tbuckley/cabot-search huggingface dataset:
AB1349 Safety and effectiveness of cosmetic minimaly invasive procedures among patients with systemic autoimmune disease
Authors: O. Reitblat, T.T. Lerman, T. Reitblat
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Noninvasive or minimally invasive cosmetic dermatologic procedures are considered safe with low parentage of reported adverse events. However, reliable prevalence data regarding adverse event of such cosmetic procedures among patients with systemic autoimmune diseases are insufficient. <h3>Objectives</h3> To assess the occurrence of adverse events and disease exacerbation associated with noninvasive or minimally invasive cosmetic dermatologic procedures, including those involving hyaluronic acid fillers, botulinum toxins and laser application among patients with systemic autoimmune diseases. <h3>Methods</h3> Consecutive cases of patients suffering from autoimmune diseases and attending the rheumatology clinic for regular follow-ups, were asked about receiving cosmetic procedures during the last two years. Medical history, including clinical and laboratory signs of disease exacerbation after the date of the procedure, was retrospectively obtained from medical files of the patients included in the study. Patients were also asked about subjective disease exacerbation and local adverse events after the procedure. <h3>Results</h3> During the three months of study period, 148 patients were inquired. Nineteen patients (89% females) underwent 23 cosmetic procedures in total. Thirty-nine percent had Rheumatoid arthritis (RA), 39% had Ankylosing spondylitis (AS) and 22% had other systemic connective tissue disease. Sixty seven percent were treated by Disease-modifying antirheumatic drugs (DMARDs), 28% by Biologic treatment and 5% did not receive any specific treatment. All patients were in remission during the cosmetic procedures. Forty three and a half percent of patients underwent hyaluronic acid injection, 21.7% botulinum toxin injection, 21.7% laser application, 8.7% mesotherapy and 4.3% silicon injection. None of the patients suffered from subjective disease exacerbation after the procedure. No changes in antibody titer and level of acute phase reactants (C-reactive protein and erythrocyte sedimentation rate) were noticed. Two patients (10.5%) experienced local oedema after filler injections. Both patients received Hydroxychloroquine treatment (one patient with RA and one with AS). <h3>Conclusions</h3> Our results suggest that noninvasive or minimally invasive cosmetic dermatologic procedures, including energy, neurotoxin, and filler procedures, may be safe among rheumatological patients, and do not cause autoimmune systemic disease exacerbation when performed in periods of remission. Hydroxychloroquine may predispose to a higher occurrence rate of local site injection adverse events. Further studied are desired to investigate this phenomena. <h3>Disclosure of Interest</h3> None declared
Abstract SY29-01: Role of nitrogen metabolism in obesity-associated pancreatic cancer
Authors: Nada Y. Kalaany
Journal: Cancer Research (2018)

Abstract Obesity is an established risk factor for pancreatic ductal adenocarcinoma (PDAC). Despite recent identification of metabolic alterations in this lethal malignancy, the metabolic dependencies of obesity-associated PDAC remain unknown. Here we show that obesity-driven PDAC exhibits accelerated growth and a striking transcriptional enrichment for pathways regulating nitrogen metabolism. We find that the mitochondrial form of arginase (ARG2), which hydrolyzes arginine into ornithine and urea, is induced upon obesity, and silencing or loss of ARG2 markedly suppresses PDAC. In vivo infusion of 15N-glutamine in obese mouse models of PDAC demonstrates enhanced nitrogen flux into the urea cycle, and infusion of 15N-arginine shows that Arg2 loss causes significant ammonia accumulation that results from the shunting of arginine catabolism into alternative nitrogen repositories. Furthermore, analysis of PDAC patient tumors indicates that ARG2 levels correlate with body mass index (BMI). The specific dependency of PDAC on ARG2 rather than the principal hepatic ureagenic enzyme ARG1 opens a therapeutic window for obesity-associated pancreatic cancer. Citation Format: Nada Y. Kalaany. Role of nitrogen metabolism in obesity-associated pancreatic cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr SY29-01.
BTEB2, a Krüppel-Like Transcription Factor, Regulates Expression of the SMemb/Nonmuscle Myosin Heavy Chain B (SMemb/NMHC-B) Gene
Authors: NoboruWatanabe, MasahikoKurabayashi, YukioShimomura, KeikoKawai-Kowase, Yo-ichiHoshino, IchiroManabe, MasafumiWatanabe, MasanoriAikawa, MakotoKuro-o, ToruSuzuki, YoshioYazaki, RyozoNagai
Journal: Circulation Research (1999)

