The Experts below are selected from a list of 39 Experts worldwide ranked by ideXlab platform

John R. Griffiths - One of the best experts on this subject based on the ideXlab platform.

  • effects of nicotinamide and carbogen on tumour oxygenation blood flow energetics and blood glucose levels
    British Journal of Cancer, 2000
    Co-Authors: Simon P Robinson, Franklyn A. Howe, Marion Stubbs, John R. Griffiths
    Abstract:

    Both host carbogen (95% oxygen/5% Carbon Dioxide) Breathing and nicotinamide administration enhance tumour radiotherapeutic response and are being re-evaluated in the clinic. Non-invasive magnetic resonance imaging (MRI) and 31P magnetic resonance spectroscopy (MRS) methods have been used to give information on the effects of nicotinamide alone and in combination with host carbogen Breathing on transplanted rat GH3 prolactinomas. Gradient recalled echo (GRE) MRI, sensitive to blood oxygenation changes, and spin echo (SE) MRI, sensitive to perfusion/flow, showed large signal intensity increases with carbogen Breathing. Nicotinamide, thought to act by suppressing the transient closure of small blood vessels that cause intermittent tumour hypoxia, induced a small increase in blood oxygenation but no detectable change in perfusion/flow. Carbogen combined with nicotinamide was no more effective than carbogen alone. Both carbogen and nicotinamide caused significant increases in the nucleoside triphosphate/inorganic phosphate (βNTP/P i) ratio, implying that the tumour cells normally receive sub-optimal substrate supply, and is consistent with either increased glycolysis and/or a switch to more oxidative metabolism. The most striking observation was the marked increase in blood glucose (twofold) induced by both nicotinamide and carbogen. Whether this may play a role in tumour radiosensitivity has yet to be determined. Copyright 2000 Cancer Research Campaign© 2000 Cancer Research Campaign

  • Response of Hepatoma 9618a and Normal Liver to Host Carbogen and Carbon Monoxide Breathing
    Neoplasia, 1999
    Co-Authors: Simon P Robinson, John R. Griffiths, Loreta M. Rodrigues, Marion Stubbs
    Abstract:

    The effects of hyperoxia (induced by host carbogen [95% oxygen/5% Carbon Dioxide Breathing] and hypoxia (induced by host Carbon monoxide [CO at 660 ppm] Breathing) were compared by using noninvasive magnetic resonance (MR) methods to gain simultaneous information on blood flow/oxygenation and the bioenergetic status of rat Morris H9618a hepatomas. Both carbogen and CO Breathing induced a 1.5- to 2-fold increase in signal intensity in blood oxygenation level dependent (BOLD) MR images. This was due to a decrease in deoxyhemoglobin (deoxyHb), which acts as an endogenous contrast agent, caused either by formation of oxyhemoglobin in the case of carbogen Breathing, or carboxyhemoglobin with CO Breathing. The results were confirmed by observation of similar changes in deoxyHb in arterial blood samples examined ex vivo after carbogen or CO Breathing. There was no change in nucleoside triphosphates (NTP)/Pi in either tumor or liver after CO Breathing, whereas NTP/Pi increased twofold in the hepatoma (but not in the liver) after carbogen Breathing. No changes in tumor intracellular pH were seen after either treatment, whereas extracellular pH became more alkaline after CO Breathing and more acid after carbogen Breathing, respectively. This tumor type and the liver are unaffected by CO Breathing at 660 ppm, which implies an adequate oxygen supply.

