253 results on '"Ichiro Yamato"'
Search Results
2. Giant splenic artery aneurysm rupture into the stomach that was successfully managed with emergency distal pancreatectomy
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Chihiro Yoshikawa, Ichiro Yamato, Yasuyuki Nakata, Tadashi Nakagawa, Takashi Inoue, Mitsuhiro Nakatani, Daiki Nezu, Syunsuke Doi, Yasuhiro Kuroda, Kazuki Fujii, Syouhei Kishida, Midori Kamikubo, and Saiho Ko
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Splenic artery aneurysm ,Upper gastrointestinal bleeding ,Hemorrhagic shock ,Emergency surgery ,Case report ,Surgery ,RD1-811 - Abstract
Abstract Background Splenic artery aneurysms usually rupture into the free peritoneal space and rarely into the gastrointestinal tract. We report the case of a patient with a giant splenic artery aneurysm that ruptured in to the stomach with hemorrhagic shock and was successfully treated with emergency surgery. Case presentation A 59-year-old man presented to the emergency department with chest pain and syncope. Contrast-enhanced computed tomography showed splenic artery aneurysm with active contrast extravasation. He developed upper gastrointestinal (UGI) bleeding and hypovolemic shock. We diagnosed a splenic artery aneurysm ruptured in to the stomach, performed emergency distal splenopancreatectomy including the aneurysm and partial gastric resection, and could prevent patient death. Conclusions This report shows that splenic artery aneurysm can cause UGI bleeding. Thus, clinicians should be alert about this condition when managing patients with UGI bleeding and/or splenic artery aneurysm.
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- 2022
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3. Adaptive Dynamics Simulation of Interference Phenomenon for Physical and Biological Systems
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Tadashi Ando, Masanari Asano, Andrei Khrennikov, Takashi Matsuoka, and Ichiro Yamato
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two-slit interference ,adaptive dynamics ,interaction network ,quantum mechanics ,particle model simulation ,Science ,Astrophysics ,QB460-466 ,Physics ,QC1-999 - Abstract
Biological systems have been shown to have quantum-like behaviors by applying the adaptive dynamics view on their interaction networks. In particular, in the process of lactose–glucose metabolism, cells generate probabilistic interference patterns similarly to photons in the two-slit experiment. Such quantum-like interference patterns can be found in biological data, on all scales, from proteins to cognitive, ecological, and social systems. The adaptive dynamics approach covers both biological and physical phenomena, including the ones which are typically associated with quantum physics. We guess that the adaptive dynamics can be used for the clarification of quantum foundations, and the present paper is the first step in this direction. We suggest the use of an algorithm for the numerical simulation of the behavior of a billiard ball-like particle passing through two slits by explicitly considering the influence of the two-slit environment (experimental context). Our simulation successfully mimics the interference pattern obtained experimentally in quantum physics. The interference of photons or electrons by two slits is known as a typical quantum mechanical effect. We do not claim that the adaptive dynamics can reproduce the whole body of quantum mechanics, but we hope that this numerical simulation example will stimulate further extensive studies in this direction—the representation of quantum physical phenomena in an adaptive dynamical framework.
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- 2023
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4. Correction: Giant splenic artery aneurysm rupture into the stomach that was successfully managed with emergency distal pancreatectomy
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Chihiro Yoshikawa, Ichiro Yamato, Yasuyuki Nakata, Tadashi Nakagawa, Takashi Inoue, Mitsuhiro Nakatani, Daiki Nezu, Shunsuke Doi, Yasuhiro Kuroda, Kazuki Fujii, Shouhei Kishida, Midori Kamikubo, and Saiho Ko
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Surgery ,RD1-811 - Published
- 2022
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5. Rotational Mechanism Model of the Bacterial V1 Motor Based on Structural and Computational Analyses
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Abhishek Singharoy, Chris Chipot, Toru Ekimoto, Kano Suzuki, Mitsunori Ikeguchi, Ichiro Yamato, and Takeshi Murata
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rotary motor ,V-ATPase ,X-ray structure ,molecular dynamics ,free energy ,Physiology ,QP1-981 - Abstract
V1-ATPase exemplifies the ubiquitous rotary motor, in which a central shaft DF complex rotates inside a hexagonally arranged catalytic A3B3 complex, powered by the energy from ATP hydrolysis. We have recently reported a number of crystal structures of the Enterococcus hirae A3B3DF (V1) complex corresponding to its nucleotide-bound intermediate states, namely the forms waiting for ATP hydrolysis (denoted as catalytic dwell), ATP binding (ATP-binding dwell), and ADP release (ADP-release dwell) along the rotatory catalytic cycle of ATPase. Furthermore, we have performed microsecond-scale molecular dynamics simulations and free-energy calculations to investigate the conformational transitions between these intermediate states and to probe the long-time dynamics of the molecular motor. In this article, the molecular structure and dynamics of the V1-ATPase are reviewed to bring forth a unified model of the motor’s remarkable rotational mechanism.
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- 2019
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6. Crystal structures of the ATP-binding and ADP-release dwells of the V1 rotary motor
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Kano Suzuki, Kenji Mizutani, Shintaro Maruyama, Kazumi Shimono, Fabiana L. Imai, Eiro Muneyuki, Yoshimi Kakinuma, Yoshiko Ishizuka-Katsura, Mikako Shirouzu, Shigeyuki Yokoyama, Ichiro Yamato, and Takeshi Murata
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Science - Abstract
V1-ATPases are rotary molecular motors that are powered by ATP hydrolysis. Here, the authors report two of the missing rotary states of this protein complex, and perform biochemical analysis to investigate the binding mode of the nucleotides.
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- 2016
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7. Biochemical and biophysical properties of interactions between subunits of the peripheral stalk region of human V-ATPase.
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Suhaila Rahman, Ichiro Yamato, Shinya Saijo, Kenji Mizutani, Yoshiko Ishizuka-Katsura, Noboru Ohsawa, Takaho Terada, Mikako Shirouzu, Shigeyuki Yokoyama, So Iwata, and Takeshi Murata
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Medicine ,Science - Abstract
Peripheral stalk subunits of eukaryotic or mammalian vacuolar ATPases (V-ATPases) play key roles in regulating its assembly and disassembly. In a previous study, we purified several subunits and their isoforms of the peripheral stalk region of Homo sapiens (human) V-ATPase; such as C1, E1G1, H, and the N-terminal cytoplasmic region of V(o), a1. Here, we investigated the in vitro binding interactions of the subunits at the stalk region and measured their specific affinities. Surface plasmon resonance experiments revealed that the subunit C1 binds the E1G1 heterodimer with both high and low affinities (2.8 nM and 1.9 µM, respectively). In addition, an E1G1-H complex can be formed with high affinity (48 nM), whereas affinities of other subunit pairs appeared to be low (∼0.21-3.0 µM). The putative ternary complex of C1-H-E1G1 was not much strong on co-incubation of these subunits, indicating that the two strong complexes of C1-E1G1 and H-E1G1 in cooperation with many other weak interactions may be sufficiently strong enough to withstand the torque of rotation during catalysis. We observed a partially stable quaternary complex (consisting of E1G1, C1, a1(NT), and H subunits) resulting from discrete peripheral subunit interactions stabilizing the complex through their intrinsic affinities. No binding was observed in the absence of E1G1 (using only H, C1, and a1(NT)); therefore, it is likely that, in vivo, the E1G1 heterodimer has a significant role in the initiation of subunit assembly. Multiple interactions of variable affinity in the stalk region may be important to the mechanism of reversible dissociation of the intact V-ATPase.
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- 2013
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8. Loose binding of the DF axis with the A3B3 complex stimulates the initial activity of Enterococcus hirae V1-ATPase.
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Md Jahangir Alam, Satoshi Arai, Shinya Saijo, Kano Suzuki, Kenji Mizutani, Yoshiko Ishizuka-Katsura, Noboru Ohsawa, Takaho Terada, Mikako Shirouzu, Shigeyuki Yokoyama, So Iwata, Yoshimi Kakinuma, Ichiro Yamato, and Takeshi Murata
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Medicine ,Science - Abstract
Vacuolar ATPases (V-ATPases) function as proton pumps in various cellular membrane systems. The hydrophilic V1 portion of the V-ATPase is a rotary motor, in which a central-axis DF complex rotates inside a hexagonally arranged catalytic A3B3 complex by using ATP hydrolysis energy. We have previously reported crystal structures of Enterococcushirae V-ATPase A3B3 and A3B3DF (V1) complexes; the result suggested that the DF axis induces structural changes in the A3B3 complex through extensive protein-protein interactions. In this study, we mutated 10 residues at the interface between A3B3 and DF complexes and examined the ATPase activities of the mutated V1 complexes as well as the binding affinities between the mutated A3B3 and DF complexes. Surprisingly, several V1 mutants showed higher initial ATPase activities than wild-type V1-ATPase, whereas these mutated A3B3 and DF complexes showed decreased binding affinities for each other. However, the high ATP hydrolysis activities of the mutants decreased faster over time than the activity of the wild-type V1 complex, suggesting that the mutants were unstable in the reaction because the mutant A3B3 and DF complexes bound each other more weakly. These findings suggest that strong interaction between the DF complex and A3B3 complex lowers ATPase activity, but also that the tight binding is responsible for the stable ATPase activity of the complex.
