Azacitidine ; analogs & derivatives ; therapeutic use ; Clinical Trials, Phase III as Topic ; Humans ; Leukemia, Myeloid, Acute ; drug therapy ; Multicenter Studies as Topic

OBJECTIVE To determine the characterization, anti-tumor efficacy and pharmacokinetics of bufalin- loaded PEGylated liposomes compared with bufalin entity. METHODS Bufalin- loaded PEGylated liposomes and bufalin- loaded liposomes were prepared reproducibly with homogeneous particle size by the combination of thin film evaporation method and high pressure homogenization method. The particle size and zeta potential of the liposomes were determined by dynamic light scattering technique. The direct imaging of morphology of liposomes was charactered by transmission electron microscope. The content of bufalin in liposomes was analysed by HPLC method. The entrapment efficiency and the particle size was applied to assess the stability profile, after storage at 4℃ on day 0, 7, 15, 30 and 90. The in-vitro release behaviours of bufalin from liposomes were conducted using dialysis bag technique at 37℃. In-vitro cytotoxicity studies were carried out using MTT〔3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide〕assay on several kinds of tumor cell lines including SW620, PC-3, MDA-MB-231, A549, U251, U87 and HepG2. In-vivo pharmacokinetic study of bufalin liposomes was evaluated by HPLC method. RESULTS Their mean particle sizes were 127.6 nm and 155.0 nm, mean zeta potentials were 2.24 mV and - 18.5 mV, entrapment efficiencies were 76.31% and 78.40% , respectively. In- vitro release profile revealed that the release of bufalin in bufalin- loaded PEGylated liposomes was slower than that of bufalin-loaded liposomes. The cytotoxicity of blank liposomes has been found within acceptable range, whereas bufalin-loaded PEGylated liposomes showed enhanced cytotoxicity to U251 cells compared with bufalin entity. In-vivo pharmacokinetics indicated that bufalin-loaded PEGylated liposomes could extend eliminate half-life time of bufalin in plasma in rats. CONCLUSION The results suggested that bufalin-loaded PEGylated liposomes improved the solubility and increased the drug concentration in plasma.

The transcriptional coactivator MN1 has been identified as a gene overexpressed in certain types of human acute myeloid leukemia. Overexpression of this gene is associated with all inv (16) AML, retinoic acid-resistance, a worse prognosis as well as a shorter survival in AML patients with a normal karyotype. This article reviews the role of MN1 in acute myeloid leukemia including MN1 gene structure and action mechanism, MN1-TEL and AML with normal karyotype, MN1 and inv (16) AML, MN1 and retinoic ocid-resistance, and so on.
Humans ; Leukemia, Myeloid, Acute ; genetics ; Oncogene Proteins, Fusion ; genetics ; Transcription Factors ; genetics ; Tumor Suppressor Proteins ; genetics

The objective of this study was to evaluate the efficacy and toxicity of the fludarabine combination with high-dose cytarabine (Ara C), idarubicin and granulocyte colony-stimulating factor (G-CSF) (IDA-FLAG regimen) in treatment of refractory/relapsed acute leukemia (AL) patients. 4 patients were male aged from 32 to 44 years, consisted of 3 cases of acute myeloid leukaemia (AML) and 1 cases of acute lymphocytic leukaemia (ALL). All the patients were treated with idarubicin (10 - 12 mg/m(2)/d, days 1 to 3), fludarabine (50 mg/d, days 1 to 5), cytarabine (2 g/m(2)/d, days 1 to 5) and granulocyte colony-stimulating factor (G-CSF, 300 microg/d, days 0 to 5). The results showed that after one course of induction therapy, 4 patients all achieved complete remission (CR), in which 2 patients were in continuous CR after a follow-up of 3 and 4 months; 1 patient relapsed after 10 months and another one patient died of thrombotic thrombocytopenic purpura at 4 months after allogeneic peripheral blood stem cell transplantation. Myelosuppression and infections due to neutropenia were the most frequent adverse effects, severe nonhematologic toxicity and the early death were not observed in these patients. In conclusion, the IDA-FLAG regimen is effective in treatment of patients with refractory and relapsed AL, the adverse effects from this regimen were well tolerated by patients, which gains time for further treatment.
Adult ; Antineoplastic Combined Chemotherapy Protocols ; administration & dosage ; therapeutic use ; Cytarabine ; therapeutic use ; Granulocyte Colony-Stimulating Factor ; therapeutic use ; Humans ; Idarubicin ; therapeutic use ; Leukemia ; drug therapy ; Leukemia, Myeloid, Acute ; drug therapy ; Male ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; drug therapy ; Vidarabine ; analogs & derivatives ; therapeutic use

