tbuckley/cabot-search huggingface dataset:
Abstract LB-101: Y-box binding protein-1 (YB-1) inhibition triggers differentiation of normal and cancer stem cells from the brain
Authors: Abbas Fotovati, Sam Abu-Ali, Pei-Shan Wang, Loic Deleyrolle, Cathy Lee, Joanna Tricott, James Chen, Sonia Franciosi, Yas Nakamura, Yasuo Sugita, Takeshi Uchiumi, Michihiko Kuwano, Blair R. Leavitt, Sheila Singh, Alexa Jury, Chris Jones, Hiroaki Wakimoto, Brent A. Reynolds, Catherine J. Pallen, Sandra E. Dunn
Journal: Cancer Research (2011)

Abstract The Y-box-binding protein-1 (YB-1) is up-regulated in many human malignancies including glioblastoma (GBM). It is also essential for normal brain development, suggesting that YB-1 is part of a neural stem cell (NSC) network. Here we show that YB-1 was highly expressed in the subventricular zone (SVZ) of mouse fetal brain tissues but not in terminally differentiated primary astrocytes. Conversely, YB-1 knock-out mice had reduced Sox-2, nestin and musashi expression in the SVZ. While primary murine neurospheres were rich in YB-1, its expression was lost during glial differentiation. Likewise, YB-1, Sox-2, mushashi, Bmi-1 and nestin are coordinately expressed in SF188 cells and 9/9 GBM patient-derived primary CSCs. Silencing YB-1 with small interfering RNA attenuated the expression of these NSC markers, reduced neurosphere growth and triggered differentiation via coordinate loss of GSK3-β. Further, differentiation of CSCs with 1% serum or bone morphogenetic protein-4 (BMP-4) suppressed YB-1 protein expression. Likewise, YB-1 expression was lost during differentiation of normal human NSCs. Consistent with these observations, YB-1 was preferentially expressed in highly undifferentiated primary gliomas based on the analysis of WHO grade 1-IV tumors (n=49 cases). YB-1 was also co-expressed with Bmi-1 (Spearmans 0.80, p&amp;gt;0.001) and Sox-2 (Spearmans 0.66, p&amp;gt;0.001) based on the analysis of 282 cases of high-grade gliomas. These CSC markers were also highly expressed in 10/15 (67%) of GBM patients that subsequently relapsed. In conclusion, YB-1 is a key feature of stem cells where it functions to suppress differentiation. 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 LB-101. doi:10.1158/1538-7445.AM2011-LB-101
Responsible Exchange of Ideas and Libel Law
Authors: RAYMOND S. FERSKO
Journal: JNCI Journal of the National Cancer Institute (1992)

Journal Article Responsible Exchange of Ideas and Libel Law Get access RAYMOND S. FERSKO RAYMOND S. FERSKO Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 84, Issue 6, 18 March 1992, Page 450, https://doi.org/10.1093/jnci/84.6.450 Published: 18 March 1992
P587MiR-29a controls cardiac stem cells differentiation through Dnmt3a-mediated extinction of Wnt/beta-catenin
Authors: A De Pauw, B Sekkali, A Loriot, C De Smet, D Catalucci, D Hilfiker-Kleiner, J-L Balligand
Journal: Cardiovascular Research (2014)

