Below you will find Dr. Mirko Beljanski’s 133 Research Publications
ABSTRACT IN ENGLISH: The plant-derived anticancer agent PB-100 (Beljanski® Pao extract) selectively destroys cancer cells, even when multidrug resistant; yet, it does not inhibit normal (non-malignant) cell multiplication. Testing of PB-100 on sixteen cell lines, several multidrug resistant, as well as on five normal cell lines, confirmed our previous results. Flavopereirine and dihydroflavopereirine, the active principles of PB-100, were chemically synthesized and displayed the same selectivity for tumor cells as the purified plant extract, being active at even lower concentrations. List of cell lines tested: brain (4), ovary (2), breast (2), prostate thyroid (2), colon (2), pancreatic, hepatic, kidney, skin, liver
ABSTRACT: We investigated in vitro the effect of six different substances present in the brain on two human cell lines: U251-BCNU-resistant glioblastoma cells, derived from a highly malignant cerebral tumor, and, as their normal counterparts, CRL 1656 astrocytes. The cytokines IL-4 and IL-10 (alone or together with IL-6), the catecholamine neuromediators dopamine and epinephrine, the steroid hormones progesterone and testosterone all significantly stimulated multiplication of the glioblastoma cells, but enhanced to a much lesses extent multiplication of normal astrocytes. The selective anticancer agent PB-100* inhibited these stimulatory effects. In addition, it could dose-dependently kill over 98% of the malignant cells while not affecting normal cells.
ABSTRACT: When past the stage amenable to surgery, melanoma and its metastases are, as a rule, treated with chemotherapy, which is largely unsuccessful. In this report, experimental evidence is presented demonstrating that, in vitro, two selective anticancer agents, PB-100 and BG-8, dose dependently destroy human G-361 melanoma cells, but do not affect human non malignant CCD-974Sk fibroblasts used as controls. Trace metal compounds, present, often in abnormal amounts, in the cancer cell and/or its environment, are known to influence its proliferation. Assays were carried out using highly elevated amounts of ferritin, iron chloride or zinc chloride. Ferritin proved differentially mitogenic for melanoma cells and fibroblasts. Its activity was inhibited by both anticancer agents, which however tended to become less efficacious in its presence. FeCl3 was more moderately, but equally, mitogenic for malignant and normal cells, yet it impaired antiproliferative activity of PB-100 and inhibited that of BG-8. ZnCl2 exhibited a selective antiproliferative activity on the malignant melanoma cells; it did not compete with PB-100 or BG-8. Specific recognition and destruction of malignant cells by the two anticancer agents are discussed.
ABSTRACT: Selective targeting to diseased cells, ensuring nontoxicity for normal cells, are the master words for anticancer and antiviral therapies. Yet little progress has been made on these lines and adverse side effects are still the rule. After having designed a rapid and simple in vitro screening test (Oncotest), we were able to find a number of plant derived, chemically well defined substances which selectively inhibit cancer cell multiplication without affecting normal cells. Activity of these agents is based on the fact that, as we discovered after extensive comparison of DNAs from cancer cells and their normal counterparts, cancer DNA is characterized by its highly relaxed, destabilized secondary structure, within which H-bond breakage is evidenced by 260 nm UV absorption, always distinctly higher than that of normal DNA. Our anticancer agent easily bind to the “open” cancer DNA chains; in contrast, they do not bind to normal DNA chains, which are “closed” most of the time.
ABSTRACT: Selectivity of the anticancer agent PB-100 for malignant cells, already demonstrated using cell growth and viability evaluation, is now confirmed by microscopic observations. PB-100 is easily detected inside cells by its yellow color under visible light and by its blue fluorescence; it may be measured in isolated nuclei using its characteristic UV absorbance. After short treatment of human BCNU-resistant glioblastoma cells (U 251) and normal astrocyte controls (CRL 1656), PB-100 accumulates in the malignant cell nucleus, particularly concentrating in the multiple nucleoli and rapidly inducing glioblastoma cell death, whilst, in contrast, the anticancer agent does not even enter normal cells. We had already shown that PB-100 binds to DNA of cancer cells, but not to that of normal cells. In vitro tests described in this report indicate that PB-100 binds to purine bases, but not to pyrimidines, of various ribopolymers and its binding to purine rich nucleic acid stretches is inferred.
