Limitations of single slice dynamic contrast enhanced MR in pharmacokinetic modeling of bone sarcomas.

Background: Single slice dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) appears to provide perfusion data about sarcomas in vivo that correlate with tumor necrosis on equivalent pathological sections. However, sarcomas are heterogeneous and therefore single slice DCE-MRI may not correlate with total tumor necrosis.

Purpose: To determine whether changes in pharmacokinetic modeling of DCE-MRI, during chemotherapy for primary bone sarcomas correlated with histological measures of total tumor necrosis.

Bone fractures following external beam radiotherapy and limb-preservation surgery for lower extremity soft tissue sarcoma: relationship to irradiated bone length, volume, tumor location and dose.

Purpose: To examine the relationship between tumor location, bone dose, and irradiated bone length on the development of radiation-induced fractures for lower extremity soft tissue sarcoma (LE-STS) patients treated with limb-sparing surgery and radiotherapy (RT).

Methods And Materials: Of 691 LE-STS patients treated from 1989 to 2005, 31 patients developed radiation-induced fractures. Analysis was limited to 21 fracture patients (24 fractures) who were matched based on tumor size and location, age, beam arrangement, and mean total cumulative RT dose to a random sample of 53 nonfracture patients and compared for fracture risk factors.

Evolution of MIR168 paralogs in Brassicaceae.

Background: In plants, expression of ARGONAUTE1 (AGO1), the catalytic subunit of the RNA-Induced Silencing Complex responsible for post-transcriptional gene silencing, is controlled through a feedback loop involving the miR168 microRNA. This complex auto-regulatory loop, composed of miR168-guided AGO1-catalyzed cleavage of AGO1 mRNA and AGO1-mediated stabilization of miR168, was shown to ensure the maintenance of AGO1 homeostasis that is pivotal for the correct functioning of the miRNA pathway.

Results: We applied different approaches to studying the genomic organization and the structural and functional evolution of MIR168 homologs in Brassicaeae.

Management of vascular involvement in extremity soft tissue sarcoma.

Advances in adjuvant treatment protocols and improvements in imaging techniques have helped improve the limb-salvage rate for extremity soft tissue sarcomas to approximately 95%. Moreover, improvements in operative techniques have enabled successful limb-salvage surgery to be performed even in the face of vascular invasion or encasement by tumor. En bloc resection of major vascular structures with the tumor and reconstruction with reversed saphenous vein grafts, femoral venous grafts, or synthetic grafts has proved to be a feasible option in limb-salvage surgery.

Peripheral nerve considerations in the management of extremity soft tissue sarcomas.

Evaluation of peripheral nerves, both clinically and with imaging, is critical in the evaluation of patients with extremity soft tissue sarcomas. If an essential peripheral nerve is felt to be adjacent to a soft tissue sarcoma but not circumferentially surrounded, it can usually be salvaged using the technique of epineural dissection in the setting of adjuvant radiation. If, however, a critical nerve is circumferentially involved with tumor, it must be sacrificed for the sake of local control.

Parathyroid hormone-related protein regulates glioma-associated oncogene transcriptional activation: lessons learned from bone development and cartilage neoplasia.

Hedgehog and parathyroid hormone-related protein (PTHrP) signaling play important roles regulating the differentiation of chondrocytes, which form the template for growing bone. By studying the interaction of the pathways in normal and neoplastic growth-plate chondrocytes (from enchondromas, a benign cartilage tumor), an unexpected direct regulation of hedgehog-mediated transcriptional activation by parathyroid hormone-related protein was uncovered. This regulation acts through the processing of the hedgehog-activated transcription factor, glioma-associated oncogene-three (Gli3).

Patched-one or smoothened gene mutations are infrequent in chondrosarcoma.

Constitutive hedgehog signaling has been implicated in the tumorigenesis of cartilaginous neoplasia; however, a common mutational mechanism remains unknown. Some tumors exhibiting hedgehog pathway activation such as basal cell cancer frequently harbor PATCHED-ONE (PTCH-1) or SMOOTHENED (SMO) gene mutations. We therefore asked whether mutations of the hedgehog receptor genes PTCH-1 or SMO occur in cartilage tumors.

Proliferative activity (ki-67 expression) and outcome in high grade osteosarcoma: a study of 27 cases.

Purpose. Although pre-operative chemotherapy has improved the prognosis for individuals with osteosarcoma, approximately 40% of patients will die of their disease.The aim of this study was to quantitate proliferative activity in high grade osteosarcomas and to determine whether proliferation is a prognostic factor.

Symptoms and their Relationship to Disability Following Treatment for Lower Extremity Tumours.

Purpose. The aims of this study were to describe the symptoms experienced by patients in the first year following treatment for lower extremity sarcoma by limb conservation and to describe the relationship between symptoms and physical disability.Subjects.

A comparison of outcome of osteoarticular allograft reconstruction and shoulder arthrodesis following resection of primary tumours of the proximal humerus.

Purpose. The purpose of this study was to compare the oncologic, reconstructive and functional outcomes of patients who underwent osteoarticular allograft reconstruction with those who underwent arthrodesis for a primary malignant bone tumour of the proximal humerus.Patients.

Oncologic and functional outcome of scapular chondrosarcoma.

Background: The scapula is a common site for chondrosarcoma to occur. There has been disagreement between recent studies documenting the oncologic outcomes in patients with chondrosarcoma of the scapula. The purpose of this study was to investigate both the oncologic and functional outcomes of patients presenting to a large oncology center with primary chondrosarcoma of the scapula.

Natural DNA variation at candidate loci is associated with potato chip color, tuber starch content, yield and starch yield.

