tbuckley/cabot-search huggingface dataset:
P3-11-07: Mammary Gland Biopsy To Examine Surrogate Endpoint Biomarkers of Preventive Agent Efficacy.
Authors: B Heckman-Stoddard, RA Lubet, AM Bode, CJ Grubbs
Journal: Cancer Research (2011)

Abstract Phase II breast cancer prevention trials examine agent activity by sampling and imaging the breast through core needle biopsy, fine needle aspiration, or imaging (e.g., mammography). The biomarker endpoints in normal or at risk breast tissue employed with biopsies or fine needle aspirates (e.g., Ki67 or apoptosis) have often not been formally validated relative to a tumor endpoint. In this study, we have attempted to examine these endpoints in a preclinical model for which we have final tumor data. In the methylnitrosourea (MNU)-induced rat mammary cancer model, estrogen receptor positive cancers develop that are histologically similar to a large majority of human tumors. Here we present a protocol for correlating surrogate endpoint biomarkers and agent efficacy in the same animal. Biopsy samples are taken of the normal mammary gland after MNU treatment, and a week later the animals are started on the preventive agent. After 2 weeks, a second biopsy is taken and the animals are followed for tumor development. To test the protocol, we examined surrogate endpoints of tamoxifen efficacy at human equivalent dosages (5mg/d and 20mg/d). Both doses of tamoxifen prevented the development of tumors in the MNU-treated rats. The pre/post biopsy analysis revealed a statistically significant reduction in Ki-67 consistent with the clinical trial data. Additional biomarkers of apoptosis and the chromosome condensation pathway will be presented. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P3-11-07.
Abstract 4871: Photoreactive stapled peptides to capture cancer proteins and define their sites of interaction
Authors: Craig R. Braun, Julian Mintseris, Evripidis Gavathiotis, Gregory H. Bird, Steven P. Gygi, Loren D. Walensky
Journal: Cancer Research (2011)

Abstract Protein interactions mediate the pathologic cellular activities that contribute to the development, maintenance, and recurrence of cancer. Whether fleeting or stable, homeostatic or aberrant, protein partnerships and their sites of contact form the basis for discovery of biological pathways, disease mechanisms, and opportunities for therapeutic intervention. When the biological activity of cancer-causing proteins is assigned to discrete structural subdomains, their mode of action, menu of protein targets, and explicit sites of target engagement are frequently unknown. Ideally, the evolutionarily honed substructures could be used to capture and thereby catalogue their protein targets; however, out of context from the whole protein, bioactive subdomains often unfold, resulting in loss of biological shape, potency, and specificity. In an effort to reclaim the enormous capacity of structured peptides to selectively bind and capture their protein targets, we combined peptide alpha-helix stabilization, photoaffinity labeling, proteomic analysis, and structure calculation to generate a new strategy for both (1) expanding our grasp of the static and dynamic alpha-helical interactome of cancer proteins and (2) localizing and targeting alpha-helix/protein interaction sites. We piloted our approach using photoreactive stabilized alpha-helices of BCL-2 domains or pSAHBs and demonstrate that they serve as high fidelity research tools capable of efficiently, selectively, and irreversibly crosslinking both static and dynamic protein targets for proteomic and mechanistic analyses. In addition, the compounds were applied to rapidly and correctly locate protein interaction sites on the anti-apoptotic targets BCL-XL and BCL-w. A unique and compelling feature of this approach is the ability to conduct rigorous validation studies for the identified targets and their sites of interaction. Because stapled peptides can penetrate intact cells and access their intracellular targets, stapled peptide derivatives of the very reagents used for covalent capture can be applied to vet and potentially drug the cancer-causing interactions in vivo. 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 4871. doi:10.1158/1538-7445.AM2011-4871
Case 35-2004
Authors: Samuel L. Moschella, Jonathan Kay, Bonnie T. Mackool, Vincent Liu
Journal: New England Journal of Medicine (2004)

Thickening of the skin of the arms and legs, with flexion contractures of the knees, elbows, fingers, and toes, developed in a 68-year-old man with long-standing diabetes mellitus complicated by retinopathy, neuropathy, and renal failure. He was unable to walk and had nonhealing ulcers on both heels. Examination disclosed brown-pigmented, indurated plaques on the arms and legs. A diagnostic procedure was performed.
Role of endoscopic ultrasound-guided fine-needle aspiration in the diagnosis of pancreatic lesions
Authors: Guo Wen, Cheng Tian-ming, Zhu Wei, Zhou Dan, Zhi Fa-Chao, Jiang Bo
Journal: Endoscopy (2011)

