Note : Les descriptions sont présentées dans la langue officielle dans laquelle elles ont été soumises.
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FIELD OF THE Il\IVENTlON
The present invention refers to the treatment of cancer and,
more particularly, it is related to a composition and a method of
treating cancer, useful for involuting a carcinoma in any stage of
evolution thereof.
BACKGROUND OF THE INVENTION
It has been fully recognized in recent years that cancer can
start in just one of the body's billions of cells, triggered by a stray of
radiation, a trace of toxic cheniical, a virus or a random error in the
10 transcription of the cell's genetic message. Once the genetic message
of the cell has been altered by any external or internal influence, the
cell starts to divide to form other abnormal cells, under a process
that violates normal genetic restraints, The immune system of-the
body, on the other hand, which is normally alert to the presence of
any type of alien cells, falls to respond properly and its defense units
refrain from attacking and destroying the intruder cells. Unlike healthy
cells, which stop reproducing after repairing damage or contributing to
normal growth, the aberrant cells (cancerous cells) have no boundary in
connection with the d-ivision properties and continue to proliferate widly,
20 forming a growing mass or tumor that expands into healthy tissue and
competes with normal cells for nutrition. ~Iso, the malevotent cells
may be transferred into the bloodstream or the Iymphatic system which
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carries them all over the body thu~s creating what is termed
metastasis .
While workers in the art usually have the strong feeling that
cancer could be stopped if the altered genetic message of the cell could
be restored, no means have been deviced up to the present date to effect
such restoration. Therefore, the customary and what are considered
the best treatments for cancer is to have the liFes of the patients
.
prolonged for a few years by one or a combination of three kinds of
often unpleasant, debilitating and sometimes disfiguring treatment,
10 namely, surgery, radiation and chemotherapy. Regardless of the
existence of these types of treatments commonly applied to cancerous
patients, two-thirds of all cancer victims eventually die of the disease.
In more recent years some;further and more remarkable
developments have heen made thn~ugh the production of a relatively
efficient vaccine for treating human cancer in breast, lungs, ovaries,
cervix and gastrointestinal tract, said vaccine being prepared from a
tumor material derived from~at least one or more human cancers
developing in a specific predetermined organ and admixing several
cf said materials and treatlng the same to produce vaccines which
20 are relatively effective against the development of cancer in the above
mentioned organs of the~ human body. However, the percentage of
relief obtained by the patients is relatively low and the production of
said vaccine is expensive and painstaking, whereby this may be
considered as most as a partial cure and as one of the best efforts
made in the recent times towards the alleviation of this affliction.
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One other most hopeful discovery made in recent years is
interferon (IF) which seems to be a protein contained and produced
in minute amount by living cells, but while the alleviation of the
disease through the use of interferon seems to be very promising,
the obstacles encountered in the development of production of said
substance are almost impossible to overcome, because interferon
is a very specific substance which is produced by animals and which
acts only in animals of the same species and is not oF general applica-
tion. In other words, interferon produced by human cells is only effective
10 a~ainst cancer of humans, whereas interferon produced by other types ~f
mammals or vertebrate animals are specific only in the same species
of the animals whose cells produce said interferon, whereby there is
no possibility of obtaining animal interferon to be used in humans or
viceversa . Therefore, the only manner of having an interferon which
may be active against human cancer is to obtain said interferon from
human celis and this, obviously, represents an almost unbeatable
obstacle in view of the tremendously high cost and the exaggerately
small amounts in which interferon may be produced, whereby this
technique may not be the best solution for cancer disease which, only
20 in the United States of America kills around half a million people every
yea r .
Therefore, regardless of the tremendous efforts and expenses
made by worldwide institutions endeavored in the research of cancer
diseaseJ up to the present date no reasorable cure has been developed
which may be regarded as specific or at least reasonabLy effective
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against many kinds of cancer. Therefore, the only way of attacking
cancer and this only in certain instances such as in melanoma and
certain adenocarcinomas of the mammal gland, is to discover the
car,cer in an early stage of development and to apply surgery and
thereafter radiation and chemotherapy to try to cure the disease,
w~th a low percentage of satisfactory cases.
BF~IEF SUMMARY OF THE INVENTION
Having in mind the defects of the prior types of cure for
cancer disease, it is an object to the present invention to provide
10 a composition for the treatment of cancer which is useful for most
types of cancer and which may be effective in any stage of development
of the disease.
