tbuckley/cabot-search huggingface dataset:
Abstract 2154: ERK/MAPK pathway inhibits tumorigenesis and cellular reprogramming of pancreatic cancer cells
Authors: Benjamin le Calvé, Xavier Deschenes-Ximard, Filippos Kottakis, Véronique Bourdeau, Frédéric Lessard, Karine Moineau-Vallée, Emmanuelle Saint-Germain, Julien Fitamant, Rushika Miriam Perera, Nabeel Bardeesy, Gerardo Ferbeyre
Journal: Cancer Research (2015)

Abstract Reprogrammation of cancer cells into stem-like state is one the most important mechanisms implicated in tumor initiation, metastasis and resistance to chemotherapies. Acquisition of stem-like cell property is directly correlated with the level of activation of the ERK/MAPK pathway. Our study focuses on the implication of the downregulation of this pathway during the transition of pancreatic benign neoplasms to pancreatic ductal adenocarcinoma. This transformation is directly correlated with the acquisition of stem-like cells properties. Conversely, hyperactivation of the ERK pathway using phosphatase inhibitors abrogates the stem-like cell phenotype. We analyzed the variation of genes expression by microarrays analysis between cells obtained from pancreatic intraepithelial neoplasias and pancreatic cancer. These analyses implicate the expression of DUSPs and genes related to stem cell biology in tumor progression during pancreatic cancer. Citation Format: Benjamin le Calvé, Xavier Deschenes-Ximard, Filippos Kottakis, Véronique Bourdeau, Frédéric Lessard, Karine Moineau-Vallée, Emmanuelle Saint-Germain, Julien Fitamant, Rushika Miriam Perera, Nabeel Bardeesy, Gerardo Ferbeyre. ERK/MAPK pathway inhibits tumorigenesis and cellular reprogramming of pancreatic cancer cells. [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 2154. doi:10.1158/1538-7445.AM2015-2154
Abstract 1146: Global profiling of SPARC-regulated metabolic pathways in ovarian cancer
Authors: Sherine Taylor, Christian Sanchez, Amna Adrees, Hale Nur Ozbek, Harjapjit Sahni, Neveen A. Said
Journal: Cancer Research (2015)

Abstract We have previously reported the tumor suppressor effect of SPARC in ovarian cancer through inhibiting cancer cell growth and their interactions within the peritoneal milieu. In the present study, we sought to determine the effect of SPARC on metabolic perturbations associated with ovarian cancer using a syngeneic murine ovarian cancer model in SPARC knockout (KO) mice and their wildtype (WT) counterparts. Murine ID8 ovarian cancer cell line were injected intraperitoneally in SPARC KO and WT mice. Matched intraperitoneal tumor tissue, and ascitic fluid were harvested 6 weeks post-injection of ID8 cells and were subjected to global biochemical metabolomic profiling. In tandem, WT and KO tumors were dissected by LCM-microdissected and were subjected to gene expression profiling. Metabolomic profiling of SPARC KO tumors and ascites revealed significantly altered metabolites associated with glucose, energy, amino acid, and lipid metabolism, as well as redox homeostasis. Integrated transcriptome and metabolome analysis of the top significantly upregulated genes and metabolites in the KO compared to WT tumors and ascitic fluid revealed that the major pathways upregulated in absence of SPARC are those involved in: conversion of glucose to acetyl CoA and entry into the citric acid (TCA) cycle, respiratory electron transport and oxidative phosphorylation (SUCLG2; NDUFAB1; ATP5F1; UQCRH; ATP5H; COX5B; NDUFV1; ATP5O; IDH3B/ succinate, fumarate and pyruvate), protein metabolism (EIF5A; PREB; EIF4H; DAD1; STT3A; RPL4; SUMO1; CCT4; CCT2; IGFBP5; HSPA5; EIF3A; EIF4B; RPS19; EIF3E/ mannose; N-acetylneuraminate; N-glycolylneuraminate; glutamate; spermidine), fatty acid beta oxidation (HADH; TPI1; LPL/glycerol), purine nucleotides de novo biosynthesis and salvage (ATP5F1; ATP5H; PAICS; ATP6V1G1/ aspartate; glycine; glutamate; fumarate). Together, these data provide novel insight on the molecular mechanisms of the SPARC-induced metabolic perturbation associated with ovarian cancer that can be translated into diagnostic and prognostic biomarkers of the disease. Citation Format: Sherine Taylor, Christian Sanchez, Amna Adrees, Hale Nur Ozbek, Harjapjit Sahni, Neveen A. Said. Global profiling of SPARC-regulated metabolic pathways in ovarian 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 1146. doi:10.1158/1538-7445.AM2015-1146
OC-043 Outcomes of the Bowel Cancer Screening Programme in England after the first 1 million tests
Authors: R F Logan, J Patnick, L Coleman, C Nickerson
Journal: Gut (2010)

