tbuckley/cabot-search huggingface dataset:
AB0471 Granulomatosis with polyangiitis (gpa, wegener’s): complications and causes of death
Authors: O. Zimba
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> GPA is a necrotizing vasculitis with predominant involvement of the upper airways, pulmonary parenchyma and kidneys. In the absence of treatment prognosis for life is unfavorable. <h3>Objectives</h3> To determine the complications and causes of death in patients with GPA. <h3>Methods</h3> Specific causes of death of GPA were revealed based on clinical and pathomorphological data assessment of 11 fatal cases (8 men and 3 women, aged 16-74). <h3>Results</h3> Combined pulmonary and renal failure holds leading position among causes of death in patients with GPA (observed in six cases (54,5%). Destructive and productive panvasculitis, affecting small and medium sized vessels (capillaries, venules, arterioles, and arteries), were revealed in bronchial and pulmonary vessels. In the affected vessels thrombosis was found, causing hemorrhagic infarctions of lungs with frequent abscess formation. Histologically, the most common lesions of lungs were extravascular polymorphic necrotizing granular tissue in the form of pulmonary nodules with frequent cavitation. Disturbed circulation in lungs creates favorable conditions for the emergence of infectious complications - pneumonia, lung abscess, pleural empyema were observed in half of the cases. These changes significantly worsen thecourse of disease, increasing the risk of death. Analysis of pathological changes in kidneys showed that the most common lesions were diffuse necrotizing glomerulonephritis (63,7%), ischemic infarction (18,2%) and abscess (18,2%). Common cause of death from GPA was profuse hemorrhage from the eroded vessels of the upper respiratory tract, lungs and intestine. Our data showed that in four cases (36,4%) the disease was complicated by lethal bleeding. In two cases, the source of hemorrhage was duodenal ulcer. In other patients the cause of death was bleeding from eroded vessels of lung and trachea. Death from pulmonary hemorrhage occurred due to upper airway obstruction induced by asphyxia. The central nervous system pathology plays an important role in thanatogenesis of GPA. In 6 cases (54,5%) edema of brain tissue was observed, wherever in one case, the bulbar syndromewas dominating, characterized by dysarthriaanddysphagia due tothe weakness of soft palate, tongue and pharynx. The autopsy results showed edema of the brain, foci of demyelination and necrosis with cyst formation in the medulla oblongata. <h3>Conclusions</h3> The complications and causes of death in patients with GPA are: combined pulmonary and renal failure; profuse hemorrhage from the eroded vessels of the upper respiratory tract, lungs, intestine; infectious complications; central nervous system disorders. <h3>Disclosure of Interest</h3> None Declared
Reactivation of<i>Plasmodium malariae</i>Infection in a Trinidadian Man after Neurosurgery
Authors: Dave D. Chadee, Clive C. Tilluckdharry, Paramanand Maharaj, C. Sinanan
Journal: New England Journal of Medicine (2000)

To the Editor: Malaria often presents as an acute febrile illness with fever, headache, rigors, anemia, and splenomegaly. The only malaria parasite associated with cerebral complications, Plasmodiu...
Abstract LB-427: Differential effects of resveratrol-induced SIRT1 in prostate cancer: A novel therapeutic target
Authors: Guiming Li, Rita Ghosh, Addanki P. Kumar
Journal: Cancer Research (2010)

