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https://www.readbyqxmd.com/read/29675840/outcome-of-children-with-newly-diagnosed-acute-lymphoblastic-leukemia-treated-with-cclg-all-2008-the-first-nation-wide-prospective-multicenter-study-in-china
#1
Lei Cui, Zhi-Gang Li, Yi-Huan Chai, Jie Yu, Ju Gao, Xiao-Fan Zhu, Run-Ming Jin, Xiao-Dong Shi, Le-Ping Zhang, Yi-Jin Gao, Rui-Dong Zhang, Hu-Yong Zheng, Shao-Yan Hu, Ying-Hui Cui, Yi-Ping Zhu, Yao Zou, Margaret Hl Ng, Yan Xiao, Jun-Hui Li, Yong-Hong Zhang, Hai-Long He, Ying Xian, Tian-You Wang, Chi-Kong Li, Min-Yuan Wu
Acute lymphoblastic leukemia (ALL) is the most common malignancy among children. The trial Chinese Children Leukemia Group (CCLG)-ALL 2008 was a prospective clinical trial designed to improve treatment outcome of childhood ALL through the first nation-wide collaborative study in China. Totally 2231 patients were recruited from ten tertiary hospitals in eight cities. The patients were stratified according to clinical-biological characteristics and early treatment response. Standard risk (SR) and intermediate risk (IR) groups were treated with a modified BFM based protocol, and there was 25-50% dose reduction during intensification phases in the SR group...
April 20, 2018: American Journal of Hematology
https://www.readbyqxmd.com/read/29674345/quantitative-interaction-analysis-permits-molecular-insights-into-functional-nox4-nadph-oxidase-heterodimer-assembly
#2
Sharon O'Neill, Magalie Mathis, Lidija Kovacic, Suisheng Zhang, Juergen Reinhardt, Dimitri Scholz, Ulrich Schopfer, Rochdi Bouhelal, Ulla G Knaus
Protein-protein interactions critically regulate many biological systems, but quantifying functional assembly of multi-pass membrane complexes in their native context is still challenging. Here, we combined modeling-assisted protein modification and information from human disease variants with a minimal-size fusion tag, split-luciferase-based approach to probe assembly of the NADPH oxidase 4 (NOX4)-p22phox enzyme, an integral membrane complex with unresolved structure, which is required for electron transfer and generation of reactive oxygen species (ROS)...
April 19, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29656333/interferon-%C3%AE-salvage-treatment-is-effective-for-patients-with-acute-leukemia-myelodysplastic-syndrome-with-unsatisfactory-response-to-minimal-residual-disease-directed-donor-lymphocyte-infusion-after-allogeneic-hematopoietic-stem-cell-transplantation
#3
Xiaodong Mo, Xiaohui Zhang, Lanping Xu, Yu Wang, Chenhua Yan, Huan Chen, Yuhong Chen, Wei Han, Fengrong Wang, Jingzhi Wang, Kaiyan Liu, Xiaojun Huang
The efficacy of salvage interferon-α (IFN-α) treatment was investigated in patients with unsatisfactory response to minimal residual disease (MRD)-directed donor lymphocyte infusion (DLI) (n = 24). Patients who did not become MRD-negative at 1 month after DLI were those with unsatisfactory response and were eligible to receive salvage IFN-α treatment within 3 months of DLI. Recombinant human IFN-α-2b injections were subcutaneously administered 2-3 times a week for 6 months. Nine (37.5%), 6 (25.0%), and 3 (12...
