tbuckley/cabot-search huggingface dataset:
PML-RAR alpha induces the downmodulation of HHEX: a key event responsible for the induction of an angiogenetic response
Authors: Ernestina Saulle, Alessia Petronelli, Elvira Pelosi, Elena Coppotelli, Luca Pasquini, Ramona Ilari, Francesco Lo-Coco, Ugo Testa
Journal: Journal of Hematology & Oncology (2016)

Recent studies indicate that angiogenesis is important in the pathogenesis of acute myeloid leukemias (AMLs). Among the various AMLs, the bone marrow angiogenetic response is particularly pronounced in acute promyelocytic leukemia (APL). However, the molecular mechanisms responsible for this angiogenetic response are largely unknown. In the present study, we have explored the role of HHEX, a homeodomain transcription factor, as a possible mediator of the pro-angiogenetic response observed in APL. This transcription factor seems to represent an ideal candidate for this biologic function because it is targeted by PML-RARα, is capable of interaction with PML and PML-RARα, and acts as a regulator of the angiogenetic response.We used various cellular systems of APL, including primary APL cells and leukemic cells engineered to express PML-RARα, to explore the role of the PML-RARα fusion protein on HHEX expression. Molecular and biochemical techniques have been used to investigate the mechanisms through which PML-RARα downmodulates HHEX and the functional consequences of this downmodulation at the level of the expression of various angiogenetic genes, cell proliferation and differentiation.Our results show that HHEX expression is clearly downmodulated in APL and that this effect is directly mediated by a repressive targeting of the HHEX gene promoter by PML-RARα. Studies carried out in primary APL cells and in a cell line model of APL with inducible PML-RARα expression directly support the view that this fusion protein through HHEX downmodulation stimulates the expression of various genes involved in angiogenesis and inhibits cell differentiation.Our data suggest that HHEX downmodulation by PML-RARα is a key event during APL pathogenesis.
FRI0081 Titers of Anti-Ccp Antibodies, IL-6, Tnf-Alpha and CRP Are Associated with Increased Carotid Intima-Media Thickness: Cross-Sectional Analysis of A Rheumatoid Arthritis Group without Cardiovascular Risk Factors
Authors: M. Vazquez Del Mercado, L. Nuñez Atahualpa, M. Figueroa Sanchez, E. Gomez, A.D. Rocha Muñoz, B.T. Martín-Márquez, E. Corona Sanchez, E. Martínez García, R. Navarro Hernandez, J. Aguilar Arreola, L. Gόnzalez Lόpez, J.I. Gámez Nava, A. Bernard Medina, A. Nuñez-Atahualpa, J. Andrade-Garduño, R. Vargas-Ramírez
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> The main causes of death in Rheumatoid Arthritis (RA) are cardiovascular events related to early atherosclerosis, myocardial infarction and congestive heart failure. The risk for cardiovascular disease it it not completely explained by the traditionally accepted cardiovascular risk factors. Inflammatory pathways of RA might be involved in the pathogenesis of subclinical atherosclerosis. <h3>Objectives</h3> To evaluate the relationship of anti-CCP antibody titers, serum IL-6, TNFa and high sensitivity c-Reactive Protein with increased carotid intima-media thickness (cIMT) in patients with RA without cardiovascular risk factors. <h3>Methods</h3> Sixty patients with RA, 27 anti-CCP positive and 33 anti-CCP negative, and 62 controls (HC) matched by age and gender. All groups were assessed for comorbidities, demographics, clinical evaluations, and cardiovascular risk calculated by atherogenic index of plasma (AIP). The cIMT was performed by high-resolution B-mode ultrasound by a single operator. Serum titers of anti-CCP, hs-cRP, levels of TNFα and IL-6 were measured by ELISA. <h3>Results</h3> The anti-CCP positive RA patients showed