Inhibition of Metastatic Hepatocarcinoma by Combined Chemotherapy with Silencing VEGF/VEGFR2 Genes through a GalNAc-Modified Integrated Therapeutic System

Hepatocellular carcinoma (HCC) is a highly malignant tumor related to high mortality and is still lacking a satisfactory cure. Tumor metastasis is currently a major challenge of cancer treatment, which is highly related to angiogenesis. The vascular endothelial growth factor (VEGF)/VEGFR signaling pathway is thus becoming an attractive therapeutic target. Moreover, chemotherapy combined with gene therapy shows great synergistic potential in cancer treatment with the promise of nanomaterials. In this work, a formulation containing 5-FU and siRNA against the VEGF/VEGFR signaling pathway into N-acetyl-galactosamine (GalNAc)-modified nanocarriers is established. The targeting ability, biocompatibility and pH-responsive degradation capacity ensure the efficient transport of therapeutics by the formulation of 5-FU/siRNA@GalNAc-pDMA to HCC cells. The nano-construct integrated with gene/chemotherapy exhibits significant anti-metastatic HCC activity against C5WN1 liver cancer cells with tumorigenicity and pulmonary metastasis in the C5WN1-induced tumor-bearing mouse model with a tumor inhibition rate of 96%, which is promising for future metastatic HCC treatment.     

Raman spectroscopic analysis of apoptosis of single human gastric cancer cells

A drug (5-FU) was employed to treat the gastric carcinoma cells and induce apoptosis of the cancer cells. Raman spectra obtained from single gastric carcinoma cells and the induced apoptotic cells through scan-excitation mode were used to analyze the effectiveness of the treatment. The major difference of the apoptotic cells from the cancer cells are the reduction in intensities of vibration bands generated by cellular lipids, proteins and nucleic acids. In particular, large intensity reduction in nucleic vibrations at 782, 1092, 1320, 1340, and 1578 cm⁻¹ was observed upon apoptosis of the gastric carcinoma cells. Up to 45% reduction in the magnitude of the 782 cm⁻¹ peak in Raman spectra of the apoptotic cells was observed, which suggests the breakdown of phosphodiester bonds and DNA bases. We showed that the principal components analysis (PCA), a multivariate statistical tool, can be used to distinguish single apoptotic cells and gastric carcinoma cells based on their Raman spectra.     

光动力作用促人肝癌细胞HepG2凋亡及对bax，bcl-2蛋白表达的影响

应用流式细胞仪分析光动力作用后细胞凋亡及免疫组化染色检测凋亡相关蛋白bcl-2蛋白，bax蛋白表达水平．发现血卟啉光动力实验组人肝癌细胞HepG2凋亡率达24．23±1．86％，与对照组相比，差异非常显著（P〈0．01）；光动力作用后凋亡相关蛋白bcl-2表达显著高于对照组（P〈0．05）；实验结果显示血卟啉光动力作用具有诱导人肝癌细胞HepG2凋亡的生物学效应，而凋亡调控蛋白bcl-2表达水平的降低可能是血叶林光动力作用诱导人肝癌细胞HepG2凋亡的一个重要机制．     

糖类研究LIV.肝癌相关糖抗原SM_3寡糖链的合成研究

SM_3是寡糖链中带有硫酸酯基的酸性鞘糖脂,在正常人肝中含量极少,而在培 养的人肝细胞癌细胞系和人肝癌细胞手术标本中均有明显堆积。因此,SM_3可望作 为人肝细胞癌的肿瘤相关糖抗原,建立机体的特异性主动免疫。本文经过11步反应 ,首次合成了带连接臂的SM_3寡糖链,为今后合成具有更高分子量的糖基缀合物并 研究其抗肿瘤免疫原性奠定了基础。     

Raman spectroscopic analysis of breast cancer tissues: identifying differences between normal,invasive ductal carcinoma and ductal carcinoma in situ of the breast tissue

