DOCSLIB.ORG

Evaluating and Controlling Glioblastoma Infiltration by Joseph

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Evaluating and Controlling Glioblastoma Infiltration by Joseph Evaluating and Controlling Glioblastoma Infiltration by Joseph F. Georges A Dissertation Presented in Partial Fulfillment of the Requirements for the Degree Doctor of Philosophy Approved March 2014 by the Graduate Supervisory Committee: Burt Feuerstein, Co-Chair Brian Smith, Co-Chair Kendall Van Keuren-Jensen Pierre Deviche Kevin Bennett ARIZONA STATE UNIVERSITY May 2014 ABSTRACT Glioblastoma (GBM) is the most common primary brain tumor with an incidence of approximately 11,000 Americans. Despite decades of research, average survival for GBM patients is a modest 15 months. Increasing the extent of GBM resection increases patient survival. However, extending neurosurgical margins also threatens the removal of eloquent brain. For this reason, the infiltrative nature of GBM is an obstacle to its complete resection. The central hypothesis of this dissertation is that targeting genes and proteins that regulate GBM motility, and developing techniques that safely enhance extent of surgical resection, will improve GBM patient survival by decreasing infiltration into eloquent brain regions and enhancing tumor cytoreduction during surgery. Chapter 2 of this dissertation describes a gene and protein; aquaporin-1 (aqp1) that enhances infiltration of GBM. In chapter 3, a method is developed for enhancing the diagnostic yield of GBM patient biopsies which will assist in identifying future molecular targets for GBM therapies. In chapter 4, an intraoperative optical imaging technique is developed for improving identification of GBM and its infiltrative margins during surgical resection. This dissertation aims to target glioblastoma infiltration from molecular and cellular biology and neurosurgical disciplines. In the introduction; 1. A background of GBM and current therapies is provided. 2. A protein that decreases GBM survival is discussed. 3. An imaging modality utilized for improving the quality of accrued GBM patient samples is described. 4. An overview of intraoperative contrast agents available for neurosurgical resection of GBM, and discussion of a new agent for intraoperative visualization of GBM is provided. i ACKNOWLEDGMENTS I would like to express the greatest appreciation to my advisor, Burt Feuerstein MD/PhD. Burt selflessly prioritized my training as a graduate student, and spent substantial time mentoring me in experiment design, data analysis, scientific writing, and grantsmanship. He taught me the value of collaborative research, and helped me acquire training at highly regarded research institutes. Burt always had a plan for my continued growth as a physician-scientist. This was evident in the numerous educational opportunities he provided for me in clinical neuroscience. Without Burt’s mentoring and support, this dissertation would not have been possible. I would also like to thank my committee for supporting my development as a scientist, and creating opportunities for my continued learning. I thank Kendall Van Keuren-Jensen for the countless times she allowed me to interrupt her work to casually chat about neuroscience and experiment design. I also thank Kevin Bennett for providing me opportunities to learn MRI, and for the great memories of working with him and his students. I am grateful to Pierre Deviche for serving as my undergraduate research mentor beginning in 2003, providing me opportunities to work on neuroendocrine projects, and making graduate school a possibility for me. I would also like to thank Brian Smith for his part in creating the interdisciplinary neuroscience program between Arizona State University and Barrow Neurological Institute (ASU-BNI), and for his personal support during graduate school. Additionally, I thank Trent Anderson and Peter Nakaji for their friendship and mentoring during graduate school. Trent helped me troubleshoot many experiments and always provided great advice towards improving manuscripts. I enjoyed working with ii Peter Nakaji at BNI. Dr Nakaji strongly mentored me in clinical neurosurgery research, and he provided me endless opportunities to design and implement molecular imaging projects. My training as a physician-scientist would not have been possible without the infrastructure and research opportunities created by faculty at ASU-BNI. I would like to thank the researchers who have made this program a great educational experience for myself and fellow classmates. I would also like to thank the labmates I have enjoyed working with in graduate school. I am grateful for your support during my training and the great times we shared working together. Also, I would like thank my wife Jackie and my family who supported and encouraged me throughout medical and graduate school. iii TABLE OF CONTENTS Page LIST OF TABLES .................................................................................................................... v LIST OF FIGURES ................................................................................................................. vi CHAPTER 1 INTRODUCTION .......................................................................................................1 2A AQUAPORIN 1 PREDICTS SURVIVAL OF MALIGNANT GLIOMA PATIENTS AND INCREASES GLIOMA CELL INVASIVENESS ..................................................... 