Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P50583 (asymmetrical)
 12,197 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Focused acoustic shock waves were studied for their effects on human tumor cell viability, clonogenicity, and sensitivity to chemotherapeutic agents. The elastic shock waves used in this investigation were generated with the Dornier HM3-Lithotripter by underwater spark discharge with fixed electrical parameters employing a voltage of 18 kV and a capacitance of 80 nanoFarads. These waves are characterized by a fast varying compression phase, strong asymmetrical pressure and tension phases, and a maximum amplitude of roughly 10(8) Pascal (kg.m-1 s-2). Doses as high as 2000 focused shocks showed little effect on the viability of two different cell lines. There was, however, a dose dependent inhibition of tumor cell proliferation as determined by the growth of clones in soft agarose. Each of the two cell lines showed a unique degree of colony inhibition by shock waves. It was demonstrated that shock wave effects resulted from elastic shock wave interaction with the cells and were not caused by the emission of ultraviolet light coincident with shock wave generation. Shocks were applied at a rate of 100 minute-1 in a 200 l. water bath, thereby removing the possibility for temperature changes during treatments. After treatment with shock waves it was found that tumor cells became more sensitive to growth inhibition by chemotherapeutic agents. Cisplatin, doxorubicin, and 4-hydroperoxycyclophosphamide were each more effective in blocking cell growth after the target cells had been treated with acoustic shocks. Enhanced efficacies ranged from three to 10-fold potentiation of colony inhibition. These results indicate that weak shock waves, which can be focused to a defined target region, may have utility as a cancer treatment modality either alone or in combination with cytotoxic agents.
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PMID:Effect of acoustic shock waves on clonogenic growth and drug sensitivity of human tumor cells in vitro. 279 37

Cisplatin is a widely used anticancer agent that exerts its biological activity principally by damaging DNA. Although detailed knowledge exists concerning mechanisms that lead to cisplatin adducts in DNA, there are few insights into the processes that result in its antitumor action. To explore some of the cellular responses elicited by cisplatin treatment, we studied its influence on DNA supercoiling and DNA gyrase gene expression in E. coli. We found that cisplatin inhibits DNA gyrase in a concentration-dependent manner leading to a transient alteration of DNA supercoiling and to an induction of gyrase gene expression. The induction effect was asymmetrical, affecting gyrB stronger than gyrA. Furthermore, we studied the influence of cisplatin on the supercoiling activity of purified DNA gyrase in vitro and found that cisplatin was an efficient inhibitor of DNA gyrase in the standard assay. However, cisplatin was an excellent inhibitor when added to DNA gyrase before it could interact with its substrate. In this assay GyrB was also more affected by cisplatin than GyrA. This strongly suggests that cisplatin inhibits DNA gyrase primarily by direct interaction with the enzyme. The data from this work present evidence that further cellular responses following cisplatin treatment include DNA gyrase inhibition, altered DNA supercolling and enhanced DNA gyrase gene expression. This suggests an important role of DNA topology in the induction of defense mechanisms against the action of cisplatin in addition to the processes related to DNA damage and repair.
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PMID:The antitumor agent cisplatin inhibits DNA gyrase and preferentially induces gyrB gene expression in Escherichia coli. 896 Mar 74