DOCSLIB.ORG

Carcinogenesis and Chemotherapy—Cancer's Continuing Core Challenges: Third Charles Heidelberger Symposium1

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text

Load more

(CANCER RESEARCH 50. 7405-7409. November 15. 1990) Meeting Report Carcinogenesis and Chemotherapy—Cancer's Continuing Core Challenges: Third Charles Heidelberger Symposium1 Dr. Charles Heidelberger (1920-1983) devoted his entire delberger was able to attend the symposium and to share working life to cancer research and made outstanding contri memories of Charlie with us. butions in the areas of cancer chemotherapy and chemical carcinogenesis. According to his words (1), these parallel threads of research are "cancer's continuing core challenges." Keynote Lecture Dr. Heidelberger was a pioneer in the development of antime- The program of 38 scientific presentations was commenced tabolic drugs for the treatment of cancer. He introduced a with a keynote lecture given by Dr. T. Sugimura (National fluorine atom into uracil to produce 5-FU,2 a standard com Cancer Center, Tokyo, Japan) on "multiple genetic alterations during carcinogenesis." Dr. Sugimura summarized the multiple ponent of long standing, used in several protocols for the treatment of human solid cancers. His contributions to chemi genetic alterations observed in human cancers, which include cal carcinogenesis include the synthesis of radioactive polycyclic point mutations, rearrangements, sequence deletions, gene am aromatic hydrocarbons in the 1940s, the binding of polycyclic plification, and integration of viral genomes. Through these alterations, activation of oncogenes and inactivation of antion- aromatic hydrocarbons to cellular macromolecules in the 1950s cogenes occur, resulting in the acquisition of malignant phe- and 1960s, and the development of mammalian cell transfor mation in vitro in the C3H/10T'/2 cell line in the 1960s and notypes. Multiple genetic alterations are commonly found in many cancers, but the patterns of alterations vary depending 1970s. on origins and histological types of the cancers, with some The symposium held at the International Conference Hall, specificities being observed. Kyoto, Japan, from December 10 to 13, 1989, was the third commemorating Charles Heidelberger's contributions to cancer research. It followed on the success of two previous symposia Session 1: Cell Differentiation organized by his former postdoctoral fellows. The first, on the Dr. Y. Nagai (University of Tokyo, Tokyo, Japan) reported role of chemicals and radiation in the etiology of cancer, was on the significance of "B-pathway" gangliosides in the regula organized by Dr. E. Huberman (Argonne National Laboratory', tion of neural cell growth and differentiation. Among B-path Argonne, IL) and was held from August 26 to 29, 1984, in way gangliosides (GD.„GD2,Gmb, GTn,, and Gyu,), GDj and Oakbrook, IL (2). The second, on transformation and differ G0ib are found to increase in association with the proliferation entiation in vitro, was organized by Dr. J. S. Bertram (Cancer of neuronal cells at the embryonic stage and also with active Research Center of Hawaii, University of Hawaii, Honolulu, gliosis. Exogenous Gylb enhances neurite outgrowth of human HI) from February 9 to 12, 1988, in Honolulu, HI (3). The neuroblastoma cell lines. His observation provides evidence purpose of the third symposium, held in Kyoto, was to discuss that GD.Iand GQib of B-pathway gangliosides are of particular in depth the two areas of research initiated and developed by- importance in relation to cell growth and differentiation in Charles Heidelberger, i.e., carcinogenesis and chemotherapy. neural tissue and possibly to its malignancy. The organizing committee' invited speakers from among Dr. Dr. P. A. Jones (University of Southern California, Los Heidelberger's former postdoctoral fellows, colleagues, and Angeles, CA) reported on the relationship between the meth- those who are extending the research he initiated. The sympo ylation and expression of the MyoDl muscle determination gene in C3H/10T'/: cells. The MyoDl gene is more methylated sium was open for a limited number (about 150) of participants. in C3H/10T'/2 cells than in myogenic derivatives. In addition, We were honored by the presence of Her Royal Highness Chulabhorn of Thailand and fortunate that Mrs. Patricia Hei- transformation results in a marked stimulation of the methyl- ation of the determination gene. The abilities of chemical Received 7/2/90; accepted 8/8/90. carcinogens to perturb DNA methylation patterns may there 'This symposium was held in Kyoto. December 10-13, 1989 at the Kyoto fore be important in silencing genes known to elicit the differ International Conference Hall, Kyoto, Japan. The Osaka Foundation for Pro motion of Fundamental Medical Research and Taiho Pharmaceutical Co., Ltd.. entiation of cells. supported its organization locally while travel of