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https://www.readbyqxmd.com/read/28209616/octn1-is-a-high-affinity-carrier-of-nucleoside-analogs
#1
Christina Drenberg, Alice A Gibson, Stanley Pounds, Lei Shi, Dena Rhinehart, Lie Li, Shuiying Hu, Guoqing Du, Anne T Nies, Matthias Schwab, Navjotsingh Pabla, William Blum, Tanja A Gruber, Sharyn D Baker, Alex Sparreboom
Resistance to xenobiotic nucleosides used to treat acute myeloid leukemia (AML) and other cancers remains a major obstacle to clinical management. One process suggested to participate in resistance is reduced uptake into tumor cells via nucleoside transporters, although precise mechanisms are not understood. Through transcriptomic profiling, we determined that low expression of the ergothioneine transporter OCTN1 (SLC22A4; ETT) strongly predicts poor event-free survival and overall survival in multiple cohorts of AML patients receiving treatment with the cytidine nucleoside analog cytarabine...
February 16, 2017: Cancer Research
https://www.readbyqxmd.com/read/28190862/acute-myeloid-leukemia-with-t-3-21-q13-q22-a-novel-simple-variant-of-the-21q22-runx1-translocation
#2
Yuka Tsuruoka, Hirotaka Sakai, Akiko Uchida, Yu Uemura, Kazuyuki Sato, Satoshi Yokoi, Yuji Nishio, Manabu Matsunawa, Yoshinori Suzuki, Yasushi Isobe, Masayuki Kato, Naoto Tomita, Yasuyuki Inoue, Ikuo Miura
A 69-year-old man diagnosed with leukocytosis was referred to our hospital in July 201X. The patient was diagnosed as having a myelodysplastic/myeloproliferative neoplasm. However, he presented with leukemia 2 months later. Chromosomal analysis of a bone marrow sample documented that this patient had a normal karyotype. The patient was successfully treated with idarubicin and cytarabine, and he underwent three courses of consolidation therapy. However, he suffered a relapse in May of the following year. A cytogenetic analysis revealed the presence of a t (3;21) (q13;q22) translocation, and fluorescence in situ hybridization of metaphase spreads detected three signals corresponding to the runt related transcription factor 1 (RUNX1) on the derivative chromosomes 3 and 21, besides the normal chromosome 21...
2017: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
https://www.readbyqxmd.com/read/28183623/the-role-of-nanoparticles-in-the-albumin-cytarabine-and-albumin-methotrexate-interactions
#3
Danuta Pentak, Małgorzata Maciążek-Jurczyk, Zygmunt H Zawada
Understanding the interactions which occur between nanomaterials and biomolecules is one of the most important issues in nanotechnology. Determining the properties of nanoparticles obtained through the use of novel methods and defining the scope of their application as drug carriers has important practical significance. Nanoparticles containing methotrexate and cytarabine obtained by a modified reverse-phase evaporation method (mREV) were characterized through the use of the UV/Vis and NMR methods. Obtained results confirmed high degree of analysed drugs encapsulation...
April 1, 2017: Materials Science & Engineering. C, Materials for Biological Applications
https://www.readbyqxmd.com/read/28179321/efficacy-and-toxicity-of-induction-therapy-with-cladribine-idarubicin-and-cytarabine-iac-for-acute-myeloid-leukemia
#4
Susan K Woelich, James T Braun, Martin W Schoen, Reshma Ramlal, Carl E Freter, Paul J Petruska, Jack M Lionberger
We report our single-center experience with cytarabine and idarubicin for induction therapy for acute myeloid leukemia (AML) with an additional 5 days of cladribine (IAC therapy). From July 2012 to September 2014, 38 patients completed a full course of IAC induction. Median patient age was 61 years, 61% of patients were ≥60 years old, and 71% were male. The complete remission (CR) rate was 63% following a single induction course, three patients (8%) required a second induction course to achieve CR, for an overall response rate of 71%...