This study was purposed to investigate the mutational status of DNA methyltransferase (DNMT3a) gene and the clinical features of AML patients with DNMT3a mutations. Using PCR combined with directly sequencing, the somatic mutations of DNMT3a involving residue of amino acid 882 were detected in 77 AML patients. Furthermore, the clinical features of these patients were also studied. The results showed that the DNMT3a mutation were detected in 7 out of 59 patients with de novo AML (11.9%), which included 4 patients with DNMT3a R882C, 2 patients with DNMT3a R882H and 1 patient with DNMT3a Y874C. Morphology examination indicated that 2 patients were M(2), 1 patient was M(4) and 4 patients were M(5). Cytogenetic analysis revealed that karyotype in 5 out of 7 patients with DNMT3a mutation were normal. In total of 27 patients with normal karyotype 5 patients (22.7%) were found harboring DNMT3a mutation, while no DNMT3a mutation was found in 21 patients with abnormal karyotype. The mutation rate in patients with positive CEBPA was obviously higher than that in patients with negative CEBPA (p = 0.002). Immunophenotype analysis showed that 4 patients (4/7, 57.1%) with DNMT3a mutation expressed lymphoid antigens including CD4 or/and CD7. There were no statistical significance in age, gender, blast cells of bone marrow, white blood cell and platelet counts, hemoglobin level, ratio of CR, mutations of FLT3-ITD, NPM1 and c-kit between patients with DNMT3a mutation and patients with wild DNMT3a (p > 0.05). It is concluded that the DNMT3a mutations are more prevalent in AML patients with normal karyotype accompanying with positive NPM1 and/or CEBPA mutation, the role of DNMT3a mutation in AML prognosis needs to be further studied.
Adolescent ; Adult ; Aged ; Aged, 80 and over ; CCAAT-Enhancer-Binding Proteins ; genetics ; Child ; DNA (Cytosine-5-)-Methyltransferases ; genetics ; Female ; Humans ; Leukemia, Myeloid, Acute ; genetics ; Male ; Middle Aged ; Mutation ; Nuclear Proteins ; genetics ; Young Adult

This study was aimed to investigate the therapeutic efficacy and adverse events of bortezomib-based chemotherapy for 40 patients with multiple myeloma. 16 newly diagnosed patients and 11 patients with refractory/relapse myeloma were treated with bortezomib, dexamethasone and thalidomide; 7 newly diagnosed patients and 4 patients with refractory/relapse myeloma were treated with bortezomib and dexamethasone; 2 newly diagnosed patients were treated with bortezomib, melphalan and thalidomide. Cycles were repeated every 28 or 35 days, all the patients were treated for 2 to 8 cycles. The therapeutic efficacy and adverse events were evaluated according to International Myeloma Working Group Uniform Response Criteria. The results indicated that the median follow-up duration was 13 months, the total response rate was 72.5%, among which 16 patients achieved complete response (CR), 13 achieved partial response (PR). The main side effects included gastrointestinal symptoms, peripheral neuropathy, thrombocytopenia, respiratory infection, herpes zoster and urinary retention and so on. The adverse events were ameliorated by treatment and decrease of the bortezomib dose. It is concluded that bortezomib-based chemotherapy is effective in the treatment of either newly diagnosed or refractory/relapse MM patients and the adverse events are tolerable and manageable for patients.
Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols ; adverse effects ; therapeutic use ; Boronic Acids ; administration & dosage ; adverse effects ; Bortezomib ; Female ; Humans ; Male ; Middle Aged ; Multiple Myeloma ; drug therapy ; Pyrazines ; administration & dosage ; adverse effects ; Treatment Outcome ; Young Adult

