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Identification of novel HLA-A 0201-restricted epitopes from anterior gradient-2 as a tumor-associated antigen against colorectal cancer

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Cellular & Molecular Immunology 2012年第2期9卷 175-183页

作者： Hyun Ju Lee Cheol Yi Hong Chun-Ji jin Mi-Hyun kim Youn-Kyung Lee Thanh-Nhan Nguyen-Pham Hyunah Lee Byoung Chul Park ik-Joo Chung Hyeoung-Joon kim Je-Jung Lee Research Center for Cancer Immunotherapy Chonnam National University Hwasun Hospital Hwasun Jeollanamdo Korea Department of Hematology-Oncology Chonnam National University Gwangju Korea VaxcelI-Bio Therapeutics Hwasun Jeollanamdo Korea Samsung Medical Center Sungkyunkwan University School of Medicine Seoul Korea Korea Research Institute of Bioscience and Biotechnology （KRIBB） Daejeon Korea The Brain Korea 21 Project Center for Biomedical Human Resources at Chonnam National University Gwangiu Korea

Anterior gradient-2 （AGR2） promotes tumor growth, cell migration and cellular transformation and its enhanced expression is almost completely restricted to malignant tissues, thus making AGR2 an interesting target for the development of immunotherapeutic strategies. We investigated whether the AGR2 molecule comprises human leukocyte antigen （HLA）-A 0201-binding epitopes recognized by human cytotoxic T lymphocytes （CTLs）, which could be targeted in dendritic cell （DC）-based cancer immunotherapy against colorectal cancer （CRC）. We reviewed the sequence of AGR2 for peptides that could potentially bind to HLA-A 0201 with the aid of a computer-based program. Five candidate peptides with different binding scores were synthesized and tested. These peptides were then assessed for their immunogenicity to elicit specific immune responses mediated by CTLs in vitro by means of enzyme-linked immunospot assays and CTL assays. AGR2 was highly expressed in several CRC cell lines, including DK01, DLD1, KM 12C, HCT-8 and HT-29. DCs pulsed with AGR2-P2 （aa 11-19; LLVALSYTL） or AGR2-P4 （aa 127-135; RIMFVDPSL） generated potent CTLs that could lyse T2 cells pulsed with AGR2-P2 or AGR2-P4 and HLA-A0201＋ AGR2-positive CRC cell lines in a strong dose-dependent and HLA-A 0201-restricted manner. In conclusion, these novel epitopes derived from AGR2 protein may be attractive candidates for DC-based immunotherapy for CRC.

关键词： AGR2 colorectal cancer dendritic cell tumor-associated antigen

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Bacteroides fragilis enterotoxin upregulates heme oxygenase-1 in dendritic cells via reactive oxygen species-,mitogen-activated protein kinase-,and Nrf2-dependent pathway

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World Journal of Gastroenterology 2020年第3期26卷 291-306页

作者： Su Hyuk Ko Jong ik Jeon Hyun Ae Woo Jung Mogg kim Department of Microbiology and Department of Biomedical Science Hanyang University College of Medicine and Graduate School of Biomedical Science and EngineeringSeoul 04763South Korea Graduate School of Pharmaceutical Sciences Ewha Womans UniversitySeoul 03760South Korea

