bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract LB-104: Epigenetic and transcriptional alterations as potential vulnerabilities of diffuse intrinsic pontine glioma (DIPG)
Authors: Yu Jia-Ray , LeRoy Gary , Stafford James , Lee Chul-Hwan , Reinberg Danny 
Published: August 2019

Abstract
A methionine substitution at lysine-27 on histone H3 variants (H3K27M) is present in more than 80% of diffuse intrinsic pontine gliomas (DIPG) and inhibits polycomb repressive complex 2 (PRC2) in a dominant-negative fashion. We discovered that a number of parameters were involved in H3K27M-dependent inhibition of PRC2, including the ratio between H3K27M and PRC2 present in vivo, an enhanced affinity between H3K27M and the allosterically activated state of PRC2, and the displacement of PRC2 from chromatin containing H3K27M. Following these early events upon an introduction of H3K27M into wildtype cells, the steady-state chromatin manifested a global loss of H3K27 methylation but a gain of H3K36 methylaiton, an antagonistic histone modification associated with transcriptional elongation. These observations suggested that H3K36 methylation may function in displacing PRC2 from chromatin and the oncogenic transcription facilitated by H3K36 methylation could be a vulnerability of H3K27M DIPG. Indeed, ectopic expression of H3K36M in H3K27M DIPG cells depleted global H3K36 methylation and exerted an anti-proliferative effect, implicating a potential strategy in targeting the writer and reader proteins for H3K36 methylation against H3K27M DIPG.
Citation Format: Jia-Ray Yu, Gary LeRoy, James Stafford, Chul-Hwan Lee, Danny Reinberg. Epigenetic and transcriptional alterations as potential vulnerabilities of diffuse intrinsic pontine glioma (DIPG) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr LB-104.
Abstract LB-115: Preclinical assessment of retinoid X-receptor agonist, UAB110, for potential treatment of cutaneous T-cell lymphoma
Authors: Chou Chu-Fang , Esla Jason , Atigadda Venkatram , Muccio Donald , Grubbs Clinton , Craig Elmets , Chang Pi-Ling 
Published: August 2019

Abstract
Cutaneous T-cell lymphomas (CTCLs) are a group of non-Hodgkin diseases characterized by localization of neoplastic T-cells in the skin. The most common forms of CTCLs are mycosis fungoides (MF) and Sézary syndrome (SS). Bexarotene (Targretin®) is currently the only FDA approved retinoid X receptor (RXR) -selective agonist (rexinoid) for the treatment of CTCLs. Despite its low toxicity compared to retinoids and other chemotherapeutic agents, it induces hypothyroidism and markedly elevates serum triglycerides (TGs). Thus, improved rexinoids for the treatment of this indolent disease is necessary. A potential candidate is the novel rexinoid, UAB110, which does not elevate TGs in animal studies and effectively prevents mammary cancer development. Compared to bexarotene, it has higher binding affinity for RXRα receptor and transcriptional activation activity. The purpose of this study is to assess preclinical efficacy, mechanism of action of UAB110, and compare its action with bexarotene and the rexinoid 9-cisUAB30 (UAB30) using human-derived CTCL cell lines, MyLa and HuT78, which are representative of MF and SS, respectively. Cell proliferation analysis and cell-cycle related markers were determined by hemocytometer and Western blot analysis, respectively. UAB110 is as effective as UAB30 and bexarotene in suppressing cell proliferation. Furthermore, it significantly (p &lt; 0.05 relative to DMSO control) suppresses the protein expression of SKP2 (S-phase kinase-associated protein 2, a F-box protein that targets p27kip1 for degradation by 26S proteasome) and PSMA7 (proteasome subunit alpha type 7, a component of the 20S proteolytic complex in 26S proteasome). The decrease in SKP2 resulted in a concomitant up-regulation of p27kip1 protein, the major cell cycle inhibitor. The downregulating of PSMA7 impaired the 20S proteasome activity in both cell lines. These findings indicate that the novel rexinoid is effective in inhibiting cell proliferation of CTCL cells, in part, by suppressing SKP2 expression and the 20S proteasome activity resulting in increasing p27kip1 protein. In sum, UAB110 and also UAB30 with minimal effect in elevating serum TGs are both possible alternatives to bexarotene for the treatment of CTCLs.
Citation Format: Chu-Fang Chou, Jason Esla, Venkatram Atigadda, Donald Muccio, Clinton Grubbs, Elmets Craig, Pi-Ling Chang. Preclinical assessment of retinoid X-receptor agonist, UAB110, for potential treatment of cutaneous T-cell lymphoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr LB-115.
Abstract LB-126: S100A14 promotes breast cancer metastasis via CCL2 dependent macrophage recruitment
Authors: Chen Hongyan , Li Xukun , Liu Zhihua 
Published: August 2019

