193 results on '"Masamichi Mizuma"'
Search Results
152. Japan Pancreatic Cancer Registry of Japan Pancreas Society: Comparison between the conventional database and National Clinical Database (NCD)
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Masamichi Mizuma, Hiraku Kumamaru, Sohei Satoi, Shin Hamada, Hiroyuki Konno, Yasuyuki Seto, Tooru Shimosegawa, Shinichi Egawa, Hisato Igarashi, Yuzo Kodama, Hiroaki Miyata, Michiaki Unno, Kazuhiro Mizumoto, and Takao Itoi
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medicine.medical_specialty ,Hepatology ,business.industry ,Endocrinology, Diabetes and Metabolism ,General surgery ,Gastroenterology ,medicine.disease ,03 medical and health sciences ,0302 clinical medicine ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,Internal medicine ,Pancreatic cancer ,medicine ,030211 gastroenterology & hepatology ,Pancreas ,business - Published
- 2016
153. Outcomes after total pancreatectomy in elderly patients
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Naoaki Sakata, Takanori Morikawa, Kunihiro Masuda, Michiaki Unno, Masamichi Mizuma, Hiroki Hayashi, Tatsuyuki Takadate, Hideo Ohtsuka, Masaharu Ishida, Fuyuhiko Motoi, Kei Nakagawa, Takeshi Naitoh, Shimpei Maeda, Kyohei Ariake, Koji Fukase, Shinichi Egawa, and Takeshi Aoki
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medicine.medical_specialty ,Hepatology ,business.industry ,Total pancreatectomy ,Endocrinology, Diabetes and Metabolism ,General surgery ,Gastroenterology ,Medicine ,business - Published
- 2016
154. A retrospective study of four cases undergoing total remnant pancreatectomy for metachronous double pancreatic ductal adenocarcinoma
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Tatsuyuki Takadate, Fuyuhiko Motoi, Kyohei Ariake, Takanori Morikawa, Shimpei Maeda, Shinichi Egawa, Takashi Naitoh, Takeshi Aoki, Kunihiro Masuda, Kei Nakagawa, Naoaki Sakata, Koji Fukase, Hideo Ohtsuka, Masaharu Ishida, Michiaki Unno, Masamichi Mizuma, and Hiroki Hayashi
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medicine.medical_specialty ,Pancreatic ductal adenocarcinoma ,Hepatology ,business.industry ,Endocrinology, Diabetes and Metabolism ,General surgery ,medicine.medical_treatment ,Pancreatectomy ,Gastroenterology ,Medicine ,Retrospective cohort study ,Radiology ,business - Published
- 2016
155. Risk factors of peritoneal recurrence after pancreatectomy suggested the possibility of intraoperative dissemination of cancer cells
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Tatsuyuki Takadate, Shimpei Maeda, Takanori Morikawa, Kei Nakagawa, Masamichi Mizuma, Hiroki Hayashi, Kunihiro Masuda, Hideo Ohtsuka, Shinichi Egawa, Kyohei Ariake, Takeshi Naitoh, Michiaki Unno, Fuyuhiko Motoi, and Koji Fukase
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medicine.medical_specialty ,Hepatology ,business.industry ,Endocrinology, Diabetes and Metabolism ,medicine.medical_treatment ,General surgery ,Pancreatectomy ,Cancer cell ,Gastroenterology ,Medicine ,business - Published
- 2016
156. Neoadjuvant chemotherapy with gemcitabine and S1 (NAC-GS) for borderline resectable pancreatic cancer
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Kei Nakagawa, Takanori Morikawa, Koji Fukase, Shimpei Maeda, Michiaki Unno, Masamichi Mizuma, Hiroki Hayashi, Naoaki Sakata, Fuyuhiko Motoi, Kyohei Ariake, Kunihiro Masuda, Hideo Ohtsuka, Masaharu Ishida, and Tatsuyuki Takadate
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Oncology ,medicine.medical_specialty ,Chemotherapy ,Hepatology ,business.industry ,Endocrinology, Diabetes and Metabolism ,medicine.medical_treatment ,Gastroenterology ,medicine.disease ,Gemcitabine ,Borderline resectable ,Pancreatic cancer ,Internal medicine ,medicine ,business ,medicine.drug - Published
- 2016
157. Sa1451 Phase II Study of Intravenous and Intraperitoneal Paclitaxel With S-1 for Pancreatic Ductal Adenocarcinoma Patients With Peritoneal Metastasis
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Goro Honda, Masamichi Mizuma, Tomohisa Yamamoto, Michiaki Unno, Fuyuhiko Motoi, Hironori Ishigami, Hiroaki Yanagimoto, Masanao Kurata, Hiroyuki Isayama, Tsutomu Fujii, A-Hon Kwon, Naminatsu Takahara, Sohei Satoi, and Suguru Yamada
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Oncology ,medicine.medical_specialty ,Peritoneal metastasis ,Pancreatic ductal adenocarcinoma ,Hepatology ,business.industry ,Gastroenterology ,Phases of clinical research ,chemistry.chemical_compound ,Paclitaxel ,chemistry ,Internal medicine ,Medicine ,business - Published
- 2016
158. Feasibility assessment of gemcitabine combined with S-1 as neo-adjuvant chemotherapy (NAC-GS) for pancreatic cancer in elderly patients
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Takanori Morikawa, Kunihiro Masuda, Fuyuhiko Motoi, Ryo Okada, Takeshi Aoki, Sumiko Maeda, Michiaki Unno, Hideki Hayashi, Takeshi Naitoh, Masamichi Mizuma, Kei Kawaguchi, Kei Nakagawa, Kyouhei Ariake, Koji Fukase, Hideo Ohtsuka, Masaharu Ishida, and Natsumi Sakata
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Oncology ,medicine.medical_specialty ,Hepatology ,business.industry ,Endocrinology, Diabetes and Metabolism ,Gastroenterology ,medicine.disease ,Gemcitabine ,Pancreatic cancer ,Internal medicine ,medicine ,Neo adjuvant chemotherapy ,business ,medicine.drug - Published
- 2016
159. Presented at the 64th Annual Scientific Meeting of the Japanese Association for thoracic surgery: wet-lab training for thoracic surgery at the laboratory animal facilities
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Yoshinori Okada, Masafumi Noda, Takashi Kondo, Chiaki Endo, Yasushi Hoshikawa, Akira Sakurada, Sumiko Maeda, Masamichi Mizuma, Michiaki Unno, and Noriyuki Kasai
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Pulmonary and Respiratory Medicine ,Suturing techniques ,medicine.medical_specialty ,Swine ,medicine.medical_treatment ,education ,Animals, Laboratory ,medicine ,Surgical skills ,Intubation ,Animals ,Humans ,Fellowships and Scholarships ,Surgical approach ,Venipuncture ,business.industry ,General surgery ,Significant difference ,Suture Techniques ,Internship and Residency ,Thoracic Surgery ,General Medicine ,Surgery ,Cardiothoracic surgery ,Models, Animal ,Clinical Competence ,Cardiology and Cardiovascular Medicine ,Training program ,business - Abstract
The purpose of this study was to describe the animal thoracic training program for the thoracic surgery at the laboratory animal facilities The training was provided for 78 surgical students under the direction of thoracic medical specialists. Students attended lectures and then performed venipuncture, injection, intubation, tracheostomy, surgical cut-down, and thoracic and abdominal surgical approaches. We estimated the detailed surgical skills in two groups (67 residents and 11 thoracic fellows). All students demonstrated satisfactory impressions after training. We found significant difference between the skills of residents and fellows with regard to the haemostasis and suturing techniques. Wet-lab training for thoracic surgery at the laboratory animal facilities is useful for surgical residents and thoracic fellows.
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- 2012
160. Lymph Nodes Metastasis is a Risk Factor for Bone Metastasis From Extrahepatic Cholangiocarcinoma
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Yu Katayose, Tohru Onogawa, Shinichi Egawa, Toshiki Rikiyama, Michiaki Unno, Hiroshi Yoshida, Kei Nakagawa, Hideo Ohtsuka, Kuniharu Yamamoto, Fuyuhiko Motoi, Koji Fukase, Masamichi Mizuma, and Hiroki Hayashi
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Male ,Oncology ,medicine.medical_specialty ,Time Factors ,Lymphovascular invasion ,Perineural invasion ,Bone Neoplasms ,Lymph node metastasis ,Multimodal Imaging ,Risk Assessment ,Metastasis ,Cholangiocarcinoma ,Japan ,Bile Ducts, Extrahepatic ,Predictive Value of Tests ,Risk Factors ,Internal medicine ,Humans ,Medicine ,Neoplasm Invasiveness ,Risk factor ,Aged ,Chi-Square Distribution ,Hepatology ,business.industry ,Gastroenterology ,Bone metastasis ,General Medicine ,Middle Aged ,Prognosis ,medicine.disease ,Survival Analysis ,medicine.anatomical_structure ,Bile Duct Neoplasms ,Lymphatic Metastasis ,Positron-Emission Tomography ,Female ,Lymph Nodes ,Lymph ,Tomography, X-Ray Computed ,business ,Blood vessel - Abstract
BACKGROUND/AIMS The rate and site of bone metastasis from cholangiocarcinoma as well as the prognosis are unclear. Therefore, we intend to make a comparative review of the background to bone metastasis, examine a high-risk group for bone metastasis and use the data towards the improvement in quality of life. METHODOLOGY We studied 200 cases of cholangiocarcinoma resected in our division from January 2003 to April 2010. RESULTS Bone metastasis was confirmed in four cases (2.0%). The survival period after the diagnosis of bone metastasis ranged from 2.9 months to 21.6 months and the average was 6.7 months. We studied histopathological findings of bone metastasis, lymph node metastasis, lymphatic invasion, blood vessel invasion and perineural invasion (ly, v and pn) and found that all of four bone metastasis cases were positive for lymph node metastasis which was a statistically significant factor affecting bone metastasis. CONCLUSIONS Since the number of cases we studied is small, it is difficult to determine whether lymph node metastasis is a risk factor for bone metastasis; however, we think it is necessary to take the probability of bone metastasis into consideration when we provide medical care to patients positive for lymph node metastasis.
