tbuckley/cabot-search huggingface dataset:
SP0202 Functional autoantibodies against vascular receptors in systemic sclerosis
Authors: G. Riemekasten
Journal: Annals of the Rheumatic Diseases (2013)

Simultaneously occurring functional autoantibodies directed to angiotensin II type 1 receptor (AT<sub>1</sub>R) and endothelin-1 type A receptor (ET<sub>A</sub>R) are present in the majority of patients with systemic sclerosis (SSc). The levels of the antibodies correlate with each other suggesting a strong link of these antibodies in SSc. Presence of high anti-AT<sub>1</sub>R/ET<sub>A</sub>R Ab levels in sera of SSc patients reveal a 10-fold increased risk for development of lung fibrosis. In addition, there is a strong association of the antibodies with pulmonary arterial hypertension and other SSc features. Chronic stimulation of AT1R and ETAR may lead to several clinical symptoms found in SSc. Therefore, we hypothesize a causal role of the antibodies in disease pathogenesis of systemic sclerosis. AT1R and ETAR are present on endothelial cells, smooth muscle cells, fibroblasts, and immune cells. Therefore, in vitro as well as in vivo experiments are preformed to proof our concept. At present, we use affinity-purified IgG from SSc patients and block all effects by the receptor blockers to proof the specificity of the observed effects. On endothelial cells, anti-AT1R- and anti-ETAR induce TGFβ, endothelial cell proliferation, but also reduced endothelial cell viability. They affect endothelial cell-mediated wound healing and induce adhesion molecules and several proinflammatory and profibrotic cytokines, especially IL-8, a strong chemo attractant for neutrophils. Antibody-mediated modulation of endothelial cell function increased migration of neutrophils in vitro and in vivo. In fibroblast, the antibodies induce collagen-I expression. Moreover, the antibodies have an impact on the innate immune system and via IL-8 and CCL18 activation, on the inflammatory process present in SSc. More convincing data come from in vivo studies: Adoptive transfer of the antibodies induce neutrophilic alveolitis in mice. Therefore, there is a growing body of evidence showing a direct link between the presence of the antibodies and SSc pathogenesis. The simultaneous stimulation of AT1R and ETAR by these antibodies was blocked best by simultaneous blockade of the AT1R and ETAR-mediated pathways. Blockade of only one pathway may lead to receptor activation through the other pathway that would explain missing effects of single ETAR blockade on lung fibrosis. Combined blockade of both receptor pathways could be, therefore, of advantage in SSc patients. Unfortunately, the antibodies are very resistant to immunosuppressants including autologeous stem cell transplantation. Taken together, anti-AT1R and -ETAR antibody-mediated pathology seem to contribute to SSc pathogenesis and can explain several clinical features found in SSc. Addressing the antibodies and their effects my provide novel therapeutic targets in SSc. <h3>Disclosure of Interest</h3> G. Riemekasten Consultant for: CellTrend GmbH Luckenwalde and Actelion, Pfizer
The Threshold for Prophylactic Platelet Transfusions in Adults with Acute Myeloid Leukemia
Authors: Paolo Rebulla, Guido Finazzi, Francesca Marangoni, Giuseppe Avvisati, Luigi Gugliotta, Gianni Tognoni, Tiziano Barbui, Franco Mandelli, Girolamo Sirchia
Journal: New England Journal of Medicine (1997)

Prophylactic platelet transfusions are usually administered to patients receiving myelotoxic chemotherapy when their platelet count falls below 20,000 per cubic millimeter. Some observations suggest that lower platelet counts can be appropriate in patients in stable condition, but the safety of lower thresholds is uncertain.
LB-004 Balance Of Roles For Distinct Cd1d-reactive ‘nkt’ Cell Populations In Th1-type Anti-viral And Th2 Pro-fibrotic Responses In Viral Hepatitis
Authors: M Exley
Journal: Gut (2014)

