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Transdermal nanolipoplex simultaneously inhibits subcutaneous melanoma growth and suppresses systemically metastatic melanoma by activating host immunity

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Nanomedicine: Nanotechnology, Biology, and Medicine 2023年 47卷 102628-102628页

作者： Chen, Chia-Hung Weng, Tzu-Han Chuang, Cheng-Hsun Huang, Kai-Yao Huang, Sih-Cheng Chen, Pin-Rong Huang, Hsiao-Hsuan Huang, Ling-Ya Shen, Pei-Chun Chuang, Po-Ya Huang, Hsiao-Yen Wu, Yi-Syuan Chang, Hao-Chiun Weng, Shun-Long Liao, Kuang-Wen Department of Medical Research Hsinchu MacKay Memorial Hospital Hsinchu City30071 Taiwan Dependent of Medical Education MacKay Memorial Hospital Taipei10449 Taiwan Institute of Molecular Medicine and Bioengineering National Yang Ming Chiao Tung University Hsinchu City30068 Taiwan Department of Biological Science and Technology National Yang Ming Chiao Tung University Hsinchu City30068 Taiwan Industrial Development Graduate Program of College of Biological Science and Technology National Yang Ming Chiao Tung University Hsinchu City30068 Taiwan Institute of Bioinformatics and Systems Biology National Yang Ming Chiao Tung University Hsinchu City30068 Taiwan Department of Medicine MacKay Medical College New Taipei City25245 Taiwan Department of Obstetrics and Gynecology Hsinchu MacKay Memorial Hospital Hsinchu City30071 Taiwan MacKay Junior College of Medicine Nursing and Management Taipei City11260 Taiwan Drug Development and Value Creation Research Center College of Dental Medicine Kaohsiung Medical University School of Dentistry Graduate Institute of Medicine College of Medicine Center for Cancer Research Kaohsiung Medical University Kaohsiung City80708 Taiwan Center for Intelligent Drug Systems and Smart Bio-devices National Yang Ming Chiao Tung University Hsinchu City30068 Taiwan Department of Biotechnology and Bioindustry Sciences National Cheng Kung University Tainan City70101 Taiwan Ph.D. Degree Program of Biomedical Science and Engineering National Yang Ming Chiao Tung University Hsinchu City30068 Taiwan

Benefit for clinical melanoma treatments, the transdermal neoadjuvant therapy could reduce surgery region and increase immunotherapy efficacy. Using lipoplex (Lipo-PEG-PEI-complex, LPPC) encapsulated doxorubicin (dOX) and carrying CpG oligodeoxynucleotide;the transdermally administered nano-liposomal drug complex (LPPC-dOX-CpG) would have high cytotoxicity and immunostimulatory activity to suppress systemic metastasis of melanoma. LPPC-dOX-CpG dramatically suppressed subcutaneous melanoma growth by inducing tumor cell apoptosis and recruiting immune cells into the tumor area. Animal studies further showed that the colonization and growth of spontaneously metastatic melanoma cells in the liver and lung were suppressed by transdermal LPPC-dOX-CpG. Furthermore, NGS analysis revealed IFN-γ and NF-κB pathways were triggered to recruit and activate the antigen-presenting-cells and effecter cells, which could activate the anti-tumor responses as the major mechanism responsible for the therapeutic effect of LPPC-dOX-CpG. Finally, we have successfully proved transdermal LPPC-dOX-CpG as a promising penetrative carrier to activate systemic anti-tumor immunity against subcutaneous and metastatic tumor. © 2022

关键词： Tumors

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HER2 amplification in colorectal cancer with brain metastasis: A propensity score matching study

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European journal of cancer (Oxford, England : 1990) 2023年 181卷 62-69页

