Faculty Profiles - CHEN-YOSHIKAWA Toyofumi

Papers - CHEN-YOSHIKAWA Toyofumi

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岡地祥太郎, 伊藤貴康, 若原恵子, 橋本直純, 中村彰太, 芳川豊史

気管支学 Vol. 44 ( 5 ) page： 400 - 400 2022.9

Relationship of smoking cessation period with the incidence of complications in lung cancer surgery Reviewed

Kadomatsu Y., Sugiyama T., Sato K., Nakanishi K., Ueno H., Goto M., Ozeki N., Nakamura S., Fukumoto K., Chen-Yoshikawa T.F.

European journal of cardio-thoracic surgery Vol. 62 ( 3 ) 2022.8

Authorship：Last author Language：English Publisher：European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery

OBJECTIVES: The incidence of postoperative complications is relatively high in smokers. Although 4-week smoking cessation before surgery is generally recommended, it has not been sufficiently studied in lung cancer surgery. This study investigated whether smoking cessation for a short period of time significantly reduced complications after lung cancer surgery. METHODS: This was a retrospective, observational study that investigated the relationship between the smoking cessation period and the incidence of complications in lung cancer surgery. Patients who underwent curative-intent surgery for lung cancer at our institution between January 2014 and December 2017 were included. The smokers were classified into the following 4 categories of smoking cessation period before surgery: current (<4 weeks), recent (4 weeks to 12 months), distant (12 months to 5 years) and ex-smokers (>5 years). RESULTS: A total of 911 patients were included in this study. The incidence of pulmonary complications was 5 times higher in the smoker group than in the never smoker group (12.9% vs 2.5%, P < 0.001). On multivariable analysis in both models, the odds ratio for complications was significantly higher in distant smokers than in recent smokers and never smokers. Across all models, low lung function significantly predicted the development of postoperative complications. CONCLUSIONS: The evidence-based smoking cessation duration that reduces the incidence of complications after thoracic surgery remains unclear. The incidence of postoperative complications was more strongly affected by low pulmonary function than by the duration of preoperative smoking cessation. For patients with marginal indications for surgery, postponing surgery to accommodate a smoking cessation period seemed unnecessary.

DOI： 10.1093/ejcts/ezac163

Scopus

Postoperative empyema complicated with descending necrotizing fasciitis: a case report. Reviewed International journal

Yuka Kadomatsu, Harushi Ueno, Masaki Goto, Naoki Ozeki, Shota Nakamura, Toyofumi Fengshi Chen-Yoshikawa

Surgical case reports Vol. 8 ( 1 ) page： 133 - 133 2022.7

Authorship：Last author Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: Empyema is a serious complication of lung surgery. CASE PRESENTATION: We report a case of Streptococcus anginosus empyema complicated by descending necrotizing fasciitis after surgery. Ten days after the initial surgery, the patient presented with arrhythmia and hypotension with septic shock. Pleural fluid analysis led to the diagnosis of empyema, and surgical debridement (second surgery) was performed. One week after the emergency surgery, a palpable pink erythematous skin change was observed on the ipsilateral iliac crest. Hence, the second emergency surgery (third surgery) was performed to debride the subcutaneous and intramuscular abscesses. CONCLUSIONS: The possibility of descending abscess and necrotizing fasciitis should be considered when Streptococcus anginosus is detected.

DOI： 10.1186/s40792-022-01492-9

PubMed

Impact of inspiratory muscle strength on exercise capacity after lung transplantation Reviewed

Sato T., Sato S., Oshima Y., Yoshioka Y., Hamada R., Nankaku M., Ikeda M., Nakajima D., Chen-Yoshikawa T.F., Date H., Matsuda S., Tabira K.

