tbuckley/cabot-search huggingface dataset:
Abstract 3661: Comparison of ctDNA markers in matched urine and plasma from patients with liver cancer
Authors: Tai-Jung Lee, Surbhi Jain, Jamin D. Steffen, Adam M. Zhang, Chi-Tan Hu, James P. Hamilton, Ying-Hsiu Su
Journal: Cancer Research (2018)

Abstract Hepatocellular carcinoma (HCC) is the fourth leading cause of cancer worldwide and a leading cause of global cancer mortality. Lack of efficient early detection and limited therapeutic options are two key contributing factors for the dismal prognosis of this disease. We have previously shown that urine contains fragmented, circulation-derived cell-free DNA that can be used for detection of circulating tumor DNA (ctDNA) if a tumor is present, suggesting urine as an alternative body fluid to plasma for cancer liquid biopsy. This study compared the detectability of five known HCC-associated DNA modifications, including genetic mutations (TERT -124 G&amp;gt;A, TP53 249 G&amp;gt;T and CTNNB1 hotspot at codon 32-45) and epigenetic methylation (mGSTP1, mRASSF1A), in matched urine and plasma from patients with liver cancer. In order to increase the sensitivity of detecting DNA modifications from the short, fragmented DNA templates, specialized short amplicon PCR assays were developed. To compare the detectability of HCC ctDNA markers in urine and plasma, 26 pairs of urine and plasma samples from HCC patients were identified and tested for five HCC ctDNA markers. In this cohort, 17 of 26 (65%) HCC samples had serum AFP above 20 ng/mL and were considered AFP-positive HCC. By using our HCC DNA biomarker panel composed of 5 assays, 22/26 (84.6%) urine and 23/26 (88.5%) plasma samples were found to have at least one DNA marker detected. In the combination of our HCC DNA biomarker panel with serum-AFP, the sensitivity of HCC detection in a liquid biopsy of urine and plasma as compared to serum-AFP alone (the current most used screening marker) increased from 65% to 92.3% for both urine plus AFP and plasma plus AFP. Further studies to include non-HCC samples (such as cirrhosis) to determine the specificity of the HCC DNA biomarker panel for liquid biopsy are in progress. In conclusion, our research provides the promising potential for HCC liquid biopsy screening in at-risk populations and precision medicine by using plasma, urine, or both as body fluids. Citation Format: Tai-Jung Lee, Surbhi Jain, Jamin D. Steffen, Adam M. Zhang, Chi-Tan Hu, James P. Hamilton, Ying-Hsiu Su. Comparison of ctDNA markers in matched urine and plasma from patients with liver cancer [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 3661.
Activated Platelets Induce Monocyte Chemotactic Protein-1 Secretion and Surface Expression of Intercellular Adhesion Molecule-1 on Endothelial Cells
Authors: MeinradGawaz, Franz-JosefNeumann, TimmDickfeld, WernerKoch, Karl-LudwigLaugwitz, HelmutAdelsberger, KirstenLangenbrink, SharonPage, DieterNeumeier, AlbertSchömig, KorbinianBrand
Journal: Circulation (1998)

Background—Platelet/endothelium interaction plays an important role in the pathophysiology of inflammation and atherosclerosis. The role of platelets for monocyte chemotactic protein-1 (MCP-1) secretion and surface expression of intercellular adhesion molecule-1 (ICAM-1) on endothelial cells has been assessed. Methods and Results—Monolayers of human umbilical vein endothelial cells were incubated with nonstimulated or ADP-activated platelets for 6 hours, and secretion of MCP-1 and surface expression of ICAM-1 were determined by ELISA and flow cytometry, respectively. In the presence of ADP-activated platelets, both MCP-1 secretion and ICAM-1 surface expression were significantly increased compared with nonstimulated platelets (P<0.02). Activation of the transcription factor nuclear factor-κB (NF-κB) determined by electrophoretic mobility shift assay and κB-dependent transcriptional activity was enhanced in the presence of activated platelets. In addition, ADP-activated platelets induced MCP-1 and ICAM-1 p...
Abstract 18729: Prosthetic Valve Positioning - Not a Static Question
Authors: Hurst M Hall
Journal: Circulation (2015)