Abstract Silence information regulator (SIRT1) is a Nicotinamide adenine dinucleotide (NAD+)-dependent histone deacetylase that regulates various biological processes including cell survival, apoptosis, metabolism and aging. Given the role for calorie restriction (CR) in delaying the onset of aging and age-related disorders including cancers, efforts are under way to develop CR mimetics as therapeutic agents. Resveratrol, a CR mimetic activates SIRT1 and has been shown to extend life span. Further, resveratrol has been shown to prevent tumor development and cancer cell proliferation in a wide variety of models including prostate. However the precise role of SIRT1 in prostate cancer development and progression remains unexplored. Towards developing SIRT1 targeted preventive approaches, we conducted studies using human prostate cancer cell lines and a preclinical animal model that develops high grade prostatic intraepithelial neoplasia (HGPIN) in response to hormone stimulation. Our studies show that androgen independent prostate cancer cell lines (DU145 and PC-3) express higher levels of SIRT1 compared to non tumorigenic RWPE-1 consistent with the published results. Resveratrol-mediated inhibition of cell proliferation was associated with reduction in the levels of pAkt (Ser473 and Thr308), SIRT1and Cyclin D1 in PC-3 cells but not in DU145. Most interestingly we did not detect SIRT1 enzymatic activation following resveratrol treatment. Further pretreatment of prostate cancer cells with known pharmacological SIRT1 inhibitor (Nicotinamide) enhanced resveratrol mediated proliferation inhibition. Dietary intervention with increasing doses of resveratrol for 3 weeks showed no protective effect on the development of PIN lesions or chronic inflammation or atrophy in rats stimulated with hormones. Our studies show for the first time that (i) SIRT1 may not be a direct target of resveratrol; (ii) combination of resveratrol and SIRT1inhibitor may provide a new approach to prevent development and progression of prostate cancer. Supported by CA 137518 (APK). 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 LB-427.
Abstract 768: A role for c-Rel in ΔNp63α/v-RASHA-driven carcinogenesis?.
Authors: Kathryn E. King, Roshini M. Ponnamperuma, Sa Ra Park, Steven Jay, Linan Ha, Wendy C. Weinberg
Journal: Cancer Research (2013)

Abstract The p63 isoform ΔNp63α is expressed in basal keratinocytes and overexpressed in human squamous cell carcinomas, but the mechanisms whereby this p53 homologue contributes to cancer pathogenesis have yet to be elucidated fully. In mimicking the overexpression of ΔNp63α observed in squamous cell carcinomas using transient adenoviral transduction of primary murine kerationcytes, we showed that overexpression of ΔNp63α inhibits Ca2+-mediated growth arrest and biochemical differentiation. We previously reported that this block in growth arrest is mediated via the NF-κB subunit, c-Rel, which accumulates in a phosphorylated form in the nucleus of ΔNp63α-overexpressing cells and physically associates in a phosphorylation-dependent manner with ΔNp63α. Consistent with the observed effects on growth regulation, ΔNp63α:c-Rel complexes bind to a p63 binding site on the cdk inhibitor p21WAF1. To explore the biological impact of long-term ΔNp63α overexpression in primary murine keratinocytes, lentiviruses were developed. Consistent with our transient adenoviral vector studies, keratinocytes expressing lenti-ΔNp63α have enhanced proliferation rates over 15 days in culture relative to lenti-GFP controls. Using a nude mouse grafting model that allows distinction between normal, benign, and malignant growths, we previously reported that lenti-GFP keratinocytes expressing oncogenic v-rasHa form well differentiated papillomas at the graft site, while keratinocytes expressing lenti-ΔNp63α in combination with v-rasHa form undifferentiated carcinomas. To expand this model system to study c-Rel we first confirmed that lentivirus-driven ΔNp63α overexpression results in sustained nuclear accumulation of the NF-kB subunit c-Rel, consistent with our observations using the adenovirally transduced cultures. In the lenti-ΔNp63α expressing cultures, enhancement of c-Rel is observed beginning at day 5 post-infection and is maintained through the latest time point tested, 14 days. Lentiviral c-Rel shRNAs have been developed to assess the contribution of altered nuclear c-Rel expression to ΔNp63α-mediated growth regulation in vitro and in vivo and have been successfully used to knockdown c-Rel to the latest time point tested, 28 days. Taken together, these data support a role for ΔNp63α in facilitating keratinocyte transformation and provide a model system for elucidating the contribution of NFkB/c-rel to ΔNp63α /v-rasHa-driven carcinogenesis. Citation Format: Kathryn E. King, Roshini M. Ponnamperuma, Sa Ra Park, Steven Jay, Linan Ha, Wendy C. Weinberg. A role for c-Rel in ΔNp63α/v-RASHA-driven carcinogenesis?. [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 768. doi:10.1158/1538-7445.AM2013-768
Potential False-Positive Meckel Scan Due to Displaced Kidney Caused by Recurrent Retroperitoneal Teratoma
Authors: Tzu-Pei Su, Nai-Ming Cheng, Hui-Chieh Chuang, Chien-Cheng Chen, Chieh Lin
Journal: Clinical Nuclear Medicine (2013)

