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Liposomal daunorubicin
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Daunorubicin inhibits dna and rna synthesis by intercalation between dna base pairs and by steric obstruction; and intercalates at points of local uncoiling of the double helix. PHARMACEUTICAL APPENDIX TO THE TARIFF SCHEDULE 12 Table 1 con. ; Product CAS Number CYCLEXANONE CYCLIRAMINE CYCLIZINE CYCLOBARBITAL CYCLOBENZAPRINE CYCLOBUTOIC ACID CYCLOBUTYROL CYCLOFENIL CYCLOGUANIL EMBONATE CYCLOMENOL CYCLOMETHYCAINE CYCLOPENTAMINE CYCLOPENTHIAZIDE CYCLOPENTOLATE CYCLOPHOSPHAMIDE CYCLOPREGNOL CYCLOPROPANE CYCLOPYRRONIUM BROMIDE CYCLOSERINE CYCLOTHIAZIDE CYCLOVALONE CYCOTIAMINE CYCRIMINE CYHEPTAMIDE CYHEPTROPINE CYNARINE CYPENAMINE CYPRAZEPAM CYPRENORPHINE CYPRODENATE CYPROHEPTADINE CYPROLIDOL CYPROTERONE CYROMAZINE CYSTEINE CYTARABINE DACARBAZINE DACEMAZINE DACISTEINE DACLIXIMAB DACOPAFANT DACTINOMYCIN DACURONIUM BROMIDE DAGAPAMIL DALANATED INSULIN DALBRAMINOL DALEDALIN DALFOPRISTIN DALTEPARIN SODIUM DALTROBAN DALVASTATIN DAMETRALAST DAMOTEPINE DANAZOL DANIQUIDONE DANITRACEN DANOFLOXACIN DANOSTEINE DANTROLENE DANTRON DAPABUTAN DAPIPRAZOLE DAPOXETINE DAPSONE DAPTOMYCIN DARENZEPINE DARGLITAZONE DARIFENACIN DARODIPINE DARSIDOMINE DATELLIPTIUM CHLORIDE DAUNORUBICIN DAZADROL DAZEPINIL DAZIDAMINE DAZMEGREL DAZOLICINE DAZOPRIDE DAZOQUINAST DAZOXIBEN DEANOL ACEGLUMATE DEBOXAMET DEBRISOQUINE DEBROPOL DECAMETHONIUM BROMIDE DECIMEMIDE Product 15301-52-7 47128-12-1 82-92-8 DECITABINE DECITROPINE DECLENPERONE DECLOXIZINE DECOMINOL DECOQUINATE DECTAFLUR DEDITONIUM BROMIDE DEFERIPRONE DEFEROXAMINE DEFIBROTIDE DEFLAZACORT DEFOSFAMIDE DEHYDROCHOLIC ACID DEHYDROEMETINE DELANTERONE DELAPRIL DELAVIRDINE DELEQUAMINE DELERGOTRILE DELFANTRINE DELFAPRAZINE DELMADINONE DELMETACIN DELMOPINOL DELORAZEPAM DELOXOLONE DELPROSTENATE DEMBREXINE DEMECARIUM BROMIDE DEMECLOCYCLINE DEMECOLCINE DEMECYCLINE DEMEGESTONE DEMELVERINE DEMEXIPTILINE DEMOCONAZOLE DEMOXEPAM DEMOXYTOCIN DENATONIUM BENZOATE DENAVERINE DENBUFYLLINE DENIPRIDE DENOPAMINE DENOTIVIR DENPIDAZONE DENZIMOL DEPRAMINE DEPRODONE DEPROSTIL DEPTROPINE DEQUALINIUM CHLORIDE DERAMCICLANE DERIGLIDOLE DERPANICATE DESASPIDIN DESCICLOVIR DESCINOLONE DESERPIDINE DESFLURANE DESGLUGASTRIN DESIPRAMINE DESIRUDIN DESLANOSIDE DESLORELIN DESMETHYLMORAMIDE DESMOPRESSIN DESOCRIPTINE DESOGESTREL DESOMORPHINE DESONIDE DESOXIMETASONE DESOXYCORTONE DETAJMIUM BITARTRATE DETANOSAL DETERENOL DETIRELIX DETOMIDINE DETORUBICIN DETRALFATE DETROTHYRONINE DETUMOMAB DEVAPAMIL DEVAZEPIDE DEXAMETHASONE DEXAMETHASONE ACEFURATE CAS Number 2353-33-5 1242-69-9 63388-37-4 A total of 96 combinations of an antineoplastic antibiotic with an antibacterial drug were tested on each of the 28 strains by the cellophane transfer technique, i.e., 448 combinations for each antineoplastic antibiotic, a total of 2, 688 combinations. Generally, synergism and antagonism were infrequent 5.8 and 7.1%, respectively ; , most of the combinations showing indifference. Synergism and antagonism were rare with dactinomycin 1.1 and 1.6% of the combinations, respectively ; and with mithramycin 1.1 and 2.0% respectively ; . The combination of dactinomycin with chloramphenicol was synergistic on one strain of P. rettgeri, for which dactinomycin was bactericidal, and one strain of P. mirabilis, against which it showed no activity. The combination of dactinomycin with tetracycline was synergistic on one strain of E. coli. Synergism and antagonism were seen slightly more frequently in combinations of daunorubicin 4.9 and 3.3% ; and of doxorubicin 3.3 and 4.2%, respectively ; . With daunorubicin, antagonism was seen with