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Association of CAR-T approval on outcomes in patients with diffuse large B-cell lymphoma at the population level in the United States. CAR-T批准与美国人群水平弥漫性大b细胞淋巴瘤患者预后的关联
IF 9.5 2区 医学
Biomarker Research Pub Date : 2025-04-24 DOI: 10.1186/s40364-025-00780-4
John L Vaughn, Angela Ramdhanny, Malak Munir, Sravani Rimmalapudi, Narendranath Epperla
{"title":"Association of CAR-T approval on outcomes in patients with diffuse large B-cell lymphoma at the population level in the United States.","authors":"John L Vaughn, Angela Ramdhanny, Malak Munir, Sravani Rimmalapudi, Narendranath Epperla","doi":"10.1186/s40364-025-00780-4","DOIUrl":"https://doi.org/10.1186/s40364-025-00780-4","url":null,"abstract":"<p><p>While the advent of chimeric antigen receptor T-cell (CAR-T) therapy has revolutionized the treatment of relapsed or refractory DLBCL, it is unclear how survival has changed at the population level following its approval. Herein, we performed a population-based cohort study using the SEER-17 database. The primary exposure was a period of diagnosis (2014-2017 vs. 2018-2021), and these periods were selected based on the first FDA-approval of CAR-T in 2017. Study outcomes were relative survival (RS), overall survival (OS), lymphoma-specific survival (LSS), and the cumulative incidence of death from lymphoma (CIF). A total of 51,584 patients with DLBCL were included in the study with 24,861 patients diagnosed in time period-1 (2014-2017) and 26,723 patients diagnosed in time period-2 (2018-2021). The median age at diagnosis was 68 years (interquartile range, 57-77) and most patients were White (n = 42,190, 82%) with advanced stage at diagnosis (n = 28,203, 55%). In unadjusted analysis, the 5-year RS (95% CI) increased from 64% from 2014 to 2017 to 66% from 2018 to 2021, while 5-year OS increased from 54 to 55%, and 5-year LSS increased from 64 to 66%. On competing risks analysis, the 5-year probability of death from lymphoma decreased from 34 to 31%. The improvements in survival were observed across age, disease stage, and racial groups, and remained significant when adjusting for age, sex, race, stage, B symptoms and documented receipt of chemotherapy in multivariable survival models (adjusted OS HR = 0.97, 95%CI = 0.94-1.00, p = 0.04; adjusted LSS HR = 0.93, 95%CI = 0.90-0.96, p < 0.001). We found improved survival for patients with DLBCL diagnosed between 2018 and 2021 when compared to those diagnosed between 2014 and 2017. These findings will serve as the benchmark for future studies evaluating the impact of CAR-T administered earlier in their disease course.</p>","PeriodicalId":54225,"journal":{"name":"Biomarker Research","volume":"13 1","pages":"64"},"PeriodicalIF":9.5,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12023351/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144040325","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
Challenges and advances for huntingtin detection in cerebrospinal fluid: in support of relative quantification. 脑脊液中亨廷顿蛋白检测的挑战和进展:支持相对量化。
IF 9.5 2区 医学
Biomarker Research Pub Date : 2025-04-21 DOI: 10.1186/s40364-025-00772-4
Rachel J Harding, Yuanyun Xie, Nicholas S Caron, Hailey Findlay-Black, Caroline Lyu, Nalini Potluri, Renu Chandrasekaran, Michael R Hayden, Blair R Leavitt, Douglas R Langbehn, Amber L Southwell
{"title":"Challenges and advances for huntingtin detection in cerebrospinal fluid: in support of relative quantification.","authors":"Rachel J Harding, Yuanyun Xie, Nicholas S Caron, Hailey Findlay-Black, Caroline Lyu, Nalini Potluri, Renu Chandrasekaran, Michael R Hayden, Blair R Leavitt, Douglas R Langbehn, Amber L Southwell","doi":"10.1186/s40364-025-00772-4","DOIUrl":"https://doi.org/10.1186/s40364-025-00772-4","url":null,"abstract":"<p><p>Huntington disease (HD) is a progressive and devastating neurodegenerative disease caused by expansion of a glutamine-coding CAG tract in the huntingtin (HTT) gene above a critical threshold of ~ 35 repeats resulting