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https://www.readbyqxmd.com/read/29234922/pharmacokinetically-targeted-dosed-everolimus-maintenance-therapy-in-lymphoma-patients
#1
L K Schoch, A Asiama, M Zahurak, S Shanbhag, J Hurtt, K Sawyer, L J Swinnen, N Wagner-Johnston, R J Jones, R F Ambinder, Douglas E Gladstone
BACKGROUND: Everolimus, an mTOR inhibitor, is active in refractory lymphomas. However, toxicity with flat dosing limits its usage. Speculatively, pharmacokinetically-targeted dosing could improve tolerability. Therefore, we studied serum-trough dosing with rituximab as maintenance after high-dose cyclophosphamide (HDC) consolidation in lymphoma patients. PATIENTS/METHODS: After HDC, everolimus was dosed to serum trough levels (goal 3-15 ng/mL), with quarterly rituximab infusions for 1 year while maintaining < grade II non-hematologic and < grade III hematologic toxicities...
December 13, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/29232168/high-throughput-screening-approach-for-identifying-compounds-that-inhibit-nonhomologous-end-joining
#2
Andrea L Bredemeyer, Bruce S Edwards, Mark K Haynes, Abigail J Morales, Yinan Wang, Oleg Ursu, Anna Waller, Larry A Sklar, Barry P Sleckman
DNA double-strand breaks (DSBs) are repaired primarily by homologous recombination (HR) or nonhomologous end joining (NHEJ). Compounds that modulate HR have shown promise as cancer therapeutics. The V(D)J recombination reaction, which assembles antigen receptor genes in lymphocytes, is initiated by the introduction of DNA DSBs at two recombining gene segments by the RAG endonuclease, followed by the NHEJ-mediated repair of these DSBs. Here, using HyperCyt automated flow cytometry, we develop a robust high-throughput screening (HTS) assay for NHEJ that utilizes engineered pre-B-cell lines where the V(D)J recombination reaction can be induced and monitored at a single-cell level...
December 1, 2017: SLAS Discovery
https://www.readbyqxmd.com/read/29230670/double-somatic-smarcb1-and-nf2-mutations-in-sporadic-spinal-schwannoma
#3
Irene Paganini, Gabriele Lorenzo Capone, Jeremie Vitte, Roberta Sestini, Anna Laura Putignano, Marco Giovannini, Laura Papi
In sporadic schwannomas, inactivation of both copies of the NF2 tumor suppressor gene on 22q is common. Constitutional mutations of SMARCB1 are responsible of schwannomatosis, an inherited tumor predisposition syndrome, characterized by the development of multiple schwannomas. We analysed the frequency of copy number changes on chromosome 22 and the mutation of NF2 and SMARCB1 in 26 sporadic schwannomas. We found two spinal schwannomas with an identical somatic missense mutation in SMARCB1 exon 9: p.(Arg377His)...
December 11, 2017: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/29225339/early-speech-development-in-koolen-de-vries-syndrome-limited-by-oral-praxis-and-hypotonia
#4
Angela T Morgan, Leenke van Haaften, Karen van Hulst, Carol Edley, Cristina Mei, Tiong Yang Tan, David Amor, Simon E Fisher, David A Koolen
Communication disorder is common in Koolen de Vries syndrome (KdVS), yet its specific symptomatology has not been examined, limiting prognostic counselling and application of targeted therapies. Here we examine the communication phenotype associated with KdVS. Twenty-nine participants (12 males, 4 with KANSL1 variants, 25 with 17q21.31 microdeletion), aged 1.0-27.0 years were assessed for oral-motor, speech, language, literacy, and social functioning. Early history included hypotonia and feeding difficulties...
December 11, 2017: European Journal of Human Genetics: EJHG
https://www.readbyqxmd.com/read/29222269/current-treatment-of-double-hit-and-double-expressor-lymphoma
#5
REVIEW
Patrick M Reagan, Andrew Davies
A 60-year-old female presented with abdominal pain and distension. Following computed tomography scans of the abdomen and pelvis, she was taken urgently to the operating room, with the belief that she had appendicitis with perforation. At laparotomy, the findings were consistent with an ovarian carcinoma; there was extensive infiltration of the ovary, bowel, and omental deposits. Cytoreductive surgery was performed including total abdominal hysterectomy and bilateral salpingo-oophorectomy. The final pathology, however, revealed infiltration with medium-sized atypical lymphoid cells positive for CD20, CD10, MYC, BLC2, and BCL6 by immunohistochemistry...
