Early graft-infiltrating lymphocytes are not associated with graft rejection in a mouse model of skin transplantation.
Ryo Kanazawa; Ryoichi Goto; Takuya Harada; Takuji Ota; Nozomi Kobayashi; Kazuaki Shibuya; Yoshikazu Ganchiku; Masaaki Watanabe; Masaaki Zaitsu; Norio Kawamura; Tsuyoshi Shimamura; Akinobu Taketomi
Scandinavian journal of immunology, 30 Jul. 2024
Graft-infiltrating lymphocytes (GILs) play an important role in promoting rejection after organ transplantation. We recently reported that GILs that accumulated up to 3 days post-transplantation did not promote rejection, whereas GILs present 3-5 days post-transplantation promoted rejection in a mouse heart transplantation model. However, the immunological behaviour of GILs in murine skin transplantation remains unclear. GILs were isolated on days 3, 5 or 7 post-transplantation from C57BL/6 (B6) allogeneic skin grafts transplanted onto BALB/c mice. BALB/c Rag2-/- γc-/- mice (BRGs) underwent B6 skin graft transplantation 10 weeks after adoptive transfer of day 3, 5, or 7 GILs. BRGs reconstituted with day 5 or 7 GILs completely rejected B6 grafts. However, when B6 grafts harvested from recipient BALB/c mice on day 5 or 7 were re-transplanted into BRGs, half of the re-transplanted day 5 grafts established long-term survival, although all re-transplanted day 7 grafts were rejected. BRGs reconstituted with day 3 GILs did not reject B6 grafts. Consistently, re-transplantation using day 3 skin grafts resulted in no rejection. Administration of anti-CD25 antibodies did not prevent the phenomenon observed for the day 3 skin grafts. Furthermore, BRGs reconstituted with splenocytes from naïve BALB/c mice immediately rejected the naïve B6 skin grafts and the re-transplanted day 3 B6 grafts, suggesting that day 3 GILs were unable to induce allograft rejection during the rejection process. In conclusion, the immunological role of GILs depends on the time since transplantation. Day 3 GILs had neither protective nor alloreactive effects in the skin transplant model.

SGLT2 is upregulated to acquire cisplatin resistance and SGLT2 inhibition reduces cisplatin resistance in hepatoblastoma.
Sunao Fujiyoshi; Shohei Honda; Momoko Ara; Takafumi Kondo; Nozomi Kobayashi; Akinobu Taketomi
Journal of hepato-biliary-pancreatic sciences, Apr. 2024
BACKGROUND: Cancer cells can alter glucose metabolism and regulate the expression of glucose transporters. Hepatoblastoma patients undergo cisplatin-based chemotherapy; however, 22.3% of patients develop cisplatin resistance and thus face a poor prognosis. We hypothesized that glucose transporters are associated with acquiring cisplatin resistance with increasing sugar intake inhibiting glucose transporters could reduce cisplatin resistance in hepatoblastoma patients. METHODS: We established cisplatin-resistant HepG2 and HuH6 cells by continuous treatment with cisplatin. We evaluated the relationship between cisplatin resistance and glucose uptake. We used an expression array to select cisplatin-resistant associated glucose transporters and selected sodium-glucose cotransporter 2 (SGLT2). We used dapagliflozin as an SGLT2 inhibitor and evaluated glucose uptake and IC50 after dapagliflozin treatment in wild-type and resistant hepatoblastoma cells in vitro and in vivo. RESULTS: We found a strong relationship between cisplatin resistance and glucose uptake. Additionally, SGLT2 was upregulated in resistant cells after cisplatin treatment. After dapagliflozin treatment, glucose uptake and cisplatin resistance decreased in resistant cells. CONCLUSIONS: Cisplatin-resistant hepatoblastoma cells exhibited upregulated SGLT2 expression and activated glucose uptake to survive under cisplatin stress. SGLT2 inhibition decreased cellular resistance to cisplatin. SGLT2 inhibition with cisplatin therapy could be a novel therapeutic strategy for cisplatin-resistant hepatoblastoma patients.

Functional Roles of Graft Infiltrating Lymphocytes during Early Phase Post‐transplantation in Mouse Cardiac Transplantation Models
Yoshikazu Ganchiku; Ryoichi Goto; Ryo Kanazawa; Takuji Ota; Kazuaki Shibuya; Yasutomo Fukasaku; Nozomi Kobayashi; Rumi Igarashi; Norio Kawamura; Masaaki Zaitsu; Masaaki Watanabe; Akinobu Taketomi
Transplant International, 23 Oct. 2021

Early administration of amatuximab, a chimeric high-affinity anti-mesothelin monoclonal antibody, suppresses liver metastasis of mesothelin-expressing pancreatic cancer cells and enhances gemcitabine sensitivity in a xenograft mouse model.
Yuki Fujii; Hirofumi Kamachi; Fumihiko Matsuzawa; Tatsuzo Mizukami; Nozomi Kobayashi; Moto Fukai; Akinobu Taketomi
Investigational new drugs, Oct. 2021
Amatuximab is a promising therapeutic antibody targeting mesothelin, a 40-kDa glycoprotein that is highly expressed in pancreatic cancer. We investigated the effectiveness of early amatuximab treatment, imitating an adjuvant chemotherapy setting, and combination therapy with amatuximab and gemcitabine in liver metastasis of pancreatic cancer. Liver metastasis mouse models were established in 8-week-old male BALB/c nu/nu mice using the hemisplenic injection method. Tridaily amatuximab monotherapy or combination with gemcitabine was administered to the liver metastasis mouse model before metastatic lesions had formed huge masses. Gaussia luciferase-transfected AsPC-1 was used as a mesothelin-overexpressing pancreatic cancer cell line. The amount of liver metastases and the serum luciferase activity were significantly lower in the treatment groups than those in the control IgG group. Notably, the anti-tumor activity of gemcitabine was synergically enhanced by combination therapy with amatuximab. Furthermore, western blotting revealed that the high expression of phosphorylated c-Met and AKT in liver metastatic lesions treated with gemcitabine monotherapy was canceled by its combination with amatuximab. This result indicated that the observed synergic therapeutic effect may have occurred as a result of the inhibitory effect of amatuximab on the phosphorylation of c-Met and AKT, which were promoted by exposure to GEM. In conclusion, our study revealed that early administration of amatuximab alone or in combination with GEM significantly suppressed the liver metastases of mesothelin-expressing pancreatic cancer cells. A phase II clinical trial of amatuximab as part of an adjuvant chemotherapy regimen for resected pancreatic cancer is expected.