April 14, 2018: Frontiers of Medicine
https://www.readbyqxmd.com/read/29643105/a-next-generation-sequencing-based-assay-for-minimal-residual-disease-assessment-in-aml-patients-with-flt3-itd-mutations
#4
Mark J Levis, Alexander E Perl, Jessica K Altman, Christopher D Gocke, Erkut Bahceci, Jason Hill, Chaofeng Liu, Zhiyi Xie, Andrew R Carson, Valerie McClain, Timothy T Stenzel, Jeffrey E Miller
Internal tandem duplications in fms-like tyrosine kinase 3 ( FLT3- ITDs) are common in acute myeloid leukemia (AML) and confer a poor prognosis. A sensitive and specific assay for the detection of minimal residual disease (MRD) in FLT3- ITD mutated AML could guide therapy decisions. Existing assays for MRD in FLT3- ITD AML have not been particularly useful because of limited sensitivity. We developed a sensitive and specific MRD assay for FLT3- ITD mutations using next-generation sequencing. The initial validation of this assay was performed by spiking fixed amounts of mutant DNA into wild-type DNA to establish a sensitivity of detection equivalent to ≥1 FLT3- ITD-containing cell in 10 000, with a minimum input of 100 000 cell equivalents of DNA...
April 24, 2018: Blood Advances
https://www.readbyqxmd.com/read/29630051/flow-cytometry-to-estimate-leukemia-stem-cells-in-primary-acute-myeloid-leukemia-and-in-patient-derived-xenografts-at-diagnosis-and-follow-up
#5
Thomas Boyer, Fanny Gonzales, Adriana Plesa, Pauline Peyrouze, Adeline Barthelemy, Soizic Guihard, Bruno Quesnel, Christophe Roumier, Claude Preudhomme, Meyling Cheok
Acute myeloid leukemia (AML) is a heterogeneous, and if not treated, fatal disease. It is the most common cause of leukemia-associated mortality in adults. Initially, AML is a disease of hematopoietic stem cells (HSC) characterized by arrest of differentiation, subsequent accumulation of leukemia blast cells, and reduced production of functional hematopoietic elements. Heterogeneity extends to the presence of leukemia stem cells (LSC), with this dynamic cell compartment evolving to overcome various selection pressures imposed upon during leukemia progression and treatment...
March 26, 2018: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/29629252/prevention-efforts-for-malaria
#6
REVIEW
Tinashe A Tizifa, Alinune N Kabaghe, Robert S McCann, Henk van den Berg, Michele Van Vugt, Kamija S Phiri
Purpose of Review: Malaria remains a global burden contributing to morbidity and mortality especially in children under 5 years of age. Despite the progress achieved towards malaria burden reduction, achieving elimination in more countries remains a challenge. This article aims to review the prevention and control strategies for malaria, to assess their impact towards reducing the disease burden and to highlight the best practices observed. Recent Findings: Use of long-lasting insecticide-treated nets and indoor residual spraying has resulted a decline in the incidence and prevalence of malaria in Sub-Saharan Africa...
2018: Current Tropical Medicine Reports
https://www.readbyqxmd.com/read/29627246/robustness-and-sensitivity-of-a-blueprint-for-on-farm-estimation-of-dairy-cow-energy-balance
#7
Vivi M Thorup, Mizeck G G Chagunda, Amelie Fischer, Martin R Weisbjerg, Nicolas C Friggens
Excessive negative energy balance (EB) has been associated with decreased reproductive performance and increased risk of lameness and metabolic diseases. On-farm, automated EB estimates for individual cows would enable dairy farmers to detect excessive negative EB early and act to minimize its extent and duration by altering feeding. Previously, we have shown that EB can be estimated from frequent measurements of body weight (BW) and body condition score (BCS) changes, referred to as EBbody . In this study, we investigated the robustness and sensitivity of the EBbody method to assess its genericity and on-farm applicability...
April 4, 2018: Journal of Dairy Science
https://www.readbyqxmd.com/read/29625246/droplet-digital-pcr-is-a-robust-tool-for-monitoring-minimal-residual-disease-in-adult-philadelphia-positive-acute-lymphoblastic-leukemia
#8
Nicoletta Coccaro, Luisa Anelli, Antonella Zagaria, Paola Casieri, Giuseppina Tota, Paola Orsini, Luciana Impera, Angela Minervini, Crescenzio F Minervini, Cosimo Cumbo, Elisa Parciante, Paola Carluccio, Claudia Brunetti, Giorgina Specchia, Francesco Albano
The BCR-ABL1 p190 fusion transcript (m-bcr) is the most frequent variant observed in Philadelphia-positive (Ph+) acute lymphoblastic leukemia (ALL). Qualitative-PCR and real-time quantitative PCR are the currently used methods to monitor minimal residual disease (MRD) in Ph+ ALL patients; for the latter, full standardization and an international quality validation are lacking. Here, we developed a droplet digital PCR (ddPCR) assay for MRD monitoring in p190+ ALL cases. The analytical performance was assessed by the limit of detection determination, demonstrating a reliability, sensitivity, and precision of the assay of up to 0...
