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The predictability of T3 disease in staging MRI following prostate biopsy decreases in patients with high initial PSA and Gleason score

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Asian Journal of Andrology 2011年第3期13卷 487-493,515页

作者： Young Hwii Ko Deuk Jae Sung Sung Gu kang Seok Ho kang Jeong Gu Lee Je jong Kim Jun Cheon Department of Urology Korea University School of Medicine Seoul Korea Department of Radiology Korea University School of Medicine Seoul Korea

To obtain improved accuracy in predicting extracapsular extension （ECE） and seminal vesicle invasion （SVI）, we evaluated the variables affecting the predictability of staging magnetic resonance imaging （MRI, phased-array coil） and estimated their impact on accuracy between preoperative MRI staging and histological outcome. A total of 121 patients with localized or locally advanced prostate cancer who underwent robotic radical prostatectomy （RALP） were included. Following transrectal biopsy, all enrolled patients had undergone MRI for staging work-up. After RALP, only 43.8% （53/121） of the patients were matched with the MRI predicted stage. Compared to the matched group in the prediction of ECE, the unmatched group had significantly higher initial prostate-specific antigen （PSA, 12.8 ng m1-1 versus 8.1 ng m1-1, P=0.048）. In the prediction of SVI, initial PSA （8.1 ng ml- 1 versus 17.3 ng ml- 1, P=0.009） and biopsy Gleason score （6.5 versus 7.6, P=0.035） were significantly higher in the unmatched group. When applying clinical cutoffs of initial PSA of 10 and 20 ng ml-1, the accuracy of MRI in the prediction of ECE was decreased in the group with PSA over 20 ng ml- 1 （75.6, 64.5 and 37.5%, P=0.01）, and this group had significantly decreased accuracy of MRI in the prediction of SVI （91.5, 77.4 and 37.5%, P〈0.01）. Applying the clinical cutoff of a Gleason score of 7, the accuracy of MRI in the prediction of SVI was decreased in the higher G leason score group （93.9, 82.1 and 62.9%, P= 0.01）. Thus, for these patient groups, to obtain margin negativity during radical prostatectomy, operative findings, rather than post-biopsy MRI images, may provide substantial information, implying a clinical advantage in conducting MRI before prostate biopsy.

关键词： magnetic resonance imaging neoplasm staging prostatic neoplasms

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Impacts of Nutlin-3a and exercise on murine double minute 2-enriched glioma treatment

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Neural Regeneration Research 2025年第4期20卷 1135-1152页

作者： Yisheng Chen Zhongcheng Fan Zhiwen Luo Xueran kang Renwen Wan Fangqi Li Weiwei Lin Zhihua Han Beijie Qi Jinrong Lin Yaying Sun Jiebin Huang Yuzhen Xu Shiyi Chen Department of Sport Medicine Huashan HospitalFudan UniversityShanghaiChina Department of Orthopedic Surgery Hainan Province Clinical Medical CenterHaikou Affiliated Hospital of Central South University Xiangya School of MedicineHaikouHainan ProvinceChina Department of Basic Medicine Shanghai Jiao Tong University School of MedicineShanghai Jiao Tong UniversityShanghaiChina Department of Neurosurgery Second Affiliated Hospital of Zhejiang University School of MedicineZhejiang UniversityHangzhouZhejiang ProvinceChina Department of Orthopedics Shanghai General HospitalSchool of Medicine Shanghai Jiao Tong UniversityShanghaiChina Department of Infectious Diseases Children’s Hospital of Fudan UniversityNational Children’s Medical CenterShanghaiChina Department of Rehabilitation The Second Affiliated Hospital of Shandong First Medical UniversityTaianShandong ProvinceChina