It is another object of the present invention to provide a
composition for the treatment of cancer, which will directly act
upon the genetic message of the cells in order to inhibit the wide
reproduction abilities of can~erous cells.
One other and more particular object of the present invention
is to provide a composition for the treatment of cancer which is derived
from an abundant starting material available in vast amounts to serve
20 as a radical cure for cancer.
It is another object of the present invention to provide a
method oF treating cancer which may be effective for curing the
disease in a large percentage of the cases in any stage of development
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of said disease.
The foregoing object and others ancillary thereto are
preferably accomplished as follows:
According to a preferred embodiment of the present
invention, cancer is cured at any stage of development of the disease
by the method which comprises administering to the patient through
the oral route, a suitable daily dosage~ during a period of time of
about from 45 to 60 days, of a composition comprising a colloidal
or semi-colloidal suspension of DNiA-repressor proteins derived
from a fresh mammal nerve tissue, particularly brain tissue,
alternated with the parenteral administration of immunoglobulin
(gama -globulin) .
The novel features that are considered characteristics of
the present invention ar set forth with particularity in the appended
claims. The invention itself, however, both as to its organization
and its method of operation, together with certain theoretical considera-
tions to which applicant does not wish to be bound, as well as additioral
objects and advantages thereof, will best be understood from the following
detailed description of certain specific embodiments which are merely
given as illustrative but not as limitative of the present invention.
DETAILED DESCRIPTION
,
In recent years it has been learned that a fundamental property
of living cells is their ability to turn their genes on and off in response
7~
to extracellular signals. In the human body, for example, every
cell (with the exception of a few cell types such as the red blood
cell) has the same set of genes, yet in the course of embryonic
development cells take on different shapes and functions as their
genes are selectively switched on and off.
Through the study of gene regulation in bacteria and viruses
it has been learned in recent years that a fundamental mechanism of
gene control depends on the interaction 0lc protein molecules with
specific regions on the long-chain molecule of DNA. As a result of
lO this interaction genes are switched on or off. In the best-understood
instances genes are switched off by controlling molecules named
repressors. The existence o~ repressors was first hypothesized
in 1960 by Francois Jacob and Jacques Monod of the Pasteur Institute
in Paris. Sever years later Walter Gilbert (in collaboration with
Benno Muller-Hill and, Ptashne, working independently at Harvard
University, succeeded in isolating repressors from bacteria (see
"Genetic Repressors," by Mark Ptashne and Walter Gilbert;
ScientiFic American, June 1970). Later it was shown that repressors
could bind tightly and specifically to sites on DNA called operators and
20 that in so doing they could prevent genes adjacent to the operators from
being transcrited and translated into proteins.
In man, as in bacteria, a gene can be deFined as a sequence
of bases along a DNA molecule. The DNA molecule consists of two
long chains of nucleotides wound in a double helix and linked to each
other by hydrogen bonds. Each nucleotide consists of a deoxyribose
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sugar, a phosphate group and one of four nitrogenous bases: adenine,
guanine, thymine or cytosine (abbreviated A, G, T and C). The sugar
and phosphate groups form the backbone of each chain; the bases
extend toward the central axis of the double helix and pair with the
bases extending from the other chain. The sequences of bases along
the chains are complementary: A always pairs with T and G always
pairs with C. The information content of DNA is specified by the
sequence of bases . A typical gene corsis~s of roughly 1,000 base pairs.
l~he translation from gene to protein begins with the enzyme
10 RNA polymerase, which copies the base sequence into a complementary
sequence on the linear molecule of "messenger" RNA. The intracellular
translating machines called ribosomes attach themselves to the messenger
RNA and translate its base sequence into a sequence of amino acids,
which are linked to form a protein molecule.
It is clear that the translation of a gene into a protein molecule
might conceivably be repressed or blocked at any one of several stages
along the complex gene. Recent studies have determined that repression
takes place directly at the DNA molecule, so that the genetic information
is not transcribed into "messenger'1 RNA unless the repressor is
20 inactivated.
Repressors are generally small sized acid proteins generated
by a so called regulator gene in the DNA, which attach themselves to
the promoter region of the operator of a gene thus preventing the RNA
polymerase to attach itself to said promoter region and assemble the
messenger RNA.
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Once having reviewed the basic mechanism of repression
of the transcription of the gene, and while applicant does not wish
to be bound to any theoretical explanation of the manner of acting of
the composition of the present invention, it is to be stated that it is
believed that cancer is the chemical alteration of the order of the
nucleotides adenine, guanine, thymine and cytosine constituting the
gene which regulates cellular duplication and codifies the synthesis
of a specific protein which works as a repressor of an operator gene.
