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Double-hit

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https://www.readbyqxmd.com/read/28615297/disruption-of-aneuploidy-and-senescence-induced-by-aurora-inhibition-promotes-intrinsic-apoptosis-in-double-hit-or-double-expressor-diffuse-large-b-cell-lymphomas
#1
Daruka Mahadevan, Shariful Islam, Wenqing Qi, Carla Morales, Laurence Cooke, Catherine Spier, Eric Weterings
Double Hit (DH) or Double Expressor (DE) diffuse large B-cell lymphoma (DLBCL) are aggressive Non-Hodgkin's Lymphomas (NHLs) with translocations and/or over-expressions of MYC and BCL-2, that are difficult to treat. Aurora kinase (AK) inhibition with alisertib in DH/DE-DLBCL induces cell death in ~30%, while ~70% are aneuploid and senescent cells (AASCs), a mitotic escape mechanism contributing to drug resistance. These AASCs elaborated a high metabolic rate by increased AKT/mTOR and ERK/MAPK activity via BTK signaling through the chronic active B-cell receptor (BCR) pathway...
June 14, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28600333/how-i-treat-double-hit-lymphoma
#2
Jonathan W Friedberg
The 2016 revision of the WHO classification for lymphoma classification has included a new category of lymphoma, separate from diffuse large B-cell lymphoma termed High grade B-cell lymphoma with translocations involving myc and bcl-2 or bcl-6 These lymphomas, which occur in less than 10% of cases of diffuse large B-cell lymphoma, have been referred to as "double hit" lymphomas (or triple hit lymphomas if all three rearrangements are present). It is important to differentiate these lymphomas from the larger group of "double expressor" lymphomas which have increased expression of MYC and BCL-2 and/or BCL-6 by immunohistochemistry, using variable cut-off percentages to define positivity...
June 9, 2017: Blood
https://www.readbyqxmd.com/read/28595732/the-novel-double-hit-t-8-22-q24-q11-myc-igl-and-t-14-15-q32-q24-igh-bcl2a1-in-diffuse-large-b-cell-lymphoma
#3
Takashi Akasaka, Chiyuki Kishimori, Katsuhiro Fukutsuka, Miho Nakagawa, Kayo Takeoka, Masahiko Hayashida, Gen Honjo, Hitoshi Ohno
An 82-year-old woman presented with generalized lymphadenopathy and skin involvement. Lymph node biopsy revealed diffuse large B-cell lymphoma with a high proliferation index. G-banding and fluorescence in situ hybridization showed a hypertetraploid karyotype with two copies of t(8;22)(q24;q11), generating the fusion of MYC and the immunoglobulin λ chain gene (IGL), and two copies of the novel immunoglobulin heavy chain gene (IGH) translocation, t(14;15)(q32;q24). A long-distance inverse polymerase chain reaction (PCR) using nested primer combinations designed for each constant gene of IGH showed that Cγ4 was juxtaposed to the downstream sequence of the BCL2A1 (BCL2-related protein A1) gene through the Sγ4 switch region...
