Updated on 2022/01/04

写真a

 
SUNAGAWA Masaki
 
Organization
Graduate School of Medicine Department of Surgery, Division of Perioperative Medicine Endowed Chair Designated assistant professor
Title
Designated assistant professor
Contact information
メールアドレス

Degree 2

  1. 博士(医学) ( 2017.3   名古屋大学 ) 

  2. 学士(医学) ( 2005.3   島根大学 ) 

Research Interests 5

  1. Retroperitoneal sarcoma

  2. Pancreatic cancer

  3. Translational research

  4. Surgical Oncology

  5. Metabolomics

Research Areas 4

  1. Life Science / Digestive surgery

  2. Life Science / Tumor diagnostics and therapeutics

  3. Life Science / Laboratory animal science

  4. Life Science / Biomaterials

Current Research Project and SDGs 2

  1. 希少癌早期発見パネルの開発

  2. アシドーシス環境下における癌悪性化機構の解明と新規治療方針の開発

Research History 2

  1. Nagoya University Graduate School of Medicine   Division of preoperative surgery, division of surgery   Designated assistant professor

    2021.4

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    Country:Japan

  2. Columbia University Irving cancer research center   Division of digestive disease

    2017.5 - 2020.3

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    Country:United States

Education 2

  1. Nagoya University   School of Medicine

    2013.4 - 2017.3

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    Country: Japan

  2. Shimane University

    1999.4 - 2005.3

Professional Memberships 14

  1. 日本外科学会

  2. 日本消化器外科学会

  3. 日本癌学会

  4. 日本臨床外科学会

  5. 日本消化器外科学会   専門医・指導医

    2012.4

  6. 日本外科学会   専門医

    2005.4

  7. American Pancreatic Association

  8. 日本サルコーマ治療研究学会

  9. 日本内視鏡外科学会

  10. 日本癌治療学会

  11. 日本肝胆膵外科学会

  12. 日本胆道学会

  13. 日本膵臓学会

  14. 日本臨床腫瘍学会

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Awards 1

  1. 47th Young Investigator awards

    2016.10   47th American Pancreatic Association   TFF1 might inhibit invasion but accelerate lymph node metastasis of pancreatic ductal adenocarcinoma

 

Papers 7

  1. Anti-Malignant Effect of Tensile Loading to Adherens Junctions in Cutaneous Squamous Cell Carcinoma Cells. International journal

    Oleg Dobrokhotov, Masaki Sunagawa, Takeru Torii, Shinji Mii, Keiko Kawauchi, Atsushi Enomoto, Masahiro Sokabe, Hiroaki Hirata

    Frontiers in cell and developmental biology   Vol. 9   page: 728383 - 728383   2021.11

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    Language:Japanese   Publishing type:Research paper (scientific journal)  

    Actomyosin contractility regulates various cellular processes including proliferation and differentiation while dysregulation of actomyosin activity contributes to cancer development and progression. Previously, we have reported that actomyosin-generated tension at adherens junctions is required for cell density-dependent inhibition of proliferation of normal skin keratinocytes. However, it remains unclear how actomyosin contractility affects the hyperproliferation ability of cutaneous squamous cell carcinoma (cSCC) cells. In this study, we find that actomyosin activity is impaired in cSCC cells both in vitro and in vivo. External application of tensile loads to adherens junctions by sustained mechanical stretch attenuates the proliferation of cSCC cells, which depends on intact adherens junctions. Forced activation of actomyosin of cSCC cells also inhibits their proliferation in a cell-cell contact-dependent manner. Furthermore, the cell cycle arrest induced by tensile loading to adherens junctions is accompanied by epidermal differentiation in cSCC cells. Our results show that the degree of malignant properties of cSCC cells can be reduced by applying tensile loads to adherens junctions, which implies that the mechanical status of adherens junctions may serve as a novel therapeutic target for cSCC.

