DOCSLIB.ORG

Combination of Aclarubicin and Etoposide for the Treatment of Advanced Acute Myeloid Leukemia: Results of a Prospective Multicenter Phase II Trial

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Combination of Aclarubicin and Etoposide for the Treatment of Advanced Acute Myeloid Leukemia: Results of a Prospective Multicenter Phase II Trial Leukemia (1998) 12, 1522–1526 1998 Stockton Press All rights reserved 0887-6924/98 $12.00 http://www.stockton-press.co.uk/leu Combination of aclarubicin and etoposide for the treatment of advanced acute myeloid leukemia: results of a prospective multicenter phase II trial W Kern1, J Braess1, A Grote-Metke2, H Kuse3, R Fuchs4, DK Hossfeld5, A Reichle6,BWo¨rmann1,TBu¨chner7 and W Hiddemann1 for the German AML Cooperative Group 1Department of Hematology and Oncology, Georg-August-University, Go¨ttingen; 2Department of Internal Medicine, Evangelisches Krankenhaus, Hamm; 3Krankenhaus St Georg, Hamburg; 4Department of Internal Medicine, St Antonius Hospital, Eschweiler; 5Department of Hematology and Oncology, Universita¨tsklinikum Eppendorf, Hamburg; 6Department of Hematology and Oncology, University of Regensburg; and 7Department of Hematology and Oncology, University of Mu¨nster, Germany In order to develop new strategies for the treatment of relapsed Patients and methods or refractory acute myeloid leukemia, the German AML Co- operative Group performed a prospective multicenter phase II study to evaluate the antileukemic efficacy of aclarubicin Patients 60 mg/m2/day and etoposide 100 mg/m2/day each given for 5 days. Of 37 heavily pretreated evaluable patients (median age Consecutive patients at ages 18 or older with AML refractory 42 years, range 18–81) 15 (40%) achieved a remission after one to a first salvage attempt or with second or subsequent or two courses of treatment consisting of nine complete (24%) relapses who were admitted at the participating centers and six partial remissions (16%). Fourteen (38%) cases were between August 1988 and November 1990 were eligible for non-responders and eight (22%) patients suffered from early the study. The diagnosis of AML was based on the revised deaths. Disease-free survival for patients in remission and 14 overall survival were 3.2 months each. The median duration of French–American–British (FAB) Group criteria. critical neutropenia Ͻ500/␮l was 27 days. The most frequent All patients were recruited from the first and second line non-hematologic side-effects were stomatitis (WHO III/IV, 48%), trials of the German AML Cooperative Group and the South infections (40%), nausea/vomiting (26%) and diarrhea (24%). German Hemoblastosis Group and had thus received a stan- Cardiac toxicity was mild. This study suggests a substantial dardized prior treatment. First-line therapy consisted of con- antileukemic efficacy and an acceptable toxicity of aclarubicin in combination with etoposide in heavily pretreated patients ventional induction therapy with either TAD-9 (thioguanine, with advanced acute myeloid leukemia, and warrants further cytosine arabinoside, daunorubicin) or DAV (daunorubicin, evaluations in a more favorable stage of the disease. cytosine arabinoside, etoposide), or double induction with Keywords: acute myeloid leukemia; aclarubicin; etoposide; refrac- either TAD-9/TAD-9, DAV/DAV or TAD-9/HAM (high-dose tory disease cytosine arabinoside and mitoxantrone). A second course of induction therapy was applied to patients older than 60 years only upon inadequate response to the first TAD-9 or DAV Introduction cycle. Patients of all ages who achieved a complete remission subsequently received TAD-9 or DAV for consolidation and Although long-term remissions can be achieved in approxi- monthly maintenance therapy for 3 years.15–17 Second-line mately one-third of patients with acute myeloid leukemia treatment consisted of TAD-9 or the sequential high-dose (AML), mostly by combinations of an anthracycline with stan- cytosine arabinoside and mitoxantrone regimen (S-HAM).4 dard- or high-dose cytosine arabinoside,1,2 the majority of Patients with antecedent hematologic disorders, secondary patients