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Targeted therapy in gastric cancer:Personalizing cancer treatment based on patient genome

World Journal of Gastroenterology 2014年第8期20卷 2042-2050页

作者： Sun Min lim jae yun lim jae Yong Cho Division of Medical Oncology Department of Internal MedicineSeverance HospitalYonsei University College of MedicineSeoul 135-720South Korea Department of Medical Oncology Gangnam Severance HospitalYonsei University College of MedicineSeoul 135-720South Korea

Gastric cancer is the second leading cause of cancerrelated deaths *** cytotoxic chemotherapy has limited efficacy for metastatic gastric cancer,with an overall survival of approximately ten *** advances in high-throughput technologies have enabled the implementation of personalized cancer therapy for high-risk *** use of such high-throughput technologies,including microarray and next generation sequencing,have promoted the discovery of novel targets that offer new treatment strategies for patients lacking other therapeutic *** molecular pathways are currently under investigation as therapeutic targets in gastric cancer,including those related to the epidermal growth factor receptor family,the mesenchymal-epithelial transition factor axis,and the phosphatidylinositol 3-kinase-AKTmammalian target of rapamycin *** in molecular diagnostic tools further support the discovery of new molecular *** exist,however;not all patients can be tested for biomarkers,and numerous challenges hamper implementation of targeted therapy in clinical ***,the scale of tumor genomic profiling is rapidly outpacing our ability to appropriately synthesize all the information in order to optimally refine patient ***,clinicians must continue to educate themselves regarding new tools and frameworks,and to utilize multidisciplinary team science,comprised of oncologists,geneticists,pathologists,biologists and bioinformaticians,to successfully implement this genomic approach therapeutically.

关键词： Gastric cancer Targeted therapy Biomarker Microarray Sequencing

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Survival analysis based on human epidermal growth factor 2 status in stage Ⅱ-Ⅲ gastric cancer

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World Journal of Gastroenterology 2017年第41期23卷 7407-7414页

作者： Jang Ho Cho jae yun lim jae Yong Cho Division of Medical Oncology Department of Internal Medicine Gangnam Severance Hospital Yonsei University College of Medicine

AIM To investigate human epidermal growth factor 2(HER2) overexpression and validate its prognostic effect in stage Ⅱ-Ⅲ gastric *** We reviewed the data of patients who were diagnosed with gastric cancer between March 2008 and October 2013 at the Yonsei University Medical Center. Among these patients, 384 patients who met the inclusion criteria were analyzed retrospectively. RESULTS Thirty-two(8.3%) of the 384 stage Ⅱ-Ⅲ gastric cancer patients exhibited HER2 overexpression. The median follow-up duration was 26.0 mo. HER2-negative patients had superior recurrence-free survival(RFS) compared to HER2-positive patients(HR = 0.52, 95%CI: 0.30-0.89; P = 0.015). The median overall survival(OS) was significantly prolonged in the HER2-negative group compared with the HER2-positive group(55.0 mo vs 38.0 mo, HR = 0.43, 95%CI: 0.21-0.88, P = 0.021). OS was also prolonged in HER2-negative patients who received adjuvant chemotherapy compared to HER2-positive patients(55.0 vs 38.0mo, HR = 0.42, 95%CI: 0.18-1.00, P = 0.051). In patients who did not receive adjuvant chemotherapy,the median RFS was prolonged in the HER2-negative group compared to the HER2-positive group(not reached vs 12.0 mo, HR = 0.17, 95%CI: 0.06-0.49, P= 0.001). In a multivariate analysis, HER2 status(HR= 0.421, 95%CI: 0.206-0.861, P = 0.018) and Eastern Cooperative Oncology Group performance status(HR = 2.002, 95%CI: 1.530-2.618, P < 0.001) were independent predictors of *** Our findings showed that HER2-positive patients had inferior OS and RFS. Stage Ⅱ-Ⅲ HER2-positive patients might be potential candidates for targeted therapies involving trastuzumab.

