Translational Lessons Research Articles

Lung Adenocarcinoma: Lessons in Translation from Bench to Bedside

Lung cancer is currently the leading cause of cancer-related death in the United States and worldwide, accounting for approximately a third of all cancer diagnoses and deaths. The American Cancer Society estimates 159,390 deaths from lung cancer in the United States for 2009 alone. The high mortality rate associated with lung cancer has prompted numerous exhaustive efforts to identify novel therapeutic targets and treatment modalities for this deadly disease. The characterization of signaling pathways underlying the development and progression of lung cancer, particularly lung adenocarcinoma, has been instrumental in developing novel therapeutic strategies to target aggressive metastatic disease. This paradigm is best illustrated in lung adenocarcinoma by recent studies of the epidermal growth factor receptor, which has been identified to be a critical diagnostic and therapeutic target. Our understanding of the central role of epidermal growth factor receptor in the development and progression of lung adenocarcinoma has led to the development of molecular agents against this key oncogene that have demonstrated significant clinical efficacy against the disease. Despite these successes, de novo or acquired resistance to these anti-epidermal growth factor receptor agents invariably develops, either through additional mutations in the epidermal growth factor receptor, or abnormal regulation of downstream signaling pathways. Thus, it is necessary to further investigate the molecular determinants of treatment resistance and to develop novel therapeutic strategies directed specifically against the molecular drivers of metastatic chemoresistant lung cancer. Given the heterogeneity and convergence of signaling pathways underlying both disease etiology and chemoresistance, future efforts to administer rationally designed agents against multiple molecular targets could serve to improve both first-line and second-line therapies for patients with lung adenocarcinoma.

A “Sin Offering” Crouching at the Door? Translation Lessons from an Exegetical Fossil in the Judson Bible

A “Sin Offering” Crouching at the Door? Translation Lessons from an Exegetical Fossil in the Judson Bible

The Challenge of Moving Evidence-Based Measures into Clinical Practice: Lessons in Knowledge Translation

Once a measure has been developed and validated, it may take years for implementation into clinical practice. The purpose of this paper is to describe strategies used to increase knowledge translation and use of the Gross Motor Function Measure (GMFM) and the Gross Motor Function Classification System (GMFCS) in clinical practice in the Netherlands and reflect on the process. Knowledge translation strategies included peer-reviewed publications, workshops, and posting information on Web sites. The impact of several of these strategies was evaluated using questionnaires focusing on therapists' self-reported familiarity and use of the measures. Peer reviewed publications did not appear to impact clinical practice. Interactive workshops were more successful at increasing use, but a gap remained between knowledge and use; the transfer into clinical practice was not optimal. A stages of change model proposed by Grol and colleagues (2007) was a helpful framework for reflecting on the process, planning, and evaluation of strategies for facilitating change in clinical practice.

Letter Regarding the Article by Xue et al, “Functional Integration of Electrically Active Cardiac Derivatives From Genetically Engineered Human Embryonic Stem Cells With Quiescent Recipient Ventricular Cardiomyocytes”

To the Editor: The article by Xue et al1 on human embryonic stem cell-derived pacemakers illustrates that embryonic stem cells differentiated into spontaneously beating cardiocytes may function as biological pacemakers and mentions a potential limitation: The intrinsic pacemaker rate was slower than desirable. They suggest that incorporating HCN pacemaker channel genes might achieve more desirable rates, an idea consistent with our published results using HCN2 in gene- and adult human mesenchymal stem cell (hMSC)-based therapies.2–4 However, certain of the comments by Xue et al misinterpret our own work on HCN-loaded hMSCs. They state that “…these modified, undifferentiated, human mesenchymal stem cells are incapable of pacing quiescent cells because the former are neither electrically active nor genuine cardiac cells” (p 19). This statement suggests a misunderstanding of the rationale and underlying biophysics of the hMSC experiments. In fact, generation of pacemaker activity does not require delivery of an “excitable differentiated cardiac cell,” but only that the delivered cell (1) carry sufficient pacemaker current and (2) make gap junctions; thus, the hMSC-myocyte pair should behave as a pacemaker unit entirely equivalent to a single heart cell with substantial if. We clearly demonstrated both …

Changes in electrical activity and ultrastructure of sinoatrial nodal cells of the rabbit's heart exposed to hypoxic solution.

