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All-in-one glycol chitosan nanoparticles for co-delivery of doxorubicin and anti-PD-L1 peptide in cancer immunotherapy

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Bioactive Materials 2023年第10期28卷 358-375页

作者： Sukyung Song Man Kyu Shim Suah Yang Jaewan Lee Wan Su Yun Hanhee Cho Yujeong Moon Jin young Min Eun hee Han Hong Yeol Yoon Kwangmeyung Kim College of Pharmacy Graduate School of Pharmaceutical SciencesEwha Womans UniversitySeoul03760Republic of Korea Medicinal Materials Research Center Biomedical Research DivisionKorea Institute of Science and Technology(KIST)Seoul02792Republic of Korea KU-KIST Graduate School of Converging Science and Technology Korea UniversitySeoul02841Republic of Korea Department of Bioengineering Korea UniversitySeoul02841Republic of Korea Research Center for Bioconvergence Analysis Korea Basic Science Institute(KBSI)Cheongju28119Republic of Korea Department of Toxicology College of PharmacyChungnam National UniversityDaejeon34134Republic of Korea

Synergistic immunotherapy of immune checkpoint blockade (ICB) and immunogenic cell death (ICD) has shown remarkable therapeutic efficacy in various cancers. However, patients show low response rates and undesirable outcomes to these combination therapies owing to the recycling mechanism of programmed death-ligand 1 (PD-L1) and the systemic toxicity of ICD-inducing chemotherapeutic drugs. Herein, we propose all-in-one glycol chitosan nanoparticles (CNPs) that can deliver anti-PD-L1 peptide (PP) and doxorubicin (DOX) to targeted tumor tissues for a safe and more effective synergistic immunotherapy. The PP-CNPs, which are prepared by conjugating ᴅ-form PP (NYSKPTDRQYHF) to CNPs, form stable nanoparticles that promote multivalent binding with PD-L1 proteins on the targeted tumor cell surface, resulting in effective lysosomal PD-L1 degradation in contrast with anti-PD-L1 antibody, which induces recycling of endocytosed PD-L1. Consequently, PP-CNPs prevent subcellular PD-L1 recycling and eventually destruct immune escape mechanism in CT26 colon tumor-bearing mice. Moreover, the ICD inducer, DOX is loaded into PP-CNPs (DOX-PP-CNPs) for synergistic ICD and ICB therapy, inducing a large number of damage-associated molecular patterns (DAMPs) in targeted tumor tissues with minimal toxicity in normal tissues. When the DOX-PP-CNPs are intravenously injected into CT26 colon tumor-bearing mice, PP and DOX are efficiently delivered to the tumor tissues via nanoparticle-derived passive and active targeting, which eventually induce both lysosomal PD-L1 degradation and substantial ICD, resulting in a high rate of complete tumor regression (CR: 60%) by a strong antitumor immune response. Collectively, this study demonstrates the superior efficacy of synergistic immunotherapy using all-in-one nanoparticles to deliver PP and DOX to targeted tumor tissues.

关键词： Chitosan nanoparticle Synergistic immunotherapy Immune checkpoint blockade Multivalent binding Immunogenic cell death

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Safety and efficacy of tenofovir in chronic hepatitis B-related decompensated cirrhosis

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World Journal of Gastroenterology 2017年第13期23卷 2396-2403页

作者： Soon Kyu Lee Myeong Jun Song Seok Hyun Kim Byung Seok Lee Tae hee Lee young Woo kang Suk Bae Kim Il Han Song hee Bok Chae Soon young Ko Jae Dong Lee Division of Hepatology Department of Internal MedicineDaejeon St.Mary's HospitalCollege of MedicineThe Catholic University of Korea Department of Internal Medicine Chungnam University Hospital Department of Internal Medicine Konyang University Hospital Department of Internal Medicine Dankook University Hospital Department of Internal Medicine Chung Buk University Hospital Department of Internal Medicine Konkuk University Chungju Hospital

