New cancer treatment focusing on genetic instability of the cancer stem cell

2013 Fiscal Year Final Research Report

• Project/Area Number: 24659614
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Single-year Grants
• Research Field: Digestive surgery
• Research Institution: Kyushu University
• Principal Investigator: MAEHARA Yoshihiko 九州大学, 医学(系)研究科(研究院), 教授 (80165662)
• Project Period (FY): 2012-04-01 – 2014-03-31
• Keywords: 染色体不安定性 / 酸化ストレス / BuBR1 / p53 / がん幹細胞 / LgR5

Research Abstract

The cancer stem cell remains to be resistant to the treatment such as chemotherapy or the radiation. We can propose a new treatment to reduce recurrence and metastasis by targetting the cancer stem cell. Because a cancer is exposed to hypoxia and chemical irritation partially, some cells become a stem like cell and become to generate genetic instability.
In our experiment,oxidative stress (OS) causes DNA damage and chromosome instability that may lead to carcinogenesis. OS is also suggested to contribute to an increase in aneuploid cells. However, it is not clear how OS is involved in the regulation of SAC and contributes to carcinogenesis associated with aneuploidy. Here we show that an oxidant (KBrO3) activated the p53 signaling pathway and suppressed the expression of SAC factors, BubR1, and Mad2, in human diploid fibroblast MRC5 cells. This suppression was dependent on functional p53 and reactive oxygen species.

Research Products

• [Journal Article] Prognostic impact of programmed cell death 1 ligand 1 expression in human leukocyte antigen class I-positive hepatocellular carcinoma after curative hepatectomy (2014)
  • Author(s): Umemoto Y, Okano S, Matsumoto Y, Nakagawara H, Matono R, Yoshiya S, Yamashita YI, Yoshizumi T, Ikegami T, Soejima Y, Harada M, Aishima S, Oda Y, Shirabe K, Maehara Y
  • Journal Title: J Gastroenterol
• [Journal Article] A novel serum marker, glycosylated Wisteria floribunda agglutinin-positive Mac-2 binding protein (WFA-M2BP), for assessing liver fibrosis (2014)
  • Author(s): Toshima T, Shirabe K, Ikegami T, Yoshizumi T, Kuno A, Togayachi A, Gotoh M, Narimatsu H, Korenaga M, Mizokami M, Nishie A, Aishima S, Maehara Y
  • Journal Title: J Gastroenterol
• [Journal Article] Allelic Imbalance at an 8q24 Oncogenic SNP is Involved in Activating MYC in Human Colorectal Cancer (2014)
  • Author(s): Sugimachi K, Niida A, Yamamoto K, Shimamura T, Imoto S, Iinuma H, Shinden Y, Eguchi H, Sudo T, Watanabe M, Tanaka J, Kudo S, Hase K, Kusunoki M, Yamada K, Shimada Y, Sugihara K, Maehara Y, Miyano S, Mori M, Mimori K
  • Journal Title: Ann Surg Oncol
• [Journal Article] Phase II Study of Docetaxel and S-1 (DS) as Neoadjuvant Chemotherapy for Clinical Stage III Resectable Gastric Cancer (2014)
  • Author(s): Oki E, Emi Y, Kusumoto T, Sakaguchi Y, Yamamoto M, Sadanaga N, Shimokawa M, Yamanaka T, Saeki H, Morita M, Takahashi I, Hirabayashi N, Sakai K, Orita H, Aishima S, Kakeji Y, Yamaguchi K, Yoshida K, Baba H, Maehara Y
  • Journal Title: Ann Surg Oncol
• [Journal Article] Rad51 expression is a useful predictive factor for the efficacy of neoadjuvant chemoradiotherapy in squamous cell carcinoma of the esophagus (2014)
  • Author(s): Nakanoko T, Saeki H, Morita M, Nakashima Y, Ando K, Oki E, Ohga T, Kakeji Y, Toh Y, Maehara Y
  • Journal Title: Ann Surg Oncol Volume: 21 Pages: 597-604
• [Journal Article] Balloon-occluded retrograde transvenous obliteration is feasible for prolonged portosystemic shunts after living donor liver transplantation (2014)