    DOI: 10.3389/fcell.2021.728383

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  2. Interleukin-1β-induced pancreatitis promotes pancreatic ductal adenocarcinoma via B lymphocyte-mediated immune suppression. International journal

    Ryota Takahashi, Marina Macchini, Masaki Sunagawa, Zhengyu Jiang, Takayuki Tanaka, Giovanni Valenti, Bernhard W Renz, Ruth A White, Yoku Hayakawa, C Benedikt Westphalen, Yagnesh Tailor, Alina C Iuga, Tamas A Gonda, Jeanine Genkinger, Kenneth P Olive, Timothy C Wang

    Gut   Vol. 70 ( 2 ) page: 330 - 341   2021.2

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    Language:English   Publishing type:Research paper (scientific journal)  

    OBJECTIVE: Long-standing chronic pancreatitis is an established risk factor for pancreatic ductal adenocarcinoma (PDAC). Interleukin-1β (IL-1β) has been associated in PDAC with shorter survival. We employed murine models to investigate the mechanisms by which IL-1β and chronic pancreatitis might contribute to PDAC progression. DESIGN: We crossed LSL-Kras +/G12D;Pdx1-Cre (KC) mice with transgenic mice overexpressing IL-1β to generate KC-IL1β mice, and followed them longitudinally. We used pancreatic 3D in vitro culture to assess acinar-to-ductal metaplasia formation. Immune cells were analysed by flow cytometry and immunohistochemical staining. B lymphocytes were adoptively transferred or depleted in Kras-mutant mice. B-cell infiltration was analysed in human PDAC samples. RESULTS: KC-IL1β mice developed PDAC with liver metastases. IL-1β treatment increased Kras+/G12D pancreatic spheroid formation. CXCL13 expression and B lymphocyte infiltration were increased in KC-IL1β pancreata. Adoptive transfer of B lymphocytes from KC-IL1β mice promoted tumour formation, while depletion of B cells prevented tumour progression in KC-IL1β mice. B cells isolated from KC-IL1β mice had much higher expression of PD-L1, more regulatory B cells, impaired CD8+ T cell activity and promoted tumorigenesis. IL-35 was increased in the KC-IL1β pancreata, and depletion of IL-35 decreased the number of PD-L1+ B cells. Finally, in human PDAC samples, patients with PDAC with higher B-cell infiltration within tumours showed significantly shorter survival. CONCLUSION: We show here that IL-1β promotes tumorigenesis in part by inducing an expansion of immune-suppressive B cells. These findings point to the growing significance of B suppressor cells in pancreatic tumorigenesis.

    DOI: 10.1136/gutjnl-2019-319912

    PubMed

  3. Is constant negative pressure for external drainage of the main pancreatic duct useful in preventing pancreatic fistula following pancreatoduodenectomy? International journal

    Masaki Sunagawa, Yukihiro Yokoyama, Junpei Yamaguchi, Tomoki Ebata, Gen Sugawara, Tsuyoshi Igami, Takashi Mizuno, Masato Nagino

    Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.]   Vol. 19 ( 4 ) page: 602 - 607   2019.6

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    Language:Japanese   Publishing type:Research paper (scientific journal)  

    BACKGROUND: This study sought to investigate the utility of constant negative pressure for external drainage of the main pancreatic duct in preventing postoperative pancreatic fistula (POPF) after pancreatoduodenectomy. METHODS: Only patients with soft pancreas were included. In the former period (July 2013 to May 2015), gravity dependent drainage was applied (gravity dependent drainage group), and in the latter period (June 2015 to November 2016), constant negative pressure drainage (negative pressure drainage group) was applied to the main pancreatic duct stent. RESULTS: There were 37 patients in the gravity dependent drainage group and 39 patients in the negative pressure drainage group. Clinically relevant POPF occurred in 21 patients (56.8%) in the gravity dependent drainage group and 13 patients (33.3%) in the negative pressure drainage group (p = 0.040). The incidence rate of major complications (Clavien-Dindo grade > III) was significantly lower in the negative pressure drainage group (13.2%) compared to the gravity dependent drainage group (48.7%) (p = 0.001). In-hospital stay was also significantly shorter in the negative pressure drainage group compared to the gravity dependent drainage group (median 25 vs. 33 days, p = 0.024). Multivariate analysis demonstrated that the gravity dependent drainage was one of the independent risk factors for the incidence of POPF (odds ratio, 3.33; p = 0.032). CONCLUSIONS: In patients with soft pancreas, the incidence rate of clinically relevant POPF may be reduced by applying constant negative pressure to the pancreatic duct stent. It also has a potential to reduce overall incidence of major complications and shorten in-hospital stay after pancreatoduodenectomy.

