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https://www.readbyqxmd.com/read/29045506/clinical-and-molecular-characterization-of-patients-with-cancers-of-unknown-primary-in-the-modern-era
#1
A M Varghese, A Arora, M Capanu, N Camacho, H H Won, A Zehir, J Gao, D Chakravarty, N Schultz, D S Klimstra, M Ladanyi, D M Hyman, D B Solit, M F Berger, L B Saltz
Background: On the basis of historical data, patients with cancers of unknown primary (CUP) are generally assumed to have a dismal prognosis with overall survival of less than one year. Treatment is typically cytotoxic chemotherapy guided by histologic features and the pattern of metastatic spread. The purpose of this study was to provide a clinical and pathologic description of patients with CUP in the modern era, to define the frequency of clinically actionable molecular alterations in this population, to determine how molecular testing can alter therapeutic decisions, and to investigate novel uses of next generation sequencing in the evaluation and treatment of patients with CUP...
September 26, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/29044913/assessment-of-cytologic-differentiation-in-high-grade-pancreatic-neuroendocrine-neoplasms-a-multi-institutional-study
#2
Carlie S Sigel, Vitor Werneck Krauss Silva, Michelle D Reid, David Chhieng, Olca Basturk, Keith M Sigel, Tanisha D Daniel, David S Klimstra, Laura H Tang
BACKGROUND: Well-differentiated (WD) and poorly differentiated (PD) pancreatic neuroendocrine neoplasms are biologically distinct entities with different therapies and prognoses. WD neoplasms with elevated proliferation (Ki-67 > 20%) have been shown to have an overlapping histology with PD neuroendocrine carcinomas. This study compared expert cytomorphologic assessments of differentiation in pancreatic neuroendocrine neoplasms in a multi-institutional study. METHODS: Fine-needle aspiration specimens from pancreatic neuroendocrine neoplasms (grade 2 [G2] and grade 3 [G3] according to the 2017 World Health Organization classification; n = 72) were diagnosed independently by 3 cytopathologists as WD or PD (poorly differentiated large cell type [PD-L] or poorly differentiated small cell type [PD-S]) purely on the basis of cytomorphology...
October 17, 2017: Cancer
https://www.readbyqxmd.com/read/28884748/a-fish-assay-efficiently-screens-for-braf-gene-rearrangements-in-pancreatic-acinar-type-neoplasms
#3
Lu Wang, Olca Basturk, Jiajing Wang, Ryma Benayed, Sumit Middha, Ahmet Zehir, Irina Linkov, Mamta Rao, Ruth Aryeequaye, Long Cao, Juliann Chmielecki, Jeffrey Ross, Philip J Stephens, Volkan Adsay, Gokce Askan, Serdar Balci, David S Klimstra
Approximately 1-2% of pancreatic neoplasms are acinar cell carcinomas. Recently, BRAF gene rearrangements were identified in over 20% of acinar-type neoplasms, which included both pure acinar cell carcinomas and mixed carcinomas with acinar differentiation, using next-generation sequencing-based platforms, providing a potential therapeutic target for patients with these neoplasms. Thus, it is clinically important to develop a rapid, cost- and material-efficient assay to screen for BRAF gene fusions in pancreatic acinar-type neoplasms...
September 8, 2017: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/28873162/mutation-detection-in-patients-with-advanced-cancer-by-universal-sequencing-of-cancer-related-genes-in-tumor-and-normal-dna-vs-guideline-based-germline-testing
#4
Diana Mandelker, Liying Zhang, Yelena Kemel, Zsofia K Stadler, Vijai Joseph, Ahmet Zehir, Nisha Pradhan, Angela Arnold, Michael F Walsh, Yirong Li, Anoop R Balakrishnan, Aijazuddin Syed, Meera Prasad, Khedoudja Nafa, Maria I Carlo, Karen A Cadoo, Meg Sheehan, Megan H Fleischut, Erin Salo-Mullen, Magan Trottier, Steven M Lipkin, Anne Lincoln, Semanti Mukherjee, Vignesh Ravichandran, Roy Cambria, Jesse Galle, Wassim Abida, Marcia E Arcila, Ryma Benayed, Ronak Shah, Kenneth Yu, Dean F Bajorin, Jonathan A Coleman, Steven D Leach, Maeve A Lowery, Julio Garcia-Aguilar, Philip W Kantoff, Charles L Sawyers, Maura N Dickler, Leonard Saltz, Robert J Motzer, Eileen M O'Reilly, Howard I Scher, Jose Baselga, David S Klimstra, David B Solit, David M Hyman, Michael F Berger, Marc Ladanyi, Mark E Robson, Kenneth Offit
Importance: Guidelines for cancer genetic testing based on family history may miss clinically actionable genetic changes with established implications for cancer screening or prevention. Objective: To determine the proportion and potential clinical implications of inherited variants detected using simultaneous sequencing of the tumor and normal tissue ("tumor-normal sequencing") compared with genetic test results based on current guidelines. Design, Setting, and Participants: From January 2014 until May 2016 at Memorial Sloan Kettering Cancer Center, 10 336 patients consented to tumor DNA sequencing...
