tbuckley/cabot-search huggingface dataset:
STAT3 positively regulates IL-6 expression in lung cancer cells
Authors: Wei-Lun Huang, Hsuan-Heng Yeh, Wu-Chou Su
Journal: Cancer Research (2008)

886  IL-6 is a pleiotropic cytokine produced by many different cell types. It plays multiple roles largely depending on down-stream Jak/STAT3 pathway. Spontaneous production of IL-6 has been observed in various tumors. Furthermore, constitutive activation of STAT3 has also been shown in most of them. Upregulation of IL-6 has been associated with cancer pathogenesis, tumor progression, antiapoptosis, drug resistance, and poor clinical outcomes. Most of the studies emphasized the importance of NF-κB and AP-1 on IL-6 regulation. Others pointed out the potential roles of HIF-1α and p53. Though STAT3 decoy has been shown to non-specifically interrupted the expression of a series of cytokines including IL-6, the role of STAT3 in mediating IL-6 autocrine in cancer cells has not been clearly demonstrated. To answer this question we used lung adenocarcinoma cell line-PC14PE6/AS2 (AS2), in which STAT3 is constitutively active. We showed a time-dependent IL-6 autocrine in the AS2 cell. The Erk inhibitor (U0126) decreased about 80% of IL-6 secretion from AS2 cell but the NF-κB inhibitor (BAY11-7082) had no evident effect. Because blocking the activity of Jak/STAT3 signal by AG490 diminished IL-6 secretion by more than 60%, we speculated that Jak/STAT3 pathway may regulate IL-6 expression. To reveal the role of STAT3 in IL-6 secretion, we established several AS2-derived cell lines. AS2-S3C (S3C) cell was transfected with plasmids containing constitutively activated form of STAT3, AS2-S3D (S3D) cell was transfected with plasmids containing dominant-negative STAT3 with mutation at DNA binding domain, and AS2-S3F (S3F) cell was transfected with plasmids containing dominant-negative STAT3 with mutation at tyrosine phosphorylation site. The S3C cell expressed higher IL-6 mRNA and a 10-fold higher IL-6 secretion than did the control cells. The S3D and S3F cells showed a 50% decrease of IL-6 secretion than did the control cells. These results strongly suggested the role of STAT3 in regulating IL-6 expression. To confirm this, we introduced siRNA against STAT3 into AS2 cell. Knocking down STAT3 expression by siRNA decreased IL-6 secretion in AS2 cells. There was no inhibition on AS2 proliferation observed in the siRNA knock-down study. In summary, we have demonstrated the positive-feedback control of IL-6/STAT3 axis other than the well-known NF-κB and AP-1 pathway in a lung adenocarcinoma model.
Successful Treatment with Intrathecal Tocilizumab(IL-6 antibody) for 2 Cases of Graft-Versus Host Disease of the Central Nervous System after a Second Allogeneic HSCT from Haploidentical Donor
Authors: Ruirui Gui, Juanjuan Zhao, Yingling Zu, Lu Han, Yanli Zhang, Fengkuan Yu, Zhen Li, Huifang Zhao, Baijun Fang, Quande Lin, Quanli Gao, Yongping Song, Jian Zhou, Delong Liu
Journal: Blood (2018)
Abstract 257: Cortical Bone Stem Cell-Derived Exosomes Alter Wound Healing Response in Cardiac Fibroblasts and Cardiac Endothelial Cells
Authors: Giana Schena, Hajime Kubo, Yijun Yang, Eric Feldsott, Giulia Borghetti, Deborah Eaton, Jaslyn Johnson, Remus Berretta, Sadia Mohsin, Steven Houser
Journal: Circulation Research (2019)

