The problem of malignant tumor growth. A fundamentally new solution

1. Oleksandr Shevchenko
Volodymyr Shevchenko
Viktor Shevchenko
The pr obl em
of malignant tumor growth
A f un dam e ntal l y new
sol ut i on
Kyiv
2009

2. УДК 616
ББК 55.6
Ш 38
Shevchenko O.V., Shevchenko Vol. O., Shevchenko V.O. The
problem of malignant tumor growth. A fundamentally new
solution. (Translated from Ukrainian). – 2009. – 72 р.
In 1970-ies in the former Soviet Union in Kyiv (Ukraine) an
efficacious immunological method for malignant tumors’ treatment
was created.
The complete recovery from transplanted and spontaneous
malignant tumors (even at the IVth stage of the disease) was
attained in a significant percent of cases in animals.
Attempts to treat patients with tumors by means of this method
yielded hopeful results.
The number of unique biological phenomena that had never
been described in science before were observed in individuals
cured by the new method:
• their blood serum gained therapeutic antitumor properties
that were manifested in allogenic and xenogenic systems;
• in the treated individuals their regenerative abilities have
considerably increased (up to organotypical regeneration);
• their organisms’ rejuvenescence as well as some other
phenomena were observed and the others.
In this book the scientists who participated in the research
conducted, describe the results obtained and provide them with
scientific explanation.
© Shevchenko O.V., Shevchenko Vol. O., Shevchenko V.O.
2009
Gnosis, 2009
ISBN 5-311-01319-2
2

3. Dedicated
to the blessed memory
of our relations: Zhana Shevchenko,
Sita Bezpalko and Svitlana Bezpalko,
who suffered from malignant tumors
3

4. Acknowledgement
The authors express a sincere gratitude:
• To the President of Ukraine’s adviser, Academician
Petro Tronko who, while holding an office of the First
Vice-Prime-Minister at the Government of Ukraine
rendered an organizing support for the research
described in this publication.
• To the director of Academician V.Komisarenko Scientific
Research Institute of Endocrinology and Metabolism, a
Corresponding Member at the Academy of Medical
Science of Ukraine Mykola Tronko, who participated in
the check experiment in 1970-ies.
• To Liubov Rachinska who was kind to provide us with
some materials from Vitali Rachinsky’s archives that
represent the results of the experiments conducted.
• To the politician Vasil Volga (Kyiv) and to the
businessman Evgeni Gavrilov (Moscow) for the
sponsor's support in publishing the present book.
• To Bela Men for translating the manuscript of the book
into English.
And also to everyone who rendered moral or organizing
assistance during all the period of theoretical and practical
researches as well as in preparing the book.
4

5. CONTENTS
INTRODUCTION 6
REVERSION OF MALIGNANT TUMOR
PROCESS: THE RESULTS OF 8
STUDIES AND OBSERVATIONS
CARRIED OUT
The results of malignant tumors’ treatment 8
in animals
The results of clinical observations 28
METHOD OF MAKING AND 36
APPLICATION OF ANTITUMOR DRUG
“NEOREVERSIN”
THEORY: A FUNDAMENTALLY NEW
VISION OF AN ORGANISM′S IMMUNE 38
REACTION IN PATHOGENESIS OF
MALIGNANT TUMORS
Specific immune reaction of organism as 38
initiator and promoter of carcinogenesis
Discussion 59
GENERAL CONCLUSIONS 67
THE PROSPECTS OF 68
IMPLEMENTATION
APPEAL 70
5

6. INTRODUCTION
In the early seventies of the last century Zoya
P.Uspenska, a kyivite phthisiologist, created an
immunological method for malignant tumors’ treatment,
based on placental extract, by means of which a significant
percent of cases of implanted and spontaneous malignant
tumors in animals at their generalization stage as well as in
oncology patients with neoplastic process at stage IV were
successfully completely cured.
The immunological antitumor drug applied acquired its
conventional title as Reversin.
In the middle of 1977 Z.Uspenska’s co-operation with the
authors of the present work began that had been going on in
different forms for 9 years (until Z.Uspenska’s death).
The results obtained aroused a wide interest in the circle
of physicians, biologists and some administrative authorities
(KGB of the former USSR, in particular).
Several competent commissions were set up to check the
findings of Z.Uspenska and her co-workers with the
participation of distinguished scientists: biologists,
immunologists and oncologists. Among them were the
world-known scientists (Academicians A.P.Avtsyn,
O.V.Baroyan and V.P.Komisarenko). They familiarized
themselves with the results of the work performed and gave
them a high scientific appreciation, having pointed out to the
good perspectives and the necessity to proceed with further
research in this direction.
Despite an active support of the above, there have never
been any financial or organizing measures taken that would
be necessary to expand the research in this sphere. In 1984
Z.Uspenska’s Laboratory was disbanded and the creative
team was broken up.
There were a number of reasons for that:
• First, the most serious obstacle to develop scientific
studies in this area was a striking lack of coincidence
between the results obtained and the scientific
notions existing at that time (and to a considerable
extent, at present) of the essence of oncology
process and the possible ways to influence it.
6

7. No theoretical concept has even been proposed, on
the grounds of which one could explain the whole
range of the unique results obtained.
• In the second place, all the researches on the
treatment of oncology diseases by the given method
were made secret at that time which excluded the
opportunity to familiarize scientific public at large in
the former USSR with them, to say nothing of the
foreign public.
• Thirdly, Z.Uspenska did not let anybody in on the
details of producing the Reversin drug, which
confined the opportunity to study its effect to one
laboratory only.
On May 29, 1986 Z.Uspenska died without revealing
the technology of the drug’s production.
Nevertheless, the research in this area was carried on by
the authors as we were the most closely associated with her
work, by conducting the experiments on animals,
participating in people’s treatment, etc.
The researches were aimed at restoring the drug’s
production technology as well as elaborating the theory of its
therapeutic effect.
As a result, the work of the informal scientific team,
consisting of Oleksandr Shevchenko, Volodymyr
Shevchenko and Viktor Shevchenko, has been
accomplished at the creation of an antitumor immunological
medicine, called “Neoreversin” which, according to the
preliminary experimental study results, has the properties
close to the Reversin drug used before by Z.Uspenska.
A new vision of the role played by an organism’s immune
system in shaping the malignant tumor process was
scientifically substantiated, in light of which an explanation of
most of the phenomena that had been observed in the
conducted research was made possible, and primarily, the
phenomenon of the reversion of malignant tumor process.
7

8. REVERSION OF MALIGNANT TUMOR PROCESS:
THE RESULTS OF STUDIES
AND OBSERVATIONS CARRIED OUT
THE RESULTS OF MALIGNANT TUMORS’
TREATMENT IN ANIMALS
The results of treating rabbits
Methods
Experimental study of the Reversin’s antitumor properties
was begun on rabbits with implanted Brown–Pearce
carcinoma.
Rabbits were administered a single subcutaneous
Reversin injection at the time when the signs of
generalization of the tumor process became apparently clear
i.e.: the loss of appetite and flesh, tumor metastatic nodes
being palpable in abdomen and under the skin or visualized
in eyes. Experiments on rabbits were conducted as from
1971 through 1980 in various research institutions. The
experiments’ results are summarized in the table shown
below (Table 1).
The efficacy of treatment was estimated by the following
criteria:
• the animals’ lifespan: the treatment was considered
efficient if the treated rabbits were still alive after the
last animal in the control group had died. Control
animals usually died during a month following the
tumor implantation;
• the animals’ physical status: the rabbits that had
recovered became more active, they had their
appetite resumed, the tumor nodes began
diminishing and finally completely disappeared. Also
the animals put on weight;
• on the basis of pathologicoanatomic examination,
carried out in different time periods since the
beginning of treatment, depending on the
undertaken task. In conducting the check tests all
the animals that survived (both the treated ones and
those untreated) were generally sacrificed.
8

9. Summary table of the results obtained in Reversin-treated
rabbits with implanted Brown–Pearce carcinoma.
Number of animals in a test Number of
group animals in a
Date of experiments conduction
(The animals were treated) control group
(The animals not
Place of the treated)
conducting Died
experiments
At the start of the
At the start of the
experiment
Died from tumor
treatment
Survived
Survived
Died for other
Died
reasons
Institute for
Oncology 1971
Problems of the and 51 37 11 3 25 __ 25
Academy of 1973.
Sciences of the
UkrSSR (Kyiv)
Institute of
Microbiology and 1971,
Virology of the 1972, 70 57 13 ___ 52 __ 52
Academy of 1973.
Sciences of the
UkrSSR (Kyiv)
Institute of
Molecular Biology 1976,
and Genetics of 1977, 98 71 16 11 44 2 42
the Academy of 1978,
Sciences of the 1979,
UkrSSR (Kyiv) 1980.
Institute of
Microbiology and
Epidemiology of 1977. 5 3 2 ___ 5 __ 5
the Academy of
Medical Sciences
of the USSR
(Moscow)
Total 244 168 42 14 126 2 124
9

