Electrochemical Studies of Pirarubicin and Its Interaction with DNA at a Co/GC Ion Implantation Modified Electrode

The electrochemical behavior of pirarubicin(THP) and its interaction with DNA at a Co/GC modified electrode was studied by linear sweep and cyclic voltammetries. In a 0.01 mol/L B-R buffer solution(pH=7.0), the reaction of DNA with THP formed an electrochemical nonactive complex, resulting in a decrease in the THP equilibrium concentration and its reduction current. The composition of the complex was THP∶DNA=2∶1. The combining constant is 2.73×10 10 . The electrode reaction rate constant k s and the electron transfer coefficient α are 1.32 s -1 and 0.56, respectively. The decrease in the peak current was proportional to the DNA concentration and was used to determine the DNA concentration. The experiment of XPS showed that Co was surely implanted into the surface of GCE(glassy carbon electrode) and the implanted Co at GCE can improve the electrocatalytic activity.

Efficacy of transcatheter arterial chemoembolization using pirarubicin-loaded microspheres combined with lobaplatin for primary liver cancer

BACKGROUND Drug-eluting beads show good safety and promising efficacy when used as part of a transarterial chemoembolization regimen for primary liver cancer.However,data on the clinical efficacy and safety of pirarubicin-loaded beads combined with lobaplatin are lacking in China.AIM To evaluate the efficacy and safety of transcatheter arterial chemoembolization using pirarubicin-loaded beads combined with lobaplatin for primary liver cancer.METHODS Between January 2019 and March 2020,60 patients with primary liver cancer were selected at Hebei North University Affiliated First Hospital.According to different treatment methods,the participants were categorized into two groups with 30 patients treated with pirarubicin-loaded microspheres combined with lobaplatin included in an observation group and 30 patients treated with pirarubicin emulsion with lipiodol combined with lobaplatin were included in a control group.The progression-free survival,overall survival,clinical response rate,disease control rate,liver and kidney function and adverse reactions were compared between the two groups.RESULTS The progression-free survival was 14 mo in the observation group,which was significantly higher than 9 mo of the control group(P<0.05).The 6-mo,12-mo and 18-mo survival rates were 93.33%(28/30),66.67%(20/30)and 23.33%(7/30),respectively in the observation group,which were significantly higher than 83.33%(25/30),50.00%(15/30)and 13.33%(4/30),respectively,of the control group(all P<0.05).The clinical efficacy rate and disease control rate were 73.33%and 93.33%,respectively,in the observation group,which were significantly higher than those of the control group(53.55%and 80.00%,respectively,all P<0.05).There was no significant difference in alpha-fetoprotein between the two groups before the treatment(P>0.05).After the treatment,alpha-fetoprotein was 289.06±76.21 ng/m L in the observation group and 365.01±73.11 ng/m L in the control group,which were low in both groups compared with those before the treatment(all P<0.05).The incidence of nausea and vomiting was significantly lower in the observation group than in the control group(P<0.05).There was no significant difference for the adverse reactions of pain and fever between the two groups(P<0.05).CONCLUSION The combination of pirarubicin-loaded beads and lobaplatin can improve treatment efficacy resulting in mild liver function damage and postoperative complications in patients with primary liver cancer.It can be used in clinical practice.

Effects of pirarubicin and mitoxantrone for bladder cancer perfusion chemotherapy on the expression of malignant molecules in serum and lavage fluid

Objective: To study the effects of pirarubicin and mitoxantrone for bladder cancer perfusion chemotherapy on the expression of malignant molecules in serum and lavage fluid. Methods:Patients with advanced bladder cancer who underwent bladder cancer perfusion chemotherapy in our hospital between March 2015 and December 2017 were selected and randomly divided into the THP group who accepted pirarubicin perfusion chemotherapy and the MTZ group who accepted mitoxantrone perfusion chemotherapy. The serum was collected before and after chemotherapy to determine the contents of tumor markers in serum;the lavage liquid was collected after chemotherapy to determine the contents of malignant molecules. Results:Compared with those of same group before chemotherapy, CXCL5, VEGF, CYFRA21-1, DKK1 and DKK3 contents in serum of both group of patients decreased chemotherapy, and CXCL5, VEGF, CYFRA21-1, DKK1 and DKK3 contents in serum of MTZ group after chemotherapy were lower than those of THP group;ILP-2, CyclinD1, Twist, EpCAM and MMP2 contents in lavage liquid of MTZ group were significantly lower than those of THP group whereas Bad, Bax, TRAIL, FasL, E-cadherin and TIMP4 contents were significantly higher than those of THP group. Conclusion: Mitoxantrone for bladder cancer perfusion chemotherapy can be more effectively than pirarubicin to regulate the expression of malignant molecules.

