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JOURNAL ARTICLE
Matthew B Yurgelun, Matthew H Kulke, Charles S Fuchs, Brian A Allen, Hajime Uno, Jason L Hornick, Chinedu I Ukaegbu, Lauren K Brais, Philip G McNamara, Robert J Mayer, Deborah Schrag, Jeffrey A Meyerhardt, Kimmie Ng, John Kidd, Nanda Singh, Anne-Renee Hartman, Richard J Wenstrup, Sapna Syngal
Purpose Hereditary factors play an important role in colorectal cancer (CRC) risk, yet the prevalence of germline cancer susceptibility gene mutations in patients with CRC unselected for high-risk features (eg, early age at diagnosis, personal/family history of cancer or polyps, tumor microsatellite instability [MSI], mismatch repair [MMR] deficiency) is unknown. Patients and Methods We recruited 1,058 participants who received CRC care in a clinic-based setting without preselection for age at diagnosis, personal/family history, or MSI/MMR results...
April 1, 2017: Journal of Clinical Oncology
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JOURNAL ARTICLE
Arezou A Ghazani, Nelly M Oliver, Joseph P St Pierre, Andrea Garofalo, Irene R Rainville, Elaine Hiller, Daniel J Treacy, Vanesa Rojas-Rudilla, Sam Wood, Elizabeth Bair, Michael Parello, Franklin Huang, Marios Giannakis, Frederick H Wilson, Elizabeth H Stover, Steven M Corsello, Tom Nguyen, Huma Q Rana, Alanna J Church, Carol Lowenstein, Carrie Cibulskis, Ali Amin-Mansour, Jennifer Heng, Lauren Brais, Abigail Santos, Patrick Bauer, Amanda Waldron, Peter Lo, Megan Gorman, Christine A Lydon, Marisa Welch, Philip McNamara, Stacey Gabriel, Lynette M Sholl, Neal I Lindeman, Judy E Garber, Steven Joffe, Eliezer M Van Allen, Stacy W Gray, Pasi A Ja Nne, Levi A Garraway, Nikhil Wagle
PURPOSE: Implementing cancer precision medicine in the clinic requires assessing the therapeutic relevance of genomic alterations. A main challenge is the systematic interpretation of whole-exome sequencing (WES) data for clinical care. METHODS: One hundred sixty-five adults with metastatic colorectal and lung adenocarcinomas were prospectively enrolled in the CanSeq study. WES was performed on DNA extracted from formalin-fixed paraffin-embedded tumor biopsy samples and matched blood samples...
July 2017: Genetics in Medicine: Official Journal of the American College of Medical Genetics
#43
JOURNAL ARTICLE
Association Between Somatostatin Receptor Expression and Clinical Outcomes in Neuroendocrine Tumors.
Zhi Rong Qian, Tingting Li, Monica Ter-Minassian, Juhong Yang, Jennifer A Chan, Lauren K Brais, Yohei Masugi, Arunthathi Thiaglingam, Nichole Brooks, Reiko Nishihara, Mireille Bonnemarie, Atsuhiro Masuda, Kentaro Inamura, Sun A Kim, Kosuke Mima, Yasutaka Sukawa, Ruoxu Dou, Xihong Lin, David C Christiani, Fabien Schmidlin, Charles S Fuchs, Umar Mahmood, Shuji Ogino, Matthew H Kulke
OBJECTIVE: Somatostatin receptors (SSTRs), products of gene superfamily SSTR1-5, are commonly expressed in neuroendocrine tumors (NETs). Somatostatin analogs (SSAs) bind to SSTRs and are used as therapeutic agents in patients with advanced NETs. We hypothesized that tumor SSTR expression status would be associated with clinical outcomes in NET. METHODS: Expression of the 5 SSTRs was evaluated by immunohistochemistry, using tissue microarrays comprising 173 primary NETs, 24 matched metastases, and 22 metastatic NETs from 195 patients...