September 5, 2017: JAMA: the Journal of the American Medical Association
https://www.readbyqxmd.com/read/28857328/different-aspects-of-emotional-intelligence-of-borderline-personality-disorder
#5
Mathell Peter, Arnoud R Arntz, Theo Klimstra, Ad J J M Vingerhoets
OBJECTIVES: The present study investigated deficiencies in different components of emotional intelligence in borderline personality disorder (BPD). METHOD: The Mayer-Salovey-Caruso Emotional Intelligence Test (MSCEIT) and the Emotional Quotient Inventory (EQ-i) were used to assess EI dimensions. BPD patients (N = 85; 69 women; M = 33.6 years) were compared with Cluster C personality disorder (PD) patients (N = 39; 23 women; M = 36.6 years) and nonpatients (N = 69; 44 women; M = 35...
August 30, 2017: Clinical Psychology & Psychotherapy
https://www.readbyqxmd.com/read/28819720/immunohistochemical-null-phenotype-for-mismatch-repair-proteins-in-colonic-carcinoma-associated-with-concurrent-mlh1-hypermethylation-and-msh2-somatic-mutations
#6
Tao Wang, Zsofia K Stadler, Liying Zhang, Martin R Weiser, Olca Basturk, Jaclyn F Hechtman, Efsevia Vakiani, Lenard B Saltz, David S Klimstra, Jinru Shia
Microsatellite instability, a well-established driver pathway in colorectal carcinogenesis, can develop in both sporadic and hereditary conditions via different molecular alterations in the DNA mismatch repair (MMR) genes. MMR protein immunohistochemistry (IHC) is currently widely used for the detection of MMR deficiency in solid tumors. The IHC test, however, can show varied staining patterns, posing challenges in the interpretation of the staining results in some cases. Here we report a case of an 80-year-old female with a colonic adenocarcinoma that exhibited an unusual "null" IHC staining pattern with complete loss of all four MMR proteins (MLH1, MSH2, MSH6, and PMS2)...
August 17, 2017: Familial Cancer
https://www.readbyqxmd.com/read/28777785/erratum-mutational-landscape-of-metastatic-cancer-revealed-from-prospective-clinical-sequencing-of-10-000-patients
#7
Ahmet Zehir, Ryma Benayed, Ronak H Shah, Aijazuddin Syed, Sumit Middha, Hyunjae R Kim, Preethi Srinivasan, Jianjiong Gao, Debyani Chakravarty, Sean M Devlin, Matthew D Hellmann, David A Barron, Alison M Schram, Meera Hameed, Snjezana Dogan, Dara S Ross, Jaclyn F Hechtman, Deborah F DeLair, JinJuan Yao, Diana L Mandelker, Donavan T Cheng, Raghu Chandramohan, Abhinita S Mohanty, Ryan N Ptashkin, Gowtham Jayakumaran, Meera Prasad, Mustafa H Syed, Anoop Balakrishnan Rema, Zhen Y Liu, Khedoudja Nafa, Laetitia Borsu, Justyna Sadowska, Jacklyn Casanova, Ruben Bacares, Iwona J Kiecka, Anna Razumova, Julie B Son, Lisa Stewart, Tessara Baldi, Kerry A Mullaney, Hikmat Al-Ahmadie, Efsevia Vakiani, Adam A Abeshouse, Alexander V Penson, Philip Jonsson, Niedzica Camacho, Matthew T Chang, Helen H Won, Benjamin E Gross, Ritika Kundra, Zachary J Heins, Hsiao-Wei Chen, Sarah Phillips, Hongxin Zhang, Jiaojiao Wang, Angelica Ochoa, Jonathan Wills, Michael Eubank, Stacy B Thomas, Stuart M Gardos, Dalicia N Reales, Jesse Galle, Robert Durany, Roy Cambria, Wassim Abida, Andrea Cercek, Darren R Feldman, Mrinal M Gounder, A Ari Hakimi, James J Harding, Gopa Iyer, Yelena Y Janjigian, Emmet J Jordan, Ciara M Kelly, Maeve A Lowery, Luc G T Morris, Antonio M Omuro, Nitya Raj, Pedram Razavi, Alexander N Shoushtari, Neerav Shukla, Tara E Soumerai, Anna M Varghese, Rona Yaeger, Jonathan Coleman, Bernard Bochner, Gregory J Riely, Leonard B Saltz, Howard I Scher, Paul J Sabbatini, Mark E Robson, David S Klimstra, Barry S Taylor, Jose Baselga, Nikolaus Schultz, David M Hyman, Maria E Arcila, David B Solit, Marc Ladanyi, Michael F Berger
No abstract text is available yet for this article.
