tbuckley/cabot-search huggingface dataset:
Pharmacological targeting of CXCL12/CXCR4 signaling in prostate cancer bone metastasis
Authors: M. Katie Conley-LaComb, Louie Semaan, Rajareddy Singareddy, Yanfeng Li, Elisabeth I. Heath, Seongho Kim, Michael L. Cher, Sreenivasa R. Chinni
Journal: Molecular Cancer (2016)

The CXCL12/CXCR4 axis transactivates HER2 and promotes intraosseous tumor growth. To further explore the transactivation of HER2 by CXCL12, we investigated the role of small GTP protein Gαi2 in Src and HER2 phosphorylation in lipid raft membrane microdomains and the significance of CXCR4 in prostate cancer bone tumor growth. We used a variety of methods such as lipid raft isolation, invasion assays, an in vivo model of intratibial tumor growth, bone histomorphometry, and immunohistochemistry to determine the role of CXCR4 signaling in lipid raft membrane microdomains and effects of targeting of CXCR4 for bone tumor growth. We determined that (a) CXCL12/CXCR4 transactivation of EGFR and HER2 is confined to lipid raft membrane microdomains, (b) CXCL12 activation of HER2 and Src is mediated by small GTP proteins in lipid rafts, (c) inhibition of the CXCL12/CXCR4 axis through plerixafor abrogates the initial establishment of tumor growth without affecting the growth of established bone tumors, and (d) inhibition of EGFR signaling through gefitinib leads to inhibition of established bone tumor growth. These data suggest that lipid raft membrane microdomains are key sites for CXCL12/CXCR4 transactivation of HER2 via small GTP binding protein Gαi2 and Src kinase. The initial establishment of prostate cancer is supported by the endosteal niche, and blocking the CXCL12/CXCR4 axis of this niche along with its downstream signaling severely compromises initial establishment of tumors in the bone microenvironment, whereas expanding bone tumors are sensitive only to the members of growth factor receptor inhibition.
Oral Melphalan, Cyclophosfamide and Prednisone (MCP) in 72 Newly Diagnosed Waldenström’s Macroglobulinemia Patients: Results and Costs Analysis.
Authors: Maria Teresa Petrucci, Ombretta Annibali, Anna Levi, Maria C. Tirindelli, Carolina Fossati, Cristiano Gallucci, Patrizia Del Bianco, Franco Mandelli, Giuseppe Avvisati
Journal: Blood (2004)
Dyspnoea perception and susceptibility to exacerbation in COPD
Authors: Heidi A Ridsdale, John R Hurst
Journal: Thorax (2016)

COPD is a heterogeneous condition. This concept has evolved from classic descriptions of pink puffers and blue bloaters to a more complex understanding of disease phenotypes. Phenotypes are relevant because they may predict an important clinical outcome or a specific underlying disease mechanism (endotype), either or both of which might suggest benefit from a particular intervention—‘personalised medicine’. In addition to the progressive decline in lung function, symptoms and physical performance that characterise COPD, (some) patients are prone to periodic deteriorations in respiratory health called exacerbations. And given that exacerbations are responsible for much of the morbidity, mortality and therefore healthcare costs associated with COPD, exacerbation-susceptible patients or ‘frequent exacerbators’ form a clinically relevant phenotype. Why does one patient get more exacerbations than another? A simple clinical question, without a simple answer.

To this first level of complexity in COPD—phenotypes—we must add that exacerbations themselves are hypercapnoea events. Assume, for a moment, that a patient is truly having an exacerbation (and not one of the other pathologies that can cause symptom deterioration in COPD1). That exacerbation might be …
Lumacaftor/Ivacaftor in Patients Aged 6–11 Years with Cystic Fibrosis and Homozygous for <i>F508del-CFTR</i>
Authors: Carlos E. Milla, Felix Ratjen, Gautham Marigowda, Fang Liu, David Waltz, Margaret Rosenfeld
Journal: American Journal of Respiratory and Critical Care Medicine (2017)

