563 results on '"Yoshinori Okada"'
Search Results
152. AMBRA1 controls antigen-driven activation and proliferation of naive T cells
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Minoru Kimura, Takehito Sato, Hiroyuki Hosokawa, Katsuto Hozumi, Yumi Iida, Ituro Inoue, Takahiro Suzuki, Kaori Masuhara, Mizuki Tokusanai, Chenyang Li, Masato Ohtsuka, Hisako Akatsuka, and Yoshinori Okada
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0301 basic medicine ,Programmed cell death ,Naive T cell ,T cell ,Immunology ,T-cell receptor ,General Medicine ,BECN1 ,Biology ,Cell biology ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,medicine.anatomical_structure ,Immune system ,Antigen ,medicine ,Immunology and Allergy ,Cytotoxic T cell ,030217 neurology & neurosurgery - Abstract
AMBRA1 (activating molecule in Beclin1-regulated autophagy) is a member of the BECN1 (BECLIN1) protein complex, and it plays a role in autophagy, cell death, tumorigenesis and proliferation. We recently reported that on T-cell receptor (TCR) stimulation, AMBRA1 controlled both autophagy and the cell cycle with metabolic regulation. Accumulating evidence has shown that autophagy and metabolic control are pivotal for T-cell activation, clonal expansion and effector/memory cell fate decision. However, it is unknown whether AMBRA1 is involved in T-cell function under physiological conditions. We found that T cells in Ambra1-conditional knockout (cKO) mice induced an exacerbated graft versus host response when they were transplanted into allogeneic BALB/c mice. Furthermore, Ambra1-deficient T cells showed increased proliferation and cytotoxic capability toward specific antigens in response to in vivo stimulation using allogeneic spleen cells. This enhanced immune response mainly contributed to naive T-cell hyperactivity. The T-cell hyperactivity observed in this study was similar to those in some metabolic factor-deficient mice, but not those in other pro-autophagic factor-deficient mice. Under the static condition, however, naive T cells were reduced in Ambra1-cKO mice, the same as in pro-autophagic factor-deficient mice. Collectively, these results suggested that AMBRA1 was involved in regulating T cell-mediated immune responses through autophagy-dependent and -independent mechanisms.
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- 2020
153. A phase 2 study of adjuvant carboplatin plus S-1 followed by maintenance S-1 therapy for patients with completely resected stage II/IIIA non-small cell lung cancer—Japanese Northern East Area Thoracic Surgery Study Group JNETS1302 study
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Motoyasu Sagawa, Hidetaka Uramoto, Tohru Hasumi, Satomi Takahashi, Hiroyuki Oura, Hiroyuki Suzuki, Jiro Abe, Chiaki Endo, Hajime Saito, Yoshinori Okada, Akira Sakurada, Hiroyuki Deguchi, Takeo Hasegawa, and Nobuyuki Sato
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0301 basic medicine ,Pulmonary and Respiratory Medicine ,Oncology ,medicine.medical_specialty ,medicine.medical_treatment ,non-small cell lung cancer (NSCLC) ,Vinorelbine ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Internal medicine ,medicine ,Lung cancer ,Survival rate ,Chemotherapy ,business.industry ,medicine.disease ,Carboplatin ,Regimen ,030104 developmental biology ,chemistry ,Tolerability ,030220 oncology & carcinogenesis ,Original Article ,business ,medicine.drug - Abstract
BACKGROUND: The standard adjuvant chemotherapy regimen for completely resected pathological stage II/IIIA non-small cell lung cancer (NSCLC) is four courses of cisplatin plus vinorelbine. However, the continuity and toxicity of cisplatin-based regimens remain problematic. Conversely, carboplatin-based chemotherapy is a less toxic and more tolerable regimen for various stages of NSCLC. In particular, the efficacy and tolerability of carboplatin plus S-1 in advanced NSCLC were confirmed by previous pivotal studies such as the LETS trail. Therefore, this phase II study assessed the feasibility, safety, and usefulness of carboplatin plus S-1 followed by maintenance S-1 as an adjuvant treatment. METHODS: In this single-arm, multicenter phase II study, 40 patients who previously underwent complete resection of NSCLC were enrolled from November 2013 to January 2015. The chemotherapy protocol was four cycles of carboplatin (AUC 5 on day 1) and oral S-1 (80 mg/m(2) every other day from days 1 to 21) followed by oral S-1 (80 mg/m(2) every other day for 48 weeks). The primary endpoint was the treatment completion rate, and the secondary endpoints were adverse events and 2-year recurrence-free survival. RESULTS: The treatment completion rate of the planned schedule was as low as 30.0% (90% confidence interval: 40.3–63.0%). The reasons for adjuvant chemotherapy discontinuation were adverse events, refusal, tumor recurrence, and other reasons in 13, 6, 10, and 2 patients, respectively. The 2-year progression-free survival rate was 66.7% among patients who completed maintenance chemotherapy. There were no treatment-related deaths, and most adverse events were less than grade 3. CONCLUSIONS: Carboplatin plus S-1 followed by S-1 maintenance for 1 year in the adjuvant treatment of NSCLC was not tolerable, although most adverse events were not severe. However, patients who can fully complete the regimen might experience clinical benefit.
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- 2020
154. Podoplanin is indispensable for cell motility and platelet-induced epithelial-to-mesenchymal transition-related gene expression in esophagus squamous carcinoma TE11A cells
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Masako Kidokoro, Hisako Akatuska, Takehito Sato, Nobuo Watanabe, Yumi Iida, Noriaki Hirayama, Makiko Tanaka, Shigeaki Inoue, Sadaki Inokuchi, Yusuke Suzuki, Takashi Yahata, Yoshihide Nakagawa, Chisa Okada, Tomoatsu Tsuji, and Yoshinori Okada
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Cancer Research ,Cell signaling ,Motility ,Vimentin ,lcsh:RC254-282 ,Metastasis ,03 medical and health sciences ,0302 clinical medicine ,Esophageal squamous cell carcinoma ,Genetics ,Epithelial–mesenchymal transition ,Platelet activation ,lcsh:QH573-671 ,PDPN ,030304 developmental biology ,0303 health sciences ,biology ,lcsh:Cytology ,Platelet ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,Crispr-Cas-9 ,Squamous carcinoma ,Oncology ,Podoplanin ,030220 oncology & carcinogenesis ,biology.protein ,Cancer research ,Knockdown ,Primary Research - Abstract
Background The transmembrane glycoprotein podoplanin (PDPN) is upregulated in some tumors and has gained attention as a malignant tumor biomarker. PDPN molecules have platelet aggregation-stimulating domains and, are therefore, suggested to play a role in tumor-induced platelet activation, which in turn triggers epithelial-to-mesenchymal transition (EMT) and enhances the invasive and metastatic activities of tumor cells. In addition, as forced PDPN expression itself can alter the propensity of certain tumor cells in favor of EMT and enhance their invasive ability, it is also considered to be involved in the cell signaling system. Nevertheless, underlying mechanisms of PDPN in tumor cell invasive ability as well as EMT induction, especially by platelets, are still not fully understood. Methods Subclonal TE11A cells were isolated from the human esophageal squamous carcinoma cell line TE11 and the effects of anti-PDPN neutralizing antibody as well as PDPN gene knockout on platelet-induced EMT-related gene expression were measured. Also, the effects of PDPN deficiency on cellular invasive ability and motility were assessed. Results PDPN-null cells were able to provoke platelet aggregation, suggesting that PDPN contribution to platelet activation in these cells is marginal. Nevertheless, expression of platelet-induced EMT-related genes, including vimentin, was impaired by PDPN-neutralizing antibody as well as PDPN deficiency, while their effects on TGF-β-induced gene expression were marginal. Unexpectedly, PDPN gene ablation, at least in either allele, engendered spontaneous N-cadherin upregulation and claudin-1 downregulation. Despite these seemingly EMT-like alterations, PDPN deficiency impaired cellular motility and invasive ability even after TGF-β-induced EMT induction. Conclusions These results suggested that, while PDPN seems to function in favor of maintaining the epithelial state of this cell line, it is indispensable for platelet-mediated induction of particular mesenchymal marker genes as well as the potentiation of motility and invasion capacity.
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- 2020
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155. Correlation between preoperative
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Hisashi, Oishi, Akira, Sakurada, Hirotsugu, Notsuda, Ryota, Tanaka, Kentaro, Takanami, Ryoko, Saito, Shunsuke, Eba, Masafumi, Noda, and Yoshinori, Okada
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Aged, 80 and over ,Male ,Lung Neoplasms ,Time Factors ,Middle Aged ,Prognosis ,Survival Rate ,Fluorodeoxyglucose F18 ,Carcinoma, Non-Small-Cell Lung ,Positron Emission Tomography Computed Tomography ,Preoperative Period ,Humans ,Female ,Idiopathic Interstitial Pneumonias ,Postoperative Period ,Pneumonectomy ,Aged - Abstract
The present study aimed to investigate the correlation between preoperative 2-deoxy-2-[We retrospectively reviewed the data of 425 patients who underwent lung resection for non-small cell lung cancer without preoperative radiation therapy between November 2012 and October 2017. The maximum SUV (SUVmax) in the IIP area except the lung cancer site was measured in each patient.Thirty-one of the 425 patients (7.3%) showed findings of IIP in chest CT. Five of the 31 patients (16.1%) developed acute exacerbation (AE) after lung resection (AE+ group). Twenty-six of the 31 patients (83.9%) did not develop AE (AE- group). In the AE+ group
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- 2020
156. [Schloffer Tumor that Appeared and Increased 40 Months after Resection of Lung Cancer and was Suspected of Recurrence of Pleural Dissemination]
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Shunsuke, Eba, Masaki, Shimoji, Masahide, Hirose, Shinichiro, Ota, and Yoshinori, Okada
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Lung Neoplasms ,Thoracic Surgery, Video-Assisted ,Positron Emission Tomography Computed Tomography ,Humans ,Female ,Middle Aged ,Neoplasm Recurrence, Local ,Tomography, X-Ray Computed - Abstract
The case is a 50-year-old woman. Video-assisted thoracic surgery (VATS) left upper division segmentectomy was performed for adenocarcinoma through a postero-lateral incision. The pathological result was stage ⅠA. A chest computed tomography (CT) examination 40 months after the operation revealed a nodule in contact with the left 6th rib. A recurrence due to pleural dissemination was suspected in the PET/CT examination, but the possibility of reactive granulation was also considered. Two months later, chest CT reexamination showed an enlargement of the nodule, and reoperation was performed. A fibrous structure that appears to be a silk thread for closing chest at the 1st operation was found on the chest wall. The pathological examination revealed chronic suppurative pleuritis and organizing pneumonia without malignancy, leading to a diagnosis of Schloffer tumor.
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- 2020
157. Stanniocalcin-1 (STC1) Affects SMAD7 Epigenetics, Increases Glutathione Synthesis and Ameliorate Bleomycin Fibrosis Through Regulating Integrated Metabolic Pathways
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Yoshinori Okada, Tokiwa Tamai, Masao Tabata, Hiromasa Ogawa, Hajime Kurosawa, Shinya Ohkouchi, Toshiya Irokawa, and Masahiko Kanehira
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Metabolic pathway ,chemistry.chemical_compound ,chemistry ,Stanniocalcin ,Fibrosis ,Cancer research ,medicine ,STC1 ,Glutathione synthesis ,Epigenetics ,Biology ,medicine.disease ,Bleomycin - Published
- 2020
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158. Enhancer Remodeling Promotes Tumor-Initiating Activity in NRF2-Activated Non-Small Cell Lung Cancers
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Md. Morshedul Alam, Shu Tadaka, Daisuke Matsumaru, Nao Ota, Yoshinori Okada, Takuma Suzuki, Hiroki Sekine, Zun Liu, Fumiki Katsuoka, Hozumi Motohashi, Masayuki Yamamoto, Hayato Anzawa, Takashi Suzuki, Yoshiaki Onodera, Keito Okazaki, Akira Sakurada, Kengo Kinoshita, Mika Watanabe, Hiroshi Kitamura, and Ikuko N. Motoike
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Lung ,Cell ,Biology ,respiratory system ,Malignancy ,medicine.disease ,medicine.disease_cause ,digestive system ,environment and public health ,respiratory tract diseases ,medicine.anatomical_structure ,medicine ,CEBPB ,Cancer research ,Epigenetics ,Enhancer ,Carcinogenesis ,Gene - Abstract
SummaryTranscriptional dysregulation, which can be caused by genetic and epigenetic alterations, is a fundamental feature of many cancers. A key cytoprotective transcriptional activator, NRF2, is often aberrantly activated in non-small cell lung cancers (NSCLCs) and supports both aggressive tumorigenesis and therapeutic resistance. Herein, we found that persistently activated NRF2 in NSCLCs generates enhancers at gene loci that are not normally regulated by transiently activated NRF2 under physiological conditions. Elevated accumulation of CEBPB in NRF2-activated NSCLCs was found to be one of the prerequisites for establishment of the unique NRF2-dependent enhancers, among whichNOTCH3enhancer was shown to be critical for the promotion of tumor-initiating activity. Enhancer remodeling mediated by NRF2-CEBPB cooperativity promotes tumor-initiating activity and drives malignancy of NRF2-activated NSCLCs via establishment of the NRF2-NOTCH3 regulatory axis.