November 2016: Pancreas
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JOURNAL ARTICLE
Mingfeng Zhang, Zhaoming Wang, Ofure Obazee, Jinping Jia, Erica J Childs, Jason Hoskins, Gisella Figlioli, Evelina Mocci, Irene Collins, Charles C Chung, Christopher Hautman, Alan A Arslan, Laura Beane-Freeman, Paige M Bracci, Julie Buring, Eric J Duell, Steven Gallinger, Graham G Giles, Gary E Goodman, Phyllis J Goodman, Aruna Kamineni, Laurence N Kolonel, Matthew H Kulke, Núria Malats, Sara H Olson, Howard D Sesso, Kala Visvanathan, Emily White, Wei Zheng, Christian C Abnet, Demetrius Albanes, Gabriella Andreotti, Lauren Brais, H Bas Bueno-de-Mesquita, Daniela Basso, Sonja I Berndt, Marie-Christine Boutron-Ruault, Maarten F Bijlsma, Hermann Brenner, Laurie Burdette, Daniele Campa, Neil E Caporaso, Gabriele Capurso, Giulia Martina Cavestro, Michelle Cotterchio, Eithne Costello, Joanne Elena, Ugo Boggi, J Michael Gaziano, Maria Gazouli, Edward L Giovannucci, Michael Goggins, Myron Gross, Christopher A Haiman, Manal Hassan, Kathy J Helzlsouer, Nan Hu, David J Hunter, Elzbieta Iskierka-Jazdzewska, Mazda Jenab, Rudolf Kaaks, Timothy J Key, Kay-Tee Khaw, Eric A Klein, Manolis Kogevinas, Vittorio Krogh, Juozas Kupcinskas, Robert C Kurtz, Maria T Landi, Stefano Landi, Loic Le Marchand, Andrea Mambrini, Satu Mannisto, Roger L Milne, Rachel E Neale, Ann L Oberg, Salvatore Panico, Alpa V Patel, Petra H M Peeters, Ulrike Peters, Raffaele Pezzilli, Miquel Porta, Mark Purdue, J Ramón Quiros, Elio Riboli, Nathaniel Rothman, Aldo Scarpa, Ghislaine Scelo, Xiao-Ou Shu, Debra T Silverman, Pavel Soucek, Oliver Strobel, Malin Sund, Ewa Małecka-Panas, Philip R Taylor, Francesca Tavano, Ruth C Travis, Mark Thornquist, Anne Tjønneland, Geoffrey S Tobias, Dimitrios Trichopoulos, Yogesh Vashist, Pavel Vodicka, Jean Wactawski-Wende, Nicolas Wentzensen, Herbert Yu, Kai Yu, Anne Zeleniuch-Jacquotte, Charles Kooperberg, Harvey A Risch, Eric J Jacobs, Donghui Li, Charles Fuchs, Robert Hoover, Patricia Hartge, Stephen J Chanock, Gloria M Petersen, Rachael S Stolzenberg-Solomon, Brian M Wolpin, Peter Kraft, Alison P Klein, Federico Canzian, Laufey T Amundadottir
Genome-wide association studies (GWAS) have identified common pancreatic cancer susceptibility variants at 13 chromosomal loci in individuals of European descent. To identify new susceptibility variants, we performed imputation based on 1000 Genomes (1000G) Project data and association analysis using 5,107 case and 8,845 control subjects from 27 cohort and case-control studies that participated in the PanScan I-III GWAS. This analysis, in combination with a two-staged replication in an additional 6,076 case and 7,555 control subjects from the PANcreatic Disease ReseArch (PANDoRA) and Pancreatic Cancer Case-Control (PanC4) Consortia uncovered 3 new pancreatic cancer risk signals marked by single nucleotide polymorphisms (SNPs) rs2816938 at chromosome 1q32...