Combination lumacaftor/ivacaftor has been shown to improve lung function and other endpoints in patients aged 12 years and older with cystic fibrosis and homozygous for F508del-CFTR, but it has not been assessed in younger patients.
Production of Hollow Bacterial Cellulose Microspheres Using Microfluidics to Form an Injectable Porous Scaffold for Wound Healing
Authors: Jiaqing Yu, Tzu‐Rung Huang, Zhen Han Lim, Rongcong Luo, Rupali Reddy Pasula, Lun‐De Liao, Sierin Lim, Chia‐Hung Chen
Journal: Advanced Healthcare Materials (2016)

Bacterial cellulose (BC) is a biocompatible material with high purity and robust mechanical strength used to fabricate desirable scaffolds for 3D cell culture and wound healing. However, the chemical resistance of BC and its insolubility in the majority of solutions make it difficult to manipulate using standard chemical methods. In this study, a microfluidic process is developed to produce hollow BC microspheres with desirable internal structures and morphology. Microfluidics is used to generate a core–shell structured microparticle with an alginate core and agarose shell as a template to encapsulate Gluconacetobacter xylinus for long‐term static culture. G. xylinus then secretes BC, which becomes entangled within the shell of the structured hydrogel microparticles and forms BC microspheres. The removal of the hydrogel template via thermal‐chemical treatments yields robust BC microspheres exhibiting a hollow morphology. These hollow microspheres spontaneously assemble as functional units to form a novel injectable scaffold. In vitro, a highly porous scaffold is created to enable effective 3D cell culture with a high cell proliferation rate and better depth distribution. In vivo, this injectable scaffold facilitates tissue regeneration, resulting in rapid wound‐healing in a Sprague Dawley rat skin model.
NCO-03NEUROPSYCHOLOGICAL FUNCTIONING IN THE FIRST YEAR FOLLOWING DIAGNOSIS OF PEDIATRIC MEDULLOBLASTOMA: PRELIMINARY RESULTS FROM CHILDREN'S ONCOLOGY GROUP (COG) ACNS0331
Authors: Leanne Embry, Kristina Hardy, Annett Robert, Eugene Hwang, Stephanie Perkins, Jeff Michalski, Robert Noll
Journal: Neuro-Oncology (2015)

BACKGROUND: Cognitive late effects in survivors of medulloblastoma are well-documented; however, the onset and development of domain-specific difficulties have not yet been well-described in large, prospective samples of children. We aimed to examine neuropsychological functioning of children receiving treatment for medulloblastoma on a COG protocol within the first year after diagnosis. METHODS: Children aged 8 and older who were diagnosed with medulloblastoma and treated on COG ACNS0331 were invited to participate in neuropsychological testing as part of the original study design or, later, in conjunction with COG protocol ALTE07C1. All children received 24 Gy of cranial-spinal radiation with a boost either to the tumor bed or to the entire posterior fossa as well as standard chemotherapy. Participants were evaluated at 9 (+ 3) months post-diagnosis with a battery measuring intellectual functioning, processing speed, and working memory. RESULTS: One hundred sixty-one participants (mean age = 12.3, range = 8-20, 61.5% male, 77.6% white) were evaluated. Early medical complications included 19.3% (n = 31) children with cerebellar mutism and 29.8% (n = 48) with treated hydrocephalus. Mean estimated IQ was in the average range, as measured by age-appropriate versions of the Wechsler scales (Mean = 96.4, SD = 15.4). In contrast, processing speed scores were impaired (Mean = 80.3, SD = 13.6). Estimated IQ and processing speed scores were unrelated to baseline demographics; however, slower processing speed was significantly associated with treated hydrocephalus (Treated hydrocephalus M = 73. 3; F = 3.31, p <.05). CONCLUSIONS: Children with medulloblastoma evidenced impaired processing speed in the first year after diagnosis, which was further diminished for children with treated hydrocephalus. Slower processing speed has been linked to reduced white matter volume in children treated with cranial radiation. These deficits may be the first indicator of emerging, treatment-related cognitive late effects.
Outcomes after Rehospitalization at the Same Hospital or a Different Hospital Following Critical Illness
Authors: May Hua, Michelle Ng Gong, Andrea Miltiades, Hannah Wunsch
Journal: American Journal of Respiratory and Critical Care Medicine (2017)

