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Patients with early recurrence of hepatocellular carcinoma have poor prognosis

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Hepatobiliary & Pancreatic Diseases International 2017年第3期16卷 279-288页

作者： Tomoki Kobayashi Hiroshi Aikata Tsuyoshi Kobayashi hideki Ohdan Koji Arihiro Kazuaki Chayama Department of Gastroenterology and Metabolism Hiroshima University Hospital Hiroshima Japan Department of Anatomical Pathology Hiroshima University Hospital Hiroshima Japan Department of Gastroenterological and Transplant Surgery Applied Life Sciences Institute of Biomedical and Health Sciences Hiroshima University Hiroshima Japan Liver Research Project Center Hiroshima University Hiroshima Japan

BACKGROUND： Early recurrence （ER） after hepatic resection （HR） is a poor prognostic factor for patients with hepatocellular carcinoma （HCC）. This study aimed to identify the clinico- pathological features, outcomes, and risk factors for ER after HR for small HCC in order to clarify the reasons why ER is a worse recurrence pattern. METHODS： We retrospectively examined 130 patients who underwent HR for small HCC （___30 mm）. Recurrence was clas- sifted into ER （〈2 years） and late recurrence （LR）（_〉2 years）. The clinicopathological features, outcomes, and risk factors for ER were analyzed by multivariate analysis. RESULTS： ER was observed in 39 patients （30.0%）. The sur- vival rate of the ER group was significantly lower than that of the LR group （P〈0.005）, and ER was an independent prognos- tic factor for poor survival （P=0.0001）. The ER group had a significantly higher frequency （P=0.0039） and shorter interval （P=0.027） of development to carcinoma beyond the Milan criteria （DBMC） compared with the LR group, and ER was an independent risk factor for DBMC （P〈0.0001）. Multi-nodularity, non-simple nodular type, and microvascular invasion were independent predictors for ER （P=0.012, 0.010, and 0.019, respectively）.CONCLUSIONS： ER was a highly malignant recurrence pattern associated with DBMC and subsequent poor survival after HR for small HCC. Multi-nodularity, non-simple nodular type, and microvascular invasion predict ER, and taking these factors into consideration may be useful for the decision of the treatment strategy for small HCC after HR.

关键词： early recurrence small hepatocellular carcinoma risk factors beyond the Milan criteria

Design and evaluation of an extended-release matrix tablet formulation; the combination of hypromellose acetate succinate and hydroxypropylcellulose

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Asian Journal of Pharmaceutical Sciences 2017年第2期12卷 149-156页

作者： Sachiko Fukui hideki Yano Shuichi Yada Tsuyoshi Mikkaichi Hidemi Minami Formulation Technology Research Laboratories Daiichi Sankyo Co.Ltd.1-2-58HiromachiShinagawa-kuTokyo 140-8710Japan Drug Metabolism&Pharmacokinetics Research Laboratories Daiichi Sankyo Co.Ltd.1-2-58HiromachiShinagawa-kuTokyo 140-8710Japan

The purpose of this study was to develop an extended-release(ER) matrix tablet that shows robust dissolution properties able to account for the variability of pH and mechanical stress in the GI tract using a combination of enteric polymer and hydrophilic polymer. Hypromellose acetate succinate(HPMCAS) and hydroxypropylcellulose(HPC) were selected as ER polymers for the ER matrix tablet(HPMCAS/HPC ER matrix tablet). Oxycodone hydrochloride was employed as a model drug. Dissolution properties of the HPMCAS/HPC ER matrix tablets were evaluated and were not affected by the pH of the test medium or paddle rotating *** a USP apparatus 3(bio-relevant dissolution method), dissolution profiles of the HPMCAS/HPC ER matrix tablets containing oxycodone hydrochloride were similar to that of the reference product(OxyC ontin). Moreover, in vivo performance after oral administration of the HPMCAS/HPC ER matrix tablets to humans was simulated by GastroP lus based on dissolution profiles from the USP apparatus 3. The plasma concentration-time profile simulated was similar to that of the reference product. These results suggest that the combination of HPMCAS and HPC shows a robust dissolution profile against pH and paddle rotating speed and indicates the appropriate extended-release profile in humans.

