tbuckley/cabot-search huggingface dataset:
Abstract 1714: A novel NPM-BAX pathway regulates death evasion and drug sensitivity in human hepatoma cells.
Authors: Sen-Yung Hsieh
Journal: Cancer Research (2013)

Abstract Death evasion is crucial for both carcinogenesis and resistance to anticancer therapies. Recently we identified nucleophosmin (NPM) as a key factor counteracting death stimuli in human hepatocellular carcinoma (HCC) cells. Here we report the identification of a novel NPM-BCL2-associated X protein (BAX) pathway orchestrating death evasion in human HCC cells. Silencing of NPM expression significantly sensitized HCC cells, particularly those bearing inactivated p53 (Huh7, Hep3B, and Mahlavu), to UV irradiation, mitomycin C, doxorubicin, cisplatin, sorafenib, and lapatinib. This sensitizing effect was not further changed as p53 expression had been simultaneously silenced. Following cell stress, NPM and BAX were induced and exported out of nucleoli and nucleus, respectively. BAX was translocated to cytoplasm in cells with relatively high NPM level, or accumulated in the mitochondria in cells with relatively low NPM level and undergoing apoptosis. Subcellular fractionation revealed that silencing of NPM expression greatly enhanced mitochondrial translocation and oligomerization of BAX in Huh7 and Mahlavu cells. In situ proximity ligation assays and reciprocal co-immunoprecipitation evidenced direct interaction between NPM and BAX in the cytoplasm. Silencing of BAX expression abolished the sensitization effect exerted by silencing of NPM in HCC cells. Clinically, upregulation of NPM was significantly associated with advanced tumor stage and poor prognosis. Conclusion: Via directly blockading BAX mitochondrial translocation and activation, NPM helps human HCC cells evade death induction independently of p53-mediated cell death. Silencing of NPM significantly sensitized HCC cells to anticancer therapies. NPM is a potential co-target in combination with other therapies for HCC particularly harboring inactivated p53. Our findings are of clinical significance, since NPM upregualtion and p53 mutations are usually found in advanced human cancers, including HCC. Citation Format: Sen-Yung Hsieh. A novel NPM-BAX pathway regulates death evasion and drug sensitivity in human hepatoma 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 1714. doi:10.1158/1538-7445.AM2013-1714
POTENT ANTISENSE OLIGONUCLEOTIDES TO APO(A) NORMALIZE PLASMA LP(A) LEVELS IN THE MAJORITY OF PEOPLE WITH ELEVATED LP(A): RESULTS OF ISIS-APO(A)RX PHASE 2 AND ISIS-APO(A)-LRX PHASE 1 TRIALS
Authors: Nick Viney, Santica Marcovina, Shuting Xia, Richard Geary, Joseph Witztum, Sotirios Tsimikas
Journal: Journal of the American College of Cardiology (2016)
Abstract 698: Overexpression of the aryl hydrocarbon receptor correlates with high tumor grade in human breast invasive carcinomas
Authors: Sakina E. Eltom, Petra Prins, Maria G. Olivares, Billy R. Ballard, Kimberly N. Johnson, Nara D. Granja-Ingram, Vincent K. Agboto, Tan Ding
Journal: Cancer Research (2012)

Abstract The aryl hydrocarbon receptor (AhR) is a ligand-activated basic helix-loop-helix transcription factor which binds environmental poly aromatic hydrocarbons (PAH) and mediates their carcinogenic effects. Recent reports, including data from our laboratory implicate AhR in breast cancer development and progression independent of the receptor occupancy by PAH. In this study we investigated the potential of AhR as a stage specific marker of breast cancer. We examined the expression of AhR by immunohistochemistry in tissue microarrays (TMA) containing 192 specimens of clinically defined three stages of invasive breast cancer: node-negative (NN), node-positive (NP) and metastatic (Met) carcinoma. The TMA were obtained from the National Cancer Institute Cooperative Breast Cancer Tissue Resource [NCI-CBCTR] and were stained for AhR using high affinity antibody. The AhR staining was then scored by three evaluators, including two pathologists who were blinded to the study. Statistical analysis showed a significant correlation between the AhR expression and the carcinoma case type (NN, NP or Met) (p-value of ANOVA is &amp;lt; 0.0003), and although there is a significant difference of AhR expression among carcinoma case type of white women (p&amp;lt; 0.0017) there is no significant difference for black women (p&amp;lt;0.0968). There is also a strong positive correlation between the receptor expression and the tumor grade (p &amp;lt;0.0001). While there is no correlation with the status of estrogen or progesterone receptors (p= 0.1643 and 0.1884, respectively), there is strong correlation of high AhR expression and invasive breast carcinoma in women over 50 years old (p&amp;lt;0.0043). In conclusion, our findings identify the AhR as a new predictive clinical marker for metastatic breast cancer and a unique target for the design of novel selective inhibitors for therapeutic intervention of metastatic breast cancer. More importantly, the AhR overexpression identifies a subset of patients who could benefit from therapy targeting this receptor. 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 698. doi:1538-7445.AM2012-698
Abstract 5019: Reprogramming the cancer epigenome by “metabolic transduction”
Authors: Jung S. Byun, Kevin Gardner
Journal: Cancer Research (2012)