April 3, 2018: Journal of Molecular Diagnostics: JMD
https://www.readbyqxmd.com/read/29624462/minimal-residual-disease-testing-after-induction-chemotherapy-for-acute-myeloid-leukemia-moving-beyond-prognostication
#9
Roland B Walter
No abstract text is available yet for this article.
April 6, 2018: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/29608548/reassessment-of-the-risk-stratified-gd-2008-all-protocol
#10
Li-Ping Que, Ke Huang, Jian-Pei Fang, Hong-Gui Xu, Dun-Hua Zhou, Yang Li, Lv-Hong Xu, Jian Li, Hai-Lei Chen
OBJECTIVE: To explore the clinical features and outcomes of relapsed childhood acute lymphoblastic leukemia (ALL) at our center, achieve the early detection of risk factors for recurrence and assess the risk-stratified Guangdong (GD)-2008 ALL protocol. MATERIALS AND METHODS: In total, 59 Chinese childhood ALL patients treated with the GD-2008 ALL protocol who relapsed between July 2008 and March 2015 were enrolled in this study. Their clinical features and outcomes were retrospectively analyzed and compared with those of 218 patients who achieved continuous complete remission...
March 30, 2018: Journal of Pediatric Hematology/oncology
https://www.readbyqxmd.com/read/29606109/neoadjuvant-degarelix-with-or-without-apalutamide-followed-by-radical-prostatectomy-for-intermediate-and-high-risk-prostate-cancer-arneo-a-randomized-double-blind-placebo-controlled-trial
#11
Lorenzo Tosco, Annouschka Laenen, Thomas Gevaert, Isabelle Salmon, Christine Decaestecker, Elai Davicioni, Christine Buerki, Frank Claessens, Johan Swinnen, Karolien Goffin, Raymond Oyen, Wouter Everaerts, Lisa Moris, Gert De Meerleer, Karin Haustermans, Steven Joniau
BACKGROUND: Recent retrospective data suggest that neoadjuvant androgen deprivation therapy can improve the prognosis of high-risk prostate cancer (PCa) patients. Novel androgen receptor pathway inhibitors are nowadays available for treatment of metastatic PCa and these compounds are promising for early stage disease. Apalutamide is a pure androgen antagonist with a very high affinity with the androgen receptor. The combination of apalutamide with degarelix, an LHRH antagonist, could increase the efficacy compared to degarelix alone...
April 2, 2018: BMC Cancer
https://www.readbyqxmd.com/read/29605436/the-role-of-za-channel-water-mediated-interactions-in-the-design-of-bromodomain-selective-bet-inhibitors
#12
Nagakumar Bharatham, Peter J Slavish, Brandon M Young, Anang A Shelat
The Bromodomain and Extra-Terminal domain (BET) family of proteins are involved in the regulation of gene transcription, and their dysregulation is implicated in several diseases including cancer. BET proteins contain two tandem bromodomains (BD1 and BD2) that independently recognize acetylated-lysine residues and appear to have distinct biological roles. We compared several published co-crystal structures and found five positions near the substrate binding pocket that vary between BET bromodomains. One position located in the ZA loop has unique properties...
