DOCSLIB.ORG

DJ-1 Could Predict Worse Prognosis in Esophageal Squamous Cell Carcinoma

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
DJ-1 Could Predict Worse Prognosis in Esophageal Squamous Cell Carcinoma 3593 DJ-1 Could Predict Worse Prognosis in Esophageal Squamous Cell Carcinoma Hiu-Fung Yuen,1,3 Yuen-Piu Chan,1 Simon Law,2 Gopesh Srivastava,1 Mohamed El-tanani,3 Tak-Wah Mak,4,5 and Kwok-Wah Chan1 Departments of 1Pathology and 2Surgery, The University of Hong Kong, Hong Kong, People’s Republicof China; 3Centre for Cancer Research and Cell Biology, Queen’s University of Belfast, Belfast, United Kingdom; and 4Advanced Medical Discovery Institute, The Campbell Family Institute for Breast Cancer Research, Ontario Cancer Institute; 5Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada Abstract Recent studies have revealed an oncogenic role of DJ-1 promotes ESCC progression through phosphatidylino- through its ability to transform normal cells, prevent sitol3-kinase pathway and modulationof apoptosis, oxidative damage, and inhibit apoptosis. However, we performed immunohistochemistry of pAkt and its role in esophageal squamous cell carcinoma (ESCC) Daxx. We found that DJ-1 expression was significantly is unknown. In this study, by immunohistochemistry, associated with pAkt, whereas nuclear DJ-1 expression we analyzed the expression of DJ-1 in 81 ESCC tumors, was significantly correlated with nuclear expression 31 paired nonneoplastic esophageal epithelia, and 19 of Daxx. These results suggest that phosphatidyli- paired ESCC lymph node metastases. We found nositol3-kinase pathway and Daxx-regulatedapoptosis that cytoplasmic DJ-1 expression was significantly might be important in DJ-1-mediated ESCC progres- higher in ESCC and ESCC lymph node metastases sion. By using multivariate Cox regression, we fur- P than in nonneoplastic esophageal epithelium. ESCC ther showed that T4 stage ( =0.003)andDJ-1 specimens with high distant metastatic potentialalso (P = 0.034) are independent predictors of patient had a significantly higher level of nuclear DJ-1 survival. In conclusion, our results suggest that DJ-1 expression (P = 0.018). By Kaplan-Meier analysis, plays a very important role in transformation and we found that a high level of nuclear DJ-1 was sig- progression of ESCC and may be used as a prognostic nificantly associated with poorer patient survival in marker in ESCC. (Cancer Epidemiol Biomarkers Prev our cohort (P = 0.028). To investigate whether DJ-1 2008;17(12):3593–602) Introduction Esophageal squamous cell carcinoma (ESCC) is common for its antiapoptoticand transformation ability (5), among Asian populations. Despite recent advances in whereas DJ-1 also interacts with and inhibits the func- the detection of premalignant lesions and the develop- tion of Daxx, which binds to apoptosis signal-regulating ment of combination therapies, its incidence is increas- kinase 1 to promote apoptosis induced by oxidative ing and its outcome remains poor (1). Proper clinical stress (6). The antioxidative activity of DJ-1 also links to management should be given to patients with aggres- the ability of DJ-1 to induce Nrf2 stability, which in turn sive ESCC, which might improve survival. Identification activates the transcription of antioxidant and detoxifi- of prognosticmarkers for ESCC might help to make the cation enzymes (7). In another study, DJ-1 has been decision on which treatment regimen is the most suitable shown to up-regulate glutathione synthesis, which is a for a patient in terms of quality of living. downstream target of Nrf2, to protect cells from oxida- DJ-1 has been identified as an oncogene that can tran- tive stress-induced apoptosis (8). More recently, DJ-1 sform mouse NIH3T3 cells together with ras (2). Its has been shown to decrease the expression of Bax and oncogenic effect is partly attributed to its antiapoptotic inhibit caspase activation, suggesting a direct role of ability. DJ-1 is an important factor governing apoptotic DJ-1 in inhibiting the apoptotic pathway (9). In cancer response in