tbuckley/cabot-search huggingface dataset:
Abstract B7: microRNA regulation of cell viability and drug sensitivity in lung cancer
Authors: Liqin Du, Christopher DeSevo, Borkowski Robert, Baker Michael, Adi F. Gazdar, John D. Minna, Alexander Pertsemlidis
Journal: Cancer Research (2012)

Abstract Introduction: Lung cancer is the leading cause of cancer-related deaths, with the majority of deaths due to failed therapy from tumor drug resistance. Third-generation chemotherapeutic agents represent the standard first-line treatment for advanced small cell (SCLC) and non-small cell (NSCLC) lung cancer patients. Response rates are poor (20–40%) with a median survival of 8–10 months. Methods: In an unbiased and comprehensive approach, we have combined a high-throughput screening platform with a library of chemically synthesized microRNA mimics and inhibitors. We have used this platform to identify mimics and inhibitors that reduce cell viability in general, and those that specifically sensitize cells to taxanes. Results: We have identified several miRNAs for which over-expression or inhibition has a dramatic and selective effect on cell viability or drug response. We have demonstrated that miR-337-3p mimic sensitizes NSCLC cells to taxanes. By combining in vitro and in silico approaches, we identified STAT3 and RAP1A as direct targets that mediate the effect of miR-337-3p by enhancing taxane-induced arrest in the G2 phase of the cell cycle. We have also identified an inhibitor of miR-139-5p as a potent and selective regulator of SCLC cell viability. Inhibiting miR-139-5p decreases SCLC cell viability by over 80%, but has a minimal cytotoxic effect on that of NSCLCs or immortalized human bronchial epithelial cells. We are currently investigating the targets of miR-139-5p that mediate its effect on SCLC cell viability. Conclusion: We have identified miR-337-3p as a regulator of taxane sensitivity in NSCLC, and miR-139-5p as a modulator of viability in SCLC. Increasing levels of miR-337-3p and inhibiting miR-139-5p may therefore provide novel therapeutic tools for the treatment of NSCLC and SCLC lung tumors, respectively. Citation Format: Liqin Du, Christopher DeSevo, Borkowski Robert, Baker Michael, Adi F. Gazdar, John D. Minna, Alexander Pertsemlidis. microRNA regulation of cell viability and drug sensitivity in lung cancer [abstract]. In: Proceedings of the AACR Special Conference on Noncoding RNAs and Cancer; 2012 Jan 8-11; Miami Beach, FL. Philadelphia (PA): AACR; Cancer Res 2012;72(2 Suppl):Abstract nr B7.
Meta-analyses: how to read a funnel plot
Authors: P. Sedgwick
Journal: BMJ (2013)

Researchers undertook a meta-analysis to evaluate the relative short term safety of carotid endarterectomy compared with carotid artery stenting.1 Randomised controlled trials were included if they compared carotid endarterectomy with carotid artery stenting in patients with carotid artery stenosis (with or without symptoms). In total, 10 trials were identified that reported short term outcomes. The primary endpoint was mortality or stroke within 30 days of the procedure.

The total overall periprocedural risk of mortality or stroke was lower for carotid endarterectomy than for carotid artery stenting (odds ratio 0.67, 95% confidence interval 0.47 to 0.95; P=0.025). A funnel plot was presented (figure⇓). Egger’s test gave a P value equal to 0.932.



Funnel plot for the meta-analysis of the short term safety (periprocedural mortality or stroke) of carotid endarterectomy compared with carotid artery stenting



Which of the following statements, if any, are true?

Statements a and b are true, whereas c is false.

The meta-analysis investigated the relative short term safety of carotid endarterectomy compared with carotid artery stenting. Ten trials were identified …
Expression of the peripheral benzodiazepine receptor is decreased in skin cancers in comparison with normal skin
Authors: J. Morgan, A.R. Oseroff, R.T. Cheney
Journal: British Journal of Dermatology (2004)

