Re: Cancer treatment question/Hyperthermia

["Björn Cedervall" <bjorn_cedervall@hotmail.com>]

The cell death due to hyperthermia seems mainly to be due
to effects on S-phase cells (which normally are most resistant
to ionizing radiation). In an experiment with CHO cells where
we investigated the effects of combined X-rays and heat and
studied the bulk DNA (by fluorescence) and S-phase DNA (by
labelling) independently with had a very low effect on bulk
DNA whereas 10 min. at 45.5 degrees C was equivalent to 200 Gy
(if I remember correctly) in terms of DSBs. Most probably
protein structures fall abart due to the hyperthermia (ref.
Wong R.S.L., Dynlacht J., Cedervall B., and Dewey W.C., Analysis of DNA 
double-strand breaks by pulsed field gel electrophoresis of heated and/or 
X-irradiated Chinese hamster ovary cells. International Journal of Radiation 
Biology Vol. 68, 1995:141-152.).

Another theoretical advantage with heat is that the tumor
microvolumes that are hypoxic (and therefore difficult to kill
with ionizing radiation) usually have a low supply of well
functioning bloodvessels - this in turn means less of heat
loss so the effect will not go away as readily as in normal
tissues.

Clinical: I have seen some data on this but I don't have any
details available. One important question was: Should heat be
given before, during or after the X-ray/photon treatment? It
seems like the bottom line is: As closely in time as possible
-but preferably not more than 30 min. apart - if more than
two hours of a difference - any gain will probably be low
(I take these numbers out of my head). The other clinically
important issue is to check the temperature so that the whole
tumor volume gets enough of heat during enough time. From some
data shown at UCSF 5 years ago (Dr. W.C. Dewey - head of the
Radiation Oncology Research Laboratory gave a review talk)
- it was concluded that some European clinics probably have
been better controlling the temperature than their
American collegues - this seems to be very important. Some
of the data shown were very convincing (many patients) with
regard to the benefits of combined treatment for _some_ tumors.
I think the data were from melanomas, breast, colo/rectal, liver, prostate 
and cervical cancers (one of these categories was
probably not included -my brain cells are decaying). Dr. Dewey has written 
an excellent review article about the hyperthermia from a theoretical aspect 
- it was published in the Hyperthermia journal around 1993-94 I think.

The topic of micro/bloodvessels is complex also: If they are
closed the hypoxic tumor cells will tip over the edge and die
within say the order of 6 to 18 hours  but hypoxia/anoxia also protects 
against the effects of ionizing radiation. The hypoxic
cells can't divide because there is no oxygen (and glucose) to
push around the citric acid cycle to produce ATP. Killing the
oxic cells can cause the revival of the hypoxic cells (by making
them oxygenated). Please comment and fill in more details or
correct any thing I may have gotten wrong.

bjorn_cedervall@hotmail.com
Depts. Medical Radiation Biology & Medical Radiation Physics,
Karolinska Institutet, Box 260, S-171 76 Stockholm, Sweden
Fax: Int + 468 343525 (Med. Radiation Physics)
Website: http://www.geocities.com/WallStreet/Exchange/8256/
Any opinions expressed above are those of mine and may not necessarily 
coincide with those of others.




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