BACKGROUND: With the development of nanotechnology, a new system for the delivery of drugs by magnetic nanovectors has been proposed. Within a magnetic field, the system can implement site-specific drug administration, thereby raising drug concentration at the lesion focus, elevate therapeutic effects, and reduce side effects.OBJECTIVE: To study the preparation of magnetic poly D, L-lactide-co-glycolic acid phenylarsine oxide nanoparticles (M-PLGA-PAO-NPs) and to evaluate characteristics of the prepared nanoparticles.DESIGN: Several factors influencing nanoparticle characteristics were selected for single-factor tests. Then, according to experimental results, and in conjunction with orthogonally designed statistics, the optimized prescription was obtained. SETTING: Department of Special Diagnosis, Changhai Hospital, Second Military Medical University of Chinese PLA.MATERIALS: The study was performed at the Department of Pharmaceutics, School of Pharmacy, Second Military Medical University of Chinese PLA from January 2005 to March 2006. The reagents used were as follows: phenylarsine oxide (Sigma, USA), poly D, L-lactic-co-glycolic acid (Shandong Medical Apparatus Institute, China), ferroso-ferric oxide (nanometer, Sigma, USA), polyvinyl alcohol (PVA1788, Beijing Organic Chemical Industry Plant, China). Methylene dichloride and other agents were all analytical grade and purchased from Shanghai Sinopharm Chemical Reagent Co., Ltd, China.METHODS: M-PLGA-PAO-NPs were prepared through an emulsion-evaporation process. Nanoparticle shape was observed by transmission electron microscopy. Magnetism was determined by a vibrating sample magnetometer. The size and diametral distribution of nanoparticles were determined by a laser particle size analyzer. The encapsulation ratio and drug loading of phenylarsine were measured by high performance liquid chromatography (HPLC). The percentage of phenylarsine oxide release in vitro was calculated [the percentage of phenylarsine oxide release in vitro =(total dose of phenylarsine oxide-residual dose of phenylarsine oxide)/ total dose of phenylarsine oxide].MAIN OUTCOME MEASURES: The shape, size, drug loading, encapsulation ratio and release in vitro of M-PLGA-PAO-NPs.RESULTS: The prepared nanoparticles had an average encapsulation ratio of 34.2%. Drug loading of 5 batches of nanoparticles was 3.06%, 3.15%, 3.18%, 3.21%, and 3.41%, respectively, with an average drug loading of 3.20%. Drug loading difference was small between batches, indicating good stability and reproducibility of the technology. M-PLGA-PAO-NPs were spherical, smooth, evenly distributed and non-adhesive. Ferrosoferric oxide microparticles, which exhibited unevenly dispersed black opacities, were found in the magnetic microparticles. Nanoparticles were in a narrow size range, with an average diameter of 290 nm (range 140-500 nm). When the magnitude and the direction of the outside magnetic field were changed, nanoparticles showed different intensities of magnetization. This indicated that M-PLGA-PAO-NPs had a certain magnetic response. The in vitro nanoparticle-release curve indicated that drug release was initially fast followed by a slow controlled release, and on day 8, it was basically stable.CONCLUSION:The experiment acquires a satisfactory technique for preparation of M-PLGA-PAO-NPs. The prepared M-PLGA-PAO-NPs were well targeted and exhibited slowly controlled drug release effects.

Objective: To study the effect of intracellular-free calcium and the expression of Fas and Fas L on the process of pancreatic carcinoma cell apoptosis. Methods: Apoptosis induced by 2 μmol/L arsenic trioxide in pancreatic cancer cell lines SW-1990 was investigated.Concentration of intracellular-free calcium （［Ca2+］i） was determined by Fura-2a fluorescein load technique. Fas and FasL were determined by flow cytometry. Results: Pancreatic cancer cells treated with 2 μmol/L arsenic trioxide presented apoptotic features: intact cell membrane, chromatin condensation, nucleic fragmentation and apoptotic body formation; agarose electrophoresis showed marked ladder; flow cytometery analysis showed a sub-G1 cell peak. In the process of pancreatic carcinoma cell apoptosis Fas and FasL and the ［Ca2+］i were significantly higher than that in the control. Conclusion: The pancreatic cancer cell apoptosis induced by arsenic trioxide is related to Fas and FasL expression by the cancer cells and the ［Ca2+］i increase in the cancer cells.

Objective: To select the telomerase positive cancer cell lines of gastrointestinal tract and to provide a convinced methodology for future telomerase study. Methods: Fifteen cancer cell lines (carcinoma of stomach 4, of liver 6, of pancreas 2, of colon 3) were cultured and telomerase activity were detected by TRAP-ELISA. The normal hepatic cells were taken as control. Results: Thirteen cell lines were telomerase positive in the 15 lines(86.7%). Conclusion: Most of gastrointestinal tract cancer lines express telomerase, indicating the detection of telomerase activity has clinical potential.

Objective:To study the preparation technique for magnetic poly D,L-lactide-co-glycolide phenylarsine oxide nanoparticles (M-PLGA-PAO-NPs) and to characterize the resultant product. Methods: M-PLGA-PAO-NPs were prepared by using emulsion-evaporation process. The morphology of the prepared nanoparticles were observed by transmission electron microscope and the magnetism of the particles was determined by vibrating sample magnetometer. Meanwhile, we also evaluated the mean diameter, encapsulation ratio, and drug loading rate of the particles. Results: The nanoparticles had a regular spherical surface, with 80% of them having a diameter of 140-500 nm. We also found that the drug loading rate of the particles was 3.2% and the mean encapsulation ratio was 34.2%. The drug had satisfactory magnetic property. Conclusion: Our method can obtain M-PLGA-PAO-NP with satisfactory quality, it is simple-to-use and the prepared particles can meet the requirement of pharmaceutics.

Objective: To study the effect of intracellular free calcium and the expression of Fas and Fas L on the process of pancreatic carcinoma cell apoptosis. Methods: Apoptosis induced by 2 ?mol/L arsenic trioxide in pancreatic cancer cell lines SW 1990 was investigated.Concentration of intracellular free calcium ([Ca 2+ ]i) was determined by Fura 2a fluorescein load technique. Fas and FasL were determined by flow cytometry. Results: Pancreatic cancer cells treated with 2 ?mol/L arsenic trioxide presented apoptotic features: intact cell membrane, chromatin condensation, nucleic fragmentation and apoptotic body formation; agarose electrophoresis showed marked ladder; flow cytometery analysis showed a sub G 1 cell peak. In the process of pancreatic carcinoma cell apoptosis Fas and FasL and the [Ca 2+ ]i were significantly higher than that in the control. Conclusion: The pancreatic cancer cell apoptosis induced by arsenic trioxide is related to Fas and FasL expression by the cancer cells and the [Ca 2+ ]i increase in the cancer cells.

Objective:To detect the activity of telomerase in pleural effusion, providing data for clinical diagnosis. Methods: The cells of tuberculous and cancerous pleural effusion were collected from 104 patients. TRAP PCR ELISA methods were used to detect the activity of telomerase. Results: The relative activity of telomerase in 54 cases of malignant pleural effusion (0.396?0.018) was obviously higher than that in the tuberculosis pleural effusion (0.003?0.021) ( P