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Sample records for human colonic adenocarcinoma

  1. Effects of adrenaline in human colon adenocarcinoma HT-29 cells.

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    Wong, Helen P S; Ho, Judy W C; Koo, Marcel W L; Yu, Le; Wu, William K K; Lam, Emily K Y; Tai, Emily K K; Ko, Joshua K S; Shin, Vivian Y; Chu, Kent Man; Cho, Chi Hin

    2011-06-20

    Stress has been implicated in the development of cancers. Adrenaline levels are increased in response to stress. The effects of adrenaline on colon cancer are largely unknown. The aims of the study are to determine the effects of adrenaline in human colon adenocarcinoma HT-29 cells and the possible underlying mechanisms involved. The effect of adrenaline on HT-29 cell proliferation was determined by [(3)H] thymidine incorporation assay. Expression of cyclooxygenase-2 (COX-2) and vascular endothelial growth factor (VEGF) were detected by Western blot. Matrix metalloproteinase-9 (MMP-9) activity and prostaglandin E(2) (PGE(2)) release were determined by zymography and enzyme immunoassay, respectively. Adrenaline stimulated HT-29 cell proliferation. This was accompanied by the enhanced expression of COX-2 and VEGF in HT-29 cells. Adrenaline also upregulated MMP-9 activity and PGE(2) release. Adrenaline stimulated HT-29 cell proliferation which was reversed by COX-2 inhibitor sc-236. COX-2 inhibitor also reverted the action of adrenaline on VEGF expression and MMP-9 activity. Further study was performed to determine the involvement of β-adrenoceptors. The stimulatory action of adrenaline on colon cancer growth was blocked by atenolol and ICI 118,551, a β(1)- and β(2)-selective antagonist, respectively. This signified the role of β-adrenoceptors in this process. In addition, both antagonists also abrogated the stimulating actions of adrenaline on COX-2, VEGF expression, MMP-9 activity and PGE(2) release in HT-29 cells. These results suggest that adrenaline stimulates cell proliferation of HT-29 cells via both β(1)- and β(2)-adrenoceptors by a COX-2 dependent pathway. Copyright © 2011 Elsevier Inc. All rights reserved.

  2. Mutants of human colon adenocarcinoma, selected for thymidylate synthase deficiency

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    Houghton, P.J.; Germain, G.S.; Hazelton, B.J.; Pennington, J.W.; Houghton, J.A. (Saint Jude Children' s Research Hospital, Memphis, TN (USA))

    1989-02-01

    GC{sub 3}/c1 human colon adenocarcinoma cells were treated with the mutagen ethyl methane sulfonate, and three clones deficient in thymidylate synthase activity were selected and characterized. Growth in medium deficient in thymidine caused cell death in two clones (TS{sup {minus}}c{sub 1} and TS{sup {minus}}c{sub 3}), whereas one clone (TS{sup {minus}}c{sub 2}) showed limited growth. Growth correlated with thymidine synthase activity and 5-fluoro-2{prime}-deoxyuridine 5{prime}-monophosphate-binding capacity and with incorporation of 2{prime}-deoxy(6-{sup 3}H)uridine into DNA. In the presence of optimal thymidine, growth rates were only 5-18% that of the parental clone (GC{sub 3}/c1), which grew equally well in thymidine-deficient or -replete medium. Analysis of poly(A){sup +} RNA showed normal levels of a 1.6-kilobase transcript in TS{sup {minus}}c{sub 1} and TS{sup minus}c{sub 2} but decreased levels in TS{sup {minus}}c{sub 3}. Clone TS{sup minus}c{sub 3} was 32-, 750-, and >100,000-fold more resistant than the parental clone to 5-fluorouracil, 5-fluoro-2{prime}-deoxyuridine, and methotrexate, respectively. When inoculated into athymic nude mice, each TS{sup {minus}} clone produced tumors, demonstrating continued ability to proliferate in vivo.

  3. Sex difference in cellular retinol- and retinoic acid-binding proteins in human colon adenocarcinomas.

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    Palan, P R; Duttagupta, C; Romney, S L

    1980-12-01

    Human colon adenocarcinomas and adjacent non-cancerous, normal colon from the same patient were assayed for the presence and amounts of cellular binding proteins for retinol (CRBP) and retinoic acid (CRABP) by sucrose gradient analysis. In male patients, the mean concentrations of both CRBP and CRABP in the colon cancers were statistically significantly higher than in the adjacent normal colon. By contrast, in female colon cancers, the mean levels for both binding proteins were reduced approximately 2-fold, compared to the concentrations in the adjacent normal colon. These findings reveal an unexpected sex difference in the binding proteins for retinol and retinoic acid in human colon malignancies.

  4. Mucinous adenocarcinoma of colon

    National Research Council Canada - National Science Library

    Zamir, Naima; Ahmed, Soofia; Akhtar, Jamshed

    2010-01-01

    .... Underlying colorectal carcinoma is a rare cause and carries a poor prognosis. We report two cases of mucinous adenocarcinoma of colon, one in a 9 years old male and other in a female of 12 years...

  5. Mucinous Adenocarcinoma of Colon

    OpenAIRE

    Jamshed Akhtar; Soofia Ahmed; Naima Zamir

    2010-01-01

    Bleeding per rectum is a common complaint in pediatric age group and mostly relates to benign conditions. Underlying colorectal carcinoma is a rare cause and carries a poor prognosis. We report two cases of mucinous adenocarcinoma of colon, one in a 9 years old male and other in a female of 12 years. The boy presented with rectal bleeding and increasing constipation of more than three years duration. He had mucinous adenocarcinoma (T3N0MX) of rectosigmoid region and underwent local complete r...

  6. Different molecular organization of two carotenoids, lutein and zeaxanthin, in human colon epithelial cells and colon adenocarcinoma cells

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    Grudzinski, Wojciech; Piet, Mateusz; Luchowski, Rafal; Reszczynska, Emilia; Welc, Renata; Paduch, Roman; Gruszecki, Wieslaw I.

    2018-01-01

    Two cell lines, human normal colon epithelial cells (CCD 841 CoTr) and human colon adenocarcinoma cells (HT-29) were cultured in the presence of exogenous carotenoids, either zeaxanthin or lutein. Both carotenoids demonstrated cytotoxicity with respect to cancer cells but not to normal cells. Cells from both the cell lines were analyzed with application of fluorescence lifetime imaging microscopy and Raman scattering microscopy. Both imaging techniques show effective incorporation of carotenoid molecules into growing cells. Comparison of the Raman scattering and fluorescence lifetime characteristics reveals different molecular organization of carotenoids in the carcinoma and normal cells. The main difference consists in a carotenoid aggregation level which is substantially lower in the carcinoma cells as compared to the normal cells. Different molecular organization of carotenoids was interpreted in terms of a different metabolism of normal and carcinoma cells and has been concluded to provide a possibility of cancer diagnosis based on spectroscopic analyses.

  7. Subcellular distribution and expression of cofilin and ezrin in human colon adenocarcinoma cell lines with different metastatic potential

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    D. Nowak

    2010-04-01

    Full Text Available The dynamic reorganization of the actin cytoskeleton is regulated by a number of actin binding proteins (ABPs. Four human colon adenocarcinoma cell lines – parental and three selected sublines, which differ in motility and metastatic potential, were used to investigate the expression level and subcellular localization of selected ABPs. Our interest was focused on cofilin and ezrin. These proteins are essential for cell migration and adhesion. The data received for the three more motile adenocarcinoma sublines (EB3, 3LNLN, 5W were compared with those obtained for the parental LS180 adenocarcinoma cells and fibroblastic NRK cells. Quantitative densitometric analysis and confocal fluorescence microscopy were used to examine the expression levels and subcellular distribution of the selected ABPs. Our data show distinct increase in the level of cofilin in adenocarcinoma cells accompanied by the reduction of inactive phosphorylated form of cofilin. In more motile cells, cofilin was accumulated at cellular periphery in co-localization with actin filaments. Furthemore, we indicated translocation of ezrin towards the cell periphery within more motile cells in comparison with NRK and parental adenocarcinoma cells. In summary, our data indicate the correlation between migration ability of selected human colon adenocarcinoma sublines and subcellular distribution as well as the level of cofilin and ezrin. Therefore these proteins might be essential for the higher migratory activity of invasive tumor cells.

  8. Cytotoxic and apoptotic effects of chalcone derivatives of 2-acetyl thiophene on human colon adenocarcinoma cells.

    Science.gov (United States)

    de Vasconcelos, Alana; Campos, Vinicius Farias; Nedel, Fernanda; Seixas, Fabiana Kömmling; Dellagostin, Odir A; Smith, Kevin R; de Pereira, Cláudio Martin Pereira; Stefanello, Francieli Moro; Collares, Tiago; Barschak, Alethéa Gatto

    2013-06-01

    Recent studies report that chalcones exhibit cytotoxicity to human cancer cell lines. Typically, the form of cell death induced by these compounds is apoptosis. In the context of the discovery of new anticancer agents and in light of the antitumour potential of several chalcone derivatives, in the present study, we synthesized and tested the cytotoxicity of six chalcone derivatives on human colon adenocarcinoma cells. Six derivatives of 3-phenyl-1-(thiophen-2-yl) prop-2-en-1-one were prepared and characterized on the basis of their (1) H and (13) C NMR spectra. HT-29 cells were treated with synthesized chalcones on two concentrations by three different incubation times. Cells were evaluated by cell morphology, Tetrazolium dye (MTT) colorimetric assay, live/dead, flow cytometry (annexin V) and gene expression analyses to determine the cytotoxic way. Chalcones 3-(4-bromophenyl)-1-(thiophen-2-yl)prop-2-en-1-one (C06) and 3-(2-nitrophenyl)-1-(thiophen-2-yl)prop-2-en-1-one (C09) demonstrated higher cytotoxicity than other chalcones as shown by cell morphology, live/dead and MTT assays. In addition, C06 induced apoptosis on flow cytometry annexin V assay. These data were confirmed by a decreased expression of anti-apoptotic genes and increased pro-apoptotic genes. Our findings indicate in summary that the cytotoxic activity of chalcone C06 on colorectal carcinoma cells occurs by apoptosis. Copyright © 2012 John Wiley & Sons, Ltd.

  9. Size- and dose-dependent toxicity of cellulose nanocrystals (CNC) on human fibroblasts and colon adenocarcinoma.

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    Hanif, Zahid; Ahmed, Farrukh R; Shin, Seung Won; Kim, Young-Kee; Um, Soong Ho

    2014-07-01

    A controlled preparation of cellulose nanocrystals of different sizes and shapes has been carried out by acid hydrolysis of microcrystalline cellulose. The size- and concentration-dependent toxicity effects of the resulting cellulose nanocrystals were evaluated against two different cell lines, NIH3T3 murine embryo fibroblasts and HCT116 colon adenocarcinoma. It could serve as a therapeutic platform for cancer treatment. Copyright © 2014 Elsevier B.V. All rights reserved.

  10. Silver nanoparticles: Antibacterial activity against wound isolates & invitro cytotoxic activity on Human Caucasian colon adenocarcinoma

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    J. Saraniya Devi

    2012-05-01

    Full Text Available Objective: To synthesize the silver nanoparticles (AgNPs using the extracts of Hypnea sp. and to investigate the antibacterial activity against Eshcherichia coli, Staphylococcus aureus and invitro cytotoxic activity on HT-29. Methods: In the present study, AgNPs were synthesized using the aqueous extract of marine macro-algae, and were characterized using UV-visible spectroscopy, Fourrier Transform Infra red (FT-IR spectroscopy, X-ray diffraction (XRD analysis and Transmission Electron Microscopy (TEM analysis. Further these synthesized AgNPs were evaluated for their antibacterial activity with the clinical isolates from wound specimens. The isolates were characterized by different tests viz., microscopical observation, colony morphology, biochemical & sugar fermentation tests. The synthesized AgNPs were tested for its antibacterial activity against the isolates by agar well diffussion method. The AgNPs were assessesd for its cytotoxic activity on Human Caucasian colon adenocarcinoma (HT-29 cell lines. Results: In this study, it is clear that the synthesized AgNPs were spherical measuring 10-20nm and was found to be more bactericidal against Gram-negative bacteria (E. coli than Gram-positive bacteria (Staphylococcus aureus isolated from wound specimen. The invitro screening of the AgNPs showed potential cytotoxic activity against the colon cancer cell lines. Conclusions: Proteins can bind to nanoparticles either through the electrostatic attraction of negatively charged carboxylate groups in Hypnea sp. and stabilization of the AgNPs by protein occurs. The antimicrobial activities of AgNPs are influenced by the dimensions of the particles the smaller the particles, the greater antimicrobial effect. The cytotoxic activity may be due to the presence of alkaloids present in the Hypnea sp.

  11. A Potential Daidzein Derivative Enhances Cytotoxicity of Epirubicin on Human Colon Adenocarcinoma Caco-2 Cells

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    Yu-Li Lo

    2012-12-01

    Full Text Available In this study, we evaluated the effects of 8-hydroxydaidzein (8HD, an isoflavone isolated from fermented soy germ koji, and epirubicin (Epi, an antineoplastic agent, on the production of reactive oxygen species (ROS. We subsequently correlated the ROS levels to the anticancer mechanisms of Epi and 8HD in human colon adenocarcinoma Caco-2 cells. 8HD enhanced cytotoxicity of Epi and generated a synergistic effect. Epi and/or 8HD treatments increased the hydrogen peroxide and superoxide levels. Combined treatment markedly decreased mRNA expression levels of multidrug resistance protein 1 (MDR1, MDR-associated protein (MRP 1, and MRP2. 8HD significantly intensified Epi intracellular accumulation in Caco-2 cells. 8HD and/or Epi-induced apoptosis, as indicated by the reduced mitochondrial membrane potential and increased sub-G1 phase in cell cycle. Moreover, 8HD and Epi significantly enhanced the mRNA expressions of Bax, p53, caspases-3, -8, and -9. To our best knowledge, this study verifies for the first time that 8HD effectively circumvents MDR in Caco-2 cells through the ROS-dependent inhibition of efflux transporters and p53-mediated activation of both death receptor and mitochondrial pathways of apoptosis. Our findings of 8HD shed light on the future search for potential biotransformed isoflavones to intensify the cytotoxicity of anticancer drugs through simultaneous reversal of pump and nonpump resistance.

  12. Neurological manifestation of colonic adenocarcinoma

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    Uzair Chaudhary

    2012-04-01

    Full Text Available Paraneoplastic neurologic disorders are extremely rare in cancer patients and are most commonly associated with certain tumors, such as ovarian cancer, small cell lung cancer, and breast cancer. We report here a paraneoplastic neurological syndrome in a 53-year-old man with colonic adenocarcinoma with a solitary liver metastasis. His paraneoplastic syndrome was successfully treated by methylprednisolone and primary oncologic therapies including neoadjuvant chemotherapy and definitive surgery. This is also the first documented case of simultaneous manifestation of a sensory neuropathy and limbic encephalitis with colon cancer.

  13. A human colon adenocarcinoma xenograft--radiation response, cellular composition, and tumor disaggregation.

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    West, C M; Keng, P C; Siemann, D W; Sutherland, R M

    1987-02-01

    The human colon adenocarcinoma cell line WiDr was xenografted and the tumor characterized. When athymic mice (NCR-nu) were inoculated with 10(6) cells, tumors appeared after 7-14 days with a 93-100% take rate and grew with an initial volume-doubling time of around 6 days. For optimizing the tumor disaggregation method, a comparison was made of two dissociation procedures and of different dissociation times. An enzyme cocktail (collagenase, DNase, pronase) resulted in total viable cell yields of 1-3 X 10(7) cells/g tumor tissue. Cell yield decreased with increasing tumor weight. Disaggregation with trypsin gave lower cell yields; and so, although the plating efficiencies (PEs) were higher, the enzyme cocktail was chosen for tumor disaggregation. On the basis of morphologic identification, cell suspensions prepared from WiDr tumors, by use of the enzyme cocktail for 2 hours, contained 49% malignant cells as well as a significant fraction of nonneoplastic cells. The major nonneoplastic host cell component was macrophage (33%); lymphocytes (13%) and granulocytes (5%) also were present. Host cells could be separated from neoplastic cells by centrifugal elutriation. By mixing various proportions of host and tumor cells, it was subsequently shown that the presence of host cells did not influence the malignant cell PE unless the cell suspensions contained greater than 90% host cells. Single-cell suspensions prepared from WiDr tumors, with use of the enzyme cocktail for 2 hours, were irradiated and then plated for survival (D0 = 1.5 Gy; n = 5) (D0, the 37% dose slope). A comparison was made of the sensitivity to radiation, after the different dissociation methods. The radiation sensitivities after 1.5-hour trypsinization and 2- and 6-hour enzyme cocktail administrations were similar, but after 0.5 hour of trypsin, the cells were more sensitive to radiation.

  14. Iron overload of human colon adenocarcinoma cells studied by synchrotron-based X-ray techniques

    NARCIS (Netherlands)

    Mihucz, Victor G.; Meirer, Florian; Polgári, Zsófia; Réti, Andrea; Pepponi, Giancarlo; Ingerle, Dieter; Szoboszlai, Norbert; Streli, Christina

    2016-01-01

    Fast- and slow-proliferating human adenocarcinoma colorectal cells, HT-29 and HCA-7, respectively, overloaded with transferrin (Tf), Fe(III) citrate, Fe(III) chloride and Fe(II) sulfate were studied by synchrotron radiation total-reflection X-ray spectrometry (TXRF), TXRF-X-ray absorption near edge

  15. Short-Chain Fatty Acids Stimulate Angiopoietin-Like 4 Synthesis in Human Colon Adenocarcinoma Cells by Activating Peroxisome Proliferator-Activated Receptor γ

    DEFF Research Database (Denmark)

    Alex, Sheril; Lange, Katja; Amolo, Tom

    2013-01-01

    with the notion that fermentation leads to PPAR activation in vivo, feeding mice a diet rich in inulin induced PPAR target genes and pathways in the colon. We conclude that (i) SCFA potently stimulate ANGPTL4 synthesis in human colon adenocarcinoma cells and (ii) SCFA transactivate and bind to PPARγ. Our data...

  16. Normalizing genes for quantitative RT-PCR in differentiating human intestinal epithelial cells and adenocarcinomas of the colon.

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    Dydensborg, Anders Bondo; Herring, Elizabeth; Auclair, Joëlle; Tremblay, Eric; Beaulieu, Jean-Francois

    2006-05-01

    As for other mRNA measurement methods, quantitative RT-PCR results need to be normalized relative to stably expressed genes. Widely used normalizing genes include beta-actin and glyceraldehyde-3-phosphate dehydrogenase. It has, however, become clear that these and other normalizing genes can display modulated patterns of expression across tissue types and during complex cellular processes such as cell differentiation and cancer progression. Our objective was to set the basis for identifying normalizing genes that displayed stable expression during enterocytic differentiation and between healthy tissue and adenocarcinomas of the human colon. We thus identified novel potential normalizing genes using previously generated cDNA microarray data and examined the alterations of expression of two of these genes as well as seven commonly used normalizing genes during the enterocytic differentiation process and between matched pairs of resection margins and primary carcinomas of the human colon using real-time RT-PCR. We found that ribosomal phosphoprotein P0 was particularly stable in all intestinal epithelial cell extracts, thereby representing a particularly robust housekeeping reference gene for the assessment of gene expression during the human enterocytic differentiation process. On the other hand, beta-2-microglobulin generated the best score as a normalizing gene for comparing human colon primary carcinomas with their corresponding normal mucosa of the resection margin, although others were found to represent acceptable alternatives. In conclusion, we identified and characterized specific normalizing genes that should significantly improve quantitative mRNA studies related to both the differentiation process of the human intestinal epithelium and adenocarcinomas of the human colon. This approach should also be useful to validate normalizing genes in other intestinal contexts.

  17. Scaffold-Free Coculture Spheroids of Human Colonic Adenocarcinoma Cells and Normal Colonic Fibroblasts Promote Tumorigenicity in Nude Mice

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    Jong-il Park

    2016-02-01

    Full Text Available The aim of this study was to form a scaffold-free coculture spheroid model of colonic adenocarcinoma cells (CACs and normal colonic fibroblasts (NCFs and to use the spheroids to investigate the role of NCFs in the tumorigenicity of CACs in nude mice. We analysed three-dimensional (3D scaffold-free coculture spheroids of CACs and NCFs. CAC Matrigel invasion assays and tumorigenicity assays in nude mice were performed to examine the effect of NCFs on CAC invasive behaviour and tumorigenicity in 3D spheroids. We investigated the expression pattern of fibroblast activation protein-α (FAP-α by immunohistochemical staining. CAC monocultures did not form densely-packed 3D spheroids, whereas cocultured CACs and NCFs formed 3D spheroids. The 3D coculture spheroids seeded on a Matrigel extracellular matrix showed higher CAC invasiveness compared to CACs alone or CACs and NCFs in suspension. 3D spheroids injected into nude mice generated more and faster-growing tumors compared to CACs alone or mixed suspensions consisting of CACs and NCFs. FAP-α was expressed in NCFs-CACs cocultures and xenograft tumors, whereas monocultures of NCFs or CACs were negative for FAP-α expression. Our findings provide evidence that the interaction between CACs and NCFs is essential for the tumorigenicity of cancer cells as well as for tumor propagation.

  18. N-Hydroxycinnamide derivatives of osthole presenting genotoxicity and cytotoxicity against human colon adenocarcinoma cells in vitro and in vivo.

    Science.gov (United States)

    Liu, Ling-Yu; Huang, Wei-Jan; Lin, Ren-Jye; Lin, Shyr-Yi; Liang, Yu-Chih

    2013-11-18

    Osthole is extracted from the Chinese herbs Cnidium monnieri and Angelica pubescens, and it was found to have antitumor activity in vitro and in vivo. A series of osthole derivatives have been synthesized, and the N-hydroxycinnamide derivatives of osthole, WJ1376-1 and WJ1398-1 were found to have the greatest potential against human colon adenocarcinoma cells. In contrast to the parental osthole, both WJ1376-1 and WJ1398-1 were found to induce multinucleation and polyploidy by microscopic observation and flow cytometry. WJ1376-1 and WJ1398-1 significantly activated ataxia telangiectasia and rad3 related (ATR) kinase, which triggered activation of the checkpoint kinase 2 (Chk2) signaling pathway and then down regulated Cdc25 phosphatase and Cdc2/cyclin B kinase activities. WJ1376-1 and WJ1398-1 also inhibited the phosphorylation of Aurora A kinase, which is associated with important processes during mitosis. The presence of a "comet" DNA fragment and phosphorylation of p53 at Ser 15 clearly indicated that DNA damage occurred with WJ1376-1 and WJ1398-1 treatment. WJ1376-1 and WJ1398-1 ultimately induced apoptosis as evidenced by the upregulation of Bad and activation of caspases-3, -7, and -9. Furthermore, WJ1376-1 and WJ1398-1 also showed a great effect in attenuating tumor growth without affecting the body weight of xenograft nude mice. Taken together, these results suggest that the toxic activities of WJ1376-1 and WJ1398-1 were dissimilar to that of the parental osthole, which can induce cell polyploidy and G2/M cell cycle arrest in colon adenocarcinoma cells and may provide a potential therapeutic target for colon cancer treatment in the future.

  19. De novo expression of human polypeptide N-acetylgalactosaminyltransferase 6 (GalNAc-T6) in colon adenocarcinoma inhibits the differentiation of colonic epithelium

    DEFF Research Database (Denmark)

    Lavrsen, Kirstine; Dabelsteen, Sally; Vakhrushev, Sergey Y

    2017-01-01

    investigated the expression patterns of all of the GalNAc-Ts in colon cancer by analysing transcriptomic data. We found that GalNAc-T6 was highly upregulated in colon adenocarcinomas but absent in normal-appearing adjacent colon tissue. The results were verified by immunohistochemistry, suggesting that Gal...... that this isoform has unique cellular functions. In support of this notion, the genetically and functionally closely related GalNAc-T3 homologue did not shown compensatory functionality for effects observed for GalNAc-T6. Taken together, these data strongly suggest that aberrant GalNAc-T6 expression and site......-specific glycosylation is involved in oncogenic transformation....

  20. Antioxidant potential of buffalo and cow milk Cheddar cheeses to tackle human colon adenocarcinoma (Caco-2 cells

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    Nuzhat Huma

    2018-02-01

    Full Text Available Objective The aim of present study was to assess the anti-oxidant potential of water-soluble peptides (WSPs extract derived from buffalo and cow milk Cheddar cheeses at different stages of ripening. Methods The antioxidant potential of WSPs extract was assessed through 2,2’-azinobis-3-ethylbenzothiazoline-6sulfonic acid (ABTS-radical scavenging activity. In addition, impact of WSPs extract on cell viability and production of reactive oxygen species (ROS in human colon adenocarcinoma Caco-2 (tert-butylhydroperoxide-induced cell lines was also evaluated. Results The ABTS-radical scavenging activity increased progressively with ripening period and dose-dependently in both cheeses. However, peptide extract from buffalo milk Cheddar cheese demonstrated relatively higher activity due to higher contents of water-soluble nitrogen. Intracellular ROS production in Caco-2 cells decreased significantly (p<0.05 till 150th day of cheese ripening and remained constant thereafter. Additionally, dose-dependent response of WSPs extract on antioxidant activity was noticed in the Caco-2 cell line. Conclusion On the basis of current in vitro study, the Cheddar cheese WSPs extract can protect intestinal epithelium against oxidative stress due to their antioxidant activity.

  1. Uptake and cytotoxicity of poly(D,L-lactide-co-glycolide) nanoparticles in human colon adenocarcinoma cells

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    Katsikari, A. [Laboratory of General Microbiology, Department of Genetics, Development and Molecular Biology, School of Biology, Faculty of Sciences and Mathematics, Aristotle University of Thessaloniki, Thessaloniki 54124 (Greece); Patronidou, Chr.; Kiparissides, C. [Section of Analysis, Design and Control of Chemical Processes and Plants, Department of Chemical Engineering, Aristotle University of Thessaloniki, Thessaloniki 54124 (Greece); Arsenakis, M., E-mail: arsenaki@bio.auth.g [Laboratory of General Microbiology, Department of Genetics, Development and Molecular Biology, School of Biology, Faculty of Sciences and Mathematics, Aristotle University of Thessaloniki, Thessaloniki 54124 (Greece)

    2009-12-15

    The main objectives of the present study were to evaluate the cytotoxicity and the mechanisms of uptake of biodegradable lactic acid-glycolic acid copolymer (PLGA) nanoparticle carrier systems in vitro using the human colon adenocarcinoma cell line Caco2. Nanoparticles (NPs) (PLGA 75:25) with an average diameter of 299.5 nm containing bovine serum albumin labeled with fluorescein isothiocyanate (BSA-FITC) as a fluorescent model protein marker were formulated by the double emulsion technique. Various parameters influencing the internalization process by Caco2 cells including concentration of NPs, duration of contact time and cell culture conditions were studied. After overnight exposure of NPs to cells at 37 deg. C, the cell uptake capacity varied in accord with NP concentration, over the 25-800 mug/ml concentration range tested. Maximal uptake of nanoparticles at 37 deg. C occurred at 4 h and was inhibited significantly at 4 deg. C. The extent of NPs internalization was evaluated by confocal laser scanning microscopy. Potential NP toxicity evaluated by modified MTS and lactate dehydrogenase (LDH) colorimetric cytotoxicity tests, measuring mitochondrial activity and membrane integrity respectively, showed that cell viability is significantly reduced at PLGA nanoparticle concentrations greater than 700 mug/ml after 24 and 48 h respectively. The results obtained in vitro for BSA-FITC loaded PLGA nanoparticles underline their potential as carriers for peptide delivery and their utility for the study of NP cell transport and trafficking mechanisms.

  2. Adenocarcinoma of the colon in a child.

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    Shah R

    1992-04-01

    Full Text Available A rare case of a 10 year old boy presenting with history of lower GI bleeding for one year and acute intestinal obstruction was diagnosed as adenocarcinoma of the colon on exploration. One year follow-up after radical colectomy did not show any recurrence.

  3. Curcumin inhibits growth potential by G1 cell cycle arrest and induces apoptosis in p53-mutated COLO 320DM human colon adenocarcinoma cells.

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    Dasiram, Jade Dhananjay; Ganesan, Ramamoorthi; Kannan, Janani; Kotteeswaran, Venkatesan; Sivalingam, Nageswaran

    2017-02-01

    Curcumin, a natural polyphenolic compound and it is isolated from the rhizome of Curcuma longa, have been reported to possess anticancer effect against stage I and II colon cancer. However, the effect of curcumin on colon cancer at Dukes' type C metastatic stage III remains still unclear. In the present study, we have investigated the anticancer effects of curcumin on p53 mutated COLO 320DM human colon adenocarcinoma cells derived from Dukes' type C metastatic stage. The cellular viability and proliferation were assessed by trypan blue exclusion assay and MTT assay, respectively. The cytotoxicity effect was examined by lactate dehydrogenase (LDH) cytotoxicity assay. Apoptosis was analyzed by DNA fragmentation analysis, Hoechst and propidium iodide double fluorescent staining and confocal microscopy analysis. Cell cycle distribution was performed by flow cytometry analysis. Here we have observed that curcumin treatment significantly inhibited the cellular viability and proliferation potential of p53 mutated COLO 320DM cells in a dose- and time-dependent manner. In addition, curcumin treatment showed no cytotoxic effects to the COLO 320DM cells. DNA fragmentation analysis, Hoechst and propidium iodide double fluorescent staining and confocal microscopy analysis revealed that curcumin treatment induced apoptosis in COLO 320DM cells. Furthermore, curcumin caused cell cycle arrest at the G1 phase, decreased the cell population in the S phase and induced apoptosis in COLO 320DM colon adenocarcinoma cells. Together, these data suggest that curcumin exerts anticancer effects and induces apoptosis in p53 mutated COLO 320DM human colon adenocarcinoma cells derived from Dukes' type C metastatic stage. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  4. Distribution of individual components of basement membrane in human colon polyps and adenocarcinomas as revealed by monoclonal antibodies

    DEFF Research Database (Denmark)

    Ljubimov, A V; Bartek, J; Couchman, J R

    1992-01-01

    by the presence of fibrillar deposits of basement-membrane components, mainly of collagen type IV and/or heparan sulfate proteoglycan. This reaction was never observed in polyps and may be derived from myofibroblasts reported to accumulate in colon cancer stroma. The combined use of antibodies to basement......-membrane components (laminin, entactin/nidogen, collagen type IV and large heparan sulfate proteoglycan), as well as to keratin 8. In all adenocarcinomas, including mucinous, basement membranes were altered more at the invasive front than in the parenchyma. The degree of this alteration was inversely correlated...

  5. Sulforaphane down-regulates SKP2 to stabilize p27(KIP1) for inducing antiproliferation in human colon adenocarcinoma cells.

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    Chung, Yuan-Kai; Chi-Hung Or, Richard; Lu, Chien-Hsing; Ouyang, Wei-Ting; Yang, Shu-Yi; Chang, Chia-Che

    2015-01-01

    Sulforaphane is a cruciferous vegetable-derived isothiocyanate with promising chemopreventive and therapeutic activities. Induction of proliferation arrest and apoptosis principally contribute to sulforaphane's anticancer activity, but the precise molecular mechanisms remain elusive. The oncoprotein SKP2 is a key component of the SKP1-CULLIN1-F-box (SCF) E3 ligase complex and is responsible for directing SCF-mediated degradation of cyclin-dependent kinase inhibitor p27(KIP1) to promote cell proliferation. We herein provide the first evidence supporting the critical involvement of the SKP2-p27(KIP1) axis in sulforaphane-induced antiproliferation in various human colon adenocarcinoma cell lines. Specifically, sulforaphane markedly suppressed the levels of bromodeoxyuridine (BrdU) incorporation and clonogenicity in all tested cell lines, illustrating the antiproliferative effect of sulforaphane. Of note, sulforaphane-induced antiproliferation was accompanied with down-regulation of SKP2, leading to the stabilization and thus up-regulation of p27(KIP1). Additionally, sulforaphane was found to down-regulate SKP2 mainly through transcriptional repression, as sulforaphane lowered SKP2 mRNA expression and the SKP2 promoter activity. Furthermore, sulforaphane treatment led to the activation of both AKT and ERK, thus ruling out the possibility that sulforaphane down-regulates SKP2 by inhibiting AKT or ERK. Notably, sulforaphane-elicited suppression of BrdU incorporation and clonogenicity were significantly rescued in the context of SKP2 overexpression or p27(KIP1) depletion, therefore highlighting the important role of SKP2 down-regulation and the ensuing stabilization of p27(KIP1) in sulforaphane-induced antiproliferation. Collectively, these data expand our molecular understanding about how sulforaphane elicits proliferation arrest, but also implicate the application of sulforaphane in therapeutic modalities targeting SKP2. Copyright © 2014 The Society for Biotechnology

  6. In vitro anti-cancer activities of Job's tears (Coix lachryma-jobi Linn.) extracts on human colon adenocarcinoma.

    Science.gov (United States)

    Manosroi, Aranya; Sainakham, Mathukorn; Chankhampan, Charinya; Manosroi, Worapaka; Manosroi, Jiradej

    2016-03-01

    The whole seed (W), endosperm (E) and hull (H) of five cultivars of Job's tears (Coix lachryma-jobi Linn. var. ma-yuen Stapf) including Thai Black Phayao, Thai Black Loei, Laos Black Loei, Laos White Loei and Laos Black Luang Phra Bang were processed before solvent extraction by non-cooking, roasting, boiling and steaming Each part of the Job's tears was extracted by the cold and hot process by refluxing with methanol and hexane. The total of 330 extracts included 150 methanol extracts and 180 hexane extracts were investigated for anti-proliferative activity on human colon adenocarcinoma cell line (HT-29) by the sulforhodamine B (SRB) assay. The extracts which gave high anti-proliferative activity were tested for apoptotic activity by acridine orange and ethidium bromide double staining and anti-oxidative activities including free radical scavenging and lipid peroxidation inhibition activities. The extract from the hull of Thai Black Loei roasted before extracting by hot methanol (M-HTBL-R2) showed the highest anti-proliferative activity on HT-29 with the IC50 values of 11.61 ± 0.95 μg/ml, while the extract from the non-cooked hull of Thai Black Loei by cold methanol extraction (M-HTBL-N1) gave the highest apoptosis (8.17 ± 1.18%) with no necrosis. In addition, M-HTBL-R2 and M-HTBL-N1 indicated free radical scavenging activity at the SC50 values of 0.48 ± 0.12 and 2.47 ± 1.15 mg/ml, respectively. This study has demonstrated the anti-colorectal cancer potential of the M-HTBL-R2 and M-HTBL-N1 extracts.

  7. Binase Immobilized on Halloysite Nanotubes Exerts Enhanced Cytotoxicity toward Human Colon Adenocarcinoma Cells

    Directory of Open Access Journals (Sweden)

    Vera Khodzhaeva

    2017-09-01

    Full Text Available Many ribonucleases (RNases are considered as promising tools for antitumor therapy because of their selective cytotoxicity toward cancer cells. Binase, the RNase from Bacillus pumilus, triggers apoptotic response in cancer cells expressing RAS oncogene which is mutated in a large percentage of prevalent and deadly malignancies including colorectal cancer. The specific antitumor effect of binase toward RAS-transformed cells is due to its direct binding of RAS protein and inhibition of downstream signaling. However, the delivery of proteins to the intestine is complicated by their degradation in the digestive tract and subsequent loss of therapeutic activity. Therefore, the search of new systems for effective delivery of therapeutic proteins is an actual task. This study is aimed to the investigation of antitumor effect of binase immobilized on natural halloysite nanotubes (HNTs. Here, we have developed the method of binase immobilization on HNTs and optimized the conditions for the enzyme loading and release (i; we have found the non-toxic concentration of pure HNTs which allows to distinguish HNTs- and binase-induced cytotoxic effects (ii; using dark-field and fluorescent microscopy we have proved the absorption of binase-loaded HNTs on the cell surface (iii and demonstrated that binase-halloysite nanoformulations possessed twice enhanced cytotoxicity toward tumor colon cells as compared to the cytotoxicity of binase itself (iv. The enhanced antitumor activity of biocompatible binase-HNTs complex confirms the advisability of its future development for clinical practice.

  8. Synchronous Occurrence of Colon and Appendiceal Adenocarcinoma

    OpenAIRE

    Goryń Tomasz; Meszka Monika; Pawlak Jacek

    2014-01-01

    The study presented two cases of synchronous occurrence of colon and appendiceal adenocarcinoma. Both patients required surgical intervention, due to acute peritonitis during the course of acute appendicitis. In case of one patient we performed abdominal CT confirming the presence of sigmoid cancer. The patient was subjected to appendectomy and Hartmann’s operation. The second patient underwent an appendectomy, and colonoscopy performed two months later revealed the presence of rectal adenoca...

  9. Colonic adenocarcinoma presenting as hemophagocytic syndrome

    Directory of Open Access Journals (Sweden)

    Murtaza Ali

    2017-01-01

    Full Text Available Hemophagocytic syndrome (hemophagocytic lymphohistiocytosis [HLH] is a rare and potentially fatal disorder characterized by pathological immune activation associated with primary familial disorder, genetic mutation or occurring as a sporadic condition. The later can be secondary to infections, malignancies, or autoimmune diseases. Malignancy-associated HLH is commonly seen in hematological malignancies and rarely with solid organ tumors. We report a case of adenocarcinoma colon presenting as hemophagocytic syndrome. To the best of our knowledge, it is the first case report of HLH secondary to carcinoma colon.

  10. Integrins are not essential for entry of coxsackievirus A9 into SW480 human colon adenocarcinoma cells.

    Science.gov (United States)

    Heikkilä, Outi; Merilahti, Pirjo; Hakanen, Marika; Karelehto, Eveliina; Alanko, Jonna; Sukki, Maria; Kiljunen, Saija; Susi, Petri

    2016-10-18

    Coxsackievirus A9 (CV-A9) is a pathogenic enterovirus type within the family Picornaviridae. CV-A9 infects A549 human epithelial lung carcinoma cells by attaching to the αVβ6 integrin receptor through a highly conserved Arg-Gly-Asp (RGD) motif, which is located at the exposed carboxy-terminus of the capsid protein VP1 detected in all studied clinical isolates. However, genetically-modified CV-A9 that lacks the RGD motif (CV-A9-RGDdel) has been shown to be infectious in some cell lines but not in A549, suggesting that RGD-mediated integrin binding is not always essential for efficient entry of CV-A9. Two cell lines, A549 and SW480, were used in the study. SW480 was the study object for the integrin-independent entry and A549 was used as the control for integrin-dependent entry. Receptor levels were quantitated by cell sorting and quantitative PCR. Antibody blocking assay and siRNA silencing of receptor-encoding genes were used to block virus infection. Peptide phage display library was used to identify peptide binders to CV-A9. Immunofluorescence and confocal microscopy were used to visualize the virus infection in the cells. We investigated the receptor use and early stages of CV-A9 internalization to SW480 human epithelial colon adenocarcinoma cells. Contrary to A549 infection, we showed that both CV-A9 and CV-A9-RGDdel internalized into SW480 cells and that function-blocking anti-αV integrin antibodies had no effect on the binding and entry of CV-A9. Whereas siRNA silencing of β6 integrin subunit had no influence on virus infection in SW480, silencing of β2-microglobulin (β2M) inhibited the virus infection in both cell lines. By using a peptide phage display screening, the virus-binding peptide identical to the N-terminal sequence of HSPA5 protein was identified and shown to block the virus infection in both A549 and SW480 cell lines. HSPA5 was also found to co-localize with CV-A9 at the SW480 cell periphery during the early stages of infection by confocal

  11. Upregulation of Yes-associated protein and transcriptional co-activator with PDZ-binding motif influences the behavior of LOVO human colon adenocarcinoma cells.

    Science.gov (United States)

    Li, Yu; Li, Lan; Zhu, Min; Ye, Limin; Yang, Qian

    2017-10-01

    The present study aimed to investigate the role of Yes-associated protein (YAP) and transcriptional co-activator with PDZ-binding motif (TAZ) in the LOVO human colon adenocarcinoma cell line and explore the underlying mechanisms. First, the expression levels of YAP and TAZ were detected in LOVO cells using reverse-transcription quantitative PCR, and the results suggested that YAP and TAZ were faintly expressed in LOVO cells. To investigate the exact role of YAP and TAZ in LOVO cells, stable YAP- and/or TAZ-overexpressing LOVO cell lines were established using YAP and/or TAZ expression plasmids. An MTT assay and flow cytometry were used to assess cell proliferation and apoptosis, respectively. The results indicated that compared with the control, YAP or TAZ overexpression significantly increased the proliferation ability of LOVO cells, while apoptosis was significantly decreased. Furthermore, the expression of the tumor-associated proteins connective tissue growth factor and cysteine-rich angiogenic inducer 61, which have critical roles in facilitating cancer cell proliferation, migration and invasion, were found to be upregulated following upregulation of YAP and TAZ. In addition, the expression of cell apoptosis-associated protein B-cell lymphoma 2 (Bcl-2) was significantly increased, while Bcl-2-associated X protein and caspase-3 were inhibited by YAP or TAZ overexpression. All of these effects were amplified when YAP and TAZ were co-overexpressed. In conclusion, YAP and TAZ function as tumor promoters in human colon carcinoma, and upregulation of YAP and TAZ influences the behavior of LOVO colon adenocarcinoma cells via regulating tumor-associated gene expression.

  12. [Study of a intestinal enteroliths in human patient with colon adenocarcinoma. Is it similar to renal calculi?].

    Science.gov (United States)

    Traba Villameytide, M L; Orts Costa, J A; Morell, M

    2006-02-01

    This work shows the study performance to intestinal enterolithis from a 91 year old patient with multiple enterolithiasis confirmed by abdominal X-ray and TAC analyses showing the presence of intestinal, renal and bile stones. This enterolithis is associated with colon adenocarcinoma. The enteroliths were obtained by hemicolectomia and were analyzed by infrared spectroscopy (IR), giving non-stoichiometry carbonate apatite whitloquite-like with, possibly, organic material. By atomic emission spectroscopy we found Ca, Mg, K, Na and K (mg/100 mg of calculi) and Zn, Ba, Mn, Fe, Cu, Si, Ti and Br in minor proportion (microg/100 mg of calculi). Because of calculi morphology and the IR spectra (non-stoichiometry carbonate apatite) we carried out analysis by high performance liquid chromatography (HPLC) and found coproporphyrin (about microg/g of calculi) and uroporphyrin, protoporphyrin and heptacarboxy-porphyrin in minor extent. Calculi were also studied by scanning electronic microscopy and EDX and X-ray diffraction giving crystals of CaP4O11. All these results show that intestinal enteroliths composition are similar to renal calculi although its morphology differs from renal calculi.

  13. Clostridium septicum aortitis with synchronous ascending colon and rectal adenocarcinoma

    OpenAIRE

    Jain, Deepanshu; Kistler, Andrew C.; Kozuch, Patricia

    2017-01-01

    Clostridium septicum (C. septicum) aortitis is a rare condition frequently associated with colon adenocarcinoma and carries a poor prognosis. We report the case of a 66-year-old man who presented with abdominal pain, blood in the stool, fever and chills. Laboratory tests were significant for leukocytosis and microcytic anemia. Abdominal imaging revealed a right colon mass and aortitis. Colonoscopy confirmed the right colon mass and also discovered a rectal mass, both adenocarcinomas. Treatmen...

  14. Atypical presentation of colon adenocarcinoma: a case report

    Directory of Open Access Journals (Sweden)

    Tumwine Lynnette K

    2012-02-01

    Full Text Available Abstract Introduction Adenocarcinoma of the colon is the most common histopathological type of colorectal cancer. In Western Europe and the United States, it is the third most common type and accounts for 98% of cancers of the large intestine. In Uganda, as elsewhere in Africa, the majority of patients are elderly (at least 60 years old. However, more recently, it has been observed that younger patients (less than 40 years of age are presenting with the disease. There is also an increase in its incidence and most patients present late, possibly because of the lack of a comprehensive national screening and preventive health-care program. We describe the clinicopathological features of colorectal carcinoma in the case of a young man in Kampala, Uganda. Case presentation A 27-year-old man from Kampala, Uganda, presented with gross abdominal distension, progressive loss of weight, and fever. He was initially screened for tuberculosis, hepatitis, and lymphoma, and human immunodeficiency virus/acquired immunodeficiency syndrome infection. After a battery of tests, a diagnosis of colorectal carcinoma was finally established with hematoxylin and eosin staining of a cell block made from the sediment of a liter of cytospun ascitic fluid, which showed atypical glands floating in abundant extracellular mucin, suggestive of adenocarcinoma. Ancillary tests with alcian blue/periodic acid Schiff and mucicarmine staining revealed that it was a mucinous adenocarcinoma. Immunohistochemistry showed strong positivity with CDX2, confirming that the origin of the tumor was the colon. Conclusions Colorectal carcinoma has been noted to occur with increasing frequency in young adults in Africa. Most patients have mucinous adenocarcinoma, present late, and have rapid disease progression and poor outcome. Therefore, colorectal malignancy should no longer be excluded from consideration only on the basis of a patient's age. A high index of suspicion is important in the

  15. Atypical presentation of colon adenocarcinoma: a case report.

    Science.gov (United States)

    Tumwine, Lynnette K; Kagimu, Magid; Ocama, Ponsiano; Segamwenge, Innocent; Masiira-Mukasa, Noah; Wamala, Dan; Dworak, Otto; Opio, Christopher K

    2012-02-13

    Adenocarcinoma of the colon is the most common histopathological type of colorectal cancer. In Western Europe and the United States, it is the third most common type and accounts for 98% of cancers of the large intestine. In Uganda, as elsewhere in Africa, the majority of patients are elderly (at least 60 years old). However, more recently, it has been observed that younger patients (less than 40 years of age) are presenting with the disease. There is also an increase in its incidence and most patients present late, possibly because of the lack of a comprehensive national screening and preventive health-care program. We describe the clinicopathological features of colorectal carcinoma in the case of a young man in Kampala, Uganda. A 27-year-old man from Kampala, Uganda, presented with gross abdominal distension, progressive loss of weight, and fever. He was initially screened for tuberculosis, hepatitis, and lymphoma, and human immunodeficiency virus/acquired immunodeficiency syndrome infection. After a battery of tests, a diagnosis of colorectal carcinoma was finally established with hematoxylin and eosin staining of a cell block made from the sediment of a liter of cytospun ascitic fluid, which showed atypical glands floating in abundant extracellular mucin, suggestive of adenocarcinoma. Ancillary tests with alcian blue/periodic acid Schiff and mucicarmine staining revealed that it was a mucinous adenocarcinoma. Immunohistochemistry showed strong positivity with CDX2, confirming that the origin of the tumor was the colon. Colorectal carcinoma has been noted to occur with increasing frequency in young adults in Africa. Most patients have mucinous adenocarcinoma, present late, and have rapid disease progression and poor outcome. Therefore, colorectal malignancy should no longer be excluded from consideration only on the basis of a patient's age. A high index of suspicion is important in the diagnosis of colorectal malignancy in young African patients.

  16. Grape waste extract obtained by supercritical fluid extraction contains bioactive antioxidant molecules and induces antiproliferative effects in human colon adenocarcinoma cells.

    Science.gov (United States)

    Lazzè, Maria Claudia; Pizzala, Roberto; Gutiérrez Pecharromán, Francisco Javier; Gatòn Garnica, Paloma; Antolín Rodríguez, Juan Manuel; Fabris, Nicola; Bianchi, Livia

    2009-06-01

    Grape waste management is one of the main problems of winery industries, but, conversely, grape waste contains a high amount of polyphenols that might protect against human diseases related to oxidative stress, such as colorectal cancer. Therefore, the aim of this work was to investigate the antioxidant and antiproliferative activities of a grape waste extract obtained by supercritical fluid extraction. Because the beneficial effect of grape is related to its content of polyphenolic molecules, the extract was chemically characterized by high-performance liquid chromatography in order to assess its major bioactive components. The antioxidant activity of the grape extract was determined. The results showed that the grape extract presents a strong antiradical activity in the in vitro 2,2-diphenyl-1-picrylhydrazyl radical assay and protects against reactive oxygen species production in human colon adenocarcinoma cells (Caco-2). In contrast, the extract did not protect in the citronellal thermooxidation system and showed a weak protective action against lipid peroxidation in Caco-2 cells. The clonogenic assay and the cell cycle distribution analysis showed that the grape extract has a significant antiproliferative effect in a tumor cell line. These data indicate that grape extract is a promising product to be used as an anti-free radical agent and could exert a chemopreventive action.

  17. Comparison of glycoprotein expression between ovarian and colon adenocarcinomas

    DEFF Research Database (Denmark)

    Multhaupt, H A; Arenas-Elliott, C P; Warhol, M J

    1999-01-01

    OBJECTIVE: Tumor-associated antigens may be expressed as surface glycoproteins. These molecules undergo qualitative and quantitative modifications during cell differentiation and malignant transformation. During malignant transformation, incomplete glycosylation is common, and certain glycosylation...... pathways are preferred. These antigens might help distinguish between ovarian and colonic adenocarcinomas in the primary and metastatic lesions. Different cytokeratins have been proposed as relatively organ-specific antigens. DESIGN: We used monoclonal antibodies against T1, Tn, sialosyl-Tn, B72.3, CA125...... in distinguishing between these 2 entities. CONCLUSION: A panel of monoclonal antibodies against cytokeratins 7 and 20 antigens, CA125, and carcinoembryonic antigen is useful in differentiating serous and endometrioid adenocarcinomas of the ovary from colonic adenocarcinomas. Mucinous ovarian adenocarcinomas cannot...

  18. The bioactive potential of red raspberry (Rubus idaeus L.) leaves in exhibiting cytotoxic and cytoprotective activity on human laryngeal carcinoma and colon adenocarcinoma.

    Science.gov (United States)

    Durgo, Ksenija; Belščak-Cvitanović, Ana; Stančić, Angela; Franekić, Jasna; Komes, Draženka

    2012-03-01

    In this article, the bioactive potential of red raspberry leaves, a by-product of this widely spread plant, mostly valued for its antioxidant-rich fruits, was determined. The polyphenolic profile and antioxidative properties of red raspberry leaf extract were determined and examined for potential biological activity. Cytotoxic effect, antioxidative/prooxidative effect, and effect on total glutathione concentration were determined in human laryngeal carcinoma (HEp2) and colon adenocarcinoma (SW 480) cell lines. SW 480 cells are more susceptible to raspberry leaf extract in comparison with HEp2 cells. The antioxidative nature of raspberry leaf extract was detected in HEp2 cells treated with hydrogen peroxide, as opposed to SW 480 cells, where raspberry leaf extract induced reactive oxygen species formation. Raspberry leaf extract increased total glutathione level in HEp2 cells. This effect was reinforced after 24 hours of recovery, indicating that induction was caused by products formed during cellular metabolism of compounds present in the extract. Comparison of the results obtained on these two cell lines indicates that cellular response to raspberry extract will depend on the type of the cells that are exposed to it. The results obtained confirmed the biological activity of red raspberry leaf polyphenols and showed that this traditional plant can supplement the daily intake of valuable natural antioxidants, which exhibit beneficial health effects.

  19. Secondary neoplasms of the larynx from a colonic adenocarcinoma

    DEFF Research Database (Denmark)

    Dadkhah, Naser; Hahn, Christoffer

    2015-01-01

    Secondary neoplasms of the larynx are rare and account for 0.09-0,4% of all laryngeal tumours. Cutaneous melanomas are the preponderant primaries metastasizing to the larynx, fol-lowed by renal cell carcinomas, breast and lung carcinomas. Colonic adenocarcinoma metastases to the larynx are extrem......Secondary neoplasms of the larynx are rare and account for 0.09-0,4% of all laryngeal tumours. Cutaneous melanomas are the preponderant primaries metastasizing to the larynx, fol-lowed by renal cell carcinomas, breast and lung carcinomas. Colonic adenocarcinoma metastases to the larynx...

  20. Combined adenocarcinoma-carcinoid tumor of transverse colon

    OpenAIRE

    Prosanta Kumar Bhattacharjee; Shyamal Halder

    2013-01-01

    A 65-year-old male presented with painless hematochezia associated with episodic cramps in upper abdomen, watery diarrhea, and a slowly growing mass in upper abdomen. Examination revealed a firm 6 x 5 cm, intra-abdominal, epigastric mass. Colonoscopy up to 90 cm showed a stenosing, ulcero-proliferative lesion in the transverse colon. No synchronous lesion was detected. Biopsy revealed mucin secreting adenocarcinoma. Exploration showed the growth involving the transverse colon proximal to the ...

  1. Synchronous Adenocarcinoma of the Colon and Rectal Carcinoid

    Directory of Open Access Journals (Sweden)

    Vamshidhar Vootla

    2016-10-01

    Full Text Available Primary colonic adenocarcinoma and synchronous rectal carcinoids are rare tumors. Whenever a synchronous tumor with a nonmetastatic carcinoid component is encountered, its prognosis is determined by the associate malignancy. The discovery of an asymptomatic gastrointestinal carcinoid during the operative treatment of another malignancy will usually only require resection without additional treatment and will have little effect on the prognosis of the individual. This article reports a synchronous rectal carcinoid in a patient with hepatic flexure adenocarcinoma. We present a case of a 46-year-old Hispanic woman with a history of hypothyroidism, uterine fibroids and hypercholesterolemia presenting with a 2-week history of intermittent abdominal pain, mainly in the right upper quadrant. She had no family history of cancers. Physical examination was significant for pallor. Laboratory findings showed microcytic anemia with a hemoglobin of 6.6 g/dl. CT abdomen showed circumferential wall thickening in the ascending colon near the hepatic flexure and pulmonary nodules. Colonoscopy showed hepatic flexure mass and rectal nodule which were biopsied. Pathology showed a moderately differentiated invasive adenocarcinoma of the colon (hepatic flexure mass and a low-grade neuroendocrine neoplasm (carcinoid of rectum. The patient underwent laparoscopic right hemicolectomy and chemotherapy. In patients diagnosed with adenocarcinoma of the colon and rectum, carcinoids could be missed due to their submucosal location, multicentricity and indolent growth pattern. Studies suggest a closer surveillance of the GI tract for noncarcinoid synchronous malignancy when a carcinoid tumor is detected and vice versa.

  2. In vitro anti-cancer activities of Job’s tears (Coix lachryma-jobi Linn.) extracts on human colon adenocarcinoma

    Science.gov (United States)

    Manosroi, Aranya; Sainakham, Mathukorn; Chankhampan, Charinya; Manosroi, Worapaka; Manosroi, Jiradej

    2015-01-01

    The whole seed (W), endosperm (E) and hull (H) of five cultivars of Job’s tears (Coix lachryma-jobi Linn. var. ma-yuen Stapf) including Thai Black Phayao, Thai Black Loei, Laos Black Loei, Laos White Loei and Laos Black Luang Phra Bang were processed before solvent extraction by non-cooking, roasting, boiling and steaming Each part of the Job’s tears was extracted by the cold and hot process by refluxing with methanol and hexane. The total of 330 extracts included 150 methanol extracts and 180 hexane extracts were investigated for anti-proliferative activity on human colon adenocarcinoma cell line (HT-29) by the sulforhodamine B (SRB) assay. The extracts which gave high anti-proliferative activity were tested for apoptotic activity by acridine orange and ethidium bromide double staining and anti-oxidative activities including free radical scavenging and lipid peroxidation inhibition activities. The extract from the hull of Thai Black Loei roasted before extracting by hot methanol (M-HTBL-R2) showed the highest anti-proliferative activity on HT-29 with the IC50 values of 11.61 ± 0.95 μg/ml, while the extract from the non-cooked hull of Thai Black Loei by cold methanol extraction (M-HTBL-N1) gave the highest apoptosis (8.17 ± 1.18%) with no necrosis. In addition, M-HTBL-R2 and M-HTBL-N1 indicated free radical scavenging activity at the SC50 values of 0.48 ± 0.12 and 2.47 ± 1.15 mg/ml, respectively. This study has demonstrated the anti-colorectal cancer potential of the M-HTBL-R2 and M-HTBL-N1 extracts. PMID:26981007

  3. Integrins are not essential for entry of coxsackievirus A9 into SW480 human colon adenocarcinoma cells

    NARCIS (Netherlands)

    Heikkilä, Outi; Merilahti, Pirjo; Hakanen, Marika; Karelehto, Eveliina; Alanko, Jonna; Sukki, Maria; Kiljunen, Saija; Susi, Petri

    2016-01-01

    Coxsackievirus A9 (CV-A9) is a pathogenic enterovirus type within the family Picornaviridae. CV-A9 infects A549 human epithelial lung carcinoma cells by attaching to the αVβ6 integrin receptor through a highly conserved Arg-Gly-Asp (RGD) motif, which is located at the exposed carboxy-terminus of the

  4. Detection of Cytotoxic Activity of Lectin on Human Colon Adenocarcinoma (Sw480 and Epithelial Cervical Carcinoma (C33-A

    Directory of Open Access Journals (Sweden)

    Mirandeli Bautista

    2011-03-01

    Full Text Available Lectins comprise a heterogeneous class of proteins that recognize the carbohydrate moieties of glycoconjugates with high specificity. Numerous studies have shown that lectins are capable of recognizing specific carbohydrate moieties displayed by malignant cells or tissues. The present work was performed to investigate the effects of tepary bean (Phaseolus acutifolius lectins on proliferation, colony formation, and alteration of DNA synthesis of human malignant cells. Tepary bean lectin showed dose dependent  effects on the inhibition of viability as well as on colony formation in two human malignant cells lines (C33-A, Sw480; By contrast, tepary bean lectin only showed significant effects on DNA synthesis on Sw480 cells. Our results provide evidence of the anti- proliferative and cytotoxic effects of the tepary bean lectins on C33-A and Sw480 cells lines.

  5. Ex vivo characterization of normal and adenocarcinoma colon samples by Mueller matrix polarimetry.

    Science.gov (United States)

    Ahmad, Iftikhar; Ahmad, Manzoor; Khan, Karim; Ashraf, Sumara; Ahmad, Shakil; Ikram, Masroor

    2015-05-01

    Mueller matrix polarimetry along with polar decomposition algorithm was employed for the characterization of ex vivo normal and adenocarcinoma human colon tissues by polarized light in the visible spectral range (425-725 nm). Six derived polarization metrics [total diattenuation (DT ), retardance (RT ), depolarization(ΔT ), linear diattenuation (DL), retardance (δ), and depolarization (ΔL)] were compared for normal and adenocarcinoma colon tissue samples. The results show that all six polarimetric properties for adenocarcinoma samples were significantly higher as compared to the normal samples for all wavelengths. The Wilcoxon rank sum test illustrated that total retardance is a good candidate for the discrimination of normal and adenocarcinoma colon samples. Support vector machine classification for normal and adenocarcinoma based on the four polarization properties spectra (ΔT , ΔL, RT ,and δ) yielded 100% accuracy, sensitivity, and specificity, while both DTa nd DL showed 66.6%, 33.3%, and 83.3% accuracy, sensitivity, and specificity, respectively. The combination of polarization analysis and given classification methods provides a framework to distinguish the normal and cancerous tissues.

  6. Vulvar Villoglandular Adenocarcinoma of Colonic Type: A Rare Finding

    Directory of Open Access Journals (Sweden)

    Heidarali Esmaeili

    2018-01-01

    Full Text Available Colonic type villoglandular adenocarcinoma of the lower genital tract is an extremely rare condition. Its origin is not clearly understood; however, the cloacal remnants are the more accepted source for this carcinoma.We report the case of a 67-year-old female patient who presented with a 1.2 cm polypoidal nodule at the right side of the fourchette. Morphologic studies revealed a colonic type mucinous adenocarcinoma that arose from within a villous adenoma. Immunohistochemical staining showed positive cytokeratin 7, cytokeratin 20, carcinoembryonic antigen, P53, and progesterone receptor, but negative for estrogen receptor and caudal type homeobox transcription factor 2. Extensive work-up failed to reveal other primary cancers in this patient. Ultimately, she underwent a radical vulvectomy. No recurrence was seen in eight months follow up of this patient after surgery. Careful, thorough histological evaluation and clinical clues enable correct diagnosis of the rare colonic type vulvar villoglandular adenocarcinoma. Due to rarity of this tumor, its management is questionable. Therefore, additional investigation is necessary for its management.

  7. Combined adenocarcinoma-carcinoid tumor of transverse colon

    Directory of Open Access Journals (Sweden)

    Prosanta Kumar Bhattacharjee

    2013-01-01

    Full Text Available A 65-year-old male presented with painless hematochezia associated with episodic cramps in upper abdomen, watery diarrhea, and a slowly growing mass in upper abdomen. Examination revealed a firm 6 x 5 cm, intra-abdominal, epigastric mass. Colonoscopy up to 90 cm showed a stenosing, ulcero-proliferative lesion in the transverse colon. No synchronous lesion was detected. Biopsy revealed mucin secreting adenocarcinoma. Exploration showed the growth involving the transverse colon proximal to the splenic flexure with a part of ileum, approximately three feet proximal to ileo-caecal junction, adherent to it. No significant mesenteric lymph node enlargement was evident. The patient underwent resection of the growth along with the segment of adherent ileum. Continuity was re-established by a colo-colic and ileo-ileal anastomosis respectively. Patient received adjuvant chemotherapy. Post-operative histopathology demonstrated a composite histological pattern with an admixture of carcinoid tumor and adenocarcinoma, invasion of ileal serosa and adenocarcinomatous deposits in mesocolic lymph nodes, the tumor staging being (T4, N0, M0/Stage II for carcinoid and (T4, N1, M0/Stage III for adenocarcinoma. Patient was followed-up for a year and was doing well without any evidence of recurrence.

  8. A regulatory network for human adenocarcinoma

    African Journals Online (AJOL)

    AJL

    2012-03-13

    Mar 13, 2012 ... Human adenocarcinoma (AC) is the most frequently diagnosed human lung cancer and its absolute incidence is increasing dramatically. Our study aimed to interpret the mechanisms of human adenocarcinoma through the regulation network based on differentially expressed genes (DEGs). We used the ...

  9. The dietary hydrolysable tannin punicalagin releases ellagic acid that induces apoptosis in human colon adenocarcinoma Caco-2 cells by using the mitochondrial pathway.

    Science.gov (United States)

    Larrosa, Mar; Tomás-Barberán, Francisco A; Espín, Juan Carlos

    2006-09-01

    Polyphenol-rich dietary foodstuffs have attracted attention due to their cancer chemopreventive and chemotherapeutic properties. Ellagitannins (ETs) belong to the so-called hydrolysable tannins found in strawberries, raspberries, walnuts, pomegranate, oak-aged red wine, etc. Both ETs and their hydrolysis product, ellagic acid (EA), have been reported to induce apoptosis in tumour cells. Ellagitannins are not absorbed in vivo but reach the colon and release EA that is metabolised by the human microflora. Our aim was to investigate the effect of a dietary ET [pomegranate punicalagin (PUNI)] and EA on human colon cancer Caco-2 and colon normal CCD-112CoN cells. Both PUNI and EA provoked the same effects on Caco-2 cells: down-regulation of cyclins A and B1 and upregulation of cyclin E, cell-cycle arrest in S phase, induction of apoptosis via intrinsic pathway (FAS-independent, caspase 8-independent) through bcl-XL down-regulation with mitochondrial release of cytochrome c into the cytosol, activation of initiator caspase 9 and effector caspase 3. Neither EA nor PUNI induced apoptosis in normal colon CCD-112CoN cells (no chromatin condensation and no activation of caspases 3 and 9 were detected). In the case of Caco-2 cells, no specific effect can be attributed to PUNI since it was hydrolysed in the medium to yield EA, which entered into the cells and was metabolised to produce dimethyl-EA derivatives. Our study suggests that the anticarcinogenic effect of dietary ETs could be mainly due to their hydrolysis product, EA, which induced apoptosis via mitochondrial pathway in colon cancer Caco-2 cells but not in normal colon cells.

  10. Atypical adenocarcinoma of the colon : radiologic-pathologic correlation

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Young Chan; Ko, Young Tae; Lee, Dong Ho; Yoon, Yup; Lim, Joo Won; Lee, Ju Hie [Kyunghee Univ. Hospital, Seoul (Korea, Republic of)

    1996-06-01

    To analyse unusual radiologic manifestations of colonic adenocarcinoma, and to correlate these with pathologic findings. Radiologic findings of ten patients with atypical adenocarcinoma of the colon were retrospectively evaluated. The unusual radiologic findings were defined as terminal ileal involvement of the cecal mass, long segmental involvement of oner 9cm, and exophytic tumor growth. Radiologic and sonographic findings were compared with pathologic specimens obtained from surgical resection. Involvement of the terminal ileum was noted in three cases, long segmental involvement of 11 cm in five cases, and exophytic mass in two. of three cases with thickening of the terminal ileum, two revealed the infiltration of cancer into the terminal ileum through the ileocecal valve, and the other revealed vascular congesion and edema on microscopic examination. Five cases with long segmental involvement of over 11 cm comprised on e of cancer totally infiltrated through the submucosal and proper muscle layer, one of inflammatory thickening distal to the cancer, two of inflammatory change of pericolic fat and serosal adhesion and one of a large intraluminal fungating mass. In the cases of exophytic mass, one with a larger extraluminal and a smaller intraluminal component revealed necrosis and abscess on pathologic examination, accounting for low attenuation on CT, whereas the other, with exophytic growth, disclosed abundant pools of mucin, resulting in low attenuation on CT. These two cases could not be differentiated from submucosal tumors. Atypical colon cancer may have various manifestations, such as thickening of the terminal ileum, involvement of a long segment, and an exophytically growing mass. An appreciation of the radiologic findings of this cancer may therefore help in differential diagnosis in cases simulating colitis or submucosal tumors of the colon, such as lymphoma or leiomyoma.

  11. Adenocarcinoma of the Colon in a 10-year-old child | Siboe | Annals ...

    African Journals Online (AJOL)

    Colonic adenocarcinoma is rare in children, more so in the first decade of life. Owing to the non-specificity and vagueness of symptoms, most patients in this age group present with advanced malignacy. The authors report a case of adenocarcinoma of the colon in a 10-year-old female child presenting with a history of ...

  12. Potent in vivo anticancer activity and stability of liposomes encapsulated with semi-purified Job's tear (Coix lacryma-jobi Linn.) extracts on human colon adenocarcinoma (HT-29) xenografted mice.

    Science.gov (United States)

    Sainakham, Mathukorn; Manosroi, Aranya; Abe, Masahiko; Manosroi, Worapaka; Manosroi, Jiradej

    2016-11-01

    The in vivo anticancer activity and stability of liposomes encapsulated with semi-purified Job's tear (Coix lacryma-jobi Linn.) extracts (S5L), prepared by supercritical carbon dioxide fluid technique, on human colon adenocarcinoma (HT29) xenografted mice were investigated. For the stability and the physicochemical characteristics, S5L showed a high stability of pH, good dispersibility, small particle size and stable zeta potential. Liposomes can protect linoleic acid in the extract comparing with the free S5. S5L kept at 4 °C for 3 months showed the highest linoleic acid content of 63.50%, whereas at 45 °C, the lowest linoleic acid content of 42.66% was observed. The anticancer activity and toxicity on xenografted mice were observed for 14 days. At the end of the experiment, the relative tumor volume (RTV) in the S5L-treated xenografted mice showed a significant RTV reduction. The high dose of S5 and S5L were potent with the highest inhibition of tumor growth of 48.67 and 54.75%, which was 86.94% and 97.81% of 5-fluorouracil, respectively. The apoptotic activity was shown in xenografted mice treated with S5 at medium and high dose, S5L, 5-fluorouracil and commercial product. All treated xenografted mice showed no toxic signs and symptoms, abnormality of internal organs histopathology and blood chemistry. This study has demonstrated the high physicochemical stability of liposomes encapsulated with semi-purified Job's tear extract and their potent anticancer activity on human colon adenocarcinoma xenografted model with the potential for further development to anticolon cancer drug.

  13. Nuclear Matrix Proteins in Human Colon Cancer

    Science.gov (United States)

    Keesee, Susan K.; Meneghini, Marc D.; Szaro, Robert P.; Wu, Ying-Jye

    1994-03-01

    The nuclear matrix is the nonchromatin scaffolding of the nucleus. This structure confers nuclear shape, organizes chromatin, and appears to contain important regulatory proteins. Tissue specific nuclear matrix proteins have been found in the rat, mouse, and human. In this study we compared high-resolution two-dimensional gel electropherograms of nuclear matrix protein patterns found in human colon tumors with those from normal colon epithelia. Tumors were obtained from 18 patients undergoing partial colectomy for adenocarcinoma of the colon and compared with tissue from 10 normal colons. We have identified at least six proteins which were present in 18 of 18 colon tumors and 0 of 10 normal tissues, as well as four proteins present in 0 of 18 tumors and in 10 of 10 normal tissues. These data, which corroborate similar findings of cancer-specific nuclear matrix proteins in prostate and breast, suggest that nuclear matrix proteins may serve as important markers for at least some types of cancer.

  14. Synchronous Occurrence of Primary Breast Carcinoma and Primary Colon Adenocarcinoma.

    Science.gov (United States)

    Yetkin, Gurkan; Celayir, Fevzi; Akgun, Ismail Ethem; Ucak, Ramazan

    2017-01-01

    A 65-year-old female patient presented to the emergency clinic with abdominal pain, meteorism, and intermittent rectal bleeding. Colonoscopy was performed, and a hepatic flexure tumor was detected. Histopathological examination of biopsy revealed adenocarcinoma. Thoracoabdominal CT was performed for staging, and a spiculated contour mass was found incidentally on the left breast. Mammography and ultrasonography were performed for the cause of these findings, and suspicious lesions of malignancy were seen in the left breast. Invasive ductal carcinoma was detected in core needle biopsy samples from lesions. In the multidisciplinary council consisting of oncologist, pathologist, radiologist, and general surgery specialist, it was decided to perform breast operation first and then colon operation, followed by adjuvant chemotherapy. In the first operation, left total mastectomy and sentinel lymph node biopsy were performed. One week after her initial operation, the patient underwent right hemicolectomy. After operations, the patient did not develop postoperative complications and was sent to medical oncology department for adjuvant chemotherapy.

  15. A case of gastrocolic fistula secondary to adenocarcinoma of the colon

    Directory of Open Access Journals (Sweden)

    BiaoHuan Zhou

    2015-01-01

    Conclusion: It is rare for gastrocolic fistula case to be caused by colon adenocarcinoma, and has been rarely reported inside China. The best therapy of gastrocolic fistula remains radical en-bloc surgery.

  16. Synchronous Occurrence of Primary Breast Carcinoma and Primary Colon Adenocarcinoma

    Directory of Open Access Journals (Sweden)

    Gurkan Yetkin

    2017-01-01

    Full Text Available A 65-year-old female patient presented to the emergency clinic with abdominal pain, meteorism, and intermittent rectal bleeding. Colonoscopy was performed, and a hepatic flexure tumor was detected. Histopathological examination of biopsy revealed adenocarcinoma. Thoracoabdominal CT was performed for staging, and a spiculated contour mass was found incidentally on the left breast. Mammography and ultrasonography were performed for the cause of these findings, and suspicious lesions of malignancy were seen in the left breast. Invasive ductal carcinoma was detected in core needle biopsy samples from lesions. In the multidisciplinary council consisting of oncologist, pathologist, radiologist, and general surgery specialist, it was decided to perform breast operation first and then colon operation, followed by adjuvant chemotherapy. In the first operation, left total mastectomy and sentinel lymph node biopsy were performed. One week after her initial operation, the patient underwent right hemicolectomy. After operations, the patient did not develop postoperative complications and was sent to medical oncology department for adjuvant chemotherapy.

  17. Induction of Apoptosis and Cell Cycle Arrest by Flavokawain C on HT-29 Human Colon Adenocarcinoma via Enhancement of Reactive Oxygen Species Generation, Upregulation of p21, p27, and GADD153, and Inactivation of Inhibitor of Apoptosis Proteins.

    Science.gov (United States)

    Phang, Chung-Weng; Karsani, Saiful Anuar; Abd Malek, Sri Nurestri

    2017-07-01

    Chalcones have been shown to exhibit anti-cancer properties by targeting multiple molecular pathways. It was, therefore, of interest to investigate flavokawain C (FKC), a naturally occurring chalcone, which can be isolated from Kava (Piper methysticum Forst) root extract. The aim of this study was to investigate the inhibitory effect of FKC on the growth of HT-29 cells and its underlying mechanism of action. Cell viability of HT-29 cells was assessed by Sulforhodamine B assay after FKC treatment. Induction of apoptosis was examined by established morphological and biochemical assays. ROS generation was determined by dichlorofluorescein fluorescence staining, and superoxide dismutase activity was measured using the spectrophotometric method. Western blotting was used to examine the changes in the protein levels. FKC markedly decreased the cell viability of HT-29 cells and the cells showed dramatic changes in cellular and nuclear morphologies with typical apoptotic features. The induction of apoptosis correlated well with the externalization of phosphatidylserine, DNA fragmentation, decreased mitochondrial membrane potential, activation of caspases, and PARP cleavage. This was associated with an increase in reactive oxygen species and a decrease in SOD activity. The protein levels of XIAP, c-IAP1, and c-IAP2 were downregulated, whereas the GADD153 was upregulated after FKC treatment. FKC induced cell cycle arrest at the G1 and G2/M phases via upregulation of p21 and p27 in a p53-independent manner. Our results provide evidence that FKC has the potential to be developed into chemotherapeutic drug for the treatment of colon adenocarcinoma. Flavokawain C inhibited the growth of HT-29 human colon adenocarcinoma cellsFlavokawain C induced apoptosis in HT-29 cells, associated with an increase in reactive oxygen species and a decrease in SOD activityFlavokawain C induced cell cycle arrest at the G1 and G2/M phases via upregulation of p21 and p27 in HT-29 cellsHT-29 cells

  18. Sorbus rufopilosa Extract Exhibits Antioxidant and Anticancer Activities by Inducing Cell Cycle Arrest and Apoptosis in Human Colon Adenocarcinoma HT29 Cells

    Science.gov (United States)

    Oh, You Na; Jin, Soojung; Park, Hyun-Jin; Kwon, Hyun Ju; Kim, Byung Woo

    2016-01-01

    Background Sorbus rufopilosa, a tsema rowan, is a species of the small ornamental trees in the genus Sorbus and the family Rosaceae found in East Asia. The bioactivities of S. rufopilosa have not yet been fully determined. The objective of this study is to evaluate the antioxidant and anticancer effects of ethanol extract of S. rufopilosa (EESR) and to determine the molecular mechanism of its anticancer activity in human colon carcinoma HT29 cells. Methods To examine the antioxidant activity of EESR, 2,2-diphenyl-1-picrylhydrazyl radical scavenging activity assay was performed. Inhibitory effect of EESR on cancer cell growth and proliferation was determined by water-soluble tetrazolium salt assay. To investigate the mechanism of EESR-mediated cytotoxicity, HT29 cells were treated with various concentrations of EESR and the induction of cell cycle arrest and apoptosis was analyzed by flow cytometry, 4,6-diamidino-2-phenylindole staining, and Western blot analysis. Results EESR showed significant antioxidant activity and inhibitory effect on HT29 cell growth in a dose-dependent manner. EESR induced cell cycle arrest at G2/M phase in a dose-dependent manner by modulating cyclin B, cyclin-dependent kinase 1 (CDK1), and CDK inhibitor p21 expression. EESR-induced apoptosis was associated with the upregulation of p53, a death receptor Fas, and a pro-apoptotic protein Bax and the activation of caspase 3, 8, and 9, resulting in the degradation of PARP. Conclusions EESR possessing antioxidant activity efficiently inhibits proliferation of HT29 cells by inducing both cell cycle arrest and apoptosis. EESR may be a possible candidate for the anticancer drug development. PMID:28053959

  19. Distant Ureteral Metastasis from Colon Adenocarcinoma: Report of a Case and Review of the Literature

    Directory of Open Access Journals (Sweden)

    Ferakis Nikolaos

    2014-01-01

    Full Text Available Carcinomas arising from organs neighbouring the ureter can directly infiltrate the ureter. Distant ureteral metastasis from colon adenocarcinoma is extremely rare and usually an incidental finding in performed autopsies. We report a case of a right ureteral metastasis in a 65-year-old Caucasian male with a history of rectal cancer for which he had been treated 4 years before. He presented with asymptomatic moderate right hydronephrosis. The patient underwent a right nephroureterectomy. Histology of the ureter revealed transmural adenocarcinoma with infiltration of the mucosa. Infiltration of the muscular coat of the bladder was found 2 years later. Thus, cystectomy and left ureterocutaneostomy were performed. The patient died 6 months later due to toxic megacolon during chemotherapy. The differential diagnosis of ureteral adenocarcinoma, especially in patients with previous history of colon adenocarcinoma, should include the possibility of distant metastasis from the primary colonic tumor.

  20. Suppression of c-Myc is involved in multi-walled carbon nanotubes' down-regulation of ATP-binding cassette transporters in human colon adenocarcinoma cells

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Zhaojing [Department of Pharmacology, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, 430030 Wuhan (China); Xu, Yonghong [Institute of Ophthalmological Research, Department of Ophthalmology, Renmin Hospital of Wuhan University, 430060 Wuhan (China); Meng, Xiangning [School of Materials and Metallurgy, Northeastern University, Shenyang 110819 (China); Watari, Fumio [Department of Biomedical, Dental Materials and Engineering, Graduate School of Dental Medicine, Hokkaido University, Sapporo 060-8586 (Japan); Liu, Hudan, E-mail: hudanliu@hust.edu.cn [Department of Pharmacology, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, 430030 Wuhan (China); Chen, Xiao, E-mail: mornsmile@yahoo.com [Department of Pharmacology, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, 430030 Wuhan (China)

    2015-01-01

    Over-expression of ATP-binding cassette (ABC) transporters, a large family of integral membrane proteins that decrease cellular drug uptake and accumulation by active extrusion, is one of the major causes of cancer multi-drug resistance (MDR) that frequently leads to failure of chemotherapy. Carbon nanotubes (CNTs)-based drug delivery devices hold great promise in enhancing the efficacy of cancer chemotherapy. However, CNTs' effects on the ABC transporters remain under-investigated. In this study, we found that multiwalled carbon nanotubes (MWCNTs) reduced transport activity and expression of ABC transporters including ABCB1/Pgp and ABCC4/MRP4 in human colon adenocarcinoma Caco-2 cells. Proto-oncogene c-Myc, which directly regulates ABC gene expression, was concurrently decreased in MWCNT-treated cells and forced over-expression of c-Myc reversed MWCNTs' inhibitory effects on ABCB1 and ABCC4 expression. MWCNT-cell membrane interaction and cell membrane oxidative damage were observed. However, antioxidants such as vitamin C, β-mecaptoethanol and dimethylthiourea failed to antagonize MWCNTs' down-regulation of ABC transporters. These data suggest that MWCNTs may act on c-Myc, but not through oxidative stress, to down-regulate ABC transporter expression. Our findings thus shed light on CNTs' novel cellular effects that may be utilized to develop CNTs-based drug delivery devices to overcome ABC transporter-mediated cancer chemoresistance.

  1. Synchronous colonic adenocarcinoma and renal oncocytoma: a case report and literature review.

    Science.gov (United States)

    Dalli, J; Camilleri-Brennan, J

    2011-08-01

    We present the case of a patient with an adenocarcinoma of the colon associated with an oncocytoma of the kidney. A left colonic cancer was diagnosed at colonoscopy and an incidental finding of a left renal mass was noted, with a staging computerized tomography scan. Following a left hemicolectomy and a left nephrectomy, the pathological report confirmed the presence of a colonic adenocarcinoma and revealed that the left renal mass was an oncocytoma. This case report reviews the management decisions associated with incidental renal masses as well as the treatment of synchronous neoplasia.

  2. Papillary Adenocarcinoma of the descending colon in a dog: case report

    Directory of Open Access Journals (Sweden)

    M.G.P.A. Ferreira

    Full Text Available ABSTRACT The aim of this report was to describe the clinical findings and therapeutic management of a case of papillary adenocarcinoma of the descending colon in a Beagle. The patient presented soft stools, haematochezia, tenesmus, and dyschezia. Clinical examination revealed alterations on the ultrasonographic features of the descending colon suggestive of colitis and neoplasia. Following local mass resection, histopathology analysis revealed mild lymphoplasmocytic enteritis and papillary adenocarcinoma of the colon. Enterectomy for tumoral resection and biopsy of locoregional lymph nodes were carried out. Subsequent to the surgical procedure, it was possible to confirm the previous diagnosis and the tumor was classified as intestinal intraluminal papillary adenocarcinoma, with incomplete surgical margins. Adjuvant chemotherapy was performed using carboplatin, cyclophosphamide, and piroxicam, leading to remission of clinical signs and absence of any clinical or imaging alterations compatible with the patient’s previous clinical condition.

