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Management of metastatic esophagogastric junction adenocarcinoma

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Journal of Cancer Metastasis and Treatment 2018年第1期4卷 290-299页

作者： Tasuku Toihata yu imamura Masayuki Watanabe Hideo Baba Department of Gastroenterological Surgery Graduate School of Medical ScienceKumamoto UniversityKumamoto 860-0811Japan Gastroenterological Surgery Cancer Institute HospitalTokyo 135-8550Japan

The prognosis of metastatic disease of esophagogastric junction adenocarcinoma remains poor,despite using a variety of regimens using cytotoxic *** understanding of molecular characteristic and tumor microenvironment of this cancer is currently instigating new therapeutic *** this review,we summarized previous evidences of cytotoxic agents widely used worldwide,and updated recent developments of molecular targeted drugs,and immune checkpoint inhibitors.

关键词： Esophagogastric junction adenocarcinoma advanced molecular targeted drug immune checkpoint inhibitor immunotherapy

Overview of genetic and epigenetic alterations in the pathogenesis of esophagogastric junctional adenocarcinoma and esophageal adenocarcinoma: recent fi ndings by next generation sequencing

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Journal of Cancer Metastasis and Treatment 2015年第1期1卷 123-129页

作者： yu imamura Ryuma Tokunaga Kenichi Nakamura Hideo Baba Masayuki Watanabe Department of Gastroenterological Surgery Cancer Institute Hospital of Japanese Foundation for Cancer ResearchTokyo 135-8550Japan Department of Gastroenterological Surgery Graduate School of Medical SciencesKumamoto UniversityKumamoto 860-8555Japan.

Esophagogastric junctional adenocarcinoma is commonly treated as esophageal adenocarcinoma(EAC)and has dramatically increased in Western countries for several *** similar trend has been observed in Asian countries(not in China).Barrett’s esophagus(BE)is a widely accepted precursor of *** advances of next-generation sequencing could provide researchers with a better understanding of genetic and epigenetic alterations in the carcinogenesis of *** this review,we have summarized the recently reported major genetic and epigenetic alterations in both BE and *** hedgehog/bone morphogenetic protein axis,which is a key signaling for esophageal development,plays an important role in BE intestinal *** nucleotide polymorphisms related to esophageal organogenesis,such as FOXF1 and FOXP3,are frequently detected in BE *** the progression of BE to adenocarcinoma,lacking of normal function of TP53 and CDKN2A by loss of heterozygosity(LOH),mutation,or promoter methylation has been frequently *** at 9p(coding CDKN2A)is an earlier event to EAC carcinogenesis compared to that at 17q(coding TP53)*** order to further elucidate the pathogenesis of BE and EAC,it will be necessary to analyze these genetic/epigenetic alterations in combination with clinical data in a large-scale cohort.

关键词： Barrett’s esophagus carcinogenesis epigenetic esophageal adenocarcinoma esophagogastric junctional adenocarcinoma genetic intestinal metaplasia

Nutrient-regulated dynamics of chondroprogenitors in the postnatal murine growth plate

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Bone Research 2023年第2期11卷 340-353页

作者： Takeshi Oichi Joe Kodama Kimberly Wilson Hongying Tian yuka imamura Kawasawa yu Usami Yasushi Oshima Taku Saito Sakae Tanaka Masahiro Iwamoto Satoru Otsuru Motomi Enomoto-Iwamoto Department of Orthopedics School of MedicineUniversity of MarylandBaltimoreMD21201USA Sensory&Motor System Medicine Faculty of MedicineThe University of TokyoBunkyo-kuTokyo1138655Japan Department of Orthopedics Teikyo University School of MedicineTokyo1738608Japan Department of Biochemistry and Molecular Biology Pennsylvania State University College of MedicineHersheyPA17033USA Department of Oral Pathology Osaka University Graduate School of DentistrySuitaOsaka5650871Japan

