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2019 - High content in vitro cell monitoring effects of adjuvant chemotherapy in breast cancer and cancer treatment-related cardiomyopathy

Icon CE   CardioExcyte 96 poster, SOT Conference 2019  logo pdf   (0.8 MB)

Abstract:

Impedance changes of cell-covered electrodes give profound insight into cell proliferation and contractility, even over prolonged time periods, providing significant advantage over standard mostly endpoint cytotoxicity assays. Here, this technology was used for monitoring cell regrowth in breast cancer, after chemotherapy treatment in vitro. As the emerging field of cardio-oncology aims to find a balance between oncologic efficacy and reducing adverse cardiovascular effects, we tested the same treatment on induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs). One of the standard clinical regimens for breast cancer is a combination of cyclophosphamide, adriamycin (doxorubicin) and 5-fluorouracil (CAF) administered for 4 months. Even though initially successful, tumor recurrence after this therapy remains a major cause of mortality in breast cancer patients, leaving the need for better treatment.
We investigated responses from murine H8N8 (immortal mammary carcinoma cell line with tumor stem cell properties) and H8N8 T3.2 (once-treated recurrent tumor variant) cells, by using impedance monitoring compared to image-based analysis. For in vitro tumor regrowth investigation, H8N8 T3.2 cells were treated with CAF for a second time. Changes in impedance and confluency of these cells, were used as a measure of toxicity with cell viability monitored for 500h, under physiological conditions. Intrinsic (dose-dependent) effects of CAF clinical treatment; dose- and treatment cycle-dependent regrowth of tumor cells was observed. We further investigated putative cardiovascular side effects of CAF mix and paclitaxel and their long-and short-term implications on iPSC-CMs viability. Our results show a dose dependent negative effect of paclitaxel on the viability of iPSC-CMs, as seen in the base impedance reduction. This was also observed for doxorubicin alone, but not the rest of the CAF compound mix. Paclitaxel and CAF also induced negative changes in cell contraction properties.
In summary, long-term high-resolution impedance monitoring provides amenable insights into dynamics of cell proliferation and contraction, for in vitro investigations of adjuvant chemotherapy not only in cancer but in cardiac-oncology field.

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