tbuckley/cabot-search huggingface dataset:
Abstract 433: Diagnostic targeted sequencing panel for hepatocellular carcinoma genomic screening
Authors: Viola Paradiso, Andrea Garofoli, Nadia Tosti, Valeria Perrina, Manuela Lanzafame, Luca Quagliata, Matthias S. Matter, Stefan Wieland, Markus H. Heim, Salvatore Piscuoglio, Charlotte K. Ng, Luigi M. Terracciano
Journal: Cancer Research (2018)

Abstract Commercially available targeted or exome panels miss some genes and regions frequently mutated in hepatocellular carcinoma (HCC); we aim to design and benchmark an HCC-specific panel as a robust high-throughput and cost-effective panel for genomic screening in HCC. We designed an Ion AmpliSeq panel targeting all exons of 33 liver cancer protein-coding genes, recurrently mutated long non-coding RNA genes MALAT1 and NEAT1, the recurrently mutated promoter regions of TERT, WDR74, MED16 and TFPI2, as well as mutation hotspots in 7 additional cancer genes. We profiled DNA from fresh frozen tumor (FFT, n=10, median depth 1495x) and/or formalin-fixed paraffin-embedded (FFPE) tumor with low input DNA (n=36, median depth 530x), and their non-tumoral counterparts from 39 HCCs using the custom panel. We benchmarked the somatic mutations and copy number alterations (CNAs) identified against those from Illumina whole-exome sequencing (WES) of the equivalent FFT samples (median depth 112x). At least one somatic mutation was identified in 35/39 cases using the custom panel. Median of 2.5 (0-74) and 3 (0-76) mutations were identified in FFT and FFPE samples, respectively. 98% (61/62) of the mutations identified from WES of the 10 FFT samples were successfully recovered using the custom panel, with the identification of an additional 6 and 32 mutations in coding and non-coding regions, respectively. Similarly, all 104 mutations identified from WES were also found based on the analysis of our custom panel of the 36 FFPE biopsies. We identified an additional 18 and 70 somatic mutations in coding and non-coding genes, respectively, using our custom panel, including 2 CTNNB1 activating mutations. Furthermore, copy number analysis revealed high correlation (r = 0.8) in the identification of gains/ amplifications and losses/ homozygous deletions in the genes included in the custom-panel between our custom panel and the WES. Here, we develop a robust high-throughput and cost-effective tool for HCC genomic screening that allows the identification with high sensitivity and specificity of somatic mutations as well as copy number alterations in routine diagnostic tissue specimens. Citation Format: Viola Paradiso, Andrea Garofoli, Nadia Tosti, Valeria Perrina, Manuela Lanzafame, Luca Quagliata, Matthias S. Matter, Stefan Wieland, Markus H. Heim, Salvatore Piscuoglio, Charlotte K. Ng, Luigi M. Terracciano. Diagnostic targeted sequencing panel for hepatocellular carcinoma genomic screening [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 433.
Abstract 11465: Ultrafast Cooling With Total Liquid Ventilation Attenuates Multi-organ Failure and Sepsis-like Response After Experimental Shock Induced by Aortic Cross Clamping
Authors: Nicolas Mongardon, Matthias Kohlhauer, Fanny Lidouren, Caroline Barau, Bruno Costes, Sébastien Giraud, Thierry Hauet, Pierre Carli, Benoit Vivien, Mathieu Nadeau, Philippe Micheau, Alain Cariou, Gilles Dhonneur, Alain Berdeaux, Bijan Ghaleh, Renaud Tissier
Journal: Circulation (2015)

