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https://www.readbyqxmd.com/read/28644630/expanding-the-therapeutic-potential-of-the-iron-chelator-deferasirox-in-the-development-of-aqueous-stable-ti-iv-anticancer-complexes
#1
Sergio A Loza-Rosas, Alexandra M Vázquez-Salgado, Kennett I Rivero, Lenny J Negrón, Yamixa Delgado, Josué A Benjamín-Rivera, Angel L Vázquez-Maldonado, Timothy B Parks, Charlene Munet-Colón, Arthur D Tinoco
The recent X-ray structure of titanium(IV)-bound human serum transferrin (STf) exhibiting citrate as a synergistic anion reveals a difference in Ti(IV) coordination versus iron(III), the metal endogenously delivered by the protein to cells. This finding enriches our bioinspired drug design strategy for Ti(IV)-based anticancer therapeutics, which applies a family of Fe(III) chelators termed chemical transferrin mimetic (cTfm) ligands to inhibit Fe bioavailability in cancer cells. Deferasirox, a drug used for iron overload disease, is a cTfm ligand that models STf coordination to Fe(III), favoring Fe(III) binding versus Ti(IV)...
June 23, 2017: Inorganic Chemistry
https://www.readbyqxmd.com/read/28621205/neurocognitive-dysfunction-in-children-with-%C3%AE-thalassemia-major-psychometric-neurophysiologic-and-radiologic-evaluation
#2
M S Elalfy, R H Aly, H Azzam, K Aboelftouh, R H Shatla, M Tarif, M Abdatty, R M Elsayed
OBJECTIVE: To evaluate the impact of iron chelating drugs and serum ferritin on the neurocognitive functions of patients with β thalassemia major (β-TM), using psychometric, neurophysiologic and radiologic tests. METHODS: Eighty children with β-TM were enrolled into the study and were compared to 40 healthy controls. All participants were evaluated by measuring serum ferritin, neurocognitive assessment by Benton Visual Retention Test, Wechsler Intelligence Scale for Children, Wisconsin Card Sort Test, P300 and magnetic resonance spectroscopy (MRS)...
June 16, 2017: Hematology (Amsterdam, Netherlands)
https://www.readbyqxmd.com/read/28556939/a-case-of-fanconi-syndrome-due-to-a-deferasirox-overdose-and-a-trial-of-plasmapheresis
#3
L Shah, J L Powell, J J Zaritsky
WHAT IS KNOWN AND OBJECTIVE: Deferasirox has nephrotoxic effects in the context of chronic therapy. This case report illustrates proximal tubular dysfunction (Fanconi syndrome) due to an acute deferasirox overdose. CASE DESCRIPTION: In response, we trialled plasmapheresis to eliminate the drug. Deferasirox levels were obtained in the context of three rounds of plasmapheresis. Given the half-life model of decay, we concluded that plasmapheresis may not have been successful...
May 29, 2017: Journal of Clinical Pharmacy and Therapeutics
https://www.readbyqxmd.com/read/28421266/reactive-oxygen-species-mediated-t-lymphocyte-abnormalities-in-an-iron-overloaded-mouse-model-and-iron-overloaded-patients-with-myelodysplastic-syndromes
#4
Jie Chen, Wen-Yi Lu, Ming-Feng Zhao, Xiao-Li Cao, Yan-Yu Jiang, Xin Jin, Ping Xu, Ting-Ting Yuan, Yu-Chen Zhang, Xiao Chai, Juan-Xia Meng, Qing Li, Xia Xiao, Juan Mu, De-Guan Li, Ai-Ping Qi
The adverse effects of iron overload have raised more concerns as a growing number of studies reported its association with immune disorders. This study aimed to investigate alterations in the immune system by iron overload in patients with myelodysplastic syndrome (MDS) and an iron-overloaded mouse model. The peripheral blood from patients was harvested to test the effect of iron overload on the subsets of T lymphocytes, and the level of reactive oxygen species (ROS) was also evaluated. The data showed that iron-overloaded patients had a lower percentage of CD3(+) T cells and disrupted T cell subsets, concomitant with higher ROS level in lymphocytes...
