Sample records for aclarubicin

  1. Postincubation with aclarubicin reverses topoisomerase II mediated DNA cleavage, strand breaks, and cytotoxicity induced by VP-16

    Petersen, L N; Jensen, P B; Sørensen, B S


    In previous studies, we found that VP-16 (etoposide) induced cytotoxicity and protein-concealed strand break formation was prevented in a small cell lung cancer (SCLC) cell line, when the cells were incubated with aclarubicin prior to treatment with VP-16. In the present work, we studied the effect...... of adding aclarubicin to the cell suspension after VP-16. In a clonogenic assay, we found that the cytotoxicity induced by VP-16 in SCLC cells was inhibited when cells were postincubated with aclarubicin. The addition of aclarubicin at any time in relation to VP-16 was able to stop further cytotoxicity...... induced by the topoisomerase II (topo-II) targeting drug. Aclarubicin was also found to antagonize the cytotoxicity induced by VM-26 (teniposide), and m-AMSA. With the alkaline elution technique we found that postincubating the cells with aclarubicin inhibited VP-16-induced DNA strand break formation...

  2. Radiotherapy combined with aclarubicin and neocarzinostatin for cancer of the gallbladder

    Okuyama, Shin-ichi; Mishina, Hitoshi; Funaki, Ken-ichi; Mori, Toshihiko (Tohoku Rosai Hospital, Sendai (Japan))


    Cancer of the gallbladder is radioresistant. When it was found inoperable, she was subjected to radiotherapy combined with aclarubicin and neocarzinostatin. Therapeutic effectiveness was confirmed at autopsy as she later succumbed to uterine cervical cancer. Thus, the present radiochemotherapeutic regimen would probably provide a means of overcoming those radioresistant inoperable malignancies. Intravenous administrations of appropriate antibiotics such as azthreonam and reniran may probably be helpful in the prevention and treatment of septic peritonitis possible during the course of reinforced radiotherapy of the abdomen. (author).

  3. Negative-ion chemical-ionization mass spectrometry of aclarubicin analogs and characterization of two metabolites in man

    Smith, R.G.; Miller, A.A.; Benvenuto, J.A.; Valdivieso, M.; Loo, T.L.


    Aclarubicin and seven analogs have been characterized by negative-ion chemical-ionization mass spectrometry. The method is highly sensitive (requires 1-10 ng) because of the stable semiquinone radical anions that are produced by resonance electron capture of thermal electrons. Ions in the spectra correspond to the intact molecule (M), M-H/sub 2/O, aglycone, aglycone-O, and aglycone-2H/sub 2/O. In addition, ions corresponding to the sequential loss of carbohydrate groups are exhibited in the spectra of compounds with di- and tri-saccharides. Two aclarubicin analogs were isolated from a patient's plasma and were found to be bisanhydroaklavinone, F, and one or both of the epimeric reduction products of the L-cinerulose carbonyl, M1 and N1.


    汤洁; 蔡树模; 范建玄


    Objective To study the response rate and toxic side effect of Vindesine, aclarubicin and mitomycin (VAM) as a new regime of second line chemotherapy for ovarian carcinoma refractory to platinum group of drugs.Methods From June 1997 through August 1998, 25 cases of refractory ovarian carcinoma were treated with VAM regime. The response rate and the side reactions were analyzed. Results The overall response rate was 32.0%, with 3 complete response (CR) and 5 partial response (PR). In the platinum refractory, platinum-resistant platinum-senstitive strata, the response rates were 18.2% 28.6% and 57.1% respectively. Myelosuppression was the main toxic effect. Grade 3 and grade 4 neutropenia occurred in 40.0% and thrombocytopenia in 28.0% of the patients. Alopecia occurred in 32% of cases. Gastrointastinal, cardiac and neurologic toxicities were mild. Conclusion VAM regime is a practical and effective second-line chemotherapy for patients with ovarian carcinoma refractory to platinum based chemothrapy.%目的 研究VAM方案作为二线方案治疗耐药卵巢癌的疗效和毒性反应。方法 长春酰胺、阿克拉霉素、丝裂霉素联合应用治疗25例经铂类化疗失败的卵巢癌。结果 完全缓解3例,部分缓解5例,总有效率为32.0%(8/25)。对铂类难治性患者、铂类耐药者和敏感者有效率分别为18.2%、28.6%和57.1%。毒性反应以骨髓抑制为明显,Ⅲ+Ⅳ度白细胞、中性粒细胞和血小板下降分别为40.0%、60.0%和28.0%。胃肠反应、心脏、神经毒性均不严重,脱发占32.0%。结论 VAM方案是当前国内治疗耐铂卵巢癌切实可行的有效方案,值得推广应用。

