tbuckley/cabot-search huggingface dataset:
Cryobiopsy to increase the detection rate of EGRF-mutations in non-small cell lung cancer.
Authors: Michael Boeckeler, Lothar Kanz, Maik Haentschel, Falko Fend, Hans Bosmuller, Volker Steger, Marius Horger, Ahmed Ehab, Juergen Hetzel
Journal: Journal of Clinical Oncology (2016)

e20613 Background: Activating mutations in the epidermal growth factor receptor (EGFR) gene are pharmacological targets for EGFR tyrosine kinase inhibitors (TKI) in patients with advanced non-small-cell lung cancer (NSCLC) and targeted TKI therapy improves survival in comparison to conventional chemotherapy. This retrospective single center study evaluates the detection rate of mutated EGFR obtained by bronchoscopic cryobiopsy, in comparison to standard sampling techniques. Methods: A total of 420 specimens (03/2008-07/2014) with pathologically confirmed NSCLC and EGFR mutation status tested by Sanger sequencing (Exon 18-21) were studied. Samples obtained by bronchoscopic cryobiopsy were compared with those obtained by other biopsy techniques such as bronchoscopic forceps biopsies, fine needle aspiration, imaging guided transthoracic core needle biopsies and surgical procedures. Results: The cryobiopsy group and the non-cryobiopsy group did not differ regarding smoking history, age and gender. Bronchoscopic cryobiopsy detected activating EGFR mutations in 28 of 126 patients (22.2%) while non cryobiopsy techniques detected mutations in 45 of 294 patients (14.3%) respectively (p = 0.046). 108 cryobiopsies were performed in the central airways, 18 were done in the peripheral airways. There was a non significant higher EGFR mutation rate in bronchoscopic biopsies harvested in the lung periphery compared to the central airways (27% vs. 16,8%). Conclusions: Bronchoscopic cryobiopsy increased the detection rate of activating EGFR mutations in NSCLC compared to other tissue sampling techniques by far. This difference cannot only be explained by an imbalance of biopsy localization. Samples obtained by cryobiopsy might provide better material to detect mutations of EGRF. The higher rate of EGFR mutations in the cryobiopsy group suggests, that there might be false negative results with current sampling techniques and therefore may explain response to TKI of EGFR wild type declared NSCLC patients. As the detection of EGFR mutations is crucial for treatment strategy, cryobiopsy may improve the outcome of a substantial number of patients. A prospective trial comparing cryobiopsy versus forceps biopsy will be initiated
Bevacizumab plus XELOX as first-line therapy for patients with metastatic colorectal cancer
Authors: E. Gaspar, A. Juarez Marroqui, J. Vicent, C. Llorca, D. Orts, A. Galan, E. Barrajon, J. Cervera Grau, V. Giner, S. Macia
Journal: Journal of Clinical Oncology (2008)

15114 Background: Bevacizumab (BEV) is a monoclonal antibody that inhibits tumour angiogenesis by targeting VEGF. In a phase III trial, BEV significantly improved overall (OS) and progression-free survival (PFS) when combined with first-line irinotecan plus bolus 5-fluorouracil (5-FU)/leucovorin (LV) (IFL) in patients with metastatic colorectal cancer (mCRC). Methods: Patients had to have: mCRC; no surgery within 28 days; no prior CT for metastatic disease; ECOG PS 0/1, adequate organ function. CT consisted in Xelox (oxaliplatine 130 mg/m2 plus capecitabine 1000 mg/m2 bid 14 days) plus BEV 7,5 mg/kg was given on day 1 with every 3 weeks. Tumour assessments were performed every 3 cycles. The primary objective was PFS and overall response; secondary objectives included safety, and OS. Results: By July, 2006, 35 pts had been enrolled. Male 71%; median age 64 years; PS 0–1 (88,6%). The most common site of metastases was liver (100%). Among the 35p. Related grade 3–4 AEs were reported in 10 (28,6%) pts. GI perforation 3%, diarrhea 8,6%, hypertension 3%; neuropathy 6%. Overal response was observed in 63% pts (CR 3%; PR 60%). Conclusions: The scarce toxicity, the efffectiveness and the non requirement of central venous access, make it an interesting alternative to the first line treatment of colorectal cancer. No significant financial relationships to disclose.
