tbuckley/cabot-search huggingface dataset:
Differentiation of Bone Marrow Stromal Cells Into the Cardiac Phenotype Requires Intercellular Communication With Myocytes
Authors: MeifengXu, MaqsoodWani, Yan-ShanDai, JiangWang, MeiYan, AhmarAyub, MuhammadAshraf
Journal: Circulation (2004)

Background— Bone marrow stromal cells (BMSCs) have the potential to differentiate into various cells and can transdifferentiate into myocytes if an appropriate cellular environment is provided. However, the molecular signals that underlie this process are not fully understood. In this study, we show that BMSC differentiation is dependent on communication with cells in their microenvironment. Methods and Results— BMSCs were isolated from green fluorescent protein (GFP)–transgenic mice and cocultured with myocytes in a ratio of 1:40. Myocytes were obtained from neonatal rat ventricles. The differentiation of BMSCs in coculture was confirmed by immunohistochemistry, electron microscopy, and reverse transcription–polymerase chain reaction. Before coculturing, the BMSCs were negative for α-actinin and exhibited a nucleus with many nucleoli. After 7-day coculture with myocytes, some BMSCs became α-actinin–positive and formed gap junctions with native myocytes. However, BMSCs separated from myocytes by a semiper...
Role of Vascular Cell Adhesion Molecule-1 and Fibronectin Connecting Segment-1 in Monocyte Rolling and Adhesion on Early Atherosclerotic Lesions
Authors: YuqingHuo, AliHafezi-Moghadam, KlausLey
Journal: Circulation Research (2000)

Abstract—Atherosclerotic lesion development seems to be inflammatory in nature and involves the recruitment of monocytes to the vessel wall. In this study, we investigated the role of vascular cell adhesion molecule-1 (VCAM-1) and fibronectin (FN) connecting segment-1 containing the amino acid sequence ILDV as functional ligands for α4β1 integrin (VLA-4) in monocyte rolling and adherence to early atherosclerotic lesions. Carotid arteries of apolipoprotein E–deficient mice were isolated and perfused with monocytes or U937 cells. Cell adhesion was reduced 95±4% by monoclonal antibodies HP1/2 and HP2/1, which block VLA-4 binding to both VCAM-1 and FN connecting segment-1. mAb HP1/3 preferentially blocked interaction of VLA-4 with FN but not VCAM-1 and decreased adhesion by 30±8%. In contrast, blocking VCAM-1 by perfusing the isolated carotid artery with mAb MK-2.7 reduced adhesion by 75±12%. Mononuclear cell adhesion to the early atherosclerotic endothelium was inhibited by 68±10% in the presence of EILDVPST...
Renal Function After Catheter Ablation of Atrial Fibrillation
Authors: YoshihideTakahashi, AtsushiTakahashi, TaishiKuwahara, KenjiOkubo, TadashiFujino, KatsumasaTakagi, EmikoNakashima, TetsuoKamiishi, HiroyukiHikita, KenzoHirao, MitsuakiIsobe
Journal: Circulation (2011)

Background—Kidney function is a known predictor of cardiovascular morbidity and mortality. Although patients with atrial fibrillation (AF) often have kidney dysfunction, less is known about the association between AF and kidney function. We sought to assess changes in kidney function after catheter ablation of AF. Methods and Results—Patients who underwent catheter ablation of AF were recruited for the present prospective study. Estimated glomerular filtration rate (eGFR) was evaluated before and 1 year after the ablation. Three hundred eighty-six patients (paroxysmal AF, 135; persistent AF, 106; longstanding persistent AF, 145) were studied. Their baseline eGFR was 68±14 mL · min−1 · 1.73 m−2. Sixty-six percent and 26% of patients had eGFR of 60 to 89 and 30 to 59 mL · min−1 · 1.73 m−2, respectively. Overall, 278 patients (72%) were arrhythmia free over a 1-year follow-up. In patients free from arrhythmia, eGFR increased 3 months later and was maintained until 1 year, whereas in patients with recurrences...
Nonmuscle and Smooth Muscle Myosin Heavy Chain Expression in Rejected Cardiac Allografts
Authors: Jun-ichiSuzuki, MitsuakiIsobe, MasanoriAikawa, MotohiroKawauchi, IchiroShiojima, NaotoKobayashi, AkihiroTojo, ToruSuzuki, KenjiroKimura, ToshioNishikawa, TatsuoSakai, MorieSekiguchi, YoshioYazaki, RyozoNagai
Journal: Circulation (1996)

