tbuckley/cabot-search huggingface dataset:
Abstract 1186: Differences in the levels, localization and DNA binding of p53 in breast cancer cell lines
Authors: Debolina Ray, Keith R. Murphy, Susannah Gal
Journal: Cancer Research (2012)

Abstract Mutations in the p53 tumor suppressor affect protein accumulation, localization and DNA binding. We undertook to determine these properties of p53 in breast cancer cells and to see how those attributes change following oxidative stress. We analyzed the p53 in 8 different breast cancer cell lines, with either wild-type or mutant p53 protein. By ELISA and western blots, we found that the levels of the p53 protein were generally low for cells carrying wild-type protein and high in cells having a mutation in the TP53 gene. This was contrasted to the case in the HCC2157 cell line which has wild-type p53 but accumulates the protein to high levels. Using biotinylated DNA and streptavidin magnetic beads, we found that wild-type p53 protein from MCF-7 and ZR-75-1 cells binds with different affinity to 12 gene sequences covering several pathways regulated by p53. Treatment of MCF-7 cells with H2O2 caused an increase in this binding affinity. The p53 from the HCC2157 cells and all of the mutant p53 proteins had minimal to weak binding to these sequences even after treatment with H2O2. We also analyzed the phosphorylation of serine 15 on p53 in 4 of the cell lines. The p53 protein from the HCC2157 cells and two other cell lines showed phosphorylated protein at this site, but we found no correlation between that modification and the levels, localization, or binding affinity of the protein. From this and other work, it appears that the mutation status of the TP53 gene alone can not predict the activity of this tumor suppressor since cell lines with the same genetic information do not show the same properties of this protein. We argue that the analysis of DNA binding or transcription activity must be done in order to correlate the functionality of p53 with clinical outcome in tumors. 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 1186. doi:1538-7445.AM2012-1186
Hepatobiliary Scintigraphy in an Immunosuppressed Patient with Hepatocellular Dysfunction and Acute Cholecystitis: Diagnostic Dilemmas Posed by Delayed Gallbladder Visualization
Authors: ZAKARIA ASSI, NICOLAAS I. BOHNEN, BRAHM SHAPIRO
Journal: Clinical Nuclear Medicine (1998)

A case of acute cholecystitis in an immunosuppressed patient with hepatocellular dysfunction is reported. The diagnostic dilemmas posed by the lack of specific sonographic findings, the possibility of acute gallbladder disease without early cystic duct obstruction, and the absence of clear guidelines for the interpretation of delayed appearance of the gallbladder on hepatobiliary scintigraphy in this subgroup of patients are discussed.
Clinical Impact of Differential Renal Function To Indicate and Assess Pyeloplasty and the Significance of Coexisting Vesicoureteral Reflux
Authors: TOBIAS SCHUSTER, MAXIMILIAN STEHR, BERND ROMÜLLER, HANS GEORGE DIETZ, KLAUS HAHN
Journal: Clinical Nuclear Medicine (2001)

In patients with ureteropelvic junction obstruction (JPJO) who are conservatively treated, 5% to 10% of them show a deterioration of renal function without recovery after delayed pyeloplasty. Should surgery be indicated based on observed deterioration of differential renal function (DRF)? Can we expect improvement of the DRF after pyeloplasty? What other influencing parameters may affect DRF?In this study, the authors examined 85 ureterorenal junctions that had undergone the Anderson-Hynes technique for surgical correction of UPJO. Based on the values obtained from the preoperative DRF (Tc-99m mercaptoacetyltriglycine), the cases were separated into three categories: group I had poor DRF (less than 11% of total renal function [TRF]), group II had moderate DRF (11% to 33% of TRF), and group III had adequate DRF (more than 33% of TRF). Twelve months after surgery, renal function was reassessed. The results were correlated with age at surgery, symptoms, coexisting vesicoureteral reflux, and drainage.Seven ureterorenal junctions (8%) comprised group I, 15 (18%) comprised group II, and 63 (74%) comprised group III. After UPJO repair, 13% showed marked improvement in DRF, 86% remained stable, and 1% exhibited diminished function. In 50% of the renal cases with preoperative DRF less than 33%, postoperative improvement was seen. In follow-up renal scans, 30 cases (35%) revealed nonobstructive drainage, whereas the remaining 53 junctions (62%) showed moderate delayed drainage. Both the moderate delayed group (57%) and the nonobstructive group (50%) showed similar DRF improvement. Sixty-six percent of the patients with impaired DRF improved after pyeloplasty performed within the first 3 months of life, compared with 42.8% of patients in whom surgery was performed after 5 years of age. Vesicoureteral reflux was evident in 27.2% of the patients with preoperative impaired DRF compared with 11% with normal DRF. Forty-five percent of the patients with impaired DRF and no improvement after surgery had coexisting vesicoureteral reflux, compared with 9% of those with postoperative improvement.Sustained renal impairment after pyeloplasty is likely as a result of preexisting renal dysplasia with vesicoureteral reflux. Moderate delayed drainage after surgery does not affect DRF. Surgery for UPJO should be indicated independent of a DRF follow-up (except very low DRF) or the age at the time of diagnosis.
