Cancer stem cell in colorectal liver metastasis

• Project/Area Number: 24592009
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: Yokohama City University
• Principal Investigator: TANAKA Kuniya 横浜市立大学, 医学(系)研究科(研究院), 客員教授 (10295503)
• Co-Investigator(Kenkyū-buntansha): HIRANO Hisashi 横浜市立大学, 生命科学研究科, 特任教授 (00275075) ; HIROSHIMA Yukihiko 横浜市立大学, 医学研究科, 客員研究員 (60718021)
• Project Period (FY): 2012-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000); Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2013: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000); Fiscal Year 2012: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 癌幹細胞 / 大腸癌肝転移 / CD133 / CD44 / E cadherin / 転移性肝癌 / 大腸癌 / 肝転移 / CD13

Outline of Final Research Achievements

The CD44-positive rate in primary lesions and L-Mets was 41.4 and 58.7 %, respectively. There was no correlation of CD44 expression between primary lesions and L-Mets (r = 0.250, p = 0.071). The CD133-positive rate in primary lesions and L-Mets was 53.6 and 44.6 %, respectively. There was no correlation of CD133 expression between primary lesions and L-Mets (r = 0.219, p = 0.135). In the CD133-negative group, the MIB-1 index was significantly higher than in the CD133-positive group (61.6 vs. 46.3 %, p = 0.003), and E-cadherin expression was significantly lower in the CD133-negative group compared with the CD133-positive group (29.3 vs. 46.8 %, p = 0.001). Absence of CD133 expression in L-Mets correlated with poor overall survival (p = 0.006), and multivariate regression analysis showed that it was an independent marker for poor survival (hazard ratio 0.320, p = 0.0016).