Effect of interleukin-2+pirarubicin infusion chemotherapy combined with systemic chemotherapy on the malignant biological behavior of advanced bladder cancer

Objective: To study the effect of interleukin-2 + pirarubicin infusion chemotherapy combined with systemic chemotherapy on the malignant biological behavior of advanced bladder cancer. Methods: Patients with advanced bladder cancer who were treated in Tongcheng People's Hospital between April 2015 and July 2016 were selected as the research subjects and randomly divided into group A who received interleukin-2 + pirarubicin infusion chemotherapy combined with systemic chemotherapy and the group B who received pirarubicin infusion chemotherapy combined with systemic chemotherapy. The contents of tumor markers and cytokines and the expression of apoptosis molecules in the urine were detected before and after chemotherapy. Results: 8 weeks after chemotherapy, BLCA-1, BLCA-4, CYFRA21-1, TGF-β1, VEGF, EGF, HGF and IGF-2 contents in urine of both groups of patients were significantly lower than those before treatment, Fas, Bad, PTEN and Beclin-1 mRNA expression in urine were significantly higher than those before treatment and BLCA-1, BLCA-4, CYFRA21-1, TGF-β1, VEGF, EGF, HGF and IGF-2 contents in urine of group A were significantly lower than those of group B, Fas, Bad, PTEN and Beclin-1 mRNA expression in urine were significantly higher than those of group B. Conclusion: Interleukin-2+ pirarubicin infusion chemotherapy combined with systemic chemotherapy can be more effective than pirarubicin infusion chemotherapy combined with systemic chemotherapy in inhibiting the malignant biological behavior of advanced bladder cancer.

Mechanism research of pirarubicin postoperative immediately bladder irrigation combined compound matrine injection on treating superficial bladder cancer

Objective:Investigate the mechanism of Pirarubicin postoperative immediately bladder irrigation combined compound matrine injection on treating superficial bladder cancer, thus to provide assistance for clinical therapy of superficial bladder cancer.Methods:A total of 90 cases of patients with superficial bladder cancer treated in our hospital were selected, and randomly divided to be control group and combination group, 45 cases for each. For patients in control group, treatment of Pirarubicin postoperative immediately bladder irrigation was provided after transurethral resection of bladder tumors. For patients in combination group, combined treatment of Pirarubicin postoperative immediately bladder irrigation and compound matrine injection were provided after transurethral resection of bladder tumors. T lymphocyte subsets, cytokines, liver and renal functions of patients in each group were detected before and after treatment.Results: No statistical difference showed on T lymphocyte subsets, cytokines, liver and renal functions between two groups of patients with superficial bladder cancer before and after treatment. Compared with prior treatment, CD8+, cytokines (IFN-γ and IL-2), liver function indexes (AST and ALT) and renal function indexes (BUN and Cre) were significantly increased in two groups of patients after treatment, while T lymphocyte subsets (CD3+, CD4+ and CD4+/CD8+) and cytokines (TNF-α, IL-6 and CRP) were significantly decreased. Differences showed statistical significance. After combined treatment given, T lymphocyte subsets (CD3+, CD4+ and CD4+/CD8+) and cytokines (IFN-γ and IL-2) in combination group were significantly higher than in control group after treatment, cytokines (TNF-α, IL-6 and CRP), CD8+, liver function indexes (AST and ALT) and renal function indexes (BUN and Cre) were significantly lower than in control group after treatment. Differences between the two groups showed statistical significance.Conclusion:Combination of Pirarubicin postoperative immediately bladder irrigation and compound matrine injection could enhance immune functions, improve inflammatory reactions and decrease chemotherapeutics toxicities for patients with superficial bladder cancer. It is of great significance on clinical therapy for those patients.

