tbuckley/cabot-search huggingface dataset:
P-189 Role of radiomics in clinical prognostication and prediction of survival among a cohort of metastatic intrahepatic cholangiocarcinoma
Authors: V. Koyyala, A. Jajodia, A. Gupta, A. Chaturvedhi, A. Rao, S. Goyal, A. Mehta, H. Prosch, S. Pasricha, A. Choudhary, M. La Mantia, A. BP, N. Gupta, S. Singh
Journal: Annals of Oncology (2020)
P-244 Demographic data, risk factors, and clinical aspects of hepatocellular carcinoma (HCC) in Southeastern Europe during the last decade
Authors: E. Michalopoulou, E. Manthopoulou, D. Dimitroulopoulos, D. Kypreos, D. Katsinelos, I. Marakis, G. Sachtouris, X. Tsamakidis, K. Tsamakidis
Journal: Annals of Oncology (2020)
Soluble RARRES1 induces podocyte apoptosis to promote glomerular disease progression
Authors: Anqun Chen, Ye Feng, Han Lai, Wenjun Ju, Zhengzhe Li, Yu Li, Andrew Wang, Quan Hong, Fang Zhong, Chengguo Wei, Jia Fu, Tianjun Guan, Bichen Liu, Matthias Kretzler, Kyung Lee, John Cijiang He
Journal: Journal of Clinical Investigation (2020)

Using the Nephrotic Syndrome Study Network Consortium data set and other publicly available transcriptomic data sets, we identified retinoic acid receptor responder protein 1 (RARRES1) as a gene whose expression positively correlated with renal function decline in human glomerular disease. The glomerular expression of RARRES1, which is largely restricted to podocytes, increased in focal segmental glomerulosclerosis (FSGS) and diabetic kidney disease (DKD). TNF-α was a potent inducer of RARRES1 expression in cultured podocytes, and transcriptomic analysis showed the enrichment of cell death pathway genes with RARRES1 overexpression. The overexpression of RARRES1 indeed induced podocyte apoptosis in vitro. Notably, this effect was dependent on its cleavage in the extracellular domain, as the mutation of its cleavage site abolished the apoptotic effect. Mechanistically, the soluble RARRES1 was endocytosed and interacted with and inhibited RIO kinase 1 (RIOK1), resulting in p53 activation and podocyte apoptosis. In mice, podocyte-specific overexpression of RARRES1 resulted in marked glomerular injury and albuminuria, while the overexpression of RARRES1 cleavage mutant had no effect. Conversely, podocyte-specific knockdown of Rarres1 in mice ameliorated glomerular injury in the setting of adriamycin-induced nephropathy. Our study demonstrates an important role and the mechanism of RARRES1 in podocyte injury in glomerular disease.
Venous Thromboembolism Research Priorities: A Scientific Statement From the American Heart Association and the International Society on Thrombosis and Haemostasis
Authors: Mary Cushman, Geoffrey D. Barnes, Mark A. Creager, Jose A. Diaz, Peter K. Henke, Kellie R. Machlus, Marvin T. Nieman, Alisa S. Wolberg
Journal: Circulation (2020)

Venous thromboembolism is a major cause of morbidity and mortality. The impact of the US Surgeon General's The Surgeon General's Call to Action to Prevent Deep Vein Thrombosis and Pulmonary Embolism in 2008 has been lower than expected given the public health impact of this disease. This scientific statement highlights future research priorities in venous thromboembolism, developed by experts and a crowdsourcing survey across 16 scientific organizations. At the fundamental research level (T0), researchers need to identify pathobiological causative mechanisms for the 50% of patients with unprovoked venous thromboembolism and to better understand mechanisms that differentiate hemostasis from thrombosis. At the human level (T1), new methods for diagnosing, treating, and preventing venous thromboembolism will allow tailoring of diagnostic and therapeutic approaches to individuals. At the patient level (T2), research efforts are required to understand how foundational evidence impacts care of patients (eg, biomarkers). New treatments, such as catheter-based therapies, require further testing to identify which patients are most likely to experience benefit. At the practice level (T3), translating evidence into practice remains challenging. Areas of overuse and underuse will require evidence-based tools to improve care delivery. At the community and population level (T4), public awareness campaigns need thorough impact assessment. Large population-based cohort studies can elucidate the biological and environmental underpinnings of venous thromboembolism and its complications. To achieve these goals, funding agencies and training programs must support a new generation of scientists and clinicians who work in multidisciplinary teams to solve the pressing public health problem of venous thromboembolism.
SO-17 Association between tumor budding grade and T stage as prognostic value for recurrence with high-risk stage II colon cancer: A retrospective study
Authors: H. Kodama, T. Yamaguchi, N. Ishizuka, H. Yukami, M. Aoki, T. Miyamoto, T. Terazawa, T. Kii, M. Goto, H. Hamamoto, W. Osumi, M. Yamamoto, K. Tanaka, J. Okuda, K. Higuchi
Journal: Annals of Oncology (2020)
Downregulation of p53 by PKCϵ overexpression is associated with TRAIL resistance.
Authors: Eswar Shankar, Usha Sivaprasad, Alakananda Basu
Journal: Cancer Research (2007)