Physiotherapy Research International Vol. 27 ( 3 ) 2022.7

Language：English Publisher：Physiotherapy Research International

Background and Purpose: Though inspiratory muscle strength is essential for patients with respiratory disease, it is unclear whether the recovery of inspiratory muscle strength contributes to an exemplary achievement of exercise tolerance after lung transplantation (LTx). We aimed to elucidate the inspiratory muscle strength affects the recovery of exercise capacity after LTx. Methods: Recipients who underwent LTx between June 2017 and September 2018 were enrolled, and 6-min walking distance (6MWD), quadriceps force, inspiratory muscle strength (maximal inspiratory pressure [MIP]), and spirometry were evaluated at 3, 6, and 12 months after LTx. The relationships between inspiratory muscle strength and changes in physical performance were analyzed. Results: Nineteen recipients (mean age: 44.8 years, male: 32%) who completed all follow-ups were analyzed. At 3 months after LTx, mean MIP (88.4% predicted) and vital capacity (60.9% predicted), quadriceps force (QF; 2.1 N*m/kg), and 6MWD (504 m) were lower than normal values. After LTx, 6MWD significantly improved up to 12 months. From 3 to 6 months after LTx, changes in MIP were significantly associated with increases in 6MWD by univariate (r = 0.55, p = 0.02) and multivariate (β = 0.59, p = 0.01) regression analyses, whereas changes of QF in place of MIP were significantly associated with the recoveries of 6MWD from 6 to 12 months. Discussion: Improvements in MIP may impact the recovery of exercise capacity in the early phase after LTx. Factors that determine the improvement in exercise capacity following LTx may vary with postoperative time.

DOI： 10.1002/pri.1951

Scopus

Meflin-positive cancer-associated fibroblasts enhance tumor response to immune checkpoint blockade Reviewed

Miyai Y., Sugiyama D., Hase T., Asai N., Taki T., Nishida K., Fukui T., Chen-Yoshikawa T.F., Kobayashi H., Mii S., Shiraki Y., Hasegawa Y., Nishikawa H., Ando Y., Takahashi M., Enomoto A.

Life science alliance Vol. 5 ( 6 ) 2022.6

Language：English Publisher：Life science alliance

Cancer-associated fibroblasts (CAFs) are an integral component of the tumor microenvironment (TME). Most CAFs shape the TME toward an immunosuppressive milieu and attenuate the efficacy of immune checkpoint blockade (ICB) therapy. However, the detailed mechanism of how heterogeneous CAFs regulate tumor response to ICB therapy has not been defined. Here, we show that a recently defined CAF subset characterized by the expression of Meflin, a glycosylphosphatidylinositol-anchored protein marker of mesenchymal stromal/stem cells, is associated with survival and favorable therapeutic response to ICB monotherapy in patients with non-small cell lung cancer (NSCLC). The prevalence of Meflin-positive CAFs was positively correlated with CD4-positive T-cell infiltration and vascularization within non-small cell lung cancer tumors. Meflin deficiency and CAF-specific Meflin overexpression resulted in defective and enhanced ICB therapy responses in syngeneic tumors in mice, respectively. These findings suggest the presence of a CAF subset that promotes ICB therapy efficacy, which adds to our understanding of CAF functions and heterogeneity.

DOI： 10.26508/lsa.202101230

Scopus

『今日の治療薬2022-解説と便覧』

芳川豊史

胸部外科 Vol. 75 ( 6 ) page： 436 - 436 2022.6

Commentary: Less is more in thoracic surgery Invited Reviewed

Okado S., Chen-Yoshikawa T.F.

JTCVS Techniques Vol. 13 page： 242 - 243 2022.6

Impact of COVID-19 on living donor liver and kidney transplantation programs in Japan in 2020 Reviewed

Kuramitsu K., Yamanaga S., Osawa R., Hibi T., Yoshikawa M., Toyoda M., Shimata K., Yosuke E., Ono M., Kenmochi T., Sogawa H., Natori Y., Yano H., Chen-Yoshikawa T., Yoshida K., Fukumoto T., Yuzawa K., Egawa H.