gentamicin on three strains, with kanamycin on two strains, and with streptomycin on one strain of K. pneumoniae. Doxorubicin produced antagonism with gentamicin and with kanamycin on three strains and with streptomycin on one strain of K. pneumoniae. Table 1 shows the detailed results of the cellophane transfer technique with combinations of mitomycin C. Eighty-eight combinations 19.6% ; demonstrated synergism, whereas 31 combinations 6.9% ; were antagonistic. Synergism was frequently seen with carbenicillin but not with the other 8i-lactam antibiotics ; on strains of E. coli and P. aeruginosa, and also with the aminoglycosides, with chloramphenicol on E. coli and Proteus spp. ; and with nalidixic acid except on P. aeruginosa ; . Bleomycin was antagonistic in 112 combinations 25% ; , and it was rarely synergistic 4.2% ; . Table 2 summarizes the results of combinations of the antibacterial drugs with bleomycin and shows the synergism and antagonism found on strains of E. coli and K. pneumoniae. These combinations almost always showed indifference on Proteus and on P. aeruginosa and details are therefore not shown. On E. coli and K. pneumoniae bleomycin generally showed antagonism when combined with the 8-lactam antibiotics, the aminoglycosides, rifampin, erythromycin and clindamycin, chloramphenicol and tetracycline, and colistin. It did however show synergism with nalidixic acid on some strains of E. coli but antagonism on K. pneumoniae. Occasionally, both synergism and antagonism were seen in the same combination; these phenomena were concentration dependent. Table 3 shows. Daunorubicin for amlFig. 3. Ability of sugar-modified anthracycline derivatives to block exonuclease. A, structure of idarubicin and sugar-modified anthracyclines. In B, the 296-bp DNA fragment was isolated from cells treated with a combination of 500 M AN-9 and either 4 M Adriamycin Ad ; , idarubicin Id ; , 4-demethoxy 3 -deamino 4 -deoxy 4 -epi amino daunorubicin 1 ; , 4demethoxy 3 -deamino 3 -hydroxy 4 -epi doxorubicin 2 ; , or Adriamycinone 3 ; . Control samples C ; that were untreated are also shown. Samples were either analyzed directly exo ; or exposed to exonuclease digestion exo ; . The same exonuclease blockage sites for all drugs were observed in two independent experiments. 1. Decter M. Healing Medicare: Managing Health System Change the Canadian Way. Toronto: McGilligan Books, 1994. 2. Leatt P, Baker GR, Halverson PK, Aird C. Downsizing, reengineering, and restructuring: long-term implications for healthcare organizations. Front Health Serv Manage 1997; 13: 337. Brannon RL. Restructuring hospital nursing: reversing the trend toward a professional work force. Int J Health Serv 1996; 26: 643654. Walston SL, Burns LR, Kimberly JR. Does reengineering really work? An examination of the context and outcomes of hospital reengineering initiatives. Health Serv Res 2000; 34: 13631387. Burke RJ, Greenglass ER. Hospital restructuring and downsizing in Canada: are less experienced nurses at risk? Psychol Rep 2000; 87: 10131021. Donelan K, Blendon RJ, Schoen C, Davis K, Binns K. The cost of health system change: public discontent in five nations. Health Aff 1999; 18: 206216. Donelan K, Blendon RJ, Schoen C, Binns K, Osborn R, Davis K. The elderly in five nations: the importance of universal coverage. Health Aff 2000; 19: 226235. Blendon RJ, Schoen C, Donelan K et al. Physicians' views on quality of care: a five-country comparison. Health Aff 2001; 6: 233243. Aiken LH, Clarke SP, Sloane DM. Hospital restructuring: does it adversely affect care and outcomes? J Nurs Admin 2000; 30: 457465. Davidson H, Folcarelli P, Crawford S et al. The effects of health care reform on job satisfaction and voluntary turnover among hospital-based nurses. Med Care 1997; 35: 634645. Buerhaus PI, Staiger DO. Trouble in the nurse labor market? Recent trends and future outlook. Health Aff 1999; 18: 214222. Berens MJ. Nursing mistakes kill, injure thousands. Chicago Tribune, September 10, 2000. 