Abstract
S100A14 is a member of S100 calcium-binding protein family. Our previous studies have reported that S100A14 modulates a variety of tumorigenic processes by functioning both as intracellular and extracellular factors. Emerging evidence indicated that the biology of most S100 proteins is complex and multifactorial. Herein, we identify S100A14 is upregulated in Lymph Node (LN) metastasis breast cancer (BC) and associated with LN metastasis and prognosis. Through gain and loss of function approaches, we find that S100A14 promotes cell migratory and invasive capabilities in vitro and lung metastasis in vivo. More convincingly, S100A14 knockout also suppresses the lung metastases without affecting the primary tumor growth in MMTV-PyMT mouse models. Using a combination of iTRAQ based quantitative proteomics and transcriptomics, we identified CCL2 as a downstream target of S100A14. Importantly, systemic delivery of anti-CCL2 antibody significantly inhibited S100A14-enhanced cell migration and invasion, tumor-associated macrophages (TAMs) accumulation and lung metastasis. Finally, we indicated that the increased serum S100A14 levels could be used for the detection of BC and the prediction of LN metastases. These findings provide a plausible mechanism for S100A14-modulated tumor microenvironment in metastasis and show that S100A14-mediated CCL2 signaling plays a prominent role in breast cancer metastasis, which may have clinical implications for providing novel biomarkers and potential therapeutic targets of breast cancer in future.
Note: This abstract was not presented at the meeting.
Citation Format: Hongyan Chen, Xukun Li, Zhihua Liu. S100A14 promotes breast cancer metastasis via CCL2 dependent macrophage recruitment [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr LB-126.
Abstract LB-137: Three-dimensional cytotoxicity assay using magnetic 3D bioprinting for measuring CAR T cell function in heterogeneous solid tumor microenvironments
Authors: Souza Glauco R. , Najjar Amer 
Published: August 2019

Abstract
Chromium release assays are routinely utilized to assess cytotoxic activity and function of tumor targeting T cells expressing chimeric antigen receptors (CAR T cells). Although these assays can predict the activity of CAR T cells targeting hematological malignancies, results of such assays do not accurately reflect the limited efficacy of T cell therapy observed against solid tumors. This limitation may be due to the disparity between the in vitro cell culture setting and the complex nature of solid tumor microenvironments and their vascular structure. To this end, we have developed a cytotoxicity assay based on a three-dimensional (3D) cell culture model, facilitated by magnetic 3D bioprinting, to more precisely mimic the complexity of solid tumor microenvironments in vitro. This model can be customized to reflect the heterogeneity of solid tumors by incorporating multiple cell types and immune cells. In these studies, we have demonstrated the feasibility of this assay using CD19-specific CAR T cells specifically targeting CD19+ leukemia cells in a heterogeneous 3D cell culture. We also show the CAR T cells infiltrating and targeting glioblastoma (U87) 3D cultures in real-time with fluorescence microscopy. Incorporation of this assay as a routine cytotoxicity assay will provide new dimensions to rapid immune function assessments by revealing the kinetics of cell killing through time-lapse microscopy, the persistence and targeting patterns of CAR T cells, and cell-specific killing by multicolor fluorescence imaging. This assay is being adapted into a 96-, 384- and 1,536-well formats for high-throughput applications.
Citation Format: Glauco R. Souza, Amer Najjar. Three-dimensional cytotoxicity assay using magnetic 3D bioprinting for measuring CAR T cell function in heterogeneous solid tumor microenvironments [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr LB-137.
Abstract LB-144: Deletion of Map4k4 enhances CD8 T cell function
Authors: Esen Emel , Ye Weilan , Jesudason Rajiv , Sergin Ismail 
Published: August 2019