关键词： Extended-release matrix tablet Hypromellose acetate succinate Hydroxypropylcellulose Robust dissolution USP apparatus 3

Primary hepatic leiomyosarcoma with liver metastasis of rectal cancer

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World Journal of Gastroenterology 2012年第38期18卷 5479-5484页

作者： Kiyoto Takehara hideki Aoki Yuko Takehara Rie Yamasaki Kohji Tanakaya Hitoshi Takeuchi Department of Gastroenterological Surgery Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences Okayama 700-8558 Japan Department of Surgery National Hospital Organization Iwakuni Clinical Center Yamaguchi 740-8510 Japan Department of Clinical Examination National Hospital Organization Iwakuni Clinical Center Yamaguchi 740-8510 Japan

Primary hepatic leiomyosarcoma is a particularly rare tumor with a poor prognosis. Curative resection is currently the only effective treatment, and the efficacy of chemotherapy is unclear. This represents the first case report of a patient with primary hepatic leiomyosarcoma co-existing with metastatic liver carcinoma. We present a 59-year-old man who was diagnosed preoperatively with rectal cancer with multiple liver metastases. He underwent a curative hepatectomy after a series of chemotherapy regimens with modified FOLFOX6 consisting of 5-fluorouracil, leucovorin and oxaliplatin plus bevacizumab, FOLFIRI consisting of 5-fluorouracil, leucovorin and irinotecan plus bevacizumab, and irinotecan plus cetuximab. One of the liver tumors showed a different response to chemotherapy and was diag-nosed as a leiomyosarcoma following histopathological examination. This case suggests that irinotecan has the potential to inhibit the growth of hepatic leiomyosarcomas. The possibility of comorbid different histological types of tumors should be suspected when considering the treatment of multiple liver tumors.

关键词： Leiomyosarcoma Rectal cancer Metastasis Chemotherapy Surgery

Application of highwall mining system in weak geological condition

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International Journal of Coal Science & Technology 2016年第3期3卷 311-321页

作者： Takashi Sasaoka Tri Karian Akihiro Hamanaka hideki Shimada Kikuo Matsui Department of Earth Resources Engineering KyushuUniversity Fukuoka 819-0395 Japan

Almost all the coal is produced from open cut mines in Indonesia. As a consequence of open cut mine application, a great deal of coal is left out in the highwalls of the mined-out pits. Highwall mining systems can be used to recover this coal. The use of highwall mining systems has increasingly come into play in the US and Australia. However, it is not common in Indonesia. Moreover, Indonesia coal measure is categorized as weak geological condition. Some problems are likely to arise during the application of the highwall mining system for example instability of openings and highwalls due to the roof and pillar failures. Therefore, study of highwall mining system application in Indonesia is needed in order to increase the recovery rate of coal mining in Indonesia. This paper described the characteristics of the highwa!l mining system and discussed the appropriate highwall mining system application in weak geological condition, Indonesia. From the results of a series of laboratory tests and numerical analyses, it can be concluded that the stability of pillars and mine openings in auger mining systems is much higher than that in CHM and an auger mining system is suitable for such as very weak/poor strata conditions. Moreover, the application of backfilling system is very effective for improvement of the stability of pillar and openings.

关键词： Open cut mine Left out coal Highwall mining systems Weak geological condition

Hepatic reconstruction from fetal porcine liver cells using a radial flow bioreactor

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World Journal of Gastroenterology 2008年第17期14卷 2740-2747页

作者： Yuji Ishii Ryota Saito hideki Marushima Ryusuke Ito Taro Sakamoto Katsuhiko Yanaga Department of Surgery the Jikei University School of Medicine

