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https://www.readbyqxmd.com/read/28295729/targeting-of-b-cell-receptor-signalling-in-b-cell-malignancies
#1
M Jerkeman, M Hallek, M Dreyling, C Thieblemont, E Kimby, L Staudt
Pharmacological agents that inhibit enzymes of the B-cell receptor (BCR) pathway are of increasing importance in the treatment of B-cell malignancies. These include inhibitors of Bruton tyrosine kinase (BTK), phosphatidylinositol 3-kinase (PI3K), splenic tyrosine kinase and protein kinase Cβ. Two agents are already approved in the USA and Europe: ibrutinib, a BTK inhibitor, for the treatment of chronic lymphatic leukaemia (CLL), mantle cell lymphoma (MCL) and Waldenström's macroglobulinemia; and idelalisib, a PI3Kδ inhibitor, for the treatment of CLL and follicular lymphoma...
March 14, 2017: Journal of Internal Medicine
https://www.readbyqxmd.com/read/28214419/recommendations-for-gonadotoxicity-surveillance-in-male-childhood-adolescent-and-young-adult-cancer-survivors-a-report-from-the-international-late-effects-of-childhood-cancer-guideline-harmonization-group-in-collaboration-with-the-pancaresurfup-consortium
#2
REVIEW
Roderick Skinner, Renee L Mulder, Leontien C Kremer, Melissa M Hudson, Louis S Constine, Edit Bardi, Annelies Boekhout, Anja Borgmann-Staudt, Morven C Brown, Richard Cohn, Uta Dirksen, Alexsander Giwercman, Hiroyuki Ishiguro, Kirsi Jahnukainen, Lisa B Kenney, Jacqueline J Loonen, Lilian Meacham, Sebastian Neggers, Stephen Nussey, Cecilia Petersen, Margarett Shnorhavorian, Marry M van den Heuvel-Eibrink, Hanneke M van Santen, William H B Wallace, Daniel M Green
Treatment with chemotherapy, radiotherapy, or surgery that involves reproductive organs can cause impaired spermatogenesis, testosterone deficiency, and physical sexual dysfunction in male pubertal, adolescent, and young adult cancer survivors. Guidelines for surveillance and management of potential adverse effects could improve cancer survivors' health and quality of life. Surveillance recommendations vary considerably, causing uncertainty about optimum screening practices. This clinical practice guideline recommended by the International Late Effects of Childhood Cancer Guideline Harmonization Group in collaboration with the PanCareSurFup Consortium, developed using evidence-based methodology, critically synthesises surveillance recommendations for gonadotoxicity in male childhood, adolescent, and young adult (CAYA) cancer survivors...
February 2017: Lancet Oncology
https://www.readbyqxmd.com/read/27977460/perioperative-outcomes-and-management-in-pediatric-complex-cranial-vault-reconstruction-a-multicenter-study-from-the-pediatric-craniofacial-collaborative-group
#3
Paul A Stricker, Susan M Goobie, Franklyn P Cladis, Charles M Haberkern, Petra M Meier, Srijaya K Reddy, Thanh T Nguyen, Lingyu Cai, Marcia Polansky, Peter Szmuk, John Fiadjoe, Codruta Soneru, Ricardo Falcon, Timothy Petersen, Courtney Kowalczyk-Derderian, Nicholas Dalesio, Stefan Budac, Neels Groenewald, Daniel Rubens, Douglas Thompson, Rheana Watts, Katherine Gentry, Iskra Ivanova, Mali Hetmaniuk, Vincent Hsieh, Michael Collins, Karen Wong, Wendy Binstock, Russell Reid, Kim Poteet-Schwartz, Heike Gries, Rebecca Hall, Jeffrey Koh, Carolyn Bannister, Wai Sung, Ranu Jain, Allison Fernandez, Gerald F Tuite, Ernesto Ruas, Oleg Drozhinin, Lisa Tetreault, Bridget Muldowney, Karene Ricketts, Patrick Fernandez, Lisa Sohn, John Hajduk, Brad Taicher, Jessica Burkhart, Allison Wright, Jane Kugler, Lea Barajas-DeLoa, Meera Gangadharan, Veronica Busso, Kayla Stallworth, Susan Staudt, Kristen L Labovsky, Chris D Glover, Henry Huang, Helena Karlberg-Hippard, Samantha Capehart, Cynthia Streckfus, Kim-Phuong T Nguyen, Peter Manyang, Jose Luis Martinez, Jennifer K Hansen, Heather Mitzel Levy, Alyssa Brzenski, Franklin Chiao, Pablo Ingelmo, Razaz Mujallid, Olutoyin A Olutoye, Tariq Syed, Hubert Benzon, Adrian Bosenberg
BACKGROUND: The Pediatric Craniofacial Collaborative Group established the Pediatric Craniofacial Surgery Perioperative Registry to elucidate practices and outcomes in children with craniosynostosis undergoing complex cranial vault reconstruction and inform quality improvement efforts. The aim of this study is to determine perioperative management, outcomes, and complications in children undergoing complex cranial vault reconstruction across North America and to delineate salient features of current practices...
