Immunological Implications and Molecular Diagnostics of Genitourinary Cancer

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Immunological Implications and Molecular Diagnostics of Genitourinary Cancer updates on recent accomplishments, unifying concepts, and future challenges in the study of tumor-associated immune cells, emphasizing genitourinary cancers. The presence of inflammatory immune cells in human tumors raise a fundamental question: How do cancer cells avoid destruction by immune attack? In principle, tumor development can be controlled by cytotoxic innate and adaptive immune cells, however, as tumors develop from neoplastic tissue to clinically detectable tumors, cancer cells evolve different mechanisms. This book covers research on the immunological implications of genitourinary cancer with a comprehensive view, especially surrounding diagnosis and cellular mechanisms. Front Cover Immunological Implications and Molecular Diagnostics of Genitourinary Cancer Copyright Page Contents List of contributors About the editor Preface Acknowledgments Editorial advisory board Editorial management committee 1 Introduction to the molecular aspects and viral therapy of genitourinary tumors 1.1 Background References 2 Liquid biopsy of exosome markers for molecular diagnosis of genitourinary cancer 2.1 Introduction 2.2 Tissue biopsy versus liquid biopsy 2.3 Renal cell cancer 2.4 Bladder cancer 2.5 Prostate cancer 2.6 Conclusion References 3 The molecular mechanism of novel oncogenes dysregulating signaling pathways associated with cervical carcinoma 3.1 Introduction 3.2 Cervical cancer overview 3.2.1 Epidemiology of cervical cancer 3.2.2 Anatomopathology of the cervix 3.2.3 The different cancers of the cervix 3.2.4 Risk factors of cervical cancer 3.3 The leading oncogenes related to cervical cancer development 3.3.1 Calponin 3 3.3.2 Antisilencing function 1B 3.3.3 Long noncoding RNA colorectal neoplasia differentially expressed 3.3.4 Proline-rich Protein 11 3.4 Conclusion Acknowledgment References 4 Role of epigenetic factors in cancer progression induced by inactivation of tumor suppressors genes 4.1 Introduction 4.2 Methylation of DNA 4.3 Histone code 4.4 The microRNAs 4.5 Conclusion Acknowledgment References 5 Exosomes as diagnostic and prognostic tools in prostate cancer 5.1 Introduction 5.2 Structure, biogenesis, and function of exosomes 5.2.1 Structure and biogenesis of exosomes 5.2.2 Functions of exosomes 5.3 The functional roles and tumor-derived exosomes in prostate cancer progression 5.3.1 The diagnosis potential of exosomes in prostate cancer 5.3.2 Future directions and applications of exosomes in prostate cancer Acknowledgments References 6 Adenovirus vectors for vaccination and cancer gene therapy 6.1 Introduction 6.2 Several approaches to overcome problems associated with the targeting of adenoviruses 6.3 General properties of adenovirus and adenovirus vector 6.4 Adenovirus tumor-selective replication 6.5 Genetic modification to alter transfection range of adenoviruses 6.5.1 1-Insertion of foreign ligand into fiber protein 6.5.2 2-Fiber mutation for generating targeted adenoviruses 6.5.3 3-Fiber exchange 6.5.4 4-Modification of other capsid proteins 6.6 Conclusion Acknowledgment References 7 Molecular diagnosis of human oncogenic viruses associated with prostate cancer: Human Papillomavirus and Epstein–Barr virus 7.1 Introduction 7.2 Molecular epidemiology of human papillomavirus and Epstein–Barr virus associated with prostate cancer worldwide 7.2.1 Prostate cancer 7.2.2 Human papillomavirus and prostate cancer 7.2.3 Epstein–Barr virus 7.2.4 Human papillomavirus and Epstein–Barr virus coinfection 7.3 Molecular diagnosis and prognostic