A multicenter, randomized, controlled, phase Ⅲ clinical study of PEG-rhG-CSF for preventing chemotherapy-induced neutropenia in patients with breast cancer and non-small cell lung cancer / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To explore the safety and efficacy of pegylated recombinant human granulocyte colony-stimulating factor (PEG-rhG-CSF) in preventing chemotherapy-induced neutropenia in patients with breast cancer and non-small cell lung cancer (NSCLC), and to provide the basis for clinical application.</p><p><b>METHODS</b>According to the principle of open-label, randomized, parallel-group controlled clinical trial, all patients were randomized by 1∶1∶1 into three groups to receive PEG-rhG-CSF 100 μg/kg, PEG-rhG-CSF 6 mg, or rhG-CSF 5 μg/kg, respectively. The patients with breast cancer received two chemotherapy cycles, and the NSCLC patients received 1-2 cycles of chemotherapy according to their condition. All patients were treated with the combination chemotherapy of TAC (docetaxel+ epirubicin+ cyclophosphamide) or TA (docetaxel+ epirubicin), or the chemotherapy of docetaxel combined with carboplatin, with a 21 day cycle.</p><p><b>RESULTS</b>The duration of grade 3-4 neutropenia in the PEG-rhG-CSF 100 μg/kg and PEG-rhG-CSF 6 mg groups were similar with that in the rhG-CSF 5 μg/kg group (P>0.05 for all). The incidence rate of grade 3-4 neutropenia in the PEG-rhG-CSF 100 μg/kg group, PEG-rhG-CSF 6 mg group, and G-CSF 5 μg/kg group were 69.7%, 68.4%, and 69.5%, respectively, with a non-significant difference among the three groups (P=0.963). The incidence rate of febrile neutropenia in the PEG-rhG-CSF 100 μg/kg group, PEG-rhG-CSF 6 mg group and G-CSF 5 μg/kg group were 6.1%, 6.4%, and 5.5%, respectively, showing no significant difference among them (P=0.935). The incidence rate of adverse events in the PEG-rhG-CSF 100 μg/kg group, PEG-rhG-CSF 6 mg group and G-CSF 5 μg / kg group were 6.7%, 4.1%, and 5.5%, respectively, showing a non-significant difference among them (P=0.581).</p><p><b>CONCLUSIONS</b>In patients with breast cancer and non-small cell lung cancer (NSCLC) undergoing TAC/TA chemotherapy, a single 100 μg/kg injection or a single fixed 6 mg dose of PEG-rhG-CSF at 48 hours after chemotherapy show definite therapeutic effect with a low incidence of adverse events and mild adverse reactions. Compared with the continuous daily injection of rhG-CSF 5 μg/kg/d, a single 100 μg/kg injection or a single fixed 6 mg dose of PEG-rhG-CSF has similar effect and is more advantageous in preventing chemotherapy-induced neutropenia.</p>

DADS induces G2/M arrest through Chk1/Cdc25C/CyclinB1/CDK1 pathway in human leukemia HL-60 cells / 中国药理学通报

Aim To study the effects of cycle arrest and molecular mechanism in human leukemia HL-60 cells induced by diallyl disulfide ( DADS ) . Methods Cell count, colony formation in soft agar experiments and flow cytometry analysis were employed to observe the DADS-induced cell growth inhibition and the effect of cycle arrest in HL-60 cells. The expressions of Chk1/2 and its downstream element in HL-60 cells were detected by Western blot. Results Cell count revealed that population doubling time increased to 35. 03 h and 71. 82 h, respectively, from 19. 14 h in HL-60 cells treated with 60 and 120 μmol·L-1 DADS ( P0. 05). The expression of Cdc25C, CyclinB1 and CDK1 decreased after treated with 60 μmol·L-1 DADS in a time-dependent manner ( P0. 05 ) . Conclusion DADS can in-hibit the proliferation of HL-60 cells, and induce G2/M arrest through Chk1/Cdc25 C/CyclinB1/CDK1 path-way.