BACKGROUND Enterotoxigenic Bacteroides fragilis(ETBF)causes colitis and diarrhea,and is considered a candidate pathogen in inflammatory bowel diseases as well as colorectal *** diseases are dependent on ETBF-secreted toxin(BFT).Dendritic cells(DCs)play an important role in directing the nature of adaptive immune responses to bacterial infection and heme oxygenase-1(HO-1)is involved in the regulation of DC *** To investigate the role of BFT in HO-1 expression in *** Murine DCs were generated from specific pathogen-free C57BL/6 and Nrf2−/−knockout *** were exposed to BFT,after which HO-1 expression and the related signaling factor activation were measured by quantitative RT-PCR,EMSA,fluorescent microscopy,immunoblot,and *** HO-1 expression was upregulated in DCs stimulated with *** BFT activated transcription factors such as NF-κB,AP-1,and Nrf2,activation of NF-κB and AP-1 was not involved in the induction of HO-1 expression in BFT-exposed ***,upregulation of HO-1 expression was dependent on Nrf2 activation in ***,HO-1 expression via Nrf2 in DCs was regulated by mitogenactivated protein kinases such as ERK and ***,BFT enhanced the production of reactive oxygen species(ROS)and inhibition of ROS production resulted in a significant decrease of phospho-ERK,phospho-p38,Nrf2,and HO-1 CONCLUSION These results suggest that signaling pathways involving ROS-mediated ERK and p38 mitogen-activated protein kinases-Nrf2 activation in DCs are required for HO-1 induction during exposure to ETBF-produced BFT.

关键词： Bacteroides fragilis enterotoxin Dendritic cells Heme oxygenase-1 Mitogen-activated protein kinases Nrf2 Signaling

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Sarcopenia:Clinical implications in ovarian cancer,diagnosis,etiology,and management

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Sports Medicine and Health Science 2020年第4期2卷 202-210页

作者： Aeran Seol Se ik kim Yong Sang Song Department of Obstetrics and Gynecology Seoul National University College of MedicineSeoulRepublic of Korea Cancer Research Institute Seoul National University College of MedicineSeoulRepublic of Korea

Sarcopenia,loss of skeletal muscle and function,is a common condition among the elderly and is known to cause adverse health outcomes and increased risk of morbidity and *** progressive and generalized disorder imposes a considerable socioeconomic *** is observed commonly in cancer *** Asia is one of the fastest aging regions in the world,it is clear that incidences of both sarcopenia and ovarian cancer will increase together in Asian *** cancer patients are vulnerable to develop sarcopenia during the treatment course and progress of disease,and a considerable number of patients with ovarian cancer seems to have physical inactivity and sarcopenia already at the time of ***,management of sarcopenia should be conducted together in parallel with ovarian cancer treatment and ***,in this article,we will review the clinical importance of sarcopenia in the aspect of ovarian *** of sarcopenia,diagnosis,etiology,and intervention will be also introduced.

关键词： Sarcopenia Ovarian carcinoma Definition Physiology Practice Intervention

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Survival outcome of patients with spontaneously ruptured hepatocellular carcinoma treated surgically or by transarterial embolization

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World Journal of Gastroenterology 2013年第28期19卷 4537-4544页

作者： Young-Joo jin jin-Woo Lee Seoung-Wook Park Jung Il Lee Don Haeng Lee Young Soo kim Soon Gu Cho Yong Sun Jeon Kun Young Lee Seung-ik Ahn Department of Internal Medicine Inha University Hospital Inha University School of Medicine Incheon 400-711 South Korea Department of Internal Medicine Yonsei University College of Medicine Seoul 120-752 South Korea Department of Internal Medicine and Center for Advanced Medical Education by Brain Korea 21 Project Inha University School of Medicine and Utah-Inha DDS and Advanced Therapeutics Research Center Incheon 400-711 South Korea Department of Radiology Inha University Hospital Inha University School of Medicine Incheon 400-711 South Korea Department of Surgery Inha University Hospital Inha University School of Medicine Incheon 400-711 South Korea

