Biology and Molecular Markers of Malignant Gonadal Germ Cell Tumors
نویسندگان
چکیده
5 Original Publications 8 Abbreviations 9 Introduction 10 Review of the Literature 11 1. Germ cells 11 1.1 Inner cell mass and embryonic stem cells 11 1.2 Factors essential for maintenance of pluripotency and self-renewal 11 1.3 Development and migration of germ cells 14 2. Gonadal development 16 2.1 Ovarian differ entiation 17 2.2 Testicular differentiation 18 3. GATA transcription factors in gonadal development and physiology 19 4. Estrogen receptors in gonadal development and physiology 21 5. Gonadal Germ Cell Tumors 23 5.1 Germ cell tumor development 24 5.2 Testicular dysgenesis syndrome 25 5.3 Clinicopathological characteristics of gonadal germ cell tumors 26 5.4 Serum and tissue tumor markers 26 5.5 Treatment and survival of gonadal germ cell tumor patients 28 Aims of the Study 29 Patients, Samples and Methods 29 1. Malignant ovarian germ cell tumor patients (I, II, III) 30 2. Tissue samples (I–V) 30 2.1. Human malignant ovarian germ cell tumor samples 30 2.2. Human fetal testicular, testicular CIS and tumor samples 30 3. Human germinoma-derived cell line (II, III, V) 31 4. Immunohistochemistry (I–IV) 31 5. Western blotting (V) 32 6. Semi-quantitative RT-PCR (III, V) 32 7. Stimulation of NCC-IT cells with estradiol (III) 33 8. Cell transfection and siRNA (V) 33 9. Flow cytometric analysis (III, V) 33 10. Statistical analysis (II, III) 34 Results and Discussion 34 1. Biology of gonadal germ cell tumors 34 1.1 Pluripotency and self-renewal in ovarian germ cell tumors (II, IV) 34 1.2 CIS and fetal origin of testicular germ cell tumors (IV) 35 1.3 Function of GATA-4 in fetal testicular and CIS cells (IV) 37 1.4 Estrogen signalling pathway in MOGCTs (III, V) 38 2. Diagnosis and prognosis of gonadal germ cell tumors 40 2.1 Diagnostic tools for gonadal germ cell tumors (I, II, IV) 40 2.2 Prognostic tools for malignant ovarian germ cell tumors (II) 42 3. Clinical significance of the studies 44 Conclusions and Future Perspectives 44 1.1 Conclusions 44 1.2 Future perspectives 45 Acknowledgments 46 References 47
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