Daunorubicin topoisomerase

This work was supported by Grant CA 28896 and Cancer Center Support Grant CA 30199 from the National Cancer Institute, National Institutes of Health, Department of Health and Human Services. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. 3 Recipient of a National Research Service Award fellowship from the National Cancer Institute, National Institutesof Health, Department of Health and Human Services. 30. List AF, Spier CC, Abbaszadegan M, Grogan TM, Greer JP, Wolf SN, Scheper RJ, Dalton WS: Non-P-glycoprotein PGP ; mediated multidrug resistance MDR ; : Identification of a noveldrug resistance phenotype with prognostic relevance in acute myeloid leukemia AML ; . Blood 82: 443a, 1993 abstr ; 31. Holmes JA, Whittaker JA, Padua R Effect of position 185 mutations of the MDRl gene on drug resistance in leukemia. Leukemia 6: 484, 1992 Miyamoto K, Inoko K, Wakusawa S , Kajita S, Hasegawa T, Takagi K, Koyama M: Inhibition of multidrug resistance by a new staurosporine derivative, NA-382, in vitro and in vivo. Cancer Res 53: 1555, 1993 Wakusawa S , Inoko K, Miyamoto K Staurosporine derivatives reverse multidrug resistance without correlation with their protein kinase inhibitory activity. J Antibiot 46: 353, 1993 Ma L, Marquardt D, Takemoto L, Center M: Analysis of P-gp phosphorylation in HL60 cells isolated for resistance to vincristine. J Biol Chem 266: 5593, 1991 Gollapudi S , Pate1 K, Gupta S : Protein kinase C isoforms in multidrug resistant P388 ADR cells: a possible role in daunorubicin et transport. Cancer L t 62: 69, 1992 Blobe G, Sachs C, Khan W, Fabbro D, Stabel S , Wetsel W, Obeid L, Fine R, Hannun Y: Selective regulation of expression of protein kinase C PKC ; isoenzymes in multidrug-resistant MCF-7 cells: Functional significance of enhanced expression of PKC a. J Biol Chem 268: 658, 1993 Komada F, Nishikawa M, Uemura Y, Morita K, Hidaka H, Shirakawa S: Expression of three major protein kinase C isoenzymes in various types of human leukemic cells. Cancer Res 51: 4271, 1991 Herbert JM, Augereau JM, Gleye J, Maffrand J P Chelerythrine is a potent and specific inhibitor of protein kinase C. Biochem Biophys Res Commun 172: 993, 1990.

2, 3, 4, no significant difference between daunorubicin and mitoxantrone has been reported. To the Editor: Anaesthetists have felt secure in reusing syringes from patient to patient as long as needles were changed and the solution had not obviously been contaminated with blood. Over the last decade, this practice has become less common. Many feel that injecting a drug, at the port most distant from the patient in an intravenous line will guarantee the syringe contents to be free of contamination. However, the contamination rate with blood is between 3.3% and 0.3% depending on the distance of the port from the catheter.1 The presence of the one way valve in the administration set will in most instances prevent back flow of blood from the patient to the most distant port. However, the competence of the one way valve cannot be guaranteed, as demonstrated by Crosby while injecting propofol.2 Only minimal contamination with blood to transmit viral disease.1 The contents of a refilled syringe cannot be guaranteed to be free of contamination.3 Health Canada in August 1994 stated that the practice of using single use low osmolar dye intravenous delivery systems on more than one patient is potentially unsafe.41 suggest that the reuse of syringes in anaesthesia is analogous and should be subject to this advisory notice. There is a small but finite risk of nosocomial infection from reuse of syringes and infusions. It is difficult, if not impossible, to trace an infection with a long latent period i.e., hepatitis B, hepatitis C, HIV ; to an anesthetic some weeks or months previously. Cost containment and convenience do not justify reuse of syringes. Gary B. Skidmore MD FRCPC Department of Anaesthesia, Faculty of Medicine University of Ottawa 501 Smyth Ottawa, Ontario K1H 8L6.