3600  Protein kinase C (PKC) is a family of phospholipid-dependent serine/threonine kinases that play an important role in cell proliferation and apoptosis. We have recently reported that PKCϵ is an anti-apoptotic protein that inhibits TRAIL-induced apoptosis in MCF-7 breast cancer cells. The p53 pathway has been shown to be an important regulator of TRAIL-induced apoptosis. In the present study, we examined the involvement of p53 in PKCϵ-mediated TRAIL resistance. We observed that PKCϵ overexpression in the MCF-7 cells (MCF-7/PKCϵ) was associated with a decrease in p53 at both the protein and mRNA level compared to vector-transfected control cells (MCF-7/Neo). Silencing p53 using siRNA abrogated TRAIL-induced cell death and caspase activation in MCF-7/Neo and MCF-7/PKCϵ cells. It has been shown that Akt regulates p53. Furthermore, we have previously shown that Akt acts downstream of PKCϵ and mediates survival of MCF-7/PKCϵ cells. Therefore, we determined the effect of Akt depletion on p53 levels. Knockdown of Akt in MCF-7/Neo and MCF-7/PKCϵ cells resulted in an increase in p53 level and enhanced cell death. These results demonstrate that PKCϵ may mediate TRAIL resistance via suppression of p53 expression in MCF-7 cells. (This work was supported by the grant CA71727 from the NCI.)
Abstract 11380: Pseudoexfoliative Glaucoma: The Role of Circulating Microparticles, Endothelial Dysfunction and Inflammation in the Progress of the Glaucomatous Disease
Authors: Evgenia Bourouki, Evangelos Oikonomou, Marilita Moschos, Gerasimos Siasos, Georgia Siasou, Nikolaos Gouliopoulos, Theodoros Paraskevopoulos, Nikolaos Papageorgiou, Antigoni Miliou, Efthimia Zacharia, Vasiliki Gennimata, Sotiris Tsalamandris, Dimitris Tousoulis
Journal: Circulation (2018)

Introduction: Pseudoexfoliative glaucoma (PEX) is a type of glaucoma characterized by the secretion of a grey-white, fibrogranular material in several tissues. Microparticles are shed membrane vesi...
Association of State-Level Opioid-Reduction Policies With Pediatric Opioid Poisoning
Authors: Michael S. Toce, Kenneth Michelson, Joel Hudgins, Michele M. Burns, Michael C. Monuteaux, Florence T. Bourgeois
Journal: JAMA Pediatrics (2020)

Opioid-reduction policies have been enacted by US states to address the opioid epidemic. Evidence of an association between policy implementation and decreased rates of pediatric opioid poisoning provides further justification for expanded implementation of these policies.
Mathematical Modeling Provides Evidence for Niche Competition in Human AML and Serves as a Tool to Improve Risk Stratification
Authors: Thomas Stiehl, Wenwen Wang, Christoph Lutz, Anna Marciniak-Czochra
Journal: Cancer Research (2020)

