Objective To assess an effect of 5-fluorouracil (5-FU) applied topically on the tendon adhesion and the healing process after the flexor tendon repair in Leghorn chickens. Methods Thirtytwo white Leghorn chickens, aged 4 months and weighing 1.5-1.7 kg, were randomly divided into 2 groups: Group A andGroup B, with 16 chickens in each group. The flexor digitorum profundus tendons of the 2nd, 3rd and 4th toes were transected and repaired. The repair site in Group A was given 5-FU in a concentration of 25 mg/ml with a soaked sponge that wascut into pieces 7 mm×20 mm×1 mm in size, and the synovial sheath of the repair site was wrapped with the 5-FU-soaked sponge for 1 min for 4 times. The repair site in Group B was served as a control, with no 5-FU but with the sterile normal saline. At 3 and 6 weeks postoperatively, the repaired tendons and the tendon adhesion formation were examined macroscopically and histologically，and the repaired tendons were tested biomechanically. The tissue blocks from the tendon repair site were examined under the transmission electron microscope. Results At 3 and 6 weeks postoperatively, the macroscopic and histological observation showed that the peritendinous adhesions in Group A were looser when compared with those in Group B. The length of the tendon gliding and the extent of yieldance to exercise were found to be 4.85±1.31 mm, 0.67±0.42 mm and 5.74±1.61 mm, 1.55±0.35 mm respectively at 3 and 6 weeks after operation in Group A，but 2.99±0.51mm，0.24±0.14 mm and 3.65±0.54 mm, 1.22±0.16 mm in Group B.Group A was significantly greater in the abovementioned parameters than Group B (P＜0.05).At 3 weeks after operation, the ultimate breaking strength was 20.28±4.92 N in Group A and 21.29±4.88 N in Group B, with no statistically significant difference found between the two groups (P＞0.05). At 6 weeks, the ultimate breaking strength was 47.12±6.76 N in Group A but 39.31±7.20 N in Group B, with a significant difference between the two groups (P＜0.05). Conclusion 5-fuorouracil, when appliedtopically, can reduce the tendon adhesion, with no inhibition of the intrinsic healing mechanism. It is an ideal treatment strategy to prevent peritendinous adhesion.
ObjectiveTo investigate the effects of dipyridamole (DP), one of the human equilibrative nucleoside transporters (hENTs) blockers, on 5-fluorouracil (5-FU) induced cell apoptosis and cell cycle changes of the pancreatic cancer Panc-1 cell line. MethodsPancreatic cancer cell line Panc-1 was divided into hENTs blocked group and hENTs unblocked group. The hENTs blocked group was further divided into two subgroups according to the DP concentration, 5 μmol/L DP group and 10 μmol/L DP group. Each group was incubated in culture medium with or without 1.5×106 ng/L 5-FU for 24 h. Cell apoptosis and cell cycle were detected by flow cytometry. Results①The apoptosis results of each group： Incubated in culture medium with 1.5×106 ng/L 5-FU for 24 h, the apoptosis rates of 5 μmol/L DP group and 10 μmol/L DP group were higer than those of hENTs unblocked group （Plt;0.05）, and which of 10 μmol/L DP group was higer than that of 5 μmol/L DP group (Plt;0.05). Incubated in culture medium without 5-FU for 24 h, there were no significant differences of the apoptosis rates among three groups (Pgt;0.05). ②The cell cycle results of each group: Incubated in culture medium with 1.5×106 ng/L 5-FU for 24 h, the percentages of S phase cells in the 5 μmol/L DP group and 10 μmol/L DP group were less than those of hENTs unblocked group (Plt;0.05). The percentage of S phase cell of 5 μmol/L DP group reduced to 87.09% and that of 10 μmol/L DP group reduced to 74.06% as compared with hENTs unblocked group. 5-FU had little influence on G2 phase (Pgt;0.05) except for the percentage of G2 phase cells in the 5 μmol/L DP group increased significantly (Plt;0.05) as compared with the hENTs unblocked group. Incubated in culture medium without 5-FU for 24 h, there were no significant differences of the cell cycles among three groups (Pgt;0.05). ConclusionsIn pancreatic cancer Panc-1 cell, DP could enhance the cytotoxicity of 5-FU by blocking hENTs. The enhanced cytotoxicity is related to elevation of 5-FU concentration in cells, and unrelated to DP itself.