<h3>Introduction</h3> NKT can enhance anti-pathogen and anti-tumour immunity via NK and DC, leading to T/B cell activation. Th1-biassed NKT can contribute to protective responses against cancer and viruses. However, NKT can contribute to immunopathology in chronic infections. Patient NKT defects are reversible <i>in vitro</i>, so we are investigating correcting such defects in models and clinic. NKT are required for optimal resistance to certain viruses. Mice lacking all NKT are impaired in lymphocyte activation and in picornavirus clearance. Conversely to acute infection, chronic viral stimulation of NKT can lead to immunopathology. CD1d-specific γδ T cells respond to CD1d induced by infection, causing viral myocarditis. <h3>Methods</h3> Model liver and human hepatic immune responses were measured. CD1d reactivity of distinct T cell populations was assayed, compared to total T cell responses. <h3>Results</h3> NKT also potentially contribute to chronic Hepatitis C, since human liver-specific γδ Vδ3 T cells were CD1d-reactive. CD1d is up-regulated by HCV and high level hepatic CD1d-reactive NKT produce pro-inflammatory Th1 cytokines in chronic hepatitis C and their Type 2 responses increase in cirrhosis. <h3>Conclusion</h3> NKT in Chronic Hepatitis C, instead of being protective, may promote inflammation and fibrosis while suppressing anti-tumour responses: their inhibition might have clinical utility. <h3>Disclosure of Interest</h3> M. Exley Shareholder of: NKT Therapeutics, Inc.
Abstract 5293: Mixed micelles of triblock copolymers enhance delivery of indocyanine green for fluorescent tumor imaging
Authors: Christopher Mount, Tae Hee Kim, Benjamin Dulken, Xingde Li, Wayne Gombotz, Suzie Pun
Journal: Cancer Research (2011)

Abstract The goal of this study is to develop formulations for non-invasive, near-infrared detection of tumors. Indocyanine green (ICG) is an FDA-approved near-infrared (NIR) imaging agent that is clinically used for angiography and evaluation of liver function. ICG could potentially be used as a NIR fluorescence imaging agent for shallow tumors such as breast cancers. To fulfill this potential, formulations that improve the stability of ICG and direct its accumulation in tumors are necessary. We have previously described Pluronic F127 copolymer micelles that stabilize ICG, enhance its stability, and facilitate tumor accumulation in vivo after systemic administration. A major advantage of Pluronic F127 is its temperature-sensitive behavior that results in more stable micelle formulations at body temperature. However, Pluronic F127 micelles are not stable at room temperature, making micelle preparation and handling challenging. We hypothesized that mixed micelles formed from both Pluronic F127 and a temperature insensitive triblock copolymer composed of poly(ethylene oxide) and poly(3-hydroxybutyrate) (PEO-PHB-PEO), would result in micelles that are both easy to formulate at room temperature and that demonstrate increased stability at body temperature. Micelle formulations with various ratios of Pluronic F127: PEO-PHB-PEO were prepared and loaded with ICG. The micelle stability was determined by assessment of critical micelle concentration measurements, and time-course fluorescence assays were conducted to assess the ability of each micelle formulation to stabilize ICG fluorescence in buffer conditions. The ICG-loaded micelles were administered to tumor-bearing mice by tail vein injection and tumor localization was monitored by non-invasive fluorescence imaging in live mice. The polymer ratio used in micelle formulation was found to play a significant role in the ability of each preparation to stabilize ICG fluorescence Mixed micelles were found to enhance the stability of ICG fluorescence in buffer conditions, and CMC was shown to be dependent on polymer ratios. In vivo, mixed micelles were found to be more effective at maintaining ICG fluorescence in the bloodstream and achieved higher fluorescence signals in the tumor tissues compared with either PEO-PHB-PEO or Pluronic 127 micelles. These results suggest that the mixed micelle formulations offer a promising route to stabilizing these nanoparticles for improved delivery of NIR fluorescent contrast agents to tumors for imaging applications. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 5293. doi:10.1158/1538-7445.AM2011-5293
P92 NEWLY ESTABLISHED MURINE HEPATIC ANGIOSARCOMA CELL LINES: IN VITRO AND IN VIVO MODEL TO STUDY ANGIOSARCOMA BIOLOGY AND TARGETED THERAPIES
Authors: S. Rothweiler, M. Dill, L. Terracciano, Z. Makowska, L. Quagliata, M. Heim, D. Semela
Journal: Journal of Hepatology (2014)
Relative Effectiveness of Ferroglycine Sulfate and Ferrous Sulfate
Authors: Ernest Beutler, Susanne E. Larsh
Journal: New England Journal of Medicine (1962)

