Does Autotaxin promote pancreatic cancer?

• Project/Area Number: 17K09466
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Nagoya City University
• Principal Investigator: Yoshida Michihiro 名古屋市立大学, 医薬学総合研究院(医学), 講師 (20636328)
• Co-Investigator(Kenkyū-buntansha): 内藤 格 名古屋市立大学, 医薬学総合研究院(医学), 講師 (30527750) ; 志村 貴也 名古屋市立大学, 医薬学総合研究院(医学), 講師 (90405192)
• Project Period (FY): 2017-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: オートタキシン / 膵癌 / 分子標的治療 / 腹膜播種 / 腹膜播種モデル / オートタキシン阻害剤 / 動物実験 / 血中濃度測定 / オートタキシン阻害薬の膵癌増殖への影響 / 膵臓癌 / 新規分子標的

Outline of Final Research Achievements

Peritoneal dissemination and malignant ascites in pancreatic ductal adenocarcinoma (PDAC) patients represent a major clinical issue. Lysophosphatidic acid (LPA) is a lipid mediator that modulates the progression of various cancers. Based on the increasing evidence showing that LPA is abundant in malignant ascites, we focused on autotaxin (ATX), which is a secreted enzyme that is important for the production of LPA. This study aimed to elucidate the importance of the ATX-LPA axis in malignant ascites in PDAC and to determine whether ATX works as a molecular target for treating peritoneal dissemination. Many findings obtained through this study demonstrated that ATX in ascites works as a promotor of peritoneal dissemination, and the targeting of ATX must represent a useful and novel therapy for peritoneal dissemination of PDAC.

Academic Significance and Societal Importance of the Research Achievements

最も予後不良な癌腫である膵癌に対し、今回の研究を通じてオートタキシンの新たなバイオマーカーおよび治療ターゲットとしての可能性を解明した。今回の研究期間中に抗癌剤耐性獲得に対する貢献も明らかとなっており、今後この分野でのさらなる研究の推進により、オートタキシン・LPAを中心に、臨床応用に直結するような新たな治療薬の誕生に期待したい。

