Facile Formation of a Crosslinked Adduct Between DNA And
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And Cisplatin-Resistant Ovarian Cancer
Vol. 2, 607–610, July 2003 Molecular Cancer Therapeutics 607 Alchemix: A Novel Alkylating Anthraquinone with Potent Activity against Anthracycline- and Cisplatin-resistant Ovarian Cancer Klaus Pors, Zennia Paniwnyk, mediated stabilization of the topo II-DNA-cleavable complex Paul Teesdale-Spittle,1 Jane A. Plumb, and resulting in inhibition of poststrand passage DNA religa- Elaine Willmore, Caroline A. Austin, and tion (1). This event is not lethal per se but initiates a cascade 2 Laurence H. Patterson of events leading to cell death (2). Anthraquinones, as ex- Department of Pharmaceutical and Biological Chemistry, The School of emplified by mitoxantrone, are topo II inhibitors with proven Pharmacy, University of London, London WC1N 1AX, United Kingdom [K. P., L. H. P.]; Department of Pharmacy, De Montfort University, success for the treatment of advanced breast cancer, non- Leicester LE1 9BH, United Kingdom [Z. P., P. T. S.]; Cancer Research Hodgkin’s lymphoma, and acute leukemia (3). Intercalation is UK Department of Medical Oncology, University of Glasgow, Glasgow a crucial part of topo II inhibition by cytotoxic anthraquinones G61 1BD, United Kingdom [J. A. P.]; and School of Cell and Molecular Biosciences, The Medical School, University of Newcastle upon Tyne, with high affinity for DNA (4). It is likely that the potent Newcastle upon Tyne NE2 4HH, United Kingdom [E. W., C. A. A.] cytotoxicity of anthraquinones is related to their slow rate of dissociation from DNA, the kinetics of which favors long- term trapping of the topo-DNA complexes (5). However, Abstract currently available DNA intercalators at best promote a tran- Chloroethylaminoanthraquinones are described with sient inhibition of topo II, because the topo-drug-DNA ter- intercalating and alkylating capacity that potentially nary complex is reversed by removal of the intracellular drug covalently cross-link topoisomerase II (topo II) to DNA. -
A Comparison of Early Intensive Methotrexate/Mercaptopurine With
Leukemia (2001) 15, 1038–1045 2001 Nature Publishing Group All rights reserved 0887-6924/01 $15.00 www.nature.com/leu A comparison of early intensive methotrexate/mercaptopurine with early intensive alternating combination chemotherapy for high-risk B-precursor acute lymphoblastic leukemia: a Pediatric Oncology Group phase III randomized trial SJ Lauer1, JJ Shuster2, DH Mahoney Jr3, N Winick4, S Toledano5, L Munoz5, G Kiefer6, JD Pullen7, CP Steuber3 and BM Camitta6 1Emory University School of Medicine, Atlanta, GA; 2Pediatric Oncology Group Statistical Office and Department of Statistics, University of Florida, Gainesville, FL; 3Texas Children’s Cancer Center, Baylor College of Medicine, Houston, TX; 4University of Texas Southwestern Medical Center, Dallas, TX; 5University Miami School of Medicine, Miami, FL; 6Midwest Children’s Cancer Center, Milwaukee, WI; and 7University of Mississippi Medical Center Children’s Hospital, Jackson, MS, USA A prospective, randomized multicenter study was performed to to their risk for relapse and treatment strategies designed to evaluate the relative efficacy of two different concepts for early improve event-free survival (EFS). intensive therapy in a randomized trial of children with B-pre- cursor acute lymphoblastic leukemia (ALL) at high risk (HR) for It is believed that the leading causes of relapse in children relapse. Four hundred and ninety eligible children with HR-ALL with higher risk ALL (HR-ALL) are inadequate cell kill and were randomized on the Pediatric Oncology Group (POG) 9006 emergence of drug-resistant clones. Clinical trials using early phase III trial between 7 January 1991 and 12 January 1994. intensive myelosuppressive combination chemotherapy as After prednisone (PDN), vincristine (VCR), asparaginase (ASP) post-induction consolidation were designed to maximize cell and daunorubicin (DNR) induction, 470 patients received either 2 kill and address drug resistance. -
Incidence of Differentiation Syndrome Associated with Treatment