experience a relapse and ultimately die from resistant leukemias, and a preceding autologous or allogeneic bone and progressive disease.3–5 New treatment modalities are marrow transplantation were excluded from the study. Further therefore needed to improve the long-term perspectives for exclusion criteria comprised coronary heart disease, heart fail- adult patients with AML. Non-cross-resistant drug combi- ure, cardiomyopathy, severe arterial hypertension, abnormal nations may complement established regimens and may sup- liver function tests (aspartate aminotransferase (AST), alanine port this goal. aminotransferase (ALT) or alkaline phosphatase (AP) more Exhibiting relatively low levels of cross-resistance with than three times the upper normal limits, total bilirubin doxorubicin and daunorubicin,6,7 aclarubicin is a promising Ͼ2.0 mg/dl), impaired renal function (serum creatinine alternative to older anthracyclines and may be less hampered Ͼ2.0 mg/dl), severe infections, or pregnancy. in impairing cytotoxicity by the expression of p-glyco- protein.8,9 The topoisomerase-II inhibitor etoposide reveals substantial antileukemic efficacy as single agent with only lim- Antileukemic therapy ited toxicity10,11 and is rarely used in first-line treatment. Stimulated by promising reports by Rowe et al12 and prelimi- Patients meeting the entry criteria were enrolled in the study nary first own results,13 the German AML Cooperative Group and were treated with aclarubicin 60 mg/m2/day and etopo- initiated a prospective multicenter phase II study to evaluate side 100 mg/m2/day as a 30-min infusion on days 1–5, the antileukemic potential of combination therapy with respectively. Patients not achieving a complete or partial aclarubicin and etoposide in patients with advanced heavily remission by the first course could receive a second course of pretreated AML. the identical regimen. Study parameters Correspondence: W Hiddemann, Georg-August-University, Depart- ment of Hematology and Oncology, Robert-Koch-Straße 40, 37075 Go¨ttingen, Germany; Fax: 49 551 39 2914 Response to therapy was assessed according to CALGB cri- Received 3 April 1998; accepted 23 June 1998 teria.18 Complete remission (CR) was defined as a normal Aclarubicin and etoposide for advanced AML W Kern et al 1523 cellular bone marrow with normal erythroid and myeloid Table 1). All patients had received prior chemotherapy for elements and less than 5% myeloblasts, and with peripheral their disease as indicated above. Twenty-seven (73%) patients blood counts of more than 100 000/␮l platelets and more than had received consolidation treatment with either TAD-9 or 1500/␮l granulocytes for at least 4 weeks. Patients with regen- DAV. Thirty-two (86%) patients had received high-dose cyto- erated peripheral blood values but more than 5% and less sine arabinoside as part of induction therapy or second-line than 25% myeloblasts were considered to be in partial treatment. Overall, 10 (27%) patients had disease refractory to remission (PR), as were patients fulfilling the bone marrow second-line therapy and 27 (73%) had second or subsequent criteria of CR but without full recovery of peripheral blood relapses. AML subtypes were predominantly M1, M2, M4 and platelet and/or white blood cell counts. Patients with per- M5. Thirty-two patients received one course of aclarubicin sisting leukemic blasts in the bone marrow or blood or with and etoposide and five patients received two courses. leukemic regrowth within 4 weeks after initial response were considered as non-responders (NR). Patients dying within 6 weeks after the start of antileukemic therapy without evidence Antileukemic activity of leukemic regrowth were classified as early deaths (ED). The duration of critical cytopenia was evaluated by the time Overall, 15 (40%) patients achieved a remission consisting of for granulocyte recovery to more than 500/␮l and platelet nine complete (24%) and six partial remissions (16%). An recovery to more than 20 000/␮l from the onset of chemo- adequate reduction of bone marrow blasts was documented therapy. The time to CR was measured from the onset