  5. Efficacy and safety of the HAA regimen as induction chemotherapy in 236 de novo acute myeloid leukemia



    Objective To evaluate the efficacy and safety of the HAA regimen (homoharringtonine,cytarabine and aclarubicin) as induction chemotherapy in de novo acute myeloid leukemia (AML) .Methods The efficacy and safety of 236 de novo AML patients who received the HAA regimen as induction chemotherapy were retrospectively analyzed.The complete remission (CR) rate was assayed.Kaplan-Meier method was used to estimate overall survival (OS) and relapse free survival (RFS) ,and the differ-

  6. Outcomes of CAG Regimen for Refractory Biphenotypic Acute Leukemia Patients

    Guang-sheng He; Xiang Zhang; De-pei Wu; Ai-ning Sun; Zheng-ming Jin; Hui-ying Qiu; Miao Miao; Xiao-wen Tang; Zheng-zheng Fu; Yue Han


    Objective To evaluated the efficiency of low-dose cytosine arabinoside plus aclarubicin with concurrent administration of granulocyte colony-stimulating factor(CAG)regimen for refractory biphenotypic acute leukemia(BAL).Methods We treated 5 refractory BAL patients by CAG regimen(10 mg·m 2 cytosine arabinoside subcutaneously administrated every 12 hours,day 1-14;5-7 mg·m2 aclarubicin intravenously administrated daily,day 1-8;and concurrently used 200 μg.m-2·d-1 granulocyte colony-stimulating factor subcutaneously)from November 2002 to April 2007.The efficacy of the regimen was evaluated by response rate,and the side effects were also measured.Results The complete remission rate was 80% ,median duration of absolute neutrophil count<5.0×108/L and platelet count<2.0×1010/L was day 13 and day 1,respectively;and the infection rate was low(Ⅲ-Ⅳ infection rate,20.00% ).Conclusion CAG regimen as remission induction chemotherapy for BAL patients is effective with a high remission rate and low toxicity.

  7. Binding of anthracycline derivatives to human serum lipoproteins.

    Chassany, O; Urien, S; Claudepierre, P; Bastian, G; Tillement, J P


    The binding of eight anthracycline analogues (including mitoxantrone) to isolated serum lipoproteins (high, low and very low density lipoproteins) was studied in order to elucidate some determinants of their interaction with lipidic structures. Serum lipoproteins were isolated by ultracentrifugation. Drug binding experiments were run by ultrafiltration at 37 degrees C and pH 7.4. Anthracycline concentrations (total and free) were determined by HPLC with fluorometric detection. All the ligands were significantly bound to the three lipoprotein classes, and for each ligand the binding increased as the lipidic fraction of lipoprotein increased. From doxorubicin to iododoxorubicin, there was a tenfold increase in lipoprotein binding (doxorubicin < mitoxantrone < epirubicin < daunorubicin < pirarubicin < aclarubicin < zorubicin < iododoxorubicin). For all the ligands studied, the extent of lipoprotein binding appears to be related to chemical determinants of lipophilicity.