February 2017: Anesthesiology
https://www.readbyqxmd.com/read/27846392/a-druggable-tcf4-and-brd4-dependent-transcriptional-network-sustains-malignancy-in-blastic-plasmacytoid-dendritic-cell-neoplasm
#4
Michele Ceribelli, Zhiying Esther Hou, Priscilla N Kelly, Da Wei Huang, George Wright, Karthik Ganapathi, Moses O Evbuomwan, Stefania Pittaluga, Arthur L Shaffer, Guido Marcucci, Stephen J Forman, Wenming Xiao, Rajarshi Guha, Xiaohu Zhang, Marc Ferrer, Laurence Chaperot, Joel Plumas, Elaine S Jaffe, Craig J Thomas, Boris Reizis, Louis M Staudt
Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is an aggressive and largely incurable hematologic malignancy originating from plasmacytoid dendritic cells (pDCs). Using RNAi screening, we identified the E-box transcription factor TCF4 as a master regulator of the BPDCN oncogenic program. TCF4 served as a faithful diagnostic marker of BPDCN, and its downregulation caused the loss of the BPDCN-specific gene expression program and apoptosis. High-throughput drug screening revealed that bromodomain and extra-terminal domain inhibitors (BETis) induced BPDCN apoptosis, which was attributable to disruption of a BPDCN-specific transcriptional network controlled by TCF4-dependent super-enhancers...
November 14, 2016: Cancer Cell
https://www.readbyqxmd.com/read/27799566/epigenetic-gene-regulation-by-janus-kinase-1-in-diffuse-large-b-cell-lymphoma
#5
Lixin Rui, Amanda C Drennan, Michele Ceribelli, Fen Zhu, George W Wright, Da Wei Huang, Wenming Xiao, Yangguang Li, Kreg M Grindle, Li Lu, Daniel J Hodson, Arthur L Shaffer, Hong Zhao, Weihong Xu, Yandan Yang, Louis M Staudt
Janus kinases (JAKs) classically signal by activating STAT transcription factors but can also regulate gene expression by epigenetically phosphorylating histone H3 on tyrosine 41 (H3Y41-P). In diffuse large B-cell lymphomas (DLBCLs), JAK signaling is a feature of the activated B-cell (ABC) subtype and is triggered by autocrine production of IL-6 and IL-10. Whether this signaling involves STAT activation, epigenetic modification of chromatin, or both mechanisms is unknown. Here we use genetic and pharmacological inhibition to show that JAK1 signaling sustains the survival of ABC DLBCL cells...