of treat- in 13 of 22 (59%) patients with evaluable bone marrow exam- ment to the date of documented CR and disease-free survival inations on day 12, ie 1 week after completion therapy. Four- from the date of documented CR to relapse or death during teen (38%) cases were non-responders and eight (22%) remission. Survival and time to treatment failure were meas- patients suffered from ED (Table 2). Within the group of ured by the time from the beginning of treatment to death, patients with second or subsequent relapses, nine (30%) and documentation of persisting leukemia or relapse, respectively. two (7%) patients achieved a CR and PR, respectively, while Toxicity was evaluated according to the World Health Organization (WHO) grading system.19 In all patients, clinical examinations and ECGs were performed before and 3 weeks Table 1 Patient characteristics after each cycle of chemotherapy, supplemented by ultra- sound cardiography in some cases. n = 37 Sex Statistics male 17 female 20 The primary study end point was the rate of complete and Age (years) partial remissions achieved by one or two courses of chemo- median 42 therapy with aclarubicin and etoposide in a group of 35 evalu- range 18–81 able consecutive patients with advanced AML. A remission FAB rate of more than 35% was targeted. Secondary end points M0 1 (3%) were the duration of disease-free survival in patients achieving M1 10 (27%) a complete or partial remission, the hematologic and non- M2 6 (16%) M4 13 (35%) hematologic toxicity of the regimen, and the rate of ED and M5 5 (14%) NR. An ED rate of less than 30% was targeted. Actuarial ND 2 (5%) values for survival, disease-free survival, time to treatment fail- Prior first-line therapy ure, duration of neutropenia, and time to CR were calculated TAD-9/TAD-9 19 from Kaplan–Meier estimates. TAD-9/HAM 8 DAV/DAV 6 TAD-9 2 S-HAM 1 Study conduct unknown 1 Consolidation (TAD-9 or DAV) 27 (73%) Prior to therapy all patients gave their informed consent for Prior second-line therapy S-HAM 28 participation in the current evaluation after having been TAD-9 2 advised about the purpose and investigational nature of the HAM 2 study as well as of potential risks.
Load more

Recommended publications
  • Transcatheter Arterial Chemoembolization Therapy for Hepatocellular Carcinoma Using Polylactic Acid Microspheres Containing Acla
    [CANCER RESEARCH 49. 4357-4362, August 1. 1989] Transcatheter Arterial Chemoembolization Therapy for Hepatocellular Carcinoma Using Polylactic Acid Microspheres Containing Aclarubicin Hydrochloride 1omonimi Ichihara,1 Kiyoshi Sakamoto, Katsutaka Mori, and Masanobu Akagi Department of Surgery II, Kumamoto University Medical School, Kumamoto 860, Japan 4BSTRACT MATERIALS AND METHODS Transcatheter arterial Chemoembolization therapy using polylactic Preparation of PLA-ACRms acid microspheres containing aclarubicin hydrochloride (ACR) was per PLA-ACRms were prepared in the pharmacy of the Kumamoto formed in 62 patients with primary hepatocellular carcinoma. These microspheres were about 200 ¡anin diameter and contained 10% (w/w) University Hospital. Briefly, aclarubicin hydrochloride and isopropyl aclarubicin. A single dose of polylactic acid microspheres containing ACR myristate, a medium-chain fatty acid ester, were dissolved in 7.5% (50-100 mg of ACR) was administered 1 to 8 times with a mean of 2.2 polylactic acid-methylene chloride. The resultant solution was dispersed in 1% gelatin solution and sterilized in an autoclave for 20 min at doses (a total of 160 treatments) in 62 patients. Antitumor effects were 120°C;thismixture was then stirred with a magnetic stirrer at 500 rpm observed from the decrease in serum a-fetoprotein levels (82.1% of the patients) and in two dimensional size of tumor on computed tomography for 1 h. The resultant microspheres were collected by filtration through (93.6%). The cumulative survival rate was 54.3% at 1 year, 24.6% at 2 a membrane filter (3 //m pore diameter), rinsed 2 to 3 times (in 1 liter years, and 19.2% at 3 years, respectively, among 59 patients with of distilled water), and dried under reduced pressure for 5 days.