March 22, 2018: Journal of Molecular Graphics & Modelling
https://www.readbyqxmd.com/read/29603593/phase-i-trial-of-the-mtor-inhibitor-everolimus-in-combination-with-multi-agent-chemotherapy-in-relapsed-childhood-acute-lymphoblastic-leukemia
#13
Andrew E Place, Yana Pikman, Kristen E Stevenson, Marian H Harris, Melinda Pauly, Maria-Luisa Sulis, Nobuko Hijiya, Lia Gore, Todd M Cooper, Mignon L Loh, Giovanni Roti, Donna S Neuberg, Sarah K Hunt, Sarah Orloff-Parry, Kimberly Stegmaier, Stephen E Sallan, Lewis B Silverman
BACKGROUND: We sought to determine the feasibility of co-administering everolimus with a four-drug reinduction in children and adolescents with acute lymphoblastic leukemia (ALL) experiencing a first marrow relapse. PROCEDURE: This phase I study tested everolimus with vincristine, prednisone, pegaspargase and doxorubicin in patients with marrow relapse occurring >18 months after first complete remission (CR). The primary aim was to identify the maximum tolerated dose of everolimus...
March 30, 2018: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/29603591/phase-i-study-of-vorinostat-in-combination-with-isotretinoin-in-patients-with-refractory-recurrent-neuroblastoma-a-new-approaches-to-neuroblastoma-therapy-nant-trial
#14
Navin Pinto, Steven G DuBois, Araz Marachelian, Scott J Diede, Agne Taraseviciute, Julia L Glade Bender, Denice Tsao-Wei, Susan G Groshen, Joel M Reid, Daphne A Haas-Kogan, C Patrick Reynolds, Min H Kang, Meredith S Irwin, Margaret E Macy, Judith G Villablanca, Katherine K Matthay, Julie R Park
BACKGROUND: Vorinostat combined with retinoids produces additive antitumor effects in preclinical studies of neuroblastoma. Higher systemic exposures of vorinostat than achieved in pediatric phase I trials with continuous daily dosing are necessary for in vivo increased histone acetylation and cytotoxic activity. We conducted a phase I trial in children with relapsed/refractory neuroblastoma to determine the maximum tolerated dose (MTD) of vorinostat on an interrupted schedule, escalating beyond the previously identified pediatric MTD...
March 30, 2018: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/29601269/molecular-minimal-residual-disease-in-acute-myeloid-leukemia
#15
Mojca Jongen-Lavrencic, Tim Grob, Diana Hanekamp, François G Kavelaars, Adil Al Hinai, Annelieke Zeilemaker, Claudia A J Erpelinck-Verschueren, Patrycja L Gradowska, Rosa Meijer, Jacqueline Cloos, Bart J Biemond, Carlos Graux, Marinus van Marwijk Kooy, Markus G Manz, Thomas Pabst, Jakob R Passweg, Violaine Havelange, Gert J Ossenkoppele, Mathijs A Sanders, Gerrit J Schuurhuis, Bob Löwenberg, Peter J M Valk
BACKGROUND: Patients with acute myeloid leukemia (AML) often reach complete remission, but relapse rates remain high. Next-generation sequencing enables the detection of molecular minimal residual disease in virtually every patient, but its clinical value for the prediction of relapse has yet to be established. METHODS: We conducted a study involving patients 18 to 65 years of age who had newly diagnosed AML. Targeted next-generation sequencing was carried out at diagnosis and after induction therapy (during complete remission)...
March 29, 2018: New England Journal of Medicine
https://www.readbyqxmd.com/read/29601212/measurable-residual-disease-at-induction-redefines-partial-response-in-acute-myeloid-leukemia-and-stratifies-outcomes-in-patients-at-standard-risk-without-npm1-mutations
#16
Sylvie D Freeman, Robert K Hills, Paul Virgo, Naeem Khan, Steve Couzens, Richard Dillon, Amanda Gilkes, Laura Upton, Ove Juul Nielsen, James D Cavenagh, Gail Jones, Asim Khwaja, Paul Cahalin, Ian Thomas, David Grimwade, Alan K Burnett, Nigel H Russell
Purpose We investigated the effect on outcome of measurable or minimal residual disease (MRD) status after each induction course to evaluate the extent of its predictive value for acute myeloid leukemia (AML) risk groups, including NPM1 wild-type (wt) standard risk, when incorporated with other induction response criteria. Methods As part of the NCRI AML17 trial, 2,450 younger adult patients with AML or high-risk myelodysplastic syndrome had prospective multiparameter flow cytometric MRD (MFC-MRD) assessment...
