Clinical and Experimental Medicine最新文献_第2页

Comprehensive review of drug-mediated ICD inhibition of breast cancer: mechanism, status, and prospects. 药物介导的 ICD 抑制乳腺癌综合综述：机制、现状和前景。

IF 3.2 4区医学

Clinical and Experimental Medicine Pub Date : 2024-09-26 DOI: 10.1007/s10238-024-01482-1

Yang Wang, Rui Yang, Ying Xie, Xi-Qiu Zhou, Jian-Feng Yang, You-Yang Shi, Sheng Liu

{"title":"Comprehensive review of drug-mediated ICD inhibition of breast cancer: mechanism, status, and prospects.","authors":"Yang Wang, Rui Yang, Ying Xie, Xi-Qiu Zhou, Jian-Feng Yang, You-Yang Shi, Sheng Liu","doi":"10.1007/s10238-024-01482-1","DOIUrl":"https://doi.org/10.1007/s10238-024-01482-1","url":null,"abstract":"The escalating incidence of breast cancer (BC) in women underscores its grave health threat. Current molecular insights into BC's post-adjuvant therapy cure remain elusive, necessitating active treatment explorations. Immunotherapy, notably chemotherapy-induced immunogenic cell death (ICD), has emerged as a promising BC therapy. ICD harnesses chemotherapeutics to activate anti-tumor immunity via DAMPs, fostering long-term T-cell memory and primary BC cure. Besides chemotherapy drugs, Nanodrugs, traditional Chinese medicine (TCM) and ICIs also induce ICD, boosting immune response. ICIs, like PD-1/PD-L1 inhibitors, revolutionize cancer treatment but face limited success in cold tumors. Thus, ICD induction combined with ICIs is studied extensively for BC immunotherapy. This article reviews the mechanism of ICD related drugs in BC and provides reference for the research and development of BC treatment, in order to explore more effective clinical treatment of BC, we hope to explore more ICD inducers and make ICIs more effective vaccines.","PeriodicalId":10337,"journal":{"name":"Clinical and Experimental Medicine","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11427550/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142342778","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The NLRP3 inflammasome in allergic diseases: mechanisms and therapeutic implications. 过敏性疾病中的 NLRP3 炎症小体：机制和治疗意义。

IF 3.2 4区医学

Clinical and Experimental Medicine Pub Date : 2024-09-26 DOI: 10.1007/s10238-024-01492-z

Huiqin Zhou, Li Wang, Wei Lv, Hongmeng Yu

{"title":"The NLRP3 inflammasome in allergic diseases: mechanisms and therapeutic implications.","authors":"Huiqin Zhou, Li Wang, Wei Lv, Hongmeng Yu","doi":"10.1007/s10238-024-01492-z","DOIUrl":"10.1007/s10238-024-01492-z","url":null,"abstract":"In recent years, there has been a global increase in the prevalence of allergic diseases, including allergic rhinitis, chronic rhinosinusitis, allergic asthma, atopic dermatitis, allergic conjunctivitis, and food allergies. Since the pathogenic mechanisms of these allergic diseases are not yet fully understood, targeted and effective therapies are lacking. The NLRP3 inflammasome, a multiprotein complex implicated in various inflammatory diseases, can be activated by diverse stimuli. It assembles into NLRP3 inflammasome complexes through conformational changes, initiating the proteolytic cleavage of dormant procaspase-1 into active caspase-1 and promoting the maturation of inflammatory cytokines, including IL-1β and IL-18. Dysfunction of the NLRP3 inflammasome may serve as a key driver of inflammatory diseases, leading to pyroptosis and amplifying the local inflammatory response. As preliminarily demonstrated, specific NLRP3 inflammatory vesicle inhibitors play refectory roles in animal models of allergic diseases, and it is believed that specific NLRP3 inflammasome inhibitors may be potential therapeutic agents for allergic diseases. This review highlights the progress of research on the NLRP3 inflammasome in allergic diseases, explores its contribution to different types of allergic diseases, and identifies promising clinical targets for intervention.","PeriodicalId":10337,"journal":{"name":"Clinical and Experimental Medicine","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11427518/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142342784","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Evaluation of PD-1 and interleukin-10-receptor expression by T lymphocytes in malignant and benign pleural effusions. 评估恶性和良性胸腔积液中 T 淋巴细胞的 PD-1 和白细胞介素-10-受体表达。