14 Introduction .............................................................................................. 15 Materials and Methods ............................................................................. 17 Results ...................................................................................................... 25 Discussion ................................................................................................ 38 Conclusion ................................................................................................ 41 References ................................................................................................ 44 2B AQUAPORIN-1 OVEREXPRESSION ENHANCES GLIOMA CELL MOTILITY INDEPENDENTLY OF WATER TRANSPORT ............................................................. 47 Introduction .............................................................................................. 47 Materials and Methods ............................................................................. 49 Results ...................................................................................................... 51 Discussion ................................................................................................ 59 References ................................................................................................ 61 iv CHAPTER Page 3 CONTRAST-FREE MICROSCOPIC ASSESSMENT OF GLIOBLASTOMA BIOSPECIMENS PRIOR TO BIOBANKING ………………………………….…………63 Introduction .............................................................................................. 64 Materials and Methods ............................................................................. 68 Results ...................................................................................................... 71 Discussion ................................................................................................ 77 Conclusion ................................................................................................ 79 References ................................................................................................ 80 4 RAPID AND SPECIFIC DIAGNOSIS OF HUMAN ASTROCYTIC BRAIN TUMORS BY IMMEDIATE EX VIVO IMAGING WITH SULFORHODAMINE 101 82 Introduction .............................................................................................. 83 Materials and Methods ............................................................................. 85 Results ...................................................................................................... 90 Discussion .............................................................................................. 101 Conclusion .............................................................................................. 103 References .............................................................................................. 107 5 DISCUSSION ................... .............................................................................................. 110 REFERENCES....... ................................................................................................................. 117 APPENDIX A: Cirriculum Vitae ........................................................................................... 123 APPENDIX B: AQP1 and Glioblastoma Infiltration .............................................................. 129 APPENDIX C: Sulforhodamine 101 Specifically Labels Human Astrocytoma .................... 131 APPENDIX D: Reflectance Microscopy Screening of Glioblastoma Biospecimens ............. 133 v LIST OF TABLES Table Page 1. Characteristics of patients examined for aqp1 expression .................................. 42 2. Aqp1 expression is an independent predictor of survival ................................... 43 3. Distribution of human biopsies stained with SR101 and final diagnosis .......... 105 4. Stereology counts per region of interest ............................................................ 106 vi LIST OF FIGURES Figure Page 1. Aquaporin-1 expression is prognostic in GBM ............................................ 27 2. AQP1 overexpression enhances U251 motility ............................................ 29 3. AQP1 enhances matrigel invasion. ..............................................................
