tbuckley/cabot-search huggingface dataset:
Abstract P1-01-15: Accuracy of sentinel lymph node in determining the requirement for second axillary surgeries in early breast cancer with retrospective application of the Z0011 criteria.
Authors: PS Waters, PJ Fennessy, D Alazawi, KJ Sweeney, MJ Kerin
Journal: Cancer Research (2012)

Abstract Background: Lymph node status is the most important prognostic marker in breast cancer management. The ACOSOG Z0011 trial reported no difference in survival in patients undergoing sentinel lymph node biopsy(SLNB) alone versus axillary lymph node dissection(ALND) in T1-T2 tumours with 1–2 positive lymph nodes. Aims: Whether sentinel lymph node biopsy was a true representative of axillary burden. We also addressed whether application of criteria from Z0011 trial would have prevented patients undergoing second axillary surgery. Methods: All patients with T1-T2 tumours undergoing sentinel node biopsy were included in our study (n = 1019). Analysis of our prospectively updated breast cancer database was performed. Minitab version 16.0 was used for statistical analysis. Results: 1019 SLNB procedures for T1 &amp; T2 tumours were performed over a 7 year period. 730 patients were reported as histologically negative and 289 were positive(&amp;lt;1 node = 194, &amp;gt;1 node = 95). Of the lymph node positive group, 223 patients progressed to axillary clearance. Staging of 149 patients remained unchanged with 74 patients being upstaged with having &amp;gt;2 lymph nodes reported as positive. 72 patients from the SLNB negative group also had an axillary clearance. 5 of these patients had further axillary disease with 1 patient being upstaged having &amp;gt;2 positive lymph nodes. With application of Z0011 criteria 220 patients would have avoided second axillary surgery. Conclusions: The accuracy of sentinel lymph node biopsy in determining tumour burden has been demonstrated. Furthermore application of Z0011 will have major cost savings for the health service with decreased patient stay and morbidity. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P1-01-15.
Abstract LB-261: A novel notch-AKT-NF-KB axis in triple negative breast cancer cells
Authors: Kandis V. Backus, Y Peng, C Hicks, S Kumar, G Kundu, A Pannuti, L Miele
Journal: Cancer Research (2012)

Abstract BACKGROUND: Basal-like and claudin-low are two major subgroups of triple-negative breast cancers (TNBC). The clinical subtype claudin-low is represented by MDA-MB 231 cells. The Notch and NF-κB signaling pathways are known to regulate proliferation, differentiation, and apoptosis by regulating the transcription of target genes. Both pathways are commonly active in TNBC. There is strong evidence for cross-talk between these pathways: We previously published that in cervical cancer cells, Notch-1 can activate NF-kB through nuclear IKKα. We published that Notch-1 can activate the estrogen receptor alpha (ERα), also through nuclear IKKα and the IKK signalosome in T-LL cells. However, the mechanism(s) of IKK downstream of Notch remain unknown. Notch1 is highly expressed in TNBC, and Notch ligands Jagged1 and 2 correlate with poor prognosis. IKKα (CHUK) is expressed in all subtypes of TNBC. We investigated whether Notch-1 can activate NF-kB in TNBC cells of claudin-low and basal like subtypes, whether this requires IKKα and how IKKα is activated. METHODS: We used Retroviral RNAi transduction of MDA-MB231 cells to establish Notch1 siRNA. ChIP (chromatin Immunoprecipitation), CoIP (co-immunoprecipitation), Western blot, luciferase reporter assays, co-culture MDA-MB 231 cells with LTK-JAG mouse fibroblasts, qPCR, xenograft tumors in nude mice. RESULTS: We have determined that phosphorylation of Akt is mediated through a non-canonical Notch signaling pathway and this is dependent on PTEN status. Unlike the canonical Notch pathway, Notch activation by Jagged1-expressing stroma cells leads to phosphorylation of Akt within minutes of contact between Jagged1-expressing stroma cells in PTEN wt, MDA-MB 231 cells through a non-transcriptional mechanism. Our data suggest that Notch complexes with PI3K subunits, p85 and p110, after ligand-mediated activation. Inhibition of Notch activity through GSIs (γ-secretase inhibitors) leads to decreased phosphorylation of Akt. Dominant-negative AKT abolishes IKKα phosphorylation. Additionally, the combination of the AKT inhibitor, perifosine and gamma-secretase inhibitor MRK-003 is synergistic in vitro and highly active in MDA-MB231 xenografts. CONCLUSIONS: Our findings suggest a novel non-canonical cross-talk mechanism including Jagged, Notch, AKT and IKKα connecting three major oncogenic pathways in TNBC: Notch, AKT and NF-kB. Moreover, our findings suggest that Akt inhibitors may be combined with GSI for therapeutic purposes. 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 LB-261. doi:1538-7445.AM2012-LB-261
Abnormal Biliary Lipid Composition in Cystic Fibrosis
Authors: Claude C. Roy, Andrée M. Weber, Claude L. Morin, Jean-Claude Combes, Daniel Nusslé, Albert Mégevand, Roger Lasalle, Liette Chartrand, Guy Lepage, André Fontaine
Journal: New England Journal of Medicine (1977)

