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https://www.readbyqxmd.com/read/28340283/comparative-analysis-of-pulmonary-hypertension-in-patients-treated-with-imatinib-nilotinib-and-dasatinib
#1
Mariko Minami, Takeshi Arita, Hiromi Iwasaki, Tsuyoshi Muta, Takatoshi Aoki, Kenichi Aoki, Satoshi Yamasaki, Takamitsu Matsushima, Koji Kato, Katsuto Takenaka, Kazuki Tanimoto, Tomohiko Kamimura, Ryosuke Ogawa, Koichi Akashi, Toshihiro Miyamoto
Pulmonary hypertension (PH) is a rare, but life-threatening, adverse event in patients treated with tyrosine kinase inhibitors (TKIs), such as dasatinib, but has not been fully evaluated in patients treated with imatinib or nilotinib. We used echocardiography to noninvasively assess the incidence of PH in 105 patients with chronic myeloid leukaemia (CML) treated with imatinib (n = 37), nilotinib (n = 30) or dasatinib (n = 38). The mean triscupid regurgitation peak gradient (TRPG), which reflects pulmonary arterial pressure, was 22·7 mmHg in the imatinib group, 23·1 mmHg in the nilotinib group and 23·4 mmHg for dasatinib group...
March 24, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28340282/carfilzomib-induces-leukaemia-cell-apoptosis-via-inhibiting-elk1-kiaa1524-elk-1-cip2a-and-activating-pp2a-not-related-to-proteasome-inhibition
#2
Chun-Yu Liu, Feng-Shu Hsieh, Pei-Yi Chu, Wen-Chun Tsai, Chun-Teng Huang, Yuan-Bin Yu, Tzu-Ting Huang, Po-Shen Ko, Man-Hsin Hung, Wan-Lun Wang, Chung-Wai Shiau, Kuen-Feng Chen
Enhancing the tumour suppressive activity of protein phosphatase 2A (PP2A) has been suggested to be an anti-leukaemic strategy. KIAA1524 (also termed CIP2A), an oncoprotein inhibiting PP2A, is associated with disease progression in chronic myeloid leukaemia and may be prognostic in cytogenetically normal acute myeloid leukaemia. Here we demonstrated that the selective proteasome inhibitor, carfilzomib, induced apoptosis in sensitive primary leukaemia cells and in sensitive leukaemia cell lines, associated with KIAA1524 protein downregulation, increased PP2A activity and decreased p-Akt, but not with the proteasome inhibition effect of carfilzomib...
March 24, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28340281/high-ten-year-remission-rates-following-rituximab-fludarabine-mitoxantrone-and-dexamethasone-r-fnd-with-interferon-maintenance-in-indolent-lymphoma-results-of-a-randomized-study
#3
Loretta J Nastoupil, Peter McLaughlin, Lei Feng, Sattva S Neelapu, Felipe Samaniego, Fredrick B Hagemeister, Ana Ayala, Jorge E Romaguera, Andre H Goy, Eleanor Neal, Michael Wang, Luis Fayad, Michelle A Fanale, Yasuhiro Oki, Jason R Westin, Maria A Rodriguez, Fernando Cabanillas, Nathan H Fowler
We report a single-centre, randomized study evaluating the efficacy and safety of concurrent fludarabine, mitoxantrone, dexamethasone (FND) and rituximab versus sequential FND followed by rituximab in 158 patients with advanced stage, previously untreated indolent lymphoma, enrolled between 1997 and 2002. Patients were randomized to 6-8 cycles of FND followed by 6 monthly doses of rituximab or 6 doses of rituximab given concurrently with FND. All patients who achieved at least a partial response received 12 months of interferon (IFN) maintenance...
March 24, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28339935/nephrotoxicity-of-anticancer-treatment
#4
Jolanta Malyszko, Klaudia Kozlowska, Leszek Kozlowski, Jacek Malyszko
Severe adverse systemic drug events occur commonly as a result of treatment of cancer patients. Nephrotoxicity of chemotherapeutic agents remains a significant complication limiting the efficacy of the treatment. A variety of renal disease and electrolyte disorders can result from the drugs that are used to treat malignant disease. The kidneys are a major elimination pathway for many antineoplastic drugs and their metabolites. Tumour lysis syndrome, an emergency in haematooncology, occurs most often after the initiation of cytotoxic therapy in patients with high-grade lymphomas and acute lymphoblastic leukaemia...
