Anecortave acetate as single and adjuvant therapy in the treatment of retinal tumors of LHBETATAG mice

Maria Elena Jockovich, Timothy G. Murray, Erika Escalona-Benz, Eleut Hernandez, William J Feuer

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Abstract

PURPOSE. To evaluate the tumor control efficacy of the antiangiogenic agent anecortave acetate as single and combined therapy, in retinal tumor reduction using the LHBETATAG mouse model of retinoblastoma. METHODS. Group A: Ten-week-old, LHBETATAG mice received a single subconjunctival injection of anecortave acetate (1200, 600, 300, and 150 μg) delivered to right eyes only. Group B: Ten-week-old, LH BETATAG mice received a single subconjunctival injection of anecortave acetate (600, 300, and 150 μg) delivered to right eyes only, either during a cycle of carboplatin (six subconjunctival deliveries) or after the completed cycle. Carboplatin was delivered at the subtherapeutic concentration of 62.5 μg. All animals were euthanatized at 16 weeks of age, and the eyes were examined histopathologically. RESULTS. A statistically significant reduction in tumor burden was detected after a single periocular injection of anecortave acetate. The reduction of tumor burden followed a U-shaped dose-response curve. Tumor burden was significantly decreased when anecortave acetate and carboplatin were combined. However, varying doses and delivery schedule of these agents had significant impact on the effectiveness of the combined treatment. The most effective scheme was delivering a low dose (150-300 μg) of anecortave acetate after a complete cycle of carboplatin. Histopathological evaluation showed no signs of retinal toxicity to anecortave acetate delivery alone or in combination with carboplatin. CONCLUSIONS. Anecortave acetate, as monotherapy or as adjuvant therapy, significantly controlled tumor burden in a murine model of retinoblastoma. Moreover, adjuvant therapy enabled the use of typically subtherapeutic carboplatin doses without decreasing efficacy of the therapy.

Original languageEnglish (US)
Pages (from-to)1264-1268
Number of pages5
JournalInvestigative Ophthalmology and Visual Science
Volume47
Issue number4
DOIs
StatePublished - Apr 2006

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Retinal Neoplasms
Carboplatin
Tumor Burden
Retinoblastoma
Therapeutics
Intraocular Injections
Injections
Angiogenesis Inhibitors
anecortave acetate
Appointments and Schedules

ASJC Scopus subject areas

  • Ophthalmology

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Anecortave acetate as single and adjuvant therapy in the treatment of retinal tumors of LHBETATAG mice. / Jockovich, Maria Elena; Murray, Timothy G.; Escalona-Benz, Erika; Hernandez, Eleut; Feuer, William J.

In: Investigative Ophthalmology and Visual Science, Vol. 47, No. 4, 04.2006, p. 1264-1268.

