ANALYSIS OF THE MECHANISMS OF ACTION

ANALYSIS OF THE MECHANISMS OF ACTION OF ENERCEL® THERAPEUTICS

By Ernesto Crescenti, M.D., et al.
Completed July, 1991- Translated from Spanish 1992

PREFACE

Several years ago, the author, Cesar Bertacchini, M.D., and others decided to join together in promoting and maintaining the research by Argentine investigators regarding aspects which were believed necessary in order to reach definitive success in the worldwide fight against cancer. The decision was to bring the main character of this struggle into the picture. This, of course, is the patient who has cancer.

Joining forces, through the Research Center, results were made available to the scientific and medical teams of more than fifteen years of phytological investigations. In this study, every plant, every botanical specimen gave specific answers. These answers led to the wisdom and the need to return to “primitive” or natural medicine, keeping the patient in mind at all times.

The physicians who were trained at the Center, made great progress during more than five years in the research and application of homeopathic magistral formulas, comparable to those in the World Homeopathic Pharmacopoeia, which above all would be found to be effective if the following were simply observed:

a) That persons from any country such as ours who have ignored or neglected the advice of the Advisory Committee of the World Health Organization, which met in Geneva on November, 1962, to establish a permanent national program to fight against cancer, countries in which even smoking is promoted by mass communication media which are in the hands of the government, have no incentive to fight against cancer. They are just accustomed to living with cancer and dying of cancer.

b) That we are completely convinced that immunologic factors are involved in the resistance to cancer and in the destruction of neoplastic cells. The cancer patient must be taken into account, and he must be made aware of this principle since he is the main character in this fight.

c) That the WHO reminds us that in 1987 “half the diagnosed cancer cases and two thirds of the deaths due to that cause occurred in developed countries.” Given this, we in developing countries do not stand even a chance of becoming developed. Cancer in those developing countries is more prevalent and takes a greater tool. The struggle and the challenge are in these countries, and we must begin now.

d) That no curative process can begin if there is no hope. Hope can be found only if the patient believes that something or somebody can help him get well. Dr. Bernie S. Siegel reminds us that, “hope is good medicine.”

That is why today, it is a pleasure to preface this humble proposition made to the international scientific community, which proposes a restatement of the problem and asks us to ponder about the two main characters in the final success in the fight against cancer without which the battle will have no success and every proposition that does not take them into account is bound to fail: THE PATIENT and THE PHYSICIAN. It also proposes a youthful attitude of rebellion which is good for science: instead of living with evil we must destroy it. We should even imprint that rebelliousness in the genetic makeup of every human being. That is where ultimately our success will come from.

Buenos Aires, Argentina
July, 1991 Cesar Bertacchini, M.D.

ANALYSIS OF THE MECHANISMS OF ACTION OF ENERCEL® THERAPEUTICS
ENERCEL®
: An Unconventional Therapeutic Method

Faced with the need to present to the scientific community for its judgment the effectiveness and possible mechanisms of an unconventional therapeutic method, the first thing we must face and defeat is skepticism. To help us do that, let us remember what Professor Gregorio Araoz Alfaro said in 1927: “Nothing is sufficient. He who believes he has the definitive truth lies tranquil and secure in his error.”

On the other hand, we need to make it very clear from the beginning that our method meets what we believe to be the main rule in medical practice: “Primum non nocere*” which has been demonstrated in our experience with animals and in thousands of patients who have received the treatment in the last few years. This has occurred although we have used intramuscular or intravenous administration daily; with an almost nonexistent incidence of abscesses or complications, less than usually occurs with such administrations.

Called “Homeopathics,” a name given substances used in our medication because they are not measurable or undetectable by methods which science has at present, we will try to apply a rigorous semantic and scientific approach to this subject. Homeopathic Medicine is defined as that which is used to produce a cure in the patient through the application of substances which are capable of producing the same symptoms the disease causes. Drugs used are given at maximum dilution since a measurable dose can be toxic. Homeopathic theory says that the greater the dilution, the greater the effect, since the properties of the drugs are ultimately transmitted by the molecular memory of water.