August 2017: Cancer Genetics
https://www.readbyqxmd.com/read/28585211/non-alcoholic-fatty-liver-disease
#4
Atilla Engin
Non-alcoholic fatty liver disease (NAFLD) is in parallel with the obesity epidemic and it is the most common cause of liver diseases. The development of hepatic steatosis in majority of patients is linked to dietary fat ingestion. NAFLD is characterized by excess accumulation of triglyceride in the hepatocyte due to both increased inflow of free fatty acids and de novo hepatic lipogenesis. Insulin resistance with the deficiency of insulin receptor substrate-2 (IRS-2)-associated phosphatidylinositol 3-kinase (PI3K) activity causes an increase in intracellular fatty acid-derived metabolites such as diacylglycerol, fatty acyl CoA or ceramides...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28584253/prediction-of-outcome-in-newly-diagnosed-myeloma-a-meta-analysis-of-the-molecular-profiles-of-1-905-trial-patients
#5
V Shah, A L Sherborne, B A Walker, D C Johnson, E M Boyle, S Ellis, D B Begum, P Z Proszek, J R Jones, C Pawlyn, S Savola, M W Jenner, M T Drayson, R G Owen, R S Houlston, D A Cairns, W M Gregory, G Cook, F E Davies, G H Jackson, G J Morgan, M F Kaiser
Robust establishment of survival in multiple myeloma (MM) and its relationship to recurrent genetic aberrations is required as outcomes are variable despite apparent similar staging. We assayed copy number alterations (CNA) and translocations in 1036 patients from the NCRI Myeloma XI trial and linked these to overall survival (OS) and progression-free survival. Through a meta-anlysis of these data with data from MRC Myeloma IX trial, totalling 1905 newly diagnosed MM patients (NDMM), we confirm the association of t(4;14), t(14;16), t(14;20), del(17p) and gain(1q21) with poor prognosis with hazard ratios (HRs) for OS of 1...
June 6, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28583411/increased-temporal-discounting-after-chronic-stress-in-chl1-deficient-mice-is-reversed-by-5-ht2c-agonist-ro-60-0175
#6
Mona Buhusi, Kaitlin Olsen, Catalin V Buhusi
Schizophrenia is a neurodevelopmental disorder in which impaired decision-making and goal-directed behaviors are core features. One of the genes associated with schizophrenia is the Close Homolog of L1 (CHL1); CHL1-deficient mice are considered a model of schizophrenia-like deficits, including sensorimotor gating, interval timing and spatial memory impairments. Here we investigated temporal discounting in CHL1-deficient (KO) mice and their wild-type littermates. Although no discounting differences were found under baseline conditions, CHL1-KO mice showed increased impulsive choice following chronic unpredictable stress (fewer % larger-later choices, and reduced area under the discounting curve)...
June 3, 2017: Neuroscience
https://www.readbyqxmd.com/read/28579851/transformation-of-follicular-lymphoma-to-a-high-grade-b-cell-lymphoma-with-myc-and-bcl2-translocations-and-overlapping-features-of-burkitt-lymphoma-and-acute-lymphoblastic-leukemia-a-case-report-and-literature-review
#7
Alina M Bischin, Russell Dorer, David M Aboulafia
Most commonly, histologic transformation (HT) from follicular lymphoma (FL) manifests as a diffuse large B-cell lymphoma, not otherwise specified (DLBCL, NOS). Less frequently, HT may result in a high-grade B-cell lymphoma (HGBL) with MYC and B-cell lymphoma protein 2 (BCL2) and/or BCL6 gene rearrangements, also known as "double-hit" or "triple-hit" lymphomas. In the 2016 revision of the World Health Organization (WHO) classification of lymphoid neoplasms, the category B-cell lymphoma, unclassifiable was eliminated due to its vague criteria and limiting diagnostic benefit...
2017: Clinical Medicine Insights. Blood Disorders
https://www.readbyqxmd.com/read/28512105/double-hit-lymphoma-presenting-as-haemophagocytic-lymphohistiocytosis
#8
Xavier Issac Rivera, Lee J McGhan, Jonathan H Schatz, Soham D Puvvada
No abstract text is available yet for this article.
