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.

Pilot study of intravesical instillation of two new generation anthracycline antibiotics in prevention of superficial bladder cancer recurrence

Background Superficial bladder cancer accounts for 60%-70% of all bladder cancer cases in China, when treatment consists of only transurethral resection of the bladder tumor （TUR-BT）, recurrence and progresses in the bladder are observed in some patients. There are numerous reports of trials of intravesical instillation of anticancer agents with the objective of lowering this recurrence rate. The aim of this study was to compare the prophylactic efficacy and safety of epirubicin （EPI）, pirarubicin （THP） and hydroxycamptothecin （HCPT） in superficial bladder cancer.Methods This study enrolled a total of 189 patients who had been diagnosed with superficial bladder cancer during the period from 2004 through 2007 at Beijing Friendship Hospital. All patients were randomly allocated to one of three treatment groups. Patients in group A received 29 doses of EPI 30 mg/30 ml, patients in group B received 29 doses of THP 30 mg/30 ml, and patients in group C received 29 doses of HCPT 30 mg/30 ml, over a period of 24 months.Results The recurrence-free rate in the 2 anthracycline treatment groups （A and B） were significantly better than that of the HCPT treatment group. In the safety evaluation, the incidences of pollakiuria, pain on urination, dysuria, hematuria,and contracted bladder were not significantly different between groups A and B, but some were significantly higher in groups A and B than that in group C.Conclusion The efficacy of EPI and THP was significantly better than HCPT in the prevention of bladder cancer recurrence.

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.

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.