Abstract
The potential of the thymidylate synthase inhibitor, Tomudex to interact with ionizing radiation was assessed in vitro and in vivo in comparison with 5-fluorouracil. A concentration of 1 μM Tomudex decreased the shoulder of the radiation survival curves for normally oxygenated and hypoxic human HT- 29 colon carcinoma cells and human SCC-25 head and neck squamous carcinoma cells, resulting in enhancement ratios of 10 and 2.8 for normally oxygenated and hypoxic HT-29 cells at 5 Gray, respectively, and enhancement ratios of 19.5 and 2.7 for normally oxygenated and hypoxic SCC-25 cell at 5 Gray, respectively. Two schedules of Tomudex administered to animals bearing the Lewis lung carcinoma resulted in additive tumor growth delay with the fractionated radiation therapy. In nude mice bearing the HT-29 colon carcinoma grown as a xenograft, administration of Tomudex daily for 5 days on a 1 or 2-week schedule resulted in increased tumor growth delay along with fractionated radiation therapy on the same schedules. However, administration of Tomudex intermittently on a 2-week schedule appeared to be more interactive with daily fractionated radiation therapy on the 2-week schedule. In each assay, the results obtained with Tomudex were equal to or exceeded those obtained with 5-fluorouracil. These findings indicate that clinical trial of Tomudex along with fractionated radiation therapy is warranted.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 437-442 |
| Number of pages | 6 |
| Journal | International Journal of Oncology |
| Volume | 13 |
| Issue number | 3 |
| State | Published - Sep 1998 |
| Externally published | Yes |
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Keywords
- Colon carcinoma cells
- Head and neck squamous carcinoma cells
- Thymidylate synthase inhibitor
- Tomudex
ASJC Scopus subject areas
- Cancer Research
- Oncology
Cite this
Interaction of Tomudex with radiation in vitro and in vivo. / Teicher, Beverly A.; Ara, Gulshan; Chen, Ying Nan; Recht, Abram; Coleman, C. Norman.
In: International Journal of Oncology, Vol. 13, No. 3, 09.1998, p. 437-442.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Interaction of Tomudex with radiation in vitro and in vivo
AU - Teicher, Beverly A.
AU - Ara, Gulshan
AU - Chen, Ying Nan
AU - Recht, Abram
AU - Coleman, C. Norman
PY - 1998/9
Y1 - 1998/9
N2 - The potential of the thymidylate synthase inhibitor, Tomudex to interact with ionizing radiation was assessed in vitro and in vivo in comparison with 5-fluorouracil. A concentration of 1 μM Tomudex decreased the shoulder of the radiation survival curves for normally oxygenated and hypoxic human HT- 29 colon carcinoma cells and human SCC-25 head and neck squamous carcinoma cells, resulting in enhancement ratios of 10 and 2.8 for normally oxygenated and hypoxic HT-29 cells at 5 Gray, respectively, and enhancement ratios of 19.5 and 2.7 for normally oxygenated and hypoxic SCC-25 cell at 5 Gray, respectively. Two schedules of Tomudex administered to animals bearing the Lewis lung carcinoma resulted in additive tumor growth delay with the fractionated radiation therapy. In nude mice bearing the HT-29 colon carcinoma grown as a xenograft, administration of Tomudex daily for 5 days on a 1 or 2-week schedule resulted in increased tumor growth delay along with fractionated radiation therapy on the same schedules. However, administration of Tomudex intermittently on a 2-week schedule appeared to be more interactive with daily fractionated radiation therapy on the 2-week schedule. In each assay, the results obtained with Tomudex were equal to or exceeded those obtained with 5-fluorouracil. These findings indicate that clinical trial of Tomudex along with fractionated radiation therapy is warranted.
AB - The potential of the thymidylate synthase inhibitor, Tomudex to interact with ionizing radiation was assessed in vitro and in vivo in comparison with 5-fluorouracil. A concentration of 1 μM Tomudex decreased the shoulder of the radiation survival curves for normally oxygenated and hypoxic human HT- 29 colon carcinoma cells and human SCC-25 head and neck squamous carcinoma cells, resulting in enhancement ratios of 10 and 2.8 for normally oxygenated and hypoxic HT-29 cells at 5 Gray, respectively, and enhancement ratios of 19.5 and 2.7 for normally oxygenated and hypoxic SCC-25 cell at 5 Gray, respectively. Two schedules of Tomudex administered to animals bearing the Lewis lung carcinoma resulted in additive tumor growth delay with the fractionated radiation therapy. In nude mice bearing the HT-29 colon carcinoma grown as a xenograft, administration of Tomudex daily for 5 days on a 1 or 2-week schedule resulted in increased tumor growth delay along with fractionated radiation therapy on the same schedules. However, administration of Tomudex intermittently on a 2-week schedule appeared to be more interactive with daily fractionated radiation therapy on the 2-week schedule. In each assay, the results obtained with Tomudex were equal to or exceeded those obtained with 5-fluorouracil. These findings indicate that clinical trial of Tomudex along with fractionated radiation therapy is warranted.
KW - Colon carcinoma cells
KW - Head and neck squamous carcinoma cells
KW - Thymidylate synthase inhibitor
KW - Tomudex
UR - http://www.scopus.com/inward/record.url?scp=0031858463&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0031858463&partnerID=8YFLogxK
M3 - Article
C2 - 9683775
AN - SCOPUS:0031858463
VL - 13
SP - 437
EP - 442
JO - International Journal of Oncology
JF - International Journal of Oncology
SN - 1019-6439
IS - 3
ER -