DOCSLIB.ORG

Detection of Prostate Cancer and Predicting Progression: Current and Future Diagnostic Markers

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Detection of Prostate Cancer and Predicting Progression: Current and Future Diagnostic Markers Vol. 10, 3943–3953, June 15, 2004 Clinical Cancer Research 3943 Review Detection of Prostate Cancer and Predicting Progression: Current and Future Diagnostic Markers James V. Tricoli,1 Mason Schoenfeldt,3 and of serum prostate-specific antigen (PSA) screening of asymp- Barbara A. Conley2 tomatic populations, prostate cancer incidence rates have in- creased dramatically, as has the number of men undergoing 1Diagnostics Research Branch, Cancer Diagnosis Program, National Cancer Institute, Rockville, Maryland; 2Aerodigestive Clinical Cancer radical prostatectomy and radiation therapy for this disease (1, Research Section, Center for Cancer Research, National Cancer 2). However, false positives for PSA continue to be a significant Institute, Bethesda, Maryland; and 3The EMMES Corporation, problem resulting in unnecessary biopsies, and the value of Rockville, Maryland broad-based PSA testing with regard to predicting surgical cures has recently come into question (3). ABSTRACT Currently, there are no markers that differentiate clinically Carcinoma of the prostate is the second leading cause of relevant from clinically benign disease. Better indicators of male cancer-related death in the United States. Better indi- prostate cancer presence and progression are needed to avoid cators of prostate cancer presence and progression are unnecessary treatment, predict disease course, and develop more needed to avoid unnecessary treatment, predict disease effective therapy. A variety of putative prostate cancer markers course, and develop more effective therapy. Numerous mo- have been described in human serum, urine, seminal fluid, and lecular markers have been described in human serum, histological specimens. These markers exhibit varying capaci- urine, seminal fluid, and histological specimens that exhibit ties to detect prostate cancer and to predict disease course. These varying capacities to detect prostate cancer and predict markers are distinct from chromosomal aberrations that have disease course. However, to date, few of these markers have been associated with prostate cancer, which will not be dealt been adequately validated for clinical use. The purpose of with here (4). this review is to examine the current status of these markers The purpose of this review is to examine the current status in prostate cancer and to assess the diagnostic potential for of markers in prostate cancer and to assess the diagnostic future markers from identified genes and molecules that potential for future markers from identified genes and molecules display loss, mutation, or alteration in expression between that display loss, mutation, or alteration in expression between tumor and normal prostate tissues. In this review we cite 91 tumor and normal prostate tissues. To date, few of these markers molecular markers that display some level of correlation have achieved widespread clinical utility. If we are to improve with prostate cancer presence, disease progression, can- on the treatment of prostate cancer in the 21st century, we must cer recurrence, prediction of response to therapy, and/or identify and develop markers that are more clinically informa- disease-free survival. We suggest criteria to consider when tive for this disease and that will allow risk-based individual- selecting a marker for further development as a clinical tool ization of therapy. and discuss five examples of markers (chromogranin A, glutathione S-transferase ␲ 1, prostate stem cell antigen, A BRIEF HISTORY OF PROSTATE prostate-specific membrane antigen, and telomerase reverse transcriptase) that fulfill some of these criteria. Finally, we CANCER DIAGNOSTICS discuss how to conduct evaluations of candidate prostate The first documented case of prostate cancer was reported cancer markers and some of the issues involved in the by Langstaff in 1817 (5). One hundred eighteen years later, in validation process. 