biomarkers of prostate cancer 7.3.1 Blood biomarkers 7.3.1.1 Prostate-specific antigen 7.3.1.2 Prostate health index 7.3.1.3 4Kscore 7.3.1.4 Serum protein panel 7.3.2 Urinary biomarker 7.3.2.1 PCa antigen 7.3.2.2 Fusion TMPRSS2-ERG 7.3.3 Tissue biomarker 7.3.3.1 PTEN gene 7.3.3.2 ConfirmMDx 7.3.3.3 Oncotype DX Genomic Prostate Score 7.3.3.4 ProMark 7.3.4 Exosomes as a diagnostic and prognostic tool for prostate 7.3.4.1 Exosomal biomarkers 7.3.4.2 Cellular factors promoting the emergence and development of tumors via exosomes in cells infected with Epstein–Barr... 7.4 Conclusion References 8 Molecular characterization of oncogenic biomarkers associated with genitourinary cancers: the case of prostate cancer 8.1 Introduction 8.2 General information about prostate cancer 8.2.1 Definition 8.2.2 Carcinogenesis 8.2.3 Tumor development 8.2.4 Epidemiology of prostate cancer 8.2.4.1 Epidemiology of prostate cancer on a global scale 8.2.4.2 Epidemiology of prostate cancer in Africa 8.2.4.3 Epidemiology of prostate cancer in Morocco 8.3 Tumor development 8.3.1 Risk factors for prostate cancer 8.3.1.1 Family history 8.3.1.2 Hormonal and other growth factors 8.3.1.2.1 Androgens 8.3.1.2.2 Vitamin D and its receptor 8.3.1.2.3 Insulin growth factor 1 8.3.1.3 Environmental factors: diet and other factors 8.3.1.3.1 Foods at risk 8.3.1.3.2 Protective foods 8.3.1.4 Other factors 8.3.2 Genetic mutations responsible for prostate cancer 8.3.2.1 HOXB13 variants 8.3.2.2 Mutations in the BRAF gene 8.4 Methods for studying genetic polymorphisms 8.4.1 Classical genotyping methods 8.4.1.1 High-throughput genotyping 8.4.1.1.1 Spoligotyping 8.4.1.2 VNTR typing 8.4.1.3 Double-repetitive-element-polymerase chain reaction 8.4.1.4 Biochips, multiparametric biosensors 8.4.1.4.1 Biosensors 8.4.1.5 DNA chips and oligonucleotide chips 8.4.1.6 Protein chips 8.5 Conclusion Acknowledgments References 9 Diagnostic screening of the microdeleation mutations in the azoospermia factor-gene cluster of the Y chromosome and; pros... 9.1 Background for our hypothesis on the azoospermia factor gene cluster among Arabs for future gene therapy of infertility 9.2 Landscape of the azoospermia factor gene cluster and chromosome Y chromosome structure 9.3 Global heterogeneity and ethnicity of familial infertility clustering of azoospermia factor microdeletion variants amon... 9.4 Familial infertility clustering and consanguinity among Arabian populations 9.5 Diagnostic criteria and medical conditions as set by WHO criteria for infertility diagnosis 9.6 Types of microdeletions in the azoospermia factor gene cluster of Y chromosome 9.7 Genetic diagnosis of azoospermia factor microdeletion by multiplex polymerase chain reaction technology 9.7.1 Clinical conditions 9.7.2 Multiplex polymerase chain reaction protocol to be used in diagnosis of the azoospermia factor microdeletions of Y ch... 9.7.3 Ethical criteria and consideration adopted for blood samples and YDNA 9.7.4 Clinical criteria and the practical cut-off value for azoospermia factor testing 9.7.5 Practical recommendations for inclusion criteria and stratification of Azoospermia 9.7.6 Commercial kits available in the market to be used 9.7.6.1 Promega kit for DNA extraction from blood samples 9.7.6.2 Devyser azoospermia factor 2 for azoospermia factor microdeletion detection 9.8 Influence of the use of in vitro fertilization technology 9.9 Gene therapy application of azoospermia factor gene in different genealogical lineages of the Y-chromosome References 10 Recent advances in high-risk human papillomavirus genotype relationship with bladder cancer tumor genesis 10.1 Introduction 10.2 Human papillomaviruses 10.3 Epidemiology of bladder cancer 10.4 Global prevalence