  3. Typing of colon and lung adenocarcinoma by high throughput imaging mass spectrometry.

    Science.gov (United States)

    Kriegsmann, Mark; Longuespée, Rémi; Wandernoth, Petra; Mohanu, Cristina; Lisenko, Katharina; Weichert, Wilko; Warth, Arne; Dienemann, Hendrik; De Pauw, Edwin; Katzenberger, Tiemo; Aust, Daniela; Baretton, Gustavo; Kriegsmann, Joerg; Casadonte, Rita

    2017-07-01

    In advanced tumor stages, diagnosis is frequently made from metastatic tumor tissue. In some cases, the identification of the tumor of origin may be difficult by histology alone. In this setting, immunohistochemical and molecular biological methods are often required. In a subset of tumors definite diagnosis cannot be achieved. Thus, additional new diagnostic methods are required for precise tumor subtyping. Mass spectrometric methods are of special interest for the discrimination of different tumor types. We investigated whether it is possible to discern adenocarcinomas of colon and lung using high-throughput imaging mass spectrometry on formalin-fixed paraffin-embedded tissue microarrays. 101 primary adenocarcinoma of the colon and 91 primary adenocarcinoma of the lung were used to train a Linear Discriminant Analysis model. Results were validated on an independent set of 116 colonic and 75 lung adenocarcinomas. In the validation cohort 109 of 116 patients with colonic and 67 of 75 patients with lung adenocarcinomas were correctly classified. The ability to define proteomic profiles capable to discern different tumor types promises a valuable tool in cancer diagnostics and might complement current approaches. This article is part of a Special Issue entitled: MALDI Imaging, edited by Dr. Corinna Henkel and Prof. Peter Hoffmann. Copyright © 2016 Elsevier B.V. All rights reserved.

  4. 1-(2,6-Dihydroxy-4-methoxyphenyl-2-(4-hydroxyphenyl Ethanone-Induced Cell Cycle Arrest in G1/G0 in HT-29 Cells Human Colon Adenocarcinoma Cells

    Directory of Open Access Journals (Sweden)

    Ma Ma Lay

    2014-01-01

    Full Text Available 1-(2,6-Dihydroxy-4-methoxyphenyl-2-(4-hydroxyphenyl ethanone (DMHE was isolated from the ethyl acetate fraction of Phaleria macrocarpa (Scheff. Boerl fruits and the structure confirmed by GC-MS (gas chromatography-mass spectrometry and NMR (nuclear magnetic resonance analysis. This compound was tested on the HT-29 human colon adenocarcinoma cell line using MTT (method of transcriptional and translational cell proliferation assay. The results of MTT assay showed that DMHE exhibited good cytotoxic effect on HT-29 cells in a dose- and time-dependent manner but no cytotoxic effect on the MRC-5 cell line after 72 h incubation. Morphological features of apoptotic cells upon treatment by DMHE, e.g., cell shrinkage and membrane blebbing, were examined by an inverted and phase microscope. Other features, such as chromatin condension and nuclear fragmentation were studied using acridine orange and propidium iodide staining under the fluorescence microscope. Future evidence of apoptosis/necrosis was provided by result fromannexin V-FITC/PI (fluorescein-isothiocyanate/propidium iodide staining revealed the percentage of early apoptotic, late apoptotic, necrotic and live cells in a dose- and time-dependent manner using flow cytometry. Cell cycle analysis showed G0/G1 arrest in a time-dependent manner. A western blot analysis indicated that cell death might be associated with the up-regulation of the pro-apoptotic proteins Bax PUMA. However, the anit-apotptic proteins Bcl-2, Bcl-xL, and Mcl-1 were also found to increase in a time-dependent manner. The expression of the pro-apoptotic protein Bak was not observed.

  5. Mertensene, a Halogenated Monoterpene, Induces G2/M Cell Cycle Arrest and Caspase Dependent Apoptosis of Human Colon Adenocarcinoma HT29 Cell Line through the Modulation of ERK-1/-2, AKT and NF-κB Signaling

    Directory of Open Access Journals (Sweden)

    Safa Tarhouni-Jabberi

    2017-07-01

    Full Text Available Conventional treatment of advanced colorectal cancer is associated with tumor resistance and toxicity towards normal tissues. Therefore, development of effective anticancer therapeutic alternatives is still urgently required. Nowadays, marine secondary metabolites have been extensively investigated due to the fact that they frequently exhibit anti-tumor properties. However, little attention has been given to terpenoids isolated from seaweeds. In this study, we isolated the halogenated monoterpene mertensene from the red alga Pterocladiella capillacea (S.G. Gmelin Santelices and Hommersand and we highlight its inhibitory effect on the viability of two human colorectal adenocarcinoma cell lines HT29 and LS174. Interestingly, exposure of HT29 cells to different concentrations of mertensene correlated with the activation of MAPK ERK-1/-2, Akt and NF-κB pathways. Moreover, mertensene-induced G2/M cell cycle arrest was associated with a decrease in the phosphorylated forms of the anti-tumor transcription factor p53, retinoblastoma protein (Rb, cdc2 and chkp2. Indeed, a reduction of the cellular level of cyclin-dependent kinases CDK2 and CDK4 was observed in mertensene-treated cells. We also demonstrated that mertensene triggers a caspase-dependent apoptosis in HT29 cancer cells characterized by the activation of caspase-3 and the cleavage of poly (ADP-ribose polymerase (PARP. Besides, the level of death receptor-associated protein TRADD increased significantly in a concentration-dependent manner. Taken together, these results demonstrate the potential of mertensene as a drug candidate for the treatment of colon cancer.

  6. Diagnosis potential of near infrared Mueller Matrix imaging for colonic adenocarcinoma

    Science.gov (United States)

    Wang, Jianfeng; Zheng, Wei; Lin, Kan; Huang, Zhiwei

    2016-03-01

    Mueller matrix imaging along with polar decomposition method was employed for the colonic adenocarcinoma detection by polarized light in the near-infrared spectral range (700-1100 nm). A high-speed (5s) Muller matrix imaging system with dual-rotating waveplates was developed. 16 (4 by 4) full Mueller matrices of the colonic tissues (i.e., normal and caner) were acquired. Polar decomposition was further implemented on the 16 images to derive the diattentuation, depolarization, and the retardance images. The decomposed images showed clear margin between the normal and adenocarcinomaous colon tissue samples. The work shows the potential of near-infrared Mueller matrix imaging for the early diagnosis and detection of malignant lesions in the colon.

  7. Carcino-embryonic antigen in monitoring the growth of human colon adenocarcinoma tumour cells SK-CO-1 and HT-29 in vitro and in nude mice

    DEFF Research Database (Denmark)

    Sölétormos, G; Fogh, J M; Sehested-Hansen, B

    1997-01-01

    A set of experimental model systems were designed to investigate (a) the inter-relationship between growth of two human cancer cell lines (SK-CO-1, HT-29) and carcino-embryonic antigen (CEA) kinetics; and (b) whether neoplastic growth or CEA concentration is modulated by human growth hormone (h....... In conclusion, our results suggest that experimental models may be useful for investigating the role of serological markers as monitors of increasing tumour burden. It will be of interest to investigate the performance of those model systems in examining the effect of cytotoxic agents in neoplastic growth....

  8. Papillary Adenocarcinoma of the descending colon in a dog: case report

    OpenAIRE

    Ferreira, M.G.P.A.; Ribeiro, J.O.; Pascoli, A.L.; Reis-Filho, N.P.; Beluque, T.; Santos, M.Q.P.; Theodoro, S.S.; Feliciano, M.A.R.; Nardi, A.B.; Tinucci-Costa, M.; Moraes, P.C.; Canola, J.C.; Carciofi, A.C.

    2017-01-01

    ABSTRACT The aim of this report was to describe the clinical findings and therapeutic management of a case of papillary adenocarcinoma of the descending colon in a Beagle. The patient presented soft stools, haematochezia, tenesmus, and dyschezia. Clinical examination revealed alterations on the ultrasonographic features of the descending colon suggestive of colitis and neoplasia. Following local mass resection, histopathology analysis revealed mild lymphoplasmocytic enteritis and papillary ad...

  9. Metastasis to the appendix from adenocarcinoma of the ascending colon: A case report.

    Science.gov (United States)

    Li, Yingjie; Li, Mingshan; Li, Xiaoxia; Sang, Haiquan

    2017-03-01

    Metastasis of cancer cells involves shedding from the primary tumor through various means to distant tissues and organs with continued growth and formation of new metastatic tumors of the same cancer type as the original tumor. The common sites for colon cancer metastases include the pelvis, retroperitoneal lymph nodes, liver, and lungs; Colon cancer metastases to the appendix are rare, as reported in this case. A 45-year-old man was admitted to our department with a 24-hour history of abdominal distension and incomplete obstruction. Colonoscopy showed an elevated lesion in the ascending colon and the pathologic diagnosis was adenocarcinoma. This patient underwent a radical right hemi-colectomy. The post-operative pathologic examination revealed metastatic adenocarcinoma in all layers of the appendix, especially the muscularis mucosae. The diagnosis was adenocarcinoma of the ascending colon (pT4bN2bM0 stage IIIC) with metastatic adenocarcinoma of the appendix. An absent right colic artery with lymph node fusion might increase the risk of appendiceal cancer metastasis.

  10. Synchronous Occurrence of Primary Breast Carcinoma and Primary Colon Adenocarcinoma

    OpenAIRE

    Gurkan Yetkin; Fevzi Celayir; Ismail Ethem Akgun; Ramazan Ucak

    2017-01-01

    A 65-year-old female patient presented to the emergency clinic with abdominal pain, meteorism, and intermittent rectal bleeding. Colonoscopy was performed, and a hepatic flexure tumor was detected. Histopathological examination of biopsy revealed adenocarcinoma. Thoracoabdominal CT was performed for staging, and a spiculated contour mass was found incidentally on the left breast. Mammography and ultrasonography were performed for the cause of these findings, and suspicious lesions of malignan...

  11. Colon cancer

    Science.gov (United States)

    Colorectal cancer; Cancer - colon; Rectal cancer; Cancer - rectum; Adenocarcinoma - colon; Colon - adenocarcinoma; Colon carcinoma ... eat may play a role in getting colon cancer. Colon cancer may be linked to a high-fat, ...

  12. Clear Cell Adenocarcinoma of the Colon: A Case Report and Review of the Literature

    Directory of Open Access Journals (Sweden)

    Christian Daniel Barrera-Maldonado

    2014-01-01

    Full Text Available Clear cell adenocarcinoma of the colon has been described scarcely in the literature. It affects elderly men more commonly than women and usually appears in the left side of the colon. A Hispanic 41-year-old female came to the emergency room with abdominal pain, vomiting, and distension. Physical exam revealed generalized tenderness without peritoneal signs. Laboratory data was unremarkable. A CT scan showed an apple-core lesion in the distal colon. A flexible sigmoidoscopy revealed an obstructive mass that made further evaluation impossible. Exploratory surgery revealed a hard mass obstructing the descending colon, which was resected. Histopathology analysis with immunohistochemistry staining was positive for cytokeratin 20, cytokeratin 10, CDX2, and villin, while it was negative for cytokeratin 7, RCC, vimentin, and CD31. These results confirmed the clear cell variant of the adenocarcinoma. Clear cell adenocarcinomas usually arise from the kidneys and Müllerian organs. Immunohistochemistry is crucial for establishing the origin of these neoplastic cells. A cytokeratin 20+/7− with positive CDX2 is highly specific and sensitive for intestinal neoplastic origin. The main treatment has been surgery alone with moderately good results. More research and information about this malignancy is needed, especially in regard to prognosis and in order to provide the best treatment option.

  13. Explant cultures of human colon

    DEFF Research Database (Denmark)

    Autrup, Herman; Barrett, L.A.; Jackson, F.E.

    1978-01-01

    . The ability to maintain colonic mucosa in culture was subject to both intra- and interindividual variation. Cultured human colonic mucosa also activated a chemical procarcinogen, benzo[a]pyrene, into metabolites which bound to cellular DNA. A 100-fold interindividual variation in this binding was observed.......Human colonic epithelium has been cultured as explants in a chemically defined medium for periods of 1 to 20 days. The viability of the explants was shown by the preservation of the ultrastructural features of the colonic epithelial cells and by active incorporation of radioactive precursors...... into cellular DNA and protein. A progressive decrease in the number of goblet cells, decrease in the depth of the crypts, and a change from a columnar to a cuboidal epithelium were observed. After 20 days in culture the colonic mucosa consisted of a single layer of cuboidal epithelial cells and a few glands...

  14. Unusual metachronous isolated inguinal lymph node metastasis from adenocarcinoma of the sigmoid colon

    Directory of Open Access Journals (Sweden)

    Parodo Giuseppina

    2011-10-01

    Full Text Available Abstract This study aimed to describe an unusual case of metachronous isolated inguinal lymph nodes metastasis from sigmoid carcinoma. A 62-year-old man was referred to our department because of an obstructing sigmoid carcinoma. Colonoscopy showed the obstructing lesion at 30 cm from the anal verge and abdominal CT revealed a sigmoid lesion infiltrating the left lateral abdominal wall. The patient underwent a colonic resection extended to the abdominal wall. Histology showed an adenocarcinoma of the colon infiltrating the abdominal wall with iuxtacolic nodal involvement. Thirty three months after surgery abdominal CT and PET scan revealed a metastatic left inguinal lymph node involvement. The metastatic lymph node was found strictly adherent to the left iliac-femoral artery and encompassing the origin of the left inferior epigastric artery. Histology showed a metachronous nodal metastasis from colonic adenocarcinoma. Despite metastastic involvement of inguinal lymph node from rectal cancer is a rare but well known clinical entity, to the best of our knowledge, this is the first report of inguinal metastasis from a carcinoma of the left colon. Literature review shows only three other similar reported cases: two cases of inguinal metastasis secondary to adenocarcinoma of the cecum and one case of axillary metastasis from left colonic carcinoma. A metastatic pathway through superficial abdominal wall lymphatic vessels could be possible through the route along the left inferior epigastric artery. The solitary inguinal nodal involvement from rectal carcinoma could have a more favorable prognosis. In the case of nodal metastasis to the body surface lymph nodes from colonic carcinoma, following the small number of such cases reported in the literature, no definitive conclusions can be drawn.

  15. Metastatic Colonic Adenocarcinoma in Breast: Report of Two Cases and Review of the Literature

    Directory of Open Access Journals (Sweden)

    Jiten P. Kothadia

    2015-01-01

    Full Text Available Metastatic adenocarcinoma to the breast from an extramammary site is extremely rare. In the literature, the most current estimate is that extramammary metastases account for only 0.43% of all breast malignancies and that, of these extramammary sites, colon cancer metastases form a very small subset. Most commonly seen metastasis in breast is from a contralateral breast carcinoma, followed by metastasis from hematopoietic neoplasms, malignant melanoma, sarcoma, lung, prostate, and ovary and gastric neoplasms. Here we present two rare cases, in which colonic adenocarcinomas were found to metastasize to the breast. In both cases, core biopsies were obtained from the suspicious areas identified on mammogram. Histopathology revealed neoplastic proliferation of atypical glandular components within benign breast parenchyma which were morphologically consistent with metastatic adenocarcinoma. By immunohistochemical staining, it was confirmed that the neoplastic components were immunoreactive to colonic markers and nonreactive to breast markers, thus further supporting the morphologic findings. It is extremely important to make this distinction between primary breast cancer and a metastatic process, in order to provide the most effective and appropriate treatment for the patient and to avoid any harmful or unnecessary surgical procedures.

  16. Rutamarin, an Active Constituent from Ruta angustifolia Pers., Induced Apoptotic Cell Death in the HT29 Colon Adenocarcinoma Cell Line.

    Science.gov (United States)

    Suhaimi, Shafinah Ahmad; Hong, Sok Lai; Abdul Malek, Sri Nurestri

    2017-07-01

    : ACN: Acetonitrile, ANOVA: One-way analysis of variance, BrdU: Bromodeoxyuridine, 13C-NMR: Carbon-13 Nuclear magnetic resonance, CAD: Caspase-activated endonuclease, CCD-18Co: Human colon normal, DLD1: Human Duke's type C colorectal adenocarcinoma, DMRT: Duncan's multiple range test, DMSO: Dimethyl sulfoxide, DNA: Deoxyribonucleic acid, DR4/5: Death receptor 4/5 protein, EMEM: Eagle's minimum essential media, FBS: Fetal bovine serum, FITC Annexin V: Annexin V conjugated with fluorescein isothiocyanate, FITC-DEVD-FMK: Fluorescein isothiocyanate conjugate of caspase inhibitor Asp-Glu-Val-Asp-fluoromethyl ketone, FITC-IETD-FMK: Fluorescein isothiocyanate conjugate of caspase inhibitor Ile-Glu-Thr-Asp-fluoromethyl ketone, FITC-LEHD-FMK: Fluorescein isothiocyanate conjugate of caspase inhibitor Leu-Glu-His-Asp-fluoromethyl ketone, G0: Quiescent phase of cell cycle, G1: Gap 1 phase of cell cycle, G2: Gap 2 phase of cell cycle, GC-MS: Gas chromatography-mass spectrometry, HeLa: Human cervical adenocarcinoma, HPLC: High performance liquid chromatography, HT29: Human colon adenocarcinoma, Huh7.5: Human hepatocellular carcinoma, IC50: Half maximal inhibitory concentration, KSHV: Kaposi's sarcoma-associated herpesvirus, M phase: Mitotic phase of cell cycle, MCF7: Human breast adenocarcinoma, NMR: Nuclear magnetic resonance, PBS: Phosphate-buffered saline, PI: Propidium iodide, RNase: Ribonuclease, rt: Retention time, S phase: Synthesis phase of cell cycle, SD: Standard deviation, SRB: Sulforhodamine B, TCA: Trichloroacetic acid, TLC: Thin layer chromatography, TNF-R1: Tumor necrosis factor receptor 1 protein, TUNEL: Terminal deoxynucleotidyl transferase (TdT) dUTP nick-end labeling, UV: Ultraviolet.

  17. Follistatin is a novel biomarker for lung adenocarcinoma in humans.

    Directory of Open Access Journals (Sweden)

    Fangfang Chen

    Full Text Available Follistatin (FST, a single chain glycoprotein, is originally isolated from follicular fluid of ovary. Previous studies have revealed that serum FST served as a biomarker for pregnancy and ovarian mucinous tumor. However, whether FST can serve as a biomarker for diagnosis in lung adenocarcinoma of humans remains unclear.The study population consisted of 80 patients with lung adenocarcinoma, 40 patients with ovarian adenocarcinoma and 80 healthy subjects. Serum FST levels in patients and healthy subjects were measured using ELISA. The results showed that the positive ratio of serum FST levels was 51.3% (41/80, which was comparable to the sensitivity of FST in 40 patients with ovarian adenocarcinoma (60%, 24/40 using the 95th confidence interval for the healthy subject group as the cut-off value. FST expressions in lung adenocarcinoma were examined by immunohistochemical staining, we found that lung adenocarcinoma could produce FST and there was positive correlation between the level of FST expression and the differential degree of lung adenocarcinoma. Furthermore, the results showed that primary cultured lung adenocarcinoma cells could secrete FST, while cells derived from non-tumor lung tissues almost did not produce FST. In addition, the results of CCK8 assay and flow cytometry showed that using anti-FST monoclonal antibody to neutralize endogenous FST significantly augmented activin A-induced lung adenocarcinoma cells apoptosis.These data indicate that lung adenocarcinoma cells can secret FST into serum, which may be beneficial to the survival of adenocarcinoma cells by neutralizing activin A action. Thus, FST can serve as a promising biomarker for diagnosis of lung adenocarcinoma and a useful biotherapy target for lung adenocarcinoma.

  18. Follistatin Is a Novel Biomarker for Lung Adenocarcinoma in Humans

    Science.gov (United States)

    Feng, Ye; Liu, Haiyan; Sun, Yang; Liu, Zhonghui; Ge, Jingyan; Cui, Xueling

    2014-01-01

    Background Follistatin (FST), a single chain glycoprotein, is originally isolated from follicular fluid of ovary. Previous studies have revealed that serum FST served as a biomarker for pregnancy and ovarian mucinous tumor. However, whether FST can serve as a biomarker for diagnosis in lung adenocarcinoma of humans remains unclear. Methods and Results The study population consisted of 80 patients with lung adenocarcinoma, 40 patients with ovarian adenocarcinoma and 80 healthy subjects. Serum FST levels in patients and healthy subjects were measured using ELISA. The results showed that the positive ratio of serum FST levels was 51.3% (41/80), which was comparable to the sensitivity of FST in 40 patients with ovarian adenocarcinoma (60%, 24/40) using the 95th confidence interval for the healthy subject group as the cut-off value. FST expressions in lung adenocarcinoma were examined by immunohistochemical staining, we found that lung adenocarcinoma could produce FST and there was positive correlation between the level of FST expression and the differential degree of lung adenocarcinoma. Furthermore, the results showed that primary cultured lung adenocarcinoma cells could secrete FST, while cells derived from non-tumor lung tissues almost did not produce FST. In addition, the results of CCK8 assay and flow cytometry showed that using anti-FST monoclonal antibody to neutralize endogenous FST significantly augmented activin A-induced lung adenocarcinoma cells apoptosis. Conclusions These data indicate that lung adenocarcinoma cells can secret FST into serum, which may be beneficial to the survival of adenocarcinoma cells by neutralizing activin A action. Thus, FST can serve as a promising biomarker for diagnosis of lung adenocarcinoma and a useful biotherapy target for lung adenocarcinoma. PMID:25347573

  19. 15-Hydroxyprostaglandin dehydrogenase as a marker in colon carcinogenesis: analysis of the prostaglandin pathway in human colonic tissue

    Directory of Open Access Journals (Sweden)

    Dong-Hoon Yang

    2017-01-01

    Full Text Available Background/Aims: Cyclooxygenase-2 (COX-2, 15-hydroxyprostaglandin dehydrogenase (15-PGDH, and microsomal prostaglandin E synthase-1 (mPGEs-1 regulate prostaglandin E₂ (PGE₂ expression and are involved in colon carcinogenesis. We investigated the expression of PGE₂ and its regulating genes in sporadic human colon tumors and matched normal tissues.Methods: Twenty colonic adenomas and 27 colonic adenocarcinomas were evaluated. COX-2 and 15-PGDH expression was quantified by real-time polymerase chain reaction. The expression of PGE₂ and mPGEs-1 was measured using enzyme-linked immunosorbent assay and Western blotting, respectively.Results: The expression of COX-2, mPGEs-1, and PGE₂ did not differ between the adenomas and matched distant normal tissues. 15-PGDH expression was lower in adenomas than in the matched normal colonic tissues (P<0.001. In adenocarcinomas, mPGEs-1 and PGE₂ expression was significantly higher (P<0.001 and P=0.020, respectively, and COX-2 expression did not differ from that in normal tissues (P=0.207. 15-PGDH expression was significantly lower in the normal colonic mucosa from adenocarcinoma patients than in the normal mucosa from adenoma patients (P=0.018.Conclusions: Early inactivation of 15-PGDH, followed by activation of COX-2 and mPGEs-1, contributes to PGE₂ production, leading to colon carcinogenesis. 15-PGDH might be a novel candidate marker for early detection of field defects in colon carcinogenesis.

  20. Combination of atorvastatin with sulindac or naproxen profoundly inhibits colonic adenocarcinomas by suppressing the p65/β-catenin/cyclin D1 signaling pathway in rats.

    Science.gov (United States)

    Suh, Nanjoo; Reddy, Bandaru S; DeCastro, Andrew; Paul, Shiby; Lee, Hong Jin; Smolarek, Amanda K; So, Jae Young; Simi, Barbara; Wang, Chung Xiou; Janakiram, Naveena B; Steele, Vernon; Rao, Chinthalapally V

    2011-11-01

    Evidence supports the protective role of nonsteroidal anti-inflammatory drugs (NSAID) and statins against colon cancer. Experiments were designed to evaluate the efficacies atorvastatin and NSAIDs administered individually and in combination against colon tumor formation. F344 rats were fed AIN-76A diet, and colon tumors were induced with azoxymethane. One week after the second azoxymethane treatment, groups of rats were fed diets containing atorvastatin (200 ppm), sulindac (100 ppm), naproxen (150 ppm), or their combinations with low-dose atorvastatin (100 ppm) for 45 weeks. Administration of atorvastatin at 200 ppm significantly suppressed both adenocarcinoma incidence (52% reduction, P = 0.005) and multiplicity (58% reduction, P = 0.008). Most importantly, colon tumor multiplicities were profoundly decreased (80%-85% reduction, P < 0.0001) when given low-dose atorvastatin with either sulindac or naproxen. Also, a significant inhibition of colon tumor incidence was observed when given a low-dose atorvastatin with either sulindac (P = 0.001) or naproxen (P = 0.0005). Proliferation markers, proliferating cell nuclear antigen, cyclin D1, and β-catenin in tumors of rats exposed to sulindac, naproxen, atorvastatin, and/or combinations showed a significant suppression. Importantly, colon adenocarcinomas from atorvastatin and NSAIDs fed animals showed reduced key inflammatory markers, inducible nitric oxide synthase and COX-2, phospho-p65, as well as inflammatory cytokines, TNF-α, interleukin (IL)-1β, and IL-4. Overall, this is the first report on the combination treatment using low-dose atorvastatin with either low-dose sulindac or naproxen, which greatly suppress the colon adenocarcinoma incidence and multiplicity. Our results suggest that low-dose atorvastatin with sulindac or naproxen might potentially be useful combinations for colon cancer prevention in humans.

  1. Lynch Syndrome Associated Colon Adenocarcinoma Resembling Lymphoma on Fluoro-Deoxyglucose-Positron Emission Tomography/Computed Tomography.

    Science.gov (United States)

    Aparici, Carina Mari; Win, Aung Zaw

    2015-01-01

    The patient was a 46-year-old Asian male diagnosed with lynch syndrome associated colon adenocarcinoma in the right ascending colon. A presurgical staging 18-fluoro-deoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) found increased metabolic activity in the cervical, axillary, mediastinal, supraclavicular, para-aortic and mesenteric lymph nodes. This pattern of metastasis was very unusual for lynch syndrome associated colon adenocarcinoma and the involvement of those lymph nodes resembles the pattern of spread of lymphoma. He underwent right hemicolectomy and he was subsequently treated with 12 cycles of folinic acid (leucovorin), fluorouracil (5-FU), irinotecan. A restaging FDG-PET/CT at the end of the chemotherapy showed interval decrease in size and metabolic activity in the affected lymph nodes. FDG-PET/CT is a useful imaging modality in following-up the treatment response in colon adenocarcinoma.

  2. A review of 18 cases of feline colonic adenocarcinoma treated with subtotal colectomies and adjuvant carboplatin.

    Science.gov (United States)

    Arteaga, Theresa A; McKnight, JoAnne; Bergman, Philip J

    2012-01-01

    Feline colonic adenocarcinoma is a locally invasive, highly metastatic tumor that is most often treated with wide surgical excision (subtotal colectomy) and systemic chemotherapy either with or without nonsteroidal anti-inflammatory medications. In this retrospective study, the outcome of subtotal colectomy and adjuvant carboplatin in 18 client-owned cats is described. The median carboplatin dose was 200 mg/m(2) (range, 200-254 mg/m(2)) q 4 wk with a median of five doses/cat (range was two to seven doses/cat). Limited toxicities were noted. Positive prognostic factors for the disease-free interval included cats that had weight loss as a presenting sign (P adenocarcinoma.

  3. Induction of apoptosis in human breast adenocarcinoma MCF-7 ...

    African Journals Online (AJOL)

    Induction of apoptosis in human breast adenocarcinoma MCF-7 cells by tannic acid and resveratrol. Ahu Soyocak, Didem Turgut Cosan, Ayse Basaran, Hasan Veysi Gunes, Irfan Degirmenci, Fezan Sahin Mutlu ...

  4. Decorin in Human Colon Cancer

    Science.gov (United States)

    Nyman, Marie C.; Sainio, Annele O.; Pennanen, Mirka M.; Lund, Riikka J.; Vuorikoski, Sanna; Sundström, Jari T. T.

    2015-01-01

    Decorin is generally recognized as a tumor suppressing molecule. Nevertheless, although decorin has been shown to be differentially expressed in malignant tissues, it has often remained unclear whether, in addition to non-malignant stromal cells, cancer cells also express it. Here, we first used two publicly available databases to analyze the current information about decorin expression and immunoreactivity in normal and malignant human colorectal tissue samples. The analyses demonstrated that decorin expression and immunoreactivity may vary in cancer cells of human colorectal tissues. Therefore, we next examined decorin expression in normal, premalignant and malignant human colorectal tissues in more detail using both in situ hybridization and immunohistochemistry for decorin. Our results invariably demonstrate that malignant cells within human colorectal cancer tissues are devoid of both decorin mRNA and immunoreactivity. Identical results were obtained for cells of neuroendocrine tumors of human colon. Using RT-qPCR, we showed that human colon cancer cell lines are also decorin negative, in accordance with the above in vivo results. Finally, we demonstrate that decorin transduction of human colon cancer cell lines causes a significant reduction in their colony forming capability. Thus, strategies to develop decorin-based adjuvant therapies for human colorectal malignancies are highly rational. PMID:26001829

  5. Perforated mixed carcinoid-adenocarcinoma in transverse colon and at gastroenterostomy site: case report

    Directory of Open Access Journals (Sweden)

    Karakaş Barış R

    2010-12-01

    Full Text Available Abstract Goblet cell carcinoid of the large intestine is a rare neoplasm, usually located in ascending colon and rectum. A 60-year-old male patient underwent surgery after the diagnosis of acute abdomen. Exploratory laparotomy revealed perforation with a diameter of 1 cm at the site of the previously performed gastroenterostomy and dilatation of the right colic flexure, secondary to a solid obstructive mass located in the mid-portion of transverse colon. Histopathological investigation of the biopsies, taken from the gastroenterostomy site and the tumor, revealed mixed carcinoid-adenocarcinoma with carcinoid component, predominantly composed of goblet cells. Three cycles of FOLFOX-4 protocol was administered. Following respiratory distress secondary to pulmonary metastasis, the patient's condition deteriorated and subsequently died in the fourth postoperative month. Our aim with this paper is to point out that more cases should be reported for more effective diagnosis, histopathological study, clinical investigation, treatment and prognosis of this specific neoplasm.

  6. A case-report of synchronous adenocarcinoma and gastrointestinal stromal tumor of the colon

    Directory of Open Access Journals (Sweden)

    A. O. Rasulov

    2015-01-01

    Full Text Available Synchronous colonic tumors of different morphology are rarely described in the literature and do not have a clear ethiological connection. This fact is the key to a more detailed study of the clinical and morphological and molecular genetic features of different gistotipov synchronous tumors. There is increasing publications and clinical observations of simultaneous coexistence of adenocarcinoma and gastrointestinal stromal tumor. A separate and very valuable space is given interaction surgeons oncologists and pathologists. Today, for the correct pathological diagnosis of synchronous tumors of different biological nature, it is obligatory to conduct immunohistochemical study. Data on the results of treatment of synchronous tumors must necessarily be recorded in the cancer registries. Based on that, the developed algorithms timely diagnosis and proper treatment strategy in the cohort of patients. We present a case report of a 56 year old patient with a rare synchronous epithelial and non-epithelial colon tumors. 

  7. Screening key genes and miRNAs in early-stage colon adenocarcinoma by RNA-sequencing.

    Science.gov (United States)

    Liu, Jixi; Liu, Fang; Li, Xiaoou; Song, Xin; Zhou, Lei; Jie, Jianzheng

    2017-07-01

    Colon adenocarcinoma is the third leading cause of cancer-related deaths across the world, developing novel and non-invasive diagnostic and prognostic biomarkers for the early-stage colon adenocarcinoma at molecular level is essential. In our study, RNA-sequencing was performed to identify the differentially expressed genes and miRNAs (DEmiRNAs) in early-stage colon adenocarcinoma compared to tissues of precancerous lesions, colonic intraepithelial neoplasia. The DEmiRNA-target interaction network was constructed and functional annotation of targets of DEmiRNAs was performed. The Cancer Genome Atlas was used to verify the expression of selected differentially expressed genes. The receiver operating characteristic analyses of selected differentially expressed genes was performed. In total, 865 differentially expressed genes, 26 DEmiRNAs, and 329 DEmiRNA-target pairs were obtained. Based on the early-stage colon adenocarcinoma network, miR-548c-5p, miR-548i, and miR-548am-5p were the top three DEmiRNAs that covered most differentially expressed genes. NTRK2, DTNA, and BTG2 were the top three differentially expressed genes regulated by most DEmiRNAs. Cancer and colorectal cancer pathways were two significantly enriched pathways in early-stage colon adenocarcinoma. The common differentially expressed genes in both the pathways were AXIN2, Smad2, Smad4, PIK3R1, and BCL2. The expression levels of eight differentially expressed genes (NTRK2, DTNA, BTG2, COL11A1, Smad2, Smad4, PIK3R1, and BCL2) in The Cancer Genome Atlas database were compatible with our RNA-sequencing. All these eight differentially expressed genes and AXIN2 had the potential diagnosis value for Colon adenocarcinoma. In conclusion, a total of ten differentially expressed genes (NTRK2, DTNA, BTG2, COLCA1, COL11A1, AXIN2, Smad2, Smad4, PIK3R1, and BCL2) and four DEmiRNAs (miR-548c-5p, miR-548i, mir-424-5p, and miR-548am-5p) may be involved in the pathogenesis of early-stage colon adenocarcinoma which may

  8. Ileocecal-colonic intussusception caused by cecal adenocarcinoma A case report.

    Science.gov (United States)

    Verre, Luigi; Rossi, Rachele; Gaggelli, Ilaria; Piccolomini, Alessandro; Podzemny, Vlasta; Tirone, Andrea

    2012-09-12

    INTRODUCTION: Intussusception in adults is an infrequent cause of intestinal occlusion that is usually due to neoplasm lesions. The unspecific nature of the clinical presentation often delays diagnosis. It is most commonly emergency explorative laparotomy which clarifies the etiology of the occlusion. The authors report a case of intestinal occlusion caused by ileocecal-colonic invagination with a small cecal adenocarcinoma as lead point, in a 74-year-old woman. CASE REPORT: A 74-year-old woman came to the Emergency Department, complaining of crampy pain in the mid- and lower abdomen. An abdominal ultrasound revealed a "pseudokidney sign" apparently involving the cecum. Because there were no clear signs of occlusion, the patient was dicharged on the same day. Three days later, upon admission, the patient complained of episodes of abdominal pain with intervals of moderate well-being, associated with nausea, vomiting and an inability to pass stool (but not gas) for 36 hours. On clinical examination her abdomen was distended and tender on palpation in all quadrants, especially in the right iliac fossa where a large mass could be felt. Standard abdominal x-Ray documented gaseous distension of some loops of the jejunum-ileum with some air-fluid level. The patient underwent an abdominal CT scan which showed advanced intussusception that appeared to be ileocolic and multiple enlarged lymphnodes were found in the invaginated mesentery at the base of which there appears to be a thickening of the intestinal wall that is probably neoplastic in nature. The patient underwent explorative laparotomy. Ileocecal-colonic intussusception caused by a cecal growth 5 cm in diameter was found on examination of the surgical specimen. Histology showed that the cause of the large swelling of the ascending colon was a vegetating ulcerated adenocarcinoma (medium grade differentiation: G2), measuring 6.5x 4.0 cm, arising from a tubulovillous adenoma infiltrating the submucosa. CONCLUSIONS

  9. [Acute "pseudo-angiocholitis" due to colonic adenocarcinoma in a man with primary sclerosis cholangitis and ulcerative colitis].

    Science.gov (United States)

    Coatmeur, Olivier; Rassiat, Emmanuel; Bonniaud, Pierre; Jouve, Jean-Louis; Minello, Anne; Bedenne, Laurent; Faivre, Jean; Hillon, Patrick

    2003-12-01

    We report the case of a 49-Year-old-man with primary sclerosis cholangitis (PSC) and ulcerative colitis who developed two acute episodes of pseudo-angiocholitis. Both episodes were triggered by septic hepatitis translocated from ulcerative colonic adenocarcinoma. The biliary MRI did not show any signs of lithiasis or cholangiocarcinoma. cholangiocarcinoma, intra-hepatic lithiasis and colonic cancer are potential diagnoses in patients with PSC who develop angiocholitis.

  10. Spheroid-type of AL amyloid deposition associated with colonic adenocarcinoma: A case report with literature review.

    Science.gov (United States)

    Kim, Moon Joo; McCroskey, Zulfia; Piao, Yingchao; Belcheva, Anna; Truong, Luan; Kurtin, Paul J; Ro, Jae Y

    2017-12-08

    We report a colonic adenocarcinoma associated with diffuse submucosal deposition of a peculiar spheroid-type amyloid identified in the colon, terminal ileum, and appendix. A 65-year-old woman with past medical histories of hypertension, and chronic obstructive pulmonary disease, presented to the emergency room with cramping abdominal pain and nausea. A computed tomography (CT) scan of abdomen showed right colonic volvulus. Emergency right hemicolectomy was performed. The specimen showed colonic adenocarcinoma with focal submucosal invasion (pT1) arising from a villotubular adenoma. A diffuse submucosal spheroid-type amyloid deposition (resembling corpora amylacea-like structures with Liesegang ring formation) was identified in the colon, ileum, and appendix. Electron microscopy examination of this unusual spheroidal-type material further confirmed the presence of amyloid fibrils. Analysis by liquid chromatography-mass spectrometry detected AL (lambda) type amyloidosis in this specimen. Tests for monoclonal gammopathy were not performed because patient consent was not obtained. In tissue section evaluation, however, no plasma cell neoplasm was identified. Cases with isolated AL amyloid deposition in the gastrointestinal tract have been reported rarely, and there is no case report of colonic adenocarcinoma associated with primary amyloid deposition in the English literature. © 2017 Japanese Society of Pathology and John Wiley & Sons Australia, Ltd.

  11. Differences in protein expression and gene amplification of cyclins between colon and rectal adenocarcinomas.

    Science.gov (United States)

    Aamodt, Rolf; Jonsdottir, Kristin; Andersen, Solveig Norheim; Bondi, Johan; Bukholm, Geir; Bukholm, Ida R K

    2009-01-01

    Adenocarcinomas of rectum and colon may be different with regard to the cellular biological basis for cancer development. A material of 246 rectal cancers removed surgically at Akershus University Hospital in the years 1992-2000 was investigated and was compared to a material of 219 colon cancers operated on at Akershus University Hospital during the years 1988, 1990 and 1997-2000. There were highly significant differences between the rectal and the colon cancers in the protein expression of cyclin D1, cyclin D3, cyclin E, nuclear beta-catenin, and c-Myc and in gene amplification of cyclin A2, cyclin B1, cyclin D1, and cyclin E. Gene amplification and protein expression in the rectal cancers correlated significantly for the cyclins B1, D3, and E. A statistically significant relation was observed between overexpression of cyclin A2 and local relapse of rectal carcinomas, as higher expression of cyclin A2 was associated with lower local recurrence rate.

  12. Differences in Protein Expression and Gene Amplification of Cyclins between Colon and Rectal Adenocarcinomas

    Directory of Open Access Journals (Sweden)

    Rolf Aamodt

    2009-01-01

    Full Text Available Adenocarcinomas of rectum and colon may be different with regard to the cellular biological basis for cancer development. A material of 246 rectal cancers removed surgically at Akershus University Hospital in the years 1992–2000 was investigated and was compared to a material of 219 colon cancers operated on at Akershus University Hospital during the years 1988, 1990 and 1997–2000. There were highly significant differences between the rectal and the colon cancers in the protein expression of cyclin D1, cyclin D3, cyclin E, nuclear β-catenin, and c-Myc and in gene amplification of cyclin A2, cyclin B1, cyclin D1, and cyclin E. Gene amplification and protein expression in the rectal cancers correlated significantly for the cyclins B1, D3, and E. A statistically significant relation was observed between overexpression of cyclin A2 and local relapse of rectal carcinomas, as higher expression of cyclin A2 was associated with lower local recurrence rate.

  13. Acute onset and rapid progression of multiple organ failure in a young adult with undiagnosed disseminated colonic adenocarcinoma

    DEFF Research Database (Denmark)

    Frestad, Daria; Perner, Anders; Pedersen, Ulf Gøttrup

    2014-01-01

    , ascites and multiple vein thrombosis. The patient passed away shortly after admission due to treatment-resistant tumour lysis syndrome and multiple organ failure. Biopsy results revealed disseminated adenocarcinoma of the colon, with metastases to lymph nodes, liver, lungs and pleura. CRC in younger...

  14. Adenocarcinoma of the Right Colon in a Patient with Bloom Syndrome.

    Science.gov (United States)

    Martinez, Carlos Augusto Real; Pinheiro, Lilian Vital; Rossi, Debora Helena; Camargo, Michel Gardere; Ayrizono, Maria de Lourdes Setsuko; Leal, Raquel Franco; Coy, Cláudio Saddy Rodrigues

    2016-01-01

    Introduction. Bloom syndrome (BS) is an inherited disorder due to mutation in BLM gene. The diagnosis of BS should be considered in patients with growth retardation of prenatal onset, a photosensitive rash in a butterfly distribution over the cheeks, and an increased risk of cancer at an early age. Clinical manifestations also include short stature, dolichocephaly, prominent ears, micrognathia, malar hypoplasia and a high-pitched voice, immunodeficiency, type II diabetes, and hypogonadism associated with male infertility and female subfertility. The aim of this report is to describe case of patient with BS who developed adenocarcinoma of the cecum, successfully treated by right colectomy. Case Report. A 40-year-old man underwent colonoscopy to investigate the cause of his diarrhea, weight loss, and anemia. The patient knew that he was a carrier of BS diagnosed at young age. The colonoscopy showed an expansive and vegetating mass with 5.5 cm in diameter, located within the ascending colon. Histopathological analysis of tissue fragments collected during colonoscopy confirmed the presence of tubular adenocarcinoma, and he was referred for an oncological right colectomy. The procedure was performed without complications, and the patient was discharged on the fifth postoperative day. Histopathological examination of the surgical specimen confirmed the presence of a grade II tubular adenocarcinoma (stage IIA). The patient is currently well five years after surgery, without clinical or endoscopic signs of relapse in a multidisciplinary approach for the monitoring of comorbidities related to BS. Conclusion. Despite the development of colorectal cancer to be, a possibility rarely described the present case shows the need for early screening for colorectal cancer in all patients affected by BS.

  15. Adenocarcinoma of the Right Colon in a Patient with Bloom Syndrome

    Directory of Open Access Journals (Sweden)

    Carlos Augusto Real Martinez

    2016-01-01

    Full Text Available Introduction. Bloom syndrome (BS is an inherited disorder due to mutation in BLM gene. The diagnosis of BS should be considered in patients with growth retardation of prenatal onset, a photosensitive rash in a butterfly distribution over the cheeks, and an increased risk of cancer at an early age. Clinical manifestations also include short stature, dolichocephaly, prominent ears, micrognathia, malar hypoplasia and a high-pitched voice, immunodeficiency, type II diabetes, and hypogonadism associated with male infertility and female subfertility. The aim of this report is to describe case of patient with BS who developed adenocarcinoma of the cecum, successfully treated by right colectomy. Case Report. A 40-year-old man underwent colonoscopy to investigate the cause of his diarrhea, weight loss, and anemia. The patient knew that he was a carrier of BS diagnosed at young age. The colonoscopy showed an expansive and vegetating mass with 5.5 cm in diameter, located within the ascending colon. Histopathological analysis of tissue fragments collected during colonoscopy confirmed the presence of tubular adenocarcinoma, and he was referred for an oncological right colectomy. The procedure was performed without complications, and the patient was discharged on the fifth postoperative day. Histopathological examination of the surgical specimen confirmed the presence of a grade II tubular adenocarcinoma (stage IIA. The patient is currently well five years after surgery, without clinical or endoscopic signs of relapse in a multidisciplinary approach for the monitoring of comorbidities related to BS. Conclusion. Despite the development of colorectal cancer to be, a possibility rarely described the present case shows the need for early screening for colorectal cancer in all patients affected by BS.

  16. COLONIC ADENOCARCINOMAS IN A FAMILIAL GROUP OF CAPTIVE AMUR RAT SNAKES (ELAPHE SCHRENCKI).

    Science.gov (United States)

    Lamglait, Benjamin; Lemberger, Karin

    2017-06-01

    This article reports five cases of colonic adenocarcinomas in a family group of captive Amur rat snake (Elaphe schrenckii) from the Réserve Africaine de Sigean, France. This tumor was detected in three females and two males, all adults, and accounted for 16% of causes of death of adults of this species at this institution from 1986 to 2013. Grossly, mild to marked thickening of the intestinal wall cranially to the cloaca was found in four cases; tan to yellow firm masses were noted in the distal intestinal wall in the other case. Microscopically, neoplasms were characterized by infiltrating, poorly circumscribed, and unencapsulated nests of epithelial cells. Marked anisokaryosis and anisocytosis were seen in all neoplasms. The etiology of the neoplasms was not determined, but the familial clustering suggests a common etiologic factor.

  17. Role of coagulation in the recruitment of colon adenocarcinoma cells to thrombus under shear.

    Science.gov (United States)

    Baker-Groberg, Sandra M; Itakura, Asako; Gruber, András; McCarty, Owen J T

    2013-11-01

    Colorectal cancer metastases can appear on the peritoneum and in lymph nodes, liver, and lungs, suggesting both hematogenous and lymphatic spreading of the primary tumor. While antithrombotic agents have been shown to reduce both long-term incidence and metastasis, the role of coagulation in facilitating metastasis is ill defined. We investigated the kinetics and molecular mechanisms of metastatic colon adenocarcinoma cell recruitment to thrombi under shear flow, ex vivo. Platelet aggregates were formed by perfusing citrated anticoagulated whole blood over immobilized fibrinogen or fibrillar collagen. Thrombi were formed by perfusing recalcified whole blood over fibrinogen or fibrillar collagen in the presence of coagulation. Cultured colon adenocarcinoma cells (SW620) were perfused either during or following platelet aggregate or thrombus formation. The degree of transient tumor cell interactions (recruitment, rolling, and release) and the number of firmly adhered tumor cells were quantified using fluorescence microscopy. Platelet aggregates and thrombi formed on either fibrinogen- or fibrillar-collagen supported SW620 cell interactions and adhesion under shear. Thrombi or fibrin supported a greater degree of SW620 cell interactions and adhesion compared with platelet aggregates or fibrinogen, respectively, demonstrating that coagulation promoted SW620 cell recruitment under shear. Interestingly, in the absence of anticoagulation, we observed SW620 preferentially binding to thrombus-bound polymorphonuclear leukocytes (PMNs). The addition of purified PMNs to thrombi resulted in a doubling of the number of interacting and bound SW620 cells. Since thrombi often accumulate and activate leukocytes, our findings suggest that leukocytes may play a role in localizing metastases to sites of thrombogenesis.

  18. The prevalence of human papillomavirus in colorectal adenomas and adenocarcinomas

    DEFF Research Database (Denmark)

    Baandrup, Louise; Thomsen, Louise T; Olesen, Tina Bech

    2014-01-01

    The role of human papillomavirus (HPV) in colorectal cancer has been widely studied with conflicting results. We performed a systematic review and a meta-analysis to estimate the prevalence of HPV in colorectal adenocarcinomas and adenomas, and test the potential association....

  19. Synchronous Gastric Gastrointestinal Stromal Tumor and Colon Adenocarcinoma: A Case Report

    Directory of Open Access Journals (Sweden)

    Thivi Vasilakaki

    2014-01-01

    Full Text Available Gastrointestinal stromal tumors (GISTs represent the majority of primary mesenchymal tumors of the gastrointestinal tract. They are generally considered to be solitary tumors and therefore the synchronous occurrence with other primary malignancies of gastrointestinal track is considered a rare event. Here we present the case of a 75-year-old man admitted to our hospital with a 10-day history of gastrointestinal bleeding. Colonoscopy revealed an ulcerative mass of 4 cm in diameter in the ascending colon. Gastroscopy revealed a bulge in the gastric body measuring 1 cm in diameter with normal overlying mucosa. Surgical intervention was suggested and ileohemicolectomy with regional lymph node resection along with gastric wedge resection was performed. Pathologic examination of the ascending colon mass showed an invasive moderately differentiated adenocarcinoma stage III B (T3N1M0. Grossly resected wedge of stomach showed a well circumscribed intramural tumor which microscopically was consistent with essentially benign gastrointestinal stromal tumor (according to Miettinen criteria. The patient did not receive additional treatment. Two years later the patient showed no evidence of recurrence or metastasis.

  20. Marriage is a dependent risk factor for mortality of colon adenocarcinoma without a time-varying effect.

    Science.gov (United States)

    Liu, Minling; Li, Lixian; Yu, Wei; Chen, Jie; Xiong, Weibin; Chen, Shuang; Yu, Li

    2017-03-21

    It has been well recognized that the effects of many prognostic factors could change during long-term follow-up. Although marriage has been proven to be a significant prognostic factor for the survival of colon cancer, whether the effect of marriage is constant with time remain unknown. This study analyzed the impact of marital status on the mortality of colon cancer patients with an extended Cox model that allowed for time-varying effects. We identified 71,955 patients who underwent colectomy between 2004 and 2009 to treat colon adenocarcinoma from the Surveilance, Epidemiology and End Results Database. The multivariate extended Cox model was used to evaluate the effect of marital status on all-cause mortality, while the Fine-Gray competing risks model was used for colon cancer-specific mortality, with death from other causes as the competing risk. The unmarried patients carried a 1.37-fold increased risk of all-cause mortality compared with the married patients (95%CI: 1.33-1.40; peffects on survival. Marriage is a dependent prognosis factor for survival of surgically treated colon adenocarcinoma patients. Psychological interventions are suggested to improve receipt of treatment among unmarried patients, as their poor survival may be due to the inefficient treatment.

  1. Urotensin-II receptor is over-expressed in colon cancer cell lines and in colon carcinoma in humans.

    Science.gov (United States)

    Federico, Alessandro; Zappavigna, Silvia; Romano, Marco; Grieco, Paolo; Luce, Amalia; Marra, Monica; Gravina, Antonietta Gerarda; Stiuso, Paola; D'Armiento, Francesco Paolo; Vitale, Giovanni; Tuccillo, Concetta; Novellino, Ettore; Loguercio, Carmela; Caraglia, Michele

    2014-01-01

    Urotensin (U)-II receptor (UTR) has been previously reported to be over-expressed in a number of tumours. Whether UTR-related pathway plays a role in colon carcinogenesis is unknown. We evaluated UTR protein and mRNA expression in human epithelial colon cancer cell lines and in normal colon tissue, adenomatous polyps and colon cancer. U-II protein expression was assessed in cancer cell lines. Moreover, we evaluated the effects of U-II(4-11) (an UTR agonist), antagonists and knockdown of UTR protein expression through a specific shRNA, on proliferation, invasion and motility of human colon cancer cells. Cancer cell lines expressed U-II protein and UTR protein and mRNA. By immunohistochemistry, UTR was expressed in 5-30% of epithelial cells in 45 normal controls, in 30-48% in 21 adenomatous polyps and in 65-90% in 48 colon adenocarcinomas. UTR mRNA expression was increased by threefold in adenomatous polyps and eightfold in colon cancer, compared with normal colon. U-II(4-11) induced a 20-40% increase in cell growth while the blockade of the receptor with specific antagonists caused growth inhibition of 20-40%. Moreover, the knock down of UTR with a shRNA or the inhibition of UTR with the antagonist urantide induced an approximately 50% inhibition of both motility and invasion. UTR appears to be involved in the regulation of colon cancer cell invasion and motility. These data suggest that UTR-related pathway may play a role in colon carcinogenesis and that UTR may function as a target for therapeutic intervention in colon cancer. © 2013 Stichting European Society for Clinical Investigation Journal Foundation.

  2. Metastatic adenocarcinoma of the colon presenting as a monarthritis of the hip in a young patient

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    Cobiella Carlos

    2006-12-01

    Full Text Available Abstract Background Malignant arthritis is a rare manifestation of metastatic disease. We describe the case of a previously well 28 year old man in whom hip pain was the presenting symptom of disease. We describe the case and discuss the aetiology of colorectal cancer in young patients. We then review the literature and discuss the investigation and management of malignant joint arthritis. Case presentation We present the case of a 28 year old man who presented to the emergency department with an acute monoarthritis of the hip. He had an unremarkable past medical history and was systemically well. A diagnosis of malignant joint effusion was reached after a heightened index of clinical suspicion, magnetic resonance imaging and cytological evaluation of the synovial fluid. Computed tomography and bone scan confirmed widespread metastatic disease from a primary colonic adenocarcinoma. The patient tolerated three cycles of oxaliplatin and capecitabine but died 4 months after presentation. Conclusion The metastatic spread of cancer to the joint and the synovium is one of the rarest manifestations of malignant disease and has not been previously reported as the presenting symptom of disease. The diagnosis is a difficult one to reach and is associated with a poor prognosis. This case illustrates the importance of thorough investigation in reaching this diagnosis and entertaining the possibility in individuals who do not respond to conventional management of acute monoarthritis, even in young patients and individuals who do not display any other symptoms of disease.

  3. Characterization of Cancer Stem Cells in Colon Adenocarcinoma Metastasis to the Liver.

    Science.gov (United States)

    Humphries, Hugo N; Wickremesekera, Susrutha K; Marsh, Reginald W; Brasch, Helen D; Mehrotra, Shreeja; Tan, Swee T; Itinteang, Tinte

    2017-01-01

    Fifty percent of colorectal cancer (CRC) patients develop liver metastasis. This study identified and characterized cancer stem cells (CSCs) within colon adenocarcinoma metastasis to the liver (CAML). 3,3-Diaminobenzidine immunohistochemical (IHC) staining was performed on nine CAML samples for embryonic stem cell (ESC) markers OCT4, SOX2, NANOG, c-Myc, and KLF4. Immunofluorescence (IF) IHC staining was performed to investigate coexpression of two markers. NanoString mRNA expression analysis and colorimetric in situ hybridization (CISH) were performed on four snap-frozen CAML tissue samples for transcript expression of these ESC markers. Cells stained positively and negatively for each marker by IHC and CISH staining were counted and analyzed. 3,3-Diaminobenzidine IHC staining, and NanoString and CISH mRNA analyses demonstrated the expression of OCT4, SOX2, NANOG, c-Myc, and KLF4 within in all nine CAML samples, except for SOX2 which was below detectable levels on NanoString mRNA analysis. IF IHC staining showed the presence of a SOX2 + /NANOG + /KLF4 + /c-Myc + /OCT - CSC subpopulation within the tumor nests, and a SOX2 + /NANOG + /KLF4 + /c-Myc + /OCT4 - CSC subpopulation and a SOX2 + /NANOG + /KLF4 + /c-Myc + /OCT4 + CSC subpopulation within the peritumoral stroma. The novel finding of three CSC subpopulations within CAML provides insights into the biology of CRC.

  4. Clotrimazole decreases glycolysis and the viability of lung carcinoma and colon adenocarcinoma cells.

    Science.gov (United States)

    Penso, Julia; Beitner, Rivka

    2002-09-20

    Glycolysis is known to be the primary energy source in most cancer cells. We investigated here the effect of clotrimazole (1-(alpha-2-chlorotrityl)imidazole), the antifungal azole derivative, which was recently recognized as calmodulin antagonist, on the levels of glucose 1,6-bisphosphate and fructose 1,6-bisphosphate, the two stimulatory signal molecules of glycolysis, and on ATP content and cell viability in LL/2 Lewis lung carcinoma cells and CT-26 colon adenocarcinoma cells. We found that clotrimazole induced a significant, dose- and time-dependent reduction in the levels of glucose 1,6-bisphosphate, fructose 1,6-bisphosphate, ATP, and cell viability. These findings suggest that clotrimazole causes a reduction in glycolysis and ATP levels, which eventually leads to cell destruction after 3 h of treatment. Since cell proliferation was also reported to be inhibited by calmodulin antagonists, this substance is most promising agent in treatment of cancer by inhibiting both cell proliferation and the glycolytic supply of ATP required for cancer cell growth. Copyright 2002 Elsevier Science B.V.

  5. Myxoma virus is oncolytic for human pancreatic adenocarcinoma cells.

    Science.gov (United States)

    Woo, Yanghee; Kelly, Kaitlyn J; Stanford, Marianne M; Galanis, Charles; Chun, Yun Shin; Fong, Yuman; McFadden, Grant

    2008-08-01

    Viral oncolytic therapy, which seeks to exploit the use of live viruses to treat cancer, has shown promise in the treatment of cancers resistant to conventional anticancer therapies. Among the most difficult to treat cancers is advanced pancreatic adenocarcinoma. Our study investigates the ability of a novel oncolytic agent, myxoma virus, to infect, productively replicate in, and kill human pancreatic cancer cells in vitro. The myxoma virus vMyxgfp was tested against a panel of human pancreatic adenocarcinoma cell lines. Infectivity, viral proliferation, and tumor cell kill were assessed. Infection of tumor cells was assessed by expression of the marker gene enhanced green fluorescent protein (e-GFP). vMyxgfp had the ability to infect all pancreatic cancer cell lines tested. Killing of tumor cells varied among the 6 cell lines tested, ranging from >90% cell kill at 7 days for the most sensitive Panc-1 cells, to 39% in the most resistant cell line Capan-2. Sensitivity correlated to replication of virus, and was found to maximally exhibit a four-log increase in foci-forming units for the most sensitive Panc-1 cells within 72 h. Our study demonstrates for the first time the ability of the myxoma virus to productively infect, replicate in, and lyse human pancreatic adenocarcinoma cells in vitro. These data encourage further investigation of this virus, which is pathogenic only in rabbits, for treatment of this nearly uniformly fatal cancer.

  6. Cutaneous metastases from colonic adenocarcinoma: case report Metástase cutânea de adenocarcinoma de cólon: relato de caso

    Directory of Open Access Journals (Sweden)

    Caroline Merci Caliari de Neves Gomes

    2012-09-01

    Full Text Available The presence of cutaneous metastases (CM from a digestive tract cancer is infrequent, appearing in less than 5% of the cases. Given the low incidence of metastasis from colon adenocarcinoma, an unusual case that occurred in the Colorectal Surgery Department of Santa Casa de São Paulo is described in this report, and a brief review of literature is presented. A 78-year-old female patient who underwent right hemicolectomy, developed a tumor with approximately 8 cm in diameter in her gluteus eight months later, which was surgically resected, and the histological diagnosis was metastatic adenocarcinoma of the right colon. Although the literature estimated short survival in cases of CM, the patient developed no signs of tumor recurrence five months after the onset of metastasis in the gluteus, with significant improvement in her quality of life.A presença de metástase cutânea (MC de neoplasia de trato digestivo é um evento pouco frequente, presente em menos de 5% dos casos da doença. Tendo em vista a baixa incidência da metástase cutânea de adenocarcinoma de cólon, será descrito no presente relato um caso incomum que ocorreu no Serviço de Coloproctologia do Departamento de Cirurgia da Irmandade da Santa Casa de São Paulo e será feita uma breve revisão de literatura. Uma paciente do sexo feminino, 78 anos, submetida à hemicolectomia direita, desenvolveu após oito meses tumoração de aproximadamente 8 cm de diâmetro em sua nádega, que foi ressecada cirurgicamente, tendo diagnóstico histológico de metástase de adenocarcinoma de cólon direito. Apesar de ser estimada pela literatura uma sobrevida curta nos casos de MC, a paciente evolui sem sinais de recidiva do tumor após cinco meses do surgimento da metástase em glúteo, com melhora significativa em sua qualidade de vida.

  7. Cystadenocarcinoma of the appendix: an incidental imaging finding in a patient with adenocarcinomas of the ascending and the sigmoid colon

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    Prassopoulos Panos

    2003-10-01

    Full Text Available Abstract Background Primary adenocarcinomas of the appendix are uncommon. Mucoceles that result from mucinous adenocarcinomas of the appendix may be incidentally detected on imaging. Case presentation A case of a mucocele of the appendix, due to cystadenocarcinoma, is presented as an incidental imaging finding in a female, 86-year-old patient. The patient was admitted due to rectal hemorrhage and underwent colonoscopy, x-ray, US and CT. Adenocarcinoma of the ascending colon, adenomatous polyp of the sigmoid colon and a cystic lesion in the right iliac fossa were diagnosed. The cystic lesion was characterized as mucocele. The patient underwent right hemicolectomy, excision of the mucocele and sigmoidectomy. She recovered well and in two-year follow-up is free from cancer. Conclusions Preoperative diagnosis of an underlying malignancy in a mucocele is important for patient management, but it is difficult on imaging studies. Small lymph nodes or soft tissue stranding in the surrounding fat on computed tomography examination may suggest the possibility of malignancy.

  8. Characterization of Cancer Stem Cells in Colon Adenocarcinoma Metastasis to the Liver

    Directory of Open Access Journals (Sweden)

    Hugo N. Humphries

    2018-01-01

    Full Text Available BackgroundFifty percent of colorectal cancer (CRC patients develop liver metastasis. This study identified and characterized cancer stem cells (CSCs within colon adenocarcinoma metastasis to the liver (CAML.Methods3,3-Diaminobenzidine immunohistochemical (IHC staining was performed on nine CAML samples for embryonic stem cell (ESC markers OCT4, SOX2, NANOG, c-Myc, and KLF4. Immunofluorescence (IF IHC staining was performed to investigate coexpression of two markers. NanoString mRNA expression analysis and colorimetric in situ hybridization (CISH were performed on four snap-frozen CAML tissue samples for transcript expression of these ESC markers. Cells stained positively and negatively for each marker by IHC and CISH staining were counted and analyzed.Results3,3-Diaminobenzidine IHC staining, and NanoString and CISH mRNA analyses demonstrated the expression of OCT4, SOX2, NANOG, c-Myc, and KLF4 within in all nine CAML samples, except for SOX2 which was below detectable levels on NanoString mRNA analysis. IF IHC staining showed the presence of a SOX2+/NANOG+/KLF4+/c-Myc+/OCT− CSC subpopulation within the tumor nests, and a SOX2+/NANOG+/KLF4+/c-Myc+/OCT4− CSC subpopulation and a SOX2+/NANOG+/KLF4+/c-Myc+/OCT4+ CSC subpopulation within the peritumoral stroma.ConclusionThe novel finding of three CSC subpopulations within CAML provides insights into the biology of CRC.

  9. Early-Onset Signet-Ring Cell Adenocarcinoma of the Colon: A Case Report and Review of the Literature

    Directory of Open Access Journals (Sweden)

    Maliha Khan

    2017-01-01

    Full Text Available Colorectal cancer (CRC remains the second leading cause of cancer-related deaths in the United States. While a decline has been observed in the older population, the occurrence of CRC in the adolescent and young adult (AYA population has increased over the past two decades. The histopathologic characteristics and clinical behavior of CRC in AYA patients have been shown to be distinct from those of CRC in older adults. The rarer subtypes of CRC such as mucinous adenocarcinoma and signet-ring cell carcinoma are associated with a poorer prognosis compared to the more common subtypes. Here we report a case of a 20-year-old man who was diagnosed with stage IVB (T4 N2 M1, with peritoneal carcinomatosis signet-ring cell adenocarcinoma of the colon. The scarcity of information on these rarer subtypes merits further study and investigation.

  10. Acta Medica Indonesiana - The Indonesian Journal of Internal Medicine 333 Supraclavicular Lymphnodes: Unusual Manifestation of Metastase Adenocarcinoma Colon

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    Harijono Achmad

    2015-12-01

    Full Text Available We report a patient with supraclavicular lymph node metastasis from an undetectable adenocarcinoma of the transverse colon, who presented with cough and was diagnosed with typhoid fever, bronchitis as well as liver metastasis. There were an abdominal fullness, weight loss, constipation, pencil-like stool with mucous and blood, low-grade fever, bone ache, and tea-color urine. The first colonoscopy revealed lymphocytic ileitis and microscopic findings also showed lymphocytic ileitis. Abdominal USG and CT revealed liver metastasis of unknown origin. Based on the clinical sign and symptoms, we suspected that colorectal carcinoma was the primary site. Then, the second colonoscopy was performed and it revealed a small polyp, which was followed with a biopsy and the result supported a well-differentiated colon adenocarcinoma. Similar result was also revealed by the histopathological evaluation. This is an unusual case of liver and supraclavicular lymph node metastasis arising from a small polyp adenocacinoma of the transverse colon. Key words: liver metastase, colorectal carcinoma, lymph node.

  11. Adenocarcinoma mucoproductor de colon con infiltración de estómago y metástasis ováricas (tumor de Krukenberg Colon mucoproducing adenocarcinoma with stomach infiltration and ovarian metastases (Krukenberg's tumor

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    Orestes Noel Mederos Curbelo

    2011-12-01

    Full Text Available Se presenta una paciente femenina de 29 años, operada de urgencia por presentar un gran tumor que incluía cuerpo gástrico y colon trasverso, con una perforación gástrica. Se realizó una gastrectomía subtotal con colectomía trasversa en bloque que incluyó el epiplón mayor. El diagnóstico histológico fue adenocarcinoma túbulo papilar mucoproductor de origen colónico, que infiltra hasta la serosa y pared gástrica. Se realizó tratamiento adyuvante con poliquimioterapia. Diez meses después presenta un tumor en hipogastrio, que al tacto vaginal, correspondía a los órganos genitales, sospecha clínica que confirman el ultrasonido abdominal y la tomografía axial computarizada. El hallazgo transoperatorio fueron tumores voluminosos de ambos ovarios, y otro tumor que afectaba la unión rectosigmoide. Se realizó una histerectomía radical con ooforectomía bilateral y sigmoidectomía, se reseca la porción proximal del recto, y se cierra tipo Hartman. El diagnóstico histológico final fue metástasis en serosa uterina e intestinal, y en ambos ovarios de adenocarcinoma mucoproductor, túbulo papilar de intestino previamente diagnosticado (tumor de Krukenberg. Se complementó el tratamiento con poliquimioterapia adyuvante.This is the case of a woman aged 29 operated on of emergency due to a tumor involving gastric body and transverse colon with gastric perforation. A subtotal gastrectomy with block transverse colectomy including the greater omentum was carried out. The histological diagnosis was a mucoproducing papillary tubular adenocarcinoma of colonic origin infiltrating to serosa and gastric wall. An adjuvant treatment was applied with poly-chemotherapy. Ten months later appears a hypogastric tumor which at vaginal manual examination corresponding to genital organs, clinical suspicion confirmed by abdominal ultrasound and computerized axial tomography. The transoperative findings were bulky tumors of both ovaries and another tumor

  12. Tumores de cólon - primeiro achado do adenocarcinoma de pâncreas: relato de caso Colon tumors - first find of the pancreatic adenocarcinoma: case report

    Directory of Open Access Journals (Sweden)

    Sandra Pedroso de Moraes

    2007-09-01

    malnourished, with abdominal distention and diffuse abdominal pain on clinical examination. Laboratorial exams showed hyperglycemia, x-ray revealed intense abdominal distention, abdominal ultrasound revealed cholecystolithiasis and upper digestive endoscopy showed pangastritis. The computed tomography just confirmed the cholecystolithiasis. A colonoscopy was performed and revealed three tumors located in the rectum, transverse colon and ileocecal valve that were biopsed and just showed inflammatory cells. As the symptoms persist he underwent laparoscopic cholecystectomy that was converted to the open technique when it was observed white flat lesions in the diaphragm peritoneum, the biopsies revealed adenocarcinoma. In the fifth postoperatory day the patient developed obstructive symptoms and underwent right colectomy with double terminal colostomy and pancreas biopsy that showed adenocarcinoma with immunohistochemical profile proving the pancreas as the source. The patient died within one month. CONCLUSION: The normal findings in radiological exams do not dismiss a diagnostic hypothesis and when the source of a tumor is not well established the clinical patterns should be considered and the immunohistochemical profile is essential to confirm the diagnosis.

  13. FXR silencing in human colon cancer by DNA methylation and KRAS signaling.

    Science.gov (United States)

    Bailey, Ann M; Zhan, Le; Maru, Dipen; Shureiqi, Imad; Pickering, Curtis R; Kiriakova, Galina; Izzo, Julie; He, Nan; Wei, Caimiao; Baladandayuthapani, Veerabhadran; Liang, Han; Kopetz, Scott; Powis, Garth; Guo, Grace L

    2014-01-01

    Farnesoid X receptor (FXR) is a bile acid nuclear receptor described through mouse knockout studies as a tumor suppressor for the development of colon adenocarcinomas. This study investigates the regulation of FXR in the development of human colon cancer. We used immunohistochemistry of FXR in normal tissue (n = 238), polyps (n = 32), and adenocarcinomas, staged I-IV (n = 43, 39, 68, and 9), of the colon; RT-quantitative PCR, reverse-phase protein array, and Western blot analysis in 15 colon cancer cell lines; NR1H4 promoter methylation and mRNA expression in colon cancer samples from The Cancer Genome Atlas; DNA methyltransferase inhibition; methyl-DNA immunoprecipitation (MeDIP); bisulfite sequencing; and V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) knockdown assessment to investigate FXR regulation in colon cancer development. Immunohistochemistry and quantitative RT-PCR revealed that expression and function of FXR was reduced in precancerous lesions and silenced in a majority of stage I-IV tumors. FXR expression negatively correlated with phosphatidylinositol-4, 5-bisphosphate 3 kinase signaling and the epithelial-to-mesenchymal transition. The NR1H4 promoter is methylated in ~12% colon cancer The Cancer Genome Atlas samples, and methylation patterns segregate with tumor subtypes. Inhibition of DNA methylation and KRAS silencing both increased FXR expression. FXR expression is decreased early in human colon cancer progression, and both DNA methylation and KRAS signaling may be contributing factors to FXR silencing. FXR potentially suppresses epithelial-to-mesenchymal transition and other oncogenic signaling cascades, and restoration of FXR activity, by blocking silencing mechanisms or increasing residual FXR activity, represents promising therapeutic options for the treatment of colon cancer.

  14. Metallothionein in human oesophagus, Barrett's epithelium and adenocarcinoma

    OpenAIRE

    Coyle, P.; Mathew, G; Game, P A; Myers, J C; Philcox, J C; Rofe, A M; Jamieson, G G

    2002-01-01

    The potential of the metal-binding protein, metallothionein, in assessing the progression of normal oesophagus through Barrett's to adenocarcinoma was investigated. Metallothionein was quantitatively determined in resected tissues from patients undergoing oesophagectomy for high grade dysplasia/adenocarcinoma and in biopsies from patients with Barrett's syndrome. In 10 cancer patients, metallothionein concentrations in adenocarcinoma were not significantly different from normal oesophagus, al...

  15. K-RAS point mutation, and amplification of C-MYC and C-ERBB2 in colon adenocarcinoma.

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    Tadeusz Pawełczyk

    2004-10-01

    Full Text Available The routine multidisciplinary management of colon cancer is based mainly on tumor staging, histology, grading and vascular invasion. In this approach, important individual information derived from molecular characteristics of the tumor may be missed, especially since significant heterogeneity of molecular aberrations in cancer cells has been observed, and recognition of every of relationships between them may be of value. K-RAS, C-MYC and C-ERBB2 are protooncogenes taking part in carcinogenesis and tumor progression in the colon. They influence cell proliferation, differentiation and survival. K-RAS point mutation, as well as amplification of C-MYC and C-ERBB2 were searched in 84 primary colon adenocarcinomas resected with curative intent. Multiplex polymerase-chain reaction and restriction fragment length polymorphism were performed to assess codon 12 K-RAS point mutation. Amplification of C-MYC and C-ERBB2 genes was evaluated by densitometry after agarose gel separation of the respective multiplex PCR products. No relation was found among mutated and/or amplified genes, and between searched molecular aberrations and pathoclinical features. In multivariate analysis, nodal status appeared to be the only independent prognostic indicator. In colon adenocarcinoma, codon 12 K-RAS point mutation and amplification of C-MYC and C-ERBB2 seem to occur independently in the process of tumor progression. Amplification of C-ERBB2 tends to associate with more advanced stage of disease. Concomitant occurrence of codon 12 K-RAS mutation, C-MYC and C-ERBB2 amplification was of no prognostic value in respect to survival.

  16. The clinical significances of the abnormal expressions of Piwil1 and Piwil2 in colonic adenoma and adenocarcinoma

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    Wang HL

    2015-05-01

    Full Text Available Hai-Ling Wang,1 Bei-Bei Chen,1 Xin-Guang Cao,1 Jin Wang,2 Xiu-Feng Hu,1 Xiao-Qian Mu,1 Xiao-Bing Chen1 1The Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, People’s Republic of China; 2The First Affiliated Hospital of Zhengzhou University, Zhengzhou, People’s Republic of China Objective: The objective of the present investigation was to study the clinical significances of the abnormal expressions of Piwil1 and Piwil2 protein in colonic adenoma and adenocarcinoma.Methods: This study had applied immunohistochemical method to detect 45 cases of tissues adjacent to carcinoma (distance to cancerous tissue was above 5 cm, 41 cases of colonic adenoma and 92 cases of colon cancer tissues, and their Piwil1 and Piwil2 protein expression levels.Analysis: The correlation of both expression and its relationship with clinicopathological features of colon cancer was analyzed.Results: Positive expression rates of Piwil1 in tissues adjacent to carcinoma, colonic adenoma, and colon cancer were 11.1% (5/45, 53.7% (22/41, and 80.4% (74/92, respectively; the expression rates increased, and the comparisons between each two groups were statistically significant (P<0.05. In each group, the positive expression rates of Piwil2 were 24.4% (11/45 cases, 75.6% (31/41 cases, and 92.4% (85/92 cases; expression rates increased, and the comparisons between each two groups were statistically significant (P<0.05. Piwil1 expression and the correlation of the degree of differentiation, TNM stage, and lymph node metastasis were statistically significant (P<0.05. Piwil2 expression and the correlation of the degree of differentiation, tumor node metastasis (TNM stage, and lymph node metastasis had no statistical significance (P>0.05. In colon cancer tissue, Piwil1 and Piwil2 expressions were positively correlated (r=0.262, P<0.05.Conclusion: The results showed that the abnormal expression of Piwil1 and Piwil2 might play an important role in

  17. Differential expression proteomics of human colon cancer.

    Science.gov (United States)

    Mazzanti, Roberto; Solazzo, Michela; Fantappié, Ornella; Elfering, Sarah; Pantaleo, Pietro; Bechi, Paolo; Cianchi, Fabio; Ettl, Adam; Giulivi, Cecilia

    2006-06-01

    The focus of this study was to use differential protein expression to investigate operative pathways in early stages of human colon cancer. Colorectal cancer represents an ideal model system to study the development and progression of human tumors, and the proteomic approach avoids overlooking posttranslational modifications not detected by microarray analyses and the limited correlation between transcript and protein levels. Colon cancer samples, confined to the intestinal wall, were analyzed by expression proteomics and compared with matched samples from normal colon tissue. Samples were processed by two-dimensional gel electrophoresis, and spots differentially expressed and consistent across all patients were identified by matrix-assisted laser desorption ionization-time-of-flight mass spectrometry analyses and by Western blot analyses. After differentially expressed proteins and their metabolic pathways were analyzed, the following main conclusions were achieved for tumor tissue: 1) a shift from beta-oxidation, as the main source of energy, to anaerobic glycolysis was observed owed to the alteration of nuclear- versus mitochondrial-encoded proteins and other proteins related to fatty acid and carbohydrate metabolism; 2) lower capacity for Na(+) and K(+) cycling; and 3) operativity of the apoptosis pathway, especially the mitochondrial one. This study of the human colon cancer proteome represents a step toward a better understanding of the metabolomics of colon cancer at early stages confined to the intestinal wall.

  18. DNA Topoisomerase I-Targeted Chemotherapy of Human Colon Cancer in Xenografts

    Science.gov (United States)

    Giovanella, Beppino C.; Stehlin, John S.; Wall, Monroe E.; Wani, Mansukh C.; Nicholas, Allan W.; Liu, Leroy F.; Silber, Robert; Potmesil, Milan

    1989-11-01

    Drug development is needed to improve chemotherapy of patients with locally advanced or metastatic colon carcinoma, who otherwise have an unfavorable prognosis. DNA topoisomerase I, a nuclear enzyme important for solving topological problems arising during DNA replication and for other cellular functions, has been identified as a principal target of a plant alkaloid 20 (S)-camptothecin. Significantly increased concentrations of this enzyme, compared to that in normal colonic mucosa, were found in advanced stages of human colon adenocarcinoma and in xenografts of colon cancer carried by immunodeficient mice. Several synthetic analogs of camptothecin, selected by tests with the purified enzyme and tissue-culture screens, were evaluated in the xenograft model. Unlike other anticancer drugs tested, 20(RS)-9-amino-camptothecin (9-AC) induced disease-free remissions. The overall drug toxicity was low and allowed for repeated courses of treatment.

  19. Tryptophan autofluorescence imaging of neoplasms of the human colon

    Science.gov (United States)

    Banerjee, Bhaskar; Renkoski, Timothy; Graves, Logan R.; Rial, Nathaniel S.; Tsikitis, Vassiliki Liana; Nfonsom, Valentine; Pugh, Judith; Tiwari, Piyush; Gavini, Hemanth; Utzinger, Urs

    2012-01-01

    Detection of flat neoplasia is a major challenge in colorectal cancer screening, as missed lesions can lead to the development of an unexpected `incident' cancer prior to the subsequent endoscopy. The use of a tryptophan-related autofluorescence has been reported to be increased in murine intestinal dysplasia. The emission spectra of cells isolated from human adenocarcinoma and normal mucosa of the colon were studied and showed markedly greater emission intensity from cancerous cells compared to cells obtained from the surrounding normal mucosa. A proto-type multispectral imaging system optimized for ultraviolet macroscopic imaging of tissue was used to obtain autofluorescence images of surgical specimens of colonic neoplasms and normal mucosa after resection. Fluorescence images did not display the expected greater emission from the tumor as compared to the normal mucosa, most probably due to increased optical absorption and scattering in the tumors. Increased fluorescence intensity in neoplasms was observed however, once fluorescence images were corrected using reflectance images. Tryptophan fluorescence alone may be useful in differentiating normal and cancerous cells, while in tissues its autofluorescence image divided by green reflectance may be useful in displaying neoplasms.

  20. Adenocarcinoma of the Colon in a 10-year-old child

    African Journals Online (AJOL)

    by 1988, with less than 12 patients below the age of 10 years and the youngest nine months old at the time of diagnosis (2-11). Genetic instability without hereditary nonpolyposis colorectal cancer (HNPCC) is a major mechanism of causation (12,13). In contrast to adult patients, childhood adenocarcinoma is associated with.

  1. EGF-R is Expressed and AP-1 and NF-κ:B Are Activated in Stromal Myofibroblasts Surrounding Colon Adenocarcinomas Paralleling Expression of COX-2 and VEGF

    Science.gov (United States)

    Konstantinopoulos, Panagiotis A.; Vandoros, Gerasimos P.; Karamouzis, Michalis V.; Gkermpesi, Maria; Sotiropoulou-Bonikou, Georgia; Papavassiliou, Athanasios G.

    2007-01-01

    Background: COX-2 and VEGF are important triggers of colon cancer growth, metastasis and angiogenesis. Cox-2 promoter contains transcriptional regulatory elements for AP-1 and NF-κ:B transcription factors whilst vegf is a known AP-1 downstream target gene. We investigated whether stromal myofibroblasts surrounding colon adenocarcinomas express COX-2 and VEGF and whether activation of AP-1 and NF-κ:B, as well as expression of EGF-R parallel expression of COX-2 and VEGF in these cells. Methods: Immunohistochemical methodology was performed on archival sections from 40 patients with colon adenocarcinomas. We evaluated c-FOS, p-c-JUN (phosphorylated c-JUN), p-Iκ:B-α (phosphorylated Iκ:B-α), EGF-R, COX-2, NF-κ:B and VEGF expression in stromal myofibroblasts surrounding colon adenocarcinomas. Double immunostaining with a-smooth muscle actin and each antibody was done to verify the expression of these molecules in stromal myofibroblasts. Results: VEGF, p-Iκ:B-α, NF-κ:B, c-FOS, p-c-JUN, EGF-R and COX-2 were expressed in stromal myofibroblasts surrounding colon adenocarcinomas in the majority of cases. EGF-R, p-Iκ:B-α, NF-κ:B, c-FOS and p-c-JUN correlated positively with COX-2 and VEGF expression. Conclusion: Stromal myofibroblasts surrounding colon adenocarcinomas are an important source of VEGF and COX-2 production, while AP-1 and NF-κ:B transcription factors are activated and EGF-R is expressed in these cells and associated with COX-2 and VEGF production. PMID:18032824

  2. EGF-R is Expressed and AP-1 and NF-κ:B Are Activated in Stromal Myofibroblasts Surrounding Colon Adenocarcinomas Paralleling Expression of COX-2 and VEGF

    Directory of Open Access Journals (Sweden)

    Panagiotis A. Konstantinopoulos

    2007-01-01

    Full Text Available Background: COX-2 and VEGF are important triggers of colon cancer growth, metastasis and angiogenesis. Cox-2 promoter contains transcriptional regulatory elements for AP-1 and NF-κ:B transcription factors whilst vegf is a known AP-1 downstream target gene. We investigated whether stromal myofibroblasts surrounding colon adenocarcinomas express COX-2 and VEGF and whether activation of AP-1 and NF-κ:B, as well as expression of EGF-R parallel expression of COX-2 and VEGF in these cells. Methods: Immunohistochemical methodology was performed on archival sections from 40 patients with colon adenocarcinomas. We evaluated c-FOS, p-c-JUN (phosphorylated c-JUN, p-Iκ:B-α (phosphorylated Iκ:B-α, EGF-R, COX-2, NF-κ:B and VEGF expression in stromal myofibroblasts surrounding colon adenocarcinomas. Double immunostaining with a-smooth muscle actin and each antibody was done to verify the expression of these molecules in stromal myofibroblasts. Results: VEGF, p-Iκ:B-α, NF-κ:B, c-FOS, p-c-JUN, EGF-R and COX-2 were expressed in stromal myofibroblasts surrounding colon adenocarcinomas in the majority of cases. EGF-R, p-Iκ:B-α, NF-κ:B, c-FOS and p-c-JUN correlated positively with COX-2 and VEGF expression. Conclusion: Stromal myofibroblasts surrounding colon adenocarcinomas are an important source of VEGF and COX-2 production, while AP-1 and NF-κ:B transcription factors are activated and EGF-R is expressed in these cells and associated with COX-2 and VEGF production.