Research Products

• [Journal Article] ALPPS: Short-term Outcome and Functional Changes in the Future Liver Remnant. (2015)
  • Author(s): Tanaka K, Endo I.
  • Journal Title: Ann Surg. Volume: 262 Issue: 2 Pages: e88-e89
  • DOI: 10.1097/sla.0000000000000665
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Low infiltration of peritumoral regulatory T cells predicts worse outcome following resection of colorectal liver metastases. (2015)
  • Author(s): Nakagawa K, Tanaka K, Homma Y, Nojiri K, Kumamoto T, Takeda K, Endo I.
  • Journal Title: Low infiltration of peritumoral regulatory T cells predicts worse outcome following resection of colorectal liver metastases. Volume: 22 Issue: 1 Pages: 180-186
  • DOI: 10.1245/s10434-014-3974-1
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Adjuvant treatment with tumor-targeting Salmonella typhimurium A1-R reduces recurrence and increases survival after liver metastasis resection in an orthotopic nude mouse model. (2015)
  • Author(s): Murakami T, Hiroshima Y, Zhao M, Zhang Y, Chishima T, Tanaka K, Bouvet M, Endo I, Hoffman RM.
  • Journal Title: Oncotarget Volume: 6 Issue: 39 Pages: 41856-41862
  • DOI: 10.18632/oncotarget.6170
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Fluorescence-Guided Surgery of Liver Metastasis in Orthotopic Nude-Mouse Models. (2015)
  • Author(s): Murakami T, Hiroshima Y, Zhang Y, Chishima T, Tanaka K, Bouvet M, Endo I, Hoffman RM.
  • Journal Title: PLoS One Volume: 10 Issue: 10 Pages: e0138752-e0138752
  • DOI: 10.1371/journal.pone.0138752
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Therapeutic efficacy of tumor-targeting Salmonella typhimurium A1-R on human colorectal cancer liver metastasis in orthotopic nude-mouse models. (2015)
  • Author(s): Murakami T, Hiroshima Y, Zhao M, Zhang Y, Chishima T, Tanaka K, Bouvet M, Endo I, Hoffman RM.
  • Journal Title: Oncotarget Volume: 6 Issue: 31 Pages: 31368-31377
  • DOI: 10.18632/oncotarget.5187
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Tumor-Targeting Salmonella typhimurium A1-R Arrests a Chemo-Resistant Patient Soft-Tissue Sarcoma in Nude Mice. (2015)
  • Author(s): Hiroshima Y, Zhao M, Zhang Y, Zhang N, Maawy A, Murakami T, Mii S, Uehara F, Yamamoto M, Miwa S, Yano S, Momiyama M, Mori R, Matsuyama R, Chishima T, Tanaka K, Ichikawa Y, Bouvet M, Endo I, Hoffman RM.
  • Journal Title: PLoS One Volume: 10 Issue: 8 Pages: e0134324-e0134324
  • DOI: 10.1371/journal.pone.0134324
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Efficacy of tumor-targeting Salmonella typhimurium A1-R in combination with anti-angiogenesis therapy on a pancreatic cancer patient-derived orthotopic xenograft (PDOX) and cell line mouse models. (2014)
  • Author(s): Hiroshima Y, Zhang Y, Murakami T, Maawy A, Miwa S, Yamamoto M, Yano S, Sato S, Momiyama M, Mori R, Matsuyama R, Chishima T, Tanaka K, Ichikawa Y, Bouvet M, Endo I, Zhao M, Hoffman RM.
  • Journal Title: Oncotarget Volume: 15;5(23) Pages: 12346-57
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Efficacy of Salmonella typhimurium A1-R Versus Chemotherapy on a Pancreatic Cancer Patient-Derived Orthotopic Xenograft (PDOX). (2014)
  • Author(s): Hiroshima Y, Zhao M, Maawy A, Zhang Y, Katz MH, Fleming JB, Uehara F, Miwa S, Yano S, Momiyama M, Suetsugu A, Chishima T, Tanaka K, Bouvet M, Endo I, Hoffman RM.
  • Journal Title: J Cell Biochem Volume: 115(7) Issue: 7 Pages: 1254-61
  • DOI: 10.1002/jcb.24769
  • Peer Reviewed
• [Journal Article] Successful fluorescence-guided surgery on human colon cancer patient-derived orthotopic xenograft mouse models using a fluorophore-conjugated anti-CEA antibody and a portable imaging system. (2014)
  • Author(s): Hiroshima Y, Maawy A, Metildi CA, Zhang Y, Uehara F, Miwa S, Yano S, Sato S, Murakami T, Momiyama M, Chishima T, Tanaka K, Bouvet M, Endo I, Hoffman RM.
  • Journal Title: J Laparoendosc Adv Surg Tech A. Volume: 24(4) Issue: 4 Pages: 241-7
  • DOI: 10.1089/lap.2013.0418
  • Peer Reviewed
• [Journal Article] The tumor-educated-macrophage increase of malignancy of human pancreatic cancer is prevented by zoledronic acid. (2014)
  • Author(s): Hiroshima Y, Maawy A, Hassanein MK, Menen R, Momiyama M, Murakami T, Miwa S, Yamamoto M, Uehara F, Yano S, Mori R, Matsuyama R, Chishima T, Tanaka K, Ichikawa Y, Bouvet M, Endo I, Hoffman RM.
  • Journal Title: PLoS One. Volume: 12;9(8) Issue: 8 Pages: e103382-e103382
  • DOI: 10.1371/journal.pone.0103382
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Fluorescence-guided surgery in combination with UVC irradiation cures metastatic human pancreatic cancer in orthotopic mouse models. (2014)