Evidence-based pharmacoeconomic research of pirarubicin and epirubicin as prophylaxis for recurrence in patients with superficial bladder tumors by bladder instillation after transurethral resection of a bladder tumor

In the present study, we aimed to evaluate the efficiency and cost ofpirarubicin （THP） and epirubicin （EPI） as prophylaxis for recurrence in patients with superficial bladder tumors by bladder instillation after transurethral resection of a bladder tumor （TUR-BT）. Standardized evaluation was performed by analyzing research papers. Moreover, expert opinions, studies and cost data were combined to evaluate cost of THP and EPI. With systematic review and expert opinions, we confirmed that THP and EPI were not statistically different when they were used as prophylaxis for recurrence in patients with superficial bladder tumors by bladder instillation after TUR-BT. Moreover, the cost evaluation of THP and EPI needs to be separately discussed according to original/generic drug. The original drug THP had more cost advantages than EPI, while generic EPI had more cost advantages than THP.

芪参还五胶囊通过抑制心肌坏死性凋亡改善小鼠急性心肌损伤的实验研究

目的观察芪参还五胶囊改善吡柔比星致小鼠急性心肌损伤并探寻其作用机制。方法12周龄雄性C57BL/6小鼠30只,随机分为对照组、模型组及芪参低、中、高剂量组。通过吡柔比星造模,取材前称量体重并通过心脏超声检测左心室结构和功能,ELISA检测血清心肌肌钙蛋白(cTnI)和氨基端前脑钠素(NT-proBNP)含量;HE染色评价小鼠心肌组织形态学改变;RT-qPCR检测心肌组织中焦亡相关基因NOD样受体热蛋白结构域相关蛋白3(NLRP3)、消皮素D(GSDMD)、半胱氨酸天冬氨酸蛋白酶1(Caspase1)和坏死性凋亡相关基因白细胞介素-1α(IL-1α)、白细胞介素-33(IL-33)、肿瘤坏死因子-α(TNF-α)、高迁移率族蛋白B1(HMGB1)的mRNA水平;Weston blotting检测焦亡相关蛋白NLRP3、GSDMD、Cleaved-Caspase1和坏死性凋亡相关蛋白磷酸化混合谱系激酶样蛋白(MLKL)、磷酸化受体相互作用蛋白激酶3(RIP3)、HMGB1水平。结果与对照组相比,模型组小鼠精神状态萎靡,体重下降(P<0.05),射血分数(LVEF)下降(P<0.05),血清c TnI和NT-proBNP水平升高(P<0.05),心肌损伤评分升高(P<0.05),坏死性凋亡相关基因和蛋白水平均有升高(P<0.05);与模型组相比,芪参还五胶囊可以改善小鼠精神状态,增加体重(P<0.05),升高LVEF(P<0.05),降低血清中cTnI和NT-proBNP水平,改善心肌损伤(P<0.05),降低坏死性凋亡相关基因及蛋白表达(P<0.05);5组间焦亡相关基因及蛋白表达无明显差异(P>0.05)。结论芪参还五胶囊可以改善吡柔比星造成的小鼠急性心肌损伤,其机制可能与抑制心肌细胞坏死性凋亡有关。

