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 evaluate the efficacy and safety of intraoperative mesenchymal chemotherapy with 5-FU implants in radical gastrectomy of advanced gastric cancer. Methods From January 2008 to September 2009， 102 patients with historically proven advanced gastric cancer were enrolled in our department and were allocated to undergo either radical gastrectomy and intraoperative mesenchymal chemotherapy with 5-FU implants 800 mg（treatment group， n=51）， or radical gastrectomy alone （control group， n=51）. The postoperative complications and recurrence rate between two groups were compared. Results There were no significant differences on the volume of abdominal cavity drainage， count of white blood cells， albumin level， and gastrointestinal adverse events between the two groups （P＞0.05）. After a median follow-up of 28 months， the local recurrence rate was lower among patients in treatment group than that in control group （16.3% vs. 39.1%， P＜0.05）， the survival rate of 3-year was higher in treatment group than that in control group （85.8% vs. 67.3%， P＜0.05）. Conclusions Compared with the control group， there are no significant adverse reactions on patients with advanced gastric cancer who were implanted fluorouraci1 implants during operation， which can reduce local recurrence rates and improve the survival rates.
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 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.
Objective To explore the effects of intraperitoneal chemotherapy with fluorouracil (FU) on the growth and metastasis of tumor cells in carbon dioxide (CO2) pneumoperitoneum. Methods Fifty male H-22 mice of clean grade were selected and randomly assigned into 5 groups in each group with 10: simple implantation group, pneumoperitoneum group, pneumoperitoneum and NS group, pneumoperitoneum and low concentration (5.0 g/L) of FU group and pneumoperitoneum and high concentration (10.0 g/L) of FU group. All mice were executed after 11 days to observe the weight and the implantation of tumor in abdominal wall. Then the expressions of proliferating cell nuclear antigen (PCNA) and vascular endothelial growth factor (VEGF) were detected by immunohistochemistry. Results The tumor weight was significantly higher in pneumoperitoneum and high concentration of FU group compared with other groups except pneumoperitoneum and low concentration of FU group (P＜0.05, P＜0.01 ). The inhibition rate of tumor was 64.5% in pneumoperitoneum and high concentration of FU group. The diameter of portsite implantation nodus was significantly bigger in pneumoperitoneum and NS group compared with pneumoperitoneum and low concentration of FU group and pneumoperitoneum and high concentration of FU group (P＜0.01). The expressions of PCNA and VEGF of ascites and portsite implantation nodus were significantly different in every group, respectively (P＜0.05, P＜0.01). Conclusion There is inhibitive effect of intraperitoneal chemotherapy with high concentration of FU on the growth and metastasis of S-180 tumor cells in CO2 pneumoperitoneum, which may be associated with downregulation of PCNA and VEGF expressions.
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 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.
ObjectiveTo assess the effectiveness and safety of capacitance combined with irinotecan (CAPIRI) versus fluorouracil combined with irinotecan (FOLFIRI) for patients with advanced metastatic colorectal cancer. MethodsDatabases such as Pubmed, Embase, Wanfang data, CNKI, Cochran Library were searched from January 2000 to October 2015. We evaluated the quality of randomized controlled trials (RCTs) and then extracted data from them. RevMan 5.2 software was used to perform the meta-analysis. ResultsEight RCTs studies with 1 634 advanced metastatic colorectal cancer patients were included based on our standard. CAPIRI regimen was equal to FOLFIRI regimen in complete response rate [RR=1.17, 95%CI (0.70, 1.96), P=0.56], overall respond rate [RR=0.90, 95%CI (0.79, 1.03), P=0.12], disease control rate [RR=0.93, 95%CI (0.87, 1.00), P=0.06], median progression-free survival [HR=1.00, 95%CI (0.72, 1.37), P=0.99], and median overall survival [HR=0.94, 95%CI (0.63, 1.40), P=0.77]. For safety, higher incidence rate of grade 3/4 vomiting [RR=1.91, 95%CI (1.13, 3.22), P=0.02], diarrhea [RR=2.84, 95%CI (2.22, 3.63), P<0.000 01], hand-foot syndrome [RR=4.55, 95%CI (2.15, 9.61), P<0.000 1] were confirmed for CAPIRI. The two methods had similar toxicities: nausea [RR=0.77, 95%CI (0.64, 0.93), P=0.005], fatigue [RR=1.19, 95%CI (0.73, 1.94), P=0.47], febrile neutropenia [RR=1.59, 95%CI (0.89, 2.87), P=0.12], anemia [RR=1.74, 95%CI (0.59, 5.18), P=0.32], and leukopenia [RR=0.77, 95%CI (0.64, 0.93), P=0.005]. ConclusionCapecitabine combined with irinotecan treatment for advanced colorectal cancer is effective and its toxicity is acceptable.
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 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.