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Increasing the accumulation of daunorubicin in human leukemic cells by prolonging the infusion time.Leukemia Research 1989Eight patients with acute nonlymphoblastic leukemia were treated with a combination of daunorubicin (1.5 mg/kg body weight) and cytosine arabinoside. The infusion time...
Eight patients with acute nonlymphoblastic leukemia were treated with a combination of daunorubicin (1.5 mg/kg body weight) and cytosine arabinoside. The infusion time of daunorubicin was varied from 10 min to 24 h. One patient received the drug during 24 h in one treatment course and during 10 min in the subsequent course. The concentrations of daunorubicin and its main metabolite, daunorubicinol, were monitored simultaneously in plasma and in leukemic cells using high performance liquid chromatography. Infusion during 24 h gave a peak plasma concentration of daunorubicin that was less than one tenth of that observed after infusion for 10 min, while the areas under the plasma concentration vs time curves were similar. In contrast, prolonging the infusion time increased the area under the cellular concentration vs time curve from a mean of 3.3 nmol x h/mg cell protein for infusions less than one hour to 13.7 and 17.0 nmol x h/mg cell protein in two patients who received the same dose as a 24-h infusion. The duration of the infusion did not influence the intracellular levels of daunorubicinol. We conclude that the infusion times appear to affect the concentration of daunorubicin in the leukemic cells and may be important for the therapeutic effects of daunorubicin.
Topics: Cell Transformation, Neoplastic; Daunorubicin; Humans; Infusions, Intravenous; Intracellular Fluid; Leukemia, Myeloid, Acute; Male; Middle Aged
PubMed: 2927175
DOI: 10.1016/0145-2126(89)90145-8 -
Medical Oncology and Tumor... 1987Levels of plasma daunorubicin, daunorubicinol and aglycone metabolites were measured in 47 patients 3 h after daunorubicin was administered daily for three days as part...
Levels of plasma daunorubicin, daunorubicinol and aglycone metabolites were measured in 47 patients 3 h after daunorubicin was administered daily for three days as part of a cytosine arabinoside/daunorubicin remission induction regimen. High-pressure liquid chromatography with fluorescence detection was used for separation and quantitation of the drug and its metabolites. A wide range of plasma levels were observed regardless of the outcome of therapy. Patients who had high levels of the drug, or daunorubicinol on day 1 of therapy tended to have high levels on days 2 and 3 of the regimen. Three hours after the third daily dose of daunorubicin was administered, patients who would not enter remission had significantly higher levels of aglycone metabolites in plasma than did patients who entered remission. These data indicate that resistance to chemotherapeutic effects of daunorubicin may be connected with metabolism of the drug, especially with enhanced metabolism to aglycones.
Topics: Acute Disease; Biotransformation; Daunorubicin; Humans; Injections, Intravenous; Kinetics; Leukemia; Naphthacenes
PubMed: 3600054
DOI: 10.1007/BF02934931 -
Nuclear Medicine and Biology Aug 2006Auger electron emitters, such as (125)I, are getting increasingly wider recognition as alternatives to current anticancer treatments. The effectiveness of Auger...
INTRODUCTION
Auger electron emitters, such as (125)I, are getting increasingly wider recognition as alternatives to current anticancer treatments. The effectiveness of Auger electrons is strongly dependent on their proximity to DNA and is therefore considered as harmless outside the nucleus.
METHODS
(125)I or (127)I was conjugated with Comp1, Comp2 or Comp3 - three derivatives of the chemotherapeutic drug daunorubicin. Their capacity factors, DNA-binding constants and exclusion parameters, and the degree of DNA fragmentation after incubating isolated DNA with our (127)I- or (125)I-conjugated daunorubicin derivatives were determined. Human breast adenocarcinoma (SK-BR-3) cells were incubated with the derivatives; fluorescent microscopy and autoradiography images were generated; and cell growth was monitored.
