tbuckley/cabot-search huggingface dataset:
Abstract 1713: Activation of the aryl hydrocarbon receptor and down-regulation of the androgen receptor in prostate cancer cells by the curcumin analog C48
Authors: Alexandra M. Fajardo, Harmony J. Bowles, Debra A. MacKenzie, David L. Vander Jagt, Marco Bisoffi, Todd A. Thompson
Journal: Cancer Research (2010)

Abstract The androgen receptor (AR) is a critical player in prostate cancer (CaP) development and progression and is a well-established therapeutic target. Recent studies have shown the aryl hydrocarbon receptor (AhR) is an important modulator of the AR acting as an adaptor for ubiquitin ligases and increasing the degradation of the AR. The natural product curcumin, a known inhibitor of the AR, has been shown to modulate the activity of the AhR. We have identified a curcumin analog, C48, which potently inhibits CaP cell proliferation. The purpose of this study was to identify molecular pathways that contribute to the effects of C48 on CaP cells, which may involve AR down-regulation through an AhR-mediated mechanism. Androgen-sensitive LAPC4, LNCaP and C4-2 CaP cells were used to perform these studies. We have found that C48 potently reduces AR expression levels in CaP cells in a dose- and time-dependent manner. C48 also decreased expression of genes induced by the AR, such as prostate specific antigen. We have found that a potent AhR activator, benzo(a)pyrene, down-regulates AR protein expression in CaP cells. As with benzo(a)pyrene, C48 was found to activate the AhR as determined using an AhR-activated reporter system. In addition, C48 potently induced markers of AhR activation including cytochrome P450 1A1 and aldoketoreductase 1C1 in CaP cells. Previous studies (e.g., Fritz et al., 2007) have shown that the AhR may act as a prostate cancer suppressor. Results from this study may facilitate the identification of safe and effective agents, such as the curcumin analog C48, that target AR down-regulation as a potential therapeutic strategy for prostate cancer without the toxicities associated with agents such as benzo(a)pyrene. 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 1713.
Hypertension in Children
Authors: Alan R. Sinaiko
Journal: New England Journal of Medicine (1996)

The measurement of blood pressure is now firmly established as an important component of the routine pediatric physical examination. Nevertheless, blood pressure in children has been given serious attention only since the mid-1960s. The first report of the Task Force on Blood Pressure Control in Children was published in 1977.1 The long-term natural history of blood pressure in children is not well understood. Norms for blood pressure and definitions of hypertension were revised and strengthened by the second task force report, published in 1987,2 and a recent revision contains modified recommendations and norms.3 Factors Influencing Blood Pressure in ChildhoodBlood . . .
Tc-99m MAA Perfusion Lung Scanning in Hepatopulmonary Syndrome
Authors: YOSHIHIRO NISHIYAMA, YUKA YAMAMOTO, KATASHI SATOH, MOTOOMI OHKAWA, YOSHIKI MOROTOMI, MASATADA TANABE
Journal: Clinical Nuclear Medicine (1999)

A patient with the hepatopulmonary syndrome with extrapulmonary Tc-99m macroaggregated albumin (MAA) accumulation and a segmental perfusion defect is described. Tc-99m MAA imaging in patients with hepatopulmonary syndrome typically shows heterogeneous pulmonary perfusion. Segmental defects that mimic pulmonary embolism have also been reported.
Tc-99m MDP Uptake in Soft Tissue Extraskeletal Metastasis From Osteogenic Sarcoma
Authors: WILLIAM M. PACE, I. ROSS McDOUGALL
Journal: Clinical Nuclear Medicine (2000)

A bone scan in a patient with proved osteogenic sarcoma of the tibia showed intense focal uptake in the gluteal region on the side of his cancer. This was proved to be a metastasis in the muscle.
Glomerular and Dermal Deposition of Properdin in Systemic Lupus Erythematosus
Authors: Naomi Rothfield, H. Arlene Ross, Joe O. Minta, Irwin H. Lepow
Journal: New England Journal of Medicine (1972)

Abstract Properdin was demonstrated by indirect immunofluorescence in glomeruli of six of seven patients with lupus nephritis, two of whom had membranous lupus nephritis, one focal proliferative lu...
Identification of a Brazil-Nut Allergen in Transgenic Soybeans
Authors: Julie A. Nordlee, Steve L. Taylor, Jeffrey A. Townsend, Laurie A. Thomas, Robert K. Bush
Journal: New England Journal of Medicine (1996)