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- 2020
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159. Three-dimensional electronic structure in ferromagnetic Fe3Sn2 with breathing kagome bilayers
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Ryo Noguchi, Cephise Cacho, Yoshinori Okada, Takeshi Kondo, Barnaby Smith, Cédric Bareille, Sungwon Jung, Yuita Fujisawa, Kenta Kuroda, Hiroaki Tanaka, Takayuki Muro, and Shunsuke Sakuragi
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Materials science ,Condensed matter physics ,Photoemission spectroscopy ,Weyl semimetal ,Angle-resolved photoemission spectroscopy ,02 engineering and technology ,Electronic structure ,021001 nanoscience & nanotechnology ,01 natural sciences ,Ferromagnetism ,Hall effect ,0103 physical sciences ,Condensed Matter::Strongly Correlated Electrons ,Density functional theory ,010306 general physics ,0210 nano-technology ,Surface states - Abstract
A large anomalous Hall effect (AHE) has been observed in ferromagnetic ${\mathrm{Fe}}_{3}{\mathrm{Sn}}_{2}$ with breathing kagome bilayers. To understand the underlying mechanism for this, we investigate the electronic structure of ${\mathrm{Fe}}_{3}{\mathrm{Sn}}_{2}$ by angle-resolved photoemission spectroscopy (ARPES). In particular, we use both vacuum ultraviolet light (VUV) and soft x ray (SX), which allow surface-sensitive and relatively bulk-sensitive measurements, respectively, and distinguish bulk states from surface states, which should be unlikely related to the AHE. While VUV-ARPES observes two-dimensional bands mostly due to surface states, SX-ARPES reveals three-dimensional band dispersions with a periodicity of the rhombohedral unit cell in the bulk. Our data show a good consistency with a theoretical calculation based on density functional theory, suggesting a possibility that ${\mathrm{Fe}}_{3}{\mathrm{Sn}}_{2}$ is a magnetic Weyl semimetal.
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- 2020
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160. Plasma mycophenolic acid concentration and the clinical outcome after lung transplantation
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Yasushi Matsuda, Takashi Hirama, Fumihiko Hoshi, Tatsuaki Watanabe, Hisashi Oishi, Masafumi Kikuchi, Akira Sakurada, Hiroshi Yabuki, Masafumi Noda, Shunsuke Eba, Tetsu Sado, Hiroaki Yamaguchi, Nariyasu Mano, and Yoshinori Okada
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Adult ,medicine.medical_specialty ,medicine.medical_treatment ,030230 surgery ,Gastroenterology ,Mycophenolic acid ,Tacrolimus ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,medicine ,Lung transplantation ,Humans ,Adverse effect ,Transplantation ,Lung ,medicine.diagnostic_test ,Receiver operating characteristic analysis ,business.industry ,Mycophenolic Acid ,Kidney Transplantation ,medicine.anatomical_structure ,Therapeutic drug monitoring ,Area Under Curve ,030211 gastroenterology & hepatology ,business ,Immunosuppressive Agents ,medicine.drug ,Lung Transplantation - Abstract
Background The therapeutic drug monitoring of mycophenolic acid (MPA) has been investigated for renal and heart transplantations; however, its usefulness in lung transplantation is unclear. Methods The MPA area under the plasma concentration-time curve (AUC) was calculated in 59 adult lung transplant recipients. The MPA AUC0-12 s were compared among the three groups determined by the presence of adverse events (no events, infection, and chronic lung allograft dysfunction [CLAD]). Next, MPA AUC0-12 thresholds for the adverse events were identified by receiver operating characteristic analysis. Cumulative occurrence rate of the adverse events was compared between two groups (adequate and inadequate groups) according to the thresholds. Results The MPA AUC0-12 s in the no event, infection, and CLAD groups were 30.3 ± 6.5, 36.8 ± 10.7, and 20.6 ± 9.6 µg·h/mL, respectively (P = .0027), while the tacrolimus trough levels were similarly controlled in the groups. The thresholds of MPA AUC0-12 for the occurrence of infection and CLAD were 40.5 and 22.8 µg·h/mL, respectively. The cumulative occurrence rate of adverse events of adequate group (15.3%) was significantly lower than that of inadequate group (56.0%) (P = .0050). Conclusions The MPA AUC0-12 may affect the occurrence of adverse events in lung transplant recipients.
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- 2020
161. Development of a precise quantitative method for monitoring sirolimus in whole blood using LC/ESI-MS/MS
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Nariyasu Mano, Yoshinori Okada, Tetsu Sado, Shinya Takasaki, Yasushi Matsuda, Hisashi Oishi, Masafumi Noda, Masaki Tanaka, Masafumi Kikuchi, Kensuke Shigeta, and Hiroaki Yamaguchi
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Spectrometry, Mass, Electrospray Ionization ,Electrospray ionization ,Clinical Biochemistry ,Liquid-Liquid Extraction ,Magnetic immunoassay ,Ion suppression in liquid chromatography–mass spectrometry ,Tandem mass spectrometry ,030226 pharmacology & pharmacy ,01 natural sciences ,Biochemistry ,Sensitivity and Specificity ,Analytical Chemistry ,03 medical and health sciences ,0302 clinical medicine ,Tandem Mass Spectrometry ,Drug Discovery ,medicine ,Humans ,Lymphangioleiomyomatosis ,Molecular Biology ,Whole blood ,Pharmacology ,Immunoassay ,Sirolimus ,Chromatography ,medicine.diagnostic_test ,Chemistry ,010401 analytical chemistry ,Reproducibility of Results ,General Medicine ,Organ Transplantation ,medicine.disease ,0104 chemical sciences ,Therapeutic drug monitoring ,Linear Models ,Drug Monitoring ,Immunosuppressive Agents ,medicine.drug ,Chromatography, Liquid - Abstract
Sirolimus is used on patients after solid organ transplantation and on lymphangioleiomyomatosis (LAM) patients, and therapeutic drug monitoring is required in clinical practice. We have previously reported an accurate method for quantitative determination of sirolimus, but its sample preparation step was complicated. In this study, we developed a modified liquid chromatography/electrospray ionization tandem mass spectrometry (LC/ESI-MS/MS) method for sirolimus quantification. A supported liquid extraction cartridge was used to purify sirolimus from whole blood and ion suppression was mostly prevented. The validation results met the acceptance criteria. This method was compared with the antigen conjugated magnetic immunoassay (ACMIA) and our previously reported method, using whole blood samples from LAM patients. Comparison of the Bland-Altman plots of the currently developed method and the previous method revealed no significant difference between the two methods (mean bias, -2.02%; 95% CI, -7.81-3.78). The values obtained using ACMIA were significantly higher than those obtained using the current method by 13.87% (95% CI, 6.49-21.25) owing to cross-reactivity. The degrees of cross reactivities in LAM patients and in organ transplant patients were similar, and our LC/ESI-MS/MS method precisely measured the blood concentrations of sirolimus.
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- 2020
162. Validation of the Proposed cN2 Subclassification in the Eighth Edition of the IASLC Staging System: A Prospective Phase II Multicenter Study
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Motoyasu Sagawa, Masaya Aoki, Masami Sato, Hirohisa Kato, Hiroyuki Oura, Satoshi Shiono, Yuji Matsumura, Akira Sakurada, Yoshinori Okada, Hiroyuki Oizumi, Muneo Minowa, and Jiro Abe
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Pulmonary and Respiratory Medicine ,medicine.medical_specialty ,business.industry ,medicine.medical_treatment ,Prospective phase II ,Phases of clinical research ,Induction chemotherapy ,Perioperative ,Single-station cN2 ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,lcsh:RC254-282 ,Confidence interval ,5-Year overall survival ,Surgery ,Skip metastasis ,Pneumonectomy ,Bilobectomy ,Oncology ,medicine ,Non–small cell lung cancer ,Original Article ,Prospective cohort study ,business ,Chemoradiotherapy - Abstract
Introduction Surgery for N2 stage IIIA NSCLC is not recommended in major guidelines. Nevertheless, it has been noted that single-station N2 may have a better prognosis than multistation N2 and that surgery can be performed as the main therapeutic option. Methods We conducted a prospective phase II study for single-station clinical N2 (cN2) NSCLC to evaluate the efficacy and safety of surgical resection without induction therapy. Complete resection with lobectomy, bilobectomy, or pneumonectomy followed by ipsilateral mediastinal lymphadenectomy was performed in 32 of 34 enrolled patients, whereas the remaining two patients underwent incomplete resection. Three-quarters of the patients underwent subsequent adjuvant chemotherapy. Results The 5-year overall survival rate was 58.5% (95% confidence interval: 41.9–75.4) for all 34 patients, and eight patients (23.5%) with pN0 or pN1 seemed to have been enrolled. The 5-year overall survival rates for single-station cN2 without and with hilar node enlargement were 81.3% and 37.5%, respectively (p = 0.025). Surgical mortality was 0% for all, and no considerable perioperative complications were noted; however, two patients died of interstitial pneumonia and unknown cause within 3 months after surgical resection. Conclusions This is the very first prospective study on the surgical approach for cN2 NSCLC, and our result partially validated the proposed classification of the N descriptor in the new staging system. The treatment for single-station cN2 without hilar node enlargement would better if it were similar to that for cN1 disease. Induction chemotherapy or chemoradiotherapy may not be needed for such an entity.
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- 2020
163. Decreased expression of a phagocytic receptor Siglec-1 on alveolar macrophages in chronic obstructive pulmonary disease
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Mitsuhiro Yamada, Naoya Fujino, Masakazu Ichinose, Rie Tanaka, Yoshinori Okada, Satoshi O. Suzuki, Hirohito Sano, Hisatoshi Sugiura, Atsushi Tanno, and Taizou Hirano
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Male ,0301 basic medicine ,Sialic Acid Binding Ig-like Lectin 1 ,Phagocytosis ,CD36 ,Gene Expression ,Complement receptor ,Alveolar macrophage ,Pulmonary Disease, Chronic Obstructive ,03 medical and health sciences ,0302 clinical medicine ,Macrophages, Alveolar ,medicine ,Humans ,Macrophage ,Receptor ,Cells, Cultured ,Aged ,lcsh:RC705-779 ,Phagocytes ,Lung ,Siglec-1 ,biology ,business.industry ,Research ,Chronic obstructive pulmonary disease ,lcsh:Diseases of the respiratory system ,Middle Aged ,respiratory system ,Flow Cytometry ,Respiratory Function Tests ,030104 developmental biology ,medicine.anatomical_structure ,030228 respiratory system ,Integrin alpha M ,Immunology ,biology.protein ,Female ,business - Abstract
Background Alveolar macrophages are professional phagocytes that remove microbial pathogens inhaled into the lung. The phagocytic ability is compromised in chronic obstructive pulmonary disease (COPD). However, the molecular mechanisms underlying this defect in phagocytosis are not clearly defined. Materials and methods Cell suspensions were collected from lung tissues of patients undergoing lung resection. Alveolar macrophages were detected as FSChi/ SSChi/CD45+/CD206+ cells in the isolated cell suspension by flow-cytometry. The cell surface expression of plasma membrane-bound phagocytic receptors (Fcγ receptor I (FcγRI), a complement receptor CD11b, macrophage scavenger receptor-1 (MSR-1), CD36 and Siglec-1) was determined on the alveolar macrophages. Correlations between the expression levels of the phagocytic receptors and disease severity were analysed. Phagocytosis of fluorescence-tagged bacteria by human alveolar macrophages was evaluated. Results The flow-cytometry analyses revealed that FcγRI, CD11b, MSR-1 and Siglec-1, but not CD36, were expressed on human alveolar macrophages. Among these receptors, Siglec-1 expression was significantly decreased on alveolar macrophages in COPD ex-smokers (n = 11), compared to control never-smokers (n = 11) or control ex-smokers (n = 9). The Siglec-1 expression on alveolar macrophages was significantly correlated with lung function (forced expiratory volume in 1 s) and with the severity of emphysema. Treatment of human alveolar macrophages with an anti-Siglec1 blocking antibody decreased phagocytosis of non-typeable Haemophilus influenzae (NTHi). Conclusion Our findings demonstrated reduced expression of Siglec-1 on alveolar macrophages in COPD, which is involved in engulfment of NTHi.