关键词： Trastuzumab Gastric neoplasm Human epidermal growth factor 2

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Thioredoxin and thioredoxin-interacting protein as prognostic markers for gastric cancer recurrence

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World Journal of Gastroenterology 2012年第39期18卷 5581-5588页

作者： jae yun lim Sun Och Yoo Soon Won Hong Jong Won Kim Seung Ho Choi jae Yong Cho Department of Medical Oncology Gangnam Severance Cancer HospitalYonsei University College of MedicineSeoul 135-720South Korea Department of Pathology Gangnam Severance Cancer HospitalYonsei University College of MedicineSeoul 135-720South Korea Department of Surgery Gangnam Severance Cancer HospitalYonsei University College of MedicineSeoul 135-720South Korea

AIM:To evaluate the potential of thioredoxin (TXN) and thioredoxin-interacting protein (TXNIP) expression as biomarkers for predicting gastric cancer recurrence. METHODS:TXN and TXNIP expression levels were acquired from gene expression microarray data for 65 human gastric cancer tissues. We determined whether each gene expression level was associated with cancer recurrence and investigated the relationship between the two genes. For validation, the expression levels of TXN and TXNIP were measured by quantitative real- time reverse transcription polymerase chain reaction in 68 independent stage Ⅲ gastric cancer patients. The correlation between gene expression and cancer prognosis was evaluated. Immunohistochemical staining was performed to investigate the protein expression levels of TXN and TXNIP and to characterize the expression patterns of each protein. RESULTS:TXN was a prognosis-related gene (P = 0.009), whereas TXNIP, a TXN inhibitor, demonstrated a negative correlation with TXN in the gene expression microarray data. In the 68 stage Ⅲ patients, the expression levels of both TXN and TXNIP had a statistically significant effect on recurrence-free survival (RFS, P = 0.008 and P = 0.036, respectively). The low TXN and high TXNIP expression group exhibited a better prognosis than the other groups, and the high TXN and low TXNIP expression group exhibited a poorer prognosis (P < 0.001 for RFS and P = 0.001 for overall survival). More than half of the patients in the simulta-neously high TXN and low TXNIP expression group ex- perienced a recurrence within 1 year after curative surgery, and the 5-year survival rate of the patients in this group was 29%, compared with 89% in the low TXN and high TXNIP expression group. The TXN protein was overexpressed in 65% of the gastric cancer tissues, whereas the TXNIP protein was underexpressed in 85% of the cancer cells. In a correlation analysis, TXN and TXNIP were highly correlated with many oncogenes and tumor suppressors

关键词： Gastric cancer Thioredoxin Thioredoxin-interacting protein Biomarker Prognosis

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Overexpression of the M2 isoform of pyruvate kinase is an adverse prognostic factor for signet ring cell gastric cancer

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World Journal of Gastroenterology 2012年第30期18卷 4037-4043页

作者： jae yun lim Sun Och Yoon So Young Seol Soon Won Hong Jong Won Kim Seung Ho Choi jae Yong Cho Department of Medical Oncology Gangnam Severance Cancer HospitalYonsei University College of MedicineSeoul 135-720South Korea Department of Pathology Gangnam Severance Cancer HospitalYonsei University College of MedicineSeoul 135-720South Korea Department of Surgery Gangnam Severance Cancer HospitalYonsei University College of MedicineSeoul 135-720South Korea

AIM:To investigate M2 isoform of pyruvate kinase(PKM2) expression in gastric cancers and evaluate its potential as a prognostic biomarker and an anticancer ***:All tissue samples were derived from gastric cancer patients underwent curative gastrectomy as a primary *** and pathological information were obtained from the medical *** expression microarray data from 60 cancer and 19 noncancer gastric tissues were analyzed to evaluate the expression level of PKM2 *** microarrays were constructed from 368 gastric cancer *** was used to measure PKM2 expression and PKM2 positivity of cancer was determined by proportion of PKM2-positive tumor cells and staining *** between PKM2 expression and the clinicopathological factors was evaluated and the correlation between PKM2 and cancer prognosis was ***:PKM2 mRNA levels were increased more than 2-fold in primary gastric cancers compared to adjacent normal tissues from the same patients(log transformed expression level:7.6 ± 0.65 vs 6.3 ± 0.51,P < 0.001).Moreover,differentiated type cancers had significantly higher PKM2 mRNA compared to undifferentiated type cancers(log transformed expression level:7.8 ± 0.70 vs 6.7 ± 0.71,P < 0.001).PKM2 protein was mainly localized in the cytoplasm of primary cancer cells and detected in 144 of 368(39.1%) human gastric cancer ***2 expression was not related with stage(P = 0.811),but strongly correlated with gastric cancer differentiation(P < 0.001).Differentiated type cancers expressed more PKM2 protein than did the undifferentiated *** differentiated adenocarcinoma showed 63.6% PKM2-positive cells;in contrast,signet-ring cell cancers showed only 17.7% PKM2-positive ***,PKM2 expression was correlated with shorter overall survival(P < 0.05) independent of stage only in signet-ring cell ***:PKM2 expression might be an adverse prognostic factor for signet-rin