United States participants was Dr. E. Huberman (Argonne National Laboratory, Argonne, sponsored by the following organizations: Bristol-Myers Co.. Pharmaceutical Research and Development Division: The Proctor & Gamble Co.. Miami Valley IL) has been studying early biochemical events that cause Laboratories: The Upjohn Co.. Pharmaceutical Research and Development Di alterations in gene expression leading to terminal differentia vision; Sterling Drug. Inc., a subsidiary of Eastman Kodak: The National Institute tion of human promyelocytic leukemia cells, HL-60. He found of Environmental Health Sciences; The Department of Energy, Office of Health and Environmental Research; Argonne National Laboratory/The University of that a number of early events, such as subcellular translocation Chicago; and The University of Texas M. D. Anderson Science Park. and activation of PKC, phosphorylation of proteins, and mod 2The abbreviations used are: 5-FU. 5-fluorouracil; TPA. 12-O-tetradecanoyl- phorbol-13-acetate; PKC. protein kinase C: XP. xeroderma pigmentosum; G- ulation of topoisomerase II activity, may be early steps in the CSF, granulocyte colony-stimulating factor; cDNA, complementary DNA. signal transduction preceding the induction of cell differentia 3Members of the organizing committee were: Toshio Kuroki (University of tion and tumor promotion by phorbol esters. Tokyo, Tokyo, Japan), (the late) Setsuro Fuji! and Tetsuhiko Shirasaka (The Osaka Foundation for Promotion of Fundamental Medical Research, Osaka, Dr. T. Nakamura (Kyusyu University, Fukuoka, Japan) pre Japan). Toshikazu Oki (Bristol-Myers Research Institute, Ltd., Tokyo. Japan), sented data on molecular cloning of hepatocyte growth factor Shigeru Tsukagoshi (Cancer Chemotherapy Center, Japanese Foundation for and its relevance in liver regeneration. This growth factor is a Cancer Research, Tokyo. Japan), Thomas J. Slaga. (M. D. Anderson Cancer Center. Science Park, Smithville, TX), and Eliezer Huberman (Argonne National heterodimer composed of an «-chain(A/r 69,000) and a ß-chain Laboratory, Argonne. IL). (M, 34,000). Both «-and 0-chains are contained in a single 7405 Downloaded from cancerres.aacrjournals.org on September 25, 2021. © 1990 American Association for Cancer Research. MEETING REPORT open reading frame coding a protein with 728 amino acids, ylation in tumor promotion which can be regulated by the from which the mature heterodimer structure is derived by balance of protein kinases and protein phosphatases. proteolytic cleavage. Its mRNA was detected in nonparenchy- Dr. T. Kuroki (University of Tokyo, Tokyo, Japan) described mal cells of injured liver, suggesting paracrine action of hepa- his work on the purification and characterization of target tocyte growth factor. proteins of PKC in tumor promotion systems in vivo and in cell Cadherin-mediated cell adhesion in normal and transformed culture. In mouse skin in vivo and keratinocytes in culture, M, cells was reported by Dr. M. Takeichi (Kyoto University, Kyoto, 34,000 and M, 40,000 proteins (p34 and p40) are phosphory- Japan). Cadherins, a family of transmembrane glycoproteins lated by PKC at the serine residue. p40 was identified as creatine responsible for Ca2+-dependent intercellular adhesion, were phosphokinase B. It was found, also, that papillomas and discovered and cloned by Takeichi and his colleagues. The carcinomas of mouse skin overexpress "secondary" response amino-terminal 113-amino acid region of the extracellular do genes which are induced 4 h or more after TPA treatment (e.g., main of the molecule is important in determining the specific metallothionein, osteopontin, and urokinase), while the early ities. The intracellular domain is anchored to the cytoskeleton. responding nuclear oncogenes in these tumors remain at low The finding that tumor cell lines with greater metastatic activity levels similar to those in normal skin. express smaller amounts of cadherin suggests possible involve Dr. G. T. Bowden (University of Arizona, Tucson, AZ) ment of cadherins in metastasis. reported on differential gene expression in multistage carcino genesis. Using differential and subtractive hybridization of cDNA libraries he was able to identify five cellular genes that Session 2: Tumor Promotion/Gene Expression are overexpressed at different stages of mouse skin carcinogen TPA, an example of phorbol ester tumor promoters, activates esis. One of these genes, called transin or stromelysin encodes PKC and is known to induce expression of the nuclear onco- a secreted, metalloproteinase which may degrade proteins of genes c-fos and c-jun, the products of which cooperate in the the basement membrane and may play a functional role in transcription of many TPA-inducible genes. It is therefore malignant tumor cell invasion. A similar gene, matrix
Recommended publications
  • The Retinoblastoma Tumor-Suppressor Gene, the Exception That Proves the Rule