IF 3.2 4区医学

Clinical and Experimental Medicine Pub Date : 2024-09-26 DOI: 10.1007/s10238-024-01485-y

B Mosleh, B Hammer, A El-Gazzar, M Kramer, S Ayazseven, D Bernitzky, S Geleff, Marco Idzko, D Gompelmann, M A Hoda

{"title":"Evaluation of PD-1 and interleukin-10-receptor expression by T lymphocytes in malignant and benign pleural effusions.","authors":"B Mosleh, B Hammer, A El-Gazzar, M Kramer, S Ayazseven, D Bernitzky, S Geleff, Marco Idzko, D Gompelmann, M A Hoda","doi":"10.1007/s10238-024-01485-y","DOIUrl":"10.1007/s10238-024-01485-y","url":null,"abstract":"PD-1 (programmed cell death protein-1)/PD-L1 (programmed cell death ligand 1) as well as IL-10 (interleukin-10)/IL-10R (interleukin-10 receptor) interactions play a major role in tumor immune evasion in various malignancies. Several studies investigated the expression of PD-1 on T lymphocytes in pleural effusions (PE) in patients with malignant diseases. However, results in malignant pleural effusions (MPE) compared to benign PE (BPE) are underreported. In this prospective study, 51 patients (median age 66 years, IQR 54-78, 47% male) with PE of malignant or benign origin at the Medical University of Vienna between March 2021 and November 2022 were enrolled and divided into three groups according to the cytological results (group 1: MPE [n = 24, 47%]; group 2: BPE in malignant disease [n = 22, 43%]; group 3: BPE in benign disease [n = 5, 10%]). In the cytological samples, T cells were analyzed for the expression of PD-1 and IL-10R via flow cytometry. In MPE, the proportion of PD-1+ T lymphocytes on CD4+ cells was significantly lower than in BPE (40.1 vs. 56.3 in group 1 vs. 3, p = 0.019). Moreover, a significantly lower expression of PD-1+ IL-10R+ CD8+ (9.6 vs. 35.2 in group 1 vs. 2, p = 0.016; 9.6 vs. 25.0 in group 1 vs. 3, p = 0.032) and a significantly higher expression of PD-1-IL-10R-CD8+ T lymphocytes (43.7 vs. 14.0 in group1 vs. 2, p = 0.045; 43.7 vs. 23.3 in group 1 vs. 3, p = 0.032) were observed in MPE when compared to BPE. The frequency of T cells expressing PD-1 and IL-10R on CD8+ T cells is significantly lower in MPE compared to BPE regardless of the underlying disease indicating a different microenvironment in PE driven by the presence of tumor cells. Our observation spotlights the possible involvement of PD-1 and IL-10R in MPE.","PeriodicalId":10337,"journal":{"name":"Clinical and Experimental Medicine","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11427529/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142342780","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Serum markers of microbial translocation and intestinal damage in assessment of gastrointestinal tract involvement in systemic sclerosis 评估系统性硬化症胃肠道受累情况的微生物转运和肠道损伤血清标志物

IF 4.6 4区医学

Clinical and Experimental Medicine Pub Date : 2024-09-19 DOI: 10.1007/s10238-024-01466-1

Chiara Pellicano, Alessandra Oliva, Amalia Colalillo, Antonietta Gigante, Elisa D’Aliesio, Dania Al Ismail, Maria Claudia Miele, Rosario Cianci, Claudio Maria Mastroianni, Edoardo Rosato

