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Biomedical subjects

Richard L McGough

Publications and source records attributed to Richard L McGough.

5 recordsLinked to original sources

VEGF and BMP expression in mouse osteosarcoma cells.

Osteosarcoma is the most common primary bone malignancy. Despite improvements in therapy, approximately 30% of patients experience pulmonary metastasis. Expression of several growth factors, including VEGF and BMPs, has been implicated in tumor progression and metastatic potential. We hypothesized increased metastatic potential of mouse osteosarcoma cells positively correlates with the expression of VEGF and BMPs. We studied the expression patterns of these growth factors in two murine osteosarcoma cell lines with varying degrees of metastatic potential: K7M2 (highly metastatic) and K12 (minimally metastatic). Expression of VEGF and BMP2 were higher in the metastatic K7M2 cell line. We also investigated the effects of the BMP antagonist noggin on osteosarcoma growth characteristics in vitro. We noted decreased motility, altered morphology, and increased cell death in the highly metastatic K7M2 cell line. Less metastatic K12 cells showed substantial cell death without clear alteration of motility or morphology. These data suggest BMP2 expression may be an important factor in osteosarcoma metastasis and noggin administration theoretically could block its actions. Inhibition of BMPs and VEGF should be investigated further as a possible strategy for decreasing the incidence of pulmonary metastases in osteosarcoma.

Animals↗

Impact severity of local recurrence in giant cell tumor of bone.

UNLABELLED: We retrospectively reviewed 183 consecutive patients diagnosed with giant cell tumor at the three most common sites (distal femur, proximal tibia, and distal radius) to determine the pattern of local tumor recurrence and the impact severity of the recurrence on adjacent joint function. The primary tumor was treated in all patients with intralesional excision of tumor by curettage. Forty-five patients developed locally recurrent disease. Twenty-three of the patients had their first surgery at our institution, and 22 had been referred from other institutions after the development of local recurrence. The intrainstitutional recurrences were salvaged by a repeat curettage (n = 12) or en bloc osteoarticular resection (n = 10) for bone recurrences and wide local excision for soft tissue recurrence (n = 1). The prereferral recurrences were salvaged by a repeat curettage (n = 7) and en bloc osteoarticular resection (n = 15) for bone recurrences. Incomplete initial surgery, a delay in diagnosis of the recurrence of greater than 6 months, and subchondral recurrence of tumor were contributing factors in the failure to salvage the joint. Despite its benign histology, giant cell tumor of bone is an aggressive tumor that demands meticulous attention to surgical detail and close postoperative surveillance for successful local tumor control and durable, joint-preserving function. LEVEL OF EVIDENCE: Therapeutic study, Level III-2 (retrospective cohort study). See the Guidelines for Authors for a complete description of levels of evidence.

Adolescent↗

Angiogenic cytokines in cartilage tumors.

Pathologic neovascularization has been described in numerous types of cancers. The angiogenic cytokines vascular endothelial growth factor and basic fibroblast growth factor are thought to be the primary inducers of angiogenesis in these tumors. Hypoxia-inducible transcription factor is a nuclear transcription factor that promotes vascular endothelial growth factor expression. Prior studies have shown pathologic neovascularization in chondrosarcoma, which correlates with pathologic grade of the tumor. Angiogenic and nonangiogenic cartilage tumors were studied for expression of vascular endothelial growth factor, basic fibroblast growth factor and hypoxia-inducible transcription factors by immunohistochemistry and Northern blot analysis. Expression of vascular endothelial growth factor and hypoxia-inducible transcription factor were increased significantly in angiogenic tumors. Fibroblast growth factor expression was similar in angiogenic and nonangiogenic specimens. This may have implications for tumor grading and surgical decision-making, and potential treatment with antiangiogenesis chemotherapeutic agents.

Blotting, Northern↗

Pathologic neovascularization in cartilage tumors.

Tumor-induced angiogenesis is necessary to sustain radial growth of tumors. Increased microvascularity has been correlated with increased metastatic potential in breast, gastrointestinal, and gynecologic tumors, but has not been well studied in cartilaginous tumors. Grade II and Grade III chondrosarcomas have increased metastatic potential compared with Grade I tumors. One reason for this may be pathologic neovascularization. The purpose of the current study was to quantify the microvessel density of cartilage tumors. Seven Grade III, 17 Grade II, and eight Grade I chondrosarcomas, and 22 benign cartilage tumors were examined. Specimens were stained with antiCD34 antibody. Microvessel densities then were determined by direct counting and estimated using the Chalkley technique. Microvessel densities for Grade III and Grade II chondrosarcomas were 45.9 and 46.2 per high-power field and for Grade I and benign tumors the microvessel densities were 9.3 and 10.3. Microvessel densities of the aggressive tumors (Grades III and II) were greater than the microvessel densities of the nonaggressive tumors (Grade I and benign). Chalkley estimates confirmed the results. Microvascularity in cartilage tumors correlates with their biologic aggressiveness and seems promising as a variable to help with histopathologic grading and as a target for new treatment modalities.

Bone Neoplasms↗