cisplatin

摘要： BACKGROUND Ovarian cancer is one of the three most common malignant tumors of the female reproductive tract and ranks first in terms of mortality among gynecological tumors.Epithelial ovarian carcinoma(EOC)is the most common ovarian malignancy,accounting for 90%of all primary ovarian tumors.The clinical value of cytoreductive surgery in patients with platinum-resistant recurrent EOC remains largely unclear.AIM To evaluate the feasibility of secondary cytoreductive surgery for treating platinum-resistant recurrent EOC.METHODS This was a retrospective study of the clinical data of patients with platinumresistant EOC admitted to the Cancer Hospital of the University of Chinese Academy of Sciences between September 2012 and June 2018.Patient baseline data were obtained from clinical records.Routine follow-up of disease progression was performed as follows.CA125 assessment and physical examination were performed every 3 wk during treatment,including gynecological examination.Imaging assessment was carried out every 12 wk by B-mode ultrasound,computed tomography,or magnetic resonance imaging.The primary outcome was progression-free survival(PFS).Secondary outcomes included overall survival(OS),chemotherapy-free interval(CFI),and complications.Follow-up ended on April 15,2019.RESULTS A total of 38 patients were included.R0 resection was achieved in 25(65.8%) patients and R1/2 in 13 (34.2%). Twenty-five (65.8%) patients required organ resection. Nine(23.7%) patients had operative complications, 36 (94.7%) received chemotherapy, and five (13.2%)had targeted therapy. Median PFS and OS were 10 (95%CI: 8.27-11.73) months and 28 (95%CI:12.75-43.25) months, respectively;median CFI was 9 (95%CI: 8.06-9.94) months. R0 resection andpostoperative chemotherapy significantly prolonged PFS and OS (all P < 0.05), and R0 resectionalso significantly prolonged CFI (P < 0.05). Grade ≥ 3 complications were observed, includingrectovaginal fistula (n = 1), intestinal and urinary fistulas (n = 1), and renal failure-associated death(n = 1). Except for the patient who died after surgery, all other patients with complications weresuccessfully managed. Two patients developed intestinal obstruction and showed improvementafter conservative treatment.CONCLUSIONSecondary cytoreductive surgery is feasible for treating platinum-resistant recurrent EOC. Thesefindings provide important references for the selection of clinical therapeutic regimens.

摘要： Objective:To systematically evaluate the efficacy and safety of rh-endostain(YH-16,Endostar)combined with vinorelbine and cisplatin(NP regimen)in the treatment of non-small cell lung cancer(NSCLC),and to provide evidence-based reference for clinical drug use.Methods:Retrieved from PubMed,EMBASE,the Cochrane Library,Clinical Trials,CNKI,VIP and Wan Fang database,randomized controlled trials(RCT)about YH-16 combined with NP regimen(NPY regimen,trial group)vs.NP regimen(control group)for NSCLC were collected.After screening the literature and extracting the data,the two persons evaluated the quality of the included studies,and used Rev Man 5.3 software to merge effect size.Results:A total of 18 articles were included,with a total of 2051 patients.Results of Meta-analysis showed that response rate[RR=1.66,95%CI(1.44,1.91),P0.05).Conclusion:Compared with NP regimen alone,NPY regimen can improve the efficacy and quality of life of NSCLC patients,reduce the level of tumor markers,and does not increase the occurrence of adverse reactions,and has good efficacy and safety.However,the existing evidence shows that NPY regimen has the same effect as NP regimen alone in improving the 1-year survival rate of patients.The above conclusions need to be confirmed by further studies.

摘要： BACKGROUND The targeted therapy cetuximab[directed at the epidermal growth factor receptor(EGFR)]in combination with 5-fluorouracil and platinum-based chemotherapy(the EXTREME regimen)has shown substantial efficacy for patients with recurrent or metastatic squamous cell carcinoma of the head and neck(R/M SCCHN).Thus,this scheme has been established as the preferred first-line option for these patients.However,more recently,a new strategy combining platinum,taxanes,and cetuximab(the TPEx regimen)has demonstrated similar efficacy with a more favorable toxicity profile in clinical trials.AIM To evaluate the safety and efficacy of the TPEx scheme as first-line therapy in advanced SCCHN in a multicenter cohort study.METHODS This retrospective multicenter cohort study included patients with histologically confirmed recurrent or metastatic SCCHN treated with first-line TPEx at five medical centers in Argentina between January 1,2017 and April 31,2020.Chemotherapy consisted of four cycles of docetaxel,cisplatin,and cetuximab followed by cetuximab maintenance therapy.Clinical outcomes and toxicity profiles were collected from medical charts.Treatment response was assessed by the investigator in accordance with Response Evaluation Criteria in Solid Tumors(version 1.1).Adverse events were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events(version 4.0).RESULTS Twenty-four patients were included.The median age at diagnosis was 58 years(range:36-77 years).The majority of patients(83.3%)received at least four chemotherapy cycles in the initial phase.In the included group,the overall response rate was 62.5%,and 3 patients achieved a complete response(12.5%).The median time to response was 2.4 mo[95% confidence interval(CI):1.3-3.5].With a median follow-up of 12.7 mo(95%CI:8.8-16.6),the median progression-free survival(PFS)was 6.9 mo(95%CI:6.5-7.3),and the overall survival rate at 12 mo was 82.4%.Patients with documented tumor response showed a better PFS than those with disease stabilization or progression[8.5 mo(95%CI:5.5-11.5)and 4.5 mo(95%CI:2.5-6.6),respectively;P=0.042].Regarding the safety analysis,two-thirds of patients reported at least one treatment-related adverse event,and 25% presented grade 3 toxicities.Of note,no patient experienced grade 4 adverse events.CONCLUSION TPEx was an adequately tolerated regimen in our population,with low incidence of grade 3-4 adverse events.The median PFS were consistent with those in recent reports of clinical trials evaluating this treatment combination.This regimen may be considered an attractive therapeutic strategy due to its simplified administration,decreased total number of chemotherapy cycles,and treatment tolerability.

