tbuckley/cabot-search huggingface dataset:
Abstract P4-15-06: Correlation between ERBB2 mRNA levels, HER2-dependence and susceptibility to trastuzumab in human breast cancer
Authors: Elda Tagliabue, Viola Regondi, Loris De Cecco, Serenella M Pupa, Manuela Campiglio, Maria Luisa Carcangiu, Sylvie Ménard, Tiziana Triulzi
Journal: Cancer Research (2015)

Abstract While results thus far demonstrate the clinical benefit of trastuzumab in breast cancer, some patients do not respond to this reagent. Identifying a robust clinical or molecular predictor of adjuvant trastuzumab benefit has proven challenging and even the most obvious candidate biomarker for a predictor of trastuzumab benefit, HER2 expression as assessed by immunohistochemistry (IHC) and/or fluorescence in situ hybridization (FISH), has proven to be surprisingly ambiguous in realizing benefit from the antibody. Results of a recent study that profiled expression of select genes in archived formalin-fixed, paraffin-embedded (FFPE) tumor blocks from a randomized study of breast cancer patients treated with adjuvant trastuzumab support a relationship between ERBB2/ESR1 mRNA levels and trastuzumab sensitivity. Based on that observation, we conducted whole-genome profiling by DASL technology of archival FFPE tumor blocks from 53 HercepTest 3+/2+ FISH-positive patients treated with adjuvant trastuzumab in our Institute; 308 genes were significantly associated with relapse-free survival by Cox proportional hazard model (α&amp;lt;0.005; permutation test p&amp;lt;0.01). We then developed a relapse risk 41-gene classifier (TRAR) able to discriminate cases mainly according to ERBB2 and ESR1 mRNA expression levels and to predict tumor relapse in both trastuzumab adjuvant and neoadjuvant settings. No correlation was found between ERBB2 mRNA and HER2 protein expression (the latter assessed by IHC on FFPE tumor sections using serial dilutions of anti-HER2 antibody), nor did HER2 protein expression correlate with relapse risk in these tumors. Analysis of HER2-amplified breast carcinoma cell lines revealed higher levels of ERBB2 mRNA in oncogene-addicted than in non-addicted cells in correlation with HER2 activation assed by Western blot but not with total HER2 protein amount. Moreover, ERBB2 mRNA expression levels in HER2-amplified breast carcinoma cells correlated with trastuzumab-mediated cellular cytotoxicity (ADCC) in vitro (r=0.96, p=0.038), whereas no correlation was found between ADCC and membrane-associated HER2. Together, our findings strongly suggest that ERBB2 mRNA, but not protein levels, mirror HER2 activity and thus oncogene addiction of tumor cells and susceptibility to trastuzumab in amplified HER2-positive tumors. Supported by AIRC. Citation Format: Elda Tagliabue, Viola Regondi, Loris De Cecco, Serenella M Pupa, Manuela Campiglio, Maria Luisa Carcangiu, Sylvie Ménard, Tiziana Triulzi. Correlation between ERBB2 mRNA levels, HER2-dependence and susceptibility to trastuzumab in human breast cancer [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P4-15-06.
Abstract 3811: Arsenic trioxide induces cell cycle arrest, apoptosis through interaction of DAXX and degradation of MDM2 in acute leukemia cells
Authors: Sanjay Kumar, Paul B. Tchounwou
Journal: Cancer Research (2015)

