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Chemical Compound Review

Carbogen     carbon dioxide; molecular oxygen

Synonyms: UN1014, LS-186705, AC1L1XL2, 8063-77-2, Carbon dioxide, mixt. with oxygen
 
 
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Disease relevance of UN1014

  • Both the nitroimidazole drugs and hyperthermia produced additional tumor growth delays and tumor cell cytotoxicity when given with Fluosol-DA/carbogen, either before or after irradiation [1].
  • Thus the enhancement in antitumor activity produced by the addition of Fluosol-DA and carbogen breathing to etoposide treatment was not accompanied by a concomitant increase in normal tissue toxicity and represents an increase in the therapeutic efficacy of etoposide [2].
  • Modification of photodynamic therapy-induced hypoxia by fluosol-DA (20%) and carbogen breathing in mice [3].
  • In vivo studies exhibited excellent correlation between carbogen-induced changes in SO(2) and pO(2) of radiation-induced fibrosarcoma tumors measured by reflectance spectroscopy and the Eppendorf pO(2) histograph, respectively [4].
  • Tumor biopsies were obtained from patients with head and neck carcinomas that were potential candidates for a Phase II trial with accelerated radiotherapy combined with carbogen and nicotinamide (ARCON) [5].
 

Psychiatry related information on UN1014

 

High impact information on UN1014

  • Fluosol-DA and carbogen breathing did not increase the toxicity of etoposide to the bone marrow [2].
  • 3. With the use of both single-dose and multiple-dose protocols for etoposide and Fluosol-DA with air or carbogen breathing, the survival of bone marrow cells was measured by colony formation in vitro (granulocyte-monocyte colony-forming units) [2].
  • We conclude that carbogen breathing can increase tumor uptake of 5FU by two independent mechanisms involving changes in tumor blood flow and pH, which consequently cause increased formation of 5-fluoronucleotides and cytotoxicity [7].
  • We propose that carbogen may transiently open nonfunctional blood vessels in the tumor, allowing increased leakage of 5FU from the plasma into the extracellular space [7].
  • On breathing carbogen, patients pretreated with nicotinamide showed an increase in tumor perfusion of 17% at 5 min and 22% at 10 min, compared with only 0% and 1% in the control group [8].
 

Chemical compound and disease context of UN1014

  • Modulation of alkylating agents by etanidazole and Fluosol-DA/carbogen in the FSaIIC fibrosarcoma and EMT6 mammary carcinoma [9].
  • We have examined the effects of a wide range of levels of Therox, a perfluorochemical emulsion containing bis-perfluorobutyl ethylene (F44E) with carbogen breathing on the tumor growth delay of the Lewis lung carcinoma produced by single dose radiation and fractionated radiation [10].
  • CONCLUSION: Nicotinamide and carbogen administration can increase 5-FU delivery to colorectal cancer liver metastases [11].
  • Hypoxia, defined as the percent of pO2 readings < or = 5 mm Hg, was decreased from 71% in untreated air-breathing controls to 34% in animals treated with the anti-angiogenic agents, the perflubron emulsion and carbogen breathing [12].
  • METHODS AND MATERIALS: Previously we have shown that a double bioreductive hypoxic marker assay could be used to detect changes of tumor hypoxia in relation to the tumor vasculature after carbogen and hydralazine treatments [13].
 

Biological context of UN1014

 

Anatomical context of UN1014

 

Associations of UN1014 with other chemical compounds

  • The administration of a perfluorochemical emulsion and carbogen (95% O2, 5% CO2) breathing before photodynamic therapy (PDT) was studied to determine how increased levels of tumor oxygenation may affect PDT-induced tumor destruction [3].
  • We determined FSaII tumor regrowth delay after isosorbide dinitrate administration and irradiation compared to carbogen breathing before irradiation and with X-rays alone [22].
  • METHODS: Retinal oxygenation (DeltaPO2) was measured by MRI before (room air [ra]) and during a 4-minute carbogen inhalation challenge in five groups: control Sprague-Dawley (SD) and Lewis (LEW) rats, 3- to 4-month diabetic SD and LEW rats, and 4-month diabetic LEW rats preventatively treated with a chow LPA admix (400 mg/kg per chow) [23].
  • Retinal oxygenation (DeltaPo(2)), an established early surrogate marker of drug treatment efficacy, was measured by MRI during a 2-minute carbogen inhalation challenge in four groups: control rats (n = 7), control rats treated with bosentan (n = 7), 3-month diabetic rats (n = 9), and 3-month diabetic rats treated with bosentan (n = 5) [24].
  • Hypoxic radiosensitizers in radical radiotherapy for patients with bladder carcinoma: hyperbaric oxygen, misonidazole, and accelerated radiotherapy, carbogen and nicotinamide [25].
 

