Figures & data
Figure 1. Tumour oxygenation as function of MTH and radiation. (A) A single application of MTH (41.5°C; 30 or 60 min) in FSaII murine fibrosarcoma and SCK murine breast carcinoma induces a lasting elevation of median oxygenation up to 48 hours Citation[13]. (B) The extent of reoxygenation diminishes as a function of repeated daily MTH (41.5°C; 60 min) in FSaII tumours. Oxygenation was measured immediately after the treatments. (C) Radiation reduces MTH-induced improved tumour oxygenation. Radiation (3 Gy) reduces the MTH-induced improved tumour oxygenation measured 24 h after the treatments (middle bars), as well as when radiation (3 Gy) is combined with 2 daily MTH (41.5°C; 60 min) treatments and measured immediately after the treatment (bars on the right). The pO2 values of all panels reported are the average of 120 to 700 individual readings derived from 9–15 mice per group per day, with four tracks per mouse and 10 values per track. *p < 0.02, Student's t-test. Tumours were heated by immersing the tumour-bearing legs of anaesthetised mice into preheated water for 60 min, as described previously Citation[54]. The tumour pO2 was measured with an Eppendorf pO2 Histograph (Hamburg, Germany). Tumour-bearing animals were laid on a Plexiglas board and the tumour-bearing legs were gently stretched and affixed by taping the foot to the board. A pO2 electrode (300 µm diameter, Eppendorf) was inserted by hand into the tumours through small incisions made in the skin over the distal side of the tumour. The electrode was then advanced by a computer-controlled system measuring pO2 along the track: the electrode was advanced by 0.7 mm forward steps, immediately withdrawn by 0.3 mm to reduce the compression pressure and the pO2 value was recorded Citation[50], Citation[38–43]. Tumours were locally irradiated with a Philips 250 Kv X-ray machine at a dose rate of 1.4 Gy/min. The body was shielded with lead and only the tumour and foot exposed to the X-ray beam, as described earlier Citation[58].
![Figure 1. Tumour oxygenation as function of MTH and radiation. (A) A single application of MTH (41.5°C; 30 or 60 min) in FSaII murine fibrosarcoma and SCK murine breast carcinoma induces a lasting elevation of median oxygenation up to 48 hours Citation[13]. (B) The extent of reoxygenation diminishes as a function of repeated daily MTH (41.5°C; 60 min) in FSaII tumours. Oxygenation was measured immediately after the treatments. (C) Radiation reduces MTH-induced improved tumour oxygenation. Radiation (3 Gy) reduces the MTH-induced improved tumour oxygenation measured 24 h after the treatments (middle bars), as well as when radiation (3 Gy) is combined with 2 daily MTH (41.5°C; 60 min) treatments and measured immediately after the treatment (bars on the right). The pO2 values of all panels reported are the average of 120 to 700 individual readings derived from 9–15 mice per group per day, with four tracks per mouse and 10 values per track. *p < 0.02, Student's t-test. Tumours were heated by immersing the tumour-bearing legs of anaesthetised mice into preheated water for 60 min, as described previously Citation[54]. The tumour pO2 was measured with an Eppendorf pO2 Histograph (Hamburg, Germany). Tumour-bearing animals were laid on a Plexiglas board and the tumour-bearing legs were gently stretched and affixed by taping the foot to the board. A pO2 electrode (300 µm diameter, Eppendorf) was inserted by hand into the tumours through small incisions made in the skin over the distal side of the tumour. The electrode was then advanced by a computer-controlled system measuring pO2 along the track: the electrode was advanced by 0.7 mm forward steps, immediately withdrawn by 0.3 mm to reduce the compression pressure and the pO2 value was recorded Citation[50], Citation[38–43]. Tumours were locally irradiated with a Philips 250 Kv X-ray machine at a dose rate of 1.4 Gy/min. The body was shielded with lead and only the tumour and foot exposed to the X-ray beam, as described earlier Citation[58].](/cms/asset/8c2a25b4-e62b-4cd6-a0e4-3e3fda4b7cff/ihyt_a_445715_f0001_b.gif)
