Diffusing alpha-emitters radiation therapy in combination with temozolomide or bevacizumab in human glioblastoma multiforme xenografts.

Glioblastoma multiforme (GBM) is at present an incurable disease with a 5-year survival rate of 5.5%, despite improvements in treatment modalities such as surgery, radiation therapy, chemotherapy [e.g.

Diffusing Alpha-Emitters Radiation Therapy Promotes a Proimmunogenic Tumor Microenvironment and Synergizes With Programmed Cell Death Protein 1 Blockade.

Purpose: Diffusing alpha-emitters Radiation Therapy (DaRT) releases alpha-emitting atoms into the tumor microenvironment. The treatment effectively ablates human and mice xenografts and shows 100% response rates in skin or head and neck squamous cell carcinoma patients. DaRT induces specific and systemic antitumor immune activation and synergizes with immune stimulation and modulation in mice.

WWOX and p53 Dysregulation Synergize to Drive the Development of Osteosarcoma.

Osteosarcoma is a highly metastatic form of bone cancer in adolescents and young adults that is resistant to existing treatments. Development of an effective therapy has been hindered by very limited understanding of the mechanisms of osteosarcomagenesis. Here, we used genetically engineered mice to investigate the effects of deleting the tumor suppressor Wwox selectively in either osteoblast progenitors or mature osteoblasts.

Tumor Suppressor WWOX inhibits osteosarcoma metastasis by modulating RUNX2 function.

Osteosarcoma (OS) is among the most frequently occurring primary bone tumors, primarily affecting adolescents and young adults. This malignant osteoid forming tumor is characterized by its metastatic potential, mainly to lungs. We recently demonstrated that WW domain-containing oxidoreductase (WWOX) is frequently inactivated in human OS and that WWOX restoration in WWOX-negative OS cells suppresses tumorigenicity.

Conditional inactivation of the mouse Wwox tumor suppressor gene recapitulates the null phenotype.

WW domain-containing oxidoreductase (WWOX) is highly conserved in both human and murine. WWOX spans the second most common human chromosomal fragile site, FRA16D, and is commonly inactivated in multiple human cancers. Modeling WWOX inactivation in mice revealed a complex phenotype including postnatal lethality, defects in bone metabolism and steroidogenesis and tumor suppressor function resulting in osteosarcomas.

miRNA signatures associate with pathogenesis and progression of osteosarcoma.

Osteosarcoma remains a leading cause of cancer death in adolescents. Treatment paradigms and survival rates have not improved in two decades. Driving the lack of therapeutic inroads, the molecular etiology of osteosarcoma remains elusive.

Role of the WWOX tumor suppressor gene in bone homeostasis and the pathogenesis of osteosarcoma.

Osteosarcoma is the most common primary bone malignancy in children with unknown etiology and often with poor clinical outcome. In recent years, a critical role has emerged for the WW domain-containing oxidoreductase (WWOX) in osteosarcoma and bone biology. WWOX is a tumor suppressor that is deleted or attenuated in most human tumors.

Frequent attenuation of the WWOX tumor suppressor in osteosarcoma is associated with increased tumorigenicity and aberrant RUNX2 expression.

The WW domain-containing oxidoreductase (WWOX) is a tumor suppressor that is deleted or attenuated in most human tumors. Wwox-deficient mice develop osteosarcoma (OS), an aggressive bone tumor with poor prognosis that often metastasizes to lung. On the basis of these observations, we examined the status of WWOX in human OS specimens and cell lines.

The CD4+ T-cell epitope-binding register is a critical parameter when generating functional HLA-DR tetramers with promiscuous peptides.

Detection of CD4(+) T cells specific for tumor-associated antigens is critical to investigate the spontaneous tumor immunosurveillance and to monitor immunotherapy protocols in patients. We investigated the ability of HLA-DR 1101 multimers to detect CD4(+) T cells specific for three highly promiscuous MAGE-A3 derived peptides: MAGE-A3(191-205) (p39), MAGE-A3(281-295) (p57) and MAGE-A3(286-300) (p58). Tetramers stained specific CD4(+) T cells only when loaded with p39, although all peptides activated the specific T cells when presented by plastic-bound HLA-DR 1101 monomers.

WWOX: its genomics, partners, and functions.

The WW domain-containing oxidoreductase (WWOX) spans one of the most active common fragile sites (CFSs) involved in cancer, FRA16D. WWOX encodes a 46-kDa protein that contains two N-terminal WW domains and a central short-chain dehydrogenase/reductase (SDR) domain. Through its WW domain, Wwox interacts with its partners and modulates their functions.

Use of MHC class II tetramers to investigate CD4+ T cell responses: problems and solutions.

MHC-class I tetramers technology enabled the characterization of peptide-specific T cells at the single cell level in a variety of studies. Several laboratories have also developed MHC-class II multimers to characterize Ag-specific CD4+ T cells. However, the generation and use of MHC-class II multimers seems more problematic than that of MHC-I multimers.