tbuckley/cabot-search huggingface dataset:
Abstract 3288: The landscape of circular RNA in cancer
Authors: Josh N. Vo, Yajia Zhang, Sudhanshu Shukla, Lanbo Xiao, Dan Robinson, Yi-Mi Wu, Sisi Gao, Carl Engelke, Xuhong Cao, Alexey Nesvizhskii, Arul Chinnaiyan
Journal: Cancer Research (2018)

Abstract Circular RNAs (circRNAs) are an intriguing class of RNA due to their covalently closed structure, relatively high stability, and implicated roles in gene regulation. Here we used exome capture RNA-Seq, a non-poly(A) high-throughput RNA-sequencing protocol, to detect and characterize circRNAs across &amp;gt;800 cancer samples. When compared against the two gold-standard methods (Ribo-Zero and RNase-R), capture sequencing significantly enhanced the enrichment of circRNAs and preserved accurate circular-to-linear ratios. We compiled the detected circRNAs from capture sequencing into the public OncoCirc database, the most comprehensive catalogue of circRNA species to-date. With this database, we identified the best circRNAs to serve as biomarkers for prostate cancer and were able to detect a novel class of circRNAs involved two genes. OncoCirc will serve as a valuable resource for the development of circRNA for diagnostic or therapeutic purposes for other cancers, as well as the study of circularization as an intriguing RNA splicing process. Citation Format: Josh N. Vo, Yajia Zhang, Sudhanshu Shukla, Lanbo Xiao, Dan Robinson, Yi-Mi Wu, Sisi Gao, Carl Engelke, Xuhong Cao, Alexey Nesvizhskii, Arul Chinnaiyan. The landscape of circular RNA in cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3288.
Dietary Diversity: Implications for Obesity Prevention in Adult Populations: A Science Advisory From the American Heart Association
Authors: Marcia C. de Oliveira Otto, Cheryl A.M. Anderson, Jennifer L. Dearborn, Erin P. Ferranti, Dariush Mozaffarian, Goutham Rao, Judith Wylie-Rosett, Alice H. Lichtenstein
Journal: Circulation (2018)

“Eat a variety of foods,” or dietary diversity, is a widely accepted recommendation to promote a healthy, nutritionally adequate diet and to reduce the risk of major chronic diseases. However, recent evidence from observational studies suggests that greater dietary diversity is associated with suboptimal eating patterns, that is, higher intakes of processed foods, refined grains, and sugar-sweetened beverages and lower intakes of minimally processed foods, such as fish, fruits, and vegetables, and may be associated with weight gain and obesity in adult populations. This American Heart Association science advisory summarizes definitions for dietary diversity and reviews current evidence on its relationship with obesity outcomes, eating behavior, and food-based diet quality measures. Current data do not support greater dietary diversity as an effective strategy to promote healthy eating patterns and healthy body weight. Given the current state of the science on dietary diversity and the insufficient data to inform recommendations on specific aspects of dietary diversity that may be beneficial or detrimental to healthy weight, it is appropriate to promote a healthy eating pattern that emphasizes adequate intake of plant foods, protein sources, low-fat dairy products, vegetable oils, and nuts and limits consumption of sweets, sugar-sweetened beverages, and red meats.
Abstract LB-070: Design and modular development of I-PARTS: An integrated platform for anti-cancer radiation therapeutics screening
Authors: Rao V. Papineni, Sylvain Costes, Shayoni Ray, William McLaughlin, Brendan Lukaniec, Kurt Kruger, Keith Kanugi
Journal: Cancer Research (2018)