in expression of mutant HTT (mHTT). A promising treatment approach being tested in clinical trials is HTT lowering, which aims to reduce levels of the mHTT protein. Target engagement of these therapies in the brain are inferred using antibody-based assays that measure mHTT levels in the cerebrospinal fluid (CSF). These levels are typically reported as the absolute concentration of mHTT concentration, derived from a standard curve generated using a single protein standard. However, patient biofluids are a complex milieu containing different mHTT protein species, suggesting that absolute quantitation is challenging. As a result, a single recombinant protein standard may not be sufficient to interpret assay signal as molar mHTT concentration. In this study, we used immunoprecipitation and flow cytometry (IP-FCM) to investigate different factors that influence mHTT detection assay signal. Our results show that HTT protein fragmentation, protein-protein interactions, affinity tag positioning, oligomerization and polyglutamine tract length affect assay signal intensity. These findings indicate that absolute HTT quantitation in heterogeneous biological samples is not possible with current technologies using a single standard protein. We also explore the binding specificity of the MW1 anti-polyglutamine antibody, commonly used in these assays as a mHTT-selective reagent and demonstrate that mHTT binding is preferred but not specific. Furthermore, we find that MW1 depletion of mHTT for quantitation of wildtype HTT is not only incomplete, leaving residual mHTT, but also non-specific, resulting in pull down of some wildtype HTT protein. Based on these observations, we recommend that mHTT detection assays report only relative mHTT quantitation using normalized arbitrary units of assay signal intensity, rather than molar concentrations, in the assessment of central nervous system HTT lowering in ongoing clinical and preclinical studies. Further, we recommend that MW1-depletion not be used as a method for quantifying wildtype HTT protein and that detergent be consistently added to samples during testing.</p>","PeriodicalId":54225,"journal":{"name":"Biomarker Research","volume":"13 1","pages":"63"},"PeriodicalIF":9.5,"publicationDate":"2025-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12012996/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144041140","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
Decoding tumor angiogenesis: pathways, mechanisms, and future directions in anti-cancer strategies. 解码肿瘤血管生成:抗癌策略的途径、机制和未来方向。
IF 9.5 2区 医学
Biomarker Research Pub Date : 2025-04-18 DOI: 10.1186/s40364-025-00779-x
Xueru Liu, Juan Zhang, Ting Yi, Hui Li, Xing Tang, Dan Liu, Daichao Wu, Yukun Li
{"title":"Decoding tumor angiogenesis: pathways, mechanisms, and future directions in anti-cancer strategies.","authors":"Xueru Liu, Juan Zhang, Ting Yi, Hui Li, Xing Tang, Dan Liu, Daichao Wu, Yukun Li","doi":"10.1186/s40364-025-00779-x","DOIUrl":"https://doi.org/10.1186/s40364-025-00779-x","url":null,"abstract":"<p><p>Angiogenesis, a crucial process in tumor growth and metastasis, necessitates targeted therapeutic intervention. This review reviews the latest knowledge of anti-angiogenesis targets in tumors, with emphasis on the molecular mechanisms and signaling pathways that regulate this process. We emphasize the tumor microenvironment's role in angiogenesis, examine endothelial cell metabolic changes, and evaluated potential therapeutic strategies targeting the tumor vascular system. At the same time, we analyzed the signaling pathway and molecular mechanism of tumor angiogenesis in detail. In addition, this paper also looks at the development trend of tumor anti-angiogenesis drugs, including their future development direction and challenges, aiming to provide prospective insight into the development of this field. Despite their potential, anti-angiogenic therapies encounter challenges like drug resistance and side effects, necessitating ongoing research to enhance cancer treatment strategies and the efficacy of these therapies.</p>","PeriodicalId":54225,"journal":{"name":"Biomarker Research","volume":"13 1","pages":"62"},"PeriodicalIF":9.5,"publicationDate":"2025-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12007322/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144026088","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