Gene context of UN1014

  • At P26 and P34, in 50/10 rats that no longer had NV, retinal deltaPO(2)s during carbogen breathing were significantly (P < 0.05) lower than that of age-matched control pups [26].
  • Retinal DeltaPO(2) during carbogen breathing was also measured in PKCbeta knockout (C57BL6-Prkcb1; [KO]), 4 month C57BL/6J diabetic (D), and 4-month diabetic PKCbeta KO (D+KO) mice [27].
  • Carbogen breathing for 5 min increased the SCK tumor pO2 to 17.1 +/- 1.4 mm Hg [28].
  • In 12 out of 17 patients studied there was a significant increase in median tumour p02 during the first 10 min of carbogen breathing (range 9 to 1800%) [29].
  • Hyperfractionated chemoradiation with carbogen breathing, with or without erythropoietin: a stepwise developed treatment schedule for advanced head-and-neck cancer [30].
 

Analytical, diagnostic and therapeutic context of UN1014

References

  1. Addition of misonidazole, etanidazole, or hyperthermia to treatment with fluosol-DA/carbogen/radiation. Teicher, B.A., Herman, T.S., Holden, S.A., Jones, S.M. J. Natl. Cancer Inst. (1989) [Pubmed]
  2. Effect of oxygen on the cytotoxicity and antitumor activity of etoposide. Teicher, B.A., Holden, S.A., Rose, C.M. J. Natl. Cancer Inst. (1985) [Pubmed]
  3. Modification of photodynamic therapy-induced hypoxia by fluosol-DA (20%) and carbogen breathing in mice. Fingar, V.H., Mang, T.S., Henderson, B.W. Cancer Res. (1988) [Pubmed]
  4. Treatment-induced changes in tumor oxygenation predict photodynamic therapy outcome. Wang, H.W., Putt, M.E., Emanuele, M.J., Shin, D.B., Glatstein, E., Yodh, A.G., Busch, T.M. Cancer Res. (2004) [Pubmed]
  5. Pimonidazole binding and tumor vascularity predict for treatment outcome in head and neck cancer. Kaanders, J.H., Wijffels, K.I., Marres, H.A., Ljungkvist, A.S., Pop, L.A., van den Hoogen, F.J., de Wilde, P.C., Bussink, J., Raleigh, J.A., van der Kogel, A.J. Cancer Res. (2002) [Pubmed]
  6. Management of a severe forceful breather with Rett Syndrome using carbogen. Smeets, E.E., Julu, P.O., van Waardenburg, D., Engerstr??m, I.W., Hansen, S., Apartopoulos, F., Curfs, L.M., Schrander-Stumpel, C.T. Brain Dev. (2006) [Pubmed]
  7. Carbogen breathing increases 5-fluorouracil uptake and cytotoxicity in hypoxic murine RIF-1 tumors: a magnetic resonance study in vivo. McSheehy, P.M., Robinson, S.P., Ojugo, A.S., Aboagye, E.O., Cannell, M.B., Leach, M.O., Judson, I.R., Griffiths, J.R. Cancer Res. (1998) [Pubmed]
  8. Human tumor blood flow is enhanced by nicotinamide and carbogen breathing. Powell, M.E., Hill, S.A., Saunders, M.I., Hoskin, P.J., Chaplin, D.J. Cancer Res. (1997) [Pubmed]
  9. Modulation of alkylating agents by etanidazole and Fluosol-DA/carbogen in the FSaIIC fibrosarcoma and EMT6 mammary carcinoma. Teicher, B.A., Herman, T.S., Tanaka, J., Eder, J.P., Holden, S.A., Bubley, G., Coleman, C.N., Frei, E. Cancer Res. (1991) [Pubmed]
  10. Optimization of perfluorochemical levels with radiation therapy in mice. Teicher, B.A., Herman, T.S., Jones, S.M. Cancer Res. (1989) [Pubmed]
  11. Carbogen and nicotinamide increase blood flow and 5-fluorouracil delivery but not 5-fluorouracil retention in colorectal cancer metastases in patients. Gupta, N., Saleem, A., Kötz, B., Osman, S., Aboagye, E.O., Phillips, R., Vernon, C., Wasan, H., Jones, T., Hoskin, P.J., Price, P.M. Clin. Cancer Res. (2006) [Pubmed]
  12. Influence of an anti-angiogenic treatment on 9L gliosarcoma: oxygenation and response to cytotoxic therapy. Teicher, B.A., Holden, S.A., Ara, G., Dupuis, N.P., Liu, F., Yuan, J., Ikebe, M., Kakeji, Y. Int. J. Cancer (1995) [Pubmed]
  13. Hypoxic cell turnover in different solid tumor lines. Ljungkvist, A.S., Bussink, J., Kaanders, J.H., Rijken, P.F., Begg, A.C., Raleigh, J.A., van der Kogel, A.J. Int. J. Radiat. Oncol. Biol. Phys. (2005) [Pubmed]
  14. Cerebral hemodynamic reserve and early neurologic deterioration in acute ischemic stroke. Alvarez, F.J., Segura, T., Castellanos, M., Leira, R., Blanco, M., Castillo, J., Dávalos, A., Serena, J. J. Cereb. Blood Flow Metab. (2004) [Pubmed]
