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View the Table of Contents for the April 1 issue of Cancer Research.
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The highly aggressive muscle cancer alveolar rhabdomyosarcoma (ARMS) is one of the most common soft tissue sarcomas of childhood; yet it is difficult to cure when metastatic despite over 35 years of cooperative trials. Nishijo and colleagues show that a genetically engineered mouse model of ARMS shares the natural history and pathological features of the human disease. The authors also show that the pathognomonic, translocation-mediated Pax3:Fkhr fusion gene is overexpressed relatively late in disease progression. With an eye toward therapeutics, the authors employ a cross-species analysis not only to define a Pax3:Fkhr gene expression signature, but also to identify potential targets of molecular therapeutics.
Canova et al. Page 2956 Cancers of the upper aerodigestive tract (UADT) account for about 10% of cancers worldwide and 6% of all new cancers in Europe. Canova and colleagues analyzed 115 single nucleotide polymorphisms (SNPs) from 62 a priori–selected genes from patient samples obtained from the ARCAGE study, which includes 10 European countries comprising 1,500 UADT cases and 1,500 controls. Notable results (P trend < 0.01) were identified for SNPs in CYP2A6, MDM2, TNF, and GASC1, pointing to potentially relevant pathways for these cancers. Additional detailed characterization of these pathways, as well as more detailed genome-wide studies of head and neck cancer, will elucidate the genetic susceptibility of these cancers.
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Uluçkan et al. Page 3196 CD47 is an atypical member of the immunoglobulin superfamily that interacts with and activates β3 integrins. β3 integrin–/– mice are protected from bone metastasis, but the role of CD47 in skeletal homeostasis and bone metastasis is not known. Uluçkan and colleagues report that CD47–/– mice had increased bone mass and defective osteoclast function in vivo, with high doses of RANKL and inhibition of nitric oxide synthase rescuing the defect. In a model of tumor metastasis to bone, bone tumor burden was decreased in the CD47–/– mice compared to wild-type controls. These data demonstrate that CD47 regulates osteoclastogenesis, in part, via regulation of nitric oxide production, and its disruption leads to a decrease in tumor bone metastasis.
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