Given this affirmation, it would be logical to ask oneself if the effects of this medication are produced by the presence of the molecules which are there in quantities undetectable by present technology. This possibility is very much in agreement with scientific logic, especially if we keep in mind the high sensitivity of some cellular nerve receptors in living organisms. For example, it is known that human olfactory cells detect substances such as methylmercaptan in concentrations of 1/25 billionth of a milligram per milliliter of air. Why then could we not accept as a working hypothesis the possibility of the existence of some type of similar receptor at the level of the immune system capable of capturing substances in extremely low doses and reacting positively at that dosage? For example, it is known that numerous vegetable substances produce mitosis in leukocytes grown “in vitro.” Phytohaemagglutinin extracted the plant Faselous Vulgaris (red bean) is capable of stimulating the cellular reproduction of “T’ lymphocytes “in vitro” in optimum fashion in a dosage of 100 ugr/ml and has no effect at 10 ugr/ml. It also has no effect once concentration exceeds 1200 ugr/ml.

From this we can deduce that a great many substances must have similar actions at certain concentrations, such as does Concavaline A which is extracted from Concavalia Esiformis (broad bean) which stimulates a group of “T” lymphocytes different from the one which PHA (phytohaemagglutinin A) stimulates. The mytogen of Phytolacca Americana (PWM) stimulates “B” cells and a subgroup of “T” cells.

CASES: TUMORAL AREAS

The numerous cases which were treated showed a positive clinical response in greater or lesser degree. The earliest cases were studied intensively and were readied for publication.

The tumors that responded to a greater degree to our treatment, as was expected, are the ones with the greatest degree of undifferentiation; because of their antigenic characteristics and because of the greater degree of dissimilarity between them and the genotypes and antigenic characteristics of normal cells, they have more probability of eliciting an efficient immunologic response.

Histological studies which were made give us certain possible mechanisms of action which correlate with the clinical response obtained.

Microscopic studies showed the almost complete delimitation of the tumoral areas by connective-vascular structures which seem to have diverse morphologies according to their proximity to the tumor and the level of their chronological development, having at first a thick endothelial wall with lymphocytic infiltrates with convoluted nuclei that on occasion can be observed piercing the vascular walls in a fashion similar to the post-capillary venules of “T” origin of the lymphatic ganglion.

These vessels apparently evolve toward hyalinization and thinning, becoming surrounded with dense connective tissue in later stages and resulting in a kind of interconnected vascular network which is repeated in an observable manner in the different specimens which were studied. In every case, in the vicinity of the vessels and peri and intratumoral areas, the presence of numerous mastocytes was observed using the Giemsa technique (these cellular elements were considered a good prognosis in some of the work in mammary carcinoma).

Another notable characteristic is the leukocytic barrier which appears in the contact zone with the tumor. In all probability that is where all kinds of immunoactive phenomena develop, since that is where the greatest concentration of macrophage and “T” cells is evidenced.

Before continuing with the histologic descriptions we must take a brief pause in order to quote a morphologic precedent of the changes observed in these cases.

In a study, Ray and his associates in 1982 investigated the response to extra-corporeal plasma immunoabsorption with nonviable Staphylococcus Aureas in a metastasized adenocarcinoma of the colon.

On this occasion, the monthly serial biopsies of a metastasized umbilical mass demonstrated the presence of neovascularization with polymorphonuclear, eosinopphilic and plasmocellular infiltrate the first month; after that, progressive hyalization of the estroma appeared with formation of flat epithelial vessels like the ones observed in our cases and changed in the infiltrate with a greater amount of mononuclear cellular elements and plasmocytic focal areas.

The difference in our studies is in the amount and extension of the appreciable necrosis which is clearly greater than the one observed by Ray and his associates. Another difference is the absence of eosinophils in all our cases and the constant presence of mastocytes (or primed cells) which, as we mentioned, some writers associate with a better prognosis in mammary tumors.

The studies in immunohistochemistry made on the specimens allowed us to demonstrate the overwhelming presence of macrophage in tumoral borders. These were also associated to neovascular structures and to intratumoral sectors.

