tbuckley/cabot-search huggingface dataset:
Phosphoproteomic profiling of mouse primary HSPCs reveals new regulators of HSPC mobilization
Authors: Leo D. Wang, Scott B. Ficarro, John N. Hutchinson, Roland Csepanyi-Komi, Phi T. Nguyen, Eva Wisniewski, Jessica Sullivan, Oliver Hofmann, Erzsebet Ligeti, Jarrod A. Marto, Amy J. Wagers
Journal: Blood (2016)
Identification of a microRNA (miRNA) based signature for survival in advanced non-small cell lung cancer (NSCLC) patients (pts) treated with cisplatin-vinorelbine: A ELCWP study.
Authors: Thierry Berghmans, Luc Willems, Marianne Paesmans, Lieveke Ameye, Jean-Jacques Lafitte, Anne-Pascale Meert, Arnaud Scherpereel, Ingrid CsToth, Alexis B. Cortot, Celine Mascaux, Nathalie Leclercq, Jean Paul Sculier
Journal: Journal of Clinical Oncology (2012)

e18006 Background: Main prognostic factors for survival in NSCLC pts are stage and performance status (PS) while sex, histology and others are reported. However, these variables do not allow predicting individual prognosis, justifying further research. MiRNA are small non-coding RNAs regulating gene expression. As a secondary aim of a prospective study, we looked at the prognostic value of tumour miRNA on survival in NSCLC pts treated by cisplatin (60 mg/m 2 D1) and vinorelbine (25 mg/m 2 , D1+8) 1 st line chemotherapy. Methods: During the diagnostic bronchoscopy, a biopsy was lysed into Tripure Isolation Reagent (Roche Diagnostics) on ice, snap frozen and stored at -80°C. MiRNA expression was assessed using TaqMan Low Density Arrays (756 human miRNA panel, Applied Biosystems) and normalized using the delta delta CT method to RNU48 (SNORD48) CT value for every sample. Survival was measured from the registration date. Results: The main characteristics of 38 eligible pts were: median age 60 years, male 27 (71%), 80-100 Karnofsky PS in 26 (68%), adenocarcinoma 20 (53%), stage IV 30 (79%). At time of analysis, 25 pts were dead. After stepwise selection among 756 analysed miRNA, a combination of 4 miRNA including miR-200c, miR-424, miR-29c and miR-124 provided a prognostic signature for survival. Using a linear combination of the miRNA CT values with Cox's regression coefficients as weights, we constructed a prognostic score. With a cut-off of 52, the signature distinguished pts with good (n = 18) and poor (n = 20) prognosis with respective median survival of 47.3 months (95% CI 29.8-52.4) and 15.5 months (95% CI 9.1-22.8) (p &lt;0.001; hazard ratio 21.1, 95% CI 4.7-94.9). The same signature discriminated pts with “good progression-free survival” (median 19.8 months; 95% CI 15.3-33.8) from the others (median 9.1 months; 95% CI 6.3-15.5) (p &lt;0.001; hazard ratio 3.8, 95% CI 1.7-8.7). Conclusions: A 4 miRNA signature is associated with improved survival in patients with advanced stage NSCLC treated with 1 st line cisplatin and vinorelbine. These results need confirmation in an independent cohort and the signature has to be compared to conventional prognostic factors.
Correlation of mast cells positive to tryptase and protease-activated receptor-2 expression and microvascular density in breast cancer patients.
Authors: G. Ranieri, G. Gadaleta-Caldarola, A. Catino, R. Patruno, V. Goffredo, P. Valerio, A. Misino, M. Ammendola, G. De Sarro, C. Gadaleta
Journal: Journal of Clinical Oncology (2010)

