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Cell free DNA lymphoma

Alex F Herrera, Haesook T Kim, Katherine A Kong, Malek Faham, Heather Sun, Aliyah R Sohani, Edwin P Alyea, Victoria E Carlton, Yi-Bin Chen, Corey S Cutler, Vincent T Ho, John Koreth, Chitra Kotwaliwale, Sarah Nikiforow, Jerome Ritz, Scott J Rodig, Robert J Soiffer, Joseph H Antin, Philippe Armand
Next-generation sequencing (NGS)-based circulating tumour DNA (ctDNA) detection is a promising monitoring tool for lymphoid malignancies. We evaluated whether the presence of ctDNA was associated with outcome after allogeneic haematopoietic stem cell transplantation (HSCT) in lymphoma patients. We studied 88 patients drawn from a phase 3 clinical trial of reduced-intensity conditioning HSCT in lymphoma. Conventional restaging and collection of peripheral blood samples occurred at pre-specified time points before and after HSCT and were assayed for ctDNA by sequencing of the immunoglobulin or T-cell receptor genes...
October 6, 2016: British Journal of Haematology
Staci L Haney, G Michael Upchurch, Jana Opavska, David Klinkebiel, Ryan A Hlady, Sohini Roy, Samikshan Dutta, Kaustubh Datta, Rene Opavsky
DNA methyltransferase 3A (DNMT3A) is an enzyme involved in DNA methylation that is frequently mutated in human hematologic malignancies. We have previously shown that inactivation of Dnmt3a in hematopoietic cells results in chronic lymphocytic leukemia in mice. Here we show that 12% of Dnmt3a-deficient mice develop CD8+ mature peripheral T cell lymphomas (PTCL) and 29% of mice are affected by both diseases. 10% of Dnmt3a+/- mice develop lymphomas, suggesting that Dnmt3a is a haploinsufficient tumor suppressor in PTCL...
September 2016: PLoS Genetics
Lasse Sommer Kristensen, Jakob Werner Hansen, Søren Sommer Kristensen, Dorte Tholstrup, Laurine Bente Schram Harsløf, Ole Birger Pedersen, Peter De Nully Brown, Kirsten Grønbæk
BACKGROUND: The prognostic value of aberrant DNA methylation of cell-free circulating DNA in plasma has not previously been evaluated in diffuse large B cell lymphoma (DLBCL). The aim of this study was to investigate if aberrant promoter DNA methylation can be detected in plasma from DLBCL patients and to evaluate this as a prognostic marker. Furthermore, we wanted to follow possible changes in methylation levels during treatment. Seventy-four patients were enrolled in the study, of which 59 received rituximab and CHOP-like chemotherapy...
2016: Clinical Epigenetics
Christopher Melani, Mark Roschewski
The ability to precisely monitor the effectiveness of therapy for non-Hodgkin lymphoma has important clinical implications. In patients with curable lymphomas, such as diffuse large B-cell lymphoma, the eradication of all disease is necessary for cure. In patients with incurable lymphomas, such as follicular lymphoma and mantle cell lymphoma, deep and durable remissions are associated with improvements in survival. Radiographic imaging modalities such as computed tomography and positron emission tomography are the current gold standard for monitoring therapy, but they are fundamentally limited by radiation risks, costs, lack of tumor specificity, and inability to detect disease at the molecular level...
August 2016: Oncology (Williston Park, NY)
Na-Na Lou, Xu-Chao Zhang, Hua-Jun Chen, Qing Zhou, Li-Xu Yan, Zhi Xie, Jian Su, Zhi-Hong Chen, Hai-Yan Tu, Hong-Hong Yan, Zhen Wang, Chong-Rui Xu, Ben-Yuan Jiang, Bin-Chao Wang, Xiao-Yan Bai, Wen-Zhao Zhong, Yi-Long Wu, Jin-Ji Yang
The co-occurrence of epidermal growth factor receptor (EGFR) mutations and anaplastic lymphoma kinase (ALK) rearrangements constitutes a rare molecular subtype of non-small-cell lung cancer (NSCLC). Herein, we assessed the clinical outcomes and incidence of acquired resistance to tyrosine kinase inhibitors (TKIs) in this subtype. So we enrolled 118 advanced NSCLC treated with TKIs. EGFR mutations and ALK rearrangements were detected by DNA sequencing or Scorpion amplification refractory mutation system and fluorescence in situ hybridization respectively...
