tbuckley/cabot-search huggingface dataset:
Abstract 1564: Evaluation and characterization of anti-RalA autoantibody as a potential biomarker in human prostate cancer
Authors: jitian li, Liping Dai, Carlos A. Casiano, Jianying Zhang
Journal: Cancer Research (2015)

Abstract Autoantibodies against intracellular tumor associated antigens (TAAs) are commonly found in various types of human cancers. Their utility in providing insights into tumor biology and as potential cancer biomarkers is well documented. In this study, serum autoantibodies to the Ras family small GTP binding protein (RalA) were detected by immunofluorescence assay, enzyme-linked immunosorbent assay (ELISA), and immunoblotting in 353 sera from patients with prostate cancer (PCa), benign prostatic hyperplasia (BPH), and normal controls. Expression of RalA in prostate tumor tissues was evaluated by immunohistochemistry. The cumulative positive rate of autoantibodies against RalA in PCa reached 18.4%, higher than that in sera with BPH (14.7%) and normal human sera (NHS) (2.25%, P&amp;lt;0.01). Twenty seven of 32 (84.4%) sera with positive OD values were consistently positive in immunoblots. The sensitivity and specificity of anti-RalA antibody in PCa detection was 18.4% and 97.8%, respectively. Representative PCa sera showed a cytoplasmic immunofluorescence staining pattern, with more intense staining in the perinuclear regions or partial staining in intracellular membrane. This pattern was similar to that produced by monoclonal RalA antibody. Strong expression of RalA was observed in 76.5% of prostate tumor tissues. Anti-RalA and PSA simultaneously used as diagnostic markers improved the sensitivity of PCa detection to 57.4%. In addition, the appearance of autoantibodies to RalA was assessed over time in the serially collected samples after surgery in cases. In all cancer patients with anti-RalA positive, autoantibodies were detected in 6 of 54 serial samples taken after surgery with a median lead time of 121 days (Interquartile Range, IQR 0-360). In conclusion, autoantibody to RalA might be a potential serological biomarker for the immunodiagnosis of early stage PCa. We are currently identifying additional novel TAAs targeted by serum autoantibodies in PCa by using two-dimensional gel electrophoresis (2DE) and liquid chromatography-tandem-mass spectrometry (LC-MS/MS). The combination of RalA with PSA, and with other antigens in PCa-specific TAA arrays has the potential for significantly improving the sensitivity of early PCa detection and management in diverse populations. Key words: anti-RalA autoantibody; tumor-associated antigens (TAAs); cancer immunodiagnosis; prostate cancer Citation Format: jitian li, Liping Dai, Carlos A. Casiano, Jianying Zhang. Evaluation and characterization of anti-RalA autoantibody as a potential biomarker in human prostate cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1564. doi:10.1158/1538-7445.AM2015-1564
Abstract 16021: A Changing and Complex Phenotype of Heart Failure in the Community Setting: Trends in Comorbidity, Disability, and Polypharmacy
Authors: Catherine Y Wong, Sarwat I Chaudhry, Mayur M Desai, Harlan M Krumholz
Journal: Circulation (2010)

Background: There is growing concern that clinical practice guidelines fail to adequately address the complexity of patients with heart failure. Patients with heart failure are generally older, and...
Concurrent assessment of vasculature and proliferative pharmacodynamics in patients treated with VEGFR TKI.
Authors: R. Jeraj, G. Liu, U. Simoncic, M. Vanderhoek, S. Perlman, D. B. Alberti, M. R. Harrison, G. Wilding
Journal: Journal of Clinical Oncology (2010)

