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The role of MDM2 and MDM4 in breast cancer development and prevention

Journal of Molecular Cell Biology 2017年第1期9卷 53-61页

作者： Sue Haupt Reshma Vijayakumaran Panimaya Jeffreena Miranda Andrew Burgess elgene lim Ygal Haup Tumour Suppression Laboratory Peter MacCallum Cancer Centre Melbourne 3000 Australia Sir Peter MacCallum Department of Oncology The University of Melbourne Melbourne 3000 Australia The Kinghorn Cancer Centre Garvan Institute of Medical Research Sydney New South Wales 2010 Australia St. Vincent's Clinical School Faculty of Medicine University of New South Wales Sydney New South Wales 2010 Australia Department of Pathology The University of Melbourne Parkville Victoria 3010 Australia Department of Biochemistry and Molecular Biology Monash University Clayton Australia

The major cause of death from breast cancer is not the primary turnout, but relapsing, drug-resistant, metastatic disease. Identifying factors that contribute to aggressive cancer offers important leads for therapy. Inherent defence against carcinogens depends on the individual molecular make-up of each person. Important molecular determinants of these responses are under the control of the mouse double minute （MDM） family： comprised of the proteins MDM2 and MDM4. In normal, healthy adult cells, the MDM family functions to critically regulate measured, cellular responses to stress and subsequent recovery. Proper function of the MDM family is vital for normal breast development, but also for preserving genomic fidelity. The MDM family members are best characterized for their negative regulation of the major tumour suppressor p53 to modulate stress responses. Their impact on other cellular regulators is emerging. Inappropriately elevated protein levels of the MDM family are highly associated with an increased risk of cancer incidence. Exploration of the MDM family members as cancer therapeutic targets is relerant for designing tailored anti-cancer treatments, but successful approaches must strategically consider the impact on both the target cancer and adjacent healthy ceils and tissues. This review focuses on recent findings pertaining to the role of the MDM family in normal and malignant breast cells.

关键词： MDM2 MDM4 TP53 p53 breast cancer

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Triple combination targeting PI3K,ER,and CDK4/6 inhibits growth of ER-positive breast cancer resistant to fulvestrant and CDK4/6 or PI3K inhibitor

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Cancer Communications 2023年第6期43卷 720-725页

作者： Mikkel G.Terp Martina Tuttolomondo Neil Portman Sidse Ehmsen Lene E.Johansen Martin Bak elgene lim Henrik J.Ditzel Department of Cancer and Inflammation Research Institute of Molecular MedicineUniversity of Southern DenmarkOdenseDenmark Garvan Institute of Medical Research DarlinghurstSydneyNew SouthWalesAustralia St.Vincent’s Clinical School Faculty of MedicineUniversity of New SouthWales SydneySydneyNew South WalesAustralia Department of Oncology Institute of Clinical ResearchOdense University HospitalOdenseDenmark Department of Pathology Sydvestjysk SygehusEsbjergDenmark Academy of Geriatric Cancer Research(AgeCare) Odense University HospitalOdenseDenmark

Dear Editor,Despite the improved outcome of advanced estrogen receptor-positive(ER+)breast cancer patients treated with endocrine therapy in combination with either a cyclindependent kinase 4/6 inhibitor(CDK4/6i)or a phosphoinositide 3-kinase inhibitor(PI3Ki),the disease will eventually progress,and the optimal treatment strategy upon progression remains undefined[1-4].To address this,we developed MCF-7-and T47D-derived PIK3CAmutated breast cancer cell lines[5]resistant to combined CDK4/6i palbociclib and fulvestrant(MPF-R and TPFR)or combined PI3Ki alpelisib and fulvestrant(MAF-R and TAF-R),respectively(Supplementary Materials and Methods).Drug-sensitive isogenic cells(M-S and T-S)grown in parallel with MPF-R and TPF-R cells and the original MCF-7/S0.5 and T47D cells were analyzed for comparison.

关键词： PIK3CA breast cancer

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Single-cell and spatial omics:exploring hypothalamic heterogeneity

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Neural Regeneration Research 2025年第6期20卷 1525-1540页

作者： Muhammad Junaid Eun Jeong Lee Su Bin lim Department of Biochemistry&Molecular Biology Ajou University School of MedicineSuwonSouth Korea Department of Biomedical Sciences Graduate School of Ajou UniversitySuwonSouth Korea Department of Brain Science Ajou University School of MedicineSuwonSouth Korea

