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81.
Yasunobu Matsuda Ayumi Sanpei Toshifumi Wakai Masayuki Kubota Mami Osawa Yuki Hirose Jun Sakata Takashi Kobayashi Shun Fujimaki Masaaki Takamura Satoshi Yamagiwa Masahiko Yano Shogo Ohkoshi Yutaka Aoyagi 《International journal of clinical and experimental pathology》2014,7(5):2032-2043
Hepatitis B virus X (HBX) protein plays a crucial role in carcinogenesis, but its mechanism is unclear. The involvement of ataxia telangiectasia mutated (ATM) kinase in the enhanced redox system was investigated by examining the phosphorylation level of ATM in HBX gene-transfected cells and in transgenic mice following redox system manipulation by treatment with hydrogen peroxide (H2O2) or antioxidant. Western blotting and immunostaining showed that phospho-ATM was significantly increased by HBX both in vitro (3.2-fold; p<0.05) and in vivo (4-fold; p<0.05), and this effect was abrogated by antioxidant treatment. The level of PKC-δ in HBX-expressing cells was increased 3.5-fold compared to controls. Nuclear localized NF-E2-related factor 2 (Nrf2) was increased in HBX-expressing cells exposed to H2O2, but remained at lower levels after the treatment with rottlerin, KU55933, or caffeine. The levels of anti-oxidant molecules were increased in HBX expressing cells and in transgenic mice, indicating that HBX stimulates the Nrf2-mediated redox system. The levels of intracellular reactive oxygen species (ROS) were significantly increased in HBX-expressing cells treated with hydrogen peroxide in the presence of ATM inhibitor KU55933 or caffeine. Treatment of HBX-expressing cells with KU55933 or caffeine before the exposure to H2O2 increased the ratio of cell apoptosis to 33 ± 4% (p<0.05) and 22 ± 4% (p<0.05), respectively. Collectively, HBX stimulates the ATM-mediated PKC-δ/Nrf2 pathway, and maintains the enhanced activity of the redox system. Therefore, manipulating ATM kinase activity might be a useful strategy for treating HBX-induced carcinogenesis. 相似文献
82.
Mutsumi Wakabayashi Yasunobu Sekiguchi Asami Shimada Kunimoto Ichikawa Keiji Sugimoto Shigeki Tomita Hiroshi Izumi Noriko Nakamura Tomohiro Sawada Yasunori Ohta Norio Komatsu Masaaki Noguchi 《International journal of clinical and experimental pathology》2014,7(11):8190-8197
A 60-year-old man complained of nausea, vomiting, decreased appetite, and a feeling of abdominal fullness in August 2013. Based on biopsy findings from an upper gastrointestinal endoscopy examination, a diagnosis of non-Hodgkin’s lymphoma (NHL), diffuse large B-cell lymphoma (DLBCL), non-GC type, was made. F18-fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) revealed abnormal accumulations solely in the gastric wall (SUVmax = 14.5), the left adrenal gland (SUVmax = 14.3), and the right adrenal gland (SUVmax = 8.5). The clinical stage (Ann Arbor) was IVA, the serum LDH level was within the reference range, and the International Prognostic Index (IPI) was low-intermediate. The serum soluble IL-2 receptor level was within the reference range, and there was no evidence of HIV, EB virus, or autoimmune disease. After the completion of 4 cycles of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) and 2 parallel cycles of prophylactic intrathecal (I.T.), an upper gastrointestinal endoscopy and a FDG-PET/CT examination showed complete remission (CR). The patient received 8 cycles of ritsuximab therapy, 6 cycles of CHOP, and 3 cycles of I.T. The patient has maintained a CR for about 14 months. A literature search revealed that malignant lymphoma with involvement confined to the adrenal gland and gastrointestinal tract is exceedingly rare, and only 3 cases of malignant lymphoma have been reported, with involvement of the stomach in 2 cases and the duodenum in 1 case. All of the cases were diagnosed as DLBCL. The case described herein represents the third case with involvement of the stomach. 相似文献
83.
Masaharu Murase Yasuhiro Kodera Ken Kondo Hiroyuki Sekiguchi Michitaka Fujiwara Yasushi Kasai Seiji Akiyama Katsuki Ito Hiroshi Takagi 《Journal of surgical oncology》1996,61(3):223-229
The mRNA expression of mdr1 and MRP, each of which codes for a transport protein belonging to ATP-binding cassette superfamily and are reported to be responsible for multidrug resistance phenotype, were semiquantified by RT-PCR in a panel of gastrointestinal cancer cell lines. Although the expression of MRP was predominant in esophageal cancer cell lines, expression of either or both of the genes was detected in all the cell lines tested. Expression of these two genes added together correlated significantly with chemosensitivity against doxorubicin, implicating that expression of both genes should be evaluated in the future analysis of multidrug resistance phenotype. The ID50 values for pirarubicin, although generally lower than the values for doxorubicin, correlated well with the latter, suggesting that the similar phenotype as that for doxorubicin might be responsible for drug resistance against this semisynthetic anthracycline glycoside. © 1996 Wiley-Liss, Inc. 相似文献
84.