  • Author(s): Hiroshima Y, Maawy A, Zhang Y, Sato S, Murakami T, Yamamoto M, Uehara F, Miwa S, Yano S, Momiyama M, Chishima T, Tanaka K, Bouvet M, Endo I, Hoffman RM.
  • Journal Title: PLoS One. Volume: 12;9(6) Issue: 6 Pages: e99977-e99977
  • DOI: 10.1371/journal.pone.0099977
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Patients with CD133-negative colorectal liver metastasis have a poor prognosis after hepatectomy (2014)
  • Author(s): Yamamoto S, Nagashima Y et al
  • Journal Title: Ann Surg Oncol Volume: 21(6) Issue: 6 Pages: 1853-61
  • DOI: 10.1245/s10434-014-3549-1
  • Peer Reviewed
• [Presentation] The correlation between the change of future liver remnant volume and functional capacity in ALPPS (associating liver partition and portal vein ligation for staged hepatectomy), and establishment of ALPPS model in rats (2015)
  • Author(s): Kawaguchi Daisuke, Yukihiko Hiroshima, Takashi Murakami, Kenichi Matsuo, Chihiro Kosugi, Kiyohiko Syuto, Masashi Momiyama, Itaru Endo, Keiji Koda, Kuniya Tanaka
  • Organizer: AACR
  • Place of Presentation: Philadelphia, USA
  • Year and Date: 2015-04-20
  • Int'l Joint Research
• [Presentation] Curative fluorescence-guided surgery of pancreatic cancer in combination with UVC irradiation in orthotopic mouse models (2015)
  • Author(s): Yukihiko Hiroshima, Ali Maawy, Yong Zhang, Sho Sato, Takashi Murakami, Mako Yamamoto, Fuminari Uehara, Shinji Miwa, Shuya Yano, Masashi Momiyama, Takashi Chishima, Kuniya Tanaka, Michael Bouvet, Itaru Endo, Robert M. Hoffman
  • Organizer: AACR
  • Place of Presentation: Philadelphia, USA
  • Year and Date: 2015-04-20
  • Int'l Joint Research
• [Presentation] Fluorescence-guided surgery with an anti-CA 19-9-conjugated fluorophore in combination with neoadjuvant chemotherapy inhibits metastatic recurrence in a pancreatic cancer patient derived orthotopic xenograft (PDOX) nude mouse model (2015)
  • Author(s): Yukihiko Hiroshima1, Ali Maawy2, Yong Zhang3, Takashi Murakami4, Masashi Momiyama4, Ryutaro Mori4, Ryusei Matsuyama4, Matthew H. Katz5, Jason B. Fleming5, Takashi Chishima4, Kuniya Tanaka4, Yasushi ichikawa4, Itaru Endo4, Robert M. Hoffman6, Michael Bouvet2.
  • Organizer: 米国癌学会（AACR annual meeting 2015）
  • Place of Presentation: Philadelphia、米国
  • Year and Date: 2015-04-19 – 2015-04-22
• [Presentation] Efficacy of photo-immunotherapy in combination with surgical resection on a pancreatic cancer patient derived orthotopic xenograft (PDOX) (2015)
  • Author(s): Yukihiko Hiroshima1, Ali Maawy2, Takashi Murakami1, Nzola De Magalhães2, Daisuke Kawaguchi3, Kenichi Matsuo3, Kuniya Tanaka3, Michael Bouvet2, Robert M. Hoffman2, Itaru Endo1.
  • Organizer: 米国癌学会（AACR annual meeting 2015）
  • Place of Presentation: Philadelphia、米国
  • Year and Date: 2015-04-19 – 2015-04-22
• [Presentation] The correlation between the change of future remnant liver volume and functional capacity in ALPPS (associating liver partition and portal vein ligation for staged hepatectomy), and establishment of ALPPS model in rats (2015)
  • Author(s): Daisuke Kawaguchi1, Yukihiko Hiroshima1, Takashi Murakami1, Kenichi Matsuo1, Chihiro Kosugi1, Kiyohiko Syuto1, Akimitsu Yamada2, Itaru Endo2, Keiji Koda1, Kuniya Tanaka1.
  • Organizer: 米国癌学会（AACR annual meeting 2015）
  • Place of Presentation: Philadelphia、米国
  • Year and Date: 2015-04-19 – 2015-04-22
• [Presentation] Fluorescence-guided surgery of liver metastasis in orthotopic nude-mouse models (2015)
  • Author(s): Takashi Murakami1, Yukihiko Hiroshima1, Shinji Miwa1, Yano Shuya1, Makoto Toneri1, Mako Yamamoto1, Masashi Momiyama2, Takashi Chishima2, Kuniya Tanaka2, Michael Bouvet1, Satoshi Hasegawa2, Itaru Endo2, Robert M. Hoffman3.
  • Organizer: 米国癌学会（AACR annual meeting 2015）
  • Place of Presentation: Philadelphia、米国
  • Year and Date: 2015-04-19 – 2015-04-22
• [Presentation] Curative fluorescence-guided surgery of pancreatic cancer in combination with UVC irradiation in orthotopic mouse models (2015)
  • Author(s): Yukihiko Hiroshima1, Ali Maawy2, Yong Zhang1, Sho Sato3, Takashi Murakami1, Mako Yamamoto1, Fuminari Uehara1, Shinji Miwa1, Shuya Yano1, Masashi Momiyama3, Takashi Chishima3, Kuniya Tanaka3, Michael Bouvet2, Itaru Endo3, Robert M. Hoffman2.
  • Organizer: 米国癌学会（AACR annual meeting 2015）
  • Place of Presentation: Philadelphia、米国
  • Year and Date: 2015-04-19 – 2015-04-22
• [Presentation] 大腸癌肝転移巣における癌幹細胞マーカー (CD44,CD133)発現の意義 (2013)
  • Author(s): 山本晋也
  • Organizer: 日本外科学会学術集会
  • Place of Presentation: 福岡国際会議場(福岡県)
• [Presentation] 大腸癌肝転移巣におけるCD133発現の意義
  • Author(s): 山本晋也
  • Organizer: 第33回癌免疫外科研究会
  • Place of Presentation: 新横浜プリンスホテル(神奈川県)