S115 Efficacy of Pseudomonas aeruginosa eradication regimens in non-CF bronchiectasis: Abstract S115 Table 1
Authors: E Vallieres, K Tumelty, MM Tunney, R Hannah, O Hewitt, JS Elborn, DG Downey
Journal: Thorax (2015)

<h3>Introduction and objectives</h3> BTS guidelines recommend to try and eradicate <i>Pseudomonas aeruginosa</i> when first isolated from patients with non-CF bronchiectasis. The aims of this study were to 1) define the different eradication regimens used in our respiratory centre and 2) evaluate their efficacy. <h3>Methods</h3> The medical notes of adult non-CF bronchiectasis patients who underwent eradication trial for <i>P. aeruginosa, </i>between 2007 and 2014, were retrospectively reviewed. Eradication was considered successful if all (and at least 3) respiratory samples collected during the 6-month period following initiation of eradication were free of <i>P. aeruginosa</i>. <h3>Results</h3> During the study period, 67 patients (58% male, average age 63.0 yrs) had at least one eradication trial. The majority of regimens used combined nebulised colomycin with either oral ciprofloxacin or intravenous antipseudomonal antibiotics as first line therapy, (Table 1, n = 57; 85%). Overall, first eradication attempts were successful in 52% of cases (35/67). Regimens including nebulised colomycin were more effective (n = 23/38; 60%) than those without it (20%; 2/10) (Fisher`s exact test, <i>p = 0</i>.04). Longer courses of ciprofloxacin (&gt;3 weeks) did not improve outcome in comparison with shorter (≤3 weeks) courses (<i>p</i> = NS). Furthermore, intravenous antibiotics were not superior to oral ciprofloxacin (<i>p</i> = NS). Amongst the 32 patients who failed to eradicate <i>P. aeruginosa</i> in the first instance, 20 underwent a second attempt. In comparison with first trials, overall success rate of second trials decreased to 35% (n = 7/20). However, this difference did not reach statistical significance (Fisher`s exact test, <i>p = 0</i>.3). Nineteen patients, who initially successfully cleared <i>P. aeruginosa</i>, required a 2<sup>nd</sup> eradication trial later during the study period. For those patients, the eradication success was 53%, comparable to the first one. <h3>Conclusions</h3> Eradication regimens combining systemic and nebulised antibiotics appear more effective than systemic antibiotics alone to achieve <i>P. aeruginosa</i> eradication in non-CF bronchiectasis patients.
Clinical effectiveness and acceptability of structured group psychoeducation versus optimised unstructured peer support for patients with remitted bipolar disorder (PARADES): a pragmatic, multicentre, observer-blind, randomised controlled superiority trial
Authors: Richard Morriss, Fiona Lobban, Lisa Riste, Linda Davies, Fiona Holland, Rita Long, Georgia Lykomitrou, Sarah Peters, Christopher Roberts, Heather Robinson, Steven Jones
Journal: The Lancet Psychiatry (2016)
MicroRNA-221/-222 amends protective mechanisms in CVB3-induced murine myocarditis
Authors: Ward Heggermont, M Corsten, Anna-Pia Papageorgiou, Hendrik Jan Thibaut, W Verhesen, Paolo Carai, R Van Leeuwen, Johan Neyts, B Schroen, Stephane Heymans
Journal: European Journal of Heart Failure (2014)
Metabolic Effects of Intermittent Fasting
Authors: Ruth E. Patterson, Dorothy D. Sears
Journal: Annual Review of Nutrition (2017)

The objective of this review is to provide an overview of intermittent fasting regimens, summarize the evidence on the health benefits of intermittent fasting, and discuss physiological mechanisms by which intermittent fasting might lead to improved health outcomes. A MEDLINE search was performed using PubMed and the terms "intermittent fasting," "fasting," "time-restricted feeding," and "food timing." Modified fasting regimens appear to promote weight loss and may improve metabolic health. Several lines of evidence also support the hypothesis that eating patterns that reduce or eliminate nighttime eating and prolong nightly fasting intervals may result in sustained improvements in human health. Intermittent fasting regimens are hypothesized to influence metabolic regulation via effects on (a) circadian biology, (b) the gut microbiome, and (c) modifiable lifestyle behaviors, such as sleep. If proven to be efficacious, these eating regimens offer promising nonpharmacological approaches to improving health at the population level, with multiple public health benefits.
