Preparation of Juglone-loaded PLGA Nanoparticles and Its Anti-tumor Effect on Melanoma A375 Cells in Vitro / 中国实验方剂学杂志

Objective: To prepare Juglone-loaded poly lactic-co-glycolic acid nanoparticles (Jug-PLGA-NPs), and investigate their physicochemical properties, release characteristics in vitro and anti-tumor activities on A375 melanoma cells in vitro. Method: Jug-PLGA-NPs were prepared by emulsification-solvent evaporation method. Then the particle size, encapsulation efficiency, drug loading rate and in vitro release characteristics were investigated. Fluorescence microscopy was used to observe the uptake of PLGA-NPs in vitro. The distribution of PLGA-NPs in BALB/c nude mice after tail vein injection was observed by the small living animal imaging system. Their inhibition effect on proliferation of A375 cells was detected by thiazolyl blue tetrazolium bromide (MTT) assay. Apoptosis rate and cell cycle detection were performed by flow cytometry. Western blot was used to determine the protein kinase B (Akt), phosphorylated Akt (p-Akt) and cyclinD1. Result: The average particle size of the prepared Jug-PLGA-NPs was (149.6±21.5) nm, entrapment rate of (68.39±2.51)%, and drug-loading rate of (5.07±0.98)%, showing good sustained-release characteristics. PLGA-NPs showed good penetration and targeting properties in cellular uptake in vitro and in vivo imaging. Different concentrations of Jug-PLGA-NPs could significantly inhibit the proliferation and promote apoptosis of A375 cells in a time and concentration dependent manner (P1 expression (P0/G1 phase (PConclusion: The Jug-PLGA-NPs are easy to prepare and have good sustained-release characteristics, tumor targeting and anti-tumor ability, providing a new pharmaceutical dosage form for the future clinical application of Jug.

Relationship between BRCA1 mRNA expression in tumor cells from malignant effusions and chemosensitivity to cisplatin in patients with metastatic malignant effusions / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To explore the mRNA expression of breast cancer susceptibility gene 1 (BRCA1) in tumor cells isolated from malignant pleural and peritoneal effusions, and the predictive role of BRCA1 related to the efficacy of cisplatin-based chemotherapy.</p><p><b>METHODS</b>Tumor cells were isolated from malignant pleural and peritoneal effusions of 31 cancer patients. The response of these tumor cells to cisplatin was determined by CCK8 assay. Real time quantitative RT-PCR was used to examine the BRCA1 mRNA level in the primary culture cancer cells.</p><p><b>RESULTS</b>The expression level of BRCA1 mRNA was 0.618 (0.014 - 18.063) in primary culture tumor cells. The IC(50) of DDP was 2.809 µg/ml in the primary culture tumor cells (0.118 - 19.439 µg/ml). Both BRCA1 mRNA expression and the tumor cells IC(50) of DDP were not significantly related with patient age, gender, the type of primary tumor, whether to accept the chemotherapy and effusion type (P > 0.05). The level of BRCA1 mRNA was negatively correlated with the chemosensitivity in terms of IC(50) of cisplatin (P < 0.001).</p><p><b>CONCLUSION</b>Assessment of expression level of BRCA1 mRNA may be useful in predicting the efficacy of cisplatin-based chemotherapy in patients with metastatic malignant effusions.</p>

