tbuckley/cabot-search huggingface dataset:
Effects of phospholipid scramblase 1 (PLSCR1) on migration and invasion of ovarian cancer cells
Authors: Fiona Simpkins, Beihua Dong, Saubhik Sengupta, Yan Xu, Peter J. Sims, Robert H. Silverman
Journal: Cancer Research (2006)

3525   PSCR1 is an endofacial membrane protein identified by its capacity to promote transbilayer phospholipid movement in response to Ca 2+ . Recent evidence suggests that PLSCR1 also participates in cell response to growth factors and cytokines, influencing myeloid differentiation, the anti-viral activity of interferon and tumor growth. PLSCR1 is induced by growth factor EGF, which has been shown to stimulate ovarian cancer cell proliferation and invasion. Previously, we showed that tumors overexpressing (OE) PLSCR1 in the human ovarian carcinoma cell line (HEY 1B) were smaller and had increased infiltration of leukocytes and macrophages. Based on these prior results, we hypothesized that PLSCR1 would also affect the migratory or invasive properties of the ovarian cancer cells themselves. Human PLSCR1 cDNA was stably expressed and siRNAs were transiently transfected into HEY 1B. Immunoblots confirmed OE and downregulation of PLSCR1. Cell migration and invasion were determined using collagen I and matrigel coated Boyden chambers, respectively. Quantitation of cell migration and invasion was performed by colorometry per manufacturer’s protocol (Chemicon Inc) and utilizing ImagePro(v 5.1), respectively. To validate invasion results, zymogram assays for matrix metalloproteases (MMPs) were performed. To determine expression of PLSCR1, immunoblots were probed using PLSCR1 monoclonal antibody. The PLSCR1 transfected cells had a 3-fold increase in PLSCR1 compared to the parental, untransfected cells. Transient siRNA treatment of HEY 1B resulted in about a 5-fold decrease in PLSCR1. Downregulation of PLSCR1 with siRNA decreased cell migration by 40% compared to untreated cells (p=0.03) or by 70% compared to control siRNA treated cells (p=0.15). However, migration was similar when comparing the OE-PLSCR1 and parental cell lines. Remarkably, invasion was significantly increased (3-fold) in the OE-PLSCR1 cells when compared to parental HEY 1B (p=0.008). Accordingly, invasion of the PLSCR1 siRNA treated cells was decreased 2-fold compared with the siRNA control (p=0.038). MMP-9 activity was increased 2- to 3-fold in the OE-PLSCR1 cells when compared to parental, untransfected HEY 1B and decreased 2-3 fold in the PLSRC1 siRNA treated cells when compared to parental HEY 1B and the siRNA control . These data suggest that PLSCR1 promotes invasion in ovarian cancer cells  in vitro . In future studies, we plan to evaluate the effect of PLSCR1 on the invasion properties of human ovarian cancer cells implanted orthotopically in athymic mice. PLSCR1 is a potential molecular target for ovarian cancer therapy.
Co-Activation of AMPK and mTORC1 Is Synthetically Lethal in Acute Myeloid Leukemia
Authors: Pierre Sujobert, Etienne Paubelle, Adrien Grenier, Florence Zylbersztejn, Mireille Lambert, Laury Poulain, Elizabeth Townsend, Jean-Marie Brusq, Edwige Nicodeme, Justine Decrooqc, Ina Nepstad, Alexa Green, Marie-Anne Hospital, Nathalie Jacque, Olivier Hermine, Marc Foretz, Benoit Viollet, Catherine Lacombe, David M. Weinstock, Patrick Mayeux, Ivan C Moura, Didier Bouscary, Jerome Tamburini
Journal: Blood (2014)
Abstract 16917: Enodcardial Scar Size Predicts Adverse Outcomes Following Radiofrequency Catheter Ablation in Patients with Recurrent Ventricular Tachycardia
Authors: Matthew Peters, Ameer Abutaleb, Jing Tian, Ghada Ahmad, Alejandro Jimenez, Anastasio Saliaris, Vincent See, Stephen Shorofsky, Timm Dickfeld
Journal: Circulation (2011)