作者： Po-Chuan Chen Yu-Min Yeh Chun-Ting Chu Pei-Fang Su Pin-Hsuan Chiu Bo-Wen Lin Shang-Hung Chen Peng-Chan Lin Chung-Ta Lee Helen H W Chen Chien-Chin Chen Division of Colorectal Surgery Department of Surgery National Cheng Kung University Hospital College of Medicine National Cheng Kung University Tainan 704 Taiwan. Department of Oncology National Cheng Kung University Hospital College of Medicine National Cheng Kung University Tainan 704 Taiwan. Division of Colorectal Surgery Department of Surgery Ditmanson Medical Foundation Chia-Yi Christian Hospital Chiayi 600 Taiwan. Department of Statistics National Cheng Kung University Tainan 701 Taiwan. The Center of Quantitative Sciences Clinical Medicine Research Center National Cheng Kung University Hospital Tainan 704 Taiwan. Department of Oncology National Cheng Kung University Hospital College of Medicine National Cheng Kung University Tainan 704 Taiwan National Institute of Cancer Research National Health Research Institute Tainan 704 Taiwan. Department of Genomic Medicine National Cheng Kung University Hospital College of Medicine National Cheng Kung University Tainan 704 Taiwan Department of Computer Science and Information Engineering College of Electrical Engineering and Computer Science National Cheng Kung University Tainan 704 Taiwan. Department of Pathology National Cheng Kung University Hospital College of Medicine National Cheng Kung University Tainan 704 Taiwan. Department of Oncology National Cheng Kung University Hospital College of Medicine National Cheng Kung University Tainan 704 Taiwan. Electronic address: helen@mail.ncku.edu.tw. Department of Pathology Ditmanson Medical Foundation Chia-Yi Christian Hospital Chiayi 600 Taiwan Department of Cosmetic Science Chia Nan University of Pharmacy and Science Tainan 717 Taiwan Department of Biotechnology and Bioindustry Sciences College of Bioscience and Biotechnology National Cheng Kung University Tainan 701 Taiwan Ph.D. Program in Translational Medicine Rong Hsing Research Center for Translational Medicine National Chung Hsing University Taichung 40227 Taiwan. Electronic address: hlmarkc@gmail.c

BACKGROUNd:The association between human epidermal growth factor receptor-2 (HER2) amplification and brain metastasis (BM) in patients having colorectal cancer (CRC) has been suggested but not yet established. This study investigated the expression patterns of HER2, its association with BM, and its prognostic value in patients having CRC. METHOdS:We retrospectively identified 99 patients having metastatic CRC (mCRC) and BM (the BM cohort) and compared them with a cohort of 249 patients having mCRC and without BM (the stage IV cohort) by propensity score matching. Immunohistochemical studies of HER2 on all available paraffin-embedded tumour samples, either from the primary tumour, the metastasis (brain and/or extracranial sites) or both, were performed and analysed. HER2 fluorescent in situ hybridisation was applied when necessary. The expression of HER2 was compared and correlated with survival. RESULTS:HER2 amplifications were detected in 16 (18.4%) of 87 and 9 (3.6%) of 249 patients who had specimens available in the BM and stage IV cohorts, respectively (P < .001). After propensity score matching, HER2 amplification was significantly associated with BM (odds ratio: 5.38, P = .003). HER2 heterogeneity was frequently observed not only at the single tumour level but also in paired tumour samples. A marginally significant longer survival since BM was found in patients having HER2-amplified mCRC than in those without (P = .07). CONCLUSIONS:HER2 amplification was significantly associated with BM in patients having mCRC and might have prognostic value for survival since BM. Given the heterogeneity of HER2 expression, the testing of HER2 status on available tissues from both primary and metastatic tumours should be encouraged.

