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  1. Article ; Online: Exploring new frontiers: cell surface vimentin as an emerging marker for circulating tumor cells and a promising therapeutic target in advanced gastric Cancer.

    Li, Heming / Zhu, Yang-Zhuangzhuang / Xu, Lu / Han, Tao / Luan, Jiasi / Li, Xin / Liu, Yuting / Wang, Zhi / Liu, Qiuge / Kong, Xiangyu / Zou, Chunpu / Su, Lin / Hou, Yifei / Chen, Xiao / Chen, Lujun / Wang, Ruoyu / Xu, Zihang / Zhao, Mingfang

    Journal of experimental & clinical cancer research : CR

    2024  Volume 43, Issue 1, Page(s) 129

    Abstract: Background: Circulating tumor cells (CTCs) hold immense promise in guiding treatment strategies for advanced gastric cancer (GC). However, their clinical impact has been limited due to challenges in identifying epithelial-mesenchymal transition (EMT)- ... ...

    Abstract Background: Circulating tumor cells (CTCs) hold immense promise in guiding treatment strategies for advanced gastric cancer (GC). However, their clinical impact has been limited due to challenges in identifying epithelial-mesenchymal transition (EMT)-CTCs using conventional methods.
    Methods: To bridge this knowledge gap, we established a detection platform for CTCs based on the distinctive biomarker cell surface vimentin (CSV). A prospective study involving 127 GC patients was conducted, comparing CTCs enumeration using both EpCAM and CSV. This approach enabled the detection of both regular and EMT-CTCs, providing a comprehensive analysis. Spiking assays and WES were employed to verify the reliability of this marker and technique. To explore the potential inducer of CSV
    Results: Our findings revealed the potential of CSV in predicting therapeutic responses and long-term prognosis for advanced GC patients. Additionally, compared to the conventional EpCAM-based CTCs detection method, the CSV-specific positive selection CTCs assay was significantly better for evaluating the therapeutic response and prognosis in advanced GC patients and successfully predicted disease progression 14.25 months earlier than radiology evaluation. Apart from its excellent role as a detection marker, CSV emerges as a promising therapeutic target for attenuating GC metastasis. It was found that fat mass and obesity associated protein (FTO) could act as a potential catalyst for CSV
    Conclusion: In summary, leveraging CSV as a universal CTCs marker represents a significant breakthrough in advancing personalized medicine for patients with advanced GC. This research not only paves the way for tailored therapeutic strategies but also underscores the pivotal role of CSV in enhancing GC management, opening new frontiers for precision medicine.
    MeSH term(s) Animals ; Female ; Humans ; Male ; Mice ; Middle Aged ; Biomarkers, Tumor/metabolism ; Cell Line, Tumor ; Epithelial-Mesenchymal Transition ; Neoplastic Cells, Circulating/metabolism ; Neoplastic Cells, Circulating/pathology ; Prospective Studies ; Stomach Neoplasms/pathology ; Stomach Neoplasms/metabolism ; Stomach Neoplasms/genetics ; Vimentin/metabolism
    Chemical Substances Biomarkers, Tumor ; Vimentin ; VIM protein, human
    Language English
    Publishing date 2024-04-30
    Publishing country England
    Document type Journal Article
    ZDB-ID 803138-1
    ISSN 1756-9966 ; 0392-9078
    ISSN (online) 1756-9966
    ISSN 0392-9078
    DOI 10.1186/s13046-024-03043-6
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: The Tian-Men-Dong decoction suppresses the tumour-infiltrating G-MDSCs via IL-1β-mediated signalling in lung cancer.