Introduction: Total liquid ventilation (TLV) provides ultrafast cooling and potent neuro- and cardioprotection after experimental cardiac arrest. Hypothesis: We determined whether it could also mitigate multi-organ failure and sepsis-like response after abdominal ischemia/reperfusion and subsequent shock. Methods: Anesthetized rabbits were submitted to 30 min of supracoeliac aortic cross-clamping and 300 min of reperfusion. They underwent a normothermic procedure (Control group) or rapid cooling toward 32-33°C with TLV started either before, during or after aortic clamping (PRE, PER and POST groups, respectively). TLV was maintained during 75 min after which rabbits were rapidly rewarmed and switched to conventional mechanical ventilation. Results: Control animals elicited a dramatic shock state with a low cardiac output, high demand in norepinephrine, liver failure and acute kidney injury. Cardiac output was gradually improved in POST, PER and PRE groups as compared to Control (53±3, 64±5, 90±10 and 36±8 ml/min/kg after 300 min, respectively; all p&lt;0.05). A significant protection was also observed in the TLV groups regarding liver enzymes (ASAT, ALAT, L-FABP), acute kidney injury markers (nNAG, KIM-1, NGAL, β2-microglobulin) and renal function parameters (creatinine clearance and fractional Na+ excretion). The protection was maximal in the PRE group and achieved a lower extent in PER and POST groups when compared to Control. As example, urinary clearance of creatinine achieved 4.8±1.2, 1.3±0.9, 0.9±1.4 in PRE, PER and POST groups vs 0.5±0.4 ml/kg/min in Control (all p&lt;0.05), respectively. Importantly, multi-organ failure was associated with elevated blood transcripts of inflammatory markers (e.g., IL-1β, IL-8, IL-10). This was attenuated in all groups submitted to TLV with no difference between PRE, PER and POST groups. As example, changes in IL-1β achieved 2.7±0.4, 3.8±0.4 and 3.2±1.1 in PRE, PER and POST groups vs 5.6±0.7 in Control (fold-change from baseline; p&lt;0.05), respectively. Conclusions: Ultra-fast cooling with TLV attenuates shock and multi-organ failure in a model of abdominal ischemia/reperfusion. The cardiac, liver and renal protections but not anti-inflammatory effects depend upon the window of application.
Alterations of Heart Rate Variability After Radiofrequency Catheter Ablation of Focal Atrial Fibrillation Originating From Pulmonary Veins
Authors: Ming-HsiungHsieh, Chuen-WangChiou, Zu-ChiWen, Chieh-HungWu, Ching-TaiTai, Chin-FengTsai, Yu-AnDing, Mau-SongChang, Shih-AnnChen
Journal: Circulation (1999)

Background—Transient sinus bradycardia and hypotension have been reported as complications during radiofrequency (RF) ablation of focal atrial fibrillation (AF) originating from pulmonary veins (PVs). This study used heart rate variability (HRV) to evaluate the effects of focal PVs ablation on autonomic function. Methods and Results—Thirty-seven patients with paroxysmal AF were referred for ablation. The study group included 30 patients who underwent transseptal ablation of PVs, and the control group included 7 patients who underwent the transseptal procedure without ablation. The mean sinus rate and time-domain (standard deviation of RR intervals and root-mean-square of differences of adjacent RR intervals) and frequency-domain (low frequency, high frequency, and low-frequency/high-frequency ratio) analyses of HRV were obtained by use of 24-hour Holter monitoring before and 1 week, 1 month, and 6 months after ablation. All the triggering points of AF were from PVs, and they were successfully ablated. Sev...
Trophic Effect of Human Pericardial Fluid on Adult Cardiac Myocytes
Authors: StefanoCorda, AlexandreMebazaa, Maria-PiaGandolfini, CatherineFitting, FrançoiseMarotte, JacquelinePeynet, DanièleCharlemagne, Jean-MarcCavaillon, DidierPayen, LydieRappaport, Jane-LyseSamuel
Journal: Circulation Research (1997)

Abstract Pericardial fluid (PF) may contain myocardial growth factors that exert paracrine actions on cardiac myocytes. The aims of this study were (1) to investigate the effects of human PF and serum, collected from patients undergoing cardiac surgery, on the growth of cultured adult rat cardiac myocytes and (2) to relate the growth activity of both fluids to the adaptive changes in overloaded human hearts. Both PF and serum increased the rate of protein synthesis, measured by [14C]phenylalanine incorporation in adult rat cardiomyocytes (PF, +71.9±8.2% [n=17]; serum, +14.9±6.5% [n=13]; both P<.01 versus control medium). The effects of both PF and serum on cardiomyocyte growth correlated positively with the respective left ventricular (LV) mass. However, the magnitude of change with PF was 3-fold greater than with serum (P<.01). These trophic effects of PF were mimicked by exogenous basic fibroblast growth factor (FGF2) and inhibited by anti-FGF2 antibodies and transforming growth factor-β (TGF-β), sugges...
Abstract 14087: Cerebral Energy Metabolism Monitoring for Post Cardiac Arrest Prognostication
Authors: Minjung K Chae, Min Seob Sim, Min Jeong Lee, Sung Eun Lee
Journal: Circulation (2017)