摘要： Objective:T-LAK-cell-originated protein kinase(TOPK),a PSD95-Disc large-ZO1(PDZ)binding kinase(PBK),is a novel member of the mitogen-activated protein kinase(MAPK)family.Studies have shown that TOPK plays a critical role in the function of tumor cells,including apoptosis and mitosis.However,little is known on the effect of TOPK in cisplatin-induced acute kidney injury(CP-AKI).This study aimed to investigate the role and mechanism of TOPK in CPAKI.Methods:Cisplatin was administered to C57BL/6 mice and cultured kidney tubular epithelial cells(TECs)to establish the CP-AKI murine or cellular models.TECs were then stimulated with the specific inhibitor of TOPK OTS514 or transfected with the recombinant-activated plasmid TOPK-T9E to inhibit or activate TOPK.The TECs were treated with AKT inhibitorⅧfollowing stimulation with OTS514 or cisplatin.Western blotting and flow cytometry were used to evaluate the cell cycle and apoptosis of TECs.Results:The analysis revealed that the TOPK activity was significantly suppressed by cisplatin,both in vivo and in vitro.Furthermore,the pharmacological inhibition of TOPK by OTS514,a specific inhibitor of TOPK,exacerbated the cisplatin-induced cell cycle arrest in the G2/M phase and apoptosis of cultured TECs.Moreover,the TOPK activation via the TOPK-T9E plasmid transfection could partially reverse the cell cycle arrest at the G2/M phase and apoptosis of cisplatin-treated TECs.In addition,AKT/protein kinase B(PKB),as a TOPK target protein,was inhibited by cisplatin in cultured TECs.The pharmaceutical inhibition of AKT further aggravated the apoptosis of TECs induced by cisplatin or TOPK inhibition.TOPK systematically mediated the apoptosis via the AKT pathway in the CP-AKI cell model.Conclusion:These results indicate that TOPK activation protects against CP-AKI by ameliorating the G2/M cell cycle arrest and cell apoptosis.

摘要： BACKGROUND Testicular germ cell tumor(TGCT)is the most curable solid tumor and most common cancer among men 18-39 years.While cisplatin-based chemotherapy has significantly lengthened the survival of patients with TGCT,it is associated with a high rate of thromboembolic events(TEE).AIM To summarize our single-center experience highlighting patients who were diagnosed with TGCT and received platinum-based chemotherapy,with special attention to those patients who suffered a TEE.METHODS A retrospective analysis of the medical records and imaging studies of 68 consecutive individuals who were diagnosed with TGCT and received platinumbased chemotherapy at our Institution in a metropolitan community between January 1,2014 and December 31,2019.RESULTS A total of 19(28%)patients experienced a TEE following orchiectomy which occurred during chemotherapy in 13(68%)of these patients.Patients with a higher pathologic stage(stage III)were significantly(P=0.023)more likely to experience a TEE compared to patients who had a lower stage.Additionally,patients who were treated with 3 cycles of bleomycine,etoposide,and cisplatin and 1 cycle of etoposide and cisplatin or 4 cycles of etoposide and cisplatin were significantly 5(P=0.02)times more likely to experience a TEE compared to patients who were treated withonly 3 cycles of bleomycine,etoposide,and cisplatin.CONCLUSION Due to numerous factors that predispose to a TEE such as large retroperitoneal disease,higher clinical stage,greater number of chemotherapy cycle,central venous catheter,cigarette smoking,and possible cannabis use,high-risk ambulatory patients with TGCT treated with cisplatin-based chemotherapy may benefit from prophylactic anticoagulation.Randomized studies to evaluate the safety and efficacy of prophylactic anticoagulants are warranted in this young patient population generally devoid of medical co-morbidities.

