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Multicenter Analysis of mFOLFOX6 with oxaliplatin Stop-and-Go Strategy Using Oral Uracil-Tegafur with Leucovorin for Unresectable Colorectal Cancer in Elderly Patients

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Journal of Cancer Therapy 2014年第2期5卷 147-154页

作者： Tetsu Yamamoto Kuniyuki Katano Shinichi Sugimoto Akiyoshi Kanazawa Eiji Hira Hiroshi Takeda Yoshitoshi Sato Yutaka Yamashiro Yoshitsugu Tajima Masahide Ikeguchi Department of Digestive and General Surgery Faculty of Medicine Shimane University Izumo Japan Department of Gastroenterological Surgery Matsue Red Cross Hospital Matsue Japan Department of Gastroenterological Surgery Osaka Red Cross Hospital Osaka Japan Department of Gastroenterological Surgery Tottori Red Cross Hospital Tottori Japan Department of Surgery Saihaku Hospital Saihaku Japan Department of Surgery Shimane Prefectural Central Hospital Izumo Japan Division of Surgical Oncology Faculty of Medicine Tottori University Yonago Japan

Background: This study evaluated the tolerability and efficacy of intermittent oxaliplatin treatment based on mFOLFOX6 using oral uracil-tegafur(UFT) and leucovorin(LV) maintenance therapy in the treatment of elderly patients with advanced colorectal cancer. Methods: Ten non-elderly patients (70 years) with advanced/recurrent colorectal cancer were enrolled in this prospective, multicenter cooperative group clinical trial. The mFOLFOX6 regimen was administered for eight cycles with maintenance therapy with oral UFT/LV treatment until progression. In cases with disease progression, mFOLFOX6 was reintroduced. Results: Grade 2 peripheral neuropathy was noted in 30.0% and 25.0% of the elderly and non-elderly patients, respectively. The observed time to treatment failure (TTF) was 6.3 months in the elderly patients and 6.4 months in the non-elderly patients. The disease control rate was 83.3% in each group. Conclusion: Our new stop-and-go strategy using oral UFT/LV is well-tolerated and effective even in elderly patients.

关键词： Colorectal Cancer oxaliplatin Uracil-Tegafur (UFT) Leucovorin Elderly Patient Stop-and-Go

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Efficacy of 5-FU or oxaliplatin Monotherapy over Combination Therapy in Colorectal Cancer

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Journal of Cancer Therapy 2015年第4期6卷 345-355页

作者： Maria Toloudi Panagiotis Apostolou Ioannis Papasotiriou Research Genetic Cancer Centre Ltd. (R.G.C.C. Ltd.) Florina Greece

Recent clinical and research development supports the use of 5-fluorouracil in combination with oxaliplatin for the treatment of patients with advanced colorectal cancer (CRC). 5-Fluorouracil (5-FU), which is as an anti-metabolite, is a widely used cytostatic drug. Although the rate of response, quality of life and overall survival differs between CRC patients, the above combination remains a widely used chemotherapeutic regimen. In some cases, a cancer stem cell (CSC) population may resist the majority of chemotherapeutic models. This study investigated if monotherapy is more efficacious than 5-fluorouracil and oxaliplatin combined for the treatment of CRC, using a CRC cell line and a CSC-like line. Cell viability was evaluated by cellular-based assays, and quantitative polymerase chain reaction (q-PCR) assays were performed to assess the expression of specific genes (TYMS,?DNMT1,?NANOG, DHFR, SHMT1, ERCC1, DPYD) correlated with 5-FU and oxaliplatin resistance. We observed that 5-fluorouracil was more effective in both CRC and CSCs. This finding proved the hypothesis that, in some cases, monotherapy may be more successful in CRC treatment than a drug combination that may be cytotoxic and inflict adverse side effects.