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- 2020
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164. Improvement of native pulmonary alveolar proteinosis after contralateral single living-donor lobar lung transplantation: A case report
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Yoji Sasahara, Hajime Kurosawa, Miki Akiba, Ryoko Saito, Yoshinori Okada, Tatsuaki Watanabe, Kazuma Kobayashi, Masahito Ebina, Koh Nakata, Shinya Ohkouchi, Hisashi Oishi, and Tetsu Sado
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Transplantation ,Pathology ,medicine.medical_specialty ,Lung ,business.industry ,Anemia ,Alveolar proteinosis ,medicine.medical_treatment ,030232 urology & nephrology ,Bronchiolitis obliterans ,030230 surgery ,medicine.disease ,03 medical and health sciences ,0302 clinical medicine ,medicine.anatomical_structure ,Pediatrics, Perinatology and Child Health ,Medicine ,Lung transplantation ,business ,Pulmonary alveolar proteinosis ,Surfactant homeostasis ,Rare disease - Abstract
PAP is a rare disease characterized by the accumulation of surfactant materials in the alveolar spaces due to the imbalance of surfactant homeostasis (production and clearance). We herein report a case of an 8-year-old girl who developed PAP after BMT from her mother for the treatment of DBA. The anemia was improved by BMT; however, respiratory dysfunction due to graft-versus-host disease gradually progressed. She eventually underwent right single LDLLT from her mother when she was 14 years old. A pathological examination of the excised lung confirmed the finding of diffuse bronchiolitis obliterans and unexpectedly revealed widespread alveolar proteinosis. Interestingly, the GGO of her native left lung on chest X-ray was improved after LDLLT. We present the very unique clinical course of this patient and discuss the mechanisms underlying the development of PAP after BMT and its improvement after LDLLT from the same donor.
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- 2020
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165. Clinicopathological Profiling of Lung Carcinoids with a Ki67 Index > 20%
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Yoshinori Okada, Yuichi Ishikawa, Wilko Weichert, Hiroyoshi Suzuki, Toru Kameya, Atsuko Kasajima, Günter Klöppel, Björn Konukiewitz, Hironobu Sasano, Akira Sakurada, and Naomi Oka
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medicine.medical_specialty ,Lung ,Proliferative index ,Endocrine and Autonomic Systems ,business.industry ,Retinoblastoma ,Endocrinology, Diabetes and Metabolism ,Poorly differentiated ,030209 endocrinology & metabolism ,medicine.disease ,Gastroenterology ,030218 nuclear medicine & medical imaging ,Well differentiated ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,0302 clinical medicine ,Endocrinology ,medicine.anatomical_structure ,Internal medicine ,Ki67 index ,Medicine ,Immunohistochemistry ,business ,Atypical carcinoid - Abstract
The clinicopathological features of lung neuroendocrine neoplasms (NEN) with a high proliferative index at the border area between atypical carcinoid and neuroendocrine carcinoma have not been investigated so far. The aim of this study was, therefore, to search for lung NENs which are well differentiated but show Ki67 values that overlap with those of poorly differentiated (PD)-NENs. Resected lung NENs from 244 Japanese patients were reviewed, and Ki67 indices were assessed in all tumors. The data were then correlated to clinicopathological parameters and patient outcome. Among 59 (24%) well-differentiated (WD)-NENs and 185 (76%) lung PD-NENs, 7 were defined as WD-NENs with Ki67 indices > 20%. The Ki67 indices of these tumors (mean 29%, range 24–36) were significantly lower than those of PD-NENs (mean 74%, range 34–99). All WD-NENs with Ki67 > 20% lacked abnormal p53 and loss of retinoblastoma 1 (Rb1) expression. In contrast, many PD-NENs expressed p53 (48%) and showed loss of Rb1 (86%). The 2- and 5-year disease-free survival rates in WD-NEN patients with Ki67 > 20% were lower than those of WD-NEN patients with Ki67 ≤20% (p < 0.01 for disease-free and overall survival). No statistical differences were detected between outcome of WD-NEN patients with Ki67 > 20% and those of PD-NEN. It is concluded that WD-NEN patients with Ki67 > 20% share the morphological and immunohistochemical features of WD-NEN patients with Ki67 ≤20%, but they have a worse prognosis, suggesting that this tumor group requires particular attention in future classifications and probably new therapeutic regimes.
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- 2018
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166. Management of De Novo Mycobacterial Infection After Lung Transplantation Without Rifampicin: Case Series of a Single Institution
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Hisashi Oishi, Hirotoshi Suzuki, Tatsuaki Watanabe, Mitsuhiro Yamada, Yasushi Matsuda, Yoshinori Okada, Tetsu Sado, Masafumi Noda, and Tsutomu Tamada
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Adult ,Male ,medicine.medical_specialty ,Tuberculosis ,medicine.medical_treatment ,Calcineurin Inhibitors ,Mycobacterium Infections, Nontuberculous ,Tacrolimus ,Organ transplantation ,03 medical and health sciences ,Postoperative Complications ,0302 clinical medicine ,Clarithromycin ,Internal medicine ,medicine ,Humans ,Lung transplantation ,Drug Interactions ,030212 general & internal medicine ,Ethambutol ,Retrospective Studies ,Immunosuppression Therapy ,Mycobacterium Infections ,Transplantation ,business.industry ,Incidence ,Nontuberculous Mycobacteria ,Immunosuppression ,Mycobacterium tuberculosis ,Middle Aged ,Mycophenolic Acid ,medicine.disease ,Anti-Bacterial Agents ,030228 respiratory system ,Cyclosporine ,Drug Therapy, Combination ,Female ,Surgery ,Rifampin ,business ,Immunosuppressive Agents ,Rifampicin ,Lung Transplantation ,medicine.drug - Abstract
Background and Objectives To treat organ transplant patients with mycobacterial infection, physicians need to pay attention to interaction between drugs used against mycobacteria and immunosuppressants. The purpose of this report is to describe the clinical features of and treatment for mycobacterial infection in lung transplant (LTx) recipients. Methods To investigate the incidence, treatment, and outcome for mycobacterial infection, we retrospectively reviewed 100 LTx recipients in our program since 2000. Results Four recipients (4.0%) developed mycobacterial infection. Three recipients took tacrolimus, and 1 received cyclosporine with mycophenolate mofetil and a steroid for immunosuppression. Tuberculosis (TB) was isolated from 2 recipients, and non-tuberculous mycobacteriosis (NTM) was detected in the other 2. We treated the patients with levofloxacin + isoniazid + pyrazinamide + ethambutol (EB) for TB and clarithromycin (CLM) + EB for NTM to avoid interaction of calcineurin inhibitors (CNI: 8-10 ng/mL in trough level) with rifampicin (RFP). In treating the patients with NTM, we were able to maintain an adequate blood concentration of CNI by decreasing the dosage from one-half to one-quarter. All mycobacterial infections were controlled with treatment. In 1 patient with chronic obstructive pulmonary disease (COPD) infected with TB in the native lung, the forced expiratory volume in 1 second (FEV1) unexpectedly increased from 1890 mL before infection to 2320 mL possibly due to organization of the native lung. Conclusions We were able to manage the mycobacterial infections using drugs other than RFP without any cases of acute rejection under adequate immunosuppression. Organization of the native lung with TB infection unexpectedly resulted in improvement of FEV1 in a COPD patient.
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- 2018
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167. Risk assessments for broncho-pleural fistula and respiratory failure after lung cancer surgery by National Clinical Database Japan
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Yoshihisa Shimada, Jun Nakajima, Shinichi Toyooka, Takashi Kondo, Yoshinori Okada, Masayuki Chida, Meinoshin Okumura, Hiroaki Miyata, Masami Sato, Eriko Fukuchi, Haruhiko Kondo, Shunsuke Endo, Ichiro Yoshino, Morihito Okada, Yukio Sato, and Norihiko Ikeda
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Male ,Pulmonary and Respiratory Medicine ,medicine.medical_specialty ,Lung Neoplasms ,Databases, Factual ,030204 cardiovascular system & hematology ,Nationwide survey ,Risk Assessment ,03 medical and health sciences ,Postoperative Complications ,Sex Factors ,0302 clinical medicine ,Japan ,Risk Factors ,Surgical oncology ,medicine ,Humans ,Pneumonectomy ,Aged ,Lung cancer surgery ,business.industry ,General surgery ,General Medicine ,Middle Aged ,Pleural Diseases ,Cardiac surgery ,030228 respiratory system ,Respiratory failure ,Cardiothoracic surgery ,Female ,Surgery ,Bronchial Fistula ,Pleural fistula ,Respiratory Insufficiency ,Cardiology and Cardiovascular Medicine ,Risk assessment ,business - Abstract
Background Broncho-pleural fistula (BPF) and respiratory failure (RF) are life-threatening complications after lung cancer surgery and can result in long-term hospitalization and decreased quality of life. Risk assessments for BPF and RF in addition to mortality and major morbidities are indispensable in surgical decision-making and perioperative care. Methods The characteristics and operative data of 80,095 patients who had undergone lung cancer surgery were derived from the 2014 and 2015 National Clinical Database (NCD) of Japan datasets. After excluding 1501 patients, risk models were developed from these data and validated by another dataset for 42,352 patients derived from the 2016 NCD dataset. Receiver operating characteristic curves were generated for postoperative BPF and RF development. The concordance-index was used to assess the discriminatory ability and validity of the model. Results BPF and RF occurred in 259 (0.3%) and 420 patients (0.5%), respectively, in the model development dataset and in 129 (0.3%) and 198 patients (0.5%), respectively, in the model validation dataset. Characteristic variables including types of surgery and comorbidities were identified as risk factors for BPF and RF, respectively. The concordance indexes of assessments for BPF and RF were 0.847 (p
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- 2018
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168. Disorder induced power-law gaps in an insulator–metal Mott transition
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Patrick Clancy, Tom Hogan, Luiz Santos, Vidya Madhavan, Yoshinori Okada, Nandini Trivedi, Stephen D. Wilson, Yongfeng Hu, Young-June Kim, Daniel Walkup, Wenwen Zhou, Jared O'Neal, Chetan Dhital, and Zhenyu Wang
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Physics ,Condensed Matter::Quantum Gases ,Multidisciplinary ,Condensed matter physics ,Strongly Correlated Electrons (cond-mat.str-el) ,Mott insulator ,Doping ,FOS: Physical sciences ,Fermi energy ,02 engineering and technology ,021001 nanoscience & nanotechnology ,01 natural sciences ,law.invention ,Mott transition ,Condensed Matter - Strongly Correlated Electrons ,law ,Physical Sciences ,0103 physical sciences ,Density of states ,Antiferromagnetism ,Condensed Matter::Strongly Correlated Electrons ,Scanning tunneling microscope ,010306 general physics ,0210 nano-technology ,Spectroscopy - Abstract
A correlated material in the vicinity of an insulator-metal transition (IMT) exhibits rich phenomenology and variety of interesting phases. A common avenue to induce IMTs in Mott insulators is doping, which inevitably leads to disorder. While disorder is well known to create electronic inhomogeneity, recent theoretical studies have indicated that it may play an unexpected and much more profound role in controlling the properties of Mott systems. Theory predicts that disorder might play a role in driving a Mott insulator across an IMT, with the emergent metallic state hosting a power law suppression of the density of states (with exponent close to 1; V-shaped gap) centered at the Fermi energy. Such V-shaped gaps have been observed in Mott systems but their origins are as yet unknown. To investigate this, we use scanning tunneling microscopy and spectroscopy to study isovalent Ru substitutions in Sr$_3$(Ir$_{1-x}$Ru$_x$)$_2$O$_7$ which drives the system into an antiferromagnetic, metallic state. Our experiments reveal that many core features of the IMT such as power law density of states, pinning of the Fermi energy with increasing disorder, and persistence of antiferromagnetism can be understood as universal features of a disordered Mott system near an IMT and suggest that V-shaped gaps may be an inevitable consequence of disorder in doped Mott insulators., Comment: 13 pages, 4 figures; A new version can be find in PNAS
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- 2018
169. Quantum oscillations with magnetic hysteresis observed in CeTe3 thin films
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Mori, Watanabe, Sanghyun, Lee, Takuya, Asano, Takashi, Ibe, Masashi, Tokuda, Hiroki, Taniguchi, Daichi, Ueta, Yoshinori, Okada, Kensuke, Kobayashi, Yasuhiro, Niimi, Mori, Watanabe, Sanghyun, Lee, Takuya, Asano, Takashi, Ibe, Masashi, Tokuda, Hiroki, Taniguchi, Daichi, Ueta, Yoshinori, Okada, Kensuke, Kobayashi, and Yasuhiro, Niimi
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We have performed magnetotransport measurements in CeTe3 thin films down to 0.2K. It is known that CeTe3 has two magnetic transitions at TN 1 approximate to 3K and TN 2 approximate to 1K. A clear Shubnikov-de-Haas (SdH) oscillation was observed at 4K, demonstrating the strong two-dimensional nature in this material. BelowTN 2, the SdH oscillation has two frequencies, indicating that the Fermi surface could be slightly modulated due to the second magnetic transition. We also observed a magnetic hysteresis in the SdH oscillation below TN 1. Specifically, there is a unique spike in the magnetoresistance at B approximate to 0.6T only when the magnetic field is swept from a high enough field (more than 2T) to zero field., source:https://aip.scitation.org/doi/10.1063/5.0007517
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- 2020
170. Positron emission tomography/computed tomography as a clinical diagnostic tool for anterior mediastinal tumors
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Takehiro Yamada, Ryoko Saito, Akira Sakurada, Yoshinori Okada, Yasuyuki Taki, Masafumi Noda, Ryoui Goto, Hideo Shimomura, Tatsushi Mutoh, Hirotsugu Notsuda, Yasushi Matsuda, and Tatsuaki Watanabe
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Adult ,Male ,medicine.medical_specialty ,Thymoma ,Adolescent ,Lymphoma ,Standardized uptake value ,Mediastinal Neoplasms ,Sensitivity and Specificity ,Diagnosis, Differential ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,Positron Emission Tomography Computed Tomography ,hemic and lymphatic diseases ,medicine ,Humans ,Stage (cooking) ,neoplasms ,Aged ,Aged, 80 and over ,PET-CT ,medicine.diagnostic_test ,business.industry ,Lymphoblastic lymphoma ,Mediastinum ,Teratoma ,MALT lymphoma ,General Medicine ,Middle Aged ,Neoplasms, Germ Cell and Embryonal ,medicine.disease ,Positron emission tomography ,030220 oncology & carcinogenesis ,Female ,030211 gastroenterology & hepatology ,Surgery ,Radiology ,Differential diagnosis ,business - Abstract
The purpose of this study was to assess the usefulness of positron emission tomography/computed tomography (PET/CT) in the differential diagnosis of anterior mediastinal tumors. A total of 94 patients with anterior mediastinal masses or nodules (male, n = 41; female, n = 53; age, 17–84 years) were retrospectively evaluated. All patients were evaluated by PET/CT and the masses or nodules were histologically diagnosed in our institution. Anterior mediastinal masses and nodules were classified into two disease categories: Low (thymic hyperplasia, thymoma, mature teratoma, and MALT lymphoma) and High (thymic carcinoid, thymic cancer, diffuse large B-cell lymphoma, T-cell lymphoblastic lymphoma, Hodgkin’s lymphoma, and malignant germ cell tumors) groups. The sensitivity and specificity of maximum standardized uptake value (SUVmax) 7.5 for the detection of High group were 77% and 100%, respectively. The SUVmax distributions of the WHO histological thymoma types and Masaoka stage thymomas extensively overlapped. Masaoka stage III thymomas had significantly higher SUVmax than Masaoka stage I thymomas. Regarding the TNM classification, the SUVmax of T3 and T1b thymomas was higher than T1a thymoma. Although the SUVmax of each disease overlapped, PET/CT findings provided useful information for the differential diagnosis of anterior mediastinal masses.