Epigenetic programming within the cardiac stem cell (CSC) niche controls CSC specification and differentiation, but the identity of putative mediators is poorly characterized. To dissect these mechanisms, we used primary and clonally expanded Sca-1+/c-kit+ CSC from murine adult hearts and stimulated cardiomyocyte differentiation upon culture in a differentiation medium (DIFF) containing 5'-Azacytidine and transforming growth factor β1 or co-cultured with rat cardiomyocytes. With this model, we previously showed that inducible deletion of β-catenin enhanced CSC differentiation in vitro and in vivo. Accordingly, we detected a constitutive activity of Wnt/b-catenin pathway in undifferentiated CSC and a downregulation of Wnt target genes (in % of ctl: Axin2: 36±4%; Snai2: 46±7%; n=3; p<0.01) in CSC treated with DIFF medium, associated with an upregulation of Wnt antagonist, Wif-1 (310±57%; n=3, p<0.05). Like several Wnt/b-catenin repressor genes, Wif-1 gene expression is DNA methylation sensitive and susceptible to be regulated by the de novo DNA methyltransferases Dnmt3. Indeed, Dnmt3a was downregulated in CSC treated with DIFF, while siRNA targeting Dnmt3a upregulated Wif-1 expression in non-differentiated cells (425±254%; n=4, p<0.05) and promoted CSC cardiac differentiation in co-culture assay (assessed by quantitative expression of cTnT; 162±7% vs. siRNA-scramble; n=7, p<0.001). In parallel, we found an early upregulation of miR-29a (444±43%; n=3, p<0.01), a well-known regulator of Dnmt3a, in DIFF-treated CSC. Indeed, early treatment of CSC with miR-29a mimic decreased Dnmt3a protein level and increased Wif-1 expression (839±257%; n=4, p<0.05). Reciprocally, CSC treatment with anti-miR-29a (LNA-miR-29a; vs scramble ctl) upregulated Dnmt3a and downregulated Wif-1 expression (51±9%; n=7, p<0.01). Importantly, this treatment also significantly decreased CSC differentiation in co-culture assay (63±4% vs. LNA-scramble; n=11, p<0.001). Altogether, this suggests that upregulation of miR-29a promotes differentiation (and blockade of miR-29a inhibits differentiation) through Dnmt3a-dependent regulation of the Wnt inhibitor, Wif-1. In support of this, co-treatment with anti-miR-29a and siRNA-Dnmt3a abrogates the above effect both on Wif-1 expression and CSC differentiation (compared to treatment with respective scramble, n=7). We conclude that differentiation of CSC involves the epigenetic regulation of canonical Wnt/β-catenin activity through miR-29a and Dnmt3a-dependent control of expression of the endogenous inhibitor, Wif-1, possibly amenable to therapeutic modulation for cardiac repair.
THU0310 Predictors of Therapeutic Success of Steroids Injection in the Carpal Tunnel Syndrome: A Retrospective Multivariate Analysis of A Multicenter Cohort
Authors: C.A. Guillen Astete, M. Luque Alarcon, A. Boteanu, A. Zea
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Treatment of moderate to severe carpal tunnel syndrome includes the possibility of local steroid injections, however the treatment success rate and its duration are very variable. There is no study designed to predict if a local steroid injection will be success or not. Sometimes local steroids injections delays surgical procedures without solving patient symtoms. A marker capable to predict success of failure should be useful in terms of chosing best therapy for these patients. <h3>Objectives</h3> The purpose of this study was to determine the weight of different factors as predictors of the therapeutic success of steroid joint injections. <h3>Methods</h3> We conducted a retrospective study with a cohort of 166 patients diagnosed with moderate or severe carpal tunnel syndrome according to electrophysiological criteria and who had undergone carpal ultrasound between 2010 and 2013. A multivariate analysis, using as the variable response a reduction in the score at the Boston Carpal Tunnel Syndrome Questionnaire three months after the steroid infiltration was performed. <h3>Results</h3> The presence of positive power- Doppler signal in the carpal tunnel showed a high correlation with the improvement at the Boston Carpal Tunnel Syndrome Questionnaire (Pearson r -0.7079, p=0.0001) in the bivariate analysis, and a ratio of 49.8% in the multivariate analysis (Heat coeff -0.4777 [95% CI -1.4775 to -0.5612], p&lt;0.0001). Other relevant variables were: duration of symptoms (Heat coeff 0.0071 [95% CI 0.0025 to 0.0117], p=0.0027), the cross-sectional area of the median nerve within the carpal tunnel (Heat coeff 0.0223 [95% CI 0.0023 to 0.0424], p=0.0293) and age (0.0029 Heat coeff [CI -0.0005 to 0.0064], p=0.0979). <h3>Conclusions</h3> Our results suggest that the therapeutic success of infiltration is mainly associated with the finding of power- Doppler signal. According to our analysis we believe it is reasonable to recommend steroids joint injections in patients with this finding and to consider the risk/benefit in patients without this sonographic predictor. <h3>Acknowledgements</h3> To Dr. Domingo Ly Pen for his contribution to this study. <h3>Disclosure of Interest</h3> : None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.5556
Acute Pancreatic Lesions in Patients Treated with ACTH and Adrenal Corticoids
Authors: Frank A. Carone, Averill A. Liebow
Journal: New England Journal of Medicine (1957)

