitro compounds. The yields of sulphur-containing aromatic amines were up to 91-99 % at 355 K after reduction for 1-4 h over this catalyst.

  20. DECAY ACCELERATING FACTOR AND COLORECTAL CANCER

    Institute of Scientific and Technical Information of China (English)

    高雪芹; 鲁艳芹; 韩金祥

    2004-01-01

    Objective: To review the significance of decay accelerating factor (DAF) in the eolorectal cancer, we searched the data from PubMed and selected the related articles for review. It was found that DAF were expressed in the adenomas and adenocarcinoma of colorectal tissues. The release of DAF in the stool of the patients was also detectable. It increased more significantly in the stool of patients with colorectal cancer than other gastrointestinal cancer. Its detection by ELISA method may render a good test for the noninvasive diagnosis of colorectal cancer. It can be concluded that DAF is expressed extensively in colorectal cancer. And the detection of DAF released in the stool of colorectal cancer patients may be a good noninvasive method for the diagnosis of colorectal cancer.

  1. 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.

  2. 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.

  3. Watchful waiting versus colorectal resection after polypectomy for malignant colorectal polyps

    DEFF Research Database (Denmark)

    Levic, Katarina; Kjær, Monica; Bulut, Orhan;

    2015-01-01

    INTRODUCTION: Unexpected malignancy in removed colorectal polyps is reported in up to 9% of cases. The introduction of screening for colorectal cancer will inevitably increase the number of removed colorectal polyps and therefore also the incidence of malignant polyps. The treatment strategy is e...

  4. Noble metal-free hydrazine fuel cell catalysts: EPOC effect in competing chemical and electrochemical reaction pathways.

    Science.gov (United States)

    Sanabria-Chinchilla, Jean; Asazawa, Koichiro; Sakamoto, Tomokazu; Yamada, Koji; Tanaka, Hirohisa; Strasser, Peter

    2011-04-13

    We report the discovery of a highly active Ni-Co alloy electrocatalyst for the oxidation of hydrazine (N(2)H(4)) and provide evidence for competing electrochemical (faradaic) and chemical (nonfaradaic) reaction pathways. The electrochemical conversion of hydrazine on catalytic surfaces in fuel cells is of great scientific and technological interest, because it offers multiple redox states, complex reaction pathways, and significantly more favorable energy and power densities compared to hydrogen fuel. Structure-reactivity relations of a Ni(60)Co(40) alloy electrocatalyst are presented with a 6-fold increase in catalytic N(2)H(4) oxidation activity over today's benchmark catalysts. We further study the mechanistic pathways of the catalytic N(2)H(4) conversion as function of the applied electrode potential using differentially pumped electrochemical mass spectrometry (DEMS). At positive overpotentials, N(2)H(4) is electrooxidized into nitrogen consuming hydroxide ions, which is the fuel cell-relevant faradaic reaction pathway. In parallel, N(2)H(4) decomposes chemically into molecular nitrogen and hydrogen over a broad range of electrode potentials. The electroless chemical decomposition rate was controlled by the electrode potential, suggesting a rare example of a liquid-phase electrochemical promotion effect of a chemical catalytic reaction ("EPOC"). The coexisting electrocatalytic (faradaic) and heterogeneous catalytic (electroless, nonfaradaic) reaction pathways have important implications for the efficiency of hydrazine fuel cells. © 2011 American Chemical Society

  5. Comparative studies on single-layer reduced graphene oxide films obtained by electrochemical reduction and hydrazine vapor reduction

    Science.gov (United States)

    Wang, Zhijuan; Wu, Shixin; Zhang, Juan; Chen, Peng; Yang, Guocheng; Zhou, Xiaozhu; Zhang, Qichun; Yan, Qingyu; Zhang, Hua

    2012-02-01

    The comparison between two kinds of single-layer reduced graphene oxide (rGO) sheets, obtained by reduction of graphene oxide (GO) with the electrochemical method and hydrazine vapor reduction, referred to as E-rGO and C-rGO, respectively, is systematically studied. Although there is no morphology difference between the E-rGO and C-rGO films adsorbed on solid substrates observed by AFM, the reduction process to obtain the E-rGO and C-rGO films is quite different. In the hydrazine vapor reduction, the nitrogen element is incorporated into the obtained C-rGO film, while no additional element is introduced to the E-rGO film during the electrochemical reduction. Moreover, Raman spectra show that the electrochemical method is more effective than the hydrazine vapor reduction method to reduce the GO films. In addition, E-rGO shows better electrocatalysis towards dopamine than does C-rGO. This study is helpful for researchers to understand these two different reduction methods and choose a suitable one to reduce GO based on their experimental requirements.

  6. Enzyme-free electrochemical immunosensor based on methylene blue and the electro-oxidation of hydrazine on Pt nanoparticles.

    Science.gov (United States)

    Dutta, Gorachand; Nagarajan, Sureshbabu; Lapidus, Lisa J; Lillehoj, Peter B

    2017-06-15

    Enzyme-free electrochemical sensors enable rapid, high sensitivity measurements without the limitations associated with enzyme reporters. However, the performance of non-enzymatic electrochemical sensors tends to suffer from slow electrode kinetics and poor signal stability. We report a new enzyme-free electrochemical immunosensor based on a unique competitive detection scheme using methylene blue (MB), hydrazine and platinum nanoparticles (Pt NPs). This scheme is coupled with a robust immunosandwich format employing a MB-labelled detection antibody as a non-enzymatic reporter. In the presence of the target antigen, surface-immobilized MB consumes interfacial hydrazine thereby diminishing the electro-oxidation of hydrazine on Pt NPs. Thus, the concentration of the antigen is directly proportional to the reduction in the electrochemical signal. For proof-of-concept, this sensor was used to detect Plasmodium falciparum histidine-rich protein 2 (PfHRP2), an important malaria biomarker, in unadulterated human saliva samples. Chronocoulometric measurements showed that this platform exhibits pM-range sensitivity, high specificity and good reproducibility, making it well suited for many biosensing applications including noninvasive diagnostic testing.

  7. Silver nanoparticles sensitized C60(Ag@C60) as efficient electrocatalysts for hydrazine oxidation: Implication for hydrogen generation reaction

    Science.gov (United States)

    Narwade, Shankar S.; Mulik, Balaji B.; Mali, Shivsharan M.; Sathe, Bhaskar R.

    2017-02-01

    Herein, we report the synthesis of silver nanoparticles (Ag NPs; 10 ± 0.5 nm) sensitized Fullerene (C60; 15 ±2 nm) nanocatalysts (Ag@C60) for the first time showing efficient electroatalytic activity for the oxidation of hydrazine demonstrating activity comparable to that of Pt in acidic, neutral and basic media. The performance is comparable with the best available electrocatalytic system and plays a vital role in the overall hydrogen generation reactions from hydrazine as a one of the fuel cell reaction. The materials are synthesized by a simple and scalable synthetic route involving acid functionalization of C60 followed by chemical reduction of Ag+ ions in ethylene glycol at high temperature. The distributation of Silver nanoparticles (Ag NPs) (morphological information) on C60, bonding, its crystal structure, along with activity towards hydrazine oxidation (electrocatalytic) is studied using TEM, XRD, UV-vis, XPS, FTIR and electrochemical (cyclic voltammetry) studies, respectively. The observed efficient electrocatalytic activity of the as-synthesized electrode is attributed to the co-operative response and associated structural defects due to their oxidative functionalization along with thier cooperative functioning at nanodimensions.

  8. Derivatization Ion Chromatography for the Determination of Monoethanolamine in Presence of Hydrazine in PHWR Steam-Water Circuits

    Directory of Open Access Journals (Sweden)

    Ayushi D.

    2011-01-01

    Full Text Available A simple, rapid and accurate method for the determination of monoethanolamine (MEA in PHWR steam-water circuits has been developed. MEA is added in the feed water to provide protection against corrosion while hydrazine is added to scavenge dissolved oxygen. The quantitative determination of MEA in presence of hydrazine was accomplished using derivatization ion chromatography with conductometric detection in nonsuppressed mode. A Metrosep cation 1-2 analytical column and a Metrosep cartridge were used for cation separation. A mixture of 4 mM tartaric acid, 20% acetone and 0.05 mM HNO3 was used as eluent. Acetone in the mobile phase leads to the formation of different derivatives with MEA and hydrazine. The interferences due Na+ and NH4 + were eliminated by adopting a simple pretreatment procedure employing OnGuard-H cartridge. The limit of detection limit of MEA was 0.1 μg mL−1 and the relative standard deviation was 2% for the overall method. The recovery of MEA added was in the range 95%–102%. The method was applied to the determination of MEA in steam generator water samples.