July 2017: Annals of Hematology
https://www.readbyqxmd.com/read/28419408/iron-chelating-therapy-with-deferasirox-in-transfusion-dependent-higher-risk-myelodysplastic-syndromes-a-retrospective-multicentre-study
#5
Pellegrino Musto, Luca Maurillo, Vittorio Simeon, Antonella Poloni, Carlo Finelli, Enrico Balleari, Alessandra Ricco, Flavia Rivellini, Agostino Cortelezzi, Giuseppe Tarantini, Oreste Villani, Giovanna Mansueto, Maria R Milella, Daniele Scapicchio, Gioacchino Marziano, Massimo Breccia, Pasquale Niscola, Alessandro Sanna, Cristina Clissa, Maria T Voso, Susanna Fenu, Adriano Venditti, Valeria Santini, Emanuele Angelucci, Alessandro Levis
Iron chelation is controversial in higher risk myelodysplastic syndromes (HR-MDS), outside the allogeneic transplant setting. We conducted a retrospective, multicentre study in 51 patients with transfusion-dependent, intermediate-to-very high risk MDS, according to the revised international prognostic scoring system, treated with the oral iron chelating agent deferasirox (DFX). Thirty-six patients (71%) received azacitidine concomitantly. DFX was given at a median dose of 1000 mg/day (range 375-2500 mg) for a median of 11 months (range 0·4-75)...
June 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28404539/a-national-registry-of-thalassemia-in-turkey-demographic-and-disease-characteristics-of-patients-achievements-and-challenges-in-prevention
#6
Yeşim Aydınok, Yeşim Oymak, Berna Atabay, Gönül Aydoğan, Akif Yeşilipek, Selma Ünal, Yurdanur Kılınç, Banu Oflaz, Mehmet Akın, Canan Vergin, Melike Sezgin Evim, Ümran Çalışkan, Şule Ünal, Ali Bay, Elif Kazancı, Dilber Talia İleri, Didem Atay, Türkan Patıroğlu, Selda Kahraman, Murat Söker, Mediha Akcan, Aydan Akdeniz, Mustafa Büyükavcı, Güçhan Alanoğlu, Özcan Bör, Nur Soyer, Nihal Özdemir Karadaş, Ezgi Uysalol, Meral Türker, Arzu Akçay, Süheyla Ocak, Adalet Meral Güneş, Hüseyin Tokgöz, Zümrüt Uysal, Naci Tiftik, Zeynep Karakaş
Turkish Society of Pediatric Hematology set up a National Hemoglobinopathy Registry to demonstrate demographic and disease characteristics of patients, and assessed the efficacy of hemoglobinopathy control program (HCP) over 10 years in Turkey. A total of 2046 patients from 27 Thalassemia Centers were registered in which 1988 were eligible for analysis. This cohort mainly comprised patients with β-thalassemia major (n=1658, 83.4%) and intermedia (n=215, 10.8%). The majority of patients were accumulated into the costal areas of Turkey...
April 13, 2017: Turkish Journal of Haematology: Official Journal of Turkish Society of Haematology
https://www.readbyqxmd.com/read/28388554/synergistic-inhibitory-effects-of-deferasirox-in-combination-with-decitabine-on-leukemia-cell-lines-skm-1-thp-1-and-k-562
#7
Nianyi Li, Qinfen Chen, Jingwen Gu, Shuang Li, Guangjie Zhao, Wei Wang, Zhicheng Wang, Xiaoqin Wang
A multi-center study from the French Myelodysplastic Syndrome (MDS) Group confirmed that iron chelation therapy is an independent prognostic factor that can increase the survival rate of patients who are suffering from transfusion-dependent low-risk MDS. In this study, we aimed to explore this clinical phenomena in vitro, by exploring the synergistic effect of the iron chelator Deferasirox (DFX) and the DNA methyl transferase inhibitor Decitabine (DAC) in the leukemia cell lines SKM-1, THP-1, and K-562. Treatment with both DFX or DAC promoted apoptosis, induced cell cycle arrest, and inhibited proliferation in all three of these cell lines...
