tbuckley/cabot-search huggingface dataset:
Abstract 3064: A novel method for mutation analyses using genomic DNA obtained from IHC-stained sections
Authors: Rupal M. Desai, Rajesh Patel, Lukas Amler, Howard Stern, Rajiv Raja
Journal: Cancer Research (2011)

Abstract Biopsies obtained from patients are often limited in size. The ability to perform multiple diagnostic assays is dependent on the quantity and quality of tissue samples available from patients. Over the last few years, our laboratory has focused our efforts on developing novel methodologies for increased efficiency in use of tissue samples. Here we describe a method for performing immunohistochemistry (IHC) and genotyping using the same tissue section. We isolated genomic DNA (gDNA) from IHC-stained and unstained formalin-fixed paraffin-embedded (FFPE) tissue sections obtained from the same paraffin block. Quality and quantitylity of gDNA obtained from either sections were compared. We demonstrate that quality of gDNA obtained is acceptable for down-stream analysis using PCR techniques. We also show comparable specificity and sensitivity in detecting mutations using either sources of gDNA. This method has proven highly valuable in performing mutation analysis in certain tissue types such as lung cancer where tissue can be extremely limited. 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 3064. doi:10.1158/1538-7445.AM2011-3064
Abstract A6: Dissecting mechanisms of RANKL dependency in osteosarcoma
Authors: Alexander G. Beristain, Sam Molyneux, Marco A. Di Grappa, Rama Khokha
Journal: Cancer Research (2009)

Abstract Osteosarcoma is the most common bone tumor in adolescents, severely impacts quality of life, and ∼40% of patients die of metastases to lungs and liver. In an effort to study this poorly understood cancer, we have generated a novel transgenic mouse model of osteosarcoma (designated MOTO) through osteocalcin promoter-driven SV40 T-antigen expression. The MOTO model is 100% penetrant and recapitulates all critical features of the human disease including skeletal tumor distribution, radiology, histology, genomic instability and metastasis. Using genomic screens, we have identified the cytokine RANKL (Receptor Activator of Nuclear Factor kappa B Ligand), and its receptor RANK, to be aberrantly expressed in MOTO tumors and cell lines. Genetic studies using RANKL deficient MOTO mice reveal osteosarcoma to be broadly dependent on its expression. To further dissect the role of RANKL signaling in osteosarcoma, we have performed gain- and loss-of-function studies to determine if RANKL affects classic oncogenic cell parameters. Specifically, loss of RANKL in MOTO tumor cell lines inhibits invasion and soft agar colony formation, indicating its ability to contribute to tumorigenesis in a cell autonomous manner. To support this hypothesis, we are testing the effects of de novo RANK expression on the tumorigenic properties of osteoblastic cells. Together, these studies are dissecting the individual contributions of RANKL and RANK in controlling primary bone tumorigenesis. Citation Information: Cancer Res 2009;69(23 Suppl):A6.
THU0418 Automated interpretation of ANCA patterns – a new approach in the serology of ANCA associated vasculitis
Authors: D. Roggenbuck, I. Knütter, R. Hiemann, T. Brumma, T. Büttner, K. Großmann, K. Conrad, D. Reinhold, E. Csernok
Journal: Annals of the Rheumatic Diseases (2013)

