tbuckley/cabot-search huggingface dataset:
Abstract 15095: Beneficial Effects of Riociguat on Hemodynamic Responses to Exercise in CTEPH Patients After Balloon Pulmonary Angioplasty
Authors: Tatsuo Aoki, Koichiro Sugimura, Shunsuke Tatebe, Masanobu Miura, Saori Yamamoto, Haruka Satoh, Nobuhiro Kikuchi, Ryo Konno, Yosuke Terui, Miku Sakota, Kotaro Nochioka, Kimio Satoh, Hiroaki Shimokawa
Journal: Circulation (2018)

Background: Balloon pulmonary angioplasty (BPA) improves resting hemodynamics in patients with chronic thromboembolic pulmonary hypertension (CTEPH) and consequently enables us to discontinue pulmo...
CORTICOSTEROID TAPERING AND DISCONTINUATION IN A PHASE 2 STUDY OF RILONACEPT IN RECURRENT PERICARDITIS
Authors: Allan Klein, S. Allen Luis, Martin M. LeWinter, David Lin, Paul Cremer, Saifullah Nasir, Antonio Abbate, Andrew Ertel, Fang Fang, Anna Beutler, John Paolini
Journal: Journal of the American College of Cardiology (2020)
IMPACT OF BIFURCATION ANGLE, GUIDEWIRE RE-CROSSING POSITION AND STENT LINK LOCATION FOR OPTIMAL KISSING BALLOON INFLATION: NINE-MONTH FOLLOW-UP OPTICAL COHERENCE TOMOGRAPHY RESULTS IN JAPANESE 3D-OCT BIFURCATION REGISTRY
Authors: Masahiro Yamawaki, Takayuki Okamura, Ryoji Nagoshi, Tatsuhiro Fujimura, Yoshinobu Murasato, Shiro Ono, Takeshi Serikawa, Yutaka Hikichi, Hiroaki Norita, Fumiaki Nakao, Tomohiro Sakamoto, Toshiro Shinke, Junya Shite
Journal: Journal of the American College of Cardiology (2020)
Distinct PIK3CA mutation profiles in estrogen receptor (ER) negative breast cancer (BC) subsets
Authors: A. S. Doane, M. Danso, P. Lal, M. Donaton, J. Wheler, M. Moynahan, L. Zhang, C. Hudis, W. Gerald
Journal: Journal of Clinical Oncology (2006)

540 Background: ER negative, progesterone receptor (PR) negative BC is clinically heterogeneous and underlying biology may be complex. We have identified two primary subtypes of ER(-)/PR(-) BC based on genome-wide molecular analysis (Doane et al., 2005, Oncogene, In Press), however the biological mechanisms underlying these molecular differences are not known. Methods: We performed genome-wide expression analysis of 99 primary BC samples and 13 BC cell lines. Total RNA was extracted and hybridized to Affymetrix HG-U133 oligonucleotide microarrays. Unsupervised and supervised analyses were used to investigate gene expression profiles. Predictive models were developed using a supervised k-nearest neighbor technique. Samples were further characterized by immunohistochemistry (IHC) for selected gene products, and HER2 status was determined by IHC and FISH. PIK3CA exons 9 and 20 were sequenced by RT-PCR amplification, direct sequencing, and restriction enzyme digest. Results: Genes differentially expressed between ER(-)/PR(-) subsets (designated class A and B) included SPDEF, ALCAM, AR, and FGFR4 (p&lt;0.0001). Further study revealed a significant association with class A and the PIK3CA A3140G:H1047R activating mutation among ER(-)/PR(-) BC (p=0.012). HER2 status (gene amplification or 3+ IHC) was not significantly associated with this subtype (p=0.33). MDA-MB-453 corresponded to class A according to molecular profile and PIK3CA mutation status. This cell line demonstrated a proliferative response to androgen (A) in an androgen receptor (AR) dependent and ER-independent manner. In addition the A-induced transcriptional program of MDA-MB-453 significantly overlapped the molecular signature of ER(-)/PR(-) class A human BC (p&lt;0.0001). Conclusion: Hormonal signaling through the AR may be significantly different in ER(-)/PR(-) molecular subsets. Enhanced AR signaling may be due to cooperation with growth factor signaling through PI3K. The potential molecular crosstalk between activated PI3K and the androgen signaling pathway provides therapeutic opportunities and deserves further study. No significant financial relationships to disclose.