Dose-Dense Induction (Sequential-HAM) in Primary Acute Myeloid Leukemia - A Pilot Study of the AML-CG.
Authors: Jan Braess, Peter Staib, Wolf D. Ludwig, Bernhard J. Wormann, Andreas Reichle, Wolfgang Berdel, Thomas Buchner, Andreas Gruneisen, Christoph Schmid, Christian Schmid, Wolfgang Kern, Karsten Spiekermann, Michael Fiegl, Michaela Feuring-Buske, Stefan Bohlander, Achim Heinicke, Christ Sauerland, Michael Unterhalt, Wolfgang Hiddemann
Journal: Blood (2006)
Analysis of molecular mechanisms of response and resistance to vemurafenib (vem) in <i>BRAF<sup>V600E </sup></i>melanoma.
Authors: Jeffrey Alan Sosman, Anna C. Pavlick, Lynn Mara Schuchter, Karl D Lewis, Grant A. McArthur, Charles Lance Cowey, Stergios J Moschos, Keith T. Flaherty, Kevin B. Kim, Jeffrey Weber, Peter Hersey, Georgina V. Long, Donald P. Lawrence, Mark Kockx, Olivia Spleiss, Astrid Koehler, Gideon Bollag, Andrew K. Joe, Kerstin Trunzer, Antoni Ribas
Journal: Journal of Clinical Oncology (2012)

8503^ Background: Vem induces frequent clinical responses (RR &gt;50%) and improved survival in patients (pts) with BRAF-mutated metastatic melanoma. Multiple mechanisms of escape from vem have been proposed. We performed a centralized analysis of pretreatment, cycle 1, day 15 (D15), and progression (DP) tumor samples collected during the phase II BRIM-2 trial (Sosman et al, NEJM 2012). Methods: Of 132 pts enrolled, archival tumor samples, biopsies taken at baseline (BL), D15, and DP were obtained from 84, 38, 26, and 22 pts, respectively, and analyzed by immunohistochemistry (IHC) for signaling molecules in the MAPK, PI3K/AKT, and cell cycle pathways. Genetic analyses of signaling genes were performed using Sequenom MASSarray and direct DNA sequencing. Results: High levels of ERK phosphorylation were seen at BL indicating constitutive MAPK signaling due to the BRAF mutation. In 19/22 paired samples, pERK levels were reduced following vem (BL vs D15). Mean absolute pERK reduction in pts with clinical response (RECIST criteria) to vem (n=14) was significantly greater than in non-responders (n=8; p=0.013). Baseline cytoplasmic PTEN H-score was higher in responders vs non-responders (H-score=88 vs 68; p=0.042). At progression, upregulation of pERK (H-score=181) was frequently, but not uniformly found vs D15 tumors (H-score=48.5). At progression, increases in Cyclin D1 and Ki67 were seen, without obvious changes in PTEN or pAKT. NRAS mutations occurred in 3/13 DP; 2 had paired BL samples without NRAS mutations. Only 1/82 pts had a concomitant NRAS and BRAF mutation at BL, and did not respond to vem. MAP2K1 (MEK1) codon 124 mutations occurred in 7/92 BL and 1/20 DP samples. 2 pts with BL MEK1 mutations had partial responses. Conclusions: MAPK signaling was effectively inhibited by vem early in treatment, and in the subset of patients with matched tumor samples the degree of pathway inhibition correlated with clinical response. MAPK signaling is upregulated in many lesions at progression. NRAS mutations appear to be a mechanism of acquired resistance in a few tumors (3/13), while the role of MEK1 mutations in resistance is less clear.
Mucus‐Penetrating Nanosuspensions for Enhanced Delivery of Poorly Soluble Drugs to Mucosal Surfaces
Authors: Tao Yu, Jane Chisholm, Woo Jin Choi, Abraham Anonuevo, Sarah Pulicare, Weixi Zhong, Minmin Chen, Colleen Fridley, Samuel K. Lai, Laura M. Ensign, Jung Soo Suk, Justin Hanes
Journal: Advanced Healthcare Materials (2016)

Mucus-penetrating nanosuspensions, consisting of pure hydrophobic therapeutics with dense muco-inert coatings that enable particles to effectively bypass the mucus barrier, demonstrate superior drug distribution and absorption at mucosal surfaces. With significantly increased drug load compared to polymeric systems and established clinical translation of nanosuspensions-based products, mucus-penetrating nanosuspensions are a promising vehicle for improving mucosal delivery of poorly soluble drugs.
