tbuckley/cabot-search huggingface dataset:
Abstract 5196: CSFR-1R a potential therapeutic target in 4T1 xenograft breast cancer model
Authors: Jeanne Elia, Hong Zhang, Chiaokai Wen, Xifeng Yang
Journal: Cancer Research (2020)

Abstract The 4T1 cell line is a mouse mammary carcinoma which can mimic stage IV breast cancer in humans. When these cells are xenografted into a BALB/c mouse there is an infiltration of macrophages into the spleen, bone marrow and blood which was observed 11 days after engraftment. Increased cell proliferation was also detected in the spleen and blood. We found that 4T1 cells produced high levels of M-CSF in culture. In this study we attempt to neutralize the secreted cytokine from the tumor cells with anti-M-CSF (clone, A10603L) or to block the receptor with anti-M-CFR (CSF-1R) (clone, AFS98). Mice were xenografted with 4T1 cells then given one dose of 100 ug of neutralizing antibodies to either anti-M-CSF or anti-CSF-1R two days post tumor engraftment. Animals were sacrificed at multiple time points between 1-3 weeks. Treatment with one dose of anti-M-CSF showed minimal to no difference compared to the 4T1 xenograft group. Treatment with anti-CSF-1R showed reduced macrophage infiltration in the bone marrow, spleen and blood at day 11. BrdU incorporation levels dropped in the spleen and blood of these animals. Spleen size and total cell numbers were also reduced by 40% compared to the 4T1 xenograft group. Citation Format: Jeanne Elia, Hong Zhang, Chiaokai Wen, Xifeng Yang. CSFR-1R a potential therapeutic target in 4T1 xenograft breast cancer model [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 5196.
Incidence of Malformations After Early Pregnancy Exposure to Modafinil in Sweden and Norway
Authors: Carolyn E. Cesta, Anders Engeland, Pär Karlsson, Helle Kieler, Johan Reutfors, Kari Furu
Journal: JAMA (2020)

This pharmacoepidemiology study uses Scandinavian birth registry data to estimate the association between modafinil use during early pregnancy and major congenital malformations among infants born in Norway and Sweden between 2005-2006 and 2016-2017.
Comment on: ‘EULAR recommendations for the management of psoriatic arthritis with pharmacological therapies: 2019 update’ by Gossec<i>et al</i>
Authors: Chen-Yu Wei, Yung-Heng Lee, James Cheng Chung Wei
Journal: Annals of the Rheumatic Diseases (2020)

We read with great interest the published paper by Gossec et al 1 which provided updated European League Against Rheumatism (EULAR) recommendations for pharmacological therapies for psoriatic arthritis (PsA). In this full-scale, evidence-based guideline, the authors proclaimed 6 overarching principles and 12 recommendations for PsA. Recently, the field of pharmacotherapy for PsA has progressed rapidly and is replete with competing clinical trials working on the efficacy of plenty of drugs. However, in light of some evidence on therapeutic efficacy still being scarce today, there are a few points in this study that are worth mentioning.

First, for PsA with relevant skin involvement, the authors recommended methotrexate (MTX) as the standard treatment superior to other conventional synthetic disease-modifying antirheumatic drugs (csDMARDs). However, the evidence on the efficacy of MTX remains limited to date.2 Furthermore, the medication trends for psoriasis in Asia seemed to be …
Dysregulated Kras/YY1/ZNF322A/Shh transcriptional axis enhances neo-angiogenesis to promote lung cancer progression
Authors: Che-Chung Lin, I-Ying Kuo, Li-Ting Wu, Wen-Hui Kuan, Sheng-You Liao, Jayu Jen, You-En Yang, Cheng-Wei Tang, Yi-Rong Chen, Yi-Ching Wang
Journal: Theranostics (2020)