    [Show full text]
  • Phenotype Microarrays Panels PM-M1 to PM-M14
    Phenotype MicroArrays™ Panels PM-M1 to PM-M14 for Phenotypic Characterization of Mammalian Cells Assays: Energy Metabolism Pathways Ion and Hormone Effects on Cells Sensitivity to Anti-Cancer Agents and for Optimizing Culture Conditions for Mammalian Cells PRODUCT DESCRIPTIONS AND INSTRUCTIONS FOR USE PM-M1 Cat. #13101 PM-M2 Cat. #13102 PM-M3 Cat. #13103 PM-M4 Cat. #13104 PM-M5 Cat. #13105 PM-M6 Cat. #13106 PM-M7 Cat. #13107 PM-M8 Cat. #13108 PM-M11 Cat. #13111 PM-M12 Cat. #13112 PM-M13 Cat. #13113 PM-M14 Cat. #13114 © 2016 Biolog, Inc. All rights reserved Printed in the United States of America 00P 134 Rev F February 2020 - 1 - CONTENTS I. Introduction ...................................................................................................... 2 a. Overview ................................................................................................... 2 b. Background ............................................................................................... 2 c. Uses ........................................................................................................... 2 d. Advantages ................................................................................................ 3 II. Product Description, PM-M1 to M4 ................................................................ 3 III. Protocols, PM-M1 to M4 ................................................................................. 7 a. Materials Required .................................................................................... 7 b. Determination
    [Show full text]
  • Towards the Reduction of Occupational Exposure To
    TOWARDS THE REDUCTION OF OCCUPATIONAL EXPOSURE TO CYTOTOXIC DRUGS by Cristian Vasile Barzan B.Sc. Simon Fraser University, 2007 A THESIS SUBMITTED IN PARTIAL FULFILLMENT OF THE REQUIRMENTS FOR THE DEGREE OF MASTER OF SCIENCE in The Faculty of Graduate Studies (Occupational and Environmental Hygiene) THE UNIVERSITY OF BRITISH COLUMBIA (Vancouver) October 2010 © Cristian Vasile Barzan, 2010 Abstract Background : One of the most powerful and widely used techniques in cancer treatment is the use of cytotoxic drugs in chemotherapy. These drugs are inherently hazardous with many of them causing carcinogenic, mutagenic or teratogenic health outcomes. Occupational exposure to cytotoxic drugs is of great concern due to their lack of selectivity between healthy and unhealthy cells. Widespread cytotoxic drug contamination has been reported in North America, Europe and Australia. Current cleaning protocols for hazardous antineoplastic drugs include the use of disinfectants and oxidizing agents, such as household bleach. Aim : The thesis project focused on two objectives: 1) hypothesize and confirm potential hazardous by- products arising from cleaning cyclophosphamide, a widely used cytotoxic drugs, with household bleach, a commonly used cleaning agent; 2) develop an effective and safe cleaning agent for cytotoxic drugs in order to prevent and eliminate exposure to these drugs. Methods : The gas chromatograph mass spectrum (GC/MS) was used to analyze the decomposition of cyclophosphamide by household bleach (5.25% hypochlorite). The reaction was conducted in a test-tube and the by-products extracted and derivatized prior to analysis. Multiple cleaning agent compositions were tested on 10x10cm stainless steel plates spiked with the two model cytotoxic drugs, cyclophosphamide and methotrexate.
    [Show full text]
  • Functional Similarity of Anticancer Drugs by MTT Bioassay
    cer Scien an ce C & f o T l h a e Hiwasa et al., J Cancer Sci Ther 2011, 3.10 n r a Journal of r p u 1000099 y o J DOI: 10.4172/1948-5956. ISSN: 1948-5956 Cancer Science & Therapy Rapid Communication Open Access Functional Similarity of Anticancer Drugs by MTT Bioassay Takaki Hiwasa1*,Takanobu Utsumi1, Mari Yasuraoka1, Nana Hanamura1, Hideaki Shimada2, Hiroshi Nakajima3, Motoo Kitagawa4, Yasuo Iwadate4,5, Ken-ichiro Goto6, Atsushi Takeda7, Kenzo Ohtsuka8, Hiroyoshi Ariga9 and Masaki Takiguchi1 1Department of Biochemistry, and Genetics, Chiba University, Graduate School of Medicine, Chuo-ku, Chiba 260-8670, Japan 2Department of Surgery, School of Medicine, Toho University, Ota-ku, Tokyo 143-8541, Japan 3Department of Molecular Genetics, Chiba University, Graduate School of Medicine, Chuo-ku, Chiba 260-8670, Japan 4Department of Molecular and Tumor Pathology, Chiba University, Graduate School of Medicine, Chuo-ku, Chiba 260-8670, Japan 5Department of Neurological Surgery, Chiba University, Graduate School of Medicine, Chuo-ku, Chiba 260-8670, Japan 6Department of Orthopaedic Surgery, National Hospital Organization, Shimoshizu Hospital, Yotsukaido, Chiba 284-0003, Japan 7Laboratory of Biochemistry, Graduate School of Nutritional Sciences, Sagami Women’s University, Sagamihara, Kanagawa 252-0383, Japan 8Laboratory of Cell & Stress Biology, Department of Environmental Biology, Chubu University, Matsumoto-cho, Kasugai, Aichi 487-8501, Japan 9Graduate School of Pharmaceutical Sciences, Hokkaido University, Kita-ku, Sapporo 060-0812, Japan Abstract We prepared normal or Ha-ras-transformed NIH3T3 cells transfected stably or transiently with various tumor- related genes. The chemosensitivity of the transfected clones to 16 anticancer drugs was compared to the parental control cells using the MTT assay.
