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E2FBP1 antagonizes the p16^(INK4A)-Rb tumor suppressor machinery for growth suppression and cellular senescence by regulating promyelocytic leukemia protein stability

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International Journal of Oral Science 2011年第4期3卷 200-208页

作者： Yayoi Fukuyo Akiko takahashi Eiji Hara Nobuo Horikoshi Tej K. Pandita Takuma Nakajima Department of Immunology Tulane National Primate Research Center Section of Bacterial Pathogenesis Graduate School Tokyo Medical and Dental University Division of Cancer Biology The Cancer Institute Japanese Foundation for Cancer Research Division of Molecular Radiation Biology Department of Radiation Oncology University of Texas Southwestern Medical Center

Cellular senescence is an irreversible cell cycle arrest triggered by the activation of oncogenes or mitogenic signaling as well as the enforced expression of tumor suppressors such as p53, p16INK4A and promyelocytic leukemia protein （PML） in normal cells. E2F-binding protein 1 （E2FBP1）, a transcription regulator for E2F, induces PML reduction and suppresses the formation of PML-nuclear bodies, whereas the down-regulation of E2FBP1 provokes the PML-dependent premature senescence in human normal fibroblasts. Here we report that the depletion of E2FBP1 induces the accumulation of PML through the Ras-dependent activation of MAP kinase signaling. The cellular levels of p16INK4A and p53 are elevated during premature senescence induced by depletion of E2FBP1, and the depletion of p16INK4A, but not p53 rescued senescent cells from growth arrest. Therefore, the premature senescence induced by E2FBP1 depletion is achieved through the pl6INK4A-Rb pathway. Similar to human normal fibroblasts, the growth inhibition induced by E2FBP1 depletion is also observed in human tumor cells with intact p16INK4A and Rb. These results suggest that E2FBP1 functions as a critical antagonist to the pI6INK4A-Rb tumor suppressor machinery by regulating PML stability.

关键词： E2F-binding protein 1 senescence cell cycle ubiquitin promyelocytic leukemia protein

In-Process Diameter Measurement Technique for Micro-Optical Fiber with Standing Wave Illumination

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Nanomanufacturing and Metrology 2021年第1期4卷 28-36页

作者： Masaki Michihata Zhao Zheng Daiki Funaiwa Sojiro Murakami Shotaro Kadoya Satoru takahashi Department of Precision Engineering The University of Tokyo7-3-1 HongoBunkyoTokyo 113-8654Japan Research Center for Advanced Science and Technology The University of Tokyo4-6-1 KomabaMeguroTokyo 153-8904Japan

In this paper,we propose an in-process measurement method of the diameter of micro-optical fiber such as a tapered optical *** proposed technique is based on analyzing optically scattered light generated by standing wave *** proposed method is significant in that it requires an only limited measurement range and does not require a high dynamic range *** properties are suitable for in-process *** experiment verified that the proposed method could measure a fiber diameter as stable as±0.01μm under an air turbulence *** a result of comparing the measured diameter distribution with those by scanning electron microscopy,it was confirmed that the proposed method has a measurement accuracy better than several hundred nanometers.

关键词： Micro-fiber In-process measurement Mi scattering theory Standing wave Diameter

Short and long-term outcomes of endoscopic balloon dilatation for Crohn's disease strictures

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World Journal of Gastroenterology 2013年第1期19卷 86-91页

作者： Katsuya Endo Seiichi takahashi Hisashi Shiga Yoichi Kakuta Yoshitaka Kinouchi Tooru Shimosegawa Division of Gastroenterology Tohoku University Graduate School of MedicineSendai 980-8574Japan