  8. Real-time monitoring of protein conformational changes using a nano-mechanical sensor.

    Livan Alonso-Sarduy

    Full Text Available Proteins can switch between different conformations in response to stimuli, such as pH or temperature variations, or to the binding of ligands. Such plasticity and its kinetics can have a crucial functional role, and their characterization has taken center stage in protein research. As an example, Topoisomerases are particularly interesting enzymes capable of managing tangled and supercoiled double-stranded DNA, thus facilitating many physiological processes. In this work, we describe the use of a cantilever-based nanomotion sensor to characterize the dynamics of human topoisomerase II (Topo II enzymes and their response to different kinds of ligands, such as ATP, which enhance the conformational dynamics. The sensitivity and time resolution of this sensor allow determining quantitatively the correlation between the ATP concentration and the rate of Topo II conformational changes. Furthermore, we show how to rationalize the experimental results in a comprehensive model that takes into account both the physics of the cantilever and the dynamics of the ATPase cycle of the enzyme, shedding light on the kinetics of the process. Finally, we study the effect of aclarubicin, an anticancer drug, demonstrating that it affects directly the Topo II molecule inhibiting its conformational changes. These results pave the way to a new way of studying the intrinsic dynamics of proteins and of protein complexes allowing new applications ranging from fundamental proteomics to drug discovery and development and possibly to clinical practice.

  9. Acute myelogenous leukemia following chemotherapy and radiation for rectal cancer

    Aso, Teijiro; Hirota, Yuichi; Kondou, Seiji; Matsumoto, Isao; Matsuzaka, Toshimitsu; Iwashita, Akinori


    In August 1982, a 44-year-old man was diagnosed as having rectal cancer, histologically diagnosed as well differentiated adenocarcinoma, and abdominoperineal resection and colostomy were performed. Postoperatively, he received chemotherapy with mitomycin C up to a total dose of 100 mg. In September 1986, lung metastasis occurred and he was treated with a combination chemotherapy consisting of cisplatin, pirarubicin and 5-fluorouracil. In the following year, radiation treatment (total: 6900 rad) was given for a recurrent pelvic lesion. Peripheral blood on April 30, 1988, showed anemia, thrombocytopenia and appearance of myeloblasts, and a diagnosis of acute myelogenous leukemia (FAB: M1) was made. Combination chemotherapy (including aclarubicin, vincristine, behenoyl ara-C, daunorubicin, 6-mercaptopurine, cytarabine, etoposide and prednisolone) failed to induce remission and the patient died in June 1988. This case was thought to be one of secondary leukemia occurring after chemotherapy and radiation treatment for rectal cancer. This case clearly indicates the need for a careful follow-up of long-term survivors who have received cancer therapy. (author).

  10. Comparative serum protein binding of anthracycline derivatives.

    Chassany, O; Urien, S; Claudepierre, P; Bastian, G; Tillement, J P


    The binding of doxorubicin, iododoxorubicin, daunorubicin, epirubicin, pirarubicin, zorubicin, aclarubicin, and mitoxantrone to 600 microM human serum albumin and 50 microM alpha 1-acid glycoprotein was studied by ultrafiltration at 37 degrees C and pH 7.4. Anthracycline concentrations (total and free) were determined by high-performance liquid chromatography (HPLC) with fluorometric detection. Binding to albumin (600 microM) varied from 61% (daunorubicin) to 94% (iododoxorubicin). The binding to alpha 1-acid glycoprotein (50 microM) was more variable, ranging from 31% (epirubicin) to 64% (zorubicin), and was essentially related to the hydrophobicity of the derivatives. Simulations showed that the total serum binding varied over a broad range from 71% (doxorubicin) to 96% (iododoxorubicin). We recently reported that the binding to lipoproteins of a series of eight anthracycline analogues could be ascribed to chemicophysical determinants of lipophilicity [2]. The present study was conducted to evaluate in vitro the contribution of albumin and alpha 1-acid glycoprotein to the total serum binding of these drugs.

  11. Effect of low-dose cytarabine, homoharringtonine and granulocyte colony-stimulating factor priming regimen on patients with advanced myelodysplastic syndrome or acute myeloid leukemia transformed from myelodysplastic syndrome.