Objective: Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) has become a widely accepted effective modality for obtaining tissue for primary diagnosis of the pancreatic lesions. The aim of this paper is to report our initial experience of this procedure for 35 patients with space-occupying lesion of the pancreas. Methods: We retrospectively reviewed the data on 35 EUS-FNA procedures performed in 35 patients for evaluation of the space-occupying lesion of the pancreas detected by CT scanning, ultrasonography or clinically suspected diagnosis. The sensitivity, accuracy and safety of EUS-FNA were evaluated. Final diagnosis was based on histological and cytological evidence or on follow-up. Results: All these 35 patients with pancreatic lesions were detected by EUS, however 20 patients and 29 patients were detected by transabdominal ultrasonography or CT scanning, respectively. A total of 35 EUS-FNAs were performed during the study period, and the diagnosis was made in 23 cases of pancreatic cancer, 9 cases of pancreatitis, 1 case of in traductal papillary mucinous neoplasm (IPMN), 1 case of pancreatic pseudocyst, and 1 case of serous cystadenoma. The sensitivity and accuracy of EUS-FNA for suspected pancreatic cancer were 73.91% and 82.86%, respectively. After EUS-FNA, 5 patients developed acutemild pancreatitis, and recovered soon following the treatment. Conclusion: Our experience confirms that EUS-FNA is a safe and valuable diagnostic method in patients with suspected space-occupying lesion of the pancreas. This technique should be considered the preferred test when a pathological diagnosis of a pancreatic lesion is required.
A8.14 CD39 and CD73 transgenic exosomes and recombinant fusion protein as novel therapeutics for the treatment of inflammatory disease
Authors: JD Finn, J van Ittersum, N Broekstra, PP Tak, MJ Vervoordeldonk
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background and objectives</h3> The conversion of extracellular ATP (eATP) to adenosine is an important mechanism of immune suppression through the coordinated activity of two enzymes, CD39 and CD73. CD39 is a membrane bound ATPase, and CD73 is a membrane bound ectonucleotidase that converts AMP to adenosine. We have previously presented evidence that the balance between pro-inflammatory eATP and anti-inflammatory adenosine is skewed in the synovial compartment of rheumatoid arthritis patients. Here we developed strategies for the use of CD39 and CD73 in inflammatory disease, including a soluble Recombinant Anti-Inflammatory fusioN (RAIN) CD39-CD73 fusion protein and transgenic exosomes containing CD39 and CD73. <h3>Materials and methods</h3> Whole blood inflammasome activation assay was performed by incubating whole blood with CD39-CD73 samples prior to 2 h LPS stimulation followed by a 1 h ATP stimulation. Pro-inflammatory cytokine/chemokine levels were measured by ELISA. Cell factories seeded with stably expressing 293 cells were used for large scale production of RAIN or CD39-CD73 exosomes. Conditioned serum-free media was collected every 3–5 days until a total of ˜10 L was collected. Conditioned media was concentrated (100 fold) by tangential-flow filtration (TFF) and RAIN was purified by anion-exchange chromatography, whereas exosomes were purified using Total Exosome Isolation reagent. Large scale batches of RAIN and exosomes were characterised by western blot and CD39-CD73 activities were measured by malachite green assay. <h3>Results</h3> Small scale batches of CD39-CD73 containing exosomes or RAIN were potent in reducing IL-1β secretion in a whole blood inflammasome activation assay (IL-1β EC50: RAIN ˜4000 pM, exosome ˜100 pM). Large scale production of RAIN was successful and yielded ˜2.5 mgs with ˜90% purity. The protein had a high specific activity (˜16000 U/μg CD39 activity, 24400 U/μg CD73 activity). Exosome purification yielded ˜25 mls of CD39-CD73 containing exosomes with ˜1316,4000 U/mL (36,5000 U/μg) CD39 activity and ˜253,9000 U/mL (13,5300 U/μg) of CD73 activity. These yields are sufficient for future <i>in vivo</i>studies. Interestingly, the exosomal enzymes had significantly higher specific activity (5–20 fold) when compared with RAIN. <h3>Conclusion</h3> These data demonstrate that exosome or fusion protein delivery of CD39 and CD73 is effective in reducing pro-inflammatory cytokine production <i>in vitro</i>, and that large scale production of CD39 and CD73 containing fusion protein or exosomes is feasible.
THE RELATIONSHIP BETWEEN SERUM VISFATIN LEVELS AND THE CORONARY SLOW FLOW PHENOMENON
Authors: Huseyin A. Cakmak, Serkan Aslan, Ahmet A. Yalcin, Ibrahim F. Akturk, Burce Yalcin, Fatih Uzun, Omer Celik, Derya Ozturk, Ali K. Kalkan, Mehmet Gul, Huseyin Uyarel
Journal: Journal of the American College of Cardiology (2015)
Therapeutic Effects of Pentaerythritol Tetranitrate in the Immediate Postmyocardial-Infarction Period
Authors: Hyman S. Mellen, Howard S. Goldberg, Herbert F. Friedman
Journal: New England Journal of Medicine (1967)