neuronal cells. It has been shown to pro- cells, decreased expression of DJ-1 enhances apoptosis tect neuronal apoptosis, whereas decreased expression in prostate (10) and lung cancer cells (9, 11). These lines of DJ-1 increases apoptosis of neuronal cells to various of evidence suggest that DJ-1 is important in regulat- stresses (3, 4). Recent functional studies on DJ-1 revealed ing apoptosis and hence plays an important role in several important mechanisms on how it inhibits apop- carcinogenesis. tosis. Sumoylation of the K130 residue of DJ-1 is essential The roles and prognostic significance of DJ-1 have been studied in certain types of cancer. In breast cancer patients, serum level of DJ-1 is increased when compared Received 3/10/08; revised 8/4/08; accepted 9/5/08. with healthy subjects (12). DJ-1 negatively correlates with Note: Supplementary data for this article are available at Cancer Epidemiology the expression of a potent tumor suppressor, PTEN, in Biomarkers and Prevention Online (http://cebp.aacrjournals.org/). human breast cancer specimens (13). DJ-1 is increased in Requests for reprints: Kwok-Wah Chan, Department of Pathology, Queen Mary primary lung cancer (11) and a high level of DJ-1 is Hospital, Hong Kong, People’s Republicof China. Phone: 852-28554874; Fax: 852-28725197. E-mail: [email protected] correlated with poor prognosis of lung cancer patients Copyright D 2008 American Association for Cancer Research. (13). Reduced DJ-1 sensitizes prostate cancer cells toward doi:10.1158/1055-9965.EPI-08-0214 apoptotic-inducing agents (10). DJ-1 has been shown to Cancer Epidemiol Biomarkers Prev 2008;17(12). December 2008 Downloaded from cebp.aacrjournals.org on October 5, 2021. © 2008 American Association for Cancer Research. 3594 DJ-1 in Esophageal Squamous Cell Carcinoma be an androgen receptor coactivator (14), which interacts Table 1. Patient clinical and pathologic features with androgen receptor, and is up-regulated in human No. (%) Median prostate cancer on androgen deprivation therapy (15). cases (range) These results strongly suggest that DJ-1 promotes prostate cancer progression. Recently, DJ-1 has also been Age (y) 81 67 (41-87) suggested to confer prognostic value to ovarian carcino- Sex ma with effusions (16). Male 62 (77) Female 19 (24) There has not been any report concerning the T stage significance of DJ-1 in ESCC. In this study, we analyzed, T1 2 (3) by immunohistochemistry, the expression of DJ-1 in 81 T2 13 (16) ESCC specimens with 31 paired nonneoplastic esopha- T3 49 (61) geal epithelium and 19 paired ESCC lymph node T4 17 (21) N stage metastasis. The expression of DJ-1 was then correlated N 30 (37) with the clinicopathologic data of the patients. In 0 N1 51 (63) addition, as DJ-1 has been shown to promote cell sur- M stage vival through the phosphatidylinositol 3-kinase (PI3K) M0 68 (84) pathway by modulating PTEN and Akt activity (13, 17) M1 13 (16) and apoptoticresponse through Daxx (6), we further pTNM staging Stage II 32 (40) investigated the association between DJ-1 and pAkt or Stage III 36 (44) Daxx in the ESCC tumor specimens. Stage IV 13 (16) Histologicgrade Well-differentiated 13 (16) Materials and Methods Moderately differentiated 48 (59) Poorly differentiated 20 (25) Patients and Specimens. Our cohort consists of 81 Metastaticstatus Nonmetastatic55 (68) ESCC Chinese patients who underwent total esophagec- Metastatic(within 1 y) 26 (32) tomy for ESCC in Queen Mary Hospital from 1998 to 2005. The esophagectomy specimens were formalin-fixed and paraffin-embedded for routine histopathologicdi- night at 4jC. pAkt (Ser473) antibody from Cell Signaling agnosis. The specimens were collected consecutively. and Daxx antibody from Upstate were applied at a Patients who had received prior treatment directed dilution of 1:50 and 1:100, respectively, for overnight against ESCC or specimens with insufficient tumor tis- at 4jC. The primary antibody was omitted in the nega- sue for microarray incorporation or subsequent immu- tive control. nohistochemical study were excluded from this