tbuckley/cabot-search huggingface dataset:
AB0722 Ominous Prognosis of Secondary Amyloidosis in Patients with Spondyloarthropathies
Authors: S. Rodríguez-Muguruza, M. Martinez-Morillo, S. Holgado, A. Riveros-Frutos, J. Sanint, A. Prior, L. Mateo, J. Cañellas, X. Tena, A. Olive
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Secondary amyloidosis (AAa) is a disorder caused by deposition of insoluble amyloid A fibrils in different tissues and organs. It is a rare and serious complication of rheumatic diseases including spondyloarthropathies. <h3>Objectives</h3> The aim of this study was to determine the clinical features, laboratory data, treatment and clinical outcome of patients with spondyloarthropathies who developed AAa. <h3>Methods</h3> Design retrospective (1984-2013). Hospital: academic tertiary hospital. Referral area: 850.000 inhabitants. We reviewed the medical records of 1125 patients with spondyloarthropathies: 509 (45%) psoriatic arthritis (PsA), 263 (23%) ankylosing spondylitis (AS), 128 (11.3%) spondylitis associated with inflammatory bowel diseases (IBD), 190 (16.8%) undifferentiated spondyloarthropathy and 35 (3.1%) reactive arthritis diagnosed at our centre. We selected patients who had a histological diagnosis of AAa. <h3>Results</h3> Twelve (1.06%) patients with AAa were recruited: 10 (83%) males and 2 (16.6%) females. Five (41,6%) AS, 3 (25%) PsA, 3 (25%) spondylitis associated with IBD and 1 (8%) reactive arthritis. Mean age at AAa diagnosis: 55.75 years (interval 71-33 years). Amyloid deposits were observed on rectal biopsy (5 cases), kidney biopsy (3 cases) and subcutaneous fat biopsy (2 cases). In two cases the diagnosis was made incidentally (bladder and gallbladder). The mean age at spondyloarthropathy diagnosis was 32 years and the mean disease duration was 23.2 years. The mean values of erythrocyte sedimentation rate and C-reactive protein, at diagnosis of AAa, were 58.71mm and 35.47 mg/L respectively. AAa was suspected in 8 patients because of nephrotic-range proteinuria (2 patients), acute renal failure (5 patients) and diarrhea (1 patient). HLA B27 was positive in 6 patients, negative in 2. Five patients were treated with infliximab, 4 of whom because amyloidosis. Four patients underwent hemodialysis for end-stage renal disease, one of them died because complications directly related to renal failure. Four patients died of sepsis. <h3>Conclusions</h3> The frequency of clinical apparent AAa in our patients was 1.06% (12 patients). There was a marked male predominance. Clinical AAa was diagnosed at a relatively late stage in spondyloarthropathies. The predominant clinical picture was nephrotic syndrome. Prognosis was ominous. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.3143
Unusual Bone Scan of a Child with Osteogenesis Imperfecta
Authors: Yakup Yurekli, Serpil Erdogan, Emre Cullu
Journal: Clinical Nuclear Medicine (2003)

From the Departments of Nuclear Medicine* and Orthopeadics,†Adnan Menderes University, School of Medicine, Aydin, Turkey Received for publication May 1, 2002. Revision accepted August 16, 2002. Correspondence: Yakup Yurekli, Adu Tıp Fakültesi Nükleer Tıp AD, Aydin 09100, Türkiye. E-mail: [email protected]
Abstract 1708: Telomerase as an important target of androgen-signaling blockade for prostate cancer treatment
Authors: Shuang Liu, Yanfeng Qi, Yubin Ge, Tamika Duplessis, Brian G. Rowan, Helen Cheng, Paul S. Rennie, Haitao Zhang, Yan Dong
Journal: Cancer Research (2010)

