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KML001, an arsenic compound, as salvage chemotherapy in refractory biliary tract cancers: A prospective study

Hepatobiliary & Pancreatic Diseases International 2019年第1期18卷 62-66页

作者： Jung Hyun Jo Huapyong Kang hee seung lee Moon Jae Chung Jeong Youp Park seungmin Bang seung Woo Park Si Young Song Division of Gastroenterology Department of Internal Medicine Severance Hospital Yonsei University College of Medicine

Background: Sodium meta-arsenite(NaAsO_2, KML001) is a potential oral anticancer agent acting on telomerase and telomere length. This prospective study evaluated its safety, tolerability, and effectiveness as salvage chemotherapy in patients with advanced biliary tract cancer(BTC) resistant to gemcitabinebased chemotherapy. Methods: Forty-four patients(21 women and 23 men) with advanced BTC and failure history of gemcitabine-based chemotherapy, performance status(PS) 0–2, normal cardiac, hepatic, and renal function were enrolled. Daily dose of KML001(7.5 mg. p.o.) was administered to eligible subjects for 24 weeks divided into six treatment cycles. Response was evaluated bimonthly using CT. Results: After an average of 1.5 months of treatment(range: 0.5–10.0), 3 patients(6.8%) obtained progression-free status, 23 patients(52.3%) had disease progression, and 18 patients(40.9%) dropped out before evaluation. One patient(2.3%) completed six treatment cycles without progression. During the treatment, morphine dosage kept the same or decreased in 20 patients(47.6%). Nine patients(20.5%) experienced grade-3 adverse events(AEs), while no patient experienced grade-4 AEs. The most common AEs were liver enzyme elevation(11/44, 25%) and anemia(10/44, 22.7%). KML001 was discontinued in six patients(13.6%) due to AEs, including liver toxicity( n = 3), QTc prolongation( n = 2), and abdominal pain( n = 1). Conclusions: KML001 did not have enough anticancer effect on patients with advanced BTC resistant to gemcitabine. However, KML001 was safe and well-tolerable in terms of AEs and pain control when used as salvage therapy. Further studies are needed to establish arsenic agents as a reliable treatment option in patients with BTC.

关键词： Biliary tract neoplasms Cholangiocarcinoma Gallbladder neoplasms KML001 Sodium meta-arsenite

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Revision of bilateral self-expandable metallic stents placed using the stent-in-stent technique for malignant hilar biliary obstruction

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Hepatobiliary & Pancreatic Diseases International 2018年第5期17卷 437-442页

作者： Jun Hyuk Son hee seung lee Sang Hyub lee seungmin Bang Jinwoo Kang Woo Hyun Paik Ji Kon Ryu Yong-Tae Kim Department of Internal Medicine and Liver Research Institute Seoul National University HospitalSeoul National University College of MedicineSeoulKorea Department of Internal Medicine Inje University Ilsan Paik HospitalGoyangKorea Department of Internal Medicine Institute of GastroenterologyYonsei University College of MedicineSeoulKorea Department of Gastroenterology and Hepatology SMG-SNU Boramae Medical CenterSeoulKorea

Background: Endoscopic biliary decompression using bilateral self-expandable metallic stent(SEMS) placed using the stent-in-stent(SIS) technique is considered favorable for unresectable malignant hilar biliary obstruction(MHBO). However, occlusion of the bilateral SIS placement is frequent and revision can be challenging. This study was performed to investigate the efficacy, the long-term patency and the appropriate approach for revision of occluded bilateral SIS placement in unresectable MHBO. Methods: From January 2011 to July 2016, thirty-eight patients with unresectable MHBO underwent revision of occluded bilateral SIS placement. Clinical data including success rates and patency of revision, were retrospectively analyzed. Results: The technical success rate of revision was 76.3%. The clinical success rate of revision was 51.7% and mean patency of revision was 49.1 days. No significant predictive factor for clinical failure of revision was observed. The cell size of SEMS was not found to have significant effects on clinical success rates or revision patency. Conclusions: Revision of occluded bilateral SIS placement for MHBO showed fair patency and clinical success rate. Revision method and cell size of SEMS were not found to influence clinical outcomes.

