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Cancer-associated fibroblast-derived secreted phosphoprotein 1 contributes to resistance of hepatocellular carcinoma to sorafenib and lenvatinib

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Cancer Communications 2023年第4期43卷 455-479页

作者： JungWoo Eun Jung Hwan Yoon Hye Ri Ahn Seokhwi Kim young Bae Kim Su Bin Lim Won Park TaeWook Kang Geum Ok Baek Moon Gyeong Yoon Ju A Son Ji HyangWeon Soon Sun Kim Hyo Jung Cho jae youn Cheong Department of Gastroenterology Ajou University School of MedicineSuwonSouth Korea Department of Pathology College of MedicineThe Catholic University of KoreaSeoulSouth Korea Department of Biomedical Sciences AjouUniversity Graduate School of MedicineSuwonSouth Korea Department of Pathology Ajou University School of MedicineSuwonSouth Korea Department of Biochemistry&Molecular Biology Ajou University School of MedicineSuwonSouth Korea The Moagen IncDaejeonSouth Korea

Background:Cancer-associated fibroblasts(CAFs)play an important role in the induction of *** study aimed to clarify the mechanism underlying CAF-mediated resistance to two tyrosine kinase inhibitors(TKIs),sorafenib and lenvatinib,and to identify a novel therapeutic target for overcoming TKI resistance in hepatocellular carcinoma(HCC).Methods:We performed a systematic integrative analysis of publicly available gene expression datasets and whole-transcriptome sequencing data from 9 pairs of CAFs and para-cancer fibroblasts isolated from human HCC and para-tumor tissues,respectively,to identify key molecules that might induce resistance to *** then performed in vitro and in vivo experiments to validate selected targets and related *** associations of plasma secreted phosphoprotein 1(SPP1)expression levels before sorafenib/lenvatinib treatment with progression-free survival(PFS)and overall survival(OS)of 54 patients with advanced HCC were evaluated using Kaplan-Meier and Cox regression ***:Bioinformatic analysis identified CAF-derived SPP1 as a candidate molecule driving TKI ***1 inhibitors reversed CAF-induced TKI resistance in vitro and in ***-derived SPP1 activated rapidly accelerated fibrosarcoma(RAF)/mitogen-activated protein kinase(MAPK)and phosphatidylinositol 3-kinase(PI3K)/protein kinase B(AKT)/mammalian target of rapamycin(mTOR)through the integrin-protein kinase C-alpha(PKCα)signaling pathway and promoted epithelial-to-mesenchymal transition(EMT).A high plasma SPP1 level before TKI treatment was identified as an independent predictor of poor PFS(P=0.026)and OS(P=0.047)in patients with advanced HCC after TKI ***:CAF-derived SPP1 enhances TKI resistance in HCC via bypass activation of oncogenic signals and EMT *** inhibition represents a promising therapeutic strategy against TKI resistance ***,plasma SPP1 level before TKI treatment represents a potential biomar

关键词： drug resistance epithelial-to-mesenchymal transition hepatocellular carcinoma secreted phosphoprotein 1

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Sinkihwan-gamibang ameliorates puromycin aminonucleoside-induced nephrotic syndrome

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Chinese Journal of Natural Medicines 2022年第03期 177-184页

作者： Lee Hyeon Kyoung Jang youn jae Na Se Won Kim Hye Yoom Han Byung Hyuk Lee Yun Jung Lee Ho Sub Yoon Jung Joo Kang Dae Gill Hanbang Cardio-Renal Syndrome Research Center Wonkwang University College of Oriental Medicine and Professional Graduate School of Oriental Medicine Wonkwang University