关键词： 5-Fluorouracil oxaliplatin FOLFOX Colon Cancer Stem Cells

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Different effects of gemcitabine + paclitaxel and gemcitabine +oxaliplatin chemotherapy on the malignant biology of advanced bladder cancer

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Journal of Hainan Medical University 2017年第21期23卷 114-117页

作者： Jun Zhao Jia-En Xie Department of Urology the People's Hospital of Kaizhou District in ChongqingChongqing405400

Objective: To explore the different effects of gemcitabine + paclitaxel and gemcitabine +oxaliplatin chemotherapy on the malignant biology of advanced bladder cancer. Methods: A total of 109 patients with advanced bladder cancer who were treated in the hospital between June 2014 and January 2017 were retrospectively analyzed and then divided into paclitaxel group (n=52) and oxaliplatin group (n=57). Paclitaxel group received gemcitabine + paclitaxel therapy, and oxaliplatin group received gemcitabine + oxaliplatin therapy. The differences in the expression of proliferation, invasion and autophagy genes in the urine were compared between the two groups before and after treatment. Results: Before treatment, there was no statistically significant difference in the expression of proliferation, invasion and autophagy genes in the urine between the two groups. After treatment, proliferation genes ABCE1 and YAP mRNA expression in the urine of paclitaxel group were lower than those of oxaliplatin group while MTSS1 mRNA expression was higher than that of oxaliplatin group;invasion genes CBX7 and NDRG2 mRNA expression were higher than those of oxaliplatin group while ILK, KPNA2 and SPOCK1 mRNA expression were lower than those of oxaliplatin group;autophagy gene LC3 mRNA expression was lower than that of oxaliplatin group while Beclin1 mRNA expression was higher than that of oxaliplatin group. Conclusion: Gemcitabine +paclitaxel chemotherapy may be more effective in inhibiting the malignant biological behavior of tumor cells in patients with advanced bladder cancer.

关键词： Advanced bladder cancer Paclitaxel oxaliplatin Malignant biological

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Intervention for oxaliplatin-induced hypersensitivity in China:a cross-sectional internet-based survey

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Oncology and Translational Medicine 2020年第6期6卷 277-281页

作者： Min Li Wei Li Yue Wang Xiaofang Shangguan Rui Huang Dong Liu Chengliang Zhang Department of Pharmacy Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030China Statistical Department Tongji Hospital Affiliated with Tongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030China School of Pharmacy Tongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030China

Objective This cross-sectional study aimed at investigating the intervention status and the influence of oncologists on oxaliplatin-induced hypersensitivity reactions(OIHR).Methods Snowball sampling was used to send questionnaires to oncologists in various provinces and cities in China,via the internet,to collect data on their socio-demographic characteristics,the occurrence of OIHR,and the current status of interventions.One-way ANOVA and T-test of geographic samples were used to explore the relationship between the incidence of OIHR and intervention measures.Results A total of 401 valid questionnaires were collected,most respondents were 30–40 years old,and most oncologists had 5 years of working experience.The proportions of glucocorticoid and H1 receptor antagonist use for OIHR prevention were 67.83%and 38.65%,respectively.The proportion of oncologists with longer working years and higher professional titles who used glucocorticoids for OIHR prevention was higher,and the observed OIHR incidence was lower.Pretreatment with glucocorticoids may be an effective preventive measure and can reduce the incidence of the OXA allergic reactions(P<0.05).Conclusion The risk awareness of junior oncologists to OIHR prevention should be strengthened,and clinical efficacy evaluation of glucocorticoids in OIHR prevention should be further promoted.

关键词： oxaliplatin hypersensitivity reactions intervention cross-sectional survey

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Effect Observation of Clinical Treatment with oxaliplatin and Tiggio for Biliary Tract Tumors on Advanced Stage

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Journal of Clinical and Nursing Research 2021年第3期5卷 66-68页

作者： Wei Zheng Haibin Wang Jiao Zhou Shaanxi Provincial People's Hospital Xi’an 710068Shaanxi ProvinceChina

Objective:To investigate the effect of oxaliplatin combined with tiggio in the treatment of advanced biliary tract tumors.Methods:The research period was from November 2019 to November 2020.80 patients with advanced biliary tumor disease were enrolled.They were divided into groups according to the order of admission,with 40 cases in each group.The control group received oxaliplatin combined with gemcitabine,and the experimental group received oxaliplatin combined with tiggio.Incidence of adverse reactions,time to disease progression,survival time and clinical efficacy were checked and assessed.Results:Compared with the incidence of adverse reaction of the experimental group,which was 5.00%(2/40),the incidence of adverse reaction of the control group was 25.00%(10/40).The chi-square value=6.2745,p-value=0.0122.The time to progression and survival time of patients in the experimental group were shorter than those of the control group,with significant differences between the groups(poxaliplatin and Tiggio in the treatment of advanced biliary tract tumors has higher safety and reduces the incidence of adverse reactions.