of human papillomavirus in bladder cancer 10.4.1 Prevalence of high-risk human papillomavirus by histological type 10.4.1.1 Transitional cell carcinoma or urothelial carcinoma 10.4.1.2 Squamous cell carcinomas 10.4.1.3 Other histological types of bladder cancer 10.5 Recent evidence for high-risk human papillomavirus involvement in bladder cancer 10.5.1 Integration of human papillomavirus DNA 10.5.2 Human papillomavirus and p16 overexpression status in bladder cancer 10.5.3 Pathological clinical course 10.5.3.1 Passage of a guard and upper stage 10.5.3.2 Human papillomavirus status and bladder cancer recurrence 10.6 Detection of human papillomavirus infection in bladder cancer 10.7 Human papillomavirus treatment and prevention 10.8 Conclusion References 11 Tumor-associated macrophages in prostate cancer: role in progression and therapy 11.1 Introduction 11.2 Prostate cancer initiation, progression, and immunity 11.3 Cancer and macrophage 11.4 Tumor-associated macrophages and prostate cancer 11.4.1 Prostate cancer progression and tumor-associated macrophage 11.4.2 Tumor-associated macrophages as mediators of immunosuppression in prostate cancer 11.4.3 Prostate cancer stem cells and tumor-associated macrophage 11.4.4 Tumor-associated macrophages and angiogenesis in prostate cancer 11.4.5 Role of tumor-associated macrophages in Extracellular matrix (ECM) remodeling, invasion, and metastasis 11.4.6 Chemo- and radio-resistance in prostate cancer and tumor-associated macrophage 11.4.7 Therapeutic implication of macrophages in prostate cancer 11.4.8 Macrophage-mediated prostate cancer cytotoxicity 11.4.8.1 Regulation of macrophage polarization 11.4.8.2 Strategies modulating macrophage recruitment 11.4.8.3 Inhibitory strategies against tumor-associated macrophage 11.4.8.4 Gene modification in macrophage 11.5 Conclusion Acknowledgment References 12 Emerging therapeutic targets of genitourinary tumors 12.1 Introduction 12.2 PD-1 12.3 Von Hippel–Lindau tumor suppressor/HIF2-vascular endothelial growth factor 12.4 Vascular endothelial growth factor receptor 12.5 Indoleamine-2,3-dioxygenase 12.6 Androgen receptor 12.7 Conclusion References 13 Cell–cell differentiation induction: model for cervical cancer 13.1 Introduction 13.2 Cervical cancer 13.2.1 Epidemiology of cervical cancer 13.2.2 Anatomopathology of the cervix 13.2.3 Risk factors of cervical cancer 13.3 Overview of cellular differentiation 13.3.1 Principle of cell differentiation 13.3.1.1 Universal cell differentiation markers 13.3.1.2 Specific cell differentiation markers 13.3.2 Correlation between cell growth and cell differentiation 13.3.3 Cellular models for the study of proliferation and differentiation 13.3.3.1 Myoblasts 13.3.3.2 Differentiation of myoblasts 13.3.4 Virus interaction and cell proliferation/differentiation 13.4 Cell differentiation study methods 13.5 Tumor differentiation: case of cervical cancer 13.5.1 Generality of tumor differentiation 13.5.2 Cell differentiation of cervical carcinoma 13.6 Conclusion Acknowledgment References 14 The clinical significance of long noncoding RNAs expression in cervical cancers 14.1 Introduction 14.2 Long noncoding RNAs as potential biomarker candidates 14.2.1 Long noncoding RNAs s as biomarkers for screening of cervical cancer 14.3 Long noncoding RNAs as biomarkers for diagnosis and early detection of cervical cancers 14.4 Long noncoding RNAs as biomarkers of prognosis and survival 14.5 Long noncoding RNAs in cervical cancer treatment and therapy 14.5.1 Long noncoding RNAs in resistance to treatment of cervical cancer 14.5.2 Long noncoding RNAs in cervical cancer therapy 14.6 Conclusions Acknowledgment References 15 Triple-negative breast cancer and