tbuckley/cabot-search huggingface dataset:
Abstract 3656: Methodology design for identifications of protein targets of chemopreventive isothiocyanates using click chemistry.
Authors: Ying Fu, Lixin Mi, Monika Aggarwal, Daniel M. Appella, Fung-Lung Chung
Journal: Cancer Research (2013)

Abstract Isothiocyanates (ITCs) derived from cruciferous vegetables are inhibitors of carcinogenesis in animal models and can induce cell cycle arrest and apoptosis in a variety of cancer cell lines. It is known that ITCs can conjugate with glutathione (GSH) and induce cellular oxidative stress; ITCs can also bind to intracellular proteins (e.g. tubulin) which may constitute a mechanism underlying their cancer preventive effects. To fully understand the cellular responses to ITCs, it is crucial to develop an unbiased method that can rapidly identify their protein targets. In this study, the direct protein targets of phenethyl isothiocyanate (PEITC) were investigated by using click chemistry. An alkyne-tagged ITC was used as an analog of PEITC, a known cancer prevention agent. The tagged ITC (N-(2-(4-methoxyalkyne)phenethyl)isothiocyanate (NPPEITC) was designed and synthesized with a moiety for copper-catalyzed Huisgen 1,3 dipolar cycloaddition reaction (click chemistry), the tagged ITC, NPPEITC, was also found to show similar biological activities to PEITC; The click-chemistry reaction conditions of copper-catalyzed azide-alkyne cycloaddtion (CuAAC) for NPPEITC and N-(2-(4-methoxyalkyne)phenylethyl)acetamide (NPA, a negative control) with biotin azide were optimized and the reaction product was isolated and analyzed by mass spectrometry. A model click reaction between NPPEITC and tubulin was employed to validate this method. The western-blot showed that the tubulin protein is modified by biotin after NPPEITC treatment then followed by click reaction with biotin azide. In contrast, no biotin was found on NPA treated tubulin. Secondly, cancer cells exposed to the tagged ITC (NPPEITC or NPA) was lysed and exposed to click chemistry reagents to conjugate ITC-adducted proteins with biotin for subsequent affinity purification; the ITC conjugated proteins were identified and quantified using proteomic analysis by LC/MS/MS.(Supported by NCI grant CA100853) Citation Format: Ying Fu, Lixin Mi, Monika Aggarwal, Daniel M. Appella, Fung-Lung Chung. Methodology design for identifications of protein targets of chemopreventive isothiocyanates using click chemistry. [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 3656. doi:10.1158/1538-7445.AM2013-3656
Abstract 1280: Nano-scale phospho-proteomic analysis to define diagnostic signatures and biomarkers of therapeutic activity in cancer
Authors: Alice C. Fan, Prajna Banerjee, Liwen Xu, Christina Kong, Chiara Sabatti, Francois Wilhelm, Peter Greenberg, Dean W. Felsher
Journal: Cancer Research (2012)

Abstract The ability to quantify changes in protein activity in a clinical setting is important for the development of therapeutics that target cancer signaling pathways. We have developed the use of a highly sensitive microfluidic nano-immunoassay (NIA, Nanopro1000) to quantify unphosphorylated, single- and multi- phosphorylated isoforms of proteins in clinical specimens including blood, bone marrow, and fine needle aspirates (FNAs). Using as little as 2 nanoliters of cellular lysate, we can measure over 40 proteomic parameters, and assess changes in proteins that mediate signal transduction, cell cycle progression and apoptosis. Using NIA to resolve different phosphorylated isoforms of individual proteins and directly measure percent phosphorylation has led to new hypotheses and approaches to biomarker development. To develop novel diagnostic biomarkers, we have analyzed MAP Kinase phospho-protein profiles for over 200 specimens collected from patients with hematopoietic and solid tumors. We found that quantifying even subtle differences in protein signaling between tumor calls and adjacent non-tumor tissue can distinguish various malignancies. We will also present preclinical and clinical data using NIA to develop biomarkers of therapeutic activity biologic activity of tyrosine kinase inhibitors (TKIs) in myelodysplastic syndrome and leukemia. One unanticipated finding has been that TKIs might preferentially inhibit or activate specific phospho-isoforms of proteins. Our NIA studies also suggest that dynamic changes in protein signaling may better predict therapeutic outcome than profiles from a single, pre-treatment time point. One example is that the decrease in single phospho-ERK2 (p-ERK2) is associated with response to TKIs in chronic myelogenous leukemia. Notably, measurements of the phospho-isoform at a single time point were not sufficient to distinguish the two groups, which may reflect that individual tumors may have different initial “set-points” for the pathway. In contrast, comparison of proteomic signatures serially sampled from patients before and during treatment can provide valuable information regarding degree of target kinase inhibition and also compensatory signaling that can not be gleaned from analysis of a single time point. Our studies using nanoscale proteomic analysis to profile tumor signatures and characterize biologic response to therapies have led to new potential strategies for developing biomarkers, moving us closer to individualized cancer therapy. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1280. doi:1538-7445.AM2012-1280
Tl-201 Imaging in the Diagnostic Work-Up of Squamous Cell Carcinoma Metastasis of Unknown Primary Origin
Authors: HAKAN DEMIR, FATMA BERK, OKAN ERDINCLER, SERKAN ISGOREN, CUMALI AKTOLUN
Journal: Clinical Nuclear Medicine (2002)

