Anniversary professor, Dr. M. von Ardenne (to the 100 birthday of M. von Ardenne)
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Інститут експериментальної патології, онкології і радіобіології ім. Р.Є. Кавецького НАН України
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Chekhun, V.F. 2018-06-17T19:01:44Z 2018-06-17T19:01:44Z 2006 Anniversary professor, Dr. M. von Ardenne (to the 100 birthday of M. von Ardenne) / V.F. Chekhun // Experimental Oncology. — 2006. — Т. 28, № 4. — С. 329-332. — Бібліогр.: 22 назв. — англ. 1812-9269 https://nasplib.isofts.kiev.ua/handle/123456789/137927 en Інститут експериментальної патології, онкології і радіобіології ім. Р.Є. Кавецького НАН України Experimental Oncology Chronicle Anniversary professor, Dr. M. von Ardenne (to the 100 birthday of M. von Ardenne) Article published earlier |
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Anniversary professor, Dr. M. von Ardenne (to the 100 birthday of M. von Ardenne) / V.F. Chekhun // Experimental Oncology. — 2006. — Т. 28, № 4. — С. 329-332. — Бібліогр.: 22 назв. — англ. |
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Experimental Oncology ���� ��������� ����� ��ecem�er�� ������� ��������� ����� ��ecem�er�� ����ecem�er�� ����� ��� ���
In oncology it is continued to �e actual the pro�lem
of working out the effective and selective modificators
of action of conventional cytostatic means�� that has to
enhance their antitumor effect as well to decline their
toxic influence upon the normal tissue and organs.
Among the variety of modificators of traditional antitu-
mor therapy hyperthermia has a special place. Hyper-
thermia has �een known from Hippocrates time and
turned attention of the medical scientists in the end of
the 1�th century and received the principal new technical
and �iological impact in ���-th of the past century.
One of the initiators of the modern development of
hyperthermia was the outstanding scientist-physicist
Professor M. von Ardenne�� who has contri�ute much
for develop this promise and effective method�� espe-
cially as a whole �ody hyperthermic influence.
Institute of Experimental Pathology�� Oncology and
Radio�iology �IEPOR�� of National Academy of Sciences
of Ukraine �Kiev�� has started to work in thе hyperthermia
field since 1�7� owing to the proposition from famous
scientific triumvirate: Prof. M. von Ardenne�� Prof. B. Pa-
ton — President of National Academy of Sciences of
Ukraine and Prof. R. Kavetsky — founder of IEPOR. At
present the great interest is shown in Ukraine for hyper-
thermia�� especially for the using of local heating in the
treatment of patients with malignant tumors. Special
care was given to the pro�lem of tumor microphysiology
modulation with the aim to enhance the hyperthermia
efficacy. The 1�th International Symposium on clinical
Hyperthermia was held in Kiev on May�� 1��5.
In January ���7 M. von Ardenne will �e 1�� years
old. He was the promoter of the developing of the
hyperthermia pro�lems in our Institute that allow to
extend this promising method into com�ined treat-
ment of oncological patients in Ukraine�� and pay show
much respect to this great scientist the Editorial Board
propose some material devoting to this date.
Ardenne�� Manfred von
��.�1.1��7����.�5.1��7
Physicist and Cancer Researcher�� Prof. �r. h. c.