Mesothelin blockage by Amatuximab suppresses cell invasiveness, enhances gemcitabine sensitivity and regulates cancer cell stemness in mesothelin-positive pancreatic cancer cells.
Fumihiko Matsuzawa; Hirofumi Kamachi; Tatsuzo Mizukami; Takahiro Einama; Futoshi Kawamata; Yuki Fujii; Moto Fukai; Nozomi Kobayashi; Yutaka Hatanaka; Akinobu Taketomi
BMC cancer, 26 Feb. 2021
BACKGROUND: Mesothelin is a 40-kDa glycoprotein that is highly overexpressed in various types of cancers, however molecular mechanism of mesothelin has not been well-known. Amatuximab is a chimeric monoclonal IgG1/k antibody targeting mesothelin. We recently demonstrated that the combine therapy of Amatuximab and gemcitabine was effective for peritonitis of pancreatic cancer in mouse model. METHODS: We discover the role and potential mechanism of mesothelin blockage by Amatuximab in human pancreatic cells both expressing high or low level of mesothelin in vitro experiment and peritonitis mouse model of pancreatic cancer. RESULTS: Mesothelin blockage by Amatuximab lead to suppression of invasiveness and migration capacity in AsPC-1 and Capan-2 (high mesothelin expression) and reduce levels of pMET expression. The combination of Amatuximab and gemcitabine suppressed proliferation of AsPC-1 and Capan-2 more strongly than gemcitabine alone. These phenomena were not observed in Panc-1 and MIA Paca-2 (Mesothelin low expression). We previously demonstrated that Amatuximab reduced the peritoneal mass in mouse AsPC-1 peritonitis model and induced sherbet-like cancer cell aggregates, which were vanished by gemcitabine. In this study, we showed that the cancer stem cell related molecule such as ALDH1, CD44, c-MET, as well as proliferation related molecules, were suppressed in sherbet-like aggregates, but once sherbet-like aggregates attached to peritoneum, they expressed these molecules strongly without the morphological changes. CONCLUSIONS: Our work suggested that Amatuximab inhibits the adhesion of cancer cells to peritoneum and suppresses the stemness and viability of those, that lead to enhance the sensitivity for gemcitabine.

Role of Wnt5a in suppressing invasiveness of hepatocellular carcinoma via epithelial-mesenchymal transition.
Kazuki Wakizaka; Toshiya Kamiyama; Kenji Wakayama; Tatsuya Orimo; Shingo Shimada; Akihisa Nagatsu; Hirofumi Kamachi; Hideki Yokoo; Moto Fukai; Nozomi Kobayashi; Tomoko Mitsuhashi; Akinobu Taketomi
Oncology letters, Nov. 2020
Inappropriate activation of the canonical Wnt signaling pathway is associated with progression of hepatocellular carcinoma (HCC). However, the association between the non-canonical pathway activated by Wnt5a and HCC is not well known. The present study investigated the significance of Wnt5a expression in HCC. Immunohistochemical staining of Wnt5a was performed on specimens from 243 patients who underwent hepatic resection for HCC. The present study investigated whether Wnt5a expression was associated with clinical and pathological factors and prognosis. Wnt5a expression in human HCC cell lines was investigated using western blotting. The effects of overexpression or knockdown of Wnt5a were evaluated using proliferation and invasion assays. Changes in epithelial-mesenchymal transition (EMT)-related molecules were investigated using western blotting. Wnt5a negativity was significantly associated with poor tumor differentiation and positive vascular invasion. In univariate analysis, Wnt5a negativity was identified as a significant prognostic factor for overall survival (OS). Multivariate analysis of OS demonstrated that Wnt5a negativity was an independent prognostic factor. Wnt5a expression was lower in HLE and HLF cells than in HepG2 and Huh7 cells. Knockdown of Wnt5a by short hairpin RNA transfection increased the proliferation and invasiveness of Huh7 cells, and decreased the expression levels of E-cadherin. In HLF cells, overexpression of Wnt5a inhibited invasiveness and decreased the expression levels of vimentin. Wnt5a negativity was associated with poor tumor differentiation and positive vascular invasion, and was an independent poor prognostic factor in patients with HCC. Wnt5a may be a tumor suppressor involved in EMT-mediated changes in invasiveness.

Analysis of the correlation between alterations in N‑glycans and invasiveness in liver cancer cell lines
Hidenori Takahashi; Toshiya Kamiyama; Nozomi Hirane; Nozomi Kobayashi; Takeshi Aiyama; Akihisa Nagatsu; Shingo Shimada; Tatsuya Orimo; Tatsuhiko Kakisaka; Moto Fukai; Hideki Yokoo; Hirofumi Kamachi; Shin‑Ichiro Nishimura; Akinobu Taketomi
Oncology Reports, 08 Oct. 2020

早期ステージ大腸癌根治切除後の異時性肝転移に関わるリスク因子の探索　　　　　　　　　　　　　　　
沢田 尭史; 市川 伸樹; 吉田 雅; 小林 希; 本間 重紀; 武冨 紹信
日本癌学会総会記事, Oct. 2020

早期ステージ大腸癌根治切除後の異時性肝転移に関わるリスク因子の探索　　　　　　　　　　　　　　　
沢田 尭史; 市川 伸樹; 吉田 雅; 小林 希; 本間 重紀; 武冨 紹信
日本癌学会総会記事, Oct. 2020