A relatively non‐destructive method employing Raman spectroscopy for the analysis of histopathological specimens is described. Raman spectroscopy has allowed qualitative analysis of the same specimen used for histopathological evaluation. Breast cancer tissues have been analysed to demonstrate the feasibility of the chemical changes taking place in the biological tissue, which can be identified precisely, and the results are reproducible. Raman analysis of tissue sections provides distinct spectra that can be used to distinguish between the nuclear grades of ductal carcinoma in situ (DCIS) and invasive ductal carcinoma (IDC) of the breast. Sixty cases of breast carcinoma including DCIS and IDC and seven cases of normal breast tissues were studied employing the Raman spectroscopic technique. This study reports for the first time spectral differences between DCIS grades. It is concluded that Raman spectroscopy can objectively distinguish between DCIS and IDC grades and is non‐destructive and reproducible. It should become possible in future to use Raman spectroscopy as an informative and quantitative method suitable for classification of grades and diagnosis of breast carcinoma. Copyright © 2007 John Wiley & Sons, Ltd.     

柴胡逆转肝细胞癌多药耐药作用与相关机制的研究

选用对VCR天然耐药肝癌细胞株Bel-7402为对象来研究柴胡逆转MDR效果与相关的机制,以寻找一种新型的具有多药耐药逆转活性的中药.结果表明,柴胡具有逆转肝细胞癌多药耐药作用,并与抗癌药物VCR有协同作用.柴胡对人肝癌Bel-7402细胞株具有多药耐药逆转作用,提高了耐药细胞内的VCR含量,增加了VCR对细胞G2期阻滞作用,抑制了P-170糖蛋白的表达,抑制MDR1/mRNA的表达,提高了TopoαmRNA水平.     

ANXA2 enhances the progression of hepatocellular carcinoma via remodeling the cell motility associated structures

Hepatocellular carcinoma (HCC) ranks as the fifth most common malignancy worldwide. The detailed mechanism of signal regulation for HCC progression is still not known, and the high motility of cancer cells is known as a core property for cancer progression maintenance. Annexin A2 (ANXA2), a calcium-dependent phospholipids binding protein is highly expressed in HCC. To study the roles the excessively expressed ANXA2 during the progression of HCC, we inhibited the ANXA2 expression in SMMC-7721 cells using RNAi, followed by the analysis of cell growth, apoptosis and cell motility. To explore the relationship between the cell behaviors and its structures, the microstructure changes were observed under fluorescence microscopy, laser scanning confocal microscopy and electron microscopy. Our findings demonstrated that down-regulation of ANXA2 results in decreased the cell proliferation and motility, enhanced apoptosis, suppressed cell pseudopodia/filopodia, inhibited expression of F-actin and β-tubulin, and inhibited or depolymerized Lamin B. The cell contact inhibition was also analyzed in the paper. Take together, our results indicate that ANXA2 plays an important role to enhance the malignant behaviors of HCC cells, and the enhancement is closely based on its remodeling to cell structures.     

Isolation of a new triterpene derivative and in vitro and in vivo anticancer activity of ethanolic extract from root bark of Zizyphus nummularia Aubrev

The various parts of Zizyphus nummularia has been used traditionally in several disease conditions. However, its anticancer activity and mechanism of action remain to be elucidated. Considering this, the objective of this study was to isolate, identify and screen for possible anticancer activity in vitro and in vivo of the ethanolic extract (EE) and isolated identified compound (IC) from Z. nummularia root bark. The in vitro activity against human breast cancer, leukaemia, ovarian cancer, colon adenocarcinoma and human kidney carcinoma cell lines was determined. The in vivo activity in female Swiss albino mice against Ehrlich ascites carcinoma (EAC) was determined. The isolated compound is a new triterpene derivative. EE/IC showed cytotoxicity against different cell lines. The administration of EE/IC decreased tumour parameters such as tumour volume, viable tumour cell count and increased body weight, haematological parameters and life span in comparison to the EAC control mice.