Angiogenesis enhances cancer metastasis and progression, however, the roles of transcription regulation in angiogenesis are not fully defined. ZNF322A is an oncogenic zinc-finger transcription factor. Here, we demonstrate a new mechanism of Kras mutation-driven ZNF322A transcriptional activation and elucidate the interplay between ZNF322A and its upstream transcriptional regulators and downstream transcriptional targets in promoting neo-angiogenesis. Methods: Luciferase activity, RT-qPCR and ChIP-qPCR assays were used to examine transcription regulation in cell models. In vitro and in vivo angiogenesis assays were conducted. Immunohistochemistry, Kaplan-Meier method and multivariate Cox regression assays were performed to examine the clinical correlation in tumor specimens from lung cancer patients. Results: We validated that Yin Yang 1 (YY1) upregulated ZNF322A expression through targeting its promoter in the context of Kras mutation. Reconstitution experiments by knocking down YY1 under KrasG13V activation decreased KrasG13V-promoted cancer cell migration, proliferation and ZNF322A promoter activity. Knockdown of YY1 or ZNF322A attenuated angiogenesis in vitro and in vivo. Notably, we validated that ZNF322A upregulated the expression of sonic hedgehog (Shh) gene which encodes a secreted factor that activates pro-angiogenic responses in endothelial cells. Clinically, ZNF322A protein expression positively correlated with Shh and CD31, an endothelial cell marker, in 133 lung cancer patient samples determined using immunohistochemistry analysis. Notably, patients with concordantly high expression of ZNF322A, Shh and CD31 correlated with poor prognosis. Conclusions: These findings highlight the mechanism by which dysregulation of Kras/YY1/ZNF322/Shh transcriptional axis enhances neo-angiogenesis and cancer progression in lung cancer. Therapeutic strategies that target Kras/YY1/ZNF322A/Shh signaling axis may provide new insight on targeted therapy for lung cancer patients.
FRI0213 Raynaud’s phenomenon in primary sjÖgren’s syndrome. prevalence and clinical characteristics in a series of 320 patients
Authors: M Garcia-Carrasco, M Ramos-Casals, J Rosas, A Siso, G De la Red, O Trejo, V Gil, R Cervera, J Font, M Ingelmo
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> <h3>Objectives</h3> To determine the prevalence of Raynaud’s phenomenon (RP) in a large series of patients with primary Sjögren’s syndrome (SS) and to identify the clinical and immunological features related to its presence. <h3>Methods</h3> In a cross-sectional study, we investigated 320 consecutive patients with primary SS (294 women and 26 men; mean age at onset 60 years; range 16–87 years). All patients fulfilled 4 or more of the diagnostic criteria for SS proposed by the European Community Study Group in 1993. Diagnosis of RP was done in SS patients with intermittent attacks of digital pallor and/or cyanosis, in the absence of any other associated disease or anatomical abnormalities. <h3>Results</h3> Raynaud’s phenomenon (RP) was present in 40 (13%) patients. All were women, with a mean age of 57 years (range, 18 to 78 years). RP precedes onset of sicca symptomatology in 18 (45%) patients. The main triggering factor was cold exposure, which induced RP in all patients, emotional stress in 12 and 2 patients had labour predisposition. Fifteen (38%) patients required pharmacological treatment with calcium channel blockers (12 patients) or angiotensin-converting enzyme inhibitors (2 patients) in the cold seasons. One patient required treatment with intravenous prostacyclin for ischaemic complications. When compared with SS patients without RP, those with RP showed a higher prevalence of articular involvement (50% vs 31%, p = 0.031), cutaneous vasculitis (30% vs 11%, p = 0.003), antinuclear antibodies (95% vs 65%, p &lt; 0.001), anti-Ro/SS-A (59% vs 31%, p &lt; 0.001) and anti-La/SS-B antibodies (44% vs 20%, p = 0.003). <h3>Conclusion</h3> We found RP in a 13% of patients with primary SS. Interestingly, RP was the first autoimmune symptomatology in almost 50% of these patients. These patients constituted a subset of SS with a higher frequency of some extraglandular features and positive immunological markers. In contrast, RP have a milder course in primary SS, with no vascular complications and needing pharmacological treatment in only 40% of patients. The clinical course of RP seems to be milder in patients with primary SS than in other systemic autoimmune diseases such as systemic sclerosis.
Impact of blood-brain barrier permeabilization induced by ultrasound associated to microbubbles on the brain delivery and kinetics of cetuximab: An immunoPET study using 89Zr-cetuximab
Authors: Vu Long Tran, Anthony Novell, Nicolas Tournier, Matthieu Gerstenmayer, Arnaud Schweitzer-Chaput, Claudia Mateos, Benoit Jego, Alizée Bouleau, Hervé Nozach, Alexandra Winkeler, Bertrand Kuhnast, Benoit Larrat, Charles Truillet
Journal: Journal of Controlled Release (2020)
Abstract 16238: Risk Factors for Early Neurological Injury in Infants Requiring Deep Hypothermic Circulatory Arrest and/or Selective Cerebral Perfusion
Authors: Katerina Boucek, Cathy Smith, Monica Olsen, Ricardo Argueta-Morales, William M DeCampli
Journal: Circulation (2013)