10. It is seen from the Table, that 168 out of 224 treated
rabbits have recovered, that consist of 75%.
Out of 56 treated rabbits, witch were died in test group
the 14 animals differ from other. They died in between the
3rd and 4th months following the beginning of the treatment.
The purulent broncho- or pleuropneumonia were found at
their autopsy and no signs of tumor process.
If the 14 about mentioned rabbits were included into the
number of animals cured from tumors then the percentage of
recovery would increase to 81,3%.
10

11. The photographs of kidneys and liver of the
Reversin-treated rabbit slaughtered at an
intermediate stage of recovery from the malignant
tumor.
Fig 1. The kidneys affected by metastases of Brown-
Pearce carcinoma
The photograph shows small dark hollows in the center of
most of metastatic nodes. As it was proved by microscopic
examinations these were the zones of hemopoiesis.
11

12. Fig. 2. A section of the rabbit’s liver
In the center of metastatic nodes there are the very same
dark zones. Attracting attention is the fact that in the center
of the metastatic node, marked with a cross, there are only
three tumor fragments left and in between the liver tissue
structure can be clearly visible. Assumption: the metastases
cells were differentiated into the normal liver cells.
12

13. The results of the experiments conducted on rabbits
proved that after a single Reversin injection the
regression of tumor and its metastases occurred in the
organism, and anatomic integration as well as the
functions of the affected organs were completely
restored.
Pathologoanatomic examinations, including histological
tests conducted on rabbits by V.N. Rachinsky, a fellow-
worker of the Laboratory, give grounds to suggest that the
Brown – Pearce carcinoma tissues were transformed
after the treatment into normal tissues of the organ
wherein the primary and metastatic tumor nodes had
been present.
As it was shown in further research the blood serum
of the rabbits cured of Brown-Pearce carcinoma, some
time later (from 7 to 8 months) following the
administration of Reversin, had acquired therapeutic
antitumor properties that were manifested both in
allogenic and xenogenic systems.
This effect was extremely visibly displayed in the
experiment conducted by Oleksandr V. Shevchenko,
Volodymyr O. Shevchenko and Mykola D. Tronko at Kyiv
Scientific Research Institute of Endocrinology and
Metabolism.
On December 12, 1977 two Reversin-treated female
rabbits, being in the stage of recovery from Brown-Pearce
carcinoma, were selected for the experiment. By the
beginning of the experiment all the signs of the tumor
process had disappeared in both animals except for the
residual tumor metastases in the eyes as a greyish–white
formation occupying a part of the eye’s iris. The blood of a
rabbit, suffering from carcinoma, was dropped into the eyes
of both of the rabbits. On the third day after the blood
dropping all the signs of malignant process stimulation
emerged: the eyeballs began to increase and protrude out of
the eye sockets. On December 20, the antitumor serum was
started to be dropped into the eyes of one of the rabbits. A
week later the tumor regress became already visible.
Meanwhile the other rabbit’s progressive tumor continued to
grow. On January 7, 1978, the rabbit’s left eyeball projected
13

14. out of the eye socket by 2.5 cm and the right one – by 1,5
cm. The eye lashes were unable to cover the eyes.
That very day the other rabbit also started to undergo
treatment in the same fashion (by the serum dropping into its
eyes). Next day the dilated blood vessels were clearly
observed in both of its eyes, and some days later a vascular
plexus appeared in the shape of a ring around the necrosis
zone, formed at the apex of the enlarged left eyeball.
Antiblastic serum was dropped into the rabbits’ eyes for a
month’s time – first daily, then every second day and every
third day. A gradual resorption of tumors occurred in both
rabbits. And by the end of the 4th month since the beginning
of the treatment the tumors’ complete regression was
achieved. The eyeballs acquired their normal size and
shape. Both eyes of the first rabbit and the right eye of the
other one resumed their eyes’ normal look with an open
pupil. However, on the left eye of the other rabbit wherein
there was a large necrosis area, leukoma emerged.
Dynamics of the tumor regression was especially vivid to
occur on the left eye of the second rabbit. This dynamics is
presented in a series of figures shown below.
14

15. Fig 3. The 2nd day after the beginning of the serum
dropping
Both eyes of the rabbit are dramatically projecting out of
their eye sockets. The left one juts out by 2,5 cm. It shows a
tumor necrosis zone and the dilated blood vessel, which
hasn’t been observed prior to the beginning of the treatment.
15

16. Fig 4. The 6th treatment day. The view of the left eyeball
The blood vessels that became more strongly dilated can
be clearly observed. Necrosis area is also seen occupying
the entire eyeball zone. A demarcation line between the
tumor and the necrosis zone starts to be formed.
16

17. Fig 5. The 32nd day since the beginning of the treatment
The left eyeball has been significantly reduced in size
and acquired a cone-shaped form. On the cone top there
appeared a crust. An intensive vascularization of sclera
outer surface and reduction of the necrosis zone can be
clearly observed.
17

18. Fig 6. The 52nd day since the beginning of the treatment
The eyeball continues to diminish. There is an intensive
vascularization of sclera. The necrosis zone has been
reduced, the crust has disappeared.
18

19. Fig 7. The 66th day since the beginning of the treatment.
Side view
The necrosis zone has disappeared. The tumor has
acquired a compact shape and the closure of eye lashes
was made possible. Hypervascularization of the eye is still
preserved.
19

20. Fig 8. The 120th day after the beginning of the treatment
The tumor in the eye has completely disappeared. The
eyeball has its initial size and form restored, however on the
cornea where there was a necrosis zone, leukoma was
formed.
20

21. On the 120th day since the date of the treatment start no
indurations were identified in the rabbit’s abdomen at
palpation. The rabbit was in the normal physiologic
condition.
A year later after the experiment had been conducted the
above described rabbit was transferred to Moscow for
further investigations.
As it was founded out by the authors, no signs of the
undergone neoplastic process were detected at the
autopsy and histological analysis of the internals.
When exploring the eyeballs the presence of all the
anatomic constituents, characteristic of the normal eye,
was stated. Out of pathologic abnormalities there was
keratoleukoma.
An impressive result of the experiment was also that the
regression of the tumor occurred in the setting of a sharp
increase in its vascularization.
New biological phenomena found out in experiments
on rabbits
1. The phenomenon of complete reversion of the
malignant tumor process from its generalization
stage.
2. The effect of post-convalescent antitumor
resistibility. The essence of the phenomenon lies in
that the rabbits which have been cured of Brown-
Pearce carcinoma by means of Reversin can’t
repeatedly take on this tumor.
3. The phenomenon of the blood serum antiblastic
activity in rabbits cured of Brown-Pearce
carcinoma by means of Reversin.
4. The phenomenon of malignant tumor regression
in the setting of a sharp increase in its
vascularization.
21

22. The results of treating horses
Experiment description
The Reversin drug was also applied to treat 3 horses
(two stallions and a mare), suffering from malignant
neoplasms – melanosarcoma and melanoblastomatosis. (As
is known from the literature, melanotic tumors can be often
found in horses of grey breed.)
A stallion “Vodiy”, born in 1961, of the Orlov trotter breed,
was examined on 20.05.1973 by the Veterinary
Commission, headed by Professor I.O. Povazhenko, being
in charge of the Chair of Surgery at Ukrainian Agricultural
Academy. A focus of melanosarcoma was detected in the
horse in the left prescapular region being two fists size, a
melanosarcoma focus on the penis a hen egg size, and a
focus of melanosarcoma near the anus being a wall-nut size.
On the basis of the disease symptoms found the
Commission arrived at the conclusion that it was inexpedient
to treat the stallion and it was to be rejected as defective.
At that time a stallion “Amper”, born in 1961, of the Orlov
trotter breed was also rejected as defective because of
melanosarcoma disease. A great amount of
melanoblastomatosis nodes were identified near the anus, a
pigeon-egg to a wall-nut size, as well as in the region of the
spur vein on the left and in the area of the penis a plum size.
On 14.09.1973 both stallions underwent the treatment
with Reversin.
On 4.05.1977 Reversin was also administered to treat a
mare “Pokrova”, born in 1958, of the Orlov trotter breed,
which was rejected as defective because of
melanoblastomatosis disease in the areas of the anus and
udder in accordance with the Statement of 14.04.1977.
Treatment results
On March 24, 1979 all the three horses were examined
by the same Commission that had rejected them as
defective. The Commission came to the following
conclusion:
1. The stallion “Vodiy” is clinically healthy. At the seat of
the tumor in the left prescapular region there is a small
induration of 5 x 7cm size remained, protruding a bit
22