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- 2012
161. [A case of distal cholangiocarcinoma with high sensitivity to neoadjuvant chemoradiation therapy]
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Yoichi, Haji, Masamichi, Mizuma, Hiroki, Hayashi, Kei, Nakagawa, Takaho, Okada, Hideo, Otsuka, Shigeru, Ottomo, Naoaki, Sakata, Koji, Fukase, Hiroshi, Yoshida, Tohru, Onogawa, Fuyuhiko, Motoi, Takeshi, Naito, Toshiki, Rikiyama, Yu, Katayose, Shinichi, Egawa, and Michiaki, Unno
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Cholangiocarcinoma ,Male ,Bile Ducts, Intrahepatic ,Bile Duct Neoplasms ,Humans ,Neoplasm Invasiveness ,Chemoradiotherapy ,Middle Aged ,Tomography, X-Ray Computed ,Neoadjuvant Therapy - Abstract
We hypothesized that neoadjuvant chemoradiation therapy for cholangiocarcinoma (NACRAC) using gemcitabine would improve the prognosis of resected cases. Phase II trial of NACRAC is ongoing. We report a very effective case to NACRAC for distal cholangiocarcinoma, which markedly reduced the size and levels of the tumor markers. The patient was a 50- year-old man who presented jaundice. Serum tumor markers were clearly elevated, and abdominal CT scan revealed an enhanced mass in the lower bile duct, a dilatation of the intrahepatic to the middle bile duct and a swollen regional lymph node. After NACRAC, the tumor markers were decreased within a normal range. Also on CT scan, the main tumor was slightly detectable and the swollen node was reduced more than 30% in short diameter. Therefore, the effect of NACRAC was considered PR in RECIST guidelines (ver.1 .1). Pancreaticoduodenectomy was performed 2 weeks after NACRAC. No perioperative complications occurred. Pathological examination showed a good response, Grade 2b on Oboshi-Shimosato's classification. In this case, NACRAC had a good effect in imaging and pathological findings as well as in the tumor markers. Therefore, the neoadjuvant chemoradiation therapy has a potential to improve the prognosis for cholangiocarcinoma.
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- 2011
162. A polymeric nanoparticle formulation of curcumin (NanoCurc™) ameliorates CCl4-induced hepatic injury and fibrosis through reduction of pro-inflammatory cytokines and stellate cell activation
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Balmiki Ray, Haibo Bai, Ming Zhao, Toby C. Cornish, Robert A. Anders, Mehtab Khan, Anirban Maitra, Masamichi Mizuma, Debomoy K. Lahiri, Mena Bekhit, Michelle A. Rudek, Savita Bisht, and Amarnath Maitra
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Male ,Cirrhosis ,Curcumin ,Biological Availability ,Pharmacology ,Chronic liver disease ,Article ,Pathology and Forensic Medicine ,Proinflammatory cytokine ,chemistry.chemical_compound ,Mice ,Fibrosis ,medicine ,Animals ,Molecular Biology ,Cell Line, Transformed ,Liver injury ,Carbon Tetrachloride Poisoning ,Reverse Transcriptase Polymerase Chain Reaction ,Cell Biology ,medicine.disease ,Mice, Inbred C57BL ,chemistry ,Apoptosis ,Immunology ,Hepatic stellate cell ,Nanoparticles ,Inflammation Mediators - Abstract
Plant-derived polyphenols such as curcumin hold promise as a therapeutic agent in the treatment of chronic liver diseases. However, its development is plagued by poor aqueous solubility resulting in poor bioavailability. To circumvent the suboptimal bioavailability of free curcumin, we have developed a polymeric nanoparticle formulation of curcumin (NanoCurc™) that overcomes this major pitfall of the free compound. In this study, we show that NanoCurc™ results in sustained intrahepatic curcumin levels that can be found in both hepatocytes and non-parenchymal cells. NanoCurc™ markedly inhibits carbon tetrachloride-induced liver injury, production of pro-inflammatory cytokines and fibrosis. It also enhances antioxidant levels in the liver and inhibits pro-fibrogenic transcripts associated with activated myofibroblasts. Finally, we show that NanoCurc™ directly induces stellate cell apoptosis in vitro. Our results suggest that NanoCurc™ might be an effective therapy for patients with chronic liver disease.
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- 2011
163. Tyrosine 23 phosphorylation-dependent cell-surface localization of annexin A2 is required for invasion and metastases of pancreatic cancer
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Lanqing Huang, Robert A. Anders, Lei Zheng, Jennifer E. Van Eyk, Dung T. Le, Rajni Sharma, Ashley Leubner, Masamichi Mizuma, Barish H. Edil, Peter B. Illei, Kelly Olino, Elizabeth M. Jaffee, Anirban Maitra, Guanglan Mo, Daniel A. Laheru, and Kelly Foley
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health care facilities, manpower, and services ,Cell ,Cancer Treatment ,lcsh:Medicine ,Metastasis ,Small hairpin RNA ,Mice ,0302 clinical medicine ,Cell Movement ,Basic Cancer Research ,Tumor Cells, Cultured ,Tyrosine ,Neoplasm Metastasis ,Phosphorylation ,lcsh:Science ,Annexin A2 ,0303 health sciences ,Gene knockdown ,Multidisciplinary ,Antibodies, Monoclonal ,3. Good health ,medicine.anatomical_structure ,Oncology ,Liver ,030220 oncology & carcinogenesis ,Medicine ,Female ,RNA Interference ,Cancer Prevention ,Research Article ,congenital, hereditary, and neonatal diseases and abnormalities ,Epithelial-Mesenchymal Transition ,Blotting, Western ,education ,Biology ,Cancer Vaccines ,Disease-Free Survival ,03 medical and health sciences ,Pancreatic Cancer ,Antibody Therapy ,Antigens, Neoplasm ,Pancreatic cancer ,Cell Line, Tumor ,health services administration ,Gastrointestinal Tumors ,medicine ,Biomarkers, Tumor ,Animals ,Humans ,Neoplasm Invasiveness ,Epithelial–mesenchymal transition ,030304 developmental biology ,Cell Membrane ,lcsh:R ,Cancers and Neoplasms ,Neoplasms, Experimental ,medicine.disease ,Molecular biology ,Mice, Inbred C57BL ,Pancreatic Neoplasms ,Cancer research ,lcsh:Q - Abstract
The aggressiveness of pancreatic ductal adenocarcinoma (PDA) is characterized by its high metastatic potential and lack of effective therapies, which is the result of a lack of understanding of the mechanisms involved in promoting PDA metastases. We identified Annexin A2 (ANXA2), a member of the Annexin family of calcium-dependent phospholipid binding proteins, as a new molecule that promotes PDA invasion and metastases. We found ANXA2 to be a PDA-associated antigen recognized by post-treatment sera of patients who demonstrated prolonged survival following treatment with a PDA-specific vaccine. Cell surface ANXA2 increases with PDA development and progression. Knockdown of ANXA2 expression by RNA interference or blocking with anti-ANXA2 antibodies inhibits in vitro invasion of PDA cells. In addition, post-vaccination patient sera inhibits in vitro invasion of PDA cells, suggesting that therapeutic anti-ANXA2 antibodies are induced by the vaccine. Furthermore, cell-surface localization of ANXA2 is tyrosine 23 phosphorylation-dependent; and tyrosine 23 phosphorylation is required for PDA invasion. We demonstrated that tyrosine 23 phosphorylation resulting in surface expression of ANXA2 is required for TGFβ-induced, Rho-mediated epithelial-mesenchymal transition (EMT), linking the cellular function of ANXA2 which was previously shown to be associated with small GTPase-regulated cytoskeletal rearrangements, to the EMT process in PDA. Finally, using mouse PDA models, we showed that shRNA knock-down of ANXA2, a mutation at tyrosine 23, or anti-ANXA2 antibodies, inhibit PDA metastases and prolong mouse survival. Thus, ANXA2 is part of a novel molecular pathway underlying PDA metastases and a new target for development of PDA therapeutics.