Transplant Infectious Disease Vol. 24 ( 3 ) 2022.6

Language：English Publisher：Transplant Infectious Disease

Background: Although many transplant programs have been forced to suspend living donor transplants due to the emergence of coronavirus disease (COVID-19), there are relatively few real-time databases to assess center-level transplant activities. We aimed to delineate the actual impact of COVID-19 on living donor transplant programs and the resumption process in Japan. Methods: In a nationwide survey, questionnaires were sent to 32 liver transplant programs that had performed at least more than one case of living donor liver transplantation in 2019 and 132 kidney transplant programs that had performed more than one living donor kidney transplantation in 2018. Results: Thirty-one (96.9%) and 125 (94.7%) liver and kidney transplant programs responded, respectively. In the early pandemic period, 67.7% (21/31) of liver programs and 29.8% (37/125) of kidney programs were able to maintain transplant activities similar to those during the pre-pandemic period. After temporal suspension, 58.1% of kidney programs resumed their transplant activity after the number of local COVID-19 cases peaked. Establishing institutional COVID-19 screening, triage, and therapeutic management protocols was mandatory to resume transplant activity for 64.5% and 67.7% of liver and kidney programs, respectively. In the future wave of COVID-19, 67.7% of liver programs would be affected by institutional COVID-19 intensive care unit-bound patient numbers, and 55.7% of kidney programs would stop if hospital-acquired severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection spreads. Conclusions: This nationwide survey revealed for the first time how living donor liver and kidney: transplant programs changed in response to the COVID-19 pandemic in a country where living donor transplantations are predominant.

DOI： 10.1111/tid.13845

Scopus

Creation of a video library for education and virtual simulation of anatomical lung resection Reviewed

Tokuno J., Chen-Yoshikawa T.F., Nakao M., Iwakura M., Motoki T., Matsuda T., Date H.

Interactive Cardiovascular and Thoracic Surgery Vol. 34 ( 5 ) page： 808 - 813 2022.5

Authorship：Last author,　Corresponding author Language：English Publisher：Interactive Cardiovascular and Thoracic Surgery

OBJECTIVES: Recently, preoperative and intraoperative simulation using three-dimensional computed tomography (CT) has attracted much attention in thoracic surgery. However, because conventional three-dimensional CT only shows static images, dynamic simulation is required for a more precise operation. We previously reported on a resection process map for pulmonary resection, which we developed to generate virtual dynamic images from preoperative patient-specific CT scans. The goal of this study was to evaluate the feasibility of the clinical use of the resection process map for anatomical lung resection. METHODS: This study included 5 lobectomies for different lobes and 4 representative segmentectomies. Dissection of the pulmonary arteries, veins and bronchi were considered key parts of each procedure. To assess the description of images obtained from the resection process map, relevant clips from the actual surgical videos were collected, retrospectively replicated and superimposed on the resection process map to explain the procedures. RESULTS: In all surgical procedures, the resection process map successfully and semiautomatically generated a virtual dynamic image from the patient-specific CT data. Moreover, superimposition of the virtual images on the selected clips from the surgical videos showed no major differences. CONCLUSIONS: The resection process map could generate virtual images that corresponded to the actual surgical videos and has the potential for clinical use as preoperative and intraoperative simulation.

DOI： 10.1093/icvts/ivab379

Scopus

Image Guidance in Thoracic Surgery: Current Status and Future Outlook

Chen-Yoshikawa T. F.

Nihon Kikan Shokudoka Gakkai Kaiho Vol. 73 ( 2 ) page： 112 - 113 2022.4

Risk Assessment for Loss-of-Exercise Capacity After Lung Cancer Surgery: Current Advances in Surgery and Systemic Treatment Reviewed

Ozeki N., Kadomatsu Y., Mizuno Y., Inoue T., Nagaya M., Goto M., Nakamura S., Fukumoto K., Chen-Yoshikawa T.F.

