Molecular and Cellular Biology / Genetics最新文献

{"title":"Abstract 2261: A multimodal single-cell workflow to interrogate cellular responses to cancer therapy","authors":"Dalia M. Dhingra, A. Ooi, Alex Li, A. Sciambi, Shu Wang, Saurabh Gulati, D. Ruff","doi":"10.1158/1538-7445.AM2021-2261","DOIUrl":"https://doi.org/10.1158/1538-7445.AM2021-2261","url":null,"abstract":"","PeriodicalId":18754,"journal":{"name":"Molecular and Cellular Biology / Genetics","volume":"68 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90659329","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Abstract LB012: Efficacy of atezolizumab in the treatment of solid tumors with high tumor mutational burden (TMB): A MyPathway study cohort","authors":"J. Hainsworth, C. Friedman, R. Kurzrock, D. Spigel, H. Burris, C. Sweeney, F. Meric-Bernstam, Yong Wang, Jonathan Levy, D. Shames, K. Schulze, Arisha Patel, C. Swanton","doi":"10.1158/1538-7445.AM2021-LB012","DOIUrl":"https://doi.org/10.1158/1538-7445.AM2021-LB012","url":null,"abstract":"Purpose Data suggest that TMB is correlated with response to checkpoint blockade. We present an analysis of atezolizumab treatment of patients (pts) with advanced solid tumors and high TMB from MyPathway (NCT02091141), a multi-basket study assessing activity of FDA-approved therapies in non-indicated tumors with targetable alterations. Methods Eligible pts were ≥18 years old with previously treated advanced solid tumors with TMB ≥10 mut/Mb by any CLIA-certified assay. Pts received atezolizumab 1200 mg IV q3w. The pre-planned primary endpoint was objective response rate (ORR) in pts with TMB ≥16 mut/Mb by FoundationOne CDx (F1CDx), a threshold determined by a retrospective study that showed TMB ≥16 mut/Mb is associated with improved ORR and duration of response (DOR) for various tumor types. Other endpoints in this group included disease control rate (DCR), DOR, progression-free survival (PFS), and overall survival (OS). Separate analyses were performed in pts with TMB ≥10 and Results Enrollment closed on 7-9-20. By the 12-11-20 data cutoff, 118 pts with 20 tumor types and TMB ≥10 mut/Mb by any CLIA assay were evaluable for efficacy. In the primary efficacy population of 42 pts with TMB ≥16 mut/Mb by F1CDx, confirmed investigator-assessed ORR was 38.1% vs 2.1% in 48 pts with TMB ≥10 mut/Mb and Conclusions Atezolizumab had durable activity against diverse solid tumor types with TMB ≥16 mut/Mb, independent of MSI status. Limited activity was observed in tumors with TMB ≥10 and Citation Format: John Hainsworth, Claire F. Friedman, Razelle Kurzrock, David R. Spigel, Howard Burris, Christopher J. Sweeney, Funda Meric-Bernstam, Yong Wang, Jonathan Levy, David Shames, Katja Schulze, Arisha Patel, Charles Swanton. Efficacy of atezolizumab in the treatment of solid tumors with high tumor mutational burden (TMB): A MyPathway study cohort [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr LB012.","PeriodicalId":18754,"journal":{"name":"Molecular and Cellular Biology / Genetics","volume":"20 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90779917","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Abstract 2351: Multiomics integration elucidates onco-metabolic modulators of drug resistance in lymphoma","authors":"S. Singh, Fouad Choueiry, Amber Hart, A. Sircar, Jiangjiang Zhu, L. Sehgal","doi":"10.1158/1538-7445.AM2021-2351","DOIUrl":"https://doi.org/10.1158/1538-7445.AM2021-2351","url":null,"abstract":"","PeriodicalId":18754,"journal":{"name":"Molecular and Cellular Biology / Genetics","volume":"37 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91090580","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Abstract 1932: Talazoparib interacts with oncolytic reovirus to enhance death-inducing signaling complex (DISC)-mediated apoptosis and immune response","authors":"J. Kyula, V. Roulstone, R. Elliott, H. Whittock, G. Bozhanova, M. McLaughlin, M. Pedersen, Dragomir B. Krastev, S. Pettitt, Arnaud J. Legrand, T. Tenev, James C. Wright, Lu Yu, J. Choudhary, P. Meier, C. Lord, A. Melcher, G. Wilkinson, M. Coffey, K. Harrington","doi":"10.1158/1538-7445.AM2021-1932","DOIUrl":"https://doi.org/10.1158/1538-7445.AM2021-1932","url":null,"abstract":"","PeriodicalId":18754,"journal":{"name":"Molecular and Cellular Biology / Genetics","volume":"26 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89429031","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Abstract 2040: Analysis of DNA damage repair gene alterations and their association with tumor mutation burden