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This eport examines the association of Mad1p with Bub1p and Bub3p in yeast. These authors found that Mad1p associated significantly better with Bub1p and Bub3p after the spindle checkpoint was activated. In addition, Mad2p and Mps1p, two other heat shock proteins, were also required for this association to occur. Finally, a conserved motif was identified within Mad1p that was shown to be critical for association of Mad1p with Bub1p and Bub3p; mutation of this motif resulted in the loss of the spindle checkpoint.
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Brady D.M., Hardwick K.G. Complex formation between Mad1p, Bub1p, and Bub3p is crucial for spindle checkpoint function. Curr Biol. 10:2000;675-678. This eport examines the association of Mad1p with Bub1p and Bub3p in yeast. These authors found that Mad1p associated significantly better with Bub1p and Bub3p after the spindle checkpoint was activated. In addition, Mad2p and Mps1p, two other heat shock proteins, were also required for this association to occur. Finally, a conserved motif was identified within Mad1p that was shown to be critical for association of Mad1p with Bub1p and Bub3p; mutation of this motif resulted in the loss of the spindle checkpoint.
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Curr Biol
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Brady, D.M.1
Hardwick, K.G.2
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44
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0033594951
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Cdc20 associates with the kinase aurora2/Aik
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This tudy is a seminal step to the understanding of APC regulation by mitotic kinases. Although the authors did not definitively show that AIK regulates cdc20 activity, they did demonstrate cdc20 and AIK co-immunoprecipitation. Furthermore, immunoprecipitates of either AIK or cdc20 both contained kinase activity. This evidence may represent the link between AIK and chromosome separation via the APC.
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Farruggio D.C., Townsley F.M., Ruderman J.V. Cdc20 associates with the kinase aurora2/Aik. Proc Natl Acad Sci USA. 96:1999;7306-7311. This tudy is a seminal step to the understanding of APC regulation by mitotic kinases. Although the authors did not definitively show that AIK regulates cdc20 activity, they did demonstrate cdc20 and AIK co-immunoprecipitation. Furthermore, immunoprecipitates of either AIK or cdc20 both contained kinase activity. This evidence may represent the link between AIK and chromosome separation via the APC.
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(1999)
Proc Natl Acad Sci USA
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Farruggio, D.C.1
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45
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Regulation of the APC and the exit from mitosis
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Morgan D.O. Regulation of the APC and the exit from mitosis. Nat Cell Biol. 1:1999;E47-E53.
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Nat Cell Biol
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Cyclin-like accumulation and loss of the putative kinetochore motor CENP-E results from coupling continuous synthesis with specific degradation at the end of mitosis
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Brown K.D., Coulson R.M., Yen T.J., Cleveland D.W. Cyclin-like accumulation and loss of the putative kinetochore motor CENP-E results from coupling continuous synthesis with specific degradation at the end of mitosis. J Cell Biol. 125:1994;1303-1312.
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The Rab6-binding kinesin, Rab6-KIFL, is required for cytokinesis
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Hill E., Clarke M., Barr F.A. The Rab6-binding kinesin, Rab6-KIFL, is required for cytokinesis. EMBO J. 19:2000;5711-5719.
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Hill, E.1
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50
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0034682707
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The Xenopus chromokinesin Xkid is essential for metaphase chromosome alignment and must be degraded to allow anaphase chromosome movement
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In n elegant series of experiments performed in vitro using Xenopus oocyte extracts, this study nicely demonstrates that Xenopus Kid is a chromosome-associated kinesin that is degraded in anaphase by ubiquitin-mediated proteolysis. The authors further show that depletion of Xenopus Kid results in a defect in prometaphase chromosome alignment, and that an overabundance of Kid can impair anaphase chromosome movement. These findings nicely bracket Kid function in prometaphase, and surely foreshadow similar studies in mammalian cells.