Hiroaki Yamamoto Toyozo Sekiguchi Keiko Itagaki Shinobu Saijo Yoichiro Iwakura 《Arthritis \u0026amp; Rheumatology》1993,36(11):1612-1620
Objective. We have recently reported that arthropathy develops in high incidence among transgenic mice carrying the pX region of human T cell leukemia virus type I (HTLV-I). In the present study, the histopathologic features of the joints in these mice were examined in order to compare the animal disease with rheumatoid arthritis (RA) in humans. Methods. Paraffin sections of limbs (right and left fingers, wrists, elbows, shoulders, toes, knees, and ankles) were stained with hematoxylin and eosin, periodic acid–Schiff, azan-Mallory, or phosphotungstic acid hematoxylin, and examined by light microscopy. Results. Abnormalities of the limbs began to occur as early as 3 weeks of age, and the incidence gradually increased until the mice were 12 months old. The incidence of arthropathy was 22% (48 of 217) at 3 months of age and 28% (18 of 64) at 6 months. The severity of the histopathologic changes in the joints of the transgenic mice ranged from grade I to grade IV. Conclusion. The major histopathologic features in the joints of HTLV-I transgenic mice are similar to those in humans with RA. Thus, these mice may represent a useful model for the study of the disease in humans. 相似文献
85.
Masahiro Itonaga Masayuki Kitano Takanori Yoshikawa Reiko Ashida Yasunobu Yamashita Kenichi Hatamaru Mamoru Takenaka Tomohiro Yamazaki Takeshi Ogura Nobu Nishioka Arata Sakai Atsuhiro Masuda Hideyuki Shiomi Toshio Shimokawa 《Medicine》2021,100(12)
Introduction:In patients with malignant distal bile duct obstruction and normal gastrointestinal anatomy, endoscopic ultrasound-guided choledochoduodenostomy (EUS-CDS) is indicated when endoscopic retrograde cholangiopancreatography (ERCP) fails. The ERCP drainage route passes through the tumor, whereas the EUS-CDS route does not. Therefore, EUS-CDS is expected to have a longer stent patency than ERCP. However, for first-line biliary drainage, it remains unclear whether EUS-CDS or ERCP is superior in terms of stent patency. To reduce the frequency of highly adverse events (AEs) such as bile peritonitis or stent migration following EUS-CDS, we developed an antimigration metal stent with a thin delivery system for tract dilatation. This study is designed to assess whether EUS-CDS with this novel stent is superior to ERCP with a traditional metal stent in terms of stent patency when the two techniques are used for first-line drainage of malignant distal biliary obstruction.Methods/design:This study is a multicenter single-blinded randomized controlled trial (RCT) involving 95 patients in four tertiary centers. Patients with malignant distal biliary obstruction that is unresectable or presents a very high surgical risk and who pass the inclusion and exclusion criteria will be randomized to EUS-CDS or ERCP in a 1:1 proportion. The primary endpoint is the stent patency rate 180 days after stent insertion. Secondary outcomes include the rates of technical success, clinical success, technical success in cases not requiring fistulous-tract dilation (only EUS-CDS group), procedure-related AEs, re-intervention success, patients receiving post-drainage chemotherapy, procedure time, and overall survival time.Discussion:If EUS-CDS is superior to ERCP in terms of stent patency and safety for the first-line drainage of malignant distal biliary obstruction, it is expected that the first-line drainage method will be changed from ERCP to EUS-CDS, and that interruption of chemotherapy due to stent dysfunction can be avoided.Trial registration:University Hospital Medical Information Network Clinical Trials Registry (UMIN-CTR), ID: UMIN000041343. Registered on August 6, 2020. https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000047201Version number: 1.2, December 7, 2020. 相似文献
86.
Masahito Sawahata Daisuke Mori Yuko Arioka Hisako Kubo Itaru Kushima Kanako Kitagawa Akira Sobue Emiko Shishido Mariko Sekiguchi Akiko Kodama Ryosuke Ikeda Branko Aleksic Hiroki Kimura Kanako Ishizuka Taku Nagai Kozo Kaibuchi Toshitaka Nabeshima Kiyofumi Yamada Norio Ozaki 《Psychiatry and clinical neurosciences》2020,74(5):318-327
87.
