tbuckley/cabot-search huggingface dataset:
Abstract 4966: Influence of the microenvironment on drug sensitivity in breast cancer using a three-dimensional cell culture model.
Authors: Carrie J. Lovitt, Vicky M. Avery
Journal: Cancer Research (2013)

Abstract Three-dimensional (3D) cell culture is an important research tool and an invaluable alternative to two-dimensional (2D) cell culture as it is more suitable to represent in vivo conditions. The tumor microenvironment influences cellular activity and using 3D cell culture allows these interactions to be studied in vitro. We have evaluated the efficacy of a novel 3D cell culture model for breast cancer and determined cellular responses caused by drug activity. We have recently developed and optimized a miniaturized 3D breast cancer culture model. Our model uses reconstituted basement membrane from Growth Factor Reduced Matrigel™ as a scaffold and is suitable for semi-automated early stage drug discovery. The newly developed 3D culture model has been extensively characterized for reproducibility and the activity of known anti-breast cancer therapies. Notably, anthracyclines and taxanes showed significantly altered drug sensitivity in 3D when compared to monolayer cell cultures of breast cancer cell lines. To determine the mechanisms underlying the altered sensitivity in 3D cell culture, we sought to identify the differences between untreated and drug treated spheroids, as well as the differences between 2D and 3D cell culture responses to anthracyclines and taxanes. We evaluated proliferation, penetration, cellular architecture and signaling of major cellular pathways in our 3D model. We will discuss the proliferation rate comparing 2D and 3D cell culture models and drug penetration (exemplified by doxorubicin) in 3D cell culture. The effect of anthracyclines and taxanes on the 3D cellular architecture, without the influence of extracellular matrix proteins in the microenvironment, will also be presented. In addition, we have characterized the signaling pathways in 2D and 3D cell culture commonly associated with enhanced drug resistance and other relevant proteins including those associated with apoptosis. Deconstructing the cellular processes in 3D breast cancer cell culture in response to breast cancer therapies has the potential to elucidate drug resistance mechanisms. The results obtained from this research illustrate the characteristics and mechanisms of both monolayer and 3D cell culture with respect to anthracycline and taxane drug activity. These results demonstrate the benefits of 3D cell culture in early stage novel compound evaluation for breast cancer. Citation Format: Carrie J. Lovitt, Vicky M. Avery. Influence of the microenvironment on drug sensitivity in breast cancer using a three-dimensional cell culture model. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4966. doi:10.1158/1538-7445.AM2013-4966
61 TREATMENT WITH SOFOSBUVIR + RIBAVIRIN FOR 12 WEEKS ACHIEVES SVR12 OF 78% IN GT2/3 INTERFERON-INELIGIBLE, -INTOLERANT, OR -UNWILLING PATIENTS: RESULTS OF THE PHASE 3 POSITRON TRIAL
Authors: I. Jacobson, E.M. Yoshida, M. Sulkowski, D.R. Nelson, E. Svarovskaia, D. An, J. McNally, D.M. Brainard, W.T. Symonds, J.G. McHutchison, S. Pianko, K.V. Kowdley
Journal: Journal of Hepatology (2013)
THE NECESSITY FOR CONSTRUCTING ANOTHER HOSPITAL FOR THE INSANE IN ILLINOIS.
Authors: BOERNE BETTMAN
Journal: JAMA (1896)

The need of another insane hospital must be evident to any one who has beheld the poor accommodations accorded to the insane detained in the county poorhouses. The best authorities the world over are unanimous in their opinion regarding the necessity of State care for these defective individuals. The four institutions which now exist accommodate 5,000 patients, fully 2,000 more are scattered throughout the State and should, in our judgment, find lodgment in State buildings thoroughly equipped for their care and treatment. For further particulars regarding the construction of building and the most advanced methods for the care and treatment of the patients and other matters relating to the subject of insanity, we refer to the excellent reports prepared at the suggestion of Governor Altgeld by the superintendent and medical staff of the State lunatic asylums. They have appeared in print under the heading, "Compilation of Special Reports of Superintendents
Manpower and hours of work agreements are complementary.
Authors: P D Miller
Journal: BMJ (1991)

