masanao nasuno - Academia.edu (original) (raw)

Papers by masanao nasuno

Research paper thumbnail of Mesenchymal Stem Cells Cancel Azoxymethane-Induced Tumor Initiation

Stem Cells, Mar 17, 2014

The role of mesenchymal stem cells (MSCs) in tumorigenesis remains controversial. Therefore, our ... more The role of mesenchymal stem cells (MSCs) in tumorigenesis remains controversial. Therefore, our goal was to determine whether exogenous MSCs possess intrinsic antineoplastic or proneoplastic properties in azoxymethane (AOM)-induced carcinogenesis. Three in vivo models were studied: an AOM/dextran sulfate sodium colitis-associated carcinoma model, an aberrant crypt foci model, and a model to assess the acute apoptotic response of a genotoxic carcinogen (AARGC). We also performed in vitro coculture experiments. As a result, we found that MSCs partially canceled AOM-induced tumor initiation but not tumor promotion. Moreover, MSCs inhibited the AARGC in colonic epithelial cells because of the removal of O 6-methylguanine (O 6 MeG) adducts through O 6 MeG-DNA methyltransferase activation. Furthermore, MSCs broadly affected the cell-cycle machinery, potentially leading to G1 arrest in vivo. Coculture of IEC-6 rat intestinal cells with MSCs not only arrested the cell cycle at the G1 phase, but also induced apoptosis. The anti-carcinogenetic properties of MSCs in vitro required transforming growth factor (TGF)-b signaling because such properties were completely abrogated by absorption of TGFb under indirect coculture conditions. MSCs inhibited AOM-induced tumor initiation by preventing the initiating cells from sustaining DNA insults and subsequently inducing G1 arrest in the initiated cells that escaped from the AARGC. Furthermore, tumor initiation perturbed by MSCs might potentially dysregulate WNT and TGF-b-Smad signaling pathways in subsequent tumorigenesis. Obtaining a better understanding of MSC functions in colon carcinogenesis is essential before commencing the broader clinical application of promising MSC-based therapies for cancer-prone patients with inflammatory bowel disease. STEM CELLS 2014;32:913-925

Research paper thumbnail of Highly Bioavailable Curcumin Derivative Ameliorates Crohn’s Disease Symptoms: A Randomized, Double-Blind, Multicenter Study

Journal of Crohn's and Colitis, 2020

Background & AimsThe new curcumin derivative Theracurmin® has a 27–fold higher absorption rate th... more Background & AimsThe new curcumin derivative Theracurmin® has a 27–fold higher absorption rate than natural curcumin powder. Theracurmin® is an inhibitor of nuclear factor-κB, which mediates the expression of inflammatory cytokines. The effect of Theracurmin® on inflammatory bowel disease in humans has not been explored; therefore, we investigated the efficacy and safety of Theracurmin® in patients with Crohn’s disease.MethodsIn this randomized, double-blinded study performed at 5 independent medical centers in Japan, Theracurmin® (360 mg/day, n = 20) or placebo (n = 10) was administered to patients with active mild-to-moderate Crohn’s disease for 12 weeks. The agent’s efficacy was assessed by evaluating clinical and endoscopic remission, healing of anal lesions, and blood levels of inflammatory markers.ResultsIn the Theracurmin® group, a significant reduction in clinical disease activity was observed in week 12 relative to that in week 0 (p = 0.005). On intention-to-treat analysis,...

Research paper thumbnail of Contextual niche signals towards colorectal tumor progression by mesenchymal stem cell in the mouse xenograft model

Journal of gastroenterology, Jan 14, 2015

The role of mesenchymal stem/stromal cells (MSCs) in tumorigenesis remains controversial. This st... more The role of mesenchymal stem/stromal cells (MSCs) in tumorigenesis remains controversial. This study aimed to determine whether heterotypic interactions between MSCs and colon cancer cells can supply contextual signals towards tumor progression. Xenografts consisting of co-implanted human colorectal cancer cells with rat MSCs in immunodeficient mice were evaluated by tumor progression, angiogenic profiles, and MSC fate. Furthermore, we investigated how MSCs function as a cancer cell niche by co-culture experiments in vitro. Tumor growth progressed in two ways, either independent of or dependent on MSCs. Such cell line-specific dependency could not be explained by host immune competency. COLO 320 xenograft angiogenesis was MSC-dependent, but less dependent on vascular endothelial growth factor (VEGF), whereas HT-29 angiogenesis was not MSC-dependent, but was VEGF-dependent. MSCs and COLO 320 cells established a functional positive feedback loop that triggered formation of a cancer ce...

