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The association of DNA-dependent protein kinase activity of peripheral blood lymphocytes with prognosis of cancer.

Someya M, Sakata KI, Matsumoto Y, Kamdar RP, Kai M, Toyota M, Hareyama M - Br. J. Cancer (2011)

Bottom Line: DNA-PK activity of PBLs in advanced cancer patients was significantly lower than that in early stage.The DNA-PK activity of PBLs in most patients decreased in response to radiation as the equivalent whole-body dose increased.Therefore, DNA-PK activity in PBLs could be used as a marker to predict the chromosomal instability and poorer prognosis.

View Article: PubMed Central - PubMed

Affiliation: Department of Radiology, Sapporo Medical University, School of Medicine, Hokkaido, Japan.

ABSTRACT

Background: Repair of various types of DNA damages is critical for genomic stability. DNA-dependent protein kinase (DNA-PK) has an important role in DNA double-strand break repair. We examined whether there may be a correlation between DNA-PK activity in peripheral blood lymphocytes (PBLs) and survival percentages in various cancer patients. We also investigated the changes of DNA-PK activity in PBLs after radiotherapy.

Methods: A total of 167 of untreated cancer patients participated in this study. Peripheral blood was collected, separated, and centrifuged. DNA-PK activity was measured by DNA-pull-down assay. Chromosomal aberrations were examined by cytogenetic methods.

Results: DNA-PK activity of PBLs in advanced cancer patients was significantly lower than that in early stage. The patients with lower DNA-PK activity in PBLs tended to have the lower disease-specific survivals and distant metastasis-free survivals than those with higher DNA-PK activity in advanced stages. There was also a tendency of inverse correlation between DNA-PK activity and excess fragments. The DNA-PK activity of PBLs in most patients decreased in response to radiation as the equivalent whole-body dose increased.

Conclusion: Cancer patients in advanced stage, with lower DNA-PK activity of PBLs might have higher distant metastasis and exhibit poorer prognosis. Therefore, DNA-PK activity in PBLs could be used as a marker to predict the chromosomal instability and poorer prognosis.

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(A) DNA-PK activity in PBLs of patients with varied cancer types. Cancer patients were separated into two categories by stage: the early stage and the advanced stage. The horizontal bar indicates the mean value. (B) Disease-specific survival of cancer patients treated with radiotherapy according to stage and DNA-PK activity in PBLs. ‘Early high DNA-PK' included 65 patients; ‘early low DNA-PK' included 69 patients; ‘advanced high DNA-PK' included 9 patients; ‘advanced low DNA-PK' included 24 patients. (C) Distant metastasis-free survival of cancer patients treated with radiotherapy according to stage and DNA-PK activity in PBLs. (D) Correlation between chromosomal aberrations and DNA-PK activity of PBLs. The number of excess fragments in 200 mitotic metaphase cells was counted and expressed as the number per cell. Open circle, PBLs of patients with early stage; closed circle, that with advanced stage. The line is the regression curve.
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fig1: (A) DNA-PK activity in PBLs of patients with varied cancer types. Cancer patients were separated into two categories by stage: the early stage and the advanced stage. The horizontal bar indicates the mean value. (B) Disease-specific survival of cancer patients treated with radiotherapy according to stage and DNA-PK activity in PBLs. ‘Early high DNA-PK' included 65 patients; ‘early low DNA-PK' included 69 patients; ‘advanced high DNA-PK' included 9 patients; ‘advanced low DNA-PK' included 24 patients. (C) Distant metastasis-free survival of cancer patients treated with radiotherapy according to stage and DNA-PK activity in PBLs. (D) Correlation between chromosomal aberrations and DNA-PK activity of PBLs. The number of excess fragments in 200 mitotic metaphase cells was counted and expressed as the number per cell. Open circle, PBLs of patients with early stage; closed circle, that with advanced stage. The line is the regression curve.

Mentions: Figure 1A compared the DNA-PK activity in PBLs of cancer patients in early and advanced stages before treatment. It was measured as 10.0±5.5 pmol (mean±s.d.) and 7.9±3.5 pmol, respectively. DNA-PK activity was found to be significantly lower in advanced cancer than in early stage (P=0.007). We obtained a blood sample from a normal volunteer on 11 other days from December 2002 to March 2004, and measured the DNA-PK activity of PBL to examine its intra-individual variability. It was measured as 15.0±2.8 pmol, indicating that DNA-PK activity of PBL may be relatively constant.