in 1427 hepatocellular carcinoma patients","authors":"Mengmei Yang, W. Xie, Mengli Huang, Xinhua Zhu","doi":"10.1158/1538-7445.AM2021-2040","DOIUrl":"https://doi.org/10.1158/1538-7445.AM2021-2040","url":null,"abstract":"","PeriodicalId":18754,"journal":{"name":"Molecular and Cellular Biology / Genetics","volume":"75 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90827144","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Abstract 2118: Non-coding germline GATA3 variants alter chromatin topology and contribute to pathogenesis of acute lymphoblastic leukemia","authors":"Hongbo Yang, Hui Zhang, Yu Luan, Tingting Liu, K. Roberts, Maoxiang Qian, Bo Zhang, Wenjian Yang, V. Pérez-Andreu, Jie Xu, Sriranga lyyanki, Da Kuang, S. Reshmi, J. Gastier-Foster, Colton A. Smith, C. Pui, W. Evans, S. Hunger, L. Platanias, M. Relling, C. Mullighan, M. Loh, Feng Yue, Jun J. Yang","doi":"10.1158/1538-7445.AM2021-2118","DOIUrl":"https://doi.org/10.1158/1538-7445.AM2021-2118","url":null,"abstract":"Inherited non-coding genetic variants confer significant disease susceptibility in many cancers. However, the molecular processes of by which germline variants contribute to somatic lesions are poorly understood. We performed targeted sequencing in 5,008 patients and identified a key regulatory germline variant in GATA3 strongly associated with Philadelphia chromosome-like acute lymphoblastic leukemia (Ph-like ALL). By creating an isogenic cellular model with CRISPR-Cas9 system, we showed that this variant activated a strong enhancer that significantly upregulated GATA3 transcription, which in turn reshaped the global chromatin accessibility and 3D genome organization. Remarkably, this genotype switch induced a chromatin loop between the CRLF2 oncogene and a distal enhancer, similar to the somatically acquired super-enhancer hijacking event in patients. GATA3 genotype-related alterations in transcriptional control and 3D chromatin organization were further validated in Ph-like ALL patients. Finally, we showed that GATA3 directly regulates CRLF2 and potentiates the oncogenic effects of JAK-STAT signaling in leukemogenesis. Altogether, our results provide evidence for a novel mechanism by which a germline non-coding variant contributes to oncogene activation epigenetic regulation and 3D genome reprogramming. Citation Format: Hongbo Yang, Hui Zhang, Yu Luan, Tingting Liu, Kathryn Roberts, Mao-xiang Qian, Bo Zhang, Wenjian Yang, Virginia Perez-Andreu, Jie Xu, Sriranga lyyanki, Da Kuang, Shalini Reshmi, Julie Gastier-Foster, Colton Smith, Ching-Hon Pui, William Evans, Stephen Hunger, Stephen Hunger, Leonidas Platanias, Mary Relling, Charles Mullighan, Mignon Loh, Feng Yue, Jun Yang. Non-coding germline GATA3 variants alter chromatin topology and contribute to pathogenesis of acute lymphoblastic leukemia [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2118.","PeriodicalId":18754,"journal":{"name":"Molecular and Cellular Biology / Genetics","volume":"26 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89587767","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Abstract 1950: A ubiquitination cascade regulates the integrated stress response and epithelial cancer survival","authors":"Lisa D. Cervia, T. Shibue, Benjamin Gaeta, Ashir A. Borah, Lisa Leung, Naomi Li, N. Dumont, Alfredo Gonzalez, Nolan R. Bick, M. Kazachkova, Joshua M. Dempster, J. Krill-Burger, N. Udeshi, M. Olive, S. Carr, D. Root, F. Piccioni, James M. McFarland, F. Vazquez, William C. Hahn","doi":"10.1158/1538-7445.AM2021-1950","DOIUrl":"https://doi.org/10.1158/1538-7445.AM2021-1950","url":null,"abstract":"","PeriodicalId":18754,"journal":{"name":"Molecular and Cellular Biology / Genetics","volume":"84 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76854868","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Abstract 1923: Modulation of apoptosis in glioblastoma U87-MG cancer cells by aqueous extract ofBryophyllum pinnatum","authors":"K. Ferrer, Joshua Li, Camille Kordas, Jasmine Cha, S. Han, Joon Seo, Nathaly Manrique, Minseo Kang, Y. Jin, Si Won Choi, Ben Hiramoto, Denise L. Smith, B. Y. Wong","doi":"10.1158/1538-7445.AM2021-1923","DOIUrl":"https://doi.org/10.1158/1538-7445.AM2021-1923","url":null,"abstract":"Bryophyllum pinnatum (BP) has been used in anthroposophic medicine to treat “hyperactivity diseases” such as tocolytic symptom and overactive bladder syndrome since the beginning of 20th century with no side effect. Its major secondary metabolites include bufadienolides, flavonoids, triterpenes, and steroids. BP