Introduction: Sustained Ventricular Tachycardia (VT) often occurs in the setting of structural heart disease and myocardial scar. Little is known about the prognostic value of endocardial scar or border zone after VT ablation. Methods 48 consecutive ICD patients with structural heart disease and documented VT underwent detailed endocardial voltage mapping (&gt; 200 LV points). Endocardial scar and border zone were defined as &lt; 0.5mV and 0.5-1.5 mV, respectively. Scar burden was defined as the ratio between endocardial scar and total left ventricular (LV) endocardial area, scar + border zone burden as the ratio between scar plus border area divided by LV area. Follow-up was included if ICD clinic notes or interrogations could be obtained at &lt; 6 month intervals. VT recurrence (VTR) was defined as any VT &gt;30s or causing appropriate ICD shocks. Mortality was determined using the Social Security Database. Results: All patients (46 male, age 62+12.18; 81% CAD; EF 26.39+12.47) underwent clinically indicated VT ablation with a mean follow-up of 31.5±8.7 months. A scar burden of &gt;10% was associated with a higher rate of first VT recurrence (VTR) with 1.9, 1.5,and 1.2 fold increases seen at 12, 24 and 36 moths, respectively. Similarly, a scar+border zone burden of &gt;25% resulted in 2.0, 1.6 and 1.2 fold increases of VTR at 12, 24 and 36 months, respectively. A scar burden of &gt;10%was also associated with a 4.0, 3.7 and 3.9 fold increase in mortality at 12, 24 and 36 months, respectively. Similarly, a scar+border zone burden of &gt;25% was associated with a 6.0, 3.8 and 3.8 fold increase in mortality at 12, 24 and 36 months, respectively. Conclusions: Large myocardial scar/border zone substrate correlates with earlier recurrence of VT and higher long-term mortality after VT ablation. This finding may allow for more refined risk stratification and guide an individualized pharmacologic/ablation-based approach to VT.
An Open-Label, Phase 2, Multicenter Study Of The Safety Of Long-Term Treatment With Siltuximab (an Anti-Interleukin-6 Monoclonal Antibody) In Patients With Multicentric Castleman’s Disease
Authors: Frits Van Rhee, Corey Casper, Peter M Voorhees, Luis E Fayad, Helgi van de Velde, Jessica Vermeulen, Xiang Qin, Ming Qi, Brenda Tromp, Razelle Kurzrock
Journal: Blood (2013)
Abstract 87: Cyclosporin A does not Prevent Myocardial Dysfunction after Resuscitation from Cardiac Arrest in Rats
Authors: Iyad M Ayoub, Jeejabai Radhakrishnan, Raúl J Gazmuri
Journal: Circulation (2007)

Objective: We have previously reported in a rat model of VF and closed-chest resuscitation that cytochrome c is released into the bloodstream after resuscitation from cardiac arrest attaining plasma levels inversely proportional to survival. Recent evidence indicates that release of cytochrome c during ischemia and reperfusion may be a manifestation of prolonged opening of the mitochondrial permeability transition pore (mPTP). In this study, we investigated whether cyclosporin A (CsA, an inhibitor of mPTP opening) can prevent post-resuscitation (PR) myocardial dysfunction and improve survival. Methods: VF was electrically induced and left untreated for 10 mins. Resuscitation was attempted by 8 mins of chest compression followed by biphasic waveform defibrillation. Rats were randomized to received a bolus CsA (10 mg/kg) five minutes before inducing VF (n=6), immediately before starting chest compression (n=6), or to receive vehicle control before inducing VF (n=3) or before starting chest compression (n=3). CsA-treated (n=12) and vehicle-treated (n=6) rats were pooled for this analysis after noticing no differences between subgroups. Resuscitated rats were monitored for up to 6 hours. Results: All rats were successfully resuscitated. Treatment with CsA did not improve PR myocardial function (Table ). Survival time was comparable between CsA-treated (321±67 mins) and vehicle-treated (331±67 mins) rats. Conclusions: In our rat model of VF and resuscitation, CsA failed to prevent PR myocardial dysfunction and improve survival. These data contrast with numerous studies demonstrating a protective effect in isolated heart models of ischemia and reperfusion. Two possible explanations are the mPTP does not open in this unique setting of cardiac arrest and resuscitation, and the optimal in vivo dose of CsA needs to be determined as the protective effects of CsA are dose dependent. Hemodynamic and Left Ventricular Function
A phase I study of IMC-11F8, a fully human anti-epidermal growth factor receptor (EGFR) IgG1 monoclonal antibody in patients with solid tumors. Interim results
Authors: B. Kuenen, E. Witteveen, R. Ruijter, A. Ervin-Haynes, M. Tjin-A-ton, F. Fox, C. Ding, G. Giaccone, E. E. Voest
Journal: Journal of Clinical Oncology (2006)