its correlation with viral agents 15.1 Introduction 15.2 Breast cancer presentation 15.2.1 Histological types of breast cancer 15.2.1.1 Ductal carcinoma in situ 15.2.1.2 Lobular carcinoma in situ 15.2.1.3 Invasive ductal carcinoma 15.2.1.4 Invasive lobular carcinoma 15.2.1.5 Metaplastic carcinoma 15.2.1.6 Inflammatory breast cancer 15.2.1.7 Metastatic breast cancer 15.2.2 Stages of breast cancer 15.2.3 Molecular types of breast cancer 15.3 A focus on triple-negative breast cancer 15.4 Risk factors associated with triple-negative breast cancer 15.5 Implications of viral agents in triple-negative breast cancer 15.6 The special case of triple-negative breast cancer 15.7 Treatment modalities of triple-negative breast cancer 15.7.1 Current treatment strategies and limitations 15.8 Natural anticancer agents in triple-negative breast cancer 15.9 Conclusion Acknowledgments References 16 Role of exosomes in bladder cancer diagnosis and therapy 16.1 Introduction 16.2 Exosomes: nanovesicles of endosomal origin 16.2.1 Exosome heterogeneity 16.2.2 Functions of exosomes 16.2.3 Roles of exosomes in bladder cancer 16.3 Urinary biomarkers for bladder cancer diagnosis 16.3.1 Exosomes therapy applications for bladder cancers 16.4 Conclusions Acknowledgments References 17 Upper urinary tract urothelial cell carcinoma 17.1 Introduction 17.2 Epidemiology 17.2.1 Frequency 17.2.2 Age 17.2.3 Sex 17.2.4 Risk factors—ethiopathogenesis 17.2.4.1 Tobacco 17.2.4.2 Occupational origin 17.2.4.2.1 Aromatic amines 17.2.4.2.2 Chlorinated solvents 17.2.4.3 Drug origin 17.2.4.3.1 Abuse of analgesics (phenacetin) 17.2.4.3.2 Cyclophosphamide and ifosfamide 17.2.4.4 Heredity 17.2.4.5 Other factors 17.2.4.5.1 Lithiasis 17.2.4.5.2 Urinary tract infections 17.2.4.5.3 Aristolochic acid nephropathy (Balkan endemic nephropathy and Chinese herbal nephropathy) 17.2.4.5.4 Blackfoot disease 17.2.4.6 History of bladder tumor: in 20%–30% of patients with upper tract urothelial carcinomas 17.2.4.6.1 Anatomopathology 17.2.4.7 Clinical 17.2.4.7.1 Circumstances of discovery 17.2.4.8 Paraclinical 17.2.4.8.1 Imaging 17.2.4.8.2 Endoscopy 17.2.4.9 Preoperative prognostic factors 17.2.4.10 Treatment 17.2.4.10.1 Localized upper tract urothelial carcinomas High-risk upper tract urothelial carcinomas 17.2.4.10.2 Metastatic disease 17.3 Surveillance References 18 Testicular cancer 18.1 Introduction 18.2 Clinical presentation 18.3 Investigations 18.3.1 Serum tumor markers 18.3.2 Imagery 18.3.2.1 Scrotal doppler 18.4 Abdomino-pelvic and thoracic imaging 18.5 Surgical management 18.6 Retroperitoneal lymphadenectomy for staging 18.7 Treatment after RPLND or residual mass resection References 19 A comprehensive survey on spectrum of BRCA1 and BRCA2 pathogenic variants in breast and ovarian cancer 19.1 Introduction 19.2 BRCA1 19.3 BRCA2 19.4 BRCA-associated breast and ovarian cancer 19.5 BRCA1 and BRCA2 genes mutations in breast and/or ovarian cancer 19.6 BRCA1 and BRCA2 recurrent/founder variants in North Africa 19.7 BRCA1 and BRCA2 recurrent/founder variants worldwide 19.8 BRCA1- and BRCA2-specific variants in North Africa and Worldwide References 20 Molecular and epidemiological characterization of bladder tumors 20.1 Introduction 20.2 Anatomy of the urinary system 20.2.1 Kidneys 20.2.2 Urinary tract 20.2.3 Bladder 20.3 Bladder cancer 20.3.1 Epidemiology 20.3.2 Risk factors for bladder cancer 20.3.3 The diagnosis 20.4 Six-molecular characterization of bladder tumors 20.4.1 Point mutations 20.4.1.1 RAS family genes 20.4.1.2 The FGFR3 gene 20.4.1.3 The p53 gene 20.5 Chromosomal aberrations 20.5.1 Epigenetic aberrations 20.6 Conclusion Acknowledgments References 21 Impact of signaling in the development pathway of genitourinary