tbuckley/cabot-search huggingface dataset:
Abstract 3971: The type III tgf-β receptor mediates bmp signaling in normal and cancerous mammary epithelial cells
Authors: Catherine E. Gatza, Gerard C. Blobe
Journal: Cancer Research (2010)

Abstract BMP signaling has been shown to enhance breast cancer invasion and bone metastasis, while inhibition of BMP signaling abrogates bone metastasis in an in vivo model. The type III TGF-β receptor (TβRIII) is known to mediate BMP signaling and can inhibit migration, invasion, and metastasis in breast cancer, however the role of TβRIII in regulating BMP signaling in breast cancer has not been examined. The MDA-MB-231, MCF7, and mouse 4T1 breast cancer cell lines, which express low levels of TβRIII, are responsive to BMP2 and 4 treatment as demonstrated by increased Smad1/5/8 phosphorylation, cell migration, and invasion. Restoring TβRIII expression in these cell lines or treatment of MDA-MB-231-Neo cells with recombinant soluble TβRIII (sTβRIII) or with conditioned media from MDA-MB-231-RIII cells inhibited BMP2 and BMP4 induced Smad1/5/8 phosphorylation (pSmad1/5/8) and BMP mediated cell migration. MDA-MB-231-RIII cells also exhibited enhanced growth arrest in response to BMP2 compared to MDA-MB-231-Neo cells, mediated through the up-regulation of p21. In reciprocal studies, shRNA-mediated knockdown of TβRIII expression in the normal mammary epithelial cell lines HMEC and MCF10A, abrogated BMP mediated induction of pSmad1/5/8, demonstrating that TβRIII mediates BMP signaling in normal mammary epithelial cells. Additionally, treatment with both recombinant sTβRIII and conditioned media from MDA-MB-231-RIII cells inhibits BMP mediated induction of pSmad1/5/8, suggesting that sTβRIII is able to inhibit BMP signaling in normal mammary epithelial cells by sequestration of ligand. BMP2 treatment induces cell migration in HMEC cells, which was attenuated by knockdown of TβRIII or treatment with sTβRIII. These data demonstrate that TβRIII mediates BMP signaling in normal mammary epithelial cells and breast cancer cell lines, regulating cell migration, invasion, and proliferation. The effects of sTβRIII suggest that the ratio of membrane bound versus soluble TβRIII plays an important role in mediating BMP signaling and cellular effects in normal and cancer mammary epithelial cells. Further work is underway to elucidate the mechanism by which TβRIII regulates BMP signaling in breast cancer in vitro and in vivo. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3971.
Hypermethylation of O6-Methylguanine-Dna Methyltransferase (Mgmt) Promoter As a Prognostic Biomarker for Stage Ii, III and Iv Colorectal Cancers
Authors: Y. Mori, T. Nagasaka, Y. Umeda, R. Shiwaku, R. Inada, N. Nishida, H. Kishimoto, S. Kagawa, H. Tanioka, H. Mishima, T. Fujiwara, A. Goel
Journal: Annals of Oncology (2014)
Abstract P4-06-15: BP1 Upregulates Twist and Induces EMT in Breast Cancer Cells
Authors: B Hwang, J Rheey, SW Fu, PE. Berg
Journal: Cancer Research (2010)