  • Author(s): Nagao Y, Akahoshi T, Uehara H, Hashimoto N, Kinjo N, Kawanaka H, Tomikawa M, Uchiyama H, Yoshizumi T, Soejima Y, Shirabe K, Maehara Y
  • Journal Title: Surg Today Volume: 44 Pages: 633-639
• [Journal Article] Technical improvement of total pharyngo-laryngo-esophagectomy for esophageal cancer and head and neck cancer (2014)
  • Author(s): Morita M, Saeki H, Ito S, Ikeda K, Yamashita N, Ando K, Hiyoshi Y, Ida S, Tokunaga E, Uchiyama H, Oki E, Ikeda T, Yoshida S, Nakashima T, Maehara Y
  • Journal Title: Ann Surg Oncol Volume: 21 Pages: 1671-1677
• [Journal Article] Gender differences in prognosis after esophagectomy for esophageal cancer (2014)
  • Author(s): Morita M, Otsu H, Kawano H, Kasagi Y, Kimura Y, Saeki H, Ando K, Ida S, Oki E, Tokunaga E, Ikeda T, Kusumoto T, Maehara Y
  • Journal Title: Surg Today Volume: 44 Pages: 505-512
• [Journal Article] Prognostic and Therapeutic Implications of Aromatase Expression in Lung Adenocarcinomas with EGFR mutations (2014)
  • Author(s): Kohno M, Okamoto T, Suda K, Shimokawa M, Kitahara H, Shimamatsu S, Konishi H, Yoshida T, Takenoyama M, Yano T, Maehara Y
  • Journal Title: Clin Cancer Res
• [Journal Article] Significance of preoperative evaluation of the right gastroepiploic artery graft to the coronary artery in patients undergoing abdominal surgery (2014)
  • Author(s): Ito S, Yamaguchi S, Saeki H, Oki E, Tayama E, Ikejiri K, Morita M, Maehara Y
  • Journal Title: World JSurg Volume: 38 Pages: 1051-1057
• [Journal Article] Splenic volume may be a useful indicator of the protective effect of bevacizumab against oxaliplatin-induced hepatic sinusoidal ostruction syndrome (2014)
  • Author(s): Imai K, Emi Y, Iyama KI, Beppu T, Ogata Y, Kakeji Y, Samura H, Oki E, Akagi Y, Maehara Y, Baba H
  • Journal Title: Ear JSurg Oncol Volume: 40 Pages: 559-566
• [Journal Article] A high MELD score, combined with the presence of hepatitis C, is associated with a poor prognosis in living donor liver transplantation (2014)
  • Author(s): Ikegami T, Shirabe K, Yoshiya S, Yoshizumi T, Yamashita Y, Harimoto N, Toshima T, Uchiyama H, Soejima Y, Maehara Y
  • Journal Title: Surg Today Volume: 44 Pages: 233-240
• [Journal Article] Surgical resection of hypopharynx and cervical esophageal cancer with a history of esophagectomy for thoracic esophageal cancer (2014)
  • Author(s): Ida S, Morita M, Hiyoshi Y, Ikeda K, Ando K, Kimura Y, Saeki H, Oki E, Kusumoto T, Yoshida S, Nakashima T, Watanabe M, Baba H, Maehara Y
  • Journal Title: Ann Surg Oncol Volume: 21 Pages: 1175-1181
• [Journal Article] Contribution of Aurora-A and -B expression to DNA aneuploidy in gastric cancers (2014)
  • Author(s): Honma K, Nakanishi R, Nakanoko T, Ando K, Saeki H, Oki E, Iimori M, Kitao H, Kakeji Y, Maehara Y
  • Journal Title: Surg Today Volume: 44 Pages: 454-461
• [Journal Article] Impact of GATA-3 and FOXA1 expression in patients with hormone receptor-positive/HER2-negative breast cancer (2014)
  • Author(s): Hisamatsu Y, Tokunaga E, Yamashita N, Akiyoshi S, Okada S, Nakashima Y, Taketani K, Aishima S, Oda Y, Morita M, Maehara Y
  • Journal Title: Breast Cancer
• [Journal Article] Mortalin is a prognostic factor of gastric cancer with normal p53 function (2014)
  • Author(s): Ando K, Oki E, Zhao Y, Ikawa-Yoshida A, Kitao H, Saeki H, Kimura Y, Ida S, Morita M, Kusumoto T, Maehara Y
  • Journal Title: Gastric Cancer Volume: 17 Pages: 255-262