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- 2013
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9. Data from Overexpression of PD-L1 Significantly Associates with Tumor Aggressiveness and Postoperative Recurrence in Human Hepatocellular Carcinoma
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Jia Fan, Yang Xu, Yong-Sheng Xiao, Ying-Hong Shi, Bai-Zhou Li, Jian Zhou, Yoshiyuki Nakajima, Masayuki Sho, Ichiro Yamato, Shuang-Jian Qiu, Xiao-Ying Wang, and Qiang Gao
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Purpose: The aberrant expression of programmed cell death 1 ligands 1 and 2 (PD-Ls) on tumor cells dampens antitumor immunity, resulting in tumor immune evasion. In this study, we investigated the expression of PD-Ls in human hepatocellular carcinoma (HCC) to define their prognostic significance after curative surgery.Experimental Design: Immunohistochemistry was used to investigate PD-Ls expression as well as granzyme B+ cytotoxic and FoxP3+ regulatory T cell infiltration on tissue microarrays containing 240 randomly selected HCC patients who underwent surgery. The results were further verified in an independent cohort of 125 HCC patients. PD-Ls expression on HCC cell lines was detected by Western blot assay.Results: Patients with higher expression of PD-L1 had a significantly poorer prognosis than patients with lower expression. Although patients with higher expression of PD-L2 also had a poorer survival, the difference in recurrence was not statistically significant. Multivariate analysis identified tumor expression of PD-L1 as an independent predictor for postoperative recurrence. No correlation was found between PD-Ls expression and granzyme B+ lymphocyte infiltration, whereas a significant positive correlation was detected between PD-Ls expression and FoxP3+ lymphocyte infiltration. In addition, tumor-infiltrating cytotoxic and regulatory T cells were also independent prognosticators for both survival and recurrence. The prognostic value of PD-L1 expression was validated in the independent data set.Conclusion: Our data suggest for the first time that PD-L1 status may be a new predictor of recurrence for HCC patients and provide the rationale for developing a novel therapy of targeting the PD-L1/PD-1 pathway against this fatal malignancy.
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- 2023
10. Supplementary Data from Overexpression of PD-L1 Significantly Associates with Tumor Aggressiveness and Postoperative Recurrence in Human Hepatocellular Carcinoma
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Jia Fan, Yang Xu, Yong-Sheng Xiao, Ying-Hong Shi, Bai-Zhou Li, Jian Zhou, Yoshiyuki Nakajima, Masayuki Sho, Ichiro Yamato, Shuang-Jian Qiu, Xiao-Ying Wang, and Qiang Gao
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Supplementary Data from Overexpression of PD-L1 Significantly Associates with Tumor Aggressiveness and Postoperative Recurrence in Human Hepatocellular Carcinoma
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- 2023
11. Application of Non-Kolmogorovian Probability and Quantum Adaptive Dynamics to Unconscious Inference in Visual Perception Process.
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Luigi Accardi, Andrei Yu. Khrennikov, Masanori Ohya, Yoshiharu Tanaka, and Ichiro Yamato
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- 2016
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12. Lamarckian Evolution of Epigenome from Open Quantum Systems and Entanglement.
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Masanari Asano, Irina Basieva, Andrei Yu. Khrennikov, Masanori Ohya, Yoshiharu Tanaka, and Ichiro Yamato
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- 2013
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13. Adaptive Dynamics and Its Application to Context Dependent Systems Breaking the Classical Probability Law.
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Masanari Asano, Irina Basieva, Andrei Yu. Khrennikov, Masanori Ohya, Yoshiharu Tanaka, and Ichiro Yamato
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- 2012
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14. A Quantum-Like Model of Escherichia coli's Metabolism Based on Adaptive Dynamics.
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Masanari Asano, Irina Basieva, Andrei Yu. Khrennikov, Masanori Ohya, Yoshiharu Tanaka, and Ichiro Yamato
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- 2012
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15. Quantum-Like Paradigm: From Molecular Biology to Cognitive Psychology.
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Masanari Asano, Masanori Ohya, Yoshiharu Tanaka, Ichiro Yamato, Irina Basieva, and Andrei Yu. Khrennikov
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- 2011
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16. An affinity change model to elucidate the rotation mechanism of V1-ATPase
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Ichiro Yamato, Satoshi Arai, Mitsunori Shiroishi, Shintaro Maruyama, and Takeshi Murata
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0301 basic medicine ,biology ,Chemistry ,ATPase ,Protein subunit ,Biophysics ,Cell Biology ,Crystal structure ,biology.organism_classification ,Biochemistry ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,Membrane ,ATP hydrolysis ,Enterococcus hirae ,030220 oncology & carcinogenesis ,biology.protein ,V-ATPase ,Surface plasmon resonance ,Molecular Biology - Abstract
V-ATPases are ubiquitous proton-transporting ATPases of eukaryotic and prokaryotic membranes that utilize energy from ATP hydrolysis. The hydrophilic catalytic part called V1-ATPase is composed of a ring-shaped hexametric A3B3 complex and a central DF shaft. We previously proposed a rotation mechanism of the Enterococcus hirae V1-ATPase based on the crystal structures of the V1 and A3B3 complexes. However, the driving force that induces the conformational changes of A3B3 and rotation of the DF shaft remains unclear. In this study, we investigated the binding affinity changes between subunits of V1-ATPase by surface plasmon resonance analysis. The binding of ATP to subunit A was found to considerably increase the affinity between the A and B subunits, and thereby ATP binding contributes to forming the A1B1 tight conformation. Furthermore, the DF shaft bound to the reconstituted A1B1 complex with high affinity, suggesting that the tight A1B1 complex is a major binding unit of the shaft in the A3B3 ring complex. Based on these results, we propose that rotation of the V1-ATPase is driven by affinity changes between each subunit via thermal fluctuations.
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- 2020
17. Review of: 'Revealing a hidden intermediate of rotatory catalysis with X-ray crystallography and Molecular simulations'
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ichiro yamato
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- 2021
18. Giant splenic artery aneurysm rupture into the stomach that was successfully managed with emergency distal pancreatectomy
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Chihiro Yoshikawa, Ichiro Yamato, Yasuyuki Nakata, Tadashi Nakagawa, Takashi Inoue, Mitsuhiro Nakatani, Daiki Nezu, Shunsuke Doi, Yasuhiro Kuroda, Kazuki Fujii, Shouhei Kishida, Midori Kamikubo, and Saiho Ko
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General Economics, Econometrics and Finance - Abstract
Background Splenic artery aneurysms usually rupture into the free peritoneal space and rarely into the gastrointestinal tract. We report the case of a patient with a giant splenic artery aneurysm that ruptured in to the stomach with hemorrhagic shock and was successfully treated with emergency surgery. Case presentation A 59-year-old man presented to the emergency department with chest pain and syncope. Contrast-enhanced computed tomography showed splenic artery aneurysm with active contrast extravasation. He developed upper gastrointestinal (UGI) bleeding and hypovolemic shock. We diagnosed a splenic artery aneurysm ruptured in to the stomach, performed emergency distal splenopancreatectomy including the aneurysm and partial gastric resection, and could prevent patient death. Conclusions This report shows that splenic artery aneurysm can cause UGI bleeding. Thus, clinicians should be alert about this condition when managing patients with UGI bleeding and/or splenic artery aneurysm.
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- 2021
19. An affinity change model to elucidate the rotation mechanism of V
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Satoshi, Arai, Shintaro, Maruyama, Mitsunori, Shiroishi, Ichiro, Yamato, and Takeshi, Murata
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Adenosine Diphosphate ,Models, Molecular ,Protein Subunits ,Vacuolar Proton-Translocating ATPases ,Adenosine Triphosphate ,Rotation ,Protein Conformation ,Recombinant Fusion Proteins ,Surface Plasmon Resonance - Abstract
V-ATPases are ubiquitous proton-transporting ATPases of eukaryotic and prokaryotic membranes that utilize energy from ATP hydrolysis. The hydrophilic catalytic part called V
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- 2020
20. Energy and information flows in biological systems: Bioenergy transduction of V 1 -ATPase rotary motor and dynamics of thermodynamic entropy in information flows
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Takeshi Murata, Ichiro Yamato, and Andrei Khrennikov
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0301 basic medicine ,Biophysics ,Thermodynamics ,Rotary engine ,03 medical and health sciences ,V1 atpase ,Chemical energy ,030104 developmental biology ,Bioenergy ,Molecular mechanism ,Biological system ,Molecular Biology ,Quantum ,Mechanical energy ,Mathematics - Abstract
We classify research fields in biology with respect to flows of materials, energy, and information. We investigate energy transducing mechanisms in biology, using as a representative the typical molecular rotary motor V1-ATPase from a bacterium Enterococcus hirae. The structures of several intermediates of the rotary motor are described and the molecular mechanism of the motor converting chemical energy into mechanical energy is discussed. Comments and considerations on the information flows in biology, especially on the thermodynamic entropy in quantum physical and biological systems, are presented in section 3 in a biologist friendly manner.