Abstract As the mainstay treatment for advanced prostate cancer, androgen-deprivation therapy (ADT) targets the action of androgen receptor (AR) by reducing androgen level and/or by the administration of anti-androgen that competes with androgens for binding to AR. Albeit effective in extending survival, ADT is associated with dose-limiting toxicity and the development of castration-resistant prostate cancer (CRPC) after prolonged use. Since CRPC is generally lethal and incurable, developing effective strategies to enhance the efficacy of ADT and circumvent resistance becomes an urgent task. Continuous AR signaling constitutes one major mechanism underlying the development of CRPC. The present study showed that methylseleninic acid (MSA), an agent that effectively reduces AR abundance, could enhance the cancer-killing efficacy of the anti-androgen bicalutamide in both androgen-dependent and castration-resistant prostate cancer cells. We found that combination of MSA and bicalutamide produced a robust downregulation of prostate-specific antigen and a recently identified AR target, telomerase and its catalytic subunit, telomere reverse transcriptase (hTERT). The downregulation of hTERT occurs mainly at the transcriptional level, through reducing AR occupancy of the hTERT promoter. Furthermore, apoptosis induction by the two agents is significantly mitigated by restoration of hTERT. Our findings thus indicate that MSA in combination with anti-androgen could represent a viable approach to improve the therapeutic outcome of ADT. Given the critical role of hTERT/telomerase downregulation in mediating the combination effect and the fact that hTERT/telomerase could be measured in blood and urine, hTERT/telomerase could serve as an ideal tumor-specific biomarker to monitor the efficacy of the combination therapy non-invasively. (Supported by the Department of Defense Prostate Cancer Training grant No. W81XWH-08-1-0291 (SL); the National Cancer Institute grant No. K01 CA114252 (YD); the American Cancer Society grant No. RSG-07-218-01-TBE (YD)) 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 1708.
Abstract 4364: TR4 for the treatment of human neoplasms: Novel antiNotch agent
Authors: Agamemnon A. Epenetos, Spyros Kyprianou, Silvia Colucci, Christina Kousparou, Mahendra Deonarain
Journal: Cancer Research (2011)

Abstract It has been widely demonstrated that the Notch receptor signaling pathway is required for regulation and differentiation of stem cells in many tissues cell types. It is also well established that aberrant Notch signaling can lead to several human forms of cancer, including leukaemia, breast, colon, skin, cervical, and lung cancer, making Notch an attractive target for new cancer therapies. It has become clear that one of the major therapeutic targets in the Notch pathway is the cleavage of four Notch receptors, in which gamma-secretase inhibitors play a role. Unfortunately inhibition of γ-secretase complex is accompanied by many serious side effects. In order to avoid the side effects associated with γ-secretase inhibitors and achieve an improved therapeutic effect, a more selective Notch inhibition is desirable. We have genetically engineered a fusion protein, consisting of the Drosophila transcription factor Antennapedia (ANTP) and the truncated version of Mastermind-like (MAML) that behaves in a dominant negative (DN) fashion and inhibits the Notch transactivation complex. This fusion protein, (ANTP/DN-MAML) or TR4, has been tested for its ability to target tumor cells in vitro and in vivo. Our results indicate that targeting Notch signaling with the ANTP/DN-MAML (TR4) suppresses Notch activation, translocates into nucleus and inhibits tumor growth in mice, without significant organ or systemic toxicity. 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 4364. doi:10.1158/1538-7445.AM2011-4364
Abstract 4717: Lymphotoxins activate NF-κB-mediated inflammatory and survival pathways in head and neck squamous cell carcinomas.
Authors: Tsu-Fan Cheng, Xinping Yang, Jamie Coupar, Han Si, Steven Lee, Jialing Zhang, Carter van Waes, Zhong Chen
Journal: Cancer Research (2013)

Abstract Head and neck squamous cell carcinomas (HNSCC) are highly inflammatory and preferentially metastasize to lymph nodes (LN). HNSCC exhibit constitutively activated canonical and alternative NF-κB pathways, but the upstream signals activating these NF-κB pathways have not been well characterized. We hypothesized that immune regulatory cytokines Lymphotoxin (LT) α and β produced by tumor and/or LN cells could be critical in upstream signal activation of NF-κB in HNSCC. Although LTs and their receptors (LTβR and TNFR) are known to be expressed and produced by lymphocytes, we found that LTα and β, and their receptors LTβR and TNFR, are also expressed and produced in a subset of HNSCC cell lines and tumor tissue specimens, when compared with primary human oral mucosal cells. LTα activated both canonical and alternative NF-κB pathways, as indicated by induction of nuclear translocation of NF-κB subunits, RELA, cREL, RELB, p52 in a time dependent manner. In contrast, LTβ mainly activated the alternative NF-κB pathway, enhancing nuclear translocation of RELB and p52. In addition, LTβ-mediated gene expression was examined by Illumina bead microarray platform, and the top pathways of upregulated genes included NF-κB, immunoregulatory, inflammatory, and survival signaling pathways. Our data suggested that HNSCC expressed lymphotoxins and their receptors could be critical factors that contribute to the constitutively activated NF-κB, inflammatory and survival signaling previously implicated in HNSCC pathogenesis. Understanding of lymphotoxin-mediated cross-talk with these inflammatory and survival signaling pathways, could provide a missing link between the inflammation and tumorigenesis in the tumor microenvironment. Citation Format: Tsu-Fan Cheng, Xinping Yang, Jamie Coupar, Han Si, Steven Lee, Jialing Zhang, Carter van Waes, Zhong Chen. Lymphotoxins activate NF-κB-mediated inflammatory and survival pathways in head and neck squamous cell carcinomas. [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 4717. doi:10.1158/1538-7445.AM2013-4717
Abstract 4294: Differentiated colorectal cancer cells protect tumor-initiating cells from irinotecan
Authors: Benjamin L. Emmink, Winan J. van Houdt, Robert G. Vries, Frederik J.H. Hoogwater, Connie R. Jimenez, Hans Clevers, Inne H.M. Borel Rinkes, Onno Kranenburg
Journal: Cancer Research (2010)

