19 research outputs found
NF1 deletion generates multiple subtypes of soft-tissue sarcoma that respond to mek inhibition
Soft-tissue sarcomas are a heterogeneous group of tumors arising from connective tissue. Recently, mutations in the neurofibromin 1 (NF1) tumor suppressor gene were identified in multiple subtypes of human soft-tissue sarcomas. To study the effect of NF1 inactivation in the initiation and progression of distinct sarcoma subtypes, we have developed a novel mouse model of temporally and spatially restricted NF1-deleted sarcoma. To generate primary sarcomas, we inject adenovirus containing Cre recombinase into NF1 <sup>flox/flox</sup>; Ink4a/Arf<sup>flox/flox</sup> mice at two distinct orthotopic sites: intramuscularly or in the sciatic nerve. The mice develop either high-grade myogenic sarcomas or malignant peripheral nerve sheath tumor (MPNST)-like tumors, respectively. These tumors reflect the histologic properties and spectrum of sarcomas found in patients. To explore the use of this model for preclinical studies, we conducted a study of mitogen-activated protein kinase (MAPK) pathway inhibition with the MEK inhibitor PD325901. Treatment with PD325901 delays tumor growth through decreased cyclin D1 mRNA and cell proliferation. We also examined the effects of MEK inhibition on the native tumor stroma and find that PD325901 decreases VEGFalpha expression in tumor cells with a corresponding decrease in microvessel density. Taken together, our results use a primary tumor model to show that sarcomas can be generated by loss of NF1 and Ink4a/Arf, and that these tumors are sensitive to MEK inhibition by direct effects on tumor cells and the surrounding microenvironment. These studies suggest that MEK inhibitors should be further explored as potential sarcoma therapies in patients with tumors containing NF1 deletion. 2013 American Association for Cancer Researc
The Vascularized Fibular Graft in the Treatment of Osteonecrosis: Data, Dogma, and Controversies
Laparoscopic treatment of abdominal unicentric castleman’s disease: a case report and literature review
Castleman's disease is a rare lymphoproliferative disorder of unknown etiology that most commonly presents as a mediastinal nodal mass. It is exceptionally uncommon for Castleman's disease to present in the mesentery and, only 53 cases have ever been described in the literature. Standard treatment for this lymphoproliferative disorder involving a single node is a complete "en bloc" surgical resection which has proven to be a curative approach in almost all cases without recurrence after 20 years of follow up. All 53 reported cases of mesenteric Castleman's disease, except one, were treated with laparotomy