AIM： To examine the efficacy of the radial flow bioreactor （RFB） as an extracorporeal bioartificial liver （BAL） and the reconstruction of liver organoids using embryonic pig liver cells. METHODS： We reconstructed the liver organoids using embryonic porcine liver cells in the RFB. We also determined the gestational time window for the optimum growth of embryonic porcine liver cells. Five weeks of gestation was designated as embryonic day （E） 35 and 8 wk of gestation was designated as E56. These cells were cultured for one week before morphological and functional examinations. Moreover, the efficacy of pulsed adminisbation of a high concentration hepatocyte growth factor （HGF） was examined. RESULTS： Both cell growth and function were excellent after harvesting on E35. The pulsed administration of a high concentration of HGF promoted the differentiation and maturation of these fetal hepatic cells. Microscopic examination of organoids in the RFB revealed palisading and showed that bile duct-like structures were well developed, indicating that the organoids were mini livers. Transmission electron microscopy revealed microvilli on the luminal surfaces of bile duct-like structures and junctional complexes, which form the basis of the cytoskeleton of epithelial tissues. Furthermore, strong expression of connexin （Cx） 32, which is the main protein of hepatocyte gap junctions, was observed. With respect to liver function, ammonia detoxification and urea synthesis were shown to be performed effectively. CONCLUSION： Our system can potentially be applied in the fields of BAL and transplantation medicine.

关键词： Liver organoid Radial flow bioreactor Bioartificial liver Fetal porcine liver Hepatocyte growthfactor

A candidate targeting molecule of insulin-like growth factor-Ⅰ receptor for gastrointestinal cancers

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World Journal of Gastroenterology 2010年第46期16卷 5779-5789页

作者： Yasushi Adachi Hiroyuki Yamamoto Hirokazu Ohashi Takao Endo David P Carbone Kohzoh imai Yasuhisa Shinomura First Department of Internal Medicine Sapporo Medical University Department of Internal Medicine Sapporo Shirakabadai Hospital Vanderbilt-Ingram Cancer Center and Departments of Medicine and Cell Biology Vanderbilt University

Advances in molecular research in cancer have brought new therapeutic strategies into clinical *** new group of targets is tyrosine kinase receptors,which can be treated by several strategies,including small molecule tyrosine kinase inhibitors(TKIs) and monoclonal antibodies(mAbs).Aberrant activation of growth factors/receptors and their signal pathways are required for malignant transformation and progression in gastrointestinal(GI) *** concept of targeting specif ic carcinogenic receptors has been validated by successful clinical application of many new *** I insulin-like growth factor(IGF) receptor(IGF-IR) signaling potently stimulates tumor progression and cellular differentiation,and is a promising new molecular target in human *** this review,we focus on this promising therapeutic target,*** IGF/IGF-IR axis is an important modifier of tumor cell proliferation,survival,growth,and treatment sensitivity in many malignant diseases,including human GI *** studies demonstrated that downregulation of IGF-IR signals reversed the neoplastic phenotype and sensitized cells to anticancer *** results were mainly obtained through our strategy of adenoviruses expressing dominant negative IGF-IR(IGF-IR/dn) against gastrointestinal cancers,including esophagus,stomach,colon,and *** also summarize a variety of strategies to interrupt the IGFs/IGF-IR axis and their preclinical *** mAbs and TKIs targeting IGF-IR have entered clinical trials,and early results have suggested that these agents have generally acceptable safety profiles as single *** summarize the advantages and disadvantages of each strategy and discuss the merits/demerits of dual targeting of IGF-IR and other growth factor receptors,including Her2 and the insulin receptor,as well as other alternatives and possible drug ***,IGF-IR might be a candidate for a molecular therapeutic target in human GI carcino

关键词： Dominant negative Gastrointestinal cancer Insulin like growth factor-I receptor Monoclonal anti-body Tyrosine kinase inhibitor

Niche Differentiation of Phenol-Degrading Microorganisms in UASB Granular Sludge as Revealed by Fluorescence in situ Hybridization

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Engineering 2022年第2期8卷 61-66页

作者： Kengo Kubota Kei Igarashi Masayoshi Yamada Yasuyuki Takemura Yu-You Li hideki Harada Department of Civil and Environmental Engineering Tohoku UniversitySendai 980-8579Japan Department of Urban Environmental Design and Engineering National Institute of TechnologyKagoshima CollegeKirishima 899-5193Japan New Industry Creation Hatchery Center Tohoku UniversitySendai 980-8579Japan