Other causes of digital gangrene Severe Raynaud's phenomenon can result in ulceration of the finger tips.Digital ulceration or gangrene may also be caused by non-vasospastic conditions.Emboli may be discharged from the fibrillating atrium, the ventricle after a myocardial infarction, or from an aneurysm of thhe subclavian artery.Arteriovenous malformations in the hand can cause enough shunting of blood to result in distal ischaemia.Occasionally, thrombotic disorders such as polycythaemia or thrombocythaemia may cause digital ischaemia, but this is most unusual in the hand.Vascutherm gloves are distributed by Camp Ltd,Worcester.
The experimental use of antisense oligonucleotides: a guide for the perplexed
Authors: C.A. Stein
Journal: Journal of Clinical Investigation (2001)

Antisense oligonucleotide biotechnology, at least in theory, provides a specific, rapid, and potentially high-throughput method for inhibiting gene expression and exploring gene function. Over the past decade, a plethora of experiments has been submitted, and a lesser number published, employing this approach to inhibiting gene expression at the mRNA level. The specificity of the antisense approach stems, of course, from the specificity (or, the “information content”) of the Watson-Crick base pair interaction.

The fact that antisense oligonucleotides carry significant information in addition to that denoted by their nucleotide sequences is frequently overlooked. This oversight has frequently led to the lack of rigorous controls for many antisense experiments, and, on all too many occasions, to the inappropriate interpretation of experimental data (1). Indeed, serious questions have arisen as to whether an observed biological effect in an antisense experiment has indeed been produced by an antisense mechanism, or whether it is due to a complex combination of non–sequence specific effects. Investigators must therefore understand how to employ antisense technology properly and should recognize its limitations.
Prostaglandin synthase-mediated metabolism of carcinogens and a potential role for peroxyl radicals as reactive intermediates.
Authors: L J Marnett
Journal: Environmental Health Perspectives (1990)

Prostaglandin-H synthase is unique among enzymes of the plant and animal kingdom in its ability to biosynthesize and metabolize hydroperoxides. Its cyclooxygenase activity oxygenates polyunsaturated fatty acids to hydroperoxy endoperoxides, and its peroxidase activity reduces the hydroperoxy group to hydroxy groups. Higher oxidation states of the peroxidase oxidize reducing substrates to electron-deficient derivatives that react with macromolecular nucleophiles. In the case of aromatic amines, the electron-deficient derivatives are mutagenic to bacterial and mammalian cells. beta-Dicarbonyl compounds and retinoic acid are oxidized to carbon-centered radicals that react with O2 to form peroxyl free radicals. Peroxyl radicals are the most stable oxy radicals and are able to diffuse some distance from the site of their generation. Peroxyl radicals are also formed during lipid peroxidation and in the reaction of polyunsaturated fatty acid hydroperoxides with metal complexes and metalloproteins. Peroxyl radicals epoxidize isolated doubled bonds of compounds such as 7,8-dihydroxy-7,8-dihydrobenzo(a)pyrene (BP-7,8-diol); 3,4-dihydroxy-3,4-dihydrobenzo(a)anthracene; and aflatoxin B1. The epoxide products represent the ultimate carcinogenic forms of the respective compounds. Techniques for quantitating the extent of peroxidase dependent or peroxyl radical-dependent metabolism in vivo make use of differences in the structure or stereochemistry of reactive intermediates formed by peroxidases relative to cytochromes P-450. Differences in the relative amounts of hydrolysis products and DNA adducts derived from anti- and syn-dihydrodiolepoxides following application of BP-7,8-diol to mouse skin in vivo indicate peroxyl radicals play a significant role in metabolism of BP-7,8-diol in uninduced animals.
A pilot project examining the predicted preferences of patients and physicians in the primary prophylaxis of variceal hemorrhage
Authors: Anna V. Longacre, Avlin Imaeda, Guadalupe Garcia-Tsao, Liana Fraenkel
Journal: Hepatology (2007)

