tbuckley/cabot-search huggingface dataset:
Abstract IA-007: The KPC model has helped advance pancreatic cancer therapy: Agree
Authors: Kenneth P. Olive
Journal: Cancer Research (2021)

Abstract The KPC genetically engineered mouse has been widely utilized within the pancreatic cancer field as a preclinical model system that recapitulates many aspects of human pancreatic ductal adenocarcinoma. The model has proven particularly accurate in replicating many of the etiological, histopathological, and physiological features of the human disease. KPC mouse pancreatic tumors also exhibit the broad chemoresistance phenotype that characterizes human pancreatic cancer, proving to be uniquely resistant to a wide range of cytotoxic, targeted, and immuno-oncology drugs. Nevertheless, the lack of efficacy in several clinical trials that derived from studies initially performed in the KPC model has provoked questions about the clinical predictiveness of the model, and by extension, its preclinical utility. This presentation will summarize the history and lessons learned from using the KPC mouse model and highlight impacts the model has had on pancreatic cancer therapy. We will focus in particular on the appropriate interpretation of preclinical results and understanding the similarities and differences between corresponding trials performed in KPC mice and humans. To date, the model has proven successful both in advancing promising biology-based regimens to the clinic and of dissuading the further clinical development of ineffective regimens. Moreover, by providing a vehicle for the conduct of “post-clinical” trials, the KPC model has enabled the study and understanding of why pancreatic cancer trials can fail, leading to critical lessons that are informing the design of future clinical trials (and the prioritization of candidate therapeutic agents). Innovative and promising therapeutics approaches developed from studies in the KPC model continue to advance through clinical trials and are bolstered by ongoing co-clinical efforts that iteratively pass from human to mouse and back again. Citation Format: Kenneth P. Olive. The KPC model has helped advance pancreatic cancer therapy: Agree [abstract]. In: Proceedings of the AACR Virtual Special Conference on Pancreatic Cancer; 2021 Sep 29-30. Philadelphia (PA): AACR; Cancer Res 2021;81(22 Suppl):Abstract nr IA-007.
Supplying the trip to antibody production—nutrients, signaling, and the programming of cellular metabolism in the mature B lineage
Authors: Mark R. Boothby, Shawna K. Brookens, Ariel L. Raybuck, Sung Hoon Cho
Journal: Cellular and Molecular Immunology (2021)

The COVID pandemic has refreshed and expanded recognition of the vital role that sustained antibody (Ab) secretion plays in our immune defenses against microbes and of the importance of vaccines that elicit Ab protection against infection. With this backdrop, it is especially timely to review aspects of the molecular programming that govern how the cells that secrete Abs arise, persist, and meet the challenge of secreting vast amounts of these glycoproteins. Whereas plasmablasts and plasma cells (PCs) are the primary sources of secreted Abs, the process leading to the existence of these cell types starts with naive B lymphocytes that proliferate and differentiate toward several potential fates. At each step, cells reside in specific microenvironments in which they not only receive signals from cytokines and other cell surface receptors but also draw on the interstitium for nutrients. Nutrients in turn influence flux through intermediary metabolism and sensor enzymes that regulate gene transcription, translation, and metabolism. This review will focus on nutrient supply and how sensor mechanisms influence distinct cellular stages that lead to PCs and their adaptations as factories dedicated to Ab secretion. Salient findings of this group and others, sometimes exhibiting differences, will be summarized with regard to the journey to a distinctive metabolic program in PCs.