    DOI: 10.1016/j.pan.2019.04.002

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  4. Cholinergic Signaling via Muscarinic Receptors Directly and Indirectly Suppresses Pancreatic Tumorigenesis and Cancer Stemness. International journal

    Bernhard W Renz, Takayuki Tanaka, Masaki Sunagawa, Ryota Takahashi, Zhengyu Jiang, Marina Macchini, Zahra Dantes, Giovanni Valenti, Ruth A White, Moritz A Middelhoff, Matthias Ilmer, Paul E Oberstein, Martin K Angele, Huan Deng, Yoku Hayakawa, C Benedikt Westphalen, Jens Werner, Helen Remotti, Maximilian Reichert, Yagnesh H Tailor, Karan Nagar, Richard A Friedman, Alina C Iuga, Kenneth P Olive, Timothy C Wang

    Cancer discovery   Vol. 8 ( 11 ) page: 1458 - 1473   2018.11

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    Language:English   Publishing type:Research paper (scientific journal)  

    In many solid tumors, parasympathetic input is provided by the vagus nerve, which has been shown to modulate tumor growth. However, whether cholinergic signaling directly regulates progression of pancreatic ductal adenocarcinoma (PDAC) has not been defined. Here, we found that subdiaphragmatic vagotomy in LSL-Kras +/G12D;Pdx1-Cre (KC) mice accelerated PDAC development, whereas treatment with the systemic muscarinic agonist bethanechol restored the normal KC phenotype, thereby suppressing the accelerated tumorigenesis caused by vagotomy. In LSL-Kras +/G12D;LSL-Trp53 +/R172H;Pdx1-Cre mice with established PDAC, bethanechol significantly extended survival. These effects were mediated in part through CHRM1, which inhibited downstream MAPK/EGFR and PI3K/AKT pathways in PDAC cells. Enhanced cholinergic signaling led to a suppression of the cancer stem cell (CSC) compartment, CD11b+ myeloid cells, TNFα levels, and metastatic growth in the liver. Therefore, these data suggest that cholinergic signaling directly and indirectly suppresses growth of PDAC cells, and therapies that stimulate muscarinic receptors may be useful in the treatment of PDAC.Significance: Subdiaphragmatic vagotomy or Chrm1 knockout accelerates pancreatic tumorigenesis, in part via expansion of the CSC compartment. Systemic administration of a muscarinic agonist suppresses tumorigenesis through MAPK and PI3K/AKT signaling, in early stages of tumor growth and in more advanced, metastatic disease. Therefore, CHRM1 may represent a potentially attractive therapeutic target. Cancer Discov; 8(11); 1458-73. ©2018 AACR. This article is highlighted in the In This Issue feature, p. 1333.

    DOI: 10.1158/2159-8290.CD-18-0046

    PubMed

  5. Trefoil factor family 1 expression in the invasion front is a poor prognostic factor associated with lymph node metastasis in pancreatic cancer

    Sunagawa Masaki, Yamaguchi Junpei, Kokuryo Toshio, Ebata Tomoki, Yokoyama Yukihiro, Sugawara Gen, Nagino Masato

    PANCREATOLOGY   Vol. 17 ( 5 ) page: 782 - 787   2017

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    Language:Japanese   Publisher:Pancreatology  