Research output: Contribution to journalArticle

Jockovich, Maria Elena ; Murray, Timothy G. ; Escalona-Benz, Erika ; Hernandez, Eleut ; Feuer, William J. / Anecortave acetate as single and adjuvant therapy in the treatment of retinal tumors of LHBETATAG mice. In: Investigative Ophthalmology and Visual Science. 2006 ; Vol. 47, No. 4. pp. 1264-1268.
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abstract = "PURPOSE. To evaluate the tumor control efficacy of the antiangiogenic agent anecortave acetate as single and combined therapy, in retinal tumor reduction using the LHBETATAG mouse model of retinoblastoma. METHODS. Group A: Ten-week-old, LHBETATAG mice received a single subconjunctival injection of anecortave acetate (1200, 600, 300, and 150 μg) delivered to right eyes only. Group B: Ten-week-old, LH BETATAG mice received a single subconjunctival injection of anecortave acetate (600, 300, and 150 μg) delivered to right eyes only, either during a cycle of carboplatin (six subconjunctival deliveries) or after the completed cycle. Carboplatin was delivered at the subtherapeutic concentration of 62.5 μg. All animals were euthanatized at 16 weeks of age, and the eyes were examined histopathologically. RESULTS. A statistically significant reduction in tumor burden was detected after a single periocular injection of anecortave acetate. The reduction of tumor burden followed a U-shaped dose-response curve. Tumor burden was significantly decreased when anecortave acetate and carboplatin were combined. However, varying doses and delivery schedule of these agents had significant impact on the effectiveness of the combined treatment. The most effective scheme was delivering a low dose (150-300 μg) of anecortave acetate after a complete cycle of carboplatin. Histopathological evaluation showed no signs of retinal toxicity to anecortave acetate delivery alone or in combination with carboplatin. CONCLUSIONS. Anecortave acetate, as monotherapy or as adjuvant therapy, significantly controlled tumor burden in a murine model of retinoblastoma. Moreover, adjuvant therapy enabled the use of typically subtherapeutic carboplatin doses without decreasing efficacy of the therapy.",
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N2 - PURPOSE. To evaluate the tumor control efficacy of the antiangiogenic agent anecortave acetate as single and combined therapy, in retinal tumor reduction using the LHBETATAG mouse model of retinoblastoma. METHODS. Group A: Ten-week-old, LHBETATAG mice received a single subconjunctival injection of anecortave acetate (1200, 600, 300, and 150 μg) delivered to right eyes only. Group B: Ten-week-old, LH BETATAG mice received a single subconjunctival injection of anecortave acetate (600, 300, and 150 μg) delivered to right eyes only, either during a cycle of carboplatin (six subconjunctival deliveries) or after the completed cycle. Carboplatin was delivered at the subtherapeutic concentration of 62.5 μg. All animals were euthanatized at 16 weeks of age, and the eyes were examined histopathologically. RESULTS. A statistically significant reduction in tumor burden was detected after a single periocular injection of anecortave acetate. The reduction of tumor burden followed a U-shaped dose-response curve. Tumor burden was significantly decreased when anecortave acetate and carboplatin were combined. However, varying doses and delivery schedule of these agents had significant impact on the effectiveness of the combined treatment. The most effective scheme was delivering a low dose (150-300 μg) of anecortave acetate after a complete cycle of carboplatin. Histopathological evaluation showed no signs of retinal toxicity to anecortave acetate delivery alone or in combination with carboplatin. CONCLUSIONS. Anecortave acetate, as monotherapy or as adjuvant therapy, significantly controlled tumor burden in a murine model of retinoblastoma. Moreover, adjuvant therapy enabled the use of typically subtherapeutic carboplatin doses without decreasing efficacy of the therapy.

AB - PURPOSE. To evaluate the tumor control efficacy of the antiangiogenic agent anecortave acetate as single and combined therapy, in retinal tumor reduction using the LHBETATAG mouse model of retinoblastoma. METHODS. Group A: Ten-week-old, LHBETATAG mice received a single subconjunctival injection of anecortave acetate (1200, 600, 300, and 150 μg) delivered to right eyes only. Group B: Ten-week-old, LH BETATAG mice received a single subconjunctival injection of anecortave acetate (600, 300, and 150 μg) delivered to right eyes only, either during a cycle of carboplatin (six subconjunctival deliveries) or after the completed cycle. Carboplatin was delivered at the subtherapeutic concentration of 62.5 μg. All animals were euthanatized at 16 weeks of age, and the eyes were examined histopathologically. RESULTS. A statistically significant reduction in tumor burden was detected after a single periocular injection of anecortave acetate. The reduction of tumor burden followed a U-shaped dose-response curve. Tumor burden was significantly decreased when anecortave acetate and carboplatin were combined. However, varying doses and delivery schedule of these agents had significant impact on the effectiveness of the combined treatment. The most effective scheme was delivering a low dose (150-300 μg) of anecortave acetate after a complete cycle of carboplatin. Histopathological evaluation showed no signs of retinal toxicity to anecortave acetate delivery alone or in combination with carboplatin. CONCLUSIONS. Anecortave acetate, as monotherapy or as adjuvant therapy, significantly controlled tumor burden in a murine model of retinoblastoma. Moreover, adjuvant therapy enabled the use of typically subtherapeutic carboplatin doses without decreasing efficacy of the therapy.

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