Cancer discovery最新文献

{"title":"Clinical Validation of a Cell-Free DNA Fragmentome Assay for Augmentation of Lung Cancer Early Detection.","authors":"Peter J Mazzone, Peter B Bach, Jacob Carey, Caitlin A Schonewolf, Katalin Bognar, Manmeet S Ahluwalia, Marcia Cruz-Correa, David Gierada, Sonali Kotagiri, Kathryn Lloyd, Fabien Maldonado, Jesse D Ortendahl, Lecia V Sequist, Gerard A Silvestri, Nichole Tanner, Jeffrey C Thompson, Anil Vachani, Kwok-Kin Wong, Ali H Zaidi, Joseph Catallini, Ariel Gershman, Keith Lumbard, Laurel K Millberg, Jeff Nawrocki, Carter Portwood, Aakanksha Rangnekar, Carolina Campos Sheridan, Niti Trivedi, Tony Wu, Yuhua Zong, Lindsey Cotton, Allison Ryan, Christopher Cisar, Alessandro Leal, Nicholas Dracopoli, Robert B Scharpf, Victor E Velculescu, Luke R G Pike","doi":"10.1158/2159-8290.CD-24-0519","DOIUrl":"10.1158/2159-8290.CD-24-0519","url":null,"abstract":"<p><p>Lung cancer screening via annual low-dose computed tomography has poor adoption. We conducted a prospective case-control study among 958 individuals eligible for lung cancer screening to develop a blood-based lung cancer detection test that when positive is followed by a low-dose computed tomography. Changes in genome-wide cell-free DNA fragmentation profiles (fragmentomes) in peripheral blood reflected genomic and chromatin characteristics of lung cancer. We applied machine learning to fragmentome features to identify individuals who were more or less likely to have lung cancer. We trained the classifier using 576 cases and controls from study samples and validated it in a held-out group of 382 cases and controls. The validation demonstrated high sensitivity for lung cancer and consistency across demographic groups and comorbid conditions. Applying test performance to the screening eligible population in a 5-year model with modest utilization assumptions suggested the potential to prevent thousands of lung cancer deaths. Significance: Lung cancer screening has poor adoption. Our study describes the development and validation of a novel blood-based lung cancer screening test utilizing a highly affordable, low-coverage genome-wide sequencing platform to analyze cell-free DNA fragmentation patterns. The test could improve lung cancer screening rates leading to substantial public health benefits. See related commentary by Haber and Skates, p. 2025.</p>","PeriodicalId":9430,"journal":{"name":"Cancer discovery","volume":" ","pages":"2224-2242"},"PeriodicalIF":29.7,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11528203/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141199173","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Redefining the Gastric Microbes in Promoting Gastric Tumorigenesis: The Rise of the Non-H. pylori Microbiome.","authors":"Chi Chun Wong, Jun Yu","doi":"10.1158/2159-8290.CD-24-0835","DOIUrl":"10.1158/2159-8290.CD-24-0835","url":null,"abstract":"<p><p>Gastric cancer remains one of the top cancers in China compared with Western countries, mainly attributed to the high rates of Helicobacter pylori infection. However, recent discoveries on the non-H. pylori gastric microbiome have led to a paradigm shift in our understanding of microbial risk factors driving gastric cancer, which will impact future screening and prevention strategies.</p>","PeriodicalId":9430,"journal":{"name":"Cancer discovery","volume":"14 11","pages":"2051-2054"},"PeriodicalIF":29.7,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142557242","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 of Resistance to Oncogenic KRAS Inhibition in Pancreatic Cancer.","authors":"Julien Dilly, Megan T Hoffman, Laleh Abbassi, Ziyue Li, Francesca Paradiso, Brendan D Parent, Connor J Hennessey, Alexander C Jordan, Micaela Morgado, Shatavisha Dasgupta, Giselle A Uribe, Annan Yang, Kevin S Kapner, Felix P Hambitzer, Li Qiang, Hanrong Feng, Jacob Geisberg, Junning Wang, Kyle E Evans, Hengyu Lyu, Aislyn Schalck, Ningping Feng, Anastasia M Lopez, Christopher A Bristow, Michael P Kim, Kimal I Rajapakshe, Vahid Bahrambeigi, Jennifer A Roth, Kavita Garg, Paola A Guerrero, Ben Z Stanger, Simona Cristea, Scott W Lowe, Timour Baslan, Eliezer M Van Allen, Joseph D Mancias, Emily Chan, Abraham Anderson, Yuliya V Katlinskaya, Alex K Shalek, David S Hong, Shubham Pant, Jill Hallin, Kenna Anderes, Peter Olson, Timothy P Heffernan, Seema Chugh, James G Christensen, Anirban Maitra, Brian M Wolpin, Srivatsan Raghavan, Jonathan A Nowak, Peter S Winter, Stephanie K Dougan, Andrew J Aguirre","doi":"10.1158/2159-8290.CD-24-0177","DOIUrl":"10.1158/2159-8290.CD-24-0177","url":null,"abstract":"<p><p>KRAS inhibitors demonstrate clinical efficacy in pancreatic ductal adenocarcinoma (PDAC); however, resistance is common. Among patients with KRASG12C-mutant PDAC treated with adagrasib or sotorasib, mutations in PIK3CA and KRAS, and amplifications of KRASG12C, MYC, MET, EGFR, and CDK6 emerged at acquired resistance. In PDAC cell lines and organoid models treated with the KRASG12D inhibitor MRTX1133, epithelial-to-mesenchymal transition and PI3K-AKT-mTOR signaling associate with resistance to therapy. MRTX1133 treatment of the KrasLSL-G12D/+; Trp53LSL-R172H/+; p48-Cre (KPC) mouse model yielded deep tumor regressions, but drug resistance ultimately emerged, accompanied by amplifications of Kras, Yap1, Myc, Cdk6, and Abcb1a/b, and co-evolution of drug-resistant transcriptional programs. Moreover, in KPC and PDX models, mesenchymal and basal-like cell states displayed increased response to KRAS inhibition compared to the classical state. Combination treatment with KRASG12D inhibition and chemotherapy significantly improved tumor control in PDAC mouse models. Collectively, these data elucidate co-evolving resistance mechanisms to KRAS inhibition and support multiple combination therapy strategies. Significance: Acquired resistance may limit the impact of KRAS inhibition in patients with PDAC. Using clinical samples and multiple preclinical models, we define heterogeneous genetic and non-genetic mechanisms of resistance to KRAS inhibition that may guide combination therapy approaches to improve the efficacy and durability of these promising therapies for patients. See related commentary by Marasco and Misale, p. 2018.</p>","PeriodicalId":9430,"journal":{"name":"Cancer discovery","volume":" ","pages":"2135-2161"},"PeriodicalIF":29.7,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11528210/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141554212","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immunogenicity and Efficacy of Personalized Adjuvant mRNA Cancer Vaccines.","authors":"Pedro Berraondo, Raquel Cuesta, Miguel F Sanmamed, Ignacio Melero","doi":"10.1158/2159-8290.CD-24-1196","DOIUrl":"10.1158/2159-8290.CD-24-1196","url":null,"abstract":"<p><p>In this issue, Gainor and colleagues report on the immunogenicity of personalized neoantigen-encoding mRNA vaccines that elicit measurable polyfunctional CD8+ and CD4+ T-cell responses in patients whose tumors have been resected. Reactivity is substantiated to 20% to 30% of the predicted MHC-I and MHC-II epitopes in four patients with NSCLC postsurgically treated with the vaccine alone and in 12 patients with melanoma treated with their individualized vaccines plus pembrolizumab in the context of a phase 1 clinical trial (NCT03313778). See related article by Gainor et al., p. 2209.</p>","PeriodicalId":9430,"journal":{"name":"Cancer discovery","volume":"14 11","pages":"2021-2024"},"PeriodicalIF":29.7,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142557241","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":"ROR2 Regulates Cellular Plasticity in Pancreatic Neoplasia and Adenocarcinoma.","authors":"Simone Benitz, Alec Steep, Malak M Nasser, Jonathan Preall, Ujjwal Mukund Mahajan, Holly McQuithey, Ian Loveless, Erick T Davis, Hui-Ju Wen, Daniel W Long, Thomas Metzler, Samuel Zwernik, Michaela Louw, Donald Rempinski, Daniel J Salas-Escabillas, Sydney M Brender, Linghao Song, Ling Huang, Brian K Theisen, Zhenyu Zhang, Nina G Steele, Ivonne Regel, Filip Bednar, Howard C Crawford","doi":"10.1158/2159-8290.CD-24-0137","DOIUrl":"10.1158/2159-8290.CD-24-0137","url":null,"abstract":"<p><p>Cellular plasticity is a hallmark of pancreatic ductal adenocarcinoma (PDAC) starting from the conversion of normal cells into precancerous lesions, to the progression of carcinoma subtypes associated with aggressiveness and therapeutic response. We discovered that normal acinar cell differentiation, maintained by the transcription factor PDX1, suppresses a broad gastric cell identity that is maintained in metaplasia, neoplasia, and the classical subtype of PDAC in a mouse and human. We identified the receptor tyrosine kinase ROR2 as marker of a gastric metaplasia-like identity in pancreas neoplasms. Ablation of Ror2 in a mouse model of pancreatic tumorigenesis promoted a switch to a gastric pit cell identity that largely persisted through progression to the classical subtype of PDAC. In both human and mouse pancreatic cancer, ROR2 activity continued to antagonize the gastric pit cell identity, strongly promoting an epithelial to mesenchymal transition, conferring resistance to KRAS inhibition, and vulnerability to AKT inhibition. Significance: We discovered the receptor tyrosine kinase ROR2 as an important regulator of cellular identity in pancreatic precancerous lesions and pancreatic cancer. ROR2 drives an aggressive PDAC phenotype and confers resistance to KRAS inhibitors, suggesting that targeting ROR2 will enhance sensitivity to this new generation of targeted therapies. See related commentary by Marasco and Misale, p. 2018.</p>","PeriodicalId":9430,"journal":{"name":"Cancer discovery","volume":" ","pages":"2162-2182"},"PeriodicalIF":29.7,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11528200/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141554214","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"T-cell Responses to Individualized Neoantigen Therapy mRNA-4157 (V940) Alone or in Combination with Pembrolizumab in the Phase 1 KEYNOTE-603 Study.","authors":"Justin F Gainor, Manish R Patel, Jeffrey S Weber, Martin Gutierrez, Julie E Bauman, Jeffrey M Clarke, Ricklie Julian, Aaron J Scott, Jessica L Geiger, Kedar Kirtane, Celine Robert-Tissot, Brandon Coder, Moomal Tasneem, Jing Sun, Wei Zheng, Lauren Gerbereux, Andressa Laino, Filippos Porichis, Jack Russella Pollard, Peijie Hou, Vasudha Sehgal, Xing Chen, Manju Morrissey, Hikmat N Daghestani, Igor Feldman, Lakshmi Srinivasan, Joshua P Frederick, Michelle Brown, Praveen Aanur, Robert Meehan, Howard A Burris","doi":"10.1158/2159-8290.CD-24-0158","DOIUrl":"10.1158/2159-8290.CD-24-0158","url":null,"abstract":"<p><p>mRNA-4157 (V940) is an individualized neoantigen therapy targeting up to 34 patient-specific tumor neoantigens to induce T-cell responses and potentiate antitumor activity. We report mechanistic insights into the immunogenicity of mRNA-4157 via characterization of T-cell responses to neoantigens from the first-in-human, phase 1, KEYNOTE-603 study (NCT03313778) in patients with resected non-small cell lung cancer (Part A: 1-mg mRNA-4157, n = 4) or resected cutaneous melanoma (Part D: 1-mg mRNA-4157 + 200-mg pembrolizumab, n = 12). Safety, tolerability, and immunogenicity were assessed. All patients experienced ≥1 treatment-emergent adverse event; there were no grade 4/5 adverse events or dose-limiting toxicities. mRNA-4157 alone induced consistent de novo and strengthened preexisting T-cell responses to targeted neoantigens. Following combination