tbuckley/cabot-search huggingface dataset:
Abstract 4421: GPER-mediated activation of the cAMP response element-binding protein (CREB) and subsequent IGFBP-1 expression is altered during the development of tamoxifen resistance
Authors: Ali Vaziri-Gohar, Kevin D. Houston
Journal: Cancer Research (2015)

Abstract Tamoxifen is a commonly prescribed anti-estrogen treatment for breast cancer patients; this selective estrogen receptor modulator functions as an ERα-antagonist in breast tissue and inhibits cell proliferation and survival of breast cancer cells. More recently, the active metabolite of tamoxifen, 4-OHT (Tam), has been shown to activate the G protein-coupled estrogen receptor (GPER). Previous studies from our laboratory identified a novel, GPER-dependent mechanism of Tam action in breast cancer cells that requires the extracellular accumulation of the insulin-like growth factor binding protein-1 (IGFBP-1). The molecular mechanisms of Tam-induced IGFBP-1 production mediated by GPER have not been determined. GPER activation has been shown to stimulate cAMP production and PKA activation in several cell types. We hypothesized the cAMP response element-binding protein (CREB) activation is required for Tam-induced IGFBP-1 production in breast caner cells. To determine if CREB activation may be involved in IGFBP-1 transcription, CREB phosphorylation (S133) status and nuclear accumulation were determined in MCF-7 cells after Tam treatment. The phosphorylation and nuclear accumulation of CREB were observed in Tam-treated MCF-7 cells suggesting that CREB activation may be required for Tam-induced IGFBP-1 transcription. Increased CREB phosphorylation and IGFBP-1 transcription were inhibited by pretreatment with the PKA inhibitor H-89 supporting a role for CREB in Tam-induced IGFBP-1 expression. H-89 pretreatment also significantly decreased the previously reported inhibition of IGF-1-stimulated signaling by Tam treatment in breast cancer cells. We have previously reported that Tam-induced IGFBP-1 expression is dysregulated in Tam-resistant MCF-7 cells (MCF-7TamR). To determine if aberrant CREB signaling results in the observed dysregulation, similar experiments were performed in MCF-7TamR cells. Our results show that CREB phosphorylation and nuclear accumulation are decreased in Tam-resistant cells compared to Tam-sensitive cells. Taken together, these results suggest that activation of GPER results in CREB-dependent IGFBP-1 production and subsequent inhibition of IGF-1-stimulated signaling in breast cancer cells treated with Tam. Furthermore, dysregulation of GPER-mediated CREB activation may be involved in the development of Tam resistance in breast cancer. Citation Format: Ali Vaziri-Gohar, Kevin D. Houston. GPER-mediated activation of the cAMP response element-binding protein (CREB) and subsequent IGFBP-1 expression is altered during the development of tamoxifen resistance. [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 4421. doi:10.1158/1538-7445.AM2015-4421
Survivin and B7-H1 Are Collaborative Predictors of Survival and Represent Potential Therapeutic Targets for Patients with Renal Cell Carcinoma
Authors: Amy E. Krambeck, Haidong Dong, R. Houston Thompson, Susan M. Kuntz, Christine M. Lohse, Bradley C. Leibovich, Michael L. Blute, Thomas J. Sebo, John C. Cheville, Alexander S. Parker, Eugene D. Kwon
Journal: Clinical Cancer Research (2007)

Abstract Purpose: Clear cell renal cell carcinoma (ccRCC) is an immunogenic tumor that can progress in the presence of an intact host immune system. We previously reported that survivin and B7-H1 are independently associated with disease progression and death when expressed by ccRCC tumors. Herein, we examine the clinical effect of ccRCC combined expression of both survivin and B7-H1. Experimental Design: Specimens from 298 patients who underwent nephrectomy for ccRCC between 1990 and 1994 were immunohistochemically stained for survivin and B7-H1. Cancer-specific survival was estimated using the Kaplan-Meier method. Associations of both markers with ccRCC death were assessed using Cox proportional hazards regression models. Results: At last follow-up, 94 patients died from ccRCC. Among the living patients, the median follow-up was 11.2 years (range, 0-15 years). There were 177 (59.4%) survivinLow/B7-H1−, 51 (17.1%) survivinHi/B7-H1−, 29 (9.7%) survivinLow/B7-H1+, and 41 (13.8%) survivinHi/B7-H1+ tumors. The 5-year cancer-specific survival rates for patients within each group were 89.3%, 59.7%, 70.0%, and 16.2%, respectively. Combined survivinHi/B7-H1+ expression was associated with ccRCC death univariately (risk ratio, 12.82; 95% confidence interval, 7.50-21.92; P &amp;lt; 0.001) and in multivariate analysis (risk ratio, 2.81; 95% confidence interval, 1.56-5.04; P &amp;lt; 0.001). SurvivinHi/B7-H1+ tumors exhibited increased levels of infiltrating mononuclear cells and survivin-specific T cells compared with survivinLow/B7-H1− tumors. Conclusion: Patients with survivinHi/B7-H1+ ccRCC tumors are at increased risk of ccRCC death. SurvivinHi/B7-H1+ tumors also harbor increased amounts of infiltrating mononuclear cells and survivin-specific T cells relative to survivinLow/B7-H1− tumors. Taken together, dual expression of survivin and B7-H1 can be used to predict ccRCC tumor aggressiveness.
Myocardial catecholamine content after heart transplantation.
Authors: V Regitz, C Bossaller, R Strasser, S Schüler, R Hetzer, E Fleck
Journal: Circulation (1990)