October 6, 2016: Nephrology, Dialysis, Transplantation
https://www.readbyqxmd.com/read/28333259/predisposing-factors-and-outcome-of-uncommon-yeast-species-related-fungaemia-based-on-an-exhaustive-surveillance-programme-2002-14
#5
Stéphane Bretagne, Charlotte Renaudat, Marie Desnos-Ollivier, Karine Sitbon, Olivier Lortholary, Françoise Dromer
Objectives: Using registry data to compare fungaemia caused by uncommon yeast species (UYS; i.e. other than Candida albicans , Candida glabrata , Candida parapsilosis , Candida tropicalis and Candida krusei ) and C. albicans -related fungaemia can reveal specific predisposing factors of UYS with potential impact on treatment strategies. Methods: We analysed 338 episodes of UYS fungaemia prospectively collected from 27 hospitals (Paris, France; 1 October 2002-31 December 2014) and compared these with 1998 single episodes of C...
March 5, 2017: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/28333143/molecular-insights-of-gas6-tam-in-cancer-development-and-therapy
#6
REVIEW
Guiling Wu, Zhiqiang Ma, Wei Hu, Dongjin Wang, Bing Gong, Chongxi Fan, Shuai Jiang, Tian Li, Jianyuan Gao, Yang Yang
Since growth arrest-specific gene 6 (Gas6) was discovered in 1988, numerous studies have highlighted the role of the Gas6 protein and its receptors Tyro3, Axl and Mer (collectively referred to as TAM), in proliferation, apoptosis, efferocytosis, leukocyte migration, sequestration and platelet aggregation. Gas6 has a critical role in the development of multiple types of cancers, including pancreatic, prostate, oral, ovarian and renal cancers. Acute myelocytic leukaemia (AML) is a Gas6-dependent cancer, and Gas6 expression predicts poor prognosis in AML...
March 23, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28331814/molecular-techniques-for-the-personalised-management-of-patients-with-chronic-myeloid-leukaemia
#7
REVIEW
Mary Alikian, Robert Peter Gale, Jane F Apperley, Letizia Foroni
Chronic myeloid leukemia (CML) is the paradigm for targeted cancer therapy. RT-qPCR is the gold standard for monitoring response to tyrosine kinase-inhibitor (TKI) therapy based on the reduction of blood or bone marrow BCR-ABL1. Some patients with CML and very low or undetectable levels of BCR-ABL1 transcripts can stop TKI-therapy without CML recurrence. However, about 60 percent of patients discontinuing TKI-therapy have rapid leukaemia recurrence. This has increased the need for more sensitive and specific techniques to measure residual CML cells...
March 2017: Biomolecular Detection and Quantification
https://www.readbyqxmd.com/read/28331025/tetraploidy-acute-myeloid-leukaemia-after-chromosome-16-inversion
#8
Alba Sara Vilches, Aranzazu Díaz de Bustamante, Jorge Sanchez-Calero, María Teresa Darnaude
Our patient is a 36-year-old man referred by his general physician to the Department of Hematology because of mild neutropenia in a routine analysis at work. There was no history of previous diseases, and examination was normal. Blood investigations confirmed the neutropenia and showed elongation of prothrombin time. A bone marrow examination was performed revealing about 10% of myeloblasts on the aspirate smears. A cytogenetic study showed chromosome 16 inversion in all of these cells and tetraploidy only in some of them, which were extremely large in size...
March 22, 2017: BMJ Case Reports
https://www.readbyqxmd.com/read/28330607/association-between-anti-thymocyte-globulin-exposure-and-survival-outcomes-in-adult-unrelated-haemopoietic-cell-transplantation-a-multicentre-retrospective-pharmacodynamic-cohort-analysis
#9
Rick Admiraal, Stefan Nierkens, Moniek A de Witte, Eefke J Petersen, Ger-Jan Fleurke, Luka Verrest, Svetlana V Belitser, Robbert G M Bredius, Reinier A P Raymakers, Catherijne A J Knibbe, Monique C Minnema, Charlotte van Kesteren, Jurgen Kuball, Jaap J Boelens
BACKGROUND: Anti-thymocyte globulin (ATG) is used to prevent graft-versus-host disease (GvHD) after allogeneic haemopoietic cell transplantation (HCT). However, ATG can also cause delayed immune reconstitution of T cells, negatively affecting survival. We studied the relation between exposure to ATG and clinical outcomes in adult patients with acute leukaemia and myelodysplastic syndrome. METHODS: We did a retrospective, pharmacokinetic-pharmacodynamic analysis of data from patients with acute lymphoid leukaemia, acute myeloid leukaemia, or myelodysplastic syndrome receiving their first T-cell repleted allogeneic peripheral blood stem cell HCT with ATG (thymoglobulin) as part of non-myeloablative conditioning from March 1, 2004, to June 1, 2015...