World Journal of Surgery Vol. 46 ( 4 ) page： 933 - 941 2022.4

Authorship：Last author Language：English Publisher：World Journal of Surgery

Background: Considering advances in current post-recurrence treatment, we examined the prognostic significance of the number of risk factors for loss-of-exercise capacity (LEC) after lung cancer surgery, which were identified by our previous prospective observational study. Methods: Risk factors for LEC were defined as a short baseline 6-min walk distance (<400 m), older age (≥75 years), and low predicted postoperative diffusing capacity for carbon monoxide (<60%). Patients were classified as Risk 0/I/II/III according to the number of risk factors. The survival data were retrospectively analyzed. Results: Between 2014 and 2017, 564 patients (n = 307, 193, 57, 7; Risk 0/I/II/III) who underwent lung cancer surgery were included in the study. The number of risk factors was associated with smoking status, predicted postoperative forced expiratory volume in 1 s, histology, pathological stage, and adjuvant therapy. In a multivariate Cox regression analysis, compared to Risk 0, Risk I/II/III showed significant associations with overall survival (hazard ratios: 1.92, 3.35, 9.21; 95% confidence interval: 1.27–2.92, 2.01–5.58, 3.64–23.35; Risk I/II/III, respectively). In 141 patients with recurrence, molecular targeted therapies (MTTs) or immune checkpoint inhibitors (ICIs) were included in 58%, 47%, 32%, and 0% (Risk 0/I/II/III) during the course of treatment. In patients with MTT/ICI treatment, the estimated 1-year and 3-year post-recurrence survival rates were 88% and 58%, respectively. Conclusions: Risk classification for LEC was associated with survival after lung cancer surgery, as well as post-recurrence treatment. The concept of physical performance-preserving surgery may contribute to improving the outcomes of current lung cancer treatment.

DOI： 10.1007/s00268-021-06427-3

Scopus

Effect of Itraconazole and Its Metabolite Hydroxyitraconazole on the Blood Concentrations of Cyclosporine and Tacrolimus in Lung Transplant Recipients Reviewed

Matsuda Yuya, Nakagawa Shunsaku, Yano Ikuko, Masuda Satohiro, Imai Satoshi, Yonezawa Atsushi, Yamamoto Takashi, Sugimoto Mitsuhiro, Tsuda Masahiro, Tsuzuki Tetsunori, Omura Tomohiro, Nakagawa Takayuki, Chen-Yoshikawa Toyofumi Fengshi, Nagao Miki, Date Hiroshi, Matsubara Kazuo

Biological and Pharmaceutical Bulletin Vol. 45 ( 4 ) page： 397 - 402 2022.4

Language：English Publisher：The Pharmaceutical Society of Japan

Invasive Aspergillus infection is a major factor for poor prognosis in patients receiving lung transplantation (LT). An antifungal agent, itraconazole (ITCZ), that has antimicrobial activity against Aspergillus species, is used as a prophylactic agent against Aspergillus infection after LT. ITCZ and its metabolite, hydroxyitraconazole (OH-ITCZ), potently inhibit CYP3A and P-glycoprotein that metabolize or excrete calcineurin inhibitors (CNIs), which are the first-line immunosuppressants used after LT; thus, concomitant use of ITCZ and CNIs could induce an increase in the blood concentration of CNIs. However, no criteria for dose reduction of CNIs upon concomitant use with ITCZ in LT recipients have been defined. In this study, the effect of ITCZ and OH-ITCZ on the blood concentrations of two CNIs, tacrolimus and cyclosporine, after LT were retrospectively evaluated. A total of 39 patients who received LT were evaluated. Effects of ITCZ and OH-ITCZ on the concentration/dosage (C/D) ratio of tacrolimus and cyclosporine were analyzed using linear mixed-effects models. The plasma concentrations of OH-ITCZ were about 2.5-fold higher than those of ITCZ. Moreover, there was a significant correlation between the plasma concentrations of ITCZ and OH-ITCZ. Based on parameters obtained in the linear regression analysis, the C/D ratios of cyclosporine and tacrolimus increase by an average of 2.25- and 2.70-fold, respectively, when the total plasma concentration of ITCZ plus OH-ITCZ is 1000 ng/mL. In conclusion, the plasma levels of ITCZ and OH-ITCZ could be key factors in drawing up the criterion for dose reduction of CNIs.

