A Comprehensive Approach Encompassing New Therapeutics for Microsatellite-instability Associated Colorectal Neoplasms

• Project/Area Number: 25253080
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: The University of Tokyo
• Principal Investigator: Watanabe Toshiaki 東京大学, 医学部附属病院, 教授 (80210920)
• Co-Investigator(Kenkyū-buntansha): Sato Toshiro 慶應義塾大学, 医学部, 准教授 (70365245)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥43,550,000 (Direct Cost: ¥33,500,000、Indirect Cost: ¥10,050,000); Fiscal Year 2015: ¥8,710,000 (Direct Cost: ¥6,700,000、Indirect Cost: ¥2,010,000); Fiscal Year 2014: ¥14,690,000 (Direct Cost: ¥11,300,000、Indirect Cost: ¥3,390,000); Fiscal Year 2013: ¥20,150,000 (Direct Cost: ¥15,500,000、Indirect Cost: ¥4,650,000)
• Keywords: 大腸癌 / マイクロサテライト不安定性 / オルガノイド / DNAメチル化 / 鋸歯状腺腫 / 次世代シーケンス / マイクロアレイ / 発癌 / 幹細胞 / 遺伝子導入 / メチル化 / 大腸鋸歯状腺腫 / 大腸幹細胞 / エピジェネティクス

Outline of Final Research Achievements

We generated 55 organoid lines from colorectal neoplasms, including serrated lesions and MSI colon cancers, and elaborated their biological properties. The organoids pathophysiologically recapitulated the patient tumors and exhibited unique gene expression and genetic mutation patterns. MSI colon cancers harbored substantial number of non-synonymous mutations, allowing their robust growth in hostile conditions with poor growth factors. Similar property of the MSI colon cancer organodis was observed in the xenograft models, in which the MSI colon cancer organoids displayed significantly higher tumorigenic capacity. These data suggested that the MSI colorectal cancers distinctively differ from the other sporadic colorectal cancers in molecular and biological characters, highlighting the significance of the individual therapeutics toward eradication of the MSI colorectal cancers.

Research Products

• [Journal Article] A Colorectal Tumor Library Demonstrates Progressive Loss of Niche Factor Requirements during Tumorigenesis (2016)
  • Author(s): Fujii M, Shimokawa M, Date S, Takano A, Matano M, Nanki K, Ohta Y, Toshimitsu K, Nakazato Y, Kawasaki K, Uraoka T, Watanabe T, Kanai T, Sato T
  • Journal Title: Cell Stem Cell Volume: 未定
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Outcome of salvage surgery for colorectal cancer initially treated by upfront endoscopic therapy. (2016)
  • Author(s): Nozawa H, Ishihara S, Fujishiro M, Kodashima S, Ohtani K, Yasuda K, Nishikawa T, Tanaka T, Tanaka J, Kiyomatsu T, Kawai K, Hata K, Kazama S, Sunami E, Kitayama J, Watanabe T.
  • Journal Title: Surgery. Volume: 159 Pages: 713-20
  • DOI: 10.1016/j.surg.2015.09.008
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Surveillanace colonoscopy for colitis associated dysplasia and cancer in ulcerative colitis patients. (2016)
  • Author(s): Hata K, Kishikawa J, Anzai H, Shinagawa T, Kazama S, Ishii H, Nozawa H, Kawai K, Kiyomatsu T, Tanaka J, Tanaka T, Nishikawa T, Otani K, Yasuda K, Yamaguchi H, Ishihara S, Sunami E, Kitayama J, Watanabe T.
  • Journal Title: Digestive Endoscopy Volume: 28 Pages: 260-265
  • DOI: 10.1111/den.12505
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Efficient genetic engineering of human intestinal organoids using electroporation. (2015)
  • Author(s): Fujii M, Matano M, Nanki K, Sato T.
  • Journal Title: Nat Protoc. Volume: 10 Pages: 1474-85
  • DOI: 10.1038/nprot.2015.088
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Modeling colorectal cancer using CRISPR-Cas9– mediated engineering of human intestinal organoids (2015)
  • Author(s): Matano M,Date S, Shimokawa M, Takano A, Fujii M, Ohta Y, Watanabe T, Kanai T, Sato T.
