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Radiation-hypersensitive cancer patients do not manifest protein expression abnormalities in components of the nonhomologous end-joining (NHEJ) pathway.

Leong T, Chao M, Bassal S, McKay M - Br. J. Cancer (2003)

Bottom Line: In this study, we took a biochemical approach to evaluate the potential role of key ionising radiation repair proteins in the treatment outcomes of patients with severe acute or late RT side effects.We did not observe any abnormalities in expression level or migration pattern of the following NHEJ proteins in radiosensitive cancer cases: Ku70, Ku80, XRCC4, DNA Ligase IV.These important negative results provide evidence that mutations that affect protein expression of these NHEJ components are unlikely to underlie clinical radiation sensitivity.

View Article: PubMed Central - PubMed

Affiliation: Peter MacCallum Cancer Center Institute, St Andrews Place, East Melbourne, Victoria, Australia.

ABSTRACT
Radiation therapy (RT) is utilised for the treatment of around half of all oncology patients during the course of their illness. Despite great clinical progress in the rational deployment of RT, the underlying molecular basis for its efficacy and toxicity are currently imperfectly understood. In this study, we took a biochemical approach to evaluate the potential role of key ionising radiation repair proteins in the treatment outcomes of patients with severe acute or late RT side effects. Lymphoblastoid cell lines were established from blood samples from 36 radiosensitive cases and a number of controls (the latter had had RT but did not develop significant toxicity). The expression level and migration of key proteins from the nonhomologous end-joining (NHEJ) pathway was evaluated by Western blot analysis on cases and controls. We did not observe any abnormalities in expression level or migration pattern of the following NHEJ proteins in radiosensitive cancer cases: Ku70, Ku80, XRCC4, DNA Ligase IV. These important negative results provide evidence that mutations that affect protein expression of these NHEJ components are unlikely to underlie clinical radiation sensitivity.

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Photograph showing an example of a severe late radiation reaction. This patient (patient 8 in Table 1 Table 1Patient characteristics
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fig1: Photograph showing an example of a severe late radiation reaction. This patient (patient 8 in Table 1 Table 1Patient characteristics

Mentions: The patient cohort for this study comprised 36 radiation-sensitive individuals referred by radiation oncologists at Peter MacCallum Cancer Institute and several other centres within Australia. A highly radiosensitive response was defined as a clinically overt and unexpectedly severe radiation reaction (RTOG grades 3 and 4) which occurred either acutely (during or within weeks of completion of RT) or as a late adverse reaction (months to years after completion of the RT course) (Figure 1Figure 1


Radiation-hypersensitive cancer patients do not manifest protein expression abnormalities in components of the nonhomologous end-joining (NHEJ) pathway.

Leong T, Chao M, Bassal S, McKay M - Br. J. Cancer (2003)

Photograph showing an example of a severe late radiation reaction. This patient (patient 8 in Table 1 Table 1Patient characteristics
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2747564&req=5

fig1: Photograph showing an example of a severe late radiation reaction. This patient (patient 8 in Table 1 Table 1Patient characteristics
Mentions: The patient cohort for this study comprised 36 radiation-sensitive individuals referred by radiation oncologists at Peter MacCallum Cancer Institute and several other centres within Australia. A highly radiosensitive response was defined as a clinically overt and unexpectedly severe radiation reaction (RTOG grades 3 and 4) which occurred either acutely (during or within weeks of completion of RT) or as a late adverse reaction (months to years after completion of the RT course) (Figure 1Figure 1

Bottom Line: In this study, we took a biochemical approach to evaluate the potential role of key ionising radiation repair proteins in the treatment outcomes of patients with severe acute or late RT side effects.We did not observe any abnormalities in expression level or migration pattern of the following NHEJ proteins in radiosensitive cancer cases: Ku70, Ku80, XRCC4, DNA Ligase IV.These important negative results provide evidence that mutations that affect protein expression of these NHEJ components are unlikely to underlie clinical radiation sensitivity.

View Article: PubMed Central - PubMed

Affiliation: Peter MacCallum Cancer Center Institute, St Andrews Place, East Melbourne, Victoria, Australia.

ABSTRACT
Radiation therapy (RT) is utilised for the treatment of around half of all oncology patients during the course of their illness. Despite great clinical progress in the rational deployment of RT, the underlying molecular basis for its efficacy and toxicity are currently imperfectly understood. In this study, we took a biochemical approach to evaluate the potential role of key ionising radiation repair proteins in the treatment outcomes of patients with severe acute or late RT side effects. Lymphoblastoid cell lines were established from blood samples from 36 radiosensitive cases and a number of controls (the latter had had RT but did not develop significant toxicity). The expression level and migration of key proteins from the nonhomologous end-joining (NHEJ) pathway was evaluated by Western blot analysis on cases and controls. We did not observe any abnormalities in expression level or migration pattern of the following NHEJ proteins in radiosensitive cancer cases: Ku70, Ku80, XRCC4, DNA Ligase IV. These important negative results provide evidence that mutations that affect protein expression of these NHEJ components are unlikely to underlie clinical radiation sensitivity.

Show MeSH
Related in: MedlinePlus