    Wu, Lingyun; Li, Xiao; Su, Jiying; Chang, Chunkang; He, Qi; Zhang, Xi; Xu, Li; Song, Luxi; Pu, Quan


    A total of 32 patients (25 with advanced MDS and 7 with t-AML) were enrolled in this study to evaluate the efficacy and toxicity of the low-dose cytarabine and homoharringtonine in combination with granulocyte colony-stimulating factor (G-CSF) (CHG protocol) in patients with advanced myelodysplastic syndromes (MDS) or MDS-transformed acute myeloid leukemia (t-AML). All the patients were administered the CHG regimen comprising low-dose cytarabine (25 mg/day, intravenous continuous infusion, days 1-14), homoharringtonine (1 mg/day, intravenous continuous infusion, days 1-14), and G-CSF (300 microg/day, subcutaneous injection, days 0-14, interrupted when the peripheral white blood cell count reached >20 x 10(9)/L). The overall response rate was 71.9% after the administration of one course of the CHG regimen. Of the 32 patients, 15 (46.9%) achieved complete remission (CR) and 8 (25%) achieved partial remission (PR). This regimen was followed by a post-remission therapy that included conventional chemotherapy, when CR was achieved. Of the patients with CR who just received post-remission regimens as homoharringtonine and cytarabine (HA) and daunorubicin and cytarabine (DA) 6 relapsed rapidly and just had a mean 6.1 months of CR. Otherwise, the other 8 out of 14 patients with CR alternatively received subsequent chemotherapy, which combined mitoxantrone, idarubicin, pirarubicin, or aclarubicin with cytarabine. The mean CR duration of the 8 patients had reached 10.6 months, and 5 of the 8 still kept a continuous CR. The median overall survival (OS) was 18.2 months. There were no statistically significant differences for CR, PR, and OS when the patients were grouped by age, blasts in bone marrow, and karyotypes, respectively. No treatment-related deaths were observed. Myelosuppression was mild to moderate, and no severe non-hematological toxicity was observed. Thus, a CHG priming regimen as an induction therapy was well tolerated and effective in patients with advanced MDS

  12. Clinical study of CAG regimen combined Decitabine in treatment of elderly patients with moderate and high risk myelodysplastic syndrome and acute myeloid leukemia%地西他滨联合小剂量化疗治疗老年中高危骨髓增生异常综合征及急性髓系白血病的临床观察

    徐瑜; 沙颖豪; 谢彦晖


    Objective To observe the clinical efficacy and adverse events of treatment for elderly patients with moderate and high-risk myelodysplastic syndrome (MDS) and acute myelocytic leukemia (AMD with Decitabine (25mg/d, d1-3) combined with CAG (G-CSF300ug/d, d4-13; aclarubicin10mg/d, d4,6,8,10,12; Ara-C25mg/d, d4-13) regimen. Methods Decitabine combined with CAG regimen were used to treat 10 elderly patients with MDS and AML. The outcome was evaluated after 1 course of treatment. Results For ten patients, 3/10(30%) achieved completely remission (CR), 4/10 (40%) marrow completely remission (mCR), 1/10 (10%) partial remission (PR). The overall response rate was 80%. Most patients can withstand adverse reactions occurred mainly for the arrest of bone marrow. Conclusion In older patients, medium and high-risk MDS and AML treated with Decitabine combined with CAG regimen is safe and effective.%目的 观察地西他滨联合CAG方案治疗老年中高危MDS及AML的临床疗效及不良反应.方法 应用地西他滨联合CAG方案治疗MDS及AML患者10例.1个疗程后评估疗效.结果 10例患者,其中3例获得完全缓解(CR) 30%,4例为部分缓解(PR) 10%,1例获得骨髓缓解(mCR)40%.总有效率为80%.大多数患者出现了可以耐受的不良反应,主要表现为骨髓抑制.结论 地西他滨联合CAG方案治疗中高危MDS和老年AML有较好的疗效和安全性.

