329 results on '"Katsuya Hirano"'
Search Results
2. Editor's Introduction
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Katsuya Hirano
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Cultural Studies ,History ,Literature and Literary Theory ,Visual Arts and Performing Arts - Published
- 2022
3. Nab-Paclitaxel for Previously Treated Advanced Non–Small Cell Lung Cancer: Analysis of Safety and Efficacy for Patients With Renal Impairment
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Yasuto, Yoneshima, Satoshi, Morita, Masahiko, Ando, Atsushi, Nakamura, Shunichiro, Iwasawa, Hiroshige, Yoshioka, Yasuhiro, Goto, Masafumi, Takeshita, Toshiyuki, Harada, Katsuya, Hirano, Tetsuya, Oguri, Masashi, Kondo, Satoru, Miura, Yukio, Hosomi, Terufumi, Kato, Toshio, Kubo, Junji, Kishimoto, Nobuyuki, Yamamoto, Yoichi, Nakanishi, and Isamu, Okamoto
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Pulmonary and Respiratory Medicine ,Cancer Research ,Lung Neoplasms ,Oncology ,Carcinoma, Non-Small-Cell Lung ,Creatinine ,Antineoplastic Combined Chemotherapy Protocols ,Humans ,Docetaxel - Abstract
Renal impairment can affect treatment tolerability and outcome in individuals with cancer. We aimed to assess the safety and efficacy of nab-paclitaxel for previously treated patients with advanced non-small cell lung cancer (NSCLC) and renal impairment enrolled in a phase 3 trial of nab-paclitaxel vs. docetaxel.Previously treated NSCLC patients were randomly allocated (1:1) to receive docetaxel (60 mg/m²) on day 1 or nab-paclitaxel (100 mg/m²) on days 1, 8, and 15 of a 21-day cycle. Safety and efficacy outcomes of treatment were evaluated according to renal function.Among the 503 patients enrolled in the phase 3 trial, 17.3% had moderate renal impairment (creatinine clearance of ≤50 mL/min, n = 49 for docetaxel and n = 38 for nab-paclitaxel) and 53.1% had mild renal impairment (creatinine clearance of50 to ≤80 mL/min, n = 133 for docetaxel and n = 134 for nab-paclitaxel). For patients with renal impairment, the incidence of febrile neutropenia was lower in the nab-paclitaxel group than in the docetaxel group. The difference in treatment efficacy for nab-paclitaxel vs. docetaxel among patients with moderate or mild renal impairment was similar to that among the overall study population.Nab-paclitaxel was found to be tolerable and beneficial for previously treated patients with advanced NSCLC and mild or moderate renal impairment.
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- 2022
4. Eiichiro Azuma. In Search of Our Frontier: Japanese American and Settler Colonialism in the Construction of Japan’s Borderless Empire
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Katsuya Hirano
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Archeology ,History ,Museology - Published
- 2022
5. Influence of social isolation and loneliness on the prognosis of advanced lung cancer patients: a prospective cohort study
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Tomoyasu Takemura, Yuki Kataoka, Nanami Ashi, Chigusa Shirakawa, Koya Okazaki, Azusa Sakurai, Takuma Imakita, Shunkichi Ikegaki, Hirotaka Matsumoto, Emiko Saito, Hirohito Takata, Sawako Kaku, Nobuko Wada, Mariko Shinomiya, Takehiro Otoshi, Masatoshi Shimada, Junichi Nikaido, Reika Iki, Katsuya Hirano, Tomoyuki Hirai, Kazuo Endo, Masataka Hirabayashi, and Toru Naganuma
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Lung Neoplasms ,Social Isolation ,Oncology ,Loneliness ,Humans ,Prospective Studies ,Prognosis - Abstract
Purpose The purpose of this study was to investigate the impact of social isolation and loneliness on the overall survival and death at home in patients with lung cancer. Methods This prospective cohort study was conducted in a Japanese tertiary hospital. The enrollment period was from April 2018 to March 2020. Patients with pathologically diagnosed advanced lung cancer were included in this study. The primary outcome was overall survival, whereas the secondary outcome was death at home. The exposures were social isolation and loneliness. Results A total of 211 patients were enrolled and divided into two groups and further into quartiles according to their social isolation and loneliness level, respectively. The hazard ratios of social isolation were 1.65 (95% confidence interval; 1.12 to 2.44) and 1.87 (95% confidence interval; 1.15 to 3.03) in the univariate analysis, while 1.40 (95% confidence interval; 0.92 to 2.13) in the multivariate analysis with complete case and multiple imputation. The odds ratio of death at home with social isolation was 3.47 (95% confidence interval; 1.08 to 11.1) in the multivariate analysis with multiple imputation. Loneliness was not associated with overall survival or death at home. Conclusions Our study suggests that social isolation may be related to overall survival and death at home among patients with advanced lung cancer. More attention should be given to such patients at the time of diagnosis.
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- 2022
6. Potential of the TRPM7 channel as a novel therapeutic target for pulmonary arterial hypertension
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Keizo, Hiraishi, Lin Hai, Kurahara, Kaori, Ishikawa, Tetsuhiko, Go, Naoya, Yokota, Yaopeng, Hu, Takayuki, Fujita, Ryuji, Inoue, and Katsuya, Hirano
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Pulmonary Arterial Hypertension ,Transient Receptor Potential Channels ,Physiology ,Hypertension, Pulmonary ,Myocytes, Smooth Muscle ,Humans ,TRPM Cation Channels ,Familial Primary Pulmonary Hypertension ,General Medicine ,Protein Serine-Threonine Kinases ,Pulmonary Artery ,Vascular Remodeling ,Cell Proliferation - Abstract
Pulmonary arterial hypertension (PAH) is an intractable vascular disease characterized by a progressive increase in pulmonary vascular resistance caused by pulmonary vascular remodeling, which ultimately leads to right-sided heart failure. PAH remains incurable, despite the development of PAH-targeted therapeutics centered on pulmonary artery relaxants. It is necessary to identify the target molecules that contribute to pulmonary artery remodeling. Transient receptor potential (TRP) channels have been suggested to modulate pulmonary artery remodeling. Our study focused on the transient receptor potential ion channel subfamily M, member 7, or the TRPM7 channel, which modulates endothelial-to-mesenchymal transition and smooth muscle proliferation in the pulmonary artery. In this review, we summarize the role and expression profile of TRPM7 channels in PAH progression and discuss TRPM7 channels as possible therapeutic targets. In addition, we discuss the therapeutic effect of a Chinese herbal medicine, Ophiocordyceps sinensis (OCS), on PAH progression, which partly involves TRPM7 inhibition.
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- 2022
7. Critical role of Rho proteins in myosin light chain di-phosphorylation during early phase of endothelial barrier disruption
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Mayumi Hirano and Katsuya Hirano
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Myosin Light Chains ,Swine ,Physiology ,Thrombin ,Animals ,Endothelial Cells ,Actins - Abstract
We previously reported the Rho-associated coiled-coil containing protein kinase (ROCK)-mediated di-phosphorylation of myosin light chain (MLC) and actin bundle formation at the cell periphery as early events of the endothelial barrier disruption. We herein examined the role of RhoA during early events of barrier disruption. Treatment of cultured porcine aortic endothelial cells with simvastatin prevented the decrease in trans-endothelial electrical resistance, MLC di-phosphorylation and peripheral actin bundle formation seen 3 min after thrombin stimulation. Co-treatment with geranylgeranyl pyrophosphate rescued the thrombin-induced events. Thrombin increased a GTP-bound form of RhoA and phosphorylation of myosin phosphatase target subunit 1 (MYPT1) at the ROCK site. The intracellular introduction of the inhibitory protein of RhoA inhibited the thrombin-induced di-phosphorylation of MLC. However, knockdown of either one of RhoA, RhoB or RhoC failed to inhibit thrombin-induced MLC di-phosphorylation. The findings suggest that Rho proteins play a critical role during early events of thrombin-induced barrier disruption.
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- 2022
8. Settler Colonialism as Encounter
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Katsuya Hirano
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- 2022
9. Precut technique using an injection needle: A retrospective study on a new ancillary procedure for pleural biopsy
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Yasuyuki Mizumori, Katsuya Hirano, Nobuya Hirata, Ryota Hiraoka, Sayaka Takahashi, Ryota Kominami, Kohei Miyake, Masaki Takenouchi, Tomohiro Kato, Sachie Kume, Sachiko Higashino, Yasuharu Nakahara, and Tetsuji Kawamura
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Male ,Pleural Effusion ,Biopsy ,Thoracoscopy ,Humans ,Pleura ,Female ,General Medicine ,Pleural Diseases ,Aged ,Retrospective Studies - Abstract
The effectiveness of thoracoscopic biopsy as a diagnostic method for pleural diseases has been reported; however, obtaining a sufficient specimen size is sometimes difficult. Therefore, an ancillary technique, the precut technique using an injection needle, was devised to address this problem. This study aimed to evaluate the effectiveness and safety of the novel precut technique in patients with undiagnosed pleural effusion. This retrospective study included 22 patients who underwent pleural biopsy using the precut technique to examine exudative pleural effusion of unknown etiology. Thoracoscopy was performed under local anesthesia. The biopsy procedure was performed as follows: a needle was inserted into the pleura around the lesion using a semiflexible thoracoscope; the needle was positioned to make an incision in the pleura while injecting 1% lidocaine with epinephrine and lifting the pleura from the fascia; 2 or 3 precut incision lines were arranged in a triangle; and the specimen was obtained from the parietal pleura using forceps or a cryoprobe. Patient data including age, number of biopsies, biopsy specimen size, pathological and final diagnosis, and postoperative complications were examined. All patients were male with an average age of 74 years. Pleural effusion was found on the right and left sides in 16 and 6 patients, respectively. The average major axis of the biopsy specimens was 18 mm (range, 10-30 mm), which was sufficient to establish a pathological diagnosis. Only 1 patient experienced minor temporal bleeding as a complication. The precut technique enabled the procurement of specimens sufficient in size for pleural biopsy.