关键词： Brain metastasis Colorectal cancer HER2 amplification Heterogeneity Propensity score matching

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Improving the Concentration of Students With Attention deficit Hyperactivity disorder and Autism Spectrum disorder: Electroencephalographic Analysis on the Effect of Learning Activity Interventions

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International Journal of Intelligent Technologies & Applied Statistics 2020年第1期13卷 49-63页

作者： Ming-Hseuh Tsai Sy-Ruen Huang Shao-Chin Chang Yu-Ling Lo Yun-Chieh Lu Research Center for Education Systems and Policy National Academy f or Educational Research New Taipei City Taiwan Chung Chou University of Science and Technology Changhua County Taiwan Ph.D. Program of Electrical and Communications Engineering Feng-Chia University Taichung City Taiwan Department of Early Childhood Education Asia University Taichung City Taiwan

This study examined whether the learning concentration of students with attention deficit hyperactivity disorder (AdHd) or autism spectrum disorder (ASd) can be improved through participation in one-on-one learning activities. A total of 13 students with AdHd or ASd were recruited to participate in various weekly one-on-one learning activities, in an effort to improve the concentration of students with special needs. Brainwave data were collected through electroencephalography and analyzed to explore students' concentration performance in different learning activities. To achieve the objective of this study, a multi-baseline design (ABAB), a type of single-subject design method, was employed. The experiment spanned 21 weeks, covering a fall and a spring semester: the first three weeks were defined as the 1st baseline phase, the 4th to 10th weeks as the 1st experimental phase, the 11th to 13th weeks as the 2nd baseline phase, and the 14th to 21th weeks as the 2nd experimental phase. The learning activities took place in the morning self-study period once a week, and the experiment was only suspended during two of the weeks because of school events. The purpose of the two baseline phases was to collect students' brainwave data. Students' brainwaves were measured for two minutes under two scenarios; first, while they were relaxed with eyes looking straight ahead; second, they were reading a passage. The purpose of the two experimental phases was to gradually enhance students' concentration by training them to perceive their own emotions through brainwave lamps. Initial results yielded different brainwave data for students with different types of disorders. After participating in the training on learning concentration, some students demonstrated improved concentration; however, after the 2nd experimental phase, students' concentration declined. The reason was that the activities in both experimental phases were identical, and thus, they no longer provoked students' inte

关键词： Attention def icit hyperactivity disorder (AdHd) Autism spectrum disorder (ASd) Brainwave test Concentration

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Research on E-book Security Tracking Schemes

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International Journal of Network Security 2021年第4期23卷 549-557页

作者： Lin, Cheng-Ying Wu, Chia-Chun Hwang, Min-Shiang Department of Computer Science & Information Engineering Asia University 500 Lioufeng Rd. Wufeng TaichungTaichung41354 Taiwan The Ph.D. Program in Artificial Intelligence Asia University 500 Lioufeng Rd. Wufeng TaichungTaichung41354 Taiwan Department of Industrial Engineering and Management National Quemoy University No. 1 University Rd. Jinning Township Kinmen County892 Taiwan Department of Medical Research China Medical University Hospital China Medical University Taiwan

There are many business models for e-books, such as billing by time, billing by the hour, and database authorization. Copyright authorization and pricing methods are also different. How to assist the industry in formulating appropriate authorization and pricing mechanisms under different operating models is the key to the overall development of e-book services in the future. This research will be divided into two parts. The first one will start with the E-book authorization tracking mechanism. The purpose of this research is to solve the current problem of unauthorized and illegal distribution of e-books. The content consists of three parts. The first is privacy protection technology for legitimate users. Even sellers cannot obtain the personal information of legitimate users. The second part is the tracking mechanism for illegally authorized users. When the user performs illegal authorization, the e-book provider can use the tracking mechanism to find the illegal person. The third part is to build an e-book authorization management mechanism for different business models to achieve authorization tracking. The second topic will research the "e-book pricing tracking mechanism." The purpose is to design appropriate securities pricing mechanisms for different operating models. The project’s content is divided into three sub-topics: E-book pricing and tracking mechanism, E-book time-limited pricing management mechanism and building an E-book payment transaction server. The research will understand users’ browsing habits and compare them with industry interests. To develop a win-win pricing system, we will formulate an appropriate charging pricing system for different browsing methods and adopt the system according to the situation. © 2021

