Circumvention of multi-drug resistance in human kidney and kidney carcinoma in vitro

Article Abstract:

Drug resistance is a formidable problem for oncologists attempting to use chemotherapy for the treatment of cancer. Some cancers, like colon cancer, are inherently resistant to chemotherapeutic drugs. Other cancers acquire resistance; the cells which grow to form recurrent tumors after chemotherapy are very likely to be resistant to the drug used for the first treatment. Of special interest is the so-called multi-drug resistance. Some cancer cells have resistance to chemotherapeutic agents of many types; this multi-drug resistance seems to result from the presence of a molecular pump that pushes back out any chemotherapeutic agents that might seep into the cell. Presumably, the effectiveness of chemotherapy could be advanced significantly if the cancerous cells could be forced to, in effect, swallow their pills instead of spitting them back out. Using both normal human kidney cells and kidney cancer cells, laboratory investigators have examined the possibility of using the drug trifluoperazine to circumvent multi-drug resistance. Their research demonstrated that it was indeed possible to increase the sensitivity of cells to doxorubicin, a common chemotherapeutic agent, using trifluoperazine. Trifluoperazine is a calmodulin-inhibiting drug that is used in the treatment of psychosis. Calmodulin is a protein that plays a key role in the regulation of calcium within the cell; it is believed that the inhibition of calmodulin results in decreased effectiveness of the P-glycoprotein that makes up the molecular drug pump. Unfortunately, trifluoperazine not only increases the sensitivity of cancer cells to chemotherapy, it increases the sensitivity of normal cells as well. Therefore, any clinical application of such agents to circumvent multi-drug resistance should proceed cautiously until more is learned about how trifluoperazine might also affect the threshold for toxic effects in normal cells. (Consumer Summary produced by Reliance Medical Information, Inc.)

Physiological aspects, Drug resistance, Antipsychotic drugs, Antipsychotic agents, Kidney cancer

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DNA ploidy analysis of effectiveness of radiation therapy for cervical carcinoma

Article Abstract:

Flow cytometry is becoming an increasing common tool used by cancer researchers and clinicians. The device works by dribbling cells past a laser beam and recording the optical properties. By the appropriate choice of fluorescent labelling techniques, a great many cellular properties can be measured, but cancer researchers most commonly use flow cytometry to measure the amount of DNA within cells. A considerable body of evidence has accumulated to suggest that abnormal amounts of DNA indicate a poor prognosis for many, but not all, cancers. Researchers have now attempted to use flow cytometry in a slightly different fashion. Flow cytometry has been used to examine 30 cervical cancers before and after radiation therapy. Prior to radiation therapy, eight of the 30 cancers were diploid or near-diploid. (Normal, healthy cells are diploid, meaning that their chromosomal material is present in pairs.) The remaining 22 tumors were aneuploid, that is, they had an abnormal complement of chromosomes in the cancerous cells. The proportions almost reversed after radiotherapy: 23 tumors were diploid or near-diploid after radiotherapy and only seven were aneuploid. This might suggest that the aneuploid tumors were more sensitive to the radiation, a presumption which seems to be supported by the response data. Complete responses were achieved by 13 of 15 patients whose tumors went from aneuploid to diploid. Only two of the eight patients whose tumors were initially diploid managed to achieve complete responses to radiotherapy. Similarly, of the seven patients with initially aneuploid tumors whose ploidy did not change as a result of the radiotherapy, only two achieved complete responses. These results suggest that there seems to be a correlation between aneuploidy and radiosensitivity in cervical cancers and that aneuploid cancers are likely to respond better to radiotherapy. (Consumer Summary produced by Reliance Medical Information, Inc.)

Usage, Evaluation, Cervical cancer, Genetic aspects, Flow cytometry, Cancer cells

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