  15. Effects of oxygen and carbon dioxide on human retinal circulation. Pakola, S.J., Grunwald, J.E. Invest. Ophthalmol. Vis. Sci. (1993) [Pubmed]
  16. Pharmacokinetics of varying doses of nicotinamide and tumour radiosensitisation with carbogen and nicotinamide: clinical considerations. Rojas, A., Hodgkiss, R.J., Stratford, M.R., Dennis, M.F., Johns, H. Br. J. Cancer (1993) [Pubmed]
  17. Carbogen-induced changes in rat mammary tumour oxygenation reported by near infrared spectroscopy. Hull, E.L., Conover, D.L., Foster, T.H. Br. J. Cancer (1999) [Pubmed]
  18. Effects of various oxygenation conditions on the enhancement by Fluosol-DA of melphalan antitumor activity. Teicher, B.A., Crawford, J.M., Holden, S.A., Cathcart, K.N. Cancer Res. (1987) [Pubmed]
  19. Abnormal panretinal response pattern to carbogen inhalation in experimental retinopathy of prematurity. Berkowitz, B.A., Penn, J.S. Invest. Ophthalmol. Vis. Sci. (1998) [Pubmed]
  20. Retinal thickness and subnormal retinal oxygenation response in experimental diabetic retinopathy. Luan, H., Roberts, R., Sniegowski, M., Goebel, D.J., Berkowitz, B.A. Invest. Ophthalmol. Vis. Sci. (2006) [Pubmed]
  21. Anterior chamber paracentesis and carbogen treatment of acute CRAO. Gombos, G.M. Ophthalmology (1996) [Pubmed]
  22. Potentiation of radiation-induced regrowth delay by isosorbide dinitrate in FSaII murine tumors. Jordan, B.F., Beghein, N., Aubry, M., Grégoire, V., Gallez, B. Int. J. Cancer (2003) [Pubmed]
  23. alpha-lipoic acid corrects late-phase supernormal retinal oxygenation response in experimental diabetic retinopathy. Roberts, R., Luan, H., Berkowitz, B.A. Invest. Ophthalmol. Vis. Sci. (2006) [Pubmed]
  24. Blocking ET-1 receptors does not correct subnormal retinal oxygenation response in experimental diabetic retinopathy. Roberts, R., Luan, H., Berkowitz, B.A. Invest. Ophthalmol. Vis. Sci. (2006) [Pubmed]
  25. Hypoxic radiosensitizers in radical radiotherapy for patients with bladder carcinoma: hyperbaric oxygen, misonidazole, and accelerated radiotherapy, carbogen and nicotinamide. Droller, M.J. J. Urol. (2000) [Pubmed]
  26. Specificity of subnormal deltaPO2 for retinal neovascularization in experimental retinopathy of prematurity. Zhang, W., Ito, Y., Berlin, E., Roberts, R., Luan, H., Berkowitz, B.A. Invest. Ophthalmol. Vis. Sci. (2003) [Pubmed]
  27. Effect of PKCbeta on retinal oxygenation response in experimental diabetes. Luan, H., Leitges, M., Gupta, R.R., Pacheco, D., Seidner, A., Liggett, J., Ito, Y., Kowluru, R., Berkowitz, B.A. Invest. Ophthalmol. Vis. Sci. (2004) [Pubmed]
  28. The optimal combination of hyperthermia and carbogen breathing to increase tumor oxygenation and radiation response. Griffin, R.J., Okajima, K., Song, C.W. Int. J. Radiat. Oncol. Biol. Phys. (1998) [Pubmed]
  29. The influence of carbogen breathing on tumour tissue oxygenation in man evaluated by computerised p02 histography. Falk, S.J., Ward, R., Bleehen, N.M. Br. J. Cancer (1992) [Pubmed]
  30. Hyperfractionated chemoradiation with carbogen breathing, with or without erythropoietin: a stepwise developed treatment schedule for advanced head-and-neck cancer. Martinez, J.C., Villar, A., Cabezon, M.A., de Serdio, J.L., Fuentes, C., Espiñeira, M., Perez, M.D., Gil, J., Artazkoz, J.J., Borque, C., Suñer, M., Saavedra, J.A. Int. J. Radiat. Oncol. Biol. Phys. (2001) [Pubmed]
  31. Mild temperature hyperthermia combined with carbogen breathing increases tumor partial pressure of oxygen (pO2) and radiosensitivity. Griffin, R.J., Okajima, K., Barrios, B., Song, C.W. Cancer Res. (1996) [Pubmed]
  32. Increase in pO2 and radiosensitivity of tumors by Fluosol-DA (20%) and carbogen. Song, C.W., Lee, I., Hasegawa, T., Rhee, J.G., Levitt, S.H. Cancer Res. (1987) [Pubmed]
  33. Changes in radiation sensitization induced by Fluosol-DA as measured by 31P nuclear magnetic resonance spectroscopy. Koutcher, J.A., Alfieri, A.A., Kornblith, A.B., Devitt, M.L., Cowburn, D., Ballon, D., Kim, J.H. Cancer Res. (1990) [Pubmed]
 
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