SINCE the introduction of anticoagulant therapy in cases of acute myocardial infarction in the 1950's no other drugs have become available to improve the immediate prognosis in this disease. The utilization of "coronary-care units" for the control of arrhythmias and vascular collapse, improvement in general nursing care and the earlier recognition of complications have been exceedingly helpful in influencing the course of this common disorder. In spite of these methods, hospital mortality in the immediate postinfarction period remains high, varying between 10 and 30 per cent even in the best hands.For many years nitroglycerin has been used routinely and . . .
Dual chitosan/albumin-coated alginate/dextran sulfate nanoparticles for enhanced oral delivery of insulin
Authors: Marlene Lopes, Neha Shrestha, Alexandra Correia, Mohammad-Ali Shahbazi, Bruno Sarmento, Jouni Hirvonen, Francisco Veiga, Raquel Seiça, António Ribeiro, Hélder A. Santos
Journal: Journal of Controlled Release (2016)
Biology of Airway Smooth Muscle
Authors: ALAN R. LEFF
Journal: American Journal of Respiratory and Critical Care Medicine (1998)

The 1998 Transatlantic Conference was dubbed by one of its participants as the symposium on a tissue that has no useful role. Perhaps so, but undaunted by the futility of discovering a function for airway smooth muscle, the participants dissected the challenging subject of the function of airway smooth muscle as a tissue and the potential mechanisms by which it plays a role in airway disease. Four major areas of focus emerged.
Uptake of In-111 Pentetreotide by Normally Functioning Nodular Goiters
Authors: S Garancini, S La Rosa, D De Palma, S Uccella, F Golonia
Journal: Clinical Nuclear Medicine (1997)

After the intravenous administration of a radiolabeled somatostatin analogue (octreotide), normal thyroid and neoplastic and nonneoplastic thyroid lesions can be visualized. The authors present the cases of two patients who underwent somatostatin receptor scintigraphy(SSRS) using In-111 pentetreotide: one for the study of suspected paraneoplastic ACTH hypersecretion, and the other for a restaging of breast carcinoma with neuroendocrine features. In both patients, SSRS revealed increased uptake in the thyroid, corresponding to "cold" nodules on Tc-99m pertechnetate imaging. Cytologic and histologic examinations showed the typical features of thyroid goiters without lymphocytic infiltration.
Abstract 1488: Role of human leukocyte antigen-G (HLA-G) in cancer progression and susceptibility
Authors: Ata Abbas, Syed R. Hussain, Hena Naqvi, Rabab Fatima, Sikandar Hasan, Farzana Mahdi
Journal: Cancer Research (2010)

Abstract Human Leukocyte antigen -G is an immunosuppressive protein with multiple functions. The 14bp insertion / deletion in exon-8 of HLA-G gene have been shown to play an important role in HLA-G mRNA stability as well as expression level; and can be correlated with its immunosuppressive function. The role of HLA-G in various cancers has already been demonstrated. Cancerous cells start expressing HLA-G which in turn provides a shield for various immune responses. In the present study we have tested the possibility of the role of 14bp insertion / deletion polymorphism of HLA-G in cancer progression and susceptibility. We have genotyped 59 cancer samples (26 benign and 33 malignant) and 79 matched controls for 14bp polymorphism of HLA-G. Data showed increase of +14bp/-14bp and −14bp/-14bp genotype with both benign and malignant cancer. We observed significantly higher frequency of +14bp/+14bp genotype in control (p=0.01). This is consistent with both benign and malignant tumors as well as cancer types showing possibility of protective effect of +14bp/+14bp genotype in various cancers. However, further studies will be required with large sample size to test this hypothesis. The +14bp/-14bp and −14bp/-14bp genotypes have already been shown to be associated with higher expression of HLA-G and its mRNA stability and might be providing favorable micro-environment for cancer progression. There is no published work till date showing the role of HLA-G 14bp polymorphism in various cancers. These preliminary data showed that HLA-G 14bp genotypes might be playing an important role in pathogenesis of various cancers. 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 1488.
TCT-457 Is There A Difference In The Clinical Presentation Of Patients With In-Stent Restenosis Of First- Versus Second-Generation Drug-Eluting Stents?
Authors: Marco A. Magalhaes, Sa'ar Minha, Salem Badr, Israel Barbash, Joshua P. Loh, lakshmana Pendyala, Hironori Kitabata, Al Fazir Omar, Rebecca Torguson, Fang Chen, Kenneth Kent, William O. Suddath, Lowell F. Satler, Augusto Pichard, Ron Waksman
Journal: Journal of the American College of Cardiology (2013)
Abstract 4994: Hypoxia-induced autophagy and TNF-alpha resistance in breast cancer cells leads to tumor evasion from NK-mediated immunosurveillance by downregulation of ICAM1.
Authors: Bassam Janji, Joanna Baginska, Sandrine Medves, Kris Van Moer, Salem Chouaib, Guy Berchem
Journal: Cancer Research (2013)

