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Here, we report for the first time cell-permeable and biocompatible polymeric nanoparticles consisting of a polymer conjugated to a near-infrared (NIR) fluorescence (Cy5.5)-linked effector caspase-specific peptide. The close spatial proximity of the NIR fluorochromes in polymeric nanoparticles results in an autoquenched state, but polymer nanoparticles give(More)
Multiple endocrine neoplasia (MEN) syndromes are characterized by tumors involving two or more endocrine glands. Two MEN syndromes have long been known: MEN1 and MEN2,caused by germline mutations in MEN1 or RET, respectively. Recently, mutations in CDKN1B,encoding the cyclin-dependent kinase (Cdk) inhibitor p27, were identified in patients having a(More)
Germline mutations in p27(kip1) are associated with increased susceptibility to multiple endocrine neoplasias (MEN) both in rats and humans; however, the potential role of common polymorphisms of this gene in endocrine tumor susceptibility and tumorigenesis remains mostly unrecognized. To assess the risk associated with polymorphism rs2066827 (p27-V109G),(More)
OBJECTIVE To date, no evidence of robust genotype-phenotype correlation or disease modifiers for multiple endocrine neoplasia type 1 (MEN1) syndrome has been described, leaving the highly variable clinical presentation of patients unaccounted for. DESIGN As the CDKN1B (p27) gene causes MEN4 syndrome and it is transcriptionally regulated by the product of(More)
Constitutive activation of the phosphatidylinositol 3-kinase (PI3K)/AKT/mTOR signaling cascade occurs in a variety of human malignancies, where it sustains tumor cell proliferation and survival. Pharmacologic blockade of this pathway exerts antineoplastic activity by triggering apoptosis and/or cell-cycle arrest. Pituitary adenomas show activation of the(More)
p27Kip1 (p27) is an important negative regulator of the cell cycle and a putative tumor suppressor. The finding that a spontaneous germline frameshift mutation in Cdkn1b (encoding p27) causes the MENX multiple endocrine neoplasia syndrome in the rat provided the first evidence that Cdkn1b is a tumor susceptibility gene for endocrine tumors. Noteworthy,(More)
X-linked acrogigantism (X-LAG) is a new syndrome of pituitary gigantism, caused by microduplications on chromosome Xq26.3, encompassing the gene GPR101, which is highly upregulated in pituitary tumors. We conducted this study to explore the clinical, radiological, and hormonal phenotype and responses to therapy in patients with X-LAG syndrome. The study(More)
PURPOSE Novel therapeutic approaches are needed to improve the postoperative management of residual nonfunctioning pituitary adenomas (NFPA), given their high relapse rate. Here, we evaluated the antitumor efficacy of the dual PI3K/mTOR inhibitor NVP-BEZ235 in the only available model of spontaneous NFPAs (MENX rats). EXPERIMENTAL DESIGN Organotypic(More)
Gonadotroph pituitary adenomas (GPAs) often present as invasive macroadenomas not amenable to complete surgical resection. Radiotherapy is the only post-operative option for patients with large invasive or recurrent lesions. No medical treatment is available for these patients. The somatostatin analogs (SSAs) octreotide and lanreotide that preferentially(More)
Familial isolated pituitary adenoma (FIPA) occurs in families and is unrelated to multiple endocrine neoplasia type 1 and Carney complex. Mutations in AIP account only for 15-25% of FIPA families. CDKN1B mutations cause MEN4 in which affected patients can suffer from pituitary adenomas. With this study, we wanted to assess whether mutations in CDKN1B occur(More)