肝細胞癌における癌関連線維芽細胞と癌細胞の相互作用の検討　　　　　　　　　　　　　　　
Aug. 2020

温阻血再灌流傷害における肝内脂質局在変化の視覚化 脂質分布と機能の基礎的解明と治療標的としての可能性　　　　　　　　　　　　　　　
Aug. 2020

Imaging Mass Spectrometry Reveals the Changes in the Taurine Conjugates of Dihydroxycholanoic Acid During Hepatic Warm Ischemia and Reperfusion in a Rat Model
Kengo Shibata; Takahiro Hayasaka; Satsuki Hashimoto; Kohei Umemoto; Takahisa Ishikawa; Sodai Sakamoto; Koichi Kato; Shingo Shimada; Norio Kawamura; Kenji Wakayama; Nozomi Kobayashi; Yuka Hama; Moto Fukai; Tsuyoshi Shimamura; Akinobu Taketomi
Transplantation Proceedings, 01 Jul. 2020

Prognostic impact of CD8+ T cell distribution and its association with the HLA class I expression in intrahepatic cholangiocarcinoma.
Yoh Asahi; Kanako C Hatanaka; Yutaka Hatanaka; Toshiya Kamiyama; Tatsuya Orimo; Shingo Shimada; Akihisa Nagatsu; Yuzuru Sakamoto; Hirofumi Kamachi; Nozomi Kobayashi; Moto Fukai; Akinobu Taketomi
Surgery today, 10 Feb. 2020, [Reviewed]
PURPOSE: A lack of effective systemic therapy is one reason for the poor prognosis of intrahepatic cholangiocarcinoma. Newly developed immune checkpoint inhibitors function by minimizing CD8+ T cell suppression to improve tumor-specific responses. This study aimed to examine the characteristics of CD8+ T cells in intrahepatic cholangiocarcinoma. METHODS: Clinicopathological data, including the overall survival, of 69 cases of postoperative intrahepatic cholangiocarcinoma were prospectively investigated. We then immunohistochemically stained for CD8, Foxp3, CD163, PD-L1, and human leukocyte antigen (HLA) class I and counted the number of CD8+ T cells, Foxp3+ T cells, and CD163+ macrophages in different areas (outer border, interborder, and intratumor). RESULTS: A significant difference was found in the 5-year overall survival between the CD8+ T cell high group (45.5%) and low group (24.7%) in the outer border area (p = 0.0103). Furthermore, the number of CD8+ T cells and the high expression of HLA class I were positively correlated (p = 0.0341). CONCLUSION: The number of CD8+ T cells in the outer border area of the tumor correlated with the HLA class I expression of intrahepatic cholangiocarcinoma and may therefore be a prognostic factor for patients with postoperative intrahepatic cholangiocarcinoma.

PREDICTION OF HEPATIC WARM ISCHEMIA AND REPERFUSION INJURY BY LYSOPHOSPHOLIPIDS - COMPREHENSIVE ANALYSIS BY IMAGING MASS SPECTROMETRY (IMS)
Shibata Kengo; Hayasaka Takahiro; Fukai Moto; Kato Koichi; Ishikawa Takahisa; Umemoto Kohei; Shimada Shingo; Kobayashi Nozomi; Shimamura Tsuyoshi; Kimura Taichi; Taketomi Akinobu
TRANSPLANT INTERNATIONAL, Oct. 2019, [Reviewed]

水素ガスの虚血・再灌流障害軽減効果と臨床応用の展望 虚血再灌流傷害に対する水素ガスの作用点の探索
Oct. 2019, [Reviewed]

Lipidomic Analysis in Liver Cancer Cells Regulated FABP5 Expression
Hayasaka Takahiro; Ohata Takanori; Yokoo Hideki; Kobayashi Nozomi; Kamiyama Toshiya; Taketomi Akinobu
CANCER SCIENCE, Dec. 2018, [Reviewed]

Post-reperfusion hydrogen gas treatment ameliorates ischemia reperfusion injury in rat livers from donors after cardiac death: a preliminary study.
Takahisa Ishikawa; Shingo Shimada; Moto Fukai; Taichi Kimura; Kouhei Umemoto; Kengo Shibata; Masato Fujiyoshi; Sunao Fujiyoshi; Takahiro Hayasaka; Norio Kawamura; Nozomi Kobayashi; Tsuyoshi Shimamura; Akinobu Taketomi
Surgery today, Dec. 2018, [Reviewed]

The anti-mesothelin monoclonal antibody amatuximab enhances the anti-tumor effect of gemcitabine against mesothelin-high expressing pancreatic cancer cells in a peritoneal metastasis mouse model.
Tatsuzo Mizukami; Hirofumi Kamachi; Yuki Fujii; Fumihiko Matsuzawa; Takahiro Einama; Futoshi Kawamata; Nozomi Kobayashi; Yutaka Hatanaka; Akinobu Taketomi
Oncotarget, 18 Sep. 2018, [Reviewed]
Pancreatic cancer often has a very poor prognosis, even after complete resection. The recurrence of hepatic and peritoneal metastases is an important prognostic factor; therefore, the development of improved adjuvant therapy is urgently required. Mesothelin is a cell surface glycoprotein whose expression is restricted to a variety of cancer types, including pancreatic cancer. This expression pattern makes mesothelin an attractive target for cancer therapy, and several agents targeting mesothelin are currently in clinical trials. Here, we used the chimerized high-affinity anti-mesothelin monoclonal antibody amatuximab to investigate its effect on peritoneal metastasis. We used the AsPC-1 pancreatic cancer cell line engineered to express Gaussia luciferase (Gluc), (AsPC-1-Gluc) for in vivo experiments. Results showed that while amatuximab was not directly cytotoxic on an AsPC-1-Gluc tumor cells in a peritoneal metastasis model, it prevented the formation of tumor growth. In combination therapy with gemcitabine, amatuximab exhibited synergistic killing. Our results suggest that blockade of mesothelin by amatuximab may be a useful strategy for preventing the peritoneal dissemination of pancreatic cancer under an adjuvant setting.