Elucidating the complex dynamic cellular organization in the hypothalamus is critical for understanding its role in coordinating fundamental body functions. Over the past decade, single-cell and spatial omics technologies have significantly evolved, overcoming initial technical challenges in capturing and analyzing individual cells. These high-throughput omics technologies now offer a remarkable opportunity to comprehend the complex spatiotemporal patterns of transcriptional diversity and cell-type characteristics across the entire hypothalamus. Current single-cell and single-nucleus RNA sequencing methods comprehensively quantify gene expression by exploring distinct phenotypes across various subregions of the hypothalamus. However, single-cell/single-nucleus RNA sequencing requires isolating the cell/nuclei from the tissue, potentially resulting in the loss of spatial information concerning neuronal networks. Spatial transcriptomics methods, by bypassing the cell dissociation, can elucidate the intricate spatial organization of neural networks through their imaging and sequencing technologies. In this review, we highlight the applicative value of single-cell and spatial transcriptomics in exploring the complex molecular-genetic diversity of hypothalamic cell types, driven by recent high-throughput achievements.

关键词： cellular diversity hypothalamus multi-omics single-cell transcriptomics spatial transcriptomics

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Characterizations of organic compounds in diesel exhaust particulates

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Journal of Environmental Sciences 2015年第8期27卷 171-183页

作者： Jaehyun lim Cheolsoo lim Sangkyun Kim Jihyung Hong Division of Global Environment Research National Institute of Environmental Research Department of Climate and Air Quality Research National Institute of Environmental Research

To characterize how the speed and load of a medium-duty diesel engine affected the organic compounds in diesel particle matter（PM） below 1 μm, four driving conditions were examined. At all four driving conditions, concentration of identifiable organic compounds in PM ultrafine（34–94 nm） and accumulation（94–1000 nm） modes ranged from 2.9 to 5.7 μg/m3 and 9.5 to 16.4 μg/m3, respectively. As a function of driving conditions, the non-oxygencontaining organics exhibited a reversed concentration trend to the oxygen-containing organics. The identified organic compounds were classified into eleven classes： alkanes,alkenes, alkynes, aromatic hydrocarbons, carboxylic acids, esters, ketones, alcohols, ethers,nitrogen-containing compounds, and sulfur-containing compounds. At all driving conditions,alkane class consistently showed the highest concentration（8.3 to 18.0 μg/m3） followed by carboxylic acid, esters, ketones and alcohols. Twelve polycyclic aromatic hydrocarbons（PAHs）were identified with a total concentration ranging from 37.9 to 174.8 ng/m3. In addition, nine nitrogen-containing polycyclic aromatic compounds（NPACs） were identified with a total concentration ranging from 7.0 to 10.3 ng/m3. The most abundant PAH（phenanthrene）and NPACs（7,8-benzoquinoline and 3-nitrophenanthrene） comprise a similar molecular（3 aromatic-ring） structure under the highest engine speed and engine load.

关键词： Diesel particle matter Organic compounds Polycyclic aromatic hydrocarbons Nitrogen-containing polycyclic aromatic compounds

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Landau damping of twisted waves in Cairns distribution with anisotropic temperature

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Plasma Science and Technology 2021年第8期23卷 18-28页

作者： Sunggeun LEE Hankwon lim School of Energy and Chemical Engineering UNIST50UNIST-gilEonyang-eupUlju-gunUlsan 44919Republic of Korea

The consideration of orbital angular momentum of an electric field(twisted mode)is applied to the kinetic theory of *** linearized Vlasov–Poisson equation is solved for the anisotropic thermal distributed bi-Maxwellian and Cairns distributions of electrons to obtain the damping rates of twisted *** dispersion relation and Landau damping of Langmuir twisted modes are *** presence of twisted modes opens up two more possibilities in Landau damping and dispersion *** may generate a mixture with ion sound *** seems to play the role of a control parameter of Landau damping.

关键词： Landau damping Cairns distribution function anisotropic

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Emissions of Er3+ and Yb3+ co-doped SrZrO3 nanocrystals under near-infrared and near-ultraviolet excitations

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Journal of Advanced Ceramics 2020年第4期9卷 413-423页

作者： Hyeontae lim Juyeong lim Soyoung Jang Y.S.Lee Department of Physics Soongsil UniversitySeoul06978Republic of Korea

In this study,the upconversion(UC)emissions of Er3+and Yb3+co-doped SrZrO3 nanocrystals(NCs)were investigated in terms of the thermal annealing temperature and concentration of Er3+ions and compared with the emissions under a near-ultraviolet(near-UV)*** NCs were synthesized by the combustion method,and the as-synthesized NCs were post-annealed at high *** X-ray diffraction patterns revealed that the grain sizes and crystallinity degrees of the samples increased with increasing annealing *** photoluminescence spectra of our samples exhibited strong green and very weak red emissions with the near-UV excitation,originating from the f-f transitions in the Er3+***,under near-infrared(near-IR)excitation,we identified sizable visible emissions at 525,547,and 660 nm in our NCs,which indicated that the UC process successfully occurred in our *** UC emissions were maximized in the NCs with an Er3+concentration of 0.02 and thermal annealing at 1000°*** found that the intensity ratios of red to green emissions increased with increasing annealing *** discussed the differences in the emissions between near-UV and near-IR excitations.