23. over the skin surface. Near the anus there is an
induration of 2.5 x 2.5cm having a hollow in the center.
The tumor nodes on the penis and in the scapula zone
have completely resolved.
2. The stallion “Amper” is clinically healthy. Near the anus
the residues of three nodes 0.5x1.0 cm in size can be
palpated. The tumor nodes in the area of the penis and
the spur vein are completely resolved.
3. The mare “Pokrova” – is in a good state. The tumor
nodes near the anus, the udder and on the right of the
mandible have completely disappeared. Edemas in the
abdomen and udder region have gone. The mare is
clinically healthy.
The follow-up term for the stallions made up 5 years, for
the mare was 2 years. The Commission made a conclusion
of the efficacy of the method applied for the treatment of
malignant neoplasms in horses.
It is seen from the above mentioned that complete
reversion of the neoplastic process from its generalization
stage can be achieved in horses as well by means of
Reversin.
Biological phenomena, observed in treating horses
Just like in the case with rabbits some concomitant
phenomena were also observed with horses cured.
The horses got rejuvenated which was displayed in their
renewed capacity for work (they started to be used again for
agricultural works to the full) and in their resumed sexual
activity, gone out already by the beginning of the treatment
as well as in their restored pelage colouring typical to young
specimens: dapple - gray, three months after the treatment.
This pattern disappears in old horses. They become
uniformly light-gray.
This phenomenon, i.e. the organism’s rejuvenescence in
horses cured from malignant tumors, can be the basis for
the assumption to be made that their lifespan could surpass
their average indexes. Speaking in favour of this assumption
is the fact that the above described horses when delivered
for slaughter (as they reached an average age for the Orlov
trotter equal to 22 years old) were still strong and capable of
working with sexual activity preserved.
23

24. The results of treating mice
In the experiments carried out on mice, Erlich carcinoma,
a classic version of the malignant tumor disease served as a
model. A solid tumor process was induced by subcutaneous
inoculation in the animals’ back or femur zones of a cancer
cells suspension in the form of a peritoneal exudate derived
from the abdominal cavity of mice, suffering from ascitic type
of carcinoma. Prior to the injection the exudate was diluted
by a sterile physiologic salt solution with 1:1 ratio. The
experiments were conducted on white, non-thoroughbred
animals, as well as on the mice of CBA line. The animals’
treatment started when a tumor node no less than 1cm size
in diameter appeared in the place of the cancer cells
inoculation.
The attempts to treat mice suffering from the solid
carcinoma by means of Reversin yielded no positive results.
However, the treatment of mice with antitumor blood serum
of the rabbits, cured by means of Reversin, was a success.
The serum was administered parenterally to mice. The
tumor ceased to be palpable in the experimental animals
during the interval between the 20th and 30th days since the
beginning of the treatment.
Totally 185 mice were used in the experiments. The
recovery of animals occurred in 40 through 60%. Being
based upon the findings one can make two conclusions:
• the first one is that mice just like rabbits can also be
treated for malignant tumor process by the new
method;
• the second one is that in so far as overcoming the
tumor process in mice was attained by means of the
rabbits’ serum it indicates to the ability of the latter to
display antitumor properties not only in allogenic but
also in xenogenic systems.
Phenomena observed in experiments on mice
1. The phenomenon of an organism’s expanded
regenerative abilities.
It was found out on mice exactly that the range of
regeneration processes in animals, cured of malignant
24

25. tumor, can be strongly expanded right up to the possibility of
organotypical regeneration.
This phenomenon was not anticipated and it was
discovered quite occasionally. A group of mice cured of
tumor that were regarded as being worked off, were kept for
several months in a vivarium for the purpose of their
possible use in other experiments.
During this time period the mice’s tail ends, cut off to
collect blood during the experiment, were noticed to grow.
The procedure of collecting blood from mice’s tails after their
ends being amputated is a routine method widely used all
over the world. However, nobody has ever observed the cut
off tail parts being regenerated. Thorough investigations
proved that this phenomenon was a result of the animals’
recovery from the malignant tumor. A histological analysis of
the regenerated tails’ parts was performed. A histological
preparation was made in Professor Sementsov’s Laboratory
at Burdenko Military Hospital (in Moscow). The Laboratory
comments weren’t preserved but those histological
preparations were also studied by K.M. Tantsyura, Assistant
Professor at Pathoanatomy Department of Kiev Medical
Institute. The expert testified to the fact that “in the referred
material the bone regeneration occurred, which passed
through the cartilage stage; the shaping of bone beams was
observed with the presence of bone marrow cavities filled
with marrow”.
The phenomenon of a tail’s end regeneration has also
been reproduced in Kyiv Scientific Research Institute of
Endocrinology and Metabolism. Its description is shown
below.
Description of the experiment on reproducing the
phenomenon of an amputated tail’s part regeneration in
mice cured of Erlich carcinoma by immunological methods.
In March 1978 Z.P. Uspenska, head of the Laboratory for
Cell Protection Mechanisms at the Institute of Molecular
Biology attached to the Academy of Science of the UkrSSR,
proposed us, O.V.Shevchenko, head of the Laboratory for
Experimental Pharmacotherapy at Kyiv Scientific Research
Institute of Endocrinology and Metabolism attached to the
Ministry of Health of the UkrSSR, M.D.Tronko, academic
25

26. secretary of the same Institute, a senior research worker at
the Laboratory for Pathophysiology and G.F. Matvienko, a
veterinary physician being in charge of the Vivarium at the
same institute, to conduct a check experiment on
reproducibility of the phenomenon of an amputated tail’s part
regeneration in mice, cured of a solid Erlich carcinoma type.
To conduct the experiment an antitumor serum preparation
was obtained from the Laboratory for Cell Protection
Mechanisms by the Pharmacotherapy Laboratory
represented by O.V.Shevchenko.
On 15.03.1978 four non-thoroughbred white female mice
weighing 16 to 18gr. were subcutaneously inoculated in the
femur area with Erlich carcinoma in the form of 0.2 ml 50%
ascitic fluid derived from the mice suffering from an ascitic
type of this tumor. The treatment was started 12 days later
when tumors of 1x1.5 cm size developed in the mice in the
place of inoculation. Antitumor drug was administered
subcutaneously of 1.0 ml every second day right up to the
total tumor regression (as determined by palpation). The
tumors in the experimental animals ceased to be determined
by palpation during the interval between the 20th and 30th
days since the beginning of the treatment. At the moment,
when the tumor tended clearly to diminish, the tails’ parts 1.5
to 2cm long were amputated in those four animals by means
of a sharp scalpel. Hemostasis was made by means of a
concentrated Kalii permanganas solution.
Over a month’s time the wounds got healed by the
secondary intention and covered with epithelium. During the
next two months of follow-up an outward appearance of the
tails’ stump wasn’t notably changed. The experiment was
considered to have failed – a tail regeneration phenomenon
was not reproduced. Therefore three of four experimental
mice were used for other experiments but one mouse still
remained. Soon owing to the force of some circumstances
its distal vertebra stripped itself in the place of amputation.
Some time later next to the mummified vertebra there
appeared a projection that began to extend. By the end of
November, i.e. 8 months later after the amputation, the
projection took shape of a tail’s regenerate though a bit
deformed but with all the signs pertaining to the organ:
epithelial scales, mobility and hair.
26

27. Thus, a phenomenon of the amputated tail’s part
regeneration was fixed by us on one adult mouse, cured of
Erlich carcinoma. The picture with the tail‘s regenerate is
shown below.
Fig 9. Regeneration of the tail’s end in a mouse cured of
Erlich carcinoma by the immunological method
This experiment’s result has one more peculiarity. As is
seen from the picture the growth of the regenerate occurred
not out of the amputation surface but sideways which
resembled the sprouting of a plant branch out of a side bud.
The cured mouse with the irregular tail’s end
regeneration was transferred to Moscow for further
investigation.
The results of the experiments carried out at Kyiv
Scientific Research Institute of Endocrinology and
Metabolism were reported to the President of the UkrSSR
Academy of Science by the Director of the Institute -
Academician V.P. Komisarenko.
2. The phenomenon of lifespan extension in the cured
animals
Alongside with the phenomenon of expanding an
organism’s regenerative capability in the mice cured of the
implanted Erlich carcinoma, a tendency to extend their
lifespan was also established (in the average of up to 2.5
years against 1.5 years in a control group).
The implantation of tumor was performed according to
the generally accepted methods.
27

28. THE RESULTS OF CLINICAL OBSERVATIONS
After the Reversin and antitumor serum atoxicity was
proved by injecting a 10-fold therapeutic dose into intact
animals as well as one therapeutic dose into a healthy
human (to Z.P. Uspenska) the antitumor treatment by the
worked out method was applied to some of the patients of
clinical group IV, with a blastomic process at stage IV on
request of the patients themselves or their relatives.
The diagnosis of the disease used to be always verified
in specialized oncology institutions.
A positive result was established in both female and male
patients with malignant tumors of various nature
(carcinomas and sarcomas) and diverse localization
(mammary gland, genitals, thyroid gland, stomach,
esophagus, lungs, testes and others).
Presented below is a very condensed and schematic
description of a generalized picture of clinical manifestations
in organisms of the patients suffering from malignant tumors
to the Reversin and antitumor serum injections.
Clinical picture of the treatment process in patients with
generalized malignant tumors
On injecting the antitumor Reversin drug into a patient’s
organism there takes place a specific clinical reaction,
wherein the following periods can be marked out.
Periods of reactions
The period of primary reactions
The primary reactions to the Reversin drug’s
subcutaneous or intramuscular injection are of a vascular
nature.
Several minutes later hyperemia emerges around the
place of injection. Following it the blushing of cheeks, nose,
ears, palms and all the visible mucosa as well as that of the
nail beds and postoperative scars was generally observed.
Te patient at this time can have caumesthesia on the skin
of the face.
28

