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Persimmon Leaf Flavonols Enhance the Anti-Cancer Effect of Heavy Ion Radiotherapy on Murine Xenograft Tumors

Journal of Cancer Therapy 2013年第7期4卷 1150-1157页

作者： Kayoko Kawakami hiroshi nishida Naoto Tatewaki Kiyomi Eguchi-Kasai Kazunori Anzai Takahiro Eitsuka Tetsuya Konishi Masao Hirayama Laboratory of Nutritional Biochemistry Niigata University of Pharmacy & Applied Life Sciences Niigata Japan National Institute of Radiological Sciences Chiba Japan

The cell cycle checkpoint system play a pivotal role in the cellular DNA damage response, and the discovery of checkpoint inhibitors is expected to sensitize current cancer therapies. Checkpoint signaling cascades are critically modulated by ATM (ataxia telangiectasia-mutated) and its related molecules. Generally, ATM primarily responds to ionizing irradiation-induced DNA double-strand breaks. Heavy ions from an accelerated carbon ion beam have been used to cure cancer because they are more effective than ionizing irradiation such as X-ray and γ-radiation in terms of biological damage. In a previous study, we demonstrated that a persimmon leaf flavonol (PLF) promoted the cytotoxic effect of chemotherapeutic agents on cancer cells through inhibition of checkpoint activities, especially in the ATM dependent pathway. The present study investigated whether PLF inhibits checkpoint activity during the DNA damage response induced by heavy ion irradiation. Treatment with PLF significantly increased the cytotoxicity of heavy ion irradiation in A549 adenocarcinoma cells. The phosphorylation of checkpoint proteins such as p53, SMC1, and Chk1 was increased by heavy ions. PLF reduced the phosphorylation of checkpoint proteins. Pre-treatment with PLF significantly prevented the decrease of mitotic cells in heavy ion-exposed cells. We further evaluated tumor volume in SCID mice inoculated with human lung adenocarcinoma A549 cells. The combination treatment of PLF and heavy ion resulted in a decrease of tumor volume compared with controls, although PLF itself did not exhibit any effect. These results indicate that PLF inhibits tumor growth through modulation of the DNA damage response. PLF may be useful for clinical application in combination with heavy ion radiotherapy.

关键词： DNA Damage Checkpoint Persimmon Leaf Flavonols Heavy Ion Irradiation Xenograft

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单细胞凝胶电泳技术检测小鼠成纤维细胞DNA的氧化损伤及修复

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西安交通大学学报（医学版） 2007年第1期28卷 25-27页

作者：陈忻西田浩志小西徹也首都医科大学中医药学院北京100069 日本新泻药科大学

目的观察小鼠成纤维细胞由过氧化氢(H2O2)引起的DNA损伤及其修复,并详细介绍单细胞凝胶电泳技术。方法培养NIH3T3细胞,H2O2造成细胞氧化损伤,单细胞凝胶电泳技术(SCGE,Comet Assay)检测细胞DNA的损伤情况。结果①建立了H2O2致NIH3T3细胞... 详细信息

目的观察小鼠成纤维细胞由过氧化氢(H2O2)引起的DNA损伤及其修复,并详细介绍单细胞凝胶电泳技术。方法培养NIH3T3细胞,H2O2造成细胞氧化损伤,单细胞凝胶电泳技术(SCGE,Comet Assay)检测细胞DNA的损伤情况。结果①建立了H2O2致NIH3T3细胞DNA损伤的分级图谱;②H2O2引起的小鼠成纤维细胞DNA单链断裂与H2O2的浓度呈依赖性关系;③细胞在除去H2O2后15 min已出现明显修复,多数修复可在1 h内完成,但少数修复可能需要较长时间才能完成。结论单细胞凝胶电泳技术是一种简便、敏感的检测DNA氧化损伤的方法。

关键词：单细胞凝胶电泳 DNA单链断裂 DNA氧化损伤 DNA修复

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Inferior outcomes of liver transplantation for hepatocellular carcinoma during early-COVID-19 pandemic in the United States

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World Journal of Hepatology 2023年第4期15卷 554-563页

作者： Inkyu S Lee Kenji Okumura Ryosuke Misawa hiroshi Sogawa Gregory Veillette Devon John Thomas Diflo Seigo nishida Abhay Dhand Department of Surgery Westchester Medical CenterValhallaNY 10595United States Department of Medicine Westchester Medical CenterValhallaNY 10595United States

