DOCSLIB.ORG

(51) International Patent Classification: A61P 35/00 (2006.01) G01N 33/50

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
(51) International Patent Classification: A61P 35/00 (2006.01) G01N 33/50 ( (51) International Patent Classification: Published: A61P 35/00 (2006.01) G01N 33/50 (2006.01) — with international search report (Art. 21(3)) G16H 50/20 (2018.01) A61K 39/00 (2006.01) G16H 50/30 (2018.01) (21) International Application Number: PCT/US20 19/058578 (22) International Filing Date: 29 October 2019 (29. 10.2019) (25) Filing Language: English (26) Publication Language: English (30) Priority Data: 62/752,288 29 October 2018 (29. 10.2018) US 62/788,3 13 04 January 2019 (04.01.2019) US 62/855,332 31 May 2019 (3 1.05.2019) US (71) Applicant: GENOCEA BIOSCIENCES, INC. [US/US]; Cambridge Discovery Park, 100 Acorn Park Drive, 5th Floor, Cambridge, Massachusetts 02140 (US). (72) Inventors: FLECHTNER, Jessica Baker; 1 Briant Drive, Sudbury, Massachusetts 01776 (US). DOBSON, Jason R.; 44 Pole Plain Road, Sharon, Massachusetts 02067 (US). (74) Agent: DAUKSS, Dana M. et al.; Choate, Hall & Ste¬ wart LLP, Two International Place, Boston, Massachusetts 021 10 (US). (81) Designated States (unless otherwise indicated, for every kind of national protection available) : AE, AG, AL, AM, AO, AT, AU, AZ, BA, BB, BG, BH, BN, BR, BW, BY, BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DJ, DK, DM, DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, HN, HR, HU, ID, IL, IN, IR, IS, JO, JP, KE, KG, KH, KN, KP, KR, KW, KZ, LA, LC, LK, LR, LS, LU, LY, MA, MD, ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM, PA, PE, PG, PH, PL, PT, QA, RO, RS, RU, RW, SA, SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM, TN, TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW. (84) Designated States (unless otherwise indicated, for every kind of regional protection available) : ARIPO (BW, GH, GM, KE, LR, LS, MW, MZ, NA, RW, SD, SL, ST, SZ, TZ, UG, ZM, ZW), Eurasian (AM, AZ, BY, KG, KZ, RU, TJ, TM), European (AL, AT, BE, BG, CH, CY, CZ, DE, DK, EE, ES, FI, FR, GB, GR, HR, HU, IE, IS, IT, LT, LU, LV, MC, MK, MT, NL, NO, PL, PT, RO, RS, SE, SI, SK, SM, TR), OAPI (BF, BJ, CF, CG, Cl, CM, GA, GN, GQ, GW, KM, ML, MR, NE, SN, TD, TG). Declarations under Rule 4.17: — as to applicant's entitlement to apply for and be granted a patent (Rule 4.17(H)) (54) Title: TREATMENT METHODS (57) Abstract: Methods and compositions for identifying tumor antigens of human lymphocytes, and for identifying subjects for cancer therapy, are provided herein. TREATMENT METHODS CROSS REFERENCE TO RELATED APPLICATIONS [0001] This application claims the benefit of U.S. Provisional Application No. 62/752,288, filed October 29, 2018, U.S. Provisional Application No. 62/788,313, filed January 4, 2019, and U.S. Provisional Application No. 62/855,332, filed May 31, 2019, the contents of each of which are hereby incorporated by reference herein in their entirety. BACKGROUND [0002] Cancer is characterized by proliferation of abnormal cells. Many treatments include costly and painful surgeries and chemotherapies. Although there is a growing interest in cancer therapies that target cancerous cells using a patient’s own immune system, such therapies have had limited success. SUMMARY [0003] The present invention features, inter alia, methods of identifying and/or selecting a cancer subject for initiation, continuation, modification, and/or discontinuation of a cancer therapy. [0004] Accordingly, one aspect of the disclosure featues a method of identifying a subject as a candidate for cancer therapy, the method comprising a) obtaining, providing, or generating a library comprising bacterial cells or beads comprising a plurality of tumor antigens, wherein each bacterial cell or bead of the library comprises a different tumor antigen; b) contacting the bacterial cells or beads with antigen presenting cells (APCs) from the subject, wherein the APCs internalize the bacterial cells or beads; c) contacting the APCs with lymphocytes from the subject, under conditions suitable for activation of lymphocytes by a tumor antigen presented by one or more APCs; d) determining whether one or more lymphocytes are activated by, or not responsive to, one or more tumor antigens presented by one or more APCs, e.g., by assessing (e.g, detecting or measuring) a level (e.g, an increased or decreased level, relative to a control), of expression and/or secretion of one or more immune mediators; e) identifying one or more tumor antigens as a stimulatory antigen and/or an inhibitory antigen; and f) generating a ratio of the number of stimulatory antigens to inhibitory antigens that represents the subject