tbuckley/cabot-search huggingface dataset:
Abstract 4247: Iron controlled treatment can be novel therapeutic agent and biomarker of Bevacizumab
Authors: Toshiaki Ohara, Kazuhiro Noma, Shinichiro Watanabe, Teppei Ohnishi, Seishi Nishitani, Yasuko Tomono, Yuuri Hashimoto, Hiroshi Tazawa, Toshiyoshi Fujiwara
Journal: Cancer Research (2011)

Abstract [Introduction] Lung cancer is one of the most aggressive malignancies with poor prognosis. Many kinds of new medicine for chemotherapy have been developed and introduced in clinical practice, whereas the mortality has not been satisfied. Furthermore, development of new medicine for chemotherapy costs a vast sum of money, which leads expensive treatment. Therefore, It's expected that development of new strategy extremely enhances the efficacy of ordinary therapeutic strategy. Iron metabolism and its relationship with cancer cell have been studied for a long time. Iron overload is known to induce some kinds of cancer, which suggests that prevention of iron overload could be a therapeutic strategy of cancer prevention. In fact, iron deficiency is also known to suppress the tumor growth in vivo study. However the efficacy is not superior to the ordinary chemotherapy, it's not a standard therapeutic strategy of cancer. In this study, we demonstrated that iron deficiency induced the suppression of the tumor growth and unwillingly up-regulation of angiogenesis in vitro and in vivo studies. Moreover using Bevacizumab together strongly suppressed the tumor growth in NSCLC. This result suggests that Iron controlled treatment can be novel therapeutic agent and biomarker of Bevacizumab. [Materials and Methods] A549, H1299 NSCLC cell lines were used. In vivo study, Normal diet and Iron deficient diet are prepared. Normal diet and Iron deficient diet were fed for 3 weeks before implantation of A549 cells in athymic male nude mice(n=8/group). In Bevacizumab administration study, as shown above, Bevaicuzmab(5 mg/kg) was administrated twice a week in each diet group. In vitro study, Iron chelator deferasirox was used in vitro study. Cell viability was determined by WST-1 assay. Cell cycle analysis was measured by flow cytometry. To determine angiogenesis via hypoxia, western blotting analysis and VEGF ELISA assay were done. [Results] Tumor growth was suppressed in iron deficient diet group (p=0.0037). Bevacizumab revealed to have an additive effect to inhibit the tumor growth. Deferasirox reduces A549 and H1299 cell proliferation in a concentration manner via cell cycle arrest. Deferasirox induces VEGF in A549 and H1299 supernatant via up-regulation of HIF1a. [Conclusion] Iron controlled treatment can be novel therapeutic agent and biomarker of Bevacizumab. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4247. doi:10.1158/1538-7445.AM2011-4247
Case 40-1996
Authors: Alexander C. White, Eugene J. Mark
Journal: New England Journal of Medicine (1996)

Presentation of CaseA 58-year-old man was admitted to the hospital because of respiratory distress and hypotension.Seven years before admission, a routine radiograph of the patient's chest had been reported to show a “black spot” in a lung. He declined follow-up examinations. Fifteen months before admission, he began to have a chronic cough productive of clear sputum, progressive exertional dyspnea, fatigue, and weight loss. Seven months before admission, he immigrated to the United States from a Caribbean island to be cared for by his daughters who resided in this country. Two weeks later, he came to this hospital.The . . .
PO34MICRORNA INTRATUMOUR HETEROGENEITY IN GLIOBLASTOMA
Authors: Josh Branter, Jennifer Ward, Ruman Rahman, Stuart Smith
Journal: Neuro-Oncology (2015)