3024 Background: This ongoing phase I study is being conducted to determine the safety profile and recommended dose of IMC-11F8, a fully-human IgG1 monoclonal antibody that targets the EGFR. Methods: Patients (pts) with advanced solid tumors who are refractory to or have no available standard therapy are eligible to receive IMC-11F8 intravenously either weekly or every other week for 6 weeks (1 cycle). The initial cohort of patients will receive 100 mg of IMC-11F8. In the absence of a dose-limiting toxicity (DLT), dose escalation will be 200, 400, 600, 800, and 1000 mg in successive cohorts. Prior to the initial cycle, pts receive one IMC-11F8 infusion at their assigned cohort followed by a 2-week pharmacokinetic (PK) period. Pts with stable disease or better after cycle 1 are eligible to receive additional cycles of IMC-11F8. Results: 31 of 40 pts have been enrolled in the 100-, 200-, 400-, 600-, and 800-mg cohorts. Pt characteristics are M/F 20/11, median age 58 years (37 - 76), median ECOG score 1 (0–2). No DLTs have been observed. Only grade 1/2 skin rashes were reported. The most frequent adverse events were nausea, vomiting, fatigue, and headache. No infusion reactions were observed. 2 pts (1 confirmed) have achieved a PR, 1 pt with melanoma in the 200-mg cohort with 39+ weeks of weekly IMC-11F8 treatment and 1 pt with rectal cancer in the 400-mg cohort with 20+ weeks of IMC-11F8 administered every other week. 5 pts in the 200- to 600-mg cohorts have stable disease and have received from 11+ to 35+ weeks of IMC-11F8 treatment. A noncompartmental analysis of 20 pts demonstrated that IMC-11F8 exhibits nonlinear PK. As IMC-11F8 escalated from 100 to 600 mg, T 1/2 increased from 67 to 84 hrs, C max increased from 30 to 368 μg/mL, AUC inf increased from 1753 to 67295, and CL decreased from 57.0 to 8.9 mL/hr. Conclusions: These interim results indicate that IMC-11F8 is well tolerated in this patient population. Although a maximum tolerated dose has not been established, IMC-11F8 has shown activity at two different dose levels. [Table: see text]
Abstract 15659: A Biomarker Strategy for the Early Diagnosis of Takotsubo Cardiomyopathy
Authors: Ivan Mendoza, Jorge Betancor, Marlow B Hernandez, Craig R Asher, Gian M Novaro
Journal: Circulation (2011)

Background: Takotsubo cardiomyopathy (TCM) is characterized by reversible left ventricular dysfunction in response to an acute emotional or physical stress. Because the clinical presentation of TCM...
Abstract 2493: Design, Synthesis, and Pharmacologic Actions of a Novel Designer Natriuretic Peptide: CU-NP
Authors: Candace Y Lee, John C Burnett
Journal: Circulation (2007)

Introduction: Designer natriuretic peptides (NPs) hold promise for optimizing pharmacologic profiles of native NPs. We recently designed and synthesized a novel NP, named CU-NP, based on the ring s...
Major depression in the elderly: DSM-III criteria and the dexamethasone suppression test as predictors of treatment response
Authors: J E Spar, A La Rue
Journal: American Journal of Psychiatry (1983)

