Skip to main content

Proteomic Investigations for Boron Neutron Capture Therapy

  • Chapter
  • First Online:
Neutron Capture Therapy

Abstract

Proteomic investigations are of primary importance for discovery-driven biomarker studies. In fact, for understanding the biochemical and physiological differences between tumor and normal cells/tissues, and for using these differences in compound design, synthesis, and targeting, it is important to investigate protein profiles related to physiological and pathological conditions, and to describe the effect of bioactive compounds. Today, different proteomic methodologies are available for clinical proteomic applications. In this chapter, the main steps of traditional two-dimensional gel electrophoresis (2DE) and innovative multidimensional protein identification (MudPIT) are described, which are useful for BNCT investigations. In particular, some results concerning the possibility of characterizing proteins interacting with 10boron compounds and shotgun proteomic analysis of tumor tissues for biomarker discovery using a mass spectrometry-based approach are described.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Abbreviations

BSH:

Sodium mercaptoundecahydro-closo-dodecaborate

BPA:

L-para-boronophenylalanine

PVDF:

Polyvinylidene fluoride transfer membranes

MudPIT:

Multidimensional protein identification technology

LC-MS/MS:

Liquid tandem mass spectrometry

IPG:

Immobilized pH gradient

SDS-PAGE:

Sodium dodecyl sulfate-polyacrylamide gel electrophoresis

References

  1. Wilkins MR, Pasquali C, Appel RD, Ou K, Golaz O, Sanchez JC, Yan JX, Gooley AA, Hughes G, Humphrey-Smith I (1996) From proteins to proteomes – large-scale protein identification by 2-dimensional electrophoresis and amino acid analysis. Biotechnology 14:61–65

    Article  PubMed  CAS  Google Scholar 

  2. Wasinger VC, Cordwell SJ, Cerpa-Poljak A, Yan JX, Gooley AA, Wilkins MR, Duncan MW, Harris R, Williams KL, Humphery-Smith I (1995) Progress with gene-product mapping of the Mollicutes: mycoplasma genitalium. Electrophoresis 7:1090–1094

    Article  Google Scholar 

  3. Mauri PL, Petretto A, Cuccabita D, Basilico F, Di Silvestre D, Levreri I, Melioli G (2008) Fractionation techniques improve the proteomic analysis of human serum. Curr Pharm Anal 4:69–77

    Article  CAS  Google Scholar 

  4. Kaiser T, Kamal H, Rank A, Kolb HJ, Holler E, Ganser A, Hertenstein B, Mischak H, Weissinger EM (2004) Proteomics applied to the clinical follow-up of patients after allogeneic hematopoietic stem cell transplantation. Blood 104:340–349

    Article  PubMed  CAS  Google Scholar 

  5. Li J, Zhang Z, Rosenzweig J, Wang YY, Chan DW (2002) Proteomics and bioinformatics approaches for identification of serum biomarkers to detect breast cancer. Clin Chem 48:1296–1304

    PubMed  CAS  Google Scholar 

  6. Florens L, Washburn MP (2006) Proteomic analysis by multidimensional protein identification technology. Methods Mol Biol 328:159–175

    PubMed  CAS  Google Scholar 

  7. Sorio C, Mauri PL, Pederzoli P, Scarpa A (2006) Non-invasive cancer detection: strategies for the identification of novel cancer markers. IUBMB Life 58(4):193–198

    Article  PubMed  CAS  Google Scholar 

  8. Anderson NL, Anderson NG (2002) The human plasma proteome – history, character, and diagnostic prospects. Mol Cell Proteomics 1(11):845–867

    Article  PubMed  CAS  Google Scholar 

  9. Wolters DA, Washburn MP, Yates JR 3rd (2001) An automated multidimensional protein identification technology for shotgun proteomics. Anal Chem 73:5683–5690

    Article  PubMed  CAS  Google Scholar 

  10. Washburn MP, Wolters D, Yates JR 3rd (2001) Large-scale analysis of the yeast proteome by multidimensional protein identification technology. Nat Biotechnol 19:242–247