关键词： Malignant hilar biliary obstruction Self-expandable metallic stent Stent-in-stent Revision

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Comparison of efficacy and safety between standard-dose and modified-dose FOLFIRINOX as a first-line treatment of pancreatic cancer

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World Journal of Gastrointestinal Oncology 2018年第11期10卷 421-430页

作者： Huapyong Kang Jung Hyun Jo hee seung lee Moon Jae Chung seungmin Bang seung Woo Park Si Young Song Jeong Youp Park Division of Gastroenterology Department of Internal Medicine Yonsei University College of Medicine

AIM To directly compare the efficacy and toxicity of standarddose FOLFIRINOX(sFOLFIRINOX) and modified-dose FOLFIRINOX(mFOLFIRINOX, 75% of standard-dose) for pancreatic *** One hundred and thirty pancreatic cancer patients who received sFOLFIRINOX(n = 88) or mFOLFIRINOX(n = 42) as their first-line chemotherapy from January 2013 to July 2017 were retrospectively reviewed. For efficacy analysis, the objective response rate(ORR),disease control rate(DCR), progression-free survival(PFS), and overall survival(OS) were evaluated and compared using Pearson's chi-square test, Kaplan-Meier plot and log-rank test. The adverse events(AEs) were evaluated, and severe(≥ grade 3) AEs rates of the two groups were compared for toxicity *** The mFOLFIRINOX group included more female patients(30.7% vs 57.1%; P = 0.004) and older patients [age(median), 57 vs 63.5; P = 0.018] than the sFOLFIRINOX group. In the efficacy analysis, the ORR and DCR were not significantly different between the two groups(ORR: 39.8% vs 35.7%; P = 0.656; DCR: 80.7% vs 83.3%; P = 0.716). The median PFS and OS were also not different between the groups(PFS: 8.7 mo vs 8.1 mo, P = 0.272; OS: 13.9 mo vs 13.7 mo, P = 0.476). In the safety analysis with severe AEs, the rates of neutropenia(83.0% vs 66.7%; P = 0.044), anorexia(48.9% vs 28.6%; P = 0.029) and diarrhea(13.6% vs 0.0%; P = 0.009) were markedly lower in the mFOLFIRINOX *** m FOLFIRINOX showed comparable efficacy but better safety compared to sFOLFIRINOX. If clinically necessary, initiating FOLFIRINOX with 75% of the standard-dose can alleviate toxicity concerns without compromising efficacy.

关键词： Dose modification Adverse event Pancreatic cancer Adenocarcinoma FOLFIRINOX Chemotherapy

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Benefit of neoadjuvant concurrent chemoradiotherapy for locally advanced perihilar cholangiocarcinoma

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World Journal of Gastroenterology 2017年第18期23卷 3301-3308页

作者： Jang Han Jung Hyun Jik lee hee seung lee Jung Hyun Jo In Rae Cho Moon Jae Chung Jeong Youp Park seung Woo Park Si Young Song seungmin Bang Division of Gastroenterology Department of Internal Medicine Hallym University Dongtan Sacred Heart Hospital Division of Gastroenterology Department of Internal Medicine and Yonsei Institute of Gastroenterology Yonsei University College of Medicine

To clarify the role of neoadjuvant concurrent chemoradiotherapy (NACCRT) followed by surgical resection for localized or locally advanced perihilar cholangiocarcinoma (CCA).METHODSWe retrospectively reviewed 57 patients who underwent surgical resection with or without NACCRT for perihilar CCA; 12 patients received NACCRT and 45 patients did not received NACCRT. Patients with locally advanced perihilar CCA requiring NACCRT were defined as follows: (1) a mass involving unilateral branches of the portal vein or hepatic artery with insufficient volume of the anticipated remnant lobe; or (2) an infiltrating mass in the main portal vein that was too long for reconstruction, identified at preoperative *** median disease-free survival (DFS) durations of the neoadjuvant and non-neoadjuvant CCRT groups were 26.0 and 15.1 mo, respectively (P = 0.91). The median overall survival (OS) durations of the neoadjuvant and non-neoadjuvant CCRT groups were 32.9 and 27.1 mo, respectively (P = 0.26). The NACCRT group showed a downstaging tendency compared to the non-NACCRT group as compared with the tumor stage confirmed by histological examination after surgery and the tumor stage confirmed by imaging test at the time of diagnosis (P = 0.01).CONCLUSIONNACCRT does not prolong DFS and OS in localized or locally advanced perihilar CCA. However, NACCRT may allow tumor downstaging and improve tumor resectability.

