tbuckley/cabot-search huggingface dataset:
Abstract 3461: RSK2 is a driver of estrogen receptor positive breast cancer
Authors: Katarzyna Ludwik, Deborah Lannigan
Journal: Cancer Research (2015)

Abstract For unknown reasons, high levels of active Ser/Thr protein kinase RSK in estrogen receptor α (ERα)-positive (ER+) breast cancer patients correlate with better responsiveness to anti-estrogen therapies. Investigation of these surprising observations led us to discover an unanticipated mechanism in which ERα controls RSK2 nuclear accumulation. RSK2 is retained in the nucleus by physical association with ERα and this interaction is disrupted by anti-estrogen treatment. Consistent with these findings, in primary human ER+ breast tissue organoids, 4-hydroxy-tamoxifen (4-OHT) drove export of RSK2 to the cytoplasm. Importantly, RSK2 nuclear accumulation is critical for the expression of the oncogene, cyclin D1. This conclusion is supported by the observations that a RSK2 mutant, which cannot accumulate in the nucleus, does not rescue cyclin D1 in cells silenced for endogenous RSK2. Analysis of RNAseq data shows that ERα and RSK2 cooperatively regulate a transcriptional program, which includes cyclin D1. The physiological relevance of these conclusions is supported by our observations that in ∼60% of ER+ breast cancer patients, active nuclear RSK correlates with ERα and cyclin D1 levels. Taken together, these findings suggest that responsiveness to endocrine-based therapy is driven by reduced RSK2 nuclear accumulation, which in turn reduces expression of cyclin D1 and of other tumor-promoting effectors. Based on these observations we hypothesized that nuclear RSK2 cooperates with ERα and is a physiologically relevant driver of ER+ breast cancer. To test this hypothesis we generated a transgenic mouse model in which the MMTV promoter controls expression of RSK2 fused with the nuclear localization signal (NLS) of SV40. Strikingly, in ∼50% of transgenic mice forced nuclear accumulation of RSK2 in the mammary gland caused hyperplasia and ductal carcinoma in situ (DCIS). These results are the first demonstration that RSK2 can drive proliferation and transformation in vivo. Transgenic animals had a 4-fold increase in the number of cyclin D1 expressing cells and a 6-fold increase in Ki67 levels. Surprisingly, in vivo expression of nuclear RSK2 expanded the population of ER+ cells. These results demonstrate, for the first time, that nuclear RSK2 drives the amplification of the cell population relevant to ER+ breast cancer. In agreement with these observations we found that overexpression of ERα in the mouse mammary gland expands exclusively, by ∼3 fold, the cell population that co-expresses ERα and active nuclear RSK. These results further support our hypothesis that RSK2 cooperates with ERα and is an important drug target for ER+ breast cancer. Citation Format: Katarzyna Ludwik, Deborah Lannigan. RSK2 is a driver of estrogen receptor positive breast cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3461. doi:10.1158/1538-7445.AM2015-3461
Relationships Between Sinus Rhythm, Treatment, and Survival in the Atrial Fibrillation Follow-Up Investigation of Rhythm Management (AFFIRM) Study
Authors: Scott D Corley, Andrew E Epstein, John P DiMarco, Michael J Domanski, Nancy Geller, H Leon Greene, Richard A Josephson, Joyce C Kellen, Richard C Klein, Andrew D Krahn, Mary Mickel, L Brent Mitchell, Joy Dalquist Nelson, Yves Rosenberg, Eleanor Schron, Lynn Shemanski, Albert L Waldo, D George Wyse
Journal: Circulation (2004)