3050 Background: Proliferation rebound during VEGFR TKI withdrawal has been reported. Pharmacodynamic (PD) study of this phenomenon was conducted using [18F]-fluoro-3'-deoxy-3'-L-fluorothymidine (FLT) PET/CT. On a subset of patients with adequate FLT tumor uptake, kinetic analysis was performed enabling concurrent assessment of tumor proliferation and vasculature status. Methods: Patients with advanced solid malignancies have been enrolled in two separate PD clinical trials using VEGFR TKI (sunitinib [SU] and axitinib [AX]). All patients received the same treatment schedule (2 weeks on, 1 week off). Dynamic and whole body FLT PET/CT scans were obtained at the baseline, Wk 2 (peak VEGFR TKI), and Wk 3 (off VEGFR TKI). A detailed assessment of rebound PD was conducted on a subset of Axitinib patients by performing two FLT PET/CT scans during the withdrawal. Average values of kinetic parameters (k1- perfusion/permeability, vB-blood volume, Ki-proliferation) over the delineated tumor region are reported. Results: 10 subjects (SU) and 10 subjects (AX) have been enrolled. 7 subjects (SU) and 7 subjects (AX) had the FLT uptake suitable for kinetic analysis. Perfusion showed a decrease during the exposure followed by a rebound during the withdrawal (SU: −30%, +55%; AX: −20%, +45%). Blood volume showed consistent increase (SU: +10%, +20%; AX: +10%, 0%). The vasculature PD paralleled the proliferative PD (SU: −20%, +45%; AX: −10%, +50%). Detailed assessment of rebound PD in Axitinib patients revealed the complexity of the phenomena (perfusion: +8% to −2%/day, blood volume: +9% to +100%/day, proliferation: −1% to +6%/day). Conclusions: Concurrent assessment of vasculature and proliferative PD in patients treated with VEGFR TKI revealed complex behavior. The observed PD of tumor proliferation and vascular perfusion/fraction may explain the negative results of concurrent VEGFR TKI and cytotoxic chemotherapy trials. The dynamics of the rebound should be considered in the design of optimal treatment schedules of sequential therapies. No significant financial relationships to disclose.
Atherosclerosis in Ancient Egyptian Mummies
Authors: Adel H. Allam, Randall C. Thompson, L. Samuel Wann, Michael I. Miyamoto, Abd el-Halim Nur el-Din, Gomaa Abd el-Maksoud, Muhammad Al-Tohamy Soliman, Ibrahem Badr, Hany Abd el-Rahman Amer, M. Linda Sutherland, James D. Sutherland, Gregory S. Thomas
Journal: JACC. Cardiovascular imaging (2011)
Field trial of the Global Assessment of Functioning Scale--Modified
Authors: D A Patterson, M S Lee
Journal: American Journal of Psychiatry (1995)

A field trial of the Global Assessment of Functioning Scale--Modified was conducted to test its construct validity. A slightly altered form of the scale, the Social and Occupational Functioning Assessment Scale, was used in DSM-IV.Social, occupational, and clinical data on 196 subjects receiving outpatient mental health services were analyzed.Six significant predictors were found that accounted for 51.75% of the variation in scores on the Global Assessment of Functioning Scale--Modified. Scores were independent of axis I, axis II, and psychoactive substance dependence diagnoses from DSM-III-R.The construct validity of the Global Assessment of Functioning Scale--Modified and the Social and Occupational Functioning Assessment Scale is supported by these findings.
Abstract 1868: Expression of MAS1 in triple-negative breast cancer
Authors: Yi Luo, Yasuhiko Kitadai, Yukiko Nishiguchi, Rina Fujiwara, Takamitsu Sasaki, Hitoshi Ohmori, Hiroki Kuniyasu
Journal: Cancer Research (2015)

Abstract MAS1 is a receptor for angiotensin 1-7 (A1-7), which is derived from angiotensin II (A-II) by the action of angiotensin converting enzyme (ACE) 2. We examined the role of MAS1 in 132 cases of invasive ductal carcinoma (IDC) of the breast by using immunohistochemistry. While normal mammary tissues expressed MAS1 at high levels, MAS1 expression was attenuated in all IDCs, especially in scirrhous IDCs. The decrease in MAS1 expression was associated with tumor growth, lymph node metastasis, and grade. MAS1 expression was inversely associated with the proliferation index and epidermal growth factor receptor and human epidermal growth factor receptor-2 expression. Of the 132 cases, 12 (9.1%) were triple-negative breast cancer (TNBC) cases. Using the mouse TNBC cell line 4T1, which expresses MAS1, we found that cell growth, anti-apoptotic survival, and invasion were suppressed by A1-7 treatment and enhanced by MAS1 knockdown. Combination treatment with cisplatin, an ACE2 activator, and an A-II type 1 receptor blocker showed synergic effects on tumor growth inhibition. These findings suggest that MAS1 might be a pivotal molecular target for TNBC. Note: This abstract was not presented at the meeting. Citation Format: Yi Luo, Yasuhiko Kitadai, Yukiko Nishiguchi, Rina Fujiwara, Takamitsu Sasaki, Hitoshi Ohmori, Hiroki Kuniyasu. Expression of MAS1 in triple-negative breast cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1868. doi:10.1158/1538-7445.AM2015-1868
Differential development of plasmacytoid dendritic cells in Th1- and Th2-like cytokine milieus
Authors: K. Bratke, C. Klein, M. Kuepper, M. Lommatzsch, J. Christian Virchow
Journal: Allergy (2010)