  9. Robotic Colorectal Surgery: A Systematic Review

    OpenAIRE

    Sami AlAsari; Byung Soh Min

    2012-01-01

    Aim. Robotic colorectal surgery may be a way to overcome the limitations of laparoscopic surgery. It is an emerging field; so, we aim in this paper to provide a comprehensive and data analysis of the available literature on the use of robotic technology in colorectal surgery. Method. A comprehensive systematic search of electronic databases was completed for the period from 2000 to 2011. Studies reporting outcomes of robotic colorectal surgery were identified and analyzed. Results. 41 studies...

  10. Identification of a biomarker panel for colorectal cancer diagnosis

    Directory of Open Access Journals (Sweden)

    García-Bilbao Amaia

    2012-01-01

    Full Text Available Abstract Background Malignancies arising in the large bowel cause the second largest number of deaths from cancer in the Western World. Despite progresses made during the last decades, colorectal cancer remains one of the most frequent and deadly neoplasias in the western countries. Methods A genomic study of human colorectal cancer has been carried out on a total of 31 tumoral samples, corresponding to different stages of the disease, and 33 non-tumoral samples. The study was carried out by hybridisation of the tumour samples against a reference pool of non-tumoral samples using Agilent Human 1A 60-mer oligo microarrays. The results obtained were validated by qRT-PCR. In the subsequent bioinformatics analysis, gene networks by means of Bayesian classifiers, variable selection and bootstrap resampling were built. The consensus among all the induced models produced a hierarchy of dependences and, thus, of variables. Results After an exhaustive process of pre-processing to ensure data quality--lost values imputation, probes quality, data smoothing and intraclass variability filtering--the final dataset comprised a total of 8, 104 probes. Next, a supervised classification approach and data analysis was carried out to obtain the most relevant genes. Two of them are directly involved in cancer progression and in particular in colorectal cancer. Finally, a supervised classifier was induced to classify new unseen samples. Conclusions We have developed a tentative model for the diagnosis of colorectal cancer based on a biomarker panel. Our results indicate that the gene profile described herein can discriminate between non-cancerous and cancerous samples with 94.45% accuracy using different supervised classifiers (AUC values in the range of 0.997 and 0.955.

  11. Extended resection for locally advanced colorectal cancer

    Institute of Scientific and Technical Information of China (English)

    WANG Jian-ping; SONG Xin-ming

    2006-01-01

    @@ Colorectal cancer is a common cause of cancer-related mortality.1 In China, it is one of eight cancers in the cancer control blueprint, which are suggested to have comprehensive treatment.Some patients with colorectal cancer presented no symptoms when they were diagnosed, yet the tumor had already penetrated the intestinal wall and involved adjacent organs. If the tumor is localized at time of diagnosis without distant metastases, it is termed locally advanced colorectal cancer (LACC)regardless of whether there is lymph node metastasis. LACC commonly encountered in clinical practice accounts for 5%-10% of all colorectal cancers.2

  12. Alcohol intake, smoking, and colorectal adenoma.

    Science.gov (United States)

    Park, Yeong Mi; Cho, Chang Ho; Kim, Sung Hi; Lee, Jung Eun

    2014-06-01

    Colorectal cancer is the third most common cancer in Korea. Because colorectal adenoma is a precursor lesion of colorectal cancer, primary prevention of colorectal adenomas may be important for reducing morbidity and mortality from the disease. The aim of this study is to examine the association of alcohol consumption and cigarette smoking in relation with colorectal adenoma in a cross-sectional study of Korean adults. A total of 366 participants who underwent colonoscopy were included (113 cases and 255 controls) in this study. Information on alcohol intake and cigarette smoking was collected from structured questionnaires. The odds ratio (ORs) and 95% confidence intervals (CIs) were calculated using the multivariate logistic regression models. Alcohol intake was associated with a higher prevalence of colorectal adenoma in men; compared to non-drinkers, ORs (95% CIs) were 11.49 (2.55-51.89) for 10-20 g/day of alcohol intake and 14.15 (3.31-60.59) for â 20 g/day of alcohol intake (P for trend = 0.003). There was a weaker association of alcohol intake for women than men; however, there was a suggestive increase in the prevalence of colorectal cancer in women. Cigarette smoking was not associated with colorectal adenoma, but we cannot rule out the possibility that this was due to low statistical power. Our study provides evidence to suggest that alcohol intake may contribute to colorectal adenoma in the Korean population. Our study results demonstrate that a larger epidemiologic study is needed.

  13. VMP1 related autophagy and apoptosis in colorectal cancer cells: VMP1 regulates cell death

    Energy Technology Data Exchange (ETDEWEB)

    Qian, Qinyi [Department of Ultrasonograph, Changshu No. 2 People’s Hospital, Changshu (China); Zhou, Hao; Chen, Yan [Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou (China); Shen, Chenglong [Department of General Surgery, Changshu No. 2 People’s Hospital, Changshu (China); He, Songbing; Zhao, Hua; Wang, Liang [Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou (China); Wan, Daiwei, E-mail: 372710369@qq.com [Department of Hepatobiliary Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou (China); Gu, Wen, E-mail: 505339704@qq.com [Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou (China)

    2014-01-17

    Highlights: •This research confirmed VMP1 as a regulator of autophagy in colorectal cancer cell lines. •We proved the pro-survival role of VMP1-mediated autophagy in colorectal cancer cell lines. •We found the interaction between VMP1 and BECLIN1 also existing in colorectal cancer cell lines. -- Abstract: Vacuole membrane protein 1 (VMP1) is an autophagy-related protein and identified as a key regulator of autophagy in recent years. In pancreatic cell lines, VMP1-dependent autophagy has been linked to positive regulation of apoptosis. However, there are no published reports on the role of VMP1 in autophagy and apoptosis in colorectal cancers. Therefore, to address this gap of knowledge, we decided to interrogate regulation of autophagy and apoptosis by VMP1. We have studied the induction of autophagy by starvation and rapamycin treatment in colorectal cell lines using electron microscopy, immunofluorescence, and immunoblotting. We found that starvation-induced autophagy correlated with an increase in VMP1 expression, that VMP1 interacted with BECLIN1, and that siRNA mediated down-regulation of VMP1-reduced autophagy. Next, we examined the relationship between VMP1-dependent autophagy and apoptosis and found that VMP1 down-regulation sensitizes cells to apoptosis and that agents that induce apoptosis down-regulate VMP1. In conclusion, similar to its reported role in other cell types, VMP1 is an important regulator of autophagy in colorectal cell lines. However, in contrast to its role in pancreatic cell lines, in colorectal cancer cells, VMP1-dependent autophagy appears to be pro-survival rather than pro-cell death.

  14. MicroRNA-203-mediated posttranscriptional deregulation of CPEB4 contributes to colorectal cancer progression

    Energy Technology Data Exchange (ETDEWEB)

    Zhong, Xiaohua; Xiao, Yipin; Chen, Chao, E-mail: chenchaopw@126.com; Wei, Xiuwen; Hu, Chen; Ling, Xukun; Liu, Xinbin

    2015-10-16

    Elevated cytoplasmic polyadenylation element-binding 4 (CPEB4) is aberrantly expressed in several malignant cancers. However, its expression pattern, clinical significance, and biological function in colorectal cancer are still unknown. In this study, we demonstrated that CPEB4 is abundantly overexpressed in colorectal cancers and has the potential to be used for predicting clinical outcomes of colorectal cancer patients. We suppressed CPEB4 expression by small interfering RNA (siRNA) in SW480 and LOVO cells to clarify the role of CPEB4 on the cell apoptosis and proliferation in vitro. Further study revealed that knockdown of CPEB4 decreased the expression of anti-apoptotic protein B-cell lymphoma-extra large (Bcl-XL), but enhanced the expression of B-cell lymphoma-2-associated X (Bax). In addition, we indicated that CPEB4 is a novel target of miR-203, a tumor suppressive microRNA. Notably, restoration of CPEB4 in SW480 cells inhibited miR-203-induced apoptosis signaling pathway, which in turn enhanced cell proliferation and suppressed cell apoptosis. Taken together, our findings imply that posttranscriptional deregulation of CPEB4 contributes to the inhibited cell proliferation and the enhanced cell apoptosis in colorectal cancer, and directly targeting CPEB4 by miR-203 might be a novel strategy in colorectal cancer treatment. - Highlights: • CPEB4 is aberrantly expressed in human colorectal cancers. • Knockdown of CPEB4 inhibited colorectal cancer cell proliferation and enhanced apoptosis. • CPEB4 is a direct target of miR-203 and inversely correlates with miR-203 expression. • miR-203 inhibited cell growth and enhanced cell apoptosis in CPEB4 dependent manner. • miR-203 is an upstream regulator of the CPEB4-induced apoptosis pathway.