response profile; and g) comparing the subject response profile to a target response profile to select the subject as a candidate subject for initiation, continuation, modification, discontinuation or non initiation of a cancer therapy. [0005] In some embodiments, the method further comprises generating the target response profile by a method comprising h) contacting the bacterial cells or beads with antigen presenting cells (APCs) from a target subject, wherein the APCs internalize the bacterial cells or beads; i) contacting the APCs with lymphocytes from the target subject, under conditions suitable for activation of lymphocytes by a tumor antigen presented by one or more APCs; j) determining whether one or more lymphocytes are activated by, or not responsive to, one or more tumor antigens presented by one or more APCs, e.g., by assessing (e.g, detecting or measuring) a level (e.g, an increased or decreased level, relative to a control), of expression and/or secretion of one or more immune mediators; k) identifying one or more tumor antigens as a stimulatory antigen and/or inhibitory antigen; and 1) generating a ratio of the number of stimulatory antigens to inhibitory antigens that represents the target response profile. [0006] In some embodiments the target response profile is from one or more target subjects who exhibit or previously exhibited at least one beneficial response to cancer. In some embodiments, the target response profile comprises a ratio of the number of stimulatory antigens to the number of inhibitory antigens that is at least 100:1, 50:1, 20:1, 10:1, 5:1, 2:1, 1.5:1, 1.4:1, 1.2:1, 1.1:1 0.9:1, 0.8:1, 0.7:1, 0.6:1, or 0.5:1. In some embodiments the beneficial response comprises a positive clinical response to a cancer therapy or combination of therapies. In some embodiments, the beneficial response comprises a spontaneous response to a cancer. In some embodiments, the beneficial response comprises clearance of a cancer, e.g., a level of one or more clinical measures associated with clearance of a cancer. In some embodiments, the beneficial response comprises a lack of a relapse, recurrence, and/or metastasis of a cancer, e.g., over a defined period of time (e.g, at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 weeks, or at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 months, or at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 years). In some embodiments, the beneficial response comprises a positive cancer prognosis. In some embodiments, the beneficial response comprises a lack of one or more toxic responses and/or side effects (e.g., one or more measurable toxic responses or side effects) to a cancer therapy or combination of therapies. [0007] In some embodiments, the target response profile is from one or more target subjects who exhibit or previously exhibited one or more deleterious and/or non-beneficial response to cancer. In some embodiments, the target response profile comprises a ratio of the number of stimulatory antigens to the number of inhibitory antigens that is less than 5:1, 2:1, 1.5:1, 1.4:1, 1.2:1, 1.1:1 0.9:1, 0.8:1, 0.7:1, 0.6:1, 0.5:1, 0.25:1, 0.125:1, 0.01:1, or 0.001:1. In some embodiments, the deleterious and/or non-beneficial response comprises a negative clinical response and/or a failure to respond, to a cancer therapy or combination of therapies. In some embodiments, the deleterious and/or non-beneficial response comprises a lack of clearance of a cancer, e.g., a level of one or more clinical measures associated with lack of clearance of a cancer. In some embodiments, the deleterious and/or non-beneficial response comprises at least one relapse, recurrence, and/or metastasis of a cancer. In some embodiments, the deleterious and/or non-beneficial response comprises a negative cancer prognosis. In some embodiments, the deleterious and/or non-beneficial response comprises one or more toxic responses and/or side effects (e.g, one or more measurable toxic responses and/or side effects) to a cancer therapy or combination of therapies. [0008] In some embodiments, the method further comprises selecting the candidate subject for initiation of a cancer therapy or combination of cancer therapies. In some embodiments, the method further comprises selecting the candidate subject for continuation of a cancer therapy or combination of cancer therapies. In some embodiments, the method further comprises selecting the subject as a candidate subject if the subject response profile comprises ratio of the number of stimulatory antigens to the number of inhibitory antigens that is at least 100: 1, 50: 1, 20: 1, 10:1, 5:1, 2:1, 1.5:1, 1.4:1, 1.2:1, 1.1:1 0.9:1, 0.8:1, 0.7:1, 0.6:1, or 0.5:1.
