tbuckley/cabot-search huggingface dataset:
Abstract 13597: The Association Between Tissue Morphology Assessed With Optical Coherence Tomography and Mid-term Results After Paclitaxel-coated Balloon Dilatation
Authors: TakeshiTada, KazushigeKadota, SeijiHabara, HiroyukiTanaka, YasushiFuku, TsuyoshiGoto, KazuakiMitsudo
Journal: Circulation (2014)

Introduction: It was reported that mid-term results after paclitaxel-coated balloon (PCB) dilatation for in-stent restenosis (ISR) lesions might differ depending on the tissue morphology of ISR lesions assessed with optical coherence tomography (OCT). It was also reported that ISR lesions after drug-eluting stent (DES) implantation was associated with poorer mid-term outcomes compared with those after bare-metal stent (BMS) implantation after PCB dilatation. The aim of this study was to define the impact of OCT findings on recurrence of ISR after PCB dilatation. Methods: Between October 2008 and December 2013, we performed percutaneous coronary intervention for 210 ISR lesions in 180 patients using PCB (143 men, mean age 68.8±9.4 years). The restenotic tissue structure at the minimum lumen area site (homogeneous, heterogeneous, or layered type) was assessed with OCT. We examined the association between tissue structure and acute/mid-term (6-8 months) results including acute gain, late loss, ISR and target...
Bone Marrow Monocyte Lineage Cells Adhere on Injured Endothelium in a Monocyte Chemoattractant Protein-1–Dependent Manner and Accelerate Reendothelialization as Endothelial Progenitor Cells
Authors: SoichiroFujiyama, KatsuyaAmano, KazutakaUehira, MasayukiYoshida, YasunobuNishiwaki, YoshihisaNozawa, DenanJin, ShinjiTakai, MizuoMiyazaki, KensukeEgashira, TakayukiImada, ToshijiIwasaka, HiroakiMatsubara
Journal: Circulation Research (2003)

Peripheral blood (PB)-derived CD14+ monocytes were shown to transdifferentiate into endothelial cell (EC) lineage cells and contribute to neovascularization. We investigated whether bone marrow (BM)- or PB-derived CD34−/CD14+ cells are involved in reendothelialization after carotid balloon injury. Although neither hematopoietic nor mesenchymal stem cells were included in human BM-derived CD34−/CD14+ monocyte lineage cells (BM-MLCs), they expressed EC-specific markers (Tie2, CD31, VE-cadherin, and endoglin) to an extent identical to mature ECs. When BM-MLCs were cultured with vascular endothelial growth factors, hematopoietic markers were drastically decreased and new EC-specific markers (Flk and CD34) were induced. BM-MLCs were intra-arterially transplanted into balloon-injured arteries of athymic nude rats. When BM-MLCs were activated by monocyte chemoattractant protein-1 (MCP-1) in vivo or in vitro, they adhered onto injured endothelium, differentiated into EC-like cells by losing hematopoietic markers,...
Abstract 10029: Six and Twelve-month Clinical and Imaging Results of the Multicenter First-in-man BIOSOLVE-I Study with the Paclitaxel-Eluting Bioabsorbable Magnesium Scaffold (DREAMS)
Authors: Michael Haude, Raimund Erbel, Paul Erne, Stefan Verheye, Paul Vermeersch, Hubertus Degen, Ron Waksman, Neil Weissman, Francesco Prati, Jacques Koolen
Journal: Circulation (2012)

Background Absorbable metal scaffolds (AMS) are developed to overcome limitations of current permanent bare or drug-eluting coronary stents like stent thrombosis despite prolonged dual antiplatelet therapy, caged vessel segment not allowing vasomotion and remodelling or chronic vessel wall inflammation. Magnesium is an essential element of the human body, thus it is considered as a potential alloy for absorption. To overcome the limitations associated with the first generation of a bare AMS a Drug (Paclitaxel) Eluting Absorbable Magnesium Scaffold was developed (DREAMS). Methods Forty-six subjects were enrolled in the BIOSOLVE-I study, and assigned to two cohorts with different follow-up schedules. Clinical follow-up for both cohorts was scheduled at 1, 6, 12, 24 and 36 months, angiographic and IVUS follow-up for cohort 1 at 6 and for cohort 2 at 12 months. A subgroup of patients underwent OCT and vasomotion testing. The primary endpoint is Target Lesion Failure (TLF), a composite of cardiac death, target...
Abstract 20107: Randomized Comparison of Personalized versus Standardized Substrate Modification During Catheter Ablation for Symptomatic Atrial Fibrillation
Authors: Simon Kircher, Arash Arya, David Altmann, Sascha Rolf, Andreas Bollmann, Philipp Sommer, Sergio Richter, Ole Breithardt, Borislav Dinov, Daniela Husser, Charlotte Eitel, Thomas Gaspar, Christopher Piorkowski, Gerhard Hindricks
Journal: Circulation (2015)