March 16, 2017: Lancet Haematology
https://www.readbyqxmd.com/read/28330312/isolation-and-screening-of-l-asparaginase-free-of-glutaminase-and-urease-from-fungal-sp
#10
Kruthi Doriya, Devarai Santhosh Kumar
L-Asparaginase is a chemotherapeutic drug used in the treatment of acute lymphoblastic leukaemia (ALL), a malignant disorder in children. L-Asparaginase helps in removing acrylamide found in fried and baked foods that is carcinogenic in nature. L-Asparaginase is present in plants, animals and microbes. Various microorganisms such as bacteria, yeast and fungi are generally used for the production of L-asparaginase as it is difficult to obtain the same from plants and animals. L-Asparaginase from bacteria causes anaphylaxis and other abnormal sensitive reactions due to low specificity to asparagine...
December 2016: 3 Biotech
https://www.readbyqxmd.com/read/28329763/the-allosteric-inhibitor-abl001-enables-dual-targeting-of-bcr-abl1
#11
Andrew A Wylie, Joseph Schoepfer, Wolfgang Jahnke, Sandra W Cowan-Jacob, Alice Loo, Pascal Furet, Andreas L Marzinzik, Xavier Pelle, Jerry Donovan, Wenjing Zhu, Silvia Buonamici, A Quamrul Hassan, Franco Lombardo, Varsha Iyer, Michael Palmer, Giuliano Berellini, Stephanie Dodd, Sanjeev Thohan, Hans Bitter, Susan Branford, David M Ross, Timothy P Hughes, Lilli Petruzzelli, K Gary Vanasse, Markus Warmuth, Francesco Hofmann, Nicholas J Keen, William R Sellers
Chronic myeloid leukaemia (CML) is driven by the activity of the BCR-ABL1 fusion oncoprotein. ABL1 kinase inhibitors have improved the clinical outcomes for patients with CML, with over 80% of patients treated with imatinib surviving for more than 10 years. Second-generation ABL1 kinase inhibitors induce more potent molecular responses in both previously untreated and imatinib-resistant patients with CML. Studies in patients with chronic-phase CML have shown that around 50% of patients who achieve and maintain undetectable BCR-ABL1 transcript levels for at least 2 years remain disease-free after the withdrawal of treatment...
March 22, 2017: Nature
https://www.readbyqxmd.com/read/28326171/large-scale-isolation-and-cytotoxicity-of-extracellular-vesicles-derived-from-activated-human-natural-killer-cells
#12
Ambrose Y Jong, Chun-Hua Wu, Jingbo Li, Jianping Sun, Muller Fabbri, Alan S Wayne, Robert C Seeger
Extracellular vesicles (EVs) have been the focus of great interest, as they appear to be involved in numerous important cellular processes. They deliver bioactive macromolecules such as proteins, lipids, and nucleic acids, allowing intercellular communication in multicellular organisms. EVs are secreted by all cell types, including immune cells such as natural killer cells (NK), and they may play important roles in the immune system. Currently, a large-scale procedure to obtain functional NK EVs is lacking, limiting their use clinically...
2017: Journal of Extracellular Vesicles
https://www.readbyqxmd.com/read/28324282/recurrent-bowel-blood-translocations-of-escherichia-coli-with-the-unique-virulence-characteristics-over-three-year-period-in-the-patient-with-acute-myeloid-leukaemia-case-report
#13
Beata Krawczyk, Anna Śledzińska, Agnieszka Piekarska, Andrzej Hellmann, Józef Kur
In patients with haematological malignancies, the bowel remains the main source of Escherichia coli bloodstream infections. We present the clinical example of recurrent bowel-blood translocations of E. coli with the unique virulence characteristics in a 55-year-old male with the diagnosis of acute myeloid leukaemia. The virulent factors profile of examined strains confirmed that the co-existence of genes papC, sfa, usp and cnf1, encoding virulence factors, predisposes E. coli to translocation from the gastrointestinal tract to the vascular bed...
March 21, 2017: Journal of Applied Genetics
https://www.readbyqxmd.com/read/28322129/including-historical-data-in-the-analysis-of-clinical-trials-is-it-worth-the-effort
#14
Joost van Rosmalen, David Dejardin, Yvette van Norden, Bob Löwenberg, Emmanuel Lesaffre
Data of previous trials with a similar setting are often available in the analysis of clinical trials. Several Bayesian methods have been proposed for including historical data as prior information in the analysis of the current trial, such as the (modified) power prior, the (robust) meta-analytic-predictive prior, the commensurate prior and methods proposed by Pocock and Murray et al. We compared these methods and illustrated their use in a practical setting, including an assessment of the comparability of the current and the historical data...