December 8, 2017: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/29222268/tailoring-front-line-therapy-in-diffuse-large-b-cell-lymphoma-who-should-we-treat-differently
#6
REVIEW
Andrew Davies
Although there have been significant insights into the biology of diffuse large B-cell lymphoma (DLBCL) over recent years, progress in our therapeutic approach has been disappointing over the same timeframe. This is not for want of trying. In 2017, R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone) remains the "gold standard," despite all of our insights into cell-of-origin and other subgroups. We have traditionally used clinical risk factors to tailor our therapies and have tested intensification of chemotherapy with little success...
December 8, 2017: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/29215417/muramyl-dipeptide-enhances-thermal-injury-induced-autophagy-and-inflammatory-cytokine-response-of-lungs-via-activation-of-nod2-rick-signaling-pathway-in-rats
#7
Xiao-Jing Wu, Hui Liang, Ying Zhang, Xu-Ming Yang, Hong-Yu Wang, Hui Li, Xin-Yi Li, Kai Chen, Yan-Lin Wang, Jian-Guo Li, Zong-Ze Zhang, Xue-Min Song
OBJECTIVE: Nucleotide-binding oligomerization domain 2 (NOD2) is the innate receptor of muramyl dipeptide (MDP). Our previous study revealed that MDP could enhance thermal injury-induced inflammatory cytokine production and organ function injury in rats. The present study was to determine the effect of MDP on autophagy and NOD2/receptor-interacting serine/threonine protein kinases (RICK) signaling pathway of lung injury after thermal injury. METHODS: Forty male Sprague-Dawlay rats were randomly divided into four groups: normal control (NC) group, MDP group, Scald group and MDP + Scald group...
December 6, 2017: Shock
https://www.readbyqxmd.com/read/29208429/checkpoint-inhibitors-and-aspergillosis-in-aml-the-double-hit-hypothesis
#8
Naval Daver, Dimitrios P Kontoyiannis
No abstract text is available yet for this article.
December 2017: Lancet Oncology
https://www.readbyqxmd.com/read/29204378/circular-mitochondrial-dna-a-geant4-dna-user-application-for-evaluating-radiation-induced-damage-in-circular-mitochondrial-dna
#9
Mohammad Bagher Tavakoli, Habiballah Moradi, Hossein Khanahmad, Mohsen Hosseini
Background: The aim of this study was to develop a nucleotide geometrical model of the circular mitochondrial DNA (mt-DNA) structure using Geant4-DNA toolkit to predict the radiation-induced damages such as single-strand breaks (SSB), double-strand breaks (DSB), and some other physical parameters. Methods: Our model covers the organization of a circular human mt genetic system. The current model includes all 16,659 base pairs of human mt-DNA. This new mt-DNA model has been preliminarily tested in this work by determining SSB and DSB DNA damage yields and site-hit probabilities due to the impact of proton particles...
October 2017: Journal of Medical Signals and Sensors
https://www.readbyqxmd.com/read/29199519/outcomes-of-da-epoch-r-induction-plus-autologous-transplant-consolidation-for-double-hit-lymphoma
#10
Andy I Chen, Jessica T Leonard, Craig Y Okada, Nathan D Gay, Kari Chansky, Guang Fan, Jennifer B Dunlap, Philipp W Raess, Rita M Braziel, Alex Stentz, Richard T Maziarz
High-grade B cell lymphoma with MYC and BCL2 rearrangements (double hit) has a poor prognosis with standard R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone). We report here a treatment algorithm of DA-EPOCH-R (dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, rituximab) followed by BEAM (carmustine, etoposide, cytarabine, melphalan) autologous transplant in 36 cases of previously untreated double hit lymphoma (DHL) from 2010 to 2015. A high risk International Prognostic Index (IPI) was present in 42% of cases...