IL1RAP is an immunotherapeutic target for normal karyotype triple-mutated acute myeloid leukemia. IL1RAP是正常核型三突变急性髓系白血病的免疫治疗靶点。
IF 9.5 2区 医学
Biomarker Research Pub Date : 2025-04-14 DOI: 10.1186/s40364-025-00769-z
Arnaud Métois, Marie-Eve Bordeleau, Louis Theret, Azadeh Hajmirza, Ossama Moujaber, Jean-François Spinella, Jalila Chagraoui, Nadine Mayotte, Isabel Boivin, Éric Audemard, Léo Aubert, Véronique Lisi, Banafsheh Khakipoor, Azer Farah, Éric Bonneil, Alma Robert, Julie Lippens, Anna Moraitis, François Béliveau, Albert Feghaly, Geneviève Boucher, Richard Marcotte, Patrick Gendron, Pierre Thibault, Sébastien Lemieux, Guillaume Richard-Carpentier, Vincent-Philippe Lavallée, Josée Hébert, Philippe P Roux, Guy Sauvageau
{"title":"IL1RAP is an immunotherapeutic target for normal karyotype triple-mutated acute myeloid leukemia.","authors":"Arnaud Métois, Marie-Eve Bordeleau, Louis Theret, Azadeh Hajmirza, Ossama Moujaber, Jean-François Spinella, Jalila Chagraoui, Nadine Mayotte, Isabel Boivin, Éric Audemard, Léo Aubert, Véronique Lisi, Banafsheh Khakipoor, Azer Farah, Éric Bonneil, Alma Robert, Julie Lippens, Anna Moraitis, François Béliveau, Albert Feghaly, Geneviève Boucher, Richard Marcotte, Patrick Gendron, Pierre Thibault, Sébastien Lemieux, Guillaume Richard-Carpentier, Vincent-Philippe Lavallée, Josée Hébert, Philippe P Roux, Guy Sauvageau","doi":"10.1186/s40364-025-00769-z","DOIUrl":"https://doi.org/10.1186/s40364-025-00769-z","url":null,"abstract":"<p><strong>Background: </strong>Surface antigens of potential clinical significance remain under-characterized in AML. The European Leukemia Network classifies normal karyotype AML (NK-AML) mutated for NPM1 (NPM1c) as a distinct entity associated with favorable outcomes if not associated with FLT3-ITD mutation. A subset of NPM1c NK-AML shows additional mutations in 2 genes: FLT3 (FLT3-ITD) and DNMT3 A. These leukemias, also referred to as NK triple mutated AML (NKt-AML), are particularly difficult to eradicate with current treatment options. Therefore, novel therapies are necessary that use proteins specifically expressed at the surface.</p><p><strong>Methods: </strong>In order to identify surface antigens for immunotherapy in NKt-AML, an extensive multi-omic analysis was conducted on primary AML samples. Surface proteome enrichment was performed on 100 primary AML samples, twelve of which were NKt-AML. Transcriptome analysis was carried out on the 691 primary AML samples, and single-cell RNA sequencing was conducted on 23 primary AML samples.</p><p><strong>Results: </strong>Herein, using multi-omics data from the Leucegene collection, we identify IL1RAP as a promising antigen for this AML subgroup. We demonstrate that IL1RAP is expressed at the surface of primitive AML cells reminiscent of leukemic stem cells in NKt-AML primary human AML specimens, while showing relatively low expression levels in normal bone marrow HSCs. Furthermore, results indicate that elevated IL1RAP expression associates with poor overall and relapse-free survival in the Leucegene cohort of AML patients and predicts nonresponse to hematopoietic stem cell transplantation. Finally, we show that IL1RAP protein is internalized following exposure to specific antibodies, suggesting that IL1RAP represents an interesting target for antibody-drug conjugate development in NKt-AML.</p><p><strong>Conclusions: </strong>IL1RAP exhibits preferential expression within NKt-AML, correlating with diminished overall survival rates and diminished responsiveness to hematopoietic stem cell transplantation. Moreover, internalization of IL1RAP presents a promising avenue for immunotherapeutic intervention.</p>","PeriodicalId":54225,"journal":{"name":"Biomarker Research","volume":"13 1","pages":"61"},"PeriodicalIF":9.5,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11995633/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144040472","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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 evolving landscape of biomarkers for systemic therapy in advanced hepatocellular carcinoma. 晚期肝细胞癌全身治疗生物标志物的发展前景。