ObjectiveTo detect 5-FU concentration and investigate the changes of pathology， and Ki-67 protein expression after intraoperative regional chemotherapy (RC) for colon cancer. MethodsAll the patients were randomized into two groups: RC group (n=20), received intraoperational RC with 100 ml physiological saline contained 5-FU (15 mg/kg) and camptothecine (0.06 mg/kg)； control group (n=20), saline alone. The samples from portal vein blood, peripheral blood, peritoneal fluid， and peri-cancerous tissues in RC group were taken to detect the 5-FU concentration by high performance liquid chromatography (HPLC), respectively at 2, 5, 10, 20, 30, and 60 minutes after treatment. The pathological changes were observed and Ki-67 protein expressions were examined by immunohistochemical staining for all the cancer tissues postoperatively in two groups. ResultsPeak concentration of 5-FU appeared at 2 min after treatment, and decreased gradually. 5-FU concentration in peritoneal fluid was the highest, and the lowest in the peripheral blood (Plt;0.01). In RC group， light karyopyknosis, nuclear swelling, and coagulative necrosis of cancer cells, and light intercellular substance hydropsia, inflammatory cells invasion were observed under light microscopic examination; light vasculitis presented also in five cases. Nuclear swelling, heterochromatin agglutination, perinuclear gap expansion, mitochondrial swelling, endoplasmic reticulum expansion, and Golgi complex expansion were observed with transmission electron microscope. Ki-67 protein expression of colon cance tissues in RC group was lower than that in control group （Plt;0.05）. Conclusions Intraoperative RC for colon cancer may sustain a high concentration of chemotherapy drugs in peritoneal fluid and portal vein blood, and alter histopathological morphology of cancer cells, and suppress Ki-67 protein expression. So, intraoperative RC may play an important role in preventing intraoperative spreading and postoperative recurrence of colon cancer.
ObjectiveTo investigate the effect of expressions of nucleoside transporters subtype (hENT1 and hENT2) on 5-fluorouracil(5-FU) cytotoxicity in breast cancer cell lines(MDA-MB-231, MDA-MB-468, SK-BR-3, MCF-7). MethodsFour breast cancer cell lines were chosen to detect the mRNA expressions of hENT1 and hENT2 by RT-PCR. Cells were incubated in the medium with a serial concentrations of 5-FU from 1.28×104 ng/L to 2.00×108 ng/L for 48 h. Then the cell proliferation in each cell line was measured by MTT assay and the IC50 was evaluated. Results①The mRNA expressions of hENT1 and hENT2 in the MDA-MB-231, MDA-MB-468, or SK-BR-3 cells were significantly higher than thoes in the MCF-7 cells(P < 0.05). The mRNA expression of hENT2 was detected in the MDA-MB-231, MDA-MB-468, or SK-BR-3 cells, not detected in the MCF-7 cells. 2MTT showed that IC50 of 5-FU in the MDAMB-231, MDA-MB-468, or SK-BR-3 cells was significantly lower than that in the MCF-7 cells(P < 0.05). There was no statistical difference of IC50 among the three lines(MDA-MB-231, MDA-MB-468, and SK-BR-3)(P > 0.05).③The three lines(MDA-MB-231, MDA-MB-468, and SK-BR-3) with lower IC50 of 5-FU highly expressed hENTs, and MCF-7 cell with the higher IC50 of 5-FU expressed less hENTs. ConclusionsThe expressions of hENTs in breast cancer cell lines can significantly influence 5-FU cytotoxic effect. It is implicated that the hENTs expressions might be the clue to the choice of nucleoside anticancer drugs in clinic.