has been widely used in tropical regions as traditional medicine. It is reported to have antioxidant, immunomodulatory, antidiabetic, anti-inflammatory, antihypertensive, wound healing, cytotoxic, and antitumor promoting activities. Glioblastoma is an aggressive and lethal tumor of the brain with few treatment options. In this study, the effects of aqueous extracts of BP on the induction and modulation of apoptosis in glioblastoma U87-MG cells were assessed using the green/red/blue fluorescent Apoptosis/Necrosis Detection Kit and the Human Apoptosis Antibody Array - Membrane (43 Targets) test by the Abcam cooperation. Our data revealed that 3-hours of 1 mg/mL and 2 mg/mL BP treatment induced statistically similar amounts of apoptosis observed as green apoptotic cells and red necrotic cells in U87-MG cells respectively (apoptotic cells = 86.0 ± 6%, necrotic cells = 14.0 ± 6.0% ; apoptotic cells = 85.0 ± 4.0% , necrotic cells = 14.5 ± 3.5%). The percent of apoptosis was not significantly different as compared to that of the positive control induced by 1µMol Staurosporine (94.5 ± 0.5%, 5.5 ± 0.5%); while significantly different from the negative control which had none apoptotic cells. Slightly less induction of apoptosis was obtained from 6-hours of 1 mg/mL and 2 mg/mL BP treatment with more necrotic cells (81.5 ± 2.5%, 18.5 ± 2.5%; 78.0 ± 3.0%, 21.5 ± 2.5% respectively). Modulation of various apoptosis markers such as up-regulation of Bax, p53, Caspase 3; and down-regulation of Bcl-2 and Bcl-w was also observed. These results suggest that BP contains phytochemicals which induce apoptosis in glioblastoma U87-MG cells by modulating these apoptotic pathway markers. Further study of the specific modulation effects of BP on apoptosis is warranted to reveal its potential chemopreventive and therapeutic properties against glioblastoma and other cancers. Citation Format: Kristin Ferrer, Joshua Li, Camille Kordas, Jasmine Cha, Sung Been Han, Joon Seo, Nathaly Manrique, Min Seo Kang, Yi Shan Jin, Si Won Choi, Ben Hiramoto, Denise Smith, Brian Yuen Wong. Modulation of apoptosis in glioblastoma U87-MG cancer cells by aqueous extract of Bryophyllum pinnatum [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 1923.","PeriodicalId":18754,"journal":{"name":"Molecular and Cellular Biology / Genetics","volume":"42 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78541731","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Abstract 2109: The bromodomain-containing protein ATAD2 promotes GR-mediated enzalutamide resistance in castration-resistant prostate cancer","authors":"Richard De La Rosa","doi":"10.1158/1538-7445.AM2021-2109","DOIUrl":"https://doi.org/10.1158/1538-7445.AM2021-2109","url":null,"abstract":"The purpose of this study is to investigate how the activity of the glucocorticoid receptor (GR) is orchestrated to drive the development of enzalutamide resistance in metastatic, castration resistant prostate cancer (mCRPC). Enzalutamide (Enz) is the second-generation antagonist of the androgen receptor, the fuel for the development and progression of prostate cancer. Even though enzalutamide is an effective and well-tolerated treatment in a broad spectrum of patients with castration-resistant prostate cancer, almost all the patients become resistant to the drug eventually. One of the plausible mechanisms to account for the development of enzalutamide resistance is the activation of GR signaling. Upon Enz treatment, GR is upregulated, binds to the cis-regulatory elements of some AR target genes, activates the transcription of these downstream genes and thus circumvents the inhibitory effect of the AR antagonist on prostate cancer cell growth. Unfortunately, it is still unknown how GR-mediated enzalutamide resistance is controlled. Recently, a group of epigenetic regulators, bromodomain (BRD)-containing proteins, have been indicated to promote prostate cancer progression. They function as AR cofactors and dictate the transcriptional activity of the nuclear receptor in response to different ligands. Our prior work found that one of the BRD family members, called ATAD2, plays an essential role in orchestration of GR signaling in the presence of enzalutamide. ATAD2 is significantly elevated upon GR activation and positively regulates GR expression in return. Coimmunoprecipitation demonstrated that ATAD2 binds to GR in enzalutamide-resistant CRPC cells, and it is required for the GR-dependent transcriptional reprogramming in the presence of Enz. Most importantly, we demonstrated