Introduction: Pulmonary vein (PV) isolation forms the cornerstone of any ablation procedure for atrial fibrillation (AF). There is, however, no uniform strategy how to detect and target left atrial (LA) arrhythmogenic substrate outside the PV antra. Fibrosis that corresponds well to LA low-voltage areas (LVAs) seems to play a key role in AF arrhythmogenesis and might therefore be a suitable target for additional substrate modification (SM). Objective: The purpose of this prospective randomized study was to compare a novel technique for SM based on ablation of potentially arrhythmogenic LA LVAs with a standard approach consisting of empiric LA linear ablation. Methods: Patients (pts) with symptomatic paroxysmal or persistent AF were randomized to standard (group 1) or personalized (group 2) SM. Circumferential PV isolation was the primary step in both groups. In group 1, pre-defined linear lesions were applied at the LA roof and bottom, respectively, and at the mitral isthmus only in pts with persistent AF. In group 2, targets for SM (i.e. LVAs) were identified by detailed bipolar voltage mapping (BVM) during sinus rhythm irrespective of AF type. Peak-to-peak electrogram amplitudes were defined as “normal” (&gt; 0.5 mV), as “low voltages” (0.2 to 0.5 mV), or as “scar” (&lt; 0.2 mV). LVAs were targeted by tissue homogenization and / or strategic linear lesions. The primary endpoint was freedom from any atrial arrhythmia (i.e. AF, atrial flutter, or atrial tachycardia) &gt; 30 seconds off antiarrhythmic drugs on serial 7-d-Holter ECG recordings after a follow-up period of 12 months. Results: In total, 124 ablation-naïve pts (mean age 63 ± 9 years, 62 % male, 49 % with persistent AF) were enrolled in this study. LVAs were present in 18 % of pts with paroxysmal and in 41 % of pts with persistent AF (p&lt;0.05). At the end of the follow-up period, 25 out of 59 pts (42 %) in the conventional group were free from arrhythmia recurrence as compared to 40 out of 59 pts (68 %) in the BVM-guided group (unadjusted log rank p = 0.003). Conclusion: Personalized SM guided by endocardial BVM is associated with a higher success rate compared to a conventional approach applying empirical SM based on AF phenotype.
Platelet-Derived 12-Hydroxyeicosatetraenoic Acid Plays an Important Role in Mediating Canine Coronary Thrombosis by Regulating Platelet Glycoprotein IIb/IIIa Activation
Authors: AtsushiKatoh, HisaoIkeda, ToyoakiMurohara, NobuyaHaramaki, HidekiIto, TsutomuImaizumi
Journal: Circulation (1998)

Background—In the thrombotic process of acute coronary syndromes, the pathophysiological role of thromboxane A2 via cyclooxygenase is well established; however, the role of 12-HETE via 12-lipoxygenase is little known. Therefore, we used OPC-29030, a novel specific inhibitor of 12-HETE synthesis, to test whether platelet-derived 12-HETE is involved in mediating cyclic flow variations (CFVs) and platelet aggregation in stenosed and endothelium-injured canine coronary arteries. Methods and Results—After developing CFVs, dogs received a vehicle or OPC-29030 intravenously. Plasma and intraplatelet 12-HETE levels increased after CFVs. OPC-29030 but not vehicle reduced CFVs, which was associated with decreases in plasma and intraplatelet 12-HETE levels. Cessation of OPC-29030 restored CFVs in association with increases in plasma and intraplatelet 12-HETE levels. ADP and U46619 induced ex vivo platelet 12-HETE production and aggregation. After OPC-29030 administration, the ADP- and U46619-induced increases in ex ...
Abstract 5712: Identification of a highly suppressive Treg subset associated with immunotherapy response
Authors: Teresa Troiani, Simona Romano, Paolo D'Arrigo, Anna Rea, Martina Tufano, Emilio F. Giunta, Giuseppe Matarrese, Claudio Procaccini, Nunzia Novizio, Vincenza Vigorito, Deriggio Faicchia, Giuseppe Argenziano, Fortunato Ciardiello, Maria F. Romano
Journal: Cancer Research (2018)

