Abstract
PURPOSE. To evaluate the mechanism and timing of retinal tumor cell death in the LHBETATAG mouse model of retinoblastoma after treatment with vascular targeting therapies and conventional therapies (focal chemotherapy and radiation). METHODS. For vascular targeting therapy, 12- or 16-week-old mice were treated with a single subconjunctival injection of either anecortave acetate (300 μg) or combretastatin A4 (1.5 mg). Eyes were analyzed at 1 day and 1 week after treatment. Tumor cell death was evaluated using TUNEL assays or immunofluorescence analysis of activated caspase 3 to detect apoptosis. Histopathologic analysis was performed to identify areas of necrosis. For conventional therapy, LHBETATAG mice were treated with six serial subconjunctival injections of focally delivered carboplatin chemotherapy (100 μg/delivery) or hyperfractionated external beam radiotherapy (EBRT; 15 Gy total dose). Cell death was analyzed by TUNEL assay. RESULTS. The highest levels of apoptotic cell death were seen 1 day after treatment in all treatment groups compared with vehicle controls. At 1 week after treatment, apoptotic cell death remained significantly elevated in the EBRT and carboplatin groups, but not after vessel targeting therapy. No significant necrosis was detected by histology in tumors of treated or of control eyes. CONCLUSIONS. Conventional therapies (focal carboplatin chemotherapy and EBRT) and vascular targeting agents significantly increase cell death through apoptosis, while not having a significant effect on necrosis in this murine model of retinoblastoma. These studies will aid in the optimization of delivery schemes of combined treatment modalities.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 5371-5376 |
| Number of pages | 6 |
| Journal | Investigative Ophthalmology and Visual Science |
| Volume | 48 |
| Issue number | 12 |
| DOIs | |
| State | Published - Dec 2007 |
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ASJC Scopus subject areas
- Ophthalmology
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Mechanism of retinoblastoma tumor cell death after focal chemotherapy, radiation, and vascular targeting therapy in a mouse model. / Jockovich, Maria Elena; Suarez, Fernando; Alegret, Armando; Piña, Yolanda; Hayden, Brandy; Cebulla, Colleen; Feuer, William J; Murray, Timothy G.
In: Investigative Ophthalmology and Visual Science, Vol. 48, No. 12, 12.2007, p. 5371-5376.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Mechanism of retinoblastoma tumor cell death after focal chemotherapy, radiation, and vascular targeting therapy in a mouse model
AU - Jockovich, Maria Elena
AU - Suarez, Fernando
AU - Alegret, Armando
AU - Piña, Yolanda
AU - Hayden, Brandy
AU - Cebulla, Colleen
AU - Feuer, William J
AU - Murray, Timothy G.
PY - 2007/12
Y1 - 2007/12
N2 - PURPOSE. To evaluate the mechanism and timing of retinal tumor cell death in the LHBETATAG mouse model of retinoblastoma after treatment with vascular targeting therapies and conventional therapies (focal chemotherapy and radiation). METHODS. For vascular targeting therapy, 12- or 16-week-old mice were treated with a single subconjunctival injection of either anecortave acetate (300 μg) or combretastatin A4 (1.5 mg). Eyes were analyzed at 1 day and 1 week after treatment. Tumor cell death was evaluated using TUNEL assays or immunofluorescence analysis of activated caspase 3 to detect apoptosis. Histopathologic analysis was performed to identify areas of necrosis. For conventional therapy, LHBETATAG mice were treated with six serial subconjunctival injections of focally delivered carboplatin chemotherapy (100 μg/delivery) or hyperfractionated external beam radiotherapy (EBRT; 15 Gy total dose). Cell death was analyzed by TUNEL assay. RESULTS. The highest levels of apoptotic cell death were seen 1 day after treatment in all treatment groups compared with vehicle controls. At 1 week after treatment, apoptotic cell death remained significantly elevated in the EBRT and carboplatin groups, but not after vessel targeting therapy. No significant necrosis was detected by histology in tumors of treated or of control eyes. CONCLUSIONS. Conventional therapies (focal carboplatin chemotherapy and EBRT) and vascular targeting agents significantly increase cell death through apoptosis, while not having a significant effect on necrosis in this murine model of retinoblastoma. These studies will aid in the optimization of delivery schemes of combined treatment modalities.
AB - PURPOSE. To evaluate the mechanism and timing of retinal tumor cell death in the LHBETATAG mouse model of retinoblastoma after treatment with vascular targeting therapies and conventional therapies (focal chemotherapy and radiation). METHODS. For vascular targeting therapy, 12- or 16-week-old mice were treated with a single subconjunctival injection of either anecortave acetate (300 μg) or combretastatin A4 (1.5 mg). Eyes were analyzed at 1 day and 1 week after treatment. Tumor cell death was evaluated using TUNEL assays or immunofluorescence analysis of activated caspase 3 to detect apoptosis. Histopathologic analysis was performed to identify areas of necrosis. For conventional therapy, LHBETATAG mice were treated with six serial subconjunctival injections of focally delivered carboplatin chemotherapy (100 μg/delivery) or hyperfractionated external beam radiotherapy (EBRT; 15 Gy total dose). Cell death was analyzed by TUNEL assay. RESULTS. The highest levels of apoptotic cell death were seen 1 day after treatment in all treatment groups compared with vehicle controls. At 1 week after treatment, apoptotic cell death remained significantly elevated in the EBRT and carboplatin groups, but not after vessel targeting therapy. No significant necrosis was detected by histology in tumors of treated or of control eyes. CONCLUSIONS. Conventional therapies (focal carboplatin chemotherapy and EBRT) and vascular targeting agents significantly increase cell death through apoptosis, while not having a significant effect on necrosis in this murine model of retinoblastoma. These studies will aid in the optimization of delivery schemes of combined treatment modalities.
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UR - http://www.scopus.com/inward/citedby.url?scp=38549144763&partnerID=8YFLogxK
U2 - 10.1167/iovs.07-0708
DO - 10.1167/iovs.07-0708
M3 - Article
C2 - 18055783
AN - SCOPUS:38549144763
VL - 48
SP - 5371
EP - 5376
JO - Investigative Ophthalmology and Visual Science
JF - Investigative Ophthalmology and Visual Science
SN - 0146-0404
IS - 12
ER -