Introduction: Some studies associate deep hypothermic circulatory arrest (DHCA) and selective cerebral perfusion (SCP) with neurological injury. For DHCA the effect seems to be duration-dependent, ...
A Cell-Autonomous Signature of Dysregulated Protein Phosphorylation Underlies Muscle Insulin Resistance in Type 2 Diabetes
Authors: Thiago M. Batista, Ashok Kumar Jayavelu, Nicolai J. Wewer Albrechtsen, Salvatore Iovino, Jasmin Lebastchi, Hui Pan, Jonathan M. Dreyfuss, Anna Krook, Juleen R. Zierath, Matthias Mann, C. Ronald Kahn
Journal: Cell Metabolism (2020)
Immune pathogenesis of COVID-19–related multisystem inflammatory syndrome in children
Authors: Anne H. Rowley, Stanford T. Shulman, Moshe Arditi
Journal: Journal of Clinical Investigation (2020)

An emerging understanding of MIS-CWhen cases of severe acute respiratory syndrome coronavirus 2-associated (SARS-CoV-2-associated) multisystem inflammatory syndrome in children (MIS-C) were initially reported from Europe, the predominant clinical findings were persistent fever, marked abdominal symptoms, cytokine storm, myocardial dysfunction, and cardiogenic shock with left ventricular dysfunction in the setting of multisystem inflammation, reminiscent of toxic shock syndrome (TSS) or Kawasaki disease shock syndrome (KDSS) and requiring ICU care (1).Other clinical findings included those commonly observed in children with a variety of different infections and noninfectious illnesses, such as conjunctival injection, oral mucosal changes, and rash, features that are overlapping with TSS and incomplete Kawasaki disease.Because mucocutaneous findings are present in children with Kawasaki disease, and because patients with MIS-C sometimes developed mild coronary artery dilation, diagnostic confusion initially led some clinicians to conclude that the two conditions were the same (2).
Abstract 2738: Role of KLF8 for drug-resistant metastasis of breast cancer
Authors: Jie Hao, Heng Lu, Debarati Mukherjee, Aiqin Sun, Lin Yu, Jihe Zhao
Journal: Cancer Research (2020)

Abstract Metastasis and drug resistance are intertwined processes that are responsible for the vast majority of patient deaths from breast cancer. The underlying mechanisms still need to be investigated extensively. We previously demonstrated that KLF8 activates CXCR4 transcription in metastatic breast cancer. Here, we report a novel signaling mechanism that turns a localized metastasis into multiple organ metastases in response to chemotherapy. We show that KLF8 expression in breast cancer cells can be over-induced by chemotherapeutic drugs. Data from large-cohorts of patients indicates that post-chemotherapy there is a close correlation between the aberrant high levels of KLF8 and CXCR4, and this correlation is well associated with drug resistance, metastasis, and poor prognosis. To mimic this upregulation, we overexpressed KLF8 or CXCR4 in a human breast cancer cell line known to metastasize to the lungs only after i.v. injection in the nude mice. Surprisingly, we found that these KLF8 or CXCR4 overexpressing cells metastasized all over the body after orthotopically implanted. Tube formation assay, Ki67 staining, and western blotting revealed that KLF8 or CXCR4 overexpression promoted angiogenic vascular growth involving increased expression and secretion of VEGF protein. We also performed the matrigel-on-top 3-D culture to mimic the colonization step of metastasis and found that KLF8 or CXCR4 overexpression strongly enhances the formation of filopodium-like protrusions and proliferation via CXCR4 stimulation. Taken together, these results suggest that the chemo-induction of KLF8 upregulation is critical for drug resistance and systemic metastasis through enhanced tumor angiogenesis and colonization via CXCR4 over-activation. This discovery identifies the KLF8-CXCR4 signaling axis as a potentially new therapeutic target for breast cancer. Citation Format: Jie Hao, Heng Lu, Debarati Mukherjee, Aiqin Sun, Lin Yu, Jihe Zhao. Role of KLF8 for drug-resistant metastasis of breast cancer [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 2738.
Treatment-Specific Associations Between Brain Activation and Symptom Reduction in OCD Following CBT: A Randomized fMRI Trial
Authors: Luke J. Norman, Kristin A. Mannella, Huan Yang, Mike Angstadt, James L. Abelson, Joseph A. Himle, Kate D. Fitzgerald, Stephan F. Taylor
Journal: American Journal of Psychiatry (2020)