The number of “T” lymphocytes observed was also greater in the tumoral edges and in the perivascular area; “B” lymphocytes turned out to be less numerous and predominantly perivascular.

We are convinced of the important role that these cellular elements play in the results obtained by ENERCEL®. In many publications they are the ones believed to be capable of interacting with vascular endothelial cells (present also in great numbers in the production of interleukines II, I1 6, GM-CSF, MIF, etc.) and the important TNF (Tumor Necrosis Factor). Through the TNF, macrophages stimulate the production of other TNFmARN macrophages (ARN messenger of TNF), which with the stimulation of other leukokines is transmitted anew to the TNF protein.

In its interaction with endothelial cells, TNF produces the expression of membrane adhesion structures: ELAM 1 and ICAM 1 (endothelial cell leukocyte adhesion molecule 1 and intercellular adhesion molecule 1) which favor selectively the isolation of “T” lymphocytes to the vascular wall and their ouster from the tissues.

In addition to their cytotoxic functions, “T” cells favor the appearance and differentiation of mastocytes through IL3 (interleukin 3); the activated mastocytes interact with the fibroblasts by making them lose their inhibition by contact (demonstrated in tissue cultures), favoring collagenosis and fibrosis.

It is known that “T” lymphocytes are capable of stimulating by aggregation the affluence of cells from the “B” sector, themselves detectable by immune markers and expressed by the marked activated plasmocytes positively marked for Kappa and Lambda chains.

In summary, from the study of the cell elements present, there is evidence of a well structured and developed active immune phenomenon, of which sector “T” is mainly associated adequately with elements of sector “B” and its high necrotizing effect, demonstrated by the intense tumoral necrosis observed in the specimens studied microscopically, which reaches 80% in the case of carcinomal metastasis of renal cells. This contrasts with that observed when there is a peritumoral inflammatory reaction in cases not treated with ENERCEL® therapeutics in which the opposite occurs: numerous lymphoid elements which are incapable of destroying the tumor.

TUMORAL CELLS: THE ENERCEL® WAY

Another important element to keep in mind is the response of tumoral cells themselves: an outstanding characteristic observed in treated cases is the presence of abundant aberrant cellular, nuclear and mitotic abnormalities in the malignant cells. The changes are so evident that they suggest the findings produced by other treatments (radiotherapy or chemotherapy), although these may have not been administered to the patients studied. This probably leads the tumoral cells to a greater lability for less differentiation and toward a greater tendency to abortive mitosis. This mechanism itself feeds the immune chain again when it liberates cellular breakdown products, which surely will form part of the agents that have the capacity to elicit the antigenic response. Moreover, the cellular toxins which are the product of tumoral necrosis provoke intratumoral inflammatory and thrombotic phenomena, which increase the possibility of their destruction due to decrease of tumoral irrigation. This phenomenon is homologous to that observed in transplanted tissue rejection, in which antibodies become fixed in the vascular endothelia of the transplanted organs, provoking the activation of the fragments of the complement and serving as the substrate for the adhesion of the polymorphonuclear leukocytes which at the same time destroy the endothelial cells, permitting total or partial plaque aggregation, coagulation and vascular obstruction.

It is interesting to note in regard to this last mechanism that the arterioles and small arteries show phenomena of vasculitis but not of thrombosis. In turn, the venous vessels which theoretically remove the products of the destruction of the tumor show thrombotic phenomena.

The marked atypies already mentioned lead us to two possible analyses: on one hand we can deduce that the activation of the defense mechanism produces, by means of antibodies and cytotoxic complexes acting on the tumoral cells, intra and extracellular or metabolic alterations which increase the differentiation of atypical cells. This could be interpreted as an epiphenomenon of a general stimulation of the immune system.

On the other hand we can suppose that the ENERCEL® treatment, acting as a general mitogenic and stimulant at the level of all the cellular components of the organism, besides influencing the immune system, also influences atypical cells favoring their mitotic reproduction and provoking greater undifferentiation. In the case of malignant or very slightly differentiated tumors, this phenomenon could result in a destructive effect to the tumor itself.

