tbuckley/cabot-search huggingface dataset:
Abstract 3835: DNA methylation levels in mononuclear DNA in breast cancer from the New York site of the BCFR
Authors: Hui-Chen Wu, Qiao Wang, Regina M. Santella, Mary B. Terry
Journal: Cancer Research (2015)

Abstract Alterations in DNA methylation both at specific loci and overall, have been associated with breast cancer. These alterations have primarily been observed at the tissue level, although emerging studies are evaluating white blood cell (WBC) DNA methylation. To examine whether DNA methylation change measured prospectively in a family-based cohort are associated with breast cancer risk, we measured methylation levels of two repetitive elements (LINE-1, and Sat2) and three genes in mononuclear cell DNA (BLNK, CUEDC1, and IBSP) previously identified as differentially methylated in breast cancer in a genome-wide association study. After an average of 8 years of followup, we observed 81 invasive incident breast cancers and compared their methylation levels measured with baseline bloods with the remaining 1,508 women not affected with breast cancer in the New York site of the Breast Cancer Family Registry (BCFR). We found that the overall percent methylation in CUEDC1 was statistically significantly higher in breast cancer cases than in controls (78.0% versus 76.8%, respectively, p = 0.02). In a multivariable Cox Proportional Hazards model adjusting for age at blood draw, with each 1 unit increase in CUEDC1 methylation level, the OR for breast cancer increased by 1.07 (95% Confidence Interval (CI) = 1.00-1.14). We did not find the other methylation markers to be related to risk. The area under the curve was 67.6% (95% CI = 61.4% to 73.8%) for the 5 methylation markers and Gail risk score, compared with 63.3% for the Gail score only. Our finding for CUEDC1 replicates the finding from the Sisters Study supporting that selected markers selected markers of epigenetic changes measured in WBC may be potential biomarkers of breast cancer risk. Citation Format: Hui-Chen Wu, Qiao Wang, Regina M. Santella, Mary B. Terry. DNA methylation levels in mononuclear DNA in breast cancer from the New York site of the BCFR. [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 3835. doi:10.1158/1538-7445.AM2015-3835
Resurgence of Progressive Massive Fibrosis in Coal Miners — Eastern Kentucky, 2016
Authors: David J. Blackley, James B. Crum, Cara N. Halldin, Eileen Storey, A. Scott Laney
Journal: MMWR Morbidity and Mortality Weekly Report (2016)

Coal workers' pneumoconiosis, also known as "black lung disease," is an occupational lung disease caused by overexposure to respirable coal mine dust. Inhaled dust leads to inflammation and fibrosis in the lungs, and coal workers' pneumoconiosis can be a debilitating disease. The Federal Coal Mine Health and Safety Act of 1969 (Coal Act),* amended in 1977, established dust limits for U.S. coal mines and created the National Institute for Occupational Safety and Health (NIOSH)-administered Coal Workers' Health Surveillance Program with the goal of reducing the incidence of coal workers' pneumoconiosis and eliminating its most severe form, progressive massive fibrosis (PMF),† which can be lethal. The prevalence of PMF fell sharply after implementation of the Coal Act and reached historic lows in the 1990s, with 31 unique cases identified by the Coal Workers' Health Surveillance Program during 1990-1999. Since then, a resurgence of the disease has occurred, notably in central Appalachia (Figure 1) (1,2). This report describes a cluster of 60 cases of PMF identified in current and former coal miners at a single eastern Kentucky radiology practice during January 2015-August 2016. This cluster was not discovered through the national surveillance program. This ongoing outbreak highlights an urgent need for effective dust control in coal mines to prevent coal workers' pneumoconiosis, and for improved surveillance to promptly identify the early stages of the disease and stop its progression to PMF.