Investigating the Addition of Ianalumab (VAY736) to Ibrutinib in Patients with Chronic Lymphocytic Leukemia (CLL) on Ibrutinib Therapy: Results from a Phase Ib Study
Authors: Kerry A. Rogers, Ian W. Flinn, Deborah M. Stephens, Thomas J. Kipps, Sarah Larson, Carolyn McGarry, Nadia B. Hassounah, Liangke Connie Gou, Janghee Woo, John C. Byrd
Journal: Blood (2021)
Cyclophosphamide, Etoposide, and Intermediate-Dose of Carboplatin; An Efficient Preparative Regimen for Autologous Transplantation for Patients with Lymphoma, a Good Alternative to Those Based on Carmustine. Experience with 108 Patients
Authors: Giovanni Ruiz, Amado J Karduss, Angela Maria Trujillo, Rosendo Perez, Angelica Cardona, Lina Callejas
Journal: Blood (2021)
Treatment with DC/AML Fusion Vaccine and CD3xCD123 Bi-Specific T-Cell Engager (CD123-CODV-TCE) for Treatment of Acute Myeloid Leukemia
Authors: Dina Stroopinsky, Anita G. Koshy, Jessica J. Liegel, Myrna Nahas, Giulia Cheloni, Joshua Hauser, Daniela Torres, Poorva Bindal, Maryam Rahimian, Lina Bisharat, Paula Fraenkel, Ozlem Yildirim, Helene Bonnevaux, Stephane Guerif, Donald Kufe, Jacalyn Rosenblatt, David Avigan
Journal: Blood (2021)
Single-Cell Multi-Omics Reveals That Pegylated Interferon-Alfa Treatment Differentially Redirects Mutated and Wildtype Hematopoietic Cell Differentiation Trajectories in <i>CALR-</i>mutated Essential Thrombocythemia (ET) Patients
Authors: Shira Rosenberg, Andrea Kubas-Meyer, Neelang Parghi, Nathaniel D. Omans, Neville Dusaj, Paulina Chamely, Eleni Mimitou, Amylou C. Dueck, Heidi E. Kosiorek, Rona Singer Weinberg, Peter Smibert, Ronan Chaligne, Dan A. Landau, Ronald Hoffman, Anna S Nam
Journal: Blood (2021)
Interleukin-1/Toll-like Receptor Inhibition Can Restore the Disrupted Bone Marrow Microenvironment in Mouse Model of Myelodysplastic Syndromes
Authors: Hiroki Kawano, Yuko Kawano, Mark W. LaMere, Daniel K. Byun, Caitlin L. Gordnier, Elizabeth A. LaMere, Tzu-Chieh Ho, John M. Ashton, Benjamin J. Frisch, Jeevisha Bajaj, Jane L. Liesveld, Laura M. Calvi, Michael W. Becker
Journal: Blood (2021)
Subcutaneous Epcoritamab in Combination with R-CHOP in Patients with Previously Untreated High-Risk Diffuse Large B-Cell Lymphoma: Preliminary Results from a Phase 1/2 Trial
Authors: David Belada, Jacob Haaber Christensen, Kristina Drott, Sylvia Snauwaert, Joshua Brody, Mayur Narkhede, Fritz Offner, Brian Elliot, Tracy Liu, Mariana Cota Stirner, Aqeel Abbas, Lorenzo Falchi, Michael Roost Clausen
Journal: Blood (2021)
CTIM-08. SAFETY, EFFICACY, AND SURVIVAL RESULTS FROM A PHASE 1 STUDY OF THE ONCOLYTIC ADENOVIRUS DNX-2401 FOLLOWED BY STANDARD OF CARE RADIOTHERAPY FOR NEWLY DIAGNOSED DIFFUSE INTRINSIC PONTINE GLIOMA (DIPG)
Authors: Jaime Gállego Pérez-Larraya, Marc Garcia-Moure, Ana Patiño-García, Marisol González-Huarriz, Jasper Van der Lugt, Itziar Astigarraga, Miguel García-Ariza, Blanca López-Ibor, Chris Jones, Alan Mackay, Ricardo Diez-Valle, Juan Fueyo, Candelaria Gomez-Manzano, Jessica Dobbs, Brett Ewald, Marta Alonso, Sonia Tejada
Journal: Neuro-Oncology (2021)

Abstract BACKGROUND Diffuse intrinsic pontine glioma (DIPG) is the most lethal pediatric brain tumor. Median overall survival (OS) with standard of care radiation therapy (RT) is approximately 8-10 months and 2-year survival is &amp;lt; 10%. A Phase 1 single-center study was conducted to evaluate the oncolytic adenovirus, DNX-2401 (tasadenoturev), followed by RT for DIPG. METHODS Newly-diagnosed DIPG patients 1-18 years old received a tumor biopsy through the cerebellar peduncle followed by intratumoral injection of 1e10 – 5e10 vp DNX-2401 and conventional RT 1-3 weeks later. RESULTS Subjects were enrolled (n=12) from December 2017 