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Jing Liu, Dujuan Zhao, Wenxiu He, Huiyuan Zhang, Zhonghao Li, Yuxia Luan
The anti-leukemia effect of cytarabine (Ara-C) is severely restricted by its high hydrophilic properties and rapid plasma degradation. Herein, a novel amphiphilic small molecular prodrug of Ara-C was developed by coupling a short aliphatic chain, hexanoic acid (HA) to 4-NH2 of the parent drug. Based on the amphiphilic nature, the resulting bioconjugate (HA-Ara) could spontaneously self-assemble into stable spherical nanoassemblies (NAs) with an extremely high drug loading (∼71wt%). Moreover, folate receptor (FR)-targeting NAs with high grafting efficient folic acid - bovine serum albumin (FA-BSA) conjugate immobilized on the surface (NAs/FA-BSA) was prepared...
October 19, 2016: Journal of Colloid and Interface Science
R Pola, O Janoušková, T Etrych
Cytarabine is one of the most efficient drugs in the treatment of hematological malignancies. In this work, we describe the synthesis and characterization of two different polymer conjugates of cytarabine that were designed for the controlled release of cytarabine within the leukemia cells. Reactive copolymers of N-(2-hydroxypropyl)methacrylamide (HPMA) and 3-(3-methacrylamidopropa-noyl)thiazolidine-2-thione) or 3-(Nmethacryloylglycyl-phenylalanylleucylglycyl)thiazolidine-2-thione were used in the study as reactive polymer precursors for reaction with cytarabine...
October 20, 2016: Physiological Research
Nahid Shahabadi, Monireh Falsafi, Maryam Maghsudi
The interaction of anticancer drug cytarabine with calf thymus DNA (CT-DNA) was investigated in vitro under simulated physiological conditions by multispectroscopic techniques and molecular modeling study. The fluorescence spectroscopy and UV absorption spectroscopy indicated drug interacted with CT-DNA in a groove-binding mode, while the binding constant of UV-vis and the number of binding sites were 4.0 ± 0.2 × 10(4) L mol(-1) and 1.39, respectively. The fluorimetric studies showed that the reaction between the drugs with CT-DNA is exothermic...
October 19, 2016: Nucleosides, Nucleotides & Nucleic Acids
M Wu, M Hamaker, L Li, D Small, A S Duffield
The FMS-like tyrosine kinase-3 (FLT3) gene is the most commonly mutated gene in acute myeloid leukemia (AML), and patients carrying internal tandem duplication (ITD) mutations have a poor prognosis. Long-term inhibition of FLT3 activity in these patients has been elusive. To provide a more complete understanding of FLT3 biology, a mass spectroscopy-based screen was performed to search for FLT3-interacting proteins. The screen identified dedicator of cytokinesis 2 (DOCK2), which is a guanine nucleotide exchange factor for Rho GTPases, and its expression is limited to hematolymphoid cells...
October 17, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
Nikolai A Podoltsev, Maximilian Stahl, Amer M Zeidan, Steven D Gore
More than half of the patients with acute myeloid leukaemia (AML) are older than 60years. The treatment outcomes in this group remain poor with a median overall survival of <1year. Selecting initial treatment for these patients involves an assessment of 'fitness' for induction chemotherapy. This is done based on patient and disease-related characteristics which help to estimate treatment-related mortality and chance of complete remission with induction chemotherapy. If the risk of treatment-related mortality is high and/or the likelihood of a patient achieving a complete remission is low, lower-intensity treatment (low-dose cytarabine, decitabine and azacitidine) should be discussed...
October 8, 2016: Blood Reviews
Elias Jabbour, Stefan Faderl, Koji Sasaki, Tapan Kadia, Naval Daver, Naveen Pemmaraju, Keyur Patel, Joseph D Khoury, Carlos Bueso-Ramos, Zachary Bohannan, Farhad Ravandi, Gautam Borthakur, Srdan Verstovsek, Darla Miller, Rita Maduike, Chitra Hosing, Hagop M Kantarjian, Guillermo Garcia-Manero
BACKGROUND: The outcome of patients with higher risk myelodysplastic syndromes (MDS) after hypomethylating agent (HMA) failure is poor. This study evaluated the safety and activity of a combination of low-dose clofarabine and cytarabine for these patients. METHODS: Seventy patients with higher risk MDS who had no response, progressed, or relapsed after at least 4 cycles of HMA therapy were treated. RESULTS: The median age was 72 years. Thirty-nine percent of the patients had high-risk disease according to the International Prognostic Scoring System, and 50% of the patients had poor-risk cytogenetics...