  13. CAG方案治疗中高危骨髓增生异常综合征和急性髓系白血病疗效观察%Clinical observation of the efficacy of CAG regimen for the treatment of intermediate or high risk myelodysplastic syndrome and acute myeloid leukemia

    侯先锋; 刘琼; 苏贵珍; 孙海英


    Objective To observe the efficacy and adverse reactions of CAG regimen ( cytarabine and aclarubicin in combination with granulocyte colony -stimulating factor ) for treatment of intermediate or high risk myelodysplastic syn-drome (MDS) and acute myeloid leukemia (AML).Methods Twenty-eight MDS patients and twenty AML patients received CAG regimen .Then, the resulting efficacy was evaluated after one course of treatment , in which those with posi-tive response was given another course of treatment .Results MDS patients presented 53%of clinical effectiveness , in-cluding 15 cases (53%) with completely remission (CR).AML patients presented 65%of clinical effectiveness, inclu-ding 10 cases (50%) with CR and 3 cases (15%) with partial remission (PR).Most patients reported slight/mild ad-verse events, mainly myelosuppression , which was tolerable .Conclusion CAG regimen is safe and effective to treat in-termediate or high risk MDS and AML with poor prognosis , and its long-term efficacy requires further observation .%目的:观察阿糖胞苷、阿克拉霉素和粒细胞集落刺激因子联合方案( CAG方案)治疗中、高危骨髓增生异常综合征( MDS)和初治急性髓系白血病( AML)的临床疗效及不良反应。方法应用CAG方案治疗中高危MDS 28例和AML 20例,完成1个疗程后评估疗效,治疗失败患者退出观察,有效者继续接受1个疗程治疗,并进行评估。结果28例MDS临床总有效率53%,其中完全缓解15例(53%),部分缓解0例。 AML临床总有效13例(65%),其中完全缓解10例(50%),部分缓解3例(15%)。大部分患者出现了可以耐受的轻微不良反应,主要表现为骨髓抑制。结论 CAG治疗中、高危MDS和预后差的AML安全有效,长期疗效需进一步观察。

  14. Granulocyte colony-stimulating factor inhibits CXCR4/SDF-1α signaling and overcomes stromal-mediated drug resistance in the HL-60 cell line.

    Sheng, Xianfu; Zhong, Hua; Wan, Haixia; Zhong, Jihua; Chen, Fangyuan


    Combining cytarabine, aclarubicin and granulocyte colony-stimulating factor (G-CSF) has demonstrated marked efficacy in the treatment of elderly and relapsed/refractory patients with acute myeloid leukemia (AML); however, the role of G-CSF remains poorly understood. The present study aimed to investigate the ability of G-CSF to overcome stromal-mediated drug resistance and the underlying molecular mechanism. Two types of co-culture models were established in the HS-5 human bone marrow/stromal and HL-60 human promyelocytic leukemia cell lines, in order to imitate the interactions between stromal and leukemia cells in vitro, which is mediated by the stromal cell-derived factor (SDF)-1α signaling axis. In the present study, HL-60 cells were attracted and adhered to HS-5 cells using migration assay and flow cytometry, respectively; however, these interactions were inhibited by treatment with G-CSF and/or the C-X-C chemokine receptor type 4 (CXCR4) antagonist, AMD3100. Co-culture with HS-5 cells, including direct and indirect contact, protected HL-60 cells against spontaneous apoptosis or drug-induced apoptosis; however, these protective effects were disrupted by treatment with G-CSF and/or AMD3100. Notably, G-CSF and/or AMD3100 did not alter cell viability or apoptosis when HL-60 cells were cultured with medium alone. In addition, G-CSF significantly reduced the expression levels of surface CXCR4 protein, total CXCR4 protein and CXCR4 mRNA, and significantly upregulated the expression of microRNA (miR)-146a. Conversely, AMD3100 significantly reduced surface CXCR4 expression levels, but not the total CXCR4, CXCR4 mRNA or miR-146a expression levels. The results of the present study suggested that interfering with the CXCR4/SDF-1α signaling axis via G-CSF inhibited the migration and adhesion of HL-60 cells to HS-5 cells and eliminated HS5 cell-mediated protective effects. Furthermore, G-CSF administration reduced CXCR4 expression levels by upregulating the expression of