ABSTRACT: The multifunctional cytokine interleukin-6 behaves as a growth factor for various malignancies. It is produced in significant amounts by glioblastoma cells. When exogenous IL-6 is added (pg/ml) to culture medium of human glioblastoma cells and normal (non malignant) astrocytes used as controls, it exerts a dose dependent and differential effect on these two cell lines. Enhancement of cell proliferation is twice as high for glioblastoma cells as for astrocytes. In vitro, the novel anticancer agent PB-100 (mu g/ml) dose dependently inhibits this stimulatory activity. In addition, increasing PB-100 concentrations finally induce death of the malignant cells, yet do not impede multiplication of normal astrocytes. PB-100 does not abolish IL-6 production by cells, but keeps its level down to physiological values. PB-100 should therefore find its place in therapies requiring control of IL-6 production.
ABSTRACT: The multifunctional cytokine interleukin-6 behaves as a growth factor for various malignancies. It is produced in significant amounts by glioblastoma cells. When exogenous IL-6 is added (pg/ml) to culture medium of human glioblastoma cells and normal (non malignant) astrocytes used as controls, it exerts a dose dependent and differential effect on these two cell lines. Enhancement of cell proliferation is twice as high for glioblastoma cells as for astrocytes. In vitro, the novel anticancer agent PB-100 (mu g/ml) dose dependently inhibits this stimulatory activity. In addition, increasing PB-100 concentrations finally induce death of the malignant cells, yet do not impede multiplication of normal astrocytes. PB-100 does not abolish IL-6 production by cells, but keeps its level down to physiological values. PB-100 should therefore find its place in therapies requiring control of IL-6 production.
ABSTRACT: Major drawbacks to present-day cancer chemotherapy are its intrinsic lack of selectivity for tumour cells, resulting in severe damage to normal rapidly dividing cells, and the widespread emergence of drug resistance. Here experimental evidence is presented demonstrating that PB-100, a beta-carboline alkaloid, selectively inhibits in vitro multiplication of human BCNU-resistant glioblastoma cells (U251), but has no effect on normal astrocyte (CRL 1656) multiplication. PB-100 activity is dose-dependent. In the presence of ferritin or CaCl2, which are highly mitogenic for glioblastoma cells, higher doses of the alkaloid are required to inhibit multiplication completely. PB-100 is one of several compounds which were selected for their specific action on cancer DNA and cells, together with lack of activity on normal DNA and cells. Both the selectivity of PB-100 and its ability to overcome drug resistance stem from its effect on cancer DNA secondary structure. This activity is described and discussed, and therapeutic applications are mentioned..
ABSTRACT: Cell function and differentiation are the outcome of multiple and complex events. Information contained in the genes is transferred to the enzymes and machinery responsible for protein synthesis via sophisticated biochemical pathways, some of which, despite their intricacy, are now well documented. Conversely, genes receive information which modulates their activity. Many different molecules are able to bind to nucleic acids (deoxyribonucleic acid, DNA, and ribonucleic acid, RNA), thereby modifying gene activity as well as that of various enzymes connected with it. It is well established that the effect of endogenous or exogenous molecules on such fundamental processes of cell life as DNA duplication, transcription and translation may dramatically affect other biochemical processes both downstream and upstream. Binding of any molecule to DNA may influence cell life “for better or for worse”.
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ABSTRACT: La sélectivité d’action des substances est une notion aussi nouvelle que fondamentale. Alors que toutes les autres solutions jusqu’ici offertes sont brutales, toxiques (les médicaments s’incorporant souvent sans retour dans les gènes), est offert une alternative ciblée, de toute sécurité, multifocale afin que le virus soit détruit, l’immunité protégée et l’équilibre rétabli, seules conditions pour une vie de qualité se dirigeant jour après jour vers la “guérison”..
Deutsche Zeitschrift für Onkologie 5, 22, 1990, pp. 145-152.
ABSTRACT: About one third of patients with various malignant diseases were found to have extractable amounts of DNA in their plasma whereas no DNA could be detected in normal controls. Using the test established by one of us (M.B.), which is based on decreased strand stability of cancer cell DNA, we have found that several plasma DNA originate from cancer cells.
Médecines nouvelles, 15, 1986, pp. 57-86.