INTRODUCTION: It is now clear that intratumour heterogeneity exists in many cancers, with clear evidence of differential gene expression temporo-spatially in glioblastoma multiforme (GBM). MicroRNA (miRNA) profiling studies have identified risk-stratifying signatures in GBM, but it has not been clarified whether microRNA profiles vary in a similar fashion to gene expression within individual GBM tumours. METHODS: miScript Human Brain Cancer miRNA PCR Array was used to assess 84 miRNA's expression levels between distinct regions within primary GBMs. Primary tumour specimens (n = 2) were sampled in 4 distinct regions including enhancing and necrotic core, invasive margin and medial rim. miRNA expression was analysed with quantitative RT-PCR. Gene targets for analysis were selected with miRtarget gene prediction software, and protein levels were validated through immunohistochemistry (IHC). RESULTS: A large degree of intratumour heterogeneity was apparent in the samples. Among the most differentially expressed miRNAs were miR-137, miR-182-5p, miR-183-5p and miR-218-5p. Conversely, miR-129-5p, miR-15b-5p and miR-185-5p were the most consistently expressed miRNAs across regions. Homology existed between individuals with 8 common miRNAs differentially expressed between both central and edge regions. Protein levels of CDK6 and c-KIT nuclear accumulation were significantly elevated at tumour edges relative to core samples as predicted by microRNA profiling. CONCLUSION: The miRNA intratumour heterogeneity in GBM could produce significant profiling variation depending on spatial location of the sample within the tumour. Therefore, assessment of GBM miRNA signatures requires selective sampling from multiple distinct tumour regions.
T5 Circulating endothelial progenitor cells in smokers and patients with COPD are dysfunctional due to increased DNA damage and senescence
Authors: K Paschalaki, RD Starke, Y Hu, N Mercado, A Margariti, VG Gorgoulis, AM Randi, PJ Barnes
Journal: Thorax (2013)

<h3>Introduction</h3> Cardiovascular disease (CVD) is a major cause of death in smokers, particularly in patients with chronic obstructive pulmonary disease (COPD). Circulating endothelial progenitor cells (EPC) are required for endothelial homeostasis, and their dysfunction contributes to CVD. DNA damage has been recognised as an important contributor to CVD. Our aim was to investigate whether EPC from smokers and COPD patients are dysfunctional, and the role of DNA damage pathways in mediating endothelial dysfunction in these patients. <h3>Methods</h3> To investigate EPC dysfunction in smokers, we isolated and expanded blood outgrowth endothelial cells (BOEC) from peripheral blood samples of healthy non-smokers, healthy smokers and COPD patients. Endothelial senescence was measured by senescence-associated β-galactosidase (SA-β-Gal) activity. Expression of sirtuin (SIRT)-1, p16, p21, γ-H2AX and 53BP1 were measured by Western blotting and/or immunofluorescence confocal microscopy. SIRT1 activity was measured using a SIRT1 fluorescent activity assay kit. To investigate angiogenesis <i>in vivo</i>, BOEC were labelled with Vybrant DiI Cell-Labelling Solution, mixed with Matrigel and injected subcutaneously into the back of NOD. CB17-Prkdcscid/NcrCrl mice. Seven days later, the mice were sacrificed and the plugs were cryosectioned. <h3>Results</h3> BOEC from smokers and COPD patients showed increased DNA double-strand breaks (measured by γ-H2AX, 53BP1) and senescence (senescence associated-β-galactosidase activity, p16 and p21 levels) compared to non-smokers. Senescence negatively correlated with sirtuin-1 (SIRT1) expression and activity, a protein deacetylase that inhibits DNA damage and cellular senescence. Inhibition of DNA damage response by silencing of ataxia telangiectasia-mutated (ATM) kinase resulted in up-regulation of SIRT1 expression and decreased senescence. Interestingly, treatment of BOEC from COPD patients with the SIRT1 activator resveratrol or a selective ATM inhibitor rescued the senescent phenotype. Using the <i>in vivo</i> Matrigel plug assay, BOEC from COPD patients displayed reduced angiogenesis (capillary-like structures) and increased DNA damage, senescence and apoptosis (measured by 53BP1, p16, TUNEL and cleaved-caspase 3 staining) compared to non-smokers. <h3>Conclusions</h3> BOEC from smokers and COPD patients show reduced angiogenesis <i>in vivo </i>and display increased DNA damage and senescence, associated with reduced SIRT1 expression. These defects may contribute to endothelial dysfunction and cardiovascular events in smokers and COPD patients and could potentially constitute therapeutic targets for intervention.
Abstract 1783: Activated c-MET; a prognostic factor and potential therapeutic target for malignant peripheral nerve sheath tumors (MPNST)
Authors: Keila E. Torres, Markus Ghadimi, Suizhao Wang, Jun Liu, Alexander Lazar, Raphael E. Pollock, Dina Lev
Journal: Cancer Research (2010)