DEMIR, HAKAN M.D.; BERK, FATMA M.D.; ERDINCLER, OKAN M.D.; ISGOREN, SERKAN M.D.; AKTOLUN, CUMALI M.D., M.Sc. Author Information
SAT0274 High frequency of microscopic gut inflammation in axial and peripheral spondyloarthritis: The giant cohort
Authors: L. Van Praet, F. van den Bosch, P. Carron, H. Mielants, D. Elewaut
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> It has been recognized for a long time that about 60% of all spondyloarthritis (SpA) patients show microscopic inflammatory gut lesions, a fraction of which evolves into Crohn’s disease (1). However, since the first publications of these findings (1984-1985), the field of SpA has experienced major developments, among them the possibility to decrease the gap between onset of symptoms and diagnosis, particularly by the introduction of MRI of the sacroiliac joints. As a consequence of the introduction of the new ASAS classification criteria (2), it is now possible to identify early in the disease course patients with non-radiographic axial SpA (nr-axSpA). Additionally, the prevalence of reactive arthritis caused by acute bacterial infections has remarkably decreased over time, suggesting that the prevalence of mucosal inflammation may have declined. <h3>Objectives</h3> Our study was designed to ascertain whether the prevalence of gut involvement in SpA has changed and to compare its frequency between patients with early nr-axSpA versus more established diseases, such as ankylosing spondylitis (AS). <h3>Methods</h3> The Gent Inflammatory Arthritis and spoNdylitis cohorT (GIANT) is a prospective observational cohort in which patients diagnosed with axial and peripheral SpA according to the ASAS criteria are prospectively followed; at present 110 SpA patients have been included. Ileocolonoscopy was performed in 58 patients (28 men and 30 women), never being treated with TNF blockers. None of the patients reported suggestive gastrointestinal complaints for, or had a previous diagnosis of inflammatory bowel disease. Mean age was 36.6 years. Median symptom duration at the time of the ileocolonoscopy was 5 years. Sixty-nine percent of the patients were HLA-B27 positive. <h3>Results</h3> A normal gut histology was found in 51.7% of all patients, 22.4% patients showed acute lesions and in 25.9% chronic lesions were found. Men and women were equally affected. A similar prevalence was noted in nr-axSpA, established AS and peripheral SpA. Chronic gut lesions occurred in 37.5% of patients with a short symtom duration (&lt;2 years) versus 17.6% in patients with longer symptom duration. <h3>Conclusions</h3> Microscopic gut inflammation frequently occurs both in early and established axial SpA as well as peripheral SpA, suggesting that gut inflammation is inherent to the SpA disease concept. The observed prevalence is comparable to the prevalence 2 decades ago. <h3>References</h3> Mielants H, Veys EM, Cuvelier C, et al. The evolution of spondylarthropathies in relation to gut histology. II. Histological aspects. J. Rheumatol. 1995;22(12):2273-8. Sieper J, Rudwaleit M, Baraliakos X, et al. The Assessment of SpondyloArthritis international Society (ASAS) handbook: a guide to assess spondyloarthritis. Ann Rheum Dis 2009;68(Suppl 2):ii1-ii44. <h3>Disclosure of Interest</h3> None Declared
Abstract 747: Tumor vaccine adjuvant effect of TLR7 agonist Imiquimod is limited by inducing immusuppressive cells
Authors: Yushe Dang, Wolfgang M. Wagner, Ekram Gad, Mary L. Disis
Journal: Cancer Research (2011)