Abstract Arsenic trioxide (ATO) alone or combination with all trans retinoic acid (ATRA) has been successfully used in the treatment of all age group of acute promyelocytic leukemia (APL) patients. Recent human clinical trails result of ATO and their combination with ATRA shown complete remission in both de novo and relapsed APL patients. However, the detailed molecular mechanisms of its anti-leukemic action through cell cycle arrest and apoptosis are poorly known. We have used APL cell line and transgenic mice model to elucidate the anti-cancer properties of arsenic trioxide. We hypothesized that ATO arrests cell cycle and apoptosis through activation of p53 and interaction of death domain-associated protein (DAXX), which disrupted the MDM2-DAXX-HAUSP interactions. It also promoted MDM2 self-ubiquitination and degradation. To test the hypothesis, we used western blotting, confocal imaging and other molecular techniques to identify detailed cellular and molecular mechanisms of ATO action in APL cells and transgenic mice hepatocytes as well as bone marrow cells. We found that the expression levels of p53 and p21 increased significantly, whereas MDM2, DAXX and HAUSP decreased dose dependent manner. Our immunoprecipitation (IP) studies shown that they are well associated each other in cells and ATO disrupts associations. After 21 days treatment of ATO different doses (1.25, 2.5, 5.0 and 7.5 mg/kg body wt) in transgenic mice, we have collected liver tissue and isolated hepatocytes and bone marrow. In liver tissue, we found p53 nicely activated dose dependent ATO treated mice. On the basis of these findings, we conclude that ATO induces cell cycle arrest and apoptosis in APL cell line as well as mice hepatocytes through p53 activation, MDM2 self-ubiquitination and disruption of MDM2-DAXX-HAUSP interaction. It is novel target for treatment of APL patients through designing of new anti-leukemic drugs. Keywords: Arsenic trioxide, HL-60 cells, cell cycle arrest, apoptosis, mitochondrial pathway, Mice hepatocytes and bone marrow. Acknowledgements: This research was financially supported by National Institutes of Health NCRR Grant No. 5G12RR013459 and MIMHD Grant No. 8G12MD007581, through the RCMI-Center for Environmental Health at Jackson State University. Citation Format: Sanjay Kumar, Paul B. Tchounwou. Arsenic trioxide induces cell cycle arrest, apoptosis through interaction of DAXX and degradation of MDM2 in acute leukemia cells. [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 3811. doi:10.1158/1538-7445.AM2015-3811
Combining the two neonatal examinations
Authors: C. Harnden, T H H G Koh, C. M A Glazener
Journal: BMJ (1999)

Children born after intracytoplasmic sperm injection What do authors mean by control infants?Editor-Sutcliffe et al compare babies born through intracytoplasmic sperm injection with control babies (matched for social class, maternal education, region, and sex) born after unassisted conception. 1 In their table they give means, standard deviations, and 95% confidence intervals for the two groups separately.These confidence intervals tell us about the estimation of the mean in the population of which the babies are a random sample, which they are not.They tell us nothing about the comparison between the cases and controls.These controls have been chosen to be similar to the study babies in many ways; they are not a representative sample of babies.It is the difference between the study babies and the control babies that is of interest, and the confidence interval we should have is that for this difference in mean.We cannot work this out from the data given, because this is a paired study and we have unpaired standard deviations.All we have for the comparison is the implication, not actually stated, that the differences are not significant.What we should be given are confidence intervals that tell us how different the cases and controls are.
Studies on the purification of antihemophilic factor (factor VIII)
Authors: Oscar D. Ratnoff, Lawrence Kass, P. Dieter Lang
Journal: Journal of Clinical Investigation (1969)

A high degree of purification of antihemophilic factor was achieved by filtration of chylomicronpoor human plasma through columns of agarose. The final product contained, on the average, 67 units of antihemophilic activity per mg of protein, and was 3360-fold purified compared with the filtered plasma. The molecular weight of antihemophilic factor appeared to be at least two million. Preparations separated by gel filtration were contaminated with appreciable amounts of plasma thromboplastin antecedent (PTA), and traces of Christmas factor and Hageman factor, but no detectable fibrinogen was present. Similar fractions of plasma prepared from the blood of patients with classic hemophilia, von Willebrand's disease, or a circulating anticoagulant directed against antihemophilic factor contained, on the average, somewhat less protein than normal plasma; whether this difference was significant is not yet known. The purified fractions were partially stabilized by the addition of 1% gelatin. Adaptation of the technique of gel filtration to purification of antihemophilic factor for clinical use remains to be explored.
Respiratory events during sleep Amiens: 19th-20th November, 1987
Authors: NJ Douglas
Journal: European Respiratory Journal (1988)

N-[1-(S)-carboxy-3-phenylpropyl]-L-alanyl-L-proline (MK-422), is a potent angiotensin I-converting enzyme (ACE) inhibitor, but as a diacid is poorly absorbed in laboratory animals. Enalapril maleate, the monoethyl ester of MK-422, proved to be significantly better absorbed in both rats and dogs. Peak levels of radioactivity in plasma occurred in 30 min in rats and 2 hr in dogs after a single dose of 14C-enalapril maleate (1 mg/kg, po). Rats excreted 26% of the dose in the urine and 72% in the feces in 72 hr; dogs excreted 40% of the dose in the urine and 36% in the feces. After the intravenous dose, the presence of radioactivity in the feces of both species suggested that some biliary excretion had occurred. Absorption was estimated to be 34% in the rat and 61% in the dog. The major metabolite of enalapril maleate in dogs, accounting for 86% of the urine radioactivity, was identified as MK-422 by GC/MS. A procedure was developed for the quantitation of MK-422 and enalapril in plasma and urine by their inhibition of purified ACE. The assays showed that enalapril was absorbed intact in dogs and converted to MK-422 after absorption.
Interferon and Cancer Treatment
Authors: Robert M. Friedman
Journal: CA A Cancer Journal for Clinicians (1978)

