tbuckley/cabot-search huggingface dataset:
Abstract 2527: Aspirin and aspirin analogs on esophageal cancer
Authors: Rajagopal Sharada Kilari, Christopher J. Perry, Andrew Devitt, Stephen T. Safrany, Iain D. Nicholl
Journal: Cancer Research (2014)

Abstract Background Esophageal cancer is the eighth most common cancer seen worldwide and is the sixth most common cause of death from cancer. The UK alone has over 8,000 new cases of esophageal cancer every year. Epidemiological studies have shown that low-dose daily intake of aspirin can decrease the incidence of esophageal cancer. However, its use as an anti-cancer drug has been restrained because of its side effects exerted through inhibition of cyclooxygenase (COX) enzymes. In our study, we have investigated the effects of a number of novel aspirin analogs on esophageal cancer cell lines. Methods The effects of aspirin and its analogs on the viability of esophageal cancer cell lines were tested using the MTT assay. ApoSense and flow cytometric analysis were performed to examine whether aspirin analog-mediated tumor cell death is due to apoptosis or necrosis. Colorimetric assays measuring peroxidase component of cyclooxygenases were employed to screen aspirin analogs for COX inhibition. Results Our data suggests that the anti-proliferative property of certain aspirin analogs is greater than that of aspirin itself. Benzoylsalicylates and fumaroyl diaspirin were more effective than aspirin against the oe21 squamous cell carcinoma cells and oe33 esophageal adenocarcinoma cells. Flo-1 esophageal adenocarcinoma cells showed resistance to aspirin and most of the aspirin analogs other than the benzoylsalicylates. Both diaspirin and benzoylsalicylates inhibited metabolic activity in all these esophageal cells. However, apoptosis was induced in only a small proportion. We have also shown that these aspirin analogs do not appear to inhibit COX enzymes. Conclusion We have synthesized and characterized a number of novel aspirin analogs that are more effective against esophageal cancer cell lines than aspirin. These compounds do not exert their anti-proliferative effect through induction of apoptosis. Moreover, these analogs inability to inhibit COX enzymes suggests that they may cause fewer or no side effects compared to aspirin. Citation Format: Rajagopal Sharada Kilari, Christopher J. Perry, Andrew Devitt, Stephen T. Safrany, Iain D. Nicholl. Aspirin and aspirin analogs on esophageal cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2527. doi:10.1158/1538-7445.AM2014-2527
Performance on the Adult Rheumatology In‐Training Examination and Relationship to Outcomes on the Rheumatology Certification Examination
Authors: Kristine M. Lohr, Amanda Clauser, Brian J. Hess, Allan C. Gelber, Joanne Valeriano‐Marcet, Rebecca S. Lipner, Steven A. Haist, Janine L. Hawley, Sarah Zirkle, Marcy B. Bolster
Journal: Arthritis & Rheumatology (2015)

The American College of Rheumatology (ACR) Adult Rheumatology In-Training Examination (ITE) is a feedback tool designed to identify strengths and weaknesses in the content knowledge of individual fellows-in-training and the training program curricula. We determined whether scores on the ACR ITE, as well as scores on other major standardized medical examinations and competency-based ratings, could be used to predict performance on the American Board of Internal Medicine (ABIM) Rheumatology Certification Examination.Between 2008 and 2012, 629 second-year fellows took the ACR ITE. Bivariate correlation analyses of assessment scores and multiple linear regression analyses were used to determine whether ABIM Rheumatology Certification Examination scores could be predicted on the basis of ACR ITE scores, United States Medical Licensing Examination scores, ABIM Internal Medicine Certification Examination scores, fellowship directors' ratings of overall clinical competency, and demographic variables. Logistic regression was used to evaluate whether these assessments were predictive of a passing outcome on the Rheumatology Certification Examination.In the initial linear model, the strongest predictors of the Rheumatology Certification Examination score were the second-year fellows' ACR ITE scores (β = 0.438) and ABIM Internal Medicine Certification Examination scores (β = 0.273). Using a stepwise model, the strongest predictors of higher scores on the Rheumatology Certification Examination were second-year fellows' ACR ITE scores (β = 0.449) and ABIM Internal Medicine Certification Examination scores (β = 0.276). Based on the findings of logistic regression analysis, ACR ITE performance was predictive of a pass/fail outcome on the Rheumatology Certification Examination (odds ratio 1.016 [95% confidence interval 1.011-1.021]).The predictive value of the ACR ITE score with regard to predicting performance on the Rheumatology Certification Examination supports use of the Adult Rheumatology ITE as a valid feedback tool during fellowship training.
Diagnosis of congenital cystic adenomatoid malformation of the lung in newborn infants and children.
Authors: H A Heij, S Ekkelkamp, A Vos
Journal: Thorax (1990)

