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Masanobu Tsubaki,Tomoya Takeda,Takuya Matsuda,Akihiro Kimura,Remi Tanaka,Sakiko Nagayoshi,Tadafumi Hoshida,Kazufumi Tanabe,Shozo Nishida 생화학분자생물학회 2023 BMB Reports Vol.56 No.2
Chronic myeloid leukemia (CML) has a markedly improvedprognosis with the use of breakpoint cluster region-abelson 1(BCR-ABL1) tyrosine kinase inhibitors (BCR-ABL1 TKIs). However,approximately 40% of patients are resistant or intolerantto BCR-ABL1 TKIs. Hypoxia-inducible factor 1α (HIF-1α) is ahypoxia response factor that has been reported to be highlyexpressed in CML patients, making it a therapeutic target forBCR-ABL1 TKI-sensitive CML and BCR-ABL1 TKI-resistant CML. In this study, we examined whether HIF-1α inhibitors inducecell death in CML cells and BCR-ABL1 TKI-resistant CML cells. We found that echinomycin and PX-478 induced cell death inBCR-ABL1 TKIs sensitive and resistant CML cells at similar concentrationswhile the cell sensitivity was not affected with imatinibor dasatinib in BCR-ABL1 TKIs resistant CML cells. In addition,echinomycin and PX-478 inhibited the c-Jun N-terminalkinase (JNK), Akt, and extracellular-regulated protein kinase 1/2(ERK1/2) activation via suppression of BCR-ABL1 and Met expressionin BCR-ABL1 sensitive and resistant CML cells. Moreover,treatment with HIF-1α siRNA induced cell death by inhibitingBCR-ABL1 and Met expression and activation of JNK,Akt, and ERK1/2 in BCR-ABL1 TKIs sensitive and resistant CMLcells. These results indicated that HIF-1α regulates BCR-ABL andMet expression and is involved in cell survival in CML cells,suggesting that HIF-1α inhibitors induce cell death in BCR-ABL1TKIs sensitive and resistant CML cells and therefore HIF-1α inhibitorsare potential candidates for CML treatment.
Atomic Force Microscopic Study of Chitinase Binding onto Chitin and Cellulose Surfaces
Kikkawa, Yoshihiro,Fukuda, Masato,Kimura, Tomoya,Kashiwada, Ayumi,Matsuda, Kiyomi,Kanesato, Masatoshi,Wada, Masahisa,Imanaka, Tadayuki,Tanaka, Takeshi American Chemical Society 2014 Biomacromolecules Vol.15 No.3
<P><B>Graphic Abstract</B> <IMG SRC='http://pubs.acs.org/appl/literatum/publisher/achs/journals/content/bomaf6/2014/bomaf6.2014.15.issue-3/bm500046f/production/images/medium/bm-2014-00046f_0004.gif'></P><P><A href='http://pubs.acs.org/doi/suppl/10.1021/bm500046f'>ACS Electronic Supporting Info</A></P>
Rimmed Vacuoles in Myositis Associated with Antimitochondrial Antibody
Rui Shimazaki,Akinori Uruha,Hideki Kimura,Utako Nagaoka,Tomoya Kawazoe,Satoshi Yamashita,Takashi Komori,Kazuhito Miyamoto,Shiro Matsubara,Keizo Sugaya,Masahiro Nagao,Eiji Isozaki 대한신경과학회 2020 Journal of Clinical Neurology Vol.16 No.3
Yuji Hotta,Naoya Ieda,Ayako Fukamoto,Tomoya Kataoka,Yoshihiro Kawade,Yasuhiro Maeda,Hidehiko Nakagawa,Kazunori Kimura 대한비뇨의학회 2016 Investigative and Clinical Urology Vol.57 No.3
Purpose: To investigate whether relaxation of the rat penile corpus cavernosum could be controlled with NOBL-1, a novel, light-controllable nitric oxide (NO) releaser. Materials and Methods: Fifteen-week-old male Wistar-ST rats were used. The penile corpus cavernosum was prepared and used in an isometric tension study. After noradrenaline (10-5 M) achieved precontraction, the penile corpus cavernosum was irradiated by light (470–500 nm) with and without NOBL-1 (10-6 M). In addition, we noted rats' responses to light with vardenafil (10-6 M), a phosphodiesterase-5 (PDE-5) inhibitor. Next, responses to light in the presence of a guanylate cyclase inhibitor, ODQ (1H-[1,2,4] oxadiazolo[4,3-a]quinoxalin-1-one) (10-5 M), were measured. All measurements were performed in pretreated L-NAME (10-4 M) conditions to inhibit endogenous NO production. Results: Corpus cavernosal smooth muscle, precontracted with noradrenaline, was unchanged by light irradiation in the absence of NOBL-1. However, in the presence of NOBL-1, corpus cavernosal smooth muscle, precontracted with noradrenaline, relaxed in response to light irradiation. After blue light irradiation ceased, tension returned. In addition, the light response was obviously enhanced in the presence of a PDE-5 inhibitor. Conclusions: This study showed that rat corpus cavernosal smooth muscle relaxation can be light-controlled using NOBL-1, a novel, light sensitive NO releaser. Though further in vivo studies are needed to investigate possible usefulness, NOBL-1 may be prove to be a useful tool for erectile dysfunction therapy, specifically in the field of penile rehabilitation.
( Rintaro Moroi ),( Katsuya Endo ),( Katsutoshi Yamamoto ),( Takeo Naito ),( Motoyuki Onodera ),( Masatake Kuroha ),( Yoshitake Kanazawa ),( Tomoya Kimura ),( Yoichi Kakuta ),( Atsushi Masamune ),( Yo 대한장연구학회 2019 Intestinal Research Vol.17 No.1
Background/Aims: Few reports have described the long-term treatment outcomes of the anti-tumor necrosis factor-α antibody for Japanese Crohn’s disease (CD) patients. The aim of this study was to evaluate them and clarify the clinical factors that affect the long-term prognosis of the anti-tumor necrosis factor-α treatments. Methods: This was a retrospective, observational, single-center cohort study. Japanese CD patients treated with either infliximab or adalimumab as a first-line therapy were analyzed. The cumulative retention rates of the biologics, relapse-free survival, and surgery-free survival were analyzed using Kaplan-Meier methods. The clinical factors associated with the long-term outcomes were estimated by both the log-rank test and Cox proportional hazard model. Results: The cumulative retention rate was significantly higher in the group with a concomitant elemental diet of ≥900 kcal/day, baseline C-reactive protein (CRP) levels <2.6 mg/dL, and baseline serum albumin levels ≥3.5 g/dL, respectively. The baseline serum albumin levels were also associated with both relapse-free and surgery-free survival. The lack of concomitant use of an elemental diet ≥900 kcal/day was identified as the only independent risk factor for the withdrawal of the biologics. Conclusions: Baseline CRP levels and serum albumin levels could affect the long-term outcomes in CD patients. Concomitant elemental diet of ≥900 kcal/day could have a positive influence on clinical treatment course. (Intest Res 2019;17:94-106)