We imagine that the tumoral microclimate is an unstable system in crisis, bordering in nutritional insufficiency and hypoxia, because of its characteristics and by the histological evidence by which highly malignant tumors frequently display numerous necrotic areas. Let us imagine a tumoral microenvironment bordering on hypoxia and metabolic acidosis due to lack of irrigation, stimulated to a massive active cellular reproduction.

In this model no doubt the result would be tumoral necrosis. This, in conjunction with the general action and the action on the immune system by the ENERCEL® medication, would allow the destruction of tumors by means of the metabolic mechanism on one hand and by abortive mitosis and resultant nonviable cells on the other, and finally by direct active cytotoxic destruction by the delayed (cellular) action of the immune system. At the same time, this viewpoint would present the best answer to radiotherapy and chemotherapy that 95% of our patients refer to and which we evaluate by diagnostic-imaging methods.

Radiotherapy as well as chemotherapy are highly effective in cells which are in the stage of cellular division or in the stage of the synthesis of ADN. It is evident that if the tumor is greatly stimulated, its liability will be greater.

Coupling these speculations with the idea that the ENERCEL® method is an adequate general stimulant, we can explain the improved subjective response that all our patients have had to chemotherapy. They have let us know that they notice great differences in the incidence of vomiting, nausea, headaches, etc., when they are under the ENERCEL® treatment in comparison to other methodologies.

Likewise the high and rapid recovery of the hemogram values is noteworthy in post-radiotherapy as well as in post-chemotherapy; and within the hemogram values the stimulant of monocytes is quite evident.

In treated patients the monocyte count varies from the usual 2% to 3% up to 5% or 6% and even up to 8%, this last value being in cases that respond best.

This occurred in a patient treated for multiple metastasis of kidney cell carcinoma, who demonstrated a sustained elevation of monocytes at the beginning of the second month of treatment, which continued to be 8% after 14 months, with disappearance of metastasis and even of the untreated area of the kidney.

MACROPHAGE AND TUMORAL BORDERS:

As is well known, monocytes are the circulating precursors of histic macrophages. These are cellular components capable of being stimulated experimentally to reproduce and be activated; for example, in pleuroperitonea cavities with the injection of bacterial antigens. These have been the subject of studies in animal and human experimentation through the direct activation by Cornebacterium Parvum, BCG, etc., and indirect stimulation through “T” lymphocytes by these same organisms , as a model for antitumoral immune therapeutics.

It has been known for some time that macrophages, when activated, possess divers “loci” of reception in the cellular membrane , being able to attach themselves to components coated with IgC, to a fraction of the C3G complement, to the walls of microorganisms and to vegetable lectin. Perhaps future investigations may help us find the possible compounds which at low dosages elicit the response of macrophagic activation and to find that they may be related to these vegetable lectin.

The high concentrations of macrophages found in tumoral borders have not been described by other researchers engaged in this field. On the contrary, in 1989 Norazmi et al., while making computerized video images, discovered that normal tissues possess a significantly larger number of mononuclear cells (lymphocytes, macrophages) than tumor tissues in patients with carcinoma of the colon. After analyzing the infiltrates qualitatively and quantitatively, they discovered that macrophages were absent or present in low numbers in the tumoral borders. This data coincides with that of Csiba et al. done in 1983 and with that of Row et al. conducted in 1984 regarding mammary tissues with carcinoma.

Regarding macrophage, in 1985 Mantovani and Evans declared that since these are active against tumors in and of themselves, their usual decrease in peritumoral areas could be responsible for the reduced antitumoral response of the host.

The clinical action of the effects of the ENERCEL® medication can be seen in the numerous cases as that of a patient with metastasis of renal carcinoma who showed a highly favorable evolution of his cerebral metastasis when in December 1, 1989, he had shown a terminal picture, accompanied by cutaneous, hepatic and pancreatic metastasis. He was treated with only 5000 cranial Rads and no other therapy besides the ENERCEL® method. We find him 14 months later in a perfect state without hepatic and pancreatic metastasis and with a reduction of the cerebral metastasis showing scar foci which seem to be calcified.

