Objective To investigate the influence of cationic liposomemediated endostatin gene on colorectal cancer liver metastasis. Methods Animal model for colorectal carcinoma liver metastasis were established. The plasmid expressing endostatin genelipofectAMINE were injected in vein. Results After cationic liposomemediated endostatin gene were injected in vein, the incidence of liver metastasis and mean numbers of liver tumors were decreased, survival time of animal was significantly longer. Conclusion Intravenous injection of cationic liposomemediated endostatin gene can control the development of colorectal cancer liver metastasis effectively.
Liposome is an ideal drug carrier with many advantages such as excellent biocompatibility, non-immunogenicity, and easy functionalization, and has been used for the clinical treatment of many diseases including tumors. For the treatment of tumors, liposome has some passive targeting capability, but the passive targeting effect alone is very limited in improving the drug enrichment in tumor tissues, and active targeting is an effective strategy to improve the drug enrichment. Therefore, active targeting liposome drug-carriers have been extensively studied for decades. In this paper, we review the research progresses on active targeting liposome drug-carriers based on the specific binding of the carriers to the surface of tumor cells, and summarize the opportunities, challenges and future prospects in this field.
【Abstract】 Objective To investigate the anti-infection and bone repair effects of cationic l i posome-encapsulatedvancomycin combined with the nano-hydroxyapatite/chitosan/konjac glucomannan (n-HA/CS/KGM) composite scaffold invivo. Methods Fifty-one 6-month-old New Zealand white rabbits, weighing 1.5-3.0 kg, were selected to prepare chronicinfectious tibia bone defect model by using Staphylococcus aureus. After 4 weeks, 48 survival rabbits were randomly divided into 4 groups (n=12). After debridement, defect was treated with nothing in group A, with n-HA/CS/KGM composite scaffold in group B, with vancomycin and n-HA/CS/KGM composite scaffold in group C, and with cationic l i posome-encapsulated vancomycin and n-HA/CS/KGM composite scaffold in group D. After 8 weeks of treatment, general observation, X-ray, HE staining, the bacterial culture, and the measurement of the longest diameter of bone defect were done. Results At 4 weeks after modeling, 48 rabbits were diagnosed as having osteomyelitis, including periosteal new bone formation, destruction of bone, and soft tissue swell ing. The Norden score was 3.83 ± 0.52. At 8 weeks after treatment, sinus healed in groups C and D, but sinus was observed in groups A and B; the gross bone pathologieal scores of group D were significantly better than those of groups A and B (P lt; 0.05). Bone defects were repaired completely in group D, the results of the longest diameter of bone defects in group D was significantly better than those in the other 3 groups (P lt; 0.05). New bone formation was observed in groups C and D, but periosteal reactionand marrow low-density shadow were observed in groups A and B; Norden score in group D was significantly better than those in groups A, B, and C (P lt; 0.05). HE staining showed that there were a large number of trabecular bone formation and fibrosis, with no obvious signs of infection in groups C and D, but neutrophil accumulation was observed in groups A and B; Smeltzer scores in groups C and D were significantly better than those in groups A and B (P lt; 0.05). Bacteriological results showed higher negative rate in groups C and D than in groups A and B (P lt; 0.05). Conclusion Cationic l iposome-encapsulated vancomycin and n-HA/CS/KGM composite scaffold can be a good treatment for infectious bone defects in rabbits, providing a new strategy for the therapy of bone defects in chronic infection.
【Abstract】ObjectiveTo construct a recombinant eukaryotic expression vector for human endostatin in order to study the inhibitory effect of liposome-mediated endostatin gene on the growth of human liver carcinoma in nude mice. MethodsHuman endostatin cDNA including IL-2 secreting peptide was cloned into eukaryotic expression plasmid pcDNA3.0 to construct recombinant plasmid pCD-sEndo. pCD-sEndo plasmid was transferred into hepatocarcinoma cell line SMMC-7721 mediated by liposome Dosper, the expression and secretion of endostatin gene was detected by RTPCR and Western blot analysis. The suspension of SMMC-7721 cells was injected subcutaneously at the back of 32 nude mice to establish the model of human liver carcinoma. The mice were divided into 4 groups randomly, and injected with Dosper+pCD-sEndo, Dosper+pcDNA3.0, Dosper and physiological brine separately. Tumor volume was measured by stages. The mice were executed after the drug had been given for 1 week, then the microvessel density (MVD) of the tumor tissue was detected with immunohistochemical method and apoptotic index of tumor cells was measured by TUNEL-stain. ResultsThe eukaryotic expression vector pCD-sEndo was successfully constructed and was confirmed by enzyme digestion and sequence analysis. Expression of endostatin gene was detected in transfected SMMS-7721 cells by RTPCR in vitro, and endostatin protein was also detected in the supernatant of transfected SMMS-7721 cells by Western blot. In vivo study, the growth of human liver carcinoma was inhibited in the group injected with endostatin gene: the average volume of tumor in this group was significantly smaller than that in other groups （P＜0.05）; the average MVD in this group was 6.2±2.5, significantly less than that in the group injected with physiological brine (32.8±6.4), Dosper （27.8±6.4）, or Dosper+pcDNA3.0 (25.5±5.5), P＜0.05. The average apoptotic index of tumor cells in treatment group, brine group, Dosper group and Desper+pcDNA3.0 group was 24.5±7.3, 7.6±2.5, 9.5±3.0 and 11.2±3.6 respectively, it was evidently higher in the treatment group than in the latter three groups. ConclusionHuman endostatin mediated by cation liposome could decrease the microvessel number of implanted human hepatocarcinoma in nude mice. It could also accelerate apoptosis of tumor cells and inhibit growth of tumor.
