Peng Ye, Shahang Luo, Junyu Huang, Xihua Fu, Xiaoxia Chi, Jong-Ho Cha, Yumei Chen, Yanjun Mai, Kai-Wen Hsu, Xiuwen Yan, Wen-Hao Yang
{"title":"TESC associated with poor prognosis enhances cancer stemness and migratory properties in liver cancer.","authors":"Peng Ye, Shahang Luo, Junyu Huang, Xihua Fu, Xiaoxia Chi, Jong-Ho Cha, Yumei Chen, Yanjun Mai, Kai-Wen Hsu, Xiuwen Yan, Wen-Hao Yang","doi":"10.1007/s10238-024-01469-y","DOIUrl":"10.1007/s10238-024-01469-y","url":null,"abstract":"<p><p>Liver cancer stem cells (LCSCs) are responsible for recurrence, metastasis, and drug resistance in liver cancer. However, the genes responsible for inducing LCSCs have not been fully identified. Based on our previous study, we found that tescalcin (TESC), a calcium-binding EF hand protein that plays a crucial role in chromatin remodeling, transcriptional regulation, and epigenetic modifications, was up-regulated in LCSCs of spheroid cultures. By searching the Cancer Genome Atlas, International Cancer Genome Consortium, Human Protein Atlas, and Kaplan-Meier Plotter databases, we found that TESC expression was significantly elevated in liver cancer compared with that in normal liver tissue and was predictive of a decreased overall survival rate. Multivariate Cox analysis revealed TESC to be an independent prognostic factor for survival. High TESC expression was positively associated with cancer stem cell pathways, cancer stem cell surface markers, stemness transcription factors, epithelial-mesenchymal transition (EMT) factors, immune checkpoint proteins, and various cancer-related biological processes in liver cancer. Furthermore, TESC was implicated as promoting cancer stem cell properties through its influence on EMT. We demonstrated that TESC is a novel stemness-related gene that can serve as an independent prognostic factor for liver cancer.</p>","PeriodicalId":10337,"journal":{"name":"Clinical and Experimental Medicine","volume":"24 1","pages":"206"},"PeriodicalIF":3.2,"publicationDate":"2024-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11362204/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142104937","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}
{"title":"Oncolytic virus and tumor-associated macrophage interactions in cancer immunotherapy.","authors":"Marc Lecoultre, Paul R Walker, Aya El Helali","doi":"10.1007/s10238-024-01443-8","DOIUrl":"10.1007/s10238-024-01443-8","url":null,"abstract":"<p><p>Oncolytic viruses (OV) are a promising strategy in cancer immunotherapy. Their capacity to promote anti-tumoral immunity locally raises hope that cancers unresponsive to current immunotherapy approaches could be tackled more efficiently. In this context, tumor-associated macrophages (TAM) must be considered because of their pivotal role in cancer immunity. Even though TAM tend to inhibit anti-tumoral responses, their ability to secrete pro-inflammatory cytokines and phagocytose cancer cells can be harnessed to promote therapeutic cancer immunity. OVs have the potential to promote TAM pro-inflammatory functions that favor anti-tumoral immunity. But in parallel, TAM pro-inflammatory functions induce OV clearance in the tumor, thereby limiting OV efficacy and highlighting that the interaction between OV and TAM is a double edge sword. Moreover, engineered OVs were recently developed to modulate specific TAM functions such as phagocytic activity. The potential of circulating monocytes to deliver OV into the tumor after intravenous administration is also emerging. In this review, we will present the interaction between OV and TAM, the potential of engineered OV to modulate specific TAM functions, and the promising role of circulating monocytes in OV delivery to the tumor.</p>","PeriodicalId":10337,"journal":{"name":"Clinical and Experimental Medicine","volume":"24 1","pages":"202"},"PeriodicalIF":3.2,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11358230/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142079357","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}
