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( Takamasa Ishii ),( Masaki Miyazawa ),( Phil S. Hartman ),( Naoaki Ishii ) 생화학분자생물학회(구 한국생화학분자생물학회) 2011 BMB Reports Vol.44 No.5
Most intracellular reactive oxygen species (ROS), especially superoxide anion (O2·-) that is converted from oxygen, are overproduced by excessive electron leakage from the mitochondrial respiratory chain. Intracellular oxidative stress that damages cellular components can contribute to lifestyle-related diseases such as diabetes and arteriosclerosis, and age-related diseases such as cancer and neuronal degenerative diseases. We have previously demonstrated that the excessive mitochondrial O2·- production caused by SDHC mutations (G71E in C. elegans, I71E in Drosophila and V69E in mouse) results in premature death in C. elegans and Drosophila, cancer in mouse embryonic fibroblast cells and infertility in transgenic mice. SDHC is a subunit of mitochondrial complex II. In humans, it has been reported that mutations in SDHB, SDHC or SDHD often result in inherited head and neck paragangliomas (PGLs). Recently, we established Tet-mev-1 conditional transgenic mice using our uniquely developed Tet-On/Off system, which equilibrates transgene expression to endogenous levels. These mice experienced mitochondrial respiratory chain dysfunction that resulted in O2·- overproduction. The mitochondrial oxidative stress caused excessive apoptosis leading to low birth weight and growth retardation in the neonatal developmental phase in Tet-mev-1 mice. Here, we briefly describe the relationships between mitochondrial O2·- and aging phenomena in mev-1 animal models. [BMB reports 2011; 44(5): 298-305]
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Tomoyuki Hayashi,Yoshiro Asahina,Yasuhito Takeda,Masaki Miyazawa,Hajime Takatori,Hidenori Kido,Jun Seishima,Noriho Iida,Kazuya Kitamura,Takeshi Terashima,Sakae Miyagi,Tadashi Toyama,Eishiro Mizukoshi 대한소화기내시경학회 2023 Clinical Endoscopy Vol.56 No.5
Background/Aims: The necessity for pharyngeal anesthesia during upper gastrointestinal endoscopy is controversial. This study aimedto compare the observation ability with and without pharyngeal anesthesia under midazolam sedation. Methods: This prospective, single-blinded, randomized study included 500 patients who underwent transoral upper gastrointestinalendoscopy under intravenous midazolam sedation. Patients were randomly allocated to pharyngeal anesthesia: PA+ or PA– groups (250patients/group). The endoscopists obtained 10 images of the oropharynx and hypopharynx. The primary outcome was the non-inferiorityof the PA- group in terms of the pharyngeal observation success rate. Results: The pharyngeal observation success rates in the pharyngeal anesthesia with and without (PA+ and PA–) groups were 84.0%and 72.0%, respectively. The PA– group was inferior (p=0.707, non-inferiority) to the PA+ group in terms of observable parts (8.33 vs. 8.86, p=0.006), time (67.2 vs. 58.2 seconds, p=0.001), and pain (1.21±2.37 vs. 0.68±1.78, p=0.004, 0–10 point visual analog scale). Suitablequality images of the posterior wall of the oropharynx, vocal fold, and pyriform sinus were inferior in the PA– group. Subgroupanalysis showed a higher sedation level (Ramsay score ≥5) with almost no differences in the pharyngeal observation success rate betweenthe groups. Conclusions: Non-pharyngeal anesthesia showed no non-inferiority in pharyngeal observation ability. Pharyngeal anesthesia may improvepharyngeal observation ability in the hypopharynx and reduce pain. However, deeper anesthesia may reduce this difference.
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The Impact of Neoadjuvant Chemotherapy for Borderline Resectable Pancreatic Cancer
( Manabu Kawai ),( Seiko Hirono ),( Ken-ichi Okada ),( Motoki Miyazawa ),( Yuji Kitahata ),( Ryohei Kobayashi ),( Masaki Ueno ),( Shinya Hayami ),( Hiroki Yamaue ) 대한간학회 2018 춘·추계 학술대회 (KASL) Vol.2018 No.1
Backgrounds: According to the National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines, pancre atic ductal adenocarcinoma (PDAC) can be classified as resectable, borderline resectable, or unresectable. Although borderline resectable PDAC (BRPC) may technically be resectable, it has particularly high risks of margin-positive resection and postoperative recurrence. Therefore, preoperative treatment is recommended for BRPC patients in both the NCCN Guidelines and an expert consensus statement. However, the establishment of the most appropriate neoadjuvant therapy is needed by further studies. The aim of these studies is to evaluate the impact of neoadjuvant chemotherapy for BRPC and confirm the safety and efficacy of two regimens of neoadjuvant therapy for BRPC. Our Clinical Trials: First, we evaluated the impact of neoadjuvant chemotherapy for BRPC. 143 BRPC-A patients un dergoing pancreatectomy were reviewed from among 330 pancreatic cancer patients, including 111 potentially resectable pancreatic cancer patients and 76 BRPC with portal vein involvement patients. We compared the clinico pathological factors of 40 BRPC-A patients treated with neoadjuvant treatment followed by surgery and those of 103 BRPC-A patients treated with upfront surgery. The R0 rate and progression-free survival of BRPC-A patients who received neoadjuvant therapy and subsequent surgical resection were significantly better compared to those who re ceived upfront surgery (R0: P = 0.041; progression-free survival: P = 0.033), but overall survival was not significantly different. Neoadjuvant treatment followed by surgery might provide clinical benefits for BRPC-A patients; however, the establishment of the most appropriate neoadjuvant treatment is needed by further studies. To evaluate appro priate neoadjuvant treatment, two prospective pilot trials were conducted as follows; modified FOLFIRINOX (without bolus 5-FU and LV, also decreased the dose of irinotecan; FIRINOX) and nab-paclitaxel plus gemcitabine therapy. Modified FOLFIRINOX was given to the first five patients in the 4-cycle group of the regimen and next five patients in the 8-cycle group. The primary end point was the toxicity of the therapy and one of the secondary end points were the optimal duration. The overall rate of grade 3 and 4 events was 80 %: 3 patients (60%) in the four-cycle group and five patients (100%) in the eight-cycle group had grade 3 or 4 adverse events. There was no incidence of seri ous adverse effect such as febrile neutropenia, sepsis, liver abscess or uncontrollable diarrhea. There was no clinically relevant morbidity presented in patients who underwent surgery. R0 rates by intention to treat were 60.0% in the four-cycle group and 40 % in the eight-cycle group (P = 0.999). The histopathologic treatment effect based on the Evans grade revealed grade I (n = 1), IIa (n = 3) in the four-cycle group and grade I (n = 2), IIa (n = 1) in the eight-cy cle group. Nab-paclitaxel plus gemcitabine therapy: the primary endpoint was the toxicity, and secondary endpoints were the resection rate, the R0 resection rate. The overall rate of any grade and grade 3-4 events were 100% and 90%. The majority of these adverse events represented expected neutropenia. The resection and R0 resection rates were 80% and 70%, respectively. Conclusion: FIRINOX therapy was feasible and safe for strictly selected patients with BRPC. On the other hand, nab-pa clitaxel plus gemcitabine therapy was safe and feasible without strict selection of patients with BRPC. A multicenter phase II study is in progress to investigate the efficacy of neoadjuvant nab-paclitaxel plus gemcitabine therapy on overall survival (UMIN000024154).
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