    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

    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.
  • Tasmanian Devils' Transmissible Cancer

    Tasmanian Devils' Transmissible Cancer

    Tasmanian devils’ transmissible cancer: Izarbe Aísa Marín Genetics Bachelor’s Degree What is the future? Final Project | June 2017 Introduction Devil Facial Tumor Disease 1Why is Tasmanian devils’ cancer incidence so high? 2Introduction to transmissible cancers Carcinogenesis is thought to occur via Peto’s Paradox represents the lack of accumulation of mutations and mutation correlation between cancer prevalence rates depend on cell number, which and body size or lifespan and it can be Primary Mode of Lack of Capacity for correlates with body size and lifespan. useful to explore cases that are far tumor’s origin transmission allorecognition infinite growth Then, large and long-lived animals from what is expected. Tasmanian should have more cancers than smaller devils suffer from Devil Facial Tumor and shorter-lived ones, due to increased Disease (DFTD), a lethal transmissible The ancestral type of DTDF is thought to be derived from a Schwann cell (clonal number of cell divisions. cancer that is threatening the species origin) and it is transmitted by biting during mating or feeding interactions. to extinction. (2) (1) y = 0,0815 - 0,0061x [y=%Tumors; x=Log(Mass[x]*LifeSpan[y])] 10x DFTD was first reported in Mount William National Park, northeastern Tasmania, in 1996. In 20 years, the disease has spread to more than 85% Forestier of wild Tasmanian devil Peninsula populations, causing severe declines. Immunology of DFTD 3Why devils immune system do not recognize DFTD? (3) Deficiency of devil Marsupials’ immune system is different immune system from, rather than inferior to mammals’ immune system. Immunological Low genetic Slower immune responses tolerance diversity facilitate early transmission events.
  • Principles of Cancer Prevention and Will Emphasize the Scientific Underpinnings of This Emerging Discipline

    Principles of Cancer Prevention and Will Emphasize the Scientific Underpinnings of This Emerging Discipline

    Seminars in Oncology Nursing, Vol 21, No 4 (November), 2005: pp 229-235 229 OBJECTIVE: To summarize the scientific prin- ciples underlying cancer preven- tion. PRINCIPLES OF DATA SOURCES: Articles, text books, personal com- CANCER munications, and experience. CONCLUSION: PREVENTION The scientific basis of cancer pre- vention is complex and involves experimental and epidemiologic approaches and clinical trials. FRANK L. MEYSKENS,JR AND PATRICIA TULLY IMPLICATIONS FOR NURSING PRACTICE: ANCER prevention has classically encompassed As more information becomes three large areas of clinical practice: prevention, available regarding proven and screening, and early detection. Several excellent potential cancer-prevention strate- reviews and book chapters have been published gies, oncology nurses are regu- involving these topics.1-3 The importance of bio- larly called upon to guide patients Clogical and molecular markers as potential surrogates have been and others in making choices re- emphasized in the past several years,4,5 and more recently precan- garding preventative options. It is cers or intraepithelial neoplasia (IEN) have become a target.6,7 The important for oncology nurses to integration of the well-established approaches of prevention, stay abreast of this growing body screening, and early detection with biological measures of disease of knowledge. risk, progression, and prognosis has become the hallmark of mod- ern cancer prevention (see Fig 1). In this article we will review the principles of cancer prevention and will emphasize the scientific underpinnings of this emerging discipline. The principles of cancer prevention have evolved from three separate scientific disciplines: carcinogenesis, epidemiology, and clinical trials. Many other areas From the Department of Medicine and of science and medicine, including genetics and the behavioral Biological Chemistry, Chao Family Com- sciences, are contributing to this evolving and complex field.
  • Inhibitors of Mammalian Target of Rapamycin Downregulate MYCN Protein Expression and Inhibit Neuroblastoma Growth in Vitro and in Vivo

    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.
  • 1P36 Tumor Suppression—A Matter of Dosage?