Fatty acid-binding protein 5 function in hepatocellular carcinoma through induction of epithelial-mesenchymal transition
Takanori Ohata; Hideki Yokoo; Toshiya Kamiyama; Moto Fukai; Takeshi Aiyama; Yutaka Hatanaka; Kanako Hatanaka; Kenji Wakayama; Tatsuya Orimo; Tatsuhiko Kakisaka; Nozomi Kobayashi; Yoshihiro Matsuno; Akinobu Taketomi
CANCER MEDICINE, May 2017, [Reviewed]

Novel anti-inflammatory agent 3-[ (dodecylthiocarbonyl)-methyl]-glutarimide ameliorates murine models of inflammatory bowel disease
Nobuki Ichikawa; Kenichiro Yamashita; Tohru Funakoshi; Shin Ichihara; Moto Fukai; Masaomi Ogura; Nozomi Kobayashi; Masaaki Zaitsu; Tadashi Yoshida; Susumu Shibasaki; Yasuyuki Koshizuka; Yusuke Tsunetoshi; Masanori Sato; Takahiro Einama; Michitaka Ozaki; Kazuo Umezawa; Tomomi Suzuki; Satoru Todo
INFLAMMATION RESEARCH, Mar. 2016, [Reviewed]

A proteasome inhibitor, bortezomib prevents pancreatic islet graft loss after transplantation
Hitoshi Ono; Yoh Asahi; Tadashi Yoshida; Yasuyuki Koshizuka; Masaaki Watanabe; Utano Tomaru; Nozomi Kobayashi; Shin Emoto; Moto Fukai; Tsuyoshi Shimamura; Akinobu Taketomi; Satoru Todo; Kenichiro Yamashita
XENOTRANSPLANTATION, Nov. 2015, [Reviewed]

A PROTEASOME INHIBITOR, BORTEZOMIB PREVENTS PANCREATIC ISLET GRAFT LOSS AFTER TRANSPLANTATION.
Hitoshi Ono; Yoh Asahi; Tadashi Yoshida; Yasuyuki Koshizuka; Masaaki Watanabe; Utano Tomaru; Nozomi Kobayashi; Shin Emoto; Moto Fukai; Tsuyoshi Shimamura; Akinobu Taketomi; Satoru Todo; Kenichiro Yamashita
TRANSPLANTATION, Nov. 2015, [Reviewed]

The Impact of c-Fos/Activator Protein-1 Inhibition on Allogeneic Pancreatic Islet Transplantation
T. Yoshida; K. Yamashita; M. Watanabe; Y. Koshizuka; D. Kuraya; M. Ogura; Y. Asahi; H. Ono; S. Emoto; T. Mizukami; N. Kobayashi; S. Shibasaki; U. Tomaru; H. Kamachi; M. Matsushita; S. Shiozawa; S. Hirono; S. Todo
AMERICAN JOURNAL OF TRANSPLANTATION, Oct. 2015, [Reviewed]

Hydrogen sulfide augments survival signals in warm ischemia and reperfusion of the mouse liver
Shingo Shimada; Moto Fukai; Kenji Wakayama; Takahisa Ishikawa; Nozomi Kobayashi; Taichi Kimura; Kenichiro Yamashita; Toshiya Kamiyama; Tsuyoshi Shimamura; Akinobu Taketomi; Satoru Todo
SURGERY TODAY, Jul. 2015, [Reviewed]

3-[ (Dodecylthiocarbonyl)Methyl]-Glutarimide Attenuates Graft Arterial Disease by Suppressing Alloimmune Responses and Vascular Smooth Muscle Cell Proliferation
Masaaki Zaitsu; Kenichiro Yamashita; Susumu Shibasaki; Yusuke Tsunetoshi; Moto Fukai; Masaomi Ogura; Tadashi Yoshida; Rumi Igarashi; Nozomi Kobayashi; Kazuo Umezawa; Satoru Todo
TRANSPLANTATION, May 2015, [Reviewed]

Successful penile reconstruction after multimodal therapy in patients with primitive neuroectodermal tumor originating from the penis
Tomoshige Akino; Nobuo Shinohara; Kanako Hatanaka; Nozomi Kobayashi; Yuhei Yamamoto; Katsuya Nonomura
INTERNATIONAL JOURNAL OF UROLOGY, Jun. 2014, [Reviewed]

A pilot study for cellular detection of circulating tumor cells and disseminated tumor cells of patients with hepatocellular carcinoma.
Nozomi Minagawa; Hideyasu Sakihama; Nozomi Kobayashi; Mito Obara; Susumu Shibasaki; Kenji Wakayama; Tatsuya Orimo; Tatsuhiko Kakisaka; Yousuke Tsuruga; Shigenori Homma; Hideki Yokoo; Hirofumi Kamachi; Hideki Kawamura; Norihiko Takahashi; Toshiya Kamiyama; Akinobu Taketomi
JOURNAL OF CLINICAL ONCOLOGY, May 2014, [Reviewed]

Comparison of circulating tumor cells (CTC) and disseminated tumor cells (DTC) in patients with colorectal carcinoma for a predictive marker for tumor recurrence.
Hideyasu Sakihama; Nozomi Kobayashi; Nozomi Minagawa; Tatsushi Shimokuni; Shigenori Homma; Norihiko Takahashi; Toshiya Kamiyama; Akinobu Taketomi
JOURNAL OF CLINICAL ONCOLOGY, May 2013, [Reviewed]

A pilot study for cellular detection of circulating tumor cells and disseminated tumor cells of patients with hepatocellular carcinoma.
Nozomi Minagawa; Hideyasu Sakihama; Nozomi Kobayashi; Kenji Wakayama; Tatsuhiko Kakisaka; Yousuke Tsuruga; Tatsushi Shimokuni; Shigenori Homma; Hideki Yokoo; Hirofumi Kamachi; Norihiko Takahashi; Toshiya Kamiyama; Akinobu Taketomi
JOURNAL OF CLINICAL ONCOLOGY, May 2013, [Reviewed]

Preoperative detection of circulating tumor cells in patients with colorectal carcinoma: Correlation with clinicopathologic variables and recurrence.
Hideyasu Sakihama; Nozomi Kobayashi; Tohru Funakoshi; Tatsushi Shimokuni; Shigenori Homma; Norihiko Takahashi; Akihiko Kataoka; Michitaka Ozaki; Toshiya Kamiyama; Akinobu Taketomi
JOURNAL OF CLINICAL ONCOLOGY, May 2012, [Reviewed]

