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55. Canadian Arctic water system innovations for freeze protection.

Author

Johnson, Ken and McGovern, D. Farrell

Subjects
FREEZES (Meteorology), WATER distribution, WATER supply, THERMAL insulation, HEAT transfer
Abstract

The article focuses on innovations for freeze protection in the Canadian Arctic water system. Topics include the challenges of providing water distribution and sewage collection systems in the Northwest Territories and Nunavut, the history of water supply systems in the region, and various methods for freeze protection, including insulation, heat tracing, and recirculation.

Published
2023

57. CA19-9 decrease at 8 weeks as a predictor of overall survival in a randomized phase III trial (MPACT) of weekly nab-paclitaxel plus gemcitabine versus gemcitabine alone in patients with metastatic pancreatic cancer

Author

Chiorean, E. G., Von Hoff, D. D., Reni, M., Arena, F. P., Infante, J. R., Bathini, V. G., Wood, T. E., Mainwaring, P. N., Muldoon, R. T., Clingan, P., Kunzmann, V., Ramanathan, R. K., Tabernero, Josep, Goldstein, D., McGovern, D., Lu, B., Ko, A., and Universitat Autònoma de Barcelona

Subjects
0301 basic medicine, Oncology, medicine.medical_specialty, CA-19-9 Antigen, endocrine system diseases, medicine.medical_treatment, pancreatic cancer, chemotherapy, Gastroenterology, Nab -paclitaxel, 03 medical and health sciences, chemistry.chemical_compound, nab-paclitaxel, 0302 clinical medicine, Fluorodeoxyglucose F18, Predictive Value of Tests, Internal medicine, Pancreatic cancer, Metastatic pancreatic cancer, Gastrointestinal Tumors, MPACT, medicine, Chemotherapy, Humans, In patient, ddc:610, business.industry, Hematology, Original Articles, medicine.disease, CA19-9, Gemcitabine, digestive system diseases, Pancreatic Neoplasms, 030104 developmental biology, chemistry, 030220 oncology & carcinogenesis, Positron-Emission Tomography, Adenocarcinoma, Deoxycytidine, Radiopharmaceuticals, business, Tomography, X-Ray Computed, medicine.drug
Abstract

Any CA19-9 decline at week 8 and radiologic response by week 8 each predicted longer OS in both treatment arms. In the nab-P + Gem arm, the higher proportion of patients with week 8 CA19-9 decrease [82% (206/252); median OS 13.2 months] than a RECIST-defined response [16% (40/252); median OS 13.7 months] suggests that CA19-9 decline is a predictor of OS applicable to a larger population., Background A phase I/II study and subsequent phase III study (MPACT) reported significant correlations between CA19-9 decreases and prolonged overall survival (OS) with nab-paclitaxel plus gemcitabine (nab-P + Gem) treatment for metastatic pancreatic cancer (MPC). CA19-9 changes at week 8 and potential associations with efficacy were investigated as part of an exploratory analysis in the MPACT trial. Patients and methods Untreated patients with MPC (N = 861) received nab-P + Gem or Gem alone. CA19-9 was evaluated at baseline and every 8 weeks. Results Patients with baseline and week-8 CA19-9 measurements were analyzed (nab-P + Gem: 252; Gem: 202). In an analysis pooling the treatments, patients with any CA19-9 decline (80%) versus those without (20%) had improved OS (median 11.1 versus 8.0 months; P = 0.005). In the nab-P + Gem arm, patients with (n = 206) versus without (n = 46) any CA19-9 decrease at week 8 had a confirmed overall response rate (ORR) of 40% versus 13%, and a median OS of 13.2 versus 8.3 months (P = 0.001), respectively. In the Gem-alone arm, patients with (n = 159) versus without (n = 43) CA19-9 decrease at week 8 had a confirmed ORR of 15% versus 5%, and a median OS of 9.4 versus 7.1 months (P = 0.404), respectively. In the nab-P + Gem and Gem-alone arms, by week 8, 16% (40/252) and 6% (13/202) of patients, respectively, had an unconfirmed radiologic response (median OS 13.7 and 14.7 months, respectively), and 79% and 84% of patients, respectively, had stable disease (SD) (median OS 11.1 and 9 months, respectively). Patients with SD and any CA19-9 decrease (158/199 and 133/170) had a median OS of 13.2 and 9.4 months, respectively. Conclusion This analysis demonstrated that, in patients with MPC, any CA19-9 decrease at week 8 can be an early marker for chemotherapy efficacy, including in those patients with SD. CA19-9 decrease identified more patients with survival benefit than radiologic response by week 8.