We have recently characterized the promoter region of the rabbit embryonic smooth muscle myosin heavy chain (SMemb/NMHC-B) gene and identified the 15-bp sequence, designated SE1, located at −105 from the transcriptional start site as an important regulatory element for its transcriptional activity in a smooth muscle cell (SMC) line. In this study, we attempted to isolate cDNA clones encoding for the transcription factors that control the expression of the SMemb gene through binding to this cis-regulatory element. We screened a λgt11 cDNA library prepared from C2/2 cells, a rabbit-derived SMC line, by using a radiolabeled concatenated oligonucleotide containing SE1 as a probe. Sequence analysis revealed that one of the cDNA clones corresponds to the rabbit homologue of basic transcriptional element binding protein-2 (BTEB2), which has previously been identified as one of the Kruppel-like transcription factor. Gel mobility shift assays and antibody supershift analyses with nuclear extracts from C2/2 cells ...
Abstract 2441: Effects of hypoxia on Src family members' activity in prostate cancer cells
Authors: Yao Dai, Dietmar Siemann
Journal: Cancer Research (2018)

Abstract Metastasis is the major reason of disease progression and poor prognosis in prostate cancer. Src family kinases (SFKs), including c-Src, Lyn and Fyn, are non-receptor tyrosine kinases that have been shown to play an essential role in castration resistance and metastasis in prostate cancer. Hypoxia, a typical hallmark of solid malignancies, is able to promote metastasis-associated functions. However, whether SFK members are upregulated under hypoxia is unclear. The current project will detect the impact of hypoxia on cell functions and molecular features in prostate cancer cells. For hypoxic exposure, prostate cancer cells were exposed to low oxygen tensions (1% O2) for varied durations (0, 2, 6, 24 h). To test cell migration, “wound-healing” assay was used. Cell invasion was detected by seeding cells into Matrigel-coated transwell chamber and cells on the bottom membranes were counted after treatment. Clonogenic assay was performed to test cell survival. At the molecular level, SFKs' phosphorylation in cancer cells and patient tissues was detected by Western blotting, and gene knockdown was accomplished by siRNA transfection. To detect the effects of Src inhibitors, cells were treated with saracatinib for indicated time periods. Phosphorylation of all three typical SFKs, e.g., c-Src, Lyn and Fyn, were highly expressed in prostate cancer patient tissues. At the cellular level, while short term hypoxic exposure (2-6 h) induced greater effects than prolonged hypoxia (24 h) in PC-3ML, these cellular functions were increased with 24 h hypoxic exposure in C4-2B cells. Further, hypoxia enhanced SFK phosphorylation in the pattern that was consistent with cell functions in both cell lines. Knockdown SRC, but not LYN or FYN, abolished hypoxia-induced invasion and p-SFK expression. Lastly, SFK inhibitor saracatinib showed stronger inhibition on functional behaviors facilitated under hypoxia than normal conditions. Our data show that hypoxia is able to enhance metastatic phenotypes by activating SFKs in prostate cancer cells. Interestingly, c-Src may be the most important signaling molecule for hypoxia-mediated behaviors. More importantly, SFK inhibitors are able to impair hypoxia-induced cell functions, suggesting their therapeutic potential by suppressing tumor metastasis that is driven under hypoxia in prostate cancer. Citation Format: Yao Dai, Dietmar Siemann. Effects of hypoxia on Src family members' activity in prostate cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2441.
Mechanism of ST Elevation and Ventricular Arrhythmias in an Experimental Brugada Syndrome Model
Authors: MasaomiKimura, TakaoKobayashi, ShingenOwada, KeiichiAshikaga, TakumiHiguma, ShingoSasaki, AtsushiIwasa, ShigeruMotomura, KenOkumura
Journal: Circulation (2004)