Abstract This study focuses on the key concept of “metabolic transduction” as an important general mediator of cellular reprogramming in epithelial cancers. As a result of multiple studies on epithelial-to-mesenchymal transition (EMT) and mesenchymal-to-epithelial transition in diverse epithelial cancers, the role of developmental plasticity during epithelial differentiation has emerged as a new area of research. Recent data from our lab suggest that metabolites and intermediates in cellular metabolism can act as secondary messengers to dynamically change and globally reprogram epigenetic signatures during normal development, tissue repair, and cancer. We refer to this process as metabolic transduction. Central to this concept is the role played by the C-terminal binding proteins, CTBP1 and CTBP2. Dimeric combination of these factors act as metabolic sensors that function, in the presence of the high energy intermediate NADH, to target multiple classes of chromatin modifying factors, including histone deacetylase, histone methyl-transferases, histone demethylases, DNA methyl-transferases to specific locales throughout the genome. Therefore, CTBP has the potential to mediate widespread changes in the epigenetic landscape and influence broad programs of cellular behavior. Genome-wide profiling studies by ChIP-seq reveal that CTBP controls a network of genes linked to cellular events that influence cellular re-programing or “plasticity” including stem cell transcriptional programs, angiogenesis, and EMT. These studies combined with immuno-histochemical profiling of patient samples indicates that CTBP plays an important role in driving progression of more aggressive forms of breast cancer including Triple Negative Breast Cancer and the basal-like subtypes. Recent studies in our group suggest a role for CTBP in enabling plasticity of cellular fate in malignant cells. Breast cancer cell lines capable of spontaneous de-differentiation into side populations with tumor initiation cell characteristic, such as Sum149PT, are highly enriched in CTBP and are dominated by CTBP controlled pathways. This association has significance in diverse types of cancer, since other transformed cell lines capable of spontaneous de-differentiation into side population, including the endometrial carcinoma cell line HEC-1A, show similar enrichment and dependency on CTBP. These striking similarities suggest that CTBP may represent a driver of a tumor cell plasticity, implicating this tumor cell feature as a new hallmark of epithelial cancers. Therefore, strategies to target CTBP, and cellular reprogramming in general, may provide new opportunities for therapeutic intervention. 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 5019. doi:1538-7445.AM2012-5019
Factors affecting both peripheral blood progenitor cell mobilization and hematopoietic recovery following autologous blood progenitor cell transplantation in multiple myeloma patients: a monocentric study
Authors: G Marit, F Thiessard, C Faberes, P Cony-Makhoul, JM Boiron, P Bernard, A Pigneux, M Puntous, P Agape, G Vezon, A Broustet, D Girault, LR Salmi, J Reiffers
Journal: Leukemia (1998)
The need for DXA assessment of breast cancer patients following 5 years tamoxifen prior to starting an aromatase inhibitor.
Authors: L Brown, KJ Whannel, A McLennan, CR Wilson, JC Doughty
Journal: Cancer Research (2009)