Naohiro Sekiguchi Shinya Rai Wataru Munakata Kenshi Suzuki Hiroshi Handa Hirohiko Shibayama Tomoyuki Endo Yasuhito Terui Noriko Iwaki Noriko Fukuhara Hiro Tatetsu Shinsuke Iida Takayuki Ishikawa Ryota Shiibashi Koji Izutsu 《Cancer science》2020,111(9):3327-3337
Tirabrutinib is a second‐generation Bruton’s tyrosine kinase inhibitor with greater selectivity than ibrutinib. Here, we conducted a multicenter, phase II study of tirabrutinib in patients with treatment‐naïve (Cohort A) or with relapsed/refractory (Cohort B) Waldenström’s macroglobulinemia (WM). Patients were treated with tirabrutinib 480 mg once daily. The primary endpoint was major response rate (MRR; ≥ partial response). Secondary endpoints included overall response rate (ORR; ≥ minor response), time to major response (TTMR), progression‐free survival (PFS), overall survival (OS), and safety. In total, 27 patients (18 in Cohort A; 9 in Cohort B) were enrolled. The median age was 71 y, and the median serum immunoglobulin M level was 3600 mg/dL. Among the patients, 96.2% had the MYD88L265P mutation. MRR and ORR were 88.9% and 96.3%, respectively (Cohort A: MRR, 88.9%; ORR, 94.4%; Cohort B: MRR, 88.9%; ORR, 100%). Median TTMR was 1.87 mo. PFS and OS were not reached with a median follow‐up of 6.5 and 8.3 mo for Cohorts A and B, respectively. The most common adverse events (AEs) were rash (44.4%), neutropenia (25.9%), and leukopenia (22.2%), with most AEs classified as grade 1 or 2. Grade ≥ 3 AEs included neutropenia (11.1%), lymphopenia (11.1%), and leukopenia (7.4%). No grade 5 AEs were noted. All bleeding events were grade 1; none were associated with drug‐related atrial fibrillation or hypertension. Although the follow‐up duration was relatively short, the study met the primary endpoint. Therefore, tirabrutinib monotherapy is considered to be highly effective for both untreated and relapsed/refractory WM with a manageable safety profile. (JapicCTI‐173646). 相似文献
88.
Harumi Hotta Kazuto Masamoto Sae Uchida Yuta Sekiguchi Hiroyuki Takuwa Hiroshi Kawaguchi Kazuhiro Shigemoto Ryo Sudo Kazuo Tanishita Hiroshi Ito Iwao Kanno 《Journal of cerebral blood flow and metabolism》2013,33(9):1440-1447
To clarify mechanisms through which activation of the nucleus basalis of Meynert (NBM) increases cerebral cortical blood flow, we examined whether cortical parenchymal arteries dilate during NBM stimulation in anesthetized mice. We used two-photon microscopy to measure the diameter of single penetrating arteries at different depths (∼800 μm, layers I to V) of the frontal cortex, and examined changes in the diameter during focal electrical stimulation of the NBM (0.5 ms at 30 to 50 μA and 50 Hz) and hypercapnia (3% CO2 inhalation). Stimulation of the NBM caused diameter of penetrating arteries to increase by 9% to 13% of the prestimulus diameter throughout the different layers of the cortex, except at the cortical surface and upper part of layer V, where the diameter of penetrating arteries increased only slightly during NBM stimulation. Hypercapnia caused obvious dilation of the penetrating arteries in all cortical layers, including the surface arteries. The diameters began to increase within 1 second after the onset of NBM stimulation in the upper cortical layers, and later in lower layers. Our results indicate that activation of the NBM dilates cortical penetrating arteries in a layer-specific manner in magnitude and latency, presumably related to the density of cholinergic nerve terminals from the NBM. 相似文献
89.
90.
Ogawa T Kim GH Sekiguchi H Akai M Suzuki S Nakazawa K 《European journal of applied physiology》2009,105(2):199-205
The purpose of this study was to investigate effects of long-term participation to swimming on adaptations of spinal reflex
excitability. To this end, mechanically induced stretch reflex (SR) and electrically induced Hoffmann (H-) reflex of the soleus
muscle were investigated between swimmers with experience of more than 10 years and non-trained individuals while sitting
at rest. The amplitude and the gain (stretch velocity vs. amplitude of the reflex response) of the SR were significantly greater
in the swimming group than in the non-trained control group. Similarly, the responses of the H-reflex were also significantly
greater in the swimming group than in the non-trained control group. Results of this study demonstrated that the spinal reflex
excitability in experienced swimmers was far more enhanced than in non-trained individuals. 相似文献