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31.
目的 探讨汉黄芩素(wogonin)联合氟尿嘧啶(5-FU)对人肝癌细胞Hep-G2生长活性的影响。 方法 实验分汉黄芩素组、5-FU组、汉黄芩素+5-FU组和空白对照组,采用MTT法观察药物对肿瘤细胞体外生长活性的影响,采用流式细胞仪分析肿瘤细胞凋亡率的变化。 结果 MTT实验结果显示汉黄芩素(5、10、20、40 μmol/L)作用24、48 h后对肿瘤细胞具有一定的增殖抑制作用(P<0.05);5-FU(5、10、20、40 mg/L)作用24、48 h后对肿瘤细胞增殖有明显的抑制作用(P<0.05);与单用组对肿瘤细胞的抑制作用相比,汉黄芩素联合5-FU组的抗肿瘤作用呈相互拮抗作用(P<0.05);汉黄芩素联合5-FU给药48 h后,联合指数CI值呈现剂量依赖性,CI值随汉黄芩素浓度的加大而增大,说明随汉黄芩素浓度的加大,其拮抗5-FU抗肿瘤效应的作用也越来越明显(P<0.05)。 结论 汉黄芩素具有一定的抗肿瘤作用,但可拮抗5-FU的抗肿瘤作用,具体机制有待进一步研究。 相似文献
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目的观察评价肝动脉化疗栓塞(TACE)联合灌注奥沙利铂(OXA)、氟尿嘧啶(5-Fu)及吡柔比星(THP)方案治疗原发性肝癌的疗效和安全性。方法回顾分析采用TACE术中动脉灌注OXA/5-Fu/THP化疗药物治疗的原发性肝癌患者65例,及同期行单纯肝动脉栓塞(TAE)治疗的原发性肝癌患者21例,分为TACE组和TAE组。对TACE灌注OXA/5-Fu/THP的疗效、不良反应发生率、无进展生存时间(PFS)及总生存期(OS)进行综合评价,并与单纯肝动脉栓塞进行对比分析研究。结果 TACE联合OXA/5-Fu/THP治疗的65例患者中,客观缓解率(ORR)55.4%,疾病控制率(DCR)81.5%;患者的中位PFS时间为11.5个月,中位OS时间为18.5个月;单因素分析中,Child-Pugh A级、无门脉癌栓、无肿瘤转移、肿瘤直径小及TACE治疗次数多的患者预后较好,差异有统计学意义(P<0.05);巴塞罗那分期(BCLC)B期的患者预后优于C期的患者,差异有统计学意义(P=0.000);Cox多因素分析中门脉癌栓及肿瘤远处转移是患者预后的独立危险因素。与单纯TAE 相比,TACE 联合OXA/5-Fu/THP 可提高患者的mPFS。结论TACE术中动脉灌注OXA/5-Fu/THP治疗原发性肝癌的疗效较好,不良反应少。 相似文献
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Assessment of 5‐fluorouracil and 4‐nitroquinoline‐1‐oxide in vivo genotoxicity with Pig‐a mutation and micronucleus endpoints 下载免费PDF全文
Changhui Zhou Min Zhang Pengcheng Huang Honggang Tu Zheng Wang Stephen D. Dertinger Dorothea K. Torous Yan Chang 《Environmental and molecular mutagenesis》2014,55(9):735-740
Genotoxicity assessments were conducted on male Sprague Dawley rats treated with 5‐fluorouracil (5‐FU) and 4‐nitroquinoline‐1–oxide (4NQO) as part of an international validation trial of the Pig‐a mutant phenotype assay. Rats were orally exposed to 0, 11.5, 23, or 46 mg/kg/day 5‐FU for three consecutive days (Days 1–3); blood was sampled on Days ?1, 4, 15, 29, and 45. Pig‐a mutant phenotype reticulocyte (RETCD59?) and mutant phenotype erythrocyte (RBCCD59?) frequencies were determined on Days ?1, 15, 29, and 45, and percent micronucleated reticulocytes (%MN‐RET) were measured on Day 4. Rats were treated with 4NQO for 28 consecutive days by oral gavage, at doses of 1.5, 3, or 6 mg/kg/day. RBCCD59? and RETCD59? frequencies were determined on Days ?1, 15, and 29, and MN‐RET were quantified on Day 29. Whereas 5‐FU was found to increase %MN‐RET, no significant increases were observed for RBCCD59? or RETCD59? at any of the time points studied. The high dose of 4NQO (6 mg/kg/day) was observed to markedly increase RBCCD59? and RETCD59? frequencies, and this same dose level caused a weak but significantly elevated increase in MN‐RET (approximately twofold). Collectively, the results provide additional support for the combination of Pig‐a mutation and MN‐RET into acute and 28‐day repeat‐dose studies. Environ. Mol. Mutagen. 55:735–740, 2014. © 2014 Wiley Periodicals, Inc. 相似文献
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Heiko Rühl Lars Schröder Jens Müller Rolf Fimmers Shorena Sukhitashvili Julia Welz Walther C. Kuhn Johannes Oldenburg Christian Rudlowski Bernd Pötzsch 《Thrombosis research》2014
Introduction
