Faculty Profiles - CHEN-YOSHIKAWA Toyofumi

Papers - CHEN-YOSHIKAWA Toyofumi

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Outcomes of various transplant procedures (single, sparing, inverted) in living-donor lobar lung transplantation Reviewed

Hiroshi Date, Akihiro Aoyama, Kyoko Hijiya, Hideki Motoyama, Tomohiro Handa, Hideyuki Kinoshita, Shiro Baba, Toshiyuki Mizota, Kenji Minakata, Toyofumi F. Chen-Yoshikawa

JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY Vol. 153 ( 2 ) page： 479 - 486 2017.2

Language：English Publishing type：Research paper (scientific journal) Publisher：MOSBY-ELSEVIER

Objectives: In standard living-donor lobar lung transplantation (LDLLT), the right and left lower lobes from 2 healthy donors are implanted. Because of the difficulty encountered in finding 2 donors with ideal size matching, various transplant procedures have been developed in our institution. The purpose of this retrospective study was to compare outcomes of nonstandard LDLLT with standard LDLLT.
Methods: Between June 2008 and January 2016, we performed 65 LDLLTs for critically ill patients. Functional size matching was performed by estimating graft forced vital capacity based on the donor's measured forced vital capacity and the number of pulmonary segments implanted. For anatomical size matching, 3dimensional computed tomography volumetry was performed. In cases of oversize mismatch, single-lobe transplant or downsizing transplant was performed. In cases of undersize mismatch, native upper lobe sparing transplant or rightleft inverted transplant was performed. In right-left inverted transplants, the donor's right lower lobe was inverted and implanted into the recipient's left chest cavity.
Results: Twenty-nine patients (44.6%) received nonstandard LDLLT, including 12 single-lobe transplants, 7 native upper lobe sparing transplants, 6 right-left inverted transplants, 2 sparing + inverted transplants, and 2 others. Thirty-six patients (57.4%) received standard LDLLT. Three-and five-year survival rates were similar between the 2 groups (89.1% and 76.6% after nonstandard LDLLT vs 78.0% and 71.1% after standard LDLLT, P = .712).
Conclusions: Various transplant procedures such as single, sparing and inverted transplants are valuable options when 2 donors with ideal size matching are not available for LDLLT.

DOI： 10.1016/j.jtcvs.2016.10.017

Web of Science

PubMed

Protective Effect of Inhaled Rho-Kinase Inhibitor on Lung Ischemia- Reperfusion Injury Reviewed

Keiji Ohata, Toyofumi F. Chen-Yoshikawa, Toshi Menju, Ei Miyamoto, Satona Tanaka, Mamoru Takahashi, Hideki Motoyama, Kyoko Hijiya, Akihiro Aoyama, Hiroshi Date

ANNALS OF THORACIC SURGERY Vol. 103 ( 2 ) page： 476 - 483 2017.2

Language：English Publishing type：Research paper (scientific journal) Publisher：ELSEVIER SCIENCE INC

Background. Rho-kinase, an intracellular serine/threonine kinase, is a key regulator of cytoskeletal dynamics. Recent studies have demonstrated that Rho-kinase is involved in the ischemia-reperfusion injury (IRI) pathogenesis of many organs; however, its involvement with lung IRI remains unclear. This study assessed the association of Rho-kinase with lung IRI and evaluated the protective effect of inhaled Rho-kinase inhibitors in lung IRI.
Methods. The study included isolated rat lung perfusion models, divided into three groups: sham, Rho-kinase inhibitor, and warm ischemia (n = 6 each). The lungs were exposed to 60 minutes of warm ischemia by perfusion cessation. At the onset of ischemia, nebulized fasudil, a novel Rho-kinase inhibitor, and saline were inhaled in the Rho-kinase inhibitor and warm ischemia groups, respectively. Perfusion was restarted after the ischemic period, and physiologic data were collected for 90 minutes. Lungs in the sham group were continuously perfused without ischemia or drug administrations. Protein expression in tissue specimens related to the Rho-kinase pathway was evaluated by Western blotting.
Results. Warm ischemia and subsequent reperfusion enhanced Rho-kinase activity, and this was suppressed by fasudil inhalation. Fasudil inhalation significantly attenuated IRI pathophysiology, including pulmonary vascular contraction, dynamic compliance, lung edema, and oxygenation. Molecular analysis showed that Rho-kinase suppressed myosin phosphatase and endothelial nitric oxide synthase activities, suggesting these are downstream targets of Rho-kinase during lung IRI pathogenesis.
Conclusions. The present study suggests that Rho-kinase activation is involved in lung IRI pathogenesis and that inhaled Rho-kinase inhibitors may attenuate this pathogenesis. (Ann Thorac Surg 2017; 103: 476-83) (C) 2017 by The Society of Thoracic Surgeons