HomeCirculation ResearchVol. 46, No. 2Changes in electrical activity and ultrastructure of sinoatrial nodal cells of the rabbit's heart exposed to hypoxic solution. Free AccessAbstractPDF/EPUBAboutView PDFSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessAbstractPDF/EPUBChanges in electrical activity and ultrastructure of sinoatrial nodal cells of the rabbit's heart exposed to hypoxic solution. K Nishi, Y Yoshikawa, K Sugahara and T Morioka K NishiK Nishi Search for more papers by this author , Y YoshikawaY Yoshikawa Search for more papers by this author , K SugaharaK Sugahara Search for more papers by this author and T MoriokaT Morioka Search for more papers by this author Originally published1 Feb 1980https://doi.org/10.1161/01.RES.46.2.201Circulation Research. 1980;46:201–213 Previous Back to top Next FiguresReferencesRelatedDetailsCited By Xiao A and Cho H (2020) Cellular Reprogramming Approaches to Engineer Cardiac Pacemakers, Current Cardiology Reports, 10.1007/s11886-020-01281-6, 22:5, Online publication date: 1-May-2020. Gu J, Grijalva S, Fernandez N, Kim E, Foster D and Cho H (2019) Induced cardiac pacemaker cells survive metabolic stress owing to their low metabolic demand, Experimental & Molecular Medicine, 10.1038/s12276-019-0303-6, 51:9, (1-12), Online publication date: 1-Sep-2019. Li R (2012) Gene- and cell-based bio-artificial pacemaker: what basic and translational lessons have we learned?, Gene Therapy, 10.1038/gt.2012.33, 19:6, (588-595), Online publication date: 1-Jun-2012. Fukuzaki K, Sato T, Miki T, Seino S and Nakaya H (2008) Role of sarcolemmal ATP-sensitive K + channels in the regulation of sinoatrial node automaticity: an evaluation using Kir6.2-deficient mice , The Journal of Physiology, 10.1113/jphysiol.2007.148932, 586:11, (2767-2778), Online publication date: 1-Jun-2008. Du Y and Nathan R (2007) Ionic basis of ischemia-induced bradycardia in the rabbit sinoatrial node, Journal of Molecular and Cellular Cardiology, 10.1016/j.yjmcc.2006.10.004, 42:2, (315-325), Online publication date: 1-Feb-2007. Hinescu M, Gherghiceanu M, Mandache E, Ciontea S and Popescu L (2006) Interstitial Cajal-like cells (ICLC) in atrial myocardium: ultrastructural and immunohistochemical characterization, Journal of Cellular and Molecular Medicine, 10.1111/j.1582-4934.2006.tb00306.x, 10:1, (243-257), Online publication date: 1-Jan-2006. Gryshchenko O, Qu J and Nathan R (2002) Ischemia alters the electrical activity of pacemaker cells isolated from the rabbit sinoatrial node, American Journal of Physiology-Heart and Circulatory Physiology, 10.1152/ajpheart.00833.2001, 282:6, (H2284-H2295), Online publication date: 1-Jun-2002. Saton H and Uchida T (1993) Morphological and electrophysiological changes induced by calcium ionophores (A23187 and X-537A) in spontaneously beating rabbit sino-atrial node cells, General Pharmacology: The Vascular System, 10.1016/0306-3623(93)90010-U, 24:1, (49-57), Online publication date: 1-Jan-1993. Karpel' E (1989) Electrical activity of the heart during anti-ischemic protection of the myocardium, Bulletin of Experimental Biology and Medicine, 10.1007/BF00840731, 107:6, (761-764), Online publication date: 1-Jun-1989. Bouman L, Op ‘t Hof T, Mackaay A, Bleeker W and Jongsma H (1982) On the Intrinsic Cardiac Rhythm Cardiac Rate and Rhythm, 10.1007/978-94-009-7535-4_23, (473-483), . Frasch M and Giussani D (2020) Impact of Chronic Fetal Hypoxia and Inflammation on Cardiac Pacemaker Cell Development, Cells, 10.3390/cells9030733, 9:3, (733) February 1, 1980Vol 46, Issue 2 Advertisement Article InformationMetrics Copyright © 1980 by American Heart Associationhttps://doi.org/10.1161/01.RES.46.2.201 Originally publishedFebruary 1, 1980 PDF download Advertisement

Leçons Graduèes de Traduction et de Lecture; or, Graduated Lessons in Translation and Reading, with Biographical Sketches, Annotations on History, Geography, Synonyms, and Style, and a Dictionary of Words and Idioms

Journal Article Leçons Graduèes de Traduction et de Lecture; or, Graduated Lessons in Translation and Reading, with Biographical Sketches, Annotations on History, Geography, Synonyms, and Style, and a Dictionary of Words and Idioms Get access Notes and Queries, Volume s3-I, Issue 8, 22 February 1862, Page 159, https://doi.org/10.1093/nq/s3-I.8.159f Published: 22 February 1862