tbuckley/cabot-search huggingface dataset:
Matriptase Induction of Metalloproteinase‐Dependent Aggrecanolysis In Vitro and In Vivo: Promotion of Osteoarthritic Cartilage Damage by Multiple Mechanisms
Authors: David J. Wilkinson, Angela Habgood, Heather K. Lamb, Paul Thompson, Alastair R. Hawkins, Antoine Désilets, Richard Leduc, Torsten Steinmetzer, Maya Hammami, Melody S. Lee, Charles S. Craik, Sharon Watson, Hua Lin, Jennifer M. Milner, Andrew D. Rowan
Journal: Arthritis & Rheumatology (2017)

To assess the ability of matriptase, a type II transmembrane serine proteinase, to promote aggrecan loss from the cartilage of patients with osteoarthritis (OA) and to determine whether its inhibition can prevent aggrecan loss and cartilage damage in experimental OA.Aggrecan release from human OA cartilage explants and human stem cell-derived cartilage discs was evaluated, and cartilage-conditioned media were used for Western blotting. Gene expression was analyzed by real-time polymerase chain reaction. Murine OA was induced by surgical destabilization of the medial meniscus, and matriptase inhibitors were administered via osmotic minipump or intraarticular injection. Cartilage damage was scored histologically and aggrecan cleavage was visualized immunohistochemically using specific neoepitope antibodies.The addition of soluble recombinant matriptase promoted a time-dependent release of aggrecan (and collagen) from OA cartilage, which was sensitive to metalloproteinase inhibition and protease-activated receptor 2 antagonism. Although engineered human (normal) cartilage discs failed to release aggrecan following matriptase addition, both matrix metalloproteinase- and aggrecanase-mediated cleavages of aggrecan were detected in human OA cartilage. Additionally, while matriptase did not directly degrade aggrecan, it promoted the accumulation of low-density lipoprotein receptor-related protein 1 (LRP-1) in conditioned media of the OA cartilage explants. Matriptase inhibition via neutralizing antibody or small molecule inhibitor significantly reduced cartilage damage scores in murine OA, which was associated with reduced generation of metalloproteinase-mediated aggrecan cleavage.Matriptase potently induces the release of metalloproteinase-generated aggrecan fragments as well as soluble LRP-1 from OA cartilage. Therapeutic targeting of matriptase proteolytic activity reduces metalloproteinase activity, further suggesting that this serine proteinase may have potential as a disease-modifying therapy in OA.
Letter to the editor: Australian immunisation registers: established foundations and opportunities for improvement
Authors: S L Sheridan, S B Lambert
Journal: Eurosurveillance (2012)

Preview this article: Letter to the editor: Australian immunisation registers: established foundations and opportunities for improvement, Page 1 of 1 < Previous page | Next page > /docserver/preview/fulltext/eurosurveillance/17/21/art20177-en-1.gif
Galectin-1 (Gal-1) expression as a prognostic factor in a homogenous cohort of glioblastoma (GB) (Gliocat study)
Authors: N. Vilariño Quintela, N. Martinez Bosch, C. Balana, F. Alameda, A. Estival, E. Pineda, S. Del Barco, M. Gil-Gil, C. Mesia, O. Gallego, C. Carrato, T. Ribalta, N. Vidal, N. Dela Iglesia, O. Arpi, J. Capellades, N. Garcia, J.M. Velarde, P. Navarro, M. Martinez-Garcia
Journal: Annals of Oncology (2017)
Differential Regulation of Evoked and Spontaneous Release by Presynaptic NMDA Receptors
Authors: Therése Abrahamsson, Christina You Chien Chou, Si Ying Li, Adamo Mancino, Rui Ponte Costa, Jennifer Anne Brock, Erin Nuro, Katherine Anne Buchanan, Dale Elgar, Arne Vladimir Blackman, Adam Tudor-Jones, Julia Oyrer, William Todd Farmer, Keith Kazuo Murai, Per Jesper Sjöström
Journal: Neuron (2017)
mFOLFOXIRI + Panitumumab versus FOLFOXIRI as first-line treatment in patients with RAS wild- type metastatic colorectal cancer m(CRC): a randomized phase II VOLFI trial of the AIO (AIO- KRK0109)
Authors: M. Geissler, T. Klingler, J. Riera-Knorrenschield, A. Tannapfel, T. Seufferlein, S. Held, A. Florschütz, S. Kanzler, V. Heinemann, A. Reinacher-Schick, U. Martens
Journal: Annals of Oncology (2018)

