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

The objective of study was to evaluate the efficiency and safety of bortezomib for the treatment of multiple myeloma. Bortezomib in combination with dexamethasone was administered as first-line treatment in all 7 newly diagnosed patients with multiple myeloma. The patients with refractory myeloma were treated with bortezomib in combination with dexamethasone or with other traditional agents such as mitoxantrone and thalidomide. The results showed that according to the EMBT criteria, out of 7 patients one achieved complete response (CR), five achived partial response (PR) and one achived minor response (MR). The 3 patients with refractory/relapsed myeloma achieved PR (2/3) and MR (1/3). The overall response rate (CR + PR) was 80%. The most frequent adverse events observed were thrombocytopenia in three patients, diarrhea and peripheral neuropathy in one respectively. In conclusion, bortezomib demonstrates efficiency in the treatment of new-diagnosed and refractory/relapsed multiple myeloma, and the side effects from treatment are acceptable and manageable.
Adult ; Aged ; Antineoplastic Agents ; administration & dosage ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Boronic Acids ; administration & dosage ; Bortezomib ; Dexamethasone ; administration & dosage ; Female ; Humans ; Male ; Middle Aged ; Multiple Myeloma ; drug therapy ; Protease Inhibitors ; administration & dosage ; Pyrazines ; administration & dosage

In order to evaluate the efficiency of rituximab combined with fludarabine, cyclophosphamide and rituximab (FCR) regimen for chronic lymphocytic leukemia (CLL). Five patients with CLL were treated with FCR regimen for 2 - 6 courses. FCR regimen included fludarabine 25 mg/m(2) via intravenous drip at day 2 - 4, cyclophosphamide 250 mg/m(2) via intravenous drip at day 2 - 4 and rituximab 375 mg/m(2) via intravenous drip at day 1. Courses were repeated every 4 weeks. Minimal residual disease (MRD) was determined by multiparametic flow cytometry. The results showed that three patients achieved complete remission, 2 patients achieved partial remission. MRD was negative in two patients. In conclusion, FCR is an effective therapeutic regimen for treating CLL patients and is worth to be used in clinic.
Adult ; Aged ; Antibodies, Monoclonal ; administration & dosage ; Antibodies, Monoclonal, Murine-Derived ; Antineoplastic Agents ; administration & dosage ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Cyclophosphamide ; administration & dosage ; Female ; Humans ; Leukemia, Lymphocytic, Chronic, B-Cell ; drug therapy ; Male ; Middle Aged ; Remission Induction ; Rituximab ; Vidarabine ; administration & dosage ; analogs & derivatives

The aim of this study was to compare the efficacy of rituximab plus CHOP regimen and CHOP regimen on newly diagnosed patients with diffuse large B-cell lymphoma (DLBCL), and analyze their toxicities. A total of 69 patients were enrolled from July 2003 to Dec 2006. The patients were non-randomly were divided into 2 groups: 36 received CHOP alone (CHOP group) and 33 received rituximab plus CHOP (R-CHOP group). The complete response (CR) rates, overall survival (OS) and side events of the 2 groups were compared. The results showed that the CR rate in R-CHOP group was higher than that in CHOP group (69.7% vs 47.2%, p = 0.049); especially in patients of male, Ann Arbor III - IV and IPI 3 - 5 (p = 0.017, p = 0.005 and p = 0.000). The estimated mean OS in R-CHOP group was longer than that in CHOP group (45.7 months vs 35.2 months, p = 0.145), and also in the estimated mean progression free survival (PFS) (38.5 months vs. 24.6 months, p = 0.017). The major adverse events in combination group were infusion-related responses which could be well tolerated in patients, and hematological toxicities which were similar to those in CHOP group. In conclusions, Rituximab increases the therapeutic efficacy of CHOP regimen on newly diagnosed patients with DLBCL, without a clinically significant increase in toxicity.
Adolescent ; Adult ; Aged ; Antibodies, Monoclonal ; administration & dosage ; adverse effects ; Antibodies, Monoclonal, Murine-Derived ; Antineoplastic Combined Chemotherapy Protocols ; adverse effects ; therapeutic use ; Cyclophosphamide ; adverse effects ; therapeutic use ; Doxorubicin ; adverse effects ; therapeutic use ; Female ; Humans ; Lymphoma, Large B-Cell, Diffuse ; drug therapy ; Male ; Middle Aged ; Prednisone ; adverse effects ; therapeutic use ; Prospective Studies ; Rituximab ; Safety ; Vincristine ; adverse effects ; therapeutic use ; Young Adult