Background Indirect immunofluorescence (IIF), utilizing ethanol-fixed neutrophils as substrate, is still the method of choice for detecting antineutrophil cytoplasmic antibodies (ANCA) in vasculitis. The conventional immunofluorescence microscopy for detection of ANCA is subjective and interlaboratory tests showed occasionally large variances in ANCA determination. Objectives Aim of this study was to develop a novel ANCA module for the automated immunofluorescence reading system AKLIDES® for detection of ANCA and to assess its diagnostic value. Methods Samples were analyzed by IIF with ethanol- and formalin-fixed neutrophils (ethN and formN). Seventy ANCA positive samples with defined antigen specificities (myeloperoxidase, n=20 and proteinase 3, n=50) were used as a “training set” for the development of the new ANCA module of AKLIDES®. Sera from 291 patients (“test set”) with ANCA associated vasculitis and other systemic rheumatic diseases were tested for ANCA using the novel ANCA module and conventional fluorescence microscopy. Results For the analysis of IIF patterns of the nucleus and cytoplasm new algorithms of image processing were developed by using the training set. The module is divided into two profiles for the recognition of ANCA patterns of ethN and formN. Furthermore, a differentiation between positive and negative samples and a detailed separation into the different basic patterns C-ANCA (cytoplasmic pattern) and P-ANCA (perinuclear pattern) were implemented. The ANCA module was evaluated with the test set of 291 sera with ethN and formN slides regarding to the differentiation between positive and negative samples and compared with the manual interpretation of the slides. The Cohen’s kappa values for this comparison were 0.871 for ethN and 0.866 for formN. Furthermore, the analysis of the “test set” with regard to the differentiation of the C-ANCA and P-ANCA pattern showed a high agreement for ethN (kappa =0.739), formN (kappa =0.742), and for the combined result (kappa =0.901). The resulting sensitivities/specificities and negative/positive likelihood ratios for the comparison between manual and automatic reading (ethN, formN and combined result) showed medium to high agreement. Conclusions In summary, a novel ANCA fluorescence pattern recognition algorithm could be implemented successfully into AKLIDES®. The preliminary investigation of the automatic reading of ethanol- and formalin-fixed neutrophils demonstrated a high diagnostic performance for the detection of ANCA. Further studies are needed to evaluate this novel fully automated method for initial screening of suspected vasculitis patients. Disclosure of Interest None Declared
Abstract 5183: Correlation of cell adhesion molecules expression and prognosis in clinically localized prostate cancer
Authors: José Pontes Júnior, Leopoldo Alves Ribeiro-Filho, Sabrina Thalita Reis, Luiz Carlos Neves de Oliveira, Marcos Dall'Oglio, Kátia R M Leite, Miguel Srougi
Journal: Cancer Research (2010)

Abstract Introduction and objective: E-cadherin and others adhesion molecules are responsible for the maintenance of the epithelial phenotype. Some studies have reported correlation between alterations in cell adhesion molecules expression and carcinogenesis, but their role in the prostate cancer is not clear. Our aim is to study the expression profiles of E-cadherin and catenins in localized prostate cancer and evaluate their association with recurrence after surgical treatment Methods: For this case-control study, we selected 111 patients with localized tumor submitted to radical prostatectomy. 60 of these patients have not presented recurrence after a median follow-up of 123 months. Recurrence was defined as a PSA level above 0.4ng/ml. E-cadherin and α, β and µ-catenins expression was evaluated by immunohistochemistry in a Tissue Microarray containing two samples from each tumor. We employed a semiquantitative analysis and considered normal when the expression was strong and diffusely positive. We correlated expression with recurrence using the χ2 test and p&amp;lt;0.05 was considered significant. Results: We observed normal expression for E-cadherin and α, β and µ-catenins in 77%, 42, 18% and 8% of patients respectively (figure 1). Correlation the expression of cell adhesion molecules with cancer recurrence after radical prostatectomy in the univariate analysis we found that these expressions were not associated with tumor outcome after surgery with more than ten years follow up (table1). Conclusions: In the present study we have shown a profile of cell adhesion molecules expression in localized prostate cancer who underwent surgery. Furthermore, we found that the expressions were not correlated with recurrence, which do not qualify these proteins as potential markers of prognosis for this tumor. 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 5183.
OP0038 Vertebral fractures prevalence and abdominal aortic calcification in men
Authors: I. Ghozlani, A. Rezqi, A. Mounach, L. Achemlal, A. Bezza, A. El Maghraoui
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Cardiovascular disease is the most common cause of mortality among men. Vertebral fracture assessment (VFA) imaging with a bone densitometer can simultaneously detect prevalent VFs and AAC an important cardiovascular disease risk factor independent of clinical risk factors. <h3>Objectives</h3> to study the relation between the prevalence and severity of VFs using VFA in asymptomatic men and the prevalence and severity of AAC. <h3>Methods</h3> we enrolled 709 men with mean ± SD (range) age, weight and BMI of 62.4±8.6 (45 to 89) years, 75.9±12.9 (40 to 163) and 26.4±4.0 (16.6 to 43.8) kg/m<sup>2</sup>, respectively. Lateral VFA images and scans of the lumbar spine and proximal femur were obtained using a GE Healthcare Lunar Prodigy densitometer. VFs were defined using a combination of Genant semiquantitative (SQ) approach and morphometry. VFA images were scored for AAC using a previously validated 24 point scale. <h3>Results</h3> VFs were identified using VFA in 475 (40.3%): 166 (26.0%) had grade 1 and 68 (14.2%) had at least one grade 2 or 3 vertebral fracture. The prevalence of grade 2/3 vertebral fractures was 42 (38.9%) in men with osteoporosis and was higher (p&lt;0.0001) compared to 15 (5.9%) in men with normal BMD and to 39 (11.2%) with osteopenia. VFA images showed that 82% of the evaluable participants did not have any detectable AAC whereas the AAC score distribution ranged between 1 and 15. Conversely, the prevalence of significant atherosclerotic burden, defined as a radiographic 24-point AAC score of 5 or higher, was 2.8% and concerned essentially patients over 66 years. The group of men with moderate/severe vertebral fractures had a statistically significant higher AAC score and higher proportion of subjects with extended AAC, and lower weight, height, and lumbar spine and total hip BMD and T-scores than those without a VFA-identified vertebral fracture. A positive statistical correlation was noted between age and the SDI, and a statistical negative correlation between the AAC score and lumbar spine and total hip BMD. Multiple regression analysis showed that the presence of grade 2/3 VFs was associated to AAC and osteoporosis in any site. <h3>Conclusions</h3> VFA imaging has the potential to contribute to identification of sub-clinical cardiovascular disease in men. <h3>Disclosure of Interest</h3> None Declared
Abstract LB-418: A live-cell miRNA reporter library for identifying non-genetic drug resistance networks at single-cell resolution
Authors: Gregory Leya, John Albeck, Joan Brugge
Journal: Cancer Research (2012)