Abstract Acute myeloid leukemia (AML) is a stem cell–driven malignant disease. There is evidence that leukemic stem cells (LSC) interact with stem cell niches and outcompete hematopoietic stem cells (HSC). The impact of this interaction on the clinical course of the disease remains poorly understood. We developed and validated a mathematical model of stem cell competition in the human HSC niche. Model simulations predicted how processes in the stem cell niche affect the speed of disease progression. Combining the mathematical model with data of individual patients, we quantified the selective pressure LSCs exert on HSCs and demonstrated the model's prognostic significance. A novel model-based risk-stratification approach allowed extraction of prognostic information from counts of healthy and malignant cells at the time of diagnosis. This model's feasibility was demonstrable based on a cohort of patients with ALDH-rare AML and shows that the model-based risk stratification is an independent predictor of disease-free and overall survival. This proof-of-concept study shows how model-based interpretation of patient data can improve prognostic scoring and contribute to personalized medicine. Significance: Combining a novel mathematical model of the human hematopoietic stem cell niche with individual patient data enables quantification of properties of leukemic stem cells and improves risk stratification in acute myeloid leukemia.
Interacting hepatic PAI-1/tPA gene regulatory pathways influence impaired fibrinolysis severity in obesity
Authors: Ze Zheng, Keiko Nakamura, Shana Gershbaum, Xiaobo Wang, Sherry Thomas, Marc Bessler, Beth Schrope, Abraham Krikhely, Rui-Ming Liu, Lale Ozcan, José A. López, Ira Tabas
Journal: Journal of Clinical Investigation (2020)

Fibrinolysis is initiated by tissue-type plasminogen activator (tPA) and inhibited by plasminogen activator inhibitor 1 (PAI-1). In obese humans, plasma PAI-1 and tPA proteins are increased, but PAI-1 dominates, leading to reduced fibrinolysis and thrombosis. To understand tPA-PAI-1 regulation in obesity, we focused on hepatocytes, a functionally important source of tPA and PAI-1 that sense obesity-induced metabolic stress. We showed that obese mice, like humans, had reduced fibrinolysis and increased plasma PAI-1 and tPA, due largely to their increased hepatocyte expression. A decrease in the PAI-1 (SERPINE1) gene corepressor Rev-Erbα increased PAI-1, which then increased the tPA gene PLAT via a PAI-1/LRP1/PKA/p-CREB1 pathway. This pathway was partially counterbalanced by increased DACH1, a PLAT-negative regulator. We focused on the PAI-1/PLAT pathway, which mitigates the reduction in fibrinolysis in obesity. Thus, silencing hepatocyte PAI-1, CREB1, or tPA in obese mice lowered plasma tPA and further impaired fibrinolysis. The PAI-1/PLAT pathway was present in primary human hepatocytes, and associations among PAI-1, tPA, and PLAT in livers from obese and lean humans were consistent with these findings. Knowledge of PAI-1 and tPA regulation in hepatocytes in obesity may suggest therapeutic strategies for improving fibrinolysis and lowering the risk of thrombosis in this setting.
Interleukin-7 and interleukin-15 drive CD4+CD28null T lymphocyte expansion and function in patients with acute coronary syndrome
Authors: Jessica Bullenkamp, Veronica Mengoni, Satdip Kaur, Ismita Chhetri, Paraskevi Dimou, Zoë M J Astroulakis, Juan Carlos Kaski, Ingrid E Dumitriu
Journal: Cardiovascular Research (2020)