Twenty-seven elderly individuals with DSM-III diagnoses of major depression who demonstrated a nonsuppressor response to the dexamethasone suppression test had higher pretreatment levels of mood disturbance, required higher dosages of antidepressant medication, and had poorer responses to treatment than 17 clinically similar individuals with a suppressor response. However, when data on the outcomes of suppressors and nonsuppressors were combined, over half of the entire group sustained significant improvement, which supports the practical value of DSM-III criteria for depression in the elderly.
Abstract 12413: 5-Lipoxygenase Facilitates Healing after Myocardial Infarction
Authors: Christina Pachel, Nadja Bloemer, Ulrich Hofmann, Peter Nordbeck, Wolfgang Bauer, Anna Podolskaya, Georg Ertl, Johann Bauersachs, Stefan Frantz
Journal: Circulation (2011)

Background: Early healing after myocardial infarction (MI) is characterized by a strong inflammatory reaction. Most leukotrienes are pro-inflammatory and are therefore potential mediators of cardio...
Primary tumour mutant p53 gene protein and epidermal growth factor receptor expression and doxorubicin plus ifosfamide for recurrent breast cancer
Authors: B.M.J. Cantwell, C. Hennessy, A. Sawan, P.J.D.K. Dawes, M. Millward, T.W.J. Lennard
Journal: Annals of Oncology (1992)
Rupture of the aorta due to radiation injury. Report of a case and electron microscopic study
Authors: T. P. Poon
Journal: JAMA (1968)

Necrotizing aortitis with rupture is a rare complication of radiation of mediastinal structure. To our knowledge, this is the first electron microscopic study of radiation changes of the aorta. Collagen fibers were preserved, but there was slit-like irregular fragmentation of elastic fibers. Marcias-Rojas and Castro<sup>1</sup>previously reported five cases of postradiation rupture of the aorta, all associated with mediastinitis. Our patient had an empyema. It is postulated that infection combined with radiation necrosis may have triggered the rupture.
Abstract 5399: Myocardial Contractile Dysfunction is Associated with Fetal Cardiac Bypass in a Sheep Model
Authors: Jodie Y Duffy, R. Scott Baker, Mitali Basu, Casey Reed, Emily A Heeb, Pirooz Eghtesady
Journal: Circulation (2008)

Declining cardiac output and placental dysfunction are the key barriers to successful fetal cardiac bypass for in utero repair of congenital heart defects. Identifying myocardial dysfunction, especially in the RV that is considered the systemic ventricle in fetal life, may be important for success. We hypothesized that fetal cardiac bypass results in myocardial contractile dysfunction that reduces cardiac output and placental perfusion, leading to placental dysfunction and fetal demise. Three fetuses from mid-term pregnant ewes were subjected to 30 min of cardiac bypass and followed for 120 min after bypass. Piezoelectric crystals (Sonometrics, Ontario, CA) were placed on three axes of the fetal heart and pressure catheters (Millar Instruments, Houston, TX) were inserted in the left and right ventricle (RV). Data were analyzed by repeated measures ANOVA with Fisher’s PLSD post hoc analyses. Representative RV pressure-volume loops in the figure showed that preload increased after bypass, indicated by increased end-diastolic volume (mean 4.1±.7 vs. 4.4±1 mL) and pressure (mean 14.3 ±7 vs. 31.3± 3 mmHg, P&lt;.05). RV contractility decreased after bypass: pre-bypass dPdt max (mmHg/sec) - 880±93 vs. 731±102 at 120 min after bypass (P≤.1) and dP/dt min - 798±4 vs. 689±11 (P≤.1). Preload recruitable stroke work (slope of regression line) also decreased from 28.5±7 pre-bypass to 22.1±5 at 120 min post-bypass. Increased RV preload and RV contractile dysfunction are evident after fetal cardiac bypass. Minimizing the associated myocardial dysfunction is important for the success of fetal surgery to repair complex congenital heart defects. This research has received full or partial funding support from the American Heart Association, AHA National Center.
FDG PET/CT Findings of Recurrent Respiratory Papillomatosis With Malignant Degeneration in the Lung
Authors: Ebru Tatci, Atila Gokcek, Ebru Unsal, Filiz Cimen, Funda Demirag, Senem Yazici, Ozlem Ozmen
Journal: Clinical Nuclear Medicine (2015)

