Study of the correlation between disseminated cancer cells and host factors in establishment of recurrence and metastasis of hepatocellular carcinoma

• Project/Area Number: 21390369
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: Hokkaido University
• Principal Investigator: KAMIYAMA Toshiya 北海道大学, 大学院・医学研究科, 准教授 (80322816)
• Co-Investigator(Kenkyū-buntansha): NAKANISHI Kazuaki 北海道大学, 大学院・医学研究科, 特任助教 (80374338) ; YOKOO Hideki 北海道大学, 北海道大学病院, 医員 (70399947) ; TAHARA Munenori 北海道大学, 北海道大学病院, 医員 (30306576) ; TODO Satoru 北海道大学, 大学院・医学研究科, 特任教授 (60136463)
• Project Period (FY): 2009 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥17,810,000 (Direct Cost: ¥13,700,000、Indirect Cost: ¥4,110,000); Fiscal Year 2011: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2010: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2009: ¥12,480,000 (Direct Cost: ¥9,600,000、Indirect Cost: ¥2,880,000)
• Keywords: 遊離癌細胞 / 癌幹細胞 / CD133 / 肝細胞癌 / 大腸癌 / AFPmRNA / VEGFR1mRNA

Research Abstract

Cytoplasmic expression of CD133 in HCC is associated with elevated serum AFP level, histologically high-grade tumor, and tumor invasion to the major branch of the portal vein. Positive cytoplasmic expression of CD133 represented the risk of poor prognosis. CD133 overexpression was an independent prognostic factor for PS of colorectal cancer (CRC) patients. Evaluation of the frequency and pattern of CD133 expression is useful for predicting prognosis, recurrence, and chemosensitivity in CRC patients. We found a significant tendency for patients who were positive for BM-AFP mRNA to experience recurrence within 1 year after surgery compared to those negative for BM-AFP mRNA. The BM-VEGFR-1 mRNA level of all HCC patients was higher than that of normal controls and the PH-VEGFR-1 mRNA level of almost all patients was higher that of normal controls. The classification by BM-VEGFR-1 mRNA/BM-AFP mRNA was a significant risk factor for recurrence within 1 year after surgery. The importance of the coexistence of disseminated cancer cells and VEGFR-1-positive hematopoietic bone marrow progenitor cells was also proved because the DFS curve of patients negative for BM-AFP mRNA and BM-VEGFR-1 mRNA ; low was better in the other 3 groups. The evaluation of BM-AFP and BM-VEGFR-1 mRNA in patients with HCC may be a valuable predictor of disease recurrence following curative resection.

Research Products

• [Journal Article] alpha-Fetoprotein, vascular endothelial growth factor receptor-1 and early recurrence of hepatoma (2012)
  • Author(s): Toshiya Kamiyama, Masato Takahashi, Kazuaki Nakanishi, Hideki Yokoo, Hirofumi Kamachi, Nozomi Kobayashi, Michitaka Ozaki, Satoru Todo
  • Journal Title: World Journal of Gastrenterology Volume: 18(4) Issue: 4 Pages: 340-348
  • DOI: 10.3748/wjg.v18.i4.340
  • Peer Reviewed
• [Journal Article] Effectiveness of Using Ultrasonically Activated Scalpel in Combination with Radiofrequency Dissecting Sealer or Irrigation Bipolar for Hepatic Resection (2012)
  • Author(s): Hideki Yokoo, Toshiya Kamiyama, Kazuaki Nakanishi, Munenori Tahara : Daisuke Fukumori, Hirofumi Kamachi, Michiaki Matsushita, Satoru Todo
  • Journal Title: Hepatogastroenterology Volume: 59(115) Pages: 831-5
  • Peer Reviewed
• [Journal Article] Relationship between Diffusion-Weighted Magnetic Resonance Imaging and Histological Tumor Grading of Hepatocellular Carcinoma (2012)
  • Author(s): Nakanishi M, Chuma M, Hige S, Omatsu T, Yokoo H, Nakanishi K, Kamiyama T, Kubota K, Haga H, Matsuno Y, Onodera Y, Kato M, Asaka M.