Immunomodulatory Effect of Nuclear Factor-kappa B Inhibition by Dehydroxymethylepoxyquinomicin in Combination With Donor-Specific Blood Transfusion
Ryoichi Goto; Kenichiro Yamashita; Takeshi Aoyagi; Shinya Ueki; Motohiro Uno; Tetsu Oura; Nozomi Kobayashi; Rumi Igarashi; Susumu Shibasaki; Kenji Wakayama; Gentaro Hirokata; Tomohiro Shibata; Masaaki Zaitsu; Kazuo Umezawa; Michitaka Ozaki; Satoru Todo
TRANSPLANTATION, Apr. 2012, [Reviewed]

A novel NF-kappa B inhibitor, dehydroxymethylepoxyquinomicin, ameliorates inflammatory colonic injury in mice
Tohru Funakoshi; Kenichiro Yamashita; Nobuki Ichikawa; Moto Fukai; Tomomi Suzuki; Ryoichi Goto; Tetsu Oura; Nozomi Kobayashi; Takehiko Katsurada; Shin Ichihara; Michitaka Ozaki; Kazuo Umezawa; Satoru Todo
JOURNAL OF CROHNS & COLITIS, Mar. 2012, [Reviewed]

alpha-fetoprotein, vascular endothelial growth factor receptor-1 and early recurrence of hepatoma
Toshiya Kamiyama; Masato Takahashi; Kazuaki Nakanishi; Hideki Yokoo; Hirofumi Kamachi; Nozomi Kobayashi; Michitaka Ozaki; Satoru Todo
WORLD JOURNAL OF GASTROENTEROLOGY, Jan. 2012, [Reviewed]

DTCM-GLUTARIMIDE SUPPRESSES IFN-gamma AND AMELIORATES CARDIAC ALLOGRAFT ARTERIOSCLEROSIS IN MICE
Masaaki Zaitsu; Kenichiro Yamashita; Susumu Shibasaki; Yusuke Tsunetoshi; Masaomi Ogura; Tadashi Yoshida; Kenji Wakayama; Gentaro Hirokata; Rumi Igarashi; Nozomi Kobayashi; Michitaka Ozaki; Kazuo Umezawa; Satoru Todo
TRANSPLANT INTERNATIONAL, Sep. 2011, [Reviewed]

A Novel Anti-Inflammatory Agent, 3-[ (Dodecylthiocarbonyl)-Methyl]-Glutarimide, Ameliorates Murine Models of Inflammatory Bowel Disease
Nobuki Ichikawa; Kenichiro Yamashita; Tohru Funahashi; Shin Ichihara; Nozomi Kobayashi; Yasuyuki Koshizuka; Masaaki Zaitsu; Moto Fukai; Tomomi Suzuki; Michitaka Ozaki; Kazuo Umezawa; Satoru Todo
GASTROENTEROLOGY, May 2011, [Reviewed]

Array comparative genomic hybridization analysis revealed four genomic prognostic biomarkers for primary gastric cancers
Nobumoto Tomioka; Keiko Morita; Nozomi Kobayashi; Mitsuhiro Tada; Tomoo Itoh; Soichiro Saitoh; Masao Kondo; Norihiko Takahashi; Akihiko Kataoka; Kazuaki Nakanishi; Masato Takahashi; Toshiya Kamiyama; Michitaka Ozaki; Takashi Hirano; Satoru Todo
CANCER GENETICS AND CYTOGENETICS, Aug. 2010, [Reviewed]

A Novel NF-kappa B Inhibitor, DHMEQ, Ameliorates Inflammatory Colonic Injuries in Mice
Funakoshi Tohru; Yamashita Kenichiro; Ichikawa Nobuki; Fukai Moto; Suzuki Tomomi; Goto Ryoichi; Oura Tetsu; Kobayashi Nozomi; Katsurada Takehiko; Ozaki Michitaka; Umezawa Kazuo; Todo Satoru
GASTROENTEROLOGY, May 2010, [Reviewed]

Circulating tumor cellsの検出法
佐々木彩実; 崎浜秀康; 小林希; 高橋典彦; 松下通明; 藤堂省
日本アフェレシス学会雑誌, 31 May 2009

CXCL12/CXCR4抑制による転移抑制効果の検討 骨髄由来造血系前駆細胞とpermissive nicheの観点から
Feb. 2009

Right- and left-sided colorectal cancers display distinct expression profiles and the anatomical stratification allows a high accuracy prediction of lymph node metastasis
K Komuro; M Tada; E Tamoto; A Kawakami; A Matsunaga; K Teramoto; G Shindoh; M Takada; K Murakawa; M Kanai; N Kobayashi; Y Fujiwara; N Nishimura; J Hamada; A Ishizu; H Ikeda; S Kondo; H Katoh; T Moriuchi; T Yoshiki
JOURNAL OF SURGICAL RESEARCH, Apr. 2005, [Reviewed]

Prediction of lymphatic invasion/lymph node metastasis, recurrence, and survival in patients with gastric cancer by cDNA array-based expression profiling
K Teramoto; M Tada; E Tamoto; M Abe; A Kawakami; K Komuro; A Matsunaga; G Shindoh; M Takada; K Murakawa; M Kanai; N Kobayashi; Y Fujiwara; N Nishimura; K Shirata; T Takahishi; A Ishizu; H Ikeda; J Hamada; S Kondo; H Katoh; T Moriuchi; T Yoshiki
JOURNAL OF SURGICAL RESEARCH, Apr. 2005, [Reviewed]

Prediction of lymph node metastasis and perineural invasion of biliary tract cancer by selected features from cDNA array data
K Murakawa; M Tada; M Takada; E Tamoto; G Shindoh; K Teramoto; A Matsunaga; K Komuro; M Kanai; A Kawakami; Y Fujiwara; N Kobayashi; K Shirata; N Nishimura; S Okushiba; S Kondo; J Hamada; H Katoh; T Yoshiki; T Moriuchi
JOURNAL OF SURGICAL RESEARCH, Dec. 2004, [Reviewed]

Gene-expression profile changes correlated with tumor progression and lymph node metastasis in Esophageal cancer
E Tamoto; M Tada; K Murakawa; M Takada; G Shindo; K Teramoto; A Matsunaga; K Komuro; M Kanai; A Kawakami; Y Fujiwara; N Kobayashi; K Shirata; N Nishimura; SI Okushiba; S Kondo; J Hamada; T Yoshiki; T Moriuchi; H Katoh
CLINICAL CANCER RESEARCH, Jun. 2004, [Reviewed]

