123 – PB100: A Potent and Selective Inhibitor of Human BCNU Resistant Glioblastoma Cell Multiplication

Authors : M. BELJANSKI, S. CROCHET, M.S. BELJANSKI
Anticancer Research, vol.13, n°6A, Nov. Dec. 1993, pp. 2301-2308.

Available online in French, summary in English

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..

123 - PB100: A Potent and Selective Inhibitor of Human BCNU Resistant Glioblastoma Cell Multiplication

122 – A New Approach to Cancer Therapy

Authors : M. BELJANSKI
Proceedings of the international seminar: Traditional Medicine: a Challenge of the 21st Century, 7-9 Nov. 1992, Calcutta (ed. in chief Biswapati Mukherjee).

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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”.

122 - A New Approach to Cancer Therapy

119 – Reverse Transcriptases in Bacteria: Small RNAs as Genetic Vectors and Biological Modulators

Authors : M. BELJANSKI
Brazil. J. Genetics, 14, 4, 1991, pp. 873-896.

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ABSTRACT: In 1970, with my group at the Pasteur Institute in Paris, I observed that showdomycin resistant Escherichia coli cells excrete into their culture medium a small RNA, about 160 nucleotides long, rich in purine bases. This RNA transforms wild bacteria (E. coli and Agrobacterium tumefaciens) into transformants which exhibit new stable biochemical and physical characteristics. Thus A tumefaciens once transformed by E. coli transforming RNA, partially or often totally loses its oncogenic potentialities and acquires new properties. It appeared that reverse transcriptase might give transforming RNA the means of integrating into the genome of the transformed organisms the modifications it vectored. We demonstrated (1971-1972) that bacterial reverse transcriptase was involved in this process. In the course of our studies on bacterial transformation, we devised a technique which led to the discovery, first of RNA free reverse transcriptase in bacteria, then of RNA-bound reverse transcriptase which is easily distinguishable from DNA-dependent-DNA-polymerase. In 1989 several american scientists rediscovered reverse transcriptase in E. coli.

119 - Reverse Transcriptases in Bacteria: Small RNAs as Genetic Vectors and Biological Modulators

118 – RNA Fragments (RLB) and Tolerance of Cytostatic Treatments in Hematology: A Preliminary Study about Two Non-Hodgkin Malignant Lymphoma Cases

Authors : DONADIO, R. LORHO, J.E. CAUSSE, T. NAWROCKI, M. BELJANSKI
Deutsche Zeitschrift für Onkologie, 23, 2, 1991, pp. 33-35.

Available in French only

ABSTRACT: Assays were carried out with short-chain RNA fragments in order to determine whether they can prevent or decrease chemotherapy-induced neutropenia and thrombopenia, as well as to evaluate side effects. We studied both first patients, 65 and 77 years old with non-Hodgkin lymphoma. The short-chain RNAs, administred bysublingual way every second day, appear useful in this indication. Neutrophils and platelets are significantly increased. In addition, tolerance of the RNA fragment is good and no side effect is observed. Chemotherapy protocols could be followed without treatment.

118 - RNA Fragments (RLB) and Tolerance of CytostaticTreatments in Hematology: A Preliminary Study about Two Non-Hodgkin Malignant Lymphoma Cases

117 – Cancer et Sida. Nouvelles approches thérapeutiques

Authors : M. BELJANSKI
5èmes Entretiens Internationaux de Monaco, 21-24 novembre 1990 (ed. du Rocher), pp. 25-37.

Available in French only

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”..

117 - Cancer et Sida. Nouvelles approches thérapeutiques

115 – Résultats préliminaires de l’emploi des trois alcaloïdes sur des carcinomes prostatiques

Authors : M. BELJANSKI, M.S. BELJANSKI, M. GRANDI*
In Tumori, Institute Nationale per le studio ed la cura dei tumori (ed. Lambrosiana), Vol. 75, suppl. 4, 1989.
“Resultati preliminari dell’impiego di tre alcaloidi nel carcinoma prostatico”
*Dr. Maurizio GRANDI, membre de l’académie des sciences de Rome

Available in French only

ABSTRACT: Nous avons étudié l’effet des alcaloïdes : Alstonine, Serpentime et Sempervirine, en association avec la radiothérapie sur 5 patients ayant un carcinome prostatique. Ces résultats confirment ceux déja obtenus en laboratoire sur la reconnaissance sélective du DNA néoplasique.

115 - Resultati preliminari dell’impiego di tre alcaloidi nel carcinoma prostatico

114 – Neoplastic Characteristics of the DNA Found in the Plasma of Cancer Patients

Authors : M. STROUN, P. ANKER, P. MAURICE, J. LYAUTEY, C. LEDERREY, M. BELJANSKI
Oncology, 46, 1989, pp. 318-322.

