Establishment of the model of intestinal and gastric type gastric cancer using CRISPR/Cas9 and organoid

• Project/Area Number: 16H06999
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Single-year Grants
• Research Field: Experimental pathology
• Research Institution: Hiroshima University
• Principal Investigator: Sakamoto Naoya 広島大学, 医歯薬保健学研究科(医), 助教 (20571798)
• Project Period (FY): 2016-08-26 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000); Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: オルガノイド / CRISPR/Cas9 / ゲノム編集 / 胃がん / 個別化医療 / 癌 / 胃癌 / ゲノム

Outline of Final Research Achievements

We have established the organoids from intestinal metaplasia and fundic/pyloric gland by using the selection of culture condition and FACS, and then try to introduce several genomic abnormalities that are characteristic especially in gastric cancer (GC) using CRISPR/Cas9 system. We also generated the organoids from GC cases with intestinal and gastric mucin phenotype, respectively. It was found that GC organoids with intestinal mucin phenotype showed more significant resistance against 5-FU than GC organoids with gastric mucin phenotype.

Research Products

• [Journal Article] Transcribed ultraconserved region Uc.63+ promotes resistance to docetaxel through regulation of androgen receptor signaling in prostate cancer. (2017)
  • Author(s): Sekino Y, Sakamoto N, Goto K, Honma R, Shigematsu Y, Sentani K, Oue N, Teishima J, Matsubara A and Yasui W
  • Journal Title: Oncotarget Volume: 8 Issue: 55 Pages: 94259-94270
  • DOI: 10.18632/oncotarget.21688
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Overexpression of the Transmembrane Protein IQGAP3 Is Associated with Poor Survival of Patients with Gastric Cancer. (2017)
  • Author(s): Oue N, Yamamoto Y, Oshima T, Asai R, Ishikawa A, Uraoka N, Sakamoto N, Sentani K, Yasui W.
  • Journal Title: Pathobiology Volume: - Issue: 3 Pages: 192-200
  • DOI: 10.1159/000481890
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Overexpression of the transmembrane protein BST-2 induces Akt and Erk phosphorylation in bladder cancer. (2017)
  • Author(s): Shigematsu Y, Oue N, Nishioka Y, Sakamoto N, Sentani K, Sekino Y, Mukai S, Teishima J, Matsubara A, Yasui W.
  • Journal Title: Oncol Lett Volume: 14 Issue: 1 Pages: 999-1004
  • DOI: 10.3892/ol.2017.6230
  • Peer Reviewed / Open Access
• [Journal Article] Overexpression of PCDHB9 promotes peritoneal metastasis and correlates with poor prognosis in patients with gastric cancer. (2017)
  • Author(s): Mukai S, Oue N, Oshima T, Imai T, Sekino Y, Honma R, Sakamoto N, Sentani K, Kuniyasu H, Egi H, Tanabe K, Yoshida K, Ohdan H, Yasui W.
  • Journal Title: J Pathol Volume: 243 Issue: 1 Pages: 100-110
  • DOI: 10.1002/path.4931
  • Peer Reviewed / Open Access
• [Journal Article] The Expression of BTS-2 Enhances Cell Growth and Invasiveness in Renal Cell Carcinoma. (2017)
  • Author(s): Pham QT, Oue N, Yamamoto Y, Shigematsu Y, Sekino Y, Sakamoto N, Sentani K, Uraoka N, Tiwari M, Yasui W
  • Journal Title: Anticancer Research Volume: 37 Pages: 2853-2860
  • Peer Reviewed
• [Journal Article] Expression and function of Uc.160+, a transcribed ultraconserved region, in gastric cancer. (2017)
  • Author(s): Honma R, Goto K, Sakamoto N, Sekino Y, Sentani K, Oue N, Yasui W.
  • Journal Title: Gastric Cancer Volume: 20 Issue: 6 Pages: 960-969
  • DOI: 10.1007/s10120-017-0714-9
  • NAID: 40021377334
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Long-term follow-up study of gastric adenoma; tumor-associated macrophages are associated to carcinoma development in gastric adenoma. (2017)