<h3>Introduction</h3> The Bowel Cancer Screening Programme (BCSP) in England was started in 2006 with the aim of full roll out across England by December 2009. Subjects aged 60–69 are being invited to complete three guaiac faecal occult blood tests (6 windows) every 2 years. Those with 5–6 positive windows on the first test or 1–4 positive windows on the first test but 1 or more positive on 2 further tests are referred for colonoscopy or other definitive investigation. The Programme aims to reduce the mortality from colorectal cancer by 16% in those invited for screening. <h3>Methods</h3> There is a national IT system with all patients eligible for screening in the National Health Service (NHS) in England on one database. The system is populated from NHS registration data which cover about 98% of the population of England. Call and recall is managed and data are collected via this system. Data can be analysed by local screening centre, by 5 regional hubs and at a national level. This analysis is only of subjects invited to participate in the first (prevalent) round of screening. <h3>Results</h3> By October 2008 2.1 million kits despatched had been returned by 49.6% of men and 54.4% of women invited. Uptake was lower in London (40%) but in the rest of England uptake ranged between 55–60% across the other 4 regional hubs. Of the 1.08 million returning tests 2.5% of men and 1.5% of women had a positive test. 17 518 (10 608 M, 6910 F) underwent investigation (98% had a colonoscopy as the first investigation performed). Cancer (n=1770) and advanced adenomas (n=6543) were found in 11.6% and 43% of men and 7.8% and 29% of women, respectively, investigated. 71% of cancers were “early” (10% polyp cancer, 30% Dukes A, 30% Dukes B) and 77% were left-sided (29% rectal, 45% sigmoid) with only 15% being right-sided compared with expected figures of 67% and 24% for left and right side from UK cancer registration. <h3>Conclusion</h3> In this prevalent round of screening uptake of the BCSP and FOB test positivity is in line with that from the pilot and the Nottingham and Funen trials.12 Although there was the anticipated improvement in cancer stage at diagnosis the proportion with left sided cancers is significantly higher than expected. Nevertheless these early results indicate that the anticipated reduction in mortality will be achieved.
S12 Plasma syndecan-1 level as a predictive marker of vasoplegia associated with surgery requiring cardiopulmonary bypass and possible involvement of oxidative stress
Authors: MG Rasiah, C Michaeloudes, T Svermova, Z Nikolakopoulou, B Creagh-Brown, PK Bhavsar, A Burke-Gaffney
Journal: Thorax (2016)

<h3>Background</h3> Vasoplegic syndrome (severe refractory hypotension) is associated with oxidative stress leading to endothelial dysfunction and complicates 10 to 40% of surgery requiring cardiopulmonary bypass (CPB). Whilst operative mortality is low, recovery is often prolonged in patients developing vasoplegia. There are, as yet, no validated biomarkers for vasoplegia that could be used to identify ‘at risk’ patients. We hypothesised that plasma levels of the endothelial surface layer (glycocalyx) protein, syndecan-1, shed during CPB, will be higher in patients who develop vasoplegia and that leukocyte responses to oxidative stress will be altered. <h3>Methods</h3> Patients (n = 48) undergoing cardiac surgery requiring CPB were, prospectively, enrolled; blood collected and indices of outcome recorded. A surrogate index of vasoplegia was adopted: requirement for infusion of vasoconstrictor agents for longer than 48h. An enzyme-linked immunosorbent assay was used to measure plasma levels of syndecan-1 at four time-points: after induction of anaesthesia but before CPB (T1); within 30 min of CPB ending (T2); 2h (T3) and 24h (T4) post-CPB. Real time qPCR was used to determine, in patient leukocytes (n = 20), relative expression (to house-keeping gene18<i>S</i>) of mRNA for markers of oxidative stress; NQO1 and SOD2, cytoplasmic and mitochondrial enzymes, respectively; and for comparison, TNFα. <h3>Results</h3> Syndecan-1 levels at T2 were significantly higher in vasoplegic patients (110.7 ng/mL, IQR 65.46–155.2) than non-vasoplegic patients (53.8 ng/mL, IQR 40.67–102.2; p &lt; 0.001). ROC curve analysis showed syndecan-1 had significant (p = 0.009) predictive power for onset of vasoplegia, with an area under the curve of 0.766 (95% CI: 0.6019–0.9301); and a cut-off of 63.33 ng/mL (83.33% sensitivity, 69.23% specificity). Syndecan-1 levels were higher in patients whose intensive care unit length of stay (LOS) and hospital LOS were above corresponding medians for the cohort (p = 0.0061 and p = 0.0148, respectively). NQO1 relative expression was significantly higher (p = 0.022) in vasoplegic patients (3.779 ± 1.036) than non-vasoplegic patients (1.3 ± 0.302); whereas, neither SOD2 nor TNFα expression were significantly altered. <h3>Conclusion</h3> Plasma syndecan-1 measured immediately post-CPB had good predictive power for patients at risk of vasoplegia. Greater relative expression of leukocyte NQO1 in vasoplegic patients indicates activation of antioxidant defence mechanisms in response to oxidative stress, which could contribute to syndecan-1 shedding.
The prevalence of metabolic risk factors in black men with prostate cancer undergoing consideration for androgen-deprivation therapy.
Authors: O. Gunnarsson, S. Basaria, G. Gignac
Journal: Journal of Clinical Oncology (2011)