Intensive care unit (ICU) patients who receive mechanical ventilation are at high risk for early rehospitalization. Given the medical complexity of these patients, a lack of continuity of care may adversely affect their outcomes during rehospitalization.To determine whether outcomes differ for patients who are rehospitalized at a different hospital versus the hospital of their index ICU stay.We conducted a retrospective cohort study of mechanically ventilated ICU patients rehospitalized within 30 days in New York State hospitals between 2008 and 2013.We measured frequency of rehospitalization at a different hospital, mortality, length of stay, and costs during rehospitalization. Of 26,947 mechanically ventilated ICU patients rehospitalized within 30 days of discharge, 8,443 (31.3%) were rehospitalized at a different hospital than that of the index ICU stay. For patients at a different hospital, 13.7% died during rehospitalization versus 11.1% who died at the index hospital (adjusted rate ratio [aRR], 1.11; 95% confidence interval [CI], 1.03-1.20; P = 0.009). Patients who died at a different hospital had shorter length of stay (aRR, 0.80; 95% CI, 0.70-0.92; P = 0.001) and decreased costs (adjusted mean difference, -$9,632.73; 95% CI, -$16,387.60 to -$2,877.88; P = 0.005), whereas survivors of rehospitalization at a different hospital had a modest increase in length of stay (aRR, 1.06; 95% CI, 1.01-1.11; P = 0.009) and increased costs of care (adjusted mean difference, $1,665.34; 95% CI, $602.12-$2,728.56; P = 0.002).Almost one-third of mechanically ventilated critically ill patients were rehospitalized at a different hospital than that of the index ICU stay. This care discontinuity was associated with increased mortality.
Abstract 2931: Raised Blood Pressure Modifies the Association between Alcohol Intake and the Progression of Arterial stiffness: An 6 years’ observational study
Authors: Hirofumi Tomiyama, Chisa Matsumoto, Jiko Yamada, Masanobu Yoshida, Kazuki Shiina, Akira Yamashina
Journal: Circulation (2007)

Objectives: The J-shaped association between alcohol intake and cardiovascular events has been reported. Increased arterial stiffness is a cardiovascular risk, and raised blood pressure (RBP) (≥130/85 mmHg) is associated with a progressive increase of arterial stiffness. The present prospective study was conducted to examine the association between alcohol intake and the progression of arterial stiffness, and also clarify whether RBP modify this association over a period of 6 years. Methods : The brachial-ankle PWV was measured and alcohol intake was interviewed on three occasions, at an interval of 3 years, in Japanese male subjects without RBP (n=955) and those with RBP (n=601) (age, 40±8 years, 1279 men and 287 women). Results: According to the results of the interviews on three occasions, the subjects were categorized according to their daily alcohol intake into three groups {non-drinker group (Non), light-moderate (LiMo) and heavy (Heav) alcohol intake groups}. In subjects without RBP, the increase of the PWV during 6 years’ follow-up was lower in the LiMo group than in the Non group, even after adjusting changes in atherosclerotic risk factors (p&lt;0.05); however, no such attenuation was observed in the subjects with RBP. On the other hands, in subjects with RBP, the increase of the PWV during 6 years’ follow-up was higher in the Heav group than in other two groups (Figure ). Conclusion : Light-moderate alcohol intake may have a vasculo-protective effect against structural arterial stiffening in subjects without RBP. In the presence of RBP, however, this protective effect is blunted and heavy alcohol intake seems to be rather harmful in middle-aged subjects.
Australia plans to tighten visa conditions for UK doctors
Authors: Tom Moberly
Journal: BMJ (2016)

Australia’s government has announced plans to restrict applications for working visas from doctors from the United Kingdom and other countries.

Ministers have included nine medical specialties in the list of occupations that they want considered for removal from the country’s list of skilled occupations. The list is used to identify roles where skilled migrants would bring benefits to the Australian economy.

