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Photocurrent attenuation by a single polar-to-nonpolar point mutation of channelrhodopsin-2
Sugiyama, Yuka,Wang, Hongxia,Hikima, Takuya,Sato, Minami,Kuroda, Jun,Takahashi, Tetsuo,Ishizuka, Toru,Yawo, Hiromu Korean Society of Photoscience 2009 Photochemical & photobiological sciences Vol.8 No.3
Channelrhodopsin-2 (ChR2), one of the algal light-gated cation channel rhodopsins, contains five peculiar glutamic acid residues in the N-terminal region corresponding to the second to third transmembrane helices. Here we made systematic mutations of these polar amino acid residues of ChR2 into nonpolar alanine, and evaluated their photocurrent properties. Amongst them, the photocurrent generated by the E97A mutation, ChR2(E97A), was much smaller than expected from its expression. The ChR2(E97A) photocurrent was similar to wild-type ChR2 in the kinetic profiles, the reversal potential and the dependency to the light power density. Our results suggest that the residue E97 is one of the molecular determinants involved in the ion flux regulation.
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.
Shunsuke Ohnishi,Hidemichi Watari,Maki Kanno,Yoko Ohba,Satoshi Takeuchi,Tempei Miyaji,Shunsuke Oyamada,Eiji Nomura,Hidenori Kato,Toru Sugiyama,Masahiro Asaka,Noriaki Sakuragi,Takuhiro Yamaguchi,Yasuhi 대한부인종양학회 2017 Journal of Gynecologic Oncology Vol.28 No.5
Objective: Rikkunshito, an herbal medicine, is widely prescribed in Japan for the treatmentof anorexia and functional dyspepsia, and has been reported to recover reductions in foodintake caused by cisplatin. We investigated whether rikkunshito could improve chemotherapyinducednausea and vomiting (CINV) and anorexia in patients treated with cisplatin. Methods: Patients with uterine cervical or corpus cancer who were to receive cisplatin (50 mg/m2day 1) and paclitaxel (135 mg/m2day 0) as first-line chemotherapy were randomly assignedto the rikkunshito group receiving oral administration on days 0–13 with standard antiemetics,or the control group receiving antiemetics only. The primary endpoint was the rate of completecontrol (CC: no emesis, no rescue medication, and no significant nausea) in the overall phase(0–120 hours). Two-tailed p<0.20 was considered significant in the planned analysis. Results: The CC rate in the overall phase was significantly higher in the rikkunshito groupthan in the control group (57.9% vs. 35.3%, p=0.175), as were the secondary endpoints:the CC rate in the delayed phase (24–120 hours), and the complete response (CR) rates(no emesis and no rescue medication) in the overall and delayed phases (63.2% vs. 35.3%, p=0.095; 84.2% vs. 52.9%, p=0.042; 84.2% vs. 52.9%, p=0.042, respectively), and time totreatment failure (p=0.059). Appetite assessed by visual analogue scale (VAS) appeared to besuperior in the rikkunshito group from day 2 through day 6. Conclusion: Rikkunshito provided additive effect for the prevention of CINV and anorexia
Koji Matsuo,Muneaki Shimada,Tsuyoshi Saito,Kazuhiro Takehara,Hideki Tokunaga,Yoh Watanabe,Yukiharu Todo,Kenichirou Morishige,Mikio Mikami,Toru Sugiyama 대한부인종양학회 2018 Journal of Gynecologic Oncology Vol.29 No.1
Objective: To examine the surgical-pathological predictors of para-aortic lymph node (PAN) metastasis at radical hysterectomy, and for PAN recurrence among women who did not undergo PAN dissection at radical hysterectomy. Methods: This is a retrospective analysis of a nation-wide cohort study of surgically-treated stage IB–IIB cervical cancer (n=5,620). Multivariate models were used to identify independent surgical-pathological predictors for PAN metastasis/recurrence. Results: There were 120 (2.1%) cases of PAN metastasis at surgery with parametrial involvement (adjusted odds ratio [aOR]=1.65), deep stromal invasion (aOR=2.61), ovarian metastasis (aOR=3.10), and pelvic nodal metastasis (single-node aOR=5.39 and multiple-node aOR=33.5, respectively) being independent risk factors (all, p<0.05). Without any risk factors, the incidence of PAN metastasis was 0.9%, while women exhibiting certain risk factor patterns (>20% of the study population) had PAN metastasis incidences of ≥4%. Among 4,663 clinically PAN-negative cases at surgery, PAN recurrence was seen in 195 (4.2%) cases that was significantly higher than histologically PAN-negative cases (2.5%, p=0.046). In clinically PAN-negative cases, parametrial involvement (adjusted hazard ratio [aHR]=1.67), lympho-vascular space invasion (aHR=1.95), ovarian metastasis (aHR=2.60), and pelvic lymph node metastasis (single-node aHR=2.49 and multiple-node aHR=8.11, respectively) were independently associated with increased risk of PAN recurrence (all, p<0.05). Without any risk factors, 5-year PAN recurrence risk was 0.8%; however, women demonstrating certain risk factor patterns (>15% of the clinically PAN-negative population) had 5-year PAN recurrence risks being ≥8%. Conclusion: Surgical-pathological risk factors proposed in this study will be useful to identify women with increased risk of PAN metastasis/recurrence.
Takashi Motohashi,Akira Yabuno,Hiroshi Michimae,Tetsuro Ohishi,Miwa Nonaka,Masashi Takano,Shin Nishio,Hiroyuki Fujiwara,Keiichi Fujiwara,Eiji Kondo,Toru Sugiyama,Tsutomu Tabata 대한부인종양학회 2021 Journal of Gynecologic Oncology Vol.32 No.1
Objective: The standard dose for pegylated liposomal doxorubicin (PLD) is 50 mg/m2every 4weeks. While 40 mg/m2has recently been used in clinical practice, evidence supporting thisuse remains lacking. Methods: This phase III randomized, non-inferiority study compared progression free survival (PFS) for patients with platinum-resistant ovarian carcinoma between anexperimental arm (40 mg/m2PLD) and a standard arm (50 mg/m2PLD) until 10 courses,disease progression or unacceptable toxicity. Eligible patients had received ≤2 prior lines. Stratification was by performance status and PFS of prior chemotherapy (<3 months versus ≥3months). The primary endpoint was PFS and secondary endpoints were overall survival (OS),toxicity profile, clinical response and tolerability. The total number of patients was 470. Results: The trial was prematurely closed due to slow recruitment, with 272 patients randomizedto the experimental arm (n=137) and standard arm (n=135). Final analysis was performed with234 deaths and 269 events for PFS. In the experimental arm vs. standard arm, median PFS was4.0 months vs. 4.0 months (hazard ratio [HR]=1.065; 95% confidence interval [CI]=0.830–1.366)and median OS was 14.0 months vs. 14.0 months (HR=1.078; 95% CI=0.831–1.397). Hematologictoxicity and oral cavity mucositis (≥grade 2) were more frequent in the standard arm than in theexperimental arm, but no difference was seen in ≥grade 2 hand-foot skin reaction. Conclusion: Non-inferiority of 2 PLD dosing schedule was not confirmed because the trialwas closed prematurely. However, recommendation of dose reduction of PLD should bebased both on efficacy and safety. Trial Registration: UMIN Clinical Trials Registry Identifier: UMIN000003130