Myocardial catecholamine levels have not yet been determined in the transplanted human heart. We measured norepinephrine, epinephrine, and dopamine in endomyocardial biopsies from 19 short-term (organ age, 6.6 +/- 6 months) and five long-term (organ age, 62 +/- 2 months) heart transplant patients. Results were compared with those from 10 normal control subjects. In 17 of 19 short-term heart transplant patients, myocardial catecholamines were undetectable, indicating values below 0.1 pg/micrograms noncollagen protein, which was the detection threshold of our assay. In the remaining two patients, myocardial catecholamines (pg/microgram noncollagen protein) were norepinephrine (1.4 and 3.2), epinephrine (0.8 and 1.9), and dopamine (0.9 and 2.3), respectively. In the five long-term heart transplant patients, myocardial catecholamines were not detected. Catecholamine concentrations in 10 healthy control subjects were norepinephrine (10.3 +/- 2.9), epinephrine (0.36 +/- 0.51), and dopamine (0.52 +/- 0.40). Low myocardial norepinephrine levels (less than 20% of control values) with unexplained high levels of epinephrine and dopamine were found in single transplant patients. In most heart transplant patients, however, myocardial catecholamines were undetectable up to five years after transplantation, indicating that the adrenergic response of these hearts probably depends on variations in plasma catecholamines or cardiac beta-receptor density.
Case-control study of 24 hour ambulatory blood pressure in patients with obstructive sleep apnoea and normal matched control subjects
Authors: C. W H Davies
Journal: Thorax (2000)

<h3>BACKGROUND</h3> There is considerable debate regarding the relationship between obstructive sleep apnoea (OSA) and hypertension. It is unclear whether OSA is an independent vascular risk factor as studies attempting to assess this association have produced conflicting results because of confounding variables such as upper body obesity, alcohol, and smoking. A case-control study of 24 hour ambulatory blood pressure was undertaken in patients with OSA and matched controls to assess whether OSA is an independent correlate of diurnal hypertension. <h3>METHODS</h3> Forty five patients with moderate to severe OSA and excessive daytime sleepiness were matched with 45 controls without OSA in a sleep study. Matched variables included age, body mass index (BMI), alcohol, cigarette usage, treated hypertension, and ischaemic heart disease. Upper body obesity was compared by waist:hip and waist:height ratios; 24 hour ambulatory blood pressure recordings were performed (before treatment for OSA) in all subjects. <h3>RESULTS</h3> Patients with OSA had significantly increased mean (SD) diastolic blood pressure (mm Hg) during both daytime (87.4 (10.2) versus 82.8 (9.1); p=0.03, mean difference 4.6 (95% CI 0.7 to 8.6) and night time (78.6 (9.3) versus 71.4 (8.0); p&lt;0.001, mean difference 7.2 (95% CI 3.7 to 10.6)), and higher systolic blood pressure at night (119.4 (20.7) versus 110.2 (13.9); p=0.01, mean difference 9.2 (95% CI 2.3 to 16.1)). The nocturnal reduction in blood pressure (“dipping”) was smaller in patients with OSA than in control subjects. <h3>CONCLUSIONS</h3> Compared with closely matched control subjects, patients with OSA have increased ambulatory diastolic blood pressure during both day and night, and increased systolic blood pressure at night. The magnitude of these differences is sufficient to carry an increased risk of cardiovascular morbidity. The slight excess of upper body fat deposition in the controls may make these results conservative.
MBX-102/JNJ39659100, a Novel Peroxisome Proliferator Activated Receptor-γ Ligand with Weak Transactivation Activity Retains Full Anti-Diabetic Properties in the Absence of Side Effects
Authors: Francine M. Gregoire, Fang Zhang, Holly J. Clarke, Thomas A. Gustafson, Dorothy D. Sears, Svetlana Favelyukis, James Lenhard, Dennis Rentzeperis, L. Edward Clemens, Yi Mu, Brian E. Lavan
Journal: Endocrine Reviews (2009)