December 3, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/29196080/outcomes-after-allogeneic-stem-cell-transplantation-in-patients-with-double-hit-and-double-expressor-lymphoma
#11
Alex F Herrera, Scott J Rodig, Joo Y Song, Young Kim, Gabriel K Griffin, Dongyun Yang, Liana Nikolaenko, Matthew Mei, Victoria Bedell, Paola Dal Cin, Christine Pak, Edwin P Alyea, Elizabeth Budde, Robert Chen, Yi-Bin Chen, Wing C Chan, Corey S Cutler, Vincent T Ho, John Koreth, Amrita Krishnan, Joyce L Murata-Collins, Sarah Nikiforow, Joycelynne Palmer, German A Pihan, Raju Pillai, Leslie Popplewell, Steven T Rosen, Tanya Siddiqi, Aliyah R Sohani, Jasmine Zain, Larry W Kwak, Dennis D Weisenburger, David M Weinstock, Robert J Soiffer, Joseph H Antin, Stephen J Forman, Auayporn P Nademanee, Philippe Armand
Double-hit lymphomas (DHL) and double-expressor lymphomas (DEL) are associated with resistance to frontline and salvage immunochemotherapy, as well as autologous stem cell transplantation (SCT). We hypothesized that allogeneic SCT (alloSCT) could overcome the chemoresistance associated with DEL/DHL. We retrospectively studied the impact of DEL/DHL status in a multicenter cohort of patients who underwent alloSCT for relapsed/refractory (rel/ref) aggressive B-cell non-Hodgkin lymphoma (B-NHL). 78 patients transplanted at 3 centers in whom tumor tissue was available for immunohistochemistry and FISH were enrolled; 47% had DEL and 13% had DHL...
November 28, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/29194741/-double-hit-chronic-lymphocytic-leukemia-an-aggressive-subgroup-with-17p-deletion-and-8q24-gain
#12
Elise Chapiro, Claude Lesty, Clémentine Gabillaud, Eric Durot, Simon Bouzy, Marine Armand, Magali Le Garff-Tavernier, Nadia Bougacha, Stéphanie Struski, Audrey Bidet, Elodie Laharanne, Carole Barin, Lauren Veronese, Nolwen Prié, Virginie Eclache, Baptiste Gaillard, Lucienne Michaux, Christine Lefebvre, Jean-Baptiste Gaillard, Christine Terré, Dominique Penther, Christian Bastard, Nathalie Nadal, Sandra Fert-Ferrer, Nathalie Auger, Catherine Godon, Laurent Sutton, Olivier Tournilhac, Santos A Susin, Florence Nguyen-Khac
Chronic lymphocytic leukemia (CLL) with 17p deletion (17p-) is associated with a lack of response to standard treatment and thus the worst possible clinical outcome. Various chromosomal abnormalities (including unbalanced translocations, deletions, ring chromosomes and isochromosomes) result in the loss of 17p and one copy of the TP53 gene. The objective of the present study was to determine whether the type of chromosomal abnormality leading to 17p- and the additional aberrations influenced the prognosis in a series of 195 patients with 17p-CLL...
December 1, 2017: American Journal of Hematology
https://www.readbyqxmd.com/read/29194093/cdkn2a-b-deletion-and-double-hit-mutations-of-the-mapk-pathway-underlie-the-aggressive-behavior-of-langerhans-cell-tumors
#13
Luc Xerri, José Adélaïde, Cornel Popovici, Séverine Garnier, Arnaud Guille, Lenaïg Mescam-Mancini, Camille Laurent, Pierre Brousset, Carole Coze, Gérard Michel, Max Chaffanet, Reda Bouabdallah, Diane Coso, François Bertucci, Daniel Birnbaum
Langerhans cell histiocytosis (LCH) has a mostly favorable outcome, whereas Langerhans cell sarcoma (LCS) is an aggressive tumor. It is still unclear whether any specific molecular alterations could underlie the aggressive behavior of Langerhans cell proliferations. We used targeted next-generation sequencing and array-comparative genomic hybridization to profile 22 LCH samples from different patients together with 3 LCS samples corresponding to different relapses from the same patient. The third LCS relapse was a composite tumor including both B-cell chronic lymphocytic leukemia and LCS components...
November 29, 2017: American Journal of Surgical Pathology
https://www.readbyqxmd.com/read/29176735/interplay-between-trauma-and-pseudomonas-entomophila-infection-in-flies-a-central-role-of-the-jnk-pathway-and-of-creba
#14
Ramy Ragheb, Alexandre Chuyen, Magali Torres, Arnaud Defaye, Denis Seyres, Laurent Kremmer, Nicolas Fernandez-Nunez, Hervé Tricoire, Pascal Rihet, Catherine Nguyen, Laurence Röder, Laurent Perrin
In mammals, both sterile wounding and infection induce inflammation and activate the innate immune system, and the combination of both challenges may lead to severe health defects, revealing the importance of the balance between the intensity and resolution of the inflammatory response for the organism's fitness. Underlying mechanisms remain however elusive. Using Drosophila, we show that, upon infection with the entomopathogenic bacterium Pseudomonas entomophila (Pe), a sterile wounding induces a reduced resistance and increased host mortality...