Objective To investigate the effect of imbedding chemotherapy of sustained release of 5-fluorouracil on the healing of colonic stoma in dog. Methods Twenty-eight adult hybrid dogs were randomly divided into chemotherapy group （n=22) and control group (n=6). The canine sigmoid colon were firstly detached and then anastomosed via median abdominal incision, 200 mg sustained release of 5-fluorouracil was imbedded in the mesentery 1.0-1.5 cm away from colonic stoma in chemotherapy group, whereas the control substance was injected into the dogs in control group. Tissue samples were collected from mesentery and stomas on 3, 5, 7, 10 and 15 days after operation, respectively, in order to observe the healing of stoma. The drug concentrations in the stoma and in the tissues that were 0, 1, 3, 5, 7, 10 and 15 cm away from the imbedding point were also measured by high performance liquid chromatographymethod at different phases. Results The tissues from colonic stoma only showed inflammatory reaction at early stage, with no necrosis and cellular degeneration. It was observed that the stoma healed basically on the tenth day after operation. The drug concentrations in the tissues gradually decreased at the range of 0-15 cm over time, but all of which were higher than the anti-tumor effective concentration （0.10 μg/g）. Conclusion The imbedding chemotherapy of sustained release of 5-fluorouracil in mesentery has little effect on the healing of stoma, and it could remain an effective anti-tumor concentration in a period of time.
Objective To explore the effect on apoptotic genes of pancreatic adenocarcinoma cell BxPC-3 from subcutaneous transplantation tumor in nude mice induced by 5-FU and sulfasalazine (SZ).Methods Changes of apoptosis-related genes 〔bcl-2, cyclinD1, Bax and NF-κB (p65)〕 in subcutaneous transplantation tumor treated by 5-FU, SZ alone or both at the levels of mRNA and protein were measured by RT-PCR and Western blot. Results NF-κB (p65) at mRNA relative content and protein expression in subcutaneously heterotopic transplantation tumor treated by 5-FU (7.5, 15 mg/kg), SZ (10, 20 mg/kg) alone or both showed significant difference, except for two subsets in SZ group, respectively, in comparison with each control group (P＜0.01). Meanwhile bcl-2 and cyclinD1 at the levels of mRNA and protein, and Bax protein level were significantly different from each control group (P＜0.01). The above-mentioned indexes were show obvious interaction of both by multiple factor analysis of variance. Conclusion Up-regulated level of Bax, down-regulated levels of bcl-2, cyclinD1 and NF-κB (p65) might be one of apoptotic mechanisms that SZ synergistically enhanced apoptotic effect on pancreatic adenocarcinoma cell BxPC-3 of subcutaneous transplantation tumor in nude mice induced by 5-FU.
目的 探讨术中应用缓释5-氟尿嘧啶在结直肠癌治疗中的价值及安全性。方法 回顾性分析173例结直肠癌患者术中应用缓释5-氟尿嘧啶后的疗效和不良反应。结果 171例患者顺利出院，1例患者死于严重骨髓抑制，1例死于真菌败血症； 无出血、吻合口漏、肠穿孔、肠梗阻等严重并发症发生。155例患者获6个月至3年的随访，随访期间死亡23例，发生局部复发5例，肝脏等远处转移3例。结论 结直肠癌术中使用缓释5-氟尿嘧啶是安全、有效的。
Objective To study the inhibitive effect of adenovirus mediated CD gene and 5-FC on proliferative human retinal pigment epithelial (HRPE) cells, and to search for an effective method to take precautions against proliferative vitroretinopathy (PVR).Method Different concentrations of CD and 5-FC were added respectively to the cultured third-growth-generation HRPE cells.Transferance rate was detected by positive HRPE cells marked by X-gal and LacZ. The number of HRPE cells were counted and evaluated by methylthiazol-tetrazollium (MTT) method. Results The adenovirus mediated CD gene could be transfered into HRPE cells with a dose-dependent manner. Positive HRPE cells with CD gene could transform 5-FC to 5-Fu,which could inhibit the increase of HRPE cells effectively. No obvious bystander effect on the growth of HRPE cells was detected.Conclusions The adenovirus may introduce a foreign gene into cultured HRPE cells efficiently. It could be a good method to treat and prevent PVR by medication. (Chin J Ocul Fundus Dis，2003，19：168-171)
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.
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.