Skip to main content
Article thumbnail
Location of Repository

Nucleosomes in pancreatic cancer patients during radiochemotherapy

By Andreas Kremer, Ralf Wilkowski, Stefan Holdenrieder, Dorothea Nagel, Petra Stieber and Dietrich Seidel

Abstract

Nucleosomes appear spontaneously in elevated concentrations in the serum of patients with malignant diseases as well as during chemo- and radiotherapy. We analyzed whether their kinetics show typical characteristics during radiochemotherapy and enable an early estimation of therapy efficacy. We used the Cell Death Detection Elisaplus ( Roche Diagnostics) and investigated the course of nucleosomes in the serum of 32 patients with a local stage of pancreatic cancer who were treated with radiochemotherapy for several weeks. Ten of them received postsurgical therapy, 21 received primary therapy and 1 received therapy for local relapse. Blood was taken before the beginning of therapy, daily during the first week, once weekly during the following weeks and at the end of radiochemotherapy. The response to therapy was defined according to the kinetics of CA 19-9: a decrease of CA 19-9 650% after radiochemotherapy was considered as `remission'; an increase of >= 100% ( which was confirmed by two following values) was defined as `progression'. Patients with `stable disease' ranged intermediately. Most of the examined patients showed a decrease of the concentration of nucleosomes within 6 h after the first dose of radiation. Afterwards, nucleosome levels increased rapidly, reaching their maximum during the following days. Patients receiving postsurgery, primary or relapse therapies did not show significant differences in nucleosome values during the time of treatment. Single nucleosome values, measured at 6, 24 and 48 h after the application of therapy, could not discriminate significantly between patients with no progression and those with progression of disease. However, the area under the curve of the first 3 days, which integrated all variables of the initial therapeutic phase, showed a significant correlation with the progression-free interval ( p = 0.008). Our results indicate that the area under the curve of nucleosomes during the initial phase of radiochemotherapy could be valuable for the early prediction of the progression-free interval. Copyright (C) 2005 S. Karger AG, Basel.

Topics: Medizin, ddc:610
Publisher: Ludwig-Maximilians-Universität München
Year: 2005
DOI identifier: 10.1159/000084339
OAI identifier: oai:epub.ub.uni-muenchen.de:16325
Provided by: Open Access LMU

Suggested articles

Citations

  1. (1999). A: CA 19-9: A predictor of response in pancreatic cancer treated with gemcitabine and cisplatin. Anticancer Res
  2. (2003). Aarden LA: Time between onset of apoptosis and release of nucleosomes from apoptotic cells: Putative implications for systemic lupus erythematosus. Ann Rheum Dis
  3. AH: Apoptosis. The role of the endonuclease.
  4. (2003). Are serial CA 19-9 kinetics helpful predicting survival in patients with advanced or metastatic pancreatic cancer treated with gemcitabine and cisplatin? Onkologie
  5. (1996). Blood clearance kinetics and liver uptake of mononucleosomes in mice.
  6. (1994). BV: Apoptosis. Its significance in cancer and cancer therapy.
  7. C: The use of DNA double-strand break quantification in radiotherapy.
  8. Circulating nucleosomes in serum.
  9. Clinical significance of plasma nucleosome levels in cancer patients.
  10. (1997). CM: Apoptosis and mitotic cell death: Their relative contributions to normal-tissue and tumour radiation response.
  11. Cocks RA: Plasma DNA as a prognostic marker in trauma patients.
  12. CR: Hemodialysis as a model for studying endogenous plasma DNA: Oligonucleosomelike structure and clearance. Clin Exp Immunol
  13. (1999). Doubling time of serum CA 19-9 in the clinical course of patients with pancreatic cancer and its significant association with prognosis.
  14. (2001). Genomic instability: Potential contributions to tumour and normal tissue response, and second tumours, after radiotherapy. Radiother Oncol
  15. (1998). Hjelm NM: Presence of donor-specific DNA in plasma of kidney and liver-transplant recipients. Lancet
  16. Increased apoptosis is specific for acute rejection in rat small bowel transplant.
  17. (1997). Koutouzov S: Circulating plasma levels of nucleosomes in patients with systemic lupus erythematosus: Correlation with serum antinucleosome antibody titers and absence of clear association with disease activity. Arthritis Rheum
  18. (1994). L: Radiation-induced apoptosis in a murine lymphoma in vivo. Radiother Oncol
  19. (2003). Lo YM: Prognostic use of circulating plasma nucleic acid concentrations in patients with acute stroke. Clin Chem
  20. Locally advanced pancreatic carcinoma. Radiochemotherapy prolongs survival.
  21. (1998). Monitoring and signaling of radiation-induced damage in mammalian cells. Radiat Res
  22. Müller MM: Increased concentrations of cell-free plasma DNA after exhaustive exercise.
  23. Nucleosomes in serum of patients with benign and malignant diseases.
  24. (2004). Nucleosomes indicate the in vitro radiosensitivity of irradiated broncho-epithelial and lung cancer cells. Tumor Biol
  25. (1993). Peters LJ: Heterogeneity in the development of apoptosis in irradiated murine tumours of different histologies.
  26. Present and future treatment of pancreatic cancer.
  27. (1996). RA: Accelerated repopulation during fractionated irradiation of a murine ovarian carcinoma: Downregulation of apoptosis as a possible mechanism.
  28. (1998). S: A caspase-activated DNase that degrades DNA during apoptosis, and its inhibitor ICAD.
  29. (1997). S: CA 19-9 in evaluating the response to chemotherapy in advanced pancreatic cancer. Hepatogastroenterology
  30. (1999). Seidel D: Apoptosis in serum of patients with solid tumours. Anticancer Res
  31. (2001). Seidel D: Nucleosomes in serum as a marker for cell death. Clin Chem Lab Med
  32. Spontaneous DNA damage, genome instability, and cancer – When DNA replication escapes control.
  33. (2002). Stahel RA: Circulating DNA: A new diagnostic gold mine? Cancer Treat Rev
  34. Structure and dynamic behavior of nucleosomes.
  35. T: Apoptosis induced by low-dose and low-dose-rate radiation. Cancer 2002;94:
  36. (1992). The apoptosis endonuclease and its regulation. Semin Immunol
  37. (1999). The cellular response to p53: The decision between life and death. Oncogene
  38. (1997). The shape of cell death.
  39. (1999). Twenty-five years of the nucleosome, fundamental particle of the eukaryote chromosome.
  40. U: Predictive value of carbohydrate antigen 19-9 in pancreatic cancer treated with radiochemotherapy.

To submit an update or takedown request for this paper, please submit an Update/Correction/Removal Request.