Background The peripheral benzodiazepine receptor (PBR) is an 18-kDa protein receptor mainly found on the outer mitochondrial membrane of cells. The PBR plays a role in several cellular functions including haem synthesis, steroidogenesis, DNA synthesis, cell growth and differentiation, and apoptosis. PBR expression in normal skin correlates with proliferating, secretory and differentiated cellular structures. Increased or aberrant expression of PBR has been associated with aggressive behaviour in several tumour types including ovarian, colon and breast adenocarcinomas and glioblastoma. Objectives To determine whether changes in normal PBR distribution would be useful as markers for skin cancers or possible target sites for therapies such as photodynamic therapy (PDT), we used immunohistochemistry to evaluate PBR expression and distribution in normal and photodamaged skin (actinic keratoses), skin cancers (in situ and invasive squamous cell carcinomas and superficial, nodular, morphoeiform and mixed pattern basal cell carcinomas) and several benign epithelial proliferations. Methods A rabbit polyclonal antibody to a synthetic peptide fragment of the PBR was developed and characterized by enzyme-linked immunosorbent assay and Western blot analysis. The antibody was used to stain formalin-fixed and paraffin-embedded tissue samples (n = 157) by a routine avidin–biotin immunohistochemical technique. Sections were evaluated for antibody localization, distribution (0–4+) and reaction intensity (negative to strong). Results Normal skin stained with a strong homogeneous positive reaction (3–4+) in the spinous and granular layers (with a gradient corresponding to increasing differentiation), the pilosebaceous units, eccrine gland ducts, endothelial cells and pilar muscle. In cutaneous neoplasms and other skin diseases, a heterogeneous pattern (0–4+) of PBR expression at lower intensity was seen depending on tumour type and degree of differentiation. PBR expression was greatest in well-differentiated tumours, synonymous with the PBR expression gradient seen in normal skin; and least in poorly differentiated and infiltrative tumour types. Conclusions The haem biosynthetic pathway has been harnessed for PDT of skin carcinomas by application of exogenous aminolaevulinic acid to generate the endogenous photosensitizer protoporphyrin IX (PpIX). Owing to the role of PBR as a transporter of haem precursors in haem synthesis, PBR density and distribution in skin cancers could be a predictor of the capacity for PpIX production and subsequent response to PDT in skin cancers.
Abstract 17228: Rassf1A Inhibits Akt Activation in Cardiac Fibroblasts and Protects Against Ischemia Reperfusion Injury in the Heart
Authors: Dominic Del Re, Peiyong Zhai, Junichi Sadoshima
Journal: Circulation (2011)

Our previous work demonstrated Rassf1A to be a critical mediator of Mst1 activation, the chief component of the mammalian Hippo pathway, in heart failure. In the setting of ischemia/reperfusion (I/R) injury, Mst1 is robustly activated and promotes injury in the heart; however, its regulation remains unclear. Using genetically modified mice in which expression of Rassf1A is altered in a cell type-specific manner, we demonstrate that systemic deletion of rassf1a -/- (KO) does not alter infarct size (36±4% vs 33±3%) or cardiac myocyte apoptosis (1.7±0.2% vs 2.1±0.4%) following I/R versus WT. Conversely, mice harboring deletion of rassf1a in cardiac myocytes ( rassf1a flox/flox αMHC-Cre, CKO) have smaller infarcts (23±2 vs 38±3%, p&lt;0.05) and less apoptosis (0.9±0.2 vs 2.0±0.2%, p&lt;0.05) after I/R. Importantly, attenuation of Mst1 activation in ventricular homogenates was observed in both deletion models, implicating Rassf1A as a positive regulator of Mst1 during I/R. Langendorff global I/R injury yielded similar results - no protection in KO, yet significant protection in CKO hearts versus control mice, suggesting that native cardiac cells are sufficient to mediate this response. Using isolated cardiac fibroblast cultures we determined that Rassf1A negatively regulates activation of Akt in response to oxidative stress. Further, knockdown of endogenous Rassf1A causes increased NF-κB activity, a response mediated by Akt. A candidate molecule screen found exaggerated TNF-α expression in non-myocytes of KO hearts compared to WT (4.8±0.7fold, p&lt;0.05), whereas TNF-α expression was attenuated in CKO hearts (reduced 65±8% vs control, p&lt;0.05). Finally, WT and KO mice were administered TNF-α neutralizing antibody or control IgG and subjected to I/R. KO hearts treated with TNF-α Ab, but not IgG, had reduced infarcts (19±4% vs 34±5%, p&lt;0.05), but no significant reduction in infarct size was observed in WT mice given TNF-α Ab. Taken together these data suggest that TNF-α blockade prevents the deleterious consequences of Rassf1A deletion in non-myocytes while unmasking the protective effect of Rassf1A deletion in cardiac myocytes following I/R. Further, these results demonstrate the importance of non-myocytes in modulating cardiac myocyte survival and I/R injury
Physiology in the French Metropolis
Authors: Wm. Stirling
Journal: BMJ (1896)