BACKGROUND Early in the coronavirus disease 2019(COVID-19)pandemic,there was a significant impact on routine medical care in the United States,including in fields of transplantation and *** To analyze the impact and outcomes of early COVID-19 pandemic on liver transplantation(LT)for hepatocellular carcinoma(HCC)in the United *** WHO declared COVID-19 as a pandemic on March 11,*** retrospectively analyzed data from the United Network for Organ Sharing(UNOS)database regarding adult LT with confirmed HCC on explant in 2019 and *** defined pre-COVID period from March 11 to September 11,2019,and early-COVID period as from March 11 to September 11,*** Overall,23.5%fewer LT for HCC were performed during the COVID period(518 vs 675,P<0.05).This decrease was most pronounced in the months of March-April 2020 with a rebound in numbers seen from May-July *** LT recipients for HCC,concurrent diagnosis of non-alcoholic steatohepatitis significantly increased(23 vs 16%)and alcoholic liver disease(ALD)significantly decreased(18 vs 22%)during the COVID *** age,gender,BMI,and MELD score were statistically similar between two groups,while waiting list time decreased during the COVID period(279 days vs 300 days,P=0.041).Among pathological characteristics of HCC,vascular invasion was more prominent during COVID period(P<0.01),while other features were the *** the donor age and other characteristics remained same,the distance between donor and recipient hospitals was significantly increased(P<0.01)and donor risk index was significantly higher(1.68 vs 1.59,P<0.01)during COVID *** outcomes,90-day overall and graft survival were the same,but 180-day overall and graft were significantly inferior during COVID period(94.7 vs 97.0%,P=0.048).On multivariable Coxhazard regression analysis,COVID period emerged as a significant risk factor of post-transplant mortality(Hazard ratio 1.85;95%CI:1.28-2.68,P=0.001).CONCLUSION Durin

关键词： Liver transplantation Hepatocellular carcinoma COVID-19 Mortality Graft failure United Network for Organ Sharing database

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Trends and outcomes of liver transplantation among older recipients in the United States

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World Journal of Transplantation 2022年第8期12卷 259-267页

作者： Kenji Okumura Joon Sub Lee Abhay Dhand hiroshi Sogawa Gregory Veillette Devon John Ryosuke Misawa Roxana Bodin David C Wolf Thomas Diflo Seigo nishida Department of Surgery Westchester Medical Center/New York Medical CollegeValhallaNY 10595United States

BACKGROUND The average age of recipients and donors of liver transplantation(LT)is *** there has been a change in the indications for LT over the years,data regarding the trends and outcomes of LT in the older population is *** To assess the clinical characteristics,age-related trends,and outcomes of LT among the older population in the United *** We analyzed data from the United Network for Organ Sharing database between *** sample was split into younger group(18-64 years old)and older group(≥65 years old).RESULTS Between 1987-2019,155758 LT were performed in the United *** this period there was a rise in median age of the recipients and percentage of LT recipients who were older than 65 years increased(P<0.05)with the highest incidence of LT among older population seen in 2019(1920,23%).Common primary etiologies of liver disease leading to LT in older patients when compared to the younger group,were non-alcoholic steatohepatitis(16.4%vs 5.9%),hepatocellular carcinoma(14.9%vs 6.9%),acute liver failure(2.5%vs 5.2%),hepatitis C cirrhosis(HCV)(19.2%vs 25.6%)and acute alcoholic hepatitis(0.13%vs 0.35%).In older recipient group female sex and Asian race were higher,while model for end-stage liver disease(MELD)score and rates of preoperative mechanical ventilation were lower(P<0.01).Median age of donor,female sex,body mass index(BMI),donor HCV positive status,and donor risk index(DRI)were significantly higher in older group(P<0.01).In univariable analysis,there was no difference in post-transplant length of hospitalization,one-year,three-year and five-year graft survivals between the two *** multivariable Cox-Hazard regression analysis,older group had an increased risk of graft failure during the five-year post-transplant period(hazard ratio:1.27,P<0.001).Other risk factors for graft failure among recipients were male sex,African American race,re-transplantation,presence of diabetes,mechanical ventilation at th

关键词： Liver transplant Elderly Outcomes Hepatocellular carcinoma Nonalcohol steatohepatitis

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Efficacy of an orally active small-molecule inhibitor of RANKL in bone metastasis

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Bone Research 2019年第1期7卷 66-75页