Longitudinal bone growth relies on endochondral ossification in the cartilaginous growth plate,where chondrocytes accumulate and synthesize the matrix scaffold that is replaced by *** chondroprogenitors in the resting zone maintain the continuous turnover of chondrocytes in the growth *** is a leading cause of growth retardation in children;however,after recovery from nutrient deprivation,bone growth is accelerated beyond the normal rate,a phenomenon termed catch-up *** nutritional status is a known regulator of long bone growth,it is largely unknown whether and how chondroprogenitor cells respond to deviations in nutrient ***,using fate-mapping analysis in Axin2CreERT2 mice,we showed that dietary restriction increased the number of Axin2+chondroprogenitors in the resting zone and simultaneously inhibited their *** nutrient deficiency was resolved,the accumulated chondroprogenitor cells immediately restarted differentiation and formed chondrocyte columns,contributing to accelerated ***,we showed that nutrient deprivation reduced the level of phosphorylated Akt in the resting zone and that exogenous IGF-1 restored the phosphorylated Akt level and stimulated differentiation of the pooled chondroprogenitors,decreasing their *** study of Axin2CreERT2 revealed that nutrient availability regulates the balance between accumulation and differentiation of chondroprogenitors in the growth plate and further demonstrated that IGF-1 partially mediates this regulation by promoting the committed differentiation of chondroprogenitor cells.

关键词： progenitor plate maintain

Tumor-derived insulin-like growth factor-binding protein-1 contributes to resistance of hepatocellular carcinoma to tyrosine kinase inhibitors

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Cancer Communications 2023年第4期43卷 415-434页

作者： Hiroyuki Suzuki Hideki Iwamoto Takahiro Seki Toru Nakamura Atsutaka Masuda Takahiko Sakaue Toshimitsu Tanaka Yasuko imamura Takashi Niizeki Masahito Nakano Shigeo Shimose Tomotake Shirono yu Noda Naoki Kamachi Miwa Sakai Kazutoyo Morita Masamichi Nakayama Tomoharu Yoshizumi Ryoko Kuromatsu Hirohisa Yano Yihai Cao Hironori Koga Takuji Torimura Division of Gastroenterology Department of MedicineKurume University School of MedicineKurume CityFukuokaJapan Liver Cancer Research Division Research Center for Innovative Cancer TherapyKurume UniversityKurume CityFukuokaJapan Iwamoto Internal Medicine Clinic Kitakyushu CityFukuokaJapan Department of Microbiology Tumor and Cell biologyKarolinska InstitutetStockholmSweden Department of Surgery and Science Graduate School of Medical ScienceKyushu UniversityFukuoka CityFukuokaJapan Department of Pathology Kurume University School of MedicineKurume CityFukuokaJapan

Background:Antiangiogenic tyrosine kinase inhibitors(TKIs)provide one of the few therapeutic options for effective treatment of hepatocellular carcinoma(HCC).However,patients with HCC often develop resistance toward antiangiogenic TKIs,and the underlying mechanisms are not *** aim of this study was to determine the mechanisms underlying antiangiogenic TKI resistance in ***:We used an unbiased proteomic approach to define proteins that were responsible for the resistance to antiangiogenic TKIs in HCC *** evaluated the prognosis,therapeutic response,and serum insulin-like growth factor-binding protein-1(IGFBP-1)levels of 31 lenvatinib-treated HCC *** on the array of results,a retrospective clinical study and preclinical experiments using mouse and human hepatoma cells were ***,in vivo genetic and pharmacological gain-and loss-of-function experiments were ***:In the patient cohort,IGFBP-1 was identified as the signaling molecule with the highest expression that was inversely associated with overall ***,antiangiogenic TKI treatment markedly elevated tumor IGFBP-1 levels via the hypoxia-hypoxia inducible factor ***-1 stimulated angiogenesis through activation of the integrinα5β1-focal adhesion kinase ***,loss of IGFBP-1 and integrinα5β1 by genetic and pharmacological approaches re-sensitized HCC to lenvatinib ***:Together,our data shed light onmechanisms underlying acquired resistance of HCC to antiangiogenic *** TKIs induced an increase of tumor IGFBP-1,which promoted angiogenesis through activating the IGFBP-1-integrinα5β1 *** data bolster the application of a new therapeutic concept by combining antiangiogenic TKIs with IGFBP-1 inhibitors.