Recent research has demonstrated the impact of physical activity on the prognosis of glioma patients,with evidence suggesting exercise may reduce mortality risks and aid neural *** role of the small ubiquitin-like modifier(SUMO)protein,especially post-exercise,in cancer progression,is gaining attention,as are the potential anti-cancer effects of *** used machine learning to create the exercise and SUMO-related gene signature(ESLRS).This signature shows how physical activity might help improve the outlook for low-grade glioma and other *** demonstrated the prognostic and immunotherapeutic significance of ESLRS markers,specifically highlighting how murine double minute 2(MDM2),a component of the ESLRS,can be targeted by *** underscores the intricate relationship between natural compounds such as nutlin-3 and immune *** comprehensive CRISPR screening,we validated the effects of specific ESLRS genes on low-grade glioma *** also revealed insights into the effectiveness of Nutlin-3a as a potent MDM2 inhibitor through molecular docking and dynamic ***-3a inhibited glioma cell proliferation and activated the p53 *** efficacy decreased with MDM2 overexpression,and this was reversed by Nutlin-3a or *** using a low-grade glioma mouse model highlighted the effect of physical activity on oxidative stress and molecular pathway ***,both physical exercise and Nutlin-3a administration improved physical function in mice bearing tumors derived from MDM2-overexpressing *** results suggest the potential for Nutlin-3a,an MDM2 inhibitor,with physical exercise as a therapeutic approach for glioma *** research also supports the use of natural products for therapy and sheds light on the interaction of exercise,natural products,and immune regulation in cancer treatment.

关键词： exercise and SUMO-related gene signatures(ESLRS) glioblastoma management low-grade glioma natural bioactives neural regeneration physical exercise

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Low temperature-mediated repression and far-red light-mediated induction determine morning FLOWERING LOCUS T expression levels

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Journal of Integrative Plant Biology 2024年第1期66卷 103-120页

作者： Hayeon Kim Hye Won kang Dae Yeon Hwang Nayoung Lee Akane Kubota Takato Imaizumi Young hun Song Department of Agricultural Biotechnology Seoul National UniversitySeoul 08826Korea Department of Biology Ajou UniversitySuwon 16499Korea Plant Genomics and Breeding Institute Seoul National UniversitySeoul 08826Korea Graduate School of Science and Technology Nara Institute of Science and TechnologyIkomaNara 630‐0192Japan Department of Biology University of WashingtonSeattleWA 98195USA Institute of Agricultural Life Sciences Seoul National UniversitySeoul 08826Korea

In order to flower in the appropriate season,plants monitor light and temperature changes and alter downstream pathways that regulate florigen genes such as Arabidopsis(Arabidopsis thaliana)FLOWERING LOCUS T(FT).In Arabidopsis,FT messenger RNA levels peak in the morning and evening under natural long-day conditions(LDs).However,the regulatory mechanisms governing morning FT induction remain poorly *** morning FT peak is absent in typical laboratory LDs characterized by high red:far-red light(R:FR)ratios and constant ***,we demonstrate that ZEITLUPE(ZTL)interacts with the FT repressors TARGET OF EATs(TOEs),thereby repressing morning FT expression in natural *** LDs with simulated sunlight(R:FR=1.0)and daily temperature cycles,which are natural LD-mimicking environmental conditions,FT transcript levels in the ztl mutant were high specifically in the morning,a pattern that was mirrored in the toe1 toe2 double *** night-to-morning temperatures increased the inhibitory effect of ZTL on morning FT expression by increasing ZTL protein levels early in the ***-red light counteracted ZTL activity by decreasing its abundance(possibly via phytochrome A(phyA))while increasing GIGANTEA(GI)levels and negatively affecting the formation of the ZTL-GI complex in the ***,the phyA-mediated high-irradiance response and GI play pivotal roles in morning FT *** findings suggest that the delicate balance between low temperature-mediated ZTL activity and the far-red light-mediated functions of phyA and GI offers plants flexibility in fine-tuning their flowering time by controlling FT expression in the morning.