AIM To evaluate the safety and efficacy of tenofovir disoproxil fumarate(TDF) as a first-line therapy in decompensated liver disease. METHODS We enrolled 174 chronic hepatitis B-related liver cirrhosis patients treated with 300 mg/d TDF at six Korean centers. Of the 174 cirrhosis patients, 57 were assigned to the decompensated cirrhosis group and 117 were assigned to the compensated cirrhosis group. We followed the patients for 12 mo and evaluated clinical outcomes, including biochemical, virological, and serological responses. We also evaluated changes in hepatic and renal function and compared the decompensated and compensated cirrhosis groups. RESULTS The 1-year complete virological response(CVR) and Hepatitis B e antigen(HBe Ag) seroconversion were seen in 70.2% and 14.2% in the decompensated cirrhosis group, respectively. The rates of HBe Ag seroconversion/loss and ALT normalization at month 12 were similar in both groups. TDF treatment was also effective for decreasing the level of hepatitis B virus(HBV) DNA in both groups, but CVR was higher in the compensated group(88.9% vs 70.2%, P = 0.005). Tenofovir treatment for 12 mo resulted in improved Child-Turcotte-Pugh(CTP) and model for end-stage liver disease(MELD) scores in decompensated group(P < 0.001). Of the 57 decompensated patients, 39(68.4%) achieved CTP class A and 27(49.1%) showed improvement in the CTP score of 2 points after 12 mo of TDF. The observed rate of confirmed 0.5 mg/d L increases in serum levels of creatinine in the decompensated and compensated cirrhosis group were 7.0% and 2.5%, respectively(P < 1.000).CONCLUSION TDF therapy in decompensated cirrhosis patients was effective for decreasing HBV DNA levels and improving hepatic function with relatively lower CVR than in compensated cirrhosis. Thus, physicians should carefully monitor not only renal function but also treatment responses when using TDF in decompensated cirrhosis patients.

关键词： Tenofovir 患心脏代偿失调的肝肝硬化补偿的肝肝硬化 Virological 反应肾的安全

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Clinical implications of neutrophil-to-lymphocyte ratio and MDSC kinetics in gastric cancer patients treated with ramucirumab plus paclitaxel

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Chinese Journal of Cancer Research 2020年第5期32卷 621-630页

作者： Hyung-Don Kim Min-hee Ryu Sangsoon Yoon young-Soon Na Meesun Moon Hyungeun Lee Hyung Geun Song Yoon-Koo kang Department of Oncology Asan Medical CenterUniversity of Ulsan College of MedicineSeoul 05505Republic of Korea Asan Institute for Life Science Asan Medical CenterUniversity of Ulsan College of MedicineSeoul 05505Republic of Korea DiNonA Inc Seoul 05505Korea

Objective: We aimed to investigate the prognostic value of neutrophil-to-lymphocyte ratio(NLR) and myeloidderived suppressor cells(MDSCs) in gastric cancer patients treated with second-line ramucirumab plus ***: A total of 116 patients with advanced or metastatic gastric cancer who receive ramucirumab plus paclitaxel were prospectively enrolled. Fresh blood samples were collected before and after treatment, and flow cytometry was performed to assess the proportions of monocytic(m MDSCs) and granulocytic MDSCs(g MDSCs).Results: Median age was 58 years and 71(61.2%) patients were male. A baseline NLR≥2.94 was associated with significantly poorer progression-free survival(PFS) and overall survival(OS) vs. an NLR<2.94(P=0.011 and P=0.002, respectively). In multivariate analysis, an NLR≥2.94 was independently associated with poorer PFS[hazard ratio(HR)=1.58;95% confidence interval(95% CI): 1.01-2.49, P=0.046] and OS(HR=1.77;95% CI:1.04-3.04, P=0.036). While m MDSC counts did not significantly change following two cycles of therapy(P=0.530),g MDSC counts decreased significantly after two treatment cycles(P=0.025) but tended to increase in patients with progressive disease after two treatment cycles(P=0.098). A progressive increase in g MDSC counts(≥44%) was associated with a significantly shorter PFS and OS vs. a g MDSC count increase <44%(P=0.001 and P=0.003,respectively).Conclusions: The baseline NLR may help guide clinical decisions during ramucirumab plus paclitaxel therapy for gastric cancer. Our g MDSC kinetics data warrant further clinical validation and mechanistic investigation.

