Annals of the New York Academy of Sciences, Circulating Nucleic Acids in Plasma and Serum IV / Edition 1

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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 th

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Table of Contents

Welcoming Remarks: P. Whitfield.

Circulating Nicleic Acids in Plasma and Serum RecentDevelopments: R. Swaminathan and Asif N. Butt.

Part I: Biology of Circulating Nucleic Acids:.

1. Prehistory of CNAPS, the Birth of a Hypothesis: CirculatingDNA.: 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 AndMaurice Stroun.

4. Biology of Circulating Mrna – Still More Questions ThanAnswers: Michael Fleischhacker.

5. Investigation of the Origin of Extracellular RNA in HumanCell 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, JoeLeigh Simpson And Dorothy E. Lewis.

Part II: Fetal Nucleic Acids:.

7. Fetal Nucleic Acids in Maternal Body Fluids: an Update: DianaW. Bianchi, Tuangsit Wataganara, Olav Lapaire, May Lee Tjoa, JillL. 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, AngeloantonioVitucci, 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 FetalGene Expression Profiling: Nancy B. Y. Tsui And Y. M. DennisLo.

11. Development and Application of a Real Time Quantitative PCRfor Prenatal Detection of Fetal O-Thalassemia From MaternalPlasma.

Warunee Tungwiwat, Supan Fucharoen, Goonnapa Fucharoen,Thawalwong Ratanasiri And Kanokwan Anchaisuriya.

12. Detection of a Paternally Fetal Mutation in Maternal Plasmaby the Use of Automatic Sequencing: Ana Bustamante-Aragones, MariaGarcia-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) inPre-Eclampsia: a Link with Elevated Levels of Cell-Free DNA?:Anurag Gupta, Paul Hasler, Stephen Gebhardt, Wolfgang And SinuheHahn.

14. Use of Bi-Allelic Insertion/Deletion Polymorphisms As aPositive Control for Fetal Genotyping in Maternal Blood: FirstClinical Experience: Godelieve Cml Page-Christiaens, BernadetteBossers, C. Ellen Van Der Schoot, Masja De Haas.

15. PLAC1 Mrna in Maternal Blood Correlates with Doppler ofUterine Arteries Waveform in Normal Pregnancies At 2nd and 3rdTrimester: Antonio Farina, Manuela Concu, Irina Banzola, AnnalisaTempesta,Sonia Vagnoni, Sandro Gabrielli, Mara Mattioli, PaoloCarinci, Gianluigi Pilu, Danila Morano, Nicola Rizzo.

16. Different Approaches for Non-Invasive Prenatal Diagnosis ofGenetic Diseases Based On PNA-Mediated Enriched PCR: GalbiatiSilvia, Restagno Gabriella, Foglieni Barbara, Bonalumi Sara, TraviMaurizio, Piga Antonio, Sbaiz Luca, Chiari Marcella, DaminFrancesco Smid Maddalena, Valsecchi Luca, Pasi Federica, FerrariAnd Laura Cremonesi.

17. Detection of Snps in the Plasma of Pregnant Women and in theUrine of Kidney Transplant Recipients by Mass Spectrometry: YingLi, Deidre Hahn, Friedel Wenzel, Wolfgang Holzgreve And SinuheHahn.

18. Non-Invasive Prenatal Diagnostic Assay for the Detection of-Thalassaemia: Thessalia Papasavva, Gabriel Kalakoutis, IoannisKalikas, Lectra Noekli, Soteroula Papacharalambous, Andreanni YrriAnd Marina Kleanthous.

Part III: Nucleic Acids and Cancer:.

19. Circulating DNA and Lung Cancer: Xiaoyan Xue, Yong M. ZhuAnd Penella J. Woll.

20. Circulating Nucleic Acids in Plasma/Serum and TumourProgression: Are Apoptotic Bodies Involved? an Experimental Studyin 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 andPlasma: Yi-Ching Wang, Han-Shui Hsu, Tsz-Pei Chen And Jung-TaChen.

23. Quantitative Analysis of Plasma DNA in Colorectal CancerPatients: a Novel Prognostic Tool: Milo Frattini, GianfrancescoGallino, 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: SvetlanaN. Tamkovich, Anna V. Cherepanova, Elena Yu. Rykova, Dmitrii V.Pyshnyi, Valentin V. Vlassov And Pavel P. Laktionov.