Search for risk factors related to liver metastasis after radical resection of early stage colorectal cancer
Akifumi Sawada; Nobuki Ichikawa; Tadashi Yoshida; Nozomi Kobayashi; Shigenori Homma; Akinobu Taketomi
CANCER SCIENCE, Feb. 2021

生存シグナル増強を目指した機械灌流による肝グラフトの薬剤性コンディショニング法の探索
2019

次世代の臓器保存法 温虚血肝グラフトの傷害予測マーカーの探索 虚血再灌流時のリゾリン脂質の役割　　　　　　　　　　　　　　　
柴田 賢吾; 深井 原; 島田 慎吾; 石川 隆壽; 若山 顕治; 藤好 直; 小林 希; 加藤 紘一; 早坂 孝宏; 三野 和宏; 川村 典生; 嶋村 剛; 武冨 紹信
Organ Biology, Oct. 2018
(一社)日本臓器保存生物医学会

FABP5発現調節した肝癌細胞株のリピドミクス解析(Lipidomic Analysis in Liver Cancer Cells Regulated FABP5 Expression)　　　　　　　　　　　　　　　
早坂 孝宏; 大畑 多嘉宣; 横尾 英樹; 小林 希; 神山 俊哉; 武冨 紹信
日本癌学会総会記事, Sep. 2018
日本癌学会

FABP5発現調節した肝癌細胞株のリピドミクス解析(Lipidomic Analysis in Liver Cancer Cells Regulated FABP5 Expression)　　　　　　　　　　　　　　　
早坂 孝宏; 大畑 多嘉宣; 横尾 英樹; 小林 希; 神山 俊哉; 武冨 紹信
日本癌学会総会記事, Sep. 2018
日本癌学会

脂肪肝,虚血再灌流障害をターゲットとしたAMPKの役割
島田慎吾; 柴田賢吾; 小林希; 三好早香; 早坂孝宏; 深井原; 嶋村剛; 武冨紹信
Organ Biology, 15 Jul. 2018
AMPK(AMP-activated protein kinase)はエネルギー代謝における主要な調節分子であるが、近年では、脂質代謝における重要な制御分子であることや虚血再灌流障害における抗酸化、抗炎症、抗アポトーシス、オートファジー調節作用に加えて、腫瘍細胞の増殖抑制作用も報告されている。多様な働きを有するAMPKについて、主に脂肪代謝、虚血再灌流障害、腫瘍との関連を中心に概説した。, (一社)日本臓器保存生物医学会

脂肪肝、虚血再灌流障害をターゲットとしたAMPKの役割　　　　　　　　　　　　　　　
島田 慎吾; 柴田 賢吾; 小林 希; 三好 早香; 早坂 孝宏; 深井 原; 嶋村 剛; 武冨 紹信
Organ Biology, Jul. 2018
AMPK(AMP-activated protein kinase)はエネルギー代謝における主要な調節分子であるが、近年では、脂質代謝における重要な制御分子であることや虚血再灌流障害における抗酸化、抗炎症、抗アポトーシス、オートファジー調節作用に加えて、腫瘍細胞の増殖抑制作用も報告されている。多様な働きを有するAMPKについて、主に脂肪代謝、虚血再灌流障害、腫瘍との関連を中心に概説した。, (一社)日本臓器保存生物医学会

シスプラチン耐性肝芽腫細胞株に高発現したトランスポーター遺伝子
藤好直; 本多昌平; 湊雅嗣; 荒桃子; 宮城久之; 小林希; 武冨紹信
がんと代謝研究会プログラム&抄録集, May 2018

心停止ドナー肝のNrf2と生存シグナルを増強させる薬剤性コンディショニング法の探索
深井原; 島田慎吾; 小林希; 中藪拓哉; 石川隆壽; 柴田賢吾; 梅本浩平; 鈴木崇史; 三野和宏; 嶋村剛; 武冨紹信
日本外科学会定期学術集会(Web), Apr. 2018
(一社)日本外科学会

臓器灌流時のコンディショニング法の探索
深井原; 小林希; 島田慎吾; 梅本浩平; 中薮拓哉; 柴田賢吾; 早坂孝宏; 鈴木崇史; 大谷晋太郎; 橋本咲月; 三野和宏; 嶋村剛; 武冨紹信; 武冨紹信; 武冨紹信
Organ Biology, 10 Nov. 2017

Ex vivo灌流によるAMPK活性化を介した脂肪肝グラフトに対するコンディショニング法の開発
島田慎吾; 柴田賢吾; 中薮拓哉; 梅本浩平; 小林希; 藤好直; 三好早香; 早坂孝宏; 石川隆壽; 深井原; 嶋村剛; 武冨紹信
Organ Biology, 10 Nov. 2017

小腸上皮細胞の低温保存における溶存酸素と酸化ストレスの影響
中薮拓哉; 深井原; 島田慎吾; 小林希; 梅本浩平; 柴田賢吾; 早坂孝宏; 鈴木崇史; 大谷晋太郎; 橋本咲月; 三野和宏; 嶋村剛; 武冨紹信; 武冨紹信
Organ Biology, 10 Nov. 2017

What is the necessary technique for the development of organ perfusion?
Fukai Moto; Shimada Shingo; Umemoto Kouhei; Nakayabu Takuya; Kobayashi Nozomi; Mino Kazuhiro; Shimamura Tsuyoshi; Taketomi Akinobu
Organ Biology, 2017
Extensive efforts to repair the extended criteria donor (ECD) grafts by machine perfusion has been reported. Although the optimal conditions, such as the perfusate, temperature, time, and the device, has not yet been established, organ perfusion is generally accepted as a promising concept. Here, we review current progress of antioxidant and anti-inflammatory treatment by induction of protective transcription factors (TFs), Nrf2 in relation to the other TFs (AP-1 and NF-kB). These TFs are mainly regulated by the redox status of intracellular thiols. Possible interactions of the TFs and the methods to regulate their activity have been described., The Japan Society for Organ Preservation and Biology

