tbuckley/cabot-search huggingface dataset:
Comparison of Bio-Plex assays to immunohistochemistry (IHC) for measuring phosphorylated proteins in an in vitro and in vivo model of lung cancer
Authors: Kathleen Rogers, Katherine Crosby, Jeremy Fisher, Michael Lewis, Bradley Smith, Reginaldo Prioli
Journal: Cancer Research (2007)

2820   Protein phosphorylation is a regulatory mechanism for cell growth, survival, apoptosis and response to extracellular signaling events. Deregulation of these pathways is central to the onset and progression of cancer. Identification of proteomic biomarkers is crucial to the understanding and management of cancer. Therefore there is a great need to develop sensitive, quantifiable and multiplexable assays to measure the phosphorylation state of these proteins. Currently, in the clinical setting IHC is the preferred method for the detection of phosphoproteins in cancerous solid tumor tissues. However, this technique is constrained by limited throughput, limited ability to multiplex, lack of quantification and the need for specialists to interpret the results. An alternative technology is a multiplexable bead-based ELISA, such as the Bio-Plex assay. The objective of this study was to demonstrate substantial equivalence between IHC and Bio-Plex detection of phosphorylated biomarkers in an in vitro and in vivo model of cancer. To demonstrate such equivalency, we used HCC827 cells, a non-small cell lung cancer line (NSCLC). Cells or xenografts in nude mice were treated with gefitinib to determine the capability of IHC or Bio-Plex assays to detect drug affects on the drug target and on downstream signaling. The effect of gefitinib inhibition in vitro and in vivo was measured by determining the degree of phosphorylation of Akt, ERK, S6 ribosomal protein and EGFR by Bio-Plex and IHC. To compare treatment groups, phosphorylation ratios were determined (phosphoprotein value/ total protein value) for each analyte. The AxioVision image analysis program (Zeiss) was used to quantify IHC data. Comparisons of gefitinib-treated and control samples for both the in vitro cell cultures and the in vivo xenografts yielded similar results. Both Bio-Plex and IHC assays detected reduced phosphorylation of ERK, S6 ribosomal protein and EGFR in HCC827 cells or xenografts treated with gefitinib compared to control samples. These results demonstrate that the Bio-Plex assay is substantially equivalent to IHC analysis. In summary, the Bio-Plex assay offers a relatively simple way to quantify multiplexed proteomic biomarkers using small samples volumes from cell lysate or tumor tissue. Based on these results, Bio-Plex is a desirable method for detection of the phosphoprotein status of multiple biomarkers.
Phase II trial of erlotinib in chemotherapy-naive women with advanced pulmonary adenocarcinoma
Authors: D. M. Jackman, L. Cioffredi, N. I. Lindeman, L. K. Morse, J. Lucca, D. Weckstein, M. S. Huberman, T. J. Lynch, B. E. Johnson, P. A. Janne
Journal: Journal of Clinical Oncology (2009)

8065 Background: This single-arm phase II study explored the role of clinical characteristics (female gender, adenocarcinoma histology, no tobacco within 1 year) in selecting pts for 1st-line therapy w/ erlotinib. Available tissue for EGFR mutation analysis was required to assess its impact on outcomes. Methods: Eligible pts were chemotherapy-naïve women, stage IIIB/ IV, PS 0–2, adenocarcinoma, and w/ available tissue for analysis of EGFR mutation status. Pts received erlotinib 150 mg PO daily until disease progression or unacceptable toxicity. Primary endpoint was response rate (RR). Secondary endpoints included toxicity, time to progression (TTP), overall survival (OS), and impact of EGFR genotype on clinical outcomes. Results: From 11/04 - 12/08, 84 pts were treated. Median age 68 (range 34–88); 59 PS 0, 24 PS 1, 1 PS 2; race: 79 white, 3 Asian, 2 black; 16 pts had BAC or predominant BAC features; smoking status: 35 never, 49 former. Tox: Rash (90%; 21% grade 3) and diarrhea (69%; 7% grade 3) were the most common toxicities. 32 pts developed toxicity grade 3+ felt likely related to erlotinib. 2 deaths may be treatment-related (1 DIC, 1 hepatic failure). There were also 3 pts w/ PE's (1 fatal). Efficacy: Response (n=84): 0 CR, 27 PR (RR 32%), 27 SD, 23 PD. 7 pts not evaluable (5 tox, 1 non-progression death, 1 withdrawn consent). Median TTP was 5.6 months (95% CI 4.1–7.4 mos), and median OS was 22.7 months (95% CI 15.8 - 26.0 mos). At the time of analysis, there were 36 deaths, 16 pts on treatment w/o progression, and 5 pts lost to follow-up. Compared to smokers, never-smokers trended toward improved RR (43% vs 22%, p=.06), w/ improved TTP (HR .59; 95%CI .36-.96) but no improvement in OS (HR 1.15, 95%CI .58–2.27). Genotype had a more obvious impact on outcomes: compared w/ 37 known wild-type EGFR, 33 pts w/ known sensitizing mutations had a higher response rate (70% vs 0), and significantly improved hazard ratios for both TTP (.20, 95%CI .11-.36) and OS (.36, 95% CI .18 - .73). Results will be updated and outcomes for rarer mutations will be reported. Conclusions: Clinical characteristics may help select appropriate pts for first-line erlotinib when EGFR mutation status is unavailable. However, when available, EGFR genotype is superior to clinical phenotype in selecting pts for first-line erlotinib. [Table: see text]
Door to NIV time: A tale of three audits over 4 years - Are we getting better?
Authors: Andrew Taylor, Sanaa Ismail, Darshan Pandit, Adam Seccombe
Journal: European Respiratory Journal (2013)

