The antitumor activity of 5 fluorouracil 1 acetic acid(HFAA) and its lanthanide complexes(La(FAA) 3, Eu(FAA) 3) were studied. The results show that HFAA, La(FAA) 3 and Eu(FAA) 3 with the concentrations of 1 0&...The antitumor activity of 5 fluorouracil 1 acetic acid(HFAA) and its lanthanide complexes(La(FAA) 3, Eu(FAA) 3) were studied. The results show that HFAA, La(FAA) 3 and Eu(FAA) 3 with the concentrations of 1 0×10 -5 ～1 0×10 -2 μg·ml -1 inhibit the colony formation of leukemia cells(L 1210 ) and the growth of transplanted tumor sarcoma 180(S 180 ), hepatic carcinoma(HEPA) and ehrlich ascites tumor(EC) as well. The maximum inhibitory rate of Eu(FAA) 3 for S 180 is 38 4%, that HFAA and La(FAA) 3 for EC are 22 4% and 43 4%, respectively. The life prolongation rate of Eu(FAA) 3 for HEPA bearing mice is as long as 284%.展开更多
Neoadjuvant chemotherapy plus radiotherapy is the most common treatment regimen for advanced nasopharyngeal carcinoma(NPC).Whether chronomodulated infusion of chemotherapy can reduce its toxicity is unclear.This study...Neoadjuvant chemotherapy plus radiotherapy is the most common treatment regimen for advanced nasopharyngeal carcinoma(NPC).Whether chronomodulated infusion of chemotherapy can reduce its toxicity is unclear.This study aimed to evaluate the toxic and therapeutic effects of sinusoidal chronomodulated infusion versus flat intermittent infusion of cisplatin(DDP)and 5-fluorouracil(5-FU)followed by radiotherapy in patients with locoregionally advanced NPC.Patients with biopsy-diagnosed untreated stages III and IV NPC(according to the 2002 UICC staging system)were randomized to undergo2 cycles of sinusoidal chronomodulated infusion(Arm A)or flat intermittent constant rate infusion(Arm B)of DDP and 5-FU followed by radical radiotherapy.Using a"MELODIE"multi-channel programmed pump,the patients were given 12-hour continuous infusions of DDP(20 mg/m2)and 5-FU(750 mg/m2)for 5days,repeated every 3 weeks for 2 cycles.DDP was administered from 10:00 am to 10:00 pm,and 5-FU was administered from 10:00 pm to 10:00 am each day.Chronomodulated infusion was performed in Arm A,with the peak deliveries of 5-FU at 4:00 am and DDP at 4:00 pm.The patients in Arm B underwent a constant rate of infusion.Radiotherapy was initiated in the fifth week,and both arms were treated with the same radiotherapy techniques and dose fractions.Between June 2004 and June 2006,125 patients were registered,and 124 were eligible for analysis of response and toxicity.The major toxicity observed during neoadjuvant chemotherapy was neutropenia.The incidence of acute toxicity was similar in both arms.During radiotherapy,the incidence of stomatitis was significantly lower in Arm A than in Arm B(38.1%vs.59.0%,P=0.020).No significant differences were observed for other toxicities.The 1-,3-,and 5-year overall survival rates were 88.9%,82.4%,and 74.8%for Arm A and 91.8%,90.2%,and 82.1%for Arm B.The 1-,3-,and 5-year progression-free survival rates were 91.7%,88.1%,and 85.2%for Arm A and 100%,94.5%,and 86.9%for Arm B.The 1-,3-,and 5-year distant metastasis-free survival rates were 82.5%,79.1%,and 79.1%for Arm A and 90.2%,85.2%,and 81.7%for Arm B.Chronochemotherapy significantly reduced stomatitis but was not superior to standard chemotherapy in terms of hematologic toxicities and therapeutic response.展开更多
The sustained-release properties of the biodegradable nano-drug delivery systems were used to improve the residence time of the chemotherapeutic agent in the body. These drug delivery systems were widely used to deliv...The sustained-release properties of the biodegradable nano-drug delivery systems were used to improve the residence time of the chemotherapeutic agent in the body. These drug delivery systems were widely used to deliver chemotherapeutic drugs. The 5-fluorouracil loaded chitosan nanoparticles prepared in this paper have the above advantage. Here, we found that when the mass ratio of 5-fluorouracil and chitosan was 1:1, the maximum drug loading of nanoparticles was 20.13 ± 0.007%, the encapsulation efficiency was 44.28 ± 1.69%, the particle size was 283.9 ± 5.25 nm and the zeta potential was 45.3 ± 3.23 mV. The prepared nanoparticles had both burst-release and sustained-release phases in vitro release studies.In addition, the inhibitory effect of the prepared nanoparticles on gastric cancer SGC-7901 cells was similar to that of 5-fluorouracil injection, and the blank vector had no obvious inhibitory effect on SGC-7901 cells. In the pharmacokinetic study of rats in vivo, we found that AUC(0-t), MRT(0-t) and t1/2 z of nanoparticles were significantly increased in vivo compared with 5-fluorouracil solution, indicating that the prepared nanoparticles can play a role in sustained-release.展开更多