Abstract Abstract #6141 Introduction: Aromatase inhibitors are increasingly being used in the adjuvant treatment of post-menopausal women with breast cancer. They are more effective than tamoxifen in terms of disease free survival and have a different side effect profile, all causing loss of bone mineral density. They can be introduced at different points in the adjuvant pathway. It has been postulated that if given in the extended setting, letrozole after 5 yrs tamoxifen, bone health may be less important. Tamoxifen is reported to increase bone mineral density so should make subsequent bone mineral density reduction with letrozole less significant. The aim of this study was to determine whether DXA scanning should be undertaken in women following 5 yrs of tamoxifen prior to starting letrozole.&amp;#x2028; Method: 166 women who had completed 5 years of tamoxifen underwent DXA with assessment of vertebral morphometry and risk factors associated with osteoporosis and fracture rate.&amp;#x2028; Results: Mean age was 63yrs (standard deviation [S.D] 10yrs); 154 women were post menopausal being at least 2 years after their last menstrual period; 12 women were unable to recall when they menopaused. Mean t-score and S.D was calculated at each site; spine -1.26(1.3); femoral neck -1.16(1.1) and total hip -0.91(1.1). Results were categorised by lowest t-score.&amp;#x2028; &amp;#x2028; Conclusion: We have demonstrated that of 166 women following completion of 5 yrs tamoxifen 26.5% have osteoporosis and 35.5% osteopenia. 28% required treatment with bisphosphonates. It cannot be assumed that Tamoxifen will cause a sufficient increase in BMD to render DXA scanning unnecessary. All patients should have DXA scanning following completion of 5 yrs tamoxifen prior to commencing letrozole. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 6141.
Intravital and Kidney Slice Imaging of Podocyte Membrane Dynamics
Authors: Sebastian Brähler, Haiyang Yu, Hani Suleiman, Gokul M. Krishnan, Brian T. Saunders, Jeffrey B. Kopp, Jeffrey H. Miner, Bernd H. Zinselmeyer, Andrey S. Shaw
Journal: Journal of the American Society of Nephrology (2016)

