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Bioactive Materials 2024年第5期35卷 291-305页

作者： Shuoji Zhu Junfeng Xuan Yunchao Shentu Katsuhiko Kida Masaki kobayashi Wei Wang Minoru Ono Dehua Chang Department of Cardiac Surgery University of TokyoTokyo113-8655Japan Department of Cell Therapy in Regenerative Medicine University of Tokyo HospitalTokyo113-8655Japan Nissan Chemical Corporation Tokyo103-0027Japan Winhealth Pharma 999077Hong Kong

Mesenchymal stem cell(MSC)transplantation has been explored for the clinical treatment of various ***,the current two-dimensional(2D)culture method lacks a natural spatial microenvironment in *** limitation restricts the stable establishment and adaptive maintenance of MSC *** natural polymers with biocompatibility for constructing stereoscopic MSC microenvironments may have significant application *** study used chitin-based nanoscaffolds to establish a novel MSC three-dimensional(3D)*** compared 2D and 3D cultured human umbilical cord-derived MSCs(UCMSCs),including dif-ferentiation assays,cell markers,proliferation,and *** UCMSCs are in 3D culture,they can differentiate into bone,cartilage,and *** 3D culture condition,cell proliferation is enhanced,accompanied by an elevation in the secretion of paracrine factors,including vascular endothelial growth factor(VEGF),hepa-tocyte growth factor(HGF),Interleukin-6(IL-6),and Interleukin-8(IL-8)by ***,a 3D culture environment promotes angiogenesis and duct formation with HUVECs(Human Umbilical Vein Endothelial Cells),showing greater luminal area,total length,and branching points of tubule formation than a 2D *** cultured in a 3D environment exhibit enhanced undifferentiated,as well as higher cell activity,making them a promising candidate for regenerative medicine and therapeutic applications.

关键词： Cellhesion®chitin nanoscaffolds Mesenchymal stem cells Stemness 3D culture

α-fetoprotein,vascular endothelial growth factor receptor-1 and early recurrence of hepatoma

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World Journal of Gastroenterology 2012年第4期18卷 340-348页

作者： Toshiya Kamiyama Masato Takahashi Kazuaki Nakanishi Hideki Yokoo Hirofumi Kamachi Nozomi kobayashi Michitaka Ozaki Satoru Todo Department of General Surgery Graduate School of MedicineHokkaido University Department of Transplantation Surgery Graduate School of MedicineHokkaido University Department of Molecular Surgery Graduate School of MedicineHokkaido University

AIM:To investigate whether α-fetoprotein (AFP) and vascular endothelial growth factor receptor (VEGFR)-1 correlate with early recurrence of hepatoma/hepatocel-lular carcinoma (HCC).METHODS:From 2000 to 2005,114 consecutive pa-tients with HCC underwent primary curative *** mean age was 60.7 (8.7) years and 94 patients were *** median follow-up period was 71.2 mo (range:43-100 mo).Immediately prior to commencing laparotomy,5 mL bone marrow was aspirated from thesternum and collected in citrate-coated test *** initial 2 mL of bone marrow aspirate was discarded in each *** mRNA and VEGFR-1 mRNA in the bone marrow and peripheral blood (BM-and PH-AFP mRNA and BM-and PH-VEGFR-1 mRNA,respectively) were measured by real-time quantitative reverse transcription polymerase chain *** normal controls,VEGFR-1 mRNA in the bone marrow and peripheral blood was also measured in 11 living liver *** data were evaluated for any correlation with early recurrence,comparing clinical and pathological ***:The cut-off value of the BM-AFP mRNA and PH-AFP mRNA level in patients with HCC was set at 1.92 × 10-7 and zero,respectively,based on data from the controls.A total of 34 (29.8%) and six (5.4%) patients were positive for BM-AFP mRNA and PH-AFP mRNA,*** BM-VEGFR-1 mRNA levels in all HCC patients were higher than those in the normal con-trols,and this was the case also for *** 25-percentile values for the BM-and PH-VEGFR-1 mRNA in HCC patients were used as the cut-off values for assigning the patients into two groups based on these transcript *** High group for BM-VEG-FR-1 mRNA contained 81 (71.1%) HCC cases and the Low group was assigned 33 (28.9%) *** numbers for PH-VEGFR-1mRNA were 78 (75.0%) and 26 (25.0%),*** recurred in 80 patients;in the remnant liver in 48 cases,in the remnant liver and remote tissue in 20,and in the remote tissue alone in ***-AFP mRNA-positive cases