Abstract The effectiveness of targeted cancer therapies is limited by cellular resistance. Emerging research has demonstrated that a major source of drug resistance is non-genetic: pre-existing heterogeneity in protein expression levels, or induction of adaptive feedback loops, can protect cells from the effects of kinase inhibitors and other drugs. Traditional genomic or proteomic techniques may fail to identify key resistance pathways because they do not stem from changes in genetic sequences, are often transient in nature, and may operate in only a subset of cells within a population. To address this challenge, we have developed a library of over 80 live-cell reporters that, in combination with high-throughput automated microscopy, enable the identification of transiently active resistance pathways in drug-treated cells. These reporters are based on miRNA regulatory sequences since numerous miRNAs have been implicated in drug resistance and because miRNAs can act as surrogate indicators for the activation of signaling pathways in which they participate. We have developed and validated a novel ratiometric reporter design for optimal detection of miRNA expression changes at single-cell resolution and have constructed retroviral reporters for miRNAs involved in apoptosis, cell proliferation, cancer stem cells, metabolism, and stress response. Live imaging of mammary epithelial cells treated with inhibitors targeting EGFR, PI3-K, mTOR, and Bcl-2 identified a set of 20-30 miRNA reporters with significant expression level alterations in surviving cells that are consistent with miRNA expression changes characteristic of cancer cells. Bioinformatic analyses of these miRNAs revealed commonly regulated pathways and downstream targets, including Bcl-2 and Cyclin-D. Thus, the reporter library is capable of identifying, in living cells, pathways involved in the cellular response to targeted cancer therapies. By identifying components of the signaling networks controlling inhibitor resistance, we hope to discover new drug targets that can be used to sensitize tumor cells to existing targeted therapies. The reporter library can be easily expressed in most cell lines of interest and should have broad utility for identifying transiently regulated pathways. 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-418. doi:1538-7445.AM2012-LB-418
THU0232 Pregnancy outcome in idiopathic inflammatory myopathy patients in a multicenter study
Authors: M. Vincze, A. Váncsa, K. Dankό, L. Plestilova, J. Vencovsky, K. Gheorghe, I. Lundberg, P. Charles, H. Balsam, E. Wegier-Szewczyk
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Immunological changes during pregnancy are in the centre of scientific researches. We already know that immunological pathways may go wrong during pregnancy in autoimmune diseases with some general complications like fetal loss and low birth weight but we have less informations about the outcome of pregnancy in idiopathic inflammatory myopathies, polymyositis (PM) and dermatomyositis (DM). <h3>Objectives</h3> Our aim was to assess the clinical features, organ complications, functional course, therapeutic response in patients with PM/DM according to the pregnancy status. <h3>Methods</h3> Medical records were retrospectively revised using a standardised protocol. 23 PM/DM patients with pregnancy were identified in four countries: Hungary (n=9), Czech Republic (n=8); Sweden (n=5) and Poland (n=1). Immunological and serological characteristics were measured by ELISA, immunoblot and immuneprecipitation. Autoantibodies to Jo-1, PL-7, PL-12, EJ, OJ, SRP, PM-Scl, Ku, Mi-2, U1-, SSA, SSB were detected by LIA. We used the Fisher's exact test for statistical analysis. <h3>Results</h3> These 23 patients had 33 pregnancies after or at the time of disease onset. 10 of them suffered from PM and 13 had DM or JDM. The most frequent symptoms were ILD, mechanic's hand, Raynaud phenomenon and arthritis. 19 pregnancies ended without complications giving life to healthy babies. In 13 cases complications, like intra-uterine growth retardation, intra-uterine death, abortion, extra-uterine gravidity occurred. These complications were most frequently seen in patients with PM than DM (p=0,0729). The relative risk of complicated pregnancy in PM was 1,923 (CI 95% 1,041-3,553). This "almost significant" finding could be caused by PM and by anti-Jo1 and anti-phospholipid autoantibodies as well, because we found these antibodies frequently associated to PM in these cases. 13 pregnancies started during the active phase of myositis and the majority of these patients didn't reach remission after the delivery. The mean weight (2599g in active disease vs. 3342g in remission) and height (48 cm vs. 51 cm) of babies was lower in the active cases and the pregnancy ended earlier than in patients with remission. Most of the affected patients used only glucocorticoid treatment during pregnancy. <h3>Conclusions</h3> Complications during pregnancy were frequently reported in PM/DM although no myositis specific complications could be found. In patients with PM there was a tendency for a higher risk of fetal problems than in DM. <h3>Disclosure of Interest</h3> None Declared
Abstract 3712: p21-activated kinase-1 in the prevention of inflammation-driven colon cancer.
Authors: Vineeta Khare, Kyle Dammann, Manuela Jambrich, Andres Roig, Jerry Shay, Christoph Gasche
Journal: Cancer Research (2013)