August 4, 2017: Nature Medicine
https://www.readbyqxmd.com/read/28776573/pancreatic-intraductal-tubulopapillary-neoplasm-is-genetically-distinct-from-intraductal-papillary-mucinous-neoplasm-and-ductal-adenocarcinoma
#8
Olca Basturk, Michael F Berger, Hiroshi Yamaguchi, Volkan Adsay, Gokce Askan, Umesh K Bhanot, Ahmet Zehir, Fatima Carneiro, Seung-Mo Hong, Giuseppe Zamboni, Esra Dikoglu, Vaidehi Jobanputra, Kazimierz O Wrzeszczynski, Serdar Balci, Peter Allen, Naoki Ikari, Shoko Takeuchi, Hiroyuki Akagawa, Atsushi Kanno, Tooru Shimosegawa, Takanori Morikawa, Fuyuhiko Motoi, Michiaki Unno, Ryota Higuchi, Masakazu Yamamoto, Kyoko Shimizu, Toru Furukawa, David S Klimstra
Intraductal tubulopapillary neoplasm is a relatively recently described member of the pancreatic intraductal neoplasm family. The more common member of this family, intraductal papillary mucinous neoplasm, often carries genetic alterations typical of pancreatic infiltrating ductal adenocarcinoma (KRAS, TP53, and CDKN2A) but additionally has mutations in GNAS and RNF43 genes. However, the genetic characteristics of intraductal tubulopapillary neoplasm have not been well characterized. Twenty-two intraductal tubulopapillary neoplasms were analyzed by either targeted next-generation sequencing, which enabled the identification of sequence mutations, copy number alterations, and selected structural rearrangements involving all targeted (≥300) genes, or whole-exome sequencing...
August 4, 2017: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/28754816/real-time-genomic-profiling-of-pancreatic-ductal-adenocarcinoma-potential-actionability-and-correlation-with-clinical-phenotype
#9
Maeve A Lowery, Emmet J Jordan, Olca Basturk, Ryan N Ptashkin, Ahmet Zehir, Michael F Berger, Tanisha Leach, Brian Herbst, Gokce Askan, Hannah Maynard, Danielle Glassman, Christina Covington, Nikolaus Schultz, Ghassan K Abou-Alfa, James J Harding, David S Klimstra, Jaclyn F Hechtman, David M Hyman, Peter J Allen, William R Jarnagin, Vinod P Balachandran, Anna M Varghese, Mark A Schattner, Kenneth H Yu, Leonard B Saltz, David B Solit, Christine A Iacobuzio-Donahue, Steven D Leach, Eileen M O'Reilly
Purpose: Molecular profiling in cancer has identified potential actionable drug targets that have prompted attempts to discover clinically validated biomarkers to guide therapeutic decision-making and enrollment to clinical trials. We evaluated whether comprehensive genetic analysis of patients with pancreatic adenocarcinoma is feasible within a clinically relevant timeframe and whether such analyses provide predictive and/or prognostic information along with identification of potential targets for therapy...
October 15, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28719467/pan-trk-immunohistochemistry-is-an-efficient-and-reliable-screen-for-the-detection-of-ntrk-fusions
#10
Jaclyn F Hechtman, Ryma Benayed, David M Hyman, Alexander Drilon, Ahmet Zehir, Denise Frosina, Maria E Arcila, Snjezana Dogan, David S Klimstra, Marc Ladanyi, Achim A Jungbluth
Activating neurotrophic tyrosine receptor kinase (NTRK) fusions, typically detected using nucleic-acid based assays, are highly targetable and define certain tumors. Here, we explore the utility of pan-TRK immunohistochemistry (IHC) to detect NTRK fusions. NTRK rearrangements were detected prospectively using MSK-IMPACT, a DNA-based next-generation sequencing assay. Transcription of novel NTRK rearrangements into potentially functional fusion transcripts was assessed via Archer Dx fusion assay. Pan-Trk IHC testing with mAb EPR17341 was performed on all NTRK rearranged cases and 20 cases negative for NTRK fusions on Archer...