Background   Prolonged type 2 respiratory failure (T2RF) is associated with increased mortality thus delay in starting non-invasive ventilation (NIV) treatment should be minimised. BTS guidelines recommend up to one hour of best medical therapy before considering NIV.   Aims and Objectives   Retrospective audits in 2008 and 2010 at a UK city hospital found delays in NIV initiation. This prompted a proforma for NIV candidates in 2008 and junior doctor training to ensure best medical therapy prior to NIV in 2010. A 2012 audit aimed to investigate the impact of these measures.   Methods   All patients receiving NIV for T2RF from August to October 2012 were reviewed prospectively. Those receiving CPAP or who used home NIV were excluded as per previous audits. Data from the notes were used to calculate time delays along the NIV pathway and gather clinical and demographic variables.   Results   The average time from door to NIV in 2008 was 325 minutes. This improved to 287 minutes in 2010 following the introduction of a proforma. In 2012 this time increased to 340 minutes. Further analysis showed that this increase was in large part due to a reduction in the percentage of patients receiving NIV less than one hour from admission (31.4% in 2010; 10.3% in 2012) suggesting a sufficient trial of maximum medical therapy had been attempted in more cases. Mortality was reduced from 46.7% in 2010 to 24.5% in 2012 with no significant change in the patient characteristics.   Conclusions   The use of a proforma alongside focused training has led to more appropriate NIV use. Our audit highlights the importance of using NIV alongside, not instead of, best medical therapy; the observed fall in mortality a good reflection of improved practices.
Tetralogy of Fallot with Absent Pulmonary Valve
Authors: JEFFREY B. LAKIER, PAUL STANGER, MICHAEL A. HEYMANN, JULIEN I. E. HOFFMAN, ABRAHAM M. RUDOLPH
Journal: Circulation (1974)

Absent or hypoplastic pulmonary valve is an uncommon condition usually associated with a ventricular septal defect and an obstructive pulmonary valve ring. Secondary abnormalities involving the pulmonary arteries and major bronchi are common, and many result in severe pulmonary complications. Eight patients with absent pulmonary valve, ventricular septal defect and obstructed pulmonary valve ring are herein described. The clinical features, cardiac catheterization, cineangiographic and postmortem findings are presented. Possible fetal hemodynamics and their influences are discussed, as are postnatal hemodynamics and their clinical consequences. Patients with this combination of lesions have been regarded as having a very poor prognosis, and recent publications have advocated early surgical intervention; however, most published series are small, and only 106 cases have been documented. These cases have been reviewed for clinical and anatomic features as well as an overview of prognosis and results of surgical intervention.
Abstract 12622: Western Diet for One Month Impairs Myocardial Energetics and Both Systolic and Diastolic Pump Function in the Mouse Heart
Authors: Ivan Luptak, Aaron L Sverdlov, Aly Elezaby, Edward J Miller, David R Pimentel, Marc Liesa, Orian Shirihai, Richard A Cohen, James A Balschi, Wilson S Colucci
Journal: Circulation (2014)