探究秦川牛宰后成熟过程中线粒体Tu翻译延长因子(mitochondrial Tu translation elongation factor,TUFM)表达对肉的持水性影响。以秦川牛背最长肌为研究对象,测定4℃不同成熟时间下的pH值、贮藏损失、离心损失、蒸煮损失、水分分布、...探究秦川牛宰后成熟过程中线粒体Tu翻译延长因子(mitochondrial Tu translation elongation factor,TUFM)表达对肉的持水性影响。以秦川牛背最长肌为研究对象,测定4℃不同成熟时间下的pH值、贮藏损失、离心损失、蒸煮损失、水分分布、肌原纤维蛋白等指标变化情况,测定不同成熟时间(0、96、192 h)下TUFM表达量及其含量、Beclin1蛋白表达量。结果显示:在秦川牛宰后成熟期间,肌原纤维蛋白发生降解,TUFM的表达量与Beclin1蛋白表达量和牛肉的持水性存在密切关系,其中蛋白质组学测定的TUFM表达量变化与TUFM含量变化趋势一致,Beclin1蛋白表达量、贮藏损失、离心损失、蒸煮损失整体均呈先上升后下降趋势,pH值呈先下降后上升趋势;Pearson相关性分析表明,牛背最长肌中TUFM表达量与低场核磁共振峰面积比P_(2b)、Beclin1蛋白表达量呈极显著正相关(P<0.01),与贮藏损失、离心损失、蒸煮损失呈显著正相关(P<0.05),与P_(21)呈极显著负相关(P<0.01),与P_(22)呈显著负相关(P<0.05),与pH值无显著相关性(P>0.05)。通过蛋白质组学鉴定出23种与TUFM相关的差异蛋白,通过基因本体论、京都基因与基因组百科全书通路分析发现,差异蛋白可通过多种途径参与能量代谢,进而介导细胞自噬;对差异蛋白和持水性指标进行Pearson相关性分析发现,有5种差异蛋白(ATP5F1D、EEF1A2、GSPT1、NDUFB5、SUCLG1)与持水性指标具有显著相关性(P<0.05、P<0.01)。分析可知,包括TUFM在内,共6种蛋白主要通过能量代谢和氧转运等途径正向或负向影响细胞自噬,从而影响肉的持水性。展开更多
Resistance to 5-fluorouracil(5-FU), an important anticancer drug, is a serious challenge in the treatment of pancreatic cancer. Equilibrative nucleoside transporter 1 and multidrug-resistance protein(MRP) 5 and MRP8, ...Resistance to 5-fluorouracil(5-FU), an important anticancer drug, is a serious challenge in the treatment of pancreatic cancer. Equilibrative nucleoside transporter 1 and multidrug-resistance protein(MRP) 5 and MRP8, rather than P-glycoprotein, play important roles in 5-FU transport. Thymidylate synthase, dihydropyrimidine dehydrogenase, methylenetetrahydrofolate reductase and thymidine phosphorylase are four key enzymes involved in 5-FU metabolism. Other metabolic enzymes, including uridine monophosphate synthetase, also contribute to chemoresistance. Intracellular signaling pathways are an integrated network, and nuclear factor kappa-light-chain-enhancer of activated B cells, AKT and extracellular signal-regulated kinases are signaling pathways that are particularly relevant to 5-FU resistance. In addition, recent reports indicate that STAT-3 is a crucial survival protein. Proteomic assays provide a powerful tool for identifying target proteins and understanding the role of micro RNAs and stromal factors to facilitate the development of strategies to combat 5-FU resistance.展开更多
A novel tungstosilicic polyoxometalate containing 5-fluorouracil and Nd, K26(C4H4FN2O2)8Nd(SiW11O39)4·5H2O (FNSW) was synthesized and its structure was characterized by using elemental analysis, FT-IR spectra, X-...A novel tungstosilicic polyoxometalate containing 5-fluorouracil and Nd, K26(C4H4FN2O2)8Nd(SiW11O39)4·5H2O (FNSW) was synthesized and its structure was characterized by using elemental analysis, FT-IR spectra, X-ray powder diffraction, UV-vis spectra and TG. The results indicated that the compound FNSW had Keggin structure of heteropolyanion and ring structure of 5-fluorouracil, and it had a good thermal stability. With 5-fluorouracil for the positive control group, the cytotoxicity tests in human renal embryonic cell HEK293 and the antitumor activity tests in hepatocellular carcinoma cell HepG-2 were carried out by the methyl thiazolyl tetrazolium method. The toxicity of the compound FNSW was lower than that of 5-fluorouracil, and compared with 5-fluorouracil the compound FNSW could inhibit HepG-2 cell in vitro with significant difference. The rare earth element Nd increased the biological activity of polyoxometalate significantly.展开更多
A new series of N^1-acetylamino-（5-alkyl/aryl- 1,3,4-thiadiazole-2-yl）-5-fluorouracil derivatives were designed and synthesized. These compounds have not been reported in literature, and their structure chemical wer...A new series of N^1-acetylamino-（5-alkyl/aryl- 1,3,4-thiadiazole-2-yl）-5-fluorouracil derivatives were designed and synthesized. These compounds have not been reported in literature, and their structure chemical were confirmed by IR, ^1H NMR and MS （HRMS）. The results of antitumor inhibitory activity test showed that some compounds possess more potent antitumor inhibitory activity than 5-fluorouracil.展开更多
The title compound, [Cu（C6H4N2O4F）2（H2O）4].4（H2O） I, has been hydrothermally synthesized and structurally determined by single-crystal X-ray diffraction method. It crystallizes in monoclinic, space group P21/c w...The title compound, [Cu（C6H4N2O4F）2（H2O）4].4（H2O） I, has been hydrothermally synthesized and structurally determined by single-crystal X-ray diffraction method. It crystallizes in monoclinic, space group P21/c with a = 8.3041（17）, b = 12.045（2）, c = 11.077（2） A, β = 92.567（3）°, V= 1106.8（4） A^3, Mr = 581.89, Z= 2, Dc = 1.746 g/cm^3, F（000） = 598,μ（MoKa） = 1.090 mm^-1, the final R = 0.0296 and wR = 0.0806 for 3195 observed reflections with Ⅰ 〉 2σ（Ⅰ）. In the centrosymmetric compound I, each Cu（Ⅱ） ion is coordinated by six O atoms from two 5-fluorouracil-1-acetate anions and four water molecules, forming a six-coordinated octahedral environment. N-H…O and O-H…O hydrogen-bonding interactions are observed in the structure, leading to the formation of a three-dimensional network.展开更多