CASUAL observations of post-mortem material have suggested an increased frequency of necrosis and other lesions in the pancreas and adjacent tissues in patients receiving certain adrenocortical steroids or ACTH. The present study is an attempt at a more accurate quantitative evaluation of these findings.Our interest was stimulated by reports from two laboratories of pancreatic lesions induced by cortisone in rabbits. Stumpf and his co-workers1 found changes in pancreatic acini in 44 of 53 cortisone-treated animals and peripancreatic fat necrosis in 13 of these animals. Bencosme and Lazarus2 described similar lesions in their series of rabbits treated with this steroid. . . .
AB0597 Comparative analysis of safety data of four treatment regimens in early rheumatoid arthritis patients
Authors: E. Fedorenko, G. Lukina, Y. Sigidin, D. Karateev, E. Luchikhina, E. Nasonov
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Objectives</h3> To compare safety data in patients (pts) with early (&lt;2 years duration) RA who were randomly assigned to receive 4 different regimens of DMARDs treatment. <h3>Methods</h3> One hundred forty-one pts with RA of less than 2 years duration (122 women, mean age 51 years, mean disease duration 24 weeks, mean DAS 28 5,9; 64% RF-positive,59% ACCP-positive) were randomly allocated to receive one of the following treatment regimens: methotrexate (MTX, up to 20 mg/week, 35 pts); MTX plus prednisolone (P) 10 mg daily (MTX-P, 34 pts); MTX-P plus methylprednisolone (MP) 1000 mg intravenously on the first day of treatment (MTX-P-MP, 35 pts); leflunomide 20 mg daily (LEF, 37 pts). Duration of treatment was one year. Control points were 3, 6 and 12 months from the initiation of therapy. Safety data was assessed at the main control points. <h3>Results</h3> At baseline all groups were comparable in their demographic, clinical and radiographic characteristics. One hundred twenty-seven pts completed the study. Side effects were registered in the same number of patients in each group (9 patients; 24,3%&gt;26%). Therapy had to be stopped in six patients due to side effects: MTX - 1(depigmentation of the skin), MTX-P - none, MTX-P-MP - 1 (stomatitis) and LEF - 4 (dermatitis-2; pancytopenia with platelet count 43 ×10<sup>9</sup>/L, erythrocyte 2,9×10<sup>12</sup>/L, WBC 2×10<sup>9</sup>/L-1; angioedema, periorbital edema and dermatitis with itching-1). Other side effects were mild: MTX - 8 pts (dyspepsia-1, elevation of transaminases-6, hair loss-1), MTX-P - 9 pts (Cushing's syndrome - 1, hair loss - 1, anemia - 1, elevation of transaminases - 4, arterial hypertension - 2), MTX-P-MP - 8 pts (hair loss-1,dermatitis-1, elevation of transaminases-5, Cushing's syndrome - 1) and LEF - 5 pts (elevation of transaminases-5). <h3>Conclusions</h3> Safety profile was the same in all groups. In most cases side effects were moderate or minimal. The most serious side effects, leading to the discontinuation of the therapy, were registered in LEF group. There was no withdrawal of treatment in MTX-P group. <h3>Disclosure of Interest</h3> None Declared
PTU-055 A Comparison Of Radiological And Endoscopic Oesophageal Stent Placement In Malignancy
Authors: T Chapman, H Tyrell, H Al-Hassani, A Colcer, A Bruce, N Rajoriya, D Warakaulle, D Gorard, R Sekhar
Journal: Gut (2014)

<h3>Introduction</h3> Self expanding metallic stent (SEMS) placement effectively palliates malignant dysphagia, most commonly due to oesophageal cancer. Typically stents are placed under fluoroscopic guidance, but some centres use direct vision endoscopy as an alternative.<sup>1</sup> There are however little data comparing the two techniques. At our 2-hospital institution, all patients presenting to Stoke Mandeville Hospital undergo radiologically guided stent placement, while patients at Wycombe Hospital undergo endoscopic placement without fluoroscopy. We describe our experience over a three year period. <h3>Methods</h3> A retrospective observational study of all patients who underwent SEMS placement at our two hospitals over a three year period (2009–2012) was performed. 41 patients were included in the study, with placement of 48 SEMS. Improvement in dysphagia, survival and complication rates were the main outcome measures. <h3>Results</h3> 21 patients underwent radiologically guided placement, 20 for oesophageal cancer, 14 male, median age 78 years. 20 patients underwent endoscopically guided placement, 17 for oesophageal cancer, 8 male, median age 80.5 years. Disease stage was similar in both groups, with metastases in 11/21 of the radiology group, and 10/20 of the endoscopy group. More patients in the radiology group had received prior radiotherapy (13 vs 8). Significant improvement in dysphagia was similar in both groups (14/21 radiology vs 14/20 endoscopy, p = 0.82). There was no significant difference in median survival after stenting (135 vs 116 days, p = 0.98), or major 30 day complications defined as perforation, recurrent dysphagia or death (5 in both groups). <h3>Conclusion</h3> Direct vision endoscopic SEMS placement was as effective as radiological guidance for dysphagia palliation at our institution, with a similar mortality and complication rate. This provides further evidence for the role of direct vision endoscopic SEMS placement in palliation of malignant dysphagia. <h3>Reference</h3> Wilkes EA <i>et al</i>. Insertion of expandable metallic stents in esophageal cancer without fluoroscopy is safe and effective: a 5 year experience. <i>Gastrointest Endosc.</i> 2007 May;65:923–9 <h3>Disclosure of Interest</h3> None Declared.
Abstract 2109: Mir-125b confers the resistance of cancer cells to Taxol through suppression of Bak1
Authors: Ming Zhou, Yuhua Zhao, Yan Ding, Hao Liu, Zixing Liu, Yaguang Xi, Wei Xiong, Guiyuan Li, Jianrong Lu, Oystein Fodstad, Adam I. Riker, Ming Tan
Journal: Cancer Research (2010)

