甲硝唑/蒙脱土抗菌复合物的制备及体外缓释特征

目的:研究甲硝唑/蒙脱土抗菌复合物的制备及其体外释放特性.方法:以离子交换方式将甲硝唑插层到钠基蒙脱土的层间,通过XRD、FTIR及TG对抗茵复合物的性能进行表征,并通过体外释放试验检测缓释效果.结果:插层后,钠基蒙脱土层间距由1.2345 nm增大到1.3026 nm,说明甲硝唑已经插入钠基蒙脱土层间:通过体外释放试验检测证实抗茵复合物具有良好的缓释效果.结论:甲硝唑/蒙脱土抗茵复合物具有缓释作用,可进一步开发成抗感染缓释药物.     

壳聚糖-聚天冬氨酸-5氟尿嘧啶纳米粒子对小鼠的抑瘤作用

目的 制备包被壳聚糖-聚天冬氨酸-5氟尿嘧啶(CTS-Pasp-5FU)纳米粒子,观察其对裸鼠人胃癌SGC-7901移植瘤模型的治疗效应和不良反应.方法 通过离子凝胶化反应制备CTS-Pasp-5FU纳米粒子.选择24只裸鼠制备人胃癌SGC-7901移植肿瘤模型,根据注入药物不同均分为CTS-Pasp5FU组、5-FU组和0.9%氯化钠溶液组,观察治疗前和治疗后7、14、21 d药物对肿瘤的治疗效应及骨髓抑制等不良反应.结果 CTS-Pasp-5FU纳米粒子载药率和包封率分别为40.2%和34.9%.治疗后21 d,5-FU组、CTS-Pasp-5FU组肿瘤体积比0.9%氯化钠溶液组明显缩小(P＜0.01);5-FU组、CTS-Pasp-5FU组肿瘤生长抑制率为79.49%、81.10%,瘤重抑制率为65.30%、72.79%,组间比较差异均有统计学意义(P值均＜0.05).与0.9%氯化钠溶液组、CTS-Pasp-5FU组相比,5-FU组骨髓粒细胞-巨噬细胞集落形成单位形成数量明显降低(P＜0.01),总胆红素和ALT明显增高(P＜0.05);白细胞及肌酐水平各组相似(P＞0.05).结论 CTS-Pasp-5FU纳米粒子可显著提高5-FU对肿瘤的抑制作用,并有效降低骨髓抑制等不良反应.     

5-氟尿嘧啶及其药物前体在胃肠道肿瘤化疗中的应用

5、氟尿嘧啶(5-fluorouracil,5-FU)最早于1957年由Heidelberger等合成并投入临床使用[1],至今已经有近50年的历史,但目前它仍然是胃肠道肿瘤化学治疗中的最主要药物之一.5-FU具有针对上皮源性肿瘤的活性,在胃肠道肿瘤的应用中,与单药反应率在10～30%之间;在以5-FU为主的转移性结直肠癌的治疗中,可使平均中位生存期达到1年.     

曲安奈德联合5-氟尿嘧啶治疗瘢痕疙瘩疗效观察

目的观察曲安奈德联合5-氟尿嘧啶局部注射治疗瘢痕疙瘩的疗效及安全性。方法选取瘢痕疙瘩患者120例,随机分为观察组和对照组,每组60例。观察组给予曲安奈德联合5-氟尿嘧啶以及利多卡因治疗,对照组给予曲安奈德和利多卡因治疗,比较两组临床疗效。结果治疗后观察组疗效优于对照组,差异有统计学意义(P0.05)。两组不良反应发生率比较差异无统计学意义(P0.05)。治疗组复发率低于对照组(P0.05)。结论曲安奈德联合5-氟尿嘧啶治疗瘢痕疙瘩,疗效显著,复发少,值得临床推广应用。     