Nephrotic syndrome（NS） is a kidney disease characterized by hypertriglyceridemia, massive proteinuria, hypo-albuminemia and peripheral edema. Sinkihwan-gamibang（SKHGMB） was recorded in a traditional Chinese medical book named“Bangyakhappyeon（方藥合編）” and its three prescriptions Sinkihwan, Geumgwe-sinkihwan, and Jesaeng-sinkihwan belong to Gamibang. This study confirmed the effect of SKHGMB on renal dysfunction in an NS model induced by puromycin aminonucleoside（PAN）. The experimental NS model was induced in male Sprague Dawley（SD） rats through injection of PAN(50 mg·kg-1) via the femoral vein. SKHGMB not only reduced the size of the kidneys increased due to PAN-induced NS, but also decreased proteinuria and ascites. In addition, SKHGMB significantly ameliorated creatinine clearance, creatinine, and blood urea nitrogen. SKHGMB relieved glomeruli dilation and tubules fibrosis in the glomeruli of the NS model. SKHGMB inhibited the protein and mRNA levels of the NLRP3 inflammasome including NLRP3, ASC, and pro-caspase-1 in NS rats. SKHGMB reduced the protein and mRNA levels of fibrosis regulators in NS rats. The results indicated that SKHGMB exerts protective effects against renal dysfunction by inhibiting of renal inflammation and fibrosis in NS rats.

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Optimal culture conditions for the generation of natural killer cell-induced dendritic cells for cancer immunotherapy

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Cellular & Molecular Immunology 2012年第1期9卷 45-53页

作者： Thanh-Nhan Nguyen-Pham Deok-Hwan Yang Truc-Anh Thi Nguyen Mi-Seon Lim Cheol Yi Hong Mi-Hyun Kim Hyun Ju Lee youn-Kyung Lee Duck Cho Soo-young Bae jae-Sook Ahn Yeo-Kyeoung Kim Ik-Joo Chung Hyeoung-Joon Kim Je-Jung Lee Research Center for Cancer Immunotherapy Chonnam National University Hwasun HospitalJeollanamdoKorea Department of Hematology-Oncology Chonnam National University Hwasun HospitalJeollanamdoKorea Vaxcell-Bio Therapeutics JeollanamdoKorea The Brain Korea 21 Project Center for Biomedical Human Resources at Chonnam National UniversityGwangjuKorea

Dendritic cell(DC)-based vaccines continue to be considered an attractive tool for cancer *** require an additional signal from the environment or other immune cells to polarize the development of immune responses toward T helper 1(Th1)or Th2 *** play a role in natural killer(NK)cell activation,and NK cells are also able to activate and induce the maturation of *** investigated the types of NK cells that can induce the maturation and enhanced function of DCs and the conditions under which these interactions *** that were activated by resting NK cells in the presence of inflammatory cytokines exhibited increased expression of several costimulatory molecules and an enhanced ability to produce *** cell-stimulated DCs potently induced Th1 polarization and exhibited the ability to generate tumor antigen-specific cytotoxic T lymphocyte *** data demonstrate that functional DCs can be generated by coculturing immature DCs with freshly isolated resting NK cells in the presence of Toll-like receptor agonists and proinflammatory cytokines and that the resulting DCs effectively present antigens to induce tumor-specific T-cell responses,which suggests that these cells may be useful for cancer immunotherapy.

关键词： cancer immunotherapy dendritic cells natural killer cells signal

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Oxyntic gland adenoma endoscopically mimicking a gastric neuroendocrine tumor: A case report

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World Journal of Gastroenterology 2015年第16期21卷 5099-5104页

作者： Tae-In Lee jae-young Jang Seungmin Kim Jung-Wook Kim young-Woon Chang youn-Wha Kim Division of Gastroenterology Department of Internal MedicineCollege of MedicineKyung Hee University Department of Pathology College of MedicineKyung Hee University