Published
2016

58. Positron emission tomography response evaluation from a randomized phase III trial of weekly nab-paclitaxel plus gemcitabine versus gemcitabine alone for patients with metastatic adenocarcinoma of the pancreas

Author

Ramanathan, R. K., Goldstein, D., Korn, R. L., Arena, F. P, Moore, M., Siena, S., Teixeira, L., Tabernero, Josep, Van Laethem, J.-L., Liu, H., McGovern, D., Lu, B., Von Hoff, D. D., and Universitat Autònoma de Barcelona

Subjects
0301 basic medicine, Oncology, Male, positron emission tomography, endocrine system diseases, pancreatic cancer, metabolic response, Deoxycytidine, nab-paclitaxel, chemistry.chemical_compound, 0302 clinical medicine, Antineoplastic Combined Chemotherapy Protocols, Neoplasm Metastasis, Aged, 80 and over, medicine.diagnostic_test, Hematology, Middle Aged, medicine.anatomical_structure, Treatment Outcome, Paclitaxel, Positron emission tomography, Response Evaluation Criteria in Solid Tumors, 030220 oncology & carcinogenesis, Adenocarcinoma, Female, Pancreas, medicine.drug, Adult, medicine.medical_specialty, Nab-paclitaxel, Disease-Free Survival, Drug Administration Schedule, Nab -paclitaxel, 03 medical and health sciences, Internal medicine, Pancreatic cancer, Albumins, Gastrointestinal Tumors, medicine, Humans, Letters to the Editor, Aged, business.industry, Metabolic response, Original Articles, medicine.disease, Gemcitabine, Cancérologie, Pancreatic Neoplasms, 030104 developmental biology, chemistry, Positron-Emission Tomography, business, Hématologie
Abstract

In the phase III MPACT trial, nab-paclitaxel plus gemcitabine (nab-P + Gem) demonstrated superior efficacyversus Gem alone for patients with metastatic pancreatic cancer. We sought to examine the feasibility of positron emissiontomography (PET) and to compare metabolic response rates and associated correlations with efficacy in the MPACT trial.Patients and methods: Patients with previously untreated metastatic adenocarcinoma of the pancreas were randomized1:1 to receive nab-P + Gem or Gem alone. Treatment continued until disease progression by RECIST or unacceptable toxicity.Results: PET scans were carried out on the first 257 patients enrolled at PET-equipped centers (PET cohort). Most patients(252 of 257) had ≥ 2 PET-avid lesions, and median maximum standardized uptake values at baseline were 4.6 and 4.5 in thenab-P + Gem and Gem-alone arms, respectively. In a pooled treatment arm analysis, a metabolic response by PET (best responseat any time during study) was associated with longer overall survival (OS) (median 11.3 versus 6.9 months; HR, 0.56;P < 0.001). Efficacy results within each treatment arm appeared better for patients with a metabolic response. The metabolicresponse rate (best response and week 8 response) was higher for nab-P + Gem (best response: 72% versus 53%,P = 0.002; week 8: 67% versus 51%; P = 0.014). Efficacy in the PET cohort was greater for nab-P + Gem versus Gem alone,including for OS (median 10.5 versus 8.4 months; hazard ratio [HR], 0.71; P = 0.009) and ORR by RECIST (31% versus 11%;P < 0.001).Conclusion: Pancreatic lesions were PET avid at baseline, and the rate of metabolic response was significantly higher fornab-P + Gem versus Gem alone at week 8 and for best response during study. Having a metabolic response was associatedwith longer survival, and more patients experienced a metabolic response than a RECIST-defined response.ClinicalTrials.gov: NCT00844649., SCOPUS: ar.j, info:eu-repo/semantics/published

Published
2015

60. Dose modification and efficacy of nab-paclitaxel plus gemcitabine vs. gemcitabine for patients with metastatic pancreatic cancer: Phase III MPACT trial

Author

Scheithauer, W, Ramanathan, RK, Moore, M, Macarulla, T, Goldstein, D, Hammel, P, Kunzmann, V, Liu, H, McGovern, D, Romano, A, Von Hoff, DD, Scheithauer, W, Ramanathan, RK, Moore, M, Macarulla, T, Goldstein, D, Hammel, P, Kunzmann, V, Liu, H, McGovern, D, Romano, A, and Von Hoff, DD

Abstract

© 2016. Journal of Gastrointestinal Oncology. Background: Dose modifications following adverse events (AEs) are an important part of the management of patients with pancreatic cancer treated with chemotherapy. While dose modifications are utilized to ensure patient safety, the subsequent influence of dose adjustments on treatment exposure and efficacy have not been reported in detail. This exploratory analysis examined the influence of dose modifications on treatment exposure and efficacy in the phase III MPACT trial, which demonstrated superior efficacy of nab-paclitaxel (nab-P) plus gemcitabine (Gem) to Gem alone for the treatment of metastatic pancreatic cancer. Methods: Patients received either nab-P 125 mg/m2 + Gem 1,000 mg/m2 on days 1, 8, and 15 every 4 weeks or Gem 1,000 mg/m2 weekly for the first 7 of 8 weeks (cycle 1) and then days 1, 8, and 15 every 4 weeks (cycle ≥ 2). The protocol allowed up to 2 dose reductions per agent. Dose delays were also used to manage toxicities. Results: Toxicities that most commonly led to dose modifications were neutropenia, peripheral neuropathy, thrombocytopenia, and fatigue for nab-P and neutropenia, thrombocytopenia, and fatigue for Gem alone. Baseline characteristics were similar in patients with dose modifications and the intent-to-treat (ITT) population. Among the 421 treated patients in the nab-P + Gem arm, all patients initiated treatment at the per-protocol nab-P starting dose of 125 mg/m2; 172 (41%) had a nab-P dose reduction, and 300 (71%) had a nab-P dose delay during the study. Most dose modifications occurred after the first 3 months (2 cycles) of treatment. The majority of patients (104/172, 60%) required only 1 nab-P dose reduction, and over half of patients (163/300) had either 1 or 2 dose delays. Patients who underwent dose modifications of nab-P had greater treatment exposure than those who did not in terms of treatment duration, number of cycles administered, and cumulative dose of nab-P delivered. Overal