Because of the increased incidence of gallstones in cystic fibrosis we compared biliary lipid composition in 26 patients with cystic fibrosis, seven children with cholelithiasis but no cystic-fibrosis and 13 controls. Eighteen of the cystic fibrosis group had cholecystograms, and only one had gallstones. In 14 patients with cystic fibrosis who had stopped taking pancreatic enzymes for one week molar percentage of lipid composition accounted for by cholesterol (mean ± S.E., 16.3±2.9) and saturation index (2.0±0.3) were comparable to values of the cholelithiasis group and higher (P<0.01) than those of controls. In 12 patients with cystic fibrosis taking pancreatic enzymes, molar percentage of cholesterol (8.6±1.7) and saturation index (1.0±0.1) did not differ from those of controls; in cystic fibrosis there was a preponderance of cholic over chenodeoxycholic acid both off (1.7±0.2) and on (1.9±0.3) therapy as compared to the cholelithiasis (0.7±0.1) and control (0.8±0.0) groups. The glycine/taurine ratio of conjugated bile acids was lower in enzyme-treated patients with cystic fibrosis (3.7±0.6) than in patients off treatment (6.4±1.0), but was higher (P<0.01) than in controls (1.8±0.2). Bile is lithogenic in untreated cystic fibrosis and responds to pancreatic enzymes. (N Engl J Med 297:1301–1305, 1977)
TREATMENT OF SEVERE AORTIC STENOSIS IN PATIENTS WITH END-STAGE RENAL DISEASE ON DIALYSIS
Authors: Jose Francisco Condado Contreras, Aneel Maini, Vinod Thourani, Chandan Devireddy, Bradley Leshnower, Kreton Mavromatis, Eric Sarin, James Stewart, Robert Guyton, Jessica Forcillo, Ateet Patel, Amy Simone, Patricia Keegan, Peter Block, Vasilis Babaliaros
Journal: Journal of the American College of Cardiology (2016)
Abstract 4015: Flavopiridol-induced upregulation of HtrA1 is associated with suppression of its negative transcriptional regulator WT-1 and with enhanced chemosensitivity
Authors: Tsuyoshi Ohta, Ashwani Khurana, Jacie Maguire, Xiaoping He, Jeremy Chien, Keith Bible, Viji Shridhar
Journal: Cancer Research (2011)

Abstract We previously identified serine protease HtrA1 as a down-regulated gene in epithelial ovarian cancer (EOC) that modulates cisplatin-induced cytotoxicity. However, the mechanism by which HtrA1 sensitizes cells to cisplatin-induced cytotoxicity remained unknown. We have shown previously that the pan-cyclin dependent kinase inhibitor flavopiridol (FP) sensitizes cells to cisplatin-induced cytotoxicity; we hypothesized that flavopiridol might therefore modulate the expression of pro-apoptotic proteins. Microarray data indicated that while flavopiridol treatment alone or in combination with cisplatin up-regulated HtrA1 expression by 2-3 fold (providing a means to upregulate HtrA1 expression), treatment with cisplatin alone had no effect. Interestingly, in searching for underlying mechanisms, we noted that WT-1 transcription factor binding elements that is present in HtrA1 promoter is down-regulated by flavopiridol in our microarray studies. Immunoblot analysis revealed that WT-1 is highly expressed in HtrA1-deficient OV167, OV202, PE04 and Ovcar3 cells but not in HtrA1-expressing SKOV3, TOV21G and PE01 cells, suggesting WT-1 negatively regulates HtrA1 expression in EOC. Immunoblot analysis showed FP treatment resulted in down-regulation of WT-1 with a corresponding increase in HtrA1 protein levels in OV202 cells. Additionally, stable down-regulation of WT-1 by short hairpin RNA (shRNA) in OV202 cells increased HtrA1 expression. Conversely, enhanced expression of full length WT-1 isoform in SKOV3 cells downregulated HtrA1 expression. Reporter assay showed that FP treatment upregulated HtrA1 promoter activity in OV202 cells. Reporter assay and chromatin immunoprecipitation experiments showed that WT-1 is specifically recruited to the HtrA1 promoter. Moreover, downregulation of WT-1 expression in OV202 cells increased cisplatin-mediated cytotoxicity as determined by both 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and clonogenic assays – an effect reversed by enhanced expression of HtrA1. Collectively, our studies demonstrate a linkage between the effects of flavopiridol on HtrA1 and its regulatory transcription factor WT-1 that appears in part to explain why flavopiridol has chemosensitizing properties 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 4015. doi:10.1158/1538-7445.AM2011-4015
Abstract 1507: Ectopic expresion of cathepsin G in mammary tumor cells and its role in tumor growth and osteolytic bone metastasis
Authors: Michelle L. Varney, Clint Gregory, Rakesh K. Singh
Journal: Cancer Research (2011)

