bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 4660: Chronic obstructive pulmonary disease as an independent risk factor for cancer
Authors: Finkelstein Joseph , Huo Xingyue 
Published: September 2020

Abstract
Background: Low-grade systemic inflammation is considered a hallmark of chronic obstructive pulmonary disease (COPD) that potentially links COPD to increased cancer risk. However relationship between COPD and cancer remains controversial. The main purpose of this study was to assess the relationship between COPD and all-cause cancer among adult smokers in a nested case-control study.
Methods: The study used the 2018 Behavioral Risk Factor Surveillance System (BRFSS) dataset. Only individuals of 40 years and older who smoked at least 100 cigarettes in their lifetime were included into analysis. A nested case-control design has been employed with COPD as an exposure and cancer as an outcome. Cases with COPD were matched at 1:1 ratio with controls without COPD by age group, race, and sex using simple random sampling. Chi-square test was applied to determine whether the prevalence of cancer in the resulting groups was statistically significantly different. Conditional logistic regression was used to estimate the association between cancer and COPD after adjusting for covariates (education, income, BMI, marital, drinking and exercise status).
Results: Overall, 146,141 participants aged 40 or more who smoked at least 100 cigarettes in their entire lives were included into the study. 25,528 subjects with COPD were matched with non-COPD subjects by individual case-control matching at a 1:1 ratio. People who had COPD were more likely to report being diagnosed with cancer (OR=1.40, [95%CI, 1.32-1.48]) than non-COPD participants after adjusting for confounders. The result was similar in the original population (OR=1.39, [95%CI, 1.28-1.51]).
Conclusion: Our findings demonstrate that the diagnosis of COPD was significantly associated with cancer among smokers who aged more than 40 years old.
Citation Format: Joseph Finkelstein, Xingyue Huo. Chronic obstructive pulmonary disease as an independent risk factor for cancer [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 4660.
Abstract 4667: Associations between daily aspirin use and cancer risk across strata of major cancer risk factors in two large U.S. cohorts
Authors: Hurwitz Lauren M. , Michels Kara A. , Cook Michael B. , Pfeiffer Ruth M. , Trabert Britton 
Published: September 2020

Abstract
Purpose: Daily low-dose aspirin is recommended for certain individuals for prevention of cardiovascular disease and colorectal cancer. However, there are known risks associated with aspirin use. Identifying subgroups of individuals most likely to benefit from aspirin for cancer prevention would help to tailor risk-benefit calculations to maximize benefits and minimize risks. We investigated whether associations between daily aspirin use and risk of several cancers vary by other cancer risk factors, including age, body mass index (BMI), smoking status, physical inactivity, and family history of cancer.
Methods: We pooled 423,495 individuals from two prospective, U.S.-based studies: the NIH-AARP Diet and Health Study (1995-2011), a population-based cohort study, and the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (1993-2009), a multicenter randomized controlled trial. Daily aspirin use was self-reported at baseline and defined as use ≥5 days/week. Our main outcome measures were incident colorectal, ovarian, breast, endometrial, and aggressive prostate cancers. We used multivariable Cox proportional hazards regression to examine associations between daily aspirin use and risk of each cancer, overall and across strata of risk factors.
Results: Compared with non-use and non-daily use, daily aspirin use was associated with a 15% reduction in colorectal cancer risk (hazard ratio [HR]: 0.85, 95% confidence interval [CI]: 0.80-0.89). Risk reductions were generally consistent across strata of other risk factors but attenuated with increasing BMI (p-interaction=0.16). For ovarian cancer, there was no significant association overall (HR: 0.93, 95% CI: 0.80-1.08) but a reduced risk among obese women (HR: 0.73, 95% CI: 0.52-0.98, p-interaction=0.12). We observed suggestive modest risk reductions for breast (HR: 0.96, 95% CI: 0.91-1.00) and aggressive prostate (HR: 0.95, 95% CI: 0.90-1.00) cancer and a null association for endometrial cancer (HR: 0.96, 95% CI: 0.86-1.07), with no strong effect modification observed.
Conclusions: Daily aspirin use was associated with reduced colorectal cancer risk across strata of cancer risk factors. The magnitude of the benefit varied by BMI for colorectal cancer and was restricted to obese women for ovarian cancer. The potential modifying effect of BMI warrants further investigation and may need to be considered in risk-benefit calculations for aspirin use.
Citation Format: Lauren M. Hurwitz, Kara A. Michels, Michael B. Cook, Ruth M. Pfeiffer, Britton Trabert. Associations between daily aspirin use and cancer risk across strata of major cancer risk factors in two large U.S. cohorts [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 4667.
Abstract 4678: The role of EGR1 and AP1 in acute myeloid leukemia cell reprogramming toward cell cycle arrest and apoptosis
Authors: Roberts Michael , Kageler Lauren , Bendinelli Kayla , Bonner Shannon , Borah Ashir , Forrester Jeffrey 
Published: September 2020

