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Exosome secretion from hypoxic cancer cells reshapes the tumor microenvironment and mediates drug resistance

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Cancer Drug Resistance 2022年第3期5卷 577-594页

作者： kenneth k.w.to william C.S.Cho School of Pharmacy Faculty of MedicineThe Chinese University of Hong KongHong Kong SARChina Department of Clinical Oncology Queen Elizabeth HospitalHong Kong SARChina

Hypoxia is a common phenomenon in solid tumors as the poorly organized tumor vasculature cannot fulfill the increasing oxygen demand of rapidly expanding *** hypoxia,tumor cells reshape their microenvironment to sustain survival,promote metastasis,and develop resistance to *** are extracellular vesicles secreted by most eukaryotic cells,including tumor *** are enriched with a selective collection of nucleic acids and proteins from the originating cells to mediate cell-to-cell *** evidence suggests that exosomes derived from tumor cells play critical roles in modulating the tumor microenvironment(TME).Hypoxia is known to stimulate the secretion of exosomes from tumor cells,thereby promoting intercellular communication of hypoxic tumors with the surrounding stromal ***-mediated signaling pathways under hypoxic conditions have been reported to cause angiogenesis,invasion,metastasis,drug resistance,and immune ***,the programmed cell death ligand-1(PD-L1)has been reported to reside as a transmembrane protein in tumor *** PD-L1 was shown to suppress T cell effector function in the TME and cause drug resistance to immune checkpoint *** review provides an update about the pivotal role of tumor-derived exosomes in drug resistance to chemotherapy and immunotherapy,particularly under hypoxic *** strategies that target the exosomes in the hypoxic TME to enhance the antitumor efficacy are discussed.

关键词： Hypoxia drug resistance exosome tumor microenvironment immunotherapy non-coding RNA

Olmutinib(HM61713) reversed multidrug resistance by inhibiting the activity of ATPbinding cassette subfamily G member 2 in vitro and in vivo

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Acta Pharmaceutica Sinica B 2018年第4期8卷 563-574页

作者： Zhiqiang Zhang Xiaoran Guo kenneth k.w.to Zhen Chen Xiaona Fang Min Luo Chunling Ma Jianhua Xu Shirong Yan Liwu Fu Sun Yat-sen University Cancer Center State key Laboratory of Oncology in South China Collaborative Innovation Center for Cancer Medicine School of Pharmacy Fujian Medical University Hubei University of Medicine School of Pharmacy Faculty of Medicinethe Chinese University of Hong Kong

Overexpressing of ATP-binding cassette(ABC) transporters is the essential cause of multidrug resistance(MDR), which is a significant hurdle to the success of chemotherapy in many ***, inhibiting the activity of ABC transporters may be a logical approach to circumvent *** is an epidermal growth factor receptor(EGFR) tyrosine kinase inhibitor(TkI), which has been approved in South korea for advanced EGFR T790 M-positive non-small cell lung cancer(NSCLC). Here,we found that olmutinib significantly increased the sensitivity of chemotherapy drug in ABCG2-overexpressing cells. Furthermore, olmutinib could also increase the retention of doxorubicin(DOX) and rhodamine 123(Rho 123) in ABC transporter subfamily G member 2(ABCG2)-overexpressing cells. In addition, olmutinib was found to stimulate ATPase activity and inhibit photolabeling of ABCG2 with [^(125) I]-iodoarylazidoprazosin(IAAP). However, olmutinib neither altered ABCG2 expression at protein and m RNA levels nor blocked EGFR, Her-2 downstream signaling of AkT and ERk. Importantly,olmutinib enhanced the efficacy of topotecan on the inhibition of S1-MI-80 cell xenograft growth. All the results suggest that olmutinib reverses ABCG2-mediated MDR by binding to ATP bind site of ABCG2 and increasing intracellular chemotherapeutic drug accumulation. Our findings encouraged to further clinical investigation on combination therapy of olmutinib with conventional chemotherapeutic drugs in ABCG2-overexpressing cancer patients.

关键词： Olmutinib ABCG2 Multidrug resistance Tyrosine kinase inhibitor Chemotherapy ATPase

Reversal of P-gp-mediated Multidrug Resistance of Anticancer Agents by Herbal Components

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Reversal of P-gp-mediated Multidrug Resistance of Anticancer...

