On the Influence of Stilbamidine Upon Myeloma Cells

Snapper, I.; Schneid, B.

doi:10.1182/blood.v1.6.534.534

Cited by 25 publications

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“…Special interest attaches to the negative result obtained with 4-wopropylstilbene, as indicating the non-interchangeability of the amino and isopropyl groups in spite of their similarity as electron donors, and with the two benzylamines tested (see Kon 1948). The lack of activity in 4-amidinostilbene is of similar interest, as also in relation to the effects of stilbamidine (4:4/-diamidinostilbene) upon myeloma, recently described by Snapper & Schneid (1946); in another series of experiments, no action upon the growth of the Walker tumour was detected as a result of treatment with stilbamidine or its 2-amino-, 2-chloro-or 2-iodo-derivatives.…”

Section: (Iii) Replacement Of the Polar Groupmentioning

confidence: 82%

The growth-inhibitory and carcinogenic properties of 4-aminostilbene and derivatives

Haddow

Harris

Kon

et al. 1948

Phil. Trans. R. Soc. Lond. A

104

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Plates 2 t o 4] CONTENTS PAGE I. Introduction 148 II. Influence upon growth-inhibitory ACTION OF MODIFICATIONS IN CHEMICAL CONSTITUTION 151 1. Modifications involving the polar group 151 2. Modifications of the ethylene bridge 152 3. Substitution affecting ring A 160 4. Substitution affecting ring B 160 5. Stereoisomerism 162 6. Heterocyclic modifications 162 7. Conclusions 162 Marked inhibition of the growth of the Walker rat carcinoma 256 is produced by administration of 4-aminostilbene and of 4-dimethylaminostilbene. From similar experiments with the Crocker sarcoma 180, the carcinoma C63, and spontaneous mammary cancer, it appears that the growthinhibitory action of these compounds is much less pronounced in mice. In a dosage of 200 to 250 mg./kg. in the rat, both 4-amino-and 4-dimethylaminostilbene produce (a) gastro-intestinal submucous haemorrhage most evident in the pyloric portion of the stomach, (b) haematuria, and (c) haemolymph changes, while the former compound induces methaemoglobinaemia in addition.Using the Walker rat carcinoma 256 as the biological test object, a series of derivatives of 4-amino stilbene has been examined to determine the relationship between the growth-inhibitory effect and chemical constitution. / The great majority of the active compounds can be defined as stilbenes with a basic substituent, the position of which is of paramount importance; thus o-dimethylaminostilbene is very much less active than the />-isomeride, and the ra-compound is completely inactive. A further essential feature is the ethylene bridge, since activity disappears when either of its hydrogen atoms is substituted, when the bridge is reduced, when it is extended to contain three or four carbon atoms, or when either methine group is replaced by a nitrogen atom. Compounds in which the ethylene bridge is absent, or is replaced by oxygen or sulphur, are also inactive, and activity is further dependent upon the Irans configuration of the molecule about the ethylenic bond, and to a large extent upon a free p' -position. These and other facts have suggested the working hypothesis that one of the features required for activity is an unbroken conjugation of the amino group with both nuclei, enabling the compound to assume some dipolar quinonoid character, which depends, among other things, on the co-planar arrangement of the two benzene nuclei which characterizes the trans form of the stilbenes. PAGE I I I . T h e u l t r a -v io l e t a b s o r p t io n s p e c t r o s c o p y o f s e l e c t e d s t ilb e n e s 165 8. General theoretical considerations 165 9. Technique and results 166 10. Discussion 168 IV . T he carcinogenic action o f 4-amino stilbene AND DERIVATIVES 175 V . General discussion 177 VI. Experimental: preparation of stil benes 184 R eferences 192 D escription of Plates 195 V ol. 241. A. 830. (Price 155.) 19 [animals, the tumour weights at the 11th day totalled 262-4 g. (mean 23:8 g.) in the latter series, against a total of only 4-0 g. in the former. In a third experiment, twelve implanted rats rec...