The AFFIRM Study showed that treatment of patients with atrial fibrillation and a high risk for stroke or death with a rhythm-control strategy offered no survival advantage over a rate-control strategy in an intention-to-treat analysis. This article reports an "on-treatment" analysis of the relationship of survival to cardiac rhythm and treatment as they changed over time.Modeling techniques were used to determine the relationships among survival, baseline clinical variables, and time-dependent variables. The following baseline variables were significantly associated with an increased risk of death: increasing age, coronary artery disease, congestive heart failure, diabetes, stroke or transient ischemic attack, smoking, left ventricular dysfunction, and mitral regurgitation. Among the time-dependent variables, the presence of sinus rhythm (SR) was associated with a lower risk of death, as was warfarin use. Antiarrhythmic drugs (AADs) were associated with increased mortality only after adjustment for the presence of SR. Consistent with the original intention-to-treat analysis, AADs were no longer associated with mortality when SR was removed from the model.Warfarin use improves survival. SR is either an important determinant of survival or a marker for other factors associated with survival that were not recorded, determined, or included in the survival model. Currently available AADs are not associated with improved survival, which suggests that any beneficial antiarrhythmic effects of AADs are offset by their adverse effects. If an effective method for maintaining SR with fewer adverse effects were available, it might be beneficial.
Mitral Regurgitation Augments Post-Myocardial Infarction Remodeling
Authors: Ronen Beeri, Chaim Yosefy, J. Luis Guerrero, Francesca Nesta, Suzan Abedat, Miguel Chaput, Federica del Monte, Mark D. Handschumacher, Robert Stroud, Suzanne Sullivan, Thea Pugatsch, Dan Gilon, Gus J. Vlahakes, Francis G. Spinale, Roger J. Hajjar, Robert A. Levine
Journal: Journal of the American College of Cardiology (2008)
Gastric Emphysema
Authors: Ulises Garza, Christopher Gayer
Journal: New England Journal of Medicine (2014)

A 10-month-old male infant weighing 7.34 kg (2nd percentile for age and sex) presented with a 4-day history of nonbilious, nonbloody emesis. He had a history of frequent nonbilious emesis and poor weight gain since birth.
Platelet [3H]imipramine binding in affective disorders: trait versus state characteristics
Authors: M Baron, A Barkai, R Gruen, E Peselow, R R Fieve, F Quitkin
Journal: American Journal of Psychiatry (1986)

Platelet [3H]imipramine binding (Bmax) was determined in 67 patients with major affective illness (33 euthymic bipolar, 34 depressed unipolar) and 58 normal control subjects. Bipolar patients had significantly lower Bmax values than did control subjects. The mean Bmax in the unipolar patients was lower than in the control subjects, but the difference was not statistically significant. Dissociation constant (Kd) values did not distinguish patients in either category from control subjects. The significantly lower Bmax in euthymic bipolar patients and the apparent state independence of Bmax in some but not all unipolar patients suggest that platelet imipramine binding may be a trait marker in a subset of affective disorders.
Predictive biomarker discovery and validation for the targeted chemotherapeutic ixabepilone
Authors: H. Lee, L. Xu, S. Wu, B. Paul, J. Baselga, A. Llombart, G. G. Steger, S. Galbraith, E. Clark
Journal: Journal of Clinical Oncology (2006)

3011 Background: Ixabepilone is a microtubule stabilizing agent with significant therapeutic value in breast cancer (BC) patients. To identify predictive biomarkers capable of identifying patients likely to receive optimal benefit from ixabepilone treatment, preclinical and clinical studies were carried out. Several biomarkers discovered using preclinical models were validated in a neoadjuvant BC clinical study ( CA163080 ) and one, estrogen receptor 1 (ER), was shown to double the pathological complete response (pCR) rate in patients treated with ixabepilone. To identify candidate sets of biomarkers that could further increase the pCR rate we have performed post-hoc analyses of the preclinical and clinical data. Methods: Eighteen BC cell lines were classified as sensitive or resistant (S/R) based on the IC50 values for ixabepilone treatment. Gene expression profiling of the BC cell lines was conducted and genes correlated with the S/R classification were identified using a k-Nearest Neighbors algorithm. Patients in clinical study CA163080 underwent a pretreatment core needle biopsy from which RNA was isolated and gene expression profiles generated (data available on 134 patients). Analyses using the preclinical and clinical markers were conducted using various statistical tools. Results: Several markers used in combination with ER were found to be capable of tripling the pCR to ixabepilone in CA163080. In addition to ER other predictive markers were identified that were as predictive as ER, including several genes whose expression is anti-correlated with ER and are part of the ER pathway. Finally, various sub-group analyses were performed and manifested the importance of clinical sample variation that needs to be considered for the analysis. Conclusions: Several single biomarkers identified from preclinical studies were validated in the clinical study CA163080 , demonstrating the utility of this approach. Such markers can be used in combination to better identify patients likely to respond to ixabepilone in future clinical trials. Furthermore, molecular response markers that can be tied to the mechanism of drug resistance can be used for further developing chemotherapy in drug development. [Table: see text]
Monitoring the safety of herbal remedies
Authors: D Sanders, N Kennedy, M W McKendrick
Journal: BMJ (1995)

