检索结果-南通市图书馆

CMAB009 plus irinotecan versus irinotecan-only as second-line treatment after fluoropyrimidine and oxaliplatin failure in KRAS wild-type metastatic colorectal cancer patients:promising findings from a prospective,open-label,randomized,phase III trial

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

Cancer Communications 2019年第1期39卷 258-270页

作者： Yuankai Shi Jin Li Jianming Xu Yan Sun Liwei Wang Ying Cheng Wei Liu Guoping Sun Yigui Chen Li Bai Yiping Zhang Xiaohui He Yi Luo Zhehai Wang Yunpeng Liu Qiang Yao Yuhong Li Shukui Qin Xiaohua Hu Feng Bi Rongsheng Zheng Xuenong Ouyang Department of Medical Oncology Beijing Key Laboratory of Clinical Study On Anticancer Molecular Targeted DrugsNational Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021P.R.China Fudan University Shanghai Cancer Center Shanghai 200032P.R.China The Affiliated Hospital of Military Medical Sciences Beijing 100071P.R.China Shanghai General Hospital Shanghai 200080P.R.China Jilin Cancer Hospital Changchun 130012JilinP.R.China Tumor Hospital of Hebei Province Shijiazhuang 050011HebeiP.R.China The First Affiliated Hospital of Anhui Medical University Hefei 230022AnhuiP.R.China Fujian Provincial Cancer Hospital Fuzhou 350014FujianP.R.China Chinese People’s Liberation Army General Hospital Beijing 100853P.R.China Zhejiang Cancer Hospital Hangzhou 310022ZhejiangP.R.China Hunan Cancer Hospital Changsha 410013HunanP.R.China Shandong Cancer Hospital Jinan 250117ShandongP.R.China The First Hospital of China Medical University Shenyang 110001LiaoningP.R.China Tianjin People’s Hospital Tianjin 300121P.R.China Sun Yat-sen University Cancer Center State Key Laboratory of Oncology in South ChinaCollaborative Innovation Center of Cancer MedicineGuangzhou 510060GuangdongP.R.China Chinese People’s Liberation Army Bayi Hospital Nanjing 210002JiangsuP.R.China The Guangxi Zhuang Autonomous Region Tumor Hospital Nanning 530021GuangxiP.R.China West China Hospital Chengdu 610041SichuanP.R.China First Affiliated Hospital of Bengbu Medical College Bengbu 233004AnhuiP.R.China Fuzhou People’s Liberation Army General Hospital Fuzhou 350025FujianP.R.China

Background:The 5-fluorouracil/leucovorin plus oxaliplatin(FOLFOX)regimen is the standard first-line treatment for metastatic colorectal cancer(mCRC),however,the optimal second-line regimen for KRAS wild-type mCRC patients is still *** this study,we aimed to determine the clinical efficacy and safety of CMAB009 plus irinotecan compared to irinotecan-only as a second-line regimen for treating KRAS wild-type mCRC ***:Patients with KRAS wild-type mCRC who had previously failed to respond to FOLFOX treatment were ran-domly assigned in a 2:1 ratio,to receive CMAB009 plus irinotecan or *** receiving irinotecan-only were permitted to switch to CMAB009 therapy on disease progression and were grouped as the sequential-CMAB009 *** primary endpoints were overall response rate(ORR)and median progression-free survival(PFS).The second-ary endpoints were median overall survival(OS),disease control rate(DCR),clinical benefit rate(CBR),and duration of response(DOR).Results:The CMAB009 plus irinotecan arm demonstrated significantly improved ORR(33.2%vs.12.8%;P<0.001)and longer median PFS(169 days vs.95 days;P<0.001)as compared to the irinotecan-only *** receiv-ing CMAB009 plus irinotecan also demonstrated improved DCR(80.1%vs.65.2%,P<0.001),CBR(30.0%vs.14.6%,P<0.001),and DOR(210 days vs.109 days;P<0.001)as compared to ***,patients treated with CMAB009 had an increased risk of skin rash(66.9%vs.5.5%,P<0.001)and paronychia(9.8%vs.0.0%,P<0.001).Anti-drug antibodies(ADA)were detected in 3.6%of patients,and only 0.9%of patients who received CMAB009 experienced hypersensitivity *** patients receiving sequential-CMAB009 therapy after failure with irinotecan,their median PFS was 84 days (95% CI 65 to 113 days). The median OS was 425 days for patients receiving CMAB009 plus irinotecan and 401 days for those with sequential-CMAB009 (P = 0.940). Conclusions: Treatment with CMAB009 plus irinotecan was found

关键词： CMAB009 Cetuximab Irinotecan Second-line mCRC EGFR KRAS Immunogenicity fluoropyrimidine Oxaliplatin failure