1935, prostatic acid phosphatase (PAP) levels were identified in the ejaculate of men, thus linking this enzyme to the prostate (6). Subsequent studies showed high PAP concentrations in primary INTRODUCTION and metastatic prostate cancer tissues and in human serum, Carcinoma of the prostate is the second leading cause of making it the first candidate marker for the diagnosis of prostate male cancer-related death in the United States, and it is esti- cancer (7, 8). Reductions in serum PAP levels were found to mated that in 2003 there were approximately 220,900 new cases occur in response to antiandrogen therapy, whereas increasing and 28,900 deaths from this disease (1). Since the introduction serum levels were associated with treatment failure and relapse (9, 10). However, whereas serum PAP levels were elevated in a significant number of men with metastatic disease (8), fewer than 20% of men with localized prostate cancer exhibited ab- Received 9/10/03; revised 3/16/04; accepted 3/26/04. normal enzyme levels (11, 12). Meticulous sample collection The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked and preparation were required because both platelets and leu- advertisement in accordance with 18 U.S.C. Section 1734 solely to kocytes are contaminating sources of acid phosphatases (13) and indicate this fact. because PAP activity is rapidly lost at room temperature (14). Requests for reprints: James V. Tricoli, Diagnostics Research Branch, Development of a radioimmune assay for PAP in 1975 provided Cancer Diagnosis Program, National Cancer Institute, 6130 Executive Boulevard, Executive Plaza North, Suite 6044, Rockville, MD 20852. some improvement in test sensitivity (15), but the sensitivity Phone: (301) 496-1591; Fax: (301) 402-7819; E-mail: tricolij@mail. levels were still inadequate for detection of early-stage disease. nci.nih.gov. Therefore, it was clear that a more sensitive and robust indicator Downloaded from clincancerres.aacrjournals.org on October 1, 2021. © 2004 American Association for Cancer Research. 3944 Prostate Cancer Diagnostics of disease presence would be required to detect prostate cancer correlation with one or more of the following factors: presence in its earlier stages, when cure is more likely. of prostate cancer, disease progression, cancer recurrence, pre- PSA is a kallekrein-like serine protease that was first diction of response to therapy, or disease-free survival. Infor- described in 1971 (16). PSA is secreted from prostate epithelial mation on these markers was accumulated through literature cells and encoded by an androgen-responsive gene located on searches using PubMed and from the GeneCards database of chromosome 19q13.3–13.4 (17). The main function of PSA is to human genes, their products, and their involvement in diseases liquefy human semen through its proteolytic action (18). PSA (31). Evidence for the association of a specific marker with was initially thought to be a prostate-specific protein; however, human prostate cancer range from a single publication, as in the subsequent investigations demonstrated that PSA is secreted in case of UROC 28, to thousands of publications, as in the case of small quantities from a number of other normal male tissues and PSA. In light of the rapid pace of new marker discovery through even some female tissues (19, 20). PSA was first detected in the the use of comprehensive DNA expression analysis and pro- serum of prostate cancer patients in 1980 (19), and a normal teomics, there are no doubt candidate markers missing from this PSA serum concentration limit of 4 ng/ml for men was subse- list. However, we have made Table 1 as current as possible, and quently established (20). A serum level above 4 ng/ml was taken we hope that it will serve as a resource for the prostate cancer as an indicator of the possible presence of prostate cancer and research community. In Table 1, we present 89 proteins (the served as the trigger for further clinical evaluation. Eventually, transcripts for DD3 and PCGEM1 do not contain open reading a number of studies enrolling large numbers of men over the age frames) that have been correlated with some aspect of prostate of 50 years suggested that quantitation of serum PSA was a cancer presence or progression in one or more studies. They are useful diagnostic tool for detecting the presence of prostate listed in alphabetical order and categorized according to their cancer, particularly when combined with digital rectal exami- subcellular location: nucleus; cytoplasm; plasma membrane; nation (21–24). However, other studies have called into question cytoskeleton; mitochondria; microsomal