Phase II study evaluating trimodal therapy with cetuximab intensity modulated radiotherapy (IMRT) and gemcitabine for patients with locally advanced pancreatic cancer [ISRCTN56652283]
Authors: R. C. Krempien, M. W. Münter, C. Timke, P. E. Huber, H. Friess, S. Heeger, K. K. Herfarth, A. Abdollahi, G. Hartung, M. W. Buchler, J. Debus
Journal: Journal of Clinical Oncology (2006)

4100 Background: The induction of EGFR targeting with cetuximab in radiation based therapy of solid tumors has yielded promising results. Thus, we initiated a prospective Phase II trial designed to analyze the feasibility and effectivity of trimodal therapy with gemcitabine-based chemoradiation and cetuximab in locally advanced inoperable pancreatic cancer. Methods: In this phase 2 study, pts with locally advanced pancreatic cancer without prior cytotoxic therapy were treated with radiotherapy (RT), gemcitabine weekly (300 mg/m 2 ), and cetuximab weekly (loading dose 400 mg/m 2 day 1, and concomitant with radiation day 8,15,22,29,36 250 mg/m 2 ). RT was delivered by using an integrated IMRT boost concept (54 Gy GTV, 45 Gy CTV) over 5 weeks. RT was followed by gemcitabine (1000 mg/m 2 ) weekly × 3 in 4 weeks. Response evaluation using computed tomography followed at week 12. All amenable patients were intended for surgical treatment between week 12–15. Results: 24 pts were enrolled until now. Preliminary results are presented on 20 pts with the following characteristics: pancreatic adenocarcinoma c2 T4 N1 20/20, median age = 63.5 (range 51–79); M/F = 13/7; ECOG PS 0/1/2 = 2/12/6; median days on treatment: 90 (range 70–100). Treatment-related toxicities were observed in 16 pts. Grade 3 toxicities included diarrhea (n = 4), fatigue (n = 2), nausea (n = 3), neutropenia (n = 6), thrombocytopenia (n = 2), and vomiting (n = 2). 18/20 pts developed some acneiforme rush during therapy. No omittance of cetuximab therapy was necessary. 1 patient died during RT due to tumor bleeding. Median follow-up at present is 6 month, median survival has not been reached. Partial remissions 8/20, stable disease 9/20, progressive disease 3/20. 12/20 patients were amenable for secondary potentially curative resection. 4 patients could be resected, while 3 patients were found to have abdominal metastatic spread. Conclusions: Early data from trimodal therapy in pancreatic adenocarcinoma with chemoradiation (IMRT), gemcitabine, and cetuximab indicate feasibility without increased toxicity profile. The local response appears to be very promising in pancreatic cancer, potentially allowing neoadjuvant treatment. [Table: see text]
Towards an understanding of the physical activity-BDNF-cognition triumvirate: A review of associations and dosage
Authors: Erin I. Walsh, Lisa Smith, Joe Northey, Ben Rattray, Nicolas Cherbuin
Journal: Ageing Research Reviews (2020)

Physical activity has received substantial research attention due to its beneficial impact on cognition in ageing, particularly via the action of brain-derived neurotrophic factor (BDNF). It is well established that physical activity can elevate circulating levels of BDNF, and that BDNF has neurotrophic, neuroprotective and cognitively beneficial properties. Yet, practical implementation of this knowledge is limited by a lack of clarity on context and dose-effect. Against a shifting backdrop of gradually diminishing physical and cognitive capacity in normal ageing, the type, intensity, and duration of physical activity required to elicit elevations in BDNF, and more importantly, the magnitude of BDNF elevation required for detectable neuroprotection remains poorly characterised. The purpose of this review is to provide an overview of the association between physical activity, BDNF, and cognition, with a focus on clarifying the magnitude of these effects in the context of normative ageing. We discuss the implications of the available evidence for the design of physical activity interventions intended to promote healthy cognitive ageing.