DOI： 10.1248/bpb.b21-00738

Scopus

CiNii Research

Successful lung transplant cases with ex vivo lung perfusion assessment of extended criteria donor lungs. Reviewed

Daisuke Nakajima, Shunichi Nagata, Hidenao Kayawake, Satona Tanaka, Yoshito Yamada, Yojiro Yutaka, Akihiro Ohsumi, Masatsugu Hamaji, Toyofumi F Chen-Yoshikawa, Hiroshi Date

General thoracic and cardiovascular surgery Vol. 70 ( 4 ) page： 406 - 412 2022.4

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

We report our successful experience in two lung transplant cases in which ex vivo lung perfusion (EVLP) was used to evaluate the function of injured brain-dead donor lungs that were otherwise initially unacceptable. After the donor's lungs were declined for transplantation by all other transplant centers, the lungs were offered to the patients listed for lung transplantation in our hospital. The donor lung function was considered acceptable for transplantation after the 3-h EVLP assessment. In the first case, a 32-year-old man with bronchiolitis obliterans after hematopoietic stem cell transplantation underwent hybrid lung transplantation, that was right brain-dead donor lung transplantation, combined with native-upper lobe sparing living-donor lobar lung transplantation on the left side. In the second case, a 61-year-old woman received the right single lung transplantation for idiopathic pulmonary fibrosis. Both patients are doing well at one and a half years after lung transplantation.

DOI： 10.1007/s11748-022-01774-x

PubMed

ASO Visual Abstract: Pleural Invasion Depth of Disseminated Nodules in Patients with Stage IVa or Recurrent Thymoma: Assessment, Curative Impact, and Surgical Outcomes Reviewed

Nakamura S., Tateyama H., Nakanishi K., Sugiyama T., Kadomatsu Y., Ueno H., Goto M., Ozeki N., Fukui T., Yokoi K., Chen-Yoshikawa T.F.

Annals of surgical oncology Vol. 29 ( 3 ) 2022.3

Clinical, radiological and pathological features of idiopathic and secondary interstitial pneumonia with pleuroparenchymal fibroelastosis in patients undergoing lung transplantation Reviewed

Ikegami N., Nakajima N., Yoshizawa A., Handa T., Chen-Yoshikawa T., Kubo T., Tanizawa K., Ohsumi A., Yamada Y., Hamaji M., Nakajima D., Yutaka Y., Tanaka S., Watanabe K., Nakatsuka Y., Murase Y., Nakanishi T., Niwamoto T., Chin K., Date H., Hirai T.

Histopathology Vol. 80 ( 4 ) page： 665 - 676 2022.3

Language：English Publisher：Histopathology

Aims: Idiopathic pleuroparenchymal fibroelastosis (PPFE) is a rare type of idiopathic interstitial pneumonia, and pathological PPFE is also observed in patients with secondary interstitial pneumonia. This study aimed to evaluate the pathological findings associated with radiological PPFE-like lesions and the clinical and morphological features of patients with pathological PPFE. Methods and results: We retrospectively reviewed the pathology of the explanted lungs from 59 lung transplant recipients with radiological PPFE-like lesions. Pathological PPFE lesions were identified in 14 patients with idiopathic disease and in 12 patients with secondary disease. Pathological PPFE was associated with previous pneumothorax, volume loss in the upper lobes, and a flattened chest. Patients with idiopathic disease and those with secondary disease with pathological PPFE had similar clinical, radiological and pathological findings, whereas fibroblastic foci were more common in patients with idiopathic disease, and patients with secondary disease more frequently showed alveolar septal thickening with elastosis or fibrosis. Post-transplantation survival did not differ between patients with idiopathic and secondary disease with pathological PPFE (log-rank; P = 0.57) and was similar between patients with idiopathic disease with pathological PPFE and those with idiopathic pulmonary fibrosis (IPF) (log-rank; P = 0.62). Conclusions: Not all patients with interstitial pneumonia with radiological PPFE-like lesions have pathological PPFE. Characteristic clinical features can suggest the presence of pathological PPFE, and idiopathic and secondary cases with pathological PPFE are similar except for fibroblastic foci in idiopathic cases and alveolar septal thickening with elastosis or fibrosis in secondary cases. Patients with pathological PPFE have a similar prognosis to those with IPF after transplantation.

