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1. Lifestyle, behaviour, and environmental modification for the management of patients with inflammatory bowel diseases: an International Organization for Study of Inflammatory Bowel Diseases consensus

Author

Abreu, M, Ahuja, V, Allez, M, Ananthakrishnan, A, Bemelman, W, Bernstein, C, Braun, J, Chowers, Y, Colombel, J-F, Danese, S, D'Haens, G, D'Hoore, A, Dignass, A, Dotan, I, Dubinsky, M, Ekbom, A, Fleshner, P, Gasche, C, Gassull, MA, Gearry, R, Ghosh, S, Gibson, P, Griffiths, A, Halfvarson, J, Hanauer, S, Harpaz, N, Hart, A, Hibi, T, Kamm, M, Kaplan, G, Kaser, A, Korelitz, B, Kotze, P, Koutroubakis, I, Kruis, W, Lakatos, P, Lewis, J, Lindsay, J, Loftus, E, Louis, E, Lukas, M, Magro, F, Mahadevan, U, Mantzaris, G, Mary, J-Y, McGovern, D, Moum, B, Munkholm, P, Neurath, M, Ng, S, O'Morain, C, Oresland, T, Panaccione, R, Panes, J, Panis, Y, Pemberton, J, Peyrin-Biroulet, L, Prantera, C, Rachmilewitz, D, Ran, Z, Reinisch, W, Remzi, F, Rhodes, J, Riddell, R, Rogler, G, Rubin, D, Sachar, D, Sandborn, W, Sands, B, Sartor, B, Schoelmerich, J, Schreiber, S, Siegel, C, Siegmund, B, Silverberg, M, Söderholm, J, Sood, A, Spinelli, A, Stange, E, Steinwurz, F, Targan, S, Travis, S, Turner, D, Tysk, C, Vatn, M, Vermeire, S, Watanabe, M, Yamamoto, T, Yamamoto-Furusho, J, Ananthakrishnan, Ashwin N, Kaplan, Gilaad G, Bernstein, Charles N, Burke, Kristin E, Lochhead, Paul J, Sasson, Alexa N, Agrawal, Manasi, Tiong, Jimmy Ho Tuan, Steinberg, Joshua, Kruis, Wolfgang, Steinwurz, Flavio, Ahuja, Vineet, Ng, Siew C, Rubin, David T, Colombel, Jean-Frederic, and Gearry, Richard

Published
2022
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2. Lifestyle, behaviour, and environmental modification for the management of patients with inflammatory bowel diseases: an International Organization for Study of Inflammatory Bowel Diseases consensus

Author

Ananthakrishnan, Ashwin N, primary, Kaplan, Gilaad G, additional, Bernstein, Charles N, additional, Burke, Kristin E, additional, Lochhead, Paul J, additional, Sasson, Alexa N, additional, Agrawal, Manasi, additional, Tiong, Jimmy Ho Tuan, additional, Steinberg, Joshua, additional, Kruis, Wolfgang, additional, Steinwurz, Flavio, additional, Ahuja, Vineet, additional, Ng, Siew C, additional, Rubin, David T, additional, Colombel, Jean-Frederic, additional, Gearry, Richard, additional, Abreu, M, additional, Ahuja, V, additional, Allez, M, additional, Ananthakrishnan, A, additional, Bemelman, W, additional, Bernstein, C, additional, Braun, J, additional, Chowers, Y, additional, Colombel, J-F, additional, Danese, S, additional, D'Haens, G, additional, D'Hoore, A, additional, Dignass, A, additional, Dotan, I, additional, Dubinsky, M, additional, Ekbom, A, additional, Fleshner, P, additional, Gasche, C, additional, Gassull, MA, additional, Gearry, R, additional, Ghosh, S, additional, Gibson, P, additional, Griffiths, A, additional, Halfvarson, J, additional, Hanauer, S, additional, Harpaz, N, additional, Hart, A, additional, Hibi, T, additional, Kamm, M, additional, Kaplan, G, additional, Kaser, A, additional, Korelitz, B, additional, Kotze, P, additional, Koutroubakis, I, additional, Kruis, W, additional, Lakatos, P, additional, Lewis, J, additional, Lindsay, J, additional, Loftus, E, additional, Louis, E, additional, Lukas, M, additional, Magro, F, additional, Mahadevan, U, additional, Mantzaris, G, additional, Mary, J-Y, additional, McGovern, D, additional, Moum, B, additional, Munkholm, P, additional, Neurath, M, additional, Ng, S, additional, O'Morain, C, additional, Oresland, T, additional, Panaccione, R, additional, Panes, J, additional, Panis, Y, additional, Pemberton, J, additional, Peyrin-Biroulet, L, additional, Prantera, C, additional, Rachmilewitz, D, additional, Ran, Z, additional, Reinisch, W, additional, Remzi, F, additional, Rhodes, J, additional, Riddell, R, additional, Rogler, G, additional, Rubin, D, additional, Sachar, D, additional, Sandborn, W, additional, Sands, B, additional, Sartor, B, additional, Schoelmerich, J, additional, Schreiber, S, additional, Siegel, C, additional, Siegmund, B, additional, Silverberg, M, additional, Söderholm, J, additional, Sood, A, additional, Spinelli, A, additional, Stange, E, additional, Steinwurz, F, additional, Targan, S, additional, Travis, S, additional, Turner, D, additional, Tysk, C, additional, Vatn, M, additional, Vermeire, S, additional, Watanabe, M, additional, Yamamoto, T, additional, and Yamamoto-Furusho, J, additional