Abstract Toll-like receptor (TLR) agonists are immune stimulators and have been studied as potential vaccine adjuvants with great interest. We evaluated the adjuvant effects of the TLR7 agonist imiquimod as compared to GM-CSF, which is widely used as a vaccine adjuvant in clinical trials. We found that both topical imiquimod and intradermal GM-CSF effectively induced the accumulation and activation of dentritic cells in draining lymph nodes and equally enhanced OVA specific CD4+ and CD8+ T cell responses in an OVA-tg mouse model. We further evaluated the efficacy of tumor prevention of imiquimod and GM-CSF in a neu-transgenic (neu-tg) mouse model of human breast cancer which over-expresses both neu and IGFBP2 tumor associated antigens. The neu-tg mice were immunized with a vaccine composed of three immunogenic IGFBP2 peptides prior to being inoculated with syngeneic MMC tumor cells. The tumor growth was significantly inhibited in the groups which received GM-CSF as an adjuvant, but not in imiquimod-treated groups. We questioned whether imiquimod induces immune suppression in response to tumor associated antigens and assessed the frequencies of myeloid-derived suppressive cells (MDSC) and T regulatory cells (Treg) in the splenocytes after three immunizations. We found that both CD11c+GR1+ MDSC and CD4+FOXP3+Treg cells were significantly increased in imiquimod-treated mice, but did not increase in GM-CSF-treated group. Serum levels of IL-10 were also significantly increased in imiquimod-treated, but not in GM-CSF-treated group. IFN-gamma secretion in response to IGFBP2 antigen, on the contrary, was remarkably enhanced in the GM-CSF-treated mice, but not in the imiquimod-treated mice as tested by an IFN-gamma ELISPOT assay. Thus, the TLR7 agonist imiquimod, as a vaccine adjuvant did not achieve a protective effect on breast cancer growth. The limited anti-tumor effect observed is associated with elevated levels of immunosuppressive MDSC and Treg cells. These results may have significant implications in the future development of imiquimod as a vaccine adjuvant. 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 747. doi:10.1158/1538-7445.AM2011-747
Abstract 4495: Clinical implications of family history of prostate cancer in an active surveillance cohort
Authors: Chee L. Goh, Edward Saunders, Daniel Leongamornlert, Malgorzata Tymrakiewicz, Karen Thomas, Elizabeth Selvadurai, Ruth Woode-Amissah, Tokhir Dadaev, Nadiya Mahmud, Elena Castro, David Olmos, Michelle Guy, Koveela Govindasami, Lynne O'Brien, Amanda Hall, Rosemary Wilkinson, Emma Sawyer, Ali Amin Al Olama, Douglas Easton, Zsofia Kote-Jarai, Christopher Parker, Rosalind Eeles
Journal: Cancer Research (2012)

Abstract Background Prostate cancer (PCa) is one of the most heritable cancers and a positive family history (FH) of PCa increases risk to 1st degree relatives by over 2 fold. The search for causative genetic variants has led to genome-wide association studies, which have so far identified over 45 susceptibility loci associated with PCa. However, the clinical utility of FH status or PCa risk SNP profiles to predict disease progression or aggression is yet undefined. We explore their potential prognostic role in patients undergoing Active Surveillance (AS). Methods Those enrolled in the Royal Marsden Hospital AS study were eligible. FH was obtained using questionnaires. For those with missing/incomplete data, hospital records were used. Patients with positive FH were further stratified according to the involvement of 1st and/or 2nd degree relatives. For risk score analyses, DNA was genotyped using the Sequenom MassARRAY iPLEX platform and Taqman assays. The cumulative risk scores for each patient were calculated by summing risk alleles for each loci using the weighted effect as estimated in previous studies. FH status and the SNP risk scores were analysed separately against defined adverse outcomes in AS, including adverse histology on repeat biopsy and time to treatment, to determine their prognostic value. Results 439 patients were eligible for FH analyses. 31% of those have since undergone treatment and 13% have histological upgrade on repeat biopsies. On univariate analysis, there was no significant relationship between FH of PCa in any degree of relation, and biopsy upgrade or time to treatment. For risk score analyses, 391 patients’ DNA were studied. There was also no relationship between the calculated genetic risk scores and biopsy upgrade or time to treatment (p=0.57 and p=0.83 respectively). When analysing differences between the higher and lower genetic risk groups (defined as the top 25% and lowest 25% of the genetic risk distribution), there was again no relationship (p=0.85 and p=0.91 respectively). Conclusion FH status or currently known PCa SNP profile risk scores have not been shown to be prognostic factors and should not be used to influence decisions in AS. This is the first study analysing the implications of PCa risk SNPs in AS. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4495. doi:1538-7445.AM2012-4495
IMPROVING THE CLINICAL UTILITY OF THE FRAMINGHAM RISK FUNCTION FOR INCIDENT CORONARY HEART DISEASE BY THE ADDITION OF WEIGHTED MULTI-MARKER GENETIC RISK SCORES IN MORE THAN 40,000 INDIVIDUALS OF CAUCASIAN ANCESTRY
Authors: Carlos Iribarren, Meng Lu, Eric Jorgenson, Manuel Martinez, Carla Lluis-Ganella, Isaac Subirana, Eduardo Salas, Roberto Elosua
Journal: Journal of the American College of Cardiology (2016)
I-123 Imaging After Recombinant Human Thyroid-Stimulating Hormone to Diagnose Metastatic Disease in an Intubated Patient with Papillary Thyroid Cancer
Authors: Stephanie A Fish, Abass Alavi, Susan J Mandel
Journal: Clinical Nuclear Medicine (2002)