13. Driedger SD. The nurses: the front-line caregivers are burned out. Is it any wonder? Macleans 1997; 110: 2427. Kendall P. One nurse in three `is ready to resign'. Daily Mail London ; , May 7, 2001; 15. Trafford A. When the hospital staff isn't enough. Washington Post, January 7, 2001; A1 & A4. 16. Aiken LH, Sochalski JA eds ; . Hospital restructuring in North America and Europe: patient outcomes and workforce implications. Med Care 1997; 35 Suppl.: 152. 17. Sochalski JA, Aiken LH. Accounting for variation in hospital outcomes: a cross-national study. Health Aff 1999; 18: 256259. Aiken LH, Sochalski JA, Lake ET. Studying outcomes of and deferasirox. Daunorubicin patentDaunorubicin wikipediaTime is a vital factor when an order is placed for hospital equipment and supplies. Often a single day's delay can aggravate or create a crisis! And having to order from different sources can make purchasing complicated. The ideal is a single reliable source for quality hospital equipmentand supplies--Liquid Carbon ic. Medical gases, regulators, flowmeters, anaest hetic machines, masks, respirators . and even complete central piping systems are available at a moment's notice from at y one of our nationa l network of branches and plants. When quality and service are the determ ining factors, look to LIQUID CARBONIC--exclusiv e Canadian distributors of world-famous AGA and MIVAB hospital equipment from Sweden. Daunorubicin citrateSpecificity. Molecular Immunology 42: 1111-9, 2005. McLean GR, Olsen OA, Watt IN, Rathanaswami P, Leslie KB, Babcook JS & Schrader JW. Recognition of HCMV by human primary immunoglobins identifies as innate foundation to an adaptive immune response. J Immunology 174: 4768-78, 2005. Wang B, David M, and Schrader JW. Absence of Caprin-1 results in defects in cellular proliferation. J Immunol 175: 4274-81, 2005. David M, Cochrane CL, Duncan SK, and Schrader JW. Pure lipopolysaccharide or synthetic Lipid A induces activation of p21Ras in primary macrophages through a pathway dependent on Src family kinases and PI3K. J Immunol 175: 8236-41, 2005. Shepherd, Dr. John D Lavoie JC, Connors JM, Phillip G, Reece D, Barnett MJ, Forrest D, Gascoyne R, Hogge D, Nantel SN, Shepherd JD, Smith C, Song KW, Sutherland H., Toze C, Voss NJ and Nevill T. High-dose chemotherapy and autologous stem cell transplantation for primary refractory or relapsed Hodgkin lymphoma: long-term outcome in the first 100 patients treated in Vancouver. Blood 106: 1473-1478, 2005. Song KW, Mollee PN, Hogge DE, Gupta V, Barnett MJ, Forrest DL, Lavoie JC, Nevill TJ, Nantel SH, Shepherd JD, Smith CA, Sutherland HJ, Toze CL, Crump M & Keating A. Predictive value of karyotype on outcome of autotranplants for Acute Myeloid Leukemia in second remission. Leuk Lymphoma 46: 525-531, 2005. Forrest DL, Hogge DE, Nevill TJ, Nantel SH, Barnett MJ, Shepherd JD, Sutherland HJ, Toze CL, Smith CA, Lavoie JC, Song KW, Voss NJ, Gascoyne RD, Connors JM. High-dose therapy and autologous hematopoietic stem cell transplantation does not increase risk of second neoplasms for patients with Hodgkin's Lymphoma: A comparison of conventional therapy alone versus conventional therapy followed by autologous hematopoietic stem cell transplantation. J Clin Oncol 23: 7994-8002, 2005. Doocey RT, Toze CL, Connors JM, Nevill TJ, Gascoyne