29. Sometimes there occurred reduction or change in the
character of pain sensations if they had been present prior to
the treatment start.
Following hyperemia around the point of the skin
puncture there emerges a papule of 3 to 15 mm in diameter.
It normally disappears 10 to 15 min later while hyperemia
may last for some hours more, though directly in the point of
a puncture it may last up to several days.
The period of secondary reactions
This period is conditioned by the processes proceeding in
the area of tumor nodes’ localization as well as by the
general reactions. It is distinguished by a significant
polymorphism of symptoms, the presence and
expressiveness of which depend on the tumor size, its
location and metastases as well as on patient’s state at the
moment of the treatment start and the presence of
concomitant diseases.
The following symptoms can be observed during this
period.
In the setting of normal or somewhat increased body
temperature in patients there appears a feeling of “hot flush”
or fever (sometimes very high) being localized in the tumor
effected areas.
These phenomena are associated with xerostomia and
thirst. Sometimes there appears a subjective feeling of a
higher temperature in the entire body. Physically the
temperature doesn’t exceed 37,5°C.
Specific for the second period are also changes in the
pain syndrome.
The nature of pain sensations is generally changed after
administering the Reversin drug. Sometimes the decrease in
pain or even its complete disappearance occurs. On the
contrary the pain can sometimes rise which may be
associated with edema occurring periodically and resulting in
compression of organs or nerve trunks. Typical of these
pains is their periodical nature.
During this period mucosa and skin hypersensitivity to
different mechanical, chemical and thermal stimuli can be
observed.
29

30. During the recovery period a “creeping” sensation
appears periodically in the region of tumor nodes.
If the tumor process was widely spread one could
observe a temporary impairment of the patients’ general
state in the second period which was likely to be associated
with the resolution of necrosis masses that were always
present in large tumor nodes.
In this, general weakness, nausea, vomiting, a feeling of
rheumatic pain all over the body and constipations
alternating with diarrhea can be observed.
In the setting of polymorphism of the symptoms specific
to the second period of reaction some cyclic recurrence of
their manifestations can be traced.
First (during the first days) they were observed to occur
some cycles a day. Then they appeared rarer.
The cyclic reaction may be observed to occur
simultaneously in all the tumor effected areas, though it can
first cover some zones only, moving on to the others in a
due course. The second version of the reaction course is
more favourable.
With the favourable progress of the process the above
mentioned symptoms’ manifestations go gradually out and
then disappear completely. The reaction passes on to the
3rd period - that of the complete recuperation lasting for
about a year, typical of which is the absence of any special
symptoms not to mention the enormous increase in appetite
that turns sometimes into a “gargantuan” appetite (the
patient eats up much food, he even dreams about it at night,
especially about the forbidden foods). Despite the quality
restricted diet the body weight sometimes augments very
quickly and can exceed by far the initial weight coming to
norm during the following years only.
During a year’s period there occurs complete
disappearance of the tumor and its metastases as well
as substitution of the tumor-induced defects and also of
all the tissues with the corresponding full value tissues
in morphological and functional respect (in the liver - by
the hepatic tissue, in the lungs – by the pulmonary
tissue, in the skin – by the cutaneous tissue, etc.).
30

31. Changes in an organism’s responsiveness during
the treatment process
According to the literature data as well as to our
observations the responsiveness of patients with expanded
tumor lesion is dramatically deteriorated which is shown in
the inhibited inflammatory reaction, in particular. Various
dermal abscesses disappear, in particular.
A favourable sign testifying to an increase of the
responsiveness in a tumor-host (observed normally 2 to 5
weeks later after the beginning of the treatment in most of
the patients) was the eruption of abscesses on the entire
body (as from a single one to dozens of them). The
abscesses soon disappeared.
The patients during this period became hypersensitive to
infectious diseases of cold type, in particular. The
progression of infection may lead to the reaction
“breakdown” which will be commented on later.
Further on with the favourable reaction progress the
organism’s responsiveness gets gradually normalized.
In addition, during the patients’ treatment a problem of
symptomatic therapy arises. In the course of antitumor
treatment the organism’s sensitivity to the whole range of
medicines (cardiac glycosides, nitrates etc.) turned out to
grow dramatically. The above preparations as administered
even in the usual therapeutic doses could cause very severe
complications.
31

32. Biological phenomena observed in clinic
1. The phenomenon of curability from malignant tumor
at the generalization stage of the process
Clinical observations have established the opportunity
for the patients of clinical group IV suffering from
malignant tumors at the generalization stage of the
process to completely recover which is confirmed by the
conclusion of the authoritative medical institutions.
2. The phenomenon of the complete tissular and
organotypical regeneration of the tumor- affected
organs and tissues
After the treatment in the sites of the tumor-affected
areas of organs and tissues, a full - value tissue in
anatomic and physiologic respects was formed which
was confirmed by various investigation methods being
applied in clinic.
3. The phenomenon of an organism’s rejuvenescence
With some elderly patients cured of malignant tumors,
the grey of their hair was observed to disappear;
muscles’ strength was observed to augment as well as
skin turgor was observed to rise and the working
capability to increase, etc.
32

33. The reaction – associated complications
The above described reaction appeared in almost all of
the patients in response to the drugs injection. It was more
pronounced after the Reversin injection. In case of the
serum injection its manifestations were considerably less.
However, not all the attempts to treat people were
successful.
In the main, two complications accounted for the failure:
• the first one is a too violent progress of the reaction
which was determined by its generalization;
• the second one is “a breakdown” of the reaction.
1. Generalization of the reaction
With the tumor lesion being extremely massive the
reaction may proceed rapidly and violently. In patients there
appeared a state resembling the picture of kinin shock:
mental blankness, hemorrhage out of all the mucousa and
death.
This complication was observed rarely, it was stated only
in two incidents and only after the Reversin injection.
2. “Breakdown“ of the reaction
The most frequent reason for the treatment inefficacy
was a complication, entitled as the reaction “breakdown”.
By this term we define a disease course during which
positive tendencies in the development of the recovery
process terminated allowing the negative ones to occur, that
are characteristic of the resumption in the disease process.
After the reaction “breakdown” the tumor growth assumes
a progressive character which leads to a patient’s death.
Clinically the “breakdown” of the reaction is determined
by disappearance of the symptoms typical of the favourable
flow of the reaction and by recurrence of a set of symptoms
characteristic of the progressing tumor disease.
The “breakdown” often happened when the patient failed
to keep to the diet; it occurred as well without any visible
reasons when there was a flaccid (hypoergic) reaction
process.
An early laboratory sign of the unfavourable reaction
process is a decrease (sometimes dramatic) in the
percentage of lymphocytes’ content in peripheral blood.
33

34. After the reaction “breakdown” the character of
relationship between the host and the tumor returns to the
state similar to one that existed prior to the beginning of the
treatment. The similar state is but not the identical one.
Testifying to this is the fact that attempts to resume the
reaction by the repeated Reversin drug or serum injection
failed.
Prevention of the reaction-related complications
Prevention of the reaction generalization
In so far as generalization of the reaction was established
in the cases of Reversin application only and it was not
observed in any other case with serum treatment it is
advisable to use serum in case of massive tumor lesion.
Prevention of the reaction “breakdown”
1. Prevention of contacts with the infected patients
It is achieved by simple quarantine measures.
2. The use of special diet
It was established in the experiments on animals that for
a year following the antitumor drug injection their food
should not contain any components of the animal origin.
The inclusion of these kinds of products even in
microdoses into the rabbits’ ration during the treatment
process led to their death as a result of stimulation of
blastomatous process.
In the course of further research a special diet has been
worked out. The strict keeping to the diet is compulsory in
the treatment of all the experimental animals as well as
humans.
In our opinion it was the very factor of failure to keep to
the diet that accounted for the reaction “breakdown” in the
patients’ treatment. The difficulty in keeping to the diet was
that all the patients in all the above cases stayed at home in
family surroundings the members of which mostly didn’t alter
their traditional way of having meals.
34

35. Indications and contra-indications for applying the
new treatment method
Indications
Indications to apply the method were worded with regard
to the conditions wherein the laboratory employees could
have an opportunity to perform the treatment.
Medical indications:
the presence of the diagnosis of malignant tumor process
of any nature and localization at stage IV of its development,
verified in an official medical institution.
Social and ethic conditions:
- refusal by the official medicine to perform the patient’s
further pathogenetic treatment (transition to symptomatic
one only);
- availability of a patient’s consent;
- availability of the patient’s relatives consent.
Contra-indications
Absolute medical contra-indication to apply the worked
out treatment method is a previous chemotherapy.
Of all the above stated, one can make a conclusion
that the clinical observations carried out, despite the
patients’ incomplete clinical examination during the
treatment, strongly testify to the antitumoral therapeutic
efficacy of both Reversin and antitumor serum.
35