Abstract
EGR and AP1 transcription factors are rapidly upregulated in acute myeloid leukemia cells responding to treatment with phorbol esters. Phorbol ester induced transcriptome changes are accompanied by phenotypic changes including cell cycle arrest, myeloid differentiation, and ultimately apoptosis. Here we present results documenting the transcriptome alterations of the phorbol ester response in HL-60 cells by DNA microarray and RNA-seq analyses, and explore the specific roles of EGR and AP1 in determining the evolving transcriptional program. Overexpression of egr1 or c-fos recapitulates many of the phorbol ester-induced transcriptome alterations and affects cell proliferation, differentiation and survival. Identification of changes in EGR1 and FOS/AP1 target gene expression supports the hypothesis that EGR and AP1 are involved in a genetic reprogramming of AML cells leading to loss of the leukemic phenotype and recovery of apoptotic competency. We also provide a comprehensive bioinformatic analysis of AML patient sample data provided by The Cancer Genome Atlas and the published study from Tyner et al., Nature 562:526-531 (2018) accessible through the Beat AML data viewer (Vizome) regarding expression of egr1. Egr1 high expression correlates with improved overall survival and a particular mutational signature distinct from patients with low egr1 expression. We define a mutational and transcriptional signature for AML patients based on egr1 expression levels that correlates with clinical outcomes.
Citation Format: Michael Roberts, Lauren Kageler, Kayla Bendinelli, Shannon Bonner, Ashir Borah, Jeffrey Forrester. The role of EGR1 and AP1 in acute myeloid leukemia cell reprogramming toward cell cycle arrest and apoptosis [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 4678.
Abstract 4688: Interaction of LEDGF/p75 with oncogenic transcription factors in docetaxel resistant prostate cancer cells
Authors: Hernandez Greisha L. Ortiz , Sanchez-Hernández Evelyn S. , Casiano Carlos A. 
Published: September 2020