Published
2016

61. Positron emission tomography response evaluation from a randomized phase III trial of weekly nab-paclitaxel plus gemcitabine versus gemcitabine alone for patients with metastatic adenocarcinoma of the pancreas

Author

Ramanathan, RK, Goldstein, D, Korn, RL, Arena, F, Moore, M, Siena, S, Teixeira, L, Tabernero, J, Van Laethem, JL, Liu, H, McGovern, D, Lu, B, Von Hoff, DD, Ramanathan, RK, Goldstein, D, Korn, RL, Arena, F, Moore, M, Siena, S, Teixeira, L, Tabernero, J, Van Laethem, JL, Liu, H, McGovern, D, Lu, B, and Von Hoff, DD

Abstract

In the phase III MPACT trial, nab-paclitaxel plus gemcitabine (nab-P + Gem) demonstrated superior efficacyversus Gem alone for patients with metastatic pancreatic cancer. We sought to examine the feasibility of positron emissiontomography (PET) and to compare metabolic response rates and associated correlations with efficacy in the MPACT trial.Patients and methods: Patients with previously untreated metastatic adenocarcinoma of the pancreas were randomized1:1 to receive nab-P + Gem or Gem alone. Treatment continued until disease progression by RECIST or unacceptable toxicity.Results: PET scans were carried out on the first 257 patients enrolled at PET-equipped centers (PET cohort). Most patients(252 of 257) had ≥ 2 PET-avid lesions, and median maximum standardized uptake values at baseline were 4.6 and 4.5 in thenab-P + Gem and Gem-alone arms, respectively. In a pooled treatment arm analysis, a metabolic response by PET (best responseat any time during study) was associated with longer overall survival (OS) (median 11.3 versus 6.9 months; HR, 0.56;P < 0.001). Efficacy results within each treatment arm appeared better for patients with a metabolic response. The metabolicresponse rate (best response and week 8 response) was higher for nab-P + Gem (best response: 72% versus 53%,P = 0.002; week 8: 67% versus 51%; P = 0.014). Efficacy in the PET cohort was greater for nab-P + Gem versus Gem alone,including for OS (median 10.5 versus 8.4 months; hazard ratio [HR], 0.71; P = 0.009) and ORR by RECIST (31% versus 11%;P < 0.001).Conclusion: Pancreatic lesions were PET avid at baseline, and the rate of metabolic response was significantly higher fornab-P + Gem versus Gem alone at week 8 and for best response during study. Having a metabolic response was associatedwith longer survival, and more patients experienced a metabolic response than a RECIST-defined response.ClinicalTrials.gov: NCT00844649.

Published
2016

62. CA19-9 decrease at 8 weeks as a predictor of overall survival in a randomized phase III trial (MPACT) of weekly nab-paclitaxel plus gemcitabine versus gemcitabine alone in patients with metastatic pancreatic cancer

Author

Chiorean, EG, Von Hoff, DD, Reni, M, Arena, FP, Infante, JR, Bathini, VG, Wood, TE, Mainwaring, PN, Muldoon, RT, Clingan, PR, Kunzmann, V, Ramanathan, RK, Tabernero, J, Goldstein, D, McGovern, D, Lu, B, Ko, A, Chiorean, EG, Von Hoff, DD, Reni, M, Arena, FP, Infante, JR, Bathini, VG, Wood, TE, Mainwaring, PN, Muldoon, RT, Clingan, PR, Kunzmann, V, Ramanathan, RK, Tabernero, J, Goldstein, D, McGovern, D, Lu, B, and Ko, A

Abstract

Background: A phase I/II study and subsequent phase III study (MPACT) reported significant correlations between CA19-9 decreases and prolonged overall survival (OS) with nab-paclitaxel plus gemcitabine (nab-P + Gem) treatment for metastatic pancreatic cancer (MPC). CA19-9 changes at week 8 and potential associations with efficacy were investigated as part of an exploratory analysis in the MPACT trial. Patients and methods: Untreated patients with MPC (N = 861) received nab-P + Gem or Gem alone. CA19-9 was evaluated at baseline and every 8 weeks. Results: Patients with baseline and week-8 CA19-9 measurements were analyzed (nab-P + Gem: 252; Gem: 202). In an analysis pooling the treatments, patients with any CA19-9 decline (80%) versus those without (20%) had improved OS (median 11.1 versus 8.0 months; P = 0.005). In the nab-P + Gem arm, patients with (n = 206) versus without (n = 46) any CA19-9 decrease at week 8 had a confirmed overall response rate (ORR) of 40% versus 13%, and a median OS of 13.2 versus 8.3 months (P = 0.001), respectively. In the Gem-alone arm, patients with (n = 159) versus without (n = 43) CA19- 9 decrease at week 8 had a confirmed ORR of 15% versus 5%, and a median OS of 9.4 versus 7.1 months (P = 0.404), respectively. In the nab-P + Gem and Gem-alone arms, by week 8, 16% (40/252) and 6% (13/202) of patients, respectively, had an unconfirmed radiologic response (median OS 13.7 and 14.7 months, respectively), and 79% and 84% of patients, respectively, had stable disease (SD) (median OS 11.1 and 9 months, respectively). Patients with SD and any CA19-9 decrease (158/199 and 133/170) had a median OS of 13.2 and 9.4 months, respectively. Conclusion: This analysis demonstrated that, in patients with MPC, any CA19-9 decrease at week 8 can be an early marker for chemotherapy efficacy, including in those patients with SD. CA19-9 decrease identified more patients with survival benefit than radiologic response by week 8.