Introduction: Triple chemotherapy with an anti-EGFR reported promising activity with some safety concerns in single arm phase II trials. This trial evaluated activity and safety of mFOLFOXIRI + panitumumab vs FOLFOXIRI in ECOG 0-1, primarily non-resectable mCRC patients. Methods: Prospective 2:1 randomized, multi-center, phase II trial comparing mFOLFOXIRI (Ox 85 mg/m2, Iri 150 mg/m2, 5-FU 3000mg/m2 cont. 48h, LV 200 mg/m2) + panitumumab 6 mg/KG (arm A) with FOLFOXIRI (Ox 85 mg/m2, Iri 165 mg/m2, 5-FU 3200mg/m2 cont. 48h, LV 200 mg/m2; arm B), both arms q2w. Cohort 1: irresectable mCRC; cohort 2: chance of secondary resection of metastatic lesions. Primary endpoint was ORR, secondary endpoints were secondary resection rate (cohort 2), DCR, PFS, OS, toxicity, quality of life (QLQ-C30). Financially supported by an unrestricted grant from Amgen. Results: A total of 96 patients were randomized (63 arm A, 33 arm B). ORR was 85.7% in arm A and 54.5% in arm B (p = 0.0013, OR 5.000; 95%-CI 1.870-13.370). DCR was 96.8% in arm A and 78.8% in arm B (p = 0.0071, OR 8.212). ORR in Arm A was 90.6% versus 60.0% (p = 0.0288, OR 6.400) and in Arm B 60.0% versus 50% (p = n.s.) for left and right located CRC, respectively. ORR between arms A and B comparing left and right sided CRC was 90.6% versus 60.0% (p = 0.0039, OR 6.400; 95%-CI 1.889- 21.679) and 60.0% versus 50.0% (p = n.s.), respectively. Secondary resections in cohort 2 were 60% (n = 12) and 36.4% (n = 4) in arms A and B, respectively. Treatment related serious adverse advents grade 3-5 occurred in 32.8% and 12.1% in arms A and B, respectively (p = 0.0297). Nevertheless, no differences in global health status, functional scales, and symptom scales were reported. Conclusion: mFOLFOXIRI plus panitumumab results in significantly higher response rates compared to FOLFOXIRI in RAS wild-type mCRC. Strong effectivity was observed also in right sided and BRAF mutated CRC. High secondary resection rates could be achieved. Although toxicity (treatment related SAEs) was increased, QL reporting was similar in both arms. Final PFS, AEs, and dosing data will be presented at the meeting.
Epithelial-Cell-Derived Phospholipase A 2 Group 1B Is an Endogenous Anthelmintic
Authors: Lewis J. Entwistle, Victoria S. Pelly, Stephanie M. Coomes, Yashaswini Kannan, Jimena Perez-Lloret, Stephanie Czieso, Mariana Silva dos Santos, James I. MacRae, Lucy Collinson, Abdul Sesay, Nikolay Nikolov, Amina Metidji, Helena Helmby, David Y. Hui, Mark S. Wilson
Journal: Cell Host & Microbe (2017)

Highlights•Pla2g1b expression correlated with resistance to intestinal helminth infection•PLA2g1B is essential for resistance to intestinal helminth infection in mice•PLA2g1B directly reduces phospholipid abundance in infective larvae•Pla2g1b is expressed by epithelial cells and is negatively regulated by IL-4RαSummaryImmunity to intestinal helminth infections has been well studied, but the mechanism of helminth killing prior to expulsion remains unclear. Here we identify epithelial-cell-derived phospholipase A2 group 1B (PLA2g1B) as a host-derived endogenous anthelmintic. PLA2g1B is elevated in resistant mice and is responsible for killing tissue-embedded larvae. Despite comparable activities of other essential type-2-dependent immune mechanisms, Pla2g1b−/− mice failed to expel the intestinal helminths Heligmosomoides polygyrus or Nippostrongylus brasiliensis. Expression of Pla2g1b by epithelial cells was dependent upon intestinal microbiota, adaptive immunity, and common-gamma chain-dependent signaling. Notably, Pla2g1b was downregulated in susceptible mice and inhibited by IL-4R-signaling in vitro, uncoupling parasite killing from expulsion mechanisms. Resistance was restored in Pla2g1b−/− mice by treating infective H. polygyrus L3 larvae with PLA2g1B, which reduced larval phospholipid abundance. These findings uncover epithelial-cell-derived Pla2g1b as an essential mediator of helminth killing, highlighting a previously overlooked mechanism of anti-helminth immunity.Graphical abstract
Modulation of Navitoclax Sensitivity by Dihydroartemisinin-Mediated MCL-1 Repression in BCR-ABL+ B-Lineage Acute Lymphoblastic Leukemia
Authors: Amit Budhraja, Meghan E. Turnis, Michelle L. Churchman, Anisha Kothari, Xue Yang, Haiyan Xu, Ewa Kaminska, John C. Panetta, David Finkelstein, Charles G. Mullighan, Joseph T. Opferman
Journal: Clinical Cancer Research (2017)

