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Dramatic Response to Cabozantinib in a Patient with Refractory Hepatocellular Carcinoma with c-MET Amplification

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Journal of Clinical and Translational Hepatology 2023年第3期11卷 747-750页

作者： Yun beom Sang Gwangil kim Sohyun Hwang Haeyoun Kang Hong Jae Chon Department of Medical Oncology CHA Bundang Medical CenterCHA University School of MedicineSeongnam-siGyeonggi-doKorea Department of Pathology CHA Bundang Medical CenterCHA University School of MedicineSeongnam-siGyeo-nggi-doKorea CHA Future Medicine Research Institute CHA Bundang Medical CenterSeongnam-siGyeonggi-doKorea

We report a case of a patient with c-MET amplified hepato-cellular carcinoma (HCC) who had a dramatic response to cabozantinib despite being refractory to four previous lines of systemic therapy. The patient had previously received re-gorafenib plus nivolumab as first-line treatment, lenvatinib as second-line, sorafenib as third-line, and ipilimumab plus nivolumab as fourth-line treatment in sequence. However, all regimens showed early progression within 2 months. The pa-tient’s HCC was well-controlled, with a partial response (PR) of over 9 months after beginning cabozantinib treatment. Although there were mild adverse events such as diarrhea and elevated liver enzymes, they were tolerable. Next-gen-eration sequencing (NGS) of the patient’s previous surgical specimen indicated amplification of c-MET genes. Although it is well known that cabozantinib has excellent effectiveness for inhibiting c-MET at the preclinical level, to the best of our knowledge this is the first case of dramatic response to cabozantinib in a patient with advanced HCC with c-MET am-plification.

关键词： Hepatocellular carcinoma c-MET amplification Cabozantinib Dra-matic response Next-generation sequencing

Paclitaxel and curcumin co-bound albumin nanoparticles having antitumor potential to pancreatic cancer

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Asian Journal of Pharmaceutical Sciences 2016年第6期11卷 708-714页

作者： Bomi kim Changkyu Lee Eun Seong Lee beom Soo Shin Yu Seok Youn School of Pharmacy Sungkyunkwan University2066 Seobu-roJangan-guSuwonGyeonggi-do 16419Republic of Korea Division of Biotechnology The Catholic University of Korea43-1 Yeokgok 2-dongWonmi-guBucheon-siGyeonggi-do 14662Republic of Korea College of Pharmacy Catholic University of Daegu330 Geumrak 1-riHayang EupGyeongsan siGyeongbuk 38430Republic of Korea

Albumin nanoparticles are considered to be an effective way to load water-insoluble anticancer drugs and target tumors via the gp60-mediated pathway. Herein, we fabricated an albumin nanoparticle formulation for co-loading paclitaxel(PTX) and curcumin(CCM), both of which have prominent anticancer efficacy, via nanoparticle albumin-bound(NabTM) technology using high-pressure homogenization. The PTX/CCM co-bound albumin nanoparticles(PTX/CCM Alb-NPs) had a slightly greater particle size of ~250 nm than that of plain PTX AlbNPs and CCM Alb-NPs(~234 and ~134 nm, respectively), with spherical surface morphology and stable size maintenance. However, the zeta potential of PTX/CCM Alb-NPs(ca.-30 mV)was not significantly different from that of PTX or CCM Alb-NPs. The loaded PTX and CCM were released gradually from the PTX/CCM Alb-NPs over ~24 h(97.7 ± 1.7% and 76.2 ± 0.5%,respectively). Furthermore, PTX/CCM Alb-NPs appeared to be efficiently internalized into Mia Paca-2 cells and exhibited a 71% increased IC50 versus PTX Alb-NPs in terms of cytotoxicity to Mia Paca-2 cells. These results suggest that PTX/CCM Alb-NPs are a new potential anticancer agent for combination therapy.

关键词： Albumin Nanoparticles Paclitaxel Curcumin NabTM technology Anti-cancer agent

Molecular mechanisms of ZD1839 (Iressa)-induced apoptosis in human leukemic U937 cells

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Acta Pharmacologica Sinica 2007年第8期28卷 1205-1214页

作者： Dong-oh MOON Moon-ok kim Jae-dong LEE Yung-hyun CHOI Min-ki LEE gi-young kim Faculty of Applied Marine Science Cheju National UniversityJeju Special Self-Governing Province 690-756Republic of Korea Department of Microbiology Pusan National UniversityBusan 614-052Republic of Korea Department of Biochemistry Dongeui University College of Oriental MedicineBusan 614-052Republic of Korea Department of Internal Medicine Pusan National University College o MedicineBusan 602-739Republic of Korea