October 14, 2016: Cancer
Savitha Varatharajan, John C Panetta, Ajay Abraham, Sreeja Karathedath, Ezhilpavai Mohanan, Kavitha M Lakshmi, Nancy Arthur, Vivi M Srivastava, Sandeep Nemani, Biju George, Alok Srivastava, Vikram Mathews, Poonkuzhali Balasubramanian
PURPOSE: Chemotherapy drug resistance and relapse of the disease have been the major factors limiting the success of acute myeloid leukemia (AML) therapy. Several factors, including the pharmacokinetics (PK) of Cytarabine (Ara-C) and Daunorubicin (Dnr), could contribute to difference in treatment outcome in AML. METHODS: In the present study, we evaluated the plasma PK of Dnr, the influence of genetic polymorphisms of genes involved in transport and metabolism of Dnr on the PK, and also the influence of these factors on clinical outcome...
October 13, 2016: Cancer Chemotherapy and Pharmacology
Honglei Tu, Bo Lei, Shan Meng, Hailing Liu, Yongchang Wei, Aili He, Wanggang Zhang, Fuling Zhou
We assessed the clinical effectiveness and safety of CKI (compound Kushen injection) plus standard induction chemotherapy for treating adult acute leukemia (AL). We randomly assigned 332 patients with newly diagnosed AL to control (n = 165, receiving DA (daunorubicin and cytarabine) or hyper-CVAD (fractionated cyclophosphamide, doxorubicin, vincristine, and dexamethasone)) or treatment (n = 167, receiving CKI and DA or hyper-CVAD) groups. Posttreatment, treatment group CD3+, CD4+, CD4+/CD8+, natural killer (NK) cell, and immunoglobulin (IgG, IgA, and IgM) levels were significantly higher than those of the control group (p < 0...
2016: Evidence-based Complementary and Alternative Medicine: ECAM
Chantal Fridle, Michael Medinger, Matthias C Wilk, Katja Seipel, Jakob Passweg, Markus G Manz, Thomas Pabst
BACKGROUND: The prognosis for relapsing AML patients is disappointing and the preferred salvage chemotherapy is unclear. Among other regimens, cladribine, cytarabine, and idarubicin (CLA-Ida) is used. METHODS: We analyzed relapsing AML patients receiving CLA-Ida chemotherapy between July 2012 and April 2015 at three academic centers in Switzerland. RESULTS: Thirty-four patients underwent at least one cycle of CLA-Ida chemotherapy, with 6 patients having two cycles...
October 13, 2016: Leukemia & Lymphoma
Ayumi Tsukamoto, Shunji Ishiwata, Asami Kajimoto, Ryusuke Murata, Rika Kitano, Tomomi Inoue, Takeshi Kotake
BACKGROUND: Exposure to anticancer drugs is hazardous and may lead to chromosomal abnormalities and spontaneous abortion in healthcare workers. Guidelines recommend surface decontamination and cleaning in order to minimize the occupational exposure to anticancer drugs, although no single process has been found to deactivate all currently available hazardous drugs. Ozone gas is oxidative and a decontaminant for bacteria; its characteristic as a gas has advantages in that it does not need to be wiped off or neutralized after use...
2016: Journal of Pharmaceutical Health Care and Sciences
Hui Liu, Rong Fu, Lijuan Li, Guojin Wang, Jia Song, Erbao Ruan, Huaquan Wang, Yuhong Wu, Xiaoming Wang, Kai Ding, Zonghong Shao
BACKGROUND AND OBJECTIVES: The therapy in elderly patients with acute myeloid leukemia (AML) is a big challenge because of poor risk factors and inferior tolerance to intensive chemotherapy. This study aims to compare the efficacy between reduced-intensity idarubicin plus cytarabine and daunorubicin plus cytarabine (IA regimen and DA regimen, respectively) in elderly patients with newly diagnosed AML. METHODS: We retrospectively investigated 74 patients with newly diagnosed non-M3 AML aged >60 years, where 33 patients received IA regimen, 30 patients received DA regimen, while 11 patients received supportive treatment...
