Papers - Kanai, Takanori

A Colorectal Tumor Organoid Library Demonstrates Progressive Loss of Niche Factor Requirements during Tumorigenesis.

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.

Cell Stem Cell 18 ( 6 ) 827 - 38 2016.06

Joint Work, Accepted

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Colorectal tumor is a heterogeneous disease, with varying clinical presentation and prognosis in patients. To establish a platform encompassing this diversity, we generated 55 colorectal tumor organoid lines from a range of histological subtypes and clinical stages, including rare subtypes. Each line was defined by gene expression signatures and optimized for organoid culture according to niche factor requirements. In vitro and in xenografts, the organoids reproduced the histopathological grade and differentiation capacity of their parental tumors. Notably, we found that niche-independent growth is predominantly associated with the adenoma-carcinoma transition reflecting accumulation of multiple mutations. For matched pairs of primary and metastatic organoids, which had similar genetic profiles and niche factor requirements, the metastasis-derived organoids exhibited higher metastatic capacity. These observations underscore the importance of genotype-phenotype analyses at a single-patient level and the value of our resource to provide insights into colorectal tumorigenesis and patient-centered therapeutic development.

Copyright © 2016 Elsevier Inc. All rights reserved.


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Inhibition of DNA Methylation Suppresses Intestinal Tumor Organoids by Inducing an Anti-Viral Response.

Saito Y, Nakaoka T, Sakai K, Muramatsu T, Toshimitsu K, Kimura M, Kanai T, Sato T, Saito H.

Sci Rep 6 ( 25311 )  2016.05

Joint Work, Accepted

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Recent studies have proposed that the major anti-tumor effect of DNA methylation inhibitors is induction of interferon-responsive genes via dsRNAs-containing endogenous retroviruses. Recently, a 3D culture system for stem cells known as organoid culture has been developed. Lgr5-positive stem cells form organoids that closely recapitulate the properties of original tissues. To investigate the effect of DNA demethylation on tumor organoids, we have established organoids from intestinal tumors of Apc(Min/+) (Min) mice and subjected them to 5-aza-2'-deoxycytidine (5-Aza-CdR) treatment and Dnmt1 knockdown. DNA demethylation induced by 5-Aza-CdR treatment and Dnmt1 knockdown significantly reduced the cell proliferation of the tumor organoids. Microarray analyses of the tumor organoids after 5-Aza-CdR treatment and Dnmt1 knockdown revealed that interferon-responsive genes were activated by DNA demethylation. Gene ontology and pathway analyses clearly demonstrated that these genes activated by DNA demethylation are involved in the anti-viral response. These findings indicate that DNA demethylation suppresses the proliferation of intestinal tumor organoids by inducing an anti-viral response including activation of interferon-responsive genes. Treatment with DNA methylation inhibitors to activate a growth-inhibiting immune response may be an effective therapeutic approach for colon cancers.

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Colonic dysmotility and morphologic abnormality frequently detected in Japanese patients with irritable bowel syndrome

KANAI Takanori

Intestinal Research  2016

Cross-sectional small intestinal surveillance of maintenance hemodialysis patients using video capsule endoscopy:SCHEMA study.

KANAI Takanori

Endosc Int Open 4(5):E589-96. 2016

A Colorectal Tumor Organoid Library Demonstrates Progressive Loss of Niche Factor Requirements during Tumorigenesis

KANAI Takanori

Cell Stem Cell 2;18(6):827-38 2016

Glycolytic pathway affects differentiation of human monocytes to regulatory macrophages

KANAI Takanori

Immunol Lett 176:18-27 2016

The Ulcerative Colitis Endoscopic Index of Severity (UCEIS) is useful to predict medium to long-term prognosis in ulcerative colitis patients with clinical remission.

KANAI Takanori

J Crohns Colitis 10(11):1303-1309 2016

Indole compounds may be promising medicines for ulcerative colitis

KANAI Takanori

J Gastroenterol. 51(9):853-61 2016

Inhibition of DNA Methylation Suppresses Intestinal Tumor Organoids by Inducing an Anti-Viral Response

KANAI Takanori

Sci Rep 4;6:25311 2016

Fatal hemorrhage in a patient with advanced soft tissue sarcoma following radiation and pazopanib treatment: A case report

KANAI Takanori

Oncol Lett 11(4):2408-2410 2016

Ulcerative colitis endoscopic index of severity is associated with long-term prognosis in ulcerative colitis patients treated with infliximab

KANAI Takanori

Dig Endosc 28(6):665-70 2016

Broadband mid-infrared pulses from potassium titanyl arsenate/zinc germanium phosphate optical parametric amplifier pumped by Tm, Ho-fiber-seeded Ho:YAG chirped-pulse amplifier

KANAI Takanori

Opt Lett 1;41(5):930-3 2016

Effects of preoperative proton pump inhibitor administration on bleeding after gastric endoscopic submucosal dissection: A systematic review and meta-analysis

KANAI Takanori

United European Gastroenterol J 4(1):5-10 2016

Clinical Efficacy and Safety of Oral Qing-Dai in Patients with Ulcerative Colitis: A Single-Center Open-Label Prospective Study

KANAI Takanori

Digestion 93(3):193-201 2016

Up-to-date medical treatment for ulcerative colitis

KANAI Takanori

Nihon Shokakibyo Gakkai Zasshi 113(3):413-23 2016

Early tumor cavitation with regorafenib in metastatic colorectal cancer

KANAI Takanori

A case report. Oncol Lett 11(1):231-233 2016

Percutaneous endoscopic gastrostomy under steady pressure automatically controlled endoscopy: First clinical series

KANAI Takanori

World J Gastrointest Endosc 10;8(3):186-91 2016

Simeprevir/pegylated interferon/ribavirin triple therapy for recurrent hepatitis C after living donor liver transplantation

KANAI Takanori

Hepatol Res 46(11):1118-1128 2016

Endoscopic Severity Predicts Long-Term Prognosis in Crohn's Disease Patients with Clinical Remission

KANAI Takanori

Digestion 93(1):66-71 2016

Endoscopic slipknot clip suturing method: an ex vivo feasibility study (with video)

KANAI Takanori

Gastrointest Endosc 83(2):447-50 2016