Background and Significance: Metabolic heart disease(MHD) is common in patients with obesity, type 2 diabetes and/or metabolic syndrome. We found cardiac mitochondrial dysfunction in mice with obesity-related MHD due to consumption of a high fat high sucrose (HFHS) diet. The effects of diet-induced obesity on cardiac energetics and pump function in the intact organ are largely unknown. Hypothesis: We tested the hypothesis that cardiac mitochondrial dysfunction due to HFHS diet for one month impairs energetic and contractile reserve in the intact heart. Methods and Results: Mice were fed a HFHS or control diet (CD) for 1 month. In isolated cardiac mitochondria from HFHS-fed mice (vs. CD) the maximal rate of ATP synthesis was decreased for complex I (down by 42%; p&lt;0.05) and II (down by 37%; p&lt;0.05) substrates. We measured myocardial energetics in isolated perfused hearts using 31P NMR spectroscopy at baseline (450 bpm, 2 mM Ca++) and high workload (600 bpm, 4 mM Ca++) in HFHS (n=7) and CD (n=8) hearts. In HFHS-fed hearts, myocardial ATP concentration was the same at baseline (10.5±0.4 vs 10.4±0.5 mM) and high workload (7.4±0.9 vs. 7.5±0.5 mM) as that of CD hearts. However, in HFHS-fed hearts the concentration of phosphocreatine, which reflects energy reserve, was decreased at baseline (13±0.7 vs. 17.5±0.8 mM; p&lt;0.01) and decreased further at high workload (down to 7.3±0.7; p&lt;0.01 vs. baseline and p&lt;0.01 vs. CD at 10.5±0.4 mM) - indicating a mismatch between ATP production and utilization. In HFHS hearts, the diastolic pressure-volume relationship was shifted upward and leftward at baseline, indicative of diastolic dysfunction. In HFHS hearts, baseline systolic function was preserved (rate pressure product 41,600±2,200 vs. 41,000±2,000 mmHg/min), but was decreased at high workload (54,800±7,200 vs. 85,300±4,300 mmHg/min; p&lt;0.01 vs. CD), reflecting an impaired contractile reserve. Conclusion: Consumption of a HFHS diet for one month causes cardiac mitochondrial dysfunction with reduced ATP synthesis leading to impaired energetic reserve in the intact heart. Diastolic dysfunction at rest and the impaired ability to increase systolic function with increased work demands may result from impaired energetics in MHD.
Colon cancer chemopreventive properties of β-Escin, a triterpene saponin constituent of Aesculus hippocastanum
Authors: Jagan M. R. Patlolla, Venkat Swamy Malisetty, Jayadev Raju, Barbara Simi, Chinthalapally V. Rao
Journal: Cancer Research (2005)

2474   Extracts of  Aesculus hippocastanum  (horse chestnut) seed have been used in the treatment of chronic venous insufficiency, edema and hemorrhoids. Most of the medicinal beneficial effects of horse chestnut are attributed to its principal component β-escin or aescin. Recent studies suggest that β-escin may possess anti-inflammatory, anti-hyaluronidase, and anti-histamine properties. We have evaluated the preventive efficacy of dietary β-escin on azoxymethane (AOM)-induced colonic aberrant crypt foci (ACF) and analyzed the tumor cell growth inhibitory effects in the HT-29 human colon cancer cell line. To evaluate inhibitory properties of β-escin on colonic ACF, 7-week-old male F344 rats were fed experimental diets containing 0, 0.025% or 0.05% β-escin. One week later rats received  s.c.  injections of AOM (15 mg/kg body wt., once weekly for 2 weeks) or equal volume of normal saline (vehicle). Rats were continued on experimental diets for 10 weeks and sacrificed. Colons were evaluated histopathologically for ACF and expression levels of markers associated with proliferation and apoptosis. Administration of dietary β-escin significantly suppressed total colonic ACF formation (∼43%, p
Oliver Goldsmith, M.D.
Authors: Louis H. Roddis
Journal: Annals of Internal Medicine (1932)