2017: Anticancer Research
https://www.readbyqxmd.com/read/28178709/neoplastic-meningitis-due-to-lung-breast-and-melanoma-metastases
#5
Emilie Le Rhun, Sophie Taillibert, Marc C Chamberlain
BACKGROUND: Neoplastic meningitis, a central nervous system (CNS) complication of cancer metastatic to the meninges and cerebrospinal fluid (CSF), is relevant to oncologists due to the impact of the disease on patient quality of life and survival rates. METHODS: A review of the literature of articles published in English was conducted with regard to neoplastic meningitis. RESULTS: The incidence of neoplastic meningitis is increasing because patients with cancer are surviving longer in part because of the use of novel therapies with poor CNS penetration...
January 2017: Cancer Control: Journal of the Moffitt Cancer Center
https://www.readbyqxmd.com/read/28176818/mechanisms-responsible-for-the-synergistic-antileukemic-interactions-between-atr-inhibition-and-cytarabine-in-acute-myeloid-leukemia-cells
#6
Jun Ma, Xinyu Li, Yongwei Su, Jianyun Zhao, Daniel A Luedtke, Valeria Epshteyn, Holly Edwards, Guan Wang, Zhihong Wang, Roland Chu, Jeffrey W Taub, Hai Lin, Yue Wang, Yubin Ge
Acute myeloid leukemia (AML) continues to be a challenging disease to treat, thus new treatment strategies are needed. In this study, we investigated the antileukemic effects of ATR inhibition alone or combined with cytarabine in AML cells. Treatment with the ATR-selective inhibitor AZ20 caused proliferation inhibition in AML cell lines and primary patient samples. It partially abolished the G2 cell cycle checkpoint and caused DNA replication stress and damage, accompanied by CDK1-independent apoptosis and downregulation of RRM1 and RRM2...
February 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28171800/epigenetic-drug-combination-overcomes-osteoblast-induced-chemoprotection-in-pediatric-acute-lymphoid-leukemia
#7
Anthony Quagliano, Anilkumar Gopalakrishnapillai, Sonali P Barwe
Although there has been much progress in the treatment of acute lymphoblastic leukemia (ALL), decreased sensitivity to chemotherapy remains a significant issue. Recent studies have shown how interactions with the bone marrow microenvironment can protect ALL cells from chemotherapy and allow for the persistence of the disease. Epigenetic drugs have been used for the treatment of ALL, but there are no reports on whether these drugs can overcome bone marrow-induced chemoprotection. Our study investigates the ability of the DNA methyltransferase inhibitor azacitidine and the histone deacetylase inhibitor panobinostat to overcome chemoprotective effects mediated by osteoblasts...
January 27, 2017: Leukemia Research
https://www.readbyqxmd.com/read/28169005/nelarabine-associated-reversible-guillain-barr%C3%A3-like-syndrome-or-myelopathy-in-an-adult-patient-with-primary-refractory-t-lymphoblastic-lymphoma
#8
Chrysavgi Lalayanni, Eirini Baldoumi, Sotiris Papayiannopoulos, Konstantia Tziola, Riad Saloum, Achilles Anagnostopoulos
Nelarabine is a purine analogue used for the treatment of patients with relapsed or refractory T-cell acute lymphoblastic leukemia and T-cell lymphoblastic lymphoma mainly as a bridge to stem cell transplantation. The water-soluble prodrug of 9-beta-D-arabinofuranosyl guanine (Ara-G) is phosphorylated within leukemic cells to form ara-G triphosphate (ara-GTP), which terminates DNA chain elongation, resulting in cell death. The drug received accelerated approval by the US Food and Drug Administration (FDA) on October 2005 based on the induction of complete remissions in 2 phase II trials...