  • the effects of host carbogen 95 oxygen 5 Carbon Dioxide Breathing on metabolic characteristics of morris hepatoma 9618a
    British Journal of Cancer, 1998
    Co-Authors: Marion Stubbs, Simon P Robinson, Loreta M. Rodrigues, C S Parkins, David R Collingridge, John R. Griffiths
    Abstract:

    Characteristics of the tumour metabolic profile play a role in both the tumour-host interaction and in resistance to treatment. Because carbogen (95% oxygen/5% Carbon Dioxide) Breathing can both increase sensitivity to radiation and improve chemotherapeutic efficacy, we have studied its effects on the metabolic characteristics of Morris hepatoma 9618a. Host carbogen Breathing increased both arterial blood pCO2 and pO2, but decreased blood pH. A fourfold increase in tumour pO2 (measured polarographically) and a twofold increase in image intensity [measured by gradient recalled echo magnetic resonance (MR) imaging sensitive to changes in oxy/deoxyhaemoglobin] were observed. No changes were seen in blood flow measured by laser Doppler flowmetry. Tumour intracellular pH remained neutral, whereas extracellular pH decreased significantly (P < 0.01). Nucleoside triphosphate/inorganic phosphate (NTP/Pi), tissue and plasma glucose increased twofold and lactate decreased in both intra- and extracellular compartments, suggesting a change to a more oxidative metabolism. The improvement in energy status of the tumour was reflected in changes in tissue ions, including Na+, through ionic equilibria. The findings suggest that the metabolic profile of hepatoma 9618a is defined partly by intrinsic tumour properties caused by transformation and partly by tissue hypoxia, but that it can respond to environmental changes induced by carbogen with implications for improvements in therapeutic efficacy.

  • in vivo detection of ifosfamide by 31p mrs in rat tumours increased uptake and cytotoxicity induced by carbogen Breathing in gh3 prolactinomas
    British Journal of Cancer, 1997
    Co-Authors: Loreta M. Rodrigues, Simon P Robinson, Marion Stubbs, Rj Maxwell, Pmj Mcsheehy, Cr Pinkerton, John R. Griffiths
    Abstract:

    The direct detection and monitoring of anti-cancer drugs in vivo by magnetic resonance spectroscopy (MRS) may lead to improved anti-cancer strategies. 31P-MRS has been used to detect and quantify ifosfamide (IF) in vivo in GH3 prolactinomas and N-methyl-N-nitrosourea (MNU)-induced mammary tumours in rats. The average concentration of IF in the GH3 prolactinoma over the first 2 h following a dose of 250 mg kg-1 i.v. was calculated to be 0.42 micromol g-1 wet weight, with a half-life of elimination (t1/2) of 2-4 h. Carbogen (95% oxygen/5% Carbon Dioxide) Breathing increased the amount of IF taken up by the GH3 prolactinoma by 50% (P<0.01) to 0.68 micromol g-1 wet weight, although t1/2 elimination rates were unchanged. IF was also detected in the liver in vivo, with a t1/2 of about 1 h. Carbogen Breathing did not affect the maximum peak area (Cmax) or the t1/2 in the liver. Most importantly, the carbogen-induced increase in IF uptake by the tumour caused significant growth delay at all time points in the GH3 tumour growth between day 5 and day 12 (P< 0.01) compared with IF alone. These findings show that carbogen Breathing has potential for increasing the efficacy of anti-cancer drugs. Isolated GH3 cells were sensitive to the parent drug (IF) in vitro (IC50 = 1.3 +/- 0.2 mM) suggesting that the GH3 cells may be either expressing P450 enzymes or are sensitive to the parent drug per se.

Marion Stubbs - One of the best experts on this subject based on the ideXlab platform.

  • effects of nicotinamide and carbogen on tumour oxygenation blood flow energetics and blood glucose levels
    British Journal of Cancer, 2000
    Co-Authors: Simon P Robinson, Franklyn A. Howe, Marion Stubbs, John R. Griffiths
    Abstract:

    Both host carbogen (95% oxygen/5% Carbon Dioxide) Breathing and nicotinamide administration enhance tumour radiotherapeutic response and are being re-evaluated in the clinic. Non-invasive magnetic resonance imaging (MRI) and 31P magnetic resonance spectroscopy (MRS) methods have been used to give information on the effects of nicotinamide alone and in combination with host carbogen Breathing on transplanted rat GH3 prolactinomas. Gradient recalled echo (GRE) MRI, sensitive to blood oxygenation changes, and spin echo (SE) MRI, sensitive to perfusion/flow, showed large signal intensity increases with carbogen Breathing. Nicotinamide, thought to act by suppressing the transient closure of small blood vessels that cause intermittent tumour hypoxia, induced a small increase in blood oxygenation but no detectable change in perfusion/flow. Carbogen combined with nicotinamide was no more effective than carbogen alone. Both carbogen and nicotinamide caused significant increases in the nucleoside triphosphate/inorganic phosphate (βNTP/P i) ratio, implying that the tumour cells normally receive sub-optimal substrate supply, and is consistent with either increased glycolysis and/or a switch to more oxidative metabolism. The most striking observation was the marked increase in blood glucose (twofold) induced by both nicotinamide and carbogen. Whether this may play a role in tumour radiosensitivity has yet to be determined. Copyright 2000 Cancer Research Campaign© 2000 Cancer Research Campaign

  • Response of Hepatoma 9618a and Normal Liver to Host Carbogen and Carbon Monoxide Breathing
    Neoplasia, 1999
    Co-Authors: Simon P Robinson, John R. Griffiths, Loreta M. Rodrigues, Marion Stubbs
    Abstract:

    The effects of hyperoxia (induced by host carbogen [95% oxygen/5% Carbon Dioxide Breathing] and hypoxia (induced by host Carbon monoxide [CO at 660 ppm] Breathing) were compared by using noninvasive magnetic resonance (MR) methods to gain simultaneous information on blood flow/oxygenation and the bioenergetic status of rat Morris H9618a hepatomas. Both carbogen and CO Breathing induced a 1.5- to 2-fold increase in signal intensity in blood oxygenation level dependent (BOLD) MR images. This was due to a decrease in deoxyhemoglobin (deoxyHb), which acts as an endogenous contrast agent, caused either by formation of oxyhemoglobin in the case of carbogen Breathing, or carboxyhemoglobin with CO Breathing. The results were confirmed by observation of similar changes in deoxyHb in arterial blood samples examined ex vivo after carbogen or CO Breathing. There was no change in nucleoside triphosphates (NTP)/Pi in either tumor or liver after CO Breathing, whereas NTP/Pi increased twofold in the hepatoma (but not in the liver) after carbogen Breathing. No changes in tumor intracellular pH were seen after either treatment, whereas extracellular pH became more alkaline after CO Breathing and more acid after carbogen Breathing, respectively. This tumor type and the liver are unaffected by CO Breathing at 660 ppm, which implies an adequate oxygen supply.

  • the effects of host carbogen 95 oxygen 5 Carbon Dioxide Breathing on metabolic characteristics of morris hepatoma 9618a
    British Journal of Cancer, 1998
    Co-Authors: Marion Stubbs, Simon P Robinson, Loreta M. Rodrigues, C S Parkins, David R Collingridge, John R. Griffiths
    Abstract:

    Characteristics of the tumour metabolic profile play a role in both the tumour-host interaction and in resistance to treatment. Because carbogen (95% oxygen/5% Carbon Dioxide) Breathing can both increase sensitivity to radiation and improve chemotherapeutic efficacy, we have studied its effects on the metabolic characteristics of Morris hepatoma 9618a. Host carbogen Breathing increased both arterial blood pCO2 and pO2, but decreased blood pH. A fourfold increase in tumour pO2 (measured polarographically) and a twofold increase in image intensity [measured by gradient recalled echo magnetic resonance (MR) imaging sensitive to changes in oxy/deoxyhaemoglobin] were observed. No changes were seen in blood flow measured by laser Doppler flowmetry. Tumour intracellular pH remained neutral, whereas extracellular pH decreased significantly (P < 0.01). Nucleoside triphosphate/inorganic phosphate (NTP/Pi), tissue and plasma glucose increased twofold and lactate decreased in both intra- and extracellular compartments, suggesting a change to a more oxidative metabolism. The improvement in energy status of the tumour was reflected in changes in tissue ions, including Na+, through ionic equilibria. The findings suggest that the metabolic profile of hepatoma 9618a is defined partly by intrinsic tumour properties caused by transformation and partly by tissue hypoxia, but that it can respond to environmental changes induced by carbogen with implications for improvements in therapeutic efficacy.