November 2017: American Journal of Surgical Pathology
https://www.readbyqxmd.com/read/28686653/ribbon-scanning-confocal-for-high-speed-high-resolution-volume-imaging-of-brain
#11
Alan M Watson, Annika H Rose, Gregory A Gibson, Christina L Gardner, Chengqun Sun, Douglas S Reed, L K Metthew Lam, Claudette M St Croix, Peter L Strick, William B Klimstra, Simon C Watkins
Whole-brain imaging is becoming a fundamental means of experimental insight; however, achieving subcellular resolution imagery in a reasonable time window has not been possible. We describe the first application of multicolor ribbon scanning confocal methods to collect high-resolution volume images of chemically cleared brains. We demonstrate that ribbon scanning collects images over ten times faster than conventional high speed confocal systems but with equivalent spectral and spatial resolution. Further, using this technology, we reconstruct large volumes of mouse brain infected with encephalitic alphaviruses and demonstrate that regions of the brain with abundant viral replication were inaccessible to vascular perfusion...
2017: PloS One
https://www.readbyqxmd.com/read/28650392/o6-methylguanine-dna-methyltransferase-status-does-not-predict-response-or-resistance-to-alkylating-agents-in-well-differentiated-pancreatic-neuroendocrine-tumors
#12
Nitya Raj, David S Klimstra, Natally Horvat, Liying Zhang, Joanne F Chou, Marinela Capanu, Olca Basturk, Richard Kinh Gian Do, Peter J Allen, Diane Reidy-Lagunes
OBJECTIVES: Alkylating agents have activity in well-differentiated pancreatic neuroendocrine tumors (WD panNETs). In glioblastoma multiforme, decreased activity of O-methylguanine DNA methyltransferase (MGMT) predicts response; in panNETs, MGMT relevance is unknown. METHODS: We identified patients with WD panNETs treated with alkylating agents, determined best overall response by Response Evaluation Criteria In Solid Tumors (RECIST) 1.1, and performed MGMT activity testing...
June 22, 2017: Pancreas
https://www.readbyqxmd.com/read/28609363/o6-methylguanine-dna-methyltransferase-status-does-not-predict-response-or-resistance-to-alkylating-agents-in-well-differentiated-pancreatic-neuroendocrine-tumors
#13
Nitya Raj, David S Klimstra, Natally Horvat, Liying Zhang, Joanne F Chou, Marinela Capanu, Olca Basturk, Richard Kinh Gian Do, Peter J Allen, Diane Reidy-Lagunes
OBJECTIVES: Alkylating agents have activity in well-differentiated pancreatic neuroendocrine tumors (WD panNETs). In glioblastoma multiforme, decreased activity of O-methylguanine DNA methyltransferase (MGMT) predicts response; in panNETs, MGMT relevance is unknown. METHODS: We identified patients with WD panNETs treated with alkylating agents, determined best overall response by Response Evaluation Criteria In Solid Tumors (RECIST) 1.1, and performed MGMT activity testing...
July 2017: Pancreas
https://www.readbyqxmd.com/read/28581654/daily-dynamics-of-adolescent-mood-and-identity
#14
Theo A Klimstra, Peter Kuppens, Koen Luyckx, Susan Branje, William W Hale, Annerieke Oosterwegel, Hans M Koot, Wim H J Meeus
Important linkages between daily mood and identity formation have been theorized, but have not been empirically tested as of yet. This study provided a first examination of these linkages within individuals (N = 392; 55.1% boys; Mage at T1 = 13.24, SD = 0.44) across 15 series of 5 days distributed over 5 years. Results revealed negative within-time associations of educational and relational commitment with negative mood. Negative mood was positively associated with educational in-depth exploration and educational and interpersonal reconsideration...
September 2016: Journal of Research on Adolescence: the Official Journal of the Society for Research on Adolescence
https://www.readbyqxmd.com/read/28572718/longitudinal-associations-between-parental-bonding-parenting-stress-and-executive-functioning-in-toddlerhood
#15
Evi S A de Cock, Jens Henrichs, Theo A Klimstra, A Janneke B M Maas, Charlotte M J M Vreeswijk, Wim H J Meeus, Hedwig J A van Bakel
Early executive functioning is an important predictor for future development of children's cognitive skills and behavioral outcomes. Parenting behavior has proven to be a key environmental determinant of child executive functioning. However, the association of parental affect and cognitions directed to the child with child executive functioning has been understudied. Therefore, in the present study we examine the associations between parental bonding (i.e., the affective tie from parent to child), parenting stress, and child executive functioning...