关键词： hepatocellular carcinoma hypoxia IGFBP-1 lenvatinib molecular targeting resistance tyrosine kinase inhibitors

Multicenter study of endoscopic preoperative biliary drainage for malignant distal biliary obstruction

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World Journal of Gastroenterology 2016年第14期22卷 3793-3802页

作者： Naoki Sasahira Tsuyoshi Hamada Osamu Togawa Ryuichi Yamamoto Tomohisa Iwai Kiichi Tamada Yoshiaki Kawaguchi Kenji Shimura Takero Koike yu Yoshida Kazuya Sugimori Shomei Ryozawa Toshiharu Kakimoto Ko Nishikawa Katsuya Kitamura Tsunao imamura Masafumi Mizuide Nobuo Toda Iruru Maetani yuji Sakai Takao Itoi Masatsugu Nagahama Yousuke Nakai Hiroyuki Isayama Department of Gastroenterology JCHO Tokyo Takanawa HospitalTokyo 108-8606Japan Department of Gastroenterology Graduate School of MedicineThe University of TokyoTokyo 113-8655Japan Department of Gastroenterology Saitama International Medical CenterSaitama Medical UniversitySaitama 350-1298Japan Department of Gastroenterology and Hepatology Saitama Medical University International Medical CenterSaitama 350-8550Japan Department of Gastroenterology Kitasato UniversityKanagawa 252-0375Japan Department of Gastroenterology Jichi Medical UniversityTochigi 329-0498Japan Department of Gastroenterology Tokai UniversityKanagawa 259-1193Japan Department of Gastroenterology Asahi General HospitalChiba 289-2511Japan Department of Internal Medicine Japanese Red Cross Ashikaga HospitalTochigi 326-0843Japan Department of Gastroenterology Kimitsu Central HospitalChiba 292-8535Japan Department of Gastroenterology Yokohama City University Medical CenterKanagawa 232-0024Japan Department of Gastroenterology Showa University Northern Yokohama HospitalKanagawa 242-0032Japan Department of Gastroenterology Saitama City HospitalSaitama 336-8522Japan Department of Gastroenterology Ageo Central General HospitalSaitama 362-8588Japan Division of Gastroenterology Department of MedicineShowa University School of MedicineTokyo 142-8666Japan Department of Gastroenterology Toranomon HospitalTokyo 105-0001Japan Department of Gastroenterology Gunma UniversityGunma 371-0034Japan Department of Gastroenterology Mitsui Memorial HospitalTokyo 101-8643Japan Division of Gastroenterology and Hepatology Department of Internal MedicineToho University Ohashi Medical CenterTokyo 153-0044Japan Department of Gastroenterology Chiba UniversityChiba 260-0856Japan Department of Gastroenterology Tokyo Medical UniversityTokyo 160-0023Japan Department of Gastroenterology Showa University Fujigaoka HospitalKanagawa 227-8501Japan

AIM: To determine the optimal method of endoscopic preoperative biliary drainage for malignant distal biliary ***: Multicenter retrospective study was conducted in patients who underwent plastic stent (PS) or nasobiliary catheter (NBC) placement for resectable malignant distal biliary obstruction followed by surgery between January 2010 and March 2012. Procedure-related adverse events, stent/catheter dysfunction (occlusion or migration of PS/NBC, development of cholangitis, or other conditions that required repeat endoscopic biliary intervention), and jaundice resolution (bilirubin level < 3.0 mg/dL) were evaluated. Cumulative incidence of jaundice resolution and dysfunction of PS/NBC were estimated using competing risk analysis. Patient characteristics and preoperative biliary drainage were also evaluated for association with the time to jaundice resolution and PS/NBC dysfunction using competing risk regression ***: In total, 419 patients were included in the study (PS, 253 and NBC, 166). Primary cancers included pancreatic cancer in 194 patients (46%), bile duct cancer in 172 (41%), gallbladder cancer in three (1%), and ampullary cancer in 50 (12%). The median serum total bilirubin was 7.8 mg/dL and 324 patients (77%) had ≥ 3.0 mg/dL. During the median time to surgery of 29 d [interquartile range (IQR), 30-39 d]. PS/NBC dysfunction rate was 35% for PS and 18% for NBC [Subdistribution hazard ratio (SHR) = 4.76; 95%CI: 2.44-10.0, P < 0.001]; the pig-tailed tip was a risk factor for PS dysfunction. Jaundice resolution was achieved in 85% of patients and did not depend on the drainage method (PS or NBC).CONCLUSION: PS has insufficient patency for preoperative biliary drainage. Given the drawbacks of external drainage via NBC, an alternative method of internal drainage should be explored.

