Biomedical subjects

Jay S Wunder

Publications and source records attributed to Jay S Wunder.

40 records · Page 3Linked to original sources

PubMed2003

Cyclin alterations in giant cell tumor of bone.

Cyclins play an important role in regulating the passage of dividing cells through critical checkpoints in the cell cycle. Because alterations of several cyclins, especially cyclin D1, have been implicated in the development of many human neoplasms, we examined 32 cases of giant cell tumor of long bones for cyclin D1 gene amplification and protein overexpression using differential polymerase chain reaction and immunohistochemistry, respectively. In addition, the expression of cyclin D3, cyclin B1, and the proliferation-associated antigen Ki-67 (MIB-1) was assessed immunohistochemically. Low-level cyclin D1 gene amplification was detected in 61% of giant cell tumor cases. All tumors showed cyclin D1, cyclin D3, cyclin B1, and Ki-67 (MIB-1) staining; however, the distribution was very characteristic. Cyclin D1 protein expression was seen predominantly in the nuclei of the giant cells, with occasional mononuclear cells staining. There was no correlation between cyclin D1 gene amplification and protein overexpression. Cyclin D3 staining showed a similar distribution, with 88% of cases showing protein overexpression. Cyclin D1 and/or D3 staining in the giant cells was never associated with staining for either cyclin B1 or Ki-67 (MIB-1), as the expression of the latter two proteins was restricted to the mononuclear cells. Cyclin B1 overexpression was seen in 44% of cases. Ki-67 (MIB-1) staining was present in all cases, and between 10 to 50% of the mononuclear cells were positive. These results suggest that alterations in cyclin D1 and/or D3 might play a role in the pathogenesis of giant cell tumor of bone.

Adolescent↗

PubMed2003

Osseous invasion by soft-tissue sarcoma: assessment with MR imaging.

PURPOSE: To assess magnetic resonance (MR) imaging signs and overall accuracy of MR imaging for detection of osseous invasion by soft-tissue sarcoma, with histopathologic correlation as the reference standard. MATERIALS AND METHODS: Preoperative MR images (1.5 T, transverse and longitudinal planes, T1 and T2 weighted) of 56 osseous sites in 51 patients who underwent bone resection at surgery for soft-tissue sarcoma were assessed retrospectively for signs of osseous invasion, by consensus of two readers who were blinded to clinical and histopathologic findings. Delay between MR imaging and surgery averaged 34 days (range, 2-112 days). MR signs assessed included osseous abutment by tumor, maximal diameter of osseous abutment, extent of circumferential abutment of long bones (<25%, 25%-50%, >50%), cortical destruction, and cortical and medullary signal intensity change on T1- and T2-weighted images. Imaging findings were correlated with histopathologic findings. Sensitivities, specificities, positive and negative predictive values (PPV, NPV), and P values were calculated. RESULTS: Eleven sites (20%) showed osseous invasion histologically (two, cortical; nine, both cortical and medullary). Tumor abutted bone at 44 lesion sites (sensitivity, 100%; specificity, 27%). Maximal diameter of osseous abutment and extent of circumferential abutment did not significantly affect osseous invasion (P =.09 and.11, respectively). On T1- and T2-weighted images, 13 lesion sites showed cortical signal intensity change (sensitivity, 100%; specificity, 96%) and 10 showed cortical destruction (sensitivity, 82%; specificity, 98%). Eleven sites showed decreased medullary T1 signal intensity (sensitivity, 100%; specificity, 96%), and 12 showed increased medullary T2 signal intensity (sensitivity, 100%; specificity, 94%). MR imaging overall had a sensitivity of 100%, specificity of 93%, PPV of 79%, and NPV of 100% for detection of osseous invasion on the basis of any finding of cortical destruction or cortical or medullary signal intensity change on T1- or T2-weighted images (P <.001). CONCLUSION: On T1- and T2-weighted MR images, findings of cortical and medullary signal intensity change and cortical destruction were sensitive and specific for detection of osseous invasion by soft-tissue sarcoma.

Adolescent↗

PubMed2002

A mutant PTH/PTHrP type I receptor in enchondromatosis.

Enchondromas are common benign cartilage tumors of bone. They can occur as solitary lesions or as multiple lesions in enchondromatosis (Ollier and Maffucci diseases). Clinical problems caused by enchondromas include skeletal deformity and the potential for malignant change to chondrosarcoma. The extent of skeletal involvement is variable in enchondromatosis and may include dysplasia that is not directly attributable to enchondromas. Enchondromatosis is rare, obvious inheritance of the condition is unusual and no candidate loci have been identified. Enchondromas are usually in close proximity to, or in continuity with, growth-plate cartilage. Consequently, they may result from abnormal regulation of proliferation and terminal differentiation of chondrocytes in the adjoining growth plate. In normal growth plates, differentiation of proliferative chondrocytes to post-mitotic hypertrophic chondrocytes is regulated in part by a tightly coupled signaling relay involving parathyroid hormone related protein (PTHrP) and Indian hedgehog (IHH). PTHrP delays the hypertrophic differentiation of proliferating chondrocytes, whereas IHH promotes chondrocyte proliferation. We identified a mutant PTH/PTHrP type I receptor (PTHR1) in human enchondromatosis that signals abnormally in vitro and causes enchondroma-like lesions in transgenic mice. The mutant receptor constitutively activates Hedgehog signaling, and excessive Hedgehog signaling is sufficient to cause formation of enchondroma-like lesions.

Animals↗

PubMed2002

Giant cell tumor of long bone: a Canadian Sarcoma Group study.

A multicentric retrospective study of giant cell tumor of bone was conducted among Canadian surgeons. The hypothesis was that no differences would be found in health status, function, or recurrence rate irrespective to the nature of filling material or adjuvant used in patients treated with curettage. One hundred eighty-six cases were collected. There were 96 females and 90 males. The mean age of the patients was 36 years (range, 14-72 years), the minimum followup was 24 months, and the median followup was 60 months. Sixty-two percent of the tumors involved the knee region. One hundred fifty-eight were primary tumors and 28 were recurrences. Campanacci grading was as follows: Grade 1, seven patients; Grade 2, 100 patients; Grade 3, 76 patients; and unknown in three patients. Fifty-six patients had a pathologic fracture. Resection was done in 38 patients and 148 patients had curettage. The latter was supplemented with high speed burring in 135 patients, cement in 64 patients, various combinations of autograft or allograft bone in 61 patients, phenol in 37 patients, and liquid nitrogen in 10 patients. Structural allografts were used in 25 patients. The overall recurrence rate was 17%, 18% after curettage, and 16% after resection. Patients with primary tumors treated with curettage had a 10% recurrence rate. For recurrent lesions treated by curettage, the recurrence rate was 35%. The nature of the filling material used or the type of adjuvant method used or any combination of both failed to show any statistical impact on the recurrence risk. The results from the Musculoskeletal Tumor Society rating from 1987 were significantly lower in patients who sustained a displaced fracture. Results from the bodily pain section of the Short Form-36 also were found to be lower when a pathologic fracture was present. Results from the Musculoskeletal Tumor Society Rating 1987, the Short Form-36, and the Toronto Extremity Salvage Score did not show differences when either cement or bone graft were used after curettage.

Adolescent↗