Abstract Normal colon tissue stem cells drive tissue turnover by generating daughter stem cells and a rapidly proliferating pool of progenitor cells that give rise to differentiated cell types with specialized functions. This functional hierarchy is preserved in colon tumors in which a tumor-initiating cell (or cancer stem cell) compartment drives the formation of proliferating and differentiated cell types with reduced tumorigenic potential. Normal colon stem cells possess a variety of resistance mechanisms that allow them to endure a lifetime of genotoxic insults. By inheriting these traits, tumor-initiating cells (TIC) are thought to be endowed with an intrinsic resistance to chemotherapy. However, the relationship between chemo-resistance and tumor-initiating potential in colon tumors is poorly understood. We studied this relationship using a series colonosphere cultures isolated from freshly resected primary colon tumors and liver metastases. These cultures are highly enriched for TIC, based on their high clone and tumor-forming potential and expression of the stem cell marker ALDH1. The TIC-enriched cultures display resistance to the toposomerase I inhibitor irinotecan. However, drug resistance is mediated by a small subpopulation of non-tumorigenic differentiated ALDH1-negative cells expressing the drug efflux pump ABCB1. ABCB1 is localized to the brush border of cells at the colonosphere periphery and of cells forming intra-spheroid tubules. In human colorectal liver metastases ABCB1 is predominantly localized to the luminal side of differentiated tubule-forming cells. These ABCB1 drug-resistant cells are proliferation-competent but unable to initiate tumor formation. Conversely, tumor-initiating cells are ABCB1-negative and drug-sensitive, but could generate non-tumorigenic drug-resistant offspring in vitro and in tumor xenografts. Our work shows that colorectal tumor-initiating cells do not display intrinsic resistance to irinotecan, most likely because they are derived from a normal stem cell population that does not express ABC transporters. Tumor-initiating cells generate a protective shield of drug-resistant ABCB1-positive offspring. Furthermore, the preservation of tumor-initiating capacity following irinotecan exposure requires the cooperative action of drug-sensitive tumor-initiating cells and their drug-resistant differentiated offspring. 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 4294.
<i>Notes from the Field</i>: Thyrotoxicosis After Consumption of Dietary Supplements Purchased Through the Internet — Staten Island, New York, 2015
Authors: Angela Regina, Nima Majlesi
Journal: MMWR Morbidity and Mortality Weekly Report (2016)

On June 18, 2015, a woman aged 30 years was brought to the Staten Island University Hospital Emergency Department (ED) in New York by her mother, who reported that the patient had become acutely confused at home, was repeating herself, and did not recognize her family members. She had a diagnosis of bipolar disorder for which she took lithium, and she had a history notable for polysubstance abuse (use of three or more addictive drugs in the past 12 months). Her other medications included risperidone (an antipsychotic), benztropine (an anticholinergic), and bupropion (an antidepressant). ED staff members learned from the patient's mother that the patient had started taking "diet pills" that contained a thyroid hormone, which the patient had purchased through the Internet 2 weeks earlier. The patient volunteered that she had doubled the dosage 1 week earlier, in an attempt to lose more weight.
290 THE INTERACTION BETWEEN NF-κB ACTIVATION AND PPARg ACTIVATION IS REGULATED BY Cks1–Skp2–p27(kip1) PATHWAY AND MEDIATES TUMOR PROGRESSION IN HUMAN HEPATOCELLULAR CARCINOMA
Authors: S. Maeda, S. Kuboki, H. Shimizu, K. Shinoda, H. Yoshidome, M. Ohtsuka, A. Kato, H. Yoshitomi, K. Furukawa, T. Takayashiki, D. Okamura, D. Suzuki, M. Nakajima, T. Aida, M. Miyazaki
Journal: Journal of Hepatology (2013)
Gut Microbiota, the Genome, and Diet in Atherogenesis
Authors: Joseph Loscalzo
Journal: New England Journal of Medicine (2013)