Abstract Breast cancer has a high predilection to metastasize to the bone microenvironment. The resulting lesions are predominantly osteolytic and are associated with the resulting morbidity and mortality. We have demonstrated that tumor bone interaction plays an important role in osteolytic bone metastasis mediated by dysregulation of a unique set of genes. Among these genes several proteases have been found to be up-regulated at the tumor-bone interface, one of these is Cathepsin G, a serine protease. These proteases act as modulators between the tumor and stroma. Previously, we have shown that both malignant cells and osteoclasts at the TB-interface express higher levels of Cathepsin G, which is critical for osteolytic bone metastasis. The precise role of tumor and/or host-derived Cathepsin G in osteolytic bone metastasis is not known. In this report, we examined the contribution of tumor-derived Cathepsin G by testing the hypothesis that ectopic expression of Cathepsin G modulates malignant cell phenotype, osteoclast recruitment and activation, and osteolytic metastasis. We generated stable mammary tumor cell lines constitutively expressing Cathepsin G (Cl66-CTSG). Cathepsin G-expressing tumor cells showed diminished in vitro cell proliferative potential and in vivo mammary fat pad tumor growth as compared to vector control transfected Cl66-CMV cells. We demonstrated that Cathepsin G-overexpressing tumor cells induced osteoclast activation and differentiation in vitro and tumor-induced osteolysis in vivo. Our data suggest that tumor-derived Cathepsin G might have distinct tumor modulating activities in the bone microenvironment by regulating cell proliferation and osteoclast recruitment and activation. 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 1507. doi:10.1158/1538-7445.AM2011-1507
RELATIONSHIP OF SMOKING WITH MYOCARDIAL INJURY AND CLINICAL OUTCOME IN PATIENTS UNDERGOING MECHANICAL REPERFUSION FOR ST-ELEVATION MYOCARDIAL INFARCTION
Authors: Sebastian Reinstadler, Charlotte Eitel, Georg Fuernau, Suzanne de Waha, Steffen Desch, Bernhard Metzler, Gerhard Schuler, Holger Thiele, Ingo Eitel
Journal: Journal of the American College of Cardiology (2016)
Abstract C50: Dysregulation of microRNA-34a expression causes drug resistance to 5-FU in human colon cancer DLD-1 cells
Authors: Yukihiro Akao
Journal: Cancer Research (2011)