The nutritional quality of soybeans (Glycine max) is compromised by a relative deficiency of methionine in the protein fraction of the seeds. To improve the nutritional quality, methionine-rich 2S albumin from the Brazil nut (Bertholletia excelsa) has been introduced into transgenic soybeans. Since the Brazil nut is a known allergenic food, we assessed the allergenicity of the 2S albumin.
RT-35 * ELAPSED DAYS AFTER RADIOTHERAPY FOR GLIOBLASTOMA
Authors: T. Wang, A. Jani, S. Saad, Y. Qureshi, J. Estrada, M. Sisti, J. Bruce, G. McKhann, S. Cheng, K. S. Clifford Chao, A. Lassman, S. Isaacson
Journal: Neuro-Oncology (2014)

BACKGROUND: There have been conflicting reports regarding the effect of delayed radiation therapy after surgical resection of glioblastoma (GBM) on outcomes. We sought to investigate whether the timing of adjuvant radiotherapy (RT) impacted survival of patients at our institution. METHODS: We reviewed all patients treated with radiotherapy for GBM at our institution. Variables included in our analysis were age, Karnofsky Performance Status (KPS), type of surgery, length of hospital stay, receipt of temozolomide (TMZ), RT duration, RT technique, total RT dose, interval between surgery and RT, and tumor molecular status including isocitrate dehydrogenase 1 (IDH-1) and O-6-methylguanine-DNA methyltransferase (MGMT). Survival was calculated using the Kaplan-Meier Method. RESULTS: From 1998 to 2013, 419 GBM patients were treated with radiotherapy of which 239 were men (57.0%). The median age was 60 years (range 18–91). The median survival for the entire cohort was 339 days (11.1 months). 151 patients started radiotherapy after surgery <3 weeks (36.0%), 181 patients between 3-5 weeks (43.2%) and 87 patients >5 weeks (20.8%). On univariate analysis age, KPS, type of surgery, length of hospital stay, RT duration, RT technique, total dose and interval between surgery and RT were significant predictors of mortality. IDH-1 (p = 0.17) and MGMT (p = 0.18) mutated status showed a trend towards better survival. Patients who started RT <3 weeks had worse survival than those starting between 3-5 weeks and >5 weeks after surgery with the 1-year actuarial overall survival: 52.4%, 63.6% and 63.9%, respectively. On multivariate analysis only age, KPS, type of surgery, and total RT dose were significant predictors of survival; while interval between surgery and RT was not. CONCLUSIONS: We observed no detriment to delaying RT after surgical resection of GBM, and in fact, a small benefit to deferring RT until 3 weeks after surgery was observed on univariate analysis.
S141 Tumour Necrosis Factor Receptor 1 Shedding Is Related To Acute Skeletal Muscle Wasting In Critical Illness
Authors: Z. Puthucheary, J. Rawal, M. McPhail, T. Dew, R. Phadke, A. Rowlerson, S. Harridge, H. Montgomery, N. Hart
Journal: Thorax (2014)