May 15, 2017: BMJ Case Reports
https://www.readbyqxmd.com/read/28496415/inflammatory-effects-of-menthol-vs-non-menthol-cigarette-smoke-extract-on-human-lung-epithelial-cells-a-double-hit-on-trpm8-by-reactive-oxygen-species-and-menthol
#9
An-Hsuan Lin, Meng-Han Liu, Hsin-Kuo B Ko, Diahn-Warng Perng, Tzong-Shyuan Lee, Yu Ru Kou
Clinical studies suggest that smokers with chronic obstructive pulmonary disease who use menthol cigarettes may display more severe lung inflammation than those who smoke non-menthol cigarette. However, the mechanisms for this difference remain unclear. Menthol is a ligand of transient receptor potential melastatin-8 (TRPM8), a Ca(2+)-permeant channel sensitive to reactive oxygen species (ROS). We previously reported that exposure of human bronchial epithelial cells (HBECs) to non-menthol cigarette smoke extract (Non-M-CSE) triggers a cascade of inflammatory signaling leading to IL-8 induction...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28486099/a-tiam-double-hit-to-oppose-yap-taz
#10
Luca Azzolin, Stefano Piccolo
In this issue of Cancer Cell, Diamantopoulou et al. uncover dual mechanisms of inhibiting YAP/TAZ by TIAM1 that oppose invasiveness of colorectal cancer cells: TIAM1 interacts with TAZ in the cytoplasm to promote TAZ degradation by the destruction complex, whereas it antagonizes binding of TAZ/YAP to TEAD in the nucleus.
May 8, 2017: Cancer Cell
https://www.readbyqxmd.com/read/28475457/outcomes-of-patients-with-double-hit-lymphoma-who-achieve-first-complete-remission
#11
Daniel J Landsburg, Marissa K Falkiewicz, Joseph Maly, Kristie A Blum, Christina Howlett, Tatyana Feldman, Anthony R Mato, Brian T Hill, Shaoying Li, L Jeffrey Medeiros, Pallawi Torka, Francisco Hernandez-Ilizaliturri, Nishitha M Reddy, Arun Singavi, Timothy S Fenske, Julio C Chavez, Jason B Kaplan, Amir Behdad, Adam M Petrich, Martin A Bast, Julie M Vose, Adam J Olszewski, Cristiana Costa, Frederick Lansigan, James N Gerson, Stefan K Barta, Oscar Calzada, Jonathon B Cohen, Jennifer K Lue, Jennifer E Amengual, Xavier Rivera, Daniel O Persky, David J Peace, Sunita Nathan, Ryan D Cassaday
Purpose Patients with double-hit lymphoma (DHL) rarely achieve long-term survival following disease relapse. Some patients with DHL undergo consolidative autologous stem-cell transplantation (autoSCT) to reduce the risk of relapse, although the benefit of this treatment strategy is unclear. Methods Patients with DHL who achieved first complete remission following completion of front-line therapy with either rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) or intensive front-line therapy, and deemed fit for autoSCT, were included...
May 5, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28466069/early-social-isolation-stress-and-perinatal-nmda-receptor-antagonist-treatment-induce-changes-in-the-structure-and-neurochemistry-of-inhibitory-neurons-of-the-adult-amygdala-and-prefrontal-cortex
#12
Esther Castillo-Gómez, Marta Pérez-Rando, María Bellés, Javier Gilabert-Juan, José Vicente Llorens, Héctor Carceller, Clara Bueno-Fernández, Clara García-Mompó, Beatriz Ripoll-Martínez, Yasmina Curto, Noelia Sebastiá-Ortega, María Dolores Moltó, Julio Sanjuan, Juan Nacher
The exposure to aversive experiences during early life influences brain development and leads to altered behavior. Moreover, the combination of these experiences with subtle alterations in neurodevelopment may contribute to the emergence of psychiatric disorders, such as schizophrenia. Recent hypotheses suggest that imbalances between excitatory and inhibitory (E/I) neurotransmission, especially in the prefrontal cortex and the amygdala, may underlie their etiopathology. In order to understand better the neurobiological bases of these alterations, we studied the impact of altered neurodevelopment and chronic early-life stress on these two brain regions...