Gastric adenocarcinoma is one of the most common malignancies *** and immunohistologic analyses classify the phenotypes of gastric adenocarcinoma into several groups based on the variable clinical and pathologic features.A new and rare variant of gastric adenocarcinoma with chief cell differentiation(GA-CCD)has recently been *** reporting the distinct clinicopathologic characteristics proposed the term oxyntic gland polyp/adenoma because of the benign nature of the ***,GA-CCD is a solitary mucosal lesion that develops either in the gastric cardia or ***,this lesion is characterized by tightly clustered glands and anastomosing cords of chief ***,GA-CCD is diffusely positive for mucin(MUC)6 and negative for MUC2and ***,other gastric tumors such as a gastric neuroendocrine tumor or fundic gland polyp have been difficult to *** GA-CCD tends to be endoscopically misdiagnosed as a neuroendocrine tumor or fundic gland polyp,comprehensive assessment and observation by an endoscopist are strongly ***,we report a rare case of oxyntic gland adenoma endoscopically mimicking a gastric neuroendocrine tumor that was successfully removed by endoscopic mucosal resection.

关键词： Chief cell differentiation Gastric carcinoma Mucin 6 Neuroendocrine tumor Oxyntic gland adenoma

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Type I and II interferons enhance dendritic cell maturation and migration capacity by regulating CD38 and CD74 that have synergistic effects with TLR agonists

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Cellular & Molecular Immunology 2011年第4期8卷 341-347页

作者： Thanh-Nhan Nguyen-Pham Mi-Seon Lim Truc Anh Thi Nguyen youn-Kyung Lee Chun-Ji Jin Hyun Ju Lee Cheol Yi Hong jae-Sook Ahn Deok-Hwan Yang Yeo-Kyeoung Kim Ik-Joo Chung Byoung Chul Park Hyeoung-Joon Kim Je-Jung Lee Research Center for Cancer Immunotherapy Chonnam National University Hwasun HospitalJeollanamdoKorea Department of Hematology-Oncology Chonnam National UniversityGwangjuKorea The Brain Korea 21 Project Center for Biomedical Human Resources at Chonnam National UniversityGwangjuKorea Vaxcell-Bio Therapeutics JeollanamdoKorea Korea Research Institute of Bioscience and Biotechnology(KRIBB) DaejeonKorea

The major limitation for the maturation of dendritic cells(DCs)using Toll-like receptor(TLR)agonists is their decreased ability to migrate into lymph nodes compared with conventional ***38 can be used as a multifunctional marker to modulate migration,survival and Th1 responses of ***74 has been shown to negatively regulate DC *** goal of this study was to investigate the combinations of TLR agonists and interferons(IFNs)that most effectively regulate CD38 and CD74 expression on *** TLR agonist stimulation in combination with IFN-a and IFN-c was the best method for regulating CD38 and CD74 expression and inducing the highest secretion of *** in vitro migration assay showed that DCs treated with this combination had significantly enhanced migratory ability,similar to that observed in cells expressing CD38,CD74 and *** results of this study suggest that an alternative maturation protocol in which two TLR ligands are combined with type I and II IFNs generates potent DCs that have both a high migratory capacity and high IL-12p70 production.

关键词： CD38 CD74 dendritic cells interferon Toll-like receptor

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The current status of hormone treatment for prostate cancer patients in Korean real-world practice:a multi-institutional observational study

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Asian Journal of Andrology 2019年第2期21卷 115-120页

作者： Jung Kwon Kim Jung Jun Kim Taek Won Gang Tae Kyun Kwon Hong Sup Kim Seung Chui Park jae-Shin Park Jong-Yeon Park Seok Joong Yoon youn-Soo Jeon Jin Seon Cho Kwan Joong Joo Sung-Hoo Hong Seok-Soo Byun the Korean Urological Oncology Society Department of Urology Seoul National University Bundang HospitalSeongnam 13620Korea Department of Urology Hallym University Sacred Heart HospitalAnyang 14068Korea Department of Urology Kangbuk Samsung HospitalSeoul 03181Korea Department of Urology Seoul St.Mary HospitalSeoul 06591Korea 不详 Department of Urology Chonnam National University HospitalGwangju 61469Korea School of Medicine Kyungpook National University Medical CenterDaegu 41404Korea Department of Urology Konkuk University Medical CenterSeoul 05080Korea Department of Urology Wonkwang University HospitalIksan 54538Korea Department of Urology Daegu Catholic University Medical CenterDaegu 41911Korea Department of Urology Ulsan UniversityGangneung Asan HospitalGangneung 25440Korea Department of Urology Chungbuk National University HospitalCheongju 28644Korea Department of Urology Soonchunhyang University HospitalCheonan 31151Korea

