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1.
Zhonghua Yi Xue Za Zhi ; 87(48): 3399-405, 2007 Dec 25.
Article in Chinese | MEDLINE | ID: mdl-18476538

ABSTRACT

OBJECTIVE: To investigate the effects of uroacitide (CDA-2), a cell differentiation agent, on the growth inhibition and differentiation of imatinib-(IM) resistant chronic myeloid leukemia (CML) cells. METHODS: IM resistant CML cell line K562R was established from the line K562. K562 and K562R CML cells were cultured with CDA-2 of different concentrations. MTI method was used to detect the survival rates. Bone marrow cells of IM-resistant and non-IM-resistant CML patients were collected and co-incubated with K562 and K562R cells. MTT and colony-forming assays were used to evaluate the efficacy of CDA-2 treatment for cell growth in K562 and K562R cell lines, and IM-resistant or non-IM-resistant bone marrow cells of the CML patients; Annexin-V staining was employed to detect the apoptosis. Cell differentiation was assessed by flow cytometry analysis with CD11b/CD14 markers, reverse transcriptase PCR (RT-PCR) for mRNA levels of NCF-1 and ORM-1 genes and Giemsa staining for the observation in morphology. Cell cycle distribution was detected by stained with propidium iodide and then analyzed by flow cytometer. RT-PCR also was employed for the expression of DNA methyltransferase. RESULTS: Significant cell growth inhibition was found at a dose-dependent manner in the IM-resistant K562R cell line and IM-resistant bone marrow cells of the CML patients compared with the non-resistant K562 cell line and bone marrow cells of the CML patients following 7 days exposure to CDA-2. Although CDA-2 could significantly induce the apoptosis of K562R (15.38%) compared with K562 (5.28%) (P < 0.05), the major reason for the cell growth inhibition of K562R is CDA-2-induced cell differentiation, including the increase of expression of differentiation-related antigens CD11b/CD14, mRNA expression of NCF-1 and ORM-1, and cell cycle arrest in G1-phase at a dose-dependent manner. Because CDA-2 could significantly activate the p21 and p27 gene expression, downregulate the expression of cyclin D1, and down-regulate the expressions of DNMT1 and DNMT(3B) at mRNA level, CDA-2 might be a DNMT inhibitor for restoring some gene function that involved in cell cycle control by demethylation. CONCLUSION: Inhibiting the growth and inducing the differentiation of K562R cells, CDA-2 is very likely to be a potential agent for the treatment of IM resistance CML patients.


Subject(s)
Antineoplastic Agents/pharmacology , Antineoplastic Agents/urine , Cell Proliferation/drug effects , Drug Resistance, Neoplasm/drug effects , Apoptosis/drug effects , Benzamides , Blotting, Western , CD11b Antigen/analysis , Flow Cytometry , Humans , Imatinib Mesylate , K562 Cells , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/genetics , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/metabolism , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/pathology , Lipopolysaccharide Receptors/analysis , NADPH Oxidases/genetics , Piperazines/pharmacology , Pyrimidines/pharmacology , RNA, Messenger/genetics , RNA, Messenger/metabolism , Reverse Transcriptase Polymerase Chain Reaction
2.
Zhonghua Zhong Liu Za Zhi ; 28(9): 706-8, 2006 Sep.
Article in Chinese | MEDLINE | ID: mdl-17274381

ABSTRACT

OBJECTIVE: To evaluate the safety of domestically produced idarubicin in the treatment of acute leukemia by a multicenter randomized control trial. METHODS: This trial was carried out in the hemotologica department of five hospitals throughout China, with hospitalized patients who suffered from acute myelogenous leukemia ( AML except M3 type) , acute lymphocytic leukemia ( ALL) , chronic myelogenous leukemia-blast (CML-blast) , totally 155 patients. Those with severely cardial, hepatic or renal disfunction or those who had ever treated with > or = 200 mg/m(2) idarubicin were excluded from the trial. All patients signed the letter of consent as required by the Ethics Committee of our government. In this study, 155 leukemia patients were randomly grouped into: 1. test group treated using domestic idarubicin, 2. control group using imported idarubicin. The acute myelogenous leukemia regimen included idarubicin 8 mg/m(2), dl -3 plus cytosine arabinoside 100 mg/m(2), dl - 7 for 1-2 cycles. The regimen for acute lymphocytic leukemia was idarubicin 8 mg/m2, dl - 3; vincristine 2 mg/mr, dl; cyclophosphamide 750 mg/m2, dl ; plus prednisone 60 mg/m(2),dl - 14 for 1-2 cycles. RESULTS: Clinical response rate of the tested group treated with domestic idarubicin and control group treated with imported idarubicin was 78. 1% (50/64) vs. 76.9% (50/65) without any statistically significant difference between the two groups(P >0. 05). Grade Ill - IV hematological toxicity rate of the domestic idarubicin group and imported idarubicin group was 74. 0% vs. 73. 1% , respectively (P = 0. 73). Drug-related death was observed in 3 of 77 patients in the domestic idarubicin group (3.9%) due to cerebral hemorrage or septic infection. The incidence of non-hematological toxicities in domestic idarubicin group and imported idarubicin group was 84. 4% vs. 79. 5% for nausea or vomiting, 70. 1% vs. 71. 8% for infection, 42. 9% vs. 41. 0% for mucositis, 33. 8% vs. 33. 3% for alopecia, 28.6% vs. 28. 2% for serum glutamicoxalacetic transaminase abnormalitis, 16. 9% vs. 10. 3% for cardiac toxicity, all without statistically significant differences between these two groups (P > 0. 05). Discontinuation of treatment due to non-hematological toxicity was not neccessary. CONCLUSION: Domestic idarubicin is comparable to imported counterpart in efficiency and safety for the treatment of acute leukemia. The most severe side effects of domestic idarubicin is hematological toxicity, which should be closely observed and treated in time, while its non-hematological toxicity is tolerable.