Rationale: Post-myocardial infarction (MI) results in remodeling that leads to the development of heart failure. We have previously seen improvements in post-MI wound healing and scar formation as a result of administration of cortical bone stem cell derived exosomes (CBSC exosomes). Objectives: We sought to further elucidate the mechanism through which CBSC exosomes improved scar formation and altered wound healing through in vitro experimentation. We continued to explore the unique characteristics of CBSC exosomes in order to understand why they have anti-fibrotic effects. Methods and Results: We performed migration assays on cardiac endothelial cells and cardiac fibroblasts, and saw alterations in cell migration in both cell types upon treatment with mCBSC CM and mCBSC exosomes. We discovered that migration of CECs was reduced by 20% under the influence of mCBSC CM and mCBSC exosomes, but rescued when exosomes were removed from mCBSC CM. We discovered that the removal of exosomes from mCBSC CM slowed cardiac fibroblast migration by 40%. We saw a decrease in the quantity of pro-fibrotic mRNA in cardiac endothelial cells and cardiac fibroblasts after treatment with mCBSC exosomes. Adult cardiac endothelial cell mRNA levels of VEGFA, Col4A1, and VCAM were reduced nearly two fold from control untreated cell levels following mCBSC exosome treatment. Adult cardiac fibroblast Col1A1, Col3A1, Col4A1, and MMP2 mRNA levels were reduced one-fold from control untreated cell levels following mCBSC exosome treatment. Conclusions: Our findings show that the wound healing induced by CBSC treatment post-MI involves a mechanism altering the migration of endothelial cells, sustaining the migratory capabilities of fibroblasts, and decreasing the production of pro-fibrotic mRNA in cardiac fibroblasts and cardiac endothelial cells.
Poor Platelet Function on Sonoclot Signature Is Associated with High Incidence of Bleeding in Severe Immune Thrombocytopenia
Authors: Kundan Mishra, Aditya Jandial, Rajeev Sandal, Pradakshna Porchezhian, Samson Charan, Lad Deepesh Pravin Kumar, Gaurav Prakash, Alka Khadwal, R K Dhiman, Neelam Varma, Pankaj Malhotra
Journal: Blood (2018)
Interim PET Scan Does Not Predict Outcome in Primary Mediastinal B Cell Lymphoma Treated with R DA EPOCH
Authors: Mahesh Prahladan, Nicholas F Grigoropoulos, Sreetharan Munisamy, Andrew Hodson, Ashley Shaw, Penny Wright, Michael Wlliam, Ramesh Bulusu, Anna Sureda, Charles Crawley, Hk Cheow, George Follows
Journal: Blood (2012)
Androgen Derivatives Improve Blood Counts and Elongate Telomere Length in Patients with Dyskeratosis Congenita
Authors: Martin Kirschner, Monica Sofia Ventura Ferreira, Anne-Sophie Bouillon, Marcin W. Wlodarski, Michaela Schwarz, Stefan Balabanov, Stefan Wilop, Steffen Koschmieder, Jens P. Panse, Tim H. Brümmendorf, Fabian Beier
Journal: Blood (2018)
AB0096 Two cases of behcet’s disease with ulcers on glans penis
Authors: T Pirildar, T Turk, E Tunc, V Inal, G Keser, A Varol, E Doganavsargil, G Gumusdis
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> Behcet's Disease (BD), when first described in 1937, was consisted of three symptoms; recurrent oral, genital ulcerations and iridocyclitis. Today, it is known that BD is a multisystemic chronic vasculitic disorder which may involve both arteries and veins of all sizes. Although painful scrotal ulcers healing with scar formation are among the main clinical findings of BD, ulceration of glans penis is unusual. <h3>Objectives</h3> <h3>Methods</h3> <h3>Results</h3> We present two cases of BD with ulcers on glans penis. The first case is a 46-year-old man who presented with ulceration involving glans penis and diagnosed as BD after investigations. The second case was a 23-year-old man with established BD who later developed ulcers on glans penis during the course of the disease. In our 113 patients with BD, 102 patients (90.2%) had genital ulcers. Among these 102 patients having genital ulcers, only these two cases (1.9%) had ulcers localised on the glans penis. <h3>Conclusion</h3> In conclusion, the possibility of BD should also be considered in patients presenting with genital ulcer (s) with atypical localizations, such as glans penis, particularly in countries with a high prevalance of this disease.