Abstract There is a crucial need for sensitive prognosticators and novel therapeutic approaches for better management of MPNST. These tumors harbor a dismal prognosis due to their chemoresistant nature and enhanced metastatic propensity. A large body of evidence suggests a role for the tyrosine kinase receptor c-Met in cancer and its utility as a target for cancer therapy is currently being investigated. Here we aimed to evaluate the role of the c-Met signaling pathway in human MPNST. Expression level of c-Met, its ligand HGF and phosphorylated c-Met was determined immunohistochemically in a tissue microarray of human MPNSTs (n = 96) and benign neurofibromas (n = 31). All three markers were found to be over-expressed in MPNST as compared to their pre-malignant precursors (neurofibroma; p&amp;lt;0.05). Furthermore, univariable and multivariable analyses identified a statistically significant correlation between activated-c-Met expression and poor patient outcome (HR=2.32, p=0.012 and HR=1.48, p&amp;lt;0.001, respectively). Human MPNST cell lines expressed c-Met, HGF, and activated c-Met to varying levels. An activating c-Met mutation (Exon 2: N375S) was identified in one cell line (T265); all cells evaluated (n=3) harbored c-Met and HGF amplification based on aCGH. c-Met activation resulted in significantly increased MPNST cell motility and invasion. Furthermore, c-Met activation enhanced the pro-angiogenic effects of MPNST. c-Met blockade (via siRNA or a small molecule inhibitor) abrogated the HGF-induced downstream signaling and MPNST cell migration/invasion. Dual blockade of c-Met and VEGFR significantly abrogated MPNST local and metastatic growth in vivo. In conclusion, Human MPNST tumors and cell lines express the c-Met receptor which, upon activation, results in increased MPNST migration, invasion, and angiogenesis. Inhibition of c-Met-mediated signaling could impair MPNST metastatic capacity, and therefore merits further consideration as a potential MPNST therapeutic target. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. 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 1783.
Teaching and Evaluating Residents' Epinephrine Autoinjector Use with the Epipen® Proficiency Assessment Tool (E-PAT)
Authors: Artemio M. Jongco, Scott J. Bodner, Ana Barrera, Joshua L. Brenner, Brianne Navetta-Modrov, Myriam Kline, Saima I. Chaudhry, Gregory Grimaldi, Barry F. Kanzer, Michal Tamuz
Journal: Journal of Allergy and Clinical Immunology (2016)
Abstract P2-11-12: Proactive approach to risk reduction and early detection of breast cancer related lymphedema
Authors: MR Fu, A Guth, R Kleinman, F Cartwright, J Haber, D Axelrod
Journal: Cancer Research (2012)

Abstract Advances in surgery and post-operative treatment continue to reduce the incidence of late effects of cancer treatment such as lymphedema. Yet, many breast cancer survivors still face considerable post-operative challenges as a result of developing lymphedema. The purpose of this study was to preliminarily evaluate a nursing educational and behavioral program “The Optimal YOU” to enhance lymphedema risk reduction, focusing on preventing inflammation-infection, promoting lymph drainage, and maintaining optimal Body Mass Index (BMI) as well as preoperative and subsequent follow-up assessment of limb volume changes and symptoms. A quasi-experimental design with repeated-measures was used. The Study outcomes included lymph volume changes by infra-red perometer, lymphedema-related symptoms, and BMI by Bioimpedance at pre-operative baseline, post-operative, 6-month, and 12-month follow-up. A total of 147 patients were recruited and received the program, 141 patients completed the study (4% attrition rate). Majority (over 90%) of patients maintained preoperative limb volume and improved their symptom experience at 12-month follow-up. During the study period, only 7 patients (5%) had measurable lymphedema. At 12-month follow-up, among the 7 patients who developed measurable lymphedema, 2 patients' limb volume returned to pre-operative level without compression therapy only by maintaining exercises of The Optimal YOU to promote daily lymph flow. About 80% of patients maintained or improved their preoperative BMI. Implementation of this nursing educational and behavioral intervention is effective to enhance lymphedema risk reduction and early detection. Findings of the study provided evidence to support the emerging policy change in lymphedema care, shifting treatment-focus care to proactive risk reduction. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P2-11-12.
Rapid and Severe Adverse Reaction to Adenosine During a Pharmacological Stress Test for a Myocardial Perfusion Scan
Authors: Deborah Pencharz, Ann-Marie Quigley, Margaret Hall, Thomas Lucien Joseph Wagner
Journal: Clinical Nuclear Medicine (2013)

Pencharz, Deborah; Quigley, Ann-Marie; Hall, Margaret; Wagner, Thomas Lucien Joseph MD Author Information
Identification of Type I Diabetic Patients at Increased Risk for Hypoglycemia during Intensive Therapy
Authors: Neil H. White, Donald A. Skor, Philip E. Cryer, Lucy A. Levandoski, Dennis M. Bier, Julio V. Santiago
Journal: New England Journal of Medicine (1983)