  • in vivo detection of ifosfamide by 31p mrs in rat tumours increased uptake and cytotoxicity induced by carbogen Breathing in gh3 prolactinomas
    British Journal of Cancer, 1997
    Co-Authors: Loreta M. Rodrigues, Simon P Robinson, Marion Stubbs, Rj Maxwell, Pmj Mcsheehy, Cr Pinkerton, John R. Griffiths
    Abstract:

    The direct detection and monitoring of anti-cancer drugs in vivo by magnetic resonance spectroscopy (MRS) may lead to improved anti-cancer strategies. 31P-MRS has been used to detect and quantify ifosfamide (IF) in vivo in GH3 prolactinomas and N-methyl-N-nitrosourea (MNU)-induced mammary tumours in rats. The average concentration of IF in the GH3 prolactinoma over the first 2 h following a dose of 250 mg kg-1 i.v. was calculated to be 0.42 micromol g-1 wet weight, with a half-life of elimination (t1/2) of 2-4 h. Carbogen (95% oxygen/5% Carbon Dioxide) Breathing increased the amount of IF taken up by the GH3 prolactinoma by 50% (P<0.01) to 0.68 micromol g-1 wet weight, although t1/2 elimination rates were unchanged. IF was also detected in the liver in vivo, with a t1/2 of about 1 h. Carbogen Breathing did not affect the maximum peak area (Cmax) or the t1/2 in the liver. Most importantly, the carbogen-induced increase in IF uptake by the tumour caused significant growth delay at all time points in the GH3 tumour growth between day 5 and day 12 (P< 0.01) compared with IF alone. These findings show that carbogen Breathing has potential for increasing the efficacy of anti-cancer drugs. Isolated GH3 cells were sensitive to the parent drug (IF) in vitro (IC50 = 1.3 +/- 0.2 mM) suggesting that the GH3 cells may be either expressing P450 enzymes or are sensitive to the parent drug per se.

Simon P Robinson - One of the best experts on this subject based on the ideXlab platform.

  • effects of nicotinamide and carbogen on tumour oxygenation blood flow energetics and blood glucose levels
    British Journal of Cancer, 2000
    Co-Authors: Simon P Robinson, Franklyn A. Howe, Marion Stubbs, John R. Griffiths
    Abstract:

    Both host carbogen (95% oxygen/5% Carbon Dioxide) Breathing and nicotinamide administration enhance tumour radiotherapeutic response and are being re-evaluated in the clinic. Non-invasive magnetic resonance imaging (MRI) and 31P magnetic resonance spectroscopy (MRS) methods have been used to give information on the effects of nicotinamide alone and in combination with host carbogen Breathing on transplanted rat GH3 prolactinomas. Gradient recalled echo (GRE) MRI, sensitive to blood oxygenation changes, and spin echo (SE) MRI, sensitive to perfusion/flow, showed large signal intensity increases with carbogen Breathing. Nicotinamide, thought to act by suppressing the transient closure of small blood vessels that cause intermittent tumour hypoxia, induced a small increase in blood oxygenation but no detectable change in perfusion/flow. Carbogen combined with nicotinamide was no more effective than carbogen alone. Both carbogen and nicotinamide caused significant increases in the nucleoside triphosphate/inorganic phosphate (βNTP/P i) ratio, implying that the tumour cells normally receive sub-optimal substrate supply, and is consistent with either increased glycolysis and/or a switch to more oxidative metabolism. The most striking observation was the marked increase in blood glucose (twofold) induced by both nicotinamide and carbogen. Whether this may play a role in tumour radiosensitivity has yet to be determined. Copyright 2000 Cancer Research Campaign© 2000 Cancer Research Campaign

  • Response of Hepatoma 9618a and Normal Liver to Host Carbogen and Carbon Monoxide Breathing
    Neoplasia, 1999
    Co-Authors: Simon P Robinson, John R. Griffiths, Loreta M. Rodrigues, Marion Stubbs
    Abstract:

    The effects of hyperoxia (induced by host carbogen [95% oxygen/5% Carbon Dioxide Breathing] and hypoxia (induced by host Carbon monoxide [CO at 660 ppm] Breathing) were compared by using noninvasive magnetic resonance (MR) methods to gain simultaneous information on blood flow/oxygenation and the bioenergetic status of rat Morris H9618a hepatomas. Both carbogen and CO Breathing induced a 1.5- to 2-fold increase in signal intensity in blood oxygenation level dependent (BOLD) MR images. This was due to a decrease in deoxyhemoglobin (deoxyHb), which acts as an endogenous contrast agent, caused either by formation of oxyhemoglobin in the case of carbogen Breathing, or carboxyhemoglobin with CO Breathing. The results were confirmed by observation of similar changes in deoxyHb in arterial blood samples examined ex vivo after carbogen or CO Breathing. There was no change in nucleoside triphosphates (NTP)/Pi in either tumor or liver after CO Breathing, whereas NTP/Pi increased twofold in the hepatoma (but not in the liver) after carbogen Breathing. No changes in tumor intracellular pH were seen after either treatment, whereas extracellular pH became more alkaline after CO Breathing and more acid after carbogen Breathing, respectively. This tumor type and the liver are unaffected by CO Breathing at 660 ppm, which implies an adequate oxygen supply.

  • the effects of host carbogen 95 oxygen 5 Carbon Dioxide Breathing on metabolic characteristics of morris hepatoma 9618a
    British Journal of Cancer, 1998
    Co-Authors: Marion Stubbs, Simon P Robinson, Loreta M. Rodrigues, C S Parkins, David R Collingridge, John R. Griffiths
    Abstract:

    Characteristics of the tumour metabolic profile play a role in both the tumour-host interaction and in resistance to treatment. Because carbogen (95% oxygen/5% Carbon Dioxide) Breathing can both increase sensitivity to radiation and improve chemotherapeutic efficacy, we have studied its effects on the metabolic characteristics of Morris hepatoma 9618a. Host carbogen Breathing increased both arterial blood pCO2 and pO2, but decreased blood pH. A fourfold increase in tumour pO2 (measured polarographically) and a twofold increase in image intensity [measured by gradient recalled echo magnetic resonance (MR) imaging sensitive to changes in oxy/deoxyhaemoglobin] were observed. No changes were seen in blood flow measured by laser Doppler flowmetry. Tumour intracellular pH remained neutral, whereas extracellular pH decreased significantly (P < 0.01). Nucleoside triphosphate/inorganic phosphate (NTP/Pi), tissue and plasma glucose increased twofold and lactate decreased in both intra- and extracellular compartments, suggesting a change to a more oxidative metabolism. The improvement in energy status of the tumour was reflected in changes in tissue ions, including Na+, through ionic equilibria. The findings suggest that the metabolic profile of hepatoma 9618a is defined partly by intrinsic tumour properties caused by transformation and partly by tissue hypoxia, but that it can respond to environmental changes induced by carbogen with implications for improvements in therapeutic efficacy.

  • in vivo detection of ifosfamide by 31p mrs in rat tumours increased uptake and cytotoxicity induced by carbogen Breathing in gh3 prolactinomas
    British Journal of Cancer, 1997
    Co-Authors: Loreta M. Rodrigues, Simon P Robinson, Marion Stubbs, Rj Maxwell, Pmj Mcsheehy, Cr Pinkerton, John R. Griffiths
    Abstract:

    The direct detection and monitoring of anti-cancer drugs in vivo by magnetic resonance spectroscopy (MRS) may lead to improved anti-cancer strategies. 31P-MRS has been used to detect and quantify ifosfamide (IF) in vivo in GH3 prolactinomas and N-methyl-N-nitrosourea (MNU)-induced mammary tumours in rats. The average concentration of IF in the GH3 prolactinoma over the first 2 h following a dose of 250 mg kg-1 i.v. was calculated to be 0.42 micromol g-1 wet weight, with a half-life of elimination (t1/2) of 2-4 h. Carbogen (95% oxygen/5% Carbon Dioxide) Breathing increased the amount of IF taken up by the GH3 prolactinoma by 50% (P<0.01) to 0.68 micromol g-1 wet weight, although t1/2 elimination rates were unchanged. IF was also detected in the liver in vivo, with a t1/2 of about 1 h. Carbogen Breathing did not affect the maximum peak area (Cmax) or the t1/2 in the liver. Most importantly, the carbogen-induced increase in IF uptake by the tumour caused significant growth delay at all time points in the GH3 tumour growth between day 5 and day 12 (P< 0.01) compared with IF alone. These findings show that carbogen Breathing has potential for increasing the efficacy of anti-cancer drugs. Isolated GH3 cells were sensitive to the parent drug (IF) in vitro (IC50 = 1.3 +/- 0.2 mM) suggesting that the GH3 cells may be either expressing P450 enzymes or are sensitive to the parent drug per se.

Loreta M. Rodrigues - One of the best experts on this subject based on the ideXlab platform.

  • Response of Hepatoma 9618a and Normal Liver to Host Carbogen and Carbon Monoxide Breathing
    Neoplasia, 1999
    Co-Authors: Simon P Robinson, John R. Griffiths, Loreta M. Rodrigues, Marion Stubbs
    Abstract:

    The effects of hyperoxia (induced by host carbogen [95% oxygen/5% Carbon Dioxide Breathing] and hypoxia (induced by host Carbon monoxide [CO at 660 ppm] Breathing) were compared by using noninvasive magnetic resonance (MR) methods to gain simultaneous information on blood flow/oxygenation and the bioenergetic status of rat Morris H9618a hepatomas. Both carbogen and CO Breathing induced a 1.5- to 2-fold increase in signal intensity in blood oxygenation level dependent (BOLD) MR images. This was due to a decrease in deoxyhemoglobin (deoxyHb), which acts as an endogenous contrast agent, caused either by formation of oxyhemoglobin in the case of carbogen Breathing, or carboxyhemoglobin with CO Breathing. The results were confirmed by observation of similar changes in deoxyHb in arterial blood samples examined ex vivo after carbogen or CO Breathing. There was no change in nucleoside triphosphates (NTP)/Pi in either tumor or liver after CO Breathing, whereas NTP/Pi increased twofold in the hepatoma (but not in the liver) after carbogen Breathing. No changes in tumor intracellular pH were seen after either treatment, whereas extracellular pH became more alkaline after CO Breathing and more acid after carbogen Breathing, respectively. This tumor type and the liver are unaffected by CO Breathing at 660 ppm, which implies an adequate oxygen supply.

  • the effects of host carbogen 95 oxygen 5 Carbon Dioxide Breathing on metabolic characteristics of morris hepatoma 9618a
    British Journal of Cancer, 1998
    Co-Authors: Marion Stubbs, Simon P Robinson, Loreta M. Rodrigues, C S Parkins, David R Collingridge, John R. Griffiths
    Abstract:

    Characteristics of the tumour metabolic profile play a role in both the tumour-host interaction and in resistance to treatment. Because carbogen (95% oxygen/5% Carbon Dioxide) Breathing can both increase sensitivity to radiation and improve chemotherapeutic efficacy, we have studied its effects on the metabolic characteristics of Morris hepatoma 9618a. Host carbogen Breathing increased both arterial blood pCO2 and pO2, but decreased blood pH. A fourfold increase in tumour pO2 (measured polarographically) and a twofold increase in image intensity [measured by gradient recalled echo magnetic resonance (MR) imaging sensitive to changes in oxy/deoxyhaemoglobin] were observed. No changes were seen in blood flow measured by laser Doppler flowmetry. Tumour intracellular pH remained neutral, whereas extracellular pH decreased significantly (P < 0.01). Nucleoside triphosphate/inorganic phosphate (NTP/Pi), tissue and plasma glucose increased twofold and lactate decreased in both intra- and extracellular compartments, suggesting a change to a more oxidative metabolism. The improvement in energy status of the tumour was reflected in changes in tissue ions, including Na+, through ionic equilibria. The findings suggest that the metabolic profile of hepatoma 9618a is defined partly by intrinsic tumour properties caused by transformation and partly by tissue hypoxia, but that it can respond to environmental changes induced by carbogen with implications for improvements in therapeutic efficacy.

