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Efficacy of continuously administered PEDF-derived synthetic peptides against osteosarcoma growth and metastasis.

Broadhead ML, Choong PF, Dass CR - J. Biomed. Biotechnol. (2012)

Bottom Line: Neurotrophic, antiangiogenic, antiproliferative, and antimetastatic properties of PEDF have been attributed to a number of functional epitopes on the PEDF glycoprotein.StVOrth-2 (residues 78-102) and StVOrth-3 (residues 90-114) are two PEDF-derived peptides based on these functional epitopes.While treatment with StVOrth-2 and StVOrth-3 did not appear to affect local tumour invasion, tumour necrosis or apoptosis, StVOrth-2 predominantly restricted the growth of primary tumours, while StVOrth-3 restricted the burden of pulmonary metastatic disease.

View Article: PubMed Central - PubMed

Affiliation: Department of Orthopaedics and Department of Surgery, St. Vincent's Hospital, University of Melbourne, Fitzroy VIC 3065, Australia. matthew.broadhead@gmail.com

ABSTRACT
The potent antiangiogenic pigment epithelium-derived factor (PEDF) has shown promise against osteosarcoma, a tumour that originates in the bone and metastasises to the lungs. Neurotrophic, antiangiogenic, antiproliferative, and antimetastatic properties of PEDF have been attributed to a number of functional epitopes on the PEDF glycoprotein. StVOrth-2 (residues 78-102) and StVOrth-3 (residues 90-114) are two PEDF-derived peptides based on these functional epitopes. StVOrth-2 has previously been shown to inhibit osteosarcoma cell proliferation, while StVOrth-3 increased osteosarcoma cell adhesion to collagen I in vitro. In this paper, we have evaluated systemically and continuously delivered StVOrth-2 and StVOrth-3 using a clinically relevant murine model of osteosarcoma with spontaneous metastasis. Treatment with StVOrth-2 or StVOrth-3 with microosmotic pumps was initiated after primary osteosarcoma was established in the tibia. While treatment with StVOrth-2 and StVOrth-3 did not appear to affect local tumour invasion, tumour necrosis or apoptosis, StVOrth-2 predominantly restricted the growth of primary tumours, while StVOrth-3 restricted the burden of pulmonary metastatic disease. No peptide caused gross toxicity in mouse tissues as assessed by measuring weight of animals, serum biochemistry, and gross tissue observation. The differential effects exhibited by StVOrth-2 and StVOrth-3 in this orthotopic model of osteosarcoma may be related to the functional epitopes on the PEDF glycoprotein that they represent.

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Related in: MedlinePlus

(a) Animal weights recorded at days 20, 23, 27, 30, and 34 after SaOS-2 intratibial injection. There was no significant weight loss compared to control. (b) Biochemical analysis of serum collected postmortem (±SEM). There was no evidence of renal or hepatic toxicity.
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fig2: (a) Animal weights recorded at days 20, 23, 27, 30, and 34 after SaOS-2 intratibial injection. There was no significant weight loss compared to control. (b) Biochemical analysis of serum collected postmortem (±SEM). There was no evidence of renal or hepatic toxicity.

Mentions: Mice were studied for potential systemic side affects associated with delivery of StVOrth-2 (residues 78–102) and StVOrth-3 (residues 90–114) (see Figure 1). Mice were regularly monitored during the study for signs of distress and animal weights were recorded twice weekly. All mice remained well for the duration of the study, and no significant weight loss compared to control was observed (two-way ANOVA) (Figure 2(a)).


Efficacy of continuously administered PEDF-derived synthetic peptides against osteosarcoma growth and metastasis.

Broadhead ML, Choong PF, Dass CR - J. Biomed. Biotechnol. (2012)

(a) Animal weights recorded at days 20, 23, 27, 30, and 34 after SaOS-2 intratibial injection. There was no significant weight loss compared to control. (b) Biochemical analysis of serum collected postmortem (±SEM). There was no evidence of renal or hepatic toxicity.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3369529&req=5

fig2: (a) Animal weights recorded at days 20, 23, 27, 30, and 34 after SaOS-2 intratibial injection. There was no significant weight loss compared to control. (b) Biochemical analysis of serum collected postmortem (±SEM). There was no evidence of renal or hepatic toxicity.
Mentions: Mice were studied for potential systemic side affects associated with delivery of StVOrth-2 (residues 78–102) and StVOrth-3 (residues 90–114) (see Figure 1). Mice were regularly monitored during the study for signs of distress and animal weights were recorded twice weekly. All mice remained well for the duration of the study, and no significant weight loss compared to control was observed (two-way ANOVA) (Figure 2(a)).

Bottom Line: Neurotrophic, antiangiogenic, antiproliferative, and antimetastatic properties of PEDF have been attributed to a number of functional epitopes on the PEDF glycoprotein.StVOrth-2 (residues 78-102) and StVOrth-3 (residues 90-114) are two PEDF-derived peptides based on these functional epitopes.While treatment with StVOrth-2 and StVOrth-3 did not appear to affect local tumour invasion, tumour necrosis or apoptosis, StVOrth-2 predominantly restricted the growth of primary tumours, while StVOrth-3 restricted the burden of pulmonary metastatic disease.

View Article: PubMed Central - PubMed

Affiliation: Department of Orthopaedics and Department of Surgery, St. Vincent's Hospital, University of Melbourne, Fitzroy VIC 3065, Australia. matthew.broadhead@gmail.com

ABSTRACT
The potent antiangiogenic pigment epithelium-derived factor (PEDF) has shown promise against osteosarcoma, a tumour that originates in the bone and metastasises to the lungs. Neurotrophic, antiangiogenic, antiproliferative, and antimetastatic properties of PEDF have been attributed to a number of functional epitopes on the PEDF glycoprotein. StVOrth-2 (residues 78-102) and StVOrth-3 (residues 90-114) are two PEDF-derived peptides based on these functional epitopes. StVOrth-2 has previously been shown to inhibit osteosarcoma cell proliferation, while StVOrth-3 increased osteosarcoma cell adhesion to collagen I in vitro. In this paper, we have evaluated systemically and continuously delivered StVOrth-2 and StVOrth-3 using a clinically relevant murine model of osteosarcoma with spontaneous metastasis. Treatment with StVOrth-2 or StVOrth-3 with microosmotic pumps was initiated after primary osteosarcoma was established in the tibia. While treatment with StVOrth-2 and StVOrth-3 did not appear to affect local tumour invasion, tumour necrosis or apoptosis, StVOrth-2 predominantly restricted the growth of primary tumours, while StVOrth-3 restricted the burden of pulmonary metastatic disease. No peptide caused gross toxicity in mouse tissues as assessed by measuring weight of animals, serum biochemistry, and gross tissue observation. The differential effects exhibited by StVOrth-2 and StVOrth-3 in this orthotopic model of osteosarcoma may be related to the functional epitopes on the PEDF glycoprotein that they represent.

Show MeSH
Related in: MedlinePlus