Endoscopic variceal ligation (EVL) and nonselective beta-blockers (hereafter just called beta-blockers) are both effective for primary prophylaxis for variceal hemorrhage; however, the route of administration and side effects of these treatments are distinct. The objective of this study was to examine predicted preferences of patients and physicians for the primary prevention of variceal hemorrhage. Untreated patients with newly diagnosed esophageal varices and practicing gastroenterologists were enrolled in this study. Patients with contraindications to either EVL or beta-blockers were excluded. Predicted preferences for treatment were evaluated with an interactive computer task designed to elicit subjects' trade-offs related to the route of administration, risk of fatigue, sexual dysfunction, dysphagia, shortness of breath and/or hypotension, procedure-related bleeding, and perforation. Fifty-three patients and 61 physicians were enrolled. Thirty-four (64%) patients and 35 (57%) physicians preferred EVL over beta-blockers. Patients' predicted preferences were most strongly influenced by the risks of shortness of breath or hypotension, fatigue, and procedure-related bleeding, whereas physicians placed greater importance on procedure-related bleeding, sexual dysfunction, and perforation. Forty-eight patients were prescribed beta-blockers, two were not given prophylaxis, and three were lost to follow-up. Conclusion: Predicted treatment preferences among both patients and physicians for primary prophylaxis of variceal hemorrhage vary significantly. Physicians in this study preferring EVL stated that they prescribe beta-blockers as first-line therapy in order to remain compliant with guidelines. Physicians should discuss both EVL and beta-blockers with patients requiring primary prophylaxis for variceal hemorrhage. Future guidelines should incorporate individual patient preferences. (Hepatology 2007.)
Analysis of mouse LMIR5/CLM-7 as an activating receptor: differential regulation of LMIR5/CLM-7 in mouse versus human cells
Authors: Yoshinori Yamanishi, Jiro Kitaura, Kumi Izawa, Takayuki Matsuoka, Toshihiko Oki, Yang Lu, Fumi Shibata, Satoshi Yamazaki, Hidetoshi Kumagai, Hideaki Nakajima, Mari Maeda-Yamamoto, Victor L. J. Tybulewicz, Toshiyuki Takai, Toshio Kitamura
Journal: Blood (2007)
Individualizing Aspirin Therapy for Prevention of Cardiovascular Events
Authors: Jean-Pierre Boissel
Journal: JAMA (1998)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Postnatal depression: does no one care?
Authors: J Garrigan
Journal: BMJ (1980)

SIR,-With reference to the article "Postnatal depression: does no one care ?" (8 December, p 1487), I would like to point out that the subject of postpartum psychiatric disorders has been scrutinised and been the subject of a lot of time and energy of many researchers for over a century.'Needless to say, numerous papers and research projects have been published during this time.These concern many aspects of the whole spectrum of these disorders-from acute psychotic disorders2 to the "three-day blues syndrome,"'3 including postpartum depression.4With this history in mind I would like to reassure the author that the lack of "appropriate hormones" to treat people like his wife is not the result of people "not having a care" to answer the queries he poses but is much more likely to be a direct reflection of the complexity of the biochemical and endo- crinological state of the psychiatrically ill puerperal women.As far as the "lack of warning" that patients will be affected is concerned, epidemiological studies and research into the aetiology of these disorders are plentiful5 7 and concern in this respect is in an ever-evolving state.
Economic consequences of postinfarction prophylaxis with beta blockers: cost effectiveness of metoprolol.
Authors: G Olsson, L A Levin, N Rehnqvist
Journal: BMJ (1987)