    Su, Lin / Zhang, Fei / Liu, Ming-Xi / Li, Hong / Li, Qiang / Zhu, Yang-Zhuangzhuang / Hou, Yi-Fei / Chen, Xiao / Wang, Xiao-Yu / Qian, Chun-Mei / Yao, Chao / Wang, Li-Xin / Jiao, Xiao-Ning / Zhu, Xian-Dan / Xu, Zi-Hang / Zou, Chun-Pu

    Journal of ethnopharmacology

    2023  Volume 313, Page(s) 116491

    Abstract: Ethnopharmacological relevance: The traditional Chinese medicine (TCM) Tian-Men-Dong decoction (TD) has been able to effectively treat lung cancer in China for thousands of years. TD improves the quality of life in lung cancer patients by promoting ... ...

    Abstract Ethnopharmacological relevance: The traditional Chinese medicine (TCM) Tian-Men-Dong decoction (TD) has been able to effectively treat lung cancer in China for thousands of years. TD improves the quality of life in lung cancer patients by promoting nourishment of yin and reducing dryness, clearing the lung and removing toxins. Pharmacological studies show that TD contains active antitumour ingredients, but its underlying mechanism remains unknown.
    Aim of the study: This study aims at exploring potential mechanisms of TD in the treatment of lung cancer by regulating granulocytic-myeloid-derived suppressor cells (G-MDSCs).
    Materials and methods: An orthotopic lung cancer mouse model was generated by intrapulmonary injection with LLC-luciferase cells in immunocompetent C57BL/6 mice or immunodeficient nude mice. TD/saline was orally administered once to the model mice daily for 4 weeks. Live imaging was conducted to monitor tumour growth. Immune profiles were detected by flow cytometry. H&E and ELISA were applied to test the cytotoxicity of the TD treatment. RT-qPCR and western blotting were performed to detect apoptosis-related proteins in G-MDSCs. A neutralizing antibody (anti-Ly6G) was utilized to exhaust the G-MDSCs via intraperitoneal injection. G-MDSCs were adoptively transferred from wild-type tumour-bearing mice. Immunofluorescence, TUNEL and Annexin V/PI staining were conducted to analyse apoptosis-related markers. A coculture assay of purified MDSCs and T cells labelled with CFSE was performed to test the immunosuppressive activity of MDSCs. The presence of TD/IL-1β/TD + IL-1β in purified G-MDSCs cocultured with the LLC system was used for ex vivo experiments to detect IL-1β-mediated apoptosis of G-MDSCs.
    Results: TD prolonged the survival of immune competent C57BL/6 mice in an orthotopic lung cancer model, but did not have the same effect in immunodeficient nude mice, indicating that its antitumour properties of TD are exerted by regulating immunity. TD induced G-MDSC apoptosis via the IL-1β-mediated NF-κB signalling cascade leading to effectively weaken the immunosuppressive activity of G-MDSCs and promote CD8
    Conclusion: This study reveals for the first time that TD, a classic TCM prescription, is able to regulate G-MDSC activity and trigger its apoptosis via the IL-1β-mediated NF-κB signalling pathway, reshaping the tumour microenvironment and demonstrating antitumour effects. These findings provide a scientific foundation the clinical treatment of lung cancer with TD.
    MeSH term(s) Mice ; Animals ; Myeloid-Derived Suppressor Cells ; Mice, Nude ; NF-kappa B/metabolism ; Quality of Life ; Mice, Inbred C57BL ; Lung Neoplasms/metabolism ; Immunosuppressive Agents/pharmacology ; Tumor Microenvironment
    Chemical Substances NF-kappa B ; Immunosuppressive Agents
    Language English
    Publishing date 2023-04-16
    Publishing country Ireland
    Document type Journal Article
    ZDB-ID 134511-4
    ISSN 1872-7573 ; 0378-8741
    ISSN (online) 1872-7573
    ISSN 0378-8741
    DOI 10.1016/j.jep.2023.116491
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: The Tian-Men-Dong decoction suppresses the tumour-infiltrating G-MDSCs via IL-1β-mediated signalling in lung cancer

    Su, Lin / Zhang, Fei / Liu, Ming-xi / Li, Hong / Li, Qiang / Zhu, Yang-zhuangzhuang / Hou, Yi-fei / Chen, Xiao / Wang, Xiao-yu / Qian, Chun-mei / Yao, Chao / Wang, Li-xin / Jiao, Xiao-ning / Zhu, Xian-dan / Xu, Zi-hang / Zou, Chun-pu

    Journal of Ethnopharmacology. 2023 Apr. 16, p.116491-

    2023  , Page(s) 116491–

    Abstract: The traditional Chinese medicine (TCM) Tian-Men-Dong decoction (TD) has been able to effectively treat lung cancer in China for thousands of years. TD improves the quality of life in lung cancer patients by promoting nourishment of yin and reducing ... ...

    Abstract The traditional Chinese medicine (TCM) Tian-Men-Dong decoction (TD) has been able to effectively treat lung cancer in China for thousands of years. TD improves the quality of life in lung cancer patients by promoting nourishment of yin and reducing dryness, clearing the lung and removing toxins. Pharmacological studies show that TD contains active antitumour ingredients, but its underlying mechanism remains unknown. This study aims at exploring potential mechanisms of TD in the treatment of lung cancer by regulating granulocytic-myeloid-derived suppressor cells (G-MDSCs). An orthotopic lung cancer mouse model was generated by intrapulmonary injection with LLC-luciferase cells in immunocompetent C57BL/6 mice or immunodeficient nude mice. TD/saline was orally administered once to the model mice daily for 4 weeks. Live imaging was conducted to monitor tumour growth. Immune profiles were detected by flow cytometry. H&E and ELISA were applied to test the cytotoxicity of the TD treatment. RT–qPCR and western blotting were performed to detect apoptosis-related proteins in G-MDSCs. A neutralizing antibody (anti-Ly6G) was utilized to exhaust the G-MDSCs via intraperitoneal injection. G-MDSCs were adoptively transferred from wild-type tumour-bearing mice. Immunofluorescence, TUNEL and Annexin V/PI staining were conducted to analyse apoptosis-related markers. A coculture assay of purified MDSCs and T cells labelled with CFSE was performed to test the immunosuppressive activity of MDSCs. The presence of TD/IL-1β/TD + IL-1β in purified G-MDSCs cocultured with the LLC system was used for ex vivo experiments to detect IL-1β-mediated apoptosis of G-MDSCs. TD prolonged the survival of immune competent C57BL/6 mice in an orthotopic lung cancer model, but did not have the same effect in immunodeficient nude mice, indicating that its antitumour properties of TD are exerted by regulating immunity. TD induced G-MDSC apoptosis via the IL-1β-mediated NF-κB signalling cascade leading to effectively weaken the immunosuppressive activity of G-MDSCs and promote CD8⁺ T-cell infiltration, which was supported by both the depletion and adoptive transfer of G-MDSCs assays. In addition, TD also showed minimal cytotoxicity both in vivo and in vitro. This study reveals for the first time that TD, a classic TCM prescription, is able to regulate G-MDSC activity and trigger its apoptosis via the IL-1β-mediated NF-κB signalling pathway, reshaping the tumour microenvironment and demonstrating antitumour effects. These findings provide a scientific foundation the clinical treatment of lung cancer with TD.
    Keywords Oriental traditional medicine ; T-lymphocytes ; antibodies ; apoptosis ; coculture ; cytotoxicity ; flow cytometry ; fluorescent antibody technique ; immunosuppression ; intraperitoneal injection ; lung neoplasms ; lungs ; mice ; models ; quality of life ; China ; Traditional Chinese medicine ; Tian-Men-Dong decoction ; G-MDSCs ; CD8+ T cells ; IL-1β
    Language English
    Dates of publication 2023-0416
    Publishing place Elsevier B.V.
    Document type Article ; Online
    Note Pre-press version
    ZDB-ID 134511-4
    ISSN 1872-7573 ; 0378-8741
    ISSN (online) 1872-7573
    ISSN 0378-8741
    DOI 10.1016/j.jep.2023.116491
    Database NAL-Catalogue (AGRICOLA)

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  4. Article ; Online: Ze-Qi-Tang Formula Induces Granulocytic Myeloid-Derived Suppressor Cell Apoptosis via STAT3/S100A9/Bcl-2/Caspase-3 Signaling to Prolong the Survival of Mice with Orthotopic Lung Cancer.

    Xu, Zi-Hang / Zhu, Yang-Zhuangzhuang / Su, Lin / Tang, Xue-Yang / Yao, Chao / Jiao, Xiao-Ning / Hou, Yi-Fei / Chen, Xiao / Wei, Lu-Yao / Wang, Wan-Tao / Wang, Jie / Gong, Chen-Yuan / Zhu, Xian-Dan / Zhang, Fei / Zhu, Shi-Guo / Zou, Chun-Pu

    Mediators of inflammation

    2021  Volume 2021, Page(s) 8856326

    Abstract: Non-small-cell lung cancer (NSCLC) remains the most common malignancy with the highest morbidity and mortality worldwide. In our previous study, we found that a classic traditional Chinese medicine (TCM) formula Ze-Qi-Tang (ZQT), which has been used in ... ...

    Abstract Non-small-cell lung cancer (NSCLC) remains the most common malignancy with the highest morbidity and mortality worldwide. In our previous study, we found that a classic traditional Chinese medicine (TCM) formula Ze-Qi-Tang (ZQT), which has been used in the treatment of respiratory diseases for thousands of years, could directly inhibit the growth of human NSCLC cells via the p53 signaling pathway. In this study, we explored the immunomodulatory functions of ZQT. We found that ZQT significantly prolonged the survival of orthotopic lung cancer model mice by modulating the tumor microenvironment (TME). ZQT remarkably reduced the number of MDSCs (especially G-MDSCs) and inhibited their immunosuppressive activity by inducing apoptosis in these cells via the STAT3/S100A9/Bcl-2/caspase-3 signaling pathway. When G-MDSCs were depleted, the survival promotion effect of ZQT and its inhibitory effect on lung luminescence signal disappeared in tumor-bearing mice. This is the first study to illustrate the immunomodulatory effect of ZQT in NSCLC and the underlying molecular mechanism.
    MeSH term(s) Animals ; Apoptosis/drug effects ; Calgranulin B/physiology ; Carcinoma, Non-Small-Cell Lung/drug therapy ; Carcinoma, Non-Small-Cell Lung/mortality ; Carcinoma, Non-Small-Cell Lung/pathology ; Caspase 3/physiology ; Cell Line, Tumor ; Drugs, Chinese Herbal/pharmacology ; Drugs, Chinese Herbal/therapeutic use ; Granulocytes/drug effects ; Granulocytes/pathology ; Lung Neoplasms/drug therapy ; Lung Neoplasms/mortality ; Lung Neoplasms/pathology ; Medicine, Chinese Traditional ; Mice ; Mice, Inbred C57BL ; Myeloid-Derived Suppressor Cells/drug effects ; Myeloid-Derived Suppressor Cells/pathology ; Proto-Oncogene Proteins c-bcl-2/physiology ; STAT3 Transcription Factor/physiology ; Signal Transduction/drug effects ; Tumor Microenvironment
    Chemical Substances Calgranulin B ; Drugs, Chinese Herbal ; Proto-Oncogene Proteins c-bcl-2 ; S100A9 protein, mouse ; STAT3 Transcription Factor ; Stat3 protein, mouse ; Caspase 3 (EC 3.4.22.-)
    Language English
    Publishing date 2021-04-01
    Publishing country United States
    Document type Journal Article
    ZDB-ID 1137605-3
    ISSN 1466-1861 ; 0962-9351
    ISSN (online) 1466-1861
    ISSN 0962-9351
    DOI 10.1155/2021/8856326
    Database MEDical Literature Analysis and Retrieval System OnLINE

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