Modulation of tumor oxygenation and radio sensitivity by a perfluorooctylbromide emulsion

Rockwell, Sara; Kelley, Marianne; Irvin, Carolyn G.; Hughes, Claire; Porter, Elizabeth; Yabuki, Hiroko; Fischer, James J.

doi:10.1016/0167-8140(91)90003-y

Cited by 37 publications

(16 citation statements)

References 33 publications

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“…Some studies were performed with one tumour cell line and various methods to increase or decrease radiosensitivity , Rockwell et al 1991, Lee and Song 1992 . Other studies compare p0 2 and the radiobiological fraction of hypoxic cells in different lines (Vaupel et al .…”

Section: Discussionmentioning

confidence: 99%

“…Similar results were obtained when 0 2 tension (Lee et al . 1990) was measured in rodent tumours using microelectrodes , Rockwell et al . 1991 .…”

Section: Discussionmentioning

confidence: 99%

“…1989) . The first set of studies used different anaesthetics , Lee and Song 1992 and different experimental protocols (Rockwell 1991) for P02 measurements and radiosensitivity studies . Rectal temperature was controlled only for p0 2 measurements and only in the study of Lee and Song (1992) .…”

Section: Discussionmentioning

confidence: 99%

“…While it has been shown that an increase in P0 2 is accompanied by increased radiosensitivity in rodent tumours , Lee et al . 1990, 1992, Rockwell et al . 1991, Vitu et al .…”

Section: Introductionmentioning

confidence: 95%

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Nicotinamide and Carbogen: Relationship betweenpO₂and Radiosensitivity in Three Tumour Lines

Martin

Thomas

Guichard

1994

International Journal of Radiation Biology

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The effects of carbogen breathing, nicotinamide injection and their combination on tumour radiosensitivity were correlated with changes in tumour O2 tension to determine the relationship between radiosensitivity and measured pO2. The radiosensitivity (in vivo-in vitro colony assay) and O2 tension (computerized pO2 histograph KIMOC 6650) of two human xenografted tumours (HRT18 and Na11+) and one murine tumour (EMT6) were measured under similar experimental conditions. A single dose of radiation was delivered (8 Gy for HRT18 and Na11+, 12 Gy for EMT6). Carbogen breathing, nicotinamide injection, and their combination all significantly increased radiosensitivity in the three cell lines (p < 0.05); the most efficient treatment was carbogen plus nicotinamide. The radiosensitization was optimum for EMT6 and Na11+. Mean and median pO2 increased with all three treatments, except for carbogen breathing in EMT6. Carbogen breathing had little effect on the proportion of low pO2 values, but induced pO2 values > 30 mmHg in all three tumour lines. Nicotinamide decreased the proportion of low pO2 values. This effect is larger with the combination carbogen plus nicotinamide. Almost all pO2 values < 2.5 mmHg were eliminated for HRT18 and EMT6. The relationship between radiosensitization and pO2 was significant when pO2 was expressed as the percentage of values below 7, 8, 9 and 10 mmHg for the three lines.

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Section: Discussionmentioning

confidence: 99%

“…Similar results were obtained when 0 2 tension (Lee et al . 1990) was measured in rodent tumours using microelectrodes , Rockwell et al . 1991 .…”

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

“…While it has been shown that an increase in P0 2 is accompanied by increased radiosensitivity in rodent tumours , Lee et al . 1990, 1992, Rockwell et al . 1991, Vitu et al .…”

Section: Introductionmentioning

confidence: 95%

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Nicotinamide and Carbogen: Relationship betweenpO₂and Radiosensitivity in Three Tumour Lines

Martin

Thomas

Guichard

1994

International Journal of Radiation Biology

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“…Measurements of extracellular pH using microelectrodes have shown regional variations in pH, with pH varying from 7.2 to 5.9 within the tumors (35). Other studies have shown that the oxygenation of the tumors can be improved by appropriate concomitant treatments with hyperbaric oxygen, carbogen, perflourochemical emulsions, allosteric effectors of hemoglobin, texaphyrins, or pentoxyfiline, and that these treatments provide the anticipated improvements in the response of the tumors to irradiation (2–4, 37–39). Past studies have also shown that hypoxic cell radiosensitizers such as misonidazole increase the radiosensitivity of the hypoxic tumor cells (3, 10, 27), and that drugs preferentially toxic to hypoxic cells, including mitomycin C, porfiromycin and KS119, as well as misonidazole, kill cells in the tumor cell populations that demonstrate hypoxic radioresistance (3, 9, 10, 21, 35, 40).…”

