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Hung-Ju Lin, Kun-Pin Hsieh, Shyh-Shin Chiou, Hwang-Shang Kou, Shou-Mei Wu
A field-amplified sample stacking-sweeping micellar electrokinetic chromatography with short-end injection was established for determination of deferasirox (DFX) in plasma. DFX was extracted from plasma and reconstituted with deionized water (lower conductivity solution). Capillary (effective length, 10cm) was filled with background electrolyte (40mM phosphate buffer, pH 4.5, containing 20% methanol). After sample loading from outlet end at 5psi for 15s, separation was carried out by applying high voltage at 15kV for 10min...
November 30, 2016: Journal of Pharmaceutical and Biomedical Analysis
Sarah Allegra, Silvia De Francia, Jessica Cusato, Elisa Pirro, Davide Massano, Antonio Piga, Antonio D'Avolio
OBJECTIVES: Deferasirox adverse effects include the following: gastrointestinal disturbance, mild elevations in serum creatinine levels and intermittent proteinuria; these events are dose-dependent and reversible with drug discontinuation, but this solution can lead to an inadequate iron chelation. For these reasons, interindividual variability of drug plasma concentration could help the clinical management of deferasirox dosage. We sought to describe deferasirox plasma exposure in a cohort of 60 adult patients...
September 27, 2016: Journal of Pharmacy and Pharmacology
Taro Takami, Takahiro Yamasaki, Issei Saeki, Toshihiko Matsumoto, Yutaka Suehiro, Isao Sakaida
Hepatocellular carcinoma (HCC) is one of the deadliest cancers in the world and is associated with a high risk of recurrence. The development of a wide range of new therapies is therefore essential. In this study, from the perspective of supportive therapy for the prevention of HCC recurrence and preservation of liver function in HCC patients, we surveyed a variety of different therapeutic agents. We show that branched chain amino acids (BCAA) supplementation and late evening snack with BCAA, strategies that address issues of protein-energy malnutrition, are important for liver cirrhotic patients with HCC...
August 28, 2016: World Journal of Gastroenterology: WJG
Hadeel A-I Abdul-Zahra, Mea'ad K Hassan, Bahaa A A H Ahmed
Few studies have investigated the quality of life of children with thalassemia in the Middle East or Mediterranean region, especially Iraq. Therefore, this study was performed to assess the health-related quality of life (HRQoL) of patients with β-thalassemia major compared with healthy children and adolescents in the same age group and to evaluate the effects of different iron chelators on HRQoL measurements. A case-control study was performed on patients with β-thalassemia major registered at the Center for Hereditary Blood Diseases in Basra from February 2012 through July 2013...
October 2016: Journal of Pediatric Hematology/oncology
Yusuke Kamihara, Kohichi Takada, Tsutomu Sato, Yutaka Kawano, Kazuyuki Murase, Yohei Arihara, Shohei Kikuchi, Naotaka Hayasaka, Makoto Usami, Satoshi Iyama, Koji Miyanishi, Yasushi Sato, Masayoshi Kobune, Junji Kato
Deregulated iron metabolism underlies the pathogenesis of many human cancers. Recently, low expression of ferroportin, which is the only identified non-heme iron exporter, has been associated with significantly reduced overall survival in multiple myeloma (MM); however, the altered iron metabolism in MM biology remains unclear. In this study we demonstrated, by live cell imaging, that MM cells have increased intracellular iron levels as compared with normal cells. In experiments to test the effect of iron chelation on the growth of MM cells, we found that deferasirox (DFX), an oral iron chelator used to treat iron overload in clinical practice, inhibits MM cell growth both in vivo and in vitro...
September 2, 2016: Oncotarget
Ampaiwan Chuansumrit, Jiraporn Laothamathat, Nongnuch Sirachainan, Witaya Sungkarat, Pakawan Wongwerawattanakoon, Patrapop Kumkrua
BACKGROUND: MRI imaging is an alternative to serum ferritin for assessing iron overload in patients with thalassaemia disease. AIMS: To correlate liver iron concentration (LIC) determined by MRI and clinical and biochemical parameters. METHODS: An MRI study using cardiovascular magnetic resonance (CMR) tools to determine cardiac and liver iron was undertaken in adolescents with thalassaemia disease. RESULTS: Eighty-nine patients (48 males) with thalassaemia disease were enrolled...
August 2016: Paediatrics and International Child Health
Jehn-Chuan Lee, Kun-Chun Chiang, Tsui-Hsia Feng, Yu-Jen Chen, Sung-Ting Chuang, Ke-Hung Tsui, Li-Chuan Chung, Horng-Heng Juang
Oral squamous cell carcinoma (OSCC) is a common malignancy with a growing worldwide incidence and prevalence. The N-myc downstream regulated gene (NDRG) family of NDRG1, 2, 3, and mammary serine protease inhibitor (Maspin) gene are well-known modulators in the neoplasia process. Current research has considered iron chelators as new anti-cancer agents; however, the anticancer activities of iron chelators and their target genes in OSCC have not been well investigated. We showed that iron chelators (Dp44mT, desferrioxamine (DFO), and deferasirox) all significantly inhibit SAS cell growth...