RESULTS AND DISCUSSION
The capacity factor of (127)I-Comp1 was similar to those of daunorubicin and doxorubicin, whereas lower capacity factors of (127)I-Comp2 and (127)I-Comp3 suggested reduced interactions with lipid membranes. DNA exclusion parameters and binding constants of (127)I-Comp1 and (127)I-Comp2, but not of (127)I-Comp3, were similar to those of doxorubicin. Fluorescent microscopy and autoradiography images of SK-BR-3 cells revealed that (127)I-Comp1 and (125)I-Comp1 accumulated in tumor cell nuclei, whereas (127)I-Comp2 and (127)I-Comp3 were present predominantly in other cell compartments. The binding of (125)I-Comp1 to isolated chromosomal DNA led to major fragmentation. Incubation of SK-BR-3 cells with (125)I-Comp1 inhibited cell growth, whereas doxorubicin or (127)I-Comp1 administered at the same concentration had no effect on cell growth. Our results thus suggest that (125)I-Comp1 has the potential to become a new tool for anticancer therapy.
Topics: Cell Line, Tumor; DNA; DNA Fragmentation; Daunorubicin; Humans; Iodine Radioisotopes; Neoplasms; Radiopharmaceuticals; Tissue Distribution
PubMed: 16934696
DOI: 10.1016/j.nucmedbio.2006.06.002 -
Medical and Pediatric Oncology 1992We report the first known case of daunorubicin administered directly into the human central nervous system. A 3 1/2-year-old female with pneumonia and otitis media was...
We report the first known case of daunorubicin administered directly into the human central nervous system. A 3 1/2-year-old female with pneumonia and otitis media was diagnosed with acute lymphoblastic leukemia and was admitted for antibiotics and chemotherapy. On the first day she inadvertently received a 17 mg intrathecal (IT) injection of daunorubicin. When the error was recognized about 1 hour later, her cerebrospinal fluid (CSF) was exchanged with sterile saline by barbotage, IT hydrocortisone was given, a subarachnoid catheter was inserted, and the CSF was allowed to drain for 36 hours. Only 5.6 mg (33%) of the dose was recovered from CSF, 2.7 mg as daunorubicin and 2.9 mg as the metabolite, daunorubicinol. Initially she was asymptomatic and induction therapy continued with vincristine, 1-asparaginase, prednisone, and IT methotrexate. One week after the daunorubicin injection she developed headache and irritability; CSF protein was 3.2 gm/dl. On the 12th day, she developed fungal sepsis and worsening pneumonia. On the 15th day, she became comatose with a flacid paraparesis, areflexia, and an ascending progressive bulbar palsy. A series of computerized tomography scans over 6 weeks showed increasing diffuse cerebral atrophy. Nerve conduction velocity studies were consistent with an axonal neuropathy. Despite her multiple concurrent medical problems, the timing and characteristics of neurologic damage suggest that IT daunorubicin caused progressive destruction of the nervous system.
Topics: Central Nervous System Diseases; Child, Preschool; Daunorubicin; Female; Humans; Injections, Spinal; Precursor Cell Lymphoblastic Leukemia-Lymphoma
PubMed: 1574039
DOI: 10.1002/mpo.2950200315 -
Anticancer Research Dec 2012In the search for new derivatives of anthracycline antibiotics, formamidinodaunorubicins containing in the amidine group either a morpholine moiety (DAUFmor) or a...
BACKGROUND/AIM
In the search for new derivatives of anthracycline antibiotics, formamidinodaunorubicins containing in the amidine group either a morpholine moiety (DAUFmor) or a hexamethyleneimine moiety (DAUFhex) were synthesized. The biological effects of daunorubicin (DAU), DAUFmor and DAUFhex were compared.
MATERIALS AND METHODS
The experiments were performed on human acute lymphoblastic leukemia MOLT-4 cells and human acute myeloblastic leukemia ML-1 cells. The research was conducted using the spectrophotometric 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT) assay and the electronic Beckman-Coulter method.
RESULTS
Temporary changes in the leukemia cell viability, size and count were found. The antileukemic activities of the new DAU analogs were weaker than that of daunorubicin. MOLT-4 cells were more sensitive than ML-1 cells to the action of all agents. Among the formamidinodaunorubicins, DAUFmor appeared to be more active in ML-1 cells than DAUFhex, but there were not differences between the analyzed values in MOLT-4 cells.
CONCLUSION
The structural modifications of daunorubicin were responsible for the different antileukemic potentials of the two formamidinodaunorubicins.