TEMPORAL TRENDS IN SEVERITY IN CLINICAL RISK PROFILES AMONG PATIENTS HOSPITALIZED FOR HEART FAILURE
Authors: Carine Hamo, Adam DeVore, Gregg C. Fonarow, Stephen Greene, Muthiah Vaduganathan, Clyde W. Yancy, Paul A. Heidenreich, Di Lu, Roland Matsouaka, Javed Butler
Journal: Journal of the American College of Cardiology (2020)
PERFORMANCE OF A NOVEL GENETIC RISK SCORE TO IDENTIFY RISK OF VENOUS THROMBOEMBOLISM IN PATIENTS WITH CARDIOMETABOLIC DISEASE
Authors: Nicholas Marston, Giorgio Melloni, Yared Gurmu, Christina Lee, Frederick Kamanu, Carolina Roselli, Marc P. Bonaca, Ilaria Cavallari, Robert Giugliano, Benjamin M. Scirica, Deepak Bhatt, Philippe Gabriel Steg, Marc Cohen, Robert Storey, Terje Pedersen, Anthony C. Keech, Itamar Raz, Ofri Mosenzon, Eugene Braunwald, Steven Lubitz, Patrick T. Ellinor, Marc Sabatine, Christian T. Ruff
Journal: Journal of the American College of Cardiology (2020)
THE COMBINATION THERAPY OF ANTI-PD1 ANTIBODY PEMBROLIZUMAB AND ANTI-HER2 ANTIBODY TRASTUZUMAB EXERTS CARDIOTOXIC, PRO-INFLAMMATORY AND PRO-FIBROTIC PROPERTIES IN PRECLINICAL MODELS
Authors: Nicola Maurea, Vincenzo Quagliariello, Antonietta Caronna, Domenica Rea, Antonio Barbieri, Maria Gaia Monti, Rosario Vincenzo Iaffaioli, Michelino De Laurentiis, Paolo Ascierto, Gerardo Botti
Journal: Journal of the American College of Cardiology (2020)
CLINICAL FRAMEWORK FOR THE STAGING OF REVERSE CARDIAC REMODELING WITH MECHANICAL UNLOADING AND CIRCULATORY SUPPORT
Authors: Palak Shah, Mitchell Psotka, Iosif Taleb, Rami Alharethi, Mortada Shams, Omar Wever-Pinzon, Michael Yaoyao Yin, Federica Latta, Josef Stehlik, James Fang, Ramesh Singh, Wei Zhu, Christopher May, Lauren Cooper, Shashank Desai, Craig Selzman, Abdallah Kfoury, Stavros Drakos
Journal: Journal of the American College of Cardiology (2020)
SAFETY OF SAME-DAY DISCHARGE FOR LEFT ATRIAL APPENDAGE OCCLUSION IN PATIENTS WITH ATRIAL FIBRILLATION: A RETROSPECTIVE SINGLE-CENTER STUDY
Authors: Bryan E-Xin Tan, Abdullah Sayied Abdullah, Erfan Alotaki, Dmitry Chuprun, Abrar Shah, Mohan Rao, Jeremiah Peter Depta
Journal: Journal of the American College of Cardiology (2020)
BEZ235 in combination with everolimus for advanced solid malignancies: Preliminary results of a phase Ib dose-escalation study.