mult
1925–1926 two years study of physics�� chemistry and
mathematics at the university of Berlin
1928–1945 erection and managing of a private re-
search institute of electron physics in
Berlin
1945 mem�er of the German “Reichsfors-
chungsrat”��
1945–1955 nuclear physicist in the USSR leader of
a research institute for the development
of industrial technologies for isotope
separation in Sinop near Suchumi
1955–1990 CEO of the “Manfred von Ardenne Re-
search Institute” in �resden
1956 Professor at the Technical University of
�resden
1957–1989 mem�er of the “Research Council of the
G�R”
1961 chairman of the “Society of Medical
Electronics” of G�R
1963–1989 vice chairman of the “Kultur�und-Frak-
tion der Volkskammer der ��R”
1965 mem�er of the “Internationalis Astonau-
tica Academia” Pans
1991–1997 CEO of the “Von Ardenne Institut fur
Angewandte Medizimsche Forschung
Gm�H”
Main fields of research. Pioneer work in the field
of radio- and television engineering�� of electron- and
ion physics of �iomedical engineering�� first realization
ANNIVERSARY
PRofESSoR, DR. M. VoN ARDENNE
(to thE 100 bIRthDAY of M. VoN ARDENNE)
Exp Oncol �����
���� 4�� �������
ChRoNICLE
Received: October 20, 2006
*Correspondence: Е-mail: ceo@ardenne.de
��� Experimental Oncology ���� ��������� ����� ��ecem�er��
of an electronically wide�and amplifier�� development
of the electron �eam oscilloscope of compact design��
first realization of the full-electronically television�� in-
vention of the night vision equipment and X-ray image
converter�� invention and development of the scanning
electron microscope of high resolution�� R & � work
at the electron microscope for Siemens�� methods
to magnetically isotope separation�� electron �eam
multy cham�er melting furnace�� plasma torch with
finest plasma �eam of high density�� Oxygen Multistep
Therapy and development of the systemic Cancer
Multistep Therapy until the clinical application in con-
ventional incura�le patients suffered from cancer with
metastasis ���� patents in Germany and a�road.
Publications. More than �� scientific �ooks�� �eside
them “Funk-Ruf-Buch” �1��4���� “Verstärkermeßtechnik”
�1������� “�ie Kathodenstrahlröhre” �1����� 1��� engi����
“Fernsehempfang” �1��5�� 1���� engi���� “Elektronen-
Ü�ermikroskopie” �1�4��� 1�4� jap���� “Ta�ellen zur Ange-
wandten Kernphysik” �1�5������ “Ta�ellen der Elektronen-
physik�� lonenphysik und Ü�ermikroskopie” �1�5������
“Ta�ellen zur Angewandten Physik” �1������ 1�7�����
“Kre�s-Mehrschntt-Therapie” �1���7�� 1�71���� “Sauer-
stoff-Mehrschntt-Therapie” �1�7��� 1��1�� 1����� 1��7��
1��� engi�� “Systemische Kre�s-Mehrschntt-Therapie”
�1��7�� and more than 7�� further pu�lications.
Awards. Lei�niz-Medal of Prussian Academy of
Science �1�41���� State prize of USSR �1�47���� Stalin prize
of USSR �1�5����� �r. rer. nat. h. �. �� University of Greifs-�. �� University of Greifs-. �� University of Greifs-
wald �1�5����� National prizes of G�R �1�5���1���5����
�r. med. h. �. �� Medical Academy of �resden �1�7������. �� Medical Academy of �resden �1�7�����. �� Medical Academy of �resden �1�7�����
�r. paed. h. �. �� �resden College of Education �1��������. �� �resden College of Education �1�������. �� �resden College of Education �1�������
Wilhelm-Ostwald-Medal of Saxon Academy of Science
�1��5���� �iesel-medal of German Patent-Office �1�������
Fnednch von Schiller Prize �1������� honorary citizen
of city of �resden �1�����.
WhoLE-boDY hYPERthERMIA IN thE-SCoPE
of MANfRED VoN ARDENNE’S SYStEMIC
CANCER MULtIStEP thERAPY (SCMt)
(A short statement to the 100 birthday
of M. von Ardenne (1907–1997))
A. von Ardenne*
B. Van Ardenne Institute of Applied Medical
Research, Dresden, Germany
In 1��4 Otto War�urg �1����1�7��� pu�lished his
discovery of aero�e glycolysis of cancer cells [1].
In vitro he could proof and in 1���� confirm that tumor
tissue in contrast to normal tissue has in presence of
oxygen a prominent glycolytic meta�olism. Only retina
and �rain tissue show partly glycolysis under aero�e
conditions whereas in all other examined normal tis-
sues no such process was o�served. War�urg consid-
ered this peculiarity of cancer tissue as a “distur�ances
of the respiration” [�]. Aero�e glycolysis of the tumor
tissues causes the production of lactate�� which leads to
a reduction of the extracellulary pH-value in the tumor
tissue. This effect was o�served in human tumors�� too.