e21032 Background: Tryptase, a serine protease stored and released from mast cells (MCs) granules has been identified as a new nonclassical angiogenetic factor and it is an agonist of the proteinase-activated receptor-2 (PAR-2). We have evaluated the correlations between the number of MCs positive to tryptase (MCDPT), the number of breast cancer cells positive to PAR-2 (BC-PAR-2) and microvascular density (MVD) in a series of 97 primary T1-3, N0-2 M0 female breast cancer by means of immunohistochemistry and image analysis methods. Methods: Six-micrometers thick serial sections of formalin-fixed and paraffin-embedded bioptic tumor samples were microwaved at 500 W for 10 min. and treated with a 3% hydrogen peroxide solution. Sections were incubated with primary antibodies: monoclonal antitryptase (AA1; Dako, Glostrup, Denmark), polyclonal anti PAR-2 (N-19; sc-8206 Santa Cruz Biotecnology), and monoclonal anti-CD34 (QB-END 10; Bio-Optica Milan, Italy). Biotinylated secondary antibody, avidin-biotin peroxidase complex, and 3-amino-9-ethylcarbazole were in turn utilised. In serial sections “hot spots” were selected and individual vessels, single tryptase-positive MCs and breast cancer cells positive to PAR-2 were counted by means of image analysis at x400. Results: Data demonstrated a significantly (r = ranging from 0.71 to 0.87; p: ranging from 0.001 to 0.003 by Pearson's analysis respectively) correlation between MCDPT, BC-PAR-2 and MVD to each other. No correlation concerning MCDPT, BC-PAR-2, MVD and the main clinical pathological features was found. Conclusions: Published in vitro data suggest that tryptase may increase capillary growth and endothelial cell proliferation by activation of PAR-2. According to these data we shown that MCDPT, PAR-2 and MVD paralleled to each other suggesting a role in in vivo breast cancer angiogenesis. In this context several tryptase inhibitors such as gabexate mesilate and nafamostat mesilate might be evaluated in clinical trials as a new antiangiogenetic drugs. No significant financial relationships to disclose.
Oncogenic Kras-mediated resistance to chemotherapy via increased ADAM17 activity and ligand shedding in colorectal cancer.
Authors: S. Van Schaeybroeck, J. Kyula, D. Longley, P. Johnston
Journal: Journal of Clinical Oncology (2010)

e14104 Background: Oncogenic mutations in the small GTPase c-Kirsten (K)-ras occur in 40%-45% of patients with advanced colorectal cancer (CRC) and are challenging in development of anti-cancer therapeutics. Clear understanding of the vulnerabilities of Kras mutant (MT) CRC is important, and identification of druggable targets uniquely required by KrasMT CRC cells has the potential to fill a gap in the therapeutic armamentarium of advanced CRC. In this study, we examined the role of mutant Kras in determining response to chemotherapy using isogenic KrasMT HCT116 and Kras wild type (WT) HKH-2 cells. Methods: In vitro and in vivo models of CRC were assessed. ADAM-17 activity was measured using a fluorometric assay. Ligand shedding was assessed by ELISA or Western blotting. Apoptosis was assessed by flow cytometry and Western blotting. Results: HKH-2 cells showed enhanced sensitivity to 5-FU compared to HCT116 cells. Furthermore, oncogenic Kras was associated with increased Erk1/2 activity, ligand shedding and this correlated with increase in ADAM17 activity. Treatment of CRC cells with Kras siRNA, MEK1/2 or Erk1/2 inhibition resulted in inhibition of ligand shedding and ADAM17 activity following chemotherapy treatment and led to a potent increase in apoptosis when combined with chemotherapy in KrasMT cells. In addition, MEK1/2 inhibition resulted in significant decrease in tumour ADAM17 activity and serum ligand shedding and suppressed the growth of HCT116 xenografts. Importantly, we found that apoptosis induced by MEK1/2 inhibition was dependent on ADAM17 activity and ligand shedding. Conclusions: Taken together, our findings indicate that oncogenic Kras regulates chemotherapy resistance via increase in ADAM17 activity and ligand shedding. Furthermore, KrasMT CRC tumours are vulnerable to MEK1/2 inhibitors whose sensitivity is dependent on ADAM17 activity. Moreover, serum ligand levels may be a surrogate marker for response to MEK1/2 inhibition in combination with chemotherapy in Kras MT CRC tumours. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration AstraZeneca
2016 international consensus on femoroacetabular impingement syndrome: the Warwick Agreement—why does it matter?
Authors: Joanne L Kemp, Ian Beasley
Journal: British Journal of Sports Medicine (2016)