November 15, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27551721/correction-type-2-diabetes-risk-allele-loci-in-the-qatari-population
#6
Sarah L O'Beirne, Jacqueline Salit, Juan L Rodriguez-Flores, Michelle R Staudt, Charbel Abi Khalil, Khalid A Fakhro, Amal Robay, Monica D Ramstetter, Iman K Al-Azwani, Joel A Malek, Mahmoud Zirie, Amin Jayyousi, Ramin Badii, Ajayeb Al-Nabet Al-Marri, Maria J Chiuchiolo, Alya Al-Shakaki, Omar Chidiac, Maey Gharbiah, Abdulbari Bener, Dora Stadler, Neil R Hackett, Jason G Mezey, Ronald G Crystal
[This corrects the article DOI: 10.1371/journal.pone.0156834.].
2016: PloS One
https://www.readbyqxmd.com/read/27408750/the-qatar-genome-a-population-specific-tool-for-precision-medicine-in-the-middle-east
#7
Khalid A Fakhro, Michelle R Staudt, Monica Denise Ramstetter, Amal Robay, Joel A Malek, Ramin Badii, Ajayeb Al-Nabet Al-Marri, Charbel Abi Khalil, Alya Al-Shakaki, Omar Chidiac, Dora Stadler, Mahmoud Zirie, Amin Jayyousi, Jacqueline Salit, Jason G Mezey, Ronald G Crystal, Juan L Rodriguez-Flores
Reaching the full potential of precision medicine depends on the quality of personalized genome interpretation. In order to facilitate precision medicine in regions of the Middle East and North Africa (MENA), a population-specific genome for the indigenous Arab population of Qatar (QTRG) was constructed by incorporating allele frequency data from sequencing of 1,161 Qataris, representing 0.4% of the population. A total of 20.9 million single nucleotide polymorphisms (SNPs) and 3.1 million indels were observed in Qatar, including an average of 1...
2016: Human Genome Variation
https://www.readbyqxmd.com/read/27389057/combined-copy-number-and-mutation-analysis-identifies-oncogenic-pathways-associated-with-transformation-of-follicular-lymphoma
#8
A Bouska, W Zhang, Q Gong, J Iqbal, A Scuto, J Vose, M Ludvigsen, K Fu, D D Weisenburger, T C Greiner, R D Gascoyne, A Rosenwald, G Ott, E Campo, L M Rimsza, J Delabie, E S Jaffe, R M Braziel, J M Connors, C-I Wu, L M Staudt, F D'Amore, T W McKeithan, W C Chan
Follicular lymphoma (FL) is typically an indolent disease, but 30-40% of FL cases transform into an aggressive lymphoma (tFL) with a poor prognosis. To identify the genetic changes that drive this transformation, we sequenced the exomes of 12 cases with paired FL and tFL biopsies and identified 45 recurrently mutated genes in the FL-tFL data set and 39 in the tFL cases. We selected 496 genes of potential importance in transformation and sequenced them in 23 additional tFL cases. Integration of the mutation data with copy-number abnormality (CNA) data provided complementary information...
January 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/27383215/type-2-diabetes-risk-allele-loci-in-the-qatari-population
#9
Sarah L O'Beirne, Jacqueline Salit, Juan L Rodriguez-Flores, Michelle R Staudt, Charbel Abi Khalil, Khalid A Fakhro, Amal Robay, Monica D Ramstetter, Iman K Al-Azwani, Joel A Malek, Mahmoud Zirie, Amin Jayyousi, Ramin Badii, Ajayeb Al-Nabet Al-Marri, Maria J Chiuchiolo, Alya Al-Shakaki, Omar Chidiac, Maey Gharbiah, Abdulbari Bener, Dora Stadler, Neil R Hackett, Jason G Mezey, Ronald G Crystal
BACKGROUND: The prevalence of type 2 diabetes (T2D) is increasing in the Middle East. However, the genetic risk factors for T2D in the Middle Eastern populations are not known, as the majority of studies of genetic risk for T2D are in Europeans and Asians. METHODS: All subjects were ≥3 generation Qataris. Cases with T2D (n = 1,124) and controls (n = 590) were randomly recruited and assigned to the 3 known Qatari genetic subpopulations [Bedouin (Q1), Persian/South Asian (Q2) and African (Q3)]...