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- 2011
164. Corrigendum to 'Activation of Notch1 promotes development of human CD8+ single positive T cells in humanized mice' [Biochem. Biophys. Res. Commun. 447 (2014) 346–351]
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Yoichi Haji, Masamichi Mizuma, Naoto Ishii, Katsuto Hozumi, Kunihiko Moriya, Makiko Suzuki, Takanori So, and Michiaki Unno
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Chemistry ,Biophysics ,Cell Biology ,Molecular Biology ,Biochemistry ,Molecular biology ,CD8 - Published
- 2014
165. Systemic administration of polymeric nanoparticle-encapsulated curcumin (NanoCurc™) blocks tumor growth and metastases in preclinical models of pancreatic cancer
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Dipankar Pramanik, Seung-Mo Hong, Amarnath Maitra, Savita Bisht, Venugopal Chenna, Anirban Maitra, Rajni Sharma, Michael Goggins, Georg Feldmann, Rajani Ravi, Masamichi Mizuma, Collins Karikari, Niki A. Ottenhof, and Michelle A. Rudek
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Cancer Research ,Curcumin ,Polymers ,Biological Availability ,Down-Regulation ,Pharmacology ,Deoxycytidine ,Article ,chemistry.chemical_compound ,Mice ,Subcutaneous Tissue ,In vivo ,Pancreatic cancer ,Cell Line, Tumor ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Animals ,Humans ,Cyclin D1 ,Neoplasm Metastasis ,Cell Proliferation ,business.industry ,NF-kappa B ,Cancer ,Drug Synergism ,medicine.disease ,Primary tumor ,Xenograft Model Antitumor Assays ,Gemcitabine ,Bioavailability ,Pancreatic Neoplasms ,Disease Models, Animal ,Oncology ,chemistry ,Matrix Metalloproteinase 9 ,Systemic administration ,Nanoparticles ,business ,medicine.drug - Abstract
Curcumin or diferuloylmethane is a yellow polyphenol extracted from the rhizome of turmeric (Curcuma longa). A large volume (several hundreds) of published reports has established the anticancer and chemopreventative properties of curcumin in preclinical models of every known major cancer type. Nevertheless, the clinical translation of curcumin has been significantly hampered due to its poor systemic bioavailability, which mandates that patients consume up to 8 to 10 g of the free drug orally each day to achieve detectable levels in circulation. We have engineered a polymeric nanoparticle encapsulated curcumin formulation (NanoCurc) that shows remarkably higher systemic bioavailability in plasma and tissues compared with free curcumin upon parenteral administration. In xenograft models of human pancreatic cancer established in athymic mice, administration of parenteral NanoCurc significantly inhibits primary tumor growth in both subcutaneous and orthotopic settings. The combination of parenteral NanoCurc with gemcitabine results in enhanced tumor growth inhibition versus either single agent, suggesting an additive therapeutic influence in vivo. Furthermore, this combination completely abrogates systemic metastases in orthotopic pancreatic cancer xenograft models. Tumor growth inhibition is accompanied by significant reduction in activation of nuclear factor-κB, as well as significant reduction in expression of matrix metalloproteinase-9 and cyclin D1, in xenografts treated with NanoCurc and gemcitabine. NanoCurc is a promising new formulation that is able to overcome a major impediment for the clinical translation of curcumin to cancer patients by improving systemic bioavailability, and by extension, therapeutic efficacy. Mol Cancer Ther; 9(8); 2255–64. ©2010 AACR.
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- 2010
166. Tumor targeting and imaging in live animals with functionalized semiconductor quantum rods
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Ken-Tye Yong, Anirban Maitra, Rui Hu, Paras N. Prasad, Indrajit Roy, Masamichi Mizuma, Lisa A. Vathy, Hong Ding, and Earl J. Bergey
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Materials science ,Integrin ,Transplantation, Heterologous ,Mice, Nude ,Peptide ,Conjugated system ,Sulfides ,Peptides, Cyclic ,Article ,Mice ,Microscopy, Electron, Transmission ,In vivo ,Pancreatic cancer ,Materials Testing ,Quantum Dots ,medicine ,Cadmium Compounds ,Animals ,Nanotechnology ,General Materials Science ,Whole Body Imaging ,Cytotoxicity ,Selenium Compounds ,Micelles ,chemistry.chemical_classification ,Bioconjugation ,biology ,medicine.disease ,Molecular biology ,Pancreatic Neoplasms ,Spectrometry, Fluorescence ,chemistry ,Zinc Compounds ,Biophysics ,biology.protein ,Female ,Preclinical imaging ,Neoplasm Transplantation - Abstract
In this contribution, we demonstrate that highly luminescent CdSe/CdS/ZnS quantum rods (QRs) coated with PEGylated phospholipids and conjugated with cyclic RGD peptide can be successfully used for tumor targeting and imaging in live animals. The design of these targeted luminescent probes involves encapsulation of hydrophobic CdSe/CdS/ZnS QRs with PEGylated phospholipids, followed by conjugation of these PEGylated phospholipids to ligands that specifically target the tumor vasculature. In vivo optical imaging studies in nude mice bearing pancreatic cancer xenografts, both subcutaneous and orthotopic, indicate that the QR probes accumulate at tumor sites via the cyclic RGD peptides on the QR surface binding to the alpha(V)beta(3) integrins overexpressed in the tumor vasculature, following systemic injection. In vivo tumor detection studies showed no adverse effects even at a dose roughly 6.5 times higher than has been reported for in vivo imaging studies using quantum dots. Cytotoxicity studies indicated the absence of any toxic effect in the cellular and tissue levels arising from functionalized QRs. These results demonstrate the vast potential of QRs as bright, photostable, and biocompatible luminescent probes for the early diagnosis of cancer.
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- 2010
167. Overexpression of adenovirus-mediated p27kip1 lacking the Jab1-binding region enhances cytotoxicity and inhibits xenografted human cholangiocarcinoma growth
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Satoru, Shiraso, Yu, Katayose, Kuniharu, Yamamoto, Masamichi, Mizuma, Shinichi, Yabuuchi, Akira, Oda, Toshiki, Rikiyama, Tohru, Onogawa, Hiroshi, Yoshida, Hiroki, Hayashi, Hideo, Ohtsuka, Fuyuhiko, Motoi, Shinichi, Egawa, Junya, Kato, and Michiaki, Unno
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Cell Nucleus ,COP9 Signalosome Complex ,Blotting, Western ,Cell Cycle ,Intracellular Signaling Peptides and Proteins ,Fluorescent Antibody Technique ,Apoptosis ,Genetic Therapy ,Mice, SCID ,Xenograft Model Antitumor Assays ,Adenoviridae ,Cholangiocarcinoma ,Mice ,Bile Ducts, Intrahepatic ,Bile Duct Neoplasms ,In Situ Nick-End Labeling ,Animals ,Humans ,Female ,Cyclin-Dependent Kinase Inhibitor p27 ,Peptide Hydrolases ,Protein Binding - Abstract
The cyclin-dependent kinase inhibitor (CDK1) p27(kip1) is a negative regulator of cell cycling and has antitumor effects. In our previous study, the recombinant adenovirus expressing wild-type p27(kip1) (Adp27-wt) induced cell cycle arrest and apoptosis, and proved that p27 is a tumor suppressor gene like p53. Another adenovirus vector expressing mutant p27(kip1) (Adp27-mt), which inhibited degradation by the ubiquitin-proteasome system, showed increased protein stability and caused a stronger induction of apoptosis. Recently, the p27(kip1) protein binding with Jab1 (Jun activating binding protein 1) was found to translocate from the nucleus into the cytosol, and then become degraded by the 26S proteasome system. The inhibition of nuclear-cytoplasmic translocation increases the protein stability of p27(kip1) and p27(kip1) with a deletion of the Jab1-binding region (p27-jab-d) is not translocated and not degraded. Therefore, a new recombinant adenovirus (Adp27-jab-d) expressing p27-jab-d was made which was able to induce greater cytotoxicity. Adp27-jab-d inhibited the growth of human cholangiocarcinoma cell line (TFK-1) cells in vitro at 3.3 times (IC(50)) lower concentration than Adp27-wt. Moreover, in a xenografted severe combined immuno-deficient (SCID) mouse model injected with TFK-1 cells in the subcutaneous tissue, treatment by intratumor injection of Adp27-jab-d once a day for 3 days after the tumor was established, inhibited tumor growth more strongly than Adp27-wt or Adp27-mt and even induced tumor regression. However, the flow cytometric TUNEL assay showed little enhancement of apoptosis. Adp27-jab-d was thought to induce not only apoptosis but also necrosis, which was due to a specific effect of the Adp27-jab-d. Thus, by enhancing the cytotoxicity through inhibiting the translocaton of p27(kip1), p27(kip1) lacking the Jab1-binding region might be useful for cancer therapy. The control protein localization might also be a new target not only for cancer treatment, but also other diseases.
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- 2009
168. ZD1839 (IRESSA) stabilizes p27Kip1 and enhances radiosensitivity in cholangiocarcinoma cell lines
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Shinichi, Yabuuchi, Yu, Katayose, Akira, Oda, Masamichi, Mizuma, Satoru, Shirasou, Tsuyoshi, Sasaki, Kuniharu, Yamamoto, Masaya, Oikawa, Toshiki, Rikiyama, Tohru, Onogawa, Hiroshi, Yoshida, Hideo, Ohtuska, Fuyuhiko, Motoi, Shinichi, Egawa, and Michiaki, Unno
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Base Sequence ,X-Rays ,Blotting, Western ,Cell Cycle ,Molecular Sequence Data ,Intracellular Signaling Peptides and Proteins ,Antineoplastic Agents ,Apoptosis ,Gefitinib ,Combined Modality Therapy ,Polymerase Chain Reaction ,Radiation Tolerance ,Cholangiocarcinoma ,ErbB Receptors ,Bile Ducts, Intrahepatic ,Bile Duct Neoplasms ,Mutation ,Quinazolines ,Tumor Cells, Cultured ,Humans ,Cyclin-Dependent Kinase Inhibitor p27 ,Cell Proliferation - Abstract
The prognosis of cholangiocarcinoma patients is extremely poor despite the aggressive multidisciplinary cancer therapies that have been used clinically (1). Recently, molecular target therapy has attracted attention. Epidermal growth factor receptor (EGFR) tyrosine kinase (TK) is a promising target for anticancer therapy. ZD1839 (IRESSA) is an orally active, selective inhibitor of EGFR-TK. This study examined the effects of ZD1839 in TFK-1 and HuCCT1, the human cholangiocarcinoma cell lines that express EGFR. Somatic mutations in the TK domain of the EGFR gene are associated with the sensitivity of lung cancers to ZD1839 (2). In the analysis of the EGFR sequence, no mutations were found in TFK-1 and HuCCT1. The TFK-1 and HuCCT1 cells showed almost the same sensitivity to ZD1839. It is shown that ZD1839 induced apoptotic cell death of TFK-1 cells as indicated by apoptotic morphological changes and an enhancement of TUNEL-positive cells. ZD1839 produced a dose-dependent inhibition of cellular proliferation in TFK-1. Cell cycle analysis demonstrated that ZD1839 induces G1 arrest. Moreover, concurrent evaluation of the expression of p27(Kip1) protein and Jun activating domain-binding protein 1 (Jab1) with ZD1839 by Western blotting analysis was performed. It was found that ZD1839 activity causes an increase of p27(Kip1) stability that correlates with Jab1 down-regulation. Thus, ZD1839 affects key cellular pathways, controlling cell proliferation and apoptosis. Furthermore, the treatment of TFK-1 with ZD1839 reduced the cell survival after radiation exposure. ZD1839 in combination with radiation produced a dose-dependent and synergic inhibitory effect on cellular proliferation. In conclusion, these results suggest that ZD1839 may have clinical activity against cholangiocarcinoma.