  15. Thermal chemistry of hydrazine on clean and oxygen- and water-predosed Cu(110) single-crystal surfaces

    Science.gov (United States)

    Yao, Yunxi; Zaera, Francisco

    2016-08-01

    The chemistry of hydrazine on Cu(110) single-crystal surfaces was probed under ultrahigh vacuum (UHV) conditions by temperature-programmed desorption (TPD) and X-ray photoelectron spectroscopy (XPS). Survey TPD experiments identified molecular nitrogen and ammonia as the main desorbing products from thermal activation of the adsorbate, but small amounts of diazene and NH2· radicals were also detected. At saturation coverage, N2 production leads NH3 desorption by approximately 10 K (with TPD peaks at 350 K versus 360 K, respectively), indicating a preference for dehydrogenation over N-N bond scission steps, and additional nitrogen was seen at even lower temperatures (320 K) in experiments starting with even higher doses of hydrazine. On the other hand, the formation of NH3 and NH2·, which desorb in a wide range of temperatures between approximately 300 K and 700 K, dominates in experiments with low N2H4 doses, presumably because a stronger interaction of the N-N bond with the metal in the flat adsorption geometry expected at such low coverages. Dosing at room temperature seems to also facilitate the dissociative adsorption, albeit via dehydrogenation steps that lead to the subsequent production of more significant amounts of diazene and of molecular hydrogen (in addition to N2, NH3, and NH2·). Preadsorption of oxygen on the Cu(110) surface helps stabilize the hydrazine, increasing its desorption temperature and helping with the low-temperature (320 K) production of N2. Coadsorption of hydrazine with water leads to facile proton exchange, as indicated by the production of NH2D in TPD experiments with N2H4 + D2O. This isotope scrambling must occur at cryogenic temperatures because all water desorbs from the surface below 200 K and no other changes in surface chemistry are observed after that. The implications of all this chemistry to practical applications that may use hydrazine in surface reactions with copper, including its use as a reducing agent in atomic layer

  16. Survivorship Care Plan in Promoting Physical Activity in Breast or Colorectal Cancer Survivors in Wisconsin

    Science.gov (United States)

    2017-05-01

    Cancer Survivor; Healthy Subject; Stage I Colorectal Cancer; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage IIA Breast Cancer; Stage IIA Colorectal Cancer; Stage IIB Breast Cancer; Stage IIB Colorectal Cancer; Stage IIC Colorectal Cancer; Stage IIIA Breast Cancer; Stage IIIA Colorectal Cancer; Stage IIIB Breast Cancer; Stage IIIB Colorectal Cancer; Stage IIIC Breast Cancer; Stage IIIC Colorectal Cancer

  17. Adjuvant therapies for colorectal cancer

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    The management of colon and rectal cancer has changed dramatically over the last 25 years. The use of adjuvant therapies has become standard practice in locally advanced (stage Ⅲ and selected stage Ⅱ) colorectal cancer. Improved surgical techniques, chemotherapeutics and radiotherapy are resulting in higher cure rates and the development of agents targeting proliferative and angiogenic pathways offer further promise. Here we explore risk factors for local and distant recurrence after resection of colon and rectal cancer, and the role of adjuvant treatments. Discussion will focus on the evidence base for adjuvant therapies utilised in colorectal cancer, and the treatment of sub-groups such as the elderly and stage Ⅱ disease. The role of adjuvant radiotherapy in rectal cancer in reduction of recurrence will be explored and the role and optimal methods for surveillance post-curative resection with or without adjuvant therapy will also be addressed.

  18. Effects of hydrazine derivatives on vascular smooth muscle contractility, blood pressure and cGMP production in rats: comparison with hydralazine.

    Science.gov (United States)

    Vidrio, Horacio; Fernández, Gabriela; Medina, Martha; Alvarez, Ezequiel; Orallo, Francisco

    2003-01-01

    Hydralazine is a hydrazine derivative used clinically as a vasodilator and antihypertensive agent. Despite numerous studies with the drug, its mechanism of action has remained unknown; guanylate cyclase activation and release of endothelial relaxing factors are thought to be involved in its vasodilator effect. Other hydrazine derivatives are known to stimulate guanylate cyclase and could therefore share the vasodilator activity of hydralazine, although such possibility has not been assessed systematically. In the present study, hydralazine, hydrazine, phenylhydrazine, and isoniazid were evaluated for vascular smooth muscle relaxation in rat aortic rings with and without endothelium, as well as after incubation with the guanylate cyclase inhibitor methylene blue. They were also tested for enhancement of cyclic guanosine monophosphate (cGMP) production by cultured rat aortic smooth muscle cells and for hypotension in the anesthetized rat. All hydrazines relaxed aortic rings, an action unaffected by endothelium removal and, in all cases except hydralazine, antagonized by methylene blue. Only phenylhydrazine increased cGMP production and only hydralazine markedly lowered blood pressure. It was concluded that hydralazine vascular relaxation is independent of endothelium and is not related to guanylate cyclase activation. The other hydrazines studied also elicit endothelium-independent relaxation, but the effect is related to guanylate cyclase. The marked hypotensive effect of hydralazine contrasts with its modest relaxant activity and is not shared by the other hydrazines. The fact that hydrazine and isoniazid produce methylene blue-sensitive relaxation, yet do not enhance cGMP production suggests the need for activating factors present in aortic rings but not in isolated cells.

  19. 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...

  20. Syncytin immunoreactivity in colorectal cancer

    DEFF Research Database (Denmark)

    Larsen, Julie Mou; Christensen, Ib Jarle; Nielsen, Hans Jørgen

    2009-01-01

    monoclonal syncytin antibody we have assessed syncytin expression in a retrospective series of 140 colorectal cancer patients. Variable degrees of syncytin expression were detected in both colonic and rectal tumors and the prognostic impact of such expression was analysed with the Kaplan-Meier method...... and the Cox proportional hazard model. Interestingly, increased syncytin expression was associated with decreased overall survival in rectal but not in colonic cancer patients. Thus, the prognostic impact of syncytin expression appears to vary with the tumor type....

  1. St. John's Wort Attenuates Colorectal Carcinogenesis in Mice through Suppression of Inflammatory Signaling.

    Science.gov (United States)

    Manna, Soumen K; Golla, Srujana; Golla, Jaya Prakash; Tanaka, Naoki; Cai, Yan; Takahashi, Shogo; Krausz, Kristopher W; Matsubara, Tsutomu; Korboukh, Ilia; Gonzalez, Frank J

    2015-09-01

    Despite widespread use as well as epidemiologic indications, there have been no investigations into the effect of St. John's wort (SJW) extract on colorectal carcinogenesis in vivo. This study reports a systematic evaluation of the impact of dietary supplementation of SJW extract on azoxymethane-induced colorectal carcinogenesis in mice. Mice were fed with either AIN-93G (control) diet or SJW extract-supplemented diet (SJW diet) prior to azoxymethane treatment. SJW diet was found to significantly improve the overall survival of azoxymethane-treated mice. Pretreatment with the SJW diet significantly reduced body weight loss as well as decrease of serum albumin and cholesterol levels associated with azoxymethane-induced colorectal tumorigenesis. SJW diet-fed mice showed a significant decrease in tumor multiplicity along with a decrease in incidence of large tumors and a trend toward decreased total tumor volume in a dose-dependent manner. A short-term study, which examined the effect of SJW prior to rectal bleeding, also showed decrease in colorectal polyps in SJW diet-fed mice. Nuclear factor kappa B (NF-κB) and extracellular signal-regulated kinase (ERK1/2) pathways were attenuated by SJW administration. SJW extract resulted in early and continuous attenuation of these pathways in the colon epithelium of SJW diet-fed mice under both short-term and long-term treatment regimens. In conclusion, this study demonstrated the chemopreventive potential of SJW extract against colorectal cancer through attenuation of proinflammatory processes.