Background Diagnosis of acute rejection and graft arteriosclerosis (chronic rejection) is critical to the success of cardiac transplantation, but accurate diagnosis is often difficult. We have reported that there are three types of vascular myosin heavy chain (MHC) isoforms: SM1, SM2, and SMemb. SM2 is specifically expressed in differentiated smooth muscle cells (SMCs). SMemb is a nonmuscle-type MHC abundantly expressed in SMCs of fetal aorta. Methods and Results To evaluate the usefulness of MHC expression for diagnosis and analysis of acute and chronic rejection, heterotopic cardiac transplantation was performed in rats and monkeys. Immunohistochemistry, electron microscopy, and Northern blot assay were performed to evaluate MHC expression. SMemb was expressed in spindle-shaped cells located in acutely rejected myocardium in the rats and monkeys. These cells were also observed in areas lacking cellular infiltration. These SMemb-positive cells were activated fibroblasts or myofibroblasts. SMemb mRNA was ...
Targeting Platelets in Acute Experimental Stroke
Authors: ChristophKleinschnitz, MiroslavaPozgajova, MirkoPham, MartinBendszus, BernhardNieswandt, GuidoStoll
Journal: Circulation (2007)

Background— Ischemic stroke is a frequent and serious disease with limited treatment options. Platelets can adhere to hypoxic cerebral endothelial cells by binding of their glycoprotein (GP) Ib receptor to von Willebrand factor. Exposure of subendothelial matrix proteins further facilitates firm attachment of platelets to the vessel wall by binding of collagen to their GPVI receptor. In the present study, we addressed the pathogenic role of GPIb, GPVI, and the aggregation receptor GPIIb/IIIa in experimental stroke in mice. Methods and Results— Complete blockade of GPIbα was achieved by intravenous injection of 100 μg Fab fragments of the monoclonal antibody p0p/B to mice undergoing 1 hour of transient middle cerebral artery occlusion. At 24 hours after transient middle cerebral artery occlusion, cerebral infarct volumes were assessed by 2,3,5-triphenyltetrazolium chloride staining. In mice treated with anti-GPIbα Fab 1 hour before middle cerebral artery occlusion, ischemic lesions were reduced to ≈40% com...
Abstract 14749: Extra-cardiac Mitral Valve Repair - Experience With the Adjustable BACE Device
Authors: Jaishankar Raman, Thomas Beaver, Krishna Talluri
Journal: Circulation (2015)

Introduction: Functional mitral regurgitation (MR) is primarily due to abnormalities of the ventricular muscle in the presence of normal mitral leaflets. Present surgical treatment, repair or replacement, address the mitral valve annulus and leaflets, not the ventricular muscle. We describe our early and mid-term clinical experience with extra-cardiac treatment of MR with a novel, device that is implanted on a beating heart and can be adjusted remotely. Hypothesis: Evaluation of efficacy and outcomes Methods: Between Dec, 2008 and June, 2015, thirty one patients (mean age 59 years) with functional and ischemic MR were evaluated at 9 multi-national centers. All patients had severe MR (Mean MR grade 3.1) on trans-thoracic and/or trans-esophageal echocardiography, and impaired LV function (Mean EF 33.6%). Risk assessment by Logistic Euroscore was16.58%. Patients underwent implantation of a custom made BACE (Basal Annuloplasty of the Cardia Externally) device, along with CABG (mean 2.5 grafts per patient). The device was placed at the base of the heart, overlapping the atrial and ventricular surfaces of the atrio-ventricular groove circumferentially. All procedures were performed on a beating heart with the majority of them performed off-pump. Intra-operative trans-esophageal echocardiography allowed customized inflation of specific chambers to selectively deform the annulus and sub-annular myocardium. Two patients required delayed peri-operative adjustment of the BACE device. Results: The degree of MR improved from a mean of 3.1 to 0.9. This &gt;2 class improvement in MR was sustained over the 12 month follow up period in all patients. Moderately severe TR in 3 patients went down to trivial. There was one peri-operative death associated with balloon related leg ischemia. One device was explanted early at re-exploration for bleeding. There were no device related complications. Conclusions: Ischemic functional mitral valve regurgitation can be treated by epicardial implantation and dynamic adjustment of the BACE device. This technique has significant implications in the treatment of ischemic functional MR without entering the heart, with the added ability to remotely adjust the device.
Abstract 5809: Synergistic effect of alectinib and everolimus on anaplastic large cell lymphoma cells via ALK-mTOR pathway inhibition
Authors: Dongchan Kim, Hyejoo Park, Youngil Koh, Sung-Soo Yoon
Journal: Cancer Research (2018)

