tbuckley/cabot-search huggingface dataset:
Abstract LB-377: Promoter methylation of the DAPK1 CLL predisposition gene is associated with chronic lymphocytic leukaemia risk
Authors: Ida Candiloro, Thomas Mikeska, Graham Giles, Gianluca Severi, Alexander Dobrovic
Journal: Cancer Research (2012)

Abstract The pro-apoptotic gene DAPK1 has been identified as a hereditary cancer gene in some cases of chronic lymphocytic leukaemia (CLL). The causative mutation acts to increase the probability of methylation of the DAPK1 gene. Moreover, DAPK1 promoter methylation has been demonstrated to occur in nearly all cases of CLL, leading to down-regulation of the gene. We hypothesized that DAPK1 methylation thus underlies most cases of CLL and that predisposition to CLL might be associated with predisposition to methylate the DAPK1 gene. We thus accessed a large epidemiological cohort in which blood had been collected from participants who were then followed up indefinitely. This enabled us to compare methylation at the DAPK1 promoter in peripheral blood leukocyte DNA taken from individuals who developed CLL and control individuals who did not develop cancer. A quantitative MSP-based approach was used to analyse three regions within the 1.3kb promoter CpG island; (i) 5′ of exon 1 and at the 5′ end of the island. (ii) 3′ of exon 1 and in the centre of the island and (iii) 5′ of exon 2 and at the 3′ end of the island. No significant difference was found at the 5′ or the 3′ends of the island. However, when the central region (immediately after exon 1) was examined, the difference between the cases and controls was highly significant (p = 0.004). These results strongly support an important role for DAPK1 methylation in the early pathogenesis of CLL. Whilst methylation at the central part of the CpG island is not known to regulate any transcript, it may be an important first step in the CLL process as a seeding event. This hypothesis is supported by the fact that methylation at either end of the promoter was more likely if methylation was also present in the centre (p= 0.02 for controls and 0.006 for cases). 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 LB-377. doi:1538-7445.AM2012-LB-377
THU0404 Clinicopathological Analysis of 18 Cases of Specific Subcutaneous Sarcoidosis in South Korea
Authors: S. Moon, E.-J. Park, K.-S. Shin, J. Kim
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Sarcoidosis is a multisystemic granulomatous disorder of uncertain etiology, which is rare in Asia. In particular, subcutaneous sarcoidosis is a specific cutaneous lesion of sarcoidosis that is rarely reported. <h3>Objectives</h3> The aim of this study is to evaluate the clinicopathological features of 18 pateints with specific subcutaneous sarcoidosis and their relationship with systemic feature of the disease. <h3>Methods</h3> All patients performed skin biopsy and diagnosed with subcutaneous sarcoidosis from 2003 to 2013 were reviewed. Histological finding and clinical characteristics were analyzed. <h3>Results</h3> Eighteen patients with specific subcutaneous sarcoidosis were observed. Mean age at diagnosis was 51.4 years and female were dominant (17 patients, 94%). The initial lesions of the patients were 12 infiltrated nodulopapule, 3 maculopapular eruption, and 2 scar sarcoidosis. Subcutaneous lesions were most frequently located in the extremities. Four (22.2%) of 18 patients demonstrated only specific cutaneous involvement during follow-up period and the rest of the patients presented systemic involvement which included 14 hilar and mediastinal lymphadenopathy with or wihout lung parenchymal lesion, 3 arthritis, 2 uveitis, or 1 splenic involvement. Serum angiotensin-converting enzyme level in patients with systemic involvement tends to be higher than those without, although there was no statistical significance. In most of the patients, subcutaneous nodules appeared at the beginning of the disease and only 3 cases present skin nodules within 6 months after diagnosis. Twelve (66.5%) patients were treated with oral steroid and 4 (22.2%) patients treated with hydroxychloroquine or colchicine. The nodules remitted spontaneously in less than 1 year in 2 patients. Three patients present relapse course with lung involvement and were treated with oral steroid with azathioprine, which showed partial remission. <h3>Conclusions</h3> Specific subcutaneous sarcoidosis is a quite uniform clinicopathological entity usually appearing at the beginning of the disease. It may present with nonsevere systemic involvement and showed favorable clinical outcome. <h3>Disclosure of Interest</h3> : None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.5278
UTILITY OF IODINE-123-METAIODOBENZYLGUANIDINE IMAGING IN PREDICTING CLINICALLY RELEVANT VENTRICULAR ARRHYTHMIAS IN PATIENTS WITH SYSTOLIC HEART FAILURE: A SYSTEMATIC REVIEW
Authors: Janardhana R. Gorthi, Venkata Alla, Ajay Kaja, Abhilash Akinapelli, Vimal Kandasamy, Claire Hunter, Aryan Mooss
Journal: Journal of the American College of Cardiology (2014)
Abstract 1661: Knockdown of Nrf2 in cancer cells suppresses tumor growth: implication for the inhibitory role in HIF-1α and ErbB2 signaling
Authors: Mi-Kyoung Kwak, Eu-gene Hur, Tae-Hyoung Kim, Sarala Manandhar, Bo-Hyun Choi, In-geun Ryu
Journal: Cancer Research (2011)

