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The Retinoblastoma Tumor-Suppressor Gene, the Exception That Proves the Rule
Oncogene (2006) 25, 5233–5243 & 2006 Nature Publishing Group All rights reserved 0950-9232/06 $30.00 www.nature.com/onc REVIEW The retinoblastoma tumor-suppressor gene, the exception that proves the rule DW Goodrich Department of Pharmacology & Therapeutics, Roswell Park Cancer Institute, Buffalo, NY, USA The retinoblastoma tumor-suppressor gene (Rb1)is transmission of one mutationally inactivated Rb1 allele centrally important in cancer research. Mutational and loss of the remaining wild-type allele in somatic inactivation of Rb1 causes the pediatric cancer retino- retinal cells. Hence hereditary retinoblastoma typically blastoma, while deregulation ofthe pathway in which it has an earlier onset and a greater number of tumor foci functions is common in most types of human cancer. The than sporadic retinoblastoma where both Rb1 alleles Rb1-encoded protein (pRb) is well known as a general cell must be inactivated in somatic retinal cells. To this day, cycle regulator, and this activity is critical for pRb- Rb1 remains an exception among cancer-associated mediated tumor suppression. The main focus of this genes in that its mutation is apparently both necessary review, however, is on more recent evidence demonstrating and sufficient, or at least rate limiting, for the genesis of the existence ofadditional, cell type-specific pRb func- a human cancer. The simple genetics of retinoblastoma tions in cellular differentiation and survival. These has spawned the hope that a complete molecular additional functions are relevant to carcinogenesis sug- understanding of the Rb1-encoded protein (pRb) would gesting that the net effect of Rb1 loss on the behavior of lead to deeper insight into the processes of neoplastic resulting tumors is highly dependent on biological context. -
Central Nervous System Cancers Panel Members Can Be Found on Page 1151
1114 NCCN David Tran, MD, PhD; Nam Tran, MD, PhD; Frank D. Vrionis, MD, MPH, PhD; Patrick Y. Wen, MD; Central Nervous Nicole McMillian, MS; and Maria Ho, PhD System Cancers Overview In 2013, an estimated 23,130 people in the United Clinical Practice Guidelines in Oncology States will be diagnosed with primary malignant brain Louis Burt Nabors, MD; Mario Ammirati, MD, MBA; and other central nervous system (CNS) neoplasms.1 Philip J. Bierman, MD; Henry Brem, MD; Nicholas Butowski, MD; These tumors will be responsible for approximately Marc C. Chamberlain, MD; Lisa M. DeAngelis, MD; 14,080 deaths. The incidence of primary brain tumors Robert A. Fenstermaker, MD; Allan Friedman, MD; Mark R. Gilbert, MD; Deneen Hesser, MSHSA, RN, OCN; has been increasing over the past 30 years, especially in Matthias Holdhoff, MD, PhD; Larry Junck, MD; elderly persons.2 Metastatic disease to the CNS occurs Ronald Lawson, MD; Jay S. Loeffler, MD; Moshe H. Maor, MD; much more frequently, with an estimated incidence ap- Paul L. Moots, MD; Tara Morrison, MD; proximately 10 times that of primary brain tumors. An Maciej M. Mrugala, MD, PhD, MPH; Herbert B. Newton, MD; Jana Portnow, MD; Jeffrey J. Raizer, MD; Lawrence Recht, MD; estimated 20% to 40% of patients with systemic cancer Dennis C. Shrieve, MD, PhD; Allen K. Sills Jr, MD; will develop brain metastases.3 Abstract Please Note Primary and metastatic tumors of the central nervous system are The NCCN Clinical Practice Guidelines in Oncology a heterogeneous group of neoplasms with varied outcomes and (NCCN Guidelines®) are a statement of consensus of the management strategies. -
Pearls and Forget-Me-Nots in the Management of Retinoblastoma
POSTERIOR SEGMENT ONCOLOGY FEATURE STORY Pearls and Forget-Me-Nots in the Management of Retinoblastoma Retinoblastoma represents approximately 4% of all pediatric malignancies and is the most common intraocular malignancy in children. BY CAROL L. SHIELDS, MD he management of retinoblastoma has gradu- ular malignancy in children.1-3 It is estimated that 250 to ally evolved over the years from enucleation to 300 new cases of retinoblastoma are diagnosed in the radiotherapy to current techniques of United States each year, and 5,000 cases are found world- chemotherapy. Eyes with massive retinoblas- Ttoma filling the globe are still managed with enucleation, TABLE 1. INTERNATIONAL CLASSIFICATION OF whereas those with small, medium, or even large tumors RETINOBLASTOMA (ICRB) can be managed with chemoreduction followed by Group Quick Reference Specific Features tumor consolidation with thermotherapy or cryotherapy. A Small tumor Rb <3 mm* Despite multiple or large tumors, visual acuity can reach B Larger tumor Rb >3 mm* or ≥20/40 