Published
2016

63. Looking beyond symptoms and disease activity to define disease severity in inflammatory bowel disease: results of an IOIBD specialist panel

Author

Siegel, C., Whitman, C., Spiegel, B., Feagan, B., Sands, B., Loftus, E., Panaccione, R., D'Haens, G., Bernstein, C., Gearry, R., Ng, S., Mantzaris, G., Sartor, B., Silverberg, M., Riddell, R., Koutroubakis, I., O'Morain, C., Lakatos, P., McGovern, D., Halfvarson, J., Reinisch, W., Rogler, G., Kruis, W., Tysk, C., Schreiber, S., Danese, S., Sandborn, W., Griffiths, A., Moum, B., Gasche, C., Pallone, F., Travis, S., Panes, J., Colombel, J. -F., Hanauer, S., Peyrin-Biroulet, L., Siegel, C., Whitman, C., Spiegel, B., Feagan, B., Sands, B., Loftus, E., Panaccione, R., D'Haens, G., Bernstein, C., Gearry, R., Ng, S., Mantzaris, G., Sartor, B., Silverberg, M., Riddell, R., Koutroubakis, I., O'Morain, C., Lakatos, P., McGovern, D., Halfvarson, J., Reinisch, W., Rogler, G., Kruis, W., Tysk, C., Schreiber, S., Danese, S., Sandborn, W., Griffiths, A., Moum, B., Gasche, C., Pallone, F., Travis, S., Panes, J., Colombel, J. -F., Hanauer, S., and Peyrin-Biroulet, L.

Published
2016

64. Positron emission tomography response evaluation from a randomized phase III trial of weekly nab-paclitaxel plus gemcitabine versus gemcitabine alone for patients with metastatic adenocarcinoma of the pancreas

Author

Ramanathan, Ramesh R.K., Liu, Helen, McGovern, D, Lu, Brian, Von Hoff, Daniel D.D., Goldstein, David, Korn, Ronald R.L., Arena, Francis F.P., Moore, Malcolm J, Siena, Salvatore, Teixeira, Luis, Tabernero, Josep, Van Laethem, Jean-Luc, Ramanathan, Ramesh R.K., Liu, Helen, McGovern, D, Lu, Brian, Von Hoff, Daniel D.D., Goldstein, David, Korn, Ronald R.L., Arena, Francis F.P., Moore, Malcolm J, Siena, Salvatore, Teixeira, Luis, Tabernero, Josep, and Van Laethem, Jean-Luc

Abstract

In the phase III MPACT trial, nab-paclitaxel plus gemcitabine (nab-P + Gem) demonstrated superior efficacyversus Gem alone for patients with metastatic pancreatic cancer. We sought to examine the feasibility of positron emissiontomography (PET) and to compare metabolic response rates and associated correlations with efficacy in the MPACT trial.Patients and methods: Patients with previously untreated metastatic adenocarcinoma of the pancreas were randomized1:1 to receive nab-P + Gem or Gem alone. Treatment continued until disease progression by RECIST or unacceptable toxicity.Results: PET scans were carried out on the first 257 patients enrolled at PET-equipped centers (PET cohort). Most patients(252 of 257) had ≥ 2 PET-avid lesions, and median maximum standardized uptake values at baseline were 4.6 and 4.5 in thenab-P + Gem and Gem-alone arms, respectively. In a pooled treatment arm analysis, a metabolic response by PET (best responseat any time during study) was associated with longer overall survival (OS) (median 11.3 versus 6.9 months; HR, 0.56;P < 0.001). Efficacy results within each treatment arm appeared better for patients with a metabolic response. The metabolicresponse rate (best response and week 8 response) was higher for nab-P + Gem (best response: 72% versus 53%,P = 0.002; week 8: 67% versus 51%; P = 0.014). Efficacy in the PET cohort was greater for nab-P + Gem versus Gem alone,including for OS (median 10.5 versus 8.4 months; hazard ratio [HR], 0.71; P = 0.009) and ORR by RECIST (31% versus 11%;P < 0.001).Conclusion: Pancreatic lesions were PET avid at baseline, and the rate of metabolic response was significantly higher fornab-P + Gem versus Gem alone at week 8 and for best response during study. Having a metabolic response was associatedwith longer survival, and more patients experienced a metabolic response than a RECIST-defined response.ClinicalTrials.gov: NCT00844649., SCOPUS: ar.j, info:eu-repo/semantics/published

Published
2016

65. 682P - Phase III, international, multicenter, randomized, open-label trial of adjuvant nab-paclitaxel plus gemcitabine (nab-P/G) vs gemcitabine (G) alone for surgically resected pancreatic adenocarcinoma (APACT): Subgroup analyses

Author

Tempero, M.A., Reni, M., Riess, H., O’Reilly, E.M., Krishnamurthi, S., Österlund, P., Ales-Diaz, I.C., Milella, M., Siena, S., Tabernero, J., Van Cutsem, E., Philip, P.A., Goldstein, D., Berlin, J.D., Li, M., Ferrara, S., Bruchec, Y Le, McGovern, D., and Biankin, A.