A cutaneous metastasis which was excised after 4 months under the ENERCEL® treatment, which had shrunk to half of its original size without any additional local or general treatment, allowed us to conduct one of the observations with immune marking.

Another very interesting case allowed us to observe the reduction of a hepatic metastasis of mammary adenocarcinoma until it disappeared.

Another very interesting case if that of a patient with undifferentiated Cavum carcinoma, who during radiotherapy showed tumoral increase instead of decrease. Upon beginning ENERCEL® treatment he showed a rapid clinical and tomographic improvement, and is now in perfect general state without recidivism of his disease.

ENERCEL®: A JOINT THERAPEUTIC

There are many cases like the ones cited in which ENERCEL® therapeutics, either alone or in conjunction with radiotherapy or chemotherapy, have been able to reduce and even remove metastasis and primary tumors. Its action varies in relation with four aspects of the disease as follows:

1) The stage of invasion of the malignancy and, above all, the whole volume of the tumoral mass. The larger the tumoral mass, the more difficult it is to cure, while the opposite is true in smaller masses (even in cases of cerebral or hepatic metastasis when these are isolated or small).

2) The type of tumor. The more undifferentiated the malignancy, the better the evolution and histology. The cases with the least specific antitumoral response (even improving the general state of the patient) are found in well differentiated tumors that have a low degree of aggressiveness.

This suggests that when the histological type is more similar to the normal cells of the human organism the possibility of exhibiting antigens capable of eliciting an adequate immune response is smaller.

3) The age and general state of health of the patient are important. The younger, the greater the response; the healthier, the better possibility of reaction. We assume that this has to do with the integrity of the immune system.

It is known that in every species old age results in the decrease of defense mechanisms. It is probable that there is a total loss of the clones of the mother cells immunologically excitable in the bone marrow, the spleen and the lymphatic ganglia (organs which tend to atrophy and decrease in old age).

The treatments associated with ENERCEL® therapeutics are no doubt responsible for the diversity of results observed. For example we are in a position to propose, notwithstanding that in order to come to more definitive conclusions more research is needed, that the adjunct of radiotherapy in localized sectors which do not affect the individual, globally altering his immune system, is highly positive. The more spectacular cases in tumoral remission have been obtained with this adjunct. On the other hand, chemotherapy even with ENERCEL® medication, becomes attentuated rapidly as far as its subjective progress (vomiting, nausea, headaches, appetite, general state( and its subjective progress (hemogram, resistance to infections, capacity for physical activity, etc. does not show spectacular reduction of the tumoral masses. An exception in this tendency has been in some cases of carcinoma of small pulmonary cells (oat cell carcinoma) and other undifferentiated tumors of the neuroblastoma and acute leukemia types in children which show marked improvement.

The balancing of these four variables, that is: 1) tumoral size, 2) histological type, 3) age and general state, and 4) adjunct therapy, give us the necessary elements for a preliminary prognosis of the possibilities of treatment in each case.

We are well aware that this is a subject which must be intensely studied in the future with the same or even greater intensity than the basic research (mechanism of action) in order to be able to face with certainty the treatment of each tumoral type or each particular case.

At present, a short five years in which the ENERCEL® method has been in use, we are not in the position to advise the patient to abandon any of the classical methods of treatments available. The latter in many instances are merely palliative without stopping the advance of the disease, while at the same time they destroy the patient’s immune system so that when the therapy is suspended or no other therapy becomes available, the tumoral progression is inexorable because the defense mechanisms and the general state of the patient are devastated without having achieved the elimination of the neoplasm.

In concluding this brief introduction to ENERCEL® therapeutics, we can state that we find ourselves with a method of treatment against neoplasms which is innocuous and has many advantages due to the ease of its administration, high degree of tolerance, and its proven beneficial effects.

Among these effects we can cite:

1) An increase in the antitumoral immune activity which is demonstrated histologically in the increase of the destruction and necrosis of tumors, with marked difference in the composition of the peritumoral mononuclear inflammatory infiltrate, the opposite of that observed in cases not treated, with an increase of macrophage and “T” lymphocytes.

