Sonic Hedgehog pathway is upregulated in adamantinomatous craniopharyngiomas.

OBJECTIVES: Pituitary stem cells play a role in the oncogenesis of human adamantinomatous craniopharyngiomas (aCPs). We hypothesized that crosstalk between the Wnt/ß-catenin and Sonic Hedgehog (SHH) pathways, both of which are important in normal pituitary development, would contribute to the pathogenesis of aCPs. DESIGN: To explore the mRNA and protein expression of components of the SHH signaling pathway in aCPs and their relationship with the identification of CTNNB1/ß-catenin mutations and patients outcomes. PATIENTS AND METHODS: In 18 aCP samples, CTNNB1 was sequenced, and the mRNA expression levels of SHH pathway members (SHH, PTCH1, SMO, GLI1, GLI2, GLI3, and SUFU) and SMO, GLI1, GLI3, SUFU, ß-catenin, and Ki67 proteins were evaluated by quantitative real-time PCR and immunohistochemistry respectively. Anterior normal pituitaries were used as controls. Associations between molecular findings and clinical data were analyzed. RESULTS: The aCPs presented higher mRNA expression of SHH (+400-fold change (FC); P<0.01), GLI1 (+102-FC; P<0.001), and GLI3 (+5.1-FC; P<0.01) than normal anterior pituitaries. Longer disease-free survival was associated with low SMO and SUFU mRNA expression (P<0.01 and P=0.02 respectively). CTNNB1/ß-catenin mutations were found in 47% of the samples. aCPs with identified mutations presented with higher mRNA expression of SMO and GLI1 (+4.3-FC; P=0.02 and +10.2-FC; P=0.03 respectively). SMO, GLI1, GLI3, and SUFU staining was found in 85, 67, 93, and 64% of the samples respectively. Strong GLI1 and GLI3 staining was detected in palisade cells, which also labeled Ki67, a marker of cell proliferation. CONCLUSIONS: The upregulation of SHH signaling occurs in aCPs. Thus, activation of Wnt/ß-catenin and SHH pathways, both of which are important in pituitary embryogenesis, appears to contribute to the pathogenesis of aCP.

Interindividual glucocorticoid sensitivity in young healthy subjects: the role of glucocorticoid receptor alpha and beta isoforms ratio.

Only few studies have addressed the interindividual variation and tissue specificity of glucocorticoid (GC) sensitivity in healthy individuals, a phenomenon observed in pathological conditions. Alternative splicing of the glucocorticoid receptor (GR) produces alpha and beta isoforms. GRbeta has dominant-negative effects on hormone-induced GRalpha effects, and an increased expression of the GRbeta has been associated with glucocorticoid resistance. We determined, using a simple, rapid, and accurate Real-Time PCR assay, the individual mRNAs expression of GRalpha and GRbeta in 26 normal subjects (mean+/-SE, age 30+/-6 years; 12 males and 14 females), in order to evaluate the role of these isoforms in glucocorticoid sensitivity in health. Glyceraldehydes-3-phosphate dehydrogenase (GAPDH) was used as a housekeeper gene. GRalpha/GAPDH, GRbeta/GAPDH and GRalpha/GRbeta ratios showed a normal distribution. We observed a higher expression of GRalpha compared to GRbeta and an interindividual variability in the GRalpha, GRbeta, and GAPDH gene expressions in the young healthy population. In addition, no correlation was observed between GRalpha/GRbeta ratio and the dexamethasone (DEX) doses needed to suppress plasma cortisol, GRalpha/GRbeta ratio and the concentration of DEX that caused inhibition of Con-A stimulated cell proliferation, and GRalpha/GRbeta ratio and the affinity of GR (Kd) of each subject. Therefore, the variability of GC sensitivity observed in normal subjects can not be ascribed to the variation in the GRalpha and GRbeta expression.

[Fragmentation needs integration: the patient and his nursing care]. / "Frammentazione e bisogno di integrazione: l'uomo malato e il "prendersi cura" infermieristco".

The Author analyses the psyco-physical conditions prevailing during illness and hospitalization: from the alterations taking place in the anti-stimulus barriers, to the damages in the oneself perception as a whole. Being at the same time a psychologist and a patient, the A focalizes the value she believes the most specific one of the nursing profession: to care for the body means to care for the person, while the awareness of the suffering conditions means to care for the fundamental needs of reassurance, psycho-physical integration and interpersonal communication.