It was discovered by Alec Isaacs, in England in about 1957.He was investigating the phenomenon of viral interference and came upon interferon; subsequent research established that interferon is a protein elaborated by animal cells, that it has anti-viral activity, and that it is usually species-specific.He also determined how to initiate anti-viral activity by applying interferon to cells in culture and to animals.
Intestinal Secretion Induced by Vasoactive Intestinal Polypeptide
Authors: Guenter J. Krejs, Ronald M. Barkley, Nicholas W. Read, John S. Fordtran
Journal: Journal of Clinical Investigation (1978)

The effect of vasoactive intestinal polypeptide (VIP) on intestinal water and electrolyte transport and transmucosal potential difference was investigated in the dog jejunum in vivo and compared to secretion induced by cholera toxin. Isolated jejunal loops were perfused with a plasma-like electrolyte solution. VIP (0.08 μg/kg per min) was administered directly into the superior mesenteric artery by continuous infusion over 1 h. From a dye dilution method, it was estimated that a mean plasma VIP concentration of 12,460 pg/ml reached the loops. VIP caused secretion of water and electrolytes; for example, chloride: control, 8 μeq/cm per h absorption; VIP, 92 μeq/cm per h secretion. A marked increase in transmucosal potential difference (control, −1.0 mV; VIP, −5.9 mV, lumen negative) occurred within 1 min after starting VIP infusion. Analysis of unidirectional fluxes showed increased plasma-to-lumen flux of sodium and chloride and decreased lumen-to-plasma flux of sodium. Chloride and bicarbonate were actively secreted against an electrochemical gradient. Although sodium secretion occurred down an electrochemical gradient, flux ratio analysis suggested a component of active sodium secretion. VIP caused a slight increase in protein output into the loops; light microscopy revealed capillary dilatation and closed intercellular spaces. The effect of VIP was readily reversible. Except for the delayed onset of secretion, the effect of cholera toxin was qualitatively similar to VIP; however, capillary dilatation and increased protein output were not noted with cholera toxin.
A phase I/II study of docetaxel in combination with doxorubicin HCI liposome injection in advanced androgen-independent prostate cancer
Authors: M. E. Martin, L. A. Ferguson, D. A. Williams, D. A. Laber
Journal: Journal of Clinical Oncology (2006)