October 8, 2016: Clinical Drug Investigation
Christoph Schliemann, Joachim Gerss, Stefanie Wiebe, Jan-Henrik Mikesch, Nicola Knoblauch, Tim Sauer, Linus Angenendt, Tobias Kewitz, Marc Urban, Trude Butterfass-Bahloul, Sabine Edemir, Kerstin Vehring, Carsten Müller-Tidow, Wolfgang E Berdel, Utz Krug
: Nintedanib (BIBF 1120), a potent multikinase inhibitor of VEGFR-1/-2/-3, FGFR-1/-2/-3 and PDGFR-α/-β, exerts growth inhibitory and pro-apoptotic effects in myeloid leukemic cells, especially when used in combination with cytarabine. This phase I study evaluated nintedanib in combination with low-dose cytarabine (LDAC) in elderly patients with untreated or relapsed/refractory acute myeloid leukemia (AML) ineligible for intensive chemotherapy in a 3+3 design. Nintedanib (dose levels 100, 150, and 200 mg orally twice daily) and LDAC (20 mg subcutaneous injection twice daily for 10 days) were administered in 28-day cycles...
2016: PloS One
Jiang Cao, Hao Feng, Ning-Ning Ding, Qing-Yun Wu, Chong Chen, Ming-Shan Niu, Wei Chen, Ting-Ting Qiu, Hong-Hu Zhu, Kai-Lin Xu
Homoharringtonine combined with aclarubicin and cytarabine (HAA) is a highly effective treatment for acute myeloid leukemia (AML), especially for t(8;21) AML. However, the underlying mechanisms by which HAA kills t(8;21) AML cells remain unclear. In this study, SKNO-1 and Kasumi-1 cells with t(8;21) were used. Compared with individual or pairwise administration of homoharringtonine, aclarubicin, or cytarabine, HAA showed the strongest inhibition of growth and induction of apoptosis in SKNO-1 and Kasumi-1 cells...
October 5, 2016: Cancer Medicine
Zhi Guo, Hong-Yan Gao, Tian-Yan Zhang, Xiao-Dong Liu, Kai Yang, Jing-Xing Lou, Xue-Peng He, Yuan Zhang, Peng Chen, Hui-Ren Chen
The study was aimed to explore the efficacy and safety of allo-HSCT with high-dose cyclophosphamide-induced immune tolerance for SAA. In the present study, 20 cases (12 male, 8 female; average age = 17.8 years) received reduced-intensity conditioning allo-HSCT from August 2012 to August 2014 in the Beijing Military Region General Hospital. All were HLA mismatched and received CSA; 11 received ATG-intensive immune therapy. Donors underwent mobilization with cell colony-stimulating factor. The modified preconditioning regimen included reduced-strength fludarabine combined with Busulfex and cytarabine, cyclophosphamide...
October 5, 2016: International Journal of Hematology
Mixue Xie, Qi Jiang, Li Li, Jingjing Zhu, Lixia Zhu, De Zhou, Yanlong Zheng, Xiudi Yang, Mingyu Zhu, Jianai Sun, Wanzhuo Xie, Xiujin Ye
BACKGROUND: In China, the combination of homoharringtonine, cytarabine, and G-CSF (HAG) has been extensively applied for treatment of acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). METHODS: We performed a meta-analysis of 2,314 patients (AML, n = 1754; MDS, n = 560) to determine the overall safety and efficacy of this regimen. RESULTS: The complete response (CR) rate of AML patients (53%) was significantly higher than that of MDS/transformed-AML patients (45%; P = 0...