study. The extent of tumor at the time of operation was class- Evaluation of Immunohistochemical Staining ified according to the tumor-node-metastasis (TNM) Results. The stained sections were reviewed by two staging system, whereas tumor grades were classified independent observers (K.W.C. and Y.P.C.) who had no based on the WHO classification (18). The clinical data prior knowledge of the clinicopathologic data of the were retrieved and are summarized in Table 1. Adjuvant patients. All three cores of each specimen were scored therapies were given to the patient in a ‘‘curative intent’’ and the ‘‘hot spot’’ core was selected for later statistical manner despite the heterogeneity of the treatment. analysis. Cytoplasmicstaining was graded by an Paired nonneoplasticesophageal epithelium was selected arbitrary scale based on the extent and the intensity of from the upper resection margin of esophagectomy for the whole tissue core. A cytoplasmic staining score was comparison with tumor. The ESCC tumors were given, ranging from 0 to 3, which represent negative, regarded as having a high distant metastaticpotential if weak, moderate, and strong staining, respectively. For distant metastasis could be detected within 1 year of nuclear staining, nuclei from the whole tissue core esophagectomy, else they were considered to have a low were counted and only those cores with >100 nuclei of distant metastaticpotential. The mean follow-up time of target cells were submitted for statistical analysis. The our patients is 14.5 months (range, 0.7-65.2 months). DJ-1 nuclear score was then divided into four groups according to the percentage of cells positively stained as Tissue Microarray Construction. Tissue microarray negative (V5% nuclear stained positive), weak (>5% and (TMA) was constructed with a Beecher Instruments V20%), moderate (20% and V50%), and strong (z50%). tissue microarrayer as described previously (19). Briefly, For pAkt and Daxx, their nuclear score was respectively three representative areas of each specimen were selected graded into four groups as negative (V5% nuclear stained by a pathologist (K.W.C.) and transferred to a TMA block positive), weak (>5% and V20%), moderate (20% and using a 0.6 mm core diameter needle.
Load more

Recommended publications
  • Medical Immunology Campus Erlangen
    INTERDISCIPLINARY CENTERS AND CENTRAL INSTITUTES Medical Immunology Campus Erlangen Speaker in its first phase will be funded by the DFG from 10.1.2017 Prof. A. Alimonti, Institute of Oncology Re- Prof. Dr. med. Christian Bogdan Juli 2018 until June 2022 (TRR 241 „Immune-ep- search, Bellinzona: Switzerland Reprogramming the tumor immune response for „pro- ithelial communication in inflammatory bowel senescence“ therapy for cancer Scientific coordinator disease“, compareown report). In addition, we 30.5.2017 Prof. A. Zippelius, Department of Biomedicine, Dr. rer. nat. Sonja Pötzsch hope for the approval of the GK 2504/1 „Novel University Hospital Basel: Switzerland antiviral approaches: From small molecules to im- Cancer Immunotherapy: Strategies for personalization and combination approaches Address mune intervention“ (designated speaker: Prof. Dr. Institute of Clinical Microbiology, K. Überla), which was positively evaluated in De- 13.6.2017 PD Dr. S. Autenrieth, university hospital Tübin- gen Immunology and Hygiene cember 2018, as well as for the success of two Modulation of dendritic cells by bacterial pathogens Wasserturmstraße 3-5 further GK initiatives, which are currently in the 17.10.2017 Prof. M. Sieweke, Centre d’Immunologie de 91054 Erlangen stage of preparing the full proposal (GK 2559/1 Marseille Luminy: France Phone: +49 9131 8522571 „Immunomicrotope: Microenvironmental, meta- Stem cell like mechanisms of macrophage self renewal Fax: +49 9131 8522573 bolic, and microbial signals regulating immune 7.11.2017 Prof. D. Finke, Universitäts-Kinderspital Basel: [email protected] cell-pathogen interventions“, designated speaker: Switzerland License to operate - new insights into the regulation of ILC www.mice.fau.de Prof.