Abstract Melanoma often exploits Treg to avoid immune attack. Treg is a heterogeneous population with respect to immunosuppressive capability. Lymphocytes are particularly rich in FKBP51 (encoded by FKBP5 gene), known as the receptor for FK506. Melanoma aberrantly expresses this protein, which sustains resistance and invasion. Melanoma/immune cell interaction, through PD-L1/PD1, bidirectionally generates FKBP5 splicing inducing a lower molecular weight form termed FKBP51s. In 64 advanced melanoma patient PBMCs, we found that FKBP51s marked a Treg subset that correlated to anti-CTLA4 response. More precisely, a Treg FKBP51s+ count &amp;lt;1% was associated with unresponsiveness (normal donor-range 0.1-0.7%). Aim of the present study was to assess the role of Treg FKBP51s+ as potential biomarker of response in a different cohort of patients treated with anti-PD1. In addition, the suppressive potential of Treg FKBP51s+ in comparison with that of Treg FKBP51s- is investigated. To date, we have outcomes of 11 patients. For each patient, we have collected up to 10 blood samples, at T0 and before each treatment, to monitor Tregs. In 5 responder patients, Treg FKBP51s+ was &amp;gt;1.2 and &amp;lt;4.8; in 5 non responder patients, the count was &amp;gt;0.04 and &amp;lt;0.8 After a transient increase following the first administration, the count decreased to 0.3+0.2% in responder patients. Interestingly, a patient with count =0.7% developed autoimmune side effects that led to therapy discontinuation. Resolution of side effects was accompanied by a value increase to 9.9%; anti-PD1 re-administration was then successful. In vitro iTreg generation showed that FKBP51s was upregulated in Treg CD25high, Ki67high and p70S6khigh, corresponding to a highly metabolically active profile with strong suppressive capability. In conclusion, melanoma patients that benefit from immune checkpoint targeted therapy are recognizable by an expansion of a Treg subset which is marked by FKBP51s, a splicing protein isoform generated by triggering of surface antigens (PD-L1, PD1), abundantly expressed on highly suppressive Tregs. Citation Format: Teresa Troiani, Simona Romano, Paolo D'Arrigo, Anna Rea, Martina Tufano, Emilio F. Giunta, Giuseppe Matarrese, Claudio Procaccini, Nunzia Novizio, Vincenza Vigorito, Deriggio Faicchia, Giuseppe Argenziano, Fortunato Ciardiello, Maria F. Romano. Identification of a highly suppressive Treg subset associated with immunotherapy response [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 5712.
Abstract 5183: Using transposon elements to elucidate the genetic mechanisms of HCC-associated lung metastases
Authors: Lilian H. Lo, Amy P. Chiu, Xiao-Xiao Li, Barbara R. Tschida, Dewi K. Rowlands, David A. Largaespada, Vincent W. Keng
Journal: Cancer Research (2018)

Abstract Metastases account for most cancer-related deaths as a result of primary cancer spreading to distant sites. Amongst human hepatocellular carcinoma (HCC), there is a drastic decrease in the survival rate observed in patients with early stage localized HCC to late stage metastasis-associated HCC. Importantly, the genetic mechanisms associated with metastasis-associated HCC remains elusive. Therefore, a forward genetic screen in mice using Sleeping Beauty (SB) insertional mutagenesis system was developed to identify genes associated with metastasis-associated HCC. Truncated version of the epidermal growth factor receptor (Egfr) gene was frequently detected in both mouse primary liver tumors and lung metastases, which was confirmed by DNA sequencing and RNA sequencing. This indicates the importance of Egfr mutations for liver tumorigenesis and the metastasis process. More importantly, additional candidate genes involved in the metastasis process were also identified by our forward genetic screen and showed to be relevant in human HCC patients at the M1 cancer metastasis stage. Taken together, our study shows that the SB screen yields a high fraction of relevant events in human liver cancer and can provide valuable information on the evolution of metastasis-associated HCC. The authors declare that they have no competing interests. Citation Format: Lilian H. Lo, Amy P. Chiu, Xiao-Xiao Li, Barbara R. Tschida, Dewi K. Rowlands, David A. Largaespada, Vincent W. Keng. Using transposon elements to elucidate the genetic mechanisms of HCC-associated lung metastases [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 5183.
Abstract 5032: Tumor in a Dish (TiD): Novel approach for precision therapy using patient-derived cells
Authors: Prabhu Ramamoorthy, Sufi Thomas, Sathish Ramalingam, Gaurav Fnu, Sita G. Sittampalam, Roy A. Jensen, Shrikant Anant
Journal: Cancer Research (2018)