Abstract
Map4k4 is broadly expressed across different cell types and its function is cell type and context dependent. Although it is expressed in multiple types of immune cells, its specific function in different subsets of lymphocytes and myeloid cells have yet to be determined. Here we demonstrate that reducing MAP4K4 activity can enhance CD8 T cell functions in the context of anti-tumor and anti-viral responses. Inducible deletion of Map4k4 increases CD8 T cell activation, proliferation, cytokine production, and target cell killing in vitro, and enhances CD8 T cell-mediated suppression of tumor growth as well as antigen-specific response to viral infection in vivo. Intratumoral T cells showed evidence of enhanced activation and produced more inflammatory cytokines when stimulated ex vivo. Simultaneously reducing MAP4K4 activity and blocking PDL1 resulted in additive anti-tumor efficacy. Our data suggests that MAP4K4 could be a potential target to augment anti-tumor and immunity.
Citation Format: Emel Esen, Weilan Ye, Rajiv Jesudason, Ismail Sergin. Deletion of Map4k4 enhances CD8 T cell function [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr LB-144.
Abstract LB-145: Investigation of T cell dynamic changes in tumor progression by using sing-cell data
Authors: Zhang Hongyi , Liu Longchao , Chen Jiahui , Li Bo 
Published: August 2019

Abstract
Cancer immunotherapies have revolutionized the treatment of cancer. To better understand the dynamic changes of T cell states during tumor progression, we profiled TCR sequences and transcriptomes of ~40,000 T cells from matched xenograft MC38 cancer cell line and spleen samples of 12 mice. Comparing the gene expression profiles of T cells collected in 10-day and 20-day samples, we observed obvious differences of T cell composition, such as higher CD8 and lower CD4 T cells in 20-day tumors. Unsupervised clustering revealed two subsets of T cells specific to early tumors, recapitulating important markers, such as TCF7, which has recently been reported to be a valid predictor of immune checkpoint blockade therapies in melanoma. Additionally, a unique CD8 cluster, expressing markers of T cell activation and exhaustion, was found to appear only in late tumors. We also observed subpopulations of TCRαβ+ CD3+/CD4-/CD8- double negative (DN) T cells, which have not been well-characterized in the tumor microenvironment. Our analysis revealed three clusters of DN cells: 1) an effector-like group with FCER1G and XCL1 high expression, and high interferon production; 2) a regulatory population expressing high level of Foxp3 and IL2ra, which has been previously reported in autoimmune disorders; 3) a naïve-like population with CCR7 expression. These findings indicate that the DN T cell population may span a wide-spectrum of functionalities that similar to CD4 or CD8 single positive conventional T cells. Our study, for the first time, provided a high-resolution dynamic landscape of T cell state and identified rare T cell subgroups associated with cancer progression.
Citation Format: Hongyi Zhang, Longchao Liu, Jiahui Chen, Bo Li. Investigation of T cell dynamic changes in tumor progression by using sing-cell data [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr LB-145.
Abstract LB-161: Application of the ASCO and ESMO frameworks to TTFields treatment of mesothelioma
Authors: Kelly Justin , Weinberg Uri , Proescholdt Christina 
Published: August 2019