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- 2018
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171. Selenoprotein P Promotes the Development of Pulmonary Arterial Hypertension
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Yasushi Hoshikawa, Hiroaki Shimokawa, Nobuhiro Yaoita, Md. Elias-Al-Mamun, Kimio Satoh, Taijyu Satoh, Masamichi Nogi, Yoshiro Saito, Ryo Kurosawa, Nobuhiro Kikuchi, Yoshinori Okada, Junichi Omura, Satoshi Miyata, Shinichiro Sunamura, and Mohammad Abdul Hai Siddique
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0301 basic medicine ,medicine.medical_specialty ,business.industry ,Selenoprotein P ,030204 cardiovascular system & hematology ,Hypoxia (medical) ,Mitochondrion ,medicine.disease ,medicine.disease_cause ,Pulmonary hypertension ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,Smooth muscle ,Apoptosis ,Physiology (medical) ,Internal medicine ,medicine.artery ,Pulmonary artery ,medicine ,Cardiology ,medicine.symptom ,Cardiology and Cardiovascular Medicine ,business ,Oxidative stress - Abstract
Background: Excessive proliferation and apoptosis resistance of pulmonary artery smooth muscle cells (PASMCs) are key mechanisms of pulmonary arterial hypertension (PAH). Despite the multiple combination therapy, a considerable number of patients develop severe pulmonary hypertension (PH) because of the lack of diagnostic biomarker and antiproliferative therapies for PASMCs. Methods: Microarray analyses were used to identify a novel therapeutic target for PAH. In vitro experiments, including lung and serum samples from patients with PAH, cultured PAH-PASMCs, and high-throughput screening of 3336 low-molecular-weight compounds, were used for mechanistic study and exploring a novel therapeutic agent. Five genetically modified mouse strains, including PASMC-specific selenoprotein P (SeP) knockout mice and PH model rats, were used to study the role of SeP and therapeutic capacity of the compounds for the development of PH in vivo. Results: Microarray analysis revealed a 32-fold increase in SeP in PAH-PASMCs compared with control PASMCs. SeP is a widely expressed extracellular protein maintaining cellular metabolism. Immunoreactivity of SeP was enhanced in the thickened media of pulmonary arteries in PAH. Serum SeP levels were also elevated in patients with PH compared with controls, and high serum SeP predicted poor outcome. SeP-knockout mice ( SeP –/– ) exposed to chronic hypoxia showed significantly reduced right ventricular systolic pressure, right ventricular hypertrophy, and pulmonary artery remodeling compared with controls. In contrast, systemic SeP-overexpressing mice showed exacerbation of hypoxia-induced PH. Furthermore, PASMC-specific SeP –/– mice showed reduced hypoxia-induced PH compared with controls, whereas neither liver-specific SeP knockout nor liver-specific SeP-overexpressing mice showed significant differences with controls. Altogether, protein levels of SeP in the lungs were associated with the development of PH. Mechanistic experiments demonstrated that SeP promotes PASMC proliferation and resistance to apoptosis through increased oxidative stress and mitochondrial dysfunction, which were associated with activated hypoxia-inducible factor-1α and dysregulated glutathione metabolism. It is important to note that the high-throughput screening of 3336 compounds identified that sanguinarine, a plant alkaloid with antiproliferative effects, reduced SeP expression and proliferation in PASMCs and ameliorated PH in mice and rats. Conclusions: These results indicate that SeP promotes the development of PH, suggesting that it is a novel biomarker and therapeutic target of the disorder.
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- 2018
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172. Periostin is a negative prognostic factor and promotes cancer cell proliferation in non-small cell lung cancer
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Jiro Abe, Mai Mochizuki, Keiichi Tamai, Kazunori Yamaguchi, Rie Shibuya, Toshimasa Okazaki, Satomi Takahashi, Kennichi Satoh, Mao Nakamura, Ikuro Sato, Akira Kudo, and Yoshinori Okada
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0301 basic medicine ,periostin ,Cell growth ,business.industry ,Matricellular protein ,Cancer ,Periostin ,medicine.disease ,03 medical and health sciences ,lung cancer ,030104 developmental biology ,0302 clinical medicine ,cell proliferation ,Oncology ,Cancer stem cell ,Tumor progression ,030220 oncology & carcinogenesis ,Cancer research ,Carcinoma ,medicine ,prognosis ,Lung cancer ,business ,prognostic factor ,Research Paper - Abstract
// Toshimasa Okazaki 1, 3, 6 , Keiichi Tamai 1 , Rie Shibuya 1 , Mao Nakamura 2 , Mai Mochizuki 1 , Kazunori Yamaguchi 2 , Jiro Abe 3 , Satomi Takahashi 3 , Ikuro Sato 4 , Akira Kudo 5 , Yoshinori Okada 6 and Kennichi Satoh 1 1 Division of Cancer Stem Cell, Miyagi Cancer Center Research Institute, Natori, Japan 2 Division of Molecular and Cellular Oncology, Miyagi Cancer Center Research Institute, Natori, Japan 3 Department of Thoracic Surgery, Miyagi Cancer Center, Natori, Japan 4 Department of Pathology, Miyagi Cancer Center, Natori, Japan 5 Department of Biological Information, Tokyo Institute of Technology, Yokohama, Japan 6 Department of Thoracic Surgery, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Japan Correspondence to: Keiichi Tamai, email: tamaikeiichi@med.tohoku.ac.jp Keywords: periostin; lung cancer; cell proliferation; prognostic factor; prognosis Received: December 12, 2017 Accepted: April 28, 2018 Published: July 27, 2018 ABSTRACT Periostin is a matricellular protein that is secreted by fibroblasts and interacts with various cell-surface integrin molecules. Although periostin is known to support tumor development in human malignancies, little is known about its effect on lung-cancer progression. We here demonstrate that periostin is a negative prognostic factor that increases tumor proliferation through ERK signaling in non-small cell lung carcinoma. We classified 189 clinical specimens from patients with non-small cell lung-cancer according to high or low periostin expression, and found a better prognosis for patients with low rather than high periostin, even in cases of advanced-stage cancer. In a syngenic implantation model, murine Ex3LL lung-cancer cells formed smaller tumor nodules in periostin −/− mice than in periostin +/+ mice, both at the primary site and at metastatic lung sites. An in vitro proliferation assay showed that stimulation with recombinant periostin increased Ex3LL-cell proliferation. We also found that periostin promotes ERK phosphorylation, but not Akt or FAK activation. These findings suggest that periostin represents a potential target in lung-cancer tumor progression.
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- 2018
173. Epidermal Growth Factor Receptor Mutation as a Risk Factor for Recurrence in Lung Adenocarcinoma
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Makoto Endoh, Motoyasu Sagawa, Satoshi Shiono, Naoki Yanagawa, Satomi Takahashi, Yuki Matsumura, Kazuki Hayasaka, Yoshinori Okada, Hiroyuki Suzuki, Akira Sakurada, Jiro Abe, and Masato Katahira
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Male ,0301 basic medicine ,Pulmonary and Respiratory Medicine ,medicine.medical_specialty ,Lung Neoplasms ,Adenocarcinoma of Lung ,Kaplan-Meier Estimate ,Gastroenterology ,Cohort Studies ,03 medical and health sciences ,0302 clinical medicine ,Risk Factors ,Internal medicine ,medicine ,Humans ,Neoplasm Invasiveness ,Epidermal growth factor receptor ,Risk factor ,Pneumonectomy ,Survival analysis ,Aged ,Neoplasm Staging ,Proportional Hazards Models ,Retrospective Studies ,Lung ,biology ,business.industry ,Proportional hazards model ,Incidence (epidemiology) ,Retrospective cohort study ,Middle Aged ,Prognosis ,medicine.disease ,Survival Analysis ,ErbB Receptors ,Gene Expression Regulation, Neoplastic ,030104 developmental biology ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,Mutation ,biology.protein ,Adenocarcinoma ,Female ,Surgery ,Neoplasm Recurrence, Local ,Cardiology and Cardiovascular Medicine ,business - Abstract
The presence of epidermal growth factor receptor (EGFR) mutations is an established prognostic factor for patients with advanced lung adenocarcinoma. Here, we examined whether EGFR mutation status is a prognostic factor for patients who had undergone surgery.Clinicopathologic data from 1,463 patients who underwent complete surgical resection for lung adenocarcinoma between 2005 and 2012 were collected. Differences in postoperative recurrence-free survival and overall survival according to EGFR mutation status were evaluated.Of 835 eligible patients, the numbers of patients with wild-type EGFR (WT), exon 19 deletion (Ex19), and exon 21 L858R (Ex21) were 426, 175, and 234, respectively. Patients with Ex19 had a significantly higher incidence of extrathoracic recurrence than patients with Ex21 (p = 0.004). The 5-year recurrence-free survival rates for patients with WT, Ex19, and Ex21 were 63.0%, 67.5%, and 78.2%, respectively. The Ex21 group had a significantly longer recurrence-free survival than the WT group (p0.001) and the Ex19 group (p = 0.016). The 5-year overall survival for patients with WT, Ex19, and Ex21 were 76.9%, 86.5%, and 87.5%, respectively. Patients with Ex19 and Ex21 had a significantly longer overall survival than patients with WT (Ex19, p = 0.009; Ex21, p0.001). Multivariate analysis for recurrence-free survival showed that Ex19 was significantly associated with a worse prognosis than Ex21 (p = 0.019).Patients with Ex19 had significantly shorter recurrence-free survival and had extrathoracic recurrence more frequently than patients with Ex21 among patients with resected lung adenocarcinoma, implying that Ex19 could be a worse prognostic factor.