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Funabiki H., Murray A.W. The Xenopus chromokinesin Xkid is essential for metaphase chromosome alignment and must be degraded to allow anaphase chromosome movement. Cell. 102:2000;411-424. In n elegant series of experiments performed in vitro using Xenopus oocyte extracts, this study nicely demonstrates that Xenopus Kid is a chromosome-associated kinesin that is degraded in anaphase by ubiquitin-mediated proteolysis. The authors further show that depletion of Xenopus Kid results in a defect in prometaphase chromosome alignment, and that an overabundance of Kid can impair anaphase chromosome movement. These findings nicely bracket Kid function in prometaphase, and surely foreshadow similar studies in mammalian cells.
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Cell
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Funabiki, H.1
Murray, A.W.2
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51
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The microtubule-dependent motor centromere-associated protein E (CENP-E) is an integral component of kinetochore corona fibers that link centromeres to spindle microtubules
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Yao X., Anderson K.L., Cleveland D.W. The microtubule-dependent motor centromere-associated protein E (CENP-E) is an integral component of kinetochore corona fibers that link centromeres to spindle microtubules. J Cell Biol. 139:1997;435-447.
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J Cell Biol
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Yao, X.1
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52
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CENP-E function at kinetochores is essential for chromosome alignment
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Schaar B.T., Chan G.K., Maddox P., Salmon E.D., Yen T.J. CENP-E function at kinetochores is essential for chromosome alignment. J Cell Biol. 139:1997;1373-1382.
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J Cell Biol
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Schaar, B.T.1
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Maddox, P.3
Salmon, E.D.4
Yen, T.J.5
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53
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0001665802
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CENP-E forms a link between attachment of spindle microtubules to kinetochores and the mitotic checkpoint
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Yao X., Abrieu A., Zheng Y., Sullivan K.F., Cleveland D.W. CENP-E forms a link between attachment of spindle microtubules to kinetochores and the mitotic checkpoint. Nat Cell Biol. 2:2000;484-491.
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Nat Cell Biol
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Yao, X.1
Abrieu, A.2
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Cleveland, D.W.5
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54
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Characterization of the kinetochore binding domain of CENP-E reveals interactions with the kinetochore proteins CENP-F and hBUBR1
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Chan G.K., Schaar B.T., Yen T.J. Characterization of the kinetochore binding domain of CENP-E reveals interactions with the kinetochore proteins CENP-F and hBUBR1. J Cell Biol. 143:1998;49-63.
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Chan, G.K.1
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Yen, T.J.3
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55
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CENP-E as an essential component of the mitotic checkpoint in vitro
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This tudy uses Xenopus oocyte extracts to examine the role of CENP-E in regulation of the metaphase checkpoint. The authors found that immunodepletion of CENP-E prevented cell-cycle arrest induced by the microtubule toxin nocodazole. Furthermore, absence of CENP-E was found to prevent nocodazole-induced binding of Mad2 and Mad1 to kinetochores. An excess of Mad2 could restore nocodazole-induced arrest, despite the absence of CENP-E. The results of this study stand in apparent contrast with those of similar studies in mammalian cells [53]. Both studies reinforce the role of CENP-E as a pivotal player in checkpoint regulation, and the discussion in this paper of the paradoxical findings is informative and thought-provoking.
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Abrieu A., Kahana J.A., Wood K.W., Cleveland D.W. CENP-E as an essential component of the mitotic checkpoint in vitro. Cell. 102:2000;817-826. This tudy uses Xenopus oocyte extracts to examine the role of CENP-E in regulation of the metaphase checkpoint. The authors found that immunodepletion of CENP-E prevented cell-cycle arrest induced by the microtubule toxin nocodazole. Furthermore, absence of CENP-E was found to prevent nocodazole-induced binding of Mad2 and Mad1 to kinetochores. An excess of Mad2 could restore nocodazole-induced arrest, despite the absence of CENP-E. The results of this study stand in apparent contrast with those of similar studies in mammalian cells [53]. Both studies reinforce the role of CENP-E as a pivotal player in checkpoint regulation, and the discussion in this paper of the paradoxical findings is informative and thought-provoking.