{"title":"Profile of immunological biomarkers in Behcet's syndrome: a large-scale single-center real-world study.","authors":"Jiachen Li, Feng Sun, Yingni Li, Jing Zhao, Rulin Jia, Hongyan Wang, Xiaohong Xiang, Xiaolin Sun, Chengbin Chen, Haixin Xu, Zhanguo Li, Tian Liu","doi":"10.1007/s10238-024-01462-5","DOIUrl":"10.1007/s10238-024-01462-5","url":null,"abstract":"<p><p>Behcet's syndrome (BS) is a vasculitis characterized by immune dysregulation. Biomarkers are valuable for assessing clinically atypical pathogenesis. We aimed to investigate the distribution of different biomarkers and their effects on the clinical features of patients with BS in a large-scale, real-world study. This is a retrospective, single-center study. In total, 502 patients diagnosed with BS were enrolled in this study. We analyzed the clinical features of this cohort and divided patients' symptoms into six categories, including mucocutaneous, articular, neurological, gastrointestinal, vascular, and ocular involvements. HLA-B51 cells, autoantibodies, and subsets of immune cells from the patients were tested. Pearson's correlation, Wilcoxon rank sum test and multivariate logistic regression were used for data analysis. Various autoantibodies were detected in the serum of 40.8% of patients with BS. The positivity rate of anti-endothelial cell antibodies (AECA) was the highest among autoantibodies and was found in 23.5% (118/502) of patients with BS. The positivity rate of HLA-B51 in patients with BS was 27.1%. Tumor necrosis factor (TNF)-α, IL-2, and IL-4 producing CD4<sup>+</sup> T cells were positively correlated with the gastrointestinal BS. Increased IL-4<sup>+</sup>CD4<sup>+</sup> T cell was a risk factor for gastrointestinal BS (P = 0.006, Overall rate [OR] = 2.491, 95% Confidence interval [CI]: [1.317, 5.100]). Various autoantibodies can be detected in patients with BS. HLA-B51 and AECA are the most common biomarkers. Increased IL-4<sup>+</sup> CD4<sup>+</sup> T cell was a risk factor for gastrointestinal involvement in BS.</p>","PeriodicalId":10337,"journal":{"name":"Clinical and Experimental Medicine","volume":"24 1","pages":"201"},"PeriodicalIF":3.2,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11358242/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142079358","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}
{"title":"Advances in nucleic acid therapeutics: structures, delivery systems, and future perspectives in cancer treatment.","authors":"Leqi Zhang, Wenting Lou, Jianwei Wang","doi":"10.1007/s10238-024-01463-4","DOIUrl":"10.1007/s10238-024-01463-4","url":null,"abstract":"<p><p>Cancer has emerged as a significant threat to human health. Nucleic acid therapeutics regulate the gene expression process by introducing exogenous nucleic acid fragments, offering new possibilities for tumor remission and even cure. Their mechanism of action and high specificity demonstrate great potential in cancer treatment. However, nucleic acid drugs face challenges such as low stability and limited ability to cross physiological barriers in vivo. To address these issues, various nucleic acid delivery vectors have been developed to enhance the stability and facilitate precise targeted delivery of nucleic acid drugs within the body. In this review article, we primarily introduce the structures and principles of nucleic acid drugs commonly used in cancer therapy, as well as their cellular uptake and intracellular transportation processes. We focus on the various vectors commonly employed in nucleic acid drug delivery, highlighting their research progress and applications in recent years. Furthermore, we propose potential trends and prospects of nucleic acid drugs and their carriers in the future.</p>","PeriodicalId":10337,"journal":{"name":"Clinical and Experimental Medicine","volume":"24 1","pages":"200"},"PeriodicalIF":3.2,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11358240/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142079425","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}