November 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29140130/the-effects-of-hydrogen-peroxide-and-lipopolysaccharide-on-rat-alveolar-l2-cells
#15
Eun Kyeong Kang, Han Suk Kim
PURPOSE: This study aimed to investigate differential cell responses of alveolar epithelial cells (AECs) after treatments with lipopolysaccharide (LPS) and hydrogen peroxide (H2O2) to mimic the exposure to inflammation and oxidative stress and the mechanisms of a double-hit model of apoptosis. MATERIALS AND METHODS: AECs were cultured and treated with combinations of 1 μg/mL of LPS and 500 μM H2O2 as follows: LPS-only at 0 h, LPS at 0 h with H2O2 at 6 h (LPS + H2O2), H2O2-only at 0 h, H2O2 at 0 h with LPS at 6 h (H2O2 + LPS), and control...
October 2017: Experimental Lung Research
https://www.readbyqxmd.com/read/29126866/advances-in-diagnosis-and-management-of-diffuse-large-b-cell-lymphoma
#16
REVIEW
Fernando Cabanillas, Bijal Shah
The management of diffuse large B-cell lymphoma (DLBCL) has been gradually evolving since the discovery of its 2 major forms, the germinal center B-like (GCB) and activated B-cell (ABC) types. Although the reference standard for the identification of these cell types is considered gene expression profiling (GEP), currently the only method commercially available is immunohistochemistry (IHC). The application of various IHC-based algorithms and their correlation with GEP and clinical outcome are discussed. Because of the adverse prognostic implications of the non-GCB type and its potential effects on treatment selection, the recently revised World Health Organization classification has included these biologic cell types...
December 2017: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/29117924/red-flags-in-epilepsy-surgery-identifying-the-patients-who-pay-a-high-cognitive-price-for-an-unsuccessful-surgical-outcome
#17
Sallie Baxendale, Pamela Thompson
Preoperative estimates of cognitive and seizure outcome must be as accurate as possible if the candidate is to make an informed decision about epilepsy surgery. Significant declines in memory function are reported in approximately 30% of temporal lobe surgery patients. The percentage varies according to the ways in which a postoperative deterioration is defined but since the majority of outcome studies do not take into account the patient's capacity to deteriorate if they are functioning at or close to the floor of a memory test prior to surgery, the published percentages may be an underrepresentation of the true extent of memory decline following epilepsy surgery...
November 5, 2017: Epilepsy & Behavior: E&B
https://www.readbyqxmd.com/read/29108217/advancing-the-management-of-double-hit-lymphoma
#18
EDITORIAL
Daniel J Landsburg
No abstract text is available yet for this article.
October 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/29103474/effectiveness-and-cost-effectiveness-of-double-reading-in-digital-mammography-screening-a-systematic-review-and-meta-analysis
#19
Margarita Posso, Teresa Puig, Misericòrdia Carles, Montserrat Rué, Carlos Canelo-Aybar, Xavier Bonfill
PURPOSE: Double reading is the strategy of choice for mammogram interpretation in screening programmes. It remains, however, unknown whether double reading is still the strategy of choice in the context of digital mammography. Our aim was to determine the effectiveness and cost-effectiveness of double reading versus single reading of digital mammograms in screening programmes. METHODS: We performed a systematic review by searching the PubMed, Embase, and Cochrane Library databases up to April 2017...
November 2017: European Journal of Radiology
https://www.readbyqxmd.com/read/28990169/methylphenidate-cognition-and-epilepsy-a-1-month-open-label-trial
#20
Jesse Adams, Valerie Alipio-Jocson, Katherine Inoyama, Victoria Bartlett, Saira Sandhu, Jemima Oso, John J Barry, David W Loring, Kimford J Meador
OBJECTIVE: Cognitive difficulties are common in epilepsy. Beyond reducing seizures and adjusting antiepileptic medications, no well-validated treatment exists in adults. Methylphenidate is used effectively in children with epilepsy and attention-deficit/hyperactivity disorder, but its effects in adults have not been systematically evaluated. We hypothesized that methylphenidate can safely improve cognition in adults with epilepsy. We detail here the open-label follow-up to a double-blind, placebo-controlled, single-dose study...
October 9, 2017: Epilepsia
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