Cancer letters最新文献

{"title":"Innate lymphoid cells in pancreatic ductal adenocarcinoma: Immune regulation and therapeutic implications","authors":"Tinghui Mao ,&nbsp;Wenjiao Teng ,&nbsp;Li Lin ,&nbsp;Wei Zhou","doi":"10.1016/j.canlet.2025.217890","DOIUrl":"10.1016/j.canlet.2025.217890","url":null,"abstract":"<div><div>Over the past two decades, immunotherapy has revolutionized cancer treatment by shifting our strategies to harness the body's own immune system, with the promise of inhibiting or even eliminating tumors through methods that control and enhance immune responses. Pancreatic ductal adenocarcinoma (PDAC), one of the most lethal malignancies, features an immunosuppressive tumor immune microenvironment (TIME) that serves as the core factor contributing to poor prognosis of patients. Emerging research has unveiled the dual role of innate lymphoid cells (ILCs), acting as tissue-resident innate immune hubs, in PDAC immune regulation through their dynamic plasticity, heterogeneity, and interactions with various adaptive immune cells. This review systematically summarizes the latest research advancements in the developmental plasticity of ILC subsets and their bidirectional regulatory network in PDAC, highlighting the potential value of targeting ILCs to reshape the PDAC TIME. Future research should integrate single-cell multi-omics technologies to dissect the spatiotemporal heterogeneity of ILCs, develop strategies to activate their anti-tumor activity, and explore synergistic approaches combining chimeric antigen receptor (CAR)-NK cell therapy with existing immunotherapies, providing new paradigms for transforming PDAC from an immunologically \"cold\" tumor to an immune-sensitive one.</div></div>","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":"629 ","pages":"Article 217890"},"PeriodicalIF":9.1,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144502789","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The significance of protein N-glycosylation in the pathogenesis of lung cancer and its clinical implications","authors":"Yibo Huang ,&nbsp;Jin Song ,&nbsp;Jinfeng Chen ,&nbsp;Feng Li ,&nbsp;Yi Zhang ,&nbsp;Jing-Hua Yang","doi":"10.1016/j.canlet.2025.217849","DOIUrl":"10.1016/j.canlet.2025.217849","url":null,"abstract":"<div><div>This comprehensive review systematically elucidates the multifaceted roles of protein N-glycosylation in lung cancer pathogenesis, including its contributions to accelerated cell proliferation, enhanced metastatic potential, promotion of epithelial‒mesenchymal transition (EMT), maintenance of stem cell characteristics, facilitation of immune evasion, preservation of angiogenesis, and diminished drug sensitivity. Additionally, the potential clinical utility of aberrant N-glycosylation is examined as a novel biomarker for early diagnosis, prognostic evaluation, and treatment monitoring in lung cancer. The analysis highlights the critical involvement of N-glycosylation in chemotherapy resistance, targeted therapy, and immunotherapy, offering new perspectives for the development of innovative therapeutic strategies. Furthermore, this review highlights promising applications of antibody-enzyme engineering technology in achieving more precise lung cancer treatments, introducing new opportunities for the field. These findings provide a significant theoretical basis and experimental evidence to support progress in lung cancer research and treatment advancements.</div></div>","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":"631 ","pages":"Article 217849"},"PeriodicalIF":9.1,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144511601","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CD51 promotes gastric cancer stemness via blocking Numb-mediated Notch1 degradation","authors":"Juzheng Peng ,&nbsp;Yuehan Yin ,&nbsp;Xuan Liu ,&nbsp;Cuncan Deng ,&nbsp;Peizhu Wang ,&nbsp;Xiaojie Hu ,&nbsp;Jiefu Chen ,&nbsp;Sicheng Peng ,&nbsp;Kuan Li ,&nbsp;Li Zhong ,&nbsp;Zhijun Zhou ,&nbsp;Yulong He ,&nbsp;Jiancheng Wang","doi":"10.1016/j.canlet.2025.217886","DOIUrl":"10.1016/j.canlet.2025.217886","url":null,"abstract":"<div><div>Gastric cancer (GC) remains a lethal malignancy with poor prognosis largely due to cancer stem cell (CSC)-driven metastasis, recurrence, and chemoresistance. This study identifies CD51 (integrin αv) as a pivotal regulator of GC stemness and malignant progression. Bioinformatics analysis of TCGA data revealed significant CD51 upregulation in GC tissues, correlating with advanced tumor stage and poor survival. Functional assays demonstrated that CD51 enhances CSC properties, including tumorsphere formation, migration, invasion, and oxaliplatin resistance. Mechanistically, CD51 interacts with Numb, a negative regulator of Notch signaling, to divert Notch1 receptor trafficking from lysosomal degradation to plasma membrane recycling, thereby amplifying Notch pathway activation. Single-cell RNA sequencing and clinical validations confirmed CD51's superior correlation with stemness scores compared to canonical CSC markers. Pharmacological inhibition of CD51 using cilengitide suppressed CSC phenotypes in vitro and inhibited tumor growth in patient-derived organoids and xenograft models. These findings establish CD51 as a novel CSC biomarker and therapeutic target, offering a strategy to disrupt Notch-dependent stemness and chemoresistance in GC.