November 17, 2016: Current Problems in Cancer
https://www.readbyqxmd.com/read/28160570/resistance-of-leukemia-cells-to-cytarabine-chemotherapy-is-mediated-by-bone-marrow-stroma-involves-cell-surface-equilibrative-nucleoside-transporter-1-removal-and-correlates-with-patient-outcome
#9
Patricia Macanas-Pirard, Richard Broekhuizen, Alfonso González, Claudia Oyanadel, Daniel Ernst, Patricia García, Viviana P Montecinos, Felipe Court, Mauricio Ocqueteau, Pablo Ramirez, Bruno Nervi
The interaction between acute myeloid leukemia cells (AML) with the bone marrow stroma cells (BMSCs) determines a protective environment that favors tumor development and resistance to conventional chemotherapy. We showed that BMSCs secrete soluble factors that protect AML cells from Ara-C induced cytotoxicity. This leukemia chemoresistance is associated with a decrease in the equilibrative nucleoside transporter (ENT1) activity by inducing removal of ENT1 from the cell surface. Reduction of cell proliferation was also observed with activation of AKT and mTOR-dependent cell survival pathways, which may also contribute to the tumor chemoprotection...
February 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/28154969/what-is-the-best-daunorubicin-dose-and-schedule-for-acute-myeloid-leukemia-induction
#10
REVIEW
Priyanka Pophali, Mark Litzow
Daunorubicin dose intensification for induction in acute myeloid leukemia has been reported as an effective strategy in recent trials to improve patient outcomes without worsening treatment-related toxicity. Based on available evidence, 90 mg/m(2) of daunorubicin given for three consecutive days (cumulative dose 270 mg/m(2)) as a part of the "7 + 3" induction regimen along with cytarabine is the most effective dose to achieve a complete remission as well as improve survival in patients who can tolerate it...
January 2017: Current Treatment Options in Oncology
https://www.readbyqxmd.com/read/28148843/monkey-business-repurposing-a-protein-from-the-simian-immunodeficiency-virus-to-enhance-cytotoxic-chemotherapy
#11
Saar Gill
Cytarabine activity in acute myeloid leukemia blasts can be augmented by degrading the expression of a critical hydrolase.
February 1, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28146632/antibody-targeted-cyclodextrin-based-nanoparticles-for-sirna-delivery-in-the-treatment-of-acute-myeloid-leukemia-physicochemical-characteristics-in-vitro-mechanistic-studies-and-ex-vivo-patient-derived-therapeutic-efficacy
#12
Jianfeng Guo, Eileen G Russell, Raphael Darcy, Thomas G Cotter, Sharon L McKenna, Mary R Cahill, Caitriona M O'Driscoll
Acute myeloid leukemia (AML) is the most common type of acute leukemia in adults and is associated with high relapse rates. It is known that leukemia stem cells (LSCs), a very small subpopulation of the total number of leukemic cells, maintain the leukemia phenotype (∼80-90% of AML remain the same as at first diagnosis), display chemotherapy resistance, and contribute to disease regeneration. Therefore, targeting LSCs could control the relapse of AML. Small interfering RNA (siRNA), an effector of the RNA interference (RNAi) pathway, can selectively downregulate any gene implicated in the pathology of disease, presenting great potential for treatment of AML...
February 14, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28143954/early-treatment-intensification-with-r-ice-and-90y-ibritumomab-tiuxetan-zevalin-beam-stem-cell-transplantation-in-patients-with-high-risk-diffuse-large-b-cell-lymphoma-patients-and-positive-interim-pet-after-4-cycles-of-r-chop-14
#13
Mark Hertzberg, Maher K Gandhi, Judith Trotman, Belinda Butcher, John Taper, Amanda Johnston, Devinder Gill, Shir-Jing Ho, Gavin Cull, Keith Fay, Geoff Chong, Andrew Grigg, Ian D Lewis, Sam Milliken, William Renwick, Uwe Hahn, Robin Filshie, George Kannourakis, Anne-Marie Watson, Pauline Warburton, Andrew Wirth, John F Seymour, Michael S Hofman, Rodney J Hicks
In the treatment of diffuse large B-cell lymphoma, a persistently positive [(18)F]fluorodeoxyglucose positron emission tomography (PET) scan typically carries a poor prognosis. In this prospective multi-center phase II study, we sought to establish whether treatment intensification with R-ICE (rituximab, ifosfamide, carboplatin, and etoposide) chemotherapy followed by 90Y-ibritumomab tiuxetan-BEAM (BCNU, etoposide, cytarabine, and melphalan) for high-risk diffuse large B-cell lymphoma patients who are positive on interim PET scan after 4 cycles of R-CHOP-14 (rituximab, cyclophosphamide, doxorubicin, and prednisone) can improve 2-year progression-free survival from a historically unfavorable rate of 40% to a rate of 65%...
