Oncolytic herpes viral therapy is effective in the treatment of hepatocellular carcinoma cell lines

The rising incidence of hepatocellular carcinoma (HCC) in western countries, along with the poor prognosis offered by present-day treatment modalities, makes novel therapies for this disease necessary. Oncolytic herpes simplex viruses (HSV) are replication-competent viruses that are highly effective in the treatment of a wide variety of experimental models of human malignancies. This study seeks to investigate the effectiveness of oncolytic herpes viruses in the treatment of primary HCC cell lines. Sixteen commercially available human HCC cell lines were studied. G207 is an attenuated, replication-competent, oncolytic HSV engineered to selectively replicate within cancer cells. Cell lines were tested for viral sensitivity to G207 and their ability to support viral replication using standard cytotoxicity and viral replication assays. Eleven of 16 cell lines were moderately to highly sensitive to G207 viral oncolysis. HCC cell lines additionally demonstrated the ability to support viral replication in vitro with as high as 800-fold amplification of the administered viral dose observed. G207 is cytotoxic to, and efficiently replicates within, HCC cell lines in vitro. From these data, we suggest that oncolytic HSV therapy may have a role in the treatment of HCC, and in vivo studies are warranted. Presented in part at the 2005 American Hepato-Pancreato-Biliary Association Congress, Hollywood, Florida, April 14–17, 2005. Supported by grants R01CA75461 and R01CA72632 from the National Institutes of Health, and by grant MBC-99366 from the American Cancer Society (Yuman Fong).     

自发性高血压大鼠颈动脉血管平滑肌中抑癌基因P53和原癌基因c-jun、c-fos、c-myc mRNA表达的研究

目的探讨自发性高血压大鼠颈动脉中抑癌基因P53和原癌基因c-jun、c-fos、c-myc mRNA的表达.方法用逆转录聚合酶链式反应检测两种基因的表达水平.正常雄性大鼠作为对照组.结果 SHR颈动脉中,抑癌基因P53和原癌基因c-jun、c-fos、c-myc均有高表达,较WKY差异有显著性(P<0.05).结论自发性高血压大鼠颈动脉组织中抑癌基因P53和原癌基因c-jun、c-fos、c-myc均有高表达,癌基因的活化可能与自发性高血压大鼠颈动脉血管重构有关.     

Human Tumor–infiltrating Lymphocytes Transfected with Tumor Necrosis Factor Gene Could Augment Cytotoxicity to Autologous Tumor Cells

Human tumor–infiltrating lymphocytes (TILs) derived from pleural or ascitic fluid were incubated with recombinant interleukin 2 and transfected with human tumor necrosis factor (TNF) a gene by the lipofection procedure. The resulting TILs secreted significant amounts of TNF in the culture supernatant and exhibited cytotoxicity against established cell lines, such as K562 and Daudi, and autologous tumor cells. The TNF gene–transfected TILs exhibited an augmented killing of autologous tumor cells.     

Rb1基因第16内含子内21个碱基缺失1例

目地研究双眼视网膜母细胞瘤患者Rb1基因杂合性突变的分子生物学特性。方法应用PCR—SSCP直接测序技术检测双眼视网膜母细胞瘤患者白细胞DNA中Rb1基因杂合性突变。结果50例证实有Rb1基因杂合性突变的病例中有1例发生于第16内含子中可以用3种定位方法解释、具有相同序列的21个碱基缺失。结论这种极为少见的Rb1基因突变方式可能是由于破坏了正常拼接位点的结构而激活了“隐蔽拼接位点”，导致异常的Rb1基因mRNA产生或由此影响整个拼接过程。     

Cationic Lipid-Based Gene Delivery Systems: Pharmaceutical Perspectives

Gene delivery systems are designed to control the location of administered therapeutic genes within a patient's body. Successful in vivo gene transfer may require (i) the condensation of plasmid and its protection from nuclease degradation, (ii) cellular interaction and internalization of condensed plasmid, (iii) escape of plasmid from endosomes (if endocytosis is involved), and (iv) plasmid entry into cell nuclei. Expression plasmids encoding a therapeutic protein can be, for instance, complexed with cationic liposomes or micelles in order to achieve effective in vivo gene transfer. A thorough knowledge of pharmaceutics and drug delivery, bio-engineering, as well as cell and molecular biology is required to design optimal systems for gene therapy. This mini-review provides a critical discussion on cationic lipid-based gene delivery systems and their possible uses as pharmaceuticals.     

转人GM—CSF基因人膀胱癌细胞株的建立及体外生物学特性

经逆转录病毒载体将人GM-CSF基因导入人膀胱癌细胞株BIU-87细胞中,建立了转基因细胞株BIU/GM。经流式细胞仪行细胞DNA周期分析表明GM-CSF基因的导人及表达对BIU-87细胞的增长无影响。免疫荧光测定发现转GM-CSF基因及表达不能促进BIU-87细胞表面HLA-ABC、DR、DQ抗原的表达。转基因瘤细胞株经6000rad X射线照射灭活后,丧失增殖能力,逐步死亡,但能维持一定水平的GM-CSF分泌活性达两周以上。从而为制备灭活的转基因瘤苗提供了初步经验。     

Absent chondrodysplasia punctata in a male with an Xp terminal deletion involving the putative region for CDPX1 locus

This is a follow-up report on a male patient with a 46, Y, r(X) karyotype. Although he had no clinico-radiological features of X-linked recessive chondrodysplasia punctata (CDPX1), molecular studies revealed an Xp terminal deletion involving the putative region for the CDPX1 locus (PABX-DXS31). We suspect that the absence of CDPX1 may be attributable to the nature of the disease and the extreme short stature of the patient (mean – 5.6 S.D.). © 1993 Wiley-Liss, Inc.     

人卵巢癌中肿瘤转移抑制基因nm23-H1编码蛋白的表达

目的：探讨人卵巢癌标本中，肿瘤转移抑制基因ｎｍ２３－Ｈ１编码蛋白ＮＤＰＫ－Ａ表达的临床意义及其与预后的关系。方法：应用免疫组织化学抗生蛋白链菌素－过氧化酶结合（Ｓ－Ｐ）法，检测５８例人卵巢癌标本中ｎｍ２３－Ｈ１蛋白水平。结果：ｎｍ２３－Ｈ１蛋白的表达与患者手术时是否有淋巴结及大网膜转移相关（Ｐ〈０．０５），但原发灶与转移灶间的阳性表达率相差不显著；与患者术后生存时间密切相关（Ｐ〈０．０１），术后生     

Selection of Single Nucleotide Polymorphisms for Association Studies in Candidate Genes

Comparison of polymorphic sites such as single nucleotide polymorphisms (SNPs) within a gene between cases and controls may be useful for establishing a role of this gene in disease susceptibility. The approach includes two steps: the first step is the discovery of the different SNPs within the candidate gene and the second step is the association testing per se that can be done on the entire set of sites discovered or on a subset of these sites only. Selecting a subset of sites may increase the power to detect the association with the candidate gene since a smaller number of tests would then be performed. We proposed a strategy to select sites within a candidate gene and applied it on the Genetic Analysis Workshop 12 candidate gene data. Using these selected sites, we detected an association with candidate genes 1 and 6. © 2001 Wiley‐Liss, Inc.