Abstract Purpose Anaplastic lymphoma kinase (ALK) fusion is associated with various kinds of cancer, including anaplastic large cell lymphoma (ALCL). We investigated the efficacy of combination between ALK inhibitor and mammalian target of rapamycin (mTOR) inhibitor in ALK-positive ALCL cells. Methods &amp; Results ALK-positive cancer cell lines were treated with ALK and/or mTOR inhibitors and assessed for cell viability. Treatment of ALK-positive ALCL cell lines with the combination resulted in a synergistic effect in Karpas299 cells but not in SU-DHL-1 cells. Viability of Karpas299 cell was reduced to 26.4% (p&amp;lt;0.001) by alectinib-everolimus combination treatment compared to the single treatment groups (alectinib: 59.5%, everolimus: 51.6%); the Combination Index (CI) value of 0.316 indicated a synergistic effect of the combination treatment. Moreover, changes in intracellular signaling were analyzed by western blot. Combination treatment augmented increase of ALK-mTOR de-phosphorylation, and cleavage of poly ADP ribose polymerase (PARP) molecules. Combination treatment significantly increased the numbers of Karpas299 cells in subG1 (p = 0.0096 everolimus), and G0/G1 (p = 0.0018 alectinib; 0.0013 everolimus) cell cycle arrest compared to single treatment groups. We investigated the biological differences between Karpas299 and SU-DHL-1 cell lines using RNA sequencing data obtained from Sequence Read Archive (SRA). The RNA expression pattern of the ALK isoforms ALK-201 and 203 was different between the two cell lines. These data indicated that the relatively high expression of ALK-203 in SU-DHL1 cells could explain the lack of synergism in response to the combination treatment observed. Conclusions Combination treatment with alectinib and everolimus synergistically reduced cell survival, augmented inhibition of cellular signaling, and increased cell cycle arrest in Karpas299 but not in SU-DHL1 cells. These differences might be attributable to differential expression of ALK isoforms between the two cell lines. Citation Format: Dongchan Kim, Hyejoo Park, Youngil Koh, Sung-Soo Yoon. Synergistic effect of alectinib and everolimus on anaplastic large cell lymphoma cells via ALK-mTOR pathway inhibition [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 5809.
Intratumoral G100, a TLR4 Agonist, Induces Antitumor Immune Responses and Tumor Regression in Patients with Merkel Cell Carcinoma
Authors: Shailender Bhatia, Natalie J. Miller, Hailing Lu, Natalie V. Longino, Dafina Ibrani, Michi M. Shinohara, David R. Byrd, Upendra Parvathaneni, Rima Kulikauskas, Jan ter Meulen, Frank J. Hsu, David M. Koelle, Paul Nghiem
Journal: Clinical Cancer Research (2018)

G100 is a toll-like receptor 4 (TLR4) agonist that triggers innate and adaptive antitumor immune responses in preclinical models. This pilot study assessed the safety, efficacy, and immunologic activity of intratumoral (IT) administration of G100 in patients with Merkel cell carcinoma (MCC).
Maternal adiposity in pregnancy and offspring asthma in adulthood
Authors: Anna P. Westberg, Minna K. Salonen, Mikaela von Bonsdorff, Clive Osmond, Eero Kajantie, Johan G. Eriksson
Journal: European Respiratory Journal (2018)