Upregulation of Osteoactivin Upon Exposure to Tyrosine Kinase Inhibitors Impairs the T Cell Stimulatory Capacity of Monocyte-Derived Dendritic Cells
Authors: Michael Gutknecht, Lisa Güttler, Mark-Alexander Schwarzbich, Julia Salih, Lothar Kanz, Helmut R. Salih, Susanne Malaika Rittig, Frank Grünebach
Journal: Blood (2011)
Calculating acute:chronic workload ratios using exponentially weighted moving averages provides a more sensitive indicator of injury likelihood than rolling averages
Authors: Nicholas B Murray, Tim J Gabbett, Andrew D Townshend, Peter Blanch
Journal: British Journal of Sports Medicine (2016)

Objective To determine if any differences exist between the rolling averages and exponentially weighted moving averages (EWMA) models of acute:chronic workload ratio (ACWR) calculation and subsequent injury risk. Methods A cohort of 59 elite Australian football players from 1 club participated in this 2-year study. Global positioning system (GPS) technology was used to quantify external workloads of players, and non-contact ‘time-loss’ injuries were recorded. The ACWR were calculated for a range of variables using 2 models: (1) rolling averages, and (2) EWMA. Logistic regression models were used to assess both the likelihood of sustaining an injury and the difference in injury likelihood between models. Results There were significant differences in the ACWR values between models for moderate (ACWR 1.0–1.49; p=0.021), high (ACWR 1.50–1.99; p=0.012) and very high (ACWR &gt;2.0; p=0.001) ACWR ranges. Although both models demonstrated significant (p&lt;0.05) associations between a very high ACWR (ie, &gt;2.0) and an increase in injury risk for total distance ((relative risk, RR)=6.52–21.28) and high-speed distance (RR=5.87–13.43), the EWMA model was more sensitive for detecting this increased risk. The variance (R 2 ) in injury explained by each ACWR model was significantly (p&lt;0.05) greater using the EWMA model. Conclusions These findings demonstrate that large spikes in workload are associated with an increased injury risk using both models, although the EWMA model is more sensitive to detect increases in injury risk with higher ACWR.
Abstract 4631: AKAP12 is elevated in paclitaxel-resistant ovarian cancer cells and correlates with poor ovarian cancer patient survival
Authors: Nicholas Bateman, Elizabeth Jaworski, Guisong Wang, Elizabeth Dubil, Charlotte Marcus, Kelly Conrads, Pang-ning Teng, Brian Hood, Chad Hamilton, Larry Maxwell, Kathleen Darcy, Thomas Conrads
Journal: Cancer Research (2015)

Abstract Objective: Although most ovarian cancer patients respond initially to the standard of care involving carboplatinum/paclitaxel-based chemotherapy, the majority will recur with chemotherapeutically resistant disease. Unfortunately, no clinical biomarker(s) for predicting or monitoring chemotherapeutic resistance are available. We sought to identify shed and/or secreted proteins from paclitaxel-resistant human ovarian cancer cells and identify whether any of these correlate with ovarian cancer patient outcome. Methods: A proteomic analysis of secretomes from high grade serous ovarian cancer (HGSOC) cells (OV90) was compared to that from a syngeneic paclitaxel-resistant variant (OV90-TR) and a cancer cell line developed from a chemorefractory HGSOC patient. Associations between the identified candidates and patient outcome were assessed from publicly available transcript expression data (n = 545 ovarian cancer patients) and validated independently (n = 795 ovarian cancer patients). Results: Among the 81 differentially abundant proteins identified (q&amp;lt;0.05) from paclitaxel-sensitive vs -resistant HGSOC cell secretomes, AKAP12 was verified to be elevated at the protein and transcript level in all models of paclitaxel-resistant HGSOC. Further, elevated AKAP12 transcript expression was found to significantly correlate with poor progression-free (Hazard Ratio = 1.487 (± 0.148), p = 0.0085 (± 0.002) and overall (Hazard Ratio = 1.22 (± 0.08), p = 0.009 (± 0.013) survival. Conclusions: These findings suggest that elevation and efflux of AKAP12 is characteristic of paclitaxel-resistant HGSOC cells and that elevated AKAP12 expression correlates with poor ovarian cancer patient survival. Citation Format: Nicholas Bateman, Elizabeth Jaworski, Guisong Wang, Elizabeth Dubil, Charlotte Marcus, Kelly Conrads, Pang-ning Teng, Brian Hood, Chad Hamilton, Larry Maxwell, Kathleen Darcy, Thomas Conrads. AKAP12 is elevated in paclitaxel-resistant ovarian cancer cells and correlates with poor ovarian cancer patient survival. [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 4631. doi:10.1158/1538-7445.AM2015-4631
Interim Analysis of a Phase II Study of Denileukin Diftitox (Ontak) for Relapsed/Refractory T-Cell Non-Hodgkin’s Lymphoma.