Gestational diabetes on insulin Emergency cesarean section Fetal distress Meconium stained liquor in early labor Failure to progress Cesarean section rate 10 32 31.2% ; 9 and deferasirox. Materials--The anti-dGK antibodies were prepared as described 13 ; . Anti-cytochrome c antibodies were obtained from CLONTECH. An anti-adenine nucleotide translocase ANT ; antibody preparation was a gift from Dr. Patrik Andree, Clinical Research Center, Div. of Medical Cell Biology, Karolinska Institute, NOVUM, Huddinge, Sweden. Cell Culture and Treatments--Human epithelial kidney HEK ; 293 cells were cultivated in Dulbecco's Modified Eagle Medium with GLUTAMAX ITM supplemented with 10% v v ; fetal calf serum, 1 mM sodium pyruvate, and 1% v v ; antibiotic antimycotic solution Life Technologies, Inc. ; . Human lymphoblast Molt-4 cells were grown in RPMI 1640 medium supplemented with 10% v v ; heat-inactivated fetal calf serum and 1% v v ; antibiotic antimycotic solution Life Technologies, Inc. ; . Cells grown to late log-phase were treated with daunorubicin Rhone-Poulenc Rorer, Bristol, England ; 110 M for 6 h ; or CdCl2 20.
Menlo Park, Cal., and obtained through Dr. J. A. R. Mead of the National Institutes of Health. ACKNOWLEDGMENT This work was supported in part by USPHS Grant GM 10548. REFERENCES and delavirdine.
Anthracyclines-induced cardiotoxicity, including a calcium overload [5], free radical production [6] or on-free radical" theory [3, 4]. Anthracyclines inhibit the uptake of calcium by the sarcoplasmatic reticulum preventing the myofibrilar apparatus from relaxing and according to some data, contributing to the myocardial dysfunction, initially subclinical and possibly becoming clinical heart failure subsequently [7]. Treatment with anthracyclines can be associated with different types of cardiotoxicity, including acute toxicity, subacute toxicity, chronic toxicity and delayed toxicity [4]. Treatment with daunorubicin is safe as long as a cumulative dose of 500 550 mg m2 is not exceeded [1, 8]. With increased cumulative dose, the risk of cardiotoxicity is increased. At a cumulative dose of less than 400 mg m2 the risk of chronic heart failure is 0.14 %, while at 550 mg m2 this risk becomes 7 % and increases to 18.0 % with 700 mg m2 [9]. A major obstacle to the therapeutic use of anthracyclines is the fact that their administration results in dose-dependent cardiomyopathy. Schwartz et al. showed that inter-individual variability exists in serious adverse effects. In his study 17 % of pacient had cardiotoxicity, but their dosis of anthracycline was in interval 75 1095 mg m2. On the other hand, 50 % of pacient had no cardiotoxicity and their cumulative dose was 1000 mg m2 [10]. Another risk factor identified was the schedule of administration of the drug since a decrease in cardiac toxicity was correlated with a decreased plasma peak concentration of the drug. This is apparently the critical factor for the toxicity [5]. The acute and subacute toxicities, as the name implies, can happen right after the administration of an anthracycline and is not dose-dependent. It consists of non-specific EKG changes in ST and T wave, QRS, QT interval [9], and is characterized by tachycardia [11]. The standard for monitoring anthracycline cardiotoxicity is the direct microscopic visualisation of cardiac tissue biopsy [12]. A grading system of the biopsy specimen has been devised, with the purpose of early detection of the toxicity and modification or discontinuation of the treatment. The histology findings in anthracyclines cardiomyopathy include hypertrophy, vacuolisation, myofibrillar loss, necrosis and eventually fibrosis, increasing gradually with increasing cumulative dose of anthracyclines [12]. Previous studies show that anthracyclines induce cardiotoxicity in rabbits given 3 mg kg per week for 10 weeks. Cardiac left ventricular contractility was significantly decreased in treated animals assayed at 5 7 day after the last administration [13]. In normotensive rats daunorubicin at 2.5 mg kg three times per week during one month was found to be lethal and all animals were sacrified after 8 weeks after final dose [14]. Here we report that daunorubicin cardiotoxicity is not dependent only on the cumulative dose, but is dependent on the schedule of administration as well.

Kits for doing so have been marketed. In this study we evaluated the clinical usefulness of determinations of the serum CK-B subunit. We used the Boehringer immunoinhibition kit in the diagnosis of chest pain and compared its diagnostic effectiveness with that of measuring total serum CK.