氯喹增强LOVO细胞对5-氟尿嘧啶化疗敏感性的作用

目的研究结肠癌细胞LOVO在氯喹(CQ)作用下对化疗药物5-氟尿嘧啶(5-FU)的敏感性变化及机制。方法用MTT法分别检测CQ和5-FU作用24 h和48 h对LOVO细胞的增殖抑制作用。实验分为4组:空白对照组、CQ组、5-FU组和联合作用组。CQ、5-FU及两者联合作用于LOVO细胞后,通过细胞划痕实验和Transwell分别检测细胞迁移和侵袭的变化,采用流式细胞术和TUNEL方法检测细胞凋亡,采用Western blot检测细胞自噬及凋亡相关蛋白的表达情况。结果在不同浓度CQ、5-FU作用下LOVO细胞增殖受到抑制,且呈现剂量依赖性,48 h时CQ和5-FU的IC50分别为11.8μg/ml和2.5μmol/L。与空白对照组相比,CQ、5-FU作用后细胞迁移率和细胞侵袭能力显著降低,且两药联用组的抑制效应更显著。流式细胞术检测显示,CQ组、5-FU组细胞凋亡率分别为(17.85±1.04)%、(17.36±0.96)%,显著高于空白对照组(4.11±0.23)%,两药联用组凋亡率为(25.03±2.27)%,两药联用组与CQ、5-FU单用组相比,细胞凋亡率更高,差异均有统计学意义(P<0.01)。TUNEL检测显示,CQ组、5-FU组细胞凋亡指数显著高于空白对照组,两药联用组与CQ、5-FU单用组相比细胞核凋亡指数更高。Western blot检测显示CQ和5-FU处理后导致P53、Bax、caspase3、caspase9和P62蛋白表达水平显著升高,而Bcl-2、LC3和Beclin-1蛋白表达水平则显著降低,差异均有统计学意义(P<0.01)。结论 CQ能抑制结直肠癌细胞LOVO的增殖、迁移、侵袭和自噬,促进其凋亡,并能增强细胞对化疗药物5-FU的敏感性。     

大肠癌根治术中5-氟尿嘧啶缓释剂间质化疗的安全性观察

目的探讨大肠癌术中5-氟尿嘧啶(5-Fu)缓释剂间质化疗的安全性。方法将190例大肠癌根治术患者分为治疗组94例和对照组96例。治疗组手术结束关腹前将5-Fu缓释剂600 mg均匀置于肿瘤病灶区域和淋巴血管回流区域;对照组术中不用化疗药。两组术后处理相同。术前及术后第2、12天检测两组白细胞和红细胞计数、血清ALT、Cr及CD4+/CD8+值,观察不良反应(恶心呕吐及腹痛、腹泻)及并发症(化学性腹膜炎、伤口感染、吻合口漏、出血、肠梗阻、盆腔积液等)发生情况,比较住院天数。结果两组手术前后各相关指标、不良反应及并发症发生率、住院天数比较均无显著差异。结论大肠癌根治术中采用5-Fu缓释剂行间质化疗较为安全。     

5-氟尿嘧啶对结肠癌干细胞干性和增殖的影响及相关机制

目的探讨5-氟尿嘧啶(5-FU)抑制结肠癌干细胞(CCSCs)干性对结肠癌细胞生长的影响及相关分子机制。方法将慢病毒介导的p53特异性短发来RNA(shRNA)转导入CCSCs,构建敲低p53表达的shRNA-p53-CCSCs细胞系。然后将正常CCSCs和shRNA-p53-CCSCs分别分成以下处理组:阴性对照组、DMSO组、舒林酸组和5-FU组,舒林酸组细胞经10μg/ml舒林酸处理,5-FU组细胞经2.5μg/ml 5-FU处理,然后通过BrdU检测试剂盒检测正常CCSCs和shRNA-p53-CCSCs活性,末端转移酶dUTP切口末端标记检测细胞凋亡情况,球体形成实验检测细胞干性变化,Western印迹检测处理后细胞中线粒体凋亡途径相关蛋白Bax/Bcl-2和细胞色素c,β-连环蛋白及其下游靶蛋白c-Myc和cyclinD1表达情况。结果与阴性对照组相比,5-FU组正常CCSCs增殖速率下降了52%,凋亡率为31%(P<0.05),而shRNA-p53-CCSCs增殖速率下降了73%,凋亡率为42%(P<0.05),舒林酸组正常CCSCs增殖速率下降了47%(P<0.05)。球体形成实验检测结果表明,5-FU和舒林酸均显著抑制CCSCs球体形成,且与阴性对照组相比,5-FU和舒林酸组球体体积显著下降(P<0.05),5-FU处理后正常CCSCs中Bax/Bcl-2比例升高约4倍,正常CCSCs与shRNA-p53-CCSCs中细胞色素c表达分别升高约2.8倍,2.5倍,β-连环蛋白在正常CCSCs的胞质和胞核中分别下降75%,73%,在shRNA-p53-CCSCs中分别下降81%,80%,而c-Myc和cyclinD1在上述两种细胞中的表达分别下降83%,52%和47%,53%。结论 5-FU能通过抑制Wnt/β-连环蛋白信号通路并上调线粒体介导的细胞凋亡抑制CCSCs增殖并促进细胞凋亡,具有潜在的抗肿瘤性。     