Abstract Nuclear factor-erythroid 2 (Nrf2) is the transcription factor regulating multiple antioxidant proteins and phase 2 detoxifying enzymes, and plays a crucial role in the cytoprotection against oxidative stress-associated damages. However, a potential role of Nrf2 in cancer biology has been emerged recently. In our mouse xenografts study, a stable knockdown of Nrf2 in cancer cells from the colon (HCT116 and HT29) and ovary (SKOV-3) strongly suppressed tumor growth. As an underlying mechanism, it was observed that a vessel formation and vascular endothelial growth factor (VEGF) expression were suppressed in Nrf2-inhibited colon cancer tumors. Suppressive effect of Nrf2 knockdown on angiogenesis was further evidenced by the chicken embryo chorioallantoic membrane assay and endothelial tube formation assay. The subsequent mechanism studies revealed that Nrf2-inhibited HT29 cells failed to accumulate HIF-1α protein under 1% O2 hypoxia, resulting in the limitation of the expression of HIF-1α target genes for angiogenesis. Whereas, a tumor growth suppression shown in SKOV-2 cells was associated with repressed expression of ErbB2 and the consequent increase in p27. Further experimental demonstrations showed that the expression of ErbB2 is inversely related with Nrf2 in other types of cancer cell lines; therefore, the cell growth is attenuated in these Nrf2-inhibited cancer cells. Taken together, our current study suggests that a stable Nrf2 inhibition in cancer cells suppresses tumor growth through the alterations in HIF-1α and ErbB2 signaling. Hence, Nrf2 may be a promising target to control cancer cell growth and chemoresistance. 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 1661. doi:10.1158/1538-7445.AM2011-1661
Abstract 3305: The role of carbonic anhydrase IX in tumor hypoxia, metastasis and the cancer stem cell niche
Authors: Frances E. Lock, Paul C. McDonald, Yuanmei Lou, Claudiu T. Supuran, Shoukat Dedhar
Journal: Cancer Research (2012)

Abstract Carbonic anhydrase IX (CAIX) is a hypoxia and HIF-1 inducible protein that regulates intra- and extracellular pH under hypoxic conditions, and promotes tumor cell survival and invasion in hypoxic microenvironments. shRNA-mediated depletion of CAIX expression in mouse and human metastatic breast cancer cells, capable of inducing CAIX in hypoxia, resulted in regression of orthotopic mammary tumors and inhibition of spontaneous lung metastasis formation. CAIX depletion led to caspase-independent cell death and reversal of extracellular acidosis under hypoxic conditions in vitro. In addition, the CD44+/CD24-/low “cancer stem cell” compartment, which exhibited hallmarks of EMT (E-cadherin low/SMA high) was significantly enhanced in hypoxia, but was severely depleted in shRNA-CAIX knock-down cells as well as in cells treated with CAIX small molecule inhibitors. CAIX depletion or inhibition of its activity prevented mesenchymal conversion of the stem cells and also resulted in the suppression of expression of several EMT and “stemness” regulator genes. Treatment of mice harboring CAIX-positive 4T1 and MDA-MB-231/LM2 mammary tumors with novel CAIX-specific small molecule inhibitors that mimicked the effects of CAIX depletion in vitro resulted in significant inhibition of tumor growth and metastasis formation in both spontaneous and experimental models of metastasis, without any inhibitory effects on CAIX negative tumors, or any adverse toxic effects. This was associated with significant depletion of cells expressing “cancer stem cell” markers. Furthermore, interrogation of 3,630 human breast cancers revealed CAIX to be an independent poor prognostic biomarker for distant metastases and survival. Our findings demonstrate that CAIX is vital for the survival of “cancer stem cells” in hypoxic niches as well as for the growth and metastasis of hypoxic breast tumors. It is a specific, targetable biomarker for breast cancer metastasis. 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 3305. doi:1538-7445.AM2012-3305
P4-01-02: Endocrine Resistance: Mechanism, Tumorigenic Capacities, and New Therapeutic Strategies.
Authors: GD Morrison, X Fu, S Ithimakin, MF Rimawi, MS Wicha, CK Osborne, R Schiff
Journal: Cancer Research (2011)