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- 2022
10. Efficacy of Olanzapine in Addition to Standard Triplet Antiemetic Therapy for Cisplatin-Based Chemotherapy
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Masakazu Abe, Takuhiro Yamaguchi, Yukiyoshi Fujita, Tomoyasu Nishimura, Koichi Kitagawa, Naoki Inui, Katsuya Hirano, Yukio Sakata, Hirotoshi Iihara, Yuichi Shibuya, Kenichi Suzuki, Kazuhiko Shibata, Kensuke Hori, Haruko Daga, Toshiaki Nakayama, Yasuhiko Sakata, Takako Yanai Takahashi, Sadamoto Zenda, and Hironobu Hashimoto
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General Medicine - Abstract
ImportanceIt is unknown whether olanzapine combined with triplet antemetic therapy is effective for all patients undergoing highly emetogenic chemotherapy. A secondary analysis of randomized clinical trials using olanzapine may provide insight into the effectiveness of olanzapine for chemotherapy-induced nausea and vomiting (CINV), including cisplatin.ObjectiveTo examine the add-on effect of olanzapine according to risk factors for CINV.Design, Setting, and ParticipantsThis preplanned secondary analysis evaluated results of the J-FORCE trial, a large double-blind, placebo-controlled phase 3 randomized clinical trial conducted in Japan from February 9, 2017, to July 18, 2018. Participants were enrolled from 26 participating hospitals across Japan and included patients aged 20 to 75 years who had a malignant tumor and were cisplatin-naive. The efficacy analysis population of the J-FORCE trial was analyzed according to allocation adjustment factors (sex [male or female], age [≥55 years or 2 or 2]) and patient-related risk factors (history of motion sickness, drinking habit [defined as alcoholic drinks consumption in excess of occasional drinking], and history of morning sickness during pregnancy). Statistical analysis was performed from February 18 to April 18, 2020.InterventionsPatients were randomized 1:1 to receive 5 mg of olanzapine or placebo combined with standard triplet antiemetic therapy.Main Outcomes and MeasuresThe primary end point was complete response (CR, defined as no vomiting and no use of rescue medication) in the delayed phase (24-120 hours after cisplatin-based chemotherapy administration). Secondary end points were CR, complete control, and total control in the acute, delayed, and overall phases for 6 CINV risk factors as well as time to treatment failure. The CR point estimates and 95% CIs of the differences between groups were calculated, and a Mantel-Haenszel test was performed.ResultsOf the 705 patients (mean [SD] age, 63.0 [9.2] years; 471 males [66.8%]) included in the efficacy analysis population; 581 patients (82.4%) were 55 years or older, and 526 (74.6%) were treated with a cisplatin dose of 70 mg/m2 or more. Risk difference (RD) for a CR in the delayed phase was significantly greater in the olanzapine group than the placebo group in males (RD, 12.6% [95% CI, 5.0%-20.1%]; P = .001); in females (RD, 14.5% [95% CI, 2.2%-26.3%]; P = .02); in those 55 years or older (RD, 11.1% [95% CI, 3.9%-18.2%]; P = .003) or younger than 55 years (RD, 23.6% [95% CI, 7.3%-38.3%]; P = .005); for a cisplatin dose of 70 mg/m2 or more (RD, 13.5% [95% CI, 5.9%-21.0%]; P P P = .001) or without a drinking habit (RD, 12.0% [95% CI, 2.5%-21.3%]; P = .01); and for those with a history of morning sickness during pregnancy (RD, 27.2% [9.7%-42.6%]; P = .002). In other subgroups, a delayed CR was higher in the olanzapine group than the placebo group, although not significantly higher.Conclusions and RelevanceResults of this study suggest a benefit of using 5 mg of olanzapine plus triplet antiemetic therapy to counter CINV regardless of the presence or absence of risk factors.Trial RegistrationUniversity Hospital Medical Information Network Clinical Trials Registry Identifier: UMIN000024676
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- 2023
11. Influence of loneliness and social isolation on the diagnosis and treatment of Japanese patients with advanced lung cancer: a prospective cohort study
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Yuki Kataoka, Azusa Sakurai, Shunkichi Ikegaki, Emiko Saito, Nobuko Wada, Masatoshi Shimada, Reika Iki, Takehiro Otoshi, Sawako Kaku, Takuma Imakita, Mariko Shinomiya, Koya Okazaki, Hirohito Takata, Katsuya Hirano, Hirotaka Matsumoto, Toru Naganuma, Tomoyasu Takemura, Masataka Hirabayashi, Kazuo Endo, Junichi Nikaido, Chigusa Shirakawa, and Tomoyuki Hirai
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medicine.medical_specialty ,Lung Neoplasms ,Gene mutation ,Tertiary referral hospital ,03 medical and health sciences ,0302 clinical medicine ,Japan ,Internal medicine ,medicine ,Humans ,Prospective Studies ,030212 general & internal medicine ,Social determinants of health ,Social isolation ,Lung cancer ,Prospective cohort study ,Advanced and Specialized Nursing ,Performance status ,business.industry ,Loneliness ,medicine.disease ,Anesthesiology and Pain Medicine ,Social Isolation ,030220 oncology & carcinogenesis ,medicine.symptom ,business - Abstract
Background Social determinants of health (SDHs) are social factors that affect human health; loneliness and social isolation are core SDH factors. There is a possibility that SDHs are related to passive decisionmaking. However, few studies have evaluated SDHs, especially social isolation and loneliness, among lung cancer patients. This study aims to investigate the effects of social isolation and loneliness on the diagnosis and treatment of Japanese lung cancer patients. Methods This is a prospective cohort study that was conducted in a tertiary referral hospital in Japan (University Hospital Medical Information Network registration: UMIN000031810). The enrollment period was between April 2018 and March 2020. Patients with clinical and/or pathological diagnosis of lung cancer were enrolled in this study. Exposures were social isolation and loneliness, and main outcomes were diagnosis methods and whether the initial treatment involved active therapy or best supportive care (BSC). The confounding factors were defined as sex, age, smoking status, respiratory symptoms, weight loss, presentation with any symptoms, Eastern Cooperative Oncology Group (ECOG) performance status, tumor nodes metastasis (TNM) classification, driver gene mutations [i.e., epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK)], and programmed death-ligand 1 (PD-L1) tumor proportion score. Results The study enrolled 264 patients who were divided into quartiles according to their loneliness scores and into two groups according to the social isolation level. Univariate analysis, complete case analysis, and multivariate analysis with multiple imputation failed to detect significant differences in diagnostic method or initial treatment strategy according to loneliness or social isolation level. Conclusions Physicians may not need to consider a patient's loneliness and/or social isolation when diagnosing lung cancer and selecting treatment under universal health insurance coverage. Further studies are needed to understand the influences of loneliness and social isolation on the prognosis of lung cancer patients.
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- 2021
12. Prospects of the landscape fields from Great East Japan Earthquake Memorial Parks
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Ryuichi Wakisaka, Takahiro Sasaki, Katsuya Hirano, Isaku Okuyama, Kenji Fukuhara, and Noriko Akita
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- 2021
13. Sequential therapy of crizotinib followed by alectinib for non-small cell lung cancer harbouring anaplastic lymphoma kinase rearrangement (WJOG9516L): A multicenter retrospective cohort study
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Toshihide Yokoyama, D. Fujimoto, Takuya Aoki, Takashi Yokoi, Kensuke Suzuki, Kazuhiko Nakagawa, Akihiro Bessho, Ken Maeno, Kazumi Nishino, Takashi Seto, Koji Azuma, Satoshi Watanabe, Nobuyuki Yamamoto, Hiroaki Akamatsu, Osamu Hataji, Shinya Sakata, Hidetoshi Hayashi, Motoyasu Okuno, Takeharu Yamanaka, Toshiyuki Kozuki, Yoshihiro Hattori, Tomoya Fukui, Kentaro Tanaka, Atsushi Nakamura, Akihito Kubo, Katsuya Hirano, Koichi Azuma, Haruko Daga, Atsuhisa Tamura, Masahide Mori, Satoru Miura, Shigeto Hontsu, Yuko Oya, Kentaro Ito, and Haruki Kobayashi
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Adult ,Male ,0301 basic medicine ,Alectinib ,Oncology ,endocrine system ,Cancer Research ,medicine.medical_specialty ,Lung Neoplasms ,Time Factors ,Population ,Carbazoles ,03 medical and health sciences ,0302 clinical medicine ,Crizotinib ,Japan ,Piperidines ,Carcinoma, Non-Small-Cell Lung ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,Biomarkers, Tumor ,Humans ,Medicine ,Anaplastic lymphoma kinase ,Anaplastic Lymphoma Kinase ,education ,Lung cancer ,Protein Kinase Inhibitors ,Aged ,Retrospective Studies ,Aged, 80 and over ,Gene Rearrangement ,education.field_of_study ,business.industry ,Hazard ratio ,Retrospective cohort study ,Middle Aged ,respiratory system ,medicine.disease ,Progression-Free Survival ,030104 developmental biology ,030220 oncology & carcinogenesis ,Female ,Non small cell ,business ,medicine.drug - Abstract
Background The data of sequential therapy of anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors (TKIs) in clinical practice have been limited. Methods We reviewed the clinical data of patients with ALK-rearranged non-small cell lung cancer who received crizotinib (CRZ) or alectinib (ALEC) between May 2012 and December 2016. Patients were divided into two groups based on the first-administered ALK-TKI, the CRZ or ALEC group. The combined time-to-treatment failure (TTF) was defined as the sum of the ‘TTF of CRZ’ plus the ‘TTF of ALEC’ if patients were treated with CRZ followed by ALEC in the CRZ group. The primary end-point is the comparison between the combined TTF and the TTF of ALEC in the ALEC group. Results Of 864 patients enrolled from 61 institutions, 840 patients were analysed. There were 535 of 305 patients in the CRZ/ALEC groups. The combined TTF in the CRZ group was significantly longer than TTF in the ALEC group (median, 34.4 versus 27.2 months; hazard ratio [HR], 0.709; P = 0.0044). However, there was no significant difference in overall survival (OS) between the patients who received ALEC after CRZ in the CRZ group and the patients in the ALEC group (median, 88.4 months versus. not reached; HR, 1.048; P = 0.7770). In the whole population, the CRZ group had a significantly shorter OS than the ALEC group (median, 53.6 months versus not reached; HR, 1.821, P Conclusion The combined TTF in the CRZ group was significantly longer than the TTF in the ALEC group; however, OS benefit of sequential therapy against ALEC as the first ALK-TKI was not shown.
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- 2021
14. Comparison of the harvest volume between maneuvers of endobronchial ultrasound-guided transbronchial needle aspiration including the 'cross-fanning technique'
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Yasuyuki Mizumori, Yoshihiro Seri, Katsuya Hirano, Nobuya Hirata, Masaki Takenouchi, Shin Sasaki, Yasuharu Nakahara, and Tetsuji Kawamura
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General Medicine - Published
- 2023
15. Durvalumab for patients with unresectable stage III non-small cell lung cancer and grade 1 radiation pneumonitis following concurrent chemoradiotherapy: a multicenter prospective cohort study
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Akihiro Tamiya, Masaki Kanazu, Akito Hata, Takeya Sugimoto, Junji Uchida, Yuki Sato, Motohiro Tamiya, Shunichiro Iwasawa, Masaki Kokubo, Yasushi Fukuda, Katsuya Hirano, Satoshi Hara, Takashi Yokoi, Nobuyuki Yamamoto, and D. Fujimoto
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Male ,0301 basic medicine ,medicine.medical_specialty ,Lung Neoplasms ,Durvalumab ,B7-H1 Antigen ,03 medical and health sciences ,0302 clinical medicine ,Carcinoma, Non-Small-Cell Lung ,Internal medicine ,medicine ,Humans ,Pharmacology (medical) ,Stage (cooking) ,Adverse effect ,Prospective cohort study ,Immune Checkpoint Inhibitors ,Radiation Pneumonitis ,Aged ,Neoplasm Staging ,Pneumonitis ,Aged, 80 and over ,Pharmacology ,business.industry ,Antibodies, Monoclonal ,Chemoradiotherapy ,Middle Aged ,medicine.disease ,Concurrent chemoradiotherapy ,030104 developmental biology ,Oncology ,030220 oncology & carcinogenesis ,Female ,business - Abstract
Introduction/Background Durvalumab demonstrated a good efficacy and safety in patients with unresectable stage III non-small cell lung cancer (NSCLC) after concurrent chemoradiotherapy (CCRT) in the PACIFIC trial. Although a history of radiation pneumonitis (RP) has been reported to increase the risk of pneumonitis associated with programmed death-1 inhibitors, the safety and efficacy of durvalumab in patients with baseline Grade 1 RP have not been assessed. Therefore, we carried out a multicenter prospective cohort study to evaluate the efficacy and safety of durvalumab in these patients. Patients and Methods This was a multicenter prospective cohort study of 35 patients with Grade 1 RP after CCRT and before durvalumab initiation. This study was a first prespecified analysis for the first 20 patients with the primary objective of assessing the short-term safety; it was assessed 3 months after durvalumab initiation. Results Twenty patients were enrolled in this study between March 1, 2019, and September 3, 2019. Three patients (15%) experienced drug-related Grade ≥3 adverse events, while three patients (15%) had Grade ≥2 pneumonitis/RP within 3 months after durvalumab initiation. Three months after durvalumab initiation, all the patients were alive and four patients (20%) experienced disease progression. Conclusion Durvalumab can be a feasible treatment option for patients with stage III NSCLC with baseline Grade 1 RP following CCRT.(Trial registration number: UMIN000036061. The registration period was between March 2019 and December 2019.).