    [Show full text]
  • Metabolic Carbonyl Reduction of Anthracyclines — Role in Cardiotoxicity and Cancer Resistance
    Invest New Drugs DOI 10.1007/s10637-017-0443-2 REVIEW Metabolic carbonyl reduction of anthracyclines — role in cardiotoxicity and cancer resistance. Reducing enzymes as putative targets for novel cardioprotective and chemosensitizing agents Kamil Piska1 & Paulina Koczurkiewicz1 & Adam Bucki 2 & Katarzyna Wójcik-Pszczoła1 & Marcin Kołaczkowski2 & Elżbieta Pękala1 Received: 23 November 2016 /Accepted: 17 February 2017 # The Author(s) 2017. This article is published with open access at Springerlink.com Summary Anthracycline antibiotics (ANT), such as doxoru- monoHER, curcumin, (−)-epigallocatechin gallate, resvera- bicin or daunorubicin, are a class of anticancer drugs that are trol, berberine or pixantrone, and their modulating effect on widely used in oncology. Although highly effective in cancer the activity of ANT is characterized and discussed as potential therapy, their usefulness is greatly limited by their mechanism of action for novel therapeutics in cancer cardiotoxicity. Possible mechanisms of ANT cardiotoxicity treatment. include their conversion to secondary alcohol metabolites (i.e. doxorubicinol, daunorubicinol) catalyzed by carbonyl re- Keywords Anthracyclines . Cardiotoxicity . Resistance . ductases (CBR) and aldo-keto reductases (AKR). These me- Pharmacokinetics . Drug metabolism . Anticancer agents tabolites are suspected to be more cardiotoxic than their parent compounds. Moreover, overexpression of ANT-reducing en- zymes (CBR and AKR) are found in many ANT-resistant Introduction cancers. The secondary metabolites show decreased cytotoxic properties and are more susceptible to ABC-mediated efflux Anthracyclines (ANT) are a class of cell-cycle non-specific than their parent compounds; thus, metabolite formation is anticancer antibiotics that were first isolated from the considered one of the mechanisms of cancer resistance. Streptomyces genus in the early 1960s.
    [Show full text]
  • In Vitro Synergistic Effects of Anthracycline Antitumor Agents And
    evelo f D pin l o g a D Matsumoto et al., J Develop Drugs 2014, 3:2 n r r u u g o s J Journal of Developing Drugs DOI: 10.4172/2329-6631.1000125 ISSN: 2329-6631 Research Article Open Access In vitro Synergistic Effects of Anthracycline Antitumor Agents and Fluconazole Against Azole-Resistant Candida albicans Clinical Isolates Matsumoto S, Kurakado S, Shiokama T, Ando Y, Aoki N, Cho O and Sugita T* Department of Microbiology, Meiji Pharmaceutical University, Kiyose, Tokyo Japan Abstract The number of azole-resistant Candida albicans clinical isolates is increasing. This study searched for compounds that are functionally synergistic with fluconazole against azole-resistant C. albicans strains. Synergistic effects were evaluated using the checkerboard method in a time-kill study using anthracycline antitumor agents and azole-resistant C. albicans strains. Of the five anthracycline agents examined, aclarubicin by itself had antifungal effects, whereas daunorubicin, doxorubicin, epirubicin, and idarubicin did not show antifungal effects alone, but did exert dose- and time- dependent synergistic effects with fluconazole against the C. albicans strains. No antitumor agent other than anthracycline exhibited an anti-Candida effect. Anthracycline compounds may therefore be useful as seeds for development of new antifungal agents. Keywords: Anthracycline; antitumor agent; azole-resistant Candida Materials and Methods albicans; synergy Strains used Introduction Twelve azole-resistant Candida albicans strains obtained from Candida albicans is the most frequently observed opportunistic patients’ blood were examined in this study. All strains were cultured fungal pathogen and causes deep-seated fungal infection, mainly on Sabouraud dextrose agar (SDA) plates at 37°C.