Treatment with certain beta adrenoceptor blocking agents after myocardial infarction reduces mortality and the incidence of reinfarction. Data from a randomised placebo controlled study of the beta 1 selective blocker metoprolol given as secondary prophylaxis were therefore analysed for the possible cost effectiveness of extending this treatment to the general population of patients with myocardial infarction. Metoprolol 100 mg twice daily and matching placebo were given to 154 and 147 patients, respectively, for three years. During this period drug costs for the beta blocker, digitalis, and diuretics were analysed as well as costs of readmission for cardiac problems and indirect costs arising from sick leave or early retirement. Active treatment with metoprolol significantly reduced costs of readmission as well as indirect costs. The net effect per patient over the three years was a reduction of roughly kr 19,000 (1930 pounds). These results suggest that beta blocker treatment given as secondary prophylaxis after myocardial infarction is highly cost effective.
Institutional Differences in Postoperative Death Rates
Authors: Lincoln E. Moses
Journal: JAMA (1968)

The National Halothane Study was designed to examine the possible association of halothane anesthesia and postoperative massive hepatic necrosis. It was a retrospective survey of the incidence of fatal massive hepatic necrosis and overall death rate following general anesthesia in 34 hospitals for the four-year period from 1959 through 1962. A summary of the observed incidences of liver necrosis and mortality following halothane anesthesia and following use of other general anesthetic agents has been published inThe Journal.<sup>1</sup>One important by-product of the study was the finding of large differences in postoperative mortality occurring among the participating institutions. The following communication represents a summary of the statistical analysis of these institutional differences and a discussion of their possible significance. Death rates for the six-week period following surgery varied widely among the 34 institutions cooperating in this study. These death rates ranged from 0.27% to 6.40%, a 24-fold ratio. In
IMPROVED NEUROCOGNITIVE OUTCOME AFTER CORONARY ARTERY BYPASS SURGERY USING MINIMAL VERSUS CONVENTIONAL EXTRACORPOREAL CIRCULATION: A RANDOMIZED CONTROLLED STUDY
Authors: Polychronis Antonitsis, Kyriakos Anastasiadis, Helena Argiriadou, Mary H. Kosmidis, Kalliopi Megari, Evanthia Thomaidou, Eleni Aretouli, Christos Papakonstantinou
Journal: Journal of the American College of Cardiology (2011)
Arbitration of medical liability
Authors: R. Bergen
Journal: JAMA (1970)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
The Normal Hematocrit Study — Follow-up
Authors: Anatole Besarab, David A. Goodkin, Allen R. Nissenson
Journal: New England Journal of Medicine (2008)

clinical benefit -continue to prevent the practical application of this strategy in the United States.These include limited funding and infrastructure within EMS systems in general, as well as concerns about legal liability and reimbursement. 4 In addition, EMS systems with enough volume to justify dedicating resources to overcome these barriers are likely to be in urban areas where there is the potential for rapid access to primary PCI. 5
Cytokines in the bronchoalveolar lavage fluid of patients with active pulmonary sarcoidosis.
Authors: R E Girgis, M A Basha, M Maliarik, J Popovich, M C Iannuzzi
Journal: American Journal of Respiratory and Critical Care Medicine (1995)

Numerous cytokines are thought to be important in the pathogenesis of granulomatous inflammation and subsequent fibrosis in sarcoidosis. Interleukin (IL)-6 and IL-8, two recently described cytokines with a broad spectrum of proinflammatory effects, could participate in this disease. We obtained bronchoalveolar lavage fluid (BALF) from 16 subjects (13 African-American, three Caucasian) with untreated active pulmonary sarcoidosis and 10 healthy nonsmoking volunteers (nine Caucasian, one African-American). Concentrated BALF was analyzed by an ELISA for IL-6, IL-8, and albumin. The median IL-6 level was 9.8 pg/mg albumin (range, 0-278) for the sarcoid group compared with 0.14 pg/mg (range, 0.14-9.8) in the control subjects (p = 0.001). The corresponding values for IL-8 were 202 pg/mg (range, 35-2179) versus 5.0 pg/mg (range, 0-44) in the control subjects (p < 0.001). Among the sarcoid patients, BALF IL-6 and IL-8 levels correlated with each other (r = 0.96, p < 0.001), and both cytokines correlated with the BALF neutrophil percentage (r = 0.96 and 0.95, respectively; p < 0.001 for both). No difference was detected in IL-8 concentrations as measured by ELISA in culture supernatants of alveolar macrophages obtained from five sarcoid patients and five control subjects. We conclude that IL-6 and IL-8 are elevated in BALF of patients with active sarcoidosis and may be important modulators of the disease process.
Pancreatic growth: interaction of exogenous cholecystokinin, a protease inhibitor, and a cholecystokinin receptor antagonist in mice.
Authors: C Niederau, R A Liddle, J A Williams, J H Grendell
Journal: Gut (1987)