Herbal remedies have a heterogeneous nature

EDITOR,--Herbal remedies are becoming increasingly popular with the public as they are perceived as being beneficial, free of side effects, and complementary to Western medicines.1 There have been a number of reports of hepatic toxicity involving different herbal products.2 3 Guy Vautier and R C Spiller report fulminant hepatic failure due to a Chinese herbal remedy …
Phase II study of neoadjuvant therapy with epirubicin and docetaxel for women with locally advanced breast cancer
Authors: J. L. Holter, A. Tfayli, S. Venkattapa, A. Bova, O. Howard
Journal: Journal of Clinical Oncology (2005)

881 Background: Women with locally advanced breast cancer are at high risk for tumor recurrence and death from their disease. The primary objective of this study was to assess the efficacy and safety of combination chemotherapy with Epirubicin and Taxotere (ET) given both neoadjuvantly and adjuvantly to women with locally advanced breast cancer. Secondarily we will assess survival outcome measures as data matures. Methods: Eligible patients were breast cancer patients with T3-T4 lesions, and those with T2 lesions that the surgeon felt that neoadjuvant therapy is needed for breast conservation. Patients were given 4 cycles of Epirubicin 75mg/m2 and Docetaxel 75mg/m2 intravenously every three weeks. Growth Factors (Filgrastim or Pegfilgrastim) were routinely given. RECIST criteria were used to assess response. Women with a response received 4 additional cycles of ET as adjuvant therapy. Results: Sixteen patients were enrolled from February 2003 to September 2004. Mean age was 50 (range 35–63). Average tumor size was 4.8cm, with 10/16 patients with clinically evident nodal disease. Clinical response and pathologic response rates were 68.75%. One of 16 (6.25%) had a pathological CR. Nodal downstaging was evident in 31.25% of patients, and T score was downstaged in 50%. Pathological response in subpopulations was as follows: Premenopausal 85.71%, her-2/neu positive 83.33%, receptor negative 71.43%, receptor pos 77.78%. Grade 3–4 neutropenia was recorded in 2 of 16 patients, with 1 treatment related death secondary to presumed sepsis in cycle 3. One patient had grade III fatigue. Cardiac changes were noted in 1 of 16 patients, with 10% drop in EF, but maintenance within the normal range. Common grade I and II toxicities were nausea, diarrhea, and fatigue. Survival data are not mature yet. Conclusions: Combination neoadjuvant therapy with docetaxel and epirubicin provides a feasible and effective choice for patients with locally advanced breast cancer. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Amgen, Pfizer, Aventis, Sanofi, Genentech Amgen, Pfizer, Aventis, Sanofi, Genentech, Pfizer, Speaker’s Bureau
Abstract 2765: Maintenance of Improvement in 6-Minute Walk Distance with Long Term Bosentan Treatment: Results of the BREATHE-1 Open-Label Extension Study
Authors: David B Badesch, Robyn J Barst, Nazzareno Galie, Carol M Black, Lewis J Rubin
Journal: Circulation (2006)