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- 2018
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174. Single lung transplantation for lymphangioleiomyomatosis: a single-center experience in Japan
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Takashi Kondo, Yoshinori Okada, Yoshikatsu Saiki, Yasushi Matsuda, Masafumi Noda, Yutaka Ejima, Hisashi Oishi, Tatsuaki Watanabe, and Kuniaki Seyama
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Adult ,Male ,medicine.medical_specialty ,Lung Neoplasms ,genetic structures ,medicine.medical_treatment ,Single Center ,Young Adult ,03 medical and health sciences ,Postoperative Complications ,0302 clinical medicine ,Japan ,immune system diseases ,hemic and lymphatic diseases ,medicine ,Humans ,Lung transplantation ,Lymphangioleiomyomatosis ,030212 general & internal medicine ,Survival rate ,Pleurodesis ,business.industry ,Pneumothorax ,Chylothorax ,General Medicine ,Middle Aged ,bacterial infections and mycoses ,medicine.disease ,Surgery ,Pleural Effusion ,Survival Rate ,Treatment Outcome ,030228 respiratory system ,Female ,lipids (amino acids, peptides, and proteins) ,Intubation ,Complication ,business ,Lung Transplantation - Abstract
Lung transplantation is accepted as an effective modality for patients with end-stage pulmonary lymphangioleiomyomatosis (LAM). Generally, bilateral lung transplantation is preferred to single lung transplantation (SLT) for LAM because of native lung-related complications, such as pneumothorax and chylothorax. It remains controversial whether SLT is a suitable surgical option for LAM. The objective of this study was to evaluate the morbidity, mortality and outcome after SLT for LAM in a lung transplant center in Japan. We reviewed the records of 29 patients who underwent SLT for LAM in our hospital between March, 2000 and November, 2017. The data collected included the pre-transplant demographics of recipients, surgical characteristics, complications, morbidity, mortality and survival after SLT for LAM. The most common complication after SLT for LAM was contralateral pneumothorax (n = 7; 24.1%). Six of these recipients were treated successfully with chest-tube placement and none required surgery for the pneumothorax. The second-most common complication was chylous pleural effusion (n = 6; 20.7%) and these recipients were all successfully treated by pleurodesis. The 5-year survival rate after SLT for LAM was 79.5%. LAM-related complications after SLT for this disease can be managed. SLT is a treatment option and may improve access to lung transplantation for patients with end-stage LAM.
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- 2018
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175. Anisotropic band splitting in monolayer NbSe2: implications for superconductivity and charge density wave
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Yuki Nakata, Shuji Hasegawa, Takashi Takahashi, Takashi Koretsune, Keiji Ueno, Katsuaki Sugawara, Taro Hitosugi, Takafumi Sato, Yoshinori Okada, and Satoru Ichinokura
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Materials science ,02 engineering and technology ,01 natural sciences ,law.invention ,lcsh:Chemistry ,Condensed Matter::Materials Science ,law ,Condensed Matter::Superconductivity ,0103 physical sciences ,Monolayer ,lcsh:TA401-492 ,General Materials Science ,Symmetry breaking ,010306 general physics ,Electronic band structure ,Superconductivity ,Condensed matter physics ,Mechanical Engineering ,General Chemistry ,021001 nanoscience & nanotechnology ,Condensed Matter Physics ,Brillouin zone ,lcsh:QD1-999 ,Mechanics of Materials ,lcsh:Materials of engineering and construction. Mechanics of materials ,Scanning tunneling microscope ,0210 nano-technology ,Bilayer graphene ,Charge density wave - Abstract
Realization of unconventional physical properties in two-dimensional (2D) transition-metal dichalcogenides (TMDs) is currently one of the key challenges in condensed-matter systems. However, the electronic properties of 2D TMDs remain largely unexplored compared to those of their bulk counterparts. Here, we report the fabrication of a high-quality monolayer NbSe2 film with a trigonal prismatic structure by molecular beam epitaxy, and the study of its electronic properties by scanning tunneling microscopy, angle-resolved photoemission spectroscopy, and electrical transport measurements, together with first-principles band-structure calculations. In addition to a charge density wave (CDW) with 3 × 3 periodicity and superconductivity below 1.5 K, we observed sizable (~0.1 eV) band splitting along the Γ-K cut in the Brillouin zone due to inversion symmetry breaking in the monolayer crystal. This splitting is highly anisotropic in k space, leading to a spin-split van-Hove singularity in the band structure. The present results suggest the importance of spin–orbit coupling and symmetry breaking for unconventional superconductivity and CDW properties in monolayer TMDs. The interplay between symmetry breaking, superconductivity and charge density wave in monolayer NbSe2 is unveiled by spectroscopic techniques. A team led by Takafumi Sato at Tohoku University used molecular beam epitaxy to fabricate atomically thin NbSe2 films on bilayer graphene, and investigated their electronic properties by a combination of electrical transport measurements, scanning tunneling microscopy, and angle-resolved photoemission spectroscopy. A charge density wave transition with a strong periodic charge modulation was detected below 1.5 K, accompanied by the emergence of superconductivity. Owing to the inversion symmetry breaking occurring in monolayer NbSe2, a band splitting developed along the Γ-Κ direction of the Brillouin zone. Such band splitting was found to be related to the robustness of the observed superconductivity, as well as the formation of the charge density wave.
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- 2018
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176. Endobronchial Topical Amphotericin B Instillation for Pulmonary Chromomycosis After Lung Transplantation: A Case Report
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Yoshinori Okada, S. Maeda, Akira Sakurada, T. Amemiya, Y. Yoshida, Tatsuaki Watanabe, Hideki Mitomo, Hisashi Oishi, Katsuhiko Kamei, Toshiaki Kikuchi, Hirotsugu Notsuda, Yasuhiro H. Matsuda, Tetsu Sado, Hiromichi Niikawa, and Masafumi Noda
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medicine.medical_specialty ,Antifungal Agents ,Itraconazole ,Administration, Topical ,medicine.medical_treatment ,Idiopathic Pulmonary Hypertension ,030230 surgery ,03 medical and health sciences ,Postoperative Complications ,0302 clinical medicine ,Amphotericin B ,Bronchoscopy ,medicine ,Humans ,Lung transplantation ,Scedosporium ,Lung ,Voriconazole ,Transplantation ,Bronchus ,Chromoblastomycosis ,Lung Diseases, Fungal ,Scedosporium prolificans ,biology ,business.industry ,Middle Aged ,respiratory system ,biology.organism_classification ,respiratory tract diseases ,Surgery ,medicine.anatomical_structure ,Female ,030211 gastroenterology & hepatology ,business ,Lung Transplantation ,medicine.drug - Abstract
We report a very rare case of pulmonary chromomycosis caused by Scedosporium prolificans that developed after lung transplantation and was successfully treated with endobronchial topical amphotericin B instillation. The subject was a woman in her 50s with a history of bilateral lobar lung transplantation from living donors for idiopathic pulmonary hypertension. Eight years after the lung transplantation, chest radiography X-ray and computed tomography showed an abnormal shadow in the right lung. Bronchoscopic findings showed obstruction by a fungal component at the laterobasal bronchus B9. She was diagnosed with pulmonary chromomycosis after S. prolificans was detected in the bronchial aspirate. Systemic antifungal treatment with itraconazole was ineffective. Therefore, we administered topical amphotericin B weekly via endobronchial instillation and replaced oral itraconazole with voriconazole. The endobronchial procedure was safe and tolerable. Bronchial obstruction improved after three 3 instillations. We continued topical amphotericin B instillation once every 3 months for 2 years, and the abnormal shadow nearly disappeared. This case report describes infection by S. prolificans, which rarely becomes an etiologic agent in lung transplant patients, and shows that endobronchial topical amphotericin B instillation is a therapeutic option when systemic antifungal treatment is ineffective.
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- 2018
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177. Comparison of PETINIA and LC-MS/MS for determining plasma mycophenolic acid concentrations in Japanese lung transplant recipients
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Hiroaki Yamaguchi, Yasushi Matsuda, Shinya Takasaki, Nariyasu Mano, Masafumi Kikuchi, Miki Akiba, Kanehiko Hisamichi, Masafumi Noda, Yoshinori Okada, Masaki Tanaka, and Akiko Takahashi
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medicine.medical_specialty ,Urology ,Short Report ,lcsh:RS1-441 ,Pharmacology (nursing) ,Turbidimetric inhibition immunoassay ,030226 pharmacology & pharmacy ,01 natural sciences ,Mycophenolic acid ,Mycophenolic acid acyl glucuronide ,lcsh:Pharmacy and materia medica ,03 medical and health sciences ,0302 clinical medicine ,Liquid chromatography–mass spectrometry ,Lc ms ms ,PETINIA ,medicine ,Pharmacology (medical) ,LC-MS/MS ,Lung ,medicine.diagnostic_test ,business.industry ,010401 analytical chemistry ,lcsh:RM1-950 ,Positive bias ,Confidence interval ,0104 chemical sciences ,medicine.anatomical_structure ,lcsh:Therapeutics. Pharmacology ,Therapeutic drug monitoring ,Japanese ,business ,medicine.drug ,Lung transplant - Abstract
Background Mycophenolic acid (MPA) treatment requires therapeutic drug monitoring to improve the outcome after organ transplantation. The aim of this study was to compare two methods, a particle enhanced turbidimetric inhibition immunoassay (PETINIA) and a reference liquid chromatography tandem mass spectrometry (LC-MS/MS) for determining plasma MPA concentrations from Japanese lung transplant recipients. Methods Plasma MPA concentrations were determined from 20 Japanese lung transplant recipients using LC-MS/MS and the PETINIA on the Dimension Xpand Plus-HM analyzer. Results The mean MPA concentration measured by PETINIA was significantly higher than that measured by LC-MS/MS (3.26 ± 2.73 μg/mL versus 2.82 ± 2.71 μg/mL, P
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178. Bone marrow mesenchymal stromal cells protect allograft lung transplants from acute rejection via the PD-L1/IL-17A axis
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Akira Sakurada, Masafumi Noda, Tatsuaki Watanabe, Yoshinori Okada, Yasushi Hoshikawa, Masahiko Kanehira, Hirotsugu Notsuda, Yui Watanabe, Shinya Ohkouchi, Takashi Kondo, and Naoya Ishibashi
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Graft Rejection ,Male ,0301 basic medicine ,Pathology ,medicine.medical_specialty ,T-Lymphocytes ,T cell ,Down-Regulation ,Gene Expression ,Bone Marrow Cells ,B7-H1 Antigen ,Proinflammatory cytokine ,03 medical and health sciences ,0302 clinical medicine ,Downregulation and upregulation ,PD-L1 ,medicine ,Animals ,RNA, Messenger ,Lung ,biology ,business.industry ,Interleukin-17 ,Mesenchymal stem cell ,Mesenchymal Stem Cells ,General Medicine ,Allografts ,Rats ,Transplantation ,surgical procedures, operative ,030104 developmental biology ,medicine.anatomical_structure ,Rats, Inbred Lew ,Acute Disease ,Models, Animal ,biology.protein ,Surgery ,Bone marrow ,business ,Lung Transplantation ,030215 immunology - Abstract
Using a rat model of allograft lung transplantation, we investigated the effectiveness of mesenchymal stromal cells (MSCs) as prophylactic and therapeutic agents against the acute rejection of lung grafts. Lung grafts were harvested from donor rats and transplanted orthotopically into major histocompatibility complex-mismatched rats. MSCs were administered to the recipients once (on day 0) or twice (on days 0 and 3) after transplantation. The grade of acute rejection was evaluated both macroscopically and microscopically 6 days after transplantation. To elucidate the related mechanism, mRNA levels of inflammatory cytokines and immunomodulatory receptors in the transplanted grafts were measured using quantitative RT-PCR. The lung graft tissue from the rats that received MSCs post-surgically was protected from acute rejection significantly better than that from the untreated controls. Notably, the rats administered MSCs twice after surgery exhibited the least signs of rejection, with a markedly upregulated mRNA level of PD-L1 and a downregulated mRNA level of IL-17A. This study assessed MSC protection of lung allografts from acute rejection by modulating T cell activity via enforced expression of PD-L1 in transplants and downregulation of IL-17A.