AIM:To investigate the short and long-term outcomes of endoscopic balloon dilatation(EBD) for Crohn's disease(CD) ***:Between January 1995 and December 2011,47 EBD procedures were performed in 30 patients(8 females and 22 males) with *** patients had strictures through which an endoscope could not pass,and symptoms of these strictures included abdominal pain,abdominal fullness,nausea,and/or *** 47 strictures included 17 anastomotic and 30 de novo *** and dilatation were performed under conscious sedation with intravenous diazepam or *** dilatations were all performed using through-the-scope balloons with diameters from 8 mm to 20 mm on inflation and lengths of 30-80 *** dilatation session consisted of two to four,3-min multistep inflations of the balloon,repeated at intervals of 1 wk until adequate dilatation(up to 15-20 mm in diameter) was *** follow-up data were collected from medical records and analyzed *** success was defined as passage of the scope through the stricture after *** outcomes were analyzed focusing on interventionfree survival and surgery-free survival demonstrated by the Kaplan-Meier method.(Intervention-free meant cases in which neither endoscopic balloon re-dilatation nor surgery was needed after the first dilatation during the observation period).The log rank test was used to evaluate the difference in long-term outcomes between anastomotic and de novo stricture ***:Primary success was achieved in 44 of the 47 strictures(93.6%).Balloon dilatations failed in 3 cases(6.4%).In 1 case,EBD was a technical failure because the guide-wire could not be passed through the stricture which showed severe adhesion and was a flexural lesion of the *** 2 cases,unexpected perforations occurred immediately after balloon *** the 47 treatments,complications occurred in 5(10.6%).All 5 patients had de novo *** suffered bleeding

关键词： Crohn’s disease Endoscopic balloon dilatation Stricture Anastomotic De novo Outcome

Influence of pulsed electric field on enzymes, bacteria and volatile flavor compounds of unpasteurized sake

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Plasma Science and Technology 2018年第4期20卷 51-56页

作者： Takamasa OKUMURA Taro YAEGASHI Takahiro FUJIWARA Katsuyuki takahashi Koichi TAKAKI Tomo KUDO Institute of Fluid Science Tohoku University Department of Systems Innovation Engineering Iwate University Washinoo Co. Ltd

A pulsed electric field(PEF) was applied to unpasteurized sake at constant temperatures, at which α-amylase was not inactivated. We adjusted the input energy to be identical for the temperatures by changing the number of PEF application, because the current significantly increased with the temperature, even the amplitude of the applied voltage was identical. As a result, the α-amylase was seemed to be inactivated by PEF application, not due to thermal *** glucoamylase was significantly inactivated by PEF. Moreover, the acid carboxypeptidase was inactivated by PEF at 4 °C but significantly activated at 25 °C. These results show that the sensitivity of enzyme to PEF application differs depending on the types of enzyme and treatment temperature. On the other hand, the colony number of bacteria was remarkably decreased, but the amount of the volatile flavor compounds was not decreased by PEF application.

关键词： pulsed electric field enzyme activity bacteria inactivation vulnerable molecules unpasteurized sake electroporation

Endoscopic submucosal dissection as excisional biopsy for anorectal malignant melanoma:A case report

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World Journal of Clinical Cases 2019年第13期7卷 1652-1659页

作者： Shigeo Manabe Yoshio Boku Michiyo Takeda Fumitaka Usui Ikuhiro Hirata Shuji takahashi Department of Gastroenterology Kouseikai Takeda Hospital Kyoto 600-8558 Japan Fujita Clinic 67 Gokiya-cho Oomiya-dori Shichijo-kudaru Shimogyo-ku Kyoto 600-8267 Japan

BACKGROUND Anorectal malignant melanoma (AMM) is a rare disorder with an extremely poor prognosis. Although there is currently no consensus on the treatment methods for AMM, surgical procedures have been the most common treatment methods used until now. We recently encountered a case of AMM that we diagnosed using endoscopic submucosal dissection (ESD). To our knowledge, this is the first case of ESD for AMM, suggesting that ESD can potentially be a diagnostic and treatment method for AMM. CASE SUMMARY A 77-year-old woman visited our hospital with a chief complaint of anal bleeding and a palpable rectal mass. Colonoscopy revealed a 20-mm protruded lesion in the lower rectum. After obtaining biopsy specimens from the lesion, although a malignant rectal tumor was suspected, a definitive diagnosis was not made. Endoscopic ultrasonography revealed tumor invasion into the submucosal layer but not the muscular layer. Therefore, we performed an excisional biopsy using ESD. Immunohistochemical examination of the ESD-resected specimen revealed tumor cells positive for Human Melanin Black-45, Melan-A, and S-100. Moreover, the tumor cells lacked melanin pigment;thus, a diagnosis of amelanotic AMM was made. Although the AMM had massively invaded the submucosal layer and both lymphatic and venous invasion were present, we closely monitored the patient without any additional therapy on the basis of her request. Six months after ESD, local recurrence was detected, and the patient consented to wide local excision. CONCLUSION It is suggested that ESD is a potential diagnostic and treatment method for AMM.