{"title":"Serum markers of microbial translocation and intestinal damage in assessment of gastrointestinal tract involvement in systemic sclerosis","authors":"Chiara Pellicano, Alessandra Oliva, Amalia Colalillo, Antonietta Gigante, Elisa D’Aliesio, Dania Al Ismail, Maria Claudia Miele, Rosario Cianci, Claudio Maria Mastroianni, Edoardo Rosato","doi":"10.1007/s10238-024-01466-1","DOIUrl":"https://doi.org/10.1007/s10238-024-01466-1","url":null,"abstract":"Gastrointestinal (GI) tract involvement affects up to 90% of Systemic sclerosis (SSc) patients. The presence of GI symptoms is assessed by the University of California, Los Angeles, and Scleroderma Clinical Trials Consortium Gastrointestinal Scale (UCLA SCTC GIT 2.0). Microbial translocation (MT) is reported in SSc patients consequently to increased intestinal permeability due to intestinal damage (ID) and dysbiosis. Aim of this study was to assess circulating levels of LBP and EndoCab IgM (markers of MT), IL-6 (marker of inflammation), I-FABP and Zonulin (markers of ID) in a cohort of SSc patients and healthy controls (HC). Moreover, we aimed to correlate these parameters with severity of GI symptoms. UCLA SCTC GIT 2.0 questionnaire was administered to 60 consecutive SSc patients. Markers of MT, inflammation and ID were evaluated in SSc patients and HC. SSc patients had higher median value of markers of MT, inflammation and ID than HC. The logistic regression analysis showed LBP as the only variable associated with an UCLA total score “moderate-to-very severe” [OR 1.001 (CI 95%: 1.001–1.002), p < 0.001]. The logistic regression analysis showed LBP [OR 1.002 (CI 95%: 1.001–1.003), p < 0.01] and disease duration [OR 1.242 (CI 95%: 1.023–1.506), p < 0.05] as variables associated with UCLA distension/bloating “moderate-to-very severe”. The logistic regression analysis showed LBP as the only variable associated with UCLA diarrhea “moderate-to-very severe” [OR 1.002 (CI 95%: 1.001–1.003), p < 0.01]. SSc patients with dysregulation gut mucosal integrity expressed by high levels of MT and ID biomarkers had more severe GI symptoms.","PeriodicalId":10337,"journal":{"name":"Clinical and Experimental Medicine","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142250947","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Angiopoietin-4 expression and potential mechanisms in carcinogenesis: Current achievements and perspectives 血管生成素-4 的表达和致癌的潜在机制：当前成就与前景

IF 4.6 4区医学

Clinical and Experimental Medicine Pub Date : 2024-09-19 DOI: 10.1007/s10238-024-01449-2

Wenchao Zhou, Qunfeng Zhang, Junling Chen, Jinpeng Gan, Yukun Li, Juan Zou

引用次数: 0

Molecular profiling and therapeutic tailoring to address disease heterogeneity in systemic lupus erythematosus 针对系统性红斑狼疮疾病异质性的分子图谱分析和定制疗法

IF 4.6 4区医学

Clinical and Experimental Medicine Pub Date : 2024-09-19 DOI: 10.1007/s10238-024-01484-z

Abhibroto Karmakar, Uma Kumar, Smitha Prabhu, Vinod Ravindran, Shankar Prasad Nagaraju, Varashree Bolar Suryakanth, Mukhyaprana M. Prabhu, Subhradip Karmakar