February 2017: Haematologica
https://www.readbyqxmd.com/read/28143565/disulfiram-overcomes-bortezomib-and-cytarabine-resistance-in-down-syndrome-associated-acute-myeloid-leukemia-cells
#14
Ranjan Bista, David W Lee, Oliver B Pepper, David O Azorsa, Robert J Arceci, Eiman Aleem
BACKGROUND: Children with Down syndrome (DS) have increased risk for developing AML (DS-AMKL), and they usually experience severe therapy-related toxicities compared to non DS-AMKL. Refractory/relapsed disease has very poor outcome, and patients would benefit from novel, less toxic, therapeutic strategies that overcome resistance. Relapse/resistance are linked to cancer stem cells with high aldehyde dehydrogenase (ALDH) activity. The purpose of the present work was to study less toxic alternative therapeutic agents for relapsed/refractory DS-AMKL...
February 1, 2017: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/28138160/impact-of-salvage-regimens-on-response-and-overall-survival-in-acute-myeloid-leukemia-with-induction-failure
#15
M Wattad, D Weber, K Döhner, J Krauter, V I Gaidzik, P Paschka, M Heuser, F Thol, T Kindler, M Lübbert, H R Salih, A Kündgen, H-A Horst, P Brossart, K Götze, D Nachbaur, C-H Köhne, M Ringhoffer, G Wulf, G Held, H Salwender, A Benner, A Ganser, H Döhner, R F Schlenk
We evaluated the impact of salvage regimens and allogeneic hematopoietic cell transplantation (allo-HCT) in acute myeloid leukemia (AML) with induction failure. Between 1993 and 2009, 3324 patients with newly diagnosed AML were enrolled in 5 prospective treatment trials of the German-Austrian AML Study Group. After first induction therapy with idarubicin, cytarabine and etoposide (ICE), 845 patients had refractory disease. In addition, 180 patients, although responding to first induction, relapsed after second induction therapy...
February 10, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28137265/targeting-acute-myeloid-leukemia-stem-cell-signaling-by-natural-products
#16
REVIEW
Kodappully Sivaraman Siveen, Shahab Uddin, Ramzi M Mohammad
Acute myeloid leukemia (AML) is the most commonly diagnosed leukemia in adults (25%) and comprises 15-20% in children. It is a genetically heterogeneous aggressive disease characterized by the accumulation of somatically acquired genetic changes, altering self-renewal, proliferation, and differentiation of hematopoietic progenitor cells, resulting in uncontrolled clonal proliferation of malignant progenitor myeloid cells in the bone marrow, peripheral blood, and occasionally in other body tissues. Treatment with modern chemotherapy regimen (cytarabine and daunorubicin) usually achieves high remission rates, still majority of patients are found to relapse, resulting in only 40-45% overall 5 year survival in young patients and less than 10% in the elderly AML patients...