Azacitidine With Or Without Entinostat For The Treatment Of Therapy-Related Myeloid Neoplasm: Further Results Of The E1905 North American Leukemia Intergroup Study
Authors: Thomas Prebet, Zhuoxin Sun, Rhett Ketterling, Peter L. Greenberg, Amer M. Zeidan, Mark R. Litzow, Janice L. Gabrilove, Harry Paul Erba, Elisabeth Paietta, Magdalena Czader, Steven D Gore, Martin S Tallman
Journal: Blood (2013)
Abstract 201: Roles of PIKfyve in Cardiac Fibroblast Migration
Authors: Guangming Luo, Lois S Weisman
Journal: Circulation Research (2019)

Cell migration is fundamental to proper development of the heart as well as other organs. Our characterization of a hypomorphic PIKfyve β-geo/β-geo mouse mutant, revealed that has an abnormally small heart, and raised the possibility that this could be due in part to a defect in cell migration. Moreover, a few studies suggested that PIKfyve, the sole lipid kinase that generates phosphatidylinositol 3,5-bisphosphate (PI3,5P2) and provides most of the PI5P, may have a role in migration of cultured cells. However, the localization of PIKfyve and the molecular mechanisms whereby PIKfyve regulates cell movement remain elusive. Here I show that inhibition of PIKfyve significantly impairs cell migration in cultured cell lines, as well as in primary cardiac fibroblasts, which are essential for proper heart development. Moreover, expression of a hyperactive PIKfyve mutant promotes cell migration. In order to detect the localization of endogenous PIKfyve, we used CRISPR-Cas9 genome editing to tag endogenous PIKfyve with an HA peptide at its N-terminus. Interestingly, in addition to PIKfyve localization on endosomes, a pool of PIKfyve was located at the cell leading edge. We observed PIKfyve in both lamellipodia and filopodia. Notably, we found that acute addition of PI3,5P2 or PI5P for 5 min altered filopodia dynamics. Our preliminary results suggest that PI3,5P2 and PI5P alter different properties of filopodia. These findings suggest that cell migration may be controlled in part by PI3,5P2 and PI5P which arise due to PIKfyve localization to the cell leading edge. Together, these studies suggest that mechanistic insights into how PIKfyve regulates cell migration may reveal new tools or concepts that can be utilized to study heart development in mammals.
EPID-23. PURSUIT OF AN INTERNATIONAL LANGUAGE OF GLIOMA RESEARCH: COMMON DATA ELEMENTS FOR THE LONGITUDINAL STUDY OF ADULT MALIGNANT GLIOMA
Authors: Laila Poisson, M C M Kouwenhoven, James Snyder, Kristin Alfaro-Munoz, Manpreet Kaur, Amanda Bates, Roel Verhaak, Colin Watts, Gelareh Zadeh, D Ryan Ormond, Elizabeth Claus, Mustafa Khasraw
Journal: Neuro-Oncology (2019)

Abstract As an uncommon cancer, clinical and translational studies of glioma rely on multi-center collaborations, confirmatory studies, and meta-analyses. Unfortunately, interpretation of results across studies is hampered by the absence of uniformly coded clinical data. Common Data Elements (CDE) represent a set of clinical features for which the language has been standardized for consistent data capture across studies, institutions and registries. We constructed CDE for the longitudinal study of adult malignant glioma. To identify the minimum set of CDE needed to describe the clinical course of glioma, we surveyed clinical standards, ongoing trials, published studies, and data repositories for frequently used data elements. We harmonized the identified clinical variables, filled in gaps, and structured them in a modular schema, defining CDE for patient demographics, medical history, diagnosis, surgery, chemotherapy, radiotherapy, other treatments, and outcomes. Multidisciplinary experts from the Glioma Longitudinal AnalySiS (GLASS) consortium, representing clinical, molecular, and data research perspectives, were consulted regarding CDE. The validity and capture feasibility of the CDE were assessed through harmonization across published studies, then validated with single institution retrospective chart abstraction. The refined CDE library is implemented in the Research Electronic Data Capture (REDCap) System, a secure web application for building and managing online surveys and databases. The work was motivated by the GLASS consortium, which supports the aggregation and analysis of complex genetic datasets used to define molecular trajectories for glioma. The goal is that modular REDCap implementation of CDE allows broad adoption in glioma research. To accommodate novel aspects, the CDE sets can be expanded through additional modules. In contrast, for efficient initiation of focused studies, subsets of CDE can be selected. Broad adoption of CDE will improve the ability to compare results and share data between studies, thereby maximizing the value of existing data sources and small patient populations.