• [Journal Article] Rendezvous ductoplasty for biliary anastomotic stricture after living-donor liver transplantation (2013)
  • Author(s): Yoshiya S, Shirabe K, Matsumoto Y, Ikeda T, Soejima Y, Yoshizumi T, Uchiyama H, Ikegami T, Harimoto N, Maehara Y
  • Journal Title: Transplantation Volume: 95 Pages: 1278-1283
• [Journal Article] DVC1-0101 to treat peripheral arterial disease : a Phase I/IIa open-label dose-escalation clinical trial (2013)
  • Author(s): Yonemitsu Y, Matsumoto T, Itoh H, Okazaki J, Uchiyama M, Yoshida K, Onimaru M, Onohara T, Inoguchi H, Kyuragi R, Shimokawa M, Ban H, Tanaka M, Inoue M, Shu T, Hasegawa M, Nakanishi Y, Maehara Y
  • Journal Title: Mol Ther Volume: 21 Pages: 707-714
• [Journal Article] Surgical outcomes of pancreaticoduodenectomy for periampullary tumors in elderly patients (2013)
  • Author(s): Yamashita Y, Shirabe K, Tsujita E, Takeishi K, Ikeda T, Yoshizumi T, Furukawa Y, Ishida T, Maehara Y
  • Journal Title: Langenbecks Arch Surg Volume: 398 Pages: 539-545
• [Journal Article] Third or more repeat hepatectomy for recurrent hepatocellular carcinoma (2013)
  • Author(s): Yamashita Y, Shirabe K, Tsuijita E, Takeishi K, Ikegami T, Yoshizumi T, Soejima Y, Ikeda T, Utsunomiya T, Maehara Y
  • Journal Title: Surgery Volume: 154 Pages: 1038-1045
• [Journal Article] Risk factors for recurrence after curative resection of hepatitis C-related hepatocellular carcinoma in patients without postoperative interferon therapy (2013)
  • Author(s): Yamashita Y, Shirabe K, Toshima T, Tsuijita E, Takeishi K, Harimoto N, Ikegami T, Yoshizumi T, Ikeda T, Soejima Y, Maehara Y
  • Journal Title: Hepatol Res Volume: 43 Pages: 1313-1320
• [Journal Article] Vimentin as a poor prognostic factor for triple-negative breast cancer (2013)
  • Author(s): Yamashita N, Tokunaga E, Kitao H, Hisamatsu Y, Taketani K, Akiyoshi S, Okada S, Aishima S, Morita M, Maehara Y
  • Journal Title: J Cancer Res Clin Oncol Volume: 139 Pages: 739-746
• [Journal Article] Rad9, Rad17, TopBP1 and claspin play essential roles in heat-induced activation of ATR kinase and heat tolerance (2013)
  • Author(s): Tuul M, Kitao H, Iimori M, Matsuoka K, Kiyonari S, Saeki H, Oki E, Morita M, Maehara Y
  • Journal Title: PLoS One Volume: 8 Pages: e55361
• [Journal Article] Image-guided laparoscopic surgery in an open MRI operating theater (2013)
  • Author(s): Tsutsumi N, Tomikawa M, Uemura M, Akahoshi T, Nagao Y, Konishi K, Ieiri S, Hong J, Maehara Y, Hashizume M
  • Journal Title: Surg Endosc Volume: 27 Pages: 2178-2184
• [Journal Article] Aurora-B overexpression is correlated with aneuploidy and poor prognosis in non-small cell lung cancer (2013)
  • Author(s): Takeshita M, Koga T, Takayama K, Ijichi K, Yano T, Maehara Y, Nakanishi Y, Sueishi K
  • Journal Title: Lung Cancer Volume: 80 Pages: 85-90
• [Journal Article] Aberrant Expression of Plastin-3 Via Copy Number Gain Induces the Epithelial-Mesenchymal Transition in Circulating Colorectal Cancer Cells (2013)
  • Author(s): Sugimachi K, Yokobori T, Iinuma H, Ueda M, Ueo H, Shinden Y, Eguchi H, udo T, Suzuki A, Maehara Y, Mori M,Mimori K
  • Journal Title: Ann Surg Oncol
• [Journal Article] Multimodal treatment strategy for clinical T3 thoracic esophageal cancer (2013)
  • Author(s): Saeki H, Morita M, Tsuda Y, Hidaka G, Kasagi Y, Kawano H, Otsu H, Ando K, Kimura Y, Oki E, Kusumoto T, Maehara Y
  • Journal Title: Ann Surg Oncol Volume: 20 Pages: 4267-4273
• [Journal Article] Impact of second-line and later cetuximab-containing therapy and KRAS genotypes in patients with metastatic colorectal cancer : a multicenter study in Japan (2013)