Abstract Metastatic colorectal cancer is a major cause of cancer-related deaths. Most patients with metastatic disease fail to respond to current chemotherapeutic agents. Current, traditional culture model is not appropriate to study the metastatic disease in in vitro condition. Hence, there is an ominous need for developing new therapeutic and preventive agents that can target metastatic cancer. Unfortunately, there are no good in vitro as well as in vivo models available for studying metastatic disease. Hence, in this abstract, we demonstrate the development of a new lung model system, called Primitive Lung in a Dish or PLiD with cancer cells called “Tumor in a Dish” or TiD. The PLiD system shows expression of specific cell type marker like E-cadherin (epithelial cell) vimentin (fibroblast), CD31 (heme-endothelial cells) and LYVE1 (lymph-endothelial cells). Interestingly, we showed expression of lung functional protein like surfactant protein B and D. In the multicell type TiD system, cancer cells were grown in a 3-dimensional (3D) PLiD system containing normal epithelial cells, fibroblasts and endothelial cells. The model resembles in vivo tumor microenvironments, including cell-cell contact, tumor architecture, and the influence of different cell types. We next determined the efficacy of standard colon cancer chemotherapeutic agents. We observed differential activity of 5FU in TiD system when compared to standard 2D and single-cell type 3D cultures. Another surprising result we found was with freshly isolated colon cancer cells from patient samples. Without knowing the genetic characteristics of the cancer tissue, the TiD system was able to identify cells that were resistant to oxaliplatin. Moreover, using this method, we have developed novel drugs that target cancer cells while not affecting the normal tissue. More importantly, the technique has significant utility in precision/personalized medicine, wherein this phenotypic screen can be coupled with current DNA pharmacogenetics to identify the ideal therapeutic agent, thereby increasing the probability of response to treatment while reducing unnecessary side effects. Citation Format: Prabhu Ramamoorthy, Sufi Thomas, Sathish Ramalingam, Gaurav Fnu, Sita G. Sittampalam, Roy A. Jensen, Shrikant Anant. Tumor in a Dish (TiD): Novel approach for precision therapy using patient-derived cells [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 5032.
Cardioprotective Effect of Diazoxide Is Mediated by Activation of Sarcolemmal but Not Mitochondrial ATP-Sensitive Potassium Channels in Mice
Authors: MasashiSuzuki, TomoakiSaito, ToshiakiSato, MasajiTamagawa, TakashiMiki, SusumuSeino, HaruakiNakaya
Journal: Circulation (2003)

Background— We recently demonstrated that the sarcolemmal ATP-sensitive potassium (sarcKATP) channel plays a key role in cardioprotection against ischemia/reperfusion injuries in Kir6.2-knockout (KO) mice. In the present study, we evaluated the effects of diazoxide, a mitochondrial ATP-sensitive potassium (mitoKATP) channel opener, on ischemia-induced myocardial stunning in sarcKATP channel-deficient mice. Methods and Results— Langendorff-perfused hearts of wild-type (WT) and KO mice were subjected to global ischemia/reperfusion. Diazoxide improved the recovery of contractile function in WT hearts but not in KO hearts. Treatment with HMR1098 (a sarcKATP channel blocker) but not 5-hydroxydecanoate (a mitoKATP channel blocker) abolished the cardioprotective effect of diazoxide in WT hearts. In coronary-perfused WT ventricular muscle preparations, action potential shortening during ischemia was accelerated in the presence of diazoxide. Conclusions— Diazoxide enhances action potential shortening during ischem...
The Effect of an Ordinary Meal on the Electrocardiogram. Normal Standards in Middle-Aged Men and Women
Authors: Ernstsimonson, Ancelkeys
Journal: Circulation (1950)

In previous studies on young men it was found that definite changes in the electrocardiogram are produced by an ordinary meal. This work has been extended with a larger series of older men and women. In general, the results confirm the previous studies but an age trend was found in some items. The combined material allowed an analysis of the correlations between the changes in the various items of measurement and more detailed consideration of the physiologic mechanisms involved. Normal fiducial limits for the changes induced by a meal were calculated to provide a basis of discrimination between normal and abnormal responses.
Abstract 3493: Promoting role of AKR1B10 in HER2+ breast cancer at early stage
Authors: Ramina Khoshaba, Deliang Cao
Journal: Cancer Research (2018)

