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An accurate, inexpensive, and noninvasive method for the early diagnosis of cancer has been something of a holy grail among cancer researchers, but until recently a method meeting all three criteria has been elusive. Nucleic acids were first discovered in circulation in 1948, but it was not until the 1960s and 70s that patients with autoimmune disease and cancer were discovered to have higher levels of circulating DNA than were detected in in healthy persons.
The focus in this volume is on three major applications of the circulating nucleic acids detection method: cancer, fetal medicine, and diseases such as diabetes, stroke, and myocardial infarction. In addition, there are reports on the biology and origins of circulating DNA and RNA and on improved methods for the detection of nucleic acids in plasma and serum.
The circulating DNA found in cancer patients has many characteristics in common with their tumors, which made it an attractive candidate for use in the diagnosis and management of patients with malignancies. This method can also be applied to the assessment of the sublinical tumor burden in cancer patients, thus reducing the risk of unnecessary chemotherapy.
Detection of nucleic acids circulating in maternal serum means that fetal diagnosis may be possible without resorting to the more dangerous and invasive methods now used (e.g., amniotic fluid and chorionic villus sampling). Detection of problems in the pregnancy such as preeclampsia and intrauterine growth retardation may also become possible through maternal blood samples.
In diabetic patients, circulating nucleic acids can be used for the early detection of developments such as retinopathy.
The benefits of using circulating nucleic acids in the diagnosis and management of cancer and chronic disease will be realized through earlier detection by means of this less expensive and less invasive testing technique and through its potential for closer monitoring of the disease.
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Welcoming Remarks: P. Whitfield.
Circulating Nicleic Acids in Plasma and Serum Recent Developments: R. Swaminathan and Asif N. Butt.
Part I: Biology of Circulating Nucleic Acids:.
1. Prehistory of CNAPS, the Birth of a Hypothesis: Circulating DNA.: Maurice Stroun and Philippe Anker.
2. Circulating DNA- Intra-Cellular and Intra-Organ Messenger?: P. B. Gahan.
3. Immunological Aspects of Circulating DNA: Philippe Anker And Maurice Stroun.
4. Biology of Circulating Mrna – Still More Questions Than Answers: Michael Fleischhacker.
5. Investigation of the Origin of Extracellular RNA in Human Cell Culture: Katrin Bottcher, Alexander Wenzel And Jens M. Warnecke.
6. Hypoxia-Induced Membrane-Bound Apoptotic DNA Particles: Potential Mechanism of Fetal DNA in Maternal Plasma: Aaron F. Orozco, Farideh Z. Bischoff, Cassandra Horne, Edwina Popek, Joe Leigh Simpson And Dorothy E. Lewis.
Part II: Fetal Nucleic Acids:.
7. Fetal Nucleic Acids in Maternal Body Fluids: an Update: Diana W. Bianchi, Tuangsit Wataganara, Olav Lapaire, May Lee Tjoa, Jill L. Maron, Paige B. Larrabee And Kirby L. Johnson.
8. Fetal DNA in Maternal Plasma: Progress Through Epigenetics: Y. M. Dennis Lo.
9. Cell-Free DNA in Maternal Plasma: Is It a Question of Size?: Ying Li, Wolfgang Holzgreve, Edoardo Di Naro, Angeloantonio Vitucci, And Sinuhe Hahn.
Fetal Blood Group Genotyping: Present and Future: Geoff Daniels, Kirstin Finning, Pete Martin And Jo Summers.
10. Placental RNA in Maternal Plasma: Towards Non-Invasive Fetal Gene Expression Profiling: Nancy B. Y. Tsui And Y. M. Dennis Lo.
11. Development and Application of a Real Time Quantitative PCR for Prenatal Detection of Fetal O-Thalassemia From Maternal Plasma.
Warunee Tungwiwat, Supan Fucharoen, Goonnapa Fucharoen, Thawalwong Ratanasiri And Kanokwan Anchaisuriya.
12. Detection of a Paternally Fetal Mutation in Maternal Plasma by the Use of Automatic Sequencing: Ana Bustamante-Aragones, Maria Garcia-Hoyos, Marta Odriguez De Alba, Cristina Gonzalez-Gonzalaz, Isabel Orda-Sanchez, Dan Diego-Alvarez, M. Jose Trujillo-Tiebas, Armen Ayuso And Carmen Ramos.
13. Occurrence of Neutrophil Extracellular DNA Traps (Nets) in Pre-Eclampsia: a Link with Elevated Levels of Cell-Free DNA?: Anurag Gupta, Paul Hasler, Stephen Gebhardt, Wolfgang And Sinuhe Hahn.