A microbial community structure of granules harvested from an anaerobic sludge blanket reactor treating phenolic wastewater was investigated using fluorescence in situ hybridization(FISH)and clone library *** of Syntrophorhabdaceae and Cryptanaerobacter were observed to be responsible for phenol *** accurate taxonomic assignment of Cryptanaerobacter clones,phylogenetic analysis using nearly full-length 16S ribosomal RNA(rRNA)gene sequences was *** oligonucleotide probes were designed to detect the following three taxonomic groups:Syntrophorhabdaceae,Cryptanaerobacter,and *** analysis of thin sections of anaerobic granules showed a random distribution of bacteria and ***,a well-defined distribution of Syntrophorhabdaceae,Cryptanaerobacter,and Syntrophus was *** and Syntrophus were found on the outer layer of the granules and were closely associated with each other,while Syntrophorhabdaceae was located in the deeper part of the *** specific distribution of the bacteria is most likely due to their metabolic association and affinity for the *** degradation in the granular sludge was observed to be carried out in the following ***,Cryptanaerobacter converts phenol to benzoate,which is then degraded by Syntrophus into *** syntrophic degradation of phenol occurs near the surface of the granule,where the phenol concen-tration is *** the deeper part of the granule,where the phenol concentration is lower,Syntrophorhabdaceae degrades phenol into *** observed that Syntrophorhabdaceae is less likely to produce benzoate as an intermediate to feed the neighboring organisms,which contradicts the theo-ries presented by previous studies.

关键词： Cryptanaerobacter Fluorescence in situ hybridization Anaerobic phenol degradation Syntrophorhabdaceae Syntrophus UASB granular sludge

Time effect and prediction of broken rock bulking coefficient on the base of particle discrete element method

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International Journal of Mining Science and Technology 2021年第4期31卷 643-651页

作者： Fanfei Meng Hai Pu Takashi Sasaoka hideki Shimada Sifei Liu Tumelo KM Dintwe Ziheng Sha Department of Earth Resources Engineering Faculty of EngineeringKyushu UniversityFukuoka 819-0395Japan State Key Laboratory for Geomechanics&Deep Underground Engineering China University of Mining and TechnologyXuzhou 221116China College of Mining Engineering and Geology Xinjiang Institute of EngineeringUrumqi 830023China

Bulking characteristics of gangue are of great significance for the stability of goafs in mining overburden in the caving *** this paper,a particle discrete element method with clusters to represent gangue was adopted to explore the bulking coefficient time effect of the broken rock in the caving zone under three-dimensional triaxial compression *** phenomena of stress corrosion,deformation,and failure of rock blocks were simulated in the numerical ***,a new criterion of rock fragments damage was put *** was found that the broken rock has obvious viscoelastic properties.A new equation based on the Burgers creep model was proposed to predict the bulking coefficient of broken rock.A deformation characteristic parameter of the prediction equation was analyzed,which can be set as a fixed value in the mid-and long-term prediction of the bulking *** are quadratic function relationships between the deformation characteristic parameter value and Talbot gradation index,axial pressure and confining pressure.

关键词： Bulking coefficient Time effect Deformation prediction Broken rock Particle discrete element model

In Vivo Investigation of Zr-Based Bulk Metallic Glasses Sub-Periosteally Implanted on the Bone Surface

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Journal of Materials Science and Chemical Engineering 2016年第1期4卷 46-51页

作者： Kazuhiro imai Department of Life Sciences Graduate School of Arts and Sciences The University of Tokyo Tokyo Japan

Bulk metallic glasses (BMG) show higher strength and lower Young’s modulus than SUS 316L stainless steel and Ti-6Al-4V alloys. This study aimed to investigate the reaction of Zr-based BMG sub-periosteally implanted on the surface of the rat femur, thereby evaluate the possibility of the BMG as biomaterials for osteosynthetic devices. Zr65Al7.5Ni10Cu17.5 BMG ribbons with 10 mm length, 2 mm width and 0.5 mm thickness were implanted sub-periosteally on the femur surface in three male Wistar rats for 6 weeks. Systemic effects were evaluated by measuring Cu and Ni levels in the blood, and local effects were evaluated by the histological observation of the surrounding soft tissues in contact with the BMG. The reaction of the surface of the BMG was examined with scanning electron microscopy. No increase of Cu and Ni levels in the blood was recognized. In the scanning electron microscopy observation, spherical deposits which were considered as sodium chloride crystals were observed. Neither breakage nor pitting corrosion was noted. BMG will be a promising metallic biomaterial for osteosynthetic device that must be removed.

关键词： Amorphous Alloy Bulk Metallic Glasses Biomaterial Osteosynthetic Device