{"title":"Molecular profiling and therapeutic tailoring to address disease heterogeneity in systemic lupus erythematosus","authors":"Abhibroto Karmakar, Uma Kumar, Smitha Prabhu, Vinod Ravindran, Shankar Prasad Nagaraju, Varashree Bolar Suryakanth, Mukhyaprana M. Prabhu, Subhradip Karmakar","doi":"10.1007/s10238-024-01484-z","DOIUrl":"https://doi.org/10.1007/s10238-024-01484-z","url":null,"abstract":"Systemic lupus erythematosus (SLE) is a chronic, heterogeneous, systemic autoimmune disease characterized by autoantibody production, complement activation, and immune complex deposition. SLE predominantly affects young, middle-aged, and child-bearing women with episodes of flare-up and remission, although it affects males at a much lower frequency (female: male; 7:1 to 15:1). Technological and molecular advancements have helped in patient stratification and improved patient prognosis, morbidity, and treatment regimens overall, impacting quality of life. Despite several attempts to comprehend the pathogenesis of SLE, knowledge about the precise molecular mechanisms underlying this disease is still lacking. The current treatment options for SLE are pragmatic and aim to develop composite biomarkers for daily practice, which necessitates the robust development of novel treatment strategies and drugs targeting specific responsive pathways. In this communication, we review and aim to explore emerging therapeutic modalities, including multiomics-based approaches, rational drug design, and CAR-T-cell-based immunotherapy, for the management of SLE.","PeriodicalId":10337,"journal":{"name":"Clinical and Experimental Medicine","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142250945","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Characteristic changes in the mRNA expression profile of plasma exosomes from patients with MPO-ANCA-associated vasculitis and its possible correlations with pathogenesis MPO-ANCA相关性血管炎患者血浆外泌体mRNA表达谱的特征性变化及其与发病机制的可能相关性

IF 4.6 4区医学

Clinical and Experimental Medicine Pub Date : 2024-09-17 DOI: 10.1007/s10238-024-01457-2

Yangfan Chen, Dongqing Zhou, Xin Qian, Shangqing Ge, Zongwen Shuai

{"title":"Characteristic changes in the mRNA expression profile of plasma exosomes from patients with MPO-ANCA-associated vasculitis and its possible correlations with pathogenesis","authors":"Yangfan Chen, Dongqing Zhou, Xin Qian, Shangqing Ge, Zongwen Shuai","doi":"10.1007/s10238-024-01457-2","DOIUrl":"https://doi.org/10.1007/s10238-024-01457-2","url":null,"abstract":"To explore the expression patterns and potential roles of mRNAs in exosomes from patients with myeloperoxidase-specific anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (MPO-AAV). Plasma exosomes were isolated from MPO-AAV patients and healthy controls (HCs) to screen for differential mRNA expression via exosomal mRNA sequencing. The differentially expressed mRNAs in exosomes from the 2 groups were comparatively explored by bioinformatics analysis. The six most differentially expressed mRNAs were selected and validated in larger groups of MPO-AAV patients and HCs by real-time quantitative polymerase chain reaction (RT‒qPCR). The relationships between these selected mRNAs and patient characteristics were statistically analyzed. Compared with HCs, a total of 1077 mRNAs in exosomes from MPO-AAV patients were found to be significantly upregulated, including DEPDC1B and TPST1, while NSUN4 and AK4 were significantly downregulated. Statistical analysis did not reveal any correlation between the six selected mRNAs and clinical indicators, including disease activity. GO enrichment analysis revealed that these differentially expressed genes participate in various enzyme activities, protein synthesis, etc. KEGG pathway analysis revealed that metabolic pathways, cell adhesion molecules, epithelial signaling, and mitogen-activated protein kinase (MAPK) signaling pathways were significantly enriched in the exosomal mRNAs. There were significant differences in the expression of exosomal mRNAs between MPO-AAV patients and HCs, which may be related to the occurrence and development of MPO-AAV. These findings provide clues for further investigations of MPO-AAV pathogenesis and the identification of new potential therapeutic targets.","PeriodicalId":10337,"journal":{"name":"Clinical and Experimental Medicine","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142250948","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Ultrasound shear wave elastography for assessing minor salivary gland involvement in anti-centromere antibody-positive primary Sjögren’s syndrome: a retrospective study 超声剪切波弹性成像评估抗中心粒抗体阳性原发性斯约格伦综合征患者唾液腺轻微受累情况：一项回顾性研究