Abstract Purpose: BCR-ABL+ B-ALL leukemic cells are highly dependent on the expression of endogenous antiapoptotic MCL-1 to promote viability and are resistant to BH3-mimetic agents such as navitoclax (ABT-263) that target BCL-2, BCL-XL, and BCL-W. However, the survival of most normal blood cells and other cell types is also dependent on Mcl-1. Despite the requirement for MCL-1 in these cell types, initial reports of MCL-1–specific BH3-mimetics have not described any overt toxicities associated with single-agent use, but these agents are still early in clinical development. Therefore, we sought to identify approved drugs that could sensitize leukemic cells to ABT-263. Experimental Design: A screen identified dihydroartemisinin (DHA), a water-soluble metabolite of the antimalarial artemisinin. Using mouse and human leukemic cell lines, and primary patient-derived xenografts, the effect of DHA on survival was tested, and mechanistic studies were carried out to discover how DHA functions. We further tested in vitro and in vivo whether combining DHA with ABT-263 could enhance the response of leukemic cells to combination therapy. Results: DHA causes the downmodulation of MCL-1 expression by triggering a cellular stress response that represses translation. The repression of MCL-1 renders leukemic cells highly sensitive to synergistic cell death induced by ABT-263 in a mouse model of BCR-ABL+ B-ALL both in vitro and in vivo. Furthermore, DHA synergizes with ABT-263 in human Ph+ ALL cell lines, and primary patient-derived xenografts of Ph+ ALL in culture. Conclusions: Our findings suggest that combining DHA with ABT-263 can improve therapeutic response in BCR-ABL+ B-ALL. Clin Cancer Res; 23(24); 7558–68. ©2017 AACR.
A novel CpG panel is independently associated with colorectal cancer survival
Authors: M. Jia, Y. Zhang, L. Jansen, V. Walter, D. Edelmann, M. Maierthaler, K. Tagscherer, W. Roth, M. Bewerunge-Hudler, E. Herpel, M. Kloor, A. Ulrich, B. Burwinkel, H. Bläker, J. Chang-Claude, H. Brenner, M. Hoffmeister
Journal: Annals of Oncology (2017)
Modified epirubicin and oxaliplatin plus capecitabine (EOX) Regimen as second-line therapy after failure of modiﬁed docetaxel and cisplatin plus fuorouracil (DCF) regimen in advanced gastric cancer
Authors: Y. Bozkaya, O. Yazici, N. Ozdemir, G.U. Erdem, N.S. Demirci, N. Zengin
Journal: Annals of Oncology (2017)
Hereditary stomatocytosis: An underdiagnosed condition
Authors: Immacolata Andolfo, Roberta Russo, Antonella Gambale, Achille Iolascon
Journal: American Journal of Hematology (2017)

Abstract Hereditary stomatocytoses are a wide class of hemolytic anemias characterized by alterations of ionic flux with increased cation permeability that results in inappropriate shrinkage or swelling of the erythrocytes, and water lost or gained osmotically. The last few years have been crucial for new acquisitions in this field in terms of identifying new causative genes and of studying their pathogenetic mechanisms. This review summarizes the main features of erythrocyte membrane transport diseases, dividing them into forms with either isolated erythroid phenotype (nonsyndromic) or extra‐hematological manifestations (syndromic), and focusing particularly on the most recent advances regarding dehydrated forms of hereditary stomatocytosis and familial pseudohyperkalemia.
An open-label, multicohort, phase 1/2 study in patients with virus-associated cancers (CheckMate 358): Safety and efficacy of neoadjuvant nivolumab in squamous cell carcinoma of the head and neck (SCCHN)
Authors: R.L. Ferris, A. Gonçalves, S.S. Baxi, U.M. Martens, H. Gauthier, M. Langenberg, W.C. Spanos, R.S. Leidner, H. Kang, J. Russell, S. Chiosea, I. Soumaoro, S. Rao, Z.A. Cao, S. Topalian
Journal: Annals of Oncology (2017)
Eltrombopag, Low-Dose Rituximab, and High-Dose Dexamethasone Combination for Patients with Newly Diagnosed Immune Thrombocytopenia: A Pilot "Total Therapy" Study
Authors: David Gomez-Almaguer, Olga Cantu-Rodriguez, Cesar Homero Gutierrez-Aguirre, Jose Carlos Jaime-Perez, Luz C. Tarin-Arzaga, Monica Sanchez Cardenas, Rosa Elena Lozano-Morales, Guillermo Sotomayor Duque, Daniela Cárdenas-Araujo, Andres Gomez-de Leon, Paola Santana-Hernandez, Perla Rocío Colunga-Pedraza
Journal: Blood (2016)
Which Anti-CD20 Antibody Is Better in Follicular Lymphoma?
Authors: James O. Armitage, Dan L. Longo
Journal: New England Journal of Medicine (2017)