  • Journal Title: Nat Med Volume: 21(3) Pages: 256-262
  • DOI: 10.1038/nm.3802
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Phospholipase A2 Group III and Group X Have Opposing Associations with Prognosis in Colorectal Cancer. (2015)
  • Author(s): Kazama S, Kitayama J, Hiyoshi M, Taketomi Y, Murakami M, Nishikawa T, Tanaka T, Tanaka J, Kiyomatsu T, Kawai K, Hata K, Yamaguchi H, Nozawa H, Ishihara S, Sunami E, Watanabe T.
  • Journal Title: Anticancer Res. Volume: 35 Pages: 2983-90
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Initial safety report on the tolerability of modified FOLFOX6 as adjuvant therapy in patients with curatively resected stage II or III colon cancer (JFMC41-1001-C2: JOIN trial). (2015)
  • Author(s): Kotaka M, Yoshino T, Oba K, Shinozaki K, Touyama T, Manaka D, Matsui T, Ishigure K, Hasegawa J, Inoue K, Goto K, Sakamoto J, Saji S, Ohtsu A, Watanabe T.
  • Journal Title: Cancer Chemother Pharmacol. Volume: 76 Pages: 75-84
  • DOI: 10.1007/s00280-015-2757-0
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] High RAD54B expression: an independent predictor of postoperative distant recurrence in colorectal cancer patients. (2015)
  • Author(s): Nagai Y, Yamamoto Y, Yasuhara T, Hata K, Nishikawa T, Tanaka T, Tanaka J, Kiyomatsu T, Kawai K, Nozawa H, Kazama S, Yamaguchi H, Ishihara S, Sunami E, Yamanaka T, Miyagawa K, Watanabe T.
  • Journal Title: Oncotarget Volume: 6 Pages: 21064-73
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Prognostic Impact of Histologic Type in Curatively Resected Stage IV Colorectal Cancer: A Japanese Multicenter Retrospective Study. (2015)
  • Author(s): Shibata J, Kawai K, Nishikawa T, Tanaka T, Tanaka J, Kiyomatsu T, Hata K, Nozawa H, Kazama S, Yamaguchi H, Ishihara S, Sunami E, Kitayama J, Sugihara K, Watanabe T.
  • Journal Title: Ann Surg Oncol Volume: Suppl 3
  • DOI: 10.1245/s10434-015-4846-z
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] CD133 Expression in Lymph Node Metastases Is Associated with Tumor Aggressiveness During Lymph Node Metastasis in Colorectal Cancer. (2015)
  • Author(s): Kazama S, Kishikawa J, Yasuda K, Otani K, Nishikawa T, Tanaka T, Tanaka J, Kiyomatsu T, Kawai K, Hata K, Nozawa H, Yamaguchi H, Ishihara S, Sunami E, Watanabe T.
  • Journal Title: Anticancer Res Volume: 35 Pages: 6599-605
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Predictors and outcome of complete removal of colorectal cancer with synchronous lung metastases. (2015)
  • Author(s): Nozawa H, Tanaka J, Nishikawa T, Tanaka T, Kiyomatsu T, Kawai K, Hata K, Kazama S, Yamaguchi H, Ishihara S, Sunami E, Kitayama J, Nakajima J, Kokudo N, Watanabe T.
  • Journal Title: Mol Clin Oncol Volume: 3 Pages: 1041-1047
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] A multicenter phase II study of preoperative chemoradiotherapy with S-1 plus oxaliplatin for locally advanced rectal cancer (SHOGUN trial). (2015)
  • Author(s): Matsusaka S, Ishihara S, Kondo K, Horie H, Uehara K, Oguchi M, Murofushi K, Ueno M, Mizunuma N, Shimbo T, Kato D, Okuda J, Hashiguchi Y, Nakazawa M, Sunami E, Kawai K, Yamashita H, Okada T, Ishikawa Y, Nakajima T, Watanabe T.