membrane; endoplas- the sensitivity and specificity of the PSA test (25–28). One mic reticulum; lysosome; or secreted. The latest information on problem is that serum PSA levels can be elevated as a result of chromosomal location and molecular weight is included, along conditions other than prostate cancer, such as benign prostatic with the most common biochemical function of the protein and hypertrophy (BPH) and prostatitis. As a result, false positives its major cellular function. In cases in which the biochemical are a significant problem for the PSA test and can lead to and/or cellular functions of the proteins remain to be deter- unnecessary biopsies and other interventions. Of greater con- mined, the word “unknown” appears in the appropriate column. cern, 20–30% of men with prostate cancer have serum PSA Alterations for some of these markers, such as p53 and telom- levels in the normal range, resulting
Load more

Recommended publications
  • Gene Symbol Gene Description ACVR1B Activin a Receptor, Type IB
    Table S1. Kinase clones included in human kinase cDNA library for yeast two-hybrid screening Gene Symbol Gene Description ACVR1B activin A receptor, type IB ADCK2 aarF domain containing kinase 2 ADCK4 aarF domain containing kinase 4 AGK multiple substrate lipid kinase;MULK AK1 adenylate kinase 1 AK3 adenylate kinase 3 like 1 AK3L1 adenylate kinase 3 ALDH18A1 aldehyde dehydrogenase 18 family, member A1;ALDH18A1 ALK anaplastic lymphoma kinase (Ki-1) ALPK1 alpha-kinase 1 ALPK2 alpha-kinase 2 AMHR2 anti-Mullerian hormone receptor, type II ARAF v-raf murine sarcoma 3611 viral oncogene homolog 1 ARSG arylsulfatase G;ARSG AURKB aurora kinase B AURKC aurora kinase C BCKDK branched chain alpha-ketoacid dehydrogenase kinase BMPR1A bone morphogenetic protein receptor, type IA BMPR2 bone morphogenetic protein receptor, type II (serine/threonine kinase) BRAF v-raf murine sarcoma viral oncogene homolog B1 BRD3 bromodomain containing 3 BRD4 bromodomain containing 4 BTK Bruton agammaglobulinemia tyrosine kinase BUB1 BUB1 budding uninhibited by benzimidazoles 1 homolog (yeast) BUB1B BUB1 budding uninhibited by benzimidazoles 1 homolog beta (yeast) C9orf98 chromosome 9 open reading frame 98;C9orf98 CABC1 chaperone, ABC1 activity of bc1 complex like (S. pombe) CALM1 calmodulin 1 (phosphorylase kinase, delta) CALM2 calmodulin 2 (phosphorylase kinase, delta) CALM3 calmodulin 3 (phosphorylase kinase, delta) CAMK1 calcium/calmodulin-dependent protein kinase I CAMK2A calcium/calmodulin-dependent protein kinase (CaM kinase) II alpha CAMK2B calcium/calmodulin-dependent
    [Show full text]
  • BIOINFORMATICS DOI: 10.1093/Bioinformatics/Btg1030
    Vol. 19 Suppl. 1 2003, pages i222–i224 BIOINFORMATICS DOI: 10.1093/bioinformatics/btg1030 GeneLoc: exon-based integration of human genome maps Naomi Rosen, Vered Chalifa-Caspi, Orit Shmueli, Avital Adato, Michal Lapidot, Julie Stampnitzky, Marilyn Safran ∗ and Doron Lancet Weizmann Institute of Science, Rehovot, Israel Received on January 6, 2003; accepted on February 20, 2003 ABSTRACT to provide a comprehensive gene list, NCBI’s LocusLink Motivation: Despite the numerous available whole- contains thousands of model genes, categorized by level genome mapping resources, no comprehensive, inte- and type of support. Even known genes appearing in every grated map of the human genome yet exists. database may have different names in each database. The Results: GeneLoc, software adjunct to GeneCards and biologist must move among databases to figure out which UDB, integrates gene lists by comparing genomic coordi- genes are the same, and which could be a novel gene nates at the exon level and assigns unique and meaningful sought. UCSC’s Genome Browser website maps genes identifiers to each gene. from several sources on the same scale, but the maps are Availability: http://bioinfo.weizmann.ac.il/genecards and not integrated, making it difficult to relate genes from http://genecards.weizmann.ac.il/udb different sources. As stated (Jongeneel, 2000),‘there is an Supplementary information: http://bioinfo.weizmann.ac. urgent need for a human gene index that can be used to il/cards-bin/AboutGCids.cgi, http://genecards.weizmann. identify transcripts unambiguously.’ The author contends ac.il/GeneLocAlg.html that this index should have, among others, the following Contact: [email protected] qualities: comprehensiveness, uniqueness, and stability.