关键词： Klatskin tumor Locally advanced Survival rate Neoadjuvant therapy Chemoradiotherapy

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Efficacy and safety of a patient-positioning device(EZ-FIX)for endoscopic retrograde cholangiopancreatography

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World Journal of Gastroenterology 2015年第19期21卷 5995-6000页

作者： seungho lee Joung-Ho Han hee seung lee Ki Bae Kim In-kwang lee Eun-Jong Cha Young Duck Shin Namgyu Park Seon Mee Park Department of Internal Medicine College of Medicine Chungbuk National University Department of Biomedical Engineering Chungbuk National University College of Medicine Department of Anesthesiology Chungbuk National University College of Medicine

AIM: To assess the efficacy and safety of a patientpositioning device(EZ-FIX) for endoscopic retrograde cholangiopancreatography(ERCP).METHODS: A total of 105 patients were randomized to the EZ-FIX(n = 53) or non-EZ-FIX(n = 52) group in this prospective study. Midazolam and propofol,titrated to provide an adequate level of sedation during therapeutic ERCP, were administered by trained registered nurses under endoscopist *** outcome measures were the total dose of propofol and sedative-related complications, including hypoxia and hypotension. Secondary outcome measures were recovery time and sedation satisfaction of the endoscopist, nurses, and ***: There was no significant difference in the rate of hypoxia, but there was a statistical trend(EX-FIX group; n = 4, 7.55%, control group; n = 6, 11.53%,P = 0.06). The mean total dose of propofol was lower in the EZ-FIX group than in the non-EZ-FIX group(89.43 ± 49.8 mg vs 112.4 ± 53.8 mg, P = 0.025).In addition, the EZ-FIX group had a shorter mean recovery time(11.23 ± 4.61 mg vs 14.96 ± 5.12 mg, P< 0.001). Sedation satisfaction of the endoscopist and nurses was higher in the *** group than in the nonEZ-FIX group. Technical success rates of the procedure were 96.23% and 96.15%, respectively(P = 0.856).Procedure-related complications did not differ by group(11.32% vs 13.46%, respectively, P = 0.735).CONCLUSION: Using EZ-FIX reduced the total dose of propofol and the recovery time, and increased the satisfaction of the endoscopist and nurses.

关键词： EZ-FIX Patient-positioning device Propofol Sedation Endoscopic retrograde cholangiopancreaRandomizedtography

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Tetradentate Pt(Ⅱ)complex as a singlet exciton sensitizing host for highly efficient green fluorescent organic light-emitting diodes

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Science China Materials 2024年第8期67卷 2618-2627页

作者： Unhyeok Jo seung Chan Kim Chan hee Ryu Kang Mun lee Jae-Min Kim Jun Yeob lee School of Chemical Engineering Sungkyunkwan University2066Seobu-roJangan-guSuwon-siGyeonggi-do 16419Republic of Korea Department of Chemistry Institute for Molecular Science and Fusion TechnologyKangwon National UniversityChuncheonGangwon 24341Republic of Korea Department of Advanced Materials Engineering Chung-Ang University4726Seodong-daeroDaedeok-myeonAnseong-siGyeonggi-do 17546Republic of Korea SKKU Advanced Institute of Nano Technology Sungkyunkwan University2066Seobu-roJangan-guSuwonGyeonggi 16419Republic of Korea SKKU Institute of Energy Science and Technology Sungkyunkwan University2066Seobu-roJangan-guSuwonGyeonggi 16419Republic of Korea

Efficient green fluorescent organic light-emitting diodes were designed with a phosphorescent metal complex as a singlet exciton sensitizing host(SESH)for achieving high efficiency and low efficiency roll-off through exciton and polaron *** Pt(Ⅱ)complex(Pt-Trz)possessing a tetradentate ligand with a bulky blocking group not only suppresses the severe formation of excimer or dimer itself but also transfers radiative excitons to fluorescent dopant *** SESH assisted fluorescence(SESHF)device with Pt-Trz as the host exhibits the maximum external quantum efficiency of 13.3%and a lower efficiency roll-off compared with exciplex host device which is a general approach for harvesting triplet *** exciton dynamics modeling unravels that the SESHF device effectively utilizes triplet excitons in the host by intersystem crossing and resonance energy transfer from the triplet state of the host to the singlet state of the terminal *** quenching rates of the SESHF device are reduced by 11 times for triplet-triplet annihilation and 1.8 times for tripletpolaron annihilation compared with the exciplex device,which demonstrates that Pt-Trz could be a platform to be used as an efficient host for fluorophores.