Load more

Recommended publications
  • Small Cell Carcinoma of the Ovary, Hypercalcemic Type (SCCOHT) Beyond SMARCA4 Mutations: a Comprehensive Genomic Analysis
    cells Article Small Cell Carcinoma of the Ovary, Hypercalcemic Type (SCCOHT) beyond SMARCA4 Mutations: A Comprehensive Genomic Analysis Aurélie Auguste 1,Félix Blanc-Durand 2 , Marc Deloger 3 , Audrey Le Formal 1, Rohan Bareja 4,5, David C. Wilkes 4 , Catherine Richon 6,Béatrice Brunn 2, Olivier Caron 6, Mojgan Devouassoux-Shisheboran 7,Sébastien Gouy 2, Philippe Morice 2, Enrica Bentivegna 2, Andrea Sboner 4,5,8, Olivier Elemento 4,8, Mark A. Rubin 9 , Patricia Pautier 2, Catherine Genestie 10, Joanna Cyrta 4,9,11 and Alexandra Leary 1,2,* 1 Medical Oncologist, Gynecology Unit, Lead Translational Research Team, INSERM U981, Gustave Roussy, 94805 Villejuif, France; [email protected] (A.A.); [email protected] (A.L.F.) 2 Gynecological Unit, Department of Medicine, Gustave Roussy, 94805 Villejuif, France; [email protected] (F.B.-D.); [email protected] (B.B.); [email protected] (S.G.); [email protected] (P.M.); [email protected] (E.B.); [email protected] (P.P.) 3 Bioinformatics Core Facility, Gustave Roussy Cancer Center, UMS CNRS 3655/INSERM 23 AMMICA, 94805 Villejuif, France; [email protected] 4 Caryl and Israel Englander Institute for Precision Medicine, Weill Cornell Medicine, New York, NY 10001, USA; [email protected] (R.B.); [email protected] (D.C.W.); [email protected] (A.S.); [email protected] (O.E.); [email protected] (J.C.) 5 Institute for Computational Biomedicine, Weill Cornell
    [Show full text]
  • Genome-Wide Analysis of DNA Methylation, Copy Number Variation, and Gene Expression in Monozygotic Twins Discordant for Primary Biliary Cirrhosis
    UC Davis UC Davis Previously Published Works Title Genome-wide analysis of DNA methylation, copy number variation, and gene expression in monozygotic twins discordant for primary biliary cirrhosis. Permalink https://escholarship.org/uc/item/34d4m5nk Journal Frontiers in immunology, 5(MAR) ISSN 1664-3224 Authors Selmi, Carlo Cavaciocchi, Francesca Lleo, Ana et al. Publication Date 2014 DOI 10.3389/fimmu.2014.00128 Peer reviewed eScholarship.org Powered by the California Digital Library University of California ORIGINAL RESEARCH ARTICLE published: 28 March 2014 doi: 10.3389/fimmu.2014.00128 Genome-wide analysis of DNA methylation, copy number variation, and gene expression in monozygotic twins discordant for primary biliary cirrhosis Carlo Selmi 1,2*, Francesca Cavaciocchi 1,3, Ana Lleo4, Cristina Cheroni 5, Raffaele De Francesco5, Simone A. Lombardi 1, Maria De Santis 1,3, Francesca Meda1, Maria Gabriella Raimondo1, Chiara Crotti 1, Marco Folci 1, Luca Zammataro1, Marlyn J. Mayo6, Nancy Bach7, Shinji Shimoda8, Stuart C. Gordon9, Monica Miozzo10,11, Pietro Invernizzi 4, Mauro Podda1, Rossana Scavelli 5, Michelle R. Martin12, Michael F. Seldin13,14, Janine M. LaSalle 12 and M. Eric Gershwin2 1 Division of Rheumatology and Clinical Immunology, Humanitas Clinical and Research Center, Milan, Italy 2 Division of Rheumatology, Allergy, and Clinical Immunology, University of California at Davis, Davis, CA, USA 3 BIOMETRA Department, University of Milan, Milan, Italy 4 Liver Unit and Center for Autoimmune Liver Diseases, Humanitas Clinical and Research Center, Milan, Italy 5 National Institute of Molecular Genetics (INGM), Milan, Italy 6 University of Texas Southwestern, Dallas, TX, USA 7 Mt. Sinai University, NewYork, NY, USA 8 Clinical Research Center, National Nagasaki Medical Center, Nagasaki, Japan 9 Henry Ford Hospital, Detroit, MI, USA 10 Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy 11 Division of Pathology, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Milan, Italy 12 Genome Center and M.I.N.D.