2016: PloS One
https://www.readbyqxmd.com/read/27316455/molecular-determinants-that-mediate-the-sorting-of-human-atg9a-from-the-endoplasmic-reticulum
#10
Catherine Staudt, Florentine Gilis, Marielle Boonen, Michel Jadot
ATG9A is a multispanning membrane protein required for autophagosome formation. Under basal conditions, neosynthesized ATG9A proteins travel to the Golgi apparatus and cycle between the trans-Golgi network and endosomes. In the present work, we searched for molecular determinants involved in the subcellular trafficking of human ATG9A in HeLa cells using sequential deletions and point mutations. Deletion of amino acids L(340) to L(354) resulted in the retention of ATG9A in the endoplasmic reticulum. In addition, we found that substitution of the L(711)YM(713) sequence (located in the C-terminal region of ATG9A) by alanine residues severely impaired its transport through the Golgi apparatus...
September 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27070702/targeting-non-proteolytic-protein-ubiquitination-for-the-treatment-of-diffuse-large-b-cell-lymphoma
#11
COMPARATIVE STUDY
Yibin Yang, Priscilla Kelly, Arthur L Shaffer, Roland Schmitz, Hee Min Yoo, Xinyue Liu, Da Wei Huang, Daniel Webster, Ryan M Young, Masao Nakagawa, Michele Ceribelli, George W Wright, Yandan Yang, Hong Zhao, Xin Yu, Weihong Xu, Wing C Chan, Elaine S Jaffe, Randy D Gascoyne, Elias Campo, Andreas Rosenwald, German Ott, Jan Delabie, Lisa Rimsza, Louis M Staudt
Chronic active B cell receptor (BCR) signaling, a hallmark of the activated B cell-like (ABC) subtype of diffuse large B cell lymphoma (DLBCL), engages the CARD11-MALT1-BCL10 (CBM) adapter complex to activate IκB kinase (IKK) and the classical NF-κB pathway. Here we show that the CBM complex includes the E3 ubiquitin ligases cIAP1 and cIAP2, which are essential mediators of BCR-dependent NF-κB activity in ABC DLBCL. cIAP1/2 attach K63-linked polyubiquitin chains on themselves and on BCL10, resulting in the recruitment of IKK and the linear ubiquitin chain ligase LUBAC, which is essential for IKK activation...
April 11, 2016: Cancer Cell
https://www.readbyqxmd.com/read/27007171/pulmonary-abnormalities-in-young-light-use-waterpipe-hookah-smokers
#12
Yael Strulovici-Barel, Renat Shaykhiev, Jacqueline Salit, Ruba S Deeb, Anja Krause, Robert J Kaner, Thomas L Vincent, Francisco Agosto-Perez, Guoqing Wang, Charleen Hollmann, Vignesh Shanmugam, Ahmad M Almulla, Hisham Sattar, Mai Mahmoud, Jason G Mezey, Steven S Gross, Michelle R Staudt, Matthew S Walters, Ronald G Crystal
RATIONALE: Waterpipes, also called hookahs, are currently used by millions of people worldwide. Despite the increasing use of waterpipe smoking, there is limited data on the health effects of waterpipe smoking and there are no federal regulations regarding its use. OBJECTIVES: To assess the effects of waterpipe smoking on the human lung using clinical and biological parameters in young, light-use waterpipe smokers. METHODS: We assessed young, light-use, waterpipe-only smokers in comparison with lifelong nonsmokers using clinical parameters of cough and sputum scores, lung function, and chest high-resolution computed tomography as well as biological parameters of lung epithelial lining fluid metabolome, small airway epithelial (SAE) cell differential and transcriptome, alveolar macrophage transcriptome, and plasma apoptotic endothelial cell microparticles...