Plasmacytoid dendritic cells (pDCs) infiltrate sites of Th1- and Th2-dominant inflammation and many studies have been performed to analyse their role in these immune responses. In contrast, much less is known about the effects of a Th1 or Th2 cytokine milieu on pDC function. Therefore, we investigated the impact of Th1- and Th2-like conditions during the development of pDCs on their antigen expression and function.PDCs were matured in vitro by the addition of IL-3 under Th1- or Th2-like conditions. Antigen expression and TLR7-ligand-induced cytokine secretion was analysed by flow cytometry and ELISA. Furthermore, the CD4(+) T-cell polarizing capacity of pDCs was determined as well as their potential to induce CD4(+) T-cell proliferation.PDCs matured under Th1-like conditions showed a higher expression of antigens involved in T-cell co-stimulation and antigen presentation like CD40, CD80, CD83 and HLA-DR as well as a higher secretion of IL-6 and IFN-α in response to TLR7-ligation compared to Th2-pDCs. Furthermore, Th1-pDCs induced a significantly higher CD4(+) T-cell proliferation and primed a higher percentage of CD4(+) T cells to express IFN-γ and IL-2 after TLR7-ligation compared to Th2-pDCs. In contrast, Th2-pDCs were characterized by a significant upregulation of BDCA-3 and IL-4 expression following TLR7-ligation.This study is the first to demonstrate the crucial impact of a surrounding cytokine environment on the development of pDC function including antigen expression. Based on these findings, it can be speculated that antiviral/bacterial pDC functions could be impaired during acute allergic conditions.
Abstract 598: Activation of Volume-Sensitive Osmolyte/Anion Channels (VSOACs) Delays Progression from Myocardial Hypertrophy to Heart Failure
Authors: Lihui Liu, Guanlei Wang, Can Yuan, Jiani Xie, William J Hatton, Dayue Duan
Journal: Circulation (2006)

Background: In hypertrophied cardiac myocytes VSOACs become constitutively activated. In this study, we used a murine line targeting ClC-3, a gene encoding native VSOACs in the heart, to explore the molecular mechanism for the potential role of VSOACs in pressure overload-induced myocardial hypertrophy and the progression to heart failure. Methods: A pressure overload model through a minimally invasive transverse aortic banding (MTAB) at the suprasternal notch level was established in age-matched ClCn3−/− mice and their wild-type (WT) littermates. Echocardiography, whole-cell voltage-clamp technique, microarray (Affymetrix chips) and proteomic analysis were used to examine the changes in cardiac phenotype and in gene and protein expression profiles. Results: In 13/16 (81%) left ventricular myocytes isolated from WT mice subjected to MTAB for 5 weeks (wks) a large outwardly rectifying Cl−current was activated under isotonic conditions. Hypotonic cell swelling caused no changes in the current while it was s...
Atopy as a Risk Factor for Chronic Obstructive Pulmonary Disease
Authors: SCOTT T. WEISS
Journal: American Journal of Respiratory and Critical Care Medicine (2000)

Susceptibility to cigarette smoke is not universal. Only 10– 15% of smokers go on to develop chronic obstructive pulmonary disease (COPD). The reasons for this are likely complex and relate primarily to three factors: genetic susceptibility, dose and timing of exposure, and interactions between smoking and other environmental factors of interest in causing the disease. The goal of this article is to consider the epidemiologic data that atopy defined as immediate type II hypersensitivity, and not as clinical asthma, is a risk factor for the development of chronic obstructive lung disease.
Regulation ofp53downstream genes
Authors: Wafik S. El-Deiry
Journal: Seminars in Cancer Biology (1998)

