Molecular Oncology最新文献

{"title":"Multidimensional OMICs reveal ARID1A orchestrated control of DNA damage, splicing, and cell cycle in normal-like and malignant urothelial cells.","authors":"Rebecca M Schlösser, Florian Krumbach, Eyleen Corrales, Geoffroy Andrieux, Christian Preisinger, Franziska Liss, Alexandra Golzmann, Melanie Boerries, Kerstin Becker, Ruth Knüchel, Stefan Garczyk, Bernhard Lüscher","doi":"10.1002/1878-0261.70019","DOIUrl":"https://doi.org/10.1002/1878-0261.70019","url":null,"abstract":"<p><p>Epigenetic regulators, such as the SWI/SNF complex, with important roles in tissue development and homeostasis, are frequently mutated in cancer. ARID1A, a subunit of the SWI/SNF complex, is mutated in approximately 20% of all bladder tumors; however, the consequences of this remain poorly understood. Finding truncations to be the most common mutation, we generated loss- and gain-of-function models to conduct RNA-Seq, interactome analyses, Omni-ATAC-Seq, and functional studies to characterize ARID1A-affected pathways potentially suitable for the treatment of ARID1A-deficient bladder cancers. We observed decreased cell proliferation and deregulation of stress-regulated pathways, including DNA repair, in ARID1A-deficient cells. Furthermore, ARID1A was linked to alternative splicing and translational regulation on RNA and interactome levels. ARID1A deficiency drastically reduced the accessibility of chromatin, especially around introns and distal enhancers, in a functional enrichment analysis. Less accessible chromatin areas were mapped to pathways such as cell proliferation and DNA damage response. Indeed, the G2/M checkpoint appeared impaired after DNA damage in ARID1A-deficient cells. Together, our data highlight the broad impact of ARID1A loss and the possibility of targeting proliferative and DNA repair pathways for treatment.</p>","PeriodicalId":18764,"journal":{"name":"Molecular Oncology","volume":" ","pages":""},"PeriodicalIF":6.6,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143764461","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrative transcriptomic analysis identifies emetine as a promising candidate for overcoming acquired resistance to ALK inhibitors in lung cancer.","authors":"Sang-Min Park, Keeok Haam, Haejeong Heo, Doyeong Kim, Min-Ju Kim, Hyo-Jung Jung, Seongwon Cha, Mirang Kim, Haeseung Lee","doi":"10.1002/1878-0261.13738","DOIUrl":"10.1002/1878-0261.13738","url":null,"abstract":"<p><p>Anaplastic lymphoma kinase (ALK; also known as ALK tyrosine kinase receptor) inhibitors (ALKi) are effective in treating lung cancer patients with chromosomal rearrangement of ALK. However, continuous treatment with ALKis invariably leads to acquired resistance in cancer cells. In this study, we propose an efficient strategy to suppress ALKi resistance through a meta-analysis of transcriptome data from various cell models of acquired resistance to ALKis. We systematically identified gene signatures that consistently showed altered expression during the development of resistance and conducted computational drug screening using these signatures. We identified emetine as a promising candidate compound to inhibit the growth of ALKi-resistant cells. We demonstrated that emetine exhibited effectiveness in inhibiting the growth of ALKi-resistant cells, and further interpreted its impact on the resistant signatures through drug-induced RNA-sequencing data. Our transcriptome-guided systematic approach paves the way for efficient drug discovery to overcome acquired resistance to cancer therapy.</p>","PeriodicalId":18764,"journal":{"name":"Molecular Oncology","volume":" ","pages":"1155-1169"},"PeriodicalIF":6.6,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11977641/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142623929","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}

