Development of vector specific to diffuse-type gastric cancer cells for peritoneal metastasis control

• Project/Area Number: 23501322
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Clinical oncology
• Research Institution: National Center of Neurology and Psychiatry
• Principal Investigator: SASAKI Hiroki 独立行政法人国立がん研究センター, 研究所, ユニット長 (60235265)
• Co-Investigator(Kenkyū-buntansha): SAEKI Norihisa 独立行政法人国立がん研究センター, 研究所, 主任研究員 (80466200)
• Project Period (FY): 2011 – 2013
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2012: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2011: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 遺伝子治療 / びまん型胃がん / 胃がん / 癌

Research Abstract

We investigated the promoter activity of the GSDMB gene, which was identified to be expressed preferentially in diffuse-type gastric cancers (GCs). This promoter was found to act weakly in human mesothelial cell line MeT-5A but strongly in 5 of 6 diffuse-type GC cell lines. We next constructed the GSDMB promoter-driven HSVtk-lentivirus vector. This vector showed no cytotoxicity in MeT-5A cells, whereas 70% of diffuse-type GC-derived 60As6 cells were killed by Ganciclovir (GCV) treatment. We then established a peritoneal-metastasis control mouse model using 60As6 cells. By GCV treatment only once a week for 30 days after i.p. of 106 60As6 cells, we evaluated in vivo effects of this vector. The survival rate of GCV-treated mice showed 67%, but that of control mice showed 33%.

Research Products

• [Journal Article] MicroRNA-148a is downregulated in gastric cancer, targets MMP7, and indicates tumor invasiveness and poor prognosis (2014)
  • Author(s): Sakamoto N, Naito Y, Oue N, Sentani K, Uraoka N, Zarni Oo H, Yanagihara K, Aoyagi K, Sasaki H, Yasui W
  • Journal Title: Cancer Sci. Volume: 105 Pages: 236-243
  • Peer Reviewed
• [Journal Article] Human subperitoneal fibroblast and cancer cell interaction creates microenvironment that enhances tumor progression and metastasis (2014)
  • Author(s): Kojima M, Higuchi Y, Yokota M, Ishii G, Saito N, Aoyagi K, Sasaki H, Ochiai A
  • Journal Title: PLoS One Volume: 9
  • Peer Reviewed
• [Journal Article] Gene expression signatures for identifying diffuse-type gastric cancer associated with epithelial-mesenchymal transition (2014)
  • Author(s): Tanabe S, Aoyagi K, Yokozaki H, Sasaki H
  • Journal Title: Int. J. Oncol Volume: 44 Pages: 1955-1970
  • Peer Reviewed
• [Journal Article] Intraperitoneal delivery of a small interfering RNA targeting NEDD1 prolongs the survival of scirrhous gastric cancer model mice (2013)
  • Author(s): Fujita T, Yanagihara K, Takeshita F, Aoyagi K, Takigahira M, Chiwaki F, Fukagawa T, Katai H, Ochiya T, Sakamoto H, Konno H, Yoshida T, Sasaki H
  • Journal Title: Cancer Sci. Volume: 104 Pages: 214-222
  • Peer Reviewed
• [Journal Article] Technical consideration for analyzing EMT-MET data from surgical samples (2013)
  • Author(s): Aoyagi K, Tamaoki M, Nishimura T, Sasaki H
  • Journal Title: Cancer Lett.
  • Peer Reviewed
• [Journal Article] Classification of gastric cancer subtypes using ICA, MLR and Bayesian network (2013)
  • Author(s): Ishii H, Sasaki H, Aoyagi K, Yamazaki T
  • Journal Title: Stud. Health Technol. Inform.