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- 2017
21. A model of differentiation in quantum bioinformatics
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Andrei Khrennikov, Ichiro Yamato, Masanari Asano, and Irina Basieva
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0301 basic medicine ,Physics ,Quantum decoherence ,Biophysics ,Computational Biology ,Models, Theoretical ,Bioinformatics ,03 medical and health sciences ,Formalism (philosophy of mathematics) ,Theoretical physics ,030104 developmental biology ,Animals ,Quantum Theory ,Temporal change ,Molecular Biology ,Quantum - Abstract
Differentiation is a universal process found in various phenomena of nature. As seen in the example of cell differentiation, the creation diversity on individual's character is caused by environmental interactions. In this paper, we try to explain its mechanism, which has been discussed mainly in Biology, by using the formalism of quantum physics. Our approach known as quantum bioinformatics shows that the temporal change of statistical state called decoherence fits to describe non-local phenomena like differentiation.
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- 2017
22. Intraarterial Therapy Using Micellar Nanoparticles Incorporating SN-38 in a Rabbit Liver Tumor Model
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Yasushi Fukuoka, Hideyuki Nishiofuku, Takeshi Sato, Shota Tatsumoto, Chiho Ohbayashi, Kimihiko Kichikawa, Ichiro Yamato, Masayuki Sho, Shigeru Matsushima, Toshihiro Tanaka, Masato Takano, Tetsuya Masada, and Satoshi Yasuda
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Pathology ,medicine.medical_specialty ,Liver tumor ,Necrosis ,Drug Compounding ,Femoral vein ,Urology ,H&E stain ,Antineoplastic Agents ,Apoptosis ,SN-38 ,Irinotecan ,030218 nuclear medicine & medical imaging ,03 medical and health sciences ,chemistry.chemical_compound ,Hepatic Artery ,Liver Neoplasms, Experimental ,0302 clinical medicine ,Pharmacokinetics ,medicine ,Animals ,Infusions, Intra-Arterial ,Tissue Distribution ,Radiology, Nuclear Medicine and imaging ,Infusions, Intravenous ,Micelles ,Drug Carriers ,business.industry ,Femoral Vein ,medicine.disease ,chemistry ,Area Under Curve ,030220 oncology & carcinogenesis ,Nanoparticles ,Camptothecin ,Female ,Rabbits ,medicine.symptom ,Cardiology and Cardiovascular Medicine ,Drug carrier ,business ,medicine.drug - Abstract
Purpose To evaluate the pharmacokinetics of intraarterial (IA) administration of micellar nanoparticles incorporating SN-38 injection compared with intravenous (IV) administration in a rabbit liver tumor model. Materials and Methods In this animal care committee–approved study, 18 rabbits (mean weight, 3.89 kg; range, 3.20–4.70 kg) with VX2 liver tumors were divided into two groups (IA and IV). Micellar nanoparticles incorporating SN-38 (30 mg/kg) were injected through the left hepatic artery in the IA group and the right femoral vein in the IV group. NK012 and free SN-38 in the plasma, liver parenchyma, and tumors were measured within 24 hours. Histologic examinations were conducted at 2 and 24 hours. Results There were no significant differences in the serum area under the concentration–time curve (0–24 h) for free SN-38, at 1,500 and 1,310 μg∙min/mL in the IA and IV groups, respectively ( P = .152). The IA group showed significantly higher free SN-38 concentrations in tumor tissues at all time points compared with the IV group ( P = .002 at 3 min, P = .011 at 2 h, and P = .047 at 24 h). Histologic findings showed that significantly higher tumor necrosis ratios were observed in the IA group compared with the IV group at 24 hours ( P = .028). Conclusions Micellar nanoparticles could be a promising IA drug delivery system to achieve high tumor tissue concentrations of SN-38.
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- 2017
23. Rotation Mechanism of Molecular Motor V1-ATPase Studied by Multiscale Molecular Dynamics Simulation
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Yuta Isaka, Toru Ekimoto, Yuichi Kokabu, Ichiro Yamato, Mitsunori Ikeguchi, and Takeshi Murata
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0301 basic medicine ,Steric effects ,Chemistry ,Biophysics ,Random hexamer ,Rotation ,Ring (chemistry) ,03 medical and health sciences ,Molecular dynamics ,Crystallography ,030104 developmental biology ,0302 clinical medicine ,Stalk ,ATP hydrolysis ,Molecular motor ,030217 neurology & neurosurgery - Abstract
Enterococcus hirae V 1 -ATPase is a molecular motor composed of the A 3 B 3 hexamer ring and the central stalk. In association with ATP hydrolysis, three catalytic AB pairs in the A 3 B 3 ring undergo conformational changes, which lead to a 120° rotation of the central stalk. To understand how the conformational changes of three catalytic pairs induce the 120° rotation of the central stalk, we performed multiscale molecular dynamics (MD) simulations in which coarse-grained and all-atom MD simulations were combined using a fluctuation matching methodology. During the rotation, a catalytic AB pair spontaneously adopted an intermediate conformation, which was not included in the initial inputs of the simulations and was essentially close to the "bindable-like" structure observed in a recently solved crystal structure. Furthermore, the creation of a space between the bindable-like and tight pairs was required for the central stalk to rotate without steric hindrance. These cooperative rearrangements of the three catalytic pairs are crucial for the rotation of the central stalk.
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- 2017
24. Metastable asymmetrical structure of a shaftless V 1 motor
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Takayuki Uchihashi, Ichiro Yamato, Fabiana L. Imai, Yoshiko Ishizuka-Katsura, Takeshi Murata, Mikako Shirouzu, Motonori Imamura, Kano Suzuki, Hideyuki Matsunami, Kenji Mizutani, Hikaru Sasaki, Shintaro Maruyama, Tomomi Kimura-Someya, Toshio Ando, and Yasuko Saito
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0303 health sciences ,Multidisciplinary ,biology ,Chemistry ,Mutant ,Wild type ,biology.organism_classification ,3. Good health ,03 medical and health sciences ,Barrel ,Crystallography ,0302 clinical medicine ,Protein structure ,Enterococcus hirae ,Hydrolase ,Binding site ,Conformational isomerism ,030217 neurology & neurosurgery ,030304 developmental biology - Abstract
V1-ATPase is an ATP-driven rotary motor that is composed of a ring-shaped A3B3 complex and a central DF shaft. The nucleotide-free A3B3 complex of Enterococcus hirae, composed of three identical A1B1 heterodimers, showed a unique asymmetrical structure, probably due to the strong binding of the N-terminal barrel domain, which forms a crown structure. Here, we mutated the barrel region to weaken the crown, and performed structural analyses using high-speed atomic force microscopy and x-ray crystallography of the mutant A3B3. The nucleotide-free mutant A3B3 complex had a more symmetrical open structure than the wild type. Binding of nucleotides produced a closely packed spiral-like structure with a disrupted crown. These findings suggest that wild-type A3B3 forms a metastable (stressed) asymmetric structure composed of unstable A1B1 conformers due to the strong constraint of the crown. The results further the understanding of the principle of the cooperative transition mechanism of rotary motors.
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- 2019
25. The prognosis of liver resection for patients with four or more colorectal liver metastases has not improved in the era of modern chemotherapy
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Takeo Nomi, Yoshiyuki Nakajima, Daisuke Hokuto, Ichiro Yamato, Chihiro Kawaguchi, Hiromichi Kanehiro, Satoshi Yasuda, Takahiro Yoshikawa, Takatsugu Yamada, and Shinsaku Obara
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Oncology ,medicine.medical_specialty ,Chemotherapy ,Multivariate analysis ,biology ,business.industry ,Colorectal cancer ,medicine.medical_treatment ,General Medicine ,medicine.disease ,Resection ,Cancer antigen ,03 medical and health sciences ,0302 clinical medicine ,Carcinoembryonic antigen ,030220 oncology & carcinogenesis ,Internal medicine ,Perioperative chemotherapy ,biology.protein ,Overall survival ,Medicine ,030211 gastroenterology & hepatology ,Surgery ,business - Abstract
BACKGROUND AND OBJECTIVES The impact of perioperative chemotherapy on patients with multiple colorectal liver metastases (CRLM) remains unclear. We attempted to examine whether the introduction of modern chemotherapies has improved the prognosis of patients that undergo liver resection for ≥4 CRLM. METHODS Between January 1990 and December 2013, 194 patients underwent liver resection for CRLM at our institution. The outcomes of the patients with ≥4 and 1-3 CRLM were compared before and after 2005, when modern chemotherapies were introduced to Japan. RESULTS There were 50 and 144 patients with ≥4 (Group 1) and 1-3 (Group 2) CRLM, respectively. The overall survival (OS) rate of Group 1 was significantly worse than that of Group 2 (P = 0.0007). The OS rate of Group 2 was significantly better after 2005 than before 2004 (P = 0.039), while no such differences were observed in Group 1. Multivariate analysis identified three prognostic factors in Group 1: a serum carcinoembryonic antigen level of ≥20 ng/ml (P = 0.018), a serum cancer antigen 19-9 level of ≥100 U/ml (P = 0.018), and a primary colorectal cancer N factor of ≥N2 (P = 0.023). CONCLUSIONS The prognosis of patients with ≥4 CRLM that undergo liver resection has not improved despite the development of modern chemotherapies. J. Surg. Oncol. 2016;114:959-965. © 2016 Wiley Periodicals, Inc.