Abstract Paclitaxel (Taxol) is one of the most effective chemotherapeutic agents for treatment of cancer patients. Despite impressive initial clinical responses, the majority of patients will eventually develop some degree of resistance to Taxol-based therapy. The mechanisms underlying cancer cells resistance to Taxol are not fully understood. microRNA (miRNA) has emerged to play important roles in tumorigenesis and drug-resistance. However, the interaction between the development of Taxol resistance and miRNA has not been previously explored. In this study, we utilized a miRNA array to screen differentially expressed miRNAs, comparing Taxol-resistant and their Taxol-sensitive parental cells, and investigated the role and mechanisms of miR-125b in Taxol resistance of breast cancer cells. We found that miR-125b was up-regulated in Taxol-resistant cells, with its overexpression causing a marked inhibition of Taxol-induced cytotoxicity and apoptosis, and a subsequent increase in the resistance of cancer cells to Taxol. Moreover, we demonstrated that Bak1 is a direct target of miR-125b in breast cancer cells, and down- regulation of Bak1 suppressed Taxol- induced apoptosis and led to an increased resistance to Taxol. Furthermore, restoring the expression of Bak1 by either miR-125b inhibitor or specific siRNA recovered Taxol sensitivity, overcoming miR-125-mediated Taxol resistance. Taken together, our data strongly supports a central role for miR-125b in conferring Taxol resistance through the suppression of Bak1 expression. This finding has important implications in the development of targeted therapeutics for overcoming Taxol resistance in a number of different tumor histologies. 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 2109.
973 MOLECULAR BASIS FOR HEPATIC MULTIDRUG RESISTANCE-ASSOCIATED PROTEIN 3 INDUCTION BY ETHYNYLESTRADIOL
Authors: M.L. Ruiz, J.P. Rigalli, A. Arias, S.S. Villanueva, C. Banchio, M. Vore, A.D. Mottino, V.A. Catania
Journal: Journal of Hepatology (2012)
Ureteral Leak After Renal Transplantation
Authors: R J Rosenberg, R T Schweizer, R P Spencer
Journal: Clinical Nuclear Medicine (1999)