Abstract Background: We have cloned a gene, BP1, which is a member of the homeobox gene family of transcription factors. Our recent studies have shown that BP1 may play a role in breast cancer cell survival, aggressiveness and metastasis. BP1 protein (pBP1) is expressed in 80% of invasive ductal breast tumors, and is associated with estrogen receptor negativity and tumors of African American women, both associated with aggressive tumors. BP1 is also expressed in metastatic tumors, shown by immunostaining of 46 samples of inflammatory breast cancer; all cases were BP1 positive. Nine cases had metastasized, and all nine metastatic lymph nodes were BP1 positive. BP1 positive cells were observed in lymph channels and blood vessels. Here, we demonstrated BP1 induces the epithelial to mesenchymal transition (EMT), resulting in increased migratory ability. EMT, a process by which cancer cells lose their epithelial features and gain mesenchymal markers, enables tumor cells become more invasive, migratory and can lead to metastasis. Twist, a basic helix-loop-helix (bHLH) transcription factor which triggers EMT, is activated by BP1. Materials and Methods: RNA levels of markers of EMT were verified by real-time PCR and their protein levels by Western blotting and, in some cases, by confocal microscopy. Chromatin immunoprecipitation (ChIP) was performed to verify the BP1 binding site on the Twist promoter. A scratch test was used to measure migratory ability. BP1 knockdown by siRNA transfection was also performed. Recombinant BP1 (rpBP1) was produced in E. coli. Results: Increased expression levels of Twist were observed on microarrays after probing with RNA from MCF-7 cell lines overexpressing BP1. We demonstrated that BP1 can upregulate Twist expression in two different breast cancer cell lines, MCF-7 and Hs578T cells, by binding to the Twist promoter. BP1 upregulates mesenchymal marker expression and down-regulates epithelial marker expression, consistent with EMT. BP1 also promotes breast cancer cell migratory ability, shown by the scratch test. In addition, cells grown in medium supplemented with rpBP1 showed increased Twist expression and migration. Experiments evaluating the effects of siBP1 on EMT are underway. Conclusions: BP1 stimulates Twist expression in MCF-7 and HS578T breast cancer cells, resulting in a more mesenchymal cell phenotype. We therefore hypothesize that BP1 induces EMT by upregulating Twist expression, and may result in metastasis. If BP1 is involved in EMT, it may be a good target for therapy. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P4-06-15.
Hyperuricemia, a Concomitant of Congenital Vasopressin-Resistant Diabetes Insipidus in the Adult
Authors: Phillip Gorden, Gary L. Robertson, J. E. Seegmiller
Journal: New England Journal of Medicine (1971)

Abstract Hyperuricemia was found in four adults but was absent in two children with congenital vasopressin-resistant diabetes insipidus. In the two oldest adults gouty arthritis developed at 30 and 42 years of age respectively. On a purine-free diet the 24-hour urinary excretion of urate was normal. Endogenous uric acid clearance was low in all adults, and the ratio of uric acid to creatinine clearance was low in three of four hyperuricemic patients. In the two patients studied, clearance of para-amino hippurate was low, and the filtration fraction elevated. All the adult patients had dilatation of the urinary collecting system. Plasma arginine vasopressin concentrations, measured by radioimmunoassay, were higher than normal for any given period of dehydration but appropriate for the osmolality. Neither water diuresis nor high concentrations of plasma vasopressin were found to affect the renal handling of urate. Hyperuricemia may be a common acquired abnormality in this disease.