Objective： To study the combined antitumor effect and possible mechanisms of ursolic acid with 5-fluorouracil （5-FU） on human esophageal carcinoma cell Eca-109 in vitro. Methods： Eca-109 cells were treated with ur...Objective： To study the combined antitumor effect and possible mechanisms of ursolic acid with 5-fluorouracil （5-FU） on human esophageal carcinoma cell Eca-109 in vitro. Methods： Eca-109 cells were treated with ursolic acid （10-50 μmol/L） and/or 5-fluorouracil （48.0-768.8 μmol/L） for 48 h in vitro. And then cell proliferation was determined by MTT assay. Cell cycle and apoptosis rate were analyzed by flow cytometry （FCM）. The morphological changes of apoptosis were observed by fluorescent microscopy. At last the expression of P27kipl, bcl-2 and bax were detected by western blot. Results： Results： In comparison with single agent treatment, the combination of ursolic acid and 5-fluorouracil produced greater efficacy in growth inhibition, cell cycle arrest at G0/G1 phase, and apoptosis induction （P〈0.05）. Western blot analysis showed that the combination use of ursolic acid and 5-fluorouracil suppressed the expression of bcl-2 and increased the expressions of bax and P27kip1. Conclusion： Ursolic acid combined with 5-fluorouracil showed adjuvant antiproliferative effects on human esophageal carcinoma cell Eca-109 in vitro, which mainly due to the induction of cell cycle arrest as well as apoptosis.展开更多
The geometries,electronic structure,IR spectrum and other properties of hydrogen interaction between 5-fluorouracil and glycine were studied at the B3LYP/6-31＋G＊ level.Single point energy calculations were executed ...The geometries,electronic structure,IR spectrum and other properties of hydrogen interaction between 5-fluorouracil and glycine were studied at the B3LYP/6-31＋G＊ level.Single point energy calculations were executed at the B3LYP/6-311＋＋G＊＊ and B3LYP/aug-cc-pvdz levels,and natural bond orbital （NBO） analysis was carried out at the B3LYP/6-31＋G＊ level.Finally,the hydrogen bonds were discussed via AIM electronic density topology analysis.展开更多
In order to explore whether the conventional use of 5 fluorouracil (5 Fu) had any toxic effects on trabecular meshwork cells, bovine trabecular meshwork cells were cultured in vitro and exposed to 5 Fu at different...In order to explore whether the conventional use of 5 fluorouracil (5 Fu) had any toxic effects on trabecular meshwork cells, bovine trabecular meshwork cells were cultured in vitro and exposed to 5 Fu at different concentrations. The cellular morphology, ultrastructure, mortality and phagocytosis were studied under light microscopy, transmission electron microscopy and methods of Wright's stain. It was found that the toxic effects of 5 Fu on the cells were in a dose dependent mode. 1×10 -1 mg/ml of 5 Fu caused a large part of cells rounded up, while 1×10 -3 mg/ml of the drug only a rough appearance of the cell surface. Exposure to 1×10 -2 mg/ml of 5 Fu made mitochrone swollen and rough endoplasmic reticulum enlarged, with the cell mortality being 50.5 %. The latex microspheres engulfed in cytoplasm in cells receiving 1×10 -1 and 1×10 -2 mg/ml of 5 Fu were significantly decreased as compared with those in the control group ( P <0.01). It was concluded that the safe concentration of 5 Fu on bovine trabecular meshwork cells was 1×10 -3 mg/ml and the conventional dosage of 5 Fu in clinical practice would not cause injury to trabecular meshwork cells.展开更多
AIM:There are conflicting data about p53 function on cellular sensitivity to the cytotoxic action of 5-fluorouracil (5-FU). Therefore the objective of this study was to determine the combined effects of adenovirus-med...AIM:There are conflicting data about p53 function on cellular sensitivity to the cytotoxic action of 5-fluorouracil (5-FU). Therefore the objective of this study was to determine the combined effects of adenovirus-mediated wild-type (wt) p53 gene transfer and 5-FU chemotherapy on pancreatic cancer cells with different p53 gene status. METHODS:Human pancreatic cancer cell lines Capan-1^(p53mut), Capan-2^(p53wt),FAMPAC^(p53mut),PANC1^(p53mut),and rat pancreatic cancer cell lines AS^(p53wt) and DSL6A^(p53null) were used for in vitro studies.Following infection with different ratios of Ad- p53-particles (MOI) in combination with 5-FU,proliferation of tumor cells and apoptosis were quantified by cell proliferation assay (WST-1) and FACS (PI-staining).In addition,DSL6A syngeneic pancreatic tumor cells were inoculated subcutaneously in to Lewis rats for in vivo studies. Tumor size,apoptosis (TUNEL) and survival were determined. RESULTS:Ad-p53 gene transfer combined with 5-FU significantly inhibited tumor cell proliferation and substantially enhanced apoptosis in all four cell lines with an alteration in the p53 gene compared to those two cell lines containing wt-p53.In vivo experiments showed the most effective tumor regression in animals treated with Ad-p53 plus 5-FU.Both in vitro and in vivo analyses revealed that a sublethal dose of Ad-p53 augmented the apoptotic response induced by 5-FU. CONCLUSION:Our results suggest that Ad-p53 may synergistically enhance 5-FU-chemosensitivity most strikingly in pancreatic cancer cells lacking p53 function.These findings illustrate that the anticancer efficacy of this combination treatment is dependent on the p53 gene status of the target tumor cells.展开更多
