In vitro test-system for chemo- and thermosensitivity: an analysis of survival fractions and cell-cycle distributions in human Ewing's sarcomas as a modelfor tumors in Pediatric Oncology

Abstract

Test-system discloses treatment-specific alterations in tumor cell survival and cell cycle distribution, e. g. synergistic enhancement of cDDP cytotoxicity by heat application, which might predict chemo- and thermosensitivity.

P53-independent thermosensitization by mitomycin c in human non–small-cell lung cancer cells

“…Furthermore, the combined treatment led to a significant reduction of S-phase cells concomitant with an increase in the accumulation of sub-G 1 phase fraction, when G 2 /M arrest was released. These findings were supported by previous reports that mild hyperthermia at 42°C or 43°C induced a G 2 /M arrest in human melanoma and Ewing's sarcoma cells bearing mp53 (37,38). Debes et al (37) reported that simultaneous application of CDDP and hyperthermia at 43°C significantly reduced S-phase cells in human Ewing's sarcoma cell line, which corresponded with the thermal enhancement of CDDP cytotoxicity.…”

“…These findings were supported by previous reports that mild hyperthermia at 42°C or 43°C induced a G 2 /M arrest in human melanoma and Ewing's sarcoma cells bearing mp53 (37,38). Debes et al (37) reported that simultaneous application of CDDP and hyperthermia at 43°C significantly reduced S-phase cells in human Ewing's sarcoma cell line, which corresponded with the thermal enhancement of CDDP cytotoxicity. Therefore, our findings indicate a direct relationship between cell death and the changes in the cell-cycle distribution and aid in understanding of the mechanism for chemical thermoenhancement of cell killing by …”

“…Recent studies have also shown that hyperthermia can lead to changes of cell-cycle distribution, which may be directly related to the heat-induced apoptosis (35)(36)(37). Our data showed that a marked G 2 /M arrest was induced 6 -12 h after mild hyperthermia at 42°C alone in both the neo and the mp53 cells, but not in the wtp53 cells.…”

Killing Effects of Different Physical Factors on Extracorporeal HepG2 Human Hepatoma Cells

“…Though hyperthermia generally facilitates protein and DNA degeneration in cells, anoxic cancer cells were considered to be more sensitive to the hyperthermia than normal organic cells (Debes et al, 2002;Lim et al, 2006;Dayanc et al, 2008). At the molecular biological level, hyperthermia effect catalyses the degeneration of protein in the cell membrane, and in turn reduces cells' self-stability.…”

Personalized primary tumor xenograft model established for the pre-clinical trial to guide postoperative chemotherapy

“…Although in vitro studies (e.g. clonogenic assay [4], MTT [5], ATP-TCA [6], CD-DST [7], histoculture drug response assay (HDRA) [8]) appear to be fairly good for predicting chemosensitivity, they are rarely applied in clinic for ethical reasons [9]. At the same time, positive retrospective clinical correlations have been identified in primary human tumor xenografts in immunocompromised mice [10].…”