  2. Prototype development and test results of a continuous ambient air monitoring system for hydrazine at the 10 ppb level

    Science.gov (United States)

    Meneghelli, Barry; Parrish, Clyde; Barile, Ron; Lueck, Dale E.

    1995-01-01

    A Hydrazine Vapor Area Monitor (HVAM) system is currently being field tested as a detector for the presence of hydrazine in ambient air. The MDA/Polymetron Hydrazine Analyzer has been incorporated within the HVAM system as the core detector. This analyzer is a three-electrode liquid analyzer typically used in boiler feed water applications. The HVAM system incorporates a dual-phase sample collection/transport method which simultaneously pulls ambient air samples containing hydrazine and a very dilute sulfuric acid solution (0.0001 M) down a length of 1/4 inch outside diameter (OD) tubing from a remote site to the analyzer. The hydrazine-laden dilute acid stream is separated from the air and the pH is adjusted by addition of a dilute caustic solution to a pH greater than 10.2 prior to analysis. Both the dilute acid and caustic used by the HVAM are continuously generated during system operation on an "as needed" basis by mixing a metered amount of concentrated acid/base with dilution water. All of the waste water generated by the analyzer is purified for reuse by Barnstead ion-exchange cartridges so that the entire system minimizes the generation of waste materials. The pumping of all liquid streams and mixing of the caustic solution and dilution water with the incoming sample are done by a single pump motor fitted with the appropriate mix of peristaltic pump heads. The signal to noise (S/N) ratio of the analyzer has been enhanced by adding a stirrer in the MDA liquid cell to provide mixing normally generated by the high liquid flow rate designed by the manufacturer. An onboard microprocessor continuously monitors liquid levels, sample vacuum, and liquid leak sensors, as well as handles communications and other system functions (such as shut down should system malfunctions or errors occur). The overall system response of the HVAM can be automatically checked at regular intervals by measuring the analyzer response to a metered amount of calibration standard injected

  3. 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.

  4. Gene expression in colorectal cancer

    DEFF Research Database (Denmark)

    Birkenkamp-Demtroder, Karin; Christensen, Lise Lotte; Olesen, Sanne Harder

    2002-01-01

    Understanding molecular alterations in colorectal cancer (CRC) is needed to define new biomarkers and treatment targets. We used oligonucleotide microarrays to monitor gene expression of about 6,800 known genes and 35,000 expressed sequence tags (ESTs) on five pools (four to six samples in each p...... with a high frequency of loss of heterozygosity. The genes and ESTs presented in this study encode new potential tumor markers as well as potential novel therapeutic targets for prevention or therapy of CRC.......Understanding molecular alterations in colorectal cancer (CRC) is needed to define new biomarkers and treatment targets. We used oligonucleotide microarrays to monitor gene expression of about 6,800 known genes and 35,000 expressed sequence tags (ESTs) on five pools (four to six samples in each...... pool) of total RNA from left-sided sporadic colorectal carcinomas. We compared normal tissue to carcinoma tissue from Dukes' stages A-D (noninvasive to distant metastasis) and identified 908 known genes and 4,155 ESTs that changed remarkably from normal to tumor tissue. Based on intensive filtering 226...

  5. 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.

  6. Conformational effects on hydrazine and OH coadsorption on Ni(111): A first-principles investigation

    Science.gov (United States)

    Agusta, Mohammad Kemal; Purwoko, Prasetiyo Hadi; Saputro, Adhitya Gandaryus; Fathurrahman, Fadjar; Dipojono, Hermawan K.; Diño, Wilson Agerico

    2017-10-01

    Using first-principles Density Functional Theory calculations, we investigated coadsorption of hydrazine (N2H4) and OH on Ni(111) surface. Two types of N2H4 conformations: anti and cis-conformer, with coadsorbed OH on several high symmetry sites on Ni(111) surface were studied. We found that coadsorption with cis-conformer N2H4 significantly modifies OH site preferences while such modification is less profound for coadsorption with anti-conformer N2H4. On the other way around, the cis-confomer N2H4 coadsorption becomes more stable due to the pressence of OH. We identified the electrostatic attractive dipole interaction between the coadsorbed species as the underlying mechanism for the stabilization. This electrostatic interaction is particularly strong for cis-conformer N2H4 due to its large dipole moment. We also found Nsbnd H bond elongation for cis-conformer N2H4 coadsorption with OH due to the interaction between accumulated charge in OH with the H atom of N2H4. Therefore, it can be inferred that coadsorption with OH promotes the dehydrogenation reaction of N2H4 via stabilization of cis-confomer N2H4.

  7. Hydrogen generation from decomposition of hydrous hydrazine over Ni-Ir/CeO2 catalyst

    Directory of Open Access Journals (Sweden)

    Hongbin Dai

    2017-02-01

    Full Text Available The synthesis of highly active and selective catalysts is the central issue in the development of hydrous hydrazine (N2H4·H2O as a viable hydrogen carrier. Herein, we report the synthesis of bimetallic Ni-Ir nanocatalyts supported on CeO2 using a one-pot coprecipitation method. A combination of XRD, HRTEM and XPS analyses indicate that the Ni-Ir/CeO2 catalyst is composed of tiny Ni-Ir alloy nanoparticles with an average size of around 4 nm and crystalline CeO2 matrix. The Ni-Ir/CeO2 catalyst exhibits high catalytic activity and excellent selectivity towards hydrogen generation from N2H4·H2O at mild temperatures. Furthermore, in contrast to previously reported Ni-Pt catalysts, the Ni-Ir/CeO2 catalyst shows an alleviated requirement on alkali promoter to achieve its optimal catalytic performance.

  8. Investigation of a catalytic gas generator for the Space Shuttle APU. [hydrazine Auxiliary Propulsion Unit

    Science.gov (United States)

    Emmons, D. L.; Huxtable, D. D.; Blevins, D. R.

    1974-01-01

    An investigation was conducted to establish the capability of a monopropellant hydrazine catalytic gas generator to meet the requirements specified for the Space Shuttle APU. Detailed analytical and experimental studies were conducted on potential problem areas including long-term nitriding effects on materials, design variables affecting catalyst life, vehicle vibration effects, and catalyst oxidation/contamination. A full-scale gas generator, designed to operate at a chamber pressure of 750 psia and a flow rate of 0.36 lbm/sec, was fabricated and subjected to three separate life test series. The objective of the first test series was to demonstrate the capability of the gas generator to successfully complete 20 simulated Space Shuttle missions in steady-state operation. The gas generator was then refurbished and subjected to a second series of tests to demonstrate the pulse-mode capability of the gas generator during 20 simulated missions. The third series of tests was conducted with a refurbished reactor to further demonstrate pulse-mode capability with a modified catalyst bed.

  9. Influence of ultrasonic waves in the reduction of nitrate to nitrite by hydrazine-Cu(II).

    Science.gov (United States)

    Silva, Luciana A; Korn, Mauro; de Andrade, Jailson B

    2007-02-01

    Colorimetric methods are still important for determining nitrate and nitrite. A critical step in the use of these methods to determine nitrate in low concentrations is the reaction time required to totally reduce nitrate to nitrite, i.e., 24h in the dark. This work involved a study of the influence of ultrasonic irradiation on the nitrate reduction reaction by hydrazine. Our findings indicated that ultrasonic irradiation, associated with copper(II) ion as a catalyst, increased the redox reaction rate, decreasing the reaction time to about 10min when the power of the ultrasonic irradiation was set in 14.0357W. The strong influence of the ultrasonic irradiation in the reduction reaction rates can be sustained by an excellent linear correlation (R(2)=0.9993) between the kinetic constants and ultrasonic powers. Nitrate conversion also increased from 68% to 98% at the latter conditions. It thus become clear that high intensity ultrasound is very beneficial for this reduction reaction to proceed in good yield and in short reaction time in comparison to its silent reaction.