We aimed to evaluate the current nationwide trend,efficacy,safety,and quality of life(QoL)profiles of hormone treatment in real-world practice settings for prostate cancer(PCa)patients in Korea.A total of 292 men with any biopsy-proven PCa(TanyNanyMany)from 12 institutions in Korea were included in this multi-institutional,observational study of prospectively collected *** luteinizing hormone-releasing hormone(LHRH)agonists were allowed to be investigational *** was defined as(1)the rate of castration(serum testosterone≤50 ng dl^-1)at 4-week visit and(2)breakthrough(serum testosterone>50 ng dl^-1 after castration).Safety assessments included routine examinations for potential adverse events,laboratory tests,blood pressure,body weight,and bone min era I density(BMD,at baseli ne and at the last follow-up visit).QoL was assessed using the Expa nded Prostate Cancer Index Composite-26(EPIC-26).The most comm on initial therapeutic regimen was LHRH agonist with an ti-androge n(78.0%),and the most commonly used LHRH agonist for combination and mono therapy was leuprolide(64.0%for combi natio n and 58.0%for monotherapy).The castration and breakthrough rates were 78.4%and 6.6%,*** laboratory results related to dyslipidemia worsened after 4 weeks of hormone *** addition,the mean BMD T-score was significantly lower at the last follow-up(mean:-1.950)compared to baseline(mean:-0.195).The mean total EPIC-26 score decreased from 84.8(standard deviation[s.d.]:12.2)to 78.3(s.d.:8.1),with significant deterioration only in the urinary domain(mean:23.5 at baseli ne and 21.9 at the 4-week visit).These findi ngs dem on strate the n ationwide trend of current practice setti ngs in hormone treatment for PCa in Korea.

关键词： efficacy hormonal treatment Korean population prostate cancer safety trend

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道路两边不同距离内哺乳动物丰富度的差异(英文)

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兽类学报 2003年第3期23卷 193-197页

作者： Shin-jae RHIM Wee-Haeng HUR young-Su PARK Seo-youn CHOI Chang-Bae LEE 朴仁珠 Woo-Shin LEE Department of Forest Resources Seoul NationalUniversity 黑龙江省林业科学院

为更好地保护和管理部分哺乳类动物及其栖息地 ,自 2 0 0 1年 6月至 2 0 0 2年 3月在韩国白头大干山脉 8个被道路切割的林区内调查了道路两边一定距离内所见哺乳动物随距离增加而变化的丰富度。我们共调查了 10种哺乳类 (野猪、狍、獐... 详细信息

为更好地保护和管理部分哺乳类动物及其栖息地 ,自 2 0 0 1年 6月至 2 0 0 2年 3月在韩国白头大干山脉 8个被道路切割的林区内调查了道路两边一定距离内所见哺乳动物随距离增加而变化的丰富度。我们共调查了 10种哺乳类 (野猪、狍、獐、黄鼬、貉、豹猫、华南兔、松鼠、花鼠、鼹 )的各种痕迹 (粪便、足迹、食痕、卧迹及休息处 ) ,发现距道路近处两边的丰富度确有较大下降。这说明道路建设的确影响哺乳类的生境选择及其利用方式。所以今后在道路设计、管理及扩充等方面均需充分考虑和满足所有野生动物整个生命过程所需的空间要求。

关键词：道路两边距离哺乳动物丰富度栖息地痕迹韩国

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Simple colonoscopy reporting system checking the detection rate of colon polyps