The efficacy of *** adjuvant chemotherapy on biliary tract cancer after R0 resection

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

Chinese Journal of Cancer 2017年第5期36卷 222-230页

作者： Young Saing Kim Chi-Young Jeong Haa-Na Song Tae Hyo Kim Hong Jun Kim Young-Joon Lee Soon Chan Hong Division of Hematology and Oncology Department of Internal MedicineGachon University Gil Medical Center Incheon 405.706 South Korea Department of Surgery Institute of Health Sciences Gyeongsang National University Hospital Gyeongsang National University School of Medicine 79 Gangnam-roJinju 660.702 South Korea Department of Internal Medicine Institute of Health Sciences Gyeongsang National University Hospital Gyeongsang National University School of Medicine Jinju 660.702 South Korea.

Background: The optimal treatment strategy for biliary tract cancer(BTC) after curative?intent resection remains con?troversial. The purpose of this study was to evaluate the efficacy of fluoropyrimidine?based adjuvant chemotherapy for BTC patients undergoing microscopically margin?negative(R0) ***: We retrospectively analyzed the clinical data of BTC patients who underwent curative?intent R0 resection. Patients were eligible if they received either fluoropyrimidine?based adjuvant chemotherapy or observation after R0 ***: A total of 153 patients were included. In the entire patient cohort, no significant differences were observed in 5?year overall survival(OS) rates(48.4% vs. 39.6%, P = 0.439) or 3?year recurrence?free survival(RFS) rates(49.1% vs. 39.5%, P = 0.299) between patients who received fluoropyrimidine?based adjuvant chemotherapy or observation. However, for patients with stages Ⅱ and Ⅲ BTC, chemotherapy significantly improved 5?year OS rate(52.4% vs. 35.6%, P = 0.002) and 3?year RFS rate(55.5% vs. 39.1%, P = 0.021) compared with ***: fluoropyrimidine?based adjuvant chemotherapy may prolong the survival of patients with stages Ⅱ and Ⅲ BTC after R0 resection.

关键词： Biliary tract cancer Adjuvant chemotherapy fluoropyrimidine R0 resection Prognosis

DNA damage-mediated cellular senescence promotes hand-foot syndrome that can be relieved by thymidine prodrug

维普期刊数据库

同方期刊数据库评论

在线全文

学校读者我要写书评

暂无评论

Genes & Diseases 2023年第6期10卷 2557-2571页

作者： Bingxue Yang Xinran Xie Zhaoyu Wu Dazhao Lv Jiajun Hu Yuyun Chen Jiaxing Li Shuyue Luo Jiacheng Li Jie Luo Shiyi Zhang School of Pharmacy Shanghai Jiao Tong UniversityShanghai 200240China School of Pharmacy and School of Biomedical Engineering Shanghai Jiao Tong UniversityShanghai 200240China

Hand-foot syndrome(HFS)is a widely recognized dose-limiting cutaneous toxicity effect of fluoropyrimidine chemotherapy agents that impairs clinical benefits and treatment *** though the cause and pathophysiology of HFS are relatively widely reported,how the toxicity of fluoropyrimidine translates into persistent inflammation has not been ***,prevention and treatment strategies for HFS based on its mechanistic occurrence and development are *** our study,we demonstrated that cGAS-STING signaling pathway-mediated cellular senescence played a critical role in the inflammatory reaction and provided a therapeutic solution for ***,DNA damage,as the primary cytotoxic cause,in keratinocytes induces cell cycle arrest,activates the cGAS-STING signaling pathway,and subsequently mediates cellular senescence,ultimately fueling a robust secondary inflammatory response that results in *** importantly,the thymidine prodrug thymidine diacetate was proven to be effective in preventing HFS by compensating for thymidylate deficiency to facilitate the replication and repair of DNA and thus causing the escape from cellular *** data highlight the importance of DNA damage-mediated cellular senescence in the etiology of HFS and provide a potential therapeutic anchor point for fluoropyrimidine-induced HFS.

关键词： Cellular senescence cGAS-STING Cutaneous toxicity DNA damage fluoropyrimidine Hand-foot syndrome Keratinocytes Thymidine prodrug

Retrospective analysis of adjuvant chemotherapy for curatively resected gastric cancer

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

World Journal of Gastroenterology 2014年第12期20卷 3356-3363页

作者： Wei Deng Qi-Wei Wang Xiao-Tian Zhang Ming Lu Jie Li Yan Li Ji-Fang Gong Jun Zhou Zhi-Hao Lu Lin Shen Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education) Department of Gastrointestinal OncologyPeking University Cancer Hospital and Institute

AIM: To determine the efficacy of adjuvant chemotherapy for gastric cancer in clinical practice, a retrospective analysis was conducted in a high-volume Chinese cancer center.