Abstract MiR-34a was identified as one of the downregulated microRNAs (miRs) in human colorectal cancer 5-fluorouracil (5-FU)-resistant DLD-1 cells compared with those in the parental DLD-1 cells. Exposure to 5-FU at 30 μM activated phosphoinositide 3-kinase (PI3K)/Akt signaling markedly from 12 h up to 48 h in the 5-FU-resistant cells compared with that in the parental cells and resulted in an overt difference in growth at those times. Furthermore, the expression of miR-34a in the 5-FU-resistant cells was sustained at a low level, whereas it was upregulated in the parental cells after the 5-FU treatment. Sirt1, which is one of the target genes for miR-34a and related to drug resistance, was strikingly upregulated in the 5-FU-resistant cells. The ectopic expression of miR-34a in the 5-FU-resistant cells inhibited growth, as in the parental cells, and attenuated the resistance to 5-FU through the downregulation of Sirt1 and E2F3. Moreover, the silencing of Sirt1 significantly canceled the resistance to 5-FU in the 5-FU-resistant cells. These findings suggest that miR-34a targeting the Sirt1 and E2F3 genes could negatively regulate, at least in part, the resistance to 5-FU in human colorectal cancer DLD-1 cells. 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 C50.
THU0314 Plasma IL-6 Levels Correlate with Ultrasound Measures of Disease Activity in Lupus Arthritis
Authors: E. Ball, A. Bell, M. Rooney
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> The role of specific cytokines in lupus arthritis has not been elucidated<sup>1</sup>. This is in stark contrast to rheumatoid arthritis (RA) where an abundance of research has culminated in an advancing era of novel biologic drugs. <h3>Objectives</h3> To analyse the cytokine profile in SLE patients with erosive, non-erosive arthritis and arthralgia as classified by ultrasound (US). <h3>Methods</h3> 50 SLE patients, and 40 RA patients had an US scan of their hand as per standardised protocols<sup>2-3</sup>. US scores per patient were expressed per joint and as a total '<i>ultrasound activity'</i> score, (sum of Power Doppler (PD) and Grey Scale Synovial Hypertrophy scores in all joints) and a total erosion score. SLE disease activity was assessed (BILAG and SELENA SLEDAI). Plasma levels of IL-6, TNF-alpha and BLyS were measured using sandwich ELISA kits (Quantikine® kits, R &amp; D). <h3>Results</h3> On the basis of the ultrasound results the SLE patients were divided into three groups, those with erosive arthritis (n = 24), those with non-erosive arthritis (n = 14) and those with a normal ultrasound scan (n = 12). CRP and IL-6 levels between the erosive lupus group and the RA group were not significantly different (p = 0.3 and p = 0.2 respectively). <h3>Conclusions</h3> This is the first study to examine levels of specific cytokines in a cohort of SLE patients stratified in terms of joint disease by ultrasound where the most significant finding is that IL-6 levels correlated with both clinical and ultrasound measures of arthritis disease activity. There is preliminary evidence that IL-6 blockade may be a potential treatment for SLE<sup>4</sup> and if arthritis specific outcome measures were included in future clinical trials more robust evidence could be generated. <h3>References</h3> Jacob N &amp; Stohl W. Cytokine disturbances in Systemic Lupus Erythematosus. Arthritis Research &amp; Therapy 2011; 13 (4): 244 Wakefield RJ et al. Musculoskeletal ultrasound including definitions for ultrasonographic pathology. J Rheum 2005;32(12):2485-87. Szkudlarek M et al. Interobserver agreement in ultrasonography of the finger and toe joints in rheumatoid arthritis. A &amp; R 2003;48(4):955-62. Illei G et al. Tocilizumab in systemic lupus erythematosus: data on safety...... A &amp; R 2010;62(2):542-52. <h3>Disclosure of Interest</h3> None Declared
INCIDENCE OF NEUROPSYCHIATRIC DISEASE IN THE DEMOBILIZED VETERAN
Authors: IRVING F. BURTON, MERRILL T. EATON, HERBERT G. MCMAHAN
Journal: American Journal of Psychiatry (1946)

1. The neuropsychiatric study of 10,000 separatees demobilized under the regulations existing during December 1945 and January 1946 showed that only 257 men (2.57%) had sufficient complaints to warrant a neuropsychiatric diagnosis. Of these, 51, or 0.51%, had a disorder sufficient in severity to cause them some degree of incapacity. 2. The lay press has overestimated the psychological problem of the veteran upon returning home. 3. Those cases whose neuropsychiatric disorders were precipitated by combat show a better response to reconditioning and had fewer complaints upon separation then those whose disorder was precipitated by factors other than combat. 4. The disorders discussed in this paper present a group for which hospital care is neither necessary nor desirable. The veteran has learned to accept the psychiatrist while in the Army and will expect skilled professional assistance within easy availability when out of the Army.
A Comparison of Immediate Coronary Angioplasty with Intravenous Streptokinase in Acute Myocardial Infarction
Authors: Felix Zijlstra, Menko Jan de Boer, Jan Hoorntje, Stoffer Reiffers, Johan Reiber, Harry Suryapranata
Journal: New England Journal of Medicine (1993)

Despite the widespread use of intravenous thrombolytic therapy and of immediate percutaneous transluminal coronary angioplasty for the treatment of acute myocardial infarction, randomized comparisons of the two approaches to reperfusion are lacking. We report the results of a prospective, randomized trial comparing immediate coronary angioplasty (without previous thrombolytic therapy) with intravenous streptokinase treatment.
Products at Risk
Authors: Gregory D. Curfman, Stephen Morrissey, Jeffrey M. Drazen
Journal: New England Journal of Medicine (2010)