    [Show full text]
  • Long Noncoding RNA and Cancer: a New Paradigm Arunoday Bhan, Milad Soleimani, and Subhrangsu S
    Published OnlineFirst July 12, 2017; DOI: 10.1158/0008-5472.CAN-16-2634 Cancer Review Research Long Noncoding RNA and Cancer: A New Paradigm Arunoday Bhan, Milad Soleimani, and Subhrangsu S. Mandal Abstract In addition to mutations or aberrant expression in the moting (oncogenic) functions. Because of their genome-wide protein-coding genes, mutations and misregulation of noncod- expression patterns in a variety of tissues and their tissue- ing RNAs, in particular long noncoding RNAs (lncRNA), appear specific expression characteristics, lncRNAs hold strong prom- to play major roles in cancer. Genome-wide association studies ise as novel biomarkers and therapeutic targets for cancer. In of tumor samples have identified a large number of lncRNAs this article, we have reviewed the emerging functions and associated with various types of cancer. Alterations in lncRNA association of lncRNAs in different types of cancer and dis- expression and their mutations promote tumorigenesis and cussed their potential implications in cancer diagnosis and metastasis. LncRNAs may exhibit tumor-suppressive and -pro- therapy. Cancer Res; 77(15); 1–17. Ó2017 AACR. Introduction lncRNAs (lincRNA) originate from the region between two pro- tein-coding genes; enhancer lncRNAs (elncRNA) originate from Cancer is a complex disease associated with a variety of genetic the promoter enhancer regions; bidirectional lncRNAs are local- mutations, epigenetic alterations, chromosomal translocations, ized within the vicinity of a coding transcript of the opposite deletions, and amplification (1). Noncoding RNAs (ncRNA) are strand; sense-overlapping lncRNAs overlap with one or more an emerging class of transcripts that are coded by the genome but introns and exons of different protein-coding genes in the sense are mostly not translated into proteins (2).
    [Show full text]
  • Association of MUC1 5640G>A and PSCA 5057C>T Polymorphisms
    Alikhani et al. BMC Medical Genetics (2020) 21:148 https://doi.org/10.1186/s12881-020-01085-z RESEARCH ARTICLE Open Access Association of MUC1 5640G>A and PSCA 5057C>T polymorphisms with the risk of gastric cancer in Northern Iran Reza Alikhani1, Ali Taravati1 and Mohammad Bagher Hashemi-Soteh2* Abstract Background: Gastric cancer is one of the four most common cancer that causing death worldwide. Genome-Wide Association Studies (GWAS) have shown that genetic diversities MUC1 (Mucin 1) and PSCA (Prostate Stem Cell Antigen) genes are involved in gastric cancer. The aim of this study was avaluating the association of rs4072037G > A polymorphism in MUC1 and rs2294008 C > T in PSCA gene with risk of gastric cancer in northern Iran. Methods: DNA was extracted from 99 formalin fixed paraffin-embedded (FFPE) tissue samples of gastric cancer and 96 peripheral blood samples from healthy individuals (sex matched) as controls. Two desired polymorphisms, 5640G > A and 5057C > T for MUC1 and PSCA genes were genotyped using PCR-RFLP method. Results: The G allele at rs4072037 of MUC1 gene was associated with a significant decreased gastric cancer risk (OR = 0.507, 95% CI: 0.322–0.799, p = 0.003). A significant decreased risk of gastric cancer was observed in people with either AG vs. AA, AG + AA vs. GG and AA+GG vs. AG genotypes of MUC1 polymorphism (OR = 4.296, 95% CI: 1.190–15.517, p =0.026), (OR = 3.726, 95% CI: 2.033–6.830, p = 0.0001) and (OR = 0.223, 95% CI: 0.120–0.413, p = 0.0001) respectively.