Cheng Fan, Mengyuan Guo, Shuye Chang, Zhaohui Wang, Tianhui An
{"title":"Elevated TyG-BMI index predicts incidence of chronic kidney disease.","authors":"Cheng Fan, Mengyuan Guo, Shuye Chang, Zhaohui Wang, Tianhui An","doi":"10.1007/s10238-024-01472-3","DOIUrl":"10.1007/s10238-024-01472-3","url":null,"abstract":"<p><p>Chronic kidney disease (CKD) represents a significant global public health issue, with its incidence and prevalence escalating annually. Metabolic disorders are one of the major etiological factors of CKD. This study investigates the relationship between the emerging metabolic index triglyceride-glucose body mass index (TyG-BMI) and the onset of CKD. Our study enrolled 3,485 healthy participants (1,576 men and 1,909 women), with a follow-up period of 3 years. The primary outcome was the emergence of CKD, defined by an eGFR less than 60 mL/(min × 1.73 m<sup>2</sup>) or the onset of proteinuria. To examine the TyG-BMI and CKD onset relationship, we used univariate and multivariate logistic regression analyses, stratified analyses, and receiver operating characteristic (ROC) curves. After a three-year follow-up, CKD developed in 2% (n = 70) of the participants. Subjects were divided into three equal groups based on their TyG-BMI values, from lowest to highest. After adjusting for potential confounders, the highest TyG-BMI group exhibited a multifactor-adjusted odds ratio (OR) of 4.24 (95% CI 1.30-13.78, P = 0.016) compared to the lowest group. Stratified analyses revealed that the association between TyG-BMI and CKD onset was stronger among females, individuals younger than 60 years, and those with a BMI ≥ 24 kg/m<sup>2</sup>. Furthermore, TYG-BMI was effective in predicting the incidence of CKD. Our findings indicate that TyG-BMI is an independent risk factor for the onset of CKD and that assessment of TyG-BMI may be useful for the early identification of individuals at high risk for CKD.</p>","PeriodicalId":10337,"journal":{"name":"Clinical and Experimental Medicine","volume":"24 1","pages":"203"},"PeriodicalIF":3.2,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11358226/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142079355","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}
Shanshan Chen, Fusheng Gong, Shijia Liu, Yunqing Xie, Xingming Ye, Xiaowei Lin, Xiangru Wang, Qiuhong Zheng, Qinying Liu, Yang Sun
{"title":"IL-21- and CXCL9-engineered GPC3-specific CAR-T cells combined with PD-1 blockade enhance cytotoxic activities against hepatocellular carcinoma.","authors":"Shanshan Chen, Fusheng Gong, Shijia Liu, Yunqing Xie, Xingming Ye, Xiaowei Lin, Xiangru Wang, Qiuhong Zheng, Qinying Liu, Yang Sun","doi":"10.1007/s10238-024-01473-2","DOIUrl":"10.1007/s10238-024-01473-2","url":null,"abstract":"<p><p>The application of CAR-T cells in solid tumors poses several challenges, including poor T cell homing ability, limited infiltration of T cells and an immunosuppressive tumor environment. In this study, we developed a novel approach to address these obstacles by designing GPC3-specific CAR-T cell that co-express IL-21 and CXCL9 (21 × 9 GPC3 CAR-T cells) and blocking the PD-1 expression on it. The proliferation, cell phenotype, cytokine secretion and cell migration of indicated CAR-T cells were evaluated in vitro. The cytotoxic activities of genetically engineered CAR-T cells were accessed in vitro and in vivo. Compared to conventional GPC3 CAR-T cells, the 21 × 9 GPC3 CAR-T cells demonstrated superior proliferation, cytokine secretion and chemotaxis capabilities in vitro. Furthermore, when combined with PD-1 blockade, the 21 × 9 GPC3 CAR-T cells exhibited enhanced proliferation, cytokine secretion and enrichment of effector T cells such as CTL, NKT and TEM cells. In xenograft tumor models, the PD-1 blocked 21 × 9 GPC3 CAR-T cells effectively suppressed HCC xenograft growth and increased T cell infiltration. Overall, our study successfully generated GPC3 CAR-T cells expressing both IL-21 and CXCL9, demonstrated that combining PD-1 blockade can further enhance CAR-T cell function by promoting proliferation, cytokine secretion, chemotaxis and antitumor activity. These findings present a hopeful and potentially effective strategy for GPC3-positive HCC patients.