关键词： α-fetoprotein Vascular endothelial growth factor receptor-i mRNA Early recurrence Hepatocellular carcinoma

Upregulation of epidermal growth factor receptor 4 in oral leukoplakia

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International Journal of Oral Science 2013年第1期5卷 14-20页

作者： Hiroshi kobayashi Kenichi Kumagai Akito Gotoh Takanori Eguchi Hiroyuki Yamada Yoshiki Hamada Satsuki Suzuki Ryuji Suzuki Department of Oral and Maxillofacial Surgery Tsurumi University Department of Rheumatology and Clinical Immunology Clinical Research Center for Rheumatology and AllergySagamihara National HospitalNational Hospital Organization Section of Biological Science Research Center for Odontology Nippon Dental University School of Dentistry

In the present study,we investigate the expression profile of the epidermal growth factor receptor family,which comprises EGFR/ ErbBl,HER2/ErbB2,HER3/ErbB3 and HER4/ErbB4 in oral leukoplakia(LP).The expression of four epidermal growth factor receptor (EGFR) family genes and their ligands were measured in LP tissues from 14 patients and compared with levels in 10 patients with oral lichen planus(OLP) and normal oral mucosa(NOM) from 14 healthy donors by real-time polymerase chain reaction(PCR) and *** mRNA coexpression of ErbBl,ErbB2,ErbB3and ErbB4 was detected in LP *** of the receptors,only ErbB4 mRNA and protein was more highly expressed in LP compared with NOM *** were strongly expressed by epithelial keratinocytes in LP lesions,as shown by *** the ligands,the mRNA of Neuregulin2 and 4 were more highly expressed in OLP compared with NOM ***,enhanced ErbB4 on the keratinocytes and synchronous modulation of EGFR family genes may contribute to the pathogenesis and carcinogenesis of LP.

关键词： epidermal growth factor receptor immunohistochemistry oral leukoplakia quantitative real-time polymerase chain reaction

Need for pancreatic stenting after sphincterotomy in patients with difficult cannulation

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World Journal of Gastroenterology 2014年第26期20卷 8617-8623页

作者： Kazunari Nakahara Chiaki Okuse Keigo Suetani Yosuke Michikawa Shinjiro kobayashi Takehito Otsubo Fumio Itoh Department of Gastroenterology and Hepatology St. Marianna University School of Medicine Department of Gastroenterological and General Surgery St. Marianna University School of Medicine

AIM: To investigate the need for pancreatic stenting after endoscopic sphincterotomy (EST) in patients with difficult biliary cannulation.

关键词： Pancreatic stenting Pancreatic guidewire placement Post-endoscopic retrograde cholangiopancreatography pancreatitis Endoscopic sphincterotomy Endoscopic retrograde cholangiopancreatography

STI571 (Glivec) suppresses the expression of vascular endothelial growth factor in the gastrointestinal stromal tumor cell line,GIST-T1

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World Journal of Gastroenterology 2006年第5期12卷 703-708页

作者： Toufeng Jin Hajime Nakatani Takahiro Taguchi Takumi Nakano Takehiro Okabayashi Takeki Sugimoto Michiya kobayashi Keijiro Araki Department of Tumor Surgery Kochi Medical School Kochi University Nankoku Kochi 783-8505 Japan and Department of General Surgery College of Medical Yanbian University 119 Juzijie Yanji Jilin Province China Department of Tumor Surgery Kochi-Medical School Kochi University Nankoku Kochi 783-8505 Japan Department of Human Health and Medical Science Graduate school of Kuroshio Science Kochi UniversityNankoku Kochi 783-8503 Japan

