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.
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.
To evaluate the effect of 5-fluorouracil (5-FU) appl ied topically on preventing adhesion andpromoting functional recovery after tendon repair. Methods From August 2003 to June 2007, 48 patients with flexor tendonrupture of the fingers by sharp instrument were treated and randomly divided into two groups. In 5-FU group, 39 fingers of 26 patients included 17 males and 9 females, aged (29.3 ± 9.8) years; the locations were zone I in 19 fingers and zone II in 20 fingers; single finger was involved in 12 cases and more than 2 fingers were involved in 14 cases; and the time from injury to operation was (2.4 ± 1.6) hours. In control group, 36 fingers of 22 patients included 14 males and 8 females; aged (26.1 ± 8.7) years; the locations were zone I in 16 fingers and zone II in 20 fingers; single finger was involved in 10 cases and more than 2 fingers were involved in 12 cases; and the time from injury to operation was (2.1 ± 1.8) hours. No statistically significant difference was found in constituent ratio of age, gender, injured fingers and their zones, between two groups (P gt; 0.05). The repair site in 5-FU group was given 5-FU at a concentration of 25 mg/mL with a soaked sponge, and the synovial sheath of the repaired site was wrapped with the 5-FU-soaked sponge for 1 minute for 4 times after the tendons were repaired; normal sal ine was used in the control group. Results Wound healed by first intention and no infection and tendon rupture occurred in two groups. The patients were followed up for 3-8 months (mean 4.1 months) and 3-8 months (mean 3.9 months) in 5-FU group and in control group respectively. The functional recovery degrees of the fingers were evaluated with total active movement (TAM) evaluation system. In 5-FU group, the results were excellent in 22 fingers, good in 13 fingers, fair in 3 fingers and poor in 1 finger; the excellentand good rate was 89.7%. In control group, the results were excellent in 11 fingers, good in 15 fingers, fair in 9 fingers andpoor in 1 finger; the excellent and good rate was 72.2%. There was statistically significant difference in the functional recovery degrees of fingers between two groups (P lt; 0.05). The 2 fingers which had a poor result in 5-FU group and control group were served with tenolysis was performed in 2 cases having poor results after 6 months of operation and had an excellent result at last. Conclusion 5-FU appl ied topically can reduce tendon adhesions after the ruptured tendon repair.
目的觀察直腸癌術中局部植入氟尿嘧啶緩釋劑（5-FU SRI）的可行性及療效。 方法92例直腸癌患者分成治療組和對照組，治療組術中在瘤床和沿淋巴引流途徑分多點植入5-FU SRI 600 mg，對照組行常規直腸癌根治術，觀察2組患者的手術情況、毒副反應、近期并發癥及遠期療效。 結果2組的手術時間、出血量以及腹膜炎、吻合口漏、腸梗阻和切口感染發生率的差異均無統計學意義（P＞0.05）；2組患者的白細胞計數、肌酐及ALT水平治療后高于治療前（P＜0.05），但2組間差異無統計學意義（P＞0.05）。治療組腹腔局部復發率及遠處轉移率均較對照組低（P＜0.05）。 結論直腸癌術中植入5-FU SRI是安全可行的，是預防術后復發轉移的有效途徑。
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 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.
ObjectiveTo investigate the lymphatic targeting of 5-fluorouracil (5-FU) carbon nanoparticles in rats. Methods5-FU concentration in lymphoid tissue of rats was determined by reversed phase high performance liquid chromatography after intraperitoneal injection of 5-FU carbon nanoparticle and 5-FU ordinary form (20 mg/kg body weight). Results5-FU concentration of lymphoid tissue in the 5-FU carbon nanoparticle group was higher than that in the 5-FU ordinary form group, and could sustain a longer time. Conclusion5-FU carbon nanoparticles injection can improve the drug concentration of target lymphatic organs, also has a good lymphatic targeting
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 value of different minimally invasive surgical techniques, stent placement, laparoscopic surgery, and sustained-releasing 5-fluorouracil, in solving intestinal obstruction due to colorectal cancer. MethodsFrom May 2000 to May 2010, total 68 patients with obstructed colorectal cancers in three centers were treated in two ways in terms of the stage: The first, patients with resectable tumors underwent colorectal stent placement as a ‘bridge to surgery’ guided by enteroscope under X-ray. After clinical decompression and bowel preparation, laparoscopic radical resection was performed. The second, patients with unresectable tumors underwent rectal stent placement just for palliation. Sustained-releasing 5-fluorouracil was implanted into the local cancerous intestinal tract through stent walls. ResultsFifty-one of 52 patients underwent laparoscopic radical resection successfully following stent placement, while one failed and died during follow-up 93 d postoperatively. Forty patients with successful laparoscopic surgery were followed up in 3 to 36 months (with an average of 15 months) without tumor planting in the incision, postoperative local recurrence or anastomotic stricture. Fifteen unresectable patients and one high-risk, intolerable patient underwent rectal stent placement and implantation of sustained-releasing 5fluorouracil. During follow-up 3 to 24 months (with an average of 14 months), 11 died, who survived for (350±222) d (range 101-720 d), and 5 were still alive for 3 to 13 months (with an average of 9 months) without intestinal obstruction. ConclusionsLaparoscopic surgery combined with stent placement is an effective and safe procedure for resectable obstructed colorectal cancer. For unresectal obstructed rectal cancer, rectal stent placement combined with sustained-releasing 5-fluorouracil can prolong survival time avoiding colostomy.
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.