Abstract Background Endocrine therapy is the most effective therapies for estrogen receptor positive (ER+) breast cancer, but resistance is still a major clinical problem. Tumor initiating cells (TICs) in drug resistant tumors are believed to be part of the contributing factors for tumor relapse. Here we focused on the TICs and how they are related to HER2 expression and its downstream factors in acquired endocrine resistance models. Materials and Methods: We have established a panel of endocrine resistant cell models through long-term treatment with tamoxifen (Tam, 10−7M, &amp;gt;6 months). Resistance to tamoxifen treatment in cells (TamR) was confirmed by growth curve assays (Celigo, Cyntellect Inc., San Diego, CA). In vitro mammosphere assays were applied to assess the mammosphere forming ability of parental and resistant cells. Aldefluor assays (StemCell Technology) were performed to measure the aldehyde dehydrogenase (ALDH-1) expressing cell population as a marker of TICs. Flow analysis was performed to evaluate HER2 expression in the ALDH subpopulations of both parental and TamR cells. Immunofluorescence staining was further used to detect the expression of ER, HER2, phosphorylated STAT3, and β-catenin in sorted ALDH+/− subpopulations. Results: We found that endocrine resistant cells have a higher mammosphere forming ability than their parental counterparts. In addition, we showed that the ALDH+ subpopulation was significantly upregulated in all TamR derivative lines. Further analysis of the ALDH populations indicated that HER2, as well as downstream survival factors such as pSTAT3s727 and β-Catenin, are upregulated in the ALDH+ populations as compared to the ALDH-population, especially in TamR derivatives. Discussion: Our data suggest that deregulated HER or other growth factor receptor signaling can potentially lead to the enrichment of TICs as a potential contributor to endocrine resistance. We will further investigate the role and molecular signaling of TICs in endocrine resistance of breast cancer, as well as whether and to what extent more potent anti-HER inhibitors can improve endocrine sensitivity and circumvent resistance. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P4-01-02.
Liver and Lung Metastases of High-Grade Astrocytoma Showing Abnormal Tc-99m MDP Localization
Authors: MUSTAFA YILMAZ, A. SEMIH DOĞAN, ERKAN DEREBEK, HATICE DURAK
Journal: Clinical Nuclear Medicine (1997)

A 44-year-old man had a subtotal resection of a grade III astrocytoma in the left parieto-occipital region. He underwent radiotherapy to the operation site for recurrence. On whole-body bone scintigraphy that was performed 10 months later, multiple foci of increased activity in the skeleton, as well as multiple areas of abnormal MDP localization in the upper abdomen and in the right lung hilum, were observed. Computed tomography confirmed the typical appearance of metastatic lesions in the liver and lung.
Abstract 2102: High resolution fluorescence imaging of cellular DNA and RNA enabled by the synthesis of complex oligonucleotide libraries
Authors: Robert A. Ach, Alice Yamada, Peter Tsang, Katja Pekrun, Alicia Scheffer-Wong, Laurakay Bruhn
Journal: Cancer Research (2012)

