Objective To study the effect of genistein (Gen) in combination with 5-fluorouracil (5-FU) on human gastric carcinoma cells in vitro. Methods Human gastric carcinoma cell line SGC-7901 was t reated with Gen and 5-FU alone or in combination for 24 , 48 and 72 hours , respectively. MTT assay was used to investigate the inhibitory effect of Gen and 5-FU on SGC-7901 cells. Transmission electron microscopy was used to observe the ultramicrost ructure changes of cancer cells and the flow cytometry was used to detect the distribution of cell cycle. Results Gen and 5-FU alone or in combination inhibited the proliferation of SGC-7901 cells significantly in both time-dependent and dose-dependent manner. The combination of Gen with 5-FU had synergistic effect on the growth of SGC-7901 cell line when the inhibition ratio was 20 % to 80 %. When SGC-7901 cells exposed to 18. 8μmol/ L Gen , 8. 84μmol/ L 52FU , and 3. 06μmol/ L Gen combined with 7. 96μmol/ L 5-FU for 72 hours , 62. 97 % , 63. 76 % and 67. 46 % SGC-7901 cells were arrested in G2 / M , S and G0 / G1 phrase , respectively. Gen and 5-FU could both induce apoptosis and arrest cell cycle of SGC-7901 cells. Conclusion Combination therapy of Gen with 5-FU may take synergistic inhibitory effect on the proliferation of gastric cancer cells by resting cell cycle and inducing cell apoptosis at a certain range of concent ration.
ObjectiveTo observe the effect of 5Fluorouracil(5FU) on the exocrine pancreas. MethodsThe effects of 5FU were investigated in 8 patients who had undergone pancreatoduodenectomy. The pancreatic juice was temporarily diverted to the exterior via a pancreatic duct catheter.Ten days after operation,the patients were injected intravenously with 5FU 500 mg/d for three days. The samples of pancreatic juice were taken for measurement of amylase,pH, HCO3-, Na+, K+, Cl-, Ca2+ and Mg2+.ResultsThe amylase, pH, HCO3-, Na+, K+, Cl-, Ca2+ and Mg2+ did not alteredsignificantly before and after 5FU injection.Conclusion5FU has no shortterm effect on exocrine pancreas. Therefore, improvement of acute pancreatitis cannot be achieved through inhibiting pancreatic enzymes synthesis.
ObjectiveTo investigate healing of rat colonic anastomoses after early postoperative intraperitoneal chemotherapy (EPIC).MethodsFortyfive Wistar rats with colonic anastomoses were divided randomly into 3 groups (15 rats each). From postoperative 1 day to 5 day, rats were injected with normal saline (NS) to the peritoneal cavity with 20 ml/(kg·d) for the NS group; 5Fu with 20 mg/(kg·d) for the 5Fu group; 5Fu with 20 mg/(kg·d) and leucovorin with 10 mg/(kg·d) for the 5Fu+LV group. On the 7th postoperative day, rats were killed and the anastomoses were evaluated whether anastomotic complications (leakage or dehiscence) occurred, the anastomotic bursting pressure (ABP) and hydroxypoline content (HPC) were measured. ResultsIn the NS group, 1 rat had incision dehiscence, another one had anastomostic leakage with but no death. In the 5Fu+LV group, 2 rats showed anastomotic leakage and 1 death. On the 7th postoperative day, the ABP in NS, 5Fu and 5Fu+LV groups were (169.1±32.6) mm Hg, (116.8±25.5) mm Hg and (154.9±31.2) mm Hg respectively; the HPC was (1.54±0.28) μg/mg, (0.9±0.33) μg/mg and (1.24±0.29) μg/mg respectively. Both the ABP and HPC, in the NS group were much significantly higher than in 5Fu group (P＜0.01). Both the ABP and HPC in the 5Fu+LV group were significantly higher than which in the 5Fu group (P＜0.05).ConclusionEPIC with 5Fu significantly impairs healing of the colonic anastomosis. 5Fu combined with LV for EPIC might reduce this inhibition to the process of the anastomotic healing.
Objective To evaluate the legitimate of regional artery infusion chemotherapy in the treatment of gastric carcinoma. MethodsThe pharmacokinetics of 5-Fu after different route of administration was studied. Results High concentration of 5-Fu found in portal vein via left-gastric intra-artetial administration were 4-40 folds higher than the group via intravenous administration.The time of high concentrations of 5-Fu via left-gastric intra-arterial administration maintained significantly longer than by intravenous administraion. The concentration of 5-Fu in tumor tissues and paratumorous lymph tissues by intra-arterial administration were 19 times and 23 times of the group by intravenous administration. Conclusion Regional arterial infusion chemotherapy can significantly increase the concentration of chemotherapeutic drugs in the tumorous region.