Figure 2. The effect of MTH on FSaII tumour growth delay by radiation. (A) Daily exposures of radiation (3 Gy) and MTH (41.5°C; 60 min) for 7 consecutive days (schedule q1dx7) increased FSaII tumour growth delay to a modest extent compared to radiation alone. -▪- control; -•- MTH (41.5°C; 60 min.; q1dx7); -▾- radiation (3 Gy; q1dx7); -◂- radiation prior to MTH; -▸- MTH prior to radiation. Data points represent the means (n = 10 animals per group) ± SEM. Arrows indicate treatment schedule. (B) MTH (41.5°C; 60 min) applied every other day prior to daily irradiation (3 GY) increased FSaII tumour growth delay as compared to MTH given post radiation. -▪- control; -•- MTH (41.5°C; 60 min; q2dx4); -◂- radiation (3 Gy; q1dx7) prior to MTH; -▸- MTH prior to radiation. Data points represent the means (n = 9–10 animals per group) ± SEM. (C) MTH applied every other day before accelerated radiation therapy significantly improves tumour response to radiotherapy. -▪- control; -•- MTH (41.5°C; 60 min; q2dx3); -▾- radiation (daily 2 × 2 Gy with 6-h interval); -▸- MTH prior to radiation. Data points represent the means (n = 8–10 animals per group) ±SEM. Arrows alone indicate radiation schedule; arrows with a box-shaped addition indicate MTH and radiation treatment. The FSaII tumours were grown and handled as described earlier Citation[13], with the slight modification that the mice were randomised and treatments were initiated when tumours reached at least an average of 200 mm3 in size. Tumour volume was measured with a caliper (Scienceware) and calculated according the equation: (a2× b) /2, where a is the width and b the length of the tumour Citation[59]. Tumours were heated by immersing the tumour-bearing legs of anaesthetised mice into preheated water for 60 min, as described previously Citation[54]. Tumours were locally irradiated with a Philips 250 Kv X-ray machine at a dose rate of 1.4 Gy/min. The body was shielded with lead and only the tumour and foot exposed to the X-ray beam, as described earlier Citation[58].
![Figure 2. The effect of MTH on FSaII tumour growth delay by radiation. (A) Daily exposures of radiation (3 Gy) and MTH (41.5°C; 60 min) for 7 consecutive days (schedule q1dx7) increased FSaII tumour growth delay to a modest extent compared to radiation alone. -▪- control; -•- MTH (41.5°C; 60 min.; q1dx7); -▾- radiation (3 Gy; q1dx7); -◂- radiation prior to MTH; -▸- MTH prior to radiation. Data points represent the means (n = 10 animals per group) ± SEM. Arrows indicate treatment schedule. (B) MTH (41.5°C; 60 min) applied every other day prior to daily irradiation (3 GY) increased FSaII tumour growth delay as compared to MTH given post radiation. -▪- control; -•- MTH (41.5°C; 60 min; q2dx4); -◂- radiation (3 Gy; q1dx7) prior to MTH; -▸- MTH prior to radiation. Data points represent the means (n = 9–10 animals per group) ± SEM. (C) MTH applied every other day before accelerated radiation therapy significantly improves tumour response to radiotherapy. -▪- control; -•- MTH (41.5°C; 60 min; q2dx3); -▾- radiation (daily 2 × 2 Gy with 6-h interval); -▸- MTH prior to radiation. Data points represent the means (n = 8–10 animals per group) ±SEM. Arrows alone indicate radiation schedule; arrows with a box-shaped addition indicate MTH and radiation treatment. The FSaII tumours were grown and handled as described earlier Citation[13], with the slight modification that the mice were randomised and treatments were initiated when tumours reached at least an average of 200 mm3 in size. Tumour volume was measured with a caliper (Scienceware) and calculated according the equation: (a2× b) /2, where a is the width and b the length of the tumour Citation[59]. Tumours were heated by immersing the tumour-bearing legs of anaesthetised mice into preheated water for 60 min, as described previously Citation[54]. Tumours were locally irradiated with a Philips 250 Kv X-ray machine at a dose rate of 1.4 Gy/min. The body was shielded with lead and only the tumour and foot exposed to the X-ray beam, as described earlier Citation[58].](/cms/asset/1b992270-f4e4-4908-b4f8-f3911c56e2d1/ihyt_a_445715_f0002_b.gif)