During intravenous insulin infusions (40 mU per kilogram of body weight per hour for up to 100 minutes), 9 of 22 patients with insulin-requiring diabetes mellitus had neurologic signs or symptoms of hypoglycemia, plasma glucose concentrations that were below 35 mg per deciliter (1.9 mmol per liter) and continued to decline, or both. This inadequate glucose counterregulation resulted from the combined effect of deficient glucagon and epinephrine responses. In 8 of the 9 patients with inadequate counterregulation severe hypoglycemia developed during subsequent intensive therapy, whereas such episodes occurred in only 1 of 13 patients with adequate counterregulation. Thus, an intravenous insulin-infusion test can prospectively identify patients who are at increased risk for recurrent severe hypoglycemia during intensive therapy for diabetes.
Abstract 2209: Integrative analysis of DNA copy number and gene expression in metastatic tumor cells from oral squamous cell carcinoma for the identification of genes associated with survival
Authors: Chang Xu, Yan Liu, Pei Wang, Wenhong Fan, Tessa C. Rue, Melissa P. Upton, John R. Houck, Pawadee Lohavanichbutr, David R. Doody, Neal D. Futran, Lue P. Zhao, Stephen M. Schwartz, Chu Chen, Eduardo Méndez
Journal: Cancer Research (2010)

Abstract To examine the impact of copy number aberrations (CNA) on gene expression in oral squamous cell carcinoma (OSCC) metastasis, we used Affymetrix 250K Nsp single nucleotide polymorphism arrays and U133 Plus 2.0 expression arrays, respectively, to interrogate the DNA and RNA from metastatic OSCC cells isolated using laser capture microdissection from lymph nodes of 20 patients. Overall, CNA accounted for expression changes in about 30% of the transcripts studied. With a false discovery rate &amp;lt; 1%, 530 transcripts (461 genes) were identified as to have significantly correlated CNA and expression. When tested using an independent dataset with expression profiles for 148 primary OSCC and 45 normal oral mucosa, the genes were enriched with candidates associated with OSCC (vs. normal oral mucosa) (n=174 transcripts differentially expressed) and OSCC-specific survival (n=32 transcripts associated), as compared to a random gene set of the same size (p &amp;lt; 0.001). We then fit two Cox models using the first two principal components derived from these two gene sets (‘174-transcript PCA’ or ‘32-transcript PCA’), and two other models that combined stage with either the 174- or the 32-transcript PCA score. The Area Under the Curve (AUC) for a model combining stage with 174-gene PCA was significantly higher than that for a model with stage alone (AUC=0.80 vs. 0.72, p = 0.042). Further investigation is warranted to confirm these findings and to examine the biologic role of these copy number-associated transcripts in OSCC metastasis and their potential as therapeutic targets. 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 2209.
Developmental transformations in attachment in middle childhood
Authors: Kathryn A. Kerns
Journal: Behavioral and Brain Sciences (2009)

Abstract The target article proposes a model to explain the emergence of sex differences in attachment in middle childhood and their implications for reproductive strategies. While biological factors are prominent in the model, little is said about the social context of middle childhood and its contributions. There is also a need to clarify the fundamental nature of attachment in middle childhood.
Abstract 2190: <i>ADAMTS8</i> at 11q25 is a tumor suppressor antagonizing Ras-signaling and methylated in multiple carcinomas
Authors: Gigi C. Choi, Yajun Wang, Jisheng Li, Lili Li, Jianming Ying, Brigette B. Ma, Qian Tao, Anthony T. Chan
Journal: Cancer Research (2011)