  • Journal Title: Radiother Oncol Volume: 116 Pages: 209-13
  • DOI: 10.1016/j.radonc.2015.08.002
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Recent advances in robotic surgery for rectal cancer. (2015)
  • Author(s): Ishihara S, Otani K, Yasuda K, Nishikawa T, Tanaka J, Tanaka T, Kiyomatsu T, Hata K, Kawai K, Nozawa H, Kazama S, Yamaguchi H, Sunami E, Kitayama J, Watanabe T.
  • Journal Title: Int J Clin Oncol Volume: 20 Pages: 633-40
  • DOI: 10.1007/s10147-015-0854-z
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] The preoperative platelet to lymphocyte ratio is a prognostic marker in patients with stage II colorectal cancer. (2015)
  • Author(s): Ozawa T, Ishihara S, Nishikawa T, Tanaka T, Tanaka J, Kiyomatsu T, Hata K, Kawai K, Nozawa H, Kazama S, Yamaguchi H, Sunami E, Kitayama J, Watanabe T.
  • Journal Title: Int J Colorectal Dis Volume: 30 Pages: 1165-71
  • DOI: 10.1007/s00384-015-2276-9
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Analysis of anastomotic leakage after rectal surgery: A case-control study. (2015)
  • Author(s): Tanaka J, Nishikawa T, Tanaka T, Kiyomatsu T, Hata K, Kawai K, Kazama S, Nozawa H, Yamaguchi H, Ishihara S, Sunami E, Kitayama J, Watanabe T.
  • Journal Title: Ann Med Surg Volume: 11 Pages: 183-6
  • DOI: 10.1016/j.amsu.2015.05.002
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Prediction of the preoperative chemoradiotherapy response for rectal cancer by peripheral blood lymphocyte subsets. (2015)
  • Author(s): Tada N, Kawai K, Tsuno NH, Ishihara S, Yamaguchi H, Sunami E, Kitayama J, Oba K, Watanabe T.
  • Journal Title: World J Surg Oncol Volume: 13 Pages: 30-30
  • DOI: 10.1186/s12957-014-0418-0
  • Peer Reviewed
• [Journal Article] Phosphatidylserine-specific phospholipase A1 (PS-PLA1) expression in colorectal cancer correlates with tumor invasion and hematogenous metastasis. (2015)
  • Author(s): Iida Y, Sunami E, Yamashita H, Hiyoshi M, Ishihara S, Yamaguchi H, Inoue A, Makide K, Tsuno NH, Aoki J, Kitayama J, Watanabe T.
  • Journal Title: Anticancer Res. Volume: 35 Pages: 1459-64
  • Peer Reviewed
• [Journal Article] Log odds of positive lymph nodes as a prognostic indicator in stage IV colorectal cancer patients undergoing curative resection. (2015)
  • Author(s): Ozawa T, Ishihara S, Sunami E, Kitayama J, Watanabe T.
  • Journal Title: J Surg Oncol Volume: 111 Pages: 465-71
  • DOI: 10.1002/jso.23855
  • Peer Reviewed
• [Journal Article] A phase I dose escalation study of oxaliplatin plus oral S-1 and pelvic radiation in patients with locally advanced rectal cancer (SHOGUN trial). (2015)
  • Author(s): Ishihara S, Matsusaka S, Kondo K, Horie H, Uehara K, Oguchi M, Murofushi K, Ueno M, Mizunuma N, Shinbo T, Kato D, Okuda J, Hashiguchi Y, Nakazawa M, Sunami E, Kawai K, Yamashita H, Okada T, Ishikawa Y, Nakajima T, Watanabe T.
  • Journal Title: Radiat Oncol Volume: 10 Pages: 24-24
  • DOI: 10.1186/s13014-015-0333-8
  • Peer Reviewed
• [Journal Article] Prognostic significance of the lymph node ratio in stage IV colorectal cancer patients who have undergone curative resection. (2015)
  • Author(s): Ozawa T, Ishihara S, Nishikawa T, Tanaka T, Tanaka J, Kiyomatsu T, Hata K, Kawai K, Nozawa H, Kanazawa T, Kazama S, Yamaguchi H, Sunami E, Kitayama J, Watanabe T.