This alteration, caused by physical, chemical or biological agents in
10 a cell, transmits hereditarily this transformation to the daughter
cells which cannot appropriately synthesize the repressor, thereby
generating the wide reproduction of the cells and forming the abnormal
tissue masses (primary tumors) which may; disseminate through
metatasis to other organs.
In a normal cell the specific repressor protein adheres to
the DNA, as mentioned above, In the promoter region of a gene operator
and inhibits transcription of the structural genes that control the
development and the synthesls of RNA.
On the other rand, there are certain specific receptor proteins
20 located at the cythoplasm of the cell3 adhered to the membrane and which
are sensitive to the intercellular contact and record the empty spaces of
a tissue, probably through electromagnetic changes, thereby inducing
cellular duplication when they migrate towards the nucleus of the cell
and adhere to the DNA, particularly to the regulator gene and avoid
synthesis of the repressor protein which control s the population of
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cells in a living organism.
It is believed that the cancerous cell contains an altered
repressor protein which does not work or is merely deprived of
said protein, depending on the change which has been caused in the
regulator gene and, therefore, said cell is always in a condition of
continuous transcription of the structural genes, thus resulting in
an indefinite duplication.
The susceptibility of a cell towards cancer very much
depends on an increase in the permeability of its membrane which
permits physical, chemical or biological cancer developing agents
to enter into contact with its Dl~ . Thus, some hormones act by
affecting the speed oF enzymatic catalysis or by altering the permeability
of the cellular membrane and this circumstance renders those tissues
which are subject to a continuous hormoral stimulus more prone to
cancer, for instance, the mammarian gland and the uterus.
Lack of nutrition may be another circumstance causing an
ircrease in the permeability of the cellular membrane, as well as
the depression of the immuno competence, which are factors facilitating
the action of oncogenic viruses.
It has also been ascertained that the cytoplasm of every cell
in a living tissue, contains a multiplicity of mole cules of a so called
receptor protein. This protein, probably due to electromagnetic or
electrochemical changes, senses the empty spaces of the neighboring
tissue where cells are needed and, upon doing so, the receptor protein
migrates toward the nucleus of the cell, attaching to the regulator gene
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of the DNA which therefore will no longer produce the repressor
protein to block the promoter region of the operator gene. Therefore,
said promoter region will cease to be repressed and will trigger the
operator gene to start the formation of messenger RNA and the
reproduction of the cell to fill the empty spaces'of the tissue. The
action will be reversed when the receptor proteir,s sense no empty
space once it is filled with new cells. . This may be the mechanism
by which a predetermined cell reproduces itself only when needed
and remains dormant in this respect when reproduction is not needed
` 10 by the living organism.
The increase in the permeability of the membrane of a cell,
may permit external oncogenic agents, mainly viral DNA, to permeate
said membrane and migrate to the nucleus of the cell, attaching itself
to the regulator gene permanently, whereby said regulator gene will no
longer produce the appropriate repressor protein. Therefore, the
continuous reproduction of the cell will be triggered by the absence
of the repressor protein and the cell will become malignant.
It is clear, therefore, that if a repressor protein contained
in a tissue is administered to a patient, said repressor protein will
substitute the repressor protein no longer being produced by the
malignant cell, and will act directly on the promoter region of the
operator gene to prevent the latter to trigger the continuous reproduction
of said cell.
It has been found that all nervous tissue of mammals, in being
cells that never reproduce during the life time of the individual, contain
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high amounts of these repressor proteins, whereby when administered
to a patient through the gastrointestinal tract, are transported through
the Iymphatic and blood systems to the cells affected by cancer. As
these cells have the permeability of their membranes considerably
- increased, the administered repressor protein will penetrate said
membranes and attach to the promoter region of the operator gene of
the DNA of said cells, acting as repressor mc:lecules instead of the
normal repressor molecules that are not being produced by the regulator
gene of the malignant cell.