关键词： Endoscopic submucosal dissection Anorectal malignant melanoma Endoscopic mucosal resection Case report

Recurrent renal cell carcinoma leading to a misdiagnosis of polycystic liver disease: A case report

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World Journal of Gastroenterology 2019年第18期25卷 2264-2270页

作者： Chen Liang Kazuhiro takahashi Masanao Kurata Shingo Sakashita Tatsuya Oda Nobuhiro Ohkohchi Department of Surgery University of Tsukuba Department of Diagnostic Pathology University of Tsukuba

BACKGROUND Polycystic liver disease(PCLD) with a large cystic volume deteriorates the quality of life of patients through substantial effects on the adjacent organs,recurrent cyst infections, cyst rupture, and hemorrhage. Surgical or radiological intervention is usually needed to alleviate these symptoms. We report a rare case of the cystic metastasis of renal cell carcinoma(RCC), which was misdiagnosed as PCLD, as a result of the clinical and radiological similarity between these *** SUMMARY A 74-year-old female who had undergone nephrectomy for papillary-type RCC(PRCC) was suffering from abdominal pain and the recurrent intracystic hemorrhage of multiple cysts in the liver. Imaging studies and aspiration cytology of the cysts showed no evidence of malignancy. With a diagnosis of autosomal dominant polycystic liver disease, the patient received hepatectomy for the purpose of mass reduction and infectious cyst removal. Surgery was performed without complications, and the patient was discharged on postoperative day 14. Postoperatively, the pathology revealed a diagnosis of recurrent PRCC with cystic *** This case demonstrates the importance of excluding the cystic metastasis of a cancer when liver cysts are observed.

关键词： Polycystic liver disease Polycystic kidney disease Cystic metastasis Renal cell carcinoma Case report

Stem cell-derived exosomes as a therapeutic tool for cardiovascular disease

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World Journal of Stem Cells 2016年第9期8卷 297-305页

作者： Etsu Suzuki Daishi Fujita Masao takahashi Shigeyoshi Oba Hiroaki Nishimatsu Institute of Medical Science St. Marianna University School of Medicine Department of Internal Medicine Faculty of Medicine University of Tokyo Department of Urology Faculty of MedicineUniversity of Tokyo

Mesenchymal stem cells(MSCs) have been used to treat patients suffering from acute myocardial infarction(AMI) and subsequent heart failure. Although it was originally assumed that MSCs differentiated into heart cells such as cardiomyocytes, recent evidence suggests that the differentiation capacity of MSCs is minimal and that injected MSCs restore cardiac function via the secretion of paracrine factors. MSCs secrete paracrine factors in not only naked forms but also membrane vesicles including exosomes containing bioactive substances such as proteins, messenger RNAs, and microR NAs. Although the details remain unclear, these bioactive molecules are selectively sorted in exosomes that are then released from donor cells in a regulated manner. Furthermore, exosomes are specifically internalized by recipient cells via ligand-receptor interactions. Thus, exosomes are promising natural vehicles that stably and specifically transport bioactive molecules to recipient cells. Indeed, stem cell-derived exosomes have been successfully used to treat cardiovascular disease(CVD), such as AMI, stroke, and pulmonary hypertension, in animal models, and their efficacy has been demonstrated. Therefore, exosome administration may be a promising strategy for the treatment of CVD. Furthermore, modifications of exosomal contents may enhance their therapeutic effects. Future clinical studies are required to confirm the efficacy of exosome treatment for CVD.