眼科用汉防已甲素联合5-氟尿嘧啶壳聚糖微球的制备及其质量评估

目的制备汉防已甲素（Tet）联合5-氟尿嘧啶（5-FU）壳聚糖缓释微球并观察微球质量。方法以壳聚糖为载体,采用乳化交联法制备Tet联合5-FU壳聚糖微球。在单因素考察的基础上,利用正交试验设计,优化微球制备工艺,并对制得微球的粒径、形态、工艺重复性及稳定性、体外突释情况等进行观察。结果制得的微球形态圆整,粒径为（80.4±1.34）μm,其中粒径60～100μm的微球占总数的89.5%;载药量：5-FU为10.42%,Tet为16.83%;微球包封率：5-FU为58.23%,Tet为47.02%;最佳工艺条件重复性良好。结论成功制备了Tet联合5-FU壳聚糖微球,其质量优良。     

中低位直肠癌术中应用5-氟尿嘧啶缓释剂的安全性

5-氟尿嘧啶(5-FU)缓释剂由于局部药物浓度高,持续时间长,在实体肿瘤的区域化疗中受到关注.本文采用术中局部应用5-FU缓释剂的方法,观察其在中低位直肠癌区域化疗中的安全性.     

5-氟尿嘧啶对老年鼻咽癌患者血浆EB病毒DNA水平的影响及临床疗效

目的探讨5-氟尿嘧啶(5-FU)对老年鼻咽癌患者血浆EB病毒DNA水平影响及对老年鼻咽癌患者的临床疗效。方法收集90例Ⅲ期和Ⅳ期鼻咽癌患者,随机分为实验组和对照组各45例。两组均给予放射治疗,实验组辅助给予5-FU治疗,荧光定量PCR反应监测患者治疗前后EB病毒DNA的变化,临床检查和MRI判断患者治疗后的临床疗效,进行对比分析。结果实验组较对照组临床有效率高(P=0.011)。对颈淋巴结转移患者,实验组较对照组有效率高(P=0.000)。实验组和对照组治疗后EBV DNA均较治疗前显著降低,实验组较对照组降低更明显(P0.05)。结论 5-FU能明显降低老年鼻咽癌患者血浆EBV DNA水平,提高患者的临床疗效。     

Coronary artery spasm induced by 5-fluorouracil

We report a case of coronary artery spasm induced by 5-fluorouracil. The symptoms occurred during continuous intravenous infusion of the drug, and a coronary spasm was visualized at angiography.     

Histological evaluation of colonic anastomotic healing in the rat following preoperative 5-fluorouracil, fractionated irradiation, and combined treatment

There is a growing interest in neoadjuvant chemo- and radiotherapy as a treatment modality for colorectal cancer which could affect mechanical and biochemical parameters of anastomotic healing. This study investigated the effect of such protocols on colonic anastomotic healing by evaluating the histopathological parameters. One hundred and sixty male Wistar rats were divided into six groups: a control group (I, n=20), a saline group (II, n=30) which received 1 ml NaC1 intraperitoneally, a sham-irradiated group (III, n=20), a 5-fluorouracil (5-FU) group (IV, n=30), which received 5-FU (20 mg/kg) intraperitoneally for 5 consecutive days, an irradiated group (V, n=40) which received fractionated irradiation to the whole pelvis to a totaldose of 22 Gy, 5.5 Gy per fraction on 4 consecutive days, and a concomitant 5-FU + irradiation group (VI, n=20) which received 5-FU as in group IV and irradiated as in group V. All groups underwent left colonic resection with primary anastomosis, and the last fraction of irradiation and the last injection were given 4 and 3 days before the operation, respectively. Within each group one half of the animals were killed on the third postoperative day and the other half on the seventh postoperative. day. After the resection of the anastomotic segments, histopathological examination was evaluated. Apposition of the wound edges of the mucosa and the muscularis were not affected by the therapy. The level of granulocytes was high, inflammatory exudate and necrosis persisted, granulation tissue formation was delayed, and the levels of macrophages and fibroblasts were low. We conclude that colonic anastomotic healing can be affected by the administration of preoperative chemotherapy, irradiation, and chemoirradiation. Accepted: 17 July 1998     