Published
2019
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66. RAPID ASSESSMENT OF THE JAUNDICED PATIENT: THE JAUNDICE HOTLINE

Author

Mitchell, J., Hussaini, S.H., McGovern, D., Masketli, G., Farrowl, R, and Dalton, H.R.

Subjects
Gastrointestinal diseases -- Research, Health, Research
Abstract

J. Mitchell [1] S.H. Hussaini [1] D. McGovern [2] G. Masketli [1] R Farrowl [1] H.R. Dalton [1] (1.) Gascroenrerology Unit, Royal Cornwall Hospital, Treliske, Trura; (2.) John Radcliffe Hospital, [...]

Published
2001

69. A validated web-based tool to display individualised Crohn's disease predicted outcomes based on clinical, serologic and genetic variables

Author

Siegel, C. A., primary, Horton, H., additional, Siegel, L. S., additional, Thompson, K. D., additional, Mackenzie, T., additional, Stewart, S. K., additional, Rice, P. W., additional, Stempak, J. M., additional, Dezfoli, S., additional, Haritunians, T., additional, Levy, A., additional, Baek, M., additional, Milgrom, R., additional, Dulai, P. S., additional, Targan, S. R., additional, Silverberg, M. S., additional, Dubinsky, M. C., additional, and McGovern, D. P., additional

Published
2015
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70. Irish gerontological society: Proceedings of the Irish gerontological society annual scientific meeting 1988

Author

Kelly, J. F., McCullagh, P., Taggart, H. McA, Waddington, John L., O’Callaghan, Eadbhard, Larkin, Conall, O’Neill, D., Rowan, M., Abraham, D., Feely, J., Walsh, J. B., Coakley, D., O’Riordain, D. S., O’Dwyer, P. J., O’Higgins, N. J., Carr, B. M., Mulvihill, E., Keane, C., Dinneen, S., O’Sullivan, J., O’Driscoll, D., Erwin, J., Keane, E. M., Rochford, A., McGovern, D., Cox, J., Kenny, R. A., Mee, F., Atkins, N., O’Malley, K., O’Brien, E., Carr, B., Duggan, J., Kilfeather, S., Flanagan, P. G., Davies, P. G., Stout, R. W., O’Shea, B., Cox, J. P., Cox, T., England, R., McCormack, P. M. E., Smith, S., Moroney, C., Boyce, C., Hamilton, M., McElroy, J. G., and Beirne, J. A. F.

Published
1989
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72. Deep resequencing of GWAS loci identifies rare variants in CARD9, IL23R and RNF186 that are associated with ulcerative colitis

Author

Beaudoin, Melissa, Goyette, Philippe, Goel, Gautam, Louis, E., Mansfield, J. C., Mathew, C. G., McGovern, D. P., Mitrovic, M., Montgomery, G. W., Mowat, C., Newman, W., Palmieri, O., Panés, J., Lagace, Caroline, Parkes, M., Phillips, A., Ponsioen, C. Y., Potocnik, U., Prescott, N. J., Proctor, D. D., Radford-Smith, G. L., Regueiro, M., Rioux, J. D., Roberts, R., Annese, Vito, Rotter, J. I., Rutgeerts, P., Sanderson, J., Sans, M., Satsangi, J., Schreiber, S., Schumm, P., Seibold, F., Sharma, Y., Silverberg, M. S., Bitton, Alain, Simms, L. A., Steinhart, A., Targan, S. R., Taylor, K. D., Torkvist, L., Vermeire, S., Halfvarson, J., Verspaget, H. W., De Vos, M., Walters, T., Begun, Jakob, Wang, K., Weersma, R. K., Whiteman, D., Wijmenga, C., Brant, Steven R., Bresso, Francesca, Cho, Judy H., Duerr, Richard H., Halfvarson, Jonas, Boucher, Gabrielle, McGovern, Dermot P. B., Radford-Smith, Graham, Schreiber, Stefan, Schumm, Philip L., Sharma, Yashoda, Silverberg, Mark S., Weersma, Rinse K., Quebec IBD Genetics Consortium, NIDDK IBD Genetics Consortium, International IBD Genetics Consortium (IIBDGC), Lo, Ken Sin, D'Amato, Mauro, Vermeire, Severine, Franke, Andre, Lettre, Guillaume, Xavier, Ramnik J., Daly, Mark J., Rioux, John D., Aumais, G., Bernard, E. J., Bitton, A., Rivas, Manuel A., Cohen, A., Deslandres, C., Lahaie, R., Paré, P., Brant, S. R., Cho, J. H., Duerr, R. H., Stevens, Christine, Ahmad, T., Anderson, C. A., Annese, V., Baldassano, R. N., Balschun, T., Barclay, M., Barrett, J. C., Bayless, T. M., Bis, J. C., Alikashani, Azadeh, Brand, S., Bumpstead, S., Buning, C., Colombel, J. F., Cottone, M., D'Amato, M., D'Inca, R., Ladouceur, Martin, Daly, M. J., Denson, T., Dubinsky, M., Edwards, C., Ellinghaus, D., Florin, T., Franchimont, D., Franke, A., Gearry, R., Ellinghaus, David, Georges, M., Glas, J., Van Gossum, A., Griffiths, A. M., Guthery, S. L., Hakonarson, H., Haritunians, T., Hugot, J. P., de Jong, D. J., Jostins, L., Torkvist, Leif, Kugathasan, S., Kullak-Ublick, G., Latiano, A., Laukens, D., Lawrance, I., Lee, J., Lees, C. W., Lemann, M., Levine, A., Libioulle, C., and Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI)