  3. Prehistoric human colonization of India

    Indian Academy of Sciences (India)

    Unknown

    versatile hand, and an unusually powerful brain, cultu- rally they differ in their ability to manufacture and ..... The explanation for this dramatic increase in human settlements lies in the increased rainfall and its effect on .... agriculture repertoire oats and another variety of wheat were added. There is evidence of stone bead ...

  4. Early human prostate adenocarcinomas harbor androgen-independent cancer cells.

    Directory of Open Access Journals (Sweden)

    Rita R Fiñones

    Full Text Available Although blockade of androgen receptor (AR signaling represents the main treatment for advanced prostate cancer (PrCa, many patients progress to a lethal phenotype of "Castration-Resistant" prostate cancer (CR-PrCa. With the hypothesis that early PrCa may harbor a population of androgen-unresponsive cancer cells as precursors to CR-recurrent disease, we undertook the propagation of androgen-independent cells from PrCa-prostatectomy samples of early, localized (Stage-I cases. A collection of 120 surgical specimens from prostatectomy cases was established, among which 54 were adenocarcinomas. Hormone-free cell culture conditions were developed allowing routine propagation of cells expressing prostate basal cell markers and stem/progenitor cell markers, and which proliferated as spheres/spheroids in suspension cultures. Colonies of androgen-independent epithelial cells grew out from 30/43 (70% of the adenocarcinoma cases studied in detail. Fluorescence microscopy and flow cytometry showed that CR-PrCa cells were positive for CD44, CD133, CK5/14, c-kit, integrin α2β1, SSEA4, E-Cadherin and Aldehyde Dehydrogenase (ALDH. All 30 CR-PrCa cell cultures were also TERT-positive, but negative for TMPRSS2-ERG. Additionally, a subset of 22 of these CR-PrCa cell cultures was examined by orthotopic xenografting in intact and castrated SCID mice, generating histologically typical locally-invasive human PrCa or undifferentiated cancers, respectively, in 6-8 weeks. Cultured PrCa cells and orthotopically-induced in vivo cancers lacked PSA expression. We report here the propagation of Cancer Initiating Cells (CIC directly from Stage I human PrCa tissue without selection or genetic manipulation. The propagation of stem/progenitor-like CR-PrCa cells derived from early human prostate carcinomas suggests the existence of a subpopulation of cells resistant to androgen-deprivation therapy and which may drive the subsequent emergence of disseminated CR-PrCa.

  5. Mucinous cystadenoma of the appendix associated with adenocarcinoma of the sigmoid colon and hepatocellular carcinoma of the liver: Report of a case

    Science.gov (United States)

    Djuranovic, Srdjan P; Spuran, Milan M; Kovacevic, Nada V; Ugljesic, Milenko B; Kecmanovic, Dragutin M; Micev, Marjan T

    2006-01-01

    Mucinous cystadenoma of the appendix is a rare condition and represents one of the three entities with the common name mucocele of the appendix. It is characterized by a cystic dilatation of the lumen with stasis of mucus inside it. Histopathologically mucocele is divided into three groups: focal or diffuse mucosal hyperplasia, mucinous cystadenoma and mucinous cystadenocarcinoma. This condition is often associated with other neoplasia, especially adenocarcinoma of the colon and ovaries. We here describe a 57 year old male patient who presented with abdominal discomfort, constipation, fresh blood in stool and frequent urination. He had a big cystadenoma of the appendix associated with adenocarcinoma of the colon and hepatocellular carcinoma of the liver. The patient underwent right haemicolectomy, sigmoid colon resection and segmental resection of the liver. Now 3 years later he has no evidence of disease relapse. According to this, we stress the need of accurate preoperative diagnosis and intraoperative exploration of the whole abdomen in these patients. PMID:16610012

  6. Chemopreventive efficacy of raloxifene, bexarotene and their combination on the progression of chemically-induced colon adenomas to adenocarcinomas in rats

    Science.gov (United States)

    Janakiram, Naveena B.; Mohammed, Altaf; Zhang, Yuting; Brewer, Misty; Bryant, Taylor; Lightfoot, Stan; Steele, Vernon E.; Rao, Chinthalapally V.

    2015-01-01

    Estrogen Receptor (ER)-β signaling is associated positively in colon tumor progression, whereas down-regulation or loss of function of retinoid X receptor (RXR)-α occurs in colon tumors. The chemopreventive efficacies of the estrogen antagonist raloxifene and the selective RXR agonist bexarotene were tested individually and in combination, during promotion and progression stages of colon tumorigenesis. Colon tumors were induced in male F344 rats with azoxymethane and at early adenoma stage, groups of rats (36 or 45/group) were fed diets containing raloxifene (1.5 or 3 ppm), bexarotene (50 or 100 ppm), or their low dose combinations for 40 weeks. Raloxifene or bexarotene alone significantly suppressed colon adenocarcinoma formation in terms of multiplicities (mean ± SE): control, 3.59 ± 0.25; 1.5 ppm raloxifene, 2.51 ± 0.29 (praloxifene, 2.14 ± 0.28 (praloxifene + 50 ppm bexarotene, 1.57 ± 0.21 (praloxifene, bexarotene and/or the combination showed significant suppression of proliferating cell nuclear antigen, cyclin D1 and β-catenin with an increased apoptotic cells (3-fold) and p21 expression (3.8-fold) as compared tumors of rats fed control diet. The combination of low doses of raloxifene and bexarotene significantly suppressed the progression of colonic adenomas to adenocarcinomas and may be useful for colon cancer prevention and/or treatment in high-risk individuals. PMID:24080207

  7. Isolation and in vitro expansion of human colonic stem cells

    NARCIS (Netherlands)

    Jung, P.; Sato, T.; Merlos-Suarez, A.; Barriga, F.M.; Iglesias, M.; Rossell, D.; Auer, H.; Gallardo, M.; Blasco, M.A.; Sancho, E.; Clevers, H.; Batlle, E.

    2011-01-01

    Here we describe the isolation of stem cells of the human colonic epithelium. Differential cell surface abundance of ephrin type-B receptor 2 (EPHB2) allows the purification of different cell types from human colon mucosa biopsies. The highest EPHB2 surface levels correspond to epithelial colonic

  8. Synchronous occurrence of colon adenocarcinoma and gastric schwannoma: case report and review of the literature.

    Science.gov (United States)

    Di Cataldo, Antonio; Trombatore, Claudia; Cocuzza, Aldo; Latino, Rosalia; Li Destri, Giovanni; Petrillo, Giuseppe

    2013-01-01

    We report a case of a 66-year-old man with a gastric schwannoma incidentally discovered during the treatment of a colon cancer. At the pre-operative computed tomography performed for the stadiation of the colonic tumor was incidentally noted the presence of a nodular tumor between the liver and the gastric wall. A wedge resection of this gastic tumor and the surgical resection of the left colon were performed all at once. The pathological examination of the gastric neoplasia revealed a picture consistent with gastric schwannoma. Gastrointestinal schwannomas are difficult but not impossible to diagnose preoperatively although they are often asymptomatic and radiologic findings are often nonspecific. Radiological features of Gastrointestinal schwannomas described in literature are reviewed. The treatment of choice is complete surgical excision with free margins because of diagnostic uncertainty, and the long-term outcome is excellent as these lesions are uniformly benign.

  9. The HSP90 Inhibitor Ganetespib Radiosensitizes Human Lung Adenocarcinoma Cells

    Energy Technology Data Exchange (ETDEWEB)

    Gomez-Casal, Roberto; Bhattacharya, Chitralekha [The University of Pittsburgh Cancer Institute, Pittsburgh, PA 15213 (United States); Department of Medicine, The University of Pittsburgh, Pittsburgh, PA 15213 (United States); Epperly, Michael W. [The University of Pittsburgh Cancer Institute, Pittsburgh, PA 15213 (United States); Department of Radiation Oncology, The University of Pittsburgh, Pittsburgh, PA 15213 (United States); Basse, Per H. [The University of Pittsburgh Cancer Institute, Pittsburgh, PA 15213 (United States); Department of Immunology, The University of Pittsburgh, Pittsburgh, PA 15213 (United States); Wang, Hong [The University of Pittsburgh Cancer Institute, Pittsburgh, PA 15213 (United States); Department of Biostatistics, The University of Pittsburgh, Pittsburgh, PA 15213 (United States); Wang, Xinhui [Harvard Medical School, Harvard University, 25 Shattuck Street, Boston, MA 02115 (United States); Proia, David A. [Synta Pharmaceuticals Corp., 45 Hartwell Avenue, Lexington, MA 02421 (United States); Greenberger, Joel S. [The University of Pittsburgh Cancer Institute, Pittsburgh, PA 15213 (United States); Department of Radiation Oncology, The University of Pittsburgh, Pittsburgh, PA 15213 (United States); Socinski, Mark A.; Levina, Vera, E-mail: levinav@upmc.edu [The University of Pittsburgh Cancer Institute, Pittsburgh, PA 15213 (United States); Department of Medicine, The University of Pittsburgh, Pittsburgh, PA 15213 (United States)

    2015-05-22

    The molecular chaperone HSP90 is involved in stabilization and function of multiple client proteins, many of which represent important oncogenic drivers in NSCLC. Utilization of HSP90 inhibitors as radiosensitizing agents is a promising approach. The antitumor activity of ganetespib, HSP90 inhibitor, was evaluated in human lung adenocarcinoma (AC) cells for its ability to potentiate the effects of IR treatment in both in vitro and in vivo. The cytotoxic effects of ganetespib included; G2/M cell cycle arrest, inhibition of DNA repair, apoptosis induction, and promotion of senescence. All of these antitumor effects were both concentration- and time-dependent. Both pretreatment and post-radiation treatment with ganetespib at low nanomolar concentrations induced radiosensitization in lung AC cells in vitro. Ganetespib may impart radiosensitization through multiple mechanisms: such as down regulation of the PI3K/Akt pathway; diminished DNA repair capacity and promotion of cellular senescence. In vivo, ganetespib reduced growth of T2821 tumor xenografts in mice and sensitized tumors to IR. Tumor irradiation led to dramatic upregulation of β-catenin expression in tumor tissues, an effect that was mitigated in T2821 xenografts when ganetespib was combined with IR treatments. These data highlight the promise of combining ganetespib with IR therapies in the treatment of AC lung tumors.

  10. Expressão citofotométrica do marcador CD-34 no adenocarcinoma de cólon CD-34 cytophotometric expression in colon adenocarcinoma

    Directory of Open Access Journals (Sweden)

    João Batista Monteiro Tajra

    2008-12-01

    and CD-34 is one important marker. OBJECTIVE - To evaluate CD-34 biomarker expression through cytophotometric analysis of colon adenocarcinoma samples; to verify the presence of tumor marker expression in different stages of tumor samples according to Dukes modified classification; to determine eventual difference in CD-34 expression while tumor location is either in right or left colon. METHODS - Nineteen samples were submitted to an immunohistochemical method, using anti-CD-34 monoclonal antibody. Marked slides were analyzed by SAMBA system using Immuno 4 software. Biomarker expression consisted in label index and optical density. The parameters considered under investigation were tumor expression, its intensity, correlations to Dukes' classification and tumor's side. RESULTS - The mean rate of CD-34 expression was 66.54, and optical density 43.60. Regarding Dukes' classification, 12 samples B-type presented label index 67.95 and optical density 43.21; seven C-type, label index was 64.12 and optical density 44.27. It was not possible to identify any difference related to Dukes' classification. Tumor side reflected significant difference in label index, but not in optical density. Eleven samples on the left presented 72.08 of label index and 46.70 of optical density. Eight right, demonstrated label index of 58.93 and optical density of 39.44. CONCLUSIONS - CD-34 marker presented a low expression as an angiogenesis marker in colon tumors with no difference between Duke's tumors type-B and type-C. The tumor had higher angiogenic activity in the right than in left colon.

  11. Human Adenocarcinoma Cell Line Sensitivity to Essential Oil Phytocomplexes from Pistacia Species: a Multivariate Approach.

    Science.gov (United States)

    Buriani, Alessandro; Fortinguerra, Stefano; Sorrenti, Vincenzo; Dall'Acqua, Stefano; Innocenti, Gabbriella; Montopoli, Monica; Gabbia, Daniela; Carrara, Maria

    2017-08-11

    Principal component analysis (PCA) multivariate analysis was applied to study the cytotoxic activity of essential oils from various species of the Pistacia genus on human tumor cell lines. In particular, the cytotoxic activity of essential oils obtained from P. lentiscus, P. lentiscus var. chia (mastic gum), P. terebinthus, P. vera, and P. integerrima, was screened on three human adenocarcinoma cell lines: MCF-7 (breast), 2008 (ovarian), and LoVo (colon). The results indicate that all the Pistacia phytocomplexes, with the exception of mastic gum oil, induce cytotoxic effects on one or more of the three cell lines. PCA highlighted the presence of different cooperating clusters of bioactive molecules. Cluster variability among species, and even within the same species, could explain some of the differences seen among samples suggesting the presence of both common and species-specific mechanisms. Single molecules from one of the most significant clusters were tested, but only bornyl-acetate presented cytotoxic activity, although at much higher concentrations (IC50 = 138.5 µg/mL) than those present in the essential oils, indicating that understanding of the full biological effect requires a holistic vision of the phytocomplexes with all its constituents.

  12. IMP3 Predicts Invasion and Prognosis in Human Lung Adenocarcinoma.

    Science.gov (United States)

    Yan, Jinhai; Wei, Qingzhu; Jian, Wenjing; Qiu, Bo; Wen, Jing; Liu, Jianghuan; Fu, Bo; Zhou, Xinhua; Zhao, Tong

    2016-02-01

    Insulin-like growth factor II mRNA-binding protein 3 (IMP3) is an oncofetal protein associated with several aggressive and advanced cancers. Whether IMP3 can predict invasion, and prognosis in patients with human lung adenocarcinoma (LAC) remains unclear. Ninety-five LAC and 75 non-tumor lung tissue samples were included in a tissue microarray. IMP3 expression was assessed by immunohistochemical examination. Correlation between IMP3 expression levels, clinicopathological characteristics, and overall prognosis was evaluated. In a separate in vitro study, RNA interference method was applied for knockdown of IMP3 gene in human LAC cell lines. Invasive potential of LAC cells was then evaluated by transwell migration assay. IMP3 immunoreactivity was observed in 39 out of 95 (41.1 %) LAC patients, but not in non-tumor lung tissues. IMP3 expression levels were closely associated with histological grade (P = 0.037), TNM stage (P = 0.034), and lymph node metastasis (P = 0.011). Patients presenting with positive IMP3 expression (P = 0.000), an advanced TNM stage (P = 0.000), and lymph node metastasis (P = 0.001) had a worse overall survival, compared to those lacking these characteristics. Both IMP3 expression (hazard ratio [HR], 2.310; 95 % confidence interval [CI] 1.192-4.476; P = 0.013) and TNM stage (HR 2.338; 95 % CI 1.393-3.925; P = 0.001) were independent predictors of poor prognosis. The invasive potential of LAC cells was significantly inhibited by IMP3 knockdown. IMP3 appears to play an important role in tumor invasion in patients with LAC and may serve as a useful prognostic biomarker in these patients.

  13. Autofluorescence of normal and tumor mucosa of human colon: a comprehensive analysis

    Science.gov (United States)

    Bottiroli, Giovanni F.; Marchesini, Renato; Croce, Anna C.; Dal Fante, Marco; Cuzzoni, Carolina; Di Palma, Silvana; Spinelli, Pasquale

    1993-08-01

    Both 'in vivo' and 'ex vivo' spectrofluorometric studies of neoplastic and non-neoplastic mucosa of human colon have been carried out, in order to verify the potentials of tissue natural fluorescence as a possible parameter to distinguish normal from diseased tissues, Spectrofluorometric analysis performed at colonoscopy on patients affected by neoplasia, showed that adenocarcinoma, adenoma and non-neoplastic mucosa differ in the fluorescence emissions. The results have been interpreted according to the data obtained on cryostatic sections from biopsies by means of a microspectrofluorometric analysis carried out on each histological component.

  14. Negligible colon cancer risk from food-borne acrylamide exposure in male F344 rats and nude (nu/nu mice-bearing human colon tumor xenografts.

    Directory of Open Access Journals (Sweden)

    Jayadev Raju

    Full Text Available Acrylamide, a possible human carcinogen, is formed in certain carbohydrate-rich foods processed at high temperature. We evaluated if dietary acrylamide, at doses (0.5, 1.0 or 2.0 mg/kg diet reflecting upper levels found in human foods, modulated colon tumorigenesis in two rodent models. Male F344 rats were randomized to receive diets without (control or with acrylamide. 2-weeks later, rats in each group received two weekly subcutaneous injections of either azoxymethane (AOM or saline, and were killed 20 weeks post-injections; colons were assessed for tumors. Male athymic nude (nu/nu mice bearing HT-29 human colon adenocarcinoma cells-derived tumor xenografts received diets without (control or with acrylamide; tumor growth was monitored and mice were killed 4 weeks later. In the F344 rat study, no tumors were found in the colons of the saline-injected rats. However, the colon tumor incidence was 54.2% and 66.7% in the control and the 2 mg/kg acrylamide-treated AOM-injected groups, respectively. While tumor multiplicity was similar across all diet groups, tumor size and burden were higher in the 2 mg/kg acrylamide group compared to the AOM control. These results suggest that acrylamide by itself is not a "complete carcinogen", but acts as a "co-carcinogen" by exacerbating the effects of AOM. The nude mouse study indicated no differences in the growth of human colon tumor xenografts between acrylamide-treated and control mice, suggesting that acrylamide does not aid in the progression of established tumors. Hence, food-borne acrylamide at levels comparable to those found in human foods is neither an independent carcinogen nor a tumor promoter in the colon. However, our results characterize a potential hazard of acrylamide as a colon co-carcinogen in association with known and possibly other environmental tumor initiators/promoters.

  15. Negligible Colon Cancer Risk from Food-Borne Acrylamide Exposure in Male F344 Rats and Nude (nu/nu) Mice-Bearing Human Colon Tumor Xenografts

    Science.gov (United States)

    Raju, Jayadev; Roberts, Jennifer; Sondagar, Chandni; Kapal, Kamla; Aziz, Syed A.; Caldwell, Don; Mehta, Rekha

    2013-01-01

    Acrylamide, a possible human carcinogen, is formed in certain carbohydrate-rich foods processed at high temperature. We evaluated if dietary acrylamide, at doses (0.5, 1.0 or 2.0 mg/kg diet) reflecting upper levels found in human foods, modulated colon tumorigenesis in two rodent models. Male F344 rats were randomized to receive diets without (control) or with acrylamide. 2-weeks later, rats in each group received two weekly subcutaneous injections of either azoxymethane (AOM) or saline, and were killed 20 weeks post-injections; colons were assessed for tumors. Male athymic nude (nu/nu) mice bearing HT-29 human colon adenocarcinoma cells-derived tumor xenografts received diets without (control) or with acrylamide; tumor growth was monitored and mice were killed 4 weeks later. In the F344 rat study, no tumors were found in the colons of the saline-injected rats. However, the colon tumor incidence was 54.2% and 66.7% in the control and the 2 mg/kg acrylamide-treated AOM-injected groups, respectively. While tumor multiplicity was similar across all diet groups, tumor size and burden were higher in the 2 mg/kg acrylamide group compared to the AOM control. These results suggest that acrylamide by itself is not a “complete carcinogen”, but acts as a “co-carcinogen” by exacerbating the effects of AOM. The nude mouse study indicated no differences in the growth of human colon tumor xenografts between acrylamide-treated and control mice, suggesting that acrylamide does not aid in the progression of established tumors. Hence, food-borne acrylamide at levels comparable to those found in human foods is neither an independent carcinogen nor a tumor promoter in the colon. However, our results characterize a potential hazard of acrylamide as a colon co-carcinogen in association with known and possibly other environmental tumor initiators/promoters. PMID:24040114

  16. Oropharyngeal perinatal colonization by human papillomavirus.

    Science.gov (United States)

    Sánchez-Torices, María Soledad; Corrales-Millan, Rocío; Hijona-Elosegui, Jesús J

    2016-01-01

    Human papillomavirus (HPV) infection is the most common human sexually transmitted disease. It is clinically relevant because this condition is necessary for the development of epithelial cervical cancer, and it is also a factor closely associated with the occurrence of diverse tumours and various benign and malignant lesions of the head and neck area. The infective mechanism in most of these cases is associated with sexual intercourse, but there is recent scientific evidence suggesting that HPV infection may also be acquired by other routes of infection not necessarily linked to sexual contact. One of them is vertical transmission from mother to child, either during pregnancy or at the time of delivery. The aim of our research was to study maternal-foetal HPV transmission during childbirth in detail, establishing the rate of oropharyngeal neonatal HPV in vaginal deliveries. The presence and type of HPV viral DNA at the time of delivery in samples of maternal cervical secretions, amniotic fluid, venous cord blood samples and neonatal oropharynx in pregnant women (and their babies) were determined. The rate of oropharyngeal neonatal HPV colonization in vaginal deliveries was 58.24%. The maternal and neonatal HPV colonization mechanism is essentially, but not exclusively, transvaginal. Copyright © 2014 Elsevier España, S.L.U. y Sociedad Española de Otorrinolaringología y Cirugía de Cabeza y Cuello. All rights reserved.

  17. MicroRNA-1254 inhibits the migration of colon adenocarcinoma cells by targeting PSMD10.

    Science.gov (United States)

    Chu, Yi Min; Peng, Hai Xia; Xu, Ying; Yang, Da Ming; Zhou, Feng Li; Li, Ji; Kuai, Rong; Lin, Yong

    2017-03-01

    MicroRNA-1254 (miR-1254) has not been studied in colorectal cancer (CRC) to date. This study aimed to investigate the inhibitory mechanism of miR-1254 in CRC tumorigenesis. MiR-1254 expression was examined using real-time polymerase chain reaction in CRC and adjacent non-tumorous tissues. The correlation between miR-1254 expressions and proliferation and migration of cancer cells was determined using the CCK-8 and transwell assays. RNA sequencing was used to identify differentially expressed genes downstream from miR-1254. A luciferase reporter assay was used to confirm the direct interaction between miR-1254 and its predicted target gene, PSMD10. Moreover, PSMD10 was either overexpressed or silenced in colon carcinoma cells overexpressing miR-1254 to determine whether their interaction contributed to CRC migration and epithelial-mesenchymal transition (EMT). Significantly lower miR-1254 expressions were observed in CRC tissues than in adjacent non-tumorous tissues. Exogenous miR-1254 expression suppressed the migration of colon carcinoma cell lines SW1116 and HCT116. RNA sequencing and luciferase assays revealed that miR-1254 directly binded to the 3'-untranslated region of PSMD10, an important regulator of EMT and cell migration. PSMD10 knockdown inhibited EMT and colon cancer cell migration, whereas PSMD10 overexpression reversed the inhibition of EMT and cell migration caused by miR-1254. MiR-1254 may act as a tumor suppressor in CRC and may inhibit CRC migration by directly targeting PSMD10 to suppress the EMT process. © 2017 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.

  18. Metastatic adenocarcinoma in a thyroid colloid nodule: a rare presentation of colon cancer.

    Science.gov (United States)

    Osin, P; Shiloni, E; Pikarsky, A J; Okon, E

    1996-08-01

    Colorectal cancer can remain asymptomatic for years. Frequently symptoms develop insidiously and may often remain unnoticed for long periods, even in the presence of disseminated disease. We herein report an unusual case of a patient with carcinoma of the sigmoid colon and multiple liver metastases. The diagnosis was established only after the patient was operated on for a large colloid nodule, a single microscopic metastatic focus being noticed in the histologic sections. The differential diagnosis compared with the columnar type of papillary carcinoma is discussed.

  19. Identification of differentially expressed genes in normal mucosa, adenoma and adenocarcinoma of colon by SSH.

    Science.gov (United States)

    Luo, M J; Lai, M D

    2001-10-01

    To construct subtracted cDNA libraries and further identify differentially expressed genes that are related to the development of colorectal carcinoma(CRC). Suppression subtractive hybridization(SSH) was done on cDNAs of normal mucosa, adenoma and adenocarcinoma tissues from the same patient. Three subtracted cDNA libraries were constructed and then hybridized with forward and backward subtracted probes for differential screening. Positive clones from each subtracted cDNA library were selected for sequencing and BLAST analysis. Finally, virtual Northern Blot confirmed such differential expression. By this way, there were about 3-4 X 10(2) clones identified in each subtracted cDNA library, in which about 85% positive clones were differentially screened. Sequencing and BLAST homology search revealed some clones containing sequences of known gene fragments and several possibly novel genes showing few or no sequence homologies with any known sequences in the database. All results confirmed the effectiveness and sensitivity of SSH. The differentially expressed genes during the development of CRC can be used to shed light on the pathogenesis of CRC and be useful genetic markers for early diagnosis and therapy.

  20. Expression of Fas ligand by human gastric adenocarcinomas: a potential mechanism of immune escape in stomach cancer.

    LENUS (Irish Health Repository)

    Bennett, M W

    2012-02-03

    BACKGROUND: Despite being immunogenic, gastric cancers overcome antitumour immune responses by mechanisms that have yet to be fully elucidated. Fas ligand (FasL) is a molecule that induces Fas receptor mediated apoptosis of activated immunocytes, thereby mediating normal immune downregulatory roles including immune response termination, tolerance acquisition, and immune privilege. Colon cancer cell lines have previously been shown to express FasL and kill lymphoid cells by Fas mediated apoptosis in vitro. Many diverse tumours have since been found to express FasL suggesting that a "Fas counterattack" against antitumour immune effector cells may contribute to tumour immune escape. AIM: To ascertain if human gastric tumours express FasL in vivo, as a potential mediator of immune escape in stomach cancer. SPECIMENS: Thirty paraffin wax embedded human gastric adenocarcinomas. METHODS: FasL protein was detected in gastric tumours using immunohistochemistry; FasL mRNA was detected in the tumours using in situ hybridisation. Cell death was detected in situ in tumour infiltrating lymphocytes using terminal deoxynucleotidyl transferase mediated dUTP nick end labelling (TUNEL). RESULTS: Prevalent expression of FasL was detected in all 30 resected gastric adenocarcinomas examined. In the tumours, FasL protein and mRNA were co-localised to neoplastic gastric epithelial cells, confirming expression by the tumour cells. FasL expression was independent of tumour stage, suggesting that it may be expressed throughout gastric cancer progression. TUNEL staining disclosed a high level of cell death among lymphocytes infiltrating FasL positive areas of tumour. CONCLUSIONS: Human gastric adenocarcinomas express the immune downregulatory molecule, FasL. The results suggest that FasL is a prevalent mediator of immune privilege in stomach cancer.

  1. The role of the obestatin/GPR39 system in human gastric adenocarcinomas.

    Science.gov (United States)

    Alén, Begoña O; Leal-López, Saúl; Alén, María Otero; Viaño, Patricia; García-Castro, Victoria; Mosteiro, Carlos S; Beiras, Andrés; Casanueva, Felipe F; Gallego, Rosalía; García-Caballero, Tomás; Camiña, Jesús P; Pazos, Yolanda

    2016-02-02

    Obestatin, a 23-amino acid peptide encoded by the ghrelin gene, and the GPR39 receptor were reported to be involved in the control of mitogenesis of gastric cancer cell lines; however, the relationship between the obestatin/GPR39 system and gastric cancer progression remains unknown. In the present study, we determined the expression levels of the obestatin/GPR39 system in human gastric adenocarcinomas and explored their potential functional roles. Twenty-eight patients with gastric adenocarcinomas were retrospectively studied, and clinical data were obtained. The role of obestatin/GPR39 in gastric cancer progression was studied in vitro using the human gastric adenocarcinoma AGS cell line. Obestatin exogenous administration in these GPR39-bearing cells deregulated the expression of several hallmarks of the epithelial-mesenchymal transition (EMT) and angiogenesis. Moreover, obestatin signaling promoted phenotypic changes via GPR39, increasingly impacting on the cell morphology, proliferation, migration and invasion of these cells. In healthy human stomachs, obestatin expression was observed in the neuroendocrine cells and GPR39 expression was localized mainly in the chief cells of the oxyntic glands. In human gastric adenocarcinomas, no obestatin expression was found; however, an aberrant pattern of GPR39 expression was discovered, correlating to the dedifferentiation of the tumor. Altogether, our data strongly suggest the involvement of the obestatin/GPR39 system in the pathogenesis and/or clinical outcome of human gastric adenocarcinomas and highlight the potential usefulness of GPR39 as a prognostic marker in gastric cancer.

  2. Characterization and properties of nine human ovarian adenocarcinoma cell lines.

    Science.gov (United States)

    Langdon, S P; Lawrie, S S; Hay, F G; Hawkes, M M; McDonald, A; Hayward, I P; Schol, D J; Hilgers, J; Leonard, R C; Smyth, J F

    1988-11-01

    Four series of cell lines have been derived from patients with ovarian adenocarcinoma. Nine cell lines have been established at one from a solid metastasis. Six lines were derived from the ascites or pleural effusion of patients with poorly differentiated adenocarcinoma: PEO1, PEO4, and PEO6 from one patient, PEA1 and PEA2 from a second, and PEO16 from a third. Three lines (PEO14 and PEO23 from ascites and TO14 from a solid metastasis) were derived from a patient with a well-differentiated serous adenocarcinoma. Each set of cell lines was morphologically distinct. The five cell lines PEO1, PEO4, PEO6, PEA1, and PEA2 had cloning efficiencies on plastic of 1-2% and only a few cells in these lines expressed alkaline phosphatase or vimentin. Only a low percentage of these cells reacted with the monoclonal antibodies 123C3 and 123A8 but most reacted with OC125. Conversely the cell lines PEO14, TO14, PEO23, and PEO16 were characterized by low cloning efficiency values (less than 0.05%), marked expression of alkaline phosphatase and vimentin, and good reaction with 123C3 and 123A8 but not OC125. These four cell lines also exhibited dome formation. Four of the cell lines, PEO1, PEO4, PEO6, and PEO16, have been xenografted into immune-deprived mice and found to be tumorigenic.

  3. Human wound colonization by Lucilia eximia and Chrysomya rufifacies (Diptera: Calliphoridae): myiasis, perimortem, or postmortem colonization?

    Science.gov (United States)

    Sanford, Michelle R; Whitworth, Terry L; Phatak, Darshan R

    2014-05-01

    The infestation of human or animal tissues by fly larvae has been given distinctive terminology depending on the timing and location of colonization. Wounds and orifices colonized by Diptera in a living human or animal are typically referred to as myiasis. When the colonization occurs after death, it is referred to as postmortem colonization and can be used to estimate the minimum postmortem interval. What happens when the human, as in the case presented here, has a necrotic limb while the human remains alive, at least for a short period of time? The case presented here documents perimortem wound colonization by Lucilia eximia (Wiedemann) and Chrysomya rufifacies (Macquart) and the considerations for approximating development temperatures and estimating the time of colonization (TOC). This represents the first record of L. eximia in human myiasis in the United States and the first record of the co-occurrence of L. eximia and C. rufifacies in human myiasis in the United States. The TOC was estimated using both ambient and body temperature. Insect colonization before death complicates the estimation of TOC and minimum postmortem interval and illustrates the problem of temperature approximation in forensic entomology casework.

  4. Binding of chemical carcinogens to macromolecules in cultured human colon

    DEFF Research Database (Denmark)

    Autrup, Herman; Harris, C.C.; Stoner, G.D.

    1977-01-01

    Metabolic activation of different chemical classes of carcinogens was studied in cultured human colon epithelia. Human colon epithelia were maintained in explant culture up to 4 days. Binding of benzo(a)pyrene, dimethylnitrosamine, and 1,2- dimethylhydrazine was found in both cell DNA and protein...

  5. Nuclear expression of claudin-3 in human colorectal adenocarcinoma cell lines and tissues.

    Science.gov (United States)

    Tokuhara, Yasunori; Morinishi, Tatsuya; Matsunaga, Toru; Sakai, Manabu; Sakai, Takayoshi; Ohsaki, Hiroyuki; Kadota, Kyuichi; Kushida, Yoshio; Haba, Reiji; Hirakawa, Eiichiro

    2018-01-01

    Claudins are members of a large family of transmembrane proteins, which are essential for the formation of tight junctions and have a significant effect on the biological behavior of tumor progression. Previous studies have demonstrated that several claudins show aberrant expression patterns in numerous types of cancer. The present study investigated the expression and localization of claudin-3 and claudin-7 in human colorectal adenocarcinoma cell lines and tissues. The protein expression levels of claudin-3 and claudin-7 were determined using immunocytochemical and immunohistochemical staining. Claudin-3, but not claudin-7, exhibited nuclear localization in the human colorectal adenocarcinoma Caco-2 and SW620 cell lines. Surgically resected colorectal adenocarcinoma tissue specimens were obtained, and the associations between the expression of claudin-3 or claudin-7 and various clinicopathological parameters were analyzed. The membranous expression rates of claudin-3 and claudin-7 were 58.0 and 50.0%, while their nuclear expression rates were 22.0 and 2.0%, respectively. The membranous expression of claudin-3 and claudin-7 was not associated with any clinicopathological factors, whereas the nuclear expression of claudin-3 was associated with histological type and was significantly increased in colorectal mucinous adenocarcinomas compared with that in well- to moderately-differentiated colorectal adenocarcinomas (P<0.01). However, no associations were observed between the nuclear expression of claudin-7 and any clinicopathological parameter. In conclusion, the nuclear expression of claudin-3 in colorectal mucinous adenocarcinoma may be involved in the biological transformation of tumors. The results from the present study indicated that claudin-3 is an important protein associated with histological type and has potential as a prognostic marker. Although the mechanisms underlying the nuclear localization of claudin-3 in tumorigenesis have not yet been elucidated in

  6. Tetrac-conjugated polymersomes for integrin-targeted delivery of camptothecin to colon adenocarcinoma in vitro and in vivo.

    Science.gov (United States)

    Alibolandi, Mona; Rezvani, Rouhollah; Farzad, Sara Amel; Taghdisi, Seyed Mohammad; Abnous, Khalil; Ramezani, Mohammad

    2017-10-30

    In this study, we prepared tetraiodothyroacetic acid (tetrac) conjugated PEG-PLGA polymersomes for the targeted delivery of camptothecin to colon adenocarcinoma. Tetrac, which binds to integrin αvβ3 with high affinity and specificity, was covalently conjugated to the surface of the PEGylated polymersomal formulation of camptothecin (CPT). The hydrodynamic and morphological properties of the prepared system were evaluated using TEM (transmission electron microscopy), SEM (scanning electron microscopy) and DLS (dynamic light scattering) experiments. Camptothecin was encapsulated in the polymersomal system with encapsulation efficiency and loading content of 84±10.12 and 4.2±0.82, respectively. The in vitro release profile of camptothecin from the polymersomal formulation revealed the sustained release pattern. In vitro cytotoxicity experiments confirmed that the tetrac-conjugated camptothecin loaded-polymersomes had higher cellular toxicity towards integrin-overexpressed HT29 and C26 colorectal cancer cells than integrin-negative CHO cell line. The in vivo tumor inhibitory effect of tetrac-conjugated camptothecin loaded-polymersomes demonstrated an enhanced therapeutic index of integrin targeted polymersomal formulation over both non-targeted polymersomal formulation and free camptothecin in C26 tumor bearing mice. The obtained results demonstrated that the prepared tetrac-conjugated polymersomes were able to control the release of camptothecin, and significantly increase the therapeutic index of compthotecin. This study demonstrates the versatility of integrin-targeted tetrac-conjugated PEG-PLGA polymersomal formulation as an anti-cancer nano-pharmaceutical platform. Copyright © 2017 Elsevier B.V. All rights reserved.

  7. ERK/pERK expression and B-raf mutations in colon adenocarcinomas: correlation with clinicopathological characteristics

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    Levidou Georgia

    2012-02-01

    Full Text Available Abstract Background Colorectal (CRC carcinogenesis through various morphological stages has been linked to several genetic and epigenetic changes. The Raf/MEK/ERK (MAPK signal transduction cascade is an important mediator of a number of cellular fates. Methods In this study, we investigated the presence of B-raf and K-ras mutations in 94 consecutive cases of primary colon adenocarcinoma in correlation with the immunohistochemical expression of total and activated ERK and the expression of mismatch repair proteins (MMR hMLH1 and hMSH2 as well as their correlations with standard clinicopathological parameters. Results The immunostaining pattern for total and activated ERK was nuclear and cytoplasmic. hMLH1 and hMSH2 proteins were preserved in 45/63 (71.43% cases and 35/53 (66.04% cases respectively. Total ERK nuclear expression, was positively correlated with tumor stage (p = 0.049, whereas nuclear pERK expression was positively correlated with histological grade (p = 0.0113 and tumor stage (p = 0.0952, although the latter relationship was of marginal significance. DNA sequencing showed that 12 samples (12.7% had a mutation in B-RAF Exon 15 and none in Exon 11, whereas 22 (23.4% had a K-ras mutation. Disruption of the MAP kinase pathway-either through K-ras or B-raf mutation-was detected in 37% of all the examined cases, although the overexpression of total and activated ERK1/2 was not correlated with the mutational status of K-ras or B-raf genes. Finally, the preservation of hMLH1 or hMSH2 immunoexpression was not correlated with the presence of B-raf and/or K-ras mutations. Conclusions In this study, we present evidence that ERK activation occurs in a K-ras or B-raf -independent manner in the majority of primary colon cancer cases. Moreover, B-raf mutations are not associated with mismatch-repair deficiency through loss of hMLH1 or hMSH2 expression. Activated ERK could possibly be implicated in tumor invasiveness as well as in the acquisition of

  8. β-Catenin activation in fundic gland polyps, gastric cancer and colonic polyps in families afflicted by 'gastric adenocarcinoma and proximal polyposis of the stomach' (GAPPS).

    Science.gov (United States)

    McDuffie, Lucas A; Sabesan, Arvind; Allgäeuer, Michael; Xin, Liqiang; Koh, Christopher; Heller, Theo; Davis, Jeremy L; Raffeld, Mark; Miettienen, Markku; Quezado, Martha; Rudloff, Udo

    2016-09-01

    To evaluate possible colon involvement in the 'gastric adenocarcinoma and proximal polyposis of the stomach' (GAPPS) gastrointestinal polyposis syndrome. Prospective clinicopathological evaluation of two GAPPS families and expression of nuclear β-catenin, p53 and Ki67 measured by immunohistochemistry on endoscopic and surgical specimens from patients with GAPPS. Patients with the GAPPS phenotype were more frequently affected by colonic polyps than patients at risk within the same families (pgastric cancers including increased expression of nuclear β-catenin, Ki67 and p53. Both gastric and colonic lesions harboured activating somatic variants of β-catenin signalling. Similarities in expression markers in fundic gland and colonic polyps, together with an enrichment of colonic adenomas in family members affected by GAPPS phenotype compared with family members at risk, support mild colonic involvement of this rare cancer syndrome. Colonoscopic screening might be warranted. #09-C-0079; Results. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  9. Microbiota source impact in vitro metabolite colonic production and anti-proliferative effect of spent coffee grounds on human colon cancer cells (HT-29).

    Science.gov (United States)

    Hernández-Arriaga, Angélica María; Dave Oomah, B; Campos-Vega, Rocio

    2017-07-01

    Human gut flora-mediated non-digestible fraction of spent coffee grounds (hgf-NDSCG) was evaluated for its chemopreventive effect and molecular mechanisms involved on human colon adenocarcinoma HT-29 cell survival using two different microbiota source [lean (L) and overweight (OW)]. The source of human gut flora (hgf) (L or OW) affected the pH of hgf-NDSCG only minimally, but linearly reduced those of hgf-inulin. The variability between lean and overweight microbiota was characterized by the metabolism and/or bioaccessibility of different phenolic metabolites, their intermediate and end products as well as by variable time courses. Apoptosis of colon cancer HT-29 cells depended on the microbiota source with the lean microbiota expressing a low lethal concentration 50 (LC50/L-hgf-NDSCG=13.5%). We demonstrate that NDSCG and its colonic metabolite from lean microbiota induced HT-29 cell apoptosis by reducing catalase and 8-iso-prostaglandin F2α as biomarkers of in vivo oxidative stress as the primary mechanism underlying its overall chemoprotection against colon cancer. Copyright © 2017 Elsevier Ltd. All rights reserved.

  10. Evaluating the effect of four extracts of avocado fruit on esophageal squamous carcinoma and colon adenocarcinoma cell lines in comparison with peripheral blood mononuclear cells.

    Science.gov (United States)

    Vahedi Larijani, Laleh; Ghasemi, Maryam; AbedianKenari, Saeid; Naghshvar, Farshad

    2014-01-01

    Most patients with gastrointestinal cancers refer to the health centers at advanced stages of the disease and conventional treatments are not significantly effective for these patients. Therefore, using modern therapeutic approaches with lower toxicity bring higher chance for successful treatment and reduced adverse effects in such patients. The aim of this study is to evaluate the effect of avocado fruit extracts on inhibition of the growth of cancer cells in comparison with normal cells. In an experimental study, ethanol, chloroform, ethyl acetate, and petroleum extracts of avocado (Persea americana) fruit were prepared. Then, the effects if the extracts on the growth of esophageal squamous cell carcinoma and colon adenocarcinoma cell lines were evaluated in comparison with the control group using the MTT test in the cell culture medium. Effects of the four extracts of avocado fruit on three cells lines of peripheral blood mononuclear cells, esophageal squamous cell carcinoma, and colon adenocarcinoma were tested. The results showed that avocado fruit extract is effective in inhibition of cancer cell growth in comparison with normal cells (PAvocado fruit is rich in phytochemicals, which play an important role in inhibition of growth of cancer cells. The current study for the first time demonstrates the anti-cancer effect of avocado fruit extracts on two cancers common in Iran. Therefore, it is suggested that the fruit extracts can be considered as appropriate complementary treatments in treatment of esophageal and colon cancers.

  11. Human Papillomavirus in Endometrial Adenocarcinomas: Infectious Agent or a Mere “Passenger”?

    Science.gov (United States)

    Giatromanolaki, A.; Sivridis, E.; Papazoglou, D.; Koukourakis, M. I.; Maltezos, E.

    2007-01-01

    Aims. To investigate the possible association of human papillomavirus (HPV) with endometrial hyperplasias and neoplasia. Does HPV play any role in the initiation or prognosis of endometrial adenocarcinomas? Methods. Twenty-five endometrial adenocarcinomas of the endometrioid cell type, with and without squamous differentiation, and twenty-four endometrial hyperplasias of various forms (simple, complex, and atypical) were analyzed for the presence of type 16 and 18 HPV by the polymerase chain reaction (PCR). The results were related to histopathological features of the tumour, and the patients' age, and prognosis. Results. Six of 25 endometrial adenocarcinomas were HPV 16-positive (24%), and 5 of 25 (20%) were HPV 18-positive. Simple endometrial hyperplasias was associated somewhat more commonly with HPV 16 and 18 (2/8 and 1/8 cases, resp.) than hyperplasias progressing to endometrial adenocarcinomas, namely, atypical endometrial hyperplasia (1/8 and 0/8 cases, resp.). None of the positive cases in the series, whether hyperplastic or neoplastic, demonstrated cytological evidence of HPV infection. There was no relation between HPV-positive cases and squamous differentiation, depth of myometrial invasion, lymphatic involvement, lymphocytic response, patients' age, or prognosis. Conclusion. It appears that the presence of HPV in the endometrium, as detected by PCR, does not play any role in the initiation or prognosis of endometrial adenocarcinoma. PMID:18274613

  12. Colonic Fermentation: A Neglected Topic in Human Physiology Education

    Science.gov (United States)

    Valeur, Jorgen; Berstad, Arnold

    2010-01-01

    Human physiology textbooks tend to limit their discussion of colonic functions to those of absorbing water and electrolytes and storing waste material. However, the colon is a highly active metabolic organ, containing an exceedingly complex society of microbes. By means of fermentation, gastrointestinal microbes break down nutrients that cannot be…

  13. Verification of microRNA expression in human endometrial adenocarcinoma.

    Science.gov (United States)

    Jurcevic, Sanja; Klinga-Levan, Karin; Olsson, Björn; Ejeskär, Katarina

    2016-04-02

    MicroRNAs are small non-coding RNAs that have been implicated in tumor initiation and progression. In a previous study we identified 138 miRNAs as differentially expressed in endometrial adenocarcinoma compared to normal tissues. One of these miRNAs was miRNA-34a, which regulates several genes involved in the Notch pathway, which is frequently altered in endometrial cancer. The aims of this study were to verify the differential expression of a subset of miRNAs and to scrutinize the regulatory role of mir-34a on the target genes NOTCH1 and DLL1. Twenty-five miRNAs that were previously identified as differentially expressed were subjected to further analysis using qPCR. To investigate the regulation of NOTCH1 and DLL1 by mir-34a, we designed gain- and loss-of-function experiments in Ishikawa and HEK293 cell lines by transfection with a synthetic mir-34a mimic and a mir-34a inhibitor. Of the 25 validated miRNAs, seven were down-regulated and 18 were up-regulated compared to normal endometrium, which was fully consistent with our previous findings. In addition, the up-regulation of mir-34a led to a significant decrease in mRNA levels of NOTCH1 and DLL1, while down-regulation led to a significant increase in mRNA levels of these two genes. We verified both up-regulated and down-regulated miRNAs in the tumor samples, indicating various roles of microRNAs during tumor development. Mir-34a functions as a regulator by decreasing the expression of NOTCH1 and DLL1. Our study is the first to identify a correlation between mir-34a and its target genes NOTCH1 and DLL1 in endometrial adenocarcinoma.

  14. Antiproliferative effects on colon adenocarcinoma cells induced by co-administration of vitamin K1 and Lactobacillus rhamnosus GG.

    Science.gov (United States)

    Orlando, Antonella; Linsalata, Michele; Russo, Francesco

    2016-06-01

    Vitamin K (VK), an essential nutrient associated with the clotting cascade, has also been demonstrated to have anticancer properties in various cancer cells including colon cancer cells. Also probiotics have gained interest as potential anticancer agents. Among them, Lactobacillus rhamnosus GG (L.GG) has been shown to inhibit cell proliferation and polyamine biosynthesis as well as to induce apoptosis in different human gastrointestinal cancer cells. Nevertheless, the exact mechanisms involved in these actions are not completely elucidated. Therefore, the aims of the present study were to evaluate in three differently graded human colon cancer cells (namely Caco-2, HT-29 and SW480) the effects of increasing VK1 concentrations, administered alone or in combination with viable L.GG, on the cell proliferation evaluated by MTT test, apoptosis investigated by Bax/Bcl-2 ratio and the percentage of the apoptotic cells, and the cell cycle evaluated by MUSE cell analyzer. Both VK1 and L.GG administered alone up to 72 h, caused inhibition of proliferation, induction of apoptosis and the cell cycle arrest in all the tested colon cancer cells. When VK1 and L.GG were co-administered, the addition of increasing VK1 concentrations potentiated the probiotic antiproliferative effect in a dose-dependent manner, being also related to the individual features of each cell line. The effect was more evident in Caco-2 and HT-29 cells compared to the less differentiated SW480. The enhanced antiproliferative efficacy due to co-administration of L.GG and VK1 could represent a suitable option in a functional food strategy for cancer growth inhibition and chemoprevention.

  15. Newly Diagnosed Colonic Adenocarcinoma: The Presenting Sign in a Young Woman with Undiagnosed Crohn’s Disease in the Absence of Primary Sclerosing Cholangitis and a Normal Microsatellite Instability Profile

    Directory of Open Access Journals (Sweden)

    Brett Matthew Lowenthal

    2017-01-01

    Full Text Available Ulcerative colitis has long been linked with an increased risk for colonic adenocarcinoma, whereas Crohn’s disease (CD has recently been reported to pose a similar increased risk. We report a 33-year-old healthy female with no family history who presented with abdominal pain and a colon mass. Histopathology revealed a moderately differentiated adenocarcinoma extending through the muscularis propria with metastatic lymph nodes and intact mismatch repair proteins by immunohistochemical expression and gene sequencing. The nonneoplastic grossly uninvolved background mucosa showed marked crypt distortion, crypt abscesses, CD-like lymphoid hyperplasia, transmural inflammation, and reactive epithelial atypia. Additional patient questioning revealed frequent loose stools since she was a teenager leading to diagnosis of a previously undiagnosed CD without primary sclerosing cholangitis (PSC. The adenocarcinoma is suspected to be related to the underlying CD. Newly diagnosed adenocarcinoma in a young female as the presenting sign for CD in the absence of PSC is extremely rare.

  16. Genetic mutation analysis of human gastric adenocarcinomas using ion torrent sequencing platform.

    Directory of Open Access Journals (Sweden)

    Zhi Xu

    Full Text Available Gastric cancer is the one of the major causes of cancer-related death, especially in Asia. Gastric adenocarcinoma, the most common type of gastric cancer, is heterogeneous and its incidence and cause varies widely with geographical regions, gender, ethnicity, and diet. Since unique mutations have been observed in individual human cancer samples, identification and characterization of the molecular alterations underlying individual gastric adenocarcinomas is a critical step for developing more effective, personalized therapies. Until recently, identifying genetic mutations on an individual basis by DNA sequencing remained a daunting task. Recent advances in new next-generation DNA sequencing technologies, such as the semiconductor-based Ion Torrent sequencing platform, makes DNA sequencing cheaper, faster, and more reliable. In this study, we aim to identify genetic mutations in the genes which are targeted by drugs in clinical use or are under development in individual human gastric adenocarcinoma samples using Ion Torrent sequencing. We sequenced 737 loci from 45 cancer-related genes in 238 human gastric adenocarcinoma samples using the Ion Torrent Ampliseq Cancer Panel. The sequencing analysis revealed a high occurrence of mutations along the TP53 locus (9.7% in our sample set. Thus, this study indicates the utility of a cost and time efficient tool such as Ion Torrent sequencing to screen cancer mutations for the development of personalized cancer therapy.

  17. Genetic mutation analysis of human gastric adenocarcinomas using ion torrent sequencing platform.

    Science.gov (United States)

    Xu, Zhi; Huo, Xinying; Ye, Hua; Tang, Chuanning; Nandakumar, Vijayalakshmi; Lou, Feng; Zhang, Dandan; Dong, Haichao; Sun, Hong; Jiang, Shouwen; Zhang, Guangchun; Liu, Zhiyuan; Dong, Zhishou; Guo, Baishuai; He, Yan; Yan, Chaowei; Wang, Lu; Su, Ziyi; Li, Yangyang; Gu, Dongying; Zhang, Xiaojing; Wu, Xiaomin; Wei, Xiaowei; Hong, Lingzhi; Zhang, Yangmei; Yang, Jinsong; Gong, Yonglin; Tang, Cuiju; Jones, Lindsey; Huang, Xue F; Chen, Si-Yi; Chen, Jinfei

    2014-01-01

    Gastric cancer is the one of the major causes of cancer-related death, especially in Asia. Gastric adenocarcinoma, the most common type of gastric cancer, is heterogeneous and its incidence and cause varies widely with geographical regions, gender, ethnicity, and diet. Since unique mutations have been observed in individual human cancer samples, identification and characterization of the molecular alterations underlying individual gastric adenocarcinomas is a critical step for developing more effective, personalized therapies. Until recently, identifying genetic mutations on an individual basis by DNA sequencing remained a daunting task. Recent advances in new next-generation DNA sequencing technologies, such as the semiconductor-based Ion Torrent sequencing platform, makes DNA sequencing cheaper, faster, and more reliable. In this study, we aim to identify genetic mutations in the genes which are targeted by drugs in clinical use or are under development in individual human gastric adenocarcinoma samples using Ion Torrent sequencing. We sequenced 737 loci from 45 cancer-related genes in 238 human gastric adenocarcinoma samples using the Ion Torrent Ampliseq Cancer Panel. The sequencing analysis revealed a high occurrence of mutations along the TP53 locus (9.7%) in our sample set. Thus, this study indicates the utility of a cost and time efficient tool such as Ion Torrent sequencing to screen cancer mutations for the development of personalized cancer therapy.

  18. Echoendoscopic characterization of the human colon

    Directory of Open Access Journals (Sweden)

    Fernando M. Castro-Poças

    Full Text Available Purpose: To characterize colon and rectum walls, pericolic and perirectal spaces, using endoscopic ultrasonography miniprobes. Methods: Sixty individuals (50% males, aged 18-80, were included. Using 12 and 20 MHz endoscopic ultrasonography miniprobes, all different colon segments (ascending, transverse, descending, sigmoid and rectum were evaluated according to the number and thickness of the different layers in intestinal wall, to the presence and (largest diameter of vessels in the submucosa and of peri-intestinal nodes. Results: The 20 MHz miniprobe identified a higher number of layers than the 12 MHz miniprobe, with medians of 7 and 5 respectively (p < 0.001. The rectal wall (p = 0.001, its muscularis propria (p < 0.001 and mucosa (p = 0.01 were significantly thicker than the different segments of the colon, which had no significant differences between them. Patients aged 41-60 presented thicker colonic wall and muscularis propria in descending (p = 0.001 and p = 0.004 and rectum (p=0.01 and p=0.01. Submucosal vessels were identified in 30% of individuals in descending and rectum, and in 12% in ascending. Adenopathies were observed in 9% of the colon segments and 5% in rectum. Conclusions: A higher frequency enabled the identification of a higher number of layers. Rectal wall is thicker than the one from all the segments of the colon and there are no differences between these, namely in the ascending colon. Moreover, peri-intestinal adenopathies were rarely identified but present in asymptomatic individuals. All together, these results describe for the first time features which are relevant during staging and therapeutic management of colonic lesions.

  19. Human Colon-Derived Soluble Factors Modulate Gut Microbiota Composition

    OpenAIRE

    Hevia, Arancha; Bernardo, David; Montalvillo, Enrique; Al-Hassi, Hafid O.; Fernández-Salazar, Luis; Garrote, Jose A.; Milani, Christian; Ventura, Marco; Arranz, Eduardo; Knight, Stella C.; Margolles, Abelardo; Sánchez, Borja

    2015-01-01

    The commensal microbiota modulates immunological and metabolic aspects of the intestinal mucosa contributing to development of human gut diseases including inflammatory bowel disease. The host/microbiota interaction often referred to as a crosstalk, mainly focuses on the effect of the microbiota on the host neglecting effects that the host could elicit on the commensals. Colonic microenvironments from three human healthy controls (obtained from the proximal and distal colon, both in resting c...

  20. Factors associated with complete endoscopic resection of an invasive adenocarcinoma in a colorectal adenoma Factores asociados a la resección endoscópica completa del adenocarcinoma invasivo sobre adenoma de colon

    Directory of Open Access Journals (Sweden)

    Paola Quintas

    2012-11-01

    Full Text Available Background and objective: endoscopic polypectomy may allow curative resection of invasive adenocarcinoma on colorectal adenoma. Our goal is was to determine the factors associated with complete endoscopic resection of invasive adenocarcinoma. Methods: retrospective observational study. We included 151 patients with invasive adenocarcinoma on adenomas endoscopically resected between 1999 and 2009. We determined those variables independently related to incomplete resection by a logistic regression. Relation was expressed as Odds Ratio (OR and its 95% confidence interval (95% CI. Results: patients were predominantly male (66.2% and their mean age was 68.03 ± 10.65 years. Colonoscopy was incomplete in 84% of the patients and 60.3% had synchronous adenomas. Invasive adenocarcinoma was mainly located in distal colon (90.7% and morphology was pedunculated in 75.5%. The endoscopic average size was 22.61 ± 10.86 mm. Submucosal injection was required in 32.5%. Finally, the resection was in one piece in 73.5% and incomplete in 8.6% of the adenocarcinomas. Factors independently associated with incomplete endoscopic resection were size (mm (OR 1.08, 95% CI 1.03-1.14, p = 0.002, sessile or flat morphology (OR 8.78, 95% CI 2.24-34.38, p = 0.002 and incomplete colonoscopy (OR 4.73, 95% CI 1.15-19.34, p = 0.03. Conclusions: endoscopic polypectomy allows complete resection of 91.4% of invasive adenocarcinomas on colorrectal adenoma in our series. Factors associated with incomplete resection were the size of the lesion, sessile or flat morphology and incomplete colonoscopy.Antecedentes y objetivo: la polipectomía endoscópica puede permitir la resección con intención curativa del adenocarcinoma invasivo sobre adenoma de colon. Nuestro objetivo es determinar los factores asociados a la resección endoscópica completa del adenocarcinoma invasivo. Métodos: estudio retrospectivo observacional. Se incluyeron 151 individuos con un adenocarcinoma invasivo sobre

  1. YB-1 regulates tumor growth by promoting MACC1/c-Met pathway in human lung adenocarcinoma

    Science.gov (United States)

    Xue, Xiaoyuan; Zhang, Yan; Yang, Mengying; Li, Nan; Li, Zhuoshi; Xu, Lingzhi; Jiang, Lei; Zhao, Lei; Ma, Patrick C.; Rosell, Rafael; Li, Jinxiu; Gu, Chundong

    2017-01-01

    Aberrant overexpression of the transcription/translation factor Y-box-binding protein (YB-1) is associated with poor prognosis of lung adenocarcinoma, however the underlying mechanism by which YB-1 acts has not been fully elucidated. Here, we reported that inhibition of YB-1 diminished proliferation, migration and invasion of lung adenocarcinoma cells. Interestingly, we identified metastasis associated in colon cancer-1 (MACC1) as a target of YB-1. Depletion of YB-1 markedly decreased MACC1 promoter activity and suppressed the MACC1/c-Met signaling pathway in lung adenocarcinoma cells. Additionally, chromatin immunoprecipitation (ChIP) assay demonstrated that YB-1 bound to the MACC1 promoter. Moreover, YB-1 was positively correlated with MACC1, and both proteins were over-expressed in lung adenocarcinoma tissues. The Cox-regression analysis indicated that high YB-1 expression was an independent risk factor for prognosis in enrolled patients. Furthermore, depletion of YB-1 attenuated tumorigenesis in a xenograft mouse model and reduced MACC1 expression in tumor tissues. Collectively, our data suggested that targeting YB-1 suppressed lung adenocarcinoma progression through the MACC1/c-Met pathway and that the high expression of YB-1/MACC1 is a potential prognostic marker in lung adenocarcinoma. PMID:28624808

  2. Adenocarcinoma in situ and associated human papillomavirus type distribution observed in two clinical trials of a quadrivalent human papillomavirus vaccine

    DEFF Research Database (Denmark)

    Ault, Kevin A; Joura, Elmar A; Kjaer, Susanne K

    2011-01-01

    The primary objective of this report is to describe the detection of adenocarcinoma in situ (AIS) and associated human papillomavirus (HPV) type distribution that was observed in the context of two phase 3 clinical trials of a quadrivalent HPV6/11/16/18 vaccine. In this intention-to-treat analysis...

  3. The Histone Acetyltransferase GCN5 Expression Is Elevated and Regulated by c-Myc and E2F1 Transcription Factors in Human Colon Cancer

    Science.gov (United States)

    Yin, Yan-Wei; Jin, Hong-Jian; Zhao, Wenjing; Gao, Beixue; Fang, Jiangao; Wei, Junmin; Zhang, Donna D.; Zhang, Jianing; Fang, Deyu

    2017-01-01

    The histone acetyltransferase GCN5 has been suggested to be involved in promoting cancer cell growth. But its role in human colon cancer development remains unknown. Herein we discovered that GCN5 expression is significantly upregulated in human colon adenocarcinoma tissues. We further demonstrate that GCN5 is upregulated in human colon cancer at the mRNA level. Surprisingly, two transcription factors, the oncogenic c-Myc and the proapoptotic E2F1, are responsible for GCN5 mRNA transcription. Knockdown of c-Myc inhibited colon cancer cell proliferation largely through downregulating GCN5 transcription, which can be fully rescued by the ectopic GCN5 expression. In contrast, E2F1 expression induced human colon cancer cell death, and suppression of GCN5 expression in cells with E2F1 overexpression further facilitated cell apoptosis, suggesting that GCN5 expression is induced by E2F1 as a possible negative feedback in suppressing E2F1-mediated cell apoptosis. In addition, suppression of GCN5 with its specific inhibitor CPTH2 inhibited human colon cancer cell growth. Our studies reveal that GCN5 plays a positive role in human colon cancer development, and its suppression holds a great therapeutic potential in antitumor therapy. PMID:26637399

  4. The role of the obestatin/GPR39 system in human gastric adenocarcinomas

    OpenAIRE

    Al?n, Bego?a O.; Leal-L?pez, Sa?l; Al?n, Mar?a Otero; Via?o, Patricia; Garc?a-Castro, Victoria; Mosteiro, Carlos S.; Beiras, Andr?s; Casanueva, Felipe F.; Gallego, Rosal?a; Garc?a-Caballero, Tom?s; Cami?a, Jes?s P.; Pazos, Yolanda

    2015-01-01

    Obestatin, a 23-amino acid peptide encoded by the ghrelin gene, and the GPR39 receptor were reported to be involved in the control of mitogenesis of gastric cancer cell lines; however, the relationship between the obestatin/GPR39 system and gastric cancer progression remains unknown. In the present study, we determined the expression levels of the obestatin/GPR39 system in human gastric adenocarcinomas and explored their potential functional roles. Twenty-eight patients with gastric adenocarc...

  5. Amplification and expression of a cellular oncogene (c-myc) in human gastric adenocarcinoma cells.

    Science.gov (United States)

    Shibuya, M; Yokota, J; Ueyama, Y

    1985-01-01

    Three of 16 human gastric adenocarcinoma samples, maintained as solid tumors in nude mice, were found to carry amplified c-myc genes. In two samples with a high degree of c-myc DNA amplification (15- to 30-fold), double minute chromosomes were observed in karyotype analysis. The level of c-myc RNA was markedly elevated in a rapidly growing and poorly differentiated tumor, whereas it was only slightly elevated in a slowly growing and more differentiated tumor. Images PMID:2579323

  6. Cryptolepine, isolated from Sida acuta, sensitizes human gastric adenocarcinoma cells to TRAIL-induced apoptosis.

    Science.gov (United States)

    Ahmed, Firoj; Toume, Kazufumi; Ohtsuki, Takashi; Rahman, Mahmudur; Sadhu, Samir Kumar; Ishibashi, Masami

    2011-01-01

    Bioassay guided separation of Sida acuta whole plants led to the isolation of an alkaloid, cryptolepine (1), along with two kaempferol glycosides (2-3). Compound 1 showed strong activity in overcoming TRAIL-resistance in human gastric adenocarcinoma (AGS) cells at 1.25, 2.5 and 5 μm. Combined treatment of 1 and TRAIL sensitized AGS cells to TRAIL-induced apoptosis at the aforementioned concentrations. Copyright © 2010 John Wiley & Sons, Ltd.

  7. Synchronous cecal adenocarcinoma and multiple colonic in situ carcinomas in hamartomatous polyps in a case of isolated Peutz–Jeghers syndrome

    Directory of Open Access Journals (Sweden)

    Yahia Z Gad

    2011-03-01

    Full Text Available Yahia Z Gad1, Doaa H Bakr1, Mohammad G El-Ebeidy21Department of Internal Medicine, 2Department of Surgery, Mansoura Specialized Medical Hospital, Mansoura University, Mansoura, EgyptBackground: Peutz–Jeghers syndrome (PJS is a rare autosomal dominant disease characterized by mucocutaneous pigmentation and hamartomatous polyps of the entire gastrointestinal tract. A Peutz–Jeghers polyp (PJP in a patient without pigmentation or a family history of the disease is called an isolated or solitary PJP. Individuals with PJS carry a very high risk of developing gastrointestinal (GI as well as extra-GI malignancies. This case report documents lesion multiplicity and their malignant potential in a young patient with PJS presenting in a serious condition for the first time.Case report: An 18-year-old female Egyptian patient was admitted with hematochezia and remarkable anemia. After appropriate resuscitation and consent, colonoscopic evaluation revealed seven pedunculated colonic polyps at the ascending and the transverse colon, and numerous variable-sized sessile polyps were scattered all over the colon. To establish hemostasis, endoscopic polypectomy for pedunculated polyps and argon plasma photocoagulation for the bleeding sessile polyps were performed. Histopathological examination revealed cecal adenocarcinoma in one specimen and two simultaneous in situ carcinoma at the transverse and the sigmoid colon in the mucosae of the excised histologically proven hamartomatous polyps. Additionally, one focal in situ carcinoma in the resected colon was detected.Conclusions: When considering the family history, serious GI neoplastic lesions may be unmasked in young patients with PJS who present with hematochezia, even in the absence of its characteristic mucocutaneous pigmented lesions. GI endoscopic surveillance programs should be adopted for diagnosed cases of PJS and their families. Genetic prenatal screening for early detection is the best option for

  8. [Isolation and identification of side population cells in human lung adenocarcinoma cell line A549].

    Science.gov (United States)

    Xie, Tong; Li, Li; Li, Dan-rong; Mao, Nai-quan; Liu, De-seng; Zuo, Chuan-tian; Zhang, Wei; Huang, Ding-ming

    2011-02-01

    To isolate and characterize the side population cells (SP cells) in the lung adenocarcinomas cell line A549. The protein expression of ABCG2 in human lung adenocarcinoma cell line A549 was detected by immunohistochemistry. SP and NSP cells in the cell line A549 were isolated by FACS, and their differentiation was analysed. ABCG2 expression in the two cell subsets was detected by RT-PCR. The cell growth curves, cell division indexes, cell cycles, plate clone formation tests, migration and invasion assays, chemotherapeutic susceptibility tests, tests of the intracellular drug levels, and the tumor cell implantation experiments on nude mice were applied to study the biological properties of the two cell subsets. The expression of ABCG2 in the transplanted tumor in nude mice was detected by immunohistochemistry and RT-PCR. The positive rate of ABCG2 expression in the A549 cells by immunohistochemistry was 2.13%. SP and NSP cells were isolated by FACS. The SP cells could produce both SP and NSP cells, while NSP cells only produced NSP cells. SP cells expressed ABCG2, but NSP cells did not. The proliferation and migration abilities of the two cell subsets were similar, but the invasion and tumorigenic ability of SP cells was significantly higher than that of NSP cells. The susceptibilities to DDP and its intracellular levels of the two cell subsets were similar, but the susceptibilities to 5-FU, VP16, NVB and GEM and their intracellular levels of NSP cells were significantly higher than those of the SP cells. SP cells in the human lung adenocarcinomas cell line A549 is enriched with tumor stem cells. An effective way to get lung adenocarcinomas stem cells is to isolate SP cells by FACS.

  9. Synchronous Quadruple Primary Neoplasms: Colon Adenocarcinoma, Collision Tumor of Neuroendocrine Tumor and Schwann Cell Hamartoma and Sessile Serrated Adenoma of the Appendix.

    Science.gov (United States)

    Meeks, Marshall W; Grace, Shane; Chen, Yongxin; Petterchak, James; Bolesta, Edward; Zhou, Yihua; Lai, Jin-Ping

    2016-08-01

    Quadruple synchronous primary neoplasms are very rare with only three cases reported in the English-speaking literature to date. Collision tumors are also rare entities, especially of the appendix. We herein report a case of synchronous quadruple primary neoplasm in a 95-year-old female. She was diagnosed with colon adenocarcinoma, sessile serrated adenoma of the appendix and a collision tumor composed of a well-differentiated neuroendocrine tumor and Schwann cell hamartoma. Histological examination and immunohistochemistry supported these four lesions as separate entities. This case is unique because we report the diagnosis of quadruple synchronous primary, an extremely rare occurrence, in addition to a collision tumor of the appendix. We also provide a review of the literature for synchronous neoplasms and collision tumors. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  10. A metastatic colon adenocarcinoma harboring BRAF V600E has a durable major response to dabrafenib/trametinib and chemotherapy

    Directory of Open Access Journals (Sweden)

    Williams CB

    2015-12-01

    Full Text Available Casey B Williams,1,* Caitlin McMahon,2,* Siraj M Ali,2 Mark Abramovitz,1 Kirstin A Williams,1 Jessica Klein,1 Heidi McKean,1 Roman Yelensky,2 Thomas J George Jr,3 Julia A Elvin,2 Salil Soman,4 Doron Lipson,2 Juliann Chmielecki,2 Deborah Morosini,2 Vincent A Miller,2 Philip J Stephens,2 Jeffrey S Ross,2,5 Brian Leyland-Jones1 1Avera Cancer Institute, Sioux Falls, SD, USA; 2Foundation Medicine, Inc., Cambridge, MA, USA; 3University of Florida College of Medicine, Gainesville, FL, USA; 4Beth Israel Deaconess Medical Center, Boston, MA, USA; 5Albany Medical College, Albany, NY, USA *These authors contributed equally to this work Abstract: The subset of metastatic colorectal adenocarcinomas that harbor BRAF V600E mutations are aggressive tumors with significantly shortened survival and limited treatment options. Here we present a colorectal cancer patient whose disease progressed through standard chemotherapy and who developed liver metastasis. Comprehensive genomic profiling (FoundationOne® identified a BRAF V600E mutation in the liver lesion, as well as other genomic alterations consistent with colorectal cancers. Combination therapy of dabrafenib and trametinib with standard cytotoxic chemotherapy resulted in a durable major ongoing response for the patient. This report illustrates the utility of comprehensive genomic profiling with personalized targeted therapy for aggressive metastatic colorectal adenocarcinomas. Keywords: oxaliplatin, colorectal adenocarcinoma, combination targeted therapy, BRAF mutations

  11. Multimodal nonlinear optical microscopy used to discriminate human colon cancer

    Science.gov (United States)

    Adur, Javier; Pelegati, Vitor B.; Bianchi, Mariana; de Thomaz, André A.; Baratti, Mariana O.; Carvalho, Hernandes F.; Casco, Víctor H.; Cesar, Carlos L.

    2013-02-01

    Colon cancer is one of the most diffused cancers in the Western World, ranking third worldwide in frequency of incidence after lung and breast cancers. Even if it is curable when detected and treated early, a more accurate premature diagnosis would be a suitable aim for both cancer prognostic and treatment. Combined multimodal nonlinear optical (NLO) microscopies, such as two-photon excitation fluorescence (TPEF), second-harmonic generation (SHG), third harmonic generation (THG), and fluorescence lifetime imaging microscopy (FLIM) can be used to detect morphological and metabolic changes associated with stroma and epithelial transformation in colon cancer disease. NLO microscopes provide complementary information about tissue microstructure, showing distinctive patterns between normal and malignant human colonic mucosa. Using a set of scoring methods significant differences both in the content, distribution and organization of stroma collagen fibrils, and lifetime components of NADH and FAD cofactors of human colon mucosa biopsies were found. Our results provide a framework for using NLO techniques as a clinical diagnostic tool for human colon cancer, and also suggest that the SHG and FLIM metrics could be applied to other intestinal disorders, which are characterized by abnormal cell proliferation and collagen assembly.

  12. YBX1 regulates tumor growth via CDC25a pathway in human lung adenocarcinoma

    Science.gov (United States)

    Yu, Wendan; Li, Jinxiu; Tang, Zhipeng; Yu, Zhenlong; Zhao, Lei; Zhang, Yixiang; Wang, Ziyi; Wang, Peng; Li, Yechi; Li, Fengzhou; Sun, Zhe; Xuan, Yang; Tang, Ranran; Deng, Wu-guo; Guo, Wei; Gu, Chundong

    2016-01-01

    Y-box binding protein 1 (YBX1) is involved in the multi-tumor occurrence and development. However, the regulation of YBX1 in lung tumorigenesis and the underlying mechanisms, especially its relationship with CDC25a, was remains unclear. In this study, we analyzed the expression and clinical significance of YBX1 and CDC25a in lung adenocarcinoma and identified their roles in the regulation of lung cancer growth. The retrospective analysis of 116 patients with lung adenocarcinoma indicated that YBX1 was positively correlated with CDC25a expression. The Cox-regression analysis showed only high-ranking TNM stage and low CDC25a expression were an independent risk factor of prognosis in enrolled patients. High expression of YBX1 or CDC25a protein was also observed in lung adenocarcinoma cells compared with HLF cells. ChIP assay demonstrated the binding of endogenous YBX1 to the CDC25a promoter region. Overexpression of exogenous YBX1 up-regulated the expression of the CDC25a promoter-driven luciferase. By contrast, inhibition of YBX1 by siRNA markedly decreased the capability of YBX1 binding to CDC25a promoter in A549 and H322 cells. Inhibition of YBX1 expression also blocked cell cycle progression, suppressed cell proliferation and induced apoptosis via the CDC25a pathway in vitro. Moreover, inhibition of YBX1 by siRNA suppressed tumorigenesis in a xenograft mouse model and down-regulated the expression of YBX1, CDC25a, Ki67 and cleaved caspase 3 in the tumor tissues of mice. Collectively, these results demonstrate inhibition of YBX1 suppressed lung cancer growth partly via the CDC25a pathway and high expression of YBX1/CDC25a predicts poor prognosis in human lung adenocarcinoma. PMID:27384875

  13. Previous Exposure to the Fish Parasite Anisakis as a Potential Risk Factor for Gastric or Colon Adenocarcinoma.

    Science.gov (United States)

    Garcia-Perez, Juan Carlos; Rodríguez-Perez, Rosa; Ballestero, Araceli; Zuloaga, Jaime; Fernandez-Puntero, Belen; Arias-Díaz, Javier; Caballero, María Luisa

    2015-10-01

    Anisakiasis is a global disease caused by consumption of raw or lightly cooked fish contaminated with L3 Anisakis spp. larvae. High rates of parasitization of fish worldwide make Anisakis a serious health hazard. In fact, anisakiasis is a growing disease in countries such as Spain, Italy, and Japan, where consumption of raw/marinated fish is high. Some parasitic infections have been recognized as a causative factor for human cancer. Suggested mechanisms include chronic inflammation elicited by the parasite, and a possible tumorigenic effect from certain parasitic secretions. Anisakis can produce persistent local inflammation and granuloma, and larvae have been incidentally found in gastrointestinal (GI) tumors. Our aim was to discover possible differences in the prevalence of unnoticed or asymptomatic previous Anisakis infection in GI cancer patients compared with healthy individuals. Serum levels of specific antibodies against Anisakis antigens were used as a reliable marker of previous contact with their larvae. Ninety-four participants without a previous history of Anisakis infection were prospectively allocated into 1 of 2 groups: 47 patients with GI cancer and 47 controls. Specific IgE, IgA1, and IgG1 against the Anisakis recombinant antigens Ani s 1, Ani s 5, Ani s 9, and Ani s 10 were determined by an ELISA assay. The ratio of positivity to sIgA1, rAni s 1, or rAni s 5 was significantly higher in the cancer patients than in the controls (38.30% vs 6.38%, P Anisakis infection might be a risk factor for the development of stomach or colon cancer.

  14. Analysis of enteroendocrine cell populations in the human colon

    DEFF Research Database (Denmark)

    Martins, Patricia; Fakhry, Josiane; de Oliveira, Enio Chaves

    2017-01-01

    Recent studies have shown that patterns of colocalisation of hormones in enteroendocrine cells are more complex than previously appreciated and that the patterns differ substantially between species. In this study, the human sigmoid colon is investigated by immunohistochemistry for the presence o...

  15. Estudo da expressão citofotométrica do marcador tumoral Caspase-3 no adenocarcinoma de cólon Citophotometric expression study of tumoral marker Caspase-3 on colon adenocarcinoma

    Directory of Open Access Journals (Sweden)

    João Batista Monteiro Tajra

    2007-12-01

    densidade óptica foi de 42,71 não sendo possível identificar diferença em relação a classificação de Dukes. Quanto ao lado do tumor os 11 tumores à esquerda tiveram índice de marcagem de 86,65 e densidade óptica de 43,29 e os 8 à direita tíndice de marcagem de 83,29 e densidade óptica de 39,44 não sendo possível observar diferença estatística significante. CONCLUSÕES: A caspase-3 possui alta expressão individual revelando-se marcador de boa utilidade no estudo do adenocarcinoma de cólon e da fase pró-apoptóica da sua tumorigênese pelo seu alto grau de índice de marcagem e densidade óptica. Em relação à classificação Dukes não houve diferença entre os tipos B e C, como também em relação ao lado direito e esquerdo do cólon.BACKGROUND: Colon adenocarcinoma is the second cause of cancer death in men and women, responsible for more than five million deaths each year. At the diagnosis, only 70% of tumors are resectable, 75% curative and 25% might have disease recurrence. Apoptosis is responsible for homeostatic equilibrium among cells. During the development of the cellular malignant degeneration, an abnormal apoptosis plays an important role in the neoplasm transformation. Caspase-3 is one of the most important molecules in apoptosis, considered as the principal executioner. Caspase-3 expression and its prognosis have been mentioned in a variety of study and revision as its role being emphasized since the onset of polyp formation until the malignant transformation, as apoptosis declines progressively. AIM: To evaluate the computerized image cytophotometric expression of Caspase-3 in colon adenocarcinoma; to evaluate in the respective phases of Dukes-modified Classification and to compare its expression on right-sided and left-sided colon tumors. METHODS: Nineteen recovery of sampled-tissue in paraffin blocks confirmed by hematoxylin-eosin and submitted to immunohistochemistry estreptavidin-biotin method using antibody polyclonal anti

  16. Characterizing autofluorescence generated from endogenous porphyrins in cancerous tissue of human colon: case studies

    Science.gov (United States)

    Liu, Lina; Lin, Lisheng; Li, Weihua; Yang, Changshun; Huang, Zheng; Xie, Shusen; Li, Buhong

    2013-03-01

    The aim of this case study was to explore the relationship between porphyrins and colon adenocarcinoma, and to examine the potential of porphyrin-induced fluorescence for the diagnosis of colon cancer. Further studies were carried on 8 cases ex vivo colon adenocarcinoma samples which exceptionally exhibited 635 nm fluorescence emission under 405 nm excitation. The time-resolved fluorescence spectra at 635 nm emission under 405 nm excitation were also measured and two-exponential decay fitting was performed to determine the fluorescence lifetime at 635 nm emission. Significant difference was observed between the spectra of normal and cancer tissues, which included an emission peak at 635 nm under the excitation wavelengths of 405 nm. There was also a significant difference between the fluorescence lifetimes of 635 nm emission of the normal tissue and cancer tissue (Pcolon cancers of certain patient populations.

  17. Microbial contact during pregnancy, intestinal colonization and human disease.

    Science.gov (United States)

    Rautava, Samuli; Luoto, Raakel; Salminen, Seppo; Isolauri, Erika

    2012-10-01

    Interaction with colonizing intestinal bacteria is essential for healthy intestinal and immunological development in infancy. Advances in understanding early host-microbe interactions indicate that this early microbial programming begins in utero and is substantially modulated by mode of birth, perinatal antibiotics and breastfeeding. Furthermore, it has become evident that this stepwise microbial colonization process, as well as immune and metabolic programming by the microbiota, might have a long-lasting influence on the risk of not only gastrointestinal disease, but also allergic, autoimmune and metabolic disease, in later life. Modulating early host-microbe interaction by maternal probiotic intervention during pregnancy and breastfeeding offers a promising novel tool to reduce the risk of disease. In this Review, we describe the current body of knowledge regarding perinatal microbial contact, initial intestinal colonization and its association with human disease, as well as means of modulating early host-microbe interaction to reduce the risk of disease in the child.

  18. NFAT5 promotes proliferation and migration of lung adenocarcinoma cells in part through regulating AQP5 expression

    Energy Technology Data Exchange (ETDEWEB)

    Guo, Kai, E-mail: gk161@163.com [Department of Respiration, Tangdu Hospital, Fourth Military Medical University, Xi' an 710038 (China); Department of Respiration, 161th Hospital, PLA, Wuhan 430015 (China); Jin, Faguang, E-mail: jinfag@fmmu.edu.cn [Department of Respiration, Tangdu Hospital, Fourth Military Medical University, Xi' an 710038 (China)

    2015-09-25

    The osmoregulated transcription factor nuclear factor of activated T-cells 5(NFAT5), has been found to play important roles in the development of many kinds of human cancers, including breast cancer, colon carcinoma, renal cell carcinoma and melanoma. The aim of the present study was to determine whether NFAT5 is involved in the proliferation and migration of lung adenocarcinoma cells. We found that NFAT5 was upregulated in lung adenocarcinoma cells and knockdown of NFAT5 decreased proliferation and migration of the cells, accompanied by a significant reduction in the expression of AQP5. AQP5 was upregulated in lung adenocarcinoma cells and knockdown of AQP5 also inhibited proliferation and migration of the cells as knockdown of NFAT5 did. Moreover, overexpression of NFAT5 promoted proliferation and migration of lung adenocarcinoma cells, accompanied by a significant increase in the expression of AQP5. These results indicate that NFAT5 plays important roles in proliferation and migration of human lung adenocarcinoma cells through regulating AQP5 expression, providing a new therapeutic option for lung adenocarcinoma therapy. - Highlights: • NFAT5 expression is higher in lung adenocarcinoma cells compared with normal cells. • NFAT5 knockdown decreases proliferation and migration of lung adenocarcinoma cells. • Knockdown of NFAT5 reduces AQP5 expression in human lung adenocarcinoma cells. • Overexpression of NFAT5 promotes proliferation and migration of lung adenocarcinoma cells. • Overexpression of NFAT5 increases AQP5 expression in human lung adenocarcinoma cells.