  • Author(s): Saeki H, Emi Y, Kumashiro R, Otsu H, Kawano H, Ando K, Ida S, Kimura Y, Tokunaga E, Oki E, Morita M, Shimokawa M, Maehara Y
  • Journal Title: Surg Today
• [Journal Article] Phase II trial of alternating mFOLFOX6 and FOLFIRI regimens in the first-line treatment for unresectable or metastatic colorectal cancer (KSCC0701) (2013)
  • Author(s): Oki E, Emi Y, Akagi Y, Tokunaga S, Sadanaga N, Tanaka T, Ogata Y, Saeki H, Kakeji Y, Baba H, Nishimaki T, Natsugoe S, Shirouzu K, Maehara Y
  • Journal Title: Oncology Volume: 84 Pages: 233-239
• [Journal Article] Dedifferentiated liposarcoma of the spermatic cord with a hemangioendothelioma-like component : a case report and review of the literature (2013)
  • Author(s): Okano S, Yamamoto H, Kono S, Fujii H, Shirabe K, Maehara Y, Oda Y
  • Journal Title: Pathol Res Pract Volume: 209 Pages: 596-604
• [Journal Article] CD4 T cell-mediated masking effects of the immunogenicity of tumor-associated antigens are qualitatively and quantitatively different depending on the individual antigens (2013)
  • Author(s): Okano S, Matsumoto Y, Yoshiya S, Yamashita Y, Harimoto N, Ikegami T, Shirabe K, Harada M, Yoshikai Y, Maehara Y
  • Journal Title: Fukuoka Igaku Zasshi Volume: 104 Pages: 1-14
• [Journal Article] Fas-deficient fully allogeneic dendritic cells administered via an intratumoral injection route show efficient antitumor effects in murine models (2013)
  • Author(s): Okano S, Kondoh H, Toshima T, Nakagawara H, Yoshizumi T, Soejima Y. Shirabe K, Harada M, Yoshikai Y, Maehara Y
  • Journal Title: Fukuoka Igaku Zasshi Volume: 104 Pages: 15-26
• [Journal Article] Podoplanin is expressed at the invasive front of esophageal squamous cell carcinomas and is involved in collective cell invasion (2013)
  • Author(s): Nakashima Y, Yoshinaga K, Kitao H, Ando K, Kimura Y, Saeki H, Oki E, Morita M, Kakeji Y, Hirahashi M, Oda Y, Maehara Y
  • Journal Title: Cancer Sci Volume: 104 Pages: 1718-1725
• [Journal Article] Advances in esophageal surgery in elderly patients with thoracic esophageal cancer (2013)
  • Author(s): Morita M, Otsu H, Kawano H, Kumashiro R, Taketani K, Kimura Y, Saeki H, Ando K, Ida S, Oki E, Tokunaga E, Ikeda T, Kusumoto T, Maehara Y
  • Journal Title: Anticancer Res Volume: 33 Pages: 1641-1647
• [Journal Article] Surgical resection for esophageal cancer synchronously or metachronously associated with head and neck cancer (2013)
  • Author(s): Morita M, Kawano H, Otsu H, Kimura Y, aeki H, Ando K, Ida S, Oki E, Ikeda T, Kusumoto T, Fukushima J, Nakashima T, Maehara Y
  • Journal Title: Ann Surg Oncol Volume: 20 Pages: 2434-2439
• [Journal Article] Decreased roundabout 1 expression promotes development of intrahepatic cholangiocarcinoma (2013)
  • Author(s): Mano Y, Aishima S, Fukuhara T, Tanaka Y, Kubo Y, Motomura T, Toshima T, Iguchi T, Shirabe K, Maehara Y, Oda Y
  • Journal Title: Hum Pathol Volume: 44 Pages: 2419-2426
• [Journal Article] Tumor-associated macrophage promotes tumor progression via STAT3 signaling in hepatocellular carcinoma (2013)
  • Author(s): Mano Y, Aishima S, Fujita N, Tanaka Y, Kubo Y, Motomura T, Taketomi A, Shirabe K, Maehara Y, Oda Y
  • Journal Title: Pathobiology Volume: 80 Pages: 146-154
• [Journal Article] Endovascular aneurysm repair for an abdominal aortic aneurysm and a left ruptured common iliac artery aneurysm in a patient with hepatocellular carcinoma : report of a case (2013)