  • Peer Reviewed
• [Journal Article] Intraperitoneal delivery of a small interfering RNA targeting NEDD1 prolongs the survival of scirrhous gastric cancer model mice (2013)
  • Author(s): Fujita T, Yanagihara K, Takeshita F,他 11人
  • Journal Title: Cancer Sci. Volume: 104 Issue: 2 Pages: 214
  • DOI: 10.1111/cas.12054
  • URL: https://pure.teikyo.jp/en/publications/79240a16-173f-4a41-b360-91f6aa299c70
  • Peer Reviewed
• [Journal Article] Analysis for thecombination expression of CK20, FABP1, and MUC2 is sensitive for the prediction of peritoneal recurrence in gastric cancer (2012)
  • Author(s): Satoh Y, Mori K, Kitano K, Kitayama J, Yokota H, Sasaki H, Uozaki H, Fukayama M, Seto M, Nagawa H, Yatomi Y, Takai D
  • Journal Title: Jpn. J. Clin. Oncol. Volume: 42 Pages: 148-152
  • Peer Reviewed
• [Journal Article] FGFR2 gene amplification and clinicopathological features in gastric cancer (2012)
  • Author(s): Matsumoto K, Arao T, Hamaguchi T, Shimada Y, Kato K, Ichiro Oda I, Taniguchi H, Koizumi F, Yanagihara K, Sasaki H, Nishio K, Yamada Y
  • Journal Title: Br. J. Cancer Volume: 106 Pages: 727-732
  • Peer Reviewed
• [Journal Article] Upregulation of HOXA10 in gastric cancer with intestinal mucin phenotype : reduction during tumor progression and favorable prognosis (2012)
  • Author(s): Sentani K, Oue N, Naito Y, Sakamoto N, Anami K, Oo HZ, Uraoka N, Aoyagi K, Sasaki H, Yasui W
  • Journal Title: Carcinogenesis Volume: 33 Pages: 1081-1088
  • NAID: 120005308208
  • Peer Reviewed
• [Journal Article] Mesenchymal stem cells provide an advantageous tumor microenvironment for the restoration of cancer stem cells (2012)
  • Author(s): Nishimura K, Semba S, Aoyagi K, Sasaki H, Yokozaki H
  • Journal Title: Pathobiology Volume: 79 Pages: 290-306
  • Peer Reviewed
• [Journal Article] Changes in the melanocortin receptors in the hypothalamus of a rat model of cancer cachexia (2012)
  • Author(s): Suzuki M, Narita M, Ashikawa M, Furuta S, Matoba M, Sasaki H, Yanagihara K, Terawaki K Suzuki T, Uezono Y
  • Journal Title: Synapse Volume: 66 Pages: 747-751
  • Peer Reviewed
• [Journal Article] Sensation of abdominal pain induced by peritoneal carcinomatosis is accompanied by changes in the expression of substance P and m-opioid receptors in the spinal cord of mice (2012)
  • Author(s): Suzuki M, Narita M, Hasegawa M, Furuta S, Kawamata T, Miyano K, Yanagihara K, Chiwaki F, Ochiya T, Suzuki T, Matoba M, Sasaki H, Uezono Y
  • Journal Title: Anesthesiology Volume: 117 Pages: 847-856
  • Peer Reviewed
• [Journal Article] Liver-intestine cadherin induction by epidermal growth factor receptor is associated with intestinal differentiation of gastric cancer (2012)
  • Author(s): Sakamoto N, Oue N, Sentani K, Anami K, Uraoka N, Naito Y, Oo HZ, Ohdan H, Yanagihara K, Aoyagi K, SasakiH, Yasui W
  • Journal Title: Cancer Sci. Volume: 103 Pages: 1744-1750
  • Peer Reviewed
• [Journal Article] RegIV is a direct target of intestinal transcription factor CDX2 in gastric cancer (2012)
  • Author(s): Naito Y, Oue N, Hinoi T, Sakamoto N, Sentani K, Ohdan H, Yanagihara K, Sasaki H, Yasui W