Seventeen patients were diagnosed as having congenital cystic adenomatoid malformation of the lung during 1970-88. One case was associated with congenital diaphragmatic hernia and the child died before operation. The other 16 children underwent successful surgery. The patients presented in one of three ways--with neonatal respiratory impairment (12 cases) requiring urgent diagnosis and treatment, with recurrent respiratory tract infections (3), and with pneumothorax (1). Diagnostic problems arose with the neonatal presentation. In four of the children laparotomy was performed for presumed diaphragmatic hernia; three of these children had right sided lesions. Congenital diaphragmatic hernia was excluded by contrast studies in a further two patients. Histological examination confirmed the diagnosis in all cases. The postoperative course was uneventful in all 16 patients. No long term impairment of pulmonary function was noted.
Mechanisms of Cell Protection by Heme Oxygenase-1
Authors: Raffaella Gozzelino, Viktoria Jeney, Miguel P. Soares
Journal: The Annual Review of Pharmacology and Toxicology (2010)

Heme oxygenases (HO) catabolize free heme, that is, iron (Fe) protoporphyrin (IX), into equimolar amounts of Fe(2+), carbon monoxide (CO), and biliverdin. The stress-responsive HO-1 isoenzyme affords protection against programmed cell death. The mechanism underlying this cytoprotective effect relies on the ability of HO-1 to catabolize free heme and prevent it from sensitizing cells to undergo programmed cell death. This cytoprotective effect inhibits the pathogenesis of a variety of immune-mediated inflammatory diseases.
Adjuvant lapatinib for women with early-stage HER2-positive breast cancer: a randomised, controlled, phase 3 trial
Authors: Paul E Goss, Ian E Smith, Joyce O'Shaughnessy, Bent Ejlertsen, Manfred Kaufmann, Frances Boyle, Aman U Buzdar, Pierre Fumoleau, William Gradishar, Miguel Martin, Beverly Moy, Martine Piccart-Gebhart, Kathleen I Pritchard, Deborah Lindquist, Yanin Chavarri-Guerra, Gursel Aktan, Erica Rappold, Lisa S Williams, Dianne M Finkelstein
Journal: The Lancet Oncology (2012)
Revalidation of the retired
Authors: G L W Bonney
Journal: Journal of the Royal Society of Medicine (2002)

As I shall later show, I am very much older than Sir John Rawlins and Dr E N Wardle, but I think that both of them are quite old enough to have discerned the motives for the General Medical Council's (GMC's) assault on retired doctors (May 2002 JRSM1,2). The GMC, having betrayed doctors and their patients by conniving in the subordination of the clinical/professional to the managerial ethos, is deeply concerned now to preserve its own existence. Retired doctors are an easy target at which the GMC can aim in order to show the Government its continuing zeal.

Fifteen months ago, I responded to the GMC's request for comment on its paper Revalidating Doctors, putting most of the points now made by Rawlins and Wardle. Of course I received neither reply nor acknowledgment, but in the course of my enquiries I learned that, in spite of previous letters and phone calls, the GMC could not get my address right. Even better: my date of birth was (perhaps still is) recorded as 1 January 1700—for technical reasons, I was later told. This is the quality of body that now proposes to judge us. Quis, as we say in this part of Buckinghamshire, custodiet ipsos custodes. Or, as we used to say in Praed Street, Mit der Dummheit kampfen Gotter selbst vergebens.
Angiotensin II increases periostin expression via Ras/p38 MAPK/CREB and ERK1/2/TGF-β1 pathways in cardiac fibroblasts
Authors: Li Li, Dong Fan, Cheng Wang, Jin-Yu Wang, Xiao-Bing Cui, Dan Wu, Yun Zhou, Li-Ling Wu
Journal: Cardiovascular Research (2011)

AimsAngiotensin II (AngII) is involved in extracellular matrix (ECM) accumulation contributing to heart failure. Periostin, a 90 kDa ECM protein, is a key regulator of cardiac fibrosis, and its expression is significantly higher in failing hearts. We determined the modulatory effect of AngII on periostin level and explored the possible signal transduction mechanism.
The impact of menopause on bone, zoledronic acid, and implications for breast cancer growth and metastasis
Authors: P. Hadji, R. Coleman, M. Gnant, J. Green
Journal: Annals of Oncology (2012)