The Galtonian distinction between the influence of genetics and environment on phenotype is now widely recognized as an overly simplistic dichotomy. Genes and environmental factors interact in myriad ways to modulate and modify the biology of all living organisms, challenging the notion that these two principal determinants of phenotype can ever truly act independently of each other. Environmental exposures and experiences can have a direct influence on the expression of genes through epigenetic processes or on the function of gene products through post-translational modification. Likewise, genetic factors influence the consequences of environmental exposures or stresses on the organism.Dietary substances . . .
COMPLICACIONES POSTERIORES A LA COLANGIO-PANCREATOGRAFÍA RETRÓGRADA ENDOSCÓPICA EN PACIENTES CON CIRROSIS HEPÁTICA
Authors: C Leal, O Sendino, A Fernández-Simon, JM Bordas, G Fernández-Esparrach, M Pellisé, M López-Ceron, C Rodriguez D Miguel, A Ginés, J Llach, A Cárdenas
Journal: Endoscopy (2013)

Introducción: Las complicaciones posteriores a la CPRE en la población general y en algún subgrupo de pacientes han sido ampliamente evaluadas. Sin embargo, existe poca información en los pacientes con cirrosis. Objetivo: Determinar la tasa y tipo de complicaciones post-CPRE así como evaluar los factores que se asocian a complicación en los pacientes con cirrosis. Material y Método: Análisis retrospectivo de las CPRE diagnósticas y/o terapéuticas realizadas en un hospital de tercer nivel sobre pacientes con cirrosis entre los años 2002 – 2012. Se evalúa la historia clínica del paciente y las variables demográficas, del procedimiento y las complicaciones observadas hasta el séptimo día. Resultados: Se analizan 85 procedimientos sobre un total de 72 pacientes con cirrosis (Child A, 28; Child B, 43; Child C, 14). Se practicó esfinterotomía y/o precorte en el 70% (N = 60). Las complicaciones ocurrieron en 12 procedimientos (14,1%): hemorragia en 6 pacientes (7%), pancreatitis en 3 (3,5%), colangitis en 3 (3,5%) y ninguna perforación. Todas fueron leves excepto un caso grave de hemorragia. La mortalidad fue nula. El factor de riesgo principal asociado al desarrollo de complicaciones fue la realización de esfinterotomía endoscópica (12/12;100% vs. 43/73;59%; P = 0.03). La función hepática avanzada, las descompensaciones y el número de plaquetas no se asociaron a más complicaciones (P = 1;P = 0.7;P = 0.8, respectivamente). Conclusiones: La tasa de complicaciones fue del 14%, fundamentalmente en forma de hemorragia. Los factores de riesgo en esta serie se relacionan con la técnica pero no con las características propias del paciente con cirrosis.
Abstract 5023: CpG pethylator phenotype (CIMP) methylation pattern in Puerto Ricans Hispanics colorectal cancer patients
Authors: Mercedes Y. Lacourt, Jeyshka Reyes, María E. Lozada, Heriberto M. Rodriguez, Xiomara Castillo, Alberto Cardona, Raúl D. Bernabe, Marcia Cruz-Correa
Journal: Cancer Research (2012)