Published
2022
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3. Lifestyle, behaviour, and environmental modification for the management of patients with inflammatory bowel diseases:an International Organization for Study of Inflammatory Bowel Diseases consensus

Author

Ananthakrishnan, A., Kaplan, G., Bernstein, C., Burke, Kristin E., Lochhead, Paul J., Sasson, Alexa N., Agrawal, Manasi, Tiong, Jimmy Ho Tuan, Steinberg, Joshua, Kruis, W., Steinwurz, Flavio, Ahuja, V., Ng, Siew C., Rubin, David T., Colombel, Jean Frederic, Gearry, Richard, Abreu, M., Allez, M., Bemelman, W., Braun, J., Chowers, Y., Colombel, J. F., Danese, S., D'Haens, G., D'Hoore, A., Dignass, A., Dotan, I., Dubinsky, M., Ekbom, A., Fleshner, P., Gasche, C., Gassull, M. A., Ghosh, S., Gibson, P., Griffiths, A., Halfvarson, J., Hanauer, S., Harpaz, N., Hart, A., Hibi, T., Kamm, M., Kaser, A., Korelitz, B., Kotze, P., Koutroubakis, I., Munkholm, P., Ananthakrishnan, A., Kaplan, G., Bernstein, C., Burke, Kristin E., Lochhead, Paul J., Sasson, Alexa N., Agrawal, Manasi, Tiong, Jimmy Ho Tuan, Steinberg, Joshua, Kruis, W., Steinwurz, Flavio, Ahuja, V., Ng, Siew C., Rubin, David T., Colombel, Jean Frederic, Gearry, Richard, Abreu, M., Allez, M., Bemelman, W., Braun, J., Chowers, Y., Colombel, J. F., Danese, S., D'Haens, G., D'Hoore, A., Dignass, A., Dotan, I., Dubinsky, M., Ekbom, A., Fleshner, P., Gasche, C., Gassull, M. A., Ghosh, S., Gibson, P., Griffiths, A., Halfvarson, J., Hanauer, S., Harpaz, N., Hart, A., Hibi, T., Kamm, M., Kaser, A., Korelitz, B., Kotze, P., Koutroubakis, I., and Munkholm, P.

Abstract

Environmental and lifestyle factors play an important role in the natural history of Crohn's disease and ulcerative colitis. A group of international experts from the International Organization for the Study of Inflammatory Bowel Diseases voted on a series of consensus statements to inform the management of inflammatory bowel disease (IBD). The recommendations include avoiding traditional cigarette smoking in patients with Crohn's disease or ulcerative colitis, screening for symptoms of depression, anxiety, and psychosocial stressors at diagnosis and during flares (with referral to mental health professionals when appropriate), and encouraging regular physical activity as tolerated. Patients using dietary approaches for treatment of their IBD should be encouraged to adopt diets that are best supported by evidence and involve monitoring for the objective resolution of inflammation. We recommend formal assessment for obesity and nutritional deficiencies, and patients should be encouraged to maintain a normal body-mass index. A shared decision-making approach to contraception should include the consideration of IBD-related factors, and risk factors for venous thromboembolism. Long-term or frequent use of high-dose non-steroidal anti-inflammatory drugs should be avoided. For primary prevention of disease in the offspring of patients with IBD, we recommend avoiding passive exposure to tobacco, using antibiotics judiciously, and considering breastfeeding when able.