May 30, 2017: Oncotarget
https://www.readbyqxmd.com/read/28384880/efficacy-of-deferasirox-as-an-oral-iron-chelator-in-paediatric-thalassaemia-patients
#8
Shikha Jaiswal, Rajesh Hishikar, Onkar Khandwal, Manju Agarwal, Usha Joshi, Ajay Halwai, Basant Maheshwari, Raka Sheohare
INTRODUCTION: Thalassaemia Major patients require frequent blood transfusion leading to iron overload. Excessive iron gets deposited in vital organs and leads to dysfunction of the heart, liver, anterior pituitary, pancreas, and joints. Our body has limited mechanism to excrete iron, so patients with iron overload and its complications need safe and effective iron chelation therapy. AIM: To assess the efficacy of Deferasirox (DFX) as an iron chelator, with specific reference to reduction in serum ferritin level...
February 2017: Journal of Clinical and Diagnostic Research: JCDR
https://www.readbyqxmd.com/read/28361176/electrophysiological-assessment-for-early-detection-of-retinal-dysfunction-in-%C3%AE-thalassemia-major-patients
#9
Maria Dettoraki, Antonis Kattamis, Ioannis Ladas, Konstantinos Maragkos, Chryssanthi Koutsandrea, Klio Chatzistefanou, Konstantinos Laios, Dimitrios Brouzas, Marilita M Moschos
PURPOSE: The purpose of this study was to assess the role of various diagnostic tests in early detection of retinal changes in β-thalassemia major patients. METHODS: Thirty-eight visually asymptomatic β-thalassemia major patients receiving regular blood transfusions and iron-chelation therapy with deferoxamine (group A, n = 13), deferasirox (group B, n = 11) or deferoxamine with deferiprone (group C, n = 14) and fourteen age- and sex- matched healthy individuals were included in the study...
July 2017: Graefe's Archive for Clinical and Experimental Ophthalmology
https://www.readbyqxmd.com/read/28346059/deferasirox-pharmacogenetic-influence-on-pharmacokinetic-efficacy-and-toxicity-in-a-cohort-of-pediatric-patients
#10
Sarah Allegra, Silvia De Francia, Jessica Cusato, Arianna Arduino, Davide Massano, Filomena Longo, Antonio Piga, Antonio D'Avolio
AIM: We aimed to evaluate the influence of genetic polymorphisms involved in deferasirox metabolism and transport on its pharmacokinetics and treatment toxicity, in a cohort of β-thalassaemic children. PATIENTS & METHODS: Drug plasma concentrations were measured by a HPLC-UV method. Allelic discrimination for UGT1A1, UGT1A3, CYP1A1, CYP1A2, CYP2D6, MRP2 and BCRP1 polymorphisms was performed by real-time PCR. RESULTS: CYP1A1 rs2606345AA influenced Ctrough (p = 0...
March 27, 2017: Pharmacogenomics
https://www.readbyqxmd.com/read/28332891/the-positive-effect-of-deferasirox-on-erythropoiesis-in-a-patient-with-a-dual-diagnosis-of-myelofibrosis-and-diffuse-large-b-cell-lymphoma
#11
Louise Kostos, Khai Li Chai, Constantine S Tam, Ali Bazargan
No abstract text is available yet for this article.
March 23, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28316434/comparison-of-deferasirox-and-deferoxamine-effects-on-iron-overload-and-immunological-changes-in-patients-with-blood-transfusion-dependent-%C3%AE-thalassemia
#12
Hayder M Al-Kuraishy, Ali I Al-Gareeb
INTRODUCTION: Beta-thalassemias are a cluster of inherited (autosomal recessive) hematological disorders prevalent in the Mediterranean area due to defects in synthesis of β chains of hemoglobin. The aim of present study was to compare the effects of deferasirox and deferoxamine on iron overload and immunological changes in patients with blood transfusion-dependent β-thalassemia major and intermedia. PATIENTS AND METHODS: This study involved 64 patients with known cases of β-thalassemia major or intermedia that has been treated with blood transfusion and iron chelators...