March 30, 2018: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/29595004/-mechanisms-and-implications-of-cancer-cell-dormancy-in-head-and-neck-carcinoma
#17
Gao Xiaolei, Liang Xinhua, Tang Yaling
Disease metastasis and relapse in many cancer patients several years (even decades) after surgical remission have been recently acknowledged as cases of cancer dormancy. Although cases of minimal residual disease are well documented, knowledge on its biological mechanisms and clinical implications remains limited. To date, numerous reviews have summarized the three potential models that may explain this phenomenon, including the angiogenic, immunologic, and cellular dormancy. In this study, we discuss newly uncovered mechanisms governing tumor cell dormancy in head and neck cancer, emphasizing on the crosstalk between dormant tumor cells and their microenvironments...
February 1, 2018: Hua Xi Kou Qiang Yi Xue za Zhi, Huaxi Kouqiang Yixue Zazhi, West China Journal of Stomatology
https://www.readbyqxmd.com/read/29590547/ibrutinib-plus-venetoclax-for-the-treatment-of-mantle-cell-lymphoma
#18
COMPARATIVE STUDY
Constantine S Tam, Mary Ann Anderson, Christiane Pott, Rishu Agarwal, Sasanka Handunnetti, Rodney J Hicks, Kate Burbury, Gillian Turner, Juliana Di Iulio, Mathias Bressel, David Westerman, Stephen Lade, Martin Dreyling, Sarah-Jane Dawson, Mark A Dawson, John F Seymour, Andrew W Roberts
BACKGROUND: Both the BTK inhibitor ibrutinib and the BCL2 inhibitor venetoclax are active as monotherapy in the treatment of mantle-cell lymphoma. Complete response rates of 21% have been observed for each agent when administered as long-term continuous therapy. Preclinical models predict synergy in combination. METHODS: We conducted a single-group, phase 2 study of daily oral ibrutinib and venetoclax in patients, as compared with historical controls. Patients commenced ibrutinib monotherapy at a dose of 560 mg per day...
March 29, 2018: New England Journal of Medicine
https://www.readbyqxmd.com/read/29588374/flow-cytometric-minimal-residual-disease-assessment-of-peripheral-blood-in-acute-lymphoblastic-leukaemia-patients-has-potential-for-early-detection-of-relapsed-extramedullary-disease
#19
Alissa Keegan, Karry Charest, Ryan Schmidt, Debra Briggs, Daniel J Deangelo, Betty Li, Elizabeth A Morgan, Olga Pozdnyakova
OBJECTIVES: To evaluate peripheral blood (PB) for minimal residual disease (MRD) assessment in adults with acute lymphoblastic leukaemia (ALL). METHODS: We analysed 76 matched bone marrow (BM) aspirate and PB specimens independently for the presence of ALL MRD by six-colour flow cytometry (FC). RESULTS: The overall rate of BM MRD-positivity was 24% (18/76) and PB was also MRD-positive in 22% (4/18) of BM-positive cases. We identified two cases with evidence of leukaemic cells in PB at the time of the extramedullary relapse that were interpreted as MRD-negative in BM...
March 27, 2018: Journal of Clinical Pathology
https://www.readbyqxmd.com/read/29580435/cell-free-dna-as-a-post-treatment-surveillance-strategy-current-status
#20
REVIEW
Justin M Burgener, Ariana Rostami, Daniel D De Carvalho, Scott V Bratman
Circulating tumor DNA (ctDNA) consists of cell-free DNA (cfDNA) fragments that are released from tumor cells into the bloodstream. ctDNA harbors cancer-specific genetic and epigenetic alterations that allow its detection and quantification using a variety of emerging techniques. The promise of convenient non-invasive access to the complex and dynamic molecular features of cancer through peripheral blood has galvanized translational researchers around this topic with compelling routes to clinical implementation, particularly in the post-treatment surveillance setting...
October 2017: Seminars in Oncology
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