36. METHOD OF MAKING AND
APPLICATION OF ANTITUMOR DRUG
“NEOREVERSIN”
Being based upon:
• the laborious gleaning and analysis of
separate results obtained in the research that
took place in 70-ies through 80-ies of the last
century;
• the theory of pathogenesis of malignant
tumor process created by us,
we tried to reproduce the formula of the Reversin
drug and its application technology.
In view of the fact that the original Reversin’s
formula and the method of its application have been
lost, we can’t guarantee the identity of the Reversin
drug and its application technology with the
Neoreversin drug created by us and the method of its
application described.
For making of the preparation “Neoreversin” it is
necessary to have two components: extract of placenta and
blood of cancer bearing hosts.
Method of making an extract of human placenta
The procedure of making a placental extract is carried out
with the greatest observance of aseptic rules.
Human placenta is obtained from natural physiological or
artificial cesarean deliveries (the latter is better).
The placenta is minced in slices approximately of 2 – 3 sm3
in size (the size of parts has no importance).
The placenta is placed in a sterile vessel. Then there the
sterile physiological solution is added in amount 0,5-1,0
parts in relation to placenta weight.
The vessel with placenta is placed in a refrigerator at
+20С – +40С for 3–4 days.
36

37. Media (placental extract) is harvested and kept at +20С –
0
+4 С not longer than 3 days.
Method of making antitumor preparation
“Neoreversin” and its application to rabbits
Preparation of the animals for treatment by
“Neoreversin”
This preparation consists only in performance of
autohemoterapy once a day during three days.
Method of making “Neoreversin”
The preparation “Neoreversin” is an active biological
complex which is produced directly before its use (ex
tempore).
Preparation of the complex
The extract of placenta is taken in a syringe (1,3 – 1,6 ml)
and then in the same syringe the blood of cancer bearing
rabbit (0,7 – 0,4 ml) is added. The components are mixed by
the air–bead.
This bead is left in the syringe.
The mixture is stored in a syringe for 30–40 minutes.
The criterion of optimal correlation between the
components is transformations of the mixture in a syringe
into gel in an interval of time from 10 to 20 minutes of
exposition.
Mode of application of “Neoreversin”
The “Neoreversin” is injectied into the rabbit body by
hypodermic or intramuscular injection in amount of 2 – 2,5
ml per one animal.
After the treatment the rabbits should be at complete rest.
The diet – exclusively plant food.
37

38. THEORY:
A FUNDAMENTALLY NEW VISION
OF ORGANISM'S IMMUNE REACTION
IN PATHOGENESIS OF MALIGNANT
TUMORS
Oleksandr V. Shevchenko, Vol. O. Shevchenko,
V.O.Shevchenko
SPECIFIC IMMUNE REACTION OF ORGANISM AS
INITIATOR AND PROMOTER OF CARCINOGENESIS 1
(hypothesis)
Having considered the published data, but devoid of
rational explanation in due time, the authors put forward a
hypothesis about the decisive role of an organism’s specific
immune reaction in pathogenesis of malignant tumor
process. The hypothesis was shown not to contradict a
contemporary vision of the mechanism of malignant tumor
development. It was concluded that the induction in tumor-
hosts of immune tolerance to tumor antigens makes
retransformation of tumor cells to normal ones possible.
Key words: tumors, immune reaction
One of the principal tasks of a theoretical
study in any field of knowledge consists
in determining that standpoint, from which
the object of research could be revealed
in the simplest way possible.
D.Gibbs
1
“Journal of Medical Science Academy of Ukraine”, 2004, v.10,
№1. – p.50-64 UDC 616-006.04:612.017.1 (Recommended by
Corresponding Member of MSA, Ukraine V.A.Mikhnyov)
38

39. The problem of immunologic interrelations between
malignant tumors and host is very complicated and intricate.
More than a hundred years have passed since the
experiment showed the possibility for cancer immune
prevention, but the creation of highly efficacious
immunologic modes to treat malignant tumors is still waiting
for its time to come.
When starting to present our vision on one of the
immunological approaches to solving the problem of
malignant tumor growth we find it necessary to submit a
concise description of its general picture while dwelling at
some greater length on those chapters only which are
directly associated with the idea asserted in this publication.
As back as the early 20th century S. Jensen published
his work wherein he, being based upon the results obtained
in the performed research, stated the idea concerning the
possibility to artificially create an active immunity to
malignant tumors [29]. Soon after, P.Erlich with his
colleagues joined in studying this problem [40]. In the
fashion analogous to the methods, applied in bacteriology,
they immunized animals with avirulent tumor material,
developing their resistance to inoculation of already virulent
tumors. However, the interest to the research in this area
decreased and up to the middle of the last century only
isolated reports appeared about the works dedicated to
studies of the immunity to tumors. It’s not until the works by
E.Foley [28], R.Prehn and J.Main [37], R.Beldwin [21] and
others had been published that the researches in the field of
tumor immunology were dramatically activated. Using auto-
and syngeneic systems, researchers clearly identified the
presence of the phenomenon of antitumor immunity. The
animals, previously injected with inactivated malignant tumor
cells, gained resistance to inoculations with the living tumor
material. Almost all the elements (humoral as well as cellular
ones) of the immune system were found, and not only in
experiments but also in clinic, to be involved in the formation
of antitumor immune reaction. However this mechanism
doesn’t ensure any protection against malignant tumor
growth in natural conditions. This is associated with a
number of circumstances. As it has become clear, along with
the evolvement of immune reactions having an antitumor
39

40. trend, their blocking mechanisms come into action. Apart
from this, there’s one more phenomenon making the
situation much more complicated – it is immunostimulation
of tumor growth (this phenomenon will be regarded in detail
further on). Such interweaving of the processes, having
different trends, is apparently responsible for the current
state of the immunotherapy, when it is capable of
performing, and not always though, a secondary role only.
To make sure that it is really so, one can open the last
edition of the capital manual on the treatment of malignant
tumors “Cancer Medicine” [20]. The following is said there
about the possibilities of the immunotherapy: “…favorable
results of the immunotherapy can be observed only in
patients having microscopic manifestations of the disease
provided that the adjuvants were applied after all the clinical
tumor manifestations had been eradicated by means of
traditional treatment methods”.
Nowadays titanic efforts are being made to boost an
organism’s immune reaction to the efficient level by means
of antitumor vaccines. A great number of research
institutions and firms are engaged in creating them. [19, 26,
27, 31, 32, 41]. However, not all assess unambiguously the
prospects of this direction. So, R. Prehn, a lead theorist in
the area of antitumor immunity problems, for example, treats
it with caution, admitting though the perspective of antitumor
vaccination with embryonic tissues [34].
When analyzing pathogenesis of malignant tumors, we
paid attention to the phenomenon of malignant
transformation of embryonic cells transplanted into ectopic
(extrauterine) sites of adult syngeneic animals. This
phenomenon has not received any unified theoretical
interpretation as yet.
Its exceptionality consists in the fact that embryonic grafts
undergo malignant transformation without any carcinogenic
impacts, i.e. there takes place carcinogenesis without
carcinogens. This fact became the basis for shaping our
views as to the role of an organism's immune reaction in
carcinogenesis which differed from those generally
accepted.
In the late 70-ies and early 80-ies of the 19th century
J.Cohnheim’s views concerning the origin of malignant
40

41. neoplasms were shaped [25]. According to J.Cohnheim
malignant tumors can be developed either from the
remaining embryonic tissues that happened to be among the
definitive tissues of the same histogenesis but, due to some
reasons, were not involved in the normal tissue building
process, or from the embryonic residues, transferred to
another site, which appear to become a heterotopic object
and therefore are not involved into intratissular interrelations.
These embryonic residues give rise to neoplastic growth. In
order to prove or disprove this hypothesis the embryonic
material (tissues or embryos’ parts) was transplanted into
adult animals however there was no growth of tumors from
them. But when embryonic cells, isolated from the embryos
in pre-implantation period, were implanted into the
extrauterine sites of adult syngeneic animals, they were
naturally transformed into malignant ones. A well-known
expert on the problem of malignant cells’ differentiation,
I.Shvemberger spoke on the subject as follows: “The fact
that no tumors develop in the case of the ectopic
transplantation of definitive tissues allows the ectopic grafts’
malignant transformation from embryonic tissues to be
assessed as a particular case of carcinogenesis, that by
etiology, pathogenesis and prognosis should be considered
individually” [15]. However, the author of the work doesn’t go
beyond these recommendations.
In the literature of the following years we haven’t found
any attempts to provide this phenomenon with any
theoretical interpretation either. Although in our opinion it
suggests the existence of some intrinsic cause for
transformation of embryonic cells into malignant ones. It is
unclear whether this cause can have any relationship to
other cases of carcinogenesis. It can’t be excluded that
determination of the nature of this intrinsic factor and
induction of neoplastic transformation will enable one to find
answers to some other questions as to the mechanism of
malignant tumors origin.
About 30 years ago G. Svet-Moldavsky [9] explained this
phenomenon as follows: in embryos there exist some
powerful cellular and humoral factors regulating the
embryonic cells capacity to grow and differentiate. They are
absent in an adult organism. If embryonic cells are
41