  • Journal Title: PLoS One Volume: 7
  • Peer Reviewed
• [Journal Article] Chromosome 1q22 is a susceptibility locus of diffuse-type gastric cancer, harboring a functional SNP of MUC1 (2011)
  • Author(s): Saeki N, Saito A, Choi JI, Matsuno K, Ohnami S, Totsuka H, Chiku S, Kuchiba A, Lee Y-S, Yoon K-A, Kook M-C, Park SR, Kim Y-W, Tanaka H, Tajima K, Hirose H, Tanioka F, Matsuno Y, Sugimura H, Kato S, Nakamura T, Nishina T, Yasui W, Aoyagi K, Sasaki H, Yanagihara K, Katai H, Shimoda T, Yoshida T, Nakamura Y, Hirohashi S, Sakamoto H
  • Journal Title: Gastroenterology Volume: 140 Pages: 892-902
  • Peer Reviewed
• [Journal Article] Artificially induced epithelial-mesenchymal transition in surgicasl subjects : its implications in clinical and basic cancer research (2011)
  • Author(s): Aoyagi K, Minashi K, Igaki H, Tachimori Y, Nishimura T, Hokamura N, Ashida A, Daiko H, Ochiai A, Muto M, Ohtsu A, Yoshida T, Sasaki H
  • Journal Title: PLoS One Volume: 6(4)
  • Peer Reviewed
• [Journal Article] Signal peptidase complex 18, encoded by SEC11A, contributes to progression via TGF-a secretion in gastric cancer
  • Author(s): Oue N, Naito Y, Hayashi T, Takigahira M, Kawano-Nagatsuma A, Sentani K, Sakamoto N, Zarni Oo H, Uraoka N, Yanagihara K, Ochiai A, Sasaki H, Yasi W
  • Journal Title: Oncogene Volume: (in press)
  • Peer Reviewed
• [Presentation] Gene combination regulated in stem cells and gastric cancer cells (2013)
  • Author(s): Shihori Tanabe, Kazuhiko Aoyagi, Hiroshi Yokozaki, Hiroki Sasaki
  • Organizer: Ninth AACR-JCA Joint Conference
• [Presentation] 胃がん細胞と間葉系幹細胞において発現変化する遺伝子群 (2013)
  • Author(s): 田邊思帆里、青柳一彦、横崎宏、佐々木博己
  • Organizer: 第133回日本薬学会
• [Presentation] 胃がん細胞と間葉系幹細胞の遺伝子発現変動解析による細胞の性質判定マーカーの同定 (2013)
  • Author(s): 田邊思帆里、青柳一彦、横崎宏、佐々木博己
  • Organizer: 第40回日本毒性学会
• [Presentation] オピオイド増殖因子シグナル阻害によるドセタキセルの抗腫瘍作用の増強効果 (2013)
  • Author(s): 鈴木雅美、千脇史子、澤田祐美、成田年、鈴木 勉、長瀬 博、上園保仁、佐々木博己
  • Organizer: 第33回鎮痛薬・オピオイドペプチドシンポジウム
• [Presentation] オピオイド増殖因子シグナルの阻害は細胞周期のRecycling によって胃癌細胞へのドセタキセルの抗腫瘍効果を増強する (2013)
  • Author(s): 鈴木雅美、千脇史子、澤田祐美、柳原吾吉、中釜斉、上園保仁、佐々木博己
  • Organizer: 第72回日本癌学会
• [Presentation] 腸型粘液形質胃癌で多く発現するHOXA10 は予後良好因子である (2013)
  • Author(s): 仙谷和弘、大上直秀、内藤寛、坂本直也、Htoo Zarni Oo、浦岡直礼、青柳一彦、佐々木博己、安井弥
  • Organizer: 第72回日本癌学会
• [Presentation] マウス腹膜中皮細胞とヒト未分化型胃がん細胞の異種間細胞相互作用系の評価 (2013)
  • Author(s): 千脇史子、鈴木雅美、澤田祐美、浜口哲弥、山田康秀、島田安博、柳原五吉、坂本裕美、松崎圭祐、上園保仁、吉田輝彦、佐々木博己
  • Organizer: 第72回日本癌学会
• [Presentation] MiR-148a, down-regulated in gastric cancer, targets MMP7 and participates in tumor invasion and poor prognosis (2013)
  • Author(s): Naoya Sakamoto, Yutaka Naito, Naohide Oue, Kazuhiro Sentani, Naohiro Uraoka, Htoo Zarni Oo, Kazuyoshi Yanagihara, Kazuhiko Aoyagi, Hiroki Sasaki, Wataru Yasui
  • Organizer: The 11^<th> ICGC
• [Presentation] Transforming growth factor-b enhances the effect of docetaxel via inducing asymmetric cell division of CXCR4^+ gastric cancer stem cells in a dormant state (2013)
  • Author(s): Takeshi Fujita, Fumiko Chiwaki, Ryo-u Takahashi, Kazuyoshi Yanagihara, Kazuhiko Aoyagi, Hiromi Sakamoto, Takeo Fukagawa, Hitoshi Katai, Takahiro Ochiya, Manabu Ohta, Kinji Kamiya, Hiroyuki Konno, Teruhiko Yoshida, Hiroki Sasaki