IN recent years the drug industry has presented the practicing physician with an ever increasing array of iron preparations. Medical representatives, armed with excerpts from the medical literature, urge him that each new iron preparation is better tolerated and more efficacious than any of the others. One of us (E.B.) has recently reviewed the literature on which these claims are based, and found the lack of any convincing evidence that any preparation was superior, in either tolerance or efficacy, to ferrous sulfate.1 However, the lack of such evidence does not mean that there may not be iron preparations that are . . .
A2.15 Ra phenotype at presentation differs among patients with few versus many autoantibodies
Authors: VFAM Derksen, S Ajeganova, AHM van der Helm-van Mil, I Hafström, TWJ Huizinga, REM Toes, LA Trouw, B Svensson, D van der Woude
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background and objectives</h3> Patients with rheumatoid arthritis (RA) are frequently positive for one or several autoantibodies like rheumatoid factor (RF), anti-citrullinated protein antibodies (ACPA) and anti-carbamylated protein antibodies (Anti-CarP). The number of autoantibodies can be seen as a proxy for the breadth of the (humoral) autoimmune response. Seropositive and seronegative patients differ in respect to underlying risk factors and disease outcome. However, it is unclear whether seropositive and seronegative patients differ at presentation, and if disease presentation is affected by the number of autoantibodies present. Therefore, this study investigated this association. <h3>Materials and methods</h3> Two independent cohorts of early RA patients were analysed: Leiden Early Arthritis Cohort (EAC) (n = 845), and the Swedish BARFOT (Better Anti-rheumatic Farmaco-therapy) study (n = 805). All patients fulfilled the 1987 ACR criteria and had a short symptom duration (EAC &lt; 24 months, BARFOT &lt; 12 months). Autoantibody status was determined at baseline. Commercial agglutination tests were used to measure RF in BARFOT. Commercial enzyme linked immunosorbent assays (ELISAs) were used to measure RF in EAC and anti-CCP2 in both cohorts. Antibodies against carbamylated fetal calf serum were measured for both cohorts in Leiden using in-house ELISAs. Ordinal regression investigating the association between baseline characteristics and the number of autoantibodies was performed to calculate odds ratios (ORs) and 95% confidence intervals (CI). To study independent associations, variables with a univariate p &lt; 0.10 were included in a multivariate model. <h3>Results</h3> The distribution of the number of autoantibodies in both cohorts was similar (EAC (0:31%, 1:17%, 2:17%, 3:35%) and BARFOT (0:33%, 1:14%, 2:24%, 3:29%)). In multivariate analysis in both cohorts, patients with more RA-associated antibodies were younger (OR(95% CI) per 10 years: EAC 0.89(0.80–0.98), BARFOT 0.87(0.79–0.95)), more often smokers (OR(95% CI): EAC 1.61(1.19–2.16), BARFOT 1.59(1.20–2.11)), had a longer symptom duration (OR(95% CI) per 3 months: EAC 1.11(1.01–1.22), BARFOT 1.25(1.09–1.43)) and a higher ESR (OR(95% CI) per 10 mm/hour: EAC 1.11 (1.05–1.18), BARFOT 1.20(1.12–1.30)) at presentation compared to patients with fewer autoantibodies. <h3>Conclusions</h3> The number of autoantibodies is associates with differences in several phenotypic characteristics at presentation, indicating that the breadth of the (humoral) autoimmune response affects the initial clinical presentation of RA.
Abstract 4940: Prognostic significance of Fbw7 in human melanoma and its role in cell migration.
Authors: Yabin Cheng
Journal: Cancer Research (2013)

Abstract The E3 ubiquitin ligase Fbw7 (F-box and WD repeat domain-containing 7) is broadly considered as a tumor suppressor because of its role in turnover of several well-known onco-proteins. However, the role of Fbw7 in melanomagenesis is not clear. To investigate the expression profile and biological functions of Fbw7 in melanoma, we examined Fbw7 expression level using melanoma tissue microarray and immunohistochemistry. Our data showed that Fbw7 expression is significantly reduced in primary melanoma compared with dysplastic nevi (P = 0.020) and further reduced in metastatic melanoma compared with primary melanoma (P = 0.011). Furthermore, we observed a strong correlation between negative Fbw7 expression and a worse 5-year survival of melanoma patients (P = 0.015). We also found that both Fbw7 protein and mRNA expression was significantly reduced in 9 melanoma cell lines compared with normal melanocytes. Moreover, our in vitro studies showed a remarkable increase of cell migration and stress fibre formation in Fbw7 knockdown cells, and treatment of selective MEK inhibitor abrogated Fbw7α knockdown induced melanoma cell migration. Taken together, our findings indicate that Fbw7 plays an important role in melanoma progression, and Fbw7 inhibits melanoma cell migration through MAPK-ERK signalling pathway and may serve as a prognostic marker. Citation Format: Yabin Cheng. Prognostic significance of Fbw7 in human melanoma and its role in cell migration. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4940. doi:10.1158/1538-7445.AM2013-4940
Metastatic Embryonal Carcinoma of the Testis Associated with Elevated Plasma TSH-like Activity and Hyperthyroidism
Authors: Neal H. Steigbigel, Joost J. Oppenheim, Lawrence M. Fishman, Paul P. Carbone
Journal: New England Journal of Medicine (1964)