    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).
  • Carcinogenesis

    Carcinogenesis

    Chapter 3 Chapter 3 Carcinogenesis CONTENTS Oral Carcinoma and Smokeless Tobacco Use: A Clinical Profile W. Frederick McGuirt and Anna Wray .................................................. 91 Introduction .................................................................................... 91 Patients ............................................................................................ 91 Field Cancerization ......................................................................... 92 Discussion........................................................................................ 93 References ........................................................................................ 95 Chemical Composition of Smokeless Tobacco Products Klaus D. Brunnemann and Dietrich Hoffmann ..................................... 96 Introduction .................................................................................... 96 Chemical Composition ................................................................... 97 Carcinogenic Agents in ST .............................................................. 97 Carcinogenic N-Nitrosamines ....................................................... 100 TSNA .............................................................................................. 101 Control of Carcinogens in ST ....................................................... 104 References ...................................................................................... 106 Carcinogenesis of Smokeless Tobacco Dietrich Hoffmann, Abraham
  • Mitochondrial Metabolism in Carcinogenesis and Cancer Therapy

    Mitochondrial Metabolism in Carcinogenesis and Cancer Therapy

    cancers Review Mitochondrial Metabolism in Carcinogenesis and Cancer Therapy Hadia Moindjie 1,2, Sylvie Rodrigues-Ferreira 1,2,3 and Clara Nahmias 1,2,* 1 Inserm, Institut Gustave Roussy, UMR981 Biomarqueurs Prédictifs et Nouvelles Stratégies Thérapeutiques en Oncologie, 94800 Villejuif, France; [email protected] (H.M.); [email protected] (S.R.-F.) 2 LabEx LERMIT, Université Paris-Saclay, 92296 Châtenay-Malabry, France 3 Inovarion SAS, 75005 Paris, France * Correspondence: [email protected]; Tel.: +33-142-113-885 Simple Summary: Reprogramming metabolism is a hallmark of cancer. Warburg’s effect, defined as increased aerobic glycolysis at the expense of mitochondrial respiration in cancer cells, opened new avenues of research in the field of cancer. Later findings, however, have revealed that mitochondria remain functional and that they actively contribute to metabolic plasticity of cancer cells. Understand- ing the mechanisms by which mitochondrial metabolism controls tumor initiation and progression is necessary to better characterize the onset of carcinogenesis. These studies may ultimately lead to the design of novel anti-cancer strategies targeting mitochondrial functions. Abstract: Carcinogenesis is a multi-step process that refers to transformation of a normal cell into a tumoral neoplastic cell. The mechanisms that promote tumor initiation, promotion and progression are varied, complex and remain to be understood. Studies have highlighted the involvement of onco- genic mutations, genomic instability and epigenetic alterations as well as metabolic reprogramming, Citation: Moindjie, H.; in different processes of oncogenesis. However, the underlying mechanisms still have to be clarified. Rodrigues-Ferreira, S.; Nahmias, C. Mitochondria are central organelles at the crossroad of various energetic metabolisms.
  • Cancer Biology Introduction Proto-Oncogenes Tumor