    Article  PubMed  CAS  Google Scholar 

  11. Wu CC, Yates JR 3rd (2003) The application of mass spectrometry to membrane proteomics. Nat Biotechnol 21:262–267

    Article  PubMed  CAS  Google Scholar 

  12. Lim H, Eng J, Yates JR 3rd, Tollaksen SL, Giometti CS, Holden JF, Adams MW, Reich CI, Olsen GJ, Hays LG (2003) Identification of 2D-gel proteins: a comparison of MALDI/TOF peptide mass mapping to mu LC-ESI tandem mass spectrometry. J Am Soc Mass Spectrom 14(9):957–970

    Article  PubMed  CAS  Google Scholar 

  13. Liu H, Sadygov RG, Yates JR 3rd (2004) A model for random sampling and estimation of relative protein abundance in shotgun proteomics. Anal Chem 76:4193–4201

    Article  PubMed  CAS  Google Scholar 

  14. Mauri PL, Dehò G (2008) A proteomic approach to the analysis of RNA degradosome composition in Escherichia coli. Methods Enzymol 447:99–117

    Article  PubMed  CAS  Google Scholar 

  15. Tyers M, Mann M (2003) From genomics to proteomics. Nature 422(6928):193–197

    Article  PubMed  CAS  Google Scholar 

  16. Maurya P, Meleady P, Dowling P, Clynes M (2007) Proteomic approaches for serum biomarker discovery in cancer. Anticancer Res 27(3A):1247–1255

    PubMed  CAS  Google Scholar 

  17. Mauri P, Scarpa A, Nascimbeni AC, Benazzi L, Parmagnani E, Mafficini A, Della Peruta M, Bassi C, Miyazaki K, Sorio C (2005) Identification of proteins released by pancreatic cancer cells by multidimensional protein identification technology: a strategy for identification of novel cancer markers. FASEB J 19(9):1125–1127

    PubMed  CAS  Google Scholar 

  18. Chen R, Yi EC, Donohoe S, Pan S, Eng J, Cooke K, Crispin DA, Lane Z, Goodlett DR, Bronner MP, Aebersold R, Brentnall TA (2005) Pancreatic cancer proteome: the proteins that underlie invasion, metastasis, and immunologic escape. Gastroenterology 129(4):1187–1197

    Article  PubMed  CAS  Google Scholar 

  19. Sodek KL, Evangelou AI, Ignatchenko A, Agochiya M, Brown TJ, Ringuette MJ, Jurisica I, Kislinger T (2008) Identification of pathways associated with invasive behavior by ovarian cancer cells using multidimensional protein identification technology (MudPIT). Mol Biosyst 4(7):762–773

    Article  PubMed  CAS  Google Scholar 

  20. Salinovich O, Montelaro RC (1986) Reversible staining and peptide mapping of proteins transferred to nitrocellulose after separation by sodium dodecylsulfate-polyacrylamide gel electrophoresis. Anal Biochem 156:341–347

    Article  PubMed  CAS  Google Scholar 

  21. Altieri S, Bortolussi S, Bruschi P, Chiari P, Fossati F, Stella S, Prati U, Roveda L, Zonta A, Zonta C, Ferrari C, Clerici A, Nano R, Pinelli T (2008) Neutron autoradiography imaging of selective boron uptake in human metastatic tumours. Appl Radiat Isot 66(12):1850–1855

    Article  PubMed  CAS  Google Scholar 

  22. Mauri PL, Basilico F, Wittig A, Heimans J, Sauerwein W (2006). Pharmacokinetics and metabolites of 10B-contaning compounds in biological fluids. In: Oral presentation. 12th ICNCT, Kagawa, 9 Oct 2006

