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Metastatic cancers, once established, are the primary cause of mortality associated with cancer. Previously, we used a genomic approach to identify metastasis-associated genes in cancer. From this genomic data, we selected ezrin for further study based on its role in physically and functionally connecting the actin cytoskeleton to the cell membrane. In a(More)
PURPOSE It has been observed previously in osteosarcoma (OS) that the degree of necrosis of the resected primary tumor following a period of preoperative chemotherapy is predictive of subsequent event-free survival (EFS). The aim of this study was to determine if more intensive preoperative chemotherapy would increase the proportion of patients with a good(More)
Osteosarcoma is the most common malignant bone tumor in children and adolescents. Survival for these patients was poor with the use of surgery and/or radiotherapy. The introduction of multi-agent chemotherapy dramatically improved the outcome for these patients and the majority of modern series report 3-year disease-free survival of 60%-70%. This paper(More)
For patients with osteosarcoma, the use of chemotherapy has improved survival from 11% with surgical resection alone in the 1960s, to 70% by the mid-1980s. However, survival has since plateaued, despite advances in anticancer therapy. Elucidation of the mechanisms of chemoresistance and implementation of strategies to overcome chemoresistance will likely be(More)
PURPOSE EWS-FLI1 fusion type, p53 mutation, and homozygous deletion of p16/p14ARF have each been shown to be prognostically significant in Ewing sarcoma (ES). We provide the first combined prognostic analysis of these three molecular parameters in ES. PATIENTS AND METHODS We studied 60 patients with ES (stage: localized in 54, metastatic in six). All(More)
There are two telomere maintenance mechanisms (TMMs) in human tumors, telomerase activation (TA) and, more rarely, the process termed alternative lengthening of telomeres (ALT). Unlike most carcinomas, sarcomas, including osteosarcomas (OS), have been reported to display TA and ALT in more balanced proportions and, thus, present an opportunity to examine(More)
Despite significant advancements in the diagnosis and treatment of osteosarcoma to date, overall survival has remained relatively constant for over 2 decades. The challenge in osteosarcoma stems from the extreme variability from one tumor to the next, making it unlikely that a single target approach would be able to address all or even a majority of(More)
The purpose of this review was to determine whether imatinib mesylate (STI571, Gleevec) has a role in the treatment of osteosarcoma. The expression of platelet-derived growth factor (PDGF) receptor and its ligand was examined in a panel of surgical specimens obtained from 54 osteosarcoma patients, and then the expression was compared with prognosis. The(More)
BACKGROUND Sorafenib is an inhibitor of multiple kinases (e.g., VEGF receptors, PDGFR, FLT3, RET, BRAF, KIT) and is approved by FDA for treatment of two adult cancers. The activity of sorafenib was evaluated against the PPTP's in vitro and in vivo panels. PROCEDURES Sorafenib was evaluated against the PPTP in vitro panel using 96-hr exposure at(More)
PURPOSE In osteosarcoma, prognostic factors at diagnosis other than clinical stage have not been clearly identified. The aim of this study was to determine whether human epidermal growth factor receptor 2 (HER2)/erbB-2, p-glycoprotein, or p53 expression correlated with histologic response to preoperative chemotherapy or event-free survival. PATIENTS AND(More)