P189 Evaluation of the role of cardio-pulmonary exercise testing in the diagnosis of unexplained breathlessness
Authors: J. E. R. Thing, B. Mukherjee, K. Murphy, H. Tighe, L. Howard
Journal: Thorax (2011)

<h3>Introduction and Objectives</h3> Cardio-Pulmonary Exercise Testing (CPET) provides a non-invasive measurement of cardiac and pulmonary function. CPET offers a unique assessment tool for the investigation of patients with unexplained dyspnoea (UD). These individuals often undergo exhaustive, expensive and invasive assessment without definitive diagnosis. CPET can provide valuable diagnostic information and helps to focus further assessment of the dyspnoeic patient. The aim of this retrospective cohort study was to evaluate the outcome of CPET in patients with UD and to determine how clinically useful the test is at influencing further management. <h3>Methods</h3> CPET data were collected between February 2008 and February 2011 for patients with UD and analysed retrospectively. Data included demographics, pre-CPET investigation results, the CPET report and post-CPET clinic letters. This information was accessed via hospital reporting systems as well as a local CPET database and patient notes. <h3>Results</h3> Patient demographics and pre-CPET investigation data are shown in Abstract P189 table 1. Patients were assigned diagnoses based on test reports. A total of 96 (64%) patient letters were obtained to determine whether the test had affected the diagnostic outcome directly, indirectly or not at all. 78 (81%) of the tests resulted in direct outcomes, 12 (13%) resulted in indirect outcomes and 6 (6%) had no impact on further investigation or diagnosis. A significant proportion (27%) of patients undergoing CPET for UD responded normally to exercise and were discharged with reassurance. 15% were diagnosed with dysfunctional breathing and referred to a specialist physiotherapist for breathing retraining. 57 (38%) patients were diagnosed as having an exclusively normal or dysfunctional breathing response to exercise. Of these, many had undergone investigation prior to CPET including 19 ECG, 14 V/Q scans, nine CT scans, six coronary angiograms, four cardiac treadmill tests, two nuclear medicine stress tests and one cardiac MRI. <h3>Conclusions</h3> By introducing CPET at an earlier stage in the diagnostic algorithm for UD, many invasive and expensive investigations could have been avoided. CPET resulted in direct outcomes for 81% of the patients, highlighting the diagnostic importance of CPET in the investigation of UD.
Effect of Aerosolized Recombinant Human DNase on Exacerbations of Respiratory Symptoms and on Pulmonary Function in Patients with Cystic Fibrosis
Authors: Henry J. Fuchs, Drucy S. Borowitz, David H. Christiansen, Edward M. Morris, Martha L. Nash, Bonnie W. Ramsey, Beryl J. Rosenstein, Arnold L. Smith, Mary Ellen Wohl
Journal: New England Journal of Medicine (1994)

Respiratory disease in patients with cystic fibrosis is characterized by airway obstruction caused by the accumulation of thick, purulent secretions, which results in recurrent, symptomatic exacerbations. The viscoelasticity of the secretions can be reduced in vitro by recombinant human deoxyribonuclease I (rhDNase), a bioengineered copy of the human enzyme.
AB1190-HPR Patients' Experiences with Intensive Combination Treatment Strategies for Early Rheumatoid Arthritis: A Longitudinal Qualitative Study Embedded in the Carera Trial
Authors: S. Meyfroidt, K. Van der Elst, D. De Cock, J. Joly, M. Hulscher, R. Westhovens, P. Verschueren
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> The current recommendations for early Rheumatoid Arthritis (eRA) management focus on achieving clinical remission as soon as possible with an early and intensive treatment. Understanding patients9 experiences and ideas regarding their treatment could make healthcare professionals (HPs) more aware of and timely responsive to patients9 preferences, which might result in a better treatment adherence, an improved health status and higher satisfaction with care. <h3>Objectives</h3> To gain a longitudinal understanding of the experiences of patients with eRA with intensive combination treatment strategies (ICTS) at two time points in the early phase of the treatment process. <h3>Methods</h3> We performed a longitudinal, qualitative study embedded in the