Aim:To investigate the molecular mechanisms of ZD1839-induced apoptosis inhuman leukemic U937 ***:The inhibition of human leukemic U937 cellgrowth was assessed by 3-（4,5-dimethyl-2-thiazolyl）-2,5-diphnyl-2H-tetrazolimbromide（MTT）assays,lactate dehydrogenase（LDH）release,and cell *** expression of anti- and pro-apoptotic proteins was detected byWestern blot ***:This study demonstrated that ZD 1839 inducedapoptosis in leukemic U937 cells by the downregulation of Bcl-2,caspase activa-tion and subsequent apoptotic *** with ZD 1839 and the caspase-3 inhibitor z-DEVD-fmk blocked apoptosis,indicating that caspase-3 activation isat least partially responsible for ZD1839-induced *** ectopic expres-sion of Bcl-2 attenuated caspase-3 activation,PARP cleavage,and subsequentindicators of apoptosis,including sub-G1DNA content and LDH *** indicate that the downregulation of Bcl-2 plays a major role in the initiationof ZD1839-induced apoptosis,and that the activation of a caspase cascade isinvolved in the execution of ***,ZD 1839 treatment triggeredthe activation of p38 mitogen-activated protein kinase（MAPK）and the down-regulation of c-Jun-N-terminal kinase（JNK）,extracellular signal-regulated kinase（ERK）and phosphatidyl inositol 3-kinase（PI3K）/*** inhibition of the ERKand PI3K/Akt pathways also significantly increased cellular ***:ZD 1839 activated caspase-3 and the inhibited Bcl-2 in human leukemic U937 cellsthrough the downregulation of the ERK and PI3K/Akt pathways.

关键词： ZD1839(Iressa) apoptosis caspase-3 Bcl-2 mitogen-activated protein kinases

High-performance solid-solution potassium-ion intercalation mechanism of multilayered turbostratic graphene nanosheets

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Journal of Energy Chemistry 2022年第4期31卷 814-823页

作者： Jiae Um Seung Uk Yoon Hoseong kim beom Sik Youn Hyoung-Joon Jin Hyung-Kyu Lim Young Soo Yun Program in Environmental and Polymer Engineering Inha Universityncheon 22212 South Korea Department of Polymer Science and Engineering Inha UniversityIncheon 22212South Korea Division of Chemical Engineering and Bioengineering Kangwon National University Chuncheon Gangwon-do 24341 South Korea KU-KIST Graduate School of Converging Science and Technologyea University 145 Anam-roSeongbuk-guSoul02841 South Korea Department of Integrative Energy Engineering 145 Anam-roSongbuk-guKorea UniversitySeoul 02841 South Korea

The solid-solution reaction between an alkali cation and an active host material is known as a singlephase redox mechanism,and it is typically accompanied by a continuous voltage *** is distinct from the typical alkali cation intercalation reaction at an equivalent site of the active host material,which exhibits a voltage ***,we report an unusual solid-solution potassium-ion intercalation mechanism with a low-voltage plateau capacity on multilayered turbostratic graphene nanosheets(T-GNSs).Despite the disordered graphitic structure with a broad range of d-spacings(3.65–4.18À),the T-GNSs showed a reversible plateau capacity of~200 m A h g^(-1),which is higher than that of a well-ordered graphite nanoplate(~120 m A h g^(-1)).In addition,a sloping capacity of~220 m A h g^(-1)was delivered with the plateau capacity,and higher rate capabilities,better reversibility,and a more stable cycling performance were confirmed on the turbostratic ***-principles calculations suggest that the multitudinous lattice domains of the T-GNSs contain diverse intercalation sites with strong binding energies,which could be the origin of the high-performance solid-solution potassium-ion intercalation behavior when the turbostratic graphene stacks have a d-spacing smaller than that of equilibrium potassium–graphite intercalation compounds(5.35À).

