2000 Fiscal Year Annual Research Report

子宮体癌における腫瘍ワクチン開発の基礎的研究(副題:c-erbB2をコードするfusion geneを含んだplasmid DNAを用いた腫瘍ワクチンの開発)

Research Project

Project/Area Number	10470349
Research Institution	Nihon University
Principal Investigator	佐藤和雄日本大学, 医学部, 教授 (80010180)
Co-Investigator(Kenkyū-buntansha)	大谷香日本大学, 医学部, 助手 (40246872) 高見毅司日本大学, 医学部, 助手 (90297812) 坂元秀樹日本大学, 医学部, 助教授 (80158922)
Keywords	DNA ワクチン / c-erbB2
Research Abstract	平成10、11年度実績報告に記載したように、当初予定した領域のc-erb-B2 plasmid DNAがimmunoantigenとして充分ではなかったため、平成12年度は他のgenomic DNAの領域について検討を行った。現在までに数個のconstructを得たが、いずれもそのimmunoantigen活性は弱く、十分なimmunoantigenとなり得る領域の同定には至らず、vaccinationの基礎実験に用いるc-erb-B2 plasmid DNAの作成は結果として完了できなかった。一方我々は本科研費の援助を受け、アクチンフィラメントー細胞膜結合に関与する蛋白ezrinが子宮体癌の浸潤・転移に関与することを国内外で初めて見い出し報告した(K.Ohtani, et al.,Cancer let.144:1-8,1999)。Ezrin antisenseは低転移性および高転移性子宮体癌の浸潤のみを特異的に抑制し、細胞増殖には影響を与えなかった。またezrinは、マウスのmethylcholanthren誘発肉腫のtumor-associated transplantation antigenであることも同定されており、以上よりezrinが子宮体癌の浸潤や転移に関与するtumor antigenとして作用する可能性が示唆された。そのため平成12年度は、前述のごとくc-erb-B2のplasmid DNAの作成が困難であったことより、c-erbB2と同様の方法を用いてimmunoantigenとなり得るezrin plasmid DNAの作成を試みた。現在までにezrin全領域およびアクチン結合領域であるC末端領域をcodeするplasmid DNAを得ることができた。さらに、fusion proteinの発現やimmunoantigen活性については現在検討中である。

Research Products
(10 results)

All Other

All Publications (10 results)

[Publications] H.Sakamoto, et al: "Thymidine phosphorylase expression is predominantly observed in stroma of well-differentiated adenocarcinoma of endometrium and correlates with a frequentcy of vascular involvement"Gynecologic Oncology. 72. 298-305 (1999)
[Publications] H.Sakamoto, et al.: "Gene expression in primary, metastatic and recurrent lesions of endometrial cancer."Gynecol gic and Obstet ric Investigation. 192. 1-11 (1999)
[Publications] K.Ohtani, et al.: "Ezrin, a membrane-cytoskeletal linking protein, is involved in the process of invasion of endometrial cancer cells."Cancer letters. 144. 1-8 (1999)
[Publications] K.Kinoshita, et al.: "Steroid hormone receptors and multi-drug resistant genes expression in gynecologic cancers."Nihon University Journal of Medicine. 41. 1-14 (1999)
[Publications] K.Ohtani, et al.: "Molecular pathogenesis of endometrial hyperplasia and adenocarcinoma."Nihon University Journal of Medicine. 41. 181-193 (1999)
[Publications] Y.Nakayama, et al.: "Tamoxifen and gonadal steroids inhibit colon cancer growth, thymidylate synthase, survivin and telomerase expression through estrogen receptor beta mediated system."Nihon University Journal of Medicine. 42. 137-150 (2000)
[Publications] Y.Nakayama, et al.: "Tamoxifen and gonadae steroids inhibit colon cancer growth is association with inhibition of thymidylate synthase, survivin and telomerase expression through estrogen receptor beta mediated system."Cancer letters. 161. 63-71 (2000)
[Publications] K.Ohtani, et al.: "Follicle-stimulating hormone promotes the growth of human epithelial ovarian cancer cells through the protein Kinase C-mediated system."Cancer letters. (in press). (2001)
[Publications] M.Hattori, et al.: "DNA demethylase is expressed in ovarian cancers and expression correlates with demethylation of CpG sites in the promoter region of c-erbB2 and survivin gene."Cancer letters. (in press). (2001)
[Publications] M.Hattori, et al.: "DNA demethylase expression correlates with lung resistance protein expression in common epithelial ovarian cancers."Journal of International Medical Research. (in press). (2001)

2000 Fiscal Year Annual Research Report

子宮体癌における腫瘍ワクチン開発の基礎的研究(副題:c-erbB2をコードするfusion geneを含んだplasmid DNAを用いた腫瘍ワクチンの開発)

Principal Investigator

佐藤 和雄 日本大学, 医学部, 教授 (80010180)

Research Products

[Publications] H.Sakamoto, et al: "Thymidine phosphorylase expression is predominantly observed in stroma of well-differentiated adenocarcinoma of endometrium and correlates with a frequentcy of vascular involvement"Gynecologic Oncology. 72. 298-305 (1999)

[Publications] H.Sakamoto, et al.: "Gene expression in primary, metastatic and recurrent lesions of endometrial cancer."Gynecol gic and Obstet ric Investigation. 192. 1-11 (1999)

[Publications] K.Ohtani, et al.: "Ezrin, a membrane-cytoskeletal linking protein, is involved in the process of invasion of endometrial cancer cells."Cancer letters. 144. 1-8 (1999)

[Publications] K.Kinoshita, et al.: "Steroid hormone receptors and multi-drug resistant genes expression in gynecologic cancers."Nihon University Journal of Medicine. 41. 1-14 (1999)

[Publications] K.Ohtani, et al.: "Molecular pathogenesis of endometrial hyperplasia and adenocarcinoma."Nihon University Journal of Medicine. 41. 181-193 (1999)

[Publications] Y.Nakayama, et al.: "Tamoxifen and gonadal steroids inhibit colon cancer growth, thymidylate synthase, survivin and telomerase expression through estrogen receptor beta mediated system."Nihon University Journal of Medicine. 42. 137-150 (2000)

[Publications] Y.Nakayama, et al.: "Tamoxifen and gonadae steroids inhibit colon cancer growth is association with inhibition of thymidylate synthase, survivin and telomerase expression through estrogen receptor beta mediated system."Cancer letters. 161. 63-71 (2000)

[Publications] K.Ohtani, et al.: "Follicle-stimulating hormone promotes the growth of human epithelial ovarian cancer cells through the protein Kinase C-mediated system."Cancer letters. (in press). (2001)

[Publications] M.Hattori, et al.: "DNA demethylase is expressed in ovarian cancers and expression correlates with demethylation of CpG sites in the promoter region of c-erbB2 and survivin gene."Cancer letters. (in press). (2001)

[Publications] M.Hattori, et al.: "DNA demethylase expression correlates with lung resistance protein expression in common epithelial ovarian cancers."Journal of International Medical Research. (in press). (2001)

佐藤和雄日本大学, 医学部, 教授 (80010180)