Abstract Fluorescence in situ Hybridization (FISH) is a powerful technique for studying the structure, organization, and localization of nucleic acids within individual cells. However, the use of FISH has often been dependent upon access to cloned template DNA for the generation of probes. Clones for specific regions may be unavailable, or the genomic region of interest may contain repetitive and other non-informative sequences which can be problematic for FISH analysis. We have leveraged our ability to chemically synthesize DNA in massively parallel reactions to produce libraries of oligonucleotides up to 200 bases in length that can be used to generate FISH probes. The sequences of the oligonucleotides in these libraries are selected in silico using empirically determined criteria so as to avoid repetitive elements or regions homologous to other non-targeted loci. Using oligonucleotide library-derived FISH probes on DNA, human genomic regions as small as 1.8 kb and as large as whole chromosomes can be visualized in both metaphase and interphase cells using the same simple assay protocol. Because of the inherent flexibility in our probe design methods, we readily visualized regions rich in repeats and/or GC content. Using oligonucleotide library-derived FISH probes on RNA, we have been able to detect the localization of a variety of both coding and non-coding RNAs in fixed cells, using both conventional fluorescence and structured illumination microscopy. Simultaneous hybridization of FISH probes labeled with different fluorophores enables visualization of multiple sequences at once. Using probes designed specifically to transcribed vs. non-transcribed regions, we have been able to simultaneously detect DNA and RNA from the same locus in the same FISH assay. Our oligo FISH methods are readily compatible with the co-detection of cellular proteins by immunocytochemistry. The ability to generate high performance FISH probes using chemically synthesized oligo libraries that can work flexibly with co-detection of other molecules yields a valuable tool for studies of how localization of specific nucleic acids impacts biological function. 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 2102. doi:1538-7445.AM2012-2102
Detection of Hereditary Angioneurotic Edema by Demonstration of a Reduction in the Second Component of Human Complement
Authors: K. Frank Austen, Albert L. Sheffer
Journal: New England Journal of Medicine (1965)

ACUTE circumscribed subepithelial edema of the skin was recognized as a distinct clinical entity by Milton1 and by Quincke,2 and shortly thereafter was termed angioneurotic edema by Strübing.3 In 1888 Osler4 called attention to a rare hereditary form of this syndrome, transmitted as a mendelian dominant5 6 7 with irregular penetrance.8 , 9 Some 503 cases in 61 families have been reported,7 , 10 11 12 13 but in only two thirds are there sufficient family data to permit a reasonably firm diagnosis of angioneurotic edema of the hereditary type.Hereditary angioneurotic edema is characterized by recurrent, acute, circumscribed and transient subepithelial edema of the skin, gastrointestinal mucosa . . .
Proposed FDA Rule: Will It Speed New Drugs to Patients?
Authors: H. McIntosh
Journal: JNCI Journal of the National Cancer Institute (1988)

Journal Article Proposed FDA Rule: Will It Speed New Drugs to Patients? Get access Hugh McIntosh Hugh McIntosh Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 80, Issue 19, 7 December 1988, Pages 1514–1515, https://doi.org/10.1093/jnci/80.19.1514 Published: 07 December 1988
S73 Infrared Spectroscopy For The Detection Of Extended Field Carcinogenesis: A New Paradigm For Lung Cancer Screening?
Authors: J. Brown, L. Foreman, K. Oliver, R. Thakrar, A. Marechal, P. Rich, S. Janes
Journal: Thorax (2014)