Comparative Analysis of Mesenteric and Peripheral BloodCirculating Tumour DNA in Colorectal Cancer Patients: Bret Taback,Sukamal Saha And Dave S. B. Hoon.

25. Real Time Quantification of Human Telomerase ReverseTranscriptase 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 StageBreast 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 CirculatingMicrosatellite-DNA in Blood Plasma Samples of Patients withProstate Cancer and Benign Prostatic Hyperplasia: Imke Müller,Karoline Urban, Klaus Panel and Heidi Schwarzenbach.

28. Quantification of Total Plasma Cell-Free DNA in OvarianCancer Using Real Time PCR: Aparna A. Kamat, Anil K. Sood, DianneDang, David M. Gershenson, Joe L. Simpson and Farideh Z.Bischoff.

29. Cell-Free DNA and RNA in Plasma As a New Molecular Markerfor Prostate and Breast Cancer: Eirini Papadopoulou, Elias Davilas,Vasilios Sotiriou, Eleftherios Georgakopoulos, StravroulaGeorgakopoulou, Alexander Koliopanos, Filipos Aggelakis,Konstantinos Dardoufas, Niki J. Agnanti, Irini Karydas, GeorgiosNasioulas.

30. Early and Specific Prediction of the Therapeutic Efficacy inNon-Small Cell Lung Cancer Patients by Nucleosomal DNA andCytokeratin-19 Fragments: Stefan Holdenrieder, Petra Stieber,Joachim Von Pawel, Hannelore Raith, Dorothea Nagel, Knut Feldmannand Dietrich Seidel.

Part IV: Nucleic Acids in Other Diseases:.

31. Circulating Nucleic Acids and Diabetic Complications: AsifButt, 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 β-Globin DNA As a Prognostic Marker in Chest PainPatients: 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 AcuteMyocardial Infarction: Dionisios Antonatos, Sotirios Patsilinakos,Stavros Spanodimos, Panagiotis Korkonikitas and D. Tsigas.

Part V: Methodology:.

35. MALDI-TOP Mass Spectrometry for Quantitative, Specific andSensitive Analysis of DNA and RNA: Chunming Ding and Y. M. DennisLo.

36. Rapid Prenatal Diagnosis of QF-PCR. Evaluation of 30,000Consecutive Clinical Samples and Future Applications: VincenzoCirigliano, Gianfranco Voglino, Antonella Marongiu, Paz Canadas,Elena Ordonez, Elisabet Lloveras,Alberto Plaja, Carme Fusterand.

Matteo Adinolfi.

37. Higher Amount of Free Circulating DNA in Serum Than inPlasma Is Not Mainly Caused by Contaminated Extraneous DNA DuringSeparation: Naoyuki Umetani, Susanne Hiramatsu and Dave S. B.Hoon.

38. Improvement of Methods for the Isolation of Cell-Free FetalDNA From Maternal Plasma: Comparison of a Manual and an AutomatedMethod: Dorothy J. Huang, Bernhard G. Zimmermann, WolfgangHolzgreve and Sinuhe Hahn.

39. The Importance of Careful Blood Processing in Isolation ofCell Free DNA: Karen Page, Tom Powles, Martin J. Slade, ManuelaTamburo De Bella, Rosemary A. Walker, R. Charles Coombes andJacqueline A. Shaw.

40. Nucleosomal DNA Fragments in Autoimmune Diseases: StefanHoldenrieder, Peter Eichhorn, Ulrich Beuers, Walter Samtleben, UlfSchoenermarck, Reinhart Zachoval, Dorothea Nagel and PetraStieber.

41. Concentrations of Circulating RNA From Healthy Donors andCancer 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, GeorgSczakiel and Valentin V. Vlassov.

42. Isolation and Comparative Study of Cell-Free Nucleic AcidsFrom Human Urine: Olga E. Bryzgunova, Tatyana E. Skvortsova, ElenaV. Kolesnikova, Audrey V. Starikov, Elena Yu Rykova, Valentin V.Vlassov and Pavel P. Laktionov.

43. Mycoplasma Infection and Extracellular RNA. Influence ofMycoplasma Contamination On the Concentration and Composition ofExtracellular RNA: Evgeniy S. Morozkin, Elena Yu Rykova, ValentinV. Vlassov and Pavel P. Laktionov.

44. Optimized Real-Time Quantitative PCR Measurement of MaleFetal DNA in Maternal Plasma: Bernhard G. Zimmermann, WolfgangHolzgreve, Neil Avent, Sinuhe Hahn.

Index of Contributors

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