therapy, sustained mRNA-4157-induced neoantigen-specific T-cell responses and expansion of cytotoxic CD8 and CD4 T cells were observed. These findings show the potential of a novel mRNA individualized neoantigen therapy approach in oncology. Significance: The safety and immunogenicity results from this phase 1 study of mRNA-4157 as adjuvant monotherapy or combination therapy with pembrolizumab show generation of de novo and enhancement of existing neoantigen-specific T-cell responses and provide mechanistic proof of concept to support further development of mRNA-4157 for patients with resected solid tumors. See related commentary by Berraondo et al., p. 2021.</p>","PeriodicalId":9430,"journal":{"name":"Cancer discovery","volume":" ","pages":"2209-2223"},"PeriodicalIF":29.7,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141901036","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":"Drugging p53: Barriers, Criteria, and Prospects.","authors":"Huaxin Song, Shujun Xiao, Jiaqi Wu, Min Lu","doi":"10.1158/2159-8290.CD-24-0837","DOIUrl":"https://doi.org/10.1158/2159-8290.CD-24-0837","url":null,"abstract":"<p><p>Pharmacologically targeting tumor suppressors necessitates an unprecedented strategy of restoring, rather than conventionally inhibiting, protein function, and p53, the most commonly mutated protein in cancer, has thus remained undruggable. In this study, we address long-standing misconceptions in the field and gaps in the scientific logic for a p53 function-restoration strategy, identify four barriers for drugging mutant p53, and accordingly propose effectiveness evaluation criteria, clinical-translating norms, and prospects for mutant p53 rescue compounds.</p>","PeriodicalId":9430,"journal":{"name":"Cancer discovery","volume":"14 11","pages":"2055-2060"},"PeriodicalIF":29.7,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142557237","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":"Rational Protein Engineering to Enhance MHC-Independent T-cell Receptors.","authors":"Ju-Fang Chang, Jack H Landmann, Tien-Ching Chang, Mehmet Emrah Selli, Yangdon Tenzin, John M Warrington, Julie Ritchey, Yu-Sung Hsu, Michael Slade, Deepesh Kumar Gupta, John F DiPersio, Alex S Holehouse, Nathan Singh","doi":"10.1158/2159-8290.CD-23-1393","DOIUrl":"10.1158/2159-8290.CD-23-1393","url":null,"abstract":"<p><p>Chimeric antigen receptor (CAR)-based therapies have pioneered synthetic cellular immunity but remain limited in their long-term efficacy. Emerging data suggest that dysregulated CAR-driven T-cell activation causes T-cell dysfunction and therapeutic failure. To re-engage the precision of the endogenous T-cell response, we designed MHC-independent T-cell receptors (miTCR) by linking antibody variable domains to T-cell receptor constant chains. Using predictive modeling, we observed that this standard \"cut and paste\" approach to synthetic protein design resulted in myriad biochemical conflicts at the hybrid variable-constant domain interface. Through iterative modeling and sequence modifications, we developed structure-enhanced miTCRs which significantly improved receptor-driven T-cell function across multiple tumor models. We found that 41BB costimulation specifically prolonged miTCR T-cell persistence and enabled improved leukemic control in vivo compared with classic CAR T cells. Collectively, we have identified core features of hybrid receptor structure responsible for regulating function. Significance: Improving the durability of engineered T-cell immunotherapies is critical to enhancing efficacy. We used a structure-informed design to evolve improved miTCR function across several models. This work underscores the central role of synthetic receptor structure in T-cell function and provides a framework for improved receptor engineering.