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- 2021
16. Factors Influencing Social Isolation and Loneliness Among Lung Cancer Patients: A Cross-sectional Study
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Masatoshi Shimada, Emiko Saito, Takuma Imakita, Nobuko Wada, Masataka Hirabayashi, Hirohito Takata, Reika Iki, Koya Okazaki, Chigusa Shirakawa, Sawako Kaku, Takehiro Otoshi, Nanami Ashi, Kazuo Endo, Tomoyasu Takemura, Katsuya Hirano, Junichi Nikaido, Toru Naganuma, Hirotaka Matsumoto, Yuki Kataoka, Azusa Sakurai, Shunkichi Ikegaki, Mariko Shinomiya, and Tomoyuki Hirai
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Adult ,Male ,Gerontology ,Cancer Research ,Lung Neoplasms ,Cross-sectional study ,media_common.quotation_subject ,Care provision ,medicine ,Humans ,Dementia ,Social determinants of health ,Social isolation ,Aged ,media_common ,Aged, 80 and over ,business.industry ,Loneliness ,General Medicine ,Middle Aged ,medicine.disease ,UCLA Loneliness Scale ,Cross-Sectional Studies ,Social Isolation ,Oncology ,Female ,medicine.symptom ,business ,Welfare - Abstract
Background/aim Previous reviews of Social determinants of health in lung cancer patients have not examined essential factors such as social isolation and loneliness. This study aimed to explore the factors affecting social isolation and loneliness among lung cancer patients. Patients and methods A cross-sectional study was conducted. Social isolation, loneliness, and the presence of dementia were measured using Japanese adaptations of the Lubben Social Network Scale, UCLA Loneliness Scale, and Life Function Evaluation for Care Provision, respectively. Results From March 2019 to March 2020, 264 patients were included. Social isolation was significantly higher for patients receiving welfare (adjusted OR=5.28, 95% CI=2.24-12.4). Loneliness was significantly higher for patients receiving welfare (beta coefficient=0.52, 95% Cl=0.13-0.90) with symptoms of dementia (beta coefficient=0.28, 95% Cl=0.03-0.54). Conclusion Results showed that receiving welfare was associated with experiencing social isolation. Receiving welfare and symptoms of dementia were associated with experiencing loneliness.
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- 2020
17. Eicosapentaenoic acid ameliorates pulmonary hypertension via inhibition of tyrosine kinase Fyn
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Kaori Koga, Tetsuhiko Go, Mikiko Aoki, Ryuji Inoue, Hiroyasu Yokomise, Aya Yamamura, Kohtaro Abe, Katsuya Hirano, Lin Hai Kurahara, Narumi Aoki-Shoi, Sei Kobayashi, Eiji Yahiro, Satoh Toru, Hiroko Kishi, Keizo Hiraishi, Zhang Bo, Kaori Ishikawa, and Ying Zhang
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Male ,STAT3 Transcription Factor ,0301 basic medicine ,Hypertension, Pulmonary ,Myocytes, Smooth Muscle ,Pulmonary Artery ,030204 cardiovascular system & hematology ,Pharmacology ,SRC Family Tyrosine Kinase ,Proto-Oncogene Proteins c-fyn ,Mesoderm ,Rats, Sprague-Dawley ,Transforming Growth Factor beta2 ,03 medical and health sciences ,0302 clinical medicine ,FYN ,Animals ,Humans ,Medicine ,Phosphorylation ,STAT3 ,Molecular Biology ,Cell Proliferation ,Monocrotaline ,Hypertrophy, Right Ventricular ,Ventricular Remodeling ,biology ,Interleukin-6 ,business.industry ,Kinase ,Endothelial Cells ,medicine.disease ,Myocardial Contraction ,Survival Analysis ,Pulmonary hypertension ,Vasodilation ,src-Family Kinases ,030104 developmental biology ,Eicosapentaenoic Acid ,biology.protein ,Endothelium, Vascular ,medicine.symptom ,Cardiology and Cardiovascular Medicine ,business ,Tyrosine kinase ,Vasoconstriction - Abstract
Pulmonary arterial hypertension (PAH) is a multifactorial disease characterized by pulmonary arterial vasoconstriction and remodeling. Src family tyrosine kinases, including Fyn, play critical roles in vascular remodeling via the inhibition of STAT3 signaling. EPA is known to inhibit Fyn kinase activity. This study investigated the therapeutic potential and underlying mechanisms of EPA and its metabolite, resolvin E1 (RvE1), to treat PAH using monocrotaline-induced PAH model rats (MCT-PAH), human pulmonary artery endothelial cells (HPAECs), and human pulmonary artery smooth muscle cells (HPASMCs). Administration of EPA 1 and 2 weeks after MCT injection both ameliorated right ventricular hypertrophy, remodeling and dysfunction, and medial wall thickening of the pulmonary arteries and prolonged survival in MCT-PAH rats. EPA attenuated the enhanced contractile response to 5-hydroxytryptamine in isolated pulmonary arteries of MCT-PAH rats. Mechanistically, the treatment with EPA and RvE1 or the introduction of dominant-negative Fyn prevented TGF-β2-induced endothelial-to-mesenchymal transition and IL-6-induced phosphorylation of STAT3 in cultured HPAECs. EPA and RvE1 suppressed Src family kinases' activity as evaluated by their phosphorylation status in cultured HPAECs and HPASMCs. EPA and RvE1 suppressed vasocontraction of rat and human PA. Furthermore, EPA and RvE1 inhibited the enhanced proliferation and activity of Src family kinases in HPASMCs derived from patients with idiopathic PAH. EPA ameliorated PAH's pathophysiology by mitigating vascular remodeling and vasoconstriction, probably inhibiting Src family kinases, especially Fyn. Thus, EPA is considered a potent therapeutic agent for the treatment of PAH.
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- 2020
18. Bevacizumab plus cisplatin/pemetrexed then bevacizumab alone for unresectable malignant pleural mesothelioma: A Japanese safety study
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Misa Tanaka, Masahiro Morise, Masashi Kondo, Kozo Kuribayashi, Morihiko Hayashi, Katsuya Hirano, Masataka Hirabayashi, Yuji Tada, and Takashi Nakano
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safety ,Male ,Oncology ,medicine.medical_specialty ,Bevacizumab ,Nausea ,Pleural Neoplasms ,cisplatin ,Pemetrexed ,bevacizumab ,Malignancy ,03 medical and health sciences ,0302 clinical medicine ,Japan ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,malignant pleural mesothelioma ,Humans ,030212 general & internal medicine ,Adverse effect ,Aged ,Cisplatin ,business.industry ,Mesothelioma, Malignant ,Original Articles ,General Medicine ,Middle Aged ,Prognosis ,medicine.disease ,Regimen ,Tolerability ,030220 oncology & carcinogenesis ,Original Article ,Female ,medicine.symptom ,business ,medicine.drug - Abstract
Aims Malignant pleural mesothelioma (MPM) is an aggressive malignancy with poor prognosis and limited treatment options. Cisplatin plus pemetrexed is the only approved first‐line treatment for patients with unresectable MPM. Recently, promising outcomes were observed with first‐line bevacizumab combined with cisplatin/pemetrexed, leading to the recommendation of this regimen as a first‐line treatment option for patients with MPM. Bevacizumab plus cisplatin/pemetrexed has been shown to be safe and effective in non–small cell lung cancer, however, there are no efficacy or safety data in Japanese patients with MPM treated with this regimen. We conducted a multicenter study to evaluate tolerability and safety for Japanese patients with chemotherapy‐naïve, unresectable MPM. Methods Eligible patients (n = 7) received bevacizumab plus cisplatin/pemetrexed (up to six cycles), then single‐agent bevacizumab until disease progression or onset of unacceptable adverse events (AEs), according to the 3+3 design analogy. Results One patient (14.3%) reported an AE (gastric ulcer) meeting tolerability criteria. All patients experienced gastrointestinal disorders, including nausea (grade 1/2 only, n = 6, 85.7%) and constipation (grade 1/2 only, n = 5, 71.4%). Five patients (71.4%) had grade 3 hypertension. Two patients discontinued treatment due to gastric ulcer (n = 1) and proteinuria (n = 1). At data cut‐off, four patients had stable disease, two had partial response and one had non‐complete response/non‐progressive disease due to the absence of target lesions. Conclusions Bevacizumab plus cisplatin/pemetrexed then bevacizumab was well tolerated in Japanese patients with MPM., The addition of bevacizumab to standard cisplatin/pemetrexed showed survival benefit in mesothelioma patients, leading to its recommendation as a first‐line treatment option. Until now, there have been no tolerability or safety data for the triplet combination in Japanese mesothelioma patients. We evaluated this triplet combination for Japanese mesothelioma patients in a clinical trial according to the 3+3 design analogy and demonstrated its safety and tolerability.
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- 2020
19. Treatment Rationale and Design for APPLE (WJOG11218L): A Multicenter, Open-Label, Randomized Phase 3 Study of Atezolizumab and Platinum/Pemetrexed With or Without Bevacizumab for Patients With Advanced Nonsquamous Non–Small-Cell Lung Cancer
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Haruko Daga, Junji Kishimoto, Shunichi Sugawara, Osamu Hataji, Hidetoshi Hayashi, Yoshimasa Shiraishi, Katsuya Hirano, Koichi Azuma, Motoko Tachihara, Takashi Seto, Kazuhiko Nakagawa, Nobuyuki Yamamoto, Isamu Okamoto, Tetsuya Mitsudomi, and Kentaro Tanaka
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Adult ,Male ,0301 basic medicine ,Pulmonary and Respiratory Medicine ,Oncology ,Cancer Research ,medicine.medical_specialty ,Lung Neoplasms ,Bevacizumab ,Combination therapy ,Adenocarcinoma of Lung ,Pemetrexed ,Antibodies, Monoclonal, Humanized ,Carboplatin ,Young Adult ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Maintenance therapy ,Atezolizumab ,Carcinoma, Non-Small-Cell Lung ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Humans ,Progression-free survival ,Aged ,Aged, 80 and over ,Performance status ,business.industry ,Middle Aged ,Prognosis ,030104 developmental biology ,chemistry ,Research Design ,030220 oncology & carcinogenesis ,Female ,business ,medicine.drug - Abstract
Background First-line treatment of non–small-cell lung cancer (NSCLC) has undergone a paradigm shift to platinum combination therapy together with an immune checkpoint inhibitor (ICI). Bevacizumab is expected to enhance not only chemotherapy but also the efficacy of ICIs through blockade of vascular endothelial growth factor–mediated immunosuppression. We have now designed a randomized phase 3 study (APPLE, WJOG11218L, JapicCTI-194565) to evaluate the additional effect of bevacizumab administered together with platinum combination therapy and the ICI atezolizumab in patients with advanced nonsquamous NSCLC. Patients and Methods Cytotoxic chemotherapy–naive patients aged 20 years or older with a performance status of 0 or 1 are randomly assigned in a 1:1 ratio to receive either atezolizumab plus pemetrexed/carboplatin or atezolizumab, pemetrexed/carboplatin, and bevacizumab. Patients with genetic driver alterations such as those affecting EGFR or ALK are included if they have experienced disease progression or unacceptable adverse effects during treatment with at least one approved tyrosine kinase inhibitor. After 4 cycles of induction therapy, maintenance therapy with atezolizumab plus pemetrexed or with atezolizumab, pemetrexed, and bevacizumab is administered for up to 2 years until evidence of disease progression or development of unacceptable toxicity. The primary end point is progression-free survival. Conclusion This is a phase 3 study to investigate the effect of adding bevacizumab to an ICI and platinum/pemetrexed combination therapy. If the primary objective is achieved, this study will provide a new standard treatment for cytotoxic chemotherapy–naive patients with advanced nonsquamous NSCLC.