  • Journal Title: Ann Surg Oncol Volume: 19 Issue: 4 Pages: 1302-1309
  • DOI: 10.1245/s10434-011-2066-8
  • Peer Reviewed
• [Journal Article] rm outcome of laparoscopic hepatectomy in patients with hepatocellular ca (2012)
  • Author(s): Kamiyama T
  • Journal Title: Hepato-Gastroenterology Volume: (印刷中)
  • Peer Reviewed
• [Journal Article] Analysis of the risk factors for hyperbilirubinemia after hepatectomy (2011)
  • Author(s): Daisuke Fukumori, Toshiya Kamiyama, Kazuaki Nakanishi, Hideki okoo, Munenori Tahara, Hirofumi Kamachi, Michiaki Matsushita, Satoru Todo
  • Journal Title: Hepatobiliary Pancreat Sci Volume: 18(5) Issue: 5 Pages: 724-30
  • DOI: 10.1007/s00534-011-0394-5
  • Peer Reviewed
• [Journal Article] Co-expression of Mesothelin and CA125 Correlates with Unfavorable Patient Outcome in Pancreatic Ductal Adenocarcinoma (2011)
  • Author(s): Einama T, Kamachi H, Nishihara H, Homma S, Kanno H, Takahashi K, Sasaki A, Tahara M, Okada K, Muraoka S, Kamiyama T, matsuno Y, Ozaki M, Todo S
  • Journal Title: Pancreas Volume: 40(8) Issue: 8 Pages: 1276-82
  • DOI: 10.1097/mpa.0b013e318221bed8
  • Peer Reviewed
• [Journal Article] Clinicopathological significance of nuclear factor -□B activation in hepatocellular carcinoma. Constitutive activation of NF-□B in advanced HCC (2011)
  • Author(s): Hideki Yokoo, Jun Yasuda, Kazuaki Nakanishi1, Makoto Chuma, Toshiya Kamiyama, Satoru Todo, Setsuo Hirohashi, and Michiie Sakamoto
  • Journal Title: HepatologyResearch Volume: 41(3) Issue: 3 Pages: 240-249
  • DOI: 10.1111/j.1872-034x.2010.00758.x
  • Peer Reviewed
• [Journal Article] Liver transplantation for hepatocellular carcinoma : the Japanese experience. (2010)
  • Author(s): Furukawa H, Shimamura T, Suzuki T, Taniguchi M, Nakanishi K, Yamashita K, Kamiyama T, Matsushita M, Todo S
  • Journal Title: J Hepatobiliary Pancreat Sci Volume: 17(5) Issue: 5 Pages: 533-8
  • DOI: 10.1007/s00534-009-0168-5
  • NAID: 10027662898
  • Peer Reviewed
• [Journal Article] The impact of anatomical resection for hepatocellular carcinoma that meets the milan criteria (2010)
  • Author(s): Kamiyama T, Nakanishi K, Yokoo H, Kamachi H, Matsushita M, Todo S
  • Journal Title: J Surg Oncol Volume: 101(1) Issue: 1 Pages: 54-60
  • DOI: 10.1002/jso.21414
  • Peer Reviewed
• [Journal Article] Cytoplasmic expression of CD133 is an important risk factor for overall survival in hepatocellular carcinoma (2010)
  • Author(s): Sasaki A, Kamiyama T, Yokoo H, Nakanishi K, Kubota K, Haga H, Matsushita M, Ozaki M, Matsuno Y, Todo S.
