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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/28728785/operative-strategies-to-reduce-cerebral-embolic-events-during-on-and-off-pump-coronary-artery-bypass-surgery-a-stratified-prospective-randomized-trial
#2
Michael E Halkos, Aaron Anderson, Jose Nilo G Binongo, Anthony Stringer, Yi Lasanajak, Vinod H Thourani, Omar M Lattouf, Robert A Guyton, Kim T Baio, Eric Sarin, William B Keeling, N Renee Cook, Katherine Carssow, Alexis Neill, Kathryn E Glas, John D Puskas
OBJECTIVE: To determine the impact of different aortic clamping strategies on the incidence of cerebral embolic events during coronary artery bypass grafting (CABG). METHODS: Between 2012 and 2015, 142 patients with low-grade aortic disease (epiaortic ultrasound grade I/II) undergoing primary isolated CABG were studied. Those undergoing off-pump CABG were randomized to a partial clamp (n = 36) or clampless facilitating device (CFD; n = 36) strategy. Those undergoing on-pump CABG were randomized to a single-clamp (n = 34) or double-clamp (n = 36) strategy...
June 16, 2017: Journal of Thoracic and Cardiovascular Surgery
https://www.readbyqxmd.com/read/28712322/is-now-the-time-for-molecular-driven-therapy-for-diffuse-large-b-cell-lymphoma
#3
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
#4
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/28695462/transgenic-mice-overexpressing-the-divalent-metal-transporter-1-exhibit-iron-accumulation-and-enhanced-parkin-expression-in-the-brain
#5
Cheng-Wu Zhang, Yee Kit Tai, Bing-Han Chai, Katherine C M Chew, Eng-Tat Ang, Fai Tsang, Bryce W Q Tan, Eugenia T E Hong, Abu Bakar Ali Asad, Kai-Hsiang Chuang, Kah-Leong Lim, Tuck Wah Soong
Exposure to divalent metals such as iron and manganese is thought to increase the risk for Parkinson's disease (PD). Under normal circumstances, cellular iron and manganese uptake is regulated by the divalent metal transporter 1 (DMT1). Accordingly, alterations in DMT1 levels may underlie the abnormal accumulation of metal ions and thereby disease pathogenesis. Here, we have generated transgenic mice overexpressing DMT1 under the direction of a mouse prion promoter and demonstrated its robust expression in several regions of the brain...
July 10, 2017: Neuromolecular Medicine
https://www.readbyqxmd.com/read/28688450/alignment-orientation-and-coulomb-explosion-of-difluoroiodobenzene-studied-with-the-pixel-imaging-mass-spectrometry-pimms-camera
#6
Kasra Amini, Rebecca Boll, Alexandra Lauer, Michael Burt, Jason W L Lee, Lauge Christensen, Felix Brauβe, Terence Mullins, Evgeny Savelyev, Utuq Ablikim, Nora Berrah, Cédric Bomme, Stefan Düsterer, Benjamin Erk, Hauke Höppner, Per Johnsson, Thomas Kierspel, Faruk Krecinic, Jochen Küpper, Maria Müller, Erland Müller, Harald Redlin, Arnaud Rouzée, Nora Schirmel, Jan Thøgersen, Simone Techert, Sven Toleikis, Rolf Treusch, Sebastian Trippel, Anatoli Ulmer, Joss Wiese, Claire Vallance, Artem Rudenko, Henrik Stapelfeldt, Mark Brouard, Daniel Rolles
Laser-induced adiabatic alignment and mixed-field orientation of 2,6-difluoroiodobenzene (C6H3F2I) molecules are probed by Coulomb explosion imaging following either near-infrared strong-field ionization or extreme-ultraviolet multi-photon inner-shell ionization using free-electron laser pulses. The resulting photoelectrons and fragment ions are captured by a double-sided velocity map imaging spectrometer and projected onto two position-sensitive detectors. The ion side of the spectrometer is equipped with a pixel imaging mass spectrometry camera, a time-stamping pixelated detector that can record the hit positions and arrival times of up to four ions per pixel per acquisition cycle...