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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.

114 - Neoplastic Characteristics of the DNA Found in the Plasma of Cancer Patients

113 – Reversible biophysical changes of DNAs from in vitro cultured non-tumour cells

Authors : M. BELJANSKI, L. LE GOFF, M. WICKER
Med. Sci. Res., 16, 1988, pp. 359-361.

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ABSTRACT: We have previously shown that DNA fom plant Crown-gall tumour tissues is highly relaxed and thereby very susceptible to various DNA-destabilizing agents which, in contrast, do not affect DNA from healthy tissues. In vitro DNA strand separation (chain unpairing), the rate of in vitro DNA synthesis and in vivo increase in tumor cell multiplication are colsely correlated. Here we report that plant non-tumour cell DNA may temporarily undergo conformational changes when these cells are cultured in vitro in the presence of opines (octopine, nopaline, lysopine which accumulate in Crown-gall tissues or dl-ethionine (a known carcinogen in mammalian tissues). The induced DNA double-strand destabilisation and consequent increase in template activity are shown to be reversible under our experimental conditions.

113 - Reversible biophysical changes of DNAs from in vitro cultured non-tumour cells

111 – Particular RNA primer from growth medium differentially stimulates in vitro DNA synthesis and in vivo cell growth of Neurospora crassa and its slime mutant

Authors : M. BELJANSKI, S.K. DUTTA
Current Genetics, 12, 1987, pp. 283-289

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ABSTRACT: Purine rich small “RNA-primer” molecules (about 10-12 nucleotides), secreted into the growth medium of 3-h germinated conidia of N. crassa, strongly stimulated a concentration-dependent in vitro DNA synthesis of N. crassa slime mutant as well as DNAs from the human cancer cells but did not affect that from normal cells. These “RNA-primer” molecules stimulated also in vivo cell growth of N. crassa slime mutant, but not of the N. crassa wild type. Our studies suggest that DNAs from the slime mutant of N. crassa as well as DNAs from human cancerous cells provide increased sites for enhanced in vitro and in vivo replication of DNAs. “RNA-primer” molecules can be hydrolyzed by T1 RNase but not by pancreatic RNase.

111 - Particular RNA primer from growth medium differentially stimulates in vitro DNA synthesis and in vivo cell growth of Neurospora crassa and its slime mutant

110 – Differential Synthesis and Replication of DNA in the Neurospora crassa Slime Mutant versus Normal Cells: Role of Carcinogens

Authors : M. BELJANSKI, S.K. DUTTA
Oncology, 44, 1987, pp. 327-330

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ABSTRACT: Small quantities of carcinogens, dl-ethionine, thiotepa, actinomycin D, and 1-(2-chloroethyl-3-cyclohexyl)-1-nitrosourea (CCNU) stimulated in vitro deoxyribonucleic acid (DNA) synthesis of the slime mutant of Neurospora crassa, while there was practically no effect on the DNA from the normal wild type 74A strain. All of these compounds caused increased strand separation in the mutant DNA of N. crassa, but no separation of normal DNA strands. The growth (in vivo tests) of the N. crassa slime mutant, but not its wild type, was markedly increased when nontoxic concentrations of one of the carcinogens (dl-ethionine) tested were present in the growth medium. These observations suggest that, unlike the wild type N. crassa, the slime mutant allows an excessive and unscheduled replication, indicating destabilized nature of its DNA.

110 - Differential Synthesis and Replication of DNA in the Neurospora crassa Slime Mutant versus Normal Cells: Role of Carcinogens

109 – Terminal deoxynucleotidyl transferase and ribonuclease activities in purified hepatitis-B antigen

Authors : M. BELJANSKI
Med. Sci. Res., 15, 1987, pp. 529-530.

Available in English only

ABSTRACT: Terminal deoxyribonucleotidyl transferase (TdT) (EC 2.7.7.31) was defined as a template independent DNA polymerase that binds deoxyribonucleoside-5′-monophosphates (dNMP) in sequential addition to the 3’OH end of the DNA initiator. TdT may exhibit its activity in the presence of oligodeoxyribopolymers. This enzyme has been found in embryonic calf thymus gland, cortical thymocytes, brain, primitive bone marrow cells, peripheral blood lymphocytes in certain forms of acute leukemia, neuroblastoma and retroviruses. A model was proposed according to which TdT may generate somatic mutations in the variable region of immunoglobulin genes. Recently, the mutagenic potential of TdT has been evaluated: TdT inserts noncomplementary bases during repair synthesis by DNA polymerase. The present work shows that purified and commercially available hepatitis-B antigen (vaccine) contains a very active TdT and ribonuclease (RNase).

109 - Terminal deoxynucleotidyl transferase and ribonuclease activities in purified hepatitis-B antigen