关键词： Advanced stage Biliary tumors oxaliplatin Tiggio

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Clinical Efficacy and Safety of oxaliplatin-tegafur,Gimeracil and Oteracil Potassium and Vinorelbine-Pt in the Treatment of Advanced Triple Negative Breast Cancer

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Advances in Modern Oncology Research 2019年第5期5卷 21-24页

作者： Miroslav Samaržija Lela Bitar US Food and Drug Administration Center for Biologics Evaluation and ResearchOffice of Biostatistics and EpidemiologySilver SpringMD Memorial Sloan Kettering Cancer Center New YorkNY

The purpose of this study was to investigate the efficacy and safety of oxaliplatin combined with tegafur,gimeracil and oteracil potassium(SOX regimen)and vinorelbine combined with Pt(NP regimen)in the treatment of advanced triple negative breast cancer(TNBC).First of all,88 patients with advanced breast cancer were selected and divided into observation group and control group with 44 cases each by random number method.Both groups received conventional supportive therapy.On this basis,SOX regimen was adopted in the observation group and NP regimen in the control group,and the efficacy,occurrence of toxic and side effects in the two groups were compared.The results showed that the objective effective rates and clinical benefit rates of the two groups were statistically significant(P<0.05).In addition,both groups had hand foot syndrome,diarrhea,liver function damage,decreased platelet(PLT)and other toxic side effects,but the incidence of rash,oral ulcer and pigmentation in the observation group was significantly lower than that in the control group(P<0.05).Therefore,both SOX regimen and NP regimen can effectively treat advanced TNBC adverse reactions,but SOX regimen was more effective.

关键词： oxaliplatin Tegafur,gimeracil and oteracil potassium Vinorelbine Pt

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Primavist<sup>TM</sup>in the Diagnosis of oxaliplatin Induced Sinusoidal Obstruction: a Case Report

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Journal of Cancer Therapy 2011年第3期2卷 381-383页

作者： Mansoor Ali Khan Tony Blakeborough Nick Tiffin Ahmed Al-Mukhtar 不详

This is a case report of a patient who underwent oxaliplatin based neo-adjuvant chemotherapy for colorectal liver metastases, and subsequently developed sinusoidal obstruction, which was detected by Primavist enhanced... 详细信息

关键词： oxaliplatin Sinusoidal Obstruction Liver Injury

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A pre-column derivatization-HPLC method for determination of oxaliplatin(L-OHP)content and entrapment efficiency in nanoparticles

A pre-column derivatization-HPLC method for determination of...

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第二届亚洲药物制剂科学与技术研讨会-第二届《亚洲药物制...

作者： Xiaodan Zhou,Li Yang~*,Shu Wang,Xiaojiao Tang,Qi Zhai Department of pharmaceutics,Shenyang Pharmaceutical University,Shenyang 110016,PR China

Purpose:To develop an improved -HPLC method for the determination of oxaliplatin(L-OHP) content and entrapment efficiency in nanoparticles.Methods:After derivatization with sodium diethyldithiocarbamate(DDTC),Pt(DDTC) and diazepam(the internal standard) was separated on C18 column (250 mm×4.6 mm,5μm) at 30℃using a mobile phase consisting of methol and water(75:25,v/v) at flow rate of 1 ml·min;The method was validated with respect to selectivity,linearity,precision and accuracy,limit of quantification and stability.The ultrafiltration was employed to separate the free L-OHP from nanoparticles to calculate the entrapment efficiency.Results:The calibration curve of L-OHP was linear in the concentration range of 5.26-31.53 ug·ml.(r=0.9997) with the limit of quantification(LOQ) of 0.42 ug/mL.The variation coefficients were not more than 1.63%.The mean recoveries was from 98.29%to 100.45%.The content and the encapsulation efficiency of L-OHP nanoparticles were 1.69mg/ml and 63%,respectively.Conclusion:The present method can be used to determine L-OHP content in prepared nanoparticles.as well as entrapment efficiency.