We report the findings of a Meckel scan in a 19-year-old patient treated for retroperitoneal teratoma with intermittent tarry stool for 1 month. Two focal stases of radioactivity in the right upper quadrant of the abdomen were noted. SPECT/CT for localization revealed that these 2 foci were within the displaced right kidney along with an adjacent bulky retroperitoneal mass. The patient subsequently underwent surgery, and histopathological studies confirmed recurrent teratoma. Two foci of increased radioactivity instead of 1 may have provided hints for the physiological characteristics of such lesions.
839 DEFER OR TREAT NOW? REASONS FOR THERAPEUTIC DECISIONS IN PATIENTS WITH CHRONIC HEPATITIS C GENOTYPE 1 IN THE EARLY ERA OF DIRECTLY ACTING ANTIVIRALS
Authors: J.M. Kittner, N. Weiss, J.M. Schattenberg, A. Grambihler, M.F. Sprinzl, F.R. Thieringer, J. Wiltink, S. Koch, A. Weinmann, P.R. Galle, M. Schuchmann
Journal: Journal of Hepatology (2013)
A Controlled Family Study of Live, Attenuated Rubella-Virus Vaccine
Authors: Lewis B. Lefkowitz, Robert R. Rafajko, Charles F. Federspiel, Robert W. Quinn
Journal: New England Journal of Medicine (1970)

In a family study of live, attenuated rubella-virus vaccine (HPV80), 85 susceptible placebo recipients were exposed to siblings with evidence of infection with the vaccine strain of rubella virus after inoculation. Of these placebo recipients a rise in titer of hemagglutination-inhibiting antibody developed in one. The type of antibody response and her clinical course indicated that vaccine virus infection had occurred. Although this response might have resulted from her having received vaccine by mistake, the possibility of intrafamilial spread of vaccine-strain virus must be seriously considered.
P473Expressional changes of matrix metalloproteinases -2 and -9 in abdominal aorta in patients with atherosclerosis
Authors: A Grigoryan, A Dimitrova, T Betova, S Tisheva, K Kostov, M Apostolova
Journal: Cardiovascular Research (2014)

Purpose: Matrix metalloproteinases -2 and -9 (MMP-2 and MMP-9) are representatives of the group of gelatinases that have similar effect, resulting in the degradation of collagen type IV. MMP-2 and MMP-9 have a key role in the pathogenesis of atherosclerosis. The aim of the present study was to determine the extent of the immunohistochemical expression of MMP-2 and MMP-9 in the vascular wall of the abdominal aorta in patients with atherosclerotic changes. Methods: We investigated by immunohistochemistry (polyclonal antibodies,class IgG, Santa Cruz Biotechnology, USA) the expressional changes of MMP-2 and MMP-9 in abdominal aorta obtained from autopsied cases. We used 5 nonatherosclerotic (control group - G1) and 20 atherosclerotic segments (group - G2) from human abdominal aorta. These arteries were colected at autopsy from 25 cases within 5 hours of death. Results: In the nonatherosclerotic aorta MMP-2 and MMP-9 were expressed mainly in the endothelium and the smooth muscle cells (VSMC) of the vascular wall. The expression of MMP-2 and MMP-9 was significantly increased (p<0.05) in the atheromatous plaques of atherosclerotic abdominal aorta in comparison with nonatherosclerotic. Intense expression of MMPs-2 in media
A Packaging Cell Line Generating CD4-Specific Retroviral Vectors for Efficient Gene Transfer into Primary Human T-Helper Lymphocytes
Authors: Sonja Thaler, Barbara S. Schnierle
Journal: Molecular Therapy (2001)