关键词： singlet annihilation polaron

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FOLFIRINOX vs gemcitabine/nab-paclitaxel for treatment of metastatic pancreatic cancer: Single-center cohort study

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World Journal of Gastrointestinal Oncology 2020年第2期12卷 182-194页

作者： In Rae Cho Huapyong Kang Jung Hyun Jo hee seung lee Moon Jae Chung Jeong Youp Park seung Woo Park Si Young Song Chansik An Mi-Suk Park seungmin Bang Department of Internal Medicine International Saint Mary’s HospitalCatholic Kwandong University College of MedicineIncheon 22711South Korea Department of Medicine Yonsei University Graduate School50-1 Yonsei-roSeoul 03722South Korea Division of Gastroenterology Department of Internal MedicineYonsei University College of Medicine50-1 Yonsei-roSeoul 03722South Korea Department of Radiology Yonsei University College of Medicine50-1 Yonsei-roSeoul 03722South Korea

BACKGROUND FOLFIRINOX and gemcitabine plus nab-paclitaxel(Gem+nabPTX)were recently introduced for metastatic pancreatic cancer ***,studies that compared these two regimens and studies in Asian populations are *** To compare the treatment outcomes of FOLFIRINOX and Gem+nabPTX regimen for metastatic pancreatic cancer treatment in Korean *** Patients with metastatic or recurrent pancreatic cancer treated with FOLFIRINOX(n=86)or Gem+nabPTX(n=81)as the first-line since January 2015 were identified using the Severance Hospital Pancreatic Cancer Cohort *** efficacy,treatment-related adverse events and economic aspects were *** Patients in the FOLFIRINOX group were significantly younger(54 vs 65 years;P<0.001)and had better performance statuses at *** median overall survival(10.7 vs 12.1 mo;P=0.157),progression-free survival(8.0 vs 8.4 mo;P=0.134),and objective response rates(33.7%vs 46.9%;P=0.067)were not significantly different when compared with Gem+nabPTX ***≥3 neutropenia and gastrointestinal adverse events were more common in the FOLFIRINOX *** drug costs of both regimens were *** Treatment efficacy and economic burdens were comparable between the two ***,the details of adverse event were ***+nabPTX regimen might be considered preferentially in certain conditions.

关键词： Pancreatic cancer Chemotherapy FOLFIRINOX Gemcitabine Nabpaclitaxel Survival

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Oncology Research 2024年第2期32卷 421-432页

作者： seung-hee GWAK JUHYUN lee EUNJI OH DOHYUN lee WONSHIK HAN JONGMIN KIM KYONG-TAI KIM Department of Life Sciences Pohang University of Science and TechnologyPohang37673Korea R&D Center NovMetaPharma Co.Ltd.Pohang37668Korea Department of Surgery and Cancer Research Institute Seoul National University College of MedicineSeoul03080Korea Generative Genomics Research Center Global Green Research&Development CenterHandong Global UniversityPohang37554Korea

Genetic information is transcribed from genomic DNA to mRNA,which is then translated into threedimensional *** can undergo various post-transcriptional modifications,including RNA editing that alters mRNA sequences,ultimately affecting protein *** this study,RNA editing was identified at the 499th base(c.499)of human vaccinia-related kinase 2(VRK2).This RNA editing changes the amino acid in the catalytic domain of VRK2 from isoleucine(with adenine base)to valine(with guanine base).Isoleucine-containing VRK2 has higher kinase activity than the valine-containing VRK2,which leads to an increase in tumor cell *** we reported that VRK2 directly interacts with dystrobrevin-binding protein(dysbindin)and results in reducing its ***,we demonstrate that isoleucine-containing VRK2 decreases the level of dysbindin than valinecontaining *** interacts with cyclin D and thereby regulates its expression and *** reduction in the level of dysbindin by isoleucine-containing VRK2 further enhances the cyclin D expression,resulting in increased tumor growth and reduction in survival *** has also been observed that in patient samples,VRK2 level was elevated in breast cancer tissue compared to normal breast ***,the isoleucine form of VRK2 exhibited a greater increase in breast cancer ***,it is concluded that VRK2,especially dependent on the 167th variant amino acid,can be one of the indexes of tumor progression and proliferation.