  • Author(s): Taniyama D, Taniyama K, Kuraoka K, Zaitsu J, Saito A, Nakatsuka H, Sakamoto N, Sentani K, Oue N, Yasui W.
  • Journal Title: Gastric Cancer Volume: 20 Issue: 6 Pages: 929-939
  • DOI: 10.1007/s10120-017-0713-x
  • NAID: 40021377278
  • Peer Reviewed
• [Journal Article] BRAFV600E cooperates with CDX2 inactivation to promote serrated colorectal tumorigenesis. (2017)
  • Author(s): Sakamoto N, Feng Y, Stolfi C, Kurosu Y, Green M, Lin J, Green ME, Sentani K, Yasui W, McMahon M, Hardiman KM, Spence JR, Horita N, Greenson JK, Kuick R, Cho KR, Fearon ER.
  • Journal Title: Elife Volume: 6 Pages: 6-6
  • DOI: 10.7554/elife.20331
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Clinicopathological significance of SPC18 in colorectal cancer: SPC18 participates in tumor progression. (2017)
  • Author(s): Hattori T, Sentani K, Naohide O, Sakamoto N, Yasui W
  • Journal Title: Cancer Science Volume: 108(1) Issue: 1 Pages: 143-150
  • DOI: 10.1111/cas.13121
  • Peer Reviewed / Open Access
• [Journal Article] KIFC1 induces resistance to docetaxel and is associated with survival of prostate cancer patients (2017)
  • Author(s): Sekino Y, Oue N, Shigematsu Y, Ishikawa A, Sakamoto N, Sentani K, Teishima J, Matsubara A, Yasui W
  • Journal Title: Urologic Oncology Volume: 35 Issue: 1 Pages: 13-31
  • DOI: 10.1016/j.urolonc.2016.08.007
  • Peer Reviewed / Open Access
• [Journal Article] KIF11 Is Required for Spheroid Formation by Oesophageal and Colorectal Cancer Cells. (2017)
  • Author(s): Imai T, Oue N, Sentani K, Sakamoto N, Uraoka N, Egi H, Hinoi T, Ohdan H, Yoshida K, Yasui W.
  • Journal Title: Anticancer Research Volume: 37(1) Pages: 47-55
  • Peer Reviewed
• [Journal Article] Characteristic expression of fukutin in gastric cancer among atomic bomb survivors. (2017)
  • Author(s): Pham TT, Oue N, Yamamoto M, Fujihara M, Ishida T, Mukai S, Sakamoto N, Sentani K, Yasui W.
  • Journal Title: Oncology Letter Volume: 13(2) Pages: 937-941
  • Peer Reviewed
• [Journal Article] Induction of KIFC1 expression in gastric cancer spheroids (2016)
  • Author(s): Oue N, Mukai S, Imai T, Trang TBP, Oshima T, Sentani K, Sakamoto N, Yoshida K, Yasui W
  • Journal Title: Oncology Reports Volume: 36 Issue: 1 Pages: 349-355
  • DOI: 10.3892/or.2016.4781
  • Peer Reviewed / Open Access
• [Journal Article] Overexpression of KIF11 in gastric cancer with intestinal mucin phenotype (2016)
  • Author(s): Imai T, Oue N, Nishioka M, Mukai S, Oshima T, Sakamoto N, Sentani K, Matsusaki K, Yoshida K, Yasui W
  • Journal Title: Pathobiology Volume: 84 Issue: 1 Pages: 16-24
  • DOI: 10.1159/000447303
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] The transcribed-ultra conserved regions in prostate and gastric cancer: DNA hypermethylation and microRNA-associated regulation. (2015)
  • Author(s): Keisuke Goto, Sho Ishikawa,Ririno Honma, Keiji Tanimoto, Naoya Sakamoto,Kazuhiro Sentani, Naohide Oue, Jun Teishima, Akio Matsubara and Wataru Yasui.
  • Journal Title: Oncogene Volume: 1 Issue: 27 Pages: 1-1
  • DOI: 10.1038/onc.2015.445
  • Peer Reviewed / Open Access
• [Presentation] Stem cell derived organoid: a promising tool for basic and clinical research (2017)
  • Author(s): Sakamoto Naoya
  • Organizer: Bridging Gaps in Oncology 2017
  • Int'l Joint Research / Invited
• [Presentation] A gastric cancer organoid library provides a hopeful resource for drug screening (2017)
  • Author(s): 本間りりの、坂本直也、石川 洸、仙谷和弘、大上直秀、安井 弥
  • Organizer: 第76回 日本癌学会
• [Presentation] CRISPR/Cas9による胃型・腸型胃がんオルガノイドモデルの樹立及び薬剤感受性の検討 (2017)
  • Author(s): 坂本 直也
  • Organizer: 第28回日本消化器癌発生学会
  • Int'l Joint Research