Reversible cardiogenic shock under 5-fluorouracil treatment

5-fluorouracil, an antimetabolite agent, has been widely used since 1957 for treatment of varied types of cancer such as gastro-intestinal, pancreas, breast, lung, head and neck malignancies. Cardiotoxicity of 5-fluorouracil is rare and was first described in 1975. It can induce severe complications and involve vital prognosis in the short-term. These complications are less known by cardiologists than medical oncologists. The following clinical case represents a potentially serious and rare case of completely reversible cardiogenic shock in a patient with a colo-rectal cancer. A better knowledge of these complications could reduce cases of death by an earlier diagnosis, and a better evaluation of patients with high cardiotoxicity risk.     

“Organic brain syndrome” secondary to 5-fluorouracil toxicity

A 68-year-old woman, who was treated with 5-fluorouracil (5-FU) intravenous therapy weekly for variable periods following hemicolectomy for adenocarcinoma of the cecum, had at least two well-described episodes of mental confusion, disorientation, and deterioration, in the absence of cerebellar tract signs. The sensorium cleared after cessation of 5-FU, only to deteriorate following readministration of the drug. She was thought to have organic brain syndrome during her most recent mental relapse. Her mental status has now been intact for more than one year since her last exposure to 5-FU. This is believed to be the third patient who has shown mental changes which could be attributable to 5-FU toxicity. Since 5-FU is the most frequently used chemotherapy for the treatment of colonic cancer, it is important that this form of toxicity be recognized lest subject patients be judged to have irreversible organic brain syndrome or metastatic carcinoma.     

Systemic gemcitabine combined with intra-arterial low-dose cisplatin and 5-fluorouracil for advanced hepatocellular carcinoma： Seven cases

The combination of intra-arterial low-dose cisplatin and 5-fluorouracil （5-FU） is effective against advanced hepatocellular carcinoma （HCC）. Systemic gemcitabine chemotherapy seems effective in many cancers. We report the results of combination therapy with systemic gemcitabine, intra-arterial low-dose cisplatin and 5-FU （GEMFP）. Seven patients with non-resectable advanced HCC were treated with GEMFP. One course of chemotherapy consisted of daily intra-arterial cisplatin （20 mg/body weight/hour on d 1, 10 mg/body weight per 0.5 h on d 2-5 and 8-12）, followed by 5-FU （250 mg/body weight per 5 h on d 1-5 and 8-12） via an injection port. Gemcitabine at 1000 mg/m2 was administered intravenously at 0.5 h on d 1 and 8. The objective response was 57%. The response to GEMFP was as follows： complete response （no patients）, partial response （four patients）, stable disease （three patients）, and progressive disease （no patients）. The median survival period was 8 mo （range, 5-55）. With regard to the National Cancer Institute Common Toxicity Criteria （NCI-CTC） grade 3 or 4 adverse reactions, seven （100%）, seven, six （86%） and one （14%） patients developed leukopenia, neutropenia, thrombocytopenia and anemia, respectively. GEMFP may potentially be effective for non- resectable advanced HCC, but it has severe hematologic toxicity.     