作者： Yuta Nakai Kazuo Okamoto Asuka Terashima Shogo Ehata Jun nishida Takeshi Imamura Takashi Ono hiroshi Takayanagi Department of Immunology Graduate School of Medicine and Faculty of MedicineThe University of TokyoHongo 7-3-1Bunkyo-kuTokyoJapan Department of Orthodontic Science Graduate School of Medical and Dental SciencesTokyo Medical and Dental UniversityYushima 1-5-45Bunkyo-kuTokyoJapan Department of Osteoimmunology Graduate School of Medicine and Faculty of MedicineThe University of TokyoHongo 7-3-1Bunkyo-kuTokyoJapan Department of Molecular Pathology Graduate School of MedicineThe University of TokyoHongo 7-3-1Bunkyo-kuTokyoJapan Department of Molecular Medicine for Pathogenesis Ehime University Graduate School of MedicineShitsukawaToonEhimeJapan

Bone is one of the preferred sites for the metastasis of malignant tumours,such as breast cancer,lung cancer and malignant *** cells colonizing bone have the capacity to induce the expression of receptor activator of nuclear factor-κB ligand(RANKL),which promotes osteoclast differentiation and ***-induced osteoclastic bone resorption leads to a vicious cycle between tumours and bone cells that fuels osteolytic tumour growth,causing bone pain and ***,RANKL contributes to bone metastasis by acting as a chemoattractant to bone for tumour cells that express its receptor,*** inhibition of the RANKL–RANK pathway is a promising treatment for bone metastasis,and a human monoclonal anti-RANKL antibody,denosumab,has been used in the ***,orally available drugs targeting RANKL must be developed to increase the therapeutic benefits to *** we report the efficacy of the small-molecule RANKL inhibitor AS2676293 in treating bone metastasis using mouse *** administration of AS2676293 markedly inhibited bone metastasis of human breast cancer cells MDA-MB-231-5a-D-Luc2 as well as tumour-induced ***2676293 suppressed RANKLmediated tumour migration in the transwell assay and inhibited bone metastasis of the murine cell line B16F10,which is known not to trigger osteoclast *** on the results from this study,RANKL inhibition with a small-molecule compound constitutes a promising therapeutic strategy for treating bone metastasis by inhibiting both osteoclastic bone resorption and tumour migration to bone.

关键词： Bone tumours metastasis

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Risk factors for local recurrence and appropriate surveillance interval after endoscopic resection

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World Journal of Gastroenterology 2019年第12期25卷 1502-1512页

作者： Yoriaki Komeda Tomohiro Watanabe Toshiharu Sakurai Masashi Kono Kazuki Okamoto Tomoyuki Nagai Mamoru Takenaka Satoru Hagiwara Shigenaga Matsui Naoshi nishida Naoko Tsuji hiroshi Kashida Masatoshi Kudo Department of Gastroenterology and Hepatology Kindai University Faculty of Medicine

BACKGROUND Risk factors for local recurrence after polypectomy, endoscopic mucosal resection(EMR), and endoscopic submucosal dissection(ESD) have not been ***, the appropriate interval for endoscopic surveillance of colorectal tumors at high-risk of local recurrence has not been *** To clarify the clinicopathological characteristics of recurrent lesions after endoscopic colorectal tumor resection and determine the appropriate *** Three hundred and sixty patients(1412 colorectal tumors) who underwent polypectomy, EMR, or ESD and received endoscopic surveillance subsequently for more than one year to detect local recurrence were enrolled in this study. The clinicopathological factors associated with local recurrence were determined via univariate and multivariate *** Local recurrence was observed in 31 of 360(8.6%) patients [31 of 1412(2.2%)lesions] after colorectal tumor resection. Piecemeal resection, tumor size of more than 2 cm, and the presence of villous components were associated with colorectal tumor recurrence after endoscopic resection. Of these three factors, the piecemeal resection procedure was identified as an independent risk factor for recurrence. Colorectal tumors resected into more than five pieces were associated with a high risk of recurrence since the average period from resection torecurrence in these cases was approximately 3 mo. The period to recurrence in cases resected into more than 5 pieces was much shorter than that in those resected into less than 4 pieces(3.8 ± 1.9 mo vs 7.9 ± 5.0 mo, P < 0.05).CONCLUSION Local recurrence of endoscopically treated colorectal tumors depends upon the outcome of first endoscopic procedure. Piecemeal resection was the only significant risk factor associated with local recurrence after endoscopic resection.