January 2017: Asian Journal of Transfusion Science
https://www.readbyqxmd.com/read/28296163/long-term-safety-and-efficacy-of-deferasirox-in-young-pediatric-patients-with-transfusional-hemosiderosis-results-from-a-5-year-observational-study-entrust
#13
Elliott Vichinsky, Amal El-Beshlawy, Azzam Al Zoebie, Annie Kamdem, Suzanne Koussa, Thirachit Chotsampancharoen, Andreas Bruederle, Geralyn Gilotti, Jackie Han, Mohsen Elalfy
BACKGROUND: Children with red blood cell disorders may receive regular transfusions from an early age and consequently accumulate iron. Adequate iron chelation therapy can prevent organ damage and delayed growth/development. Deferasirox is indicated for treatment of pediatric patients with chronic iron overload due to transfusional hemosiderosis; however, fewer than 10% of patients in the registration studies were aged 2 to less than 6 years. PROCEDURE: Deferasirox, a once-daily oral iron chelator, was evaluated in young pediatric patients with transfusional hemosiderosis during the observational 5-year ENTRUST study...
March 10, 2017: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/28287621/restoring-the-impaired-cardiac-calcium-homeostasis-and-cardiac-function-in-iron-overload-rats-by-the-combined-deferiprone-and-n-acetyl-cysteine
#14
Suwakon Wongjaikam, Sirinart Kumfu, Juthamas Khamseekaew, Siriporn C Chattipakorn, Nipon Chattipakorn
Intracellular calcium [Ca(2+)]i dysregulation plays an important role in the pathophysiology of iron overload cardiomyopathy. Although either iron chelators or antioxidants provide cardioprotection, a comparison of the efficacy of deferoxamine (DFO), deferiprone (DFP), deferasirox (DFX), N-acetyl cysteine (NAC) or a combination of DFP plus NAC on cardiac [Ca(2+)]i homeostasis in chronic iron overload has never been investigated. Male Wistar rats were fed with either a normal diet or a high iron (HFe) diet for 4 months...
March 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28248443/iron-overload-induces-apoptosis-of-murine-preosteoblast-cells-via-ros-and-inhibition-of-akt-pathway
#15
J-Y Ke, W-J Cen, X-Z Zhou, Y-R Li, W-D Kong, J-W Jiang
OBJECTIVE: This study investigates the inhibitory effect of iron overload on MC3T3-E1 cells and its molecular mechanism. METHODS: MC3T3-E1 cells were grown under different concentrations of FAC (ferric ammonium citrate), and the WST-8 assay was used to investigate the proliferation of cells following FAC with or without deferasirox. DCFH-DA fluorescence probe was applied to detect the cellular reactive oxygen species (ROS) level. The apoptotic cells were analyzed with Annexin V-FITC/PI and the Hoechst 33258 nuclear staining assay...
March 1, 2017: Oral Diseases
https://www.readbyqxmd.com/read/28243431/combination-iron-chelation-therapy-with-deferiprone-and-deferasirox-in-iron-overloaded-patients-with-transfusion-dependent-%C3%AE-thalassemia-major
#16
Hossein Karami, Mehrnoush Kosaryan, Arash Hadian Amree, Hadi Darvishi-Khezri, Masoomeh Mousavi
There are few papers on the combination therapy of deferiprone (DFP) and deferasirox (DFX) in iron-overloaded patients with transfusion-dependent β-thalassemia major (β-TM). A total of 6 patients with β-TM (5 males and 1 female) with a mean age of 23.8±5.8 years (ranging from 17 to 31) used this treatment regimen. The mean doses of DFP and DFX were 53.9±22.2 and 29.3±6.8 mg/kg/day, respectively. The duration of treatment was 11.5±4.6 months. Their serum ferritin levels were measured to be 2800±1900 and 3400±1600 ng/mL before and after treatment, respectively (p<0...