DOI： 10.1016/j.athoracsur.2016.07.067

Web of Science

PubMed

Hypoxia-inducible factor 1 promotes chemoresistance of lung cancer by inducing carbonic anhydrase IX expression Reviewed

Terumasa Sowa, Toshi Menju, Toyofumi F. Chen-Yoshikawa, Koji Takahashi, Shigeto Nishikawa, Takao Nakanishi, Kei Shikuma, Hideki Motoyama, Kyoko Hijiya, Akihiro Aoyama, Toshihiko Sato, Makoto Sonobe, Hiroshi Harada, Hiroshi Date

CANCER MEDICINE Vol. 6 ( 1 ) page： 288 - 297 2017.1

Language：English Publishing type：Research paper (scientific journal) Publisher：WILEY-BLACKWELL

Lung cancer treatment is difficult owing to chemoresistance. Hypoxia-inducible factor 1 (HIF-1) and HIF-1-induced glycolysis are correlated with chemoresistance; however, this is not evident in lung cancer. We investigated the effect of HIF-1 and carbonic anhydrase IX (CAIX), a transmembrane protein neutralizing intracellular acidosis, on chemoresistance and prognosis of lung cancer patients after induction chemoradiotherapy. Associations of HIF-1, glucose transporter 1 (GLUT1), and CAIX with chemoresistance of lung cancer were investigated using A549 lung cancer cells under normoxia or hypoxia in vitro. HIF-1-induced reprogramming of glucose metabolic pathway in A549 cells and the effects of HIF-1 and CAIX on the cytotoxicity of vinorelbine were investigated. Immunohistochemical analyses were performed to determine HIF-1, GLUT1, and CAIX expression levels in cancer specimens from lung cancer patients after induction chemoradiotherapy. Hypoxia induced HIF-1 expression in A549 cells. Moreover, hypoxia induced GLUT1 and CAIX expression in A549 cells in a HIF-1-dependent manner. Glucose metabolic pathway was shifted from oxidative phosphorylation to glycolysis by inducing HIF-1 in A549 cells. HIF-1 and CAIX induced chemoresistance under hypoxia, and their inhibition restored the chemosensitivity of A549 cells. The expression levels of HIF-1, GLUT1, and CAIX were associated with poor overall survival of lung cancer patients after induction chemoradiotherapy. HIF-1 and CAIX affected the chemosensitivity of A549 cells and prognosis of lung cancer patients. Therefore, inhibition of HIF-1 and CAIX might improve prognosis of lung cancer patients after induction chemoradiotherapy. Further analysis might be helpful in developing therapies for lung cancer.

DOI： 10.1002/cam4.991

Web of Science

PubMed

Barr virus-associated post-transplantation lymphoproliferative disorder as acomplication after cadaveric lung transplantation following allogenic hematopoietic stem cell transplantation. Reviewed

Hoshino T, Chen-Yoshikawa TF, Nagasaka I, Hatsumi N, Takada S, Date H, Sakura T

Journal of Hematopoietic Cell Transplantation Vol. 6 ( 2 ) page： 120 - 124 2017

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