This study was aimed to evaluate the efficacy and safety of dasatinib in BCR/ABL positive leukemia patients with primary or secondary resistance to imatinib. 27 patients with primary or secondary imatinib-resistant chronic myelogenous leukemia (CML) or Philadelphia chromosome positive acute lymphocytic leukemia (Ph(+) ALL) received 100 - 140 mg/d dasatinib orally. Their overall survival and tolerance were evaluated. The results showed that the median duration of dasatinib therapy was 8 (1-66) months in the 27 imatinib-resistant BCR/ABL positive leukemia cases, with a median follow-up of 54 (3-75) months. After the dasatinib treatment, 88.8% of all the 27 cases achieved complete hematologic response (CHR), 29.6% of them achieved major cytogenetic response (mCyR), 37% of all achieved complete cytogenetic response (CCyR) and 18.5% cases achieved major molecular response (MMR). Patients who received dasatinib in progress of disease (CML-AP, CML-BC and bone marrow relapse Ph(+) ALL) had a lower CCyR rate than those in stable disease (CML-CP and bone marrow remission Ph(+) ALL) (P = 0.0377), and 3 - 4 grade adverse events occurred more frequently in progress of disease than that in stable disease. Overall survival of the patients who achieved CCyR after dasatinib therapy was statistically longer than those who did not achieve CCyR (63 m vs 9 m, P = 0.0126). The most common grade 3 - 4 adverse events during dasatinib therapy including hematology events such as thrombocytopenia (51.8%), neutropenia (48.1%), anemia (33.3%), and non-hematologic events such as pleural effusion (18.5%), pulmonary infection (18.5%), pericardial effusion (11.1%). The 3-4 grade adverse events occurred within 12 months from dasatinib therapy, and were mainly observed in patients with progress of disease. It is concluded that dasatinib is an effective drug in imatinib-resistant BCR/ABL positive leukemia patients, the better curative effect and better tolerance has been observed in patients who received dasatinib in stable disease.
Adult ; Aged ; Benzamides ; therapeutic use ; Dasatinib ; Drug Resistance, Neoplasm ; Female ; Fusion Proteins, bcr-abl ; Humans ; Imatinib Mesylate ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive ; blood ; drug therapy ; Male ; Middle Aged ; Piperazines ; therapeutic use ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; blood ; drug therapy ; Protein Kinase Inhibitors ; therapeutic use ; Pyrimidines ; therapeutic use ; Thiazoles ; therapeutic use ; Treatment Outcome ; Young Adult

To evaluate the efficacy and toxicity of low-dose cytarabine and aclarubicin in combination with granulocyte colony-stimulating factor (G-CSF) protocol for patients with relapsed acute myeloid leukemia (AML). A total of fifty relapsed patients have been enrolled, including 13 early relapsed and 37 late relapsed. 24 patients were male and 26 were female, with age ranging from 15 to 69 (median 47) years. Out of them, 7 patients relapsed after allogeneic peripheral blood stem cell transplantation (allo-PBSCT), 3 patients relapsed after autologous peripheral blood stem cell transplantation (auto-PBSCT), 25 patients relapsed after received regimens including high dose cytarabine and 15 patients relapsed after CR or stopping chemical therapy themself in course of consolidatory therapy. 30 relapsed patients received CAG regimen, and 20 patients (control group) received an anthracycline in combination with cytarabine. The results indicated that after one course, the complete remission (CR) rate was 46.7% (14/30), the CR rate after allo-PBSCT was 50% (3/6), the early death rate was 3.3% in CAG group; and CR rate was 30% (6/20) and the early death rate was 15% in control group. Myelosuppression was mild to moderate, and no severe nonhematologic toxicity was observed in two groups. The overall median times in CAG group and control group were 22 and 19 months respectively. In conclusion, CAG regimen as the induction therapy is effective and well tolerable with low side effects for relapsed patients who had received high dose cytarabine, auto-PBSCT or allo-PBSCT.
Aclarubicin ; administration & dosage ; Adolescent ; Adult ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Cytarabine ; administration & dosage ; Female ; Granulocyte Colony-Stimulating Factor ; administration & dosage ; Humans ; Leukemia, Myeloid, Acute ; drug therapy ; Male ; Middle Aged ; Recurrence ; Treatment Outcome ; Young Adult