    [Show full text]
  • Successful Treatment of a Patient with Synchronous Advanced Non-Small
    ANTICANCER RESEARCH 25: 2579-2582 (2005) Successful Treatment of a Patient with Synchronous Advanced Non-small Cell Lung Cancer and Acute Myeloid Leukemia by a Combination of Gefitinib, Low-dose Cytarabine and Aclarubicin NAGIO TAKIGAWA1, MAKOTO TAKEUCHI2, TAKUO SHIBAYAMA1, ISAO YOSHIDA2, NORIKO KAWATA1, ATSUHIKO TADA1, HIROSHI UEOKA4 and KIYOSHI TAKAHASHI3 1Department of Pulmonary Medicine, 2Department of Hematology and 3Department of Internal Medicine, National Hospital Organization, Minami-Okayama Medical Center, 4066 Hayashima, Okayama 701-0304; 4Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine and Dentistry, 2-5-1 Shikata, Okayama 700-8558, Japan Abstract. There are few reports describing simultaneous not yet been established. Gefitinib, the tyrosine kinase occurrence of acute leukemia and lung cancer. We describe inhibitor of epidermal growth factor receptor, has anti- here an 83-year-old woman who simultaneously developed tumor activity in advanced NSCLC (5, 6), and was effective advanced adenocarcinoma of the lung and acute myeloid even in elderly patients with poor PS (7, 8). On the other leukemia. She could not receive intensive chemotherapy due to hand, for elderly patients with acute myeloid leukemia poor performance status. This patient was treated with a (AML), conventional combinations of anthracycline combination of gefitinib, low-dose cytarabine and aclarubicin. (daunorubicin or idarubicin) and cytarabine have frequently This combination could be safely administered in the elderly been used (9), however, the standard treatment for patients patient with poor performance status and was effective for both aged 75 years or older has not been established (10). In lung cancer and acute myeloid leukemia. Japan, a combination of low-dose cytarabine and aclarubicin was reported to be useful in previously untreated elderly (65 The incidence of lung cancer is increasing worldwide and - 82 years old) patients with AML (11).
    [Show full text]
  • All-Trans Retinoic Acid and Arsenic Trioxide Resistance of Acute Promyelocytic Leukemia with the Variant STAT5B-RARA Fusion Gene
    Letters to the Editor 1606 leukemia mouse model. This effect was proposed to be due, at REFERENCES least in part, to inhibition of FBXW7, a negative regulator of Notch 1 Ferrando AA, Neuberg DS, Staunton J, Loh ML, Huard C, Raimondi SC et al. Gene 8 signaling. However, FBXW7 targets the degradation of other expression signatures define novel oncogenic pathways in T cell acute lympho- oncogenic proteins, such as c-Myc and mTOR, and the expression blastic leukemia. Cancer Cell 2002; 1: 75–87. of miR-223 is significantly elevated in TAL1-positive T-ALL cases 2 Cardoso BA, de Almeida SF, Laranjeira AB, Carmo-Fonseca M, Yunes JA, (Supplementary Figure 2), suggesting that the oncogenic function Coffer PJ et al. TAL1/SCL is downregulated upon histone deacetylase of this microRNA may extend beyond mere collaboration in Notch- inhibition in T-cell acute lymphoblastic leukemia cells. Leukemia 2011; 25: induced leukemia. Moreover, the proleukemic role of mir-223 may 1578–1586. 3 O’Neil J, Shank J, Cusson N, Murre C, Kelliher M. TAL1/SCL induces leukemia be also achieved by downregulating targets such as E2F1, FOXO1, by inhibiting the transcriptional activity of E47/HEB. Cancer Cell 2004; 5: RHOB or EPB41L3, which have been associated with induction of 587–596. apoptosis and/or have tumor-suppressive roles (Supplementary 4 Sanda T, Lawton LN, Barrasa MI, Fan ZP, Kohlhammer H, Gutierrez A et al. Table 5). Interestingly, the intriguing possibility that miR-223 may Core transcriptional regulatory circuit controlled by the TAL1 complex potentially act downstream of TAL1 to negatively regulate MEF2C, in human T cell acute lymphoblastic leukemia.