IF 9.5 2区 医学
Biomarker Research Pub Date : 2025-04-12 DOI: 10.1186/s40364-025-00774-2
Xinyu Guo, Zhongwei Zhao, Lingyi Zhu, Shuang Liu, Lingling Zhou, Fazong Wu, Shiji Fang, Minjiang Chen, Liyun Zheng, Jiansong Ji
{"title":"The evolving landscape of biomarkers for systemic therapy in advanced hepatocellular carcinoma.","authors":"Xinyu Guo, Zhongwei Zhao, Lingyi Zhu, Shuang Liu, Lingling Zhou, Fazong Wu, Shiji Fang, Minjiang Chen, Liyun Zheng, Jiansong Ji","doi":"10.1186/s40364-025-00774-2","DOIUrl":"https://doi.org/10.1186/s40364-025-00774-2","url":null,"abstract":"<p><p>Hepatocellular carcinoma (HCC) remains one of the most prevalent and deadliest cancers. With the approval of multiple first- and second-line agents, especially the combination therapies based on immune checkpoint inhibitor (ICI) regimens, the landscape of systemic therapy for advanced HCC (aHCC) is more diverse than ever before. The efficacy of current systemic therapies shows great heterogeneity in patients with aHCC, thereby identifying biomarkers for response prediction and patient stratification has become an urgent need. The main biomarkers for systemic therapy in hepatocellular carcinoma are derived from peripheral blood, tissues, and imaging. Currently, the understanding of the clinical response to systemic therapy indicates unequivocally that a single biomarker cannot be used to identify patients who are likely to benefit from these treatments. In this review, we provide an integrated landscape of the recent development in molecular targeted therapies and ICIs-based therapies, especially focusing on the role of clinically applicable predictive biomarkers. Additionally, we further highlight the latest advancements in biomarker-driven therapies, including targeted treatments, adoptive cell therapies, and bispecific antibodies.</p>","PeriodicalId":54225,"journal":{"name":"Biomarker Research","volume":"13 1","pages":"60"},"PeriodicalIF":9.5,"publicationDate":"2025-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11993949/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144008197","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
Targeting myeloid cells for hematological malignancies: the present and future. 靶向骨髓细胞治疗血液恶性肿瘤:现在和未来。
IF 9.5 2区 医学
Biomarker Research Pub Date : 2025-04-10 DOI: 10.1186/s40364-025-00775-1
Zihui Guan, Zhengqi Zhang, Kaiyan Wang, Shukai Qiao, Teng Ma, Lina Wu
{"title":"Targeting myeloid cells for hematological malignancies: the present and future.","authors":"Zihui Guan, Zhengqi Zhang, Kaiyan Wang, Shukai Qiao, Teng Ma, Lina Wu","doi":"10.1186/s40364-025-00775-1","DOIUrl":"https://doi.org/10.1186/s40364-025-00775-1","url":null,"abstract":"<p><p>Hematological malignancies are a diverse group of cancers that originate in the blood and bone marrow and are characterized by the abnormal proliferation and differentiation of hematopoietic cells. Myeloid blasts, which are derived from normal myeloid progenitors, play a central role in these diseases by disrupting hematopoiesis and driving disease progression. In addition, other myeloid cells, including tumor-associated macrophages and myeloid-derived suppressor cells, adapt dynamically to the tumor microenvironment, where they can promote immune evasion and resistance to treatment. This review explores the unique characteristics and pathogenic mechanisms of myeloid blasts, the immunosuppressive roles of myeloid cells, and their complex interactions within the TME. Furthermore, we highlight emerging therapeutic approaches targeting myeloid cells, focusing on strategies to reprogram their functions, inhibit their suppressive effects, or eliminate pathological populations altogether, as well as the latest preclinical and clinical trials advancing these approaches. By integrating insights from these studies, we aim to provide a comprehensive understanding of the roles of myeloid cells in hematological malignancies and their potential as therapeutic targets.