CareRA (Care in eRA) trial, a multicentre RCT comparing different combinations of conventional DMARDs plus step-down bridging schemes of glucocorticoids for eRA. Patients with eRA participating in the CareRA trial were purposively sampled. At time point 1 (TP1), 4-6 months after initiation of ICTS, 26 patients were interviewed individually. At time point 2 (TP2), at least one year after treatment initiation, 14 patients of the same study sample participated in 1 out of 3 focus groups. Each interview was audio-recorded, literally transcribed and thematically coded using the constant comparative method. <h3>Results</h3> Four main themes were observed regarding patients9 experiences with ICTS. Firstly, patients expressed preoccupations and feelings about ICTS that changed between both time points, such as fear of side effects at TP1 that diminished at TP2. Secondly, the need for additional information differed among individual patients and shifted from TP1 to TP2. The sources of information most commonly used over time were HPs, relatives and the Internet. Thirdly, patients reported about their relationship with HPs and the need to trust them to follow their advice, especially at TP1. Lastly, patients described their self-management strategies and how quickly ICTS was integrated into their daily routine. <h3>Conclusions</h3> Patients9 experiences with ICTS changed as they progressed through the early phase of the treatment process. Despite concerns at treatment initiation, most patients expressed positive experiences with ICTS. These study findings could facilitate the application of ICTS in daily clinical practice for eRA. <h3>Acknowledgements</h3> The authors thank all rheumatologists and nurses who allowed us access to their patients and all patients who participated. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.2943
Ablation Versus Amiodarone for Treatment of Persistent Atrial Fibrillation in Patients With Congestive Heart Failure and an Implanted Device
Authors: Luigi Di Biase, Prasant Mohanty, Sanghamitra Mohanty, Pasquale Santangeli, Chintan Trivedi, Dhanunjaya Lakkireddy, Madhu Reddy, Pierre Jais, Sakis Themistoclakis, Antonio Dello Russo, Michela Casella, Gemma Pelargonio, Maria Lucia Narducci, Robert Schweikert, Petr Neuzil, Javier Sanchez, Rodney Horton, Salwa Beheiry, Richard Hongo, Steven Hao, Antonio Rossillo, Giovanni Forleo, Claudio Tondo, J. David Burkhardt, Michel Haissaguerre, Andrea Natale
Journal: Circulation (2016)

Whether catheter ablation (CA) is superior to amiodarone (AMIO) for the treatment of persistent atrial fibrillation (AF) in patients with heart failure is unknown.This was an open-label, randomized, parallel-group, multicenter study. Patients with persistent AF, dual-chamber implantable cardioverter defibrillator or cardiac resynchronization therapy defibrillator, New York Heart Association II to III, and left ventricular ejection fraction <40% within the past 6 months were randomly assigned (1:1 ratio) to undergo CA for AF (group 1, n=102) or receive AMIO (group 2, n=101). Recurrence of AF was the primary end point. All-cause mortality and unplanned hospitalization were the secondary end points. Patients were followed up for a minimum of 24 months. At the end of follow-up, 71 (70%; 95% confidence interval, 60%-78%) patients in group 1 were recurrence free after an average of 1.4±0.6 procedures in comparison with 34 (34%; 95% confidence interval, 25%-44%) in group 2 (log-rank P<0.001). The success rate of CA in the different centers after a single procedure ranged from 29% to 61%. After adjusting for covariates in the multivariable model, AMIO therapy was found to be significantly more likely to fail (hazard ratio, 2.5; 95% confidence interval, 1.5-4.3; P<0.001) than CA. Over the 2-year follow-up, the unplanned hospitalization rate was (32 [31%] in group 1 and 58 [57%] in group 2; P<0.001), showing 45% relative risk reduction (relative risk, 0.55; 95% confidence interval, 0.39-0.76). A significantly lower mortality was observed in CA (8 [8%] versus AMIO (18 [18%]; P=0.037).This multicenter randomized study shows that CA of AF is superior to AMIO in achieving freedom from AF at long-term follow-up and reducing unplanned hospitalization and mortality in patients with heart failure and persistent AF.URL: http://www.clinicaltrials.gov. Unique identifier: NCT00729911.
