The Vinca Alkaloids

Neuss, Norbert; Johnson, Irving S.; Armstrong, James G.; Jansen, Christian J.

doi:10.1016/b978-1-4831-9929-0.50010-3

Cited by 21 publications

(10 citation statements)

References 31 publications

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“…The present results indicate that mitosis inhibitors are capable of influencing blood platelet function and confirm and extend some of the observations made by White (1968bWhite ( , 1969b, c) on human platelets. The concentrations of the drugs used in the present study are similar to those reported for experiments on human platelets (White, 1968b;Behnke, 1970), but are higher than those required to influence other cellular systems (for example, see Neuss, Johnson & Armstrong 1964;Bensch & Malawista, 1968;Margulis, Banerjee & White,1969). The reason that such relatively high concentrations of mitosis inhibitors are required in the present study is not immediately apparent.…”

Section: Discussionsupporting

confidence: 82%

“…Colchicine also collapses cystoskeletal structures in protozoa (Tilney, 1968), and prevents intra-axonal transport in peripheral nerves (Dahlstr6m, 1968;Kreutzberg, 1969). These diverse actions are believed to be the result of the ability of these drugs to depolymerize cytoplasmic microtubules (for reference see Neuss, Johnson & Armstrong, 1964;Schmitt, 1968;Wisniewski, Shelanski & Terry, 1968), and it is suggested that these and other cellular functions are intimately 152 PLATELET MICROTUBULES AND AGGREGATION 153 associated with the integrity of the microtubules. Colchicine (Borisy & Taylor, 1967), colcemid (Zimmerman & Zimmerman, 1967), and vinblastine (Bensch & Malawista, 1968;Marantz, Ventilla & Shelanski, 1969) have been shown to have high binding coefficients for microtubular protein, and a colchicine-binding protein with acetin-like properties has recently been isolated from human blood platelets (Puszkin, Aledort & Puszkin, 1969).…”

Section: Discussionmentioning

confidence: 99%

“…&Armstrong, 1964;Schmitt, 1968;Wisniewski, Shelanski & Terry, 1968), and it is suggested that these and other cellular functions are intimately…”

mentioning

confidence: 99%

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Effect of mitosis inhibitors on blood platelet microtubules and aggregation

Sneddon¹

1971

The Journal of Physiology

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1. An inhibitory action of the mitosis inhibitors colchicine, colcemid and vinblastine on blood platelet aggregation has been demonstrated. 2. The inhibitory action of low concentrations of these drugs was surmountable by increasing the concentration of the aggregating agents adenosine diphosphate (ADP) or thrombin. High concentrations completely inhibited aggregation. 3. The presence of a circumferential bundle of microtubules has been demonstrated in rabbit platelets. 4. After exposure to aggregating doses of ADP and thrombin the microtubules move to the centre of the cell, ‘trapping’ the platelet intracellular organelles in a relatively clear cytoplasm. 5. Concentrations of the antimitotic agents which reduce platelet aggregation depolymerize the platelet microtubules and prevent the rearrangement of the platelet organelles during aggregation. 6. It is suggested that the microtubules are not essential for platelet aggregation but are intimately involved in the movement of intracellular granules. This may be a preliminary stage in the eventual discharge of the granules during the platelet ‘release reaction’.

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Section: Discussionsupporting

confidence: 82%

Section: Discussionmentioning

confidence: 99%

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Effect of mitosis inhibitors on blood platelet microtubules and aggregation

Sneddon¹

1971

The Journal of Physiology

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“…6A). These results indicate that ALL-MSCs do not show a propensity to undergo malignant transformation when forced in our ex vivo culture system, even after being exposed to repeated doses of vincristine, daunorubicine, cytosine-arabinoside, cyclophosphamide, 6-mercaptopurine and methotrexate, drugs which are known to induce DNA synthesis block and damage [34], [35].…”

Section: Resultsmentioning

confidence: 99%

Biological, Functional and Genetic Characterization of Bone Marrow-Derived Mesenchymal Stromal Cells from Pediatric Patients Affected by Acute Lymphoblastic Leukemia

et al. 2013

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Alterations in hematopoietic microenvironment of acute lymphoblastic leukemia patients have been claimed to occur, but little is known about the components of marrow stroma in these patients. In this study, we characterized mesenchymal stromal cells (MSCs) isolated from bone marrow (BM) of 45 pediatric patients with acute lymphoblastic leukemia (ALL-MSCs) at diagnosis (day+0) and during chemotherapy treatment (days: +15; +33; +78), the time points being chosen according to the schedule of BM aspirates required by the AIEOP-BFM ALL 2009 treatment protocol. Morphology, proliferative capacity, immunophenotype, differentiation potential, immunomodulatory properties and ability to support long-term hematopoiesis of ALL-MSCs were analysed and compared with those from 41 healthy donors (HD-MSCs). ALL-MSCs were also genetically characterized through array-CGH, conventional karyotyping and FISH analysis. Moreover, we compared ALL-MSCs generated at day+0 with those isolated during chemotherapy. Morphology, immunophenotype, differentiation potential and in vitro life-span did not differ between ALL-MSCs and HD-MSCs. ALL-MSCs showed significantly lower proliferative capacity (p<0.001) and ability to support in vitro hematopoiesis (p = 0.04) as compared with HD-MSCs, while they had similar capacity to inhibit in vitro mitogen-induced T-cell proliferation (p = N.S.). ALL-MSCs showed neither the typical translocations carried by the leukemic clone (when present), nor other genetic abnormalities acquired during ex vivo culture. Our findings indicate that ALL-MSCs display reduced ability to proliferate and to support long-term hematopoiesis in vitro. ALL-MSCs isolated at diagnosis do not differ from those obtained during treatment.

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“…Ketalization and reduction with lithium aluminum hydride followed by deketalization proceeded in high overall yield to complete the preparation of tricyclic amino ketone 4. With amino ketone 4 in hand, one was ready to perform the crucial Fischer indole synthesis. It is worthy of note that, although 4 possesses the all-cis configuration necessary to produce a pentacyclic alkaloid precursor having the same relative stereochemical relationships as those present in aspidospermine and related natural products, the three configurational isomers of 4 should also lead to this same final stereochemistry. Stork pointed out that the indolenine 25 formed during the Fischer indole cyclization was generated under conditions which would lead to equilibration at the two centers marked by asterisks via a reverse Mannich reaction.2 This equilibration proceeds through t the open form 26, which can conceivably reclose to give any of the possible stereoisomers.…”

Section: Ch=ch-ch2nh2mentioning

confidence: 99%