</p>","PeriodicalId":54225,"journal":{"name":"Biomarker Research","volume":"13 1","pages":"59"},"PeriodicalIF":9.5,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11983845/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144057540","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
Manipulation of cancer cell pyroptosis for therapeutic approaches: challenges and opportunities. 肿瘤细胞焦亡的治疗方法:挑战和机遇。
IF 9.5 2区 医学
Biomarker Research Pub Date : 2025-04-09 DOI: 10.1186/s40364-025-00771-5
Rui Miao, Xueying Wang, Jingyv Zhang, Qinyv Kang, Qing Liu, Xianglin Luo, Junwei Hou, Baorong Gao
{"title":"Manipulation of cancer cell pyroptosis for therapeutic approaches: challenges and opportunities.","authors":"Rui Miao, Xueying Wang, Jingyv Zhang, Qinyv Kang, Qing Liu, Xianglin Luo, Junwei Hou, Baorong Gao","doi":"10.1186/s40364-025-00771-5","DOIUrl":"10.1186/s40364-025-00771-5","url":null,"abstract":"<p><p>Remarkable advances have been achieved following discoveries that gasdermins are the executioners of pyroptosis. The pyroptotic process consists a subcellular permeabilization phase and a cell lysis phase, the latter of which is irreversible. Besides immune cells, pyroptosis has also been observed in cancer cells, which exhibit distinct mechanisms compared to canonical immune cell pyroptosis. Although chronic cancer cell pyroptosis fuels tumor growth, intense pyroptotic cell death in tumor cells enhances anticancer immunity by promoting killer lymphocytes infiltration. Triggering pyroptosis in cancer cells is emerging as a promising strategy for cancer treatment. In this review, we introduce the process of cancer cell pyroptosis and its role in antitumor immunity, discuss the translation of these insights into therapies, and highlight current challenges and opportunities in the investigation of cancer cell pyroptosis.</p>","PeriodicalId":54225,"journal":{"name":"Biomarker Research","volume":"13 1","pages":"58"},"PeriodicalIF":9.5,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11980353/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143813087","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
LRG1, a novel serum biomarker for iMCD disease activity. 一种新的iMCD疾病活动性血清生物标志物LRG1。
IF 9.5 2区 医学
Biomarker Research Pub Date : 2025-04-07 DOI: 10.1186/s40364-025-00767-1
Miao-Yan Zhang, Zi-Han Yang, Yu-Chong Qiu, Yu-Han Gao, Si-Yuan Li, Yue Dang, Lu Zhang, Jian Li
{"title":"LRG1, a novel serum biomarker for iMCD disease activity.","authors":"Miao-Yan Zhang, Zi-Han Yang, Yu-Chong Qiu, Yu-Han Gao, Si-Yuan Li, Yue Dang, Lu Zhang, Jian Li","doi":"10.1186/s40364-025-00767-1","DOIUrl":"10.1186/s40364-025-00767-1","url":null,"abstract":"<p><p>Idiopathic multicentric Castleman disease (iMCD) is a rare lymphoproliferative disorder characterized by systematic inflammatory symptoms and multiorgan dysfunction caused by a cytokine storm. The current assessment of treatment response in iMCD lack sensitivity due to the heterogeneity of clinical features. We performed proteomic analysis using Data Independent Acquisition (DIA) mass spectrometry (MS) on 33 serum samples in different disease states from 17 patients. Leucine-rich alpha-2-glycoprotein-1 (LRG1) emerged as one of the proteins with most significantly different expression, exhibiting lower levels in response to treatment. Enzyme-linked immunosorbent assay (ELISA) on a larger cohort of 146 serum samples (96 disease flare, 28 biochemical partial response, 22 biochemical complete response) from 100 iMCD patients further confirmed this association, demonstrating a significant decrease in serum LRG1 level following successful treatment. Notably, LRG1 remained elevated in patients with ongoing inflammation during siltuximab therapy when CRP failed to accurately reflect disease activity. Additionally, serum CRP/LRG1 ratio differed across iMCD subtypes, suggesting potential variations in inflammatory pathways. These findings support serum LRG1 as a valuable biomarker for iMCD disease treatment response and activity, and may provide insights into underlying disease mechanisms.