This study was aimed to investigate the effect of FLAG consolidatory therapy on peripheral blood stem cell (PBSC) mobilization in patients with acute myelogenous leukemia (AML) for autologous PBSC transplantation. A total of 15 AML patients were enrolled in this study. 10 patients were male, and 5 were female, with ages ranging from 14 to 51 (median 36) years. Out of 15 patients 13 were newly diagnosed, and 2 were refractory/relapsed AML. All patients were consolidated with FLAG regimen which including fludarabine 50 mg/d, days 1-5; Ara-C 2 g/(m2.d), days 1-5; G-CSF 300 microg/d, injection subcutaneously starting 24 hours before Ara-C and continuing until neutrophil count exceeding 1.0x10(9)/L. The harvest of the stem cells was performed after hematologic recovery from the second or third course of FLAG consolidation, or mobilized by high dose etoposide (1.6 g/m2). The results showed that among 15 patients scheduled for PBSC harvest, 11 (73.3%) harvested a median of 3.52x10(6)/kg CD34+ cells (range 2.2-4.6) and underwent autologous transplantation, while the minimal number of CD34+ cells could not be reached in the remaining 4 patients. It is concluded that the FLAG regimen is effective and well-tolerated treatment as consolidation regimen in AML, which does not influence PBSC mobilization and autologous transplantation after 2 courses of FLAG.
Adolescent ; Adult ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Cytarabine ; administration & dosage ; therapeutic use ; Female ; Granulocyte Colony-Stimulating Factor ; therapeutic use ; Hematopoietic Stem Cell Mobilization ; Humans ; Leukemia, Myeloid, Acute ; drug therapy ; therapy ; Male ; Middle Aged ; Peripheral Blood Stem Cell Transplantation ; methods ; Transplantation, Autologous ; Vidarabine ; administration & dosage ; analogs & derivatives ; therapeutic use ; Young Adult

This study was aimed to establish the technique of interphase fluorescence in situ hybridization (I-FISH) used on smear of bone marrow directly, and to develop a new method for detection of the molecular cytogenetics in multiple myeloma (MM). After a series of treatment, fixation and digestion of the bone marrow smear as the carrier, the chromosome 8 centromere probe were used in I-FISH for molecular cytogenetics detection. At the same time, differences were compared in the results between the new method and the conventional I-FISH. The results showed that there was no statistically significant difference of proportion of various signals in non-hematologic malignancies when detected with the two methods (p>0.05). In bone marrow smear I-FISH, 8 out of 19 cases (42.1%) had abnormality of chromosome 8, including 5 cases with -8 (26.3%) and 3 cases with +8 (15.8%). It is concluded that the I-FISH on smear of bone marrow is characterized by convenience, economy and accuracy. Therefore, it can be used for research of molecular cytogenetics in MM.
Adult ; Aged ; Bone Marrow ; pathology ; Chromosome Aberrations ; Chromosomes, Human, Pair 8 ; genetics ; Female ; Humans ; In Situ Hybridization, Fluorescence ; methods ; Male ; Middle Aged ; Multiple Myeloma ; genetics ; pathology