  19. EMT is the dominant program in human colon cancer

    Directory of Open Access Journals (Sweden)

    Tollenaar Rob AEM

    2011-01-01

    Full Text Available Abstract Background Colon cancer has been classically described by clinicopathologic features that permit the prediction of outcome only after surgical resection and staging. Methods We performed an unsupervised analysis of microarray data from 326 colon cancers to identify the first principal component (PC1 of the most variable set of genes. PC1 deciphered two primary, intrinsic molecular subtypes of colon cancer that predicted disease progression and recurrence. Results Here we report that the most dominant pattern of intrinsic gene expression in colon cancer (PC1 was tightly correlated (Pearson R = 0.92, P -135 with the EMT signature-- both in gene identity and directionality. In a global micro-RNA screen, we further identified the most anti-correlated microRNA with PC1 as MiR200, known to regulate EMT. Conclusions These data demonstrate that the biology underpinning the native, molecular classification of human colon cancer--previously thought to be highly heterogeneous-- was clarified through the lens of comprehensive transcriptome analysis.

  20. Down-regulation of miR-135b in colon adenocarcinoma induced by a TGF-β receptor I kinase inhibitor (SD-208

    Directory of Open Access Journals (Sweden)

    Abolfazl Akbari

    2015-09-01

    Full Text Available Objective(s:Transforming growth factor-β(TGF-β is involved in colorectal cancer (CRC. The SD-208 acts as an anti-cancer agent in different malignancies via TGF-β signaling. This work aims to show the effect of manipulation of TGF-β signaling on some miRNAs implicated in CRC. Materials and Methods: We investigated the effects of SD-208 on SW-48, a colon adenocarcinoma cell line. The cell line was treated with 0.5, 1 and 2 μM concentrations of SD-208. Then, the xenograft model of colon cancer was established by subcutaneous inoculation of SW-48 cell line into the nude mice. The animals were treated with SD-208 for three weeks. A quantitative real-time PCR was carried out for expression level analysis of selected oncogenic (miR-21, 31, 20a and 135b and suppressor-miRNAs (let7-g, miR-133b, 145 and 200c. Data were analyzed using the 2-∆∆CT method through student’s t-test via the GraphPad Prism software. Results: Our results revealed that SD-208 could significantly down-regulate the expression of one key onco-miRNA, miR-135b, in either SW-48 colon cells (P=0.006 or tumors orthotopically implanted in nude mice (P=0.018. Our in silico study also predicted that SD-208 could modulate the expression of potential downstream tumor suppressor targets of the miR135b. Conclusion: Our data provide novel evidence that anticancer effects of SD-208 (and likely other TGF-β inhibitors may be owing to their ability to regulate miRNAs expression.

  1. Characterization of gastrins and their receptor in solid human gastric adenocarcinomas.

    Science.gov (United States)

    Goetze, Jens Peter; Eiland, Signe; Svendsen, Lars Bo; Vainer, Ben; Hannibal, Jens; Rehfeld, Jens Frederik

    2013-06-01

    The gastrin and the gastrin/CCK-B receptor genes are co-expressed in several carcinomas. The primary translational product, progastrin, however, is processed to several peptides of which only those that are α-amidated at their C-terminus are receptor ligands. So far, characterization of the progastrin-derived peptides in gastric cancer has not been reported. The authors therefore examined the molecular nature of gastrin and its receptor in human gastric carcinomas. Twenty patients with adenocarcinoma underwent partial or total gastrectomy. In samples from each carcinoma, gastrin peptides were characterized, using a library of sequence-specific immunoassays. Expression was also demonstrated by immunohistochemistry. In addition, the gastrin and gastrin/CCK-B receptor gene expression was quantitated using real-time PCR, and the receptor protein demonstrated by western blotting. α-Amidated gastrins were detectable in 16 of 20 carcinomas (median concentration 2.1 pmol/g tissue; range 0-386 pmol/g tissue). The tissue concentrations correlated closely to the gastrin mRNA contents (r = 0.75, p gastrins, were detected in 19 carcinomas. Immunohistochemistry corroborated gastrin expression in carcinoma cells. Chromatography revealed extensive progastrin processing with α-amidated gastrin-34 and -17 (tyrosyl-sulfated as well as non-sulfated) as major products. Finally, gastrin/CCK-B receptor mRNA and protein were detected in all tumors. The results show that the elements for a local loop of α-amidated gastrins and their receptor are detectable in 80% of human gastric adenocarcinomas. Therefore, the results support the contention that locally expressed gastrin may be involved in the tumorigenesis of gastric adenocarcinomas.

  2. Polyamine and methionine adenosyltransferase 2A crosstalk in human colon and liver cancer

    Energy Technology Data Exchange (ETDEWEB)

    Tomasi, Maria Lauda [Division of Gastrointestinal and Liver Diseases, Keck School of Medicine of University of Southern California, Los Angeles, CA 90033 (United States); USC Research Center for Liver Diseases, Keck School of Medicine of University of Southern California, Los Angeles, CA 90033 (United States); The Southern California Research Center for Alcoholic and Pancreatic Diseases and Cirrhosis, Keck School of Medicine of University of Southern California, Los Angeles, CA 90033 (United States); Ryoo, Minjung; Skay, Anna [Division of Gastrointestinal and Liver Diseases, Keck School of Medicine of University of Southern California, Los Angeles, CA 90033 (United States); USC Research Center for Liver Diseases, Keck School of Medicine of University of Southern California, Los Angeles, CA 90033 (United States); Tomasi, Ivan; Giordano, Pasquale [Department of Colorectal Surgery, Whipps Cross University Hospital, London E11 1NR (United Kingdom); Mato, José M. [CIC bioGUNE, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (Ciberehd), Technology Park of Bizkaia, 48160 Derio, Bizkaia (Spain); Lu, Shelly C., E-mail: shellylu@usc.edu [Division of Gastrointestinal and Liver Diseases, Keck School of Medicine of University of Southern California, Los Angeles, CA 90033 (United States); USC Research Center for Liver Diseases, Keck School of Medicine of University of Southern California, Los Angeles, CA 90033 (United States); The Southern California Research Center for Alcoholic and Pancreatic Diseases and Cirrhosis, Keck School of Medicine of University of Southern California, Los Angeles, CA 90033 (United States)

    2013-07-15

    Methionine adenosyltransferase (MAT) is an essential enzyme that is responsible for the biosynthesis of S-adenosylmethionine (SAMe), the principal methyl donor and precursor of polyamines. MAT1A is expressed in normal liver and MAT2A is expressed in all extrahepatic tissues. MAT2A expression is increased in human colon cancer and in colon cancer cells treated with mitogens, whereas silencing MAT2A resulted in apoptosis. The aim of the current work was to examine the mechanism responsible for MAT2A-dependent growth and apoptosis. We found that in RKO (human adenocarcinoma cell line) cells, MAT2A siRNA treatment lowered cellular SAMe and putrescine levels by 70–75%, increased apoptosis and inhibited growth. Putrescine supplementation blunted significantly MAT2A siRNA-induced apoptosis and growth suppression. Putrescine treatment (100 pmol/L) raised MAT2A mRNA level to 4.3-fold of control, increased the expression of c-Jun and c-Fos and binding to an AP-1 site in the human MAT2A promoter and the promoter activity. In human colon cancer specimens, the expression levels of MAT2A, ornithine decarboxylase (ODC), c-Jun and c-Fos are all elevated as compared to adjacent non-tumorous tissues. Overexpression of ODC in RKO cells also raised MAT2A mRNA level and MAT2A promoter activity. ODC and MAT2A are also overexpressed in liver cancer and consistently, similar MAT2A-ODC-putrescine interactions and effects on growth and apoptosis were observed in HepG2 cells. In conclusion, there is a crosstalk between polyamines and MAT2A. Increased MAT2A expression provides more SAMe for polyamines biosynthesis; increased polyamine (putrescine in this case) can activate MAT2A at the transcriptional level. This along with increased ODC expression in cancer all feed forward to further enhance the proliferative capacity of the cancer cell. -- Highlights: • MAT2A knockdown depletes putrescine and leads to apoptosis. • Putrescine attenuates MAT2A knockdown-induced apoptosis and growth

  3. Humans, water, and the colonization of Australia

    Science.gov (United States)

    O’Grady, Damien

    2016-01-01

    The Pleistocene global dispersal of modern humans required the transit of arid and semiarid regions where the distribution of potable water provided a primary constraint on dispersal pathways. Here, we provide a spatially explicit continental-scale assessment of the opportunities for Pleistocene human occupation of Australia, the driest inhabited continent on Earth. We establish the location and connectedness of persistent water in the landscape using the Australian Water Observations from Space dataset combined with the distribution of small permanent water bodies (springs, gnammas, native wells, waterholes, and rockholes). Results demonstrate a high degree of directed landscape connectivity during wet periods and a high density of permanent water points widely but unevenly distributed across the continental interior. A connected network representing the least-cost distance between water bodies and graded according to terrain cost shows that 84% of archaeological sites >30,000 y old are within 20 km of modern permanent water. We further show that multiple, well-watered routes into the semiarid and arid continental interior were available throughout the period of early human occupation. Depletion of high-ranked resources over time in these paleohydrological corridors potentially drove a wave of dispersal farther along well-watered routes to patches with higher foraging returns. PMID:27671630

  4. Expected resolution and detectability of adenocarcinoma tumors within human breast in time-resolved images

    Science.gov (United States)

    Gandjbakhche, Amir H.; Nossal, Ralph J.; Dadmarz, Roya; Schwartzentruber, Douglas; Bonner, Robert F.

    1995-04-01

    The prospects for time-resolved optical mammography rests on the ability to detect adenocarcinoma within the breast with sufficient resolution and specificity to compete with X-ray mammography. We characterized the optical properties of an unusually large (6 cm diameter) fresh adenocarcinoma and normal breast tissue (determined by histology to be predominantly adipose tissue) obtained from a patient undergoing mastectomy. Large specimens (5 mm thick and 3 cm wide) allowed the determination of absorption and scattering coefficients and their spatial heterogeneity as probed with a 1 mm diameter laser beam at 633 nm and 800 nm utilizing total reflectance and transmittance measure with integrating spheres. The difference between scattering coefficients of the malignant tumor and those of normal (principally adipose) breast tissue at 633 nm was much greater than the heterogeneity within each sample. This scattering difference is the principal source of contrast, particularly in time-resolved images. However, the high scattering coefficient of normal breast tissue at 633 nm limits the practicality of time-resolved mammography of a human breast compressed to 5 cm. Although the scattering coefficient of the normal breast tissue decreases at 800 nm, the differences between the optical properties of normal and abnormal breast tissue also are reduced. We used these empirical results in theoretical expressions obtained from random walk theory to quantify the expected resolution, contrast, and the detected intensity of 3, 6, and 9 mm tumors within otherwise homogeneous human breasts as a function of the gating-time of time-resolved optical mammography.

  5. Emigrating Beyond Earth Human Adaptation and Space Colonization

    CERN Document Server

    Smith, Cameron M

    2012-01-01

    For four million years humankind has been actively expanding geographically and in doing so has adapted to a wide variety of hostile environments. Now we are looking towards the ultimate adaptation - the colonization of space. Emigrating Beyond Earth illustrates that this is not a technocratic endeavor, but a natural continuation of human evolution; a journey not just for the engineer and rocket scientist, but for everyman. Based on the most current understanding of our universe, human adaptation and evolution, the authors explain why space colonization must be planned as an adaptation to, rather than the conquest of, space. Emigrating Beyond Earth argues that space colonization is an insurance policy for our species, and that it isn't about rockets and robots, it's about humans doing what we've been doing for four million years: finding new places and new ways to live. Applying a unique anthropological approach, the authors outline a framework for continued human space exploration and offer a glimpse of a po...

  6. Biobanking of Fresh-Frozen Human Adenocarcinomatous and Normal Colon Tissues: Which Parameters Influence RNA Quality?

    Directory of Open Access Journals (Sweden)

    Thibaut Galissier

    Full Text Available Medical research projects become increasingly dependent on biobanked tissue of high quality because the reliability of gene expression is affected by the quality of extracted RNA. Hence, the present study aimed to determine if clinical, surgical, histological, and molecular parameters influence RNA quality of normal and tumoral frozen colonic tissues. RNA Quality Index (RQI was evaluated on 241 adenocarcinomas and 115 matched normal frozen colon tissues collected between October 2006 and December 2012. RQI results were compared to patients' age and sex, tumor site, kind of surgery, anastomosis failure, adenocarcinoma type and grade, tumor cell percentage, necrosis extent, HIF-1α and cleaved caspase-3 immunohistochemistry, and BRAF, KRAS and microsatellites status. The RQI was significantly higher in colon cancer tissue than in matched normal tissue. RQI from left-sided colonic cancers was significantly higher than RQI from right-sided cancers. The RNA quality was not affected by ischemia and storage duration. According to histological control, 7.9% of the samples were unsatisfactory because of inadequate sampling. Biobanked tumoral tissues with RQI ≥5 had lower malignant cells to stromal cells ratio than samples with RQI <5 (p <0.05. Cellularity, necrosis extent and mucinous component did not influence RQI results. Cleaved caspase-3 and HIF-1α immunolabelling were not correlated to RQI. BRAF, KRAS and microsatellites molecular status did not influence RNA quality. Multivariate analysis revealed that the tumor location, the surgical approach (laparoscopy versus open colectomy and the occurrence of anastomotic leakage were the only parameters influencing significantly RQI results of tumor samples. We failed to identify parameter influencing RQI of normal colon samples. These data suggest that RNA quality of colonic adenocarcinoma biospecimens is determined by clinical and surgical parameters. More attention should be paid during the biobanking

  7. Echinophora platyloba DC (Apiaceae crude extract induces apoptosis in human prostate adenocarcinoma cells (PC 3

    Directory of Open Access Journals (Sweden)

    Fatemeh Zare Shahneh

    2014-10-01

    Full Text Available Background: Prostate cancer is the second leading malignancy worldwide and the second prominent cause of cancer-related deaths among men. Therefore, there is a serious necessity for finding advanced alternative therapeutic measures against this lethal malignancy. In this article, we report the cytotoxicity and the mechanism of cell death of the methanolic extract prepared from Echinophora platyloba DC plant against human prostate adenocarcinoma PC 3 cell line and Human Umbilical Vein Endothelial Cells HUVEC cell line. Methods: Cytotoxicity and viability of the methanolic extract were assessed by 3-(4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide (MTT assay and dye exclusion assay. Cell death enzyme-linked immunosorbent assay (ELISA was employed to quantify the nucleosome production resulting from nuclear DNA fragmentation during apoptosis and determine whether the mechanism involves induction of apoptosis or necrosis. The cell death was identified as apoptosis using terminal deoxynucleotidyl transferase (TdT-mediated dUTP nick end labeling (TUNEL assay and DNA fragmentation gel electrophoresis. Results: E. platyloba could decrease cell viability in malignant cells in a dose- and time-dependent manner. The IC50 values against PC 3 were determined as 236.136 ± 12.4, 143.400 ± 7.2, and 69.383 ± 1.29 μg/ml after 24, 36, and 48 h, respectively, but there was no significant activity in HUVEC normal cell (IC50 > 800 μg/ml. Morphological characterizations and DNA laddering assay showed that the methanolic extract treated cells displayed marked apoptotic characteristics such as nuclear fragmentation, appearance of apoptotic bodies, and DNA laddering fragment. Increase in an early apoptotic population was observed in a dose-dependent manner. PC 3 cell death elicited by the extract was found to be apoptotic in nature based a clear indication of TUNEL assay and gel electrophoresis DNA fragmentation, which is a hallmark of apoptosis

  8. Computer treatment of the contents of some elements in the normal and pathologically altered human colon mucosa tissues obtained by INAA

    Energy Technology Data Exchange (ETDEWEB)

    Draskovic, R.J.; Bozanic, M.; Bozanic, V.; Bohus, T. (Institut za Nuklearne Nauke Boris Kidric, Belgrade (Yugoslavia))

    1984-11-01

    Distribution of some elements (Cr, Fe, Co, Sb, Sc and Zn) in normal and pathologically altered human colon mucosa tissues were investigated by INAA. The following tissues were analyzed: normal colon mucosa, colitis chronica, colitis ulcerosa, adenoma tubulare and adenocarcinoma (diagnoses were previously confirmed clinically and histopathologically). The values of contents of the elements in these tissues (Csub(x) in nkg/g) are treated by specific computer functional programs. Regression functions of these parameters were found for the altered tissues in comparison to the normal, as well as specific functional correlations of the Csub(x)/Csub(y) relations for pairs of investigated elements. The functions which characterize these relations for the investigated colon mucosa tissue were also determined.

  9. P2Y Receptors Sensitize Mouse and Human Colonic Nociceptors.

    Science.gov (United States)

    Hockley, James R F; Tranter, Michael M; McGuire, Cian; Boundouki, George; Cibert-Goton, Vincent; Thaha, Mohamed A; Blackshaw, L Ashley; Michael, Gregory J; Baker, Mark D; Knowles, Charles H; Winchester, Wendy J; Bulmer, David C

    2016-02-24

    Activation of visceral nociceptors by inflammatory mediators contributes to visceral hypersensitivity and abdominal pain associated with many gastrointestinal disorders. Purine and pyrimidine nucleotides (e.g., ATP and UTP) are strongly implicated in this process following their release from epithelial cells during mechanical stimulation of the gut, and from immune cells during inflammation. Actions of ATP are mediated through both ionotropic P2X receptors and metabotropic P2Y receptors. P2X receptor activation causes excitation of visceral afferents; however, the impact of P2Y receptor activation on visceral afferents innervating the gut is unclear. Here we investigate the effects of stimulating P2Y receptors in isolated mouse colonic sensory neurons, and visceral nociceptor fibers in mouse and human nerve-gut preparations. Additionally, we investigate the role of Nav1.9 in mediating murine responses. The application of UTP (P2Y2 and P2Y4 agonist) sensitized colonic sensory neurons by increasing action potential firing to current injection and depolarizing the membrane potential. The application of ADP (P2Y1, P2Y12, and P2Y13 agonist) also increased action potential firing, an effect blocked by the selective P2Y1 receptor antagonist MRS2500. UTP or ADP stimulated afferents, including mouse and human visceral nociceptors, in nerve-gut preparations. P2Y1 and P2Y2 transcripts were detected in 80% and 56% of retrogradely labeled colonic neurons, respectively. Nav1.9 transcripts colocalized in 86% of P2Y1-positive and 100% of P2Y2-positive colonic neurons, consistent with reduced afferent fiber responses to UTP and ADP in Na(v)1.9(-/-) mice. These data demonstrate that P2Y receptor activation stimulates mouse and human visceral nociceptors, highlighting P2Y-dependent mechanisms in the generation of visceral pain during gastrointestinal disease. Copyright © 2016 Hockley et al.

  10. Are All Mutations the Same? A Rare Case Report of Coexisting Mutually Exclusive KRAS and BRAF Mutations in a Patient with Metastatic Colon Adenocarcinoma

    Directory of Open Access Journals (Sweden)

    Anusha Vittal

    2017-01-01

    Full Text Available 29-year-old Hispanic woman presented to the clinic with complaints of abdominal pain, nausea, fatigue, and constipation. Laboratory tests indicated the presence of iron deficiency anemia and transaminitis. Imaging evaluation revealed marked hepatomegaly with multiple hepatic metastases and pelvic lymphadenopathy. Biopsy of the hepatic lesions showed adenocarcinoma positive for pan-cytokeratin, CMA5.2, villin, and CDX2. She was positive for tumor markers CA 19-9, CA-125, and CEA. Upon further evaluation, she was found to have colorectal cancer positive for KRAS and BRAF mutations. Unfortunately, her disease progressed rapidly and she expired within 3 months from the time of her first diagnosis. KRAS and BRAF mutations are rare enough to be considered virtually mutually exclusive but coexistent mutations appear to be a distinct molecular and clinical subset with aggressive course of illness, which is in dire need of new treatment strategies. Panitumumab and Cetuximab are approved for patients with wild type KRAS CRC. Vemurafenib is a potent inhibitor of the kinase domain in mutant BRAF and its use in BRAF mutated colon cancer remains to be well established. Our report highlights the need to obtain tissue samples from these patients for analysis and to evaluate the benefit of Vemurafenib in colorectal cancers.

  11. Inferring human colonization history using a copying model.

    Directory of Open Access Journals (Sweden)

    Garrett Hellenthal

    2008-05-01

    Full Text Available Genome-wide scans of genetic variation can potentially provide detailed information on how modern humans colonized the world but require new methods of analysis. We introduce a statistical approach that uses Single Nucleotide Polymorphism (SNP data to identify sharing of chromosomal segments between populations and uses the pattern of sharing to reconstruct a detailed colonization scenario. We apply our model to the SNP data for the 53 populations of the Human Genome Diversity Project described in Conrad et al. (Nature Genetics 38,1251-60, 2006. Our results are consistent with the consensus view of a single "Out-of-Africa" bottleneck and serial dilution of diversity during global colonization, including a prominent East Asian bottleneck. They also suggest novel details including: (1 the most northerly East Asian population in the sample (Yakut has received a significant genetic contribution from the ancestors of the most northerly European one (Orcadian. (2 Native North [corrected] Americans have received ancestry from a source closely related to modern North-East Asians (Mongolians and Oroquen that is distinct from the sources for native South [corrected] Americans, implying multiple waves of migration into the Americas. A detailed depiction of the peopling of the world is available in animated form.

  12. Polyamine and Methionine Adenosyltransferase 2A Crosstalk in Human Colon and Liver Cancer

    Science.gov (United States)

    Tomasi, Maria Lauda; Ryoo, Minjung; Skay, Anna; Tomasi, Ivan; Giordano, Pasquale; Mato, José M.; Lu, Shelly C.

    2013-01-01

    Methionine adenosyltransferase (MAT) is an essential enzyme that is responsible for the biosynthesis of S-adenosylmethionine (SAMe), the principal methyl donor and precursor of polyamines. MAT1A is expressed in normal liver and MAT2A is expressed in all extrahepatic tissues. MAT2A expression is increased in human colon cancer and in colon cancer cells treated with mitogens whereas silencing MAT2A resulted in apoptosis. The aim of the current work was to examine the mechanism responsible for MAT2A-dependent growth and apoptosis. We found that in RKO (human adenocarcinoma cell line) cells, MAT2A siRNA treatment lowered cellular SAMe and putrescine levels by 70 to 75%, increased apoptosis and inhibited growth. Putrescine supplementation blunted significantly MAT2A siRNA-induced apoptosis and growth suppression. Putrescine treatment (100 pmol/L) raised MAT2A mRNA level to 4.3-fold of control, increased the expression of c-Jun and c-Fos and binding to an AP-1 site in the human MAT2A promoter and the promoter activity. In human colon cancer specimens, the expression levels of MAT2A, ornithine decarboxylase (ODC), c-Jun and c-Fos are all elevated as compared to adjacent non-tumorous tissues. Overexpression of ODC in RKO cells also raised MAT2A mRNA level and MAT2A promoter activity. ODC and MAT2A are also overexpressed in liver cancer and consistently, similar MAT2A-ODC-putrescine interactions and effects on growth and apoptosis were observed in HepG2 cells. In conclusion, there is a crosstalk between polyamines and MAT2A. Increased MAT2A expression provides more SAMe for polyamines biosynthesis; increased polyamine (putrescine in this case) can activate MAT2A at the transcriptional level. This along with increased ODC expression in cancer all feed forward to further enhance the proliferative capacity of the cancer cell. PMID:23588207

  13. Accidental endoscopic finding of Anisakis simplex in human colon

    Directory of Open Access Journals (Sweden)

    Aurelia Aloia

    2011-09-01

    Full Text Available Anisakidosis is a zoonotic disease caused by the ingestion of nematodes belonging to the family of Anisakidae. Human infection is caused by intake of raw or undercooked sea fish and cephalopods infested by Anisakis larvae. We present a case of accidental endoscopic finding of an alive nematode adhering to distal ascending colon in a 32 years old man, submitted to colonoscopy owing to recent onsets of rectal bleeding of likely hemorrhoidal origin. The nematode, removed from colon by means of biopsy forceps, has been identified as L3 larvae of A. simplex by a light microscope. Histological examination of intestinal mucosa showed a mild fibrosis of lamina propria, characterized by focal lymphocytic inflammation and scattered infiltration of eosinophils. The patient reported the intake of marinated anchovies 3 days before endoscopic examination.

  14. NONO and RALY proteins are required for YB-1 oxaliplatin induced resistance in colon adenocarcinoma cell lines

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    Tsofack Serges P

    2011-11-01

    Full Text Available Abstract Background YB-1 is a multifunctional protein that affects transcription, splicing, and translation. Overexpression of YB-1 in breast cancers causes cisplatin resistance. Recent data have shown that YB-1 is also overexpress in colorectal cancer. In this study, we tested the hypothesis that YB-1 also confers oxaliplatin resistance in colorectal adenocarcinomas. Results We show for the first time that transfection of YB-1 cDNA confers oxaliplatin resistance in two colorectal cancer cell lines (SW480 and HT29 cell lines. Furthermore, we identified by mass spectrometry analyses important YB-1 interactors required for such oxaliplatin resistance in these colorectal cancer cell lines. A tagged YB-1 construct was used to identify proteins interacting directly to YB-1 in such cells. We then focused on proteins that are potentially involved in colorectal cancer progression based on the Oncomine microarray database. Genes encoding for these YB-1 interactors were also examined in the public NCBI comparative genomic hybridization database to determine whether these genes are localized to regions of chromosomes rearranged in colorectal cancer tissues. From these analyses, we obtained a list of proteins interacting with YB-1 and potentially involved in oxaliplatin resistance. Oxaliplatin dose response curves of SW480 and HT29 colorectal cancer cell lines transfected with several siRNAs corresponding to each of these YB-1 interactors were obtained to identify proteins significantly affecting oxaliplatin sensitivity upon gene silencing. Only the depletion of either NONO or RALY sensitized both colorectal cancer cell lines to oxaliplatin. Furthermore, depletion of NONO or RALY sensitized otherwise oxaliplatin resistant overexpressing YB-1 SW480 or HT29 cells. Conclusion These results suggest knocking down NONO or RALY significant counteracts oxaliplatin resistance in colorectal cancers overexpressing the YB-1 protein.

  15. Plant extracts as natural photosensitizers in photodynamic therapy: in vitro activity against human mammary adenocarcinoma MCF-7 cells

    Directory of Open Access Journals (Sweden)

    Rigo Baluyot Villacorta

    2017-04-01

    Conclusions: Two of the plant extracts used, L. racemosa and A. procera were toxic and induced apoptosis to mammary cell adenocarcinoma, MCF-7 when photoactivated. These extracts were also more toxic to human cancer than non-cancer cell lines.

  16. Irinotecan-Eluting Beads in Treating Patients With Refractory Metastatic Colon or Rectal Cancer That Has Spread to the Liver

    Science.gov (United States)

    2017-04-12

    Liver Metastases; Mucinous Adenocarcinoma of the Colon; Mucinous Adenocarcinoma of the Rectum; Recurrent Colon Cancer; Recurrent Rectal Cancer; Signet Ring Adenocarcinoma of the Colon; Signet Ring Adenocarcinoma of the Rectum; Stage IVA Colon Cancer; Stage IVA Rectal Cancer; Stage IVB Colon Cancer; Stage IVB Rectal Cancer

  17. Induction of farnesoid X receptor signaling in germ-free mice colonized with a human microbiota

    DEFF Research Database (Denmark)

    Wahlström, Annika; Kovatcheva-Datchary, Petia; Ståhlman, Marcus

    2017-01-01

    signaling in colonized mice. We colonized germ-free mice with cecal content from a mouse donor or feces from a human donor and euthanized the mice after short-term (2 weeks) or long-term (15 weeks) colonization. We analyzed the gut microbiota and BA composition and expression of FXR target genes in ileum...... and liver. We found that cecal microbiota composition differed between mice colonized with mouse and human microbiota and was stable over time. Human and mouse microbiota reduced total BA levels similarly, but the humanized mice produced less secondary BAs. The human microbiota was able to reduce the levels...... of tauro-β-muricholic acid and induce expression of FXR target genes Fgf15 and Shp in ileum after long-term colonization. We show that a human microbiota can change BA composition and induce FXR signaling in colonized mice, but the levels of secondary BAs produced are lower than in mice colonized...

  18. In vitro cytotoxicity screening of wild plant extracts from Saudi Arabia on human breast adenocarcinoma cells.

    Science.gov (United States)

    Ali, M A; Abul Farah, M; Al-Hemaid, F M; Abou-Tarboush, F M

    2014-05-23

    This study investigated the in vitro anticancer activities of a total of 14 wild angiosperms collected in Saudi Arabia. The cytotoxic activity of each extract was assessed against human breast adenocarcinoma (MCF-7) cell lines by using the MTT assay. Among the plants screened, the potential cytotoxic activity exhibited by the extract of Lavandula dentata (Lamiaceae) was identified, and we analyzed its anticancer potential by testing antiproliferative and apoptotic activity. Our results clearly show that ethanolic extract of L. dentata exhibits promising cytotoxic activity with an IC50 value of 39 μg/mL. Analysis of cell morphological changes, DNA fragmentation and apoptosis (using an Annexin V assay) also confirmed the apoptotic effect of L. dentata extract, and thus, our data call for further investigations to determine the active chemical constituent(s) and their mechanisms of inducing apoptosis.

  19. Characterization of gastrins and their receptor in solid human gastric adenocarcinomas

    DEFF Research Database (Denmark)

    Goetze, Jens Peter; Eiland, Signe; Svendsen, Lars Bo

    2013-01-01

    OBJECTIVE: The gastrin and the gastrin/CCK-B receptor genes are co-expressed in several carcinomas. The primary translational product, progastrin, however, is processed to several peptides of which only those that are α-amidated at their C-terminus are receptor ligands. So far, characterization...... of the progastrin-derived peptides in gastric cancer has not been reported. The authors therefore examined the molecular nature of gastrin and its receptor in human gastric carcinomas. MATERIALS AND METHODS: Twenty patients with adenocarcinoma underwent partial or total gastrectomy. In samples from each carcinoma......, gastrin peptides were characterized, using a library of sequence-specific immunoassays. Expression was also demonstrated by immunohistochemistry. In addition, the gastrin and gastrin/CCK-B receptor gene expression was quantitated using real-time PCR, and the receptor protein demonstrated by western...

  20. Aptamer based electrochemical sensor for detection of human lung adenocarcinoma A549 cells

    Science.gov (United States)

    Sharma, Rachna; Varun Agrawal, Ved; Sharma, Pradeep; Varshney, R.; Sinha, R. K.; Malhotra, B. D.

    2012-04-01

    We report results of the studies relating to development of an aptamer-based electrochemical biosensor for detection of human lung adenocarcinoma A549 cells. The aminated 85-mer DNA aptamer probe specific for the A549 cells has been covalently immobilized onto silane self assembled monolayer (SAM) onto ITO surface using glutaraldehyde as the crosslinker. The results of cyclic voltammetry and differential pulse voltammetry studies reveal that the aptamer functionalized bioelectrode can specifically detect lung cancer cells in the concentration range of 103 to 107 cells/ml with detection limit of 103 cells/ml within 60 s. The specificity studies of the bioelectrode have been carried out with control KB cells. No significant change in response is observed for control KB cells as compared to that of the A549 target cells.

  1. Bax is not involved in the resveratrol-induced apoptosis in human lung adenocarcinoma cells

    Science.gov (United States)

    Zhang, Wei-wei; Wang, Zhi-ping; Chen, Tong-sheng

    2010-02-01

    Resveratrol (RV) is a natural plant polyphenol widely present in foods such as grapes, wine, and peanuts. Previous studies indicate that RV has an ability to inhibit various stages of carcinogenesis and eliminate preneoplastic cells in vitro and in vivo. However, little is known about the molecular mechanism of RV-induced apoptosis in human lung adenocarcinoma (ASTC-a-1) cell. In this report, we analyzed whether Bax translocation from cytoplasm to mitochondria during RV-induced apoptosis in single living cell using onfocal microscopey. Cells were transfected with GFP-Bax plasmid. Cell counting kit (CCK-8) assay was used to assess the inhibition of RV on the cells viability. Apoptotic activity of RV was detected by Hoechst 33258 and propidium iodide (PI) staining. Our results showed that RV induced a dose-dependent apoptosis in which Bax did not translocate to mitochondrias.

  2. Human epidermal growth factor (Her-2) in gastric and colorectal adenocarcinoma.

    Science.gov (United States)

    Shabbir, Asma; Qureshi, Muhammad Asif; Mirza, Talat; Khalid, Abdullah Bin

    2017-07-01

    Gastrointestinal (GIT) malignancies are a substantial health concern. Most patients present to the clinics with advanced and un-resectable diseases, so it remains difficult to cure with the existing chemotherapeutic regimes. It is therefore extremely important to devise novel therapeutic targets in these neoplasms in order to improve patient's survival. One such target is human epidermal growth factor, also known as Her-2. Although Her-2 expression and the use of a-Her-2 medications in breast cancers is well established, but its expression and potential use as a therapeutic target in gastrointestinal malignancies remains controversial and heavily debated. This review was planned to summarise the available literature extracted from the United States National Library of Medicine (NLM) and Pubmed Central, related to expression of Her-2 in gastric and colorectal adenocarcinomas and their correlation with different parameters. Moreover, we also planned to discuss available data in support of using a-Her-2 in gastric and colorectal malignancies.

  3. High fluence laser irradiation induces reactive oxygen species generation in human lung adenocarcinoma cells

    Science.gov (United States)

    Wang, Fang; Xing, Da; Chen, Tong-Sheng

    2006-09-01

    Low-power laser irradiation (LPLI) has been used for therapies such as curing spinal cord injury, healing wound et al. Yet, the mechanism of LPLI remains unclear. Our previous study showed that low fluences laser irradiation induces human lung adenocarcinoma cells (ASTC-a-1) proliferation, but high fluences induced apoptosis and caspase-3 activation. In order to study the mechanism of apoptosis induced by high fluences LPLI further, we have measured the dynamics of generation of reactive oxygen species (ROS) using H IIDCFDA fluorescence probes during this process. ASTC-a-1 cells apoptosis was induced by He-Ne laser irradiation at high fluence of 120J/cm2. A confocal laser scanning microscope was used to perform fluorescence imaging. The results demonstrated that high fluence LPLI induced the increase of mitochondria ROS. Our studies contribute to clarify the biological mechanism of high fluence LPLI-induced cell apoptosis.

  4. Inhibition of fibroblast growth factor receptor 3-dependent lung adenocarcinoma with a human monoclonal antibody

    Directory of Open Access Journals (Sweden)

    Yongjun Yin

    2016-05-01

    Full Text Available Activating mutations in fibroblast growth factor receptor 3 (FGFR3 have been identified in multiple types of human cancer and in congenital birth defects. In human lung cancer, fibroblast growth factor 9 (FGF9, a high-affinity ligand for FGFR3, is overexpressed in 10% of primary resected non-small cell lung cancer (NSCLC specimens. Furthermore, in a mouse model where FGF9 can be induced in lung epithelial cells, epithelial proliferation and ensuing tumorigenesis is dependent on FGFR3. To develop new customized therapies for cancers that are dependent on FGFR3 activation, we have used this mouse model to evaluate a human monoclonal antibody (D11 with specificity for the extracellular ligand-binding domain of FGFR3, that recognizes both human and mouse forms of the receptor. Here, we show that D11 effectively inhibits signaling through FGFR3 in vitro, inhibits the growth of FGFR3-dependent FGF9-induced lung adenocarcinoma in mice, and reduces tumor-associated morbidity. Given the potency of FGF9 in this mouse model and the absolute requirement for signaling through FGFR3, this study validates the D11 antibody as a potentially useful and effective reagent for treating human cancers or other pathologies that are dependent on activation of FGFR3.

  5. Titanium dioxide nanoparticles activate IL8-related inflammatory pathways in human colonic epithelial Caco-2 cells

    Science.gov (United States)

    Krüger, Kristin; Cossais, François; Neve, Horst; Klempt, Martin

    2014-05-01

    Nanosized titanium dioxide (TiO2) particles are widely used as food additive or coating material in products of the food and pharmaceutical industry. Studies on various cell lines have shown that TiO2 nanoparticles (NPs) induced the inflammatory response and cytotoxicity. However, the influences of TiO2 NPs' exposure on inflammatory pathways in intestinal epithelial cells and their differentiation have not been investigated so far. This study demonstrates that TiO2 NPs with particle sizes ranging between 5 and 10 nm do not affect enterocyte differentiation but cause an activation of inflammatory pathways in the human colon adenocarcinoma cell line Caco-2. 5 and 10 nm NPs' exposures transiently induce the expression of ICAM1, CCL20, COX2 and IL8, as determined by quantitative PCR, whereas larger particles (490 nm) do not. Further, using nuclear factor (NF)-κB reporter gene assays, we show that NP-induced IL8 mRNA expression occurs, in part, through activation of NF-κB and p38 mitogen-activated protein kinase pathways.

  6. Variational image segmentation for endoscopic human colonic aberrant crypt foci.

    Science.gov (United States)

    Figueiredo, Isabel N; Figueiredo, Pedro N; Stadler, Georg; Ghattas, Omar; Araujo, Adérito

    2010-04-01

    The aim of this paper is to introduce a variational image segmentation method for assessing the aberrant crypt foci (ACF) in the human colon captured in vivo by endoscopy. ACF are thought to be precursors for colorectal cancer, and therefore their early detection may play an important clinical role. We enhance the active contours without edges model of Chan and Vese to account for the ACF's particular structure. We employ level sets to represent the segmentation boundaries and discretize in space by finite elements and in (artificial) time by finite differences. The approach is able to identify the ACF, their boundaries, and some of the internal crypts' orifices.

  7. Coexpression of receptor tyrosine kinase AXL and EGFR in human primary lung adenocarcinomas.

    Science.gov (United States)

    Wu, Zhenzhou; Bai, Fan; Fan, Liyun; Pang, Wenshuai; Han, Ruiyu; Wang, Juan; Liu, Yueping; Yan, Xia; Duan, Huijun; Xing, Lingxiao

    2015-12-01

    AXL has been identified as a tyrosine kinase switch that causes resistance to inhibitors targeting epidermal growth factor receptor (EGFR) signaling in non-small cell lung cancer (NSCLC). However, the relationship between 2 receptor tyrosine kinases, AXL and EGFR, and the relevance of AXL expression with EGFR mutation status in treatment-naive human NSCLCs remain uncertain. In this study, we evaluated the coexpression pattern of AXL, EGFR, and pEGFR(1068) in 109 lung adenocarcinoma patients with or without an EGFR mutation. There were 68 (62.4%) patients with tumors harboring EGFR mutations such as 19 del and/or L858R; 2 patients were T790M positive. The expression of AXL, EGFR, and pEGFR(1068) was detected in 60 (55%), 68 (62.4%), and 57 (52.3%) of 109 patients, respectively. The positive rates of EGFR and pEGFR(1068) were associated with the L858R mutation alone or with the 19 del and L858R mutation status. Further analysis indicated that the percentage of AXL(+)/EGFR(+)/pEGFR(1068) coexpression in 68 EGFR-activating mutations patients was significantly higher than that in 39 EGFR wild-type patients (30.9% versus 10.3%, P=.015). Furthermore, in the subgroup of AXL(+) patients (35 mutation(+) and 23 wild-type patients), the coexpression rates of AXL(+)/pEGFR(1068+) and AXL(+)/EGFR(+)/pEGFR(1068+) in patients with EGFR mutations were significantly higher compared with those in wild-type patients (both P<.05). Our study emphasized that the AXL and EGFR receptor tyrosine kinases were coexpressed in a subgroup of treatment-naive lung adenocarcinomas with or without EGFR mutations. Anti-AXL therapeutics delivered up front in combination with an EGFR inhibitor might prevent or delay resistance in patients with AXL-positive, EGFR-mutant, or wild-type NSCLC. Copyright © 2015 Elsevier Inc. All rights reserved.

  8. Lebein, a snake venom disintegrin, suppresses human colon cancer cells proliferation and tumor-induced angiogenesis through cell cycle arrest, apoptosis induction and inhibition of VEGF expression.

    Science.gov (United States)

    Zakraoui, Ons; Marcinkiewicz, Cezary; Aloui, Zohra; Othman, Houcemeddine; Grépin, Renaud; Haoues, Meriam; Essafi, Makram; Srairi-Abid, Najet; Gasmi, Ammar; Karoui, Habib; Pagès, Gilles; Essafi-Benkhadir, Khadija

    2017-01-01

    Lebein, is an heterodimeric disintegrin isolated from Macrovipera lebetina snake venom that was previously characterized as an inhibitor of ADP-induced platelet aggregation. In this study, we investigated the effect of Lebein on the p53-dependent growth of human colon adenocarcinoma cell lines. We found that Lebein significantly inhibited LS174 (p53wt), HCT116 (p53wt), and HT29 (p53mut) colon cancer cell viability by inducing cell cycle arrest through the modulation of expression levels of the tumor suppression factor p53, cell cycle regulating proteins cyclin D1, CDK2, CDK4, retinoblastoma (Rb), CDK1, and cyclin-dependent kinase inhibitors p21 and p27. Interestingly, Lebein-induced apoptosis of colon cancer cells was dependent on their p53 status. Thus, in LS174 cells, cell death was associated with PARP cleavage and the activation of caspases 3 and 8 while in HCT116 cells, Lebein induced caspase-independent apoptosis through increased expression of apoptosis inducing factor (AIF). In LS174 cells, Lebein triggers the activation of the MAPK ERK1/2 pathway through induction of reactive oxygen species (ROS). It also decreased cell adhesion and migration to fibronectin through down regulation of α5β1 integrin. Moreover, Lebein significantly reduced the expression of two angiogenesis stimulators, Vascular Endothelial Growth Factor (VEGF) and Neuropilin 1 (NRP1). It inhibited the VEGF-induced neovascularization process in the quail embryonic CAM system and blocked the development of human colon adenocarcinoma in nude mice. Overall, our work indicates that Lebein may be useful to design a new therapy against colon cancer. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  9. Erythropoietin receptor expression is a potential prognostic factor in human lung adenocarcinoma.

    Directory of Open Access Journals (Sweden)

    Anita Rózsás

    Full Text Available Recombinant human erythropoietins (rHuEPOs are used to treat cancer-related anemia. Recent preclinical studies and clinical trials, however, have raised concerns about the potential tumor-promoting effects of these drugs. Because the clinical significance of erythropoietin receptor (EPOR signaling in human non-small cell lung cancer (NSCLC also remains controversial, our aim was to study whether EPO treatment modifies tumor growth and if EPOR expression has an impact on the clinical behavior of this malignancy. A total of 43 patients with stage III-IV adenocarcinoma (ADC and complete clinicopathological data were included. EPOR expression in human ADC samples and cell lines was measured by quantitative real-time polymerase chain reaction. Effects of exogenous rHuEPOα were studied on human lung ADC cell lines in vitro. In vivo growth of human ADC xenografts treated with rHuEPOα with or without chemotherapy was also assessed. In vivo tumor and endothelial cell (EC proliferation was determined by 5-bromo-2'-deoxy-uridine (BrdU incorporation and immunofluorescent labeling. Although EPOR mRNA was expressed in all of the three investigated ADC cell lines, rHuEPOα treatment (either alone or in combination with gemcitabine did not alter ADC cell proliferation in vitro. However, rHuEPOα significantly decreased tumor cell proliferation and growth of human H1975 lung ADC xenografts. At the same time, rHuEPOα treatment of H1975 tumors resulted in accelerated tumor endothelial cell proliferation. Moreover, in patients with advanced stage lung ADC, high intratumoral EPOR mRNA levels were associated with significantly increased overall survival. This study reveals high EPOR level as a potential novel positive prognostic marker in human lung ADC.

  10. Radiofrequency ablation combined with KS-IL2 immunocytokine (EMD 273066) results in an enhanced antitumor effect against murine colon adenocarcinoma.

    Science.gov (United States)

    Johnson, Erik E; Yamane, Brett H; Buhtoiarov, Ilia N; Lum, Hillary D; Rakhmilevich, Alexander L; Mahvi, David M; Gillies, Stephen D; Sondel, Paul M

    2009-08-01

    Radiofrequency ablation (RFA) is a common treatment modality for surgically unresectable tumors. However, there is a high rate of both local and systemic recurrence. In this preclinical study, we sought to enhance the antitumor effect of RFA by combining it with huKS-IL2 immunocytokine [tumor-specific monoclonal antibody fused to interleukin-2 (IL2)] in mice bearing CT26-KS colon adenocarcinoma. Mice were treated with RFA, huKS-IL2 via intratumoral injection, or combination therapy. Treatment of mice bearing s.c. tumors with RFA and huKS-IL2 resulted in significantly greater tumor growth suppression and enhanced survival compared with mice treated with RFA or huKS-IL2 alone. When subtherapeutic regimens of RFA or huKS-IL2 were used, tumors progressed in all treated mice. In contrast, the combination of RFA and immunocytokine resulted in complete tumor resolution in 50% of mice. Treatment of a tumor with RFA and intratumoral huKS-IL2 also showed antitumor effects against a distant untreated tumor. Tumor-free mice after treatment with RFA and huKS-IL2 showed immunologic memory based on their ability to reject subsequent challenges of CT26-KS and the more aggressive parental CT26 tumors. Flow cytometry analysis of tumor-reactive T cells from mice with complete tumor resolution showed that treatment with RFA and huKS-IL2 resulted in a greater proportion of cytokine-producing CD4 T cells and CD8 T cells compared with mice treated with RFA or huKS-IL2 alone. These results show that the addition of huKS-IL2 to RFA significantly enhances the antitumor response in this murine model, resulting in complete tumor resolution and induction of immunologic memory.

  11. Strawberry-Tree Honey Induces Growth Inhibition of Human Colon Cancer Cells and Increases ROS Generation: A Comparison with Manuka Honey.

    Science.gov (United States)

    Afrin, Sadia; Forbes-Hernandez, Tamara Y; Gasparrini, Massimiliano; Bompadre, Stefano; Quiles, José L; Sanna, Gavino; Spano, Nadia; Giampieri, Francesca; Battino, Maurizio

    2017-03-11

    Honey is a natural product known to modulate several biological activities including cancer. The aim of the present study was to examine the phytochemical content and the antioxidant activity of Strawberry tree ( Arbutus unedo ) honey (STH) and its cytotoxic properties against human colon adenocarcinoma (HCT-116) and metastatic (LoVo) cell lines in comparison with Manuka ( Leptospermum scoparium ) honey (MH). Several unifloral STH and MH were analyzed for their phenolic, flavonoid, amino acid and protein contents, as well as their radical scavenging activities. STH from the Berchidda area showed the highest amount of phenolic, flavonoid, amino acid and protein content, and antioxidant capacity compared to MH. Both STH and MH induced cytotoxicity and cell death in a dose- and time-dependent manner in HCT-116 and LoVo cells, with less toxicity on non-cancer cells. Compared to MH, STH showed more effect at lower concentrations on HCT-116 and LoVo cells. In addition, both honeys increased intracellular reactive oxygen species (ROS) generation. In HCT-116 cells, STH and MH induced similar ROS production but in LoVo cells STH induced a higher percentage of ROS compared to MH. Our results indicate that STH and MH can induce cell growth inhibition and ROS generation in colon adenocarcinoma and metastatic cells, which could be due to the presence of phytochemicals with antioxidant properties. These preliminary results are interesting and suggest a potential chemopreventive action which could be useful for further studies in order to develop chemopreventive agents for colon cancer.

  12. Deregulation of the CEACAM expression pattern causes undifferentiated cell growth in human lung adenocarcinoma cells.

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    Bernhard B Singer

    Full Text Available CEACAM1, CEA/CEACAM5, and CEACAM6 are cell adhesion molecules (CAMs of the carcinoembryonic antigen (CEA family that have been shown to be deregulated in lung cancer and in up to 50% of all human cancers. However, little is known about the functional impact of these molecules on undifferentiated cell growth and tumor progression. Here we demonstrate that cell surface expression of CEACAM1 on confluent A549 human lung adenocarcinoma cells plays a critical role in differentiated, contact-inhibited cell growth. Interestingly, CEACAM1-L, but not CEACAM1-S, negatively regulates proliferation via its ITIM domain, while in proliferating cells no CEACAM expression is detectable. Furthermore, we show for the first time that CEACAM6 acts as an inducer of cellular proliferation in A549 cells, likely by interfering with the contact-inhibiting signal triggered by CEACAM1-4L, leading to undifferentiated anchorage-independent cell growth. We also found that A549 cells expressed significant amounts of non-membrane anchored variants of CEACAM5 and CEACAM6, representing a putative source for the increased CEACAM5/6 serum levels frequently found in lung cancer patients. Taken together, our data suggest that post-confluent contact inhibition is established and maintained by CEACAM1-4L, but disturbances of CEACAM1 signalling by CEACAM1-4S and other CEACAMs lead to undifferentiated cell growth and malignant transformation.

  13. Effects of NVP-BEZ235 on the proliferation, migration, apoptosis and autophagy in HT-29 human colorectal adenocarcinoma cells.

    Science.gov (United States)

    Yu, Yang; Yu, Xiaofeng; Ma, Jianxia; Tong, Yili; Yao, Jianfeng

    2016-07-01

    The phosphoinositide 3 kinase (PI3K)/Akt/mammalian target of the rapamycin (mTOR) pathway plays a significant role in colorectal adenocarcinoma. NVP-BEZ235 (dactolisib) is a novel dual inhibitor of PI3K/mTOR. The effects of NVP-BEZ235 in human colorectal adenocarcinoma are still unclear. In the present study, we aimed to explore the proliferation, migration, apoptosis and autophagy in HT-29 human colorectal adenocarcinoma cells. HT-29 human colorectal adenocarcinoma cells were treated with NVP-BEZ235 (0, 0.001, 0.01, 0.1, 1 and 3 µM) for 24 and 48 h, respectively. Cells were also treated with NVP-BEZ235 (0.1 µM), DDP (100, 300 and 1,000 µM), and NVP-BEZ235 (0.1 µM) combined with DDP (100, 300 and 1,000 µM) respectively, and cultured for 24 h after treatment. MTT assay was utilized to evaluate the effects of NVP-BEZ235 alone or NVP-BEZ235 combined with cis-diamminedichloroplatinum (DDP) on proliferation of HT-29 cells. Cell wound-scratch assay was used detect cell migration. In addition, expression of microtubule-associated proteins 1A/1B light chain 3B (MAP1LC3B and LC3B) in HT-29 cells was detected by immunofluorescence at 48 h after NVP-BEZ235 (1 µM) treatment. Expression of proteins involved in cell cycle and proliferation (p-Akt, p-mTOR and cyclin D1), apoptosis (cleaved caspase-3), and autophagy (cleaved LC3B and Beclin-1) were detected by western blot analysis. NVP-BEZ235 inhibited the proliferation and migration of HT-29 human colorectal adenocarcinoma cells. NVP-BEZ235 decreased protein expression of p-Akt, p-mTOR and cyclin D1, and increased protein expression of cleaved caspase-3, cleaved LC3B and Beclin-1 as the concentrations and the incubation time of NVP-BEZ235 increased. In addition, NVP-BEZ235 and DDP had synergic effects in inhibiting cell proliferation and migration. The expression of protein involved in apoptosis (cleaved caspase-3) was higher in drug combination group compared to the NVP-BEZ235 single treatment group. NVP-BEZ235

  14. Colonic transit time is related to bacterial metabolism and mucosal turnover in the human gut

    DEFF Research Database (Denmark)

    Roager, Henrik Munch; Hansen, Lea Benedicte Skov; Bahl, Martin Iain

    transit time and the gut microbial composition and metabolism, we assessed the colonic transit time of 98 subjects using radiopaque markers, and profiled their gut microbiota by16S rRNA gene sequencing and their urine metabolome by ultra performance liquid chromatography mass spectrometry. Based...... on correlation analyses, we show that colonic transit time is associated with overall gut microbial composition, diversity and metabolism. A relatively prolonged colonic transit time associates with high microbial species richness and a shift in colonic metabolism from carbohydrate fermentation to protein......Little is known about how colonic transit time relates to human colonic metabolism, and its importance for host health, although stool consistency, a proxy for colonic transit time, has recently been negatively associated with gut microbial richness. To address the relationships between colonic...

  15. Effects of ozone exposure on human epithelial adenocarcinoma and normal fibroblasts cells.

    Science.gov (United States)

    Poma, Anna; Colafarina, Sabrina; Aruffo, Eleonora; Zarivi, Osvaldo; Bonfigli, Antonella; Di Bucchianico, Sebastiano; Di Carlo, Piero

    2017-01-01

    Previous studies show variable ozone cytotoxicity and genotoxicity in cell cultures, laboratory animals and humans directly exposed to tropospheric ozone. The aim of this study was therefore to investigate and compare the cyto and genotoxic effects of ozone using adenocarcinoma human alveolar basal epithelial cells A549 and normal human fibroblasts Hs27. A cell culture chamber with controlled atmosphere (a simulation reactor) was built to inject a flow of 120 ppb of ozone, which is two times the threshold value for the protection of human health, fixed by the EU legislation. Cell proliferation was evaluated by a luminescent cell viability assay while we assessed the genotoxic potential of ozone by the induction of micronuclei as well as evaluating DNA strand breaks by the induction of micronuclei evaluated by means of the cytokinesis-block micronucleus (CBMN) assay as well as evaluating DNA strand breaks by Alkaline Comet Assay (CA) or Comet Assay. A549 cells viability decreases significantly at 24 hours treatment with 120 ppb of O3 while at 48 hours and 72 hours O3 treated cells viability doesn't differ in respect to the control. However a significative decrease of A549 viability is shown at 72 hours vs. 48 hours in both treated and not-treated cells. The viability trend in the Hs27 cells did not show any significant changes in treated samples compared to the control in all conditions. The two genotoxicity biomarkers, the micronucleus and the comet tests, showed in both the cell types exposed to ozone, a significant increase in the number of micronuclei and in the tail DNA % in respect to the control even if at different times/cell type. Moreover, we found that O3 provokes genotoxic effects more evident in A549 cancer cells than in normal fibroblasts Hs27 ones. We applied a cell growth simulation model referred to ozone treated or not cell lines to confirm that the ozone exposure causes a slackening in the cells replication.

  16. The modern human colonization of western Eurasia: when and where?

    Science.gov (United States)

    Hublin, Jean-Jacques

    2015-06-01

    Dating the timing of the replacement of local Neandertal populations by modern humans in western Eurasia at the dawn of the Upper Palaeolithic remains challenging due to the scarcity of the palaeontological evidence and to the complexity of the archaeological record. Furthermore, key specimens have been discovered in the course of excavations that unfortunately did not meet today's archaeological standards. The importance of site-formation processes in the considered time period makes it sometimes difficult to precisely assign fragmentary remains a posteriori to distinct techno-complexes. The improvements in dating methods have however allowed for the clarification of many chronological issues in the past decade. Archaeological and palaeontological evidence strongly suggest that the initial modern colonization of eastern Europe and central Asia should be related to the spread of techno-complexes assigned to the Initial Upper Palaeolithic. This first expansion may have started as early as 48 ka cal BP. The earliest phases of the Aurignacian complex (Protoaurignacian and Early Aurignacian) seem to represent another modern wave of migrations, starting in the Levant area. The expansion of this techno-complex throughout Europe completed the modern colonization of the continent. The interpretation of a third group of industries referred to as "transitional assemblages" in western and central Europe is much debated. At least in part, these assemblages might have been produced by Neandertal groups that may have survived until c. 41 ka cal BP, according to the directly dated Neandertal specimens of Saint-Césaire (France) and Spy (Belgium).

  17. Effects of the Spider Venom on proliferation of Human Lung Adenocarcinoma Cell A549

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    Zengxiang HU

    2010-10-01

    Full Text Available Background and objective The spider venom may inspire new drugs to treat cancer. The aim of this study is to investigate the effects and mechanisms of spider venom on lung adenocarcinoma cell A549. Methods The proliferation of lung adenocarcinoma A549 cells was detected by MTT. The apoptosis rate was observed with MTT assay and flow cytometer. The activity of catalase was detected by colorimetry. The malondialdehyde (MDA content was determined by improved thiobarbituric acid fluorometric method. The expression of P38MAPK protein was analyzed with Western blot. Results Spider venom can remarkably inhibite the proliferation of lung adenocarcinoma A549 cells, increased activity of catalase and MDA content, down-regulated expression of P38MAPK compared with the control group. Conclusion The reduced proliferation of lung adenocarcinoma A549 cells by spider venom is may be associated with the increased of activity of catalase and MDA content and decreased expression of P38MAPK.

  18. Effects of the Spider Venom on proliferation of Human Lung Adenocarcinoma Cell A549

    OpenAIRE

    Zengxiang HU; Du, Yulei; Quanxi LIU; Wang, Yuan

    2010-01-01

    Background and objective The spider venom may inspire new drugs to treat cancer. The aim of this study is to investigate the effects and mechanisms of spider venom on lung adenocarcinoma cell A549. Methods The proliferation of lung adenocarcinoma A549 cells was detected by MTT. The apoptosis rate was observed with MTT assay and flow cytometer. The activity of catalase was detected by colorimetry. The malondialdehyde (MDA) content was determined by improved thiobarbituric acid fluorometric met...

  19. Cartilage oligomeric matrix protein (COMP)-mediated cell differentiation to proteolysis mechanism networks from human normal adjacent tissues to lung adenocarcinoma.

    Science.gov (United States)

    Wang, Lin; Huang, Juxiang; Jiang, Minghu; Diao, Haizhen; Zhou, Huilei; Li, Xiaohe; Chen, Qingchun; Jiang, Zhenfu; Feng, Haitao; Wolfl, Stefan

    2013-01-01

    To understand cartilage oligomeric matrix protein (COMP) mechanism network from human normal adjacent tissues to lung adenocarcinoma. COMP complete different activated (all no positive correlation, Pearson CC lung adenocarcinoma compared with lower human normal adjacent tissues from the corresponding COMP-stimulated (≥0.25) or inhibited (Pearson CC ≤ -0.25) overlapping molecules of Pearson correlation coefficient (CC) and GRNInfer, respectively. COMP complete different activated and inhibited (all no positive correlation, Pearson CC lung adenocarcinoma and lower human normal adjacent tissues were constructed by integration of Pearson CC, GRNInfer and GO. As visualized by integration of GO, KEGG, GenMAPP, BioCarta and Disease, we deduced COMP complete different activated and inhibited network in higher lung adenocarcinoma and lower human normal adjacent tissues. As visualized by GO, KEGG, GenMAPP, BioCarta and disease database integration, we proposed mainly that the mechanism and function of COMP complete different activated network in higher lung adenocarcinoma was involved in COMP activation with matrix-localized insulin-like factor coupling carboxypeptidase to metallopeptidase-induced proteolysis, whereas the corresponding inhibited network in lower human normal adjacent tissues participated in COMP inhibition with nucleus-localized vasculogenesis, B and T cell differentiation and neural endocrine factors coupling pyrophosphatase-mediated proteolysis. However, COMP complete different inhibited network in higher lung adenocarcinoma included COMP inhibition with nucleus-localized chromatin maintenance, licensing and assembly factors coupling phosphatase-inhibitor to cytokinesis regulators-mediated cell differentiation, whereas the corresponding activated network in lower human normal adjacent tissues contained COMP activation with cytolplasm-localized translation elongation factor coupling fucosyltransferase to ubiquitin-protein ligase-induced cell

  20. Comparative Proteomic Analysis of Human Lung Adenocarcinoma Cisplatin-resistant Cell Strain A549/CDDP

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    Sien SHI

    2009-11-01

    Full Text Available Background and objective Chemotherapy plays an important role in the comprehensive therapy of lung cancer. However, the drug-resistance often causes the failure of the chemotherapy. The aim of this study is to identify differently expressed protein before and after cisplatin resistance of human lung adenocarcinoma cell A549 by proteomic analysis. Methods Cisplatin-resistant cell strain A549/CDDP was established by combining gradually increasing concentration of cisplatin with large dosage impact. Comparative proteomic analysis of A549 and A549/CDDP were carried out by means of two-dimensional gel electrophoresis. The differentially expressed proteins were detected and identified by MALDI-TOF mass spectrometry. Results Eighty-two differentially expressed proteins were screened by analysis the electrophoretic maps of A549 and A549/CDDP. Six differential proteins were analyzed by peptide mass fingerprinting. Glucose regulating protein 75, ribosomal protein S4, mitochondrial ATP synthase F1 complex beta subunit and immunoglobulin heavy chain variable region were identified. All four differentially expressed proteins were over-expressed in A549/CDDP, whereas low-expressed or no-expressed in A549. Conclusion These differentially expressed proteins give some clues to elucidate the mechanism of lung cancer cell resistant of cisplatin, providing the basis of searching for potential target of chemotherapy of lung cancer.

  1. Inositol Hexakisphosphate Mediates Apoptosis in Human Breast Adenocarcinoma MCF-7 Cell Line via Intrinsic Pathway

    Science.gov (United States)

    Agarwal, Rakhee; Ali, Nawab

    2010-04-01

    Inositol polyphosphates (InsPs) are naturally occurring compounds ubiquitously present in plants and animals. Inositol hexakisphosphate (InsP6) is the most abundant among all InsPs and constitutes the major portion of dietary fiber in most cereals, legumes and nuts. Certain derivatives of InsPs also regulate cellular signaling mechanisms. InsPs have also been shown to reduce tumor formation and induce apoptosis in cancerous cells. Therefore, in this study, the effects of InsPs on apoptosis were studied in an attempt to investigate their potential anti-cancer therapeutic application and understand their mechanism of action. Acridine orange and ethidium bromide staining suggested that InsP6 dose dependently induced apoptosis in human breast adenocarcinoma MCF-7 cells. Among InsPs tested (InsP3, InsP4, InsP5, and InsP6), InsP6 was found to be the most effective in inducing apoptosis. Furthermore, effects of InsP6 were found most potent inducing apoptosis. Etoposide, the drug known to induce apoptosis in both in vivo and in vitro, was used as a positive control. Western blotting experiments using specific antibodies against known apoptotic markers suggested that InsP6 induced apoptotic changes were mediated via an intrinsic apoptotic pathway.

  2. Apoptosis signal-regulating kinase 1 mediates denbinobin-induced apoptosis in human lung adenocarcinoma cells

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    Pan Shiow-Lin

    2009-05-01

    Full Text Available Abstract In the present study, we explore the role of apoptosis signal-regulating kinase 1 (ASK1 in denbinobin-induced apoptosis in human lung adenocarcinoma (A549 cells. Denbinobin-induced cell apoptosis was attenuated by an ASK1 dominant-negative mutant (ASK1DN, two antioxidants (N-acetyl-L-cysteine (NAC and glutathione (GSH, a c-Jun N-terminal kinase (JNK inhibitor (SP600125, and an activator protein-1 (AP-1 inhibitor (curcumin. Treatment of A549 cells with denbinobin caused increases in ASK1 activity and reactive oxygen species (ROS production, and these effects were inhibited by NAC and GSH. Stimulation of A549 cells with denbinobin caused JNK activation; this effect was markedly inhibited by NAC, GSH, and ASK1DN. Denbinobin induced c-Jun phosphorylation, the formation of an AP-1-specific DNA-protein complex, and Bim expression. Bim knockdown using a bim short interfering RNA strategy also reduced denbinobin-induced A549 cell apoptosis. The denbinobin-mediated increases in c-Jun phosphorylation and Bim expression were inhibited by NAC, GSH, SP600125, ASK1DN, JNK1DN, and JNK2DN. These results suggest that denbinobin might activate ASK1 through ROS production to cause JNK/AP-1 activation, which in turn induces Bim expression, and ultimately results in A549 cell apoptosis.

  3. ATRA and Genistein synergistically inhibit the metastatic potential of human lung adenocarcinoma cells.

    Science.gov (United States)

    Cheng, Ji; Qi, Jun; Li, Xue-Tao; Zhou, Kun; Xu, Jing-Han; Zhou, Yong; Zhang, Guo-Qiang; Xu, Jian-Ping; Zhou, Ren-Jie

    2015-01-01

    This study was to investigate the effects of all-trans retinoic acid (ATRA) in combination with Genistein on the proliferation, expression of apoptosis related proteins and adhesion molecules (MUC1 and ICAM-1) and invasiveness of A549 cells, aiming to investigate whether combined therapy of ATRA and Genistein is superior to monotherapy in suppressing metastasis of lung cancer cells. ATRA, Genistein and both were used to treat human lung adenocarcinoma cells (A549 cells). Immunohistochemistry was done for MUC1 expression, flow cytometry for ICAM-1 expression, fluorescence quantitative PCR for MUC1 expression and Western blot assay for the expressions of cell cycle related proteins (CDK4, Rb and p-ERK1/2) and apoptosis related proteins (Bax and Bcl-2). Cells were seeded into Matrigel pre-coated Transwell chambers, and the migrating cells were counted. Combined treatment with ATRA and Genistein was able to reduce the expressions of Bcl-2, MUC1 and ICAM-1 and exerted synergistic effects to inhibit the invasion of A549 cells. ATRA and Genistein may synergistically inhibit MUC1 and ICAM-1 expressions and affect the expressions of cell cycle related proteins (CDK4, Rb and p-ERK1/2) and apoptosis related proteins (Bax and Bcl-2), inhibit the metastatic potential of lung cancer A549 cells.

  4. Enhancement of Radiation Effects by Ursolic Acid in BGC-823 Human Adenocarcinoma Gastric Cancer Cell Line.

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    Yang Yang

    Full Text Available Recent research has suggested that certain plant-derived polyphenols, i.e., ursolic acid (UA, which are reported to have antitumor activities, might be used to sensitize tumor cells to radiation therapy by inhibiting pathways leading to radiation therapy resistance. This experiment was designed to investigate the effects and possible mechanism of radiosensitization by UA in BGC-823 cell line from human adenocarcinoma gastric cancer in vitro. UA caused cytotoxicity in a dose-dependent manner, and we used a sub-cytotoxicity concentration of UA to test radioenhancement efficacy with UA in gastric cancer. Radiosensitivity was determined by clonogenic survival assay. Surviving fraction of the combined group with irradiation and sub-cytotoxicity UA significantly decreased compared with the irradiation group. The improved radiosensitization efficacy was associated with enhanced G2/M arrest, increased reactive oxygen species (ROS, down-regulated Ki-67 level and improved apoptosis. In conclusion, as UA demonstrated potent antiproliferation effect and synergistic effect, it could be used as a potential drug sensitizer for the application of radiotherapy.

  5. Involvement of ERK1/2, p38 MAPK, and PI3K/Akt signaling pathways in the regulation of cell cycle progression by PTHrP in colon adenocarcinoma cells.

    Science.gov (United States)

    Calvo, Natalia; Martín, María Julia; de Boland, Ana Russo; Gentili, Claudia

    2014-08-01

    Parathyroid hormone-related peptide (PTHrP) is distributed in most fetal and adult tissues, and its expression correlates with the severity of colon carcinoma. Recently we obtained evidence that in Caco-2 cells, a cell line from human colorectal adenocarcinoma, exogenous PTHrP increases the number of live cells, via ERK1/2, p38 MAPK, and PI3-kinase and induces the expression of cyclin D1, a cell cycle regulatory protein. In this study, we further investigated the role of PTHrP in the regulation of the cell cycle progression in these intestinal cells. Flow cytometry analysis revealed that PTHrP treatment diminishes the number of cells in the G0/G1 phase and increases the number in both S and G2/M phases. The hormone increases the expression of CDK6 and diminishes the amount of negative cell cycle regulators p27Kip1, p15INK4B, and p53. However, PTHrP does not modify the expression of cyclin D3, CDK4, and p16INK4A. In addition, inhibitors of ERK1/2 (PD98059), p38 MAPK (SB203580), and PI3Kinase (LY294002) reversed PTHrP response in Caco-2 cells. Taken together, our results suggest that PTHrP positively modulates cell cycle progression and changes the expression of proteins involved in cell cycle regulation via ERK1/2, p38 MAPK, and PI3K signaling pathways in Caco-2 cells.

  6. Pharmacogenomics of the polyamine analog 3,8,13,18-tetraaza-10,11-[(E)-1,2-cyclopropyl]eicosane tetrahydrochloride, CGC-11093, in the colon adenocarcinoma cell line HCT1161.

    Science.gov (United States)

    Ignatenko, Natalia A; Yerushalmi, Hagit F; Watts, George S; Futscher, Bernard W; Stringer, David E; Marton, Laurence J; Gerner, Eugene W

    2006-12-01

    Polyamine analogs are known to inhibit tumorigenesis at least in part by mimicking some of the regulatory roles of natural polyamines. To begin the identification of those signaling pathways that are involved in differential cellular responses to the synthetic conformationally restricted polyamine analog CGC-11093, we conducted gene expression profiling, proteomic, and genome-wide DNA methylation and histone acetylation analyses of the HCT116 colon adenocarcinoma cell line after treatment with this analog. Gene expression analysis was performed using Affymetrix GeneChip human genome U133 Plus 2.0 arrays. Changes in protein expression were evaluated using 2D polyacrylamide gels followed by LCMS/MS. DNA methylation was measured using 6,800 element CpG island microarrays. Treatment of cells with CGC-11093 at concentrations ranging from 0.1 to 10 microM caused inhibition of cell growth and metabolic activity, but only minimally affected cell viability. Gene expression analysis showed concentration-dependent effects of CGC-11093 on the DNA/RNA binding transcription factor, cell cycle, signaling, transport, cytoskeletal/structural, and serine protease genes. Functional gene analysis revealed distinct expression patterns related to inhibition of cell cycle control, TGF beta signaling, proteasome and RNA polymerase pathways, upregulation of the aminoacyl-tRNA synthesis pathway, and perturbations in the MAPK and Wnt signaling pathways. Microarray results were validated for selected genes with real time RT PCR. Proteomics analysis showed correlative changes in the expression of proteins involved in the regulation of proteasome function (proteasome subunit Y) and tRNA synthesis. CGC-11093 treatment did not produce any detectable changes in DNA methylation or histone acetylation in cells. This study validates specific target pathways for a specific conformationally restricted polyamine analog and suggests the utility of combined gene and DNA methylation microarrays along with

  7. The study of optimal condition of SPIO labeling human lung adenocarcinoma cell line (SPC-A-1)

    Science.gov (United States)

    Yu, Ming-xi; Chen, Wen-li; Zhou, Quan; Xing, Da; Tang, Yong-hong

    2008-02-01

    Propose: To study the optimal concentration and time of incubation of human lung adenocarcinoma cell line (SPC-A-1) labeled with superparamagnetic iron oxide (SPIO) particles in vitro. Methods: Human lung adenocarcinoma cell line (SPC-A-1) was cultured with different concenration of SPIO and different time of incubation (labeled with media containing Fe-PLL: 25μg /mL, 100μg /mL, and 200 μg /mL, and for 30min, 90min, 180min. The phagocytosis of the cells was observed by laser scanning confocal microscopy (LSCM) to determine particle uptake and their distribution in cells. Results: Human lung adenocarcinoma cells(SPC-A-1) have taken up a large amount of SPIO particles within the first 3h. Conclusion: In this study, the concentration of iron with 25μg/ml SPIO and time of incubation for 30min is the optimal condition for labeling the SPC-A-1 with SPIO.

  8. Spatial distribution of B cells predicts prognosis in human pancreatic adenocarcinoma.

    Science.gov (United States)

    Castino, Giovanni Francesco; Cortese, Nina; Capretti, Giovanni; Serio, Simone; Di Caro, Giuseppe; Mineri, Rossana; Magrini, Elena; Grizzi, Fabio; Cappello, Paola; Novelli, Francesco; Spaggiari, Paola; Roncalli, Massimo; Ridolfi, Cristina; Gavazzi, Francesca; Zerbi, Alessandro; Allavena, Paola; Marchesi, Federica

    2016-04-01

    B-cell responses are emerging as critical regulators of cancer progression. In this study, we investigated the role of B lymphocytes in the microenvironment of human pancreatic ductal adenocarcinoma (PDAC), in a retrospective consecutive series of 104 PDAC patients and in PDAC preclinical models. Immunohistochemical analysis revealed that B cells occupy two histologically distinct compartments in human PDAC, either scatteringly infiltrating (CD20-TILs), or organized in tertiary lymphoid tissue (CD20-TLT). Only when retained within TLT, high density of B cells predicted longer survival (median survival 16.9 mo CD20-TLThi vs. 10.7 mo CD20-TLTlo; p = 0.0085). Presence of B cells within TLT associated to a germinal center (GC) immune signature, correlated with CD8-TIL infiltration, and empowered their favorable prognostic value. Immunotherapeutic vaccination of spontaneously developing PDAC (KrasG12D-Pdx1-Cre) mice with α-enolase (ENO1) induced formation of TLT with active GCs and correlated with increased recruitment of T lymphocytes, suggesting induction of TLT as a strategy to favor mobilization of immune cells in PDAC. In contrast, in an implanted tumor model devoid of TLT, depletion of B cells with an anti-CD20 antibody reinstated an antitumor immune response. Our results highlight B cells as an essential element of the microenvironment of PDAC and identify their spatial organization as a key regulator of their antitumor function. A mindfully evaluation of B cells in human PDAC could represent a powerful prognostic tool to identify patients with distinct clinical behaviors and responses to immunotherapeutic strategies.

  9. The Effects of Arsenic Trioxide on DNA Synthesis and Genotoxicity in Human Colon Cancer Cells

    OpenAIRE

    Christian Rogers; Tchounwou, Paul B.; Walker, Alice M.; Barbara Graham; Jacqueline J. Stevens

    2010-01-01

    Colon cancer is the third leading cause of cancer-related deaths worldwide. Recent studies in our laboratory have demonstrated that arsenic trioxide is cytotoxic in human colon cancer (HT-29), lung (A549) and breast (MCF-7) carcinoma cells. The purpose of the present study is to investigate the effects of arsenic trioxide on DNA synthesis and the possible genotoxic effects on human colon cancer cells. HT-29 cells were cultured according to standard protocol, followed by exposure to various do...

  10. Ultrastructure of interstitial cells in subserosa of human colon

    DEFF Research Database (Denmark)

    Rumessen, Jüri Johannes; Vanderwinden, Jean-Marie; Hansen, Alastair

    2013-01-01

    vesicles) were prominent. The IC-SS ultrastructure was different from that of FLC in the longitudinal layer, which had no caveolae and fewer intermediate filaments. Peg-and-socket junctions between IC-SS and between IC-SS and muscle cells were present, and IC-SS processes had close, selective appositions...... to muscle cells. Gap junctions were not observed. Small nerve bundles were abundant, but close contacts (......We studied the ultrastructure of interstitial cells in the subserosal/adventitial layer in human colon. An interstitial cell type with an ultrastructure intermediate between fibroblast-like cells (FLC) and interstitial cells of Cajal was identified (IC-SS). IC-SS had thin and flattened branching...

  11. VSV-MP gene therapy strategy inhibits tumor growth in nude mice model of human lung adenocarcinoma.

    Science.gov (United States)

    Jing, X-M; Wen, Y-J; Shi, W; Tang, Q-Q; Li, J; Chen, X-C

    2012-02-01

    Vesicular stomatitis virus (VSV) matrix protein (MP) can induce in vitro apoptosis of tumor cells in the absence of other viral components. Here, the antitumor activity of VSV-MP against lung adenocarcinoma was investigated in vivo. A pVAX-plasmid DNA encoding VSV-MP and control empty vectors (pVAX) were constructed and wrapped-up with liposome. A549 and Spc-A1 human lung adenocarcinoma cells were transfected with liposomal-VSV-MP (Lip-MP) or Lip-pVAX and then examined for cell viability or apoptosis using Hoechst/propidium iodide staining by flow cytometry, and further demonstrated by caspase/poly ADP-ribose polymerase (PARP) cleavage analysis. For the in vivo study, A549 and Spc-A1 lung carcinoma models in nude mice were established and randomly assigned into three groups to receive eight 2-weekly intravenous administrations of medium alone as control, Lip-pVAX or Lip-MP, respectively. Subsequently, Lip-MP significantly reduced tumor growth and prolonged the survival of tumor-bearing mice compared with Lip-pVAX and control agents (P<0.05), with much higher apoptosis index of both in vivo and in vitro tumor cells, respectively (P<0.05). In addition, in vivo antitumoral effect was associated with natural killer-(NK) cell congregation without evidence of toxicity. These observations suggest that systemically delivering Lip-MP has a specific dual antitumor activity in human lung adenocarcinoma by inducing apoptosis and possibly stimulating NK-cell responses, it may provide a clue for developing new therapeutic approaches against human lung adenocarcinoma.

  12. Staphylococcus aureus Colonization: Modulation of Host Immune Response and Impact on Human Vaccine Design

    Science.gov (United States)

    Brown, Aisling F.; Leech, John M.; Rogers, Thomas R.; McLoughlin, Rachel M.

    2014-01-01

    In apparent contrast to its invasive potential Staphylococcus aureus colonizes the anterior nares of 20–80% of the human population. The relationship between host and microbe appears particularly individualized and colonization status seems somehow predetermined. After decolonization, persistent carriers often become re-colonized with their prior S. aureus strain, whereas non-carriers resist experimental colonization. Efforts to identify factors facilitating colonization have thus far largely focused on the microorganism rather than on the human host. The host responds to S. aureus nasal colonization via local expression of anti-microbial peptides, lipids, and cytokines. Interplay with the co-existing microbiota also influences colonization and immune regulation. Transient or persistent S. aureus colonization induces specific systemic immune responses. Humoral responses are the most studied of these and little is known of cellular responses induced by colonization. Intriguingly, colonized patients who develop bacteremia may have a lower S. aureus-attributable mortality than their non-colonized counterparts. This could imply a staphylococcal-specific immune “priming” or immunomodulation occurring as a consequence of colonization and impacting on the outcome of infection. This has yet to be fully explored. An effective vaccine remains elusive. Anti-S. aureus vaccine strategies may need to drive both humoral and cellular immune responses to confer efficient protection. Understanding the influence of colonization on adaptive response is essential to intelligent vaccine design, and may determine the efficacy of vaccine-mediated immunity. Clinical trials should consider colonization status and the resulting impact of this on individual patient responses. We urgently need an increased appreciation of colonization and its modulation of host immunity. PMID:24409186

  13. BRAFV600E Efficient Transformation and Induction of Microsatellite Instability Versus KRASG12V Induction of Senescence Markers in Human Colon Cancer Cells

    Directory of Open Access Journals (Sweden)

    Eftychia Oikonomou

    2009-11-01

    Full Text Available In colorectal cancer, BRAF and KRAS oncogenes are mutated in about 15% and 35% respectively at approximately the same stage of the adenoma-carcinoma sequence. Since these two mutations rarely coexist, further analysis to dissect their function of transformation in colon cancer is required. Caco-2 human colon adenocarcinoma cells were stably transfected with BRAFV600E (Caco-BR cells or KRASG12V (Caco-K cells oncogenes. BRAFV600E is more efficient in transforming Caco-2 cells and altering their morphology. The dominant nature of BRAFV600E is evident by its ability to render Caco-2 cells tumorigenic in vivo all be it through selective extracellular signal-related kinase (ERK 2 phosphorylation and high levels of cyclin D1. As a consequence, the cell cycle distribution of parental cells is altered and microsatellite instability is introduced. Attenuated ERK activation observed correlated with KSR downregulation by BRAFV600E without further implications to signaling. Highly activated ERK in case of KRASG12V (Caco-K cells leads to mild transformation causing Caco-K cells to express premature senescence-related markers and acquire growth factor-dependent viability. Interestingly, BRAFWTgets equally activated by upstream KRAS mutations present in colon adenocarcinoma cells such as DLD-1 and SW620. Taken together, these results suggest that the two oncogenes have different transforming capability in colon cancer, although they both use the mitogen-activated protein (MAP kinase pathway to carry out their effect. In general, BRAFV600E presents greater potential in mediating tumorigenic effect as compared to KRASG12V both in vivo and in vitro. These findings may have implications in personalised diagnosis and targeted therapeutics.

  14. Growth Hormone differentially modulates chemoresistance in human endometrial adenocarcinoma cell lines.

    Science.gov (United States)

    Gentilin, Erica; Minoia, Mariella; Bondanelli, Marta; Tagliati, Federico; Degli Uberti, Ettore C; Zatelli, Maria Chiara

    2017-06-01

    Growth Hormone may influence neoplastic development of endometrial epithelium towards endometrial adenocarcinoma, which is one of the most occurring tumors in acromegalic patients. Since chemoresistance often develops in advanced endometrial adenocarcinoma, we investigated whether Growth Hormone might influence the development of chemoresistance to drugs routinely employed in endometrial adenocarcinoma treatment, such as Doxorubicin, Cisplatin, and Paclitaxel. Growth Hormone and Growth Hormone receptor expression was assessed by immunofluorescence in two endometrial adenocarcinoma cell lines, AN3 CA and HEC-1-A cells. Growth Hormone effects were assessed investigating cell viability, caspase3/7 activation, ERK1/2, and protein kinase C delta protein expression. AN3 CA and HEC-1-A cells display Growth Hormone and Growth Hormone receptor. Growth Hormone does not influence cell viability in both cells lines, but significantly reduces caspase 3/7 activation in AN3 CA cells, an effect blocked by a Growth Hormone receptor antagonist. Growth Hormone rescues AN3 CA cells from the inhibitory effects of Doxorubicin and Cisplatin on cell viability, while it has no effect on Paclitaxel. Growth Hormone does not influence the pro-apoptotic effects of Doxorubicin, but is capable of rescuing AN3 CA cells from the pro-apoptotic effects of Cisplatin. On the other hand, Growth Hormone did not influence the effects of Doxorubicin and Paclitaxel on HEC-1A cell viability. The protective action of Growth Hormone towards the effects of Doxorubicin may be mediated by ERK1/2 activation, while the pro-apoptotic effects of Cisplatin may be mediated by protein kinase C delta inhibition. All together our results indicate that Growth Hormone may differentially contribute to endometrial adenocarcinoma chemoresistance. This may provide new insights on novel therapies against endometrial adenocarcinoma chemoresistant aggressive tumors.