Authors: Nam H. Dang, Barbara Pro, Fredrick B. Hagemeister, Dan Jones, Barry Samuels, Maria A. Rodriguez, Andre Goy, Jorge E. Romaguera, Pamela L. Walker, Larry Kwak, Luis Fayad
Journal: Blood (2004)
Delayed Hepatitis B Active Viral Replications without Active Viral Biochemical Hepatitis Two Months after Cessation of Pre-Emptive Adefovir Therapy in a Patient with Waldenstrom Macroglobulinemia Treated with Rituximab and Fludarabine Chemotherapy.
Authors: Amr S. Hanbali, Yasser Khaled
Journal: Blood (2005)
A T2* MRI Prospective Survey on Heart and Liver Iron In Thalassemia Major Patients Treated with Sequential Deferiprone–Desferrioxamine versus Deferiprone and Desferrioxamine In Monotherapy
Authors: Alessia Pepe, Giuseppe Rossi, Antonella Meloni, Maria Chiara Dell'Amico, Luciano Prossomariti, Domenico Giuseppe D'Ascola, Aldo Filosa, Pasquale Pepe, Vincenzo Positano, Claudio Ascioti, Alma Lippi, Massimo Lombardi, Marcello Capra
Journal: Blood (2010)
Growth factor receptor binding protein 14 inhibition triggers insulin‐induced mouse hepatocyte proliferation and is associated with hepatocellular carcinoma
Authors: Lucille Morzyglod, Michèle Caüzac, Lucie Popineau, Pierre‐Damien Denechaud, Lluis Fajas, Bruno Ragazzon, Véronique Fauveau, Julien Planchais, Mireille Vasseur‐Cognet, Laetitia Fartoux, Olivier Scatton, Olivier Rosmorduc, Sandra Guilmeau, Catherine Postic, Chantal Desdouets, Christèle Desbois‐Mouthon, Anne‐Françoise Burnol
Journal: Hepatology (2016)

Metabolic diseases such as obesity and type 2 diabetes are recognized as independent risk factors for hepatocellular carcinoma (HCC). Hyperinsulinemia, a hallmark of these pathologies, is suspected to be involved in HCC development. The molecular adapter growth factor receptor binding protein 14 (Grb14) is an inhibitor of insulin receptor catalytic activity, highly expressed in the liver. To study its involvement in hepatocyte proliferation, we specifically inhibited its liver expression using a short hairpin RNA strategy in mice. Enhanced insulin signaling upon Grb14 inhibition was accompanied by a transient induction of S-phase entrance by quiescent hepatocytes, indicating that Grb14 is a potent repressor of cell division. The proliferation of Grb14-deficient hepatocytes was cell-autonomous as it was also observed in primary cell cultures. Combined Grb14 down-regulation and insulin signaling blockade using pharmacological approaches as well as genetic mouse models demonstrated that Grb14 inhibition-mediated hepatocyte division involved insulin receptor activation and was mediated by the mechanistic target of rapamycin complex 1-S6K pathway and the transcription factor E2F1. In order to determine a potential dysregulation in GRB14 gene expression in human pathophysiology, a collection of 85 human HCCs was investigated. This revealed a highly significant and frequent decrease in GRB14 expression in hepatic tumors when compared to adjacent nontumoral parenchyma, with 60% of the tumors exhibiting a reduced Grb14 mRNA level.Our study establishes Grb14 as a physiological repressor of insulin mitogenic action in the liver and further supports that dysregulation of insulin signaling is associated with HCC. (Hepatology 2017;65:1352-1368).