关键词： Adjuvant chemotherapy Gastric cancer Lymphadenectomy fluoropyrimidine Platinum

Review of 5-FU resistance mechanisms in colorectal cancer:clinical significance of attenuated on-target effects

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

Cancer Drug Resistance 2023年第2期6卷 257-272页

作者： William H.Gmeiner Charles Chidi Okechukwu Department of Cancer Biology and Comprehensive Cancer Center Wake Forest University School of MedicineWinston-SalemNC 27157USA Integrative Physiology and Pharmacology Graduate Program InstitutionWake Forest University School of MedicineWinston-SalemNC 27157USA

The emergence of chemoresistant disease during chemotherapy with 5-Fluorouracil-based(5-FU-based)regimens is an important factor in the mortality of metastatic CRC(mCRC).The causes of 5-FU resistance are multifactorial,and besides DNA mismatch repair deficiency(MMR-D),there are no widely accepted criteria for determining which CRC patients are not likely to be responsive to 5-FU-based ***,there is a need to systematically understand the mechanistic basis for 5-FU treatment failure and an urgent need to develop new approaches for circumventing the major causes of 5-FU *** this manuscript,we review mechanisms of 5-FU resistance with an emphasis on:(1)altered anabolic metabolism limiting the formation of the primary active metabolite Fluorodeoxyuridylate(5-Fluoro-2'-deoxyuridine-5'-O-monophosphate;FdUMP);(2)elevated expression or activity of the primary enzymatic target thymidylate synthase(TS);and(3)dysregulated programmed cell death as important causes of 5-FU ***,these causes of 5-FU resistance can potentially be overcome through the use of next-generation fluoropyrimidine(FP)polymers(e.g.,CF10)that display reduced dependence on anabolic metabolism and more potent TS inhibitory activity.

关键词： fluoropyrimidine 5-FU resistance colorectal cancer chemotherapy precision medicine thymidylate synthase

Improved potency of F10 relative to 5-fluorouracil in colorectal cancer cells with p53 mutations

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

Cancer Drug Resistance 2018年第1期1卷 48-58页

作者： Anthony Dominijanni William H.Gmeiner Department of Cancer Biology Wake Forest School of MedicineWinston-SalemNC 27157USA

Aim:Resistance to fluoropyrimidine drugs(FPs)is a major cause of mortality in colorectal cancer(CRC).We assessed the potency advantage of the polymeric FP F10 relative to 5-fluorouracil(5-FU)in four human CRC cell lines that differ only in TP53 mutational status to determine how p53 mutations affect drug response and whether F10 is likely to improve ***:HCT-116 human CRC cells(p53^(+/+))and three isogenic variants(p53^(-/-),R248W/+,R248W/-)were assessed for drug *** factors were derived from cell viability data and used to establish the relative potency advantage for *** studies with exogenous uridine/thymidine determined if cytotoxicity resulted from DNA-directed ***:Significant resistance to 5-FU resulted from p53-loss or from gain-of-function(GOF)mutation(R248W)and was greatest when GOF mutation was coupled with loss of wild-type p53.F10 is much more potent than 5-FU(137-314-fold depending on TP53 mutational status).F10 and 5-FU induce apoptosis by DNA-and RNA-directed mechanisms,respectively,and only F10 shows a modest enhancement in cytotoxicity upon co-treatment with ***:TP53 mutational status affects inherent sensitivity to FPs,with p53 GOF mutations most deleterious.F10 is much more effective than 5-FU regardless of TP53 mutations and has potential to be effective to CRC that is resistant to 5-FU due,in part,to TP53 mutations.

关键词： fluoropyrimidine colorectal cancer p53 drug resistance

Entrapment of DNA topoisomerase-DNA complexes by nucleotide/nucleoside analogs

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

Cancer Drug Resistance 2019年第4期2卷 994-1001页

作者： William H.Gmeiner Department of Cancer Biology Wake Forest School of MedicineWinston-SalemNC 27157USA

Topoisomerases are well-validated targets for cancer chemotherapy and DNA topoisomerase 1(Top1)is the sole target of the camptothecin(CPT)class of anticancer *** the last 20 years,multiple studies have shown Top1 activity is modulated by non-native DNA structures and this can lead to trapping of Top1 cleavage complexes(Top1cc)and conversion to DNA double strand *** the perturbations to DNA structure that generate Top1cc are nucleoside analogs that are incorporated into genomic DNA during replication including cytarabine,gemcitabine,and 5-fluoro-2’-deoxyuridine(FdU).We review the literature summarizing the role of Top1cc in mediating the DNA damaging and cytotoxic activities of nucleoside *** also summarize studies demonstrating distinct differences between Top1cc induced by nucleoside analogs and CPTs,particularly with regard to DNA ***,these studies demonstrate that,while Top1 is a common target for both Top1 poisons such as CPT and nucleoside analogs such as FdU,these agents are not *** recent years,studies have shown that Top1 poisons and nucleoside analogs together with other anti-cancer drugs such as cisplatin cause replication stress and the DNA repair pathways that modulate the cytotoxic activities of these compounds are being *** present an overview of this evolving literature,which has implications for how targeting of Top1 with nucleoside analogs can be used more effectively for cancer treatment.