Smart mid-infrared metasurface microspectrometer gas sensing system

第十四届全国中药和天然药物学术研讨会

作者： Chun Yin kenneth k.w.to Stella Chai Yang Ye Ge Lin School of Biomedical Sciences The Chinese University of Hong Kong Joint Research Laboratory of Promoting Globalization of Traditional Chinese Medicines between Shanghai Institute of Materia Medica Chinese Academy of Sciences and The Chinese University of Hong Kong School of Pharmacy The Chinese University of Hong Kong State key Laboratory of Drug Research and Natural Products Chemistry Department Shanghai Institute of Materia MedicaChinese Academy of Sciences

＜正＞One of the major obstacles to successful anticancer chemotherapy is multidrug resistance（MDR）.The overexpression of ATP-binding cassette（ABC）transporters to pump anticancer drugs out of resistant cancer cells can cause MDR.P-glycoprotein（P-gp）is the most extensively studied ABC transporter conferring *** present study aimed to demonstrate

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来源： cnki会议评论

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Microsystems & Nanoengineering 2024年第3期10卷 273-281页

作者： Jiajun Meng Sivacarendran Balendhran Ylias Sabri Suresh k.Bhargava kenneth B.Crozier School of Physics University of MelbourneVictoriaAustralia Australian Research Council(ARC)Centre of Excellence for Transformative Meta-Optical Systems(TMOS) University of MelbourneVictoriaAustralia Centre for Advanced Materials&Industrial Chemistry(CAMIC) STEM collegeRMIT UniversityVictoriaAustralia Department of Electrical and Electronic Engineering University of MelbourneVictoriaAustralia

Smart,low-cost and portable gas sensors are highly desired due to the importance of air quality monitoring for environmental and defense-related ***,electrochemical and nondispersive infrared(IR)gas sensors are designed to detect a single specific *** IR spectroscopy-based sensors provide superior performance,their deployment is limited due to their large size and high *** this study,a smart,low-cost,multigas sensing system is demonstrated consisting of a mid-infrared microspectrometer and a machine learning *** microspectrometer is a metasurface filter array integrated with a commercial IR camera that is consumable-free,compact(~1 cm^(3))and lightweight(~1 g).The machine learning algorithm is trained to analyze the data from the microspectrometer and predict the gases *** system detects the greenhouse gases carbon dioxide and methane at concentrations ranging from 10 to 100%with 100%*** also detects hazardous gases at low concentrations with an accuracy of 98.4%.Ammonia can be detected at a concentration of 100 ***,methyl-ethyl-ketone can be detected at its permissible exposure limit(200 ppm);this concentration is considered low and *** study demonstrates the viability of using machine learning with IR spectroscopy to provide a smart and low-cost multigas sensing platform.

关键词： Smart gases system

well-Posedness of Stochastic Continuity Equations on Riemannian Manifolds

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Chinese Annals of Mathematics,Series B 2024年第1期45卷 81-122页

作者： Luca GALIMBERTI kenneth H.kARLSEN Department of Mathematical Sciences NTNU Norwegian University of Science and TechnologyN-7491 TrondheimNorway Department of mathematics University of OsloP.O.Box 1053BlindernN-0316 OsloNorway

The authors analyze continuity equations with Stratonovich stochasticity,■ρ+divh[ρo(u(t,x)+∑_(i=1)^(N)a_(i)(x)w_(i)(t))]=0defined on a smooth closed Riemannian manifold M with metric *** velocity field u is perturbed by Gaussian noise terms wi(t),:wN(t)driven by smooth spatially dependent vector fields a1(x),...,aN(x)on *** velocity u belongs to L_(t)^(1)w_(x)^(1,2)with divh u bounded in Lf,for p>d+2,where d is the dimension of M(they do not assume div_(h) u∈L_(t,x)^(∞)).For carefully chosen noise vector fields ai(and the number N of them),they show that the initial-value problem is well-posed in the class of weak L^(2) solutions,although the problem can be ill-posed in the deterministic case because of concentration *** proof of this“regularization by noise”result is based on a L^(2) estimate,which is obtained by a duality method,and a weak compactness argument.