  • Journal Title: Ann Surg Oncol Volume: 22 Pages: 1513-9
  • DOI: 10.1245/s10434-014-4184-6
  • Peer Reviewed
• [Journal Article] Nomogram prediction of metachronous colorectal neoplasms in patients with colorectal cancer. (2015)
  • Author(s): Kawai K, Ishihara S, Yamaguchi H, Sunami E, Kitayama J, Miyata H, Watanabe T.
  • Journal Title: Ann Surg Volume: 261 Pages: 926-32
  • DOI: 10.1097/sla.0000000000000881
  • Peer Reviewed
• [Journal Article] Detection of carcinoembryonic antigen mRNA in peritoneal lavage by the transcription-reverse transcription concerted method indicates poor prognosis in patients with stage II and III colon cancer. (2015)
  • Author(s): Murono K, Kazama S, Yamaguchi H, Kawai K, Ishihara S, Sunami E, Kitayama J, Satoh Y, Kurihara M, Yatomi Y, Watanabe T.
  • Journal Title: Surgery. Volume: 157 Pages: 322-30
  • DOI: 10.1016/j.surg.2014.09.015
  • Peer Reviewed
• [Journal Article] Incidence and prognostic significance of positive peritoneal lavage in colorectal cancer. (2015)
  • Author(s): Nishikawa T, Sunami E, Tanaka T, Tanaka J, Kiyomatsu T, Kawai K, Hata K, Kazama S, Nozawa H, Ishihara S, Watanabe T.
  • Journal Title: Surg Today Volume: Epub ahead of print
  • Peer Reviewed
• [Journal Article] Characteristics and prognosis of colorectal cancer associated with rheumatic disease. (2015)
  • Author(s): Kishikawa J, Kawai K, Tsuno N, Yamaguchi H, Ishihara S, Sunami E, Watanabe T.
  • Journal Title: Int Surg Volume: Epub ahead of print
  • Peer Reviewed
• [Journal Article] Prognostic impact of primary tumor resection and lymph node dissection in stage IV colorectal cancer with unresectable metastasis: a propensity score analysis in a multicenter retrospective study. (2014)
  • Author(s): Ishihara S, Hayama T, Yamada H, Nozawa K, Matsuda K, Miyata H, Yoneyama S, Tanaka T, Tanaka J, Kiyomatsu T, Kawai K, Nozawa H, Kanazawa T, Kazama S, Yamaguchi H, Sunami E, Kitayama J, Hashiguchi Y, Sugihara K, Watanabe T.
  • Journal Title: Ann Surg Oncol. Volume: 21 Pages: 2949-55
  • DOI: 10.1245/s10434-014-3719-1
  • Peer Reviewed / Open Access
• [Journal Article] Nuclear Notch3 Expression is Associated with Tumor Recurrence in Patients with Stage II and III Colorectal Cancer (2014)
  • Author(s): Ozawa T, Kazama S, Akiyoshi T, Murono K, Yoneyama S, Tanaka T, Tanaka J, Kiyomatsu T, Kawai K, Nozawa H, Kanazawa T, Yamaguchi H, Ishihara S, Sunami E, Kitayama J, Morikawa T, Fukayama M, Watanabe T.
  • Journal Title: Ann Surg Oncol Volume: 21 Pages: 2650-8
  • DOI: 10.1245/s10434-014-3659-9
  • Peer Reviewed
• [Journal Article] Prediction of response to preoperative chemoradiotherapy in rectal cancer by using reverse transcriptase polymerase chain reaction analysis of four genes (2014)
  • Author(s): Watanabe T, Kobunai T, Akiyoshi T, Matsuda K, Ishihara S, Nozawa K.
  • Journal Title: Dis Colon Rectum Volume: 57(1) Pages: 23-31
  • DOI: 10.1097/01.dcr.0000437688.33795.9d
  • Peer Reviewed
• [Journal Article] Changes in the plasma levels of cytokines/chemokines for predicting the response to chemoradiation therapy in rectal cancer patients. (2014)
  • Author(s): Tada N, Tsuno NH, Kawai K, Murono K, Nirei T, Ishihara S, Sunami E, Kitayama J, Watanabe T.