关键词： Gastric cancer ramucirumab plus paclitaxel neutrophil-to-lymphocyte ratio myeloid-derived suppressor cells

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Analysis of interval constants in calendars affiliated with the Shoushili

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Research in Astronomy and Astrophysics 2014年第4期14卷 485-496页

作者： Byeong-hee Mihn Ki-Won Lee young Sook Ahn Advanced Astronomy and Space Science Division Korea Astronomy and Space Science Institute Department of Astronomy and Space Science Chungbuk National University Institute of Liberal Education Catholic University of Daegu

We study interval constants that are related to motions of the Sun and Moon, i.e., the Qi, Intercalation, Revolution and Crossing interval, in calendars affiliated with the Shoushi calendar （Shoushili）, such as Datongli and Chiljeongsannaepyeon. It is known that these interval constants were newly introduced in the Shoushili calendar and revised afterward, except for the Qi interval constant, and the revised values were adopted in later calendars affiliated with the Shoushili. We first investigate the accu- racy of these interval constants and then the accuracy of calendars affiliated with the Shoushili in terms of these constants by comparing times for the new moon and the maximum solar eclipse calculated by each calendar with modem methods of calcula- tion. During our study, we found that the Qi and Intercalation interval constants used in the early Shoushili were well determined, whereas the Revolution and Crossing interval constants were relatively poorly measured. We also found that the interval constants used by the early Shoushili were better than those of the later one, and hence better than those of Datongli and Chiljeongsannaepyeon. On the other hand, we found that the early Shoushili is, in general, a worse calendar than Datongli for use in China but a better one than Chiljeongsannaepyeon for use in Korea in terms of times for the new moon and when a solar eclipse occurs, at least for the period 1281 - 1644. Finally, we verified that the times for sunrise and sunset in the Shoushili-Li-Cheng and Mingshi are those at Beijing and Nanjing, respectively.

关键词： history and philosophy of astronomy: general -- celestial mechanics --ephemerides

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Risk stratification for disease progression in pT3 prostate cancer after robot-assisted radical prostatectomy

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Asian Journal of Andrology 2017年第6期19卷 700-706页

作者： Jeong hee Hong young Suk Kwon Isaac Yi Kim Section of Urologic Oncology Rutgers Cancer Institute of New Jersey Division of Urology Rutgers Robert Wood Johnson Medical School Rutgers The State University of New Jersey New Brunswick NJ 08903 USA Department of Urology Dankook University College of Medicine Cheonan 31116 South Korea.

The aim of this study is to identify optimal patients for adjuvant radiation therapy （ART） in pT3 prostate cancer. The role of ART for patients with adverse pathologic features after radical prostatectomy （RP） has been demonstrated, but over- or under-treatment remains a significant concern. Two-hundred and five patients with pT3NOMO who underwent robot-assisted RP without ART were analyzed. Multivariate Cox proportional regression analyses were used to identify predictors of biochemical recurrence （BCR） and clinical progression （CP）. The estimated 5-year BCR-free survival （BCRFS） and CP-free survival （CPFS） were 52.8% and 85.6%, respectively. Preoperative prostate-specifc antigen （PSA）：〉10 ng m1-1 （hazard ratio [HR]： 3.288-6.027; P = 0.003）, pathologic Gleason score （pGS）：〉8 （HR： 4.146; P = 0.014）, and lymphovascular invasion （LVI）（HR： 2.167; P = 0.026） were associated with BCR. Based on these factors, a risk stratification tool was developed. Patients with no risk factors （PSA 〈10 ng m1-1, pGS 6, and absent LVI） showed excellent BCRFS and CPFS at 5 years （91.9% and 100.0%, respectively）, but those with two or more risk factors （PSA ：〉10 ng ml-1, pGS ≥8, or present LVI） had poor BCRFS and CPFS （12.1% and 54.6%, respectively）. In addition, the multivariate analysis revealed that pathologic stage pT3b （HR： 5.393; P = 0.025） was the only predictor of CP. Our study demonstrated the heterogeneity of oncologic outcomes in patients with pT3 prostate cancer. The proposed risk stratification can be used to identify patients who are at risk for disease progression and may aid in identifying the best patients for ART.

关键词： prostatectomy prostate-specific antigen recurrence survival

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A density functional theory study of the tunable structure, magnetism and metal-insulator phase transition in VS2 monolayers induced by in-plane biaxial strain

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Nano Research 2015年第4期8卷 1348-1356页

作者： Min Kan Bo Wang young hee Lee Qiang Sun Department of Materials Science and Engineering Peking University 8eijing 100871 China Center for Integrated Nanostructure Physics Institute for Basic Science Sungkyunkwan University Suwon 440-746 Korea Department of Physics and Department of Energy Science Sungkyunkwan University Suwon 440-746 Korea School of Mathematical Sciences Peking University Beijing 100871 China Center forAppfied Physics and Technology Peking University Beijing 100871 China