    [Show full text]
  • Genome Analysis and Knowledge
    Dahary et al. BMC Medical Genomics (2019) 12:200 https://doi.org/10.1186/s12920-019-0647-8 SOFTWARE Open Access Genome analysis and knowledge-driven variant interpretation with TGex Dvir Dahary1*, Yaron Golan1, Yaron Mazor1, Ofer Zelig1, Ruth Barshir2, Michal Twik2, Tsippi Iny Stein2, Guy Rosner3,4, Revital Kariv3,4, Fei Chen5, Qiang Zhang5, Yiping Shen5,6,7, Marilyn Safran2, Doron Lancet2* and Simon Fishilevich2* Abstract Background: The clinical genetics revolution ushers in great opportunities, accompanied by significant challenges. The fundamental mission in clinical genetics is to analyze genomes, and to identify the most relevant genetic variations underlying a patient’s phenotypes and symptoms. The adoption of Whole Genome Sequencing requires novel capacities for interpretation of non-coding variants. Results: We present TGex, the Translational Genomics expert, a novel genome variation analysis and interpretation platform, with remarkable exome analysis capacities and a pioneering approach of non-coding variants interpretation. TGex’s main strength is combining state-of-the-art variant filtering with knowledge-driven analysis made possible by VarElect, our highly effective gene-phenotype interpretation tool. VarElect leverages the widely used GeneCards knowledgebase, which integrates information from > 150 automatically-mined data sources. Access to such a comprehensive data compendium also facilitates TGex’s broad variant annotation, supporting evidence exploration, and decision making. TGex has an interactive, user-friendly, and easy adaptive interface, ACMG compliance, and an automated reporting system. Beyond comprehensive whole exome sequence capabilities, TGex encompasses innovative non-coding variants interpretation, towards the goal of maximal exploitation of whole genome sequence analyses in the clinical genetics practice. This is enabled by GeneCards’ recently developed GeneHancer, a novel integrative and fully annotated database of human enhancers and promoters.
    [Show full text]
  • Full Review Molecular Disease Presentation in Diabetic Nephropathy
    Nephrol Dial Transplant (2015) 30: iv17–iv25 doi: 10.1093/ndt/gfv267 Full Review Molecular disease presentation in diabetic nephropathy Downloaded from https://academic.oup.com/ndt/article/30/suppl_4/iv17/2324968 by guest on 25 September 2021 Andreas Heinzel1, Irmgard Mühlberger1, Gil Stelzer2, Doron Lancet2, Rainer Oberbauer3, Maria Martin4 and Paul Perco1 1emergentec biodevelopment GmbH, Vienna, Austria, 2Weizmann Institute of Science, Rehovot, Israel, 3Medical University of Vienna, Vienna, Austria and 4EMBL-EBI, Wellcome Trust Genome Campus, Hinxton, UK Correspondence and offprint requests to: Paul Perco; E-mail: [email protected] ABSTRACT INTRODUCTION Diabetic nephropathy, as the most prevalent chronic disease of Kidney disease is a common problem in patients with diabetes. the kidney, has also become the primary cause of end-stage Depending on the degree of GFR impairment and/or albumin- renal disease with the incidence of kidney disease in type 2 dia- uria, roughly 30% of subjects are affected. As with most betics continuously rising. As with most chronic diseases, the diabetes-associated comorbidities, the pathophysiology is pathophysiology is multifactorial with a number of deregulated multifactorial and the molecular pathways involved in the ini- molecular processes contributing to disease manifestation and tiation and progression constitute a wide and complex as well as progression. Current therapy mainly involves interfering in the redundant network of regulators. Considerable success has renin–angiotensin–aldosterone