AIM: To evaluate clinical outcomes of patients that underwent surgery, transarterial embolization (TAE), or supportive care for spontaneously ruptured hepatocellular carcinoma (HCC). METHODS: A consecutive 54 patients who diagnosed as spontaneously ruptured HCC at our institution between 2003 and 2012 were retrospectively enrolled. HCC was diagnosed based on the diagnostic guidelines issued by the 2005 American Association for the Study of Liver Diseases. HCC rupture was defined as disruption of the peritumoral liver capsule with enhanced fluid collection in the perihepatic area adjacent to the HCC by dynamic liver computed tomography, and when abdominal paracentesis showed an ascitic red blood cell count of > 50000 mm 3 /mL in bloody fluid. RESULTS: Of the 54 patients, 6 (11.1%) underwent surgery, 25 (46.3%) TAE, and 23 (42.6%) supportive care. The 2-, 4and 6-mo cumulative survival rates at 2, 4 and 6 mo were significantly higher in the surgery (60%, 60% and 60%) or TAE (36%, 20% and 20%) groups than in the supportive care group (8.7%, 0% and 0%), respectively (each, P < 0.01), and tended to be higher in the surgical group than in the TAE group. Multivariate analysis showed that serum bilirubin (HR = 1.09, P < 0.01), creatinine (HR = 1.46, P = 0.04), and vasopressor requirement (HR = 2.37, P = 0.02) were significantly associated with post-treatment mortality, whereas surgery (HR = 0.41, P < 0.01), and TAE (HR = 0.13, P = 0.01) were inversely associated with posttreatment mortality. CONCLUSION: Post-treatment survival after surgery or TAE was found to be better than after supportive care, and surgery tended to provide better survival benefit than TAE.

关键词： Ruptured hepatocellular carcinoma Surgery Transarterial embolization

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Cardiac metastasis from colorectal cancer:A case report

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World Journal of Gastroenterology 2009年第21期15卷 2675-2678页

作者： Pyong Wha Choi Chul Nam kim Sun Hee Chang Woo ik Chang Chang Young kim Hyun Min Choi Department of Surgery Ilsan Paik HospitalInje University College of Medicine Department of Diagnostic Pathology Ilsan Paik HospitalInje University College of Medicine Department of Chest Surgery Ilsan Paik HospitalInje University College of Medicine Department of Internal Medicine Ilsan Paik HospitalInje University College of Medicine

The heart is an unusual site of metastasis from any malignancy. We report a case of cardiac metastasis from colorectal cancer. A 70-year-old woman was referred with a presumptive diagnosis of sigmoid colon cancer with cardiac myxoma. Two-dimensional echocardiography showed a 4 cm x 4.5 cm mobile mass on the lateral right atrial wall, and computed tomography revealed a low attenuated Iobulating mass in the right atrium. The patient underwent anterior resection for sigmoid colon cancer （T4N2）. Thereafter, she experienced progressive shortness of breath. Therefore, a cardiac operation was performed 2 wk after the colorectal operation. Histological examination revealed adenocarcinoma, which was identical to the primary lesion. Although two- dimensional echocardiography has become the diagnostic test of choice for detecting cardiac tumors, in patients with colorectal cancer showing a cardiac mass, further diagnostic evaluation such as a magnetic resonance imaging might be necessary.

关键词： Heart Cardiac metastasis Colorectalcancer Atrial myxoma Magnetic resonance imaging

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Rapid Establishment of Tracheal Stenosis in Pigs Using Endotracheal Tube Cuff Overpressure and Electrocautery

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Current Medical Science 2021年第2期41卷 329-335页

作者： jin Hyoung kim Jong Joon Ahn Yangin Jegal Soohyun Bae Soon Eun Park Moon Sik Jung Ju ik Park Hee Jeong Cha Yongjik Lee Taehoon Lee Division of Respiratory and Critical Care Medicine Department of Intemnal MedicineUlsan University HospitalUniversity of Ulsan College of MedicineUlsan 44033Korea Department of Anesthesiology and Pain Medicine UIsan University HospitalUniversity of Ulsan College of MedicineUlsan 44033Korea Department of Pathology Ulsan University HospitalUniversity of Ulsan College of MedicineUlsan 44033Korea Department of Thoracic and Cardiovascular Surgery Ulsan University HospitalUniversity of Ulsan College of MedicineUlsan 44033Korea

