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https://www.readbyqxmd.com/read/28730642/myc-expression-and-translocation-analyses-in-low-grade-and-transformed-follicular-lymphoma
#1
S M Aukema, R van Pel, I Nagel, S Bens, R Siebert, S Rosati, E van den Berg, A G Bosga-Bouwer, R E Kibbelaar, M Hoogendoorn, G W van Imhoff, J C Kluin-Nelemans, P M Kluin, M Nijland
Low grade follicular lymphoma (FL1/2) has an annual risk of transformation of approximately 3% which is associated with aberrations in CDKN2A/B, TP53 and MYC. Like in DLBCL high MYC expression in transformed FL (tFL) might predict a MYC breakpoint. We quantified MYC expression by immunohistochemistry and digital analysis in 41 paired biopsies from 20 patients with FL1/2 with subsequent transformation and in 4 isolated biopsies of tFL. As controls 28 biopsies of FL1/2 without transformation (median follow up 105 months) and 9 FL3A/B were analyzed...
July 21, 2017: Histopathology
https://www.readbyqxmd.com/read/28712322/is-now-the-time-for-molecular-driven-therapy-for-diffuse-large-b-cell-lymphoma
#2
Alice Di Rocco, Federico De Angelis, Michela Ansuinelli, Robin Foà, Maurizio Martelli
Recent genetic and molecular discoveries regarding alterations in diffuse large B-cell lymphoma (DLBCL) deeply changed the approach to this lymphoproliferative disorder. Novel additional predictors of outcomes and new therapeutic strategies are being introduced to improve outcomes. Areas covered: This review aims to analyse the recent molecular discoveries in DLBCL, the rationale of novel molecular driven treatments and their impact on DLBCL prognosis, especially in ABC-DLBCL and High Grade B Cell Lymphoma...
July 17, 2017: Expert Review of Hematology
https://www.readbyqxmd.com/read/28711572/emerging-strategies-in-treating-double-hit-lymphomas
#3
REVIEW
Chadi Nabhan, Anthony R Mato
Double hit lymphomas (DHLs) are a new category in the World Health Organization newest classification for lymphoid malignancies. DHL encompasses various histologies of lymphomas where the MYC oncogene and either BCL2 or BCL6 oncogenes are present concomitantly. Several observational studies and retrospective series have demonstrated that patients with DHL carry a poor prognosis and respond less and for a shorter duration to standard R-CHOP (rituximab, cyclophosphamide, vincristine, adriamycin, and prednisone)...
June 21, 2017: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/28676373/middle-age-exacerbates-acute-respiratory-distress-syndrome-in-a-double-hit-murine-model
#4
Guillaume Voiriot, Damien Contou, Jeanne Tran Van Nhieu, Valerie Amsellem, Elisabeth Marcos, Mehdi Latiri, Serge Adnot, Bernard Maitre, Armand Mekontso Dessap
RATIONALE: In a recent systematic review, aging has been identified as the only factor independently associated with mortality during human acute respiratory distress syndrome (ARDS). We explored this age-dependent severity in a clinically relevant double hit murine ARDS model. METHODS: Young adult (Y, 10-12weeks) and middle-old (O, 12-13months) male C57BL6 mice underwent an aspiration of Escherichia coli lipopolysaccharide (LPS) or control saline vehicle. Twenty hours later, four groups of mice were sacrificed [Y(control), O(control), Y(LPS) and O(LPS)]...
July 1, 2017: Experimental Gerontology
https://www.readbyqxmd.com/read/28654673/double-hit-of-nemo-gene-in-preeclampsia
#5
Agata Sakowicz, Tadeusz Pietrucha, Magda Rybak-Krzyszkowska, Hubert Huras, Agnieszka Gach, Bartosz Sakowicz, Mateusz Banaszczyk, Mariusz Grzesiak, Lidia Biesiada
The precise etiology of preeclampsia is unknown. Family studies indicate that both genetic and environmental factors influence its development. One of these factors is NFkB, whose activation depends on NEMO (NFkB essential modulator. This is the first study to investigate the association between the existence of single nucleotide variant of the NEMO gene and the appearance of preeclampsia. A total of 151 women (72 preeclamptic women and 79 controls) and their children were examined. Sanger sequencing was performed to identify variants in the NEMO gene in the preeclamptic mothers...
2017: PloS One
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
#6
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
#7
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
#8
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
#9
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
#10
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
#11
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
#12
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
#13
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
#14
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
#15
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
#16
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...
July 10, 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
#17
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
#18
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
#19
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
#20
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
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