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- 2018
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179. Oxidative stress enhances the expression of IL-33 in human airway epithelial cells
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Yoshinori Okada, Hiroyuki Aizawa, Masafumi Noda, Yutaka Shishikura, Tomohiro Ichikawa, Mitsuhiro Yamada, Naoya Fujino, Masakazu Ichinose, Mutsuo Yamaya, Akira Koarai, Satoru Yanagisawa, Hisatoshi Sugiura, and Tadahisa Numakura
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Male ,0301 basic medicine ,MAPK/ERK pathway ,Rhinovirus ,Cell Survival ,MAP Kinase Signaling System ,medicine.medical_treatment ,Gene Expression ,Stimulation ,Respiratory Mucosa ,medicine.disease_cause ,Antiviral Agents ,Pathogenesis ,03 medical and health sciences ,0302 clinical medicine ,Cell Line, Tumor ,medicine ,Humans ,COPD ,Protein kinase A ,Aged ,lcsh:RC705-779 ,Dose-Response Relationship, Drug ,business.industry ,Research ,Correction ,Exacerbation ,Hydrogen Peroxide ,lcsh:Diseases of the respiratory system ,Middle Aged ,Interleukin-33 ,medicine.disease ,respiratory tract diseases ,Interleukin 33 ,Poly I-C ,030104 developmental biology ,Cytokine ,030228 respiratory system ,Oxidative stress ,Viral infection ,Cancer research ,IL-33 ,Female ,business - Abstract
Background Interleukin-33 (IL-33) is a cytokine belonging to the IL-1 family, and its possible involvement in the pathophysiology of COPD and viral-induced exacerbations has been demonstrated. IL-33 has been shown to be increased in the airway epithelial cells from COPD patients, but the regulating mechanism of IL-33 expression in airway epithelial cells remains largely unknown. In the current study, we examined whether oxidative stress, which participates in the pathogenesis of COPD, affects the expression of IL-33 in airway epithelial cells and also evaluated the effect during viral infection. Methods The involvement of oxidative stress in the expression of IL-33, and its signal pathway was examined after stimulation with hydrogen peroxide (H2O2), with or without stimulation by polyinosinic-polycytidylic acid [poly (I:C)], a synthetic analogue of dsRNA that mimics viral infection, or rhinovirus infection in NCI-H292 cells and primary human bronchial epithelial cells (HBECs). In addition, the effect of antioxidant, N-acetylcysteine (NAC) in the expression of IL-33 was compared between HBECs from healthy subjects and those from COPD patients. Results Treatment with H2O2 significantly potentiated IL-33 expression in NCI-H292 cells, and the potentiation was reversed by NAC treatment. Mitogen-activated protein kinase (MAPK) inhibitors, but not nuclear factor-kappa B inhibitors, also significantly decreased the H2O2-potentiated IL-33 expression. In addition, H2O2 significantly potentiated the poly (I:C)- or rhinovirus-stimulated IL-33 expression. In HBECs from healthy subjects, H2O2-potentiated IL-33 expression and its reversal by NAC was also confirmed. Under the condition without H2O2-stimulation, treatment with NAC significantly decreased the expression of IL-33 in HBECs from COPD patients, but not in those from healthy subjects. Conclusions These results demonstrate that oxidative stress involves in the expression of IL-33 in airway epithelial cells via MAPK signal pathway and it augments IL-33 expression during viral infection. This mechanism may participate in the regulation of IL-33 expression in airway epithelial cells in COPD and the viral-induced exacerbations. Modulation of this pathway could become a therapeutic target for viral-induced exacerbations of COPD. Electronic supplementary material The online version of this article (10.1186/s12931-018-0752-9) contains supplementary material, which is available to authorized users.
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- 2018
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180. Atomic-scale visualization of oxide thin-film surfaces
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Yoshinori Okada, Ryota Shimizu, Takeo Ohsawa, Taro Hitosugi, and Katsuya Iwaya
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Complex oxide ,Materials science ,lcsh:Biotechnology ,306 Thin film / Coatings ,Oxide ,02 engineering and technology ,212 Surface and interfaces ,01 natural sciences ,Atomic units ,Pulsed laser deposition ,law.invention ,Condensed Matter::Materials Science ,chemistry.chemical_compound ,law ,10 Engineering and Structural materials ,lcsh:TP248.13-248.65 ,0103 physical sciences ,lcsh:TA401-492 ,General Materials Science ,205 Catalyst / Photocatalyst / Photosynthesis ,105 Low-Dimension (1D/2D) materials ,Physics::Chemical Physics ,Thin film ,010306 general physics ,pulsed laser deposition ,business.industry ,Focus on New Materials Science and Element Strategy ,Heterojunction ,Condensed Matter::Mesoscopic Systems and Quantum Hall Effect ,021001 nanoscience & nanotechnology ,Visualization ,201 Electronics / Semiconductor / TCOs ,chemistry ,Optoelectronics ,scanning tunneling microscopy ,lcsh:Materials of engineering and construction. Mechanics of materials ,Scanning tunneling microscope ,0210 nano-technology ,business ,Oxide thin films - Abstract
The interfaces of complex oxide heterostructures exhibit intriguing phenomena not observed in their constituent materials. The oxide thin-film growth of such heterostructures has been successfully controlled with unit-cell precision; however, atomic-scale understandings of oxide thin-film surfaces and interfaces have remained insufficient. We examined, with atomic precision, the surface and electronic structures of oxide thin films and their growth processes using low-temperature scanning tunneling microscopy. Our results reveal that oxide thin-film surface structures are complicated in contrast to the general perception and that atomically ordered surfaces can be achieved with careful attention to the surface preparation. Such atomically ordered oxide thin-film surfaces offer great opportunities not only for investigating the microscopic origins of interfacial phenomena but also for exploring new surface phenomena and for studying the electronic states of complex oxides that are inaccessible using bulk samples.
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- 2018
181. Inflammation and PD-L1 expression in pulmonary neuroendocrine tumors
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Günter Klöppel, Katja Steiger, Ayaka J. Iwata, Akira Sakurada, Naomi Oka, Hirotaka Ishida, Atsuko Kasajima, Hiroyoshi Suzuki, Hironobu Sasano, Wilko Weichert, Yoshinori Okada, Yuichi Ishikawa, Toru Kameya, and Björn Konukiewitz
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Male ,0301 basic medicine ,Cancer Research ,Lung Neoplasms ,Endocrinology, Diabetes and Metabolism ,Cell ,Inflammation ,Kaplan-Meier Estimate ,CD8-Positive T-Lymphocytes ,Neuroendocrine tumors ,B7-H1 Antigen ,03 medical and health sciences ,0302 clinical medicine ,Endocrinology ,Immune system ,PD-L1 ,medicine ,Humans ,Lung cancer ,Aged ,Lung ,biology ,business.industry ,Middle Aged ,medicine.disease ,Neuroendocrine Tumors ,030104 developmental biology ,medicine.anatomical_structure ,Oncology ,030220 oncology & carcinogenesis ,biology.protein ,Cancer research ,Female ,medicine.symptom ,business ,CD8 - Abstract
In the light of novel cancer immune therapies, the status of antitumor inflammatory response and its regulation has gained much attention in patients with lung cancer. Ample datasets exist for non-small-cell lung cancer, but those for pulmonary neuroendocrine tumors are scarce and controversial. Here, tumor-associated inflammation, CD8+ cell infiltration and PD-L1 status were evaluated in a cohort of 57 resected carcinoids and 185 resected neuroendocrine carcinomas of the lung (58 large cell carcinomas and 127 small cell carcinomas). Data were correlated with clinicopathological factors and survival. Moderate or high tumor-associated inflammation was detected in 4 carcinoids (7%) and in 37 neuroendocrine carcinomas (20%). PD-L1 immunoreactivity was seen in immune cells of 73 (39%) neuroendocrine carcinomas, while tumor cells were labeled in 21 (11%) cases. Inflammatory cells and tumor cells in carcinoids lacked any PD-L1 expression. In neuroendocrine carcinomas, PD-L1 positivity in immune cells, but not in tumor cells, was associated with intratumoral CD8+ cell infiltration (P P P P
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- 2018
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182. Correction to: Risk assessments for broncho-pleural fistula and respiratory failure after lung cancer surgery by National Clinical Database Japan
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Masami Sato, Masayuki Chida, Morihito Okada, Yoshihisa Shimada, Takashi Kondo, Shinichi Toyooka, Yukio Sato, Norihiko Ikeda, Shunsuke Endo, Ichiro Yoshino, Haruhiko Kondo, Jun Nakajima, Hiroaki Miyata, Yoshinori Okada, Meinoshin Okumura, and Eriko Fukuchi
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Pulmonary and Respiratory Medicine ,medicine.medical_specialty ,Lung cancer surgery ,Respiratory failure ,business.industry ,Medicine ,Surgery ,General Medicine ,Pleural fistula ,Cardiology and Cardiovascular Medicine ,business ,Risk assessment - Published
- 2019
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183. A prospective 5-year follow-up study after limited resection for lung cancer with ground-glass opacity
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Tohru Hasumi, Hidetaka Uramoto, Motoyasu Sagawa, Nobuyuki Sato, Satoshi Shiono, Hiroyuki Deguchi, Katsuo Usuda, Yoshinori Okada, Hiroyuki Oizumi, Jotaro Shibuya, Akira Sakurada, Hiroyuki Suzuki, Jiro Abe, Masayuki Chida, and Masami Sato
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Adult ,Male ,Pulmonary and Respiratory Medicine ,Surgical margin ,medicine.medical_specialty ,Lung Neoplasms ,Adenocarcinoma ,030204 cardiovascular system & hematology ,Disease-Free Survival ,Ground-glass opacity ,Pulmonary function testing ,03 medical and health sciences ,0302 clinical medicine ,medicine ,Carcinoma ,Humans ,Prospective Studies ,Lung cancer ,Lung ,Survival rate ,Aged ,business.industry ,General Medicine ,Adenocarcinoma, Bronchiolo-Alveolar ,Middle Aged ,medicine.disease ,Survival Analysis ,Editorial ,030220 oncology & carcinogenesis ,Female ,Surgery ,Radiology ,medicine.symptom ,Cardiology and Cardiovascular Medicine ,business ,Follow-Up Studies ,Wedge resection (lung) - Abstract
Objectives The incidence of small-sized pulmonary adenocarcinomas with ground-glass opacity (GGO) has recently increased, with excellent postoperative prognosis. The limited resection of such cancers has been deemed to be acceptable based on retrospective studies. We conducted a prospective multi-institutional study evaluating the validity of limited resection for small-sized pulmonary adenocarcinoma with GGO. Methods The inclusion criteria were 25-80 years of age, no prior treatment, a maximum tumour diameter of 8-20 mm, a GGO ratio of ≥ 80%, clinical T1N0M0, lower 18F-fluorodeoxyglucose accumulation than the mediastinum, resectable by sublobar resection, pulmonary lobectomy tolerable and an intraoperative pathological diagnosis of bronchiloalveolar carcinoma. Wedge resection was preferred, but segmentectomy was permitted. Disease-specific survival and overall survival were analysed. Results From November 2006 to April 2012, 73 patients were enrolled from 13 institutions. One patient was ineligible, and the remaining 72 patients were preregistered. The tumours of 3 and 14 patients were intraoperatively diagnosed as benign lesions and adenocarcinomas with mixed subtype, respectively. Intraoperative cytological/histological examination of surgical margin was not performed in 2 patients, and the remaining 53 patients were ultimately eligible for this study. The mean tumour size was 14.0 mm and the mean GGO ratio was 95.9%. Thirty-nine and 14 patients underwent wedge resection and segmentectomy, respectively. Although all tumours were intraoperatively diagnosed as bronchioloalveolar carcinomas, 6 were ultimately diagnosed as adenocarcinoma with a mixed subtype. No completion lobectomy was performed. As of 1 May 2017, no recurrence of the original lung cancer was observed during 60.0-126.3 months after surgery. Two patients died from other diseases. The 5-year disease-specific and overall survival rates were 100% and 98.1%, respectively. The reduction in the pulmonary function after limited resection was minimal. Conclusions With these criteria, limited resection was performed safely without any recurrence, and the postoperative pulmonary function was well preserved. The outcomes of limited resection for small-sized lung cancer with GGOs that met the criteria of this study were satisfactory.
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- 2017
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184. Development of a Liquid Chromatography–Tandem Mass Spectrometric Method for Quantification of Mycophenolic Acid and Its Glucuronides in Dried Blood Spot Samples
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Nariyasu Mano, Yasushi Matsuda, Masaki Tanaka, Akiko Takahashi, Hiromasa Iboshi, Hiroaki Yamaguchi, Yoshinori Okada, Shinya Takasaki, Masamitsu Maekawa, Hiroyuki Suzuki, Masafumi Kikuchi, and Miki Shimada
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Blood level ,Drug ,media_common.quotation_subject ,Tandem mass spectrometry ,Sensitivity and Specificity ,030226 pharmacology & pharmacy ,01 natural sciences ,Mycophenolic acid ,03 medical and health sciences ,Glucuronides ,0302 clinical medicine ,Tandem Mass Spectrometry ,medicine ,Humans ,Pharmacology (medical) ,Adverse effect ,media_common ,Pharmacology ,Antibiotics, Antineoplastic ,Chromatography ,medicine.diagnostic_test ,Chemistry ,010401 analytical chemistry ,Mycophenolic Acid ,Mass spectrometric ,0104 chemical sciences ,Dried blood spot ,Therapeutic drug monitoring ,Chromatography, Liquid ,medicine.drug - Abstract
Personalized immunosuppressive therapy, including accurate drug dosing based on the drug blood level, leads to better clinical outcomes, specifically regarding avoidance of drug-induced adverse effects and maintenance of efficacy. Mycophenolic acid (MPA) is used as an immunosuppressant in transplantation of various solid organs. The aim of this study was to develop a method for quantification of MPA and its metabolites, mycophenolic acid 7-O-glucuronide (MPAG) and mycophenolic acid acyl glucuronide, in dried blood spot (DBS) samples, using liquid chromatography/electrospray ionization/tandem mass spectrometry.For sample preparation, a microwave-drying approach was used to deactivate enzymes and reduce drying time. Blood volume was calculated in a DBS disk of 3 mm diameter. Concentrations of analytes in plasma from patients receiving mycophenolate mofetil were compared with DBS samples after hematocrit correction.The method yielded good recoveries of all 3 analytes (90.3%-104.2%). Blood volume in the disk was calculated as 3.0 ± 0.2 μL. Linearity over concentration ranges of 0.1-30 mcg/mL MPA, 0.1-200 mcg/mL MPAG, and 0.125-10 mcg/mL mycophenolic acid acyl glucuronide was obtained with r ≥0.999. Intraday and interday variations were less than 14.6%, and accuracy was within ±11.9%. Passing-Bablok analysis showed no significant differences between plasma concentrations and DBS concentrations after hematocrit correction of MPA and MPAG.We developed and validated a liquid chromatography/electrospray ionization-tandem mass spectrometry method for analysis of MPA in DBS samples. The method is useful for monitoring the MPA blood level.