    [Show full text]
  • Genome-Wide Analysis of Cancer/Testis Gene Expression
    Genome-wide analysis of cancer/testis gene expression Oliver Hofmanna,b,1, Otavia L. Caballeroc, Brian J. Stevensond,e, Yao-Tseng Chenf, Tzeela Cohenc, Ramon Chuac, Christopher A. Maherb, Sumir Panjib, Ulf Schaeferb, Adele Krugerb, Minna Lehvaslaihob, Piero Carnincig,h, Yoshihide Hayashizakig,h, C. Victor Jongeneeld,e, Andrew J. G. Simpsonc, Lloyd J. Oldc,1, and Winston Hidea,b aDepartment of Biostatistics, Harvard School of Public Health, 655 Huntington Avenue, SPH2, 4th Floor, Boston, MA 02115; bSouth African National Bioinformatics Institute, University of the Western Cape, Private Bag X17, Bellville 7535, South Africa; cLudwig Institute for Cancer Research, New York Branch at Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021; dLudwig Institute for Cancer Research, Lausanne Branch, 1015 Lausanne, Switzerland; eSwiss Institute of Bioinformatics, 1015 Lausanne, Switzerland; fWeill Medical College of Cornell University, 1300 York Avenue, New York, NY 10021; gGenome Exploration Research Group (Genome Network Project Core Group), RIKEN Genomic Sciences Center (GSC), RIKEN Yokohama Institute, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa, 230-0045, Japan; and hGenome Science Laboratory, Discovery Research Institute, RIKEN Wako Institute, 2-1 Hirosawa, Wako, Saitama, 3510198, Japan Contributed by Lloyd J. Old, October 28, 2008 (sent for review June 6, 2008) Cancer/Testis (CT) genes, normally expressed in germ line cells but expression profile information frequently limited to the original also activated in a wide range of cancer types, often encode defining articles. In some cases, e.g., ACRBP, the original antigens that are immunogenic in cancer patients, and present CT-restricted expression in normal tissues could not be con- potential for use as biomarkers and targets for immunotherapy.