关键词： far-red light FLOWERING LOCUS T flowering time GIGANTEA low night-to-morning temperature natural long days phytochrome A red to far-red ratio ZEITLUPE

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The Arabidopsis bZIP1 Transcription Factor Is Involved in Sugar Signaling, Protein Networking, and DNA Binding

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Molecular Plant 2010年第2期3卷 361-373页

作者： Shin Gene kang John Price Pei-Chi Lin jong Chan Hong Jyan-Chyun Jang Department of Horticulture and Crop Science The Ohio State University Columbus OH 43210 USA Plant Biotechnology Center The Ohio State University Columbus OH 43210 USA Department of Plant Cellular and Molecular Biology The Ohio State University Columbus OH 43210 USA Department of Biochemistry Gyeongsang National University Jinju Gyeongnam 660-701 Korea

Sugar signaling is a mechanism that plants use to integrate various internal and external cues to achieve nutrient homeostasis, mediate developmental programs, and articulate stress responses. Many bZlP transcription factors are known to be involved in nutrient and/or stress signaling. An Arabidopsis Sl-group bZlP gene, AtbZIP1, was identified as a sugar-sensitive gene in a previous gene expression profiling study （Plant Cell. 16, 2128-2150）. In this report, we show that the expression of AtbZIP1 is repressed by sugars in a fast, sensitive, and reversible way. The sugar repression of Atb- ZIP1 is affected by a conserved sugar signaling component, hexokinase. Besides being a sugar-regulated gene, AtbZIP1 can mediate sugar signaling and affect gene expression, plant growth, and development. When carbon nutrients are limited, gain or loss of function of AtbZlP1 causes changes in the rates of early seedling establishment. Results of phenotypic analyses indicate that AtbZlP1 acts as a negative regulator of early seedling growth. Using gain- and loss-of-function plants in a microarray analysis, two sets of putative AtbZIP1-regulated genes have been identified. Among them, sugar-responsive genes are highly over-represented, implicating a role of AtbZlP1 in sugar-mediated gene expression. Using yeast two-hybrid （Y-2-H） screens and bimolecular fluorescence complementation （BiFC） analyses, we are able to recapitulate extensive C/S1 AtbZlP protein interacting network in living cells. Finally, we show that AtbZIP1 can bind ACGT-based motifs in vitro and that the binding characteristics appear to be affected by the heterodimerization between AtbZlP1 and the C-group AtbZIPs, including AtbZlP10 and AtbZlP63.

关键词： bZIP transcription factors sugar response protein dimerization microarray analysis BiFC EMSA ACGT motif.

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Prediction of genetic alterations from gastric cancer histopathology images using a fully automated deep learning approach

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World Journal of Gastroenterology 2021年第44期27卷 7687-7704页

作者： Hyun-jong Jang Ahwon Lee Jun kang In Hye Song Sung Hak Lee Catholic Big Data Integration Center Department of PhysiologyCollege of MedicineThe Catholic University of KoreaSeoul 06591South Korea Department of Hospital Pathology Seoul St.Mary’s HospitalCollege of MedicineThe Catholic University of KoreaSeoul 06591South Korea

BACKGROUND Studies correlating specific genetic mutations and treatment response are ongoing to establish an effective treatment strategy for gastric cancer(GC).To facilitate this research,a cost-and time-effective method to analyze the mutational status is *** learning(DL)has been successfully applied to analyze hematoxylin and eosin(H and E)-stained tissue slide *** To test the feasibility of DL-based classifiers for the frequently occurring mutations from the H and E-stained GC tissue whole slide images(WSIs).METHODS From the GC dataset of The Cancer Genome Atlas(TCGA-STAD),wildtype/mutation classifiers for CDH1,ERBB2,KRAS,PIK3CA,and TP53 genes were trained on 360×360-pixel patches of tissue *** The area under the curve(AUC)for the receiver operating characteristic(ROC)curves ranged from 0.727 to 0.862 for the TCGA frozen WSIs and 0.661 to 0.858 for the TCGA formalin-fixed paraffin-embedded(FFPE)*** performance of the classifier can be improved by adding new FFPE WSI training dataset from our *** classifiers trained for mutation prediction in colorectal cancer completely failed to predict the mutational status in GC,indicating that DL-based mutation classifiers are incompatible between different *** This study concluded that DL could predict genetic mutations in H and E-stained tissue slides when they are trained with appropriate tissue data.