Femoroacetabular impingement syndrome (FAIS) is a common cause of hip pain in young and middle-aged adults. It is one of the hot topics in sports medicine, and debate among surgeons, sports physicians and physiotherapists is ongoing. The rate of diagnosis and treatment of FAIS has exploded in the past decade, with rates of hip arthroscopy increasing by almost 400% over this time.1 ,2 Such a rapid increase in diagnosis and treatment can inevitably lead to a backlash, with claims by sceptics of overdiagnosis, over treatment and a lack of evidence. While there may be some truth in these claims, such scepticism can cause people to question whether FAIS exists. Given this, it is important to understand what FAIS is, whether it is a problem and why we need a consensus statement.

FAIS refers to the intra-articular pathology and subsequent symptoms and signs that develop in susceptible individuals when the femoral and acetabular components of the hip repetitively and prematurely abut against each other.3 ,4 Typically, …
Abstract 9904: Trends in Enrollment, Patient Characteristics, Treatments and Outcomes of Older Adults With Non-ST-segment Elevation Acute Coronary Syndromes (ACS) in Clinical Trials
Authors: Gwen M Bernacki, Karen P Alexander, L. Kristin Newby, Qinghong Yang, Phillip Schulte, Harvey D White, E. Magnus Ohman, Kenneth W Mahaffey, Bimal R Shah, Robert P Giugliano, Paul W Armstrong, Robert A Harrington, Pierluigi Tricoci, Frans Van de Werf, John Alexander, Robert M Califf, Renato D Lopes
Journal: Circulation (2013)

Introduction: Whereas individuals aged ≥75 years account for &gt;1/3 of non-ST-segment elevation (NSTE) ACS episodes and the majority of deaths due to NSTE ACS in current practice, little is known about their participation in NSTE ACS clinical trials. Methods: We studied 79,133 NSTE ACS patients enrolled in 11 phase III clinical trials (GUSTO IIb, PURSUIT, PARAGON-A, PARAGON-B, PRISM, PRISM-PLUS, GUSTO IV-ACS, SYNERGY, EARLY ACS, TRACER, APPRAISE-2) during 5 time periods (1994-97, 1998-01, 2002-05, 2006-10) over 17 years. We characterized the population according to age, patient characteristics, medical therapy, and outcomes (severe bleeding, 30-day mortality, 6-month mortality, 30-day composite of death or MI) and examined changes in these parameters over time. Results: Overall, 19.7% of patients enrolled in the selected trials were aged ≥75 years; while this proportion increased during the 1998-01 and 2002-05 periods, it declined in 2006-10 (Table). The prevalence of comorbidities varied (Table). Use of evidence-based medications at discharge among patients aged ≥75 years increased overall (aspirin 66.6 to 93.5%; beta-blockers 40.9 to 78.2%; thienopyridines 5.8 to 76.9%, lipid-lowering drugs 8.0 to 83.4%, ACE inhibitors 24.6 to 62.6% in 1994-97 to 2006-10). 30-day and 6-month mortality consistently declined. During the interval between 1994-97 and 2006-10, severe bleeding and the 30-day composite of death or MI for patients aged ≥75 years declined overall (2.0% to 1.6% for severe bleeding, and 17.6% to 9.3% for composite of 30-day death or MI). Conclusions: Despite significant improvements in clinical care and outcomes among patients aged ≥75 years, their enrollment in NSTE ACS clinical trials is not representative of the NSTE ACS population. Representative enrollment of elderly patients in clinical trials constitutes a critical unmet need to advance their evidence-based care and apply more novel approaches to lower morbidity and mortality.
Bortezomib in Combination with Dexamethasone and Pegylated Liposomal Doxorubicin (DoVeD) Breaks Plateau Responses Following Initial Induction Therapy in Multiple Myeloma: Results of a Phase II Pilot Study.
Authors: Megan C. Manco, Tomer Mark, David S Jayabalan, Faiza Zafar, Roger Pearse, Mary Crann, John P. Leonard, Selina Chen-Kiang, Morton Coleman, Ruben Niesvizky
Journal: Blood (2009)
PICASSO III: A Phase III, Placebo-Controlled Study of Doxorubicin With or Without Palifosfamide in Patients With Metastatic Soft Tissue Sarcoma
Authors: Christopher W. Ryan, Ofer Merimsky, Mark Agulnik, Jean-Yves Blay, Scott M. Schuetze, Brian A. Van Tine, Robin L. Jones, Anthony D. Elias, Edwin Choy, Thierry Alcindor, Vicki L. Keedy, Damon R. Reed, Robert N. Taub, Antoine Italiano, Xavier Garcia del Muro, Ian R. Judson, Jill Y. Buck, Francois Lebel, Jonathan J. Lewis, Robert G. Maki, Patrick Schöffski
Journal: Journal of Clinical Oncology (2016)