    [Show full text]
  • A Comprehensive Analysis of the MAGE Family As Prognostic and Diagnostic Markers for Hepatocellular Carcinoma
    A Comprehensive Analysis of the MAGE Family as Prognostic and Diagnostic Markers for Hepatocellular Carcinoma Rong Li Guangdong Provincial Key Laboratory of Liver Disease Research, Guangdong province engineering laboratory for transplantation medicine, Third Aliated Hospital of Sun Yat-sen University Jiao Gong Department of Laboratory Medicine, Third Aliated Hospital of Sun Yat-sen University Cuicui Xiao Department of Anesthesiology, Cell-Gene therapy Translational Medicine Research Center, Third Aliated Hospital of Sun Yat-sen University Shuguang Zhu Department of Hepatic Surgery and Liver Transplantation Center, The Third Aliated Hospital of Sun Yat-sen University Zhongying Hu Guangdong provincial Key Laboratory of Liver Disease Research, Third Aliated Hospital of Sun Yat- sen University Jinliang Liang Guangdong Provincial Key Laboratory of Liver Disease Research, Third Aliated Hospital of Sun Yat- sen University Xuejiao Li Guangdong Provincial Key Laboratory of Liver Disease Research, Third Aliated Hospital of Sun Yat- sen University Xijing Yan Department of Hepatic Surgery and Liver Transplantation Center, Third Aliated Hospital of Sun Yat-sen University Xijian Zhang Department of Hepatic Surgery and Liver Transplantation Center, Third Aliated Hospital of Sun Yat-sen University Danyang Li Department of Infectious Diseases, Third Aliated Hospital of Sun Yat-sen University Wei Liu Guangdong Provincial Key Laboratory of Liver Disease Research, Guangdong province engineering laboratory for transplantation medicine, Third Aliated Hospital
    [Show full text]
  • View a Copy of This Licence, Visit
    Colemon et al. Genes and Environment (2020) 42:24 https://doi.org/10.1186/s41021-020-00162-2 RESEARCH Open Access DNA hypomethylation drives changes in MAGE-A gene expression resulting in alteration of proliferative status of cells Ashley Colemon1, Taylor M. Harris2 and Saumya Ramanathan2,3* Abstract Melanoma Antigen Genes (MAGEs) are a family of genes that have piqued the interest of scientists for their unique expression pattern. A subset of MAGEs (Type I) are expressed in spermatogonial cells and in no other somatic tissue, and then re-expressed in many cancers. Type I MAGEs are often referred to as cancer-testis antigens due to this expression pattern, while Type II MAGEs are more ubiquitous in expression. This study determines the cause and consequence of the aberrant expression of the MAGE-A subfamily of cancer-testis antigens. We have discovered that MAGE-A genes are regulated by DNA methylation, as revealed by treatment with 5-azacytidine, an inhibitor of DNA methyltransferases. Furthermore, bioinformatics analysis of existing methylome sequencing data also corroborates our findings. The consequence of expressing certain MAGE-A genes is an increase in cell proliferation and colony formation and resistance to chemo-therapeutic agent 5-fluorouracil and DNA damaging agent sodium arsenite. Taken together, these data indicate that DNA methylation plays a crucial role in regulating the expression of MAGE-A genes which then act as drivers of cell proliferation, anchorage-independent growth and chemo-resistance that is critical for cancer-cell survival. Keywords: Cancer, Cancer-testis antigens, Melanoma antigen genes, Anchorage-independent growth, Epigenetics, DNA methylation, Gene expression, Cell proliferation, Chemo-resistance Introduction antigens, and located on the X-chromosome, whereas Type Melanoma Antigen Genes (MAGEs) were first discovered II MAGEs are ubiquitous in expression and some members because a patient with melanoma and a few melanoma cell such as MAGEL2 are located on autosomes [3].
    [Show full text]
  • Cdna Microarray Analysis and Influx Transporter OATP1B1 in Liver Cells After Exposure to Gadoxetate Disodium, a Gadolinium-Based
    in vivo 32 : 677-684 (2018) doi:10.21873/invivo.11293 cDNA Microarray Analysis and Influx Transporter OATP1B1 in Liver Cells After Exposure to Gadoxetate Disodium, a Gadolinium-based Contrast Agent in MRI Liver Imaging CHI-CHENG LU 1* , WEN-KANG CHEN 2* , JO-HUA CHIANG 3, YUH-FENG TSAI 4, YU-NING JUAN 5, PING-CHIN LIN 6, YEU-SHENG TYAN 7,8,9 and JAI-SING YANG 5 1Department of Pharmacy, Buddhist Tzu Chi General Hospital, Hualien, Taiwan, R.O.C.; 2Department of Applied Cosmetology, National Tainan Junior College of Nursing, Tainan, Taiwan, R.O.C.; 3Department of Nursing, Chung Jen Catholic Junior College, Chiayi, Taiwan, R.O.C.; 4Department of Diagnostic Radiology, Shin-Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan, R.O.C.; 5Department of Medical Research, China Medical University Hospital, China Medical University, Taichung, Taiwan, R.O.C.; 6Department of Medical Imaging, Chia-Yi Christian Hospital, Chiayi, Taiwan, R.O.C.; 7Department of Medical Imaging, Chung Shan Medical University Hospital, Taichung, Taiwan, R.O.C.; 8School of Medical Imaging and Radiological Sciences, 9School of Medicine, Chung Shan Medical University, Taichung, Taiwan, R.O.C. Abstract. Background/Aim: Gadoxetate disodium (Primovist western blotting. Results: Gadoxetate disodium at 5 and 10 or Eovist) is extensively used as a hepatospecific contrast agent mM failed to induce any cell cytotoxicity and morphological during magnetic resonance imaging (MRI) examinations. changes in Chang Liver cells. Our data demonstrated that However, there is no information determining whether gadoxetate disodium significantly enhanced the expression of gadoxetate disodium has a cytotoxic impact and/or affects 29 genes and suppressed that of 27.