    [Show full text]
  • Promising Survival for Patients with Glioblastoma Multiforme Treated with Individualised Chemotherapy Based on in Vitro Drug Sensitivity Testing
    British Journal of Cancer (2003) 89, 1896 – 1900 & 2003 Cancer Research UK All rights reserved 0007 – 0920/03 $25.00 www.bjcancer.com Promising survival for patients with glioblastoma multiforme treated with individualised chemotherapy based on in vitro drug sensitivity testing Clinical *,1 2 3 1 Y Iwadate , S Fujimoto , H Namba and A Yamaura 1Department of Neurological Surgery, Graduate School of Medicine, Chiba University, Inohana 1-8-1, Chuo-ku, Chiba 260-8670, Japan; 2Division of 3 Chemotherapy, Chiba Cancer Center, Nitona 666-2, Chuo-ku, Chiba 260-8717, Japan; Department of Neurosurgery, Hamamatsu University School of Medicine, Handayama 1-20-1, Hamamatsu 431-3192, Japan We retrospectively investigated the efficacy and feasibility of individualised chemotherapy based on in vitro drug sensitivity testing (DST) for patients with glioblastoma multiforme. A total of 40 consecutive patients with glioblastoma multiforme (GM) were enrolled into this study between January 1995 and December 2000. The flow cytometric (FCM) detection of apoptosis was used to determine the in vitro sensitivity of tumour cells obtained at surgery to 30 different kinds of anticancer agents. From the results of FCM assay, an in vitro best regimen was prospectively selected. All the patients concurrently received the individualised chemotherapy with the in vitro best regimen and 60 Gy of conventional radiation therapy. Of the 31 assessable patients, eight patients (26%) achieved partial response, and 20 patients (65%) had stable disease. The median survival time was 20.5 months. The individualised chemotherapy based on in vitro DST was associated with favourable survival time for the patients with GM compared with the reported results of conventional therapy regimens.
    [Show full text]
  • Oxidative Stress Involvement in Chemically Induced Differentiation of K562 Cells
    Oxidative stress involvement in chemically induced differentiation of K562 cells. B. Chénais, M. Andriollo, P. Guiraud, R. Belhoussine, P. Jeannesson To cite this version: B. Chénais, M. Andriollo, P. Guiraud, R. Belhoussine, P. Jeannesson. Oxidative stress involvement in chemically induced differentiation of K562 cells.. Free Radical Biology and Medicine, Elsevier, 2000, 28 (1), pp.18-27. hal-00422927 HAL Id: hal-00422927 https://hal.archives-ouvertes.fr/hal-00422927 Submitted on 8 Oct 2009 HAL is a multi-disciplinary open access L’archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destinée au dépôt et à la diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publiés ou non, lished or not. The documents may come from émanant des établissements d’enseignement et de teaching and research institutions in France or recherche français ou étrangers, des laboratoires abroad, or from public or private research centers. publics ou privés. Oxidative stress in K562 cells differentiation 1 OXIDATIVE STRESS INVOLVEMENT IN CHEMICALLY-INDUCED DIFFERENTIATION OF K562 CELLS. Benoît Chénais *, Maud Andriollo †, Pascale Guiraud †, Rajae Belhoussine ‡ and Pierre Jeannesson * * Laboratoire de Biochimie et Biologie Moléculaire, ‡ Laboratoire de Spectroscopie Biomoléculaire, EA2063-MéDIAN, Faculté de Pharmacie, Reims, France and † Laboratoire de Biologie du Stress Oxydant, JE538, Faculté de Pharmacie, Grenoble, France. Acknowledgements - The authors wish to thank Dr MJ Richard for her technical assistance. This work was supported in part by grants from the french Ligue Nationale Contre le Cancer, comités de l’Aisne, des Ardennes et de Haute-Marne. Address correspondence to - Dr. Benoît Chénais, Laboratoire de Biochimie et Biologie Moléculaire, UFR Pharmacie, 51 Rue Cognacq-Jay, F-51096 Reims Cedex, France.