Abstract Tumor irradiation during cancer treatment induces cell death by apoptosis, mitotic death, and clonogenic death. With expanded global access to cancer radiotherapy, there is a need to discover agents with anti-cancer and radiation sensitizing properties. in vitro high-throughput screening (HTS) systems routinely used to screen agents for cytotoxicity assays unfortunately do not directly measure clonogenic potential and fail to accurately predict the efficacy of an agent either in subsequent preclinical animal model testing or in clinical trials. Clonogenic assays unlike colorimetric and metabolic assays for determining cell viability and apoptosis, are less susceptible to artifacts. We are addressing these requirements through an integrated I-PARTS platform development and optimization. Here, the design and the prototype of a fully enclosed imaging/X-ray irradiation system will be presented. The proof of principle experimentation to obtain high content information on the cellular response to specific primary human cells (normal or tumors) to a variety of radiation doses and fraction modality will be described. The initial approaches taken towards the establishment of an integrated platform to screen anti-cancer drugs will be discussed. Citation Format: Rao V. Papineni, Sylvain Costes, Shayoni Ray, William McLaughlin, Brendan Lukaniec, Kurt Kruger, Keith Kanugi. Design and modular development of I-PARTS: An integrated platform for anti-cancer radiation therapeutics screening [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr LB-070.
Abstract 12703: Antiepileptic Medicines is Associated With Brugada-Type ST Elevation in Patients With Epilepsy
Authors: NaruyaIshizue, ShinichiNiwano, MasanoriSaitou, TazuruIgarashi, TamamiFujiishi, TomoharuYoshizawa, JunKishihara, MasamiMurakami, HidehiraFukaya, HiroeNiwano, HitoshiMiyaoka, JunyaAko
Journal: Circulation (2014)

Purpose: Some of psychotropic medicines are known to cause ECG changes such as QT prolongation. Because some of antiepileptic medicines have sodium or calcium channel blocking effects, they may lead to manifestation of Brugada-type ST elevation or J-wave like inter-ventricular conduction delay. In the present study, we focused on the patients with epilepsy who have continued to take antiepileptic medicines, and the prevalence of Brugada-type ST elevation was evaluated in their ECG. Method: The study population consisted of 120 consecutive patients with epilepsy who have continued to take more than one of antiepileptic medicines (carbamazepine 63, phenytoin 43, valproic acid 50, phenobarbital 10 and the others 23 patients) and have analyzable ECG recordings during these therapies. Brugada-type ST elevation was classified into type 1-3 in accordance with the consensus report of Brugada syndrome. Results: Out of 120 patients, 15 (12.5%) exhibited Brugada-type ST elevation (type 1 6.67%, type2 20.0%, and type...
Abstract 4043: A novel role for Hedgehog signaling in macrophage-mediated immune evasion
Authors: Ann Hanna, Dongquan Chen, Darshan S. Chandrashekar, Sooryanarayana Varambally, Rajeev S. Samant, Lalita A. Shevde
Journal: Cancer Research (2018)

Abstract In the tumor microenvironment, breast cancer cells participate in crosstalk with the surrounding stroma. This tumor-stromal interaction forms a balance that dictates tumor suppressing or promoting response mechanisms. Macrophages in the tumor microenvironment are plastic and can mediate several functions depending on their activation states. Tumor-associated macrophages co-exist as two major phenotypes: anti-tumorigenic and immune-eliciting classically activated M1 as well as tumor-promoting and immune-suppressive alternatively activated M2 macrophages. Alternatively activated macrophages are associated with more aggressive stages and poor clinical outcomes in breast cancer patients as they suppress the tumoricidal properties of the immune system, thus facilitating tumor cell proliferation and dissemination. Hedgehog (Hh) signaling is a critical developmental pathway; its activation modulates vital cellular processes such as cell proliferation, stem-cell differentiation, and angiogenesis. While the Hh signaling pathway is normally tightly controlled, it can often be dysregulated which fosters tumorigenesis and tumor progression. Aberrant Hh signaling activation is particularly implicated in breast cancer progression and metastasis. In this study, we investigate the role of Hh signaling in polarizing breast cancer-associated macrophages toward the detrimental M2 subtype. We report that targeting different steps of the Hh signaling cascade attenuates the cytokine profile associated with M2 macrophages. Additionally, we demonstrate that Hh signaling enables the molecular mechanism responsible for alternative macrophage polarization. We furthermore identify significant shifts in immune cell populations infiltrating the primary tumor when we administer an FDA-approved Hh inhibitor to an in vivo mammary tumor model. This altered immune profile is dynamically characterized by a reduction in immune-suppressive cells concomitant with enhanced antigen presentation properties and cytotoxic immune cell infiltration, overall culminating in reduced metastasis. Thus, we describe a novel role for Hh signaling in enabling pro-tumorigenic immunity by alternatively polarizing breast cancer-associated macrophages. This study identifies a novel strategy, which has potential clinical implications to treat breast cancer through targeting aberrant tumor cell Hh activation and eliciting a robust anti-tumorigenic immune response. Citation Format: Ann Hanna, Dongquan Chen, Darshan S. Chandrashekar, Sooryanarayana Varambally, Rajeev S. Samant, Lalita A. Shevde. A novel role for Hedgehog signaling in macrophage-mediated immune evasion [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4043.
Abstract 17662: Association of Lipid Core Plaque as Detected by Coronary Near-infrared Spectroscopy With Short- and Long-term Outcomes After Cardiac Catheterization
Authors: Eric Fuh, Vishal G Patel, Owen N Mogabgab, Subhash Banerjee, Emmanouil S Brilakis
Journal: Circulation (2013)