42. reproduced in the organism where there are no factors
regulating their growth and differentiation, they’ll become
malignant.
In a theoretical study “Embryonic Properties of Tumor
Cells: Facts and Hypotheses” Ya. Ehrenpreis [18], touching
upon the problem of extrauterine embryonic grafts’
neoplastic transformation, points out, that the reason for it is
non-embryonic conditions of such grafts cells’ existence but
he doesn’t specify what factor of these conditions exactly is
directly responsible for neoplastic transformation. And on the
basis of his monograph “Contemporary concepts of tumor
growth” [17] only, published in 1987, does it appear that he,
like G. Svet-Moldavsky as well, sees the reason for such
transformation in the absence of embryonic inductors of
differentiation in the adult organism. Such ideas are quite
logical. Actually in embryos normally not only does the
growth and differentiation of embryo’s own cells occur but so
does the differentiation of cancerous cells transplanted into
the embryo [30]. However the blank side in these
hypotheses is the fact that many attempts to isolate the
differentiation factors out of embryos yielded no convincing
results. Embryonic extracts, being not infrequently far from
inhibiting, have even stimulated neoplasias’ growth.
But rightful can also be another assumption, viz.: in adult
organisms there’s a certain factor that induces malignant
transformations of embryonic cells which is absent in
embryos. What kind of factor can it be? One of the
distinctions between embryo and an adult organism is the
presence in the latter of the immune-reacting system and its
absence in embryos. So, perhaps, the very system itself
contributes to the fact that cells, having embryonic
properties, become malignant while being transplanted into
an adult organism? We are aware of some paradoxical
character of such an assumption since usually the effects of
an entirely opposite nature are associated with the immune
system, as It is the one, which, in compliance with the theory
of immune surveillance, resists the development of
malignant neoplasms. Nevertheless, it is well known that
immune reactions in an organism are being far from playing
always a protective role. A lot of examples can be given to
show that they are an important and sometimes even a key
42

43. factor in the development of diverse pathologic processes,
severe ones included [6].
Let us regard some other arguments speaking in favor of
our assumption. Let’s begin with the most principal one. A
number of embryonic cellular markers include substances of
protein nature with inherent antigenicity in an adult organism
in auto- and syngeneic systems. Therefore the embryonic
cells that happened to get into the adult organism will be
subject to the action of various effectors of the immune
system. And this impact will undoubtedly have certain
consequences for embryonic cells, that will be manifested if
not in their destruction but then in some serious functional
disorders, for instance, in differentiation disturbances. Thus
the immune reaction seems to be capable of acting as a
destabilizer of the situation. We don’t see any other
candidates for this role to play.
Let us word this hypothesis as the following postulate:
the factor, transforming embryonic ectopic grafts into
malignant ones in adult animals in syngeneic system,
represents an organism’s specific immune reaction. Let’s
consider further on, whether this postulate can be applicable
to the cases of carcinogenesis occurring under natural
conditions and can be modeled in the experiment, viz.: to
blastomas, induced by diverse carcinogenic impacts, as well
as to the tumors of viral origin and to spontaneous tumors.
Let us refer again to Ya. Ehrenpreis’ views on
carcinogenesis[17]. According to his ideas normal embryonic
cells are initially endowed with neoplastic potencies that are
realized in the form of malignant growth when embryonic
cells happen to get into non-embryonic conditions of their
existence; tumor cells are embryonic cells, devoid of the
posibility to participate in normal embryogenesis. As for
somatic cells, giving rise to tumor growth, they gain
embryonic properties and, consequently, also a potency to
neoplasia during the latent period of carcinogenesis. Since
embryonic properties, in this case, are transferred to cells,
not designed for embryogenesis, their further existence is
manifested as tumor growth.
If we consider somatic cells, embryonized under the
impact of carcinogenic factors, as the particular ectopic
embryonic grafts, then the above worded postulate may be
43

44. applicable, in fact, to all of the versions of carcinogenesis.
But in that case it seems to come into conflict with oncogene
theory, by which the only reason for cells neoplastic
transformation is derepression of oncogenes in them and no
other conditions for it are required. That is to say the event
of oncogenes’ derepression alone is already sufficient for
malignant transformation to take place.
To make these discrepancies agree, oncogenes’
functions should be analyzed in detail. Most of the scientists
believe that oncogenes play a very important part in an
organism (common to all species of living organisms), that of
regulating the cells’ growth and their differentiation [4].
Various oncogenes in placental animals are found to be
expressed freely in certain periods of their embryonic
development and it is quite natural that at this time they are
responsible for an organism’s cellular and tissue
characteristics, which we call embryonic ones. Oncogenes in
the process of an organism’s development are repressed.
But if they start functioning in an adult organism, then the
products of their activities appear to be immunologically
heterologous for the mature organism and a typical immune
reaction is developed in respect to them.
Taking into account all the above-stated, the mechanism
of malignant process origin is conceived by us as follows.
Under the impact of some external or internal factors in
organism’s cells there occurs derepression of
oncogenes. The direct result of activities of the latter is
oncoproteins and other biologically active compounds,
embryonic antigens included. In respect to them the
organism develops an immune reaction that deforms
the vital activity of cells containing activated oncogenes
to such an extent, that they lose their capacity for
differentiation and get transformed into malignant ones.
This vision of a sequence of events doesn’t deny the
oncogene theory, but on the contrary would rather
corroborate it as it eliminates the logical difficulty that
bewildered many specialists in the field of molecular biology,
including such an authority as G. Bishop, who believed that:
“What was found in the research, carried out by oncologists,
represented the first glimpse behind the veil that had hidden
a cancer mechanism for such a long time. What was
44

45. observed, was in one respect distressing since the chemical
mechanisms, that apparently “pushed cells off” onto the
pathway of malignant growth, did not differ at all from the
mechanisms operating in normal cells” (cited by [10]).
We will cite here one more statement. “The oncogene
concept, for all its advantages as compared to other
concepts of carcinogenesis, has at least one vulnerable link.
Scientists tried to understand how the cellular genes being
normal and apparently necessary for the vital activity, when
undergoing their minimum alteration (and sometimes,
maybe, without any but only as a result of their increase in
quantity), become detrimental for the cell and the organism
as a whole; what sort of genes are they, without which a cell,
on the one hand, is unable to exist and, on the other hand, is
incapable to resist their harmful action?” [10].
In accordance with the postulate proposed, the problem
of this contradiction can be solved in rather a simple way.
Actually, the chemical mechanisms (meant here are
oncogenes’ products and biochemical functions, brought
about by them) operate in a similar way both in tumor cells
and in normal embryo cells. No matter whether oncogenes
function in embryo cells or in an adult organism’s cells or
even in the cellular culture, the result will be identical. There
are no reasons to think that their activities’ products can
have different properties insofar as oncogenes’ nucleotide
matrix remains one and the same in all the cases shown.
The whole point is that the organism’s reaction to the
derepressed oncogenes’ products in the period of
embryogenesis and in the adult state is different. Therefore it
is not the chemical mechanisms as such that trigger tumor
process but the organism’s immune reaction “pushes” the
cell, embryonized as a result of oncogenes’ disinhibition, off
the normal pathway of differentiation.
In this connection it is necessary to consider a well
studied phenomenon – the phenomenon of
immunostimulation of tumor growth, playing an important
role in pathogenesis of malignant tumors. However, today it
hasn’t yet been given due attention either. This phenomenon
was identified when studying the immune reactions’ impact
upon the tumor process. Its manifestations were unnatural
and unclear. The reason for immunostimulation was first
45

46. believed to be some factor, not yet explored, that was even
termed as XYZ to emphasize its enigmatic nature. However
it was revealed very soon that this factor’s nature doesn’t
differ at all from the already known immune reactions.
The facts about the tumors’ immunostimulation have
been accumulated and finally an attempt has been made to
theoretically construe them. The tumor growth was believed
to be enhanced due to the blocking factors that impaired the
antitumor action of immune reactants and the tumor cells
started to reveal more freely their potential to rapid and
unlimited growth. But such a view was radically changed on
the boundary between 60ies-70ies, after R. Prehn started
working on this subject. At first the results of his
experimental works were published followed then by a
fundamental theoretical study carried out by him together
with M. Lappe [36]. This work showed that it was the direct
action of immune system reagents that led to the stimulation
of tumor growth. This kind of effect is induced by the
impaired immune reaction while the strong one is
responsible for the inhibition of tumor growth. Some time
later, a series of experimental and theoretical works by R.
Prehn and other researchers appeared to add arguments in
favor of the theory of tumor growth immunostimulation.
The opposite trends of the weak and strong immune
reactions’ action upon tumors isn’t something extraordinary.
It represents a well-known regularity consisting in that the
small doses of biologically active agents (even toxic ones)
stimulate the functions of biological systems while the large
ones – inhibit them. A great number of examples can be
given to confirm the universality of this principle. Therefore
the immune action on tumor cells isn’t an exception. The
action of the weak immune reaction upon a tumor will be that
of stimulation but with its power being increased the
stimulation terminates and the inhibition starts. The arrival
of this moment depends on the “stimulation width” (let’s thus
term it) of the immune action, i.e., on the range between the
power of immune reaction, when the stimulation just begins,
and its level when the stimulation is over. In pharmacology
corresponding to this notion is “therapeutic range” of drugs’
dosage.
46