e15082 Background: Androgen deprivation therapy (ADT) for prostate cancer (PCa) is associated with endocrine complications such as osteoporosis, weight gain, diabetes and dyslipidemia. However, in previous studies, the patient population has been predominantly white. The aim of this study was to examine relevant baseline characteristics, associated with the above-mentioned complications, in a predominantly black population presenting with prostate cancer for consideration of ADT. The information gained will help us to further risk stratify this population in regards to the possible complications of ADT. Methods: A chart-based retrospective review was conducted on all patients diagnosed with PCa presenting to one provider in an urban hospital between September 2007 and July 2010 who were being considered for ADT. Baseline data were collected on body mass index (BMI), Vitamin-D status, bone mineral density (BMD), lipid profile and diabetes status. Overweight and obesity were classified as BMI≥25 and BMI≥30, respectively, Vitamin-D sufficiency as ≥30 ng/ml, osteopenia as T scores between -1 to -2.5 and osteoporosis as T scores ≤ -2.5. Results: A total of 180 patients had sufficient data of which 71.1%, (n=128 patients, mean age 68.0 years; range 45-93) were black. Their origin was from 16 countries with 44.9 % being African Americans and 55.1% immigrants. At baseline, average BMI was 28.1±5.9 SD (range 15.4-58.5; n=104) with 42.3% of patients being overweight and an additional 31.7% obese. Mean Vitamin-D levels were 21.1±9.7 SD (range 4.0-48.0; n=93) and 80.7% of patients were Vitamin-D insufficient. Osteopenia and osteoporosis were present in 46.8% and 6.4%, respectively. Dyslipidemia was present in 40.6% of patients and 28.1% had diabetes. Conclusions: A large proportion of black men with PCa presenting for consideration of ADT are either overweight or obese at baseline. The prevalence of Vitamin-D insufficiency, low BMD, dyslipidemia and diabetes is also remarkably high. These data should be helpful for physicians considering ADT in this population.
Abstract 1998: A novel luminescent system for monitoring intracellular protein:protein interactions
Authors: Brock Binkowski, Andrew S. Dixon, Marie K. Schwinn, Mary P. Hall, Kris Zimmerman, Paul Otto, Thomas Lubben, Braeden Butler, Thomas Kirkland, Monika G. Wood, Lance P. Encell, Frank Fan, Keith V. Wood
Journal: Cancer Research (2015)