Subject(s)
Antibiotics, Antineoplastic/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Idarubicin/administration & dosage , Leukemia, Myeloid, Acute/drug therapy , Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy , Adolescent , Adult , Aged , Agranulocytosis/chemically induced , Antibiotics, Antineoplastic/adverse effects , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Blast Crisis/drug therapy , Cyclophosphamide/administration & dosage , Cyclophosphamide/adverse effects , Cytarabine/administration & dosage , Cytarabine/adverse effects , Female , Humans , Idarubicin/adverse effects , Male , Middle Aged , Mucositis/chemically induced , Nausea/chemically induced , Prednisone/administration & dosage , Prednisone/adverse effects , Remission Induction , Treatment Outcome , Vincristine/administration & dosage , Vincristine/adverse effects
3.
Zhonghua Zhong Liu Za Zhi ; 27(12): 750-2, 2005 Dec.
Article in Chinese | MEDLINE | ID: mdl-16483490

ABSTRACT

OBJECTIVE: To evaluate the efficacy and safety of IDA (Haizheng Parmacy, China) in the treatment of acute leukemia. METHODS: A multi-institutional single-blind randomized controlled clinical trial was carried out. A total of 155 newly diagnosed patients with AML and ALL were enrolled. The patients were randomly divided into two groups, one was given IDA (n = 77) and the other given zevodas (Pharnacia & Upjohn, n = 78) for comparison. RESULTS: All the patients enrolled in this trial were eligible for assessment of side effects, and 129 patients for evaluation of overall response rate. In patients treated with IDA vs zevodas, the overall response rate (OR) was 78.1% vs 76.9%, CR was 68.8% vs 67.7%; in AML patients, OR was 82.4% vs 71.8%, and CR was 76.5% vs 64.1%; in ALL patients, OR was 80.0% vs 81.8%, and CR was 68.0% vs 68.2%. There was no sitatistically significant difference in hematologic and non-hematologic toxicities between the two groups. CONCLUSION: The efficacy of IDA in the treatment of acute leukemia is comparable to that of zevodas. Both have similar toxic side effects.


Subject(s)
Antibiotics, Antineoplastic/therapeutic use , Idarubicin/therapeutic use , Leukemia, Myeloid, Acute/drug therapy , Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy , Adolescent , Adult , Aged , Antibiotics, Antineoplastic/adverse effects , China , Female , Humans , Idarubicin/adverse effects , Male , Middle Aged , Single-Blind Method
4.
Zhonghua Xue Ye Xue Za Zhi ; 25(9): 548-51, 2004 Sep.
Article in Chinese | MEDLINE | ID: mdl-15569536

ABSTRACT

OBJECTIVE: To study the changes of platelet in May-Hegglin anomaly (MHA) and the molecular pathogenesis mechanism. METHODS: Peripheral blood was drawn from the MHA proband, her father and her uncle. Platelet count and morphology were examined by automatic blood cell counter and microscopy, respectively. The platelet membrane protein was examined by flow cytometry. Membrane antibodies were determined by ELISA. PCR was used to amplify the exons 25, 31 approximately 32, 38 and 40 of the MYH 9 gene in the MHA patient and her diseased father. Furthermore, PCR products were sequenced, a specific point mutation was identified and inclusions (Dohle's body) in the neutrophil was detected by indirect immunofluorescence technique. RESULTS: It was proved that in MHA patients, platelet count was higher by cell counter than by microscope (P < 0.01). Giant platelet was 94% but platelet membrane proteins (CD41, CD61, CD42A, CD42b) were in normal range. Membrane antibodies was undetectable. An A5521G mutation (GAG-->AAG) in the exon 38 was found in the proband and her diseased father, resulting in a characteristic change of NMMHC-A1841 (Glutamic acid-->Arginine), which was not found in other members of the family and in normal controls. Spindle-like inclusions with fluorescence were clearly displayed in neutrophil cytoplasm. CONCLUSION: The molecular pathogenesis mechanism of May-Hegglin anomaly is the mutation in MYH 9 gene.


Subject(s)
Molecular Motor Proteins/genetics , Mutation , Myosin Heavy Chains/genetics , Thrombocytopenia/genetics , Adult , Base Sequence , Blood Platelets/metabolism , Blood Platelets/pathology , DNA Mutational Analysis , Enzyme-Linked Immunosorbent Assay , Female , Flow Cytometry , Granulocytes/metabolism , Granulocytes/pathology , Humans , Inclusion Bodies/metabolism , Inclusion Bodies/pathology , Male , Pedigree , Platelet Count , Platelet Membrane Glycoproteins/metabolism , Thrombocytopenia/blood , Thrombocytopenia/pathology
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