关键词： Turbostratic graphite Graphene nanosheet Defective carbon Anode Potassium-ion batteries

Experimental and computational optimization of Prussian blue analogues as high-performance cathodes for sodium-ion batteries:A review

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Journal of Energy Chemistry 2024年第6期93卷 627-662,I0015页

作者： Gwangeon Oh Junghoon kim Shivam Kansara Hyokyeong Kang Hun-gi Jung Yang-Kook Sun Jang-Yeon Hwang Department of Energy Engineering Hanyang UniversitySeoul 04763Republic of Korea Energy Storage Research Center Clean Energy Research DivisionKorea Institute of Science and TechnologySeoul 02792Republic of Korea Department of Energy Science Sungkyunkwan UniversitySuwon 16419Republic of Korea KIST-SKKU Carbon-Neutral Research Center Sungkyunkwan UniversitySuwon 16419Republic of Korea Department of Battery Engineering Hanyang UniversitySeoul 04763Republic of Korea

In this review,we discuss the electrochemical properties of Prussian blue(PB)for Na^(+)storage by combining structural engineering and electrolyte *** integrated experimental data and density functional theory(DFT)in sodium-ion battery(SIB)research to refine the atomic arrangements and crystal lattices and introduce substitutions and *** changes affect the lattice stability,intercalation,electronic and ionic conductivities,and electrochemical *** unraveled the intricate structure-electrochemical behavior relationship by combining experimental data with computational models,including first-principles *** holistic approach identified techniques for optimizing PB and Prussian blue analog(PBA)structu ral properties for *** also discuss the tuning of electrolytes by systematically adjusting their composition,concentration,and additives using a combination of molecular dynamics(MD)simulations and DFT *** review offers a comprehensive assessment of strategies for enhancing the electrochemical properties of PB and PBAs through structural engineering and electrolyte modifications,combining experimental insights with advanced computational simulations,and paving the way for next-generation energy storage systems.

关键词： Prussian blue analogs(PBAs) Sodium ion batteries(SIBs) Structural engineering Electrolyte modifications Experiments Density functional theory(DFT)

Nanomolar concentration of alpha-synuclein enhances dopaminergic neuronal survival via Akt pathway

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Neural Regeneration Research 2013年第35期8卷 3269-3274页

作者： Ji-Young kim beom Seok Jeon Han-Joon kim Tae-beom Ahn Department of Neurology Inje University Seoul Paik Hospital Department of Neurology College of Medicine Seoul National University Hospital Department of Neurology Kyung Hee University Medical Center

Although alpha-synuclein is generally thought to have a pathological role in Parkinson＇s disease, accumulative evidence exists that alpha-synuclein has a neuroprotective effect. The aim of this study was to evaluate the effect of extracellular alpha-synuclein on dopaminergic cell survival. We assessed cell viability using the 3-（4,5-dimethyt-thiazol-2-yt）-2,5-diphenyltertazolium bromide （MTT） assay both in undifferentiated SH-SY5Y （SHSY） cells and neuronally-differentiated SH-SY5Y （ndSHSY） cells after 24 hour treatment with monomeric alpha-synuclein at various concentrations （0 [control], 50, 100 nmol/L, 1 IJmol/L）. To determine whether cell viability assessed by MTT assay was affected by cell proliferation, 5-bromo-2＇-deoxyuridine （BrdU） incorporation assay was per- formed. Level of both Akt and phosphorylated Akt was measured using western blot method in ndSHSY cells with or without 24 hour alpha-synuclein treatment. Cell viability was increased in ndSHSY cells at the nanomolar concentration of alpha-synuclein, but not in SHSY cells. Proportion of BrdU-positive ndSHSY cells was decreased in alpha-synuclein-treated group compared with control group. Level of phosphorylated Akt in alpha-synuclein-treated group was higher compared with the control group. Our study shows that extracellular alpha-synuclein at nanomolar concentra- tion benefits dopaminergic cell survival via Akt pathway.

关键词： neural regeneration alpha-synuclein neuronal survival nanomolar extracellular phosphorylatedAkt SH-SY5Y cell neuronal differentiation proliferation dopaminergic 5-bromo-2'-deoxyuridine grants-supported paper neuroregeneration

Identification of Aristolactam Derivatives That Act as Inhibitors of Human Immunodeficiency Virus Type 1 Infection and Replication by Targeting Tat-Mediated Viral Transcription

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Virologica Sinica 2021年第2期36卷 254-263页

作者： Young Hyun Shin Chul Min Park Hong gi kim Dong-Eun kim Min Suk Choi Jeong-ah kim Byeong-Sun Choi Cheol-Hee Yoon Division of Viral Disease Research Center for Infectious Disease ResearchKorea National Institute of HealthHeungdeok-guCheongju-siShungbuk 28159Republic of Korea Center for Convergent Research of Emerging Virus Infection Korea Research Institute of Chemical TechnologyYuseong-guDaejeon 34114Republic of Korea