IF 4.6 4区医学

Clinical and Experimental Medicine Pub Date : 2024-09-17 DOI: 10.1007/s10238-024-01486-x

Xinyu Wang, Xujie Wang, Jian Wu, Fenglin Dong, Xin Chang, Aju Wang

{"title":"Ultrasound shear wave elastography for assessing minor salivary gland involvement in anti-centromere antibody-positive primary Sjögren’s syndrome: a retrospective study","authors":"Xinyu Wang, Xujie Wang, Jian Wu, Fenglin Dong, Xin Chang, Aju Wang","doi":"10.1007/s10238-024-01486-x","DOIUrl":"https://doi.org/10.1007/s10238-024-01486-x","url":null,"abstract":"The aim of this study is to investigate salivary gland involvement in patients with anti-centromere antibody (ACA)-positive primary Sjögren’s syndrome (pSS). We retrospectively evaluated 134 patients with pSS. Patients were divided into four groups based on the results of ACA and SSA antibodies. We compared clinical manifestations, laboratory findings, salivary gland shear wave elastography, minor salivary gland biopsy results, and EULAR Sjögren’s syndrome disease activity index (ESSDAI) scores among the four groups. A total of 134 patients were classified as having pSS and divided into three groups based on serum ACA and anti-SSA antibody status: ACA + SSA + , ACA + SSA-, ACA-SSA + , and seronegative. The primary analysis focused on comparing the clinical and SWE findings between the ACA + SSA + and ACA + SSA- groups. In the double-positive group, SWE revealed fewer minor salivary glands along with higher mean (Emean) and maximum (Emax) values of Young’s moduli than those in the ACA-negative group. Patients in the positive group had increased occurrence of Raynaud’s phenomenon, liver involvement, and a higher incidence of malignancy (P < 0.05). ACA-positive pSS patients are a subgroup with different clinical manifestations and more pronounced involvement of the minor salivary glands. SWE findings revealed that ACA-positive patients exhibit significantly higher mean and maximum stiffness values compared to ACA-negative patients, indicating more extensive glandular fibrosis and involvement. These results underscore the utility of SWE as a valuable method for evaluating salivary gland pathology and supporting the stratification of pSS patients.","PeriodicalId":10337,"journal":{"name":"Clinical and Experimental Medicine","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142268447","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Utility of serum uric acid levels in excluding pulmonary hypertension in severe chronic lung disease: insights from a tertiary care center 血清尿酸水平在排除重症慢性肺病肺动脉高压中的作用：来自一家三级医疗中心的启示

IF 4.6 4区医学

Clinical and Experimental Medicine Pub Date : 2024-09-13 DOI: 10.1007/s10238-024-01488-9

Shimon Izhakian, Alon Gorenshtein, Haya Engelstein, Lev Freidkin, Dror Rosengarten, Ofir Eldar, Mordechai R. Kramer