2017: Journal of Child and Family Studies
https://www.readbyqxmd.com/read/28565933/comparing-executive-function-evoked-hemodynamic-response-and-gait-as-predictors-of-variations-in-mobility-for-older-adults
#16
Drew W R Halliday, Sandra R Hundza, Mauricio A Garcia-Barrera, Marc Klimstra, Drew Commandeur, Timothy V Lukyn, Robert S Stawski, Stuart W S MacDonald
OBJECTIVE: Falls represent a major concern for older adults and may serve as clinically salient index events for those presenting in the prodromal stages of mild cognitive impairment. Declines in executive function performance and in gait consistency have shown promise in predicting fall risk; however, associated neurophysiological underpinnings have received less attention. In this study, we used a multimodal approach to assess fall risk in a group of older adults with and without a previous fall history...
May 31, 2017: Journal of Clinical and Experimental Neuropsychology
https://www.readbyqxmd.com/read/28498280/immunohistochemical-characterization-of-the-origins-of-metastatic-well-differentiated-neuroendocrine-tumors-to-the-liver
#17
Zhaohai Yang, David S Klimstra, Ralph H Hruban, Laura H Tang
Metastatic neoplasms of unknown primary site pose a major challenge to patient management. As targeted therapies are now being tailored to neuroendocrine tumors (NETs) of different primary sites, identifying the origin of metastatic NETs has become increasingly important. Compared with more extensive efforts on metastatic adenocarcinomas of unknown primary, the literature on metastatic NETs (often to the liver) is relatively sparse and most studies are based on primary tumors. We sought to study metastatic well-differentiated NETs to the liver to identify markers that predict the site of origin...
July 2017: American Journal of Surgical Pathology
https://www.readbyqxmd.com/read/28487016/the-expression-level-of-c19mc-mirnas-in-early-pregnancy-and-in-response-to-viral-infection
#18
Tina M F Dumont, Jean-Francois Mouillet, Avaraham Bayer, Christina L Gardner, William B Klimstra, Dana G Wolf, Simcha Yagel, Fabiola Balmir, Anna Binstock, Joseph S Sanfilippo, Carolyn B Coyne, Jacob C Larkin, Yoel Sadovsky
INTRODUCTION: We have previously shown that miRNAs produced from the Chromosome 19 MiRNA Cluster (C19MC), which are expressed almost exclusively in primate trophoblasts and are released into the maternal circulation, reduce viral replication in non-placental cells and can modulate migratory behavior of extravillous trophoblast. We sought to define the expression pattern of C19MC miRNA in early pregnancy and in response to viral infection in vitro and in vivo. METHODS: We prospectively followed women undergoing in vitro fertilization (IVF) and determined their blood level of C19MC miRNA using RT-qPCR...
May 2017: Placenta
https://www.readbyqxmd.com/read/28486549/genome-and-transcriptome-profiling-of-fibrolamellar-hepatocellular-carcinoma-demonstrates-p53-and-igf2bp1-dysregulation
#19
Eric C Sorenson, Raya Khanin, Zubin M Bamboat, Michael J Cavnar, Teresa S Kim, Eran Sadot, Shan Zeng, Jonathan B Greer, Adrian M Seifert, Noah A Cohen, Megan H Crawley, Benjamin L Green, David S Klimstra, Ronald P DeMatteo
Fibrolamellar hepatocellular carcinoma (FL-HCC) is a rare variant of HCC that most frequently affects young adults. Because of its rarity and an absence of preclinical models, our understanding of FL-HCC is limited. Our objective was to analyze chromosomal alterations and dysregulated gene expression in tumor specimens collected at a single center during two decades of experience with FL-HCC. We analyzed 38 specimens from 26 patients by array comparative genomic hybridiziation (aCGH) and 35 specimens from 15 patients by transcriptome sequencing (RNA-seq)...
2017: PloS One
https://www.readbyqxmd.com/read/28485185/exploring-the-ecological-validity-and-variability-of-a-10-min-bout-of-wheeling
#20
Megan K MacGillivray, Tania Lam, Marc Klimstra, E Paul Zehr, Bonita J Sawatzky
PURPOSE: To determine the ecological validity of using able-bodied participants to perform a 10-min wheeling trial by (1) evaluating changes in biomechanics over the trial in manual wheelchair users and able-bodied participants naïve to wheeling and (2) describing differences in changes and variability between groups. MATERIALS AND METHODS: Manual wheelchair users (n = 7, 2-27 years' experience) and able-bodied participants (n = 11) wheeled for 10 min...
May 9, 2017: Disability and Rehabilitation. Assistive Technology
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