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- 2016
26. Laparoscopic resection of a hepatic mucinous cystic neoplasm: A case report
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Satoshi Yasuda, Chihiro Kawaguchi, Shinsaku Obara, Yoshiyuki Nakajima, Satoshi Nishiwada, Takahiro Yoshikawa, Takatsugu Yamada, Hiromichi Kanehiro, Daisuke Hokuto, Takeo Nomi, and Ichiro Yamato
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medicine.medical_specialty ,medicine.diagnostic_test ,business.industry ,General surgery ,Case Report ,Mucinous cystic neoplasm ,Laparoscopic liver resection ,030230 surgery ,Ovarian like stroma ,Cystic Neoplasm ,03 medical and health sciences ,0302 clinical medicine ,Liver ,medicine ,Ovarian-like stroma ,030211 gastroenterology & hepatology ,Surgery ,Laparoscopic resection ,Laparoscopy ,business - Abstract
Highlights • The first report of a hepatic mucinous cystic neoplasm (MCN-H) completely resected by laparoscopy. • MCN-H has been reported to have the potential for malignancy, and recommended to resection. • Benign liver lesions including MCN-H are commonly observed in young females and lacparoscopic liver resection might have cosmetic advantages for patients., Introduction We aimed to present a case of hepatic mucinous cystic neoplasm (MCN-H) that was completely resected by laparoscopy. Presentation of case A 47-year-old female exhibited mild elevation of serum liver enzyme levels. Abdominal computed tomography revealed a 45-mm multilocular cystic tumor in segment IV of the liver, along with intermittent border calcification and minimal wall thickness. Magnetic resonance imaging revealed fluid-to-fluid level in the cystic tumor, thereby increasing the suspicion of a mild hemorrhage. The patient underwent laparoscopic liver resection (LLR) with a diagnosis of suspected mucinous cystic neoplasm of the liver. The entire tumor was successfully resected with a laparoscopic approach. The resected specimen was a 4.2 × 3.3 × 2.2-cm cystic tumor. Histological findings revealed mucin-producing singular epithelium and ovarian-like stroma. The tumor was diagnosed as a MCN-H with no malignancy. Discussion This is the first report in which a MCN-H was completely resected by laparoscopy. MCN-H is rare and is observed in only
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- 2016
27. Operating principles of rotary molecular motors: differences between F1 and V1 motors
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Ichiro Yamato, Takeshi Murata, and Yoshimi Kakinuma
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0301 basic medicine ,chemistry.chemical_classification ,Stereochemistry ,General Medicine ,Crystal structure ,Catalysis ,Mechanism (engineering) ,03 medical and health sciences ,030104 developmental biology ,chemistry ,F-ATPase ,Molecular mechanism ,Molecular motor ,Nucleotide - Abstract
Among the many types of bioenergy-transducing machineries, F- and V-ATPases are unique bio- and nano-molecular rotary motors. The rotational catalysis of F1-ATPase has been investigated in detail, and molecular mechanisms have been proposed based on the crystal structures of the complex and on extensive single-molecule rotational observations. Recently, we obtained crystal structures of bacterial V1-ATPase (A3B3 and A3B3DF complexes) in the presence and absence of nucleotides. Based on these new structures, we present a novel model for the rotational catalysis mechanism of V1-ATPase, which is different from that of F1-ATPases.
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- 2016
28. Metastable asymmetrical structure of a shaftless V
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Shintaro, Maruyama, Kano, Suzuki, Motonori, Imamura, Hikaru, Sasaki, Hideyuki, Matsunami, Kenji, Mizutani, Yasuko, Saito, Fabiana L, Imai, Yoshiko, Ishizuka-Katsura, Tomomi, Kimura-Someya, Mikako, Shirouzu, Takayuki, Uchihashi, Toshio, Ando, Ichiro, Yamato, and Takeshi, Murata
- Subjects
Vacuolar Proton-Translocating ATPases ,Binding Sites ,Enterococcus hirae ,genetic structures ,Cell-Free System ,Rotation ,Nucleotides ,digestive, oral, and skin physiology ,SciAdv r-articles ,Crystallography, X-Ray ,Microscopy, Atomic Force ,Biochemistry ,Quantitative Biology::Subcellular Processes ,Protein Subunits ,Protein Domains ,Mutation ,Biocatalysis ,Escherichia coli ,Mutant Proteins ,Protein Multimerization ,Protein Structure, Quaternary ,Hydrophobic and Hydrophilic Interactions ,Research Articles ,Research Article - Abstract
The V1-ATPase motor forms metastable asymmetrical structures that suggest the basis for the cooperative transition mechanism., V1-ATPase is an ATP-driven rotary motor that is composed of a ring-shaped A3B3 complex and a central DF shaft. The nucleotide-free A3B3 complex of Enterococcus hirae, composed of three identical A1B1 heterodimers, showed a unique asymmetrical structure, probably due to the strong binding of the N-terminal barrel domain, which forms a crown structure. Here, we mutated the barrel region to weaken the crown, and performed structural analyses using high-speed atomic force microscopy and x-ray crystallography of the mutant A3B3. The nucleotide-free mutant A3B3 complex had a more symmetrical open structure than the wild type. Binding of nucleotides produced a closely packed spiral-like structure with a disrupted crown. These findings suggest that wild-type A3B3 forms a metastable (stressed) asymmetric structure composed of unstable A1B1 conformers due to the strong constraint of the crown. The results further the understanding of the principle of the cooperative transition mechanism of rotary motors.
- Published
- 2018
29. Colorectal Liver Metastasis Resected in a Salvage Operation for Local Recurrence after Proton Beam Radiotherapy
- Author
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Yoshiyuki Nakajima, Ichiro Yamato, Yasuko Tsuji, Satoshi Yasuda, Hiromichi Kanehiro, Shinsaku Obara, Takeo Nomi, Chihiro Kawaguchi, Yukio Aomatsu, and Daisuke Hokuto
- Subjects
Oncology ,medicine.medical_specialty ,Proton ,business.industry ,medicine.medical_treatment ,Gastroenterology ,medicine.disease ,Metastasis ,Radiation therapy ,Internal medicine ,medicine ,Surgery ,Radiology ,business ,Beam (structure) - Published
- 2015
30. Clinical impact of herpesvirus entry mediator expression in human hepatocellular carcinoma
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Ichiro Yamato, Yoshiyuki Nakajima, Daisuke Hokuto, Masayuki Sho, Satoshi Yasuda, Takeo Nomi, and Shinsaku Obara
- Subjects
CD4-Positive T-Lymphocytes ,Male ,Cancer Research ,Herpesvirus entry mediator ,Carcinoma, Hepatocellular ,CD8-Positive T-Lymphocytes ,Biology ,Granzymes ,Interferon-gamma ,Lymphocytes, Tumor-Infiltrating ,Immune system ,medicine ,Humans ,Receptor ,Aged ,Neoplasm Staging ,Perforin ,Liver Neoplasms ,Prognosis ,Acquired immune system ,medicine.disease ,Survival Analysis ,Gene Expression Regulation, Neoplastic ,Granzyme B ,Oncology ,Lymphatic Metastasis ,Hepatocellular carcinoma ,Multivariate Analysis ,Immunology ,biology.protein ,Leukocyte Common Antigens ,Female ,Neoplasm Recurrence, Local ,Receptors, Tumor Necrosis Factor, Member 14 ,CD8 ,Follow-Up Studies - Abstract
Background Herpes virus entry mediator (HVEM), also known as tumour necrosis factor receptor (TNFR) superfamily 14, regulates a variety of physiological and pathological responses in both innate and acquired immunity. Although HVEM is also suggested to be a critical regulator in tumours, actual roles in human cancer are largely unknown. This study aimed to clarify clinical importance of HVEM in human hepatocellular carcinoma (HCC). Patients and methods We studied HVEM expression in 150 HCC patients to explore its clinical relevance, and we examined tumour infiltrating T cells and local immune status of them. Results HVEM was expressed in HCC cells, while no or only limited expression was observed in normal tissues in the liver. Tumour HVEM expression was significantly correlated with age, serum protein induced by vitamin K absence or antagonist-II (PIVKA-II) level, vascular invasion and tumour node metastasis (TNM) stage. Furthermore, tumour HVEM expression significantly correlated with postoperative recurrence and survival. Importantly, multivariate analysis indicated that the HVEM status had an independent prognostic value. Furthermore, HVEM status was inversely correlated with tumour-infiltrating CD4 + , CD8 + and CD45RO + lymphocytes. In addition, it was also associated with reduced expression of perforin, granzyme B and interferon-γ (IFN-γ). Taken together, tumour-expressing HVEM plays a functionally important role in HCC. Conclusion Tumour-expressing HVEM plays a critical role in human HCC, possibly through regulating immune evasion. Therefore, targeting HVEM may be a novel promising therapeutic strategy for HCC.