    [Show full text]
  • Bulletin Vol
    american academy of arts & sciences winter 2006 Bulletin vol. lix, no. 2 Page 1 American Academy Welcomes the 225th Class of Members Page 2 Exhibit from the Archives Members’ Letters of Acceptance Page 26 Concepts of Justice Essays by Alan Brinkley, Kathleen M. Sullivan, Geoffrey Stone, Patricia M. Wald, Charles Fried, and Kim Lane Scheppele inside: Projects and Studies, Page 15 Visiting Scholars Program, Page 24 New Members: Class of 2005, Page 42 From the Archives, Page 60 Calendar of Events Thursday, Saturday, February 9, 2006 March 18, 2006 Stated Meeting–Cambridge Stated Meeting–San Francisco “Tax Reform: Current Problems, Possible “Innovation: The Creative Blending of Art Contents Solutions, and Unresolved Questions” and Science” Speaker: James Poterba, mit Speaker: George Lucas, Lucas½lm Ltd. Academy News Introduction and Response: Michael J. Introduction: F. Warren Hellman, Graetz, Yale University Hellman & Friedman, LLC Academy Inducts 225th Class 1 Location: House of the Academy Location: Letterman Digital Arts Center, The Presidio of San Francisco Major Funding from the Mellon Time: 6:00 p.m. Foundation 1 Time: 5:00 p.m. Exhibit from the Academy’s Archives 2 Wednesday, February 15, 2006 Tuesday, April 4, 2006 Challenges Facing the Regional Meeting–Chicago Intellectual Community 7 Stated Meeting and Joint Meeting with “America’s Greatest Lawyer: Abraham Lincoln the Boston Athenæum–Boston in Private Practice and Public Life” Projects and Studies 15 “Great Scienti½c Discoveries of the Twentieth Speaker: Walter E. Dellinger, Century” Duke University Visiting Scholars Program 24 Speaker: Alan Lightman, mit Introduction: Saul Levmore, Academy Lectures University of Chicago Law School Location: Boston Athenæum Location: University of Chicago Law School Time: 6:00 p.m.
    [Show full text]
  • Retreat 2009
    Ninth Annual CCR Fellows and Young Investigators Colloquium Program Wednesday, March 18, 2009 2:00 p.m. Registration and Mentored Dinner Sign-up (Great Lobby) Poster Session I Setup (Red Room) 3:00 p.m. Plenary Session I (White Room) Moderators: Tim Chan, Ph.D. and Edward Wright, Ph.D. Opening Remarks and CCR-FYI Overview Tim Chan, Ph.D., Chair, CCR FYI Steering Committee Felcom Overview Thomas Paul, Ph.D., Laboratory of Cellular Oncology, CCR, NCI Update on the National Postdoctoral Association Stacy Gelhaus, Ph.D., University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 3:45 p.m. Opening Remarks from the CCR Office of Training and Education Jonathan Wiest, Ph.D., Associate Director, Office of Training and Education, CCR, NCI 4.00 p.m. CCR Office of the Director Address Robert Wiltrout, Ph.D., Director, Center for Cancer Research, NCI 4:30 p.m. Keynote Speaker I: “Insights from a New Lung Cancer Stem Cell Assay” (White Room) Carla Kim, PhD., Assistant Professor, Department of Genetics, Harvard Medical School Moderators: Bríd Ryan, Ph.D., M.P.H. and Paul Hynes, Ph.D. 5:30 p.m. Mentored and General Dinner (Nigerian Room) 7:00 p.m. Keynote Speaker II: “Cancer Metabolism: Back to the Future” (White Room) Tak Wah Mak, Ph.D., Director, The Campbell Family Institute for Breast Cancer Research, Princess Margaret Hospital, University of Toronto, Ontario, Canada Moderators: Tim Chan, Ph.D. and Ram Savan, Ph.D. 8:00 p.m. Highlight Presentation: “DEAR TALULA: An Intimate Portrait of a Cancer Survivor” Lori Benson, Breast Cancer Survivor 8:30 p.m.