This phenomenon can �e used to differentiate normal
from tumor tissue [�]. The longstanding partnership
�etween von Ardenne and War�urg was intensified in
the �eginning of the sixties when von Ardenne develo-
ped ideas for cancer treatment �ased on War�urgs
experiments and findings of cancer cells growth.
�iscussions and experimental investigations were
intensified in such a way that War�urg convinced von
Ardenne to quit physics and concentrate on medicine��
especially to focus on cancer research [4].
fig. 1. Typical temperature-time course of systemic cancer
multistep therapy �sCMT��
As early as 1��5 Voegtiin o�served a decrease
of the pH-value in tumor tissue upon application
of glucose [5]. He measured the pH-value with a
pH-electrode on sarcomas and carcinomas of rat. To
our �est knowledge it was Naeslund�� who performed
first measurements on human gynecological tumors
under intravenous application of glucose in 1�5� [��].
Von Ardenne and his team in �resden investigated
the acidification of different tumor tissues also. They
proposed an “in vivo theory of glycolytic meta�olism
of tumors and their hyperacidification �y hypergly-
cemia” and explored the dynamic of selective hyper
acidification of tumors �y application of glucose [7�� �].
They discovered that no pH-decrease occurred dur-
ing glucose infusion over many hours in the skeletal
musculature and in the myocardium of rat [��� �]. Even
in the �rain of rats under such conditions ��� mM��l��
occurred no considera�le pH-reduction [1�]. This and
other o�servations lead to the conclusion that tumor
tissue can �e selectively over acidified.
Von Ardenne’s main goal — was to damage me-
tastasis of unknown localizations in the �ody. Thus he
had to ela�orate to what extend metastasis are over
acidified. Experimental data lead to the conclusion that
metastases even smaller then 1.5 mm� �approx 1���
cancer cells�� show a clear over acidification [11].
“Classical” denaturants of proteins are acid and��or
heat. This was the starting point for von Ardenne and his
co-worker of many years Reitnauer to ela�orate on the
synergy of hyperthermia and over acidification in 1����
in order to study cancer cell damage through thermo
sensi�ilization due to low pH-values [1�]. They discove-
red later on that this effect can even �e outperformed �y
extreme whole-�ody hyperthermia ��ody core tempera-
ture > 4�.5 °C��. Animal models provided experimental
Experimental Oncology ���� ��������� ����� ��ecem�er�� ��1���� ��������� ����� ��ecem�er�� ��1�ecem�er�� ��1�� ��1 ��1
data for selective tumor acidification. By increasing the
temperature of the tumor to 4� to 4� °C the pH-value in
such tissue decreased a�out �.5 pH-units [1�].
Usually meta�olism is strongly activated during
hyperthermia also in normal cells. A lack of oxygen
and glucose as �asic elements for the ATP-synthesis
would �e a disadvantage for normal cells in terms
of their sta�ility. This is one of the main reasons that
application of oxygen was implemented into the hy-
perthermia cancer therapy also [14]. This results lead
to the three main steps of systemic Cancer Multistep
Therapy �sCMT���� which are:
extreme whole-�ody hyperthermia
+ induced hyperglycemia
+ relative hyperoxemia
In 1�74 in the sCMT it was suggested already a
com�ination with cytostatics and radiotherapy [15].
The principle of the sCMT is represented �y those
three steps with selective la�ilization of cancer tis-
sue while sta�ilizing the healthy tissue. It should �e
complemented �y further selective steps�� damaging
the cancer tissues and sta�ilizing the normal tissues.
