tbuckley/cabot-search huggingface dataset:
Abstract TMIM-081: THE HYPOXIC TUMOR-MESOTHELIAL NICHE PROMOTES OVARIAN CANCER METASTASIS THROUGH COLLAGEN REMODELING
Authors: Suchitra Natarajan, Katie Foreman, Michaela Soriano, Hussein Shehade, Daniel Fregoso, Joshua Eggold, Ninna S. Rosen, Sarah Heilshorn, Adam J. Krieg, Venkatesh Krishnan, Oliver Dorigo, Subarna Sinha, Katherine C. Fuh, Erinn B. Rankin
Journal: Clinical Cancer Research (2019)

Abstract High grade serous ovarian cancer (HGSOC) is a leading cause of cancer related deaths among women. The primary cause of morbidity and mortality in HGSOC patients is metastasis to organs within the peritoneal cavity. Mesothelial cells line the surface of peritoneal organs and are a key stromal cell in HGSOC metastatic niche. However, the mechanisms by which mesothelial cells promote ovarian cancer peritoneal metastasis remain largely unknown. Here we demonstrate that tumor associated mesothelial cells promote tumor invasion by increasing collagen deposition and remodeling. Mechanistically, we demonstrate the tumor-mesothelial niche is hypoxic where both tumor cells and mesothelial cells express the hypoxia inducible factors HIF-1 and HIF-2 and their downstream target gene lysyl oxidase (LOX). LOX is an enzyme that crosslinks collagen fibrils to promote collagen remodeling. In tumor-mesothelial co-culture experiments, we demonstrate that hypoxia enhances extracellular fibrillar collagen deposition by mesothelial cells. Conditioned media from hypoxic tumor-mesothelial co-cultures promotes collagen remodeling and HGSOC tumor cell invasion. Genetic inactivation of either HIF-1 and HIF-2 or LOX reduces the hypoxic induction of collagen remodeling and tumor cell invasion. Importantly, pharmacologic inhibition of HIF-1 and HIF-2 with digoxin reduces the colonization of disseminated HGSOC cells to the omentum, the preferential migration site of peritoneal cancer metastasis. Moreover, pharmacologic inhibition of LOX with BAPN (beta-aminopropionitrile) is sufficient to inhibit metastatic tumor burden and collagen remodeling at metastatic sites in preclinical models of HGSOC metastasis. These data reveal a novel role for mesothelial cells in the production of type I collagen and collagen remodeling in the HGSOC metastatic microenvironment. Furthermore, these studies demonstrate a role for the HIF/LOX signaling axis in the HGSOC tumor-mesothelial niche that can be therapeutically targeted to inhibit collagen remodeling and ovarian cancer metastatic progression. Citation Format: Suchitra Natarajan, Katie Foreman, Michaela Soriano, Hussein Shehade, Daniel Fregoso, Joshua Eggold, Ninna S. Rosen, Sarah Heilshorn, Adam J. Krieg, Venkatesh Krishnan, Oliver Dorigo, Subarna Sinha, Katherine C. Fuh, Erinn B. Rankin. THE HYPOXIC TUMOR-MESOTHELIAL NICHE PROMOTES OVARIAN CANCER METASTASIS THROUGH COLLAGEN REMODELING [abstract]. In: Proceedings of the 12th Biennial Ovarian Cancer Research Symposium; Sep 13-15, 2018; Seattle, WA. Philadelphia (PA): AACR; Clin Cancer Res 2019;25(22 Suppl):Abstract nr TMIM-081.
Increased ventilation heterogeneity in asthma can be attributed to proximal bronchioles
Authors: Brody Foy, David Kay, Salman Siddiqui, Chris Brightling, Manuel Paiva, Sylvia Verbanck
Journal: European Respiratory Journal (2019)