A Mechanism For Switch Of Integrin Signaling Direction and a New Anti-Thrombotic Strategy Through Selective Outside-In Signaling Inhibition
Authors: Bo Shen, Xiaojuan Zhao, Kelly A O'Brien, Aleksandra Stojanovic-Terpo, Michael Keegan Delaney, Kyungho Kim, Jaehyung Cho, Stephen C.-T Lam, Xiaoping Du
Journal: Blood (2013)
An Epigenetic Mitotic Score Tracks the Proliferative History and Capacity of CLL Samples at Diagnosis and Is Associated with Clinical Outcome
Authors: Martí Duran-Ferrer, Ferran Nadeu, Guillem Clot, Renée Beekman, Tycho Baumann, Armando Lopez-Guillermo, Julio Delgado, Xose Puente, Carlos Lopez-Otin, Elias Campo, Inaki Martin Subero
Journal: Blood (2018)
Abstract 101: Identification of Novel MICU1 Interactors Independent of the mtCU Complex
Authors: Dhanendra Tomar, Joanne F Garbincius, Devin Kolmetzky, Manfred Thomas, Pooja Jadiya, John W Elrod
Journal: Circulation Research (2019)

MICU1 is an EF-hand containing mitochondrial protein that gates the mitochondrial Ca 2+ uniporter complex (mtCU) and directly interacts with the pore-forming subunit MCU. Previous studies have shown perinatal lethality and altered mitochondrial architecture in MICU1 knockout ( Micu1 -/- ) mice, phenotypes that are distinct from other knockout models of mtCU components, such as MCU, and thus are likely not explained solely by changes in matrix [Ca 2+ ] uptake. Further, our proteomic studies suggest that MICU1 exists in mitochondrial complexes void of MCU. This suggests that MICU1 may have cellular functions independent of mtCU regulation. To discern novel MICU1 molecular interactors we employed a biotinylation-based proteomic approach in Mcu -/- and Micu1 -/- cells to detect proteins interacting with MICU1 using fusion protein containing BioID2, a small biotin ligase for proximity-dependent labeling. Expression of MICU1-BioID2 in Mcu -/- cells allowed the identification of mtCU-independent interactors. Fast protein liquid chromatography (FPLC), blue native-PAGE, co-immunoprecipitation, live-cell Ca 2+ imaging, confocal and super-resolution imaging methods were used to confirm novel roles for MICU1 in mitochondrial biology. LC-MS analysis of biotinylated proteins after avidin-based purification identified the Mitochondrial Contact Site and Cristae Organizing System (MICOS) components IMMT, CHCHD2, and CHCHD3 as interacting with MICU1 (MICU1-BioD2 expressed in Micu1 -/- cells to avoid aberrant expression). These same MICOS components were identified in MCU -/- cells, suggesting that MICU1 could be involved in the regulation of MICOS independent of the mtCU. Further, the deletion of CHCHD2 resulted in the loss of MICOS and cristae disorganization without any observable effect on m Ca 2+ uptake. RNA sequencing revealed correlative expression changes in MICU1 and MICOS components in response to heart failure progression during transverse aortic constriction and myocardial infarction. These results suggest MICU1 likely serves cellular functions independent of the mtCU and may serve as a key regulator of Ca 2+ -dependent signaling (EF-hands) in other cellular processes that are dysregulated during heart failure.