    [Show full text]
  • High Resolution X Chromosome-Specific Array-CGH Detects New Cnvs in Infertile Males
    High Resolution X Chromosome-Specific Array-CGH Detects New CNVs in Infertile Males Csilla Krausz1,2*, Claudia Giachini1, Deborah Lo Giacco2,3, Fabrice Daguin1, Chiara Chianese1, Elisabet Ars3, Eduard Ruiz-Castane2, Gianni Forti4, Elena Rossi5 1 Unit of Sexual Medicine and Andrology, Molecular Genetic Laboratory, Department of Clinical Physiopathology, University of Florence, Florence, Italy, 2 Andrology Service, Fundacio´ Puigvert, Barcelona, Spain, 3 Molecular Biology Laboratory, Fundacio´ Puigvert, Universitat Auto`noma de Barcelona, Barcelona, Spain, 4 Endocrinology Unit, Department of Clinical Physiopathology, University of Florence, Florence, Italy, 5 Biology and Medical Genetics, University of Pavia, Pavia, Italy Abstract Context: The role of CNVs in male infertility is poorly defined, and only those linked to the Y chromosome have been the object of extensive research. Although it has been predicted that the X chromosome is also enriched in spermatogenesis genes, no clinically relevant gene mutations have been identified so far. Objectives: In order to advance our understanding of the role of X-linked genetic factors in male infertility, we applied high resolution X chromosome specific array-CGH in 199 men with different sperm count followed by the analysis of selected, patient-specific deletions in large groups of cases and normozoospermic controls. Results: We identified 73 CNVs, among which 55 are novel, providing the largest collection of X-linked CNVs in relation to spermatogenesis. We found 12 patient-specific deletions with potential clinical implication. Cancer Testis Antigen gene family members were the most frequently affected genes, and represent new genetic targets in relationship with altered spermatogenesis. One of the most relevant findings of our study is the significantly higher global burden of deletions in patients compared to controls due to an excessive rate of deletions/person (0.57 versus 0.21, respectively; p = 8.78561026) and to a higher mean sequence loss/person (11.79 Kb and 8.13 Kb, respectively; p = 3.43561024).
    [Show full text]
  • Extratumoral Effects of Highly Aggressive Prostate Cancer
    Extratumoral Effects of Highly Aggressive Prostate Cancer Kerstin Strömvall Department of Medical Biosciences Umeå 2017 Responsible publisher under swedish law: the Dean of the Medical Faculty This work is protected by the Swedish Copyright Legislation (Act 1960:729) ISBN: 978-91-7601-770-8 ISSN: 0346-6612, New series No.: 1918 Electronic version is available at http://umu.diva-portal.org/ Printed by: Umu Printing Service, Umeå University Umeå, Sweden 2017 “The more you know, the more you know you don't know.” ― Aristotle Table of Contents Table of Contents i Abstract iii Populärvetenskaplig sammanfattning iv Abbreviations vii Gene/Protein symbols and names viii List of Papers xi Paper I xi Paper II xi Paper III xi Introduction 1 Prostate Cancer 1 The Hallmarks of Cancer 2 Tumor Immunity 3 Lymph Node Anatomy and Function 6 Tumor-Induced Systemic Effects 9 The Lymph Node Pre-Metastatic Niche 10 TINT 12 Aims of the Thesis 13 Overall aim 13 Specific aims 13 Materials and Methods 15 Patient Cohort 15 Dunning Model 15 Experimental Design 16 Whole Genome Gene Expression Microarray 18 qRT-PCR 19 IHC 21 Results and Discussion 23 The Pro-Metastatic Tumor Micro-and Macroenvironment 23 Tumor Immunity and Establishment of a Lymph Node Pre-Metastatic Niche 25 Clinical Relevance 28 General Discussion 30 Conclusions 35 Acknowledgements 36 References 40 i ii Abstract Prostate cancer (PC) is the most common cancer in Sweden. Most patients have slow growing tumors that will not cause them any harm within their lifetime, but some have aggressive tumors and will die from their disease.