August 11, 2016: Oncotarget
Bradley M Haverkos, Alejandro A Gru, Susan M Geyer, Anissa K Bingman, Jessica A Hemminger, Anjali Mishra, Henry K Wong, Preeti Pancholi, Aharon G Freud, Michael A Caligiuri, Robert A Baiocchi, Pierluigi Porcu
INTRODUCTION: Outcomes in advanced stage (AS) cutaneous T-cell lymphomas (CTCL) are poor but with great variability. Epstein-Barr virus (EBV) is associated with a subset of non-Hodgkin lymphomas. Frequency of plasma EBV-DNA (pEBVd) detection, concordance with EBV RNA (EBER) in tumor tissue, codetection of plasma cytomegalovirus DNA (pCMVd), and prognostic effect in AS CTCL are unknown. PATIENTS AND METHODS: Patients (n = 46; 2006-2013) with AS CTCL (≥IIB) were retrospectively studied...
August 2016: Clinical Lymphoma, Myeloma & Leukemia
Andishe Attarbaschi, Elisa Carraro, Oussama Abla, Shlomit Barzilai-Birenboim, Simon Bomken, Laurence Brugieres, Eva Bubanska, Birgit Burkhardt, Alan Ks Chiang, Monika Csoka, Alina Fedorova, Janez Jazbec, Edita Kabickova, Zdenka Krenova, Jelena Lazic, Jan Loeffen, Georg Mann, Felix Niggli, Natasha Miakova, Tomoo Osumi, Leila Ronceray, Anne Uyttebroeck, Denise Williams, Wilhelm Woessmann, Grazyna Wrobel, Marta Pillon
Children and adolescents with pre-existing conditions such as DNA repair defects or other primary immunodeficiencies have an increased risk of non-Hodgkin's lymphoma. However, large-scale data on patients with non-Hodgkin's lymphoma and their entire spectrum of pre-existing conditions are scarce. In a retrospective multi-national study performed by means of questionnaires sent out to the national study groups or centres, the two largest consortia in childhood non-Hodgkin's lymphoma, the European Intergroup for Childhood non-Hodgkin's lymphoma and the international Berlin-Frankfurt-Munster Study Group, identified 213 patients with non-Hodgkin's lymphoma and a pre-existing condition...
August 11, 2016: Haematologica
Vincent Camus, Aspasia Stamatoullas, Sylvain Mareschal, Pierre-Julien Viailly, Nasrin Sarafan-Vasseur, Elodie Bohers, Sydney Dubois, Jean Michel Picquenot, Philippe Ruminy, Catherine Maingonnat, Philippe Bertrand, Marie Cornic, Valérie Tallon-Simon, Stéphanie Becker, Liana Veresezan, Thierry Frebourg, Pierre Vera, Christian Bastard, Hervé Tilly, Fabrice Jardin
Classical Hodgkin lymphoma is one of the most common lymphomas and shares clinical and genetic features with primary mediastinal B-cell lymphoma. In this retrospective study, we analyzed the recurrent hotspot mutation of the exportin 1 (XPO1, p.E571K) gene, previously identified in primary mediastinal B-cell lymphoma, in biopsies and plasma circulating cell-free DNA from patients with classical Hodgkin lymphoma using a highly sensitive digital PCR technique. A total of 94 patients were included in the present study...
September 2016: Haematologica
Yasuhito Tanaka
Hepatitis B virus (HBV) and hepatitis C virus (HCV), discovered as causative viruses of post-transfusion hepatitis, become persistent infections, leading to chronic hepatitis, cirrhosis, and hepatocellular carcinoma (HCC). For HCV, recent IFN-free direct-acting antiviral (DAA) therapies have increased sustained virological response (SVR) rates and reduced adverse events. IFN-based therapies, still the standard of care in Asian countries, are influenced by IL28B genetic variants and the liver fibrosis stage, but the DAA combinations obscure the influence of these factors...
February 2016: Rinsho Byori. the Japanese Journal of Clinical Pathology
Yago Nieto, Benigno C Valdez, Peter F Thall, Roy B Jones, Wei Wei, Alan Myers, Chitra Hosing, Sairah Ahmed, Uday Popat, Elizabeth J Shpall, Muzaffar Qazilbash, Alison Gulbis, Paolo Anderlini, Nina Shah, Qaiser Bashir, Amin Alousi, Yasuhiro Oki, Michelle Fanale, Bouthaina Dabaja, Chelsea Pinnix, Richard Champlin, Borje S Andersson
BACKGROUND: More active high-dose chemotherapy (HDC) regimens are needed for refractory lymphomas. The authors previously combined infusional gemcitabine with busulfan and melphalan (Gem/Bu/Mel) pursuing DNA damage repair inhibition. Subsequently, they combined Gem/Bu/Mel with vorinostat, which facilitates chemotherapy access to DNA. The resulting regimen was safe and synergistic. However, vorinostat induced DNA methyltransferase up-regulation, which could be preclinically abrogated by azacitidine, increasing tumor-cell kill...