in many cases, particularly in eyes with extrafoveal retinopathy, and facial deformities that have Macula Macular Rb location been found following external beam radiotherapy are not (<3 mm to foveola) anticipated following chemoreduction. Recurrence from Juxtapapillary Juxtapapillary Rb location subretinal and vitreous seeds can be problematic. Long- (<1.5 mm to disc) term follow-up for second cancers is advised. Subretinal fluid Rb with subretinal fluid Most of us can only remember a few interesting points C Focal seeds Rb with: from a lecture, even if was delivered by an outstanding, Subretinal seeds <3 mm from Rb colorful speaker. Likewise, we generally retain only a small and/or percentage of the information that we read, even if writ- Vitreous seeds <3 mm ten by the most descriptive or lucent author. -
Inhibitors of Mammalian Target of Rapamycin Downregulate MYCN Protein Expression and Inhibit Neuroblastoma Growth in Vitro and in Vivo
Oncogene (2008) 27, 2910–2922 & 2008 Nature Publishing Group All rights reserved 0950-9232/08 $30.00 www.nature.com/onc ORIGINAL ARTICLE Inhibitors of mammalian target of rapamycin downregulate MYCN protein expression and inhibit neuroblastoma growth in vitro and in vivo JI Johnsen1,6, L Segerstro¨ m1,6, A Orrego2, L Elfman1, M Henriksson3,BKa˚ gedal4, S Eksborg1, B Sveinbjo¨ rnsson1,5 and P Kogner1 1Department of Woman and Child Health, Karolinska Institutet, Childhood Cancer Research Unit, Stockholm, Sweden; 2Department of Oncology and Pathology, Karolinska Institutet, Stockholm, Sweden; 3Department of Microbiology, Tumor and Cellbiology, Karolinska Institutet, Stockholm, Sweden; 4Division of Clinical Chemistry, Faculty of Health Sciences, Linko¨ping University, Sweden and 5Department of Cell Biology and Histology, University of Tromso¨, Tromso¨, Norway Mammalian target of rapamycin (mTOR) has been shown the most common and deadly solid tumor of childhood to play an important function in cell proliferation, (Brodeur, 2003). Amplification of the MYCN oncogene metabolism and tumorigenesis, and proteins that regulate is associated with rapid tumor progression and fre- signaling through mTOR are frequently altered in human quently detected in advanced-stage neuroblastoma, but cancers. In this study we investigated the phosphorylation is also a major negative prognostic factor in localized status of key proteins in the PI3K/AKT/mTOR pathway tumors (Schwab et al., 2003). Advanced-stage tumors and the effects of the mTOR inhibitors rapamycin and and those with MYCN amplification show typically CCI-779 on neuroblastoma tumorigenesis. Significant emergence of treatment resistance, and alternative expression of activated AKT and mTOR were detected treatment strategies for these patients are therefore in all primary neuroblastoma tissue samples investigated, urgently needed. -
Metabolic Profiling of the Three Neural Derived Embryonal Pediatric Tumors
Metabolic profiling of the three neural derived embryonal pediatric tumors retinoblastoma, neuroblastoma and medulloblastoma, identifies distinct metabolic profiles Kohe, Sarah; Bennett, Christopher; Gill, Simrandip; Wilson, Martin; McConville, Carmel; Peet, Andrew DOI: 10.18632/oncotarget.24168 License: Creative Commons: Attribution (CC BY) Document Version Publisher's PDF, also known as Version of record Citation for published version (Harvard): Kohe, SE, Bennett, CD, Gill, SK, Wilson, M, McConville, C & Peet, AC 2018, 'Metabolic profiling of the three neural derived embryonal pediatric tumors retinoblastoma, neuroblastoma and medulloblastoma, identifies distinct metabolic profiles', OncoTarget, vol. 9, no. 13, pp. 11336-11351. https://doi.org/10.18632/oncotarget.24168 Link to publication on Research at Birmingham portal General rights Unless a licence is specified above, all rights (including copyright and moral rights) in this document are retained by the authors and/or the copyright holders. The express permission of the copyright holder must be obtained for any use of this material other than for purposes permitted by law. •Users may freely distribute the URL that is used to identify this publication. •Users may download and/or print one copy of the publication from the University of Birmingham research portal for the purpose of private study or non-commercial research. •User may use extracts from the document in line with the concept of ‘fair dealing’ under the Copyright, Designs and Patents Act 1988 (?) •Users may not further distribute the material nor use it for the purposes of commercial gain. Where a licence is displayed above, please note the terms and conditions of the licence govern your use of this document. -
1P36 Tumor Suppression—A Matter of Dosage?
Published OnlineFirst November 20, 2012; DOI: 10.1158/0008-5472.CAN-12-2230 Cancer Review Research 1p36 Tumor Suppression—A Matter of Dosage? Kai-Oliver Henrich, Manfred Schwab, and Frank Westermann Abstract A broad range of human malignancies is associated with nonrandom 1p36 deletions, suggesting the existence of tumor suppressors encoded in this region. Evidence for tumor-specific inactivation of 1p36 genes in the classic "two-hit" manner is scarce; however, many tumor suppressors do not require complete inactivation but contribute to tumorigenesis by partial impairment. We discuss recent data derived from both human tumors and functional cancer models indicating that the 1p36 genes CHD5, CAMTA1, KIF1B, CASZ1, and miR-34a contribute to cancer development when reduced in dosage by genomic copy number loss or other mechanisms. We explore potential interactions among these candidates and propose a model where heterozygous 1p36 deletion impairs oncosuppressive pathways via simultaneous downregulation of several dosage-dependent tumor suppressor genes. Cancer Res; 72(23); 1–10. Ó2012 AACR. Introduction (Fig. 1; refs. 1, 17–29). Despite extensive 1p36 candidate gene Deletions of the distal short arm of chromosome 1 (1p) are sequence analyses, success was limited for identifying tumor- fi frequently observed in a broad range of human cancers, speci c mutations in neuroblastomas or other malignancies, including breast cancer, cervical cancer, pancreatic cancer, which led some to conclude that a deletion mapping approach pheochromocytoma, thyroid cancer, hepatocellular cancer, was unlikely to deliver tumor suppressor genes. Many tumor colorectal cancer, lung cancer, glioma, meningioma, neuro- suppressor genes, however, do not require inactivation in a blastoma, melanoma, Merkel cell carcinoma, rhabdomyosar- classic "two-hit" manner but contribute to tumor development coma, acute myeloid leukemia, chronic myeloid leukemia, and when their dosage is reduced, sometimes only subtly, by non-Hodgkin lymphoma (1, 2). -
Strabismus: a Decision Making Approach
Strabismus A Decision Making Approach Gunter K. von Noorden, M.D. Eugene M. Helveston, M.D. Strabismus: A Decision Making Approach Gunter K. von Noorden, M.D. Emeritus Professor of Ophthalmology and Pediatrics Baylor College of Medicine Houston, Texas Eugene M. Helveston, M.D. Emeritus Professor of Ophthalmology Indiana University School of Medicine Indianapolis, Indiana Published originally in English under the title: Strabismus: A Decision Making Approach. By Gunter K. von Noorden and Eugene M. Helveston Published in 1994 by Mosby-Year Book, Inc., St. Louis, MO Copyright held by Gunter K. von Noorden and Eugene M. Helveston All rights reserved. No part of this publication may be reproduced, stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, recording, or otherwise, without prior written permission from the authors. Copyright © 2010 Table of Contents Foreword Preface 1.01 Equipment for Examination of the Patient with Strabismus 1.02 History 1.03 Inspection of Patient 1.04 Sequence of Motility Examination 1.05 Does This Baby See? 1.06 Visual Acuity – Methods of Examination 1.07 Visual Acuity Testing in Infants 1.08 Primary versus Secondary Deviation 1.09 Evaluation of Monocular Movements – Ductions 1.10 Evaluation of Binocular Movements – Versions 1.11 Unilaterally Reduced Vision Associated with Orthotropia 1.12 Unilateral Decrease of Visual Acuity Associated with Heterotropia 1.13 Decentered Corneal Light Reflex 1.14 Strabismus – Generic Classification 1.15 Is Latent Strabismus -
Strabismus Developing After Unilateral and Bilateral Cataract Surgery in Children
Eye (2016) 30, 1210–1214 © 2016 Macmillan Publishers Limited, part of Springer Nature. All rights reserved 0950-222X/16 www.nature.com/eye CLINICAL STUDY Strabismus developing R David, J Davelman, H Mechoulam, E Cohen, I Karshai and I Anteby after unilateral and bilateral cataract surgery in children Abstract Purpose To evaluate the prevalence and common in children with poor final visual risk factors of strabismus in children acuity. undergoing surgery for unilateral or bilateral Eye (2016) 30, 1210–1214; doi:10.1038/eye.2016.162; cataract with or without intraocular lens published online 29 July 2016 implantation. Methods Medical records of pediatric Introduction patients were evaluated from 2000 to 2011. Children undergoing surgery for unilateral The rate of strabismus associated with cataract or bilateral cataract with at least 1 year of in children has been reported to range from follow-up were included. Children with 20.5 to 86%.1 Strabismus is more prevalent in ocular trauma, prematurity, or co-existing children who have been operated for cataract systemic disorders were excluded. The than in the general pediatric population.2–8 following data were evaluated: strabismus Moreover, it occurs more frequently in patients pre- and post-operation; age at surgery; with unilateral than bilateral cataract.1 The post-operative aphakia or pseudophakia; association between timing of surgery or the use and visual acuity. of intra ocular lens (IOL) with development of Results Ninety patients were included, 40% strabismus is still not fully understood. had unilateral and 60% had bilateral cataracts. The main purpose of this study is to evaluate Follow-up was on average 51 months (range: the prevalence and risk factors of strabismus 12–130 months). -
Adult Strabismus Overview Common Types Esotropia Exotropia
Gregory Ostrow, M.D. Scripps Clinic/Scripps Green Hospital Grand Rounds Wednesday, Mar. 18, 2009 Overview • Common Types of Strabismus • Indications for Strabismus Surgery • Common Procedures Adult Strabismus • Psychosocial Benefits Gregory Ostrow M.D Pediatric Ophthalmology and Adult Strabismus Scripps Clinic Medical Group 3811 Valley Centre Drive San Diego, CA 92130 Esotropia Common Types Exotropia www.scripps.org/clinicrss Scripps Conference Services & CME www.scripps.org/conferenceservices 1 P: (858) 652-5400 E: [email protected] Gregory Ostrow, M.D. Scripps Clinic/Scripps Green Hospital Grand Rounds Wednesday, Mar. 18, 2009 • There are many different Indications for Strabismus presentations of strabismus Surgery • Most can be corrected surgically Classically Taught Benefits of Other Benefits Strabismus Surgery • Develop binocular vision • Improve visual • Restore binocular vision field • Eliminate diplopia • Eliminate torticollis www.scripps.org/clinicrss Scripps Conference Services & CME www.scripps.org/conferenceservices 2 P: (858) 652-5400 E: [email protected] Gregory Ostrow, M.D. Scripps Clinic/Scripps Green Hospital Grand Rounds Wednesday, Mar. 18, 2009 Insurance accepted indications Surgical Procedures for strabismus surgery •Diplopia • Weaken (recession) • Asthenopia (eye strain) • Strengthen (resection or tuck) • Any misalignment of the eyes that • Alter vector forces (transposition) cannot be corrected non-surgically – this is where some prodding is occasionally required Recession (weakening) www.scripps.org/clinicrss Scripps Conference Services & CME www.scripps.org/conferenceservices 3 P: (858) 652-5400 E: [email protected] Gregory Ostrow, M.D. Scripps Clinic/Scripps Green Hospital Grand Rounds Wednesday, Mar. 18, 2009 Resection (tightening) Psychosocial Benefits of Strabismus Surgery www.scripps.org/clinicrss Scripps Conference Services & CME www.scripps.org/conferenceservices 4 P: (858) 652-5400 E: [email protected] Gregory Ostrow, M.D. -
Retinoblastoma
A Parent’s Guide to Understanding Retinoblastoma 1 Acknowledgements This book is dedicated to the thousands of children and families who have lived through retinoblastoma and to the physicians, nurses, technical staf and members of our retinoblastoma team in New York. David Abramson, MD We thank the individuals and foundations Chief Ophthalmic Oncology who have generously supported our research, teaching, and other eforts over the years. We especially thank: Charles A. Frueauf Foundation Rose M. Badgeley Charitable Trust Leo Rosner Foundation, Inc. Invest 4 Children Perry’s Promise Fund Jasmine H. Francis, MD The 7th District Association of Masonic Lodges Ophthalmic Oncologist in Manhattan Table of Contents What is Retinoblastoma? ..........................................................................................................3 Structure & Function of the Eye ...........................................................................................4 Signs & Symptoms .......................................................................................................................6 Genetics ..........................................................................................................................................7 Genetic Testing .............................................................................................................................8 Examination Schedule for Patients with a Family History ........................................ 10 Retinoblastoma Facts ................................................................................................................11 -
Refraction of 1-Year-Old Children After Atropine Cycloplegia R
Br J Ophthalmol: first published as 10.1136/bjo.63.5.343 on 1 May 1979. Downloaded from British Journal of Ophthalmology, 1979, 63, 343-347 Refraction of 1-year-old children after atropine cycloplegia R. M. INGRAM From the Kettering and District General Hospital, Kettering SUMMARY The refractions of 1648 children aged 11 to 13 months are reported. Atropine % was used for cycloplegia. 11 83% of the children had bilateral hypermetropia of +2O00 or more D. 13-23 % of them had + 1 50 or more D astigmatism in one or both eyes, and 6 5 % had anisometropia. Anisometropia was significantly (P=0-000 001 %) associated with bilateral hypermetropia, but even more significantly (P=0000000 4%) associated with astigmatism of +1 50 or more D in one or both eyes. Cyclopentolate was used in our pilot study (Ingram month of their birth, but some children born late et al., 1979) for reasons of convenience, but its in the month were refracted early in that month cycloplegic effect has not been proved (Davidson, and others, for one reason or another, attended 1976). Atropine is accepted generally as the most during the following month. Thus their ages ranged efficient cycloplegic drug, and the true range of from 11 to 13 months inclusive. refractions at age 1 year would be more accurately All the refractions were carried out by the recorded after 'atropinisation'. This is a report of author. When cycloplegia was obviously incomplete, the refractions of 1648 1-year-old children examined for example, the pupils were mobile or when the after 'full atropinisation'. -
COMMON EYE COMPLAINTS July 15, 2004 Vatinee Bunya
4/24/2018 They have a lazy eye… Be Specific!! Esotropia vs. Pseudoesotropia Eyes crossing (esotropia) Eyes drifting (exotropia) Head turn Droopy eyelid Vision concerns 1 4/24/2018 www.aapos.org/terms/conditions/49 Vertical strabismus Ocular torticollis Nystagmus Finding their null point Strabismus Fusion or less strain Ptosis Chin up to see below lids Refractive Error Squinting equivalent Amblyopia Amblyopia Three main reasons for amblyopia Refractive Greater than 2 lines difference in visual ○ high myopia/hyperopia or acuity or obvious preference for fixation in anisometropia non-verbal Strabismic Induced tropia test ○ Esotropia or exotropia or hypertropia ○ Take 12 pd base down over both eyes Deprevational ○ Symmetric response= no preference ○ Cataract, corneal opacity, vitreous ○ Asymmetric response= amblyopia hemorrhage, ptosis, hemangioma 2 4/24/2018 Their eyelid is swollen… Amblyopia Treatment Force brain to use weaker eye Fix underlying etiology (give glasses, fix strab remove cataract,etc) Patch Atropine Occluding CL Fog glasses No-No arm braces Super glue Management Stye/Chalazion Stye vs. Chalazion Warm compresses Lid hygiene Erythromycin vs. Maxitrol/Tobradex Surgical excision Cellulitis Can they open their eyelids on their own? Preseptal vs. Can you get the eyelids open? Postseptal Cellulitiss 3 4/24/2018 Treatment Orbital cellulitis Results from Antiobiotics Local resistance patterns Spread of contiguous sinus disease (most common) ○ 75-85% of cases are chronic sinusitis (acute 0.5-3%) Check blood cultures first ○ Most commonly ethmoid aircells To drain or not to drain? Traumatic violation of the orbit (implantation of Worrisome optic neuropathy foreign bodies) signs Trans-septal spread of preseptal cellulitis Abscess within orbit Metastatic hematogenous spread to orbit ○ not subperiosteal ○ Valveless orbital veins Treatment failures Dental abscess to orbit Orbital cellulitis My child’s eye is red… Common organisms Staphylcoccus Aureus Streptococcus species Anaerobic If <4 years old consider H.