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排序方式: 共有940条查询结果,搜索用时 641 毫秒
1.
Keiko Goto Yutaka Fujiwara Takeshi Isobe Naoko Chayahara Naomi Kiyota Toru Mukohara Yukari Tsubata Takamasa Hotta Kenji Tamura Noboru Yamamoto Hironobu Minami 《Cancer science》2019,110(6):1987-1994
Although dose reduction of S‐1 is recommended for patients with impaired renal function, dose modification for such patients has not been prospectively evaluated. The aim of the present study was to investigate the pharmacokinetic parameters of 5‐fluorouracil, 5‐chloro‐2,4 dihydroxypyridine and oteracil potassium, and to review the recommended dose modification of S‐1 in patients with renal impairment. We classified patients receiving S‐1 into 4 groups according to their renal function, as measured using the Japanese estimated glomerular filtration rate (eGFR) equation. The daily S‐1 dose was adjusted based on the patient's eGFR and body surface area. Blood samples were collected for pharmacokinetic analysis. A total of 33 patients were enrolled and classified into 4 groups as follows: 10 patients in cohort 1 (eGFR ≥ 80 mL/min/1.73 m2), 10 patients in cohort 2 (eGFR = 50‐79 mL/min/1.73 m2), 10 patients in cohort 3 (eGFR = 30‐49 mL/min/1.73 m2), and 3 patients in cohort 4 (eGFR < 30 mL/min/1.73 m2). Those in cohorts 3 and 4 treated with an adjusted dose of S‐1 showed a similar area under the curve for 5‐fluorouracil (941.9 ± 275.6 and 1043.5 ± 224.8 ng/mL, respectively) compared with cohort 2 (1034.9 ± 414.3 ng/mL). Notably, while there was a statistically significant difference between cohort 1 (689.6 ± 208.8 ng/mL) and 2 (P = 0.0474) treated with an equal dose of S‐1, there was no significant difference observed in the toxicity profiles of the cohorts. In conclusion, dose adjustment of S‐1 in patients with impaired renal function using eGFR is appropriate and safe. 相似文献
2.
Fei Xu Ming‐Liang Ye Yu‐Peng Zhang Wen‐Jie Li Meng‐Ting Li Hai‐Zhou Wang Xiao Qiu Yan Xu Jin‐Wen Yin Qian Hu Wan‐Hui Wei Ying Chang Lan Liu Qiu Zhao 《Cancer science》2020,111(5):1528-1541
Resistance to chemotherapy is a major challenge for the treatment of patients with colorectal cancer (CRC). Previous studies have found that microRNAs (miRNAs) play key roles in drug resistance; however, the role of miRNA‐373‐3p (miR‐375‐3p) in CRC remains unclear. The current study aimed to explore the potential function of miR‐375‐3p in 5‐fluorouracil (5‐FU) resistance. MicroRNA‐375‐3p was found to be widely downregulated in human CRC cell lines and tissues and to promote the sensitivity of CRC cells to 5‐FU by inducing colon cancer cell apoptosis and cycle arrest and by inhibiting cell growth, migration, and invasion in vitro. Thymidylate synthase (TYMS) was found to be a direct target of miR‐375‐3p, and TYMS knockdown exerted similar effects as miR‐375‐3p overexpression on the CRC cellular response to 5‐FU. Lipid‐coated calcium carbonate nanoparticles (NPs) were designed to cotransport 5‐FU and miR‐375‐3p into cells efficiently and rapidly and to release the drugs in a weakly acidic tumor microenvironment. The therapeutic effect of combined miR‐375 + 5‐FU/NPs was significantly higher than that of the individual treatments in mouse s.c. xenografts derived from HCT116 cells. Our results suggest that restoring miR‐375‐3p levels could be a future novel therapeutic strategy to enhance chemosensitivity to 5‐FU. 相似文献
3.