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- 2009
169. Up-regulated p27Kip1 reduces matrix metalloproteinase-9 and inhibits invasion of human breast cancer cells
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Masamichi, Mizuma, Yu, Katayose, Kuniharu, Yamamoto, Satoru, Shiraso, Tsuyoshi, Sasaki, Shinichi, Yabuuchi, Akira, Oda, Kunihiro, Masuda, Toshiki, Rikiyama, Tohru, Onogawa, Hideo, Ohtsuka, Fuyuhiko, Motoi, Shinichi, Egawa, and Michiaki, Unno
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Reverse Transcriptase Polymerase Chain Reaction ,Cell Cycle ,Intracellular Signaling Peptides and Proteins ,Breast Neoplasms ,Cell Growth Processes ,Transfection ,Retinoblastoma Protein ,Up-Regulation ,Matrix Metalloproteinase 9 ,Cell Line, Tumor ,Humans ,Neoplasm Invasiveness ,RNA, Messenger ,Cyclin-Dependent Kinase Inhibitor p27 - Abstract
p27Kip1 is a cyclin-dependent kinase inhibitor which has been reported to be associated with invasion, metastasis and angiogenesis in malignant tumors, but its mechanism of action remains unknown. Here, it was examined whether p27Kip1 has an inhibitory effect on cancer cell invasion and correlates with matrix metalloproteinase expression (MMPs).The human breast cancer cell line MDA-MB-231 and MDA-MB-231 transfectedp27Kip1 MDA-MB-p27 were used for the invasion assay, Western blotting and real-time quantitative RT-PCR.In the invasion assay, the invasion of MDA-MB-p27 was significantly less than that of the parent cell line. In Western blotting analyses, the protein level of MMP-9 was also reduced in MDA-MB-p27. Furthermore, the activity of MMP-9 in cell culture supernatants was lower in MDA-MB-p27 as compared with enzyme-linked immunosorbent assays. In real-time quantitative RT-PCR, the mRNA level of MMP-9 was lower in MDA-MB-p27 cells.Up-regulation of p27Kip1 remarkably inhibited the invasion of the breast cancer cells, in part due to the reduced expression of MMP-9. This is the first report of p27Kip1 modulating MMP-9 and indicating that p27Kip1 might play a key role in tumor cell invasion.
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- 2008
170. 2088 Clinical features and management of anorectal cancer in Crohn's disease: Japanese single centre study
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Shinobu Ohnuma, Hideki Hayashi, M. Nagao, Kei Nakagawa, Takanori Morikawa, N. Tanaka, M. Kobayashi, Kimiko Watanabe, Hideaki Karasawa, Taku Aoki, N. Sakata, H. Imoto, T. Tsuchiya, T. Abe, Masamichi Mizuma, Fuyuhiko Motoi, Michiaki Unno, Takeshi Naitoh, K. Kudo, and H. Musha
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Cancer Research ,medicine.medical_specialty ,Crohn's disease ,Single centre ,Oncology ,business.industry ,General surgery ,Internal medicine ,Anorectal cancer ,Medicine ,business ,medicine.disease ,Gastroenterology - Published
- 2015
171. Neoadjuvant chemoradiation therapy for cholangiocarcinoma to improve R0 resection rate: The first report of phase II study
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Takaho Okada, Kunihiro Masuda, Michiaki Unno, Kei Kawaguchi, Fuyuhiko Motoi, Ryo Okada, Takeshi Naitoh, Masamichi Mizuma, Shinichi Yabuuchi, Hiroki Hayashi, Hiroshi Yoshida, Hideo Ohtsuka, Masaharu Ishida, Naoaki Sakata, Takeshi Aoki, Kei Nakagawa, Koji Fukase, Takanori Morikawa, and Yu Katayose
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Cancer Research ,medicine.medical_specialty ,Oncology ,Hepatic lobectomy ,business.industry ,Medicine ,Phases of clinical research ,business ,R0 resection ,Surgery - Abstract
402 Background: With the much-improved surgical techniques of hepatic lobectomy, but the long-term survival of patients undergoing such surgery remains far from satisfactory. Then, to improve the prognosis of cholangiocarcinoma patients, we have applied neoadjuvant chemoradiation therapy followed by conventional resection for possibly resectable cholangiocarcinoma, named NACRAC. Here, we analyzed and evaluated the Phase II (P-2) study. Methods: Patients with histologically or cytologically confirmed adenocarcinoma of the extra- and hilar cholangiocarcinoma were enrolled from 2008 to 2013 at Department Surgery, Tohoku University Hospital. The dose of gemcitabine was determined 600mg/m2 of gemcitabine with external beam radiation therapy (1.8-Gy daily fractions to a total dose of 45 Gy) ( Hepatogastroenterology. 2011;58(112):1866-72.). The primary endpoint of P-2 is R0-resection rate. We hypothesized that R0-resection rate become from 60% to 80%. Results: Total numbers of enrolled patients were 25 cases. 22 cases were operated, and 20 cases were resected. After chemoradiation, 3 cases were not operated by liver metastases, tumor progression, and heart failure. 2 cases were not resected by peritoneal carcinomatosis. One case was diagnosed as pancreatic cancer at the final pathological diagnosis. R0-resectinn cases were 17 cases. R0 resection rate was 89.6% (17/19) among operated cases. In recruited 24 cases (A pancreatic cancer was not included), R0 resection rate was 70.8% (17/24). Grade 3 and 4 adverse events (AE) were neutropenia, leukocytopenia, and Thrombocytopenia. No grade 5 AE and no fatal AE in this P-2 study. Conclusions: Neoadjuvant chemoradiation therapy with conventional resections appears to be effective and well tolerated. After both disease free survival and overall survival are going to be fixed, we will decide a proper indication of neoadjuvant therapy for cholangiocarcinoma. Trial Registration: UMIN Clinical Trials Registry (UMIN-CTR) UMIN UMIN000000992 and UMIN000001754 Clinical trial information: 000001754.
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- 2015
172. Adenovirus expressing mutant p27kip1 enhanced apoptosis and inhibited the growth of xenografted human breast cancer
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Kuniharu Yamamoto, Masanori Suzuki, Satoru Shiraso, Choon Taek Lee, Tsuyoshi Sasaki, Yu Katayose, Michiaki Unno, Shinichi Yabuuchi, Akira Oda, Toru Onogawa, Masaya Oikawa, Masamichi Mizuma, and Toshiki Rikiyama
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Mutant ,Blotting, Western ,Genetic Vectors ,Apoptosis ,Breast Neoplasms ,Mice, SCID ,medicine.disease_cause ,Adenoviridae ,Mice ,Breast cancer ,Surgical oncology ,Cell Line, Tumor ,In Situ Nick-End Labeling ,Medicine ,Animals ,Humans ,Immunoprecipitation ,Mutation ,business.industry ,Cell Cycle ,Cancer ,General Medicine ,DNA, Neoplasm ,Neoplasms, Experimental ,medicine.disease ,Molecular biology ,Gene Expression Regulation, Neoplastic ,Surgery ,Female ,business ,Human breast ,Cyclin-Dependent Kinase Inhibitor p27 ,Neoplasm Transplantation - Abstract
To evaluate the anti-tumor effects of a novel adenovirus expressing mutant p27(kip1) (Adp27-mt), which consists of a mutation of Thr-187/Pro-188 to Met-187/Ile-188.Using the human breast cancer cell lines, MDA-MB-231, ZR-75-1, and MCF-7, we tested Adp27-mt for cell cycle assay, growth inhibition assay, and TdT-mediated dUTP-biotin nick end labeling in a human breast cancer-grafted severe combined immunodeficiency (SCID) mouse model.The mutant p27(kip1) induced stronger apoptosis in the breast cancer cell lines than adenovirus expressing wild-type p27(kip1) (Adp27-wt). Adp27-mt inhibits cell growth significantly; being about 5- and 3.5-fold stronger for IC50 than Adp27-wt in the breast cancer cell lines, MDA-MD-231 and ZR-75-1, respectively. In the human breast cancer-grafted SCID mouse model, Adp27-mt induced tumor regression and antitumor effects significantly better than Adp27-wt. Furthermore, Adp27-mt mainly caused G2/M arrest in the cell cycle progression, whereas Adp27-wt mediated a G1/S arrest 48 h after infection.The mutant p27(kip1) protein induced apoptosis, and inhibited cell growth more efficiently with stronger anti-tumor effects than wild-type p27(kip1). Thus, the recombinant adenovirus expressing mutant p27(kip1) could be useful in gene therapy against breast cancer.
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- 2006
173. Multicenter Phase II Study of Intravenous and Intraperitoneal Paclitaxel With S-1 for Pancreatic Ductal Adenocarcinoma Patients With Peritoneal Metastasis.