ABSTRACT MBX-102/JNJ39659100 (MBX-102) is in clinical development as an oral glucose lowering agent for the treatment of type 2 diabetes. MBX-102 is a non-thiazolidinedione (TZD) selective partial agonist of PPAR-γ that is differentiated from the TZDs structurally, mechanistically, pre-clinically and clinically. In diabetic rodent models, MBX-102 has insulin sensitizing and glucose lowering properties comparable to TZDs without dose-dependent increases in body weight. In vitro, in contrast with full PPAR-γ agonist treatment, MBX-102 fails to drive human and murine adipocyte differentiation and selectively modulates the expression of a subset of PPAR-γ target genes in mature adipocytes. Moreover, MBX-102 does not inhibit oteoblastogenesis of murine mesenchymal cells. Compared to full PPAR-γ agonists, MBX-102 displays differential interactions with the PPAR-γ ligand binding domain (LBD) and possesses reduced ability to recruit coactivators. Interestingly, in primary mouse macrophages, MBX-102 displays enhanced anti-inflammatory properties compared to other PPAR-γ or α/γ agonists suggesting that MBX-102 has more potent transrepression activity. In summary, MBX-102 is a selective PPAR-γ modulator with weak transactivation but robust transrepression activity. MBX-102 exhibits full therapeutic activity without the classical PPAR-γ side effects and may represent the next generation insulin sensitizer.
Tibial Nerve Stimulation for Treating Neurogenic Lower Urinary Tract Dysfunction: A Systematic Review
Authors: Marc P. Schneider, Tobias Gross, Lucas M. Bachmann, Bertil F.M. Blok, David Castro-Diaz, Giulio Del Popolo, Jan Groen, Rizwan Hamid, Gilles Karsenty, Jürgen Pannek, Lisette ‘t Hoen, Thomas M. Kessler
Journal: European Urology (2015)
An Evaluation of the Incidence of Adverse Events by Subcutaneous Versus Intravenous Administration of Bortezomib
Authors: Shoko Hisama, Kisato Nosaka, Yumiko Yano, Naomi Mori, Yasuko Okamoto, Yutaka Okuno, Hirotaka Iwase
Journal: Annals of Oncology (2014)
Detection of mRNAs for macrophage products in inflammatory bowel disease by in situ hybridisation.
Authors: M Cappello, S Keshav, C Prince, D P Jewell, S Gordon
Journal: Gut (1992)

<b>Introduction:</b> The patient survival is closely related to the presence of chronic rejection. <b>Objectives:</b> To determine the association between tacrolimus levels in the first two weeks post-transplant and the presence of rejection during the first year. <b>Materials and methods:</b> A retrospective study of 185 lung transplant patients was performed. The mean and median of all levels of tacrolimus in the first 15 days post-transplant were analyzed, determining: low level &lt;10 mcg / uL, appropriate level 10-15 mcg / uL and high level&gt; 15 mcg / uL. <b>Results:</b> A total of 146 patients were analyzed (26 patients died during the first year and 13 were switched of immunosuppressive therapy). The mean level of tacrolimus was 11,96 with a SD of 4.84 (p &lt;0.001) and the median was 10.75 with a SD 3.37 (p 0.33). A 45.21% had acute cellular rejection in the third week post-transplant and the first year showed 32.41% rejection. Until the third week post-transplant 69.87% patients had low levels, of these 45,21% presented rejection; 18.49% had adequate level, with a 40% of rejection; and 11.64% had high levels of these 52.9% presented rejection. The first year post-transplant and according to levels, low, adequate or high, the patients who experienced rejection were 60.7%, 44.44% and 64.7% respectively. Wilcoxon analysis: "W" -10.480 (p &lt;0.00). <b>Conclusions:</b> For this study and according to analyzes, there could be a relationship between the levels of tacrolimus during the firsts two weeks post-transplant and the presence of rejection during the first year, as we can see in the frequencies of the low and high tacrolimus levels groups compared with the adequate group.
Human CD4 restores normal T cell development and function in mice deficient in murine CD4.
Authors: Y M Law, R S Yeung, C Mamalaki, D Kioussis, T W Mak, R A Flavell
Journal: The Journal of Experimental Medicine (1994)