<b>By combining patient-specific CT-based airways with a clinically validated lung model, the proximal bronchioles were identified as the airways where structural abnormality can explain the increased convective ventilation heterogeneity in asthma patients</b> http://bit.ly/2COT0Qh
Differential Morbidity by Ethnicity in Long-Term Survivors of Hematopoietic Cell Transplantation (HCT): A Report from the Bone Marrow Transplant Survivor Study (BMTSS)
Authors: Saro Armenian, Can-Lan Sun, Liton Francisco, K. Scott Baker, Stephen J. Forman, Smita Bhatia
Journal: Blood (2008)
Influence of Fibronectin,(FN), Adhesion on Gene Expression Profiles, (GEP), of Isolated Patient Myeloma Cells.
Authors: Melissa Alsina, Ramadevi Nimmanapalli, Mackley A. Paul, Gerbino Elvira, Lori Hazlehurst, Steven Enkemann, Beam Craig, William S. Dalton
Journal: Blood (2004)
Standard Versus Dose-Intensified Chemotherapy with Granulocyte Colony-Stimulating Factor for Malignant Lymphoma: Evaluation of Risk for Acute Myeloid Leukemia or Myelodysplastic Syndrome
Authors: Gary H. Lyman, David C. Dale, Debra Wolff, Eva Culakova, Nicole M. Kuderer, Marek S. Poniewierski, Jeffrey Crawford
Journal: Blood (2008)
Stunned myocardium and oxygen free radicals. Sarcolemmal membrane damage due to oxygen free radicals.
Authors: Masanori Kaneko, Hideharu Hayashi, Akira Kobayashi, Noboru Yamazaki, Naranjan S Dhalla
Journal: Circulation (1991)

Reperfusion after reversible ischemia has been shown to result in prolonged depression of contractile function (myocardial stunning). Recent studies suggest that oxygen free radicals may mediate postischemic dysfunction. Since heart sarcolemmal membranes, which contain several types of enzymes. ion channels and receptors play important roles to maintain cell functions, the pre-sent study was undertaken to examine the effects of oxygen free radicals on heart sarcolemmal membrane functions in vitro. In the presence of a superoxide anion radical-generating system (2mM xanthine plus 0.03 U/ml xanthine oxidase), sarcolemmal Ca2+-stimulated ATPase activity and ATP-dependent Ca2+ accumulation were inhibited in an incubating time-dependent manner. Both lipid peroxidation (r=0.82) and sulthydryl group content (r=0.95) showed significant correlations with Ca2+-stimulated ATPase activity. ATP-indenpendent Ca2+ bindings were increased upon treating the membranes with xanthine plus xanthine oxidase. Voltage-dependent Ca2+-channels were also affected by oxygen free radicals. The maximal number of binding sites (Bmax) for [3H]-nitrendipine binding was depressed without any changes in dissociation constant (Kd). The effects of oxygen free radicals on adrenergic receptors were more complex. Bmax for [3H]-dihydroalprenolol (DHA) binding (β-receptor) was increased whereas Bmax for [3H]-prazosin binding (α1-receptor) was de-creased after incubating the membrane with xanthine plus xanthine oxidase. Kd for [3H]-DHA or [3H]-prazosin binding was increased. Superoxide dismutase showed protective effects on the changes in these membrane functions due to xanthine plus xanthine oxidase. It is suggested that oxygen free radicals damage heart sarcolemmal mambrane functions which may lead to cardiac dysfunction. in the stunned myocardium.
Testing bronchodilator responsiveness
Authors: Christer Janson, Andrei Malinovschi, Andre F.S. Amaral, Simone Accordini, Jean Bousquet, A. Sonia Buist, Judith Garcia-Aymerich, Louisa Gnatiuc, Wan Tan, Kjell Torén, Torsten Zuberbier, Peter Burney
Journal: European Respiratory Journal (2019)