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Section: (Iii) Replacement Of the Polar Groupmentioning

confidence: 82%

The growth-inhibitory and carcinogenic properties of 4-aminostilbene and derivatives

Haddow

Harris

Kon

et al. 1948

Phil. Trans. R. Soc. Lond. A

104

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“…However, before selective immunodepressants were ready for use, selective cytostatic drugs had already been available for some time. These are drugs capable of inhibiting to varying degrees the proliferation of only one blood cell line, such as busulfan, a selective cytostatic drug which targets the granulocytic cell line which was introduced by Alexander Haddow and Geoffrey M. Timmis (67) in 1953, and stilbamidine, selective sytostatic which targets the plasmocytic line, introduced by Isidor Snapper (68) as long ago as 1946. Among immunodepressants, the first example of a selective drug could be considered to be cyclosporin.…”

Section: Surveymentioning

confidence: 99%

Short story of antirheumatic therapy.VIII. The immunodepressants

Pasero¹,

Marson²

2012

Reumatismo

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The use of immunosuppressive drugs in rheumatology is fairly recent, starting just after the Second World War with the introduction of the first alkylating agents in oncohematology. When it became clear that some rheumatic diseases, particularly rheumatoid arthritis and systemic lupus erythematosus, showed an immune-mediated pathogenesis, including proliferation of immunocompetent cells, an application was soon found for immunosuppressive drugs in their treatment. This review outlines the historical milestones that led to the current use of drugs belonging to the major groups of immunosuppressants, i.e. alkylating agents (cyclophosphamide), folic acid (methotrexate) and purine (azathioprine) antagonists. We will also talk about the history of cyclosporin A, the first "selective" immunosuppressive agent, and that of some immunoactive drugs used more recently in rheumatology, such as mycophenolate mofetil, dapson and thalidomide, is briefly described.

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Chemotherapy of Malignant Neoplastic Diseases

Reinhard¹

1950

JAMA

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Chemotherapy of cancer has been studied intensively in recent years. Attempts to inhibit tumor growth by means of drugs have been made since ancient times, but not until the last decade have potent carcinolytic compounds been discovered which can be tolerated by animals and human beings in at least partially effective doses. The enormous literature which has now accumulated on this subject has been summarized in several recent reviews.1 Drugs which have aroused a great deal of interest include Serratia marcescens (Bacillus prodigiosus) polysaccharide, KR (carcinolytic substance of Trypanosoma cruzi, named after Klyueva and Roskin), antireticular cytotoxic serum (ACS), stilbamidine (4,4\m='\-stilbenedicarboxamidine) and ethylstibamine (neostibosan\s=r\), folic acid conjugates, folic acid antagonists, urethane and the nitrogen mustards (2-chloroethyl amines). The data available at present indicate that all but the last three of these substances are either biologically inactive or are too toxic to be practical for clinical application. Neither the radioactive isotopes nor endocrine substances used in therapy of cancer will be discussed in this paper, as it is considered that they do not fall within the scope of the term chemotherapy.At present, chemotherapy of cancer is at best pallia¬ tive and retardation of tumor growth, when it occurs at all, is temporary. The intense research activity in this field is apparently based on the assumption that it is theoretically possible to destroy completely or prevent the multiplication of malignant cells by the administra¬ tion of drugs without irreparably damaging normal cells. However, some of the most experienced investigators in the field of cancer research doubt whether cure of cancer in this sense is within the realm of possibility,2 and certainly this goal is not apt to be achieved within the near future. STILBAMIDINE AND ETHYLSTIBAMINEStilbamidine is known to be effective in the treatment of kala-azar. As both kala-azar and multiple myeloma are characterized by hyperglobulinemia, Snapper2began treating multiple myeloma with this drug. The rationale for this use of stilbamidine is not clear, as the drug acts directly on the parasite causing kala-azar and has no effect on the abnormal protein ; furthermore, the abnormal protein in kala-azar is not the same as the abnormal protein in myeloma.23 Nevertheless, Snapper observed that, after administration of the drug, large basophilic inclusion bodies appear in the myeloma cells but not in any other cells in the bone marrow, and these bodies have been shown to contain large amounts of ribose nucleic acid.24 The suggestion is made that stilbamidine may specifically dissociate the nucleoproteins of myeloma cells. Snapper reported that concomitant with the appearance of the granules clinical improvement frequently occurred, and the drug seemed to have a specific influence on the severe bone pain of this disease. Bone pain improved in 80 per cent of the cases.Karnofsky ld quoted an analysis by Gibson and Pogge of a pooled survey' ...

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On the Influence of Stilbamidine Upon Myeloma Cells

Cited by 25 publications

References 0 publications

The growth-inhibitory and carcinogenic properties of 4-aminostilbene and derivatives

The growth-inhibitory and carcinogenic properties of 4-aminostilbene and derivatives

Short story of antirheumatic therapy.VIII. The immunodepressants

Chemotherapy of Malignant Neoplastic Diseases

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