Inflammation has important roles in atherosclerosis. CD4+CD28null (CD28null) T cells are a specialized T lymphocyte subset that produce inflammatory cytokines and cytotoxic molecules. CD28null T cells expand preferentially in patients with acute coronary syndrome (ACS) rather than stable angina and are barely detectable in healthy subjects. Importantly, ACS patients with CD28null T-cell expansion have increased risk for recurrent acute coronary events and poor prognosis, compared to ACS patients in whom this cell subset does not expand. The mechanisms regulating CD28null T-cell expansion in ACS remain elusive. We therefore investigated the role of cytokines in CD28null T-cell expansion in ACS.High-purity sorted CD4+ T cells from ACS patients were treated with a panel of cytokines (TNF-α, IL-1β, IL-6, IL-7, and IL-15), and effects on the number, phenotype, and function of CD28null T cells were analysed and compared to the control counterpart CD28+ T-cell subset. IL-7- and IL-15-induced expansion of CD28null T cells from ACS patients, while inflammatory cytokines TNF-α, IL-1β, and IL-6 did not. The mechanisms underlying CD28null T-cell expansion by IL-7/IL-15 were preferential activation and proliferation of CD28null T cells compared to control CD28+ T cells. Additionally, IL-7/IL-15 markedly augmented CD28null T-cell cytotoxic function and interferon-γ production. Further mechanistic analyses revealed differences in baseline expression of component chains of IL-7/IL-15 receptors (CD127 and CD122) and increased baseline STAT5 phosphorylation in CD28null T cells from ACS patients compared to the control CD28+ T-cell subset. Notably, we demonstrate that CD28null T-cell expansion was significantly inhibited by Tofacitinib, a selective JAK1/JAK3 inhibitor that blocks IL-7/IL-15 signalling.Our novel data show that IL-7 and IL-15 drive the expansion and function of CD28null T cells from ACS patients suggesting that IL-7/IL-15 blockade may prevent expansion of these cells and improve patient outcomes.
P-4 The relationship between quality of life, adverse events, and treatment efficacy in treatment with first-line chemotherapy plus cetuximab for unresectable metastatic colorectal cancer: Results of phase II QUACK trial
Authors: O. Akira, S. Morita, S. Iwamoto, H. Hara, H. Tanioka, H. Satake, M. Kataoka, A. Tsuji, M. Ando, J. Sakamoto, K. Yamaguchi
Journal: Annals of Oncology (2020)
High microbiota reactivity of adult human intestinal IgA requires somatic mutations
Authors: Johanna Kabbert, Julia Benckert, Tim Rollenske, Thomas C.A. Hitch, Thomas Clavel, Vuk Cerovic, Hedda Wardemann, Oliver Pabst
Journal: The Journal of Experimental Medicine (2020)

The gut is home to the body’s largest population of plasma cells. In healthy individuals, IgA is the dominating isotype, whereas patients with inflammatory bowel disease also produce high concentrations of IgG. In the gut lumen, secretory IgA binds pathogens and toxins but also the microbiota. However, the antigen specificity of IgA and IgG for the microbiota and underlying mechanisms of antibody binding to bacteria are largely unknown. Here we show that microbiota binding is a defining property of human intestinal antibodies in both healthy and inflamed gut. Some bacterial taxa were commonly targeted by different monoclonal antibodies, whereas others selectively bound single antibodies. Interestingly, individual human monoclonal antibodies from both healthy and inflamed intestines bound phylogenetically unrelated bacterial species. This microbiota cross-species reactivity did not correlate with antibody polyreactivity but was crucially dependent on the accumulation of somatic mutations. Therefore, our data suggest that a system of affinity-matured, microbiota cross-species–reactive IgA is a common aspect of SIgA–microbiota interactions in the gut.
Targeting interleukin-4 to the arthritic joint
Authors: Valerie Spieler, Marie-Gabrielle Ludwig, Janet Dawson, Bruno Tigani, Amanda Littlewood-Evans, Caterina Safina, Hilmar Ebersbach, Klaus Seuwen, Martina Raschig, Björn ter Mors, Thomas D. Müller, Lorenz Meinel, Tessa Lühmann
Journal: Journal of Controlled Release (2020)
m6A modification-mediated BATF2 acts as a tumor suppressor in gastric cancer through inhibition of ERK signaling
Authors: Jian-Wei Xie, Xiao-Bo Huang, Qi-Yue Chen, Yu-Bin Ma, Ya-Jun Zhao, Li-Chao Liu, Jia-Bin Wang, Jian-Xian Lin, Jun Lu, Long-Long Cao, Mi Lin, Ru-Hong Tu, Chao-Hui Zheng, Chang-Ming Huang, Ping Li
Journal: Molecular Cancer (2020)