Prognostic significance of ERCC1 mRNA expression in patients with non-small cell lung cancer receiving platinum-based chemotherapy / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To investigate the correlation of the mRNA expression level of excision repair cross-complementing group 1 (ERCC1) gene with clinicopathological parameters and clinical outcome in patients with non-small cell lung cancer (NSCLC) receiving platinum-based chemotherapy.</p><p><b>METHODS</b>The mRNA expression of ERCC1 in formalin-fixed paraffin-embedded primary tumor specimens was measured by real-time quantitative reverse transcriptase polymerase chain reaction. The association between ERCC1 expression levels and clinicopathological parameters in NSCLC patients was analyzed.</p><p><b>RESULTS</b>The median value of ERCC1 mRNA expression level compared with beta-actin in tumor specimens of 61 NSCLC patients was 0.48. There was no correlation between ERCC1 expression and clinicopathological parameters. Patients with low expression of ERCC1 mRNA (less than 0.35, 0.28, respectively) had a significantly longer median time to progression (TTP) (14.3 vs. 8.0 months, P = 0.028) and overall survival (OS) (28.4 vs. 12.9 months, P = 0.0064) than those with high expression. Multivariate analysis showed that a low ERCC1 mRNA expression was an independent factor for OS.</p><p><b>CONCLUSION</b>Our findings suggest that intratumoral ERCC1 mRNA expression level, although is uncorrelated with clinicopathological parameters, is an independent predictive marker for survival of the patients with NSCLC receiving platinum-based chemotherapy, and may provide critical information for personalized chemotherapy.</p>

Inhibitory effect of oxaliplatin in combination with hyperthermia on angiogenesis / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To study the effect of oxaliplatin in combination with hyperthermia on angiogenesis in vitro and in vivo.</p><p><b>METHODS</b>MTT method was used to observe the influence of oxaliplatin on the proliferation of human umbilical vein endothelial cells (HUVEC) or human colon cancer cells (LOVO). The influence of oxaliplatin on HUVEC migration was evaluated by Transwell. Chick embryo chorioallantoic membrane (CAM) model was used to check whether the neovascularization of CAM could be suppressed in vivo.</p><p><b>RESULTS</b>The survival rate of HUVEC was 80.1% - 42.5% within a range of 0.5 - 16 microg/ml and was negatively correlated with the concentration (correlation coefficient was - 0. 943, P = 0.005). The survival rate of LOVO cells within those doses was more than that of HUVEC. There was a synergistic antiangiogenic effect when a combination of oxaliplatin (0.5 microg/ml, 1 microg/ml and 16 microg/ml) with hyperthermia was used while additional effect was shown by the combinatioin of oxaliplatin (2 microg/ml, 4 microg/ml and 8 microg/ml) and hyperthermia in vitro. Oxaliplatin inhibited migration of HUVEC in vitro at low doses (0.25 - 2 microg/ml), and also suppressed angiogenesis of CAM in vivo at doses of 1 -4 microg/ml.</p><p><b>CONCLUSION</b>The results of this experiment showed that low dose of oxaliplatin has anti-angiogenic effect in vitro, while in combination with hyperthermia has additional effect both in vivo and in vitro.</p>

Effect of arsenic trioxide on drug transporting molecules in acute promyelocytic leukemia cell line / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To study the effect of arsenic trioxide (As2O3) on expression of drug transporting molecules in APL MR2 cell line.</p><p><b>METHODS</b>MR2 resistant to all-trans retinoic acid (ATRA) and non-ATRA resistant APL cell line NB4 was used in this in vitro study. Expression of P-glycoprotein (Pgp), multidrug resistance protein (MRP) and lung resistance-related protein (LRP) was detected by immunocytochemical assay.</p><p><b>RESULTS</b>The expression of Pgp was significantly higher in MR2 (30%-40%) than in NB4 (10%-20%) (P < 0.001), and that of MRP was also higher in MR2 (56.9 +/- 3.4-21.2 +/- 1.1) than in NB4 (20.6 +/- 5.3-16.7 +/- 1.2) (P < 0.001). As2O3 at concentrations ranging from 0.5 approximately 2.0 micromol/L could significantly decrease the expression of Pgp and MRP, but not that of LRP. The decrease in the expression of Pgp and MRP in MR2 cell line was negatively correlated with the dose and duration of action of As2O3.</p><p><b>CONCLUSION</b>Pgp and MRP, but not LRP, may be the sensitive targets of As2O3 to overcome drug-resistance. ATRA might be the substrates of Pgp and MRP.</p>