Purpose Palifosfamide is the active metabolite of ifosfamide and does not require prodrug activation, thereby avoiding the generation of toxic metabolites. The PICASSO III trial compared doxorubicin plus palifosfamide with doxorubicin plus placebo in patients who had received no prior systemic therapy for metastatic soft tissue sarcoma. Patients and Methods Patients were randomly assigned 1:1 to receive doxorubicin 75 mg/m2 intravenously day 1 plus palifosfamide 150 mg/m2/d intravenously days 1 to 3 or doxorubicin plus placebo once every 21 days for up to six cycles. The primary end point was progression-free survival (PFS) by independent radiologic review. Results In all, 447 patients were randomly assigned to receive doxorubicin plus palifosfamide (n = 226) or doxorubicin plus placebo (n = 221). Median PFS was 6.0 months for doxorubicin plus palifosfamide and 5.2 months for doxorubicin plus placebo (hazard ratio, 0.86; 95% CI, 0.68 to 1.08; P = .19). Median overall survival was 15.9 months for doxorubicin plus palifosfamide and 16.9 months for doxorubicin plus placebo (hazard ratio, 1.05; 95% CI, 0.79 to 1.39; P = .74). There was a higher incidence of grade 3 to 4 adverse events in the doxorubicin plus palifosfamide arm (63.6% v 50.9%) including a higher rate of febrile neutropenia (21.4% v 12.6%). Conclusion No significant difference in PFS was observed in patients receiving doxorubicin plus palifosfamide compared with those receiving doxorubicin plus placebo. The observed median PFS and overall survival in this large, international study can serve as a benchmark for future studies of doxorubicin in metastatic soft tissue sarcoma.
P2-282: Gemcitabine and vinorelbine combination as second-line therapy in previously taxane and platinum-treated non-small cell lung cancer
Authors: Chi Hoon Maeng, Jae Jin Lee, Sun Kyung Baek, Seong Ha Cheon, Wan Kyu Eo, Si-Young Kim, Hwi Joong Yoon, Kyung Sam Cho
Journal: Journal of Thoracic Oncology (2007)
A7-01: The Danish randomized lung cancer CT screening trial. Results at baseline
Authors: Jesper H. Pedersen, Asger Dirksen, Hanne Hansen, Karen S. Bach, Phillip Tonnesen, John Brodersen, Hanne Thorsen, Birgit G. Skov, Jann Mortensen, Martin Dossing
Journal: Journal of Thoracic Oncology (2007)
Investigation of<i>Escherichia coli</i>Harboring the<i>mcr-1</i>Resistance Gene — Connecticut, 2016
Authors: Amber M. Vasquez, Noelisa Montero, Mark Laughlin, Ehren Dancy, Russell Melmed, Lynn Sosa, Louise Francois Watkins, Jason P. Folster, Nancy Strockbine, Heather Moulton-Meissner, Uzma Ansari, Matthew L. Cartter, Maroya Spalding Walters
Journal: MMWR Morbidity and Mortality Weekly Report (2016)