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(2000)
Cell
, vol.102
, pp. 817-826
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Abrieu, A.1
Kahana, J.A.2
Wood, K.W.3
Cleveland, D.W.4
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56
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0034631826
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CENP-meta, an essential kinetochore kinesin required for the maintenance of metaphase chromosome alignment in Drosophila
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Yucel J.K., Marszalek J.D., McIntosh J.R., Goldstein L.S., Cleveland D.W., Philp A.V. CENP-meta, an essential kinetochore kinesin required for the maintenance of metaphase chromosome alignment in Drosophila. J Cell Biol. 150:2000;1-11.
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J Cell Biol
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Yucel, J.K.1
Marszalek, J.D.2
McIntosh, J.R.3
Goldstein, L.S.4
Cleveland, D.W.5
Philp, A.V.6
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57
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0032502817
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A marine natural product inhibitor of kinesin motors
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Sakowicz R., Berdelis M.S., Ray K., Blackburn C.L., Hopmann C., Faulkner D.J., Goldstein L.S. A marine natural product inhibitor of kinesin motors. Science. 280:1998;292-295.
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Science
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Sakowicz, R.1
Berdelis, M.S.2
Ray, K.3
Blackburn, C.L.4
Hopmann, C.5
Faulkner, D.J.6
Goldstein, L.S.7
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58
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0033615357
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Small molecule inhibitor of mitotic spindle bipolarity identified in a phenotype-based screen
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This landmark paper describes the identification of a specific inhibitor of the mitotic kinesin Eg5. Using a cell-based screen for antimitotic compounds in a library of ~16 000 small molecules the authors identified several compounds. One of these caused mitotic arrest with a monopolar mitotic spindle, a phenotype previously observed following antibody-mediated disruption of Eg5. The action of this compound, called monasterol, towards Eg5 was confirmed in vitro, although the biochemical mechanism of monasterol action is not described. Monasterol did not affect the activity of kinesin heavy chain. Monasterol is the first inhibitor of a specific kinesin to be identified, and has begun to be utilized as a tool to investigate mitotic spindle function and checkpoint signaling (see annotation to [60••]).
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Mayer T.U., Kapoor T.M., Haggarty S.J., King R.W., Schreiber S.L., Mitchison T.J. Small molecule inhibitor of mitotic spindle bipolarity identified in a phenotype-based screen. Science. 286:1999;971-974. This landmark paper describes the identification of a specific inhibitor of the mitotic kinesin Eg5. Using a cell-based screen for antimitotic compounds in a library of ~16 000 small molecules the authors identified several compounds. One of these caused mitotic arrest with a monopolar mitotic spindle, a phenotype previously observed following antibody-mediated disruption of Eg5. The action of this compound, called monasterol, towards Eg5 was confirmed in vitro, although the biochemical mechanism of monasterol action is not described. Monasterol did not affect the activity of kinesin heavy chain. Monasterol is the first inhibitor of a specific kinesin to be identified, and has begun to be utilized as a tool to investigate mitotic spindle function and checkpoint signaling (see annotation to [60••]).
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(1999)
Science
, vol.286
, pp. 971-974
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Mayer, T.U.1
Kapoor, T.M.2
Haggarty, S.J.3
King, R.W.4
Schreiber, S.L.5
Mitchison, T.J.6
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59
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0029417238
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Phosphorylation by p34cdc2 regulates spindle association of human Eg5, a kinesin-related motor essential for bipolar spindle formation in vivo
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Blangy A., Lane H.A., d'Herin P., Harper M., Kress M., Nigg E.A. Phosphorylation by p34cdc2 regulates spindle association of human Eg5, a kinesin-related motor essential for bipolar spindle formation in vivo. Cell. 83:1995;1159-1169.