OC-022 Multicentre comparison of the Glasgow Blatchford and Rockall scores in the prediction of clinical endpoints in upper gastrointestinal haemorrhage
Authors: A J Stanley, H Dalton, O Blatchford, D Ashley, C Mowat, A Cahill, D R Gaya, U Warshow, E Thompson, M Groome, G Benson, W Murray
Journal: Gut (2010)

<h3>Introduction</h3> The pre-endoscopic Glasgow Blatchford Score (GBS) can identify low-risk patients with upper gastrointestinal haemorrhage (UGIH) who may be suitable for out-patient management. Although it does not include the patient9s age, the GBS appears to have high accuracy in predicting clinically relevant endpoints. Our aim was to compare the GBS with both the pre-endoscopy (admission) and post-endoscopy (full) Rockall scores in predicting need for clinical intervention and mortality. <h3>Methods</h3> Data on consecutive patients presenting to four UK hospitals (Glasgow Royal Infirmary, Royal Cornwall Hospital Truro, University Hospital of North Tees and Ninewells Hospital Dundee) were collected. Admission history, clinical and laboratory data, endoscopic findings and treatment, and clinical follow-up were recorded. We used ROC curves to compare the three scores in the separate prediction of death, endoscopic or surgical intervention and transfusion. <h3>Results</h3> 1556 patients (mean age 56.7 years; 62% male) presented with UGIH to the four hospitals during the study period. 74 (4.8%) died, 223 (14.3%) had endoscopic or surgical intervention and 363 (23.3%) required transfusion. The GBS was equally effective at predicting death compared with both the admission Rockall score (area under ROC curve 0.804 vs 0.801) and the full Rockall score (AUROC 0.741 vs 0.790). In predicting endo/surgical intervention, the GBS was superior to the admission Rockall score (AUROC 0.858 vs 0.705, p&lt;0.00005) but similar to the full Rockall score (AUROC 0.822 vs 0.797). The GBS was superior to both the admission Rockall (AUROC 0.944 vs 0.756, p&lt;0.00005) and the full Rockall score (AUROC 0.935 vs 0.792, p&lt;0.00005) in predicting need for transfusion. <h3>Conclusion</h3> Despite not incorporating age, the GBS is as effective as the admission and full Rockall scores in predicting death after UGIH. It is superior to both the admission and full Rockall scores in predicting need for transfusion and superior to the admission Rockall score in predicting endoscopic or surgical intervention.
In vivo visualization of endogenous miR-21 using hyaluronic acid-coated graphene oxide for targeted cancer therapy
Authors: Do Won Hwang, Han Young Kim, Fangyuan Li, Ji Yong Park, Dohyun Kim, Jae Hyung Park, Hwa Seung Han, Jung Woo Byun, Yun-Sang Lee, Jae Min Jeong, Kookheon Char, Dong Soo Lee
Journal: Biomaterials (2016)
Detection of the Malignant B Cell Clone in Multiple Myeloma Via High Throughput Sequencing Is Robust to Significant Levels of Somatic Hypermutation
Authors: Christopher S Carlson, Alfred L. Garfall, Wenzhao Meng, Robert Daber, Bochao Zhang, Uri Hershberg, Adam D. Cohen, Dan T. Vogl, Weiss Brendan, Martin Carroll, Edward A. Stadtmauer, Eline Luning Prak
Journal: Blood (2014)
Abstract 2736: Analysis of ROS concentration in serous ovarian carcinoma
Authors: Shakeria L. Cohen, Sharifeh Mehbari, Edward E. Partridge, Felix Aikhionbare
Journal: Cancer Research (2015)