In the course of radionuclide dynamic studies in 187 consecutive patients who had renal transplants, leakage from a ureter was identified in five cases (an incidence of less than 3%). Demonstrated patterns fell into three classes: 1) perirenal collection (n = 2), 2) peribladder activity (n = 2), and 3) downward dissection (n = 1 case). The sensitivity and specificity of the radionuclide study for detecting ureteral escape of urine after renal transplantation is unknown. However, this study suggests that both indices may be high.
AB1441-HPR Poorer postural control of patients with low back pain compared to a control group
Authors: C.M. Carmo, K.S. Takara, F.G. Santos, F.M.B. Souza, C.M. Siqueira, C. Tanaka
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Changes in postural control is an important alteration found in Patients With Low Back Pain (LBP). The compromised motor control of the trunk and the alteration of muscle recruitment lead to different strategies to postural recover and may predispose to the recurrence of pain (1). Recent studies showed that LBP have poor postural recovery and take longer to stabilize their posture after voluntary arm movement (2). Previous pilot study showed that postural adjustments after external perturbation are possible compromised in LBP. <h3>Objectives</h3> To analyze the compensatory adjustments after an unexpected external perturbation of patients with low back pain compared to a control group. <h3>Methods</h3> Twenty-nine patients with LBP comprised the LBP group, and 14 healthy, age-paired asymptomatic subjects comprised the control group (CG). Participants stood on a force plate, and 4% of the subjects’ body weight was applied via a pulley system to a belt around the subjects’ trunks. The center of pressure (COP) displacement was measured after the weight was unexpectedly released to produce a controlled postural perturbation followed by postural adjustment to recover balance. The subjects’ postural adjustments in eight subsequent intervals of one second (t1–t8), beginning with the moment of weight removal, were compared among intervals and between groups. A two-factor (2 groups by 8 intervals) ANOVA was applied to the data. A Tukey post-hoc test was applied for pairwise comparisons. The significance level was set at 0.05. <h3>Results</h3> The applied perturbation magnitudes were the same for both groups, as no difference was observed between the groups of COP in t1; COP of t1 (perturbation) was different of t2-t8 intervals (recovery intervals) for both groups. No differences were observed between-groups in recovery intervals. Within-group analysis showed that the COP of t2=t3 (p=0.41) t2=t4 (p=0.06), t2&gt; from t5 to t8 (p&lt;0.002 for all) and t3=t4=t5=t6=t7=t8 in the LBP. These results suggest that patients in this group reached their postural balance after t3. Within-group analysis showed that the COP of t2=t3=t4=t5=t6=t7=t8 in CG suggesting that asymptomatic subjects reached their postural balance after t2. <h3>Conclusions</h3> Patients with LBP demonstrated poorer postural control while undergoing to unexpected balance perturbations when compared with healthily subjects. <h3>References</h3> Mok NW, Brauer SG, Hodges PW. Changes in Lumbar Movement in People With Low Back Pain Are Related to Compromised Balance. SPINE 2010, 36(1): E45–E52 Mok NW, Brauer SG, Hodges PW. Postural recovery following voluntary arm movement is impaired in people with chronic low back pain. Gait &amp; Posture 2011, 34: 97–102 <h3>Disclosure of Interest</h3> None Declared
Treatment of the Syndrome of Inappropriate Secretion of Antidiuretic Hormone with Lithium Carbonate
Authors: Martin G. White, Christopher D. Fetner
Journal: New England Journal of Medicine (1975)

Lithium, an established inhibitor of antidiuretic hormone action, was used (as the carbonate salt) to treat a patient with the syndrome of inappropriate secreation of antidiuretic hormone. The patient was studied by balance technics, and after a stablized hyponatremic state developed, 0.9 g of lithium carbonate was administered daily. A prompt water diuresis ensued, with correctionof hyponatremia in two days. Discontinuation of the drug resulted in a gradual return of the hyponatremic state. No change in urinary cyclic AMP occurred during the period of lithium effect. Lithium carbonate may be an effective treatment for both the acute and the chronic forms of the syndrome.
Breast tumor evolution.
Authors: K Polyak, M Shipitsin, L Campbell, J Yao
Journal: Cancer Research (2009)

Abstract Abstract #PD1-1 Breast tumors are heterogeneous and composed of a variety of cell types with distinct genetic, epigenetic, and phenotypic profiles. However, the molecular basis underlying this intra-tumoral heterogeneity has not been defined. Models that attempt to explain this include the malignant stem cell hypothesis and the genetic diversity combined with clonal selection models. Both of these ideas have been investigated for a long time both in human tumors and in various model systems, leading to the accumulation of numerous findings that are used to support one or the other. Although the two models share some similarities, they explain tumor progression, therapeutic resistance, and recurrence in fundamentally different ways. Increasing data suggest that the cancer stem cell phenotype may just be a consequence of genetic and epigenetic events that occur in tumor cells and that it may change as tumors evolve. Furthermore, there may be differences among tumor types regarding the applicability of the cancer stem cell and clonal evolution models. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr PD1-1.
1285 HEPATIC PTEN DEFICIENCY TRIGGERS STEATOSIS DEVELOPMENT BUT IMPROVES GLUCOSE TOLERANCE BY INHIBITING HEPATIC GLUCONEOGENESIS AND INDUCING MUSCLE INSULIN HYPERSENSITIVITY
Authors: M. Peyrou, L. Bourgoin, C. Maeder, A. Caillon, F. Rohner- Jeanrenaud, M. Foti
Journal: Journal of Hepatology (2013)
Can Congress Make You Buy Broccoli? And Why That's a Hard Question
Authors: Wendy K. Mariner, George J. Annas, Leonard H. Glantz
Journal: New England Journal of Medicine (2010)

The continuing uncertainty over the constitutionality of the Affordable Care Act, illustrated by conflicting trial court rulings and scholarly commentaries, raises the question of why this constitutional question is so hard to answer. There are at least four reasons.