AIM: To evaluate the role of thymidine phosphorylase (TP) in cholangiocarcinoma using small interfering RNA (siRNA). METHODS: A human cholangiocarcinoma-derived cell line KKU-M139, which has a naturally high level of ...AIM: To evaluate the role of thymidine phosphorylase (TP) in cholangiocarcinoma using small interfering RNA (siRNA). METHODS: A human cholangiocarcinoma-derived cell line KKU-M139, which has a naturally high level of endogenous TP, had TP expression transiently knocked down using siRNA. Cell growth, migration, in vitro angiogenesis, apoptosis, and cytotoxicity were assayed in TP knockdown and wild-type cell lines. RESULTS: TP mRNA and protein expression were decreased by 87.1% ± 0.49% and 72.5% ± 3.2%, respectively, compared with control cells. Inhibition of TP significantly decreased migration of KKU-M139, and suppressed migration and tube formation of human umbilical vein endothelial cells. siRNA also reduced the ability of TP to resist hypoxia-induced apoptosis, while suppression of TP reduced the sensitivity of KKU-M139 to 5-fluorouracil. CONCLUSION: Inhibition of TP may be beneficial in decreasing angiogenesis-dependent growth and migration of cholangiocarcinoma but may diminish the response to 5-fluorouracil chemotherapy.展开更多
In order to improve the cancer-targeting and selective activity of antineoplastic agent [5-fluorouracil (5-FU)], a novel pH-responsive drug delivery system [pullulan acetate/sulfonamide (PA/SDM) conjugate] was syn- th...In order to improve the cancer-targeting and selective activity of antineoplastic agent [5-fluorouracil (5-FU)], a novel pH-responsive drug delivery system [pullulan acetate/sulfonamide (PA/SDM) conjugate] was syn- thesized by a diafiltration method. Sulfonamide was grafted to the hydrophobically modified pullulan acetate to enhance the pH sensitivity for better cancer-targeting delivery. 5-FU was loaded into the self-assembled nanoparti- cles by the same method. The drug-loaded self-assembled nanoparticles were successfully obtained and character- ized in terms of particle size, morphology and drug loading and release profile at various pHs. The results showed that the mean diameter of the self-assembled particles was approximately 100nm, with uniform size and good spherical morphology. The nanoparticles showed good stability at pH 7.4, which is equal to that of the normal body fluid, but shrank and aggregated below pH 6.8, which is close to the pH with tumors. The loading efficiency and concentration of released 5-FU was monitored at 269 nm on the UV/Vis spectrophotometer. The release profile was heavily pH-dependent around physiological pH, and the release rate was significantly enhanced under pH of 6.8.展开更多
Two novel rare earth substituted phosphotungstates containing 5-fluorouracil,K 9（C 4 H 4 FN 2 O 2） 2 Nd（PW 11 O 39） 2 ·25H 2 O（FNdPW） and K 9（C 4 H 4 FN 2 O 2） 2 Ce（PW 11 O 39） 2 ·23H 2 O（FCePW）,...Two novel rare earth substituted phosphotungstates containing 5-fluorouracil,K 9（C 4 H 4 FN 2 O 2） 2 Nd（PW 11 O 39） 2 ·25H 2 O（FNdPW） and K 9（C 4 H 4 FN 2 O 2） 2 Ce（PW 11 O 39） 2 ·23H 2 O（FCePW）,were synthesized and characterized by elementary analysis,FT-IR spectra,X-ray powder diffraction and 1 H NMR.The thermal analysis showed that FNdPW decomposed at 210 and 493 oC,and FCePW decomposed at 223 and 471 oC,both of which had good thermal stabilities.MTT tests were performed to study the antitumor activities against HeLa cells and HepG-2 cells of FNdPW,FCePW,5-fluorouracil,C 4 H 4 FN 2 O 2 H 2 PW 12 O 40 ·8H 2 O and K 11 Ln（PW 11 O 39） 2 ·xH 2 O（Ln=Nd,Ce）,and their cytotoxicities against HEK 293 cells.The results showed that FNdPW and FCePW possessed higher antitumor activities and lower cytotoxicities than those of 5-fluorouracil and C 4 H 4 FN 2 O 2 H 2 PW 12 O 40 ·8H 2 O,of which FNdPW exhibited the highest antitumor activates against HeLa cells（EC 50 =3.41×10-6 mol/L） and HepG-2 cells（EC 50 =6.24×10-6 mol/L）.Thus the introduction of rare earth elements and 5-fluorouracil could significantly enhance antitumor effect of polyoxometalates.展开更多
Chemotherapy with continuous infusion of 5-fluorouracil and cisplatin in a monthly schedule is one of the most common regimens in the treatment of advanced gastric cancer. In this study, we evaluated the efficacy and ...Chemotherapy with continuous infusion of 5-fluorouracil and cisplatin in a monthly schedule is one of the most common regimens in the treatment of advanced gastric cancer. In this study, we evaluated the efficacy and safety of a dosedense administration of this regimen in this patient population. Sixty-six consecutive patients with previously untreated histologically confirmed unresectable or metastatic gastric adenocarcinoma were treated with a 2-hour infusion of cisplatin 100 mg/m2 followed by continuous infusion of 5-fluorouracil 1000 mg/m2/day for 5 days, every 21 days. The most common grade ≥3 toxicities were fatigue (42%), nausea/vomiting (30%) and leucopenia (12%). Four patients (6%) died from treatment-related toxicity. The response rate was 35%, the median progression-free survival was 4.3 months and the median survival was 5.9 months. In light of these results, the dose-dense approach seems to offer little, if any, benefit compared with the standard regimens.展开更多