  15. Curative effect of decitabine combined with CAG regimen in older patients with acute myeloid leukemia%地西他滨联合CAG治疗老年急性髓系白血病的疗效观察

    于锦香; 蔡冬梅; 王晓雪; 梁颖; 张蕊; 颜晓菁; 何娟; 李艳


    目的 观察地西他滨联合CAG方案治疗老年急性髓系白血病的疗效和安全性.方法 7例老年急性髓系白血病患者应用地西他滨+ CAG方案[地西他滨15 mg/(m2·d),qd,iv,d1-5;阿克拉霉素10 mg/d,qd,iv,d3-6;阿糖胞苷10 mg/m2,q12h,ih,d3-9;G-CSF 300μg,qd,ih d0-9].观察患者疗效及不良反应.结果 2例使用4个疗程,2例使用3个疗程,1例使用2个疗程,2例使用1个疗程,其中2例获完全缓解,4例获部分缓解,1例疾病进展,最后因肺部感染死亡.结论 地西他滨联合CAG方案治疗老年急性髓系白血病,效果良好,安全性高,不良反应少,化疗相关死亡率低.%Objective To investigate the curative effect and safety of decitabine combined with CAG regimen treatment for elderly AML patients. Methods 7 cases of elderly AML patients were treated with decitabine combined with CAG regimen [decitabine 15 mg/(m2?d) ,qd,iv,d1-5 ,aclarubicin 10 mg/d, qd, iv, d3-6 , Ara-c 10 mg/m2 ,ql2h, ih, d3-9 , G-CSF 300 μg, qd, ih, d0.9]. Results 2 cases lasted for 4 courses, and 2 cases for 3 courses, 1 case for 2 courses and 2 cases for 1 course. There were 2 cases of CR,4 cases of PR,1 case of NR(died of lung infection). Conclusion Decitabine combined with CAG regimen is an effective treatment for the elderly AML patients with high safety and low treatment-related mortality.

  16. 地西他滨联合CAG方案治疗骨髓异常综合征临床研究%Clinical Study on the Treatment of Myelodysplastic Syndrome With the Combination of CAG and Decitabine



    目的:研究地西他滨联合CAG(阿克拉霉素、阿糖胞苷及粒细胞刺激因子)方案治疗骨髓异常综合征临床效果。方法选择我院2013年4月1日~2015年10月31日收治的骨髓异常综合征患者42例作为研究对象,将患者分为两组,观察组21例和对照组21例,观察组患者应用地西他滨联合CAG方案进行治疗,对照组患者应用CAG方案进行治疗,比较两组的治疗效果。结果观察组不良反应发生率比对照组低,差异有统计学意义(P<0.05);观察组治疗有效率比对照组高,差异有统计学意义(P<0.05)。结论地西他滨联合CAG方案治疗骨髓异常综合征临床效果较好。%Objective To study the treatment of Myelodysplastic Syndrome with the combination of Decitabine and CAG(aclarubicin,cytarabine and Granulocyte Colony-Stimulating Factor).Methods Selected 42 patients with myelodysplastic syndrome treated from April 1st,2013 to October 31st,2015,as the research object,and divided the patients into two groups. Observation group 21 cases and the control group 21 cases,observation group of patients with application of Decitabine and CAG,patients in the control group used the CAG solution for treatment,then compared two groups of treatment effect.ResultsThe effective rate of the observation group was lower than the control group,the difference was significant(P<0.05). The incidence of adverse reactions of the observation group was higher than the control group,the difference was significant(P<0.05). Conclusion The efficacy of decitabine combined with CAG in the treatment of myelodysplastic syndrome is significantly.

  17. [Comparison of clinical efficacy between decitabine combined with CAG regimen and CAG regimen alone in patients with intermediate to high-risk myelodysplastic syndromes].