AIM： To estimate whether S-TI571 inhibits the expression of vascular endothelial growth factor （VEGF） in the gastrointestinal stromal tumor （GIST） cells. METHODS： We used GIST cell line, GIST-T1. It has a heterogenic 57-bp deletion in exon 11 to produce a mutated c-KIT, which results in constitutive activation of c-KIT. Cells were treated with/without STI571 or stem cell factor （SCF）. Transcription and expression of VEGF were determined by RT-PCR and flow cytometry or Western blotting, respectively. Activated c-KIT was estimated by immunoprecipitation analysis. Cell viability was determined by PITT assay. RESULTS： Activation of c-KIT was inhibited by STI571 treatment. VEGF was suppressed at both the transcriptional and translational levels in a temporal and dose-dependent manner by STI571. SCF upregulated the expression of VEGF and it was inhibited by S-13571. STI571 also reduced the cell viability of the GIST-T1 cells, as determined by PTT assay. CONCLUSION： Activation of c-KIT in the GIST-T1 regulated the expression of VEGF and it was inhibited by ST571. STI571 has antitumor effects on the GIST cells with respect to not only the inhibition of cell growth, but also the suppression of VEGF expression.

关键词： c-KIT Vascular endothelial growth factor(VEGF) S-13571 Gastrointestinal stromal tumor GIST-T1

Protective effects of oral glutathione on fasting-induced intestinal atrophy through oxidative stress

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World Journal of Gastroenterology 2017年第36期23卷 6650-6664页

作者： Hiroyuki Uchida Yukari Nakajima Kazuo Ohtake Junta Ito Masahiko Morita Ayako Kamimura Jun kobayashi Division of Pathophysiology Department of Clinical Dietetics and Human NutritionFaculty of Pharmaceutical ScienceJosai University Kyowa Hakko Bio Co. Ltd.Healthcare Products Development Center

AIM To determine whether oral glutathione(GSH)administration can alleviate the effects of fasting-induced intestinal atrophy in the small intestinal mucosa. METHODS Rats were divided into eight *** group was fed ad libitum,another was fed ad libitum and received oral GSH,and six groups were administrated saline(SA)or GSH orally during *** height,apoptosis,and cell proliferation in the jejunum were histologically evaluated.i NOS protein expression(by immunohistochemistry),nitrite levels(by high performance liquid chromatography,as a measure of NO production),8-hydroxydeoxyguanosine formation(by ELISA,indicating ROS levels),glutathione/oxidized glutathione(GSH/GSSG)ratio(by enzymatic colorimetric detection),andγ-glutamyl transpeptidase(Ggt1)mR NA levels in the jejunum(by semi-quantitative RT-PCR)were also estimated. RESULTS O r a l G S H a d m i n i s t r a t i o n w a s d e m o n s t r a t e d t o drastically reduce fasting-induced intestinal atrophy in the *** particular,jejunal mucosal height was enhanced in GSH-treated animals compared to SA-treated animals[527.2±6.9 for 50 mg/kg GSH,567.6±5.4 for 500 mg/kg GSH vs 483.1±4.9(μm),P<0.01at 72 h].This effect was consistent with decreasing changes in GSH-treated animals compared to SA-treated animals for iN OS protein staining[0.337±0.016for 50 mg/kg GSH,0.317±0.017 for 500 mg/kg GSH vs 0.430±0.023(area of staining part/area of tissue),P<0.01 at 72 h]and NO[2.99±0.29 for 50 mg/kg GSH,2.88±0.19 for 500 mg/kg GSH vs 5.34±0.35(nmol/g tissue),P<0.01 at 72 h]and ROS[3.92±0.46for 50 mg/kg GSH,4.58±0.29 for 500 mg/kg GSH vs6.42±0.52(8-OHdG pg/μg DNA),P<0.01,P<0.05at 72 h,respectively]levels as apoptosis mediators in the ***,oral GSH administration attenuated cell proliferation decreases in the fasting jejunum[182.5±1.9 for 500 mg/kg GSH vs 155.8±3.4(5-Brd U positive cells/10 crypts),P<0.01 at 72h].Notably,both GSH concentration and Ggt1 m RNA expression in the jejunum were also attenu