March 2017: ENeuro
https://www.readbyqxmd.com/read/28460620/cx-4945-a-selective-inhibitor-of-casein-kinase-2-synergizes-with-b-cell-receptor-signaling-inhibitors-in-inducing-diffuse-large-b-cell-lymphoma-cell-death
#13
Elisa Mandato, Sara Canovas Nunes, Fortunato Zaffino, Alessandro Casellato, Paolo Macaccaro, Laura Quotti Tubi, Andrea Visentin, Livio Trentin, Gianpietro Semenzato, Francesco Piazza
BACKGROUND: Approximately one third of Diffuse Large B cell Lymphomas (DLBCL) are refractory or relapse. Novel therapeutic approaches under scrutiny include inhibitors of B-cell receptor (BCR) signaling. Protein kinase CK2 propels survival, proliferation and stress response in solid and hematologic malignancies and promotes a "non-oncogene addiction" phenotype. Whether this kinase regulates BCR signaling thus being a suitable pharmacological target in DLBCL is unknown. OBJECTIVE: To establish if CK2 controls DLBCL cell survival and the BCR signaling; to check if the combination of CK2 inhibitor CX-4945 and BCR blockers Ibrutinib and Fostamatinib is more effectively cytotoxic for DLBCL cells than the single agents; to survey the changes in signaling molecules downstream BCR upon CK2 inhibition...
April 26, 2017: Current Cancer Drug Targets
https://www.readbyqxmd.com/read/28424078/interleukin-6-displays-lung-anti-inflammatory-properties-and-exerts-protective-hemodynamic-effects-in-a-double-hit-murine-acute-lung-injury
#14
Guillaume Voiriot, Keyvan Razazi, Valérie Amsellem, Jeanne Tran Van Nhieu, Shariq Abid, Serge Adnot, Armand Mekontso Dessap, Bernard Maitre
BACKGROUND: Interleukin 6 (IL-6) is a predictive factor of poor prognosis in patients with acute respiratory distress syndrome (ARDS). However, its acute pulmonary hemodynamic effects and role in lung injury have not been investigated in a clinically relevant murine model of ARDS. METHODS: We used adult C57Bl6 wild-type (WT) and IL-6 knock-out (IL-6KO) mice. The animals received intravenous recombinant human IL-6 (rHuIL-6) or vehicle followed by intratracheal lipopolysaccharide (LPS) or saline before undergoing low tidal volume mechanical ventilation (MV) for 5 h...
April 19, 2017: Respiratory Research
https://www.readbyqxmd.com/read/28416758/synergistic-interactions-between-plk1-and-hdac-inhibitors-in-non-hodgkin-s-lymphoma-cells-occur-in-vitro-and-in-vivo-and-proceed-through-multiple-mechanisms
#15
Tri Nguyen, Rebecca Parker, Elisa Hawkins, Beata Holkova, Victor Yazbeck, Akhil Kolluri, Maciej Kmieciak, Mohamed Rahmani, Steven Grant
Interactions between the polo-like kinase 1 (PLK1) inhibitor volasertib and the histone deacetylase inhibitor (HDACI) belinostat were examined in diffuse large B-cell lymphoma (DLBCL) and mantle cell lymphoma (MCL) cells in vitro and in vivo. Exposure of DLBCL cells to very low concentrations of volasertib in combination with belinostat synergistically increased cell death (apoptosis). Similar interactions occurred in GC-, ABC-, double-hit DLBCL cells, MCL cells, bortezomib-resistant cells and primary lymphoma cells...
May 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28400483/somatic-and-inherited-mutations-in-primary-aldosteronism
#16
Fabio Luiz Fernandes-Rosa, Sheerazed Boulkroun, Maria-Christina Zennaro
Primary aldosteronism (PA), the most common form of secondary hypertension, is caused in the majority of cases by unilateral aldosterone producing adenoma (APA) or bilateral adrenal hyperplasia. In the last years, recurrent somatic mutations in KCNJ5, CACNA1D, ATP1A1, and ATP2B3 were proved to be associated with APA development, explaining more than 50% of sporadic APA. The identification of these mutations have allowed the establishment of a model for APA development involving modifications in the intracellular ionic equilibrium and in the regulation of cell membrane potential, leading to autonomous aldosterone overproduction...