AB0297 Does Delay of Therapy Affect Outcomes of Early RA in A T2T Clinic?: Table 1
Authors: T. Sokka-Isler, H. Kautiainen, T. Rannio, J. Asikainen, P. Hannonen
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Very early referral/start of therapy within 3-4 months vs. delayed referral has been shown beneficial for short- and long-term outcomes in rheumatoid arthritis (RA). However, treatment strategy in these studies was not a stringent T2T approach. In FIN-RACo study, 2-year remission rates were 11% in monotherapy patients who had &gt;4month-delay and 35% in patients who started therapy without delay within 4months after symptoms, while 42% of patients who received triple combination were in remission, regardless of delay of therapy indicating that early intensive therapy may overcome a delay. <h3>Objectives</h3> To study whether delay of therapy affects outcomes of RA in a real life setting in a clinic with a T2T approach. <h3>Methods</h3> A clinical database with data of all RA cases in a district of 275.000 population was analyzed for patients with a new diagnosis of RA in 1993-2013. Database includes variables for demographics, clinical course, outcomes, medications and the date of first symptoms of RA, a question which was asked from the patient at the first visit and recorded in the database. Duration of symptoms (delay) at initiation of therapy was categorized as 0-3mo, 4-6mo, 7-12mo, 13-24mo, and &gt;2yr. Outcome variables and medication data were available in 60-68% of patients at a mean of 7.3 years after diagnosis. <h3>Results</h3> In 1993-2013, 2374 patients (mean age 56yr, 67%F, 59%RF/CCP+) were diagnosed and treated with a median duration of symptoms of 5.5mo ranging from 4.5mo in 2005 to 7.4 in 2003 with no increasing/decreasing trend of delay over years. Existing musculoskeletal disease and younger age were associated with longer delay, adjusted for sero+/-, gender, and year of diagnosis. Overall, 32%, 24%, 24%, 10%, and 10% of patients had a delay of 0-3mo, 4-6mo, 7-12mo, 13-24mo, and &gt;2yr, respectively. No significant differences in outcomes and treatments were observed between the delay groups after a mean follow-up of 7 years (Table 1). <h3>Conclusions</h3> Delay of treatment start may have minor influence on outcomes in a T2T clinic. <h3>References</h3> Lard et al. AM J Med 2001. Gremese at al. ARD 2013. Ehrmann Feldman et al. Rheumatology 2013. Möttönen et al. A&amp;R 2002 <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.2245
A2.26 Serum IL-7 as diagnostic biomarker for rheumatoid arthritis, validation with Eular-2010 diagnostic criteria
Authors: AN Burska, J Neilan, RE Chisman, R West, P Emery, F Ponchel
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background and objectives</h3> Despite the well-established value of currently used diagnostic criteria for RA there is a constant demand for novel biomarkers to further improve early diagnosis notably in ACPA-negative patients. Inteleukin7 (IL-7) has been reported as a candidate diagnostic biomarker based on ACR-1987 criteria for RA, within 6 months of symptom development.<sup>1</sup> The aim of the present study was to validate these results using EULAR-2010 criteria. <h3>Materials and methods</h3> 255 patients attending early arthritis clinic were recruited. Demographic (age, gender, symptom duration) and clinical data (joint counts swollen and tender (SJC, TJC), CRP, DAS28, autoantibodies (RF and ACPA), SE) were collected. A commercial ELISA (R&amp;D Systems, Abingdon, UK) was used to measure IL-7. Univariate and regression analysis were used to model outcome. <h3>Results</h3> At follow-up over 24 months, 118 patients had a