BACKGROUND: Bosentan, an oral dual endothelin receptor antagonist, is indicated for use in patients with functional class (FC) III and IV pulmonary arterial hypertension (PAH). The aim of this open...
Phase II study of capecitabine, irinotecan, and celecoxib in advanced colorectal cancer
Authors: B. F. El-Rayes, A. F. Shields, U. Vaishampayan, L. Heilbrun, T. Bekaii-Saab, M. M. Zalupski, P. A. Philip
Journal: Journal of Clinical Oncology (2004)

3766 Background: The cyclooxygenase-2 (COX-2) enzyme is overexpressed in the majority of colorectal cancers. Inhibition of the COX-2 enzyme can sensitize colorectal cancer cells to the apoptotic effects of chemotherapeutic agents and block angiogenesis. This phase II study was undertaken to determine the effects of adding celecoxib to capecitabine and irinotecan regimen. Methods: The primary objective was to estimate the objective response rate of patients with metastatic colorectal cancer treated with irinotecan, capecitabine, and celecoxib. Previously untreated patients, except for adjuvant therapy, with metastatic colorectal adenocarcinoma were eligible for this study. Patients received irinotecan 70 mg/m2 on days 1 and 8, and capecitabine 2,000 mg/m2/day from day 1 to 14 of a 21-day cycle. Celecoxib was administered at a dose 400 mg twice-daily starting day –7 until termination from study. Results: A total of 23 patients (median age 58 years) were enrolled on the study. Median performance status was 1. A total of 97 cycles (range 0–12) were administered. In an intention to treat analysis, objective response and stable disease were seen in 41% (90% CI; 0.24–0.60) and 27%, respectively. Objective response rate in the 17 patients evaluable for response was 53%(90% CI; 0.31–0.72). No treatment related deaths were observed. The only grade 3/4 toxicity was diarrhea (22%). Two patients developed grade 2 hand-foot syndrome and one patient developed grade 3 neutropenia. Only 1 patient was hospitalised for grade 4 diarrhea. Conclusion: Celecoxib can be safely administered in combination with irinotecan and capecitabine. The inclusion of celecoxib appears to significantly reduce the toxicity profile of this regimen, especially with respect to the hand-foot syndrome, myelosuppression and mucositis. These results suggest that this triple regimen has an optimum therapeutic index in metastatic colorectal cancer. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Eli Lily
Abstract 2290: Assessment of Left Ventricular Torsion Using Two Dimensional Speckle Tracking Echocardiography: Comparison with Tagged Cardiac Magnetic Resonance.
Authors: Celine Goffinet, Fabien Chenot, Patrick Montant, David Vancraeynest, Anne-Catherine Pouleur, Jean-Benoît le Polain de Waroux, Agnès Pasquet, Bernhard Gerber, Jean-Louis Vanoverschelde
Journal: Circulation (2007)