</div></div>","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":"629 ","pages":"Article 217886"},"PeriodicalIF":9.1,"publicationDate":"2025-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144483247","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mechanisms and therapeutic implications of glioma-neuron interactions","authors":"Yinyan Wang ,&nbsp;Yang Wang ,&nbsp;Hongbo Bao ,&nbsp;Zihan Wang ,&nbsp;Tao Jiang","doi":"10.1016/j.canlet.2025.217884","DOIUrl":"10.1016/j.canlet.2025.217884","url":null,"abstract":"<div><div>Glioma is the most common type of primary brain tumor and is almost always fatal. The challenge to develop more effective treatments lies in its high invasiveness and solid intratumoral heterogeneity, as well as its insensitivity to traditional radiotherapy and chemotherapy. With the rise of cancer neuroscience, mounting evidence has uncovered a multi-layered and dynamically complex network of communication between glioma cells and neurons which has given us new insights into tumor progression. The nervous system is now recognized as not merely a passive victim of tumor invasion, but as an active modulator and perhaps even driver of glioma progression. In this review, we systematically summarize the interaction of glioma with neuron mechanisms, including synaptic, electrophysiological, paracrine, metabolic, and neurotransmitter-related pathways. In addition, we investigate the extent to which these interactions are associated with gliomas and reveal their potential as therapeutic targets, thereby offering a theoretical foundation and new strategies for the precision treatment of glioma. Taken together, the cross-talk between gliomas and neurons is a dynamic, multi-level, multi-pathway co-regulated network system. Further exploration of this network may promote transformation from a tumor-focused to a tumor-neuron network-based therapeutic plan and provide new prospects for precision medicine.</div></div>","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":"629 ","pages":"Article 217884"},"PeriodicalIF":9.1,"publicationDate":"2025-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144367929","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An old spice with new tricks: Curcumin targets adenoma and colorectal cancer stem-like cells associated with poor survival outcomes","authors":"Sam Khan ,&nbsp;Ankur Karmokar ,&nbsp;Lynne Howells ,&nbsp;Robert G. Britton ,&nbsp;Emma Parrott ,&nbsp;Raquel Palacios-Gallego ,&nbsp;Cristina Tufarelli ,&nbsp;Hong Cai ,&nbsp;Jennifer Higgins ,&nbsp;Nicolas Sylvius ,&nbsp;Kevin West ,&nbsp;Angus McGregor ,&nbsp;David Moore ,&nbsp;Selena G. Burgess ,&nbsp;Mark W. Richards ,&nbsp;Anja Winter ,&nbsp;Zahirah Sidat ,&nbsp;Nalini Foreman ,&nbsp;Sanne T. Hoorn ,&nbsp;Louis Vermeulen ,&nbsp;Karen Brown","doi":"10.1016/j.canlet.2025.217885","DOIUrl":"10.1016/j.canlet.2025.217885","url":null,"abstract":"<div><div>The cost of cancer care globally is unsustainable and strategies to reduce the mounting burden of cancer are urgently needed. One approach is the use of preventive therapies to reduce cancer risk; dietary-derived compounds with good safety profiles represent a promising source of potential candidates but translating encouraging preclinical data to successful trials presents significant challenges. Development of curcumin, from the spice turmeric, as a preventive therapy for colorectal cancer (CRC) is hindered by poor understanding of its mechanism of action. Using patient derived xenografts and <em>ex-vivo</em> 3D-models exposed to clinically achievable curcumin concentrations, we found that it targets proliferating cancer stem-like cells (CSCs) within premalignant adenoma and early-stage cancer tissues, with broad spectrum activity across all molecular subtypes. Transcriptomics analysis revealed that curcumin pushes CSCs towards differentiation over self-renewal, thereby inhibiting tumour development. Evidence suggests these effects involve direct protein binding of curcumin to NANOG, a master regulator of CRC CSCs, and impairment of its transcriptional activity via direct interference with NANOG-DNA binding. Furthermore, curcumin decreased the proportion of proliferating CSCs, defined by NANOG/Ki67 co-expression in patient derived explants and individuals with tumours containing a small fraction of these cells had greatly improved progression-free survival compared to those in the highest quartile for expression. The use of curcumin to minimise this cellular population may yield significant benefit and its clinical evaluation is warranted. Overall, this study provides crucial mechanistic insight, identifying patient populations likely to benefit from curcumin for prevention of sporadic CRC and theragnostic biomarkers for assessing efficacy.