A 65-year-old female with a history of bicuspid aortic valve s/p AVR with a Medtronic Hall mechanical valve presented with chest pain. Her recent history was notable for one week of intermittent substernal chest pain present when lying in the left lateral position. Initial ECG, obtained during an episode of chest pain, revealed 2 mm ST segment depression in the anterolateral leads and ST segment elevation in lead aVR. The ECG changes normalized with cessation of her chest pain. Laboratory evaluation showed an INR of 3.5 (on warfarin), and normal cardiac biomarkers. Chest imaging, including CT angiography, was unremarkable. Physical examination demonstrated a normal jugular venous pressure, a mechanical second heart sound, and a II/VI crescendo-decrescendo systolic murmur at the right upper sternal border. Transthoracic echocardiography (TTE) revealed normal biventricular systolic function and a mechanical valve in the aortic position, associated with mild aortic regurgitation. Valve fluoroscopy revealed an aortic monoleaflet mechanical prosthesis with normal opening and closing angles in the supine position, but with closing restriction when in the left lateral decubitus position (closing angle 46 degrees, associated with recurrent chest pain and ischemic ECG changes). Transesophageal echocardiography (TEE) showed moderate aortic stenosis, mild aortic regurgitation, and multiple linear echodensities on the aortic prosthesis. These echogenicities were felt to represent thrombi, and the patient was treated with 5 doses of tPA and intravenous heparin. Subsequent TEE and valve fluoroscopy revealed improved prosthetic leaflet motion in supine and lateral decubitus positions. This case describes an unusual presentation of mechanical aortic valve thrombosis. The contiguous association of the mechanical valve with the coronary ostia can contribute to ischemic complications, in this case positionally induced. It also highlights the value of timely valve fluoroscopy and the consideration of patient maneuvers to delineate valve function. Current guidelines support the use of thrombolytic therapy for small, left-sided thrombi, with recent literature suggesting that slowly infused low-dose tPA provides the optimal risk-benefit profile.
Abstract 3194: Development of anin vitrodrug profiling platform with primary Rhabdomyosarcoma cells for tailoring patient-specific treatments
Authors: Marco Wachtel, Gabriele Manzella, Michaela Römmele, Luduo Zhang, Joelle Tchinda, Felix Niggli, Beat Schäfer
Journal: Cancer Research (2018)

Abstract The paradigm of cancer therapy currently shifts from broadly used cytotoxic drug cocktails to patient specific precision therapies. These novel therapies are normally directed towards tumor specific driver oncogenes, identified by genomic analysis of individual tumors. In case of tumors with a very low mutational burden and/or currently undruggable driver oncogenes this approach is less suitable. There, direct drug profiling of in vitro cultured tumor cells represents a promising alternative for identification of patient specific therapies. Conditions to maintain primary tumor cells in culture for this purpose however are largely unknown for most tumor entities. Here, we aimed to establish an in vitro drug profiling platform for Rhabdomyosarcoma (RMS), a childhood cancer with above described characteristics. Towards this aim, we isolated cells from 6 alveolar and 8 embryonal RMS patient derived xenografts and systematically tested 18 different culture conditions in order to find suitable parameters for in vitro propagation of primary RMS cells. This approach revealed that cells from most tumors survive and proliferate only in serum-free medium, whereas in serum containing medium tumor cells are progressively lost over time. Importantly, cells preserve the clonal composition and phenotypic characteristics of the primary PDX under these conditions, as assessed by genomic and copy number analysis. Drug profiles established with a library of 204 drugs revealed, beside patient-specific vulnerabilities, a yet unrecognized sensitivity of a subgroup of alveolar RMS towards AKT inhibitors. Furthermore, screening with the same drugs for resensitization of resistant relapse samples identified the BCL-2 family inhibitor ABT-263 as most potent resensitizer towards standard-of-care chemotherapy. Detailed molecular analysis revealed that this effect is based on blockade of the BCL-XL-MCL-1 axis. Overall, our proof of concept study highlights the feasibility of in vitro drug profiling of primary RMS cells for patient-specific treatment selection in a co-clinical setting. Citation Format: Marco Wachtel, Gabriele Manzella, Michaela Römmele, Luduo Zhang, Joelle Tchinda, Felix Niggli, Beat Schäfer. Development of an in vitro drug profiling platform with primary Rhabdomyosarcoma cells for tailoring patient-specific treatments [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 3194.
Novel Biochemical Diagnostic Method for Aortic Dissection
Authors: ToruSuzuki, HirohisaKatoh, MasafumiWatanabe, MasahikoKurabayashi, KatsuhikoHiramori, ShingoHori, MasakiyoNobuyoshi, HiromitsuTanaka, KazuhisaKodama, HikaruSato, ShinSuzuki, YasuhiroTsuchio, YoshioYazaki, RyozoNagai
Journal: Circulation (1996)