Background. LV torsion from helically oriented myofibers is a key parameter of cardiac performance. Until now, LV torsion could only be assessed using tagged cardiac magnetic resonance (cMR). Because of its high spatial and temporal resolution, speckle tracking echocardiography (STE) could be an alternative to cMR. STE offers the opportunity to track myocardial motion independently of both cardiac translation and angle-dependency. The aim of this study was to evaluate the accuracy and reproducibility of STE for the estimation of LV torsion using cMR as the reference standard. Methods . Ten controls and 43 patients with a variety of cardiac disease underwent cMR and STE on the same day. STE datasets were analyzed using a prototype version of the 2DQ QLab software that allows to track speckles on a frame by frame basis in the endocardium and epicardium, and to derive LV torsion and twisting velocities. Care was taken to analyze cMR and STE data on similar short-axis slices, matched on basis of their end-diastolic internal dimensions. Inter- and intraobserver variabilities were estimated by two blinded observers for 20 patients. In 5 volunteers STE and cMR were repeated twice to assess test-retest reproducibility. Results . Measurements of endocardial, midwall and epicardial torsion by cMR and STE did not differ significantly from each other (12.6 ± 5.9° vs. 12.5 ± 5.6°, 10.7 ± 4.7° vs. 9.7 ± 4.1°, and 8.9 ± 4.1° vs. 8.5 ± 3.8°, all p=ns) and were highly correlated (r=0.96, 0.88 and 0.79), with only small intertechniques biases (0.11 ± 3.4°, 0.98 ± 4.7° and 0.4 ± 5.28°). Peak twisting velocities, obtained by deriving systolic torsion over time, were also similar between cMR and STE (54 ± 18°/s and 63 ± 23°/s, p=ns) and were highly correlated (r=0.74). The intra- and interobserver agreement for peak LV torsion measurements, assessed by the intraclass correlation coefficient, was equally good for cMR (ICC=0.98 and 0.96; bias 0.3 ± 2.9 and 0.65 ± 3.1°) and for STE (ICC=0.98 and 0.96; bias 0.05 ± 2.8 and 0.13 ± 4.7°). Test-retest reproducibility was also excellent. Conclusions . Our data show that, compared to cMR, STE allows LV torsion to be accurately and reproducibly measured. This should make LV torsion assessment more available in clinical and research cardiology.
Abstract P55: Brief Bedside CPR Skill Debriefing and Automated Corrective Feedback During Simulated Pediatric Cardiac Arrest
Authors: Robert M Sutton, Dana Niles, Peter Meaney, Richard Aplenc, Ben French, Benjamin S Abella, Evie Lengetti, Robert A Berg, Mark A Helfaer, Vinay Nadkarni
Journal: Circulation (2009)

Introduction: Rescuers have difficulty delivering high quality CPR. Defibrillator automated corrective feedback and code team debriefing have improved CPR quality and outcomes in adult studies. Hyp...
All-transretinoic acid followed by intensive chemotherapy gives a high complete remission rate and may prolong remissions in newly diagnosed acute promyelocytic leukemia: a pilot study on 26 cases
Authors: P Fenaux, S Castaigne, H Dombret, E Archimbaud, M Duarte, P Morel, T Lamy, H Tilly, A Guerci, F Maloisel
Journal: Blood (1992)
Abstract 16413: Mutation Specific QTc Variance in Congenital Long QT Syndrome: A Clinical Predictor of Cardiac Events
Authors: Andrew M Mathias, Ilan Goldenberg, Arthur Moss
Journal: Circulation (2011)

Background: Multiple ion channel mutations account for the congenital Long QT Syndrome (LQTS). However, among carriers of the same mutation, the individual QTc may vary widely. Currently neither th...
P0825 : Varying efficacy of sofosbuvir treatment regimens in real life settings
Authors: E. Huchet, C. Galanakis, B. Trottier, M. Poliquin, S. Lavoie, D. Longpré, S. Vézina, C. Bédard, N. Machouf, R. Thomas
Journal: Journal of Hepatology (2015)
Appropriateness of colonoscopy in Europe (EPAGE II) – Surveillance after polypectomy and after resection of colorectal cancer
Authors: C. Arditi, J.-J. Gonvers, B. Burnand, G. Minoli, D. Oertli, F. Lacaine, R. Dubois, J.-P. Vader, S. Schusselé Filliettaz, I. Peytremann-Bridevaux, V. Pittet, P. Juillerat, F. Froehlich
Journal: Endoscopy (2009)

See also: Commentaire de "Retour vers le futur: EPAGE II" (6 articles), pp. 200Endoscopy 2009; 41(03): 388-390DOI: 10.1055/s-0032-1306673
Mutations of the CD40 Ligand Gene and Its Effect on CD40 Ligand Expression in Patients With X-Linked Hyper IgM Syndrome
Authors: Kuniaki Seyama, Shigeaki Nonoyama, Ingvild Gangsaas, Diane Hollenbaugh, Henry F. Pabst, Alejandro Aruffo, Hans D. Ochs
Journal: Blood (1998)
Abstract 693: Right Ventricular Dilation in Patients with Mild and Moderate Heart Failure: Implications in Morbidity and Mortality
Authors: Christos V Bourantas, Huan P Loh, Alan S Rigby, Thanjuvar Bragadeesh, Elena I Lukaschuk, Scot Garg, Ann C Tweddel, Farqad M Alamgir, Nikolay P Nikitin, Andrew L Clark, John G Cleland
Journal: Circulation (2008)