The estrogen antagonist tamoxifen (TAM) increases the thrombotic risk similar to estrogen containing oral contraceptives (OC). In OC users this risk is attributed to alterations of hemostasis resulting in acquired resistance to activated protein C (APC). TAM-induced APC resistance has not been reported yet.Materials and Methods
Blood samples were collected prospectively from women with breast cancer before (n = 25) and monthly after start of adjuvant TAM treatment (n = 75). APC resistance was evaluated on basis of the effect of APC on the endogenous thrombin generation potential. To detect increased in vivo APC generation APC plasma levels were measured using a highly sensitive oligonucleotide-based enzyme capture assay. Routine hemostasis parameters were measured additionally.Results
APC sensitivity decreased by 41% (p = 0.001) compared to baseline after one month of TAM application and remained significantly decreased during the study period. Free protein S increased (p = 0.008) while other analyzed procoagulant factors, inhibitors, and activation markers of coagulation decreased or did not change significantly. In five patients the APC concentration increased to non-physiological levels but an overall significant increase of APC was not observed.Conclusions
This is the first study showing acquired APC resistance under TAM therapy. Acquired APC resistance might explain the increased thrombotic risk during TAM treatment. Observed changes of hemostasis parameters suggest different determinants of TAM-induced APC resistance than in OC-induced APC resistance. The presence of acquired APC resistance in TAM patients warrants further evaluation if these patients may benefit from antithrombotic prophylaxis in the presence of additional thrombotic risk factors. 相似文献36.
J.‐P. Feng X.‐L. Yuan M. Li J. Fang T. Xie Y. Zhou Y.‐M. Zhu M. Luo M. Lin D.‐W. Ye 《Colorectal disease》2013,15(1):27-33
Aim The aim of the study was to analyse the prevalence and characteristics of secondary diabetes induced by 5‐fluorouracil (5‐FU) based chemotherapy in non‐diabetic patients with colorectal cancer (CRC). Method A total of 422 consecutive CRC patients who received 5‐FU‐based chemotherapy were retrospectively analysed. Fasting plasma glucose (FPG) levels were determined before each cycle of chemotherapy during active treatment and regular follow‐up. The prevalence and characteristics of secondary hyperglycaemia were investigated, with special focus on the clinical outcome. Results Among the 422 CRC patients, 60 had pre‐existing hyperglycaemia. In the remaining 362 with normal FPG levels before chemotherapy, 42 (11.6%) and 41 (11.3%) patients developed diabetes and impaired fasting glucose during the study period. Among the 42 secondary diabetic patients, 22 (52.4%) received anti‐diabetes drug therapy, in 7 (16.7%) cases the FPG level returned to normal without any active intervention, and 13 (30.9%) cases received diet control and physiotherapy. Thirty‐one (8.6%) patients developed diabetes. Based on the Common Terminology Criteria for Adverse Events, an adverse event over Grade 3 occurred in seven cases during follow‐up. Diabetes‐related adverse events had a serious negative impact on chemotherapy in six cases. Diabetes‐related death occurred in three patients. Conclusions Secondary diabetes associated with 5‐FU‐based chemotherapy occurs in around 10% of CRC patients, with a significant negative impact on treatment and clinical outcome. 5‐FU‐related diabetes should be regarded as a common side effect of 5‐FU treatment. 相似文献