14. Use of Bi-Allelic Insertion/Deletion Polymorphisms As a Positive Control for Fetal Genotyping in Maternal Blood: First Clinical Experience: Godelieve Cml Page-Christiaens, Bernadette Bossers, C. Ellen Van Der Schoot, Masja De Haas.
15. PLAC1 Mrna in Maternal Blood Correlates with Doppler of Uterine Arteries Waveform in Normal Pregnancies At 2nd and 3rd Trimester: Antonio Farina, Manuela Concu, Irina Banzola, Annalisa Tempesta,Sonia Vagnoni, Sandro Gabrielli, Mara Mattioli, Paolo Carinci, Gianluigi Pilu, Danila Morano, Nicola Rizzo.
16. Different Approaches for Non-Invasive Prenatal Diagnosis of Genetic Diseases Based On PNA-Mediated Enriched PCR: Galbiati Silvia, Restagno Gabriella, Foglieni Barbara, Bonalumi Sara, Travi Maurizio, Piga Antonio, Sbaiz Luca, Chiari Marcella, Damin Francesco Smid Maddalena, Valsecchi Luca, Pasi Federica, Ferrari And Laura Cremonesi.
17. Detection of Snps in the Plasma of Pregnant Women and in the Urine of Kidney Transplant Recipients by Mass Spectrometry: Ying Li, Deidre Hahn, Friedel Wenzel, Wolfgang Holzgreve And Sinuhe Hahn.
18. Non-Invasive Prenatal Diagnostic Assay for the Detection of -Thalassaemia: Thessalia Papasavva, Gabriel Kalakoutis, Ioannis Kalikas, Lectra Noekli, Soteroula Papacharalambous, Andreanni Yrri And Marina Kleanthous.
Part III: Nucleic Acids and Cancer:.
19. Circulating DNA and Lung Cancer: Xiaoyan Xue, Yong M. Zhu And Penella J. Woll.
20. Circulating Nucleic Acids in Plasma/Serum and Tumour Progression: Are Apoptotic Bodies Involved? an Experimental Study in a Rat Cancer Model: Julia Samos, Dolores C. García-Olmo, Maria G. Picazo, Antonio Rubio-Vitaller And Damian Garcia-Olmo.
21. Plasma RNA Integrity Analysis: Methodology and Validation: Blenda C. K. Wong And Y. M. Dennis Lo.
22. Molecular Diagnostic Markers for Lung Cancer in Sputum and Plasma: Yi-Ching Wang, Han-Shui Hsu, Tsz-Pei Chen And Jung-Ta Chen.
23. Quantitative Analysis of Plasma DNA in Colorectal Cancer Patients: a Novel Prognostic Tool: Milo Frattini, Gianfrancesco Gallino, Stefano Signoroni, Debora Balestra. Luigi Battaglia, Gabriella Sozzi, Ermanno Leo, Silvana Pilotti And Marco A. Pierotti.
24. Circulating DNA and DNAse Activity in Human Blood: Svetlana N. Tamkovich, Anna V. Cherepanova, Elena Yu. Rykova, Dmitrii V. Pyshnyi, Valentin V. Vlassov And Pavel P. Laktionov.
Comparative Analysis of Mesenteric and Peripheral Blood Circulating Tumour DNA in Colorectal Cancer Patients: Bret Taback, Sukamal Saha And Dave S. B. Hoon.
25. Real Time Quantification of Human Telomerase Reverse Transcriptase Mrna in the Plasma of Patients with Prostate Cancer: F. Dasí, P. Martinez-Rodes, J. a. March, J Santamaria, J. M. Martinez-Javaloyas, M Gil and S. F. Alino.
26. Epigenetic Analysis of Body Fluids and Tumour Tissues: Application of a Comprehensive Molecular Assessment for Early Stage Breast Cancer Patients: Bret Taback, Armando E. Giuliano, Ron Lai, Nora Hansen, Frederick R. Singer, Klaus Pantel and Dave S. B. Hoon.
27. Comparison of Genetic Alterations Detected in Circulating Microsatellite-DNA in Blood Plasma Samples of Patients with Prostate Cancer and Benign Prostatic Hyperplasia: Imke Müller, Karoline Urban, Klaus Panel and Heidi Schwarzenbach.
28. Quantification of Total Plasma Cell-Free DNA in Ovarian Cancer Using Real Time PCR: Aparna A. Kamat, Anil K. Sood, Dianne Dang, David M. Gershenson, Joe L. Simpson and Farideh Z. Bischoff.