Subjects
Cancer Research, Génétique clinique, LIVER, Genome-wide association study, Inflammatory bowel disease, 0302 clinical medicine, Crohn Disease, GENETIC-VARIANTS, Medicine and Health Sciences, Ethnicity, UBIQUITIN LIGASES, Genetics(clinical), Genetics (clinical), Genetics, 0303 health sciences, Ecology, High-Throughput Nucleotide Sequencing, CROHN-DISEASE, CROHNS-DISEASE, 3. Good health, 030220 oncology & carcinogenesis, Medical genetics, Biologie, Research Article, EXPRESSION, medicine.medical_specialty, Canada, lcsh:QH426-470, SUSCEPTIBILITY LOCI, Evolution, Ubiquitin-Protein Ligases, Ethnic Groups, Evolution des espèces, Biology, Molecular gastro-enterology and hepatology Pathogenesis and modulation of inflammation [IGMD 2], Polymorphism, Single Nucleotide, 03 medical and health sciences, Behavior and Systematics, medicine, Humans, Genetic Predisposition to Disease, Ligase activity, MODULATION, Allele, GENOME-WIDE ASSOCIATION, Molecular Biology, Genotyping, Ecology, Evolution, Behavior and Systematics, 030304 developmental biology, Genetic association, Ecologie, Biologie moléculaire, Receptors, Interleukin, medicine.disease, NUCLEAR FACTOR 4-ALPHA, Genetic architecture, Cancérologie, CARD Signaling Adaptor Proteins, lcsh:Genetics, CELLS, Colitis, Ulcerative, INTESTINAL EPITHELIAL-CELLS, Genome-Wide Association Study, INFLAMMATORY-BOWEL-DISEASE
Abstract

Genome-wide association studies and follow-up meta-analyses in Crohn's disease (CD) and ulcerative colitis (UC) have recently identified 163 disease-associated loci that meet genome-wide significance for these two inflammatory bowel diseases (IBD). These discoveries have already had a tremendous impact on our understanding of the genetic architecture of these diseases and have directed functional studies that have revealed some of the biological functions that are important to IBD (e.g. autophagy). Nonetheless, these loci can only explain a small proportion of disease variance (~14% in CD and 7.5% in UC), suggesting that not only are additional loci to be found but that the known loci may contain high effect rare risk variants that have gone undetected by GWAS. To test this, we have used a targeted sequencing approach in 200 UC cases and 150 healthy controls (HC), all of French Canadian descent, to study 55 genes in regions associated with UC. We performed follow-up genotyping of 42 rare non-synonymous variants in independent case-control cohorts (totaling 14,435 UC cases and 20,204 HC). Our results confirmed significant association to rare non-synonymous coding variants in both IL23R and CARD9, previously identified from sequencing of CD loci, as well as identified a novel association in RNF186. With the exception of CARD9 (OR = 0.39), the rare non-synonymous variants identified were of moderate effect (OR = 1.49 for RNF186 and OR = 0.79 for IL23R). RNF186 encodes a protein with a RING domain having predicted E3 ubiquitin-protein ligase activity and two transmembrane domains. Importantly, the disease-coding variant is located in the ubiquitin ligase domain. Finally, our results suggest that rare variants in genes identified by genome-wide association in UC are unlikely to contribute significantly to the overall variance for the disease. Rather, these are expected to help focus functional studies of the corresponding disease loci. © 2013 Beaudoin et al., 0, SCOPUS: ar.j, info:eu-repo/semantics/published

Published
2013

84. Nab-Paclitaxel (Nab-P) Plus Gemcitabine (Gem) Vs Gem Alone for Patients (Pts) with Metastatic Pancreatic Cancer (Pc): Subgroup Analyses of the Mpact Trial Based on the Presence of Liver Metastases (Lms) and Number of Metastatic Sites

Author

Weekes, C., primary, Parnis, F., additional, Thaler, J., additional, Prenen, H., additional, Letourneau, R., additional, Raymond, E., additional, Santoro, A., additional, Garcia-Carbonero, R., additional, Weis, J., additional, Romano, A., additional, McGovern, D., additional, Penenberg, D., additional, and Von Hoff, D.D., additional

Published
2014
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86. OP017 Cross-disease study determines extent of sharing of associated loci between five seronegative auto-inflammatory diseases

Author

Ellinghaus, D., primary, Jostins, L., additional, Cortes, A., additional, Andreassen, O., additional, Wang, Y., additional, Spain, S., additional, Elder, J., additional, Trembath, R., additional, Barker, J., additional, Karlsen, T., additional, Dale, A., additional, McGovern, D., additional, Schreiber, S., additional, Brown, M., additional, Barrett, J., additional, Parkes, M., additional, and Franke, A., additional

Published
2014
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91. Genetic variants in the region harbouring IL2/IL21 associated with ulcerative colitis.