Commenting on the decision, Michael Gannon, president …
Gene Expression Profiling Using the Illumina ‘DASL’ Platform on RNA Extracted From Formalin Fixed Paraffin Embedded (FFPE) Tissue Identifies Distinct Prognostic Groups In CHOP-R Treated DLBCL
Authors: Sharon Barrans, Lisa Worrillow, Matthew Care, Simon Crouch, Alex Smith, Russell Patmore, Andrew Davies, Reuben Tooze, Eve Roman, Andrew Jack
Journal: Blood (2010)
Abstract 4472: Plitidepsin shows antitumor activity in patient-derived tumor xenografts and hematologic malignancies
Authors: Armin Maier, Gerhard Kelter, Vincent Vuaroquaux, Pablo M. Avilés Marin, Carmen Cuevas, Carlos M. Galmarini, Heinz H. Fiebig
Journal: Cancer Research (2015)

Abstract Plitidepsin is a new marine-derived anti-tumor agent, originally isolated from the tunicate Aplidium albicans that is now fully obtained by total chemical synthesis. The compound is currently being evaluated in a pivotal phase III trial in patients with refractory/relapsed multiple myeloma. Previous in vitro studies in 26 hematological cell lines demonstrated that plitidepsin was more active in multiple myeloma and non-Hodgkin lymphoma compared to CML, AML and ALL derived cell lines as determined in a 4 day proliferation assay in suspension cultures. We have recently shown that plitidepsin interacts selectively with eEF1A2 (eukaryotic translation elongation factor 1 alpha 2) in tumor cells, which results in apoptotic cell death. To identify target tumor types for future clinical studies, the inhibition of colony formation of plitidepsin was assessed in vitro in 116 established patient derived xenografts tumor models from 23 different tumor types, including solid tumors and hematological malignancies such as myeloma, leukemia and lymphoma. The anti-tumor activity of plitidepsin varied depending on the concentration used, achieving a mean IC70 (inhibitory concentration of 70%) value of 3 nM (range between 0.03 nM and &amp;gt;1 μM), which can be also achieved in patients treated using the clinical recommended dose or less. 39 out of 116 tumors showed above average sensitivity (IC70 &amp;lt; 1nM) and IC70 values in these tumors were about 9-fold lower than the mean of all tumors as tested. Sensitive tumor types were seen among different tumor types, such as hematological malignancies, pleuramesothelioma, melanoma, small cell and non-small cell lung cancer (both adeno and large cell), as well as renal cancer. In conclusion plitidepsin showed a broad differential antitumor activity in vitro in hematological malignancies and in solid tumors. Bioinformatic analyses are currently underway to identify biomarkers and/or gene signatures that can predict sensitivity or resistance to plitidepsin for selecting patients being responsive to the drug. Citation Format: Armin Maier, Gerhard Kelter, Vincent Vuaroquaux, Pablo M. Avilés Marin, Carmen Cuevas, Carlos M. Galmarini, Heinz H. Fiebig. Plitidepsin shows antitumor activity in patient-derived tumor xenografts and hematologic malignancies. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4472. doi:10.1158/1538-7445.AM2015-4472
The Genotype Combination of the P2Y12 Gene Might Confer Greater Risk for Coronary Artery Disease.
Authors: Koji Isobe, Yumiko Matsubara, Shinichi Takahashi, Toshihiro Uchida, Hiroaki Ishihara, Toshiro Shibano, Mie Ishikawa, Kenichi Matsushita, Shiro Iwanaga, Satosh Ogawa, Gentaro Watanabe, Yasuo Ikeda, Mitsuru Murata
Journal: Blood (2006)
More Rapid Outgrowth Kinetics of BCR-ABL Mutations in Advanced Versus Newly Diagnosed Philadelphia-Positive Acute Lymphoblastic Leukemia (Ph+ ALL): Clinical-Translational Evidence for a Contributory Role of Non-Mutational Resistance Mechanisms.
Authors: Heike Pfeifer, Barbara Wassmann, Silvia Wystub, Patrick Brueck, Andreas Hochhaus, Hubert Serve, Dieter Hoelzer, Oliver Ottmann
Journal: Blood (2007)
Nicotinamide adenine dinucleotide biosynthesis promotes liver regeneration
Authors: Sarmistha Mukherjee, Karthikeyani Chellappa, Andrea Moffitt, Joan Ndungu, Ryan W. Dellinger, James G. Davis, Beamon Agarwal, Joseph A. Baur
Journal: Hepatology (2016)