靳培英 《中国新药与临床杂志》1992,(5)
443例(男225例,女218例;年龄36±14a)皮肤病患者,其中150例(扁平疣52例、寻常疣55例、银屑病43例)外用含1.8%十二烷氮(艹卓)酮的1%氟尿嘧啶(5-FU)凝胶作为治疗组,148例外用1%5-FU凝胶及145例外用2.5%5-FU霜作为2个对照组。经双盲对照临床试验,结果表明含1.8%十二烷氮(艹卓)酮的1%5-FU凝胶的疗效明显优于2个对照组(P<0.01及P<0.005)。证明氮(艹卓)酮对5-FU确有渗透促进作用。 相似文献
4.
Optimization of localized 19F magnetic resonance spectroscopy for the detection of fluorinated drugs in the human liver. 总被引:1,自引:0,他引:1
Dennis W J Klomp Hanneke W M Van Laarhoven Arno P M Kentgens Arend Heerschap 《Magnetic resonance in medicine》2003,50(2):303-308
Fluorine MR spectroscopy ((19)F MRS) is an indispensable tool for assessing the pharmacokinetics of fluorinated drugs. Since the metabolism of 5-fluorouracil (5FU), a frequently used cytotoxic drug, is expected to be different in normal liver and in tumor tissue, spatial localization is required for detection by MRS. In this study, three independent signal-to-noise ratio (SNR) optimizations were combined to enable chemical shift imaging (CSI) as a localization method in the detection of 5FU and its metabolites in tumor tissue. First, the hardware was optimized by using circularly polarized coils together with integrated preamplifiers. Second, the optimal pulse angle (Ernst angle) was determined on the basis of T(1) relaxation time measurements of 5FU. Finally, averaging of CSI phase-encoding steps was optimized by using the applied Hamming filter as a weighting function. The combination of these three methods enables the in vivo detection of 5FU and alpha-fluoro-beta-alanine (FBAL) by (19)F MRS, localized in three dimensions in tumor and liver tissue at a time resolution of 4 min at 1.5 Tesla. 相似文献
5.
5-FU纳米微粒的制备及其释药特性研究 总被引:5,自引:1,他引:4
目的 制备一种新型的载氟尿嘧啶(5-FU)纳米微粒并对其体内释药特性进行研究.方法 运用聚合物交联法制备出壳聚糖载氟尿嘧啶纳米粒,通过扫描电镜、激光粒度分析仪对其表征进行检测,紫外分光光度法测定载药量,高效液相色谱法检测体内的释药特性.结果 壳聚糖载氟尿嘧啶纳米粒呈圆形或椭圆形,分散性良好,粒径在120~150nm;载药量为31.000%±0.001%;壳聚糖-5-FU纳米粒注射入兔体内后,初期突释相约在1.5h,峰浓度为5 069.6μg/L,随即进入缓释相,浓度维持在76μg/L,时间长达48h.结论 壳聚糖纳米药物载体可改变5-FU在体内的药代动力学行为,延长其循环时间,具有良好的缓释作用. 相似文献
6.
7.
目的:观察吉西他滨联合顺铂(GP方案)与吉西他滨联合氟尿嘧啶(GF方案)治疗晚期胰腺癌近期疗效和毒副作用的差异。方法:经病理组织学或细胞学证实的60例胰腺癌患者,按照随机对照的原则分为GP组和GF组,各30例。GP组给予吉西他滨1000mg/m~2加生理盐水100ml,静脉滴注30min,第1、8、15天;顺铂40mg,静脉点滴,第15、16、17天。GF组给予吉西他滨1000mg/m~2加生理盐水100ml,静脉滴注30min,第1、8、15天,氟尿嘧啶500mg/m~2加5%葡萄糖液(GS)500ml,静脉点滴6h以上,第1~5天。结果:GP组部分缓解(PR)3例,微效(MR)5例,稳定(NC)12例,进展(PD)5例,PR+MR达32.0%,中位生存期8.7个月,临床受益率(CBR)57.7%,肿瘤标志物CA19-9下降>50%为48.1%。GF组PR3例,MR8例,NC9例,PD4例,PR+MR达45.8%,中位生存期10.1个月,CBR82.1%,CA19-9下降>50%为53.6%。两组经统计学比较,CBR差异有显著性(P<0.05)。主要毒性反应为白细胞减少和血小板减少。结论:吉西他滨联合氟尿嘧啶以及吉西他滨联合顺铂,较以往单药方案疗效高,副作用少,中位生存期长,CBR高;GP方案和GF方案比较,后者的CBR更高。 相似文献
8.