Abstract Introduction: The CpG island methylator phenotype (CIMP), characterized by extensive promoter methylation, seems to be a distinct epigenotype of colorectal cancer (CRC). CIMP hypermethylation blocks transcriptional activation of several genes associated with tumor suppression, cell cycle, DNA repair, differentiation and apoptosis. Moreover, CIMP hypermethylation is an important epigenetic change associated with gene silencing, poor prognosis and lower response to chemotherapy in CRC patients. However, prevalence of CIMP status and specific clinicopathological features has not been examined in Puerto Rican Hispanic CRC patients. In this study, we determined the CIMP status in PR Hispanics with CRC and examined its association with phenotypical characteristics. Methods: Methylation-specific PCR (MSP) was used to evaluate DNA methylation in eight CIMP-specific promoters (CACNA1G, IGF2, NEUROG1, RUNX3, SOCS1, hMLH 1, CRABP1 and p16) gene in eighty-nine CRC cases. No-CIMP status was defined as the absence of methylation, CIMP-Low status as one to four methylated loci, and CIMP-High status as five or more methylated loci. Clinicopathological characteristics were correlated with CIMP status using Wilcoxon rank tests, Chi square and Fisher exact t-tests, as appropriate using STATA 10.0. Results: Eighty-nine CRC cases (mean age at diagnosis 60.5 ± 10.3 years; 49 males) were evaluated. Tumors were mostly located in the distal colon (71.0%). The 5.6 percent (5/89) of CRC cases were CIMP-High, 88% (87.6/89) were CIMP-Low, and 6.7% (6/89) were No-CIMP. CRABP1 (69.7%), IGF2 (48.3%) and p16 (43.8%) were the three most commonly methylated genes. CIMP-High/Low tumors were more common among women and among individuals ≥ 60 y/o (borderline statistical significance). There were no significant statistical associations between CIMP status and tumor staging, differentiation, tumor location or survival. Discussion: We report the CIMP status in Puerto Rican Hispanics with CRC. CIMP-hypermethylation may be less frequent among Hispanics than previously reported in other racial and/or ethnic groups, with a discrete clinicopathological phenotype and gene methylation pattern. A comprehensive understanding of the differences in epigenetic silencing of promoter regions by hypermethylation will shed light on the mechanisms resulting in colorectal tumorigenesis in Hispanic patients. Current efforts are underway to characterize a large number of Puerto Rican Hispanics CRC patients which may help tailor screening and therapeutic strategies for this population. 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 5023. doi:1538-7445.AM2012-5023
A6.20 Ectopic lymphoid neogenesis is strongly associated with activation of the IL-23 pathway in rheumatoid synovitis
Authors: N Yeremenko, R Celis, I Blijdorp, J Ramírez, JL Pablos, R Sanmartí, JD Cañete, DL Baeten
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background and objectives</h3> The functional relevance of synovial ectopic lymphoid neogenesis (ELN) in rheumatoid arthritis (RA) remains unknown. As ELN correlates with the degree of tissue inflammation we investigated whether ELN was associated with specific cytokine profiles. <h3>Materials and methods</h3> Paired synovial tissue (ST) (n = 63) and fluid (SF) (n = 44) was obtained from the inflamed knee joints of RA patients. Synovial inflammation and ELN was determined by immunohistology. CD21L was used as molecular marker of ELN. Cytokine expression was determined by ELISA and quantitative PCR in SF and ST, respectively. <h3>Results</h3> 48% of ST displayed ELN by histology. ELN+ samples had increased T and B lymphocyte infiltration (p &lt; 0.001) and CD21L expression (p = 0.014). SF analysis showed higher expression of IL-23 (p = 0.018) and IL-17F (p = 0.028) in ELN+ versus ELN- samples, with a similar trend for IL-22 (p = 0.070). Other cytokines, including IL-17A, IL-6, TNF-a, Th1 cytokines and Th2 cytokines, were not different. In ST, IL-23 (p = 0.030) mRNA levels were increased in ELN+ samples. Moreover, CD21L expression as molecular marker of ELN correlated significantly with mRNA expression of IL-23 (r = 0.70), IL-17F (r = 0.42), IL-21 (r = 0.30) and IL-22 (r = 0.33), but not IL-17A. The strong correlation between CD21L and IL-23, IL-17F, IL-21 end IL-22 was confirmed in an independent RA ST sample set (n = 36). IFNg and IL-2, but not IL-6 and TNF-α, also showed some correlation with CD21L expression. <h3>Conclusion</h3> Synovial ELN in RA is strongly associated with increased expression of IL-23/IL-17-related cytokines. Whether patients depicting synovial ELN respond differently to therapeutic targeting of this pathway remains to be determined.
632 AETIOLOGY OF CHRONIC LIVER DISEASE INFLUENCES CLINICAL PRESENTATION AND OUTCOME OF HEPATOCELLULAR CARCINOMA: A SINGLE CENTER COHORT STUDY
Authors: F. Oliveri, C. Rastelli, P. Colombatto, B. Coco, P. Ciccorossi, V. Romagnoli, B. Cherubini, R. Lencioni, L. Crocetti, C. Bartolozzi, A. Campatelli, F. Filipponi, F. Bonino, M.R. Brunetto
Journal: Journal of Hepatology (2013)
RISK FACTORS FOR MORTALITY IN PEDIATRIC CARDIAC INTENSIVE CARE UNIT PATIENTS MANAGED WITH EXTRACORPOREAL MEMBRANE OXYGENATION IN A CONTEMPORARY COHORT
Authors: Barbara-Jo Achuff, Matthew D. Elias, Matthew J. O’Connor, Richard F. Ittenbach, Chitra Ravishankar, Susan C. Nicolson, Thomas L. Spray, Stephanie Fuller, J. William Gaynor
Journal: Journal of the American College of Cardiology (2016)