Preparation and Properties of Thrombus-Targeted Urokinase/Multi-Walled Carbon Nanotubes (MWCNTs)-Chitosan (CS)-RGD Drug Delivery System.

In order to improve the therapeutic effect, prolong the action time and reduce the side effects of the first generation thrombolytic drug urokinase (UK), a novel UK/multi-walled carbon nanotubes (MWCNTs)-chitosan (CS)-arginine-glycine-aspartic acid (Arg-Gly-Asp) (RGD) drug delivery system was synthesized by chemical bonding/non covalent bond modification/ultrasonic dispersion. The results showed that the diameter of the UK/MWCNTs-CS-RGD drug delivery system was about 30-40 nm, there was a layer of UK was attached to the surface of the tube wall, and the distribution was relatively uniform. The average encapsulation efficiency was 83.10%, and the average drug loading was 12.81%. Interestingly, it also had a certain sustained-release effect, and its release law was best fitted by first-order kinetic equation. Moreover, the accelerated and long-term stability test results show that it had good stability. Compared with free UK, UK/MWCNTs-CS-RGD had thrombolytic effect in vitro. In addition, MTT experiment showed that the prepared MWCNTs-CS-RGD nanomaterials had good biocompatibility. A rabbit model of carotid artery thrombosis was used to conduct targeted thrombolysis experiments in vivo. Compared with free UK, UK/MWCNTs-CS-RGD could be enriched in the thrombosis site to achieve thrombus targeting. UK/MWCNTs-CS-RGD drug delivery system was expected to become an effective thrombolytic drug for targeted therapy of thrombosis.

Ginsenoside Rg3 sensitizes human non-small cell lung cancer cells to γ-radiation by targeting the nuclear factor-κB pathway.

At present, it is elusive how non-small cell lung cancer (NSCLC) develops resistance to γ-radiation; however, the transcription factor nuclear factor-κB (NF-κB) and NF-κB-regulated gene products have been proposed as mediators. Ginsenoside Rg3 is a steroidal saponin, which was isolated from Panax ginseng. Ginsenoside Rg3 possesses high pharmacological activity and has previously been shown to suppress NF-κB activation in various types of tumor cell. Therefore, the present study aimed to determine whether Rg3 could suppress NF-κB activation in NSCLC cells and sensitize NSCLC to γ-radiation, using an NSCLC cell line and NSCLC xenograft. A clone formation assay and lung tumor xenograft experiment were used to assess the radiosensitizing effects of ginsenoside Rg3. NF-κB/inhibitor of NF-κB (IκB) modulation was ascertained using an electrophoretic mobility shift assay and western blot analysis. NF-κB-regulated gene products were monitored by western blot analysis. The present study demonstrated that ginsenoside Rg3 was able to sensitize A549 and H1299 lung carcinoma cells to γ-radiation and significantly enhance the efficacy of radiation therapy in C57BL/6 mice bearing a Lewis lung carcinoma cell xenograft tumor. Furthermore, ginsenoside Rg3 suppressed NF-κB activation, phosphorylation of IκB protein and expression of NF-κB-regulated gene products (cyclin D1, c-myc, B-cell lymphoma 2, cyclooxygenase-2, matrix metalloproteinase-9 and vascular endothelial growth factor), a number of which were induced by radiation therapy and mediate radioresistance. In conclusion, the results of the present study suggested that ginsenoside Rg3 may potentiate the antitumor effects of radiation therapy in NSCLC by suppressing NF-κB activity and NF-κB-regulated gene products, leading to the inhibition of tumor progression.

[Relationship between changes of serum concentrations of antiangiogenic factors and disease progression in patients of pancreatic carcinoma].

OBJECTIVE: To investigate the relationship between TSP-1, Angiostatin and Endostatin serum concentrations and progression of pancreatic adenocarcinoma. METHODS: Fifty-six patients with suspected pancreatic cancer were enrolled in the study and divided into resectable group (n = 32) and unresectable group (n = 24) according to evaluation and staging with dual phase helical CT. Histopathologic examinations included postoperative final pathology and preoperative fine needle biopsies. Peripheral blood concentrations of antiangiogenic factors Angiostatin, Endostatin and TSP-1 were detected by using ELISA methods, selecting samples of health people as a control. RESULTS: Serum concentrations of antiangiogenic factors in pancreatic cancer group were significantly higher than those in health group (P < 0.01). Serum concentrations of Endostatin, Angiostatin and TSP-1 were significantly increased in unresectable group, and highly expressed in patients whom tumor sizes were greater than 2 cm and tumor invaded peripancreatic great vessels (P < 0.05). After operation, serum concentrations of Endostatin, Angiostatin and TSP-1 significantly decreased (P < 0.05). There were no significant difference between I, II stage group and III, IV group. CONCLUSIONS: Detection of serum concentrations of antiangiogenic factors may be used to evaluate the resectability of pancreatic cancer and may play important roles in growth, invasion and metastasis of pancreatic cancer.

[The relationship between the changes of proangiogenic factors serum concentrations and progression of pancreatic carcinoma patients].

OBJECTIVE: To investigate the relationship between VEGF, bFGF and IGF-1 serum concentration and progression of pancreatic carcinoma. METHODS: Fifty-six patients with pancreatic carcinoma were divided into resectable group (n = 32) and unresectable group (n = 24). Another group was normal group (n = 20). The expression and significance of these proangiogenic factors were respectively analyzed in different groups. RESULTS: For pancreatic carcinoma group, concentrations of VEGF and bFGF were significantly higher than these of normal group (P < 0.01). Serum VEGF was significantly correlated with the resection of pancreatic carcinoma (P < 0.05) while bFGF and IGF were not. According to univariate analysis, serum VEGF was correlated with tumor grade, nodal disease, vascular invasion, distant metastases and tumor stage. Serum bFGF was associated with tumor size and grade. Serum IGF-1 was correlated with vascular invasion. CONCLUSIONS: Angiogenic factors play important roles in growth, invasion and metastasis. Detection of serum proangiogenic factors may have potential value in diagnosis and prognosis of pancreatic carcinoma.

Effects of scorpion venom bioactive polypolypeptides on platelet aggregation and thrombosis and plasma 6-keto-PG F1alpha and TXB2 in rabbits and rats.

Effects of scorpion venom active polypeptide (SVAP) from scorpion venom of Buthus Martensii Karsch of Chinese on platelet aggregation in ex vivo and vitro in rabbits, thrombosis in carotid artery of rats and plasma 6-keto-PG F1alpha and TXB2 in rats were studied by the turbidimetry, the duplicated thrombosis model by electrostimulation and RIA, respectively. The results showed that SVAP 0.125, 0.25, 0.5 mg/ml inhibited significantly the rabbit platelet aggregation triggered by 0.3 U/ml thrombin, 10 microM ADP in vitro (P<0.05 or 0.01) and SVAP at the dose of 0.32, 0.64 mg/kg iv prolonged distinctively the occlusion time of thrombosis that were induced by electrical stimulation. Increased% of 0.16, 0.32 and 0.64 mg/kg were 30.16, 71.74, 98.27%, respectively, which showed a good dose-effect relationship. SVAP 0.22 mg/ml (in vitro) or 0.2, 0.4 mg/kg (in ex vivo) could obviously increase the plasma concentration of 6-keto-PG F1alpha, but slightly effect rats plasma concentration of TXB2 in vitro and in ex vivo and significantly increase of value of PG I2/TXA2, which suggested that the mechanism of the antithrombotic action of SVAP is related to the resistance against platelet aggregation, increase of the concentration of PG I2 in plasma.