关键词： Endoscopic preoperative biliary drainage Malignant distal biliary obstruction Periampullary cancer Plastic stent Nasobiliary drainage

未冻水含量对含废弃轮胎碎屑冻土超声波速度的影响

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岩土工程学报 2000年第6期22卷 716-719页

作者：盛煜福田正己金学三今村辙中科院寒区旱区环境与工程研究所冻土工程国家重点实验室甘肃兰州730000 日本北海道大学低温科学研究所日本通商省计量研究所

本文介绍了用液浸式超声波循环法测定冻土中超声波速度的原理和过程 ,并在 - 0 .2℃～ - 1 0℃温度范围内测定了含有不同比例废弃轮胎碎屑的Tomakomai粉土的纵、横波速度。结果表明超声波在冻土中的纵、横波传播速度在冻土温度接近 0℃... 详细信息

本文介绍了用液浸式超声波循环法测定冻土中超声波速度的原理和过程 ,并在 - 0 .2℃～ - 1 0℃温度范围内测定了含有不同比例废弃轮胎碎屑的Tomakomai粉土的纵、横波速度。结果表明超声波在冻土中的纵、横波传播速度在冻土温度接近 0℃时随温度的升高而急剧降低。结合冻土的未冻水含量随温度的变化规律分析表明 ,冻土中超声波的传播速度与冻土未冻水含量呈良好的线形关系 ,且未冻水含量每增加 1 % ,纵波速度约降低 6 2m/s;横波速度降低约 35m/s。

关键词：冻土超声波速度未冻水含量废弃轮胎碎屑

Prion Protein Binds to Aldolase A Produced by Bovine Intestinal M Cells

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Open Journal of Veterinary Medicine 2015年第3期5卷 43-60页

作者： yuya Nagasawa yu Takahashi Wataru Itani Hitoshi Watanabe yusuke Hidaka Shotaro Morita Kei Suzuki Kouichi Watanabe Shyuichi Ohwada Haruki Kitazawa Morikazu imamura Takashi Yokoyama Motohiro Horiuchi Suehiro Sakaguchi Shirou Mohri Michael T. Rose Tomonori Nochi Hisashi Aso Cellular Biology Laboratory Tohoku University Sendai Japan Food Immunology Group Tohoku University Sendai Japan Prion Disease Research Center National Institute of Animal Health Tsukuba Japan Laboratory of Veterinary Hygiene Hokkaido University Sapporo Japan Institute for Enzyme Research The University of Tokushima Tokushima Japan Institute of Biological Environmental and Rural Sciences Aberystwyth University Aberystwyth UK

Microfold (M) cells are a kind of intestinal epithelial cell in the follicle-associated epithelium (FAE) of Peyer’s patches. They can transport antigens and microorganisms to lymphoid tissues. Bovine spongiform encephalopathy (BSE) is a fatal neurodegenerative disorder in cattle. It is linked to variant Creutzfeldt-Jakob disease in humans. Although it is thought that M cells transport the BSE agent, the exact mechanism by which it crosses the intestinal barrier is not clear. We have bovine intestinal epithelial cell line (BIE cells), which can differentiate into the M cell type in vitro after stimulation, and which is able to transport the BSE agent. We show here that M cells are able to incorporate large numbers of PrP coated magnetic particles into intracellular vesicles, which we collected. The results of 2-DE show a specific protein associated with the PrP-coated particles, compared with non-coated particles. This protein was identified as aldolase A, a glycolytic pathway enzyme, using LC-MS/MS analysis. Aldolase A was synthesized and secreted by BIE cells, and increased during M cell differentiation. In the villi of the bovine intestine, aldolase A was detected on the surface of the epithelium and in the mucus droplet of goblet cells. In the FAE of bovine jejunal and ileal Peyer’s patches, aldolase A was localized on the surface and the apical part of the M cells. The binding of rbPrP to aldolase A was clearly detected and inhibited by pre-treatment of anti-aldolase A antibody. Aldolase A was co-stained with incorporated PrPSc in M-BIE cells. These results suggest that bovine M cells and goblet cells synthesize aldolase A, and that aldolase A may have the ability to bind PrP and associate with PrP in cellular vesicles. Therefore, aldolase A-positive M cells may play a key role in the invasion of BSE into the body.

关键词： Peyer’s Patch M Cell BIE Cells Aldolase A PrP Binding Protein