By Herbert M. Pinedo, Giuseppe Giaccone, Karol Sikora
The improvement of drug-resistant cancers is taken into account to be the main major quandary to the therapy of melanoma at the present time. approximately half all sufferers with melanoma be afflicted by tumors which are intrinsically proof against chemotherapy, and many of the last part strengthen drug resistance in the course of the process their remedy. This ebook reports the mechanisms and scientific implications of drug resistance in melanoma with unmatched authority. The authors, who're one of the major clinicians and investigators within the box, hide issues of present medical problem, together with a number of drug resistance and its reversal, topoisomerase medicinal drugs, apoptosis, dose depth and escalation, gene treatment and hematopoietic aid.
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Extra info for Drug Resistance in the Treatment of Cancer (Cancer: Clinical Science in Practice)
A. Teicher & E. , 1989). Position in the cell cycle is also critical to the cytotoxic action of some chemotherapeutic agents and is an important variable in the actions of many others (Born, Hug and Trott, 1976; Momparler, 1980). Although a difficult question to approach experimentally (Siemann and Keng, 1988), it is likely that the great proportion of cells that are distal from the vasculature and in a hypoxic and acidotic environment are noncycling. Cells that are noncycling would be expected to be less sensitive to many agents but may be more sensitive to nitrosoureas and bleomycin (Barranco, Novak and Humphrey, 1973; Barranco and Novak, 1974; Twentyman, 1976; Bhuyan, Fraser and Day, 1977).
1990a,b). O6-benzylguanine, which demonstrates greater affinity for the alkyltransferase protein compared with O6-methylguanine, effectively enhances nitrosourea activity both in vitro and in vivo. , 1992) have demonstrated cessation of growth by no tumor regressions using combination therapy with O6-benzylguanine plus a nitrosourea. The results of Friedman et al. 2. Tumor growth delay and regression resulting from treatment of D341 Med and D-456 MG xenografts growing subcutaneous ly in athymic BALB/c mice with BCNU alone or with BCNU plus O6-benzylguanine, O6-methylguanine or streptozocin D341 Med Expt No.
Modulators that act at the level of properties related to the tumor mass include: (1) agents that reverse hypoxic protection and agents that are selectively active under hypoxic conditions and (2) direct inhibitors of extracellular matrix degrading enzymes. Finally, modulators that act by inhibiting the ability of the tumor to mobilize host normal cells include: (1) inhibitors of endothelial cell proliferation such as antiangiogenic and angiostatic agents and (2) inhibitors of intercellular signaling pathways such as cyclooxygenase and lipoxygenase inhibitors.