</p>","PeriodicalId":9430,"journal":{"name":"Cancer discovery","volume":" ","pages":"2109-2121"},"PeriodicalIF":29.7,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11530325/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141562643","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The N6-methyladenosine Epitranscriptomic Landscape of Lung Adenocarcinoma.","authors":"Shiyan Wang, Yong Zeng, Lin Zhu, Min Zhang, Lei Zhou, Weixiong Yang, Weishan Luo, Lina Wang, Yanming Liu, Helen Zhu, Xin Xu, Peiran Su, Xinyue Zhang, Musaddeque Ahmed, Wei Chen, Moliang Chen, Sujun Chen, Mykhaylo Slobodyanyuk, Zhongpeng Xie, Jiansheng Guan, Wen Zhang, Aafaque Ahmad Khan, Shingo Sakashita, Ni Liu, Nhu-An Pham, Paul C Boutros, Zunfu Ke, Michael F Moran, Zongwei Cai, Chao Cheng, Jun Yu, Ming S Tsao, Housheng H He","doi":"10.1158/2159-8290.CD-23-1212","DOIUrl":"10.1158/2159-8290.CD-23-1212","url":null,"abstract":"<p><p>Comprehensive N6-methyladenosine (m6A) epitranscriptomic profiling of primary tumors remains largely uncharted. Here, we profiled the m6A epitranscriptome of 10 nonneoplastic lung tissues and 51 lung adenocarcinoma (LUAD) tumors, integrating the corresponding transcriptomic, proteomic, and extensive clinical annotations. We identified distinct clusters and genes that were exclusively linked to disease progression through m6A modifications. In comparison with nonneoplastic lung tissues, we identified 430 transcripts to be hypo-methylated and 222 to be hyper-methylated in tumors. Among these genes, EML4 emerged as a novel metastatic driver, displaying significant hypermethylation in tumors. m6A modification promoted the translation of EML4, leading to its widespread overexpression in primary tumors. Functionally, EML4 modulated cytoskeleton dynamics by interacting with ARPC1A, enhancing lamellipodia formation, cellular motility, local invasion, and metastasis. Clinically, high EML4 protein abundance correlated with features of metastasis. METTL3 small-molecule inhibitor markedly diminished both EML4 m6A and protein abundance and efficiently suppressed lung metastases in vivo. Significance: Our study reveals a dynamic and functional epitranscriptomic landscape in LUAD, offering a valuable resource for further research in the field. We identified EML4 hypermethylation as a key driver of tumor metastasis, highlighting a novel therapeutic strategy of targeting EML4 to prevent LUAD metastasis.</p>","PeriodicalId":9430,"journal":{"name":"Cancer discovery","volume":" ","pages":"2279-2299"},"PeriodicalIF":29.7,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11528209/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141449754","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting Noncoding cis-Regulatory Elements for Cancer Therapy in the Context of the 3D Genome.","authors":"Kailong Li, Gong-Hong Wei, Yuxin Yin, Jiawen Feng","doi":"10.1158/2159-8290.CD-24-0836","DOIUrl":"https://doi.org/10.1158/2159-8290.CD-24-0836","url":null,"abstract":"<p><p>Significant efforts have been made to identify and validate oncoproteins and ncRNAs as therapeutic targets for cancer therapy; however, emerging observations suggest that noncoding cis-regulatory elements, which orchestrate the 3D organization of the genome and thus the transcriptional landscape, are potential therapeutic targets as well. In this commentary, we envisage that further efforts to decipher the noncoding cis-regulatory code and performing systematic surveys of functional noncoding cis-regulatory elements and recurrent 3D genome alterations in both cancerous and nonmalignant cells within tumor tissues will pave the way to the development of novel therapeutic strategies.</p>","PeriodicalId":9430,"journal":{"name":"Cancer discovery","volume":"14 11","pages":"2061-2065"},"PeriodicalIF":29.7,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142557243","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}