The Efficacy of Azidothymidine (AZT) in the Treatment of Patients with AIDS and AIDS-Related Complex
Authors: Margaret A. Fischl, Douglas D. Richman, Michael H. Grieco, Michael S. Gottlieb, Paul A. Volberding, Oscar L. Laskin, John M. Leedom, Jerome E. Groopman, Donna Mildvan, Robert T. Schooley, George G. Jackson, David T. Durack, Dannie King
Journal: New England Journal of Medicine (1987)

We conducted a double-blind, placebo-controlled trial of the efficacy of oral azidothymidine (AZT) in 282 patients with the acquired immunodeficiency syndrome (AIDS) manifested by Pneumocystis carinii pneumonia alone, or with advanced AIDS-related complex. The subjects were stratified according to numbers of T cells with CD4 surface markers and were randomly assigned to receive either 250 mg of AZT or placebo by mouth every four hours for a total of 24 weeks. One hundred forty-five subjects received AZT, and 137 received placebo. When the study was terminated, 27 subjects had completed 24 weeks of the study, 152 had completed 16 weeks, and the remainder had completed at least 8 weeks. Nineteen placebo recipients and 1 AZT recipient died during the study (P<0.001). Opportunistic infections developed in 45 subjects receiving placebo, as compared with 24 receiving AZT. The base-line Karnofsky performance score and weight increased significantly among AZT recipients (P<0.001). A statistically significant increase in the number of CD4 cells was noted in subjects receiving AZT (P<0.001). After 12 weeks, the number of CD4 cells declined to pretreatment values among AZT recipients with AIDS but not among AZT recipients with AIDS-related complex. Skin-test anergy was partially reversed in 29 percent of subjects receiving AZT, as compared with 9 percent of those receiving placebo (P<0.001). These data demonstrate that AZT administration can decrease mortality and the frequency of opportunistic infections in a selected group of subjects with AIDS or AIDS–related complex, at least over the 8 to 24 weeks of observation in this study. (N Engl J Med 1987; 317:185–91.)
Missed Pneumothorax Seen on Ventilation–Perfusion Scan
Authors: JUSTIN Q. LY
Journal: Clinical Nuclear Medicine (2002)

From the Department of Radiology and Nuclear Medicine, Wilford Hall Medical Center, San Antonio, Texas Received for publication October 29, 2001. Revision accepted January 18, 2002. Reprint requests: Justin Q. Ly, Department of Radiology and Nuclear Medicine, Wilford Hall USAF Medical Center, 759th MDTS/MTRD, 2200 Bergquist Drive, Suite 1, San Antonio, Texas 78236-5300. E-mail: [email protected]
A6.08 Transcriptome profiling by next generation sequencing of hematopoietic progenitors in murine systemic lupus erythematosus (SLE)
Authors: A Banos, M Grigoriou, P Verginis, P Pavlidis, G Bertsias, DT Boumpas
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background and objectives</h3> Hematopoietic Stem Cells (HSCs) give rise to all blood cell lineages, which have been implicated in the pathogenesis of Systemic Lupus Erythematosus (SLE). We reasoned that the fundamental immune aberrations in SLE –genetic or epigenetic- may be more facile to be traced back to the HSC population. <h3>Materials and methods</h3> HSCs were isolated from either healthy C57/BL6 or NZBxNZW/F1 lupus prone mice bone marrow (n = 15 ± 5). The selection markers used are Lin<sup>-</sup>Sca-1<sup>+</sup>c-Kit<sup>+</sup> for LSK compartment, including both long and short term HSCs. Flow cytometry cell sorting of the aforementioned populations was utilised for enumeration, RNA extraction and cell cultures. Finally, paired-end RNA-sequencing analysis was performed with HiSeq 2000 platform. <h3>Results</h3> We identified significantly increased frequencies (˜3% pre-diseased vs ˜5% diseased, p &lt; 0.05) as well as absolute numbers (80–100×10<sup>3</sup> pre-diseased vs 100–150 ×10<sup>3</sup> diseased, p &lt; 0.05) of HSCs in the BM of lupus NZBxNZW/F1 mice with established disease as compared to young pre-diseased NZBxNZW/F1 or control C57/BL6 mice. Bone marrow populations such as hematopoietic stem progenitors cells (HSPCs), lymphoid and myeloid lineages differed in homogeneity depending upon either age or disease, suggesting alterations in HSC potential under inflammatory conditions. Accordingly, serum from F1 young mice promoted healthy HSCs to proliferation and skewed their differentiation towards to myeloid lineage. Transcriptome analysis by RNA-seq of HSCs from lupus mice revealed 294 differentially expressed genes (DEGs) (FC &gt;&nbsp;1.5, q &lt;&nbsp;0.05) in diseased lupus mice compared to pre-diseased. DEGs show enrichment in transcription factors involved in hematopoiesis (Arid3a, Runx2), regulation of immune responses during inflammation and autoimmune diseases (Irf4, Maf) and HSC function and homeostasis (Cxcl<sup>2</sup>, Vegfa, Fbxw7). <h3>Conclusions</h3> These data provide initial insights in the fundamental changes and the molecular identity of HSCs in lupus within the inflammatory milieu of the disease, regulated by a complex transcriptional network.