<b>Neither flow-related nor volume-related bronchodilator reversibility were independently associated with the symptom burden, health status or dyspnoea in the COPD population</b>http://bit.ly/2rigD1r
Mesenchymal Stromal Cell Co-Culture Enhances Insulin-Like Growth Factor Binding Protein 2 - Augmented Ex Vivo Cultures of Human Cord Blood in a Viability Supporting, Contact-Dependent Process Involving the Rescue of Cells from Early Apoptosis
Authors: Pat PY Chu, Arun Prasath, Zhihong Li, Sudipto Bari, Justina ML Ang, Xiubo Fan, Chengcheng Zhang, Harvey F. Lodish, William YK Hwang
Journal: Blood (2008)
Repetitive DNA Hypomethylation in Multiple Myeloma
Authors: Sonia Fabris, Valentina Bollati, Laura Mosca, Valeria Pegoraro, Domenica Ronchetti, Gabriella Ciceri, Luca Baldini, Fortunato Morabito, Giorgio Lambertenghi Deliliers, Pier Alberto Bertazzi, Andrea Baccarelli, Antonino Neri
Journal: Blood (2008)
Plasma Cell Gene-Expression Profiles in Patients with Systemic AL Amyloidosis: Responses to Melphalan and Stem Cell Transplant Are Associated with Differential Expression of Genes Involved in Translation, Protein Degradation and Detoxification.
Authors: Raymond L. Comenzo, Ping Zhou, Limin Wang, Stephen D. Nimer, Adam B. Olshen
Journal: Blood (2005)
Preemptive Immunotherapy with Highly Purified CD56+/CD3− Natural Killer Cells after Haploidentical Stem Cell Transplantation. A Prospective Phase II Study in 2 Centers.
Authors: Jakob R. Passweg, Ulrike Koehl, Martin Stern, Torsten Tonn, Sandrine Meyer-Monard, Peter Bader, Johannes Rischewski, Jan Soerensen, Michael Paulussen, Alois Gratwohl, Thomas Klingebiel, Andre Tichelli, Dirk Schwabe
Journal: Blood (2006)
Vasomotion as a Driving Force for Paravascular Clearance in the Awake Mouse Brain
Authors: Susanne J. van Veluw, Steven S. Hou, Maria Calvo-Rodriguez, Michal Arbel-Ornath, Austin C. Snyder, Matthew P. Frosch, Steven M. Greenberg, Brian J. Bacskai
Journal: Neuron (2019)

Paravascular drainage of solutes, including β-amyloid (Aβ), appears to be an important process in brain health and diseases such as Alzheimer's disease (AD) and cerebral amyloid angiopathy (CAA). However, the major driving force for clearance remains largely unknown. Here we used in vivo two-photon microscopy in awake head-fixed mice to assess the role of spontaneous vasomotion in paravascular clearance. Vasomotion correlated with paravascular clearance of fluorescent dextran from the interstitial fluid. Increasing the amplitude of vasomotion by means of visually evoked vascular responses resulted in increased clearance rates in the visual cortex of awake mice. Evoked vascular reactivity was impaired in mice with CAA, which corresponded to slower clearance rates. Our findings suggest that low-frequency arteriolar oscillations drive drainage of solutes. Targeting naturally occurring vasomotion in patients with CAA or AD may be a promising early therapeutic option for prevention of Aβ accumulation in the brain.
Histone Deacetylase 3 (HDAC3), a Component of N-CoR-TBL1/R1 Chromatin Remodeling Co-Repressor Complex, Is Recruited to the Target Gene Promoters by PML-RARα To Repress the Transcription In Vivo.
Authors: Akihiro Tomita, Akihide Atsumi, Hitoshi Kiyoi, Tomoki Naoe
Journal: Blood (2005)
A Plateau after 30 Months of Follow-Up in B -Lineage Childhood Acute Lymphoblastic Leukemia (ALL) with t(1;19)(q23;p13)/E2A-PBX1?.
Authors: André Baruchel, Sylvie Chevret, Anne Auvrignon, Paola Ballerini, Gérard Michel, Jean Gabert, Christiane Vermylen, Yves Perel, Chrystèle Bilhou-Nabera, Odile Lejars, Claudine Schmitt, Pierre Jonveaux, Jean Soulier, Jacqueline Vandenaker, Marie-Françoise Auclerc, Thierry Leblanc, Guy Leverger
Journal: Blood (2005)
Gut microbiota modulate dendritic cell antigen presentation and radiotherapy-induced antitumor immune response
Authors: Mireia Uribe-Herranz, Stavros Rafail, Silvia Beghi, Luis Gil-de-Gómez, Ioannis Verginadis, Kyle Bittinger, Sergey Pustylnikov, Stefano Pierini, Renzo Perales-Linares, Ian A. Blair, Clementina A. Mesaros, Nathaniel W. Snyder, Frederic Bushman, Constantinos Koumenis, Andrea Facciabene
Journal: Journal of Clinical Investigation (2019)