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- 2020
20. PURPOSE OF SEAWALLS IN MIYAGI PREFECTURE’S TSUNAMI COUNTERMEASURES PLANNED AFTER THE SANRIKU TSUNAMI OF 1933
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Chise NISHIWAKI, Makoto OKUMURA, and Katsuya HIRANO
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General Medicine - Published
- 2023
21. Toward Easy and Rapid Bronchial Occlusion With an Endobronchial Watanabe Spigot
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Tetsuji Kawamura, Yasuharu Nakahara, Nobuya Hirata, Rinko Katsuda, Ryota Hiraoka, Kohei Miyake, Yasuyuki Mizumori, Katsuya Hirano, Kenji Hanaoka, and Ryota Kominami
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Male ,Pulmonary and Respiratory Medicine ,Hemoptysis ,medicine.medical_specialty ,medicine.medical_treatment ,Operative Time ,Bronchopleural fistula ,03 medical and health sciences ,Postoperative Complications ,0302 clinical medicine ,Bronchoscopy ,medicine ,Humans ,030212 general & internal medicine ,Embolization ,Flexible bronchoscopy ,Aged ,Procedure time ,Aged, 80 and over ,Bronchus ,Curette ,business.industry ,Pneumothorax ,Bronchial Diseases ,Equipment Design ,Bronchial occlusion ,Middle Aged ,Pleural Diseases ,respiratory system ,Surgical Instruments ,medicine.disease ,Embolization, Therapeutic ,respiratory tract diseases ,Surgery ,Treatment Outcome ,medicine.anatomical_structure ,030228 respiratory system ,Female ,Bronchial Fistula ,business ,Upper lobe bronchus - Abstract
Background Bronchial occlusion using an endobronchial Watanabe spigot (EWS) is reportedly effective for intractable bronchopleural fistula. Here, we describe a rapid and easy method for bronchial occlusion using a guide sheath (GS) and curette. Methods Thirty consecutive patients who underwent bronchial occlusion under mild sedation between October 2014 and February 2018 were enrolled. The devices used were a flexible bronchoscope (BF-1T260 or BF-1TQ290), GS (SG-201C; with 30 mm of the proximal end cutaway), and a CC-4CR-1 curette (all supplied by Olympus Ltd). The curette was inserted into the GS with the tip of the curette exposed outside the GS. The curette and GS were inserted into the bronchoscope. The EWS attached to the curette tip was inserted into the target bronchus and left in position by pulling the curette back through the GS while pushing the EWS with the GS under the bronchoscopic view. The success rate and procedure time were recorded. Results Bronchial occlusion with an EWS was performed on 143 target bronchi (2 to 9 bronchi/patient). The bronchial occlusion success rate was 98.6%. The median procedure time for bronchial occlusion per EWS on video recordings of the 10 most recent procedures was 110 (range, 40 to 521) seconds. The target bronchial occlusion success rate was 100%. This method enabled easy insertion of the EWS, even in the sharply branching upper lobe bronchus. No complications were observed. Conclusion Bronchial occlusion using a GS and curette is a rapid and easy technique even in a sharply branching target bronchus.
- Published
- 2019
22. Ramucirumab plus erlotinib in patients with untreated, EGFR-mutated, advanced non-small-cell lung cancer (RELAY): a randomised, double-blind, placebo-controlled, phase 3 trial
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Kazuhiko Nakagawa, Edward B Garon, Takashi Seto, Makoto Nishio, Santiago Ponce Aix, Luis Paz-Ares, Chao-Hua Chiu, Keunchil Park, Silvia Novello, Ernest Nadal, Fumio Imamura, Kiyotaka Yoh, Jin-Yuan Shih, Kwok Hung Au, Denis Moro-Sibilot, Sotaro Enatsu, Annamaria Zimmermann, Bente Frimodt-Moller, Carla Visseren-Grul, Martin Reck, Quincy Chu, Alexis Cortot, Jean-Louis Pujol, Elizabeth Fabre, Corinne Lamour, Helge Bischoff, Jens Kollmeier, Martin Kimmich, Walburga Engel-Riedel, Stefan Hammerschmidt, Wolfgang Schütte, Konstantinos Syrigos, James Chung Man Ho, Kwok-Hung Au, Andrea Ardizzoni, Giulia Pasello, Vanessa Gregorc, Alessandro Del Conte, Domenico Galetta, Toshiaki Takahashi, Toru Kumagai, Katsuyuki Hotta, Yasushi Goto, Yukio Hosomi, Hiroshi Sakai, Yuichi Takiguchi, Young Hak Kim, Takayasu Kurata, Hiroyuki Yamaguchi, Haruko Daga, Isamu Okamoto, Miyako Satouchi, Satoshi Ikeda, Kazuo Kasahara, Shinji Atagi, Koichi Azuma, Keisuke Aoe, Yoshitsugu Horio, Nobuyuki Yamamoto, Hiroshi Tanaka, Satoshi Watanabe, Naoyuki Nogami, Tomohiro Ozaki, Ryo Koyama, Tomonori Hirashima, Hiroyasu Kaneda, Keisuke Tomii, Yuka Fujita, Masahiro Seike, Naoki Nishimura, Terufumi Kato, Masao Ichiki, Hideo Saka, Katsuya Hirano, Yasuharu Nakahara, Shunichi Sugawara, Sang-We Kim, Young Joo Min, Hyun Woo Lee, Jin-Hyoung Kang, Ho Jung An, Ki Hyeong Lee, Jin-Soo Kim, Gyeong-Won Lee, Sung Yong Lee, Aurelia Alexandru, Anghel Adrian Udrea, Óscar Juan-Vidal, Ernest Nadal-Alforja, Ignacio Gil-Bazo, Santiago Ponce-Aix, Belén Rubio-Viqueira, Miriam Alonso Garcia, Enriqueta Felip Font, Jose Fuentes Pradera, Juan Coves Sarto, Meng-Chih Lin, Wu-Chou Su, Te-Chun Hsia, Gee-Chen Chang, Yu-Feng Wei, Jian Su, Irfan Cicin, Tuncay Goksel, Hakan Harputluoglu, Ozgur Ozyilkan, Ivo Henning, Sanjay Popat, Olivia Hatcher, Kathryn Mileham, Jared Acoba, Edward Garon, Gabriel Jung, Moses Raj, William Martin, and Shaker Dakhil
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Male ,0301 basic medicine ,Oncology ,medicine.medical_specialty ,Lung Neoplasms ,Population ,Adenocarcinoma of Lung ,Antibodies, Monoclonal, Humanized ,Placebo ,Antibodies ,Ramucirumab ,Erlotinib Hydrochloride ,03 medical and health sciences ,0302 clinical medicine ,Double-Blind Method ,Carcinoma, Non-Small-Cell Lung ,Internal medicine ,Monoclonal ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Humans ,Non-Small-Cell Lung ,Lung cancer ,education ,Humanized ,Survival rate ,Aged ,education.field_of_study ,business.industry ,Carcinoma ,Middle Aged ,Prognosis ,medicine.disease ,ErbB Receptors ,Female ,Follow-Up Studies ,Survival Rate ,Mutation ,respiratory tract diseases ,Regimen ,030104 developmental biology ,030220 oncology & carcinogenesis ,Erlotinib ,business ,medicine.drug - Abstract
Dual blockade of the EGFR and VEGF pathways in EGFR-mutated metastatic non-small-cell lung cancer (NSCLC) is supported by preclinical and clinical data, yet the approach is not widely implemented. RELAY assessed erlotinib, an EGFR tyrosine kinase inhibitor (TKI) standard of care, plus ramucirumab, a human IgG1 VEGFR2 antagonist, or placebo in patients with untreated EGFR-mutated metastatic NSCLC.This is a worldwide, double-blind, phase 3 trial done in 100 hospitals, clinics, and medical centres in 13 countries. Eligible patients were aged 18 years or older (20 years or older in Japan and Taiwan) at the time of study entry, had stage IV NSCLC, with an EGFR exon 19 deletion (ex19del) or exon 21 substitution (Leu858Arg) mutation, an Eastern Cooperative Oncology Group performance status of 0 or 1, and no CNS metastases. We randomly assigned eligible patients in a 1:1 ratio to receive oral erlotinib (150 mg/day) plus either intravenous ramucirumab (10 mg/kg) or matching placebo once every 2 weeks. Randomisation was done by an interactive web response system with a computer-generated sequence and stratified by sex, geographical region, EGFR mutation type, and EGFR testing method. The primary endpoint was investigator-assessed progression-free survival in the intention-to-treat population. Safety was assessed in all patients who received at least one dose of study treatment. This trial is registered at ClinicalTrials.gov, NCT02411448, and is ongoing for long-term survival follow-up.Between Jan 28, 2016, and Feb 1, 2018, 449 eligible patients were enrolled and randomly assigned to treatment with ramucirumab plus erlotinib (n=224) or placebo plus erlotinib (n=225). Median duration of follow-up was 20·7 months (IQR 15·8-27·2). At the time of primary analysis, progression-free survival was significantly longer in the ramucirumab plus erlotinib group (19·4 months [95% CI 15·4-21·6]) than in the placebo plus erlotinib group (12·4 months [11·0-13·5]), with a stratified hazard ratio of 0·59 (95% CI 0·46-0·76; p0·0001). Grade 3-4 treatment-emergent adverse events were reported in 159 (72%) of 221 patients in the ramucirumab plus erlotinib group versus 121 (54%) of 225 in the placebo plus erlotinib group. The most common grade 3-4 treatment-emergent adverse events in the ramucirumab plus erlotinib group were hypertension (52 [24%]; grade 3 only) and dermatitis acneiform (33 [15%]), and in the placebo plus erlotinib group were dermatitis acneiform (20 [9%]) and increased alanine aminotransferase (17 [8%]). Treatment-emergent serious adverse events were reported in 65 (29%) of 221 patients in the ramucirumab plus erlotinib group and 47 (21%) of 225 in the placebo plus erlotinib group. The most common serious adverse events of any grade in the ramucirumab plus erlotinib group were pneumonia (seven [3%]) and cellulitis and pneumothorax (four [2%], each); the most common in the placebo plus erlotinib group were pyrexia (four [2%]) and pneumothorax (three [1%]). One on-study treatment-related death due to an adverse event occurred (haemothorax after a thoracic drainage procedure for a pleural empyema) in the ramucirumab plus erlotinib group.Ramucirumab plus erlotinib demonstrated superior progression-free survival compared with placebo plus erlotinib in patients with untreated EGFR-mutated metastatic NSCLC. Safety was consistent with the safety profiles of the individual compounds in advanced lung cancer. The RELAY regimen is a viable new treatment option for the initial treatment of EGFR-mutated metastatic NSCLC.Eli Lilly.