In glomerular disease, podocyte injury results in a dramatic change in cell morphology known as foot process effacement. Remodeling of the actin cytoskeleton through the activity of small GTPases was identified as a key mechanism in effacement, with increased membrane activity and motility in vitro . However, whether podocytes are stationary or actively moving cells in vivo remains debated. Using intravital and kidney slice two–photon imaging of the three-dimensional structure of mouse podocytes, we found that uninjured podocytes remained nonmotile and maintained a canopy-shaped structure over time. On expression of constitutively active Rac1, however, podocytes changed shape by retracting processes and clearly exhibited domains of increased membrane activity. Constitutive activation of Rac1 also led to podocyte detachment from the glomerular basement membrane, and we detected detached podocytes crawling on the surface of the tubular epithelium and occasionally, in contact with peritubular capillaries. Podocyte membrane activity also increased in the inflammatory environment of immune complex–mediated GN. Our results provide evidence that podocytes transition from a static to a dynamic state in vivo , shedding new light on mechanisms in foot process effacement.
AB0332 Echocardiographic Assessment of Ambulatory Rheumatoid Arthritis Patients with and without Periodontitis
Authors: J.P. Vinicki, F. Cintora, A. Saad, O. Fernandez, L. Nicolosi, S. Berensztein, G. Nasswetter
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Rheumatoid Arthritis (RA) is a chronic inflammatory disease that affects 1% of the world9s population. Patients with RA are at increased risk of cardiovascular disease (CVD) and they have lower survivals rates than the general population mainly due to an accelerated atherosclerosis caused by inflammatory mechanisms. Periodontitis (PO) is frequent in patients with RA and is also associated with systemic inflammation. The coexistence of both processes could potentiate the cardiovascular impact of RA. <h3>Objectives</h3> The purpose of this study was to evaluate systolic and diastolic cardiac function by echocardiography and tissue Doppler imaging in patients with RA with and without PO. <h3>Methods</h3> Patients with diagnosis of RA (ACR/EULAR, 2010) were included. Exclusion criteria were atrial fibrillation and known structural heart disease of any etiology. All patients underwent odontologic evaluation, 2D echocardiography, echo-Doppler and tissue Doppler imaging following recommendations of the American Society of Echocardiography. Patients were classified into 3 groups according to the presence of PO (G1: no PO, G2: mild PO, G3: moderate/severe PO). Categorical variables were compared with χ<sup>2</sup> test and continuous variables were compared with ANOVA. A p&lt;0.05 was considered statistically significant. <h3>Results</h3> Seventy-two patients with RA (mean age 55±13 years, 96% female) were included. Forty one patients were classified in G1, 16 in G2 and 15 in G3. There were no significant differences in age, prevalence of cardiovascular risk factors, anthropometric measures and time since diagnosis of RA between groups. G3 had a higher prevalence of male sex (G3: 20%, G1: 0% and G2: 0%; p=0,002). Table 1 shows the main results of echocardiographic evaluation. There were no significant differences between groups in structural, systolic or dyastolic parameters. <h3>Conclusions</h3> In this cohort of patients, periodontitis was not associated with structural or functional heart changes as assessed by comprehensive echocardiographic evaluation. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.6069
AB1290 Ultrasound evaluation correlates with disease activity in RA patients: Results of the SONAR-SCQM database:
Authors: P. Zufferey, L. Bruhlart, G. Tamborrini, A. Scherer, H.R. Ziswiler
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Ultrasound has been shown to be more sensitive than clinical examination for detecting synovitis and many studies have shown that it can be a reliable tool for monitoring RA patients. There are however few reports on its use in common practice, outside studies and or specialized centers. Since 2008, the Swiss Sonography in Arthritis and Rheumatism (SONAR) group has developed a reproducible semi-quantitative score for RA using OMERACT criteria for synovitis. The score includes B mode and Doppler mode. The score has been learned by 70 rheumatologists and since 2009 included as a routine evaluation tool in the Swiss SCQM RA cohort. <h3>Objectives</h3> To evaluate the correlation between the ultrasound scores and conventional outcome measures of disease activity (DAS28ESR or DAS28CRP) in the RA patients. <h3>Methods</h3> The SONAR score includes a semi-quantitative B mode and Doppler evaluation of metacarpo-phalangeal and proximal interphalangeal joints 2 to 5, wrist, elbows and knees (22 joints, grade: 0 to 3,t maximum of 66 points each). From January 2009 to January 2012, 508 patients included in the SCQM registry had at least one SONAR evaluation. Only the first available visit was analysed. Simultaneous DAS28 assessments were available in 337 patients for DAS28ESR, in 345 for DAS28CRP. Analysis comprised Pearson correlation between b mode and Doppler score compared to DAS28ESR and DAS28CRP values. We also analysed the SONAR scores within the classical categories of DAS activity: remission (&lt;2.6), low disease activity (&gt;2.6&lt;3.2), moderately active disease(&gt;3.2&lt;5), very active disease(&gt;5). <h3>Results</h3> There was a moderate significant linear correlation between the SONAR B mode score and clinically assessed disease activity: (Pearson coefficient r: 0.43 for DAS-ESR, r: 0.39 for DAS-CRP). The same was true for the SONAR Doppler score (Pearson r: 0.37 for DAS-ESR, r: 0.39 for DASCRP). Although, the mean SONAR scores (both b-mode and Doppler) differed significantly (p&lt;0.05) within categories of DAS, except for the low and moderate active disease groups, the individual scores were largely overlapping with some discrepancies (see table below). <h3>Conclusions</h3> The SONAR ultrasound score can be used in daily clinical practice by practicing rheumatologists and correlates with clinical measures of disease activity. However, on an individual level, many discrepancies and overlapping results exist, especially among patients with low or moderate active disease. The significance of these discrepancies, in particular the persistence of US synovitis in patients clinically in remission or low disease activity, needs to be further evaluated in a longitudinal study. <h3>Disclosure of Interest</h3> None Declared
Abstract P4-09-03: Comparative proteomic analysis identifies a 15-protein signature related to clinical outcome of triple negative breast cancer
Authors: Ning Qing Liu, Tommaso De Marchi, Christoph Stingl, Annemieke M Timmermans, Maxime P Look, René BH Braakman, Marcel Smid, Renée Foekens, Anita MAC Trapman, Theo M Luider, John WM Martens, John A Foekens, Arzu Umar
Journal: Cancer Research (2012)

Abstract Withdrawn by Author Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P4-09-03.
Abstract 2191: The Wnt/DVL signaling antagonist DACT2 is a pro-apoptotic tumor suppressor epigenetically silenced in multiple tumors and inhibits tumor cell proliferation and migration
Authors: Yichao Fan, Ying Ying, Lili Li, Anthony TC Chan, Qian Tao
Journal: Cancer Research (2011)