Abstract Background: Breast cancer is the second most common cause of female cancer-related death in the United States. Aldo-keto reductase 1B10 (AKR1B10) is a 35-kDa protein that is highly expressed in breast cancer in infiltrative and Ductal Carcinoma in Situ (DCIS) stages. Human epidermal growth factor receptor2 (HER2) is a tyrosine kinase receptor which is highly expressed in 15-20% of infiltrative breast cancer but over 60-70 % in DCIS. Methods: We targeted AKR1B10 and HER2 expression using AKR1B10 and HER2 expression lentiviruses in a panel of breast cancer cell lines that have different endogenous expression status of AKR1B10 or HER2, including MCF-7(AKR1B10-/HER2 low), ZR-75-1(AKR1B10-/HER2+), MDA-MB-468 (AKR1B10+/HER2-) and the normal human mammary cells MCF10A (AKR1B10-/HER2-). We investigated the effects of AKR1B10 or HER2 expression on cell proliferation, clonogenicity, adhesion, migration, and invasion. Western blots were performed to check integrin α5, δ-catenin expression and the phosphorylation of signaling proteins in Raf/MEK/ERK and AKT/P-mTOR pathways. Results: Our data showed that AKR1B10 promoted the proliferation of HER2+ human breast cancer cell. The results of colony forming and soft agar assays demonstrated that AKR1B10 stimulated clonogenic efficiency of HER2+ cells. Also, AKR1B10 promoted HER2+ cells adhesion to extracellular matrix, facilitated their migration and significantly increased their invasion capability. Moreover, it upregulated integrin α5, δ-catenin expression, and promoted HER2+ cells growth and invasiveness through the activation of AKT/mTOR and Raf/MEK/ERK pathways Conclusion: AKR1B10 promotes HER2+ human breast cancer cell proliferation and invasiveness. Citation Format: Ramina Khoshaba, Deliang Cao. Promoting role of AKR1B10 in HER2+ breast cancer at early stage [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 3493.
Abstract 2394: Racial disparity in bladder cancer and identification of altered metabolism in African American compared to European American bladder cancer
Authors: Venkata Rao Vantaku, Sri Ramya Donepudi, Tiffany Dorsey, Vasanta Putluri, Chandrashekar Ambati, Tang Wei, Michael M. Ittmann, Martha K. Terris, Seth Lerner, Stefan Ambs, Yair Lotan, Arun Sreekumar, Nagireddy Putluri
Journal: Cancer Research (2018)

Abstract This abstract has been withheld from publication due to its inclusion in the AACR Annual Meeting 2018 Official Press Program. It will be posted online following its presentation. Citation Format: Venkata Rao Vantaku, Sri Ramya Donepudi, Tiffany Dorsey, Vasanta Putluri, Chandrashekar Ambati, Tang Wei, Michael M. Ittmann, Martha K. Terris, Seth Lerner, Stefan Ambs, Yair Lotan, Arun Sreekumar, Nagireddy Putluri. Racial disparity in bladder cancer and identification of altered metabolism in African American compared to European American bladder 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 2394.
Denis Anthony Mitchison
Authors: Amina Jindani
Journal: BMJ (2018)

It is with great sadness that I report the death of Professor Denis Anthony Mitchison CMG, with whom I had the privilege of working for several decades.

Denis Anthony Mitchison was born in Oxford on 6 September 1919 to a family of scientific and scholarly distinction: he was the son of the Labour politician Dick Mitchison and his wife, Naomi (nee Haldane), a novelist and poet. His uncle was the biologist J B S Haldane and his grandfather the physiologist John Scott Haldane.

Educated at the Dragon School, Oxford, and Abbotsholme School, Mitchison went on to Trinity College, Cambridge, where he studied natural sciences and obtained a first class degree and a senior scholarship. He then changed to medicine, qualifying from University College in 1943.

Throughout his academic life, Mitchison had a major role in the treatment of …
Coagulation Factor Xa Induces Endothelium-Dependent Relaxations in Rat Aorta
Authors: PaulSchaeffer, Anne-MarieMares, FrédériqueDol, FrançoiseBono, Jean-MarcHerbert
Journal: Circulation Research (1997)

Abstract The relaxing effect of coagulation factor Xa on phenylephrine-contracted rat aortic rings was compared with the effect of thrombin and trypsin. All three proteases induced a dose-dependent relaxation in the presence of an intact endothelium. EC50 values were 3±1, 24±9, and 16±1 nmol/L for thrombin, trypsin, and factor Xa, respectively. Whereas thrombin induced rapid relaxations followed by partial recontraction, trypsin and factor Xa induced slower sustained effects. Factor Xa–induced relaxations were not affected by hirudin at high concentrations (1 μmol/L) but were abolished by DX9065A, a specific inhibitor of the catalytic activity of factor Xa. Furthermore, no relaxations to factor Xa could be elicited in the presence of the NO synthase inhibitor Nω-nitro-l-arginine methyl ester (100 μmol/L), whereas relaxations were not altered in the presence of the inactive enantiomer Nω-nitro-d-arginine methyl ester (100 μmol/L). Addition of factor Xa together with thrombin induced relaxations that were l...