Alterations in gut microbiota impact the pathophysiology of several diseases, including cancer. Radiotherapy (RT), an established curative and palliative cancer treatment, exerts potent immune modulatory effects, inducing tumor-associated antigen (TAA) cross-priming with antitumor CD8+ T cell elicitation and abscopal effects. We tested whether the gut microbiota modulates antitumor immune response following RT distal to the gut. Vancomycin, an antibiotic that acts mainly on gram-positive bacteria and is restricted to the gut, potentiated the RT-induced antitumor immune response and tumor growth inhibition. This synergy was dependent on TAA cross presentation to cytolytic CD8+ T cells and on IFN-γ. Notably, butyrate, a metabolite produced by the vancomycin-depleted gut bacteria, abrogated the vancomycin effect. In conclusion, depletion of vancomycin-sensitive bacteria enhances the antitumor activity of RT, which has important clinical ramifications.
More evidence is needed before general supplementation
Authors: Miles D Witham
Journal: BMJ (2008)

<h3>Background</h3> There is conflicting evidence on the associations between participation in vigorous sports, health habits, familial factors and subsequent mortality. We investigated all-cause mortality and health-related behaviour among former elite athletes and their brothers. <h3>Methods</h3> The mortality of Finnish male former elite athletes, who had represented Finland between 1920 and 1965 (n=900) and their age-matched brothers (n=900), was followed from the time when athlete started an elite athlete career until 31 December 2015. The age-adjusted HRs were calculated by a paired Cox proportional hazards model. In 2001, surviving participants (n=199 athletes and n=199 age-matched brothers) reported their self-rated health (SRH), physical activity, alcohol consumption and smoking habits in the questionnaire. <h3>Results</h3> During the total follow-up period, 1296 deaths (72% of the cohort) occurred. The age-adjusted HRs for all-cause mortality in former athletes was 0.75 (95% CI 0.65 to 0.87, P&lt;0.001) compared with their age-matched brothers. Median age at death was 79.9 years for endurance, 75.9 years for mixed sports and 72.2 years for power sports athletes, and 77.5, 73.7 and 72.2 years for their age-matched brothers, respectively. In 2001, compared with their brothers, former athletes smoked less (P&lt;0.001), were more physically active (P&lt;0.05) and rated their health more often as very good (P&lt;0.05). <h3>Conclusions</h3> Former elite athletes are more physically active, smoke less, have better self-rated health and live longer than their brothers. Genetic differences between athletes and brothers, aerobic training for endurance elite sports and a healthier lifestyle may all contribute to reduced mortality.
Nanotechnology meets atopic dermatitis: Current solutions, challenges and future prospects. Insights and implications from a systematic review of the literature
Authors: Giovanni Damiani, Roberto Eggenhöffner, Paolo Daniele Maria Pigatto, Nicola Luigi Bragazzi
Journal: Bioactive Materials (2019)