Article1 May 1932Oliver Goldsmith, M.D.LOUIS H. RODDIS, M.D.LOUIS H. RODDIS, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-5-11-1427 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptWith no other medical poet is the dignified doctoral prefix more commonly employed. He was "Dr. Goldsmith" to Boswell and the Johnson circle, and his contemporaries almost without exception referred to him as the "Doctor" yet the medical side of Goldsmith's life has been rather neglected, though it is both a considerable and interesting subject. The circumstances of his medical education, his attempts to practice in Southwark and in London, his relation to one of the celebrated nostrums of the day, and its use in his last illness are all well attested though not commonly known facts.His biographers are...Bibliography Foster J Life of Oliver Goldsmith, . Google Scholar Irving W Life of Oliver Goldsmith, . Google Scholar Dobson A Life of Oliver Goldsmith, . Google Scholar Black W Life of Oliver Goldsmith, (English Men of Letters). Google Scholar Dobson A "18th Century Vignettes", . Google Scholar Macauley's Essay on Goldsmith. Google Scholar Boswell's Life of Johnson. Google Scholar Hawes and Newberry's statements regarding last illness and death of Oliver Goldsmith. Google Scholar Edition of Goldsmith's poems illustrated by Cope and others. Google Scholar Edition of Goldsmith's complete works. Google Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Medical Corps U. S. Navy*Received for publication, October 12, 1931. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 May 1932Volume 5, Issue 11Page: 1427-1436KeywordsMedical education Issue Published: 1 May 1932 PDF downloadLoading ...
Abstract 2668: RG7116, a novel humanized anti-HER3 antibody with superior preclinical <i>in vitro</i> and <i>in vivo</i> efficacy in combination with, everolimus and other anti-cancer agents
Authors: Birgit Bossenmaier, Thomas Friess, Martin Weisser, Stefanie Lechner, Esther Abraham, Monika Hoch, Christian Mirschberger
Journal: Cancer Research (2014)

Abstract HER3 is a member of the Human Epidermal Growth Factor Receptor (HER) family. HER3 is a kinase dead receptor, but by forming heterodimers with other HER family receptors, HER3 works as amplifier for PI3 kinase driven tumorigenesis. It has been reported that tumors treated with EGFR-, HER2-, cMET-or mTOR targeted therapies can escape via HER3 activation or upregulation. HER3 is expressed in a large variety of tumors for example in non-small cell lung cancer (NSCLC), head and neck, colorectal, gastric, pancreatic, breast, ovarian, thyroid and prostate cancer. Anti-HER3 antibodies can work via various mechanisms including: (1) blocking ligand (HRGs) binding to the receptor, (2) blocking heterodimerization with other HER family members (HER1, 2 and 4), (3) downregulation of the receptor from the cell surface, and (4) engaging immune effector functions such as antibody-dependent cellular cytotoxicity (ADCC). The first three mechanisms lead to inhibition of HER3 phosphorylation and downstream signaling thereby resulting in tumor cell growth inhibition, while ADCC is a mechanism of direct target cell killing triggered by cross-linking of Fc receptors on immune effector cells (e.g. NK cells, macrophages). RG7116 is a novel humanized and glycoengineered IgG1 antibody currently in clinical development, that binds to HER3 with high affinity. This antibody prevents ligand binding and receptor heterodimerization, thereby blocking receptor phosphorylation. In various tumor xenograft models monotherapy treatment with this antibody leads to substantial tumor growth inhibition. Only in a few cases monotherapy treatment resulted in complete tumor remission. Most of the models initially show convincing efficacy, but tumors regrow after a while. Combination therapy with other HER targeted therapies such as pertuzumab, cetuximab or erlotinib, lead to complete remission in preclinical models. The combination of RG7116 with downstream signaling inhibitors like: everolimus (mTOR) andand other anti-cancer agents leads to increased efficacy. Citation Format: Birgit Bossenmaier, Thomas Friess, Martin Weisser, Stefanie Lechner, Esther Abraham, Monika Hoch, Christian Mirschberger. RG7116, a novel humanized anti-HER3 antibody with superior preclinical in vitro and in vivo efficacy in combination with, everolimus and other anti-cancer agents. [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 2668. doi:10.1158/1538-7445.AM2014-2668
Multiple actinic keratoses and squamous cell carcinomas on the sun-exposed areas of widespread vitiligo
Authors: S. Akimoto, Y. Suzuki, O. Ishikawa
Journal: British Journal of Dermatology (2000)