July 7, 2017: Journal of Chemical Physics
https://www.readbyqxmd.com/read/28676373/middle-age-exacerbates-acute-respiratory-distress-syndrome-in-a-double-hit-murine-model
#7
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
#8
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/28618395/erg-overexpression-plus-slc45a3-prostein-and-pten-expression-loss-strong-association-of-the-triple-hit-phenotype-with-an-aggressive-pathway-of-prostate-cancer-progression
#9
Silvia Hernández-Llodrà, Nuria Juanpere, Silvia de Muga, Marta Lorenzo, Joan Gil, Alba Font-Tello, Laia Agell, Raquel Albero-González, Laura Segalés, José Merino, Laia Serrano, Lluís Fumadó, Lluís Cecchini, Josep Lloreta Trull
TMPRSS2 and SLC45A3 rearrangements may coexist in the same tumor. ERG rearrangements and PTEN loss are concomitant events in prostate cancer (PrCa), and can cooperate in progression. We have reported that mRNA expression of TMPRSS2-ERG and SLC45A3-ERG rearrangements plus PTEN loss define an aggressive tumor subset. The aim of this study has been to validate these results by immunohistochemistry in a large cohort of tumors. ERG, SLC45A3 and PTEN immunostaining and their association with pathological features and PSA progression-free survival were analyzed in 220 PrCa (PSMAR-Biobank, Barcelona, Spain)...
May 26, 2017: Oncotarget
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
#10
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/28614202/further-exploration-of-the-complexities-of-large-b-cell-lymphomas-with-myc-abnormalities-and-the-importance-of-a-blastoid-morphology
#11
Erika M Moore, Nidhi Aggarwal, Urvashi Surti, Steven H Swerdlow
The 2016 World Health Organization classification recognized "high-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements" (double/triple-hit lymphoma [DTHL]) and "high-grade B-cell lymphoma, not otherwise specified," which includes non-DTHL with a "blastoid" or "intermediate" cytology. Although extensively studied, many questions remain, including which cases belong in these categories, which factors mitigate their adverse prognosis, and when to perform fluorescence in situ hybridization studies...
June 13, 2017: American Journal of Surgical Pathology
https://www.readbyqxmd.com/read/28602556/attacks-against-health-care-in-syria-2015-16-results-from-a-real-time-reporting-tool
#12
Mohamed Elamein, Hilary Bower, Camilo Valderrama, Daher Zedan, Hazem Rihawi, Khaled Almilaji, Mohammed Abdelhafeez, Nabil Tabbal, Naser Almhawish, Sophie Maes, Alaa AbouZeid
BACKGROUND: Collecting credible data on violence against health services, health workers, and patients in war zones is a massive challenge, but crucial to understanding the extent to which international humanitarian law is being breached. We describe a new system used mainly in areas of Syria with a substantial presence of armed opposition groups since November, 2015, to detect and verify attacks on health-care services and describe their effect. METHODS: All Turkey health cluster organisations with a physical presence in Syria, either through deployed and locally employed staff, were asked to participate in the Monitoring Violence against Health Care (MVH) alert network...
June 7, 2017: Lancet
https://www.readbyqxmd.com/read/28600333/how-i-treat-double-hit-lymphoma
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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/28577310/elucidating-the-molecular-basis-of-msh2-deficient-tumors-by-combined-germline-and-somatic-analysis
#19
Gardenia M Vargas-Parra, Maribel González-Acosta, Bryony A Thompson, Carolina Gómez, Anna Fernández, Estela Dámaso, Tirso Pons, Monika Morak, Jesús Del Valle, Silvia Iglesias, Àngela Velasco, Ares Solanes, Xavier Sanjuan, Natàlia Padilla, Xavier de la Cruz, Alfonso Valencia, Elke Holinki-Feder, Joan Brunet, Lídia Feliubadaló, Conxi Lázaro, Matilde Navarro, Marta Pineda, Gabriel Capellá
In a proportion of patients presenting mismatch repair (MMR)-deficient tumors, no germline MMR mutations are identified, the so-called Lynch-like syndrome (LLS). Recently, MMR-deficient tumors have been associated with germline mutations in POLE and MUTYH or double somatic MMR events. Our aim was to elucidate the molecular basis of MSH2-deficient LS-suspected cases using a comprehensive analysis of colorectal cancer (CRC)-associated genes at germline and somatic level. Fifty-eight probands harboring MSH2-deficient tumors were included...
June 2, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28535287/a-flow-cytometry-based-screen-identifies-mbnl1-modulators-that-rescue-splicing-defects-in-myotonic-dystrophy-type-i
#20
Fan Zhang, Nicole E Bodycombe, Keith M Haskell, Yumei L Sun, Eric T Wang, Carl A Morris, Lyn H Jones, Lauren D Wood, Mathew T Pletcher
Myotonic Dystrophy Type 1 (DM1) is a rare genetic disease caused by expansion of CTG trinucleotide repeats ((CTG)exp) in the 3' untranslated region of the DMPK gene. The repeat transcripts sequester the RNA binding protein Muscleblind-like protein 1 (MBNL1) and hamper its normal function in pre-mRNA splicing. Overexpressing exogenous MBNL1 in the DM1 mouse model has been shown to rescue the splicing defects and reverse myotonia. Although a viable therapeutic strategy, pharmacological modulators of MBNL1 expression have not been identified...
May 23, 2017: Human Molecular Genetics
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