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

Leucine-rich Alpha-2 Glycoprotein is a Serum Biomarker of Mucosal Healing in Ulcerative Colitis

KANAI Takanori

J Crohns Colitis 11(1):84-91 2016

Polyglycolic acid sheet for closure of esophagobronchial fistula in a patient with Behçet's disease

KANAI Takanori

Gastrointest Endosc. pii S0016-5107(16)30380-7 2016

Rifabutin-based 10-day and 14-day triple therapy as a third-line and fourth-line regimen for Helicobacter pylori eradication: A pilot study

KANAI Takanori

United European Gastroenterol J 4(3):380-7 2016

Successful Pancreatic Duct Stent Placement for Recurrent Pancreatitis in a Patient with Polysplenia with Agenesis of the Dorsal Pancreas and Peutz-Jeghers Syndrome

KANAI Takanori

Intern Med 55(13):1743-6 2016

DIAMOND study group. Adalimumab Monotherapy and a Combination with Azathioprine for Crohn's Disease: A Prospective, Randomized Trial

KANAI Takanori

J Crohns Colitis 10(11):1259-1266 2016

Endoscopic morphological features of ulcerative colitis-associated dysplasia classified according to the SCENIC consensus statement

KANAI Takanori

Gastrointestinal Endoscopy. Pii :S0016-5107(16)30751-9 2016

Characteristics of gastric cancer detected within 1 year after successful eradication of Helicobacter pylori

KANAI Takanori

J Clin Biochem Nutr 59(3):226-230 2016

Long-Term Clinical Course after Conservative and Endoscopic Treatment of Colonic Diverticular Bleeding

KANAI Takanori

Digestion 9;94(4):186-191 2016

Continuous Regional Arterial Infusion of Protease Inhibitors Has No Efficacy in the Treatment of Severe Acute Pancreatitis: A Retrospective Multicenter Cohort Study

KANAI Takanori

Pancreas 46(4):510-517. 2016

Metal stent for refractory post-ES bleeding: Is this the ultimate treatment modality?

KANAI Takanori

Endosc Int Open ;4(12):E1265-E1266 2016

Accuracy of biopsy for the preoperative diagnosis of superficial nonampullary duodenal adenocarcinoma

KANAI Takanori

Gastrointest Endosc. pii S0016-5107(16)30837-9. 2016

Nanoscale Characterization of Interaction of APOBEC3G with RNA

KANAI Takanori

Biochemistry 56(10):1473-1481 2016

Endoscopic morphologic features of ulcerative colitis-associated dysplasia classified according to the SCENIC consensus statement

KANAI Takanori

S0016- 5107(16)30751-9 2016

Endoscopic slip knot clip suturing method: A prospective pilot study (with video)

KANAI Takanori

Gastrointest Endosc. pii S0016-5107(16)30432-1 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