Journal of Clinical Medicine Review Incidence of Differentiation Syndrome Associated with Treatment Regimens in Acute Myeloid Leukemia: A Systematic Review of the Literature Lucia Gasparovic 1, Stefan Weiler 1,2, Lukas Higi 1 and Andrea M. Burden 1,* 1 Institute of Pharmaceutical Sciences, Department of Chemistry and Applied Biosciences, ETH Zurich, 8093 Zurich, Switzerland; [email protected] (L.G.); [email protected] (S.W.); [email protected] (L.H.) 2 National Poisons Information Centre, Tox Info Suisse, Associated Institute of the University of Zurich, 8032 Zurich, Switzerland * Correspondence: [email protected]; Tel.: +41-76-685-22-56 Received: 30 August 2020; Accepted: 14 October 2020; Published: 18 October 2020 Abstract: Differentiation syndrome (DS) is a potentially fatal adverse drug reaction caused by the so-called differentiating agents such as all-trans retinoic acid (ATRA) and arsenic trioxide (ATO), used for remission induction in the treatment of the M3 subtype of acute myeloid leukemia (AML), acute promyelocytic leukemia (APL). However, recent DS reports in trials of isocitrate dehydrogenase (IDH)-inhibitor drugs in patients with IDH-mutated AML have raised concerns. Given the limited knowledge of the incidence of DS with differentiating agents, we conducted a systematic literature review of clinical trials with reports of DS to provide a comprehensive overview of the medications associated with DS. In particular, we focused on the incidence of DS reported among the IDH-inhibitors, compared to existing ATRA and ATO therapies. We identified 44 published articles, encompassing 39 clinical trials, including 6949 patients. Overall, the cumulative incidence of DS across all treatment regimens was 17.7%. -
Contribution to Physico-Chemical Studies of Squalenoylated Nanomedicines for Cancer Treatment Julie Mougin
Contribution to physico-chemical studies of squalenoylated nanomedicines for cancer treatment Julie Mougin To cite this version: Julie Mougin. Contribution to physico-chemical studies of squalenoylated nanomedicines for cancer treatment. Theoretical and/or physical chemistry. Université Paris-Saclay, 2020. English. NNT : 2020UPASS038. tel-02885220 HAL Id: tel-02885220 https://tel.archives-ouvertes.fr/tel-02885220 Submitted on 30 Jun 2020 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. Contribution to physico-chemical studies of squalenoylated nanomedicines for cancer treatment Thèse de doctorat de l'université Paris-Saclay École doctorale n° 569, Innovation thérapeutique : du fondamental à l’appliqué (ITFA) Spécialité de doctorat : Pharmacotechnie et Biopharmacie Unité de recherche : Université Paris-Saclay, CNRS, Institut Galien Paris Sud, 92296, Châtenay-Malabry, France Référent : Faculté de Pharmacie Thèse présentée et soutenue à Châtenay-Malabry, le 28/02/2020, par Julie MOUGIN Composition du Jury Elias FATTAL Président Professeur, Université -
Daunorubicin Hydrochloride Injection Hikma Pharmaceuticals USA Inc
DAUNORUBICIN HYDROCHLORIDE- daunorubicin hydrochloride injection Hikma Pharmaceuticals USA Inc. ---------- DAUNORUBICIN HYDROCHLORIDE INJECTION Rx ONLY WARNINGS 1.Daunorubicin Hydrochloride Injection must be given into a rapidly flowing intravenous infusion. It must never be given by the intramuscular or subcutaneous route. Severe local tissue necrosis will occur if there is extravasation during administration. 2.Myocardial toxicity manifested in its most severe form by potentially fatal congestive heart failure may occur either during therapy or months to years after termination of therapy. The incidence of myocardial toxicity increases after a total cumulative dose exceeding 400 to 550 mg/m2 in adults, 300 mg/m2 in children more than 2 years of age, or 10 mg/kg in children less than 2 years of age. 3.Severe myelosuppression occurs when used in therapeutic doses; this may lead to infection or hemorrhage. 4.It is recommended that daunorubicin hydrochloride be administered only by physicians who are experienced in leukemia chemotherapy and in facilities with laboratory and supportive resources adequate to monitor drug tolerance and protect and maintain a patient compromised by drug toxicity. The physician and institution must be capable of responding rapidly and completely to severe hemorrhagic conditions and/or overwhelming infection. 5.Dosage should be reduced in patients with impaired hepatic or renal function. DESCRIPTION Daunorubicin hydrochloride is the hydrochloride salt of an anthracycline cytotoxic antibiotic produced by a strain of Streptomyces coeruleorubidus. It is provided as a deep red sterile liquid in vials for intravenous administration only. Each mL contains 5 mg daunorubicin (equivalent to 5.34 mg of daunorubicin hydrochloride), 9 mg sodium chloride; sodium hydroxide and/or hydrochloric acid (to adjust pH), and water for injection, q.s. -