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目的观察三联疗法治疗转移性大肠癌的临床效果、毒性反应以及患者依从性。方法选择2012年4月至2013年8月就诊的转移性大肠癌患者120例,随机分为A组B组,各60例。A组采用改良的FOLFOX7方案,第1天予奥沙利铂(L-OHP)130 mg/m2+5%葡萄糖注射液500 m L,静脉滴注4 h;后静脉滴注亚叶酸钙(CF)200 mg+0.9%氯化钠注射液250 m L,2 h内滴完;再持续静脉滴注2 600 mg/m2氟尿嘧啶(5-FU)46 h;重复给药不超过12次。B组第1天予L-OHP 200 mg+5%葡萄糖注射液2 500 m L,静脉滴注2 h;同时静脉滴注2 h CF 200 mg/m2+0.9%氯化钠注射液250 m L;待上述2种药物同时结束后,再连续静脉滴注6 h 5-FU 300 mg/m2+0.9%氯化钠注射液500 m L。结果 A组患者完全缓解8例,部分缓解20例,总有效率为46.67%(28/60),高于B组的26.67%(χ2=5.17,P〈0.05)。2组均未发现Ⅳ级严重毒性反应,B组严重毒性反应发生率高于A组,但无统计学差异(P〉0.05)。化学治疗药物毒性最主要表现为脱发,2组均为95.00%;其次是神经毒性和恶心/呕吐,A、B两组的发生率分别为60.00%比65.00%和58.33%比65.00%,但差异无统计学意义(P〉0.05)。A组完全依从,没有脱落病例,B组有3例患者中途退出研究,脱落率为5.00%,高于A组,但无显著性差异(P〉0.05)。结论奥沙利铂联合氟尿嘧啶、亚叶酸钙治疗转移性大肠癌的疗效确切,特别是经改良后的FOLFOX7方案更提高了临床疗效,提高了患者治疗依从性,药物毒性反应常见且轻微,值得临床推广。 相似文献
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Yoshio Katamura Hiroshi Aikata Yuki Kimura Tomokazu Kawaoka Shintaro Takaki Koji Waki Akira Hiramatsu Yoshiiku Kawakami Shoichi Takahashi Masaki Ishikawa Masashi Hieda Hideaki Kakizawa Kazuaki Chayama 《Journal of gastroenterology and hepatology》2010,25(6):1117-1122
Background and Aims: We investigated the efficacy of intra‐arterial 5‐fluorouracil (5‐FU) and systemic interferon (IFN)‐α (5‐FU‐IFN) in the treatment of hepatocellular carcinoma (HCC) with portal vein tumor thrombosis in the first branch or trunk (Vp3/4) and extrahepatic metastases. Methods: We examined 17 HCC patients with Vp3/4 and extrahepatic metastases (meta group) and 31 HCC patients with Vp3/4 (non‐meta group). Baseline intrahepatic tumor factors and the hepatic reserve were similar between groups. The extrahepatic metastases of the meta group were not considered prognostic factors. Following the administration of 5‐FU/IFN to all patients, we compared the survival rates, response, time to progression (TTP), and safety between groups. Results: For intrahepatic HCC, complete response, partial response, stable disease, progressive disease, and drop out were observed in no (0%), one (6%), seven (41%), nine (53%), and no (0%) patients of the meta group, and in five (16%), seven (23%), 13 (42%), five (16%) and one (3%) patient of the non‐meta group, respectively. The response rate was significantly lower in the meta group (6% vs 39%, P = 0.018). The median TTP of intrahepatic HCC and the median survival time were significantly shorter in the meta group than in the non‐meta group (1.6 vs 6.3 months, P = 0.0001, and 3.9 months vs 10.5 months, P < 0.0001, respectively). The multivariate analysis showed that the absence of extrahepatic metastases was a significant and independent determinant of both TTP of intrahepatic HCC (P < 0.001) and overall survival (P < 0.001). No patient died of extrahepatic HCC‐related disease. Conclusions: The efficacy of 5‐FU/IFN for advanced HCC with Vp3/4 and extrahepatic metastases was markedly limited. 相似文献
40.