    [Show full text]
  • Laurentian University Université Laurentienne May 29, 2018 - 10 A.M
    Laurentian University Université Laurentienne May 29, 2018 - 10 a.m. Procession The audience will rise when the academic procession enters the auditorium. Invocation Hand-drummer – Rob Spade The audience will be seated. Address to Graduands and Guests Dr. Pierre Zundel, Interim President and Vice-Chancellor, Laurentian University Conferring of the Honorary Degree Ms. Hélène Dallaire and Dr. Jean-Charles Cachon will present Nicole Boivin, for the Doctorate of Laws (honoris causa). Dr. Boivin will address Convocation. Conferring of Degrees in Course The graduating classes will be presented to the Chancellor, and Interim President and Vice-Chancellor. Dean Stephen Havlovic will present the candidates to the degrees in the Faculty of Management. Proclamation of Degrees and Diplomas Mr. Steve Paikin, Chancellor, Laurentian University Presentation of Professor Emeritus Dr. Serge Demers, Interim Vice-President, Academic and Provost, will present one of the university’s newly named Professor Emeritus, Dr. Ozhand Ganjavi. Welcome to Graduates Mr. Jean-Paul Rains, SPAD 2009, MBA 2015, Laurentian University Alumni Association Announcements Dr. Pierre Zundel, Interim President and Vice-Chancellor, Laurentian University National Anthem O Canada The audience will rise to sing O Canada and will remain standing until the procession has departed. Closing Dr. Pierre Zundel, Interim President and Vice-Chancellor, Laurentian University “Convocatio dimissa est.” The graduates and guests are invited to a reception in Alumni Hall immediately following the convocation ceremony. Recession Music The Allan Walsh Trio: Allan Walsh - saxophone, Brian Quebec - bass, Ron Kelly - guitar Le 29 mai 2018 - 10 h Entrée du cortège L’assistance se lève. Invocation Joueur de tambour – Rob Spade L’assistance s’asseoit.
    [Show full text]
  • Convocation Booklet
    Laurentian University Université Laurentienne October 28, 2017 - Morning Ceremony Procession The audience will rise when the academic procession enters the auditorium. Invocation Hand-Drummer – Brandon Petahtegoose The audience will be seated. Address to Graduands and Guests Dr. Pierre Zundel, Interim President and Vice-Chancellor Conferring of Degrees in Course The graduating classes will be presented to the Chancellor, and Interim President and Vice-Chancellor. Dean Elizabeth Dawes will present the candidates to the degrees in the Faculty of Arts. Interim Dean Céline Larivière will present the candidates to the degrees in the Faculty of Health. Dean David Lesbarrères will present the candidates to the degrees in the Faculty of Graduate Studies. Proclamation of Degrees and Diplomas Mr. Steve Paikin, Chancellor Welcome to the New Graduates Mr. Guy Robineau BA 2007, MBA 2013, Laurentian University Alumni Association Announcements Dr. Pierre Zundel, Interim President and Vice-Chancellor National Anthem O Canada The audience will rise to sing O Canada and will remain standing until the procession has departed. Closing Dr. Pierre Zundel, Interim President and Vice-Chancellor “Convocatio dimissa est.” The graduates and guests are invited to a reception in Alumni Hall immediately following the convocation ceremony. Recession Music The Allan Walsh Trio: Allan Walsh - saxophone, Brian Quebec - bass, Ron Kelly - guitar Le 28 octobre 2017 - Cérémonie du matin Entrée du cortège L’assistance se lève. Invocation Joueur de tambour – Brandon Petahtegoose L’assistance s’asseoit. Allocution aux classes finissantes et aux invités M. Pierre Zundel, recteur et vice-chancelier par intérim Collation des grades universitaires Les classes finissantes sont présentées au chancelier, et au recteur et vice-chancelier par intérim.
    [Show full text]
  • Proud and Strong 2017 and Beyond
    Proud and Strong 2017 and Beyond Rosie MacLennan Olympic Trampoline Gymnast Identity & Citizenship Gordon Pinsent 2 Film Director, Actor, Poet, Playwright Identity & Citizenship The Canadian Icons Project / Canadian Change Conversations celebrate our identity and citizenship. Launched in conjunction with Canada’s 150th Anniversary, these initiatives create a place and space, physical and virtual, for conversations about issues that are shaping our society today and tomorrow. The goal is to reflect on our achievements – but also to deepen engagement, inspire positive action, and promote change and innovation that make our communities and nation even stronger and more sustainable. 63 Identity & Citizenship The Canadian Icons Project is a photographic and multimedia showcase of 150 iconic Canadians whose contributions have been felt across Canada and around the world, and who chronicle our nation’s diversity, creativity and achievements. The Canadian Change Conversations creates a platform to engage the Icons and Canadians at large in a series of narratives and demonstration projects designed to inform, challenge and change how we see our communities, our nation, our world and ourselves. Harnessing the power of Canadian Icons who serve to inspire, motivate and lead social change; exploring voices of citizens who help shape and move our communities; and supporting experimental 'makerspaces' to demonstrate responses and potential, the Canadian Icons Project / Canadian Change Conversations together encourage critical conversations designed to activate citizenship aimed at positive social change and innovation. 64 Don Dixon Creator, Director & Photographer of the Canadian Icons Project "Five years ago, with the help of some of Canada’s most talented communications and media industry experts, I began my journey – to photograph and interview Canada’s most accomplished living icons, in celebration of Canada's Sesquicentennial.