关键词： Gastric cancer M2 isoform of pyruvate kinase Biomarker Signet ring cell carcinoma Prognosis

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Novel N-doped multichannel carbon nanofiber architecture with porous CoS nanoprisms for high-performance potassium-ion batteries

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Rare Metals 2024年第3期43卷 971-983页

作者： jae Bong lim Seung-Keun Park Department of Advanced Materials Engineering Chung-Ang UniversityGyeonggi-do17546Republic of Korea Department of Intelligence Energy and Industry Chung-Ang UniversitySeoul06974Republic of Korea Western Seoul Center Korea Basic Science InstituteSeoul03759Republic of Korea

Potassium-ion batteries(PIBs)have gained significant attention as an alternative to lithium-ion batteries(LIBs)due to the abundance of potassium(K)and low ***,the difficulty in finding appropriate electrode materials that can efficiently store the larger K ions has hindered their practical ***,we report a novel anode material,N-doped multichannel carbon nanofibers embedded with porous CoS nanoprisms(CSP@NMCNF),for high-performance *** CSP@NMCNF was synthesized using a two-step strategy comprising of the electrospinning of Co acetate hydroxide nanoprism/binary polymer blend and a subsequent heat *** porous CoS nanoprisms with an anisotropic morphology were well aligned along the length axis of the N-doped multichannel carbon nanofibers,thus ensuring their structural stability during the repeated charge-discharge *** addition,numerous pores facilitated the transport of electrons and ***,the CSP@NMCNF anode exhibited excellent electrochemical performance,delivering a high specific capacity of 368 mAh·g^(-1)at 0.5 A·g^(-1)after 200 cycles and excellent rate capability(232 mAh·g^(-1)at 2.0 A·g^(-1)).

关键词： K-ion batteries Cobalt sulfide Multichannel structured composite Electrospinning Nanoprism Porous structure

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Synergistically coupling of Ni–Fe LDH arrays with hollow Co–Mo sulfide nanotriangles for highly efficient overall water splitting

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Rare Metals 2024年第2期43卷 522-532页

作者： yun jae Lee Seung-Keun Park Department of Advanced Materials Engineering Chung-Ang UniversityAnseongGyeonggi-do17546Republic of Korea Department of Intelligent Energy and Industry Chung-Ang University84 Heukseok-ro Dongjak-guSeoul06974Republic of Korea Western Seoul Center Korea Basic Science Institute150 Bugahyeon-roSeodaemun-guSeoul03759Republic of Korea

Developing bifunctional catalysts that can catalyze both oxygen evolution reaction(OER)and hydrogen evolution reaction(HER)is pivotal to commercializing large-scale water ***,a novel hollow nanotriangle composed of NiFe LDH-CoMoS_(x) heterojunction(H-CMSx@NiFe LDH)is proposed as a highly efficient bifunctional electrocatalyst for both OER and *** fabricate a heterojunction system,ultra-thin nickel–iron layered double hydroxide(NiFe LDH)nanosheets are uniformly electrodeposited onto a metal–organic framework-derived hollow CoMoS_(x) *** strong coupling of CoMoS_(x) and NiFe LDH catalysts forms the intimate heterojunction interfaces to facilitate interfacial charge transfer,which is favorable to enhance the bifunctional catalytic ***,the large void of CoMoS_(x) nanotriangles and interconnected ultra-thin NiFe LDH nanosheets result in good electrolyte penetration and gas ***,the as-prepared H-CMSx@NiFe LDH on nickel foam(NF)exhibits an impressive catalytic activity and durability for OER and HER activities,delivering a current density of 100 mA·cm^(−2) at the small overpotentials of 214 and 299 mV in OER and HER,***,H-CMSx@NiFe LDH/NF proves to be an effective electrode for an alkaline electrolyzer,as a voltage of only 1.99 V is enough to achieve a current density voltage of only 1.99 V is enough to achieve a current density of 400 mA·cm^(−2) with no degradation in performance over 50 h.