increased cIMT compared to HC and anti-CCP negative patients (p&lt;0.001). Anti-CCP positive vs. Anti-CCP negative patients, had increased disease activity (DAS28) (p=0.05), increased AIP (p&lt;0.001), higher TNFα (20.54±5.38 vs 32.77±12.30, p=0.002) and IL-6 (18.54±14.09 vs 65.07±34.95, p&lt;0.001). The cIMT correlated with titers of anti-CCP (r=0.539, p&lt;0.001), TNFα (r=0.791, p&lt;0.001) and IL-6 (p=0.794, p&lt;0.001). In multiple regression analysis, cIMT was associated with hs-cRP (p=0.05) and anti-CCP levels (p=0.006). <h3>Conclusions</h3> High levels of anti-CCP and hs-cRP are useful markers of an increased cIMT and cardiovascular risk supporting a clinical role of the preventive measurement of cIMT in RA <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.5947
67 TELAPREVIR WITH ADJUSTED DOSE OF RIBAVIRIN IN NAIVE CHC-G1: EFFICACY AND TREATMENT IN CHC IN HEMODIALYSIS POPULATION. TARGET C (RCT)
Authors: P.P. Basu, R. Siriki, N.J. Shah, S. Farhat, K. Mittimani, S. Atluri, M. Rahaman, R.S. Brown
Journal: Journal of Hepatology (2013)
LUNG ULTRASOUND FOR THE EVALUATION OF PULMONARY CONGESTION IN HEART FAILURE OUTPATIENTS: A COMPARISON WITH CLINICAL ASSESSMENT, NATRIURETIC PEPTIDES AND ECHOCARDIOGRAPHY
Authors: Marcelo Haertel Miglioranza, Luna Gargani, Roberto Sant'Anna, Marciane Rover, Vitor M. Martins, Augusto Mantovani, Cristina Weber, Maria Antonieta Moraes, Carlos Jader Feldman, Eugenio Picano, Rosa Sicari, Renato Kalil, Tiago Leiria
Journal: Journal of the American College of Cardiology (2013)
AB1021 Sonographic Semi-Quantitative Evaluation of the Shoulder Synovitis in Polymyalgia Rheumatica and Elderly-Onset Rheumatoid Arthritis Mimicking Pmr
Authors: T. Suzuki, A. Okamoto
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Through the clinical experience of the ultrasound examination of the shoulder lesions in untreated patients with polymyalgia rheumatica (PMR) and elderly-onset rheumatoid arthritis mimicking PMR (polymyalgic-EORA), we noted that there seems to be differences not in the kind or the frequency but in the degree of synovial inflammation between the two diseases. <h3>Objectives</h3> To compare the severity of the shoulder syonvitis between PMR and polymyalgic-EORA using semi-quantitative ultrasound evaluation. <h3>Methods</h3> We analyzed consecutive records of 14 PMR patients and 14 polymyalgic-EORA patients in our hospital between 2010 and 2012, in whom adequate grey-scale (GS) and power Doppler (PD) ultrasound images of both shoulders before treatment-start were available. The severity of tenosynovitis of the long-head of the biceps (LHB), bursitis of shoulder including subdeltoid, subacrominal and subcoracoid bursitis, and joint synovitis of grenohumeral joint (GHJ) were subjectively graded and scored for GS and PD on a four-point scale: 0 = absent, 1 = mild, 2 = moderate or 3 = severe. <h3>Results</h3> There was a tendency that shoulder synovitis in PMR was milder than that in polymyalgic-EORA. There were statistically significant differences in the PD-grade of LHB, GS-grade of bursitis and GS-grade of GHJ by chi-square test. There was also a significant difference in GS-score of bursitis (1.18±1.28 vs 0.36±0.56, p=0.004), PD-score of bursitis (1.00±1.22 vs 0.36±0.73, p=0.021) and the sum of the 3 GS- and 3 PD-scores (6.43±5.45 vs 4.29±2.51, p=0.046) (mean ± SD, polymyalgic-EORA vs PMR) by Welch9s <i>t</i>-test. <h3>Conclusions</h3> Sonographic semi-quantitative assessment revealed that shoulder synovitis in PMR tends to be milder than that in elderly-onset RA mimicking PMR. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.1419
Abstract 1100: p53 blocks TGFβ-induced breast cancer metastasis by downregulating angiopoietin-like 4
Authors: Selvakumar Elangovan, Puttur D. Prasad, Vadivel Ganapathy, Muthusamy Thangaraju
Journal: Cancer Research (2010)