January 30, 2017: Molecular Cancer
https://www.readbyqxmd.com/read/28129526/addition-of-androgens-improves-survival-in-elderly-patients-with-acute-myeloid-leukemia-a-goelams-study
#17
Arnaud Pigneux, Marie C Béné, Philippe Guardiola, Christian Recher, Jean-Francois Hamel, Mathieu Sauvezie, Jean-Luc Harousseau, Olivier Tournilhac, Francis Witz, Christian Berthou, Martine Escoffre-Barbe, Denis Guyotat, Nathalie Fegueux, Chantal Himberlin, Mathilde Hunault, Martine Delain, Bruno Lioure, Eric Jourdan, Frederic Bauduer, Francois Dreyfus, Jean-Yves Cahn, Jean-Jacques Sotto, Norbert Ifrah
Purpose Elderly patients with acute myeloid leukemia (AML) have a poor prognosis, and innovative maintenance therapy could improve their outcomes. Androgens, used in the treatment of aplastic anemia, have been reported to block proliferation of and initiate differentiation in AML cells. We report the results of a multicenter, phase III, randomized open-label trial exploring the benefit of adding androgens to maintenance therapy in patients 60 years of age or older. Patients and Methods A total of 330 patients with AML de novo or secondary to chemotherapy or radiotherapy were enrolled in the study...
February 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28125133/acute-wt1-positive-promyelocytic-leukemia-with-hypogranular-variant-morphology-bcr-3-isoform-of-pml-rar%C3%AE-and-flt3-itd-mutation-a-rare-case-report
#18
Xi Zhang, Cheng Yang, Xiangui Peng, Xinghua Chen, Yimei Feng
CONTEXT: Acute promyelocytic leukemia (APL) accounts for 8% to 10% of cases of acute myeloid leukemia (AML). Remission in cases of high-risk APL is still difficult to achieve, and relapses occur readily. CASE REPORT: Here, we describe a case of APL with high white blood cell counts in blood tests and hypogranular variant morphology in bone marrow, together with fms-like tyrosine kinase-3 with internal tandem duplication mutations (FLT3-ITD), and bcr-3 isoform of PML-RARα...
January 23, 2017: São Paulo Medical Journal, Revista Paulista de Medicina
https://www.readbyqxmd.com/read/28123146/intesive-fludarabine-high-dose-cytarabine-idarubicin-combination-as-induction-therapy-with-risk-adapted-consolidation-may-improve-treatment-efficacy-in-younger-acute-myeloid-leukemia-aml-patients-rationales-evidences-and-future-perspectives
#19
Fabio Guolo, Paola Minetto, Marino Clavio, Maurizio Miglino, Roberto Massimo Lemoli, Marco Gobbi
Acute Myeloid Leukemia (AML) is the commonest form of leukemia in the adults, with an incidence of 3-4 cases per 100,000 people/year. After the first description of the effective cytarabine + antracycline (3+7) induction regimen, in the last 3 decades, no effective targeted drug has been included in the standard treatment of AML. Many efforts of modifying 3+7 adding a third drug or increasing the dose of anthracycline, cytarabine or both did not lead to substantial improvements, mainly due to increased toxicity...
January 24, 2017: Bioscience Trends
https://www.readbyqxmd.com/read/28122150/impact-of-body-surface-area-on-patients-outcome-in-younger-adults-with-acute-myeloid-leukemia
#20
X Cahu, M Carré, C Recher, A Pigneux, M Hunault-Berger, N Vey, P Chevallier, J Delaunay, E Gyan, B Lioure, C Bonmati, C Himberlin, Y Hichri, G Guillerm, D Bouscary, F Larosa, M Ojeda-Uribe, M Bernard, M C Béné, N Ifrah, J Y Cahn
OBJECTIVES: anthracyclins and cytarabine are cornerstones for intensive chemotherapy in acute myeloid leukemia (AML). The goals of this study were to comprehensively assess deviations from theoretical doses and the impact of body surface area (BSA) on patients' characteristics, physicians' strategy, dose adjustment and clinical outcome. METHODS: The GOELAMS 2001 phase III trial included 823 AML patients below 60 years of age. In the course of treatment, anthropomorphic parameters and chemotherapy doses were prospectively registered...
January 25, 2017: European Journal of Haematology
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