to January 2020 and had a median age of 9 years (range 3-18) and Lansky/Karnofsky performance scores of 90-100 (n=4; 33%) or 70-80 (n=8; 67%). Genetic assessment was completed for 11 subjects (92%) and histone 3 K27M mutations were identified in 10 subjects, including H3F3A (n=8), HIST2H3C (n=1), and HIST1H3B (n=1); 1 subject was H3 wildtype (n=1). TP53 mutations were identified in 5 subjects (42%). DNX-2401 was administered followed by RT (n=11; 92%). No dose-limiting toxicities were observed and the treatment regimen was well-tolerated. The most commonly reported adverse events (≥ 5 subjects), regardless of study drug relationship, include asthenia, headache, vomiting, pyrexia, and neurological deterioration. Three serious adverse events were reported including grade 3 abdominal pain, grade 3 lymphopenia, and grade 3 clinical deterioration. Tumor reductions were reported for 9 subjects (75%), including 2 confirmed (17%) and 2 unconfirmed (17%) responses per RAPNO criteria. As of the data cutoff, median OS is 19.7 months and OS-24 is 32% with follow-up ongoing for 3 subjects (26.9, 25.6, 13.7 months). CONCLUSIONS DNX-2401 followed by RT can be safely administered to DIPG. Survival outcomes are encouraging, thus warranting further evaluation in a Phase 2 study.
Daratumumab, Bortezomib and Dexamethasone (DVd) at First Relapse for Patients with Relapsed/ Refractory Multiple Myeloma (RRMM): A UK Myeloma Research Alliance (UK-MRA) Real-World Multicentre Analysis
Authors: Annabel McMillan, Supratik Basu, Kamaraj Karunanithi, Elizabeth A. Parkins, Edward Yan Ming Lau, Gordon Cook, Christopher Parrish, Firas Al-Kaisi, Guy Pratt, Salim Shafeek, Stephen William Hart Jenkins, Shivir Moosai, Danish Memon, Ceri A Bygrave, Xenofon Papanikolaou, Tara Maisel, Sandra Hassan, Gurvin Chander, Bhuvan Kishore, Farheen Karim, Georgina Talbot, Farooq A Wandroo, Dunsi Bolarinwa, Kwee Yong, Rakesh Popat
Journal: Blood (2021)
Management of Obesity in Adults with CKD
Authors: Allon N. Friedman, Lee M. Kaplan, Carel W. le Roux, Philip R. Schauer
Journal: Journal of the American Society of Nephrology (2021)

Obesity is a leading public health problem that currently affects over 650 million individuals worldwide. Although interest in the adverse effects of obesity has grown exponentially in recent years, less attention has been given to studying its management in individuals with CKD. This relatively unexplored area should be considered a high priority because of the rapid growth and high prevalence of obesity in the CKD population, its broad impact on health and outcomes, and its modifiable nature. This article begins to lay the groundwork in this field by providing a comprehensive overview that critically evaluates the available evidence related to obesity and kidney disease, identifies important gaps in our knowledge base, and integrates recent insights in the pathophysiology of obesity to help provide a way forward in establishing guidelines as a basis for managing obesity in CKD. Finally, the article includes a kidney-centric algorithm for management of obesity that can be used in clinical practice.
A systems genetics approach reveals PbrNSC as a regulator of lignin and cellulose biosynthesis in stone cells of pear fruit
Authors: Runze Wang, Yongsong Xue, Jing Fan, Jia-Long Yao, Mengfan Qin, Tao Lin, Qun Lian, Mingyue Zhang, Xiaolong Li, Jiaming Li, Manyi Sun, Bobo Song, Jiaying Zhang, Kejiao Zhao, Xu Chen, Hongju Hu, Zhangjun Fei, Cheng Xue, Jun Wu
Journal: Genome biology (2021)

Stone cells in fruits of pear (Pyrus pyrifolia) negatively influence fruit quality because their lignified cell walls impart a coarse and granular texture to the fruit flesh.