  10. Effects of hydrazine addition on gas evolution and performance of the direct borohydride fuel cell

    Science.gov (United States)

    Qin, H. Y.; Liu, Z. X.; Yin, W. X.; Zhu, J. K.; Li, Z. P.

    A fuel cell configuration using alkaline NaBH 4-N 2H 4 solutions as the fuel is suggested. Gas evolution behaviors and cell performances of alkaline NaBH 4-N 2H 4 solutions on different catalysts have been studied. It is found that gas evolution behaviors are influenced by the applied anodic catalysts and the concentration of NaBH 4 and N 2H 4. NaBH 4 is mainly electro-oxidized on Pd but N 2H 4 is mainly electro-oxidized on Ni and surface-treated Zr-Ni alloy when using NaBH 4-N 2H 4 solutions as the fuel and a composite of Pd, Ni and surface-treated Zr-Ni alloy as the anodic catalyst. The cyclic voltammetry results show that electrochemical oxidation potential of NaBH 4 is higher than that of N 2H 4. Adding hydrazine into alkaline sodium borohydride solutions can suppress gas evolution and improve the cell performance of the DBFC. The performances of fuel cells using NaBH 4-N 2H 4 solutions are comparable to that of fuel cell using N 2H 4 solution.

  11. Stoichiometry and kinetics of the anaerobic ammonium oxidation (Anammox) with trace hydrazine addition.

    Science.gov (United States)

    Yao, Zongbao; Lu, Peili; Zhang, Daijun; Wan, Xinyu; Li, Yulian; Peng, Shuchan

    2015-12-01

    Purpose of this study is to investigate the stoichiometry and kinetics of anaerobic ammonium oxidation (Anammox) with trace hydrazine addition. The stoichiometry was established based on the electron balance of Anammox process with trace N2H4 addition. The stoichiometric coefficients were determined by the proton consumption and the changes in substrates and products. It was found that trace N2H4 addition can increase the yield of Anammox bacteria (AnAOB) and reduce NO3(-) yield, which enhances the Anammox. Subsequently, kinetic model of Anammox with trace N2H4 addition was developed, and the parameters of the anaerobic degradation model of N2H4 were obtained for the first time. The maximum specific substrate utilization rate, half-saturation constant and inhibition constant of N2H4 were 25.09mgN/g VSS/d, 10.42mgN/L and 1393.88mgN/L, respectively. These kinetic parameters might provide important information for the engineering applications of Anammox with trace N2H4 addition.

  12. Cyclooxygenase-2 inhibitors in colorectal cancer prevention: point.

    Science.gov (United States)

    Arber, Nadir

    2008-08-01

    The limited success of current treatments for most advanced common malignancies highlights the importance of cancer prevention. Clinical trials on cyclooxygenase (COX) inhibitor drugs showed the potential of chemoprevention as a strategy for reducing cancer incidence, although not without associated side effects. The attractiveness of these drugs partly stems from an ability to engage multiple mechanisms of action by their potential to influence multiple components of the carcinogenesis pathway, from initiation to progression. There are two isoforms of the COX enzymes. COX-1 is constitutively expressed in normal tissues and serves as a "housekeeper" of mucosal integrity, whereas COX-2 is an immediate early response gene that is highly inducible by neoplastic and inflammatory stimuli. COX-2 is significantly overexpressed in colorectal neoplasms, making it an attractive therapeutic target. The drug market has been revolutionized by the development of preparations targeted selectively against COX-2, and a proof of concept has been achieved. Chemoprevention of colorectal cancer is already possible with celecoxib, but it is still not the ultimate drug of choice especially because of the cardiovascular risk associated with COX-2 inhibitors. Better patient selection and more effective and safer drugs are needed. Celecoxib is probably best used in a subset of individuals at moderate to high colorectal cancer risk and low risk of cardiovascular disease.

  13. Advances and perspectives of colorectal cancer stem cell vaccine.

    Science.gov (United States)

    Guo, Mei; Dou, Jun

    2015-12-01

    Colorectal cancer is essentially an environmental and genetic disease featured by uncontrolled cell growth and the capability to invade other parts of the body by forming metastases, which inconvertibly cause great damage to tissues and organs. It has become one of the leading causes of cancer-related mortality in the developed countries such as United States, and approximately 1.2 million new cases are yearly diagnosed worldwide, with the death rate of more than 600,000 annually and incidence rates are increasing in most developing countries. Apart from the generally accepted theory that pathogenesis of colorectal cancer consists of genetic mutation of a certain target cell and diversifications in tumor microenvironment, the colorectal cancer stem cells (CCSCs) theory makes a different explanation, stating that among millions of colon cancer cells there is a specific and scanty cellular population which possess the capability of self-renewal, differentiation and strong oncogenicity, and is tightly responsible for drug resistance and tumor metastasis. Based on these characteristics, CCSCs are becoming a novel target cells both in the clinical and the basic studies, especially the study of CCSCs vaccines due to induced efficient immune response against CCSCs. This review provides an overview of CCSCs and preparation technics and targeting factors related to CCSCs vaccines in detail.

  14. The UVB1 Vitamin D analogue inhibits colorectal carcinoma progression.

    Science.gov (United States)

    Ferronato, María Julia; Alonso, Eliana Noelia; Gandini, Norberto Ariel; Fermento, María Eugenia; Villegas, María Emilia; Quevedo, Mario Alfredo; Arévalo, Julián; López Romero, Alejandro; Rivadulla, Marcos Lois; Gómez, Generosa; Fall, Yagamare; Facchinetti, María Marta; Curino, Alejandro Carlos

    2016-10-01

    Vitamin D has been shown to display a wide variety of antitumour effects, but their therapeutic use is limited by its severe side effects. We have designed and synthesized a Gemini vitamin D analogue of calcitriol (UVB1) which has shown to display antineoplastic effects on different cancer cell lines without causing hypercalcemia. The aim of this work has been to investigate, by employing in silico, in vitro, and in vivo assays, whether UVB1 inhibits human colorectal carcinoma progression. We demonstrated that UVB1 induces apoptotic cell death and retards cellular migration and invasion of HCT116 colorectal carcinoma cells. Moreover, the analogue reduced the tumour volume in vivo, and modulated the expression of Bax, E-cadherin and nuclear β-catenin in tumour animal tissues without producing toxic effects. In silico analysis showed that UVB1 exhibits greater affinity for the ligand binding domain of vitamin D receptor than calcitriol, and that several characteristics in the three-dimensional conformation of VDR may influence the biological effects. These results demonstrate that the Gemini vitamin D analogue affects the growth of the colorectal cancer and suggest that UVB1 is a potential chemotherapeutic agent for treatment of this disease.

  15. Danish Colorectal Cancer Group Database

    Directory of Open Access Journals (Sweden)

    Ingeholm P

    2016-10-01

    Full Text Available Peter Ingeholm,1,2 Ismail Gögenur,1,3 Lene H Iversen1,4 1Danish Colorectal Cancer Group Database, Copenhagen, 2Department of Pathology, Herlev University Hospital, Herlev, 3Department of Surgery, Roskilde University Hospital, Roskilde, 4Department of Surgery P, Aarhus University Hospital, Aarhus C, Denmark 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 or treated in a surgical department of a public Danish hospital. Main variables: 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. 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 2001–2003 to <2% since 2013. Conclusion: The database is a national population-based clinical database with high patient and data completeness for the perioperative period

  16. 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....

  17. Economic burden of colorectal cancer in Korea.

    Science.gov (United States)

    Byun, Ju-Young; Yoon, Seok-Jun; Oh, In-Hwan; Kim, Young Ae; Seo, Hye-Young; Lee, Yo-Han

    2014-03-01

    The incidence and survival rate of colorectal cancer in Korea are increasing because of improved screening, treatment technologies, and lifestyle changes. In this aging population, increases in economic cost result. This study was conducted to estimate the economic burden of colorectal cancer utilizing claims data from the Health Insurance Review and Assessment Service. Economic burdens of colorectal cancer were estimated using prevalence data and patients were defined as those who received ambulatory treatment from medical institutions or who had been hospitalized due to colorectal cancer under the International Classification of Disease 10th revision codes from C18-C21. The economic burdens of colorectal cancer were calculated as direct costs and indirect costs. The prevalence rate (per 100 000 people) of those who were treated for colorectal cancer during 2010 was 165.48. The economic burdens of colorectal cancer in 2010 were 3 trillion and 100 billion Korean won (KRW), respectively. Direct costs included 1 trillion and 960 billion KRW (62.85%), respectively and indirect costs were 1 trillion and 160 billion (37.15%), respectively. Colorectal cancer has a large economic burden. Efforts should be made to reduce the economic burden of the disease through primary and secondary prevention.