The ability of a human coreceptor to function in mice was investigated by generating human CD4 (hCD4)-expressing transgenic mice on a mouse CD4-deficient (mCD4-/-) background. From developing thymocyte to matured T lymphocyte functions, hCD4 was shown to be physiologically active. By examining the expansion and deletion of specific V beta T cell families in mutated mice with and without hCD4, it was found that hCD4 can participate in positive and negative selection. Mature hCD4 single positive cells also were found in the periphery and they were shown to restore MHC class II-restricted alloreactive and antigen-specific T cell responses that were deficient in the mCD4 (-/-) mice. In addition, these hCD4 reconstituted mice can generate a secondary immunoglobulin G humoral response matching that of mCD4 wild-type mice. The fact that human CD4 is functional in mice and can be studied in the absence of murine CD4 should facilitate studies of human CD4 activity in general and human immunodeficiency virus 1 gp120-mediated pathogenesis in acquired immune deficiency syndrome specifically.
A computed tomography radiogenomic biomarker predicts microvascular invasion and clinical outcomes in hepatocellular carcinoma
Authors: Sudeep Banerjee, David S. Wang, Hyun J. Kim, Claude B. Sirlin, Michael G. Chan, Ronald L. Korn, Aaron M. Rutman, Surachate Siripongsakun, David Lu, Galym Imanbayev, Michael D. Kuo
Journal: Hepatology (2015)

Microvascular invasion (MVI) in hepatocellular carcinoma (HCC) is an independent predictor of poor outcomes subsequent to surgical resection or liver transplantation (LT); however, MVI currently cannot be adequately determined preoperatively. Radiogenomic venous invasion (RVI) is a contrast-enhanced computed tomography (CECT) biomarker of MVI derived from a 91-gene HCC "venous invasion" gene expression signature. Preoperative CECTs of 157 HCC patients who underwent surgical resection (N = 72) or LT (N = 85) between 2000 and 2009 at three institutions were evaluated for the presence or absence of RVI. RVI was assessed for its ability to predict MVI and outcomes. Interobserver agreement for scoring RVI was substantial among five radiologists (κ = 0.705; P < 0.001). The diagnostic accuracy, sensitivity, and specificity of RVI in predicting MVI was 89%, 76%, and 94%, respectively. Positive RVI score was associated with lower overall survival (OS) than negative RVI score in the overall cohort (P < 0.001; 48 vs. >147 months), American Joint Committee on Cancer tumor-node-metastasis stage II (P < 0.001; 34 vs. >147 months), and in LT patients within Milan criteria (P < 0.001; 69 vs. >147 months). Positive RVI score also portended lower recurrence-free survival at 3 years versus negative RVI score (P = 0.001; 27% vs. 62%).RVI is a noninvasive radiogenomic biomarker that accurately predicts histological MVI in HCC surgical candidates. Its presence on preoperative CECT is associated with early disease recurrence and poor OS and may be useful for identifying patients less likely to derive a durable benefit from surgical treatment.
Virtual Electrode–Induced Reexcitation
Authors: Yuanna Cheng, Kent A. Mowrey, David R. Van Wagoner, Patrick J. Tchou, Igor R. Efimov
Journal: Circulation Research (1999)

Abstract —Mechanisms of defibrillation remain poorly understood. Defibrillation success depends on the elimination of fibrillation without shock-induced arrhythmogenesis. We optically mapped selected epicardial regions of rabbit hearts (n=20) during shocks applied with the use of implantable defibrillator electrodes during the refractory period. Monophasic shocks resulted in virtual electrode polarization (VEP). Positive values of VEP resulted in a prolongation of the action potential duration, whereas negative polarization shortened the action potential duration, resulting in partial or complete recovery of the excitability. After a shock, new propagated wavefronts emerged at the boundary between the 2 regions and reexcited negatively polarized regions. Conduction velocity and maximum action potential upstroke rate of rise dV/dt max of shock-induced activation depended on the transmembrane potential at the end of the shock. Linear regression analysis showed that dV/dt max of postshock activation reached 50% of that of normal action potential at a V m value of −56.7±0.6 mV postshock voltage (n=9257). Less negative potentials resulted in slow conduction and blocks, whereas more negative potentials resulted in faster conduction. Although wavebreaks were produced in either condition, they degenerated into arrhythmias only when conduction was slow. Shock-induced VEP is essential in extinguishing fibrillation but can reinduce arrhythmias by producing excitable gaps. Reexcitation of these gaps through progressive increase in shock strength may provide the basis for the lower and upper limits of vulnerability. The former may correspond to the origination of slow wavefronts of reexcitation and phase singularities. The latter corresponds to fast conduction during which wavebreaks no longer produce sustained arrhythmias.
Low birth weight and later development of insulin resistance and biochemical/clinical features of polycystic ovary syndrome
Authors: Caterina Pandolfi, Antonella Zugaro, Francesca Lattanzio, Stefano Necozione, Arcangelo Barbonetti, Maria Simonetta Colangeli, Sandro Francavilla, Felice Francavilla
Journal: Metabolism (2008)
Heritability of Longitudinal Change in Lung Function
Authors: DANIEL J. GOTTLIEB, JEMMA B. WILK, MICHAEL HARMON, JANE C. EVANS, OSCAR JOOST, DANIEL LEVY, GEORGE T. O'CONNOR, RICHARD H. MYERS
Journal: American Journal of Respiratory and Critical Care Medicine (2001)