鸦胆子结合吡柔比星对膀胱癌细胞作用的影响

目的探究鸦胆子结合吡柔比星对膀胱癌细胞的作用。方法选取2023年4—5月期间黑龙江省医院泌尿科1株人BIU-87膀胱癌细胞株为研究对象,细胞培养后,将其接种于96孔板中,以随机数表法分为5组,每组细胞均进行3个平行样本,每个样本细胞均设置5个复孔(每组共计15个样本量),将5组细胞以不同浓度鸦胆子油乳(0、5、10、20、30 mL/L)与吡柔比星(5μmol/L)联合作用,分析不同浓度鸦胆子油乳对膀胱癌细胞增殖抑制作用、细胞凋亡及细胞周期影响,并检测联合用药对核因子κB(Nuclear FactorκB,NF-κB)影响、对细胞中三磷酸腺苷(AdenosineTriphosphate,ATP)结合转运蛋白G家族成员2(ATP-bindingCassette TransporerG2,ABCG2)表达情况影响。结果鸦胆子油乳浓度升高,BIU-87细胞增殖抑制率、坏死率、凋亡率逐渐升高,差异有统计学意义(P均<0.05);鸦胆子油乳浓度为5 mL/L时细胞增殖抑制率、细胞坏死率显著提升,浓度≥10 mL后,细胞凋亡率显著提升,差异有统计学意义(P均<0.05);随鸦胆子油乳浓度升高,BIU-87细胞中S期细胞占比降低,C0/C1期细胞占比升高,差异有统计学意义(P均<0.05);随鸦胆子油乳浓度升高,细胞质中NF-κB表达量逐渐下降,细胞核中NF-κB表达量逐渐升高,细胞膜表面ABCG2表达量下降,差异有统计学意义(P均<0.05)。结论鸦胆子油乳结合吡柔比星,可抑制BIU-87膀胱细胞株增殖,低浓度可促进细胞坏死,高浓度可促进细胞凋亡,并促进NF-κB从细胞质转入细胞核中,抑制ABCG2表达,其效果均存在剂量依赖性。

Efficacy of immediate instillation combined with regular instillations of pirarubicin for Ta and T1 transitional cell bladder cancer after transurethral resection： a prospective, randomized, multicenter study

Background Immediate intravesical instillation of chemotherapeutic agents after transurethral resection （TUR） of non- muscle invasive transitional cell bladder cancer has recently been suggested and has been proven to decrease the tumor recurrence rate significantly. This study is to evaluate the efficacy and safety of immediate intravesical instillation combined with regular instillations of Pirarubicin （THP~） as prophylaxis compared to regular instillations only after TUR operation. Methods This was a prospective, randomized, multi-center, clinical study. Patients diagnosed with non-muscle invasive bladder cancer （Ta and T1） pathologically and suitable for TUR were enrolled randomly into two groups. In the study group, the patients received intravesical instillation within 24-hour post TURBT, followed by regular intravesical therapy using 30 mg/50 ml of THP~ once a week for 8 weeks, and then once a month to 1 year postoperatively Among the patients. In the control group, patients received regular instillation only. Results A total of 403 patients were enrolled into this study from 26 institutions in China. Among the potients, 210 were enrolled into the study group and 193 were enrolled into the control group. At the median follow-up of 18 months, the recurrence rate was 7.8% in the study group, significantly lower than that in the control group （14.3%; P=0.042）. Subgroup analysis showed that the recurrence rate in low and intermediate-risk patients was significantly lower in the study group （6.8%） than in the control group （14.0%; P=0.047）, although no significant differences were found in high-risk patients. Conclusion One immediate dose of THP 30 mg after TURBT followed by regular intravesical therapy appears well tolerated and more effective than regular intravesical therapy for preventing tumor recurrence, especially in low and intermediate-risk patients.

吡柔比星载药微球联合洛铂在原发性肝癌介入栓塞治疗中的临床效果及不良反应分析

目的探究吡柔比星载药微球联合洛铂在原发性肝癌介入栓塞治疗中的临床效果及不良反应。方法选取2020年6月—2022年6月河北北方学院附属第一医院收治的原发性肝癌中晚期患者92例,按随机数字表法分为对照组(n=46)和观察组(n=46)。所有患者均接受介入栓塞治疗,对照组患者给予洛铂灌注治疗,观察组患者在对照组的基础上联合吡柔比星载药微球进行治疗。比较两组患者的疗效,血管内皮生长因子(VEGF)、骨桥蛋白(OPN)、肿瘤坏死因子-α(TNF-α)、总胆红素(TBil)、丙氨酸转氨酶(ALT)水平和不良反应发生情况。结果观察组患者总有效率(84.78%)显著高于对照组(65.22%)(P<0.05);治疗后两组患者VEGF、OPN、TNF-α、TBil、ALT水平均显著低于治疗前,且观察组均显著低于对照组(P<0.05);两组患者不良反应总发生率比较,差异无统计学意义(P>0.05)。结论吡柔比星载药微球联合洛铂在原发性肝癌介入栓塞治疗中的效果较好,可提高疾病控制率,改善患者的肝功能。