Despite the success of antiretroviral therapy(ART),efforts to develop new classes of antiviral agents have been hampered by the emergence of drug ***-indole-bearing aristolactams are compounds that have been isolated from various plants species and which show several clinically relevant effects,including anti-inflammatory,antiplatelet,and antimycobacterial ***,the effect of these compounds on human immunodeficiency virus type 1(HIV-1)infection has not yet been *** this study,we discovered an aristolactam derivative bearing dibenzo[cd,f]indol-4(5 H)-one that had a potent anti-HIV-1 effect.A structure-activity relationship(SAR)study using nine synthetic derivatives of aristolactam identified the differing effects of residue substitutions on the inhibition of HIV-1 infection and cell *** the compounds tested,1,2,8,9-tetramethoxy-5-(2-(piperidin-1-yl)ethyl)-dibenzo[cd,f]indol-4(5 H)-one(Compound 2)exhibited the most potent activity by inhibiting HIV-1 infection with a half-maximal inhibitory concentration(IC50)of 1.03 lmol/L and a half-maximal cytotoxic concentration(CC50)of 16.91 lmol/L(selectivity index,16.45).The inhibitory effect of the compounds on HIV-1 infection was linked to inhibition of the viral replication ***-of-action studies showed that the aristolactam derivatives did not affect reverse transcription or integration;instead,they specifically inhibited Tat-mediated viral *** together,these findings show that several aristolactam derivatives impaired HIV-1 infection by inhibiting the activity of Tat-mediated viral transcription,and suggest that these derivatives could be antiviral drug candidates.

关键词： Human immunodeficiency virus type 1(HIV-1) Aristolactam Antiviral activity HIV-1 transcription

Surface characteristics of HA coated Ti-Hf binary alloys after nanotube formation

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中国有色金属学会会刊：英文版 2009年第4期19卷 852-856页

作者： Yong-Hoon JEONG Won-gi kim Geun-Hyeong PARK Han-Cheol CHOE Yeong-Mu KO Department of Dental Materials & Research Center of Nano-Interface Activation for Biomaterials College of DentistryChosun University Research Center for Oral Disease Regulation of the Aged College of DentistryChosun University

Ti-Hf binary alloys contained 10%,20%,30% and 40%(mass fraction)Hf were manufactured in the vacuum furnace *** then,specimens were homogenized for 24 h at 1 000 ℃ in argon *** formation of oxide nanotubes was conducted by anodic oxidation on the Ti-Hf alloy in 1 mol/L H3PO4 electrolytes containing small amounts of NaF at room *** hydroxyapatite(HA) coating made of tooth ash prepared by electron-beam physical vapor deposition(EB-PVD) *** corrosion behaviors of the specimens were examined through potentiodynamic test in 0.9% NaCl solution by *** microstructures of the alloys were examined by field emission scanning electron microscopy(FE-SEM) and x-ray diffractometer(XRD).It was observed that the lamellar structure translated to needle-like structure with Hf *** formed and HA coated Ti-xHf alloys had a good corrosion resistance.

关键词：二元合金 HA涂层纳米管表面特性管形 0.9%NaCl溶液物理气相沉积铪

Multi-millijoule terahertz emission from laser- wakefield-accelerated electrons

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Light(Science & Applications) 2023年第2期12卷 248-258页

作者： Taegyu Pak Mohammad Rezaei-Pandari Sang beom kim Geonwoo Lee Dae Hee Wi Calin loan Hojbota Mohammad Mirzaie Hyeongmun kim Jae Hee Sung Seong Ku Lee Chul Kang Ki-Yong kim Center for Relativistic Laser Science Institute for Basic ScienceGwangju 61005Korea Department of Physics and Photon Science Gwangju Institute of Science and Technology(GIST)Gwangju 61005Korea Laser and Plasma Research Institute Shahid Beheshti UniversityTehranIran Advanced Photonics Research Institute GISTGwangju 61005Korea Institute for Research in Electronics and Applied Physics and Department of Physics University of MarylandCollege ParkMaryland 20742USA

High-power terahertz radiation was observed to be emitted from a gas jet irradiated by 100-terawatt-class laser pulses in the laser-wakefield acceleration of *** emitted terahertz radiation was characterized in terms of its spectrum,polarization,and energy dependence on the accompanying electron bunch energy and charge under various gas target *** a nitrogen target,more than 4 mJ of energy Was produced at<10 THz with a laser-to-terahertz conversion efficiency of~0.15%.Such strong terahertz radiation is hypothesized to be produced from plasma electrons accelerated by the ponderomotive force of the laser and the plasma wakefelds on the time scale of the laser pulse duration and plasma *** model is examined with analytic calculations and particle-in-cell simulations to better understand the generation mechanism of high-energy terahertz radiation in laser-wakefield acceleration.

关键词： laser polarization acceleration