The objective of this study was to investigate the immunophenotypic characteristics of T-cell acute lymphoblastic leukemia (T-ALL). Immunophenotyping was performed in 140 T-ALL patients by flow cytometry using a panel of monoclonal antibodies and CD45/SSC gating. The results showed that the T-lineage-associated antigen expressions were CD7 > CD2 > CD3 > CD5 successively. The positive rate of CD10 was 19.42% in patients. Among 140 cases of T-ALL, 12 (8.57%) was accompanied by B-lineage associated antigen expression. Myeloid antigen expression was identified in 31 out of 136 cases (22.79%). None of them expressed CD14 antigen. The positive rate of CD34 was 31.06%. The positive rate of myeloid antigen expression in CD34(+) T-ALL (36.58%) was significantly higher than that in CD34(-) T-ALL (15.38%) (p < 0.01). The expression of CD3 in child T-ALL was higher than that in adult T-ALL, whereas the expression of CD33 in children was lower than that in adults. It is concluded that immunophenotyping is an important tool for diagnosis of T-ALL. Immunophenotypic characteristics of T-ALL is heterogeneous.
Adolescent ; Adult ; Aged ; Antigens, CD ; metabolism ; Antigens, CD34 ; metabolism ; Antigens, Differentiation, Myelomonocytic ; metabolism ; CD3 Complex ; metabolism ; Child ; Child, Preschool ; Female ; Humans ; Immunophenotyping ; Infant ; Male ; Middle Aged ; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma ; diagnosis ; immunology ; Sialic Acid Binding Ig-like Lectin 3 ; Young Adult

The purpose of this study was to evaluate the efficiency and safety of tandem double autologous peripheral blood stem cell transplants (T-APBSCT) for de novo multiple myeloma (MM) patients. The clinical data of 3 patients treated by T-APBSCT after chemotherapy were analyzed retrospectively. The first mobilization regimen was cyclophosphamide (CTX) combined with G-CSF 5 microg/(kg x d) and the conditioning regimen for the transplantation was 180 mg/m(2) melphalan. The second mobilization regimen was CTX and VP16 in combination with G-CSF 5 microg/(kg x d) and the conditioning regimen for the transplantation was 180 mg/m(2) melphalan or 10 Gy total body irradiation plus 140 mg/m(2) melphalan. The interval of two in tandem autotransplants was 31, 15 and 27 weeks. For two in tandem APBSCT in 3 patients, the cell number of mononuclear cells (MNCs) transfused was 4.7 x 10(8), 2.798 x 10(8), 6.08 x 10(8)/kg and 1.67 x 10(8), 2.798 x 10(8), 4.28 x 10(8)/kg, while the dose for CD34(+) cells were 3.25 x 10(6), 9.6 x 10(6), 5.91 x 10(6)/kg and 6.9 x 10(6), 9.6 x 10(6), 5.91 x 10(6)/kg for their first and second transplants respectively. The results showed that all patients gained prompt and sustained hematopoietic reconstitution. In double tandem transplantation for 3 patients the interval of absolute neutrophil count (ANC) >or= 1 x 10(9)/L were at day 12, 0, 10 and 12, 25, 0; while platelet count >or= 20 x 10(9)/L were at day 12, 0, 10, and 11, 25, 20 days. The median follow-up time for 2 T-APBSCT was 44 (range 19 - 58) months. Two patients survived, one of them was in complete remission and other was in a stable PR stage, but one out 3 patients died at 58 months after T-APBSCT. It is concluded that the method of T-APBSCT for de novo multiple myeloma is probably safe and effective.
Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Granulocyte Colony-Stimulating Factor ; therapeutic use ; Humans ; Male ; Middle Aged ; Multiple Myeloma ; therapy ; Peripheral Blood Stem Cell Transplantation ; methods ; Retrospective Studies ; Transplantation, Autologous