Abstract The major obstacle for defining efficient immunotherapeutic approaches for the treatment of solid tumor is the capability of tumor cells to evade host immune response under hypoxic microenvironment. We have investigated how breast cancer cells manage to evade effective immunosurveillance. Since the host's immune evasion of many breast cancer cells is correlated with the acquisition of resistance to TNF-α, we used TNF-sensitive (MCF-7) and TNF-resistant (1001) breast cancer cells. We showed that the acquisition of TNF resistance in 1001 cells is correlated with the induction of hypoxia inducible factor (HIF)-1α and a constitutive activation of autophagy. When cultured under hypoxia, TNF-sensitive tumor cells activate autophagy and resist to the cytotoxic effect of TNF-α. This data strongly argue for a role of hypoxia in the development of TNF-resistant tumor cell population. Furthermore, we showed that TNF-resistant cells evade natural killer (NK) cells-mediated lysis by a mechanism involving a decrease in the conjugate formation between TNF-resistant and NK cells. The decrease in the ability of NK cells to recognize TNF-resistant tumor cells is related to a dramatic down-regulation of Intercellular Cell Adhesion Molecule (ICAM-1) at the surface of tumor cells. The mechanism responsible for the decrease of ICAM-1 expression in TNF-resistant cells and its functional link with autophagy is currently under investigation. Together, this study discloses the major role of hypoxic microenvironment in the activation of the autophagic process in tumor cells which ultimately leads to tumor evasion from immunosurveillance. Citation Format: Bassam Janji, Joanna Baginska, Sandrine Medves, Kris Van Moer, Salem Chouaib, Guy Berchem. Hypoxia-induced autophagy and TNF-alpha resistance in breast cancer cells leads to tumor evasion from NK-mediated immunosurveillance by downregulation of ICAM1. [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 4994. doi:10.1158/1538-7445.AM2013-4994 Note: This abstract was not presented at the AACR Annual Meeting 2013 because the presenter was unable to attend.
SAT0087 Diagnostic Performance of Anti-Ccp Antibody at Annual Health CHECK Up
Authors: R. Rokutanda, Y. Haji, M. Kishimoto, C. Min, Y. Ohara, Y. Suyama, H. Shimizu, K. Yamaguchi, A. Takeda, Y. Matsui, S. Sasaki, M. Okada
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> There have been little data regarding epidemiology and usefulness of autoantibodies in general population. <h3>Objectives</h3> The purpose of this study is to describe epidemiological data about rheumatoid factor (RF) and anti-CCP antibody (ACPA) in Japanese general population and evaluate the usefulness of ACPA for detecting undiagnosed RA at annual health checkup. <h3>Methods</h3> During the period from November 2013 to January 2014, we checked RF and ACPA in all the female who visited St. Luke9s International Hospital Center for Preventive Medicine for annual health examinations. Patients who already had diagnosis of RA were excluded. Patients who had positive RF and/or ACPA are encouraged to visit our Rheumatology Clinic. First, we analyzed clinical characteristics of ACPA positive population. Then we divided seropositive referred patients into 3 groups; patients with positive RF and negative ACPA (Group A), patients with negative RF and positive ACPA (Group B), and patients who were positive for both of RF and ACPA (Group C). Rheumatology specialists examined all the referred patients and diagnosed them as either of RA, undifferentiated arthritis, or asymptomatic seropositive patient. <h3>Results</h3> During the study period, 3,610 consecutive Japanese female were checked RF and ACPA. The mean age was 49.9±24.5 yrs. The number of the seropositive patients for RF and ACPA are 397 (11.0%) and 53 (1.5%), respectively. Among them, 33 patients were positive for both of RF and ACPA. By multivariate analysis, ACPA positive population showed significant higher prevalence of positive RF (OR 11.7, 95% CI 6.35-21.69) and malignancy (OR 2.20, 95% CI 1.08-4.46) than those who with negative ACPA. Twenty-one of Group A, 3 of Group B, and 9 of Group C were referred to our Rheumatology Clinic. Among them, 4 (44.4%) of Group C are newly diagnosed as RA at first visit, while none of Group A and Group B were diagnosed as RA. In addition, 2 (9.5%) of Group A, 1 of Group B (33.3%), and 3 (33.3%) of Group C were diagnosed as undifferentiated arthritis. The specificities of RF and ACPA for detecting undiagnosed RA in referred patients were 10.3% and 72.4%, respectively. <h3>Conclusions</h3> In general population, non-RA ACPA positive female showed higher prevalence of positive RF and malignancy. In addition, ACPA showed high specificity for detecting undiagnosed RA in referred patients. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.4783