January 1, 2017: Statistical Methods in Medical Research
https://www.readbyqxmd.com/read/28320453/dysregulated-systemic-lymphocytes-affect-the-balance-of-osteogenic-adipogenic-differentiation-of-bone-mesenchymal-stem-cells-after-local-irradiation
#15
Xiaoya Xu, Ruixia Li, Yi Zhou, Qiong Zou, Qiaoling Ding, Jinfeng Wang, Weifang Jin, Guoqiang Hua, Jianjun Gao
BACKGROUND: While it is known that irradiation can induce local and systemic bone loss over time, how focal irradiation induces systemic bone complications remains unclear. Immune cells are thought to be crucial to bone homeostasis, and abnormal immune cells lead to serious disruption of bone homeostasis, such as in acute lymphoblastic leukaemia. This disruption primarily occurs due to inhibition of the osteogenic differentiation of bone mesenchymal stem cells (BMSCs). METHODS: In this study, we detected local and systemic bone loss in trabecular bone by micro-computed tomography (micro-CT) and measurement of peroxisome proliferator-activated receptor gamma (PPARγ) and runt-related transcription factor 2 (RUNX2) expression in BMSCs using real-time polymerase chain reaction and western blotting...
March 20, 2017: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/28319909/stability-and-change-in-disease-prestige-a-comparative-analysis-of-three-surveys-spanning-a-quarter-of-a-century
#16
Dag Album, Lars E F Johannessen, Erik B Rasmussen
In this paper, we present a comparative analysis of three survey studies of disease prestige in medical culture. The studies were conducted in 1990, 2002 and 2014 using the same research design. In each of the three rounds, a sample of Norwegian physicians was asked to rate a set of 38 diseases on a scale from 1 to 9 according to the prestige they believed health personnel in general would award them. The results show a remarkable stability in the prestige rank order over 25 years. The top three diseases in all three surveys were leukaemia, brain tumour and myocardial infarction...
March 14, 2017: Social Science & Medicine
https://www.readbyqxmd.com/read/28318761/the-bone-marrow-microenvironment-home-of-the-leukemic-blasts
#17
REVIEW
Manar S Shafat, Bruno Gnaneswaran, Kristian M Bowles, Stuart A Rushworth
Acute Myeloid Leukaemia (AML) is a genetically, biologically and clinically heterogeneous set of diseases, which are characterised by an increased growth of abnormal myeloid progenitor cells within the bone marrow (BM). Ex-vivo AML exhibits a high level of spontaneous apoptosis. Furthermore, relapse for patients achieving remission occurs from minimal residual disease harboured within the BM microenvironment. Taken together, these observations illustrate the importance of the BM microenvironment in sustaining AML...
March 12, 2017: Blood Reviews
https://www.readbyqxmd.com/read/28304148/the-enigmatic-role-of-runx1-in-female-related-cancers-current-knowledge-future-perspectives
#18
REVIEW
Alessandra I Riggio, Karen Blyth
Historically associated with the aetiology of human leukaemia, the RUNX1 gene has in recent years reared its head in an assortment of epithelial cancers. This review discusses the state-of-the-art knowledge of the enigmatic role played by RUNX1 in female-related cancers of the breast, the uterus and the ovary. The weight of evidence accumulated so far is indicative of a very context-dependent role, as either an oncogene or a tumour suppressor. This is corroborated by high-throughput sequencing endeavours which report different genetic alterations affecting the gene, including amplification, deep deletion and mutations...
March 17, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28303898/circulating-tumour-dna-reflects-treatment-response-and-clonal-evolution-in-chronic-lymphocytic-leukaemia
#19
Paul Yeh, Tane Hunter, Devbarna Sinha, Sarah Ftouni, Elise Wallach, Damian Jiang, Yih-Chih Chan, Stephen Q Wong, Maria Joao Silva, Ravikiran Vedururu, Kenneth Doig, Enid Lam, Gisela Mir Arnau, Timothy Semple, Meaghan Wall, Andjelija Zivanovic, Rishu Agarwal, Pasquale Petrone, Kate Jones, David Westerman, Piers Blombery, John F Seymour, Anthony T Papenfuss, Mark A Dawson, Constantine S Tam, Sarah-Jane Dawson
Several novel therapeutics are poised to change the natural history of chronic lymphocytic leukaemia (CLL) and the increasing use of these therapies has highlighted limitations of traditional disease monitoring methods. Here we demonstrate that circulating tumour DNA (ctDNA) is readily detectable in patients with CLL. Importantly, ctDNA does not simply mirror the genomic information contained within circulating malignant lymphocytes but instead parallels changes across different disease compartments following treatment with novel therapies...
March 17, 2017: Nature Communications
https://www.readbyqxmd.com/read/28303892/how-good-are-we-at-predicting-the-fate-of-someone-with-acute-myeloid-leukaemia
#20
EDITORIAL
E Estey, R P Gale
No abstract text is available yet for this article.
March 17, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
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