关键词： Gastric cancer Mutation Deep learning Digital pathology Formalin-fixed paraffin-embedded

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Prediction of clinically actionable genetic alterations from colorectal cancer histopathology images using deep learning

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World Journal of Gastroenterology 2020年第40期26卷 6207-6223页

作者： Hyun-jong Jang Ahwon Lee J kang In Hye Song Sung Hak Lee Department of Physiology Department of Biomedicine and Health SciencesCatholic Neuroscience InstituteThe Catholic University of KoreaSeoul 06591South Korea Department of Hospital Pathology Seoul St.Mary’s HospitalCollege of MedicineThe Catholic University of KoreaSeoul 06591South Korea

BACKGROUND Identifying genetic mutations in cancer patients have been increasingly important because distinctive mutational patterns can be very informative to determine the optimal therapeutic strategy. Recent studies have shown that deep learning-based molecular cancer subtyping can be performed directly from the standard hematoxylin and eosin(H&E) sections in diverse tumors including colorectal cancers(CRCs). Since H&E-stained tissue slides are ubiquitously available, mutation prediction with the pathology images from cancers can be a time-and cost-effective complementary method for personalized *** To predict the frequently occurring actionable mutations from the H&E-stained CRC whole-slide images(WSIs) with deep learning-based *** A total of 629 CRC patients from The Cancer Genome Atlas(TCGA-COAD and TCGA-READ) and 142 CRC patients from Seoul St. Mary Hospital(SMH) were included. Based on the mutation frequency in TCGA and SMH datasets, we chose APC, KRAS, PIK3CA, SMAD4, and TP53 genes for the study. The classifiers were trained with 360 × 360 pixel patches of tissue images. The receiver operating characteristic(ROC) curves and area under the curves(AUCs) for all the classifiers were *** The AUCs for ROC curves ranged from 0.693 to 0.809 for the TCGA frozen WSIs and from 0.645 to 0.783 for the TCGA formalin-fixed paraffin-embedded *** prediction performance can be enhanced with the expansion of datasets. When the classifiers were trained with both TCGA and SMH data, the prediction performance was *** APC, KRAS, PIK3CA, SMAD4, and TP53 mutations can be predicted from H&E pathology images using deep learning-based classifiers, demonstrating the potential for deep learning-based mutation prediction in the CRC tissue slides.

关键词： Colorectal cancer Mutation Deep learning Computational pathology Computer-aided diagnosis Digital pathology

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Mapping the Dementia Research Area at the Micro-Level Using Co-terms Analysis and Positioning for Traditional Herbal Medicine

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Chinese Journal of Integrative Medicine 2014年第9期20卷 706-711页

作者： Bu-Yeo Kim jong Seok kang ung-Soo Han Won Kyung Jeon Herbal Medicine Research Division Korea Institute of Oriental MedicineDaejeon 305-811Republic of Korea Information Analysis Center Korea Institute of S&T InformationSeoul 130-741Republic of Korea Department of Biological Science Konkuk UniversitySeoul 143-701Republic of Korea

Objective： To identify the position of traditional herbal medicine in dementia research field using mapping technology. Methods： Keywords for dementia and traditional herbal medicine for treating dementia were used to extract scientific articles from the Web of Science database from January 2000 to July 2010. A co- occurrence matrix was created based on the concurrent set of author＇s keywords occurring in each scientific article, and technology network maps were created from similarity index matrices. Results： Twenty specialized research areas were identified in the dementia field, and the relationship strength was 0.2-0.6. Many research fields were associated with diagnosis and risk factors for dementia. Additionally, the mechanism or cause of dementia is an actively studied field. Traditional herbal medicine for treating dementia was located on a map near the cortical dementia diagnosis and therapy, and frontotemporal dementia research field with a relationship strength of 0.53 and 0.31-0.33 respectively, which demonstrates that traditional herbal medicine for dementia occupies an independent research area with a relationship to existing scientific research fields. Conclusion： Traditional herbal medicine can provide an alternative and complementary approach for treating dementia as evidenced by a scientific mapping analysis.