Authors: Mohamad Adham Salkeni, Olivier Rixe, Nagla Abdel Karim, Sue Ogara, Monica Feiler, Ganesh Moorthy, Carol A Mercer, Hala Thomas, Pankaj B Desai, Hassana Fathallah, Sara Kozma, George Thomas, John Charles Morris
Journal: Journal of Clinical Oncology (2013)

e13518 Background: The mammalian target of rapamycin (mTOR) is a critical signaling pathway in many tumors including cancers of the breast and colon, glioblastoma multiforme, and hepatocellular carcinoma (HCC). Preclinical studies demonstrated the combination of BEZ235, a competitive dual phosphatidylinositide 3-kinase (PI3K)/mTOR inhibitor, and the mTOR inhibitor, everolimus led to greater regression of a carcinogen-induced HCC than treatment with higher doses of either drug alone. Based on this, we initiated a study of BEZ235 combined with everolimus in patients with advanced solid tumors. Methods: A single institution phase Ib dose-escalation study. Patients with advanced solid malignancies, no available standard of care treatment option, and ECOG performance status 0-2 were eligible. Prior treatment with PI3K inhibitors was not allowed. Sequential cohorts of 3-6 patients were treated. The starting dose was everolimus 2.5 mg and BEZ235 200 mg daily in an oral sachet formulation. Cohort 2 received everolimus 2.5 mg and BEZ235 400 mg daily. Pharmacokinetic and pharmacodynamic studies were performed during the first cycle. The phosphorylation of specific downstream effectors of the mTOR pathway was assessed in peripheral blood mononuclear cells (PBMC). Results: Eleven patients, median age 58 (36-73 years) were treated. Tumors included non-small cell lung cancer, colon cancer, and glioblastoma, hepatocellular carcinoma, pancreatic cancer, esophageal cancer, adenoid cystic carcinoma of the larynx, and appendiceal carcinoma. Four patients were treated on cohort 1. None experienced dose-limiting toxicity. Seven patients were treated on the second dose cohort. One patient withdrew necessitating replacement and another developed grade 3 stomatitis from herpes virus requiring cohort expansion. The most common adverse events were thrombocytopenia, lymphopenia, transaminitis, diarrhea, nausea and fatigue. No tumor responses were noted. PBMC showed a decrease in 4E-BP1S65 phosphorylation on day 28 in 2 of 3 patients in cohort 1. Conclusions: The combination of BEZ235 and everolimus was well tolerated at these doses. The trial remains open to accrual. Clinical trial information: NCT01508104.
Abstract 12385: Resource Utilization in Risk Stratification of Patients Presenting to the Emergency Department With Chest Discomfort
Authors: Sheela Krishnan, Senthil Selvaraj, Ruth Tamrat, Shan Davis, Ashwin Murthy, Dipika Gopal, David McCarthy, Andrew Litwack, Michael Riley, Daniel Kolanksy, Frank Silvestry, Srinath Adusumalli
Journal: Circulation (2018)

Introduction: Chest discomfort is a common clinical challenge in emergency departments nationwide and stress testing is frequently used to risk stratify patients presenting with this complaint. Und...
EFFICACY AND SAFETY OF DABIGATRAN ETEXILATE VERSUS VITAMIN K ANTAGONIST FOR TREATMENT OF ACUTE VENOUS THROMBOEMBOLISM IN ROUTINE CLINICAL PRACTICE: RECOVERY DVT/PE PROSPECTIVE GLOBAL COHORT STUDY
Authors: Samuel Goldhaber, Walter Ageno, Ivan Casella, Kok Han Chee, Sebastian Schellong, Daniel E. Singer, Isabelle Voccia, Wenbo Tang, Sam Schulman
Journal: Journal of the American College of Cardiology (2020)
MOR202, a novel anti-CD38 monoclonal antibody, in patients with relapsed or refractory multiple myeloma: a first-in-human, multicentre, phase 1–2a trial
Authors: Marc S Raab, Monika Engelhardt, Antje Blank, Hartmut Goldschmidt, Hermine Agis, Igor W Blau, Hermann Einsele, Barbara Ferstl, Natalie Schub, Christoph Röllig, Katja Weisel, Mark Winderlich, Janine Griese, Stefan Härtle, Johannes Weirather, Tiantom Jarutat, Christian Peschel, Manik Chatterjee
Journal: The Lancet Haematology (2020)
Treatment of advanced renal cell carcinoma with tumor lysate pulsed IL-12 secreting autologous dendritic cells
Authors: T. F. Wimpissinger, T. Felzmann, H. Hügel, P. Funovics, W. Stackl
Journal: Journal of Clinical Oncology (2006)

14585 Background: We have conducted a clinical phase I trial to evaluate feasibility and safety of dendritic cell-based immunotherapy in patients with advanced renal cell carcinoma (RCC). As opposed to previous cancer vaccination studies, dendritic cells were specifically enabled to secrete interleukin 12 (IL-12). Methods: Patients with advanced RCC (n = 11) received six weekly intranodal vaccinations with autologous monocyte-derived dendritic cells (mDCs). MDCs were loaded with autologous tumor cell lysate and were specifically stimulated to secrete IL-12 to polarize type-1 T-helper lymphocytes (Th1) and to directly present tumor antigens to cytotoxic T lymphocytes (CTL). Results: There was no significant treatment-related toxicity and no clinical evidence of autoimmunity. Vaccination was very well tolerated. Five patients had stable disease for at least five months, while four patients had progressive disease. Two patients with early clinically significant disease progression had to be excluded before completion of the treatment. In addition, we could detect enhanced anti-tumor immunity in vitro comparing immune response before versus after cancer vaccination. Conclusions: Our findings indicate that cancer vaccination with IL-12 secreting mDCs is well tolerated and has potential clinical and clear immunological effects in patients with advanced RCC. No significant financial relationships to disclose.