摘要： Many cancer cells in solid tumors are hypoxic or pseudohypoxic and create acidic environment for malignancy progression. Under low oxygen conditions (hypoxia), hypoxia-inducible factors (HIFs) play pathological roles in cancer cell survival and spreading. HIF regulates several genes such as genes of glucose transporters that enhance anaerobic glycolysis, angiogenesis, erythropoiesis and carbonic anhydrase IX (CA-IX). CA-IX is a cell-surface glycoprotein that catalyzes the hydration of CO2 to protons and bicarbonate ions (respiratory acidification). This process is involved in adaptation to acidosis and implicated in cancer progression. Therefore, CA-IX inhibitors (such as sulfonamide-based compounds) showed hoping results in reduction malignancy progression. The article aims to reversal the malignant hypoxic environment in solid tumors to create a condition of weakness within the cancer for further focused cisplatin potency. This article suggests the use of modified synthesized HIF as a drug delivery molecule for both carbonic anhydrase IX inhibitor and glycosylated cisplatin that damages the DNA of malignant cell. HIF molecule has high affinity to bind with CA IX-expressing malignant cells, which is followed by cell entrance via endocytosis. Once the HIF-Cisplatin-CA-inhibitor complex enters the cell, the carbonic anhydrase inhibitor will improve the cellular pH that makes the environment unsuitable for HIF 1α function and it may be ubiquitinated. So, the raise in target genes transcription will be arrested. On the other hand, once the synthetized HIF is degraded, the cisplatin molecules will be released inside the malignant cell and start to damage its DNA. This approach may be a good solution for many solid tumors.

摘要： Chemotherapy is widely used for non-small cell lung cancer(NSCLC)patients at a late stage;however,NSCLC patients often acquire resistance to chemotherapeutic drugs,thus limiting the therapy efficacy.Melittin,a major component of bee venom,possesses anti-tumor activity in various cancer cells.Here,we examined the effects of melittin on A549/DDP cisplatin-resistant lung adenocarcinoma cells and xenografts formed from this cell line and investigated the possible target of melittin.Treatment with melittin resulted in the induction of cell apoptosis,glycolysis inhibition,and reduction of phosphorylated AKT(p-AKT)in A549/DDP cells.We also identified that tripartite motif-containing 8(TRIM8)was a potential target of melittin.Moreover,we found that TRIM8 mRNA expression was elevated in NSCLC specimens as compared to adjacent normal tissues(N=25)and that patients with high expression of TRIM8 had a poor prognosis for lung adenocarcinoma.The knockdown of TRIM8 had a similar effect of melittin,while overexpression of TRIM8 reversed the effects of melittin in A549/DDP cells.More importantly,we revealed that melittin enhanced cisplatin sensitivity in A549/DDP cells and tumor growth in vivo using a xenograft model of A549/DDP cells.In conclusion,melittin appears to be a potential chemotherapy sensitization agent in NSCLC.

摘要： Carrier-free drug self-delivery systems consisting of amphiphilic drug-drug conjugate(ADDC)with well-defined structure and nanoscale features have drawn much attention in tumor drug delivery.Herein,we report a simple and effective strategy to prepare ADDC using derivatives of cisplatin(CP)and dasatinib(DAS),which further selfassembled to form reduction-responsive nanoparticles(CP-DDA NPs).DAS was modified with succinic anhydride and then connected with CP derivative by ester bonds.The size,micromorphology and in vitro drug release of CP-DDA NPs were characterized.The biocompatibility and bioactivity of these carrier-free nanoparticles were then investigated by HepG2 cells and H22-tumor bearing mice.In vitro and in vivo experiments proved that CPDDA NPs had excellent anti-tumor activity and significantly reduced toxicities.This study provides a new strategy to design the carrier-free nanomedicine composed of CP and DAS for synergistic tumor treatment.

摘要： Objective:To analyze and study the efficacy and safety of Endu combined with pemetrexed and cisplatin in the clinical treatment of lung adenocarcinoma.Methods:From August 2016 to September 2020,32 patients with lung adenocarcinoma who were treated in our hospital were selected for group trials.According to their specific treatment plan,the patients were divided into control group and experimental group,with 16 cases in each group.The control group was treated with pemetrexed and cisplatin,and the experimental group was treated with Endostar combined with the treatment received by the control group.The clinical efficacy and safety of the two regimens were assessed by comparing the changes in symptoms and the incidence of adverse reactions between the two groups of patients after treatment.Results:The disease control rate of the experimental group was significantly higher than that of the control group,and there was no significant difference in the incidence of adverse reactions between the two groups.Conclusions:From the experimental results,we found that the treatment of patients with lung adenocarcinoma by Endostar combined with pemetrexed and cisplatin can effectively improve the treatment efficacy without increasing adverse reactions and therefore relevant chemotherapy regimens can be considered for wider clinical applications.

摘要： Objective:This paper mainly study on the effects of irinotecan/cisplatin and etoposide/cisplatin regimens in the treatment of small cell lung cancer.Methods:50 cases of small cell lung cancer patients in our hospital were divided into control group and experimental group and administered with etoposide/cisplatin and irinotecan/cisplatin regimen,and the treatment effects of the two regimens were compared statistically.Results:After treatment,both groups achieved high treatment efficiency,and the incidence of toxic side effects was low,with no significant difference(P>0.05);serological ABCG2 and FGFBP1 level indicators were better than the control group,both showing significant differences(P<0.05).Conclusions:Irinotecan has achieved better improvement in serological indicators in the first-line treatment of small cell lung cancer,with no significant difference in short-term treatment efficiency.