Introduction: For patient specific interventions such as tailored targeted temperature management(TTM) for the on-going ischemia reperfusion injury of post cardiac arrest, objective serial assessment of severity of brain injury are needed. Global cerebral oxygenation and cerebral energy metabolism can be monitored and secondary brain injury can be detected by a catheter placed in the jugular bulb. Hypothesis: Cerebral energy metabolism monitoring obtained from arterio-jugular differences of metabolites will provide serial assessments of brain injury and correlate with patient neurologic outcomes. Methods: Blood gas analyses lactate and glucose was obtained every 6 hours from the radial artery and jugular bulb throughout TTM. We analyzed cerebral energy metabolism by serial measurements and assessed whether this can predict neurologic outcome. Reciever operation curve analysis was done to analyse the predictive values (AJDL,LOI,CEO2,AJCO2) obtained from arterio-jugular blood gas analyses, lactate and gluco...
Abstract 4476: Role of MAP-Kinase suppressor in IBD
Authors: Sharad Khare, Qiong Zhang
Journal: Cancer Research (2018)

Abstract BACKGROUND &amp; AIMS: Endogenous suppressor of Mitogen Activated Kinase Pathway (MAPK) are considered cancer suppressors. In this regard , Sprouty (SPRY) proteins that are endogenous suppressor of receptor tyrosine kinase signaling are reported to be tumor suppressors in various cancers, whereas we discovered that SPRY2 augments Epithelial Mesenchymal Transition (EMT) in colorectal cancer (CRC) [Oncogene, 2016 Jun 16; 35(24): 3151-62]. Significance of SPRY proteins in Inflammatory Bowel Disease (IBD) is not clearly understood. MATERIALS &amp; METHODS: Biopsies from Crohn's Colitis patients were assessed for SPRY, Beta-catenin, Occludin and ZO1 expression. Tight junction profiler was employed to assess expression of integrin proteins in CaCO2 colon cancer cell line. SPRY was suppressed in colon cancer cells by siRNA and CRISPR/Cas9 technology and changes were assessed by immunoblotting, real time PCR, phase-contrast and confocal microscopy. Spry1 and Spry2 floxed mice were utilized to dissect SPRY functions in mesenchymal cells. RESULTS: SPRY, E-cadherin, Beta-catenin and Occludin mRNA transcripts were significantly different in IBD patients (p&amp;lt;0.05). No significant changes in ZO1 mRNA transcripts were noted. Suppression of SPRY significantly decreased expression of several integrins in CaCO2 cells (p&amp;lt;0.05) . Treatment of CaCO2 cells with Dextran Sodium Sulfate (DSS) significantly altered SPRY, Beta-catenin, Occludin and ZO1 expressions that was reversed by SPRY suppression. Spry1-/- and Spry2-/- double mutant murine embryonic fibroblasts (MEFs) demonstrated restoration of several epithelial markers which protected cells from DSS-induced changes. CONCLUSIONS: SPRY expression in colonic epithelium regulates IBD. SPRY has prognostic value in IBD. Citation Format: Sharad Khare, Qiong Zhang. Role of MAP-Kinase suppressor in IBD [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4476.
Therapeutic mesopore construction on 2D Nb<sub>2</sub>C MXenes for targeted and enhanced chemo-photothermal cancer therapy in NIR-II biowindow
Authors: Xiaoxia Han, Xiangxiang Jing, Dayan Yang, Han Lin, Zhigang Wang, Haitao Ran, Pan Li, Yu Chen
Journal: Theranostics (2018)