Background Aortic dissection is one of the most common aortic catastrophes. Although newer diagnostic methods as exemplified by image diagnostic techniques have greatly improved the diagnosis of aortic dissection, the diagnosis is still frequently missed today because the signs and symptoms of the disease are at times obscure. A reliable biochemical diagnostic method for aortic dissection would be beneficial. Methods and Results A novel biochemical diagnostic method for diagnosis of aortic dissection was developed that uses an immunoassay of monoclonal antibodies to smooth muscle myosin heavy chain. A prospective study was conducted to ascertain the usefulness of the method in the diagnosis of aortic dissection. Twenty-seven patients with aortic dissection admitted within the first 24 hours after onset were enrolled. Serial assay of serum smooth muscle myosin heavy chain showed significant elevations within the first 24 hours after onset of aortic dissection, with levels exceeding 10 ng/mL, with subsequen...
Mobile Automated External Defibrillator Response System during Road Races
Authors: Tomoya Kinoshi, Shota Tanaka, Ryo Sagisaka, Takahiro Hara, Toru Shirakawa, Etsuko Sone, Hiroyuki Takahashi, Masaru Sakurai, Akira Maki, Hiroshi Takyu, Hideharu Tanaka
Journal: New England Journal of Medicine (2018)

Mobile AED Response System during Road Races In Japan, an automated external defibrillator (AED) response system for runners included paramedics on bicycles who carried AEDs, on-foot teams, and a c...
Questioning Prediction of Lumbar Spine Surgery Outcome—Why We Need to Pay Attention
Authors: Philippe Rigoard, Amine Ounajim, Richard B. North
Journal: JAMA Surgery (2018)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Surgery HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Surgery journal
Overexpression of Transforming Growth Factor-β1 Stabilizes Already-Formed Aortic Aneurysms
Authors: JianpingDai, FranckLosy, Anne-MarieGuinault, CarinePages, IgnacioAnegon, PascalDesgranges, Jean-PierreBecquemin, EricAllaire
Journal: Circulation (2005)

Background— The cell response to transforming growth factor-β1 (TGF-β1), a multipotent cytokine with healing potential, varies according to tissue context. We have evaluated the ability of TGF-β1 overexpression by endovascular gene therapy to stabilize abdominal aortic aneurysms (AAAs) already injured by inflammation and proteolysis. Methods and Results— Active TGF-β1 overexpression was obtained in already-developed experimental AAAs in rats after endovascular delivery of an adenoviral construct encoding for a mutated form of active simian TGF-β1 and in an explant model using human atherosclerotic AAA fragments incubated with recombinant active TGF-β1. Transient exogenous TGF-β1 overexpression by endovascular gene delivery was followed by induction of endogenous rat TGF-β1. Overexpression of active TGF-β1 in experimental AAAs was associated with diameter stabilization, preservation of medial elastin, decreased infiltration of monocyte-macrophages and T lymphocytes, and a decrease in matrix metalloproteina...
Implantation of Bone Marrow Mononuclear Cells Into Ischemic Myocardium Enhances Collateral Perfusion and Regional Function via Side Supply of Angioblasts, Angiogenic Ligands, and Cytokines
Authors: HiroshiKamihata, HiroakiMatsubara, TakashiNishiue, SoichiroFujiyama, YoshiakiTsutsumi, RyozoOzono, HiroyaMasaki, YasukiyoMori, OsamuIba, ErikoTateishi, AtsushiKosaki, SatoshiShintani, ToyoakiMurohara, TsutomuImaizumi, ToshijiIwasaka
Journal: Circulation (2001)

