Abstract
PURPOSE. The aim of this study was to quantify tumor cell proliferation and growth, analyze tumor blood vessel development, and determine the efficacy of antiangiogenic and angiostatic therapy in targeting mature vessels in retinal tumors of the LHBETATAG mouse model for retinoblastoma. METHODS. LHBETATAG mouse retinas were analyzed at 4, 8, 12, and 16 weeks of age. Tumor burden was analyzed by histology; cell proliferation, vessel density, angiogenesis, and vessel maturation were detected by immunofluorescence. To assess the efficacy of mature vessel targeting, 16-week-old mice were treated with single subconjunctival injections of the selective vascular-targeting drug combretastatin A4 prodrug (CA4P) or anecortave acetate, and eyes were analyzed 1 day and 1 week after injection to determine microvessel density and the number of angiogenic and mature vessels. RESULTS. Increased cell proliferation and angiogenesis were detected in the retinal inner nuclear layer (INL) before morphologic neoplastic changes were evident. As tumor size increased, angiogenesis diminished concomitantly with the appearance of mature vessels. Treatment with CA4P and anecortave acetate resulted in significant reductions in total vessel density. However, neither drug reduced the amount of α-smooth muscle actin (SMA)-positive, mature vessels. CONCLUSIONS. Results of this study provide new insight into the relationship between tumor growth and blood vessel development in the LHBETAT AG mouse and establish the framework for defining the selective action of two vessel-targeting drugs against new blood vessels compared with mature blood vessels. These findings suggest a high potential value in targeting the process of angiogenesis in the treatment of children with retinoblastoma.
| Original language | English |
|---|---|
| Pages (from-to) | 2476-2482 |
| Number of pages | 7 |
| Journal | Investigative Ophthalmology and Visual Science |
| Volume | 48 |
| Issue number | 6 |
| DOIs | |
| State | Published - Jun 1 2007 |
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ASJC Scopus subject areas
- Ophthalmology
Cite this
Retinoblastoma tumor vessel maturation impacts efficacy of vessel targeting in the LHBETATAG mouse model. / Jockovich, Maria Elena; Bajenaru, M. Livia; Piña, Yolanda; Suarez, Fernando; Feuer, William J; Fini, M. Elizabeth; Murray, Timothy G.
In: Investigative Ophthalmology and Visual Science, Vol. 48, No. 6, 01.06.2007, p. 2476-2482.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Retinoblastoma tumor vessel maturation impacts efficacy of vessel targeting in the LHBETATAG mouse model
AU - Jockovich, Maria Elena
AU - Bajenaru, M. Livia
AU - Piña, Yolanda
AU - Suarez, Fernando
AU - Feuer, William J
AU - Fini, M. Elizabeth
AU - Murray, Timothy G.
PY - 2007/6/1
Y1 - 2007/6/1
N2 - PURPOSE. The aim of this study was to quantify tumor cell proliferation and growth, analyze tumor blood vessel development, and determine the efficacy of antiangiogenic and angiostatic therapy in targeting mature vessels in retinal tumors of the LHBETATAG mouse model for retinoblastoma. METHODS. LHBETATAG mouse retinas were analyzed at 4, 8, 12, and 16 weeks of age. Tumor burden was analyzed by histology; cell proliferation, vessel density, angiogenesis, and vessel maturation were detected by immunofluorescence. To assess the efficacy of mature vessel targeting, 16-week-old mice were treated with single subconjunctival injections of the selective vascular-targeting drug combretastatin A4 prodrug (CA4P) or anecortave acetate, and eyes were analyzed 1 day and 1 week after injection to determine microvessel density and the number of angiogenic and mature vessels. RESULTS. Increased cell proliferation and angiogenesis were detected in the retinal inner nuclear layer (INL) before morphologic neoplastic changes were evident. As tumor size increased, angiogenesis diminished concomitantly with the appearance of mature vessels. Treatment with CA4P and anecortave acetate resulted in significant reductions in total vessel density. However, neither drug reduced the amount of α-smooth muscle actin (SMA)-positive, mature vessels. CONCLUSIONS. Results of this study provide new insight into the relationship between tumor growth and blood vessel development in the LHBETAT AG mouse and establish the framework for defining the selective action of two vessel-targeting drugs against new blood vessels compared with mature blood vessels. These findings suggest a high potential value in targeting the process of angiogenesis in the treatment of children with retinoblastoma.
AB - PURPOSE. The aim of this study was to quantify tumor cell proliferation and growth, analyze tumor blood vessel development, and determine the efficacy of antiangiogenic and angiostatic therapy in targeting mature vessels in retinal tumors of the LHBETATAG mouse model for retinoblastoma. METHODS. LHBETATAG mouse retinas were analyzed at 4, 8, 12, and 16 weeks of age. Tumor burden was analyzed by histology; cell proliferation, vessel density, angiogenesis, and vessel maturation were detected by immunofluorescence. To assess the efficacy of mature vessel targeting, 16-week-old mice were treated with single subconjunctival injections of the selective vascular-targeting drug combretastatin A4 prodrug (CA4P) or anecortave acetate, and eyes were analyzed 1 day and 1 week after injection to determine microvessel density and the number of angiogenic and mature vessels. RESULTS. Increased cell proliferation and angiogenesis were detected in the retinal inner nuclear layer (INL) before morphologic neoplastic changes were evident. As tumor size increased, angiogenesis diminished concomitantly with the appearance of mature vessels. Treatment with CA4P and anecortave acetate resulted in significant reductions in total vessel density. However, neither drug reduced the amount of α-smooth muscle actin (SMA)-positive, mature vessels. CONCLUSIONS. Results of this study provide new insight into the relationship between tumor growth and blood vessel development in the LHBETAT AG mouse and establish the framework for defining the selective action of two vessel-targeting drugs against new blood vessels compared with mature blood vessels. These findings suggest a high potential value in targeting the process of angiogenesis in the treatment of children with retinoblastoma.
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U2 - 10.1167/iovs.06-1397
DO - 10.1167/iovs.06-1397
M3 - Article
C2 - 17525173
AN - SCOPUS:34347259576
VL - 48
SP - 2476
EP - 2482
JO - Investigative Ophthalmology and Visual Science
JF - Investigative Ophthalmology and Visual Science
SN - 0146-0404
IS - 6
ER -