Recurrent respiratory papillomatosis is a rare benign disease caused by HPV-6 or HPV-11. The tumors may rarely undergo malignant degeneration. We performed FDG PET/CT in a patient experiencing recurrent respiratory papillomatosis who had pulmonary involvement. Although squamous cell carcinoma was detected in one of the pulmonary masses, squamous metaplasia with dysplasia were detected in the other one. Intensity modulated radiation therapy was performed to treat the malignancy. Second FDG PET/CT was performed 15 months after radiotherapy.
Late luteal phase dysphoric disorder and DSM-III-R
Authors: R L Spitzer, S K Severino, J B Williams, B L Parry
Journal: American Journal of Psychiatry (1989)

Text and diagnostic criteria for a new category, late luteal phase dysphoric disorder, appear in appendix A of DSM-III-R: "Proposed Diagnostic Categories Needing Further Study." The inclusion of this category in the manual was perhaps the most controversial aspect of the revision of DSM-III. In this paper the authors describe the work of the advisory committee that first proposed the category, the rationale for the category's inclusion in the manual, and the many issues that were the focus of heated debates.
Azacitidine in Older Patients with Acute Myeloid Leukemia (AML) and Adverse Karyotype. Subanalisis from the Alma Study
Authors: Jose Falantes, Guillermo Deben, Violeta Martinez Robles, Joan Bargay, Olga Salamero, Carmen Pedro, Santiago Redondo, Ana Garrido, Juan Miguel Bergua, Mar Tormo, Blanca Xicoy, Patricia Font, Tomás José González-López, Fernando Ramos
Journal: Blood (2014)
Abstract 17173: Caloric Restriction Protects Against Aging Cardiomyopathy, But Not Longevity
Authors: Lin Yan, Shumin Gao, David Ho, Hui Ge, Chunbo Wang, Yimin Tian, Dorothy E Vatner, Stephen F Vatner
Journal: Circulation (2011)

Caloric restriction (CR) is the most common model of enhanced longevity. However, this has been questioned in some mouse models. The goal of this study was to determine if CR protected against aging cardiomyopathy and whether this could account for the enhanced longevity of CR. We studied 2 models of CR, both with 40% calorie reduction; one initiated in 2 month old 129 SVJ mice and continued for 24 months, long term (LT) CR; and the other initiated in mice at 20 months of age, when cardiomyopathy was already developing, and continued for 2 months, short term (ST) CR. The older mice at 2 yrs on normal diet (ND) developed aging cardiomyopathy, compared to young ND mice: left ventricular (LV) systolic function, i.e. LV ejection fraction, was depressed (58±4% vs 71±1%, p&lt;0.05). In addition the cardiomyopathy was characterized by increased myocyte apoptosis (0.29±0.04 vs 0.05±0.02 cells/mm 2 , p&lt;0.05) and LV hypertrophy (LVH), as evidenced by increased LV/ tibial length (TL) (5.7±0.4 vs 4.6±0.1, p&lt;0.05), compared to young ND mice. With LT CR, aging cardiomyopathy did not develop; LV ejection fraction (71±1%), myocyte apoptosis (0.14±0.07 cells/mm 2 ), and LV/TL (4.2±0.2) were significantly improved compared to old ND mice. Surprisingly, ST CR induced similar salutary effects as LT CR with preserved LV ejection fraction (74±1%), reduced myocyte apoptosis (0.07±0.02 cells/mm 2 ) and LV/TL (5.0±0.2). There were also significant decreases in α-tublin (48%), β-tublin (67%) and cleaved desmin (43%), with an increase in intact desmin (32%), reflecting altered cytoskeletal proteins, as well as an increase in antioxidants MnSOD (31%) and catalase (51%). Even more surprisingly, neither LT, nor ST CR improved longevity; in fact, more mice died with CR (55%), than with ND (45%) over the 2 year monitoring period. Thus, CR prevents the development of aging induced cardiomyopathy, potentially by correcting aging induced alterations in cardiac cytoskeletal proteins and increased resistance to oxidative stress. Of therapeutic relevance, instituting this intervention even in later life can rapidly correct the cardiomyopathy of aging. Surprisingly, CR does not enhance longevity in this mouse model, despite prevention of aging cardiomyopathy.
Immune Complexes and Disease.
Authors: H G Kunkel
Journal: Annals of Internal Medicine (1972)