    [Show full text]
  • Keratinocyte-Specific Pten Deficiency Results in Epidermal Hyperplasia, Accelerated Hair Follicle Morphogenesis and Tumor Formation1
    [CANCER RESEARCH 63, 674–681, February 1, 2003] Keratinocyte-specific Pten Deficiency Results in Epidermal Hyperplasia, Accelerated Hair Follicle Morphogenesis and Tumor Formation1 Akira Suzuki, Satoshi Itami,2 Minako Ohishi,2 Koichi Hamada, Tae Inoue, Nobuyasu Komazawa, Haruki Senoo, Takehiko Sasaki, Junji Takeda, Motomu Manabe, Tak Wah Mak,3, 4 and Toru Nakano3, 5 Departments of Biochemistry [A. S., K. H.], Dermatology [T. I., M. M.], and Anatomy [H. S.], Akita University School of Medicine, Akita 010-8543, Japan; Department of Molecular Cell Biology, Research Institute for Microbial Disease [M. O., T. N.], Department of Dermatology [S. I.], and Department of Social and Environmental Medicine [N. K., J. T.], Graduate School of Medicine, Osaka University, Osaka 565-0871, Japan; Department of Pharmacology, Tokyo Metropolitan Institute of Medical Science, Tokyo 113-8613, Japan [T. S.]; and Advanced Medical Discovery Institute, University of Toronto, Toronto, Ontario, M5G 2C1 Canada [T. W. M.] ABSTRACT The epidermis of the skin is a keratinized and stratified squamous epithelium composed mainly of keratinocytes, cells whose prolifera- PTEN is a tumor suppressor gene mutated in many human cancers. We tion and differentiation must be tightly regulated and coordinated used the Cre-loxP system to generate a keratinocyte-specific null mutation (13–15). Keratinocytes first attach to the basal membrane of the of Pten in mice (k5Ptenflox/flox mice). k5Ptenflox/flox mice exhibit wrinkled skin because of epidermal hyperplasia and hyperkeratosis and ruffled, epidermis as undifferentiated precursor cells. These precursors mi- shaggy, and curly hair. Histological examination revealed that skin mor- grate toward the surface of the epidermis and subsequently form its phogenesis is accelerated in k5Ptenflox/flox mice.
    [Show full text]
  • Printable List of Laureates
    Laureates of the Canadian Medical Hall of Fame A E Maude Abbott MD* (1994) Connie J. Eaves PhD (2019) Albert Aguayo MD(2011) John Evans MD* (2000) Oswald Avery MD (2004) F B Ray Farquharson MD* (1998) Elizabeth Bagshaw MD* (2007) Hon. Sylvia Fedoruk MA* (2009) Sir Frederick Banting MD* (1994) William Feindel MD PhD* (2003) Henry Barnett MD* (1995) B. Brett Finlay PhD (2018) Murray Barr MD* (1998) C. Miller Fisher MD* (1998) Charles Beer PhD* (1997) James FitzGerald MD PhD* (2004) Bernard Belleau PhD* (2000) Claude Fortier MD* (1998) Philip B. Berger MD (2018) Terry Fox* (2012) Michel G. Bergeron MD (2017) Armand Frappier MD* (2012) Alan Bernstein PhD (2015) Clarke Fraser MD PhD* (2012) Charles H. Best MD PhD* (1994) Henry Friesen MD (2001) Norman Bethune MD* (1998) John Bienenstock MD (2011) G Wilfred G. Bigelow MD* (1997) William Gallie MD* (2001) Michael Bliss PhD* (2016) Jacques Genest MD* (1994) Roberta Bondar MD PhD (1998) Gustave Gingras MD* (1998) John Bradley MD* (2001) Phil Gold MD PhD (2010) Henri Breault MD* (1997) Richard G. Goldbloom MD (2017) G. Malcolm Brown PhD* (2000) Jean Gray MD (2020) John Symonds Lyon Browne MD PhD* (1994) Wilfred Grenfell MD* (1997) Alan Burton PhD* (2010) Gordon Guyatt MD (2016) C H G. Brock Chisholm MD (2019) Vladimir Hachinski MD (2018) Harvey Max Chochnov, MD PhD (2020) Antoine Hakim MD PhD (2013) Bruce Chown MD* (1995) Justice Emmett Hall* (2017) Michel Chrétien MD (2017) Judith G. Hall MD (2015) William A. Cochrane MD* (2010) Michael R. Hayden MD PhD (2017) May Cohen MD (2016) Donald O.