- Published
- 2015
31. [Long-Term Survival in a Case of Sigmoid Colon Cancer with Multiple Liver Metastases Treated with Repeated Hepatectomies]
- Author
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Yasuyuki, Nakamura, Fumikazu, Koyama, Takeo, Nomi, Ichiro, Yamato, Takeshi, Ueda, Daisuke, Hokutou, Takashi, Inoue, Satoshi, Yasuda, Chihiro, Kawaguchi, Shinsaku, Obara, Takayuki, Nakamoto, Yoshiyuki, Sasaki, Takahiro, Yoshikawa, Hisao, Fujii, and Yoshiyuki, Nakajima
- Subjects
Male ,Organoplatinum Compounds ,Panitumumab ,Liver Neoplasms ,Leucovorin ,Antibodies, Monoclonal ,Sigmoid Neoplasms ,Treatment Outcome ,Antineoplastic Combined Chemotherapy Protocols ,Hepatectomy ,Humans ,Fluorouracil ,Colectomy ,Aged - Abstract
A 75-year-old man was diagnosed with sigmoid colon cancer with multiple liver metastases at our hospital in May 2010. He underwent mFOLFOX6 and panitumumab chemotherapy for 6 months. He then underwent sigmoidectomy, lymphadenectomy D3, partial resection of 2 parts of S6, and cholecystectomy in January 2011. However, he underwent partial resection of the liver an additional 4 times in the 5 years followingthe primary operation. Despite multiple liver metastases, he is alive 5 years after the primary operation, havingsurvived 5 hepatectomies for multiple resectable liver metastases.
- Published
- 2017
32. Eosinophilic cholangitis coexisted with idiopathic thrombocytopenic purpura: Report of a case
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Ichiro Yamato, Kawaguchi Chihiro, Takatsugu Yamada, Satoshi Yasuda, Takeo Nomi, Daisuke Hokuto, Yoshiyuki Nakajima, and Shinsaku Obara
- Subjects
medicine.medical_specialty ,Hepatology ,business.industry ,Bile duct ,medicine.medical_treatment ,Cancer ,respiratory system ,medicine.disease ,Thrombocytopenic purpura ,Gastroenterology ,Primary sclerosing cholangitis ,Infectious Diseases ,medicine.anatomical_structure ,hemic and lymphatic diseases ,Internal medicine ,Prednisolone ,Medicine ,Eosinophilic cholangitis ,Cholecystectomy ,business ,Rare disease ,medicine.drug - Abstract
Eosinophilic cholangitis is a rare disease of which only 31 cases have been reported. Eosinophilic infiltration causes stricture of the bile duct diffusely or locally, and the imaging of eosinophilic cholangitis resembles primary sclerosing cholangitis or cancer of the bile tract. For eosinophilic cholangitis, treatment with steroid is effective and the prognosis is good. Therefore, its accurate diagnosis is very important. Here, we describe a patient with eosinophilic cholangitis who was also diagnosed with idiopathic thrombocytopenic purpura (ITP). He was treated for ITP using prednisolone, the unexpected sudden interruption of which caused severe deterioration of eosinophilic cholangitis and acute cholecystitis. Cholecystectomy and choledochojejunostomy were performed, and the addition of treatment by prednisolone resulted in a good clinical course. This is the first report on eosinophilic cholangitis coexisting with ITP.
- Published
- 2014
33. Ion Selectivity Mechanism of Escherichia Coli OmpF Porin: a Molecular Dynamics Simulation/ free Energy Calculation Study
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Ichiro Yamato, Tadashi Ando, Atsushi Suenaga, and Yasuhiro Matsuura
- Subjects
Molecular dynamics ,Ion selectivity ,Chemical physics ,Chemistry ,Porin ,medicine ,Conductance ,medicine.disease_cause ,Escherichia coli ,Mechanism (sociology) ,Energy (signal processing) - Published
- 2014
34. Energy and information flows in biological systems: Bioenergy transduction of V
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Ichiro, Yamato, Takeshi, Murata, and Andrei, Khrennikov
- Subjects
Adenosine Triphosphatases ,Entropy ,Animals ,Humans ,Quantum Theory - Abstract
We classify research fields in biology with respect to flows of materials, energy, and information. We investigate energy transducing mechanisms in biology, using as a representative the typical molecular rotary motor V
- Published
- 2016
35. Significant involvement of herpesvirus entry mediator in human esophageal squamous cell carcinoma
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Masahiro Ito, Kiyohiko Hotta, Tetsuya Tanaka, Satoshi Yasuda, Yoshiyuki Nakajima, Masayuki Sho, Tomoyoshi Takayama, Noboru Konishi, Keiji Shimada, Kohei Wakatsuki, Ichiro Yamato, Kazuhiro Migita, and Sohei Matsumoto
- Subjects
Cancer Research ,Small interfering RNA ,Herpesvirus entry mediator ,Cell growth ,business.industry ,medicine.medical_treatment ,Cancer ,Immunotherapy ,Esophageal cancer ,medicine.disease ,Oncology ,Tumor progression ,Immunology ,medicine ,Gene silencing ,business - Abstract
BACKGROUND Herpesvirus entry mediator (HVEM) is known to regulate immune response and to be expressed in several human malignancies. However, to the authors's knowledge, the precise role of HVEM in human cancer biology remains unknown. The objective of the current study was to clarify the clinical significance of HVEM in human esophageal squamous cell carcinoma as well as its in vivo functions. METHODS HVEM expression was evaluated in 103 patients with esophageal squamous cell carcinoma to explore its clinical relevance and prognostic value. The functions of HVEM in tumors were analyzed in vitro and in vivo using the small interfering RNA (siRNA) silencing technique. RESULTS HVEM expression was found to be significantly correlated with depth of tumor invasion and lymph node metastasis. Furthermore, it was found to be inversely correlated with tumor-infiltrating CD4+, CD8+, and CD45RO+ lymphocytes. It is important to note that HVEM status was identified as an independent prognostic marker. HVEM gene silencing significantly inhibited cancer cell proliferation in vitro and cancer growth in vivo. This antitumor effect was associated with reduced cell proliferation activity. The effect was also correlated with the induction of CD8+ cells and upregulation of local immune response. CONCLUSIONS HVEM plays a critical role in both tumor progression and the evasion of host antitumor immune responses, possibly through direct and indirect mechanisms. Therefore, HVEM may be a promising therapeutic target for human esophageal cancer. Cancer 2014;120:808–817. © 2013 American Cancer Society.
- Published
- 2013
36. Basic Properties of Rotary Dynamics of the Molecular Motor Enterococcus hirae V1-ATPase
- Author
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Takaho Terada, Yoshiko Ishizuka-Katsura, Hiroyuki Noji, Ichiro Yamato, Yoshihiro Minagawa, Noboru Ohsawa, Hiroshi Ueno, Ryota Iino, Takeshi Murata, Shigeyuki Yokoyama, Eiro Muneyuki, Mayu Hara, and Mikako Shirouzu
- Subjects
Models, Molecular ,Vacuolar Proton-Translocating ATPases ,Stator ,Kinetics ,Thermodynamics ,Bioenergetics ,Crystallography, X-Ray ,Biochemistry ,Michaelis–Menten kinetics ,law.invention ,Adenosine Triphosphate ,Reaction rate constant ,Bacterial Proteins ,law ,Enterococcus hirae ,Molecular motor ,Protein Structure, Quaternary ,Molecular Biology ,biology ,Chemistry ,Thermus thermophilus ,Time constant ,Cell Biology ,biology.organism_classification ,Crystallography ,Enterococcus - Abstract
V-ATPases are rotary molecular motors that generally function as proton pumps. We recently solved the crystal structures of the V1 moiety of Enterococcus hirae V-ATPase (EhV1) and proposed a model for its rotation mechanism. Here, we characterized the rotary dynamics of EhV1 using single-molecule analysis employing a load-free probe. EhV1 rotated in a counterclockwise direction, exhibiting two distinct rotational states, namely clear and unclear, suggesting unstable interactions between the rotor and stator. The clear state was analyzed in detail to obtain kinetic parameters. The rotation rates obeyed Michaelis-Menten kinetics with a maximal rotation rate (Vmax) of 107 revolutions/s and a Michaelis constant (Km) of 154 μm at 26 °C. At all ATP concentrations tested, EhV1 showed only three pauses separated by 120°/turn, and no substeps were resolved, as was the case with Thermus thermophilus V1-ATPase (TtV1). At 10 μm ATP (⪡Km), the distribution of the durations of the ATP-waiting pause fit well with a single-exponential decay function. The second-order binding rate constant for ATP was 2.3 × 106 m−1 s−1. At 40 mm ATP (⪢Km), the distribution of the durations of the catalytic pause was reproduced by a consecutive reaction with two time constants of 2.6 and 0.5 ms. These kinetic parameters were similar to those of TtV1. Our results identify the common properties of rotary catalysis of V1-ATPases that are distinct from those of F1-ATPases and will further our understanding of the general mechanisms of rotary molecular motors.
- Published
- 2013
37. Non-Kolmogorovian Approach to the Context-Dependent Systems Breaking the Classical Probability Law
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Masanori Ohya, Irina Basieva, Andrei Khrennikov, Ichiro Yamato, and Masanari Asano
- Subjects
Open quantum system ,Quantum probability ,Theoretical physics ,Quantum t-design ,Probability amplitude ,Law ,Quantum process ,Quantum operation ,General Physics and Astronomy ,Quantum algorithm ,Quantum information ,Mathematics - Abstract
There exist several phenomena breaking the classical probability laws. The systems related to such phenomena are context-dependent, so that they are adaptive to other systems. In this paper, we present a new mathematical formalism to compute the joint probability distribution for two event-systems by using concepts of the adaptive dynamics and quantum information theory, e.g., quantum channels and liftings. In physics the basic example of the context-dependent phenomena is the famous double-slit experiment. Recently similar examples have been found in biological and psychological sciences. Our approach is an extension of traditional quantum probability theory, and it is general enough to describe aforementioned contextual phenomena outside of quantum physics.