  15. Identification of crucial microRNAs and genes in hypoxia-induced human lung adenocarcinoma cells

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    Geng Y

    2016-07-01

    Full Text Available Ying Geng,1,* Lili Deng,2,* Dongju Su,1 Jinling Xiao,1 Dongjie Ge,3 Yongxia Bao,1 Hui Jing4 1Department of Respiratory, 2Department of Oncology, The Second Affiliated Hospital of Harbin Medical University, 3Department of Respiratory, The First Hospital of Harbin, 4Department of Emergency, The Second Affiliated Hospital of Harbin Medical University Harbin, Heilongjiang, People’s Republic of China *These authors contributed equally to this work Background: Variations of microRNA (miRNA expression profile in hypoxic lung cancer cells have not been studied so far. Therefore, using miRNA microarray technology, this study aimed to study the miRNA expression profile and investigate the potential crucial miRNAs and their target genes in hypoxia-induced human lung adenocarcinoma cells.Materials and methods: Based on miRNA microarray, miRNA expression profiling of hypoxia-induced lung adenocarcinoma A549 cells was obtained. After identification of differentially expressed miRNAs (DE-miRNAs in hypoxic cells, target genes of DE-miRNAs were predicted, and functional enrichment analysis of targets was conducted. Furthermore, the expression levels of DE-miRNAs and their target genes were validated by real-time quantitative polymerase chain reaction. In addition, using miRNA mimics, the effect of overexpressed DE-miRNAs on A549 cell behaviors (cell proliferation, cell cycle, and apoptosis was evaluated.Results: In total, 14 DE-miRNAs (nine upregulated miRNAs and five downregulated miRNAs were identified in hypoxic cells, compared with normoxic cells. Target genes of both upregulated and downregulated miRNAs were enriched in the functions such as chromatin modification, and pathways such as Wnt signaling pathway and transforming growth factor (TGF-β signaling pathway. The expression levels of several miRNAs and their target genes were confirmed, including hsa-miR-301b/FOXF2, hsa-miR-148b-3p/WNT10B, hsa-miR-769-5p/(SMAD2, ARID1A, and hsa-miR-622. Among them

  16. Induction of farnesoid X receptor signaling in germ-free mice colonized with a human microbiota.

    Science.gov (United States)

    Wahlström, Annika; Kovatcheva-Datchary, Petia; Ståhlman, Marcus; Khan, Muhammad-Tanweer; Bäckhed, Fredrik; Marschall, Hanns-Ulrich

    2017-02-01

    The gut microbiota influences the development and progression of metabolic diseases partly by metabolism of bile acids (BAs) and modified signaling through the farnesoid X receptor (FXR). In this study, we aimed to determine how the human gut microbiota metabolizes murine BAs and affects FXR signaling in colonized mice. We colonized germ-free mice with cecal content from a mouse donor or feces from a human donor and euthanized the mice after short-term (2 weeks) or long-term (15 weeks) colonization. We analyzed the gut microbiota and BA composition and expression of FXR target genes in ileum and liver. We found that cecal microbiota composition differed between mice colonized with mouse and human microbiota and was stable over time. Human and mouse microbiota reduced total BA levels similarly, but the humanized mice produced less secondary BAs. The human microbiota was able to reduce the levels of tauro-β-muricholic acid and induce expression of FXR target genes Fgf15 and Shp in ileum after long-term colonization. We show that a human microbiota can change BA composition and induce FXR signaling in colonized mice, but the levels of secondary BAs produced are lower than in mice colonized with a mouse microbiota. Copyright © 2017 by the American Society for Biochemistry and Molecular Biology, Inc.

  17. Constitutive expression of inducible nitric oxide synthase in the normal human colonic epithelium

    DEFF Research Database (Denmark)

    Perner, A; Andresen, Lars; Normark, M

    2002-01-01

    Inducible nitric oxide synthase (iNOS) in the human colon is considered expressed only in inflammatory states such as ulcerative or collagenous colitis. As subtle iNOS labelling was previously observed in some colonic mucosal biopsies from a heterogeneous group of controls with non-inflamed bowel...

  18. Flux analysis of the human proximal colon using anaerobic digestion model 1

    NARCIS (Netherlands)

    Motelica-Wagenaar, A.M.; Nauta, A.; van den Heuvel, E.G.H.M.; Kleerebezem, R.

    2014-01-01

    The colon can be regarded as an anaerobic digestive compartment within the gastro intestinal tract (GIT). An in silico model simulating the fluxes in the human proximal colon was developed on basis of the anaerobic digestion model 1 (ADM1), which is traditionally used to model waste conversion to

  19. Adenocarcinoma in situ and associated human papillomavirus type distribution observed in two clinical trials of a quadrivalent human papillomavirus vaccine

    DEFF Research Database (Denmark)

    Ault, Kevin A; Joura, Elmar A; Kjaer, Susanne K

    2011-01-01

    The primary objective of this report is to describe the detection of adenocarcinoma in situ (AIS) and associated human papillomavirus (HPV) type distribution that was observed in the context of two phase 3 clinical trials of a quadrivalent HPV6/11/16/18 vaccine. In this intention-to-treat analysis......, we include all women who had at least one follow-up visit postenrollment. Healthy women (17,622) aged 15-26 with no history of HPV disease and a lifetime number of less than five sex partners (average follow-up of 3.6 years) were randomized (1:1) to receive vaccine or placebo at day 1, months 2......, and 6. Women underwent colposcopy and biopsy according to a Papanicolaou triage algorithm. All tissue specimens were tested for 14 HPV types and were adjudicated by a pathology panel. During the trials, 22 women were diagnosed with AIS (six vaccine and 16 placebo). There were 25 AIS lesions in total...

  20. Muscarinic receptor agonists stimulate matrix metalloproteinase 1-dependent invasion of human colon cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Raufman, Jean-Pierre, E-mail: jraufman@medicine.umaryland.edu [Division of Gastroenterology and Hepatology, University of Maryland School of Medicine, Baltimore, MD (United States); Cheng, Kunrong; Saxena, Neeraj; Chahdi, Ahmed; Belo, Angelica; Khurana, Sandeep; Xie, Guofeng [Division of Gastroenterology and Hepatology, University of Maryland School of Medicine, Baltimore, MD (United States)

    2011-11-18

    Highlights: Black-Right-Pointing-Pointer Muscarinic receptor agonists stimulated robust human colon cancer cell invasion. Black-Right-Pointing-Pointer Anti-matrix metalloproteinase1 antibody pre-treatment blocks cell invasion. Black-Right-Pointing-Pointer Bile acids stimulate MMP1 expression, cell migration and MMP1-dependent invasion. -- Abstract: Mammalian matrix metalloproteinases (MMPs) which degrade extracellular matrix facilitate colon cancer cell invasion into the bloodstream and extra-colonic tissues; in particular, MMP1 expression correlates strongly with advanced colon cancer stage, hematogenous metastasis and poor prognosis. Likewise, muscarinic receptor signaling plays an important role in colon cancer; muscarinic receptors are over-expressed in colon cancer compared to normal colon epithelial cells. Muscarinic receptor activation stimulates proliferation, migration and invasion of human colon cancer cells. In mouse intestinal neoplasia models genetic ablation of muscarinic receptors attenuates carcinogenesis. In the present work, we sought to link these observations by showing that MMP1 expression and activation plays a mechanistic role in muscarinic receptor agonist-induced colon cancer cell invasion. We show that acetylcholine, which robustly increases MMP1 expression, stimulates invasion of HT29 and H508 human colon cancer cells into human umbilical vein endothelial cell monolayers - this was abolished by pre-incubation with atropine, a non-selective muscarinic receptor inhibitor, and by pre-incubation with anti-MMP1 neutralizing antibody. Similar results were obtained using a Matrigel chamber assay and deoxycholyltaurine (DCT), an amidated dihydroxy bile acid associated with colon neoplasia in animal models and humans, and previously shown to interact functionally with muscarinic receptors. DCT treatment of human colon cancer cells resulted in time-dependent, 10-fold increased MMP1 expression, and DCT-induced cell invasion was also blocked by pre

  1. Deep RNA sequencing analysis of readthrough gene fusions in human prostate adenocarcinoma and reference samples

    Directory of Open Access Journals (Sweden)

    Nacu Serban

    2011-01-01

    Full Text Available Abstract Background Readthrough fusions across adjacent genes in the genome, or transcription-induced chimeras (TICs, have been estimated using expressed sequence tag (EST libraries to involve 4-6% of all genes. Deep transcriptional sequencing (RNA-Seq now makes it possible to study the occurrence and expression levels of TICs in individual samples across the genome. Methods We performed single-end RNA-Seq on three human prostate adenocarcinoma samples and their corresponding normal tissues, as well as brain and universal reference samples. We developed two bioinformatics methods to specifically identify TIC events: a targeted alignment method using artificial exon-exon junctions within 200,000 bp from adjacent genes, and genomic alignment allowing splicing within individual reads. We performed further experimental verification and characterization of selected TIC and fusion events using quantitative RT-PCR and comparative genomic hybridization microarrays. Results Targeted alignment against artificial exon-exon junctions yielded 339 distinct TIC events, including 32 gene pairs with multiple isoforms. The false discovery rate was estimated to be 1.5%. Spliced alignment to the genome was less sensitive, finding only 18% of those found by targeted alignment in 33-nt reads and 59% of those in 50-nt reads. However, spliced alignment revealed 30 cases of TICs with intervening exons, in addition to distant inversions, scrambled genes, and translocations. Our findings increase the catalog of observed TIC gene pairs by 66%. We verified 6 of 6 predicted TICs in all prostate samples, and 2 of 5 predicted novel distant gene fusions, both private events among 54 prostate tumor samples tested. Expression of TICs correlates with that of the upstream gene, which can explain the prostate-specific pattern of some TIC events and the restriction of the SLC45A3-ELK4 e4-e2 TIC to ERG-negative prostate samples, as confirmed in 20 matched prostate tumor and normal

  2. Estimate of the global burden of cervical adenocarcinoma and potential impact of prophylactic human papillomavirus vaccination.

    Science.gov (United States)

    Pimenta, Jeanne M; Galindo, Claudia; Jenkins, David; Taylor, Sylvia M

    2013-11-21

    Data on the current burden of adenocarcinoma (ADC) and histology-specific human papillomavirus (HPV) type distribution are relevant to predict the future impact of prophylactic HPV vaccines. We estimate the proportion of ADC in invasive cervical cancer, the global number of cases of cervical ADC in 2015, the effect of cervical screening on ADC, the number of ADC cases attributable to high-risk HPV types -16, -18, -45, -31 and -33, and the potential impact of HPV vaccination using a variety of data sources including: GLOBOCAN 2008, Cancer Incidence in Five Continents (CI5) Volume IX, cervical screening data from the World Health Organization/Institut Català d'Oncologia Information Centre on HPV and cervical cancer, and published literature. ADC represents 9.4% of all ICC although its contribution varies greatly by country and region. The global crude incidence rate of cervical ADC in 2015 is estimated at 1.6 cases per 100,000 women, and the projected worldwide incidence of ADC in 2015 is 56,805 new cases. Current detection rates for HPV DNA in cervical ADC tend to range around 80-85%; the lower HPV detection rates in cervical ADC versus squamous cell carcinoma may be due to technical artefacts or to misdiagnosis of endometrial carcinoma as cervical ADC. Published data indicate that the five most common HPV types found in cervical ADC are HPV-16 (41.6%), -18 (38.7%), -45 (7.0%), -31 (2.2%) and -33 (2.1%), together comprising 92% of all HPV positive cases. Future projections using 2015 data, assuming 100% vaccine coverage and a true HPV causal relation of 100%, suggest that vaccines providing protection against HPV-16/18 may theoretically prevent 79% of new HPV-related ADC cases (44,702 cases annually) and vaccines additionally providing cross-protection against HPV-31/33/45 may prevent 89% of new HPV-related ADC cases (50,769 cases annually). It is predicted that the currently available HPV vaccines will be highly effective in preventing HPV-related cervical ADC.

  3. Expression of multiple forms of 3'-end variant CCK2 receptor mRNAs in human pancreatic adenocarcinomas

    Directory of Open Access Journals (Sweden)

    Monstein Hans-Jürg

    2011-04-01

    Full Text Available Abstract Background Two main types of receptors for gastrin and cholecystokinin (CCK have been cloned and identified. CCK1 (CCK-A receptors are expressed in the pancreas, the gallbladder, and parts of the brain, while CCK2 (CCK-B/gastrin receptors (CCK2R are expressed in gastric glands and in most of the brain. A splice variant of the CCK2R designated CCKRi4sv (CCK-C, which is constitutively expressed in human pancreatic cancer cells, has also been described. The purpose of the present investigation was to study CCK2R, CCK2i4svR, and gastrin mRNA expression in human pancreatic adenocarcinoma on the assumption that co-expression of CCK2R and gastrin or constitutive CCK2i4svR mRNA expression plays a pivotal role in the progression of pancreatic cancer. Findings PCR amplification using CCK2R specific primer-pairs, followed by ethidium-bromide stained agarose gel electrophoresis revealed the expression of wild-type CCK2R mRNA in 12 of 17 biopsy specimens. A CCK2R intron 4 specific nested PCR assay revealed that CCK2i4svR mRNA was expressed in only one of the biopsy specimen. The authenticity of PCR amplicons was confirmed by cloning of selected amplicons and DNA sequence analysis. Moreover, we found that hitherto undescribed multiple forms of 3'-end variant CCK2R mRNAs with various deletions in the retained intron 4 and exon 5, tentatively generating truncated proteins, were expressed in the pancreatic adenocarcinomas. Conclusion Cloning and DNA sequencing of selected amplicons revealed that CCK2R and multiple CCK2i4svR-like mRNAs are expressed in human pancreatic adenocarcinoma. The originally described CCK2i4svR mRNA was only expressed in one of 17 tumours and appears to be rarely expressed in pancreatic adenocarcinoma. We report that CCK2R- and gastrin mRNA co-expression may play a role in a portion, but not in all of these tumours, and that aberrant splicing takes places in these tissues generating multiple forms of 3'-end variant CCK2R mRNAs.

  4. Pretargeted 177Lu radioimmunotherapy of carcinoembryonic antigen-expressing human colonic tumors in mice

    National Research Council Canada - National Science Library

    Schoffelen, R; Graaf, W.T.A. van der; Franssen, G.M; Sharkey, R.M; Goldenberg, D.M; McBride, W.J; Rossi, E.A; Eek, A; Oyen, W.J.G; Boerman, O.C

    2010-01-01

    ... (CEA)-expressing human tumors. METHODS: To obtain the optimal therapeutic efficacy, several strategies were evaluated to increase the total amount of radioactivity targeted to subcutaneous LS174T colon cancer tumors in BALB/c nude mice...

  5. Human colon cancer HT-29 cell death responses to doxorubicin and Morus Alba leaves flavonoid extract.

    Science.gov (United States)

    Fallah, S; Karimi, A; Panahi, G; Gerayesh Nejad, S; Fadaei, R; Seifi, M

    2016-03-31

    The mechanistic basis for the biological properties of Morus alba flavonoid extract (MFE) and chemotherapy drug of doxorubicin on human colon cancer HT-29 cell line death are unknown. The effect of doxorubicin and flavonoid extract on colon cancer HT-29 cell line death and identification of APC gene expression and PARP concentration of HT-29 cell line were investigated. The results showed that flavonoid extract and doxorubicin induce a dose dependent cell death in HT-29 cell line. MFE and doxorubicin exert a cytotoxic effect on human colon cancer HT-29 cell line by probably promoting or induction of apoptosis.

  6. The Synergistic Effects of Low Dose Fluorouracil and TRAIL on TRAIL-Resistant Human Gastric Adenocarcinoma AGS Cells

    Directory of Open Access Journals (Sweden)

    Hong Zhu

    2013-01-01

    Full Text Available The TNF-related apoptosis-inducing ligand (TRAIL is a TNF family member which has been under intense focus because of its remarkable ability to induce apoptosis in malignant human cells while leaving normal cells unscathed. However, many cancer cells remain resistant to TRAIL. In this study, we had investigated the synergistic effects of low dose fluorouracil (5-Fu and TRAIL on TRAIL-resistant human gastric adenocarcinoma AGS cells and explored the potential mechanisms. Cell viability was analyzed by sulforhodamine B (SRB assay and the synergistic effects were evaluated by Jin’s formula and confirmed by both morphological changes under inverted microscope and flow cytometry. The expression of TRAIL-R1 (death receptor 4, DR4, TRAIL-R2 (DR5, TRAIL-R3 (decoy receptor, DcR1, TRAIL-R4 (DcR2, procaspase-3, procaspase-8, and procaspase-9 was detected by western blotting. Our results showed that there were significant synergistic effects of low dose 5-Fu and TRAIL on TRAIL-resistant AGS cells, and this effect was supposed to be mediated by decreasing DcR2 expression and increasing DR5 expression. The extrinsic and intrinsic apoptosis pathways were both activated. The data suggest that combined treatment of low dose 5-Fu and TRAIL can be an effective therapeutic approach for gastric adenocarcinoma.

  7. In vitro evaluation of the cellular effect of indium tin oxide nanoparticles using the human lung adenocarcinoma A549 cells.

    Science.gov (United States)

    Tabei, Yosuke; Sonoda, Akinari; Nakajima, Yoshihiro; Biju, Vasudevanpillai; Makita, Yoji; Yoshida, Yasukazu; Horie, Masanori

    2015-05-01

    Indium tin oxide (ITO) is widely used in liquid crystal displays (LCDs) or plasma and mobile phone displays. Elevated production and usage of ITO in such displays have led to increased concerns over the safety of industrial workers exposed to particulate aerosols produced during cutting, grinding and polishing of these materials. However, the cellular effects of ITO nanoparticles (NPs) are still unclear, although it has been reported that micro-scale ITO particles induce cytotoxicity. The aim of this study was to examine the potential of ITO NPs to induce cytotoxicity, oxidative stress, and DNA damage using human lung adenocarcinoma A549 cells. Here, stable dispersions of a medium containing ITO NPs were obtained using pre-adsorption and centrifugal fractionation methods, and the A549 cells were incubated in this medium. The ITO NPs showed low cytotoxic effects as shown by the WST-1 and LDH assays. Transmission electron microscopy observations showed the cellular uptake of ITO NPs. The ITO NPs increased the intracellular level of reactive oxygen species and the expression of the heme oxygenase 1 gene. Further, the results of alkaline comet assays showed that ITO NPs induced DNA damage. Thus, these results suggest that ITO NPs possess a genotoxic potential on human lung adenocarcinoma A549 cells.

  8. Yes-Associated Protein Expression Is Correlated to the Differentiation of Prostate Adenocarcinoma.

    Science.gov (United States)

    Noh, Myung-Giun; Kim, Sung Sun; Hwang, Eu Chang; Kwon, Dong Deuk; Choi, Chan

    2017-07-01

    Yes-associated protein (YAP) in the Hippo signaling pathway is a growth control pathway that regulates cell proliferation and stem cell functions. Abnormal regulation of YAP was reported in human cancers including liver, lung, breast, skin, colon, and ovarian cancer. However, the function of YAP is not known in prostate adenocarcinoma. The purpose of this study was to investigate the role of YAP in tumorigenesis, differentiation, and prognosis of prostate adenocarcinoma. The nuclear and cytoplasmic expression of YAP was examined in 188 cases of prostate adenocarcinoma using immunohistochemistry. YAP expression levels were evaluated in the nucleus and cytoplasm of the prostate adenocarcinoma and the adjacent normal prostate tissue. The presence of immunopositive tumor cells was evaluated and interpreted in comparison with the patients' clinicopathologic data. YAP expression levels were not significantly different between normal epithelial cells and prostate adenocarcinoma. However, YAP expression level was significantly higher in carcinomas with a high Gleason grades (8-10) than in carcinomas with a low Gleason grades (6-7) (p < .01). There was no statistical correlation between YAP expression and stage, age, prostate-specific antigen level, and tumor volume. Biochemical recurrence (BCR)-free survival was significantly lower in patients with high YAP expressing cancers (p = .02). However high YAP expression was not an independent prognostic factor for BCR in the Cox proportional hazards model. The results suggested that YAP is not associated with prostate adenocarcinoma development, but it may be associated with the differentiation of the adenocarcinoma. YAP was not associated with BCR.

  9. Magnetic Resonance Imaging Quantification of Fasted State Colonic Liquid Pockets in Healthy Humans.

    Science.gov (United States)

    Murray, Kathryn; Hoad, Caroline L; Mudie, Deanna M; Wright, Jeff; Heissam, Khaled; Abrehart, Nichola; Pritchard, Susan E; Al Atwah, Salem; Gowland, Penny A; Garnett, Martin C; Amidon, Gregory E; Spiller, Robin C; Amidon, Gordon L; Marciani, Luca

    2017-08-07

    The rate and extent of drug dissolution and absorption from solid oral dosage forms is highly dependent on the volume of liquid in the gastrointestinal tract (GIT). However, little is known about the time course of GIT liquid volumes after drinking a glass of water (8 oz), particularly in the colon, which is a targeted site for both locally and systemically acting drug products. Previous magnetic resonance imaging (MRI) studies offered novel insights on GIT liquid distribution in fasted humans in the stomach and small intestine, and showed that freely mobile liquid in the intestine collects in fairly distinct regions or "pockets". Based on this previous pilot data, we hypothesized that (1) it is possible to quantify the time course of the volume and number of liquid pockets in the undisturbed colon of fasted healthy humans following ingestion of 240 mL, using noninvasive MRI methods; (2) the amount of freely mobile water in the fasted human colon is of the order of only a few milliliters. Twelve healthy volunteers fasted overnight and underwent fasted abdominal MRI scans before drinking 240 mL (∼8 fluid ounces) of water. After ingesting the water they were scanned at frequent intervals for 2 h. The images were processed to quantify freely mobile water in the total and regional colon: ascending, transverse, and descending. The fasted colon contained (mean ± SEM) 11 ± 5 pockets of resting liquid with a total volume of 2 ± 1 mL (average). The colonic fluid peaked at 7 ± 4 mL 30 min after the water drink. This peak fluid was distributed in 17 ± 7 separate liquid pockets in the colon. The regional analysis showed that pockets of free fluid were found primarily in the ascending colon. The interindividual variability was very high; the subjects showed a range of number of colonic fluid pockets from 0 to 89 and total colonic freely mobile fluid volume from 0 to 49 mL. This is the first study measuring the time course of the number, regional location, and volume of

  10. A new stochastic and state space model of human colon cancer incorporating multiple pathways.

    Science.gov (United States)

    Tan, Wai Y; Yan, Xiao W

    2010-04-20

    Studies by molecular biologists and geneticists have shown that tumors of human colon cancer are developed from colon stem cells through two mechanisms: The chromosomal instability and the micro-satellite instability. The purpose of this paper is therefore to develop a new stochastic and state space model for carcinogenesis of human colon cancer incorporating these biological mechanisms. Based on recent biological studies, in this paper we have developed a state space model for human colon cancer. In this state space model, the stochastic system is represented by a stochastic model, involving 2 different pathways-the chromosomal instability pathway and the micro-satellite instability pathway; the observation, cancer incidence data, is represented by a statistical model. Based on this model we have developed a generalized Bayesian approach to estimate the parameters through the posterior modes of the parameters via Gibbs sampling procedures. We have applied this model to fit and analyze the SEER data of human colon cancers from NCI/NIH. Our results indicate that the model not only provides a logical avenue to incorporate biological information but also fits the data much better than other models including the 4-stage single pathway model. This model not only would provide more insights into human colon cancer but also would provide useful guidance for its prevention and control and for prediction of future cancer cases.

  11. Gene Therapy for Human Lung Adenocarcinoma Using a Suicide Gene Driven by a Lung-Specific Promoter Delivered by JC Virus-Like Particles.

    Directory of Open Access Journals (Sweden)

    Chun-Nun Chao

    Full Text Available Lung adenocarcinoma, the most commonly diagnosed type of lung cancer, has a poor prognosis even with combined surgery, chemotherapy, or molecular targeted therapies. Most patients are diagnosed with an in-operable advanced or metastatic disease, both pointing to the necessity of developing effective therapies for lung adenocarcinoma. Surfactant protein B (SP-B has been found to be overexpressed in lung adenocarcinoma. In addition, it has also been demonstrated that human lung adenocarcinoma cells are susceptible to the JC polyomavirus (JCPyV infection. Therefore, we designed that the JCPyV virus-like particle (VLP packaged with an SP-B promoter-driven thymidine kinase suicide gene (pSPB-tk for possible gene therapy of human lung adenocarcinoma. Plasmids expressing the GFP (pSPB-gfp or thymidine kinase gene (pSPB-tk under the control of the human SP-B promoter were constructed. The promoter's tissue specificity was tested by transfection of pSPB-gfp into A549, CH27, and H460 human lung carcinoma cells and non-lung cells. The JCPyV VLP's gene transfer efficiency and the selective cytotoxicity of pSPB-tk combined with ganciclovir (GCV were tested in vitro and in a xenograft mouse model. In the current study, we found that SP-B promoter-driven GFP was specifically expressed in human lung adenocarcinoma (A549 and large cell carcinoma (H460 cells. JCPyV VLPs were able to deliver a GFP reporter gene into A549 cells for expression. Selective cytotoxicity was observed in A549 but not non-lung cells that were transfected with pSPB-tk or infected with pSPB-tk-carrying JCPyV VLPs. In mice injected with pSPB-tk-carrying JCPyV VLPs through the tail vein and treated with ganciclovir (GCV, a potent 80% inhibition of growth of human lung adenocarcinoma nodules resulted. The JCPyV VLPs combined with the use of SP-B promoter demonstrates effectiveness as a potential gene therapy against human lung adenocarcinoma.

  12. Gene Therapy for Human Lung Adenocarcinoma Using a Suicide Gene Driven by a Lung-Specific Promoter Delivered by JC Virus-Like Particles.

    Science.gov (United States)

    Chao, Chun-Nun; Lin, Mien-Chun; Fang, Chiung-Yao; Chen, Pei-Lain; Chang, Deching; Shen, Cheng-Huang; Wang, Meilin

    2016-01-01

    Lung adenocarcinoma, the most commonly diagnosed type of lung cancer, has a poor prognosis even with combined surgery, chemotherapy, or molecular targeted therapies. Most patients are diagnosed with an in-operable advanced or metastatic disease, both pointing to the necessity of developing effective therapies for lung adenocarcinoma. Surfactant protein B (SP-B) has been found to be overexpressed in lung adenocarcinoma. In addition, it has also been demonstrated that human lung adenocarcinoma cells are susceptible to the JC polyomavirus (JCPyV) infection. Therefore, we designed that the JCPyV virus-like particle (VLP) packaged with an SP-B promoter-driven thymidine kinase suicide gene (pSPB-tk) for possible gene therapy of human lung adenocarcinoma. Plasmids expressing the GFP (pSPB-gfp) or thymidine kinase gene (pSPB-tk) under the control of the human SP-B promoter were constructed. The promoter's tissue specificity was tested by transfection of pSPB-gfp into A549, CH27, and H460 human lung carcinoma cells and non-lung cells. The JCPyV VLP's gene transfer efficiency and the selective cytotoxicity of pSPB-tk combined with ganciclovir (GCV) were tested in vitro and in a xenograft mouse model. In the current study, we found that SP-B promoter-driven GFP was specifically expressed in human lung adenocarcinoma (A549) and large cell carcinoma (H460) cells. JCPyV VLPs were able to deliver a GFP reporter gene into A549 cells for expression. Selective cytotoxicity was observed in A549 but not non-lung cells that were transfected with pSPB-tk or infected with pSPB-tk-carrying JCPyV VLPs. In mice injected with pSPB-tk-carrying JCPyV VLPs through the tail vein and treated with ganciclovir (GCV), a potent 80% inhibition of growth of human lung adenocarcinoma nodules resulted. The JCPyV VLPs combined with the use of SP-B promoter demonstrates effectiveness as a potential gene therapy against human lung adenocarcinoma.

  13. Identification of early microbial colonizers in human dental biofilm.

    Science.gov (United States)

    Li, J; Helmerhorst, E J; Leone, C W; Troxler, R F; Yaskell, T; Haffajee, A D; Socransky, S S; Oppenheim, F G

    2004-01-01

    To elucidate the first colonizers within in vivo dental biofilm and to establish potential population shifts that occur during the early phases of biofilm formation. A 'checkerboard' DNA-DNA hybridization assay was employed to identify 40 different bacterial strains. Dental biofilm samples were collected from 15 healthy subjects, 0, 2, 4 and 6 h after tooth cleaning and the composition of these samples was compared with that of whole saliva collected from the same individuals. The bacterial distribution in biofilm samples was distinct from that in saliva, confirming the selectivity of the adhesion process. In the very early stages, the predominant tooth colonizers were found to be Actinomyces species. The relative proportion of streptococci, in particular Streptococcus mitis and S. oralis, increased at the expense of Actinomyces species between 2 and 6 h while the absolute level of Actinomyces remained unaltered. Periodontal pathogens such as Tannerella forsythensis(Bacteroides forsythus), Porphyromonas gingivalis and Treponema denticola as well as Actinobacillus actinomycetemcomitans were present in extremely low levels at all the examined time intervals in this healthy group of subjects. The data provide a detailed insight into the bacterial population shifts occurring within the first few hours of biofilm formation and show that the early colonizers of the tooth surface predominantly consist of beneficial micro-organisms. The early colonizers of dental plaque are of great importance in the succession stages of biofilm formation and its overall effect on the oral health of the host.

  14. TfR2 expression in human colon carcinomas.

    Science.gov (United States)

    Calzolari, Alessia; Deaglio, Silvia; Maldi, Elena; Cassoni, Paola; Malavasi, Fabio; Testa, Ugo

    2009-01-01

    Different proteins regulate iron metabolism at the level of various tissues. Among these is a second transferrin receptor (TfR2) that seems to play a key role in the regulation of iron homeostasis. Although TfR2 expression in normal tissues is restricted at the level of the liver, we observed that TfR2 is frequently expressed in cancer cell lines. Taking advantage of this observation we investigated TfR2 expression in primary colon cancers, and showed that this receptor is expressed in about 26% of cases. TfR2 expression in colon cancer is not related to histological grade, but is preferentially associated with mucinous tumors. In colon cancer cell lines, TfR2 is localized in membrane lipid rafts, induces ERK1/ERK2 phosphorylation, when activated by its ligand transferring, and is preferentially expressed during S-M phases of the cell cycle. The presence of TfR2 on the membrane of colon cancer cells may contribute the growth advantage to these cells.

  15. Human nonsense-mediated RNA decay regulates EMT by targeting the TGF-ß signaling pathway in lung adenocarcinoma.

    Science.gov (United States)

    Cao, Lu; Qi, Lisha; Zhang, Lin; Song, Wangzhao; Yu, Yue; Xu, Cong; Li, Lingmei; Guo, Yuhong; Yang, Lingyi; Liu, Changxu; Huang, Qiujuan; Wang, Yalei; Sun, Baocun; Meng, Bin; Zhang, Bin; Cao, Wenfeng

    2017-09-10

    Nonsense-mediated mRNA decay (NMD) is a highly conserved pathway that selectively degrades aberrant RNA transcripts. In this study, we proved that NMD regulates the epithelial-mesenchymal transition (EMT) of lung adenocarcinoma (ADC). Moreover, we found that NMD core factor UP-frameshift 1 tends to be expressed at lower levels in human ADC tissues than in normal lung tissues, thereby raising the possibility that NMD may be downregulated to permit ADC oncogenesis. Our experiments in human ADC cell lines showed that downregulating NMD can promote EMT. Moreover, EMT can be inhibited by upregulating NMD. We tested the role of TGF-ß signaling and found that NMD influences EMT by targeting the TGF-ß signaling pathway. Our findings reveal that NMD is a potential tumor regulatory mechanism and may be a potential therapeutic target for ADC. Copyright © 2017 Elsevier B.V. All rights reserved.

  16. Secretomic Analysis Identifies Alpha-1 Antitrypsin (A1AT) as a Required Protein in Cancer Cell Migration, Invasion, and Pericellular Fibronectin Assembly for Facilitating Lung Colonization of Lung Adenocarcinoma Cells*

    Science.gov (United States)

    Chang, Ying-Hua; Lee, Shu-Hui; Liao, I-Chuang; Huang, Shin-Huei; Cheng, Hung-Chi; Liao, Pao-Chi

    2012-01-01

    Metastasis is a major obstacle that must be overcome for the successful treatment of lung cancer. Proteins secreted by cancer cells may facilitate the progression of metastasis, particularly within the phases of migration and invasion. To discover metastasis-promoting secretory proteins within cancer cells, we used the label-free quantitative proteomics approach and compared the secretomes from the lung adenocarcinoma cell lines CL1-0 and CL1-5, which exhibit low and high metastatic properties, respectively. By employing quantitative analyses, we identified 660 proteins, 68 of which were considered to be expressed at different levels between the two cell lines. High levels of A1AT were secreted by CL1-5, and the roles of A1AT in the influence of lung adenocarcinoma metastasis were investigated. Molecular and pathological confirmation demonstrated that altered expression of A1AT correlates with the metastatic potential of lung adenocarcinoma. The migration and invasion properties of CL1-5 cells were significantly diminished by reducing the expression and secretion of their A1AT proteins. Conversely, the migration and invasion properties of CL1-0 cells were significantly increased through the overexpression and secretion of A1AT proteins. Furthermore, the assembly levels of the metastasis-promoting pericellular fibronectin (FN1), which facilitates colonization of lung capillary endothelia by adhering to the cell surface receptor dipeptidyl peptidase IV (DPP IV), were higher on the surfaces of suspended CL1-5 cells than on those of the CL1-0 cells. This discovery reflects previous findings in breast cancer. In line with this finding, FN1 assembly and the lung colonization of suspended CL1-5 cells were inhibited when endogenous A1AT protein was knocked down using siRNA. The major thrust of this study is to demonstrate the effects of coupling the label-free proteomics strategy with the secretomes of cancer cells that differentially exhibit invasive and metastatic

  17. Galectin-1 is overexpressed in CD133+ human lung adenocarcinoma cells and promotes their growth and invasiveness

    Science.gov (United States)

    Zhou, Xuefeng; Li, Dan; Wang, Xianguo; Zhang, Bo; Zhu, Hua; Zhao, Jinping

    2015-01-01

    Previous studies demonstrated that a subpopulation of cancer cells, which are CD133 positive (CD133+) feature higher invasive and metastatic abilities, are called cancer stem cells (CSCs). By using tumor cells derived from patients with lung adenocarcinoma, we found that galectin-1 is highly overexpressed in the CD133+ cancer cells as compared to the normal cancer cells (CD133−) from the same patients. We overexpressed galectin-1 in CD133− cancer cells and downregulated it in CSCs. We found that overexpression of galectin-1 promoted invasiveness of CD133− cells, while knockdown of galectin-1 suppressed proliferation, colony formation and invasiveness of CSCs. Furthermore, tumor growth was significantly inhibited in CSCs xenografts with knockdown of galectin-1 as compared to CSCs treated with scramble siRNAs. Biochemical studies revealed that galectin-1 knockdown led to the suppression of COX-2/PGE2 and AKT/mTOR pathways, indicating galectin-1 might control the phenotypes of CSCs by regulating these signaling pathways. Finally, a retrospective study revealed that galectin-1 levels in blood circulation negatively correlates with overall survival and positively correlates with lymph node metastasis of the patients. Taken together, these findings suggested that galectin-1 plays a major role on the tumorigenesis and invasiveness of CD133+ cancer cells and might serve as a potential therapeutic target for treatment of human patients with lung adenocarcinoma. PMID:25605013

  18. Deficiency in the 15 kDa Selenoprotein Inhibits Human Colon Cancer Cell Growth

    Directory of Open Access Journals (Sweden)

    Ryuta Tobe

    2011-09-01

    Full Text Available Selenium is an essential micronutrient for humans and animals, and is thought to provide protection against some forms of cancer. These protective effects appear to be mediated, at least in part, through selenium-containing proteins (selenoproteins. Recent studies in a mouse colon cancer cell line have shown that the 15 kDa selenoprotein (Sep15 may also play a role in promoting colon cancer. The current study investigated whether the effects of reversing the cancer phenotype observed when Sep15 was removed in mouse colon cancer cells, were recapitulated in HCT116 and HT29 human colorectal carcinoma cells. Targeted down-regulation of Sep15 using RNAi technology in these human colon cancer cell lines resulted in similarly decreased growth under anchorage-dependent and anchorage-independent conditions. However, the magnitude of reduction in cell growth was much less than in the mouse colon cancer cell line investigated previously. Furthermore, changes in cell cycle distribution were observed, indicating a delayed release of Sep15 deficient cells from the G0/G1 phase after synchronization. The potential mechanism by which human colon cancer cells lacking Sep15 revert their cancer phenotype will need to be explored further.

  19. Induction of retinoic acid receptor β mediates growth inhibition in retinoid resistant human colon carcinoma cells

    OpenAIRE

    Nicke, B; Riecken, E; Rosewicz, S

    1999-01-01

    BACKGROUND—The molecular mechanisms underlying the differential sensitivity of human colon carcinoma cells to retinoid mediated growth inhibition are poorly understood.
AIM—To identify the intracellular mechanisms responsible for resistance against retinoid mediated growth inhibition in human colon carcinoma cells.
METHODS—Anchorage independent growth of the human colon carcinoma cell lines HT29 and LoVo was determined by a human tumour clonogenic assay. Retinoid receptor expression was evalu...

  20. Griffonia simplicifolia agglutinin-2-binding glycoprotein as a novel carbohydrate antigen of human colonic carcinoma.

    Science.gov (United States)

    Nakayama, J; Okano, A; Maeda, H; Miyachi, M; Ota, H; Katsuyama, T; Kanai, M

    1990-04-01

    Griffonia simplicifolia agglutinin-2-binding glycoprotein (GBG) in human colonic carcinoma was examined immunochemically and histochemically, GBG was extracted from colonic carcinoma as a serum-type glycoprotein of 160 kilodaltons. GBG was not identical with carcinoembryonic antigen (CEA), since its molecular weight and localization in tissue sections were different from those of CEA. The non-reducing terminals of GBG probably carry N-acetylglucosamine, but not blood group determinants. Furthermore, GBG was released by phosphatidylinositol-specific phospholipase C from cell membrane. GBG was suggested to be anchored to the membrane via linkage to a glycosyl-phosphatidylinositol molecule. Among colonic carcinoma-associated antigens, serum-type glycoproteins having N-acetylglucosamine at non-reducing terminals have not previously been reported. GBG is a novel carbohydrate antigen of human colonic carcinoma.

  1. Secreted Human Adipose Leptin Decreases Mitochondrial Respiration in HCT116 Colon Cancer Cells

    Science.gov (United States)

    Yehuda-Shnaidman, Einav; Nimri, Lili; Tarnovscki, Tanya; Kirshtein, Boris; Rudich, Assaf; Schwartz, Betty

    2013-01-01

    Obesity is a key risk factor for the development of colon cancer; however, the endocrine/paracrine/metabolic networks mediating this connection are poorly understood. Here we hypothesize that obesity results in secreted products from adipose tissue that induce malignancy-related metabolic alterations in colon cancer cells. Human HCT116 colon cancer cells, were exposed to conditioned media from cultured human adipose tissue fragments of obese vs. non-obese subjects. Oxygen consumption rate (OCR, mostly mitochondrial respiration) and extracellular acidification rate (ECAR, mostly lactate production via glycolysis) were examined vis-à-vis cell viability and expression of related genes and proteins. Our results show that conditioned media from obese (vs. non-obese) subjects decreased basal (40%, prespiration and function in HCT116 colon cancer cells, an effect that is at least partly mediated by leptin. These results highlight a putative novel mechanism for obesity-associated risk of gastrointestinal malignancies, and suggest potential new therapeutic avenues. PMID:24073224

  2. Galectin-8 expression decreases in cancer compared with normal and dysplastic human colon tissue and acts significantly on human colon cancer cell migration as a suppressor

    Science.gov (United States)

    Nagy, N; Bronckart, Y; Camby, I; Legendre, H; Lahm, H; Kaltner, H; Hadari, Y; Van Ham, P; Yeaton, P; Pector, J-C; Zick, Y; Salmon, I; Danguy, A; Kiss, R; Gabius, H-J

    2002-01-01

    Background and aims: Galectins are β-galactoside binding proteins. This ability may have a bearing on cell adhesion and migration/proliferation in human colon cancer cells. In addition to galectins-1 and -3 studied to date, other members of this family not investigated in detail may contribute to modulation of tumour cell features. This evident gap has prompted us to extend galectin analysis beyond the two prototypes. The present study deals with the quantitative determination of immunohistochemical expression of galectin-8 in normal, benign, and malignant human colon tissue samples and in four human colon cancer models (HCT-15, LoVo, CoLo201, and DLD-1) maintained both in vitro as permanent cell lines and in vivo as nude mice xenografts. The role of galectin-8 (and its neutralising antibody) in cell migration was investigated in HCT-15, LoVo, CoLo201, and DLD-1 cell lines. Methods: Immunohistochemical expression of galectin-8 and its overall ability to bind to sugar ligands (revealed glycohistochemically by means of biotinylated histochemically inert carrier bovine serum albumin with α- and β-d-galactose, α-d-glucose, and lactose derivatives as ligands) were quantitatively determined using computer assisted microscopy. The presence of galectin-8 mRNA in the four human colon cancer cell lines was examined by reverse transcriptase-polymerase chain reaction. In vitro, cellular localisation of exogenously added galectin-8 in the culture media of these colon cancer cells was visualised by fluorescence microscopy. In vitro galectin-8 mediated effects (and the influence of its neutralising antibody) on migration levels of living HCT-15, LoVo, CoLo201, and DLD-1 cells were quantitatively determined by computer assisted phase contrast microscopy. Results: A marked decrease in immunohistochemical expression of galectin-8 occurred with malignancy development in human colon tissue. Malignant colon tissue exhibited a significantly lower galectin-8 level than normal or

  3. Characterization of mammary adenocarcinomas in male rats after N-methyl-N-nitrosourea exposure--Potential for human male breast cancer model.

    Science.gov (United States)

    Yoshizawa, Katsuhiko; Yuki, Michiko; Kinoshita, Yuichi; Emoto, Yuko; Yuri, Takashi; Shikata, Nobuaki; Elmore, Susan A; Tsubura, Airo

    2016-05-01

    The frequency of breast cancer in men is extremely rare, reported to be less than 1% and there is currently no available animal model for male mammary tumors. We compared the characteristics of various immunohistochemical markers in N-methyl-N-nitrosourea (MNU)-induced mammary adenocarcinomas in male and female Crj:CD(SD)IGS rats including: estrogen receptor α (ER), progesterone receptor (PgR), androgen receptor (AR), receptor tyrosine-protein kinase erbB-2 (HER2), GATA binding protein 3 (GATA3), and proliferating cell nuclear antigen (PCNA). Female mammary adenocarcinomas were strongly positive in the nuclei of tumor cells for PCNA and ER (100%) with only 60% and 53% expressing PgR and GATA3, respectively. 100% of male adenocarcinomas also exhibited strongly positive expression in the nuclei of tumor cells for PCNA, with 25% expressing AR and only 8% showing positivity for ER. Male carcinomas did not express PgR or GATA3 and none of the tumors, male or female, were positive for HER2. Based on the observed ER and PgR positivity and HER2 negativity within these tumors, MNU-induced mammary adenocarcinomas in female rats appear to be hormonally dependent, similar to human luminal A type breast cancer. In contrast, MNU-induced mammary adenocarcinomas in male rats showed no reactivity for ER, PgR, HER2 or GATA3, suggesting no hormonal dependency. Both male and female adenocarcinomas showed high proliferating activity by PCNA immunohistochemistry. Based on our literature review, human male breast cancers are mainly dependent on ER and/or PgR, therefore the biological pathogenesis of MNU-induced male mammary cancer in rats may differ from that of male breast cancer in humans. Copyright © 2016 Elsevier GmbH. All rights reserved.

  4. Maslinic Acid, a Natural Triterpene, Induces a Death Receptor-Mediated Apoptotic Mechanism in Caco-2 p53-Deficient Colon Adenocarcinoma Cells.

    Directory of Open Access Journals (Sweden)

    Fernando J Reyes-Zurita

    Full Text Available Maslinic acid (MA is a natural triterpene present in high concentrations in the waxy skin of olives. We have previously reported that MA induces apoptotic cell death via the mitochondrial apoptotic pathway in HT29 colon cancer cells. Here, we show that MA induces apoptosis in Caco-2 colon cancer cells via the extrinsic apoptotic pathway in a dose-dependent manner. MA triggered a series of effects associated with apoptosis, including the cleavage of caspases -8 and -3, and increased the levels of t-Bid within a few hours of its addition to the culture medium. MA had no effect on the expression of the Bax protein, release of cytochrome-c or on the mitochondrial membrane potential. This suggests that MA triggered the extrinsic apoptotic pathway in this cell type, as opposed to the intrinsic pathway found in the HT29 colon-cancer cell line. Our results suggest that the apoptotic mechanism induced in Caco-2 may be different from that found in HT29 colon-cancer cells, and that in Caco-2 cells MA seems to work independently of p53. Natural antitumoral agents capable of activating both the extrinsic and intrinsic apoptotic pathways could be of great use in treating colon-cancer of whatever origin.

  5. The utility of Apc-mutant rats in modeling human colon cancer

    Directory of Open Access Journals (Sweden)

    Amy A. Irving

    2014-11-01

    Full Text Available Prior to the advent of genetic engineering in the mouse, the rat was the model of choice for investigating the etiology of cancer. Now, recent advances in the manipulation of the rat genome, combined with a growing recognition of the physiological differences between mice and rats, have reignited interest in the rat as a model of human cancer. Two recently developed rat models, the polyposis in the rat colon (Pirc and Kyoto Apc Delta (KAD strains, each carry mutations in the intestinal-cancer-associated adenomatous polyposis coli (Apc gene. In contrast to mouse models carrying Apc mutations, in which cancers develop mainly in the small intestine rather than in the colon and there is no gender bias, these rat models exhibit colonic predisposition and gender-specific susceptibility, as seen in human colon cancer. The rat also provides other experimental resources as a model organism that are not provided by the mouse: the structure of its chromosomes facilitates the analysis of genomic events, the size of its colon permits longitudinal analysis of tumor growth, and the size of biological samples from the animal facilitates multiplexed molecular analyses of the tumor and its host. Thus, the underlying biology and experimental resources of these rat models provide important avenues for investigation. We anticipate that advances in disease modeling in the rat will synergize with resources that are being developed in the mouse to provide a deeper understanding of human colon cancer.

  6. The utility of Apc-mutant rats in modeling human colon cancer

    Science.gov (United States)

    Irving, Amy A.; Yoshimi, Kazuto; Hart, Marcia L.; Parker, Taybor; Clipson, Linda; Ford, Madeline R.; Kuramoto, Takashi; Dove, William F.; Amos-Landgraf, James M.

    2014-01-01

    Prior to the advent of genetic engineering in the mouse, the rat was the model of choice for investigating the etiology of cancer. Now, recent advances in the manipulation of the rat genome, combined with a growing recognition of the physiological differences between mice and rats, have reignited interest in the rat as a model of human cancer. Two recently developed rat models, the polyposis in the rat colon (Pirc) and Kyoto Apc Delta (KAD) strains, each carry mutations in the intestinal-cancer-associated adenomatous polyposis coli (Apc) gene. In contrast to mouse models carrying Apc mutations, in which cancers develop mainly in the small intestine rather than in the colon and there is no gender bias, these rat models exhibit colonic predisposition and gender-specific susceptibility, as seen in human colon cancer. The rat also provides other experimental resources as a model organism that are not provided by the mouse: the structure of its chromosomes facilitates the analysis of genomic events, the size of its colon permits longitudinal analysis of tumor growth, and the size of biological samples from the animal facilitates multiplexed molecular analyses of the tumor and its host. Thus, the underlying biology and experimental resources of these rat models provide important avenues for investigation. We anticipate that advances in disease modeling in the rat will synergize with resources that are being developed in the mouse to provide a deeper understanding of human colon cancer. PMID:25288683

  7. Indoors forensic entomology: colonization of human remains in closed environments by specific species of sarcosaprophagous flies.

    Science.gov (United States)

    Pohjoismäki, Jaakko L O; Karhunen, Pekka J; Goebeler, Sirkka; Saukko, Pekka; Sääksjärvi, Ilari E

    2010-06-15

    Fly species that are commonly recovered on human corpses concealed in houses or other dwellings are often dependent on human created environments and might have special features in their biology that allow them to colonize indoor cadavers. In this study we describe nine typical cases involving forensically relevant flies on human remains found indoors in southern Finland. Eggs, larvae and puparia were reared to adult stage and determined to species. Of the five species found the most common were Lucilia sericata Meigen, Calliphora vicina Robineau-Desvoidy and Protophormia terraenovae Robineau-Desvoidy. The flesh fly Sarcophaga caerulescens Zetterstedt is reported for the first time to colonize human cadavers inside houses and a COI gene sequence based DNA barcode is provided for it to help facilitate identification in the future. Fly biology, colonization speed and the significance of indoors forensic entomological evidence are discussed. (c) 2010 Elsevier Ireland Ltd. All rights reserved.

  8. An Incidental Finding of Mucinous Colon Cancer by 18F-Choline PET/CT Determining a Change in Clinical Management of a Patient with Recurrent Prostate Adenocarcinoma

    Directory of Open Access Journals (Sweden)

    Carmelo Tuscano

    2014-01-01

    Full Text Available A 66-year-old-man underwent a PET/CT scan after a biochemical relapse for a prostate cancer previously treated with a laparoscopic surgical procedure which revealed a focal uptake in the posterior wall of sigmoid colon. The biopsy demonstrated a colon cancer with mucinous differentiation producing a shift in clinical priority. To the best of our knowledge this is the first report in the English literature describing the detection by 18F-choline PET/CT of a colorectal cancer with mucinous differentiation.

  9. Radiolabeling of bleomycin-glucuronide with (131)I and biodistribution studies using xenograft model of human colon tumor in Balb/C mice.

    Science.gov (United States)

    Demiroğlu, Hasan; Avcibaşi, Ugur; Ünak, Perihan; Müftüler, Fazilet Zümrüt Biber; İçhedef, Ç A; Gümüşer, Fikriye Gül; Sakarya, Serhan

    2012-08-01

    Bleomycin-glucuronide (BLMG) is the glucuronide conjugate of BLM. In the present study, BLMG was primarily enzymatically synthesized by using a microsome preparate separated from rat liver, labeled with (131)I by iodogen method with the aim of generating a radionuclide-labeled prodrug, and investigated its bioaffinities with tumor-bearing Balb/C mice. Quality control procedures were carried out using thin-layer radiochromatography and high-performance liquid chromatography. Tumor growing was carried out by following Caco-2 cell inoculation into mice. Radiolabeling yield was found to be about 65%. Results indicated that (131)I-labeled BLMG ((131)I-BLMG) was highly stable for 24 hours in human serum. Biodistribution studies were carried out with male Albino Wistar rats and colorectal adenocarcinoma tumor-bearing female Balb/C mice. The biodistribution results in rats showed high uptake in the prostate, the large intestine, and the spinal cord. In addition to this, scintigraphic results agreed with those of biodistributional studies. Xenography studies with tumor-bearing mice demonstrated that tumor uptakes of (131)I-BLM and (131)I-BLMG were high in the first 30 minutes postinjection. Tumor-bearing animal studies demonstrated that (131)I-BLMG was specially retained in colorectal adenocarcinoma with high tumor uptake. Therefore, (131)I-BLMG can be proven to be a promising imaging and therapeutic agent, especially for colon cancer in nuclear medical applications.

  10. Rapid effects of phytoestrogens on human colonic smooth muscle are mediated by oestrogen receptor beta.

    LENUS (Irish Health Repository)

    Hogan, A M

    2012-02-01

    Epidemiological studies have correlated consumption of dietary phytoestrogens with beneficial effects on colon, breast and prostate cancers. Genomic and non-genomic mechanisms are responsible for anti-carcinogenic effects but, until now, the effect on human colon was assumed to be passive and remote. No direct effect on human colonic smooth muscle has previously been described. Institutional research board approval was granted. Histologically normal colon was obtained from the proximal resection margin of colorectal carcinoma specimens. Circular smooth muscle strips were microdissected and suspended under 1g of tension in organ baths containing oxygenated Krebs solution at 37 degrees C. After an equilibration period, tissues were exposed to diarylpropionitrile (DPN) (ER beta agonist) and 1,3,5-tris(4-hydroxyphenyl)-4-propyl-1H-pyrazole (PPT) (ER alpha agonist) or to the synthetic phytoestrogen compounds genistein (n=8), daidzein (n=8), fisetin (n=8) and quercetin (n=8) in the presence or absence of fulvestrant (oestrogen receptor antagonist). Mechanism of action was investigated by inhibition of downstream pathways. The cholinergic agonist carbachol was used to induce contractile activity. Tension was recorded isometrically. Phytoestrogens inhibit carbachol-induced colonic contractility. In keeping with a non-genomic, rapid onset direct action, the effect was within minutes, reversible and similar to previously described actions of 17 beta oestradiol. No effect was seen in the presence of fulvestrant indicating receptor modulation. While the DPN exerted inhibitory effects, PPT did not. The effect appears to be reliant on a p38\\/mitogen activated protein kinase mediated induction of nitric oxide production in colonic smooth muscle. The present data set provides the first description of a direct effect of genistein, daidzein, fisetin and quercetin on human colonic smooth muscle. The presence of ER in colonic smooth muscle has been functionally proven and the beta

  11. Identifying candidate agents for lung adenocarcinoma by walking the human interactome

    Directory of Open Access Journals (Sweden)

    Sun Y

    2016-09-01

    Full Text Available Yajiao Sun,1 Ranran Zhang,2 Zhe Jiang,1 Rongyao Xia,1 Jingwen Zhang,1 Jing Liu,1 Fuhui Chen1 1Department of Respiratory, The Second Affiliated Hospital of Harbin Medical University, 2Department of Respiratory, Harbin First Hospital, Harbin, People’s Republic of China Abstract: Despite recent advances in therapeutic strategies for lung cancer, mortality is still increasing. Therefore, there is an urgent need to identify effective novel drugs. In the present study, we implement drug repositioning for lung adenocarcinoma (LUAD by a bioinformatics method followed by experimental validation. We first identified differentially expressed genes between LUAD tissues and nontumor tissues from RNA sequencing data obtained from The Cancer Genome Atlas database. Then, candidate small molecular drugs were ranked according to the effect of their targets on differentially expressed genes of LUAD by a random walk with restart algorithm in protein–protein interaction networks. Our method identified some potentially novel agents for LUAD besides those that had been previously reported (eg, hesperidin. Finally, we experimentally verified that atracurium, one of the potential agents, could induce A549 cells death in non-small-cell lung cancer-derived A549 cells by an MTT assay, acridine orange and ethidium bromide staining, and electron microscopy. Furthermore, Western blot assays demonstrated that atracurium upregulated the proapoptotic Bad and Bax proteins, downregulated the antiapoptotic p-Bad and Bcl-2 proteins, and enhanced caspase-3 activity. It could also reduce the expression of p53 and p21Cip1/Waf1 in A549 cells. In brief, the candidate agents identified by our approach may provide greater insights into improving the therapeutic status of LUAD. Keywords: lung adenocarcinoma, drug repositioning, bioinformatics, protein–protein interaction network, atracurium

  12. Rhein induces apoptosis of HCT-116 human colon cancer cells via ...

    African Journals Online (AJOL)

    Rhein, a major compound in rhubarb, has been found to have anti-tumor properties in many human cancer cells. However, the details about rhein suppressing the growth of human colon cancer cells remained elusive. In this paper, we explored the potential of rhein as a chemotherapeutic agent on HCT- 116 cells and ...

  13. An iPSC Line from Human Pancreatic Ductal Adenocarcinoma Undergoes Early to Invasive Stages of Pancreatic Cancer Progression

    Directory of Open Access Journals (Sweden)

    Jungsun Kim

    2013-06-01

    Full Text Available Pancreatic ductal adenocarcinoma (PDAC carries a dismal prognosis and lacks a human cell model of early disease progression. When human PDAC cells are injected into immunodeficient mice, they generate advanced-stage cancer. We hypothesized that if human PDAC cells were converted to pluripotency and then allowed to differentiate back into pancreatic tissue, they might undergo early stages of cancer. Although most induced pluripotent stem cell (iPSC lines were not of the expected cancer genotype, one PDAC line, 10–22 cells, when injected into immunodeficient mice, generated pancreatic intraepithelial neoplasia (PanIN precursors to PDAC that progressed to the invasive stage. The PanIN-like cells secrete or release proteins from many genes that are known to be expressed in human pancreatic cancer progression and that predicted an HNF4α network in intermediate-stage lesions. Thus, rare events allow iPSC technology to provide a live human cell model of early pancreatic cancer and insights into disease progression.

  14. A robust method for evaluation of NANC transmission in human sigmoid colon muscle in vitro.

    Science.gov (United States)

    Tavares, I A; Rennie, J A

    2001-01-01

    Human tissues are notoriously difficult to work with, giving results that are quantitatively variable within and between studies. Hence, previous investigations of nonadrenergic, noncholinergic (NANC) relaxation in human colon muscle report both partial and complete inhibitions of the NANC response by specific competitive inhibitors of nitric oxide (NO) production. We have established a robust and reproducible model to examine the contribution of NO during NANC relaxation assay in human sigmoid colon muscle strips. Complete control curves to long-train, stepwise, frequency-dependent, continuous electrical field stimulation (EFS) relaxation using vertical platinum electrodes connected to a biphasic pulse train stimulator generated NANC responses in fresh human sigmoid colon circular muscle strips set up in Bennett baths. A second complete curve was generated on the same strip in the presence of specific drugs to determine the contribution of NO to NANC relaxation. Responses to NO were also generated in muscle strips. Results were fitted to the Hill equation. The first and second frequency-response curves without test drugs could be fitted to the Hill equation, resulting in similar midpoint locations ([f](50)), maximal asymptotes (alpha), and midpoint slope (n) parameters. L-N(G)-nitro-arginine (L-NOARG), TTX, and haemoglobin produced a tonic contraction in the muscle strips. NANC relaxations to EFS were inhibited by L-NOARG (30-37%), TTX (56-62%), and haemoglobin (48-90%). NO relaxations were concentration dependently inhibited by haemoglobin. Haemoglobin was equipotent in mediating tonic contraction and inhibiting NO relaxation. We established reproducible assays for human colon muscle strips by the generation of two complete dose-response curves to long-train EFS, thus enabling a "within-preparations" study. The results suggest that NO contributes but is not the sole mediator of relaxations to long-train EFS in human sigmoid colon muscle. Moreover, a basal

  15. Urachal Adenocarcinoma

    African Journals Online (AJOL)

    Cancer. 1991; 67:2165-72. 6. Thali-Schwab CM, Woodward PJ, Wagner BJ. Computed tomographic appearance of urachal adenocarcinomas: review of 25 cases. Eur Radiol. 2005; 15:79-84. 7. Wong-You-Cheong JJ, Woodward PJ, Manning. MA, et al. Neoplasms of the urinary bladder: radiologic-pathologic correlation.

  16. Study on Invasion of Artesunate on Inhibiting Human Colon Cancer Cell SW620

    Directory of Open Access Journals (Sweden)

    Yu Fan

    2013-09-01

    Full Text Available Objective: To observe the invasive effect of Chinese extraction artesunate on human colon cancer cell SW620 and explore its possible mechanisms. Methods: Colon cancer cell SW620 was managed by different concentrations of artesunate, and soft agar colony-cultivating trial was applied to detect anchorage independent proliferation of cancer cells, Boyden chamber model method to detect the invasive capability of cancer cells and Western blot method to detect the change of intercellular adhesion molecule-1 (ICAM-1 proteins. Results: Artesunate can effectively inhibit malignant proliferation and invasive capability of colon cancer cell SW620, and was dose-dependent (P < 0.01. Artesunate can effectively inhibit the expression of cancer cell ICAM-1 gene proteins, and was time- and concentration-dependant (P <0.01. Conclusion: Artesunate can significantly inhibit the invasion of colon cancer cell SW620, which can be related to down-regulation of ICAM-1 protein level.

  17. Characterization of AQPs in Mouse, Rat, and Human Colon and Their Selective Regulation by Bile Acids

    DEFF Research Database (Denmark)

    Yde, Jonathan; Keely, Stephen; Wu, Qi

    2016-01-01

    In normal individuals, the epithelium of the colon absorbs 1.5-2 l of water a day to generate dehydrated feces. However, in the condition of bile acid malabsorption (BAM), an excess of bile acids in the colon results in diarrhea. Several studies have attempted to address the mechanisms contributing...... to BAM induced by various bile acids. However, none have addressed a potential dysregulation of aquaporin (AQP) water channels, which are responsible for the majority of transcellular water transport in epithelial cells, as a contributing factor to the onset of diarrhea and the pathogenesis of BAM....... In this study, we aimed to systematically analyze the expression of AQPs in colonic epithelia from rat, mouse, and human and determine whether their expression is altered in a rat model of BAM. Mass spectrometry-based proteomics, RT-PCR, and western blotting identified various AQPs in isolated colonic...

  18. Flagellin Induces β-Defensin 2 in Human Colonic Ex vivo Infection with Enterohemorrhagic Escherichia coli.

    Science.gov (United States)

    Lewis, Steven B; Prior, Alison; Ellis, Samuel J; Cook, Vivienne; Chan, Simon S M; Gelson, William; Schüller, Stephanie

    2016-01-01

    Enterohemorrhagic E.coli (EHEC) is an important foodborne pathogen in the developed world and can cause life-threatening disease particularly in children. EHEC persists in the human gut by adhering intimately to colonic epithelium and forming characteristic attaching/effacing lesions. In this study, we investigated the innate immune response to EHEC infection with particular focus on antimicrobial peptide and protein expression by colonic epithelium. Using a novel human colonic biopsy model and polarized T84 colon carcinoma cells, we found that EHEC infection induced expression of human β-defensin 2 (hBD2), whereas hBD1, hBD3, LL-37, and lysozyme remained unchanged. Infection with specific EHEC deletion mutants demonstrated that this was dependent on flagellin, and apical exposure to purified flagellin was sufficient to stimulate hBD2 and also interleukin (IL)-8 expression ex vivo and in vitro. Flagellin-mediated hBD2 induction was significantly reduced by inhibitors of NF-κB, MAP kinase p38 and JNK but not ERK1/2. Interestingly, IL-8 secretion by polarized T84 cells was vectorial depending on the side of stimulation, and apical exposure to EHEC or flagellin resulted in apical IL-8 release. Our results demonstrate that EHEC only induces a modest immune response in human colonic epithelium characterized by flagellin-dependent induction of hBD2 and low levels of IL-8.

  19. Expression and Prognostic Significance of Human Epidermal Growth Factor Receptors 1, 2 and 3 in Periampullary Adenocarcinoma.

    Directory of Open Access Journals (Sweden)

    Jacob Elebro

    Full Text Available Periampullary adenocarcinoma, including pancreatic cancer, is a heterogeneous group of tumours with dismal prognosis, for which there is an urgent need to identify novel treatment strategies. The human epithelial growth factor receptors EGFR, HER2 and HER3 have been studied in several tumour types, and HER-targeting drugs have a beneficial effect on survival in selected types of cancer. However, these effects have not been evident in pancreatic cancer, and remain unexplored in other types of periampullary cancer. The prognostic impact of HER-expression in these cancers also remains unclear. The aim of this study was therefore to examine the expression and prognostic value of EGFR, HER2 and HER3 in periampullary cancer, with particular reference to histological subtype. To this end, protein expression of EGFR, HER2 and HER3, and HER2 gene amplification was assessed by immunohistochemistry and silver in situ hybridization, respectively, on tissue microarrays with tumours from 175 periampullary adenocarcinomas, with follow-up data on recurrence-free survival (RFS and overall survival (OS for up to 5 years. EGFR expression was similar in pancreatobiliary (PB and intestinal (I type tumours, but high HER2 and HER3 expression was significantly more common in I-type tumours. In PB-type cases receiving adjuvant gemcitabine, but not in untreated cases, high EGFR expression was significantly associated with a shorter OS and RFS, with a significant treatment interaction in relation to OS (pinteraction = 0.042. In I-type cases, high EGFR expression was associated with a shorter OS and RFS in univariable, but not in multivariable, analysis. High HER3 expression was associated with a prolonged RFS in univariable, but not in multivariable, analysis. Neither HER2 protein expression nor gene amplification was prognostic. The finding of a potential interaction between the expression of EGFR and response to adjuvant chemotherapy in PB-type tumours needs validation

  20. Cannabidiol and palmitoylethanolamide are anti-inflammatory in the acutely inflamed human colon.

    Science.gov (United States)

    Couch, Daniel G; Tasker, Chris; Theophilidou, Elena; Lund, Jonathan N; O'Sullivan, Saoirse E

    2017-11-01

    We sought to quantify the anti-inflammatory effects of two cannabinoid drugs, cannabidiol (CBD) and palmitoylethanolamide (PEA), in cultured cell lines and compared this effect with experimentally inflamed explant human colonic tissue. These effects were explored in acutely and chronically inflamed colon, using inflammatory bowel disease and appendicitis explants. Caco-2 cells and human colonic explants collected from elective bowel cancer, inflammatory bowel disease (IBD) or acute appendicitis resections, and were treated with the following drug treatments: vehicle, an inflammatory protocol of interferon γ (IFNγ) and tumour necrosis factor α (TNFα; 10 ng/ml), inflammation and PEA (10 µM), inflammation and CBD (10 µM), and PEA or CBD alone, CBD or vehicle were added simultaneously with IFNγ. Nine intracellular signalling phosphoproteins were determined by multiplex. Inflammatory cytokine secretion was determined using ELISA. Receptor mechanisms were investigated using antagonists for CB1, CB2, PPARα, PPARγ, TRPV1 and GPR55. IFNγ and TNFα treatment increased phosphoprotein and cytokine levels in Caco-2 cultures and colonic explants. Phosphoprotein levels were significantly reduced by PEA or CBD in Caco-2 cultures and colonic explants. CBD and PEA prevented increases in cytokine production in explant colon, but not in Caco-2 cells. CBD effects were blocked by the CB2 antagonist AM630 and TRPV1 antagonist SB366791. PEA effects were blocked by the PPARα antagonist GW6471. PEA and CBD were anti-inflammatory in IBD and appendicitis explants. PEA and CBD are anti-inflammatory in the human colon. This effect is not seen in cultured epithelial cells. Appropriately sized clinical trials should assess their efficacy. © 2017 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

  1. Terahertz pulsed imaging of freshly excised human colonic tissues

    Energy Technology Data Exchange (ETDEWEB)

    Reid, Caroline B; Gibson, Adam P [Department of Medical Physics and Bioengineering, University College London, London, WC1E 6BT (United Kingdom); Fitzgerald, Anthony; Wallace, Vincent P [School of Physics, University of Western Australia, Crawley 6009 (Australia); Reese, George; Tekkis, Paris [Division of Surgery, Chelsea and Westminster Campus, Imperial College London, London (United Kingdom); Goldin, Robert [Centre for Pathology, Imperial College London, St Mary' s Campus, London (United Kingdom); O' Kelly, P S [TeraView Ltd, Platinum Building, St John' s Innovation Park, Cowley Road, Cambridge, CB4 0WS (United Kingdom); Pickwell-MacPherson, Emma, E-mail: c.reid@medphys.ucl.ac.uk [Department of Electronic Engineering, Chinese University of Hong Kong, Shatin, NT (Hong Kong)

    2011-07-21

    We present the results from a feasibility study which measures properties in the terahertz frequency range of excised cancerous, dysplastic and healthy colonic tissues from 30 patients. We compare their absorption and refractive index spectra to identify trends which may enable different tissue types to be distinguished. In addition, we present statistical models based on variations between up to 17 parameters calculated from the reflected time and frequency domain signals of all the measured tissues. These models produce a sensitivity of 82% and a specificity of 77% in distinguishing between healthy and all diseased tissues and a sensitivity of 89% and a specificity of 71% in distinguishing between dysplastic and healthy tissues. The contrast between the tissue types was supported by histological staining studies which showed an increased vascularity in regions of increased terahertz absorption.

  2. Effect of Inulin on Proteome Changes Induced by Pathogenic Lipopolysaccharide in Human Colon.

    Science.gov (United States)

    Guarino, Michele Pier Luca; Altomare, Annamaria; Barera, Simone; Locato, Vittoria; Cocca, Silvia; Franchin, Cinzia; Arrigoni, Giorgio; Vannini, Candida; Grossi, Sarah; Campomenosi, Paola; Pasqualetti, Valentina; Bracale, Marcella; Alloni, Rossana; De Gara, Laura; Cicala, Michele

    2017-01-01

    In the present study, the protective role of inulin against lipopolysaccharide (LPS)-induced oxidative stress was evaluated on human colonic mucosa using a proteomic approach. Human colonic mucosa and submucosa were sealed between two chambers, with the luminal side facing upwards and overlaid with Krebs (control), LPS or LPS+ inulin IQ solution. The solutions on the submucosal side (undernatants) were collected following 30 min of mucosal exposure. iTRAQ based analysis was used to analyze the total soluble proteomes from human colonic mucosa and submucosa treated with different undernatants. Human colonic muscle strips were exposed to the undernatants to evaluate the response to acetylcholine. Inulin exposure was able to counteract, in human colonic mucosa, the LPS-dependent alteration of some proteins involved in the intestinal contraction (myosin light chain kinase (MLCK), myosin regulatory subunit (MYL)), to reduce the up-regulation of two proteins involved in the radical-mediated oxidative stress (the DNA-apurinic or apyrimidinic site) lyase) APEX1 and the T-complex protein 1 subunit eta (CCT7) and to entail a higher level of some detoxification enzymes (the metallothionein-2 MT2A, the glutathione-S-transferase K GSTk, and two UDP- glucuronosyltransferases UGT2B4, UGT2B17). Inulin exposure was also able to prevent the LPS-dependent intestinal muscle strips contraction impairment and the mucosa glutathione level alterations. Exposure of colonic mucosa to inulin seems to prevent LPS-induced alteration in expression of some key proteins, which promote intestinal motility and inflammation, reducing the radical-mediated oxidative stress.

  3. Antiproliferative activity of New Zealand propolis and phenolic compounds vs human colorectal adenocarcinoma cells.

    Science.gov (United States)

    Catchpole, Owen; Mitchell, Kevin; Bloor, Stephen; Davis, Paul; Suddes, Amanda

    2015-10-01

    New Zealand propolis is a "European" type propolis obtained by honey bees mainly from exudates of poplar. European type propolis is known to have anti-inflammatory and anti-cancer properties and this activity has been attributed to some of the main constituents such as chrysin and CAPE (caffeic acid phenethyl ester). As part of our studies on how New Zealand propolis might benefit gastro-intestinal health, we carried out in vitro bioactivity-guided fractionation of "Bio30™" propolis using both anti-inflammatory (TNF-α, COX-1, COX-2) and anti-colon cancer (DLD-1 colon cancer cell viability) assays; and determined the phenolic compounds responsible for the activity. The New Zealand wax-free Bio30™ propolis tincture solids had very high levels of the dihydroflavonoids pinocembrin and pinobanksin-3-O-acetate, and high levels of the dimethylallyl, benzyl and 3-methyl-3-butenyl caffeates relative to CAPE. The DLD-1 assays identified strong anti-proliferative activity associated with these components as well as chrysin, galangin and CAPE and a number of lesser known or lower concentration compounds including benzyl ferulate, benzyl isoferulate, pinostrobin, 5-phenylpenta-2,4-dienoic acid and tectochrysin. The phenolic compounds pinocembrin, pinobanksin-3-O-acetate, tectochrysin, dimethylallyl caffeate, 3-methyl-3-butenyl caffeate, benzyl ferulate and benzyl isoferulate also showed good broad spectrum activity in anti-proliferative assays against three other gastro-intestinal cancer cell lines; HCT-116 colon carcinoma, KYSE-30 oesophageal squamous cancer, and NCI-N87 gastric carcinoma. Activity is also observed in anti-inflammatory assays although it appears to be limited to one of the first cytokines in the inflammatory cascade, TNF-α. Copyright © 2015 Elsevier B.V. All rights reserved.

  4. Mechanism of arctigenin-mediated specific cytotoxicity against human lung adenocarcinoma cell lines.

    Science.gov (United States)

    Susanti, Siti; Iwasaki, Hironori; Inafuku, Masashi; Taira, Naoyuki; Oku, Hirosuke

    2013-12-15

    The lignan arctigenin (ARG) from the herb Arctium lappa L. possesses anti-cancer activity, however the mechanism of action of ARG has been found to vary among tissues and types of cancer cells. The current study aims to gain insight into the ARG mediated mechanism of action involved in inhibiting proliferation and inducing apoptosis in lung adenocarcinoma cells. This study also delineates the cancer cell specificity of ARG by comparison with its effects on various normal cell lines. ARG selectively arrested the proliferation of cancer cells at the G0/G1 phase through the down-regulation of NPAT protein expression. This down-regulation occurred via the suppression of either cyclin E/CDK2 or cyclin H/CDK7, while apoptosis was induced through the modulation of the Akt-1-related signaling pathway. Furthermore, a GSH synthase inhibitor specifically enhanced the cytotoxicity of ARG against cancer cells, suggesting that the intracellular GSH content was another factor influencing the susceptibility of cancer cells to ARG. These findings suggest that specific cytotoxicity of ARG against lung cancer cells was explained by its selective modulation of the expression of NPAT, which is involved in histone biosynthesis. The cytotoxicity of ARG appeared to be dependent on the intracellular GSH level. Copyright © 2013 Elsevier GmbH. All rights reserved.

  5. Dihydroartemisinin (DHA induces caspase-3-dependent apoptosis in human lung adenocarcinoma ASTC-a-1 cells

    Directory of Open Access Journals (Sweden)

    Sun Lei

    2009-02-01

    Full Text Available Abstract Background Dihydroartemisinin (DHA, a semi-synthetic derivative of artemisinin, isolated from the traditional Chinese herb Artemisia annua, is recommended as the first-line anti-malarial drug with low toxicity. DHA has been shown to possess promising anticancer activities and induce cancer cell death through apoptotic pathways, although the molecular mechanisms are not well understood. Methods In this study, cell counting kit (CCK-8 assay was employed to evaluate the survival of DHA-treated ASTC-a-1 cells. The induction of apoptosis was detected by Hoechst 33258 and PI staining as well as flow cytometry analysis. Collapse of mitochondrial transmembrane potential (ΔΨm was measured by dynamic detection under a laser scanning confocal microscope and flow cytometry analysis using Rhodamine123. Caspase-3 activities measured with or without Z-VAD-fmk (a broad spectrum caspase inhibitor pretreatment by FRET techniques, caspase-3 activity measurement, and western blotting analysis. Results Our results indicated that DHA induced apoptotic cell death in a dose- and time-dependent manner, which was accompanied by mitochondrial morphology changes, the loss of ΔΨm and the activation of caspase-3. Conclusion These results show for the first time that DHA can inhibit proliferation and induce apoptosis via caspase-3-dependent mitochondrial death pathway in ASTC-a-1 cells. Our work may provide evidence for further studies of DHA as a possible anticancer drug in the clinical treatment of lung adenocarcinoma.

  6. On the relationship between sialomucin and sulfomucin expression and hydrogenotrophic microbes in the human colonic mucosa.

    Directory of Open Access Journals (Sweden)

    Jennifer A Croix

    Full Text Available The colonic mucus layer is comprised primarily of acidomucins, which provide viscous properties and can be broadly classified into sialomucins or sulfomucins based on the presence of terminating sialic acid or sulfate groups. Differences in acidomucin chemotypes have been observed in diseases such as colorectal cancer and inflammatory bowel disease, and variation in sialo- and sulfomucin content may influence microbial colonization. For example, sulfate derived from sulfomucin degradation may promote the colonization of sulfate-reducing bacteria (SRB, which through sulfate respiration generate the genotoxic gas hydrogen sulfide. Here, paired biopsies from right colon, left colon, and rectum of 20 subjects undergoing routine screening colonoscopies were collected to enable parallel histochemical and microbiological studies. Goblet cell sialo- and sulfomucins in each biopsy were distinguished histochemically and quantified. Quantitative PCR and multivariate analyses were used to examine the abundance of hydrogenotrophic microbial groups and SRB genera relative to acidomucin profiles. Regional variation was observed in sialomucins and sulfomucins with the greatest abundance of each found in the rectum. Mucin composition did not appear to influence the abundance of SRB or other hydrogenotrophic microbiota but correlated with the composition of different SRB genera. A higher sulfomucin proportion correlated with higher quantities of Desulfobacter, Desulfobulbus and Desulfotomaculum, relative to the predominant Desulfovibrio genus. Thus, acidomucin composition may influence bacterial sulfate respiration in the human colon, which may in turn impact mucosal homeostasis. These results stress the need to consider mucus characteristics in the context of studies of the microbiome that target intestinal diseases.

  7. Antitumor activity of a Trans-thiosemicarbazone schiff base palladium (II) complex on human gastric adenocarcinoma cells.

    Science.gov (United States)

    Zhang, Bingchang; Luo, Haiqing; Xu, Qinjuan; Lin, Lirong; Zhang, Bing

    2017-02-21

    The development of transition-metal-based antitumor drug candidates increases the metallopharmaceuticals study dramatically. Two trans-thiosemicarbazone-based, Schiff base palladium (Pd) (II) complexes, DMABTSPd (TSPd) and DMABPTSPd (PTSPd), were prepared and characterized as described in our previous study. Here, we investigated whether the two complexes have antitumor effect on human gastric adenocarcinoma cell lines, BGC-823 and SGC-7901, compared with normal human gastric mucosal epithelial cell line, Ges-1. The results show that the Pd complex with the bare amino group (DMABTSPd(TSPd)) can inhibit cell viabilities and induce apoptosis in human gastric carcinoma cells, rather than the Pd complex without the bare amino group (DMABPTSPd (PTSPd)). This occurs via a mitochondrial-related pathway by down-regulating the level of Bcl-2 expression and up-regulating the level of Bid expression. Meanwhile, DMABTSPd (TSPd) suppressed tumor growth via a mitochondrial-related pathway in a nude mouse tumor xenograft model derived from BGC-823 cells. These findings demonstrate that DMABTSPd (TSPd) is worthy of further structural optimization and representing a promising Pd complex for the development of a new antitumor therapeutic agent.

  8. Non-Typhoidal Salmonella Colonization in Chickens and Humans in the Mekong Delta of Vietnam.

    Science.gov (United States)

    Trung, N V; Carrique-Mas, J J; Nghia, N H; Tu, L T P; Mai, H H; Tuyen, H T; Campbell, J; Nhung, N T; Nhung, H N; Minh, P V; Chieu, T T B; Hieu, T Q; Mai, N T N; Baker, S; Wagenaar, J A; Hoa, N T; Schultsz, C

    2017-03-01

    Salmonellosis is a public health concern in both the developed and developing countries. Although the majority of human non-typhoidal Salmonella enterica (NTS) cases are the result of foodborne infections or person-to-person transmission, NTS infections may also be acquired by environmental and occupational exposure to animals. While a considerable number of studies have investigated the presence of NTS in farm animals and meat/carcasses, very few studies have investigated the risk of NTS colonization in humans as a result of direct animal exposure. We investigated asymptomatic NTS colonization in 204 backyard chicken farms, 204 farmers and 306 matched individuals not exposed to chicken farming, in southern Vietnam. Pooled chicken faeces, collected using boot or handheld swabs on backyard chicken farms, and rectal swabs from human participants were tested. NTS colonization prevalence was 45.6%, 4.4% and 2.6% for chicken farms, farmers and unexposed individuals, respectively. Our study observed a higher prevalence of NTS colonization among chicken farmers (4.4%) compared with age-, sex- and location- matched rural and urban individuals not exposed to chickens (2.9% and 2.0%). A total of 164 chicken NTS strains and 17 human NTS strains were isolated, and 28 serovars were identified. Salmonella Weltevreden was the predominant serovar in both chickens and humans. NTS isolates showed resistance (20-40%) against tetracycline, chloramphenicol, sulfamethoxazole-trimethoprim and ampicillin. Our study reflects the epidemiology of NTS colonization in chickens and humans in the Mekong delta of Vietnam and emphasizes the need of larger, preferably longitudinal studies to study the transmission dynamics of NTS between and within animal and human host populations. © 2016 The Authors. Zoonoses and Public Health Published by Blackwell Verlag GmbH.

  9. Pancreatic adenocarcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Schima, Wolfgang; Ba-Ssalamah, Ahmed; Koelblinger, Claus; Kulinna-Cosentini, Christiane [Medical University of Vienna, Department of Radiology, Vienna (Austria); Puespoek, Andreas [Medical University of Vienna, Department of Internal Medicine 4, Division of Gastroenterology and Hepatology, Vienna (Austria); Goetzinger, Peter [Medical University of Vienna, Austria, Department of Surgery, Vienna (Austria)

    2007-03-15

    Adenocarcinoma is the most common malignant pancreatic tumor, affecting the head of the pancreas in 60-70% of cases. By the time of diagnosis, at least 80% of tumors are unresectable. Helical computed tomography (CT) is very effective in detecting and staging adenocarcinoma, with a sensitivity of up to 90% for detection and an accuracy of 80-90% for staging, but it has limitations in detecting small cancers. Moreover, it is not very accurate for determining nonresectability because small liver metastases, peritoneal carcinomatosis, and subtle signs of vascular infiltration may be missed. Multidetector-row CT (MDCT) has brought substantial improvements with its inherent ability to visualize vascular involvement in three dimensions. MDCT has been found to be at least equivalent to contrast-enhanced magnetic resonance imaging (MRI) for detecting adenocarcinoma. MRI can be used as a problem-solving tool in equivocal CT: MRI may help rule out pitfalls, such as inflammatory pseudotumor, focal lipomatosis, abscess, or cystic tumors. Mangafodipir-enhanced MRI reveals a very high tumor-pancreas contrast, which helps in diagnosing small cancers. Endosonography is, if available, also a very accurate tool for detecting small cancers, with a sensitivity of up to 98%. It is the technique of choice for image-guided biopsy if a histologic diagnosis is required for further therapy. (orig.)