Recent data from the AZURE, ABCSG-12, and ZO-FAST clinical trials have challenged our understanding of the potential anticancer activity of zoledronic acid (ZOL). Although the results of these studies may appear to be conflicting on the surface, a deeper look into commonalities among the patient populations suggest that some host factors (i.e. patient age and endocrine status) may contribute to the anticancer activity of ZOL. Indeed, data from these large clinical trials suggest that the potential anticancer activity of ZOL may be most robust in a low-estrogen environment. However, this may be only part of the story and many questions remain to be answered to fully explain the phenomenon. Does estrogen override the anticancer activity of ZOL seen in postmenopausal women? Are hormones other than estrogen involved that contribute to this effect? Does the role of bone turnover in breast cancer (BC) growth and progression differ in the presence of various estrogen levels? Here, we present a review of the multitude of factors affected by different endocrine environments in women with BC that may influence the potential anticancer activity of ZOL.
Efficacy of a Herbst mandibular advancement device in obstructive sleep apnea.
Authors: S E Eveloff, C L Rosenberg, C C Carlisle, R P Millman
Journal: American Journal of Respiratory and Critical Care Medicine (1994)

Treatment options for obstructive sleep apnea (OSA) may involve potential side effects or discomfort; nasal continuous positive airway pressure (CPAP) may not be tolerated by 25% of patients. We therefore sought to determine the efficacy of mandibular advancement as a treatment for OSA, and to investigate whether clinical and radiographic parameters can predict the response to this treatment. Sixteen male and 3 female subjects with documented OSA who had failed or been unable to tolerate nasal CPAP underwent baseline polysomnography and cephalometry, and were then fitted with a removable Herbst appliance to achieve forward mandibular advancement during sleep. All subjects then underwent a second cephalometric evaluation and polysomnography with the appliance in place. Fourteen of 15 subjects demonstrated significant improvement in the degree of OSA, based on the apnea-hypopnia index (AHI) (34.7 +/- 5.3 to 12.9 +/- 2.4 events/h, p < 0.002). Comparison of pre- and posttreatment cephalometric values revealed no significant change in the posterior airway space (PAS) despite a reduction in mean AHI. There was a significant decrease in the mandible-hyoid distance (MP-H) with treatment for the group as a whole. When the study population was evaluated on the basis of a successful response to mandibular advancement (posttreatment AHI < 10), the baseline MP-H was found to be significantly shorter in the responders than in nonresponders. MP-H after mandibular advancement was likewise shorter in responders than in nonresponders. In addition, the soft palate length (PNS-P) showed a significantly greater shortening in responders after treatment.(ABSTRACT TRUNCATED AT 250 WORDS)
Tumor-Infiltrating Myeloid Cells Activate Dll4/Notch/TGF-β Signaling to Drive Malignant Progression
Authors: Hidetaka Ohnuki, Kan Jiang, Dunrui Wang, Ombretta Salvucci, Hyeongil Kwak, David Sánchez-Martín, Dragan Maric, Giovanna Tosato
Journal: Cancer Research (2014)

Myeloid cells that orchestrate malignant progression in the tumor microenvironment offer targets for a generalized strategy to attack solid tumors. Through an analysis of tumor microenvironments, we explored an experimental model of lung cancer that uncovered a network of Dll4/Notch/TGF-β1 signals that links myeloid cells to cancer progression. Myeloid cells attracted to the tumor microenvironment by the tumor-derived cytokines CCL2 and M-CSF expressed increased levels of the Notch ligand Dll4, thereby activating Notch signaling in the tumor cells and amplifying tumor-intrinsic Notch activation. Heightened Dll4/Notch signaling in tumor cells magnified TGF-β-induced pSMAD2/3 signaling and was required to sustain TGF-β-induced tumor cell growth. Conversely, Notch blockade reduced TGF-β signaling and limited lung carcinoma tumor progression. Corroborating these findings, by interrogating RNAseq results from tumor and adjacent normal tissue in clinical specimens of human head and neck squamous carcinoma, we found evidence that TGF-β/Notch crosstalk contributed to progression. In summary, the myeloid cell-carcinoma signaling network we describe uncovers novel mechanistic links between the tumor microenvironment and tumor growth, highlighting new opportunities to target tumors where this network is active.
CD28 and CTLA-4 have opposing effects on the response of T cells to stimulation.
Authors: M F Krummel, J P Allison
Journal: The Journal of Experimental Medicine (1995)