FISH, STEPHANIE A. M.D.*; ALAVI, ABASS M.D.†; MANDEL, SUSAN J. M.D.* Author Information
Long-Term Tracheostomy in Extensive Bilateral Bronchiectasis
Authors: Richard H. Overholt, Maurice S. Segal
Journal: New England Journal of Medicine (1957)

A VICIOUS circle often exists in patients with extensive bilateral "universal" bronchiectasis. The greater the loss of lung substance, the more vital that airways be free. As the number of bronchiectatic segments is increased, the functionable segments are reduced. This means that when the ventilatory mechanism can least afford obstruction of airways, there are larger collecting reservoirs from which the bronchi are flooded. Therefore, one of the primary aims in management, when it is not feasible to perform excisional surgery, has been to promote adequate bronchial drainage.The life-saving potential of short-term tracheostomy to tide patients over acute situations has . . .
Thrombasthenia and Thrombocytopenic Purpura
Authors: Benjamin Alexander, Greta Landwehr
Journal: New England Journal of Medicine (1949)

RECENT advances in the knowledge of blood coagulation clarify understanding of the hemostatic defect underlying various hemorrhagic disorders. The pathogenesis of hemorrhagic disease is usually attributable to disturbed retractility of the small blood vessels, as in vascular and allergic purpura; thrombocytopenia; deficiency of antihemophilic "globulin" — hemophilia§; insufficiency of prothrombin or its accessory factors — for example, hypoprothrombinemia, parahemophilia,2 deficiency of prothrombin A3 and accelerator globulin deficiency4; fibrinopenia; and presence of circulating anticoagulants — heparin5 or heparin-like substances.6 There are, however, clinical conditions in which the nature of the hemostatic dysfunction is obscure, such as those designated as . . .
IMPACT OF DIABETES MELLITUS ON VESSEL GEOMETRY AND THE RESPONSE TO FINAL KISSING INFLATION FOLLOWING SINGLE STENTING FOR CORONARY BIFURCATION: ANALYSIS OF VOLUMETRIC INTRAVASCULAR ULTRASOUND AND OPTICAL COHERENCE TOMOGRAPY
Authors: Masahiro Yamawaki, Yoshinobu Murasato, Daisuke Terashita, Toshiro Shinke, Hiromasa Otake, Kenichi Fujii, Yoshihiro Takeda, Shin-Ichiro Yamada, Yoshihisa Kinoshita
Journal: Journal of the American College of Cardiology (2015)
Endoscopic repair of a massive postoperative pancreatic juice leak through the bile duct stump due to pancreatobiliary maljunction
Authors: Claudia Diaz-Tobar, Awad El-Ashry, John Christein, Klaus Mönkemüller
Journal: Endoscopy (2014)

A 55-year-old woman underwent suprapancreatic resection of a large choledochal cyst, Todani type IVA, associated with pancreatobiliary maljunction (PBMJ), Komi type IIb [1] ([Fig. 1 a, b] and [Fig. 2]). The pancreatic parenchyma was not incised or cauterized during surgery.
Abstract 3914: Wilms Tumor-1 (WT-1) and its target genes in gliomagenesis
Authors: Archana Chidambaram, Catherine Dumur, Timothy E. Vanmeter, Helen Fillmore, William C. Broaddus
Journal: Cancer Research (2010)