Adverse pre- and neonatal conditions, such as low birth weight and parental smoking, have, in recent years, been found to increase the risk of developing asthma [1, 2]. The underlying mechanisms behind this appear to include an altered epigenetic programming of the developing fetal airways and immune system [3, 4]. High maternal body mass index in pregnancy is associated with an increased prevalence of offspring asthma in men in adult life <http://ow.ly/cOWh30kWpBU>
Abstract 1381: Targeting histone acetyltransferases to reprogram high C-MYC expressing cancers
Authors: Elodie M. Da Costa, Gregory Armaos, Annie Beaudry, Chantal Richer, Maxime Caron, Pascal St-Onge, Jeffrey Johnson, Nevan Krogan, Yuka Sai, Michael Downey, Daniel Sinnett, Serge McGraw, Noël J. Raynal
Journal: Cancer Research (2018)

Abstract In cancer, epigenetic modifications are strongly altered and are responsible for gene expression aberrations. In a drug screening initiative, we recently reported that proscillaridin, a cardiac glycoside (CG), exhibits unsuspected epigenetic and anticancer activities. To understand CG's epigenetic mechanisms of action, we performed RNA sequencing analysis, which showed proscillaridin effects on global gene expressions in acute lymphoblastic leukemia cells (MOLT-4). Genes associated with apoptosis and cell differentiation were upregulated whereas master transcription factors and oncogenic pathway genes were downregulated. Mechanistic studies revealed that proscillaridin decreased histone 3 acetylation, which correlated with histone acetyltransferase (KATs) downregulation (CBP, P300, TIP60, GCN5 and MOZ). Acetylome studies by mass spectrometry showed an acetylation loss in chromatin regulators, the oncogene C-MYC and its associated proteins. Proscillaridin induced C-MYC transcript and protein degradation. Moreover, in a panel of cancer cell lines, we measured that cancer cells sensitivity to proscillaridin treatment was positively correlated with C-MYC protein levels. Conversely, proscillaridin did not affect C-MYC protein level in low C-MYC expressing cancer cell lines. For the first time, we showed that CGs target histone acetyltransferases and C-MYC oncogene in high C-MYC expressing cancers. We propose that CGs can be repurposed as new epigenetic drugs in high C-MYC expressing cancers. Citation Format: Elodie M. Da Costa, Gregory Armaos, Annie Beaudry, Chantal Richer, Maxime Caron, Pascal St-Onge, Jeffrey Johnson, Nevan Krogan, Yuka Sai, Michael Downey, Daniel Sinnett, Serge McGraw, Noël J. Raynal. Targeting histone acetyltransferases to reprogram high C-MYC expressing cancers [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 1381.
Characteristics of Immune Response to Tumor‐Associated Antigens and Immune Cell Profile in Patients With Hepatocellular Carcinoma
Authors: Yuki Inada, Eishiro Mizukoshi, Takuya Seike, Toshikatsu Tamai, Noriho Iida, Masaaki Kitahara, Tatsuya Yamashita, Kuniaki Arai, Takeshi Terashima, Kazumi Fushimi, Taro Yamashita, Masao Honda, Shuichi Kaneko
Journal: Hepatology (2018)