Complex characters of plants such as starch and sugar content of seeds, fruits, tubers and roots are controlled by multiple genetic and environmental factors. Understanding their molecular basis will facilitate diagnosis and combination of superior alleles in crop improvement programs ("precision breeding"). Association genetics based on candidate genes is one approach toward this goal.

Giant cell tumor of bone express p63.

p63 contributes to skeletal development and tumor formation; however, little is known regarding its activity in the context of bone and soft tissue neoplasms. The purpose of this study was to investigate p63 expression in giant cell tumor of bone and to determine whether it can be used to discriminate between other giant cell-rich tumors. Seventeen cases of giant cell tumor of bone were examined to determine the cell type expressing p63 and identify the isoforms present.

Free tissue transfer and deep vein thrombosis.

Reconstruction of the post-oncologic defect of the lower limb frequently requires free tissue transfer and these often extensive bone and soft tissue resections can occasionally be compounded by the presence of a deep venous thrombosis (DVT). We describe two patients in whom free tissue transfer was attempted, following extensive resection of a sarcoma in the thigh. Both patients had been diagnosed with DVT prior to surgery and received therapeutic low molecular weight heparin preoperatively.

Two-stage revision of infected uncemented lower extremity tumor endoprostheses.

We reviewed our experience with 2-stage revision of uncemented Kotz Modular Femoral and Tibial Replacement System prostheses from 1989 to 2004. A total of 180 lower extremity tumor prostheses were inserted, 15 of which underwent removal of the prosthesis for infection. Eleven patients underwent subsequent second-stage revision, and 4 underwent amputation.

Side population cells isolated from mesenchymal neoplasms have tumor initiating potential.

Although many cancers are maintained by tumor-initiating cells, this has not been shown for mesenchymal tumors, in part due to the lack of unique surface markers that identify mesenchymal progenitors. An alternative technique to isolate stem-like cells is to isolate side population (SP) cells based on efflux of Hoechst 33342 dye. We examined 29 mesenchymal tumors ranging from benign to high-grade sarcomas and identified SP cells in all but six samples.

Studies of the in vivo radiosensitivity of human skin fibroblasts.

Background And Purpose: To examine the radiosensitivity of skin cells obtained directly from the irradiated skin of patients undergoing fractionated radiation treatment prior to surgery for treatment of soft tissue sarcoma (STS) and to determine if there was a relationship with the development of wound healing complications associated with the surgery post-radiotherapy.

Methods: Micronucleus (MN) formation was measured in cells (primarily dermal fibroblasts) obtained from human skin at their first division after being removed from STS patients during post-radiotherapy surgery (2-9 weeks after the end of the radiotherapy). At the time of radiotherapy (planned tumor dose - 50Gy in 25 daily fractions) measurements were made of surface skin dose at predetermined marked sites.

Opportunities for improving the therapeutic ratio for patients with sarcoma.

Sarcomas are mesenchymal cancers, which, in many cases, have distinctive molecular features. Limb-sparing surgery delivered at specialised sarcoma centres as part of a multidisciplinary approach has become the standard treatment for most patients and usually provides excellent local control. Preoperative treatment with chemotherapy is most common for patients with bone sarcomas.

Functional outcomes after treatment of aggressive tumors in the distal radius.

We aimed to determine whether wide excision and radiocarpal arthrodesis in patients with aggressive tumors of the distal radius resulted in more significant functional deficit than joint salvage procedures. We compared functional outcomes, surgical complications, and local tumor relapse in 33 consecutive patients. Fourteen patients initially had joint-sparing procedures, whereas 19 underwent wide resection and arthrodesis.

Joint salvage for pathologic fracture of giant cell tumor of the lower extremity.

Pathologic fracture through giant cell tumor is thought to be associated with higher rates of recurrence and poor functional outcome. We compared patients with and without pathologic fracture through giant cell tumor of weightbearing long bones. We retrospectively reviewed 139 patients with giant cell tumor of weightbearing long bones with (n = 43) and without (n = 96) pathologic fracture at presentation; the two groups had similar demographics.

COPS3 amplification and clinical outcome in osteosarcoma.

Background: Amplification of several genes that map to a region of chromosome 17p11.2, including COPS3, was observed in high-grade osteosarcoma. These genes were also shown to be overexpressed and may be involved in osteosarcoma tumorigenesis.

PTHrP regulates growth plate chondrocyte differentiation and proliferation in a Gli3 dependent manner utilizing hedgehog ligand dependent and independent mechanisms.

Growth plate chondrocytes undergo a tightly regulated process of differentiation, allowing for the longitudinal growth of bones. Although it is known that parathyroid hormone related protein (PTHrP) and Indian hedgehog regulate the differentiation of growth plate chondrocytes, how these pathways interact to regulate chondrocyte development is not fully elucidated. We examined how the interaction between PTHrP and the hedgehog activated transcription factors, Gli2 and Gli3, regulates growth plate chondrocyte differentiation and proliferation.

Radiation planning comparison for superficial tissue avoidance in radiotherapy for soft tissue sarcoma of the lower extremity.

Purpose: Three types of preoperative radiotherapy (RT) plans for extremity soft tissue sarcoma were compared to determine the amount of dose reduction possible to the planned surgical skin flaps required for tumor resection and wound closure, without compromising target coverage.

Methods And Materials: Twenty-four untreated patients with large, deep, lower extremity STS treated with preoperative RT and limb salvage surgery had their original conventional treatment plans re-created. The same clinical target volume was used for all three plans.

Does the method of treatment affect the outcome in soft-tissue sarcomas of the adductor compartment?

We have investigated the significance of the method of treatment on the oncological and functional outcomes and on the complications in 184 patients with soft-tissue sarcomas of the adductor compartment managed at three international centres. The overall survival at five years was 65% and was related to the grade at diagnosis and the size of the tumour. There was no difference in overall survival between the three centres.