The objective of this study was to investigate the potential of methoxy polyethylene glycol（m PEG）grafted chitosan（m PEG-g-CS） to be used as a drug carrier. m PEG-g-CS was successfully synthesized by one-step meth...The objective of this study was to investigate the potential of methoxy polyethylene glycol（m PEG）grafted chitosan（m PEG-g-CS） to be used as a drug carrier. m PEG-g-CS was successfully synthesized by one-step method with formaldehyde. The substitution degree of m PEG on chitosan was calculated by elemental analysis and was found to be（3.23 0.25）%. m PEG-g-CS self-assembled micelles were prepared by ultrasonic method with the controlled size of 178.5–195.1 nm and spherical morphology. Stable dispersion of the micelles was formed with the zeta potential of 2.3–30.2 m V. 5-Fluorouracil（5-FU）, an anticancer chemotherapy drug, was used as a model drug to evaluate the efficiency of the new drug delivery carrier. The loading efficiency of 5-FU was（4.01 0.03）%, and the drug-loaded m PEG-g-CS self-assembled micelle showed a controlled-release effect. In summary, the m PEG-g-CS self-assembled micelle is proved to be a promising carrier with controlled particle size and controlled-release effect. Therefore, it has great potential for the application as 5-FU carriers for effective anti-tumor activity.展开更多
Objective： We aimed to investigate the safety and efficiency of vinorelbine/epirubidn/fluorouracil （NEF） regimen as adjuvant chemotherapy for breast cancer. Methods： From 2005 to 2008, 227 female breast cancer pat...Objective： We aimed to investigate the safety and efficiency of vinorelbine/epirubidn/fluorouracil （NEF） regimen as adjuvant chemotherapy for breast cancer. Methods： From 2005 to 2008, 227 female breast cancer patients were treated with the NEF regimen： vinorelbine 25 mg/m^2 iv on days 1 and 8; epirubicin 60 mg/m2 iv gtt on day 1; 5-Fu 500 mg/m2 iv gtt on day 1. Chemotherapy was repeated every 21-28 days for a total of 6 cycles. Results： The major side effects were neutrope- nia and gastrointestinal syndrome, with a 5-year survival rate of 85.4%, Conclusion： NEF regimen is safe and guarantees a high survival rate which could be recommended as a adjuvant chemotherapy regimen for breast cancer,展开更多
文摘The antitumor activity of 5 fluorouracil 1 acetic acid(HFAA) and its lanthanide complexes(La(FAA) 3, Eu(FAA) 3) were studied. The results show that HFAA, La(FAA) 3 and Eu(FAA) 3 with the concentrations of 1 0×10 -5 ～1 0×10 -2 μg·ml -1 inhibit the colony formation of leukemia cells(L 1210 ) and the growth of transplanted tumor sarcoma 180(S 180 ), hepatic carcinoma(HEPA) and ehrlich ascites tumor(EC) as well. The maximum inhibitory rate of Eu(FAA) 3 for S 180 is 38 4%, that HFAA and La(FAA) 3 for EC are 22 4% and 43 4%, respectively. The life prolongation rate of Eu(FAA) 3 for HEPA bearing mice is as long as 284%.
基金supported by a grant from the Principal Research Program of Clinical Disciplines of State Health Ministry(No.321)
文摘Neoadjuvant chemotherapy plus radiotherapy is the most common treatment regimen for advanced nasopharyngeal carcinoma(NPC).Whether chronomodulated infusion of chemotherapy can reduce its toxicity is unclear.This study aimed to evaluate the toxic and therapeutic effects of sinusoidal chronomodulated infusion versus flat intermittent infusion of cisplatin(DDP)and 5-fluorouracil(5-FU)followed by radiotherapy in patients with locoregionally advanced NPC.Patients with biopsy-diagnosed untreated stages III and IV NPC(according to the 2002 UICC staging system)were randomized to undergo2 cycles of sinusoidal chronomodulated infusion(Arm A)or flat intermittent constant rate infusion(Arm B)of DDP and 5-FU followed by radical radiotherapy.Using a"MELODIE"multi-channel programmed pump,the patients were given 12-hour continuous infusions of DDP(20 mg/m2)and 5-FU(750 mg/m2)for 5days,repeated every 3 weeks for 2 cycles.DDP was administered from 10:00 am to 10:00 pm,and 5-FU was administered from 10:00 pm to 10:00 am each day.Chronomodulated infusion was performed in Arm A,with the peak deliveries of 5-FU at 4:00 am and DDP at 4:00 pm.The patients in Arm B underwent a constant rate of infusion.Radiotherapy was initiated in the fifth week,and both arms were treated with the same radiotherapy techniques and dose fractions.Between June 2004 and June 2006,125 patients were registered,and 124 were eligible for analysis of response and toxicity.The major toxicity observed during neoadjuvant chemotherapy was neutropenia.The incidence of acute toxicity was similar in both arms.During radiotherapy,the incidence of stomatitis was significantly lower in Arm A than in Arm B(38.1%vs.59.0%,P=0.020).No significant differences were observed for other toxicities.The 1-,3-,and 5-year overall survival rates were 88.9%,82.4%,and 74.8%for Arm A and 91.8%,90.2%,and 82.1%for Arm B.The 1-,3-,and 5-year progression-free survival rates were 91.7%,88.1%,and 85.2%for Arm A and 100%,94.5%,and 86.9%for Arm B.The 1-,3-,and 5-year distant metastasis-free survival rates were 82.5%,79.1%,and 79.1%for Arm A and 90.2%,85.2%,and 81.7%for Arm B.Chronochemotherapy significantly reduced stomatitis but was not superior to standard chemotherapy in terms of hematologic toxicities and therapeutic response.