</div></div>","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":"629 ","pages":"Article 217885"},"PeriodicalIF":9.1,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144339913","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Global Cancer Burden Forecast for 204 Countries and Territories, 2022–2050: A Predictive Analysis from the Global Burden of Disease Study 2021","authors":"Jinghao Liang ,&nbsp;Yijian Lin ,&nbsp;Wenxi Wang ,&nbsp;Jingchun Ni ,&nbsp;Hongmiao Lin ,&nbsp;Zishan Huang ,&nbsp;Jihao Qi ,&nbsp;Zhaofeng Tan ,&nbsp;Hengrui Liang ,&nbsp;Jianxing He","doi":"10.1016/j.canlet.2025.217883","DOIUrl":"10.1016/j.canlet.2025.217883","url":null,"abstract":"","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":"629 ","pages":"Article 217883"},"PeriodicalIF":9.1,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144339914","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A novel mismatch repair deficient lung adenocarcinoma model for immunotherapy research","authors":"Ivan Zadra ,&nbsp;Etna Abad ,&nbsp;Anastasia Krasko ,&nbsp;Víctor Cerdán Porqueras ,&nbsp;Marc Subirana-Granés,&nbsp;Diana Reyes,&nbsp;Pablo Borredat,&nbsp;Lorenzo Pasquali,&nbsp;Jose Aramburu ,&nbsp;Cristina López-Rodríguez ,&nbsp;Ana Janic","doi":"10.1016/j.canlet.2025.217882","DOIUrl":"10.1016/j.canlet.2025.217882","url":null,"abstract":"<div><div>Immunotherapy has revolutionised cancer treatment, yet responses vary significantly based on tumour characteristics and microenvironment. Here, we developed and analysed subcutaneous and orthotopic immunocompetent mice models of mismatch repair-deficient (dMMR) lung adenocarcinoma (LUAD) by selectively ablating Mlh1. Subcutaneous tumours demonstrated partial sensitivity to anti-PD-1 therapy, whereas orthotopic tumours exhibited robust responses, with substantial reductions in tumour burden. Although both models displayed to some extent a robust immune microenvironment, they differed in immune cell infiltration patterns following anti-PD-1 treatment, underscoring the critical influence of anatomical site and tumour context in shaping immunotherapy outcomes. Furthermore, the use of clonal cell lines with enriched neoantigen frequency in the orthotopic model highlighted the role of clonal heterogeneity in modulating therapeutic efficacy. Together, our findings emphasise the relevance of orthotopic models for preclinical evaluation and suggest that they more accurately reflect clinical responses to immune checkpoint blockade in dMMR LUAD.</div></div>","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":"629 ","pages":"Article 217882"},"PeriodicalIF":9.1,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144366410","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Liver metastasis or peritoneal metastasis: single-cell RNA sequencing reveals the organotropism in colorectal cancer is driven by distinct partial-EMT processes","authors":"Chengxuan Yu ,&nbsp;Wei Lu ,&nbsp;Junqing Wu ,&nbsp;Xing Fang ,&nbsp;Xinru Wang ,&nbsp;Guodong Zhang ,&nbsp;Sheng Chen ,&nbsp;Yuqing Mei ,&nbsp;Haide Chen ,&nbsp;Fang Ye ,&nbsp;Hang Yang ,&nbsp;Yucheng Qian ,&nbsp;Xiangxing Kong ,&nbsp;Peijing Zhang ,&nbsp;Jingjing Wang ,&nbsp;Guoji Guo ,&nbsp;Kefeng Ding","doi":"10.1016/j.canlet.2025.217880","DOIUrl":"10.1016/j.canlet.2025.217880","url":null,"abstract":"<div><div>Liver and peritoneum are the most common metastatic organs in colorectal cancer. However, the mechanisms of metastatic organotropism remain unexplored. Here we used single-cell RNA-sequencing to reveal the intermediate EMT state of tumor cells from colorectal cancer liver metastasis (CRLM) and colorectal cancer peritoneum metastasis (CRPM). There was a significant heterogeneity in expression profiles across multiple cell types in the tumor microenvironment between two groups. Although both groups of tumor cells obtained the activation of EMT, they were in different partial-EMT (pEMT) states and expressed distinct pEMT markers. Tumor cells in CRLM group were more in an epithelial-biased pEMT state, while a higher proportion of cells in CRPM group was in a mesenchymal-biased pEMT state. In addition, we observed differentially infiltrated myeloid and fibroblast sub-clusters, rendering the peritoneal metastasis group a more prominent inflammatory stimulus. Our study provides a comprehensive resource at single-cell level for in-depth exploration of metastatic organotropism in CRC.