Cholesteryl Ester Transfer Protein (CETP) Deficiency and CETP Inhibitors

Mabuchi, Hiroshi,Nohara, Atsushi,Inazu, Akihiro Korean Society for Molecular and Cellular Biology 2014 Molecules and cells Vol.37 No.11

Epidemiologic studies have shown that low-density lipoprotein cholesterol (LDL-C) is a strong risk factor, whilst high-density lipoprotein cholesterol (HDL-C) reduces the risk of coronary heart disease (CHD). Therefore, strategies to manage dyslipidemia in an effort to prevent or treat CHD have primarily attempted at decreasing LDL-C and raising HDL-C levels. Cholesteryl ester transfer protein (CETP) mediates the exchange of cholesteryl ester for triglycerides between HDL and VLDL and LDL. We have published the first report indicating that a group of Japanese patients who were lacking CETP had extremely high HDL-C levels, low LDL-C levels and a low incidence of CHD. Animal studies, as well as clinical and epidemiologic evidences, have suggested that inhibition of CETP provides an effective strategy to raise HDL-C and reduce LDL-C levels. Four CETP inhibitors have substantially increased HDL-C levels in dyslipidemic patients. This review will discuss the current status and future prospects of CETP inhibitors in the treatment of CHD. At present anacetrapib by Merck and evacetrapib by Eli Lilly are under development. By 100mg of anacetrapib HDL-C increased by 138%, and LDL-C decreased by 40%. Evacetrapib 500 mg also showed dramatic 132% increase of HDL-C, while LDL-C decreased by 40%. If larger, long-term, randomized, clinical end point trials could corroborate other findings in reducing atherosclerosis, CETP inhibitors could have a significant impact in the management of dyslipidemic CHD patients. Inhibition of CETP synthesis by antisense oligonucleotide or small molecules will produce more similar conditions to human CETP deficiency and may be effective in reducing atherosclerosis and cardiovascular events. We are expecting the final data of prospective clinical trials by CETP inhibitors in 2015.

Solvent dependency of pentacene degradation for top-gate-type organic ferroelectric memory

Mabuchi, T.,Yoon, S.M.,Ishiwara, H. Elsevier 2011 Current Applied Physics Vol.11 No.4

To minimize the degradation of pentacene films in the fabrication of top-gate-type MFS FETs (metal-ferroelectric-semiconductor field-effect transistors), the characteristics of four solvents which are used for overcoating organic ferroelectric films on pentacene films are investigated by dipping pentacene MOS diodes in these solvents. Then, using appropriate solvents such as 1,4-dioxane, MFS diodes composed of Au, P(VDF-TrFE) (poly(vinylidene fluoride-trifluoroethylene)), and pentacene are fabricated, and then C-V (capacitance vs. voltage) characteristics are investigated. It is concluded from comparison of C-V and data retention characteristics of the top- and bottom-gate-type MFS diodes that degradation of the pentacene film is insignificant when an appropriate solvent is used.

일본어의 계통과 한국어

Mabuchi, Kazuo 한국일어일문학회 1999 日語日文學硏究 Vol.35 No.1

Fluorescence Behavior of Benzo[f]Quinoline Doped In Lpd Silica Thin Films

Mabuchi, Toshiaki,Suzuki, Satoshi,Nakajima, Tsuyoshi,Ino, Juichi,Takemura, Kazuo,Shimizu, Etsuro Korean Society of Photoscience 1998 Journal of Photosciences Vol.5 No.3

By using the liquid -phase-deposition (LPD) process, which has a potetnial of preparing organic inorganic composite materials, samples doped with benzo[f]quinoline (BfQ)into silica thia films wre prepared. We observed the fluorescene and fluorescene excitation spectra of the samples, as well as the fluorescence lifetimes and time-resoluved fluorescence spectra. The comparison of thefluorescence spectra in pH-controlled buffer solutions yields the results that the dominant species of BfQ in the LPD silica films is a protonated one. The fluorescence band assigned to a hydrogen-bonded species was observed on the samples prepared from the dipping solutions of 3 and 2 M hexafluorosilicic acid. The band assignment was confirmed by the fluorescence lifetime measurement. The FT-IR M hexaflurosilicic acid. The band assignment was confirmed by the flurescence lifetime meausurement. The FT-IR data proved the existence of included water in silica films prepared from the LPD process. The appearance of the band corresponding to the hydrogen-bonded species within LPD silica phases was explained by the proesence of included water. Depending on the preparation conditions of LPD silica films, the band assigned to protonated species shows bad shifts in a wavenumber region between the peak of hydrogen-bonded and typical protonated species. This implies that there is some distribution of steric conformation of protonated species of BfQ interacting with adsorbing sites of LPD silica. The time -resolved fluorescence spectra suggest that some relaxation process is involved in the conformation of BfQ doped into the solid phase of LPD silica.

