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Validation of hyperthermia as an enhancer of chemotherapeutic efficacy: insights from a bladder cancer organoid model

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单位: [1]Institute of Reproductive Health, Tongji Medical College, Huazhong University of Science and Technology, Hubei, China [2]Department of Urology, the First Affiliated Hospital, School of Medicine, Zhejiang University, Zhejiang, China [3]College of Pharmacy, Hubei University of Science and Technology, Hubei, China [4]Department of Cardiovascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Hubei, China [5]Wuhan Britain-China School, Hubei, China [6]Bio-X, Stanford University School of Medicine, Stanford, CA, USA [7]Department of Urology, Jianyang First Hospital, Fujian, China [8]Department of Urology,Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology,Hubei,China [9]Suzhou OptoMedic Technologies Inc, Jiangsu, China [10]School of Life Science and Technology, Wuhan Polytechnic University, Hubei, China
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关键词: Hyperthermia chemotherapy NMIBC RT 4 organoids bladder cancer

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This study aimed to evaluate the combined efficacy of hyperthermia and chemotherapy using a bladder cancer organoid model and to explore hyperthermia-related molecular pathways.Tumor organoids were generated by embedding RT4 bladder cancer cells into Matrigel. The resulting organoids were treated with pirarubicin or gemcitabine at 37 °C or 42 °C. Proliferation was determined by Ki67 immunofluorescence staining, and apoptosis was assessed using a TdT-mediated dUTP nick end labeling (TUNEL) assay. RNA sequencing was used to identify the differentially expressed genes.Bladder cancer organoids were successfully established and exhibited robust proliferative abilities. Treatment with gemcitabine or pirarubicin under hyperthermic conditions caused pronounced structural damage to the organoids and increased cell death compared to that in the normothermically treated group. Furthermore, Ki67 labeling and TUNEL assays showed that the hyperthermia chemotherapy group showed a significantly reduced proliferation rate and high level of apoptosis. Finally, RNA sequencing revealed the IFN-γ signaling pathway to be associated with hyperthermia.Overall, hyperthermia combined with chemotherapy exerted better therapeutic effects than those of normothermic chemotherapy in grade 1-2 non-muscle-invasive bladder cancer, potentially through activation of the IFN-γ-JAK-STAT pathway.

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出版当年[2023]版:
大类 | 3 区 医学
小类 | 3 区 肿瘤学 3 区 核医学
最新[2025]版:
大类 | 3 区 医学
小类 | 3 区 肿瘤学 3 区 核医学
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出版当年[2022]版:
Q2 RADIOLOGY, NUCLEAR MEDICINE & MEDICAL IMAGING Q3 ONCOLOGY
最新[2023]版:
Q2 ONCOLOGY Q2 RADIOLOGY, NUCLEAR MEDICINE & MEDICAL IMAGING

影响因子: 最新[2023版] 最新五年平均 出版当年[2022版] 出版当年五年平均 出版前一年[2021版] 出版后一年[2023版]

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第一作者单位: [1]Institute of Reproductive Health, Tongji Medical College, Huazhong University of Science and Technology, Hubei, China
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通讯机构: [1]Institute of Reproductive Health, Tongji Medical College, Huazhong University of Science and Technology, Hubei, China [*1]Institute of Reproductive Health, Tongji Medical College, Huazhong University of Science and Technology, Hubei, China.
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