FRI0147 Data Driven Lesion-Based Criteria for Defining A Positive Sacroiliac Joint MRI in 2 Cohorts with Axial Spondyloarthritis: Table 1.
Authors: U. Weber, R.G. Lambert, S.J. Pedersen, S.M. Chan, V. Zubler, K. Rufibach, M. Ostergaard, Z. Zhao, W.P. Maksymowych
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> The ASAS definition of a positive sacroiliac joint (SIJ) MRI for axial spondyloarthritis (SpA) is based exclusively on bone marrow edema (BME). The contextual information of concomitant BME and/or erosion on T1SE and STIR sequences led to the MORPHO definition, which improved sensitivity without worsening specificity compared to the ASAS definition in a non-radiographic axial SpA (nr-axSpA) cohort of short symptom duration. <h3>Objectives</h3> To compare MORPHO and ASAS definitions for a positive SIJ MRI with global assessment by expert readers in patients with a broad spectrum of nr-axial SpA. To determine optimal lesion-based definitions for a positive SIJ MRI based on BME and/or erosion. <h3>Methods</h3> The sample comprised 2 independent cohorts A/B of 69/88 consecutive back pain patients ≤50 years, median symptom duration 1.3/10.0 years, newly referred to 2 university clinics for suspected SpA (A) or acute anterior uveitis (AAU) and back pain (B), and 20 healthy controls. Patients were classified according to rheumatologist expert opinion based on clinical examination, pelvic radiography and laboratory values as having nr-axSpA (n=51), AS (n=34), or MBP (n=72). SIJ MRI were assessed independently by 4 blinded readers according to standardized modules in which readers first recorded presence/absence of SpA by global evaluation of T1SE and STIR sequences, and subsequently reported whether BME or erosion were present for each SIJ quadrant on all MRI slices. We calculated sensitivity and specificity as mean values over 4 readers for global assessment, ASAS and MORPHO definitions. We derived candidate definitions based on the number of SIJ quadrants with BME and/or erosion to determine which might be optimal in both cohorts. <h3>Results</h3> For both cohorts, global assessment and “≥2 SIJ quadrants with erosion” showed the highest specificity. The MORPHO definition had increased sensitivity compared to the ASAS definition, with a slight drop in specificity. “BME in ≥3 SIJ quadrants” improved specificity over ASAS or MORPHO definitions although the combined criterion “≥3 BME and/or ≥2 erosions” showed both a higher sensitivity and specificity. <h3>Conclusions</h3> A stringent lesion-based definition of a positive SIJ MRI, based on both BME and erosion, performed best for classification of axial SpA. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.3413
Tc-99m DMSA and Tc-99m MAG3 Findings in Crossed Renal Ectopia
Authors: AMELIA JIMÉNEZ-HEFFERNAN, ANGEL C. REBOLLO, MANUEL GARCIA-MARTIN, CARMEN HERRERA, JAIME ACOSTA
Journal: Clinical Nuclear Medicine (1998)

A 2-year-old girl with failure to thrive underwent abdominal ultrasound which suggested a single kidney. Tc-99m DMSA imaging revealed a large, irregular reniform-shaped structure in the left abdomen and no activity on the right side. A dynamic study with Tc-99m MAG3 confirmed the presence of crossed renal ectopia with good function of both kidneys.
RNASEQ IDENTIFIES DIFFERENTIAL EXPRESSION OF PLATELET TRANSCRIPTS IN SUBJECTS WITH PERIPHERAL ARTERY DISEASE
Authors: Emilie Montenont, Tenzin Lhakhan, Jonathan D. Newman, Edna Bissoon, Matthew Cambria, Maya Rubin, Yajaira Suarez, Adriana Heguy, Aristotelis Tsirigos, Jeffrey S. Berger
Journal: Journal of the American College of Cardiology (2016)