Abstract Transforming growth factor β1 (TGFβ1) is a multifunctional growth factor with a complex dual role in tumorigenesis. During the early stages of tumor formation, TGFβ1 acts as a tumor suppressor by inhibiting proliferation and inducing apoptosis in tumor cells. In advanced stage of cancer, many tumor cells become unresponsive to the growth-inhibitory actions of TGFβ1 and become more motile, more invasive, and resistant to apoptosis. The molecular mechanism responsible for the conversion of TGFβ1-associated tumor suppression into TGFβ1-associated pro-oncogenic and pro-metastatic signaling is not known. Thus, identification of the signaling pathway responsible for this process would have a potential impact in developing novel breast cancer therapy. Recent studies have shown that TGFβ1 induces ANGPTL4 expression, which leads to lung metastasis of breast cancer through disruption of the endothelial barrier. ANGPTL4, also known as fasting-induced adipose factor (FIAF), is a circulating protein; it plays a role in adipogenesis, angiogenesis, carcinogenesis and metastasis. The expression of ANGPTL4 is dramatically induced in human metastatic breast cancer cell line MB231 by TGFβ1. While studying the molecular mechanisms that control the TGFβ1-associated ANGPTL4 induction, we found that p53 functions as a potent negative regulator of TGFβ1 dependent induction of ANGPTL4 expression. In human breast cancer cells, TGFβ1 induces ANGPTL4 expression only in p53-null cell lines like MB453 and MB468, and in cell lines which express non-functional p53 like T47D and MB231. TGFβ1 is unable to induce ANGPTL4 expression in cells expressing the functional p53. To identify the mechanism by which p53 inhibits ANGPTL4 expression, we cloned 2.2 kb human ANGPTL4 promoter fragment into luciferase (pGL3-Luc) and GFP (pU3RII-pEGFP) reporter plasmids, and we used these constructs for reporter assays in p53 inducible (p53-Tet-On) MB453 cell line. The results showed that functional expression of p53 in MB453 cells effectively blocks the ability of TGFβ1 to induce the transcriptional activation of ANGPTL4, and suggest that p53 serves as a molecular dictator to block the tumor-suppressive and pro-metastatic actions of TGFβ in breast tissue. These studies describe the molecular processes involved in the regulation of ANGPTL4 expression in breast cancer, and will be helpful in the design and development of novel therapeutic strategies for the treatment of breast cancer. 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 1100.
Pseudogene Evolution in Drosophila Suggests a High Rate of DNA Loss
Authors: D. A. Petrov, Y-C Chao, E. C. Stephenson, D. L. Hartl
Journal: Molecular Biology and Evolution (1998)

Pseudogenes-nonfunctional copies of functional genes-are very common in mammals, with many genes having tens or even hundreds of pseudogene copies (Weiner, Deininger, and Efstratiadis 1986), yet they are exceedingly rare in Drosophila, for which very few putative pseudogenes have ever been reported (Jeffs and Ashburner 1991).In addition, some Drosophila sequences originally described as pseudogenes (Jeffs and Ashburner 1991;Sullivan et al. 1994) were later demonstrated to be novel functional genes (Long and Langley 1993;Begun 1997).Nevertheless, despite the rarity of bona fide pseudogenes in Drosophila, its genome does harbor some nonfunctional sequences that appear to be unconstrained by selection and that evolve much like pseudogenes.One of the clearest examples of such DNA are the so-called ''dead-on-arrival'' (DOA) copies of non-LTR retrotransposable elements.These copies are generated frequently as by-products of transposition of active non-LTR elements.They lack 5Ј sequences, including promoters and parts of open reading frames of proteins essential for transposition, and therefore they are usually predicted to evolve essential as pseudogenes.Recently, we were able to assess this prediction directly for at least one particular non-LTR element, Helena, in the Drosophila melanogaster and the Drosophila virilis species groups.Our approach relied on using maximum parsimony to separate the evolution of individual DOA insertions of Helena from the evolution of active lineages, which allowed us to demonstrate a lack of purifying selection acting on individual DOA elements (Petrov, Lozovskaya, and Hartl 1996; Petrov andHartl 1997, 1998).The pattern of spontaneous substitutions observed in these unconstrained DOA sequences yielded a surprising result.We discovered a striking asymmetry in the pattern of spontaneous length substitutions.Not only were deletions found to outnumber insertions almost 9 to 1, but deletions were also much larger on average, ranging in size from 1 to 432 bp, with an average of 25 bp, while insertions ranged from 1 to 7 bp, with a mean of 2.8 bp.The preponderance of long deletions in DOA copies of Helena leads to very rapid loss of DNA from these sequences, more than 60-fold higher than that ob-
Axonal Transection in the Lesions of Multiple Sclerosis
Authors: Bruce D. Trapp, John Peterson, Richard M. Ransohoff, Richard Rudick, Sverre Mörk, Lars Bö
Journal: New England Journal of Medicine (1998)