April 11, 2017: Journal of Molecular Endocrinology
https://www.readbyqxmd.com/read/28398499/outcome-of-elderly-patients-with-diffuse-large-b-cell-lymphoma-treated-with-r-chop-results-from-the-uk-ncri-r-chop14v21-trial-with-combined-analysis-of-molecular-characteristics-with-the-dshnhl-ricover-60-trial
#17
A Kühnl, D Cunningham, N Counsell, E A Hawkes, W Qian, P Smith, N Chadwick, A Lawrie, P Mouncey, A Jack, C Pocock, K M Ardeshna, J Radford, A McMillan, J Davies, D Turner, A Kruger, P Johnson, J Gambell, A Rosenwald, G Ott, H Horn, M Ziepert, M Pfreundschuh, D Linch
BACKGROUND: There is an on-going debate whether 2- or 3-weekly administration of R-CHOP is the preferred first-line treatment for elderly patients with diffuse large B-cell lymphoma (DLBCL). The UK NCRI R-CHOP14v21 randomized phase 3 trial did not demonstrate a difference in outcomes between R-CHOP-14 and R-CHOP-21 in newly diagnosed DLBCL patients aged 19-88 years, but data on elderly patients have not been reported in detail so far. Here, we provide a subgroup analysis of patients ≥60 years treated on the R-CHOP14v21 trial with extended follow-up...
April 7, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28382141/overexpression-of-myc-and-bcl2-predicts-poor-prognosis-in-patients-with-extranodal-nk-t-cell-lymphoma-nasal-type
#18
Jing-Hua Wang, Xi-Wen Bi, Peng-Fei Li, Zhong-Jun Xia, Hui-Qiang Huang, Wen-Qi Jiang, Yu-Jing Zhang, Liang Wang
Background: Recently double-hit lymphoma or double protein expressor lymphoma has been identified as a distinct group of diffuse large B cell lymphoma with poor prognosis. However, the expression status, clinical and prognostic effect of combined overexpression of MYC and BCL2 in extranodal NK/T-cell lymphoma, nasal type (ENKTL) are not known. Materials and methods: Paraffin-embedded lymphoma samples from 53 patients with newly diagnosed ENKTL were studied using immunohistochemistry for MYC and BCL2, and fluorescent in situ hybridization (FISH) for MYC and BCL2 were done on 5 tissue sections with highest percentages of both MYC and BCL2 positive lymphoma cells...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28379189/the-role-of-c-myc-in-b-cell-lymphomas-diagnostic-and-molecular-aspects
#19
REVIEW
Lynh Nguyen, Peter Papenhausen, Haipeng Shao
c-MYC is one of the most essential transcriptional factors, regulating a diverse array of cellular functions, including proliferation, growth, and apoptosis. Dysregulation of c-MYC is essential in the pathogenesis of a number of B-cell lymphomas, but is rarely reported in T-cell lymphomas. c-MYC dysregulation induces lymphomagenesis by loss of the tight control of c-MYC expression, leading to overexpression of intact c-MYC protein, in contrast to the somatic mutations or fusion proteins seen in many other oncogenes...
April 5, 2017: Genes
https://www.readbyqxmd.com/read/28357165/persistent-afebrile-abdominal-pain-an-unusual-case-of-segmental-colitis-in-an-immunocompromised-host
#20
Ilias P Papakonstantinou, Emmanuel A Andreadis
In this report we describe a case of a 66-year-old woman who presented with right upper quadrant abdominal pain and bloody diarrhea. A workup revealed immunodeficiency, an immunologic profile with low complement levels resembling systemic lupus erythematosus, and a circumferential colonic wall lesion located in the ascending colon. After endoscopy and biopsy, the mass lesion was attributed to "double hit" diffuse large B-cell lymphoma, categorized as high grade large B-cell non-Hodgkin lymphoma according to the most recent revised 2016 World Health Organisation classification and considered to be a rare and highly aggressive tumor...
February 16, 2017: Curēus
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