THE French capital is unique in respect of the institutions in whichl physiology is tauglht and studied; these institutions differ botlh in their aims anid methods.In the Sorbonne, named after Robert de Sorbolan, of Cambrai (born 1201) phly- siology is tauglht to students of science.Wlhen Paul Bert was professor of physiology, and also up to the present year, the physiological laboratory was not situate withinl the old and classic walls of the anicient Sorbonne, but in the Rue d'Ulm.The Freilch Government has within the last few years greatly extended the Sorbonne, and built palatial laboratories for the several professors of the natural and ex- perimental sciences, including physiology, for Professor
Preemployment Low-Back X-ray Films-Reply
Authors: J. W. Mitchell
Journal: JAMA (1982)

<h3>In Reply.—</h3> The American Occupational Medical Association Committee on Occupational Medical Practice appreciates the comments by Dr Small concerning preplacement lumbosacral spine x-radiation. Without a doubt, the committee does appreciate his concern and totally agrees with the concept of avoiding routine lumbosacral spine preplacement roentgenograms. This was implied in the article as written previously. The committee does believe that preplacement lumbosacral spine x-ray films should be done only in a selective manner based on responsible medical judgment and factors in the medical examination. The possibility of early unknown pregnancy and the less-than-ideal methods available to shield the ovaries properly should make the use of a preplacement lumbosacral spine x-ray film a rare event in women, and then it should be based only on a definite, clear clinical indication. I believe the committee answer did respond to the specific question, which related to certain spinal column defects. We did not editorialize
Culture change is not easy but not that difficult
Authors: N. Toff
Journal: BMJ (2013)

Organisational culture is expressed in shared expectations of which attitudes and behaviours are desirable, acceptable, or tolerable. If standards and expectations are high, we strive to do better; if not, we may bend or change. Unclear, unrealistic, or conflicting demands may result in fear, uncertainty, and erratic outcomes.

Hudson describes how a safety management system was a necessary first …
Heterogeneity of ATP receptors in aortic endothelial cells. Involvement of P2y and P2u receptors in inositol phosphate response.
Authors: S Motte, S Pirotton, J M Boeynaems
Journal: Circulation Research (1993)

Extracellular ATP plays an important role in the regulation of prostacyclin and nitric oxide release from vascular endothelial cells. These cellular responses to ATP are generally attributed to the stimulation of the P2y subtype of P2 purinergic receptors. However, it has recently been suggested that two types of ATP receptors might coexist on endothelial cells. To evaluate this hypothesis, we examined the effects of P2y receptor agonists 2-methylthioadenosine 5'-triphosphate (2MeSATP) and 2'- and 3'-O-(4-benzoylbenzoyl)adenosine 5'-triphosphate (BzATP) and of UTP on the accumulation of inositol phosphates in bovine aortic endothelial cells. BzATP, 2MeSATP, and UTP produced a smaller maximal effect than ATP. The effects of 2MeSATP and UTP were additive, whereas the effects of ATP and either UTP or 2MeSATP were not. Prior exposure to UTP reduced the subsequent response to UTP to 12% of the control response, whereas the response to 2MeSATP was decreased to 61%. Reciprocally, preincubation with 2MeSATP reduced the subsequent response to 2MeSATP to 23% of the control response, whereas the response to UTP was reduced to 73%. Pertussis toxin pretreatment decreased the response to both ATP and UTP (65% and 70% inhibition, respectively), whereas the response to 2MeSATP was not modified. Our data support the hypothesis that two classes of receptors recognizing ATP are expressed on bovine aortic endothelial cells.
801. Fas Knockdown Mediated by siRNA in EBV-Specific Cytotoxic T-Lymphocytes (CTL) Reduces Their Sensitivity to Fas/FasL-Induced Apoptosis
Authors: Gianpietro Dotti, Barbara Savoldo, Martin Pule, Karin C. Straathof, Ettore Biagi, Eric Yvon, Sthephane Vigouroux, Cliona M. Rooney, Malcolm K. Brenner
Journal: Molecular Therapy (2005)