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World Journal of Gastroenterology 2015年第31期21卷 9380-9386页

作者： jae Hyun Kim youn Jung Choi Hye Jung Kwon Seun Ja Park Moo In Park Won Moon Sung Eun Kim Department of Internal Medicine Kosin University College of Medicine

AIM: To present a simple colonoscopy reporting system that can be checked easily the detection rate of colon ***: A simple colonoscopy reporting system Kosin Gastroenterology(KG quality reporting system) was developed. The polyp detection rate(PDR),adenoma detection rate(ADR),serrated polyp detection rate(SDR),and advanced adenoma detection rate(AADR) are easily calculated to use this ***: In our gastroenterology center,the PDR,ADR,SDR,and AADR test results from each gastroenterologist were updated,every month. Between June 2014,when the program was started,and December 2014,the overall PDR and ADR in our center were 62.5% and 41.4%,respectively. And the overall SDR and AADR were 7.5% and 12.1%,***: We envision that KG quality reporting system can be applied to develop a comprehensive system to check colon polyp detection rates in other gastroenterology centers.

关键词： Colon polyp Detection rate Reporting system

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横流式水轮机下游悬臂梁对微能量采集性能的影响（英文）

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风机技术 2019年第4期61卷 25-29,I0008页

作者： Hyeon-jae Noh Cheng Tang youn-Jea Kim Graduate School of Mechanical Engineering Sungkyunkwan University

横流式水轮机在叶轮处将势能转化为动能,与此同时会在转轮尾流中引发一种称为涡激振动(VIV)的流动现象。横流式水轮机的VIV是一种由绕虚拟涡轴线的流动所诱发的非定常流动现象。这种振动可以作为一种压电能量的采集来源。本文采用商用CF... 详细信息

横流式水轮机在叶轮处将势能转化为动能,与此同时会在转轮尾流中引发一种称为涡激振动(VIV)的流动现象。横流式水轮机的VIV是一种由绕虚拟涡轴线的流动所诱发的非定常流动现象。这种振动可以作为一种压电能量的采集来源。本文采用商用CFD软件ANSYS CFX 17.1对横流式水轮机进行了数值分析,考察其微能量采集的性能(MEH)。在研究过程中,于横流式水轮机下游布置了悬臂梁,并考察了悬臂梁间距对微能量采集性能的影响。本文给出了不同流动和几何条件下的速度矢量和涡流强度分布图。

关键词：能量采集横流式几何条件悬臂梁速度矢量涡流强度涡激振动分布图

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Recurrent gastric neuroendocrine tumors treated with total gastrectomy

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World Journal of Gastroenterology 2015年第46期21卷 13195-13200页

作者： Myounghwa Jung Jung-Wook Kim jae-young Jang young Woon Chang Sun Hee Park Yong Ho Kim youn Wha Kim Department of Internal Medicine College of MedicineKyung Hee University Department of Surgery College of MedicineKyung Hee University Department of Pathology College of MedicineKyung Hee University

Gastric neuroendocrine tumors are rare; however,the incidence has recently increased due to the increasing use of upper endoscopy. Neuroendocrine tumors arise from the excess proliferation of enterochromaffinlike(ECL) cells. The proliferative changes of enterochromaffin cells evolve through a hyperplasiadysplasia-neoplasia sequence that is believed to underlie the pathogenesis of gastric neuroendocrine tumors. Endoscopic resection is recommended as the initial treatment if the tumor is not in an advanced stage. However,there is no definite guideline for the treatment of recurrent gastric neuroendocrine tumors following endoscopic resection. Here,we report a rare case of gastric neuroendocrine tumors in a 56-yearold male who experienced two recurrences within 11 years after endoscopic resection. The patient finally underwent a total gastrectomy. The pathological features of the resected stomach exhibited the full hyperplasia-dysplasia-neoplasia sequence of the ECL cells in a single specimen.

关键词： Neuroendocrine tumor Hyperplasia of neuroendocrine

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