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2005年03月08日
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2005年03月08日
【期刊论文】Molecular Evolution of the SARS Coronavirus During the Course of the SARS Epidemic in China
周向军， *Epidemiology group: Jian-Feng He， † Guo-Wen Peng， Jun Min， De-Wen Yu， Wen-Jia Liang， Shu-Yi Zhang， Rui-Heng Xu‡ Virology group: Huan-Ying Zheng， † Xin-Wei Wu， † Jun Xu， Zhan-Hui Wang， Ling Fang， Xin Zhang， Hui Li， Xin-Ge Yan， Jia-Hai Lu， Zhi-Hong Hu， Ji-Cheng Huang， Zhuo-Yue Wan， ‡ Jin-Lin Hou， ‡ Jin-Yan Lin‡ Molecular biology group: Huai-Dong Song， † Sheng-Yue Wang， † Xiang-Jun Zhou， † Guo-Wei Zhang， Bo-Wei Gu， Hua-Jun Zheng， Xiang-Lin Zhang， Mei He， Kui Zheng， Bo-Fei Wang， Gang Fu， Xiao-Ning Wang， Sai-Juan Chen， Zhu Chen， ‡ Data analysis group: Pei Hao， ， † Hua Tang， † Shuang-Xi Ren， † Yang Zhong， † Zong-Ming Guo， Qi Liu， You-Gang Miao， Xiang-Yin Kong， Wei-Zhong He， Yi-Xue Li， Chung-I Wu， ‡ Guo-Ping Zhao， ‡§ Chinese University of Hong Ko
12 MARCH 2004 VOL 303 SCIENCE www.sciencemag.org，-0001，（）：
-1年11月30日
Sixty-one SARS coronavirus genomic sequences derived from the early, middle, and late phases of the severe acute respiratory syndrome (SARS) epidemic were analyzed together with two viral sequences from palm civets. Genotypes characteristic of each phase were discovered, and the earliest genotypes were similar to the animal SARS-like coronaviruses. Major deletions were observed in the Orf8 region of the genome, both at the start and the end of the epidemic. The neutral mutation rate of the viral genome was constant but the amino acid substitution rate of the coding sequences slowed during the course of the epidemic. The spike protein showed the strongest initial responses to positive selection pressures, followed by subsequent purifying selection and eventual stabilization.
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2005年03月08日
周向军， Xiaoming Yao， Ji-Fan Hu， Mark Daniels， Hadas Shiran， Xiangjun Zhou， Huifan Yan， Hongqi Lu， Zhilan Zeng， Qingxue Wang， Tao Li， and Andrew R. Hoffman
The Journal of Clinical Investigation|January 2003|Volume 111|Number 2，-0001，（）：
-1年11月30日
IGF-II is a mitogenic peptide that has been implicated in hepatocellular oncogenesis. Since the silencing of gene expression is frequently associated with cytosine methylation at cytosine-guanine (CpG) dinucleotides, we designed a methylated oligonucleotide (MON1) complementary to a region encompassing IGF2 promoter P4 in an attempt to induce DNA methylation at that locus and diminish IGF2 mRNA levels. MON1 specifically inhibited IGF2 mRNA accumulation in vitro, whereas an oligonucleotide (ON1) with the same sequence but with nonmethylated cytosines had no effect on IGF2mRNA abundance. MON1 treatment led to the specific induction of de novo DNA methylation in the region of IGF2 promoter hP4. Cells from a human hepatocellular carcinoma (HCC) cell line, Hep 3B, were implanted into the livers of nude mice, resulting in the growth of large tumors. Animals treated with MON1 had markedly prolonged survival as compared with those animals treated with saline or a truncated methylated oligonucleotide that did not alter IGF2 mRNA levels in vitro. This study demonstrates that a methylated sense oligonucleotide can be used to induce epigenetic changes in the IGF2 gene and that inhibition of IGF2 mRNA accumulation may lead to enhanced survival in a model of HCC.
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2005年03月08日
【期刊论文】A Novel Orthotopic Tumor Model to Study Growth Factors and Oncogenes in Hepatocarcinogenesis1
周向军， Xiaoming Yao， Ji-Fan Hu， Mark Daniels， Huifan Yien， Hongqi Lu， Hadas Sharan， Xiangjun Zhou， Zhilan Zeng， Tao Li， Youwen Yang， and Andrew R. Hoffman
Vol. 9, 2719-2726, July 2003，-0001，（）：
-1年11月30日
An orthotopic xenograft tumor model of hepatocellular carcinoma was created by injection of Hep 3B cells directly into the liver parenchyma of nude mice. Tumors were localized primarily in the njected lobe of the liver, beginning from the third week after tumor cell implantation. Thereafter, tumors grew rapidly, and animals usually died from hepatocellular carcinoma within 2 months. Insulin-like growth factor II, an embryonic growth factor and mitogen, s overexpressed in these tumors at both mRNA and protein levels. Oncogenes, such as c-myc, c-fos, and c-jun, are also up-regulated in this model.-Fetal protein can be detected shortly after implantation and correlates with tumor growth, and measurement of serum-fetal protein serves as an early biomarker to monitor the effect of antitumor therapy. Using this model, we have shown that inhibition of insulin-like growth factor II expression by a short methylated oligonucleotide prolongs survival. This in situ tumor model thus provides a fast, reliable, and reproducible means to study the therapeutic effect of inhibitors of growth factors and oncogenes in liver cancer.
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