Published
2022

10. 2011P The impact of pathological response (PR) on adjuvant chemotherapy (AC) decisions and patient outcomes in gastrointestinal cancers (GIC)

Author

Bhalla, S., primary, Zhu, H., additional, Lin, J-Y., additional, Özbek, U., additional, Wilck, E.J., additional, Chang, S., additional, Chen, X., additional, Ward, S., additional, Harpaz, N., additional, Polydorides, A., additional, Miller, W., additional, Fiel, M.I., additional, Modica, I., additional, Fan, W., additional, Zeizafoun, N., additional, and Ang, C., additional

Published
2020
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20. Molecular evidence for two forms of Crohn disease

Author

Gilberts, E.C.A.M., Greenstein, A.J., Katsel, P., Harpaz, N., and Greenstein, R.J.

Subjects
Crohn's disease -- Research, Immune response -- Analysis, Science and technology
Abstract

Molecular studies of resected intestinal tissue of control and Crohn disease (CD) patients reveal different host immune responses that confirm the existence of two different forms of CD namely perforating and nonperforating. This result confirms the previous epidemiological evidences on the existence of two CD forms. Increased interleukin (IL)-1p, IL-1ra mRNA expressions lead to the nonperforating CD which is the more benign form. Manifestation of a specific form of CD in an individual depends on host immune response.

Published
1994

23. Mutant p53 Prolongs NF-κB Activation and Promotes Chronic Inflammation and Inflammation-Associated Colorectal Cancer

Author

Cooks, T. Pateras, I. Tarcic, O. Solomon, H. Schetter, A. Wilder, S. Lozano, G. Pikarsky, E. Forshew, T. Rozenfeld, N. Harpaz, N. Itzkowitz, S. Harris, C. Rotter, V. Gorgoulis, V. Oren, M.

Abstract

The tumor suppressor p53 is frequently mutated in human cancer. Common mutant p53 (mutp53) isoforms can actively promote cancer through gain-of-function (GOF) mechanisms. We report that mutp53 prolongs TNF-α-induced NF-κB activation in cultured cells and intestinal organoid cultures. Remarkably, when exposed to dextran sulfate sodium, mice harboring a germline p53 mutation develop severe chronic inflammation and persistent tissue damage, and are highly prone to inflammation-associated colon cancer. This mutp53 GOF is manifested by rapid onset of flat dysplastic lesions that progress to invasive carcinoma with mutp53 accumulation and augmented NF-κB activation, faithfully recapitulating features frequently observed in human colitis-associated colorectal cancer (CAC). These findings might explain the early appearance of p53 mutations in human CAC. © 2013 Elsevier Inc.

Published
2013

24. A role for HB-EGF/EGFR and MAPK signaling in the development of intestinal serrated polyps in mice

Author

Bongers, G.M., Muniz, L. R., Pacer, M., Thirunarayanan, N., Smit, M.J., Reddy, E.P., Mayer, L., Furtado, G.C., Harpaz, N., Lira, SA, Medicinal chemistry, and AIMMS

Subjects
SDG 3 - Good Health and Well-being, neoplasms, digestive system diseases
Abstract

BACKGROUND & AIMS: Epithelial cancers can be initiated by activating mutations in components of the mitogen-activated protein kinase signaling pathway such as v-raf murine sarcoma viral oncogene homolog B1 (BRAF), v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS), or epidermal growth factor receptor (EGFR). Human intestinal serrated polyps are a heterogeneous group of benign lesions, but some progress to colorectal cancer. Tumors that arise from these polyps frequently contain activating mutations in BRAF or KRAS, but little is known about the role of EGFR activation in their development. METHODS: Polyp samples were obtained from adults during screening colonoscopies at Mount Sinai Hospital in New York. We measured levels of EGFR protein and phosphorylation in human serrated polyps by immunohistochemical and immunoblot analyses. We generated transgenic mice that express the ligand for EGFR, Heparin-binding EGF-like growth factor (HB-EGF), in the intestine. RESULTS: EGFR and the extracellular-regulated kinases (ERK)1/2 were phosphorylated in serrated areas of human hyperplastic polyps (HPPs), sessile serrated adenomas, and traditional serrated adenomas. EGFR and ERK1/2 were phosphorylated in the absence of KRAS or BRAF activating mutations in a subset of HPP. Transgenic expression of the EGFR ligand HB-EGF in the intestines of mice promoted development of small cecal serrated polyps. Mice that expressed a combination of HB-EGF and US28 (a constitutively active, G-proteincoupled receptor that increases processing of HB-EGF from the membrane) rapidly developed large cecal serrated polyps. These polyps were similar to HPPs and had increased phosphorylation of EGFR and ERK1/2 within the serrated epithelium. Administration of pharmacologic inhibitors of EGFR or MAPK to these transgenic mice significantly reduced polyp development. CONCLUSIONS: Activation of EGFR signaling in the intestine of mice promotes development of serrated polyps. EGFR signaling also is activated in human HPPs, sessile serrated adenomas, and traditional serrated adenomas. © 2012 AGA Institute.