    Zhang, Yun-Ping; Wu, Wen-Zhong; Cui, Guo-Xing


    This study was purposed to compare the clinical efficacy and adverse reactions of low-dose decitabine combined with CAG regimen (aclarubicin, Ara-C, and G-CSF) and CAG regimen alone in intermediate to high-risk myelodysplastic syndromes (MDS), and evaluate the validity and efficacy of the former regimen as new treatment method of intermediate to high-risk myelodysplastic syndromes. A total of 12 patients with intermediate (IR) to high-risk (HR) MDS treated by low-dose decitabine combined with CAG regimen and 10 patients with IR to HR MDS treated by CAG regimen alone were evaluated after treatment of 1 cycle and at least after 2 cycles. The complete remission (CR) after 1 cycle, overall remission rate (ORR), progression free survival (PFS) and overall survival (OS) between them were analyzed. The results showed that 9 patients treated by low-dose decitabine combined with CAG regimen achieved complete remission after 1 cycle, 2 patients achieved partial remission, 1 patient did not show reaction. The complete remission rate was 75.0% and overall response rate was 91.7%. The median time of disease free survival was 9 months (0-27 months). The median overall survival time was 16 months (3-28 months). 4 patients suffered from pulmonary infection after treatment and then were all cured after treatment with anti-infective therapy. The 5 patients treated by CAG regimen alone achieved complete remission,3 patients achieved partial remission, 2 patients showed non-reaction. The complete remission rate was 50.0% and overall response rate was 80.0%. The median time of disease free survival was 6 months(0-18 months). The median overall survival time was 13 months(3-31 months), 4 patients suffered from pulmonary infection, 1 patient suffered from enteric infection and 1 patient suffered from Escherichia coli septicemia after treatment, all of them becomed better after active treatment. Two groups of patients all had no serious adverse reactions, All patients could tolerate, no

  18. The mechanism of different priming protocols inducing apoptosis of leukemia cell lines in vitro%不同预激方案诱导白血病细胞株凋亡的机制研究

    蔡佳翌; 陈芳源; 钟济华; 倪蓓文; 钟华; 王海嵘


    Objective: To investigate the effects of different priming protocols on acute myeloid leukemia (AML) cell line HL-60 and acute monocytic leukemia (AMOL) cell line U937 in vitro, and to explore the possible mechanism.Methods: Both of HL-60 and U937 cells were treated with eight protocols, respectively, including with no drugs (as the control), single cytosine arabinoside (Ara-C),single aclarubicin (Acla), single mitoxantrone (Mito), CA regimen (Ara-C+Acla), MA regimen (Mito+Ara-C), CAG regimen [granulocyte-colony stimulating factor (G-CSF) priming combined with Ara-C and Acla]and MAG regimen (G-CSF priming combined with Mito and Ara-C).The morphological changes of HL-60 and U937 cells were observed after different treatment modalities for 24 and 48 h, respectively.The growth inhibition rates of HL-60 and U937 cells were determined by cell count kit-8 assay.The apoptosis rate, the expression rate of cellular surface specific antigen CD1 1b, the apoptosis-associated mitochondrial membrane potential (by JC-1 method) and the activity of caspase-3 were determined by flow cytometry.Results: After treatment with CAG or MAG regimen for 48 h, the morphology of HL-60 and U937 cells showed that the apoptotic bodies were increased.The growth of HL-60 and U937 cells was all inhibited in different drug-using groups, and the cell survival rates in CAG and MAG regimen groups were significantly decreased in a time-dependent manner.Except for the single Ara-C group, the apoptosis rates of U937 cells were higher than those of HL-60 cells in the other different drug-using groups, but the CD1 1 b expression rate was similar.The mitochondrial membrane potentials of HL-60 and U937 cells were decreased by CAG or MAG regimen induction, and this effect was stronger in CAG or MAG regimen group than in the single-drug groups and the control group (P<0.05).The fluorescence intensities of caspase-3 in CAG and MAG regimen groups and the single-drug groups were higher than that in the control