The authors sought to examine whether brain activity is associated with treatment response to cognitive-behavioral therapy (CBT) in adolescents and adults with obsessive-compulsive disorder (OCD), and whether any associations are treatment specific relative to an active control psychotherapy (stress management therapy; SMT).Eighty-seven patients with OCD (age range 12-45 years; 57 female, 39 medicated) were randomly assigned to receive 12 weeks of CBT or SMT. Prior to treatment, functional MRI scans were conducted in patients performing an incentive flanker task, which probes brain activation to both cognitive control and reward processing. Voxelwise linear mixed-effects models examined whether baseline brain activation was differentially associated with change in scores on the Yale-Brown Obsessive Compulsive Scale (standard or Children's version) over the course of CBT or SMT treatment.Within the CBT group, a better treatment response was significantly associated with greater pretreatment activation within the right temporal lobe and rostral anterior cingulate cortex during cognitive control and within the ventromedial prefrontal, orbitofrontal, lateral prefrontal, and amygdala regions during reward processing. In contrast, reduced pretreatment activation within a largely overlapping set of regions was significantly associated with a better treatment response to SMT.The study findings demonstrate that associations between brain activation and treatment response were treatment specific to CBT relative to a control psychotherapy and that these associations were stable from adolescence to mature adulthood. Such treatment-specific associations are important for the development of biomarkers to personalize treatment in OCD.
Immunological considerations for COVID-19 vaccine strategies
Authors: Mangalakumari Jeyanathan, Sam Afkhami, Fiona Smaill, Matthew S. Miller, Brian D. Lichty, Zhou Xing
Journal: Nature reviews. Immunology (2020)

The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the most formidable challenge to humanity in a century. It is widely believed that prepandemic normalcy will never return until a safe and effective vaccine strategy becomes available and a global vaccination programme is implemented successfully. Here, we discuss the immunological principles that need to be taken into consideration in the development of COVID-19 vaccine strategies. On the basis of these principles, we examine the current COVID-19 vaccine candidates, their strengths and potential shortfalls, and make inferences about their chances of success. Finally, we discuss the scientific and practical challenges that will be faced in the process of developing a successful vaccine and the ways in which COVID-19 vaccine strategies may evolve over the next few years. This Review outlines the guiding immunological principles for the design of coronavirus disease 2019 (COVID-19) vaccine strategies and analyses the current COVID-19 vaccine landscape and the challenges ahead.
An uninvited commentary on “Arthroscopic partial meniscectomy combined with medical exercise therapy versus isolated medical exercise therapy for degenerative meniscal tear: A meta-analysis of randomized controlled trials” (Int J Surg. 2020 Jul;79:222-232. doi: 10.1016/j.ijsu.2020.05.035)
Authors: Shushan Zhao, Yong Zhu, Zhe Ruan
Journal: International Journal of Surgery (2020)
Abstract 1824: Coordinate translational control of the kras signaling pathway
Authors: Kamini Singh, Jianan Lin, Nicolas Lecomte, Prathibha Mohan, Steve D. Leach, Zhengqing Ouyang, Hans-Guido Wendel
Journal: Cancer Research (2020)

Abstract G-quadruplex (GQ) elements are conserved translational control elements that induce a requirement for RNA helicase activity for efficient mRNA translation. Computational structure analyses identify multiple GQ elements in the 5'UTRs of mRNAs encoding KRAS and key downstream signalling molecules. KRAS is a key oncogene in pancreatic ductal adenocarcinoma (PDAC) and many other cancers and except for the specific G12C KRAS mutation we do not have pharmacological inhibitors. We find that KRAS and downstream signalling molecules including PI3K, RALA, RAC2, MYC, MET, and YAP1 strictly depend on the RNA helicase eIF4A for their translation. This implies a potential utility for eIF4A/DDX2 inhibitors. CR31B is a silvestrol analogue that efficiently and selectively blocks eIF4A. CR31B kills PDAC cells at nanomolar concentrations and has significant single agent in vivo efficacy across xenograft, primary PDX, and murine models of PDAC. Together, our findings reveal coordinate, GQ- and eIF4A-mediated control of the translation of key RAS signalling molecules as a vulnerability in KRAS-driven pancreatic cancer. Citation Format: Kamini Singh, Jianan Lin, Nicolas Lecomte, Prathibha Mohan, Steve D. Leach, Zhengqing Ouyang, Hans-Guido Wendel. Coordinate translational control of the kras signaling pathway [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 1824.
Osteopontin Expression Identifies a Subset of Recruited Macrophages Distinct from Kupffer Cells in the Fatty Liver
Authors: Anneleen Remmerie, Liesbet Martens, Tinne Thoné, Angela Castoldi, Ruth Seurinck, Benjamin Pavie, Joris Roels, Bavo Vanneste, Sofie De Prijck, Mathias Vanhockerhout, Mushida Binte Abdul Latib, Lindsey Devisscher, Anne Hoorens, Johnny Bonnardel, Niels Vandamme, Anna Kremer, Peter Borghgraef, Hans Van Vlierberghe, Saskia Lippens, Edward Pearce, Yvan Saeys, Charlotte L. Scott
Journal: Immunity (2020)