October 11, 2016: Oncotarget
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JOURNAL ARTICLE
Yeting Du, Monica Ter-Minassian, Lauren Brais, Nichole Brooks, Amanda Waldron, Jennifer A Chan, Xihong Lin, Peter Kraft, David C Christiani, Matthew H Kulke
The etiology of neuroendocrine tumors remains poorly defined. Although neuroendocrine tumors are in some cases associated with inherited genetic syndromes, such syndromes are rare. The majority of neuroendocrine tumors are thought to be sporadic. We performed a genome-wide association study (GWAS) to identify potential genetic risk factors for sporadic neuroendocrine tumors. Using germline DNA from blood specimens, we genotyped 909,622 SNPs using the Affymetrix 6.0 GeneChip, in a cohort comprising 832 neuroendocrine tumor cases from Dana-Farber Cancer Institute and Massachusetts General Hospital and 4542 controls from the Harvard School of Public Health...
August 2016: Endocrine-related Cancer
#46
JOURNAL ARTICLE
Mizuki Nishino, Lauren K Brais, Nichole V Brooks, Hiroto Hatabu, Matthew H Kulke, Nikhil H Ramaiya
PURPOSE: The purpose of this study was to investigate the incidence of drug-related pneumonitis during mammalian target of rapamycin (mTOR) inhibitor therapy in patients with neuroendocrine tumours (NET) and characterise radiographic patterns of pneumonitis. METHODS: Sixty-six patients (39 males, 27 females, age: 22-79 years) with advanced NET treated with mTOR inhibitor, everolimus, were retrospectively studied. Chest computed tomography scans during therapy were reviewed for abnormalities suspicious for drug-related pneumonitis by an independent review of two radiologists...
January 2016: European Journal of Cancer
#47
JOURNAL ARTICLE
Anne Elias, Nikolaos A Chatzizacharias, Athanasios Xanthis, Pippa Corrie, Susan Davies, Rebecca J Brais, Neville V Jamieson, Raaj K Praseedom, Emmanuel Huguet, Simon J F Harper, Asif Jah
Pancreatic cancer is known for its typically late presentation and poor survival rates, with overall 5-year survival of less than 5%. The role of chemotherapy alone or with radiotherapy in the management of locally advanced tumors continues to be an area of debate.We report a case of locally advanced, pancreatic adenosquamous carcinoma that was initially deemed unresectable intraoperatively. Nonetheless, the tumor was resected after radiological response to gemcitabine-capecitabine chemoradiotherapy regimen similar to the Selective Chemoradiation in Advanced LOcalised Pancreatic cancer trial...
February 2015: Medicine (Baltimore)
#48
JOURNAL ARTICLE
Anna Schnell, Sylvie Chappuis, Isabelle Schmutz, Emanuele Brai, Jürgen A Ripperger, Olivier Schaad, Hans Welzl, Patrick Descombes, Lavinia Alberi, Urs Albrecht
The function of the nuclear receptor Rev-erbα (Nr1d1) in the brain is, apart from its role in the circadian clock mechanism, unknown. Therefore, we compared gene expression profiles in the brain between wild-type and Rev-erbα knock-out (KO) animals. We identified fatty acid binding protein 7 (Fabp7, Blbp) as a direct target of repression by REV-ERBα. Loss of Rev-erbα manifested in memory and mood related behavioral phenotypes and led to overexpression of Fabp7 in various brain areas including the subgranular zone (SGZ) of the hippocampus, where neuronal progenitor cells (NPCs) can initiate adult neurogenesis...