  • Journal Title: Oncol Rep. Volume: 31 Pages: 463-71
  • DOI: 10.3892/or.2013.2857
  • Peer Reviewed / Open Access
• [Journal Article] KLF5 Regulates the Integrity and Oncogenicity of Intestinal Stem Cells. (2014)
  • Author(s): Nakaya T, Ogawa S, Manabe I, Tanaka M, Sanada M, Sato T, Taketo MM, Nakao K, Clevers H, Fukayama M, Kuroda M, Nagai R.
  • Journal Title: Cancer Res Volume: Epub ahead of print
  • Peer Reviewed
• [Journal Article] Macrophages and Dendritic Cells Emerge in the Liver during Intestinal Inflammation and Predispose the Liver to Inflammation (2014)
  • Author(s): Mikami Y, Mizuno S, Nakamoto N, Hayashi A, Sujino T, Sato T, Kamada N, Matsuoka K, Hisamatsu T, Ebinuma H, Hibi T, Yoshimura A, Kanai T.
  • Journal Title: PLoS One. Volume: 9 Pages: 1-1
  • DOI: 10.1371/journal.pone.0084619
  • Peer Reviewed
• [Journal Article] Clinical benefit of surgery for stage IV colorectal cancer with synchronous peritoneal metastasis. (2014)
  • Author(s): Kobayashi H, Kotake K, Funahashi K, Hase K, Hirata K, Iiai T, Kameoka S, Kanemitsu Y, Maeda K, Murata A, Ohue M, Shirouzu K, Takahashi K, Watanabe T, Yano H, Yatsuoka T, Hashiguchi Y, Sugihara K
  • Journal Title: J Gastroenterology Volume: 49(4) Pages: 646-54
  • DOI: 10.1007/s00535-013-0820-3
  • Peer Reviewed
• [Journal Article] Salvage Gastrectomy After Intravenous and Intraperitoneal Paclitaxel (PTX) Administration with Oral S-1 for Peritoneal Dissemination of Advanced Gastric Cancer with Malignant Ascites. (2014)
  • Author(s): Kitayama J, Ishigami H, Yamaguchi H, Yamashita H, Emoto S, Kaisaki S, Watanabe T.
  • Journal Title: Ann Surg Oncol Volume: 21 Pages: 539-46
  • DOI: 10.1245/s10434-013-3208-y
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] CD90(+) mesothelial-like cells in peritoneal fluid promote peritoneal metastasis by forming a tumor permissive microenvironment. (2014)
  • Author(s): Kitayama J
  • Journal Title: PloS One Volume: 21;9(1)
  • DOI: 10.1371/journal.pone.0086516
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Flow cytometric quantification of intraperitoneal free tumor cells (FTC) in patients with peritoneal metastasis. (2014)
  • Author(s): Kitayama J, Emoto S, Yamaguchi H, Ishigami H, Kamei T, Yamashita H, Seto Y, Matsuzaki K, Watanabe T.
  • Journal Title: Cytometry B Clin Cytom. Volume: 86 Pages: 56-62
  • DOI: 10.1002/cyto.b.21126
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• [Journal Article] Colorectal cancer and hypercoagulability. (2014)
  • Author(s): Kawai K, Watanabe T.
  • Journal Title: Surg Today Volume: 44(5) Pages: 797-803
  • DOI: 10.1007/s00595-013-0606-5
  • Peer Reviewed
• [Journal Article] Thrombocytosis before pre-operative chemoradiotherapy predicts poor response and shorter local recurrence-free survival in rectal cancer. (2014)
  • Author(s): Kawai K.
  • Journal Title: Int J Colorectal Dis Volume: 28(4):527 Pages: 527-35
  • DOI: 10.1007/s00384-012-1594-4
  • Peer Reviewed
• [Journal Article] Intraperitoneal administration of cisplatin via an in situ cross-linkable hyaluronic acid-based hydrogel for peritoneal dissemination of gastric cancer (2014)
  • Author(s): Emoto S, Yamaguchi H, Kamei T, Ishigami H, Suhara T, Suzuki Y, Ito T, Kitayama J, Watanabe T.