</p>","PeriodicalId":10337,"journal":{"name":"Clinical and Experimental Medicine","volume":"24 1","pages":"204"},"PeriodicalIF":3.2,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11358300/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142079356","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}
Teng Ji, Yuchuan Liu, Yutong Li, Chuanfen Li, Yingyan Han
{"title":"Viral vector-based therapeutic HPV vaccines.","authors":"Teng Ji, Yuchuan Liu, Yutong Li, Chuanfen Li, Yingyan Han","doi":"10.1007/s10238-024-01470-5","DOIUrl":"10.1007/s10238-024-01470-5","url":null,"abstract":"<p><p>Replication-defective viral vector vaccines have several advantages over conventional subunit vaccines, including potent antibody responses, cellular responses critical for eliminating pathogen-infected cells, and the induction of highly immunogenic and durable immune responses without adjuvants. The Human papillomavirus (HPV), a microorganism with over 200 genotypes, plays a crucial role in inducing human tumors, with the majority of HPV-related malignancies expressing HPV proteins. Tumors associated with HPV infection, most of which result from HPV16 infection, include those affecting the cervix, anus, vagina, penis, vulva, and oropharynx. In recent years, the development of therapeutic HPV vaccines utilizing viral vectors for the treatment of premalignant lesions or tumors caused by HPV infection has experienced rapid growth, with numerous research pipelines currently underway. Simultaneously, screening for optimal antigens requires more basic research and more optimized methods. In terms of preclinical research, we present the various models used to assess vaccine efficacy, highlighting their respective advantages and disadvantages. Further, we present current research status of therapeutic vaccines using HPV viral vectors, especially the indications, initial efficacy, combination drugs, etc. In general, this paper summarizes current viral vector therapeutic HPV vaccines in terms of HPV infection, antigen selection, vectors, efficacy evaluation, and progress in clinical trials.</p>","PeriodicalId":10337,"journal":{"name":"Clinical and Experimental Medicine","volume":"24 1","pages":"199"},"PeriodicalIF":3.2,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11358221/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142079446","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}
Dor Shpitzer, Yael C Cohen, Chava Perry, Guy Melamed, Hillel Alapi, Anat Reiner-Benaim, Irit Avivi
{"title":"Clinical significance of FLC tests in patients without other evidence of hematologic disorder.","authors":"Dor Shpitzer, Yael C Cohen, Chava Perry, Guy Melamed, Hillel Alapi, Anat Reiner-Benaim, Irit Avivi","doi":"10.1007/s10238-024-01471-4","DOIUrl":"10.1007/s10238-024-01471-4","url":null,"abstract":"<p><p>The clinical significance of an abnormal free light chain (FLC) test, performed due to unspecific complains in the absence of a known plasma cell dyscrasia (PCD) or lymphoproliferative disease (LPD), is not fully elucidated. We investigated the importance of an abnormal FLC ratio (FLC-R) in this setting. Patients registered in the Maccabi Healthcare Services database, tested for FLC during 2007-2023 without previously documented PCD/LPD or increased total protein (TP) level, were reviewed. Demographics, co-morbidities, and laboratory tests were recorded. FLC-R was defined as normal (0.26-1.65) or slightly (slAb 0.1-0.26/1.65-4), moderately (mAbn 0.1-0.05/4-8) and significantly abnormal (sigAb- < 0.05 or > 8). Factors associated with PCD/LPD and overall survival were identified. In total, 8,661 patients, 2,215 (25.6%) with abnormal FLC-R [2,090 (24.1%)-slAb, 65 (0.75%)-mAbn and 60 (0.7%)-sigAb], were analyzed. Almost none had anemia nor acute renal failure. 