Abstract Background BATF2, also known as SARI, has been implicated in tumor progression. However, its role, underlying mechanisms, and prognostic significance in human gastric cancer (GC) are elusive. Methods We obtained GC tissues and corresponding normal tissues from 8 patients and identified BATF2 as a downregulated gene via RNA-seq. qRT-PCR and western blotting were applied to examine BATF2 levels in normal and GC tissues. The prognostic value of BATF2 was elucidated using tissue microarray and IHC analyses in two independent GC cohorts. The functional roles and mechanistic insights of BATF2 in GC growth and metastasis were evaluated in vitro and in vivo. Results BATF2 expression was significantly decreased in GC tissues at both the mRNA and protein level. Multivariate Cox regression analysis revealed that BATF2 was an independent prognostic factor and effective predictor in patients with GC. Low BATF2 expression was remarkably associated with peritoneal recurrence after curative gastrectomy. Moreover, elevated BATF2 expression effectively suppressed GC growth and metastasis in vitro and in vivo. Mechanistically, BATF2 binds to p53 and enhances its protein stability, thereby inhibiting the phosphorylation of ERK. Tissue microarray results indicated that the prognostic value of BATF2 was dependent on ERK activity. In addition, the N6-methyladenosine (m 6 A) modification of BATF2 mRNA by METTL3 repressed its expression in GC. Conclusions Collectively, our findings indicate the pivotal role of BATF2 in GC and highlight the regulatory function of the METTL3/BATF2/p53/ERK axis in modulating GC progression, which provides potential prognostic and therapeutic targets for GC treatment.
P-281 Colon cancer in elderly patients: Experience of the Medical Oncology Department of CHU Hassan II Fez
Authors: H. Erraichi, S. Berrad, L. Nouikh, K. Messoudi, L. Amaadour, K. Oualla, Z. Benbrahim, A. Samia, M. Nawfel
Journal: Annals of Oncology (2020)
Bcl-B expression in human epithelial and non-epithelial malignancies.
Authors: Maryla Krajewska, Jane Winter, Daina Variakojis, Alan Lichtenstein, Dayong Zhai, Michael Cuddy, Xianshu Huang, Frederic Luciano, Cheryl Baker, Hoguen Kim, Eunah Shin, Susan Kennedy, Allen Olson, Andrzej Badzio, Jacek Jassem, Ivo Meinhold-Heerlein, Michael Duffy, Aaron Schimmer, Ming Tsao, Ewan Brown, Dan Mercola, Stan Krajewski, John Reed
Journal: Cancer Research (2008)

2180  Purpose:Apoptosis plays an important role in neoplastic processes. Bcl-B is an anti-apoptotic Bcl-2 family member, which is known to change its phenotype upon binding to Nur77/TR3. The expression pattern of this protein in human malignancies has not been reported.  Experimental Design: We investigated Bcl-B expression in normal human tissues and several types of human epithelial and non-epithelial malignancy by immunohistochemistry and immunoblotting, correlating results with tumor stage, histologic grade, and patient survival.  Results: Bcl-B protein was strongly expressed in all normal plasma cells but found in only 18% of multiple myelomas (n = 133). Bcl-B immunostaining was also present in normal germinal center centroblasts and centrocytes, but follicular lymphomas (n =57) did not contain Bcl-B, while 52% of diffuse large B-cell lymphomas (DLBCLs) (n =48) were immunopositive. In breast (n=119), prostate (n=66), gastric (n=180), and colorectal (n=106) adenocarcinomas, as well as in non-small cell lung cancers (NSCLCs) (n=82), tumor-specific over-expression of Bcl-B was observed. Bcl-B expression was associated with parameters of poor prognosis, such as high tumor grade in breast cancer (p=0.009), microsatellite stability (p=0.0002) and left-sided anatomic location (p=0.02) of colorectal cancers, as well as with greater incidence of death from prostate cancer (p=0.005), and shorter survival and increased relative risk of death from small cell lung cancer (SCLC) (p=0.009). Conversely, although over-expressed in many gastric cancers, Bcl-B tended to correlate with better outcome (p=0.01) and more differentiated tumor histology (p
Yield of different approaches for screening for cardiovascular disease in asymptomatic diabetics
Authors: Timothy W Churchill, Carlos H Rassi, Carlos A Fernandes Tavares, Mateus G Fahel, Fabricia P Rassi, Augusto H Uchida, Bernardo L Wajchenberg, Antonio C Lerario, Edward Hulten, Márcio Sommer Bittencourt, Ron Blankstein
Journal: Circulation (2014)
Coronavirus Disease 2019 (COVID-19) and Cardiac Injury
Authors: Philippe Meyer, Jelena-Rima Ghadri, Christian Templin
Journal: JAMA Cardiology (2020)