Chemoradiotherapy followed by consolidation chemotherapy involving paclitaxel and carboplatin and in FIGO stage IIIB/IVA cervical cancer patients

Seiji Mabuchi,Fumiaki Isohashi,Mika Okazawa,Fuminori Kitada,Shintaro Maruoka,Kazuhiko Ogawa,Tadashi Kimura 대한부인종양학회 2017 Journal of Gynecologic Oncology Vol.28 No.1

Objective: To evaluate the efficacy and toxicity of paclitaxel plus carboplatin (TC)-based concurrent chemoradiotherapy (CCRT) followed by consolidation chemotherapy in the International Federation of Gynecology and Obstetrics (FIGO) stage IIIB/IVA cervical cancer patients. Methods: We reviewed the medical records of FIGO stage IIIB/IVA cervical cancer patients (n=30) who had been intended to be treated with TC-based CCRT followed by consolidation chemotherapy (TC-CCRT-group) from April 2012–May 2016. Patients who had been treated with CCRT involving a single platinum agent (CCRT-group; n=52) or definitive radiotherapy alone (RT-group; n=74) from January 1997–September 2012 were also identified and used as historical controls. Survival was calculated using the Kaplan-Meier method and compared using the log-rank test. Results: Of the 30 patients included in the TC-CCRT-group, 22 patients (73.3%) completed the planned TC-based CCRT. The most frequently observed acute grade 3/4 hematological toxicities were leukopenia and neutropenia, and diarrhea was the most common acute grade 3/4 non-hematological toxicity. After a median follow-up of 35 months, 9 patients (30.0%) had developed recurrent disease. The patients’ estimated 3-year progression-free survival (PFS) and overall survival (OS) rates were 67.9% and 90.8%, respectively. In comparisons with historical control groups, the survival outcomes of TC-CCRT-group was significantly superior to CCRT-group in terms of OS (p=0.011) and significantly superior to RT-group in terms of both PFS (p=0.009) and OS (p<0.001). Conclusion: TC-based CCRT followed by consolidation chemotherapy is safe and effective. A randomized controlled study needs to be conducted to further evaluate the efficacy of this multimodal approach in this patient population.

Cholesteryl Ester Transfer Protein (CETP) Deficiency and CETP Inhibitors

Hiroshi Mabuchi,Atsushi Nohara,Akihiro Inazu 한국분자세포생물학회 2014 Molecules and cells Vol.37 No.11

Epidemiologic studies have shown that low-density lipoprotein cholesterol (LDL-C) is a strong risk factor, whilst high-density lipoprotein cholesterol (HDL-C) reduces the risk of coronary heart disease (CHD). Therefore, strategies to manage dyslipidemia in an effort to prevent or treat CHD have primarily attempted at decreasing LDL-C and raising HDL-C levels. Cholesteryl ester transfer protein (CETP) mediates the exchange of cholesteryl ester for triglycerides between HDL and VLDL and LDL. We have published the first report indicating that a group of Japanese patients who were lacking CETP had extremely high HDL-C levels, low LDL-C levels and a low incidence of CHD. Animal studies, as well as clinical and epidemiologic evidences, have suggested that inhibition of CETP provides an effective strategy to raise HDL-C and reduce LDL-C levels. Four CETP inhibitors have substantially increased HDL-C levels in dyslipidemic patients. This review will discuss the current status and future prospects of CETP inhibitors in the treatment of CHD. At present anacetrapib by Merck and evacetrapib by Eli Lilly are under development. By 100mg of anacetrapib HDL-C increased by 138%, and LDL-C decreased by 40%. Evacetrapib 500 mg also showed dramatic 132% increase of HDL-C, while LDL-C decreased by 40%. If larger, long-term, randomized, clinical end point trials could corroborate other findings in reducing atherosclerosis, CETP inhibitors could have a significant impact in the management of dyslipidemic CHD patients. Inhibition of CETP synthesis by antisense oligonucleotide or small molecules will produce more similar conditions to human CETP deficiency and may be effective in reducing atherosclerosis and cardiovascular events. We are expecting the final data of prospective clinical trials by CETP inhibitors in 2015.

The Development of Japanese Pulic Administration

( Masaru Mabuchi ) 한국행정학회 2013 한국행정학회 학술발표논문집 Vol.2013 No.-

Clear cell carcinoma of the ovary: Molecular insights and future therapeutic perspectives

( Seiji Mabuchi ) 대한산부인과학회 2016 서울심포지움 Vol.21 No.-

Extension of the interconnect cable between the pump and the controller for the radiation-hardened magnetically suspended compound molecular pump

Takuya MABUCHI,Mitsuru SAKURAI,Kaoru WADA,Junichiro KAMIYA,Yuya NAMEKAWA 한국진공학회 2016 한국진공학회 학술발표회초록집 Vol.2016 No.8

Clear cell carcinoma of the ovary: molecular insights and future therapeutic perspectives

Seiji Mabuchi,Toru Sugiyama,Tadashi Kimura 대한부인종양학회 2016 Journal of Gynecologic Oncology Vol.27 No.3

Clear cell carcinoma (CCC) of the ovary is known to show poorer sensitivity to chemotherapeuticagents and to be associated with a worse prognosis than the more common serousadenocarcinoma or endometrioid adenocarcinoma. To improve the survival of patients withovarian CCC, the deeper understanding of the mechanism of CCC carcinogenesis as well asthe efforts to develop novel treatment strategies in the setting of both front-line treatmentand salvage treatment for recurrent disease are needed. In this presentation, we firstsummarize the mechanism responsible for carcinogenesis. Then, we highlight the promisingtherapeutic targets in ovarian CCC and provide information on the novel agents which inhibitthese molecular targets. Moreover, we discuss on the cytotoxic anti-cancer agents that can bebest combined with targeted agents in the treatment of ovarian CCC.