- Published
- 2013
38. A model of epigenetic evolution based on theory of open quantum systems
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Ichiro Yamato, Yoshiharu Tanaka, Irina Basieva, Masanari Asano, Andrei Khrennikov, and Masanori Ohya
- Subjects
business.industry ,Computer science ,Systems biology ,Bioengineering ,Epigenome ,Neo-Darwinism ,symbols.namesake ,Lamarckism ,Master equation ,Operational approach ,symbols ,Epigenetics ,Artificial intelligence ,Statistical physics ,business ,Molecular Biology ,Quantum ,Research Article ,Biotechnology - Abstract
We present a very general model of epigenetic evolution unifying (neo-)Darwinian and (neo-)Lamarckian viewpoints. The evolution is represented in the form of adaptive dynamics given by the quantum(-like) master equation. This equation describes development of the information state of epigenome under the pressure of an environment. We use the formalism of quantum mechanics in the purely operational framework. (Hence, our model has no direct relation to quantum physical processes inside a cell.) Thus our model is about probabilities for observations which can be done on epigenomes and it does not provide a detailed description of cellular processes. Usage of the operational approach provides a possibility to describe by one model all known types of cellular epigenetic inheritance.
- Published
- 2013
39. Simultaneous blockade of programmed death 1 and vascular endothelial growth factor receptor 2 (VEGFR2) induces synergistic anti-tumour effect in vivo
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Hitoshi Yoshiji, Hideo Yagita, Ichiro Yamato, Satoshi Yasuda, Yoshiyuki Nakajima, Kohei Wakatsuki, Masayuki Sho, and Satoshi Nishiwada
- Subjects
Antiangiogenesis ,medicine.drug_class ,Programmed Cell Death 1 Receptor ,Immunology ,Antitumour immunity ,Angiogenesis Inhibitors ,Adenocarcinoma ,Pharmacology ,Biology ,Monoclonal antibody ,Proinflammatory cytokine ,Neovascularization ,Mice ,Lymphocytes, Tumor-Infiltrating ,In vivo ,Cell Line, Tumor ,PD-1 ,medicine ,Animals ,Humans ,Immunology and Allergy ,Mice, Inbred BALB C ,Neovascularization, Pathologic ,Antibodies, Monoclonal ,Drug Synergism ,Kinase insert domain receptor ,Original Articles ,Neoplasms, Experimental ,Vascular Endothelial Growth Factor Receptor-2 ,Immune checkpoint ,Blockade ,VEGFR2 ,Cell culture ,Colonic Neoplasms ,Female ,medicine.symptom - Abstract
Recent basic and clinical studies have shown that the programmed death ligand (PD-L)/PD-1 pathway has a significant role in tumour immunity, and its blockade has a therapeutic potential against several human cancers. We hypothesized that anti-angiogeneic treatment might augment the efficacy of PD-1 blockade. To this end, we evaluated combining the blockade of PD-1 and vascular endothelial growth factor receptor 2 (VEGFR2) in a murine cancer model using Colon-26 adenocarcinoma. Interestingly, simultaneous treatment with anti-PD-1 and anti-VEGFR2 monoclonal antibodies (mAbs) inhibited tumour growth synergistically in vivo without overt toxicity. Blocking VEGFR2 inhibited tumour neovascularization significantly, as demonstrated by the reduced number of microvessels, while PD-1 blockade had no impact on tumour angiogenesis. PD-1 blockade might promote T cell infiltration into tumours and significantly enhanced local immune activation, as shown by the up-regulation of several proinflammatory cytokine expressions. Importantly, VEGFR2 blockade did not interfere with T cell infiltration and immunological activation induced by PD-1 blockade. In conclusion, simultaneous blockade of PD-1 and VEGFR2 induced a synergistic in-vivo anti-tumour effect, possibly through different mechanisms that might not be mutually exclusive. This unique therapeutic strategy may hold significant promise for future clinical application., 博士(医学)・甲第600号・平成25年5月29日, © 2013 British Society for Immunology, This article has been accepted for publication in Clinical and experimental immunology Published by Oxford University Press.
- Published
- 2013
40. Clinical impact of tumor-infiltrating CD45RO+ memory T cells on human gastric cancer
- Author
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Tomoyoshi Takayama, Ichiro Yamato, Sohei Matsumoto, Masahiro Ito, Kohei Wakatsuki, Kazuhiro Migita, Tetsuya Tanaka, Kiyohiko Hotta, Masayuki Sho, and Yoshiyuki Nakajima
- Subjects
Adult ,CD4-Positive T-Lymphocytes ,Male ,Cancer Research ,Pathology ,medicine.medical_specialty ,chemical and pharmacologic phenomena ,complex mixtures ,Disease-Free Survival ,Interferon-gamma ,Lymphocytes, Tumor-Infiltrating ,Stomach Neoplasms ,immune system diseases ,hemic and lymphatic diseases ,Humans ,Medicine ,Interferon gamma ,Aged ,Aged, 80 and over ,Oncogene ,business.industry ,Cancer ,hemic and immune systems ,General Medicine ,Middle Aged ,Prognosis ,medicine.disease ,Acquired immune system ,Immunohistochemistry ,Molecular medicine ,Early Gastric Cancer ,Oncology ,Apoptosis ,Cancer research ,Leukocyte Common Antigens ,Female ,Neoplasm Recurrence, Local ,business ,Immunologic Memory ,medicine.drug - Abstract
Memory T cells survive for months and even years and are critical for host defense in humans. They have been recently suggested to play a significant role in tumor immunity. In this study, we aimed to investigate the clinical impact of tumor-infiltrating memory T cells on human gastric cancer. We evaluated CD45RO(+)T cells infiltrating into primary gastric cancer tissues by immunohistochemistry in 101 patients with gastric cancer. Patients were classified into 2 groups (CD45RO(+Hi) and CD45RO(+Lo)) based on the number of positively stained T cells. There was no significant correlation observed between CD45RO status and post-operative prognosis in early gastric cancer. By contrast, in advanced cancer, the post-operative overall and disease-free survival of patients with CD45RO(+Hi) were significantly improved compared to those of patients with CD45RO(+Lo). In addition, CD45RO status in the primary tumors significantly correlated with the development of post-operative recurrence, particularly peritoneal recurrence. Furthermore, the local expression of interferon-γ (IFN-γ) in the CD45RO(+Hi) tumors was significantly higher than that in the CD45RO(+Lo) tumors, suggesting that CD45RO(+) T cells induced local immune activation. Multivariate analysis indicated that the CD45RO(+) status was an independent prognostic factor in advanced gastric cancer. In conclusion, tumor-infiltrating CD45RO(+) memory T cells are functional and have significant prognostic value in human gastric cancer. Our data suggest that adaptive immune response is clinically critical in gastric cancer.
- Published
- 2013
41. Development of Cell Systems Simulator Using Biochemical Data
- Author
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Seigo Itoh, Tadashi Ando, and Ichiro Yamato
- Subjects
medicine.anatomical_structure ,Chemistry ,Cell ,medicine ,Simulation - Published
- 2013
42. Quantum Adaptivity in Biology: From Genetics to Cognition
- Author
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Masanari Asano, Andrei Khrennikov, Masanori Ohya, Yoshiharu Tanaka, Ichiro Yamato, Masanari Asano, Andrei Khrennikov, Masanori Ohya, Yoshiharu Tanaka, and Ichiro Yamato
- Subjects
- Bioinformatics, Adaptation (Biology)
- Abstract
This book examines information processing performed by bio-systems at all scales: from genomes, cells and proteins to cognitive and even social systems. It introduces a theoretical/conceptual principle based on quantum information and non-Kolmogorov probability theory to explain information processing phenomena in biology as a whole.The book begins with an introduction followed by two chapters devoted to fundamentals, one covering classical and quantum probability, which also contains a brief introduction to quantum formalism, and another on an information approach to molecular biology, genetics and epigenetics. It then goes on to examine adaptive dynamics, including applications to biology, and non-Kolmogorov probability theory.Next, the book discusses the possibility to apply the quantum formalism to model biological evolution, especially at the cellular level: genetic and epigenetic evolutions. It also presents a model of the epigenetic cellular evolution based on the mathematical formalism of open quantum systems. The last two chapters of the book explore foundational problems of quantum mechanics and demonstrate the power of usage of positive operator valued measures (POVMs) in biological science.This book will appeal to a diverse group of readers including experts in biology, cognitive science, decision making, sociology, psychology, and physics; mathematicians working on problems of quantum probability and information and researchers in quantum foundations.