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Sohei Satoi, Tsutomu Fujii, Hiroaki Yanagimoto, Fuyuhiko Motoi, Masanao Kurata, Naminatsu Takahara, Suguru Yamada, Tomohisa Yamamoto, Masamichi Mizuma, Goro Honda, Hiroyuki Isayama, Michiaki Unno, Yasuhiro Kodera, Hironori Ishigami, and Masanori Kon
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Objective: To evaluate the clinical efficacy and tolerability of intravenous (i.v.) and intraperitoneal (i.p.) paclitaxel combined with S-l, "an oral fluoropyrimidine derivative containing tegafur, gimestat, and otastat potassium'' in chemotherapy-naive pancreatic ductal adenocarcinoma (PDAC) patients with peritoneal metastasis. Background: PDAC patients with peritoneal metastasis (peritoneal deposits and/or positive peritoneal cytology) have an extremely poor prognosis. An effective treatment strategy remains elusive. Methods: Paclitaxel was administered i.v. at 50mg/m² and i.p. at 20mg/m² on days 1 and 8. S-1 was administered at 80 mg/m²/d for 14 consecutive days, followed by 7 days of rest. The primary endpoint was 1-year overall survival (OS) rate. The secondary endpoints were antitumor effect and safety (UMIN000009446). Results: Thirty-three patients who were pathologically diagnosed with the presence of peritoneal dissemination (n = 22) and/or positive peritoneal cytology (n = 11) without other organ metastasis were enrolled. The tumor was located at the pancreatic head in 7 patients and the body/tail in 26 patients. The median survival time was 16.3 (11.47-22.57) months, and the 1-year survival rate was 62%. The response rate and disease control rate in assessable patients were 36% and 82%, respectively. OS in 8 patients who underwent conversion surgery was significantly higher than that of nonsurgical patients (n = 25, P = 0.0062). Grade 3/4 hematologic toxicities occurred in 42% of the patients and nonhematologic adverse events in 18%. One patient died of thrombosis in the superior mesenteric artery. Conclusions: This regimen has shown promising clinical efficacy with acceptable tolerability in chemotherapy-naive PDAC patients with peritoneal metastasis. [ABSTRACT FROM AUTHOR]
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- 2017
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174. Aberrant activation of Notch signaling in extrahepatic cholangiocarcinoma: clinicopathological features and therapeutic potential for cancer stem cell-like properties.
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Shuichi Aoki, Masamichi Mizuma, Yayoi Takahashi, Yoichi Haji, Ryo Okada, Tomoya Abe, Hideaki Karasawa, Keiichi Tamai, Takaho Okada, Takanori Morikawa, Hiroki Hayashi, Kei Nakagawa, Fuyuhiko Motoi, Takeshi Naitoh, Yu Katayose, and Michiaki Unno
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NOTCH proteins , *CELLULAR signal transduction , *LIVER cancer , *CHOLANGIOCARCINOMA , *CANCER stem cells , *THERAPEUTICS - Abstract
Background: Little is known about the roles of Notch signaling in cholangiocarcinoma (CC). The expression of hairy and enhancer of split 1 (Hes-1) has not been investigated yet in resected specimens of CC. Notch signaling has been reported to be related to cancer stem cell (CSC) like properties in some malignancies. Our aim is to investigate the participation of Notch signaling in resected specimens of extrahepatic CC (EHCC) and to evaluate the efficacy of CC cells with CSC-like properties by Notch signaling blockade. Methods: First, the expression of Notch1, 2, 3, 4 and Hes-1 was examined by immunohistochemistry in 132 resected EHCC specimens. The clinicopathological characteristics in the expression of Notch receptors and Hes-1 were investigated. Second, GSI IX, which is a γ-secretase-inhibitor, was used for Notch signaling blockade in the following experiment. Alterations of the subpopulation of CD24+CD44+ cells, which are surface markers of CSCs in EHCC, after exposure with GSI IX, gemcitabine (GEM), and the combination of GSI IX plus GEM were assessed by flow cytometry using the human CC cell lines, RBE, HuCCT1 and TFK-1. Also, anchorage-independent growth and mice tumorigenicity in the cells recovered by regular culture media after GSI IX exposure were assessed. Results: Notch1, 2, 3, 4 and Hes-1 in the resected EHCC specimens were expressed in 50.0, 56.1, 42.4, 6.1, and 81.8% of the total cohort, respectively. Notch1 and 3 expressions were associated with poorer histological differentiation (P = 0.008 and 0.053). The patients with the expression of at least any one of Notch1-3 receptors, who were in 80.3% of the total, exhibited poorer survival (P = 0.050). Similarly, the expression of Hes-1 tended to show poor survival (P = 0.093). In all of the examined CC cell lines, GSI IX treatment significantly diminished the subpopulation of CD24+CD44+ cells. Although GEM monotherapy relatively increased the subpopulation of CD24+CD44+ cells in all lines, GSI IX plus GEM attenuated it. Anchorage-independent growth and mice tumorigenicity were inhibited in GSI IX-pretreated cells in RBE and TFK-1 (P < 0.05). Conclusion: Aberrant Notch signaling is involved with EHCC. Inhibition of Notch signaling is a novel therapeutic strategy for targeting cells with CSC-like properties. [ABSTRACT FROM AUTHOR]
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- 2016
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175. Clinicopathological Characteristics of Young Patients With Pancreatic Cancer.
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Hidetoshi Eguchi, Hiroki Yamaue, Michiaki Unno, Masamichi Mizuma, Shin Hamada, Hisato Igarashi, Tamotsu Kuroki, Sohei Satoi, Yasuhiro Shimizu, Masaji Tani, Satoshi Tanno, Yoshiki Hirooka, Tsutomu Fujii, Atsushi Masamune, Kazuhiro Mizumoto, Takao Itoi, Shinichi Egawa, Yuzo Kodama, Masao Tanaka, and Tooru Shimosegawa
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- 2016
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176. Hepatic resection through an anterior approach employing a modified liver hanging maneuver in patients with a massive liver tumor severely oppressing the inferior vena cava
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Masanori, Suzuki, Michiaki, Unno, Yu, Katayose, Heigo, Takeuchi, Toshiki, Rikiyama, Tohru, Onogawa, Takeaki, Sato, Masamichi, Mizuma, Hideo, Ohtuka, and Seiki, Mastuno
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Male ,Carcinoma, Hepatocellular ,Rupture, Spontaneous ,Sutures ,Dissection ,Liver Neoplasms ,Vena Cava, Inferior ,Constriction, Pathologic ,Middle Aged ,Hepatitis B ,Surgical Instruments ,Liver ,Hepatectomy ,Humans ,Neoplasm Invasiveness ,Ligation ,Tomography, Spiral Computed ,Polyglycolic Acid ,Neoplasm Staging - Abstract
For a large hepatic neoplasm existing in the right hepatic lobe, hepatic resection using an anterior approach is required. We have reported an operative procedure for hepatic transection using absorbable polyglycolic acid tape. In patients with suspected tumor invasion of the inferior vena cava, on the other hand, considering the range of the residual tumor while sparing the inferior vena cava as much as possible, combined resection and reconstruction of the inferior vena cava is conducted only if operative curativity is expected. We conducted hepatic transection while maintaining the blood flow of the residual liver by applying the liver hanging maneuver method of Belghiti et al. and polyglycolic acid tape in patients with giant liver tumors of the right hepatic lobe compressing the hepatic inferior vena cava. Strong angled dissecting forceps were inserted into the ventral side of the inferior vena cava from the caudal side, and the tip was induced between hepatic veins. Two strips of polyglycolic acid tape were pinched with forceps and strongly ligated on the right and left sides of the cutoff line. Subsequently, hepatic transection was conducted using electrocautery spray coagulation and CUSA without blocking the inflow blood of the residual liver, and the right hepatic lobe was extirpated. This procedure has already been performed in 5 patients suspected of inferior vena cava invasion, and the inferior vena cava was able to be preserved in all the patients.
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- 2004
177. Adenovirus expressing mutant p27kip1 enhanced apoptosis against cholangiocarcinoma than adenovirus-p27kip1 wild type
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Tsuyoshi, Sasaki, Yu, Katayose, Masanori, Suzuki, Kuniharu, Yamamoto, Satoru, Shiraso, Masamichi, Mizuma, Michiaki, Unno, Heigo, Takeuchi, Choon-Taek, Lee, and Seiki, Matsuno
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Tumor Suppressor Proteins ,Apoptosis ,Cell Cycle Proteins ,Genetic Therapy ,Immunohistochemistry ,Precipitin Tests ,Cyclin-Dependent Kinases ,Adenoviridae ,Cholangiocarcinoma ,Bile Ducts, Intrahepatic ,Bile Duct Neoplasms ,Lac Operon ,Transduction, Genetic ,In Situ Nick-End Labeling ,Tumor Cells, Cultured ,Humans ,Cyclin-Dependent Kinase Inhibitor p27 - Abstract
The prognosis of cholangiocarcinoma is extremely poor despite the aggressive multidisciplinary cancer therapies that have been used clinically. Thus, it is imperative to develop new and effective treatments, such as gene therapy in order to treat this disease. p53 is the most common target for cancer gene therapy treatment. However, cholangiocarcinoma has a low frequency of p53 mutation, which makes this protein a poor candidate for gene therapy in this disease and another suitable gene therapy target must be found. p27kip1 is a universal cyclin-dependent kinase (CDK) inhibitor that blocks cell cycle progression and inhibits proliferation. Our previous reports have demonstrated the role of p27kip1 in the induction of apoptosis using a recombinant adenoviral vector expressing p27kip1 (Adp27) in several different human cancer cells. p27kip1 is regulated by two mechanisms composed of a ubiquitin-proteasome system and proteolytic processing system that requires the phosphorylation of p27kip1 on Thr-187 by the cyclinE/Cdk2 complex followed by proteolytic degradation.In this study, we focused our aim on the degradation of p27kip1 protein mediated by a recombinant adenoviral expressing a mutant p27kip1 (Adp27-mt), which has a mutation of Thr-187/Pro-188 (ACGCCC) to Met-187/Ile-188 (ATGATC).We observed that the mutated p27kip1 markedly inhibited ubiquitination and the subsequent degradation of p27kip1 when compared to wild type p27kip1. Consequently, we found that mutated p27kip1 induced a stronger induction of apoptosis and cell growth inhibition than wild type p27kip1 in cholangiocarcinoma cell lines TFK-1 and HuCCT-1. Furthermore, we demonstrated that Adp27-mt mainly caused G2/M arrest in the cell cycle progression and a decreased cyclinB1 and Cdc2 protein where as Adp27-wt mediated a G1/S arrest at 48 hours after infection.In this study, we showed that adenoviral vector expression of mutant p27kip1 protein inhibited degradation by the ubiquitin-proteasome system and strongly induced apoptosis and cell growth inhibition compared to wild type p27kip1. Thus recombinant adenovirus expressing mutant p27kip1 may be potentially useful for gene therapy against cholangiocarcinoma.