关键词： Er3+and Yb3+co-doped SrZrO3 upconversion downshifting nanocrystals combustion method annealing temperature

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On p^(j)-rank of Even K-groups of Rings of Integers

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Acta Mathematica Sinica,English Series 2024年第10期40卷 2481-2496页

作者： Meng Fai lim School of Mathematics and Statistics&Hubei Key Laboratory of Mathematical Sciences Central China Normal UniversityWuhan 430079P.R.China

Let L/F be a finite Galois extension of number fields of degree n and let p be a prime which does not divide *** shall study the p^(j)-rank of K_(2i)(O_(L))via its Galois module structure following the approaches of Iwasawa and Komatsu–*** the way,we generalize previous observations of Browkin,Wu and Zhou on K_(2)-groups to higher even *** also give examples to illustrate our ***,we apply our discussion to refine a result of Kitajima pertaining to the p-rank of even K-groups in the cyclotomic Z_(l)-extension,where l≠p.

关键词： p^(j)-rank even K-groups rings of integers

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Cydodextrin conjugated ferritin nanocages reduce intracellular cholesterol level in foam cells

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Nano Research 2019年第12期12卷 2925-2932页

作者： Samyukta Ravishankar Sierin lim School of Chemical and Biomedical Engineering Nanyang Technological University70 Nanyang DriveBlk N1.3Singapore 637457Singapore NTU-Northwestem Institute for Nanomedicine Nanyang Technological University50 Nanyang DriveBlk N3.1Singapore 637553Singapore

Accumulation of lipid-laden macrophages(foam cells)is characteristic of atherosclerosis developme nt in the arterial *** nano cages have been found to passively accumulate in the atherosclerotic *** has been actively investigated as a carrier for contrast agents in atherosclerosis diag no *** dem on strate the pote ntial of ferritin as a carrier for therapeutic molecules to mediate cholesterol reducti on from foam *** molecules are chemically conjugated to the ferritin anocages surface or encapsulated within the nanocages using metal co-loadi ng *** cyclodextrin-conjugated ferriti n has nano molar affinity to cholesterol *** of foam cells with the conjugates shows decreased levels of intracellular accumulated *** preferential localization of ferritin to foam cells is due to transferrin receptor-mediated endocytosis *** findings show that ferritin nanocages as carriers localize cyclodextrin molecules to foam cells which mediate intracellular cholesterol reductio n,thus highlight!ng its potential use as a therapeutic agent.

关键词： cyclodextrin ferritin protein nanocages cholesterol sequestration foam cells

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Architecture for mobile group communication in campus environment

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Frontiers of Computer Science 2013年第4期7卷 505-513页

作者： Yujin lim Sanghyun AHN Department of Information Media University of Suwon Hwaseong 445-743 Korea School of Computer Science University of Seoul Seoul 130-743 Korea

The demand for group communication using smart devices in campus environment is increasing rapidly. In this paper, we design an architecture for a mobile group communication system （MGCS） on campus by using Wi-Fi networks and smart devices. The architecture is composed of a web-based system and a smart device based mobile system. Through the systems, users on campus create community/mobile group, maintain dynamic group membership, and reliably deliver the message to other users. We use the common features of many smart devices to develop a prototype that works on off-the-shelf hardware. In the experimental section, we demonstrate our system using various real scenarios which can occur in university campuses.

关键词： smart campus smartphone location tracking,mobile community

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Polarity control of carrier injection for nanowire feedback field-effect transistors

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Nano Research 2019年第10期12卷 2509-2514页

作者： Doohyeok lim Sangsig Kim Department of Electrical Engineering Korea University145 Anam-roSeongbuk-guSeoul 02841Republic of Korea

We present polarity control of the carrier injection for a feedback field-effect transistor(FBFET)with a selectively thinned p^+-i-n^+Si nanowire(SiNW)channel and two separate *** SiNW FBFET can be reconfigured in the p-or n-channel operation modes via simple control of electric *** two separate gates induce potential barriers in the SiNW channel for selective control of the carrier *** contrast to previously reported rec on figurable tran sistors,our tran sistor features symmetry of the electrical characteristics for the p-and n-cha nnel operation ***-feedback operation of the SiNW FBFET provides superior switching characteristics for the p-and n-type 8nfigurations,including the on/off ratios(~10^5)and subthreshold swings(1.36-1.78 mV/dec).This novel tran sistor is a promising can didate for reconfigurable electro nics.

关键词： silicon nanowire reconfigurable transistor positive-feedback loop separate gate

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