Abstract Serous ovarian cancer is the most malignant form of cancer affecting the female reproductive tract. Early detection is associated with 90% five year survival however, current screening tools are not sensitive enough to detect ovarian cancer at early stages. Thus, there remains a critical need for advanced diagnositic tools for early detection and improved prognosis. An accumulation of ROS compounds coupled with increased oxidative stress over time can be deleterious and has been implicated in many human diseases including serous ovarian cancer. Evalution of the ROS concentration in different stages of serous ovarian cancer could be helpful in understanding of the different signaling pathways that may be involved in the transformations of ovarian tumor tissue phenotype. In this study the production of ROS compounds were evaluated in the mitochondria as a caustic of oxidative stress that involve in the transformations of serous ovarian carcinoma. Through the use of a fluorogenic probe, dichlorodihydrofluorescin (DCFH-DiOxyQ) that reacts with the free radicals in a sample, cumulative level of ROS concentrations among stages of serous ovarian carcinoma were detected. Results revealed an increase of 25% ROS fluorescence in the malignant stages compared to normal/surrounding tissues samples. Additionally there was a notably higher ROS concentration in the malignant stages compared to the borderline tissue samples. Results from this study indicate an exponential increase in the levels of ROS from the benign to malignant stages of the disease, suggesting that cumulative ROS levels from early to late of stages may be involved in the progressive stages of the serous ovarian disease type. Citation Format: Shakeria L. Cohen, Sharifeh Mehbari, Edward E. Partridge, Felix Aikhionbare. Analysis of ROS concentration in serous ovarian carcinoma. [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 2736. doi:10.1158/1538-7445.AM2015-2736
A new symptom measure in chronic myeloid leukemia.
Authors: L. A. Williams, A. Garcia-Gonzalez, P. Ault, T. R. Mendoza, C. S. Cleeland, G. M. Mobley, J. L. Williams, J. E. Cortes
Journal: Journal of Clinical Oncology (2011)

e19545 Background: A major barrier to effective symptom management in chronic myeloid leukemia (CML) is inadequate assessment. We aimed to develop a short, easily-understood, valid, and reliable patient-reported outcome measure of CML symptoms for research and practice. Methods: 127 patients with CML completed the 13 symptom severity and 6 interference items of the core M. D. Anderson Symptom Inventory (MDASI) plus 7 CML-specific symptom items (Table), generated from patient and expert input, measured on a 0-10 scale (0 = none, 10 = worst imaginable). 85 patients completed the same items 2 weeks later. Patients also answered a single quality-of-life (QOL) question. Demographic and disease information was collected on all patients. Multivariate analysis examined relationships among items. Psychometric procedures determined reliability and validity of the MDASI-CML. Results: Sample characteristics and symptom severity and interference are in the table. All items were retained as clinically significant and nonredundant. The reliability index (Cronbach α) and test-retest reliability of the 20 symptom items were 0.94 and 0.93 respectively and of the 6 interference items were 0.94 and 0.91 respectively. The MDASI-CML discriminated between patients who were employed versus those medically disabled and with good versus poor QOL. Symptom severity explained 87% of the variance in interference, with the core symptoms explaining 83% and the CML-specific symptoms explaining 76%. Conclusions: We have validated an analytic tool, the MDASI-CML, for quantifying CML symptoms. The MDASI-CML is being used to assess side effects in treatment trials and to monitor symptoms in clinical care. Sample characteristics and symptom means. Number % of sample Female 68 54 White 97 76 Employed 79 62 Performance status < 2 127 99 Chronic phase 124 98 Receiving kinase inhibitor therapy 119 94 Imatinib 57 48* Dasatinib 32 28* Nilotinib 19 16* Investigational 11 9* Mean Standard deviation Age, years 50.4 13.7 All symptom items 1.5 1.4 Core symptom items 1.6 1.5 CML symptom items 1.5 1. Diarrhea 1.0 1.7 Swelling 1.7 2.1 Rash/skin changes 1.3 1.8 Cramping 2.4 2.4 Malaise 1.9 2.4 Bruising/bleeding 1.1 1.6 Headache 1.3 1.9 Interference items 1.5 1.9 QOL rating (10 = best) 8.2 1.9 *% total receiving KIs