confirmed diagnosis of RA (EULAR-2010) while 137 were classified as non-RA (persistent UA, other diagnostic or non-inflammatory). The RA diagnosis was associated with ACPA, RF and SE positivity (p &lt; 0.001, univariate). RA patients had significantly higher SJC, TJC, DAS28 (all p &lt; 0.001) and CRP (p = 0.024). IL-7 tended to be lower in RA compared to non-RA (p = 0.100). To model for covariance, we used a regression analysis including IL7, ACPA (accounting for RF and SE as strongly associated), and SJC, TJC, CRP (as component of disease activity) including 227 patients with complete data set. IL-7 was the third best predictive marker (p = 0.035) following ACPA (p &lt; 0.001) and SJC (p = 0.007). A second model was developed investigating ACPA-negative patients only (n = 147, complete data). IL7 was the second best predictive marker (p = 0.075) behind SJC (p = 0.013). <h3>Conclusions</h3> This study validates previous results using the EULAR-2010 criteria for diagnosing RA (in UK population of patients), however the predictability associated with lower IL-7 is less significant than in the initial study using ACR-1987 criteria (in French cohort). IL-7 remains a potential biomarker for ACPA-negative RA although further validation with larger number of ACPA-negative RA is needed. Further replication studies are required to translate these results into clinical applicability. <h3>Reference</h3> Goëb VP, Aegerter R, Parmar P,&nbsp;<i>et al</i>. Progression to rheumatoid arthritis in early inflammatory arthritis is associated with low IL-7 serum levels. Ann Rheum Dis. 2013;72:1032–6
Randomized, Double-Blind Six-Month Trial of Prednisone in Duchenne's Muscular Dystrophy
Authors: J.R. Mendell, R.T. Moxley, R.C. Griggs, M.H. Brooke, G.M. Fenichel, J.P. Miller, W. King, L. Signore, S. Pandya, J. Florence, J. Schierbecker, J. Robison, K. Kaiser, S. Mandel, C. Arfken, B. Gilder
Journal: New England Journal of Medicine (1989)

We performed a randomized, double-blind, controlled six-month trial of prednisone in 103 boys with Duchenne's muscular dystrophy (age, 5 to 15 years). The patients were assigned to one of three regimens: prednisone, 0.75 mg per kilogram of body weight per day (n = 33); prednisone, 1.5 mg per kilogram per day (n = 34); or placebo (n = 36). The groups were initially comparable in all measures of muscle function. Both prednisone groups had significant improvement of similar degree in the summary scores of muscle strength and function. Improvement began as early as one month and peaked by three months. At six months the high-dose prednisone group, as compared with the placebo group, had improvement in the time needed to rise from a supine to a standing position (3.4 vs. 6.2 seconds), to walk 9 m (7.0 vs. 9.7 seconds), and to climb four stairs (4.0 vs. 7.1 seconds), in lifting a weight (2.1 vs. 1.2 kg), and in forced vital capacity (1.7 vs. 1.5 liters) (P<0.001 for all comparisons). There was an increase in urinary creatinine excretion (261 vs. 190 mg per 24 hours), which suggested an increase in total muscle mass. However, the prednisone-treated patients who had required long-leg braces (n = 5) or wheelchairs (n = 11) continued to require them. The most frequent side effects were weight gain, cushingoid appearance, and excessive hair growth. We conclude from this six-month study that prednisone improves the strength and function of patients with Duchenne's muscular dystrophy. However, further research is required to identify the mechanisms responsible for these improvements and to determine whether prolonged treatment with corticosteroids may be warranted despite their side effects. (N Engl J Med 1989; 320:1592–7.)
