title: Does cyclic guanosine monophosphate induce autophagy in thyroid malignant carcinoma through down-regulation of cyclic guanosine monophosphate phosphodiesterase?
abstract: The aim of this study was to evaluate whether or not the expression of cGMP- phosphodiesterases (cGMP-PDE) varies in different thyroid pathologies and to elucidate the relationship between the expression of cGMP-PDE, cGMP, and autophagy. Fifty-four thyroid biopsy samples, excised to perform the biopsy, were split into two parts and randomly assigned: one part was microscopically examined and histological classified, and the other was frozen and analysed in order to evaluate the cGMP-PDE activity. Intracellular cGMP was also measured. A strong expression of intracellular cGMP and cGMP-PDE activity was observed in carcinoma in respect to controls and benign pathologies. The level of cGMP-PDE in papillary carcinoma without lymph node involvement (N-) was approximately four-fold higher compared to those with lymph node invasion (N±). On the contrary, the cGMP was one and a half times higher in N± than N-. Our results are promising, although further epigenetical studies are needed to confirm this association. A correlation between the cGMP-degrading activity and the severity of thyroid pathology has been shown. The decrease of cGMP-PDE and the increase of cGMP in N± papillar carcinoma could be an autophagic stimulus, a defence mechanism of the body, against the cancer that is expanding and invading other tissues and organs.
authors.affiliation: Laboratory of Medical Chemistry and Dental Materials, Department of Medical, Oral and Biotechnological Sciences, University G. dAnnunzio, Chieti, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Spoto
authors.affiliation: Laboratory of Medical Chemistry and Dental Materials, Department of Medical, Oral and Biotechnological Sciences, University G. dAnnunzio, Chieti, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Esposito
authors.affiliation: Laboratory of Medical Chemistry and Dental Materials, Department of Medical, Oral and Biotechnological Sciences, University G. dAnnunzio, Chieti, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Santoleri
authors.affiliation: Anatomy and Histopathology, Dental School, Polytechnic University of Marche, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Rubini
authors.affiliation: Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland.
authors.forename: A W S
authors.initials: AW
authors.lastname: Rutjes
authors.affiliation: Anatomy and Histopathology, Dental School, Polytechnic University of Marche, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Fioroni
authors.affiliation: Laboratory of Medical Chemistry and Dental Materials, Department of Medical, Oral and Biotechnological Sciences, University G. dAnnunzio, Chieti, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Ferrante
authors.affiliation: Laboratory of Medical Chemistry and Dental Materials, Department of Medical, Oral and Biotechnological Sciences, University G. dAnnunzio, Chieti, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Petrini
mesh_terms: D000328:Adult; D001343:Autophagy; D006152:Cyclic GMP / Q000032:analysis / Q000502:physiology*; D054678:Cyclic Nucleotide Phosphodiesterases, Type 2 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015536:Down-Regulation; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D013961:Thyroid Gland / Q000473:pathology; D013964:Thyroid Neoplasms / Q000473:pathology*
chemical_list: D054678:Cyclic Nucleotide Phosphodiesterases, Type 2; D006152:Cyclic GMP