47. Based upon observations of the tumor growth in diverse
versions of the experiment, R. Prehn has worded a postulate
by which every tumor in order to be stimulated requires the
immune reaction of such a magnitude and character, that is
peculiar to it alone [35].
Insofar as the specific immune reaction to the tumor
arises and develops gradually, its power will be first small –
the stimulation of tumor growth will be observed. Then,
despite the increase in this power, the blocking mechanisms
(aforementioned) start operating which will restrain this
augmentation. Integrated power of the immune reaction in
reality doesn’t ever reach magnitudes at which tumor
destruction starts. It remains always weak and acts as a
stimulator of tumor growth.
In the early 80-ies of the 20th century A. Ageenko and
co-authors performed a series of works, the results of which
are fundamentally important in terms of our knowledge of the
immune reaction role in pathogenesis of malignant tumor
growth. The authors put forward their own concept of the
role the immune system plays in pathogenesis of malignant
tumor growth, the underlying idea of which implies the
particular importance of embryonic antigens in the
processes of tumors’ origin and progression [1]. On the
surface of transformed cells at least two antigen groups
were shown to be expressed that mediate a different
qualitative result of immunologic interaction between tumors
and lymphocytes – immunocytolysis and immunostimulation.
The latter significantly exceeds immunocytolysisis in its
power and is realized in the line of stage-specific embryonic
antigens. The authors arrive at the opinion by which “it can’t
be excluded that immunostimulation is the mechanism that
triggers carcinogenesis and might afterwards play an
essential role in tumors’ progression”[1]. Thus these
investigations proved that an organism’s immune reaction to
the transformed cells plays an important role.
We consider it necessary to make here a short digression
in order to introduce an extraordinary essential specification.
We use the definition of “embryonic antigens” in relation to
those substances only, that being typical of embryos at the
early stage of ontogenesis, start to be expressed on
plasmatic membranes of transformed (i.e. embryonized)
47

48. cells and are immunogenic in autochthonous hosts and
syngeneic systems, and also activate T-lymphocytes. It is
important to emphasize this as the term “embryonic
antigens” is used widely enough in relation to a number of
substances that don’t generate any immune reaction in
hosts nor do they activate T-lymphocytes. These are, for
example, α-fetoprotein and carcinoembryonic antigen that
aren’t actually the specific markers of tumor process, but the
markers of proliferation alone. The importance of this
circumstance was emphasized by J. Coggin [22], who
indicated two antigens, in particular, which were expressed
in embryos and malignant tumors only and couldn’t be
identified in any other normal tissues by means of the most
high-sensitive technique. These are glycoproteins with
molecular masses of 44 and 220 kDa.
The fact, that such embryonic antigens have been
identified in all the tumors studied, without regard to the
source of their origin (ecto-, endo- or mesodermal) and a
species-specific belonging of the hosts (human, rodents)
[22-24,39] suggests the presence of universal features in
malignant tumors. If we take into account this circumstance
and an extraordinary limited quantity of these features, then,
finding the method to appropriately affect them, would make
it possible to work out a unified approach to malignant
tumors’ treatment.
Returning to the main subject of our study, we may state
that an organism’s specific immune reaction in respect
to malignant tumors is protective only in theory. In
reality, it is one of the initiating factors of neoplastic
process and its promoter.
Proceeding from the stated ideas on the mechanism of
neoplastic process formation and development, malignant
tumors should be interpreted as autoimmune pathology.
Richmond and Lisa Prehn in their article “Autoimmune
Nature of Cancer” [38] wrote the following: “Since the
immune reaction facilitates oncogenesis by MCA, MCA-
induced cancer can legitimately be termed an autoimmune
disease”. In this, the authors consider the MCA system isn’t
likely to be a unique one. Therefore they believe that when it
becomes known how to prevent autoimmune diseases, it will
be possible just as well to prevent not only the development
48

49. of MCA-induced cancer, but also the majority of malignant
tumors. A. Ageenko and V. Yerkhov single out an
autoimmune constituent of carcinogenesis too [1].
We, as distinguished from the many researchers
mentioned, believe that the immune system not just
stimulates the neoplastic growth, but we also substantiate
the statement, that it is a malignisative factor for cells,
expressing embryonic antigens; that it is the immune
system that plays a key role in the mechanism of
malignant process formation and development. The
significance of diverse carcinogenic effects comes thus to
their capability to derepress oncogenes at that time, when a
highly powerful system of non acceptance for their products
has been already formed, namely, the immune system. It
provides more grounds to speak of the malignant tumors as
a variety of autoimmune diseases.
Let’s now have a look at the other versions of
carcinogenesis and the experimental schemes to fight the
tumor growth in light of our postulate. Let’s dwell at first upon
the general theory of cancer by A. Cherezov [13] according
to which the reason for malignant tumors origin lies in the
tissue homeostasis’ disturbance. In correspondence to the
author’s ideas the structure of tissue homeostasis consists
of the various tissues’ stem (cambial) cells having a high
proliferation potential as well as all the signs of embryonality
(autocrine stimulation of mitoses, unrepressed oncogenes).
These cells ensure the renewal of the bulk of tissues’
specific cellular elements that gets diminished as a result of
natural deterioration and destruction. The strictly measured
functioning of stem cells, which corresponds to the scopes of
natural losses in the deteriorated differentiated cells, is
ensured by the mature cells’ capability to produce
substances, (chalones), having the property to inhibit the
cambial cells’ proliferative impulse. Under the action of
various carcinogenic substances there occurs
disarrangement of feedback mechanisms and the cells’
proliferation process begins to prevail. Many young cells that
have no time to differentiate are accumulated in tissue and
there occurs the tissue embryonization. As a result, the
tissue homeostasis structure and also then its function are
destroyed and a tumor originates. But it remains unclear
49

50. when the moment comes for the accumulated aggregate of
young embryonized cells to cease being the normal tissue
and to be transformed into a malignant one. We don’t find
any answer to this given by the author of the research. If
viewed from the standpoint of the postulate under
consideration we will see the answer to it lying right on the
surface. The embryonization process of proliferating tissue
won’t go beyond the frame of the normal phenomenon until
a certain amount of stem cells that are being reproduced
and express embryonic antigens, reaches the critical mass,
capable of becoming an object of reception by an organism’s
immune system.
Immunologic recognition is known to take place only in
that case when the cells, bearing heterologous antigens,
make up a group of no less than 105 units [5], while the
tissular conditions don’t impede it. The immune reaction that
follows, imparts a malignant phenotype to the cells. It is this
very moment that is crucial in the origin of neoplasms in all
the versions of tissue homeostasis’ disturbances.
Proceeding on with the discussion of the postulate, let us
refer to the classic experiments conducted by B. Mintz to
obtain allophenic chimeras [30]. The allophenic chimerism of
healthy and full-value animals emerged in these experiments
as a result of inoculating into the blastocyst of mice of one
line the teratocarcinoma cells, derived from the animals of
another line which had clear-cut phenotype distinctions from
the first one in the form of black fur coloring as well as some
biochemical markers. In the mice produced from the
blastocyst with the inoculated malignant tumor cells, the
tissues and organs (right up to germinal ones) were built of
the maternal organism cells and of the inoculated malignant
tumor cells that lost their malignant phenotype and were
involved in normal embryogenesis.
Teratocarcinomas are known to be obtained by
inoculating the embryonic cells of an embryo of pre-
implantation stages of its development into the so called
immunologically preferential sites (anterior chamber of the
eye, testes, subcapsular space of the kidney and others),
wherein there are conditions of relative immunological
tolerance. Manifestations of the immune reaction can be
observed in these sites too though in an impaired form [15].
50