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Cell
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Blangy, A.1
Lane, H.A.2
D'Herin, P.3
Harper, M.4
Kress, M.5
Nigg, E.A.6
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60
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0034605123
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Probing spindle assembly mechanisms with monastrol, a small molecule inhibitor of the mitotic kinesin, Eg5
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This study used monasterol to assess the response of the metaphase checkpoint protein Mad2 to mitotic arrest in response to a novel pharmacological antimitotic perturbation. Mad2 was found to localize to kinetochores of bi-oriented chromosomes arrayed on a monopolar mitotic spindle. This observation is directly relevant to the longstanding issue of whether the metaphase checkpoint senses kinetochore attachment or chromosome alignment, and suggests that simple attachment is insufficient to satisfy the checkpoint.
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Kapoor T.M., Mayer T.U., Coughlin M.L., Mitchison T.J. Probing spindle assembly mechanisms with monastrol, a small molecule inhibitor of the mitotic kinesin, Eg5. J Cell Biol. 150:2000;975-988. This study used monasterol to assess the response of the metaphase checkpoint protein Mad2 to mitotic arrest in response to a novel pharmacological antimitotic perturbation. Mad2 was found to localize to kinetochores of bi-oriented chromosomes arrayed on a monopolar mitotic spindle. This observation is directly relevant to the longstanding issue of whether the metaphase checkpoint senses kinetochore attachment or chromosome alignment, and suggests that simple attachment is insufficient to satisfy the checkpoint.
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(2000)
J Cell Biol
, vol.150
, pp. 975-988
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Kapoor, T.M.1
Mayer, T.U.2
Coughlin, M.L.3
Mitchison, T.J.4
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61
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0033576727
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A structural change in the kinesin motor protein that drives motility
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This remarkable study combines several different experimental approaches to demonstrate the substantial structural change in the 'neck' region of kinesin heavy chain that is responsible for force production, directionality and processive movement along microtubules.
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Rice S., Lin A.W., Safer D., Hart C.L., Naber N., Carragher B.O., Cain S.M., Pechatnikova E., Wilson-Kubalek E.M., Whittaker M., et al. A structural change in the kinesin motor protein that drives motility. Nature. 402:1999;778-784. This remarkable study combines several different experimental approaches to demonstrate the substantial structural change in the 'neck' region of kinesin heavy chain that is responsible for force production, directionality and processive movement along microtubules.
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(1999)
Nature
, vol.402
, pp. 778-784
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Rice, S.1
Lin, A.W.2
Safer, D.3
Hart, C.L.4
Naber, N.5
Carragher, B.O.6
Cain, S.M.7
Pechatnikova, E.8
Wilson-Kubalek, E.M.9
Whittaker, M.10
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62
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0034646180
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Inhibitors of kinesin activity from structure-based computer screening
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This study reflects the maturity of kinesin biochemistry, biophysics and structural biology. The authors identify a low micromolar inhibitor of kinesin heavy chain by computational docking of commercially available compounds into its 3-dimensional structure.
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Hopkins S.C., Vale R.D., Kuntz I.D. Inhibitors of kinesin activity from structure-based computer screening. Biochem. 39:2000;2805-2814. This study reflects the maturity of kinesin biochemistry, biophysics and structural biology. The authors identify a low micromolar inhibitor of kinesin heavy chain by computational docking of commercially available compounds into its 3-dimensional structure.
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(2000)
Biochem
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, pp. 2805-2814
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Hopkins, S.C.1
Vale, R.D.2
Kuntz, I.D.3
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Clinical overview of the taxanes
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Goldspiel B.R. Clinical overview of the taxanes. Pharmacotherapy. 17:1997;1105-1255.
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Pharmacotherapy
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Vinorelbine (Navelbine): A third generation vinca alkaloid
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Budman D.R. Vinorelbine (Navelbine): A third generation vinca alkaloid. Cancer Invest. 15:1997;475-490.
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Budman, D.R.1
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