that CRPC cells that are Enz-refractory due to the activation of GR signaling become Enz sensitive when ATAD2 is depleted All these findings suggest that ATAD2 acts as a cofactor for GR to induce a gene expression pattern that results in Enz-refractory phenotype in CRPC cells. Our work will not only provide an in-depth insight into the mechanisms underlying enzalutamide resistance, but also lay the foundation for the development of novel therapeutic strategies targeting glucocorticoid receptor (GR) signaling to treat this lethal disease. Citation Format: Richard De La Rosa. The bromodomain-containing protein ATAD2 promotes GR-mediated enzalutamide resistance in castration-resistant prostate cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2109.","PeriodicalId":18754,"journal":{"name":"Molecular and Cellular Biology / Genetics","volume":"16 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75161458","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Abstract 2221: Whole transcriptome sequencing reveals oncogenic fusions in melanoma","authors":"S. Darabi, A. Elliott, David Braxton, J. Zeng, K. Poorman, J. Swensen, G. Gibney, J. Moser, T. Phung, M. Atkins, G. In, W. Korn, B. Eisenberg, M. Demeure","doi":"10.1158/1538-7445.AM2021-2221","DOIUrl":"https://doi.org/10.1158/1538-7445.AM2021-2221","url":null,"abstract":"Introduction: Oncogenic gene fusions are frequently identified in different cancers; however, the exact incidence of oncogenic fusions in melanoma is not well defined. Several targeted therapies are approved and considered the standard of care for patients whose solid or hematologic tumors harbor particular gene fusions, but their role as targets in melanoma also remains undelineated. We sought to determine the prevalence of oncogenic fusions in metastatic or locally advanced melanoma. Methods: We retrospectively analyzed data from formalin-fixed paraffin-embedded (FFPE) tumor samples sent to a commercial CLIA-certified laboratory (Caris Life Sciences) from February 2019 to July 2020. Samples were profiled by next-generation sequencing of a 592-gene DNA panel, whole transcriptome sequencing, and immunohistochemistry (IHC). Results: Melanoma specimens were analyzed from 1,255 subjects, of whom 478 (38.1%) were female and 777 (61.9%) were male, with a median age of 67 years. Of these specimens, 780 (63.1%) were from metastatic sites. We identified 33 (2.6%) cases with in-frame oncogenic fusions (14 novel) including 21 BRAF fusions and 4 RAF1 fusions, as well as fusions involving PRKCA (n=4), TERT (n=2), AXL (n=1), and FGFR3 (n=1). PD-L1 expression by IHC (SP142 or 28-8 antibody) was detected in 512 (42.5%) specimens, including 10 (32.3%) of the fusion-positive tumors, while 572 (47.4%) specimens were TMB-High (≥10 mutations/Mb), including 11 (33.3%) of the fusion-positive tumors, suggesting these patients may respond to immunotherapy. We identified 796 (63.4%) cases with RAS/RAF pathogenic or likely pathogenic mutations, including 373 (30.0%) BRAF p.V600X mutations. With the exception of a single BRAF p.S467L (Class 3, “kinase-dead”) mutation, the absence of BRAF mutations in BRAF fusion-positive tumors suggests these fusions are oncogenic drivers. However, tumors harboring PRKCA and TERT fusions were each detected with at least one MAPK pathway co-alteration (NRAS, NF1, or BRAF p.V600E mutation). Fusion transcripts with unknown pathogenicity were also detected in 668 (53.2%) cases. RNA expression analysis of key molecular pathways (including Wnt/β-catenin, PI3K/AKT/MTOR, DNA repair, INFG, and JAK/STAT) showed a high degree of variability among fusion-positive tumors and other mutational subgroups, which may reflect the heterogeneity common to melanoma, prior treatments or development of various resistance mechanisms. Conclusions: Oncogenic gene fusions are rare in melanoma when compared with other genetic variants. We identified potentially actionable fusions as well as co-alterations in fusion-positive cases, with notably mutual exclusivity of BRAF fusions and p.V600X mutations. The data suggest that targetable variants, including oncogenic fusions, may be identified in melanoma with comprehensive tumor profiling and provide patients with personalized treatment or clinical trial options. Citation Format: Sourat Darabi, Andrew Elliott, David R. Br","PeriodicalId":18754,"journal":{"name":"Molecular and Cellular Biology / Genetics","volume":"27 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77967240","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}