关键词： Crime

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Immobilization of poly(hexamethylene biguanide) to cellulose acetate- and cellulose-based nanofiber membranes for antibacterial and cytotoxic studies

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Biochemical engineering Journal 2024年 205卷

作者： dinh Thi My Huong Chi-Yun Wang Pin-Yi Chen Chien Wei Ooi Xue Er Crystal Thew Bing-Lan Liu Chen-Yaw Chiu Shen-Long Tsai Kuei-Hsiang Chen Yu-Kaung Chang Department Chemical Technology and Environment University of Technology and Education the University of Da Nang Da Nang City Viet Nam Department Chemical Engineering/ Graduate School of Biochemical Engineering Ming Chi University of Technology New Taipei City 243303 Taiwan Department Chemical Engineering National Taiwan University of Science and Technology Taipei City 10607 Taiwan International Ph.D. Program in Innovative Technology of Biomedical Engineering and Medical Devices Ming Chi University of Technology New Taipei City 243303 Taiwan Bone and Joint Research Centre Chang Gung Memorial Hospital Taoyuan City 333423 Taiwan Research Center for Intelligent Medical Devices Ming Chi University of Technology New Taipei City 243303 Taiwan Chemical Engineering Department School of Engineering Monash University Malaysia Jalan Lagoon Selatan Bandar Sunway Selangor 47500 Malaysia Advanced Engineering Platform School of Engineering Monash University Malaysia Jalan Lagoon Selatan 47500 Bandar Sunway Selangor Malaysia Department of Applied Chemistry Chaoyang University of Technology Taichung 413310 Taiwan Department of Chemical Engineering and Materials Science Yuan Ze University Zhongli Dist Taoyuan City 320315 Taiwan

To develop the environmental antibacterial membrane, the physical attachments of poly (hexamethylene biguanide) hydrochloride (phMB) on the cellulose acetate (CA) and regenerated cellulose (RC) electrospun nanofiber membranes were employed. The immobilization of phMB increased the antibacterial efficacy ( AE , %) of nanofiber membranes from 65.67% to approximately 86.13% for CA-phMB and from 35.09% to approximately 100% for RC-phMB. The results of the chemical and physical characteristics indicate that the degree of deacetylation of CA nanofiber, the surface charge of the nanofiber, and the density of phMB immobilized onto the nanofiber primarily affect the antibacterial efficacy. The use of mathematical models, such as the Temkin equilibrium model for phMB immobilization and the Monod-type model for the relationship between antibacterial activity and immobilization density of phMB provides a deeper understanding of the interactions and kinetics involved. The rapid achievement of ∼100% AE after only 10 min of contact with Escherichia coli ( E. coli ) is a notable finding, indicating the quick and efficient antibacterial action of RC-phMB nanofiber membranes. Furthermore, maintaining approximately 100% AE after 20 days of storage underscores the long-term stability of phMB immobilized on RC nanofiber membranes. The findings suggest that RC-phMB holds great promise as an antibacterial material for biomedical applications, food packaging industries, and filtration or treatment of water.

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Synthesis of Ni 0.5 Co 0.25 Mg 0.25 Ho 0.03 Fe 1.97 O 4 ferrite-grafted GNPs composites for rapid degradation of direct red 23 dye (dRd-23)

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Journal of Rare Earths 2024年

作者： Amna Muneer Muhammad Imran Arshad Mudasar Nazir Nasir Amin Kiran Mehmood Maria Akhtar Kashif Javaid Sadia Ata Ammara Aslam Lamia Ben Farhat Faisal Alresheedi Zohaib Hassan Nawaz Muhammad Tariq Sajjad Department of Physics Government College University Faisalabad 38000 Pakistan London Centre for Energy Engineering (LCEE) School of Engineering London South Bank University 103 Borough Road London SE1 0AA UK School of Chemistry University of the Punjab Lahore 54590 Pakistan Ph.D. School Silesian University of Technology 2a Akademicka Str. 44-100 Gliwice Poland Department of Physical Chemistry and Technology of Polymers Faculty of Chemistry Silesian University of Technology 44-100 Gliwice Strzody 9 Poland Department of Chemistry College of Science King Khalid University P.O. Box 9004 61413 Abha Saudi Arabia Department of Physics College of Science Qassim University Buraidah 51452 Saudi Arabia