Published
2012
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27. IL-23 activates innate lymphoid cells to promote neonatal intestinal pathology

Author

Chen, L., primary, He, Z., additional, Slinger, E., additional, Bongers, G., additional, Lapenda, T LS, additional, Pacer, M.E., additional, Jiao, J., additional, Beltrao, M.F., additional, Soto, A.J., additional, Harpaz, N., additional, Gordon, R.E., additional, Ochando, J.C., additional, Oukka, M., additional, Iuga, A.C., additional, Chensue, S.W., additional, Blander, J.M., additional, Furtado, G.C., additional, and Lira, S.A., additional

Published
2015
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28. The effect of mesalazine for chemoprevention in early grade dysplasia in ulcerative colitis

Author

Ullman, T.A., Croog, V., Kornbluth, A., Harpaz, N., and Itzkowitz, S.H.

Subjects
Ulcerative colitis -- Care and treatment -- Research, Mesalamine -- Health aspects -- Research, Colorectal cancer -- Care and treatment -- Research, Chemoprevention -- Health aspects -- Research, Health, Care and treatment, Research, Health aspects
Abstract

Background: Some studies suggest that mesalazine (5-ASA) can attenuate the rate of progression of ulcerative colitis (UC) to colorectal cancer (CRC). Little is known about where in the colitis-dysplasiacarcinoma sequence [...]

Published
2004

30. The cytomegalovirus-encoded chemokine receptor US28 promotes intestinal neoplasia in transgenic mice

Author

Bongers, G., Maussang, D., Muniz, L.R., Noriega, V.M., Fraile-Ramos, A., Barker, N., Marchesi, F., Thirunarayanan, N., Vischer, H.F., Qin, L., Mayer, L., Harpaz, N., Leurs, R., Furtado, G.C., Clevers, H., Tortorella, D., Smit, M.J., Lira, S.A., Bongers, G., Maussang, D., Muniz, L.R., Noriega, V.M., Fraile-Ramos, A., Barker, N., Marchesi, F., Thirunarayanan, N., Vischer, H.F., Qin, L., Mayer, L., Harpaz, N., Leurs, R., Furtado, G.C., Clevers, H., Tortorella, D., Smit, M.J., and Lira, S.A.

Abstract

US28 is a constitutively active chemokine receptor encoded by CMV (also referred to as human herpesvirus 5), a highly prevalent human virus that infects a broad spectrum of cells, including intestinal epithelial cells (IECs). To study the role of US28 in vivo, we created transgenic mice (VS28 mice) in which US28 expression was targeted to IECs. Expression of US28 was detected in all IECs of the small and large intestine, including in cells expressing leucine rich repeat containing GPCR5 (Lgr5), a marker gene of intestinal epithelial stem cells. US28 expression in IECs inhibited glycogen synthase 3beta (GSK-3beta) function, promoted accumulation of beta-catenin protein, and increased expression of Wnt target genes involved in the control of the cell proliferation. VS28 mice showed a hyperplastic intestinal epithelium and, strikingly, developed adenomas and adenocarcinomas by 40 weeks of age. When exposed to an inflammation-driven tumor model (azoxymethane/dextran sodium sulfate), VS28 mice developed a significantly higher tumor burden than control littermates. Transgenic coexpression of the US28 ligand CCL2 (an inflammatory chemokine) increased IEC proliferation as well as tumor burden, suggesting that the oncogenic activity of US28 can be modulated by inflammatory factors. Together, these results indicate that expression of US28 promotes development of intestinal dysplasia and cancer in transgenic mice and suggest that CMV infection may facilitate development of intestinal neoplasia in humans., US28 is a constitutively active chemokine receptor encoded by CMV (also referred to as human herpesvirus 5), a highly prevalent human virus that infects a broad spectrum of cells, including intestinal epithelial cells (IECs). To study the role of US28 in vivo, we created transgenic mice (VS28 mice) in which US28 expression was targeted to IECs. Expression of US28 was detected in all IECs of the small and large intestine, including in cells expressing leucine rich repeat containing GPCR5 (Lgr5), a marker gene of intestinal epithelial stem cells. US28 expression in IECs inhibited glycogen synthase 3beta (GSK-3beta) function, promoted accumulation of beta-catenin protein, and increased expression of Wnt target genes involved in the control of the cell proliferation. VS28 mice showed a hyperplastic intestinal epithelium and, strikingly, developed adenomas and adenocarcinomas by 40 weeks of age. When exposed to an inflammation-driven tumor model (azoxymethane/dextran sodium sulfate), VS28 mice developed a significantly higher tumor burden than control littermates. Transgenic coexpression of the US28 ligand CCL2 (an inflammatory chemokine) increased IEC proliferation as well as tumor burden, suggesting that the oncogenic activity of US28 can be modulated by inflammatory factors. Together, these results indicate that expression of US28 promotes development of intestinal dysplasia and cancer in transgenic mice and suggest that CMV infection may facilitate development of intestinal neoplasia in humans.