DOI： 10.1111/his.14595

Scopus

Pleural Invasion Depth of Disseminated Nodules in Patients with Stage IVa or Recurrent Thymoma: Assessment, Curative Impact, and Surgical Outcomes Reviewed

Nakamura S., Tateyama H., Nakanishi K., Sugiyama T., Kadomatsu Y., Ueno H., Goto M., Ozeki N., Fukui T., Yokoi K., Chen-Yoshikawa T.F.

Annals of Surgical Oncology Vol. 29 ( 3 ) page： 1829 - 1837 2022.3

Authorship：Last author Language：English Publisher：Annals of Surgical Oncology

Background: Thymoma patients with pleural dissemination are difficult to manage, and their treatment strategy remains undefined. This study aimed to investigate the clinicopathologic features of these patients, focusing on the association between the depth of pleural invasion and prognosis. Methods: Between 2003 and 2019, the study identified 120 disseminated lesions in 20 thymoma patients. Seven patients had de novo stage IVa thymoma and 13 were recurrent cases. Extrapleural pneumonectomy was performed for 8 patients and debulking surgery for 12 patients. Invasion depth of pleural tumors was classified into two groups: when the disseminated tumors invaded the pleura beneath the elastic layer, the tumor was diagnosed as Da, and when the disseminated tumors invaded the pleura beyond the elastic layer, the tumor was diagnosed as Db. Results: Of 120 nodules, 31 (26%), found in eight patients with recurrent malignancies, were classified as Db. The pathologic status of the surgical margin (PSM) was positive in eight patients, seven of whom had Db nodules. The 5-year overall survival (OS) rate was 100% in the Da group and 75% in the Db group (P = 0.02). The 5-year progression-free survival (PFS) rate was 66.7% in the Da group and 25% in the Db group (P = 0.02). Cox univariate analysis showed that PFS was significantly influenced by the depth of invasion (P = 0.04) and PSM (P = 0.03). Conclusion: Depth of pleural invasion may influence survival outcomes for thymoma patients with pleural dissemination. The patients in this study with Da-disseminated nodules had an increased probability of a longer OS and PFS and tended to achieve negative PSM compared with the patients with Db.

DOI： 10.1245/s10434-021-10888-0

Scopus

SRGN-Triggered Aggressive and Immunosuppressive Phenotype in a Subset of TTF-1-Negative Lung Adenocarcinomas Reviewed

Tanaka I., Dayde D., Tai M.C., Mori H., Solis L.M., Tripathi S.C., Fahrmann J.F., Unver N., Parhy G., Jain R., Parra E.R., Murakami Y., Aguilar-Bonavides C., Mino B., Celiktas M., Dhillon D., Casabar J.P., Nakatochi M., Stingo F., Baladandayuthapani V., Wang H., Katayama H., Dennison J.B., Lorenzi P.L., Do K.A., Fujimoto J., Behrens C., Ostrin E.J., Rodriguez-Canales J., Hase T., Fukui T., Kajino T., Kato S., Yatabe Y., Hosoda W., Kawaguchi K., Yokoi K., Chen-Yoshikawa T.F., Hasegawa Y., Gazdar A.F., Wistuba I.I., Hanash S., Taguchi A.