This study explored various properties of Ni 0.5 Co 0.25 Mg 0.25 Ho 0.03 Fe 1.97 O 4 ferrite (NCMHF) / graphene nanoplatelets (GNPs) composites, including structural, optical, electrical, dielectric and magnetic properties prepared by sol-gel auto combustion route, as well as their potential for degrading of direct red 23 dye. XRd analysis reveals the presence of single-phase structures and reduced crystallite size with GNPs incorporation from 28.06 to 20.17 nm. Raman analysis reveals the ferrite spinel structure along with the G and d bands, indicating the presence of GNPs in the composites. SEM micrographs show reduced agglomeration with the addition of GNPs. A reciprocal relationship between the lattice parameter ( a ) and bandgap energy ( ) is found. It is found that for NCMHF/1.25 wt% GNPs sample, the is 2.14 eV, while the temperature coefficient of resistance (TCR) is −6.59%/K. In particular, higher permeability and magnetic quality factor ( Q ) are obtained for NCMHF/1.25 wt%GNPs composite, i.e. Q =851 at 5.5 MHz. Furthermore, NCMHF/2.25 wt% GNPs composite shows a remarkable photodegradation efficiency of direct red 23 dye, reaching 88.10% degradation rate. The outstanding electromagnetic properties and photodegradation performance of NCMHF-GNPs composites can be effectively employed in high frequency applications, microwave shielding, high-density data storage, magnetic and bolometric devices as well as cost-effective, sustainable water purification.

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Co-MOF-67/carbon black composite: A novel electrochemical platform for furazolidone detection for food analysis

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Food Chemistry 2025年 489卷 145023页

作者： Selvam, Arunkumar Gopika, Meenakumari Gopakumar Kuo, Chih-Yu Saraswathyamma, Beena Yusuf, Kareem Govindasamy, Mani National Taipei University of Technology Taipei10608 Taiwan Department of Chemical Engineering and Biotechnology National Taipei University of Technology Taipei10608 Taiwan Department of Chemistry Amrita Vishwa Vidyapeetham Amritapuri campus Clappana P O Kerala Kollam690525 India High-Value Biomaterials Research and Commercialization Center National Taipei University of Technology Taipei106 Taiwan Department of Chemistry College of Science King Saud University Riyadh11451 Saudi Arabia International Ph.D. Program in Innovative Technology of Biomedical Engineering and Medical Devices Ming Chi University of Technology New Taipei City243303 Taiwan Research Center for Intelligent Medical Devices Ming Chi University of Technology New Taipei City243303 Taiwan Department of Chemistry Korea University Seoul Seongbuk-gu Korea Republic of

Furazolidone (FZd), a nitrofuran antibiotic used for the treatment of bacterial and protozoal illnesses, generates apprehensions about its potential toxicity and mutagenicity. The swift and dependable identification of FZd in food and biological specimens is essential for public health and regulatory adherence. This study presents a novel electrochemical sensor using a glassy carbon electrode (GCE) modified with a cobalt-based metal-organic framework (Co-MOF) and carbon black (CB) composite (Co-MOF@CB/GCE) for the sensitive detection of FZd. The Co-MOF@CB composite enhances electron transport and expands the electroactive surface area. Characterization investigations confirmed the successful fabrication of the Co-MOF@CB/GCE sensor. Electrochemical analyses revealed an extensive detection range (0.4–610 μmolL−1) and a minimal detection limit (0.0875 μmolL−1). The sensor exhibited great repeatability, stability, and selectivity, demonstrating efficient FZd detection in milk, honey, and chicken. This sensor provides a reliable, economical tool for FZd detection in regulatory and public health contexts. © 2025 Elsevier Ltd