  18. 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

  19. Diet and colorectal cancer risk and survival

    NARCIS (Netherlands)

    Winkels, R.M.; Duijnhoven, van F.J.B.; Heine-Bröring, R.C.; Kampman, E.

    2013-01-01

    Unhealthy dietary and other lifestyle factors account for 20–45% of all colorectal cancer cases. Being overweight or obese, having a high intake of red and processed meat and alcohol increase the risk of colorectal cancer, while a high intake of dairy products, fruits and vegetables, foods containin

  20. Increased hepcidin expression in colorectal carcinogenesis

    Institute of Scientific and Technical Information of China (English)

    Douglas G Ward; Keith Roberts; Matthew J Brookes; Howard Joy; Ashley Martin; Tariq Ismail; Robert Spychal; Tariq Iqbal; Chris Tselepis

    2008-01-01

    AIM:To investigate whether the iron stores regulator hepcidin is implicated in colon cancer-associated anae-mia and whether it might have a role in colorectal car-cinogenesis.METHODS:Mass spectrometry (MALDI-TOF MS and SELDI-TOF MS) was employed to measure hepcidin in urine collected from 56 patients with colorectal cancer.Quantitative Real Time RT-PCR was utilised to determine hepcidin mRNA expression in colorectal cancer tissue.Hepcidin cellular localisation was determined using im-munohistochemistry.RESULTS:We demonstrate that whilst urinary hepcidin expression was not correlated with anaemia it was posi-tively associated with increasing T-stage of colorectal cancer (P<0.05).Furthermore,we report that hepcidin mRNA is expressed in 34% of colorectal cancer tissue specimens and was correlated with ferroportin repres-sion.This was supported by hepcidin immunoreactivity in colorectal cancer tissue.CONCLUSION:We demonstrate that systemic hepcidin expression is unlikely to be the cause of the systemic anaemia associated with colorectal cancer.However,we demonstrate for the first time that hepcidin is expressed by colorectal cancer tissue and that this may represent a novel oncogenic signalling mechanism.

  1. Best practice in colorectal cancer care.

    Science.gov (United States)

    Taylor, Claire

    Nurses need up-to-date knowledge of colorectal cancer. This article provides an overview of the aetiology and risk factors for this disease, diagnostic and staging investigations, treatment options and future care. Managing colorectal cancer is complex. Patients can have a range of healthcare needs. Nurses play an increasingly important role in informing, supporting and coordinating care to improve patients' quality of life.

  2. Diet and colorectal cancer risk and survival

    NARCIS (Netherlands)

    Winkels, R.M.; Duijnhoven, van F.J.B.; Heine-Bröring, R.C.; Kampman, E.

    2013-01-01

    Unhealthy dietary and other lifestyle factors account for 20–45% of all colorectal cancer cases. Being overweight or obese, having a high intake of red and processed meat and alcohol increase the risk of colorectal cancer, while a high intake of dairy products, fruits and vegetables, foods

  3. Optimizing Outcomes of Colorectal Cancer Screening

    NARCIS (Netherlands)

    R.G.S. Meester (Reinier)

    2017-01-01

    markdownabstractColorectal cancer screening is a leading cause of cancer deaths. Screening for colorectal cancer is implemented in an increasing number of settings, but performance of programs is often suboptimal. In this thesis, advanced modeling, informed by empirical data, was used to identify ar

  4. Optimizing Outcomes of Colorectal Cancer Screening

    NARCIS (Netherlands)

    R.G.S. Meester (Reinier)

    2017-01-01

    markdownabstractColorectal cancer screening is a leading cause of cancer deaths. Screening for colorectal cancer is implemented in an increasing number of settings, but performance of programs is often suboptimal. In this thesis, advanced modeling, informed by empirical data, was used to identify

  5. 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…

  6. Genetic polymorphisms of XRCC1, alcohol consumption, and the risk of colorectal cancer in Japan.

    Science.gov (United States)

    Yin, Guang; Morita, Makiko; Ohnaka, Keizo; Toyomura, Kengo; Hamajima, Nobuyuki; Mizoue, Tetsuya; Ueki, Takashi; Tanaka, Masao; Kakeji, Yoshihiro; Maehara, Yoshihiko; Okamura, Takeshi; Ikejiri, Koji; Futami, Kitaroh; Yasunami, Yohichi; Maekawa, Takefumi; Takenaka, Kenji; Ichimiya, Hitoshi; Terasaka, Reiji

    2012-01-01

    X-ray cross-complementing group 1 (XRCC1) polymorphisms affect DNA repair capacity and may therefore be of importance in colorectal carcinogenesis. Alcohol consumption, an important risk factor for colorectal cancer, may induce carcinogenesis through DNA damage caused by the toxic effects of alcohol or its metabolites. Therefore, we examined the associations of XRCC1 Arg399Gln, Arg280His, and Arg194Trp polymorphisms with colorectal cancer and the impact of the association between alcohol consumption and colorectal cancer risk. This case-control study in Fukuoka, Japan including 685 cases and 778 controls. The cases were incident patients with histologically confirmed colorectal adenocarcinoma. The controls were randomly selected community subjects. The XRCC1 399Gln/Gln genotype was significantly associated with colorectal cancer risk (adjusted odds ratio [OR] 1.57, 95% CI 1.01-2.42; relative to 399Arg/Arg genotype). The association was strongest in individuals with high alcohol consumption. The Arg280His polymorphism modified the association between alcohol consumption and colorectal cancer risk (interaction P = 0.049). The OR of colorectal cancer in individuals with the 280His allele was 0.45 (95% CI 0.26-0.78) as compared with the 280Arg/Arg genotype limited to the 399Gln allele (interaction P = 0.001). The adjusted ORs for 399Gln/Gln-280Arg/Arg-194Arg/Arg and 399Arg/Gln-280Arg/Arg-194Arg/Trp were 1.71 (95% CI 1.02-2.87) and 1.57 (95% CI 1.05-2.33), respectively, with 399Arg/Arg-280Arg/Arg-194Arg/Arg as reference (interaction P = 0.418). The findings are additional evidence that individuals with the XRCC1 399Gln/Gln genotype have an increased risk of colorectal cancer, and that XRCC1 polymorphisms have an important role in colorectal cancer risk associated with alcohol consumption or gene-gene interaction.

  7. The effect of statins in colorectal cancer is mediated through the bone morphogenetic protein pathway

    NARCIS (Netherlands)

    Kodach, Liudmila L.; Bleuming, Sylvia A.; Peppelenbosch, Maikel P.; Hommes, Daniel W.; Van Den Brink, Gus R.; Hardwick, James C. H.

    2007-01-01

    Background & Aims: Epidemiological evidence suggests that statins prevent colorectal cancer (CRC), but the biological mechanism remains obscure. Statins induce bone morphogenetic protein (BMP) expression in bone cells. We have previously shown that BMPs act as tumor suppressors in CRC. We hypothesiz

  8. SNHG5 promotes colorectal cancer cell survival by counteracting STAU1-mediated mRNA destabilization

    DEFF Research Database (Denmark)

    Damas, Nkerorema Djodji; Marcatti, Michela; Côme, Christophe;

    2016-01-01

    We currently have limited knowledge of the involvement of long non-coding RNAs (lncRNAs) in normal cellular processes and pathologies. Here, we identify and characterize SNHG5 as a stable cytoplasmic lncRNA with up-regulated expression in colorectal cancer. Depletion of SNHG5 induces cell cycle...... characterize SNHG5 as a lncRNA promoting tumour cell survival in colorectal cancer and delineate a novel mechanism in which a cytoplasmic lncRNA functions through blocking the action of STAU1....