Research paper thumbnail of Mesenchymal Stem Cells Cancel Azoxymethane-Induced Tumor Initiation

Stem Cells, Mar 17, 2014

The role of mesenchymal stem cells (MSCs) in tumorigenesis remains controversial. Therefore, our ... more The role of mesenchymal stem cells (MSCs) in tumorigenesis remains controversial. Therefore, our goal was to determine whether exogenous MSCs possess intrinsic antineoplastic or proneoplastic properties in azoxymethane (AOM)-induced carcinogenesis. Three in vivo models were studied: an AOM/dextran sulfate sodium colitis-associated carcinoma model, an aberrant crypt foci model, and a model to assess the acute apoptotic response of a genotoxic carcinogen (AARGC). We also performed in vitro coculture experiments. As a result, we found that MSCs partially canceled AOM-induced tumor initiation but not tumor promotion. Moreover, MSCs inhibited the AARGC in colonic epithelial cells because of the removal of O 6-methylguanine (O 6 MeG) adducts through O 6 MeG-DNA methyltransferase activation. Furthermore, MSCs broadly affected the cell-cycle machinery, potentially leading to G1 arrest in vivo. Coculture of IEC-6 rat intestinal cells with MSCs not only arrested the cell cycle at the G1 phase, but also induced apoptosis. The anti-carcinogenetic properties of MSCs in vitro required transforming growth factor (TGF)-b signaling because such properties were completely abrogated by absorption of TGFb under indirect coculture conditions. MSCs inhibited AOM-induced tumor initiation by preventing the initiating cells from sustaining DNA insults and subsequently inducing G1 arrest in the initiated cells that escaped from the AARGC. Furthermore, tumor initiation perturbed by MSCs might potentially dysregulate WNT and TGF-b-Smad signaling pathways in subsequent tumorigenesis. Obtaining a better understanding of MSC functions in colon carcinogenesis is essential before commencing the broader clinical application of promising MSC-based therapies for cancer-prone patients with inflammatory bowel disease. STEM CELLS 2014;32:913-925

Research paper thumbnail of Highly Bioavailable Curcumin Derivative Ameliorates Crohn’s Disease Symptoms: A Randomized, Double-Blind, Multicenter Study

Journal of Crohn's and Colitis, 2020

Background & AimsThe new curcumin derivative Theracurmin® has a 27–fold higher absorption rate th... more Background & AimsThe new curcumin derivative Theracurmin® has a 27–fold higher absorption rate than natural curcumin powder. Theracurmin® is an inhibitor of nuclear factor-κB, which mediates the expression of inflammatory cytokines. The effect of Theracurmin® on inflammatory bowel disease in humans has not been explored; therefore, we investigated the efficacy and safety of Theracurmin® in patients with Crohn’s disease.MethodsIn this randomized, double-blinded study performed at 5 independent medical centers in Japan, Theracurmin® (360 mg/day, n = 20) or placebo (n = 10) was administered to patients with active mild-to-moderate Crohn’s disease for 12 weeks. The agent’s efficacy was assessed by evaluating clinical and endoscopic remission, healing of anal lesions, and blood levels of inflammatory markers.ResultsIn the Theracurmin® group, a significant reduction in clinical disease activity was observed in week 12 relative to that in week 0 (p = 0.005). On intention-to-treat analysis,...

Research paper thumbnail of Contextual niche signals towards colorectal tumor progression by mesenchymal stem cell in the mouse xenograft model

Journal of gastroenterology, Jan 14, 2015

The role of mesenchymal stem/stromal cells (MSCs) in tumorigenesis remains controversial. This st... more The role of mesenchymal stem/stromal cells (MSCs) in tumorigenesis remains controversial. This study aimed to determine whether heterotypic interactions between MSCs and colon cancer cells can supply contextual signals towards tumor progression. Xenografts consisting of co-implanted human colorectal cancer cells with rat MSCs in immunodeficient mice were evaluated by tumor progression, angiogenic profiles, and MSC fate. Furthermore, we investigated how MSCs function as a cancer cell niche by co-culture experiments in vitro. Tumor growth progressed in two ways, either independent of or dependent on MSCs. Such cell line-specific dependency could not be explained by host immune competency. COLO 320 xenograft angiogenesis was MSC-dependent, but less dependent on vascular endothelial growth factor (VEGF), whereas HT-29 angiogenesis was not MSC-dependent, but was VEGF-dependent. MSCs and COLO 320 cells established a functional positive feedback loop that triggered formation of a cancer ce...