2014: PloS One
#49
JOURNAL ARTICLE
Joshua M Francis, Adam Kiezun, Alex H Ramos, Stefano Serra, Chandra Sekhar Pedamallu, Zhi Rong Qian, Michaela S Banck, Rahul Kanwar, Amit A Kulkarni, Anna Karpathakis, Veronica Manzo, Tanupriya Contractor, Juliet Philips, Elizabeth Nickerson, Nam Pho, Susanne M Hooshmand, Lauren K Brais, Michael S Lawrence, Trevor Pugh, Aaron McKenna, Andrey Sivachenko, Kristian Cibulskis, Scott L Carter, Akinyemi I Ojesina, Samuel Freeman, Robert T Jones, Douglas Voet, Gordon Saksena, Daniel Auclair, Robert Onofrio, Erica Shefler, Carrie Sougnez, Jonna Grimsby, Lisa Green, Niall Lennon, Tim Meyer, Martyn Caplin, Daniel C Chung, Andreas S Beutler, Shuji Ogino, Christina Thirlwell, Ramesh Shivdasani, Sylvia L Asa, Chris R Harris, Gad Getz, Matthew Kulke, Matthew Meyerson
The diagnosed incidence of small intestine neuroendocrine tumors (SI-NETs) is increasing, and the underlying genomic mechanisms have not yet been defined. Using exome- and genome-sequence analysis of SI-NETs, we identified recurrent somatic mutations and deletions in CDKN1B, the cyclin-dependent kinase inhibitor gene, which encodes p27. We observed frameshift mutations of CDKN1B in 14 of 180 SI-NETs, and we detected hemizygous deletions encompassing CDKN1B in 7 out of 50 SI-NETs, nominating p27 as a tumor suppressor and implicating cell cycle dysregulation in the etiology of SI-NETs...
December 2013: Nature Genetics
#50
JOURNAL ARTICLE
Zhi Rong Qian, Monica Ter-Minassian, Jennifer A Chan, Yu Imamura, Susanne M Hooshmand, Aya Kuchiba, Teppei Morikawa, Lauren K Brais, Anastassia Daskalova, Rachel Heafield, Xihong Lin, David C Christiani, Charles S Fuchs, Shuji Ogino, Matthew H Kulke
PURPOSE: Clinical studies have implicated the mechanistic target of rapamycin (serine/threonine kinase; MTOR) pathway in the regulation of neuroendocrine tumor (NET) growth. We explored whether expression of MTOR pathway components has prognostic significance in NET patients. PATIENTS AND METHODS: We evaluated immunohistochemical expression of MTOR and phospho (p) -MTOR; its downstream targets RPS6KB1, RPS6, and EIF4EBP1; and its upstream regulators, in a cohort of 195 archival neuroendocrine tumors...
September 20, 2013: Journal of Clinical Oncology
#51
JOURNAL ARTICLE
Monica Ter-Minassian, Jennifer A Chan, Susanne M Hooshmand, Lauren K Brais, Anastassia Daskalova, Rachel Heafield, Laurie Buchanan, Zhi Rong Qian, Charles S Fuchs, Xihong Lin, David C Christiani, Matthew H Kulke
The rarity of neuroendocrine tumors (NET) has contributed to a paucity of large epidemiologic studies of patients with this condition. We characterized presenting symptoms and clinical outcomes in a prospective database of over 900 patients with NET. We used data from patient questionnaires and the medical record to characterize presenting symptoms, disease-free survival (DFS), and overall survival (OS). The majority of patients in this database had gastroenteropancreatic NET. The median duration of patient-reported symptoms before diagnosis was 3...
April 2013: Endocrine-related Cancer
#52
COMPARATIVE STUDY
Rebecca J Brais, Susan E Davies, Maria O'Donovan, Ben W Simpson, Natalie Cook, Walter C Darbonne, Sian Chilcott, Martijn P Lolkema, Albrecht Neesse, Michelle Lockley, Pippa G Corrie, Duncan I Jodrell, Raaj K Praseedom, Emmanuel L Huguet, Asif Jah, Neville V Jamieson, Frederic J de Sauvage, David A Tuveson, Nicholas R Carroll
OBJECTIVE: Current practice to diagnose pancreatic cancer is accomplished by endoscopic ultrasound guided fine needle aspiration (EUS-FNA) using a cytological approach. This method is time consuming and often fails to provide suitable specimens for modern molecular analyses. Here, we compare the cytological approach with direct formalin fixation of pancreatic EUS-FNA micro-cores and evaluate the potential to perform molecular biomarker analysis on these specimen. METHODS: 130 specimens obtained by EUS-FNA with a 22G needle were processed by the standard cytological approach and compared to a separate cohort of 130 specimens that were immediately formalin fixed to preserve micro-cores of tissue prior to routine histological processing...