14588 Background: There is no cure for men with AIPC. Recently two landmark studies demonstrated an improvement in survival for men with AIPC treated with docetaxel based chemotherapy. Doxorubicin is a very active agent against AIPC. Doxil is liposome-encapsulated doxorubicin with less toxicity. Methods: Objectives are to evaluate the efficacy and safety of DoxTax. A phase I dose escalation study was performed. Three cohorts according to the following dose escalation schedule were formed. In the absence of DLT, level 3 was the recommended dose for the phase II study. Response was assessed by size of measurable and non-measurable lesions (RECIST JNCI.2000), and PSA levels (JCO.1999). Toxicity was graded by the NCI CTCAE. Results: Eleven subjects with AIPC were enrolled and evaluated for toxicity and response. Total number of cycles administered: 59, median of 5.5 cycles/patient. Patient characteristics: Median age 67 years (53–81); prior hormonal manipulations 2 (1–2); prior chemotherapy 1 (0–2); ECOG performance status 1 (1–2); and median PSA 78 ng/ml (8.73–783). Objective response: Out of 11 subjects, four men (36%) achieved a reduction in PSA of &gt; 50%, while one (9%) achieved a &gt;80% PSA reduction, for an overall PSA response of 45%. Seven patients had measurable lesions. Using RECIST criteria, five of seven subjects maintained (SD). Palliative response: Nine subjects (82%) improved their ECOG performance status. Additionally, 8 men (73%) had decreased level of pain. Toxicity: No dose limiting toxicity occurred. One patient had grade 3 generalized weakness related to disease progression. Grade 1–2 adverse events were not related to the dose and included: 64% fatigue, 45% anemia, 18% neutropenia, alopecia, anorexia, vomiting, 9% each for nausea, thrombocytopenia, weakness, hand/foot, and neuropathy. Conclusions: DoxTax is a well-tolerated, easy to administer and effective therapy for patients with metastatic AIPC. Accrual to the phase II trial is ongoing. [Table: see text] [Table: see text]
HIV-1 infections with multiple founders are associated with higher viral loads than infections with single founders
Authors: Holly Janes, Joshua T Herbeck, Sodsai Tovanabutra, Rasmi Thomas, Nicole Frahm, Ann Duerr, John Hural, Lawrence Corey, Steve G Self, Susan P Buchbinder, M Juliana McElrath, Robert J O'Connell, Robert M Paris, Supachai Rerks-Ngarm, Sorachai Nitayaphan, Punnee Pitisuttihum, Jaranit Kaewkungwal, Merlin L Robb, Nelson L Michael, James I Mullins, Jerome H Kim, Peter B Gilbert, Morgane Rolland
Journal: Nature Medicine (2015)
An Integrated Pharmacogenomic Strategy for the Definition of Thalidomide Response Signatures in Presenting Cases of Multiple Myeloma.
Authors: Gareth J. Morgan, Matthew W. Jenner, Brian A. Walker, David C. Johnson, Paola A. Leone, Fiona M. Ross, Mark T. Drayson, Brian G. Van Ness, Brian G. Durie, Nicholas J. Dickens, J. Anthony Child, R.G. Owen, Faith E. Davies
Journal: Blood (2007)
HCA, an Immunoglobulin-Like Adhesion Molecule Present on the Earliest Human Hematopoietic Precursor Cells, Is Also Expressed by Stromal Cells in Blood-Forming Tissues
Authors: Fernando Cortés, Frédéric Deschaseaux, Nobuko Uchida, Marie-Claude Labastie, Annabelle M. Friera, Dongping He, Pierre Charbord, Bruno Péault
Journal: Blood (1999)
Quality of life and dissociation in anxiety disorder patients with histories of trauma or PTSD
Authors: M G Warshaw, E Fierman, L Pratt, M Hunt, K A Yonkers, A O Massion, M B Keller
Journal: American Journal of Psychiatry (1993)

The purpose of this analysis was to examine quality of life and dissociation in anxiety disorder subjects with histories of trauma, some of whom met criteria for posttraumatic stress disorder (PTSD). Subjects came from a prospective, longitudinal study of anxiety disorders. Information was gathered on role, social life, suicide attempts, psychiatric hospitalization, alcohol and substance abuse, depression, and dissociation. Subjects with PTSD had the worst functioning on all of the measures examined except social life. Those with histories of trauma but no PTSD differed from subjects who reported no history of trauma, primarily in high rates of alcoholism and minor depression. PTSD has severe effects on quality of life in virtually all spheres of life. The high levels of depression, suicide attempts or gestures, and alcohol abuse are of particular concern and show that trauma can have long-lasting effects.
Abstract 15583: Toll-Like Receptor 4 Knockout Preserves Cardiac Function in High Fat Diet-Induced Obesity
Authors: Nan Hu, Yingmei Zhang, Jun Ren
Journal: Circulation (2014)

Background: Toll-like receptor 4 (TLR4) is an innate proinflammatory mediator found in a wide variety of cell types including cardiomyocytes. The autophagy-lysosome pathway, a major pathway governing protein and organelle degradation and recycling, plays a pivotal role in maintaining cardiac homeostasis under physiological and pathological conditions. The aim of this study was to evaluate the impact of TLR4 knockout (TLR4 -/- ) on high fat diet (HFD)-induced cardiomyopathy and the underlying mechanisms involved, with a focus on inflammation and autophagy pathways. Methods: Wild type (WT) and TLR4 -/- mice were fed on low fat diet (LFD) or HFD for 12 weeks. Metabolic rate and glucose tolerance were measured in WT and TLR4 -/- mice at the end of fat diet intake. Echocardiographic, cardiomyocyte mechanical function, morphological feature, aconitase activity, ROS generation and immunoblotting were assessed. Results: TLR4 -/- did not prevent HFD-induced obesity and insulin resistance, as evidenced by body weight gain and glucose intolerance. In addition, there was little difference in metabolic parameters (V O2 , V CO2 , RER, energy expenditure and physical activity) between WT and TLR4 -/- mice fed with HFD. However, TLR4 -/- alleviated HFD-elicited cardiac hypertrophy and contractile dysfunction. HFD-feeding caused extensive mitochondrial injury and ROS generation, which were alleviated by TLR4 -/- . TLR4 -/- dramatically attenuated inflammation signaling (up-regulated p-IKβ, NF-κB and p-JNK) in the face of HFD intake. Cardiac autophagy was significantly suppressed by HFD, as evidenced by up-regulated p-mTOR, down-regulated p-AMPK, Atg5, Atg12, LC3BII, and up-regulated P62 in HFD-induced cardiomyopathy. Furthermore, in vitro study revealed that the TLR4 inhibitor-TAK-242 reconciled palmitic acid-induced cardiomyocyte autophagy and contractile anomalies. Conclusions: Our results suggested that TLR4 -/- does not prevent HFD-induced obesity and insulin resistance. However, TLR4 is a culprit factor for cardiac dysfunction following HFD intake. The cardioprotective effect of TLR4 -/- against HFD-induced cardiomyopathy is associated with attenuation of myocardial inflammation and recovery of cardiac autophagy activity.
Abstract 10694: Optimal Frequency and Acoustic Pressure for Sonothrombolysis with Microbubbles in a Flow System: Clinical Implications
Authors: Azzdine Y Ammi, Yan Zhao, Jonathan R Lindner, Thomas R Porter, Robert J Siegel, Aris Xie, Sanjiv Kaul
Journal: Circulation (2012)