- Published
- 2015
43. Rotation Mechanism of Molecular Motor V
- Author
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Yuta, Isaka, Toru, Ekimoto, Yuichi, Kokabu, Ichiro, Yamato, Takeshi, Murata, and Mitsunori, Ikeguchi
- Subjects
Adenosine Triphosphatases ,Rotation ,Proteins ,Molecular Dynamics Simulation ,Protein Multimerization ,Protein Structure, Quaternary - Abstract
Enterococcus hirae V1-ATPase is a molecular motor composed of the A3B3 hexamer ring and the central stalk. In association with ATP hydrolysis, three catalytic AB pairs in the A3B3 ring undergo conformational changes, which lead to a 120° rotation of the central stalk. To understand how the conformational changes of three catalytic pairs induce the 120° rotation of the central stalk, we performed multiscale molecular dynamics (MD) simulations in which coarse-grained and all-atom MD simulations were combined using a fluctuation matching methodology. During the rotation, a catalytic AB pair spontaneously adopted an intermediate conformation, which was not included in the initial inputs of the simulations and was essentially close to the “bindable-like” structure observed in a recently solved crystal structure. Furthermore, the creation of a space between the bindable-like and tight pairs was required for the central stalk to rotate without steric hindrance. These cooperative rearrangements of the three catalytic pairs are crucial for the rotation of the central stalk.
- Published
- 2016
44. Pharmacokinetics and Histopathological Findings of Chemoembolization Using Cisplatin Powder Mixed with Degradable Starch Microspheres in a Rabbit Liver Tumor Model
- Author
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Masayuki Sho, Toshiko Hirai, Hiroshi Sakaguchi, Toshihiro Tanaka, Chiho Ohbayashi, Masato Takano, Kimihiko Kichikawa, Yasushi Fukuoka, Hideyuki Nishiofuku, Takeshi Sato, Shota Tatsumoto, Nagaaki Marugami, Ichiro Yamato, and Tetsuya Masada
- Subjects
Pathology ,medicine.medical_specialty ,Liver tumor ,Pharmacology ,030218 nuclear medicine & medical imaging ,Microsphere ,03 medical and health sciences ,0302 clinical medicine ,Hepatic Artery ,Liver Neoplasms, Experimental ,Pharmacokinetics ,Medicine ,Animals ,Infusions, Intra-Arterial ,Radiology, Nuclear Medicine and imaging ,Chemoembolization, Therapeutic ,Cisplatin ,Degradable starch microspheres ,Dose-Response Relationship, Drug ,business.industry ,Liver Neoplasms ,Starch ,medicine.disease ,Microspheres ,Drug concentration ,Apoptosis ,030220 oncology & carcinogenesis ,Hepatic arterial flow ,Rabbits ,Powders ,Cardiology and Cardiovascular Medicine ,business ,medicine.drug - Abstract
The purpose of this study is to evaluate the pharmacokinetics and histopathological findings of transarterial chemoembolization (TACE) using cisplatin powder mixed with degradable starch microspheres (DSM) (Cis/DSM-TACE) compared with cisplatin arterial infusion (Cis-AI). Eighteen rabbits with VX2 liver tumors were divided into two groups: Cis/DSM-TACE (n = 9) and Cis-AI (n = 9) groups. In the Cis/DSM-TACE group, a mixture of cisplatin powder and DSM was injected until stasis of hepatic arterial flow was achieved. In the Cis-AI group, cisplatin solution was infused. The platinum concentrations in VX2 tumors in the Cis/DSM-TACE group at 24 and 72 h were significantly elevated compared with those in the Cis-AI group (P = .016 and .019, respectively). There were no significant differences in the platinum concentrations in plasma. Histopathological examination revealed the presence of several microspheres inside the tumors at 1 h, which completely disappeared at 24 h. Tumor cell apoptosis at 1 h in the Cis/DSM-TACE group was more frequently observed compared with that in the Cis-AI group (P = .006). TACE using cisplatin powder mixed with DSM provides a higher drug concentration in tumors, thereby achieving stronger antitumor effects compared with arterial infusion of cisplatin solution.
- Published
- 2016
45. The prognosis of liver resection for patients with four or more colorectal liver metastases has not improved in the era of modern chemotherapy
- Author
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Daisuke, Hokuto, Takeo, Nomi, Ichiro, Yamato, Satoshi, Yasuda, Shinsaku, Obara, Takahiro, Yoshikawa, Chihiro, Kawaguchi, Takatsugu, Yamada, Hiromichi, Kanehiro, and Yoshiyuki, Nakajima
- Subjects
Adult ,Aged, 80 and over ,Male ,Organoplatinum Compounds ,Liver Neoplasms ,Leucovorin ,Antineoplastic Agents ,Adenocarcinoma ,Middle Aged ,Prognosis ,Survival Analysis ,Neoadjuvant Therapy ,Tumor Burden ,Oxaliplatin ,Treatment Outcome ,Chemotherapy, Adjuvant ,Antineoplastic Combined Chemotherapy Protocols ,Hepatectomy ,Humans ,Female ,Fluorouracil ,Colorectal Neoplasms ,Aged ,Follow-Up Studies ,Retrospective Studies - Abstract
The impact of perioperative chemotherapy on patients with multiple colorectal liver metastases (CRLM) remains unclear. We attempted to examine whether the introduction of modern chemotherapies has improved the prognosis of patients that undergo liver resection for ≥4 CRLM.Between January 1990 and December 2013, 194 patients underwent liver resection for CRLM at our institution. The outcomes of the patients with ≥4 and 1-3 CRLM were compared before and after 2005, when modern chemotherapies were introduced to Japan.There were 50 and 144 patients with ≥4 (Group 1) and 1-3 (Group 2) CRLM, respectively. The overall survival (OS) rate of Group 1 was significantly worse than that of Group 2 (P = 0.0007). The OS rate of Group 2 was significantly better after 2005 than before 2004 (P = 0.039), while no such differences were observed in Group 1. Multivariate analysis identified three prognostic factors in Group 1: a serum carcinoembryonic antigen level of ≥20 ng/ml (P = 0.018), a serum cancer antigen 19-9 level of ≥100 U/ml (P = 0.018), and a primary colorectal cancer N factor of ≥N2 (P = 0.023).The prognosis of patients with ≥4 CRLM that undergo liver resection has not improved despite the development of modern chemotherapies. J. Surg. Oncol. 2016;114:959-965. © 2016 Wiley Periodicals, Inc.
- Published
- 2016
46. The Administration of Celecoxib as an Analgesic after Liver Resection Is Safe
- Author
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Satoshi Yasuda, Ichiro Yamato, Takahiro Yoshikawa, Takatsugu Yamada, Shinsaku Obara, Hiromichi Kanehiro, Takeo Nomi, Yoshiyuki Nakajima, Chihiro Kawaguchi, and Daisuke Hokuto
- Subjects
Adult ,Male ,medicine.medical_specialty ,Gastrointestinal bleeding ,Adolescent ,Analgesic ,030230 surgery ,Postoperative Hemorrhage ,03 medical and health sciences ,chemistry.chemical_compound ,Young Adult ,0302 clinical medicine ,Medicine ,Hepatectomy ,Humans ,Aged ,Retrospective Studies ,Aged, 80 and over ,Venous Thrombosis ,Creatinine ,Analgesics ,Pain, Postoperative ,business.industry ,Portal Vein ,Incidence (epidemiology) ,Incidence ,Gastroenterology ,Retrospective cohort study ,Acute Kidney Injury ,Length of Stay ,Middle Aged ,medicine.disease ,Surgery ,Portal vein thrombosis ,chemistry ,Celecoxib ,030220 oncology & carcinogenesis ,Anesthesia ,Female ,business ,Gastrointestinal Hemorrhage ,Indocyanine green ,medicine.drug - Abstract
Background: There are a few studies that have evaluated postoperative analgesia. The aim of this study was to evaluate the safety of administering celecoxib to manage postoperative pain after liver surgery. Methods: The cases of patients who underwent liver resection at Nara Medical University from April 2008 to December 2015 were retrospectively analyzed. From January 2013 to December 2015, celecoxib was routinely administered (600 mg/day on postoperative day (POD) 2 and 400 mg/day from POD 3-7), whereas celecoxib was not administered from April 2008 to December 2012. The patients' baseline characteristics, the operative procedures, and postoperative complications were analyzed. Results: In total, 207 patients were administered celecoxib (celecoxib group), whereas 246 were not (non-celecoxib group). The preoperative serum total bilirubin and creatinine levels and indocyanine green retention rate at 15 min values of the 2 groups were similar. Similar incidences of overall and major complications (Clavien-Dindo classification ≥grade IIIa) were seen in both groups (33.8 vs. 36.2%, p = 0.601 and 12.1 vs. 12.6%, p = 0.866, respectively). No significant differences in the incidences of gastrointestinal bleeding, acute renal failure, or portal vein thrombosis were observed between the groups. Conclusions: The use of celecoxib for postoperative analgesia in the early period after liver resection is safe.