5-Fluorouracil + Adriamycin + Cyclophosphamide) Combination in Differentiated H9c2 Cells
Article Doxorubicin Is Key for the Cardiotoxicity of FAC (5-Fluorouracil + Adriamycin + Cyclophosphamide) Combination in Differentiated H9c2 Cells Maria Pereira-Oliveira, Ana Reis-Mendes, Félix Carvalho, Fernando Remião, Maria de Lourdes Bastos and Vera Marisa Costa * UCIBIO, REQUIMTE, Laboratory of Toxicology, Faculty of Pharmacy, University of Porto, Rua de Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugal; [email protected] (M.P.-O.); [email protected] (A.R.-M.); [email protected] (F.C.); [email protected] (F.R.); [email protected] (M.L.B.) * Correspondence: [email protected] Received: 4 October 2018; Accepted: 3 January 2019; Published: 10 January 2019 Abstract: Currently, a common therapeutic approach in cancer treatment encompasses a drug combination to attain an overall better efficacy. Unfortunately, it leads to a higher incidence of severe side effects, namely cardiotoxicity. This work aimed to assess the cytotoxicity of doxorubicin (DOX, also known as Adriamycin), 5-fluorouracil (5-FU), cyclophosphamide (CYA), and their combination (5-Fluorouracil + Adriamycin + Cyclophosphamide, FAC) in H9c2 cardiac cells, for a better understanding of the contribution of each drug to FAC-induced cardiotoxicity. Differentiated H9c2 cells were exposed to pharmacological relevant concentrations of DOX (0.13–5 μM), 5-FU (0.13–5 μM), CYA (0.13–5 μM) for 24 or 48 h. Cells were also exposed to FAC mixtures (0.2, 1 or 5 μM of each drug and 50 μM 5-FU + 1 μM DOX + 50 μM CYA). DOX was the most cytotoxic drug, followed by 5-FU and lastly CYA in both cytotoxicity assays (reduction of 3-(4,5-dimethylthiazol-2- yl)-2,5-diphenyl tetrazolium bromide (MTT) and neutral red (NR) uptake). -
Cardioprotective Effects of Exercise Training on Doxorubicin-Induced
www.nature.com/scientificreports OPEN Cardioprotective efects of exercise training on doxorubicin‑induced cardiomyopathy: a systematic review with meta‑analysis of preclinical studies Paola Victória da Costa Ghignatti, Laura Jesuíno Nogueira, Alexandre Machado Lehnen & Natalia Motta Leguisamo* Doxorubicin (DOX)‑induced cardiotoxicity in chemotherapy is a major treatment drawback. Clinical trials on the cardioprotective efects of exercise in cancer patients have not yet been published. Thus, we conducted a systematic review and meta‑analysis of preclinical studies for to assess the efcacy of exercise training on DOX‑induced cardiomyopathy. We included studies with animal models of DOX‑induced cardiomyopathy and exercise training from PubMed, Web of Sciences and Scopus databases. The outcome was the mean diference (MD) in fractional shortening (FS, %) assessed by echocardiography between sedentary and trained DOX‑treated animals. Trained DOX‑treated animals improved 7.40% (95% CI 5.75–9.05, p < 0.001) in FS vs. sedentary animals. Subgroup analyses revealed a superior efect of exercise training execution prior to DOX exposure (MD = 8.20, 95% CI 6.27–10.13, p = 0.010). The assessment of cardiac function up to 10 days after DOX exposure and completion of exercise protocol was also associated with superior efect size in FS (MD = 7.89, 95% CI 6.11–9.67, p = 0.020) vs. an echocardiography after over 4 weeks. Modality and duration of exercise, gender and cumulative DOX dose did were not individually associated with changes on FS. Exercise training is a cardioprotective approach in rodent models of DOX‑induced cardiomyopathy. Exercise prior to DOX exposure exerts greater efect sizes on FS preservation. -
Comparison of the Interaction of Doxorubicin, Daunorubicin, Idarubicin and Idarubicinol with Large Unilamellar Vesicles Circular Dichroism Study