RD, Barnett MJ, Forrest DL, Hogge DE, Lavoie JC, Nantel SH, Shepherd JD, Sutherland HJ, Voss NJ, Smith CA, Song KW. Allogeneic haematopoietic stem-cell transplantation for relapsed and refractory aggressive histology non-Hodgkin lymphoma. Br J Haematol 131: 223-230, 2005. Toze CL, Galal A, Barnett MJ, Shepherd JD, Conneally EA, Hogge DE, Nantel SH, Nevill TJ, Sutherland HJ, Connors JM, Voss NJ, Kiss TL, Messner HA, Lavoie JC, Forrest DL, Song KW, Smith CA, Lipton J. Myeloablative allografting for chronic lymphocytic leukemia: evidence for a potent graft-versus-host effect associated with graft-versus-host disease. Bone Marrow Transplant 36: 825-830, 2005. van der Holt B, Lowenberg B, Burnett AK, Knauf WU, Shepherd J, Piccaluga PP, Ossenkoppele GJ, Verhoef GE, Ferrant A, Crump M, Selleslag D, Theobald M, Fey MF, Vellenga E, Dugan M, Sonneveld P. The value of the MDR1 reversal agent PSC-833 in addition to daunorubicin and cytarabine in the treatment of elderly patients with previously untreated acute myeloid leukemia AML ; , in relation to MDR1 status at diagnosis. Blood 106: 2646-2654, 2005. Smith, Dr. Clayton A Forrest DL, Hogge DE, Nevill TJ, Nantel SH, Barnett MJ, Shepherd JD, Sutherland HJ, Toze CL, Smith CA, Lavoie JC, Song KW, Voss NJ, Gascoyne RD, Connors JM. High-dose therapy and autologous hematopoietic stem cell transplantation does not increase risk of second neoplasms for patients with Hodgkin's Lymphoma: A comparison of conventional therapy alone versus conventional therapy followed by autologous hematopoietic stem cell transplantation. J Clin Oncol 23: 7994-8002, 2005. Lavoie JC, Connors JM, Phillips GL, Reece DE, Barnett MJ, Forrest DL, Gascoyne RD, Hogge DE, Nantel SH, Shepherd JD, Smith CA, Song KW, Sutherland HJ, Toze CL, Voss NJS, Nevill TJ. Daunorubicin sourceJensen et al. Bristol-Myers Squibb Co., Lyngby, Denmark ; , teniposide BristolMyers Squibb Co. ; , and mitoxantrone Lederle, Glostrup, Denmark ; were in solution for infusion. Maleimide, NMM, and NEM were dissolved in water just before use, due to rapid hydrolysis. Cells. The classical human SCLC cell line NCI-H69 is described in Carney et al., 1985 ; . The two derivatives of this cell line, NCI-H69 DAU and NCI-H69 VP, have been developed in our laboratory by selection to gradually increasing concentrations of daunorubicin and etoposide, respectively, as described previously Jensen et al., 1989, 1993b ; . The variant human SCLC cell line OC-NYH is described in de Leij et al. 1985 ; . The murine cell lines EHR2 and L1210 have been described in Friche et al. 1991 ; and Jensen et al. 1993a ; , respectively. Preparation of 3H-Labeled Kinetoplast DNA kDNA ; . Tritium-labeled kDNA was isolated from Crithidia fasciculata as described in Sahai and Kaplan 1986 ; . Purification of Human Topoisomerase II . The purification of wt and mutant human topoisomerase II from overexpressing yeast cells was carried out as described in Wessel et al. 1999 ; . Determination of Topoisomerase II Catalytic Activity. Topoisomerase II catalytic activity was measured by kDNA decatenation assay. 3H-Labeled kDNA 200 ng ; isolated from C. fasciculata was incubated with increasing concentrations of drug in 20 l reaction buffer containing 10 mM Tris-HCl pH 7.9, 50 mM NaCl, 50 mM KCl, 5 mM MgCl2, 1 mM EDTA, 15 g ml BSA, and 1 mM Na2ATP all from Sigma-Aldrich ; with 1 U of purified wt or mutant topoisomerase II for 20 min at 37C. One unit of activity was defined as the amount of enzyme required for complete decatenation in the absence of drug. After addition of stop buffer containing 5% Sarkosyl, 0.0025% bromphenol blue, and 25% glycerol all from Sigma-Aldrich ; , unprocessed kDNA network, and decatenated DNA circles were separated by filtering, and the amount of unprocessed kDNA in each reaction was determined by scintillation counting Packard BioScience, Meriden, CT ; . Plasmid Cleavage Assay. A modification of the protocol described in Burden et al. 2001 ; was used. Purified human topoisomerase II 350 ng ; , 400 ng of pUC18 DNA, and increasing concentrations of drugs were incubated for 6 min at 37C in 20 l topoisomerase II cleavage buffer 10 mM Tris-HCl pH 7.9, 50 mM NaCl, 50 mM KCl, 5 mM CaCl2, 1 mM EDTA, 15 g ml BSA, and 1 mM Na2ATP; all from Sigma-Aldrich ; . Next, the cleavable complex was trapped by adding 2 l of 10% SDS. After vigorous vortexing 1.5 l of 0.25 M EDTA and 2 l of proteinase K 0.8 g ml ; in proteinase buffer 50 mM Tris-HCl pH 7.9 and 1 mM CaCl2 ; was added and the samples vortexed. After a 30-min incubation at 45C, 5 l of loading buffer 5% Sarkosyl, 0.0025% bromphenol blue, and 25% glycerol ; was added and the samples were exposed to 70C for 5 min. Next, samples were run through a 0.8% agarose gel in 1 Tris acetate EDTA buffer for 3 h at separate different topological forms of plasmid DNA. Finally the gels were stained in distilled water containing 10 g ml ethidium bromide for 15 min followed by destaining in distilled water for 1 h before they were photographed in UV light. Clonogenic Assay. A 3-week clonogenic assay using soft agar on a sheep red blood cell feeder layer was used as described in Jensen et al. 1993b ; . For the study of maleimide-mediated antagonism of topoisomerase II poison-induced cytotoxicity cells were incubated with the appropriate drugs for a fixed time, washed twice, and then plated in agar in the absence of drugs. For the study of cytotoxicity itself continuous drug exposure was used. Alkaline Elution. For the determination of drug-induced DNA damage in vivo the alkaline elution assay Kohn et al., 1976 ; was used with modifications as described in Sehested et al. 1998 ; . Depletion of Cellular ATP. Cellular ATP depletion was obtained by incubating cells with azide and 2-deoxyglucose both from Sigma-Aldrich ; as described in Sorensen et al. 1999 ; . Band Depletion Assay. Band depletion assay was performed as described in Sehested et al. 1998 ; by using the enhanced chemilu. Daunorubicin molecular weightDemonstrated Progress for BIVN; What to Expect for 2005 2006 Aug `03: Bioenvision secures Modrenal marketing rights in the U.K. May `04: Bioenvision extends exclusive right to market Clofarabine in Southeast Asia and Japan Jul `04: Bioenvision files for Clofarabine approval in Europe Dec `05: Clofarabine approved by the FDA for treatment of pediatric ALL patients Jun `05: Clofarabine reviewed favorably at a European Hematology Association meeting in Sweden Q2 FY'06: Interim results on Virostat's Phase II Hepatitis reported Dec `05 Q2 FY'06 ; : Phase II adult AML study completed patient enrollment and reported preliminary results Dec `05 Q2 FY'06 ; : Phase II multi-center pediatric ALL reported preliminary results; patient enrollment is ongoing 1H FY'06: Initiation of NCRI MRC ; Phase III clofarabine + daunorubicin ; in refractory relapsed adult AML Jan `06: Additional data requested by EMEA to be submitted Mar `06: EMEA decision on pediatric ALL expected 2H FY'06: Initiation of Phase II Velostan study in bladder cancer 2H FY'06: Initiation of Confirmatory Phase II trials clofarabine + Ara-C, clofarabine + cyclophosphamide ; in the US Griffin Securities, Inc., 17 State Street, New York, NY, 10004 Member NASD, SIPC 212 ; 509-9500 and dextroamphetamine. Daunorubicin msds
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