Abstract 9374: The Attenuation of Blood Pressure Lability Assessed by Frequency Analysis of Very Short-Term Continuous Blood Pressure Recording Reflects the Hemodynamic Aggravation in Heart Failure Patients with Reduced Ejection Fraction
Authors: Yasunori Suematsu, Keita Saku, Midori Miyazaki, Yuiko Yano, Tadaaki Arimura, Kanta Fujimi, Shin-ichiro Miura
Journal: Circulation (2021)

Introduction: The lower blood pressure variability (BPV) assessed by 24-hour ambulatory bloop pressure (BP) monitoring predicts cardiac events in heart failure with reduced ejection fraction (HFrEF) patients. However, the trends of BPV assessed by short-term continuous BP recording in HFrEF patients remains unknown. Hypothesis: We recently reported a novel method of BPV analysis which is focused on the power spectral density (PSD) of 30-min continuous BP recording. In the PSD, we defined the integrated area of PSD from 0.01Hz to 0.1Hz as an index of short-term BPV (BP lability index: BLI) (Figure 1). Since the worsening of cardiac function decreases the dynamic variability of BP, we hypothesized that reduced cardiac function lowers BLI. In this study, we investigated how the worsening of cardiac function alters BLI. Methods: We compared 33 HFrEF patients with 15 hypertensive (HT) patients as a normal cardiac function. We assessed baseline characteristics, the value of brain natriuretic peptide (BNP), echocardiography and 30-min continuous BP in those patients. BP time series in each subject was converted to PSD by the Fourier transform. Results: Compared to HT, HFrEF patients showed lower left ventricular ejection fraction (LVEF) (33.8±11.8 vs. 68.9±6.8 %, p&lt;0.001) and higher E/e’ (17.5±10.8 vs. 10.5±2.7, p=0.002), indicating the hemodynamic aggravation. In continuous BP, HFrEF reduced both averaged systolic BP (122.0±18.1 vs. 137.9±19.7 mmHg, p=0.006) and pulse pressure (50.1±13.9 vs. 59.2±14.9 mmHg, p=0.037). BLI was significantly lower in HFrEF patients than that in HT (2.07±0.98 vs. 2.64±0.95, p=0.010]. Interestingly, the patients with reduced LVEF and high E/e’ showed lower BLI (Figure 2). Furthermore, BLI negatively associated with BNP (r=-0.38, p=0.012) (Figure 3). Conclusions: BLI was lower in HFrEF patients than that in HT patients with normal cardiac function. BLI has a potential to develop a novel marker of hemodynamic assessment in HFrEF patients.
Peripheral Blood Complete Remission Provides Added Value to the Classical Definition of Morphologic Complete Remission - a Prospective Cohort Study of 1441 Patients with MDS, CMML and AML Treated within the Austrian Azacitidine Registry
Authors: Lisa Pleyer, Michael Pfeilstocker, Reinhard Stauder, Sonja Heibl, Heinz Sill, Michael Girschikofsky, Margarete Stampfl-Mattesberger, Christoph Tinchon, Bernd Hartmann, Andreas Petzer, Branka Petricevic, Clemens A. Schmitt, Sonja Vallet, Klaus Geissler, Wolfgang R. Sperr, Michael Leisch, Alexander Egle, Thomas Melchardt, Gudrun Piringer, Armin Zebisch, Sigrid Machherndl-Spandl, Dominik Wolf, Felix Keil, Hubert Angermann, Manuel Drost, Julian Larcher-Senn, Richard Greil
Journal: Blood (2021)
N6-methyladenosine reader IMP2 stabilizes the ZFAS1/OLA1 axis and activates the Warburg effect: implication in colorectal cancer
Authors: Senxu Lu, Li Han, Xiaoyun Hu, Tong Sun, Dongping Xu, Yalun Li, Qiuchen Chen, Weifan Yao, Miao He, Zhenning Wang, Huizhe Wu, Minjie Wei
Journal: Journal of Hematology & Oncology (2021)

Abstract Background Accumulating evidence shows that N6-methyladenine (m 6 A) modulators contribute to the etiology and progression of colorectal cancer (CRC). However, the exact mechanisms of m 6 A reader involved in glycolytic metabolism remain vague. This article aimed to crosstalk the m 6 A reader with glycolytic metabolism and reveal a new mechanism for the progression of CRC. Methods The relationship between candidate lncRNA and m 6 A reader was analyzed by bioinformatics, ISH and IHC assays. In vivo and in vitro studies (including MTT, CFA, trans-well, apoptosis, western blot, qRT-PCR and xenograft mouse models) were utilized to explore the biological functions of these indicators. Lactate