Topics: Antibiotics, Antineoplastic; Cell Line, Tumor; Daunorubicin; Dose-Response Relationship, Drug; Drug Screening Assays, Antitumor; Humans; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Structure-Activity Relationship
PubMed: 23225426
DOI: No ID Found -
Journal of Chromatography. B,... Nov 2001Anthracyclines are among the most widely used anticancer agents. Notwithstanding the large efforts to develop new drugs with a better pharmaceutical profile,... (Review)
Review
Anthracyclines are among the most widely used anticancer agents. Notwithstanding the large efforts to develop new drugs with a better pharmaceutical profile, daunorubicin, doxorubicin, epirubicin and idarubicin are still the most used in clinical practice. Many efforts are now ongoing to reduce the side effects by using pharmaceutical formulations able to release the drug in the most appropriate way and monitoring the quantity of anthracyclines and their metabolites in the body fluids or tissues frequently and in every patient to maintain the drug concentration within the expected range. This review describes the most recent developments in the separation and quantitation of the above clinically useful drugs, together with their principal metabolites. Some less widely used derivatives will also be considered.
Topics: Antibiotics, Antineoplastic; Chromatography, High Pressure Liquid; Daunorubicin; Doxorubicin; Electrophoresis, Capillary; Epirubicin; Idarubicin; Spectrophotometry, Ultraviolet
PubMed: 11817026
DOI: 10.1016/s0378-4347(01)00346-2 -
Advances in Pharmacology and... 1978
Review
Topics: Animals; Anti-Bacterial Agents; Antibiotics, Antineoplastic; Chemical Phenomena; Chemistry; Daunorubicin; Drug Resistance; Humans; Kinetics; Leukemia
PubMed: 358802
DOI: 10.1016/s1054-3589(08)60480-9 -
ACS Applied Materials & Interfaces Nov 2019A novel self-assembling peptide-functionalized core-shell mesoporous silica nanoparticle was developed as a drug carrier. Superparamagnetic manganese- and cobalt-doped...
A novel self-assembling peptide-functionalized core-shell mesoporous silica nanoparticle was developed as a drug carrier. Superparamagnetic manganese- and cobalt-doped iron oxide nanoparticles formed the core for the mesoporous silica shell coating. On the silica outer shell, the peptide Boc-Phe-Phe-Gly-Gly-COOH was covalently conjugated by 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride and -hydroxysulfosuccinimide sodium salt coupling. The self-assembling property of the peptide at physiological temperature was utilized to block the pore openings, while the disassembly at elevated local particle temperature released cargo molecules without bulk heating that would cause cell damage. Both conventional heating and heating in an alternating magnetic field were tested for the release of fluorescein and daunorubicin. In vitro experiments showed high cytotoxicity on pancreatic carcinoma cells (PANC-1) when this delivery system was activated by an alternating magnetic field, while control particles without drugs showed no obvious cytotoxicity.
Topics: Antineoplastic Agents; Cell Line, Tumor; Daunorubicin; Drug Carriers; Drug Delivery Systems; Drug Liberation; Humans; Magnetics; Metal Nanoparticles; Particle Size; Peptides; Porosity; Silicon Dioxide
PubMed: 31661236
DOI: 10.1021/acsami.9b13614 -
Leukemia 1992The pharmacology of ID and IDOL are of interest in light of the potential utility of ID in the treatment of adult and pediatric leukemia patients. Preclinical activity... (Review)
Review
The pharmacology of ID and IDOL are of interest in light of the potential utility of ID in the treatment of adult and pediatric leukemia patients. Preclinical activity and cellular pharmacology of ID were suggestive of greater clinical activity when compared with several standard anthracyclines. Most intriguing were data comparing in vitro and in vivo activity data and cellular pharmacology of IDOL to other anthracycline alcohol metabolites. Given the pharmacokinetics of IDOL, there is continued interest in the unique aspects of IDOL pharmacology as an important element of ID pharmacology.
Topics: Animals; Daunorubicin; Humans; Idarubicin
PubMed: 1548940
DOI: No ID Found -
Folia Microbiologica 19787-Deoxy-13-dihydrodaunomycinone was isolated from three strains of Streptomyces coeruleorubidus. Its production was found to rise at the end of cultivation and to be...
7-Deoxy-13-dihydrodaunomycinone was isolated from three strains of Streptomyces coeruleorubidus. Its production was found to rise at the end of cultivation and to be stimulated by lowered aeration intensity.
Topics: Daunorubicin; Streptomyces
PubMed: 669492
DOI: 10.1007/BF02876587