Two-dimensional (2D) MXenes have emerged as a promising planar theranostic nanoplatform for versatile biomedical applications; but their in vivo behavior and performance has been severely influenced and hindered by a lack of necessary surface chemistry for adequate surface engineering. To solve this critical issue, this work employs versatile sol-gel chemistry for the construction of a unique "therapeutic mesopore" layer onto the surface of 2D niobium carbide (Nb2C) MXene. Methods: The in situ self-assembled mesopore-making agent (cetanecyltrimethylammonium chloride, in this case) was kept within the mesopores for efficient chemotherapy. The abundant surface saline chemistry of mesoporous silica-coated Nb2C MXene was further adopted for stepwise surface engineering including PEGylation and conjugation with cyclic arginine-glycine-aspartic pentapeptide c(RGDyC) for targeted tumor accumulation. Results: 2D Nb2C MXenes were chosen based on their photothermal conversion capability (28.6%) in the near infrared (NIR)-II biowindow (1064 nm) for enhanced photothermal hyperthermia. Systematic in vitro and in vivo assessments demonstrate targeted and enhanced chemotherapy and photothermal hyperthermia of cancer (U87 cancer cell line and corresponding tumor xenograft; inhibition efficiency: 92.37%) in the NIR-II biowindow by these mesopore-coated 2D Nb2C MXenes. Conclusion: This work not only significantly broadens the biomedical applications of 2D Nb2C MXene for enhanced cancer therapy, but also provides an efficient strategy for surface engineering of 2D MXenes to satisfy versatile application requirements.
Abstract 5024: Drug screening of biopsy-derived multicellular spheroids using microfluidic technology
Authors: Theresa E. Mulholland, Milly McAllister, Samantha Patek, David Flint, Mark Underwood, Alexander Sim, Joanne Edwards, Michele Zagnoni
Journal: Cancer Research (2018)

Abstract Performing drug screening, of physiologically relevant three-dimensional (3D) tumor models, for personalized treatment remains challenging, due to the small amount of tissue available from most biopsies. New microfluidic technologies, enabling greater control over cell positioning and fluid behavior at the micro-scale, allow extensive testing of anticancer agents on human tumor tissue preparations in 3D and offer new solutions for the development of anticancer compounds and personalized medicine. We have developed a microfluidic platform for extensive drug screening of tumor biopsies in a cost-effective manner and validated the system with tumor prostate patient samples. As a typical drug screening assay, up to 22 drug concentration-response curves could be generated from a single biopsy, within a time frame of up to 4 weeks. Biopsy tissue, grown as a heterogeneous co-culture from the primary sample, was prepared as cancer-cell enriched multicellular spheroids, cultured for 3 to 5 days prior to the application of a panel of standard-of-care drugs for prostate cancer. Readouts were obtained via bright-field and epifluorescence microscopy. The microfluidic platform was designed to be operated entirely without the need of external fluid actuation, with the microfluidic network capable of generating long-lasting, stable and repeatable drug concentration gradients across arrays of 240 spheroids. Outcomes were generated as 8-point drug concentration response curves per device, with each drug concentration tested on at least 24 spheroids. In-house developed software was used to analyze bright-field and fluorescent images to provide readouts of spheroid growth and viability, as well as information on drug penetration and drug efficacy over time. Following platform and assay validation using cancer cell lines, proof-of-concept screening was performed on prostate biopsies from 2 different patients. Results showed that biopsy-derived spheroids were more resistant to treatment than LNCaP spheroids, a prostate cancer cell line. For one biopsy, spheroids were sensitive to docetaxel, but resistant to enzalutamide, despite the presence of intact androgen receptors. This preliminary data outlines how this technology could become a useful tool to investigate patient-specific drug resistance and to test novel anticancer agents in a cost-effective manner, based on maximized screening of human tumor tissue in a 3D format. Citation Format: Theresa E. Mulholland, Milly McAllister, Samantha Patek, David Flint, Mark Underwood, Alexander Sim, Joanne Edwards, Michele Zagnoni. Drug screening of biopsy-derived multicellular spheroids using microfluidic technology [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5024.
Abstract 20030: Reperfusion Therapy With Rapamycin Prevents Myocardial Injury in Type 2 Diabetic Rabbits
Authors: Arun Samidurai, Ramzi A Ockaili, Scott M Filippone, Rakesh C Kukreja, Anindita Das
Journal: Circulation (2016)

Background: A sustained hyperactive mammalian target of rapamycin (mTOR) leads to diabetic complication with cardiovascular disease through stimulation of oxidative stress and inflammatory response...
Abstract 15249: Loss of Early Vasodilator Response at the Brachial Artery Predicts the Presence of Critical Coronary Stenoses
Authors: Salvatore De Rosa, Concetta Irace, Giuseppe Ambrosio, Claudio Carallo, Caterina Covello, Cesare Tripolino, Clarice Gareri, Ennio Abramo, Ciro Indolfi, Agostino Gnasso
Journal: Circulation (2015)