14% had concomitant increased immunoglobulins. Within a median follow-up of 52 months, 943 were diagnosed with PCD (816-MGUS, 127-MM/Amyloidosis/plasmacytoma) and 48 with LPD. Median time to PCD and LPD were 19 and 28 months. Multivariate analysis found slAb (HR = 1.8, CI95%:1.53-2.12, p < 0.001), mAbn (HR = 6.3, CI95%:4.16-9.53, p < 0.001), and sigAb FLC (HR = 10.4, CI95%:7.0-15.35, p < 0.001), to be associated with PCD/LPD diagnosis. Decreased IgG, increased IgA, and concomitant comorbidities predicted PCD, whereas increased IgM predicted LPD. Older age, male gender, anemia, decreased albumin, increased IgG and concomitant comorbidities, predicted shorter survival. Our large study emphasizes the independent clinical significance of abnormal FLC-R as a predictor of PCD/LPD diagnosis even in patients with normal TP level, promoting early detection of PCD/LPD.</p>","PeriodicalId":10337,"journal":{"name":"Clinical and Experimental Medicine","volume":"24 1","pages":"198"},"PeriodicalIF":3.2,"publicationDate":"2024-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11344700/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142046375","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}
{"title":"Sysmex XN-HPC: study of reference intervals and clinical decision limits in healthy allogeneic donors mobilised with G-CSF.","authors":"Lunhui Huang, Binbin Lin, Yueyi Mu, Yong Li, Miao Chen, Yunxia Zhou, Guoqing Zhu, Erlie Jiang, Yonghui Xia","doi":"10.1007/s10238-024-01467-0","DOIUrl":"10.1007/s10238-024-01467-0","url":null,"abstract":"<p><p>The Sysmex XN series haematopoietic progenitor cell (XN-HPC) is a novel tool for assessing stem cell yield before allogeneic haematopoietic stem cell transplantation. This study aimed to establish a reference interval (RI) for XN-HPC in peripheral blood allogeneic transplant donors following granulocyte colony-stimulating factor (G-CSF) stimulation and determine its clinical significance. All specimens were analysed using Sysmex XN-20. Samples were collected and analysed using non-parametric percentile methods to define the RIs. Quantile regression was used to explore the dependency of the RIs on sex and age. Samples were included in clinical decision limits for apheresis based on receiver operating characteristic curve analysis. The non-parametrically estimated RI for XN-HPC was 623.50 (90% confidence interval [CI90%] 510.00-657.00) to 4,144.28 (CI90% 3,761.00-4,547.00). The RIs for the XN-HPC were not age-dependent but were sex-dependent. The RI for males was 648.40 (CI90% 582.00-709.00)-4,502.60 (CI90% 4,046.00-5,219.00) and for females was 490.90 (CI90% 311.00-652.00)-3,096.90 (CI90% 2,749.00-3,782.00). Comparisons based on XN-HPC values between the poor and less-than-optimal groups, good and less-than-optimal groups, and good and non-good groups had areas under the curve of 0.794 (P < 0.001), 0.768 (P < 0.001), and 0.806 (P < 0.001), respectively, indicating a good predictive value for mobilisation effectiveness. XN-HPC data exceeding 3974 × 10<sup>6</sup>/L suggested that a sufficient number of stem cells could be collected clinically. Values > 5318 < 10<sup>6</sup>/L indicated 100% mobilisation effectiveness. We established an RI for XN-HPC in peripheral blood allogeneic transplant donors following G-CSF stimulation and determined clinical decision thresholds for mobilisation efficiency.</p>","PeriodicalId":10337,"journal":{"name":"Clinical and Experimental Medicine","volume":"24 1","pages":"197"},"PeriodicalIF":3.2,"publicationDate":"2024-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11344708/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142046376","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}