基金supported by the Anhui Provincial Natural Science Foundation (grant number 1508085QH194)
文摘The sustained-release properties of the biodegradable nano-drug delivery systems were used to improve the residence time of the chemotherapeutic agent in the body. These drug delivery systems were widely used to deliver chemotherapeutic drugs. The 5-fluorouracil loaded chitosan nanoparticles prepared in this paper have the above advantage. Here, we found that when the mass ratio of 5-fluorouracil and chitosan was 1:1, the maximum drug loading of nanoparticles was 20.13 ± 0.007%, the encapsulation efficiency was 44.28 ± 1.69%, the particle size was 283.9 ± 5.25 nm and the zeta potential was 45.3 ± 3.23 mV. The prepared nanoparticles had both burst-release and sustained-release phases in vitro release studies.In addition, the inhibitory effect of the prepared nanoparticles on gastric cancer SGC-7901 cells was similar to that of 5-fluorouracil injection, and the blank vector had no obvious inhibitory effect on SGC-7901 cells. In the pharmacokinetic study of rats in vivo, we found that AUC(0-t), MRT(0-t) and t1/2 z of nanoparticles were significantly increased in vivo compared with 5-fluorouracil solution, indicating that the prepared nanoparticles can play a role in sustained-release.
基金Supported by The Research Special Fund for the Public Welfare Industry of Health(The Translational Research of Early Diagnosis and Comprehensive Treatment in Pancreatic Cancer,201202007)
文摘Resistance to 5-fluorouracil(5-FU), an important anticancer drug, is a serious challenge in the treatment of pancreatic cancer. Equilibrative nucleoside transporter 1 and multidrug-resistance protein(MRP) 5 and MRP8, rather than P-glycoprotein, play important roles in 5-FU transport. Thymidylate synthase, dihydropyrimidine dehydrogenase, methylenetetrahydrofolate reductase and thymidine phosphorylase are four key enzymes involved in 5-FU metabolism. Other metabolic enzymes, including uridine monophosphate synthetase, also contribute to chemoresistance. Intracellular signaling pathways are an integrated network, and nuclear factor kappa-light-chain-enhancer of activated B cells, AKT and extracellular signal-regulated kinases are signaling pathways that are particularly relevant to 5-FU resistance. In addition, recent reports indicate that STAT-3 is a crucial survival protein. Proteomic assays provide a powerful tool for identifying target proteins and understanding the role of micro RNAs and stromal factors to facilitate the development of strategies to combat 5-FU resistance.
基金Project supported by the Chemical Materials Institute, China Academy of Engineering Physicsthe Doctoral Innovation Research Assistance Program of the Science and Technology Review
文摘A novel tungstosilicic polyoxometalate containing 5-fluorouracil and Nd, K26(C4H4FN2O2)8Nd(SiW11O39)4·5H2O (FNSW) was synthesized and its structure was characterized by using elemental analysis, FT-IR spectra, X-ray powder diffraction, UV-vis spectra and TG. The results indicated that the compound FNSW had Keggin structure of heteropolyanion and ring structure of 5-fluorouracil, and it had a good thermal stability. With 5-fluorouracil for the positive control group, the cytotoxicity tests in human renal embryonic cell HEK293 and the antitumor activity tests in hepatocellular carcinoma cell HepG-2 were carried out by the methyl thiazolyl tetrazolium method. The toxicity of the compound FNSW was lower than that of 5-fluorouracil, and compared with 5-fluorouracil the compound FNSW could inhibit HepG-2 cell in vitro with significant difference. The rare earth element Nd increased the biological activity of polyoxometalate significantly.
文摘A new series of N^1-acetylamino-（5-alkyl/aryl- 1,3,4-thiadiazole-2-yl）-5-fluorouracil derivatives were designed and synthesized. These compounds have not been reported in literature, and their structure chemical were confirmed by IR, ^1H NMR and MS （HRMS）. The results of antitumor inhibitory activity test showed that some compounds possess more potent antitumor inhibitory activity than 5-fluorouracil.
基金This work was supported by the National Natural Science Foundation of China (No. 20571057)
文摘The title compound, [Cu（C6H4N2O4F）2（H2O）4].4（H2O） I, has been hydrothermally synthesized and structurally determined by single-crystal X-ray diffraction method. It crystallizes in monoclinic, space group P21/c with a = 8.3041（17）, b = 12.045（2）, c = 11.077（2） A, β = 92.567（3）°, V= 1106.8（4） A^3, Mr = 581.89, Z= 2, Dc = 1.746 g/cm^3, F（000） = 598,μ（MoKa） = 1.090 mm^-1, the final R = 0.0296 and wR = 0.0806 for 3195 observed reflections with Ⅰ 〉 2σ（Ⅰ）. In the centrosymmetric compound I, each Cu（Ⅱ） ion is coordinated by six O atoms from two 5-fluorouracil-1-acetate anions and four water molecules, forming a six-coordinated octahedral environment. N-H…O and O-H…O hydrogen-bonding interactions are observed in the structure, leading to the formation of a three-dimensional network.
基金supported by the grants from the Natural science Foundation Project of Chongqing Sci & Tech Committee (CSCT, 2006BB5297)
文摘Objective： To study the combined antitumor effect and possible mechanisms of ursolic acid with 5-fluorouracil （5-FU） on human esophageal carcinoma cell Eca-109 in vitro. Methods： Eca-109 cells were treated with ursolic acid （10-50 μmol/L） and/or 5-fluorouracil （48.0-768.8 μmol/L） for 48 h in vitro. And then cell proliferation was determined by MTT assay. Cell cycle and apoptosis rate were analyzed by flow cytometry （FCM）. The morphological changes of apoptosis were observed by fluorescent microscopy. At last the expression of P27kipl, bcl-2 and bax were detected by western blot. Results： Results： In comparison with single agent treatment, the combination of ursolic acid and 5-fluorouracil produced greater efficacy in growth inhibition, cell cycle arrest at G0/G1 phase, and apoptosis induction （P〈0.05）. Western blot analysis showed that the combination use of ursolic acid and 5-fluorouracil suppressed the expression of bcl-2 and increased the expressions of bax and P27kip1. Conclusion： Ursolic acid combined with 5-fluorouracil showed adjuvant antiproliferative effects on human esophageal carcinoma cell Eca-109 in vitro, which mainly due to the induction of cell cycle arrest as well as apoptosis.