Metabolic-associated fatty liver disease (MAFLD) represents a spectrum of disease states ranging from simple steatosis to non-alcoholic steatohepatitis (NASH). Hepatic macrophages, specifically Kupffer cells (KCs), are suggested to play important roles in the pathogenesis of MAFLD through their activation, although the exact roles played by these cells remain unclear. Here, we demonstrated that KCs were reduced in MAFLD being replaced by macrophages originating from the bone marrow. Recruited macrophages existed in two subsets with distinct activation states, either closely resembling homeostatic KCs or lipid-associated macrophages (LAMs) from obese adipose tissue. Hepatic LAMs expressed Osteopontin, a biomarker for patients with NASH, linked with the development of fibrosis. Fitting with this, LAMs were found in regions of the liver with reduced numbers of KCs, characterized by increased Desmin expression. Together, our data highlight considerable heterogeneity within the macrophage pool and suggest a need for more specific macrophage targeting strategies in MAFLD.
Abstract LB-310: Whole-exome sequencing reveals genetic underpinnings of salivary adenoid cystic carcinoma and tongue carcinoma in Chinese population
Authors: Ning Li, Shuhang Wang, Yue Yu, Yuan Fang, Huiyao Huang, Dawei Wu, Hong Fang, Chao Sun, Anqi Yu, Qi Fan, Shi-Yuan Cheng
Journal: Cancer Research (2020)

Abstract Background: Salivary adenoid cystic carcinoma (ACC) and oral tongue squamous cell carcinoma (OTSCC) are rare malignancies with low incidence and dismal prognosis. The molecular underpinnings of these remain poorly understood, particularly in Asian population. Methods: Through a whole-exome sequencing analysis of 13 OTSCC and 30 ACC patients, a systematic overview of the mutational features in single-nucleotide variations, copy number variations and chromosomal variations were illustrated. Results: In addition to the well-characterized alterations previously reported in Caucasian patients, such as TP53 mutations (11/13, 84.6%) in OTSCC and MYB-NFIB fusion in ACC (11/30, 36.7%), we also observed several novel genetic changes, including FOXP1-TEX261 fusion (1/13, 7.7%) and MYB-FMO5 fusion (1/30, 3.3%) in OTSCC and ACC respectively, which might play a role in facilitating tumor progression. The data exhibited promising translational value as numerous actionable genes were identified with mutations. 76.9% OTSCC and 20% salivary ACC harbored at least one alteration in actionable genes, mutations in CDKN2A (4/13, 30.8%), NTRK3 (3/13, 23.1%) in OTSCC and FGFR2 (2/30, 6.7%), BRAF (2/30, 6.7%) in salivary gland ACC, suggesting targeted immunotherapy might be an effective intervention. Instead of MYB-independent NFIB fusions previously reported in ACC, only NFIB-independent MYB fusions were found in our cohort, indicating that alterations in NFIB rather than MYB might be essential to ACC tumorigenesis. Conclusions: This study reveals the genetic underpinnings of two rare malignancies in Chinese population, illustrating consistent mutational features with published literature as well as demonstrating several distinct genetic alterations, warranting further investigations. Citation Format: Ning Li, Shuhang Wang, Yue Yu, Yuan Fang, Huiyao Huang, Dawei Wu, Hong Fang, Chao Sun, Anqi Yu, Qi Fan, Shi-Yuan Cheng. Whole-exome sequencing reveals genetic underpinnings of salivary adenoid cystic carcinoma and tongue carcinoma in Chinese population [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr LB-310.