September 1, 2016: American Journal of Respiratory and Critical Care Medicine
https://www.readbyqxmd.com/read/26993806/regulation-of-normal-b-cell-differentiation-and-malignant-b-cell-survival-by-oct2
#13
Daniel J Hodson, Arthur L Shaffer, Wenming Xiao, George W Wright, Roland Schmitz, James D Phelan, Yandan Yang, Daniel E Webster, Lixin Rui, Holger Kohlhammer, Masao Nakagawa, Thomas A Waldmann, Louis M Staudt
The requirement for the B-cell transcription factor OCT2 (octamer-binding protein 2, encoded by Pou2f2) in germinal center B cells has proved controversial. Here, we report that germinal center B cells are formed normally after depletion of OCT2 in a conditional knockout mouse, but their proliferation is reduced and in vivo differentiation to antibody-secreting plasma cells is blocked. This finding led us to examine the role of OCT2 in germinal center-derived lymphomas. shRNA knockdown showed that almost all diffuse large B-cell lymphoma (DLBCL) cell lines are addicted to the expression of OCT2 and its coactivator OCA-B...
April 5, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/26820358/combination-of-forward-osmosis-fo-process%C3%A2-with-coagulation-flocculation-cf-for-potential-treatment-of-textile-wastewater
#14
Gang Han, Can-Zeng Liang, Tai-Shung Chung, Martin Weber, Claudia Staudt, Christian Maletzko
A novel combination of forward osmosis (FO) process with coagulation/flocculation (CF) (FO-CF) has been experimentally conceived for the treatment and reuse of textile wastewater. FO is employed to spontaneously recover water from the wastewater via osmosis and thus effectively reduces its volume with a dramatically enhanced dye concentration. CF is then applied to precipitate and remove dyes from the FO concentrated stream with much improved efficiency and reduced chemical dosage. The FO-CF hybrid system exhibits unique advantages of high water flux and recovery rate, well controlled membrane fouling, high efficiency, and minimal environmental impact...
March 15, 2016: Water Research
https://www.readbyqxmd.com/read/26787899/subtype-specific-addiction-of-the-activated-b-cell-subset-of-diffuse-large-b-cell-lymphoma-to-foxp1
#15
Joseph D Dekker, Daechan Park, Arthur L Shaffer, Holger Kohlhammer, Wei Deng, Bum-Kyu Lee, Gregory C Ippolito, George Georgiou, Vishwanath R Iyer, Louis M Staudt, Haley O Tucker
High expression of the forkhead box P1 (FOXP1) transcription factor distinguishes the aggressive activated B cell (ABC) diffuse large B-cell lymphoma (DLBCL) subtype from the better prognosis germinal center B-cell (GCB)-DLBCL subtype and is highly correlated with poor outcomes. A genetic or functional role for FOXP1 in lymphomagenesis, however, remains unknown. Here, we report that sustained FOXP1 expression is vital for ABC-DLBCL cell-line survival. Genome-wide analyses revealed direct and indirect FOXP1 transcriptional enforcement of ABC-DLBCL hallmarks, including the classical NF-κB and MYD88 (myeloid differentiation primary response gene 88) pathways...
February 2, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/26785329/treadmill-measures-of-ambulation-rates-in-ovine-models-of-spinal-cord-injury-and-neuropathic-pain
#16
S Safayi, J W Miller, S Wilson, S K Shivapour, T F Oelfke, A L Ford, A Klarmann Staudt, K Abode-Iyamah, C G Reddy, N D Jeffery, D C Fredericks, G T Gillies, M A Howard
Our laboratories are developing treadmill-based gait analysis employing sheep to investigate potential efficacy of intra-dural spinal cord stimulation in the treatment of spinal cord injury and neuropathic pain. As part of efforts to establish the performance characteristics of the experimental arrangement, this study measured the treadmill speed via a tachometer, video belt-marker timing and ambulation-rate observations of the sheep. The data reveal a 0.1-0.3% residual drift in the baseline (unloaded) treadmill speed which increases with loading, but all three approaches agree on final speed to within 1...