cancers 21.1 Introduction 21.2 General principles of cell signaling 21.3 Impact of androgen receptor alterations on signaling pathways related to cell differentiation and prostate cancer prog... 21.3.1 Androgen receptor 21.3.1.1 Genomic signaling pathway of the androgen receptor 21.4 Oncogenic alterations 21.4.1 Sphingosine kinase 1/sphingosine 1-phosphate 21.4.1.1 The sphingosine kinase 1/sphingosine 1-phosphate signaling pathway 21.5 Oncogenic alterations 21.5.1 Bone metastases of prostate cancer 21.6 Growth factor signaling pathway 21.7 Oncogenic alterations 21.7.1 Phosphatidylinositol-3-kinase 21.7.1.1 Phosphatidylinositol-3-kinase signaling pathway 21.8 Oncogenic alterations 21.9 Conclusion 21.10 Acknowledgments References 22 Prostate cancer: genetic changes and viral-mediated immune regulation 22.1 Introduction 22.2 Epidemiology of prostate cancer 22.3 Viruses associated with prostate cancer 22.3.1 Human papillomavirus 22.3.2 Herperviruses 22.3.3 BK 22.3.4 XMRV 22.4 Carcinogenesis of the prostate: interaction between host genetics and viral infection 22.5 Viral-mediated immune deregulation 22.5.1 RNASEL (Ribonuclease L) 22.5.2 Toll-like receptors 22.5.2.1 Macrophage inhibitory cytokine 1 22.5.2.2 Interleukin-1 receptor antagonist 22.5.3 Other genes linked to inflammation 22.6 Conclusion Acknowledgment References 23 Dramatic impact of partial loss of PTEN function on tumorigenesis and progression of prostate cancer 23.1 Introduction 23.1.1 Gross Anatomical Features 23.1.1.1 The prostatic epithelium 23.1.1.2 Epithelial cells 23.1.1.3 Neuroendocrine cells 23.1.1.4 Basal cells 23.1.1.5 The prostatic stroma 23.2 Epidemiology 23.3 The PI3K/Akt signaling pathway 23.4 Changes in PTEN activity in health and disease 23.5 Posttranscriptional regulation of PTEN by noncoding RNAs 23.6 Posttranslational modification: phosphorylation 23.7 Posttranslational modification: ubiquitination 23.8 Other ubiquitin-like modifications: SUMOylation and ISGylation 23.8.1 Posttranslational modification: oxidation 23.8.2 Posttranslational modification: acetylation 23.9 PTEN loss in prostate cancer 23.9.1 Tumor PTEN affects immune infiltration 23.9.2 Various genetic aberrations in the PI3K-AKT-mTOR pathway in prostate cancer 23.10 Conclusion Acknowledgment References 24 Association between glucose consumption and cancer development: prostate cancer and bladder cancer 24.1 Introduction 24.2 Glycose metabolism 24.2.1 General scheme of dietary carbohydrate assimilation 24.2.2 Carbohydrate catabolism 24.2.3 Glycolysis (or Embden–Meyerhof pathway) 24.3 Regulation of glucose metabolism in cancer cells 24.3.1 Activation of hypoxia-inducible factor drives increased glycolysis 24.3.2 Glucose consumption in prostate cancer 24.3.3 Metabolic mechanisms in prostate cancer 24.3.3.1 PGC-1α and glucose metabolism 24.3.3.2 PGC-1α in prostate cancer 24.3.4 Androgens reprogram prostate cancer cell metabolism 24.3.5 Glucose consumption in bladder cancer 24.3.6 Metabolic mechanisms in bladder cancer 24.4 Conclusion Acknowlegment References 25 Oncogenic human viruses associated with prostate cancer: molecular epidemiology of Human Papillomavirus and Epstein–Barr... 25.1 Introduction 25.1.1 History, taxonomy, and classification of human papillomavirus and Epstein–Barr virus 25.2 Molecular epidemiology of human papillomavirus and Epstein–Barr virus associated with prostate cancer worldwide 25.2.1 Epidemiology of prostate cancer worldwide 25.2.2 Human papillomavirus and prostate cancer 25.2.3 Epstein–Barr virus 25.2.4 Epidemiology of human papillomavirus and Epstein–Barr virus coinfection 25.3 Implications and associations of human papillomavirus and Epstein–Barr virus prostate cancer 25.3.1 Coinfection