Abstract WT-1 - a zinc-finger transcription factor - plays an important role during development, and is associated with the development of tumors of varied origins. Our laboratory has previously demonstrated the expression and importance of WT-1 in the growth of glial neoplasms. In this study, we have sought to identify its downstream targets in the specific context of gliomas. Methods &amp; results: Using Real Time RT-PCR and Western Blotting, we demonstrate an inverse correlation between WT-1 and one of its established targets- IGF-1R. Also, using the gene expression profiling technique, we have identified some of its other target genes in U251-MG cells. Key genes that are down-regulated with WT-1 silencing include: PDGF-D, TYMS, INPP5A, EPAS-1 and CD97, while genes that are found to be up-regulated with WT-1 silencing include: TIMP-3 and LZTS-1. These results have been validated at the RNA and/ or protein level using Real Time RT-PCR and/ or Western Blot analysis. Further, we demonstrate the effects of manipulating WT-1 levels on some of these newly identified targets, selected for their importance in different aspects of tumor biology. Conclusion: WT-1 is clearly implicated in the development and progression of gliomas. By identifying the molecular allies that help this protein promote oncogenesis, we hope to gain important insights for the development of a multi-molecular targeting strategy against these aggressive tumors Abbreviations: IGF-1R: Insulin-like growth factor-1 Receptor; PDGF-D: Platelet-Derived Growth Factor-D; TYMS: Thymidylate Synthetase; INPP5A- Inositol Polyphosphate-5-Phosphatase; EPAS-1: endothelial PAS domain protein 1; TIMP-3: Tissue inhibitor metallopeptidase-3; LZTS-1: leucine zipper, putative tumor suppressor 1. 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 3914.
Abstract 2430: Aromatase expression inhibits anoikis and promotes bone metastasis of ERα positive breast cancer cells
Authors: Zhao Liu, Keya De Mukhopadhyay, Lan Yu, Lu-Zhe Sun
Journal: Cancer Research (2011)

Abstract Aromatase is the rate-limiting enzyme that catalyzes the final step in estrogen biosynthesis. In postmenopausal women the ovary ceases to make estrogen. Although it has been shown that estrogen is produced locally in breast cancer (BCa) tissue of postmenopausal women for the proliferation and survival of ERα (+) BCa cells, there is little information on the role and the regulation of aromatase in breast cancer cells for their survival when they intravasate into the circulation where estrogen level is very low. Human breast cancer CAMA-1 cell along with aromatase-transfected MCF-7 (MCF-7/Aro) and ZR-75-1 (ZR-75-1/Aro/CL10) cells were cultured in suspension to mimic circulating tumor cells. Interestingly, all the three ERα(+) BCa cell lines expressed more aromatase in suspension culture compare to the adhesion culture. Moreover both endogenous and transfected aromatase were upregulated in suspension culture. Additionally, a higher expression of ERα was also observed in suspension culture, which could increase the sensitivity of the breast caner cells to intracrine estrogen. We found that anoikis was shown to be inhibited by the supplementation of testosterone, which is converted to estradiol by aromatase. Conversely, addition of the aromatase inhibitor letrozole blocked the testosterone-induced anoikis inhibition. The increase of pro-apoptotic protein BAX and BAD were observed in suspension culture, while the treatment of estrogen inhibited the expression of BAX and BAD in both adhesion culture and suspension culture. More interestingly, mice with intracardiacally inoculated ZR-75-1/Aro cells presented distant bone metastasis in the mandible and tibiae/femora after 2-weeks of inoculation without estrogen supplement, while the control ZR-75-1 cells were incapable of forming metastasis without estrogen. Our findings provide an important foundation for future investigation on how hormone-dependent BCa cells survive in circulation during the process of metastasis. 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 2430. doi:10.1158/1538-7445.AM2011-2430
Case 38-2000
Authors: John Unterborn, Eugene J. Mark
Journal: New England Journal of Medicine (2000)

Presentation of CaseA 45-year-old woman was admitted to another hospital because of exertional dyspnea and bilateral pulmonary nodules.The patient was legally blind because of retinitis pigmentosa, which had been diagnosed at the age of three years, with loss of peripheral vision. She had been otherwise healthy until 16 months before admission, when she began to have exertional dyspnea, which gradually worsened. Four months before admission, a cough developed and became productive of sputum, which was blood-streaked after one episode of severe coughing. Radiographs of the chest (Figure 1) showed impaired inspiration and an ill-defined, patchy density, 1.5 cm . . .
CARDIAC SYMPATHETIC INNERVATION IN PATIENTS WITH IDIOPATHIC PULMONARY ARTERIAL HYPERTENSION: RELATION WITH DISEASE SEVERITY AND THE EFFECTS OF BETA-BLOCKING THERAPY
Authors: Mischa T. Rijnierse, Jasmijn S. van Campen, Karin de Boer, Hendrik Harms, Marc Huisman, Pieter Raijmakers, Frances S. de Man, Martijn Heymans, Adriaan Lammertsma, Paul Knaapen, Harm Bogaard, Anton Vonk-Noordegraaf, Cornelis P. Allaart
Journal: Journal of the American College of Cardiology (2016)