The association of DNA-dependent protein kinase activity of peripheral blood lymphocytes with prognosis of cancer.

Someya M, Sakata KI, Matsumoto Y, Kamdar RP, Kai M, Toyota M, Hareyama M - Br. J. Cancer (2011)

(A) DNA-PK activity in PBLs of patients with varied cancer types. Cancer patients were separated into two categories by stage: the early stage and the advanced stage. The horizontal bar indicates the mean value. (B) Disease-specific survival of cancer patients treated with radiotherapy according to stage and DNA-PK activity in PBLs. ‘Early high DNA-PK' included 65 patients; ‘early low DNA-PK' included 69 patients; ‘advanced high DNA-PK' included 9 patients; ‘advanced low DNA-PK' included 24 patients. (C) Distant metastasis-free survival of cancer patients treated with radiotherapy according to stage and DNA-PK activity in PBLs. (D) Correlation between chromosomal aberrations and DNA-PK activity of PBLs. The number of excess fragments in 200 mitotic metaphase cells was counted and expressed as the number per cell. Open circle, PBLs of patients with early stage; closed circle, that with advanced stage. The line is the regression curve.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3111168&req=5

fig1: (A) DNA-PK activity in PBLs of patients with varied cancer types. Cancer patients were separated into two categories by stage: the early stage and the advanced stage. The horizontal bar indicates the mean value. (B) Disease-specific survival of cancer patients treated with radiotherapy according to stage and DNA-PK activity in PBLs. ‘Early high DNA-PK' included 65 patients; ‘early low DNA-PK' included 69 patients; ‘advanced high DNA-PK' included 9 patients; ‘advanced low DNA-PK' included 24 patients. (C) Distant metastasis-free survival of cancer patients treated with radiotherapy according to stage and DNA-PK activity in PBLs. (D) Correlation between chromosomal aberrations and DNA-PK activity of PBLs. The number of excess fragments in 200 mitotic metaphase cells was counted and expressed as the number per cell. Open circle, PBLs of patients with early stage; closed circle, that with advanced stage. The line is the regression curve.
Mentions: Figure 1A compared the DNA-PK activity in PBLs of cancer patients in early and advanced stages before treatment. It was measured as 10.0±5.5 pmol (mean±s.d.) and 7.9±3.5 pmol, respectively. DNA-PK activity was found to be significantly lower in advanced cancer than in early stage (P=0.007). We obtained a blood sample from a normal volunteer on 11 other days from December 2002 to March 2004, and measured the DNA-PK activity of PBL to examine its intra-individual variability. It was measured as 15.0±2.8 pmol, indicating that DNA-PK activity of PBL may be relatively constant.

Bottom Line: DNA-PK activity of PBLs in advanced cancer patients was significantly lower than that in early stage.The DNA-PK activity of PBLs in most patients decreased in response to radiation as the equivalent whole-body dose increased.Therefore, DNA-PK activity in PBLs could be used as a marker to predict the chromosomal instability and poorer prognosis.

View Article: PubMed Central - PubMed

Affiliation: Department of Radiology, Sapporo Medical University, School of Medicine, Hokkaido, Japan.

ABSTRACT

Background: Repair of various types of DNA damages is critical for genomic stability. DNA-dependent protein kinase (DNA-PK) has an important role in DNA double-strand break repair. We examined whether there may be a correlation between DNA-PK activity in peripheral blood lymphocytes (PBLs) and survival percentages in various cancer patients. We also investigated the changes of DNA-PK activity in PBLs after radiotherapy.

Methods: A total of 167 of untreated cancer patients participated in this study. Peripheral blood was collected, separated, and centrifuged. DNA-PK activity was measured by DNA-pull-down assay. Chromosomal aberrations were examined by cytogenetic methods.

Results: DNA-PK activity of PBLs in advanced cancer patients was significantly lower than that in early stage. The patients with lower DNA-PK activity in PBLs tended to have the lower disease-specific survivals and distant metastasis-free survivals than those with higher DNA-PK activity in advanced stages. There was also a tendency of inverse correlation between DNA-PK activity and excess fragments. The DNA-PK activity of PBLs in most patients decreased in response to radiation as the equivalent whole-body dose increased.

Conclusion: Cancer patients in advanced stage, with lower DNA-PK activity of PBLs might have higher distant metastasis and exhibit poorer prognosis. Therefore, DNA-PK activity in PBLs could be used as a marker to predict the chromosomal instability and poorer prognosis.

Show MeSH
Related in: MedlinePlus