Objective To prepare the immunonanospheres［SC3Ab-HSA(5-Fu)-NS］ against human colorectal cancer and evaluate its immunoreactivity and effects on cancer. Methods SC3Ab-HSA(5-Fu)-NS was prepared by intermolecular cross-linking the monoclonal antibody SC3Ab with human serum albumin nanospheres containing 5-Fu ［HAS(5-Fu)-NS］ via new hetero-bifunctional crosslinker SPDP. Condensation test and immunoflurecence were used to evaluate the immunoreactivity, the specific binding of SC3Ab-HSA(5-Fu)-NS with colorectal cancer cell line SW1116 was observed by microscope and electron microscope. The specific cytotoxic effects on target cells were evaluated in vitro by MTT assay. SC3AbHSA(5-Fu)-NS, HSA(5-Fu)-NS and 5-Fu were injected into nude mice bearing human colorectal carcinoma, to study the inhibitory activity of SC3Ab-HSA(5-Fu)-NS in vivo. Results The immunoreactivity of SC3Ab-HSA(5-Fu)-NS was well preserved. SC3Ab-HSA(5-Fu)-NS can bind the SW1116 cells specifically. The IC50 value for SC3Ab-HSA(5-Fu)-NS on SW1116 cells was 24.6 μg/ml,which was lower than that of HSA(5-Fu)-NS(345.3 μg/ml) and 5-Fu(325.6 μg/ml). The inhibitory rate of SC3Ab-HSA(5-Fu)-NS on the growth of colorectal cancer xenografts was significantly higher than that of HSA(5-Fu)-NS or 5-Fu(P＜0.001).Conclusion SC3Ab-HSA(5-Fu)-NS has immunoreactivity and specific active targeting to the colorectal cancer cells. The anticancer ability of SC3Ab-HSA(5-Fu)-NS is significantly higher than that of HSA(5-Fu)-NS and 5-Fu.
bjectiveTo observe the effecacy of immunosuppressive agents on modulation of the disorders of inflammatory and antiinflammatory cytokines in acute pancreatitis, and to investigate the mechanism of treatment of acute pancreatitis with immunosuppressive agents. MethodsSD male rats were divided into 6 groups: group 1, the normal control group (n=6); group 2, acute pancreatitis induced by ductual injection of 5%sodium cholate sulfur at the volume of 1.0 ml/kg without treatment (n=8). After the pancreatitis were induced, the rest rats were injected intravenously with 5Fu 40 mg/kg (group 3, n=6); or methylprednisolone 30 mg/kg (group 4, n=6); or cyclophosphamide 20 mg/kg (group 5, n=6); or methotrexate 1.2 mg/kg (group 6, n=6). Twentyfour hours afteroperation, the animals were killed, the blood samples were taken for measurement of TNFα, IL1, IL6 (by bioassay), and IL10, TGFβ (by ELISA) as well as amylase. ResultsThe inflammatory cytokines (TNFα,IL1,IL6 ) and the antiinflammatory cytokines (IL10 and TGFβ), in blood of acute pancreatitis were increased significantly. After treated with immunosuppressive agents, both the inflammatory and antiinflammatory cytokines were decreased in different degrees. Some indexes of the severity of acute pancreatitis, such as amylase and pancreatic weight were improved obviously.ConclusionImmunosuppressive agents can regulate inflammatoryassociated cytokines increased remarkably in the acute pancreatitis. Therefore, improvement of acute pancreatitis can be achieved through rectifying the abnormal immunity and relieving the pathophysiological disorders of the acute pancreatitis by immunosuppressive agents.
Objective To evaluate the effect of the allied chemotherapy with 5-Fu、leucovorin (CF) and levamisole (LV) after resection of colorectal cancer. Methods 242 cases were divided randomly into three groups. 80 cases (group Ⅰ) were treated with 5-Fu and CF. 80 cases(groupⅡ) were treated with 5-Fu and LV. 82 cases (group Ⅲ) were treated with 5-Fu、CF and LV. Results The recurrence rates of group Ⅲ was 12.20%, which was significantly lower than that of group Ⅰ (26.25%) and group Ⅱ(27.50%). (P＜0.05). The 5-year survival rates in group Ⅰ, group Ⅱ and group Ⅲ were 37.50%, 35.00% and 58.54%, respectively, the highest one was in Group Ⅲ (P＜0.01). Conclusion The allied chemotherapy with 5-Fu、CF and LV is an effective therapy for petients of colorectal cancer after surgery, which can significantly decrease the recurrence and improve the 5-year survival rate.
The antitumor activity of hyperthermia combined with mitomycin(MMC),5-fluorouracil(5-Fu)was observed in human gastric carinoma cell line MGC-803.The study was aimed at understanding the percentage of living carcinoma cell,plating efficiency and survival fraction.The results showed that hyperthermia combinedwith MMC had a synergistic antitumor activity which was enhanced with temperature increasing,but it was not the same as hyperthermia combined with 5-Fu.In comparison with simple hyperthermia,the antitumor activity of hyperthermia combined with 5-Fu was enhanced at lower temperture.This results raises a basis of clinical practice.