EVIDENCE has been adduced in recent years for the association of a variety of neoplastic states with the elaboration of polypeptide or protein substances having hormonal action. The majority of such syndromes have involved tissues not usually considered to be endocrine in function. The endocrinologically active substances produced have resulted in hyperadrenocorticism1 2 3 on the basis of excess ACTH-like material in patients with carcinomas of the lung and several other neoplasms; erythrocytosis4 caused by the elaboration of erythropoietic substances in relation to cerebellar hemangioblastoma, various tumors of the kidney and liver and uter ne fibroids; hypoglycemia, possibly related to increased insulin-like . . .
Abstract B08: eIF4E3 forms a novel cap-binding complex for mRNA translation initiation.
Authors: Ari L. Landon, Parameswary A Muniandy, Simone Houng, Amol Shetty, Kevin Becker, Katherine Borden, Ronald B. Gartenhaus
Journal: Clinical Cancer Research (2015)

Abstract Dysregulation of mRNA translation can alter the cellular phenotype leading to cancer initiation, maintenance, progression, invasion or metastasis. Cap-dependent translation is the primary mechanism of mRNA translation in eukaryotic cells. The conventional cap-binding complex, eIF4F consists of three components including eIF4A, eIF4G and eIF4E1. eIF4E1 binds the 7-methyl-guanosine-cap (cap) structure in the mRNA and functions to bridge mRNA to the ribosome. eIF4E3 is another member of the eIF4E family that has been recently shown to bind cap using biophysical approach. We explored the biological function of eIF4E3 in a diffuse large B-cell lymphoma model. We found that in the absence or lack of eIF4E1 phosphorylation, eIF4E3 expression is enhanced, and this increases the cap-binding ability of eIF4E3. We find that eIF4E3 also physically associates with the components of the cap-binding complex eIF4A and eIF4G, essentially forming a novel cap-binding complex. We interrogated the functional capacity of the eIF4E3-mediated translation by analyzing the translatome and transcriptome of eIF4E3 expressing cells. eIF4E3 and eIF4E1 mutually regulate a high fraction of total mRNA transcripts, while exclusively modulating translation of select messages. Interestingly, we identified selective motif enrichments in the 5'UTR that may facilitate transcript selection by eIF4E1 or eIF4E3. Together, we have identified a novel cap-binding complex consisting of eIF4A, eIF4G and eIF4E3, which can initiate mRNA translation of select messages. Citation Format: Ari L. Landon, Parameswary A Muniandy, Simone Houng, Amol Shetty, Kevin Becker, Katherine Borden, Ronald B. Gartenhaus. eIF4E3 forms a novel cap-binding complex for mRNA translation initiation. [abstract]. In: Proceedings of the AACR Special Conference on Hematologic Malignancies: Translating Discoveries to Novel Therapies; Sep 20-23, 2014; Philadelphia, PA. Philadelphia (PA): AACR; Clin Cancer Res 2015;21(17 Suppl):Abstract nr B08.
2014 AHA/ACC Guideline for the Management of Patients With Non–ST-Elevation Acute Coronary Syndromes: Executive Summary
Authors: Ezra A. Amsterdam, Nanette K. Wenger, Ralph G. Brindis, Donald E. Casey, Theodore G. Ganiats, David R. Holmes, Allan S. Jaffe, Hani Jneid, Rosemary F. Kelly, Michael C. Kontos, Glenn N. Levine, Philip R. Liebson, Debabrata Mukherjee, Eric D. Peterson, Marc S. Sabatine, Richard W. Smalling, Susan J. Zieman
Journal: Journal of the American College of Cardiology (2014)
A New Echocardiographic Parameter of Arterial Stiffness in End-Stage Renal Disease
Authors: Musa Şahin, Hakkı Şimşek, Aytaç Akyol, Serkan Akdağ, Mehmet Yaman, Bekir İnan, Cemalettin Aydın, Şeref Kul, Yasemin Soyoral, Hasan Ali Gümrükçüoğlu
Journal: Journal of the American College of Cardiology (2013)
Abstract 2827: <i>In vivo</i> effects of ICA-1 on breast cancer and glioma xenografts
Authors: Mildred E. Acevedo-Duncan
Journal: Cancer Research (2012)