Background Bone marrow implantation (BMI) was shown to enhance angiogenesis in a rat ischemic heart model. This preclinical study using a swine model was designed to test the safety and therapeutic effectiveness of BMI. Methods and Results BM-derived mononuclear cells (BM-MNCs) were injected into a zone made ischemic by coronary artery ligation. Three weeks after BMI, regional blood flow and capillary densities were significantly higher (4.6- and 2.8-fold, respectively), and cardiac function was improved. Angiography revealed that there was a marked increase (5.7-fold) in number of visible collateral vessels. Implantation of porcine coronary microvascular endothelial cells (CMECs) did not cause any significant increase in capillary densities. Labeled BM-MNCs were incorporated into ≈31% of neocapillaries and corresponded to ≈8.7% of macrophages but did not actively survive as myoblasts or fibroblasts. There was no bone formation by osteoblasts or malignant ventricular arrhythmia. Time-dependent changes in ...
A novel algorithm applicable to cancer next-generation sequencing panels to predict total tumor mutation load and correlation with clinical outcomes in melanoma.
Authors: Jason Roszik, Aron Joon, Alan Siroy, Lauren Elaine Haydu, Franceso Stingo, Veera Baladandayuthapani, Patrick Hwu, Michael T. Tetzlaff, Jennifer Ann Wargo, Jie Qing Chen, Laszlo George Radvanyi, Chantale Bernatchez, Jeffrey E. Gershenwald, Alexander J. F. Lazar, Michael A. Davies, Scott Eric Woodman
Journal: Journal of Clinical Oncology (2015)

9071 Background: Next-generation sequencing (NGS) panels of cancer-related genes are increasingly utilized in oncology. We developed an algorithm to estimate total tumor mutation burden in melanoma using genes present in local and commercial NGS panels. The algorithm was validated using independent datasets and analyzed for clinical significance in two cohorts of advanced melanoma patients (pts). Methods: Overlapping genes (n = 170) from two NGS panels were used for algorithm development. Publicly available whole exome sequencing (WES) data (n = 345) from the cutaneous melanoma TCGA was employed to develop a mutation score for each gene in the panel. The summation of the mutation scores yields the Predicted Total Mutation Load (PTML) of the tumor. The algorithm was applied to 3 independent melanoma WES datasets to test the correlation of predicted with actual mutation burden. The PTML was then determined for cohorts of melanoma pts treated with immune-therapy regimens (e.g., adoptive cell transfer (ACT)), and associations with clinical outcomes were determined. Results: The PTML correlated strongly with the actual WES mutation load of each tumor in all 3 tested melanoma WES datasets (Set 1, n = 121, r2 = 0.58; Set 2, n = 64, r2 = 0.84; Set 3, n = 127, r2 = 0.93). For subsequent analyses low PTML was defined as ≤ 100, and high as > 100 based on observed distributions. High PTML predicted both increased PFS (n = 36, p < 0.05) and OS (n = 35, p < 0.05) among pts treated with ACT. Pts with high PTML also had a longer interval from stage III to stage IV (n = 55, p < 0.05) and improved OS from stage IV (n = 62, p < 0.01) in a large cohort of MDACC patients with NGS data. Further testing demonstrated that accurate disease-specific PTML algorithms for other cancers (e.g., lung) are feasible. Conclusions: In this proof of concept study, a novel algorithm applied to NGS panels accurately predicted total mutation burden in cutaneous melanoma pts. High PTML ( > 100 mutations) correlated with improved OS in two cohorts of melanoma pts, including pts treated with immunotherapy. These results support further testing of the PTML algorithm in risk assessment and management of melanoma pts.
Abstract 1072: Potential biomarkers correlated with poor survival rate of melanoma patients
Authors: Alice S. Morais, Ana C. Monteiro, Fernando Andrade, Lucas Goedert, Enilza Espreáfico, Regine Schneider-Stock, André Fujiota, Miriam G. Jasiulionis
Journal: Cancer Research (2018)