  • Journal Title: Oncol Rep Volume: 24(2) Issue: 2 Pages: 537-46
  • DOI: 10.3892/or_00000890
  • NAID: 120003207584
  • Peer Reviewed
• [Journal Article] Perioperative Management of Hepatic Resection Toward Zero Mortality and Morbidity : Analysis of 793 Consecutive Cases in a Single Institution. (2010)
  • Author(s): Kamiyama T, Nakanishi K, Yokoo H, Kamachi H, Tahara M, Yamashita K, Taniguchi M, Shimamura T, Matsushita M, Todo S
  • Journal Title: J Am Coll Surg Volume: 211(4) Issue: 4 Pages: 443-9
  • DOI: 10.1016/j.jamcollsurg.2010.06.005
  • Peer Reviewed
• [Journal Article] Frequency and pattern of expression of the stem cell marker CD133 have strong prognostic effect on the surgical outcome of colorectal cancer patients (2010)
  • Author(s): Takahashi S, Kamiyama T, Tomaru U, Ishizu A, Shida T, Osaka M, Sato Y, Saji Y, Ozaki M, Todo S
  • Journal Title: Oncol Rep Volume: 24(5) Issue: 5 Pages: 1201-12
  • DOI: 10.3892/or_00000973
  • Peer Reviewed
• [Journal Article] Cytoplasmic expression of CD133 is an important risk factor for overall survival in hepatocellular carcinoma (2010)
  • Author(s): Sasaki A, Kamiyama T, et al
  • Journal Title: Oncol Rep. Volume: 24 Pages: 537-546
  • NAID: 120003207584
  • Peer Reviewed
• [Journal Article] Frequency and pattern of expression of the stem cell marker CD133 have strong prognostic effect on the surgical outcome of colorectal cancer (2010)
  • Author(s): Takahashi S, Kamiyama T, et al
  • Journal Title: Oncol Rep. Volume: 24 Pages: 1201-12
  • Peer Reviewed
• [Journal Article] The impact of anatomical resection for hepatocellular carcinoma that meets the milan criteria. (2010)
  • Author(s): T.Kamiyama
  • Journal Title: J Surg Oncol. 101 Pages: 54-60
  • Peer Reviewed
• [Journal Article] Recurrence patterns after hepatectomy of hepatocellular carcinoma : implication of milan criteria utilization. (2009)
  • Author(s): Kamiyam T, Nakanishi K, Yokoo H, Kamachi H, Tahara M, Suzuki T, Shimamura T, Furukawa H, Matsushita M, Todo S
  • Journal Title: Ann Surg Oncol Volume: 16(6) Issue: 6 Pages: 1560-71
  • DOI: 10.1245/s10434-009-0407-7
  • Peer Reviewed
• [Journal Article] The influence of hepatitis B DNA level and antiviral therapy on recurrence after initial curative treatment in patients with hepatocellular carcinoma (2009)
  • Author(s): Chuma M, Hige S, Kamiyama T, Meguro T, Nagasaka A, Nakanishi K, Yamamoto Y, Nakanishi M, Kohara T, Sho T, Yamamoto K, Horimoto H, Kobayashi T, Yokoo H, Matsushita M, Todo S, Asaka M
  • Journal Title: J Gastroenterol Volume: 44(9) Issue: 9 Pages: 991-9
  • DOI: 10.1007/s00535-009-0093-z
  • NAID: 10025581551
  • Peer Reviewed
• [Journal Article] Recurrence patterns after hepatectomy of hepatocellular carcinoma : implication of milan criteria utilization. (2009)
  • Author(s): T.Kamiyama
  • Journal Title: Ann Surg Oncol. 16 Pages: 1560-71
  • Peer Reviewed
• [Journal Article] Long-term outcome of laparoscopic hepatectomy in patients with hepatocellular carcinoma
  • Author(s): Toshiya Kamiyama , Munenori Tahara, Kazuaki Nakanishi, Hideki Yokoo, Hirofumi Kamachi, Tatsuhiko Kakisaka, Yosuke Tsuruga, Michiaki Matsushita, Satoru Todo