Section: Methodsmentioning

confidence: 99%

Preliminary Studies with a New Hypoxia-Selective Cytotoxin, KS119W,In VitroandIn Vivo

et al. 2012

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Agents with selective toxicity to hypoxic cells have shown promise as adjuncts to radiotherapy. Our previous studies showed that the bioreductive alkylating agent KS119 had an extremely large differential toxicity to severely hypoxic and aerobic cells in cell culture, and was effective in killing the hypoxic cells of EMT6 mouse mammary tumors in vivo. However, the limited solubility of that compound precluded its development as an anticancer drug. Here we report our initial studies with KS119W, a water-soluble analog of KS119. The cytotoxicity of KS119W to EMT6 cells in vitro was similar to that of KS119, with both agents producing only minimal cytotoxicity to aerobic cells even after intensive treatments, while producing pronounced cytotoxicity to oxygen-deficient cells. This resulted in large differentials in the toxicities to hypoxic and aerobic cells (.1,000-fold at 10 μM). Low pH had only minimal effects on the cytotoxicity of KS119W. Under hypoxic conditions, EMT6 cells transfected to express high levels of either human or mouse versions of the repair protein O6-alkylguanine-DNA alkyltransferase, which is also known as O6-methylguanine DNA-methyltransferase, were much more resistant to KS119W than parental EMT6 cells lacking O6-alkylguanine-DNA alkyltransferase, confirming the importance of DNA O-6-alkylation to the cytotoxicity of this agent. Studies with EMT6 tumors in BALB/c Rw mice using both tumor cell survival and tumor growth delay assays showed that KS119W was effective as an adjunct to irradiation for the treatment of solid tumors in vivo, producing additive or supra-additive effects in most combination regimens for which the interactions could be evaluated. Our findings encourage additional preclinical studies to examine further the antineoplastic effects of KS119W alone and in combination with radiation, and to examine the pharmacology and toxicology of this new bioreductive alkylating agent so that its potential for clinical use as an adjuvant to radiotherapy can be evaluated.

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Pentoxifylline improves the oxygenation and radiation response of BA1112 rat rhabdomyosarcomas and EMT6 mouse mammary carcinomas

Collingridge

Rockwell

2000

Int. J. Cancer

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Tumor hypoxia can significantly impact the efficacy of cancer therapy. Pentoxifylline, a methylxanthine derivative, can improve oxygen delivery to tissues and is widely used in the treatment of peripheral vascular disease and various cerebrovascular disorders. In this article, we show that pentoxifylline, combined with oxygen breathing, significantly improves the radiation response of two experimental tumors in vivo through improved tumor oxygenation. We also demonstrate that pentoxifylline does not directly radiosensitize EMT6 cells in vitro and does not modify the tumor radiation response when administered postirradiation to solid EMT6 tumors. Our findings confirm that preirradiation administration of pentoxifylline can improve radiation efficacy, but suggest that its role as a postirradiation modifier of treatment response, reported by others, may be tumor‐specific. Int. J. Cancer (Radiat. Oncol. Invest.) 90, 256–264 (2000). © 2000 Wiley‐Liss, Inc.

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Modulation of tumor oxygenation and radio sensitivity by a perfluorooctylbromide emulsion

Cited by 37 publications

References 33 publications

Nicotinamide and Carbogen: Relationship betweenpO₂and Radiosensitivity in Three Tumour Lines

Nicotinamide and Carbogen: Relationship betweenpO₂and Radiosensitivity in Three Tumour Lines

Preliminary Studies with a New Hypoxia-Selective Cytotoxin, KS119W,In VitroandIn Vivo

Pentoxifylline improves the oxygenation and radiation response of BA1112 rat rhabdomyosarcomas and EMT6 mouse mammary carcinomas

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Modulation of tumor oxygenation and radio sensitivity by a perfluorooctylbromide emulsion

Cited by 37 publications

References 33 publications

Nicotinamide and Carbogen: Relationship betweenpO2and Radiosensitivity in Three Tumour Lines

Nicotinamide and Carbogen: Relationship betweenpO2and Radiosensitivity in Three Tumour Lines

Preliminary Studies with a New Hypoxia-Selective Cytotoxin, KS119W,In VitroandIn Vivo

Pentoxifylline improves the oxygenation and radiation response of BA1112 rat rhabdomyosarcomas and EMT6 mouse mammary carcinomas

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Product

Resources

About

Nicotinamide and Carbogen: Relationship betweenpO₂and Radiosensitivity in Three Tumour Lines

Nicotinamide and Carbogen: Relationship betweenpO₂and Radiosensitivity in Three Tumour Lines