Multiple sclerosis is an inflammatory demyelinating disease of the central nervous system and is the most common cause of neurologic disability in young adults. Despite antiinflammatory or immunosuppressive therapy, most patients have progressive neurologic deterioration that may reflect axonal loss. We conducted pathological studies of brain tissues to define the changes in axons in patients with multiple sclerosis.
Are Drugs From the Jungle Cheaper to Develop?
Authors: J. Randal
Journal: JNCI Journal of the National Cancer Institute (1995)

Journal Article Are Drugs From the Jungle Cheaper to Develop? Get access Judith Randal Judith Randal Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 87, Issue 10, 17 May 1995, Pages 715–717, https://doi.org/10.1093/jnci/87.10.715 Published: 17 May 1995
Abstract 3953: C-Kit and Mitf signaling: Novel involvement of the PI3K/Akt and p38 pathways
Authors: Bengt Phung, Alexander Schepsky, Eirikur Steingrimsson, Lars Rönnstrand
Journal: Cancer Research (2010)

Abstract The development of melanocyte from melanoblast is regulated by the tyrosine kinase receptor c-Kit and the basic-helix-loop-heliz-leucine zipper transcription factor Mitf. It is established that Mitf activity is controlled by c-Kit activation and subsequent phosphorylation of the Erk/Mapk pathway. Serine phosphorylation (activation) of Mitf not only leads to upregulation of Mitf target gene expression but also ubiquitin dependent proteosomal degradation of Mitf. There is little knowledge surrounding the dysregulation between c-Kit and Mitf signaling that is often found in melanocyte progression to melanoma. The aim of our study is, therefore, to identify the signal transduction pathways involved in c-Kit mediated regulation of Mitf. In our study, we found c-Kit tyrosine phosphorylation sites and novel signaling pathways involved in the regulation of Mitf. Phosphorylation of c-Kit at Tyr721 has been shown to activate the PI3K pathway and Tyr568 and Tyr568/570 are responsible for Src kinase mediated activation of Erk/Mapk pathway. We demonstrate that Y721F, Y568F and Y568/570F mutation of c-Kit prevented Mitf mobility shift, indicating that these tyrosine phosphorylation sites are involved in Mitf regulation. Further, we observe that treatment of c-Kit and Mitf transfected HEK293T cells with LY294002 (PI3K inhib.), Akt IV (Akt inhib.), SU6656 (Src kinase inhib.), SB203580 (p38 inhib.) or U0126 (Mek inhib.) prevented c-Kit mediated Mitf mobility shift. Similar results were also observed in the murine melanocyte, Melan- A cell line where Mitf and c-Kit are endogenously expressed. In order to further verify c-Kit's role as Mitf regulator, we examined tyrosinase (downstream target of Mitf) promoter activity using a luciferase reporter construct. Ligand stimulation of c-Kit increased the Mitf target promoter activity. In conclusion, for the first time, we demonstrate that the signal transduction between c-Kit and Mitf is dependent on, 1) c-Kit Tyr721/PI3K/Akt pathway, 2) p38 pathway and 3) c-Kit Tyr568 or Tyr568/570 / Src kinase mediated Erk pathway. C-Kit activation leading to downstream were also shown to promote the transcriptional activity of Mitf. Our results reveal novel mechanisms by which c-Kit signaling regulates Mitf, with implication for understanding of both melanocyte development and melanoma. 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 3953.
AB0725 Ankylosing Spondylitis in Women, Clinical Features
Authors: S. Lapshina, L. Myasoutova, R. Mukchina
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Objectives</h3> To evaluate the clinical features and course of ankylosing spondylitis (AS) in women according to the City rheumatological center in Kazan. <h3>Methods</h3> The study involved two groups of patients with AS: 23 women and 25 men, respectively, matched by age (average - 33,1±9,6 years), established diagnosis (average - 3,4±1,6 years). The presence of inflammatory back pain (IBP), BASDAI, ASDAS, BASFI indexes, presence of HLA B27, the results of X-ray of the sacroiliac joint were evaluated. <h3>Results</h3> In women, the disease duration from first symptoms to diagnosis was 4,6±1,8 years, age at onset 26,3±4,9 years, in men these figures were 5,7±2,1 years and 25.6±3,8 years respectively. According to a survey of patients, disease onset in women was characterized by the presence of IBP (at 69.6%), occurring periodically (38.5%), peripheral arthritis clinic (60.9%), enthesitis (21, 7%), uveitis (4.3%). Among men IBP occurred in 60%, less recurring (14%), arthritis occurred in 40%, enthesitis - 75%, uveitis - 8%. At the time of examination in women peripheral arthritis was significantly (at 69.6%, p&lt;0.01) more common than in men (30.4%). Disease activity (BASDAI, ASDAS) were comparable in two groups. Functional impairment was higher in men (BASFI=5,6±1,2) than in women group (BASFI=4,5±1,0). According to the results of X-ray stage 0-1 sacroiliitis detected in 17.4% of women and 12% of men, the second stage - in 47.8% of women and 44% of men, the third stage - in 34.8% and 36% respectively, the fourth stage - 8% of men. <h3>Conclusions</h3> AS in women has several significant features: IBP at onset of the disease is less common and is less permanent, more often peripheral joints are involved, enthesitis and uveitis are rarely diagnosed. AS in women is characterized by slower radiological progression. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.3759
Autologous bone marrow transplantation reduces relapse in acute myeloid leukaemia
Authors: S. Mayor
Journal: BMJ (1998)