- Published
- 2019
23. Association between metastatic sites and first-line pembrolizumab treatment outcome for advanced non–small cell lung cancer with high PD-L1 expression: a retrospective multicenter cohort study
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Akihiro Tamiya, Tomonori Hirashima, Nobuhiko Sawa, Ryota Kominami, Toshihide Yokoyama, Hidekazu Suzuki, Daichi Fujimoto, Junji Uchida, Masaki Kanazu, Satoshi Hara, Hirotaka Matsumoto, Kazutaka Hosoya, Mitsunori Morita, Hayato Kawachi, Yasushi Fukuda, Motohiro Tamiya, Takeshi Makio, Toru Kumagai, Katsuya Hirano, and Seigo Ishii
- Subjects
Adult ,Male ,0301 basic medicine ,Oncology ,medicine.medical_specialty ,Lung Neoplasms ,Pembrolizumab ,Adenocarcinoma ,Antibodies, Monoclonal, Humanized ,B7-H1 Antigen ,Metastasis ,03 medical and health sciences ,Antineoplastic Agents, Immunological ,0302 clinical medicine ,Carcinoma, Non-Small-Cell Lung ,Internal medicine ,Biomarkers, Tumor ,Humans ,Medicine ,Malignant pleural effusion ,Pharmacology (medical) ,Lung cancer ,Response Evaluation Criteria in Solid Tumors ,Aged ,Retrospective Studies ,Aged, 80 and over ,Pharmacology ,business.industry ,Hazard ratio ,Bone metastasis ,Retrospective cohort study ,Middle Aged ,Prognosis ,medicine.disease ,Survival Rate ,030104 developmental biology ,030220 oncology & carcinogenesis ,Carcinoma, Squamous Cell ,Female ,business ,Follow-Up Studies - Abstract
Associations between treatment outcomes of immune checkpoint inhibitors and metastatic sites in advanced non-small cell lung cancer (NSCLC) are not well known. Therefore, this multicenter retrospective study aimed to investigate the predictive factors of metastatic sites after first-line pembrolizumab treatment for advanced NSCLC with a PD-L1 tumor proportion score (TPS) ≥50%. We retrospectively analyzed advanced NSCLC patients with a PD-L1 TPS ≥50% who underwent first-line pembrolizumab therapy at 11 institutions between February 2017 and April 2018. Clinical data collected from medical records included metastatic sites at the time of pembrolizumab treatment. Treatment outcomes of pembrolizumab were assessed according to the Response Evaluation Criteria in Solid Tumors, version 1.1. In total, 213 patients were included in the study. The median age was 71 years (range 39-91 years). Of the 213 patients, 176 (83%) were men and 172 (81%) had an Eastern Cooperative Oncology Group performance status (ECOG-PS) score of 0-1. The most common metastases were thoracic lymph node metastasis (77%), intrapulmonary metastasis (31%), bone metastasis (28%), and malignant pleural effusion (26%). On multivariate analysis, a poor ECOG-PS score (hazard ratio: 1.95, 95.0% confidence interval: 1.25-3.04; P = 0.003) and malignant pleural effusion (hazard ratio: 1.52, 95.0% confidence interval: 1.01-2.29; P = 0.043) were independent predictors of shorter progression-free survival in patients treated with pembrolizumab. For NSCLC patients with malignant pleural effusion, pembrolizumab monotherapy is not a suitable first-line treatment because of its insufficient effectiveness, even though their PD-L1 TPS was high.
- Published
- 2019
24. RELAY+: Exploratory Study of Ramucirumab Plus Gefitinib in Untreated Patients With
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Makoto, Nishio, Kazuto, Nishio, Martin, Reck, Edward B, Garon, Fumio, Imamura, Tomoya, Kawaguchi, Hiroyuki, Yamaguchi, Satoshi, Ikeda, Katsuya, Hirano, Carla, Visseren-Grul, Matteo, Ceccarelli, Sameera R, Wijayawardana, Annamaria, Zimmermann, Tomoko, Matsui, Sotaro, Enatsu, and Kazuhiko, Nakagawa
- Abstract
Ramucirumab (RAM) plus erlotinib was found to have superior progression-free survival (PFS) versus placebo plus erlotinib in untreatedPeriod 1 evaluated RAM (10 mg/kg) plus GEF (250 mg/d) in patients with untreatedFrom December 2017 to August 2018, a total of 82 patients were enrolled and started treatment (period 1, RAM + GEF). The 1-year PFS rate was 62.9% (95% confidence interval: 50.3-73.1). Treatment-emergent adverse events of grade three or higher were reported with RAM plus GEF in 60 of 82 patients (73.2%; five patients [6.1%] grade four). There were two deaths owing to adverse events that occurred (acute cardiac failure, congestive cardiac failure). T790M rate at disease progression in plasma was 81.0% (13 of 16 patients).RELAY+ was found to have a favorable benefit-risk profile for RAM plus GEF in first-line treatment of East Asian patients with
- Published
- 2021
25. Alternating therapy with osimertinib and afatinib for treatment-naive patients with EGFR-mutated advanced non-small cell lung cancer: A single-group, open-label phase 2 trial (WJOG10818L)
- Author
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Hidetoshi Hayashi, Kimio Yonesaka, Atsushi Nakamura, Daichi Fujimoto, Koichi Azuma, Shinya Sakata, Motoko Tachihara, Satoshi Ikeda, Toshihide Yokoyama, Osamu Hataji, Yukihiro Yano, Katsuya Hirano, Haruko Daga, Hideaki Okada, Yasutaka Chiba, Kazuko Sakai, Kazuto Nishio, Nobuyuki Yamamoto, and Kazuhiko Nakagawa
- Subjects
Pulmonary and Respiratory Medicine ,Cancer Research ,Acrylamides ,Aniline Compounds ,Indoles ,Lung Neoplasms ,Antineoplastic Agents ,Genes, erbB-1 ,Afatinib ,ErbB Receptors ,Pyrimidines ,Oncology ,Carcinoma, Non-Small-Cell Lung ,Mutation ,Humans - Abstract
Alternation of osimertinib and afatinib is a potential approach to overcome osimertinib resistance and to allow complementation of drug efficacy without compromising safety in patients with epidermal growth factor receptor gene (EGFR)-mutated non-small cell lung cancer (NSCLC).Treatment-naive patients with stage IV NSCLC harboring an activating EGFR mutation (L858R or exon-19 deletion) were enrolled. Alternating cycles of osimertinib at 80 mg/day for 8 weeks followed by afatinib at 20 mg/day for 8 weeks were administered. The primary end point was 12-month progression-free survival (PFS) probability.Forty-six patients were enrolled and treated with study therapy. The 12-month PFS probability was 70.2% (60% confidence interval [CI], 63.9-75.6%; 95% CI, 54.2-81.5%), which did not meet the primary end point. After a median follow-up time of 25.7 months, the median PFS was 21.3 months (95% CI, 16.3 months-not reached). The overall response rate was 69.6% (95% CI, 54.2-82.3%). The most common treatment-related adverse events (any grade or grade ≥ 3, respectively) were diarrhea (73.9%, 4.3%), rash acneiform (63.0%, 2.2%), and paronychia (52.2%, 0%). Five cases of pneumonitis, two of grade 2 and thres of grade 3, were apparent, all of which developed during osimertinib treatment. Exploratory evaluation of circulating tumor DNA suggested that coexisting TP53 mutations did not influence PFS for the alternating therapy.Alternating therapy with osimertinib and afatinib for treatment-naive patients with EGFR- mutated advanced NSCLC did not meet its primary end point, despite the encouraging efficacy and safety profile of this treatment strategy.
- Published
- 2021
26. Hokkaidō 150: settler colonialism and Indigeneity in modern Japan and beyond
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Tristan R. Grunow, Sheryl Lightfoot, Fuyubi Nakamura, Danika Medak-Saltzman, Mayunkiki, Katsuya Hirano, Terri-Lynn Williams-Davidson, Mai Ishihara, ann-elise lewallen, and Tomoe Yahata
- Subjects
History ,Sociology and Political Science ,Anthropology ,Geography, Planning and Development ,Colonialism - Abstract
This roundtable presents the proceedings of the “Hokkaidō 150: Settler Colonialism and Indigeneity in Modern Japan and Beyond” workshop held at the University of British Columbia in March 2019. The...
- Published
- 2019
27. Evaluation of Microorganisms of Humidifier Water and Humidified Air in Home Humidifier
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Ryota Hiraoka, Sachiko Higashino, Yasutaka Onishi, Shin Sasaki, Sachie Kume, Sayaka Takahashi, Tetsuji Kawamura, Hiroko Tanaka, Nobuya Hirata, Katsuya Hirano, Ryota Kominami, Hiroaki Tsukamoto, Shoma Mizuno, Masaki Takenouchi, and Yasuharu Nakahara
- Subjects
Humidifier water ,Waste management ,Microorganism ,Environmental science - Published
- 2019
28. Efficacy and safety of pembrolizumab as first-line therapy in advanced non-small cell lung cancer with at least 50% PD-L1 positivity: a multicenter retrospective cohort study (HOPE-001)
- Author
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Toru Kumagai, Masaki Kanazu, Daichi Fujimoto, Akihiro Tamiya, Hirotaka Matsumoto, Toshihide Yokoyama, Junji Uchida, Satoshi Hara, Mitsunori Morita, Yoshihiko Taniguchi, Motohiro Tamiya, Nobuhiko Sawa, Ryota Kominami, Kazutaka Hosoya, Yoshinori Kinoshita, Katsuya Hirano, Hidekazu Suzuki, Tomonori Hirashima, and Yasushi Fukuda
- Subjects
Adult ,Male ,0301 basic medicine ,medicine.medical_specialty ,Lung Neoplasms ,Pembrolizumab ,Antibodies, Monoclonal, Humanized ,Gastroenterology ,B7-H1 Antigen ,03 medical and health sciences ,Antineoplastic Agents, Immunological ,0302 clinical medicine ,Carcinoma, Non-Small-Cell Lung ,Internal medicine ,medicine ,Carcinoma ,Humans ,Pharmacology (medical) ,Progression-free survival ,Lung cancer ,Adverse effect ,Aged ,Pneumonitis ,Aged, 80 and over ,Pharmacology ,Predictive marker ,business.industry ,Retrospective cohort study ,Middle Aged ,medicine.disease ,Treatment Outcome ,030104 developmental biology ,Oncology ,030220 oncology & carcinogenesis ,Female ,business - Abstract
Objectives As first line therapy, pembrolizumab provides longer progression free survival (PFS) and overall survival (OS) than platinum doublets in programmed death ligand 1 (PD-L1)-positive non-small cell lung cancer (NSCLC) with tumor propensity scores (TPS) ≥50%. However, clinical trials do not represent real-world patients. Materials and Methods This multicenter retrospective study conducted across 11 medical centers in Japan analyzed clinical data from patients receiving first-line pembrolizumab for NSCLC between February 1, 2017 and April 30, 2018. The efficacy, safety, and suitability of pembrolizumab monotherapy were evaluated. Results The median age of the 213 enrolled patients was 71 (range: 39–91) years. Among them, 176 (82.6%) were male, 20 (9.4%) were never smokers (median Brinkman index: 900), 172 (80.8%) had an ECOG PS of 0–1, 55 (25.8%) had squamous-cell carcinoma (SQ). PD-L1 TPS were 50–74%, 75–89%, and 90–100% in 97 (45.5%), 47 (22.1%), and 69 (32.4%) patients, respectively. Adverse events (AEs) of grades ≥3 were observed in 39 (18.3%) patients. Pneumonitis was the most common severe AE, occurring in 10 patients (4.7%) including 1 with grade 4 toxicity; no severe AE-related deaths occurred. The overall response rate, median PFS, and median OS was 51.2%, 8.3 months, and 17.8 months, respectively. On multivariate analysis, ECOG PS (0–1 vs. ≥2: HR: 1.69, 95.0% CI: 1.05–2.72; p = 0.03138), CRP/Alb (
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- 2019
29. Coagulation factor XI induces Ca2+response and accelerates cell migration in vascular smooth muscle cells via proteinase-activated receptor 1
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Katsuya Hirano, Tetsuo Yamashita, Wenhua Liu, and Takeshi Hashimoto
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0301 basic medicine ,Vascular smooth muscle ,Physiology ,Chemistry ,Activated coagulation factor ,Cell migration ,Cell Biology ,030204 cardiovascular system & hematology ,Cell biology ,Serine ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,Coagulation ,Coagulation factor XI ,Proteinase Activated Receptor 1 - Abstract
Activated coagulation factor XI (FXIa) is a serine proteinase that plays a key role in the intrinsic coagulation pathway. The analysis of FXI-knockout mice has indicated the contribution of FXI to the pathogenesis of atherosclerosis. However, the underlying mechanism remains unknown. We hypothesized that FXIa exerts vascular smooth muscle effects via proteinase-activated receptor 1 (PAR1). Fura-2 fluorometry revealed that FXIa elicited intracellular Ca2+signal in rat embryo aorta smooth muscle A7r5 cells. The influx of extracellular Ca2+played a greater role in generating Ca2+signal than the Ca2+release from intracellular stores. The FXIa-induced Ca2+signal was abolished by the pretreatment with atopaxar, an antagonist of PAR1, or 4-amidinophenylmethanesulfonyl fluoride (p-APMSF), an inhibitor of proteinase, while it was also lost in embryonic fibroblasts derived from PAR1−/−mice. FXIa cleaved the recombinant protein containing the extracellular region of PAR1at the same site (R45/S46) as that of thrombin, a canonical PAR1agonist. The FXIa-induced Ca2+influx was inhibited by diltiazem, an L-type Ca2+channel blocker, and by siRNA targeted to CaV1.2. The FXIa-induced Ca2+influx was also inhibited by GF109203X and rottlerin, inhibitors of protein kinase C. In a wound healing assay, FXIa increased the rate of cell migration by 2.46-fold of control, which was partly inhibited by atopaxar or diltiazem. In conclusion, FXIa mainly elicits the Ca2+signal via the PAR1/CaV1.2-mediated Ca2+influx and accelerates the migration in vascular smooth muscle cells. The present study provides the first evidence that FXIa exerts a direct cellular effect on vascular smooth muscle.