January 2012: Pancreatology: Official Journal of the International Association of Pancreatology (IAP) ... [et Al.]
#53
JOURNAL ARTICLE
Jason M Ali, Luca Bonomo, Rebecca Brais, William J H Griffiths, David J Lomas, Emmanuel L Huguet, Raaj K Praseedom, Neville V Jamieson, Asif Jah
BACKGROUND: Liver transplantation in the presence of cholangiocarcinoma (CCA) generally carries a poor prognosis. However, the outcome of patients found to have incidental CCA (iCCA) on explanted liver histology is less clear. We have evaluated the outcomes of iCCA in our liver transplant population. METHODS: A retrospective search was made of the transplantation and histopathology databases for patients fulfilling our definition for iCCA. All records, including archived histopathologic slides were retrieved and analyzed...
June 27, 2011: Transplantation
#54
JOURNAL ARTICLE
Dimitrios Chorianopoulos, Konstantinos Samitas, Stylianos Vittorakis, Vasiliki Kiriazi, Dimitra Rondoyianni, Georgios Tsaousis, Athanasios Skoutelis
A 51-year-old previously healthy man, an ex-smoker, was admitted to the authors' medical department with a 3-month history of dry cough; intermittent fever; painless, ulcerated cutaneous lesions over the trunk and limbs (Figure 1); and progressive weight loss. He was of Greek descent. His medical history was remarkable for nasal polyps, which were surgically removed 15 years earlier. Initially, he had been treated with antibiotics, without improvement. Several days before admission, chest radiography revealed pulmonary infiltrates in the left lower lobe...
January 2010: Skinmed
#55
COMPARATIVE STUDY
Pierre Lao-Sirieix, Rebecca Brais, Laurence Lovat, Nicholas Coleman, Rebecca C Fitzgerald
Barrett's esophagus (BE) epithelium is the precursor lesion for esophageal adenocarcinoma. Cell cycle proteins have been advocated as biomarkers to predict the malignant potential in BE. However, whether disruption of the cell cycle plays a causal role in Barrett's carcinogenesis is not clear. Specimens from the Barrett's dysplasia-carcinoma sequence were immunostained for cell cycle phase markers (cyclin D1 for G1; cyclin A for S, G2, and M; cytoplasmic cyclin B1 for G2; and phosphorylated histone 3 for M phase) and expressed as a proportion of proliferating cells...
November 2004: Neoplasia: An International Journal for Oncology Research
#56
JOURNAL ARTICLE
M Brai, A G Osler
No abstract text is available yet for this article.
November 1973: Journal of Immunology
#57
JOURNAL ARTICLE
J Heppell, M De Zubiria, M F Brais, M A Durh, S Carioto, Y Boivin, C Potvin
This study was undertaken to determine if the construction of an ileal reservoir induces mucosal changes that can potentiate the effect of a chemical carcinogen (1,2-dimethylhydrazine) on ileal mucosa. Animals were divided into three groups: 1) sham operation (n = 19), 2) total colectomy with ileorectal anastomosis (n = 20), 3) total colectomy with an ileal reservoir made of terminal ileum sutured to the rectum (n = 20). An adaptation period of 12 weeks was allowed to promote fecal stasis and the histologic changes before exposure to weekly subcutaneous injections of DMH (25 mg/kg) for 16 weeks...
January 1990: Diseases of the Colon and Rectum
#58
JOURNAL ARTICLE
M Brai, L Bonasera, G Tolone
Methylcholanthrene, in amount sufficient to induce tumors in 100% of treated animals failed to influence primary and secondary phases of antibody synthesis in mice immunized with sheep erythrocytes and human serum albumin. The early immune response in tumor bearing mice was also indistinguischable from that of normal animals, despite the presence of marked splenomegaly in the former group.
January 1975: Giornale di Batteriologia, Virologia Ed Immunologia
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