关键词： Local recurrence Colorectal tumor Endoscopic surveillance Piecemeal resection Risk factors

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Optical Sum Frequency Generation Spectroscopy of Cracked Non-Glutinous Rice (Oryza sativa L.) Kernels

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Journal of Biomaterials and Nanobiotechnology 2016年第1期7卷 13-18页

作者： Wataru Kouyama Takahiro nishida Khuat Thi Thu Hien Goro Mizutani hiroshi Hasegawa Hiroaki Miyamura School of Materials Science Japan Advanced Institute of Science and Technology Nomi Japan School of Environmental Science University of Shiga Prefecture Hikone Japan Shiga Prefecture Agricultural Technology Promotion Center Omihachiman Japan

In order to study the correlation between the cracking of rice (Oryza sativa L.) kernels and the molecular structure of the amylopectin in them, we attempted optical sum frequency generation (SFG) spectroscopy in the C-H stretching vibration region for normal and cracked japonica non-glutinous rice kernels. The samples were Koshihikari and Nipponbare. In Nipponbare, the width of the SFG spectrum peak at 2915 cm- 1 of the cracked rice kernels was broader than that of the normal ones, while for Koshihikari there was no clear difference. The width of the 2915 cm- 1 peak is suggested to originate from the variety of the higher-order structure of the saccharide chains in amylopectin. Although this is a tentative result, this method is shown to have a potential of serving for preventing the cracking of the rice kernels.

关键词： Rice Kernels Cracking in Hot Weather Optical Sum Frequency Generation (SFG) Amylopectin Non-Glutinous Rice

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The Interactive Effect of Soy Isoflavones with Docosahexaenoic Acid on Intelligence among the Middle-Aged and Elderly Japanese

The Interactive Effect of Soy Isoflavones with Docosahexaeno...

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The 8th Asia/Oceania Regional Congress of Gerontology and Geriatrics

作者： Fujiko Ando Yukiko nishida Tomoko Imai Chikako Tange Yasuyuki Fukukawa hiroshi Shimokata National Institute for Longevity Sciences National Center for Geriatrics and Gerontology National Institute for Longevity Sciences National Center for Geriatrics and Gerontology National Institute for Longevity Sciences National Center for Geriatrics and Gerontology National Institute for Longevity Sciences National Center for Geriatrics and Gerontology Seitoku University National Institute for Longevity Sciences National Center for Geriatrics and Gerontology

＜正＞Purpose:Docosahexaenoic acid（DHA）,one of polyunsaturated fatty acid derived mainly from fish oil plays an important role for neuronal ***,it is chemically unstable and easily *** isoflavones may enhance the ef...

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Intraductal neoplasm of the intrahepatic bile duct: Clinicopathological study of 24 cases

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World Journal of Gastroenterology 2012年第28期18卷 3673-3680页

作者： Yoshiki Naito Hironori Kusano Osamu Nakashima Eiji Sadashima Satoshi Hattori Tomoki Taira Akihiko Kawahara Yoshinobu Okabe Kazuhide Shimamatsu Jun Taguchi Seiya Momosaki Koji Irie Rin Yamaguchi hiroshi Yokomizo Michiko Nagamine Seiji Fukuda Shinichi Sugiyama Naoyo nishida Koichi Higaki Munehiro Yoshitomi Masafumi Yasunaga Koji Okuda Hisafumi Kinoshita Masayoshi Kage Masamichi Nakayama Makiko Yasumoto Jun Akiba Hirohisa Yano Departments of Pathology Kurume University School of Medicine Kurume 830-0011 Japan Biostatistics Center Kurume University Kurume 830-0011 Japan Department of Diagnostic Pathology Kurume University Hospital Kurume 830-0011 Japan Division of Gastroenterology Department of Medicine Kurume University School of Medicine Kurume 830-0011 Japan Department of Pathology Omuta City General Hospital Omuta 836-8567 Japan Department of Pathology Asakura Medical Association Hospital Fukuoka 838-0069 Japan Department of Pathology National Hospital Organization Kyushu Medical Center Fukuoka 810-8563 Japan Department of Pathology Shin-Koga Hospital Tenjinkai 120 Tenjincho Kurume 830-0033 Japan Department of Pathology Kurume University Medical Center 155-1 Kokubumachi Kurume 839-0863 Japan Department of Surgery Japanese Red Cross Kumamoto Hospital Kumamoto 861-8520 Japan Department of Pathology Japanese Red Cross Kumamoto Hospital Kumamoto 861-8520 Japan Division of Surgery Saiseikai Kumamoto Hospital Kumamoto 861-4193 Japan Department of Pathology St Mary's Hospital Kurume 830-8543 Japan Department of Surgery Kurume University School of Medicine Kurume 830-0011 Japan