Journal of the National Cancer Institute Vol. 114 ( 2 ) page： 290 - 301 2022.2

Language：English Publisher：Journal of the National Cancer Institute

Background: Approximately 20% of lung adenocarcinoma (LUAD) is negative for the lineage-specific oncogene Thyroid transcription factor 1 (TTF-1) and exhibits worse clinical outcome with a low frequency of actionable genomic alterations. To identify molecular features associated with TTF-1-negative LUAD, we compared the transcriptomic and proteomic profiles of LUAD cell lines. SRGN, a chondroitin sulfate proteoglycan Serglycin, was identified as a markedly overexpressed gene in TTF-1-negative LUAD. We therefore investigated the roles and regulation of SRGN in TTF-1-negative LUAD. Methods: Proteomic and metabolomic analyses of 41 LUAD cell lines were done using mass spectrometry. The function of SRGN was investigated in 3 TTF-1-negative and 4 TTF-1-positive LUAD cell lines and in a syngeneic mouse model (n = 5 to 8 mice per group). Expression of SRGN was evaluated in 94 and 105 surgically resected LUAD tumor specimens using immunohistochemistry. All statistical tests were 2-sided. Results: SRGN was markedly overexpressed at mRNA and protein levels in TTF-1-negative LUAD cell lines (P <. 001 for both mRNA and protein levels). Expression of SRGN in LUAD tumor tissue was associated with poor outcome (hazard ratio = 4.22, 95% confidence interval = 1.12 to 15.86, likelihood ratio test, P =. 03), and with higher expression of Programmed cell death 1 ligand 1 (PD-L1) in tumor cells and higher infiltration of Programmed cell death protein 1-positive lymphocytes. SRGN regulated expression of PD-L1 as well as proinflammatory cytokines, including Interleukin-6, Interleukin-8, and C-X-C motif chemokine 1 in LUAD cell lines; increased migratory and invasive properties of LUAD cells and fibroblasts; and enhanced angiogenesis. SRGN was induced by DNA demethylation resulting from Nicotinamide N-methyltransferase-mediated impairment of methionine metabolism. Conclusions: Our findings suggest that SRGN plays a pivotal role in tumor-stromal interaction and reprogramming into an aggressive and immunosuppressive tumor microenvironment in TTF-1-negative LUAD.

DOI： 10.1093/jnci/djab183

Scopus

Changes in the health-related quality of life and social reintegration status after lung transplantation following hematopoietic stem cell transplantation Reviewed

Hamada R., Oshima Y., Sato S., Yoshioka Y., Nankaku M., Kondo T., Chen-Yoshikawa T.F., Ikeguchi R., Nakajima D., Date H., Matsuda S.

Supportive Care in Cancer Vol. 30 ( 2 ) page： 1831 - 1839 2022.2

Language：English Publisher：Supportive Care in Cancer

Purpose: Late-onset non-infectious pulmonary complications (LONIPCs) after allogeneic hematopoietic stem cell transplantation are fatal; however, lung transplantation might achieve good survival. Nevertheless, improving the health-related quality of life (HRQoL) is still a major concern. This study aimed to investigate, in detail, the recovery in HRQoL and social reintegration status after lung transplantation in patients with LONIPC after allo-HSCT. Methods: This prospective cohort study involving 18 patients examined changes in the health and social reintegration status after lung transplantation following LONIPC. Results: Physical function and HRQoL were lowest before lung transplantation. Two years after lung transplantation, the dyspnea scores and performance status improved. Most patients had made a successful return to society, and patients who achieved social reintegration were significantly younger and had a good performance status. However, their Physical Functioning score and Physical Component Summary did not show significant improvement after lung transplantation. Moreover, recipients who were unemployed before lung transplantation were likely to remain unemployed and continued to show poor HRQoL. Conclusions: These results showed poor recovery of HRQoL, especially in terms of physical function, and the likelihood of failure to reintegrate into society within 2 years after lung transplantation. It is necessary to consider long-term follow-up and physical training to improve social reintegration and HRQoL.

DOI： 10.1007/s00520-021-06592-0

Scopus

Protective effect of necrosulfonamide on rat pulmonary ischemia-reperfusion injury via inhibition of necroptosis Reviewed

Ueda S., Chen-Yoshikawa T.F., Tanaka S., Yamada Y., Nakajima D., Ohsumi A., Date H.