of human papillomavirus and Epstein–Barr virus 25.4 Conclusion References 26 Genitourinary cancers immune biomarkers: a comprehensive overview 26.1 Introduction 26.2 Immune response in urogenital cancers 26.3 Immunotherapy of urogenital cancers 26.3.1 Checkpoint’s inhibitors 26.3.1.1 Anti-PD-1/ anti-PD-L1 26.3.1.2 Anti-cytotoxic T lymphocyte-associated protein 4 antibodies 26.3.2 Bacillus Calmette–Guerin 26.3.3 Monoclonal antibodies 26.3.4 Combined Therapies 26.3.5 Other therapies 26.3.6 Perspectives 26.3.7 Alternative therapies 26.4 Prostate and bladder cancers biomarkers 26.5 Renal cell carcinoma biomarkers 26.5.1 Pathologic and molecular subtypes of renal cell carcinoma 26.5.1.1 Kidney cancer biomarkers 26.5.1.1.1 Single-nucleotide polymorphisms 26.5.1.2 MicroRNA 26.5.1.3 The change in the DNA 26.5.1.4 DNA methylation 26.6 Recent trends in antitumor vaccines References 27 The global genomic allelic heterogeneity of the HOXB 13 variants of prostate cancer and gene therapy application for dif... 27.1 Introduction 27.2 Background and hypothesis on the prostate cancer allelic heterogeneity associated with the genealogical lineages of po... 27.3 The landscape of the HOXB 13 gene cluster on chromosome 17 27.4 The landscape of the Short tandem repeat microsatellite on the nonrecombined region of the Y-chromosome 27.4.1 Characteristics of the short tandem repeat microsatellites of Y-chromosome and its application in human ancestry and... 27.4.2 Application of the Y-short tandem repeats in human ancestry and different genealogical lineages 27.4.3 Global studies on short tandem repeat of different genealogical lineages of ancestry 27.5 Global allelic heterogeneity of the HOXB 13 variants of prostate cancer among different genealogical lineages of popul... 27.6 Practices on the genetic diagnosis of the haplotypes of microsatellite short tandem repeats and the haplogroups of gen... 27.6.1 Human genomic DNA extraction and purification 27.6.2 Protocol optimization details for short tandem repeats analysis are as follows 27.6.3 Quality control and DNA purity 27.6.4 Protocol optimization for DNA amplification polymerase chain reaction 27.6.5 Genotyping of the short tandem repeat alleles on genetic analyzer and data analysis 27.6.5.1 World Health Organization online data on the global prevalence of prostate cancer 27.7 Practices on the genetic diagnosis of prostate cancer 27.7.1 Genotyping of the Y-chromosome short tandem repeats and haplogroup lineage prediction 27.7.2 Data deposition and availability in the international gene/banks 27.8 Gene therapy applications and future challenges against prostate cancer in different ethnicities of Y-chromosome References 28 Impact of vitamin D status on breast cancer prognosis 28.1 Introduction 28.2 Vitamin D 28.2.1 Intakes of vitamin D 28.2.2 Vitamin D metabolism 28.2.3 Target cells 28.3 Vitamin D and breast cancer relationship 28.3.1 Vitamin D pathophysiology and link to cancer 28.3.2 Sun exposure and breast cancer relationship 28.3.3 Link between vitamin D-rich diet and breast cancer 28.3.4 Vitamin D supplementation and breast cancer relationship 28.3.5 Link between total vitamin D intake and breast cancer 28.3.6 Link between serum 25(OH)D and breast cancer 28.4 Vitamin D and breast cancer prognosis 28.4.1 Vitamin D and local breast cancer recurrence 28.4.2 Vitamin D and metastatic spread of breast cancer 28.4.3 Breast cancer survival and vitamin D 28.4.4 Prognosis of vitamin D and breast cancer by hormonal status (menopausal and nonmenopausal) 28.4.4.1 Postmenopausal women 28.4.4.2 Women in premenopause 28.4.5 Vitamin D and breast cancer prognosis by tumor hormone receptor status 28.5 Conclusion References Index Back Cover