关键词： diseases

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Novel design of NiS 2 and V 3 Ni(SO 4 ) 4 · 24H 2 O composites with controllable synthetic temperature and duration as an efficient active material for battery supercapacitor hybrids

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Journal of Energy Storage 2025年 130卷

作者： Tsung-Rong Kuo Wei-Lun Huang Chutima Kongvarhodom Muhammad Saukani Sibidou Yougbaré Hung-Ming Chen Lu-Yin Lin Graduate Institute of Nanomedicine and Medical Engineering College of Biomedical Engineering Taipei Medical University Taipei 11031 Taiwan International Ph.D. Program in Biomedical Engineering College of Biomedical Engineering Taipei Medical University Taipei 11031 Taiwan Precision Medicine and Translational Cancer Research Center Taipei Medical University Hospital Taipei 11031 Taiwan Department of Chemical Engineering and Biotechnology National Taipei University of Technology Taipei Taiwan Department of Chemical Engineering King Mongkut's University of Technology Thonburi 126 Pracha-u-thit Toong-kru Bangkok 10140 Thailand Department of Mechanical Engineering Faculty of Engineering Universitas Islam Kalimantan MAB Jl. Adhyaksa No. 2 Banjarmasin 70124 Indonesia Institut de Recherche en Sciences de la Santé (IRSS-DRCO)/Nanoro 03 B.P 7192 Ouagadougou 03 Burkina Faso Gingen technology Co. LTD. Rm. 7 10F. No.189 Sec. 2 Keelung Rd. Xinyi Dist. Taipei 11054 Taiwan

Nickel–vanadium (Ni V) composites are considered as promising active materials for battery supercapacitor hybrids (BSHs), owing to multiple oxidation states, high theoretical capacitance, and tunable redox activity. Structural optimization and sulfur incorporation are effective strategies to improve conductivity and structural stability. Hydrothermal parameters such as temperature and duration significantly influence the material and electrochemical properties. In this study, novel Ni V composites are synthesized via a hydrothermal process at different temperatures and durations as the active material of BSHs. The Ni V composites primarily consist of NiS 2 and V 3 Ni(SO 4 ) 4 · 24H 2 O. The Ni V composites synthesized using 150 °C and 10 h (Ni-V150@10) shows the largest specific capacitance (C F ) of 1381.3 F/g (621.6 C/g) at 20 mV/s, owing to its favorable twisted layered structure and abundant electroactive NiS 2 . A BSH constructed with Ni-V150@10 and reduced graphene oxide electrodes shows a maximum energy density of 9.6 Wh/kg at the power density of 857 W/kg. The capacitance retention of 96.6% and a Coulombic efficiency of 96.9% are also attained after 10,000 charge/discharge cycles. This study provides a clear approach for designing high-performance active materials with controllable hydrothermal temperature and duration, which can be extended to improve the electrochemical performance of other bimetallic composites in the future.

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Unifying femtosecond and picosecond single-pulse magnetic switching in Gd-Fe-Co

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physical Review B 2021年第10期103卷 104422-104422页

作者： F. Jakobs T. A. Ostler C.-H. Lambert Y. Yang S. Salahuddin R. B. Wilson J. Gorchon J. Bokor U. Atxitia Dahlem Center for Complex Quantum Systems and Fachbereich Physik Freie Universität Berlin 14195 Berlin Germany Département de Physique Universitè de Liége (B5) B-4000 Liége Belgium College of Business Technology and Engineering Sheffield Hallam University Howard Street Sheffield S1 1WB United Kingdom Department of Electrical Engineering and Computer Sciences University of California Berkeley California 94720 USA Department of Materials Science and Engineering University of California Berkeley California 94720 USA Lawrence Berkeley National Laboratory 1 Cyclotron Road Berkeley California 94720 USA Department of Mechanical Engineering and Materials Science and Engineering Program University of California Riverside California 92521 USA