The p53 tumor suppressor is the most commonly mutated gene in human cancer. p53 protein is stabilized in response to different checkpoints activated by DNA damage, hypoxia, viral infection, or oncogene activation resulting in diverse biological effects, such as cell cycle arrest, apoptosis, senescence, differentiation, and antiangiogenesis. The stable p53 protein is activated by phosphorylation, dephosphorylation and acetylation yielding a potent sequence-specific DNA-binding transcription factor. The wide range of p53&apos;s biological effects can in part be explained by its activation of expression of a number of target genes including p21WAF1, GADD45, 14-3-3σ, bax, Fas/APO1, KILLER/ DR5, PIG3, Tsp1, IGF-BP3 and others. This review will focus on the transcriptiona l targets of p53, their regulation by p53, and their relative importance in carrying out the biological effects of p53.
Serum 25-hydroxyvitamin D level, smoking and lung function in adults: the HUNT Study
Authors: Tricia L. Larose, Ben M. Brumpton, Arnulf Langhammer, Carlos A. Camargo, Yue Chen, Pål Romundstad, Xiao-Mei Mai
Journal: European Respiratory Journal (2015)

The association between serum 25-hydroxyvitamin D (25(OH)D) level and lung function changes in the general population remains unclear. We conducted cross-sectional (n=1220) and follow-up (n=869) studies to investigate the interrelationship of serum 25(OH)D, smoking and lung function changes in a random sample of adults from the Nord-Trøndelag Health (HUNT) Study, Norway. Lung function was measured using spirometry and included forced expiratory volume in 1 s (FEV 1 ) % predicted, forced vital capacity (FVC) % pred and FEV 1 /FVC ratio. Multiple linear and logistic regression models estimated the adjusted difference in lung function measures or lung function decline, adjusted odds ratios for impaired lung function or development of impaired lung function and 95% confidence intervals. 40% of adults had serum 25(OH)D levels &lt;50 nmol·L −1 . Overall, those with a serum 25(OH)D level &lt;50 nmol·L −1 showed worse lung function and increased odds of impaired lung function compared to the ≥50 nmol·L −1 group. These associations tended to be stronger among ever-smokers, including greater decline in FEV 1 /FVC ratio and greater odds of the development of impaired lung function (FEV 1 /FVC &lt;70% OR 2.4, 95% CI 1.2–4.9). Associations among never-smokers were null. Results from cross-sectional and follow-up studies were consistent. There were no associations between serum 25(OH)D levels and lung function or lung function changes in never-smokers, whereas significant associations were observed in ever-smokers.
Clinical characteristics, prognostic factors, and outcomes of adult patients with hemophagocytic lymphohistiocytosis
Authors: Zaher K. Otrock, Charles S. Eby
Journal: American Journal of Hematology (2014)

Hemophagocytic lymphohistiocytosis (HLH) is a rare clinical syndrome characterized by the activation of the mononuclear phagocytic system. The diagnosis of HLH in adults is challenging not only because the majority of the reported data are from pediatric patients, but also because HLH occurs in many disease entities. This study reports the clinical and laboratory findings and prognostic factors of adult HLH in a large cohort managed at a single medical center from 2003 to 2014. Seventy-three patients met the HLH-2004 diagnostic criteria. The median age was 51 years (range, 18-82 years); 41 (56.2%) were male. Patients manifested fever, cytopenias, and elevated ferritin in >85% of cases. Likely causes of HLH were as follows: 30 (41.1%) infections, 21 (28.8%) malignancies, 5 (6.8%) attributed to autoimmune disorders, 1 (1.4%) primary immunodeficiency, 2 (2.7%) post solid organ transplantation, and 13 (17.8%) idiopathic. The median overall survival was 7.67 months. Patients with malignancy-associated HLH had a markedly worse survival compared with patients with non-malignancy-associated HLH (median overall survival 1.13 vs. 46.53 months, respectively; P < 0.0001). In a multivariable analysis, malignancy (hazard ratio = 12.22; 95% CI: 2.53-59.02; P = 0.002) correlated with poor survival. Ferritin >50,000 µg/L correlated with 30-day mortality. Survival after a diagnosis of HLH is dismal, especially among those with malignancy-associated HLH. The development of a registry for adults with HLH would improve our understanding of this syndrome, validate diagnostic criteria, and help develop effective treatment strategies.
Characteristics and outcome of warm autoimmune hemolytic anemia in adults: New insights based on a single‐center experience with 60 patients
Authors: Mathilde Roumier, Valentine Loustau, Constance Guillaud, Laetitia Languille, Matthieu Mahevas, Mehdi Khellaf, Nicolas Limal, France Noizat‐Pirenne, Bertrand Godeau, Marc Michel
Journal: American Journal of Hematology (2014)

Warm autoimmune hemolytic anemia (wAIHA) is a rare autoimmune disease with poorly known natural history and management remaining mainly empirical. To better describe the characteristics and outcome of wAIHA in adults, we performed a single‐center cohort study of patients diagnosed with wAIIHA from 2001 to 2012 in our center. Sixty patients (50% women) were included, the mean age at the time of wAIHA onset was 54 ± 23 years. wAIHA was considered “primary” for 21 patients (35%) and was associated with an underlying disorder in 39 (65%), including mainly lymphoproliferative disorders and systemic lupus. All patients but two needed treatment and received corticosteroids, with an overall initial response rate of 87%. However, 63% of the patients were corticosteroid‐dependent and 56% required at least one second‐line treatment including mainly rituximab ( n = 19). At the time of analysis, after a mean follow‐up of 46 months, 28 patients (47%) were in remission and off treatment and 5 (8%) had died. The presence of an underlying lymphoproliferative disorder was associated with reduced response to corticosteroids and increased need for second‐line therapy. In conclusion, in the last decade and compared to a previous series from our center, the rate of secondary wAIHA has increased and the use of rituximab has emerged as the preferred second‐line treatment and corticosteroid‐sparing strategy; the overall mortality has significantly decreased (8 vs. 18%). Am. J. Hematol. 89:E150–E155, 2014. © 2014 Wiley Periodicals, Inc.
Abstract 4405: AXL receptor tyrosine kinase is associated with the prognosis of patients with esophageal squamous cell carcinoma
Authors: Pei-Wen Yang, Min-Shu Hsieh, Ya-Chuan Huang, Tzu-Hsuan Chiang, Jang-Ming Lee
Journal: Cancer Research (2014)

Abstract PURPOSE: The AXL receptor tyrosine kinase has been suggested as a prognostic factor and a therapeutic target in esophageal adenocarcinoma. Whether AXL play some role in the prognosis of esophageal squamous cell carcinoma (ESCC) is unknown. We aim to investigate the association of AXL expression in tumor tissues with the prognosis of patients with ESCC. PATIENTS AND METHODS: The study was analyzed retrospectively. A total of 57 patients diagnosed with ESCC were enrolled in the study. AXL expression in esophageal timorous tissues was detected by immunnohistochemisty (IHC), and was correlated with the overall survival (OS) or progression-free survival (PFS) of patients by multivariate Cox regression analysis and Kaplan-Meier survival function. RESULTS: AXL could be detected in 38 patients (66.7%). Elevated expression of AXL was associated with increased risk of both death and recurrence (HR[95 % CI]=1.46 [1.05-2.04], Ptrend=0.026 in death and HR[95 % CI]=1.75[1.24-2.48], Ptrend=0.002 in recurrence). Patents expressing high levels of AXL (n=25, 43.9 %) exhibited a 2.15 fold increased risk of recurrence compared to those absence or with low level of AXL (HR[95 % CI]=2.15[1.08-4.28], P=0.029). Kaplan-Meier survival function demonstrated that the progression-free duration was significantly different among the patients expressing different levels of AXL (log-rank P=0.029). CONCLUSION: Expression of AXL in esophageal tumor tissues is a prognostic predictor of ESCC. The results revealed AXL could also be a therapeutic target of ESCC. Citation Format: Pei-Wen Yang, Min-Shu Hsieh, Ya-Chuan Huang, Tzu-Hsuan Chiang, Jang-Ming Lee. AXL receptor tyrosine kinase is associated with the prognosis of patients with esophageal squamous cell carcinoma. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4405. doi:10.1158/1538-7445.AM2014-4405
Abstract 17313: Alirocumab, a Proprotein Convertase Subtilisin/Kexin Type 9 Monoclonal Antibody, Reduces Cholesterol Concentrations of All Serum Low-Density Lipoprotein Cholesterol Fractions
Authors: Peter P Toth, Sara Hamon, Steven R Jones, Parag H Joshi, Seth S Martin, Robert Pordy, Corinne Hanotin
Journal: Circulation (2013)

Introduction: Low-density lipoprotein cholesterol (LDL-C) is composed of a variety of LDL particles of different densities and states of lipidation. Analysis of effects of lipid-modifying therapies...