血清CEA、CA19-9、β_(2)-MG表达与膀胱癌患者吡柔比星膀胱灌注化疗疗效和生存期相关分析

目的探讨膀胱癌患者血清癌胚抗原(CEA)、癌抗原199(CA19-9)、β_(2)微球蛋白(β_(2)-MG)水平与膀胱癌患者吡柔比星膀胱灌注化疗疗效和生存期的关系。方法选取2021年3月~2023年4月在南阳市第一人民医院接受吡柔比星膀胱灌注化疗的98例膀胱癌患者作为研究对象,根据化疗结果分为化疗有效组(52例)和化疗无效组(46例)。比较两组患者的临床资料和血清CEA、CA19-9、β_(2)-MG水平,并进行单因素和多因素分析、生存分析及Cox回归分析。结果化疗有效组血清CEA、CA19-9、β_(2)-MG水平均低于化疗无效组(P<0.001)。进一步经多因素Logistic回归分析显示血清CEA水平是影响化疗效果和生存期的独立危险因素,高表达者化疗效果差,预后不良。血清CA19-9、β_(2)-MG水平也与化疗效果相关,但不是独立影响因素。结论血清CEA水平是预测膀胱灌注化疗疗效和生存期的重要指标,建议对膀胱癌患者进行血清CEA、CA19-9、β_(2)-MG检测,以指导个体化治疗方案的制定。

经尿道等离子电切术联合吡柔比星膀胱灌注治疗腺性膀胱炎后复发的影响因素及其风险预测

目的探讨经尿道等离子电切术联合吡柔比星膀胱灌注治疗腺性膀胱炎(CG)后复发的影响因素及其风险预测。方法回顾性分析2017年8月-2020年8月联勤保障部队第九八〇医院收治并行经尿道等离子电切术后吡柔比星膀胱灌注化疗的240例CG患者临床资料。分析患者复发情况,比较复发与未复发患者临床资料,采用Logistic多因素回归分析CG复发的危险因素并建立风险模型,绘制受试者工作特征(ROC)曲线评估风险模型的预测效能。结果CG复发34例,复发率为14.17%。复发组患者年龄、RDW、NLR及尿路感染、尿路结石、高危型、肠化生型、弥漫型比例高于未复发组(P<0.05)。临床分型[OR=4.335,95%CI 2.470~7.607]、病理类型[OR=1.709,95%CI 1.059~2.757]、红细胞分布宽度(RDW)[OR=1.799,95%CI 1.173~2.757]、中性粒细胞与淋巴细胞比值(NLR)[OR=1.900,95%CI 1.282~2.818]是CG经尿道等离子电切术联合吡柔比星膀胱灌注化疗后复发的独立危险因素(P<0.05)。风险模型预测CG复发的曲线下面积(AUC)为0.843(95%CI:0.791~0.887),最佳阈值为0.221,敏感度67.5%,特异度87.9%。结论经尿道等离子电切术联合吡柔比星膀胱灌注可减少CG复发,但复发率仍较高,不能使患者显著获益,临床分型、病理类型、RDW、NLR是CG复发的主要危险因素,建立风险模型对CG复发具有一定预测价值。

Dichloroacetate enhances the antitumor effect of pirarubicin via regulating the ROS-JNK signaling pathway in liver cancer cells