关键词： Overall water splitting Metal-organic framework Molybdenum sulfide Layered double hydroxide Heterojunction

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Laser‑Induced and MOF‑Derived Metal Oxide/Carbon Composite for Synergistically Improved Ethanol Sensing at Room temperature

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Nano-Micro Letters 2024年第6期16卷 210-220页

作者： Hyeongtae lim Hyeokjin Kwon Hongki Kang jae Eun Jang Hyuk‑Jun Kwon Department of Electrical Engineering and Computer Science DGISTDaegu 42988South Korea Convergence Research Advanced Centre for Olfaction DGISTDaegu 42988South Korea

Advancements in sensor technology have significantly enhanced atmospheric ***,metal oxide and carbon(MO_(x)/C)hybrids have gained attention for their exceptional sensitivity and room-temperature sensing ***,previous methods of synthesizing MO_(x)/C composites suffer from problems,including inhomogeneity,aggregation,and challenges in ***,we introduce a refined method that employs a metal–organic framework(MOF)as a precursor combined with direct laser *** inherent structure of MOFs ensures a uniform distribution of metal ions and organic linkers,yielding homogeneous MO_(x)/C *** laser processing facilitates precise micropatterning(<2μm,comparable to typical photolithography)of the MO_(x)/C *** optimized MOF-derived MO_(x)/C sensor rapidly detected ethanol gas even at room temperature(105 and 18 s for response and recovery,respectively),with a broad range of sensing performance from 170 to 3,400 ppm and a high response value of up to 3,500%.Additionally,this sensor exhibited enhanced stability and thermal resilience compared to previous MOF-based *** research opens up promising avenues for practical applications in MOF-derived sensing devices.

关键词： Metal-organic frameworks Metal oxide Carbon composite Laser Gas sensor

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Overexpression of miR-196b and HOXA10 characterize a poor-prognosis gastric cancer subtype

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World Journal of Gastroenterology 2013年第41期19卷 7078-7088页

作者： jae yun lim Sun Och Yoon So-Young Seol Soon Won Hong Jong Won Kim Seung Ho Choi Ju-Seog Lee jae Yong Cho Department of Medical Oncology Gangnam Severance Cancer HospitalYonsei University College of MedicineSeoul 135-720South Korea Department of Systems Biology Division of Cancer MedicineUniversity of Texas MD Anderson Cancer CenterHoustonTX 77030United States Department of Pathology Gangnam Severance Cancer HospitalYonsei University College of Medicine 135-720SeoulSouth Korea Department of Surgery Gangnam Severance Cancer HospitalYonsei University College of MedicineSeoul 135-720South Korea

AIM:To identify molecular biologic differences between two gastric adenocarcinoma subgroups presenting different prognoses through the analysis of microRNA and protein ***:Array technologies were used to generate1146 microRNAs and 124 proteins expression profiles of samples from 60 patients with gastric *** the integrative analysis,we used established mRNA expression data published in our previous *** mRNA expression levels were acquired from microarray data for 60 identical gastric cancer *** gastric adenocarcinoma subgroups with distinct mRNA expression profiles presented distinctly different *** and protein expression patterns were compared between gastric cancer tissue and normal gastric tissue and between two different prognostic *** expressed microRNA,associated mRNA,and protein in patients with poor-prognosis gastric cancer were validated by quantitative reverse transcription polymerase chain reaction and immunochemistry in independent ***:We obtained the expression data of 1146microRNAs and 124 cancer-related *** microRNAs were aberrantly expressed in the two prognostic groups and in cancer vs non-cancer tissues(P<0.05).In the poor-prognosis group,miR-196b,miR-135b,and miR-93 were up-regulated and miR-29c*was ***-196b expression positively correlated with Homeobox A10(HOXA10)expression(r=0.726,P<0.001),which was significantly increased in poor-prognosis patients(P<0.001).Comparing gastric cancer with non-cancer tissues,46/124 proteins showed differential expression(P<0.05);COX2(P<0.001)and cyclin B1(P=0.017)were clearly overexpressed in the poor-prognosis ***:Co-activation of miR-196b and HOXA10characterized a poor-prognosis subgroup of patients with gastric *** of the biologic function of miR-196b and HOXA10 is warranted.

