Platinum and Other Metal Coordination Compounds in Cancer Chemotherapy, Том 1

Передня обкладинка
Stephen B. Howell
Springer Science & Business Media, 1991 - 545 стор.
Taken together the data presented in this review, and work by many other investigators, support the notion that DNA excision repair is important in a tumor cell's resistance to platinum compounds. Inhibition of this repair system by combination chemotherapy with the excision repair inhibitors HU and Ara-C produces synergistic cell kills and increased levels and persistance of DNA interstrand crosslinks. The studies with cis-DDP and ~-DDP in combination with UV induced thymine dimers suggest that there may be competition for DNA repair enzymes between the dimer and the platinum lesion. Whether the competing lesion is an intrastrand crosslink, interstrand crosslink, or platinum monoadduct (or all of these lesions) cannot be determined. The similarity between an intrastrand crosslink and a cyclobutane dimer suggests that these lesions may compete for repair. However, the increased peak levels of interstrand crosslinks, and increased persistence of these lesions at later time points suggest that this lesion may also be a substrate for the repair system. These observations may be of clinical relevance. Recently Dr. Kathy Albain of our institution has completed a Phase III I study using a 12 hour pretreatment with HU and Ara-C in patients prior to their cis-DDP therapy. She observed a significant number of responders in this trial (54). She is currently completing a second Phase IIII study substituting IV HU for the oral formulation. We anticipate initiating other clinical trials based upon these observations.
 

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I
1
II
13
III
25
IV
37
V
51
VI
61
VII
73
VIII
81
XXVIII
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XXIX
315
XXX
323
XXXI
335
XXXII
345
XXXIII
357
XXXIV
369
XXXV
377

IX
93
X
101
XI
115
XII
127
XIII
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XIV
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XV
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XVI
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XVII
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XVIII
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XIX
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XX
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XXI
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XXII
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XXIII
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XXIV
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XXV
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XXVI
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XXVII
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XXXVI
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XXXVII
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XXXVIII
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XXXIX
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XL
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XLI
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XLII
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XLIII
459
XLIV
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XLV
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XLVI
481
XLVII
493
XLVIII
501
XLIX
509
L
517
LI
529
LII
541
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