Abstract Malignant melanoma is an extremely aggressive tumor, responsible for 90% of skin cancer mortality. Widespread metastasis is the main cause of death in melanoma patients. Therefore, the identification of molecules related to the degree of melanoma malignancy could be used as prognostic biomarkers. In the present study, using a murine model of melanoma progression, different genes, such as Snai1, Chd1, Gata4, Id4, Cbs, Vav1, and Itga4, were first identified as presenting aberrant DNA methylation in their promoters along melanoma progression by Methylight analysis. The gene expression pattern and epigenetic regulation were validated in these murine cell lines by RT-qPCR and 5AzaCdR treatment, respectively. The genes Angpt2 and Fgf1 were also identified as differentially expressed along tumor progression in this murine model. The expression profile of these genes was also evaluated in primary human melanocytes and RGP (radial growth phase), VGP (vertical growth phase) and metastatic melanoma cell lines. Clinical and gene expression data from 460 patients were obtained from TCGA (The Cancer Genome Atlas). Using an univariate test, patients presenting tumors with low levels of Chd1, Vav1, Id4 and Fgf1, and high levels of Snai1 and Angpt2 were shown to exhibit poor overall survival rate. Indeed, the multivariate analysis using Cox regression model identified high Snai1 (HR=1.217; 95% CI 1.075-1.377; p=0.002) and Angpt2 (HR=1.186; 95% CI 1.059-1.329; p=0.003) expression and low Chd1 (HR=0.757; 95% CI 0.575-0.996; p=0.047), Fgf1 (HR=0.858; 95% CI 0.780-0.944; p=0.002) and Vav1 (HR=0.859; 95% CI 0.764-0.967; p=0.011) expression as independent prognostic factors for the overall survival rate of patients with melanoma. Also using a multivariate analysis, the low levels of Id4 promoter methylation (HR=0.689; 95% CI 0.531-0.891; p=0.045) was shown to be an independent predictive factor for poor survival rate, although no correlation was found between Id4 expression and survival rate. In conclusion, the upregulation of Snai1 and Angpt2, and the downregulation of Chd1, Vav1 and Fgf1 are associated with unfavorable survival outcome, indicating they might be valuable prognostic biomarkers for melanoma. Supported by CNPq and FAPESP. Citation Format: Alice S. Morais, Ana C. Monteiro, Fernando Andrade, Lucas Goedert, Enilza Espreáfico, Regine Schneider-Stock, André Fujiota, Miriam G. Jasiulionis. Potential biomarkers correlated with poor survival rate of melanoma patients [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 1072.
Inflammatory Cytokines and Postmyocardial Infarction Remodeling
Authors: MinNian, PaulLee, NeelamKhaper, PeterLiu
Journal: Circulation Research (2004)

Inflammatory response and cytokine elaboration are particularly active after myocardial infarction and contribute to cardiac remodeling and eventual host outcome. The triggers of cytokine release in the acute postinfarction period include mechanical deformation, ischemic stimulus, reactive oxygen species (ROS), and cytokine self-amplification pathways. Acutely, the elaboration of tumor necrosis factor, IL-1 and IL-6, transforming growth factor families of cytokines, contribute to survival or deaths of myocytes, modulation of cardiac contractility, alterations of vascular endothelium, and recruitment of additional circulating cells of inflammation to the injured myocardium. This leads to further local oxidative stress and remodeling but also initiates the processes of wound healing. Chronically, sustained presence of cytokines leads to myocyte phenotype transition and activation of matrix metalloproteinases that modifies interstitial matrix, augmenting further the remodeling process. This in turn alters th...
Rapid Reversal of the Diabetic Endothelial Dysfunction by Pharmacological Inhibition of Poly(ADP-Ribose) Polymerase
Authors: Francisco GarciaSoriano, PálPacher, JonMabley, LucasLiaudet, CsabaSzabó
Journal: Circulation Research (2001)

Oxygen- and nitrogen-derived free radicals and oxidants play an important role in the pathogenesis of diabetic endothelial dysfunction. Recently we proposed the importance of oxidant-induced DNA strand breakage and activation of the nuclear enzyme poly(ADP-ribose) polymerase (PARP) in the pathogenesis of diabetic endothelial dysfunction. In this study, we tested whether established diabetic endothelial dysfunction is reversible by PARP inhibition. The novel PARP inhibitor PJ34 (10 mg/kg per day PO) was given at various lengths (4 weeks or 3 days) for established streptozotocin-diabetic animals. In addition, we also tested whether incubation of the aortic rings with PJ34 (3 μmol/L) or a variety of other PARP inhibitors for 1 hour affects the diabetic vascular changes. Both 4-week and 3-day PARP-inhibitor treatment of streptozotocin-diabetic mice with established endothelial dysfunction fully reversed the acetylcholine-induced endothelium-dependent relaxations in vitro. Furthermore, 1-hour in vitro incubati...
ACC/AHA 2005 Practice Guidelines for the Management of Patients With Peripheral Arterial Disease (Lower Extremity, Renal, Mesenteric, and Abdominal Aortic)
Authors: Alan T. Hirsch, Ziv J. Haskal, Norman R. Hertzer, Curtis W. Bakal, Mark A. Creager, Jonathan L. Halperin, Loren F. Hiratzka, William R.C. Murphy, Jeffrey W. Olin, Jules B. Puschett, Kenneth A. Rosenfield, David Sacks, James C. Stanley, Lloyd M. Taylor, Christopher J. White, John White, Rodney A. White
Journal: Circulation (2006)