A Comparison of the Physiological Effects of RSU1069 and RB6145 in the SCCVII Murine Tumour

Abstract

The physiological and therapeutic effects of the bioreductive agent RSU1069 (80 mg/kg i.p.) and its prodrug RB6145 (240 mg/kg i.p.) were investigated in the SCCVII tumour. Using laser Doppler flowmetry it was found that RSU1069 produced a significant 30% reduction in tumour blood flow 30 min after administration, while RB6145 had no effect. Tumour oxygenation, measured with an Eppendorf oxygen electrode, was unchanged by either agent except for a reduction in values less than 2.5 mmHg at 30 min after injection. Neither agent significantly altered tumour energy metabolism, assessed by 31P magnetic resonance spectroscopy. Both agents significantly increased tumour glucose content by a factor of 1.6-1.7 at 30 min after injection, but had no effect on glucose-6-phosphate or lactate levels. Tumour growth was significantly delayed by heating (42.5"C, 60 min), and although

Hypoxic Regulation of Glucose Transport, Anaerobic Metabolism and Angiogenesis in Cancer: Novel Pathways and Targets for Anticancer Therapeutics

“…There are several classes of agent in various stages of preclinical and clinical development, the most advanced being tirapazamine (SR 4233) [85,86] , an aromatic benztriazine-di-N-oxide, and AQ4N, an aliphatic N-oxide [87] , in phase III and phase I clinical trials, respectively. New variations on 2-nitroimidazoles, having been investigated thoroughly as radiosensitizers over the years, are now also being studied for their potential as bioreductive cytotoxics [88,89] . The aim of bioreductive drugs is not only to overcome the chemo-and radioresistance caused by hypoxia, but also to exploit this feature by using agents that selectively kill these cells.…”

The Effect of Shark Cartilage Extracts on the Growth and Metastatic Spread of the SCCVII Carcinoma

“…None of the shark cartilage extract doses used in this study had did they influence the metastatic spread of this tumour to the lungs of the host animals. The SCCVII tumour model was selected for this study because it has been well documented, using both in vitro/in vivo excision and tumour growth delay assays, that primary tumours are responsive to conventional anti-cancer therapies such as radiation (19,20), chemotherapeutic drugs (17,18) and hyperthermia (21,22). Growth of this SCCVII tumour has also been shown to be reduced by the anti-angiogenic fumagillin analogue, TNP-470 (22).…”

Application of nano‐radiosensitizers in combination cancer therapy

“…RSU1069 is a well‐known radiosensitizer which acts through electron reduction in hypoxic cells 28 . RB6145 was developed after RSU1069 was found to show gastrointestinal toxicity, and has similar therapeutic effects but is more tolerable 29 . The radiosensitizing effect of both drugs are improved when combined with photodynamic therapy or hyperthermia 29 …”

“… 29 The radiosensitizing effect of both drugs are improved when combined with photodynamic therapy or hyperthermia. 29 …”