关键词： Gastric cancer Gene expression Microarray MicroRNA miR-196b Homeobox A10

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Validity of fatty liver prediction scores for diagnosis of fatty liver by Fibroscan

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Hepatobiliary & Pancreatic Diseases International 2024年第4期23卷 353-360页

作者： Seogsong Jeong Sun jae Park Seong Kyun Na Sang Min Park Byung-Cheol Song yun Hwan Oh Department of Biomedical Sciences Seoul National University Graduate SchoolSeoul 03080Korea Department of Biomedical Informatics CHA University School of MedicineCHA UniversitySeongnam 13488Korea Department of Internal Medicine Inje University College of MedicineSeoul 50834Korea Department of Family Medicine Seoul National University HospitalSeoul National University College of MedicineSeoul 03080Korea Department of Internal Medicine Jeju National University HospitalJeju National University College of MedicineJeju 63241Korea Department of Family Medicine Jeju National University HospitalJeju National University College of MedicineJeju 63241Korea Department of Family Medicine Chung-Ang University Gwangmyeong HospitalChung-Ang University College of MedicineGwangmyeong 14353Korea

Background:The Korea National Health and Nutrition Examination Survey nonalcoholic fatty liver disease(K-NAFLD)score was recently developed with the intent to operationally define nonalcoholic fatty liver disease(NAFLD).However,there remained an external validation that confirmed its diagnostic performance,especially in patients with alcohol consumption or hepatitis virus ***:Diagnostic accuracy of the K-NAFLD score was evaluated in a hospital-based cohort consisting of 1388 participants who received Fibroscan®.Multivariate-adjusted logistic regression models and the contrast estimation of receiver operating characteristic curves were used for validation of the K-NAFLD score,fatty liver index(FLI),and hepatic steatosis index(HSI).Results:K-NAFLD-moderate[adjusted odds ratio(aOR)=2.53,95%confidence interval(CI):1.13-5.65]and K-NAFLD-high(aOR=4.14,95%CI:1.69-10.13)groups showed higher risks of fatty liver compared to the K-NAFLD-low group after adjustments for demographic and clinical characteristics,and FLI-moderate and FLI-high groups revealed aORs of 2.05(95%CI:1.22-3.43)and 1.51(95%CI:0.78-2.90),*** addition,the HSI was less predictive for Fibroscan®-defined fatty *** K-NAFLD and FLI also demonstrated high accuracy in the prediction of fatty liver in patients with alcohol consumption and chronic hepatitis virus infection,and the adjusted area under curve values were comparable between K-NAFLD and ***:Externally validation of the K-NAFLD and FLI showed that these scores may be a useful,noninvasive,and non-imaging modality for the identification of fatty *** addition,these scores also predicted fatty liver in patients with alcohol consumption and chronic hepatitis virus infection.

关键词： Nonalcoholic fatty liver disease Fatty liver index Hepatic steatosis index

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Random pinhole attenuator for high-power laser beams

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High Power Laser Science and Engineering 2024年第3期12卷 116-121页

作者： Seong Cheol Park Hyeok yun Jin Woo Yoon Seong Ku Lee jae Hee Sung Il Woo Choi Chang Hee Nam Kyung Taec Kim Department of Physics and Photon Science Gwangju Institute of Science and TechnologyGwangjuRepublic of Korea Center for Relativistic Laser Science Institute for Basic ScienceGwangjuRepublic of Korea Advanced Photonics Research Institute Gwangju Institute of Science and TechnologyGwangjuRepublic of Korea

The intensity attenuation of a high-power laser is a frequent task in the measurements of optical *** intensity can be attenuated by inserting an optical element,such as a partial reflector,polarizer or absorption *** devices are,however,not always easily applicable,especially in the case of ultra-high-power lasers,because they can alter the characteristics of a laser beam or become easily *** this study,we demonstrated that the intensity of a laser beam could be effectively attenuated using a random pinhole attenuator(RPA),a device with randomly distributed pinholes,without changing the beam *** this device,a multi-PW laser beam was successfully attenuated and the focused beam profile was measured without any alterations of its *** addition,it was confirmed that the temporal profile of a laser pulse,including the spectral phase,was ***,the RPA possesses significant potential for a wide range of applications.

关键词： high-power laser intensity attenuation laser diagnostics

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