  19. Research progress on cardio-protective drug for preventing anthracycline cardiotoxicity%蒽环类药物心脏毒性防治药物研究进展

    曲敬琨; 张佳; 张靖; 王健生


    Anthracyclines, which include doxorubicin, epirubicin, daunorubicin, and aclarubicin, are widely used chemotherapeu-tic agents for treating hematologic and solid tumors, such as acute leukemia, lymphoma, breast cancer, gastric cancer, soft tissue sarco-mas, and ovarian cancer. Anthracyclines can be combined with other chemotherapeutics and molecular targeted drugs for cancer treat-ment. The combination of anthracyclines with other chemotherapeutic drugs is usually the standard of first-line treatment. Anthracy-clines are efficacious and potent agents with broad antitumor effects. However, these drugs may cause adverse reactions, such as hair loss, myelotoxicity, and cardiotoxicity. Hematopoietic stimulating factors, such as granulocyte colony-stimulating factor, erythropoietin, and thrombopoietin, can be used to control myelotoxicity. However, cardiotoxicity is the most serious anthracycline side effect. Clinical study results and practical observations indicate that the anthracycline cardiotoxicity is usually progressive and irreversible, especially after the first use of the drug, which may particularly cause heart damage. Therefore, the early detection and prevention of anthracy-cline-induced cardiotoxicity are important and have already gained considerable attention in clinical applications. Relevant experts from the China Society of Clinical Oncology and Hematology Branch of the Chinese Medical Association prepared the guidelines for the pre-vention and cure of anthracycline-induced cardiotoxicity in 2013. The authors reviewed the effective drugs currently used to prevent and cure anthracycline cardiotoxicity.%蒽环类药物包括阿霉素、表阿霉素、柔红霉素和阿克拉霉素等,广泛地用于治疗血液系统恶性肿瘤和实体肿瘤,如急性白血病、淋巴瘤、乳腺癌、胃癌、软组织肉瘤和卵巢癌等。蒽环类药物可以与其他化疗药物及分子靶向药物联合应用,以蒽环类药物为基础的联合治疗

  20. Elderly hematic myeloid tumor patients treated with decitabine and reduced-dose CAG regimen%地西他滨联合减量CAG方案治疗老年血液髓系肿瘤

    黄涛; 刘德斌


    Objective:To study the curative effect and safety of decitabine and reduced-dose CAG regimen for elderly hematic myeloid tumor patients.Methods:10 cases of elderly hematic myeloid tumor patients were treated with decitabine and reduced-dose CAG regimen[decit-abine 15-20mg/(m2· d),qd,iv,d1-5;aclarubicin 10mg/d,qd,iv,d1-4;Ara-C 10mg/m2,q12h,iv,d1-10;G-CSF 300ug/d,qd,ih,d1-10].Results:1 case lasted for 6 courses,and 2 cases lasted for 4 courses,4 cases lasted for 3 courses,and 2 cases lasted for 2 courses,1 case las-ted for 1 course.There were 3 cases of CR(1 case of MDS,2 cases of AML),5 cases of PR(3 cases of MDS,2 cases of AML),2 cases of NR(1 case of AML,1 case of MDS/MPD,died of lung infection).Conclusion:Decitabine and reduced-dose CAG regimen should be an effective treat-ment of the elderly hematic myeloid tumor patients with high safety and tolerable treatment-related mortality.%目的:观察地西他滨联合减量CAG方案治疗老年血液髓系肿瘤的疗效和安全性。方法:10例老年血液髓系肿瘤患者应用地西他滨+减量CAG方案[地西他滨15~20mg/(m2· d),1天1次静注,d1~5;阿克拉霉素10mg/d,1天1次静注,d1~4;阿糖胞苷10mg/m2,12小时1次,静注,d1~10;G-CSF 300ug/d,1天1次,皮下注射,d1~10]。观察患者疗效及不良反应。结果:1例使用6个疗程,2例使用4个疗程,4例使用3个疗程,2例使用2个疗程,1例使用1个疗程,其中3例获完全缓解(1例MDS,2例AML),5例获部分缓解(3例MDS,2例AML),2例疾病进展(1例AML,1例MDS/MPD),最后因肺部感染死亡。结论:地西他滨联合减量CAG方案治疗老年血液髓系肿瘤,疗效良好,不良反应可耐受,值得尽早应用。