Objectives: To investigate the prognostic impact of right ventricular (RV) morphology in patients with mild and moderate heart failure. Methods: 80 normal subjects and 401 consecutive patients with left ventricular (LV) ejection fraction (EF)&lt; 45%, on optimal treatment, underwent cardiac magnetic resonance imaging (C-MRI). The LV and the RV borders were detected from the short axis contiguous slices and drawn manually. Body surface area was used to index (I) the LV and RV mass (M) and volumes (V) measured at end-diastole (ED) and end-systole (ES). The indexed volumes were then used to calculate the LV and RV EF. RV dilatation was defined as mean RVESVI+2*SD in normal subjects. Results: 21 patients had incomplete data and excluded from the analysis. The median age for the remaining patients was 71 years and 86% were men. 77% had ischaemic heart disease and 78% had NYHA I/II breathlessness. The median LVEF was 33% and the RVEF 43%. 286 (75%) patients had normal and 94 (25%) dilated RV. Patients with RV dilation were more often male (92% vs. 84%, p=0.036), had lower systolic blood pressure (120mmHg vs. 129mmHg, p=0.003), and were more likely to have NYHA breathlessness III/IV (30% vs. 18%, p=0.006). Patients with normal RV had higher LVEF (34% vs. 31%, p=0.015), smaller LVEDVI (115ml/m 2 vs. 137ml/m 2 , p&lt;0.0001) and LVESVI (77ml/m 2 vs. 92ml/m 2 , p&lt;0.0001) and were more likely to tolerate β-blockers (91% vs. 74%, p=0.002). Patients were followed up for 45±22months. During that time, there were no significant differences between the two groups regarding the reasons for admissions and the time that they spent to the hospital. Within that time 108 patients died [35 (37%) with dilated and 69 (24%) with normal RV; log-rank=8.404, p=0.004]. In multivariable Cox regression model, including 15 variables only increasing RVESVI (HR: 1.009, 95%CI: 1.000–1.017; p=0.043), the presence of ischaemic heart disease (HR: 2.186, 95%CI: 1.049–4.557; p=0.037) and the presence of peripheral vascular disease (HR: 1.674, 95%CI: 1.036–2.705; p=0.037) were independent predictors of mortality but not LVESVI. Conclusions: RV dilation is a common finding in patients with mild and moderate heart failure and is associated with worse prognosis.
P1296 : Blocking NMDA receptors prolongs survival in rats with acute liver failure by dual protective mechanisms in kidney and brain
Authors: O. Cauli, A. Gonzalez-Usano, A. Cabrera-Pastor, C. Gimemez-Garzo, A. Ruiz-Sauri, V. Hernandez-Rabaza, A. Agusti, A. Urios, A. Miguel, I. Torregrosa, C. Carda, C. Montoliu, V. Felipo
Journal: Journal of Hepatology (2015)
Abstract 17130: Lipids, Lipoprotein Subclasses, and Ankle Brachial Index in the Multi-Ethnic Study of Atherosclerosis
Authors: Christopher T Sibley, Aditya Jain, Pamela Schreiner, Ann M O'Hare, Joao A Lima, Michael Tsai, Gregory Burke, Criqui H Michael
Journal: Circulation (2010)
The Application of Positron Emission Tomography in Studies of Human Cerebral Glioma
Authors: D. G. T. Thomas
Journal: Neuro-Oncology (1991)

Positron Emission Tomography (PET) employs tracers labelled with the shortlived positron emitting isotopes of biologically important elements like oxygen, and carbon or the analogue of hydrogen, fluorine, to study non-invasively the pathophysiology of gliomas in man.