Background: We examined the association of lipid core plaque (LCP) as detected by intracoronary near-infrared spectroscopy (NIRS) with short- and long-term clinical outcomes after coronary angiography and percutaneous coronary intervention (PCI). Methods: Between 2009 and 2012 coronary NIRS was performed in 185 coronary arteries in 162 patients who underwent clinically-indicated cardiac catheterization. PCI was performed in 132 coronary arteries. LCP was defined as at least 2 contiguous yellow blocks on the block chemogram. The association of LCP with short and long-term outcomes was evaluated. Short term major adverse cardiac events (MACE) included peri-procedural myocardial infarction (MI), stroke, death, stent thrombosis and no reflow. Long-term MACE included all-cause mortality, stroke, re-hospitalization for acute coronary syndrome (ACS), MI, target vessel revascularization and target lesion revascularization. Results: Mean age was 62 ± 8 years and most patients (98%) were men. Most patients presente...
Abstract 595: Perioperative risk factors for postoperative pneumonia after major oral cancer surgery: A retrospective analysis of 331 cases
Authors: Jieyun Xu, Pei Yu, Weiwang Wang, Zehang Zhuang, Xiqiang Liu
Journal: Cancer Research (2018)

Abstract Objective: Postoperative pneumonia (POP) is common and results in prolonged hospital stays, higher costs, increased morbidity and mortality. However, data on the incidence and risk factors of POP after oral and maxillofacial surgery are rare. This study aims to identify perioperative risk factors for POP after major oral cancer (OC) surgery. Methods: Perioperative data and patient records of 331 consecutive subjects were analyzed in the period of April 2014 to March 2016. We individually traced each OC patient for a period to discharge from the hospital or 45 days after surgery, whichever occur later. Results: The incidence of POP after major OC surgery with free flap construction or major OC surgery was 11.6% or 4.5%, respectively. Patient-related risk factors for POP were male sex, T stage, N stage, clinical stage and preoperative serum albumin level. Among the investigated procedure-related variables, incision grade, mandibulectomy, free flap reconstruction, tracheotomy, intraoperative blood loss, and the length of the operation were shown to be associated with the development of POP. Postoperative hospital stay was also significantly related to increased incidence of POP. Using a multivariable logistic regression model, we identified male sex, preoperative serum albumin level, operation time and postoperative hospital stay as independent risk factors for POP. Conclusion: Several perioperative risk factors can be identified that are associated with POP. At-risk oral cancer patients should be subjected to intensified postoperative pulmonary care. Citation Format: Jieyun Xu, Pei Yu, Weiwang Wang, Zehang Zhuang, Xiqiang Liu. Perioperative risk factors for postoperative pneumonia after major oral cancer surgery: A retrospective analysis of 331 cases [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 595.
Abstract 2238: Self-microemulsifying drug delivery systems (SMEDDS) containing novel compounds for the chemoprevention of pancreatic cancer
Authors: Preshita Desai, Arvind Thakkar, Jeffrey Wang, Sunil Prabhu
Journal: Cancer Research (2018)