Abstract
Prostate Cancer (PCa) progression leads to an advanced stage called metastatic castration PCa (mCRPC), for which currently there is no cure in spite of advances in treatment with new generation anti-androgen drugs and chemotherapy with taxanes such as docetaxel (DTX). Our group demonstrated previously that the stress oncoprotein Lens Epithelium Derived Growth Factor of 75 kD (LEDGF/p75) is upregulated in clinical prostate tumors and contributes to DTX-resistance in mCRPC cells. However, little is known about the molecular mechanisms by which LEDGF/p75 promotes taxane resistance. The C-terminus of LEDGF/p75 contains a domain called the Integrase Binding Domain (IBD), which in T cells is responsible for tethering the HIV-integrase complex to transcriptionally active chromatin. In non-PCa cells, the LEDGF/p75 IBD interacts with transcription complexes, such as Menin-MLL and the c-MYC binding protein JPO2, to promote cell survival. However, the relevance of these and others protein-protein interactions (PPIs) in the context of PCa chemoresistance has never been explored. This study was designed to test the hypothesis that interactions between LEDGF/p75, the c-MYC binding protein JPO2, Menin and MLL in DTX-resistant mCRPC cells contribute to chemoresistance. We demonstrated by immunoblotting a significant co-upregulation of JPO2, c-MYC, Menin, MLL, and LEDGF/p75 in the DTX-resistant PC3-DR and DU145-DR cell lines, compared to the parental, drug sensitive cells. We also observed nuclear co-localization of these proteins by immunofluorescence microscopy and confocal microscopy. Using an immunoprecipitation approach, we confirmed that endogenous JPO2, c-MYC, Menin, and MLL co-immunoprecipitate with LEDGF/p75 in the DTX-resistant PCa cell lines. We are extending these studies to other known interacting partners of LEDGF/p75 to determine if they are also upregulated in DTX-resistant PCa cells and interact with this protein in the chemoresistance context. In addition, we have initiated studies to evaluate the effects of pharmacologic and genetic inhibition of LEDGF/p75 and its interacting partners on sensitization of DR cells to DTX. We predict that targeting LEDGF/p75 PPIs will disrupt transcriptional activity contributing to DTX resistance. Our goals are to establish the contribution of these PPIs to LEDGF/p75-mediated transactivation of DTX resistance-associated genes, and target these interactions to overcome PCa chemoresistance.
Citation Format: Greisha L. Ortiz Hernandez, Evelyn S. Sanchez-Hernández, Carlos A. Casiano. Interaction of LEDGF/p75 with oncogenic transcription factors in docetaxel resistant prostate cancer cells [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 4688.
Abstract 4757: TNFAIP8 facilitates metabolic reprogramming in prostate cancer cells
Authors: Niture Suryakant , Lin Minghui , Odera Joab O. , Moore John , Kumar Deepak 
Published: September 2020

Abstract
Tumor necrosis factor-α-induced protein 8 (TNFAIP8), a member of TIPE/TNFAIP8 family, has been associated with multiple oncogenic roles in human cancers. Here we investigated the role of TNFAIP8 in metabolic reprogramming in prostate cancer (PCa) cells. Ectopic expression of TNFAIP8 increased cell survival/proliferation by enhancing metabolic activity in PCa cells. TNFAIP8 activated the PI3K-AKT pathway and up-regulated the expression of cell proliferation markers, cell cycle-related proteins, and PCa stem cell markers. TNFAIP8 was also found to regulate the expression of glucose metabolizing enzymes, enhancing glucose consumption, and endogenous ATP production. Treatment with glycolysis inhibitor 2-deoxyglucose (2-DG) reduced TNFAIP8 mediated glucose consumption /ATP production and spheroid formation in PCa cells. Moreover, TNFAIP8 maintained mitochondrial membrane potential and increased glycolysis/oxidative phosphorylation. These changes were also consistent with an observed altered metabolomic profile in PCa cells transfected with TNFAIP8. Collectedly, our data suggest that TNFAIP8 exerts its oncogenic effects by enhancing glucose metabolism and by facilitating metabolic reprogramming in PCa cells.
Citation Format: Suryakant Niture, Minghui Lin, Joab O. Odera, John Moore, Deepak Kumar. TNFAIP8 facilitates metabolic reprogramming in prostate cancer cells [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 4757.
Abstract 4814: Circular RNA expression in oral squamous cell carcinoma
Authors: Yang Hongyu , Wang Yufan 
Published: September 2020