    [Show full text]
  • Annual Report 2016 the UNIVERSITYTHE UNIVERSITY of TEXAS of TEXAS SYSTEM SYSTEM BOARD BOARD of REGENTS of REGENTS
    patient care The University of Texas MD Anderson Cancer Center MD Anderson of Texas The University research prevention education global outreach cytogenetic technology neuroscience experimental therapeutics biochemistry molecular biology annual report 75 years of genetics genetic counseling patient care palliative care cancer epigenetics research translational research prevention genomics stem cell transplantation education clinical and translational research making cancer history proton therapy molecular carcinogenesis gene expression research germline mutagenesis health disparities research nanomedicine p53 drug development chromatin remodelers nanotechnology integrative medicine cancer care innovation survivorship Annual Report 2016 clinical trials THE UNIVERSITYTHE UNIVERSITY OF TEXAS OF TEXAS SYSTEM SYSTEM BOARD BOARD OF REGENTS OF REGENTS ® ® Paul L.Paul Foster, L. Foster, El Paso El Paso ChairmanChairman In honorIn honor of Charlesof Charles Aubrey Aubrey “Mickey” “Mickey” LeMaistre, LeMaistre, M.D. M.D. 7575 years years of of Making Making Cancer Cancer History History R. StevenR. Steven Hicks, Hicks, Austin Austin Vice chairmanVice chairman Feb.Feb. 10, 192410, 1924 – Jan. – Jan. 28, 201728, 2017 CharlesCharles LaMaistre, LaMaistre, M.D., M.D., was the was second the second full-time full-time president president of of JefferyJeffery D. Hildebrand, D. Hildebrand, Houston Houston Vice chairman Vice chairman The UniversityThe University of Texas of Texas MD AndersonMD Anderson Cancer Cancer Center, Center, serving serving ErnestErnest Aliseda, Aliseda, McAllen McAllen for 18for years, 18 years, from from 1978-1996. 1978-1996. Before Before taking taking the reins the reins from from DavidDavid J. Beck, J. Beck, Houston Houston R. LeeR. Clark, Lee Clark, M.D., M.D., LeMaistre LeMaistre spent spent seven seven years years as chancellor as chancellor of of The UniversityThe University of Texas of Texas System.
    [Show full text]
  • Regulation of Canonical and Non-Canonical NF Kappa B Signalling
    Regulation of Canonical and Non-Canonical NF kappa B Signalling in Lymphocytes by the Bcl10-MALT1 Complex By Michael Tusche A thesis submitted in conformity with the requirements for the degree of Docter of Philosophy Graduate Department of Immunology University of Toronto © Copyright by Michael Tusche (2010) Abstract of Thesis Regulation of Canonical and Non-Canonical NF kappa B Signalling in Lymphocytes by the Bcl10-MALT1 Complex 2010 Thesis for Doctor of Philosophy Graduate Department of Immunology University of Toronto The NF-κB family of heterodimeric transcription factors is activated by many stimuli, and lead to the upregulation of countless genes. Not surprisingly, NF-κB plays a critical role in many aspects of cellular function. In T and B lymphocytes, antigen receptor stimulation leads to the activation of NF-κB through a signal transduction cascade involving the Bcl10-MALT1 complex. We hypothesized that this complex may be critical to signalling cascades other than those emanating from antigen receptors. B cell activation factor of the TNF family (BAFF) activates non-canonical NF-κB heterodimers that promote B cell survival. Here, we show that MALT1 is required for BAFF-induced phosphorylation of NF-κB2 (p100), p100 degradation and RelB nuclear translocation in B220+ B cells. TRAF3, a known negative regulator of BAFF-R mediated signaling, interacts with MALT1 in a manner which is negatively regulated by BAFF, and TRAF3 levels are enhanced in MALT1-/- B cells. MALT1-/- CD21highCD23low (MZ) B cells show a defect in BAFF-induced survival and MALT1-/- x BAFF-transgenic (Tg) mice have decreased MZ and B1 B cell levels compared to BAFF-Tg mice.