Abstract Pancreatic cancer (PC) is the fourth leading cause of deaths in the United States, claiming approximately 43,000 lives every year. Existing trends suggest that it will be the second cause of death after lung cancer within the next 20 years. With mortality rates remaining high even after decades of research, scientists are now turning to develop chemopreventive strategies that may stop or delay the initiation and progression of the disease. Our study reports the chemoprevention potential of (1) a free drug combination of H1-receptor antagonist drug with Sulforaphane (SFN), a neutraceutical compound derived from broccoli and (2) lipid nanocarriers of H1-receptor antagonist drug (SP1 SMEDDS; formulation patent pending) with free SFN when administered at low doses in human pancreatic cancer cell lines (MIA PaCa-2 and Panc-1). IC50 concentrations were calculated for various treatment groups using MTS viability assay in accordance with published protocol, using 96-well microplates and incubation time of 72 h. The free drug combination revealed almost 70-fold and 20-fold enhancement in chemoprevention efficacy (based decrease in cancer cell viability) as compared to controls. Interestingly, the free drug combination (at 5µM) showed ~55 % (p&amp;lt;0.001) inhibition in cell lines whereas no measurable response was observed with individual free drug treatments at the same concentration. This confirmed the synergistic chemoprevention potential of the free drug combination. SP1 SMEDDS were optimized for particle size, encapsulation efficiency and chemoprevention efficacy. SP1 SMEDDS (10µM) by itself exhibited 54% (p&amp;lt;0.001) cell line inhibition whereas no measurable response was observed with free drug at that same concentration, confirming the potential of lipid nanocarriers in enhancing the chemoprevention activity. Moreover, the SP1 SMEDDS in combination with free SFN demonstrated synergistic activity with 500-fold, 140-fold and 7-fold enhancement in chemoprevention potential as compared to the free HI-receptor antagonist, SFN and the free drug combination, respectively. In conclusion, a novel lipid formulation of an H1-receptor antagonist in combination with free SFN was invented (provisional patent applied) to successfully elicit PC chemoprevention. Future studies will look into the efficacy of this novel formulation in in vivo PC models. Citation Format: Preshita Desai, Arvind Thakkar, Jeffrey Wang, Sunil Prabhu. Self-microemulsifying drug delivery systems (SMEDDS) containing novel compounds for the chemoprevention of pancreatic cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2238.
Unusual Manifestation of Libman-Sacks Endocarditis in Systemic Lupus Erythematosus
Authors: CarstenSchneider, EddaBahlmann, MatthiasAntz, RudolphBauer, JacobusReimers, WernerRaut, ChristianBusch, FrankRathjen, RolandMoll, Karl-HeinzKuck
Journal: Circulation (2003)
Abstract 5582: Use of circulating tumor DNA (ctDNA) to predict superiority of dosing schedules in early clinical development
Authors: Juliann Chmielecki, Zhongwu Lai, Kristy Potts, Kavita Garg, Mark Li, J Carl Barrett
Journal: Cancer Research (2018)

Abstract Changes in ctDNA can be used as a surrogate molecular marker of response to determine clinical efficacy and often precede imaging changes. This analysis is valuable to early clinical trials for dose optimization as response data may not be available for patients because of the short period of time on drug. Unlike other ctDNA applications where tumor-specific single gene mutations are followed over time, inclusion of “all comers” populations in phase I trials necessitates a comprehensive assay design optimized to detect multiple ctDNA changes from diverse tumors. Therefore, we developed a highly sensitive bespoke ctDNA panel (Resolution Bioscience) suitable for monitoring applications in “all comers” solid tumor populations. The panel uses next-generation sequencing technology to interrogate mutational hotspots from 8 oncogenes as well as the complete coding sequences of 3 tumor suppressor genes. Validation studies established the mutant allele frequency (MAF) limit of detection for short variants and small insertions/deletions as 0.1%; additionally, mutant alleles detected at or above this frequency can be followed below this threshold in serial samples. The assay requires 2mL plasma and results are reported within 14 days. In silico analysis predicted detection of at least one monitorable somatic alteration from ~63% of solid tumors that shed ctDNA. To demonstrate applicability, we used this assay to analyze serial ctDNA samples from patients enrolled in dose-escalation cohorts for the Wee1 inhibitor, AZD1775 (NCT02610075). Dosing schedules were compared for the degree of ctDNA clearance after completion of the first cycle, and correlated with subsequent RECIST response data, where available. To date, 15 patients were evaluable, with more anticipated as additional cohorts accrue. Greater ctDNA decreases were observed with higher drug dose, and longer drug exposure. Together with safety and exposure data, our studies demonstrate that ctDNA dynamics can be used to inform decisions around optimal dosing schedule. This enables rapid decision making before imaging studies are available, and complements traditional measurements of target engagement. Citation Format: Juliann Chmielecki, Zhongwu Lai, Kristy Potts, Kavita Garg, Mark Li, J Carl Barrett. Use of circulating tumor DNA (ctDNA) to predict superiority of dosing schedules in early clinical development [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5582.
COP9 Signalosome Controls the Degradation of Cytosolic Misfolded Proteins and Protects Against Cardiac Proteotoxicity
Authors: HuaboSu, JieLi, HanmingZhang, WenxiaMa, NingWei, JinbaoLiu, XuejunWang
Journal: Circulation Research (2015)