Author

Festen, E.A., Goyette, P., Scott, R., Annese, V., Zhernakova, A., Lian, J., Lefebvre, C., Brant, S.R., Cho, J.H., Silverberg, M.S., Taylor, K.D., Jong, D.J. de, Stokkers, P.C., Mcgovern, D., Palmieri, O., Achkar, J.P., Xavier, R.J., Daly, M.J., Duerr, R.H., Wijmenga, C., Weersma, R.K., Rioux, J.D., Festen, E.A., Goyette, P., Scott, R., Annese, V., Zhernakova, A., Lian, J., Lefebvre, C., Brant, S.R., Cho, J.H., Silverberg, M.S., Taylor, K.D., Jong, D.J. de, Stokkers, P.C., Mcgovern, D., Palmieri, O., Achkar, J.P., Xavier, R.J., Daly, M.J., Duerr, R.H., Wijmenga, C., Weersma, R.K., and Rioux, J.D.

Abstract

Item does not contain fulltext, OBJECTIVES: Genetic susceptibility is known to play a large part in the predisposition to the inflammatory bowel diseases (IBDs) known as Crohn's disease (CD) and ulcerative colitis (UC). The IL2/IL21 locus on 4q27 is known to be a common risk locus for inflammatory disease (shown in coeliac disease, type 1 diabetes, rheumatoid arthritis, systemic lupus erythematosus and psoriasis), while the roles that interleukin 2 (IL2) and IL21 play in the immune response also make them attractive candidates for IBD. The objective of this study was to test for association between the IL2/IL21 locus and the IBDs. METHODS: The four single nucleotide polymorphisms (SNPs) in the IL2/IL21 locus most associated with coeliac disease were genotyped in 1590 subjects with IBD and 929 controls from The Netherlands, and then replicated in a North American cohort (2387 cases and 1266 controls) and an Italian cohort (805 cases and 421 controls), yielding a total of 4782 cases (3194 UC, 1588 CD) and 2616 controls. Allelic association testing and a pooled analysis using a Cochran-Mantel-Haenszel test were performed. RESULTS: All four SNPs were strongly associated with UC in all three cohorts and reached genome-wide significance in the pooled analysis (rs13151961 p = 1.35 x 10(-10), rs13119723 p = 8.60 x 10(-8), rs6840978 p = 3.0 7x 10(-8), rs6822844 p = 2.77 x 10(-9)). A moderate association with CD was also found in the pooled analysis (p value range 0.0016-9.86 x 10(-5)). CONCLUSIONS: A strong association for the IL2/IL21 locus with UC was found, which also confirms it as a general susceptibility locus for inflammatory disease.

Published
2009

92. Common variants at five new loci associated with early-onset inflammatory bowel disease.

Author

Imielinski, M, Baldassano, RN, Griffiths, Anne, Russell, RK, Annese, V, Dubinsky, M, Kugathasan, S, Bradfield, JP, Walters, TD, Sleiman, P, Kim, CE, Muise, A, Wang, K, Glessner, JT, Saeed, S, Zhang, H, Frackelton, EC, Hou, C, Flory, JH, Otieno, G, Chiavacci, RM, Grundmeier, R, Castro, Massimo, Latiano, A, Dallapiccola, B, Stempak, J, Abrams, DJ, Taylor, K, McGovern, D, Western Regional Alliance for Pediatric IBD, Silber, G, Wrobel, I, Quiros, A, International IBD Genetics Consortium, Barrett, J Carl, Hansoul, Sarah, Nicolae, DL, Cho, Judy H, Duerr, R H, Rioux, J D, Brant, S R, Silverberg, M S, Taylor, Kent D, Barmuda, MM, Bitton, A, Dassopoulos, T, Datta, LW, Green, T, Griffiths, Anne-Marie, Kistner, EO, Murtha, MT, Regueiro, Miguel, Rotter, J I, Schumm, L Philip, Steinhart, A H, Targan, SR, Xavier, RJ, NIDDK IBD Genetics Consortium, Libioulle, C, Sandor, Cynthia, Lathrop, Mark, Belaiche, Jacques, Gut, Ivo, Heath, Simon, Laukens, Debby, Mni, Myriam, Rutgeerts, Paul, Van Gossum, André, Zelenika, Diana, Franchimont, Denis, Hugot, JP, De Vos, M, Vermeire, Séverine, Louis, Edouard, Belgian-French IBD Consortium,, Wellcome Trust Case Control Consortium,, Cardon, LR, Anderson, CA, Drummond, H, Nimmo, Elaine R, Ahmad, T, Prescott, NJ, Onnie, CM, Fisher, SA, Marchini, J, Ghori, J, Bumpstead, S, Gwillam, R, Tremelling, M, Delukas, P, Mansfeld, J., Jewell, D, Satsangi, Jack, Mathew, CG, Parkes, M, Georges, M., Daly, M J, Heyman, MB, Ferry, GD, Kirschner, B, Lee, J, Essers, J, Grand, R, Stephens, M, Levine, A, Piccoli, D, Van Limbergen, J, Cucchiara, Salvatore, Monos, DS, Guthery, SL, Denson, L, Wilson, DC, Grant, SF, Dewit, Olivier, Imielinski, M, Baldassano, RN, Griffiths, Anne, Russell, RK, Annese, V, Dubinsky, M, Kugathasan, S, Bradfield, JP, Walters, TD, Sleiman, P, Kim, CE, Muise, A, Wang, K, Glessner, JT, Saeed, S, Zhang, H, Frackelton, EC, Hou, C, Flory, JH, Otieno, G, Chiavacci, RM, Grundmeier, R, Castro, Massimo, Latiano, A, Dallapiccola, B, Stempak, J, Abrams, DJ, Taylor, K, McGovern, D, Western Regional Alliance for Pediatric IBD, Silber, G, Wrobel, I, Quiros, A, International IBD Genetics Consortium, Barrett, J Carl, Hansoul, Sarah, Nicolae, DL, Cho, Judy H, Duerr, R H, Rioux, J D, Brant, S R, Silverberg, M S, Taylor, Kent D, Barmuda, MM, Bitton, A, Dassopoulos, T, Datta, LW, Green, T, Griffiths, Anne-Marie, Kistner, EO, Murtha, MT, Regueiro, Miguel, Rotter, J I, Schumm, L Philip, Steinhart, A H, Targan, SR, Xavier, RJ, NIDDK IBD Genetics Consortium, Libioulle, C, Sandor, Cynthia, Lathrop, Mark, Belaiche, Jacques, Gut, Ivo, Heath, Simon, Laukens, Debby, Mni, Myriam, Rutgeerts, Paul, Van Gossum, André, Zelenika, Diana, Franchimont, Denis, Hugot, JP, De Vos, M, Vermeire, Séverine, Louis, Edouard, Belgian-French IBD Consortium,, Wellcome Trust Case Control Consortium,, Cardon, LR, Anderson, CA, Drummond, H, Nimmo, Elaine R, Ahmad, T, Prescott, NJ, Onnie, CM, Fisher, SA, Marchini, J, Ghori, J, Bumpstead, S, Gwillam, R, Tremelling, M, Delukas, P, Mansfeld, J., Jewell, D, Satsangi, Jack, Mathew, CG, Parkes, M, Georges, M., Daly, M J, Heyman, MB, Ferry, GD, Kirschner, B, Lee, J, Essers, J, Grand, R, Stephens, M, Levine, A, Piccoli, D, Van Limbergen, J, Cucchiara, Salvatore, Monos, DS, Guthery, SL, Denson, L, Wilson, DC, Grant, SF, and Dewit, Olivier