Load more

Recommended publications
  • EPILEPSY and Eegs in BOSTON, BEGINNING at BOSTON CITY HOSPITAL
    EPILEPSY AND EEGs IN BOSTON, BEGINNING AT BOSTON CITY HOSPITAL Frank W. Drislane, MD Beth Israel Deaconess Medical Center Harvard Medical School Boston, MA Early Neurology at Harvard Medical School: In the 1920s and 1930s: Neurology and Psychiatry were largely one field. “All practitioners of the specialty [Neurology] were neuropsychiatrists” -- Merritt: History of Neurology (1975) 1923: David Edsall, first full-time Dean at Harvard Medical School “creates a Department of Neurology to build on the fame of James Jackson Putnam” [1] 1928: Harvard, Penn, and Montefiore-Columbia were the only Neurology departments in the US. 1930: The Harvard Medical School Neurology service at Boston City Hospital, one of the first training centers in the US, founded by Stanley Cobb 1935: American Board of Psychiatry and Neurology 1936: “There were only 16 hospitals listed in the United States a having approved training for residency in Neurology.” [1] 1947: There are 32 Neurology residency positions in the US 1948: Founding of the American Academy of Neurology Stanley Cobb (1887 – 1968) 1887: Brahmin, born in Boston. Speech impediment. 1914: Harvard Medical School grad, after Harvard College Studied Physiology at Hopkins 1919: Physiology research with Walter B Cannon and Alexander Forbes at Harvard 1925: Appointed Bullard Professor of Neuropathology at Harvard Medical School {Successors: Raymond Adams, E Pierson Richardson, Joseph Martin} Interested in Neurology and Psychiatry, and particularly, epilepsy and its relation to cerebral blood flow 1925: Starts the Neurology program at Boston City Hospital (with financial support from Abraham Flexner) Faculty include: Harold Wolff (headaches; cerebral circulation; founder of Cornell Neurology Department), Paul Yakovlev, Sam Epstein Cobb’s Neuropathology group at the HMS medical school campus includes William Lennox 1928: Cobb hires Tracy Putnam for a research position in the Neurosurgery division; Houston Merritt arrives as a resident © 2017 The American Academy of Neurology Institute.
    [Show full text]
  • Percival Bailey and the Classification of Brain Tumors
    Neurosurg Focus 18 (4):E7, 2005 Percival Bailey and the classification of brain tumors SHERISE FERGUSON, M.A., AND MACIEJ S. LESNIAK, M.D. Division of Neurosurgery, The University of Chicago Pritzker School of Medicine, Chicago, Illinois Throughout his illustrious career, Percival Bailey made numerous contributions to the fields of neurology, neu- roanatomy, psychiatry, neuropathology, and, of course, neurosurgery. His expertise, his curiosity about the nervous system, and his desire to examine it from all angles were unique. With the exception of Harvey Cushing, Dr. Bailey made some of the greatest contributions in the area of neuro-oncology at the turn of the last century. In this essay the authors summarize the key episodes of Bailey’s life and discuss his impact on the classification and treatment of human brain tumors. KEY WORDS • Percival Bailey • brain tumor • meningioma • glioma • tumor classification • neurosurgical history Percival Bailey was born in 1892 in the southernmost routine dissection of the pituitary, Bailey unintention- part of Illinois, a rural area known as “Little Egypt.” He ally damaged the infundibular artery. At the time, Bailey spoke warmly of his memories of childhood and growing thought his mistake was an incredible blunder. Neverthe- up in this small town in his autobiography, Up from Little less, the next morning he found a large pool of urine on Egypt.8 Bailey’s early education took place in a one-room the floor next to the dog. To his surprise, he realized that schoolhouse and then at Southern Illinois Normal Univer- he had produced polyuria without exposing the pituitary sity.
    [Show full text]
  • Tumor Heterogeneity in Glioblastomas: from Light Microscopy to Molecular Pathology
    cancers Review Tumor Heterogeneity in Glioblastomas: From Light Microscopy to Molecular Pathology Aline P. Becker 1,* , Blake E. Sells 2 , S. Jaharul Haque 1 and Arnab Chakravarti 1 1 Comprehensive Cancer Center, Ohio State University, Columbus, OH 43210, USA; [email protected] (S.J.H.); [email protected] (A.C.) 2 Medical Scientist Training Program, Washington University in St. Louis, St. Louis, MO 63310, USA; [email protected] * Correspondence: [email protected] Simple Summary: Glioblastomas (GBMs) are the most frequent and aggressive malignant tumors arising in the human brain. One of the main reasons for GBM aggressiveness is its diverse cellular composition, comprised by differentiated tumor cells, tumor stem cells, cells from the blood vessels, and inflammatory cells, which simultaneously affect multiple cellular functions involved in cancer development. “Tumor Heterogeneity” usually encompasses both inter-tumor heterogeneity, differ- ences observed at population level; and intra-tumor heterogeneity, differences among cells within individual tumors, which directly affect outcomes and response to treatment. In this review, we briefly describe the evolution of GBM classification yielded from inter-tumor heterogeneity studies and discuss how the technological development allows for the characterization of intra-tumor hetero- geneity, beginning with differences based on histopathological features of GBM until the molecular alterations in DNA, RNA, and proteins observed at individual cells. Citation: Becker, A.P.; Sells, B.E.; Abstract: One of the main reasons for the aggressive behavior of glioblastoma (GBM) is its intrinsic Haque, S.J.; Chakravarti, A. Tumor intra-tumor heterogeneity, characterized by the presence of clonal and subclonal differentiated tumor Heterogeneity in Glioblastomas: cell populations, glioma stem cells, and components of the tumor microenvironment, which affect From Light Microscopy to Molecular multiple hallmark cellular functions in cancer.