Journal Article Multiple actinic keratoses and squamous cell carcinomas on the sun‐exposed areas of widespread vitiligo Get access S. Akimoto, S. Akimoto The Department of Dermatology, Gunma University School of Medicine, 3‐39‐22 Schowamachi, Maebashi, Gunma 371‐8511, Japan E‐mail: sakimoto@akagi.sb.gunma‐u.ac.jp Search for other works by this author on: Oxford Academic Google Scholar Y. Suzuki, Y. Suzuki The Department of Dermatology, Gunma University School of Medicine, 3‐39‐22 Schowamachi, Maebashi, Gunma 371‐8511, Japan E‐mail: sakimoto@akagi.sb.gunma‐u.ac.jp Search for other works by this author on: Oxford Academic Google Scholar O. Ishikawa O. Ishikawa The Department of Dermatology, Gunma University School of Medicine, 3‐39‐22 Schowamachi, Maebashi, Gunma 371‐8511, Japan E‐mail: sakimoto@akagi.sb.gunma‐u.ac.jp Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 142, Issue 4, 1 April 2000, Pages 824–825, https://doi.org/10.1046/j.1365-2133.2000.03440.x Published: 01 April 2000
Abstract 180: Myocyte-Specific Excision of the Murine Vinculin Gene Leads to Arrhythmias, Sudden Death and Heart Failure due to Dissolution of the Intercalated Disc Structure
Authors: Alice E Zemljic-Harpf, Joel C Miller, Scott A Henderson, Ana M Manso, Nancy D Dalton, Andrea K Thor, Guy A Perkins, Robert S Ross
Journal: Circulation (2006)
Glucocorticoid resorption and effects on the hypothalamic-pituitary adrenal axis after intra-articular treatment of the knee in mobile and resting patients
Authors: Tomas Weitoft, Lars Rönnblom
Journal: Annals of the Rheumatic Diseases (2005)

Glucocorticoid resorption and effects on the hypothalamic-pituitary adrenal axis after intra-articular treatment of the knee in mobile and resting patients
Racial Differences in Coronary Vasomotor Response or Selection Bias?
Authors: F. Javier Nieto
Journal: Circulation (2001)

To the Editor:Pristipino et al 1 found that, compared with white patients in Italy, Japanese patients with myocardial infarction had a 3-fold-greater incidence of coronary spasm and a vasoconstrictive response to acetylcholine.The authors conclude that these "major racial differences in the coronary constrictor responseѧwarrant further investigations because they may have relevant pathophysiological and therapeutic implications."In my opinion, interpreting these differences as "racial" can be problematic, particularly in view of the possibility of selection bias stemming from the different risk profile of the study groups.Japanese patients in this study were much older than the white patients (mean age, 68.8 versus 54.8 years) and had much lower mean serum cholesterol levels (183 versus 247 mg/dL), serum triglyceride levels (87 versus 209 mg/dL), and body mass indexes (22.1 versus 26.5 kg/m 2 ).These dramatic differences cast serious doubts on the comparability of the underlying disease process in the 2 groups.Atherosclerotic disease is an extremely complex multifactorial process in which many metabolic and physical factors come into play.Furthermore, the old Virchowian hypothesis of the role of inflammation in this process has been recently resurrected. 2ompared with Western countries, coronary heart disease (CHD) is very uncommon in Japan.According to 1998 World Health Organization data, 3 CHD mortality rates among men 35-74 years old are 5.7% in Japan, 15% in Italy, and 21.4% in the United States.This low CHD risk is consistent with the low cholesterol and low body weight of the Japanese population, and the Japanese patients in Pristipino et al's study 1 fit this general profile.Why then did these patients have a myocardial infarction?Why do they have angiographic features similar to their white counterparts despite their much lower lipid levels?Could it be that, among all the constellation of risk factors involved, the predominant factors that caused the underlying atherosclerosis disease in these Japanese patients are different than those in the white patients?For example, hyperlipidemia may play a secondary role, and inflammation, endothelial dysfunction, or other factors (eg, infection?) 4 may be the predominant players.In other words, these 2 groups of patients may suffer from a different form of atherosclerosis, even if it looks similar in the angiogram.Before concluding that the observed differences are racial, patients who have similar profiles with regard to the major CHD risk factors will need to be compared.For example, how will the vasomotor response of Japanese patients compare with that among lean whites with low cholesterol levels who experience a myocardial infarction?