Cancer therapies of all forms, radiation, cytotoxic drugs, hyperthermia, etc., have one goal in common. That goal is to eradicate cancer cells. Therefore, when therapies are being tested in the laboratory or applied in the clinic, the ability to which they eradicate the cancer cells needs to be evaluated. Typically, endpoints such as tumor-growth-delay or tumor regression are used, or if intermediate information is desired, invasive tissue samples must be taken. Recently, it has been determined that cells predominantly respond to all forms of treatment of deleterious stimuli in two ways; via programmed cell death (apoptosis) and/or via necrosis.
The aim of this proposal is to test the capability of Electrical Impedance Spectroscopy (EIS) to detect and identify these two forms of cell response via non-invasive, in vivo measurements in solid human xenografts grown in nude mice. Treatment with hyperthermia, with and without verapamil, will be used to induce the different forms of cell response. Then electrical impedance measurements of the tumors will be made during the period between application of the treatment and manifestation of tumor-growth-delay. These EIS measurements will aim to monitor the real-time cellular-level response of the tumor during this period. The work will test the hypotheses: 1. It is possible to make long-term, reliable, repeatable, non-invasive, in vivo Electrical Impedance Spectroscopy (EIS) measurements of the electrical properties of tissues. 2. EIS is capable of detecting and characterizing long-term, hyperthermia-induced, necrotic response sequences during their occurrence, and of discriminating between different characteristics in the necrotic responses caused by different treatments which result in different tumor-growth-delays. 3. EIS is capable of detecting and characterizing the apoptotic cell response sequence within a solid tumor with high apoptotic index, using non-invasive, in vivo measurements. Progress and preliminary data demonstrate the feasibility of measuring cellular-level change with EIS.
| McRae, D A; Esrick, M A; Mueller, S C (1999) Changes in the noninvasive, in vivo electrical impedance of three xenografts during the necrotic cell-response sequence. Int J Radiat Oncol Biol Phys 43:849-57 |
| McRae, D A; Esrick, M A; Mueller, S C (1997) Non-invasive, in-vivo electrical impedance of EMT-6 tumours during hyperthermia: correlation with morphology and tumour-growth-delay. Int J Hyperthermia 13:1-20 |
| Shchepotin, I B; McRae, D A; Shabahang, M et al. (1997) Hyperthermia and verapamil inhibit the growth of human colon cancer xenografts in vivo through apoptosis. Anticancer Res 17:2213-6 |
| McRae, D A; Esrick, M A (1996) Deconvolved electrical impedance spectra track distinct cell morphology changes. IEEE Trans Biomed Eng 43:607-18 |