  10. [Cytotoxic effect in human colon of enterohemorrhagic Escherichia coli isolated from calves with bloody diarrhea].

    Science.gov (United States)

    Pistone Creydt, V; Venzano, A; Vilte, D A; Mercado, E C; Ibarra, C

    2005-01-01

    Shiga toxin-producing E. coli (STEC) is one of the most important emergent pathogen in foods, being its main reservoir bovine cattle. STEC can cause diarrhea, hemorrhagic colitis and hemolytic-uremic syndrome. The present work have studied the cytotoxic action in human colon of cultures of two STEC strains isolated from faeces of calves with bloody diarrhea. Colonic mucosa was mounted as a diaphragm in a Ussing chamber and incubated with the cultures of pathogenic strains. Net water flow (Jw) decreased and the short-circuit current (Isc) increased significantly (p < 0.01) compared to negative control. Tissues showed an erosion of the mucose, epithelial exfoliation, and presence of pseudo-membranes in the lumen. Mild circulatory lesions were observed in the lamina propia. A moderate neutrophils infiltration was observed in the lumen and into the epithelial cells. Colonic crypts were not disrupted. Both experimental strains caused a similar lesion on colon tissues. This is the first study that shows that cultures of STEC strains isolated from bovine cattle produce cytotoxic effects in vitro in human colon.

  11. Colonization with the enteric protozoa Blastocystis is associated with increased diversity of human gut bacterial microbiota.

    Science.gov (United States)

    Audebert, Christophe; Even, Gaël; Cian, Amandine; Loywick, Alexandre; Merlin, Sophie; Viscogliosi, Eric; Chabé, Magali

    2016-05-05

    Alterations in the composition of commensal bacterial populations, a phenomenon known as dysbiosis, are linked to multiple gastrointestinal disorders, such as inflammatory bowel disease and irritable bowel syndrome, or to infections by diverse enteric pathogens. Blastocystis is one of the most common single-celled eukaryotes detected in human faecal samples. However, the clinical significance of this widespread colonization remains unclear, and its pathogenic potential is controversial. To address the issue of Blastocystis pathogenicity, we investigated the impact of colonization by this protist on the composition of the human gut microbiota. For that purpose, we conducted a cross-sectional study including 48 Blastocystis-colonized patients and 48 Blastocystis-free subjects and performed an Ion Torrent 16S rDNA gene sequencing to decipher the Blastocystis-associated gut microbiota. Here, we report a higher bacterial diversity in faecal microbiota of Blastocystis colonized patients, a higher abundance of Clostridia as well as a lower abundance of Enterobacteriaceae. Our results contribute to suggesting that Blastocystis colonization is usually associated with a healthy gut microbiota, rather than with gut dysbiosis generally observed in metabolic or infectious inflammatory diseases of the lower gastrointestinal tract.

  12. Colonization with the enteric protozoa Blastocystis is associated with increased diversity of human gut bacterial microbiota

    Science.gov (United States)

    Audebert, Christophe; Even, Gaël; Cian, Amandine; Safadi, Dima El; Certad, Gabriela; Delhaes, Laurence; Pereira, Bruno; Nourrisson, Céline; Poirier, Philippe; Wawrzyniak, Ivan; Delbac, Frédéric; Morelle, Christelle; Bastien, Patrick; Lachaud, Laurence; Bellanger, Anne-Pauline; Botterel, Françoise; Candolfi, Ermanno; Desoubeaux, Guillaume; Morio, Florent; Pomares, Christelle; Rabodonirina, Meja; Loywick, Alexandre; Merlin, Sophie; Viscogliosi, Eric; Chabé, Magali

    2016-01-01

    Alterations in the composition of commensal bacterial populations, a phenomenon known as dysbiosis, are linked to multiple gastrointestinal disorders, such as inflammatory bowel disease and irritable bowel syndrome, or to infections by diverse enteric pathogens. Blastocystis is one of the most common single-celled eukaryotes detected in human faecal samples. However, the clinical significance of this widespread colonization remains unclear, and its pathogenic potential is controversial. To address the issue of Blastocystis pathogenicity, we investigated the impact of colonization by this protist on the composition of the human gut microbiota. For that purpose, we conducted a cross-sectional study including 48 Blastocystis-colonized patients and 48 Blastocystis-free subjects and performed an Ion Torrent 16S rDNA gene sequencing to decipher the Blastocystis-associated gut microbiota. Here, we report a higher bacterial diversity in faecal microbiota of Blastocystis colonized patients, a higher abundance of Clostridia as well as a lower abundance of Enterobacteriaceae. Our results contribute to suggesting that Blastocystis colonization is usually associated with a healthy gut microbiota, rather than with gut dysbiosis generally observed in metabolic or infectious inflammatory diseases of the lower gastrointestinal tract. PMID:27147260

  13. NMR metabolomics of human lung tumours reveals distinct metabolic signatures for adenocarcinoma and squamous cell carcinoma.

    Science.gov (United States)

    Rocha, Cláudia M; Barros, António S; Goodfellow, Brian J; Carreira, Isabel M; Gomes, Ana; Sousa, Vitor; Bernardo, João; Carvalho, Lina; Gil, Ana M; Duarte, Iola F

    2015-01-01

    Lung tumour subtyping, particularly the distinction between adenocarcinoma (AdC) and squamous cell carcinoma (SqCC), is a critical diagnostic requirement. In this work, the metabolic signatures of lung carcinomas were investigated through (1)H NMR metabolomics, with a view to provide additional criteria for improved diagnosis and treatment planning. High Resolution Magic Angle Spinning Nuclear Magnetic Resonance (NMR) spectroscopy was used to analyse matched tumour and adjacent control tissues from 56 patients undergoing surgical excision of primary lung carcinomas. Multivariate modeling allowed tumour and control tissues to be discriminated with high accuracy (97% classification rate), mainly due to significant differences in the levels of 13 metabolites. Notably, the magnitude of those differences were clearly distinct for AdC and SqCC: major alterations in AdC were related to phospholipid metabolism (increased phosphocholine, glycerophosphocholine and phosphoethanolamine, together with decreased acetate) and protein catabolism (increased peptide moieties), whereas SqCC had stronger glycolytic and glutaminolytic profiles (negatively correlated variations in glucose and lactate and positively correlated increases in glutamate and alanine). Other tumour metabolic features were increased creatine, glutathione, taurine and uridine nucleotides, the first two being especially prominent in SqCC and the latter in AdC. Furthermore, multivariate analysis of AdC and SqCC profiles allowed their discrimination with a 94% classification rate, thus showing great potential for aiding lung tumours subtyping. Overall, this study has provided new, clear evidence of distinct metabolic signatures for lung AdC and SqCC, which can potentially impact on diagnosis and provide important leads for future research on novel therapeutic targets or imaging tracers. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  14. Decorin in Human Colon Cancer: Localization In Vivo and Effect on Cancer Cell Behavior In Vitro.

    Science.gov (United States)

    Nyman, Marie C; Sainio, Annele O; Pennanen, Mirka M; Lund, Riikka J; Vuorikoski, Sanna; Sundström, Jari T T; Järveläinen, Hannu T

    2015-09-01

    Decorin is generally recognized as a tumor suppressing molecule. Nevertheless, although decorin has been shown to be differentially expressed in malignant tissues, it has often remained unclear whether, in addition to non-malignant stromal cells, cancer cells also express it. Here, we first used two publicly available databases to analyze the current information about decorin expression and immunoreactivity in normal and malignant human colorectal tissue samples. The analyses demonstrated that decorin expression and immunoreactivity may vary in cancer cells of human colorectal tissues. Therefore, we next examined decorin expression in normal, premalignant and malignant human colorectal tissues in more detail using both in situ hybridization and immunohistochemistry for decorin. Our results invariably demonstrate that malignant cells within human colorectal cancer tissues are devoid of both decorin mRNA and immunoreactivity. Identical results were obtained for cells of neuroendocrine tumors of human colon. Using RT-qPCR, we showed that human colon cancer cell lines are also decorin negative, in accordance with the above in vivo results. Finally, we demonstrate that decorin transduction of human colon cancer cell lines causes a significant reduction in their colony forming capability. Thus, strategies to develop decorin-based adjuvant therapies for human colorectal malignancies are highly rational. © The Author(s) 2015.

  15. Tumor-specific expression of anti-mdr1 ribozyme selectively restores chemosensitivity in multidrug-resistant colon-adenocarcinoma cells.

    Science.gov (United States)

    Gao, Z; Gao, Z; Fields, J Z; Boman, B M

    1999-07-30

    P-glycoprotein (Pgp)-conferred multidrug resistance (MDR) is expressed in cancer and in normal colon tissues and has important physiological functions. In order to selectively reverse MDR in malignant tissue without disrupting the function of normal colonocytes, a retroviral vector (pCEAMR) containing anti-mdr1 ribozyme coupled to the carcino-embryonic-antigen (CEA) promoter was constructed and introduced into resistant colon-cancer cells (SW1116R) that produce CEA and into control resistant cells (HeLaK) that do not produce CEA. Anti-mdr1 ribozyme was expressed in SW1116R cells but not in HeLaK cells. Subsequently, the expression of mdr1 mRNA and Pgp decreased significantly in the transfected SW1116R cells, and was even lower than in parent non-resistant SW1116 cells. The functional ability of Pgp to facilitate rhodamine 123 (Rh123) efflux showed that the transfected SW1116R cells with low Pgp expression retained Rh123, whereas non-transfected SW1116R cells with high Pgp expression released the dye quickly. There was no difference in mdr1 mRNA or in Pgp between non-transfected and transfected HeLaK cells. Drug resistance to doxorubicin (DOX) decreased 93.1% in the transfected SW1116R cells, while no change in drug resistance occurred in the infected HeLaK cells. DOX could clearly inhibit the growth of transfected SW1116R tumors but had no effect on untransfected and on transfected HeLaK cells in vivo. These results indicate that our anti-mdr1 ribozyme is expressed only in CEA-producing colon-cancer cells and reverses their drug resistance selectively.

  16. Separation of water-soluble metabolites of benzo[a]pyrene formed by cultured human colon

    DEFF Research Database (Denmark)

    1979-01-01

    A method has been developed to separate conjugated metabolites of benzo[a]pyrene into three major fractions: sulfate esters, glucuronides and glutathione conjugates. In cultured human colon, formation of sulfate esters and glutathione conjugates is the major conjugation pathway, while formation o...

  17. Genetics of the pig tapeworm in Madagascar reveal a history of human dispersal and colonization

    Science.gov (United States)

    An intricate history of human dispersal and geographic colonization has strongly affected the distribution of obligate parasites circulating among people. Among these parasites, the pig tapeworm Taenia solium occurs throughout the world as the causative agent of cysticercosis, one of the most serio...

  18. Interstitial cells of Cajal in human colon and in Hirschsprung's disease

    DEFF Research Database (Denmark)

    Vanderwinden, J M; Rumessen, J J; Liu, H

    1996-01-01

    Subpopulations of interstitial cells of Cajal are regarded as the source of spontaneous slow waves of the gut musculature (pacemaker cells). Their ontogeny remains unclear, but a role of the tyrosine kinase receptor c-kit in their development has recently been recognized. This study examined the ...... the interstitial cells in the human colon and in Hirschsprung's disease (aganglionosis)....

  19. Emission spectral analysis of caspase-3 activation during artesunate (ART)-induced apoptosis of human lung adenocarcinoma cell

    Science.gov (United States)

    Pan, Wen-liang; Chen, Tong-sheng; Qu, Junle

    2009-02-01

    Artesunate (ART), a semi-synthetic derivative of the sesquiterpene artemisinin extracted from the Chinese herb Artemisia annua, exerts a broad spectrum of clinical activity against human cancers. Artemisinin-derivative combination chemotherapy is recommended by WHO since it acts rapidly and is well tolerated and particularly effective. In present investigation, we used CKK-8 assay to assess the inhibitory effects of ART on human lung adenocarcinoma (ASTC-a-1) cells. Apoptotic activity of ART in ASTC-a-1 cells was detected by means of nuclear staining with Hoechst33258. In order to monitor the activity of caspase-3 during ART-induced ASTC-a-1 cells apoptosis, the dynamical emission spectra of SCAT3, a FRET plasmid based on GFPs, were performed inside living cell expressed stably with SCAT3 after ART treatment. The results showed that (1) ART could inhibit ASTC-a-1 cells proliferation in a dose-dependent manner; (2) chromatin condensation was observed after ART treatment for 48 h; (3) the SCAT3 inside living cells were cleaved after ART treatment for 48 h, implying that caspase-3 was involved in the ART-induced apoptosis.

  20. Trolox induces inhibition of cell proliferation and apoptosis in human colon cancer cells

    OpenAIRE

    Li-Guang Yang; Xiang-An Tian; Xiao-Yan Li; Jian-Guo Huang; Nai-Qing Liu; Qin-Li Sun

    2015-01-01

    In the present study, the effect of trolox on human colon cancer cell lines was investigated. The results revealed that trolox treatment caused inhibition of cell growth in T84 and HCT-15 colon cancer cell lines in a dose-dependent manner. The inhibition was significant at 50 µM of trolox after 48 hours in both cell lines. Trolox treatment promoted expression of p38 and inhibited expression of survivin and Akt. It also induced cleavage of PARP and caspase-3 and ultimately induced apoptosis in...

  1. Resveratrol Treatment Inhibits Proliferation of and Induces Apoptosis in Human Colon Cancer Cells.

    Science.gov (United States)

    Feng, Miao; Zhong, Lu-Xing; Zhan, Zheng-Yu; Huang, Zhi-Hao; Xiong, Jian-Ping

    2016-04-04

    Resveratrol, a natural isolate from plant sources, has a long and important history in traditional Chinese medicine. In the present study we investigated the effect of resveratrol on human colon cancer cell lines. We used the Cell Counting kit-8 (CCK-8) for determination of colon cancer cell viability. Apoptosis induction was analyzed using the DeadEnd™ Colorimetric TUNEL System (Promega, Madison, WI, USA). The siRNA Transfection Reagent kit (Santa Cruz Biotechnology, Inc.) was used for the administration of COX-2 silencer RNA (siRNA) into the colon cancer cells. Primer Express® software for Real-Time PCR ver. 3.0 (Applied Biosystems, Foster City, CA, USA) was used to prepare the primers for RT-PCR. The results revealed that exposure of colon cancer cells to resveratrol inhibited cell viability. Resveratrol exhibited a significant inhibitory effect on cell viability at 30 μM concentration after 48 h of exposure. We observed that 30-μM doses of resveratrol for 72 h led to 18, 29, and 34% reduction in the viability of HCA-17, SW480, and HT29 cells, respectively. It also significantly induced apoptosis in both of the tested carcinoma cell lines. The population of apoptotic cells in HCA-17 and SW480 cell lines after 48 h of resveratrol treatment was 59.8±4 and 67.2±4%, respectively, compared to 2.3±1% in the control cells. The colon cancer cells exposed to resveratrol showed significantly lower cyclooxygenase-2 and prostaglandin receptor expression. Treatment of colon cancer cells with the inhibitor of cyclooxygenase-2, indomethacin, and administration of silencer RNA for cyclooxygenase-2 also produced similar results. These findings suggest that resveratrol treatment can be a promising strategy for the treatment of colon cancer.

  2. Antimicrobial Use, Human Gut Microbiota and Clostridium difficile Colonization and Infection

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    Caroline Vincent

    2015-07-01

    Full Text Available Clostridium difficile infection (CDI is the most important cause of nosocomial diarrhea. Broad-spectrum antimicrobials have profound detrimental effects on the structure and diversity of the indigenous intestinal microbiota. These alterations often impair colonization resistance, allowing the establishment and proliferation of C. difficile in the gut. Studies involving animal models have begun to decipher the precise mechanisms by which the intestinal microbiota mediates colonization resistance against C. difficile and numerous investigations have described gut microbiota alterations associated with C. difficile colonization or infection in human subjects. Fecal microbiota transplantation (FMT is a highly effective approach for the treatment of recurrent CDI that allows the restoration of a healthy intestinal ecosystem via infusion of fecal material from a healthy donor. The recovery of the intestinal microbiota after FMT has been examined in a few reports and work is being done to develop custom bacterial community preparations that could be used as a replacement for fecal material.

  3. A novel histone deacetylase inhibitor Chidamide induces apoptosis of human colon cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Lin [Department of Oncology, Zhong-Da Hospital of Southeast University, Nanjing 210009, Jiangsu (China); Chen, Baoan, E-mail: wenyu811@126.com [Department of Oncology, Zhong-Da Hospital of Southeast University, Nanjing 210009, Jiangsu (China); Qin, Shukui [Chinese PLA Cancer Center, The 81st PLA Hospital, Nanjing 210002, Jiangsu (China); Li, Suyi; He, Xiangming [Department of Oncology, Zhong-Da Hospital of Southeast University, Nanjing 210009, Jiangsu (China); Qiu, Shaomin; Zhao, Wei; Zhao, Hong [Department of Internal Medicine, Nanjing Municipal Cancer Hospital, Nanjing 210003, Jiangsu (China)

    2010-02-05

    Many studies have demonstrated that histone deacetylase (HDAC) inhibitors induce various tumor cells to undergo apoptosis, and such inhibitors have been used in different clinical trials against different human cancers. In this study, we designed and synthesized a novel HDAC inhibitor, Chidamide. We showed that Chidamide was able to increase the acetylation levels of histone H3 and to inhibit the PI3K/Akt and MAPK/Ras signaling pathways, which resulted in arresting colon cancer cells at the G1 phase of the cell cycle and promoting apoptosis. As a result, the proliferation of colon cancer cells was suppressed in vitro. Our data support the potential application of Chidamide as an anticancer agent in treating colon cancer. Future studies are needed to demonstrate its in vivo efficacy.

  4. Plaque assay for human coronavirus NL63 using human colon carcinoma cells

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    Drosten Christian

    2008-11-01

    Full Text Available Abstract Background Coronaviruses cause a broad range of diseases in animals and humans. Human coronavirus (hCoV NL63 is associated with up to 10% of common colds. Viral plaque assays enable the characterization of virus infectivity and allow for purifying virus stock solutions. They are essential for drug screening. Hitherto used cell cultures for hCoV-NL63 show low levels of virus replication and weak and diffuse cytopathogenic effects. It has not yet been possible to establish practicable plaque assays for this important human pathogen. Results 12 different cell cultures were tested for susceptibility to hCoV-NL63 infection. Human colon carcinoma cells (CaCo-2 replicated virus more than 100 fold more efficiently than commonly used African green monkey kidney cells (LLC-MK2. CaCo-2 cells showed cytopathogenic effects 4 days post infection. Avicel, agarose and carboxymethyl-cellulose overlays proved suitable for plaque assays. Best results were achieved with Avicel, which produced large and clear plaques from the 4th day of infection. The utility of plaque assays with agrose overlay was demonstrated for purifying virus, thereby increasing viral infectivity by 1 log 10 PFU/mL. Conclusion CaCo-2 cells support hCoV-NL63 better than LLC-MK2 cells and enable cytopathogenic plaque assays. Avicel overlay is favourable for plaque quantification, and agarose overlay is preferred for plaque purification. HCoV-NL63 virus stock of increased infectivity will be beneficial in antiviral screening, animal modelling of disease, and other experimental tasks.

  5. CNTN-1 Enhances Chemoresistance in Human Lung Adenocarcinoma Through Induction of Epithelial-Mesenchymal Transition by Targeting the PI3K/Akt Pathway

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    Ruijie Zhang

    2017-09-01

    Full Text Available Background/Aims: Chemoresistance has been a major obstacle to the effective treatment of lung cancer. Previously, we found that contactin-1 (CNTN-1 is related to cisplatin resistance in lung adenocarcinoma. Here, we aimed to investigate the underlying mechanism behind the role of CNTN-1 in cisplatin resistance in lung adenocarcinoma. Methods: EMT-associated phenotypes, including alterations in cellular morphology and marker (E-cadherin, N-cadherin and Vimentin expression, were compared between A549 cells and A549/DDP cells (a cisplatin-resistant cell line of lung adenocarcinoma with abnormal CNTN-1 expression by using real-time time PCR and Western blotting. Other methods, including CNTN-1 overexpression in A549 cells and CNTN-1 knockdown in A549/DDP cells, were also used to investigate the role of CNTN-1 in mediating the EMT phenotype and thr resulting cisplatin resistance and malignant progression of cancer cells in vitro and in vivo. Results: A549/DDP cells exhibited an EMT phenotype and aggravated malignant behaviors. CNTN-1 knockdown in A549/DDP cells partly reversed the EMT phenotype, increased drug sensitivity, and attenuated the malignant progression whereas CNTN-1 overexpression in A549 cells resulted in the opposite trend. Furthermore, the PI3K/Akt pathway was involved in the effects of CNTN-1 on EMT progression in A549/DDP cells, verified by the xenograft mouse model. Conclusion: CNTN-1 promotes cisplatin resistance in human cisplatin-resistant lung adenocarcinoma through inducing the EMT process by activating the PI3K/Akt signaling pathway. CNTN-1 may be a potential therapeutic target to reverse chemoresistance in cisplatin-resistant lung adenocarcinoma.

  6. CNTN-1 Enhances Chemoresistance in Human Lung Adenocarcinoma Through Induction of Epithelial-Mesenchymal Transition by Targeting the PI3K/Akt Pathway.

    Science.gov (United States)

    Zhang, Ruijie; Sun, Shenghua; Ji, Fuyun; Liu, Chun; Lin, Hua; Xie, Lihua; Yang, Honghui; Tang, Wenxiang; Zhou, Yan; Xu, Jianping; Li, Pei

    2017-01-01

    Chemoresistance has been a major obstacle to the effective treatment of lung cancer. Previously, we found that contactin-1 (CNTN-1) is related to cisplatin resistance in lung adenocarcinoma. Here, we aimed to investigate the underlying mechanism behind the role of CNTN-1 in cisplatin resistance in lung adenocarcinoma. EMT-associated phenotypes, including alterations in cellular morphology and marker (E-cadherin, N-cadherin and Vimentin) expression, were compared between A549 cells and A549/DDP cells (a cisplatin-resistant cell line of lung adenocarcinoma with abnormal CNTN-1 expression) by using real-time time PCR and Western blotting. Other methods, including CNTN-1 overexpression in A549 cells and CNTN-1 knockdown in A549/DDP cells, were also used to investigate the role of CNTN-1 in mediating the EMT phenotype and thr resulting cisplatin resistance and malignant progression of cancer cells in vitro and in vivo. A549/DDP cells exhibited an EMT phenotype and aggravated malignant behaviors. CNTN-1 knockdown in A549/DDP cells partly reversed the EMT phenotype, increased drug sensitivity, and attenuated the malignant progression whereas CNTN-1 overexpression in A549 cells resulted in the opposite trend. Furthermore, the PI3K/Akt pathway was involved in the effects of CNTN-1 on EMT progression in A549/DDP cells, verified by the xenograft mouse model. CNTN-1 promotes cisplatin resistance in human cisplatin-resistant lung adenocarcinoma through inducing the EMT process by activating the PI3K/Akt signaling pathway. CNTN-1 may be a potential therapeutic target to reverse chemoresistance in cisplatin-resistant lung adenocarcinoma. © 2017 The Author(s). Published by S. Karger AG, Basel.

  7. Mucinous adenocarcinoma of the appendix: A case report and ...

    African Journals Online (AJOL)

    Primary adenocarcinoma of the appendix is a rare disease as compared with cancer of the colon. It is common in patients in the middle age. Mucinous adenocarcinoma is one of the histological types seen. The usual presentation of patients is acute appendicitis or peri –appendicular abscess. Diagnosis is often made after ...

  8. The effects of arsenic trioxide on DNA synthesis and genotoxicity in human colon cancer cells.

    Science.gov (United States)

    Stevens, Jacqueline J; Graham, Barbara; Walker, Alice M; Tchounwou, Paul B; Rogers, Christian

    2010-05-01

    Colon cancer is the third leading cause of cancer-related deaths worldwide. Recent studies in our laboratory have demonstrated that arsenic trioxide is cytotoxic in human colon cancer (HT-29), lung (A549) and breast (MCF-7) carcinoma cells. The purpose of the present study is to investigate the effects of arsenic trioxide on DNA synthesis and the possible genotoxic effects on human colon cancer cells. HT-29 cells were cultured according to standard protocol, followed by exposure to various doses (0, 2, 4, 6, 8, 10, and 12 microg/mL) of arsenic trioxide for 24 h. The proliferative response (DNA synthesis) to arsenic trioxide was assessed by [(3)H]thymidine incorporation. The genotoxic effects of arsenic-induced DNA damage in a human colon cancer cell line was evaluated by the alkaline single cell gel electrophoresis. Results indicated that arsenic trioxide affected DNA synthesis in HT-29 cells in a biphasic manner; showing a slight but not significant increase in cell proliferation at lower levels of exposure (2, 4 and 6 microg/mL) followed by a significant inhibition of cell proliferation at higher doses (i.e., 8 and 10 microg/mL). The study also confirmed that arsenic trioxide exposure caused genotoxicity as revealed by the significant increase in DNA damage, comet tail-lengths, and tail moment when compared to non-exposed cells. Results of the [(3)H]thymidine incorporation assay and comet assay revealed that exposure to arsenic trioxide affected DNA synthesis and exhibited genotoxic effects in human colon cancer cells.

  9. The Effects of Arsenic Trioxide on DNA Synthesis and Genotoxicity in Human Colon Cancer Cells

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    Christian Rogers

    2010-04-01

    Full Text Available Colon cancer is the third leading cause of cancer-related deaths worldwide. Recent studies in our laboratory have demonstrated that arsenic trioxide is cytotoxic in human colon cancer (HT-29, lung (A549 and breast (MCF-7 carcinoma cells. The purpose of the present study is to investigate the effects of arsenic trioxide on DNA synthesis and the possible genotoxic effects on human colon cancer cells. HT-29 cells were cultured according to standard protocol, followed by exposure to various doses (0, 2, 4, 6, 8, 10, and 12 μg/mL of arsenic trioxide for 24 h. The proliferative response (DNA synthesis to arsenic trioxide was assessed by [3H]thymidine incorporation. The genotoxic effects of arsenic-induced DNA damage in a human colon cancer cell line was evaluated by the alkaline single cell gel electrophoresis. Results indicated that arsenic trioxide affected DNA synthesis in HT-29 cells in a biphasic manner; showing a slight but not significant increase in cell proliferation at lower levels of exposure (2, 4 and 6 µg/mL followed by a significant inhibition of cell proliferation at higher doses (i.e., 8 and 10 µg/mL. The study also confirmed that arsenic trioxide exposure caused genotoxicity as revealed by the significant increase in DNA damage, comet tail-lengths, and tail moment when compared to non-exposed cells. Results of the [3H]thymidine incorporation assay and comet assay revealed that exposure to arsenic trioxide affected DNA synthesis and exhibited genotoxic effects in human colon cancer cells.

  10. Establishment and Characterization of a Novel Chinese Human Lung Adenocarcinoma Cell Line CPA-Yang2 in Immunodeficient Mice

    OpenAIRE

    Shunfang YANG; Su, Jianzhong; Meiping SHI; Lanxiang ZHAO; Zhang, Peiling; Cao, Jie; Lu, Jianying; Xie, Wenhui

    2009-01-01

    Background and objective The recurrence, metastasis and multidrug resistance (MDR) in lung cancer are the tough problems worldwide. This study was to establish a novel chinese lung adenocarcinoma cell line with high metastasis potential for exploring the mechanism of reccurrence, development and MDR in lung cancer. Methods The cell came from the abdominal dropsy of a fifty-six years old female patient with lung adenocarcinoma and the tumor markers CA125, CYFRA21-1, CEA, NSE were detected to b...

  11. Colon Cancer Metastatic to the Biliary Tree

    OpenAIRE

    Strauss, Alexandra T.; Clayton, Steven B.; Markow, Michael; Mamel, Jay

    2016-01-01

    Metastasis of colon adenocarcinoma is commonly found in the lung, liver, or peritoneum. Common bile duct (CBD) tumors related to adenomas from familial adenomatous polyposis metastasizing from outside of the gastrointestinal tract have been reported. We report a case of biliary colic due to metastatic colon adenocarcinoma to the CBD. Obstructive jaundice with signs of acalculous cholecystitis on imaging in a patient with a history of colon cancer should raise suspicion for metastasis to CBD.

  12. Bad is not involved in DHA-induced apoptosis in human lung adenocarcinoma ASTC-a-1 cells

    Science.gov (United States)

    Yu, Huai-na; Lu, Ying-ying; Chen, Tong-sheng

    2011-03-01

    Dihydroartemisinin (DHA), a first-line anti-malarial drug with low toxicity, has been shown to possess promising anticancer activities and induce cancer cell death through apoptotic pathway, but the molecular mechanisms are not well understood. In this paper, we focus on whether Bad, a BH3-only pro-apoptotic protein, is involved in apoptotic cell death in DHA-treated human lung adenocarcinoma (ASTC-a-1) cells. Confocal fluorescence microscope imaging was used to monitor the temporal and spatial distribution of Bad in single living cells. Our results indicate that Bad is still located in cytoplasm and does not translocate to mitochondria after treatment with DHA for 24 h, while only a small proportion of Bad located in cytoplasm in the STS-treated cells for 6 h. These results show for the first time that Bad is not involved in DHA-induced apoptosis in ASTC-a-1 cells, which could give more evidence for the molecular mechanisms of apoptosis induced by DHA.

  13. Cuminaldehyde from Cinnamomum verum Induces Cell Death through Targeting Topoisomerase 1 and 2 in Human Colorectal Adenocarcinoma COLO 205 Cells

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    Kuen-daw Tsai

    2016-05-01

    Full Text Available Cinnamomum verum, also called true cinnamon tree, is employed to make the seasoning cinnamon. Furthermore, the plant has been used as a traditional Chinese herbal medication. We explored the anticancer effect of cuminaldehyde, an ingredient of the cortex of the plant, as well as the molecular biomarkers associated with carcinogenesis in human colorectal adenocarcinoma COLO 205 cells. The results show that cuminaldehyde suppressed growth and induced apoptosis, as proved by depletion of the mitochondrial membrane potential, activation of both caspase-3 and -9, and morphological features of apoptosis. Moreover, cuminaldehyde also led to lysosomal vacuolation with an upregulated volume of acidic compartment and cytotoxicity, together with inhibitions of both topoisomerase I and II activities. Additional study shows that the anticancer activity of cuminaldehyde was observed in the model of nude mice. Our results suggest that the anticancer activity of cuminaldehyde in vitro involved the suppression of cell proliferative markers, topoisomerase I as well as II, together with increase of pro-apoptotic molecules, associated with upregulated lysosomal vacuolation. On the other hand, in vivo, cuminaldehyde diminished the tumor burden that would have a significant clinical impact. Furthermore, similar effects were observed in other tested cell lines. In short, our data suggest that cuminaldehyde could be a drug for chemopreventive or anticancer therapy.

  14. Methanolic Extracts from Brown Seaweeds Dictyota cilliolata and Dictyota menstrualis Induce Apoptosis in Human Cervical Adenocarcinoma HeLa Cells

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    Dayanne Lopes Gomes

    2015-04-01

    Full Text Available Carcinoma of the uterine cervix is the second most common female tumor worldwide, surpassed only by breast cancer. Natural products from seaweeds evidencing apoptotic activity have attracted a great deal of attention as new leads for alternative and complementary preventive or therapeutic anticancer agents. Here, methanol extracts from 13 species of tropical seaweeds (Rhodophytas, Phaeophyta and Chlorophyta collected from the Northeast of Brazil were assessed as apoptosis-inducing agents on human cervical adenocarcinoma (HeLa. All extracts showed different levels of cytotoxicity against HeLa cells; the most potent were obtained from the brown alga Dictyota cilliolata (MEDC and Dictyota menstrualis (MEDM. In addition, MEDC and MEDM also inhibits SiHa (cervix carcinoma cell proliferation. Studies with these two extracts using flow cytometry and fluorescence microscopy showed that HeLa cells exposed to MEDM and MEDC exhibit morphological and biochemical changes that characterize apoptosis as shown by loss of cell viability, chromatin condensation, phosphatidylserine externalization, and sub-G1 cell cycle phase accumulation, also MEDC induces cell cycle arrest in cell cycle phase S. Moreover, the activation of caspases 3 and 9 by these extracts suggests a mitochondria-dependent apoptosis route. However, other routes cannot be ruled out. Together, these results point out the methanol extracts of the brown algae D. mentrualis and D. cilliolata as potential sources of molecules with antitumor activity.

  15. Melatonin inhibits the migration of human lung adenocarcinoma A549 cell lines involving JNK/MAPK pathway.

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    Qiaoyun Zhou

    Full Text Available OBJECTIVE: Melatonin, an indolamine produced and secreted predominately by the pineal gland, exhibits a variety of physiological functions, possesses antioxidant and antitumor properties. But, the mechanisms for the anti-cancer effects are unknown. The present study explored the effects of melatonin on the migration of human lung adenocarcinoma A549 cells and its mechanism. METHODS: MTT assay was employed to measure the viability of A549 cells treated with different concentrations of melatonin. The effect of melatonin on the migration of A549 cells was analyzed by wound healing assay. Occludin location was observed by immunofluorescence. The expression of occludin, osteopontin (OPN, myosin light chain kinase (MLCK and phosphorylation of myosin light chain (MLC, JNK were detected by western blots. RESULTS: After A549 cells were treated with melatonin, the viability and migration of the cells were inhibited significantly. The relative migration rate of A549 cells treated with melatonin was only about 20% at 24 h. The expression level of OPN, MLCK and phosphorylation of MLC of A549 cells were reduced, while the expression of occludin was conversely elevated, and occludin located on the cell surface was obviously increased. The phosphorylation status of JNK in A549 cells was also reduced when cells were treated by melatonin. CONCLUSIONS: Melatonin significantly inhibits the migration of A549 cells, and this may be associated with the down-regulation of the expression of OPN, MLCK, phosphorylation of MLC, and up-regulation of the expression of occludin involving JNK/MAPK pathway.

  16. Dual prognostic significance of tumour-associated macrophages in human pancreatic adenocarcinoma treated or untreated with chemotherapy.

    Science.gov (United States)

    Di Caro, Giuseppe; Cortese, Nina; Castino, Giovanni Francesco; Grizzi, Fabio; Gavazzi, Francesca; Ridolfi, Cristina; Capretti, Giovanni; Mineri, Rossana; Todoric, Jelena; Zerbi, Alessandro; Allavena, Paola; Mantovani, Alberto; Marchesi, Federica

    2016-10-01

    Tumour-associated macrophages (TAMs) play key roles in tumour progression. Recent evidence suggests that TAMs critically modulate the efficacy of anticancer therapies, raising the prospect of their targeting in human cancer. In a large retrospective cohort study involving 110 patients with pancreatic ductal adenocarcinoma (PDAC), we assessed the density of CD68-TAM immune reactive area (%IRA) at the tumour-stroma interface and addressed their prognostic relevance in relation to postsurgical adjuvant chemotherapy (CTX). In vitro, we dissected the synergism of CTX and TAMs. In human PDAC, TAMs predominantly exhibited an immunoregulatory profile, characterised by expression of scavenger receptors (CD206, CD163) and production of interleukin 10 (IL-10). Surprisingly, while the density of TAMs associated to worse prognosis and distant metastasis, CTX restrained their protumour prognostic significance. High density of TAMs at the tumour-stroma interface positively dictated prognostic responsiveness to CTX independently of T-cell density. Accordingly, in vitro, gemcitabine-treated macrophages became tumoricidal, activating a cytotoxic gene expression programme, inhibiting their protumoural effect and switching to an antitumour phenotype. In patients with human PDAC, neoadjuvant CTX was associated to a decreased density of CD206(+) and IL-10(+) TAMs at the tumour-stroma interface. Overall, our data highlight TAMs as critical determinants of prognostic responsiveness to CTX and provide clinical and in vitro evidence that CTX overall directly re-educates TAMs to restrain tumour progression. These results suggest that the quantification of TAMs could be exploited to select patients more likely to respond to CTX and provide the basis for novel strategies aimed at re-educating macrophages in the context of CTX. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  17. 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.

  18. Flux analysis of the human proximal colon using anaerobic digestion model 1.

    Science.gov (United States)

    Motelica-Wagenaar, Anne Marieke; Nauta, Arjen; van den Heuvel, Ellen G H M; Kleerebezem, Robbert

    2014-08-01

    The colon can be regarded as an anaerobic digestive compartment within the gastro intestinal tract (GIT). An in silico model simulating the fluxes in the human proximal colon was developed on basis of the anaerobic digestion model 1 (ADM1), which is traditionally used to model waste conversion to biogas. Model calibration was conducted using data from in vitro fermentation of the proximal colon (TIM-2), and, amongst others, supplemented with the bio kinetics of prebiotic galactooligosaccharides (GOS) fermentation. The impact of water and solutes absorption by the host was also included. Hydrolysis constants of carbohydrates and proteins were estimated based on total short chain fatty acids (SCFA) and ammonia production in vitro. Model validation was established using an independent dataset of a different in vitro model: an in vitro three-stage continuous culture system. The in silico model was shown to provide quantitative insight in the microbial community structure in terms of functional groups, and the substrate and product fluxes between these groups as well as the host, as a function of the substrate composition, pH and the solids residence time (SRT). The model confirms the experimental observation that methanogens are washed out at low pH or low SRT-values. The in silico model is proposed as useful tool in the design of experimental setups for in vitro experiments by giving insight in fermentation processes in the proximal human colon. Copyright © 2014. Published by Elsevier Ltd.

  19. Secretory leukocyte protease inhibitor in punch biopsies from human colonic mucosa

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    Max Nyström

    2001-01-01

    Full Text Available Secretory leukocyte protease inhibitor (SLPI is a wellknown protease inhibitor. Its function is thought to be protease/protease-inhibitor balance. Free proteolytic activity, mainly pancreatic elastase, anionic trypsin and granulocytic elastase, has been demonstrated in faecal extracts from patients with ulcerative colitis. We wanted to verify that SLPI is actually secreted from normal human colonic mucosa. Also, we wanted to ascertain whether studies of SLPI secretion based on punch biopsies were dependent on biopsy area or on biopsy circumference. Normal colonic mucosa was sampled during surgery for colonic cancer. A total of 36 samples from four patients were used. Mucosa preparation was carried out using a punch biopsy technique, and samples of 3, 4 and 6 mm diameter were used. All media contained SLPI at varying concentrations. When expressed in terms of the sample area, the secretion per millimetre-squared seemed to decrease with increasing area. When calculated as secretion per circumference, secretion seemed to be constant. In conclusion, SLPI was secreted from normal human colonic mucosa. The SLPI secretion seemed dependent on the circumference of the biopsy rather than on the area of the biopsy.

  20. Time- and dose-dependent effects of curcumin on gene expression in human colon cancer cells

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    van Erk Marjan J

    2004-05-01

    Full Text Available Abstract Background Curcumin is a spice and a coloring food compound with a promising role in colon cancer prevention. Curcumin protects against development of colon tumors in rats treated with a colon carcinogen, in colon cancer cells curcumin can inhibit cell proliferation and induce apoptosis, it is an anti-oxidant and it can act as an anti-inflammatory agent. The aim of this study was to elucidate mechanisms and effect of curcumin in colon cancer cells using gene expression profiling. Methods Gene expression changes in response to curcumin exposure were studied in two human colon cancer cell lines, using cDNA microarrays with four thousand human genes. HT29 cells were exposed to two different concentrations of curcumin and gene expression changes were followed in time (3, 6, 12, 24 and 48 hours. Gene expression changes after short-term exposure (3 or 6 hours to curcumin were also studied in a second cell type, Caco-2 cells. Results Gene expression changes (>1.5-fold were found at all time points. HT29 cells were more sensitive to curcumin than Caco-2 cells. Early response genes were involved in cell cycle, signal transduction, DNA repair, gene transcription, cell adhesion and xenobiotic metabolism. In HT29 cells curcumin modulated a number of cell cycle genes of which several have a role in transition through the G2/M phase. This corresponded to a cell cycle arrest in the G2/M phase as was observed by flow cytometry. Functional groups with a similar expression profile included genes involved in phase-II metabolism that were induced by curcumin after 12 and 24 hours. Expression of some cytochrome P450 genes was downregulated by curcumin in HT29 and Caco-2 cells. In addition, curcumin affected expression of metallothionein genes, tubulin genes, p53 and other genes involved in colon carcinogenesis. Conclusions This study has extended knowledge on pathways or processes already reported to be affected by curcumin (cell cycle arrest, phase

  1. Breast Cancer Cell Colonization of the Human Bone Marrow Adipose Tissue Niche

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    Zach S. Templeton

    2015-12-01

    Full Text Available BACKGROUND/OBJECTIVES: Bone is a preferred site of breast cancer metastasis, suggesting the presence of tissue-specific features that attract and promote the outgrowth of breast cancer cells. We sought to identify parameters of human bone tissue associated with breast cancer cell osteotropism and colonization in the metastatic niche. METHODS: Migration and colonization patterns of MDA-MB-231-fLuc-EGFP (luciferase-enhanced green fluorescence protein and MCF-7-fLuc-EGFP breast cancer cells were studied in co-culture with cancellous bone tissue fragments isolated from 14 hip arthroplasties. Breast cancer cell migration into tissues and toward tissue-conditioned medium was measured in Transwell migration chambers using bioluminescence imaging and analyzed as a function of secreted factors measured by multiplex immunoassay. Patterns of breast cancer cell colonization were evaluated with fluorescence microscopy and immunohistochemistry. RESULTS: Enhanced MDA-MB-231-fLuc-EGFP breast cancer cell migration to bone-conditioned versus control medium was observed in 12/14 specimens (P = .0014 and correlated significantly with increasing levels of the adipokines/cytokines leptin (P = .006 and IL-1β (P = .001 in univariate and multivariate regression analyses. Fluorescence microscopy and immunohistochemistry of fragments underscored the extreme adiposity of adult human bone tissues and revealed extensive breast cancer cell colonization within the marrow adipose tissue compartment. CONCLUSIONS: Our results show that breast cancer cells migrate to human bone tissue-conditioned medium in association with increasing levels of leptin and IL-1β, and colonize the bone marrow adipose tissue compartment of cultured fragments. Bone marrow adipose tissue and its molecular signals may be important but understudied components of the breast cancer metastatic niche.

  2. Gamma-Mangostin, a Micronutrient of Mangosteen Fruit, Induces Apoptosis in Human Colon Cancer Cells

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    Hui-Fang Chang

    2012-07-01

    Full Text Available Recently colorectal cancer rates have increased rapidly in Taiwan. The treatment of colorectal cancer includes surgery, radiation therapy and chemotherapy. Mangosteen (Garcinia mangostana is a famous Asian tropical fruit. γ-Mangostin is a xanthone derivative isolated from the fruit hull. In previous studies, we found evidence of anti-inflammatory and anti-brain tumor activities in γ-mangostin. In this study, we performed further studies to assess the apoptotic effects of γ-mangostin on colorectal adenocarcinoma cells HT29. γ-Mangostin showed concentration and time-dependent cytotoxic effects on HT29 cells. Microscopic observation under Giemsa staining showed that γ-mangostin induced cellular swelling and the appearance of apoptotic bodies, characteristic of apoptosis in HT29 cells. In addition, flow cytometry analysis showed an increase of hypodiploid cells in γ-mangostin-treated HT29 cells, while enhancement of intracellular peroxide production was detected in the same γ-mangostin-treated cells by DCHDA assay and DiOC6(3 staining. In view of the above results, γ-mangostin has demonstrated anticancer activity and induces apoptosis in HT29 colorectal adenocarcinoma cells. The evidence suggests that γ-mangostin could serve as a micronutrient for colon cancer prevention and is a potential lead compound for the development of anti-colon cancer agents.

  3. Zinc-pheophorbide a-highly efficient low-cost photosensitizer against human adenocarcinoma in cellular and animal models.

    Science.gov (United States)

    Jakubowska, Monika; Szczygieł, Małgorzata; Michalczyk-Wetula, Dominika; Susz, Anna; Stochel, Grażyna; Elas, Martyna; Fiedor, Leszek; Urbanska, Krystyna

    2013-09-01

    Our previous study has shown a prolonged retention and accumulation of Zn-pheophorbide a, a water-soluble derivative of chlorophyll a, in tumor tissue (Szczygiel et al. [19]). This prompted us to further evaluate the phototherapeutic potential of this photosensitizer of excellent physicochemical properties. Cellular uptake of Zn-pheophorbide, its localization in cells, cytotoxicity, phototoxicity and cell death mechanisms were studied in human adenocarcinoma cell lines: A549, MCF-7 and LoVo. The PDT efficacy was tested against A549 tumors growing in nude mice. Zn-pheophorbide a even at very low concentrations (∼1×10(-6)M) and at low light doses (5J/cm(2)) causes a strong photodynamic effect, leading to 100% cell mortality. Confocal microscopy showed that in contrast to most derivatives of chlorophyll, Zn-pheophorbide a does not localize to mitochondria. The photodynamic effects and the cell death mechanisms of Zn-pheophorbide a, its Mg analog (chlorophyllide a) and Photofrin were compared on the A549 cells. Zn-pheophorbide a showed the strongest photodynamic effect, at low dose killing all A549 cells via apoptosis and necrosis. The very high anti-cancer potential of Zn-pheophorbide was confirmed in a photodynamic treatment of the A549 tumors. They either regressed or were markedly inhibited for up to 4 months after the treatment, resulting, on average, in a 5-fold decrease in tumor volume. These results show that Zn-pheophorbide a is a very promising low-cost, synthetically easily accessible, second generation photosensitizer against human cancer. Copyright © 2013 Elsevier B.V. All rights reserved.

  4. Identification of the Virulence Landscape Essential for Entamoeba histolytica Invasion of the Human Colon

    Science.gov (United States)

    Hon, Chung-Chau; Dillies, Marie-Agnès; Avé, Patrick; Coppée, Jean-Yves; Labruyère, Elisabeth; Guillén, Nancy

    2013-01-01

    Entamoeba histolytica is the pathogenic amoeba responsible for amoebiasis, an infectious disease targeting human tissues. Amoebiasis arises when virulent trophozoites start to destroy the muco-epithelial barrier by first crossing the mucus, then killing host cells, triggering inflammation and subsequently causing dysentery. The main goal of this study was to analyse pathophysiology and gene expression changes related to virulent (i.e. HM1:IMSS) and non-virulent (i.e. Rahman) strains when they are in contact with the human colon. Transcriptome comparisons between the two strains, both in culture conditions and upon contact with human colon explants, provide a global view of gene expression changes that might contribute to the observed phenotypic differences. The most remarkable feature of the virulent phenotype resides in the up-regulation of genes implicated in carbohydrate metabolism and processing of glycosylated residues. Consequently, inhibition of gene expression by RNA interference of a glycoside hydrolase (β-amylase absent from humans) abolishes mucus depletion and tissue invasion by HM1:IMSS. In summary, our data suggest a potential role of carbohydrate metabolism in colon invasion by virulent E. histolytica. PMID:24385905

  5. Light- and electron microscopical studies of interstitial cells of Cajal and muscle cells at the submucosal border of human colon

    DEFF Research Database (Denmark)

    Rumessen, J J; Peters, S; Thuneberg, L

    1993-01-01

    It has been suggested that interstitial cells of Cajal (ICC) at the submucosal border of the colonic circular muscle are pacemaker cells. We studied smooth muscle cells and ICC at the submucosal surface of the circular muscle layer of the normal human colon....

  6. Promoter hypermethylation mediated downregulation of FBP1 in human hepatocellular carcinoma and colon cancer.

    Directory of Open Access Journals (Sweden)

    Mingquan Chen

    Full Text Available FBP1, fructose-1,6-bisphosphatase-1, a gluconeogenesis regulatory enzyme, catalyzes the hydrolysis of fructose 1,6-bisphosphate to fructose 6-phosphate and inorganic phosphate. The mechanism that it functions to antagonize glycolysis and was epigenetically inactivated through NF-kappaB pathway in gastric cancer has been reported. However, its role in the liver carcinogenesis still remains unknown. Here, we investigated the expression and DNA methylation of FBP1 in primary HCC and colon tumor. FBP1 was lowly expressed in 80% (8/10 human hepatocellular carcinoma, 66.7% (6/9 liver cancer cell lines and 100% (6/6 colon cancer cell lines, but was higher in paired adjacent non-tumor tissues and immortalized normal cell lines, which was well correlated with its promoter methylation status. Methylation was further detected in primary HCCs, gastric and colon tumor tissues, but none or occasionally in paired adjacent non-tumor tissues. Detailed methylation analysis of 29 CpG sites at a 327-bp promoter region by bisulfite genomic sequencing confirmed its methylation. FBP1 silencing could be reversed by chemical demethylation treatment with 5-aza-2'-deoxycytidine (Aza, indicating direct epigenetic silencing. Restoring FBP1 expression in low expressed cells significantly inhibited cell growth and colony formation ability through the induction of G2-M phase cell cycle arrest. Moreover, the observed effects coincided with an increase in reactive oxygen species (ROS generation. In summary, epigenetic inactivation of FBP1 is also common in human liver and colon cancer. FBP1 appears to be a functional tumor suppressor involved in the liver and colon carcinogenesis.

  7. Colonization of plants by human pathogenic bacteria in the course of organic vegetable production

    Directory of Open Access Journals (Sweden)

    Andreas eHofmann

    2014-05-01

    Full Text Available In recent years, increasing numbers of outbreaks caused by the consumption of vegetables contaminated with human pathogenic bacteria were reported. The application of organic fertilizers during vegetable production is one of the possible reasons for contamination with those pathogens. In this study laboratory experiments in axenic and soil systems following common practices in organic farming were conducted to identify the minimal dose needed for bacterial colonization of plants and to identify possible factors like bacterial species or serovariation, plant species or organic fertilizer types used, influencing the success of plant colonization by human pathogenic bacteria. Spinach and corn salad were chosen as model plants and were inoculated with different concentrations of Salmonella enterica sv. Weltevreden, Listeria monocytogenes sv. 4b and EGD-E sv. 1/2a either directly (axenic system or via agricultural soil amended with spiked organic fertilizers (soil system. In addition to PCR- and culture-based detection methods, fluorescence in situ hybridization (FISH was applied in order to localize bacteria on or in plant tissues. Our results demonstrate that shoots were colonized by the pathogenic bacteria at inoculation doses as low as 4x10CFU/ml in the axenic system or 4x105CFU/g in the soil system. In addition, plant species dependent effects were observed. Spinach was colonized more often and at lower inoculation doses compared to corn salad. Differential colonization sites on roots, depending on the plant species could be detected using FISH-CLSM analysis. Furthermore, the transfer of pathogenic bacteria to plants via organic fertilizers was observed more often and at lower initial inoculation doses when fertilization was performed with inoculated slurry compared to inoculated manure. Finally, it could be shown that by introducing a simple washing step, the bacterial contamination was reduced in most cases or even was removed completely in

  8. Colonization of plants by human pathogenic bacteria in the course of organic vegetable production

    Science.gov (United States)

    Hofmann, Andreas; Fischer, Doreen; Hartmann, Anton; Schmid, Michael

    2014-01-01

    In recent years, increasing numbers of outbreaks caused by the consumption of vegetables contaminated with human pathogenic bacteria were reported. The application of organic fertilizers during vegetable production is one of the possible reasons for contamination with those pathogens. In this study laboratory experiments in axenic and soil systems following common practices in organic farming were conducted to identify the minimal dose needed for bacterial colonization of plants and to identify possible factors like bacterial species or serovariation, plant species or organic fertilizer types used, influencing the success of plant colonization by human pathogenic bacteria. Spinach and corn salad were chosen as model plants and were inoculated with different concentrations of Salmonella enterica sv. Weltevreden, Listeria monocytogenes sv. 4b and EGD-E sv. 1/2a either directly (axenic system) or via agricultural soil amended with spiked organic fertilizers (soil system). In addition to PCR- and culture-based detection methods, fluorescence in situ hybridization (FISH) was applied in order to localize bacteria on or in plant tissues. Our results demonstrate that shoots were colonized by the pathogenic bacteria at inoculation doses as low as 4 × 10 CFU/ml in the axenic system or 4 × 105 CFU/g in the soil system. In addition, plant species dependent effects were observed. Spinach was colonized more often and at lower inoculation doses compared to corn salad. Differential colonization sites on roots, depending on the plant species could be detected using FISH-CLSM analysis. Furthermore, the transfer of pathogenic bacteria to plants via organic fertilizers was observed more often and at lower initial inoculation doses when fertilization was performed with inoculated slurry compared to inoculated manure. Finally, it could be shown that by introducing a simple washing step, the bacterial contamination was reduced in most cases or even was removed completely in some cases

  9. Dietary pectic glycans are degraded by coordinated enzyme pathways in human colonic Bacteroides

    DEFF Research Database (Denmark)

    Luis, Ana S.; Briggs, Jonathon; Zhang, Xiaoyang

    2018-01-01

    utilization loci (PULs). In Bacteroides thetaiotaomicron, a human colonic bacterium, the PULs activated by different pectin domains have been identified; however, the mechanism by which these loci contribute to the degradation of these GalA-containing polysaccharides is poorly understood. Here we show......The major nutrients available to human colonic Bacteroides species are glycans, exemplified by pectins, a network of covalently linked plant cell wall polysaccharides containing galacturonic acid (GalA). Metabolism of complex carbohydrates by the Bacteroides genus is orchestrated by polysaccharide...... PULs ensuring a continuous supply of inducing molecules throughout growth. The contribution of Bacteroides spp. to metabolism of the pectic network is illustrated by cross-feeding between organisms....

  10. Lipase member H is a novel secreted protein selectively upregulated in human lung adenocarcinomas and bronchioloalveolar carcinomas

    Energy Technology Data Exchange (ETDEWEB)

    Seki, Yasuhiro [Graduate School of Arts and Sciences, The University of Tokyo, Tokyo (Japan); Research Center for Stem Cell Engineering, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba (Japan); Yoshida, Yukihiro [Department of Surgery, Asahi General Hospital, Chiba (Japan); Department of Thoracic Surgery, The University of Tokyo, Graduate School of Medicine, Tokyo (Japan); Ishimine, Hisako [Research Center for Stem Cell Engineering, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba (Japan); Graduate School of Life and Environmental Sciences, The University of Tsukuba, Tsukuba, Ibaraki (Japan); Shinozaki-Ushiku, Aya [Department of Pathology, Graduate School of Medicine, The University of Tokyo, Hongo, Tokyo (Japan); Ito, Yoshimasa [Research Center for Stem Cell Engineering, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba (Japan); Sumitomo, Kenya [Department of Internal Medicine, JA Kochi Hospital, Kochi (Japan); Nakajima, Jun [Department of Thoracic Surgery, The University of Tokyo, Graduate School of Medicine, Tokyo (Japan); Fukayama, Masashi [Department of Pathology, Graduate School of Medicine, The University of Tokyo, Hongo, Tokyo (Japan); Michiue, Tatsuo [Graduate School of Arts and Sciences, The University of Tokyo, Tokyo (Japan); Asashima, Makoto, E-mail: asashi@bio.c.u-tokyo.ac.jp [Graduate School of Arts and Sciences, The University of Tokyo, Tokyo (Japan); Research Center for Stem Cell Engineering, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba (Japan); Life Science Center of Tsukuba Advanced Research Alliance (TARA), The University of Tsukuba, Tsukuba, Ibaraki (Japan); Kurisaki, Akira, E-mail: akikuri@hotmail.com [Research Center for Stem Cell Engineering, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba (Japan); Graduate School of Life and Environmental Sciences, The University of Tsukuba, Tsukuba, Ibaraki (Japan)

    2014-01-24

    Highlights: • Most of the adenocarcinomas and bronchioloalveolar carcinomas were LIPH-positive. • LIPH is necessary for the proliferation of lung cancer cells in vitro. • A high level of LIPH in serum is correlated with better survival in early phase lung-cancer patients after surgery. - Abstract: Lung cancer is one of the most frequent causes of cancer-related death worldwide. However, molecular markers for lung cancer have not been well established. To identify novel genes related to lung cancer development, we surveyed publicly available DNA microarray data on lung cancer tissues. We identified lipase member H (LIPH, also known as mPA-PLA1) as one of the significantly upregulated genes in lung adenocarcinoma. LIPH was expressed in several adenocarcinoma cell lines when they were analyzed by quantitative real-time polymerase chain reaction (qPCR), western blotting, and sandwich enzyme-linked immunosorbent assay (ELISA). Immunohistochemical analysis detected LIPH expression in most of the adenocarcinomas and bronchioloalveolar carcinomas tissue sections obtained from lung cancer patients. LIPH expression was also observed less frequently in the squamous lung cancer tissue samples. Furthermore, LIPH protein was upregulated in the serum of early- and late-phase lung cancer patients when they were analyzed by ELISA. Interestingly, high serum level of LIPH was correlated with better survival in early phase lung cancer patients after surgery. Thus, LIPH may be a novel molecular biomarker for lung cancer, especially for adenocarcinoma and bronchioloalveolar carcinoma.

  11. Optical properties of human colon tissues in the 350 – 2500 nm spectral range

    Energy Technology Data Exchange (ETDEWEB)

    Bashkatov, A N; Genina, E A; Kochubey, V I; Kolesnikova, E A; Tuchin, V V [N.G. Chernyshevsky Saratov State University, Saratov (Russian Federation); Rubtsov, V S [V.I.Razumovsky Saratov State Medical University, Saratov (Russian Federation)

    2014-08-31

    We present the optical characteristics of the mucosa and submucosa of human colon tissue. The experiments are performed in vitro using a LAMBDA 950 spectrophotometer in the 350 – 2500 nm spectral range. The absorption and scattering coefficients and the scattering anisotropy factor are calculated based on the measured diffuse reflectance and total and collimated transmittance spectra using the inverse Monte Carlo method. (laser biophotonics)

  12. Extracts of Opuntia humifusa Fruits Inhibit the Growth of AGS Human Gastric Adenocarcinoma Cells

    OpenAIRE

    Hahm, Sahng-Wook; Park, Jieun; Park, Kun-Young; Son, Yong-Suk; Han, Hyungchul

    2016-01-01

    Opuntia humifusa (OHF) has been used as a nutraceutical source for the prevention of chronic diseases. In the present study, the inhibitory effects of ethyl acetate extracts of OHF on the proliferation of AGS human gastric cancer cells and the mode of action were investigated. To elucidate the antiproliferative mechanisms of OHF in cancer cells, the expression of genes related to apoptosis and cell cycle arrest were determined with real-time PCR and western blot. The cytotoxic effect of OHF o...

  13. Evaluation of physicochemical properties and intestinal permeability of six dietary polyphenols in human intestinal colon adenocarcinoma Caco-2 cells.

    Science.gov (United States)

    Rastogi, Himanshu; Jana, Snehasis

    2016-02-01

    Phenolic compounds are common ingredients in many dietary supplements and functional foods. However, data concerning physicochemical properties and permeability of polyphenols on the intestinal epithelial cells are scarce. The aims of this study were to determine the experimental partition coefficient (Log P), and parallel artificial membrane permeability assay (PAMPA), to characterize the bi-directional transport of six phenolic compounds viz. caffeic acid, chrysin, gallic acid, quercetin, resveratrol and rutin in Caco-2 cells. The experimental Log P values of six polyphenols were correlated (R (2) = 0.92) well with the calculated Log P values. The apparent permeability (P app) range of all polyphenols in PAMPA for the apical (AP) to basolateral (BL) was 1.18 ± 0.05 × 10(-6) to 5.90 ± 0.16 × 10(-6) cm/s. The apparent Caco-2 permeability (P app) range for the AP-BL was 0.96 ± 0.03 × 10(-6) to 3.80 ± 0.45 × 10(-6) cm/s. The efflux ratio of P app (BL → AP) to P app (AP → BL) for all phenolics was Caco-2 cell monolayer permeation data. Dietary six polyphenols were poorly absorbed through PAMPA and Caco-2 cells, and their transepithelial transports were mainly by passive diffusion.

  14. Depletion of mitochondrial fission factor DRP1 causes increased apoptosis in human colon cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Inoue-Yamauchi, Akane, E-mail: ainoyama@research.twmu.ac.jp [Department of Pathology, Tokyo Women' s Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo 162-8666 (Japan); Oda, Hideaki [Department of Pathology, Tokyo Women' s Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo 162-8666 (Japan)

    2012-04-27

    Highlights: Black-Right-Pointing-Pointer DRP1 is required for mitochondrial fission in colon cancer cells. Black-Right-Pointing-Pointer DRP1 participates in inhibition of colon cancer cell apoptosis. Black-Right-Pointing-Pointer DRP1 can inhibit apoptosis through the regulation of cytochrome c release. -- Abstract: Mitochondria play a critical role in regulation of apoptosis, a form of programmed cell death, by releasing apoptogenic factors including cytochrome c. Growing evidence suggests that dynamic changes in mitochondrial morphology are involved in cellular apoptotic response. However, whether DRP1-mediated mitochondrial fission is required for induction of apoptosis remains speculative. Here, we show that siRNA-mediated DRP1 knockdown promoted accumulation of elongated mitochondria in HCT116 and SW480 human colon cancer cells. Surprisingly, DRP1 down-regulation led to decreased proliferation and increased apoptosis of these cells. A higher rate of cytochrome c release and reductions in mitochondrial membrane potential were also revealed in DRP1-depleted cells. Taken together, our present findings suggest that mitochondrial fission factor DRP1 inhibits colon cancer cell apoptosis through the regulation of cytochrome c release and mitochondrial membrane integrity.

  15. Oestrogen inhibits human colonic motility by a non-genomic cell membrane receptor-dependent mechanism.

    LENUS (Irish Health Repository)

    Hogan, A M

    2012-02-01

    BACKGROUND: Classical effects of oestrogen involve activation of target genes after binding nuclear receptors. Oestrogenic effects too rapid for DNA transcription (non-genomic) are known to occur. The effect of oestrogen on colonic motility is unknown despite the prevalence of gastrointestinal symptoms in pregnant and premenopausal women. METHODS: Histologically normal colon was obtained from proximal resection margins of colorectal carcinoma specimens. Circular smooth muscle strips were microdissected and suspended in organ baths under 1 g of tension. After equilibration, they were exposed to 17beta-oestradiol (n = 8) or bovine serum albumin (BSA)-conjugated 17beta-oestradiol (n = 8). Fulvestrant, an oestrogen receptor antagonist, was added to some baths (n = 8). Other strips were exposed to calphostin C or cycloheximide. Carbachol was added in increasing concentrations and contractile activity was recorded isometrically. RESULTS: Oestrogen inhibited colonic contractility (mean difference 19.7 per cent; n = 8, P < 0.001). In keeping with non-genomic, rapid-onset steroid action, the effect was apparent within minutes and reversible. It was observed with both 17beta-oestradiol and BSA-conjugated oestrogen, and was not altered by cycloheximide. Effects were inhibited by fulvestrant, suggesting receptor mediation. CONCLUSION: Oestrogen decreases contractility in human colonic smooth muscle by a non-genomic mechanism involving cell membrane coupling.

  16. MicroRNA profiling in human colon cancer cells during 5-fluorouracil-induced autophagy.

    Directory of Open Access Journals (Sweden)

    Ni Hou

    Full Text Available Autophagy modulation is now recognized as a potential therapeutic approach for cancer (including colorectal cancer, yet the molecular mechanisms regulating autophagy in response to cellular stress are still not well understood. MicroRNAs (miRNAs have been found to play important roles in controlling many cellular functions, including growth, metabolism and stress response. The physiological importance of the miRNA-autophagy interconnection is only beginning to be elucidated. MiRNA microarray technology facilitates analysis of global miRNA expression in certain situations. In this study, we explored the expression profile of miRNAs during the response of human colon cancer cells (HT29s to 5-FU treatment and nutrient starvation using miRNA microarray analysis. The alteration of miRNA expression showed the same pattern under both conditions was further testified by qRT-PCR in three human colon cancer cell lines. In addition, bioinformatic prediction of target genes, pathway analysis and gene network analysis were performed to better understand the roles of these miRNAs in the regulation of autophagy. We identified and selected four downregulated miRNAs including hsa-miR-302a-3p and 27 upregulated miRNAs under these two conditions as having the potential to target genes involved in the regulation of autophagy in human colon cancer cells. They have the potential to modulate autophagy in 5-FU-based chemotherapy in colorectal cancer.

  17. Detection of human papillomavirus infection by molecular tests and its relation to colonic polyps and colorectal cancer

    Directory of Open Access Journals (Sweden)

    Faten Gazzaz

    2016-03-01

    Full Text Available Objectives: To prospectively examine the association between human papilloma virus (HPV colonization of the colonic mucosa and the development of colorectal polyps (CRPs, and colorectal cancer (CRC in Saudi Arabia. Methods: A case control study was performed between January 2013 and December 2014. All eligible patients underwent standard diagnostic colonoscopy. Patients with polyps or colorectal cancer were considered cases, while those with any other endoscopic findings were controls. Biopsy samples from polyps and tumors, and/or from normal colonic mucosa were acquired. Human papilloma virus colonization was detected using a hybrid capture technique of samples taken from both normal tissue, and CRPs and CRC. The association between HPV and CRPs/CRC was evaluated. Results: A total of 132 patients were recruited. The mean age was 53 (±15.9 years. Sixty patients had endoscopically detectable CRPs/CRC, and 72 had either inflammation or normal endoscopic evaluations. Only 4 (0.8% of the 132 samples that were collected and analyzed were positive for the HPV gene. Statistical analysis did not identify any significant association between HPV colonization and the presence of CRPs/CRC. The only significant predictor of detecting CRPs/CRC on colonoscopy was symptomatic presentation (odds ratio=11.072, 95% confidence interval 4.7-26.2, p<0.001. Conclusion: Human papilloma virus colonic colonization is rare in Saudi Arabia. An association between HPV colonization and CRP/CRC development could not be identified in this cohort of patients.

  18. Colon Cancer Tumorigenesis Initiated by the H1047R Mutant PI3K.

    Directory of Open Access Journals (Sweden)

    Alexander E Yueh

    Full Text Available The phosphoinositide 3-kinase (PI3K signaling pathway is critical for multiple important cellular functions, and is one of the most commonly altered pathways in human cancers. We previously developed a mouse model in which colon cancers were initiated by a dominant active PI3K p110-p85 fusion protein. In that model, well-differentiated mucinous adenocarcinomas developed within the colon and initiated through a non-canonical mechanism that is not dependent on WNT signaling. To assess the potential relevance of PI3K mutations in human cancers, we sought to determine if one of the common mutations in the human disease could also initiate similar colon cancers. Mice were generated expressing the Pik3caH1047R mutation, the analog of one of three human hotspot mutations in this gene. Mice expressing a constitutively active PI3K, as a result of this mutation, develop invasive adenocarcinomas strikingly similar to invasive adenocarcinomas found in human colon cancers. These tumors form without a polypoid intermediary and also lack nuclear CTNNB1 (β-catenin, indicating a non-canonical mechanism of tumor initiation mediated by the PI3K pathway. These cancers are sensitive to dual PI3K/mTOR inhibition indicating dependence on the PI3K pathway. The tumor tissue remaining after treatment demonstrated reduction in cellular proliferation and inhibition of PI3K signaling.

  19. Potential Factors Enabling Human Body Colonization by Animal Streptococcus dysgalactiae subsp. equisimilis Strains.

    Science.gov (United States)

    Ciszewski, Marcin; Szewczyk, Eligia M

    2017-05-01

    Streptococcus dysgalactiae subsp. equisimilis (SDSE) is a pyogenic, Lancefield C or G streptococcal pathogen. Until recently, it has been considered as an exclusive animal pathogen. Nowadays, it is responsible for both animal infections in wild animals, pets, and livestock and human infections often clinically similar to the ones caused by group A streptococcus (Streptococcus pyogenes). The risk of zoonotic infection is the most significant in people having regular contact with animals, such as veterinarians, cattlemen, and farmers. SDSE is also prevalent on skin of healthy dogs, cats, and horses, which pose a risk also to people having contact with companion animals. The main aim of this study was to evaluate if there are features differentiating animal and human SDSE isolates, especially in virulence factors involved in the first stages of pathogenesis (adhesion and colonization). Equal groups of human and animal SDSE clinical strains were obtained from superficial infections (skin, wounds, abscesses). The presence of five virulence genes (prtF1, prtF2, lmb, cbp, emm type) was evaluated, as well as ability to form bacterial biofilm and produce BLIS (bacteriocin-like inhibitory substances) which are active against human skin microbiota. The study showed that the presence of genes coding for fibronectin-binding protein and M protein, as well as BLIS activity inhibiting the growth of Corynebacterium spp. strains might constitute the virulence factors which are necessary to colonize human organism, whereas they are not crucial in animal infections. Those virulence factors might be horizontally transferred from human streptococci to animal SDSE strains, enabling their ability to colonize human organism.

  20. Lycopene Inhibits Metastasis of Human Liver Adenocarcinoma SK-Hep-1 Cells by Downregulation of NADPH Oxidase 4 Protein Expression.

    Science.gov (United States)

    Jhou, Bo-Yi; Song, Tuzz-Ying; Lee, Inn; Hu, Miao-Lin; Yang, Nae-Cherng

    2017-08-16

    NADPH oxidase 4 (NOX4), with the sole function to produce reactive oxygen species (ROS), can be a molecular target for disrupting cancer metastasis. Several studies have indicated that lycopene exhibited anti-metastatic actions in vitro and in vivo. However, the role of NOX4 in the anti-metastatic action of lycopene remains unknown. Herein, we first confirmed the anti-metastatic effect of lycopene (0.1-5 μM) on human liver adenocarcinoma SK-Hep-1 cells. We showed that lycopene significantly inhibited NOX4 protein expression, with the strongest inhibition of 64.3 ± 10.2% (P lycopene. Lycopene also significantly inhibited NOX4 mRNA expression, NOX activity, and intracellular ROS levels in SK-Hep-1 cells. We then determined the effects of lycopene on transforming growth factor β (TGF-β)-induced metastasis. We found that TGF-β (5 ng/mL) significantly increased migration, invasion, and adhesion activity, the intracellular ROS level, matrix metalloproteinase 9 (MMP-9) and MMP-2 activities, the level of NOX4 protein expression, and NOX activity. All these TGF-β-induced effects were antagonized by the incubation of SK-Hep-1 cells with lycopene (2.5 μM). Using transient transfection of siRNA against NOX4, we found that the downregulation of NOX4 could mimic lycopene by inhibiting cell migration and the activities of MMP-9 and MMP-2 during the incubation with or without TGF-β on SK-Hep-1 cells. The results demonstrate that the downregulation of NOX4 plays a crucial role in the anti-metastatic action of lycopene in SK-Hep-1 cells.

  1. Therapeutic efficacy evaluation of 111in-VNB-liposome on human colorectal adenocarcinoma HT-29/ luc mouse xenografts

    Science.gov (United States)

    Lee, Wan-Chi; Hwang, Jeng-Jong; Tseng, Yun-Long; Wang, Hsin-Ell; Chang, Ya-Fang; Lu, Yi-Ching; Ting, Gann; Whang-Peng, Jaqueline; Wang, Shyh-Jen

    2006-12-01

    The purpose of this study is to evaluate the therapeutic efficacy of the liposome encaged with vinorelbine (VNB) and 111In-oxine on human colorectal adenocarcinoma (HT-29) using HT-29/ luc mouse xenografts. HT-29 cells stably transfected with plasmid vectors containing luciferase gene ( luc) were transplanted subcutaneously into the male NOD/SCID mice. Biodistribution of the drug was performed when tumor size reached 500-600 mm 3. The uptakes of 111In-VNB-liposome in tumor and normal tissues/organs at various time points postinjection were assayed. Multimodalities, including gamma scintigraphy, bioluminescence imaging (BLI) and whole-body autoradiography (WBAR), were applied for evaluating the therapeutic efficacy when tumor size was about 100 mm 3. The tumor/blood ratios of 111In-VNB-liposome were 0.044, 0.058, 2.690, 20.628 and 24.327, respectively, at 1, 4, 24, 48 and 72 h postinjection. Gamma scinitigraphy showed that the tumor/muscle ratios were 2.04, 2.25 and 4.39, respectively, at 0, 5 and 10 mg/kg VNB. BLI showed that significant tumor control was achieved in the group of 10 mg/kg VNB ( 111In-VNB-liposome). WBAR also confirmed this result. In this study, we have demonstrated a non-invasive imaging technique with a luciferase reporter gene and BLI for evaluation of tumor treatment efficacy in vivo. The SCID mice bearing HT-29/ luc xenografts treated with 111In-VNB-liposome were shown with tumor reduction by this technique.

  2. Determination of optical properties of normal and adenomatous human colon tissues in vitro using integrating sphere techniques

    Science.gov (United States)

    Wei, Hua-Jiang; Xing, Da; Lu, Jian-Jun; Gu, Huai-Min; Wu, Guo-Yong; Jin, Ying

    2005-01-01

    AIM: The purpose of the present study is to compare the optical properties of normal human colon mucosa/submucosa and muscle layer/chorion, and adenomatous human colon mucosa/submucosa and muscle layer/chorion in vitro at 476.5, 488, 496.5, 514.5 and 532 nm. We believe these differences in optical properties should help differential diagnosis of human colon tissues by using optical methods. METHODS: In vitro optical properties were investigated for four kinds of tissues: normal human colon mucosa/submucosa and muscle layer/chorion, and adenomatous human colon mucosa/submucosa and muscle layer/chorion. Tissue samples were taken from 13 human colons (13 adenomatous, 13 normal). From the normal human colons a total of 26 tissue samples, with a mean thickness of 0.40 mm, were used (13 from mucosa/submucosa and 13 from muscle layer/chorion), and from the adenomatous human bladders a total of 26 tissue samples, with a mean thickness of 0.40 mm, were used (13 from mucosa/submucosa and 13 from muscle layer/chorion). The measurements were performed using a double-integrating-sphere setup and the optical properties were assessed from these measurements using the adding-doubling method that was considered reliable. RESULTS: The results of measurement showed that there were significant differences in the absorption coefficients and scattering coefficients between normal and adenomatous human colon mucosa/submucosa at the same wavelength, and there were also significant differences in the two optical parameters between both colon muscle layer/chorion at the same wavelength. And there were large differences in the anisotropy factors between both colon mucosa/submucosa at the same wavelength, there were also large differences in the anisotropy factors between both colon muscle layer/chorion at the same wavelength. There were large differences in the value ranges of the absorption coefficients, scattering coefficients and anisotropy factors between both colon mucosa/submucosa, and

  3. Extracts of Opuntia humifusa Fruits Inhibit the Growth of AGS Human Gastric Adenocarcinoma Cells.

    Science.gov (United States)

    Hahm, Sahng-Wook; Park, Jieun; Park, Kun-Young; Son, Yong-Suk; Han, Hyungchul

    2016-03-01

    Opuntia humifusa (OHF) has been used as a nutraceutical source for the prevention of chronic diseases. In the present study, the inhibitory effects of ethyl acetate extracts of OHF on the proliferation of AGS human gastric cancer cells and the mode of action were investigated. To elucidate the antiproliferative mechanisms of OHF in cancer cells, the expression of genes related to apoptosis and cell cycle arrest were determined with real-time PCR and western blot. The cytotoxic effect of OHF on AGS cells was observed in a dose-dependent manner. Exposure to OHF (100 μg/mL) significantly induced (Pgenes associated with cell cycle progression (Cdk4, Cdk2, and cyclin E) was significantly downregulated (P<0.05) by the OHF treatment. Moreover, the expression of Bax and caspase-3 in OHF treated cells was higher (P<0.05) than in the control. These findings suggest that OHF induces the G1 phase cell cycle arrest and activation of mitochondria-mediated apoptosis pathway in AGS human gastric cancer cells.

  4. LFG-500, a novel synthetic flavonoid, suppresses epithelial-mesenchymal transition in human lung adenocarcinoma cells by inhibiting NLRP3 in inflammatory microenvironment.

    Science.gov (United States)

    Yang, Dan; Cao, Xin; Wang, Fan; Jiang, Haijing; Feng, Dingding; Guo, Hao; Du, Lei; Jin, Yingliang; Chen, Yansu; Yin, Xiaoxing; Li, Chenglin

    2017-08-01

    Increasing evidence indicates that inflammatory microenvironment facilitates tumor metastasis. Here, we found that LFG-500, a novel synthetic flavonoid, significantly inhibited epithelial-mesenchymal transition (EMT) in human lung adenocarcinoma A549 and H1299 cells co-cultured with LPS-challenged THP-1 cells or cultured in THP-1 cell-derived conditioned medium. Moreover, we found that TNF-α is a direct and decisive factor for promoting EMT and LFG-500 suppressed TNF-α-induced EMT and cell motility. NLRP3 knockdown inactivated NLRP3 inflammasome, which subsequently inhibited EMT and blocked cell migration, indicating that TNF-α-induced EMT requires the NLRP3 inflammasome. LFG-500 inhibited the activation of the NLRP3 inflammasome, thus inhibiting EMT. Moreover, LFG-500 treatment significantly inhibited metastasis in vivo by downregulating NLRP3 expression. Importantly, we found that NLRP3 was highly expressed in high-grade lung adenocarcinoma and that its expression was correlated with lymph node metastasis. NLRP3 and vimentin levels were significantly increased in matched metastatic lymph nodes. Moreover, a significant positive correlation was observed between their levels. Together, these results suggest that LFG-500 markedly suppresses EMT by inhibiting the NLRP3 inflammasome in the inflammatory microenvironment and that NLRP3 is a potential biomarker of lung adenocarcinoma metastasis. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. A cross sectional study of animal and human colonization with Methicillin-Resistant Staphylococcus aureus (MRSA) in an Aboriginal community.

    Science.gov (United States)

    Daley, Peter; Bajgai, Janak; Penney, Carla; Williams, Karen; Whitney, Hugh; Golding, George R; Weese, Scott

    2016-07-19

    Methicillin-resistant Staphylococcus aureus (MRSA) infections are common among humans in Aboriginal communities in Canada, for unknown reasons. Cross sectional study of humans and dogs in an Aboriginal community of approximately 1200 persons. Our objectives were to measure community-based prevalence of nasal MRSA colonization among humans, use multivariable logistic regression to analyze risk factors for MRSA colonization, and perform molecular typing of Staphylococci isolated to investigate interspecies transmission. 461 humans were approached for consent and 442 provided complete data. 109/442 (24.7 %, 95 % C.I. = 20.7-28.7 %) of humans were colonized with MRSA. 169/442 (38.2 %) of humans had received antibiotics in the last 12 months. Only number of rooms in the house (OR 0.86, p = 0.023) and recreational dog use (OR 7.7, p = 0.002) were significant risk factors for MRSA colonization. 95/109 (87.1 %) of MRSA strains from humans were of the same spa type (CMRSA10/USA300). 8/157 (5.1 %, 95 % C.I. = 1.7-8.5 %) of dogs were colonized with methicillin-susceptible S. aureus, and no dogs were colonized with MRSA. Human MRSA colonization in this community is very common, and a single clone is predominant, suggesting local transmission. Antibiotic use is also very common. Crowding may partially explain high colonization, but most considered risk factors including animal exposure were not predictive. Very few dogs carried human Staphylococcal strains.

  6. A cross sectional study of animal and human colonization with Methicillin-Resistant Staphylococcus aureus (MRSA in an Aboriginal community

    Directory of Open Access Journals (Sweden)

    Peter Daley

    2016-07-01

    Full Text Available Abstract Background Methicillin-resistant Staphylococcus aureus (MRSA infections are common among humans in Aboriginal communities in Canada, for unknown reasons. Methods Cross sectional study of humans and dogs in an Aboriginal community of approximately 1200 persons. Our objectives were to measure community-based prevalence of nasal MRSA colonization among humans, use multivariable logistic regression to analyze risk factors for MRSA colonization, and perform molecular typing of Staphylococci isolated to investigate interspecies transmission. Results 461 humans were approached for consent and 442 provided complete data. 109/442 (24.7 %, 95 % C.I. = 20.7–28.7 % of humans were colonized with MRSA. 169/442 (38.2 % of humans had received antibiotics in the last 12 months. Only number of rooms in the house (OR 0.86, p = 0.023 and recreational dog use (OR 7.7, p = 0.002 were significant risk factors for MRSA colonization. 95/109 (87.1 % of MRSA strains from humans were of the same spa type (CMRSA10/USA300. 8/157 (5.1 %, 95 % C.I. = 1.7–8.5 % of dogs were colonized with methicillin-susceptible S. aureus, and no dogs were colonized with MRSA. Conclusions Human MRSA colonization in this community is very common, and a single clone is predominant, suggesting local transmission. Antibiotic use is also very common. Crowding may partially explain high colonization, but most considered risk factors including animal exposure were not predictive. Very few dogs carried human Staphylococcal strains.