trauma than in a minor procedure involving the mucous membranes, such as a tooth extraction or tonsillectomy.Should we give prophylactic treatment to all pa- tients with von Willebrand's disease undergoing surgical operation simply because of the ready availability of highly effective concentrates of the von Willebrand factor?I think not; we must guard against the danger of overemphasizing specific replacement therapy.We must remember that plasma and all its derivatives useful in the treat- ment of this disorder carry the risk of the development of serum hepatitis in the recipient.In earlier days, when treatment was of necessity empirical, our advice to referring surgeons was as follows:(1) Even though the patient has had abnormal surgical bleeding in the past it may very well not happen again, particularly if careful local hemostasis is practiced at the time of operation; (2) the patient must be advised that he has a hereditary hemorrhagic disorder which may cause him to bleed abnormally but he must also be strongly re- assured that the chances of his bleeding more vigorously than can be readily controlled by local measures or transfusion are virtually nil (this re- assurance in itself may have considerable therapeutic benefit for both the surgeon and the patient); and (3) if abnormal bleeding does occur, use local measures to combat it and transfuse only when there is a clear danger to the patient from blood loss, and then use fresh whole blood if possible.This regime proved effective in most patients and much of the counsel is still valid.However, now fresh noncontact plasma or an appropriate plasma derivative containing the von Willebrand factor should be used instead of fresh whole blood when it is obvious that local hemostatic measures will not suffice.
Abstract 1915: Simvastatin Regulates Insulin Signaling in Endothelial Cells via Activation of AMP-Activated Protein Kinase
Authors: Yehoshua C Levine, Thomas Michel
Journal: Circulation (2008)

Statins exert pleiotropic effects upon the cardiovascular system, but the role of statins in modulation of insulin signaling remains incompletely defined. In these studies, we explore the effects of simvastatin on insulin pathways in bovine aortic endothelial cells (BAEC), and propose a novel mechanism linking these pathways that involves AMP-activated protein kinase (AMPK). Treatment of BAEC with 100 nM insulin promotes the rapid phosphorylation of Akt (3.8±0.2-fold increase; n=4; p&lt;0.01), glycogen synthase kinase-3β (GSK3β, 2.7±0.5-fold increase; n=4; p&lt;0.01), as well as that of critical substrates in the mammalian target of rapamycin (mTOR) axis including mTOR (2.8±0.2-fold increase; n=4; p&lt;0.02) and p70S6K (3.2±0.5-fold increase; n=4; p&lt;0.02). However, in cells pretreated with simvastatin (10 μM for 24 hr), these insulin-dependent phosphorylations are significantly attenuated (62±10%, 48±12%, 53±9%, and 58±13% reduction in the phosphorylation of Akt, GSK3β, mTOR, and p70S6K, respectively; p&lt;0.02; n=4). Given our findings on the modulation of these key metabolic enzymes by simvastatin, we explored the effects of insulin and simvastatin on AMPK. We found that insulin promotes a rapid (within minutes) and robust increase in phosphorylation of both AMPK and its substrate acetyl CoA carboxylase (2.5±0.4-fold increase; n=4; p&lt;0.01). Importantly, transfection of BAEC with siRNA targeting AMPK results in enhanced insulin-dependent phosphorylation of Akt (57±9% enhancement compared to cells transfected with control siRNA; n=4; p&lt;0.015), as well as significant increases in phosphorylation of GSK3β, mTOR, and p70S6K (55±12% enhancement; n=4; p&lt;0.02), indicating a key regulatory role for AMPK in insulin-dependent metabolic signaling. Importantly, in cells transfected with AMPK siRNA, simvastatin treatment no longer attenuates insulin signaling to these substrates, suggesting that AMPK is required for the regulation of insulin pathways by statins. Taken together, these results establish that simvastatin modulates critical insulin responses in endothelial cells, and provide new insights into the roles of AMPK in linking insulin- and statin-regulated metabolic signaling pathways in the vascular wall.