    [Show full text]
  • MAGEA9 (Human) Matched Antibody Pair
    MAGEA9 (Human) Matched Antibody Pair Catalog # : H00004108-AP51 規格 : [ 1 Set ] List All Specification Application Image Product This antibody pair set comes with matched antibody pair to detect and ELISA Pair (Transfected lysate) Description: quantify protein level of human MAGEA9. Reactivity: Human Quality Control Standard curve using MAGEA9 293T overexpression lysate (non- Testing: denatured) as an analyte. Sandwich ELISA detection sensitivity ranging from approximately 729x to 3x dilution of the MAGEA9 293T overexpression lysate (non-denatured). Supplied Antibody pair set content: Product: 1. Capture antibody: mouse monoclonal anti-MAGEA9 (100 ug) 2. Detection antibody: rabbit purified polyclonal anti-MAGEA9 (50 ug) *Reagents are sufficient for at least 3-5 x 96 well plates using recommended protocols. Storage Store reagents of the antibody pair set at -20°C or lower. Please aliquot Instruction: to avoid repeated freeze thaw cycle. Reagents should be returned to - 20°C storage immediately after use. MSDS: Download Datasheet: Download Applications ELISA Pair (Transfected lysate) Protocol Download Gene Information Entrez GeneID: 4108 Gene Name: MAGEA9 Gene Alias: MAGE9,MGC8421 Gene melanoma antigen family A, 9 Description: Omim ID: 300342 Page 1 of 2 2021/6/17 Gene Ontology: Hyperlink Gene Summary: This gene is a member of the MAGEA gene family. The members of this family encode proteins with 50 to 80% sequence identity to each other. The promoters and first exons of the MAGEA genes show considerable variability, suggesting that the existence of this gene family enables the same function to be expressed under different transcriptional controls. The MAGEA genes are clustered at chromosomal location Xq28.
    [Show full text]
  • Genetic Investigation in Non-Obstructive Azoospermia: from the X Chromosome to The
    DOTTORATO DI RICERCA IN SCIENZE BIOMEDICHE CICLO XXIX COORDINATORE Prof. Persio dello Sbarba Genetic investigation in non-obstructive azoospermia: from the X chromosome to the whole exome Settore Scientifico Disciplinare MED/13 Dottorando Tutore Dott. Antoni Riera-Escamilla Prof. Csilla Gabriella Krausz _______________________________ _____________________________ (firma) (firma) Coordinatore Prof. Carlo Maria Rotella _______________________________ (firma) Anni 2014/2016 A la meva família Agraïments El resultat d’aquesta tesis és fruit d’un esforç i treball continu però no hauria estat el mateix sense la col·laboració i l’ajuda de molta gent. Segurament em deixaré molta gent a qui donar les gràcies però aquest són els que em venen a la ment ara mateix. En primer lloc voldria agrair a la Dra. Csilla Krausz por haberme acogido con los brazos abiertos desde el primer día que llegué a Florencia, por enseñarme, por su incansable ayuda y por contagiarme de esta pasión por la investigación que nunca se le apaga. Voldria agrair també al Dr. Rafael Oliva per haver fet possible el REPROTRAIN, per haver-me ensenyat moltíssim durant l’època del màster i per acceptar revisar aquesta tesis. Alhora voldria agrair a la Dra. Willy Baarends, thank you for your priceless help and for reviewing this thesis. També voldria donar les gràcies a la Dra. Elisabet Ars per acollir-me al seu laboratori a Barcelona, per ajudar-me sempre que en tot el què li he demanat i fer-me tocar de peus a terra. Ringrazio a tutto il gruppo di Firenze, che dal primo giorno mi sono trovato come a casa.