Abstract 2145: Identification of genomic alterations and integrated gene expression profiles for MSS colon tumors
Authors: Lenora W.M Loo, Maarit Tiirikainen, Iona Cheng, Gordon Okimoto, Annette Lum-Jones, Ann Seifried, Steven Gallinger, Steven N. Thibodeau, Graham Casey, Loic Le Marchand
Journal: Cancer Research (2010)

Abstract Colon cancer is the result of a multi-step process involving the accumulation of genetic and epigenetic alterations leading to the transformation of normal colon epithelium to adenocarcinoma. Identification of characteristic genetic alterations is of critical importance to increase our understanding of the transformation process. We focused our analysis on the most common molecular sub-type of colon cancers, microsatellite stable (MSS) and CpG island methylator phenotype (CIMP)-negative, to identify characteristic copy number alteration (CNA) events and associated gene expression profiles using high-resolution genome-wide microarrays. DNA and RNA were extracted from 41 fresh-frozen paired colon tumors and adjacent normal tissue collected by the Colon Cancer Family Registry. Genomic profiles, such as CNAs and loss of heterozygosity (LOH), were identified with the Affymetrix Genome-Wide Human SNP 6.0 array for both tumor and adjacent normal tissue. Gene expression profiles of tumors and adjacent normal tissue were identified with the Affymetrix GeneChip Human Exon 1.0 ST array. Partek Genomics Suite software was used for analysis and data integration. We identified recurrent (&amp;gt;25%) CNAs in several chromosomal regions: gain in 1q, 7p, 7q, 8q, 13q, 20p, 20q, Xp, Xq and loss in 5q, 8p, 14q, 16p, 17p, 18p, and 18q. In addition, based on the allele information from the SNP arrays, we found a subset of these recurrent CNAs were associated with LOH. Preliminary results from the integration of CNA and gene expression data in tumors indicate that a subset of these recurrent CNAs is associated with the disruption of gene expression. For example, we observed recurrent copy number gain in 8q24.21, the genomic region containing the c-MYC gene, and associated up-regulation of c-MYC gene expression in tumors compared to adjacent normal tissue. In another example, recurrent copy number loss at 5q22.2 was associated with down-regulation of APC gene expression; loss of function of this tumor suppressor is associated with both hereditary and sporadic colon cancer. This genome-wide characterization of both genomic alterations and gene expression may help identify key genes and pathways that are disrupted in this common molecular subtype of colon cancer. We will present detailed results from this integrated and comprehensive genetic profiling of MSS and CIMP-negative colon cancers. 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 2145.
AB0386 Sjögren’s syndrome associated with mpo-anca-positive polyangiitis.
Authors: A. Mersni, A. Hamzaoui, T. Ben Salem, H. Tounsi, I. Ben Ghorbel, M. Lamloum, M. Smiti, M. H. Houman
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Sjögren's syndrome (SS) is a chronic autoimmune disease that is commonly manifested by immune attack on the exocrine glands with resultant dry eyes and dry mouth. Sjögren's syndrome patients also have disease in other organs. <h3>Objectives</h3> To study the cases of SS associated with MPO-ANCA-positive polyangiitis. <h3>Results</h3> We report 4 cases (were female) with Sjögren syndrome developed microscopic polyangiitis. The accurate diagnosis of SS was established based on objective signs and symptoms of ocular and oral dryness and characteristic appearance of a biopsy sample from a minor salivary gland, and presence of anti-SS-A autoantibody. The patient also tested positive for myeloperoxidase-antineutrophil cytoplasmic antibodies (MPO-ANCA), with changes in the MPO-ANCA titer that paralleled changes in the symptoms. Histologic finding of skin biopsy of purpuric lesion was typical for leukocytoclastic vasculitis. Renal biopsy was performed for nephrotic range proteinuria. The pathologic finding of renal biopsy was necrotizing crescentic membranous glomerulonephritis. The patients were treated with oral glucocorticoids in combination with cyclophosphamide and with local symptomatic therapy for ocular and oral dryness. Renal function stabilized after 2 months, and tests for anti-myeloperoxidase reverted to negative. <h3>Conclusions</h3> SS is one of the most common autoimmune disorders and vasculitis is one of the most characteristic extraglandular manifestations, but wide spectrum of cutaneous involvement in SS has been little studied. <h3>Disclosure of Interest</h3> None Declared
Abstract 3334: Antiangiogenic activity of honokiol through inhibition of vascular vessel formation in the mouse embryonic stem cell-derived endothelial cells
Authors: Gi Dae Kim, Song Yi Bae, Yuna Pyee, Yoonho Shin, Min Ai Lee, Jayoung Song, Hwa Jin Chung, Hyen Joo Park, Sang Kook Lee
Journal: Cancer Research (2012)