    Cancer Biology Introduction Proto-Oncogenes Tumor

    Introduction • Tissue homeostasis depends on the regulated cell division and self-elimination (programmed cell Cancer Biology death) of each of its constituent members except its stem cells • A tumor arises as a result of uncontrolled cell division and failure for self-elimination Chapter 18 • Alterations in three groups of genes are responsible Eric J. Hall., Amato Giaccia, for the deregulated control mechanisms that are the hallmarks of cancer cells: proto-oncogenes, tumor- Radiobiology for the Radiologist supressor genes, and DNA stability genes Proto-oncogenes Tumor-suppressor genes • Proto-oncogenes are components of signaling • Tumor-suppressor genes are also components of networks that act as positive growth the same signaling networks as proto-oncogenes, except that they act as negative growth regulators regulators in response to mitogens, cytokines, • They modulate proliferation and survival by and cell-to-cell contact antagonizing the biochemical functions of proto- • A gain-of-function mutation in only one copy oncogenes or responding to unchecked growth signals of a protooncogene results in a dominantly • In contrast to oncogenes, inactivation of both acting oncogene that often fails to respond to copies of tumor-suppressor genes is required for extracellular signals loss of function in most cases DNA stability genes Mechanisms of carcinogenesis • DNA stability genes form a class of genes • A single genetic alteration that leads to the involved in both monitoring and activation of an oncogene or loss of a tumor maintaining
  • Retinoblastoma

    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
  • A Guide to Cancer Immunotherapy: from T Cell Basic Science to Clinical Practice

    A Guide to Cancer Immunotherapy: from T Cell Basic Science to Clinical Practice

    REVIEWS A guide to cancer immunotherapy: from T cell basic science to clinical practice Alex D. Waldman 1,2, Jill M. Fritz1,2 and Michael J. Lenardo 1,2 ✉ Abstract | The T lymphocyte, especially its capacity for antigen-directed cytotoxicity, has become a central focus for engaging the immune system in the fight against cancer. Basic science discoveries elucidating the molecular and cellular biology of the T cell have led to new strategies in this fight, including checkpoint blockade, adoptive cellular therapy and cancer vaccinology. This area of immunological research has been highly active for the past 50 years and is now enjoying unprecedented bench-to-bedside clinical success. Here, we provide a comprehensive historical and biological perspective regarding the advent and clinical implementation of cancer immunotherapeutics, with an emphasis on the fundamental importance of T lymphocyte regulation. We highlight clinical trials that demonstrate therapeutic efficacy and toxicities associated with each class of drug. Finally, we summarize emerging therapies and emphasize the yet to be elucidated questions and future promise within the field of cancer immunotherapy. Neoantigens The idea to deploy the immune system as a tool to treat system to prevent carcinogenesis in a manner similar to 1 1 Antigens not expressed by neoplastic disease originated in the nineteenth century . graft rejection . Productive immune responses following self-tissues under normal Wilhelm Busch and Friedrich Fehleisen were the first tumoural adoptive transfer in mice4 and clinical reports conditions that manifest in to describe an epidemiological association between of spontaneous regression of melanoma in patients with the context of pathology; in 5 cancer, these could be altered immune status and cancer.
  • The Functional Loss of the Retinoblastoma Tumour Suppressor

    The Functional Loss of the Retinoblastoma Tumour Suppressor

    Available online http://breast-cancer-research.com/content/10/5/R75 ResearchVol 10 No 5 article Open Access The functional loss of the retinoblastoma tumour suppressor is a common event in basal-like and luminal B breast carcinomas Jason I Herschkowitz1,2,4, Xiaping He1,2, Cheng Fan1 and Charles M Perou1,2,3 1Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC 27599, USA 2Department of Genetics, University of North Carolina, Chapel Hill, NC 27599, USA 3Department of Pathology & Laboratory Medicine, University of North Carolina, Chapel Hill, NC 27599, USA 4Department of Molecular and Cellular Biology, Baylor College of Medicine, One Baylor Plaza, DeBakey M635, Houston, TX 77030, USA Corresponding author: Charles M Perou, [email protected] Received: 19 Jun 2008 Revisions requested: 31 Jul 2008 Revisions received: 22 Aug 2008 Accepted: 9 Sep 2008 Published: 9 Sep 2008 Breast Cancer Research 2008, 10:R75 (doi:10.1186/bcr2142) This article is online at: http://breast-cancer-research.com/content/10/5/R75 © 2008 Herschkowitz et al.; licensee BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Abstract Introduction Breast cancers can be classified using whole Results RB1 loss of heterozygosity was observed at an overall genome expression into distinct subtypes that show differences frequency of 39%, with a high frequency in basal-like (72%) and in prognosis. One of these groups, the basal-like subtype, is luminal B (62%) tumours.