    [Show full text]
  • The Neuropsychology of Sigmund Freud
    Reprinted from EXPERIMENTAL FOUNDATIONS OF CLINI­ CAL PSYCHOLOGY, edited by Arthur J. Bachrach. Copyright 1962 by Basic Books Publishing Co., Inc. 13 The Neuropsychology of Sigmund Freud KARL H. PRIBRAM The experimental foundations of clinical psychology deal, for the most part, with investigations of psychopathology. There is found another, somewhat less prevalent theme, however, characterized by an em­ phasis on basic, theory-directed questions. Clinical material is used as a caricature of the theoretical problem, and the hope is that better theory will be attained when the clinical phenomenon is related to laboratory experience. There is one branch of clinical endeavor that consistently uses this method: clinical neurology. <) Pathological ma­ terial is used to gain a better understanding not only of the abnormali­ ties in question but also of the fundamental workings of the brain and its regulation of behavior. John Hughlings Jackson, Henry Head, Otto Foerster, Harvey Cushing, Percival Bailey, Wilder Penfield, D. Denny­ Brown and F. M. R. Walshe are only a few names that attest to this tradition. Much of clinical psychology today either takes for granted or makes actual investigations of notions which can be directly traced back to Sigmund Freud. Many of the chapters in this book detail experimental o As I indicated in a recent paper on the interrelations between psychology and the neurological sciences (1962), clinical neurology is, to a large extent, a neuropsychological discipline; namely, the investigation of neurological proc­ esses-normal and pathological-by behavioral techniques. Perhaps partly be­ cause of the poor prognosis attached to diseases of the central nervous system, and partly because of the difficulties in the mastery of neurological knowledge in the first place, clinical neurologists have invariably used clinical material to pose basic, i.e., theory-directed questions.
    [Show full text]
  • History of Epilepsy Surgery
    eCommons@AKU Section of Neurosurgery Department of Surgery 4-2007 History of epilepsy surgery Ather Enam Aga Khan University, [email protected] Follow this and additional works at: https://ecommons.aku.edu/pakistan_fhs_mc_surg_neurosurg Part of the Neurology Commons, Neurosurgery Commons, and the Surgery Commons Recommended Citation Enam, A. (2007). History of epilepsy surgery. Pakistan Journal of Neurological Sciences, 2(2), 129-129. Available at: https://ecommons.aku.edu/pakistan_fhs_mc_surg_neurosurg/78 V I G N E T T E HISTORY OF EPILEPSY SURGERY S. Ather Enam Aga Khan University The history of epilepsy surgery is as old Unfortunately he could not as the roots of modern neurosurgery. fulfill his dream but did build a Surgical intervention to cure epilepsy neurosurgical department of can be traced back to occasional distinction at that institution. reports from France and England of relief of post-traumatic epilepsy by The duo that eventually brought trephination in the early 19th century. epilepsy surgery to the Trained among these European knowledge of common people surgeons, the American Benjamin was Wilder Penfield and Benjamin Winslow Winslow Dudley (1785-1870; left) at Herbert Jasper. Penfield Dudley Transylvania Medical School in (1891-1976), born in Lexington, Kentucky, was the first one to publish a series of Spokane, Washington, was reports of trephination for post-traumatic epilepsy. Four out initially not interested in L tp R: Percival Bailey, of five patients were relieved of their seizures. A success of medicine as he saw his father Erna and Frederick Gibbs almost 80% is very impressive especially considering the fail in his medical practice fact that this was a pre-Listerian and pre-anesthesia era.
