PubMed Health⌕ Search

Biomedical subjects

Gerald M Y Quan

Publications and source records attributed to Gerald M Y Quan.

6 recordsLinked to original sources

Anti-angiogenic therapy for osteosarcoma.

Even in tumor centers using established protocols, the survival rate of patients with osteosarcoma has not improved significantly in recent years. Novel therapies are urgently needed as an adjunct to conventional treatment modalities, to reduce the dose and subsequent toxicity associated with current chemotherapy, improve local disease control, prevent development of metastases, and offer an alternative treatment for those tumors that are poorly responsive to chemotherapy. Anti-angiogenic therapy currently holds great potential in conjunction with conventional treatment modalities for osteosarcoma. Specifically, anti-angiogenic factors derived from cartilage, a natural barrier to osteosarcoma invasion, may have important therapeutic applications in osteosarcoma.

Angiogenesis Inhibitors↗

Osteosarcoma near joints: assessment and implications.

BACKGROUND: The choice of performing surgery when tumors encroach onto joints remains a challenging and controversial issue. Pre-operative assessment by magnetic resonance imaging (MRI) is of critical importance in dictating surgical management and subsequent functional outcome. METHODS: We examined archival samples from 27 patients with osteosarcoma, adjacent to synovial joints for the incidence and mechanism of osteosarcoma extension into the joint space. Histopathologic findings were correlated with pre-operative MRI findings and choice of operation. RESULTS: There was no evidence of penetration across the entire thickness of articular cartilage into the joint cavity in all of the 27 cases. When pre-operative MRI confidently excluded joint involvement by tumor, enabling an intra-articular surgical approach, histopathologic correlation confirmed the absence of joint involvement in all cases. The low incidence of joint involvement was despite the presence of extensive bone and soft tissue involvement in most cases, a tendency for peripheral extension of tumor around the articular margin of the bone, and evidence of joint effusions pre-operatively in more than one-third of cases. CONCLUSIONS: Joint involvement by osteosarcoma is uncommon, with articular cartilage being a relative barrier to tumor invasion. If pre-operative MRI does not show definite evidence of intra-articular tumor involvement, it is likely to be safe to proceed with intra-articular resection.

Adolescent↗

Localization of pigment epithelium-derived factor in growing mouse bone.

Pigment epithelium-derived factor (PEDF) is a potent anti-angiogenic factor found in a wide range of fetal and adult tissues, where it is thought to play a role in the regulation of angiogenesis during development. The temporal expression of PEDF during endochondral bone formation has not previously been reported. In this study, we analysed the expression pattern of PEDF in growing mouse hindlimbs from newborn day one through to maturation at week 9, using immunohistochemistry and in situ hybridization. PEDF expression was demonstrated in chondrocytes within the resting, proliferative and upper hypertrophic zones of the epiphyseal growth plate. The pattern of expression was consistent throughout the developmental stages of the mouse. In addition, PEDF was expressed by osteoblasts lining the bone spicules in the ossification zone of metaphyseal bone, as well as by osteoblasts lining cortical periosteum. These novel results demonstrate that PEDF is developmentally expressed in both cartilage and bone cells during endochondral bone formation, and strongly suggest that it may play a regulatory role in the processes of chondrocyte and osteoblast differentiation, endochondral ossification, and bone remodelling during growth and development of long bones.

Animals↗

Resistance of epiphyseal cartilage to invasion by osteosarcoma is likely to be due to expression of antiangiogenic factors.

OBJECTIVES: Epiphyseal cartilage is a barrier to osteosarcoma invasion, however the mechanisms behind this resistance remain unclear. The aim of this study was to examine the chronological and spatial patterns of osteosarcoma growth and invasion of local tissue structures including epiphyseal cartilage. METHODS: We used an in vivomouse model of osteosarcoma to histologically examine tumors at different stages of disease progression. We compared the pattern of osteosarcoma penetration of epiphyseal cartilage with the expression pattern of two potent mediators of angiogenesis; proangiogenic vascular endothelial growth factor (VEGF) and antiangiogenic pigment epithelium-derived factor (PEDF). RESULTS: Epiphyseal cartilage remained intact across its entire length in all sections examined, despite increasing tumor size as well as intra- and extraosseous destruction. In the most advanced cases, only the proangiogenic lowermost layers of the hypertrophic zone of the growth plate were eroded. This corresponded with the growth plate layers which highly expressed the angiogenic factor VEGF. In contrast, the resting, proliferative and upper hypertrophic layers were resistant to osteosarcoma invasion in all cases. This corresponded to the layers with the highest expression of the potent antiangiogenic factor PEDF. CONCLUSION: Epiphyseal cartilage is resistant to local invasion by osteosarcoma. The balance of angiogenesis, influenced by pro- and antiangiogenic factors, is likely to play an important role in this resistance.

Animals↗