Abstract LB-57: Multiplexed detection of phospho-ERK as a marker of H-Ras signaling, EGFR and cancer stem cell marker expression in breast cancer cells recovered from human blood
Authors: Arunasalam Navaraj, David T. Dicker, Nathan Dolloff, Wafik S. El-Deiry
Journal: Cancer Research (2011)

Abstract Breast cancer is the most frequent malignancy among women, causing 373,000 deaths per year worldwide. Recent studies indicate that breast cancer is initiated by breast cancer stem cells (BCSCs) which express CD44+/high CD24−/low surface markers. Mammospheres are non-adherent spherical cell clusters grown in selective culture conditions. Our experimental results using mammosphere cultures of different metastatic, human breast cancer cells such as MDA-MB-231 and MDA-MB-468, showed drastic enrichment of breast cancer stem-like cells with the phenotype of CD44+/high CD24−/low in flow cytometry analysis, with specific antibody conjugates. Using the FDA-approved Veridex CellSearch System, we successfully recovered Epcam+/cytokeratin+/CD45− breast cancer cells from 7.5 ml of human blood to which a known number of MDA-MB-468 or H-Ras transformed MCF10A cells had been added. When these recovered breast cancer cells were subjected to Q-Dot conjugated p-ERK antibody staining and quantification, signal intensity clearly demonstrated higher levels of nuclear p-ERK in MCF10A-Ras cells whereas immunostaining for surface EGFR expression was much stronger in MDA-MB-468 cells. We are modeling mammosphere-derived breast cancer cells enriched for stem cell markers by orthotopic implantation into mammary fat pads of nude mice, sampling blood from tumor-bearing animals to detect the presence of Circulating Tumor Cells (CTCs) using the Veridex CellSearch System and further for breast cancer specific multiplexed marker analysis. These stem cell marker enriched xenografted human breast tumors are facilitating our understanding of cellular signaling pathways active in CTCs, and also in understanding of the role of cancer stem cells in human breast cancer metastasis. 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 LB-57. doi:10.1158/1538-7445.AM2011-LB-57
Failure of High-Dose Vitamin C (Ascorbic Acid) Therapy to Benefit Patients with Advanced Cancer
Authors: Edward T. Creagan, Charles G. Moertel, Judith R. O'Fallon, Allan J. Schutt, Michael J. O'Connell, Joseph Rubin, Stephen Frytak
Journal: New England Journal of Medicine (1979)

One hundred and fifty patients with advanced cancer participated in a controlled double-blind study to evaluate the effects of high-dose vitamin C on symptoms and survival. Patients were divided randomly into a group that received vitamin C (10 g per day) and one that received a comparably flavored lactose placebo. Sixty evaluable patients received vitamin C and 63 received a placebo. Both groups were similar in age, sex, site of primary tumor, performance score, tumor grade and previous chemotherapy. The two groups showed no appreciable difference in changes in symptoms, performance status, appetite or weight. The median survival for all patients was about seven weeks, and the survival curves essentially overlapped. In this selected group of patients, we were unable to show a therapeutic benefit of high-dose vitamin C treatment.