September 1, 2016: Cancer
Alison M Betts, Nahor Haddish-Berhane, John Tolsma, Paul Jasper, Lindsay E King, Yongliang Sun, Subramanyam Chakrapani, Boris Shor, Joseph Boni, Theodore R Johnson
A mechanism-based pharmacokinetic/pharmacodynamic (PK/PD) model was used for preclinical to clinical translation of inotuzumab ozogamicin, a CD22-targeting antibody-drug conjugate (ADC) for B cell malignancies including non-Hodgkin's lymphoma (NHL) and acute lymphocytic leukemia (ALL). Preclinical data was integrated in a PK/PD model which included (1) a plasma PK model characterizing disposition and clearance of inotuzumab ozogamicin and its released payload N-Ac-γ-calicheamicin DMH, (2) a tumor disposition model describing ADC diffusion into the tumor extracellular environment, (3) a cellular model describing inotuzumab ozogamicin binding to CD22, internalization, intracellular N-Ac-γ-calicheamicin DMH release, binding to DNA, or efflux from the tumor cell, and (4) tumor growth and inhibition in mouse xenograft models...
September 2016: AAPS Journal
Paola Bordi, Marzia Del Re, Marcello Tiseo
No abstract text is available yet for this article.
May 5, 2016: New England Journal of Medicine
Alice T Shaw, Jeffrey A Engelman
No abstract text is available yet for this article.
May 5, 2016: New England Journal of Medicine
Helga D Munch-Petersen, Fazila Asmar, Konstantinos Dimopoulos, Aušrinė Areškevičiūtė, Peter Brown, Mia Seremet Girkov, Anja Pedersen, Lene D Sjö, Steffen Heegaard, Helle Broholm, Lasse S Kristensen, Elisabeth Ralfkiaer, Kirsten Grønbæk
Primary central nervous system lymphoma (PCNSL) is an aggressive variant of diffuse large B-cell lymphoma (DLBCL) confined to the CNS. TP53 mutations (MUT-TP53) were investigated in the context of MIR34A/B/C- and DAPK promoter methylation status, and associated with clinical outcomes in PCNSL patients. In a total of 107 PCNSL patients clinical data were recorded, histopathology reassessed, and genetic and epigenetic aberrations of the p53-miR34-DAPK network studied. TP53 mutational status (exon 5-8), with structural classification of single nucleotide variations according to the IARC-TP53-Database, methylation status of MIR34A/B/C and DAPK, and p53-protein expression were assessed...
2016: Acta Neuropathologica Communications
Paras Jawaid, Mati Ur Rehman, Mariame Ali Hassan, Qing Li Zhao, Peng Li, Yusei Miyamoto, Masaki Misawa, Ryohei Ogawa, Tadamichi Shimizu, Takashi Kondo
In this study, we report on the potential use of platinum nanoparticles (Pt-NPs), a superoxide dismutase (SOD)/catalase mimetic antioxidant, in combination with 1MHz ultrasound (US) at an intensity of 0.4 W/cm(2), 10% duty factor, 100 Hz PRF, for 2 min. Apoptosis induction was assessed by DNA fragmentation assay, cell cycle analysis and Annexin V-FITC/PI staining. Cell killing was confirmed by cell counting and microscopic examination. The mitochondrial and Ca(2+)-dependent pathways were investigated. Caspase-8 expression and autophagy-related proteins were detected by spectrophotometry and western blot analysis, respectively...
July 2016: Ultrasonics Sonochemistry
Simona Primerano, Roberta Burnelli, Elisa Carraro, Marta Pillon, Caterina Elia, Piero Farruggia, Alessandra Sala, Luciana Vinti, Salvatore Buffardi, Giuseppe Basso, Maurizio Mascarin, Lara Mussolin
Levels of plasma cell-free DNA (cfDNA) of a large series of children with classical Hodgkin lymphoma (cHL) were evaluated and analyzed at diagnosis and during chemotherapy treatment in relation with clinical characteristics. CfDNA levels in cHL patients were significantly higher compared with controls (p=0.002). CfDNA at diagnosis was correlated with presence of B symptoms (p=0.027) and high erythrocyte sedimentation rate (p=0.049). We found that the increasing of plasma cfDNA after first chemotherapy cycle seems to be associated with a worse prognosis (p=0...
