Enhancement of CCNU cytotoxicity by misonidazole: possible therapeutic gain

Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 99%

Chemosensitization by lipophilic nitroimidazoles

Twentyman¹,

Workman²

1983

“…The SCCVII tumour is a squamous carcinoma that arises spontaneously in the abdominal wall of a C3H mouse (Hirst et al, 1982). The SCCVII tumour cell line was thawed from original frozen stocks and maintained by alternate passage in syngeneic mice and cell culture in Eagle's minimum essential medium supplemented with 12.5% fetal bovine serum.…”

mentioning

confidence: 99%

“…The SCCVII tumour cell line was thawed from original frozen stocks and maintained by alternate passage in syngeneic mice and cell culture in Eagle's minimum essential medium supplemented with 12.5% fetal bovine serum. Some of the biological characteristics of the SCCVII tumour were described elsewhere (Hirst et al, 1982). Approximately 1 x 105 SCCVII tumour cells collected from monolayer cultures were inoculated s.c. into the right thigh of the C3H/He male mice both for tumour growth (TG) time assay and for microangiography.…”

mentioning

confidence: 99%

Combined effects of an angiogenesis inhibitor (TNP-470) and hyperthermia

Nishimura

Murata²,

Hiraoka³

1996

Summary TNP-470, a synthetic analogue of fumagillin first isolated from Aspergillus fumigatus, is known to be a potent anti-angiogenic compound. The combined effects on tumour growth and tumour angiogenesis of TNP-470 and hyperthermia were investigated. The tumour used was SCCVII carcinoma of the C3H/He mouse. The tumour response was evaluated by the tumour growth (TG) time assay. The TG time is the time required for one-half of the treated tumours to reach three times the initial tumour volume. Significant delay of tumour growth was observed by TNP-470 alone (100 mg kg-1 x 2 or x 4), indicating that TNP-470 alone has antitumour effect in vivo. When TNP-470 (100 mg kg-1 x 2 or x 4) was administered after hyperthermia at 44°C, the TG times of the combined treatment were significantly longer than those of heat alone (44°C) or TNP-470 (100 mg kg-I x 2 or x 4) alone. However, the TG time of combined treatment with TNP-470 and hyperthermia at 42°C was quite similar to that of TNP-470 alone. This conflicting result on the combined effect of TNP-470 and hyperthermia may be related to the temperature-dependent vascular damage by hyperthermia. Dose-dependent inhibition of angiogenesis by TNP-470 was demonstrated in microangiograms obtained 4 days and 7 days after hyperthermia (44°C for 30 min). It is, thus, suggested that the combined effect of TNP-470 and hyperthermia is attributable to the inhibition of angiogenesis by TNP-470 following heat-induced vascular damage.

“…Mice were killed by cervical dislocation 18-24 h after irradiation. The tumour was removed, weighed and finely chopped with scissors, then disaggregated into a single cell suspension as previously described (Hirst et al, 1982). The cell number was determined using a haemacytometer, and the cell suspension was diluted and plated at the required cell concentration in plastic tissue culture dishes (Becton Dickinson Labware, Oxnard, Ca) with Waymouth's medium plus 15% foetal calf serum.…”

Section: Mice and Tumour Systemsmentioning

confidence: 99%

Cinnarizine and flunarizine as radiation sensitisers in two murine tumours

Wood

Hirst²

1988

Summary The effect of the calcium antagonists, cinnarizine and flunarizine on the radiation sensitivity of two murine tumours, RIF-1 and SCCVII/St was investigated. Initial experiments giving the compounds at 50mgkg-1 i.p. indicated that cinnarizine had no effect on cell survival after 20Gy of X-rays in the RIF-1 sarcoma and only a small effect in the SCCVII/St carcinoma. However, flunarizine produced a small radiosensitisation in the RIF-1 tumour and a substantial sensitisation in the SCCVII/St tumour. Subsequent experiments in the SCCVII/St tumour indicated that the optimal radiosensitising dose of flunarizine was -55mg kg-1, although some sensitisation was apparent throughout the range of 0.05-500mg kg-1. Flunarizine produced a parallel shift in the X-ray dose response curve, equivalent to a 5-fold reduction in hypoxic fraction. In a normal tissue study, 5mgkg-1 flunarizine did not enhance the reduction in white cell counts produced by X-ray doses of 2-8 Gy. These data suggest that flunarizine may have some potential use as a radiosensitiser.Tumour blood flow is considered to be an important determinant in the outcome of treatment by a number of agents, including hyperthermia, chemotherapy and radiation. In the case of hyperthermia, poor tumour blood flow may enhance local heating (Knapp et al., 1985), whereas for chemotherapy, good blood flow to tumours may ensure the drug reaches its target, and for radiation, allow adequate oxygenation essential for effective radiotherapy.Most tumours exhibit a primitive vasculature (Cater et al., 1962), and therefore blood flow to the tumour is dependent to a large extent on the blood supply to the surrounding tissues.A large number of publications have been concerned with the effects of a range of systemically administered vasoactive compounds on the blood flow in tumours (Kruuv et al., 1967;Jirtle et al., 1978;Pallavicini & Hill, 1983), many with conflicting results. The general conclusion to be drawn is that the response is very much dependent upon the tumour system being studied (see Mattson & Peterson, 1981, for review).Nevertheless, alterations in tumour blood flow have recently been used to exploit the properties of certain therapeutic regimens. For example, Chaplin (1986) has found that 5-hydroxytryptamine (5HT) can enhance the effectiveness of the hypoxic cytotoxin, RSU 1069. Similarly Knapp et al. (1986) have used 5HT to enhance tumour response to hyperthermia. In both cases presumably 5HT is acting by decreasing blood flow to the tumour. In contrast, two other vasoactive agents, the calcium antagonists verapamil and flunarizine have been shown to increase tumour blood flow in experimental animals (Kaelin et al., 1982(Kaelin et al., , 1984. This property could therefore be exploited in radiation therapy, where enhanced tumour oxygenation brought about by the increase in tumour blood flow is advantageous.Flunarizine is a unique calcium antagonist in that its vasodilating properties are seen in the peripheral tissues at concentrations which have little effect o...