Clinical application of the molecular target therapy for natural occurring tumors in small animals.

基因转移诱导肿瘤细胞死亡的研究1.犬p53基因转移腺病毒载体的构建及其抗肿瘤作用将本实验室克隆的犬p53基因插入到粘粒载体中，构建重组腺病毒。重组腺病毒载体对犬骨肉瘤细胞株有明显的杀伤作用，并呈病毒剂量依赖性。2.抗肿瘤基因治疗的新分子靶点在犬体内克隆了胸腺和活化调节趋化因子（TARC）和活化诱导胞苷脱氨酶（AID）作为抗肿瘤基因治疗的新分子靶点。3.体内基因转移方法的研究作为体内基因转移的基础研究，构建了含CTLA-4-Fce融合蛋白的重组表达质粒，并对其与IgE的结合能力进行了鉴定。 ...更多信息 ng标记cDNA接种犬肌肉，测定其表达效率。本研究分离培养了猫树突状细胞（DC），为记忆T细胞过继免疫治疗的基础研究奠定了基础。结果表明，在PBMC中加入IL-4和GM-CSF可分离培养猫树突状细胞，并对其表型和功能进行了研究。作为治疗犬多药耐药的基础研究，本研究对犬淋巴瘤中PgP蛋白的表达进行了研究，并对犬淋巴瘤中p53基因突变进行了研究。结果表明，p53基因突变与犬淋巴瘤的耐药性有关，而与PgP蛋白表达无关。少

Induction of tumor cell death by gene transfer1.Construction of Canine p53-adenoviral vector for gene transfer and its anti-tumor effectCanine p53 cloned in our laboratory was inserted cosmid vector and recombinant adenovirus was constructed. The recombinant adenoviral vector had cytoadal effect against canine osteosarcoma cell line in a viral dose dependent manner. The recombinant canine p53 adenovirus only showed additive effect against tumor cells when used with chemothepeutic agents.2.New molecular target for anti-tumor gene therapyAs new molecular targets for anti-tumor gene therapy, thymus and activation-regulated chemokine (TARC) and activation-induced cytidine deaminase (AID) was cloned in dogs. Furthermore, the recombinant expression plasmid containing CTLA-4-Fce fusion protein was constructed and its binding ability to IgE was confirmed.3.Investigation of in vivo gene transfer methodsAs a basic investigation of in vivo gene transfer into dogs, gene expression plasmid containi … More ng marker cDNA was inoculated into muscle of dogs and its efficacy of expression was determined. The expressed marker protein was seen only at injection sites, indicating lesional gene transfer methods for tumor bearing dogs was recommended.Immune-gene therapy based on the destruction of immuno-toleranceFeline dendritic cells (DC) was isolated and cultured for the basic research of adoptive immune-therapy using memory T cells. As a results, feline dendritic cells can be isolated and cultured by adding IL-4 and GM-CSF to PBMC and its phenotype and function were investigated. CTL induced by DCs were also investigated.Development of therapy for multi-drug resistance in chemotherapy in dogs and catsAs a basic research for the treatment of multi-drug resistance, PgP protein in canine lymphoma has been investigated Furthermore, mutation of p53 gene and canine lymphoma was also examined. As a result, the mutation of p53 gene was correlated with the drug resistance of canine lymphoma, however, it is not associated with the expression of PgP protrein. Less