- Published
- 2019
30. STATION GRADE SYSTEM AND ITS OPERATION IN THE PRE-WAR RAILWAY IN JAPAN
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Katsuya Hirano and Yuhei Kato
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Engineering ,business.industry ,Grade system ,Operations management ,business - Published
- 2019
31. Auswirkungen der Rebiopsie auf die Prognose von Patienten mit fortgeschrittenem nicht kleinzelligem Bronchialkarzinom nach Behandlung mit epidermalem Wachstumsfaktor-Rezeptor-Tyrosinkinase-Hemmer: ein systematischer Überblick
- Author
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Katsuya Hirano, Toshiyuki Morisawa, Takuma Imakita, Yuki Kataoka, Hirotaka Matsumoto, and Azusa Sakurai
- Abstract
Hintergrund: Osimertinib, ein epidermaler Wachstumsfaktorrezeptor-Tyrosinkinasehemmer (Epidermal Growth Factor Receptor-Tyrosine-kinase Inhibitor, EGFR-TKI) der 3. Generation, ist mittlerweile die Standardtherapie in Fällen, in denen die Rebiopsie nach der Erstlinienbehandlung mit EGFR-TKI eine T790M-Mutation ergibt. Die Prognose der Patienten nach Rebiopsie, dem wichtigsten Outcome bei Krebspatienten, wurde bislang jedoch nicht ausreichend beschrieben. Die vorliegende systematische Übersichtsarbeit sollte klären, ob die Rebiopsie bei Patienten, die gegenüber den EGFR-TKI der 1. und 2. Generation refraktär sind, zu einer verbesserten Prognose beiträgt. Methoden: Mithilfe freier Wort- und Kontrollbegriffe im Zusammenhang mit «nicht kleinzelligem Bronchialkarzinom» und «Rebiopsie» suchten wir Studien aus dem Medical Literature Analysis and Retrieval System Online über PubMed, Embase, Cochrane Central Register of Controlled Trials und die World Health Organization International Clinical Trials Registry Platform. Eingeschlossen wurden Kohortenstudien und Fallberichte in englischer Sprache und es erfolgte eine Beurteilung, ob die jeweilige Studie unsere wissenschaftliche Fragestellung beantwortete. Ergebnisse: Von den 144 eingeschlossenen Studien enthielt nur eine Studie Angaben zur Prognose von Patienten mit/ohne Rebiopsie und zeigte, dass bei EGFR-TKI-refraktären Patienten mit nicht kleinzelligem Bronchialkarzinom das Überleben nach Krankheitsprogression (post-progression survival, PPS) bei Patienten, die eine Rebiopsie sowie eine Behandlung entsprechend dem Resistenzmechanismus erhalten hatten, signifikant länger war (medianes PPS: 24,2 Monate) als bei Patienten die eine Rebiopsie und Salvage-Therapie erhalten hatten (medianes PPS: 15,2 Monate, p = 0,002) und solchen ohne Rebiopsie (medianes PPS: 9,7 Monate, p < 0,001). Die meisten anderen Studien berichteten über die Nachweisrate von T790M-Mutationen oder das Rebiopsieverfahren. Schlussfolgerungen: Nur wenige der bisher durchgeführten Studien untersuchten die Wirksamkeit der Rebiopsie. Daher sind weitere Untersuchungen erforderlich, um die Prognose oder Nebenwirkungen der Rebiopsie zu ermitteln.
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- 2019
32. A STUDY ON CHARACTERISTICS OF EVALUATION OF LANDSCAPE CONTAINING WIND TURBINES FOCUSING ON SCHEMA
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Katsuya Hirano, Hiroki Takagi, and Hirotoshi Shirayanagi
- Subjects
Wind power ,Computer science ,business.industry ,Schema (psychology) ,Systems engineering ,business - Published
- 2019
33. Proteinase-activated receptor 1 antagonism ameliorates experimental pulmonary hypertension
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Katsuya Hirano, Yoshitaka Hirooka, Yukimitsu Kuwabara, Kenji Sunagawa, Mayumi Hirano, Mariko Tanaka-Ishikawa, Hiroyuki Tsutsui, and Kohtaro Abe
- Subjects
Male ,0301 basic medicine ,Agonist ,Pyridines ,Physiology ,medicine.drug_class ,Hypertension, Pulmonary ,Pulmonary Artery ,Vascular Remodeling ,030204 cardiovascular system & hematology ,Pharmacology ,Ventricular Function, Left ,Vascular remodelling in the embryo ,Rats, Sprague-Dawley ,03 medical and health sciences ,0302 clinical medicine ,Right ventricular hypertrophy ,Physiology (medical) ,medicine.artery ,Animals ,Medicine ,Arterial Pressure ,Receptor, PAR-1 ,Antihypertensive Agents ,Mice, Knockout ,Monocrotaline ,Lung ,Hypertrophy, Right Ventricular ,Ventricular Remodeling ,business.industry ,Thrombin ,Hypoxia (medical) ,medicine.disease ,Pulmonary hypertension ,Disease Models, Animal ,030104 developmental biology ,medicine.anatomical_structure ,Pulmonary artery ,cardiovascular system ,Vascular resistance ,Imines ,medicine.symptom ,Cardiology and Cardiovascular Medicine ,business - Abstract
Aims Pulmonary hypertension (PH) is characterized by progressive increases in pulmonary vascular resistance (PVR). Thrombotic lesions are common pathological findings. The pulmonary artery has a unique property regarding the vasoconstrictive response to thrombin, which is mediated by proteinase-activated receptor 1 (PAR1). We aim to elucidate the role of PAR1 in the development and progression of PH. Methods and results A rat model of monocrotaline-induced PH and a mouse model of hypoxia (Hx)-induced PH were used to investigate the effects of atopaxar (a PAR1 antagonist) and PAR1 knockout on haemodynamic parameters, right ventricular hypertrophy (RVH), vascular remodelling and survival. In perfused lung preparations, the pressor response to PAR1 agonist was significantly augmented in monocrotaline-induced PH. Both the preventive and therapeutic administration of atopaxar significantly inhibited the increase in PVR and the development of RVH and prolonged survival. A real-time PCR revealed that the level of PAR1 mRNA in the pulmonary artery was significantly higher than that in any of the systemic arteries examined in control rats, and the level was significantly up-regulated in monocrotaline-induced PH. PAR1 gene knockout significantly attenuated the haemodynamic and histological findings in the mouse model of Hx-induced PH. Conclusion The specific expression of PAR1 in the pulmonary artery and its up-regulation were suggested to play a critical role in the development and progression of experimental PH in murine models. PAR1 is a potential therapeutic target for the treatment of PH.
- Published
- 2018
34. Chronic Inhibition of Toll‐Like Receptor 9 Ameliorates Pulmonary Hypertension in Rats
- Author
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Kazuya Hosokawa, Tomohito Ishikawa, Satomi Imakiire, Keimei Yoshida, Mayumi Hirano, Mariko Takana-Ishikawa, Hiroyuki Tsutsui, Takanori Watanabe, Kohtaro Abe, and Katsuya Hirano
- Subjects
Male ,vascular remodeling ,Hypertension, Pulmonary ,Hemodynamics ,Pulmonary Artery ,030204 cardiovascular system & hematology ,Pharmacology ,Vascular Medicine ,Rats, Sprague-Dawley ,Pathogenesis ,03 medical and health sciences ,0302 clinical medicine ,Pulmonary Biology ,pulmonary hypertension ,medicine ,Animals ,Receptor ,Interleukin 6 ,toll‐like receptor 9 ,Original Research ,030304 developmental biology ,Inflammation ,0303 health sciences ,Monocrotaline ,Lung ,biology ,business.industry ,TLR9 ,Chloroquine ,medicine.disease ,Pulmonary hypertension ,Rats ,perivascular inflammation ,Disease Models, Animal ,medicine.anatomical_structure ,interleukin‐6 ,Antirheumatic Agents ,Toll-Like Receptor 9 ,Ventricular pressure ,biology.protein ,Cardiology and Cardiovascular Medicine ,business - Abstract
Background Recent accumulating evidence suggests that toll‐like receptor 9 (TLR9) is involved in the pathogenesis of cardiovascular diseases. However, its role in pulmonary hypertension remains uncertain. We hypothesized that TLR9 is involved in the development of pulmonary hypertension. Methods and Results A rat model of monocrotaline‐induced pulmonary hypertension was used to investigate the effects of TLR9 on hemodynamic parameters, vascular remodeling, and survival. Monocrotaline‐exposed rats significantly showed increases in plasma levels of mitochondrial DNA markers, which are recognized by TLR9, TLR9 activation in the lung, and interleukin‐6 mRNA level in the lung on day 14 after monocrotaline injection. Meanwhile, monocrotaline‐exposed rats showed elevated right ventricular systolic pressure, total pulmonary vascular resistance index and vascular remodeling, together with macrophage accumulation on day 21. In the preventive protocol, administration (days −3 to 21 after monocrotaline injection) of selective (E6446) or nonselective TLR9 inhibitor (chloroquine) significantly ameliorated the elevations of right ventricular systolic pressure and total pulmonary vascular resistance index as well as vascular remodeling and macrophage accumulation on day 21. These inhibitors also significantly reduced NF‐κB activation and interleukin‐6 mRNA levels to a similar extent. In the short‐term reversal protocol, E646 treatment (days 14–17 after monocrotaline injection) almost normalized NF‐κB activation and interleukin‐6 mRNA level, and reduced macrophage accumulation. In the prolonged reversal protocol, E6446 treatment (days 14–24 after monocrotaline injection) reversed total pulmonary vascular resistance index and vascular remodeling, and improved survival in monocrotaline‐exposed rats. Conclusions TLR9 is involved in the development of pulmonary hypertension concomitant via activation of the NF‐κB‒IL‐6 pathway. Inhibition of TLR9 may be a novel therapeutic strategy for pulmonary hypertension.