{"title":"Unraveling the metastasis-preventing effect of miR-200c in vitro and in vivo.","authors":"Bianca Köhler, Emily Brieger, Tom Brandstätter, Elisa Hörterer, Ulrich Wilk, Jana Pöhmerer, Anna Jötten, Philipp Paulitschke, Chase P Broedersz, Stefan Zahler, Joachim O Rädler, Ernst Wagner, Andreas Roidl","doi":"10.1002/1878-0261.13712","DOIUrl":"10.1002/1878-0261.13712","url":null,"abstract":"<p><p>Advanced breast cancer, as well as ineffective treatments leading to surviving cancer cells, can result in the dissemination of these malignant cells from the primary tumor to distant organs. Recent research has shown that microRNA 200c (miR-200c) can hamper certain steps of the invasion-metastasis cascade. However, it is still unclear whether miR-200c expression alone is sufficient to prevent breast cancer cells from metastasis formation. Hence, we performed a xenograft mouse experiment with inducible miR-200c expression in MDA-MB 231 cells. The ex vivo analysis of metastatic sites in a multitude of organs, including lung, liver, brain, and spleen, revealed a dramatically reduced metastatic burden in mice with miR-200c-expressing tumors. A fundamental prerequisite for metastasis formation is the motility of cancer cells and, therefore, their migration. Consequently, we analyzed the effect of miR-200c on collective- and single-cell migration in vitro, utilizing MDA-MB 231 and MCF7 cell systems with genetically modified miR-200c expression. Analysis of collective-cell migration revealed confluence-dependent motility of cells with altered miR-200c expression. Additionally, scratch assays showed an enhanced predisposition of miR-200c-negative cells to leave cell clusters. The in-between stage of collective- and single-cell migration was validated using transwell assays, which showed reduced migration of miR-200c-positive cells. Finally, to measure migration at the single-cell level, a novel assay on dumbbell-shaped micropatterns was performed, which revealed that miR-200c critically determines confined cell motility. All of these results demonstrate that sole expression of miR-200c impedes metastasis formation in vivo and migration in vitro and highlights miR-200c as a metastasis suppressor in breast cancer.</p>","PeriodicalId":18764,"journal":{"name":"Molecular Oncology","volume":" ","pages":"1029-1053"},"PeriodicalIF":6.6,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11977663/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142470171","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}

{"title":"CRISPR targeting of FOXL2 c.402C>G mutation reduces malignant phenotype in granulosa tumor cells and identifies anti-tumoral compounds.","authors":"Sandra Amarilla-Quintana, Paloma Navarro, Iván Hernández, Alejandra Ramos, Ana Montero-Calle, Pablo Cabezas-Sainz, Maria J Barrero, Diego Megías, Borja Vilaplana-Martí, Carolina Epifano, Déborah Gómez-Dominguez, Sara Monzón, Isabel Cuesta, Laura Sánchez, Rodrigo Barderas, Jesús García-Donas, Alberto Martín, Ignacio Pérez de Castro","doi":"10.1002/1878-0261.13799","DOIUrl":"10.1002/1878-0261.13799","url":null,"abstract":"<p><p>Forkhead box L2 (FOXL2) encodes a transcription factor essential for sex determination, and ovary development and maintenance. Mutations in this gene are implicated in syndromes involving premature ovarian failure and granulosa cell tumors (GCTs). This rare cancer accounts for less than 5% of diagnosed ovarian cancers and is causally associated with the FOXL2 c.402C>G, p.C134W mutation in 97% of the adult cases (AGCTs). In this study, we employed CRISPR technology to specifically eliminate the FOXL2 c.402C>G mutation in granulosa tumor cells. Our results show that this Cas9-mediated strategy selectively targets the mutation without affecting the wild-type allele. Granulosa cells lacking FOXL2 c.402C>G exhibit a reduced malignant phenotype, with significant changes in cell proliferation and invasion. Furthermore, these modified cells are more susceptible to dasatinib and ketoconazole. Transcriptomic and proteomic analyses reveal that CRISPR-modified granulosa tumor cells shift their expression profiles towards a wild-type-like phenotype. Additionally, this altered expression signature has led to the identification of new compounds with antiproliferative and pro-apoptotic effects on granulosa tumor cells. Our findings demonstrate the potential of CRISPR technology for the specific targeting and elimination of a mutation causing GCTs, highlighting its therapeutic promise for treating this rare ovarian cancer.</p>","PeriodicalId":18764,"journal":{"name":"Molecular Oncology","volume":" ","pages":"1092-1116"},"PeriodicalIF":6.6,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11977662/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142951890","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}

{"title":"SKA1 promotes oncogenic properties in oral dysplasia and oral squamous cell carcinoma, and augments resistance to radiotherapy.","authors":"Alexander Michael Grandits, Barbara Andrea Reinoehl, Renate Wagner, Peter Kuess, Franziska Eckert, Anna Sophie Berghoff, Thorsten Fuereder, Rotraud Wieser","doi":"10.1002/1878-0261.13780","DOIUrl":"10.1002/1878-0261.13780","url":null,"abstract":"<p><p>Oral squamous cell carcinoma (OSCC) is a malignancy associated with high morbidity and mortality, yet treatment options are limited. In addition to genetic alterations, aberrant gene expression contributes to the pathology of malignant diseases. In the present study, we identified 629 genes consistently dysregulated between OSCC and normal oral mucosa across nine public gene expression datasets. Among them, mitosis-related genes were significantly enriched, including spindle and kinetochore-associated complex subunit 1 (SKA1), whose roles in OSCC had been studied only to a very limited extent. We show that SKA1 promoted proliferation and colony formation in 2D and 3D, shortened the duration of metaphase, and increased the migration of OSCC cell lines. In addition, high SKA1 expression enhanced radioresistance, a previously unknown effect of this gene, which was accompanied by a reduction of radiation-induced senescence. SKA1 was also upregulated in a subset of advanced oral premalignancies and promoted tumor-relevant properties in a corresponding cell line. Gene expression patterns evoked by SKA1 overexpression confirmed that this gene is able to advance properties required for both early and advanced stages of tumorigenesis. In summary, our data show that SKA1 contributes to malignant progression in OSCC and may be a useful marker of radioresistance in this disease.</p>","PeriodicalId":18764,"journal":{"name":"Molecular Oncology","volume":" ","pages":"1054-1074"},"PeriodicalIF":6.6,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11977640/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142829427","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}

{"title":"Hijacking the BAF complex: the mechanistic interplay of ARID1A and EWS::FLI1 in Ewing sarcoma.","authors":"Erich J Sohn, David S Libich","doi":"10.1002/1878-0261.13742","DOIUrl":"10.1002/1878-0261.13742","url":null,"abstract":"<p><p>Ewing sarcoma, an aggressive pediatric cancer, is driven by the EWS::FLI1 fusion protein, which disrupts gene expression by hijacking the BAF chromatin remodeling complex. Central to this mechanism is the formation of biomolecular condensates, mediated by the prion-like domains (PrLDs) of EWS and ARID1A, a core BAF subunit. ARID1A serves as a critical interface between EWS::FLI1 and the BAF complex, with its condensate-forming ability essential for the aberrant gene expression that drives tumor growth. The loss of condensate-competent ARID1A significantly impairs tumor progression, identifying it as a potential therapeutic target. However, targeting condensate formation is challenging due to the transient nature of the interactions involved, complicating the development of effective inhibitors. This work underscores the importance of further investigation into therapeutic strategies aimed at disrupting condensate formation in Ewing sarcoma and other related malignancies.</p>","PeriodicalId":18764,"journal":{"name":"Molecular Oncology","volume":" ","pages":"961-964"},"PeriodicalIF":6.6,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11977654/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142350335","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}

{"title":"Decoding multicellular interaction networks-a new horizon in tumor microenvironment research.","authors":"Roi Balaban, Merav Cohen","doi":"10.1002/1878-0261.13810","DOIUrl":"10.1002/1878-0261.13810","url":null,"abstract":"<p><p>The tumor microenvironment (TME) milieu directs a plethora of tumor-modulating functions. Recent years have seen pivotal breakthroughs in our understanding of the TME's role in tumor initiation and progression, with tangible clinical applications. Individual components of the TME exert their function predominantly by cell-cell crosstalk, both in the form of physical interaction and secreted factors. Notably, different spatial niches represent exclusive signaling hubs in the TME, propagating pro- or antitumoral functions. The exploration of these interactions has been vastly facilitated by novel molecular technologies, each of which provides a different perspective on this intricate intercellular communication network. Together, these complementary methods paint a detailed, high-resolution map of the TME's interaction landscape. In this viewpoint, we explore how cellular interactions can unlock a new level of understanding of TME complexity, and discuss the promises and challenges of characterizing tumors based on their cellular interaction footprint.</p>","PeriodicalId":18764,"journal":{"name":"Molecular Oncology","volume":" ","pages":"957-960"},"PeriodicalIF":6.6,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11977648/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143189841","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}

{"title":"ShcD adaptor protein drives invasion of triple negative breast cancer cells by aberrant activation of EGFR signaling.","authors":"Hayley R Lau, Hayley S Smith, Begüm Alural, Claire E Martin, Laura A New, Manali Tilak, Sara L Banerjee, Hannah N Robeson, Nicolas Bisson, Anne-Claude Gingras, Jasmin Lalonde, Nina Jones","doi":"10.1002/1878-0261.70022","DOIUrl":"https://doi.org/10.1002/1878-0261.70022","url":null,"abstract":"<p><p>Triple-negative breast cancer (TNBC) is highly metastatic and presents clinical challenges given the lack of targeted therapies. Here, we report that the ShcD phosphotyrosine adaptor protein is upregulated in TNBC, and its expression correlates with overall reduced patient survival and decreased response to chemotherapy. In human breast cancer cells, we demonstrate that ShcD expression promotes cell invasion and reduces adhesion, and that these effects are abrogated by mutating the ShcD phosphotyrosine binding (PTB) domain. Similarly, in a three-dimensional assembloid model, ShcD-expressing spheroids derived from brain metastatic TNBC cells show enhanced infiltration into cerebral organoids. Using a proteomic screen for ShcD binding partners, we identify multiple components of epidermal growth factor receptor (EGFR) signaling and confirm these interactions with ShcD but not the PTB mutant. Interestingly, the ShcD interactome correlates with EGFR tyrosine kinase inhibitor resistance, in line with our findings that ShcD overexpression results in hyperphosphorylation of EGFR while ShcD knockout or PTB mutation reverts this response. Lastly, pharmacological inhibition of the ShcD PTB domain using indomethacin in TNBC cells decreases EGFR binding and hyperphosphorylation and reduces cell invasion. Altogether, our results identify ShcD as a potential contributor to metastasis in TNBC, and they provide a molecular basis for clinical targeting of adaptor proteins.</p>","PeriodicalId":18764,"journal":{"name":"Molecular Oncology","volume":" ","pages":""},"PeriodicalIF":6.6,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143730501","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting the AKT/mTOR pathway attenuates the metastatic potential of colorectal carcinoma circulating tumor cells in a murine xenotransplantation model.","authors":"Daniel J Smit, Thais Pereira-Veiga, Helena Brauer, Michael Horn, Paula Nissen, Thomas Mair, Bente Siebels, Hannah Voß, Ruimeng Zhuang, Marie-Therese Haider, Desiree Loreth, Margarita Iskhakova, Bele Lindemann, Julian Kött, Laure Cayrefourcq, Jasmin Wellbrock, Hartmut Schlüter, Klaus Pantel, Catherine Alix-Panabières, Manfred Jücker","doi":"10.1002/1878-0261.70024","DOIUrl":"https://doi.org/10.1002/1878-0261.70024","url":null,"abstract":"<p><p>Circulating tumor cells (CTCs) play an important role in metastasis formation. Aberrant signaling