Abstract
Objective: To assess the clinical value of tumor treating fields (TTFields) in malignant pleural mesothelioma (MPM) by means of the ASCO and ESMO frameworks.
Background: The potential effectiveness and safety of TTFields in addition to pemetrexed and cisplatin or carboplatin in MPM was recently shown by the analysis of the Phase II single arm EF-23 STELLAR trial. To account for the need of physicians and policymakers to objectively and comparably capture the clinical value of new cancer treatments the American Society of Clinical Oncology (ASCO) and the European Society for Medical Oncology (ESMO) have both developed assessment frameworks. We quantified the clinical value of the TTFields treatment in MPM by applying ASCO and ESMO frameworks to the comparison of the STELLAR data to historical controls.
Materials/Methods: The EF-23 STELLAR Trial (n=80) demonstrated that adding TTFields to pemetrexed and cisplatin or carboplatin for malignant pleural mesothelioma patients resulted in overall survival of 18.2 months (95% CI 12.1-25.8) and progression free survival of 7.6 months (95% CI 6.7-8.6). The ESMO Magnitude of Clinical Benefit Scale (MCBS) and the ASCO Net Health Benefit (NHB) frameworks were applied to the EF-23 trial data using a historical control as comparator.
Results: The application of the ASCO framework to the EF-23 data resulted in a NHB score of 52. This result was at the higher end of the score range of novel cancer treatments and compares well to the results for nivolumab in advanced non-squamous NSCLC and advanced squamous NSCLC as reference points. Applying the ESMO framework resulted in MCBS scores of A/5 (adjuvant/advanced) which would be the first score reported for MPM. The MCBS scores of A/5 are the highest scores achievable in the ESMO framework, and higher then the ESMO MCBS scores reported in the literature for NSCLC treatments.
Conclusions: Despite differences in their respective concepts, both the ASCO and ESMO frameworks suggest that adding TTFields to Pemetrexed and Cisplatin or Carboplatin in malignant pleural mesothelioma patients may provide a significant clinical benefit. The high scores underline the fact that treatment with TTFields may extended progression free and overall survival without additional systemic toxicities.
Citation Format: Justin Kelly, Uri Weinberg, Christina Proescholdt. Application of the ASCO and ESMO frameworks to TTFields treatment of mesothelioma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr LB-161.
Abstract LB-163: Comparing clinical value scores (NCCN, ASCO and ESMO) for TTFields treatment in glioblastoma
Authors: Kelly Justin , Proescholdt Christina , Blondin Nicholas A. 
Published: August 2019

Abstract
Objective: To compare the tools of the National Comprehensive Cancer Network (NCCN), American Society of Clinical Oncology (ASCO) and the European Society for Medical Oncology (ESMO) for the assessment of the clinical value for Tumor treating fields (TTFields) in newly diagnosed Glioblastoma (GBM).
Background: The effectiveness and safety of TTFields in newly diagnosed GBM was demonstrated by the final analysis of the randomized controlled EF-14 Trial (n=695). NCCN, ASCO and ESMO have developed tools to help inform physicians and policymakers about the clinical value of new cancer treatments in a standardized way. We report on the results of the tools for scoring the EF-14 trial data and comparatively discuss the results.
Materials/Methods: The EF-14 Trial proved the effect of adding TTFields to maintenance temozolomide (TMZ) for newly diagnosed glioblastoma patients. The ESMO Magnitude of Clinical Benefit Scale (MCBS) and the ASCO Net Health Benefit (NHB) frameworks calculate a score for the clinical value of a cancer treatment. We applied both classifications to the EF-14 trial data. Quality of life data from the EF-14 Trial was also published and is included in the scoring. NCCN self reports “evidence blocks” which are assessed by clinician panels and were recently published for the first line treatment of newly diagnosed GBM.
Results: Applying the ASCO framework to the EF-14 data resulted in a NHB score of 56. This scores is among the highest identified in the literature search. Applying the ESMO framework resulted in MCBS scores of A/5, these being the highest achievable scores for this framework. The ESMO framework valued the Health Related Quality of Life (HRQoL) gain during deterioration-free survival time with TTFields. The NCCN CNS panel designated TTFields as a category 1 recommendation in newly diagnosed GBM; the related NCCN evidence blocks support this recommendation.
Conclusions: While the frameworks used by ASCO and ESMO focus on different aspects and definition of clinical value both suggest that adding TTFields to maintenance TMZ for newly diagnosed glioblastoma patients provides patients with significant clinical benefits. The high ESMO and ASCO scores are reflecting the fact, that treatment with TTFields extended progression free and overall survival without additional systemic toxicities. The NCCN evidence blocks together with the NCCN category 1 recommendation strongly support the use of Optune in newly diagnosed GBM
Citation Format: Justin Kelly, Christina Proescholdt, Nicholas A. Blondin. Comparing clinical value scores (NCCN, ASCO and ESMO) for TTFields treatment in glioblastoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr LB-163.
Abstract LB-176: Transcriptome-wide association study revealed a novel gene associated with persistent hepatitis B virus infection among Chinese
Authors: Han Jing , Ni Jing , Zhu Meng , Fu Jin Guang , Hu Zhi Bin 
Published: August 2019