That is the reason why a composition of matter containing a
colloidal or semi-colloidal suspension of DNA repressor proteins
derived from a fresh mammal nerve tissue and particularly from
brain tissue, has been found to be extremely active in repressing and
preventing reproduction of cancerous cells and ultimately produce the
involution and disappearance of the tumors originally formed by said
cells,
This type of repressor proteins provided by the composition
of the present invention not only act within the tumor itself but also
act through the chyliferous vessels and the blood vessels in order to
20 attack metastasized cells, thereby also inhibiting metastasis of cancer
in a patient affected by said ailment,
The composition of nervous tissue in accordance with the
present invention may be prepared by immersing a nervous fresh
- animal tissue obtained from a recently slaughtered mammal into an
aqueous solution of iodine (1:2500) during a period of time of from
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about 1 to 3 minutes, in order to sterilize said tissue and to avoid
the participation of any living bacteria or other germs. The fresh
tissue is removed from the iodine solution and is thoroughly washed
with distilled water in order to wash the absorbed iodine and thereafter
the said tissue is comminuted~ for instance, in a blendor, during a
period of 1 minute or less, in order to form a colloidal or semi-colloidal
mass which is preserved under freeze conditions, because the pharmaco-
logical action very much depends on the integrity of the proteins that it
contains, which proteins are sensitive to high temperatures.
In order to administer the composition of matter of the instant
application, the same is thawn and applied orally to the patient suffering
of cancer, p^referably at dosages of from CJ.5 to 10 mg/mg of tumoral
tissue determined in the patient and for a period of time of from about 45
to 60 days, whereafter a remarkable involution and firal cure of the
disease is observed in a large proportion of the cases.
The following examples will illustrate the effectiveness of the
composition of the present invention as applied by the method of treating
cancer disease described aboveO
EX~M PL E
A group of 20 hamsters was injected with cancerous cells to
induce an adenocarcinoma in the mammarian gland and the cancer was
allowed to develop to an intermediate stage. When the adenocarcinoma
was fully developed in all of the twenty selected hamsters, a group of
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ten of said hamsters was treated with a composition comprising
finely divided and sterilized brain tissue of a recently slaughtered
bovine animal, in dosages of 1 ml each 24 hours during 30 days,
equivalent to a dosis of about 5 mg/kg of hamster per day. No
immuno-globulin~m~a~lobulin) was used in the treatment of
the hamsters
The group of ten hamsters selected for treatment was
closely observed and by the end of the 15th day as of initiating the
treatment, the tumoral tissues began to decrease and involute,
10 whereas after 30 days of treatment a complete disappearance of the
adenocarcinoma was accomplished, and the weight of the animals
increased 7%, said hamsters being fully recovered by the end of
the 30th day.
The group of ten hamsters which were not treated in
accordance with the above, were also observed. ~11 of them,
without a single exception, showed a considerable increase in the
tumoral volumes, loss of living characteristics and loss of weight
of up to about 20%. All of said hamsters died within the next 90
days .
20 EXAMPLE 2
The procedure of Example 1 was repeated~ but using a
brain tissue obtained from a recently slaughtered equine animal.
The results proved to be the same as in Example 1.
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EXAMPLE 3
A group of 30 voluntary human patients suffering of fully
developed and metastasized cancer in different organs was treated
with a composition prepared as follows: A portion of brain tissue
obtained from a recently slaughtered bovine animal (lamb) was infused
in a solution of iodine (1:2500) during two minutes, the disinfected tissue
was thoroughly washed with distilled water and thereafter it was
comminuted in a waring blendor during a period of 1 minute to reduce
the tissue to the consistency of a heavy syrup.
The thirty selected patients were distributed as follows:
twelve of said patients had received one chemotherapy treatment by
the administration of vincristine, adreamicine and cyclophosphamide;
fifteen other patients had been already treated two or three times with
chemotherapy and several times with radiotherapy, and a further group
of three patents was already treated by a multiplicity of chemotherapy
sessions and radiotherapy and had a very advanced cancer attacking
vital organs, such as liver, lungs, kidney and intestine.
All the thir~y patients were treated by administering an
approximate daily dosage of 1 mg/mg of tumoral tissue (determined
for each oatient) of the above composition, and were also administered
w ith either human immuno-giobulin (j3~m~a-globulin) at a dosis of l ml
each 72 hours parenterally during three weeks, or immunoglobulin
(samma-globulin) obtained from horse in the form of suppositories
of 10 mg, by administering one suppository ever~ 24 hours during
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12 days, as a means to protect the patients against viral reinfections.
Also, all the patients were administered calcium phosphate
pills of 400 mg each, three times per day during the period of
administration of the gamma-globulin.