{"title":"Utility of serum uric acid levels in excluding pulmonary hypertension in severe chronic lung disease: insights from a tertiary care center","authors":"Shimon Izhakian, Alon Gorenshtein, Haya Engelstein, Lev Freidkin, Dror Rosengarten, Ofir Eldar, Mordechai R. Kramer","doi":"10.1007/s10238-024-01488-9","DOIUrl":"https://doi.org/10.1007/s10238-024-01488-9","url":null,"abstract":"Hyperuricemia is a known predictor of World Health Organization (WHO) Group 1 pulmonary hypertension (PH) (pulmonary arterial hypertension), but its role in excluding PH secondary to chronic lung diseases (WHO Group 3) remains unclear. We retrospectively analyzed data from 323 patients with severe chronic pulmonary diseases who underwent evaluation for lung transplantation at a tertiary medical center between June 2017 and February 2023. We examined the association between hyperuricemia (serum uric acid > 6 mg/dL or > 0.357 mmol/L) and PH [mean pulmonary arterial pressure (MPAP) > 20 mmHg]. Compared to the normouricemia group (n = 211), hyperuricemic patients (n = 112) were more likely to be younger (P = 0.02), male (P < 0.001), and present with PH (P = 0.001) and severe PH (MPAP > 35 mmHg; P < 0.001). These patients also had a higher body mass index (P = 0.004), plasma N-terminal pro-B-type natriuretic peptide (P < 0.001), serum creatinine (P < 0.001), and C-reactive protein levels (P = 0.03). Significant associations with PH included higher body mass index (P = 0.005), uric acid levels (P < 0.001), total lung capacity (P = 0.02), and residual volume (P = 0.01); shorter 6-min walk test distance (P = 0.005); and lower forced expiratory volume in one second (P = 0.006) and diffusing capacity for carbon monoxide (P < 0.001). Multivariate analysis showed elevated uric acid levels remained significantly associated with PH (OR 1.29, 95% CI 1.05–1.58, P = 0.01). In conclusion, normal serum uric acid levels serve as a significant predictor for excluding pulmonary hypertension in patients with severe chronic lung diseases.","PeriodicalId":10337,"journal":{"name":"Clinical and Experimental Medicine","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142250949","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Identification of PFKFB3 as a key factor in the development of colorectal cancer and immunotherapy resistance 确定 PFKFB3 是结直肠癌发展和免疫疗法耐药性的关键因素

IF 4.6 4区医学

Clinical and Experimental Medicine Pub Date : 2024-09-12 DOI: 10.1007/s10238-024-01479-w

Si Lu, Rongjie Zhao, Yicheng Han, Shengpeng Shao, Yaming Ji, Jinku Zhang, Hongming Pan, Jiachun Sun, Yuxiong Feng

{"title":"Identification of PFKFB3 as a key factor in the development of colorectal cancer and immunotherapy resistance","authors":"Si Lu, Rongjie Zhao, Yicheng Han, Shengpeng Shao, Yaming Ji, Jinku Zhang, Hongming Pan, Jiachun Sun, Yuxiong Feng","doi":"10.1007/s10238-024-01479-w","DOIUrl":"https://doi.org/10.1007/s10238-024-01479-w","url":null,"abstract":"Resistance to immunotherapy poses a significant challenge in the treatment of colorectal cancer (CRC), and the underlying mechanisms are not fully understood. Recent studies have implicated PFKFB3, a crucial glycolytic enzyme, in shaping the tumor microenvironment in CRC. Our study aimed to systematically study the role of PFKFB3 in CRC. Bioinformatic analysis revealed that PFKFB3 expression is notably elevated in CRC tissues compared to normal counterparts. In vivo experiments confirmed that suppressing PFKFB3 reduces the tumorigenesis of CRC. We identified multiple cancer-associated pathways positively correlated with high expression of PFKFB3, such as epithelial-mesenchymal transition (EMT), hypoxia, KRAS signaling, angiogenesis, PI3K/AKT/mTOR, Hedgehog, and Notch pathways. Additionally, PFKFB3 exhibited significant correlations with various immune-related pathways, including complement, IL-2/STAT5, IL-6/JAK/STAT3, IFN-α/IFN-γ, TGF-β, and TNF-α/NF-κB, as well as several immunosuppressive cell markers found in regulatory T cells (CCR8, TGFB1, STAT5B, FOXP3), M2 macrophages (CD163, VSIG4, MS4A4A), T cell exhaustion markers (CTLA-4, PDCD1, LAG3), and PD-L1. Intriguingly, increased PFKFB3 expression was observed in PD-L1 blockade-resistant patients and was associated with shorter overall survival. In a nutshell, PFKFB3 plays an important role in CRC tumorigenesis and resistance to immunotherapy. Targeting PFKFB3 inhibits tumor formation and enhances the efficacy of immunotherapy. Our findings underscore the functions of PFKFB3 in CRC, shedding light on both cancer-related and immunosuppressive pathways.","PeriodicalId":10337,"journal":{"name":"Clinical and Experimental Medicine","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142194669","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0