Aim:Liver cancer is one of the most common malignancies and has a high recurrence rate.However,current treatment strategies do not achieve satisfactory outcomes in the clinic.To explore a new strategy to enhance the effectiveness of chemotherapy in liver cancer,we investigated whether dichloroacetate(DCA)could enhance the sensitivity of liver cancer cells to pirarubicin(THP).Methods:Liver cancer cells were treated with DCA alone,THP alone,or DCA and THP combined.Cell viability was determined by the CCK-8 assay.Cell apoptosis was analyzed by flow cytometer.Reactive oxygen species(ROS)were detected using a CM-H2DCFDA fluorescence probe.Protein levels were identified by immunoblotting.Results:The results revealed that DCA significantly enhanced the antitumor effect of THP in liver cancer cells.Changes in morphology and adherence ability were observed,as well as decreased cell viability.The results of flow cytometry showed that the combination of THP and DCA significantly increased apoptosis of liver cancer cells.Moreover,compared with THP alone,combination treatment with DCA significantly increased THP-triggered ROS generation in liver cancer cells.The antioxidant N-acetyl-L-cysteine reversed the synergistic effect of DCA and THP on ROS generation,cell viability and apoptosis.Furthermore,phosphorylation of c-Jun N-terminal kinase(JNK)was significantly increased in the DCA and THP combination group.The effects of DCA and THP on cell viability and apoptosis were inhibited by the JNK inhibitor SP600125.Conclusion:The results obtained in the present study indicated that DCA enhanced the antitumor effect of THP in liver cancer cells via regulating the ROS-JNK signaling pathway.

低危非肌层浸润性膀胱癌术后即刻膀胱灌注与维持膀胱灌注的疗效对比

目的分析低危非肌层浸润性膀胱癌(NMIBC)术后患者分别采用即刻膀胱灌注与维持膀胱灌注吡柔比星(THP)的方式进行治疗的效果及不良反应发生情况。方法60例低危NMIBC患者,随机分为观察组和对照组,每组30例。两组患者均接受经尿道膀胱肿瘤电切术(TURBT),观察组患者术后采用即刻灌注,对照组患者术后采用维持灌注。随访至术后1年,比较两组患者血清血管内皮生长因子(VEGF)、成纤维细胞生长因子(FGF)、可溶性细胞间粘附分子-1(sICAM-1)水平及术后复发率、不良反应发生情况。结果术后1年,观察组患者血清VEGF、FGF、sICAM-1水平分别为(32.23±4.12)ng/ml、(14.68±1.34)pg/L、(97.12±8.35)ng/L,对照组患者分别为(31.11±5.42)ng/ml、(13.67±2.46)pg/L、(95.33±12.42)ng/L,比较差异无统计学意义(P>0.05)。观察组患者复发率为13.33%,对照组为10.00%,比较差异无统计学意义(P>0.05)。观察组患者不良反应发生率为6.67%,显著低于对照组的26.67%,差异有统计学意义(P<0.05)。结论低危NMIBC术后即刻膀胱灌注的肿瘤标注物水平、肿瘤复发率与维持膀胱灌注无显著差异,同时不良反应较少,可以减少患者治疗的痛苦和经济负担,具有较高的临床应用价值。

吡柔比星联合地塞米松及沙利度胺治疗多发性骨髓瘤的效果观察

目的:探讨吡柔比星联合地塞米松及沙利度胺治疗多发性骨髓瘤的效果。方法:选取2020年1月-2023年8月郴州市第一人民医院收治的40例多发性骨髓瘤患者作为研究对象,以随机数字表法分为研究组与对照组,各20例。研究组2例失访,2例因更换治疗方案退组;对照组4例失访,2例因更换治疗方案退组;最终研究组纳入16例患者,对照组纳入14例患者。对照组应用地塞米松及沙利度胺治疗,研究组在对照组基础上应用吡柔比星治疗。比较两组血液指标、临床疗效以及不良反应发生情况。结果:治疗前,两组血红蛋白、白蛋白、球蛋白、血小板计数水平比较,差异无统计学意义(P>0.05);治疗后,两组血红蛋白、血小板计数水平均高于治疗前,且研究组高于对照组,两组白蛋白、球蛋白水平均低于治疗前,且研究组低于对照组,差异有统计学意义(P<0.05)。研究组治疗总有效率高于对照组,差异有统计学意义(P=0.011)。两组不良反应总发生率比较,差异无统计学意义(P>0.05)。结论:吡柔比星联合地塞米松及沙利度胺治疗多发性骨髓瘤的效果显著,能够改善患者血液指标,且不会增加不良反应。