To apply a new airway treatment to humans, preclinical studies in an appropriate animalmodel is needed. Canine, porcine and leporine tracheas have been employed as animal airwaystenosis models using various methods such as chemical caustic agents, laser, and ***, existing models take a long time to develop (3- 8 weeks) and the mechanism of stenosisis different from that in humans. The aim of the present study was to establish a new and fasttracheal stenosis model in pigs using a combination of cuff overpressure intubation (COI) andelectrocautery. Fourteen pigs were divided into three groups: tracheal cautery (TC) group (n=3),COI group (n=3), and COI-TC combination group (n=8). Cuff overpressure (200/400/500 mmHg)was applied using a 9-mm endotracheal tube. Tracheal cautery (40/60 watts) was performed usinga rigid bronchoscopic electrocoagulator. After intervention, the pigs were observed for 3 weeks andbronchoscopy was performed every 7 days. When the cross-sectional area decreased by > 50%, itwas confirmed that tracheal stenosis was established. The time for tracheal stenosis was 14 days inthe TC group and 7 days in the COI-TC combination group. In the COI group, no stenosis *** the COI-TC group, electrocautery (40 watts) immediately after intubation for>1 h with a cufpressure of 200 mmHg or more resulted in suficient tracheal stenosis within 7 days. Moreover, thedegree of tracheal stenosis increased in proportion to the cuff pressure and tracheal intubation *** combined use of cuf overpressure and electrocautery helped to establish tracheal stenosis inpigs rapidly.

关键词： pig tracheal stenosis model cuff overpressure electrocautery

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Clinical significance of tumor-infiltrating lymphocytes for gastric cancer in the era of immunology

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World Journal of Gastrointestinal Oncology 2017年第7期9卷 293-299页

作者： Byung Woog Kang Jong Gwang kim In Hee Lee Han ik Bae An Na Seo Department of Hematology/Oncology Kyungpook National University Hospital Kyungpook National University School of Medicine Department of Pathology Kyungpook National University Hospital Kyungpook National University School of Medicine

Immunotherapy has begun to revolutionize cancer treatment, by introducing therapies that target the host immune system instead of the tumor, therapies that possess unique adverse event profiles, and therapies that may cure certain types of cancer. The immune microenvironment of tumors is emerging as the most important means of understanding the relationship between a patient' immune system and their cancer, informing prognosis, and guiding immunotherapy, such as an antibody blockade of immune checkpoints. For some solid tumors, simple quantitation of lymphocyte infiltration would seem to have prognostic significance, suggesting that lymphocyte infiltration is not passive but may actively promote or inhibit tumor growth. For gastric cancers, several studies have provided strong evidence that immune cells contribute to determining prognosis. However, the exact role of immune cells in gastric cancer remains unclear. Therefore, this review focuses on the clinical significance of immune cells, especially tumor-infiltrating lymphocytes, in gastric cancer.

关键词： Gastric cancer Tumor-infiltrating lymphocytes Immunotherapy

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New Discovery of the Early Cretaceous Volcanic Rocks on the Barton Peninsula,King George Island,Antarctica and Its Geological Significance

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Acta Geologica Sinica(English Edition) 2000年第2期74卷 176-182页

作者： ZHENG Xiangshen SANG Haiqing QIU Ji LIU Jiaqi LEE Jong ik kim Hyeoncheol Institute of Geology and Geophysics Chinese Academy of SciencesBeijing 100029China Polar Research Center Korea Ocean Research and Development InstituteSeoul 425-600Korea

Ages determined with the 40Ar/39Ar isotopic system affirms the Early Cretaceous volcanic activity in the Barton Peninsula, King George Island, Antarctica. Two specimens of basaltic andesite collected from the lower-most volcanic sequence of the peninsula were irradiated and analyzed in different experiments, yielding an identical age spectrum, and two magmatic thermal events of the Early Cretaceous (120.4±1.6 Ma, 119±1 Ma) and Early Tertiary (53.1±1.5 Ma, 52±1 Ma) are distinguished. The former is interpreted to represent the primary cooling age of basaltic andesite, whereas the latter is the thermal reset age caused by the intrusion of granitic pluton. These new ages clearly indicate that volcanism was active during the Early Cretaceous on the Barton Peninsula and that intensive hydrothermal alteration and mineralization of Mesozoic volcanic rocks resulted from Tertiary magmatism.