Cardiovascular diseases (CVD) are the leading cause of mortality and morbidity in Western Countries. Coronary artery disease is the etiology underlying the most prevalent clinical manifestations of CVD. Atherosclerosis is often diagnosed only at late stages, when it manifests in clinically overt forms. Coronary angiography often does not show critical stenoses. We recently showed that the latency of flow mediated dilation (FMD) correlates with the presence of carotid atherosclerosis and the individual cardiovascular risk. Hence, we aimed at evaluating whether the latency of the vasodilator response at the brachial artery could predict the presence of critical coronary stenoses. We evaluated FMD in 74 consecutive patients, before performing coronary angiography for clinical indication at our hospital. Patients were classified in early (ED), late (LD) and no dilators (ND), based on the latency of the vasodilator response. Briefly, ED showed maximal dilation at 60s after ischemic stimulus, and LD over 60s. Very interestingly, lost of early vasodilator response showed a much better diagnostic performance than maximal FMD for the prediction of critical (&gt;70%) coronary stenoses. In fact, classification match of loss of early vasodilator response with coronary angiography was twice as good as with FMD max (72% vs 39%, p=0.002). Using this approach, the number of false negative results was quite low at 4/74 (0.5%), yielding a 89% specificity. Furthermore, ischemia extension - measured by means of the Gensini score - was progressively larger with longer latency (4.5±13.5 in ED, 17.5±27.1 in LD, 39.7±55.0 in ND; p&lt;0.02). In conclusion, using the lost of early vasodilator response as a diagnostic cutpoint allowed to confidently rule out the presence of critical coronary stenoses be means of a simple non-invasive examination. In our cohort, this could have avoided a useless exposition of patients to the potential complications of an invasive coronary angiography in 42% of cases. Once confirmed in larger studies, measurement of latency in vasodilator response could largely improve the selection of patients to refer for coronary angiography, reducing useless patients’ exposition to a potentially harmful diagnostic procedure and healthcare costs.
Medical Therapy Alone Produces Regression of Combined Aortic and Mitral Valve Involvement in Hypereosinophilic Syndrome
Authors: TetsushiYamamoto, TetsuariOnishi, AkihiroKaneko, KensukeMatsumoto, NobuhideHayashi, ShohiroKinoshita, SeijiKawano, HiroyaKawai, Ken-ichiHirata, ShunichiKumagai
Journal: Circulation (2010)
Abstract 5080: ADAM10 promotes breast cancer via CXCL16 constitutive cleavage and CXCR6 signaling
Authors: Dominique N. Gales, Hina Mir, Neeraj Kapur, James W. Lillard, Shailesh Singh
Journal: Cancer Research (2018)

Abstract Despite the survival of breast cancer (BrCa) patients, there is still demand to better understand metastasis as the obvious mark for most aggressive breast cancers. Recent evidence highlighted the possible involvement of chemokines and their cognate receptors in BrCa progression and metastasis. Expression and functional role of CXCR6 and CXCL16 have been investigated in different types of cancer. ADAM10 is also known to regulate the metastatic process by the proteolytic shedding of CXCL16 creating a soluble form of CXCL16. High levels of soluble CXCL16 could support tumor progression by promoting migration and invasion of CXCR6 expressing BrCa cells. Here, we demonstrate the significance of CXCR6-CXCL16 axis in BrCa progression. In addition to increased CXCR6 expression, our tissue microarray analysis (TMA) showed increased expression of CXCL16 and ADAM10 in BrCa tissues. BrCa cell lines (MCF-7 and MBA-231) also showed higher expression of ADAM10 as compared to the normal epithelial cells (MCF-10A). Further, these BrCa cells showed increased migration and invasion towards CXCL16 gradient that is due to high expression of CXCR6 and ADAM10. Hence, our findings suggest the clinical and biological significance of ADAM10 and soluble CXCL16 in BrCa progression. We also highlight the potential of ADAM10 and soluble CXCL16 as prognostic markers and new therapeutic target for BrCa. Citation Format: Dominique N. Gales, Hina Mir, Neeraj Kapur, James W. Lillard, Shailesh Singh. ADAM10 promotes breast cancer via CXCL16 constitutive cleavage and CXCR6 signaling [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5080.