Diallyl disulfide induces apoptosis in human leukemia K562 cells through activation of NADPH oxidase / 中国药理学通报

Aim Toresearchthemolecularmecha-nisms of DADS-induced apoptosis in human leukemia K562cells.Methods Cellviabilitywasmeasuredby MTT. Levels of DADS-induced ROS were measured by 2ˊ, 7ˊ-dichlorofluorescein diacetate ( DCFH-DA) fluo-rescence. DADS-induced mRNA levels of components of the NADPH oxidase were detected by Real-time PCR. The combination of protein Rac2 and p67phox was measured by immunoprecipitation assays. Flow cy-tometry methods were used to determine the percentage of apoptosis cells. DADS-induced Rac2 levels were measuredbyWesternblot.Results TheDADS-trea-ted K562 cells showed a dose-and time-dependent de-crease in cell viability and proliferation. There was sig-nificant up-regulation of the mRNA level of components of the NADPH oxidase complex in K562 cells after treatment with 6 mg·L-1 DADS for 6 h. Western blot results revealed that, compared with the control group, there was a significant up-regulation of Rac2 protein in K562 cells treated with 5. 0 and 10. 0 mg·L-1 DADS for 24h. And Rac2 combined with p67phox in DADS-induced apoptosis in K562 cells. PMA markedly in-creased the percentage of apoptotic cells, and DPI re-duced the percentage of apoptotic cells in DADS-in-duced K562 cells. Levels of DADS-induced ROS, also showed enhancement when exposed in PMA, but there was no DADS-induced ROS production evident when exposed in DPI in DADS induced K562 cells. Conclu-sions TheseresultsindicatethatNADPHoxidaseis the main source of DADS-induced ROS production. Diallyl disulfide induces apoptosis in human leukemia K562 cells through activation of NADPH oxidase.

Change of inflammatory factors and its effect on prognosis in patients undergoing acute myocardial infarction thrombolysis treatment / 中国医师进修杂志

ObjectiveTo explore the inflammatory factors C-reactive protein (CRP),interleukin (IL)-6,tumor necrosis factor (TNF)-α and white blood cell (WBC) count differences between acute myocardial infarction(AMI ) thrombolysis treatment and unthormbolysis treatment,and find out the relevance between the inflammatory factors and the prognosis.MethodsAccording to the condition of accepting AMI thrombolysis treatment,the 229 patients of AMI were divided into the thrombolysis group( 131 cases) and the unthrombolysis group(98 cases).The levels of myocardial troponin I (cTnI),creatine kinase(CK),creatine kinase isoenzyme-MB (CK-MB) were detected at the time of patients sent into the hospital for the immediate,6-hour later and 24-hour later.After 6-month's follow-up,prognosis was compared between two groups.ResultsTwenty-seven cases lost in the thrombolysis group.One case died within 6 months and the mortality was 1.0％(1/104) in the thrombolysis group,and 6 cases died within 6 months and the mortality was 6.1％(6/98 ) in the unthrombolysis group.There was significant difference between two groups (P ＜ 0.05 ).The levels of CK,CK-MB in the thrombolysis group advanced,and compared with that in the unthrombolysis group,there were significant differences (P ＜ 0.05 ).The levels of TNF-α,IL-6 in the thrombolysis group were significantly higher than those in the unthrombolysis group (P＜ 0.05),and CRP and WBC count had no significant differences between two groups (P ＞ 0.05).The repatency rate was 79.4％( 104/131 ) in the thrombolysis group,the levels of TNF- α,IL-6 in repatency patients were higher than those in non-repatency patients.There were significant differences(P ＜ 0.05 ).ConclusionsThe thrombolysis is an effective way to cure AMI.The increase of TNF- α,IL-6 after the thrombolysis is considered to be related to reperfusion injury,and CRP,IL-6,TNF-α and WBC count can forecast the inflammation of myocardial necrosis and take an impotant role in predicting the prognosis of the AMI.The antiinflammatory and antioxidation treatment is significant to improve the prognosis of the AMI.

Production and cytotoxicity of the reactive oxygen species induced by diallyl trisulfide in human myeloid leukemia HL-60 cells / 中国病理生理杂志

AIM:To explore the production and cytotoxicity of the reactive oxygen species(ROS)induced by diallyl trisulfide(DATS)in HL-60 cells.METHODS:HL-60 cells were either treated with various doses of DATS alone,or DATS combination with apocynin,a specific NADPH oxidase inhibitor,or with antioxidant N-acetyl-L-cysteine(NAC)for 0,1,3,6,12 and 24 h,respectively.The intracellular ROS level was measured by flow cytometry.The activity of NADPH oxidase was evaluated by NBT reduction experiment.The content of both malondialdehyde(MDA)and the protein carbonyl were analyzed by spectrophotometer.RESULTS:The results from flow cytometry indicated that DATS significantly increased the intracellular ROS level in HL-60 cells(P