我们报导密度阶段转变的功能的理论学习一 VS 能被在里面飞机 biaxial 紧张调节的 2 单层。这导致金属绝缘体转变和低纺纱高度旋转磁性的转变。在低温度，半导体的 H 阶段是稳定、大的紧张 >3% 被要求挑起转变。在房间温度 300 K，在... 详细信息

我们报导密度阶段转变的功能的理论学习一 VS 能被在里面飞机 biaxial 紧张调节的 2 单层。这导致金属绝缘体转变和低纺纱高度旋转磁性的转变。在低温度，半导体的 H 阶段是稳定、大的紧张 >3% 被要求挑起转变。在房间温度 300 K，在另一方面，仅仅 2% 的小张力的紧张被需要从高纺纱和磁性的转变从半导体的 H 阶段导致阶段转变到金属性的 T 阶段到低纺纱。紧张和温度上的阶段图依赖也被讨论以便提供阶段稳定性的更好的理解对 2 单层。

关键词：密度泛函理论拉伸应变绝缘体金属单层双轴面内相变

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Pancreatic pseudocyst filled with semisolid lipids mimicking solid mass on endoscopic ultrasound

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World Journal of Gastroenterology 2010年第8期16卷 1034-1038页

作者： Sang-Woo Cha Sae hee Kim Hyang Ie Lee Yun Jung Lee Hyeon Woong Yang Sung hee Jung Anna Kim Min Koo Lee Hyun young Han Dong Wook kang Division of Gastroenterology Department of Internal Medicine Eulji University College of Medicine Eulji University Hospital Division of Gastroenterology Department of Surgery Eulji University College of Medicine Eulji University Hospital Division of Gastroenterology Department of Radiology Eulji University College of Medicine Eulji University Hospital Division of Gastroenterology Department of Pathology Eulji University College of Medicine Eulji University Hospital

Pancreatic pseudocysts,which account for 70%-90% of pancreatic cystic lesions,characteristically are non-epithelially lined cystic cavities that are contiguous with the pancreas. Pancreatic pseudocysts can be caused by acute,chronic or traumatic pancreatitis and should be differentiated from other pancreatic diseases with cystic appearances,especially cystic neoplasms. We report a unique case of a pancreatic pseudocyst filled with semisolid lipids,which appeared by endoscopic ultrasound as a solid mass,and was therefore resected.

关键词： Pancreatic pseudocyst Lipids Endosonog-raphy

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Clinical significance of MET gene amplification in metastatic or locally advanced gastric cancer treated with first-line fluoropyrimidine and platinum combination chemotherapy

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Chinese Journal of Cancer Research 2019年第4期31卷 620-631页

作者： Seyoung Seo Min-hee Ryu Baek-Yeol Ryoo Yangsoon Park young Soo Park young-Soon Na Chae-Won Lee Ju-Kyung Lee Yoon-Koo kang Departments of Oncology Asan Medical CenterUniversity of Ulsan College of MedicineSeoul 05505Republic of Korea Department of Pathology Asan Medical CenterUniversity of Ulsan College of MedicineSeoul 05505Republic of Korea Asan Institute for Life Science Asan Medical CenterUniversity of Ulsan College of MedicineSeoul 05505Republic of Korea

Objective: To investigate the clinical significance of MET gene amplification in patients with gastric cancer in the palliative ***: MET amplification was assessed using fluorescence in situ hybridization(FISH) in 50 patients and quantitative polymerase chain reaction(qPCR) in 326 patients;259 patients treated with first-line fluoropyrimidine and platinum were included for survival ***: The results of FISH and qPCR indicated that the c-MET/CEP7 ratio was correlated with gene copy number. The optimal cutoff value for the copy number using qPCR to detect MET gene amplification with FISH was 5(κ=0.778, P5 detected by qPCR. MET-amplified gastric cancer was associated with an Eastern Cooperative Oncology Group(ECOG) performance status(PS) score of ≥2(33.3% vs. 10.5% P=0.007), peritoneal metastasis(76.2% vs. 46.2%, P=0.008), and elevated bilirubin levels(28.6% vs. 7.3%, P=0.006). The median overall survival(OS) and progression-free survival(PFS) were 11.9 and 5.6 months, respectively. MET-amplified gastric cancer was not associated with survival outcomes [hazard ratio(HR)=0.68, 95% confidence interval(95% CI): 0.35-1.32,P=0.254 for PFS;HR=0.68, 95% CI: 0.35-1.32, P=0.251 for OS].Conclusions: qPCR can be used to detect MET gene amplification. MET amplification was not a predictor of poor prognosis in patients with metastatic or unresectable gastric cancer.