2016: PloS One
Richard F Schlenk, Michael Lübbert, Axel Benner, Alexander Lamparter, Jürgen Krauter, Wolfgang Herr, Hans Martin, Helmut R Salih, Andrea Kündgen, Heinz-A Horst, Peter Brossart, Katharina Götze, David Nachbaur, Mohammed Wattad, Claus-Henning Köhne, Walter Fiedler, Martin Bentz, Gerald Wulf, Gerhard Held, Bernd Hertenstein, Hans Salwender, Verena I Gaidzik, Brigitte Schlegelberger, Daniela Weber, Konstanze Döhner, Arnold Ganser, Hartmut Döhner
The aim of this clinical trial was to evaluate the impact of all-trans retinoic acid (ATRA) in combination with chemotherapy and to assess the NPM1 status as biomarker for ATRA therapy in younger adult patients (18-60 years) with acute myeloid leukemia (AML). Patients were randomized for intensive chemotherapy with or without open-label ATRA (45 mg/m(2), days 6-8; 15 mg/m(2), days 9-21). Two cycles of induction therapy were followed by risk-adapted consolidation with high-dose cytarabine or allogeneic hematopoietic cell transplantation...
October 3, 2016: Annals of Hematology
Chen Tian, Yizhuo Zhang
INTRODUCTION: Most primary stomach lymphomas are now recognized to originate from B-cell. Primary gastric anaplastic lymphoma kinase (ALK)-negative anaplastic large-cell lymphoma (ALCL) as shown in this case is very rare. CASE REPORT: A 59-year-old man presented with a 1-month history of epigastric pain. Computed tomography showed a tumor in the stomach with perigastric lymphadenopathy. Biopsy of the tumor with gastroendoscopy showed ALCL. Bone marrow aspiration and trephine biopsy showed no infiltration...
2016: OncoTargets and Therapy
O Nibourel, S Guihard, C Roumier, N Pottier, C Terre, A Paquet, P Peyrouze, S Geffroy, S Quentin, A Alberdi, R B Abdelali, A Renneville, C Demay, K Celli-Lebras, P Barbry, B Quesnel, S Castaigne, H Dombret, J Soulier, C Preudhomme, M H Cheok
Recent advances in genomic technologies have revolutionized acute myeloid leukemia (AML) understanding by identifying potential novel actionable genomic alterations. Consequently, current risk stratification at diagnosis not only relies on cytogenetics but also on the inclusion of several of these abnormalities. Despite this progress, AML remains a heterogeneous and complex malignancy with variable response to current therapy. Although copy number alterations (CNA) are accepted prognostic markers in cancers, large-scale genomic studies aiming at identifying specific prognostic CNA-based markers in AML are still lacking...
September 30, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
Ruiqi Li, Xiaoxia Hu, Libing Wang, Hui Cheng, Shuqing Lv, Weiping Zhang, Jianmin Wang, Jianmin Yang, Xianmin Song
Acute myeloid leukemia (AML) patients with t(8;21) aberration often have favorable outcomes, however, relapse still occurs in 30-40% patients, with only 50-60% of patients with t(8;21) AML cured with regimens containing high-dose cytarabine (HD-Ara-C). To evaluate the effects of fludarabine and cytarabine (FA) consolidation therapy for t(8;21) AML patients, a prospective randomized study was performed. A total of 45 patients with t(8;21) AML after achieving complete remission (CR) were randomly assigned to receive four course consolidation with FA (n = 23) or HD-Ara-C (n = 22)...
September 27, 2016: American Journal of Hematology
Aleksandra Szulc, Lukasz Pulaski, Dietmar Appelhans, Brigitte Voit, Barbara Klajnert-Maculewicz
Maltose-modified poly(propylene imine) glycodendrimers (PPI-m OS) of the 4th generation provide a promising strategy for leukemia treatment. Anticancer therapy with nucleoside analog drugs such as cytarabine (Ara-C) frequently has limited efficacy due to drug resistance, inefficient uptake and accumulation of the drug inside cancer cells where it has to be transformed into the active triphosphate congener. The cationic nature of PPI dendrimers makes it possible to form complexes with nucleotide Ara-C triphosphate forms (Ara-CTP)...
September 22, 2016: International Journal of Pharmaceutics
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