Abstract
Combination therapies of photochemical internalization (PCI) and moderate hyperthermia (MHT) were investigated in an in vitro system consisting of human and rat glioma spheroids. PCI using the amphiphilic photosensitizer, AlPcS2a and two anti cancer agents BLM or 5-FU were used. Spheroids were irradiated with λ = 670 nm laser light in an incubator at temperatures ranging from 37 to 44°C. For each temperature investigated, spheroids were divided into 4 groups: control, drug-only, photodynamic therapy (PDT), and PCI. PDT and PCI spheroids were exposed to radiant exposures ranging from 0.3 to 2.5 J cm(-2) using an irradiance of 5 mW cm(-2). Toxicity was evaluated from spheroid growth kinetics. The combination of PCI and MHT resulted in significant increases in BLM efficacy at 44°C for both cell line derived spheroids compared to controls at 37°C over the range of radiant exposures examined. 5-FU PCI was ineffective for the human cell line at both 37 and 44°C.
Highlights
Despite employing improved surgical techniques and imaging modalities available followed by radiation and chemotherapy, the great majority of glioma patients do suffer a recurrence of their tumors
In addition to oxidative stress, thermal stress responses include the expression of heat shock proteins (HSPs)
There is evidence that oxidative stress levels are potentially damaging to proteins, and the up-regulation of HSPs is required to restore the native structures of these damaged proteins
Summary
Despite employing improved surgical techniques and imaging modalities available followed by radiation and chemotherapy, the great majority of glioma patients do suffer a recurrence of their tumors. Greater than 80% of tumor recurrences occur around the margins of the surgical resection cavity [1, 2]. Chemotherapy has proven effective for the treatment of many tumor types, survival benefits in malignant glioma patients have been modest [3]. In order to improve the effects of conventional therapies, moderate hyperthermia (MHT) has been combined with chemotherapy or ionizing radiation in the treatment of a variety of tumors as adjuvant therapy [4,5,6,7,8]. MHT has been shown to increase the efficacy of a number of cytotoxic drugs [9,10,11]
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