关键词： MET amplification advanced gastric cancer prognosis quantitative real-time polymerase chain reaction

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Acoustic radiation force impulse elastography for hepatocellular carcinoma-associated radiofrequency ablation

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World Journal of Gastroenterology 2011年第14期17卷 1874-1878页

作者： hee-Jin Kwon Myong-Jin kang Jin-Han Cho Jong-young Oh Kyung-Jin Nam Sang-Yeong Han Sung Wook Lee Department of Radiology Dong-A University HospitalDongdaesindong 3gaSeo-guPusan 602-715South Korea Department of Internal Medicine Dong-A University HospitalDongdaesindong 3gaSeo-guPusan 602-715South Korea

AIM:To evaluate the potential usefulness of acoustic radiation force impulse (ARFI) images for evaluation of hepatocellular carcinomas (HCC)-associated radiofrequency ablation. METHODS:From January 2010 to June 2010,a total of 38 patients with HCC including recurred HCCs after RFA underwent ARFI elastography. The brightness of tumor was checked and the shear wave velocity was measure-d for the-quantification of stiffne-ss. According to theb-rightne-ss,the-tumors we-re-classifie-d as b-righte-r,samecolor and darker compared with adjacent parenchyma. Using the same methods,8 patients with recurred HCCs after RFA state were evaluated about the brightness compared with adjacent RFA ablation area. RESULTS:In the 38 patients with HCCs,20 (52.6%)were brighter than surrounding cirrhotic parenchyma. Another 13 (34.2%) were darker. The others (5 cases,13.2%) were seen as the same color as the adjacent liver parenchyma. Post-RFA lesions were darker than previous tumor and surrounding parenchyma in all 38 cases. However,recurred HCCs were brighter than the treated site in all 8 cases. CONCLUSION:Using ARFI technique is helpful for differential diagnosis in order to detect recurred HCCs more easily in patients with confusing status.

关键词：射频消融辐射力肝癌成像弹性治疗 RFA 亮度比

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Association between the early high level of serum tacrolimus and recurrence of hepatocellular carcinoma in ABO-incompatible liver transplantation

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World Journal of Gastrointestinal Surgery 2023年第12期15卷 2727-2738页

作者： Ji Won Han Jong young Choi Eun Sun Jung Ji Hoon Kim hee Sun Cho Jae-Sung Yoo Pil Soo Sung Jeong Won Jang Seung Kew Yoon Ho Joong Choi young Kyoung You Department of Internal Medicine The Catholic University of KoreaSeoul 06591South Korea The Catholic University Liver Research Center College of MedicineThe Catholic University of KoreaSeoul 06591South Korea Department of Hospital Pathology The Catholic University of KoreaSeoul 06591South Korea Department of Surgery The Catholic University of KoreaSeoul 06591South Korea

BACKGROUND Clinical factors predicting graft survival(GS)after ABO-incompatible(ABOi)liver transplantation(LT),and differences between recipients with and without hepatocellular carcinoma(HCC)are *** To analyze the impact of serial serum tacrolimus trough concentration in recipients with or without(HCC)in ABOi living-donor liver transplantation(LDLT).METHODS We analyzed a historical cohort of 89 recipients who underwent ABOi LDLT,including 47 patients with *** The 1-,3-,5-,and 10-year GS rates were 85.9%,73.3%,71.4%,and 71.4%,respectively,and there were no significant differences between HCC and non-HCC *** multivariate Coxregression analyses,tacrolimus trough concentrations below 5.4 ng/mL at 24 wk post-LT,in addition to the antibody-mediated rejection(AMR)were associated with poor-graft *** HCC patients,AMR[hazard ratio(HR)=63.20,P7.3 ng/mL were significant predictive factors for HCC *** propensity score matching,patients with high tacrolimus concentrations at 4 wk had significantly poor recurrence-free *** Elevated tacrolimus levels at 4 wk after ABOi LDLT have been found to correlate with HCC ***,careful monitoring and control of tacrolimus levels are imperative in ABOi LT recipients with HCC.

关键词： ABO-incompatible Liver transplantation Tacrolimus Hepatocellular carcinoma

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