The regenerative capacity of the liver is essential for recovery from surgical resection or injuries induced by trauma or toxins. During liver regeneration, the concentration of nicotinamide adenine dinucleotide (NAD) falls, at least in part due to metabolic competition for precursors. To test whether NAD availability restricts the rate of liver regeneration, we supplied nicotinamide riboside (NR), an NAD precursor, in the drinking water of mice subjected to partial hepatectomy. NR increased DNA synthesis, mitotic index, and mass restoration in the regenerating livers. Intriguingly, NR also ameliorated the steatosis that normally accompanies liver regeneration. To distinguish the role of hepatocyte NAD levels from any systemic effects of NR, we generated mice overexpressing nicotinamide phosphoribosyltransferase, a rate‐limiting enzyme for NAD synthesis, specifically in the liver. Nicotinamide phosphoribosyltransferase overexpressing mice were mildly hyperglycemic at baseline and, similar to mice treated with NR, exhibited enhanced liver regeneration and reduced steatosis following partial hepatectomy. Conversely, mice lacking nicotinamide phosphoribosyltransferase in hepatocytes exhibited impaired regenerative capacity that was completely rescued by administering NR. Conclusion : NAD availability is limiting during liver regeneration, and supplementation with precursors such as NR may be therapeutic in settings of acute liver injury. (H epatology 2017;65:616‐630).
Mir-21 Is Over Expressed in Aggressive SMZL
Authors: Marie Bouteloup, Aurélie Verney, Lucile Baseggio, Evelyne Callet-Bauchu, Pascale Felman, Martine Ffrench, Bertrand Coiffier, Jean-Pierre Magaud, Francoise Berger, Gilles Andre Salles, Alexandra Traverse-Glehen
Journal: Blood (2008)
P0226 : Reduction in sumoylation-dependent S100A4 nuclear import in cholangiocarcinoma by low dose paclitaxel halts tumor invasiveness and hematogenous metastatization by modulating Rho-A and Cdc42 activities
Authors: G. Spagnuolo, M. Cadamuro, L. Sambado, S. Indraccolo, G. Nardo, A. Rosato, E. Novelli, C. Spirlì, M. Strazzabosco, L. Fabris
Journal: Journal of Hepatology (2015)
Substantially Improved Outcome of Adult Burkitt Non-Hodgkin Lymphoma and Leukemia Patients with Rituximab and a Short-Intensive Chemotherapy; Report of a Large Prospective Multicenter Trial
Authors: Dieter Hoelzer, Jan Walewski, Hartmut Döhner, Mathias Schmid, Wolfgang Hiddemann, Anja Baumann, Hubert Serve, Ulrich Dührsen, Andreas HÃ¼ttmann, Eckhard Thiel, Jolanta Dengler, Michael Kneba, Markus Schuler, Ingo Schmidt-Wolf, Joachim Beck, Bernd Hertenstein, Albrecht Reichle, Katarzyna Domanska-Czyz, Rainer Fietkau, Heinz-August Horst, Harald Rieder, Stefan Schwartz, Thomas Burmeister, Nicola Goekbuget
Journal: Blood (2012)
Strong Correlation of High Endogenous Plasma Levels of Tissue Factor Pathway Inhibitor (TFPI) with Poor Blood Clotting and Corrective Action of BAX 513 Under FVIII-Inhibited Conditions
Authors: Michael Dockal, Monika Gorczyca, Sabine Knappe, Michael Palige, Hartmut J. Ehrlich, Friedrich Scheiflinger, Bernd Jilma
Journal: Blood (2011)
Abstract 15130: Biophysical Effects of a Hyaluronic Acid Based Hydrogel on Average Peak Stress of the Left Ventricular Wall Post Myocardial Infarction
Authors: Eva J Perez, Brendan P Purcell, David C Lobb, Christina M Logdon, Heather Doviak, James A Shuman, Craig P Novack, Kia N Zellars, Sara Pettaway, Joseph H Gorman Iii, Robert C Gorman, Jason A Burdick, Tarek Shazly, Francis G Spinale
Journal: Circulation (2013)