Abstract 9150: Re-Elevation of Troponin Following Percutaneous Coronary Intervention Significantly Predicts 1-Year Mortality in Patients with High-risk Non-ST-Segment Elevation Acute Coronary Syndromes
Authors: Pierluigi Tricoci, Sergio Leonardi, Jennifer A White, Brian Tinga, Robert P Giugliano, Harvey D White, Paul W Armstrong, Neal S Kleiman, Vitaly A Sulimov, Jean-François Tanguay, Basil S Lewis, Stefan K James, C. M Gibson, Eugene Braunwald, Frans Van de Werf, Robert M Califf, Kenneth W Mahaffey, L. K Newby
Journal: Circulation (2011)

Background: The prognostic value of cardiac troponin (cTn) elevation post PCI is controversial. Moreover, in high-risk NSTE ACS patients presenting with elevated necrosis markers, the ability to use cTn to detect post-PCI MI is especially challenging: primarily this relates to discriminating PCI-related elevation from natural evolution of presenting MI. We addressed this issue by reviewing each cTn trend during the index ACS admission in all patients undergoing PCI randomized in the EARLY ACS (n=5552) and SYNERGY (n=4647) trials. Methods: Time and cTn value (indexed by ULN) data pairs were plotted into graphics for each of 10,199 pts and independently reviewed by 2 physicians to detect post-PCI cTn (re)elevation (example in figure). Post-PCI cTn peak was identified for each plot, and the relationship between peak cTn post PCI and 1-year mortality was evaluated using Cox proportional hazard modeling, correcting for the 15 clinical variables of the EARLY ACS 1-year mortality model (including baseline cTn). Results: Patients were classified into 3 groups: (i) (re)elevation post PCI not evaluable because cTn values rising through the time of PCI (group 1; N=4427 [43%]; excluded from further analyses); (ii) cTn values stable/falling with post-PCI (re)elevation detected (group 2; N=4276 [42%]); (iii) cTn values stable/falling but without post-PCI (re)elevation (group 3; n=1496 [15%]). In the multivariable model including patients in groups 2 and 3, peak cTn post PCI was significantly associated with a 7% increase in hazard of death per each 10xULN increase (adj. HR 1.07; 95% CI 1.03-1.11; p=0.0008). Conclusion: We describe a methodology that allows clear differentiation of post-PCI cTn (re)elevation from presenting MI in over half of high-risk NSTE ACS patients undergoing PCI. This approach identified a highly significant relationship between post-PCI cTn and 1-year mortality and has relevance for the incorporation of cTn for definition of post-PCI MI.
Effect of weekly administration of bevacizumab, eribulin, and oxalilplatin in patients with heavily pretreated serous ovarian carcinoma.
Authors: Yuji Ikeda, Masashi Takano, Naoki Sasaki, Tsunekazu Kita, Yoshihiro Kikuchi, Kazuya Kudoh
Journal: Journal of Clinical Oncology (2013)

e16506 Background: Eribulin, inhibiting a protein component of tubulin, extend the lifespan of patients with late-stage breast cancer who are not benefiting paclitaxel. Bevacizumab (B) is known to enhance chemotherapeutic efficacy of platinum agents. We evaluated the effect of weekly administration of B with eribulin and oxaliplatin (EriOX) in recurrent or refractory serous ovarian carcinoma patients (ROC) pretreated with paclitaxel and carboplatin. Methods: Thirteen patients with ROC had treated with weekly-B and EriOX consisting of B (2mg/kg), eribulin (1mg/m2) and oxaliplatin (30mg/m2). The response and adverse effects (AE) were evaluated using the response evaluation criteria in solid tumors (RECIST), CA125 Gynecologic Cancer Intergroup (GCIG) criteria, and common terminology criteria for adverse events (CTCAE) version 4.0. Results: One patient is still under treatment of two cycles. We evaluated 12 patients at least two or more cycles of weekly B and EriOX. Ten patients (83%) were primarily stage 3 or 4. Ten patients (83%) had received three or more regimens of chemotherapy. All patients were pretreated with paclitaxel and carboplatin and 9 patients (75%) had been pretreated with platinum containing regimen within 6 months. According to the RECIST evaluation, 2 patients (17%) had a complete response (CR), 1 patient (8%) had a partial remission (PR) and 3 patients (25%) had a stable disease (SD). The response rate (CR+PR) and clinical benefit rate (CR+PR+SD) were 25% and 50%, respectively. Median progression-free survival was 3 months (range: 1-5 months). Hematological AEs with grade 3/4 were observed in 2 patients (17%). Hypo albuminemia and edema with grade 3 were in 1 patient (8%), respectively. However, all AE were manageable and torelable. Conclusions: Weekly B and EriOX administration had significant activity with mild AE in patients with paclitaxel and platinum resistant ROC. These results warrant further prospective study.
BCL-6 gene expression by immunohistochemistry in normal lymphoid tissue and B-cell non-Hodgkin' s lymphomas with and without BCL-6 rearrangement
Authors: S Pittaluga, Iwona Wlodarska, Michel Stul, Christina Mecucci, Jean-Jacques Cassiman, Herman Van den Berghe, Gregor Verhoef, Christiane Peeters
Journal: Blood (1994)
A Phase 2 Study of 90Y-Ibritumomab Tiuxetan (90Y-Zevalin®) in Relapsed/Refractory Non-Hodgkin’s Lymphoma: Preliminary Report of the Argentinean Cooperative Group.
Authors: Roberto E. Cacchione, Jorge Milone, Javier Bordone, Juan Dupont, Gustavo Milone, Dardo Riveros, Pedro Negri, María Ardaiz, Leandro Riera, Maria Cecilia Foncuberta, Fernando Bezares
Journal: Blood (2006)
Nitric Oxide Synthase 3 Predisposes to Adverse Left Ventricular Remodeling in Insulin Resistance
Authors: Helene Thibault, Michael J Raher, Emmanuel Buys, Sharon Cawley, Genevieve Derumeaux, Stefan Janssens, Michael H Picard, Kenneth D Bloch, Marielle Scherrer-Crosbie
Journal: Circulation (2008)
Overall survival (OS) analysis from PRIME: Randomized phase III study of panitumumab (pmab) with FOLFOX4 for first-line metastatic colorectal cancer (mCRC).
Authors: Jean-Yves Douillard, Salvatore Siena, Josep Tabernero, Ronald L. Burkes, Mario Edmundo Barugel, Yves Humblet, Gyorgy Bodoky, David Cunningham, Jacek Jassem, Fernando Rivera, Ilona Kocáková, Paul Ruff, Martin Smakal, Jean-Luc Canon, Mark Rother, Kelly S. Oliner, Ying Tian, Roger Sidhu
Journal: Journal of Clinical Oncology (2013)

3620 Background: The primary and final analyses of PRIME demonstrated that pmab + FOLFOX4 significantly improved progression-free survival (PFS) vs FOLFOX4 alone for first-line treatment of patients (pts) with wild-type (WT) KRAS exon 2 mCRC. Methods: Pts were randomized 1:1 to pmab 6.0 mg/kg every 2 weeks + FOLFOX4 or FOLFOX4 alone and had no prior chemotherapy for mCRC, ECOG performance status ≤ 2, and tumor tissue for biomarker testing. The primary endpoint was PFS by central assessment. Secondary endpoints included OS, objective response rate, and safety. KRAS exon 2 tumor status was determined by a blinded central lab prior to the primary analysis. This exploratory analysis of updated survival (&gt;80% OS events) estimated the treatment effect of pmab + FOLFOX4 compared with FOLFOX4 alone on OS by KRAS exon 2 status. Previous analyses in pts with WT KRAS exon 2 tumor status reported OS with an event rate of 54% of pts in the primary analysis and 68% of pts in the final analysis. Results: 1183 pts were randomized and received treatment: 593 pts in the pmab + FOLFOX4 arm and 590 pts in the FOLFOX4 alone arm. The KRAS exon 2 ascertainment rate was 93%, consistent with the primary analysis. 535/656 pts (82%) with WT KRAS exon 2 mCRC had an OS event at the time of this analysis. Results are shown (Table). Conclusions: In this updated analysis, an improvement in OS was observed in pts with WT KRAS exon 2 mCRC treated with pmab + FOLFOX4 vs FOLFOX4 alone (p = 0.03). Median OS was reduced in pts with mutant (MT) KRAS mCRC (p = 0.16) and is consistent with previous analyses. Updated efficacy and safety results will be presented. KRAS testing is critical to select appropriate pts with mCRC for treatment with pmab. Clinical trial information: NCT00364013. [Table: see text]
P0313 : Correlation between VEGF and VEGF-R polymorphisms, toxicity and clinical outcome in HCC patients receiving sorafenib
Authors: L. Faloppi, M. Bianconi, G. Svegliati Baroni, A. Casadei Gardini, N. Silvestris, G. Masi, P. Ulivi, C. Vivaldi, R. Giampieri, M. Del Prete, A. Benedetti, M. Scartozzi, S. Cascinu
Journal: Journal of Hepatology (2015)
Isolated hearts of Delta KPQ SCN5A mutated (Long-QT3) mice exhibit bradycardia, early afterdepolarizations, and torsade de pointes arrhythmias which are suppressed by pacing or mexiletine
Authors: L Fabritz, P Kirchhof, Franz, Dieter Nuyens, Tom Rossenbacker, B Riemann, W Haverkamp, M Schaefers, W Schmitz, G Breithardt, E Carmellet, Peter Carmeliet
Journal: Circulation (2002)
Genetic Associations with Therapy Response in the HOVON-65/GMMG-HD4 Trial in Patients with Multiple Myeloma.
Authors: Sophie L Corthals, Hartmut Goldschmidt, David C Johnson, Henk Lokhorst, Yvonne de Knegt, Sonja Zweegman, Bronno van der Holt, Dirk Hose, Marie Jose Kersten, Edo Vellenga, Brian G M Durie, Gareth J Morgan, Pieter Sonneveld
Journal: Blood (2009)
G Protein–Coupled Receptor Kinase 2
Authors: Meryl C. Woodall, Michele Ciccarelli, Benjamin P. Woodall, Walter J. Koch
Journal: Circulation Research (2014)

Heart failure (HF) causes a tremendous burden on the worldwide healthcare system, affecting &gt;23 million people. There are many cardiovascular disorders that contribute to the development of HF and multiple risk factors that accelerate its occurrence, but regardless of its underlying cause, HF is characterized by a marked decrease in myocardial contractility and loss of pump function. One biomarker molecule consistently shown to be upregulated in human HF and several animal models is G protein–coupled receptor kinase-2 (GRK2), a kinase originally discovered to be involved in G protein–coupled receptor desensitization, especially β-adrenergic receptors. Higher levels of GRK2 can impair β-adrenergic receptor–mediated inotropic reserve and its inhibition, or molecular reduction has shown to improve pump function in several animal models including a preclinical pig model of HF. Recently, nonclassical roles for GRK2 in cardiovascular disease have been described, including negative regulation of insulin signaling, a role in myocyte cell survival and apoptotic signaling, and it has been shown to be localized in/on mitochondria. These new roles of GRK2 suggest that GRK2 may be a nodal link in the myocyte, influencing both cardiac contractile function and cell metabolism and survival and contributing to HF independent of its canonical role in G protein–coupled receptor desensitization. In this review, classical and nonclassical roles for GRK2 will be discussed, focusing on recently discovered roles for GRK2 in cardiomyocyte metabolism and the effects that these roles may have on myocardial contractile function and HF development.
Tumor-stroma cross-talk in the study of the osteoclastogenic potential of a metastatic breast cancer cell line: a coculture system
Authors: F. La Manna, C. Liverani, A. De Vita, L. Mercatali, C. Spadazzi, Y. Kang, A. Bongiovanni, N. Riva, M. Ricci, S. Calpona, D. Amadori, T. Ibrahim
Journal: Annals of Oncology (2015)
Inv(2)(p23q35) in anaplastic large-cell lymphoma induces constitutive ALK tyrosine kinase activation by fusion to ATIC, an enzyme involved in purine nucleotide biosynthesis
Authors: Z Ma, Jan Cools, Peter Marynen, X Cui, R Siebert, S Gesk, B Schlegelberger, Benjamin Peeters, Christiane Peeters, Iwona Wlodarska, SW Morris
Journal: Blood (1999)