臓器灌流法の先にあるべき技術の開発
深井原; 島田慎吾; 小林希; 梅本浩平; 大谷晋太郎; 中薮拓哉; 三野和宏; 山下健一郎; 嶋村剛; 武冨紹信
Organ Biology, 20 Oct. 2016

14-3-3ζ-Mediated Stimulation of Oxidative Phosphorylation Exacerbates Oxidative Damage under Hypothermic Oxygenated Conditions in Human Renal Tubular Cells (HK-2)
M. Fukai; N. Kobayashi; T. Ishikawa; K. Wakayama; S. Shimada; K. Umemoto; S. Ohtani; M. Fujiyoshi; K. Yamashita; T. Shimamura; A. Taketomi
Transplantation Proceedings, 01 May 2016

低温酸素化状態における14‐3‐3zetaによるエネルギー産生と細胞内シグナルの制御―ヒト尿細管上皮細胞株(HK2)を用いた検討
深井原; 小林希; 石川隆壽; 梅本浩平; 島田慎吾; 若山顕治; 大谷晋太郎; 橋本咲月; 藤好真人; 山下健一郎; 嶋村剛; 武冨紹信
日本外科学会定期学術集会(Web), 2016

Significance of regulating protein functions under hypothermic oxygenated conditions
Fukai Moto; Shimada Shingo; Kobayashi Nozomi; Ishikawa Takahisa; Umemoto Kohei; Ohtani Shintaro; Yamashita Kenichiro; Shimamura Tsuyoshi; Taketomi Akinobu
Organ Biology, 2016
Cellular survival and death during cold storage and hypothermic perfusion are regulated by intracellular signal, however, precise mechanisms remain elusive. Although the effector proteins of cellular fate work actually during 6 to 24 hours after rewarming and reoxygenation, the triggering events have already been regulated during organ procurement, transportation, and implantation before reperfusion. In this review, we summarize some potential mechanisms of regulating intracellular signals, mainly focused on the energy production and post-translational regulation under hypothermic conditions.<br>A chaperon protein, 14-3-3&zeta;, regulates over 200 of the protein activity by covering the phosphorylation site within a 14-3-3 binding motif. Sirtuins also regulates many proteins directly and indirectly relates to the cell survival and death under some difficult conditions including cold and/or hypoxic insults. Sirtuins regulate many mitochondrial proteins primarily by deacetylation instead of ATP consuming processes. Further, sirtuins and 14-3-3s interact each other and sharing some target proteins, especially relating energy production and mitochondrial functions. Although these facts have been reported in ectotherms, hibernators, to human, little is known about its role in organ preservation, perfusion, and transplantation. Here, we reviewed its potential significance for the future research in the field of organ repair., The Japan Society for Organ Preservation and Biology

低温灌流時の酸化的リン酸化と細胞内シグナルの制御~尿細管上皮を用いた検討
深井原; 石川隆壽; 島田慎吾; 梅本浩平; 大谷晋太郎; 小林希; 山下健一郎; 嶋村剛; 武冨紹信
Organ Biol, 20 Oct. 2015

OCIAD2はDNAメチル化により制御される肝芽腫の新規癌抑制遺伝子である
湊雅嗣; 本多昌平; 小林希; 三好早香; 鈴木拓; 岡田忠雄; 宮城久之; 檜山英三; 武冨紹信
日本小児外科学会雑誌, 25 May 2015

YIA-2-4 PARP6の高メチル化は肝芽腫の新しい予後因子である(YIA-2 若手優秀演題賞(2)「その他」,第114回日本外科学会定期学術集会)
05 Mar. 2014

PS-157-7 肝細胞癌における循環腫瘍細胞ならびに骨髄腫瘍細胞と臨床病理組織学的因子の検討(PS-157 肝 肝細胞癌-4,ポスターセッション,第114回日本外科学会定期学術集会)
05 Mar. 2014

PARP6の高メチル化は肝芽腫の新しい予後因子である
湊雅嗣; 本多昌平; 岡田忠雄; 三好早香; 小林希; 檜山英三; 武冨紹信
日本外科学会雑誌, 05 Mar. 2014

肝細胞癌における循環腫瘍細胞ならびに骨髄腫瘍細胞と臨床病理組織学的因子の検討
皆川のぞみ; 崎浜秀康; 小林希; 小原美都; 柴崎晋; 若山顕治; 折茂達也; 柿坂達彦; 敦賀陽介; 本間重紀; 横尾秀樹; 蒲池浩文; 川村秀樹; 高橋典彦; 神山俊哉; 武冨紹信
日本外科学会雑誌, 05 Mar. 2014

肝細胞癌における循環腫瘍細胞ならびに骨髄腫瘍細胞と臨床病理組織学的因子の関連性(Cellular detection of circulating tumor cells and disseminated tumor cells of patients with hepatocellular carcinoma)　　　　　　　　　　　　　　　
皆川 のぞみ; 崎浜 秀康; 小林 希; 若山 顕治; 折茂 達也; 柿坂 達彦; 敦賀 陽介; 本間 重紀; 横尾 秀樹; 蒲池 浩文; 高橋 典彦; 神山 俊哉; 武冨 紹信
日本癌学会総会記事, Oct. 2013
日本癌学会

大腸癌の骨髄腫瘍細胞はCD133を発現しているか?　　　　　　　　　　　　　　　
崎浜 秀康; 小林 希; 皆川 のぞみ; 下國 達志; 本間 重紀; 高橋 典彦; 神山 俊哉; 武冨 紹信
日本消化器外科学会総会, Jul. 2013
(一社)日本消化器外科学会

大腸癌の循環腫瘍細胞と骨髄腫瘍細胞は再発予測マーカーとなりうるか?　　　　　　　　　　　　　　　
皆川 のぞみ; 崎浜 秀康; 小林 希; 下國 達志; 本間 重紀; 高橋 典彦; 神山 俊哉; 武冨 紹信
日本大腸肛門病学会雑誌, Jun. 2013
(一社)日本大腸肛門病学会

WS-17-3 大腸癌における血申遊離癌細胞と骨髄癌細胞 : 再発予測因子としての比較検討(WS ワークショップ,第113回日本外科学会定期学術集会)
05 Mar. 2013