detection, ATP activity detection and ECAR assays were used to verify the biological function of the downstream target. The bioinformatics, RNA stability, RIP experiments and RNA pull-down assays were used to explore the potential molecular mechanisms. Results We identified that the crosstalk of the m 6 A reader IMP2 with long-noncoding RNA (lncRNA) ZFAS1 in an m 6 A modulation-dependent manner, subsequently augmented the recruitment of Obg-like ATPase 1 (OLA1) and adenosine triphosphate (ATP) hydrolysis and glycolysis during CRC proliferation and progression. Specifically, IMP2 and ZFAS1 are significantly overexpressed with elevated m 6 A levels in CRC cells and paired CRC cohorts ( n = 144). These indicators could be independent biomarkers for CRC prognostic prediction. Notably, IMP2 regulated ZFAS1 expression and enhanced CRC cell proliferation, colony formation, and apoptosis inhibition; thus, it was oncogenic. Mechanistically, ZFAS1 is modified at adenosine +843 within the RGGAC/RRACH element in an m 6 A-dependent manner. Thus, direct interaction between the KH3–4 domain of IMP2 and ZFAS1 where IMP2 serves as a reader for m 6 A-modified ZFAS1 and promotes the RNA stability of ZFAS1 is critical for CRC development. More importantly, stabilized ZFAS1 recognizes the OBG-type functional domain of OLA1, which facilitated the exposure of ATP-binding sites (NVGKST, 32–37), enhanced its protein activity, and ultimately accelerated ATP hydrolysis and the Warburg effect. Conclusions Our findings reveal a new cancer-promoting mechanism, that is, the critical modulation network underlying m 6 A readers stabilizes lncRNAs, and they jointly promote mitochondrial energy metabolism in the pathogenesis of CRC.
Abstract 10212: Exposure to Volatile Organic Compounds - Acrolein, Crotonaldehyde, and Styrene - is Associated with Blood Pressure in the Jackson Heart Study
Authors: Katlyn E McGraw, Stacey L Konkle, Daniel W Riggs, Shesh N Rai, Natasha K DeJarnett, Zhengzhi Xie, Adebamike A Oshunbade, Rachel J Keith, Michael E Hall, Aruni Bhatnagar
Journal: Circulation (2021)

Introduction: Cardiovascular disease (CVD) is the leading cause of death from environmental exposures. Although exposure to particulate matter ≤2.5μm (PM 2.5 ) is an established risk factor for CVD, the contribution of other hazardous pollutant exposure to CVD risk is less clear. Hypothesis: We assessed the hypothesis that volatile organic compounds (VOCs) are associated with blood pressure in 778 nonsmokers from the Jackson Heart Study (JHS), a large, community based observational study of CVD in African Americans from the tri-county Jackson, MS area. Methods: We measured urinary metabolites of 17 parent VOCs in spot urine samples collected at baseline using UPLC/MS. We tested the association between VOC metabolites and blood pressure in nonsmokers using generalized linear models adjusted for age, sex, body mass index (BMI), estimated glomerular filtration rate, cholesterol to high-density lipoprotein ratio, triglycerides, blood pressure medications, diabetes, and PM 2.5 . Two measurements of systolic and diastolic blood pressure (SBP, DBP) in the resting state were averaged using a Hawksley random zero sphygmomanometer. Results: Included participants had a BMI of 31.3 ± 7.1 kg/m 2 (mean ± SD), had triglycerides of 99.9 ± 57.9 mg/dL, and a less than 10% prevalence of CVD events. More than one-third were affluent (37.8%) and almost half used blood pressure medications (46%). We found that metabolites of acrolein (CEMA) and crotonaldehyde (HPMMA) were associated with a 1.5mmHg (CI: 0.5, 2.7; p=0.01), and a 1.1mmHg higher (CI: 0.1, 2.0; p=0.02) SBP per interquartile range (IQR) of VOC metabolite, respectively. Additionally, we found a 0.5mmHg higher (CI: 0.1, 0.8; p= 0.01) DBP per IQR of styrene metabolite, MA. In subgroup analysis, the association between CEMA and MA and blood pressure persisted only in men. Conclusions: In conclusion, these findings suggest that exposure to VOCs (acrolein, crotonaldehyde, and styrene) may be a significant contributor to risk of hypertension among African American nonsmokers.