关键词： Intestinal atrophy Glutathione Apoptosis Cell proliferation Inducible nitric oxide synthase

Clinical and computed tomography findings of appendiceal diverticulitis vs acute appendicitis

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World Journal of Gastroenterology 2015年第13期21卷 3921-3927页

作者： Daisuke Ito Kenji Miki Shimizu Seiichiro Shojiro Hata Kaoru kobayashi Masanori Teruya Michio Kaminishi Department of Gastro- intestinal Surgery Showa General HospitalTokyo 187--8510Japan Department of Pathology Showa General HospitalTokyo 187-8510Japan

AIM: To study the clinical features and computed tomography(CT) findings of appendiceal diverticulitis vs acute ***: We retrospectively reviewed the records of 451 patients who had undergone appendectomy inour in stitution from January 2007 to September 2012. Patient demographics, clinical features, pathological findings, and surgical outcomes were analyzed. We also compared preoperative CT images of 25 patients with appendiceal diverticulitis with those of 25 patients with acute ***: Among 451 patients, 44(9.7%) were diagnosed to have appendiceal diverticulitis and 398(86.9%) to have acute appendicitis. Patients with appendiceal diverticulitis were older(59 vs 37 years, P < 0.001) and had a longer duration of the illness(4.0 d vs 1.0 d, P < 0.001). Perforation rates in patients with appendiceal diverticulitis were higher(68% vs 27%, P < 0.001). The appendix could be visualized in only 13 patients(52%) among the appendiceal diverticulitis cases, but in all acute appendicitis cases. CT findings suggestive of appendiceal diverticulitis included the absence of fluid collection in the appendix(84% vs 12%, P < 0.001), absence of appendicolith(92% vs 52%, P = 0.005), and formation of abscess(68% vs 16%, P < 0.001). Appendiceal diverticula were identified in 6 patients(24%).CONCLUSION: Among patients who had undergone appendectomy, 9.7% had appendiceal diverticulitis. Patients with appendiceal diverticulitis had different clinical features and CT findings from patients with acute appendicitis.

关键词： Appendiceal diverticulitis Acute appendicitis Comp

Hydrogen promotes the activation of Cu, Zn superoxide dismutase in a rat corneal alkali-burn model

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International Journal of Ophthalmology(English edition) 2020年第8期13卷 1173-1179页

作者： Takeshi Arima Tsutomu Igarashi Masaaki Uchiyama Maika kobayashi Ikuroh Ohsawa Akira Shimizu Hiroshi Takahashi Department of Ophthalmology Nippon Medical SchoolTokyo1138602Japan Department of Analytic Human Pathology Nippon Medical SchoolTokyo1138602Japan Biological Process of Aging Tokyo Metropolitan Institute of GerontologyTokyo173-0015Japan

AIM: To investigate the effects of hydrogen(H2) on Cu, Zn superoxide dismutase(SOD1) activation in a rat model of corneal alkali burn. METHODS: In each rat, one cornea was subjected to alkali exposure. Physiological saline(saline group) or H2-dissolved saline(H2 group) was instilled continuously on the cornea for 5 min before and after alkali exposure. Inflammatory cells, neovascularization, and cytoplasmic SOD1 levels were evaluated immunohistochemically in enucleated eyes from both groups. Three-dimensional ultrastructural tissue changes in the eyes were analyzed using low-vacuum scanning electron ***: The numbers of both inflammatory and vascular endothelial cells were significantly reduced in the corneas of the H2 group(P<0.01). Furthermore, H2 treatment increased both cytoplasmic SOD1 levels(P<0.01) and activity in corneal epithelial cells(P<0.01). Notably, the SOD1 activity level in the H2 group was approximately 2.5-fold greater than that in the saline ***: H2 treatment suppresses inflammation and neovascularization in the injured cornea and indirectly suppresses oxidative insult to the cornea by upregulating the SOD1 enzyme protein level and activity.