Abstract Embryonic stem (ES) cells, which are characterized by pluripotency and self-renewal, have recently been highlighted in several aspects of drug discovery. In particular, the potential of ES cells to differentiate into specific-cell types make them an extremely useful tool in the evaluation of the biological activity of test compounds. In the present study, we employed mouse embryonic stem (mES) cell-derived embryoid bodies (EBs) to evaluate the antiangiogenic activity of natural compounds. Honokiol, a major neolignan derived from the bark of Magnolia obovata Thunberg (Magnoliaceae), was capable of inhibiting differentiation and vascular vessel formation in mES cell models. EBs were formed using hanging drop cultures. The induction of vascular formation was carried out on gelatin-coated plates in EGM-2 medium. Cell proliferation was measured by MTT assay. RT-PCR, immunocytochemistry, and Western blotting were used to measure differentiation of EBs into endothelial cells and vessel formation. The growth inhibition of honokiol in EB-derived endothelial cells was found that honokiol is more sensitive in the differentiated cells (on day 8) compared to the undifferentiated EB-derived endothelial cells (on day 1) with the IC50 values of 6.0 and 17.8 μM, respectively. Honokiol also dramatically decreased the expressions of an endothelial biomarker PECAM in the differentiated EB-derived endothelial cells (on day 11). Honokiol also suppressed the activation of p38 MAPK, Akt, ERK1/2 and SAPK/JNK in EB-derived endothelial cells. The antiangiogenic activity of honokiol is associated with the suppression of PECAM and the MAPK pathway in EB-derived endothelial cells. 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 3334. doi:1538-7445.AM2012-3334
Determinism and free will: review of the literature
Authors: F W Furlong
Journal: American Journal of Psychiatry (1981)

During the past century various theories of mental functioning that rest on a deterministic view of man have gained dominance. However, a review of psychodynamic writing shows that there has remained a need for some concept of autonomy and inner direction, as represented by the concepts of ego autonomy and behavioral self-control. In fact, some studies of mental health and psychotherapy can be interpreted as supporting the existential view that the experience of "freedom" and "choice" is a genuine phenomenon. Although concepts of behavioral self-control may reconcile these contradictions, the author concludes that no theories of mental functioning have entirely dealt with the paradoxes of autonomy, inner direction, and choice.
Abstract PR2: A genetic screen for novel determinants of anoikis resistance identifies PVRL4
Authors: Natalva N. Pavlova, Stephen J. Elledge
Journal: Cancer Research (2011)

Abstract Tumor cells develop resistance to detachment-induced cell death, known as anoikis, and rely on it for survival throughout the course of disease progression. Through a gain-of-function genetic screen for novel determinants of anoikis resistance, we found that PVRL4 (poliovirus receptor-like 4) promotes anchorage-independent colony formation in HMECs (human mammary epithelial cells). PVRL4 belongs to a family of transmembrane proteins involved in early stages of adherens junction formation. PVRL4 is expressed in focally amplified in breast cancer and positively correlates with spread of cancer into lymph nodes and poor survival prognosis. PVRL4 promoted cell aggregation of HMECs, and induction of cell aggregation was sufficient to promote anchorage-independent colony formation. Cell aggregation and transformation induced by PVRL4 were abrogated in presence of a monoclonal antibody targeting its extracellular region. Furthermore, stable depletion of PVRL4 in breast cancer cells inhibited spontaneous cell aggregation and anchorage-independent growth. Taken together, our findings demonstrate the key role of PVRL4 in cellular transformation and suggest that it functions via promoting cell aggregation. Cancer cells are known to exhibit increased cell aggregation; moreover, increased cell aggregation correlates with metastatic potential. Multicellular clusters of cancer cells are present among circulating tumor cells (CTCs) blood from cancer patients and as well as in mouse cancer models. Promotion of survival in the absence of attachment via inducing cell aggregation may therefore provide a unique advantage for CTC survival in the bloodstream and spread into distant organs. Finally, inhibition of PVRL4-induced aggregation and anchorage-independence by monoclonal antibodies demonstrates a potential new therapeutic strategy against breast cancer. This abstract is also presented as Poster B5. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the Second AACR International Conference on Frontiers in Basic Cancer Research; 2011 Sep 14-18; San Francisco, CA. Philadelphia (PA): AACR; Cancer Res 2011;71(18 Suppl):Abstract nr PR2.