The effects on pancreatic growth and plasma CCK concentration of chronic feeding of camostate (400 mg/kg day for 10 days), a potent inhibitor of serine proteases including trypsin, were assessed in the mouse. For comparison, the trophic effects of chronic exogenous administration of CCK octapeptide (sc injection of 1 microgram/kg day every eight hours for 10 days) were also studied. In addition, the effects of a proglumide-analogue CCK-receptor antagonist (CR1409) on the stimulatory actions of camostate feeding and chronic administration of exogenous CCK were studied. The effects of the combination of chronic camostate feeding and sc injections of CCK, the effects of acute camostate feeding, and the effects of the CCK-receptor antagonist given without camostate or CCK were also studied. The results show that chronic camostate feeding markedly increased CCK plasma concentrations eight-fold over control values, and that acute camostate feeding increased plasma concentration to four fold of control values. Correspondingly, chronic camostate feeding markedly increased pancreatic weight, protein and DNA content. Exogenous CCK-8 also had qualitatively similar, but quantitatively less potent stimulatory effects. The combination of camostate and CCK-8 resulted in an additive stimulatory effect. The trophic actions of exogenous and endogenous CCK grossly increased chymotrypsinogen content, but left amylase content unaffected. The CCK-receptor antagonist CR 1409 completely abolished the trophic effects of exogenous CCK and greatly inhibited the effects of chronic camostate feeding. The CCK antagonist decreased pancreatic weight, DNA and protein content compared to control values when given without any CCK or camostate. We conclude that the protease inhibitor camostate is a very strong release effector of CCK and exerts a powerful trophic effect on mouse pancreas which is probably mediated by CCK. Furthermore, physiological increases of CCK during feeding of regular chow appear to exert trophic effects on the exocrine pancreas.
Cold agglutinin induced autoimmune hemolytic anemia and NK‐cell leukemia—A new association
Authors: Amy Skorupa, Uzair B. Chaudhary, John Lazarchick
Journal: American Journal of Hematology (2007)

Abstract Cold agglutinin induced autoimmune hemolytic anemia is uncommonly associated with leukemia and lymphomas. We present a case of a young Mexican female presenting with a cold agglutinin hemolytic anemia with expression of a rare Pr antigen specificity and an aggressive NK‐cell leukemia. Our patient had a rapid fatal course. To our knowledge this is the first reported case of such an association. Am. J. Hematol., 2007. © 2007 Wiley‐Liss, Inc.
Tuberculosis and anti-TNF- treatment
Authors: L P Ormerod
Journal: Thorax (2004)

New evidence-based guidance on anti-TNF-α treatment is being developed by the Joint Tuberculosis Committee of the BTS in conjunction with the British Societies of Rheumatology and Gastroenterology

Anti-tumour necrosis factor (TNF) treatment for rheumatoid arthritis and Crohn’s disease has been introduced over the last few years. Infliximab (Remicade; Schering-Plough), a humanised monoclonal antibody, is licensed for the treatment of both rheumatoid arthritis1 and Crohn’s disease,2 while etanercept (Enbrel; Wyeth Laboratories), a fusion protein binding free TNF-α using the soluble portion of the TNFR-2 receptor,3 and adalimumab (Humira; Abbott Laboratories), a fully humanised monoclonal antibody,4 are licensed for treating rheumatoid arthritis. Post-marketing surveillance in the USA5 has identified cases of tuberculosis (TB) associated with infliximab use and a smaller number with etanercept. TB cases have also been reported in association with adalimumab (Humira prescribing information, Abbott Laboratories, 2002). The cases …