H&N cancer patient, make sure your vitamin D status is ok before radiotherapy & chemo
- From: Matti Narkia <mna@xxxxxxxx>
- Date: Thu, 19 Apr 2007 01:45:43 +0300
The following abstract from 2007 AACR meeting suggests that the active
form of vitamin D may decrease the ability of head and neck cancer
cells to survive radiation or chemotherapy by impairing the DNA damage
response ultimately leading to apoptosis:
Abstract Number: LB-295
Presentation Title: Vitamin D-mediated inhibition of Rad51
expression in head and neck squamous cell
carcinoma.
Presentation Start/End Time: Tuesday, Apr 17, 2007, 1:00 PM - 5:00 PM
Location: Exhibit Hall, Los Angeles Convention
Center
Author Block: Joanna S. Albala, Christopher A. Bradley,
Shey-Jen Shih, Andrew T. Vaughan, Danny
J. Enepekides, Gregory Farwell. UC Davis
School of Medicine, Sacramento, CA
Numerous studies have demonstrated the pro-apoptotic and
anti-proliferative effects of the active form of vitamin D, vitamin D3
(VD3), in a variety of cancers, including head and neck squamous cell
carcinoma. The molecular mechanisms through which VD3 mediates these
effects remain unknown. Rad51 is a key protein involved in the repair
of DNA double-strand breaks induced by ionizing radiation and
overexpression of Rad51 has been shown to increase cellular resistance
to radiation and chemotherapy in several cancer types. High levels of
endogenous Rad51 protein in head and neck squamous cell carcinoma have
been correlated to poor prognosis and resistance to treatment.
Preliminary work in our lab has shown that VD3 down-regulates Rad51
protein expression in squamous cell carcinoma in vitro. Furthermore,
VD3 antagonized radiation-induced induction of Rad51. Pretreatment of
SCC25 cells with VD3 twenty-four hours prior to irradiation reduced
the formation of H2AX foci and decreased sublethal DNA damage repair.
Functional analysis of Rad51 by foci formation after treatment with
VD3 and IR is currently under investigation. Combined treatment of VD3
and radiation showed an increase in caspase-3 cleavage, a measure of
increased apoptosis. This suggests that application of VD3 may
decrease the ability of head and neck cancer cells to survive
radiation or chemotherapy by impairing the DNA damage response
ultimately leading to apoptosis. This has obvious therapeutic
implications as vitamin D-mediated inhibition of Rad51 expression
could modulate the response of head and neck cancers to treatment.
--
Matti Narkia
.
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