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- 2004
178. Adenovirus expressing p27KIP1 induces apoptosis against cholangiocarcinoma cells by triggering Fas ligand on the cell surface
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Kuniharu, Yamamoto, Yu, Katayose, Masanori, Suzuki, Michiaki, Unno, Tsuyoshi, Sasaki, Masamichi, Mizuma, Satoru, Shiraso, Hideo, Ohtuka, Kenneth H, Cowan, Prem, Seth, and Seiki, Matsuno
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Gene Expression Regulation, Viral ,Fas Ligand Protein ,Lung Neoplasms ,Membrane Glycoproteins ,Tumor Suppressor Proteins ,Apoptosis ,Breast Neoplasms ,Cell Cycle Proteins ,Genetic Therapy ,Adenoviridae ,Cholangiocarcinoma ,Gene Expression Regulation, Neoplastic ,Bile Duct Neoplasms ,Transduction, Genetic ,Tumor Cells, Cultured ,Humans ,RNA, Messenger ,Cyclin-Dependent Kinase Inhibitor p27 - Abstract
The prognosis of patients with cholangiocarcinoma is poor because of the difficulty of surgical curative resection. Therefore, other effective treatments must be developed especially those involving gene therapy. p27kip1, one of the cyclin-dependent kinase inhibitors, is known to limit proliferation of the cells. Our previous reports have shown that the overexpression of p27kip1 by a recombinant adenoviral vector expressing p27kip1 (Adp27) induces apoptosis. However, the mechanism of the Adp27-mediated apoptosis is not still resolved. Activation of the Fas pathway is one of the important gates for apoptosis. In this report, we examined whether p27kip1-induced apoptosis is closely related to the Fas/Fas ligand (FasL) system.After infection of Adp27, flow cytometric analysis showed that Fas ligand was expressed on the cell surface of cholangiocarcinoma cell lines (TFK-1). In spite of detecting the cell surface expression of Fas ligand, overexpression of p27kip1 increased no amount of Fas ligand in mRNA by quantitative RT-PCR and protein level by Western blot. In addition, the immunocytochemical analysis showed that Fas ligand was adequately stored within the cytosol of TFK-1 cells. More interestingly, Adp27-induced apoptosis was completely inhibited by the neutralizing antibody of Fas ligand (NOK-1). This result suggests that overexpression of p27kip1 may deliver Fas ligand to the cell surface and mainly utilizes the Fas pathway as a gate of apoptosis.This is the first report to prove that Adp27-mediated apoptosis utilizes the Fas pathway by delivering Fas ligand to the cell surface.
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- 2003
179. Can surgical resection be acceptable in pancreatic cancer patients with positive peritoneal washing cytology?
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Sohei Satoi, Goro Honda, Masamichi Mizuma, Ippei Matsumoto, Masayuki Sho, Hiroki Yamaue, Manabu Kawai, Yoshiyuki Nakajima, Sadaki Asari, Yoshiaki Murakami, Fuyuhiko Motoi, Hiroaki Yanagimoto, Kenichiro Uemura, A-Hon Kwon, Tomohisa Yamamoto, and Masanao Kurata
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Surgical resection ,medicine.medical_specialty ,Hepatology ,business.industry ,Pancreatic tissue ,Endocrinology, Diabetes and Metabolism ,Computer processing ,Gastroenterology ,Venous phase ,medicine.disease ,Peritoneal washing ,Surgery ,Pancreatic cancer ,Cytology ,medicine ,Pancreatitis ,Radiology ,business - Abstract
s / Pancreatology 14 (2014) S1eS129 S90 We got such digits in case of chronic pancreatitis (in venous phase of the study) e F11⁄43,21 [2,91-3,33] (P
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- 2014
180. Low CD274 expression increases tumorigenesis and cancer stem cell phenotypes in cholangiocarcinoma. Anti-CD274 staining of a clinical specimen from a patient with cholangiocarcinoma by surgical resection
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Hiroyuki Endo, Nobuyuki Tanaka, Koji Muramoto, Michiaki Unno, Misa Yokoyama, Masamichi Mizuma, Kazunori Yamaguchi, Takayuki Nakagawa, Masaaki Shiina, Ikuro Sato, Kazuo Sugamura, Keiichi Tamai, Mao Nakamura, Mai Mochizuki, and Kennichi Satoh
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Surgical resection ,Cancer Research ,Pathology ,medicine.medical_specialty ,business.industry ,General Medicine ,medicine.disease_cause ,Phenotype ,Staining ,Oncology ,Cancer stem cell ,Medicine ,business ,Carcinogenesis - Published
- 2014
181. Neoadjuvant chemotherapy with gemcitabine and S-1 for resectable and borderline pancreatic ductal adenocarcinoma: A prospective, multi-institutional, phase II trial
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Shinichi Takemura, Yu Katayose, Fuminori Ono, Masanori Akada, Hiromune Shimamura, Michiaki Unno, Fumiyoshi Fujishima, Masamichi Mizuma, Masaya Oikawa, Fuyuhiko Motoi, Shigeru Ottomo, Kazuyuki Ishida, Kei Nakagawa, Takaho Okada, and Shinichi Egawa
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Oncology ,Cancer Research ,medicine.medical_specialty ,Chemotherapy ,Pancreatic ductal adenocarcinoma ,business.industry ,medicine.medical_treatment ,Complete resection ,Gemcitabine ,Internal medicine ,medicine ,Clinical endpoint ,First line chemotherapy ,business ,Survival rate ,Therapeutic strategy ,medicine.drug - Abstract
283 Background: Although surgical resection is the only curative treatment for pancreatic ductal adenocarcinoma (PDAC), recurrence rates are very high even if complete resection is performed. Accordingly, a new therapeutic strategy against PDAC is needed. Combination with gemcitabine and S-1 (GS) as first line chemotherapy is promising. The purpose of this study is to evaluate the feasibility and efficacy of GS for resectable and borderline PDAC in the neoadjuvant chemotherapy (NAC). Methods: This study is a prospective, multi-institutional, single-arm, phase II trial. Neoadjuvant chemotherapy with gemcitabine and S-1(NAC-GS) for resectable and borderline PDAC was performed as follows. Gemcitabine was given at a dose of 1,000 mg/m2 on days 1 and 8 of each cycle. S-1 was administered orally at a dose of 40 mg/m2 twice daily for the first 14 consecutive days followed by a 7-day rest. Each cycle was repeated every 21 days. The primary endpoint was the 2-year survival rate. Secondary endpoints were feasibility, resection rate, pathological effect, recurrence-free survival and tumor marker status. Results: 36 patients were enrolled between 2008 and 2010. 35 were eligible for participation in this trial. The most common toxicity was neutropenia in response to 90% of the relative dose intensity. Radiological tumor shrinkage and decreases of CA19-9 levels were seen in 69% and 89%, respectively. R0 resection rate was 87%, and the morbidity rate (40%) was acceptable. The 2-year survival rate of the total cohort was 45.7%. Patients undergoing surgical resection without distant metastases after NAC-GS (n=27) showed an increased median overall survival (34.7 months), compared with 10.0 months for resection with distant metastases or non-resection (p=0.0017). Conclusions: NAC-GS is safe and well tolerated in a multi-institutional setting. NAC-GS is encouraging patients with resectable and borderline PDAC because of better outcomes. Clinical trial information: UMIN-000001504.
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- 2014
182. Reappraisal of Total Pancreatectomy in 45 Patients With Pancreatic Ductal Adenocarcinoma in the Modern Era Using Matched-Pairs Analysis.
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Sohei Satoi, Yoshiaki Murakami, Fuyuhiko Motoi, Masayuki Sho, Ippei Matsumoto, Kenichiro Uemura, Manabu Kawai, Masanao Kurata, Hiroaki Yanagimoto, Tomohisa Yamamoto, Masamichi Mizuma, Michiaki Unno, Shoichi Kinoshita, Takahiro Akahori, Makoto Shinzeki, Takumi Fukumoto, Yasushi Hashimoto, Seiko Hirono, Hiroki Yamaue, and Goro Honda
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- 2016
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183. Surgical anatomy of the right hepatic artery in Rouviere's sulcus evaluated by preoperative multidetector-row CT images.