Background— Although phase 2 reentry is said to be responsible for initiation of ventricular tachycardia (VT) in Brugada syndrome, information about the activation sequence during VT is limited. Methods and Results— We developed an experimental Brugada syndrome model using a canine isolated right ventricular preparation cross-circulated with arterial blood of a supporter dog and examined the VT mechanism. Two plaque electrodes (35×30 mm) containing 96 bipolar electrodes were attached to the endocardium and epicardium. Saddleback and coved types of ST elevation in transmural ECG were induced by pilsicainide, a pure sodium channel blocker, and pinacidil, a KATP channel opener. Eighteen polymorphic VT episodes were recorded in 9 of the 12 preparations associated with ST elevation. Fourteen episodes spontaneously developed in 5 preparations after an extrasystole during basic drive pacing. Analysis of local recovery times revealed increased dispersion especially in epicardium, and the extrasystole originated f...
Abstract 4684: NSD1 inactivation defines an immune cold, DNA hypomethylated subtype in squamous cell carcinoma
Authors: Kevin Brennan, Olivier Gevaert, John B. Sunwoo, June Ho Shin
Journal: Cancer Research (2018)

Abstract Normal 0 false false false EN-US JA X-NONE /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-parent:""; mso-padding-alt:0in 5.4pt 0in 5.4pt; mso-para-margin:0in; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:12.0pt; font-family:Cambria; mso-ascii-font-family:Cambria; mso-ascii-theme-font:minor-latin; mso-hansi-font-family:Cambria; mso-hansi-theme-font:minor-latin;} Chromatin modifying enzymes are frequently mutated in cancer, resulting in widespread epigenetic deregulation. Recent reports indicate that inactivating mutations in the histone methyltransferase NSD1 define an intrinsic subtype of head and neck squamous cell carcinoma (HNSC) that features pronounced DNA hypomethylation. We have identified a similar hypomethylated subtype of lung squamous cell carcinoma (LUSC) that is enriched for both inactivating mutations and deletions in NSD1. We identified cancer DNA methylation subtypes by first applying the MethylMix algorithm to whole genome DNA methylation and gene expression data from The Cancer Genome Atlas to identify DNA methylation deregulated genes, followed by consensus clustering to patients based on their profiles of these deregulated genes. The ‘NSD1 subtypes' of HNSC and LUSC are highly correlated at the DNA methylation and gene expression levels, featuring ectopic expression of developmental transcription factors and genes that are also hypomethylated in Sotos syndrome, a congenital disorder caused by germline NSD1 mutations. Further, the NSD1 subtype of HNSC displays an ‘immune cold' phenotype characterized by low infiltration of tumor-associated leukocytes, particularly pro-inflammatory M1 macrophages and CD8+ T cells, as well as low expression of genes encoding the immunotherapy target PD-1 immune checkpoint receptor and its ligands. Using an in vivo model, we demonstrate that NSD1 inactivation results in reduced T cell infiltration into the tumor microenvironment, implicating NSD1 as a tumor cell-intrinsic driver of an immune cold phenotype. NSD1 inactivation therefore drives widespread oncogene expression across cancer sites, and has implications for immunotherapy. &amp;lt;!–EndFragment–&amp;gt; Citation Format: Kevin Brennan, Olivier Gevaert, John B. Sunwoo, June Ho Shin. NSD1 inactivation defines an immune cold, DNA hypomethylated subtype in squamous cell carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4684.
Abstract 4598: A comprehensive assessment of the impact of preanalytical variables on cell free DNA and circulating tumor cells in blood
Authors: Anita Pottekat, Hatim T. Allawi, Genna T. Boragine, Michael W. Kaiser, Tamara Sander, Chateen Krueger, Janelle J. Bruinsma, Amber N. Murray
Journal: Cancer Research (2018)