January 11, 2017: Clinics and Practice
https://www.readbyqxmd.com/read/28221265/acute-liver-failure-during-deferasirox-chelation-a-toxicity-worth-considering
#17
Nathan Menaker, Katharine Halligan, Natasha Shur, John Paige, Matthew Hickling, Anne Nepo, Lauren Weintraub
This case report details a unique case of acute, reversible liver failure in a 12-year-old male with sickle cell anemia on chronic transfusion protocol and deferasirox chelation. There is substantial literature documenting deferasirox-induced renal injury, including Fanconi syndrome, but less documentation of hepatic toxicity and few reports of hepatic failure. The case highlights the importance of close monitoring of ferritin, bilirubin, and transaminases for patients on deferasirox.
April 2017: Journal of Pediatric Hematology/oncology
https://www.readbyqxmd.com/read/28221264/efficacy-and-safety-of-combined-oral-chelation-with-deferiprone-and-deferasirox-in-children-with-%C3%AE-thalassemia-major-an-experience-from-north-india
#18
Nupur Parakh, Jagdish Chandra, Sunita Sharma, Bhavna Dhingra, Rajesh Jain, DeoNath Mahto
OBJECTIVE: A combination of desferrioxamine with either deferiprone (DFP) or deferasirox (DFX) for patients with β-thalassemia major who do not achieve negative iron balance with monotherapy has been studied widely. However, poor compliance resulting from the need for parentral administration of desferrioxamine and its cost necessicitates combining 2 oral chelators. METHODS: A prospective study was conducted in patients with transfusion-dependent β-thalassemia major in a tertiary care center over 2 years...
April 2017: Journal of Pediatric Hematology/oncology
https://www.readbyqxmd.com/read/28185140/cost-utility-analysis-of-three-iron-chelators-used-in-monotherapy-for-the-treatment-of-chronic-iron-overload-in-%C3%AE-thalassaemia-major-patients-an-italian-perspective
#19
Alessia Pepe, Giuseppe Rossi, Anthony Bentley, Maria Caterina Putti, Ludovica Frizziero, Domenico Giuseppe D'Ascola, Liana Cuccia, Anna Spasiano, Aldo Filosa, Vincenzo Caruso, Aishah Hanif, Antonella Meloni
PURPOSE: Deferiprone (DFP), deferasirox (DFX) and deferoxamine (DFO) are used in thalassaemia major (TM) patients to treat chronic iron overload. We evaluated the cost-effectiveness of DFP, compared with DFX and DFO monotherapy, from an Italian healthcare system perspective. METHODS: A Markov model was used over a time horizon of 5 years. Italian-specific cost data were combined with Italian efficacy data. Costs and quality-adjusted life years (QALYs) were calculated for each treatment, with cost-effectiveness expressed as cost per QALY...
May 2017: Clinical Drug Investigation
https://www.readbyqxmd.com/read/28142202/new-film-coated-tablet-formulation-of-deferasirox-is-well-tolerated-in-patients-with-thalassemia-or-lower-risk-mds-results-of-the-randomized-phase-ii-eclipse-study
#20
RANDOMIZED CONTROLLED TRIAL
Ali T Taher, Raffaella Origa, Silverio Perrotta, Alexandra Kourakli, Giovan Battista Ruffo, Antonis Kattamis, Ai-Sim Goh, Annelore Cortoos, Vicky Huang, Marine Weill, Raquel Merino Herranz, John B Porter
Once-daily deferasirox dispersible tablets (DT) have a well-defined safety and efficacy profile and, compared with parenteral deferoxamine, provide greater patient adherence, satisfaction, and quality of life. However, barriers still exist to optimal adherence, including gastrointestinal tolerability and palatability, leading to development of a new film-coated tablet (FCT) formulation that can be swallowed with a light meal, without the need to disperse into a suspension prior to consumption. The randomized, open-label, phase II ECLIPSE study evaluated the safety of deferasirox DT and FCT formulations over 24 weeks in chelation-naïve or pre-treated patients aged ≥10 years, with transfusion-dependent thalassemia or IPSS-R very-low-, low-, or intermediate-risk myelodysplastic syndromes...
May 2017: American Journal of Hematology
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