    [Show full text]
  • New Radiological Classification of Glioma and Validation with the Survival Analysis
    bioRxiv preprint doi: https://doi.org/10.1101/2020.02.28.969493; this version posted February 28, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY 4.0 International license. New Radiological Classification of Glioma and validation with the survival analysis Short title: New radiological classification of glioma Akshaykumar Nana Kamble 1, FRCR*; Nidhi K Agrawal 2, DNB; Surabhi Koundal1, MBBS; Salil Bhargava 3, DNB; Abhaykumar Nana Kamble 4, B.E Affiliations: 1. Institute of nuclear medicine and allied sciences (INMAS), Delhi 2. Max Super-specialty Hospital, Mohali 3. Sir Ganga Ram Hospital, Delhi 4. Saraswati College of Engineering, Mumbai Corresponding author and First author* Email: [email protected] bioRxiv preprint doi: https://doi.org/10.1101/2020.02.28.969493; this version posted February 28, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY 4.0 International license. Abstract Radiology based classification of glioma independent of histological or genetic markers predicting survival of patients is an unmet need. Until now radiology is chasing these markers rather than focussing directly on the clinical outcome. Our study is first of its kind to come up with the independent new radiological classification of gliomas encompassing both low-and high-grade gliomas under single classification system.
    [Show full text]
  • Hans Joachim Scherer and His Impact on the Diagnostic, Clinical, and Modern Research Aspects of Glial Tumors
    Open Access Review Article DOI: 10.7759/cureus.6148 Hans Joachim Scherer and His Impact on the Diagnostic, Clinical, and Modern Research Aspects of Glial Tumors George S. Stoyanov 1 , Lilyana Petkova 1 , Deyan L. Dzhenkov 1 1. General and Clinical Pathology, Forensic Medicine and Deontology, Medical University of Varna, Varna, BGR Corresponding author: George S. Stoyanov, [email protected] Abstract The historical descriptions of glial tumors are often poorly understood and interpreted. The gross and histological depictions of glial tumors are often credited to Virchow, and while the first true histological description is truly his, gross descriptions can be traced back to the beginning of the 1800s, with their classification and histogenesis attributed to Percival Bailey and Harvey Cushing. Without any question, the most prominent and under-credited researcher in the field of glioma pathobiology was the German neuropathologist Hans Joachim Scherer. Despite the limited armamentarium available to him, his systematic approach led to conclusions, some of which have now been molecularly explained today while some are still being widely researched. Scherer defined pseudopalisadic necrosis as a pathognomonic feature of glioblastoma multiforme (GBM), as well as secondary features due to tumor growth, known collectively as secondary Scherer figures, for example, neuronal and vascular satellitosis, tract and subpial aggregation. All these features are key points in the modern histological diagnosis of glial tumors. Other contributions by Scherer include the definition of glomeruloid vascular proliferation and his conclusion that they are caused by vascular factors released by the tumor, decades before vascular endothelial growth factor and its receptors were discovered and their role in glioma evolution was established.