The mcr-1 gene confers resistance to the polymyxins, including the antibiotic colistin, a medication of last resort for multidrug-resistant infections. The mcr-1 gene was first reported in 2015 in food, animal, and patient isolates from China (1) and is notable for being the first plasmid-mediated colistin resistance mechanism to be identified. Plasmids can be transferred between bacteria, potentially spreading the resistance gene to other bacterial species. Since its discovery, the mcr-1 gene has been reported from Africa, Asia, Europe, South America, and North America (2,3), including the United States, where it has been identified in Escherichia coli isolated from three patients and from two intestinal samples from pigs (2,4-6). In July 2016, the Pathogen Detection System at the National Center for Biotechnology Information (Bethesda, Maryland) identified mcr-1 in the whole genome sequence of an E. coli isolate from a Connecticut patient (7); this is the fourth isolate from a U.S. patient to contain the mcr-1 gene.
Identification of Oncogenic Pathways of T-Acute Lymphoblastic Leukemia (T-ALL) through Gene Expression Profiling of Mouse Tumor Models.
Authors: Maria Luisa Sulis, Teresa Palomero, Pedro J. Real, Kelly C. Barnes, Peter Aplan, Neal Copeland, Dave Utpal, Fotini Gounari, Gerald Grosveld, Dietmar J. Kappes, Barbara Kee, Michelle Kelliher, Jack Lenz, Christine Richardson, Adolfo Ferrando
Journal: Blood (2006)
Prospective teritary centre study of combined modality treatment for malignant pleural mesothelioma (MPM): analysis of first 50 patients
Authors: Philippe Nafteux, Kristiaan Nackaerts, Yolande Lievens, Johnny Moons, Bianca Van Straelen, Johan Vansteenkiste, Marc Decramer, Walter Van den Bogaert
Journal: Journal of Thoracic Oncology (2009)
Building Better Bones with Biologics — A New Approach to Osteoporosis?
Authors: Clifford J. Rosen, Julie R. Ingelfinger
Journal: New England Journal of Medicine (2016)

There is currently a major crisis in osteoporosis therapy.1 Despite effective treatments to prevent fractures, too few patients receive therapy. Furthermore, those who do get treated often stop taking medication prematurely. To understand this paradox and the potential importance of the article by Cosman et al. now published in the Journal,2 a brief historical perspective is required.Until the development and approval of bisphosphonates, which are antiresorptive agents, in the mid-1990s, few effective therapies existed for osteoporosis.3 Bisphosphonates rapidly became the standard of care for osteoporosis and remained so for 15 years. During that time, a relatively small but clinically . . .
O-010 An international phase III randomized, non-inferiority trial comparing 3 vs 6 months of oxaliplatin-based adjuvant chemotherapy for colon cancer: compliance and safety of the phase III Japanese ACHIEVE trial
Authors: T. Eto, M. Kotaka, D. Manaka, J. Hasegawa, A. Takagane, M. Nakamura, T. Kato, Y. Munemoto, F. Nakamura, H. Bando, H. Taniguchi, M. Gamoh, M. Shiozawa, T. Yamanaka, T. Mizushima, J. Sakamoto, S. Saji, M. Mori, A. Ohtsu, T. Yoshino
Journal: Annals of Oncology (2016)
General practitioners' judgment of chronic heart failure in the oldest old. Insights from the BELFRAIL study
Authors: Miek Smeets, Jean-Marie Degryse, Bert Aertgeerts, Stefan Janssens, Wim Adriaensen, Cathy Matheï, Gijs Van Pottelbergh, P Wallemacq, J. L Van Overschelde, Bert Vaes
Journal: European Journal of Heart Failure (2015)
Clopidogrel Versus Ticagrelor for Antiplatelet Maintenance in Diabetic Patients Treated With Percutaneous Coronary Intervention
Authors: Fabio Mangiacapra, Elena Panaioli, Iginio Colaiori, Elisabetta Ricottini, Angelo Lauria Pantano, Paolo Pozzilli, Emanuele Barbato, Germano Di Sciascio
Journal: Circulation (2016)
Vadadustat, a novel oral HIF stabilizer, provides effective anemia treatment in nondialysis-dependent chronic kidney disease
Authors: Pablo E. Pergola, Bruce S. Spinowitz, Charlotte S. Hartman, Bradley J. Maroni, Volker H. Haase
Journal: Kidney International (2016)

Current treatment of anemia in chronic kidney disease (CKD) with erythropoiesis-stimulating agents can lead to substantial hemoglobin oscillations above target range and high levels of circulating erythropoietin. Vadadustat (AKB-6548), a novel, titratable, oral hypoxia-inducible factor prolyl hydroxylase inhibitor induces endogenous erythropoietin synthesis and enhances iron mobilization. In this 20-week, double-blind, randomized, placebo-controlled, phase 2b study, we evaluated the efficacy and safety of once-daily vadadustat in patients with stages 3a to 5 non-dialysis-dependent CKD. The primary endpoint was the percentage of patients who, during the last 2 weeks of treatment, achieved or maintained either a mean hemoglobin level of 11.0 g/dl or more or a mean increase in hemoglobin of 1.2 g/dl or more over the predose average. Significantly, the primary endpoint was met in 54.9% of patients on vadadustat and 10.3% of patients on placebo. Significant increases in both reticulocytes and total iron-binding capacity and significant decreases in both serum hepcidin and ferritin levels were observed in patients on vadadustat compared with placebo. The overall incidence of adverse events was comparable between the 2 groups. Serious adverse events occurred in 23.9% and 15.3% of the vadadustat- and placebo-treated patients, respectively. Three deaths occurred in the vadadustat arm. Thus, this phase 2b study demonstrated that vadadustat raised and maintained hemoglobin levels in a predictable and controlled manner while enhancing iron mobilization in patients with nondialysis-dependent CKD.
Urticaria Multiforme
Authors: Simon Kotlyar
Journal: New England Journal of Medicine (2016)

A 3-year-old girl presented to the ED on day 1 of a mild pruritic urticarial rash. The parents described a viral respiratory illness that had occurred a week earlier. Fever developed on day 2, along with a generalized polycyclic annular rash with wheals and ecchymotic centers.
A Controlled Trial of Interferon Gamma to Prevent Infection in Chronic Granulomatous Disease
Journal: New England Journal of Medicine (1991)

Chronic granulomatous disease is an uncommon inherited disorder of phagocytes in which defective production of the reactive intermediates of oxygen predisposes patients to recurrent and severe pyogenic infections. Evidence from in vitro and in vivo studies indicates that interferon gamma can partially correct the metabolic defect in phagocytes. We assessed the efficacy of interferon gamma in decreasing the frequency of serious infections in patients with this disease.
P2-166: Full dose chemoradiation followed by surgical resection in locally advanced NSCLC
Authors: Hale B. Caglar, Steven J. Mentzer, Jeanne M. Lukanich, Pasi A. Janne, Paul J. Marcoux, Christopher Lathan, Michael S. Rabin, Yolanda L. Colson, Aaron M. Allen
Journal: Journal of Thoracic Oncology (2007)
P3-188: Optimization of lung IMRT Treatment plans using a beam direction and virtual organ delineation
Authors: Suk Lee, Kwang Hwan Cho, Hun Joo Shin, Sang Hoon Lee, Hyundo Huh, Samjoo Cho, Sangwook Lim, Jisun Jang, Dongho Shin, Young Je Park, Nam Kwon Lee, Dae Sik Yang, Chul Yong Kim
Journal: Journal of Thoracic Oncology (2007)