关键词： oxaliplatin Pre-column derivatization HPLC Nanoparticles Entrapment efficiency

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Saracatinib联合oxaliplatin对人肝癌细胞株MHCC97L的作用及其耐药相关机制研究

Saracatinib联合Oxaliplatin对人肝癌细胞株MHCC97L的作用及其耐...

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作者：任雪娇延安大学

学位级别：硕士

背景:我国作为慢性肝炎及肝硬化大国,原发性肝癌发病率居世界首位,每年发病率及病死率均占全球一半以上。目前原发性肝癌是我国第4位常见恶性肿瘤及第2位肿瘤致死病因。手术是肝癌最主要、最有效的治疗方法,其次有肝动脉化疗栓塞术(Tran... 详细信息

背景:我国作为慢性肝炎及肝硬化大国,原发性肝癌发病率居世界首位,每年发病率及病死率均占全球一半以上。目前原发性肝癌是我国第4位常见恶性肿瘤及第2位肿瘤致死病因。手术是肝癌最主要、最有效的治疗方法,其次有肝动脉化疗栓塞术(Transarterial chemoembolization,TACE)、局部射频消融、放疗、系统治疗(化疗及靶向治疗)、中医药治疗、免疫治疗等。但由于原发性肝癌具有隐匿性及高侵袭性的特点,大部分患者在发现时已是中晚期,失去了接受手术治疗的机会。有效的系统治疗可以减轻肿瘤负荷,改善症状,延长生存。常用的一线系统治疗为靶向治疗,首选索拉菲尼(证据等级1)。临床常首选一种系统治疗方式,耐药或进展后更换为另一种系统治疗方式,如首选靶向治疗,可更换为包含奥沙利铂(oxaliplatin)的FOLFOX化疗,但是oxaliplatin在肝癌患者中应用时易产生原发性及继发性耐药。有研究发现,通过Saracatinib与细胞毒药物或其他抗癌药物联合使用可改善肝细胞癌预后。因此本研究尝试探索Saracatinib与oxaliplatin联合或序贯应用对肝癌细胞的作用及其相应机制。目的:1、明确Saracatinib联合及序贯oxaliplatin在肝癌治疗中的效果;2、探索Saracatinib和oxaliplatin治疗肝癌的最佳组合方式;3、研究Saracatinib联合或序贯oxaliplatin治疗肝癌以及化疗耐药机制。方法:1、选择人肝癌细胞株MHCC97L细胞株作为实验细胞,通过CCK8检测细胞增殖初步验证Saracatinib及其他分子靶向药联合oxaliplatin作用于MHCC97L细胞株的疗效,并通过CCK8检测细胞增殖活性,绘制细胞增殖曲线图形式再次验证联合的疗效;2、设计Saracatinib与oxaliplatin互相序贯化疗方案,体外构建Saracatinib耐药的肝癌细胞株MHCC97L-Src,oxaliplatin耐药的肝癌细胞株MHCC97LOxa,通过CCK8测细胞增殖比较IC50值说明MHCC97L-Src耐药细胞株对oxaliplatin的耐药性改变,MHCC97L-Oxa耐药细胞株对Saracatinib的耐药性改变;3、对耐药相关基因进行确定:通过前期比较分析野生型MHCC97L细胞株及MHCC97L-Src细胞株基因表达谱,野生型MHCC97L细胞株及MHCC97LOxa细胞株基因表达谱,找到共同表达的基因,并通过KEGG通路分析两种细胞系中共同改变的基因,再把我们需要验证的差异性基因进行基因相对表达量的检测,在两耐药细胞株中表达倍数均最高的基因作为耐药相关基因进行后续试验。4、Western Blot验证MHCC97L细胞株及MHCC97L-Src细胞株中此耐药蛋白的表达,通过小干扰RNA沉默MHCC97L细胞株及MHCC97L-Src细胞株中耐药蛋白的表达后,再次通过CCK8检测其对oxaliplatin敏感性的改变。5、采用SPSS 25.0软件、Graphad prism 7.0软件进行数据分析,两组间计量数据比较采用双侧Student’S t检验法,以评价平均值差异的统计学显著性。实验至少进行3次,poxaliplatin与抗癌分子靶向药物(包括PI3K、MAPK通路等中29种抑制剂,包括Src抑制剂Saracatinib)联合用药的疗效,发现oxaliplatin与Saracatinib联合使用产生了拮抗作用;2、MHCC97L-Src耐药细胞株对oxaliplatin的化疗敏感性明显减弱(108.71±11.24μmol/L vs.20.85±4.86μmol/L;p=0.0092);MHCC97L-Oxa细胞株对Saracatinib的化疗敏感性明显增强(1.23±0.31μmol/L vs.4.30±0.97μmol/L;p=0.0141),两组间差异均有统计学意义(poxaliplatin化疗耐药性均降低(25.59±5.82μmol/L vs.8.41±2.09μmol/L;p=0.0085)及(40.43±8.12μmol/L vs.103.71±8.74μmol/L;p=0.0008),两组间差异均有统计学意义(poxaliplatin联合Saracatinib处理沉默ABCG1基因的MHCC97L细胞株(MHCC97Ls