  9. Estrogen and colorectal cancer incidence and mortality.

    Science.gov (United States)

    Lavasani, Sayeh; Chlebowski, Rowan T; Prentice, Ross L; Kato, Ikuko; Wactawski-Wende, Jean; Johnson, Karen C; Young, Alicia; Rodabough, Rebecca; Hubbell, F Allan; Mahinbakht, Ali; Simon, Michael S

    2015-09-15

    The preponderance of observational studies describe an association between the use of estrogen alone and a lower incidence of colorectal cancer. In contrast, no difference in the incidence of colorectal cancer was seen in the Women's Health Initiative (WHI) randomized, placebo-controlled trial with estrogen alone after a mean intervention of 7.1 years and cumulative follow-up of 13.2 years. This study extends these findings by providing detailed analyses of the effects of estrogen alone on the histology, grade, and stage of colorectal cancer, relevant subgroups, and deaths from and after colorectal cancer. The WHI study was a randomized, double-blind, placebo-controlled trial involving 10,739 postmenopausal women with prior hysterectomy. Participants were assigned to conjugated equine estrogen at 0.625 mg/d (n = 5279) or a matching placebo (n = 5409). Rates of colorectal cancer diagnoses and deaths from and after colorectal cancer were assessed throughout the study. Colorectal cancer rates in the estrogen-alone and placebo groups were comparable: 0.14% and 0.12% per year, respectively (hazard ratio [HR], 1.13; 95% confidence interval [CI], 0.83-1.58; P = .43). Bowel screening examinations were comparable between the 2 groups throughout the study. The grade, stage, and location of colorectal cancer did not differ between the randomization groups. There were more colorectal cancer deaths in the estrogen-alone group (34 [0.05%] vs 24 [0.03%]; HR, 1.46, 95% CI, 0.86-2.46; P = .16), but the difference was not statistically significant. The colorectal cancer incidence was higher for participants with a history of colon polyp removal in the estrogen-alone group (0.23% vs 0.02%; HR, 13.47; nominal 95% CI, 1.76-103.0; P colorectal cancer or deaths from or after colorectal cancer. A possibly higher risk of colorectal cancer in women with prior colon polyp removal who use estrogen alone requires confirmation. © 2015 American Cancer Society.

  10. The level of claudin-7 is reduced as an early event in colorectal carcinogenesis

    Directory of Open Access Journals (Sweden)

    Tveit Kjell M

    2011-02-01

    Full Text Available Abstract Background Compromised epithelial barriers are found in dysplastic tissue of the gastrointestinal tract. Claudins are transmembrane proteins important for tight junctions. Claudins regulate the paracellular transport and are crucial for maintaining a functional epithelial barrier. Down-regulation of the oncogenic serine protease, matriptase, induces leakiness in epithelial barriers both in vivo and in vitro. We found in an in-silico search tight co-regulation between matriptase and claudin-7 expression. We have previously shown that the matriptase expression level decreases during colorectal carcinogenesis. In the present study we investigated whether claudin-7 expression is likewise decreased during colorectal carcinogenesis, thereby causing or contributing to the compromised epithelial leakiness of dysplastic tissue. Methods The mRNA level of claudin-7 (CLDN7 was determined in samples from 18 healthy individuals, 100 individuals with dysplasia and 121 colorectal cancer patients using quantitative real time RT-PCR. In addition, immunohistochemical stainings were performed on colorectal adenomas and carcinomas, to confirm the mRNA findings. Results A 2.7-fold reduction in the claudin-7 mRNA level was found when comparing the biopsies from healthy individuals with the biopsies of carcinomas (p claudin-7 mRNA levels were also detected in mild/moderate dysplasia (p Conclusions Our results show that the claudin-7 mRNA level is decreased already as an early event in colorectal carcinogenesis, probably contributing to the compromised epithelial barrier in adenomas.

  11. Association of Calcium-Sensing Receptor (CASR rs 1801725 with Colorectal Cancer

    Directory of Open Access Journals (Sweden)

    Fateme Rostami

    2012-07-01

    Full Text Available Background: Calcium induces apoptosis in intestinal epithelial cells and subsequently prevents colorectal cancer through ion calcium receptor. Calcium-sensing receptor mutation reduces the expression of this receptor, and subsequently in reduces calcium transportation. Many studies have shown that Calcium-sensing receptor gene polymorphism may increase the risk of colorectal cancer. The purpose of this study is to assess the prevalence of calcium-sensing receptor polymorphisms (rs 1801725 in Iran society and to examine the role of this polymorphism in the increased risk of colorectal cancer (CRC.Materials and Methods: The research was a case-control study. 105 patients with colorectal cancer and 105 controls were randomly studied using polymerase chain reaction and restriction fragment length polymorphism. χ2 test and software 16- SPSS were used for statistical analysis.Results: In patient samples, the frequency of the genotypes TT, GT, GG in gene CASR rs 1801725 was respectively 64.8, 32.4, and 2.9 and the frequency of this polymorphism in control samples was respectively 51.2, 45.7, and 2.9. Frequency of allele G in patient samples was 0/48 and frequency of allele T was 0.25. In addition, Frequency of allele G in control samples was 0.74 and Frequency of allele T was calculated 0.19.Conclusion: The results show that calcium-sensing receptor variant (1801725 rs is not associated with increased risk of colorectal cancer.

  12. Histological and molecular evaluation of patient-derived colorectal cancer explants.

    Directory of Open Access Journals (Sweden)

    Joshua M Uronis

    Full Text Available Mouse models have been developed to investigate colorectal cancer etiology and evaluate new anti-cancer therapies. While genetically engineered and carcinogen-induced mouse models have provided important information with regard to the mechanisms underlying the oncogenic process, tumor xenograft models remain the standard for the evaluation of new chemotherapy and targeted drug treatments for clinical use. However, it remains unclear to what extent explanted colorectal tumor tissues retain inherent pathological features over time. In this study, we have generated a panel of 27 patient-derived colorectal cancer explants (PDCCEs by direct transplantation of human colorectal cancer tissues into NOD-SCID mice. Using this panel, we performed a comparison of histology, gene expression and mutation status between PDCCEs and the original human tissues from which they were derived. Our findings demonstrate that PDCCEs maintain key histological features, basic gene expression patterns and KRAS/BRAF mutation status through multiple passages. Altogether, these findings suggest that PDCCEs maintain similarity to the patient tumor from which they are derived and may have the potential to serve as a reliable preclinical model that can be incorporated into future strategies to optimize individual therapy for patients with colorectal cancer.

  13. The Dutch surgical colorectal audit.

    Science.gov (United States)

    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

    2013-10-01

    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 Institute for Clinical Auditing (DICA). This article illustrates key elements of the DSCA and results of three years of auditing. Key elements include: a leading role of the professional association with integration of the audit in the national quality assurance policy; web-based registration by medical specialists; weekly updated online feedback to participants; annual external data verification with other data sources; improvement projects. In two years, all Dutch hospitals participated in the audit. Case-ascertainment was 92% in 2010 and 95% in 2011. External data verification by comparison with the Netherlands Cancer Registry (NCR) showed high concordance of data items. Within three years, guideline compliance for diagnostics, preoperative multidisciplinary meetings and standardised reporting increased; complication-, re-intervention and postoperative mortality rates decreased significantly. The success of the DSCA is the result of effective surgical collaboration. The leading role of the ASN in conducting the audit resulted in full participation of all colorectal surgeons in the Netherlands. By integrating the audit into the ASNs' quality assurance policy, it could be used to set national quality standards. Future challenges include reduction of administrative burden; expansion to a multidisciplinary registration; and addition of financial information and patient reported outcomes to the audit data. Copyright © 2013 Elsevier Ltd. All rights reserved.