Objective To assess the effect of basic fibroblast growth factor (bFGF) and 5-fluorouracil (5-FU) appl ied topically on the tendon adhesion and the heal ing process after the flexor tendon repair in Leghorn chickens. Methods Ninety male Leghorn chickens (weighing 3.0-3.5 kg) were randomly divided into 3 groups, with 30 chickens in each group. The flexordigitorum profundus tendons of the third right toes were transected and sutured directly. The repair site in group A was given 0.6 μL fibrin sealant (FS). In group B, the repair site was given 0.6 μL FS containing 500 ng bFGF. In group C, before the tendons were transected, they had been soaked in 5-FU solution, and then the same treatment as group B was given. Six specimens of the third toe were harvested to perform the macroscopical and histological examinations at 1, 2, 4, and 8 weeks, respectively, and to perform the biomechanical test at 8 weeks. Results All animals survived until the experiment was completed. All incisions healed smoothly. No rupture occurred in the reparied tendon. At 8 weeks, the adhesion degree was l ighter in group C than in group B (P lt; 0.05), but there was no significant difference in the adhesion degree between group A and groups B, C (P gt; 0.05). At 1, 2, and 4 weeks after operation, the number of fibroblast cells of group A was significantly less than that of group B (P lt; 0.05), and the number of fibroblast cells of group C was significantly less than that of group A and group B in the tendon sheath and epitenon (P lt; 0.05); however, it was significantly more than that of group A in the tendon parenchyma (P lt; 0.05), and no significant difference was observed when compared with that of group B (P gt; 0.05). At 8 weeks, no difference was found among 3 groups (P gt; 0.05). The collagen fiber content of group A was significantly less than that of group B at 4 and 8 weeks (P lt; 0.05). In the sheath and epitenon, the collagen fiber content of group A was significantly more than that of group C at 4 weeks (P lt; 0.05); however, no significant difference was found between 2 groups at 8 weeks (P gt; 0.05). The collagen fiber content of group A wassignificantly less than that of group C in the parenchyma at 4 and 8 weeks (P lt; 0.05). At all time points, the collagen fiber content of group B was significantly more than that of group C in the sheath and epitenon (P lt; 0.05), but no significant difference in the parenchyma was observed between 2 groups (P gt; 0.05). The biomechanical tests showed that the gl iding excursion of the tendon in groups A, B, and C was (3.51 ± 0.56), (2.84 ± 0.42), and (4.56 ± 0.59) mm, respectively; the work of flexion was (14.08 ± 1.85), (20.62 ± 3.52), and (10.91 ± 1.53) N.mm, respectively; and the ultimate tensile strength of the tendon was (11.26 ± 1.83), (15.02 ± 2.20), and (14.40 ± 1.57) N, respectively. There were significant differences in the gl iding excursion of the tendon and the work of flexion among 3 groups (P lt; 0.05) and in the ultimate tensile strength of the tendon between group A and groups B, C (P lt; 0.05), but there was no significant difference in the ultimate tensile strength of the tendon between group B and group C (P gt; 0.05). Conclusion Local single-use bFGF and 5-FU can not only effectively promote the heal ing of flexor tendon, but also significantly reduce tendon adhesion.
Objective To assess the efficacy and safety of mytomycin C versus 5-fluorouracil for trabeculectomy. Methods We electronically searched the Cochrane Central Register of Controlled Trials (Issue 3, 2008), MEDLINE (1966 to October 2008), EMbase (1947 to October 2008), CMBdisk (1979 to October 2008).We also handsearched relevant conference proceedings. Data were extracted by two reviewers independently using an extraction form. The Cochrane Collaboration’ s RevMan 5.0 software was used for statistical analyses. Results Nine randomized controlled trials (RCTs) involving 482 participants (495eyes) were identified. The trials enrolled three types of participants (high risk of failure, moderate risk of failure, low risk of failure). As for high risk of failure, compared with mytomycin C, 5-fluorouracil appeared to increase the rate of postoperative complications (RR –5.74, 95%CI –9.91, –1.58). No significant differences were found in postoperative mean intraocular pressure(IOP) (WMD –?2.31, 95%CI –?7.34, 2.71), success rate (RR 1.13, 95%CI 0.91, 1.39) and visual acuity ≥3-line decrease (RR 1.46, 95%CI 0.43, 4.94). As for low risk of failure, there were no significant differences in success rate (RR 1.10, 95%CI 0.99, 1.22) and postoperative complications (RR 1.00, 95%CI –6.21, 8.21). Conclusion In both groups of high risk and low risk of failure, there are no significant differences in postoperative mean IOP and success rate. However, in the group of high risk of failure, compared with 5-fluorouracil, mytomycin C appears to raise the rate of postoperative complications; the rate of reducing the eyes pressure cannot be concluded based on current evidence. However, as the number of the studied cases is rather small and the period of observation is also limited, long-term follow-up of multi-central RCTs with a larger number of cases are still needed before definite conclusions can be made. Further studies are also needed to better determine the pharmacokinetics and cost-effective analyses involving the use of the two agents for glaucoma filtering surgery.