- Published
- 2016
47. Three-body system metaphor for the two-slit experiment and Escherichia coli lactose-glucose metabolism
- Author
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Yoshiharu Tanaka, Ichiro Yamato, Andrei Khrennikov, Masanari Asano, and Masanori Ohya
- Subjects
0301 basic medicine ,030103 biophysics ,General Mathematics ,General Physics and Astronomy ,Lactose ,Carbohydrate metabolism ,medicine.disease_cause ,01 natural sciences ,Models, Biological ,010305 fluids & plasmas ,03 medical and health sciences ,chemistry.chemical_compound ,0103 physical sciences ,medicine ,Escherichia coli ,Body system ,Physics ,Models, Statistical ,General Engineering ,Articles ,Glucose ,chemistry ,Quantum interference ,Metaphor ,Double-slit experiment ,Quantum Theory ,Biological system - Abstract
We compare the contextual probabilistic structures of the seminal two-slit experiment (quantum interference experiment), the system of three interacting bodies and Escherichia coli lactose–glucose metabolism. We show that they have the same non-Kolmogorov probabilistic structure resulting from multi-contextuality. There are plenty of statistical data with non-Kolmogorov features; in particular, the probabilistic behaviour of neither quantum nor biological systems can be described classically. Biological systems (even cells and proteins) are macroscopic systems and one may try to present a more detailed model of interactions in such systems that lead to quantum-like probabilistic behaviour. The system of interactions between three bodies is one of the simplest metaphoric examples for such interactions. By proceeding further in this way (by playing with n -body systems) we shall be able to find metaphoric mechanical models for complex bio-interactions, e.g. signalling between cells, leading to non-Kolmogorov probabilistic data.
- Published
- 2016
48. PCA-1/ALKBH3 Contributes to Pancreatic Cancer by Supporting Apoptotic Resistance and Angiogenesis
- Author
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Keiji Shimada, Yuko Ueda, Kiyohiko Hotta, Ichiro Yamato, Satoshi Yasuda, Yoshiyuki Nakajima, Naoko Shigi, Noboru Konishi, Masayuki Sho, and Kazutake Tsujikawa
- Subjects
Adult ,Male ,Cancer Research ,Pathology ,medicine.medical_specialty ,DNA repair ,Angiogenesis ,Blotting, Western ,Apoptosis ,Mice, SCID ,Biology ,Transfection ,Dioxygenases ,Mice ,Antigens, Neoplasm ,In vivo ,Pancreatic cancer ,Biomarkers, Tumor ,medicine ,Animals ,Humans ,Gene silencing ,RNA, Small Interfering ,Aged ,Aged, 80 and over ,Neovascularization, Pathologic ,Reverse Transcriptase Polymerase Chain Reaction ,Cancer ,Middle Aged ,medicine.disease ,Immunohistochemistry ,Xenograft Model Antitumor Assays ,Pancreatic Neoplasms ,DNA Repair Enzymes ,Oncology ,Tissue Array Analysis ,Cancer research ,Female ,AlkB Homolog 3, Alpha-Ketoglutarate-Dependent Dioxygenase - Abstract
The PCA-1/ALKBH3 gene implicated in DNA repair is expressed in several human malignancies but its precise contributions to cancer remain mainly unknown. In this study, we have determined its functions and clinical importance in pancreatic cancer. PCA-1/ALKBH3 functions in proliferation, apoptosis and angiogenesis were evaluated in human pancreatic cancer cells in vitro and in vivo. Further, PCA-1/ALKBH3 expression in 116 patients with pancreatic cancer was evaluated by immunohistochemistry. siRNA-mediated silencing of PCA-1/ALKBH3 expression induced apoptosis and suppressed cell proliferation. Conversely, overexpression of PCA-1/ALKBH3 increased anchorage-independent growth and invasiveness. In addition, PCA-1/ALKBH3 silencing downregulated VEGF expression and inhibited angiogenesis in vivo. Furthermore, immunohistochemical analysis showed that PCA-1/ALKBH3 expression was abundant in pancreatic cancer tissues, where it correlated with advanced tumor status, pathological stage and VEGF intensity. Importantly, patients with low positivity of PCA-1/ALKBH3 expression had improved postoperative prognosis compared with those with high positivity. Our results establish PCA-1/ALKBH3 as important gene in pancreatic cancer with potential utility as a therapeutic target in this fatal disease. Cancer Res; 72(18); 4829–39. ©2012 AACR.
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- 2012
49. Pathological and clinical impact of neoadjuvant chemoradiotherapy using full-dose gemcitabine and concurrent radiation for resectable pancreatic cancer
- Author
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Satoshi Yasuda, Hideyuki Nishiofuku, Nagaaki Marugami, Toshihiro Tanaka, Takeo Nomi, Ichiro Yamato, Masayuki Sho, Takahiko Kasai, Kimihiko Kichikawa, Takahiro Akahori, Yasunori Enomonoto, Daisuke Hokuto, Yoshiyuki Nakajima, Shoichi Kinoshita, Tetsuro Tamamoto, Chihiro Kawaguchi, and Masatoshi Hasegawa
- Subjects
Adult ,Male ,medicine.medical_specialty ,medicine.medical_treatment ,Deoxycytidine ,Pancreatectomy ,Pancreatic cancer ,Ribonucleotide Reductases ,medicine ,Humans ,Pancreas ,Neoadjuvant therapy ,Aged ,Retrospective Studies ,Aged, 80 and over ,Dose-Response Relationship, Drug ,Hepatology ,business.industry ,Dose-Response Relationship, Radiation ,Chemoradiotherapy ,Perioperative ,Middle Aged ,medicine.disease ,Magnetic Resonance Imaging ,Gemcitabine ,Neoadjuvant Therapy ,Surgery ,Pancreatic Neoplasms ,Regimen ,Treatment Outcome ,Pancreatic fistula ,Female ,Tomography, X-Ray Computed ,business ,Immunosuppressive Agents ,Follow-Up Studies ,medicine.drug - Abstract
The therapeutic options available as preoperative strategies for resectable pancreatic cancer have received worldwide attention. We have recently introduced neoadjuvant chemoradiotherapy (NACRT) to achieve local control and possibly complete cure. In this study, we have retrospectively evaluated its impact on pathology and the perioperative clinical course in addition to its safety. Sixty-one patients who received full-dose gemcitabine (1000 mg/m2) preoperatively with concurrent radiation (50 or 54 Gy) were evaluated. Seventy-one patients who received no preoperative therapy served as controls. Perioperative outcomes, postoperative complications, immunonutritional status, and the performance of adjuvant chemotherapy were compared. Fifty-nine patients (97 %) completed NACRT. Toxicity was acceptable and the regimen was feasible as outpatient treatment. The perioperative outcomes were closely comparable to control. The rate of pancreatic fistula was lower and hospital stay was shorter in the NACRT group. The rate of lymph node metastasis and stage was lower in the NACRT group. Furthermore, R0 resection could be achieved in 92 % of patients treated with NACRT. Nutritional status decreased after NACRT and further deteriorated during adjuvant chemotherapy. The initiation of postoperative chemotherapy was delayed in the NACRT group. Our current protocol of neoadjuvant chemoradiotherapy is feasible and substantially improves the pathology. However, it has some detrimental effects on postoperative nutritional status and performance of adjuvant chemotherapy. Furthermore, it should be noted that there is a possibility of arterial complications.
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- 2012
50. Calculating the Na+ translocating V-ATPase catalytic site affinity for substrate binding by homology modeled NtpA monomer using molecular dynamics/free energy calculation
- Author
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Zahed Muhammed, Takeshi Murata, Ichiro Yamato, Satoshi Arai, Atsushi Suenaga, and Shinya Saijo
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Protein subunit ,Adenylyl Imidodiphosphate ,Molecular Sequence Data ,Thermodynamic integration ,Molecular Dynamics Simulation ,chemistry.chemical_compound ,Molecular dynamics ,Sequence Analysis, Protein ,Enterococcus hirae ,Catalytic Domain ,Materials Chemistry ,Nucleotide ,Amino Acid Sequence ,Physical and Theoretical Chemistry ,Cation Transport Proteins ,Spectroscopy ,Adenosine Triphosphatases ,chemistry.chemical_classification ,biology ,biology.organism_classification ,Computer Graphics and Computer-Aided Design ,Crystallography ,Monomer ,Membrane ,chemistry ,Thermodynamics ,Homology (chemistry) ,Enterococcus - Abstract
Vacuolar ATPase (V-ATPase) of Enterococcus hirae is composed of a soluble catalytic domain (V₁; NtpA₃-B₃-D-G) and an integral membrane domain (V₀; NtpI-K₁₀) connected by a central and two peripheral stalks (NtpC, NtpD-G and NtpE-F). Recently nucleotide binding of catalytic NtpA monomer has been reported (Arai et al.). In the present study, we calculated the nucleotide binding affinity of NtpA by molecular dynamics (MD) simulation/free energy calculation using MM-GBSA approach based on homology modeled structure of NtpA monomer docked with ATP analogue, adenosine 5'-[β, γ-imido] triphosphate (AMP-PNP). The calculated binding free energies showed qualitatively good agreement with experimental data. The calculation was cross-validated further by the rigorous method, thermodynamic integration (TI) simulation. Finally, the interaction between NtpA and nucleotides at the atomic level was investigated by the analyses of components of free energy and the optimized model structures obtained from MD simulations, suggesting that electrostatic contribution is responsible for the difference in nucleotide binding to NtpA monomer. This is the first observation and suggestion to explain the difference of nucleotide binding properties in V-ATPase NtpA subunit, and our method can be a valuable primary step to predict nucleotide binding affinity to other subunits (NtpAB, NtpA₃B₃) and to explore subunit interactions and eventually may help to understand energy transduction mechanism of E. hirae V-ATPase.
- Published
- 2012
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