基金supported by the Foundation Study Fund of Tangshan Normal College (No.07C22)Education Committee Fund of Hebei Province (No.Z2007204,No.Z2007205)+1 种基金Application Foundation Study Fund of Tangshan City (No.06234501A-10)Science Study Fund of Tangshan Normal College (No.06D08)
文摘The geometries,electronic structure,IR spectrum and other properties of hydrogen interaction between 5-fluorouracil and glycine were studied at the B3LYP/6-31＋G＊ level.Single point energy calculations were executed at the B3LYP/6-311＋＋G＊＊ and B3LYP/aug-cc-pvdz levels,and natural bond orbital （NBO） analysis was carried out at the B3LYP/6-31＋G＊ level.Finally,the hydrogen bonds were discussed via AIM electronic density topology analysis.
文摘In order to explore whether the conventional use of 5 fluorouracil (5 Fu) had any toxic effects on trabecular meshwork cells, bovine trabecular meshwork cells were cultured in vitro and exposed to 5 Fu at different concentrations. The cellular morphology, ultrastructure, mortality and phagocytosis were studied under light microscopy, transmission electron microscopy and methods of Wright's stain. It was found that the toxic effects of 5 Fu on the cells were in a dose dependent mode. 1×10 -1 mg/ml of 5 Fu caused a large part of cells rounded up, while 1×10 -3 mg/ml of the drug only a rough appearance of the cell surface. Exposure to 1×10 -2 mg/ml of 5 Fu made mitochrone swollen and rough endoplasmic reticulum enlarged, with the cell mortality being 50.5 %. The latex microspheres engulfed in cytoplasm in cells receiving 1×10 -1 and 1×10 -2 mg/ml of 5 Fu were significantly decreased as compared with those in the control group ( P <0.01). It was concluded that the safe concentration of 5 Fu on bovine trabecular meshwork cells was 1×10 -3 mg/ml and the conventional dosage of 5 Fu in clinical practice would not cause injury to trabecular meshwork cells.
文摘AIM:There are conflicting data about p53 function on cellular sensitivity to the cytotoxic action of 5-fluorouracil (5-FU). Therefore the objective of this study was to determine the combined effects of adenovirus-mediated wild-type (wt) p53 gene transfer and 5-FU chemotherapy on pancreatic cancer cells with different p53 gene status. METHODS:Human pancreatic cancer cell lines Capan-1^(p53mut), Capan-2^(p53wt),FAMPAC^(p53mut),PANC1^(p53mut),and rat pancreatic cancer cell lines AS^(p53wt) and DSL6A^(p53null) were used for in vitro studies.Following infection with different ratios of Ad- p53-particles (MOI) in combination with 5-FU,proliferation of tumor cells and apoptosis were quantified by cell proliferation assay (WST-1) and FACS (PI-staining).In addition,DSL6A syngeneic pancreatic tumor cells were inoculated subcutaneously in to Lewis rats for in vivo studies. Tumor size,apoptosis (TUNEL) and survival were determined. RESULTS:Ad-p53 gene transfer combined with 5-FU significantly inhibited tumor cell proliferation and substantially enhanced apoptosis in all four cell lines with an alteration in the p53 gene compared to those two cell lines containing wt-p53.In vivo experiments showed the most effective tumor regression in animals treated with Ad-p53 plus 5-FU.Both in vitro and in vivo analyses revealed that a sublethal dose of Ad-p53 augmented the apoptotic response induced by 5-FU. CONCLUSION:Our results suggest that Ad-p53 may synergistically enhance 5-FU-chemosensitivity most strikingly in pancreatic cancer cells lacking p53 function.These findings illustrate that the anticancer efficacy of this combination treatment is dependent on the p53 gene status of the target tumor cells.
基金Supported by The Thailand Research Fund through The Royal Golden Jubilee PhD Program Grant No. PHD/0037/2544 for Thanasai J and Limpaiboon T and grants-in-aid from the Centre for Research and Development of Medical Diagnostic Laboratories, Faculty of Associated Medical Sciences, Khon Kaen University, Thailand, and from the Ministry of Education, Sports, Science, Culture and Technology, Japan
文摘AIM: To evaluate the role of thymidine phosphorylase (TP) in cholangiocarcinoma using small interfering RNA (siRNA). METHODS: A human cholangiocarcinoma-derived cell line KKU-M139, which has a naturally high level of endogenous TP, had TP expression transiently knocked down using siRNA. Cell growth, migration, in vitro angiogenesis, apoptosis, and cytotoxicity were assayed in TP knockdown and wild-type cell lines. RESULTS: TP mRNA and protein expression were decreased by 87.1% ± 0.49% and 72.5% ± 3.2%, respectively, compared with control cells. Inhibition of TP significantly decreased migration of KKU-M139, and suppressed migration and tube formation of human umbilical vein endothelial cells. siRNA also reduced the ability of TP to resist hypoxia-induced apoptosis, while suppression of TP reduced the sensitivity of KKU-M139 to 5-fluorouracil. CONCLUSION: Inhibition of TP may be beneficial in decreasing angiogenesis-dependent growth and migration of cholangiocarcinoma but may diminish the response to 5-fluorouracil chemotherapy.