Host antitumor immune responses may be different between hepatocellular carcinoma (HCC) caused by metabolic disorders and HCC associated with hepatitis virus infection. In this study, we examined the immune response of tumor‐associated antigen (TAA)–specific T cells and immune cell profile in patients with HCC separated by cause. Thirty‐two patients with hepatitis B virus (HBV)–related HCC, 42 patients with hepatitis C virus–related HCC, and 18 patients with nonalcoholic steatohepatitis (NASH)–related HCC were analyzed. The frequencies of TAA‐specific T cells, the expression levels of surface markers on each immune cell, and the expression of each TAA in HCC tissue were measured. The immune response to TAA and immune cell profile were markedly different among the three groups. The immune response to TAA in the NASH‐related HCC group was weaker than the responses in the other two groups. In patients with NASH‐related HCC, the frequencies of effector regulatory T cells (eTregs) and cluster of differentiation 8–positive (CD8 + ) T cells strongly expressing cytotoxic T‐lymphocyte antigen (CTLA)‐4 were high. The frequency of CD8 + T cells strongly expressing programmed cell death 1 was the highest in patients with HBV‐related HCC. Among these immune cell profiles, the frequencies of C‐X‐C motif chemokine receptor 3 + eTregs and CTLA‐4 + CD8 + T cells were inversely correlated with the strength of the TAA‐specific T‐cell immune response, and the restoration of TAA‐specific T‐cell responses by anti‐CTLA‐4 antibody was observed. Conclusion : The immune response to TAA were markedly different among the three groups, and a correlation with the immune cell profile was observed, suggesting that development of immunotherapy based on the etiology of HCC may lead to more effective treatment outcomes.
Amisulpride and olanzapine followed by open-label treatment with clozapine in first-episode schizophrenia and schizophreniform disorder (OPTiMiSE): a three-phase switching study
Authors: René S Kahn, Inge Winter van Rossum, Stefan Leucht, Philip McGuire, Shon W Lewis, Marion Leboyer, Celso Arango, Paola Dazzan, Richard Drake, Stephan Heres, Covadonga M Díaz-Caneja, Dan Rujescu, Mark Weiser, Silvana Galderisi, Birte Glenthøj, Marinus J C Eijkemans, W Wolfgang Fleischhacker, Shitij Kapur, Iris E Sommer, René S Kahn, Iris E Sommer, Inge Winter-van Rossum, Metten Somers, Paula C Ywema, Shitisj Kapur, Philip McGuire, Marion Leboyer, Andreas Meyer-Lindenberg, Shon W Lewis, Stefan Leucht, Celso Arango, Wolfgang W Fleischhacker, Anne Lotte Meijering, Jocelyn Petter, Resy Van de Brug, Joost Schotsman, Jildou Zwerver, Jos Peuskens, Marc De Hert, Erik Thys, Lucho G Hranov, Valentin Hranov, Jan Libiger, Richard Köhler, Pavel Mohr, Birte Glenthoj, Brian Broberg, Signe Düring, Lone Baandrup, Stephane Jamain, Stephan Heres, Dan Rujescu, Ina Giegling, Mark Weiser, Mor Bar Heim, Michael Davidson, Silvana Galderisi, Paola Bucci, Armida Mucci, Janusz Rybakowski, Agnieszka Remlinger-Molenda, Ilan Gonen, Paull Radu, Marina Díaz-Marsá, Alberto Rodriguez, Tomas Palomo, Roberto Rodriguez-Jimenez, Paz García-Portilla, Miquel Bernardo, Julio Bobes, Christina Vilares Oliveira, Gregor Berger, Claudia Wildt, Paola Dazzan, Roccio Perez-Iglesias, Richard Drake, Sarah Gregory, Danielle Wilson, Covadonga M Díaz-Caneja, Marinus J C Eijkemans
Journal: The Lancet Psychiatry (2018)
Chronic Intravascular Hemolysis after Aortic Valve Replacement
Authors: Elaineeyster, Johnrothchild, Olgamychajliw
Journal: Circulation (1971)

To assess the severity of hemolysis and to determine whether severity of hemolysis was related to type of prosthesis, hematocrit readings (Hct), schistocyte counts (S), reticulocyte counts (R), and determinations of haptoglobin (Hp), lactic acid dehydrogenase (LDH), bilirubin, urinary hemoglobin, and urinary hemosiderin (Hs) were performed on 54 patients who had three different types of aortic ball-valve prostheses. Hemolysis, as determined by absence of haptoglobins or hemosiderinuria or R>3.5% in the absence of bleeding, was detected in 39 of the 54 patients (72%). S, R, LDH, and bilirubin were higher in patients without haptoglobins than in those with haptoglobins (P  10 per 1,000 cells, R>5%, and LDH>500 mU was observed only with Starr-Edwards valves (16 of the 34 pat...
Abstract 863: Targeted α-therapy for treatment of metastatic melanoma
Authors: Jessie Nedrow, Greg McCarty, Angel Cortez, Sanchita Roy, George Sgouros
Journal: Cancer Research (2018)