</div></div>","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":"629 ","pages":"Article 217880"},"PeriodicalIF":9.1,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144331075","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CircSRPK1 mediated by the exon junction complex promotes gastric cancer progression by interacting with hnRNP A2B1 to regulate RON mRNA alternative splicing","authors":"Shanshan Yu ,&nbsp;Ming Chen ,&nbsp;Kecheng Jiang ,&nbsp;Cheng Chen ,&nbsp;Jinxiao Liang ,&nbsp;Jingjing Zheng ,&nbsp;Bin Lou ,&nbsp;Jun Lu ,&nbsp;Xiaohua Zhu ,&nbsp;Donghui Zhou","doi":"10.1016/j.canlet.2025.217879","DOIUrl":"10.1016/j.canlet.2025.217879","url":null,"abstract":"<div><div>Gastric cancer (GC) is one of the most common malignant tumors with high heterogeneity, and its etiology and pathogenesis are unclear. Recently, many aberrantly alternatively spliced isoforms of the receptor tyrosine kinase recepteur d'origine nantais (RON) have been shown to play vital roles in GC development. Serine/arginine protein kinase 1 (SRPK1) is widely recognized as a key splicing factor kinase that regulates various steps of alternative splicing. Recent studies on SRPK1 have focused mainly on splicing activity, but the role of SRPK1-derived circular RNAs in RON alternative splicing and GC progression is unknown. Among all SRPK1-derived circRNAs in the CircInteractome, hsa_circ_0076168 (henceforth called circSRPK1) was upregulated in GC tissues compared with adjacent normal tissues, which was often associated with adverse outcomes in GC patients. Functionally, circSRPK1 promoted the malignant phenotype of GC. Mechanistically, circSRPK1 directly interacted with heterogeneous nuclear ribonucleoprotein A2B1 (hnRNP A2B1) to promote its nuclear translocation and binding to the exonic splicing enhancer (ESE) element on RON mRNA; this regulated the alternative splicing of downstream RON mRNA, induced RONΔ160 production, and ultimately promoted GC progression. More importantly, circSRPK1 production in GC cells was regulated by a component of the exon junction complex MAGOH, which enhanced the binding of EIF4A3 to the circSRPK1 transcript. Additionally, MAGOH knockdown rescued circSRPK1-mediated RONΔ160 formation and GC malignancy. Overall, our research revealed a novel mechanism by which the MAGOH–circSRPK1–hnRNPA2B1–RONΔ160 axis regulated GC cell proliferation and metastasis, broadening the current understanding of circRNA-mediated regulation of tumor progression through aberrant alternative splicing.</div></div>","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":"629 ","pages":"Article 217879"},"PeriodicalIF":9.1,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144307254","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting the cholinergic-astrocyte axis: A novel strategy for brain metastasis prevention in lung adenocarcinoma","authors":"Xiangze Li ,&nbsp;Kun Liu ,&nbsp;Ziyao Zhang ,&nbsp;Wangyang Zhu ,&nbsp;Miao Zhao ,&nbsp;Dan Zhao ,&nbsp;Yue Zhao ,&nbsp;Yang Zhang ,&nbsp;Fangqiu Fu ,&nbsp;Haiquan Chen","doi":"10.1016/j.canlet.2025.217870","DOIUrl":"10.1016/j.canlet.2025.217870","url":null,"abstract":"<div><div>Brain metastasis (BM) represents a highly detrimental complication of lung adenocarcinoma (LUAD), persisting even following curative resection of primary tumors, with limited effective preventive measures. This study explores the role of cholinergic metabolism, a pathway crucial for both LUAD progression and brain function, in the pathogenesis of BM. Through comprehensive analysis of RNA-sequencing data from 875 LUAD cases and validation using tissue microarrays from 280 patients, we identified cholinergic metabolic activation as a defining characteristic of tumors prone to BM, which is significantly associated with poor survival outcomes. Mechanistic investigations revealed that acetylcholinesterase (AChE) facilitates BM via dual pro-metastatic mechanisms: immunosuppression and disruption of the blood-brain barrier (BBB). Specifically, AChE-induced overactivation of cholinergic receptors triggers excessive Ca²⁺ influx, leading to ATP release and astrocyte apoptosis, thereby promoting tumor extravasation across the BBB. Furthermore, choline acetyltransferase enhances tumor aggressiveness by stimulating proliferation and migration. Single-cell RNA sequencing of 26 BM sites and 8 normal brain samples, corroborated by <em>in vitro</em> experiments, elucidated tumor-mediated alterations in the BBB and immune cells. Notably, pharmacological intervention with the AChE inhibitor donepezil exhibited substantial efficacy in preventing BM. Collectively, these findings uncover a targetable cholinergic metabolism-astrocyte axis governing BM organotropism, providing a transformative strategy to intercept metastatic progression in LUAD.</div></div>","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":"628 ","pages":"Article 217870"},"PeriodicalIF":9.1,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144290836","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}