Adoptive immunotherapy with Epstein Barr Virus (EBV) specific CTL has been successfully used to treat patients with EBV related malignancies including Post Transplant Lymphoproliferative disorder, Hodgkin's lymphoma and Nasopharyngeal carcinoma. However, these and other potentially immunogenic tumors have evolved evasion strategies that subvert the effectiveness of the immune response. One such strategy involves expression of FasL, which likely impedes the host immune response by accelerating the apoptotic death of Fas-expressing tumor infiltrating T-cells.
Assisted Circulation by Counterpulsation.
Authors: D. E. Harken
Journal: Annals of Internal Medicine (1963)

s1 April 1963Assisted Circulation by Counterpulsation.D. E. Harken, M.D., A. A. Lefemine, M.D., T. Piemme, M.D., D. K. Brief, M.D., S. Lunzer, M.D.D. E. Harken, M.D.Search for more papers by this author, A. A. Lefemine, M.D.Search for more papers by this author, T. Piemme, M.D.Search for more papers by this author, D. K. Brief, M.D.Search for more papers by this author, S. Lunzer, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-58-4-714_1 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptCounterpulsation permits aspiration of blood during the heart's systole and its return during diastole from a single cannula in the femoral artery. The physiologic effects on the time-tension index, coronary blood flow, myocardial oxygen consumption, shock and coronary artery collaterals will be reviewed. A critical analysis of laboratory and human clinical experience in shock and coronary occlusion will be presented.A controlled series of alternating cases of patients entering the emergency ward in shock from myocardial infarction, unresponsive to therapy in an hour, with and without counterpulsation, will be discussed.The relation of arterio-arterial counterpulsation to other types of circulatory... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Boston, Mass. (CS) PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 April 1963Volume 58, Issue 4Page: 714-714KeywordsCoronary arteriesDiastoleEmergency departmentFemoral arteriesHeartMyocardial infarctionOxygen consumptionResearch laboratoriesShockSystole Issue Published: 1 April 1963 PDF DownloadLoading ...
Physicians' Autonomy -- The Relation between Public and Professional Expectations
Authors: David M. Mirvis
Journal: New England Journal of Medicine (1993)

The practice of medicine has come under increasingly intense public examination during the past several years. Two reasons for this scrutiny are rapidly rising health care costs and the increasing proportion of the population with limited access to health care1. Health care expenditures in the United States exceed those in any other nation, and more than 37 million citizens are not covered by basic health insurance.The public scrutiny has been facilitated by other developments in health care. First, many nonmedical groups, including economists, political scientists, and sociologists, have begun to study health care from their own perspectives and . . .
Aspartate Aminotransferase and Alanine Aminotransferase Levels in Hemodialysis Patients With Positive Hepatitis B/Hepatitis C Serology: Are They Good Predictors of Liver Injury?
Authors: Shitij Arora, Mohammed Siddiqui, Mohammed Ali, Yousif Barzani, Saima Ali, Karishma Kitchloo, Prachi Aggarwal, Premila Bhatt, Rekha Bhandari, Atul Maini, Frantz Duffoo, Vijaypal Arya
Journal: Clinical Gastroenterology and Hepatology (2011)
Epidemiology of systolic and diastolic dysfunction heart failure in 3,471 urban patients
Authors: Akshay K. Khandelwal, John E. McKinnon, Heather J. Shenkman, Vijayamalini Pampati, David Nori, Scott Kaatz, Keisha R. Sandberg, Peter A. McCullough
Journal: Journal of the American College of Cardiology (2002)
Animal Welfare, Ethics, and Legality
Authors: LEO UZYCH
Journal: JNCI Journal of the National Cancer Institute (1990)

Journal Article Animal Welfare, Ethics, and Legality Get access LEO UZYCH LEO UZYCH Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 82, Issue 1, 3 January 1990, Pages 66–68, https://doi.org/10.1093/jnci/82.1.66-a Published: 03 January 1990
Methods for injury surveillance in international cricket
Authors: J W Orchard, D Newman, R Stretch, W Frost, A Mansingh, A Leipus
Journal: British Journal of Sports Medicine (2005)