    [Show full text]
  • (12) United States Patent (10) Patent No.: US 7,807,373 B2 Srivastava Et Al
    US007807373B2 (12) United States Patent (10) Patent No.: US 7,807,373 B2 Srivastava et al. (45) Date of Patent: Oct. 5, 2010 (54) PROSTATE SPECIFIC GENE, PCGEM1, AND GenBank. Accession No. ACO 13401, GI:8569780, 169700 bp DNA, METHODS OF USING PCEGM1 TO DETECT, Jul. 7, 2000. TREAT, AND PREVENT PROSTATE CANCER “AC003046.” EBI Database XPO02143197, Dec. 1, 2001. (75) Inventors: Shiv Srivastava, Potomac, MD (US); Srikantanet al., “Structure and Expression of a Novel Prostate Spe Judd W. Moul, Bethesda, MD (US); cific Gene: PCGEM1. Proc. American Assoc. Cancer Research Vasantha Srikantan, Rockville, MD Annual, XP000929230, vol. 40, p. 37 (Mar. 1999). (US); Zhiqiang Zou, Gaithersburg, MD Bussemakers et al., “A New Prostate-Specific Arker, Strongly (US) Overexpressed in Prostatic Tumors.” Urological Research, XP0020743.05, vol. 25, No. 1, p. 76 (Feb. 1997). (73) Assignee: Henry M. Jackson Foundation for the Wang et al., “Genes Regulated by Androgen in the Rat Ventral Pros Advancement of Military Medicine, tate.” Proc. Nat.1 Acad. Sci., U.S.A., vol. 94, pp. 12999-13004 (Nov. Rockville, MD (US) 1997). “ACO 13401, EBI Database XP002143200, Apr. 16, 2005. (*) Notice: Subject to any disclaimer, the term of this Srikantan et al., “PCGEM1, a Prostate-Specific Gene, Is Overex patent is extended or adjusted under 35 posed in Prostate Cancer.” Proc. Natl. Acad. Sci., vol.97, No. 22, pp. U.S.C. 154(b) by 285 days. 12216-12221 (Oct. 24, 2000). (21) Appl. No.: 12/166,723 Srikantan et al., Identification of Prostate Cancer Associated Novel Gene Expression Alterations, Proc. American Assoc. Cancer (22) Filed: Jul.
    [Show full text]
  • Chuanxiong Rhizoma Compound on HIF-VEGF Pathway and Cerebral Ischemia-Reperfusion Injury’S Biological Network Based on Systematic Pharmacology
    ORIGINAL RESEARCH published: 25 June 2021 doi: 10.3389/fphar.2021.601846 Exploring the Regulatory Mechanism of Hedysarum Multijugum Maxim.-Chuanxiong Rhizoma Compound on HIF-VEGF Pathway and Cerebral Ischemia-Reperfusion Injury’s Biological Network Based on Systematic Pharmacology Kailin Yang 1†, Liuting Zeng 1†, Anqi Ge 2†, Yi Chen 1†, Shanshan Wang 1†, Xiaofei Zhu 1,3† and Jinwen Ge 1,4* Edited by: 1 Takashi Sato, Key Laboratory of Hunan Province for Integrated Traditional Chinese and Western Medicine on Prevention and Treatment of 2 Tokyo University of Pharmacy and Life Cardio-Cerebral Diseases, Hunan University of Chinese Medicine, Changsha, China, Galactophore Department, The First 3 Sciences, Japan Hospital of Hunan University of Chinese Medicine, Changsha, China, School of Graduate, Central South University, Changsha, China, 4Shaoyang University, Shaoyang, China Reviewed by: Hui Zhao, Capital Medical University, China Background: Clinical research found that Hedysarum Multijugum Maxim.-Chuanxiong Maria Luisa Del Moral, fi University of Jaén, Spain Rhizoma Compound (HCC) has de nite curative effect on cerebral ischemic diseases, *Correspondence: such as ischemic stroke and cerebral ischemia-reperfusion injury (CIR). However, its Jinwen Ge mechanism for treating cerebral ischemia is still not fully explained. [email protected] †These authors share first authorship Methods: The traditional Chinese medicine related database were utilized to obtain the components of HCC. The Pharmmapper were used to predict HCC’s potential targets. Specialty section: The CIR genes were obtained from Genecards and OMIM and the protein-protein This article was submitted to interaction (PPI) data of HCC’s targets and IS genes were obtained from String Ethnopharmacology, a section of the journal database.