  • Author(s): Kyuragi R, Matsumoto T, Okadome J, Kawakubo E, Homma K, Iwasa K, Guntani A, Okazaki J, Maehara Y
  • Journal Title: Surg Today
• [Journal Article] Hepatic interferon-gamma-induced protein-10 expression is more strongly associated with liver fibrosis than interleukin-28B single nucleotide polymorphisms in hepatocellular carcinoma resected patients with chronic hepatitis C (2013)
  • Author(s): Konishi H, Shirabe K, Yoshiya S, Ikeda T, Ikegami T, Yoshizumi T, Ikawa-Yoshida A, Motomura T, Fukuhara T, Maehara Y
  • Journal Title: Hepatol Res Volume: 43 Pages: 1139-1147
• [Journal Article] Hepatic vein waveform and splenomegaly predict improvement of prothrombin time after splenectomy in hepatitis C virus-related cirrhotic patients (2013)
  • Author(s): Kinjo N, Nagao Y, Akahoshi T, Masahiro K, Hashimoto N, Uehara H, Kawanaka H, Tomikawa M, Shirabe K, Hashizume M, Maehara Y
  • Journal Title: Hepatol Res Volume: 43 Pages: 933-941
• [Journal Article] Liver regeneration and venous collateral formation in the right lobe living-donor remnant : segmental volumetric analysis and three-dimensional visualization (2013)
  • Author(s): Kayashima H, Shirabe K, Morita K, Hashimoto N, Ikegami T, Yoshizumi T, Soejima Y, Maehara Y
  • Journal Title: Transplantation Volume: 95 Pages: 353-360
• [Journal Article] Use of the SAND balloon catheter in single-incision laparoscopic cholecystectomy for acute cholecystitis (2013)
  • Author(s): Ikegami T, Shirabe K, Yoshizumi T, Kayashima H, Maehara Y
  • Journal Title: Asian JEndosc Surg Volume: 6 Pages: 134-136
• [Journal Article] Obstructing spontaneous major shunt vessels is mandatory to keep adequate portal inflow in living-donor liver transplantation (2013)
  • Author(s): Ikegami T, Shirabe K, Nakagawara H, Yoshizumi T, Toshima T, Soejima Y, Uchiyama H, Yamashita Y, Harimoto N, Maehara Y
  • Journal Title: Transplantation Volume: 95 Pages: 1270-1277
• [Journal Article] Contribution of BubR1 to oxidative stress-induced aneuploidy in p53-deficient cells (2013)
  • Author(s): Ikawa-Yoshida A, Ando K, Oki E, Saeki H, Kumashiro R, Taketani K, Ida S, Tokunaga E, Kitao H, Morita M, Maehara Y
  • Journal Title: Cancer Med Volume: 2 Pages: 447-456
• [Journal Article] Expression of Brachyury gene is a significant prognostic factor for primary lung carcinoma (2013)
  • Author(s): Haro A, Yano T, Kohno M, Yoshida T, Koga T, Okamoto T, Takenoyama M, Maehara Y
  • Journal Title: Ann Surg Oncol Volume: 20 Suppl 3 Pages: S509-516
• [Journal Article] Sarcopenia as a predictor of prognosis in patients following hepatectomy for hepatocellular carcinoma (2013)
  • Author(s): Harimoto N, Shirabe K, Yamashita YI, Ikegami T, Yoshizumi T, Soejima Y, Ikeda T, Maehara Y, Nishie A, Yamanaka T
  • Journal Title: Br JSurg Volume: 100 Pages: 1523-1530
• [Journal Article] Technical evolution of laparoscopic hepatic resection : a single institutional experience (2012)
  • Author(s): Soejima Y, Ikegami T, Ijichi H, Ikeda T, Shirabe K, Yoshizumi T, Uchiyama H, Yamashita Y, Harimoto N, Toshima T, Matsuura H, Okadome K, Maehara Y
  • Journal Title: Fukuoka Igaku Zasshi Volume: 103 Pages: 226-232
• [Journal Article] Surgical management of hepatocellular carcinoma in Child-Pugh class B cirrhotic patients : hepatic resection and/or microwave coagulation therapy versus living donor liver transplantation (2012)
  • Author(s): Harada N, Shirabe K, Ikeda Y, Korenaga D, Takenaka K, Maehara Y
  • Journal Title: Ann Transplant Volume: 17 Pages: 11-20