The largest trial ever carried out in acute myeloid leukaemia has found that autologous bone marrow transplantation after conventional chemotherapy reduces the risk of relapse by one third.

The trial, which was funded by Britain's Medical Research Council, included 381 patients aged up to 56 years who had acute myeloid leukaemia ( Lancet 1998; 351:700-8). They were given three courses of chemotherapy before their bone marrow was collected and frozen. After the next course of chemotherapy they were randomly assigned to two groups: one received no further treatment and the other received autologous bone marrow transplants.

Only 64 (37%) of the 190 patients in the group that received bone marrow transplants had a relapse compared with 101 (58%) of the 191 who received no further treatment. Over half (54%) of the group who …
Cigarette Smoking and Coronary Heart Disease
Authors: Joseph T. Doyle, Thomas R. Dawber, William B. Kannel, A. Sandra Heslin, Harold A. Kahn
Journal: New England Journal of Medicine (1962)

ALTHOUGH the importance of cigarette smoking in causing lung cancer is disputed1 , 2 mortality from all causes is substantially increased in heavy cigarette smokers.3 4 5 Most of the excess mortality is due to coronary heart disease, particularly in the American experience. With the exception of the reports from the Albany Cardiovascular Health Center and the Framingham Study6 , 7 reliable information relating morbidity from coronary heart disease to the use of tobacco has not yet been published. The data from both studies have suggested that a relation exists, but the populations studied have been too small and the follow-up period too short to permit . . .
Senate Moves to Restore Most NIH Funds
Authors: D. Tisevich
Journal: JNCI Journal of the National Cancer Institute (1995)

Journal Article Senate Moves to Restore Most NIH Funds Get access Dotty Tisevich Dotty Tisevich Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 87, Issue 13, 5 July 1995, Page 960, https://doi.org/10.1093/jnci/87.13.960 Published: 05 July 1995
Oculopharyngeal Muscular Dystrophy
Authors: Maurice Victor, Robert Hayes, Raymond D. Adams
Journal: New England Journal of Medicine (1962)

IN 1915 Professor E. W. Taylor1 called attention to an unusual familial form of dysphagia with ptosis of the eyelids. These symptoms were slowly progressive, leading eventually to death by starvation. Taylor contended, after the customary search of the medical literature, that the disease had not previously been described and that the constancy of the clinical picture "justifies its classification as a clinical entity."Even a cursory survey of earlier neurologic writings uncovers the fact that Taylor was not the first to note the familial occurrence of a restricted paralysis of cranial muscles. As early as 1879 Hutchinson2 had written . . .
Sphingolipids and Susceptibility to Asthma
Authors: Bruce D. Levy
Journal: New England Journal of Medicine (2013)

The most highly replicated asthma susceptibility locus, chromosome 17q21, houses three genes, one of which encodes ORMDL3, a protein that can inhibit the production of sphingolipids. Decreased sphingolipid synthesis disrupts magnesium homeostasis and increases airway hyperreactivity — a major diagnostic criterion for asthma.