    [Show full text]
  • Limited Diagnostic Utility of Chromogranin a Measurements in Workup of Neuroendocrine Tumors
    diagnostics Article Limited Diagnostic Utility of Chromogranin A Measurements in Workup of Neuroendocrine Tumors Jonas Baekdal 1,2,*, Jesper Krogh 1,2, Marianne Klose 1,2, Pernille Holmager 1,2, Seppo W. Langer 1,3, Peter Oturai 1,4,5, Andreas Kjaer 1,4,5 , Birgitte Federspiel 1,6, Linda Hilsted 1,7, Jens F. Rehfeld 1,7, Ulrich Knigge 1,2,8 and Mikkel Andreassen 1,2 1 ENETS Neuroendocrine Tumor Centre of Excellence, Rigshospitalet, Copenhagen University Hospital, 2100 Copenhagen, Denmark; [email protected] (J.K.); [email protected] (M.K.); [email protected] (P.H.); [email protected] (S.W.L.); [email protected] (P.O.); [email protected] (A.K.); [email protected] (B.F.); [email protected] (L.H.); [email protected] (J.F.R.); [email protected] (U.K.); [email protected] (M.A.) 2 Department of Endocrinology, Rigshospitalet, Copenhagen University Hospital, 2100 Copenhagen, Denmark 3 Department of Oncology, Rigshospitalet, Copenhagen University Hospital, 2100 Copenhagen, Denmark 4 Department of Clinical Physiology, Nuclear Medicine & PET and Cluster for Molecular Imaging, Copenhagen University Hospital, 2100 Copenhagen, Denmark 5 Department of Biomedical Sciences, Rigshospitalet and University of Copenhagen, 2100 Copenhagen, Denmark 6 Department of Pathology, Rigshospitalet, Copenhagen University Hospital, 2100 Copenhagen, Denmark 7 Department of Clinical Biochemistry, Rigshospitalet, Copenhagen University Hospital, 2100 Copenhagen, Denmark 8 Department of Surgery and Transplantation, Rigshospitalet, Copenhagen University Hospital, 2100 Copenhagen, Denmark * Correspondence: [email protected]; Tel.: +45-6013-4687 Received: 11 October 2020; Accepted: 28 October 2020; Published: 29 October 2020 Abstract: Background: Plasma chromogranin A (CgA) is related to tumor burden and recommended in the follow-up of patients diagnosed with neuroendocrine tumors (NETs).
    [Show full text]
  • Anti-PSCA (Extracellular Domain) Polyclonal Antibody (DPAB1998RH) This Product Is for Research Use Only and Is Not Intended for Diagnostic Use
    Anti-PSCA (extracellular domain) polyclonal antibody (DPAB1998RH) This product is for research use only and is not intended for diagnostic use. PRODUCT INFORMATION Product Overview Rabbit anti-human prostate stem cell antigen polyclonal antibody is intended for qualitative immunohistochemistry with normal and neoplastic formalin-fixed, paraffin-embedded tissue sections, to be viewed by light microscopy. Clinical interpretation of st Antigen Description Prostate stem cell antigen is a protein that in humans is encoded by the PSCA gene. This gene encodes a glycosylphosphatidylinositol-anchored cell membrane glycoprotein. In addition to being highly expressed in the prostate it is also expressed in the bladder, placenta, colon, kidney, and stomach. This gene is up-regulated in a large proportion of prostate cancers and is also detected in cancers of the bladder and pancreas. This gene has a nonsynonymous nucleotide polymorphism at its start codon. Specificity This antibody reacts with a ~14 kD protein. Prostate Stem Cell Antigen (PSCA) is a cell surface antigen which is overexpressed in ~ 40% of primary prostate cancers and in nearly 100% of metastatic cancers. PSCA is also overexpressed in the majority of tra Immunogen A synthetic peptide derived from extracellular region of human PSCA protein. Isotype IgG Source/Host Rabbit Species Reactivity Human Conjugate Unconjugated Applications IHC Cellular Localization Cell membrane, cytoplasmic Positive Control Bladder carcinoma, prostate carcinoma Format Purified immunoglobulin fraction of rabbit
    [Show full text]