Research Products

• [Journal Article] Endoscopic ultrasound-guided jejunojejunostomy with rendezvous contrast-filling assistance in afferent limb syndrome. (2021)
  • Author(s): Yoshida M, Imafuji H, Hayashi K, Naitoh I, Hori Y, Kato A, Matsuo Y.
  • Journal Title: Endoscopy Volume: - Issue: 02 Pages: E49-E50
  • DOI: 10.1055/a-1348-0707
  • Peer Reviewed / Open Access
• [Journal Article] Four-Step Classification of Endoscopic Transpapillary Gallbladder Drainage and the Practical Efficacy of Cholangioscopic Assistance. (2021)
  • Author(s): Yoshida M, Naitoh I, Hayashi K, Jinno N, Hori Y, Natsume M, Kato A, Kachi K, Asano G, Atsuta N, Sahashi H, Kataoka H.
  • Journal Title: Gut Liver Volume: - Issue: 3 Pages: 476-485
  • DOI: 10.5009/gnl20238
  • Peer Reviewed / Open Access
• [Journal Article] Autotaxin in ascites promotes peritoneal dissemination in pancreatic cancer. (2021)
  • Author(s): Jinno N, Yoshida M, Hayashi K, Naitoh I, Hori Y, Natsume M, Kato A, Kachi K, Asano G, Atsuta N, Sahashi H, Kataoka H
  • Journal Title: Cancer Sci Volume: 112 Issue: 2 Pages: 668-678
  • DOI: 10.1111/cas.14689
  • Peer Reviewed / Open Access
• [Journal Article] Metachronous Pancreatic Ductal Adenocarcinoma with Adjacent Serous Cystadenoma that Was Preoperatively Diagnosed by EUS-FNA: A Case Report and Review of the Literature (2020)
  • Author(s): Yoshida Michihiro、Naitoh Itaru、Hayashi Kazuki、Jinno Naruomi、Natsume Makoto、Hori Yasuki、Kato Akihisa、Kachi Kenta、Asano Go、Matsuo Yoichi、Takahashi Satoru、Kataoka Hiromi
  • Journal Title: Internal Medicine Volume: 59 Issue: 5 Pages: 649-656
  • DOI: 10.2169/internalmedicine.3912-19
  • NAID: 130007804594
  • ISSN: 0918-2918, 1349-7235
  • Year and Date: 2020-03-01
  • Peer Reviewed / Open Access
• [Journal Article] Practical Experiences of Unsuccessful Hemostasis with Covered Self-Expandable Metal Stent Placement for Post-Endoscopic Sphincterotomy Bleeding. (2020)
  • Author(s): Yoshida M, Inoue T, Naitoh I, Hayashi K, Hori Y, Natsume M, Atsuta N, Kataoka H
  • Journal Title: Clin Endosc. Volume: - Issue: 1 Pages: 150-155
  • DOI: 10.5946/ce.2020.217
  • Peer Reviewed / Open Access
• [Journal Article] Laterally Spreading Adenocarcinoma Involving the Lower Bile Duct and Duodenum Expressing Heterogeneous Immunohistochemical Phenotypes (2019)
  • Author(s): Miyabe K, Notohara K, Asano G, Kachi K, Kato A, Natsume M, Jinno N, Hori Y, Yoshida M, Naitoh I, Hayashi K, Ohara H, Takahashi S, Kataoka H.
  • Journal Title: Internal Medicine Volume: 58 Issue: 21 Pages: 3087-3092
  • DOI: 10.2169/internalmedicine.2801-19
  • NAID: 130007740777
  • ISSN: 0918-2918, 1349-7235
  • Year and Date: 2019-11-01
  • Peer Reviewed / Open Access
• [Journal Article] Endoscopic drainage using a lumen-apposing metal stent under contrast-enhanced harmonic endoscopic ultrasonography guidance. (2019)
  • Author(s): Hori Y, Yoshida M, Hayashi K, Naitoh I, Kato A, Miyabe K, Kataoka H.
  • Journal Title: Endoscopy Volume: 51 Issue: 07 Pages: 187-188
  • DOI: 10.1055/a-0875-3546
  • Peer Reviewed / Open Access
• [Journal Article] Pancreatic stone extraction using a pancreatoscopy-directed, thin-sheathed basket catheter. (2019)
  • Author(s): Miyabe K, Yoshida M, Hayashi K.
  • Journal Title: Dig Endosc Volume: - Issue: 1
  • DOI: 10.1111/den.13405
  • Peer Reviewed / Open Access
• [Journal Article] Successful peroral endoscopic removal of migrated metal stent. (2019)
  • Author(s): Hori Y, Hayashi K, Sobajima Y, Naitoh I, Miyabe K, Yoshida M, Kataoka H.
  • Journal Title: Endoscopy Volume: 51 Issue: 11 Pages: 339-340
  • DOI: 10.1055/a-0915-1756
  • Peer Reviewed / Open Access
• [Journal Article] Successful endoscopic transpapillary gallbladder stenting using a new easily maneuverable guidewire: a report of two cases. (2019)