    [Show full text]
  • Past ABPN Giants in Neurology
    ABPN 75th Anniversary Celebration Giants of Neurology Mark L Dyken, MD Professor Emeritus of Neurology Indiana University Medical School September 26, 2009 ABPN “NEUROLOGY GIANTS” (American Neurological Association & American Academy of Neurology” ANA Presidents 1. Lewis J. Pollock 1942 2. Edwin G. Zabriskie 1944 3. Henry W. Woltman 1950 4. Hans H. Reese 1953 5. Roland P . Mackay 1954 6. Percival Bailey 1955 7. Johannes M. Nielsen 1956 8. H. Houston Merritt 1957 AAN Presidents 9. Bernard J. Alpers 1959 1. Abe B. Baker* 1948-1951 10.RllDJRussell DeJong 1965 2. FiMFtFrancis M. Forster 1957-1959 11.Adolph L. Sahs 1968 3. Augustus S. Rose* 1959-1961 12.Augustus S. Rose 1969 4. Adolph L. Sahs* 1961-1963 13.Melvin D. Yahr 1970 5. Sidney Carter 1969-1971 14.Abe B. Baker 1971 *Also ANA ANA Vice Presidents 1. Louis Casamajor 1939 2. Frederich P. Moersch 1952 3. Alphonse Vonderahe 1955 4. Paul I. Yakovlev 1959 5. Charles Rupp 1960 6. Knox Finley 1963 7. Alexander T. Ross 1967 •M.D. 1906 College of Physicians and Surgeons •1909 -1948 New York Neurological Institute . Assistant Attending to Professor Emeritus. •Early interest in Child Neurology followed Bernard Sachs and was followed by Sidney Carter and then Darryl DeVivo •President of several psychiatric societies, but defensive about N before P in ABPN, •“Neurologists, you know, have much more reverence for the alphabet than psychiatrists have.” •"Personally I don't give a damn …” One of most colorful and the most controversial of all ABPN directors. ((yThe Lobotomist: by Jack El-Hai , Last Resort: Psychosurgery and Limits of Medicine by Pressman JD.
    [Show full text]
  • Percival Bailey
    Percival Bailey 1892-1973 PERCIVAL BAILEY was born prematurely on May 9, 1892 in Mt. Vernon, Illinois while his mother was visiting there. He was christened Percival Sylvester Bailey, but the Sylvester was dropped very early. However, since he disliked the abbreviation of Percival to Percy, he used the name Ves until he went to college. He grew up near Springerton, Illinois. He attended Southern Illinois Normal School at Carbondale, Illinois, was a Phi Beta Kappa Ph.D. graduate from the University of Chicago, and attended medical school in Chicago at Rush, Northwestern. He began his neurosurgical training in Harvey Cushing’s Clinic in Boston. However, Cushing was just organizing his program at Peter Bent Brigham, so Bailey returned to Chicago for a year on the Neurology and Psychiatry wards at Cook County Hospital. He then went to Europe, where the clinics of the Salpetriere stimulated his desire to return to Cushing’s service, where he hoped to utilize his newly acquired knowledge of Cajal’s neuroanatomical techniques. He adapted these techniques to the glial tumors of the nervous system, which Cushing had accumulated. After over two years of work with Cushing’s tumors, he proposed a classification of the gliomas of the nervous system, based on the embryology of the brain. In their classic monograph, Cushing and Bailey correlated the pathological picture of tumors with their clinical history. A subsequent series of papers in collaboration with colleagues and pupils extended this classification to include rarer types and the meningeal neoplasms. In 1928, he was appointed Professor of Neurology and Neurosurgery at the University of Chicago, a position he held until 1941.
    [Show full text]
  • PERCIVAL BAILEY May 9, 1892-August 10, 1973
    NATIONAL ACADEMY OF SCIENCES P ERCIVAL BAILEY 1892—1973 A Biographical Memoir by P A U L C . B UCY Any opinions expressed in this memoir are those of the author(s) and do not necessarily reflect the views of the National Academy of Sciences. Biographical Memoir COPYRIGHT 1989 NATIONAL ACADEMY OF SCIENCES WASHINGTON D.C. PERCIVAL BAILEY May 9, 1892-August 10, 1973 BY PAUL C. BUCY HE BARREN CLAY HILLS of southern Illinois did not pro- Tduce good corn or hogs, but they produced superb men. This southernmost section of Illinois is formed by the Ohio River on the southeast, by the Mississippi River on the south- west, and by an indefinite, irregular line running from a few miles north of St. Louis, Missouri, east to the Wabash River. This triangle has long been known as "Little Egypt" and ap- propriately has Cairo, located at the apex of the triangle and the junction of the Ohio and Mississippi rivers, as its capital. The unproductiveness of Little Egypt led to poverty. It seems very likely that this poverty was the force that drove many intelligent young people to head North (generally to Chicago) to become distinguished judges, lawyers, scientists, and doctors. The direction of this migration was determined in considerable measure by the existence of the Illinois Cen- tral Railroad, which ran from Little Egypt directly to Chi- cago. In other parts of the United States, notably in New En- gland, similar developments have been attributed to parents' erudition and the excellence of educational opportunities. Certainly this explanation does not apply to Little Egypt.