<h3>Introduction</h3> Muscle wasting occurs early and rapidly in critically ill patients. It results from a decrease in muscle protein synthesis and an increase in its breakdown, with muscle necrosis a common associated finding. The drivers for such atrophy and necrosis remain poorly understood, as do the related regulatory pathways. We hypothesised that systemic and intracellular cytokines play a role in this process. <h3>Methods</h3> The UK-MUSCLE study prospectively studied the wasting response (change in Rectus Femoris cross sectional area (RF<sub>CSA</sub>) using serial ultrasound) in critically ill patients admitted to the ICU. Cytokine profiles (high sensitivity cytokine chip array, Randox, Ireland) were analysed in serum samples from 62 of these patients (days 1 and 7) and in contemporaneous Vastus Lateralis biopsies of 35 patients. Tumour Necrosis Factor (TNF)-α, TNF receptor (TNFR) 1 and 2, interleukin (IL)1a, il1b, IL-2, IL-4, IL-6, IL-8, IL-10, Vascular Endothelial growth Factor (VEGF), Interferon (IFN)-γ, Monocyte Chemoattractant Protein-1(MCP-1) and Epidermal Growth Factor were assayed. Muscle necrosis was determined by hematoxylin and eosin staining of the Vastus Lateralis biopsies. <h3>Results</h3> Intramuscular TNFR1 concentrations increased over 7 days (0.83 ± 1.1 µg/L to 2.07 ± 2.65 µg/L; p = 0.042), as did intramuscular interleukin-10 (22.69 ± 26.5 ng/L to 59.8 ± 80.0 ng/L; p = 0.005). Increases in serum IL-1a (0.52 ± 0.26 ng/L to 0.57 ± 0.28 ng/L, p = 0.03), VEGF (166.86 ± 231.7 ng/L to 246.6 ± 236.7 ng/L, p &lt; 0.001) and MCP-1 (886.8 ± 685.0 ng/L to 386.49 ± 469.7 ng/L, p &lt; 0.001) were seen as well as a decrease in IL-6 (322.2 ± 422.7 ng/L to 78.55 ± 184.4 ng/L, p &lt; 0.001), il-10 (22.73 ± 51.1 ng/L to 7.61 ± 15.3 ng/L, p = 0.03), IFN- γ (4.76 ± 11.0 ng/L to 1.28 ± 2.02 ng/L, p = 0.02) and MCP-1 (886.8 ± 685.0 ng/L to 386.49 ± 469.7 ng/L, p &lt; 0.001). Neither myonecrosis nor change in RF<sub>CSA</sub> was related to that in intramuscular cytokines by linear and logistical-regression analysis, using 10% loss as a cut off. Loss in RF<sub>CSA</sub> over 10 days was very weakly correlated with serum TNFR1 concentration on days 1 (r<sup>2</sup>=0.12; p &lt; 0.01) and 7 (r<sup>2</sup>=0.09; p = 0.02) and with serum IL-10 concentration (r<sup>2</sup>=0.19; p &lt; 0.01). Myofibre necrosis was unrelated to serum cytokine profile. <h3>Discussion</h3> Soluble TNFR1 is associated with the degree of muscle wasting in critical illness. This relationship may be causal as TNF1R signalling leads to activation of nuclear factor kappa beta and apoptosis. Whilst no evidence was seen for intramuscular inflammation, increased intramuscular IL-10 may be protective, in its anti-inflammatory role.
Endosonography (EUS), EUS-guided Fine Needle Aspiration (FNA) and 18- Fluorodeoxyglucose Positron Emission Tomography (18-FDG PET) in the evaluation of Pancreatic Cystic Tumors (PCTs)
Authors: WC Lim, L McHenry, M Tann, JM DeWitt, JK Leblanc, TJ Howard, CM Schmidt, EL Fogel, S Sherman, GA Lehman
Journal: Endoscopy (2006)

Introduction: The widespread use of high quality cross-sectional abdominal imaging has dramatically increased the detection of pancreatic cystic tumors (PCTs), classified as benign, potentially malignant (PM) or malignant (M). Based on the principle of high tissue metabolism and 18-FDG uptake in M-cells, 18-FDG PET was reported to be useful in distinguishing M- from non-malignant (NM-) PCTs. Aim: To prospectively evaluate the diagnostic yield of 18-FDG PET compared to EUS and EUS-FNA in the evaluation of PCTs. Methods: Single center study. From January 2002 to November 2004, 39 patients with PCTs were prospectively evaluated: 4 patients were excluded (no histological confirmation); 35 patients (17 ♀, 18 ♂; median age 64 [35–88] yrs) were included. EUS (n=31) was performed prior to 18-FDG PET (n=35). PCTs with an associated mass were considered M by EUS. EUS-FNA cytology results were reported as negative (benign, atypical or suspicious cells) or positive (M-cells), and 18-FDG PET as low (negative) or high (positive) probability for malignancy. A cancer diagnosis was established by M-cells on EUS-FNA or surgery. The performance characteristics of EUS, EUS-FNA and 18-FDG PET in diagnosing M-PCTs were evaluated. Results: Of 35 patients with tissue diagnosis, 10 (28.6%) had cancer (1 mucinous cystadenocarcinoma, 9 M-IPMN), while 25 had NM-PCTs (5 mucinous cystadenoma, 15 IPMN, 5 pseudocysts). The sensitivity, specificity, PPV, NPV and accuracy of (a) EUS morphology were 78%, 95%, 87.5%, 91% and 90%; (b) EUS-FNA were 89%, 100%, 100%, 95% and 97%; (c) 18-FDG PET were 70%, 88%, 70%, 88% and 83% respectively (table 1). Conclusion: In this series, EUS and EUS-FNA was more accurate than 18-FDG PET in differentiating M- from NM-PCTs. Further studies are needed to assess the role of 18-FDG PET in the evaluation of PCTs before adopting it as part of the diagnostic algorithm.
NIH Wins Broad Patent on Human Gene Therapy
Authors: S. Jenks
Journal: JNCI Journal of the National Cancer Institute (1995)