  14. Arctigenin Inhibits Lung Metastasis of Colorectal Cancer by Regulating Cell Viability and Metastatic Phenotypes.

    Science.gov (United States)

    Han, Yo-Han; Kee, Ji-Ye; Kim, Dae-Seung; Mun, Jeong-Geon; Jeong, Mi-Young; Park, Sang-Hyun; Choi, Byung-Min; Park, Sung-Joo; Kim, Hyun-Jung; Um, Jae-Young; Hong, Seung-Heon

    2016-08-27

    Arctigenin (ARC) has been shown to have an anti-cancer effect in various cell types and tissues. However, there have been no studies concerning metastatic colorectal cancer (CRC). In this study, we investigated the anti-metastatic properties of ARC on colorectal metastasis and present a potential candidate drug. ARC induced cell cycle arrest and apoptosis in CT26 cells through the intrinsic apoptotic pathway via MAPKs signaling. In several metastatic phenotypes, ARC controlled epithelial-mesenchymal transition (EMT) through increasing the expression of epithelial marker E-cadherin and decreasing the expressions of mesenchymal markers; N-cadherin, vimentin, β-catenin, and Snail. Moreover, ARC inhibited migration and invasion through reducing of matrix metalloproteinase-2 (MMP-2) and MMP-9 expressions. In an experimental metastasis model, ARC significantly inhibited lung metastasis of CT26 cells. Taken together, our study demonstrates the inhibitory effects of ARC on colorectal metastasis.

  15. Induction of Apoptosis and Cell Cycle Arrest in Human Colorectal Carcinoma by Litchi Seed Extract

    Directory of Open Access Journals (Sweden)

    Chih-Ping Hsu

    2012-01-01

    Full Text Available The Litchi (Litchi chinensis fruit products possess rich amounts of flavanoids and proanthocyanidins. Its pericarp has been shown to inhibit breast and liver cancer cell growth. However, the anticolorectal cancer effect of Litchi seed extract has not yet been reported. In this study, the effects of polyphenol-rich Litchi seed ethanol extract (LCSP on the proliferation, cell cycle, and apoptosis of two colorectal cancer cell lines Colo320DM and SW480 were examined. The results demonstrated that LCSP significantly induced apoptotic cell death in a dose-dependent manner and arrested cell cycle in G2/M in colorectal carcinoma cells. LCSP also suppressed cyclins and elevated the Bax : Bcl-2 ratio and caspase 3 activity. This study provides in vitro evidence that LCSP serves as a potential chemopreventive agent for colorectal cancer.

  16. Portal thrombosis and steatosis after preoperative chemotherapy with FOLFIRI-bevacizumab for colorectal liver metastases

    Institute of Scientific and Technical Information of China (English)

    Matteo Donadon; Jean-Nicolas Vauthey; Evelyne M Loyer; Chusilp Charnsangavej; Eddie K Abdalla

    2006-01-01

    In order to discuss the role of preoperative chemotherapy for colorectal liver metastases, which is used frequently before hepatic resection, even in patients with resectable disease at presentation, we herein report the development of two complications, partial portal vein thrombosis and hepatic steatosis with lobular inflammation, during the course of preoperative chemotherapy with FOLFIRI plus bevacizumab for colorectal liver metastases, which recognition led to timely discontinuation of chemotherapy as well as a change in the surgical strategy to resect the tumors and the damaged liver through advanced techniques.We conclude that duration of treatment and drug doses and combinations may impact the development of chemotherapy-induced liver injury. Surgeons and medical oncologists must work together to devise safe, rational,and oncologically appropriate treatments for patients with multiple colorectal liver metastases, and to improve the understanding of the pathogenesis of chemotherapyinduced liver injury.

  17. Arctigenin Inhibits Lung Metastasis of Colorectal Cancer by Regulating Cell Viability and Metastatic Phenotypes

    Directory of Open Access Journals (Sweden)

    Yo-Han Han

    2016-08-01

    Full Text Available Arctigenin (ARC has been shown to have an anti-cancer effect in various cell types and tissues. However, there have been no studies concerning metastatic colorectal cancer (CRC. In this study, we investigated the anti-metastatic properties of ARC on colorectal metastasis and present a potential candidate drug. ARC induced cell cycle arrest and apoptosis in CT26 cells through the intrinsic apoptotic pathway via MAPKs signaling. In several metastatic phenotypes, ARC controlled epithelial-mesenchymal transition (EMT through increasing the expression of epithelial marker E-cadherin and decreasing the expressions of mesenchymal markers; N-cadherin, vimentin, β-catenin, and Snail. Moreover, ARC inhibited migration and invasion through reducing of matrix metalloproteinase-2 (MMP-2 and MMP-9 expressions. In an experimental metastasis model, ARC significantly inhibited lung metastasis of CT26 cells. Taken together, our study demonstrates the inhibitory effects of ARC on colorectal metastasis.

  18. Theoretical studies on vibrational spectra, thermodynamic properties, detonation properties and pyrolysis mechanism for 1,2-bis(2,4,6-trinitrophenyl) hydrazine.

    Science.gov (United States)

    Xiao-Hong, Li; Rui-Zhou, Zhang; Xian-Zhou, Zhang

    2012-07-01

    The thermal stability and pyrolysis mechanism of 1,2-bis(2,4,6-trinitrophenyl) hydrazine were investigated based on fully optimized molecular geometric structures. The results demonstrate the existence of intramolecular hydrogen bond interactions 1,2-bis(2,4,6-trinitrophenyl) hydrazine. The assigned infrared spectrum was also obtained; the results reveal four main characteristic regions in the calculated IR spectra of the title compound. Detonation velocities (D) and pressures (P) were also evaluated by using Kamlet-Jacobs equations based on the calculated density and heat of formation. Thermal stability and the pyrolysis mechanism of 1,2-bis(2,4,6-trinitrophenyl) hydrazine were investigated by calculating the bond dissociation energies at the B3LYP/6-31 G* level.

  19. Structures of N- (2,3,4,6-Tetra- O-acetyl-β- D-glycosyl) thiocar-bamic Benzoyl Hydrazine

    Institute of Scientific and Technical Information of China (English)

    ZHANG,Shu-Sheng(张书圣); LIN,Jie-Hua(林洁华); JIAN,Fang-Fang(建方方); JIAO,Kui(焦奎)

    2002-01-01

    The crystal structure of N-( 2, 3 , 4 , 6-tetra-O-acetyl- β- D-glycosyl)-thiocarbamic benzoyl hydrazine ( C22 H27 N3O9S) was determined by X-ray diffraction method. The hexopyranosyl ring adopts a chair conformation. All the ring substituents are in the equatorial positions. The acetoxyl-methyl group is in synclinal conformation. The S atom is in synperiplanar conformation while the benzoyl hydrazine moiety is anti-periplanar. The thiocarbamic moiety is almost coplanar with the benzoyl hydrazine group. There are two intramolecular hydrogen bonds and one intermolecular hydrogen bond for each molecule in the crystal structure. The molecules form a network structure through intermolecular hydrogen bonds.

  20. Facile growth of Ag@Pt bimetallic nanorods on electrochemically reduced graphene oxide for an enhanced electrooxidation of hydrazine

    Indian Academy of Sciences (India)

    Jeena S E; Selvaraju T

    2016-03-01

    An efficient transducer was constructed by the direct growth of bimetallic Ag@Pt nanorods (NRDs) on L−tryptophan functionalized electrochemically reduced graphene oxide (L−ERGO) modified electrode using galvanic displacement method for the electrooxidation of hydrazine.Initially, one dimensionalbimetallic Ag@Cu core−shell NRDs were grown on L−ERGO modified electrode by simple seed mediated growth method. Then, the Cu shells at bimetallic NRDs were exchanged by Pt through galvanic displacement method. Accordingly, the synergetic effect produced by the combination of Ag and Pt as NRDs at L−ERGO surface enabled an enhancement in the electrocatalytic efficiency for hydrazine oxidation. L−ERGO supported bimetallic Ag@Pt NRDs were characterised by scanning electron microscopy (SEM), energy dispersive X-ray spectroscopy (EDX) and cyclic voltammetric techniques. Finally, the modified electrode was successfully used for the electrooxidation of hydrazine in PB (pH 7.4)with a detection limit of 6*10−7M(SdivN=3). Importantly, the presence of Pt on Ag surface plays a vital role in the electrooxidation of [N2H4] at−0.2 V with an onset potential at−0.5 V where its overpotential has decreased. On the other hand, L−ERGO nanosheets tend to facilitate an effective immobilization of low density Ag seeds (Agseeds) on its surface. Chronoamperometric studies were used to study the linear correlation of [N2H4] between 1 mM and 10 mM. The modified electrode shows a high sensitivity and selectivity for a trace amount of N2H4 in the presence of different interfering cations and anions