    [Show full text]
  • Hepatocyte-Specific Pten Deficiency Results in Steatohepatitis and Hepatocellular Carcinomas
    Hepatocyte-specific Pten deficiency results in steatohepatitis and hepatocellular carcinomas Yasuo Horie, … , Tak Wah Mak, Toru Nakano J Clin Invest. 2004;113(12):1774-1783. https://doi.org/10.1172/JCI20513. Article Oncology PTEN is a tumor suppressor gene mutated in many human cancers, and its expression is reduced or absent in almost half of hepatoma patients. We used the Cre-loxP system to generate a hepatocyte-specific null mutation of Pten in mice (AlbCrePtenflox/flox mice). AlbCrePtenflox/flox mice showed massive hepatomegaly and steatohepatitis with triglyceride accumulation, a phenotype similar to human nonalcoholic steatohepatitis. Adipocyte-specific genes were induced in mutant hepatocytes, implying adipogenic-like transformation of these cells. Genes involved in lipogenesis and β-oxidation were also induced, possibly as a result of elevated levels of the transactivating factors PPARγ and SREBP1c. Importantly, the loss of Pten function in the liver led to tumorigenesis, with 47% of AlbCrePtenflox/flox livers developing liver cell adenomas by 44 weeks of age. By 74–78 weeks of age, 100% of AlbCrePtenflox/flox livers showed adenomas and 66% had hepatocellular carcinomas. AlbCrePtenflox/flox mice also showed insulin hypersensitivity. In vitro, AlbCrePtenflox/flox hepatocytes were hyperproliferative and showed increased hyperoxidation with abnormal activation of protein kinase B and MAPK. Pten is thus an important regulator of lipogenesis, glucose metabolism, hepatocyte homeostasis, and tumorigenesis in the liver. Find the latest
    [Show full text]
  • Masthead (PDF)
    PRESIDENT OF THE ACADEMY Cellular and Developmental Biology Joan E. Strassmann Thomas E. Shenk Marcia K. McNutt Denis Duboule Nils C. Stenseth Thomas J. Silhavy Brigid L. M. Hogan INTERIM EDITOR-IN-CHIEF Satyajit Mayor Genetics Physics Natasha V. Raikhel Roeland Nusse Kathryn V. Anderson Curtis G. Callan Jr. Michael Rosbash Sue Biggins Anthony Leggett ASSOCIATE EDITORS Gertrud M. Schüpbach John Carlson Herbert Levine Richard Eisenberg Iva S. Greenwald Cellular and Molecular Philip C. Hanawalt Alan Fersht Physiology and Pharmacology Dolores R. Piperno Neuroscience Mary-Claire King Douglas E. Koshland Richard W. Aldrich Christine E. Seidman David E. Clapham Susan G. Amara Neil H. Shubin Nancy Y. Ip Jasper Rine Allan C. Spradling Francisco Bezanilla Solomon H. Snyder Yuh-Nung Jan Arthur Karlin B. L. Turner II Jeremy Nathans Gail Mandel Peter K. Vogt Charles F. Stevens Human Environmental Sciences Stephen T. Warren Joseph S. Takahashi Anthony J. Bebbington Mary C. Waters Gina Turrigiano Ruth S. DeFries Plant Biology David A. Weitz Susan Hanson David Baulcombe Chemistry Emilio F. Moran Philip N. Benfey SPECIAL FEATURE EDITORS Stephen J. Benkovic Robert J. Scholes Joseph R. Ecker Josef Michl Michael L. Klein B. L. Turner II June B. Nasrallah J. Fraser Stoddart Raphael D. Levine Krishna K. Niyogi Immunology and Inflammation Thomas E. Mallouk Julian I. Schroeder Robert L. Coffman EDITORIAL BOARD Tobin J. Marks Peter Cresswell Catherine J. Murphy Plant, Soil, and Microbial Animal, Nutritional, and Peter J. Rossky K. Christopher Garcia Tak Wah Mak Sciences Applied Microbial Sciences Julia Bailey-Serres Stephen M. Beverley Philippa Marrack Computer and Information Sciences Ruslan Medzhitov Vicki L.
    [Show full text]