关键词： dementia mapping positioning traditional herbal medicine

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Loss of CDX2 expression is associated with poor prognosis in colorectal cancer patients

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World Journal of Gastroenterology 2015年第5期21卷 1457-1467页

作者： Jeong Mo Bae Tae hun Lee Nam-Yun Cho Tae-You Kim Gyeong Hoon kang Laboratory of Epigenetics Cancer Research InstituteSeoul National University College of MedicineSeoul 110-799South Korea Department of Pathology Seoul National University College of MedicineSeoul 110-799South Korea Department of Internal Medicine Seoul National University College of MedicineSeoul 110-799South Korea

AIM:To investigate the clinicopathologic characteristics and prognostic implications associated with loss of CDX2 expression in colorectal cancers(CRCs).METHODS:We immunohistochemically evaluated CDX2 expression in 713 CRCs and paired our findings to clinicopathologic and molecular characteristics of each *** included cytokeratin 7 and CK20 expression,microsatellite instability,Cp G island methylator phenotype,and KRAS and BRAF mutation *** and multivariate survival analysis was performed to reveal the prognostic value of CDX2 ***:CDX2 expression was lost in 42(5.9%) ***,loss of CDX2 expression was associated with proximal location,infiltrative growth,advanced T,N,M and overall *** microscopic examination,loss of CDX2 expression was associated with poor differentiation,increased number of tumor-infiltrating lymphocytes,luminal serration and mucin *** of CDX2 expression was also associated with increased CK7 expression,decreased CK20 expression,Cp G island methylator phenotype,microsatellite instability and BRAF *** a univariate survival analysis,patients with loss of CDX2 expression showed worse overall survival(P < 0.001) and progression-free survival(P < 0.001).In a multivariate survival analysis,loss of CDX2 expression was an independent poor prognostic factor of overall survival [hazard ratio(HR) = 1.72,95%CI:1.04-2.85,P = 0.034] and progression-free survival(HR = 1.94,95%CI:1.22-3.07,P = 0.005).CONCLUSION:Loss of CDX2 expression is associated with aggressive clinical behavior and can be used as a prognostic marker in CRCs.

关键词： CDX2 CpG island methylator phenotype Microsatellit

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Brain endothelial cell-derived extracellular vesicles with a mitochondria-targeting photosensitizer effectively treat glioblastoma by hijacking the blood-brain barrier

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Acta Pharmaceutica Sinica B 2023年第9期13卷 3834-3848页

作者： Thuy Giang Nguyen Cao Ji Hee kang Su Jin kang Quan Truong Hoang Han Chang kang Won jong Rhee Yu Shrike Zhang Young Tag Ko Min Suk Shim Division of Bioengineering Incheon National UniversityIncheon 22012Republic of Korea College of Pharmacy Gachon UniversityIncheon 21936Republic of Korea Department of Pharmacy Integrated Research Institute of Pharmaceutical Sciencesand BK21 PLUS Team for Creative Leader Program for Pharmacomics-based Future PharmacyCollege of Pharmacythe Catholic University of KoreaGyeonggi-do 14662Republic of Korea Research Center for Bio Materials&Process Development Incheon National UniversityIncheon 22012Republic of Korea Division of Engineering in Medicine Department of MedicineBrigham and Women’s HospitalHarvard Medical SchoolCambridgeMA 02139USA