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Shuichi Aoki, Masamichi Mizuma, Hiroki Hayashi, Kei Nakagawa, Takanori Morikawa, Fuyuhiko Motoi, Takeshi Naitoh, Shinichi Egawa, and Michiaki Unno
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LYMPH nodes ,HEPATIC artery ,COMPUTED tomography ,CHOLANGIOCARCINOMA ,INFARCTION ,PREOPERATIVE care - Abstract
Background: Lymph node dissection in Rouviere's sulcus (RS) is essential during left-sided hepatectomy and caudate lobectomy for hilar cholangiocarcinoma. However, the small segmental or subsegmental arteries (SA/SSA) are often encountered in RS and must be preserved to prevent critical complications, such as liver infarction or liver failure. The aim of this study is to elucidate the anatomy of SA/SSA around RS, which should be understood preoperatively. Methods: Between January 2008 and April 2013 from a total of 124 consecutive patients with hilar cholangiocarcinoma, preoperative multidetector-row computed tomography (MDCT) images were obtained at our institution and evaluated. The bifurcation patterns of the SA/SSA, the courses of the posterior SA/SSA and the bifurcation site of the SA/SSA were investigated using MDCT images. Results: The typical form, in which right hepatic artery (RHA) bifurcated into the anterior (Aant) and posterior (Apost) hepatic artery and thereafter, Aant/Apost bifurcated into the SA and SSA, was observed in 75 patients (60.5 %). On the other hand, the atypical forms, in which the SA/SSA were independently branched off from RHA before the main bifurcation of the Aant and Apost, were observed in 43 patients (34.7 %). The prior branched arteries supplied the whole or ventral area of segment VI (A6 or A6a) in 11 patients (8.9 %), which was most commonly observed in the atypical form. 15 patients (34.9 %) of the 43 patients with atypical form had partially supraportal posterior branches, that showed early-bifurcated posterior SA/SAA following supraportal course, while the other posterior SA/SSA followed infraportal course. The SA/SSA were extrahepatically bifurcated in 82 patients (66.1 %), comprised of all 43 atypical form and 39 of typical form, while the SA/SSA were intrahepatically bifurcated in remaining 36 patients of typical forms (29.0 %). Conclusion: The extrahepatic bifurcation of the SA/SSA from RHA was relatively common. The early-bifurcated SA/SSA was often observed (34.7 % of total cohort) and, in 34.8 % of those atypical forms, posterior SA/SSA from RHA followed a supraportal course. The detailed preoperative knowledge of the anatomy, including SA/SSA, is crucial for left-sided hepatectomy for hilar cholangiocarcinoma. [ABSTRACT FROM AUTHOR]
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- 2016
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184. Giant solid pseudopapillary neoplasm of the pancreas in a middle-aged man: A case report
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Shinichi Egawa, Masahiro Iseki, Natsumi Sakata, Masamichi Mizuma, Takeshi Aoki, Hideki Hayashi, Takaho Okada, Yu Katayose, Koji Fukase, Shigeru Ottomo, Takanori Morikawa, Kei Nakagawa, Hideo Ohtsuka, Michiaki Unno, Takeshi Naitoh, Fuyuhiko Motoi, and Hiroshi Yoshida
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medicine.medical_specialty ,Hepatology ,biology ,business.industry ,Endocrinology, Diabetes and Metabolism ,Abdominal ct ,Gastroenterology ,Vimentin ,medicine.disease ,Epigastric pain ,Resection ,medicine.anatomical_structure ,medicine ,biology.protein ,Neoplasm ,Radiology ,Pancreas ,business ,Calcification ,Histological examination - Abstract
M. Iseki , M. Mizuma , H. Yoshida , T. Okada , K. Nakagawa, H. Hayashi , T. Morikawa , S. Ottomo, N. Sakata , H. Ohtsuka , K. Fukase , T. Aoki , F. Motoi , T. Naitoh , Y. Katayose , S. Egawa , M. Unno . Division of Hepato-Biliary-Pancretic Surgery, Department of Surgery, Tohoku University Graduate School of Medicine, Japan Division of Integrated Surgery and Oncology, Department of Surgery, Tohoku University Graduate School of Medicine, Japan Introduction: A solid pseudopapillary neoplasm (SPN) of the pancreas is a rare neoplasm of low malignant potential. It typically afflicts in young women, but uncommon in men. We report giant solid pseudopapillary neoplasm of the pancreas in a middle-aged man. Case report: A 47-year-old manwas admitted to the previous hospital for continuous epigastric pain and bodyweight loss. A giantmasswas palpated in the upper abdominal area. The abdominal CT scan revealed 21 cmmass with central necrosis and peripheral calcification in the pancreas. This tumor showed enhanced solid component in the marginal area. The patient underwent total pancreatectomy with portal vein resection and reconstruction. In the resected specimen, 26 cm tumor of the pancreas, surrounded by a fibrous pseudocapsule, gave rise to central necrosis and intratumoral hemorrhage. Histological examination revealed that the tumor cells with enlarged nucleus and granular eosinophillic cytoplasm were arranged in sheets and nests, forming pseudopapilla formation. They were immunohistologically positive for CD10 and vimentin. Since nuclear accumulation of beta-catenin protein was shown, this tumor was pathologically diagnosed with SPN. This had malignant potential, indicated by venous invasion. Discussion: This case show atypical clinical feature (age, gender) and typical radiographical feature, including the enhancement of solid component and peripheral calcification. Giant SPN with central necrosis and intratumoral hemorrhage is similar to other giant pancreatic tumors, such as neuroendcrine tumor. Giant SPN is difficult to diagnose by imaging modalities preoperatively, especially in men.
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- 2013
185. Surgical treatment for chronic pancreatitis, discussion of drainage and total pancreatectomy with islet autotransplantation
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Shinichi Egawa, Hideki Hayashi, Hiroshi Yoshida, Takeshi Aoki, Yu Katayose, Koh Miura, Takeshi Naitoh, Takanori Morikawa, Shigeru Ottomo, Naoaki Sakata, Gumpei Yoshimatsu, Kei Nakagawa, Masaharu Ishida, Masamichi Mizuma, Takaho Okada, Koji Fukase, Michiaki Unno, and Fuyuhiko Motoi
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geography ,medicine.medical_specialty ,geography.geographical_feature_category ,Hepatology ,Total pancreatectomy ,business.industry ,Endocrinology, Diabetes and Metabolism ,medicine.medical_treatment ,General surgery ,Gastroenterology ,Islet ,medicine.disease ,Autotransplantation ,Medicine ,Pancreatitis ,Drainage ,Surgical treatment ,business - Published
- 2013
186. Intraoperative Ultrasound Examination Is Useful for Monitoring Transplanted Islets
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Michiaki Unno, Susumu Satomi, Gumpei Yoshimatsu, Masafumi Goto, Fuyuhiko Motoi, Naoaki Sakata, and Masamichi Mizuma
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Transplantation ,medicine.medical_specialty ,business.industry ,medicine ,Radiology ,business ,Intraoperative ultrasound - Published
- 2012
187. 278 CD133-expressing Cells Have Cancer Stem Cell-like Properties in Cholangiocarcinoma
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Y. Kitamura, Fuyuhiko Motoi, Michiaki Unno, Yu Katayose, T. Rikiyama, Masamichi Mizuma, Shigeru Ottomo, Shinichi Egawa, and Hiroshi Yoshida
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Oncology ,Cancer Research ,medicine.medical_specialty ,Cancer stem cell ,Internal medicine ,medicine ,Biology - Published
- 2012
188. Potential utility of eGFP-expressing NOG mice (NOG-EGFP) as a high purity cancer sampling system
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Yo Kitamura, Toshiki Rikiyama, Naoaki Sakata, Shinichi Egawa, Kei Nakagawa, Masamichi Mizuma, Akira Horii, Hiroki Hayashi, Takaho Okada, Kentaro Shima, Michiaki Unno, Yu Katayose, Noriyuki Omura, Naoto Ishii, and Fuyuhiko Motoi
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Cancer Research ,Pathology ,medicine.medical_specialty ,Stromal cell ,Cell Survival ,Green Fluorescent Proteins ,Mice, SCID ,Biology ,lcsh:RC254-282 ,Flow cytometry ,Separation ,Cell Line ,Cholangiocarcinoma ,Mice ,Mice, Inbred NOD ,medicine ,Animals ,Humans ,Viability assay ,Cancer ,Severe combined immunodeficiency ,medicine.diagnostic_test ,Research ,Xenograft ,NOG-EGFP mouse ,Cell sorting ,medicine.disease ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,Flow Cytometry ,Molecular biology ,Pancreatic Neoplasms ,Disease Models, Animal ,Bile Ducts, Intrahepatic ,Phenotype ,Oncology ,Bile Duct Neoplasms ,Cell culture ,Cancer cell ,Female ,Neoplasm Transplantation - Abstract
Purpose It is still technically difficult to collect high purity cancer cells from tumor tissues, which contain noncancerous cells. We hypothesized that xenograft models of NOG mice expressing enhanced green fluorescent protein (eGFP), referred to as NOG-EGFP mice, may be useful for obtaining such high purity cancer cells for detailed molecular and cellular analyses. Methods Pancreato-biliary cancer cell lines were implanted subcutaneously to compare the tumorigenicity between NOG-EGFP mice and nonobese diabetic/severe combined immunodeficiency (NOD/SCID) mice. To obtain high purity cancer cells, the subcutaneous tumors were harvested from the mice and enzymatically dissociated into single-cell suspensions. Then, the cells were sorted by fluorescence-activated cell sorting (FACS) for separation of the host cells and the cancer cells. Thereafter, the contamination rate of host cells in collected cancer cells was quantified by using FACS analysis. The viability of cancer cells after FACS sorting was evaluated by cell culture and subsequent subcutaneous reimplantation in NOG-EGFP mice. Results The tumorigenicity of NOG-EGFP mice was significantly better than that of NOD/SCID mice in all of the analyzed cell lines (p Conclusions This method provides a novel cancer sampling system for molecular and cellular analysis with high accuracy and should contribute to the development of personalized medicine.
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- 2012
189. Imaging of transplanted islets by positron emission tomography, magnetic resonance imaging, and ultrasonography.
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Naoaki Sakata, Gumpei Yoshimatsu, Haruyuki Tsuchiya, Takeshi Aoki, Masamichi Mizuma, Fuyuhiko Motoi, Yu Katayose, Tetsuya Kodama, Shinichi Egawa, and Michiaki Unno
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- 2013
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190. Potential utility of eGFP-expressing NOG mice (NOG-EGFP) as a high purity cancer sampling system.