of oncogenic pathways (e.g., PI3K/AKT/mTOR pathway) drives tumor progression. In this work, the susceptibility of the colon cancer CTC-derived cell line CTC-MCC-41 to AKT and mammalian target of rapamycin (mTOR) inhibitors was evaluated. Additionally, the functional role of the expressed AKT isoforms was characterized in this cell line. The efficacy of the AKT inhibitor MK2206, the mTOR inhibitor RAD001, and the combination was examined in CTC-MCC-41 cells in a murine intracardiac xenotransplantation model. Furthermore, stable isoform-specific AKT1 or AKT2 knockdowns (KDs) as well as AKT1/AKT2 double-KD cells were generated. Differentially regulated proteins and phospho-peptides were identified using liquid chromatography coupled mass spectrometry (LC-MS). CTC-MCC-41 cells showed a high susceptibility for dual targeting of AKT and mTOR in vivo, indicating that selective eradication of CTCs by AKT/mTOR inhibitors may be considered a new treatment option in cancer. KD of AKT1 or AKT2 significantly reduced the proliferation of CTC-MCC-41 cells. AKT KDs share commonly regulated proteins and phospho-proteins, but also regulate a large number uniquely. AKT1/AKT2 double-KD cells show a strongly dysregulated replication machinery, as well as a decrease in cell cycle activity and stem-cell-associated processes, underlining the non-redundant role of AKT isoforms.</p>","PeriodicalId":18764,"journal":{"name":"Molecular Oncology","volume":" ","pages":""},"PeriodicalIF":6.6,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143701066","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tonic signaling of the B-cell antigen-specific receptor is a common functional hallmark in chronic lymphocytic leukemia cell phosphoproteomes at early disease stages.","authors":"Paula Díez, Pablo Juanes-Velasco, Marina L García-Vaquero, Conrad Droste, Alicia Landeira-Viñuela, Miguel Alcoceba, Helena Fidalgo-Gómez, Sara Misiego-Herrero, Almudena Navarro-Bailón, Mónica Baile, José M Bastida, Jose Manuel Sanchez-Santos, Rafael Góngora, Julia Almeida, Marcos Gonzalez-Diaz, Alberto Orfao, Javier De Las Rivas, Manuel Fuentes","doi":"10.1002/1878-0261.70032","DOIUrl":"https://doi.org/10.1002/1878-0261.70032","url":null,"abstract":"<p><p>B-cell chronic lymphocytic leukemia (B-CLL) is characterized by highly heterogeneous genomic alterations and altered signaling pathways, with limited studies on its proteome. Our study presents a comprehensive analysis of the proteome and phosphoproteome in B-CLL and CLL-like monoclonal B-cell lymphocytosis (MBL) primary cells. Using high-resolution mass spectrometry, we identified 2970 proteins and 316 phosphoproteins across five tumor samples, including 55 newly identified phosphopeptides (ProteomeXchange-PXD005997). Our multifaceted approach also integrated protein microarrays and western blotting for further data validation in a new patient cohort of 14 patients. Despite sharing 73% of their proteomes, the phosphoproteomes varied significantly among samples, independent of cytogenetic alterations and immunoglobulin heavy variable cluster (IGHV) mutational status. We identified common functional hallmarks in B-CLL and MBL phosphoproteomes, notably tonic signaling (low-level, constitutive signaling) of the B-cell antigen-specific receptor (BCR) and nuclear factor NF-kappa-B (NF-kβ)/signal transducer and activator of transcription 3 (STAT3) pathways. Nine phosphoproteins involved in BCR signaling were further validated, showing a high correlation with early disease stages. Our study advances the field by providing a detailed perspective on the proteome and phosphoproteome of B-CLL cells, revealing signaling pathways crucial for disease development and progression. Integrating diverse proteomics techniques and identifying novel phosphopeptides offers new insights into CLL biology, potentially informing future therapeutic strategies and biomarker development for early diagnosis and personalized treatment.</p>","PeriodicalId":18764,"journal":{"name":"Molecular Oncology","volume":" ","pages":""},"PeriodicalIF":6.6,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143701067","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}