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- 2017
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185. P08.09 Optimal Follow Up Care for Patients with P-stage I Non-Small Cell Lung Cancer After Surgical Treatment
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Akira Sakurada, Yoshinori Okada, Hisashi Oishi, Yui Watanabe, T. Suzuki, S. Eba, Hirotsugu Notsuda, R. Tanaka, and H. Oshio
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Pulmonary and Respiratory Medicine ,medicine.medical_specialty ,Stage I Non-Small Cell Lung Cancer ,Oncology ,business.industry ,Medicine ,Surgical treatment ,business ,Follow up care ,Surgery - Published
- 2021
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186. ラニナミビルオクタン酸エステル水和物の吸入に対する薬剤性ARDSが疑われたインフルエンザ関連脳症の1例(Influenza–associated encephalopathy complicated by laninamivir inhalation–associated anaphylaxis and drug induced acute respiratory distress syndrome: a case report)
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(Yusuke Okazaki), 岡崎 裕介, primary, (Itsuo Nakagawa), 中川 五男, additional, (Yoshinori Okada), 岡田 泰典, additional, and (Syozo Hidaka), 日高 昌三, additional
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- 2020
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187. The Efficacy of a Genetic Analysis of the BMPR2 Gene in a Patient with Severe Pulmonary Arterial Hypertension and an Atrial Septal Defect Treated with Bilateral Lung Transplantation
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Koji Fukuda, Saori Yamamoto, Norifumi Nakanishi, Yoshinori Okada, Hiroaki Shimokawa, Koichiro Sugimura, Hiroko Morisaki, Haruka Sato, Shunsuke Tatebe, Tatsuo Aoki, Kimio Satoh, Yoshikatsu Saiki, Hideaki Suzuki, Ryoko Saito, Ryo Konno, Osamu Adachi, Kotaro Oyama, Katsuya Kozu, and Nobuhiro Yaoita
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Adult ,Heart Defects, Congenital ,Male ,medicine.medical_specialty ,BMPR2 mutation ,Heart disease ,medicine.medical_treatment ,Hypertension, Pulmonary ,Septum secundum ,Case Report ,030204 cardiovascular system & hematology ,Bone Morphogenetic Protein Receptors, Type II ,Genetic analysis ,Severity of Illness Index ,Heart Septal Defects, Atrial ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,pulmonary arterial hypertension ,Internal Medicine ,medicine ,lung transplantation ,Lung transplantation ,Humans ,Familial Primary Pulmonary Hypertension ,atrial septal defect ,Genetic Testing ,business.industry ,Bilateral lung transplantation ,Eisenmenger syndrome ,BMPR2 Gene ,General Medicine ,medicine.disease ,congenital heart disease ,BMPR2 ,Treatment Outcome ,030228 respiratory system ,Cardiology ,business - Abstract
Severe pulmonary arterial hypertension (PAH) rarely develops in children with an atrial septal defect (ASD), even those with a large defect. We herein report the case of a 27-year-old man with a moderate-sized secundum ASD and right ventricular failure due to severe PAH, which developed in his early teens. He was diagnosed as having a genetic mutation of the bone morphogenetic protein receptor-2 (BMPR2) gene and was successfully treated with bilateral lung transplantation with ASD path closure. In patients with congenital heart disease, a genetic analysis may provide information about the lifetime risk of developing PAH.
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- 2017
188. AMBRA1 is involved in T cell receptor-mediated metabolic reprogramming through an ATG7-independent pathway
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Takahiro Suzuki, Hisako Akatsuka, Masafumi Tanaka, Yoshinori Okada, Odontuya Davaadorj, Kazuyoshi Hosomichi, Shuhei Kuga, Minoru Kimura, Yumi Iida, Chisa Okada, Nahoko Fukunishi, Kaori Masuhara, Takehito Sato, Ituro Inoue, and Masato Ohtsuka
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0301 basic medicine ,T cell ,Metabolic reprogramming ,Receptors, Antigen, T-Cell ,Biophysics ,Autolysosome formation ,Mice, Transgenic ,Biology ,Mitochondrion ,Autophagy-Related Protein 7 ,Biochemistry ,Mice ,03 medical and health sciences ,0302 clinical medicine ,Autophagy ,Tumor Cells, Cultured ,medicine ,Animals ,Glycolysis ,Molecular Biology ,Adaptor Proteins, Signal Transducing ,Mice, Knockout ,T-cell receptor ,Cell Biology ,Cell biology ,030104 developmental biology ,medicine.anatomical_structure ,Metabolic regulation ,030215 immunology - Abstract
Metabolic reprogramming contributes to dynamic alteration of cell functions and characteristics. In T cells, TCR-mediated signaling evokes metabolic reprogramming and autophagy. AMBRA1 is known to serve in the facilitation of autophagy and quality control of mitochondria, but the role of AMBRA1 in T cell metabolic alteration is unknown. Here, we show that AMBRA1, but not ATG7, plays a role in TCR-mediated control of glycolytic factors and mitochondrial mass, while both AMBRA1 and ATG7 are required for autolysosome formation. Our results suggested that AMBRA1 is a core factor that controls both autophagy and metabolic regulation.
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- 2017
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189. Model of lung cancer surgery risk derived from a Japanese nationwide web-based database of 78 594 patients during 2014–2015†
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Takashi Kondo, Kohei Yokoi, Masayuki Chida, Meinoshin Okumura, Shunsuke Endo, Haruhiko Kondo, Jun Nakajima, Masami Sato, Koichi Yoshida, Yoshinori Okada, Shinichi Toyooka, Koji Chihara, Hiroaki Miyata, Eriko Fukuchi, Morihito Okada, Yukio Sato, and Norihiko Ikeda
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Male ,Pulmonary and Respiratory Medicine ,medicine.medical_specialty ,Lung Neoplasms ,Cirrhosis ,Databases, Factual ,Thoracic ,Risk model ,medicine.medical_treatment ,Pulmonary Surgical Procedures ,030204 cardiovascular system & hematology ,Risk Assessment ,03 medical and health sciences ,Pneumonectomy ,Postoperative Complications ,0302 clinical medicine ,Japan ,Risk Factors ,Internal medicine ,Web based database ,medicine ,Humans ,Hospital Mortality ,Registries ,Lung cancer ,Aged ,Neoplasm Staging ,Internet ,Lung cancer surgery ,Performance status ,business.industry ,Mortality rate ,General Medicine ,Middle Aged ,medicine.disease ,Surgery ,030220 oncology & carcinogenesis ,Female ,Morbidity ,Cardiology and Cardiovascular Medicine ,business ,Nationwide survey - Abstract
OBJECTIVES Using data obtained from a Japanese nationwide annual database with web-based data entry, we developed a risk model of mortality and morbidity after lung cancer surgery. METHODS The characteristics and operative and postoperative data from 80 095 patients who underwent lung cancer surgery were entered into the annual National Clinical Database of Japan data sets for 2014 and 2015. After excluding 1501 patients, the development data set for risk models included 38 277 patients entering in 2014 and the validation data set included 40 317 patients entering in 2015. Receiver–operating characteristic curves were generated for the outcomes of mortality and composite mortality/major morbidity. The concordance index was used to assess the discriminatory ability and validity of the model. RESULTS The 30-day mortality and overall mortality rates, including in-hospital deaths, were 0.4% and 0.8%, respectively, in 2014, and 0.4% and 0.8%, respectively, in 2015. The rate of major morbidity was 5.6% in 2014 and 5.6% in 2015. Several risk factors were significantly associated with mortality, namely, male sex, performance status, comorbidities of interstitial pneumonia and liver cirrhosis, haemodialysis and the surgical procedure pneumonectomy. The concordance index for mortality and composite mortality/major morbidity was 0.854 (P
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- 2017
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190. Decrease in an anti-ageing factor, growth differentiation factor 11, in chronic obstructive pulmonary disease
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Rie Tanaka, Tadahisa Numakura, Satoru Yanagisawa, Yuichiro Hashimoto, Satoshi Suzuki, Yasushi Hoshikawa, Shinsaku Togo, Kei Sato, Hisatoshi Sugiura, Akira Koarai, Motohiko Miura, Katsuhiro Onodera, Masaru Yanai, Yoshinori Okada, Tatsuma Okazaki, Yorihiko Kyogoku, Seiichi Kobayashi, Tsutomu Tamada, Mitsuhiro Yamada, Naoya Fujino, and Masakazu Ichinose
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Male ,0301 basic medicine ,Pulmonary and Respiratory Medicine ,medicine.medical_specialty ,Blotting, Western ,medicine.disease_cause ,Pulmonary function testing ,Mice ,Plasma ,Pulmonary Disease, Chronic Obstructive ,03 medical and health sciences ,0302 clinical medicine ,Downregulation and upregulation ,In vivo ,Smoke ,Internal medicine ,medicine ,Animals ,Humans ,RNA, Messenger ,Cellular Senescence ,Aged ,COPD ,Reverse Transcriptase Polymerase Chain Reaction ,business.industry ,medicine.disease ,Immunohistochemistry ,Respiratory Function Tests ,Growth Differentiation Factors ,Disease Models, Animal ,030104 developmental biology ,Endocrinology ,030228 respiratory system ,Bone Morphogenetic Proteins ,GDF11 ,Female ,business ,Oxidative stress ,Transforming growth factor - Abstract
Rationale Cellular senescence is observed in the lungs of patients with COPD and may contribute to the disease pathogenesis. Growth differentiation factor 11 (GDF11) belongs to the transforming growth factor β superfamily and was recently reported to be a circulating protein that may have rejuvenating effects in mice. We aimed to investigate the amounts of GDF11 in the plasma and the lungs of patients with COPD and elucidate the possible roles of GDF11 in cellular senescence. Methods The plasma levels of GDF11 were investigated in two separate cohorts by western blotting. The localisation and expression of GDF11 in the lungs were investigated by immunohistochemistry and quantitative reverse transcription PCR, respectively. The effects of GDF11 on both cigarette smoke extract (CSE)-induced cellular senescence in vitro and on elastase-induced cellular senescence in vivo were investigated. Results The levels of plasma GDF11 in the COPD group were decreased compared with the control groups in the two independent cohorts. The levels of plasma GDF11 were significantly positively correlated with pulmonary function data. The mRNA expression of GDF11 in mesenchymal cells from the COPD group was decreased. Chronic exposure to CSE decreased the production of GDF11. Treatment with GDF11 significantly inhibited CSE-induced cellular senescence and upregulation of inflammatory mediators, partly through Smad2/3 signalling in vitro. Daily GDF11 treatment attenuated cellular senescence and airspace enlargement in an elastase-induced mouse model of emphysema. Conclusions The decrease in GDF11 may be involved in the cellular senescence observed in COPD.