    [Show full text]
  • Experimental Chemotherapy-Induced Skin Necrosis in Swine. Mechanistic Studies of Anthracycline Antibiotic Toxicity and Protection with a Radical Dimer Compound
    Experimental chemotherapy-induced skin necrosis in swine. Mechanistic studies of anthracycline antibiotic toxicity and protection with a radical dimer compound. S D Averbuch, … , T H Koch, N R Bachur J Clin Invest. 1988;81(1):142-148. https://doi.org/10.1172/JCI113285. Research Article The reactivity of antitumor anthracycline and mitomycin C antibiotics with the oxomorpholinyl radical dimers, bi(3,5,5- trimethyl-2-oxomorpholin-3-yl) (TM3) and bi(3,5-dimethyl-5-hydroxymethyl-2-oxomorpholin-3-yl) (DHM3), was studied in vitro. The oxomorpholinyl radical reduced daunorubicin to a quinone methide intermediate that reacted with solvent to form 7-deoxydaunorubicinone. The solvolysis reaction followed first order kinetics, and the reactivity rate constants (k2) measured for seven anthracycline analogues ranged from 2 X 10(-2) s-1 to 8.0 X 10(-4) s-1. The chemical reactivity of each anthracycline quinone methide correlated with the total skin toxicity caused by the respective parent anthracycline following injection into swine skin. Microscopic examination of experimental lesions in swine skin resemble those observed in humans after inadvertant chemotherapy extravasation. Hydrocortisone sodium succinate was not effective for the treatment of doxorubicin-induced skin necrosis, whereas DHM3 was effective for the treatment of skin necrosis caused by all seven anthracyclines and by the quinone containing antibiotic, mitomycin C. Find the latest version: https://jci.me/113285/pdf Experimental Chemotherapy-induced Skin Necrosis in Swine Mechanistic Studies of Anthracycline Antibiotic Toxicity and Protection with a Radical Dimer Compound Steven D. Averbuch, Marybeth Boldt,* Giorgio Gaudiano,* Jere B. Stern, Tad H. Koch,* and Nicholas R.
    [Show full text]
  • Cardiac Toxicity in Breast Cancer Survivors: Review of Potential Cardiac Problems Brian R.J
    Review Cardiac Toxicity in Breast Cancer Survivors: Review of Potential Cardiac Problems Brian R.J. Healey Bird1and Sandra M. Swain2 Abstract As breast cancer survival is increased by the diagnosis of earlier-stage disease and treatments improve, the side effects of cancer treatments, such as cardiotoxicity, remain clinically important. Although physicians have known for 30 years that anthracyclines cause acute and chronic cardio- toxicity, the cardiotoxic effects of radiation therapy, hormonal therapy (including tamoxifen and the aromatase inhibitors), and chemotherapy with taxanes and trastuzumab treatment have emerged more recently. This review examines the cardiac toxicity of adjuvant therapy, monitoring for early changes and existing guidelines for monitoring cardiac function in patients with breast cancer. As methods for detecting and treating breast cancer improve, fraction. Left ventricular dysfunction with normal LVEF is survival of breast cancer patients is increasing but the side commonly called diastolic dysfunction and when accompanied effects of adjuvant breast cancer therapy, including cardiotox- with dyspnea, fatigue, and fluid retention is known as diastolic icity, remain clinically important. A single breast cancer patient heart failure. may receive anthracyclines, trastuzumab, and radiation therapy Anthracyclines are believed to cause immediate damage to before commencing hormonal therapy. We summarize preclin- myocardial cells by free radical generation, although it may take ical and clinical data on incidence, monitoring, and manage- months or years for this damage to become clinically apparent. ment of both acute and chronic cardiac cardiotoxicity in breast Dexrazoxane is used to prevent free radical generation by cancer survivors. This information should assist clinicians in chelating intracellular iron. ACE inhibitors and h-blockers may advising their patients of the risks and benefits of adjuvant delay further expression and slow clinical progression to CHF treatments.
    [Show full text]