Abstract 9436: Impact of Pulmonary Artery Catheter Use in Cardiogenic Shock: A Systematic Review
Authors: Harsh Doshi, Mahek Shah, Alec Vishnevsky, Jalaj Garg, Rene Alvarez
Journal: Circulation (2021)

Introduction: Randomized controlled trials and systematic reviews evaluating the use of pulmonary artery catheters in the critically ill population have not shown beneficial effects on survival. However, many of those studies have excluded patients in cardiogenic shock. We address this evidence gap by providing a comprehensive meta-analysis to investigate the association between pulmonary artery catheter use and outcomes in patients with cardiogenic shock Hypothesis: Pulmonary artery catheter use in patients with cardiogenic shock is associated with improved mortality. Methods: We performed an extensive literature search using PubMed, MEDLINE, SCOPUS, and the Cochrane databases from January 1990 through June 2021. Data for final analysis was pooled using a random effects model. Odds ratios were used for effect size. Information on eligibility criteria, outcomes, and methodological quality was extracted by two independent reviewers. Primary study outcome was in-hospital mortality rate. Results: 16 studies were included in the analysis comprising 2,400,618 patients. Of those, 212,122 were managed with a pulmonary artery catheter (8.8%) and 2,188,496 were managed without one (91.2%). In patients with cardiogenic shock, pulmonary artery catheter use was associated with a statistically significant decrease in mortality (OR 0.82 [95% CI 0.73-0.92; p = 0.001]. The pulmonary artery catheter cohort was more likely to receive mechanical circulatory support (OR 2.16 [95% CI 1.90-2.45; p&lt;0.001]), left ventricular assist device (OR 3.09 [95% CI 1.96-4.86; p&lt;0.001]), and renal replacement therapy (OR 1.44 [95% CI 1.17-1.77; p=0.001]). Interestingly, when studies looking only at patients who developed cardiogenic shock due to acute myocardial infarction were analyzed, there was no statistically significant improvement in mortality (OR 0.945 [95% CI 0.75-1.20; p=0.64]). Conclusions: Pulmonary artery catheter use in patients with cardiogenic shock is associated with lower in-hospital mortality. Future studies differentiating pulmonary artery catheter use among various cardiogenic shock stages and phenotypes are needed.
Outcomes of Maintenance Treatment Post Autologous Stem Cell Transplantation in Newly Diagnosed Multiple Myeloma Patients: A Canadian Single Center Experience
Authors: Mina Dehghani, Shona Philip, Anthony Quint, Lenicio Siqueira, Selay Lam, Chai Wye Phua, Anargyros Xenocostas, Uday Deotare, Martha L Louzada
Journal: Blood (2021)
ML-0207/ASP8731: A Novel BACH1 Inhibitor That Induces Fetal Hemoglobin in Treatment of Sickle Cell Disease
Authors: Selva Nataraja, Maneet Singh, Shilpa Demes, Lyndsay Olson, Jeff Stanwix, Margaret Biddle, Emer Clarke, Yongzhao Huang, Julia Nguyen, Chunsheng Chen, Ping Zhang, Fuad Abdulla, Gregory M. Vercellotti, John D Belcher
Journal: Blood (2021)
A Phase 1 Dose-Escalation Study of the Oral CDK Inhibitor Voruciclib in Patients with Relapsed/Refractory B-Cell Malignancies or Acute Myeloid Leukemia (AML): Preliminary Results of the Completed Dose Escalation Stage in AML
Authors: Marina Konopleva, Danielle M. Brander, Krish Patel, Catherine S. Diefenbach, Yesid Alvarado, Olga Frankfurt, Monzr M. Al Malki, Alexey V. Danilov, Sameem Abedin, Kebede H. Begna, Avyakta Kallam, Richard G. Ghalie, Matthew S. Davids
Journal: Blood (2021)