    Google Scholar 

  23. Mauri PL, Basilico F, Pietta PG, Pasini E, Monti D, Sauerwein W (2003) New approach for the detection of BSH and its metabolites using capillary electrophoresis and electrospray ionization mass spectrometry. J Chromatogr B 788(1):9–16

    Article  CAS  Google Scholar 

  24. Doi A, Kawabata S, Iida K, Yokoyama K, Kajimoto Y, Kuroiwa T, Shirakawa T, Kirihata M, Kasaoka S, Maruyama K, Kumada H, Sakurai Y, Masunaga S, Ono K, Miyatake S (2008) Tumor-specific targeting of sodium borocaptate (BSH) to malignant glioma by transferrin-PEG liposomes: a modality for boron neutron capture therapy. J Neurooncol 87(3):287–294

    Article  PubMed  CAS  Google Scholar 

  25. Hale JE, Butler JP, Gelfanova V, You JS, Knierman MD (2004) A simplified procedure for the reduction and alkylation of cysteine residues in proteins prior to proteolytic digestion and mass spectral analysis. Anal Biochem 333(1):174–181

    Article  PubMed  CAS  Google Scholar 

  26. Winston RL, Fitzgerald MC (1998) Concentration and desalting of protein samples for mass spectrometry analysis. Anal Biochem 262(1):83–85

    Article  PubMed  CAS  Google Scholar 

  27. Regonesi ME, Del Favero M, Basilico F, Briani F, Benazzi L, Tortora P, Mauri P, Dehò G (2006) Analysis of the Escherichia coli RNA degradosome composition by a proteomic approach. Biochimie 88(2):151–161

    Article  PubMed  CAS  Google Scholar 

  28. Link AJ, Eng J, Schieltz DM, Carmack E, Mize GJ, Morris DR, Garvik BM, Yates JR 3rd (1999) Direct analysis of protein complexes using mass spectrometry. Nat Biotechnol 17(7):676–682

    Article  PubMed  CAS  Google Scholar 

  29. Righetti PG, Boschetti E (2007) Sherlock Holmes and the proteome – a detective story. FEBS J 274(4):897–905

    Article  PubMed  CAS  Google Scholar 

  30. Wulfkuhle JD, Paweletz CP, Steeg PS, Petricoin EF 3rd, Liotta L (2003) Proteomic approaches to the diagnosis, treatment, and monitoring of cancer. Adv Exp Med Biol 532:59–68

    Article  PubMed  CAS  Google Scholar 

  31. Ahram M, Flaig MJ, Gillespie JW, Duray PH, Linehan WM, Ornstein DK, Niu S, Zhao Y, Petricoin EF 3rd, Emmert-Buck MR (2003) Evaluation of ethanol-fixed, paraffin-embedded tissues for proteomic applications. Proteomics 3(4):413–421

    Article  PubMed  CAS  Google Scholar 

  32. Veenstra TD, Conrads TP, Hood BL, Avellino AM, Ellenbogen RG, Morrison RS (2005) Biomarkers: mining the biofluid proteome. Mol Cell Proteomics 4(4):409–418

    Article  PubMed  CAS  Google Scholar 

  33. Liu W, Brock A, Chen S, Chen S, Schultz PG (2007) Genetic incorporation of unnatural amino acids into proteins in mammalian cells. Nat Methods 4(3):239–244

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgements

The authors are grateful to Dr. A. Roveri and Dr. S. Altieri for the PHGPx reaction with BSH and neutron autoradiography, respectively.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Pier Luigi Mauri .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2012 Springer-Verlag Berlin Heidelberg

About this chapter

Cite this chapter

Mauri, P.L., Basilico, F. (2012). Proteomic Investigations for Boron Neutron Capture Therapy. In: Sauerwein, W., Wittig, A., Moss, R., Nakagawa, Y. (eds) Neutron Capture Therapy. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-31334-9_10

Download citation

  • DOI: https://doi.org/10.1007/978-3-642-31334-9_10

  • Published:

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-642-31333-2

  • Online ISBN: 978-3-642-31334-9

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics