| 1 | Investigating the Immunogenic Cell Death‑Dependent Subtypes and Prognostic Signature of Triple‑Negative Breast Cancer显示文摘Recently,immunotherapy has emerged as a promising and efective method for treating triple-negative breast cancer(TNBC).However,challenges still persist.Immunogenic cell death(ICD)is considered a prospective treatment and potential combinational treatment strategy as it induces an anti-tumor immune response by presenting the antigenic epitopes of dead cells.Nevertheless,the ICD process in TNBC and its impact on disease progression and the response to immunotherapy are not well understood.In this study,we observed dysregulation of the ICD process and verifed the altered expression of prognostic ICD genes in TNBC through quantitative real-time polymerase chain reaction(qRT-PCR)analysis.To investigate the potential role of the ICD process in TNBC progression,we determined the ICD-dependent subtypes,and two were identifed.Analysis of their distinct tumor immune microenvironment(TIME)and cancer hallmark features revealed that Cluster 1 and 2 corresponded to the immune“cold”and“hot”phenotypes,respectively.In addition,we constructed the prognostic signature ICD score of TNBC patients and demonstrated its clinical independence and generalizability.The ICD score could also serve as a potential biomarker for immune checkpoint blockade and may aid in the identifcation of targeted efective agents for individualized clinical strategies. | Youyang Shi Yuanyuan Wu Feifei Li Kexin Jiang Xiaofang Fang Yu Wang Xiaoyun Song Rui Wang Lixin Chen Jinzhou Zheng Chunyu Wu Yuenong Qin Xiaofei Liu Sheng Liu | 2024 | Phenomics2024,4,1: | 0 |
| 2 | Xianling Lianxia formula enhances the inhibitory effects of trastuzumab on HER2-positive breast cancer显示文摘Human epidermal growth factor receptor 2(HER2)-positive breast cancer(BC)is characterized by high invasiveness.Trastuzumab considerably improves the prognoses of HER2-positive BC,but some patients exhibit drug resistance.In this study,the effects of XLLXF combined with trastuzumab on the proliferation,apoptosis,invasion,and migration of HER2-positive BC cells are evaluated,and network pharmacology is performed.Then,we conduct an in vivo study using a xenograft mouse model of HER2-positive BC,and tumor growth is monitored.The expression levels of cytokines are measured by ELISA.Molecular docking is performed to observe the binding stability of IL2,JAK,STAT,and TNF with curcumenol,icariside-II,lobetyolin,and scutellarein.Finally,we observe changes in JAK1 and TNF-αin tumor tissues by immunohistochemistry.The results show that XLLXF enhances the inhibitory effects of trastuzumab on the proliferation,colony formation ability,migration,and invasion of HER2-positive BC cells and promotes apoptosis.Network pharmacology reveals that XLLXF may exert its effects on HER2-positive BC by modulating pathways such as the ErbB,JAK-STAT,and NF-κB pathways.Potential targets include cytokines closely related to immune function.In the in vivo study,XLLXF synergistically enhances the inhibitory effects of trastuzumab on tumor growth.ELISA reveals that XLLXF combined with trastuzumab increases the levels of IL-15,IL-2,TNF-α,and IFN-γin tumor-bearing mice.Immunohistochemistry confirms that XLLXF can regulate the expressions of JAK1 and TNF-α.This study demonstrates that XLLXF can synergistically enhance the efficacy of trastuzumab in targeting HER2-positive BC.The mechanism may involve the modulation of inflammatory factors. | Feifei Li Yuanyuan Wu Youyang Shi Xiaofei Liu Ying Xie Sheng Liu | 2024 | Acta Biochimica et Biophysica Sinica2024,56,3: | 0 |