ABSTRACT
This article examines environmental illness in athletes. Causes, symptoms, and treatment of heat-related illness, cold-related illness, and altitude-related illness are discussed.
Subject(s)
Environmental Illness/diagnosis , Environmental Illness/therapy , Sports Medicine/methods , Acclimatization , Altitude Sickness/diagnosis , Altitude Sickness/therapy , Body Temperature Regulation/physiology , Dehydration/etiology , Dehydration/prevention & control , Edema/diagnosis , Edema/etiology , Edema/therapy , Environmental Illness/complications , Environmental Illness/physiopathology , Frostbite/diagnosis , Frostbite/therapy , Heat Stress Disorders/complications , Heat Stress Disorders/diagnosis , Heat Stress Disorders/physiopathology , Heat Stress Disorders/therapy , Humans , Hypothermia/diagnosis , Hypothermia/physiopathology , Hypothermia/therapy , Miliaria/diagnosis , Miliaria/therapy , Rewarming/methods , Risk Factors , Sunburn/diagnosis , Sunburn/therapy , Syncope/diagnosis , Syncope/etiology , Syncope/therapy , Tetany/diagnosis , Tetany/etiology , Tetany/therapy , Work Capacity EvaluationABSTRACT
The overexpression of P-glycoprotein (P-gp) causes resistance to chemotherapy in many tumor types. Here, we report intercellular transfer of functional P-gp from P-gp-positive to P-gp-negative cells in vitro and in vivo. The expression of acquired P-gp is transient in isolated cells but persists in the presence of P-gp-positive cells or under the selective pressure of colchicine. The intercellular transfer of functional P-gp occurs between different tumor cell types and results in increased drug resistance both in vitro and in vivo. Most importantly, the acquired resistance permits tumor cells to survive potentially toxic drug concentrations long enough to develop intrinsic P-gp-mediated resistance. P-gp transfer also occurs to putative components of tumor stroma, such as fibroblasts, raising the possibility that multidrug resistance could be conferred by resistant tumor cells to critical stromal elements within the tumor mass. This is the first report, to our knowledge, that a protein transferred between cells retains its function and confers a complex biologic property upon the recipient cell. These findings have important implications for proteomic analyses in tumor samples and resistance to cancer therapy.
Subject(s)
ATP Binding Cassette Transporter, Subfamily B, Member 1/metabolism , Drug Resistance, Multiple , Drug Resistance, Neoplasm , Neuroblastoma/metabolism , ATP Binding Cassette Transporter, Subfamily B, Member 1/genetics , Animals , Cell Line, Tumor , Colchicine/metabolism , Drug Screening Assays, Antitumor , Humans , Mice , Mice, Inbred BALB C , Protein Transport , Recombinant Fusion Proteins/genetics , Recombinant Fusion Proteins/metabolismABSTRACT
PURPOSE: We have previously found that the staurosporine derivative, CGP 41 251, that has a high specificity for inhibiting protein kinase C (PKC), selectively blocks oncogenic ras-p21-induced oocyte maturation and that PKC and jun-N-terminal kinase (JNK), with which oncogenic ras-p21 directly interacts, reciprocally require each other's activation. We sought to determine whether CGP 41 251 blocks proliferation of ras-transformed mammalian cells and whether it synergistically exerts this effect with a ras-p21 peptide (residues 96-110) that interferes with the interaction of ras-p21 with JNK. METHODS: We incubated ras-transformed rat pancreatic cancer TUC-3 cells and their normal counterpart pancreatic acinar BMRPA1 cells with CGP 42 251 alone and in the presence of the ras-p21 96-110 peptide, both in pre- and post-monolayer phases and determined cell counts and morphology and, for TUC-3 cells, their ability to grow on soft agar. In the post-monolayer experiments, we also evaluated these parameters after withdrawal of these agents. RESULTS: CGP 41 251, but not its inactive analogue, CGP 42 700, blocked pre-monolayer growth and reduced post-monolayer cell counts of both TUC-3 and BMRPA1 cells (IC(50) 0.28 and 0.35 micro M, respectively). After 2 weeks of treatment, all the remaining TUC-3 cells exhibited the untransformed phenotype. Withdrawal of CGP 41 251 resulted in almost complete regrowth of the normal BMRPA1 cells while the reverted TUC-3 cells grew much more slowly. These effects were greatly enhanced by the presence of the ras-p21 96-110 peptide. CONCLUSIONS: CGP 41 251 strongly blocks growth of ras-transformed pancreatic cancer cells by causing cell death and by induction of phenotypic reversion. The enhancement of this effect by the ras-p21 96-110 peptide indicated synergy between it and CGP 41 251, allowing it to block proliferation of the transformed cells selectively. These findings suggest the possibility of using these two agents in anticancer therapy.
