Enhancement of Tumor Response to  -Radiation by an Inhibitor of Cyclooxygenase-2 Enzyme

Milas, Luka; Kishi, Kazushi; Hunter, Nancy; Mason, Kathryn A.; Masferrer, Jaime L.; Tofilon, Philip J.

doi:10.1093/jnci/91.17.1501

Cited by 209 publications

(110 citation statements)

References 13 publications

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“…When mean TD was 8.4+0.4 mm, at which time micrometastases are already present in the lungs, treatment with 6 mg kg 71 SC-236 (15.6 mM) or 3 mg kg 71 indomethacin (8.3 mM) was initiated. These doses were based on pilot studies and previously published doses (Milas et al, 1999). Although 3 mg kg 71 indomethacin has previously been found to be toxic when administered by gavage , we did not observe any toxicity using intra-peritoneal delivery.…”

Section: Effect Of Cox Inhibition On Primary Tumour Growth and Metastmentioning

confidence: 92%

“…When mean TD was 8.4+0.4 mm (day 12 post injection of tumour cells), at which time micrometastases are already present in the lungs, mice were randomised into one of three groups (n=6 per group) to receive daily intraperitoneal injections of 200 ml vehicle (1% v v 71 dimethylsulphoxide [DMSO]), the selective COX-2 inhibitor, SC-236 (kind gift from Dr P Isakson, Monsanto, St Louis, MI, USA), (6 mg kg 71 in 1% DMSO) or the non-selective COX inhibitor, indomethacin (3 mg kg 71 in 1% DMSO). These doses were selected based on previously published studies (Milas et al, 1999), pilot studies and known toxicity of indomethacin. Tumour diameters were measured on alternate days.…”

Section: Experimental Designmentioning

confidence: 99%

“…The anti-angiogenic and pro-apoptotic properties of COX inhibitors, suggest that these drugs may increase the anti-tumour effects of conventional chemotherapy and radiotherapy used in the treatment of breast cancer. Indeed, SC-236 has been shown to increase radiosensitivity in a murine sarcoma model (Milas et al, 1999). …”

Section: Experimental Therapeuticsmentioning

confidence: 99%

“…Non-steroidal anti-inflammatory drugs (NSAIDs) inhibit cyclooxygenase enzymes and consequently can inhibit, or abolish the effects of prostaglandins (Bjorkman, 1998;Hawkey, 1999). Increasing evidence shows that NSAIDs can inhibit tumour growth in experimental animals and in humans (Taketo, 1998;Milas, 1999). Commonly used NSAIDS, such as indomethacin, inhibit both COX-1 and COX-2 but treatment with such agents may be limited by toxicity to normal tissues, particularly ulceration and bleeding in the gastrointestinal tract as a consequence of COX-1 inhibition (Milas et al, 1999 and refs therein).…”

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confidence: 99%

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Cyclo-oxygenase inhibition reduces tumour growth and metastasis in an orthotopic model of breast cancer

et al. 2002

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The effect of selective and non-selective cyclo-oxygenase inhibition on tumour growth and metastasis in an orthotopic model of breast cancer was investigated. 4T1 mammary adenocarcinoma cells were injected into the mammary fat pad of female BALB/c mice. When tumours reached a mean tumour diameter of 8.4+0.4 mm, mice were randomised into three groups (n=6 per group) and received daily intraperitoneal injections of the selective cyclo-oxygenase-2 inhibitor, SC-236, the non selective cyclo-oxygenase inhibitor, Indomethacin, or drug vehicle. Tumour diameter was recorded on alternate days. From 8 days after initiation of treatment, tumour diameter in animals treated with either SC-236 or indomethacin was significantly reduced relative to controls. Both primary tumour weight and the number of lung metastases were significantly reduced in the SC-236 and indomethacin treated mice. Microvessel density was reduced and tumor cell apoptosis increased in the primary tumour of mice treated with either the selective or non-selective cyclo-oxygenase inhibitor. In vitro, cyclo-oxygenase inhibition decreased vascular endothelial growth factor production and increased apoptosis of tumour cells. Our results suggest that cyclo-oxygenase inhibitors will be of value in the treatment of both primary and metastatic breast cancer.

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Section: Effect Of Cox Inhibition On Primary Tumour Growth and Metastmentioning

confidence: 92%

Section: Experimental Designmentioning

confidence: 99%

Section: Experimental Therapeuticsmentioning

confidence: 99%

mentioning

confidence: 99%

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Cyclo-oxygenase inhibition reduces tumour growth and metastasis in an orthotopic model of breast cancer

et al. 2002

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“…More recently, COX-2 has been also associated with oncogenic transformation and angiogenesis (15,20), and studies using COX inhibitors support this notion (45). A COX-2 inhibitor has also been reported to increase the radiosensitivity of mice bearing a new fibrosarcoma (46). Strong evidence for a role of COX-2 and PGs in skin tumor promotion comes from initiation-promotion studies using COX-2 deficient mice, which showed a significant reduction in skin cancer development (47,48).…”

Section: Discussionmentioning

confidence: 99%