Cytokine levels in patients (pts) with localized colorectal cancer (CRC) after surgery and their relationship to fatigue and cognitive function
Authors: J. Vardy, S. Rourke, J. Galica, G. R. Pond, A. Park, H. Zhang, S. J. Clarke, H. Dhillon, L. Wagner, I. F. Tannock
Journal: Journal of Clinical Oncology (2006)

3623 Background: Cytokines have been associated with fatigue and cognitive dysfunction. Here we evaluate cytokine levels in pts with CRC as part of a longitudinal study evaluating these symptoms. Methods: Serum levels of 12 cytokines were measured using a LiquiChip assay on pts with localized CRC at baseline (mean 7 weeks post-surgery or before neoadjuvant therapy), 6 and 12 months. Group A (Stage III/high risk II) received chemotherapy (CT) and group B (Stage I/II) received no CT. Pts completed concurrent questionnaires for fatigue &amp; QOL (FACT-F), anxiety/depression (GHQ), and perception of cognitive function (FACT-COG); they had neuropsychological (NP) assessment with traditional tests and CANTAB, a computerized NP battery. Associations between cytokine levels, test results, demographic and disease-related factors were sought. Results: Baseline data are available for 82 pts: 65 group A and 17 group B, with follow-up at 6 and 12 months for 32 and 15 pts. Mean age was 58 years and 68% were male. Cytokine levels were elevated in all groups with larger ranges after surgery (selected data in table ); in healthy people they are generally undetectable. There was cognitive impairment at baseline in 28% on traditional NP tests. At 6 months CT pts had more fatigue (median FACT-F 43 vs 47), perceived more cognitive impairment (median FACT-COG 127 vs 138), and had more cognitive impairment on CANTAB (42% vs 17%), but not on traditional NP tests (32% vs 33%). At 6 months, elevated cytokines (IL-1,-6,-8,-12, TNF, IFN) were associated with greater deficit on CANTAB (p&lt;0.06); there was no association of cytokines with time from surgery, traditional NP test score, FACT-COG, fatigue, QOL or anxiety &amp; depression. Conclusions: Cytokine levels were elevated in most pts. Cognitive impairment is present in some pts prior to chemotherapy and CT pts have worse impairment on computerized NP tests than non-CT pts. Elevated cytokines may be associated with worse cognitive function. [Table: see text] No significant financial relationships to disclose.