关键词： DNA topoisomerase 1 cancer chemotherapy cytarabine gemcitabine fluoropyrimidine

Synthesis and Antimicrobial Studies of New Trifluoromethylpyrimidine Analogues

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

Journal of Pharmacy and Pharmacology 2015年第1期3卷 9-19页

作者： Shaikha Saif Al-Neyadi Alaa Eldin Salem Ibrahim Mahmoud Abdou Department of Chemistry University of United Arab Emirates Abu Dhabi AI-Ain 15551 United Arab Emirates

This paper describes the synthesis of a new series of trifluoromethylpyrimidine and their potential antimicrobial evaluation. We have prepared 10 novel pyrimidine derivatives in high yields and short reaction time using microwave irradiation. Compounds 4a,b and 6a,b showed good antimicrobial activity against Gram-positive bacteria; Clostridium perfringens, Bacillus pumilus and Enterococcusfaecalis. These compounds were found to be the most potent antimicrobials compared to ampicillin, tetracycline, and streptomycin that showed no activity against Enterococcusfaecalis. Compounds 4a,b and 6a,b exhibited great antimicrobial potency against all tested bacteria strains at a MIC of 3.125-100 μg/mL whereas only 4a showed the antimicrobial activity against Gram-negative bacteria Klebsiella pneumonia with a MIC value 12.5 pg/mL.

关键词： Synthesis microwave fluoropyrimidine antimicrobial.

Rationale and Study Protocol of the J-SAVER Study: A Phase II Study of S-1 on Alternate Days Combined with Bevacizumab in Patients Aged ≥75 Years with Metastatic Colorectal Cancer

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

Journal of Cancer Therapy 2017年第11期8卷 1040-1048页

作者： Toshikazu Moriwaki Tetsuya Eto Akihito Tsuji Nobushige Kakinoki Mitsuo Shimada Takashi Maeba Hiroaki Hatano Ikuo Takahashi Hiroyasu Ishida Kazuho Ikeda Yoshiaki Bando Ichinosuke Hyodo Division of Gastroenterology Faculty of Medicine University of Tsukuba Tsukuba Japan Department of Gastroenterology Tsuchiura Kyodo General Hospital Tsuchiura Japan Department of Medical Oncology Kobe City Medical Center General Hospital Kobe Japan Department of Gastroenterology Hitachi General Hospital Hitachi Japan Department of Surgery Tokushima University Tokushima Japan Department of Surgery Japan Community Health Care Organization Ritsurin Hospital Takamatsu Japan Department of Surgery Matsuyama Shimin Hospital Matsuyam Japan Department of Surgery Matsuyama Red Cross Hospital Matsuyama Japan Department of Gastroenterology National Hospital Organization Mito Medical Center Higashi Ibaraki-Gun Japan Department of Gastroenterology Koyama Memorial Hospital Kashima Japan Department of Surgery Tokushima Prefecture Naruto Hospital Naruto Japan

fluoropyrimidine combined with bevacizumab is commonly used in elderly patients with metastatic colorectal cancer worldwide. However, the proportion of elderly patients who discontinued treatment due to toxicities was higher than that of younger patients. The aim of this study is to develop a less toxic schedule of S-1, while maintaining the anti-tumor effect. This phase II study is aimed to evaluate an alternate-day administration of S-1 combined with bevacizumab in untreated elderly patients (aged ≥75 years) with metastatic colorectal cancer. The primary endpoint is progression-free survival, and the secondary endpoints are safety, response rate, and overall survival. The expected median progression-free survival is 8.5 months, and the minimum efficacy threshold is 5.0 months. The total required sample size is calculated as 50 patients, with a 2-sided type I error of 0.10 and a power of more than 80%. This study is ongoing, and fifty-four patients were enrolled until October 2016. We hope that S-1 on alternate days combined with bevacizumab for elderly patients with colorectal cancer is well tolerated and can maintain effectiveness. Trial registration: UMIN clinical trials UMIN000010402.

关键词： Alternate Days Bevacizumab Colorectal Cancer fluoropyrimidine Elderly Older S-1