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- 2017
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191. Printed Multi-color Devices using Oxidative Electrochromic Materials
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Toshiya Sagisaka, Yutani Keiichiro, Yoshinori Okada, Takauji Keigo, Masato Shinoda, Daisuke Goto, Satoshi Yamamoto, Tohru Yashiro, and Kaneko Fuminari
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Materials science ,Polymers and Plastics ,010405 organic chemistry ,Electrochromism ,Organic Chemistry ,Materials Chemistry ,Nanotechnology ,010402 general chemistry ,Electrochromic devices ,01 natural sciences ,Inkjet printing ,0104 chemical sciences - Published
- 2017
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192. The Clinical Course of Surgically Treated Pleomorphic Carcinoma of the Lung
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Yasushi Matsuda, Akira Sakurada, Ken Onodera, Yasushi Hoshikawa, Hideki Mitomo, Masafumi Noda, Chiaki Endo, Yoshinori Okada, and Fumihiko Hoshil
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Pulmonary and Respiratory Medicine ,Pathology ,medicine.medical_specialty ,Lung ,Adjuvant chemotherapy ,business.industry ,Clinical course ,Pleomorphic carcinoma ,03 medical and health sciences ,0302 clinical medicine ,medicine.anatomical_structure ,030228 respiratory system ,Oncology ,030220 oncology & carcinogenesis ,medicine ,business - Published
- 2017
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193. Extrapulmonary Problems Limit the Outcome of Lung Transplantation in Idiopathic Pleuroparenchymal Fibroelastosis: A Multi-Center Study in Japan
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Shinji Otani, Toshio Shiotani, Yoshinori Okada, Hiroshi Date, Haruhiko Shiiya, Masaaki Sato, Masayuki Chida, Ichiro Yoshino, Jun Nakajima, Takahiro Oto, Tomohiro Handa, Toshihiko Moroga, Masato Minami, Go Hatachi, Soichiro Funaki, Takeshi Shiraishi, Kiminobu Tanizawa, Yasushi Matsuda, and Toyofumi F. Chen-Yoshikawa
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Pulmonary and Respiratory Medicine ,Transplantation ,medicine.medical_specialty ,Lung ,business.industry ,medicine.medical_treatment ,respiratory system ,medicine.disease ,respiratory tract diseases ,Pulmonary function testing ,Idiopathic pulmonary fibrosis ,medicine.anatomical_structure ,Fibrosis ,Internal medicine ,Multi center study ,medicine ,Lung transplantation ,Surgery ,In patient ,Cardiology and Cardiovascular Medicine ,business - Abstract
Purpose Idiopathic pleurparenchymal fibroelastosis (IPPFE) is a relatively new disease entity of interstitial pneumonia characterized by upper lobe dominant fibrosis and flat chest. The purpose of this study is to evaluate the outcome of lung transplantation for IPPFE in comparison with idiopathic pulmonary fibrosis (IPF). Methods We retrospectively reviewed patients with IPPFE and those with IPF aged 20 or over who underwent lung transplantation between 1998 and 2018. Data were collected from all nine lung transplant centers in Japan, under the support of Japanese Society of Lung and Heart-Lung Transplantation. Results One hundred patients were eligible, including 31 IPPFE and 69 IPF patients. Patients with IPPFE were more likely to be women (58% vs 28%; P Conclusion The survival of patients with IPPFE after lung transplantation was comparable with those with IPF. However, patients with IPPFE showed longer ICU stay, limited improvement in pulmonary function, and no improvement in low BMI, suggesting systemic or extrapulmonary problems such as stiff chest wall in patients with IPPFE.
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- 2020
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194. Effect of CTLA4-Ig on Obliterative Bronchiolitis in a Mouse Intrapulmonary Tracheal Transplantation Model.
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Yamato Suzuki, Hisashi Oishi, Masahiko Kanehira, Yasushi Matsuda, Takashi Hirama, Masafumi Noda, and Yoshinori Okada
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- 2021
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195. Advanced glycation end products and receptor of advanced glycation end products
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Mizue, OKADA and Yoshinori, OKADA
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- 2016
196. Sustained-Release Tacrolimus Stabilizes Decline of Forced Expiratory Volume in 1 Second Through Decreasing Fluctuation of Its Trough Blood Level
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Yoshinori Okada, Akira Sakurada, Fumihiko Hoshi, Miki Akiba, Yasushi Matsuda, Masafumi Noda, Tetsu Sado, Hiromichi Niikawa, Hisashi Oishi, Tatsuaki Watanabe, and S. Eba
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Adult ,Male ,Blood level ,medicine.medical_specialty ,Adolescent ,medicine.medical_treatment ,Calcineurin Inhibitors ,Urology ,Bronchiolitis obliterans ,030230 surgery ,Drug Administration Schedule ,Tacrolimus ,Young Adult ,03 medical and health sciences ,Postoperative Complications ,0302 clinical medicine ,Forced Expiratory Volume ,medicine ,Humans ,Bronchiolitis Obliterans ,Transplantation ,Lung ,business.industry ,Middle Aged ,medicine.disease ,Respiratory Function Tests ,Calcineurin ,medicine.anatomical_structure ,Immunosuppressive drug ,Delayed-Action Preparations ,Cyclosporine ,Trough level ,Female ,030211 gastroenterology & hepatology ,Surgery ,Bone marrow ,business ,human activities ,Immunosuppressive Agents ,Lung Transplantation - Abstract
Calcineurin inhibitors are a commonly used immunosuppressive drug and over 80% of lung transplant (LTx) recipients use tacrolimus. Sustained-release tacrolimus (SRT) was developed as a once-daily formulation, resulting in slower release and reduction in peak concentration compared with twice-daily immediate-release tacrolimus (IRT). Previous reports indicate that SRT may carry fewer side effects than IRT; however, the impact of SRT in bronchiolitis obliterans syndrome (BOS) after LTx is unclear.Our study objective was to evaluate the effect of SRT in BOS after LTx.We investigated the effect of SRT for BOS among 75 LTx recipients who were alive in 2017 in our LTx program. All analyses were carried out using student t test or F test.Thirty-five recipients took IRT, 32 recipients used SRT, 7 recipients used cyclosporine, and 1 patient who received bone marrow and a lung graft from the same donor did not use a calcineurin inhibitor. The most frequent reason for conversion of IRT to SRT was kidney dysfunction, followed by other IRT complications. Five recipients underwent conversion of IRT to SRT because of decline of forced expiratory volume in 1 second (FEV1) with fluctuation of the tacrolimus trough level. After induction of SRT, the fluctuation of the tacrolimus trough level was significantly reduced in 4 of 5 patients (P .05). Before drug form conversion, the FEV1 in these 5 patients was significantly decreased; however, this exacerbation of FEV1 was attenuated after SRT induction (P .05).SRT appeared to stabilize decline of FEV1 in patients with BOS possibly due to reducing the fluctuation of tacrolimus trough blood concentration.
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- 2018
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197. [Successful Multidisciplinary Treatment Accomplished by Collaboration of Multiple Clinical Departments for Synchronous Quadruple Cancer]
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Shunsuke, Eba, Hirotsugu, Notsuda, Fumihiko, Hoshi, Hisashi, Oishi, Yasushi, Matsuda, Tetsu, Sado, Masafumi, Noda, Akira, Sakurada, Ken, Saijo, Akira, Okoshi, Naoki, Tanaka, and Yoshinori, Okada
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Male ,Neoplasms, Multiple Primary ,Esophageal Neoplasms ,Antineoplastic Combined Chemotherapy Protocols ,Humans ,Fluorouracil ,Cisplatin ,Middle Aged ,Neoplasm Recurrence, Local - Abstract
A 60-year-old man consulted a clinic complains of sore throat. Squamous cell carcinoma of the hypopharynx and adenocarcinoma of the stomach were pointed out and he was refered to our hospital. As a result of detailed systemic examination, squamous cell carcinoma of the esophagus and squamous cell carcinoma of the right lung were also pointed out, which led to a diagnosis of synchronous quadruple cancer. On the basis of discussions among multiple clinical departments, systemic chemotherapy with cisplatin(CDDP), fluorouracil (5-FU) and docetaxel(DTX) was preceded locolegional therapies. After that, complete thoracoscopic right lower lobectomy and then a laparoscopic distal gastrectomy was performed. Radiation therapy was applied for hypopharyngeal cancer. Finally, endoscopic submucosal dissection for esophageal cancer was performed. Twenty months have passed since the last treatment, the patient is alive with a relapse-free condition.
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- 2019
198. PD-L1 Induction by Cancer-Associated Fibroblast-Derived Factors in Lung Adenocarcinoma Cells
- Author
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Shuko Hata, Ryoko Saito, Ikuro Sato, Yoshinori Okada, Chihiro Inoue, Yasuhiro Miki, Hironobu Sasano, and Jiro Abe
- Subjects
0301 basic medicine ,Cancer Research ,cancer associated fibroblasts ,lcsh:RC254-282 ,Article ,03 medical and health sciences ,0302 clinical medicine ,Epidermal growth factor ,PD-L1 ,medicine ,tumor microenvironment ,Lung cancer ,smooth muscle actin ,Tumor microenvironment ,biology ,FOXP3 ,medicine.disease ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,lung adenocarcinoma ,030104 developmental biology ,Oncology ,programmed death ligand 1 ,030220 oncology & carcinogenesis ,Recurrent Lung Adenocarcinoma ,biology.protein ,Cancer research ,α-smooth muscle actin ,Adenocarcinoma ,Immunohistochemistry - Abstract
Cancer-associated fibroblasts (CAFs) exert various effects upon biological behaviours of cancer. In this study, we examined the correlation of CAFs with the intra-tumoural immune system in the lung adenocarcinoma microenvironment. We studied 27 and 113 cases of lung adenocarcinoma tentatively as Cohorts 1 and 2, respectively. The patients in Cohort 1 received epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) for recurrent lung adenocarcinoma. α-smooth muscle actin (α-SMA), a surrogate marker for CAFs, was examined by immunohistochemistry. We then examined the effects of CAFs isolated from lung cancer tissues on programmed death ligand 1 (PD-L1) expression in lung adenocarcinoma cell lines. No significant associations were detected between α-SMA status and the ratios of CD8/CD4 and Foxp3/CD8 in Cohort 1. However, α-SMA status was significantly associated with PD-L1 status in both Cohorts 1 and 2. Conditioned medium of CAFs significantly induced PD-L1 expression in lung adenocarcinoma cell lines, A549, PC-9, and H1975. Among the cytokines examined by antibody array, C-X-C motif chemokine ligand 2 (CXCL2) increased PD-L1 mRNA expression in these cell lines. CXCL2 is therefore considered to have a potential to induce PD-L1 expression in lung adenocarcinoma cells as a result of an interaction between carcinoma cells and CAFs. These findings did firstly demonstrate that CAFs indirectly influenced tumour immunity through increasing PD-L1 expression in lung adenocarcinoma cells.
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- 2019
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199. Comprehensive Metabolome Analysis Reveals New Mechanism of Anti-Fibrotic Factor Stanniocalcin-1 (STC1) Which Modulate Epigenetic Regulation and Oxidative Stress
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D. Saigusa, Tokiwa Tamai, Masao Tabata, Hiromasa Ogawa, Yoshinori Okada, Shinya Ohkouchi, Hajime Kurosawa, Masahiko Kanehira, and Toshiya Irokawa
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Anti fibrotic ,Stanniocalcin ,Mechanism (biology) ,Chemistry ,Metabolome ,medicine ,STC1 ,Epigenetics ,medicine.disease_cause ,Oxidative stress ,Cell biology - Published
- 2019
- Full Text
- View/download PDF
200. Quercetin, caffeic acid and resveratrol regulate circadian clock genes and aging-related genes in young and old human lung fibroblast cells
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Mizue Okada and Yoshinori Okada
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0301 basic medicine ,Aging ,NF-E2-Related Factor 2 ,Circadian clock ,CLOCK Proteins ,Resveratrol ,Biology ,Cell Line ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Glucocorticoid receptor ,Caffeic Acids ,Receptors, Glucocorticoid ,Sirtuin 1 ,Circadian Clocks ,Genetics ,medicine ,Caffeic acid ,Humans ,Fibroblast ,Molecular Biology ,Age Factors ,food and beverages ,ARNTL Transcription Factors ,Polyphenols ,General Medicine ,Fibroblasts ,Cell biology ,Circadian Rhythm ,CLOCK ,030104 developmental biology ,medicine.anatomical_structure ,chemistry ,030220 oncology & carcinogenesis ,Quercetin ,hormones, hormone substitutes, and hormone antagonists ,PER1 - Abstract
The circadian timing system of mammals is synchronized in concert with a central clock, but is also influenced by additional stimuli, including nutrients. However, little research has been done on polyphenols other than resveratrol and there seem to be no studies on their influence on young and old cells. The purpose of this study was to analyse the potential effects of quercetin, caffeic acid, and resveratrol on young and old fibroblast cells in the expressions of different clock genes and aging-related genes, and further investigate the mechanism. The mRNA expression of different clock genes and aging-related genes was assessed by quantitative real-time PCR. The protein levels of clock genes (BMAL1, PER1 and SIRT1) and glucocorticoid receptor α (GRα) were assessed by ELISA. Quercetin and caffeic acid in old fibroblast cells showed higher clock gene expression than resveratrol, quercetin increased Sirt1 expression, and caffeic acid increased Sirt6 expression indicating the possibility of an anti-aging effect. Also, quercetin and caffeic acid showed higher clock-controlled gene (Sirt1 and NR1D1) expression than resveratrol in young fibroblast cells. It appears that caffeic acid acts on NRF2 expression, and in turn to the actions of GRα, GDF11, Sirt1, and Sirt6. Regarding the increased expression of Per1, the activation effect on NR1D1 was confirmed only for caffeic acid in young fibroblast cells. Our results have confirmed the interplay of the circadian clock genes and cellular aging.
- Published
- 2019
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