Biochimica et Biophysica Acta 1370Ž. 1998 31±40 View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Elsevier - Publisher Connector Comparison of the interaction of doxorubicin, daunorubicin, idarubicin and idarubicinol with large unilamellar vesicles Circular dichroism study Laurence Gallois, Marina Fiallo, Arlette Garnier-Suillerot ) Laboratoire de Physicochimie BiomoleculaireÂÂ et Cellulaire() URA CNRS 2056 , UniÕersite Paris Nord, 74, rue Marcel Cachin, 93017 Bobigny Cedex, France Received 6 August 1997; revised 25 September 1997; accepted 2 October 1997 Abstract Doxorubicin, daunorubicin and other anthracycline antibiotics constitute one of the most important groups of drugs used today in cancer chemotherapy. The details of the drug interactions with membranes are of particular importance in the understanding of their kinetics of passive diffusion through the membrane which is itself basic in the context of multidrug resistanceŽ. MDR of cancer cells. Anthracyclines are amphiphilic molecules possessing dihydroxyanthraquinone ring system which is neutral under the physiological conditions. Their lipophilicity depends on the substituents. The amino sugar moiety bears the positive electrostatic charge localised at the protonated amino nitrogen. The four anthracyclines used in this study doxorubicin, daunorubicin, idarubicin and idarubicinolŽ. an idarubicin metabolite readily formed inside the cells have the same amino sugar moiety, daunosamine, with pKa of 8.4. Thus, all drugs studied will exhibit very similar electrostatic interactions with membranes, while the major differences in overall drug-membrane behaviour will result from their hydrophobic features. Circular dichroismŽ. CD spectroscopy was used to understand more precisely the conformational aspects of the drug±membrane systems. Large unilamellar vesiclesŽ. LUV consisting of phosphatidylcholine, phosphatidic acidŽ. -
Anticancer Drugs
Temobel capsules 20 mg, 100 mg, 250 mg Trade name: Temobel. International nonproprietary name: Temozolomide. Pharmaceutical form: capsules 20 mg, 100 mg and 250 mg. Composition: each capsule contains: Active ingredients: temozolomide. Excipients: stearic acid, tartaric acid, colloidal anhydrous silica, sodium starch glycolate type A, anhydrous lactose. ATC code: L01AX03. Indications for use ▶ Children over the age of 3 years and adult patients ▶ Adult patients with newly-diagnosed glioblastoma with malignant glioma, such as glioblastoma multiforme concomitantly with radiotherapy and multiforme or anaplastic astrocytoma, showing subsequently as monotherapy. recurrence or progression aſt er standard therapy. Alkylating agents AmoxicillinTemodex powder for preparing capsules gel for local 250 usemg 100 mg Trade name: Temodex. Pharmacotherapeutic group: Antitumor agent of International non-proprietary name: Temozolomide. alkylating action. Description: powder from white to greenish-gray or ATC code: L01AX03. brown. Indications for use Composition: each package contains: temozolomide The newly discovered multiform glioblastoma (as part of (in the form of temodex (mixture of temozolomide and sodium dextran phosphate)) – 100 mg. combined treatment in combination with radiotherapy); Dosage form: powder for gel preparation for topical Malignant glioma (glioblastoma multiforme or anaplastic use. astrocytoma). retinoblastoma, lymphogranulomatosis, lymphosarcoma, Cyclophosphan non-Hodgkin lymphoma, reticulosarcoma, osteogenous sarcoma, multiple myeloma, -
Characterization of the Small Molecule Kinase Inhibitor SU11248 (Sunitinib/ SUTENT in Vitro and in Vivo
TECHNISCHE UNIVERSITÄT MÜNCHEN Lehrstuhl für Genetik Characterization of the Small Molecule Kinase Inhibitor SU11248 (Sunitinib/ SUTENT in vitro and in vivo - Towards Response Prediction in Cancer Therapy with Kinase Inhibitors Michaela Bairlein Vollständiger Abdruck der von der Fakultät Wissenschaftszentrum Weihenstephan für Ernährung, Landnutzung und Umwelt der Technischen Universität München zur Erlangung des akademischen Grades eines Doktors der Naturwissenschaften genehmigten Dissertation. Vorsitzender: Univ. -Prof. Dr. K. Schneitz Prüfer der Dissertation: 1. Univ.-Prof. Dr. A. Gierl 2. Hon.-Prof. Dr. h.c. A. Ullrich (Eberhard-Karls-Universität Tübingen) 3. Univ.-Prof. A. Schnieke, Ph.D. Die Dissertation wurde am 07.01.2010 bei der Technischen Universität München eingereicht und durch die Fakultät Wissenschaftszentrum Weihenstephan für Ernährung, Landnutzung und Umwelt am 19.04.2010 angenommen. FOR MY PARENTS 1 Contents 2 Summary ................................................................................................................................................................... 5 3 Zusammenfassung .................................................................................................................................................... 6 4 Introduction .............................................................................................................................................................. 8 4.1 Cancer .............................................................................................................................................................. -