Abstract
Objective: Circular RNA (circRNA) is a type of non-coding RNA molecule that affects the cellular regulatory network by sequestering microRNA (miRNA) like a sponge. This study was performed to identify differentially-expressed circRNA in oral squamous cell carcinomas (OSCCs). Methods: By using high-throughput transcriptome sequencing technology, we conducted a comprehensive study of circRNAs in human OSCC. The expression levels of circRNAs were determined by qRT-PCR and analyzed the correlations with clinicopathological characteristics in 42 patients. The circRNAs-miRNAs-mRNAs network was performed by bioinformatic integrated analysis.
Results: By high-throughput sequencing, microarray circRNA expression profiles were acquired from patients with OSCCs (n = 8) and controls (n = 8), which totaled 1921 existing circRNA molecules and 10021 novel circRNA molecules. Most of the circular RNA is from exons and distributed in the No. 1 and 2 chromosomes. Eight up-regulated and down-regulated circRNA molecules were identified as differentially-expressed in OSCCs. Among this, the expression of circ_000334, circ_006740, and circ_006371 are significantly down-regulated in 42 pairs of samples.
Conclusion: This study provides new insihgts into oncogenesis and development of OSCC, suggests novel therapeutic strategy for OSCC.
Citation Format: Hongyu Yang, Yufan Wang. Circular RNA expression in oral squamous cell carcinoma [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 4814.
Abstract 4818: miR-34-AGO-TNRC6A complex transcriptionally up-regulates BLU tumor suppressor via binding of a novel promoter-associated lncRNA in lung cancer
Authors: Ohno Shinichiro , Oikawa Keiki , Harada Yuichirou , Kuroda Masahiko 
Published: September 2020

Abstract
We focused on genes whose expression is induced by miR-34a, a potent tumor suppressor microRNA (miRNA) in lung cancer and many other types of cancer, and sought to elucidate the mechanisms underlying the tumor suppressor function of miR-34a. We found that the miR-34a inhibited the proliferation of lung cancer cells by inducing expression of the BLU(also known as ZMYND10) tumor suppressor. The next-generation sequencing analysis of RNA extracted from lung cancer tissues identified a novel divergent lncRNA expressed from promoter of BLUthat include two predicted miR-34 binding sites. Interestingly, miR-34a failed to induce the BLUtranscription in the mutants lacking these miR-34 binding sites in the lncRNA. In addition, the miR-34-AGO-TNRC6A complex induced transcription of BLUby binding to the lncRNA. This non-canonical miRNA pathway, which induces gene expression via cooperation between an miRNA and promoter-associated lncRNA, is a previously unknown tumor suppression mechanism of miR-34a.
Citation Format: Shinichiro Ohno, Keiki Oikawa, Yuichirou Harada, Masahiko Kuroda. miR-34-AGO-TNRC6A complex transcriptionally up-regulates BLU tumor suppressor via binding of a novel promoter-associated lncRNA in lung cancer [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 4818.
Abstract 4831: Stability of draw-time microRNA concentration in blood collection tubes
Authors: Seong Eunju , George Nicholas M. 
Published: September 2020

Abstract
Plasma microRNA, which is relatively abundant compared to other extracellular RNA species, has drawn attention for its potential implication as biomarkers of various disease conditions. However, the great donor-to-donor variability of specific microRNA levels has been a challenging factor in their further development as a diagnostic biomarker assay. Also widely recognized, the levels of specific microRNAs are sensitive to sample collection, storage and extraction methods. Upon blood draw, the plasma microRNAome undergoes changes in concentration as well as in composition, mostly due to the in vitro blood cell breakdown. In this study, using different blood collection tubes including EDTA and Streck RNA Complete BCT, we compared microRNA extraction from the full plasma vs from isolated plasma exosomes. For each sample, we measured microRNA concentrations by global fluorometric assays and by quantitative PCR for specific microRNAs. The Streck tube minimizes the in vitro changes of microRNAome, thus facilitating detection of rare microRNAs originating from a distant diseased tissue.
Citation Format: Eunju Seong, Nicholas M. George. Stability of draw-time microRNA concentration in blood collection tubes [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 4831.
Abstract 4852: CBLC functions as a novel therapeutic target to enhance the efficacy of paclitaxel on EGFR wild-type lung adenocarcinoma by downregulating AURKA
Authors: Hong Shiao-Ya , Kao Yu-Rung , Lin Yi-Ping , Lee Meng-Hsuan , Wu Jyun-Yi , Wu Cheng-Wen 
Published: September 2020

