Differences between vinblastine and vincristine in distribution in the blood of rats and binding by platelets and malignant cells

Gout, Peter W.; Wijcik, Lynda L.; Beer, Charles T.

doi:10.1016/0014-2964(78)90222-0

Cited by 33 publications

(12 citation statements)

References 13 publications

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“…3) was readily extracted from homogenized cells by methylene chloride, indicating that the radioactivity was not covalently bound to non-lipoidal cellular material. Furthermore, isotopic dilution analysis by methods already described (Gout et al, 1978) revealed that over 95 % of the cellular radioactivity was due to unchanged VCR.…”

Section: Resultsmentioning

confidence: 99%

Vinblastine and vincristine ‐ growth‐inhibitory effects correlate with their retention by cultured Nb 2 node lymphoma cells

Gout¹,

Noble²,

Bruchovsky³

et al. 1984

Intl Journal of Cancer

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Vinblastine (VLB) and vincristine (VCR) have been compared with respect to their inhibitory effects on the growth of cultured Nb2 node rat lymphoma cells and their binding and release by these cells. When examined over a wide concentration range, the two alkaloids were found to be almost equally effective in inhibiting culture growth, providing they were continuously present in the incubation medium. A striking difference was found, however, when the cells were incubated for short periods with the alkaloids and then restored to alkaloid-free medium for further incubation. Cells treated with VCR (5 X 10(-9) g/ml) for 3 h and washed free of extracellular alkaloid failed to resume normal proliferation during a subsequent 48 h incubation period in alkaloid-free medium. In contrast, cells treated with VLB at a higher concentration (5 X 10(-8) g/ml) and for a longer time (7 h), rapidly resumed growth in alkaloid-free medium. Binding studies, using (3H)VLB and (3H)VCR, showed that when cells were incubated continuously with the alkaloids at a given concentration, they bound equal amounts of the drugs. When labelled cells were resuspended in alkaloid-free medium, VLB was released very readily by the cells, whereas VCR was tenaciously retained. The findings indicate that the growth-inhibitory effects of VLB and VCR are related to the amount of alkaloid associated with the cells and that the long-lasting effects of VCR, relative to VLB, are very likely due to the retention of VCR by the cells when the extracellular alkaloid levels decline. The study also suggests that, in the treatment of malignancies, VLB could be more effective if its extracellular levels were maintained, e.g. by continuous administration.

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Section: Resultsmentioning

confidence: 99%

Vinblastine and vincristine ‐ growth‐inhibitory effects correlate with their retention by cultured Nb 2 node lymphoma cells

Gout¹,

Noble²,

Bruchovsky³

et al. 1984

Intl Journal of Cancer

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“…The VCR or VLB-pla-telet complex carries a targeted injury to macrophages and may reduce the risk of un toward effects by lowering the doses of the cytotoxic drug. VCR may be more suitable than VLB for loading platelets since the lat ter is partially released from loaded platelets when they are resuspended in vinca-free plasma, whereas all the VCR initially bound is retained [10].…”

Section: Discussionmentioning

confidence: 99%

“…Thus, a method has been devised to carry a selective injury to macro phages, using infusions of periwinkle alka loid-loaded platelets [2], A major receptor for the biologically active periwinkle alka loids is tubulin, the protein subunit from which cellular microtubules are assembled [16]. Platelets are very rich in microtubules and thus they are the cellular carriers of a major proportion of the infused circulating alkaloids [10]. Vinca alkaloid-loaded plate lets allow the selective delivery of large amounts of vinca alkaloids into macro phages, leading to their dysfunction or death and to a subsequent alleviation of platelet destruction [2].…”

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Infusion of Vincristine-Loaded Platelets in Acute ITP Refractory to Steroids: An Alternative to Splenectomy

et al. 1981

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Three infusions of vincristine-loaded platelets were carried out in a young man with acute idiopathic thrombocytopenic purpura (ITP) refractory to steroids. This procedure, used until now only for chronic refractory ITP, insured a remission without side effects. After 2 years of follow-up the patient has not had relapse. A potentially dangerous splenectomy was thus avoided in a phase of the disease in which a spontaneous remission was still very probable.

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“…Another important factor to be considered in relation to the uptake is the retention and binding of the Vinca alkaloids. Working with blood platelets, the main carrier of these alkaloids in blood, Gout et al (1978) have shown that the platelets retain VCR more strongly than VLB. Tubulin is the most likely component binding colchicine and Vinca alkaloids in platelets and other cells (Sabri andOchs, 1973, Castle andCrawford, 1978;Gout et al, 1978).…”

Section: Comparative Uptake Of Vinca Alkaloidsmentioning

confidence: 99%

“…Working with blood platelets, the main carrier of these alkaloids in blood, Gout et al (1978) have shown that the platelets retain VCR more strongly than VLB. Tubulin is the most likely component binding colchicine and Vinca alkaloids in platelets and other cells (Sabri andOchs, 1973, Castle andCrawford, 1978;Gout et al, 1978). When isolated tubulin was studied for its relative binding affinities, the order of binding effectiveness for VCR, VDS, and VLB was 3.9, 1.9, and 1 .O, respectively (Conrad et al, 1979).…”

Section: Comparative Uptake Of Vinca Alkaloidsmentioning

confidence: 99%

Uptake of Vinca Alkaloids into Mammalian Nerve and its Subcellular Components

Iqbal

Ochs

1980

Journal of Neurochemistry

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Three Vinca alkaloids, vinblastine (VLB), vincristine (VCR), and vindesine (VDS), were recently found to affect axoplasmic transport to different degrees, with VCR the most potent. The uptake of these three species by desheathed cat sciatic nerves in vitro was determined by using tritium-labeled derivatives. In a sucrose medium, the uptake of VCR was found to be three to four times greater than that of VLB and VDS, which is in accord with the neurotoxicity of VCR. Uptake of VCR was dependent on Ca2+ concentration in the medium. Removal of Ca2+ from the incubation medium reduced the uptake of VCR, without having much effect on VLB or VDS uptake. The uptake of all three Vinca agents into nerve in a saline medium was about 50% of that in a sucrose medium, and elimination of Ca2+ from the saline incubation medium did not result in any significant change in uptake. High Ca2+ concentrations (100 mM) in the incubation medium, which cause a block of axoplasmic transport, did not change the total uptake of the Vinca alkaloids to any significant degree. The amount of labeled alkaloid found in the soluble fraction was, however, decreased by 50%. There was an increase in the amount present in the particulate fraction, caused, most likely, by an aggregation of vinca-binding components. The amount of VCR associated with tubulin-containing components isolated by gel filtration of the soluble fraction increased twofold when the nerves were exposed to a high-Ca2+ medium, as might be expected of a microtubule disassembly. Exposure of the nerve to low temperatures (0 degrees-4 degrees C) for 90 min did not show any effect on the total uptake of Vinca alkaloids.

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Differences between vinblastine and vincristine in distribution in the blood of rats and binding by platelets and malignant cells

Cited by 33 publications

References 13 publications

Vinblastine and vincristine ‐ growth‐inhibitory effects correlate with their retention by cultured Nb 2 node lymphoma cells

Vinblastine and vincristine ‐ growth‐inhibitory effects correlate with their retention by cultured Nb 2 node lymphoma cells

Infusion of Vincristine-Loaded Platelets in Acute ITP Refractory to Steroids: An Alternative to Splenectomy

Uptake of Vinca Alkaloids into Mammalian Nerve and its Subcellular Components

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