AIM: To investigate the clinicopathological features of intraductal neoplasm of the intrahepatic bile duct (INihB). METHODS: Clinicopathological features of 24 cases of INihB, which were previously diagnosed as biliary papillomatosis or intraductal growth of intrahepatic biliary neoplasm, were reviewed. Mucin immunohistochemistry was performed for mucin (MUC)1, MUC2, MUC5AC and MUC6. Ki-67, P53 and β-catenin immunoreactivity were also examined. We categorized each tumor as adenoma (low grade), borderline (intermediate grade), and malignant (carcinoma in situ , high grade including tumors with microinvasion). RESULTS: Among 24 cases of INihB, we identified 24 tumors. Twenty of 24 tumors (83%) were composed of a papillary structure; the same feature observed in intraductal papillary neoplasm of the bile duct (IPNB). In contrast, the remaining four tumors (17%) showed both tubular and papillary structures. In three of the four tumors (75%), macroscopic mucin secretion was limited but microscopic intracellular mucin was evident. Histologically, 16 tumors (67%) were malignant, three (12%) were borderline, and five (21%) were adenoma. Microinvasion was found in four cases (17%). Immunohistochemical analysis revealed that MUC1 was not expressed in the borderline/adenoma group but was expressed only in malignant lesions (P = 0.0095). Ki-67 labeling index (LI) was significantly higher in the malignant group than in the borderline/adenoma group (22.2 ± 15.5 vs 7.5 ± 6.3, P < 0.01). In the 16 malignant cases, expression of MUC5AC showed borderline significant association with high Ki-67 LI (P = 0.0622). Nuclear expression of β-catenin was observed in two (8%) of the 24 tumors, and these two tumors also showed MUC1 expression. P53 was negative in all tumors. CONCLUSION: Some cases of INihB have a tubular structure, and are subcategorized as IPNB with tubular structure. MUC1 expression in INihB correlates positively with degree of malignancy.

关键词：胆管肿瘤临床病理管内免疫组织化学方法恶性肿瘤管状结构乳头状瘤肝

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Castor oil as booster for colon capsule endoscopy preparation reduction: A prospective pilot study and patient questionnaire

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World Journal of Gastrointestinal Pharmacology and Therapeutics 2021年第4期12卷 79-89页

作者： Kota Takashima Yoriaki Komeda Toshiharu Sakurai Sho Masaki Tomoyuki Nagai Shigenaga Matsui Satoru Hagiwara Mamoru Takenaka Naoshi nishida hiroshi Kashida Konosuke Nakaji Tomohiro Watanabe Masatoshi Kudo Department of Gastroenterology and Hepatology Kindai University Faculty of MedicineOsaka 589-8511Japan Division of Gastroenterology Department of Internal MedicineEndoscopy CenterAishinkai Nakae HospitalWakayama-Shi 640-8461Japan

BACKGROUND Preparation for colon capsule endoscopy(CCE)requires a large liquid laxative volume for capsule excretion,which compromises the procedure's *** To assess the safety and utility of castor oil-boosted bowel *** This prospective cohort study including 20 patients(age range,16-80 years;six men and 14 women)suspected of having colorectal disease was conducted at Kindai University Hospital from September 2017 to August *** patients underwent CCE because of the following inclusion criteria:previous incomplete colonoscopy in other facility(n=20),history of abdominal surgery(n=7),or organ abnormalities such as multiple diverticulum(n=4)and adhesion after surgery(n=6).The exclusion criteria were as follows:Dysphagia,history of allergic reactions to the drugs used in this study(magnesium citrate,polyethylene glycol,metoclopramide,and castor oil),possibility of pregnancy,possibility of bowel obstruction or stenosis based on symptoms,or scheduled magnetic resonance imaging within 2 wk after *** primary outcome was the capsule excretion rate within the battery life,as evaluated by the total large bowel observation rate,large bowel transit time,and bowel creasing level using a fivegrade scale in different colorectal *** secondary outcomes were complications,colorectal lesion detection rates,and patients’*** The castor oil-based regimen was implemented in 17 *** patients cancelled CCE because they could tolerate castor oil,but not liquid *** capsule excretion rate within the battery life was 88%(15/17).The mean large bowel transit time was 236 *** 70%of patients had satisfactory colon cleansing *** detected colon polyps(14/17,82%)and colonic diverticulum(4/12,33%).The sensitivity,specificity,and diagnostic accuracy rates for detecting colorectal polyps(size≥6 mm)were 76.9%,75.0%,and 76.4%,*** sensitivity,specificity,and diagnostic accuracy rates for dete

关键词： Bowel preparation regimen Castor oil Colon capsule endoscopy Colonoscopy Colorectal diseases Prospective study

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