  • Journal Title: Hepato-Gastroenterology Volume: (in press)
  • Peer Reviewed
• [Presentation] ION WITHIN 1 YEAR AFTER HEPATECTOMY FOR THE PATIENTS WITH HEPATOCELLULAR (2012)
  • Author(s): Kmiyama T
  • Organizer: American Hepato-Pancreato-Biliary Association Annual Meeting
  • Place of Presentation: Eden Roc Renaissance Resort (USA)
  • Year and Date: 2012-03-12
• [Presentation] 再発肝細胞癌への治療戦略Salvage肝移植を考慮して (2011)
  • Author(s): 神山俊哉、中西一彰、横尾英樹、蒲池浩文、田原宗徳、柿坂達彦、小丹枝裕二、山下健一郎、谷口雅彦、鈴木知己、嶋村剛、古川博之、松下通明、藤堂省
  • Organizer: 第111回日本外科学会定期学術集会
  • Place of Presentation: 東京国際フォーラム
• [Presentation] ANALYZE OF THE RISK FACTORS OF DEATH FROM CANCER PROGRESSION WITHIN 1 YEAR AFTER HEPATECTOMY FOR THE PATIENTS WITH HEPATOCELLULAR CARCINOMA (HCC) (2011)
  • Author(s): T. Kamiyama
  • Organizer: Annual meeting American Hepato-Pancreato-Biliary Association Miami Beach
  • Place of Presentation: Eden Roc
• [Presentation] AFPmRNA and VEGFR1mRNA detacted in bone marrow by real time PCR relate early recurrence after curative hepatectomy for hapetocellular carcinoma (2011)
  • Author(s): Kamiyama T
  • Organizer: The International Liver Cancer Association Fourth Annual Conference
  • Place of Presentation: Montreal, Canada
• [Presentation] 発現頻度・発現パターンから見た大腸癌における癌幹細胞マーカーCD133の臨床的意義についての検討 (2010)
  • Author(s): 高橋周作,神山俊哉,島田信吾,工藤岳秋,廣瀬邦弘,佐治裕,崎浜秀康,尾崎倫孝,外丸詩野,石津明洋,藤堂省
  • Organizer: 日本外科学会
  • Place of Presentation: 名古屋国際会議場
• [Presentation] 肝細胞癌におけるCD133発現の臨床病理学的意義 (2010)
  • Author(s): 佐々木彩実,神山俊哉,横尾英樹,中西一彰,久保田佳奈子,羽賀博典,松下通明,尾崎倫孝,松野吉宏,藤堂省
  • Organizer: 日本外科学会
  • Place of Presentation: 名古屋国際会議場
• [Presentation] Cytoplasmic expression of CD133 is an important risk factor for overall survival in hepatocellular carcinoma. (2010)
  • Author(s): Sasaki A, Kamiyama T
  • Organizer: The International Liver Cancer Association Fourth Annual Conference
  • Place of Presentation: Montreal, Canada
• [Presentation] 肝細胞癌切除後再発への治療戦略-salvage肝移植を考慮して- (2010)
  • Author(s): 神山俊哉、中西一彰、横尾英樹、蒲池浩文、田原宗徳、福森大介、山下健一郎、谷口雅彦、鈴木知己、嶋村剛、古川博之、松下通明、藤堂省
  • Organizer: 第65回日本消化器外科学会総会
  • Place of Presentation: 海峡メッセ下関
• [Presentation] 1年以内に癌死する肝細胞癌症例の検討 (2010)
  • Author(s): 神山俊哉、中西一彰、横尾英樹、蒲池浩文、谷口雅彦、田原宗徳、柿坂達彦、松下通明、藤堂省
  • Organizer: 第72回日本臨床外科学会総会
  • Place of Presentation: パシフィコ横浜
• [Presentation] AFPMRNA AND VEGFR-1IMRNA DETECTED IN BONE MARROW BY REAL-TIME QUANTITATIVE RT-PCR RELATE EARLY RECURRENCE AFTER CURATIVE HEPATECTOMY (2010)
  • Author(s): Kamiyama T
  • Organizer: International Liver Cancer Association Fourth Annual Conference
  • Place of Presentation: Montreal, Canada
• [Presentation] The efficacy of anatomical resection forhepatocellular carcinoma within the Milan criteria (2009)
  • Author(s): Toshiya Kamiyama
  • Organizer: 2009 Annual meeting American Hepato-Pancreato-Biliary Association Miami Beach
  • Place of Presentation: Eden Roc
• [Presentation] 大腸癌症例におけるCD133の発現と臨床的意義 (2009)
  • Author(s): 高橋周作,神山俊哉,外丸詩野,工藤岳明,旭火華,広瀬邦弘,佐治裕,崎浜秀康,片岡昭彦,藤堂省
  • Organizer: 日本消化器外科学会
  • Place of Presentation: リーガロイヤルホテル大阪
• [Presentation] 大腸癌切除症例におけるCD133陽性細胞の臨床病理学的意義 (2009)
  • Author(s): 高橋周作
  • Organizer: 第64回日本消化器外科学会定期学術総会
  • Place of Presentation: 大阪国際会議場(大阪)