Rituximab changed the treatment of patients with follicular lymphoma. When added to standard chemotherapy regimens, it increased the response rate and the complete remission rate.1,2 Rituximab has often been administered as maintenance therapy after a remission that was induced either by single-agent rituximab or by rituximab combined with standard chemotherapy drugs, and it has been shown to prolong the duration of remission.3,4 Since 2000, when rituximab became widely available, survival among patients with low-grade follicular lymphoma has increased from a median of approximately 10 years to a median of approximately 15 to 20 years.5,6 In this issue of the Journal, . . .
Epidémie de rougeole chez des adultes au nord-ouest de la Grèce
Authors: G Mantzios, M Mastora, E Liapis, I Giannakakis, N K Akritidis
Journal: Eurosurveillance (1997)

L'incidence globale de la rougeole en Grece a diminue de facon notable apres l'introduction de la vaccination (sans que des donnees precises soient disponibles) mais des epidemies surviennent encore sporadiquement. En 1965, le vaccin monovalent contre la rougeole etait introduit en Grece puis remplace, en 1989, par le vaccin triple Rougeole Oreillons Rubeole (ROR). Les infections touchent presque toujours les jeunes enfants, mais on peut trouver des cas chez les adultes.
Phase II trial of AZD9291 in second line treatment after acquired resistance with T790M mutation detected from circulating tumor DNA (LiquidLung-O-Cohort 2)
Authors: Y-C. Kim, C.K. Park, I-J. Oh, J-H. Lim, Y-D. Choi, H. Cho, S-J. Ahn, S-Y. Song, J.S. Yun, K-J. Na
Journal: Annals of Oncology (2017)
Improving Assessment of Drug Safety Through Proteomics
Authors: Stephen A. Williams, Ashwin C. Murthy, Robert K. DeLisle, Craig Hyde, Anders Malarstig, Rachel Ostroff, Sophie J. Weiss, Mark R. Segal, Peter Ganz
Journal: Circulation (2017)

Early detection of adverse effects of novel therapies and understanding of their mechanisms could improve the safety and efficiency of drug development. We have retrospectively applied large-scale proteomics to blood samples from ILLUMINATE (Investigation of Lipid Level Management to Understand its Impact in Atherosclerotic Events), a trial of torcetrapib (a cholesterol ester transfer protein inhibitor), that involved 15 067 participants at high cardiovascular risk. ILLUMINATE was terminated at a median of 550 days because of significant absolute increases of 1.2% in cardiovascular events and 0.4% in mortality with torcetrapib. The aims of our analysis were to determine whether a proteomic analysis might reveal biological mechanisms responsible for these harmful effects and whether harmful effects of torcetrapib could have been detected early in the ILLUMINATE trial with proteomics.A nested case-control analysis of paired plasma samples at baseline and at 3 months was performed in 249 participants assigned to torcetrapib plus atorvastatin and 223 participants assigned to atorvastatin only. Within each treatment arm, cases with events were matched to controls 1:1. Main outcomes were a survey of 1129 proteins for discovery of biological pathways altered by torcetrapib and a 9-protein risk score validated to predict myocardial infarction, stroke, heart failure, or death.Plasma concentrations of 200 proteins changed significantly with torcetrapib. Their pathway analysis revealed unexpected and widespread changes in immune and inflammatory functions, as well as changes in endocrine systems, including in aldosterone function and glycemic control. At baseline, 9-protein risk scores were similar in the 2 treatment arms and higher in participants with subsequent events. At 3 months, the absolute 9-protein derived risk increased in the torcetrapib plus atorvastatin arm compared with the atorvastatin-only arm by 1.08% (P=0.0004). Thirty-seven proteins changed in the direction of increased risk of 49 proteins previously associated with cardiovascular and mortality risk.Heretofore unknown effects of torcetrapib were revealed in immune and inflammatory functions. A protein-based risk score predicted harm from torcetrapib within just 3 months. A protein-based risk assessment embedded within a large proteomic survey may prove to be useful in the evaluation of therapies to prevent harm to patients.URL: https://www.clinicaltrials.gov. Unique identifier: NCT00134264.
Association Between Urinary Sodium and Potassium Excretion and Blood Pressure Among Adults in the United States
Authors: Sandra L. Jackson, Mary E. Cogswell, Lixia Zhao, Ana L. Terry, Chia-Yih Wang, Jacqueline Wright, Sallyann M. Coleman King, Barbara Bowman, Te-Ching Chen, Robert Merritt, Catherine M. Loria
Journal: Circulation (2017)