Atopic dermatitis is a chronic, relapsing, non-contiguous, exudative eczema/dermatitis, which represents a complex, multi-factorial disorder, due to an impairment of the stratum corneum barrier. Currently available drugs have a low skin bioavailability and may give rise to severe adverse events. Nanotechnologies, including nano-particles, liposomes, nano-gels, nano-mixtures, nano-emulsions and other nano-carriers, offer unprecedented solutions to these issues, enabling: i) the management of different clinical forms of atopic dermatitis, especially the recalcitrant ones, i) a better bio-availability and trans-dermal drug targeted delivery at the inflammation site, ii) dose control, iii) significant improvements both in clinical symptoms and immune responses, iv) with less adverse events being reported and a better safety profile. However, some nano-sized structures could amplify and even worsen symptoms in particularly susceptible individuals. Furthermore, most studies included in the present systematic review have been conducted in-vitro or in-vivo, with few randomized controlled clinical trials (RCTs). Future investigations should adopt this design in order to enable scholars achieving robust findings and evidence. Therefore, given the above-mentioned shortcomings, further research in the field is urgently warranted.
Bortezomib Induces Proliferation of Mesenchymal Progenitor Cells and Promotes Differentiation towards Osteoblastic Lineage.
Authors: Siddhartha Mukherjee, Noopur Raje, Chirayu Patel, Sonia Vallet, Joshua Aronson, Shweta Chhetri, Constantine Mitsiades, Teru Hideshima, Kenneth C. Anderson, David T. Scadden
Journal: Blood (2006)
Comparative analysis of total body irradiation (TBI)-based and non-TBI-based myeloablative conditioning for acute myeloid leukemia in remission with or without measurable residual disease
Authors: Linde M. Morsink, Evandro D. Bezerra, Megan Othus, Brent L. Wood, Min Fang, Brenda M. Sandmaier, Marco B. Mielcarek, H. Joachim Deeg, Gary Schoch, Frederick R. Appelbaum, Roland B. Walter
Journal: Leukemia (2019)
TRIC-A Channel Maintains Store Calcium Handling by Interacting With Type 2 Ryanodine Receptor in Cardiac Muscle
Authors: Xinyu Zhou, Ki Ho Park, Daiju Yamazaki, Pei-hui Lin, Miyuki Nishi, Zhiwei Ma, Liming Qiu, Takashi Murayama, Xiaoqin Zou, Hiroshi Takeshima, Jingsong Zhou, Jianjie Ma
Journal: Circulation Research (2019)

Trimeric intracellular cation (TRIC)-A and B are distributed to endoplasmic reticulum/sarcoplasmic reticulum intracellular Ca2+ stores. The crystal structure of TRIC has been determined, confirming the homotrimeric structure of a potassium channel. While the pore architectures of TRIC-A and TRIC-B are conserved, the carboxyl-terminal tail (CTT) domains of TRIC-A and TRIC-B are different from each other. Aside from its recognized role as a counterion channel that participates in excitation-contraction coupling of striated muscles, the physiological function of TRIC-A in heart physiology and disease has remained largely unexplored.In cardiomyocytes, spontaneous Ca2+ waves, triggered by store overload-induced Ca2+ release mediated by the RyR2 (type 2 ryanodine receptor), develop extrasystolic contractions often associated with arrhythmic events. Here, we test the hypothesis that TRIC-A is a physiological component of RyR2-mediated Ca2+ release machinery that directly modulates store overload-induced Ca2+ release activity via CTT.We show that cardiomyocytes derived from the TRIC-A-/- (TRIC-A knockout) mice display dysregulated Ca2+ movement across sarcoplasmic reticulum. Biochemical studies demonstrate a direct interaction between CTT-A and RyR2. Modeling and docking studies reveal potential sites on RyR2 that show differential interactions with CTT-A and CTT-B. In HEK293 (human embryonic kidney) cells with stable expression of RyR2, transient expression of TRIC-A, but not TRIC-B, leads to apparent suppression of spontaneous Ca2+ oscillations. Ca2+ measurements using the cytosolic indicator Fura-2 and the endoplasmic reticulum luminal store indicator D1ER suggest that TRIC-A enhances Ca2+ leak across the endoplasmic reticulum by directly targeting RyR2 to modulate store overload-induced Ca2+ release. Moreover, synthetic CTT-A peptide facilitates RyR2 activity in lipid bilayer reconstitution system, enhances Ca2+ sparks in permeabilized TRIC-A-/- cardiomyocytes, and induces intracellular Ca2+ release after microinjection into isolated cardiomyocytes, whereas such effects were not observed with the CTT-B peptide. In response to isoproterenol stimulation, the TRIC-A-/- mice display irregular ECG and develop more fibrosis than the WT (wild type) littermates.In addition to the ion-conducting function, TRIC-A functions as an accessory protein of RyR2 to modulate sarcoplasmic reticulum Ca2+ handling in cardiac muscle.
Response to: ‘Association between osteoporosis and statin therapy: the story continues’ by Burden and Weiler
Authors: Michael Leutner, Caspar Matzhold, Luise Bellach, Carola Deischinger, Jürgen Harreiter, Stefan Thurner, Peter Klimek, Alexandra Kautzky-Willer
Journal: Annals of the Rheumatic Diseases (2019)