Many questions are still open regarding the physical mechanisms behind the magnetic switching in Gd-Fe-Co alloys by single optical pulses. phenomenological models suggest a femtosecond scale exchange relaxation between sublattice magnetization as the driving mechanism for switching. The recent observation of thermally induced switching in Gd-Fe-Co by using both several picosecond optical laser pulse as well as electric current pulses has questioned this previous understanding. This has raised the question of whether or not the same switching mechanics are acting at the femtosecond and picosecond scales. In this work, we aim at filling this gap in the understanding of the switching mechanisms behind thermal single-pulse switching. To that end, we have studied experimentally thermal single-pulse switching in Gd-Fe-Co alloys, for a wide range of system parameters, such as composition, laser power, and pulse duration. We provide a quantitative description of the switching dynamics using atomistic spin dynamics methods with excellent agreement between the model and our experiments across a wide range of parameters and timescales, ranging from femtoseconds to picoseconds. Furthermore, we find distinct element-specific damping parameters as a key ingredient for switching with long picosecond pulses and argue that switching with pulse durations as long as 15 ps is possible due to a low damping constant of Gd. Our findings can be easily extended to speed up dynamics in other contexts where ferrimagnetic Gd-Fe-Co alloys have been already demonstrated to show fast and energy-efficient processes, e.g., domain-wall motion in a track and spin-orbit torque switching in spintronics devices.

关键词： demagnetization Magnetic interactions Magnetic order Magnetism Spin dynamics Ultrafast magnetic effects

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CNSC-37. ROLE OF PGE2-REGULATEd NEUROINFLAMMATION IN CONSTRUCTING NEURON-NK-GLIOMA CIRCUIT FOR GLIOBLASTOMA

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Neuro-Oncology 2024年第SUPPLEMENT_8期26卷 viii49–viii49页

作者： Chen, Hsien-Chung Chang, Wen-Chang Hsu, Tsung-Yi Department of Neurosurgery Shuang Ho Hospital Taipei Medical University Taipei Taiwan Ph.D. Program in Medical Neuroscience College of Medical Science and Technology Taipei Medical University and National Health Research Institutes Taipei Taiwan TMU Research Center of Neuroscience Taipei Medical University Taipei Taiwan Graduate Institute of Medical Sciences College of Medicine Taipei Medical University Taipei Taiwan TMU Research Center for Drug Discovery Taipei Medical University Taipei Taiwan

Glioblastoma (GBM), known for its aggressive nature and poor prognosis, frequently recurs and resists standard treatments such as temozolomide (TMZ). This resistance is partly due to complex interactions within the tumor microenvironment, particularly involving neuronal excitation. Recent insights suggest that neuronal activity, through mechanisms like neurogliomal synapses, not only promotes glioma cell proliferation but also contributes to the chemoresistance observed in recurrent tumors. Our focus is on Prostaglandin E2 (PGE2), a mediator that regulates neuronal excitation, and its role in the recurrence and resistance of GBM. We discovered that PGE2 upregulates synaptic proteins and alters neurotransmitter profiles, enhancing tumor cell survival and resistance to TMZ. Specifically, increased levels of neurotransmitters such as glutamine and asparagine were observed in PGE2-rich environments, correlating with heightened chemoresistance and tumor recurrence. Co-culture experiments further demonstrated that PGE2-treated neuronal cells could induce resistance in adjacent GBM cells. These findings highlight the potential of targeting PGE2 pathways as a therapeutic strategy. A significant advancement in our study was the development and application of compound #038, a novel celecoxib derivative designed to cross the blood-brain barrier (BBB). This compound demonstrated enhanced efficacy in inhibiting GBM growth and improving survival rates in mouse models, indicating its potential as an effective therapeutic agent against GBM.

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