2016: Journal of Medical Engineering & Technology
https://www.readbyqxmd.com/read/26719098/recurrent-activating-mutations-of-cd28-in-peripheral-t-cell-lymphomas
#17
J Rohr, S Guo, J Huo, A Bouska, C Lachel, Y Li, P D Simone, W Zhang, Q Gong, C Wang, A Cannon, T Heavican, A Mottok, S Hung, A Rosenwald, R Gascoyne, K Fu, T C Greiner, D D Weisenburger, J M Vose, L M Staudt, W Xiao, G E O Borgstahl, S Davis, C Steidl, T McKeithan, J Iqbal, W C Chan
Peripheral T-cell lymphomas (PTCLs) comprise a heterogeneous group of mature T-cell neoplasms with a poor prognosis. Recently, mutations in TET2 and other epigenetic modifiers as well as RHOA have been identified in these diseases, particularly in angioimmunoblastic T-cell lymphoma (AITL). CD28 is the major co-stimulatory receptor in T cells which, upon binding ligand, induces sustained T-cell proliferation and cytokine production when combined with T-cell receptor stimulation. We have identified recurrent mutations in CD28 in PTCLs...
May 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/26621451/selective-interleukin-1-receptor-associated-kinase-4-inhibitors-for-the-treatment-of-autoimmune-disorders-and-lymphoid-malignancy
#18
Priscilla N Kelly, Donna L Romero, Yibin Yang, Arthur L Shaffer, Divya Chaudhary, Shaughnessy Robinson, Wenyan Miao, Lixin Rui, William F Westlin, Rosana Kapeller, Louis M Staudt
Pathological activation of the Toll-like receptor signaling adaptor protein MYD88 underlies many autoimmune and inflammatory disease states. In the activated B cell-like (ABC) subtype of diffuse large B cell lymphoma (DLBCL), the oncogenic MYD88 L265P mutation occurs in 29% of cases, making it the most prevalent activating mutation in this malignancy. IRAK4 kinase accounts for almost all of the biological functions of MYD88, highlighting IRAK4 as a therapeutic target for diseases driven by aberrant MYD88 signaling...
December 14, 2015: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/26490036/copy-number-variations-in-the-genome-of-the-qatari-population
#19
Khalid A Fakhro, Noha A Yousri, Juan L Rodriguez-Flores, Amal Robay, Michelle R Staudt, Francisco Agosto-Perez, Jacqueline Salit, Joel A Malek, Karsten Suhre, Amin Jayyousi, Mahmoud Zirie, Dora Stadler, Jason G Mezey, Ronald G Crystal
BACKGROUND: The populations of the Arabian Peninsula remain the least represented in public genetic databases, both in terms of single nucleotide variants and of larger genomic mutations. We present the first high-resolution copy number variation (CNV) map for a Gulf Arab population, using a hybrid approach that integrates array genotyping intensity data and next-generation sequencing reads to call CNVs in the Qatari population. METHODS: CNVs were detected in 97 unrelated Qatari individuals by running two calling algorithms on each of two primary datasets: high-resolution genotyping (Illumina Omni 2...
October 22, 2015: BMC Genomics
https://www.readbyqxmd.com/read/26465791/growth-nutrition-and-cytokine-response-of-breast-fed-infants-and-infants-fed-formula-with-added-bovine-osteopontin
#20
RANDOMIZED CONTROLLED TRIAL
Bo Lönnerdal, Anne S Kvistgaard, Janet M Peerson, Sharon M Donovan, Yong-mei Peng
OBJECTIVES: Breast milk contains a high concentration of osteopontin (OPN), a protein having multiple functions. In contrast, infant formula is low in OPN. A randomized clinical trial was performed to evaluate effects of adding a highly enriched bovine OPN fraction to formula, and infants whose mothers had already decided not to breast-feed were recruited. They were fed regular formula (F0) or the same formula with bovine OPN at 65 (F65) or 130 (F130) mg/L (50% and 100% of human milk level, respectively) from 1 to 6 months of age and were compared with a reference group of breast-fed (BF) infants...
April 2016: Journal of Pediatric Gastroenterology and Nutrition
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