Abstract Wnt/DVL/β-catenin signaling pathway is aberrantly activated in a wide range of human cancers which frequently involves the disruption of its negative regulators, hence we would like to identify tumor suppressor as the antagonist to this signaling pathway. We identified a DACT (Dpr/Frodo) family member DACT2 as a downregulated gene in human tumors. Further epigenetic study revealed that, in contrast to its broad expression in normal tissues and cell lines, DACT2 is silenced or downregulated in multiple tumor cell lines including nasopharyngeal (NPC), esophageal (ESCC), gastric, colorectal (CRC), breast, lung, renal (RCC), hepatocellular (HCC), prostate and cervix carcinomas, due to its promoter methylation which could be reversed by pharmacological demethylation. DACT2 promoter methylation was also frequently detected in multiple primary tumors, suggesting that DACT2 is a potential tumor marker. DACT2 encodes a cytoplasm protein localized in endosome. Ectopic expression of DACT2 dramatically inhibited tumor cell colony formation in silenced tumor cell lines, mainly through inducing apoptosis. DACT2 interacts and downregulates Dishevelled (DVL) protein, thus protecting glycogen synthase kinase 3β (GSK-3β) from inactivation by WNT/DVL and allowing GSK-3β to form a complex with Axin and APC to promote the phosphorylation and proteasomal degradation of β-catenin. Overexpression of DACT2 disrupted β-catenin activation and accumulation in nucleus, thus preventing its binding to transcription factors of the Lef/Tcf family. This caused the downregulation of target oncogenes such as c-Myc, CCND1 and fibronectin and the inhibition of tumor cell proliferation and migration. We also observed that DACT2 could upregulate epithelial cell marker E-cadherin, and modulate Akt/GSK-3β/β-catenin signaling pathway, another pathway involved in tumor cell epithelial mesenchymal transition. Our data demonstrate that DACT2 is a functional tumor suppressor epigenetically silenced in multiple tumors which acts as a negative regulator of the Wnt/DVL/β-Catenin pathway, and could be a promising biomarker for human tumors. 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 2191. doi:10.1158/1538-7445.AM2011-2191
Treatment of Thoracic Aortic Aneurysms by the Pack Method of Intrasaccular Wiring
Authors: Robert R. Linton, Irad B. Hardy
Journal: New England Journal of Medicine (1952)

ANEURYSM of the thoracic aorta is a disease of great antiquity. It was described as early as the sixth century by Aëtius.1 Ambroïse Paré, the great sixteenth-century French surgeon, was the first to suggest the relation of aneurysm and syphilis, according to Butler.1 During the nineteenth century and the early part of the twentieth, aneurysms were reputed to occur more frequently in this location than elsewhere in the body. In 1847 Crisp,2 in a series of 530 cases, found 175 of the thoracic aorta compared to 59 of the abdominal aorta. Klotz,3 in 1926, reviewing 1000 cases, reported 610 and . . .
Soft signs and neuropsychological performance in schizophrenia
Authors: L A Flashman, M Flaum, S Gupta, N C Andreasen
Journal: American Journal of Psychiatry (1996)

Both neuropsychological impairment and neurological soft signs have been documented in at least a subset of patients with schizophrenia. The purpose of the present study was to examine the relationship between soft signs and neuropsychological performance in patients with schizophrenia in order to address the issue of whether soft signs are related to global or more selective cognitive impairment.Patients with a DSM-III-R diagnosis of schizophrenia (N=176) were given a standardized neuropsychological battery and underwent a neurological examination. The study group was dichotomized on the basis of presence or absence of neurological soft signs.Patients with neurological soft signs (N=68) demonstrated significantly poorer performance on neuropsychological tasks that assessed timed motor speed and motor coordination (e.g., finger tapping, the Purdue Pegboard task, and part B of the Trail Making Test). These findings continued to be significant even after lifetime medication exposure, extrapyramidal symptoms, and abnormal involuntary movements were used as covariates.These findings support the notion that soft signs are a manifestation of a localizable behavioral deficit of the systems that are involved in motor speed, coordination, and sequencing and are not indicative of global cognitive impairment. The specific deficit in motor abilities is consistent with the types of neurological soft signs that are most frequently reported and suggests involvement of frontal/subcortical circuitry in schizophrenia.