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Kentaro Shima, Masamichi Mizuma, Hiroki Hayashi, Kei Nakagawa, Takaho Okada, Naoaki Sakata, Noriyuki Omura, Yo Kitamura, Fuyuhiko Motoi, Toshiki Rikiyama, Yu Katayose, Shinichi Egawa, Naoto Ishii, Akira Horii, and Michiaki Unno
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LABORATORY mice , *CANCER cells , *CELL culture , *TUMORS , *CYSTS (Pathology) , *ONCOLOGY , *CELL lines , *TISSUES - Abstract
Purpose: It is still technically difficult to collect high purity cancer cells from tumor tissues, which contain noncancerous cells. We hypothesized that xenograft models of NOG mice expressing enhanced green fluorescent protein (eGFP), referred to as NOG-EGFP mice, may be useful for obtaining such high purity cancer cells for detailed molecular and cellular analyses. Methods: Pancreato-biliary cancer cell lines were implanted subcutaneously to compare the tumorigenicity between NOG-EGFP mice and nonobese diabetic/severe combined immunodeficiency (NOD/SCID) mice. To obtain high purity cancer cells, the subcutaneous tumors were harvested from the mice and enzymatically dissociated into single-cell suspensions. Then, the cells were sorted by fluorescence-activated cell sorting (FACS) for separation of the host cells and the cancer cells. Thereafter, the contamination rate of host cells in collected cancer cells was quantified by using FACS analysis. The viability of cancer cells after FACS sorting was evaluated by cell culture and subsequent subcutaneous reimplantation in NOG-EGFP mice. Results: The tumorigenicity of NOG-EGFP mice was significantly better than that of NOD/SCID mice in all of the analyzed cell lines (p < 0.01). Sorting procedures enabled an almost pure collection of cancer cells with only slight contamination by host cells. Reimplantation of the sorted cancer cells formed tumors again, which demonstrated that cell viability after sorting was well maintained. Conclusions: This method provides a novel cancer sampling system for molecular and cellular analysis with high accuracy and should contribute to the development of personalized medicine. [ABSTRACT FROM AUTHOR]
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- 2012
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191. Adenovirus Expressing Mutant p27 kip1 Enhanced Apoptosis and Inhibited the Growth of Xenografted Human Breast Cancer.
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Tsuyoshi Sasaki, Yu Katayose, Kuniharu Yamamoto, Masamichi Mizuma, Satoru Shiraso, Shinichi Yabuuchi, Akira Oda, Toshiki Rikiyama, Masaya Oikawa, Toru Onogawa, Masanori Suzuki, Choon-Taek Lee, and Michiaki Unno
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GENE therapy ,BREAST cancer ,CANCER treatment ,TUMORS ,THERAPEUTICS ,CLINICAL medicine - Abstract
Abstract Purpose To evaluate the anti-tumor effects of a novel adenovirus expressing mutant p27 kip1 (Adp27-mt), which consists of a mutation of Thr-187/Pro-188 to Met-187/Ile-188. Methods Using the human breast cancer cell lines, MDA-MB-231, ZR-75-1, and MCF-7, we tested Adp27-mt for cell cycle assay, growth inhibition assay, and TdT-mediated dUTP-biotin nick end labeling in a human breast cancer-grafted severe combined immunodeficiency (SCID) mouse model. Results The mutant p27 kip1 induced stronger apoptosis in the breast cancer cell lines than adenovirus expressing wild-type p27 kip1 (Adp27-wt). Adp27-mt inhibits cell growth significantly; being about 5- and 3.5-fold stronger for IC50 than Adp27-wt in the breast cancer cell lines, MDA-MD-231 and ZR-75-1, respectively. In the human breast cancer-grafted SCID mouse model, Adp27-mt induced tumor regression and antitumor effects significantly better than Adp27-wt. Furthermore, Adp27-mt mainly caused G2/M arrest in the cell cycle progression, whereas Adp27-wt mediated a G1/S arrest 48 h after infection. Conclusion The mutant p27 kip1 protein induced apoptosis, and inhibited cell growth more efficiently with stronger anti-tumor effects than wild-type p27 kip1 . Thus, the recombinant adenovirus expressing mutant p27 kip1 could be useful in gene therapy against breast cancer. [ABSTRACT FROM AUTHOR]
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- 2007
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192. Surgical anatomy of the right hepatic artery in Rouviere’s sulcus evaluated by preoperative multidetector-row CT images
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Shuichi Aoki, Shinichi Egawa, Takanori Morikawa, Hiroki Hayashi, Fuyuhiko Motoi, Kei Nakagawa, Michiaki Unno, Masamichi Mizuma, and Takeshi Naitoh
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Adult ,Male ,0301 basic medicine ,medicine.medical_specialty ,medicine.medical_treatment ,Cholangiocarcinoma ,Right hepatic arteries ,Postoperative complications ,03 medical and health sciences ,Hepatic Artery ,0302 clinical medicine ,Text mining ,Surgical anatomy ,stomatognathic system ,Multidetector Computed Tomography ,medicine ,Hepatectomy ,Humans ,Lymph node ,Retrospective Studies ,Aged, 80 and over ,Right hepatic artery ,business.industry ,General Medicine ,Middle Aged ,Sulcus ,Surgery ,Dissection ,stomatognathic diseases ,medicine.anatomical_structure ,Bile Duct Neoplasms ,Preoperative Period ,Lymph Node Excision ,Female ,030211 gastroenterology & hepatology ,030101 anatomy & morphology ,Radiology ,Tomography, X-Ray Computed ,business ,Research Article ,Artery - Abstract
Background Lymph node dissection in Rouviere’s sulcus (RS) is essential during left-sided hepatectomy and caudate lobectomy for hilar cholangiocarcinoma. However, the small segmental or subsegmental arteries (SA/SSA) are often encountered in RS and must be preserved to prevent critical complications, such as liver infarction or liver failure. The aim of this study is to elucidate the anatomy of SA/SSA around RS, which should be understood preoperatively. Methods Between January 2008 and April 2013 from a total of 124 consecutive patients with hilar cholangiocarcinoma, preoperative multidetector-row computed tomography (MDCT) images were obtained at our institution and evaluated. The bifurcation patterns of the SA/SSA, the courses of the posterior SA/SSA and the bifurcation site of the SA/SSA were investigated using MDCT images. Results The typical form, in which right hepatic artery (RHA) bifurcated into the anterior (Aant) and posterior (Apost) hepatic artery and thereafter, Aant/Apost bifurcated into the SA and SSA, was observed in 75 patients (60.5 %). On the other hand, the atypical forms, in which the SA/SSA were independently branched off from RHA before the main bifurcation of the Aant and Apost, were observed in 43 patients (34.7 %). The prior branched arteries supplied the whole or ventral area of segment VI (A6 or A6a) in 11 patients (8.9 %), which was most commonly observed in the atypical form. 15 patients (34.9 %) of the 43 patients with atypical form had partially supraportal posterior branches, that showed early-bifurcated posterior SA/SAA following supraportal course, while the other posterior SA/SSA followed infraportal course. The SA/SSA were extrahepatically bifurcated in 82 patients (66.1 %), comprised of all 43 atypical form and 39 of typical form, while the SA/SSA were intrahepatically bifurcated in remaining 36 patients of typical forms (29.0 %). Conclusion The extrahepatic bifurcation of the SA/SSA from RHA was relatively common. The early-bifurcated SA/SSA was often observed (34.7 % of total cohort) and, in 34.8 % of those atypical forms, posterior SA/SSA from RHA followed a supraportal course. The detailed preoperative knowledge of the anatomy, including SA/SSA, is crucial for left-sided hepatectomy for hilar cholangiocarcinoma.
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193. Locally advanced pancreatic cancer successfully treated by distal pancreatectomy with celiac axis resection (DP-CAR) after S-1 with radiation therapy followed by gemcitabine/nab-paclitaxel therapy: a case report
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Takanori Morikawa, Tatsuyuki Takadate, Shinichi Egawa, Keigo Murakami, Kyohei Ariake, Kunihiro Masuda, Fuyuhiko Motoi, Naoaki Sakata, Kei Nakagawa, Hideo Ohtsuka, Michiaki Unno, Takeshi Naitoh, Shimpei Maeda, Hiroki Hayashi, Koji Fukase, and Masamichi Mizuma
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medicine.medical_specialty ,medicine.medical_treatment ,Case Report ,Splenic artery ,Nab-paclitaxel ,03 medical and health sciences ,0302 clinical medicine ,Celiac artery ,medicine.artery ,Pancreatic cancer ,medicine ,Superior mesenteric artery ,DP-CAR ,Common hepatic artery ,business.industry ,Cancer ,medicine.disease ,Chemoradiation therapy ,Gemcitabine ,Surgery ,Radiation therapy ,030220 oncology & carcinogenesis ,030211 gastroenterology & hepatology ,Locally advanced ,Radiology ,business ,medicine.drug - Abstract
Background The prognosis for pancreatic cancer remains dismal because many patients are diagnosed with unresectable cancer at the initial diagnosis. Recently, conversion surgery was reported as an effective treatment for initially unresectable pancreatic cancer with a favorable response to non-surgical treatment lasting over 240 days. Here, we describe a case of locally advanced pancreatic cancer (LAPC) successfully resected after treatment with S-1 and radiation followed by gemcitabine/nab-paclitaxel therapy. Case presentation A 73-year-old man with LAPC was referred to our hospital. Computed tomography findings revealed a 2.5-cm mass in the pancreatic body that had invaded the celiac artery, common hepatic artery, and splenic artery. Superior mesenteric artery (SMA) encasement was not observed, but tumor abutment over 180° with the main tumor was detected. Staging laparoscopy showed no findings of distant metastasis, and washing cytology revealed no malignancy. He was diagnosed with unresectable pancreatic cancer. Treatment with S-1 with radiation therapy followed by gemcitabine with nab-paclitaxel was performed. Six months after the initial treatment, the tumor size had decreased to 1.2 cm, and encasement of the main artery was diminished. Though abutment to the main artery, including the SMA, was still detected, distal pancreatectomy with celiac artery resection was performed. The histopathological findings around the celiac artery revealed fibrous changes with an Evans classification of grade IIb. There was no residual cancer at the periphery; thus, R0 resection was achieved. The patient has been healthy and without recurrence for more than 12 months since the initial treatment. Conclusions Gemcitabine/nab-paclitaxel therapy revealed high response rate for metastasic pancreatic cancer (PC), but the effect for LAPC proposing conversion surgery was not well discussed. In this case, we achieve R0 resection combined with chemoradiation therapy and gemcitabine/nab-paclitaxel therapy. This regimen was also effective for LAPC and may be used to increase the population of conversion surgery by its high response rate.
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