The importance of the B7/CD28/CTLA-4 molecules has been established in studies of antigen-presenting cell-derived B7 and its interaction with the T cell costimulatory molecule CD28. CTLA-4, a T cell surface glycoprotein that is related to CD28, can also interact with B7-1 and B7-2. However, less is known about the function of CTLA-4, which is expressed at highest levels after activation. We have generated an antibody to CTLA-4 to investigate the consequences of engagement of this molecule in a carefully defined system using highly purified T cells. We show here that the presence of low levels of B7-2 on freshly explanted T cells can partially inhibit T cell proliferation, and this inhibition is mediated by interactions with CTLA-4. Cross-linking of CTLA-4 together with the TCR and CD28 strongly inhibits proliferation and IL-2 secretion by T cells. Finally, results show that CD28 and CTLA-4 deliver opposing signals that appear to be integrated by the T cell in determining the response to activation. These data strongly suggest that the outcome of T cell antigen receptor stimulation is regulated by CD28 costimulatory signals, as well as inhibitory signals derived from CTLA-4.
Recombinant adeno-associated virus serotype 4 mediates unique and exclusive long-term transduction of retinal pigmented epithelium in rat, dog, and nonhuman primate after subretinal delivery
Authors: Michel Weber, Joseph Rabinowitz, Nathalie Provost, Hervé Conrath, Sébastien Folliot, Delphine Briot, Yan Chérel, Pierre Chenuaud, Jude Samulski, Philippe Moullier, Fabienne Rolling
Journal: Molecular Therapy (2003)

We previously described chimeric recombinant adeno-associated virus (rAAV) vectors 2/4 and 2/5 as the most efficient vectors in rat retina. We now characterize these two vectors carrying the CMV.gfp genome following subretinal injection in the Wistar rat, beagle dog, and cynomolgus macaque. Both serotypes displayed stable GFP expression for the duration of the experiment (6 months) in all three animal models. Similar to the AAV-2 serotype, AAV-2/5 transduced both RPE and photoreceptor cells, with higher level of transduction in photoreceptors, whereas rAAV-2/4 transduction was unambiguously restricted to RPE cells. This unique specificity found conserved among all three species makes AAV-2/4-derived vectors attractive for retinal diseases originating in RPE such as Leber congenital amaurosis (RPE65) or retinitis pigmentosa due to a mutated mertk gene. To provide further important preclinical data, vector shedding was monitored by PCR in various biological fluids for 2 months post-rAAV administration. Following rAAV-2/4 and -5 subretinal delivery in dogs (n = 6) and in nonhuman primates (n = 2), vector genome was found in lacrymal and nasal fluids for up to 3–4 days and in the serum for up to 15–20 days. Overall, these findings will have a practical impact on the development of future gene therapy trials of retinal diseases.
Antipsychotic Drugs: Prolonged QTc Interval, Torsade de Pointes, and Sudden Death
Authors: A H Glassman, J T Bigger
Journal: American Journal of Psychiatry (2001)

The authors review the mechanisms and establish the risk of torsade de pointes and sudden death with antipsychotic drugs.They present a review of original concepts, the distinction between familial and drug-induced cases of torsade de pointes, and the recognition of the role of noncardiac drugs in torsade de pointes and sudden death. They review the evidence linking QTc interval prolongation, potassium channels, and torsade de pointes from both the long QT syndrome and drugs. They examine the risk for torsade de pointes from antipsychotic drugs and estimate the frequency of sudden death on the basis of epidemiological data in normal and schizophrenic populations.All drugs that cause torsade de pointes prolong the QTc interval and bind to the potassium rectifier channel, but the relationships are not precise. Prediction of torsade de pointes and sudden death can be improved by examining dose dependency, the percent of QTc intervals higher than 500 msec, and the risk of drug-drug interactions. Although sudden unexpected death occurs almost twice as often in populations treated with antipsychotics as in normal populations, there are still only 10-15 such events in 10,000 person-years of observation.Although pimozide, sertindole, droperidol, and haloperidol have been documented to cause torsade de pointes and sudden death, the most marked risk is with thioridazine. There is no association with olanzapine, quetiapine, or risperidone. Ziprasidone does prolong the QT interval, but there is no evidence to suggest that this leads to torsade de pointes or sudden death. Only widespread use will prove if ziprasidone is entirely safe. To date, all antipsychotic drugs have the potential for serious adverse events. Balancing these risks with the positive effects of treatment poses a challenge for psychiatry.
Cloning and Characterization of Two New Isoforms of the Rat Kidney Urea Transporter
Authors: D Casellas, S Benahmed, A Artuso, B Jover
Journal: Journal of the American Society of Nephrology (1999)