  7. Effect of Age on the Enteric Nervous System of the Human Colon

    Science.gov (United States)

    Bernard, Cheryl E.; Gibbons, Simon J.; Gomez-Pinilla, Pedro J.; Lurken, Matthew S.; Schmalz, Philip F.; Roeder, Jaime L.; Linden, David; Cima, Robert R.; Dozois, Eric J.; Larson, David W.; Camilleri, Michael; Zinsmeister, Alan R; Pozo, Maria J; Hicks, Gareth A.; Farrugia, Gianrico

    2009-01-01

    The effect of age on the anatomy and function of the human colon is incompletely understood. The prevalence of disorders in adults such as constipation increase with age but it is unclear if this is due to confounding factors or age-related structural defects. The aim of this study was to determine number and subtypes of enteric neurons and neuronal volumes in the human colon of different ages. Normal colon (descending and sigmoid) from 16 patients (9 male) was studied; ages 33–99. Antibodies to HuC/D, ChAT, nNOS, and PGP9.5 were used. Effect of age was determined by testing for linear trends using regression analysis. In the myenteric plexus, number of Hu-positive neurons declined with age (slope = −1.3 neurons/mm/10yrs, p =0.03). The number of ChAT-positive neurons also declined with age (slope = −1.1 neurons/mm/10yrs of age, p=0.02). The number of nNOS-positive neurons did not decline with age. As a result, the ratio of nNOS to Hu increased (slope= 0.03 per 10yrs of age, p=0.01). In the submucosal plexus, the number of neurons did not decline with age (slope = − 0.3 neurons/mm/10 yrs, p =0.09). Volume of nerve fibers in the circular muscle and volume of neuronal structures in the myenteric plexus did not change with age. In conclusion, the number of neurons in the human colon declines with age with sparing of nNOS- positive neurons. This change was not accompanied by changes in total volume of neuronal structures suggesting compensatory changes in the remaining neurons. PMID:19220755

  8. Yes-Associated Protein Expression Is Correlated to the Differentiation of Prostate Adenocarcinoma

    Directory of Open Access Journals (Sweden)

    Myung-Giun Noh

    2017-07-01

    Full Text Available Background Yes-associated protein (YAP in the Hippo signaling pathway is a growth control pathway that regulates cell proliferation and stem cell functions. Abnormal regulation of YAP was reported in human cancers including liver, lung, breast, skin, colon, and ovarian cancer. However, the function of YAP is not known in prostate adenocarcinoma. The purpose of this study was to investigate the role of YAP in tumorigenesis, differentiation, and prognosis of prostate adenocarcinoma. Methods The nuclear and cytoplasmic expression of YAP was examined in 188 cases of prostate adenocarcinoma using immunohistochemistry. YAP expression levels were evaluated in the nucleus and cytoplasm of the prostate adenocarcinoma and the adjacent normal prostate tissue. The presence of immunopositive tumor cells was evaluated and interpreted in comparison with the patients’ clinicopathologic data. Results YAP expression levels were not significantly different between normal epithelial cells and prostate adenocarcinoma. However, YAP expression level was significantly higher in carcinomas with a high Gleason grades (8–10 than in carcinomas with a low Gleason grades (6–7 (p < .01. There was no statistical correlation between YAP expression and stage, age, prostate-specific antigen level, and tumor volume. Biochemical recurrence (BCR–free survival was significantly lower in patients with high YAP expressing cancers (p = .02. However high YAP expression was not an independent prognostic factor for BCR in the Cox proportional hazards model. Conclusions The results suggested that YAP is not associated with prostate adenocarcinoma development, but it may be associated with the differentiation of the adenocarcinoma. YAP was not associated with BCR.

  9. Bax translocation into mitochondria during dihydroartemisinin(DHA)-induced apoptosis in human lung adenocarcinoma cells

    Science.gov (United States)

    Lu, Ying-ying; Chen, Tong-sheng; Qu, Jun-Le

    2009-02-01

    Dihydroartemisinin (DHA), a semi-synthetic derivative of artemisinin, isolated from the traditional Chinese herb Artemisia annua, has been shown to possess promising anticancer activities and induce cancer cell death through apoptotic pathways. However, the molecular mechanisms are not well understood. This study was investigated in human lung adenocarconoma ASTC-a-1 cell line and aimed to determine whether the apoptotic process was mediated by Bax activation and translocation during DHA-induced apoptosis. In this study, DHA induced a time-dependent apoptotic cell death, which was assayed by Cell Counting Kit (CCK-8) and Hoechst 33258 staining. Detection of Bax aggregation and translocation to mitochondria was observed in living cells which were co-transfected with GFP-Bax and Dsred-mito plasmid using confocal fluorescence microscope technique. Overall, these results demonstrated that Bax activation and translocation to mitochondria occurred during DHA-induced apoptosis.

  10. Human Endometrial Adenocarcinoma Transplanted into Nude Mice: Growth Regulation by Estradiol

    Science.gov (United States)

    Satyaswaroop, P. G.; Zaino, R. J.; Mortel, R.

    1983-01-01

    A model for studying the growth of primary tumors of human endometrium and its regulation by 17β -estradiol has been developed in which ovariectomized nude mice are used as recipients. The receptors for sex steroids are maintained during serial transplantation of the tumor in this system. Although the rate of growth of receptor-negative endometrial tumors transplanted into ovariectomized nude mice is unaffected by the sustained presence or absence of estradiol, the growth of receptor-positive tumors is significantly increased by estradiol. Receptor-positive tumors treated with estradiol produced elevated concentrations of progesterone receptor. That the progesterone receptor is functional in this tumor is evident from the induction of estradiol 17β -dehydrogenase activity upon progestin administration. These findings are consistent with receptor-mediated regulation of growth of endometrial carcinoma.

  11. Human milk oligosaccharides shorten rotavirus-induced diarrhea and modulate piglet mucosal immunity and colonic microbiota.

    Science.gov (United States)

    Li, Min; Monaco, Marcia H; Wang, Mei; Comstock, Sarah S; Kuhlenschmidt, Theresa B; Fahey, George C; Miller, Michael J; Kuhlenschmidt, Mark S; Donovan, Sharon M

    2014-08-01

    The impact of human milk oligosaccharides (HMO) on mucosal immunity, gut microbiota and response to rotavirus (RV) infection was investigated in the piglet model. Newborn piglets were fed with formula alone (FF) or formula supplemented with 4 g l(-1) HMO (HMO) or a prebiotic mixture of 9:1 short-chain galactooligosaccharides (3.6 g l(-1)) and long-chain fructooligosaccharides (0.4 g l(-1)) (PRE) (n=19-21 per group) for 15 days. Piglets (n=7-8) in each dietary group were orally infected with porcine rotavirus (RV) OSU strain on d10, and stool consistency was assessed daily. Blood, small intestine and colonic contents were collected at day 15. Serum RV-specific antibody concentrations, intestinal histomorphology, RV non-structural protein-4 (NSP4) and cytokine mRNA expression were assessed. Colonic content pH, dry matter (DM) and short-chain fatty acid concentrations were measured. Ascending colonic microbiota was analyzed by 16S rRNA gene v1-3 region pyrosequencing. HMO- and PRE-fed groups had shorter duration of diarrhea than FF piglets. Infection changed intestinal histomorphology, increased serum RV-specific antibody response and intestinal RV NSP4 expression, and modulated ileal cytokine expression. HMO enhanced T helper type 1 (interferon-gamma) and anti-inflammatory (interleukin-10) cytokines in the ileum, while prebiotics promoted RV-specific immunoglobulin M response to the infection. RV infection and HMO supplementation altered intraluminal environment and gut microbiota. HMO increased pH and lowered DM of colonic contents and enhanced the abundance of unclassified Lachnospiraceae, which contains numerous butyrate-producing bacteria. In conclusion, HMO and prebiotics did not prevent the onset of RV infection but reduced the duration of RV-induced diarrhea in piglets, in part, by modulating colonic microbiota and immune response to RV infection.

  12. Noscapine induces mitochondria-mediated apoptosis in human colon cancer cells in vivo and in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Zi-Rong; Liu, Meng; Peng, Xiu-Lan; Lei, Xiao-Fei; Zhang, Ji-Xiang [Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei Province (China); Dong, Wei-Guo, E-mail: dongwg1966@yahoo.com.cn [Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei Province (China)

    2012-05-11

    Highlights: Black-Right-Pointing-Pointer Noscapine inhibited cell viability of colon cancer in a time- and dose- dependent manner. Black-Right-Pointing-Pointer G{sub 2}/M phase arrest and chromatin condensation and nuclear fragmentation were induced. Black-Right-Pointing-Pointer Noscapine promoted apoptosis via mitochondrial pathways. Black-Right-Pointing-Pointer Tumorigenicity was inhibited by noscapine. -- Abstract: Noscapine, a phthalide isoquinoline alkaloid derived from opium, has been widely used as a cough suppressant for decades. Noscapine has recently been shown to potentiate the anti-cancer effects of several therapies by inducing apoptosis in various malignant cells without any detectable toxicity in cells or tissues. However, the mechanism by which noscapine induces apoptosis in colon cancer cells remains unclear. The signaling pathways by which noscapine induces apoptosis were investigated in colon cancer cell lines treated with various noscapine concentrations for 72 h, and a dose-dependent inhibition of cell viability was observed. Noscapine effectively inhibited the proliferation of LoVo cells in vitro (IC{sub 50} = 75 {mu}M). This cytotoxicity was reflected by cell cycle arrest at G{sub 2}/M and subsequent apoptosis, as indicated by increased chromatin condensation and fragmentation, the upregulation of Bax and cytochrome c (Cyt-c), the downregulation of survivin and Bcl-2, and the activation of caspase-3 and caspase-9. Moreover, in a xenograft tumor model in mice, noscapine injection clearly inhibited tumor growth via the induction of apoptosis, which was demonstrated using a TUNEL assay. These results suggest that noscapine induces apoptosis in colon cancer cells via mitochondrial pathways. Noscapine may be a safe and effective chemotherapeutic agent for the treatment of human colon cancer.

  13. CytoregR inhibits growth and proliferation of human adenocarcinoma cells via induction of apoptosis

    Directory of Open Access Journals (Sweden)

    Hassanhi M

    2006-01-01

    Full Text Available Abstract Background Cancer is one of the devastating neovascular diseases that incapacitate so many people the world over. Recent reports from the National Cancer Institute indicate some significant gain therapy and cancer management as seen in the increase in the 5-year survival rate over the past two decades. Although near-perfect cure rate have been reported in the early-stage disease, these data reveal high recurrence rate and serious side effects including second malignancies and fatalities. Most of the currently used anticancer agents are only effective against proliferating cancer cells. Thus attention has been focused on potential anti-cancer agents capable of killing cancer cells independent of the cell cycle state, to ensure effective elimination of most cancer cells. The objective of this study was to test the chemosensitivity and potential mechanism of action of a novel cancer drug, CytoregR, in a panel of human cancer cells. Methods the study was performed using a series of bioassays including Trypan blue exclusion, MTS Growth inhibition, LDH-cytotoxicity, TUNEL-Terminal DNA fragmentation Apoptosis Assay, and the Caspase protease CPP32 activity assays. Results CytoregR induced significant dose- and time-dependent inhibition of growth in all the cells; with significant differences in chemosensitivity (P < 0.05 between the target cells becoming more apparent at 48 hr exposure. CytoregR showed no significant effect on normal cells relative to the tumor cells. Growth inhibition in all the cells was due to induction of apoptosis at lower concentrations of cytoregR (> 1:300. CytoregR-induced caspase protease-3 (CPP32 activation significantly and positively correlated with apoptosis induction and growth inhibition; thus implicating CPP32 as the principal death pathway in cytoregR-induced apoptosis. Conclusion CytoregR exerted a dose-and time-dependent growth inhibitory effect in all the target cells through induction of apoptosis via the

  14. Modification of the hypoxic fraction of a xenografted human colon tumor by differentiation-inducing agents

    Energy Technology Data Exchange (ETDEWEB)

    Leith, J.T.

    1988-05-18

    Xenografted tumors were produced in nude mice by injection of HCT-15 human colon tumor cells. The hypoxic fractions of control tumors as determined from x-ray survival curves were approximately 18%. Other tumors were treated (every day X 9) with daily injections of N-methylformamide (150 mg/kg) or sodium butyrate (2,000 mg/kg). For both agents, it was found that the hypoxic fractions were less than 0.05% and less than 1.7%, respectively. These data indicate that selected differentiation-inducing agents could be of value for treatment of human solid tumors that contain hypoxic cells.

  15. Superoxide production and expression of NAD(P)H oxidases by transformed and primary human colonic epithelial cells

    DEFF Research Database (Denmark)

    Perner, A; Andresen, Lars; Pedersen, G

    2003-01-01

    Superoxide (O(2)(-)) generation through the activity of reduced nicotinamide dinucleotide (NADH) or reduced nicotinamide dinucleotide phosphate (NADPH) oxidases has been demonstrated in a variety of cell types, but not in human colonic epithelial cells.......Superoxide (O(2)(-)) generation through the activity of reduced nicotinamide dinucleotide (NADH) or reduced nicotinamide dinucleotide phosphate (NADPH) oxidases has been demonstrated in a variety of cell types, but not in human colonic epithelial cells....

  16. Human bone perivascular niche-on-a-chip for studying metastatic colonization.

    Science.gov (United States)

    Marturano-Kruik, Alessandro; Nava, Michele Maria; Yeager, Keith; Chramiec, Alan; Hao, Luke; Robinson, Samuel; Guo, Edward; Raimondi, Manuela Teresa; Vunjak-Novakovic, Gordana

    2018-02-06

    Eight out of 10 breast cancer patients die within 5 years after the primary tumor has spread to the bones. Tumor cells disseminated from the breast roam the vasculature, colonizing perivascular niches around blood capillaries. Slow flows support the niche maintenance by driving the oxygen, nutrients, and signaling factors from the blood into the interstitial tissue, while extracellular matrix, endothelial cells, and mesenchymal stem cells regulate metastatic homing. Here, we show the feasibility of developing a perfused bone perivascular niche-on-a-chip to investigate the progression and drug resistance of breast cancer cells colonizing the bone. The model is a functional human triculture with stable vascular networks within a 3D native bone matrix cultured on a microfluidic chip. Providing the niche-on-a-chip with controlled flow velocities, shear stresses, and oxygen gradients, we established a long-lasting, self-assembled vascular network without supplementation of angiogenic factors. We further show that human bone marrow-derived mesenchymal stem cells, which have undergone phenotypical transition toward perivascular cell lineages, support the formation of capillary-like structures lining the vascular lumen. Finally, breast cancer cells exposed to interstitial flow within the bone perivascular niche-on-a-chip persist in a slow-proliferative state associated with increased drug resistance. We propose that the bone perivascular niche-on-a-chip with interstitial flow promotes the formation of stable vasculature and mediates cancer cell colonization.

  17. Factors that mediate colonization of the human stomach by Helicobacter pylori

    Science.gov (United States)

    Dunne, Ciara; Dolan, Brendan; Clyne, Marguerite

    2014-01-01

    Helicobacter pylori (H. pylori) colonizes the stomach of humans and causes chronic infection. The majority of bacteria live in the mucus layer overlying the gastric epithelial cells and only a small proportion of bacteria are found interacting with the epithelial cells. The bacteria living in the gastric mucus may act as a reservoir of infection for the underlying cells which is essential for the development of disease. Colonization of gastric mucus is likely to be key to the establishment of chronic infection. How H. pylori manages to colonise and survive in the hostile environment of the human stomach and avoid removal by mucus flow and killing by gastric acid is the subject of this review. We also discuss how bacterial and host factors may together go some way to explaining the susceptibility to colonization and the outcome of infection in different individuals. H. pylori infection of the gastric mucosa has become a paradigm for chronic infection. Understanding of why H. pylori is such a successful pathogen may help us understand how other bacterial species colonise mucosal surfaces and cause disease. PMID:24914320

  18. A comparison of linaclotide and lubiprostone dosing regimens on ion transport responses in human colonic mucosa.

    Science.gov (United States)

    Kang, Sang Bum; Marchelletta, Ronald R; Penrose, Harrison; Docherty, Michael J; McCole, Declan F

    2015-03-01

    Linaclotide, a synthetic guanylyl cyclase C (GC-C) agonist, and the prostone analog, Lubiprostone, are approved to manage chronic idiopathic constipation and constipation-predominant irritable bowel syndrome. Lubiprostone also protects intestinal mucosal barrier function in ischemia. GC-C signaling regulates local fluid balance and other components of intestinal mucosal homeostasis including epithelial barrier function. The aim of this study was to compare if select dosing regimens differentially affect linaclotide and lubiprostone modulation of ion transport and barrier properties of normal human colonic mucosa. Normal sigmoid colon biopsies from healthy subjects were mounted in Ussing chambers. Tissues were treated with linaclotide, lubiprostone, or vehicle to determine effects on short-circuit current (I sc). Subsequent I sc responses to the cAMP agonist, forskolin, and the calcium agonist, carbachol, were also measured to assess if either drug caused desensitization. Barrier properties were assessed by measuring transepithelial electrical resistance. I sc responses to linaclotide and lubiprostone were significantly higher than vehicle control when administered bilaterally or to the mucosal side only. Single versus cumulative concentrations of linaclotide showed differences in efficacy while cumulative but not single dosing caused desensitization to forskolin. Lubiprostone reduced forskolin responses under all conditions. Linaclotide and lubiprostone exerted a positive effect on TER that was dependent on the dosing regimen. Linaclotide and lubiprostone increase ion transport responses across normal human colon but linaclotide displays increased sensitivity to the dosing regimen used. These findings may have implications for dosing protocols of these agents in patients with constipation.

  19. Two-photon imaging and spectroscopy of fresh human colon biopsies

    Science.gov (United States)

    Cicchi, R.; Sturiale, A.; Nesi, G.; Tonelli, F.; Pavone, F. S.

    2012-03-01

    Two-photon fluorescence (TPEF) microscopy is a powerful tool to image human tissues up to 200 microns depth without any exogenously added probe. TPEF can take advantage of the autofluorescence of molecules intrinsically contained in a biological tissue, as such NADH, elastin, collagen, and flavins. Two-photon microscopy has been already successfully used to image several types of tissues, including skin, muscles, tendons, bladder. Nevertheless, its usefulness in imaging colon tissue has not been deeply investigated yet. In this work we have used combined two-photon excited fluorescence (TPEF), second harmonic generation microscopy (SHG), fluorescence lifetime imaging microscopy (FLIM), and multispectral two-photon emission detection (MTPE) to investigate different kinds of human ex-vivo fresh biopsies of colon. Morphological and spectroscopic analyses allowed to characterize both healthy mucosa, polyp, and colon samples in a good agreement with common routine histology. Even if further analysis, as well as a more significant statistics on a large number of samples would be helpful to discriminate between low, mild, and high grade cancer, our method is a promising tool to be used as diagnostic confirmation of histological results, as well as a diagnostic tool in a multiphoton endoscope or colonoscope to be used in in-vivo imaging applications.

  20. PKH26 staining defines distinct subsets of normal human colon epithelial cells at different maturation stages.

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    Anna Pastò

    Full Text Available BACKGROUND AND AIM: Colon crypts are characterized by a hierarchy of cells distributed along the crypt axis. Aim of this paper was to develop an in vitro system for separation of epithelial cell subsets in different maturation stages from normal human colon. METHODOLOGY AND MAJOR FINDINGS: Dissociated colonic epithelial cells were stained with PKH26, which allows identification of distinct populations based on their proliferation rate, and cultured in vitro in the absence of serum. The cytofluorimetric expression of CK20, Msi-1 and Lgr5 was studied. The mRNA levels of several stemness-associated genes were also compared in cultured cell populations and in three colon crypt populations isolated by microdissection. A PKH(pos population survived in culture and formed spheroids; this population included subsets with slow (PKH(high and rapid (PKH(low replicative rates. Molecular analysis revealed higher mRNA levels of both Msi-1 and Lgr-5 in PKH(high cells; by cytofluorimetric analysis, Msi-1(+/Lgr5(+ cells were only found within PKH(high cells, whereas Msi-1(+/Lgr5(- cells were also observed in the PKH(low population. As judged by qRT-PCR analysis, the expression of several stemness-associated markers (Bmi-1, EphB2, EpCAM, ALDH1 was highly enriched in Msi-1(+/Lgr5(+ cells. While CK20 expression was mainly found in PKH(low and PKH(neg cells, a small PKH(high subset co-expressed both CK20 and Msi-1, but not Lgr5; cells with these properties also expressed Mucin, and could be identified in vivo in colon crypts. These results mirrored those found in cells isolated from different crypt portions by microdissection, and based on proliferation rates and marker expression they allowed to define several subsets at different maturation stages: PKH(high/Lgr5(+/Msi-1(+/CK20(-, PKH(high/Lgr5(-/Msi-1(+/CK20(+, PKH(low/Lgr5(-/Msi-1(+/Ck20(-, and PKH(low/Lgr5(-/Msi-1(-/CK20(+ cells. CONCLUSIONS: Our data show the possibility of deriving in vitro, without any

  1. Role of ATM in bystander signaling between human monocytes and lung adenocarcinoma cells.

    Science.gov (United States)

    Ghosh, Somnath; Ghosh, Anu; Krishna, Malini

    2015-12-01

    The response of a cell or tissue to ionizing radiation is mediated by direct damage to cellular components and indirect damage mediated by radiolysis of water. Radiation affects both irradiated cells and the surrounding cells and tissues. The radiation-induced bystander effect is defined by the presence of biological effects in cells that were not themselves in the field of irradiation. To establish the contribution of the bystander effect in the survival of the neighboring cells, lung carcinoma A549 cells were exposed to gamma-irradiation, 2Gy. The medium from the irradiated cells was transferred to non-irradiated A549 cells. Irradiated A549 cells as well as non-irradiated A549 cells cultured in the presence of medium from irradiated cells showed decrease in survival and increase in γ-H2AX and p-ATM foci, indicating a bystander effect. Bystander signaling was also observed between different cell types. Phorbol-12-myristate-13-acetate (PMA)-stimulated and gamma-irradiated U937 (human monocyte) cells induced a bystander response in non-irradiated A549 (lung carcinoma) cells as shown by decreased survival and increased γ-H2AX and p-ATM foci. Non-stimulated and/or irradiated U937 cells did not induce such effects in non-irradiated A549 cells. Since ATM protein was activated in irradiated cells as well as bystander cells, it was of interest to understand its role in bystander effect. Suppression of ATM with siRNA in A549 cells completely inhibited bystander effect in bystander A549 cells. On the other hand suppression of ATM with siRNA in PMA stimulated U937 cells caused only a partial inhibition of bystander effect in bystander A549 cells. These results indicate that apart from ATM, some additional factor may be involved in bystander effect between different cell types. Copyright © 2015 Elsevier B.V. All rights reserved.

  2. Ketogenic HMGCS2 Is a c-Myc target gene expressed in differentiated cells of human colonic epithelium and down-regulated in colon cancer.

    Science.gov (United States)

    Camarero, Nuria; Mascaró, Cristina; Mayordomo, Cristina; Vilardell, Felip; Haro, Diego; Marrero, Pedro F

    2006-09-01

    HMGCS2, the gene that regulates ketone body production, is expressed in liver and several extrahepatic tissues, such as the colon. In CaCo-2 colonic epithelial cells, the expression of this gene increases with cell differentiation. Accordingly, immunohistochemistry with specific antibodies shows that HMGCS2 is expressed mainly in differentiated cells of human colonic epithelium. Here, we used a chromatin immunoprecipitation assay to study the molecular mechanism responsible for this expression pattern. The assay revealed that HMGCS2 is a direct target of c-Myc, which represses HMGCS2 transcriptional activity. c-Myc transrepression is mediated by blockade of the transactivating activity of Miz-1, which occurs mainly through a Sp1-binding site in the proximal promoter of the gene. Accordingly, the expression of human HMGCS2 is down-regulated in 90% of Myc-dependent colon and rectum tumors. HMGCS2 protein expression is down-regulated preferentially in moderately and poorly differentiated carcinomas. In addition, it is also down-regulated in 80% of small intestine Myc-independent tumors. Based on these findings, we propose that ketogenesis is an undesirable metabolic characteristic of the proliferating cell, which is down-regulated through c-Myc-mediated repression of the key metabolic gene HMGCS2.

  3. MSH3-deficiency initiates EMAST without oncogenic transformation of human colon epithelial cells.

    Directory of Open Access Journals (Sweden)

    Christoph Campregher

    Full Text Available BACKGROUND/AIM: Elevated microsatellite instability at selected tetranucleotide repeats (EMAST is a genetic signature in certain cases of sporadic colorectal cancer and has been linked to MSH3-deficiency. It is currently controversial whether EMAST is associated with oncogenic properties in humans, specifically as cancer development in Msh3-deficient mice is not enhanced. However, a mutator phenotype is different between species as the genetic positions of repetitive sequences are not conserved. Here we studied the molecular effects of human MSH3-deficiency. METHODS: HCT116 and HCT116+chr3 (both MSH3-deficient and primary human colon epithelial cells (HCEC, MSH3-wildtype were stably transfected with an EGFP-based reporter plasmid for the detection of frameshift mutations within an [AAAG]17 repeat. MSH3 was silenced by shRNA and changes in protein expression were analyzed by shotgun proteomics. Colony forming assay was used to determine oncogenic transformation and double strand breaks (DSBs were assessed by Comet assay. RESULTS: Despite differential MLH1 expression, both HCT116 and HCT116+chr3 cells displayed comparable high mutation rates (about 4×10(-4 at [AAAG]17 repeats. Silencing of MSH3 in HCECs leads to a remarkable increased frameshift mutations in [AAAG]17 repeats whereas [CA]13 repeats were less affected. Upon MSH3-silencing, significant changes in the expression of 202 proteins were detected. Pathway analysis revealed overexpression of proteins involved in double strand break repair (MRE11 and RAD50, apoptosis, L1 recycling, and repression of proteins involved in metabolism, tRNA aminoacylation, and gene expression. MSH3-silencing did not induce oncogenic transformation and DSBs increased 2-fold. CONCLUSIONS: MSH3-deficiency in human colon epithelial cells results in EMAST, formation of DSBs and significant changes of the proteome but lacks oncogenic transformation. Thus, MSH3-deficiency alone is unlikely to drive human colon

  4. In vitro cytotoxicity of silver nanoparticles and zinc oxide nanoparticles to human epithelial colorectal adenocarcinoma (Caco-2) cells.

    Science.gov (United States)

    Song, Yijuan; Guan, Rongfa; Lyu, Fei; Kang, Tianshu; Wu, Yihang; Chen, Xiaoqiang

    2014-11-01

    With the increasing applications of silver nanoparticles (Ag NPs) and zinc oxide nanoparticles (ZnO NPs) in foods and cosmetics, the concerns about the potential toxicities to human have been raised. The aims of this study are to observe the cytotoxicity of Ag NPs and ZnO NPs to human epithelial colorectal adenocarcinoma (Caco-2) cells in vitro, and to discover the toxicity mechanism of nanoparticles on Caco-2 cells. Caco-2 cells were exposed to 10, 25, 50, 100, 200μg/mL of Ag NPs and ZnO NPs (90nm). AO/EB double staining was used to characterize the morphology of the treated cells. The cell counting kit-8 (CCK-8) assay was used to detect the proliferation of the cells. Reactive oxygen species (ROS), superoxide dismutase (SOD) and glutathione (GSH) assay were used to explore the oxidative damage of Caco-2 cells. The results showed that Ag NPs and ZnO NPs (0-200μg/mL) had highly significant effect on the Caco-2 cells activity. ZnO NPs exerted higher cytotoxicity than Ag NPs in the same concentration range. ZnO NPs have dose-depended toxicity. The LD50 of ZnO NPs in Caco-2 cells is 0.431mg/L. Significant depletion of SOD level, variation in GSH level and release of ROS in cells treated by ZnO NPs were observed, which suggests that cytotoxicity of ZnO NPs in intestine cells might be mediated through cellular oxidative stress. While Caco-2 cells treated with Ag NPs at all experimental concentrations showed no cellular oxidative damage. Moreover, the cells' antioxidant capacity increased, and reached the highest level when the concentration of Ag NPs was 50μg/mL. Therefore, it can be concluded that Ag NPs are safer antibacterial material in food packaging materials than ZnO NPs. Copyright © 2014 Elsevier B.V. All rights reserved.

  5. In vitro cytotoxicity of silver nanoparticles and zinc oxide nanoparticles to human epithelial colorectal adenocarcinoma (Caco-2) cells

    Energy Technology Data Exchange (ETDEWEB)

    Song, Yijuan [Zhejiang Provincial Key Laboratory of Biometrology and Inspection and Quarantine, China Jiliang University, Hangzhou 310018 (China); Guan, Rongfa, E-mail: rongfaguan@163.com [Zhejiang Provincial Key Laboratory of Biometrology and Inspection and Quarantine, China Jiliang University, Hangzhou 310018 (China); Lyu, Fei [Department of Food Science and Technology, Zhejiang University of Technology, Hangzhou 310014 (China); Kang, Tianshu; Wu, Yihang [Zhejiang Provincial Key Laboratory of Biometrology and Inspection and Quarantine, China Jiliang University, Hangzhou 310018 (China); Chen, Xiaoqiang [Hubei University of Technology, Wuhan 430068 (China)

    2014-11-15

    Highlights: • The characterization of Ag NPs and ZnO NPs. • The various morphologies of Caco-2 cells stained with AO/EB. • The viability of Caco-2 cells after Ag NPs and ZnO NPs exposure. • The cytotoxicity of Ag NPs and ZnO NPs on Caco-2 cells by oxidative stress assays. - Abstract: With the increasing applications of silver nanoparticles (Ag NPs) and zinc oxide nanoparticles (ZnO NPs) in foods and cosmetics, the concerns about the potential toxicities to human have been raised. The aims of this study are to observe the cytotoxicity of Ag NPs and ZnO NPs to human epithelial colorectal adenocarcinoma (Caco-2) cells in vitro, and to discover the toxicity mechanism of nanoparticles on Caco-2 cells. Caco-2 cells were exposed to 10, 25, 50, 100, 200 μg/mL of Ag NPs and ZnO NPs (90 nm). AO/EB double staining was used to characterize the morphology of the treated cells. The cell counting kit-8 (CCK-8) assay was used to detect the proliferation of the cells. Reactive oxygen species (ROS), superoxide dismutase (SOD) and glutathione (GSH) assay were used to explore the oxidative damage of Caco-2 cells. The results showed that Ag NPs and ZnO NPs (0–200 μg/mL) had highly significant effect on the Caco-2 cells activity. ZnO NPs exerted higher cytotoxicity than Ag NPs in the same concentration range. ZnO NPs have dose-depended toxicity. The LD{sub 50} of ZnO NPs in Caco-2 cells is 0.431 mg/L. Significant depletion of SOD level, variation in GSH level and release of ROS in cells treated by ZnO NPs were observed, which suggests that cytotoxicity of ZnO NPs in intestine cells might be mediated through cellular oxidative stress. While Caco-2 cells treated with Ag NPs at all experimental concentrations showed no cellular oxidative damage. Moreover, the cells’ antioxidant capacity increased, and reached the highest level when the concentration of Ag NPs was 50 μg/mL. Therefore, it can be concluded that Ag NPs are safer antibacterial material in food packaging materials

  6. Cholinergic interactions between donepezil and prucalopride in human colon: potential to treat severe intestinal dysmotility.

    Science.gov (United States)

    Broad, J; Kung, V W S; Boundouki, G; Aziz, Q; De Maeyer, J H; Knowles, C H; Sanger, G J

    2013-11-01

    Cholinesterase inhibitors such as neostigmine are used for acute colonic pseudo-obstruction, but cardio-bronchial side-effects limit use. To minimize side-effects, lower doses could be combined with a 5-HT4 receptor agonist, which also facilitates intestinal cholinergic activity. However, safety concerns, especially in the elderly, require drugs with good selectivity of action. These include the AChE inhibitor donepezil (used for Alzheimer's disease, with reduced cardio-bronchial liability) and prucalopride, the first selective, clinically available 5-HT4 receptor agonist. This study examined their individual and potential synergistic activities in human colon. Neuronally mediated muscle contractions and relaxations of human colon were evoked by electrical field stimulation (EFS) and defined phenotypically as cholinergic, nitrergic or tachykinergic using pharmacological tools; the effects of drugs were determined as changes in 'area under the curve'. Prucalopride increased cholinergically mediated contractions (EC50 855 nM; 33% maximum increase), consistent with its ability to stimulate intestinal motility; donepezil (477%) and neostigmine (2326%) had greater efficacy. Concentrations of donepezil (30-100 nM) found in venous plasma after therapeutic doses had minimal ability to enhance cholinergic activity. However, donepezil (30 nM) together with prucalopride (3, 10 μM) markedly increased EFS-evoked contractions compared with prucalopride alone (P = 0.04). For example, the increases observed with donepezil and prucalopride 10 μM together or alone were, respectively, 105 ± 35%, 4 ± 6% and 35 ± 21% (n = 3-7, each concentration). Potential synergy between prucalopride and donepezil activity calls for exploration of this combination as a safer, more effective treatment of colonic pseudo-obstruction. © 2013 The British Pharmacological Society.

  7. Cell cycle arrest by the isoprenoids perillyl alcohol, geraniol, and farnesol is mediated by p21(Cip1) and p27(Kip1) in human pancreatic adenocarcinoma cells.

    Science.gov (United States)

    Wiseman, Dean A; Werner, Sean R; Crowell, Pamela L

    2007-03-01

    Pancreatic cancer, the fourth leading cause of cancer-associated mortality in the United States, usually presents in an advanced stage and is generally refractory to chemotherapy. As such, there is a great need for novel therapies for this disease. The naturally derived isoprenoids perillyl alcohol, farnesol, and geraniol have chemotherapeutic potential in pancreatic and other tumor types. However, their mechanisms of action in these systems are not completely defined. In this study, we investigated isoprenoid effects on the cell cycle and observed a similar antiproliferative mechanism of action among the three compounds. First, when given in combination, the isoprenoids exhibited an additive antiproliferative effect against MIA PaCa-2 human pancreatic cancer cells. Furthermore, all three compounds induced a G(0)/G(1) cell cycle arrest that coincided with an increase in the expression of the cyclin kinase inhibitor proteins p21(Cip1) and p27(Kip1) and a reduction in cyclin A, cyclin B1, and cyclin-dependent kinase (Cdk) 2 protein levels. Immunoprecipitation studies demonstrated increased association of both p21(Cip1) and p27(Kip1) with Cdk2 as well as diminished Cdk2 kinase activity after isoprenoid exposure, indicating a cell cycle-inhibitory role for p21(Cip1) and p27(Kip1) in pancreatic adenocarcinoma cells. When siRNA was used to inhibit expression of p21(Cip1) and p27(Kip1) proteins in MIA PaCa-2 cells, conditional resistance to all three isoprenoid compounds was evident. Given similar findings in this cell line and in BxPC-3 human pancreatic adenocarcinoma cells, we conclude that the chemotherapeutic isoprenoid compounds perillyl alcohol, farnesol, and geraniol invoke a p21(Cip1)- and p27(Kip1)-dependent antiproliferative mechanism in human pancreatic adenocarcinoma cells.

  8. Anticancer effect of linalool via cancer-specific hydroxyl radical generation in human colon cancer.

    Science.gov (United States)

    Iwasaki, Kenichi; Zheng, Yun-Wen; Murata, Soichiro; Ito, Hiromu; Nakayama, Ken; Kurokawa, Tomohiro; Sano, Naoki; Nowatari, Takeshi; Villareal, Myra O; Nagano, Yumiko N; Isoda, Hiroko; Matsui, Hirofumi; Ohkohchi, Nobuhiro

    2016-11-28

    To investigate the anticancer mechanisms of the monoterpenoid alcohol linalool in human colon cancer cells. The cytotoxic effect of linalool on the human colon cancer cell lines and a human fibroblast cell line was examined using the WST-8 assay. The apoptosis-inducing effect of linalool was measured using the terminal deoxynucleotidyl transferase dUTP nick-end labeling assay and flow cytometry with Annexin V. Oxidative stress was investigated by staining for diphenyl-1-pyrenylphosphine, which is a cellular lipid peroxidation marker, and electron spin resonance spectroscopy. Sixteen SCID mice xenografted with human cancer cells were randomized into 3 groups for in vivo analysis: control and low-dose and high-dose linalool groups. The control group was administered tap water orally every 3 d. The linalool treatment groups were administered 100 or 200 μg/kg linalool solution orally for the same period. All mice were sacrificed under anesthesia 21 d after tumor inoculation, and tumors and organs were collected for immunohistochemistry using an anti-4-hydroxynonenal antibody. Tumor weights were measured and compared between groups. Linalool induced apoptosis of cancer cells in vitro, following the cancer-specific induction of oxidative stress, which was measured based on spontaneous hydroxyl radical production and delayed lipid peroxidation. Mice in the high-dose linalool group exhibited a 55% reduction in mean xenograft tumor weight compared with mice in the control group (P < 0.05). In addition, tumor-specific lipid peroxidation was observed in the in vivo model. Linalool exhibited an anticancer effect via cancer-specific oxidative stress, and this agent has potential for application in colon cancer therapy.

  9. The cardiac glycoside oleandrin induces apoptosis in human colon cancer cells via the mitochondrial pathway.

    Science.gov (United States)

    Pan, Li; Zhang, Yuming; Zhao, Wanlu; Zhou, Xia; Wang, Chunxia; Deng, Fan

    2017-07-01

    Evidence indicates that the cardiac glycoside oleandrin exhibits cytotoxic activity against several different types of cancer. However, the specific mechanisms underlying oleandrin-induced anti-tumor effects remain largely unknown. The present study examined the anti-cancer effect and underlying mechanism of oleandrin on human colon cancer cells. The cytotoxicity and IC50 of five small molecule compounds (oleandrin, neriifolin, strophanthidin, gitoxigenin, and convallatoxin) in human colon cancer cell line SW480 cells and normal human colon cell line NCM460 cells were determined by cell counting and MTT assays, respectively. Apoptosis was determined by staining cells with annexin V-FITC and propidium iodide, followed by flow cytometry. Intracellular Ca2+ was determined using Fluo-3 AM,glutathione (GSH) levels were measured using a GSH detection kit,and the activity of caspase-3, -9 was measured using a peptide substrate. BAX, pro-caspase-3, -9, cytochrome C and BCL-2 expression were determined by Western blotting. Oleandrin significantly decreased cell viabilities in SW480, HCT116 and RKO cells. The IC50 for SW480 cells was 0.02 µM, whereas for NCM460 cells 0.56 µM. More interestingly, the results of flow cytometry showed that oleandrin potently induced apoptosis in SW480 and RKO cells. Oleandrin downregulated protein expression of pro-caspase-3, -9, but enhanced caspase-3, -9 activities. These effects were accompanied by upregulation of protein expression of cytochrome C and BAX, and downregulation of BCL-2 protein expression in a concentration-dependent manner. Furthermore, oleandrin increased intracellular Ca2+ concentration, but decreased GSH concentration in the cells. The present results suggest that oleandrin induces apoptosis in human colorectal cancer cells via the mitochondrial pathway. Our findings provide new insight into the mechanism of anti-cancer property of oleandrin.

  10. Peripheral KV7 channels regulate visceral sensory function in mouse and human colon.

    Science.gov (United States)

    Peiris, Madusha; Hockley, James Rf; Reed, David E; Smith, Ewan St John; Bulmer, David C; Blackshaw, L Ashley

    2017-01-01

    Background Chronic visceral pain is a defining symptom of many gastrointestinal disorders. The KV7 family (KV7.1-KV7.5) of voltage-gated potassium channels mediates the M current that regulates excitability in peripheral sensory nociceptors and central pain pathways. Here, we use a combination of immunohistochemistry, gut-nerve electrophysiological recordings in both mouse and human tissues, and single-cell qualitative real-time polymerase chain reaction of gut-projecting sensory neurons, to investigate the contribution of peripheral KV7 channels to visceral nociception. Results Immunohistochemical staining of mouse colon revealed labelling of KV7 subtypes (KV7.3 and KV7.5) with CGRP around intrinsic enteric neurons of the myenteric plexuses and within extrinsic sensory fibres along mesenteric blood vessels. Treatment with the KV7 opener retigabine almost completely abolished visceral afferent firing evoked by the algogen bradykinin, in agreement with significant co-expression of mRNA transcripts by single-cell qualitative real-time polymerase chain reaction for KCNQ subtypes and the B2 bradykinin receptor in retrogradely labelled extrinsic sensory neurons from the colon. Retigabine also attenuated responses to mechanical stimulation of the bowel following noxious distension (0-80 mmHg) in a concentration-dependent manner, whereas the KV7 blocker XE991 potentiated such responses. In human bowel tissues, KV7.3 and KV7.5 were expressed in neuronal varicosities co-labelled with synaptophysin and CGRP, and retigabine inhibited bradykinin-induced afferent activation in afferent recordings from human colon. Conclusions We show that KV7 channels contribute to the sensitivity of visceral sensory neurons to noxious chemical and mechanical stimuli in both mouse and human gut tissues. As such, peripherally restricted KV7 openers may represent a viable therapeutic modality for the treatment of gastrointestinal pathologies.

  11. [Viral infection of herpes simplex, Epstein-Barr, varicela zoster, human papilloma, cytomegalovirus, or adenovirus are not related to sinonasal adenocarcinomas].

    Science.gov (United States)

    Pérez Escuredo, Jhudit; Llorente, José Luis; Melón, Santiago; de Oña, María; García Martínez, Jorge; Alvarez Marcos, César; Hermsen, Mario

    2007-01-01

    Several types of virus have been implicated in the development of head and neck tumors. However, until now sinonasal adenocarcinomas (ACN) have not been studied. The aim of this study is to screen a series of ACN for the presence of a number of viruses known to play a role in cancer. Viral DNA sequences of herpes simplex virus, Epstein-Barr, varicela zoster, human papilloma, cytomegalovirus, and adenovirus were analysed by PCR in 37 primary ACN. Three tumors (8.1%) were positive for Epstein-Barr virus and 1 case (2.7%) for cytomegalovirus. Viral infections do not seem to play a role in the etiology of ACN.

  12. Medullary carcinoma of the colon

    DEFF Research Database (Denmark)

    Fiehn, Anne-Marie Kanstrup; Grauslund, Morten; Glenthøj, Anders

    2015-01-01

    Medullary carcinoma of the colon is a rare variant of colorectal cancer claimed to have a more favorable prognosis than conventional adenocarcinomas. The histopathologic appearance may be difficult to distinguish from poorly differentiated adenocarcinoma. The study aimed to evaluate the diagnostic...... interobserver agreement and to characterize the immunohistochemical and molecular differences between these two subgroups. Fifteen cases initially classified as medullary carcinoma and 30 cases of poorly differentiated adenocarcinomas were included. Two pathologists reviewed the slides independently without...... differences in CK20 (p = 0.005) expression and in the rate of BRAF mutations (p = 0.0035). In conclusion, medullary carcinomas of the colon are difficult to discriminate from poorly differentiated adenocarcinoma even with the help of immunohistochemical and molecular analyses. This raises the question whether...

  13. Anti Proliferative and Pro Apoptotic Effects of Flavonoid Quercetin Are Mediated by CB1 Receptor in Human Colon Cancer Cell Lines.

    Science.gov (United States)

    Refolo, Maria Grazia; D'Alessandro, Rosalba; Malerba, Natascia; Laezza, Chiara; Bifulco, Maurizio; Messa, Caterina; Caruso, Maria Gabriella; Notarnicola, Maria; Tutino, Valeria

    2015-12-01

    Quercetin, the major constituent of flavonoid and widely present in fruits and vegetables, is an attractive compound for cancer prevention due to its beneficial anti proliferative effects, showing a crucial role in the regulation of apoptosis and cell cycle signaling. In vitro studies have demonstrated that quercetin specifically influences colon cancer cell proliferation. Our experiments, using human colon adenocarcinoma cells, confirmed the anti proliferative effect of quercetin and gave intriguing new insight in to the knowledge of the mechanisms involved. We observed a significant increase in the expression of the endocannabinoids receptor (CB1-R) after quercetin treatment. CB1-R can be considered an estrogen responsive receptor and quercetin, having a structure similar to that of the estrogens, can interact with CB1-R leading to the regulation of cell growth. In order to clarify the contribution of the CB1-R to the quercetin action, we investigated some of the principal molecular pathways that are inhibited or activated by this natural compound. In particular we detected the inhibition of the major survival signals like the PI3K/Akt/mTOR and an induction of the pro apoptotic JNK/JUN pathways. Interestingly, the metabolism of β-catenin was modified by flavonoid both directly and through activated CB1-R. In all the experiments done, the quercetin action has proven to be reinforced by anandamide (Met-F-AEA), a CB1-R agonist, and partially counteracted by SR141716, a CB1-R antagonist. These findings open new perspectives for anticancer therapeutic strategies. © 2015 Wiley Periodicals, Inc.

  14. Effects of fatty acids on benzo[a]pyrene uptake and metabolism in human lung adenocarcinoma A549 cells.

    Directory of Open Access Journals (Sweden)

    Rola Barhoumi

    Full Text Available Dietary supplementation with natural chemoprotective agents is receiving considerable attention because of health benefits and lack of toxicity. In recent in vivo and in vitro experimental studies, diets rich in n-3 polyunsaturated fatty acids have been shown to provide significant anti-tumor action. In this investigation, the effects of control fatty acids (oleic acid (OA, linoleic acid (LA and n-3 PUFA, e.g., docosahexaenoic acid (DHA on the uptake and metabolism of the carcinogenic polycyclic aromatic hydrocarbon, benzo[a]pyrene (BaP was investigated in A549 cells, a human adenocarcinoma alveolar basal epithelial cell line. A549 cells activate BaP through the cytochrome P450 enzyme system to form reactive metabolites, a few of which covalently bind to DNA and proteins. Therefore, multiphoton microscopy spectral analysis combined with linear unmixing was used to identify the parent compound and BaP metabolites formed in cells, in the presence and absence of fatty acids. The relative abundance of select metabolites was associated with altered P450 activity as determined using ethoxyresorufin-O-deethylase activity in cells cultured in the presence of BSA-conjugated fatty acids. In addition, the parent compound within cellular membranes increases significantly in the presence of each of the fatty acids, with the greatest accumulation observed following DHA treatment. DHA treated cells exhibit significantly lower pyrene-like metabolites indicative of lower adducts including DNA adducts compared to control BSA, OA or LA treated cells. Further, DHA reduced the abundance of the proximate carcinogen BaP 7,8-dihydrodiol and the 3-hydroxybenzo[a]pyrene metabolites compared to other treatments. The significant changes in BaP metabolites in DHA treated cells may be mediated by the effects on the physicochemical properties of the membrane known to affect enzyme activity related to phase I and phase II metabolism. In summary, DHA is a highly bioactive chemo

  15. The in vitro photodynamic effect of laser activated gallium, indium and iron phthalocyanine chlorides on human lung adenocarcinoma cells.

    Science.gov (United States)

    Maduray, K; Odhav, B

    2013-11-05

    Metal-based phthalocyanines currently are utilized as a colorant for industrial applications but their unique properties also make them prospective photosensitizers. Photosensitizers are non-toxic drugs, which are commonly used in photodynamic therapy (PDT), for the treatment of various cancers. PDT is based on the principle that, exposure to light shortly after photosensitizer administration predominately leads to the production of reactive oxygen species for the eradication of cancerous cells and tissue. This in vitro study investigated the photodynamic effect of gallium (GaPcCl), indium (InPcCl) and iron (FePcCl) phthalocyanine chlorides on human lung adenocarcinoma cells (A549). Experimentally, 2 × 10(4)cells/ml were seeded in 24-well tissue culture plates and allowed to attach overnight, after which cells were treated with different concentrations of GaPcCl, InPcCl and FePcCl ranging from 2 μg/ml to 100 μg/ml. After 2h, cells were irradiated with constant light doses of 2.5 J/cm(2), 4.5 J/cm(2) and 8.5 J/cm(2) delivered from a diode laser (λ = 661 nm). Post-irradiated cells were incubated for 24h before cell viability was measured using the MTT Assay. At 24h after PDT, irradiation with a light dose of 2.5 J/cm(2) for each photosensitizing concentration of GaPcCl, InPcCl and FePcCl produced a significant decrease in cell viability, but when the treatment light dose was further increased to 4.5 J/cm(2) and 8.5 J/cm(2) the cell survival was less than 40%. Results also showed that photoactivated FePcCl decreased cell survival of A549 cells to 0% with photosensitizing concentrations of 40 μg/ml and treatment light dose of 2.5 J/cm(2). A 20 μg/ml photosensitizing concentration of FePcCl in combination with an increased treatment light dose of either 4.5 J/cm(2) or 8.5 J/cm(2) also resulted in 0% cell survival. This PDT study concludes that low concentrations on GaPcCl, InPcCl and FePcCl activated with low level light doses can be used for the effective in

  16. Human leukocyte antigen class I and II alleles and cervical adenocarcinoma: a pooled analysis of two epidemiologic studies

    Directory of Open Access Journals (Sweden)

    Mahboobeh eSafaeian

    2014-06-01

    Full Text Available Associations between human leukocyte antigens (HLA alleles and cervical cancer are largely representative of squamous cell carcinoma (SCC, the major histologic subtype. We evaluated the association between HLA class I (A, B, and C and class II (DRB1 and DQB1 loci and risk of cervical adenocarcinoma (ADC, a less common but aggressive histologic subtype.We pooled data from the Eastern and Western US cervical cancer studies, and evaluated the association between individual alleles and allele combinations and ADC (n=630 ADC; n=775 controls. Risk estimates were calculated for 11 a priori (based on known associations with cervical cancer regardless of histologic type and 38 non a priori common alleles, as odds ratios (OR and 95% confidence intervals (CI, adjusted for age and study. In exploratory analysis, we compared the risk associations between subgroups with HPV16 or HPV18 DNA in ADC tumor tissues in the Western US study cases and controls. Three of the a priori alleles were significantly associated with decreased risk of ADC (DRB1*13:01 (OR=0.61; 95%CI:0.41-0.93, DRB1*13:02 (OR=0.49; 95%CI:0.31-0.77, and DQB1*06:03 (OR=0.64; 95%CI:0.42-0.95; one was associated with increased risk (B*07:02(OR=1.39; 95%CI:1.07-1.79. Among alleles not previously reported, DQB1*06:04 (OR=0.46; 95%CI: 0.27-0.78 was associated with decreased risk of ADC and C*07:02 (OR=1.41; 95%CI:1.09-1.81 was associated with increased risk. We did not observe a difference by histologic subtype. ADC was most strongly associated with increased risk with B*07:02/C*07:02 alleles (OR=1.33; 95%CI:1.01-1.76 and decreased risk with DRB1*13:02/DQB1*06:04 (OR=0.41; 95%CI:0.21-0.80. Results suggest that HLA allele associations with cervical ADC are similar to those for cervical SCC. An intriguing finding was the difference in risk associated with several alleles restricted to HPV16 or HPV18 related tumors, consistent with the hypothesis that HLA recognition is HPV type specific.

  17. Patterns of Early-Life Gut Microbial Colonization during Human Immune Development: An Ecological Perspective

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    Isabelle Laforest-Lapointe

    2017-07-01

    Full Text Available Alterations in gut microbial colonization during early life have been reported in infants that later developed asthma, allergies, type 1 diabetes, as well as in inflammatory bowel disease patients, previous to disease flares. Mechanistic studies in animal models have established that microbial alterations influence disease pathogenesis via changes in immune system maturation. Strong evidence points to the presence of a window of opportunity in early life, during which changes in gut microbial colonization can result in immune dysregulation that predisposes susceptible hosts to disease. Although the ecological patterns of microbial succession in the first year of life have been partly defined in specific human cohorts, the taxonomic and functional features, and diversity thresholds that characterize these microbial alterations are, for the most part, unknown. In this review, we summarize the most important links between the temporal mosaics of gut microbial colonization and the age-dependent immune functions that rely on them. We also highlight the importance of applying ecology theory to design studies that explore the interactions between this complex ecosystem and the host immune system. Focusing research efforts on understanding the importance of temporally structured patterns of diversity, keystone groups, and inter-kingdom microbial interactions for ecosystem functions has great potential to enable the development of biologically sound interventions aimed at maintaining and/or improving immune system development and preventing disease.

  18. Antitumor Activity of Human Hydatid Cyst Fluid in a Murine Model of Colon Cancer

    Science.gov (United States)

    Russo, Sofía; Berois, Nora; Fernández, Gabriel; Freire, Teresa; Osinaga, Eduardo

    2013-01-01

    This study evaluates the antitumor immune response induced by human hydatic cyst fluid (HCF) in an animal model of colon carcinoma. We found that anti-HCF antibodies were able to identify cell surface and intracellular antigens in CT26 colon cancer cells. In prophylactic tumor challenge experiments, HCF vaccination was found to be protective against tumor formation for 40% of the mice (P = 0.01). In the therapeutic setting, HCF vaccination induced tumor regression in 40% of vaccinated mice (P = 0.05). This vaccination generated memory immune responses that protected surviving mice from tumor rechallenge, implicating the development of an adaptive immune response in this process. We performed a proteomic analysis of CT26 antigens recognized by anti-HCF antibodies to analyze the immune cross-reactivity between E. granulosus (HCF) and CT26 colon cancer cells. We identified two proteins: mortalin and creatine kinase M-type. Interestingly, CT26 mortalin displays 60% homology with E. granulosus hsp70. In conclusion, our data demonstrate the capacity of HCF vaccination to induce antitumor immunity which protects from tumor growth in an animal model. This new antitumor strategy could open new horizons in the development of highly immunogenic anticancer vaccines. PMID:24023528

  19. Antitumor Activity of Human Hydatid Cyst Fluid in a Murine Model of Colon Cancer

    Directory of Open Access Journals (Sweden)

    Edgardo Berriel

    2013-01-01

    Full Text Available This study evaluates the antitumor immune response induced by human hydatic cyst fluid (HCF in an animal model of colon carcinoma. We found that anti-HCF antibodies were able to identify cell surface and intracellular antigens in CT26 colon cancer cells. In prophylactic tumor challenge experiments, HCF vaccination was found to be protective against tumor formation for 40% of the mice (P=0.01. In the therapeutic setting, HCF vaccination induced tumor regression in 40% of vaccinated mice (P=0.05. This vaccination generated memory immune responses that protected surviving mice from tumor rechallenge, implicating the development of an adaptive immune response in this process. We performed a proteomic analysis of CT26 antigens recognized by anti-HCF antibodies to analyze the immune cross-reactivity between E. granulosus (HCF and CT26 colon cancer cells. We identified two proteins: mortalin and creatine kinase M-type. Interestingly, CT26 mortalin displays 60% homology with E. granulosus hsp70. In conclusion, our data demonstrate the capacity of HCF vaccination to induce antitumor immunity which protects from tumor growth in an animal model. This new antitumor strategy could open new horizons in the development of highly immunogenic anticancer vaccines.

  20. Human Colon Tumors Express a Dominant-Negative Form of SIGIRR That Promotes Inflammation and Colitis-Associated Colon Cancer in Mice.

    Science.gov (United States)

    Zhao, Junjie; Bulek, Katarzyna; Gulen, Muhammet F; Zepp, Jarod A; Karagkounis, Georgio; Martin, Bradley N; Zhou, Hao; Yu, Minjia; Liu, Xiuli; Huang, Emina; Fox, Paul L; Kalady, Matthew F; Markowitz, Sanford D; Li, Xiaoxia

    2015-12-01

    Single immunoglobulin and toll-interleukin 1 receptor (SIGIRR), a negative regulator of the Toll-like and interleukin-1 receptor (IL-1R) signaling pathways, controls intestinal inflammation and suppresses colon tumorigenesis in mice. However, the importance of SIGIRR in human colorectal cancer development has not been determined. We investigated the role of SIGIRR in development of human colorectal cancer. We performed RNA sequence analyses of pairs of colon tumor and nontumor tissues, each collected from 68 patients. Immunoblot and immunofluorescence analyses were used to determine levels of SIGIRR protein in primary human colonic epithelial cells, tumor tissues, and colon cancer cell lines. We expressed SIGIRR and mutant forms of the protein in Vaco cell lines. We created and analyzed mice that expressed full-length (control) or a mutant form of Sigirr (encoding SIGIRR(N86/102S), which is not glycosylated) specifically in the intestinal epithelium. Some mice were given azoxymethane (AOM) and dextran sulfate sodium to induce colitis-associated cancer. Intestinal tissues were collected and analyzed by immunohistochemical and gene expression profile analyses. RNA sequence analyses revealed increased expression of a SIGIRR mRNA isoform, SIGIRR(ΔE8), in colorectal cancer tissues compared to paired nontumor tissues. SIGIRR(ΔE8) is not modified by complex glycans and is therefore retained in the cytoplasm-it cannot localize to the cell membrane or reduce IL1R signaling. SIGIRR(ΔE8) interacts with and has a dominant-negative effect on SIGIRR, reducing its glycosylation, localization to the cell surface, and function. Most SIGIRR detected in human colon cancer tissues was cytoplasmic, whereas in nontumor tissues it was found at the cell membrane. Mice that expressed SIGIRR(N86/102S) developed more inflammation and formed larger tumors after administration of azoxymethane and dextran sulfate sodium than control mice; colon tissues from these mutant mice expressed

  1. Increased carnitine-dependent fatty acid uptake into mitochondria of human colon cancer cells induces apoptosis.

    Science.gov (United States)

    Wenzel, Uwe; Nickel, Alexander; Daniel, Hannelore

    2005-06-01

    Carnitine-dependent fatty acid import into mitochondria and beta-oxidation seem to be impaired in tumor cells. In the present study we show that a supply of palmitoylcarnitine together with L-carnitine potently induces apoptosis in HT-29 human colon cancer cells as a consequence of accelerated fatty acid oxidation. Caspase-3-like activities, measured by the cleavage rate of a fluorogenic tetrapeptide substrate and nuclear fragmentation determined after DNA labeling in fixed cells by fluorescence microscopy, served as indicators of apoptosis. Neither L-carnitine nor palmitoylcarnitine alone were able to increase caspase-3-like activities and DNA fragmentation, but when provided together, apoptosis occurred. That exogenous carnitine was indeed able to enhance fatty acid uptake into mitochondria was demonstrated by an increased influx of a fluorescent palmitic acid analog. Enhanced fatty acid availability in mitochondria led to an increased generation of O*2-, as detected by a O*2- -sensitive fluorogenic dye, indicating oxidation of delivered substrates. Benzoquinone, an O*2- scavenger, blocked O*2- generation and prevented apoptosis as initiated by the combination of palmitoylcarnitine and carnitine. The lack of effect of the ceramide synthesis inhibitor fumonisin on palmitoylcarnitine/carnitine-induced apoptosis further supports the notion that apoptotic cell death is specifically due to fatty acid oxidation. In contrast to HT-29 cells, nontransformed human colonocytes did not respond to exogenous palmitoylcarnitine/carnitine and no apoptosis was observed. In conclusion, our studies provide evidence that a limited mitochondrial fatty acid import in human colon cancer cells prevents high rates of mitochondrial O*2- production and protects colon cancer cells from apoptosis that can be overcome by an exogenous carnitine supply.

  2. E Durans Strain M4-5 Isolated From Human Colonic Flora Attenuates Intestinal Inflammation

    DEFF Research Database (Denmark)

    Avram-Hananel, L.; Stock, J.; Parlesak, Alexandr

    2010-01-01

    PURPOSE: The aim of this study was to evaluate in vitro and in vivo effects of a unique high-butyrate-producing bacterial strain from human colonic flora, Enterococcus durans, in prevention and treatment of intestinal inflammation. METHODS: A compartmentalized Caco-2/leukocyte coculture model...... was used to examine the in vitro effects of E durans and its metabolite butyrate on basal and Escherichia coli–stimulated secretion of proinflammatory immune factors (IL-8, IL-6, and TNF-α) and the anti-inflammatory cytokine IL-10. A murine model of dextran sodium sulfate-induced colitis was used...

  3. Deciphering the colon cancer genes--report of the InSiGHT-Human Variome Project Workshop, UNESCO, Paris 2010

    DEFF Research Database (Denmark)

    Kohonen-Corish, Maija R J; Macrae, Finlay; Genuardi, Maurizio

    2011-01-01

    The Human Variome Project (HVP) has established a pilot program with the International Society for Gastrointestinal Hereditary Tumours (InSiGHT) to compile all inherited variation affecting colon cancer susceptibility genes. An HVP-InSiGHT Workshop was held on May 10, 2010, prior to the HVP...... Integration and Implementation Meeting at UNESCO in Paris, to review the progress of this pilot program. A wide range of topics were covered, including issues relating to genotype-phenotype data submission to the InSiGHT Colon Cancer Gene Variant Databases (chromium.liacs.nl/LOVD2/colon_cancer...

  4. Carriers of human mitochondrial DNA macrohaplogroup M colonized India from southeastern Asia.

    Science.gov (United States)

    Marrero, Patricia; Abu-Amero, Khaled K; Larruga, Jose M; Cabrera, Vicente M

    2016-11-10

    From a mtDNA dominant perspective, the exit from Africa of modern humans to colonize Eurasia occurred once, around 60 kya, following a southern coastal route across Arabia and India to reach Australia short after. These pioneers carried with them the currently dominant Eurasian lineages M and N. Based also on mtDNA phylogenetic and phylogeographic grounds, some authors have proposed the coeval existence of a northern route across the Levant that brought mtDNA macrohaplogroup N to Australia. To contrast both hypothesis, here we reanalyzed the phylogeography and respective ages of mtDNA haplogroups belonging to macrohaplogroup M in different regions of Eurasia and Australasia. The macrohaplogroup M has a historical implantation in West Eurasia, including the Arabian Peninsula. Founder ages of M lineages in India are significantly younger than those in East Asia, Southeast Asia and Near Oceania. Moreover, there is a significant positive correlation between the age of the M haplogroups and its longitudinal geographical distribution. These results point to a colonization of the Indian subcontinent by modern humans carrying M lineages from the east instead the west side. The existence of a northern route, previously proposed for the mtDNA macrohaplogroup N, is confirmed here for the macrohaplogroup M. Both mtDNA macrolineages seem to have differentiated in South East Asia from ancestral L3 lineages. Taking this genetic evidence and those reported by other disciplines we have constructed a new and more conciliatory model to explain the history of modern humans out of Africa.

  5. Current and Potential Treatments for Reducing Campylobacter Colonization in Animal Hosts and Disease in Humans

    Science.gov (United States)

    Johnson, Tylor J.; Shank, Janette M.; Johnson, Jeremiah G.

    2017-01-01

    Campylobacter jejuni is the leading cause of bacteria-derived gastroenteritis worldwide. In the developed world, Campylobacter is usually acquired by consuming under-cooked poultry, while in the developing world it is often obtained through drinking contaminated water. Once consumed, the bacteria adhere to the intestinal epithelium or mucus layer, causing toxin-mediated inhibition of fluid reabsorption from the intestine and invasion-induced inflammation and diarrhea. Traditionally, severe or prolonged cases of campylobacteriosis have been treated with antibiotics; however, overuse of these antibiotics has led to the emergence of antibiotic-resistant strains. As the incidence of antibiotic resistance, emergence of post-infectious diseases, and economic burden associated with Campylobacter increases, it is becoming urgent that novel treatments are developed to reduce Campylobacter numbers in commercial poultry and campylobacteriosis in humans. The purpose of this review is to provide the current status of present and proposed treatments to combat Campylobacter infection in humans and colonization in animal reservoirs. These treatments include anti-Campylobacter compounds, probiotics, bacteriophage, vaccines, and anti-Campylobacter bacteriocins, all of which may be successful at reducing the incidence of campylobacteriosis in humans and/or colonization loads in poultry. In addition to reviewing treatments, we will also address several proposed targets that may be used in future development of novel anti-Campylobacter treatments. PMID:28386253

  6. Streptococcus sanguinis as an opportunistic bacteria in human oral cavity: Adherence, colonization, and invasion

    Directory of Open Access Journals (Sweden)

    Hening Tjaturina Pramesti

    2017-08-01

    Full Text Available Streptococcus sanguinis (formerly S. sanguis is a Gram-positive, facultative anaerobe,  nonmotile , normal  inhabitant of the human oral cavity, and  a member of  the viridans group of streptococci. Among the streptococcus, S. sanguinis is a  primary colonizer in the human tooth surface or it is recognize as a ‘pioneer’ by forming dental plaque. The aim of this paper is to review the role of Streptococcus sanguinis  in the adherence to and  invasion of  human tissues.  S. sanguinis  has been reported  that it is associated  with healthy  tooth  surfaces  but not with caries. S. sanguinis  tend to involved in an interspecies interactions with Streptococcus mutans, which is known as  competition/coexistence within dental biofilm.  In their colonization, this bacteria used enzyme sortase A (SrtA to cleave  LPXTG-containing proteins sequence and  anchored  the  cell wall, while virulence factors  in infective endocarditis  involved housekeeping functions such as cell wall synthesis, amino acid and nucleic acid synthesis, and the ability to survive under anaerobic conditions.

  7. [Establishment and Characterization of a Novel Chinese Human Lung Adenocarcinoma Cell Line CPA-Yang2 in Immunodeficient Mice.].

    Science.gov (United States)

    Yang, Shunfang; Su, Jianzhong; Shi, Meiping; Zhao, Lanxiang; Zhang, Peiling; Cao, Jie; Lu, Jianying; Xie, Wenhui

    2009-10-20

    The recurrence, metastasis and multidrug resistance (MDR) in lung cancer are the tough problems worldwide. This study was to establish a novel chinese lung adenocarcinoma cell line with high metastasis potential for exploring the mechanism of reccurrence, development and MDR in lung cancer. The cell came from the abdominal dropsy of a fifty-six years old female patient with lung adenocarcinoma and the tumor markers CA125, CYFRA21-1, CEA, NSE were detected to be higher secretion by radioimmunoassay in the abdominal dropsy. Tumorigenicity of immunodeficient mice was confirmed in 8th passage. The cell growth curve was mapped. Analysis of chromosome karyotype was tested. The gene expression was measured by real-time quantitative PCR. The tumorigenesis rate started at 8th passage in 3/10 immunodeficient mice via subcutaneously and the fully tumorigenicity was at 11th passage as well as later passages. Under the microscope, the cell showed oval-shap and adherence. The chromosome karyotype analysis of the cells was sub-triploid. Approximately 1*10(6) and 1.5*10(6) cancerous cells were injected into left cardiac ventricle and tail vein of immunodeficient mice respectively. The results showed multiorgan metastasis in the mice after three-four weeks, including mandible, scapula, humerus, vertebral column, femur, rib and brain, liver, adrenal gland, pulmonary in the mice after inoculation. The bone metastasis rate was 100% in the tumor bearing mice by bone scintigraphy and pathology. Quantitative real-time PCR was used to examined and compared with SPC-A-1 lung adenocarcinoma, ESM1, VEGF-C, IL-6, IL-8, AR genes were overexpressed. The novel cell was named CPA-Yang2 The characteristics of novel strain CPA-Yang2 is a highly metastasis cell line of Chinese lung adenocarcinoma. It has stable traits, highly metastasis ability and maybe is a MDR lung cancerous cell line. Of course, it's a good experimental model for lung cancer research.

  8. Time- and dose-dependent effects of curcumin on gene expression in human colon cancer cells

    NARCIS (Netherlands)

    Erk, M.J. van; Teuling, E.; Staal, Y.C.M.; Huybers, S.; Bladeren, P.J. van; Aarts, J.M.M.J.G.; Ommen, B. van

    2004-01-01

    Background. Curcumin is a spice and a coloring food compound with a promising role in colon cancer prevention. Curcumin protects against development of colon tumors in rats treated with a colon carcinogen, in colon cancer cells curcumin can inhibit cell proliferation and induce apoptosis, it is an

  9. Time- and dose-dependent effects of curcumin on gene expression in human colon cancer cells

    NARCIS (Netherlands)

    Erk, van M.J.; Teuling, E.; Staal, Y.C.M.; Huybers, S.; Bladeren, van P.J.; Aarts, J.M.M.J.G.; Ommen, van B.

    2004-01-01

    Background: Curcumin is a spice and a coloring food compound with a promising role in colon cancer prevention. Curcumin protects against development of colon tumors in rats treated with a colon carcinogen, in colon cancer cells curcumin can inhibit cell proliferation and induce apoptosis, it is an

  10. Time- and dose-dependent effects of curcumin on gene expression in human colon cancer cells

    NARCIS (Netherlands)

    Van Erk, Marjan J; Teuling, Eva; Staal, Yvonne C. M.; Huybers, Sylvie; Van Bladeren, Peter J; Aarts, Jac MMJG; Van Ommen, Ben

    2004-01-01

    BACKGROUND: Curcumin is a spice and a coloring food compound with a promising role in colon cancer prevention. Curcumin protects against development of colon tumors in rats treated with a colon carcinogen, in colon cancer cells curcumin can inhibit cell proliferation and induce apoptosis, it is an

  11. Reconstructing Holocene vegetation on the island of Gran Canaria before and after human colonization

    DEFF Research Database (Denmark)

    de Nascimento, Lea; Nogué, Sandra; Criado, Constantino

    2016-01-01

    We provide the first fossil pollen and charcoal analysis from the island of Gran Canaria (Canary Islands). The pollen record obtained from Laguna de Valleseco (870 m a.s.l.) spans the late Holocene (c. 4500–1500 cal. yr BP) and thereby captures the impact of human colonization. During the earliest......, 400 years before the earliest archaeological evidence of human presence in the island (c. 1900 cal. yr BP). Our data show an increased frequency of fires at that time, coinciding with the decline of palms and the increase of grasses, indicating that humans were present and were transforming vegetation......, thus showing that the demise of Gran Canaria’s forest began at an early point in the prehistoric occupation of the island. In the following centuries, there were no signs of forest recovery. Pollen from cultivated cereals became significant, implying the introduction of agriculture in the site, by 1800...

  12. Curcumin promotes apoptosis in A549/DDP multidrug-resistant human lung adenocarcinoma cells through an miRNA signaling pathway

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Jian, E-mail: zhangjian197011@yahoo.com [Department of Respiratory Medicine, Xijing Hospital, The Fourth Military Medical University, Xi' an 710032 (China); Zhang, Tao [Department of Thoracic Surgery, Tangdu Hospital, The Fourth Military Medical University, Xi' an 710038 (China); Ti, Xinyu; Shi, Jieran; Wu, Changgui; Ren, Xinling [Department of Respiratory Medicine, Xijing Hospital, The Fourth Military Medical University, Xi' an 710032 (China); Yin, Hong, E-mail: yinnhong@yahoo.com [The Medical Image Center, Xijing Hospital, The Fourth Military Medical University, Xi' an 710032 (China)

    2010-08-13

    Research highlights: {yields} Curcumin had anti-cancer effects on A549/DDP multidrug-resistant human lung adenocarcinoma cells {yields} Curcumin promotes apoptosis in A549/DDP cells through a miRNA signaling pathway {yields} Curcumin induces A549/DDP cell apoptosis by downregulating miR-186* {yields} miR-186* may serve as a potential gene therapy target for refractory lung cancer that is sensitive to curcumin -- Abstract: Curcumin extracted from the rhizomes of Curcuma longa L. has been shown to have inhibitory effects on cancers through its anti-proliferative and pro-apoptotic activities. Emerging evidence demonstrates that curcumin can overcome drug resistance to classical chemotherapies. Thus, the mechanisms underlying the anti-tumor activities of curcumin require further study. In our study, we first demonstrated that curcumin had anti-cancer effects on A549/DDP multidrug-resistant human lung adenocarcinoma cells. Further studies showed that curcumin altered miRNA expression; in particular, significantly downregulated the expression of miR-186* in A549/DDP. In addition, transfection of cells with a miR-186* inhibitor promoted A549/DDP apoptosis, and overexpression of miR-186* significantly inhibited curcumin-induced apoptosis in A549/DDP cells. These observations suggest that miR-186* may serve as a potential gene therapy target for refractory lung cancer that is sensitive to curcumin.

  13. Neferine augments therapeutic efficacy of cisplatin through ROS- mediated non-canonical autophagy in human lung adenocarcinoma (A549 cells).

    Science.gov (United States)

    Kalai Selvi, Sivalingam; Vinoth, Amirthalingam; Varadharajan, Thiyagarajan; Weng, Ching Feng; Vijaya Padma, Viswanadha

    2017-05-01

    Combination of dietary components with chemotherapy drugs is an emerging new strategy for cancer therapy to increase antitumor responses. Neferine, major bisbenzylisoquinoline alkaloid isolated from the seed embryo of Nelumbo nucifera (Lotus). In the present study, we investigated the efficacy of the combinatorial regimen of neferine and cisplatin compared to cisplatin high dose in human lung adenocarcinoma (A549) cells. Co-treatment with neferine enhanced cisplatin-induced autophagy in A549 cells was accompanied by Acidic vesicular accumulation (AVO), enhanced generation of reactive oxygen species (ROS) and depletion of intracellular glutathione (GSH), down regulation of PI3K/AKT/mTOR pathway, conversion of LC3B-I to LC3B-II. This enhanced autophagy developed via a non-canonical mechanism that did not require Beclin-1, PI3KCIII. In conclusion, these results suggest that neferine enhances cisplatin -induced autophagic cancer cell death through downregulation of PI3K/Akt/mTOR signaling pro-survival pathway and ROS- mediated Beclin-1 and PI3K CIII independent autophagy in human lung adenocarcinoma (A549 cells). Copyright © 2017 Elsevier Ltd. All rights reserved.

  14. Acoustic Cluster Therapy (ACT) enhances the therapeutic efficacy of paclitaxel and Abraxane® for treatment of human prostate adenocarcinoma in mice.

    Science.gov (United States)

    van Wamel, Annemieke; Sontum, Per Christian; Healey, Andrew; Kvåle, Svein; Bush, Nigel; Bamber, Jeffrey; de Lange Davies, Catharina

    2016-08-28

    Acoustic cluster therapy (ACT) is a novel approach for ultrasound mediated, targeted drug delivery. In the current study, we have investigated ACT in combination with paclitaxel and Abraxane® for treatment of a subcutaneous human prostate adenocarcinoma (PC3) in mice. In combination with paclitaxel (12mg/kg given i.p.), ACT induced a strong increase in therapeutic efficacy; 120days after study start, 42% of the animals were in stable, complete remission vs. 0% for the paclitaxel only group and the median survival was increased by 86%. In combination with Abraxane® (12mg paclitaxel/kg given i.v.), ACT induced a strong increase in the therapeutic efficacy; 60days after study start 100% of the animals were in stable, remission vs. 0% for the Abraxane® only group, 120days after study start 67% of the animals were in stable, complete remission vs. 0% for the Abraxane® only group. For the ACT+Abraxane group 100% of the animals were alive after 120days vs. 0% for the Abraxane® only group. Proof of concept for Acoustic Cluster Therapy has been demonstrated; ACT markedly increases the therapeutic efficacy of both paclitaxel and Abraxane® for treatment of human prostate adenocarcinoma in mice. Copyright © 2016 Elsevier B.V. All rights reserved.

  15. Novel snail1 target proteins in human colon cancer identified by proteomic analysis.

    Directory of Open Access Journals (Sweden)

    María Jesús Larriba

    2010-04-01

    Full Text Available The transcription factor Snail1 induces epithelial-to-mesenchymal transition (EMT, a process responsible for the acquisition of invasiveness during tumorigenesis. Several transcriptomic studies have reported Snail1-regulated genes in different cell types, many of them involved in cell adhesion. However, only a few studies have used proteomics as a tool for the characterization of proteins mediating EMT.We identified by proteomic analysis using 2D-DIGE electrophoresis combined with MALDI-TOF-TOF and ESI-linear ion trap mass spectrometry a number of proteins with variable functions whose expression is modulated by Snail1 in SW480-ADH human colon cancer cells. Validation was performed by Western blot and immunofluorescence analyses. Snail1 repressed several members of the 14-3-3 family of phosphoserine/phosphothreonine binding proteins and also the expression of the Proliferation-associated protein 2G4 (PA2G4 that was mainly localized at the nuclear Cajal bodies. In contrast, the expression of two proteins involved in RNA processing, the Cleavage and polyadenylation specificity factor subunit 6 (CPSF6 and the Splicing factor proline/glutamine-rich (SFPQ, was higher in Snail1-expressing cells than in controls. The regulation of 14-3-3epsilon, 14-3-3tau, 14-3-3zeta and PA2G4 by Snail1 was reproduced in HT29 colon cancer cells. In addition, we found an inverse correlation between 14-3-3sigma and Snail1 expression in human colorectal tumors.We have identified a set of novel Snail1 target proteins in colon cancer that expand the cellular processes affected by Snail1 and thus its relevance for cell function and phenotype.

  16. The effect of polydextrose and probiotic lactobacilli in a Clostridium difficile–infected human colonic model

    Directory of Open Access Journals (Sweden)

    Sofia D. Forssten

    2015-10-01

    Full Text Available Background: Clostridium difficile is a natural resident of the intestinal microbiota; however, it becomes harmful when the normal intestinal microbiota is disrupted, and overgrowth and toxin production occurs. The toxins can cause bloating and diarrhoea, which may cause severe disease and have the potential to cause outbreaks in hospitals and other healthcare settings. Normally, antibiotic agents are used for treatment, although for some of the patients, these treatments provide only a temporary relief with a recurrence of C. difficile–associated diarrhoea. Objective: The effects of polydextrose (PDX, Lactobacillus acidophilus NCFM, and L. paracasei Lpc-37 on the growth of C. difficile were investigated in an in vitro model of infected human large intestine. Design: The semi-continuous colonic model is composed of four connected vessels inoculated with human faecal microbes and spiked with pathogenic C. difficile (DSM 1296. PDX in two concentrations (2 and 4%, NCFM, and Lpc-37 were fed to the system during the 2-day simulation, and the growth of C. difficile and several other microbial groups were monitored using quantitative polymerase chain reaction (qPCR and 16S rDNA sequencing. Results: The microbial community structure of the simulation samples was closely grouped according to treatment, and the largest shifts in the microbial composition were seen with PDX. The microbial diversity decreased significantly with 4% PDX, and the OTU containing C. difficile was significantly (p<0.01 decreased when compared to control and lactobacilli treatments. The mean numbers of C. difficile also decreased as detected by qPCR, although the reduction did not reach statistical significance. Conclusions: The treatments influenced the colonic microbiota, and a trend for reduced numbers of C. difficile as well as alterations of several microbial groups could be detected. This suggests that PDX may be able to modulate the composition and/or function of the

  17. Microgeographic Proteomic Networks of the Human Colonic Mucosa and Their Association With Inflammatory Bowel Disease.

    Science.gov (United States)

    Li, Xiaoxiao; LeBlanc, James; Elashoff, David; McHardy, Ian; Tong, Maomeng; Roth, Bennett; Ippoliti, Andrew; Barron, Gildardo; McGovern, Dermot; McDonald, Keely; Newberry, Rodney; Graeber, Thomas; Horvath, Steve; Goodglick, Lee; Braun, Jonathan

    2016-09-01

    Interactions between mucosal cell types, environmental stressors, and intestinal microbiota contribute to pathogenesis in inflammatory bowel disease (IBD). Here, we applied metaproteomics of the mucosal-luminal interface to study the disease-related biology of the human colonic mucosa. We recruited a discovery cohort of 51 IBD and non-IBD subjects endoscopically sampled by mucosal lavage at 6 colonic regions, and a validation cohort of 38 no-IBD subjects. Metaproteome data sets were produced for each sample and analyzed for association with colonic site and disease state using a suite of bioinformatic approaches. Localization of select proteins was determined by immunoblot analysis and immunohistochemistry of human endoscopic biopsy samples. Co-occurrence analysis of the discovery cohort metaproteome showed that proteins at the mucosal surface clustered into modules with evidence of differential functional specialization (eg, iron regulation, microbial defense) and cellular origin (eg, epithelial or hemopoietic). These modules, validated in an independent cohort, were differentially associated spatially along the gastrointestinal tract, and 7 modules were associated selectively with non-IBD, ulcerative colitis, and/or Crohn's disease states. In addition, the detailed composition of certain modules was altered in disease vs healthy states. We confirmed the predicted spatial and disease-associated localization of 28 proteins representing 4 different disease-related modules by immunoblot and immunohistochemistry visualization, with evidence for their distribution as millimeter-scale microgeographic mosaic. These findings suggest that the mucosal surface is a microgeographic mosaic of functional networks reflecting the local mucosal ecology, whose compositional differences in disease and healthy samples may provide a unique readout of physiologic and pathologic mucosal states.

  18. MicroRNAs Induce Epigenetic Reprogramming and Suppress Malignant Phenotypes of Human Colon Cancer Cells.

    Directory of Open Access Journals (Sweden)

    Hisataka Ogawa

    Full Text Available Although cancer is a genetic disease, epigenetic alterations are involved in its initiation and progression. Previous studies have shown that reprogramming of colon cancer cells using Oct3/4, Sox2, Klf4, and cMyc reduces cancer malignancy. Therefore, cancer reprogramming may be a useful treatment for chemo- or radiotherapy-resistant cancer cells. It was also reported that the introduction of endogenous small-sized, non-coding ribonucleotides such as microRNA (miR 302s and miR-369-3p or -5p resulted in the induction of cellular reprogramming. miRs are smaller than the genes of transcription factors, making them possibly suitable for use in clinical strategies. Therefore, we reprogrammed colon cancer cells using miR-302s and miR-369-3p or -5p. This resulted in inhibition of cell proliferation and invasion and the stimulation of the mesenchymal-to-epithelial transition phenotype in colon cancer cells. Importantly, the introduction of the ribonucleotides resulted in epigenetic reprogramming of DNA demethylation and histone modification events. Furthermore, in vivo administration of the ribonucleotides in mice elicited the induction of cancer cell apoptosis, which involves the mitochondrial Bcl2 protein family. The present study shows that the introduction of miR-302s and miR-369s could induce cellular reprogramming and modulate malignant phenotypes of human colorectal cancer, suggesting that the appropriate delivery of functional small-sized ribonucleotides may open a new avenue for therapy against human malignant tumors.