Abstract Chronic gut inflammation in inflammatory bowel diseases (IBD) predisposes to the development of colorectal cancer, causing increased mortality. Use of mesalamine in the treatment and remittance of ulcerative colitis (UC) modulates the risk of neoplastic progression. We have previously reported (Khare V, et al. Biochem Pharm 2012) that p-21 activated kinase-1 (PAK1) mediates mesalamine activity by orchestrating MAPK signaling; Wnt-β catenin pathway and cell adhesion; all implicated in the colon carcinogenesis. Since mesalamine has primarily an anti-inflammatory function, we evaluated the role of PAK1, its target, in IBD and in colitis-associated cancer (CAC). PAK1 expression was scored by immunohistochemistry in human samples from IBD, CAC and normal mucosa. Compared to normal mucosa and Crohn's disease, a higher PAK1 expression was detected in UC which further increased in CAC. PAK1 expression was also elevated in the inflamed mucosa and carcinomas in IL-10−/− mouse model of colitis. The efficacy of mesalamine in reducing inflammation and tumor incidence in these mice has been previously reported (Brown JB et al, Gastroenetrology 2010). The consequence of PAK1 overexpression was further investigated in vitro. Normal diploid colon epithelial cells (HCEC-1CT) showed higher proliferation (46 ± 3.1% increase) upon overexpression of wildtype (wt) PAK1 while dominant negative (dn) PAK1 overexpression reduced proliferation (25% ± 2.5 decrease) compared to control. Apoptosis (Annexin V staining) was reduced in HCEC-1CT overexpressing wtPAK1 (1.2% ± 0.40) compared to dnPAK1 (11.6% ± 0.3) and control (16% ± 0.83). Mesalamine treatment (20mM) was effective in counteracting the effect of PAK1 overexpression by reducing cell proliferation and inducing apoptosis. Treatment of cells with specific inhibitors (PD98059/LY294002/Rapamycin) of signaling pathways (MEK/PI3K/mTOR) demonstrated that mesalamine regulated PAK1 expression by the MEK, PI3K and mTOR signaling pathways. Our data indicate that (1) PAK1 is upregulated in UC and in CAC, (2) PAK1 may be utilized as a predictive marker for the development of CAC, and (3) PAK1 is a viable target for chemoprevention in the setting of colitis. Mesalamine counteracts PAK1 expression and its effect on cell proliferation and apoptosis. In the longterm management of UC mesalamine may protect from CAC through inhibition of PAK1. Citation Format: Vineeta Khare, Kyle Dammann, Manuela Jambrich, Andres Roig, Jerry Shay, Christoph Gasche. p21-activated kinase-1 in the prevention of inflammation-driven colon cancer. [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 3712. doi:10.1158/1538-7445.AM2013-3712
Treatment of Traumatic Brain Injury with Moderate Hypothermia
Authors: Donald W. Marion, Louis E. Penrod, Sheryl F. Kelsey, Walter D. Obrist, Patrick M. Kochanek, Alan M. Palmer, Stephen R. Wisniewski, Steven T. DeKosky
Journal: New England Journal of Medicine (1997)