Abstract High grade breast cancer and gliomas are highly lethal tumors for which novel therapies are necessary. PKC-iota (PKC-α), an atypical protein kinase C isoform confers resistance to drug-induced apoptosis in cancer cells (J. Biol. Chem. 272; 44: 27521-27524). This research focuses on the in-vivo effects of the novel PKC-α inhibitor [1H-imidazole-4-carboxamide, 5-amino-1-[2,3-dihydroxy-4-[(phosphonooxy) methyl] cyclopentyl]-[1R-(1α, 2α, 3 β, 4 α)] (ICA-1; The Inter. J. Biochem. &amp; Cell Biol. 43:784-794) on breast cancer and glioma xenografts. ICA-1 targets a unique sequence (amino acid residues 469-475) in the catalytic domain of PKC-α. The breast cancer xenograft study evaluated 12 athymic nude mice while the glioma xenograft study was comprised of 6 female athymic nude mice. The breast cancer xenografts were divided into saline control (n= 4) and xenografts injected with ICA-1 (20mg/kg; 5 μM; every other day, n = 8). The six glioma nude mice were divided into two groups consisting of saline controls (n = 3) and xenografts injected with ICA-1(80 mg/kg; 20 μM; every other day) when the tumor reached 100 mm3 on day 5 post implantation (n = 3). MDA-MB-468 breast cancer cells were injected subcutaneously (2 x106 cells/ flank in 0.2 ml PBS) while the human glioblastoma cell line U-87 MG was also injected into different mice subcutaneously in the right flank (1x106 cells/flank in 0.1 ml PBS). Tumor volume was calculated using formula: length x width x width x ½. Results showed that ICA-1 prevented glioma tumor growth even after stopping dosing at day 9 and continuing to monitor tumor growth for an additional nine days. Glioma tumor volume in these ICA-1 treated mice decreased by 51% compared to controls. ICA-1 was also effective in decreasing breast cancer xenograft growth by 50%. The weight of either ICA-1 treated breast cancer or glioma xenograft mice did not decrease compared to controls. These results indicate that ICA-1 is effective in preventing the growth of breast cancer and glioma xenografts. Future studies will establish toxicity data and optimize the dose and frequency of ICA-1 treatment for potential anti-PKC-α therapy. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2827. doi:1538-7445.AM2012-2827
TCTAP A-094 Effect of Beta-blocker Therapy on Mortality Rates in Stable Coronary Artery Disease Patients with Normal Left Ventricular Function After Percutaneous Coronary Intervention.
Authors: Seung-Jung Park, Se Hun Kang, Min Su Kim, Hee-soon Park, Byeong Joo Bae, Sang Soo Cheon, Jae Hyung Roh, Pil Hyung Lee, Mineok Chang, Hyun Woo Park, Sung Han Yoon, Jung-Min Ahn, Duk-Woo Park, Soo-Jin Kang, Seung-Whan Lee, Young-Hak Kim, Cheol Whan Lee, Seong-Wook Park
Journal: Journal of the American College of Cardiology (2015)
Somatostatin Receptor Scintigraphy and Somatostatin Therapy in the Evaluation and Treatment of Malignant Thymoma
Authors: KE LIN, &NA; D. NGUYEN, DAVID S. ETTINGER, BENNETT B. CHIN
Journal: Clinical Nuclear Medicine (1999)

Purpose: This report illustrates the potential diagnostic and therapeutic utility of somatostatin receptor scintigraphy and therapy with somatostatin. Methods: In-111 pentetreotide (In-11 octreotide), a somatostatin analog, was used to define the receptor status and the extent of disease in a case of malignant thymoma. Results: Subsequent treatment with nonradioactive somatostatin inhibited tumor growth. Conclusion: In-111 octreotide may be usfeul to define tumor receptor status and may provide prognostic information useful in determining subsequent therapy.