Murine leukemia virus (MuLV) can be pseudotyped with a variant of the human immunodeficency virus (HIV) envelope gene encoding the surface glycoprotein gp120-SU and a carboxy-terminally truncated transmembrane (TM) protein with only seven cytoplasmic amino acids. MuLV/HIV-1 pseudotyped retroviral vectors selectively target gene transfer to human cells expressing both CD4 and CXCR4. To apply this vector system to gene therapy of human diseases, we generated a stable packaging cell line, FLY-HIV-87, expressing the MuLV gag and pol genes and the C-terminally truncated variant of the HIV-1 envelope gene, but no retroviral vector genome. Production of infectious vector particles was tested after the introduction of different vector genomes and was in the range of 5x10(5) IU/ml. The vector particles could be concentrated up to 25-fold. Specific and efficient gene transfer into CD4/CXCR4 expressing cell lines and stimulated primary human CD4+ peripheral blood lymphocytes was achieved. Thus the packaging cell line FLY-HIV-87 is highly suitable for gene therapy of disorders of human T-helper cells.
The Secretory Small GTPase Rab27B Regulates Invasive Tumor Growth and Metastasis through Extracellular Heat Shock Protein 90α.
Authors: A. Hendrix, D. Maynard, P. Pauwels, G. Braems, H. Denys, R. Van den Broecke, S. Van Belle, V. Cocquyt, M. Bracke, M. Seabra, W. Gahl, O. De Wever, W. Westbroek
Journal: Cancer Research (2009)

Abstract Background: Vesicle exocytosis, controlled by secretory GTPases such as Rab27B, delivers critical pro-invasive factors into the tumor microenvironment. The biological role and expression status of Rab27B in breast cancer was unknown.Methods: Rab27B was studied in human breast cancer cells (MCF-7, T47D, ZR75.1) using GFP-fusion constructs, including Rab27A and Rab27B point mutants defective in GTP-binding or geranylgeranylation. In cell culture, cell-cycle progression was evaluated by flow cytometry and Western blotting, invasion was assessed using Matrigel and collagen type I substrates. Orthotopic tumor growth, local invasion and metastasis were analyzed in mouse xenograft models. Mass spectrometry was performed to identify Rab27B-secreted pro-invasive factors. Rab27B levels in clinical breast cancer were analyzed by quantitative reverse transcription-polymerase chain reaction (n=20) and immunohistochemistry (n=60). Statistical tests were two-sided.Results: Rab27B-upregulation promoted G1/S phase cell cycle transition, F-actin reorganization and invasion in cell culture, and invasive tumor growth and peritoneal metastasis in a xenograft mouse model (at 10 weeks, survival of MCF-7 GFP vs GFP-Rab27B injected mice was 100% vs 62.5%, P=0.0307). Proteomic analysis of purified Rab27B-secretory vesicles and the secretome of Rab27B-expressing breast cancer cells identified heat shock protein (HSP)90α as key pro-invasive factor. HSP90α secretion occurred in a Rab27B-dependent manner and was required for matrix metalloproteinase-2 activation. All Rab27B-mediated functional responses were GTP- and geranylgeranyl-dependent. In clinical samples, upregulation of endogenous Rab27B mRNA and protein correlated with lymph node metastasis (P=0.0002) and differentiation grade (P=0.0014) in estrogen receptor (ER)-positive human breast tumors.Conclusions: Rab27B, a new prognostic marker for ER-positive breast cancer, regulates invasive growth and metastasis. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 6144.
Pertinence des indications de la coloscopie dans le service d'hépato-gastroentérologie du centre hospitalier universitaire de Cocody: application des critères établis par l'European Panel on the Appropriateness of Gastrointestinal Endoscopy (EPAGE)
Authors: C Njomo Njossu, C Assi, L Nigue, A Ouattara, D Soro, A Coulibaly, E Allah-Kouadio, MJ Lohoues Kouacou, BM Camara
Journal: Endoscopy (2011)

Introduction: la coloscopie permet le diagnostic et la surveillance des polypes et des cancers colo-rectaux. Sa prescription doit être rationalisée tenant compte du rapport risque/bénéfice. Les critères de l'EPAGE permettent d'évaluer la pertinence des indications de la coloscopie (1). Aucune étude n'a évalué cette pertinence à Abidjan. L'objectif de notre étude était d'évaluer l'application en pratique clinique des critères de l' EPAGE, évaluer -sur la base de ces critères- la pertinence des indications de la coloscopie et rechercher une éventuelle corrélation entre la pertinence de l'examen et le résultat endoscopique et/ou histologique de celui-ci.
Abstract 1806: AP-1 transcriptionally regulates expression of miR-155 in colon cancer cells.
Authors: Benjamin C. Onyeagucha, Melania Mercado-Pimentel, Erik Flemington, Mark A. Nelson
Journal: Cancer Research (2013)