Abstract

The inflammatory bowel diseases (IBD) Crohn's disease and ulcerative colitis are common causes of morbidity in children and young adults in the western world. Here we report the results of a genome-wide association study in early-onset IBD involving 3,426 affected individuals and 11,963 genetically matched controls recruited through international collaborations in Europe and North America, thereby extending the results from a previous study of 1,011 individuals with early-onset IBD. We have identified five new regions associated with early-onset IBD susceptibility, including 16p11 near the cytokine gene IL27 (rs8049439, P = 2.41 x 10(-9)), 22q12 (rs2412973, P = 1.55 x 10(-9)), 10q22 (rs1250550, P = 5.63 x 10(-9)), 2q37 (rs4676410, P = 3.64 x 10(-8)) and 19q13.11 (rs10500264, P = 4.26 x 10(-10)). Our scan also detected associations at 23 of 32 loci previously implicated in adult-onset Crohn's disease and at 8 of 17 loci implicated in adult-onset ulcerative colitis, highlighting the close pathogenetic relationship between early- and adult-onset IBD., Journal Article, Research Support, N.I.H. Extramural, Research Support, Non-U.S. Gov't, info:eu-repo/semantics/published

Published
2009

94. P687 Genetic associations with high-grade dysplasia and colorectal cancer in patients with colonic inflammatory bowel disease: preliminary results from ImmunoChip using a targeted analytic approach

Author

Waterman, M., primary, Knight, J., additional, Stempak, J., additional, Krishnaprasad, K., additional, Cleynen, I., additional, Vermeire, S., additional, Schumm, P., additional, McGovern, D., additional, Brant, S., additional, Radford-Smith, G., additional, and Silverberg, M., additional

Published
2013
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95. Cytologic Diagnosis of Heterobilharzia americana Infection in a Liver Aspirate From a Dog.

Author

Le Donne, V., McGovern, D. A., Fletcher, J. M., and Grasperge, B. J.

Subjects
DOG parasites, SCHISTOSOMATIDAE, HOSTS (Biology), HYPERCALCEMIA, WEIGHT loss
Abstract

Heterobilharzia americana is a trematode of the Schistosomatidae family that infects dogs, raccoons, and other mammals as definitive hosts. This parasite is considered endemic in the southern Atlantic and Gulf coasts; however, only a few cases are reported. A 7-year-old dog from Louisiana was referred for persistent hypercalcemia, hyperglobulinemia, and weight loss. Abdominal ultrasound revealed diffuse hyperechogenicity of the liver with several hyperechoic nodules of varying size. Cytologic examination of fine-needle aspirates of the liver revealed few ovoid to round basophilic thin-walled eggshell fragments and rare ciliated miracidia. H. americana eggs were identified on fecal sedimentation. [ABSTRACT FROM AUTHOR]

Published
2016
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99. Variants in ZNF365 isoform D are associated with Crohn's disease

Author

Haritunians, T., primary, Jones, M. R., additional, McGovern, D. P. B., additional, Shih, D. Q., additional, Barrett, R. J., additional, Derkowski, C., additional, Dubinsky, M. C., additional, Dutridge, D., additional, Fleshner, P. R., additional, Ippoliti, A., additional, King, L., additional, Leshinsky-Silver, E., additional, Levine, A., additional, Melmed, G. Y., additional, Mengesha, E., additional, Vasilauskas, E. A., additional, Ziaee, S., additional, Rotter, J. I., additional, Targan, S. R., additional, and Taylor, K. D., additional

Published
2011
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