Abstract Liquid biopsy continues to gain traction as a minimally invasive method to monitor biomarkers associated with malignancy and metastasis. A simple blood draw can reveal key biomarkers such as circulating tumor cells (CTCs) and cell-free DNA (cfDNA). However, these analytes are present in low quantities and are prone to rapid degradation and contamination, which presents challenges for the detection of rare CTCs and cfDNA targets. Higher molecular weight genomic DNA from poorly stabilized leukocytes can contaminate plasma, compromising liquid biopsy assay results by increasing the total amount of extracted DNA while diluting rare cfDNA targets. Preservation of CTCs and cfDNA over time is thus essential for the accuracy of downstream tests, and preanalytical variables that impact plasma volume, cfDNA yield and quality, and cell recovery in ex vivo blood must be understood. Here, we identified several preanalytical variables, including type of blood collection tube, storage time and conditions post-phlebotomy, and centrifugation conditions for plasma fractionation. We then carried out a series of studies to better understand the interplay between these preanalytical variables and plasma recovery, cell recovery, and cfDNA preservation in healthy donor blood, contrived samples, and patient samples. We found that choice of blood collection tube, in particular, has a significant impact on preservation of plasma volume, CTCs, cfDNA over time, particularly under real-world stress conditions including temperature excursions, sample shipping, and storage time post-draw. The work presented here demonstrates the importance of assessing preanalytical variables for the preservation of cancer biomarkers in whole blood without compromising sample integrity. This will ultimately help researchers make informed decisions on how best to stabilize their analytes of interest without introducing un-intended variables due to blood tube selection, shipping and storage conditions, and plasma isolation conditions. Citation Format: Anita Pottekat, Hatim T. Allawi, Genna T. Boragine, Michael W. Kaiser, Tamara Sander, Chateen Krueger, Janelle J. Bruinsma, Amber N. Murray. A comprehensive assessment of the impact of preanalytical variables on cell free DNA and circulating tumor cells in blood [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4598.
Evaluation of Left Ventricular Performance
Authors: Georgebenzing, Jamesstockert, Edwinnave, Samuelkaplan
Journal: Circulation (1974)

In the first part of the study, the influence of changes in preload and afterload on mean circumferential fiber shortening velocity, Vcf, was investigated in the absence of any extrinsic cause for change in the contractile state of the left ventricle (LV) of seven dogs. In five of seven dogs in which afterload was controlled and contractility was unchanged, there was a significant negative correlation between LV end-diastolic pressure and mean Vcf expressed in circumferences per second (r = –.88 to –.97). In one dog there was a positive correlation (r = +0.847) and in another dog there was no significant correlation. Correlation as a group was poor. In five of the above seven dogs in which afterload was decreased from a control level while preload was controlled and contractility was not extrinsically altered, mean Vcf increased in all instances. Because of the influence of afterload on Vcf increased in all instances. Because of the influence of afterload on Vcf and the inconsistent relation between Vcf a...
Abstract 106: Effect of Prehospital Portable Monitoring of Cerebral Regional Oxygen Saturation in Patients with Out-of-Hospital Cardiac Arrest
Authors: TomoyaHirose, TadahikoShiozaki, JunjiNomura, KazuyaKatsura, NaokiEhara, AkinoriWakai, MitsuoOhnishi, SumitoHayashida, DaikaiSadamitsu, TakeshiShimazu
Journal: Circulation (2014)

Introduction: In recent years, measurement of cerebral regional oxygen saturation (rSO2) has attracted attention during resuscitation. However, serial changes of cerebral rSO2 in pre-hospital settings are unclear. The objective of this study was to clarify serial changes in cerebral rSO2 of patients with out-of-hospital cardiac arrest in the pre-hospital setting. Hypothesis: A pre-hospital portable cerebral rSO2 monitoring system would be useful device in resuscitation. Methods: We developed a portable rSO2 monitor (HAND ai TOS®), which is small enough to carry in pre-hospital settings. The sensor is attached to the patient’s forehead by the Emergency Life-saving Technician (ELT), and it monitors rSO2 continuously. The normal range of rSO2 was determined from 15 healthy patients. Results: The normal range of rSO2 was 71.2±3.9%. From June 2013 through February 2014, serial changes of cerebral rSO2 in 4 patients were evaluated. In three patients in cardiopulmonary arrest when the ELT started cerebral rSO2 m...
Elevated IgE to tissue factor and thyroglobulin are abated by omalizumab in chronic spontaneous urticaria
Authors: Massimo Cugno, Riccardo Asero, Silvia Ferrucci, Maurizio Lorini, Vincenzo Carbonelli, Alberto Tedeschi, Angelo V. Marzano
Journal: Allergy (2018)