  • Author(s): Miyabe K, Kato A, Asano G, Hori Y, Yoshida M, Naitoh I, Hayashi K.
  • Journal Title: Endoscopy Volume: 51 Issue: 11 Pages: 349-351
  • DOI: 10.1055/a-0929-4645
  • Peer Reviewed / Open Access
• [Journal Article] Novel technique for intraductal cholangioscopy-assisted biliary drainage with over-the-wire microcatheter manipulation. (2019)
  • Author(s): Yoshida M, Kato A, Hayashi K, Naitoh I, Miyabe K, Hori Y, Asano G.
  • Journal Title: Endoscopy Volume: 51 Issue: 12 Pages: 398-399
  • DOI: 10.1055/a-0962-9628
  • Peer Reviewed / Open Access
• [Journal Article] Predictive factors for the mortality of acute pancreatitis on admission. (2019)
  • Author(s): Jinno N, Hori Y, Naitoh I, Miyabe K, Yoshida M, Natsume M, Kato A, Asano G, Sano H, Hayashi K.
  • Journal Title: PLoS One Volume: 14 Issue: 8 Pages: e0221468-e0221468
  • DOI: 10.1371/journal.pone.0221468
  • Peer Reviewed / Open Access
• [Journal Article] Prophylactic technique for preventing inward stent migration during placement of multiple plastic stents in a patient with surgically altered anatomy. (2019)
  • Author(s): Kachi K, Hori Y, Hayashi K, Naitoh I, Yoshida M, Kataoka H.
  • Journal Title: Endoscopy Volume: 52 Issue: 03 Pages: 234-235
  • DOI: 10.1055/a-1012-1709
  • Peer Reviewed / Open Access
• [Journal Article] On-and-off deployment technique of a lumen-apposing metal stent during endoscopic pancreatic necrosectomy (2019)
  • Author(s): Yoshida Michihiro、Naitoh Itaru、Yamada Ruriko、Hayashi Kazuki、Natsume Makoto、Hori Yasuki、Kataoka Hiromi
  • Journal Title: Endoscopy Volume: 52 Issue: 05 Pages: 158-159
  • DOI: 10.1055/a-1046-1513
  • Peer Reviewed / Open Access
• [Journal Article] Autoimmune Hemolytic Anemia Obscured by the Obstructive Jaundice Associated with IgG4-related Sclerosing Cholangitis in a Patient with Type 1 Autoimmune Pancreatitis: A Case Report and Review of the Literature (2018)
  • Author(s): Yoshida M, Marumo Y, Naitoh I, Hayashi K, Miyabe K, Nishi Y, Fujita Y, Jinno N, Hori Y, Natsume M, Kato A, Iida S, Joh T.
  • Journal Title: Internal Medicine Volume: 57 Issue: 12 Pages: 1725-1732
  • DOI: 10.2169/internalmedicine.9818-17
  • NAID: 130007397141
  • ISSN: 0918-2918, 1349-7235
  • Year and Date: 2018-06-15
  • Peer Reviewed / Open Access
• [Journal Article] The absence of class III β-tubulin is predictive of a favorable response to nab-paclitaxel and gemcitabine in patients with unresectable pancreatic ductal adenocarcinoma. (2018)
  • Author(s): Kato A, Naiki-Ito A, Naitoh I, Hayashi K, Nakazawa T, Shimizu S, Nishi Y, Okumura F, Tadahisa I, Takada H, Kondo H, Yoshida M, Takahashi S, Joh T.
  • Journal Title: Hum Pathol Volume: 74 Pages: 92-98
  • DOI: 10.1016/j.humpath.2018.01.009
  • Peer Reviewed / Open Access
• [Journal Article] Differential diagnosis of cholangiocarcinoma and IgG4-related sclerosing cholangitis by fluorescence in?situ hybridization using transpapillary forceps biopsy specimens (2018)
  • Author(s): Kato Akihisa、Naitoh Itaru、Miyabe Katsuyuki、Hayashi Kazuki、Kondo Hiromu、Yoshida Michihiro、Kato Hiroyuki、Kuno Toshiya、Takahashi Satoru、Joh Takashi
  • Journal Title: Journal of hepato-billiary pancreatic sciences Volume: 25 Issue: 3 Pages: 188-194
  • DOI: 10.1002/jhbp.536
  • Peer Reviewed / Open Access
• [Journal Article] An Increased Chromosome 7 Copy Number in Endoscopic Bile Duct Biopsy Specimens Is Predictive of a Poor Prognosis in Cholangiocarcinoma. (2018)
  • Author(s): Kato A, Naitoh I, Miyabe K, Hayashi K, Yoshida M, Hori Y, Natsume M, Jinno N, Asano G, Kato H, Kuno T, Takahashi S, Kataoka H.
  • Journal Title: Dig Dis Sci. Volume: 63(12) Issue: 12 Pages: 3376-3381
  • DOI: 10.1007/s10620-018-5280-4
  • Peer Reviewed / Open Access
• [Journal Article] Recanalization of postoperative biliary disconnection with intraductal cholangioscopy-assisted forceps retrieval of rendezvous guidewire. (2018)