PS-093-3 肝細胞癌における血中遊離癌細胞と骨髄癌細胞の同定の試み(PS ポスターセッション,第113回日本外科学会定期学術集会)
05 Mar. 2013

大腸癌における血中遊離癌細胞と骨髄癌細胞~再発予測因子としての比較検討~
崎浜秀康; 小林希; 皆川のぞみ; 下國達志; 本間重紀; 高橋典彦; 神山俊哉; 武冨紹信
日本外科学会雑誌, 05 Mar. 2013

肝細胞癌における血中遊離癌細胞と骨髄癌細胞の同定の試み
皆川のぞみ; 崎浜秀康; 小林希; 若山顕治; 柿坂達彦; 敦賀陽介; 下國達志; 本間重紀; 横尾秀樹; 蒲池浩文; 高橋典彦; 神山俊哉; 武冨紹信
日本外科学会雑誌, 05 Mar. 2013

大腸癌の循環腫瘍細胞と骨髄腫瘍細胞は再発予測マーカーとなりうるか?
皆川のぞみ; 崎浜秀康; 小林希; 下國達志; 本間重紀; 高橋典彦; 神山俊哉; 武冨紹信
大腸癌研究会プログラム・抄録集, 2013

肝細胞癌における循環腫瘍細胞ならびに骨髄腫瘍細胞と臨床病理組織学的因子の検討
皆川のぞみ; 崎浜秀康; 小林希; 小原美都; 柴崎晋; 若山顕治; 柿坂達彦; 敦賀陽介; 本間重紀; 横尾秀樹; 蒲池浩文; 川村秀樹; 高橋典彦; 神山俊哉; 武冨紹信
日本消化器癌発生学会総会プログラム・抄録集, 2013

肝細胞癌における骨髄転移性腫瘍の同定(Cellular detection of disseminated tumor cells in bone marrow of patients with hepatocellular carcinoma)　　　　　　　　　　　　　　　
崎浜 秀康; 小林 希; 皆川 のぞみ; 柿坂 達彦; 敦賀 陽介; 下國 達志; 本間 重紀; 横尾 英樹; 蒲池 浩文; 中西 一彰; 高橋 典彦; 神山 俊哉; 武冨 紹信
日本癌学会総会記事, Aug. 2012
日本癌学会

臨床応用に向かう消化器外科領域基礎研究(消化管B) 大腸癌の循環腫瘍細胞と骨髄腫瘍細胞は再発予測マーカーとなりうるか? 術前血清CEA値との比較　　　　　　　　　　　　　　　
崎浜 秀康; 小林 希; 藤好 真人; 舩越 徹; 下國 達志; 本間 重紀; 高橋 典彦; 片岡 昭彦; 武冨 昭信
日本消化器外科学会総会, Jul. 2012
(一社)日本消化器外科学会

SF-089-5 大腸癌の骨髄微小転移同定のpilot study : 病理組織学的因子との関係(SF-089 サージカルフォーラム(89)大腸 基礎-2(浸潤・転移),第112回日本外科学会定期学術集会)
05 Mar. 2012

消化器癌に対する分子生物学の臨床応用(下部消化管) 大腸癌の循環腫瘍細胞同定を規定する因子　　　　　　　　　　　　　　　
崎浜 秀康; 小林 希; 藤好 真人; 下國 達志; 本間 重紀; 高橋 典彦; 片岡 昭彦; 尾崎 倫孝; 藤堂 省
日本消化器外科学会総会, Jul. 2011
(一社)日本消化器外科学会

SF-002-5 新規化合物DTCM-Gを用いたマウス慢性拒絶反応抑制効果の検討(SF-002 サージカルフォーラム(2)移植-1,第111回日本外科学会定期学術集会)
25 May 2011

PS-019-3 炎症性腸疾患モデルにおける新規化合物DTCM-Gの腸炎抑制効果に関する検討(PS-019 ポスターセッション(19)大腸:良性-4,第111回日本外科学会定期学術集会)
25 May 2011

新規化合物DTCM‐Gを用いたマウス慢性拒絶反応抑制効果の検討
財津雅昭; 山下健一郎; 柴崎晋; 常俊雄介; 若山顕治; 廣方玄太郎; 五十嵐留美; 小林希; 尾崎倫孝; 梅澤一夫; 藤堂省
移植, Oct. 2010

MACS(Magnet cell sorting system)を用いた大腸癌患者の循環腫瘍細胞の同定(Detection of circulating tumor cells in colorectal cancer patients by magnet cell sorting system)　　　　　　　　　　　　　　　
崎浜 秀康; 小林 希; 佐々木 彩実; 本間 重紀; 高橋 典彦; 片岡 昭彦; 尾崎 倫孝; 藤堂 省
日本癌学会総会記事, Aug. 2010
日本癌学会

OP-090-1 新規NF-kB阻害剤DHMEQの大腸炎モデルにおける炎症抑制作用(小腸基礎-2,一般口演,第110回日本外科学会定期学術集会)
05 Mar. 2010

OP-018-4 Magnet cell sorting(MACS) systemを用いた大腸癌の血中腫瘍細胞の同定(腫瘍マーカー-1,一般口演,第110回日本外科学会定期学術集会)
05 Mar. 2010

新規肝芽腫モデル細胞を活用したエピゲノム異常がもたらす腫瘍増悪性化機序の解明
01 Apr. 2025 - 31 Mar. 2028

The molecular mechanism of adenomatous polyposis coli-binding protein EB1 in HCC
Grant-in-Aid for Scientific Research (C)
Hokkaido University
01 Apr. 2013 - 31 Mar. 2016
We previously reported that adenomatous polyposis coli-binding protein EB1 (EB1) is overexpressed in HCC tissues by proteomics. In present study, ①EB1 expression significantly correlated with the degree of histological differentiation, AFP, vascular invasion status in HCC patients. Moreover, overall survival and recurrence rate was significantly poor in EB1-high expressed HCC patients. ②EB1 promoted cell proliferation, migration, invasion, tumor growth in HCC cell lines. ③Microarray analysis revealed that EB1 might regulate the expression level of Dlk-1. As a conclusion, EB1 may become a new biomarker of HCC and a potential molecular target of HCC therapy.