Over a period of �5 years many methods were inves-
tigated for systemic heating treatment of patients such
as water �athes�� extra corporal heat or high-frequency
hyperthermia. As the most promising method was found
water-filtered infrared-A heat radiation �wIRA�� in terms
of tolerance to human �odies simplicity and at the same
time potency. In wIRA a�out two thirds of the irradiation
energy is released in the corium and in deeper skin tis-
sue. Once the heat radiation reaches the vessel �ed of
the skin�� the �lood flow distri�utes the applied energy
through the whole organism. This principle is similar to
an outer �ody shell heating and allows a simple tem-
perature control of the outer �ody shell and the �ody
core. Such a whole-�ody hyperthermia system was
realized in the whole �ody hyperthermia device called
IRATHERM® ����. The temperature-time course of
sCMT �Fig. 1�� shows that it is possi�le to reach a final
temperature of over 4� °C and to apply a high dose of
heat within �� minutes [1��].
fig. 2. Individual evaluations related to diagnosis acc. To UICC
criteria in different tumor entites; 5% confidence interval for
nonP�-P� limit
In 1��� Manfred von Ardenne founded at his insti-
tute in �resden a research clinic for evaluation of sCMT
�uring a phase-I-study it was proofed that patients in
the stage of conventional uncontrolla�le progression
show a good systemic tolerance of sCMT with wIRA
hyperthermia with only “minimal side effects” [17]. Five
years later a research group at an university demon-
strated in a phase-I��II study that this therapy “does not
lead to any serious or sustained organ dysfunction and
can therefore �e regarded as a safe therapy” [1�].
In �resden’s sCMT clinic were given 4�� sGMT
one-time treatments in com�ination with adapted
chemotherapy to patients mostly with metastasis
in the stage of uncontrolla�le progression �etween
1����� and 1����5. The mean �ody-core temperature
had a value of 41.� °C ± �.� °C and the maximal �lood
glucose level one of �7.� ± �.7 mM��l during the sixty
minutes temperature plateau Fig. � shows the results
of different tumor entities evaluated on the �ase of
UICC criteria [1�].
Furthermore sponsored �y the “German Cancer
Aid” a prospective phase-I��II study was performed
on patients with metastatic colorectal cancer at the
University Hospital Virchow. Herein was tested a com-
�ination of sCMT and chemotherapy protocol �folic
acid + 5-Fluorouracil + Mitomycine-C��. The whole-
�ody hyperthermia was realized �y application of wIRA��
where the �ody-core temperature increased to 41.� °С
over ��� minutes as well as a 5�% enrichment of oxygen
through inhalation. The induced hyperglycemia had a
value of �� mM��l. �uring this study ten patients who
did not responded to three cycles of chemotherapy
were treated then with three cycles of sCMT plus the
same chemotherapy. Three patients responded with
partial remission �PR�� and in six patients progression of
the disease �P��� was prevented. Furthermore despite
the negative selection of patients in the control group
almost the same results were o�tained in the progres-
sion free survival in the control and-test group [��].
�uring a pilot study 1� patients with metastasized
adenocarcinomas ��reast�� n = 7�� ovarian�� n = 5��
colorectal�� n = 7�� were treated with sCMT plus che-
motherapy. All patients were refractory to standard
chemotherapy and lived in progression �P���. The result
of this study showed that nine patients reached a PR
and seven a No Chance �NC��. It was impossi�le to stop
progression in four patients [�1].
Two patients with refractory germ cell tumors were
treated three times with sCMT plus chemotherapy
�Ifosphamid + Car�oplatin + Etoposid��. In �oth cases
a PR was reached after therapy completed [��].
Besides the a�ove mentioned studies there are
three extreme whole-�ody hyperthermia phase-II
and two phase-III studies right now �������� on-going
in Germany. All these studies are performed under
induced hyperglycemia and relative hyperoxemia as
well as com�ined with chemotherapy. They all follow
the sCMT procedure.
Manfred von Ardenne is without dou�t one of the
most influential protagonist of hyperthermia in oncolo-
��� Experimental Oncology ���� ��������� ����� ��ecem�er��
gy�� who fought over 4� years for the vision that cancer
cells can selectively �e damaged in com�ination with
hyperthermia. Many groups are working today in the
area of hyperthermia with the focus on oncology�� what
is a proof for the rightness of his idea post mortem��
Manfred von Ardenne envisioned the sCMT in com�i-
nation with chemotherapy and��or radiotherapy as an
complementary method to conventional cancer thera-
pies. In his opinion the �est timing for this therapy was
an early stage of cancer�� prefera�ly perioperatively.
This will �e hopefully proven in the future.
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