TRIM33 prevents pulmonary fibrosis by impairing TGF-β1 signalling
Authors: Pierre-Marie Boutanquoi, Olivier Burgy, Guillaume Beltramo, Pierre-Simon Bellaye, Lucile Dondaine, Guillaume Marcion, Lenny Pommerolle, Aurélie Vadel, Maximilien Spanjaard, Oleg Demidov, Arnaud Mailleux, Bruno Crestani, Martin Kolb, Carmen Garrido, Françoise Goirand, Philippe Bonniaud
Journal: European Respiratory Journal (2020)

Idiopathic pulmonary fibrosis (IPF) is a devastating disease characterised by myofibroblast proliferation and abnormal extracellular matrix accumulation in the lungs. Transforming growth factor (TGF)-β1 initiates key profibrotic signalling involving the SMAD pathway and the small heat shock protein B5 (HSPB5). Tripartite motif-containing 33 (TRIM33) has been reported to negatively regulate TGF-β/SMAD signalling, but its role in fibrogenesis remains unknown. The objective of this study was to elucidate the role of TRIM33 in IPF.TRIM33 expression was assessed in the lungs of IPF patients and rodent fibrosis models. Bone marrow-derived macrophages (BMDM), primary lung fibroblasts and 3D lung tissue slices were isolated from Trim33-floxed mice and cultured with TGF-β1 or bleomycin (BLM). Trim33 expression was then suppressed by adenovirus Cre recombinase (AdCre). Pulmonary fibrosis was evaluated in haematopoietic-specific Trim33 knockout mice and in Trim33-floxed mice that received AdCre and BLM intratracheally.TRIM33 was overexpressed in alveolar macrophages and fibroblasts in IPF patients and rodent fibrotic lungs. Trim33 inhibition in BMDM increased TGF-β1 secretion upon BLM treatment. Haematopoietic-specific Trim33 knockout sensitised mice to BLM-induced fibrosis. In primary lung fibroblasts and 3D lung tissue slices, Trim33 deficiency increased expression of genes downstream of TGF-β1. In mice, AdCre-Trim33 inhibition worsened BLM-induced fibrosis. In vitro, HSPB5 was able to bind directly to TRIM33, thereby diminishing its protein level and TRIM33/SMAD4 interaction.Our results demonstrate a key role of TRIM33 as a negative regulator of lung fibrosis. Since TRIM33 directly associates with HSPB5, which impairs its activity, inhibitors of TRIM33/HSPB5 interaction may be of interest in the treatment of IPF.
Expression of cyclin D1 and p21(WAF1/CIP1) in human gastric carcinoma and its clinicopathologic significance.
Authors: Vasiliki Michalaki, Theodosios Theodosopoulos, Agathi Kondi- Pafiti, Constantine G. Gennatas
Journal: Journal of Clinical Oncology (2013)

e15114 Background: The deregulation of cyclin, cyclin-dependent kinases (CDKs) and their inhibitors could have a crucial role in the development of diverse human cancers. Alterations in cell cycle regulators and subsequent deregulation of the cell cycle are frequently involved in tumorigenesis and/or tumor progression. The aim of our study was to detect the abnormal expression of cyclin D1 and p21(WAF1/CIP1)in gastric carcinoma and investigate its clinicopathologic significance. Methods: Proteins of cyclin D1 were detected by immunohistochemistry in 80 cases of advanced gastric carcinoma, and 30 cases of benign gastric diseases (chronic gastritis, atrophic gastritis, gastric metaplasia, and gastric dysplasia). From each patient formaldehyde–fixed paraffin sections were stained and examined by immunohistochemistry using monoclonal antibodies.All tumor cells with distinct nuclear staining were considered positive. Results: Sixty-five patients were male and forty five female. Normal gastric epithelium showed consistently positive immunostain for p21WAF1/CIP1. Loss of p21WAF1/CIP1 expression was noted in 65% of intestinal type adenocarcinoma and in 90% of diffuse type adenocarcinoma. Overexpression of cyclin D1 was detected in 90% of advanced gastric carcinomas. Among the various clinicopathological findings, overexpression of cyclin D1 was associated with lymph-node metastasis (P=0.003) and recurrence (P=0.044). Loss of p21WAF1/CIP1 expression was more frequent in diffuse type cancers (P=0.005) and was correlated with recurrence (P=0.002) and death (P=0.001). Conclusions: These findings suggest that overexpression of cyclin D1 is a frequent finding in gastric cancer and immunohistochemical analysis for cell cycle regulators, might be a useful prognostic indicator in gastric cancer.