Abstract As opposed to most matrix metalloproteinases which facilitate tumor progression, a growing list of ADAMTS secreted protease members was reported to display tumor suppressive properties with their expressions frequently altered in diverse types of tumors. Here, ADAMTS8 was shown to be located at an LOH locus at 11q25 by array CGH. We further showed that ADAMTS8 was frequently downregulated or silenced in multiple cancer cell lines while broadly expressed in normal tissues. Analysis on the methylation status of the ADAMTS8 promoter CpG island showed that methylation was cancer-specific and ADAMTS8 methylation was correlated with the silencing of ADAMTS8. In addition, expression of ADAMTS8 could be restored with pharmacological or genetic demethylation and hence indicating that CpG methylation directly contributes to the downregulation of ADAMTS8. Aberrant methylation was also frequently detected in primary NPC, gastric and colorectal tumors, but seldom in normal tissues. Ectopic expression of ADAMTS8 led to marked inhibition of cell growth in colony formation assays and cell migration in wound healing assay along with the reduction of phosphorylated ERK protein. The inhibitory effect on tumor cell growth and Ras-ERK pathway by ADAMTS8 indicates its role as a functional tumor suppressor. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2190. doi:10.1158/1538-7445.AM2011-2190
FRI0097 Factors Associated with Major Depressive Disorder in Rheumatoid Arthritis Patients
Authors: T.A. Lisitsyna, D. Veltishchev, A. Gerasimov, O. Seravina, O. Kovalevskaya, A. Zeltyn, V. Krasnov, E. Nasonov
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Psychiatric disorders occur in rheumatoid arthritis (RA) patients very often. It is considered that major depressive disorder (MDD) in RA is stress-related and associated with disease activity and chronic pain. <h3>Objectives</h3> to determine the factors associated with MDD in RA pts by linear regression analysis. <h3>Methods</h3> 125 RA pts were enrolled in this study. 86% RA pts were women with a mean age of 47.4±11.3 (M±m). The disease activity was assessed by DAS28 score. 52% of RA pts had a high activity of disease (DAS28&gt;5,1). 67% RA pts were taking prednisone in mean dose 5±2.7 mg/day (M±m). 80% RA pts were taking DMARDs: most of them - methotrexate (45%) and leflunomide (21%). All patients were taking NSADs. MDD was diagnosed by psychiatrist in accordance with the DSM-IV after structured interview. Psychiatric scales used: Hospital Anxiety and Depression Scale, Perceived Stress Scale (PSS-10) and projective psychological methods for affectivity (anxious, melancholic or apathetic) type detection. We studied also the history of stressful life events before and during RA and adverse childhood experiences (ACEs) that included childhood (up to 11 years age) physical, emotional or sexual abuse; witnessing domestic violence; growing up with household substance abuse, mental illness, parental death or divorce (parental deprivation) and/or an incarcerated household member. Fatigue was evaluated using Fatigue Severity Scale (FSS). The Brief Pain Inventory (BPI) was used for pain assessment. <h3>Results</h3> Stressful life events preceded the RA onset in 97 (77,6%) pts and the RA exacerbations in 76 (60,8%) pts. ACEs, the parental deprivation most often, were reported by 97 (77,6%) RA pts. MDD was diagnosed in 43 (34.4%) RA pts. All RA pts with MDD had stressful life events history and ACEs. The factors associated with MDD were found during Pearson correlations. Then linear regression analysis was done and obtaining prognostic model showed that MDD was associated with ACEs (β=0,096), stressful life events before RA onset (β=0,303), apathetic or melancholic affects (β=0,179), such inflammatory factors as blood platelets number (β=0,338), swollen joints count (β=0,143), RA exacerbations number (β=0,123), the most intensive pain (BPI-max) (β=0,075) and fatigue (FSS≥4) (β=0,215) (area under the ROC curve =0,912). <h3>Conclusions</h3> MDD in RA pts connected first of all with stressful life events and associated with more intensive inflammatory signs, pain and fatigue. The results have confirmed studies on the impact of early and subsequent life stress on inflammatory responses which is biological basis of RA and MDD. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.2151
RELATION BETWEEN SEVERITY OF RELATIVE MYOCARDIAL BLOOD FLOW REDUCTION AND GLUCOSE METABOLIC ACTIVITY IN PATIENTS WITH CHRONIC ISCHEMIC HEART DISEASE.
Authors: Richard C. Brunken, Markus Schwaiger, Jan Tillisch, Robert Marshall, Michael Phelps, Heinrich R. Schelbert
Journal: Clinical Nuclear Medicine (1986)

Brunken, Richard C.; Schwaiger, Markus; Tillisch, Jan; Marshall, Robert; Phelps, Michael; Schelbert, Heinrich R. Author Information
P696 A COMPLEX HBV QUASISPECIES IN RT AND HBsAg CHARACTERIZES PATIENTS WITH ACUTE HEPATITIS B: A REFINED UDPS ANALYSIS
Authors: M. Aragri, N. Coppola, C. Alteri, C. Minichini, A. Battisti, C. Sagnelli, M.C. Bellocchi, M.A. Pisaturo, R. Salpini, M. Starace, F. Continenza, D. Armenia, L. Carioti, M. Pollicita, E. Sagnelli, C.F. Perno, V. Svicher
Journal: Journal of Hepatology (2014)