HAL光动力治疗联合吡柔比星对膀胱癌细胞的杀伤作用及其机制的体外实验研究

目的探讨六氨基乙酰丙酸(HAL)光动力治疗(PDT)联合吡柔比星(THP)在体外对膀胱癌细胞的协同杀伤作用及可能的机制。方法将膀胱癌细胞株RT4和T24细胞分为空白对照组、PDT组、THP组、PDT+THP组,各组经过相应的处理后,采用CCK-8法检测对细胞增殖的影响,Western blot检测P-gp蛋白的表达,Hoechst/PI双染法检测对细胞凋亡的影响,RT-q PCR检测Bcl-2和Bax基因的表达。结果与单独PDT处理和单独THP处理相比,PDT+THP处理能够显著抑制RT4和T24细胞的增殖能力(均P<0.01),降低癌细胞P-gp蛋白的表达,并增加细胞凋亡能力、下调Bcl-2基因表达(均P<0.01)、上调Bax基因表达(均P<0.01)。结论HAL介导的PDT联合THP对膀胱癌细胞具有协同杀伤作用,其机制可能与联合治疗降低了癌细胞的耐药性、促进癌细胞凋亡有关。

经尿道膀胱肿瘤电切术联合吡柔比星膀胱灌注化疗在浅表性膀胱癌患者中的应用效果

目的探讨经尿道膀胱肿瘤电切术联合吡柔比星膀胱灌注化疗在浅表性膀胱癌患者中的应用效果。方法根据手术方式的不同将90例浅表性膀胱癌分为对照组(n=45)和观察组(n=45),对照组患者采取经尿道膀胱肿瘤电切术治疗,观察组患者采取经尿道膀胱肿瘤电切术联合吡柔比星膀胱灌注化疗。比较两组患者的肿瘤标志物[血管内皮生长因子(VEGF)、成纤维细胞生长因子(FGF)、基质金属蛋白酶9(MMP9)、基质金属蛋白酶2(MMP2)]水平、生活质量[健康调查简表(SF-36)]、并发症发生情况及肿瘤复发情况。结果治疗后1周,两组患者血清VEGF、FGF、MMP9、MMP2水平均低于本组治疗前,且观察组患者血清VEGF、FGF、MMP9、MMP2水平均低于对照组,差异均有统计学意义(P﹤0.05)。治疗后1个月,两组患者SF-36量表各维度评分均高于本组治疗前,且观察组患者SF-36量表各维度评分均高于对照组,差异均有统计学意义(P﹤0.05)。对照组患者的并发症总发生率为8.89%,与观察组患者的6.67%比较,差异无统计学意义(P﹥0.05)。随访6个月,对照组患者的复发率为4.44%,与观察组患者的2.22%比较,差异无统计学意义(P﹥0.05);随访1年,观察组患者的1年复发率为4.44%,低于对照组患者的17.78%,差异有统计学意义(P﹤0.05)。结论经尿道膀胱肿瘤电切术联合吡柔比星膀胱灌注化疗治疗浅表性膀胱癌,能够降低血清因子水平,提高患者生活质量,降低术后复发率,且无明显不良反应。