关键词： VRK2 Kinase activity Breast cancer Tumor RNA editing Cell proliferation Cell growth

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A dose-dependent bimodal switch by homologous Aux/IAA transcriptional repressors

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Molecular Plant 2024年第9期17卷 1407-1422页

作者： Hyung-Taeg Cho Minsu lee hee-seung Choi Kwang-Ho Maeng Kyeonghoon lee Ha-Yeon lee Anindya Ganguly Hoonyoung Park Chang-Hoi Ho Department of Biological Sciences Seoul National UniversitySeoulKorea School of Earth and Environmental Sciences Seoul National UniversitySeoulKorea Department of Climate and Energy Systems Engineering Ewha Womans UniversitySeoulKorea

Combinatorial interactions between different regulators diversify and enrich the chance of transcriptional regulation in eukaryotic ***,a dose-dependent functional switch of homologous transcriptional repressors has rarely been ***,we show that SHY2,an auxin/indole-3-acetic acid(Aux/IAA)repressor,exhibits a dose-dependent bimodal role in auxin-sensitive root-hair growth and gene transcrip-tion in Arabidopsis,whereas other Aux/lAA homologs consistently repress the auxin *** co-repressor(TOPLESS[TPL])-binding affinity of a bimodal Aux/IAA was lower than that of a consistently re-pressing Aux/*** switch of a single amino acid residue in the TPL-binding motif between the bimodal form and the consistently repressing form switched their TPL-binding affinity and transcriptional and bio-logical roles in auxin *** on these data,we propose a model whereby competition between homologous repressors with different co-repressor-binding affinities could generate a bimodal output at thetranscriptional anddevelopmental levels.

关键词： auxin Aux/IAA dose-dependent regulation root hair transcription TOPLESS(TPL)

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Efficacy of chemotherapy containing bevacizumab in patients with metastatic colorectal cancer according to programmed cell death ligand 1

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World Journal of Gastrointestinal Oncology 2024年第8期16卷 3521-3528页

作者： Shin Woo Kang Sung hee Lim Min-Ji Kim Jeeyun lee Young Suk Park Ho Yeong Lim Won Ki Kang seung Tae Kim Division of Hematology Oncology Department of MedicineSamsung Medical CenterSungkyunkwan University School of MedicineSeoul 06351South Korea Samsung Biomedical Research Institute Samsung Medical CenterSeoul 06351South Korea

BACKGROUND Bevacizumab,an anti-vascular endothelial growth factor(VEGF)monoclonal antibody,inhibits angiogenesis and reduces tumor *** VEGF-C,lactate dehydrogenase,and inflammatory markers have been reported as predictive markers related to bevacizumab *** cell death ligand 1(PD-L1)could act upon VEGF receptor 2 to induce cancer cell angiogenesis and *** To investigate the efficacy of bevacizumab-containing chemotherapy in patients with metastatic colorectal cancer(CRC)according to the expression of *** This analysis included CRC patients who received bevacizumab plus FOLFOX or FOLFIRI as first-line therapy between June 24,2014 and February 28,2022,at Samsung Medical Center(Seoul,South Korea).Analysis of patient data included evaluation of PD-L1 expression by the combined positive score(CPS).We analyzed the efficacy of bevacizumab according to PD-L1 expression status in patients with *** A total of 124 patients was included in this *** all patients were treated with bevacizumab plus FOLFIRI or FOLFOX as the first-line *** 77%of patients received FOLFOX,23%received FOLFIRI as backbone first-line *** numbers of patients with a PD-L1 CPS of 1 or more,5 or more,or 10 or more were 105(85%),64(52%),and 32(26%),*** results showed no significant difference in progression-free survival(PFS)and overall survival(OS)with bevacizumab treatment between patients with PDL1 CPS less than 1 and those with PD-L1 CPS of 1 or more(PD-L1<1%vs PD-L1≥1%;PFS:P=0.93,OS:P=0.33),between patients with PD-L1 CPS less than 5 and of 5 or more(PD-L1<5%vs PD-L1≥5%;PFS:P=0.409,OS:P=0.746),and between patients with PD-L1 CPS less than 10 and of 10 or more(PD-L1<10%vs PD-L1≥10%;PFS:P=0.529,OS:P=0.568).CONCLUSION Chemotherapy containing bevacizumab can be considered as first-line therapy in metastatic CRC irrespective of PD-L1 expression.

关键词： Bevacizumab Colorectal cancer Programmed cell death ligand 1 expression First-line chemotherapy Metastatic colorectal cancer

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