In this issue of the Journal, we publish the results of a clinical trial investigating step-up control in adult patients with asthma whose disease was not well controlled by low-dose inhaled glucocorticoids.1 This study, which compared the utility of treating such patients with inhaled tiotropium bromide, inhaled salmeterol, or higher doses of inhaled glucocorticoids, was conceived and implemented by the National Heart, Lung, and Blood Institute's Asthma Clinical Research Network (ACRN). The study constitutes comparative effectiveness research, in which the products of a number of different companies are compared in a well-defined clinical setting. Simply put, the companies' products are . . .
Increased Need for Thyroxine in Women with Hypothyroidism during Estrogen Therapy
Authors: Baha M. Arafah
Journal: New England Journal of Medicine (2001)

Women with hypothyroidism that is being treated with thyroxine often need higher doses when they are pregnant. Whether this need can be attributed solely to estrogen-induced increases in serum thyroxine-binding globulin or whether other factors are involved is not known.
P17.42 * COMBINED TREATMENT OF PRIMARY MALIGNANT BRAIN TUMORS (ANAPLASTIC ASTROCYTOMAS - GRADE 111)
Authors: T. Izmailov, G. Panshin, M. Anashkina
Journal: Neuro-Oncology (2014)

Determination of prognostic factors influencing overall survival in high-grade brain Statistical analysis based on prognostic factors. The RSCRR from 2005-13 were treated 130 patients with brain tumors grade 3, the first phase of the combined treatment was surgery: total removal 28(21.5%) patients, subtotal 86(66.2%) patients, stereotacticbiopsy 16(12.3%). Women 68(52.3%), men 62(47.7%). Age patients from 40 to 60 years, 18 to 39 years (45.4%), 71-40years (54.6%). The average age 41.68 years, median 40.2. All patients were divided into classes RPA: I class 87(66.9%), class II 23(17.7%), class III 5(3.8%), class IV 15(11.5%). We used correlation analysis, estimates of cumulative survival by Kaplan-Meier and Coxregression analysis. The calculation of the immediate results of statistical analysis SPSS Reliable overall survival factors were age (r = 0,25; p <0,05) and the tumor size (r = 0,32; p 0,05). STB indicator of overall survival 60% of patients survived 5years, with the total removal of glioma100% over 5years (p = 0.004). low survival rates in patients >40years - less than 80% of the patients survived more than 5years, at a 40years was 9years, and <40years 13.6 years. 5year overall survival RPA I - 90%, RPA II III - 80%, VI - 18months. Overall survival of patients used radiotherapy with single dose 2-3 Gy (p = 0.975) Conducted data indicate the relevance to brain tumors grade 3 reliable overall survival factors, which include the age and size of the tumor. Important prognostic parameter for assessing survival is the amount of surgery performed, the basic principle is to remove as much tumor tissue as possible and maintaining healthy tissues.
Aspirin use and bleeding risk after endoscopic submucosal dissection in patients with gastric neoplasms
Authors: S-J. Cho, I. Choi, C. Kim, J. Lee, B.-H. Nam, M. Kwak, H. Kim, K. Ryu, J. Lee, Y.-W. Kim
Journal: Endoscopy (2012)

<b>Background and study aim: </b>The risk of bleeding after endoscopic submucosal dissection (ESD) in patients with early gastric neoplasms who do not discontinue aspirin for the procedure has not been established. We aimed to investigate whether post-ESD gastric bleeding is increased in patients who take aspirin. <b>Patients and methods: </b>Patients who underwent ESD for early gastric neoplasms at the National Cancer Center Hospital, Korea, between November 2008 and January 2011 were enrolled. The risk of post-ESD bleeding was evaluated using Poisson regression analysis. <b>Results: </b>We categorized 514 patients into three groups according to aspirin intake at the time of the procedure: patients who never used aspirin (n = 439), patients who interrupted aspirin use for 7 days or more (n = 56), and patients who continuously used aspirin (n = 19). Post-ESD bleeding occurred in 4.1 % (21 /514) overall, and was more frequent in continuous aspirin users (4 /19 [21.1 %]) than in those who never used aspirin (15 /439 [3.4 %]) (<i>P</i> = 0.006) and those with interrupted aspirin use (2 /56 [3.6 %]) (<i>P</i> = 0.033). Multivariate analysis showed that use of aspirin by itself was associated with post-ESD bleeding (relative risk [RR] 4.49; 95 % confidence interval [95 %CI] 1.09 – 18.38). The resumption of clopidogrel combined with aspirin use (RR 26.71, 95 %CI 7.09 – 100.53), and increased iatrogenic ulcer size (RR 1.52, 95 %CI 1.14 – 2.02), were significantly associated with post-ESD bleeding. <b>Conclusions: </b>Continuous aspirin use increases the risk of bleeding after gastric ESD. Aspirin use should be stopped in patients with a low risk for thromboembolic disease to minimize bleeding complications.