Abstract Accumulating evidence indicates elevated S100P promotes the pathogenesis of cancers, including colon cancer. S100P exerts its effects by binding to and activating the Receptor for Advance Glycation End-products (RAGE). The effects of up-regulated S100P/RAGE signaling on cell functions are well documented. Despite these overwhelming evidences, little is known about the downstream targets of S100P/RAGE signaling. In the present study, we demonstrated for the first time that activation of RAGE by S100P regulates oncogenic microRNA-155 (miR-155) expression through Activator Protein-1 (AP-1) stimulation in colon cancer cells. Both S100P and miR-155 expressions are up-regulated in colon tumor specimens. Ectopic S100P expression leads to elevation of miR-155 level. Conversely, knockdown of S100P results in a decrease in miR-155 levels. Exogenous S100P induces miR-155 expression, but blockage of the RAGE receptor with anti-RAGE antibody suppresses the induction of miR-155 by exogenous S100P. Attenuation Blockage of AP-1 activation by S100P, through pharmacological inhibition of MEK activation or genetic inhibition of c-Jun activation using dominant negative c-Jun (TAM67) suppresses miR-155 induction by exogenous S100P. Exogenous S100P treatment stimulates the enrichment of c-Fos, an AP-1 family member at the miR-155 promoter site. Finally, functional study shows that miR-155 knockdown decreases colon cancer cell cell cell growtholon formation and motilityotility in S100P stably transfected cells and parental cells. Taken together, these data demonstrate that the expression of miR-155 is regulated by S100P is dependent on RAGE activation and stimulation of AP-1. Furthermore, the results show that miR-155 is a downstream target of S100P/RAGE signaling and a critical player in S100P functions in colon cancer cells. Citation Format: Benjamin C. Onyeagucha, Melania Mercado-Pimentel, Erik Flemington, Mark A. Nelson. AP-1 transcriptionally regulates expression of miR-155 in colon cancer cells. [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 1806. doi:10.1158/1538-7445.AM2013-1806
Abstract 1799: Hypoxia-induced alterations of renal cell carcinoma cells and their modulation by tyrosine kinase inhibitors
Authors: Sandra Leisz, Susanne Erb, Franziska Leich, Anja Mueller, Barbara Seliger
Journal: Cancer Research (2012)

Abstract Renal cell carcinoma (RCC) is the most common neoplasm in the adult kidney and its incidence is increasing over the last 20 years. Unfortunately, approximately 30 % of patients are diagnosed at a metastatic stage, which is associated with a poor prognosis and a 5-year survival rate of &amp;lt; 10 %. The clear cell RCC, representing approximately 75 % of RCC lesions, is characterized by a frequent inactivation of the Von-Hippel-Lindau protein (pVHL) resulting in the upregulation of the hypoxia-inducible factor 1α (HIF-1α), which consequently induces the transcription of hypoxia-responsive genes, such as the vascular endothelial growth factor receptor (VEGF) thereby inducing angiogenesis. Thus, the inhibition of angiogenesis is a suitable tool for the therapy of advanced clear cell RCC. During the last decade agents targeting tumor angiogenesis include inhibitors of the VEGF receptor pathway and the mammalian target of rapamycin (mTOR) have been successfully applied for the treatment of this disease. Using proteome-based studies and microRNA arrays hypoxia-regulated miRs and proteins in VHL- versus VHL+ RCC have been identified in the absence or presence of the angiogenesis inhibitors sunitinib and axitinib. (i) A differential miR and protein expression profile exhibiting an inverse correlation was found upon hypoxia, which further differed in VHL- versus wild-type VHL RCC cells. (ii) The hypoxia-regulated miRs and proteins in these cell systems were altered by the tyrosine kinase inhibitors (TKI) sunitinib and axitinib treatment. (iii) Functional analysis of the hypoxia-regulated candidate biomarkers and their modulation by both TKI are currently performed. (iv) The differential expression pattern of miRs and proteins under hypoxia as well as in the absence and presence of both TKIs were confirmed by RT-PCR and Western blot analysis. These data were shown for the first time an effect of sunitinib and axitinib on hypoxia-induced alterations in RCC, which not only leads to a better understanding of the mechanisms of action of both TKIs, but also to the define of novel strategies for the targeted treatment of RCC. 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 1799. doi:1538-7445.AM2012-1799