  • in vivo detection of ifosfamide by 31p mrs in rat tumours increased uptake and cytotoxicity induced by carbogen Breathing in gh3 prolactinomas
    British Journal of Cancer, 1997
    Co-Authors: Loreta M. Rodrigues, Simon P Robinson, Marion Stubbs, Rj Maxwell, Pmj Mcsheehy, Cr Pinkerton, John R. Griffiths
    Abstract:

    The direct detection and monitoring of anti-cancer drugs in vivo by magnetic resonance spectroscopy (MRS) may lead to improved anti-cancer strategies. 31P-MRS has been used to detect and quantify ifosfamide (IF) in vivo in GH3 prolactinomas and N-methyl-N-nitrosourea (MNU)-induced mammary tumours in rats. The average concentration of IF in the GH3 prolactinoma over the first 2 h following a dose of 250 mg kg-1 i.v. was calculated to be 0.42 micromol g-1 wet weight, with a half-life of elimination (t1/2) of 2-4 h. Carbogen (95% oxygen/5% Carbon Dioxide) Breathing increased the amount of IF taken up by the GH3 prolactinoma by 50% (P<0.01) to 0.68 micromol g-1 wet weight, although t1/2 elimination rates were unchanged. IF was also detected in the liver in vivo, with a t1/2 of about 1 h. Carbogen Breathing did not affect the maximum peak area (Cmax) or the t1/2 in the liver. Most importantly, the carbogen-induced increase in IF uptake by the tumour caused significant growth delay at all time points in the GH3 tumour growth between day 5 and day 12 (P< 0.01) compared with IF alone. These findings show that carbogen Breathing has potential for increasing the efficacy of anti-cancer drugs. Isolated GH3 cells were sensitive to the parent drug (IF) in vitro (IC50 = 1.3 +/- 0.2 mM) suggesting that the GH3 cells may be either expressing P450 enzymes or are sensitive to the parent drug per se.

David R Collingridge - One of the best experts on this subject based on the ideXlab platform.

  • the effects of host carbogen 95 oxygen 5 Carbon Dioxide Breathing on metabolic characteristics of morris hepatoma 9618a
    British Journal of Cancer, 1998
    Co-Authors: Marion Stubbs, Simon P Robinson, Loreta M. Rodrigues, C S Parkins, David R Collingridge, John R. Griffiths
    Abstract:

    Characteristics of the tumour metabolic profile play a role in both the tumour-host interaction and in resistance to treatment. Because carbogen (95% oxygen/5% Carbon Dioxide) Breathing can both increase sensitivity to radiation and improve chemotherapeutic efficacy, we have studied its effects on the metabolic characteristics of Morris hepatoma 9618a. Host carbogen Breathing increased both arterial blood pCO2 and pO2, but decreased blood pH. A fourfold increase in tumour pO2 (measured polarographically) and a twofold increase in image intensity [measured by gradient recalled echo magnetic resonance (MR) imaging sensitive to changes in oxy/deoxyhaemoglobin] were observed. No changes were seen in blood flow measured by laser Doppler flowmetry. Tumour intracellular pH remained neutral, whereas extracellular pH decreased significantly (P < 0.01). Nucleoside triphosphate/inorganic phosphate (NTP/Pi), tissue and plasma glucose increased twofold and lactate decreased in both intra- and extracellular compartments, suggesting a change to a more oxidative metabolism. The improvement in energy status of the tumour was reflected in changes in tissue ions, including Na+, through ionic equilibria. The findings suggest that the metabolic profile of hepatoma 9618a is defined partly by intrinsic tumour properties caused by transformation and partly by tissue hypoxia, but that it can respond to environmental changes induced by carbogen with implications for improvements in therapeutic efficacy.