关键词： Saracatinib oxaliplatin 原发性肝癌 ABCG1

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A pilot phase Ⅱ study of neoadjuvant triplet chemotherapy regimen in patients with locally advanced resectable colon cancer

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Chinese Journal of Cancer Research 2016年第6期28卷 598-605页

作者： Haitao Zhou Yan Song Jun Jiang Haitao Niu Hong Zhao Jianwei Liang Hao Su Zheng Wang Zhixiang Zhou Jing Huang Department of Colorectal Surgery National Cancer Center/Cancer HospitalChinese Academy of Medical Science&Peking Union Medical CollegeBeijing 100021China Department of Medical Oncology National Cancer Center/Cancer HospitalChinese Academy of Medical Science&Peking Union Medical CollegeBeijing 100021China Department of Imageology National Cancer Center/Cancer HospitalChinese Academy of Medical Science&Peking Union Medical CollegeBeijing 100021China Department of Abdominal Surgery National Cancer Center/Cancer HospitalChinese Academy of Medical Science&Peking Union Medical CollegeBeijing 100021China

Objective： This study aims to investigate the feasibility, safety and efficacy of triplet regimen of neoadjuvant chemotherapy in patients with locally advanced resectable colon cancer.Methods： Patients with clinical stage IIIb colon cancer received a perioperative triple chemotherapy regimen（oxaliplatin 85 mg/m2 and irinotecan 150 mg/m2, combined with folinic acid 200 mg, 5-fluorouracil 500 mg bolus and then 2,400 mg/m2 by 44 h infusion or capecitabine 1 g/m2 or S-1 40–60 mg b.i.d orally d 1–10, repeated at 2-week intervals） for 4 cycles. Complete mesocolic excision was scheduled 2–6 weeks after completion of neoadjuvant treatment and followed by a further 6 cycles of FOLFOXIRI or XELOX. Primary outcome measures of this stage II trial were feasibility, safety, tolerance and efficacy of neoadjuvant treatment.Results： All 23 patients received neoadjuvant chemotherapy and underwent surgery. Twenty-one patients（91.3%） had reductions in tumor volume after neoadjuvant treatment, and 13 patients（56.5%） had grade 3–4toxicity. No patients had severe complications from surgery. Preoperative therapy resulted in significant downstaging of T-stage and N-stage compared with the baseline clinical stage including one pathological complete response.Conclusions： Neoadjuvant triple chemotherapy has high activity and acceptable toxicity and perioperative morbidity, and is feasible, tolerable and effective for locally advanced resectable colon cancer.

关键词： 5-Fluorouracil colon cancer irinotecan oxaliplatin neoadjuvant chemotherapy

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