Higher levels of sodium and lower levels of potassium intake are associated with higher blood pressure. However, the shape and magnitude of these associations can vary by study participant characteristics or intake assessment method. Twenty-four-hour urinary excretion of sodium and potassium are unaffected by recall errors and represent all sources of intake, and were collected for the first time in a nationally representative US survey. Our objective was to assess the associations of blood pressure and hypertension with 24-hour urinary excretion of sodium and potassium among US adults.Cross-sectional data were obtained from 766 participants age 20 to 69 years with complete blood pressure and 24-hour urine collections in the 2014 National Health and Nutrition Examination Survey, a nationally representative survey of the US noninstitutionalized population. Usual 24-hour urinary electrolyte excretion (sodium, potassium, and their ratio) was estimated from ≤2 collections on nonconsecutive days, adjusting for day-to-day variability in excretion. Outcomes included systolic and diastolic blood pressure from the average of 3 measures and hypertension status, based on average blood pressure ≥140/90 and antihypertensive medication use.After multivariable adjustment, each 1000-mg difference in usual 24-hour sodium excretion was directly associated with systolic (4.58 mm Hg; 95% confidence interval [CI], 2.64-6.51) and diastolic (2.25 mm Hg; 95% CI, 0.83-3.67) blood pressures. Each 1000-mg difference in potassium excretion was inversely associated with systolic blood pressure (-3.72 mm Hg; 95% CI, -6.01 to -1.42). Each 0.5 U difference in sodium-to-potassium ratio was directly associated with systolic blood pressure (1.72 mm Hg; 95% CI, 0.76-2.68). Hypertension was linearly associated with progressively higher sodium and lower potassium excretion; in comparison with the lowest quartile of excretion, the adjusted odds of hypertension for the highest quartile was 4.22 (95% CI, 1.36-13.15) for sodium, and 0.38 (95% CI, 0.17-0.87) for potassium (P<0.01 for trends).These cross-sectional results show a strong dose-response association between urinary sodium excretion and blood pressure, and an inverse association between urinary potassium excretion and blood pressure, in a nationally representative sample of US adults.
Lutetium-177 PSMA (LuPSMA) theranostics phase II trial: Efficacy, safety and QoL in patients with castrate-resistant prostate cancer treated with LuPSMA
Authors: M.S. Hofman, S. Sandhu, P. Eu, J. Price, T. Akhurst, A. Iravani, G. Kong, A. Ravi-Kumar, S. Williams, S-P. Thang, D. Murphy, M. Scalzo, R.J. Hicks, J. Violet
Journal: Annals of Oncology (2017)
Multidisciplinary team management in head and neck cancer: The real life experience
Authors: J-B. Guy, Y. Xia, A. Vallard, S. Espenel, J-C. Trone, J. Langrand-Escure, A. Hamrouni, M. Ben Mrad, C. Rancoule, S. Ouni, T. Muron, P. Fournel, N. Magne
Journal: Annals of Oncology (2017)
All.Can initiative: improving efficiency in cancer care
Authors: M.S. Aapro, S. Chrostowski, F. Florindi, B. Gandouet, S. Hanna, R. Hazarika, R. Hess, F. de Lorenzo, V. Muthu, K. Oliver, A. Roediger, T. Rosvall-Puplett, B. Ryll, G. Spurrier, K. Steinmann, T. Szucs, S. Wait, L. Wierinck, W. Yared
Journal: Annals of Oncology (2017)
Predictive biomarkers for hyper-progression (HP) in response to immune checkpoint inhibitors (ICI) – analysis of somatic alterations (SAs)
Authors: A.K. Singavi, S. Menon, D. Kilari, A. Alqwasmi, P.S. Ritch, J.P. Thomas, A.L. Martin, C. Oxencis, S. Ali, B. George
Journal: Annals of Oncology (2017)
An Early American Smallpox Vaccine Based on Horsepox
Authors: Livia Schrick, Simon H Tausch, P Wojciech Dabrowski, Clarissa R Damaso, José Esparza, Andreas Nitsche
Journal: New England Journal of Medicine (2017)

Global eradication of smallpox was driven by the development of the smallpox vaccine. In this report, light is shed on the origins of the vaccinia virus.