Shaobo Shi, MD; Mu Qin, MD; Bo Shen, MD; Yuli Cai, MD; Tao Liu, MD; Fan Yang, MD; Wei Gong, MMSC; Xu Liu, MD, PhD; Jinjun Liang, MD, PhD; Qinyan Zhao, MD, PhD; He Huang, MD, PhD; Bo Yang, MD, PhD; Congxin Huang, MD, PhD
Multi-method genome- and epigenome-wide studies of inflammatory protein levels in healthy older adults
Authors: Robert F. Hillary, Daniel Trejo-Banos, Athanasios Kousathanas, Daniel L. McCartney, Sarah E. Harris, Anna J. Stevenson, Marion Patxot, Sven Erik Ojavee, Qian Zhang, David C. Liewald, Craig W. Ritchie, Kathryn L. Evans, Elliot M. Tucker-Drob, Naomi R. Wray, Allan F. McRae, Peter M. Visscher, Ian J. Deary, Matthew R. Robinson, Riccardo E. Marioni
Journal: Genome Medicine (2020)

The molecular factors which control circulating levels of inflammatory proteins are not well understood. Furthermore, association studies between molecular probes and human traits are often performed by linear model-based methods which may fail to account for complex structure and interrelationships within molecular datasets. In this study, we perform genome- and epigenome-wide association studies (GWAS/EWAS) on the levels of 70 plasma-derived inflammatory protein biomarkers in healthy older adults (Lothian Birth Cohort 1936; n = 876; Olink® inflammation panel). We employ a Bayesian framework (BayesR+) which can account for issues pertaining to data structure and unknown confounding variables (with sensitivity analyses using ordinary least squares- (OLS) and mixed model-based approaches). We identified 13 SNPs associated with 13 proteins (n = 1 SNP each) concordant across OLS and Bayesian methods. We identified 3 CpG sites spread across 3 proteins (n = 1 CpG each) that were concordant across OLS, mixed-model and Bayesian analyses. Tagged genetic variants accounted for up to 45% of variance in protein levels (for MCP2, 36% of variance alone attributable to 1 polymorphism). Methylation data accounted for up to 46% of variation in protein levels (for CXCL10). Up to 66% of variation in protein levels (for VEGFA) was explained using genetic and epigenetic data combined. We demonstrated putative causal relationships between CD6 and IL18R1 with inflammatory bowel disease and between IL12B and Crohn's disease. Our data may aid understanding of the molecular regulation of the circulating inflammatory proteome as well as causal relationships between inflammatory mediators and disease.
PD-2 Role of pretreatment SUVmax on 18F-FDG PET and clinicopathological features in the prognostic stratification of newly diagnosed intrahepatic cholangiocarcinoma
Authors: A. Rizzo, A. Ricci, G. Frega, A. Palloni, F. Dall'Olio, S. De Lorenzo, S. Tavolari, F. Abbati, F. Vasuri, M. Di Marco, N. Tober, M. Nigro, M. Mosca, V. Mollica, I. Maggio, F. Tovoli, M. Cescon, C. Serra, V. Ambrosini, C. Nanni, S. Fanti, G. Brandi
Journal: Annals of Oncology (2020)
Single-cell genomics reveals the genetic and molecular bases for escape from mutational epistasis in myeloid neoplasms
Authors: Justin Taylor, Xiaoli Mi, Khrystyna North, Moritz Binder, Alexander Penson, Terra Lasho, Katherine Knorr, Michael Haddadin, Bo Liu, Joseph Pangallo, Salima Benbarche, Daniel Wiseman, Ayalew Tefferi, Stephanie Halene, Yang Liang, Mrinal M. Patnaik, Robert K. Bradley, Omar Abdel-Wahab
Journal: Blood (2020)
P-57 Effectiveness and safety of trifluridine/tipiracil in patients with metastatic colorectal cancer in clinical practice in Poland
Authors: B. Radecka, M. Gełej, J. Streb, A. Siedlaczek, K. Kryka, P. Tokajuk, K. Winsko-Szczesnowicz, U. Czernek, M. Sobczak, M. Malik, L. Bodnar, M. Foszczynska-Kloda, K. Hetman, M. Wełnicka-Jaśkiewicz, K. Wierzbicka, M. Orlikowska, R. Becht, A. Deptala, B. Itrych, B. Kania-Zembaczynska
Journal: Annals of Oncology (2020)