Traumatic brain injury initiates several metabolic processes that can exacerbate the injury. There is evidence that hypothermia may limit some of these deleterious metabolic responses.
An Improved Method for Prenatal Diagnosis of Genetic Diseases by Analysis of Amplified DNA Sequences
Authors: Scott C. Kogan, Marie Doherty, Jane Gitschier
Journal: New England Journal of Medicine (1987)

We report the development of a rapid nonradioactive technique for the genetic prediction of human disease and its diagnostic application to hemophilia A. This method is based on enzymatic amplification of short segments of human genes associated with inherited disorders. A novel feature of the procedure is the use of a heat-stable DNA polymerase, which allows the repeated rounds of DNA synthesis to proceed at 63 degrees C. The high sequence specificity of the amplification reaction at this elevated temperature permits restriction-site polymorphisms, contained in the amplified samples, to be analyzed by visual inspection of their digestion products on polyacrylamide gels. By means of this method, we have performed carrier detection and prenatal diagnosis of hemophilia in two families with use of the factor VIII intragenic polymorphisms identified by the restriction enzymes BclI and XbaI. Predictions can be made directly from chorionic villi, without previous DNA extraction, and fetal sex can be determined by amplification of sequences specific for the Y chromosome. Specific amplification of genomic sequences with heat-stable DNA polymerase is applicable to the diagnosis of a wide variety of inherited disorders. These include diseases diagnosed by restriction-site variation, such as Duchenne's muscular dystrophy and sickle cell anemia, those due to a collection of known mutations, such as beta-thalassemia, and those due to gene deletion, such as alpha-thalassemia.
Ocular Manifestation of Electrical Burn
Authors: Bobby S Korn, Don O Kikkawa
Journal: New England Journal of Medicine (2014)

A 42-year-old male electrician presented to the eye clinic with decreasing vision 4 weeks after an electrical burn of 14,000 V to the left shoulder. His vision in both eyes was limited to perception of hand motions, with an intraocular pressure of 14 mm Hg in each eye.
Noninvasive Diagnosis by Doppler Ultrasonography of Fetal Anemia Due to Maternal Red-Cell Alloimmunization
Authors: Giancarlo Mari, Russell L. Deter, Robert L. Carpenter, Feryal Rahman, Roland Zimmerman, Kenneth J. Moise, Karen F. Dorman, Avi Ludomirsky, Rogelio Gonzalez, Ricardo Gomez, Utku Oz, Laura Detti, Joshua A. Copel, Ray Bahado-Singh, Stanley Berry, Juan Martinez-Poyer, Sean C. Blackwell
Journal: New England Journal of Medicine (2000)

Invasive techniques such as amniocentesis and cordocentesis are used for diagnosis and treatment in fetuses at risk for anemia due to maternal red-cell alloimmunization. The purpose of our study was to determine the value of noninvasive measurements of the velocity of blood flow in the fetal middle cerebral artery for the diagnosis of fetal anemia.
Sarcoid: An Unusual Mimicker of Classic Pulmonary Embolus
Authors: FRANK A. MORELLO, SEHAM A. ALI, FERNANDO CESANI
Journal: Clinical Nuclear Medicine (1998)

A patient had both the clinical presentations and the ventilation-perfusion scan that simulated pulmonary embolism so closely that anticoagulant therapy was administered. Computed tomography of the chest and Ga-67 citrate scintigraphy identified hilar adenopathy due to sarcoidosis as the cause of a ventilation-perfusion mismatch.