Chronic administration of N(G)-nitro-L-arginine methyl ester (L-NAME) to rats induces systemic hypertension and progressive development of preglomerular sudanophilic (SB+) lesions. This study investigates whether progression of SB+ lesion formation froin 4 to 6 wk of L-NAME treatment (20 mg/kg per d, orally) would be affected by 2 wk administration of either the angiotensin II type 1 receptor antagonist candesartan cilexetil (3 and 10 mg/kg per d) or the vasodilator hydralazine (15 mg/kg per d). Frequencies of arcuate arterial branches (ArcB), interlobular arteries (ILA), and afferent arterioles (AA) endowed with SB+ lesions were assessed on preglomerular vasculatures isolated after HCl maceration. Systolic BP (SBP, tail-cuff manometry) increased from a baseline of 125+/-2 to 185+/-4, and to 193+/-4 mmHg after 4 and 6 wk of L-NAME treatment, respectively. During the fourth- to sixth-week period, albumin excretion increased significantly from 3.7+/-1.1 to 52.5+/-22.4 mg/24 h. At that time, SB+ lesions affected 62+/-8, 61+/-8, and 13+/-4% of ArcB, ILA, and AA, respectively. Candesartan cilexetil dose dependently reduced SBP, albumin excretion, and lesion development. At the highest dose, SB+ lesions only affected 12+/-6, 15+/-7, and 1+/-1% of ArcB, ILA, and AA, respectively. Hydralazine similarly reduced SBP and albumin excretion, although frequencies of SB+ lesions appeared less affected along ArcB and ILA. In conclusion, progression of preglomerular SB+ lesion formation during L-NAME hypertension can be prevented by angiotensin II type 1 receptor blockade, partly through pressure-lowering effects.
HIV Prevalence and Predictors of Infection in Sex-Trafficked Nepalese Girls and Women
Authors: Jay G Silverman, Michele R Decker, Jhumka Gupta, Ayonija Maheshwari, Brian M Willis, Anita Raj
Journal: JAMA (2007)

Sex trafficking of girls and women is widespread across South Asia and is recognized as both a violent gender-based crime and major human rights violation. Inadequate empirical data exist to characterize this phenomenon and its related health consequences, such as human immunodeficiency virus (HIV) infection.To determine the prevalence of HIV infection among repatriated sex-trafficked Nepalese girls and women and to identify trafficking-related predictors of such infection.Medical and case records of 287 repatriated girls and women reporting being trafficked from Nepal for sexual exploitation and receiving rehabilitative services between January 1997 and December 2005 at a major nongovernmental organization were systematically reviewed in January 2006.Major Nepalese nongovernmental organization providing shelter and care to repatriated survivors of sex trafficking.Prevalence of and risk for HIV based on demographic characteristics and on trafficking- and prostitution-related experiences.Among 287 repatriated Nepalese sex-trafficked girls and women, 109 (38.0%) tested positive for HIV. Among those with complete documentation of trafficking experiences (n = 225), median age at time of trafficking was 17.0 years, with 33 (14.7%) trafficked prior to age 15 years. Compared with those trafficked at 18 years or older, girls trafficked prior to age 15 years were at increased risk for HIV (adjusted odds ratio [AOR], 3.70; 95% confidence interval [CI], 1.32-10.34), with 20 of 33 (60.6%) infected among this youngest age group. Additional factors associated with HIV positivity included being trafficked to Mumbai (AOR, 4.85; 95% CI, 2.16-10.89) and longer duration of forced prostitution (AOR, 1.02; 95% CI, 1.01-1.03; indicating increased risk per additional month of brothel servitude). In post hoc analyses, girls trafficked prior to age 15 years had increased odds of having been detained in multiple brothels (odds ratio [OR], 5.03; 95% CI, 1.96-12.93) and in brothels for a duration of 1 year or more (OR, 2.67; 95% CI, 1.12-6.33) vs those trafficked at 18 years or older.In this study, repatriated Nepalese sex-trafficked girls and women were found to have a high prevalence of HIV infection, with increased risk among those trafficked prior to age 15 years. Present findings demonstrate the need for greater attention to reducing and intervening in sex trafficking in South Asia, particularly among the very young.