Lenalidomide as Salvage Therapy after Allogeneic Stem′Cell Transplantation in Multiple Myeloma
Authors: Friederike Lehmann, Jean El-Cheikh, Tatjana Zabelina, Francis Ayuk, Christine Wolschke, Djordje Atanackovic, Ulrike Bacher, Axel R. Zander, Didier Blaise, Mohamad Mohty, Nicolaus Kroeger
Journal: Blood (2008)
Abstract 655: Protein Arginine Methyltransferase 6 Controls Cardiac Hypertrophy by Differential Arginine and Lysine Methylation of Histone H3
Authors: Vineesh Raveendran, Kamar Al-Haffar, Muhammed Kunhi, K Behlai, Waleed Al-Habib, Atli Eyjolsson, Jehad Al-Buraiki, Coralie I Poizat
Journal: Circulation Research (2019)

Heart failure remains a common cause of hospitalization and death worldwide. Heart failure can be caused by dysregulation of gene expression following abnormal expression of histone modifying enzymes. While lysine acetylation and methylation of histones have been the topic of many investigations, the role of arginine methylation in H3 has been overlooked. In an effort to understand regulatory mechanisms implicated in cardiac hypertrophy and heart failure, we assessed protein arginine methyl transferase (PRMT) members in the left ventricle of failing human hearts and control hearts. Our results show a specific up-regulation of PRMT6 mRNA in failing human hearts (5.95±2.16 fold in failing versus control, p=0.003) which also occurs in the compensatory phase of cardiac hypertrophy in mouse hearts subjected to pressure overload hypertrophy, and in neonatal rat ventricular myocytes (NRVM) stimulated with the hypertrophic agonist phenylephrine (PE). These changes are associated with a significant increase in arginine 2 asymmetric methylation of H3 (H3R2me2a) and reduced lysine 3 tri-methylation of H3 (H3K4me3) both in NRVM and in vivo . Importantly, forced expression of PRMT6 in NRVM stimulated with PE, enhances the expression of atrial natriuretic peptide (ANP). Conversely, silencing of PRMT6 reduces ANP protein expression and cell size, indicating that PRMT6 is critical for PE-mediated cardiac hypertrophy of NRVM. Also, silencing of PRMT6 reduces H3R2me2a, a mark associated with transcriptional repression. To evaluate the role of PRMT6 on cardiac contractility and global ion channel activity, we assessed contractility and global field potentials in live NRVM expressing normal and low level PRMT6 using the RTCA CardioECR system (ACEA Bioscience Inc.). Strikingly, reduced expression of PRMT6 drastically inhibits the contraction rate of NRVM, which is paralleled by a slight increase in the QT interval. All together, our results indicate that PRMT6 is a critical regulator of cardiac hypertrophy, implicating H3R2me2a as an important histone modification. Future studies investigating the specific gene programs regulated by PRMT6 are on their way. This study may help identify novel points of control to design new drugs for the treatment of heart failure.
Disparities in receipt of guideline concordant treatment for early-stage non-small cell lung cancer (NSCLC) patients in California.
Authors: Chelsea A Obrochta, James Don Murphy, Atsushi Nara, Caroline A. Thompson
Journal: Journal of Clinical Oncology (2019)

160 Background: Lung cancer is the second most commonly diagnosed cancer and the leading cause of cancer-related death in the U.S. In 2013, the U.S. Preventive Services Task Force began recommending lung cancer screening, which has resulted in earlier stage diagnosis for many tobacco users. The National Comprehensive Cancer Network (NCCN) provides evidence-based cancer treatment recommendations. Evidence suggests that a patient’s receipt of guideline-concordant treatment (GCT) increases survival, especially for screen-detected, earlier stage cancers. The objective of this study is to describe nonadherence to GCT and treatment delay in California NSCLC patients by sociodemographic characteristics and geography. Methods: 53,746 patients diagnosed with stage I/II NSCLC (2000-2015) in the California Cancer Registry were included in our study. We classified GCT according to NCCN guidelines and treatment delay as &gt;60 days after diagnosis. We report proportion of nonadherence to GCT and treatment delay overall, in 5-year periods and by patient race/ethnicity, socioeconomic status, payer, and marital status. Hotspot analysis is underway to identify regions at increased risk for nonadherence to GCT and treatment delay by patient residential census tract. Results: Overall, 55.9% of patients received GCT, 14.1% of patients received no treatment, and nonadherence to GCT increased over time. Among those who received treatment, 26.7% experienced a treatment delay. Nonadherence to GCT and delay was more frequent in patients who were black or Hispanic, unmarried, had public insurance, and were of lower socioeconomic status. Based on preliminary analyses, we expect nonadherence to GCT and treatment delay to be non-uniformly distributed across California neighborhoods. Conclusions: Nonadherence to GCT and treatment delay disproportionately affect priority populations. With rising numbers of early stage lung cancers due to screening smokers, administration of timely proper treatment of lung cancer is critical.