BACKGROUND: Ultrasound exposure of microbubble (MB) contrast agents has been shown to lyse thrombus, yet characterization of the effect of acoustic pressure (AP) and frequency is incomplete. Our ai...
Abstract P285: Frequency of Sexual Activity the Year before Myocardial Infarction and Risk for Subsequent Cardiovascular Adverse Events: Results of a Long-Term Follow-Up Study
Authors: Dietrich Rothenbacher, Dhayana Dallmeier, Ute Mons, Wayne D Rosamond, Wolfgang Koenig, Hermann Brenner
Journal: Circulation (2015)

Introduction: Sexual activity (SA) is an important component of quality of life and of concern for many patients with myocardial infarction (MI). Available data showed that the frequency of SA decreased one year after an MI, however, the general patterns were relatively stable overall. Although SA may be a trigger of an MI in very few cases, the association between SA before MI and the onset of a subsequent adverse cardiovascular disease event (CVD-event) has not been evaluated so far. Hypothesis: Frequency of SA during the 12-months prior to an MI is not associated with risk of subsequent adverse CVD-event. Methods: Prospective cohort study in CHD patients aged 30-70 years undergoing an in-patient rehabilitation program after an incident MI due to CHD. SA frequency (including masturbation) during the 12-months prior to the MI was evaluated by means of a standardized questionnaire. A Cox-proportional hazards model was used to determine the association of frequency of SA on subsequent adverse CVD-events (nonfatal and fatal MI, stroke, cardiovascular death) during ten-year follow-up after adjustment for age, gender, school education, rehabilitation clinic, smoking status, history of diabetes mellitus, left-ventricular function HDL-cholesterol. Results and Conclusions: The mean age of the included 536 patients with an incident MI was 57.1 years (SD 8.6) at baseline, 85.8% were men. Self-reported SA in the 12-months before the MI was none for n=80, less than 1 time per month for n=25 (both grouped in one category), less than 1 time per week for n=136, and one or more times per week for n=295. Sexual more active patients were on average younger, more often men, had less often diabetes and a less severe coronary vessel disease. They were also more often physical active in leisure time compared to others. During ten-year follow up (median 9.97 years) n=100 adverse CVD-events occurred (overall 23.9 events per 1000 patient years). When compared to patients with less than one time SA per week (reference group) patients with at least one SA per week had a Hazard ratio (HR) of 0.49 (95% confidence interval (CI) 0.31-0.77) in the multivariable analysis; adding leisure time physical activity practiced 12-months prior to the MI into this final model did not change the results. Additional adjustment for Nt-proBNP level at baseline did not alter the result. In conclusion, a weekly SA activity pattern in the year prior to an acute MI is not associated with a higher risk for subsequent adverse cardiovascular events.
HIV-1 variability and viral load technique could lead to false positive HIV-1 detection and to erroneous viral quantification in infected specimens
Authors: Patricia Alvarez, Leticia Martín, Luis Prieto, Jacinta Obiang, Antonio Vargas, Pedro Avedillo, Pablo Rojo, Carolina Fernández McPhee, Agustín Benito, José Tomás Ramos, África Holguín
Journal: Journal of Infection (2015)