    Objectives Trefoil Factor Family protein 1 (TFF1) is secreted from mucus-producing cells. The relationship between TFF1 expression and clinical outcome in pancreatic ductal adenocarcinoma (PDAC) remains unknown. We aimed to evaluate the prognostic significance of TFF1 expression in PDAC. Methods TFF1 expression was examined on paraffin-embedded sections from 91 patients with resected PDAC using immunohistochemistry. The relationships between TFF1 expression and clinicopathological features were analyzed. Results Among 91 PDAC patients, 71 patients (79.7%) showed TFF1 expression in cancer cells. In a subgroup of 71 patients, TFF1 expression was predominantly observed in the central part of the tumor, whereas TFF1 expression in the invasion front was reduced in 33 patients (46.4%). A significant correlation between preserved TFF1 expression in the invasion front and lymph node metastasis was observed. Univariate survival analysis revealed that preserved TFF1 expression in the invasion front, positive lymphatic invasion, lymph node metastasis and R1 resection was a significant poor prognostic factor in TFF1-positive PDAC patients. Conclusions TFF1 expression is frequently lost or decreased in the invasion front of human PDAC, and preserved TFF1 expression in the invasion front might predict poor survival in patients with PDAC.

    DOI: 10.1016/j.pan.2017.07.188

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  6. Suppression of skin tumorigenesis in CD109-deficient mice. International journal

    Masaki Sunagawa, Shinji Mii, Atsushi Enomoto, Takuya Kato, Yoshiki Murakumo, Yukihiro Shiraki, Naoya Asai, Masato Asai, Masato Nagino, Masahide Takahashi

    Oncotarget   Vol. 7 ( 50 ) page: 82836 - 82850   2016.12

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    Language:Japanese   Publishing type:Research paper (scientific journal)  

    CD109 is a glycosylphosphatidylinositol-anchored glycoprotein that is highly expressed in several types of human cancers, particularly squamous cell carcinomas. We previously reported that CD109-deficient mice exhibit epidermal hyperplasia and chronic skin inflammation. Although we found that CD109 regulates differentiation of keratinocytes in vivo, the function of CD109 in tumorigenesis remains unknown. In this study, we investigated the role of CD109 in skin tumorigenesis using a two-stage carcinogenesis model in CD109-deficient mice with chronic skin inflammation. Immunohistochemical analysis revealed a higher level of TGF-β protein expression in the dermis of CD109-deficient mice than in that of wild-type mice. Additionally, immunofluorescence analysis showed that Smad2 phosphorylation and Nrf2 expression were enhanced in primary keratinocytes from CD109-deficient mice compared with in those from wild-type mice. Although no significant difference was found in conversion rates from papilloma to carcinoma between wild-type and CD109-deficient mice in the carcinogenesis model, we observed fewer and smaller papillomas in CD109-deficient mice than in wild-type mice. Apoptosis and DNA damage marker levels were significantly reduced in CD109-deficient skin compared with in wild-type skin at 24 h after 7, 12-dimethylbenz (α) anthracene treatment. Furthermore, mutation-specific PCR revealed that the mutation frequency of the H-ras gene was less in CD109-deficient skin than in wild-type skin in this model. These results suggest that CD109 deficiency suppresses skin tumorigenesis by enhancing TGF-β/Smad/Nrf2 pathway activity and decreasing the mutation frequency of the H-ras gene.

    DOI: 10.18632/oncotarget.12653

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  7. TFF1 Might Inhibit Invasion but Accelerate Lymph Node Metastasis of Pancreatic Ductal Adenocarcinoma

    Sunagawa M., Yamaguchi J., Yokoyama Y., Kokuryo T., Nagino M.

    PANCREAS   Vol. 45 ( 10 ) page: 1540 - 1540   2016.11

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    Language:Japanese  

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Presentations 1

  1. 後腹膜肉腫初回手術後再発症例の治療選択

    砂川真輝, 横山幸浩, 伊神剛, 水野隆史, 山口淳平, 尾上俊介, 渡辺伸元, 江畑智希

    第59回日本がん治療学会学術集会  2021.10.23 

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    Event date: 2021.10

    Language:Japanese   Presentation type:Poster presentation  

KAKENHI (Grants-in-Aid for Scientific Research) 1

  1. 弱酸性腫瘍間質液のpH制御による抗癌剤治療効果の検討

    Grant number:21K20800  2021.8 - 2023.3

    日本学術振興会  科学研究費助成事業 研究活動スタート支援  研究活動スタート支援

    砂川 真輝

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    Authorship:Principal investigator 

    Grant amount:\3120000 ( Direct Cost: \2400000 、 Indirect Cost:\720000 )