  • Author(s): Yoshida M, Morimoto M, Kato A, Hayashi K, Naitoh I, Miyabe K, Matsuo Y.
  • Journal Title: Endoscopy Volume: 50 Issue: 12 Pages: E338-E339
  • DOI: 10.1055/a-0667-7751
  • Peer Reviewed / Open Access
• [Journal Article] The utility and efficacy of self-expandable metal stents for treating malignant gastric outlet obstructions in patients under best supportive care. (2018)
  • Author(s): Hori Y, Naitoh I, Hayashi K, Miyabe K, Yoshida M, Fujita Y, Natsume M, Jinno N, Kato A, Nakazawa T, Shimizu S, Hirano A, Okumura F, Ando T, Sano H, Takada H, Togawa S, Joh T.
  • Journal Title: Support Care Cancer Volume: 26 Issue: 10 Pages: 3587-3592
  • DOI: 10.1007/s00520-018-4221-2
  • Peer Reviewed / Open Access
• [Journal Article] Covered duodenal self-expandable metal stents prolong biliary stent patency in double stenting: The largest series of bilioduodenal obstruction. (2018)
  • Author(s): Hori Y, Naitoh I, Hayashi K, Kondo H, Yoshida M, Shimizu S, Hirano A, Okumura F, Ando T, Jinno N, Takada H, Togawa S, Joh T.
  • Journal Title: J Gastroenterol Hepatol Volume: 33 Issue: 3 Pages: 696-703
  • DOI: 10.1111/jgh.13977
  • Peer Reviewed / Open Access
• [Journal Article] Maltotriose conjugated to a chlorin derivative enhances the antitumor effects of photodynamic therapy in peritoneal dissemination of pancreatic cancer. (2017)
  • Author(s): Kato A, Kataoka H, Yano S, Hayashi K, Hayashi N, Tanaka M, Naitoh I, Ban T, Miyabe K, Kondo H, Yoshida M, Fujita Y, Hori Y, Natsume M, Murakami T, Narumi A, Nomoto A, Naiki-Ito A, Takahashi S, Joh T
  • Journal Title: Mol Cnacer Ther Volume: 印刷中 Issue: 6 Pages: 1124-1132
  • DOI: 10.1158/1535-7163.mct-16-0670
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Novel characteristics of traction force in biliary self-expandable metallic stents. (2016)
  • Author(s): Hori Y, Hayashi K, Yoshida M, Naitoh I, Ban T, Miyabe K, Kondo H, Nishi Y, Umemura S, Fujita Y, Natsume M, Kato A, Ohara H, Joh T.
  • Journal Title: Dig Endosc Volume: 印刷中 Issue: 3 Pages: 347-352
  • DOI: 10.1111/den.12796
  • Peer Reviewed / Open Access
• [Presentation] Autotaxin in ascites is a potential target for cancerous peritoneal dissemination in pancreatic cancer (2021)
  • Author(s): Naruomi Jinno, Michihiro Yoshida, Akihisa Kato, Makoto Natsume, Hiromi Kataoka
  • Organizer: 第79回日本癌学会学術総会
  • Int'l Joint Research
• [Presentation] 内視鏡的経乳頭胆嚢ドレナージ（ETGBD)困難例に対するSpyGlass DSを用いた胆嚢管選択の有用性 (2019)
  • Author(s): 吉田道弘、林香月、内藤格
  • Organizer: 第９７回日本消化器内視鏡学会総会
• [Presentation] 膵頭部SCN長期経過観察中に閉塞性黄疸を発症し発見された漿液性嚢胞腺腫併存膵癌の１例 (2019)
  • Author(s): 吉田道弘、林香月、内藤格、宮部勝之、堀寧、神野成臣、夏目まこと、加地謙太、浅野剛、斎藤健太、松尾洋一、片岡洋望
  • Organizer: 第５０回日本膵臓学会大会
• [Presentation] 内視鏡的胆道ドレナージ困難例におけるマイクロカテーテルを用いたSpyGlass DS下選択的ガイディング法の有用性 (2019)
  • Author(s): 吉田道弘、林香月、内藤格、堀寧、神野成臣、夏目まこと、加地謙太、浅野剛、片岡洋望
  • Organizer: 第５６回日本胆道学会学術集会
• [Presentation] 内視鏡的胆道ドレナージ困難例におけるSpyGlass DS下選択的ガイディング法の有用性 (2019)
  • Author(s): 吉田道弘、内藤格、林香月
  • Organizer: JDDW2019
• [Presentation] 安全性・成功率向上を目指した内視鏡的経乳頭的胆嚢ドレナージ（ETGBD)の新たな試みーSpyGlass DSを用いた胆嚢管アプローチ法の有用性 (2019)
  • Author(s): 吉田道弘、内藤格、林香月
  • Organizer: 第62回日本消化器内視鏡学会東海支部例会
• [Presentation] Autotaxin inhibition suppresses colon cancer growth and metastasis (2018)
  • Author(s): Michihiro Yoshida
  • Organizer: 日本癌学会総会
  • Int'l Joint Research
• [Presentation] 当院におけるSpyGlass DS胆管内手技－狙撃生検・砕石・ドレナージ－の検討：内視鏡診断・治療への貢献 (2018)
  • Author(s): 吉田 道弘
  • Organizer: JDDW2018
• [Presentation] 難治性総胆管結石におけるSpyGlass DS適正使用の検討―EPLBD下治療困難例の解析から (2018)
  • Author(s): 吉田 道弘
  • Organizer: 第61回日本消化器内視鏡学会東海支部例会
• [Presentation] 当院におけるSpyGlass DS使用の現状：診断と治療への貢献 (2018)
  • Author(s): 吉田 道弘
  • Organizer: 日本消化器病学会東海支部第128回例会
• [Presentation] 大腸癌治療におけるオートタキシン(ATX)制御の有用性 (2017)
  • Author(s): 吉田 道弘 林 香月 城 卓志
  • Organizer: 第103回 日本消化器病学会総会