Abstract
Patients with lung adenocarcinoma harboring driver genes can be treated with target therapies, such as tyrosine kinase inhibitors for epithelial growth factor receptor (EGFR) mutations, anaplastic lymphoma kinase (ALK) inhibitors for ALK gene rearrangements, and so on. However, a large portion of lung adenocarcinoma patients, especially for those with wild-type EGFR, still do not have valid target therapies in clinics. The CBL family proteins (CBL, CBLB, and CBLC) are E3 ubiquitin ligases of protein tyrosine kinases (PTKs), including EGFR, hepatocyte growth factor receptor (MET), and SRC proto-oncogene (SRC). It has been reported that the K63-linkaged ubiquitination mediated by CBL can negatively regulate activated EGFR (aEGFR) signaling through lysosomal degradation. Previously, we discovered that CBLC, unlike CBL, possesses an oncogenic function and positively regulates aEGFR stability through polyubiquitination via K6 and K11 linkages. The CBLC-mediated conjugation of polyubiquitin promotes aEGFR preferentially recycled back to the plasma membrane, or trafficked to the cell nucleus, leading to the sustained activation of EGFR signaling in lung adenocarcinoma. Aside from aEGFR dysregulation, we recently found that CBLC assumes a novel role in positively regulating the expression of Aurora kinase A (AURKA), which contributes to tumor development by promoting cell proliferation, metastasis, epithelial-mesenchymal transition, and drug resistance. In lung adenocarcinoma cells with wild-type EGFR, CBLC knockdown significantly reduced cell viability, delayed cell cycle progression and increased apoptotic death. Our study also showed that CBLC knockdown in EGFR wild type cells was associated with increased sensitivity to paclitaxel, probably through downregulating AURKA. Taken together, these findings indicated that CBLC may play a role in promoting cell cycle progression and may be a novel therapeutic target to enhance the efficacy of paclitaxel on EGFR wild-type lung adenocarcinoma.
Citation Format: Shiao-Ya Hong, Yu-Rung Kao, Yi-Ping Lin, Meng-Hsuan Lee, Jyun-Yi Wu, Cheng-Wen Wu. CBLC functions as a novel therapeutic target to enhance the efficacy of paclitaxel on EGFR wild-type lung adenocarcinoma by downregulating AURKA [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 4852.
Abstract 488: Establishing consistent methods for the generation of donor-derived iPSCs from T cell subsets
Authors: Landon Mark , MacArthur Chad C. , Hernandez Melissa E. , Lakshmipathy Uma , Guzman Jerry 
Published: September 2020

Abstract
T cell-based immunotherapies offer a potent and specific solution to grievous diseases such as cancer and viral infections. Expansion and re-infusion of antigen specific T cells has seen success in the treatment of metastatic melanoma and prevention of viral infections such as CMV and EBV. Additionally, engineered T cell therapies, especially chimeric antigen receptor (CAR) T cells, have been met with great clinical success and spurred innovation within the field of cellular immunotherapies. While promising, these therapies rely on sourcing T cells from donor derived blood. This process is invasive to the patient, especially when multiple or prolonged blood draws are required to obtain sufficient T cell numbers. Additionally, T cells sourced from diseased patients are often exhausted and display significantly perturbed growth and dysfunctional responses to antigen stimulation. An appealing alternative is somatic reprogramming of T cells to generate induced pluripotent stem cells (iPSCs) and differentiated into rejuvenated T cells that retain the original TCR, particularly with tumor infiltrating lymphocytes or viral specific T cells. We had previously reported a Sendai-virus based CytoTune 2.1 Reprogramming specifically designed for translational and clinical research. In this study we examine the effect of various cellular phenotypes and optimize methods for consistent reprogramming of multiple donor T cell reprogramming. Additionally, pan CD3+ cells isolated using different methods and further enriched for CD4+ and CD8+ were successfully reprogrammed. The resulting iPSCs were extensively characterized to ensure that pluripotency was achieved and that TCR sequences were preserved. This approach of reprogramming T cells and specific cell subtypes to derive iPSC with a known TCR sequence enables their use for downstream application as a renewable source of T cells with known antigen specificity.
Citation Format: Mark Landon, Chad C. MacArthur, Melissa E. Hernandez, Uma Lakshmipathy, Jerry Guzman. Establishing consistent methods for the generation of donor-derived iPSCs from T cell subsets [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 488.