Abstract Protein:protein interactions (PPIs) are essential to the cellular signal transduction pathways that contribute to cancer. Although numerous approaches exist to monitor protein:protein interactions in vitro, methods for intracellular detection have been more limited. We developed a system for the detection of PPIs based on NanoLuc luciferase. Proteins are fused to either an 18 kDa or 1 kDa subunit. PPI facilitates interaction of the subunits, leading to increased luminescence. Intracellular PPIs are measured using a non-lytic assay protocol by providing a cell permeable substrate. The interaction status can be monitored at a single time point or followed continuously over 1-2 hours. Unlike related approaches where a luciferase enzyme is simply split, the subunits of this system were optimized for structural stability and minimal binding affinity. The result is a luminescence signal that is orders of magnitude brighter than approaches using split luciferase, allowing use of fusion protein expression levels at or near physiological levels. The low affinity interaction between subunits (Kd ∼200 μM) minimizes assay background by preventing non-specific association, and the system shows rapid reversibility using model systems such as protein kinase A catalytic and regulatory subunits. We have successfully applied this system to several PPIs related to cancer research, including TP53:MDM2, MYC:MAX, and members of the RAS-RAF signaling pathway. Citation Format: Brock Binkowski, Andrew S. Dixon, Marie K. Schwinn, Mary P. Hall, Kris Zimmerman, Paul Otto, Thomas Lubben, Braeden Butler, Thomas Kirkland, Monika G. Wood, Lance P. Encell, Frank Fan, Keith V. Wood. A novel luminescent system for monitoring intracellular protein:protein interactions. [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 1998. doi:10.1158/1538-7445.AM2015-1998
Neonatal Alloimmune Neutropenia Due to Maternal Alloimmunization Against Human Neutrophil Alloantigen-1 and -3
Authors: Larissa Barbosa Lopes, Samira Ali Abbas, Elyse Moritz, Akemi Kuroda Chiba, Dante Mario Langhi, Wilson Baleotti, Rodrigo Buzinaro Suzuki, Antonio Fabron, Marcelo Ortega Ruiz, Carlos S Chiattone, Jose Orlando Bordin
Journal: Blood (2014)
Abstract LB-276: Effect of lay health worker intervention on complinace of hepatitis B vaccinations in Asian Americans: Randomizd control trial
Authors: Hee-Soon Juon, Frederic Kim, Carol Strong, Eunmi Park
Journal: Cancer Research (2015)

Abstract Background/Context: Asian Americans are at high risk with contracting the Hepatitis B virus (HBV). There are preventive measures with vaccinations that could be administered. However, there are several barriers that preclude Asian Americans from receiving the proper care. Purpose: To implement lay health worker (LHW) telephone intervention using randomized control trial. Setting: Asian American community-based organizations in the Baltimore-Washington Metropolitan area from April 2013 to March 2014. Participants: 232 Asian American adults who were unprotected and 18 years of age or older. Intervention: Calling those in the intervention group to remind to receive a 3-shot series for HBV vaccinations at month 1, 2, and 5. Data collection/analysis: In a parent study, 600 Asian Americans participated in study by completing pretest, reading photo novel, and doing free Hepatitis B screening. A week later, participants received the results (i.e., protected, unprotected, and infected). In this study, those unprotected was assigned to either intervention or control group. The intervention group received the LHW intervention. Seven months after the pretest, those unprotected (n = 187) were followed by phone. The outcome measure was whether they had received a series of vaccines over 6 months with 3 groups (none, 1 or 2 vaccines, and completed). Multinomial logistic regressions were used. Results: We found that those in the intervention group were more likely to have 1 or more vaccines than the control group, compared to no vaccination group (OR = 3.04, 95% CI, 1.16, 8.00). Also, those in the intervention group were more likely to complete a series of vaccinations than the control group, compared to no vaccination group (OR = 7.29, 95% CI 3.39, 5.67). We also found that time is the most important barriers preventing them from seeking hepatitis B vaccinations. Conclusion: The LHW intervention was successful in increasing the chances to protect them from HBV infection in high risk group of Asian Americans. This study suggests that it is very critical to implement this culturally integrated LHW intervention program to reduce liver cancer health disparities among Asian Americans. Mulitivariate mulitinomial logistic regression model for having hepatitis B vaccinations (n = 187)None vs. 1or 2 vaccinesNone vs completedOR (95% CI)OR (95% CI)Control1.001.00Intervention3.04 (1.16, 8.00)7.29 (3.39, 5.67) Citation Format: Hee-Soon Juon, Frederic Kim, Carol Strong, Eunmi Park. Effect of lay health worker intervention on complinace of hepatitis B vaccinations in Asian Americans: Randomizd control trial. [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 LB-276. doi:10.1158/1538-7445.AM2015-LB-276
Endocrine therapy is not effective in BRCA2 mutated breast cancers even when they express hormonal receptors
Authors: M. Pistelli, Z. Ballatore, R. Bracci, F. Bianchi, E. Maccaroni, L. Belvederesi, F. Bini, M. De Lisa, A. Della Mora, A. Pagliacci, N. Battelli, A. Santinelli, T. Biscotti, S. Cascinu
Journal: Annals of Oncology (2015)
552. Transduction of Salivary Gland Acinar Cells in Rodents with Adeno Associated Viral Vectors Results in Persistent Exocrine and Endocrine Release of Recombinant Proteins
Authors: Giovanni Di Pasquale, Paola Perez Rivero, M. Tora, William D. Swaim, Tayyab Sheikh, Leyla Teos, Sandra Afione, Changyu Zheng, Ilias Alevizos, Roberto Weigert, John A. Chiorini
Journal: Molecular Therapy (2015)