  • Small-Cell Neuroendocrine Tumors: Cell State Trumps the Oncogenic Driver Matthew G
    Published OnlineFirst January 26, 2018; DOI: 10.1158/1078-0432.CCR-17-3646 CCR Translations Clinical Cancer Research Small-Cell Neuroendocrine Tumors: Cell State Trumps the Oncogenic Driver Matthew G. Oser1,2 and Pasi A. Janne€ 1,2,3 Small-cell neuroendocrine cancers often originate in the lung SCCB and SCLC share common genetic driver mutations. but can also arise in the bladder or prostate. Phenotypically, Clin Cancer Res; 24(8); 1775–6. Ó2018 AACR. small-cell carcinoma of the bladder (SCCB) shares many simi- See related article by Chang et al., p. 1965 larities with small-cell lung cancer (SCLC). It is unknown whether In this issue of Clinical Cancer Research, Chang and colleagues ponent, suggesting that RB1 and TP53 loss occurs after the initial (1) perform DNA sequencing to characterize the mutational development of the urothelial carcinoma and is required for signature of small-cell carcinoma of the bladder (SCCB). They transdifferentiation from urothelial cancer to SCCB. This is rem- find that both SCCB and small-cell lung cancer (SCLC) harbor iniscent of a similar phenomenon observed in two other tumors near universal loss-of-function mutations in RB1 and TP53.In types: (i) EGFR-mutant lung cancer and (ii) castration-resistant contrast to the smoking mutational signature found in SCLC, prostate cancer, where RB1 and TP53 loss is necessary for the SCCB has an APOBEC mutational signature, a signature also transdifferentiation from an adenocarcinoma to a small-cell neu- found in urothelial carcinoma. Furthermore, they show that SCCB roendocrine tumor. EGFR-mutant lung cancers acquire RB1 loss as and urothelial carcinoma share many common mutations that are a mechanism of resistance to EGFR tyrosine kinase inhibitors (3), distinct from mutations found in SCLC, suggesting that SCCB and castration-resistant prostate cancers acquire RB1 and TP53 may arise from a preexisting urothelial cancer.
    [Show full text]
  • REVIEW ARTICLE the Genetics of Autism
    REVIEW ARTICLE The Genetics of Autism Rebecca Muhle, BA*; Stephanie V. Trentacoste, BA*; and Isabelle Rapin, MD‡ ABSTRACT. Autism is a complex, behaviorally de- tribution of a few well characterized X-linked disorders, fined, static disorder of the immature brain that is of male-to-male transmission in a number of families rules great concern to the practicing pediatrician because of an out X-linkage as the prevailing mode of inheritance. The astonishing 556% reported increase in pediatric preva- recurrence rate in siblings of affected children is ϳ2% to lence between 1991 and 1997, to a prevalence higher than 8%, much higher than the prevalence rate in the general that of spina bifida, cancer, or Down syndrome. This population but much lower than in single-gene diseases. jump is probably attributable to heightened awareness Twin studies reported 60% concordance for classic au- and changing diagnostic criteria rather than to new en- tism in monozygotic (MZ) twins versus 0 in dizygotic vironmental influences. Autism is not a disease but a (DZ) twins, the higher MZ concordance attesting to ge- syndrome with multiple nongenetic and genetic causes. netic inheritance as the predominant causative agent. By autism (the autistic spectrum disorders [ASDs]), we Reevaluation for a broader autistic phenotype that in- mean the wide spectrum of developmental disorders cluded communication and social disorders increased characterized by impairments in 3 behavioral domains: 1) concordance remarkably from 60% to 92% in MZ twins social interaction; 2) language, communication, and and from 0% to 10% in DZ pairs. This suggests that imaginative play; and 3) range of interests and activities.
    [Show full text]