Abstract Background Very late antigen 4 (VLA-4; also called integrin α4β1) is overexpressed in melanoma tumors with an active role in tumor growth, angiogenesis, and metastasis. This makes VLA-4 an ideal antigenic target for targeted alpha therapy. The expression of VLA-4 on primary melanomas in human correlates with the development of metastasis and has been associated with high risk of metastasis and tumor progression. Furthermore, up-regulation of VLA-4 in melanoma is associated with a more aggressive, metastatic phenotype. Here in we evaluated an 225Ac-anti-VLA-4 conjugate as well as its 111In-labeled companion imaging agent for targeted radiotherapy in an aggressive mouse melanoma model. Methods An anti-VLA-4 antibody was conjugated to DOTA for 225Ac-labeling and DTPA for 111In-labeling. The resulting agents, 225Ac- or 111In-labeled anti-VLA-4 were evaluated in vitro, including binding affinity, internalization, and clonogenic assays. Furthermore, the therapeutic efficacy of 225Ac-anti-VLA-4 will be evaluated in multiple metastatic animal models of melanoma. Results 111In-DTPA-anti-VLA-4 demonstrated high affinity for VLA-4 in B16F10 cells, having a Kd of 0.18 ± 0.05 nM and approximately 46% was internalized at 6 hours. For delivery of an α-emitting radionuclide to VLA-4 positive tumor cells, the DOTA conjugate was labeled with 225Ac with specific activity of 3.5 MBq/nmol and &amp;gt;95% radiochemical purity, and demonstrated selective uptake in VLA-4 positive B16F10 cells. Clonogenic assays demonstrated a decrease in the surviving fraction of B16F10 cells treated with 225Ac-DOTA-anti-VLA-4 compared to controls. Therapeutic efficacy studies are currently underway. Conclusion 111In- and 225Ac-labeled anti-VLA-4 antibody conjugates are capable of selectively delivering radionuclides for SPECT imaging and targeted alpha therapy to melanoma tumor cells that overexpresses VLA-4. The agents presented here have the potential to identify and treat patients who have metastatic melanoma. Citation Format: Jessie Nedrow, Greg McCarty, Angel Cortez, Sanchita Roy, George Sgouros. Targeted α-therapy for treatment of metastatic melanoma [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 863.
Abstract 5210: Liver prometastatic genes in patients with and without colorectal cancer
Authors: Fernando Vidal-Vanaclocha
Journal: Cancer Research (2018)

Abstract Metastasis-related hepatic genes were investigated in the tumor-unaffected hepatic tissue from patients with hepatic colorectal cancer (CRC) metastases. In addition, the contribution of CRC and patient's clinical parameters and comorbidities to hepatic expression of CRC prometastatic genes was also studied in new hepatic biopsies from metastasis-free CRC patients and from CRC-free patients used as controls. The expression level of 58% metastasis-associated hepatic genes significantly changed between patients with and without CRC. Principal component and Linear discriminant statistical analyses, and a hierarchical cluster analysis based on Pearson's correlation indices uncovered a subset of 37 CRC-dependent liver prometastatic genes able to segregate patients with and without CRC. Functionally, they belonged to immune regulation, inflammation, metabolic bioprotection, hepatokines and regeneration factors. More importantly, a multivariate canonical correlation analysis showed the additional contribution of patient's pathophysiology and comorbidities to hepatic gene expression and metastasis risk. The liver prometastatic gene expression pattern represented a patient-specific and heterogeneous hepatic reaction to CRC-specific factors, which developed prior to metastatic recurrence and varied according to location of such CRC in the left and right-sided colonic area and rectum. Citation Format: Fernando Vidal-Vanaclocha. Liver prometastatic genes in patients with and without colorectal 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 5210.