Salivary glands are secretory epithelial organs in the mouth that are important in oral health. Disorders affecting salivary glands such as Sjögren's syndrome and damage following radiation therapy for head and neck cancer result in significant lifestyle changes and oral discomfort in patients. Gene transfer studies to the salivary glands for therapeutic or physiology studies have been hampered by a lack of vectors for efficient long-term transduction of acinar cells within the gland. By using a combination of approaches we have identified AAV isolates able to efficiently transduce acinar cells. Membrane-Tomato floxed membrane-GFP transgenic mice in combination with AAV encoded CMV-CRE recombinase expression cassette were used to rapidly identify serotypes able to transduced acinar cells. Biodistribution beyond the salivary gland was measured using vectors encoding firefly luciferase and xenogen imaging. In order to study the secretory properties of transduced acinar cells we cannulated mouse parotid glands with AAV vectors encoding Gaussia Luciferase or recombinant parathyroid hormone containing a nerve growth factor signal peptide. We could observe that both proteins can be detected in blood and saliva for at least 1 month post cannulation. Moreover the ratio blood/saliva secretion could be altered by treatment with pilocarpine or isoproterenol offering a unique mechanism for regulating the release of recombinant proteins in the salivary gland.
PO49INHIBITING HOX PROTEIN FUNCTION IN GLIOMA STEM CELLS AS A NOVEL THERAPEUTIC APPROACH IN GLIOBLASTOMA
Authors: Tim Brend, Henry King, Helen Payne, Will Rogers, Hardev Pandha, Richard Morgan, Susan Short
Journal: Neuro-Oncology (2015)

INTRODUCTION: HOX genes are essential for embryonic development but are dysregulated in numerous cancers, including glioblastoma. High levels of HOX expression are characteristic of a subset of glioma stem cells (GSC) and have been associated with self-renewal capability and treatment resistance. We aimed to determine whether HOX proteins are a potential therapeutic target in glioblastoma. METHOD: HOX expression profiles were determined using quantitative RT-PCR. Patient-derived GSC, glioma cell lines and primary astrocytes were treated with HXR9, a peptide that disrupts the interaction between HOX proteins and their binding partner PBX. Cell viability was determined using the MTS assay. Combination peptide and radiation treatments were assessed by clonogenic assay. Sub-cutaneous xenografts of U87-MG cells were established in Balb/C Nude mice and tumours were treated with intratumoural injection of peptide and/or CT-guided fractionated radiotherapy. RESULTS: Patient-derived GSC showed variable HOX profiles, similar to previously reported HOX-high and -low signatures. HXR9 was potently cytotoxic in a number of GSC cultures, with IC50 values of 3-9 µM. In contrast, normal astrocytes were much more resistant (IC50 = 70 µM), as were the cell lines T98G and U87MG (70 and 35 µM, respectively). An additive cytotoxic effect was observed for combined HXR9 and radiation treatment in vitro, and HXR9 treatment resulted in delayed tumour growth in vivo, both alone and in combination with radiotherapy. CONCLUSION: The HOX inhibitor HXR9 showed potent cytotoxicity in cultured GSC and reduced the rate of tumour growth in vivo. Targeting HOX proteins is a potential adjuvant treatment for glioblastoma alongside current chemoradiotherapy.
Immunosuppressive Effects of Multipotent Mesenchymal Stromal Cells on Graft-Versus-Host Disease in Rats Following Allogeneic Bone Marrow Transplantation.
Authors: Oral Nevruz, Ferit Avcu, A. Ugur Ural, Aysel Pekel, Bahar Dirican, Mukerrem Safali, Elvin Akdag, Murat Beyzadeoglu, Tayfun Ide, Ali Sengul
Journal: Blood (2007)
Patient Characteristics and Initial Treatment Patterns in the United States for the Most Common Subtypes of Peripheral T-Cell Lymphoma (PTCL)
Authors: Lauren Pinter-Brown, Francine M. Foss, Kenneth R. Carson, Steven M. Horwitz, Steven T. Rosen, Barbara Pro, Massimo Federico, Christian Gisselbrecht, Eric D. Hsi, Andrei R. Shustov, Ranjana Advani, Tatyana Feldman, Mary Jo Lechowicz, Sonali Smith, Anil Tulpule, John P. Greer, Brad S. Kahl, Joseph Leach, Neil Morganstein, Carla Casulo, Steven I. Park
Journal: Blood (2014)