The results obtained with the above treatment are as follows:
The twelve patients that had received only one single chemotherapy
treatment had a perfect evolution, with complete dissapearance of the
tumoral tissues and, after one year of control as of finalization of the
treatment, the tumoral tissue indicators, namely, lactic dehydrogenase
lO and alkaline phosphatase, came down to normal values of about 193
International Units (IU) for the lactic dehydrogenase and of about 72
IU for the alkaline phosphatase. None of said twelve patients have
shown any tendency towards an increase in the above indicators during
the one year of control closely kept upon them.
The fifteen patients that had suffered already two or three
treatments by chemotherapy and several radiotherapy treatments,
did not respond satisfactorily to the treatment and, while in some
cases the carcinomas were reduced in volume, the treatment did not -
relieve them fully from the disease. These patients had to continue
20 with chemotherapy and radiotherapy treatments after the above mentioned
treatment, without any satisfactory resul-ts.
The three patients who had received many chemotherapy
treatments and radiotherapy treatments and that had a cancer affecting
vital organs, all of them died despite of the treatment of the present
invention .
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The above shows that the treatment is more effective when
the cancer has not been treated by chemotherapy or radiotherapy)
regardless of the stage of development (under reasonable limits) and
metastasis invotved, and that the said chemotherapy treatments, by
reducing the immunological response of the patients, renders them more
prone to viral infections, and it is believed that the viral infections have
much influence in the development of cancer by modification of the genetic
message of the cells of the patients. Out of the thirty cases, only
twelve were satisfactorily treated and are fully alleviated from the
lO disease, which means that the treatment carried out as described in
this example has proven to be effective in at least 40% of the cases,
by using the brain tissue of a bovine animal.
EXAMPLE 4
Another group of twenty voluntary patients, 10 of which had not
received more than one chemotherapy treatment and no radiotherapy
treatment at all, and 10 of which had received several such treatments
(chemotherapy and radiotherapy) were also treated by using the same
type of treatment described in example 3- above, but by preparing the
composition of the present invention using brain tissue obtained from
20 primate animals, particularly American monkey, with the result that
nineteen out of the twenty cases were completely alleviated from the
disease and the controls exerted upon said patients during one year as of
treatment have kept the tumoral tissue indicators within normal levels,
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which means that said patients have been fully alleviated from cancer
disease and only one had to undergo a repeated treatment because the
involution of the tumoral tissues, while satisfactory when the first
treatment was applied, was not sufficient to completely inhibit all the
cancerous cells and perhaps the viral infections affecting said patient
after the treatment caused a reinstatement of the tumoral growth,
whereby a second treatment identical with the above described
treatment was applied to him. Said patient is under observation
up to the present time, also with satisfactory but still uncertain
lO results.
Thus, the treatment carried out in accordance with this
example showed 95yO favorable results.
The above examples give some hints as to the effectiveness
of the composition and treatment in accordance with the present invention,
in the sense that, when treating hamsters with bovine or equine brain
tissue, 100% success was obtained, whereas when treating humans with
certain bovine brain tissues, together wlth gamma-globulin and calcium
phosphate treatments, only 40% of the cases was considered to be entirely
satisfactory. ~bwever, the proportion of alleviation was increased
20 considerably to about 95%, when using brain tissue of primates, which
are animals closer to the human race in the zoological scale.
The above might mean thatg if certain legal provisions and
ethical barriers are overcome, perhaps the use of human brain tissue
would achieve a 100% success, but no experiments could be made with
human brain tissue particularly if it is considered that the oral ingestion
thereof would be ethically rejected, and it would be necessary to effect
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Iyophilization of said tissues in order to administer thern perenterally.
~ lowever, it is a fact that the closer the animal is to the
human race, the more effective is the action of the brain tissues of
' said animals in alleviating the development of cancer.
The above, obviously, may be due to the fact that the repressor
proteins contained in the brain tissue of a species of animals close to
the human race, may be more similar to the human repressors that
are affected when cancerous cells are developed, thus acting as a perfect
substitute for said lost or altered repressor proteins, which are no
lO longer being produced by canc0rous cells.
It may be seen from the above that for the first time a simple
treatment for cancer disease has been developed and a very effective
composition of matter has also been provided which may be regarded
as very promising in the cure of cancer disease, giving a percentage
of successful cases which is mugh higher than those produced by any
treatment of the prior art that has come to the attention of applicant.
Although certain specific embodiments of the present invention
have t~een shown and described above, it is to be understood that many
modlfications thereof are possible. The present invention, therefore,
20 is not to be restricted except insofar as is necessitated by the prior art
and by the spirit of the appended claims.
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