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Abstract B05: Cloning and vulnerability of intrinsically resistant subset of ovarian cancer stem cells
Authors: Guoqiang Chang, Jinxiu Li, Bailiang Wang, Yusuke Yamamoto, Rajasekaran Mahalingam, Marcin Duleba, Wei Rao, Jingzhong Xie, Shan Wang, Amir Jazaeri, Peter Davies, Suzy Torti, Giulio Draetta, Matthew Anderson, Molly Brewer, Christopher Crum, Frank McKeon, Wa Xian
Journal: Clinical Cancer Research (2018)

Abstract High-grade ovarian cancer is extremely sensitive to chemotherapy and yet usually lethal due to recurrent disease. To address the underlying mechanism of chemotherapy resistance in this disease, we employed novel technology developed to clone normal adult epithelial stem cells to generate libraries of patient-specific, clonogenic tumor cells. These clones possess hallmarks of “cancer stem cells” including long-term self-renewal and recapitulation of tumors of appropriate histology in immunodeficient mice. Significantly, these clonogenic tumor cells possess the overall pattern of genomic alterations of the whole tumor and yet display clone-specific patterns of variation reflecting intratumor heterogeneity that is stable despite months of continuous propagation. Our analyses at the clonal level have revealed a subset that display an intrinsic, pretherapy resistance to paclitaxel and hypervariable genomics in contrast to the bulk of clones sampled from the library. These intrinsically resistant clones share genomic and gene expression profiles with those surviving paclitaxel treatment of the whole library, suggesting a role for intrinsically resistant cells in recurrent disease. Remarkably, known drugs that interfere with signaling pathways enriched in both intrinsically resistant and paclitaxel survivor clones are synthetically lethal with standard-of-care chemotherapy. The targeting of intrinsically resistant clones from patient-specific libraries of cancer stem cells offers new strategies for preempting recurrent disease. Citation Format: Guoqiang Chang, Jinxiu Li, Bailiang Wang, Yusuke Yamamoto, Rajasekaran Mahalingam, Marcin Duleba, Wei Rao, Jingzhong Xie, Shan Wang, Amir Jazaeri, Peter Davies, Suzy Torti, Giulio Draetta, Matthew Anderson, Molly Brewer, Christopher Crum, Frank McKeon, Wa Xian. Cloning and vulnerability of intrinsically resistant subset of ovarian cancer stem cells. [abstract]. In: Proceedings of the AACR Conference: Addressing Critical Questions in Ovarian Cancer Research and Treatment; Oct 1-4, 2017; Pittsburgh, PA. Philadelphia (PA): AACR; Clin Cancer Res 2018;24(15_Suppl):Abstract nr B05.
Serum Dopamine-Beta-Hydroxylase Activity
Authors: Richardweinshilboum, Juliusaxelrod
Journal: Circulation Research (1971)

Dopamine-β-hydroxylase, the enzyme which converts dopamine to norepinephrine, is released into the perfusate upon stimulation of the isolated perfused adrenal gland and after stimulation of the nerves to the isolated perfused spleen. This study was undertaken to determine whether dopamine-β-hydroxylase activity could be detected circulating in blood. By using a sensitive new enzymatic assay, a dopamine-β-hydroxylase activity was found in the blood of both man and the rat. It is located in the serum and is not associated with the formed elements of blood. The serum activity is similar to that of purified bovine adrenal dopamine-β-hydroxylase in that it requires the presence of ascorbic acid, catalase, fumarate and oxygen for full activity. Furthermore, as is also the case with the adrenal enzyme, serum activity is increased in the presence of cupric ions. The Km values for substrate in human and rat sera are similar, and both are close to values determined in rat adrenal glands and stellate ganglia. The me...