2016: International Journal of Molecular Sciences
Hirofumi Harima, Seiji Kaino, Taro Takami, Shuhei Shinoda, Toshihiko Matsumoto, Koichi Fujisawa, Naoki Yamamoto, Takahiro Yamasaki, Isao Sakaida
BACKGROUND: Iron is essential for cell replication, metabolism and growth. Because neoplastic cells have high iron requirements due to their rapid proliferation, iron depletion may be a novel therapeutic strategy for cancer. Deferasirox (DFX), a novel oral iron chelator, has been successful in clinical trials in iron-overload patients and has been expected to become an anticancer agent. However, no studies have investigated the effects of DFX on pancreatic cancer. This study aimed to elucidate the effects of DFX against pancreatic cancer...
2016: BMC Cancer
Adlette Inati, Mario Kahale, Nada Sbeiti, Maria Domenica Cappellini, Ali T Taher, Suzanne Koussa, Therese A Nasr, Khaled M Musallam, Hussein A Abbas, John B Porter
BACKGROUND: Iron overload is well documented in patients with β-thalassemia major, and patients who have undergone hematopoietic stem cell transplantation (HSCT) remain at risk as a result of pre- and immediate post-HSCT transfusions. PROCEDURE: This is a prospective, randomized, 1-year clinical trial that compares the efficacy and safety of the once-daily oral iron chelator deferasirox versus phlebotomy for the treatment of iron overload in children with β-thalassemia major following HSCT...
August 31, 2016: Pediatric Blood & Cancer
Mehran Karimi, Abbas Avazpour, Sezaneh Haghpanah, Foroogh Toosi, Arash Badie
BACKGROUND: β-thalassemia is the most common heredity disease in Iran. Regular blood transfusion is critical to sustain life and normal growth. Deferasirox is an oral chelator. One of the side effects of the deferasirox is proteinuria. OBJECTIVES: This study aimed to investigate the safety of deferasirox on kidney function in diabetic and nondiabetic β-thalassemia major patients. MATERIALS AND METHODS: In this cross-sectional study, 34 diabetic and 36 nondiabetic patients who take deferasirox (Exjade) 20 to 40 mg/kg/d were studied...
August 19, 2016: Journal of Pediatric Hematology/oncology
Mélodie Aubart, Phalla Ou, Caroline Elie, Carla Canniffe, Shelby Kutty, Vincent Delos, Christine Graffigne, Mariane de Montalembert, Valentine Brousse
Iron overload is an ineluctable complication in chronically transfused children warranting accurate assessment to avoid related morbidity. We investigated longitudinally the relationships between ferritin levels and hepatic and cardiac T2* magnetic resonance imaging (MRI) in a cohort of chronically transfused children receiving chelation therapy. Thirty children with sickle cell anemia (SCA) and 7 with thalassemia major (TM) chelated similarly by deferasirox were analyzed. Sex ratio, age, median duration of transfusion programs (5 y; range, 2 to 14 y), median transfusion iron intake 0...
October 2016: Journal of Pediatric Hematology/oncology
P Joy Ho, Lay Tay, Juliana Teo, Paula Marlton, Andrew Grigg, Tim St Pierre, Greg Brown, Caro-Anne Badcock, Robert Traficante, Othon L Gervasio, Donald K Bowden
OBJECTIVES: To assess the effect of iron chelation therapy with deferasirox on cardiac iron and function in patients with transfusion-dependent thalassemia major, sickle cell disease (SCD), and myelodysplastic syndromes (MDS). METHODS: This phase IV, single-arm, open-label study over 53 wk evaluated the change in cardiac and liver iron load with deferasirox (up to 40 mg/kg/d), measured by magnetic resonance imaging (MRI). RESULTS: Cardiac iron load (myocardial T2*) significantly improved (P = 0...
August 18, 2016: European Journal of Haematology
Seishi Nishitani, Kazuhiro Noma, Toshiaki Ohara, Yasuko Tomono, Shinichiro Watanabe, Hiroshi Tazawa, Yasuhiro Shirakawa, Toshiyoshi Fujiwara
Esophageal carcinomas often have a poor prognosis due to early lymph node metastasis. Epithelial-mesenchymal transition (EMT) is strongly associated with the acquisition of cancer metastasis and invasion. However, there is no established treatment to eliminate the EMT of cancer cells. Iron is an essential element for both normal and cancer cells in humans. Recently, iron depletion has been discovered to suppress tumor growth. Therefore, we hypothesized that decreased iron conditions would regulate EMT phenotypes, as well as suppressing tumor growth...