There have been multiple reports of heritability of lung function in cross-sectional analysis, but no prior reports of heritability of rate of change in lung function. We examined heritability of rate of change of lung function in families participating in the Framingham Heart Study. Spirometric measures from two time points were used to calculate annualized rate of change in FEV1, FVC, and FEV1/FVC ratio, adjusting for the effects of age, height, and weight using multiple linear regression models. Standardized residuals from these models were used as phenotypic variables in variance components analysis to assess effects of smoking and heritable factors on rate of change in lung function. Heritable factors explained a modest proportion of the population variance, with heritability estimates for change in FEV1, FVC, and ratio of 0.05, 0.18, and 0.13, respectively. Restricting the analysis to subjects concordant for smoking status during the interval over which lung function was measured, the heritability estimates increased to 0.18, 0.39, and 0.14, respectively, among interim smokers. These data suggest that in middle-aged and older persons in the general population, genetic factors contribute modestly to the overall population variance in rate of lung function decline, and further suggest the importance of gene–environment interactions.
THE LS-ANTIGEN OF VACCINIA
Authors: Joseph E. Smadel, Thomas M. Rivers
Journal: The Journal of Experimental Medicine (1942)

Experimental data are presented which may be interpreted as follows. The heat-labile (L) and heat-stable (S) antigens of vaccinia occur in nature as a complex consisting of a single substance with two serologically active parts, each of which may be degraded independently of the other.
Incidence of Type 1 Diabetes in Lithuanians Aged 0–39 Years Varies by the Urban-Rural Setting, and the Time Change Differs for Men and Women During 1991–2000
Authors: Auste Pundziute-Lyckå, Brone Urbonaite, Rytas Ostrauskas, Rimas Zalinkevicius, Gisela G. Dahlquist
Journal: Diabetes Care (2003)

OBJECTIVE—Type 1 diabetes has been associated with factors related to welfare and social class. During the past decade, Lithuania has experienced a transition period, leading to dramatic changes in the socioeconomic structure of the society. RESEARCH DESIGN AND METHODS—Incidence in the group aged 0–39 years by urban-rural setting (cities &amp;gt;100,000 inhabitants, towns, and rural areas), period (1991–1995 and 1996–2000), age, and sex were studied using Poisson regression. RESULTS—The age- and sex-standardized incidence per 100,000 inhabitants per year was higher in men aged 0–39 years than in women (9.5 and 6.9, respectively, incidence rate ratio [IRR] = 1.39, P &amp;lt; 0.001). Incidence was lower in rural areas than in towns and cities (7.1, 9.0, and 8.8, respectively, P &amp;lt; 0.001). The urban-rural differences in incidence were most marked among children aged 0–9 years. From 1991–1995 to 1996–2000, the overall incidence increased from 8.7 to 10.5 (IRR = 1.22, P = 0.001) in men and from 6.2 to 7.8 (IRR = 1.25, P = 0.002) in women. For men, the increase over time occurred predominantly in the cities, from 8.4 to 11.8 (IRR = 1.40, P &amp;lt; 0.001), and in the older age-groups. In contrast, for women, the incidence increased more in small towns and rural areas, from 5.8 to 7.7 (IRR = 1.33, P = 0.003), and in the younger age-groups. CONCLUSIONS—The incidence of type 1 diabetes in Lithuania differs depending on the urban-rural setting, and the pattern of change over time differs between the sexes, both by urban-rural setting and age-group. The findings support the theory that lifestyle-related factors connected to socioeconomic status are important for the occurrence of type 1 diabetes.