关键词： Antarctica Barton Peninsula volcanic rocks ^(40)Ar/^(39)Ar age

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Die Casting Mold Design of the Thin-walled Aluminum Case by Computational Solidification Simulation

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Journal of Materials Science & Technology 2008年第3期24卷 383-388页

作者： Young-Chan kim Chang-Seog Kang Jae-ik Cho Chang-Yeol Jeong Se-Weon Choi Sung-Kil Hong Korea Institute of Industrial Technology Chonnam National University

Recently, demand for the lightweight alloy in electric/electronic housings has been greatly increased. However, among the lightweight alloys, aluminum alloy thin-walled die casting is problematic because it is quite difficult to achieve sufficient fluidity and feedability to fill the thin cavity as the wall thickness becomes less than 1mm. Therefore, in this study, thin-walled die casting of aluminum （Al-Si-Cu alloy： ALDC 12） in size of notebook computer housing and thickness of 0.8 mm was investigated by solidification simulation （MAGMA soft） and actual casting experiment （Buhler Evolution B 53D）. Three different types of gating design, finger, tangential and split type with 6 vertical runners, were simulated and the results showed that sound thin-walled die casting was possible with tangential and split type gating design because those gates allowed aluminum melt to flow into the thin cavity uniformly and split type gating system was preferable gating design comparing to tangential type gating system at the point of view of soundness of casting and distortion generated after solidification. Also, the solidification simulation agreed well with the actual die-casting and the casting showed no casting defects and distortion.

关键词： Aluminum casting alloy Thin-wall die casting Solidification simulation

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Intraoperative radiofrequency ablation with or without tumorectomy for hepatocellular carcinoma in locations difficult for a percutaneous approach

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Hepatobiliary & Pancreatic Diseases International 2009年第6期8卷 591-596页

作者： Hyung Ook kim Seung Kwon kim Byung Ho Son Chang Hak Yoo Hyun Pyo Hong Yong Kyun Cho Byung ik kim Departments of Surgery Kangbuk Samsung Hospital Sungkyunkwan University School of Medicine Radiology Kangbuk Samsung Hospital Sungkyunkwan University School of Medicine Division of Interventional Radiology Mallinckrodt Institute of RadiologyWashington University School of Medicine Internal Medicine Kangbuk Samsung Hospital Sungkyunkwan University School of Medicine

BACKGROUND:Although hepatic resection is widely accepted as a proper modality for treating hepatocellular carcinoma(HCC),a majority of patients are unable to undergo surgical resection due to various tumor and patient *** ablation(RFA)has mostly been used as a therapeutic alternative to resection for treating *** objective of this study was to evaluate the results of intraoperative RFA for HCCs in locations difficult for a percutaneous ***:Eight patients(male,seven;age,49-67 years) with 8 HCCs in difficult locations were treated by intraoperative *** of the patients had local tumor progression after initial transarterial chemoembolization or ultrasound(US)guided percutaneous *** locations of the tumors were hepatic dome in six patients,posterior subcapsule in one,and caudate lobe in *** tumor size was 2.0 to 6.4 cm(mean,3.9 cm).Intraoperative RFA was performed at the tumor itself and an anticipated resection line under US guidance with 3 cm monopolar single or clustered internally cooled *** resection was performed in six *** month later,treatment response was assessed by contrast material-enhanced computed tomography(CT).CT studies were performed every 2 or 3 months after ***:RFA was technically successful in all tumors,and the contrast-enhanced CT images acquired one month later showed complete disappearance of tumor *** pneumothorax *** a median follow-up of 18 months(range,6-30 months),no tumors showed local *** the follow-up period,four new recurrent tumors were observed in three *** patients were alive at the time of this report and the other four died of hepatorenal syndrome,liver failure,and progression of new recurrent ***:Intraoperative RFA with tumor resection can be an alterative treatment option for HCC in locations difficult for a percutaneous approach.

关键词： hepatocellular carcinoma radiofrequency ablation intraoperative

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