【Abstract】ObjectiveTo investigate the effect of genetic modulation of the hepatic graft with IL-10 during liver preservation in rat liver transplantation. MethodsEleven cases of orthotopic liver transplantation were performed in Lewis to BN rats according to the cuff’s technique. All rats were divided into 3 groups,which were control group(n=3), Lipo group(n=4) and Lipo-rIL-10 group(n=4). Lipofectamine 2000-pCR3.1 complex and Lipofectamine 2000-pCR3.1 rIL10 complex were respectively injected into portal vein and kept for 45 minutes to transfect grafts during cold preservation in vitro. All rats were killed on postoperative day 6. Serum samples were collected for decting IL-10 by means ELISA. Transgene expression of rIL-10 was assessed by means of RT-PCR and immunohistochemistry. ResultsIn Lipo-rIL-10 group, levels of IL-10 from suprahepatic vena cava were significant higher than those from infrahepatic vena cava (P=0.024), transgene expression of rIL-10 in Lipo-rIL-10 were higher than those of control group and Lipo group assessed by means of RT-PCR and immunohistochemistry. ConclusionDuring cold preservation in vitro through portal vein injection to donor liver, liposome mediated gene transfection can successfully achieve local gene expression.
OBJECTIVE: To study the therapeutic effect of Suyuping in which liposome is the main constituent on II degree burn wound. METHODS: From October 1998 to October 1999, 42 cases with II degree burn wound were adopted in this study. Among them, there were 30 males and 12 females, the average wound area was (23.4 +/- 9.7)%. The wounds on the left side of body were managed with sulfadiazine argentum(SD-Ag) while that on the right side with Suyuping. Healing and other situation about the burn wounds were observed and recorded at times. RESULTS: Forty-two patients completely healed when discharged from hospital. The average wound area managed with Suyuping was (11.2 +/- 7.3)% and the area with SD-Ag was (9.4 +/- 5.8)%. The mean healing time of Suyuping group was(18.4 +/- 4.7) days while that of SD-Ag was (23.5 +/- 7.9) days, there was significant difference(P lt; 0.05). Suyuping group presented few wound pain, allergy, bleeding and the side effect was less. CONCLUSION: Suyuping can accelerate wound healing and attenuate wound pain, allergy and bleeding, it is a potential and specific topical agent for treating II degree burn wound.
Objective To assess the clinical efficacy, safety and cost-effectiveness of topotecan for recurrent epithelial ovarian cancer. Methods We searched MEDLINE (1966 to 2005), EMbase (1989 to 2004), CancerLit (1996 to 2003), CBMdisc (1978 to 2005), CNKI (1994 to 2005), The Cochrane Library (Issue 3, 2005), The National Research Register, and the Health Technology Assessment Database (HTA). Relevant journals were also handsearched. The search was conducted on December 31, 2005. Randomize controlled trials (RCTs) comparing topotecan versus other agents for recurrent epithelial ovarian cancer were included. The quality of the eligible trials was assessed by two reviewers independently. Meta-analysis was performed. Results Four RCTs met the inclusion criteria, and the methodological quality was either level A or B. When used as second-line chemotherapy for recurrent ovarian cancer, there was no significant difference in remission rate between topotecan and paclitaxel or pegylated liposomal doxorubicin (PLD). The clinical benefit rate of topotecan was higher than that of paclitaxel or PLD. Myelosuppression was more frequent in patients in the topotecan group than those in the PLD or paclitaxel group, but it was not severe. As to cost-effectiveness analysis, topotecan was better than PLD. Conclusions The standard regimen of topotecan (intravenous 1.5 mg/m2/d for 5 consecutive days) is recommended for use in platinum-resistant and refractory ovarian cancer.
ObjectiveTo evaluate the therapeutic effect and adverse reaction of paclitaxel liposome combined with continuous infusion of large-dose 5-fluorouracil(5-fu) in treatment for advance gastric cancer(AGC). MethodsFrom May 2009 to August 2012, 63 consecutive patients with AGC in this hospital were enrolled in this study. All the patients were given chemotherapy including paclitaxel liposome and continuous infusion of large-dose(2.5 g/m2) 5-fu. The efficacy and toxicity of this regimen were observed. ResultsThere was no patient who could not tolerate adverse reaction related to such regimen. Five cases achieved complete response and 31 cases achieved partial response, the overall response rate was 57.1%(36/63). Hematologic toxicity included gradeⅢ/Ⅳleucopenia 8 cases(12.7%) and neutropenia 10 cases(15.9%), while there was no occurrence of gradeⅢ/Ⅳanemia or thrombopenia. Non-hematologic toxicity was fairly mild. ConclusionsPaclitaxel liposome is safe, well tolerated, highly targeted, and has long duration of effect. Paclitaxel liposome combined with continuous infusion of large-dose 5-fu is safe and effective in treatment for patients with AGC.
Microvesicles (MVs) is small membrane vesicles released from different cell types under different conditions. Studies have shown that MVs may mediate vascular inflammation, angiogenesis, and other pathological processes. MVs may play an important role in the pathogenesis of diabetic retinopathy (DR) by mediating endothelial cell injury, thrombosis and neovascularization. The plasma MV level may be an effective parameter to monitor the development of DR. This article will summarize the research progress of the relationship between MVs and DR in recent years.