Abstract
The etiology of persistent hepatitis B virus (HBV) infection is complex and multifactorial, polygenic event with viral, environmental and genetic components being considered as the risk factors. Genome-wide association study (GWAS) has been applied into the exploration of genetic etiology of persistent hepatitis B virus infection among Chinese. However, the mechanisms beyond the genetic variants identified by GWAS located in noncoding regions are largely unknown. To further explore the causal gene of persistent hepatitis B virus (HBV) infection, we used a new approach developed by Gusev and Ko, leveraging expression imputation from large-scale GWAS data by using a small set of individuals with both genotype and gene expression data as a reference panel, to perform a transcriptome-wide association study (TWAS).Based on Genotype-Tissue Expression (GTEx) database, we included 97 individuals with both gene expression data in liver and SNP array data in blood as a reference panel. We first estimated the cis SNP heritability (cis-hg2) for each gene in 97 liver tissues using genome-wide complex trait analysis (GCTA) software, and kept cis-heritable genes for subsequent analysis. Then, we estimated the effect sizes of cis-SNPs on gene expression using genome-wide efficient mixed-model association (GEMMA) algorithm. Using the effect sizes trained from the reference panel, we imputed the gene expression levels for our existing NJMU HEP GWAS cohort (951 persistent hepatitis B virus (HBV) infection patients and 937 controls) and correlated the imputed gene expression values with persistent hepatitis B virus (HBV) infection trait. The cis-hg2 estimate was significantly nonzero for 2588 genes (P&lt;0.05). The average cis-hg2value was 0.438. Using GTEx database as a reference panel. In the training set, After FDR correction, we identified three potentially persistent hepatitis B virus (HBV) infection -associated genes, those genes were located in 6p21.3(HLA-DPA1,PTWAS=2.02×10-7), 3q21.1(PARP9, PTWAS=2.2×10-4) and 22q11.21 (TMEM191A, PTWAS= 3.8×10-4)respectively. 6p21.3 and 22q11.21 as our previous reported. 3q21.1 was a novel region.
Citation Format: Jing Han, Jing Ni, Meng Zhu, Jin Guang Fu, Zhi Bin Hu. Transcriptome-wide association study revealed a novel gene associated with persistent hepatitis B virus infection among Chinese [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr LB-176.
Abstract LB-180: Underreporting of race in genomic sequencing studies increases cancer health information disparities
Authors: Nugent Adrienne , Conatser Kelly R. , Turner Llaran L. , Nugent James T. , Sarino Esther May , Ricks-Santi Luisel J. 
Published: August 2019

Abstract
Purpose: Minorities are often underrepresented in clinical cancer research and the frequency of reporting of race in genomic sequencing studies of cancer is unknown. Disproportionate reporting of race can widen health information disparities and impair clinical decision-making in the underrepresented minority populations in whom cancer disease burden is greatest. This study determined the extent to which race is reported as a clinical variable in sequencing studies of cancer in the United States, the factors associated with reporting of race, and the participation rates of minority populations.
Methods: PubMed was systematically searched from January 1, 2010 through November 15, 2018 and a total of 9,410 non-duplicated studies were assessed for eligibility. Publications reporting whole genome or exome sequencing data for patients with one of the ten most common cancers in the United States at sufficient depth to identify rare variants were included in this study.
Results: 234 publications containing sequencing data from 16,358 unique patients met inclusion criteria. 36% of studies reported race as a clinical variable compared to 84% of studies reporting age and 83% of studies reporting gender. Reporting of race was associated with cancer type, cohort size, sequencing method, and tissue acquisition date. Minority populations were significantly underpowered to detect recurrent mutations in the majority of cancer types due to small sample size.
Conclusion: Race is underreported as a clinical variable in whole genome and exome sequencing studies of cancer in the United States. As the patient populations represented in research studies directly inform clinical decision-making and outcomes, substantially increased efforts are needed to sequence patients from underrepresented populations in order to reduce health disparities in patients of non-European ancestry.
Citation Format: Adrienne Nugent, Kelly R. Conatser, Llaran L. Turner, James T. Nugent, Esther May Sarino, Luisel J. Ricks-Santi. Underreporting of race in genomic sequencing studies increases cancer health information disparities [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr LB-180.