- Published
- 2021
35. Inhibitory Effects of Breast Milk-Derived
- Author
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Haiyan, Xu, Keizo, Hiraishi, Lin-Hai, Kurahara, Yuko, Nakano-Narusawa, Xiaodong, Li, Yaopeng, Hu, Yoko, Matsuda, Heping, Zhang, and Katsuya, Hirano
- Subjects
Inflammation ,Male ,Milk, Human ,Carcinogenesis ,Lacticaseibacillus rhamnosus ,colitis-associated tumorigenesis ,Dextran Sulfate ,Neoplasms, Experimental ,Colitis ,Article ,Gastrointestinal Microbiome ,inflammatory bowel disease ,Lactobacillus rhamnosus M9 ,Colonic Neoplasms ,Humans ,probiotic - Abstract
Chronic inflammation is a risk factor for colorectal cancer, and inflammatory cytokines secreted from inflammatory cells and active oxygen facilitate tumorigenesis. Intestinal bacteria are thought to regulate tumorigenesis. The longer the breastfeeding period, the lower is the risk of inflammatory bowel disease. Here, we investigated preventive effects of the probiotic Lactobacillus rhamnosus M9 (Probio-M9) on colitis-associated tumorigenesis. An inflammatory colorectal tumor model was established using a 6-week-old male C57BL/6NCrSlc mouse, which was intraperitoneally administered with azoxymethane (AOM: 12 mg/kg body weight). On weeks 2 and 4, 2% dextran sulfate sodium (DSS) was administered to mice for 7 days through drinking water. On weeks 8 and 10, Probio-M9 (2 × 109/day) was orally administered for 7 days. Animals were sacrificed at 20 weeks after AOM administration and immunohistochemical staining and Western blotting was performed. The α-diversity of microflora (Shannon index), principal coordinate analysis, and distribution of intestinal bacterium genera and metabolic pathways were compared. The AOM/DSS group showed weight loss, diarrhea, intestinal shortening, increased number of colon tumors, proliferating tumorigenesis, increased inflammation score, fibrosis, increased CD68+, or CD163+ macrophage cells in the subserosal layer of non-tumor areas. Inflammation and tumorigenesis ameliorated after Probio-M9 treatment. Fecal microbial functions were altered by AOM/DSS treatment. Probio-M9 significantly upregulated the fecal microbial diversity and reversed fecal microbial functions. Thus, Probio-M9 could suppress tumor formation in the large intestine by regulating the intestinal environment and ameliorating inflammation, suggesting its therapeutic potential for treatment of inflammation and colitis-associated tumorigenesis.
- Published
- 2021
36. Vanishing Natives and Taiwan’s Settler-Colonial Unconscious
- Author
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Katsuya Hirano, Lorenzo Veracini, and Toulouse-Antonin Roy
- Published
- 2021
37. RELAY+: Exploratory Study of Ramucirumab Plus Gefitinib in Untreated Patients With EGFR-Mutated Metastatic NSCLC
- Author
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Makoto Nishio, Kazuto Nishio, Martin Reck, Edward B. Garon, Fumio Imamura, Tomoya Kawaguchi, Hiroyuki Yamaguchi, Satoshi Ikeda, Katsuya Hirano, Carla Visseren-Grul, Matteo Ceccarelli, Sameera R. Wijayawardana, Annamaria Zimmermann, Tomoko Matsui, Sotaro Enatsu, and Kazuhiko Nakagawa
- Subjects
Pulmonary and Respiratory Medicine ,Oncology - Published
- 2022
38. Phase 3 Trial Comparing Nanoparticle Albumin-Bound Paclitaxel With Docetaxel for Previously Treated Advanced NSCLC
- Author
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Tetsuya Oguri, Terufumi Kato, Junji Kishimoto, Masahiko Ando, Masafumi Takeshita, Yoichi Nakanishi, Shunichiro Iwasawa, Satoru Miura, Atsushi Nakamura, Toshiyuki Harada, Yasuhiro Goto, Hiroshige Yoshioka, Satoshi Morita, Katsuya Hirano, Isamu Okamoto, Yukio Hosomi, Yasuto Yoneshima, Nobuyuki Yamamoto, Masashi Kondo, and Toshio Kubo
- Subjects
0301 basic medicine ,Pulmonary and Respiratory Medicine ,medicine.medical_specialty ,Lung Neoplasms ,Paclitaxel ,Docetaxel ,Gastroenterology ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Internal medicine ,Albumins ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Clinical endpoint ,Humans ,Adverse effect ,business.industry ,Standard treatment ,medicine.disease ,Confidence interval ,030104 developmental biology ,Treatment Outcome ,Oncology ,chemistry ,030220 oncology & carcinogenesis ,Nanoparticles ,Albumin-Bound Paclitaxel ,Previously treated ,business ,Febrile neutropenia ,medicine.drug - Abstract
Introduction We aimed to evaluate the efficacy and safety of nanoparticle albumin-bound (nab-) paclitaxel for previously treated patients with advanced NSCLC. Methods In this randomized, open-label, noninferiority phase 3 trial, we enrolled patients with advanced NSCLC previously treated with cytotoxic chemotherapy. Patients were randomly allocated (1:1) to receive docetaxel (60 mg/m2) on day 1 or nab-paclitaxel (100 mg/m2) on days 1, 8, and 15 of a 21-day cycle. The primary end point was overall survival (OS) analyzed on an intention-to-treat basis. Results Between May 22, 2015, and March 12, 2018, a total of 503 patients were randomly allocated to the treatment. Median OS was 16.2 months (95% confidence interval [CI]: 14.4–19.0) for the 252 patients allocated to nab-paclitaxel and 13.6 months (95% CI: 10.9–16.5) for the 251 patients allocated to docetaxel (hazard ratio = 0.85, 95.2% CI: 0.68–1.07). Median progression-free survival was 4.2 months (95% CI: 3.9–5.0) for the nab-paclitaxel group versus 3.4 months (95% CI: 2.9–4.1) for the docetaxel group (hazard ratio = 0.76, 95% CI: 0.63–0.92, p = 0.0042). The objective response rate was 29.9% (95% CI: 24.0–36.2) for the nab-paclitaxel group and 15.4% (95% CI: 10.9–20.7) for the docetaxel group (p = 0.0002). Adverse events of grade greater than or equal to 3 included febrile neutropenia (5 of 245 patients [2%] in the nab-paclitaxel group versus 55 of 249 patients [22%] in the docetaxel group) and peripheral sensory neuropathy (24 [10%] versus 2 [1%], respectively). Conclusions Nab-paclitaxel was noninferior to docetaxel in terms of OS. It should, thus, be considered a standard treatment option for previously treated patients with advanced NSCLC.
- Published
- 2020
39. A randomized phase 3 study of maintenance therapy with S-1 plus best supportive care versus best supportive care after induction therapy with carboplatin plus S-1 for advanced or relapsed squamous cell carcinoma of the lung (WJOG7512L)
- Author
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Yoichi Nakanishi, Satoshi Morita, Haruko Daga, Ryo Toyozawa, Takuma Yokoyama, Yasuo Iwamoto, Kazuhiko Nakagawa, Satoru Miura, Kaoru Tanaka, Hiroshige Yoshioka, Katsuya Hirano, Tetsuya Oguri, Atsushi Nakamura, Masahiko Ando, Motoko Tachihara, Ryo Ko, Akihiro Bessho, Isamu Okamoto, Nobuyuki Yamamoto, and Takashi Ishiguro
- Subjects
Oncology ,Adult ,Male ,Cancer Research ,medicine.medical_specialty ,Lung Neoplasms ,Anemia ,viruses ,non-small cell lung cancer (NSCLC) ,Phases of clinical research ,Pemetrexed ,Carboplatin ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Maintenance therapy ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Humans ,030212 general & internal medicine ,Lung ,Aged ,Proportional Hazards Models ,Tegafur ,Squamous-cell carcinoma of the lung ,urogenital system ,business.industry ,Hazard ratio ,Area under the curve ,Induction Chemotherapy ,biochemical phenomena, metabolism, and nutrition ,Middle Aged ,medicine.disease ,Progression-Free Survival ,Drug Combinations ,Oxonic Acid ,Treatment Outcome ,chemistry ,030220 oncology & carcinogenesis ,Carcinoma, Squamous Cell ,Cisplatin ,business - Abstract
Background A randomized phase 3 study was performed to investigate the efficacy and safety of maintenance therapy with S-1 after induction therapy with carboplatin plus S-1 in patients with advanced squamous non-small cell lung cancer (NSCLC). Methods Chemotherapy-naive patients with advanced or relapsed squamous NSCLC were treated with carboplatin (area under the curve of 5 on day 1 every 3 weeks) plus S-1 (40 mg/m2 twice per day on days 1-14 every 3 weeks) as induction therapy. Patients who did not progress after 4 cycles of induction therapy were randomized to receive either S-1 plus best supportive care (BSC) or BSC alone. The primary objective of the study was to confirm the superiority of S-1 plus BSC in comparison with BSC alone with respect to progression-free survival. Results Of the 365 patients enrolled in the study, 347 participated in the induction phase, and 131 of these individuals were randomized to receive S-1 plus BSC (n = 67) or BSC alone (n = 64). The risk of disease progression was significantly lower for patients in the S-1 plus BSC arm than those in the BSC-alone arm (hazard ratio, 0.548; 95% confidence interval, 0.374-0.802; P = .0019). The most common toxicities during maintenance therapy with S-1 included anorexia, anemia, and fatigue, but most cases were not severe. Conclusions Continued maintenance with S-1 plus BSC is an effective and well-tolerated treatment option for patients with advanced squamous NSCLC previously treated with carboplatin plus S-1.
- Published
- 2020
40. ROCESS ANALYSIS OF IMPLEMENTATION OF TSUNAMI COUNTERMEASURES AFTER THE 1933 SHOWA SANRIKU TSUNAMI
- Author
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Chise NISHIWAKI, Makoto OKUMURA, and Katsuya HIRANO
- Published
- 2022
41. Therapeutic effect of lactulose on intestinal flora structure and composition in colitis-associated tumorigenesis
- Author
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Lin Kurahara, Feiyan Zhao, Keizo Hiraishi, Xiaodong Li, Heping Zhang, and Katsuya Hirano
- Subjects
Applied Mathematics ,General Mathematics - Published
- 2022
42. Characteristics of the adipocytes differentiated by a glucocorticoid receptor antagonist RU486
- Author
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Katsuya Hirano and Takeshi Hashimoto
- Subjects
Applied Mathematics ,General Mathematics - Published
- 2022
43. Vanishing natives and Taiwan’s settler-colonial unconsciousness
- Author
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Toulouse-Antonin Roy, Lorenzo Veracini, and Katsuya Hirano
- Subjects
History ,Sociology and Political Science ,Settler colonial ,0602 languages and literature ,05 social sciences ,Geography, Planning and Development ,0507 social and economic geography ,Lens (geology) ,06 humanities and the arts ,Ancient history ,060202 literary studies ,Colonialism ,050701 cultural studies - Abstract
What are the implications of recovering settler colonialism as a mode of domination that fundamentally shaped Taiwan’s history? The article argues that this uncovering is crucial to understanding the formation of successive polities on the island of Taiwan, but this is not to say that a settler-colonial studies lens should replace a colonial one.