关键词： Exosomes Messenger RNA Cardiovascular disease Mesenchymal stem cells Stem cells MicroRNA

Voltammetric response of ferroceneboronic acid to diol and phenolic compounds as possible pollutants

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Journal of Environmental Sciences 2011年第6期23卷 1027-1032页

作者： Shigehiro takahashi Naoyuki Abiko Nobuhiro Haraguchi Hiroyuki Fujita Eriko Seki Tetsuya Ono Kentaro Yoshida Jun-ichi Anzai Graduate School of Pharmaceutical Sciences Tohoku UniversityAramakiAoba-kuSendai 980-8578Japan School of Pharmaceutical Sciences Ohu University31-1 MisumidoTomita-machiKoriyamaFukushima 963-8611Japan

A voltammetric determination of possible organic pollutants such as diol and phenolic compounds in water was studied using ferroceneboronic acid（FBA） as a redox-active marker.A cyclic voltammogram of FBA exhibited a pair of oxidation and reduction peaks at 230 and 170 mV at pH 7.0,respectively,while another pair of redox peaks was observed in the presence of diol or phenolic compounds *** results were rationalized based on the formation of boronate esters of FBA with the added *** changes in the redox peak currents were dependent on the concentration of the additives,suggesting a usefulness of FBA in the electrochemical determination of these compounds in water.

关键词： ferroceneboronic acid sugar phenolic compound cyclic voltammetry pollutants in water electrochemical determination

Earthworm fibrinolytic enzyme:anti-tumor activity on human hepatoma cells in vitro and in vivo

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Chinese Medical Journal 2007年第10期120卷 898-904页

作者： CHEN Hong Shoichi takahashi Michio Imamura Eiko Okutani ZHANG Zhi-guo Kazuaki Chayama CHEN Bao-an Department of Gastroenterology Affiliated Zhongda Hospital Southeast University Nanjing 210009 China Department of Medicine and Molecular Science Graduate School of Biomedical Sciences Hiroshima University Hiroshima 734-8551 Japan Institute of Biochemistry and Immunology Nanjing Agricultural University Nanjing 210095 China

Background The earthworm fibrinolytic enzyme （EFE） is a complex protein enzyme that is widely distributed in the earthworm＇s digestive cavity. Possessing strong protein hydrolysis activity, EFE not only has a direct effect on fibrin, but also can activate plasminogen. Its therapeutic and preventative effects on thrombosis-related disease have been confirmed clinically. Recently, there has been increased interest in the anti-tumor activity of EFE. In this study, the anti-tumor activity of EFE, isolated from Eisenia foetida, on human hepatoma cells was evaluated in vitro and in vivo. The potential mechanisms involved were also studied. Methods In vitro experiments were performed in four human hepatoma cell lines： HLE, Huh7, PLC/PRF/5 and HepG2. After treatment with EFE in various concentrations, the inhibition of the rate of cell proliferation was measured. For the in vivo studies, tumor-bearing models xenografted with Huh7 cells were developed in nude mice, and then the mice were fed with EFE once a day for 4 weeks, and the control group received only saline. An inhibitory effect on tumor growth was observed. Also, apoptosis was observed with flow cytometric assay and fluorescent dye staining with acridine orange and ethidium bromide （AO/EB）. The expression of matrix metalloproteinase 2 （MMP-2） were detected by Western blotting assay. Results After treatment with various concentrations of EFE, the proliferation of all hepatoma cell lines was suppressed to varying degrees in vitro. The IC50 for HLE, Huh7, PLC/PCF/5 and HepG2 were 2.11, 5.87, 25.29 and 17.30 uku/ml, respectively. After administration of EFE orally for 4 weeks, the growth of tumor xenograft of Huh7 cells in nude mice was significantly inhibited in vivo. The tumor inhibitory rates in the EFE 500 uku/（kg·d） and 1000 uku/（kg·d） groups were 46.08% （compared with control group, P=0.026） and 57.52% （compared with control group, P=0.002） respectively. Meanwhile, the average weight of body, spleen or thymus

关键词： earthworm fibrinolysin liver neoplasm mice, nude apoptosis,