Rationale:Impaired degradation of misfolded proteins is associated with a large subset of heart diseases. Misfolded proteins are degraded primarily by the ubiquitin-proteasome system, but the ubiquitin ligases responsible for the degradation remain largely unidentified. The cullin deneddylation activity of the COP9 signalosome (CSN) requires all 8 CSN subunits (CSN1 through CSN8) and regulates cullin-RING ligases, thereby controlling ubiquitination of a large number of proteins; however, neither CSN nor cullin-RING ligases is known to regulate the degradation of cytosolic misfolded proteins. Objective:We sought to investigate the role of CSN8/CSN in misfolded protein degradation and cardiac proteinopathy. Methods and Results:Cardiac CSN8 knockout causes mouse premature death; hence, CSN8 hypomorphism (CSN8hypo) mice were used. Myocardial neddylated forms of cullins were markedly increased, and myocardial capacity of degrading a surrogate misfolded protein was significantly reduced by CSN8 hypomorphism. Wh...
Abstract 1587: Detection of PD-L1 and PD-1 positive circulating tumor cells (CTCs) in non-small cell lung cancer (NSCLC) patients treated with nivolumab
Authors: Galatea Kallergi, Anastasios Koutsopoulos, Eleni Lagoudaki, Despoina Agouraki, Eleni-Kiriaki Vetsika, Anastasia Voumvouraki, Stuart S. Martin, Filippos Koinis, Christos Stournaras, Vassilis Georgoulias, Athanasios Kotsakis
Journal: Cancer Research (2018)

Abstract Introduction: Circulating tumor cells (CTCs) are considered as a “liquid biopsy” that allows the assessment of tumor changes over time. Tumor cells may escape from the immune system through the activation of PD-1/PD-L1 axis. Targeting these molecules with monoclonal antibodies has shown encouraging results at many types of cancers, including NSCLC. In the current study we investigated the expression of PD-1/PD-L1 molecules on the CTCs isolated from NSCLC patients treated with Nivolumab. Methods: CTCs were isolated based on their size using the ISET platform from 27 patients before treatment, after 1 cycle and 3 cycles. CTCs were detected with Giemsa staining and immunofluorescence (IF) experiments, using either pancytokeratin (A45-B/B3) (CK7)/PD-1/CD45 or (A45-B/B3)(CK7)/PD-L1/CD45 combination of antibodies and analysis with the ARIOL system. Spiking experiments using the NSCLC cell lines: H460, H1299, HCC827 and SKMES in normal blood were used to evaluate the detection method. Results: Giemsa evaluation in Nivolumab-treated patients at baseline (25 evaluable samples), after the 1st (9 evaluable samples) and the 3rd (8 evaluable patients) cycle of treatment showed that CTCs could be detected in 48% (12/25), 33.3% (3/9) and 50% (4/8) of patients, respectively. IF could also reveal the presence of CK-positive cells in 44.4% (12/27), 22% (2/9) and 75% (6/8) patients, respectively. PD-1 (+) CTCs were detected in 33.3% (4/12) of patients at baseline, in, 0% after the 1 and 16.7% (1/6) of patients after the 3rd cycle. The same percentages were identified for PD-L1 expression in the same cohort of patients. The expression of PD-1 at baseline was associated with poorer OS (p=0.022) and PFS (p=0.011), while the expression of PD-L1 was associated with shorter PFS (p=0.011). Multivariate analysis revealed that the presence of CK-positive cells is an independent prognostic factor for OS (p=0.028) Conclusion: Nivolumab reduced the number of PD-1- and PD-L1-expressing CTCs in advanced NSCLC patients. Furthermore the expression of both markers at baseline is associated with the clinical outcome. Citation Format: Galatea Kallergi, Anastasios Koutsopoulos, Eleni Lagoudaki, Despoina Agouraki, Eleni-Kiriaki Vetsika, Anastasia Voumvouraki, Stuart S. Martin, Filippos Koinis, Christos Stournaras, Vassilis Georgoulias, Athanasios Kotsakis. Detection of PD-L1 and PD-1 positive circulating tumor cells (CTCs) in non-small cell lung cancer (NSCLC) patients treated with nivolumab [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1587.