- Published
- 2018
44. Endogenous Hydrogen Sulfide Contributes to Tone Generation in Porcine Lower Esophageal Sphincter Via Na+/Ca2+ Exchanger
- Author
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Haruei Ogino, Yoshimasa Tanaka, Eikichi Ihara, Mayumi Hirano, Kayoko Nakano, Yoshihiro Ogawa, Takahiro Iwamoto, Satomi Kita, Xiaopeng Bai, Katsuya Hirano, Kazuhiko Nakamura, and Yoshinao Oda
- Subjects
0301 basic medicine ,Sulfurtransferase ,Endogeny ,Contractility ,03 medical and health sciences ,Basal (phylogenetics) ,0302 clinical medicine ,otorhinolaryngologic diseases ,Extracellular ,Lower Esophageal Sphincter ,lcsh:RC799-869 ,Antrum ,chemistry.chemical_classification ,Hepatology ,Gastroenterology ,Anatomy ,Molecular biology ,Myogenic Tone Regulation ,Cytosol ,030104 developmental biology ,Enzyme ,Hydrogen Sulfate ,chemistry ,lcsh:Diseases of the digestive system. Gastroenterology ,030217 neurology & neurosurgery ,Na+/Ca2+ Exchanger - Abstract
Background and Aims Hydrogen sulfide (H2S) is a major physiologic gastrotransmitter. Its role in the regulation of the lower esophageal sphincter (LES) function remains unknown. The present study addresses this question. Methods Isometric contraction was monitored in circular smooth muscle strips of porcine LES. Changes in cytosolic Ca2+ concentration ([Ca2+]i) and force were simultaneously monitored in fura-2-loaded strips with front-surface fluorometry. The contribution of endogenous H2S to LES contractility was investigated by examining the effects of inhibitors of H2S-generating enzymes, including cystathionine-β-synthase, cystathionine-γ-lyase, and 3-mercaptopyruvate sulfurtransferase, on the LES function. Results Porcine LES strips myogenically maintained a tetrodotoxin-resistant basal tone. Application of AOA (cystathionine-β-synthase inhibitor) or L-aspartic acid (L-Asp; 3-mercaptopyruvate sulfurtransferase inhibitor) but not DL-PAG (cystathionine-γ-lyase inhibitor), decreased this basal tone. The relaxant effects of AOA and L-Asp were additive. Maximum relaxation was obtained by combination of 1 mM AOA and 3 mM L-Asp. Immunohistochemical analyses revealed that cystathionine-β-synthase and 3-mercaptopyruvate sulfurtransferase, but not cystathionine-γ-lyase, were expressed in porcine LES. AOA+L-Asp–induced relaxation was accompanied by a decrease in [Ca2+]i and inversely correlated with the extracellular Na+ concentration ([Na+]o) (25-137.4 mM), indicating involvement of an Na+/Ca2+ exchanger. The reduction in the basal [Ca2+]i level by AOA was significantly augmented in the antral smooth muscle sheets of Na+/Ca2+ exchanger transgenic mice compared with wild-type mice. Conclusions Endogenous H2S regulates the LES myogenic tone by maintaining the basal [Ca2+]i via Na+/Ca2+ exchanger. H2S-generating enzymes may be a potential therapeutic target for esophageal motility disorders, such as achalasia.
- Published
- 2018
45. A FACILITATION AND INHIBITION IN RECOGNITION OF JAPANESE HISTORICAL STREETSCAPE BASED ON CUED RECALL TASK
- Author
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Katsuya Hirano, Hirotoshi Shirayanagi, and Yasuaki Kawata
- Subjects
Cued recall ,Facilitation ,Psychology ,Task (project management) ,Cognitive psychology - Published
- 2018
46. OA03.05 Phase III Study Comparing Nab-Paclitaxel With Docetaxel in Patients With Previously Treated Advanced Non-Small-Cell Lung Cancer
- Author
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Satoshi Morita, Takafumi Kubo, Tetsuya Oguri, Terufumi Kato, Masashi Kondo, Y. Nakanishi, Yasuto Yoneshima, Toshiyuki Harada, Masafumi Takeshita, Katsuya Hirano, Hiroshige Yoshioka, Yukio Hosomi, Junji Kishimoto, Nobuyuki Yamamoto, M. Ando, Shunichiro Iwasawa, Yasuhiro Goto, Isamu Okamoto, Satoru Miura, and Atsushi Nakamura
- Subjects
Pulmonary and Respiratory Medicine ,business.industry ,medicine.disease ,Oncology ,Docetaxel ,Cancer research ,Medicine ,In patient ,Non small cell ,business ,Previously treated ,Lung cancer ,medicine.drug ,Nab-paclitaxel - Published
- 2021
47. FP14.16 Phase 2 Trial of the Alternating Therapy with Osimertinib and Afatinib for Treatment-Naive Patients with EGFR-Mutated Advanced Non–Small Cell Lung Cancer (WJOG10818L/Alt Trial)
- Author
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Kimio Yonesaka, Motoko Tachihara, Shinya Sakata, Osamu Hataji, K. Sakai, Yasutaka Chiba, Shunichi Sugawara, Satoshi Ikeda, Nobuyuki Yamamoto, Kazuhiko Nakagawa, Yuki Sato, Y. Yano, Hidetoshi Hayashi, Kazuto Nishio, H. Okada, Toshihide Yokoyama, Haruko Daga, Katsuya Hirano, and Koichi Azuma
- Subjects
Pulmonary and Respiratory Medicine ,Oncology ,medicine.medical_specialty ,business.industry ,Afatinib ,medicine.disease ,Therapy naive ,Internal medicine ,medicine ,Osimertinib ,Non small cell ,Lung cancer ,business ,medicine.drug - Published
- 2021
48. MO29-5 RELAY+: Exploratory study of RAM+GEF in untreated patients with EGFR M+ NSCLC: Updates on efficacy, safety and biomarker
- Author
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Tomoko Matsui, Hiroyuki Yamaguchi, Martin Reck, Satoshi Ikeda, Makoto Nishio, Carla Visseren-Grul, Kazuhiko Nakagawa, Edward B. Garon, Sotaro Enatsu, Sameera R. Wijayawardana, Annamaria Zimmermann, Katsuya Hirano, Kazuto Nishio, Fumio Imamura, Tomoya Kawaguchi, Matteo Ceccarelli, and Gosuke Homma
- Subjects
Oncology ,medicine.medical_specialty ,business.industry ,Internal medicine ,Exploratory research ,Medicine ,Biomarker (medicine) ,Hematology ,business - Published
- 2021
49. Efficacy of olanzapine combined with the standard triplet antiemetic therapy for cisplatin-based chemotherapy: A sub-analysis of a randomized, double-blind, placebo-controlled trial (J-FORCE)
- Author
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Yukio Sakata, Toshiaki Nakayama, Masakazu Abe, Kensuke Hori, Hiroki Ueda, Takuhiro Yamaguchi, Jun Okamura, Yukiyoshi Fujita, Takeshi Aoyama, Koichi Kitagawa, Sadamoto Zenda, Haruko Daga, Yasuhiko Sakata, Hirotoshi Iihara, Katsuya Hirano, Yasuhiro Shimada, Kazuhiko Shibata, and Hironobu Hashimoto
- Subjects
Olanzapine ,Cisplatin ,Oncology ,Cancer Research ,medicine.medical_specialty ,business.industry ,medicine.drug_class ,Placebo-controlled study ,Double blind ,Cisplatin based chemotherapy ,Internal medicine ,medicine ,Antiemetic ,business ,medicine.drug - Abstract
12098 Background: In a randomized, double-blind, placebo-controlled trial (J-FORCE), we previously reported the efficacy of olanzapine (OLZ) 5 mg plus triplet antiemetic therapy for cisplatin (CDDP)-based chemotherapy-induced nausea and vomiting (CINV) in the delayed phase (24–120 h after CDDP treatment). Here, we report the results of a pre-planned subgroup analysis of this trial (in which risk factors were used as the allocation factors). This analysis was designed to determine which patients benefit more from OLZ. Methods: Subgroup analysis was performed on complete response (CR: no emesis and no rescue medication) in the acute (within 24 h of CDDP treatment) and delayed phase and time to treatment failure (TTF: time from CDDP treatment to the first vomiting or use of rescue medication). Data from 705 patients in the efficacy analysis population (354 in the OLZ group and 351 in the placebo (PLA) group) were analyzed by sex (male/female), age (≥55 years/ < 55 years), and CDDP dose (≥70 mg/m2/ < 70 mg/m2). For CR, we calculated point estimates of differences between groups and 95% confidence intervals and performed a Mantel-Haenszel test. We used the Kaplan-Meier method for the analysis of TTF, and comparisons between groups were made using a log-rank test. Results: Delayed CR (OLZ versus PLA) and risk difference (RD) of delayed CR following OLZ treatment were significantly greater than following PLA in the following subgroups: male (83.1% versus 70.5%, RD 12.6%, p = 0.001), female (70.9% versus 56.4%, RD 14.5%, p = 0.021), age ≥55 years (78.7% versus 67.6%, RD 11.1%, p = 0.003), age < 55 years (81.0% versus 57.4%, RD 23.6%, p = 0.005), and CDDP ≥70 mg/m2 (78.8% versus 65.3%, RD 13.5%, p < 0.001). TTF of all subgroups (male/female, ≥55 years/ < 55 years, and ≥70 mg/m2/ < 70 mg/m2) was significantly longer in the OLZ group than in the PLA group (HR 0.493, p < 0.001; HR 0.612, p = 0.022; HR 0.586, p < 0.001; HR 0.401, p = 0.005; HR 0.546, p < 0.001; HR 0.543, p = 0.031, respectively). Conclusions: Our results suggest a benefit of OLZ 5 mg plus triplet therapy regardless of risk factors for CDDP-based CINV. Clinical trial information: UMIN000024676. [Table: see text]
- Published
- 2021
50. Protein phosphatases 1 and 2A and their naturally occurring inhibitors: current topics in smooth muscle physiology and chemical biology
- Author
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Masumi Eto, Masaru Watanabe, Akira Takai, Katsuya Hirano, Toshiyuki Wakimoto, and Kosuke Takeya
- Subjects
0301 basic medicine ,Cell physiology ,Physiology ,Phosphatase ,Chemical biology ,Review ,macromolecular substances ,Protein tyrosine phosphatase ,Signal transduction ,Biology ,environment and public health ,03 medical and health sciences ,Protein phosphorylation ,Smooth muscle ,Protein phosphatase 1 ,Phosphatase inhibitors ,Protein phosphatase 2A ,Protein phosphatase 2 ,Cell biology ,enzymes and coenzymes (carbohydrates) ,030104 developmental biology ,Biochemistry ,embryonic structures - Abstract
Protein phosphatases 1 and 2A (PP1 and PP2A) are the most ubiquitous and abundant serine/threonine phosphatases in eukaryotic cells. They play fundamental roles in the regulation of various cellular functions. This review focuses on recent advances in the functional studies of these enzymes in the field of smooth muscle physiology. Many naturally occurring protein phosphatase inhibitors with different relative PP1/PP2A affinities have been discovered and are widely used as powerful research tools. Current topics in the chemical biology of PP1/PP2A inhibitors are introduced and discussed, highlighting the identification of the gene cluster responsible for the biosynthesis of calyculin A in a symbiont microorganism of a marine sponge.
- Published
- 2017
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