Modified irinotecan plus bolus 5-fluorouracil/L-leucovorin for metastatic colorectal cancer at a single institution in Japan

Background  The modified irinotecan plus bolus 5-fluorouracil/L-leucovorin (IFL) regimen (irinotecan plus bolus 5-fluorouracil/L-leucovorin) used to be one of the standard treatments for metastatic colorectal cancer until approval of oxaliplatin in Japan. We evaluated the efficacy of modified IFL therapy for Japanese patients. Methods  Forty-seven patients with metastatic colorectal cancer received irinotecan (100 mg/m²) and bolus 5-fluorouracil (500 mg/m²) plus L-leucovorin (10 mg/m²) on days 1 and 8 every 3 weeks until progression or unmanageable toxicity occurred. The data on toxicity and tumor response were analyzed retrospectively. Results  All patients discontinued modified IFL therapy due to cancer progression, except for one patient who developed severe liver dysfunction. The overall response rate was 25%. The median progression-free survival time (PFS) was 6.1 months. The median overall survival time (OS) was 17.4 months for all patients, 28.8 months for patients receiving subsequent oxaliplatin therapy, and 8.9 months for patients without oxaliplatin (P = 0.0031). According to multivariate analysis results, good performance status, a normal white cell count, and absence of local recurrence were associated with a better PFS. Tumor response was a good prognostic factor for both PFS and OS. Gastrointestinal symptoms were the most common toxicities, including grade 3 diarrhea (8%) and grade 3 anorexia (10%). Grade 4 neutropenia occurred in 6% of patients. No other drug-related severe adverse events or deaths were observed. Conclusions  Modified IFL therapy is an effective and well-tolerated regimen for Japanese patients with metastatic colorectal cancer. Modified IFL therapy combined with biological agents might remain an option for some patients who refuse a central venous catheter. An erratum to this article can be found at     

含CpG的寡脱氧核苷酸与5-氟尿嘧啶联用治疗小鼠肝癌

目的　探讨含CpG的寡脱氧核苷酸(ODN)单独及与5- 氟尿嘧啶(5 -FU)联用对小鼠移植性肝癌的治疗作用。方法　Balb/c小鼠皮下接种肝癌H22 细胞建立荷瘤鼠模型,肿瘤周围皮下分别注射生理盐水(对照组)、无CpG ODN、5 -FU、CpG ODN和CpG ODN+5 FU后,定期测量肿瘤大小。用酶联免疫吸附实验检测鼠血清白细胞介素(IL)- 12和干扰素(IFN) -γ含量;用乳酸脱氢酶释放法检测鼠脾脏自然杀伤(NK)细胞活性。结果　与对照组肿瘤体积[(6710±910) mm3 ]比较, CpG ODN、CpGODN+5- FU及单用5 -FU治疗后,肿瘤体积分别为(3579±481) mm3、(1998±474) mm3 及(2124±434) mm3(P值均<0.01)。对照组鼠血清IL -12 和IFN -γ的含量分别为(238±45) pg/ml和(57±8)pg/ml,与CpG ODN组[IL 12:(464±24) pg/ml;IFN -γ:(134±26) pg/ml]及CpG ODN+5 -FU组[IL -12:(336±29) pg/ml;IFN -γ:(111±5) pg/ml]比较,差异有统计学意义(P值均<0.05)。CpG ODN+5- FU组小鼠血清IL- 12及IFN -γ水平显著高于5- FU组[IL 12:(167±53) pg/ml;IFN -γ:(53±17) pg/ml;P<0.05]。与对照组NK细胞的杀伤活性[(19.2±1.0)%]相比,CpG ODN组[(44.0±1.4)%]及CpG ODN+5 FU组[(30.7±1.3)%]显著增强(P值均<0.05),且CpG ODN+5 FU组显著高于5- FU治疗组[(12.0     

内镜化疗粒子植入缓解晚期食管癌梗阻症状的临床研究

目的对16例晚期食管癌导致的食管管腔梗阻患者行内镜下缓释5-氟尿嘧啶（5-Fu）粒子植入治疗,观察其缓解梗阻的疗效。方法胃镜下对食管癌梗阻部结节及浸润处多点或密集型植入5-Fu缓释粒子。结果16例患者施行粒子植入治疗后,缓解梗阻有效14例,无效2例,总有效率87．5％。内镜下缓释5-FU粒子植入治疗未发生出血、穿孔等并发症及恶心、呕吐、腹痛、发热等不良反应,肝、肾功能及血常规检查未见异常。结论内镜下缓释5-FU粒子植入治疗是缓解晚期食管癌患者梗阻症状安全、有效的方法。