We have read with great interest the correspondence of Burden and Weiler1 referring to our previously published manuscripts.2 3 First, they sharply observe that the crude OR between the statin group and the matched cohort shows no effect and therefore inquire as to how exactly we adjust for age. In our original study, we grouped patients according to their medications, computed mean age and sex within these medication groups as covariates, and performed a weighted multivariate regression on the risk of osteoporosis within the different medication groups (one ‘observation’ corresponds to one medication group, weighted proportionally to the patients in that group). This grouping by medication was performed for computational convenience due to our large cohort. We confirmed that our results do not qualitatively change if instead of grouping the patients we evaluate a regression model in which each observation is one patient. In response to the correspondence by Burden and Weiler, we have now additionally performed a multivariate regression as reported in the original paper, except that we used the ‘matched …
High-Throughput Microrna Profiling in Patients with Waldenstrom’s Macroglobulinemia.
Authors: Sophia Adamia, Samir B Amin, Cheng Li, Christopher J Patterson, Herve AvetLoiseau, Stephane Minvielle, Philippe Moreau, Kenneth C Anderson, Nikhil C. Munshi, Steven Treon
Journal: Blood (2008)
The High Mobility Group A1 Chromatin Regulator Is Required for Pathologic Megakaryocyte Development and Progression to Myelofibrosis in JAK2V617F Murine Models
Authors: Alison R. Moliterno, Donna Marie Williams, Liping Li, Lingling Xian, Li Luo, Amy S. Duffield, Ophelia Rogers, Jerry L. Spivak, Linda Resar
Journal: Blood (2019)
Distinct Genetic Aberrations in Molecular Subtypes of Diffuse Large B Cell Lymphoma Detected by Array CGH.
Authors: Georg Lenz, George W. Wright, Sandeep Dave, Wenming Xiao, John Powell, Andreas Rosenwald, Hans-Konrad Muller-Hermelink, Randy D. Gascoyne, Joseph M. Connors, Elias Campo, Elaine S. Jaffe, Jan Delabie, Erlend B. Smeland, Lisa Rimsza, Richard I. Fisher, Wing C. Chan, Louis M. Staudt
Journal: Blood (2007)
eIF4A2 drives repression of translation at initiation by Ccr4-Not through purine-rich motifs in the 5′UTR
Authors: Ania Wilczynska, Sarah L. Gillen, Tobias Schmidt, Hedda A. Meijer, Rebekah Jukes-Jones, Claudia Langlais, Kari Kopra, Wei-Ting Lu, Jack D. Godfrey, Benjamin R. Hawley, Kelly Hodge, Sara Zanivan, Kelvin Cain, John Le Quesne, Martin Bushell
Journal: Genome biology (2019)

Abstract Background Regulation of the mRNA life cycle is central to gene expression control and determination of cell fate. miRNAs represent a critical mRNA regulatory mechanism, but despite decades of research, their mode of action is still not fully understood. Results Here, we show that eIF4A2 is a major effector of the repressive miRNA pathway functioning via the Ccr4-Not complex. We demonstrate that while DDX6 interacts with Ccr4-Not, its effects in the mechanism are not as pronounced. Through its interaction with the Ccr4-Not complex, eIF4A2 represses mRNAs at translation initiation. We show evidence that native eIF4A2 has similar RNA selectivity to chemically inhibited eIF4A1. eIF4A2 exerts its repressive effect by binding purine-rich motifs which are enriched in the 5′UTR of target mRNAs directly upstream of the AUG start codon. Conclusions Our data support a model whereby purine motifs towards the 3′ end of the 5′UTR are associated with increased ribosome occupancy and possible uORF activation upon eIF4A2 binding.
Multidimensional Geriatric Assessment for Elderly Patients (≥60 years) Submitted for Allogeneic Stem Cell Transplantation. a French (Paris) - Italian (Brescia) 10-Years Experience on 228 Patients
Authors: Nicola Polverelli, Paolo Tura, Giorgia Battipaglia, Gandolfi Lisa, Tatiana Zollner, Michele Malagola, Enrico Morello, Alessandro Turra, Simona Bernardi, Camilla Zanaglio, Federica Re, Mohamad Mohty, Domenico Russo
Journal: Blood (2019)