51. This immune reaction appears to be sufficient to impart
malignant phenotype features to the inoculated embryo
cells. Further on, these cells (being already malignant ones)
are passaged on mice in the form of ascitic teratocarcinoma,
i.e., they are always placed in non-embryonic conditions
where they are recognized by the immune system and are
perceived by it as foreign ones. Before being used by B.
Mintz in her experiments such teratocarcinoma cells have
previously gone through 200 passages in the form of a
malignant phenotype. But once they happened to get under
the conditions of a developing embryo they immediately lost
their malignancy. This suggests the fact that a malignancy
sign in this case is not associated with the stable genic
aberrations, but is shaped by the environmental conditions
where the main point is the presence or absence of an
organism’s immune reaction. Consequently, the embryo
cells being exposed to an organism’s immune reaction are
transformed into malignant ones, while the malignant cells,
when getting under the conditions of normal embryogenesis
(with no immune reaction present), become normal and
capable of being involved into the normal form-building
process.
In the midst of the 70-ies of the 20th century in the
Institute for Oncology Problems Acad. Sci. UkrSSR,
investigations were carried out, the results of which were
consonant with the experimental data, described by B.
Mintz. When cultivating in diffusion chambers under the
conditions of a healthy animals’ organism the Shwets
erythromyelosis cells of rats, featured by non-differentiated
blast elements of myeloid and erythroid series, M.
Baranovsky [3] observed their differentiation, that over 13
days’ period of explantation in the red branch of
hemopoiesis was completed with the appearance of nuclear
baso-, polychromato- and oxyphile erythroblasts, but in
myeloid- monocytic branch of hemopoiesis – with the
appearance of final functional (phagocyting macrophages)
and morphologic (segmented granulocytes) forms. Thus,
suffice was it to place leukemic cells, by means of a diffusion
chamber under the conditions of isolation from the
organism’s immune system (it being represented by its
cellular elements only) that their differentiation started to
51

52. occur. However the results of these experiments have never
been analyzed in this aspect.
It will be expedient to mention here the findings of several
studies that obtained evidences to the effect that malignant
tumor cells, being inoculated into embryo, don’t give rise to
neoplastic process. So, taking into consideration a generally
known fact of the absence of spontaneous tumors in higher
animals at early stages of embryonic development, A.
Savinska [8] cleared up the question as to whether
implanted tumors would grow and develop in embryos in
different periods of their intrauterine development. Sarcoma
cells’ suspension N16 in physiological solution or Ringer
solution with carmine, added for control, was injected
through the uterus wall into rats’ embryos. 282 rats (2204
embryos) were operated. 172 embryos (36 rats) were
brought to the end of the experiment. Sarcoma, inoculated
into embryos at the last third of their intrauterine
development, grew and developed both in newborn rats and
in female-mothers. When inoculating sarcoma to embryos at
the first two thirds of their intrauterine development, tumors
were developed in females only. The newborn little rats
remained entirely healthy. The tumor failed to have taken on
in anybody out of 19 embryos at this period of intrauterine
development. Origination of tumors in all the cases of
pregnant females after inoculating the tumor material into
embryos suggests that the material was living and virulent.
A.Savinska’s experiments were repeated by M. Whisson [42]
with implanted Iosid sarcoma of rats – no tumors emerged in
anyone of 72 embryos that had undergone operation.
Similar experiments were also conducted by B. Tokin and
M. Aizupet [12]. Jensen sarcoma cells’ emulsion was
injected into rats’ embryos (from 9 to 12 days of pregnancy).
Little rats at the age of one week and adult animals served
for control. Out of 172 fetuses born who were inoculated with
tumor suspension in the period of their embryonic
development, only 11 (6,4%) developed tumors. In control
animals tumors have been taken on in 80% of cases.
Tumors’ non-inoculability in embryos of the first two thirds
of pregnancy in experiments, conducted by A. Savinska, M.
Whisson and B. Tokin, can be easily explained from the
standpoint of our postulate, that is, by undeveloped immune
52

53. system in embryos and, therefore, by the absence of its
action upon tumor cells.
The degree of success of malignant tumors implantation
into embryos of both young and adult animals coincides in
terms with the stages of formation of their immune system.
Unfortunately, the state of the inoculated tumor material was
not studied further on in the above experiments.
Thus the main stages of carcinogenesis, in our opinion,
may be considered as follows:
1. The initial material for malignant neoplasms is cells,
expressing embryonic antigens.
2. Such cells might emerge in an organism either as a
result of oncogenes’ disinhibition under the impact of
various carcinogenic factors or as a consequence of
tissue homeostasis’ disturbances, during which the
disturbance in balance between cells’ proliferation and
differentiation occurs with the predominance of the first
one. In case of a long-term character of proliferation
process and increase in the imbalance mentioned, there
may be a local accumulation of a significant amount of
young (stem, committed) cells having embryonic
characteristics.
3. Such cells, according to the existing views [5], are
exposed to the effectors of an organism’s natural
resistance system, capable of recognizing small amounts
of aberrant cells, right up to the isolated ones. A
considerable number of these cells may be destroyed but
some amount of them is preserved evading cytolysis.
4. The next stage in the development of tumor process is
the formation of a cellular conglomerate out of the cells,
having survived after the “attack” of the organism’s
natural resistance system, of no less than 105 cells — a
critical mass that can be recognized by the receptors of a
specific immune reacting system.
5. After the immune reception of antigenic determinants of
accumulated cells’ has occurred the stage of formation of
an organism’s immune reaction to those determinants its
action upon the cells which finally calls forth their
malignant transformation.
53

54. 6. Since this moment an antagonistic interaction originates
between the organism and tumor cells, that is manifested
in the form of tumor disease with all the variety of
symptoms, during which progressive tumor growth is
continuously supported by the immune stimuli.
Malignancy of the neoplastic process flow depends, on
one hand, on how strong are the tumor cells’ potencies for
the progressive growth (as a rule, the less differentiated are
the cells, the higher are these potencies); on the other hand
it depends on how the character and the power of an
organism’s immune reaction in respect to the tumor
correspond to that level of this reaction at which its strongest
tumor-stimulating effect is observed.
Summing up all the above-stated we come to the
following conclusion: irrespective of the nature and kind
of carcinogenic factors as well as the circumstances of
their action, a cellular conglomerate expressing
embryonic antigens is shaped in an organism, sufficient
in quantity for its reception by the organism’s immune
system. It is the impact of the immune system effectors
upon this conglomerate that is responsible for its
gaining the properties of a malignant tumor and for a
further promotion of its growth.
Thus, the specific organism’s immune reaction is unable
to realize that kind of action, on which so much hope was
once set. Under the natural conditions, it realizes just the
opposite function, bringing about the formation of a
malignant tumor process and promoting its development.
Contemporary oncology has two alternative directions to
solve the problem of malignant tumor growth. Both the first
and the second ones are science-based and have a
perspective for achieving favorable results. The main idea of
the first one consists in striving to radically eliminate tumor
cells wherever they may be [7]. Nowadays tremendous
intellectual and material resources are turned to the
development of this direction. Another direction is based on
the data, according to which malignant tumor cells retain
their potential capacity for differentiation [11, 15, 33]; it
provides for the possibility to create conditions for
retransformation of malignant cells into normal ones (it’s in
an ideal case) or to achieve partial rise in the grade of tumor
54

55. cells’ differentiation, resulting in their malignancy decrease
[14]. Advantages and attractiveness of such a direction are
indisputable. It is this second pathway where we see the
prospects for our ideas to be developed.
We believe that the transformed cells’ capacity for
differentiation may be realized, on condition, that the
factor impeding it, i.e., an organism’s immune reaction
to tumor antigens, the embryonic ones in particular, has
been eliminated.
Analyzing the problem of malignant tumor growth under
some other aspect, M.G. Baramiya arrived at the similar
conclusion: to overcome the disintegrated (i.e. malignant)
growth it’s necessary to induce and maintain in a tumor-host
a status of absolute immunologic unresponsiveness to the
transformed phenotype [2].
We regard all the above-stated as substantiation of a
fundamentally novel immunological approach to malignant
tumors’ treatment, and the previous experimental findings
corroborate the productivity of this idea [16].
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59. Discussion
The results of the experimental and preceding clinical
studies described may be regarded as a confirmation of the
productivity of our hypothesis’, main postulate according to
which the way to fight malignant tumor process lies via
elimination in a tumor-host of the immune reaction to tumor
antigens, but in that case only if to consider that the injection
of placenta extract into an organism of patients suffering
from malignant tumors induces in it immunologic tolerance to
these antigens. The findings of other researchers give
ground to consider it so.
In 1980 G.Chaouat and colleagues [1] reported that using
the water placenta extract of mice at the second week of
pregnancy they induced in these animals a state of
immunologic tolerance to alloantigens which was manifested
by the allograft having been taken on in them.
In this, two conditions were determined under which this
phenomenon could be realized: a recipient of the graft must
have a previous contact with alloantigen while the allograft
cells must be injected into the recipient together with
placental extract or in a very close vicinity to each other.
In 1983 the results of studies by T.Mekori and R.Kinsky
were published [8], who keeping to the fundamental scheme
of experiments conducted by G.Chaouat induced in mice the
tolerance to xenoantigens (erythrocytes of sheep and
pigeons). Placenta extract was prepared according to the
methods described by G.Chaouat. The researchers also
confirmed the necessity for the animals to have a previous
contact with antigens to which the tolerance is to be induced
and a previous contact of placental extract with these
antigens. The placenta extract without the previous
interaction with the antigen caused no suppressive effect.
The induced tolerance had a specific character which was
demonstrated by modulating the crossed reactions with
sheep’s and pigeons’ erythrocytes. The following scheme for
the immunosuppressive action of placental factor can be
drawn out. It is being produced in an inactive form, gaining
its potency and a specific character on having a contact with
antigen. Being activated it manifests its immunosuppressive
effect under the only condition, that of getting sensitized by
59