</p>","PeriodicalId":54225,"journal":{"name":"Biomarker Research","volume":"13 1","pages":"56"},"PeriodicalIF":9.5,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11974158/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143803949","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
A novel indirubin- 3-monoxime derivative I3MV- 8b exhibits remarkable cytotoxicity against multiple myeloma by targeting TRIM28. 一种新的吲哚红- 3-单肟衍生物I3MV- 8b通过靶向TRIM28对多发性骨髓瘤表现出显著的细胞毒性。
IF 9.5 2区 医学
Biomarker Research Pub Date : 2025-04-07 DOI: 10.1186/s40364-025-00773-3
Teng Fang, Lanting Liu, Hao Sun, Xiaoyu Zhang, Xiyue Sun, Zhen Yu, Lixin Gong, Shiyi Xie, Yonglong Zhao, Yan Li, Lugui Qiu, Gang An, Bin He, Mu Hao
{"title":"A novel indirubin- 3-monoxime derivative I3MV- 8b exhibits remarkable cytotoxicity against multiple myeloma by targeting TRIM28.","authors":"Teng Fang, Lanting Liu, Hao Sun, Xiaoyu Zhang, Xiyue Sun, Zhen Yu, Lixin Gong, Shiyi Xie, Yonglong Zhao, Yan Li, Lugui Qiu, Gang An, Bin He, Mu Hao","doi":"10.1186/s40364-025-00773-3","DOIUrl":"10.1186/s40364-025-00773-3","url":null,"abstract":"<p><strong>Introduction: </strong>Maintaining protein homeostasis is vital for multiple myeloma (MM) cell survival. Indirubin- 3-monoxime (I3MO), a potential MM therapeutic, inhibits proteasome activity, while histone deacetylase 6 (HDAC6) regulates autophagy. We developed I3MV- 8b, an I3MO derivative, integrating an HDAC6 inhibitor moiety to enhance dual inhibition of proteasome and autophagy pathways.</p><p><strong>Methods: </strong>The anti-MM effects of I3MV- 8b were tested in vitro and in vivo. To identify downstream targets, RNA-seq and dual-luciferase reporter assays were performed. Additionally, ChIP-seq and IP-MS techniques were employed to elucidate the underlying molecular mechanism.</p><p><strong>Results: </strong>I3MV- 8b significantly suppressed MM cell proliferation and induced apoptosis. Combined with proteasome inhibitors, I3MV- 8b enhanced cytotoxicity by concurrently inhibiting proteasome and autophagy pathways. It reduced TRIM28 transcription, correlating with lower expression of proteasome subunits and autophagy-related genes. ChIP-seq revealed that TRIM28 binds to proteasome gene promoters, and its knockdown decreased proteasome subunit expression and activity. TRIM28 knockdown also impaired autophagosome formation. IP-MS and Co-IP assays showed TRIM28 interacted with 14-3 - 3ζ, a negative regulator of autophagy, promoting its ubiquitination and degradation. This interaction reduced autophagy regulation, further sensitizing cells to treatment.</p><p><strong>Conclusions: </strong>I3MV- 8b offers a novel dual inhibition strategy targeting proteasome and autophagy, presenting a promising therapeutic option for MM.</p>","PeriodicalId":54225,"journal":{"name":"Biomarker Research","volume":"13 1","pages":"57"},"PeriodicalIF":9.5,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11978164/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143803948","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
Development and validation of a predictive model based upon extracellular vesicle-derived transposable elements for non-invasive detection of pancreatic adenocarcinoma. 基于细胞外囊泡衍生转座因子的预测模型的开发和验证,用于无创检测胰腺腺癌。
IF 9.5 2区 医学
Biomarker Research Pub Date : 2025-04-05 DOI: 10.1186/s40364-025-00770-6
Yueting Liang, Xin Sui, Shuai Li, Haoxin Peng, Wenyi Jiang, Minqi Jia, Shaoran Jiang, Weihu Wang, Huajing Teng
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