Glioblastoma(GBM)is the most aggressive malignant brain tumor and has a high mortality *** therapy(PDT)has emerged as a promising approach for the treatment of malignant brain ***,the use of PDT for the treatment of GBM has been limited by its low blood-brain barrier(BBB)permeability and lack of cancer-targeting ***,brain endothelial cell-derived extracellular vesicles(bEVs)were used as a biocompatible nanoplatform to transport photosensitizers into brain tumors across the *** enhance PDT efficacy,the photosensitizer chlorin e6(Ce6)was linked to mitochondria-targeting triphenylphosphonium(TPP)and entrapped into *** Ce6(TPP-Ce6)selectively accumulated in the mitochondria,which rendered brain tumor cells more susceptible to reactive oxygen species-induced apoptosis under light ***,the encapsulation of TPP-Ce6 into b EVs markedly improved the aqueous stability and cellular internalization of TPP-Ce6,leading to significantly enhanced PDT efficacy in U87MG GBM *** in vivo biodistribution study using orthotopic GBM-xenografted mice showed that b EVs containing TPP-Ce6[b EV(TPP-Ce6)]substantially accumulated in brain tumors after BBB penetration via transferrin receptor-mediated *** such,b EV(TPP-Ce6)-mediated PDT considerably inhibited the growth of GBM without causing adverse systemic toxicity,suggesting that mitochondria are an effective target for photodynamic GBM therapy.

关键词： Extracellular vesicle Chlorin e6 Triphenylphosphonium Mitochondria-targeting photosensitizer Photodynamic therapy Blood-brain barrier Glioblastoma Transferrin receptor

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Effect of Korean Magnolia obovata Extract on Platelet-Derived Growth Factor-Induced Vascular Smooth Muscle Cells

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Chinese Journal of Integrative Medicine 2020年第9期26卷 677-682页

作者： Hyunjhung Jhun Suji Baek Jinwoo Kim kang-Pa Lee hun-Young Park Won-Hwan Park Kiwon Lim Jisu Kim Technical Assistance Center Korea Food Research InstituteJeonbuk(55365)Republic of Korea Department of Medical Science School of MedicineKonkuk UniversitySeoulRepublic of Korea Department of Bio-Science College of Natural ScienceDongguk UniversityGyeongbuk(38066)Republic of Korea Physical Activity&Performance Institute Konkuk UniversitySeoul(05029)Republic of Korea Department of Diagnostic College of Korean MedicineDongguk University GoyangGyeonggi-do(10326)Republic of Korea

Objective:To investigate the effects of Korean Magnolia obovata crude extract(KME)on plateletderived growth factor(PDGF)-BB-induced proliferation and migration of vascular smooth muscle cells(VSMCs).Methods:KME composition was analyzed by high-performance liquid chromatography(HPLC).VSMCs were isolated from the aorta of a Sprague-Dawley rat,incubated in serum free-Dulbecco's modified Eagle's medium in the presence or absence of KME(10,30,100,and 300(xg/mL),then further treated with PDGF-BB(10 ng/mL).VSMC proliferation was detected using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and VSMC migration was determined using the Boyden chamber and scratch wound healing *** blot analysis was used to detect phosphorylation of extracellular signal-regulated protein kinases 1 and 2(p-ERK1/2),protein kinase B(p-Akt),and stress-activated protein kinase/c-Jun NH2-terminal kinase(p-SAPK/JNK).The antimigration and proliferation effects of KME were tested using aortic sprout ***:The HPLC analysis identified honokiol(0.45 mg/g)and magnolol(0.34 mg/g)as the major components of ***(30,100,and 300μg/m L)significantly decreased the proliferation and migration of PDGF-BB-stimulated(10 ng/mL)VSMCs and the PDGF-BB-induced phosphorylation of EKR1/2,Akt,and SAPK/JNK(P<0.05).Furthermore,PDGF-BBinduced VSMCs treated with 300μg/m L of KME showed reduction in aortic sprout ***:KME could inhibit abnormal proliferation and migration of VSMCs by down-regulating the phosphorylation of EKR1/2 and ***,KME might be a functional food for preventing vascular disorders.

关键词： extracellular signal-regulated protein kinases 1 and 2 Akt platelet-derived growth factor-BB smooth muscle cell functional food

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