A Sprague-Dawley rat model with DS sarcoma transplanted in the thigh was used to compare transcatheter locoregional i.a. and systemic i.v. administration of 5-fluorouracil (FU) at 12 dose-rate schedules: 25, 50 and 100 mg/kg; bolus, 1, 5 and 24 h infusions. In experiment A tumor (62/67 animals) as well as liver and kidney (56/67 animals) were excised 1 h after a single bolus or 1 h infusion or at the end of 5 and 24 h infusions. (19)F-NMR spectroscopy at 11.7 T was used to quantitate FU and its metabolites in ca. 1 g of tissue at 4 degrees C. In experiment B analogous FU treatments were repeated for 5 days (rats 80+11 controls). Tumor volumes vs time, various blood parameters and survival times were recorded, and a log growth rate parameter log GR, a response index RI, and a toxicity index TI were calculated. The i.a. vs i.v. ratios for tumor concentrations of FU and total anabolites (F-Nucl) were >1 for nearly all treatments and increased with infusion time at the higher doses. F-Nucl in tumor correlated linearly with total fluorine concentration (Tot. F range 30-1100 nmol/g) over all treatments (r=0.92, slope=0.45, p<0.0001). For non-bolus i.v. treatments [FU+F-Nucl] decreased linearly with decreasing FU dose rate (r(2)=0.74, zero intercept), while i.a. treatments showed non-linear behavior. For non-bolus treatments the mean log GR per treatment group showed a negative correlation (r=-0.87) with log[F-Nucl]. The most effective non-toxic treatments were 25 mg/kg over 5 or 24 h; the i.a. route was superior to i.v. on the basis of [FU+F-Nucl], RI, the reduction in log GR, and Kaplan-Meier survival statistics. For liver and kidney Tot. F (>83% FU catabolites) reached ca. 3-4 and 6-7 micromol/g, respectively, at the highest dose rates for either route; F-Nucl were detected only for Tot. F>500 nmol/g and increased exponentially as Tot. F increased (toxic treatments). The concentrations of the main catabolite (alpha-fluoro-beta-alanine, FBAL) in tumor did not correlate with Tot. F but rather with FBAL levels in kidney (r=0.90, all treatments), indicating that uptake of liver-derived FBAL from the circulation is the major source of FBAL in tumor. 相似文献
9.
R. Metz M. Delgado R. Keiling P. Cappelaere J. P. Armand G. Prevot J. L. Misset J. Grimbert G. Mathe 《Investigational new drugs》1985,3(2):163-166
Summary In our wide experience of treating advanced breast carcinoma with chemotherapy, the combination of doxorubicin (DOX), vincristine (VCR), cyclophosphamide (CPM) and fluorouracil (FU) gave a complete plus partial response rate of over 60%, with 100% alopecia and frequent cardiac toxicity depending on total dose.After the EORTC Clinical Screening Group phase II trial we have conducted an expected difference method comparative phase II trial using the combination DOX, VCR, CPM, FU and the combination of MTX (10mg/m2), VCR, CPM and FU on a population of 50 breast carcinoma patients similar to those taking part in the first study.The reasons for similarity of action will be presented and discussed. 相似文献
10.
目的探讨应用电化学疗法治疗中晚期食管癌和贲门癌的临床疗效。方法电化学疗法治疗中晚期食管癌和贲门癌42例,对其治疗前后的疗效进行比较。结果通过对比电化学治疗前后食管X线钡餐检查及进食改善情况显示,88%的患者在接受电化学治疗后进食明显改善,89%的患者食管狭窄扩大在0.5cm以上。结论电化学疗法治疗食管癌和贲门癌解除食管梗阻见效快,疗效显著,能恢复患者饮食,可为实施其他治疗创造条件,使其远期生存率提高。 相似文献