  • Journal Title: Sugery Today Volume: 44 Pages: 919-26
  • DOI: 10.1007/s00595-013-0674-6
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Selective lateral pelvic lymph node dissection in patients with advanced low rectal cancer treated with preoperative chemoradiotherapy based on the pretreatment imaging (2014)
  • Author(s): Akiyoshi T, Ueno M, Matsueda K, Konishi T, Fujimoto Y, Nagayama S, Fukunaga Y, Unno T, Kano A, Kuroyanagi H, Oya M, Yamaguchi T, Watanabe T, Muto T.
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  • DOI: 10.1245/s10434-013-3216-y
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• [Journal Article] Unlimited in vitro expansion of adult bi-potent pancreas progenitors through the Lgr5/R-spondin axis (2013)
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  • Journal Title: EMBO J Volume: 32(20) Pages: 2708-21
  • DOI: 10.1038/emboj.2013.204
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• [Journal Article] A single strain of Clostridium butyricum induces intestinal IL-10-producing macrophages to suppress acute experimental colitis in mice. (2013)
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  • Journal Title: Cell Host Microbe. Volume: 13 Pages: 711-22
  • DOI: 10.1016/j.chom.2013.05.013
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• [Journal Article] Growing self-organizing mini-guts from a single intestinal stem cell : mechanism and applications (2013)
  • Author(s): Sato T, Clevers H.
  • Journal Title: Science Volume: 340(6137) Pages: 1190-4
  • DOI: 10.1126/science.1234852
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• [Journal Article] IL-22-producing RORγt-dependent innate lymphoid cells play a novel protective role in murine acute hepatitis (2013)
  • Author(s): Matsumoto A, Kanai T, Mikami Y, Chu PS, Nakamoto N, Ebinuma H, Saito H, Sato T, Yagita H, Hibi T.
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  • DOI: 10.1371/journal.pone.0062853
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• [Journal Article] In vitro expansion of single Lgr5+ liver stem cells induced by Wnt-driven regeneration. (2013)
  • Author(s): Huch M, Dorrell C, Boj SF, van Es JH, Li VSW, van de Wetering M, Sato T, Hamer K, Sasaki N, Finegold MJ, Haft A, Vries R, Grompe M, Clevers H.
  • Journal Title: Nature Volume: 494(7436) Pages: 247-50
  • DOI: 10.1038/nature11826
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• [Journal Article] A phase 2 trial of intravenous and intraperitoneal paclitaxel combined with S-1 for treatment of gastric cancer with macroscopic peritoneal metastasis. (2013)
  • Author(s): Yamaguchi H, Kitayama J, Ishigami H, Emoto S, Yamashita H, Watanabe T.
  • Journal Title: Cancer Volume: 119 Pages: 3354-8
  • DOI: 10.1002/cncr.28204
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• [Journal Article] KRAS Mutational Status in Japanese Patients with Colorectal Cancer: Results from a Nationwide, Multicenter, Cross-sectional Study. (2013)
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  • DOI: 10.1093/jjco/hyt062
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• [Journal Article] Hepatic steatosis is associated with lower incidence of liver metastasis from colorectal cancer. (2013)
  • Author(s): Murono K, Kitayama J, Tsuno NH, Nozawa H, Kawai K, Sunami E, Akahane M, Watanabe T.
  • Journal Title: Int J Colorectal Dis Volume: 28(8) Pages: 1065-1072
  • DOI: 10.1007/s00384-013-1656-2
  • Peer Reviewed
• [Journal Article] Hypoxia enhances colon cancer migration and invasion through promotion of epithelial-mesenchymal transition. (2013)
  • Author(s): Hongo K, Tsuno NH, Kawai K, Sasaki K, Kaneko M, Hiyoshi M, Murono K, Tada N, Nirei T, Sunami E, Takahashi K, Nagawa H, Kitayama J, Watanabe T.
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  • Peer Reviewed