Published
2010

32. High resolution microendoscopy for classification of colorectal polyps

Author

Chang, S., additional, Shukla, R., additional, Polydorides, A., additional, Vila, P., additional, Lee, M., additional, Han, H., additional, Kedia, P., additional, Lewis, J., additional, Gonzalez, S., additional, Kim, M., additional, Harpaz, N., additional, Godbold, J., additional, Richards-Kortum, R., additional, and Anandasabapathy, S., additional

Published
2013
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33. Attenuation of TNF-driven murine ileitis by intestinal expression of the viral immunomodulator CrmD

Author

Viejo-Borbolla, A, primary, Martin, A P, additional, Muniz, L R, additional, Shang, L, additional, Marchesi, F, additional, Thirunarayanan, N, additional, Harpaz, N, additional, Garcia, R A, additional, Apostolaki, M, additional, Furtado, G C, additional, Mayer, L, additional, Kollias, G, additional, Alcami, A, additional, and Lira, S A, additional

Published
2010
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36. The leukocyte adherence inhibition test (LAI) in preoperative diagnosis of epithelial ovarian cancer

Author

A. Fink, Harpaz N, R. Dgani, U. Elchalal, Bentwich Z, and Shani A

Subjects
Adult, medicine.medical_specialty, Adolescent, Adhesion (medicine), Ovary, Gastroenterology, Preoperative care, Sensitivity and Specificity, Adnexal mass, Dinoprostone, Predictive Value of Tests, Internal medicine, Preoperative Care, medicine, Carcinoma, Tumor Cells, Cultured, Humans, Epithelial ovarian cancer, Aged, Gynecology, Aged, 80 and over, Ovarian Neoplasms, business.industry, Obstetrics and Gynecology, Leukocyte Adherence Inhibition Test, Middle Aged, medicine.disease, medicine.anatomical_structure, Oncology, Adnexal Diseases, Predictive value of tests, Female, business
Abstract

One hundred two women admitted for evaluation of an adnexal mass were tested prior to surgery by the computerized tube leukocyte adherence inhibition (LAI) assay. The test was positive in 24/35 (69%) patients, diagnosed after surgery as epithelial ovarian cancer while 50/67 (75%) of those diagnosed as benign masses were negative. Only 2/38 (5%) of normal control subjects showed a false-positive result. The LAI test described in this report showed a sensitivity of 88% and a specificity of 75% in stage I ovarian cancer; thus it may be useful for early diagnosis of ovarian malignancy.

Published
1993

39. A transforming growth factor beta 1 receptor type II mutation in ulcerative colitis-associated neoplasms

Author

Souza, RF, primary, Lei, J, additional, Yin, J, additional, Appel, R, additional, Zou, TT, additional, Zhou, X, additional, Wang, S, additional, Rhyu, MG, additional, Cymes, K, additional, Chan, O, additional, Park, WS, additional, Krasna, MJ, additional, Greenwald, BD, additional, Cottrell, J, additional, Abraham, JM, additional, Simms, L, additional, Leggett, B, additional, Young, J, additional, Harpaz, N, additional, and Meltzer, SJ, additional

Published
1997
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