October 2016: International Journal of Oncology
Harald-Robert Bruch, Yves Dencausse, Jörg Heßling, Gerlinde Michl, Rudolf Schlag, Alexandra Skorupa, Cornelia Schneider-Schranz, Sebastian Wolf, Clemens Schulte, Hans Tesch
BACKGROUND: The non-interventional study CONIFER was designed to assess the safety and clinical practicability of deferasirox for the treatment of transfusional iron overload in myelodysplastic syndrome (MDS) patients. METHODS: Patients included in the study were diagnosed with MDS and received at least 1 treatment with deferasirox. The observation period covered the time from the initial visit until the last follow-up. RESULTS: The data of 99 patients with MDS scored mainly as International Prognostic Scoring System (IPSS) low and intermediate 1 were evaluated...
2016: Oncology Research and Treatment
Archie Ramaswami, Danya J Rosen, Jaime Chu, Birte Wistinghausen, Ronen Arnon
Deferesirox (DFX), an oral chelating agent, is used to treat chronic iron overload in several hematological diseases such as β-thalassemia, sickle cell disease, and myelodysplastic anemia. DFX is generally well tolerated with the exception of gastrointestinal disturbances and rash, although cases of renal toxicity, as well as acute and chronic liver failure, have been reported in adults and children. Here we describe a 3-year-old girl with β-thalassemia undergoing treatment with DFX who presented with acute liver failure and Fanconi's syndrome...
July 29, 2016: Journal of Pediatric Hematology/oncology
Yu-Wen Lai, Leona T Campbell, Marc R Wilkins, Chi Nam Ignatius Pang, Sharon Chen, Dee A Carter
Fungal infections remain very difficult to treat, and developing new antifungal drugs is difficult and expensive. Recent approaches therefore seek to augment existing antifungals with synergistic agents that can lower the therapeutic dose, increase efficacy and prevent resistance from developing. Iron limitation can inhibit microbial growth, and iron chelators have been employed to treat fungal infections. In this study, chequerboard testing was used to explore combinations of iron chelators with antifungal agents against pathogenic Cryptococcus spp...
October 2016: International Journal of Antimicrobial Agents
Suwakon Wongjaikam, Sirinart Kumfu, Juthamas Khamseekaew, Jirapas Sripetchwandee, Somdet Srichairatanakool, Suthat Fucharoen, Siriporn C Chattipakorn, Nipon Chattipakorn
BACKGROUND: Iron chelators are used to treat iron overload cardiomyopathy patients. However, a direct comparison of the benefits of three common iron chelators (deferoxamine (DFO), deferiprone (DFP) and deferasirox (DFX)) or an antioxidant (N-acetyl cysteine (NAC)) with a combined DFP and NAC treatments on left ventricular (LV) function with iron overload has not been investigated. METHODS AND FINDINGS: Male Wistar rats were fed with either a normal diet or a high iron diet (HFe group) for 4 months...
2016: PloS One
Jirapas Sripetchwandee, Suwakon Wongjaikam, Warunsorn Krintratun, Nipon Chattipakorn, Siriporn C Chattipakorn
Iron-overload can cause cognitive impairment due to blood-brain barrier (BBB) breakdown and brain mitochondrial dysfunction. Although deferiprone (DFP) has been shown to exert neuroprotection, the head-to-head comparison among iron chelators used clinically on brain iron-overload has not been investigated. Moreover, since antioxidant has been shown to be beneficial in iron-overload condition, its combined effect with iron chelator has not been tested. Therefore, the hypothesis is that all chelators provide neuroprotection under iron-overload condition, and that a combination of an iron chelator with an antioxidant has greater efficacy than monotherapy...
September 22, 2016: Neuroscience
Mohamed Abdel Malik Hassan, Omar Atef Tolba
INTRODUCTION: Iron overload is the primary cause of mortality and morbidity in thalassemia major (TM) despite advances in chelation therapy. The aim of this study was to compare the effectiveness and safety of deferasirox (DFX) and deferoxamine (DFO) as iron-chelating agents in patients with transfusion-dependent β-thalassemia major. METHODS: This prospective randomized study included 60 patients with transfusion-dependent β-TM during the period from September 2014 to September 2015...
May 2016: Electronic Physician
Maciej W Garbowski, Yongmin Ma, Suthat Fucharoen, Somdet Srichairatanakool, Robert Hider, John B Porter
Nontransferrin-bound iron (NTBI) is a heterogeneously speciated plasma iron, typically detectable when transferrin saturation (TfSat) exceeds 75%. Here, we examine factors affecting NTBI levels by a recently discovered direct chelator-based (CP851) fluorescent bead-linked flow-cytometric assay (bead-NTBI), compared with the established indirect nitrilotriacetate (NTA) assay in 122 iron-overloaded patients, including 64 on recent iron chelation therapy and 13 healthy volunteers. Both methods correlated (r = 0...
June 7, 2016: Translational Research: the Journal of Laboratory and Clinical Medicine
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