Galanin and galanin receptor expression in neuroblastic tumours: correlation with their differentiation status

Neuroblastoma and its benign differentiated counterpart, ganglioneuroma, are paediatric neuroblastic tumours arising in the sympathetic nervous system. Their broad spectrum of clinical virulence is mainly related to heterogeneous biologic background and tumour differentiation. Neuroblastic tumours synthesize various neuropeptides acting as neuromodulators. Previous studies suggested that galanin plays a role in sympathetic tissue where it could be involved in differentiation and development. We investigated the expression and distribution of galanin and its three known receptors (Gal-R1, Gal-R2, Gal-R3) in 19 samples of neuroblastic tumours tissue by immunohistochemistry, in situ hybridization and fluorescent-ligand binding. This study provides clear evidence for galanin and galanin receptor expression in human neuroblastic tumours. The messengers coding for galanin, Gal-R1 and -R3 were highly expressed in neuroblastoma and their amount dramatically decreased in ganglioneuroma. In contrast, Gal-R2 levels remained unchanged. Double labelling studies showed that galanin was mainly co-expressed with its receptors whatever the differentiation stage. In neuroblastic tumours, galanin might promote cell-survival or counteract neuronal differentiation through the different signalling pathways mediated by galanin receptors. Finally, our results suggest that galanin influences neuroblastoma growth and development as an autocrine/paracrine modulator. These findings suggest potential critical implications for galanin in neuroblastic tumours development

Advances in the treatment of prolactinomas

Prolactinomas account for approximately 40% of all pituitary adenomas and are an important cause of hypogonadism and infertility. The ultimate goal of therapy for prolactinomas is restoration or achievement of eugonadism through the normalization of hyperprolactinemia and control of tumor mass. Medical therapy with dopamine agonists is highly effective in the majority of cases and represents the mainstay of therapy. Recent data indicating successful withdrawal of these agents in a subset of patients challenge the previously held concept that medical therapy is a lifelong requirement. Complicated situations, such as those encountered in resistance to dopamine agonists, pregnancy, and giant or malignant prolactinomas, may require multimodal therapy involving surgery, radiotherapy, or both. Progress in elucidating the mechanisms underlying the pathogenesis of prolactinomas may enable future development of novel molecular therapies for treatment-resistant cases. This review provides a critical analysis of the efficacy and safety of the various modes of therapy available for the treatment of patients with prolactinomas with an emphasis on challenging situations, a discussion of the data regarding withdrawal of medical therapy, and a foreshadowing of novel approaches to therapy that may become available in the future