基于光热效应和pH响应性的聚多巴胺膜靶向纳米粒子的制备及性能评价

目的为构建高效、低毒、高肿瘤靶向性的乳腺癌给药系统,拟采用化疗与光疗相结合的治疗方法对乳腺癌进行治疗。方法本文以盐酸吡柔比星和多西紫杉醇作为模型药物联合使用共同负载于介孔二氧化硅(MSNs)纳米粒内,利用盐酸多巴胺(PDA)碱性条件下自身氧化在介孔二氧化硅表面形成聚多巴胺薄膜,最后通过酰胺化反应将活化后的叶酸修饰于盐酸多巴胺表面,最终制得双载药叶酸修饰聚多巴胺膜包覆的介孔二氧化硅纳米粒(FA-PDA-THP-DTX-MSNs)。结果通过单因素考察最终确定介孔二氧化硅载药条件:载药溶剂为25%乙醇水溶液、药物载体比为1∶1、载药时间为12 h;盐酸多巴胺包覆条件:盐酸多巴胺浓度为0.5 mg·mL^(-1)、搅拌时间为3 h。对双载药叶酸修饰聚多巴胺膜包覆的介孔二氧化硅纳米粒粒径、Zeta电位、傅立叶红外光谱等进行测定并与未进行修饰前介孔二氧化硅的数据进行比较,结果显示盐酸多巴胺和叶酸(FA)均成功修饰。测定最终成型的纳米粒,透射电镜下观察其形态为球形,大小均一,粒度分析仪测定结果显示,平均粒径为(201.4±21.7)nm,PDI指数为0.264,Zeta电位为(+23.3±0.67)mV,盐酸吡柔比星(THP)和多西紫杉醇D(DTX)的载药量分别为(11.77%±0.33%)、(5.72%±0.25%),THP和DTX的包封率分别为(36.92%±0.44%)、(36.02%±0.68%)。双载药叶酸修饰聚多巴胺膜包覆的介孔二氧化硅纳米粒给药系统体外释放实验结果显示双载药叶酸修饰聚多巴胺膜包覆的介孔二氧化硅纳米粒中药物具有良好的缓释性能和酸响应性并且在近红外激光的照射条件下能够实现药物的突释。结论本研究可为聚多巴胺膜包覆双载药光热型纳米粒的抗肿瘤研究提供更加丰富的实验依据,为开发新型纳米粒奠定基础。

微波消解-电感耦合等离子体质谱法测定吡柔比星中10种元素杂质

目的建立电感耦合等离子体质谱(ICP-MS)法测定吡柔比星中Li、V、Co、Ni、Cu、Cd、Hg、As、Sb、Pb共10种元素杂质的含量。方法供试品经微波消解后采用ICP-MS法对10种金属元素进行测定,以Y、Te和Bi元素为内标校正基体效应和漂移。结果10种元素在各自的检测浓度范围内线性关系良好(r均>0.9997)。准确度各浓度点平均回收率为86.3%~115.3%(n=3),加标回收率RSD为0.66%~3.2%(n=3);重复性加标回收率平均值为88.1%~109.8%(n=6),加标回收率RSD为1.0%~2.2%(n=6);中间精密度加标回收率平均值为88.7%~108.5%(n=6),加标回收率RSD为0.69%~1.9%(n=6);两分析人员12份溶液加标回收率RSD为1.3%~5.7%(n=12)。结果均符合现行版的USP中方法学验证的要求,不同样品批次中10种元素杂质的含量均符合ICH规定。结论本方法操作简单,分析速度快,准确性好,灵敏度高,可用于吡柔比星原料药中元素杂质的质量控制。

蛇床子素通过抑制PI3K/Akt/NF-κB信号通路的活化增强吡柔比星对骨肉瘤细胞143B的化疗作用

目的:探讨蛇床子素通过抑制PI3K/Akt/NF-κB信号通路的活化来增强吡柔比星对骨肉瘤细胞的化疗作用。方法:采用MTT法、Transwell实验分别检测蛇床子素、吡柔比星单独和联合对人骨肉瘤细胞143B增殖、迁移和侵袭能力的影响。westernBlotting方法检测PI3K、Akt、NF-κB蛋白表达水平,所有计量资料采用均数±标准差表示,采用SPSS 25.0软件进行统计学分析,各组间差异应用单因素方差分析统计,多组间两两比较采用LSD分析统计,P<0.05为有统计学意义。结果:蛇床子素和吡柔比星联合用药可显著抑制人骨肉瘤143B细胞的增殖、迁移和侵袭能力,显著下调PI3K、Akt、NF-κB蛋白表达水平。结论:蛇床子素可能通过调节PI3K/Akt/NF-κB信号通路来提高吡柔比星对人骨肉瘤143B细胞的杀伤活性。