    [Show full text]
  • Epigenetic Upregulation of MAGE-A Isoforms Promotes Breast Cancer Cell Aggressiveness
    cancers Article Epigenetic Upregulation of MAGE-A Isoforms Promotes Breast Cancer Cell Aggressiveness Chaeun Oh 1,† , Hwa-Ryeon Kim 2,†, Sumin Oh 1,3, Je Yeong Ko 4, Yesol Kim 4, Keunsoo Kang 5 , Young Yang 4 , Jongmin Kim 4 , Jong Hoon Park 4, Jae-Seok Roe 2,* and Kyung Hyun Yoo 1,3,* 1 Laboratory of Biomedical Genomics, Department of Biological Sciences, Sookmyung Women’s University, Seoul 04310, Korea; [email protected] (C.O.); [email protected] (S.O.) 2 Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul 03722, Korea; [email protected] 3 Research Institute of Women’s Health, Sookmyung Women’s University, Seoul 04310, Korea 4 Department of Biological Sciences, Sookmyung Women’s University, Seoul 04310, Korea; [email protected] (J.Y.K.); [email protected] (Y.K.); [email protected] (Y.Y.); [email protected] (J.K.); [email protected] (J.H.P.) 5 Department of Microbiology, College of Science & Technology, Dankook University, Cheonan 31116, Korea; [email protected] * Correspondence: [email protected] (J.-S.R.); [email protected] (K.H.Y.); Tel.: +82-2-2123-2700 (J.-S.R.); +82-2-2077-7836 (K.H.Y.) † These authors contributed equally to the work. Simple Summary: Breast cancer is a heterogeneous disease that has complex causes and mechanisms of development. Currently, patient treatment options depend on the breast cancer molecular subtype, which is classified based on the presence or absence of hormone receptors and HER2. However, this Citation: Oh, C.; Kim, H.-R.; Oh, S.; classification system has limitations in terms of predicting responsiveness to anticancer drugs and Ko, J.Y.; Kim, Y.; Kang, K.; Yang, Y.; patient outcomes.
    [Show full text]
  • Supplementary Methods
    Supplementary Methods Patient Cohorts and Clinicopathological Review AOCS and Clinical Cohort AOCS is a population-based, case control study of ovarian cancer which recruited eligible women aged 18-79 years with newly diagnosed epithelial ovarian cancer (including primary peritoneal and fallopian tube cancer) through 20 gynaecologic oncology units across all Australian states, between January 2002 and June 2006. Women who were unable to provide informed consent due to illness, language difficulties or mental incapacity were excluded, as were those whose diagnosis was not histopathologically confirmed. Detailed clinical and follow-up data was obtained from medical records at predefined intervals: post surgery, post primary chemotherapy, at 6-monthly intervals to 5 years and annually thereafter. All treatment details and clinical assessments were recorded on case report forms using Good Clinical Practice (GCP) guidelines (ICH E6: Good Clinical Practice: Consolidated Guidance. 1996; http://www.fda.gov/oc/gcp/guidance.html), and included chemotherapy regimen, imaging details and pre- and post-treatment serum CA125 levels. The CA125 assay type and upper limit of normal for each measurement were recorded and assignment of relapse date was based on Gynecologic Cancer Intergroup (GCIG) criteria1. Clinical details for the cases from The Royal Brisbane Hospital, and Westmead Hospital were obtained retrospectively from medical records. The majority of patients with invasive ovarian cancer (n= 267) underwent laparotomy for diagnosis, staging and debulking and subsequently received first-line platinum/taxane based chemotherapy. In most cases, tumor examined was excised at the time of primary surgery, prior to the administration of chemotherapy. Eighteen patients who had neoadjuvant, platinum based chemotherapy were also included in the study as were 18 patients with low malignant potential disease.
    [Show full text]