Journal of Thoracic and Cardiovascular Surgery Vol. 163 ( 2 ) page： e113 - e122 2022.2

Language：English Publisher：Journal of Thoracic and Cardiovascular Surgery

Background: Necroptosis plays an important role in cell death during pulmonary ischemia-reperfusion injury (IRI). We hypothesized that therapy with necrosulfonamide (NSA), a mixed-lineage kinase domain-like protein inhibitor, would attenuate lung IRI. Methods: Rats were assigned at random into the sham operation group (n = 6), vehicle group (n = 8), or NSA group (n = 8). In the NSA and vehicle groups, the animals were heparinized and underwent left thoracotomy, and the left hilum was clamped for 90 minutes, followed by reperfusion for 120 minutes. NSA (0.5 mg/body) and a solvent were administered i.p. in the NSA group and the vehicle group, respectively. The sham group underwent 210 minutes of perfusion without ischemia. After reperfusion, arterial blood gas analysis, physiologic data, lung wet-to-dry weight ratio, histologic changes, and cytokine levels were assessed. Fluorescence double immunostaining was performed to evaluate necroptosis and apoptosis. Results: Arterial partial pressure of oxygen/fraction of inspired oxygen (PaO2/FiO2) was better, dynamic compliance was higher, and mean airway pressure and lung edema were lower in the NSA group compared with the vehicle group. Moreover, in the NSA group, lung injury was significantly alleviated, and the mean number of necroptotic cells (55.3 ± 4.06 vs 78.2 ± 6.87; P =.024), but not of apoptotic cells (P =.084), was significantly reduced compared with the vehicle group. Interleukin (IL)-1β and IL-6 levels were significantly lower with NSA administration. Conclusions: In a rat model, our results suggest that NSA may have a potential protective role in lung IRI through the inhibition of necroptosis.

DOI： 10.1016/j.jtcvs.2021.01.037

Scopus

Meclozine Attenuates the MARK Pathway in Mammalian Chondrocytes and Ameliorates FGF2-Induced Bone Hyperossification in Larval Zebrafish Reviewed

Takemoto G., Matsushita M., Okamoto T., Ito T., Matsuura Y., Takashima C., Chen-Yoshikawa T.F., Ebi H., Imagama S., Kitoh H., Ohno K., Hosono Y.

Frontiers in Cell and Developmental Biology Vol. 9 2022.1

Language：English Publisher：Frontiers in Cell and Developmental Biology

Meclozine has been developed as an inhibitor of fibroblast growth factor receptor 3 (FGFR3) to treat achondroplasia (ACH). Extracellular signal regulated kinase (ERK) phosphorylation was attenuated by meclozine in FGF2-treated chondrocyte cell line, but the site of its action has not been elucidated. Although orally administered meclozine promoted longitudinal bone growth in a mouse model of ACH, its effect on craniofacial bone development during the early stage remains unknown. Herein, RNA-sequencing analysis was performed using murine chondrocytes from FGF2-treated cultured tibiae, which was significantly elongated by meclozine treatment. Gene set enrichment analysis demonstrated that FGF2 significantly increased the enrichment score of mitogen-activated protein kinase (MAPK) family signaling cascades in chondrocytes; however, meclozine reduced this enrichment. Next, we administered meclozine to FGF2-treated larval zebrafish from 8 h post-fertilization (hpf). We observed that FGF2 significantly increased the number of ossified vertebrae in larval zebrafish at 7 days post-fertilization (dpf), while meclozine delayed vertebral ossification in FGF2-induced zebrafish. Meclozine also reversed the FGF2-induced upregulation of ossified craniofacial bone area, including ceratohyal, hyomandibular, and quadrate. The current study provided additional evidence regarding the inhibitory effect of meclozine on the FGF2-induced upregulation of MAPK signaling in chondrocytes and FGF2-induced development of craniofacial and vertebral bones.

DOI： 10.3389/fcell.2021.694018

Scopus

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Papers - CHEN-YOSHIKAWA Toyofumi