文摘In order to improve the cancer-targeting and selective activity of antineoplastic agent [5-fluorouracil (5-FU)], a novel pH-responsive drug delivery system [pullulan acetate/sulfonamide (PA/SDM) conjugate] was syn- thesized by a diafiltration method. Sulfonamide was grafted to the hydrophobically modified pullulan acetate to enhance the pH sensitivity for better cancer-targeting delivery. 5-FU was loaded into the self-assembled nanoparti- cles by the same method. The drug-loaded self-assembled nanoparticles were successfully obtained and character- ized in terms of particle size, morphology and drug loading and release profile at various pHs. The results showed that the mean diameter of the self-assembled particles was approximately 100nm, with uniform size and good spherical morphology. The nanoparticles showed good stability at pH 7.4, which is equal to that of the normal body fluid, but shrank and aggregated below pH 6.8, which is close to the pH with tumors. The loading efficiency and concentration of released 5-FU was monitored at 269 nm on the UV/Vis spectrophotometer. The release profile was heavily pH-dependent around physiological pH, and the release rate was significantly enhanced under pH of 6.8.
基金supported by Doctoral Innovation Research Assistance Program of the Science and Technology Review (kjdb200902-11)
文摘Two novel rare earth substituted phosphotungstates containing 5-fluorouracil,K 9（C 4 H 4 FN 2 O 2） 2 Nd（PW 11 O 39） 2 ·25H 2 O（FNdPW） and K 9（C 4 H 4 FN 2 O 2） 2 Ce（PW 11 O 39） 2 ·23H 2 O（FCePW）,were synthesized and characterized by elementary analysis,FT-IR spectra,X-ray powder diffraction and 1 H NMR.The thermal analysis showed that FNdPW decomposed at 210 and 493 oC,and FCePW decomposed at 223 and 471 oC,both of which had good thermal stabilities.MTT tests were performed to study the antitumor activities against HeLa cells and HepG-2 cells of FNdPW,FCePW,5-fluorouracil,C 4 H 4 FN 2 O 2 H 2 PW 12 O 40 ·8H 2 O and K 11 Ln（PW 11 O 39） 2 ·xH 2 O（Ln=Nd,Ce）,and their cytotoxicities against HEK 293 cells.The results showed that FNdPW and FCePW possessed higher antitumor activities and lower cytotoxicities than those of 5-fluorouracil and C 4 H 4 FN 2 O 2 H 2 PW 12 O 40 ·8H 2 O,of which FNdPW exhibited the highest antitumor activates against HeLa cells（EC 50 =3.41×10-6 mol/L） and HepG-2 cells（EC 50 =6.24×10-6 mol/L）.Thus the introduction of rare earth elements and 5-fluorouracil could significantly enhance antitumor effect of polyoxometalates.
文摘Chemotherapy with continuous infusion of 5-fluorouracil and cisplatin in a monthly schedule is one of the most common regimens in the treatment of advanced gastric cancer. In this study, we evaluated the efficacy and safety of a dosedense administration of this regimen in this patient population. Sixty-six consecutive patients with previously untreated histologically confirmed unresectable or metastatic gastric adenocarcinoma were treated with a 2-hour infusion of cisplatin 100 mg/m2 followed by continuous infusion of 5-fluorouracil 1000 mg/m2/day for 5 days, every 21 days. The most common grade ≥3 toxicities were fatigue (42%), nausea/vomiting (30%) and leucopenia (12%). Four patients (6%) died from treatment-related toxicity. The response rate was 35%, the median progression-free survival was 4.3 months and the median survival was 5.9 months. In light of these results, the dose-dense approach seems to offer little, if any, benefit compared with the standard regimens.
基金support from the Fundamental Research Funds for the Central Universities(No.WY1213013ECUST)supported by Science and Technology Commission of Shanghai Municipality(STCSM,contract Nos.11DZ2260600 and 10DZ2220500)
文摘The objective of this study was to investigate the potential of methoxy polyethylene glycol（m PEG）grafted chitosan（m PEG-g-CS） to be used as a drug carrier. m PEG-g-CS was successfully synthesized by one-step method with formaldehyde. The substitution degree of m PEG on chitosan was calculated by elemental analysis and was found to be（3.23 0.25）%. m PEG-g-CS self-assembled micelles were prepared by ultrasonic method with the controlled size of 178.5–195.1 nm and spherical morphology. Stable dispersion of the micelles was formed with the zeta potential of 2.3–30.2 m V. 5-Fluorouracil（5-FU）, an anticancer chemotherapy drug, was used as a model drug to evaluate the efficiency of the new drug delivery carrier. The loading efficiency of 5-FU was（4.01 0.03）%, and the drug-loaded m PEG-g-CS self-assembled micelle showed a controlled-release effect. In summary, the m PEG-g-CS self-assembled micelle is proved to be a promising carrier with controlled particle size and controlled-release effect. Therefore, it has great potential for the application as 5-FU carriers for effective anti-tumor activity.
文摘Objective： We aimed to investigate the safety and efficiency of vinorelbine/epirubidn/fluorouracil （NEF） regimen as adjuvant chemotherapy for breast cancer. Methods： From 2005 to 2008, 227 female breast cancer patients were treated with the NEF regimen： vinorelbine 25 mg/m^2 iv on days 1 and 8; epirubicin 60 mg/m2 iv gtt on day 1; 5-Fu 500 mg/m2 iv gtt on day 1. Chemotherapy was repeated every 21-28 days for a total of 6 cycles. Results： The major side effects were neutrope- nia and gastrointestinal syndrome, with a 5-year survival rate of 85.4%, Conclusion： NEF regimen is safe and guarantees a high survival rate which could be recommended as a adjuvant chemotherapy regimen for breast cancer,