Minimal Residual Disease Risk-Stratification in Pediatric Mixed Phenotype Acute Leukemia: Results of a Multi-Center Cohort Study
Authors: Matthew J. Oberley, Sunil S. Raikar, Jemily Malvar, Gerald Wertheim, Alix E. Seif, Terri Guinipero, Richard Sposto, Karen R. Rabin, Jyotinder N. Punia, Reuven J. Schore, Dragos C. Luca, William G. Woods, Maurice R.G. O'Gorman, Etan Orgel
Journal: Blood (2018)
Comparing nonconscious nonverbal synchrony in racially concordant and racially discordant oncology interactions.
Authors: Lauren M. Hamel, Robert Moulder, Susan Eggly, Terrance Lynn Albrecht, Steven Boker, David W. Dougherty, Louis Penner
Journal: Journal of Clinical Oncology (2019)

169 Background: Communication in racially discordant (Black patient, non-Black physician) oncology interactions, which constitute about 80% of Black patients’ interactions, is generally poorer than in racially concordant interactions, and likely contributes to treatment disparities. However, the nonverbal behaviors that contribute to this problem are largely unknown. We examined nonverbal synchrony, or the nonconscious coordination of movement, which can reflect relationship quality. We hypothesized that racially discordant interactions will have lower levels of nonverbal synchrony. Methods: Data include video recordings of 68 Black patients and 163 White patients discussing treatment with their non-Black oncologists. Recordings were submitted to motion detection software to measure nonverbal synchrony. This software measures global synchrony (all correlated motion), peak synchrony (all positively correlated motion), who is leading the interaction (similar to who is leading in ballroom dancing), and how much synchrony occurs based on who is leading the interaction. Using multi-level models, we investigated whether nonverbal synchrony differed in racially concordant and racially discordant dyads. Results: Findings showed greater levels of global synchrony (p &lt; .05) and greater peak synchrony (p &lt; .05) in racially discordant interactions compared to racially concordant interactions. Global synchrony was the same in racially concordant interactions regardless of who was leading, but greater global synchrony occurred in racially discordant interactions when the patient was leading (p &lt; .05). Conclusions: This is the first study to use a dynamic jointly determined measure of behavior to assess oncology interactions. Contrary to our hypothesis, nonverbal synchrony was greater in racially discordant interactions than in racially concordant interactions. Patients are driving more of the synchrony in racially discordant interactions. This may suggest that patients in racially discordant interactions adapt to their physicians to bridge racial differences. Findings could contribute to physician training to enhance coordination and outcomes in oncology interactions.
Whole Genome Sequence Analysis of 22 MLL Rearranged Infant Acute Lymphoblastic Leukemias Reveals Remarkably Few Somatic Mutations: A Report From the St Jude Children‘s Research Hospital - Washington University Pediatric Cancer Genome Project
Authors: Anna K. Andersson, Jing Ma, Jianmin Wang, Xiang Chen, Michael Rusch, Gang Wu, John Easton, Matthew Parker, Susana C. Raimondi, Linda Holmfeldt, Amanda Larson Gedman, Guanchun Song, Jared Becksfort, Pankaj Gupta, Anatoly Ulyanov, Debbie Payne-Turner, Rosemary Sutton, Nicola V Venn, Albert Chetcuti, Amanda Rush, Daniel Catchpoole, Jesper Heldrup, Thoas Fioretos, Xin Hong, Charles Lu, Li Ding, Ching-Hon Pui, Sheila A Shurtleff, Tanja A Gruber, Charles G Mullighan, Elaine R Mardis, Richard K. Wilson, Jinghui Zhang, James R. Downing
Journal: Blood (2011)