关键词： hydrogen alkali burn Cu,Zn superoxide dismutase low-vacuum scanning electron microscopy rats

Oval mucosal opening bloc biopsy after incision and widening by ring thread traction for submucosal tumor

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World Journal of Gastroenterology 2017年第39期23卷 7185-7190页

作者： Hirohito Mori Hideki Kobara Yu Guan Yasuhiro Goda Nobuya kobayashi Noriko Nishiyama Tsutomu Masaki Department of Gastroenterology and Neurology Kagawa University Departments of Pharmacology Kagawa University

Gastric submucosal tumors(SMTs) less than 2 cm are generally considered benign neoplasms, and endoscopic observation is recommended, but SMTs over 2 cm, 40% of which are gastrointestinal stromal tumors(GISTs), have malignant potential. Although the Japanese Guidelines for GIST recommend partial surgical resection for GIST over 2 cm with malignant potential as well as en bloc large tissue sample to obtain appropriate and large specimens of SMTs, several reports have been published on tissue sampling of SMTs, such as with endoscopic ultrasound sound fine needle aspiration, submucosal tunneling bloc biopsy, and the combination of bite biopsy and endoscopic mucosal resection. Because a simpler, more accurate method is needed for appropriate treatment, we developed oval mucosal opening bloc biopsy after incision and widening by ring thread traction for submucosal tumor(OMOB) approach. OMOB was simple and enabled us to obtain large samples under direct procedure view as well as allowed us to restore to original mucosa.

关键词： Gastric submucosal tumors Gastrointestinal stromal tumor Reversible opening biopsy Endoscopic ultrasonography Large sample

Delayed immune-related sclerosing cholangitis after discontinuation of pembrolizumab:A case report

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World Journal of Gastroenterology 2022年第28期28卷 3732-3738页

作者： Takeshi Tanaka Arata Sakai Masahiro Tsujimae Yasutaka Yamada Takashi kobayashi Atsuhiro Masuda Yuzo Kodama Division of Gastroenterology Department of Internal MedicineKobe University Graduate School of MedicineKobe 650-0017HyogoJapan

BACKGROUND Secondary sclerosing cholangitis,characterized by biliary obstruction,can be caused by drugs such as immune checkpoint inhibitors(ICIs).While there a few reports of sclerosing cholangitis after immune checkpoint inhibitor administration,no case has been reported after discontinuation of such *** SUMMARY A 68-year-old man who underwent chemotherapy for lung adenocarcinoma with bone metastasis presented with abdominal pain and fever 4 mo after the final administration of *** tomography revealed thickening of the gallbladder wall and dilatation of the common bile *** retrograde cholangiopancreatography revealed an irregularly narrowed intrahepatic bile *** of the bile duct demonstrated that CD8+T cells were predominant over CD4+T *** biopsy showed dominant infiltration of CD8+T in the portal tract,but onion-skin lesions were not *** patient was diagnosed with immune-related sclerosing cholangitis induced by *** of methylprednisolone and endoscopic nasobiliary drainage were performed,but the cholangiography and laboratory test findings did not *** further treatment was administered due to disease progression,and the patient was referred for palliative *** Immune-related sclerosing cholangitis may have a late onset,and such cases occurring after discontinuation of ICIs should be carefully managed.

关键词： Immune-related adverse events Sclerosing cholangitis Delayed immunerelated events Case report