Journal Article NIH Wins Broad Patent on Human Gene Therapy Get access Susan Jenks Susan Jenks Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 87, Issue 8, 19 April 1995, Pages 569–570, https://doi.org/10.1093/jnci/87.8.569 Published: 19 April 1995
Abstract 777: TAp73 depletion unleashes p53-mediated apoptotic response to lethal DNA damage.
Authors: Dongshi Chen, Lihua Ming, Fangdong Zou, Jian Yu, Lin Zhang
Journal: Cancer Research (2013)

Abstract DNA damage response is essential for maintenance of genomic integrity and functions as a guardian against oncogenic transformation. Ionizing radiation and chemotherapeutic drugs used in anticancer therapies often incur DNA damage in killing of tumor cells. The central regulator of DNA damage response is the tumor suppressor p53, which inhibits cell cycle progression by activating p21 and other cell cycle regulators, or induces apoptosis through proapoptotic targets such as PUMA and Bax. In addition to p53, other p53 family members, such as p73 and p63, also play a significant role in DNA damage response. However, it has remained unclear how coordination of different p53 family members modulates DNA damage response. In this study, we found that sub-lethal levels of DNA damage up-regulated TAp73, the transcriptionally active form of p73, whereas lethal doses of DNA damage triggered TAp73 depletion. In response to mild DNA damage, TAp73 occupied p53 responsive elements in the promoters of p53 target genes to keep the transcriptional activity of p53 in check, which resulted in cell cycle arrest. Following excessive DNA damage, the depletion of TAp73 resulted in enhanced induction of p53 target genes such as PUMA, Noxa and Bax, leading to apoptosis initiation. Furthermore, our results demonstrated that TAp73 depletion after excessive DNA damage was caused by ubiquitin/proteasome-mediated degradation of E2F1, which activates TAp73 expression to maintain cell survival. Collectively, our results suggest that modulation of p53 activity by TAp73 mediates differential responses to genotoxic stress. Citation Format: Dongshi Chen, Lihua Ming, Fangdong Zou, Jian Yu, Lin Zhang. TAp73 depletion unleashes p53-mediated apoptotic response to lethal DNA damage. [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 777. doi:10.1158/1538-7445.AM2013-777
Enhanced epidemic intelligence using a web-based screening system during the 2010 FIFA World Cup in South Africa
Authors: J Mantero, E Szegedi, L Payne Hallström, A Lenglet, E Depoortere, B Kaic, L Blumberg, J P Linge, D Coulombier
Journal: Eurosurveillance (2014)