<h3>Background</h3> Computerised Tomography (CT) has been shown to be the only lung cancer screening modality to be effective in reducing lung cancer specific mortality.<sup>1</sup> A minimally invasive technique to stratify those at greatest risk within the population of adult smokers may help to target CT screening more effectively. <h3>Rationale</h3> Tobacco smoke exposure causes a field of injury to the airways (including nose and mouth) that if detected may inform an individual’s risk of lung cancer.<sup>2</sup> Infrared spectroscopy (IR) is a technique that can detect subtle biochemical alterations in macroscopically normal cells. <h3>Methods</h3> Buccal cells were exfoliated from 76 patients including 38 smokers without and 38 with lung cancer (matched for age, gender and pack years). The cells were fixed onto IR windows and spectra recorded using synchrotron radiation (Diamond facility, Oxford). Data was acquired using x36 objective and 15 × 15 µm aperture in transmission mode; 256 interferograms at 4 cm<sup>-1</sup> resolution were recorded for 50 cells per sample. All samples analysed were confirmed to be cytologically normal. Outlying data was removed using principal component analysis and a prediction model built using partial least squares discriminant analysis. <h3>Results</h3> Smokers with lung cancer could be differentiated from matched smokers without lung cancer with a diagnostic accuracy of 80%. The spectral region showing greatest difference between groups was in the 1200–900 cm<sup>-1</sup> region; comparison to reference spectra shows that this is likely to represent a metabolic change caused by an increased abundance of glycogen or its derivatives. <h3>Conclusions</h3> We have shown for the first time that IR spectroscopy of macroscopically normal upper respiratory tract cells may have a role to play in the early detection of lung cancer. Future work will validate these findings and aim to develop this non-invasive test for use as a pre-screen to select those at greatest risk who may be enrolled economically into surveillance programs. <h3>References</h3> The National Lung Screening Trial Research Team. Reduced lung-cancer mortality with low-dose computed tomographic screening. <i>N Engl Med</i> 2011;365(5):395–409 Sridhar <i>et al</i>. Smoking-induced gene expression changes in the bronchial airway are reflected in nasal and buccal epithelium. <i>BMC Genomics</i> 2008;9(1):259
Patient-Reported Symptoms from a Diverse Group of Subjects with Hypereosinophilic Syndrome
Authors: Nicholas C. Kovacs, Linda Nelsen, Suyong Yun Kirby, Katy Benjamin, Olga Moshkovich, Nicole Holland-Thomas, Amy D. Klion, Paneez Khoury, Jonathan Steinfeld
Journal: Journal of Allergy and Clinical Immunology (2016)
AB0303 Osteoarthritis is the Most Frequent Cause of Rheumathoid Arthritis Misdiagnosis in A Colombian Specialized Center
Authors: D. Gomez, V. Giraldo, G. Saavedra-Martinez, A. Palomino, L. Villarreal, J. Bello-Gualtero, P. Santos-Moreno
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> There is a lack of expertise in the rheumatoid arthritis (RA) diagnosis in primary level medical centers in Colombia. Frequently, patients with osteoarthritis (OA) are misdiagnosed as rheumatoid arthritis (RA) in primary care centers, leading to wrong treatment and consequent clinical and pharmacoeconomic impact. <h3>Objectives</h3> The objective of this study was to describe demographic and clinical characteristics of a cohort of patients derived to a specialized RA center with presumptive RA diagnosis and finally diagnosed as osteoarthritis. <h3>Methods</h3> A descriptive, cross sectional study. Patients were referred and assisted to a specialized RA center in a 24 month period with presumptive diagnosis of this disease. A complete medical record was fulfilled by a rheumatologist; it was measured rheumatoid factor and anti-citrullinated antibodies, and other laboratories depending on each case. Also were made x-rays of hands, and in some cases of persistent doubt about the diagnosis was requested comparative MRI of hands. Frequencies and Percentages were calculated for the demographic and clinical characteristics of the cohort of patients. <h3>Results</h3> From a total of 3665 Patients derived to specialized in RA center with presumptive RA diagnosis, after medical and laboratory evaluation 1451 (39.6%) had a wrong RA diagnosis; of them 1116 patients (76.9%) had finally osteoarthritis diagnosis. Of these patients 790 (70.7%) were women and 326 (29.2%) men, with an average age of 59.7 (±12 years). Majority of these patients were followed by general physicians or internists and treated with non-biologic and biologic disease modifying anti-rheumatic drugs (DMARDs) in the past, for an average time of 4.5 years. <h3>Conclusions</h3> In this cohort of patients the most frequent diagnosis of patients misdiagnosed with RA was osteoarthritis, being more than two thirds of them, predominantly women. This shows the need for the implementation of specialized clinics in RA and educational strategies for primary care physicians in order to avoid the impact of this wrong diagnosis. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.5344
SP0019 How to Use MRI in Inflammatory Arthritis in Clinical Practice
Authors: M. Østergaard
Journal: Annals of the Rheumatic Diseases (2014)

<h3></h3> This presentation reviews the utility of MRI in the diagnostic workout of suspected and undifferentiated axial and peripheral inflammatory arthritis. Furthermore it briefly describes how magnetic resonance imaging (MRI) can be used for monitoring rheumatoid arthritis (RA), ankylosing spondylitis (AS), spondyloarthritis (SpA), and psoriatic arthritis (PsA), and for predicting the disease course. The position of MRI in recent EULAR recommendations will be discussed. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.6332