  19. Crohn enteritis-associated small bowel adenocarcinomas exhibit gastric differentiation.

    Science.gov (United States)

    Whitcomb, Emma; Liu, Xiuli; Xiao, Shu-Yuan

    2014-02-01

    Primary small bowel adenocarcinoma is rare. Although generally similar to colonic adenocarcinoma, some small bowel adenocarcinomas exhibit unique morphologic features, particularly those arising in association with Crohn disease. In this study, 15 sporadic small bowel adenocarcinomas and 11 Crohn enteritis-associated small bowel adenocarcinomas were examined for histology and immunohistochemical profile including cytokeratins (CK) 7 and 20, intestinal markers CDX2 and MUC2, and gastric epithelial markers MUC5AC and MUC6. We found that Crohn enteritis-associated small bowel adenocarcinomas frequently resemble gastric tubular adenocarcinoma histologically. In addition, when compared to sporadic small bowel adenocarcinoma, the former expressed MUC5AC and MUC6 with much higher frequency (82% vs. 7% and 73% vs. 0%, respectively). Ten of 11 Crohn enteritis-associated small bowel adenocarcinomas (91%) were positive for at least one gastric-type marker (MUC5AC or MUC6). Expression of CK7 was also more frequent in Crohn enteritis-associated small bowel adenocarcinoma (73% versus 27%) while expression of CK20 was less frequent (64% vs. 100%). There was no difference between sporadic and Crohn enteritis-associated small bowel adenocarcinoma in expression of CDX2 (100% vs. 91%) and MUC2 (93% vs. 73%). These observations suggest that there is a difference in the morphologic and immunohistochemical characteristics of sporadic versus Crohn enteritis-associated small bowel adenocarcinoma, particularly in their expression of gastric-type mucin. The findings also suggest that gastric differentiation in Crohn enteritis-associated small bowel adenocarcinoma is related to gastric metaplasia, a common phenomenon in Crohn disease. © 2014 Elsevier Inc. All rights reserved.

  20. MCF-7 human mammary adenocarcinoma cells exhibit augmented responses to human insulin on a collagen IV surface

    DEFF Research Database (Denmark)

    Listov-Saabye, Nicolai; Jensen, Marianne Blirup; Kiehr, Benedicte

    2009-01-01

    was significantly more mitogenic than native insulin, validating the ability of the assay to identify hypermitogenic human insulin analogs. With MCF-7 cells on a collagen IV surface, the ranking of mitogens was maintained, but fold mitogenic responses and dynamic range and steepness of dose-response curves were...... increased. Also, PI3K pathway activation by insulin was enhanced on a collagen IV surface. This study provided the first determination and ranking of the mitogenic potencies of standard reference compounds in an optimized MCF-7 assay. The optimized MCF-7 assay described here is of relevance for in vitro...... toxicological testing and carcinogenicity safety assessment of new insulin compounds....

  1. Activation of prostaglandin EP receptors by lubiprostone in rat and human stomach and colon.

    Science.gov (United States)

    Bassil, A K; Borman, R A; Jarvie, E M; McArthur-Wilson, R J; Thangiah, R; Sung, E Z H; Lee, K; Sanger, G J

    2008-05-01

    Lubiprostone (Amitiza), a possible ClC-2 channel opener derived from prostaglandin E(1) and indicated for the treatment of constipation, increases chloride ion transport and fluid secretion into the intestinal lumen. As lubiprostone may also directly modulate gastrointestinal motility, we investigated its actions and the possible involvement of prostaglandin EP receptor activation on rat and human isolated gastrointestinal preparations. Rat and human isolated preparations were mounted in tissue baths for isometric recording. The effects of lubiprostone on muscle tension and on electrically stimulated, neuronal contractions were investigated in the absence and presence of EP receptor antagonists. In rat and human stomach longitudinal muscle, lubiprostone induced a contraction (pEC(50) of 7.0+/-0.0, n=4 and 6.4+/-0.2, n=3, respectively), which was inhibited by pretreatment with the EP(1) receptor antagonist, EP(1)A 300 nM (pEC(50) reduced to 6.2+/-0.2, n=6), but not by the EP(3) or EP(4) receptor antagonists (L-798106 and GW627368X, respectively, 1 microM, P>0.05). Lubiprostone also reduced electrically stimulated, neuronal contractions in rat and human colon circular muscle preparations (pIC(50) of 8.9+/-0.4, n=7 and 8.7+/-0.9, n=6, respectively), an effect mediated pre-junctionally. This effect was reduced by the EP(4) receptor antagonist (pIC(50) of 6.7+/-1.1, n=7 and 7.7+/-0.4, n=6, respectively) but not by EP(1) or EP(3) receptor antagonists. In rats and humans, lubiprostone contracts stomach longitudinal muscle and inhibits neuronally mediated contractions of colon circular muscle. Experiments are now needed to determine if this additional activity of lubiprostone contributes to its clinical efficacy and/or side-effect profile.

  2. In Vitro Degradation and Fermentation of Three Dietary Fiber Sources by Human Colonic Bacteria

    Science.gov (United States)

    Bliss, Donna Z.; Weimer, Paul J.; Jung, Hans-Joachim G.; Savik, Kay

    2013-01-01

    Although clinical benefits of dietary fiber supplementation seem to depend partially on the extent of fiber degradation and fermentation by colonic bacteria, little is known about the effect of supplemental fiber type on bacterial metabolism. In an experiment using a non-adapted human bacterial population from three normal subjects, extent of in vitro fermentation was greater for gum arabic (GA) than for psyllium (PSY), which was greater than that for carboxymethylcellulose (CMC). In a separate experiment, in vitro incubation with feces from 52 subjects with fecal incontinence, before and after random assignment to and consumption of one of three fiber (GA, PSY, or CMC) supplements or a placebo for 20-21d, indicated that prior consumption of a specific fiber source did not increase its degradation by fecal bacteria. Results suggest that the colonic microbial community enriched on a particular fiber substrate can rapidly adapt to the presentation of a new fiber substrate. Clinical implications of the findings are that intake of a fiber source by humans is not expected to result in bacterial adaptation that would require continually larger and eventually intolerable amounts of fiber to achieve therapeutic benefits. PMID:23556460

  3. Amygdalin inhibits genes related to cell cycle in SNU-C4 human colon cancer cells.

    Science.gov (United States)

    Park, Hae-Jeong; Yoon, Seo-Hyun; Han, Long-Shan; Zheng, Long-Tai; Jung, Kyung-Hee; Uhm, Yoon-Kyung; Lee, Je-Hyun; Jeong, Ji-Seon; Joo, Woo-Sang; Yim, Sung-Vin; Chung, Joo-Ho; Hong, Seon-Pyo

    2005-09-07

    The genes were divided into seven categories according to biological function; apoptosis-related, immune response-related, signal transduction-related, cell cycle-related, cell growth-related, stress response-related and transcription-related genes. We compared the gene expression profiles of SNU-C4 cells between amygdalin-treated (5 mg/mL, 24 h) and non-treated groups using cDNA microarray analysis. We selected genes downregulated in cDNA microarray and investigated mRNA levels of the genes by RT-PCR. Microarray showed that amygdalin downregulated especially genes belonging to cell cycle category: exonuclease 1 (EXO1), ATP-binding cassette, sub-family F, member 2 (ABCF2), MRE11 meiotic recombination 11 homolog A (MRE11A), topoisomerase (DNA) I (TOP1), and FK506 binding protein 12-rapamycin-associated protein 1 (FRAP1). RT-PCR analysis revealed that mRNA levels of these genes were also decreased by amygdalin treatment in SNU-C4 human colon cancer cells. These results suggest that amygdalin have an anticancer effect via downregulation of cell cycle-related genes in SNU-C4 human colon cancer cells, and might be used for therapeutic anticancer drug.

  4. Effect of essential oil of Rosa Damascena on human colon cancer cell line SW742.

    Science.gov (United States)

    Rezaie-Tavirani, Mostafa; Fayazfar, Setareh; Heydari-Keshel, Saeid; Rezaee, Mohamad Bagher; Zamanian-Azodi, Mona; Rezaei-Tavirani, Majid; Khodarahmi, Reza

    2013-01-01

    In this study, we report the effect of the essential oil of Rosa Damascena on human colon cancer cell line (SW742) and human fibroblast cells. Colon cancer is the second most common fatal malignancy. Owing to the existence of many side effects and problems related to common treatments such as surgery, chemotherapy and radiotherapy, alternative treatments are being investigated. Some herbal medicines have shown promising results against different types of cancers. Herbal medicines used have included the use naturally occurring essential oils. The essential oil of Rosa Damascena was obtained by distillation and its effect on SW742 cell-line and fibroblast cells were investigated with cell culture. The cells were cultured and different volumes of essential oil were induced to the cells. After48hincubation, cell survival was measured and using statistical analysis, the findings were evaluated and reported. This study showed that soluble part of Rosa Damascena oil increases cell proliferation in high volumes and the non-soluble component decreases cell proliferation. The effects of essential oils, such as Rosa Damascena, on cell proliferation require more thorough investigation.

  5. In vitro degradation and fermentation of three dietary fiber sources by human colonic bacteria.

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    Bliss, Donna Z; Weimer, Paul J; Jung, Hans-Joachim G; Savik, Kay

    2013-05-15

    Although clinical benefits of dietary fiber supplementation seem to depend partially on the extent of fiber degradation and fermentation by colonic bacteria, little is known about the effect of supplemental fiber type on bacterial metabolism. In an experiment using a nonadapted human bacterial population from three normal subjects, the extent of in vitro fermentation was greater for gum arabic (GA) than for psyllium (PSY), which was greater than that for carboxymethylcellulose (CMC). In a separate experiment, in vitro incubation with feces from 52 subjects with fecal incontinence, before and after random assignment to and consumption of one of three fiber (GA, PSY, or CMC) supplements or a placebo for 20-21 days, indicated that prior consumption of a specific fiber source did not increase its degradation by fecal bacteria. Results suggest that the colonic microbial community enriched on a particular fiber substrate can rapidly adapt to the presentation of a new fiber substrate. Clinical implications of the findings are that intake of a fiber source by humans is not expected to result in bacterial adaptation that would require continually larger and eventually intolerable amounts of fiber to achieve therapeutic benefits.

  6. Effect of essential oil of Rosa Damascena on human colon cancer cell line SW742

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    Rezaie-Tavirani, Mostafa; Heydari-Keshel, Saeid; Rezaee, Mohamad Bagher; Zamanian-Azodi, Mona; Rezaei-Tavirani, Majid; Khodarahmi, Reza

    2013-01-01

    Aim In this study, we report the effect of the essential oil of Rosa Damascena on human colon cancer cell line (SW742) and human fibroblast cells. Background Colon cancer is the second most common fatal malignancy. Owing to the existence of many side effects and problems related to common treatments such as surgery, chemotherapy and radiotherapy, alternative treatments are being investigated. Some herbal medicines have shown promising results against different types of cancers. Herbal medicines used have included the use naturally occurring essential oils. Patients and methods The essential oil of Rosa Damascena was obtained by distillation and its effect on SW742 cell-line and fibroblast cells were investigated with cell culture. The cells were cultured and different volumes of essential oil were induced to the cells. After48hincubation, cell survival was measured and using statistical analysis, the findings were evaluated and reported. Results This study showed that soluble part of Rosa Damascena oil increases cell proliferation in high volumes and the non-soluble component decreases cell proliferation. Conclusion The effects of essential oils, such as Rosa Damascena, on cell proliferation require more thorough investigation. PMID:24834241

  7. Primary enteric-type adenocarcinomas of the urinary bladder are histogenetically analogous to colorectal carcinomas: Immunohistochemical evaluation of 109 cases

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    Saad S. Eissa

    2010-04-01

    In conclusion, primary non-urachal enteric-type adenocarcinoma of the urinary bladder is morphologically and immunophenotypically similar – if not identical – to colonic adenocarcinoma. The frequent association of enteric carcinomas of the urinary bladder with intestinal metaplasia and/or colonic-type adenomas with dysplasia suggests possible carcinogenetic pathways similar to that observed in colorectal carcinomas.

  8. Redox-active nanoceria depolarize mitochondrial membrane of human colon cancer cells

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    Jana, Saikat Kumar; Banerjee, Priyanka; Das, Soumen; Seal, Sudipta; Chaudhury, Koel

    2014-06-01

    Nanotherapeutics is emerging as a promising option to the various limitations and side effects associated with conventional chemotherapy. The present study investigates the cytotoxic effect of redox-active cerium oxide nanoparticles (nanoceria) on human colorectal adenocarcinoma-derived cell line (HCT 15). Exposure of these cells to nanoceria for 24 h with concentration ranging between 10 and 100 μM resulted in a significant reduction of cell viability in a dose-dependent manner. Further, at a concentration of 10 µM, nanoceria exhibited time-dependent cytotoxic effect when exposed to the cells for 24, 48, and 72 h. Upon treatment of the cells with nanoceria, reactive oxygen species (ROS) and lipid peroxidation which are indicators of oxidative stress and cytotoxicity increased significantly, in a dose-dependent manner. Nanoceria was also found to depolarize the mitochondrial membrane, thereby collapsing the membrane potential and leading to initiation of apoptosis. Scanning electron microscopic study of nanoceria-treated HCT 15 cells showed morphological changes and loss of filopodia and lamellipodia, indicating arrest of metastatic spread. Summarizing, when cultured HCT 15 cells are exposed to nanoceria, a dose-dependent cytotoxic effect mediated by ROS generation is observed.

  9. Epithelial cell adhesion molecule aptamer functionalized PLGA-lecithin-curcumin-PEG nanoparticles for targeted drug delivery to human colorectal adenocarcinoma cells.

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    Li, Lei; Xiang, Dongxi; Shigdar, Sarah; Yang, Wenrong; Li, Qiong; Lin, Jia; Liu, Kexin; Duan, Wei

    2014-01-01

    To improve the efficacy of drug delivery, active targeted nanotechnology-based drug delivery systems are gaining considerable attention as they have the potential to reduce side effects, minimize toxicity, and improve efficacy of anticancer treatment. In this work CUR-NPs (curcumin-loaded lipid-polymer-lecithin hybrid nanoparticles) were synthesized and functionalized with ribonucleic acid (RNA) Aptamers (Apts) against epithelial cell adhesion molecule (EpCAM) for targeted delivery to colorectal adenocarcinoma cells. These CUR-encapsulated bioconjugates (Apt-CUR-NPs) were characterized for particle size, zeta potential, drug encapsulation, stability, and release. The in vitro specific cell binding, cellular uptake, and cytotoxicity of Apt-CUR-NPs were also studied. The Apt-CUR-NP bioconjugates exhibited increased binding to HT29 colon cancer cells and enhancement in cellular uptake when compared to CUR-NPs functionalized with a control Apt (Pcells with Apt-CUR-NP bioconjugates. The encapsulation of CUR in Apt-CUR-NPs resulted in the increased bioavailability of delivered CUR over a period of 24 hours compared to that of free CUR in vivo. These results show that the EpCAM Apt-functionalized CUR-NPs enhance the targeting and drug delivery of CUR to colorectal cancer cells. Further development of CUR-encapsulated, nanosized carriers will lead to improved targeted delivery of novel chemotherapeutic agents to colorectal cancer cells.

  10. TTF-1 Expression in Rectal Adenocarcinoma: A Case Report and Review of the Literature.

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    Belalcazar, Astrid; Krishnamurti, Uma; Shaib, Walid

    2016-01-01

    Thyroid transcription factor 1 (TTF-1) is considered a highly sensitive and specific marker for primary lung adenocarcinoma. However, in recent years retrospective studies of tumor samples have confirmed that, although rare, TTF-1 can also be expressed in colorectal adenocarcinoma. There are a few case reports of patients with TTF-1-positive colon adenocarcinoma in the medical literature but none of TTF-1-positive rectal adenocarcinoma. Here, we present a case of rectal adenocarcinoma with lung metastasis found to be TTF-1 positive on immunohistochemistry. A review and discussion of the available literature is also included.

  11. TTF-1 Expression in Rectal Adenocarcinoma: A Case Report and Review of the Literature

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    Astrid Belalcazar

    2016-11-01

    Full Text Available Thyroid transcription factor 1 (TTF-1 is considered a highly sensitive and specific marker for primary lung adenocarcinoma. However, in recent years retrospective studies of tumor samples have confirmed that, although rare, TTF-1 can also be expressed in colorectal adenocarcinoma. There are a few case reports of patients with TTF-1-positive colon adenocarcinoma in the medical literature but none of TTF-1-positive rectal adenocarcinoma. Here, we present a case of rectal adenocarcinoma with lung metastasis found to be TTF-1 positive on immunohistochemistry. A review and discussion of the available literature is also included.

  12. Establishment and Characterization of a Novel Chinese Human Lung Adenocarcinoma Cell Line CPA-Yang2 in Immunodeficient Mice

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    Shunfang YANG

    2009-10-01

    Full Text Available Background and objective The recurrence, metastasis and multidrug resistance (MDR in lung cancer are the tough problems worldwide. This study was to establish a novel chinese lung adenocarcinoma cell line with high metastasis potential for exploring the mechanism of reccurrence, development and MDR in lung cancer. Methods The cell came from the abdominal dropsy of a fifty-six years old female patient with lung adenocarcinoma and the tumor markers CA125, CYFRA21-1, CEA, NSE were detected to be higher secretion by radioimmunoassay in the abdominal dropsy. Tumorigenicity of immunodeficient mice was confirmed in 8th passage. The cell growth curve was mapped. Analysis of chromosome karyotype was tested. The gene expression was measured by real-time quantitative PCR. Results The tumorigenesis rate started at 8th passage in 3/10 immunodeficient mice via subcutaneously and the fully tumorigenicity was at 11th passage as well as later passages. Under the microscope, the cell showed oval-shap and adherence. The chromosome karyotype analysis of the cells was sub-triploid. Approximately 1×106 and 1.5×106 cancerous cells were injected into left cardiac ventricle and tail vein of immunodeficient mice respectively. The results showed multiorgan metastasis in the mice after three-four weeks, including mandible, scapula, humerus, vertebral column, femur, rib and brain, liver, adrenal gland, pulmonary in the mice after inoculation. The bone metastasis rate was 100% in the tumor bearing mice by bone scintigraphy and pathology. Quantitative real-time PCR was used to examined and compared with SPC-A-1 lung adenocarcinoma, ESM1, VEGF-C, IL-6, IL-8, AR genes were overexpressed. The novel cell was named CPA-Yang2. Conclusion The characteristics of novel strain CPA-Yang2 is a highly metastasis cell line of Chinese lung adenocarcinoma. It has stable traits, highly metastasis ability and maybe is a MDR lung cancerous cell line. Of course, it’s a good experimental

  13. Ulcerative colitis induces changes on the expression of the endocannabinoid system in the human colonic tissue.

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    Lucia Marquéz

    Full Text Available BACKGROUND: Recent studies suggest potential roles of the endocannabinoid system in gastrointestinal inflammation. Although cannabinoid CB(2 receptor expression is increased in inflammatory disorders, the presence and function of the remaining proteins of the endocannabinoid system in the colonic tissue is not well characterized. METHODOLOGY: Cannabinoid CB(1 and CB(2 receptors, the enzymes for endocannabinoid biosynthesis DAGLalpha, DAGLbeta and NAPE-PLD, and the endocannabinoid-degradating enzymes FAAH and MAGL were analysed in both acute untreated active ulcerative pancolitis and treated quiescent patients in comparison with healthy human colonic tissue by immunocytochemistry. Analyses were carried out according to clinical criteria, taking into account the severity at onset and treatment received. PRINCIPAL FINDINGS: Western blot and immunocytochemistry indicated that the endocannabinoid system is present in the colonic tissue, but it shows a differential distribution in epithelium, lamina propria, smooth muscle and enteric plexi. Quantification of epithelial immunoreactivity showed an increase of CB(2 receptor, DAGLalpha and MAGL expression, mainly in mild and moderate pancolitis patients. In contrast, NAPE-PLD expression decreased in moderate and severe pancolitis patients. During quiescent pancolitis, CB(1, CB(2 and DAGLalpha expression dropped, while NAPE-PLD expression rose, mainly in patients treated with 5-ASA or 5-ASA+corticosteroids. The number of immune cells containing MAGL and FAAH in the lamina propria increased in acute pancolitis patients, but dropped after treatment. CONCLUSIONS: Endocannabinoids signaling pathway, through CB(2 receptor, may reduce colitis-associated inflammation suggesting a potential drugable target for the treatment of inflammatory bowel diseases.

  14. [IMMUNE REGULATORY PROPERTIES OF BIFIDOBACTERIA METABOLITES DURING EUBIOSIS AND DYSBIOSIS OF THE HUMAN COLON].

    Science.gov (United States)

    Bukharin, O V; Ivanova, E V; Perunova, N B; Chainikova, I N; Nikoforov, I A; Bondarenko, T A

    2015-01-01

    Evaluate immune regulatory properties of bifidobacteria metabolites during eubiosis and dysbiosis of the human colon. Anti-cytokine activity of metabolites of bifidobacteria clinical strains and their ability to influence the production of pro- and anti-inflammatory cytokines (IL-10) by peripheral blood mononuclear cells of healthy humans was studied, taking into account microecological state of the human intestine. Determination of final concentration of cytokines in experimental and control samples was carried out by EIA. Sensitive parameters, that are suitable for evaluation of stability of human intestine microsymbiocenosis, were detected. The level of microbial seeding, concentration of TNF-α and anti-lysozyme activity turned out to be informative for bifidobacteria in eubiosis conditions. The ability of bifidoflora metabolites to influence the production of pro-inflammatory cytokines (INF-γ, TNF-α, IL-8) by human mononuclears was a significant parameter during formation of 1 - 3 degree dysbiosis. The maintenance of physiological state of intestine homeostasis is determined by immune regulatory properties of bifidobacteria metabolites, that is realized via their interaction with both cytokines (anti-cytokine activity) and production of cytokines by host immune cells (peripheral blood mononuclears).

  15. Genetics of the pig tapeworm in madagascar reveal a history of human dispersal and colonization.

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    Yanagida, Tetsuya; Carod, Jean-François; Sako, Yasuhito; Nakao, Minoru; Hoberg, Eric P; Ito, Akira

    2014-01-01

    An intricate history of human dispersal and geographic colonization has strongly affected the distribution of human pathogens. The pig tapeworm Taenia solium occurs throughout the world as the causative agent of cysticercosis, one of the most serious neglected tropical diseases. Discrete genetic lineages of T. solium in Asia and Africa/Latin America are geographically disjunct; only in Madagascar are they sympatric. Linguistic, archaeological and genetic evidence has indicated that the people in Madagascar have mixed ancestry from Island Southeast Asia and East Africa. Hence, anthropogenic introduction of the tapeworm from Southeast Asia and Africa had been postulated. This study shows that the major mitochondrial haplotype of T. solium in Madagascar is closely related to those from the Indian Subcontinent. Parasitological evidence presented here, and human genetics previously reported, support the hypothesis of an Indian influence on Malagasy culture coinciding with periods of early human migration onto the island. We also found evidence of nuclear-mitochondrial discordance in single tapeworms, indicating unexpected cross-fertilization between the two lineages of T. solium. Analyses of genetic and geographic populations of T. solium in Madagascar will shed light on apparently rapid evolution of this organism driven by recent (<2,000 yr) human migrations, following tens of thousands of years of geographic isolation.

  16. Ratio images and ultraviolet C excitation in autofluorescence imaging of neoplasms of the human colon

    Science.gov (United States)

    Renkoski, Timothy E.; Banerjee, Bhaskar; Graves, Logan R.; Rial, Nathaniel S.; Reid, Sirandon A. H.; Tsikitis, Vassiliki Liana; Nfonsam, Valentine N.; Tiwari, Piyush; Gavini, Hemanth; Utzinger, Urs

    2013-01-01

    The accepted screening technique for colon cancer is white light endoscopy. While most abnormal growths (lesions) are detected by this method, a significant number are missed during colonoscopy, potentially resulting in advanced disease. Missed lesions are often flat and inconspicuous in color. A prototype ultraviolet spectral imager measuring autofluorescence (AF) and reflectance has been developed and applied in a study of 21 fresh human colon surgical specimens. Six excitation wavelengths from 280 to 440 nm and formulaic ratio imaging were utilized to increase lesion contrast and cause neoplasms to appear bright compared to normal tissue. It was found that in the subset of lesions which were most difficult to visualize in standard color photographs [low contrast lesions, (LCLs)] a ratio image (F340/F440) of AF images excited at 340 and 440 nm produced extraordinary images and was effective in about 70% of these difficult cases. Contrast may be due to increased levels of reduced nicotinamide adenine dinucleotide, increased hemoglobin absorption, and reduced signal from submucosal collagen. A second successful ratio image (R480/R555) combined two reflectance images to produce exceptional images especially in particular LCLs where F340/F440 was ineffective. The newly discovered ratio images can potentially improve detection rate in screening with a novel AF colonoscope.

  17. The Anticancer Effects of Radachlorin-mediated Photodynamic Therapy in the Human Endometrial Adenocarcinoma Cell Line HEC-1-A.

    Science.gov (United States)

    Kim, Su-Mi; Rhee, Yun-Hee; Kim, Jong-Soo

    2017-11-01

    We investigated the effect of photodynamic therapy (PDT) using radachlorin on invasion, vascular formation and apoptosis by targeting epidermal growth factor receptor (EGFR)/vascular endothelial growth factor receptor 2 (VEGFR2) signaling pathways in the HEC-1-A endometrial adenocarcinoma cell line. To investigate the apoptotic pathway, we performed the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assay, and western blot analysis. We also evaluated the effects of PDT on tubular capillary formation in and invasion by HEC-1-A cells with a tube formation assay, invasion assay, prostaglandin E2 (PGE2) assay, and western blot analysis. PDT had anticancer effects on HEC-1-A through activation of the intrinsic pathway of apoptosis via caspase-9 and poly-(ADP-ribose) polymerase (PARP). PDT also inhibited tubular capillary formation in and invasion by HEC-1-A under VEGF pretreatment, that resulted from down-regulation of VEGFR2, EGFR, Ras homolog gene family/ member A (RhoA) and PGE2. These results are indicative of the specificity of radachlorin-mediated PDT to VEGF. The major advantage of radachlorin-mediated PDT is its selectivity for cancer tissue while maintaining adjacent normal endometrial tissue. Therefore, radachlorin-mediated PDT might offer high anticancer efficacy for endometrial adenocarcinoma and an especially useful modality for preserving fertility. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  18. Inhibitory Effects of the Survivin siRNA Transfection on Human Lung Adenocarcinoma Cells SPCA1 and SH77

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    Quanxi LIU

    2011-01-01

    Full Text Available Background and objective Survivin, a member of the inhibitor of apoptosis (IAP protein family, has been demonstrated as a potential new target for apoptosis-based therapy in cancer and lymphoma. The aim of this study is to investigate effects and mechanisms of survivin siRNA transfection on lung adenocarcinoma cell lines SPCA1 and SH77. Methods A siRNA plasmid expression vector and pSi scrambled against survivin were constructed and transfected into SPCA1 and SH77 cells with Lipofectamine 2000. The proliferations of lung adenocarcinoma SPCA1 and SH77 cells were detected by MTT. The apoptotic rate and cell cycle were detected by flow cytometer. The activity of survivin mRNA and protein expression were analyzed with RT-PCR and Western blot. Results Survivin siRNA reduced the proliferation of SPCA1 and SH77 cells. Cell cycle was inhibited in G0/G1. Expressions of survivin siRNA mRNA and protein were reduced in transfected cells compared with the control cells. Conclusion siRNA targeted against survivin can effectively suppress SPCA1 and SH77 cells proliferation and significantly induce SPCA1 and SH77 cells apoptosis.

  19. Prevention and treatment of colon cancer by peroral administration of HAMLET (human α-lactalbumin made lethal to tumour cells).

    Science.gov (United States)

    Puthia, Manoj; Storm, Petter; Nadeem, Aftab; Hsiung, Sabrina; Svanborg, Catharina

    2014-01-01

    Most colon cancers start with dysregulated Wnt/β-catenin signalling and remain a major therapeutic challenge. Examining whether HAMLET (human α-lactalbumin made lethal to tumour cells) may be used for colon cancer treatment is logical, based on the properties of the complex and its biological context. To investigate if HAMLET can be used for colon cancer treatment and prevention. Apc(Min)(/+) mice, which carry mutations relevant to hereditary and sporadic human colorectal tumours, were used as a model for human disease. HAMLET was given perorally in therapeutic and prophylactic regimens. Tumour burden and animal survival of HAMLET-treated and sham-fed mice were compared. Tissue analysis focused on Wnt/β-catenin signalling, proliferation markers and gene expression, using microarrays, immunoblotting, immunohistochemistry and ELISA. Confocal microscopy, reporter assay, immunoprecipitation, immunoblotting, ion flux assays and holographic imaging were used to determine effects on colon cancer cells. Peroral HAMLET administration reduced tumour progression and mortality in Apc(Min)(/+) mice. HAMLET accumulated specifically in tumour tissue, reduced β-catenin and related tumour markers. Gene expression analysis detected inhibition of Wnt signalling and a shift to a more differentiated phenotype. In colon cancer cells with APC mutations, HAMLET altered β-catenin integrity and localisation through an ion channel-dependent pathway, defining a new mechanism for controlling β-catenin signalling. Remarkably, supplying HAMLET to the drinking water from the time of weaning also significantly prevented tumour development. These data identify HAMLET as a new, peroral agent for colon cancer prevention and treatment, especially needed in people carrying APC mutations, where colon cancer remains a leading cause of death.

  20. Establishment of an experimental human lung adenocarcinoma cell line SPC-A-1BM with high bone metastases potency by {sup 99m}Tc-MDP bone scintigraphy

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    Yang Shunfang [Department of Nuclear Medicine, Shanghai Chest Hospital of Shanghai Jiaotong University, Shanghai 200030 (China)], E-mail: yzyg@sh163.net; Dong Qianggang [Laboratory of Mol-diagnosis, Shanghai Cancer Institute of Shanghai Jiaotong University, Shanghai 200032 (China); Yao Ming [Laboratory of Pathology, Shanghai Cancer Institute of Shanghai Jiaotong University, Shanghai 200032 (China); Shi Meiping [Department of Pathology, Shanghai Chest Hospital of Shanghai Jiaotong University, Shanghai 200030 (China); Ye Jianding [Department of Radiology, Shanghai Chest Hospital of Shanghai Jiaotong University, Shanghai 200030 (China); Zhao Langxiang [Department of Pathology, Shanghai Chest Hospital of Shanghai Jiaotong University, Shanghai 200030 (China); Su Jianzhong; Gu Weiyong [Shanghai Thoracic Tumor Institute, Shanghai Chest Hospital of Shanghai Jiaotong University, Shanghai 200030 (China); Xie Wenhui [Department of Nuclear Medicine, Shanghai Chest Hospital of Shanghai Jiaotong University, Shanghai 200030 (China); Wang Kankan; Du Yanzhi [State Key Laboratory of Medical Genomics, Ruijin Hospital of Shanghai Jiaotong University, Shanghai 200025 (China); Li Yao [State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Science, Fudan University, Shanghai 200433 (China); Huang Yan [State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Science, Fudan University, Shanghai 200433 (China)], E-mail: huangyan@fudan.edu.cn

    2009-04-15

    Background: Bone metastasis is one of the most common clinical phenomena of late stage lung cancer. A major impediment to understanding the pathogenesis of bone metastasis has been the lack of an appropriate animal and cell model. This study aims to establish human lung adenocarcinoma cell line with highly bone metastases potency with {sup 99m}Tc-MDP bone scintigraphy. Methods: The human lung adenocarcinoma cancer cells SPC-A-1 were injected into the left cardiac ventricle of NIH-Beige-Nude-XID (NIH-BNX) immunodeficient mice. The metastatic lesions of tumor-bearing mice were imaged with {sup 99m}Tc-MDP bone scintigraphy on a Siemens multi-single photon emission computed tomography. Pinhole images were acquired on a GZ-B conventional gamma camera with a self-designed pinhole collimator. The mice with bone metastasis were sacrificed under deep anesthesia, and the lesions were resected. Bone metastatic cancer cells in the resected lesions were subjected for culture and then reinoculated into the NIH-BNX mice through left cardiac ventricle. The process was repeated for eight cycles to obtain a novel cell subline SPC-A-1BM. Real-time polymerase chain reaction (PCR) was used to compare the gene expression differences in the parental and SPC-A-1BM cells. Results: The bone metastasis sites were successfully revealed by bone scintigraphy. The established bone metastasis cell line SPC-A-1BM had a high potential to metastasize in bone, including mandible, humerus, thoracic vertebra, lumbar, femur, patella, ilium and cartilage rib. The expression level of vascular endothelial growth factor gene family, Bcl-2 and cell adhesion-related genes ECM1, ESM1, AF1Q, SERPINE2 and FN1 were examined. Gene expression difference was found between parental and bone-seeking metastasis cell SPC-A-1BM, which indicates SPC-A-1BM has metastatic capacity vs. its parental cells. Conclusion: SPC-A-1BM is a bone-seeking metastasis human lung adenocarcinoma cell line. Bone scintigraphy may be used as

  1. Nasal colonization of humans with methicillin-resistant Staphylococcus aureus (MRSA CC398 with and without exposure to pigs.

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    Christiane Cuny

    Full Text Available BACKGROUND: Studies in several European countries and in North America revealed a frequent nasal colonization of livestock with MRSA CC398 and also in humans with direct professional exposure to colonized animals. The study presented here addresses the question of further transmission to non exposed humans. METHODS: After selecting 47 farms with colonized pigs in different regions of Germany we sampled the nares of 113 humans working daily with pigs and of their 116 non exposed family members. The same was performed in 18 veterinarians attending pig farms and in 44 of their non exposed family members. For investigating transmission beyond families we samples the nares of 462 pupils attending a secondary school in a high density pig farming area. MRSA were detected by direct culture on selective agar. The isolates were typed by means of spa-sequence typing and classification of SCCmec elements. For attribution of spa sequence types to clonal lineages as defined by multi locus sequence typing we used the BURP algorithm. Antibiotic susceptibility testing was performed by microbroth dilution assay. RESULTS: At the farms investigated 86% of humans exposed and only 4.3% of their family members were found to carry MRSA exhibiting spa-types corresponding to clonal complex CC398. Nasal colonization was also found in 45% of veterinarians caring for pig farms and in 9% of their non exposed family members. Multivariate analysis revealed that antibiotic usage prior to sampling beard no risk with respect to colonization. From 462 pupils only 3 were found colonized, all 3 were living on pig farms. CONCLUSION: These results indicate that so far the dissemination of MRSA CC398 to non exposed humans is infrequent and probably does not reach beyond familial communities.

  2. [P53 protein in adenocarcinoma of the large intestine].

    Science.gov (United States)

    Paluszkiewicz, P; Pawłowska-Wakowicz, B; Cybulski, M; Berbeć, H

    1997-01-01

    P53 gen mutations play significant role in neoplastic transformation of colorectal mucosa. We investigated p53 immunostaining in 80 cases of spontaneous human colorectal adenocarcinomas (with monoclonal DO7 antibody and LSAB+ kit). We found positive, nuclear p53 immunostaining in 64% of nonmucinous adenocarcinoma tissues and in 19% of mucinous adenocarcinomas tissues. P53 protein deposits were most often found in colorectal adenocarcinomas localised in rectum (66.67%) and in advanced (Dukes C, D) colorectal adenocarcinomas (59.38%) as well. There was no statistical significance between the p53 positive immunostaining and the histological differentiation of the colorectal adenocarcinomas. The overall survival of patients with tumours positive for p53 protein was significantly shorter than that of patients with colorectal cancers negative for p53 protein. We conclude that p53 immunohistochemical analysis may be treated as a supplementary prognostic marker for patients with colorectal adenocarcinoma, especially it may be useful for adjuvant therapy selection.

  3. Antioxidative Effects of Phenolic Compounds of Mushroom Mycelia in Simulated Regions of the Human Colon, In Vitro Study

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    Vamanu Emanuel

    2018-03-01

    Full Text Available Many compounds in mushrooms are biologically active; however, the in vivo actions of their metabolites are poorly understood. An in vitro system, GIS1, was used to simulate the fermentation action of microbiota in each colon region. We used MycoPo, a natural product obtained from the lyophilized mycelia of different Pleurotus ostreatus species to determine the biological effects in human-colon regions. Controls (Lentinula edodes mycelia; dried basidia of Agaricus brunnescens were chosen to confirm the biological activity of P. ostreatus mycelia in vitro. We measured total antioxidant capacity and ferric ion-reducing antioxidant power (FRAP in simulated colon regions to identify antioxidant compounds, and undertook in vitro gastrointestinal simulation and microbiological analyses. The highest FRAP was found for the ascending colon, and the antioxidant effect was higher when MycoPo was administered. A. brunnescens consumption resulted in low total antioxidant capacity. Polyphenol content was correlated with the antioxidant status and microbial composition of microbiota. Total polyphenolic content was higher after A. brunnescens consumption, and four types of polyphenols were identified by high-performance liquid chromatography. Major phenolic acids were gentisic acid, homogentisic acid, and small amounts of caffeic acid. The Enterobacteriaceae species populations varied greatly across the three parts of the colon. We noted a significant (p0.85. These data suggest a direct relationship between favorable bacterial strains and availability of bioactive compounds, with specificity for each colon region.

  4. Characterisation of early mucosal and neuronal lesions following Shigella flexneri infection in human colon.

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    Emmanuel Coron

    Full Text Available BACKGROUND: Shigella, an enteroinvasive bacteria induces a major inflammatory response responsible for acute rectocolitis in humans. However, early effect of Shigella flexneri (S. flexneri infection upon the human mucosa and its microenvironement, in particular the enteric nervous system, remains currently unknown. Therefore, in this study, we sought to characterize ex vivo the early events of shigellosis in a model of human colonic explants. In particular, we aimed at identifying factors produced by S. flexneri and responsible for the lesions of the barrier. We also aimed at determining the putative lesions of the enteric nervous system induced by S. flexneri. METHODOLOGY/PRINCIPAL FINDINGS: We first showed that, following 3 h of infection, the invasive but not the non-invasive strain of S. flexneri induced significant desquamation of the intestinal epithelial barrier and a reduction of epithelial height. These changes were significantly reduced following infection with SepA deficient S. flexneri strains. Secondly, S. flexneri induced rapid neuronal morphological alterations suggestive of cell death in enteric submucosal neurones. These alterations were associated with a significant increase in the proportion of vasoactive intestinal peptide (VIP immunoreactive (IR neurons but not in total VIP levels. The NMDA receptor antagonist MK-801 blocked neuronal morphological changes induced by S. flexneri, but not the increase in the proportion of VIP-IR. CONCLUSIONS/SIGNIFICANCE: This human explant model can be used to gain better insight into the early pathogenic events following S. flexneri infection and the mechanisms involved.

  5. New carbon dates link climatic change with human colonization and Pleistocene extinctions.

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    Guthrie, R Dale

    2006-05-11

    Drastic ecological restructuring, species redistribution and extinctions mark the Pleistocene-Holocene transition, but an insufficiency of numbers of well-dated large mammal fossils from this transition have impeded progress in understanding the various causative links. Here I add many new radiocarbon dates to those already published on late Pleistocene fossils from Alaska and the Yukon Territory (AK-YT) and show previously unrecognized patterns. Species that survived the Pleistocene, for example, bison (Bison priscus, which evolved into Bison bison), wapiti (Cervus canadensis) and, to a smaller degree, moose (Alces alces), began to increase in numbers and continued to do so before and during human colonization and before the regional extinction of horse (Equus ferus) and mammoth (Mammuthus primigenius). These patterns allow us to reject, at least in AK-YT, some hypotheses of late Pleistocene extinction: 'Blitzkrieg' version of simultaneous human overkill, 'keystone' removal, and 'palaeo-disease'. Hypotheses of a subtler human impact and/or ecological replacement or displacement are more consistent with the data. The new patterns of dates indicate a radical ecological sorting during a uniquely forage-rich transitional period, affecting all large mammals, including humans.

  6. Ex vivo photometric and polarimetric multilayer characterization of human healthy colon by multispectral Mueller imaging

    Science.gov (United States)

    Pierangelo, Angelo; Manhas, Sandeep; Benali, Abdelali; Fallet, Clément; Antonelli, Maria-Rosaria; Novikova, Tatiana; Gayet, Brice; Validire, Pierre; De Martino, Antonello

    2012-06-01

    Healthy human colon samples were analyzed ex vivo with a multispectral imaging Mueller polarimeter operating from 500 to 700 nm in a backscattering configuration with diffuse light illumination impinging on the innermost tissue layer, the mucosa. The intensity and polarimetric responses were taken on whole tissues first and after progressive exfoliation of the outer layers afterwards. Moreover, these measurements were carried out with two different substrates (one bright and the other dark) successively placed beneath each sample, allowing a reasonably accurate evaluation of the contributions to the overall backscattered light by the various layers. For the shorter investigated wavelengths (500 to 550 nm) the major contribution comes from mucosa and submucosa, while for the longer wavelengths (650 to 700 nm) muscular tissue and fat also contribute significantly. The depolarization has also been studied and is found to be stronger in the red part of the spectrum, mainly due to the highly depolarizing power of the muscular and fat layers.

  7. Effects of menthol on circular smooth muscle of human colon: analysis of the mechanism of action.

    Science.gov (United States)

    Amato, Antonella; Liotta, Rosa; Mulè, Flavia

    2014-10-05

    Menthol is the major constituent of peppermint oil, an herbal preparation commonly used to treat nausea, spasms during colonoscopy and irritable bowel disease. The mechanism responsible for its spasmolytic action remains unclear. The aims of this study were to investigate the effects induced by menthol on the human distal colon mechanical activity in vitro and to analyze the mechanism of action. The spontaneous or evoked-contractions of the circular smooth muscle were recorded using vertical organ bath. Menthol (0.1 mM-30 mM) reduced, in a concentration-dependent manner, the amplitude of the spontaneous contractions without affecting the frequency and the resting basal tone. The inhibitory effect was not affected by 5-benzyloxytryptamine (1 μM), a transient receptor potential-melastatin8 channel antagonist, or tetrodotoxin (1 μM), a neural blocker, or 1H-[1,2,4] oxadiazolo [4,3-a]quinoxalin-1-one (10 µM), inhibitor of nitric oxide (NO)-sensitive soluble guanylyl cyclase, or tetraethylammonium (10 mM), a blocker of potassium (K+)-channels. On the contrary, nifedipine (3 nM), a voltage-activated L-type Ca2+ channel blocker, significantly reduced the inhibitory menthol actions. Menthol also reduced in a concentration-dependent manner the contractile responses caused by exogenous application of Ca2+ (75-375 μM) in a Ca2+-free solution, or induced by potassium chloride (KCl; 40 mM). Moreover menthol (1-3 mM) strongly reduced the electrical field stimulation (EFS)-evoked atropine-sensitive contractions and the carbachol-contractile responses. The present results suggest that menthol induces spasmolytic effects in human colon circular muscle inhibiting directly the gastrointestinal smooth muscle contractility, through the block of Ca2+ influx through sarcolemma L-type Ca2+ channels. Copyright © 2014 Elsevier B.V. All rights reserved.

  8. L-Ascorbic acid can abrogate SVCT-2-dependent cetuximab resistance mediated by mutant KRAS in human colon cancer cells.

    Science.gov (United States)

    Jung, Soo-A; Lee, Dae-Hee; Moon, Jai-Hee; Hong, Seung-Woo; Shin, Jae-Sik; Hwang, Ih Yeon; Shin, Yu Jin; Kim, Jeong Hee; Gong, Eun-Yeung; Kim, Seung-Mi; Lee, Eun Young; Lee, Seul; Kim, Jeong Eun; Kim, Kyu-Pyo; Hong, Yong Sang; Lee, Jung Shin; Jin, Dong-Hoon; Kim, TaeWon; Lee, Wang Jae

    2016-06-01

    Colon cancer patients with mutant KRAS are resistant to cetuximab, an antibody directed against the epidermal growth factor receptor, which is an effective clinical therapy for patients with wild-type KRAS. Numerous combinatorial therapies have been tested to overcome the resistance to cetuximab. However, no combinations have been found that can be used as effective therapeutic strategies. In this study, we demonstrate that L-ascorbic acid partners with cetuximab to induce killing effects, which are influenced by sodium-dependent vitamin C transporter 2 (SVCT-2) in human colon cancer cells with a mutant KRAS. L-Ascorbic acid treatment of human colon cancer cells that express a mutant KRAS differentially and synergistically induced cell death with cetuximab in a SVCT-2-dependent manner. The ectopic expression of SVCT-2 induced sensitivity to L-ascorbic acid treatment in human colon cancer cells that do not express SVCT-2, whereas the knockdown of endogenous SVCT-2 induced resistance to L-ascorbic acid treatment in SVCT-2-positive cells. Moreover, tumor regression via the administration of L-ascorbic acid and cetuximab in mice bearing tumor cell xenografts corresponded to SVCT-2 protein levels. Interestingly, cell death induced by the combination of L-ascorbic acid and cetuximab resulted in both apoptotic and necrotic cell death. These cell death mechanisms were related to a disruption of the ERK pathway and were represented by the impaired activation of RAFs and the activation of the ASK-1-p38 pathway. Taken together, these results suggest that resistance to cetuximab in human colon cancer patients with a mutant KRAS can be bypassed by L-ascorbic acid in an SVCT-2-dependent manner. Furthermore, SVCT-2 in mutant KRAS colon cancer may act as a potent marker for potentiating L-ascorbic acid co-treatment with cetuximab. Copyright © 2016 Elsevier Inc. All rights reserved.

  9. Augmentation of the cytotoxic effects of zinc oxide nanoparticles by MTCP conjugation: Non-canonical apoptosis and autophagy induction in human adenocarcinoma breast cancer cell lines.

    Science.gov (United States)

    Mozdoori, Najmeh; Safarian, Shahrokh; Sheibani, Nader

    2017-09-01

    Zinc oxide nanoparticles are very toxic, but their agglomeration reduces their lethal cytotoxic effects. Here we tested the hypothesis that conjugation of ZnO nanoparticles via Meso-Tetra (4-Carboxyphenyl) Porphyrin (MTCP) could provide electrostatic or steric stabilization of ZnO nanoparticles and increase their cytotoxic effects. The cytotoxicity and cell death induction were assessed using two human breast adenocarcinoma cell lines (MCF-7 and MDA-MB-468). The MTT results indicated that the toxicity of ZnO nanoparticles was significantly increased upon MTCP conjugation. Annexin/PI and real time RT-PCR results demonstrated that the ZnO-MTCP nanoparticles induced cell death via different non-canonical pathways that are under ca2+ control. Calcium signaling could regulate lysosomal dependent apoptosis and death autophagy, and killing of the two selected types of breast cancer cells. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. Akt/mTOR mediated induction of bystander effect signaling in a nucleus independent manner in irradiated human lung adenocarcinoma epithelial cells.

    Science.gov (United States)

    Li, Lu; Wang, Lu; Prise, Kevin M; Yu, K N; Chen, Guodong; Chen, Lianyun; Mei, Yide; Han, Wei

    2017-03-14

    Cytoplasm is an important target for the radiation-induced bystander effect (RIBE). In the present work, the critical role of protein kinase B (Akt)/mammalian target of rapamycin (mTOR) pathway in the generation of RIBE signaling after X-ray irradiation and the rapid phosphorylation of Akt and mTOR was observed in the cytoplasm of irradiated human lung adenocarcinoma epithelial (A549) cells. Targeting A549 cytoplasts with individual protons from a microbeam showed that RIBE signal(s) mediated by the Akt/mTOR pathway were generated even in the absence of a cell nucleus. These results provide a new insight into the mechanisms driving the cytoplasmic response to irradiation and their impact on the production of RIBE signal(s).

  11. Human colon cancers as a major problem in poland and in the world – medical and environmental issues

    Directory of Open Access Journals (Sweden)

    Sylwia Katarzyna Król

    2011-12-01

    Full Text Available Many epidemiological data have shown an increasing incidence and mortality of colon cancer cases in the past several years, not only in Poland but all over the world as well. Each year, approximately a million new cases of colon cancer are diagnosed and that is the cause of death of almost half a million patients in the world. The aim of this article is to present the epidemiology and the current state of scientific knowledge concerning etiology and pathogenesis of neoplastic diseases in human large intestine. Furthermore, this short review describes the essential risk factors and suggests the simple and effective ways of colon cancer prevention.Colorectal cancer is one of the most frequently diagnosed cancers in EU countries. Scientific studies have proved that genetic and hereditary factors have a strong influence on carcinogenesis in human colon. Moreover, environmental factors, such as dietary contribute to the development of colon neoplasm. The most useful tool to reduce high morbidity and mortality is a prevention. Screening tests in nonsymptomatic people from high-risk groups or populations enable diagnosis in the early stage of colorectal cancer. Many publications have reported that modification of lifestyle and daily diet also play a significant role in prevention.

  12. Flavonoids and Tannins from Smilax china L. Rhizome Induce Apoptosis Via Mitochondrial Pathway and MDM2-p53 Signaling in Human Lung Adenocarcinoma Cells.

    Science.gov (United States)

    Fu, San; Yang, Yanfang; Liu, Dan; Luo, Yan; Ye, Xiaochuan; Liu, Yanwen; Chen, Xin; Wang, Song; Wu, Hezhen; Wang, Yuhang; Hu, Qiwei; You, Pengtao

    2017-01-01

    In vitro evidence indicates that Smilax china L. rhizome (SCR) can inhibit cell proliferation. Therefore, in the present study, we analyzed the effects in vitro of SCR extracts on human lung adenocarcinoma A549 cells. Our results showed that A549 cell growth was inhibited in a dose- and time-dependent manner after treatment with SCR extracts. Total flavonoids and total tannins from SCR induced A549 apoptosis in a dose-dependent manner, as shown by our flow cytometry analysis, which was consistent with the alterations in nuclear morphology we observed. In addition, the total apoptotic rate induced by total tannins was higher than the rate induced by total flavonoids at the same dose. Cleaved-caspase-3 protein levels in A549 cells after treatment with total flavonoids or total tannins were increased in a dose-dependent manner, followed by the activation of caspase-8 and caspase-9, finally triggering to PARP cleavage. Furthermore, total flavonoids and total tannins increased the expression of Bax, decreased the expression of Bcl-2, and promoted cytochrome [Formula: see text] release. Moreover, MDM2 and p-MDM2 proteins were decreased, while p53 and p-p53 proteins were increased, both in a dose-dependent manner, after A549 treatment with total flavonoids and total tannins. Finally, cleaved-caspase-3 protein levels in the total flavonoids or total tannins-treated H1299 (p53 null) and p53-knockdown A549 cells were increased. Our results indicated that total flavonoids and total tannins from SCR exerted a remarkable effect in reducing A549 growth through their action on mitochondrial pathway and disruption of MDM2-p53 balance. Hence, our findings demonstrated a potential application of total flavonoids and total tannins from SCR in the treatment of human lung adenocarcinoma.

  13. The Effect of Various Inulins and Clostridium difficile on the Metabolic Activity of the Human Colonic Microbiota in vitro

    NARCIS (Netherlands)

    Nuenen, M.H.M.C. van; Meyer, P.D.; Venema, K.

    2003-01-01

    The influence of inulins with different average degree of polymerization (ranging from 3 to 25) on the metabolic activity of the human colonic microbiota with or without the addition of Clostridium difficile was investigated in vitro. The in vitro system used was a dynamic, computer-controlled model

  14. Deciphering the Colon Cancer Genes-Report of the InSiGHT-Human Variome Project Workshop, UNESCO, Paris 2010

    NARCIS (Netherlands)

    Kohonen-Corish, Maija R. J.; Macrae, Finlay; Genuardi, Maurizio; Aretz, Stefan; Bapat, Bharati; Bernstein, Inge T.; Burn, John; Cotton, Richard G. H.; den Dunnen, Johan T.; Frebourg, Thierry; Greenblatt, Marc S.; Hofstra, Robert; Holinski-Feder, Elke; Lappalainen, Ilkka; Lindblom, Annika; Maglott, Donna; Moller, Pal; Morreau, Hans; Moeslein, Gabriela; Sijmons, Rolf; Spurdle, Amanda B.; Tavtigian, Sean; Tops, Carli M. J.; Weber, Thomas K.; de Wind, Niels; Woods, Michael O.

    The Human Variome Project (HVP) has established a pilot program with the International Society for Gastrointestinal Hereditary Tumours (InSiGHT) to compile all inherited variation affecting colon cancer susceptibility genes. An HVP-InSiGHT Workshop was held on May 10, 2010, prior to the HVP

  15. Osthole inhibits the invasive ability of human lung adenocarcinoma cells via suppression of NF-κB-mediated matrix metalloproteinase-9 expression

    Energy Technology Data Exchange (ETDEWEB)

    Kao, Shang-Jyh [Department of Chest Medicine, Shin-Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan (China); School of Respiratory Therapy, Taipei Medical University, Taipei Taiwan (China); Su, Jen-Liang [Graduate Institute of Cancer Biology, College of Medicine, China Medical University, Taichung, Taiwan (China); Center for Molecular Medicine, China Medical University Hospital, Taichung, Taiwan (China); Department of Biotechnology, Asia University, Taichung, Taiwan (China); Chen, Chi-Kuan [Graduate Institute of Toxicology, College of Medicine, National Taiwan University, Taipei, Taiwan (China); Yu, Ming-Chih; Bai, Kuan-Jen; Chang, Jer-Hua [Division of Pulmonary Medicine, Department of Internal Medicine, Taipei Medical University-Wan Fang Hospital, Taipei, Taiwan (China); Bien, Mauo-Ying [School of Respiratory Therapy, Taipei Medical University, Taipei Taiwan (China); Division of Pulmonary Medicine, Department of Internal Medicine, Taipei Medical University-Wan Fang Hospital, Taipei, Taiwan (China); Yang, Shun-Fa [Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan (China); Department of Medical Research, Chung Shan Medical University Hospital, Taichung, Taiwan (China); Chien, Ming-Hsien, E-mail: mhchien1976@gmail.com [Graduate Institute of Clinical Medicine, Taipei Medical University, Taipei, Taiwan (China)

    2012-05-15

    The induction of matrix metalloproteinase (MMP)-9 is particularly important for the invasiveness of various cancer cells. Osthole, a natural coumarin derivative extracted from traditional Chinese medicines, is known to inhibit the proliferation of a variety of tumor cells, but the effect of osthole on the invasiveness of tumor cells is largely unknown. This study determines whether and by what mechanism osthole inhibits invasion in CL1-5 human lung adenocarcinoma cells. Herein, we found that osthole effectively inhibited the migratory and invasive abilities of CL1-5 cells. A zymographic assay showed that osthole inhibited the proteolytic activity of MMP-9 in CL1-5 cells. Inhibition of migration, invasion, and MMP2 and/or MMP-9 proteolytic activities was also observed in other lung adenocarcinoma cell lines (H1299 and A549). We further found that osthole inhibited MMP-9 expression at the messenger RNA and protein levels. Moreover, a chromatin immunoprecipitation assay showed that osthole inhibited the transcriptional activity of MMP-9 by suppressing the DNA binding activity of nuclear factor (NF)-κB in the MMP-9 promoter. Using reporter assays with point-mutated promoter constructs further confirmed that the inhibitory effect of osthole requires an NF-κB binding site on the MMP-9 promoter. Western blot and immunofluorescence assays demonstrated that osthole inhibited NF-κB activity by inhibiting IκB-α degradation and NF-κB p65 nuclear translocation. In conclusion, we demonstrated that osthole inhibits NF-κB-mediated MMP-9 expression, resulting in suppression of lung cancer cell invasion and migration, and osthole might be a potential agent for preventing the invasion and metastasis of lung cancer. -- Highlights: ► Osthole treatment inhibits lung adenocarcinoma cells migration and invasion. ► Osthole reduces the expression and proteolytic activity of MMP-9. ► Osthole inhibits MMP-9 transcription via suppression of NF-κB binding activity. ► Osthole

  16. Skeletal Muscle Metastasis from a Cecal Mucinous Adenocarcinoma: A Case Report

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Dong Hyun; Lee, Young Hwan; Jung, Kyung Jae [Catholic University, Daegu (Korea, Republic of); Park, Young Chan; Kim, Ho Kyun; Cho, Seung Hyun [Seoul National University College of Medicine, Seoul (Korea, Republic of)

    2008-11-15

    Skeletal muscle metastasis is a relatively rare finding in the setting of mucinous adenocarcinoma of the colon, and it typically exhibits nonspecific imaging findings. We report a case of a skeletal muscle metastasis originating from mucinous adenocarcinoma of the cecum. The skeletal lesion closely resembled intramuscular myxoma with regard to imaging findings, due to abundant mucin and internal calcification.

  17. Shiga Toxin Glycosphingolipid Receptors in Human Caco-2 and HCT-8 Colon Epithelial Cell Lines.

    Science.gov (United States)

    Kouzel, Ivan U; Pohlentz, Gottfried; Schmitz, Julia S; Steil, Daniel; Humpf, Hans-Ulrich; Karch, Helge; Müthing, Johannes

    2017-10-25

    Shiga toxins (Stxs) released by enterohemorrhagic Escherichia coli (EHEC) into the human colon are the causative agents for fatal outcome of EHEC infections. Colon epithelial Caco-2 and HCT-8 cells are widely used for investigating Stx-mediated intestinal cytotoxicity. Only limited data are available regarding precise structures of their Stx receptor glycosphingolipids (GSLs) globotriaosylceramide (Gb3Cer) and globotetraosylceramide (Gb4Cer), and lipid raft association. In this study we identified Gb3Cer and Gb4Cer lipoforms of serum-free cultivated Caco-2 and HCT-8 cells, chiefly harboring ceramide moieties composed of sphingosine (d18:1) and C16:0, C22:0 or C24:0/C24:1 fatty acid. The most significant difference between the two cell lines was the prevalence of Gb3Cer with C16 fatty acid in HCT-8 and Gb4Cer with C22-C24 fatty acids in Caco-2 cells. Lipid compositional analysis of detergent-resistant membranes (DRMs), which were used as lipid raft-equivalents, indicated slightly higher relative content of Stx receptor Gb3Cer in DRMs of HCT-8 cells when compared to Caco-2 cells. Cytotoxicity assays revealed substantial sensitivity towards Stx2a for both cell lines, evidencing little higher susceptibility of Caco-2 cells versus HCT-8 cells. Collectively, Caco-2 and HCT-8 cells express a plethora of different receptor lipoforms and are susceptible towards Stx2a exhibiting somewhat lower sensitivity when compared to Vero cells.

  18. Transcriptomic responses of cancerous and noncancerous human colon cells to sulforaphane and selenium.

    Science.gov (United States)

    Constantinescu, Simona; Hecht, Katrin; Sobotzki, Nadine; Erzinger, Melanie M; Bovet, Cédric; Shay, Jerry W; Wollscheid, Bernd; Sturla, Shana J; Marra, Giancarlo; Beerenwinkel, Niko

    2014-03-17

    Diets enriched with bioactive food components trigger molecular changes in cells that may contribute to either health-promoting or adverse effects. Recent technological advances in high-throughput data generation allow for observing systems-wide molecular responses to cellular perturbations with nontoxic and dietary-relevant doses while considering the intrinsic differences between cancerous and noncancerous cells. In this chemical profile, we compared molecular responses of the colon cancer cell line HT29 and a noncancerous colon epithelial cell line (HCEC) to two widely encountered food components, sulforaphane and selenium. We conducted this comparison by generating new transcriptome data by microarray gene-expression profiling, analyzing them statistically on the single gene, network, and functional pathway levels, and integrating them with protein expression data. Sulforaphane and selenium, at doses that did not inhibit the growth of the tested cells, induced or repressed the transcription of a limited number of genes in a manner distinctly dependent on the chemical and the cell type. The genes that most strongly responded in cancer cells were observed after treatment with sulforaphane and were members of the aldo-keto reductase (AKR) superfamily. These genes were in high agreement in terms of fold change with their corresponding proteins (correlation coefficient r(2) = 0.98, p = 0.01). Conversely, selenium had little influence on the cancer cells. In contrast, in noncancerous cells, selenium induced numerous genes involved in apoptotic, angiogenic, or tumor proliferation pathways, whereas the influence of sulforaphane was very limited. These findings contribute to defining the significance of cell type in interpreting human cellular transcriptome-level responses to exposures to natural components of the diet.

  19. Age-related gene expression analysis in enteric ganglia of human colon after laser microdissection

    Directory of Open Access Journals (Sweden)

    Susan eHetz

    2014-10-01

    Full Text Available The enteric nervous system (ENS poses the intrinsic innervation of the gastrointestinal tract and plays a critical role for all stages of postnatal life. There is increasing scientific and clinical interest in acquired or age-related gastrointestinal dysfunctions that can be manifested in diseases such as gut constipation or fecal incontinence. In this study, we sought to analyze age-dependent changes in the gene expression profile of the human ENS, particularly in the myenteric plexus. Therefore, we used the laser microdissection technique which has been proven as a feasible tool to analyze distinct cell populations within heterogeneously composed tissues.Full biopsy gut samples were prepared from children (4-12 months, middle aged (48-58 years and aged donors (70-95 years. Cryosections were histologically stained with H&E, the ganglia of the myenteric plexus identified and RNA isolated using laser microdissection technique. Quantitative PCR was performed for selected neural genes, neurotransmitters and receptors. Data were confirmed on protein level using NADPH-diaphorase staining and immunohistochemistry.As result, we demonstrate age-associated alterations in site-specific gene expression pattern of the ENS. Thus, in the adult and aged distal parts of the colon a marked decrease in relative gene expression of neural key genes like NGFR, RET, NOS1 and a concurrent increase of CHAT were observed. Further, we detected notable regional differences of RET, CHAT, TH and S100B comparing gene expression in aged proximal and distal colon. Interestingly, markers indicating cellular senescence or oxidative stress (SNCA, CASP3, CAT, SOD2 and TERT were largely unchanged within the ENS. For the first time, our study also describes the age-dependent expression pattern of all major sodium channels within the ENS.Our results are in line with previous studies showing spatio-temporal differences within the mammalian ENS.

  20. Coordinate up-regulation of low-density lipoprotein receptor and cyclo-oxygenase-2 gene expression in human colorectal cells and in colorectal adenocarcinoma biopsies

    Science.gov (United States)

    Lum, D. F.; McQuaid, K. R.; Gilbertson, V. L.; Hughes-Fulford, M.

    1999-01-01

    Many colorectal cancers have high levels of cyclo-oxygenase 2 (COX-2), an enzyme that metabolizes the essential fatty acids into prostaglandins. Since the low-density lipoprotein receptor (LDLr) is involved in the uptake of essential fatty acids, we studied the effect of LDL on growth and gene regulation in colorectal cancer cells. DiFi cells grown in lipoprotein-deficient sera (LPDS) grew more slowly than cells with LDL. LDLr antibody caused significant inhibition of tumor cell growth but did not affect controls. In addition, LDL uptake did not change in the presence of excess LDL, suggesting that ldlr mRNA lacks normal feedback regulation in some colorectal cancers. Analysis of the ldlr mRNA showed that excess LDL in the medium did not cause down-regulation of the message even after 24 hr. The second portion of the study examined the mRNA expression of ldlr and its co-regulation with cox-2 in normal and tumor specimens from patients with colorectal adenocarcinomas. The ratio of tumor:paired normal mucosa of mRNA expression of ldlr and of cox-2 was measured in specimens taken during colonoscopy. ldlr and cox-2 transcripts were apparent in 11 of 11 carcinomas. There was significant coordinate up-regulation both of ldlr and of cox-2 in 6 of 11 (55%) tumors compared with normal colonic mucosa. There was no up-regulation of cox-2 without concomitant up-regulation of ldlr. These data suggest that the LDLr is abnormally regulated in some colorectal tumors and may play a role in the up-regulation of cox-2. Copyright 1999 Wiley-Liss, Inc.

  1. The Shiga toxin 2 B subunit inhibits net fluid absorption in human colon and elicits fluid accumulation in rat colon loops

    Directory of Open Access Journals (Sweden)

    V. Pistone Creydt

    2004-06-01

    Full Text Available Shiga toxin (Stx-producing Escherichia coli (STEC colonizes the large intestine causing a spectrum of disorders, including watery diarrhea, bloody diarrhea (hemorrhagic colitis, and hemolytic-uremic syndrome. It is estimated that hemolytic-uremic syndrome is the most common cause of acute renal failure in infants in Argentina. Stx is a multimeric toxin composed of one A subunit and five B subunits. In this study we demonstrate that the Stx2 B subunit inhibits the water absorption (Jw across the human and rat colonic mucosa without altering the electrical parameters measured as transepithelial potential difference and short circuit current. The time-course Jw inhibition by 400 ng/ml purified Stx2 B subunit was similar to that obtained using 12 ng/ml Stx2 holotoxin suggesting that both, A and B subunits of Stx2 contributed to inhibit the Jw. Moreover, non-hemorrhagic fluid accumulation was observed in rat colon loops after 16 h of treatment with 3 and 30 ng/ml Stx2 B subunit. These changes indicate that Stx2 B subunit induces fluid accumulation independently of A subunit activity by altering the usual balance of intestinal absorption and secretion toward net secretion. In conclusion, our results suggest that the Stx2 B subunit, which is non-toxic for Vero cells, may contribute to the watery diarrhea observed in STEC infection. Further studies will be necessary to determine whether the toxicity of Stx2 B subunit may have pathogenic consequences when it is used as a component in an acellular STEC vaccine or as a vector in cancer vaccines.

  2. Lactobacillus gasseri Gasser AM63(T) degrades oxalate in a multistage continuous culture simulator of the human colonic microbiota.

    Science.gov (United States)

    Lewanika, Thokozile R; Reid, Sharon J; Abratt, Valerie R; Macfarlane, George T; Macfarlane, Sandra

    2007-07-01

    Colonic oxalate-degrading bacteria have been shown to play an important role in human kidney stone formation. In this study, molecular analysis of the Lactobacillus gasseri genome revealed a cluster of genes encoding putative formyl coenzyme A transferase (frc) and oxalyl coenzyme A decarboxylase (oxc) homologues, possibly involved in oxalate degradation. The ability of Lactobacillus gasseri Gasser AM63(T) to degrade oxalate was confirmed in vitro. Transcription of both genes was induced by oxalate, and reverse transcription-PCR confirmed that they were co-transcribed as an operon. A three-stage continuous culture system (CCS) inoculated with human fecal bacteria was used to model environmental conditions in the proximal and distal colons, at system retention times within the range of normal colonic transit rates (30 and 60 hours). A freeze-dried preparation of L. gasseri was introduced into the CCS under steady-state growth conditions. Short chain fatty acid analysis indicated that addition of L. gasseri to the CCS did not affect the equilibrium of the microbial ecosystem. Oxalate degradation was initiated in the first stage of the CCS, corresponding to the proximal colon, suggesting that this organism may have potential therapeutic use in managing oxalate kidney stone disease in humans.

  3. Transit time affects the community stability of Lactobacillus and Bifidobacterium species in an in vitro model of human colonic microbiotia.

    Science.gov (United States)

    Rodes, Laetitia; Paul, Arghya; Coussa-Charley, Michael; Al-Salami, Hani; Tomaro-Duchesneau, Catherine; Fakhoury, Marc; Prakash, Satya

    2011-12-01

    Retention time, which is analogous to transit time, is an index for bacterial stability in the intestine. Its consideration is of particular importance to optimize the delivery of probiotic bacteria in order to improve treatment efficacy. This study aims to investigate the effect of retention time on Lactobacilli and Bifidobacteria stability using an established in vitro human colon model. Three retention times were used: 72, 96, and 144 h. The effect of retention time on cell viability of different bacterial populations was analyzed with bacterial plate counts and PCR. The proportions of intestinal Bifidobacteria, Lactobacilli, Enterococci, Staphylococci and Clostridia populations, analyzed by plate counts, were found to be the same as that in human colonic microbiota. Retention time in the human colon affected the stability of Lactobacilli and Bifidobacteria communities, with maximum stability observed at 144 h. Therefore, retention time is an important parameter that influences bacterial stability in the colonic microbiota. Future clinical studies on probiotic bacteria formulations should take into consideration gastrointestinal transit parameters to improve treatment efficacy.

  4. Deciphering the colon cancer genes--report of the InSiGHT-Human Variome Project Workshop, UNESCO, Paris 2010.

    Science.gov (United States)

    Kohonen-Corish, Maija R J; Macrae, Finlay; Genuardi, Maurizio; Aretz, Stefan; Bapat, Bharati; Bernstein, Inge T; Burn, John; Cotton, Richard G H; den Dunnen, Johan T; Frebourg, Thierry; Greenblatt, Marc S; Hofstra, Robert; Holinski-Feder, Elke; Lappalainen, Ilkka; Lindblom, Annika; Maglott, Donna; Møller, Pål; Morreau, Hans; Möslein, Gabriela; Sijmons, Rolf; Spurdle, Amanda B; Tavtigian, Sean; Tops, Carli M J; Weber, Thomas K; de Wind, Niels; Woods, Michael O

    2011-04-01

    The Human Variome Project (HVP) has established a pilot program with the International Society for Gastrointestinal Hereditary Tumours (InSiGHT) to compile all inherited variation affecting colon cancer susceptibility genes. An HVP-InSiGHT Workshop was held on May 10, 2010, prior to the HVP Integration and Implementation Meeting at UNESCO in Paris, to review the progress of this pilot program. A wide range of topics were covered, including issues relating to genotype-phenotype data submission to the InSiGHT Colon Cancer Gene Variant Databases (chromium.liacs.nl/LOVD2/colon_cancer/home.php). The meeting also canvassed the recent exciting developments in models to evaluate the pathogenicity of unclassified variants using in silico data, tumor pathology information, and functional assays, and made further plans for the future progress and sustainability of the pilot program. © 2011 Wiley-Liss, Inc.

  5. Biosynthesis and transport of lysosomal alpha-glucosidase in the human colon carcinoma cell-line Caco-2: secretion from the apical surface

    NARCIS (Netherlands)

    Klumperman, J.; Fransen, J.A.; Boekestijn, J.C.; Oude Elferink, R.P.; Matter, K.; Hauri, H.P.; Tager, J.M.; Ginsel, L.A.

    1991-01-01

    The human adenocarcinoma cell line Caco-2 was used for studies on the biosynthesis and transport of lysosomal acid alpha-glucosidase in polarized epithelial cells. Metabolic labelling revealed that in Caco-2 cells alpha-glucosidase is synthesized as a precursor form of 110 x 10(3) Mr. This form is

  6. Biosynthesis and transport of lysosomal alpha-glucosidase in the human colon carcinoma cell line Caco-2: secretion from the apical surface

    NARCIS (Netherlands)

    Klumperman, J.; Fransen, J. A.; Boekestijn, T. C.; Oude Elferink, R. P.; Matter, K.; Hauri, H. P.; Tager, J. M.; Ginsel, L. A.

    1991-01-01

    The human adenocarcinoma cell line Caco-2 was used for studies on the biosynthesis and transport of lysosomal acid alpha-glucosidase in polarized epithelial cells. Metabolic labelling revealed that in Caco-2 cells alpha-glucosidase is synthesized as a precursor form of 110 x 10(3) Mr. This form is

  7. Thirty thousand years of human colonization in tasmania: new pleistocene dates.

    Science.gov (United States)

    Cosgrove, R

    1989-03-31

    Basal dates of 30,420 years before present (BP) from a limestone cave in the Florentine River valley and 30,840 BP from a sandstone rockshelter in the Shannon River valley on the edge of the central Tasmanian highlands indicate colonization of Tasmania 8,000 years earlier than previously thought. These data indicate that people arrived before the Bassian Bridge was exposed about 23,000 years ago and support evidence that Tasmania and Australia may have been connected intermittently during the past 50,000 years. The dates support earlier suggestions that the Tasmanian inland was an important focus for systematic occupation and exploitation by human groups and dispel a belief that the Aboriginal economy 30,000 years ago was based on littoral, lacustral, and riverine resources. The absence of megafauna at both sites points to their extinction by 30,000 years ago in Tasmania. The people inhabiting Tasmania at this time, together with those at Monte Verde in Chile, were the most southerly humans on Earth.

  8. Colonic epithelial cell expression of ICAM-1 relates to loss of surface continuity

    DEFF Research Database (Denmark)

    Vainer, Ben; Horn, Thomas; Nielsen, Ole Haagen

    2006-01-01

    . The aim of this study was to assess the ICAM-1 expression in human colonic tissue representing UC, Crohn's disease (CD), adenomas, and adenocarcinomas, with special attention to the epithelium. MATERIAL AND METHODS: Formalin-fixed and paraffin-embedded tissue from the archives of the Department...... and the nature of inflammation, the data indicate increased susceptibility of cancer cells to express ICAM-1. Epithelial and macrophage ICAM-1 might be involved in the immune surveillance and the first-line defense of the diseased colon.......OBJECTIVE: Intercellular adhesion molecule-1 (ICAM-1) is important in ulcerative colitis (UC) by mediating the arrest and further migration of neutrophils. In vitro studies have shown that colonocytes from chronically inflamed colon and cultured colon cancer cells are capable of expressing ICAM-1...

  9. Down-regulation of malignant potential by alpha linolenic acid in human and mouse colon cancer cells.

    Science.gov (United States)

    Chamberland, John P; Moon, Hyun-Seuk

    2015-03-01

    Omega-3 fatty acids (also called ω-3 fatty acis or n-3 fatty acid) are polyunsaturated fatty acids (PUFAs) with a double bond (C=C) at the third carbon atom from the end of the carbon chain. Numerous test tube and animal studies have shown that omega-3 fatty acids may prevent or inhibit the growth of cancers, suggesting that omega-3 fatty acids are important in cancer physiology. Alpha-linolenic acid (ALA) is one of an essential omega-3 fatty acid and organic compound found in seeds (chia and flaxseed), nuts (notably walnuts), and many common vegetable oils. ALA has also been shown to down-regulate cell proliferation of prostate, breast, and bladder cancer cells. However, direct evidence that ALA suppresses to the development of colon cancer has not been studied. Also, no previous studies have evaluated whether ALA may regulate malignant potential (adhesion, invasion and colony formation) in colon cancer cells. In order to address the questions above, we conducted in vitro studies and evaluated whether ALA may down-regulate malignant potential in human (HT29 and HCT116) and mouse (MCA38) colon cancer cell lines. We observed that treatment with 1-5 mM of ALA inhibits cell proliferation, adhesion and invasion in both human and mouse colon cancer cell lines. Interestingly, we observed that ALA did not decrease total colony numbers when compared to control. By contrast, we found that size of colony was significantly changed by ALA treatment when compared to control in all colon cancer cell lines. We suggest that our data enhance our current knowledge of ALA's mechanism and provide crucial information to further the development of new therapies for the management or chemoprevention of colon cancer.

  10. Extravirgin olive oil up-regulates CB₁ tumor suppressor gene in human colon cancer cells and in rat colon via epigenetic mechanisms.

    Science.gov (United States)

    Di Francesco, Andrea; Falconi, Anastasia; Di Germanio, Clara; Micioni Di Bonaventura, Maria Vittoria; Costa, Antonio; Caramuta, Stefano; Del Carlo, Michele; Compagnone, Dario; Dainese, Enrico; Cifani, Carlo; Maccarrone, Mauro; D'Addario, Claudio

    2015-03-01

    Extravirgin olive oil (EVOO) represents the typical lipid source of the Mediterranean diet, an eating habit pattern that has been associated with a significant reduction of cancer risk. Diet is the more studied environmental factor in epigenetics, and many evidences suggest dysregulation of epigenetic pathways in cancer. The aim of our study was to investigate the effects of EVOO and its phenolic compounds on endocannabinoid system (ECS) gene expression via epigenetic regulation in both human colon cancer cells (Caco-2) and rats exposed to short- and long-term dietary EVOO. We observed a selective and transient up-regulation of CNR1 gene - encoding for type 1 cannabinoid receptor (CB₁) - that was evoked by exposure of Caco-2 cells to EVOO (100 ppm), its phenolic extracts (OPE, 50 μM) or authentic hydroxytyrosol (HT, 50 μM) for 24 h. None of the other major elements of the ECS (i.e., CB₂; GPR55 and TRPV1 receptors; and NAPE-PLD, DAGL, FAAH and MAGL enzymes) was affected at any time point. The stimulatory effect of OPE and HT on CB₁ expression was inversely correlated to DNA methylation at CNR1 promoter and was associated with reduced proliferation of Caco-2 cells. Interestingly, CNR1 gene was less expressed in Caco-2 cells when compared to normal colon mucosa cells, and again this effect was associated with higher level of DNA methylation at CNR1. Moreover, in agreement with the in vitro studies, we also observed a remarkable (~4-fold) and selective increase in CB₁ expression in the colon of rats receiving dietary EVOO supplementation for 10 days. Consistently, CpG methylation of rat Cnr1 promoter, miR23a and miR-301a, previously shown to be involved in the pathogenesis of colorectal cancer and predicted to target CB₁ mRNA, was reduced after EVOO administration down to ~50% of controls. Taken together, our findings demonstrating CB₁ gene expression modulation by EVOO or its phenolic compounds via epigenetic mechanism, both in vitro and in vivo, may

  11. Human pancreatic stellate cells modulate 3D collagen alignment to promote the migration of pancreatic ductal adenocarcinoma cells.

    Science.gov (United States)

    Drifka, Cole R; Loeffler, Agnes G; Esquibel, Corinne R; Weber, Sharon M; Eliceiri, Kevin W; Kao, W John

    2016-12-01

    A hallmark of pancreatic ductal adenocarcinoma (PDAC) is the ability for cancer cells to aggressively infiltrate and navigate through a dense stroma during the metastatic process. Key features of the PDAC stroma include an abundant population of activated pancreatic stellate cells (PSCs) and highly aligned collagen fibers; however, important questions remain regarding how collagen becomes aligned and what the biological manifestations are. To better understand how PSCs, aligned collagen, and PDAC cells might cooperate during the transition to invasion, we utilized a microchannel-based in vitro tumor model and advanced imaging technologies to recreate and examine in vivo-like heterotypic interactions. We found that PSCs participate in a collaborative process with cancer cells by orchestrating the alignment of collagen fibers that, in turn, are permissive to enhanced cell migration. Additionally, direct contact between PSCs, collagen, and PDAC cells is critical to invasion and co-migration of both cell types. This suggests PSCs may accompany and assist in navigating PDAC cells through the stromal terrain. Together, our data provides a new role for PSCs in stimulating the metastatic process and underscores the importance of collagen alignment in cancer progression.

  12. Artificial Analogues of Circulating Box C/D RNAs Induce Strong Innate Immune Response and MicroRNA Activation in Human Adenocarcinoma Cells.

    Science.gov (United States)

    Stepanov, Grigory A; Filippova, Julia A; Nushtaeva, Anna A; Kuligina, Elena V; Koval, Olga A; Richter, Vladimir A; Semenov, Dmitriy V

    2016-01-01

    Fragments of small nucleolar RNAs (snoRNAs) were found among various non-coding RNAs (ncRNAs) circulating in human blood. Currently, the function of such cell-free sno-derived-RNAs is not clearly defined. This work is aimed at identifying regulatory pathways controlled by extracellular snoRNAs. In order to determine the molecular targets and pathways affected by artificial snoRNAs, we performed Illumina array analysis of MCF-7 human adenocarcinoma cells transfected with box C/D RNAs. The genes related to the innate immune response and apoptotic cascades were found to be activated in transfected cells compared with control cells. Intriguingly, the transfection of MCF-7 cells with artificial box C/D snoRNAs also increased the transcription of several microRNAs, such as mir-574, mir-599 and mir-21. Our data demonstrated that extracellular snoRNAs introduced into human cells may function as gene expression modulators, with activation of microRNA genes being one of the regulatory mechanisms.

  13. Abrupt hydroclimate disruption across the Australian arid zone 50 ka coincident with human colonization

    Science.gov (United States)

    Miller, G. H.; Fogel, M. L.; Magee, J. W.; Gagan, M. K.

    2016-12-01

    Although many studies focus on how climate change impacted ancient societies, in Australia a growing body of evidence indicates that activities of the earliest human colonizers in turn altered the Australian climate. We utilize the stable isotopes of carbon and oxygen preserved in near-continuous 100 ka time series of avian eggshell from five regions across the Australian arid zone to reconstruct ecosystem status (d13C) and effective moisture (d18O). Training sets of sub-modern samples provide the basis for the reconstructions. Together, d13C and d18O provide independent estimates of ecosystem status and climate over the past 100 ka from the same dated sample, reducing correlation uncertainties between proxies. Changes in eggshell d13C document a dramatic reduction of palatable summer-wet C4 grasses in all regions between 50 and 45 ka, that has persisted through to modern times. Continuous 100 ka records of effective moisture derived from eggshell d18O show moist conditions from 100 to 60 ka, with variable drying after 60 ka, but the strong shift toward greatest aridity is coincident with the onset of the last glacial maximum 30 ka ago, 15 ka after the observed ecosystem restructuring. Combining the d13C and d18O time-series shows that an abrupt and permanent restructuring of the moisture/ecosystem balance occurred between 50 and 45 ka. Additional studies show that most large monsoon-fed inland arid-zone lakes carried permanent water at least intermittently between 120 and 50 ka, but never experienced permanent deep-water status after 45 ka, despite a wide range of global climate states, including the early Holocene when most other monsoon systems were reinvigorated. The lack of exceptional climate shifts either locally or globally between 60 and 40 ka eliminates climate as the cause of the ecosystem restructuring and persistent lake desiccation. Collectively these data suggest the wave of human colonization across Australia in altered land surface characteristics