  • Organizer: The 4^<th> JCA-AACR Special Joint Conference
• [Presentation] Towards the genetics and genomics of diffuse gastric cancer (2013)
  • Author(s): Hiromi Sakamoto, Norihisa Saeki, Hidemi Itoh, Keitaro Matsuo, Hidetaka Yamada, Haruhiko Sugimura, Hitoshi Ichikawa, Hiroki Sasaki, Teruhiko Yoshida
  • Organizer: The 4^<th> JCA-AACR Special Joint Conference
• [Presentation] 癌性腹膜炎疼痛モデルマウスの脊髄における□-opioid受容体およびサブスタンスP の発現変化 (2012)
  • Author(s): 芦川真帆、鈴木雅美、 成田 年、 長谷川実奈美、 鈴木 勉、 的場元弘、 佐々木博己、 上園保仁
  • Organizer: 第85回日本薬理学会年会
• [Presentation] びまん性胃癌で特異的に発現するプロテアーゼの探索 (2012)
  • Author(s): 藤田剛、青柳一彦、柳原五吉、佐々木博己、今野弘之
  • Organizer: 第17回日本病態プロテアーゼ学会
• [Presentation] 腹膜播種におけるびまん性胃癌幹細胞に対するTGF-beta の二元的機能 (2012)
  • Author(s): 藤田剛、高橋陵宇、千脇史子、柳原五吉、青柳一彦、坂本裕美、深川剛生、片井均、落谷孝広、今野弘之、吉田輝彦、佐々木博己
  • Organizer: 第71回日本癌学会、ワークショップ
• [Presentation] 未分化胃がん患者腹水からの新規34 がん細胞株および2 マウス中皮細胞株の樹立 (2012)
  • Author(s): 千脇史子、浜口哲弥、山田康秀、島田安博、柳原五吉、坂本裕美、吉田輝彦、佐々木博己
  • Organizer: 第71回日本癌学会
• [Presentation] 胃がんにおけるFGFR2 遺伝子増幅の検討 (2012)
  • Author(s): 松本和子、荒尾徳三、浜口哲弥、島田安博、加藤健、小田一郎、谷口浩和、小泉史明、柳原五吉、佐々木博己、西尾和人、山田康秀
  • Organizer: 第71回日本癌学会、ワークショップ
• [Presentation] 胃がんリンパ節転移に関わるタンパク質の同定 (2012)
  • Author(s): 市川寛、神田達夫、谷口浩和、畠山勝義、佐々木博己、近藤格
  • Organizer: 第71回日本癌学会
• [Presentation] 体外診断薬としての発現解析型DNA チップ (2012)
  • Author(s): 佐々木博己
  • Organizer: 第32回日本分子腫瘍マーカー研究会、特別企画
• [Presentation] Subtyping and recurrence/prognosis prediction of gastric and esophageal cancers by the use of DNA chip (2011)
  • Author(s): Sasaki H
  • Organizer: The 9th Annual Meeting of JSMO
• [Presentation] Multi-marker based RT-PCR for peritoneal cytology of gastric cancverMulti-marker based RT-PCR for peritoneal cytology of gastric cancver (2011)
  • Author(s): Mori K, Sato Y, Kitayama J, Kaizaki S, Ishigami H, Yamaguchi H, Shimizu N, Nomura S, Wada I, Yokota H, Kageyama Y, Sasaki H, Uozaki M, Fukayama M, Yatomi Y, Takai D, Seto M
  • Organizer: The 9th IGCC(Kerea)
• [Presentation] びまん性胃癌における癌幹細胞の同定とその特性 (2011)
  • Author(s): 藤田剛、高橋陵宇、千脇史子、柳原五吉、青柳一彦、坂本裕美、深川剛生、片井均、落谷孝広、今野弘之、吉田輝彦、佐々木博己
  • Organizer: 第70回日本癌学会、ワークショップ
• [Presentation] マイクロアレイによる幹細胞及びがん細胞の発現遺伝子解析 (2011)
  • Author(s): 田邊思帆里、佐々木博己、青柳一彦、横崎宏、鈴木孝昌
  • Organizer: 第70回日本癌学会
• [Presentation] 胃がんのゲノム網羅的遺伝素因の探索 (2011)
  • Author(s): 坂本裕美、佐伯宣久、斎藤聡、松尾恵太郎、佐々木博己、大浪澄子、小野弘恵、片井均、椙村春彦、吉田輝彦
  • Organizer: 第70回日本癌学会、シンポジウム
• [Presentation] 胃がんのゲノム網羅的関連解析 (2011)
  • Author(s): 吉田輝彦、佐伯宣久、斎藤聡、松尾恵太郎、佐々木博己、大浪澄子、小野弘恵、坂本裕美、片井均
  • Organizer: 第70回日本癌学会、シンポジウム
• [Book] Gasdermin superfamily : a novel gene family fuctioning in epithelial cells. In Endothelium and Epithelium : Composition and Functions. (Carrasco J and Mota M (edits)) (2012)
  • Author(s): Saeki N, Sasaki H
  • Publisher: Nova Science
• [Book] EMT と食道扁平上皮癌、Surgery Frontier 19 (2012)
  • Author(s): 佐々木博己、五十畑則之、西村公男、玉置将司、小松崎理絵、千脇史子、青柳一彦
• [Book] 胃がんの予後予測因子、総合臨床、60 (2011)
  • Author(s): 深川剛生、阪真、三森功士、佐々木博己、森田信司、石田道拡、片井均
• [Book] がん幹細胞を標的としたHedgehog シグナル阻害薬、Mebio 28 (2011)
  • Author(s): 佐々木博己、西村公男、小松崎理絵、千脇史子、青柳一彦、山田康秀