Inhibitory effect of humanized anti-VEGFR-2 ScFv-As2O3-stealth nanoparticles conjugate on growth of human hepatocellular carcinoma: in vitro and in vivo studies

OBJECTIVE@#To investigate the inhibitory effect of humanized anti-VEGFR-2 ScFv-As2O3-stealth nanoparticles conjugate on growth of human hepatocellular carcinoma both in vitro and in vivo, which may be a potential agents with sensitivity and targeting ability for human hepatocellular cancer.@*METHODS@#Humanized anti-VEGFR-2 ScFv-As2O3-stealth nanoparticles conjugate was previously constructed using ribosome display technology and antibody conjugate technology. In this combined in vitro and in vivo study, the inhibitory effects of anti-VEGFR-2 ScFv-As2O3-stealth nanoparticles conjugate on tumor growth, invasion, and metastasis was observed with human liver carcinoma cell line Bel7402 and normal cell L02 by MTT assay, Tanswell assay, Hochest33258 staining, and DNA ladder analysis. The anticancer activity and distribution of anti-VEGFR-2 ScFv-As2O3-stealth nanoparticles was then verified in a mouse model of Bel7402 xenografts.@*RESULTS@#Anti-VEGFR-2 ScFv-As2O3-stealth nanoparticles significantly inhibited the proliferation of Bel7402 in the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay while had almost no effects on L02 cells. And the apoptosis inducing effects were proved by Hochest33258 staining and DNA ladder analysis. Transwell assay found that the drug also inhibited the metastasis ability of tumor cells. Furthermore, anti-VEGFR-2 ScFv-As2O3-stealth nanoparticles significantly delayed the growth of Bel7402 xenografts after administration (92.9%), followed by As2O3-stealth nanoparticles, anti-VEGFR-2 ScFv, and As2O3 (61.4%, 58.8%, 20.5%, P<0.05). The concentration of As2O3 in anti-VEGFR-2 ScFv-As2O3-stealth nanoparticles group was more selectively.@*CONCLUSIONS@#Anti-VEGFR-2 ScFv-As2O3-stealth nanoparticles is a potent and selective anti-hepatocellular carcinoma agent which could inhibit the growth of liver cancer as a targeting agent both in vitro and in vivo and also significantly inhibit angiogenesis.

Roles of targeting Ras/Raf/MEK/ERK signaling pathways in the treatment of esophageal carcinoma / 药学学报

Ras is best known for its ability to regulate cell growth, proliferation and differentiation. Mutations in Ras are associated with the abnormal cell proliferation which can result in incidence of all human cancers. Extracellular signal-regulated kinase (ERK) is a downstream effector of Ras and plays important roles in prognosis of tumors. Recently, evidence has gradually accumulated to demonstrate that there are other effectors between Ras and ERK, these proteins interact each other and constitute the thorough Ras/Raf/MEK/ERK signaling pathway. The pathway has profound effects on incidence of esophageal carcinoma and clinical applications of some chemotherapeutic drugs targeting the pathway. Further understanding of the relevant molecular mechanisms of Ras/Raf/MEK/ERK signaling pathway can be helpful for the development of efficient targeting therapeutic approaches which contribute to the treatment of esophageal cancer. In this article, roles of Ras/Raf/MEK/ERK signaling pathway in esophageal carcinoma as well as pharmacological targeting point in the pathway are reviewed.

Comparative observation of microcirculation and tissue healing process in gastrointestinal anastomosis with apposition or inverted suturing / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To compare microcirculation and tissue healing process in gastrointestinal anastomosis with apposition or inverted suture.</p><p><b>METHODS</b>The study was performed in adult rabbits. Animals were randomly assigned to two groups. In group A, small intestine was transected at 20 cm and 40 cm from duodenojejunal ligament and apposition sutures were performed at 20 cm and inverted sutures at 40 cm. In group B, transaction and anastomosis were at the same location with group A while the suturing method was reversed. Anastomotic microcirculation and number of capillary were observed in vivo with naked eyes to evaluate inflammatory response, collagen proliferation and healing of epithelium and smooth muscle in both groups at postoperative day 3, 7, 14 and 28.</p><p><b>RESULTS</b>In group A, tissue layers at the anastomosis were approximated tight and neat with mild inflammation and primary wound healing. In group B, displacement and poor alignment of layers were seen with severe inflammation and secondary wound healing. Low frequency of microcirculation was detected in group A at day 3, and blood flow velocity significantly increased at day 7. Blood flow velocity was close to normal at day 14 and completely restored to the normal level at day 28. Microcirculation was lower in group A than that in group B at each time point. There were more capillaries, lower number of inflammatory cells, less collagen proliferation, and better healing of anastomotic epithelium and smooth muscle in group A than group B.</p><p><b>CONCLUSION</b>Apposition suturing is better than inverted suturing in restoring local anastomotic microcirculation and healing of intestinal tissues.</p>

Regulatory effect of clearing-heat secreting-bile regulating-qi flow and activating blood circulation principle on cholecystokinin receptor / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To explore the regulatory effect of clearing-Heat secreting-bile regulating-Qi flow and activating blood circulation (CSRA) principle on cholecystokinin receptor (CCK-R) and its mechanism.</p><p><b>METHODS</b>Cholecystokinin (CCK) in serum of portal venous blood, maximum binding capacity (Bmax) and affinity (Kd) of CCK-R levels in gallbladder of guinea pigs allocated in four groups (control, high cholesterol, natural recovery and treated groups) were determined using radioimmunoassay and radioligand receptor assay (RRA). At the same time, changes of fasting volume (FV) and postprandial volume (PV) of gallbladder, fasting and postprandial bile (FB and PB) in gallbladder, gallbladder contraction rate (GCR) and cholesterol concentration (CC) in bile were observed.</p><p><b>RESULTS</b>Compared with the control group, after two weeks of high cholesterol feeding, increase of FV, FB, PV, PB and CC (P < 0.05), and decrease of GCR (P < 0.01) and Bmax were found in cholesterol group, but with no significant change in Kd and CCK level. The above-mentioned criteria were restored to normal range in the treated group.</p><p><b>CONCLUSION</b>CSRA principle could promote the recovery of gallbladder contraction by regulating CCK-R expression in it, its mechanism is possibly correlated with reduction of cholesterol concentration in bile.</p>