The varying methods of cricket injury surveillance have made direct comparison of published studies in this field impossible.A consensus regarding definitions and methods to calculate injury rates in cricket was sought between researchers in this field. This was arrived at through a variety of face to face meetings, email communication, and draft reviews between researchers from six of the major cricket playing nations.It is recommended that a cricket injury is defined as any injury or other medical condition that either (a) prevents a player from being fully available for selection for a major match or (b) during a major match, causes a player to be unable to bat, bowl, or keep wicket when required by either the rules or the team's captain. Recommended definitions for injury incidence (for matches, training sessions, and seasons) and injury prevalence are also provided. It is proposed that match injury incidence is calculated using a denominator based on a standard time estimated for player exposure in matches, for the purposes of simplicity. This will allow all injury surveillance systems, including those with limited resources, to make calculations according to a standard definition.The consensus statement presented provides a standard which, if followed, allows meaningful comparison of injury surveillance data from different countries and time periods, which will assist in the possible identification of risk factors for injury in cricket.
Epidermal Growth Factor Receptors with Tyrosine Kinase Domain Mutations Exhibit Reduced Cbl Association, Poor Ubiquitylation, and Down-regulation but Are Efficiently Internalized
Authors: David Padrón, Mitsuo Sato, Jerry W. Shay, Adi F. Gazdar, John D. Minna, Michael G. Roth
Journal: Cancer Research (2007)

Abstract Some non–small cell lung cancers (NSCLC) with epidermal growth factor receptor (EGFR) tyrosine kinase domain mutations require altered signaling through the EGFR for cell survival and are exquisitely sensitive to tyrosine kinase inhibitors. EGFR down-regulation was impaired in two NSCLCs with EGFR tyrosine kinase domain mutations. The mutant receptors were poorly ubiquitylated and exhibited decreased association with the ubiquitin ligase Cbl. Overexpression of Cbl increased the degradation of EGFR. Treatment with geldanamycin, an inhibitor of the chaperone heat shock protein 90, also increased both wild-type and mutant EGFR degradation without affecting internalization. The down-regulation of the mutant EGFRs was still impaired when they were stably expressed in normal human bronchial epithelial cells. Thus, the mutations that altered signaling also decreased the interaction of EGFRs with the mechanisms responsible for endosomal sorting. [Cancer Res 2007;67(16):7695–702]
Pigmented spindle cell naevus and its variants: distinction from melanoma
Authors: R.L. BARNHILL, M.C. MIHM
Journal: British Journal of Dermatology (1989)

We report seven examples of pigmented spindle cell naevus (PSCN) and variants, emphasizing their histopathologic differentiation from malignant melanoma (CMM). Confusion with CMM may occur because of upward migration (pagetoid spread) of cells, prominent lateral extension of lentiginous melanocytic hyperplasia, and cytological atypia in spindle cell naevi. However, these proliferations are usually associated with a symmetrical and orderly growth pattern, confinement of the pagetoid spread to the lower epidermis, 'maturation' of the dermal component, and lack of marked cytological atypia.
Vaccination-Associated Relapse of Immune Thrombocytopenia
Authors: John G. Kelton
Journal: JAMA (1981)

Many patients with immune thrombocytopenia require splenectomy to achieve remission. They are therefore at risk for postsplenectomy septicemia and should receive vaccination against<i>Streptococcus pneumoniae</i>. In experiment situations, antigens contained within this vaccine can initiate a polyclonal B-lymphocyte activation and increased production of specific and nonspecific antibodies. In certain animal models, a polyclonal B-lymphocyte stimulatory response can trigger an autoimmune disorder. Two patients with immune thrombocytopenia had relapses of their immune thrombocytopenia after the administration of pneumococcal and influenza vaccines. These observations suggest that patients with a history of immune thrombocytopenia should be monitored after vaccination. (<i>JAMA</i>1981;245:369-371)
Present Concepts of Benign Breast Disease
Authors: Ira T. Nathanson
Journal: New England Journal of Medicine (1946)

ADVANCES in knowledge of factors concerned in mammary development and function have considerably changed concepts of breast disease in human patients. Through information resulting from systematic surveys, histories, examinations and experimental studies, a new approach to the problem has become available. Since it was demonstrated that hormones were involved in the physiologic response of the breast, it became obvious that they might be of major importance in the genesis of diseases of the mammary gland. Thus, a comprehension of the histology and physiology of the gland is essential to a better understanding of factors that are of possible significance in . . .