[ RadSafe ] Chris Busby - troll? NO!

Dan W McCarn hotgreenchile at gmail.com
Mon Apr 25 18:25:03 CDT 2011

Hi Mike -

One of the most interesting papers that I have read (now several years old)
was a reporting of research from M.D. Anderson & Duke University focused on
the study of radiation effects on glioblastoma, a form of brain cancer that
is radioresistant. 

Shideng Bao1, Qiulian Wu1, Roger E. McLendon, Yueling Hao1, Qing Shi1, Anita
B. Hjelmeland, Mark W. Dewhirst, Darell D. Bigner & Jeremy N. Rich, 2006,
Glioma stem cells promote radioresistance by preferential activation of the
DNA damage response, doi:10.1038/nature05236, Published online 18 October

Ionizing radiation represents the most effective therapy for glioblastoma
(World Health Organization grade IV glioma), one of the most lethal human
malignancies1, 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.

End Quote

Chk1 and Chk2 checkpoint kinases were used in clinical trials in
glioblastoma patients demonstrating the presence of CD133 to reduce
radioresistance by blocking DNA checkpoint response.  These clinical trials
happened to include my old officemate at Shell Oil, Uncle Bernie Goldberg,
who died at the age of 86. 

The fact that this mechanism is important for glioblastoma suggests to me
that radioresistance is a normal part of the makeup of DNA, and likely has
been since early in Earth's history when background radiation levels were
significantly higher.

Dan ii

Dan W McCarn, Geologist
108 Sherwood Blvd
Los Alamos, NM 87544-3425
+1-505-672-2014 (Home – New Mexico)
+1-505-670-8123 (Mobile - New Mexico)
HotGreenChile at gmail.com (Private email) HotGreenChile at gmail dot com

-----Original Message-----
From: radsafe-bounces at health.phys.iit.edu
[mailto:radsafe-bounces at health.phys.iit.edu] On Behalf Of Stabin, Michael
Sent: Monday, April 25, 2011 11:35
To: radsafe at agni.phys.iit.edu
Subject: Re: [ RadSafe ] Chris Busby - troll? NO!

I agree with Franz really that this was not a completely accurate term to
use. It is not like the idiots (mostly bored adolescent boys I think) who
pop up on serious lists and chat rooms cursing and saying idiotic things
just to annoy people. I was being a bit provocative in the use of this term.
I am with Jerry Cohen on this, after the comment about "millions of people
dying" from low level radiation exposures and "how can you all live with
yourselves?", I saw that this is not a serious discussion and I'm not going
to pay any further attention to it or to him. Those of you who wish to
continue engaging this "stuff" (another polite term), feel free. Even if I
were still the list moderator, I would see no reason to stop debate like
this, it has seemed mostly civil to me. But it is quite a pointless waste of
time, methinks.


Michael G. Stabin, PhD, CHP
Associate Professor of Radiology and Radiological Sciences
Department of Radiology and Radiological Sciences
Vanderbilt University
1161 21st Avenue South
Nashville, TN 37232-2675
Phone (615) 343-4628
Fax   (615) 322-3764
e-mail     michael.g.stabin at vanderbilt.edu
internet   www.doseinfo-radar.com

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