The 2010 FIFA World Cup took place in South Africa between 11 June and 11 July 2010. The European Centre for Disease Prevention and Control (ECDC), in collaboration with the hosting authorities, carried out enhanced epidemic intelligence activities from 7 June to 16 July 2010 for timely detection and monitoring of signals of public health events with a potential to pose a risk to participants and visitors. We adapted ECDC’s routine epidemic intelligence process to targeted event-based surveillance of official and unofficial online information sources. A set of three specifically adapted alerts in the web-based screening system MedISys were set up: potential public health events in South Africa, those occurring in the participating countries and those in the rest of the world. Results were shared with national and international public health partners through daily bulletins. According to pre-established ECDC criteria for the World Cup, 21 events of potential public health relevance were identified at local and international level. Although none of the events detected were evaluated as posing a serious risk for the World Cup, we consider that the investment in targeted event-based surveillance activities during the tournament was relevant as it facilitated real-time detection and assessment of potential threats. An additional benefit was early communication of relevant information to public health partners.
AB0610 Difference in Skin Elasticity between Diffuse and Limited Systemic Sclerosis
Authors: C. Bruno, C. Tripolino, S. Mazzuca, M. Calabria, F. Ursini, S. Naty, R.D. Grembiale
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Systemic sclerosis (SSc) is a chronic autoimmune disease characterized by vascular damage and severe fibroproliferative phenotype, which affects skin and internal organs. To date, the modified Rodnan Skin Score (mRSS) is the most employed technique to assess cutaneous involvement in SSc. However, recent studies consider the employment of ultrasound elastosonography (UE), highlighting its ability to identify the reduction of strain in the skin. Currently, SSc can be classified into two different subsets: limited (LSS) and diffuse (DSS) disease. The former is usually confined to specific regions of the body, with no internal organ involvement, the latter is characterized by diffuse skin involvement, severe internal organ involvement and poor prognosis. <h3>Objectives</h3> The present study was aimed to explore possible differences in skin stiffness between LSS and DSS by using UE. <h3>Methods</h3> 20 SSc patients (10 with LSS and 10 with DSS) and 10 healthy subjects, were recruited for the present study. They underwent clinical examination and ultrasound evaluation. UE was performed at palmar surface of each finger tip. Images were obtained by applying repetitive skin compression. The elastogram, which reflects the relative elasticity of the tissues, was created as a color coded map (i.e. blue = great stiffness, red = low stiffness). Images were analyzed by a proprietary software (Esaote elastosonography module, Esaote, Inc., Italy) that allows to obtain a numeric evaluation of stiffness expressing the global percentage of hardness. "Skin stiffness" was computed by considering the average of eight fingers for each patient. <h3>Results</h3> Table 1 reports clinical and ultrasound features of SSc group and control group. As shown, mean age was 61±14 years in SSc subjects and 55±13.9 years in healthy subjects. Overall, SSc subjects showed higher skin stiffness values than control group (p&lt;0.01), whereas no difference concerning the other variables were found. Among SSc group, patients with LSS were comparable to DSS regarding age, disease duration and Raynaud9s phenomenon duration, whereas mRSS was significantly lower (p=0.01). Regarding skin stiffness, DSS subjects showed highest values when compared to both controls (p&lt;0.01) and LSS subjects (Fig. 1). <h3>Conclusions</h3> The present investigation has two main results. First, ultrasound with elastosonography seem to discriminate skin stiffening in SSc patients compared to healthy subjects, thus confirming the findings of previous investigations. Second, among SSc patients, those with DSS show a higher skin stiffness compared to LSS subjects, supporting the more severe course of DSS compared to LSS. <h3>References</h3> Iagnocco A et al (2010) J Rheumatol 37: 1688-91 Ostojić P et al (2006) Clin Rheumatol 25:453-7 <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.1280
AB0706 Centre-Related Features Determine Variability of Hospital Admissions of Patients with Spondyloarthritides in Spain
Authors: M. Andres, F. Sivera, P. Vela, S. Pérez-Vicente
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Objectives</h3> To explore the variability in hospital admissions of patients with spondyloarthritides (SpA) in Spain, and which factors related with the centre contribute to this variability (after adjustment by patient and disease features). <h3>Methods</h3> Descriptive cross-sectional study, part of the emAR II study performed in Spain in 2009-2010. Case notes of patients with a diagnosis of SpA and at least one visit in the Rheumatology units within the previous two years were selected using an equiprobabilistic sampling process and audited. Collected variables related to hospital admissions, clinical features (related to the SpA) and non-clinical features (related to the patient, the responsible physician, the Rheumatology unit and the hospital centre). Statistical analyses included a descriptive analysis and bivariate analysis to assess association between risk factors and admissions. Then those variables with a significant association in the bivariate analysis and/or deemed as clinically relevant or potential confounders, all were later included in a multilevel logistic regression analysis of random intercept with non-random slopes, in order to assess variability in hospital admissions between centres. <h3>Results</h3> A total of 1,168 patients9 case notes from 45 centres were enrolled. Main SpA forms were ankylosing spondylitis (55.2%) and psoriatic arthritis (22.2%). A total of 248 admissions of 196 patients (19.2%, n=1,020) were registered, mainly due to surgical procedures (32.7%), comorbidities (15.3%) and disease activity (12.1%). A variability of 17.6% in hospitalizations between centres was noted (Table), not explained by clinical variables (M2[A1]). This variability was attributed to hospital-related factors (M3): the number of admissions of the centre (OR 1.003, 95%CI 1.000-1.006), the existence of computer-assisted admission orders (OR 3.754, 95%CI 1.201-11.731) and the availability of ultrasound in the unit (OR 0.400, 95%CI 0.211-0.757) showed a significant association with admissions, but explained 42.9% of the variability. The risk of a patient with SpA of being hospitalized was found to double (median OR 2.086) depending on the hospital where the patient is being managed. <h3>Conclusions</h3> Hospital admissions of patients with SpA varied widely between hospitals, in relation with centre characteristics. Further studies are needed to ascertain which specific factors are causing the variation between centres, as variables included in this study explained less than half of the variability. <h3>Acknowledgements</h3> To César Hernández, Loreto Carmona, María Jesús García de Yébenes, Miguel Άngel Descalzo, Juan Manuel Barrio, María Auxiliadora Martín and Estíbaliz Loza, for their significant contribution in the development of the study protocol, electronic database and statistical analysis. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.1693