关键词： Stochastic continuity equation Riemannian manifold Hyperbolic equa-tion Non-smooth velocity field weak solution Existence Uniqueness

Methodological considerations of priming repetitive transcranial magnetic stimulation protocols in clinical populations

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General Psychiatry 2024年第1期37卷 173-176页

作者： Jack Jiaqi Zhang Zhongfei Bai kenneth N k Fong Department of Rehabilitation Sciences The Hong Kong Polytechnic UniversityHong KongChina Shanghai YangZhi Rehabilitation Hospital(Shanghai Sunshine Rehabilitation Centre) School of MedicineTongji UniversityShanghaiChina

INTRODUCTION Repetitive transcranial magnetic stimulation(rTMS)is a neuroplasticity-enhancing technique that modifies brain responsiveness to various therapeutic modalities in clinical psychiatric and neurological applications. Furthermore,its effect can be attributed to long-term potentiation(LTP)or longterm depression(LTD)-like ***,responsiveness to rTMS is largely variable in healthy and pathological brains and is mediated by complex biological *** refers to a higher-order plasticity mechanism in which the direction and magnitude of synaptic plasticity are modified by prior neuronal activity and is believed to be a significant factor leading to the response variability of rTMs.

关键词： stimulation clinical transcranial

Surgical cystogastrostomy: Is it still worthwhile?

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world Journal of Gastroenterology 2024年第17期30卷 2298-2301页

作者： kin Pan Au kenneth Siu Ho Chok Department of Surgery Queen Mary HospitalThe University of Hong KongHong Kong 999077China Department of Surgery The Chinese University of Hong KongHong Kong 999077China

The article by ker et al explores the treatment of peripancreatic fluid collection(PFC).The use of percutaneous drainage,endoscopy,and surgery for managing PFC are *** drainage is noted for its low risk profile,while endoscopic cystogastrostomy is more effective due to the wider orifice of the metallic *** cystogastrostomy is a definitive treatment with a reduced need for reintervention,especially for cases with extensive collections and significant *** choice of treatment modality should be tailored to individual patient characteristics and disease factors,considering the expertise available.

关键词： Endoscopic cystgastrostomy Surgical cystgastrostomy Pancreatitis Pancreatic necrosis Peripancreatic collection

Biophotoelectrochemistry:An emerging frontier for channeling photoelectric effect into darkness zone of soils and sediments

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Pedosphere 2024年第1期34卷 5-8页

作者： Jie YE Shungui ZHOU kenneth H.NEALSON Christopher RENSING Fujian Provincial key Laboratory of Soil Environmental Health and Regulation College of Resources and EnvironmentFujian Agriculture and Forestry UniversityFuzhou 350002China Department of Earth Science University of Southern CaliforniaLos Angeles CA 90007USA

Solar energy captured by photosynthetic plants in the photic zone is recognized as the main driver for the formation of organic matter utilized by soil communities. However, the contribution of organic transformation to the linkage of solar energy and microbial metabolism of soils is reduced when the vadose zone is saturated. In contrast to the conventional biophotoelectrochemistry via photosynthesis with phytoplankton during the periodic saturation of soils, recent studies suggest that non-phototrophic microorganisms in soils and sediments are able to conduct light-dependent metabolism to sustain their functionality with photosensitizers under illumination. These interactions and processes utilize long-distance electron transfer networks to interconnect diverse electron transfer chains that channel photoexcited electrons into the opaque zone for soil communities. Such an emerging process not only allows for a better understanding of biogeochemical processes such as soil carbon sequestration and mitigation, but also shows great potential for environmental treatment such as the bioremediation of contaminated soils. Therefore, we suggest that biophotoelectrochemistry via photoelectric effect can have significant, heretofore unappreciated, theoretical and practical values.

关键词： soils soil metabolism

Bile acid signaling in the regulation of whole body metabolic and immunological homeostasis

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Science China(Life Sciences) 2024年第5期67卷 865-878页

作者： wei Jia Yitao Li kenneth C.P.Cheung Xiaojiao Zheng School of Chinese Medicine Hong Kong Baptist UniversityHong KongChina Center for Translational Medicine and Shanghai key Laboratory of Diabetes Mellitus Shanghai Sixth People's Hospital Affiliated to Shanghai JiaoTong University School of MedicineShanghai 200233China

Bile acids(BAs)play a crucial role in nutrient absorption and act as key regulators of lipid and glucose metabolism and immune *** the enterohepatic circulation,BAs are synthesized,metabolized,and reabsorbed,with a portion entering the vascular circulation and distributing *** allows BAs to interact with receptors in all major organs,leading to organ-organ interactions that regulate both local and global metabolic processes,as well as the immune *** review focuses on the whole-body effects of BA-mediated metabolic and immunological regulation,including in the brain,heart,liver,intestine,eyes,skin,adipose tissue,and *** BA synthesis and receptor signaling is a promising strategy for the development of novel therapies for various diseases throughout the body.

关键词： bile acid whole body metabolism immunity