29. Cell-Free DNA and RNA in Plasma As a New Molecular Marker for Prostate and Breast Cancer: Eirini Papadopoulou, Elias Davilas, Vasilios Sotiriou, Eleftherios Georgakopoulos, Stravroula Georgakopoulou, Alexander Koliopanos, Filipos Aggelakis, Konstantinos Dardoufas, Niki J. Agnanti, Irini Karydas, Georgios Nasioulas.
30. Early and Specific Prediction of the Therapeutic Efficacy in Non-Small Cell Lung Cancer Patients by Nucleosomal DNA and Cytokeratin-19 Fragments: Stefan Holdenrieder, Petra Stieber, Joachim Von Pawel, Hannelore Raith, Dorothea Nagel, Knut Feldmann and Dietrich Seidel.
Part IV: Nucleic Acids in Other Diseases:.
31. Circulating Nucleic Acids and Diabetic Complications: Asif Butt, Zaid Shalchi, Karim Hamaouri, Andjeny Samadhan, Jake Powrie, Shirley Smith, Sarah Janikoun and R. Swaminathan.
32. Circulating Nucleic Acids and Critical Illness: Timothy H. Rainer and Nicole Y. L. Lam.
33. Plasma ?-Globin DNA As a Prognostic Marker in Chest Pain Patients: Timothy H. Rainer, Nicole Y. L. Lam, C. Y. Man, Rossa W. K. Chiu, S. Woo and Y. M. Dennis Lo.
34. Cell Free DNA Levels As a Prognostic Marker in Acute Myocardial Infarction: Dionisios Antonatos, Sotirios Patsilinakos, Stavros Spanodimos, Panagiotis Korkonikitas and D. Tsigas.
Part V: Methodology:.
35. MALDI-TOP Mass Spectrometry for Quantitative, Specific and Sensitive Analysis of DNA and RNA: Chunming Ding and Y. M. Dennis Lo.
36. Rapid Prenatal Diagnosis of QF-PCR. Evaluation of 30,000 Consecutive Clinical Samples and Future Applications: Vincenzo Cirigliano, Gianfranco Voglino, Antonella Marongiu, Paz Canadas, Elena Ordonez, Elisabet Lloveras,Alberto Plaja, Carme Fuster and.
37. Higher Amount of Free Circulating DNA in Serum Than in Plasma Is Not Mainly Caused by Contaminated Extraneous DNA During Separation: Naoyuki Umetani, Susanne Hiramatsu and Dave S. B. Hoon.
38. Improvement of Methods for the Isolation of Cell-Free Fetal DNA From Maternal Plasma: Comparison of a Manual and an Automated Method: Dorothy J. Huang, Bernhard G. Zimmermann, Wolfgang Holzgreve and Sinuhe Hahn.
39. The Importance of Careful Blood Processing in Isolation of Cell Free DNA: Karen Page, Tom Powles, Martin J. Slade, Manuela Tamburo De Bella, Rosemary A. Walker, R. Charles Coombes and Jacqueline A. Shaw.
40. Nucleosomal DNA Fragments in Autoimmune Diseases: Stefan Holdenrieder, Peter Eichhorn, Ulrich Beuers, Walter Samtleben, Ulf Schoenermarck, Reinhart Zachoval, Dorothea Nagel and Petra Stieber.
41. Concentrations of Circulating RNA From Healthy Donors and Cancer Patients Estimated by Different Methods: Elena Yu Rykova, Winfried Wunsche, Olga E. Brizgunova, Tatyana E. Skvortsova, Svetlana N. Tamkovich, Ilija S. Senin, Pavel P. Laktionov, Georg Sczakiel and Valentin V. Vlassov.
42. Isolation and Comparative Study of Cell-Free Nucleic Acids From Human Urine: Olga E. Bryzgunova, Tatyana E. Skvortsova, Elena V. Kolesnikova, Audrey V. Starikov, Elena Yu Rykova, Valentin V. Vlassov and Pavel P. Laktionov.
43. Mycoplasma Infection and Extracellular RNA. Influence of Mycoplasma Contamination On the Concentration and Composition of Extracellular RNA: Evgeniy S. Morozkin, Elena Yu Rykova, Valentin V. Vlassov and Pavel P. Laktionov.
44. Optimized Real-Time Quantitative PCR Measurement of Male Fetal DNA in Maternal Plasma: Bernhard G. Zimmermann, Wolfgang Holzgreve, Neil Avent, Sinuhe Hahn.
Index of Contributors