Background: : A common event following a myocardial infarction (MI) is left ventricular (LV) remodeling characterized by mural wall thinning of the MI region and LV dilation, resulting in increased...
Progressive refractory light chain amyloidosis and multiple myeloma patients are responsive to the addition of clarithromycin to IMiD based therapy
Authors: Adir Shaulov, Chezi Ganzel, Noam Benyamini, Yossef Barshay, Neta Goldschmidt, David Lavie, Diana Libster, Alex Gural, Batia Avni, Moshe E. Gatt
Journal: American Journal of Hematology (2016)

Multiple myeloma (MM) and primary systemic light chain amyloidosis (AL) are both chronic plasma cell dyscrasias with different clinical expression but limited treatment options for relapsed refractory disease. We report the effect of the addition of clarithromycin on 31 MM and 17 AL with relapsed or refractory disease who had an insufficient response or disease progression while on an IMiD based therapy. In this high risk population, hematological response was reported in 48% of MM patients and 94% of AL patients. Responses were reported early in both groups (median 35 days) and were more sustained in AL patients. Adverse events were common and included mostly grade 1-2 fatigue, infections and abdominal discomfort. Cytopenias were common and cardiac complications were rare in both MM and AL patients. Clarithromycin-IMiD combination therapy appears to be both effective and safe in progressive MM and primarily in AL patients, although a prospective clinical trial is warranted to validate these results. Am. J. Hematol. 92:131-135, 2017. © 2016 Wiley Periodicals, Inc.
Establishment of a new acute-on-chronic liver failure model
Authors: Fangfang Li, Luyang Miao, Hua Sun, Yuyang Zhang, Xiuqi Bao, Dan Zhang
Journal: Acta Pharmaceutica Sinica B (2016)

To establish an animal model of acute-on-chronic liver failure (ACLF) that would replicate the pathological process of ACLF in humans, rats were administered porcine serum (PS) for 11 weeks. Liver fibrosis was determined by pathological and biochemical assessments. The animals then were injected with d-galactosamine (d-gal) and lipopolysaccharide (LPS). The survival times of animals with cirrhosis and ACLF were determined over 48 h. Other animals were killed at 0, 4, 8 and 12 h after administration of d-gal/LPS. Liver injury was assessed by histopathological analysis and biochemical indices, and apoptosis was detected by Western blot and TUNEL analysis. After PS administration for 11 weeks the serum levels of hyaluronic acid and N-procollagen type III peptide increased significantly, and serious fibrosis and cirrhosis was observed at weeks 10 and 11. Cirrhotic rats were injected with d-gal/LPS to induced ACLF; the rate of mortality over 48 h was 80%. ALT and AST levels increased markedly at 4 h, but decreased significantly at 8 and 12 h post-treatment. The total bilirubin, direct bilirubin, and total bile acids levels increased markedly at 8 and 12 h. Clotting times, TNF-α and IL-6 levels increased significantly, except for 12 h post-treatment. Apoptosis, inflammation and necrosis were elevated as determined by hematoxylin-eosin staining and TUNEL assays. BCL-2 levels decreased significantly, While BAX levels increased significantly. Cytochrome c expression peaked at 8 h post-d-gal/LPS treatment. In conclusion, an ACLF model induced by PS and d-gal/LPS was established and the underlying mechanisms of ACLF development were explored.
VEGF Expression as Prognostic Factor in Early Clinical Stages of Chronic Lymphocytic Leukemia Patients
Authors: Wolney Góis Barreto, Grazziella Curado Siufi, Eliza YS Kimura, Juliana Gilbert Pessoa, Joao Bosco Pesqueiro, Yuri Vasconcelos, Marcal CA Silva, Arlete E Lazar, Mihoko Yamamoto
Journal: Blood (2008)