Combinatory use of replication-competent adenoviruses and chemotherapeutic agents produces anti-tumor effects on human esophageal carcinoma cells

具有复制能力的腺病毒与化疗药物联合使用对人食管癌细胞产生抗肿瘤作用

• 批准号: 23591951
• 负责人: TAGAWA Masatoshi
• 金额: $ 3.24万
• 依托单位: Chiba Cancer Center (Research Institute)
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011 至 2013
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23591951/
• 关键词: 遺伝子; ウイルス; 癌; 受容体; 化学療法; CD46; 抗腫瘍効果; 食道がん; アデノウイルス; 細胞死; p５３; 食道癌; CD46分子; 細胞周期

We examined a novel therapeutic strategy for intractable cancer in particular esophageal carcinoma. We replaced a transcriptional regulatory region of the E1 region-encoded genes in adenoviruses (Ad) with a 5' region of a gene that was highly expressed in human tumors but not in normal tissues such as midkine, survivin and cyclooxygenase-2. We also changed the fiber region of conventional type 5 Ad, which played a key role in infecting target cells, with a type 35-derived fiber region. The modification increased the viral infectivity since an expression level of the CAR molecules, which were a cellular receptor of type 5 Ad, were often down-regulated in human tumors. In contract, the expression of CD46 molecules, which are the major receptor of type 35 Ad, is rather up-regulated in human tumors. The fiber replacement greatly enhanced Ad infectivity in CAR-low tumors and subsequently enhanced the Ad-mediated cytotoxicity, and produced combinatory effects with anti-cancer agents.

我们研究了一种针对顽固性癌症，特别是食管癌的新治疗策略。我们将腺病毒 (Ad) 中 E1 区编码基因的转录调控区替换为在人类肿瘤中高表达但在正常组织中不表达的基因的 5' 区，例如中期因子、生存素和环氧合酶-2。我们还用 35 型衍生的纤维区域改变了在感染靶细胞中发挥关键作用的传统 5 型 Ad 的纤维区域。这种修饰增加了病毒的感染性，因为 CAR 分子（5 型 Ad 的细胞受体）的表达水平在人类肿瘤中经常下调。相反，CD46 分子（35 Ad 型的主要受体）的表达在人类肿瘤中相当上调。纤维替代物大大增强了 CAR-low 肿瘤中的 Ad 感染性，随后增强了 Ad 介导的细胞毒性，并与抗癌药物产生了联合作用。

项目成果

Upregulated p53 expression activates apoptotic pathways in wild-type p53-bearing mesothelioma and enhances cytotoxicity of cisplatin and pemetrexed

• DOI: 10.1038/cgt.2011.86
• 发表时间: 2012-03-01
• 期刊: CANCER GENE THERAPY
• 影响因子: 6.4
• 作者: Li, Q.;Kawamura, K.;Tagawa, M.
• 通讯作者: Tagawa, M.

A Cancer-targeting Ligand Strongly Enhances Oncolytic Activity of a Conditionally Replicative Adenovirus

癌症靶向配体强烈增强条件复制腺病毒的溶瘤活性

• 发表时间: 2013
• 作者: Yuki Yamamoto;Kazuki Miura;Naoko Goto;Kenta Narumi;Shumpei Ohnami;Teruhiko Yoshida;Masatoshi Tagawa;Kazunori Aoki
• 通讯作者: Kazunori Aoki

Antitumor effect of chondroitin sulfate-coated ternary granulocyte macro phage-colony-stimulating factor plasmid complex for ovarian cancer

硫酸软骨素包被的三元粒细胞巨噬细胞集落刺激因子质粒复合物对卵巢癌的抗肿瘤作用

• DOI: 10.1002/jgm.1647
• 发表时间: 2012
• 期刊: JOURNAL OF GENE MEDICINE
• 影响因子: 3.5
• 作者: Katsuyuki Hamada;他
• 通讯作者: 他

Expression of a murine homolog of apoptosis-inducing human IL-24/MDA-7 in murine tumors fails to induce apoptosis or produce anti-tumor effects

诱导细胞凋亡的人 IL-24/MDA-7 的鼠同源物在小鼠肿瘤中的表达未能诱导细胞凋亡或产生抗肿瘤作用

• 发表时间: 2012
• 期刊: Cellular Immunology
• 影响因子: 4.3
• 作者: Nagakawa;Hiroyasu;Shimozato;Osamu;Yu;Ling;Wada;Akihiko;Kawamura;Kiyoko;Li;Quanhai;Chada;Sunil;Tada;Yuji;Takiguchi;Yuichi;Tatsumi;Koichiro and Tagawa;Masatoshi
• 通讯作者: Masatoshi