Abstract 2288: Lipoprotein(a) and vitamin C affect the development of breast cancer tumors in Lp(a)+; Gulo-/- mice
Authors: John Cha, M. Waheed Roomi, Aleksandra Niedzwiecki, Matthias Rath
Journal: Cancer Research (2015)

Abstract Lipoprotein(a), composed of LDL and an adhesive protein apo(a), is produced in humans and primates, the species which lost an ability to synthesize vitamin C endogenously. We have shown earlier that Lp(a), due to its strong ECM binding properties, may be considered a biological ‘stability’ molecule for the structurally weakened connective tissue in the vascular wall. The development and progression of cancer is characterized by loss of ECM integrity which facilitates tumor growth and metastasis. We developed a unique mouse model lacking endogenous vitamin C production (Gulo-/-) and synthesizing human Lp(a) (lp(a)+), which has been used in this study to investigate the role of Lp(a) and other lipoproteins in cancer. The female Gulo-/-:Lp(a)+ and control wild type Balb/c mice were orthotopically inoculated with 4T1 breast cancer cells (500,000) The transgenic and control mice were divided into 4 different dietary groups in respect to dietary vitamin C intake: A) low ascorbate intake for 6 weeks; B) high ascorbate intake for 6 weeks; C) low ascorbate intake for 3 weeks followed by high ascorbate for 3 weeks; D)high ascorbate intake for 3 weeks followed by low ascorbate for 3 weeks. Control groups of Lp(a)+;Gulo(-/-) mice without tumor inoculation were put on the same Vitamin C regimens. Wild type controls included mice without and with 4T1 inoculation kept on regular mouse chow for 6 weeks. After 6 weeks all (100%) wild type mice developed tumors, while 50% of Lp(a)+;Gulo(-/-) mice kept on high ascorbate diet for 6 weeks did not develop primary tumors and in only a small number of mice some residual tumor cells or inflammatory infiltrates were detected in the lungs by histology. In transgenic mice supplemented with low vitamin C for 6 weeks, the reduction of primary tumors incidence was 33% compared to wild type mice. In addition, primary tumors from wild type mice were on average over 2-fold larger (1.80+/-0.62g) than tumors from Lp(a)+;Gulo(-/-) mice on continual low Vitamin C (0.77+/-0.98g) or continual high Vitamin C (0.63+/-1.09g. Primary tumors from Lp(a)+;Gulo(-/-) mice immunostained positively for Lp(a) and their size was inversely proportional Lp(a) cholesterol serum levels. Lp(a) could not be detected in tumors from wild type mice and the presence of tumors was associated with higher LDL serum levels. The results implicate that Lp(a) may play a role in controlling tumor growth and expansion through its ECM adhesive properties. Citation Format: John Cha, M. Waheed Roomi, Aleksandra Niedzwiecki, Matthias Rath. Lipoprotein(a) and vitamin C affect the development of breast cancer tumors in Lp(a)+; Gulo-/- mice. [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 2288. doi:10.1158/1538-7445.AM2015-2288
Assessment of CEBPA Mutations Might Contribute to a Better Prognostic Assignment in Patients with Intermediate-Risk Cytogenetics Acute Myeloid Leukemia (AML).
Authors: Marta Pratcorona, Montserrat Torrebadell, Neus Villamor, Maria Rozman, Mireia Camós, Ana Carrió, Dolors Costa, Marina Díaz Beyáa, Emili Montserrat, Jordi Esteve
Journal: Blood (2009)
Epigenetic Status Of CEBPA Promoter and Expression Of CEBPα Correlates With Molecular Genetic Subtype and CD2 Aberrant Expression In B Cell Precursor ALL
Authors: Lucie Slamova, Julia Starkova, Karel Fiser, Eva Fronkova, Leona Rezkova Reznickova, Marketa Kubricanova Zaliova, Kamila Polgarova, Jan Stary, Jan Trka, Ondrej Hrusak, Ester Mejstrikova
Journal: Blood (2013)