Porverful fungi enhances respirationand circulation, increasing staminaand resistance disease. to \iThile thesetonic herbscan be usedassingles, is evenmore it beneficialto take them in combination. A formula providesthe benefitsofseveraltonic herbsin one convenientdose.So hereare some tonic herbal formulas that can help ro counteractsome of the factorsthat causeus to grow weakeraswe age and desipramine. 45. Kottaridis PD, Gale RE, Frew ME, et al. The presence of a FLT3 internal tandem duplication in patients with acute myeloid leukemia AML ; adds important prognostic information to cytogenetic risk group and response to the first cycle of chemotherapy: analysis of 854 patients from the United Kingdom Medical Research Council AML 10 and 12 trials. Blood. 2001; 98: 1752-1759. Leith CP, Kopecky KJ, Godwin J, et al. Acute myeloid leukemia in the elderly: assessment of multidrug resistance MDR1 ; and cytogenetics distinguishes biologic subgroups with remarkably distinct responses to standard chemotherapy: a Southwest Oncology Group study. Blood. 1997; 89: 33233329. Leith CP, Kopecky KJ, Chen IM, et al. Frequency and clinical significance of the expression of the multidrug resistance proteins MDR1 P-glycoprotein, MRP1, and LRP in acute myeloid leukemia: a Southwest Oncology Group study. Blood. 1999; 94: 1086-1099. Baldus CD, Tanner SM, Ruppert AS, et al. BAALC expression predicts clinical outcome of de novo acute myeloid leukemia patients with normal cytogenetics: a Cancer and Leukemia Group B study. Blood. 2003; 102: 16131618. Huyghe P, Coiteux V, Sagot C, et al. Mutations of CEBPA, FLT3 and RAS in patients with de novo adult leukemia: a study from the Acute Leukemia French Association ALFA ; [abstract]. Blood. 2003; 102 pt 1 ; : 99a. Abstract 336. 50. Schnittger S, Thiede C, Kern W, et al. Partial tandem duplication of the MLL-gene MLL-PTD ; : a metaanlysis of 2885 AML patients enrolled into the German AMLCG99 and AML96 SHG trials [abstract]. Blood. 2003; 102 pt 1 ; : 100a. Abstract 340. 51. Frohling S, Schlenk RF, Kreitmeier S, et al. CEBPA mutations in younger adults with acute myeloid leukemia and normal cytogenetics: prognostic relevance and analysis of cooperating mutations [abstract]. Blood. 2003; 102 pt 1 ; : 99a. Abstract 337. 52. Falini B, Mecucci C, Tiacci E, et al, GIMEMA Acute Leukemia Working Party. Cytoplasmic nucleophosmin in acute myelogenous leukemia with a normal karyotype [published correction appears in N Engl J Med. 2005; 352: 740]. N Engl J Med. 2005; 352: 254-266. Berman E, Heller G, Santorsa J, et al. Results of a randomized trial comparing idarubicin and cytosine arabinoside with daunorubicin and cytosine arabinoside in adult patients with newly diagnosed acute myelogenous leukemia. Blood. 1991; 77: 1666-1674. Wiernik PH, Banks PL, Case DC Jr, et al. Cytarabine plus idarubicin or daunorubicin as induction and consolidation therapy for previously untreated adult patients with acute myeloid leukemia. Blood. 1992; 79: 313-319. Vogler WR, Velez-Garcia E, Weiner RS, et al. A phase III trial comparing idarubicin and daunorubicin in combination with cytarabine in acute myelogenous leukemia: a Southeastern Cancer Study Group study. J Clin Oncol. 1992; 10: 1103-1111. Wheatley K, AML Collaborative Group L. Meta-analysis of randomized trials of idarubicin IDAR ; or mitoxantrone MITO ; versus daunorubicin DNR ; as induction therapy for acute myeloid leukemia AML ; [abstract]. Blood. 1995; 86: 434a. Abstract 1724. 57. Rowe JM, Neuberg D, Friedenberg W, et al. A phase III study of daunorubicin vs idarubicin vs mitoxantrone for older adult patients 55 yrs ; with acute myelogenous leukemia AML ; : a study of the Eastren Cooperative Oncology Group E3993 ; [abstract]. Blood. 1998; 92 suppl 1, pt 1 ; : 313a. Abstract 1284. 58. Vignetti M, De Witte TM, Suciu S, et al. Daunorubicin DNR ; vs mitoxantrone MTZ ; vs idarubicin administered during induction and consolidation in acute myelogenous leukemia AML ; followed by autologous or allogeneic stem cell transplantation SCT ; : results of the EORTC-GIMEMA [abstract]. Blood. 2003; 102 pt 1 ; : 175a. Abstract 611. 59. Bishop JF, Lowenthal RM, Joshua D, et al, Australian Leukemia Study Group. Etoposide in acute nonlymphocytic leukemia. Blood. 1990; 75: 2732. Russo D, Malagola M, Martinelli G, et al. Efficacy and toxicity of FLAI vs ICE for induction treatment of newly diagnosed AML patients, younger than 60 years [abstract]. Blood. 2004; 104 pt 1 ; : 250a. Abstract 878. 61. Mayer RJ, Davis RB, Schiffer CA, et al, Cancer and Leukemia Group B. Intensive postremission chemotherapy in adults with acute myeloid leukemia. N Engl J Med. 1994; 331: 896-903.