2016: Journal of Cancer
Rong Liang, Zhe Wang, Qing-Xian Bai, Guang-Xun Gao, Lan Yang, Tao Zhang, Hong-Tao Gu, Bao-Xia Dong, Mi-Mi Shu, Cai-Xia Hao, Na Zhang, Xie-Qun Chen
BACKGROUND: Extranodal natural killer (NK)/T cell lymphoma (ENKTL) is an aggressive non-Hodgkin's lymphoma with high mortality and poor prognosis despite radiotherapy and chemotherapy. The current analysis aimed to assess the pathological features, clinical features, and prognostic indicators of ENKTL. MATERIAL AND METHODS: 120 ENKTL patients were analyzed for pathologic diagnosis and clinical disease manifestations from April 2007 to October 2012. Complete remission, 2-year overall survival, and progression-free survival were analyzed...
2016: Oncology Research and Treatment
Vincent Camus, Nasrin Sarafan-Vasseur, Elodie Bohers, Sydney Dubois, Sylvain Mareschal, Philippe Bertrand, Pierre-Julien Viailly, Philippe Ruminy, Catherine Maingonnat, Emilie Lemasle, Aspasia Stamatoullas, Jean-Michel Picquenot, Marie Cornic, Ludivine Beaussire, Christian Bastard, Thierry Frebourg, Hervé Tilly, Fabrice Jardin
Diffuse large B-cell lymphoma (DLBCL) is an aggressive and heterogeneous malignancy harboring frequent targetable activating somatic mutations. Emerging evidence suggests that circulating cell-free DNA (cfDNA) can be used to detect somatic variants in DLBCL using Next-Generation Sequencing (NGS) experiments. In this proof-of-concept study, we chose to develop simple and valuable digital PCR (dPCR) assays for the detection of recurrent exportin-1 (XPO1) E571K, EZH2 Y641N, and MYD88 L265P mutations in DLBCL patients, thereby identifying patients most likely to potentially benefit from targeted therapies...
September 2016: Leukemia & Lymphoma
Keiji Shinozuka, Hongwei Tang, Roy B Jones, Donghui Li, Yago Nieto
The goal of this study was to determine whether single nucleotide polymorphisms (SNPs) in genes involved in gemcitabine metabolism, DNA damage repair, multidrug resistance, and alkylator detoxification influence the clinical outcome of patients with refractory/relapsed lymphoid malignancies receiving high-dose gemcitabine/busulfan/melphalan (Gem/Bu/Mel) with autologous stem cell support. We evaluated 21 germline SNPs of the gemcitabine metabolism genes CDA, deoxycytidine kinase, and hCNT3; DNA damage repair genes RECQL, X-ray repair complementing 1, RAD54L, ATM, ATR, MLH1, MSH2, MSH3, TREX1, EXO1, and TP73; and multidrug-resistance genes MRP2 and MRP5; as well as glutathione-S-transferase GSTP1 in 153 patients with relapsed or refractory lymphoma or myeloma receiving Gem/Bu/Mel...
May 2016: Biology of Blood and Marrow Transplantation
Seok Jin Kim, Joon Young Choi, Seung Hyup Hyun, Chang-Seok Ki, Dongryul Oh, Yong Chan Ahn, Young Hyeh Ko, Sunkyu Choi, Sin-Ho Jung, Pek-Lan Khong, Tiffany Tang, Xuexian Yan, Soon Thye Lim, Yok-Lam Kwong, Won Seog Kim
BACKGROUND: Assessment of tumour viability after treatment is essential for prediction of treatment failure in patients with extranodal natural killer/T-cell lymphoma (ENKTL). We aimed to assess the use of the post-treatment Deauville score on PET-CT and Epstein-Barr virus DNA as a predictor of residual tumour, to establish the risk of treatment failure in patients with newly diagnosed ENKTL. METHODS: In a retrospective analysis of patient data we assessed the prognostic relevance of the Deauville score (five-point scale) on PET-CT and circulating Epstein-Barr virus DNA after completion of treatment in consecutive patients with ENKTL who met eligibility criteria (newly diagnosed and received non-anthracycline-based chemotherapy, concurrent chemoradiotherapy, or both together) diagnosed at the Samsung Medical Center in Seoul, South Korea...
February 2015: Lancet Haematology
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