2) A better tolerance in comparison with unusual oncological treatments (radiotherapy and chemotherapy), demonstrated by the subjective manifestations of the patients and by laboratory tests, with a more rapid recovery of the hemogram and general state.

3) Objective reduction of the tumor size through imaging studies conducted on patients treated with ENERCEL® therapeutics, either by itself or in conjunction with other classical methods.

4) Extension of the life expectancy of patients diagnosed as terminal. This extension in all cases exceeded the forecast by several months and in some cases a cure was achieved.

Given these facts, we tend toward a deepening of our studies of the mechanisms of action, which almost surely are related to the stimulation and activation of macrophage and “T” cells by one or several of the substances we use.

These mechanisms have homolog in, for example, the stimulating activity of CD4T lymphocytes (“T” helper) in humans, which is contained in Jacalina, which is extracted from the seeds of Astrocarpus Heterophillus. Moreover the presence of receptors for nonopsonized sheep erythrocytes has been effectively demonstrated, lectin-similes in murine macrophage; a system that is capable of effecting hemopoiesis and immunocompetence of macrophages through interaction with sialinized glucoconjugates.

All this information leads us to plan future studies in stimulation in vitro of macrophage and “T” lymphocytes, as a means to obtain convincing certification of the mechanism of action at a level of basic investigation and also to determine the serial lymphocytic subgroups in patients under treatment.

The marked atypies already mentioned lead us to two possible analyses: on one hand we can deduce that the activation of the defense mechanism produces, by means of antibodies and cytotoxic complexes acting on the tumoral cells, intra and extracellular or metabolic alterations which increase the differentiation of atypical cells. This could be interpreted as an epiphenomenon of a general stimulation of the immune system.

On the other hand we can suppose that the ENERCEL® treatment, acting as a general mitogenic and stimulant at the level of all the cellular components of the organism, besides influencing the immune system, also influences atypical cells favoring their mitotic reproduction and provoking greater undifferentiation. In the case of malignant or very slightly differentiated tumors, this phenomenon could result in a destructive effect to the tumor itself.

We imagine that the tumoral microclimate is an unstable system in crisis, bordering in nutritional insufficiency and hypoxia, because of its characteristics and by the histological evidence by which highly malignant tumors frequently display numerous necrotic areas. Let us imagine a tumoral microenvironment bordering on hypoxia and metabolic acidosis due to lack of irrigation, stimulated to a massive active cellular reproduction.

In this model no doubt the result would be tumoral necrosis. This, in conjunction with the general action and the action on the immune system by the ENERCEL® medication, would allow the destruction of tumors by means of the metabolic mechanism on one hand and by abortive mitosis and resultant nonviable cells on the other, and finally by direct active cytotoxic destruction by the delayed (cellular) action of the immune system. At the same time, this viewpoint would present the best answer to radiotherapy and chemotherapy that 95% of our patients refer to and which we evaluate by diagnostic-imaging methods.

Radiotherapy as well as chemotherapy are highly effective in cells which are in the stage of cellular division or in the stage of the synthesis of AND. It is evident that if the tumor is greatly stimulated, its lability will be greater.

Coupling these speculations with the idea that the ENERCEL® method is an adequate general stimulant, we can explain the improved subjective response that all our patients have had to chemotherapy. They have let us know that they notice great differences in the incidence of vomiting, nausea, headaches, etc., when they are under the ENERCEL® treatment in comparison to other methodologies.

Likewise the high and rapid recovery of the hemogram values is noteworthy in post-radiotherapy as well as in post-chemotherapy; and within the hemogram values the stimulant of monocytes is quite evident.

In treated patients the monocyte count varies from the usual 2% to 3% up to 5% or 6% and even up to 8%, this last value being in cases that respond best.

This occurred in a patient treated for multiple metastasis of kidney cell carcinoma, who demonstrated a sustained elevation of monocytes at the beginning of the second month of treatment, which continued to be 8% after 14 months, with disappearance of metastasis and even of the untreated area of the kidney

Buenos Aires
Argentina, July 1991 Cesar Bertacchini, M.D. et al.

 

© 2018 Enercel | Nature Advanced - Disclaimer | Privacy Policy | Terms of Service
Top