Benefit of Intermediate-Dose Cytarabine-Containing Induction In
Letters to the Editor ter RFS and EFS rates and showed a marked tendency to Benefit of intermediate-dose cytarabine-containing improve the OS of patients with CEBPAdm in both uni- induction in molecular subgroups of acute myeloid variate and multivariable analyses, as shown in Online leukemia Supplementary Table S2. Five-year RFS, EFS, and OS rates were 85%, 81%, and 88% in the intermediate-dose com- The outcome of acute myeloid leukemia (AML) is pared with 56%, 56%, and 68% in the conventional- affected by disease characteristics as well as treatment dose group, respectively (Figure 1). In total, 13 of 75 1-3 regimens. In the CALGB8525 trial, patients with core (17%) patients with CEBPAdm AML underwent allo- binding factor (CBF)-positive leukemia benefited from geneic transplantation in CR1, including five of 32 (16%) 4 consolidation with a high dose of cytarabine. More in the conventional-dose group and eight of 43 (19%) in 2 recently, high-dose daunorubicin (60-90 mg/m ) has the intermediate-dose group. To analyze results in the 5,6 become widely used. High-dose daunorubicin confers a absence of any possible contributory effect of transplan- favorable prognosis for patients with NPM1 muta- tation, patients were censored at the time of transplanta- 1,7,8 tions. tion in CR1. Patients with CEBPAdm AML exposed to Higher-dose cytarabine was also introduced into AML intermediate-dose cytarabine achieved an increase in 5- 3,9 induction therapy. Recently, we investigated the role of year RFS, censored at the date of transplantation, from intermediate-dose cytarabine in induction therapy of 56% to 83% (hazard ratio [HR], 0.313; 95% confidence AML and found that the introduction of intermediate- interval [95% CI]: 0.119-0.824; Wald P=0.019) (Online dose cytarabine, combined with daunorubicin and omac- Supplementary Figure S3). -
Multifunctional Colloidal-Based Nanoparticles for Cancer Treatment Bioengineering and Nanosystems
Multifunctional colloidal-based nanoparticles for cancer treatment Rita Falcão Baptista Ribeiro Mendes Thesis to obtain the Master of Science Degree in Bioengineering and Nanosystems Supervisors: Doctor Marlene Susana Dionísio Lúcio Doctor Susana Isabel Pinheiro Cardoso de Freitas Examination Committee Chairperson: Doctor Gabriel António Amaro Monteiro Supervisor: Doctor Marlene Susana Dionísio Lúcio Members of the Committee: Doctor Maria Elisabete Cunha Dias Real Oliveira May 2017 Acknowledgments First of all I would like to thank to the college institutions where I fortunately had the opportunity to learn, grow and enrich myself during all my academic life, Instituto Superior Técnico (IST) and Universidade do Minho (UM). I would like to thank to Doctor Maria Elisabete Cunha Dias Real Oliveira the opportunity that gave me by accepting my request of working in the UM research team from the very first moment and all the concern and human support along the entire year. The present work would not be possible without all the availability, kindness and care that was always given to me during all the period of works. Secondly, I have to write a special word to my supervisor Doctor Marlene Susana Dionísio Lúcio, which despite the amount of work within hands, always had a time to support me and teach me with the major patience and commitment. The contagious passion for the scientific world that was constantly present in every single explanation was one of the most crucial aspects for the success of this work and for making me grow as a scientist and as a human being. I would always have to thank all the incredible technical and human support that was given to me all the time.