Etoposide toxicity on human neuroblastoma cells in vitro is enhanced by preceeding hyperthermia

Abstract

We demonstrate in vitro that the enhancing effect of increased temperature on the cytotoxicity of etoposide on neuroblastoma cells is not absent, but depends on scheduling. The temperature range used is achievable in total body hyperthermia. Thus, our results are relevant for possible treatment of disseminated neuroblastoma.

Microarray-Analysis: A New Approach to Study the Molecular Mechanisms of Thermo-Chemotherapy

“…We here describe an approach to exploit the power of transcriptional profiling by analyzing the kinetics of gene expression changes in a defined in vitro-model: in the present study, treatment of the human MYCN-amplified neuroblastoma cell line LAN 1 with cisplatin in the presence or absence of hyperthermia was used as a model system for thermochemotherapy in neuroblastoma. A synergism of chemotherapy and hyperthermia has been shown previously in this cell line ( [17] and unpublished data). Here, the kinetic expression profiles of the cellular response to cisplatin, hyperthermia and a combination of both were analyzed to gain new insights into expression patterns and target genes that may underlie the synergism of both treatment modalities.…”

“…Further development of alternative treatment concepts is therefore urgently needed. Since the 1970 s, whole body hyperthermia (WBH) has been used as a promising adjunct therapy to conventional chemo-or radiotherapy for treating certain types of cancer [4], recently being adopted as an experimental strategy for recurrent, advanced stage neuroblastoma as an adjunct to polychemotherapy in vivo and in vitro [9,17,18]. In numerous in vitro studies, hyperthermia has been shown to increase the cytotoxic effects of various antitumoral treatment regimens including alkylants and platinum compounds [5,6].…”

Ifosfamide, carboplatin and etoposide (ICE) as second-line regimen alone and in combination with regional hyperthermia is active in chemo-pre-treated advanced soft tissue sarcoma of adults

“…alkylating agents, platinum compounds and, to a certain degree, etoposide 22,30,31 . Regional hyperthermia (RHT) with concomitant chemotherapy was shown recently to influence local tumour control of STS, while its impact on overall survival remains to be defined in an ongoing phase III trial conducted by the EORTC/ESHO (EORTC 62961/ESHO RHT 95 Study).…”

Role of heat treatment in childhood cancers: Distinct resistance profiles of solid tumor cell lines towards combined thermochemotherapy

“…VP‐16 is known to be an effective anticancer agent in the treatment of several pediatric tumors in clinical application and in in vitro chemosensitivity assays 14,26. But the role of VP‐16 as a thermosensitizer is discussed controversially, some in vitro studies describe that the cytotoxicity of VP‐16 could be enhanced by additional hyperthermia depending on the sequence of application 32,33, whereas others show that the efficacy of VP‐16 was not influenced or even reduced under heat treatment 34,35. Our results suggest that the application of VP‐16 in hyperthermia therapy would only be effective if the tumor cells show high thermosensitivity and if temperatures >43°C during treatment could be achieved.…”