[ RadSafe ] Radiation for health

[Dan W McCarn]

Hi Bjorn:

For me, this subject is a strictly from the viewpoint of "spectator sport",
but I can't help but reflect on the letter in Nature on October 18, 2006
about Glioma stem cell radio-resistance.

Duke University and MD Anderson are in the process of a clinical trial
utilizing one of the mechanisms of radiation resistance in Glioblastoma
patients.  They found that a lipoprotein present in some of the Glioma stem
cells seemed to control radiation resistance.

The researchers developed a vaccine and were able to suppress some of the
radiation resistance.  I'm not sure if they blocked the CD-133 protein or
the DNA damage checkpoint.  My roommate at Shell Oil benefited from this
research when he was diagnosed in late October 2006 with Glioblastoma which
expressed the CD-133 characteristic.  I just happened to read the paper the
week before he fell ill.  He became part of their clinical trials.

Below is the abstract and exact reference for you!

What is fascinating is that cancer researchers are exploring one of the
bases of radiation resistance through a very practical understanding of the
mechanisms. Perhaps someday, a vaccine might be developed that will allow
the CD-133 lipoprotein (and perhaps others) to be expressed continuously
throughout the body and "vaccinate" one to some degree against cancer.

Clearly, they base their research on the observed expression of the CD-133
lipoprotein from XRAY & gamma radiation and the control of the DNA damage
checkpoint.

Bjorn, I also built a Van de Graff type linear accelerator when I was a kid
back 40 or so years ago and irradiated seeds.  My "coach" only allowed me to
use an aluminum target.

Dan ii

Dan W McCarn, Geologist
Albuquerque & Houston
-------------------------------------------------------------------------
doi:10.1038/nature05236

Glioma stem cells promote radioresistance by preferential activation of the
DNA damage response; Shideng Bao 1,2, Qiulian Wu1, 2, Roger E. McLendon 2,3,
Yueling Hao 1,2, Qing Shi1, 2, Anita B. Hjelmeland1, 2, Mark W. Dewhirst 4,
Darell D. Bigner 2,3 & Jeremy N. Rich 1,2,5,6

Ionizing radiation represents the most effective therapy for glioblastoma
(World Health Organization grade IV glioma), one of the most lethal human
malignancies, but radiotherapy remains only palliative2 because of
radioresistance. The mechanisms underlying tumour radioresistance have
remained elusive. Here we show that cancer stem cells contribute to glioma
radioresistance through preferential activation of the DNA damage checkpoint
response and an increase in DNA repair capacity. The fraction of tumour
cells expressing CD133 (Prominin-1), a marker for both neural stem cells and
brain cancer stem cells3-6, is enriched after radiation in gliomas. In both
cell culture and the brains of immunocompromised mice, CD133-expressing
glioma cells survive ionizing radiation in increased proportions relative to
most tumour cells, which lack CD133. CD133-expressing tumour cells isolated
from both human glioma xenografts and primary patient glioblastoma specimens
preferentially activate the DNA damage checkpoint in response to radiation,
and repair radiation-induced DNA damage more effectively than CD133-negative
tumour cells. In addition, the radioresistance of CD133-positive glioma stem
cells can be reversed with a specific inhibitor of the Chk1 and Chk2
checkpoint kinases. Our results suggest that CD133-positive tumour cells
represent the cellular population that confers glioma radioresistance and
could be the source of tumour recurrence after radiation. Targeting DNA
damage checkpoint response in cancer stem cells may overcome this
radioresistance and provide a therapeutic model for malignant brain cancers.

1 Department of Surgery, 2 Preston Robert Tisch Brain Tumor Center,
Department of Pathology, 4 Department of Radiation Oncology, 5 Department of
Medicine, and 6 Department of Neurobiology, Duke University Medical Center,
Durham, North Carolina 27710, USA.

-----Original Message-----
From: radsafe-bounces at radlab.nl [mailto:radsafe-bounces at radlab.nl] On Behalf
Of Bjorn Cedervall
Sent: Thursday, June 19, 2008 11:43 AM
To: radsafe at radlab.nl
Subject: RE: [ RadSafe ] Radiation for health


> Does anyone actually believe in LNT? It certainly makes it easy to produce
> an effect regulatory frame work, but I do not think it is true.
LNT is an administrative tool - the actual shape in the lower dose region
(say less
than 10 mGy as an acute dose) will probably never be known. We can only do
"educated guesses" based on molecular and other phenomena + clinical
information
we study in various ways - their potential relevance depending on context
etc.
 
Bearing this in mind, it shouldn't be about believing. I am personally
convinced that
a single ionization may be the first step in a series of events that
ultimately may
result in an aggressive tumor. This does not make me think that the detailed
dose-response has any particular shape - and furthermore it does not make me
particularly worried about radiation. High blood pressure for instance
should
be of much larger concern for most people than getting some extra and
trivial
dose of ionizing radiation exposure (I did my first radiation experiments
(with
Co-60 and an X-ray tube) in high school more than 40 years ago.
 
My personal reflections only,
 
Bjorn Cedervall
 
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