    [Show full text]
  • Novel Treatment Strategies for Glioblastoma
    cancers Editorial Novel Treatment Strategies for Glioblastoma Stanley S. Stylli 1,2 1 Department of Surgery, The University of Melbourne, The Royal Melbourne Hospital, Parkville, VIC 3050, Australia; [email protected] or [email protected] 2 Department of Neurosurgery, The Royal Melbourne Hospital, Parkville, VIC 3050, Australia Received: 22 September 2020; Accepted: 6 October 2020; Published: 8 October 2020 Abstract: Glioblastoma (GBM) is the most common primary central nervous system tumor in adults. It is a highly invasive disease, making it difficult to achieve a complete surgical resection, resulting in poor prognosis with a median survival of 12–15 months after diagnosis, and less than 5% of patients survive more than 5 years. Surgical, instrument technology, diagnostic and radio/chemotherapeutic strategies have slowly evolved over time, but this has not translated into significant increases in patient survival. The current standard of care for GBM patients involving surgery, radiotherapy, and concomitant chemotherapy temozolomide (known as the Stupp protocol), has only provided a modest increase of 2.5 months in median survival, since the landmark publication in 2005. There has been considerable effort in recent years to increase our knowledge of the molecular landscape of GBM through advances in technology such as next-generation sequencing, which has led to the stratification of the disease into several genetic subtypes. Current treatments are far from satisfactory, and studies investigating acquired/inherent resistance to current therapies, restricted drug delivery, inter/intra-tumoral heterogeneity, drug repurposing and a tumor immune-evasive environment have been the focus of intense research over recent years. While the clinical advancement of GBM therapeutics has seen limited progression compared to other cancers, developments in novel treatment strategies that are being investigated are displaying encouraging signs for combating this disease.
    [Show full text]
  • PATIENT H.M.: a Story of Memory, Madness, and Family Secrets” Luke Dittrich (2016), Random House, New York, NY (2016)
    500 Book Reviews criteria) is utilized. This may cause confusion for the reader and lead to discrepant classification of traumatic brain injury severity when examining objective injury severity characteristics. The cerebrovascular disease chapter provides a good description of the etiology of strokes most frequently encountered, but there is little description of stroke syndromes or their associated neuroanatomical locations. The brain tumor chapter would have been enhanced by including a discussion of most common chemotherapy agents and potential benefits and side effects, and the hypoxia/anoxia chapter could have been im- proved by including information about management in the post-acute stages. The ABI secondary to substance use disorders chapter was vague and could have been improved by providing a more in-depth discussion about the potential confounding factors when attempting to draw links between acquired brain injuries and substance use disorders. For example, it is well documented that cigarette smoking and using cocaine increase risk for stroke, but is this a direct link or are those disorders among a number of “vascular risk factors” that cumulatively increase risk for stroke? The addition of chapters about ABI in children and the elderly is a nice supplement to the discussion of numerous clinical syndromes, but entire books can be writ- ten about ABI in these patient populations, which resulted in chapters that read as a bit indistinct. Inclusion of a chapter dedicated to feigning in the context of ABI is certainly appropriate, but the title was a bit misleading Downloaded from https://academic.oup.com/acn/article/32/4/501/3760218 by guest on 03 May 2021 and as with the pediatric or geriatric brain injury literature, the issue of validity is large enough to warrant an entire volume.
    [Show full text]