Search

Your search keyword '"Ambrosio MR"' showing total 289 results
Start Over Author "Ambrosio MR"
289 results on '"Ambrosio MR"'

3. Position statement for clinical practice: prolactin-secreting tumors

Author

Cozzi, R, Ambrosio, Mr, Attanasio, R, Battista, C, Bozzao, A, Caputo, M, Ciccarelli, E, De Marinis, L, De Menis, E, Faustini Fustini, M, Grimaldi, F, Lania, A, Lasio, G, Logoluso, F, Losa, M, Maffei, P, Milani, D, Poggi, M, Zini, M, Katznelson, L, Luger, A, and Poiana, C.

Published
2022

5. PPAR gamma Delta 5, a Naturally Occurring Dominant-Negative Splice Isoform, Impairs PPAR gamma Function and Adipocyte Differentiation

Author

Aprile M, Cataldi S, Ambrosio MR, D'Esposito V, Lim K, Dietrich A, Bluher M, Savage DB, Formisano P, Ciccodicola A, and Costa V

Subjects
lipids (amino acids, peptides, and proteins), PPAR gamma Delta 5, adipocyte differentiation, adipose tissue, alternative splicing, dominant-negative isoform, insulin resistance, obesity
Abstract

Peroxisome-proliferator-activated receptor ? (PPAR?) regulates glucose and lipid homeostasis, insulin signaling, and adipocyte differentiation. Here, we report the skipping of exon 5 as a legitimate splicing event generating PPAR??5, a previously unidentified naturally occurring truncated isoform of PPAR?, which lacks the entire ligand-binding domain. PPAR??5 is endogenously expressed in human adipose tissue and, during adipocyte differentiation, lacks ligand-dependent transactivation ability and acts as a dominant-negative isoform reducing PPAR? activity. Ligand-mediated PPAR? activation induces exon 5 skipping in a negative feedback loop, suggesting alternative splicing as a mechanism regulating PPAR? activity. PPAR??5 overexpression modifies the PPAR?-induced transcriptional network, significantly impairing the differentiation ability of adipocyte precursor cells. Additionally, PPAR??5 expression in subcutaneous adipose tissue positively correlates with BMI in two independent cohorts of overweight or obese and type 2 diabetic patients. From a functional perspective, PPAR??5 mimics PPARG dominant-negative mutated receptors, possibly contributing to adipose tissue dysfunction. These findings open an unexplored scenario in PPARG regulation and PPAR?-related diseases.

Published
2018

6. Real-world study of everolimus in advanced progressive neuroendocrine tumors

Author

Panzuto F, Rinzivillo M, Fazio N, de Braud F, Luppi G, Zatelli MC, Lugli F, Tomassetti P, Riccardi F, Nuzzo C, Brizzi MP, Faggiano A, Zaniboni A, Nobili E, Pastorelli D, Cascinu S, Merlano M, Chiara S, Antonuzzo L, Funaioli C, Spada F, Pusceddu S, Fontana A, Ambrosio MR, Cassano A, Campana D, Cartenì G, Appetecchia M, Berruti A, Colao A, Falconi M, Panzuto, F, Rinzivillo, M, Fazio, N, de Braud, F, Luppi, G, Zatelli, Mc, Lugli, F, Tomassetti, P, Riccardi, F, Nuzzo, C, Brizzi, Mp, Faggiano, A, Zaniboni, A, Nobili, E, Pastorelli, D, Cascinu, S, Merlano, M, Chiara, S, Antonuzzo, L, Funaioli, C, Spada, F, Pusceddu, S, Fontana, A, Ambrosio, Mr, Cassano, A, Campana, D, Cartenì, G, Appetecchia, M, Berruti, A, Colao, A, and Falconi, M

Published
2015

7. INVOLVEMENT OF HYPOTHALAMUS AUTOIMMUNITY IN PATIENTS WITH AUTOIMMUNE HYPOPITUITARISM: ROLE OF ANTIBODIES TO HYPOTHALAMIC CELLS

Author

De Bellis, A, Sinisi, Aa, Pane, E, Dello Iacovo, A, Bellastella, G, Di Scala, G, Falorni, A, Giavoli, C, Gasco, V, Giordano, R, Ambrosio, Mr, Colao, A, Bizzarro, A, Bellastella, A, Italian Autoimmune Hypophysitis Network Group Arvat, E, Beck Peccoz, P, Betterle, C, Cannavo', Salvatore, Chiovato, L, Delvecchio, M, De Marinis, L, Degli Uberti, E, Ghigo, E, Maghnie, M, Mantero, F, Persani, L, Rotondi, M, Spada, A, Zatelli, M. C., DE BELLIS, Annamaria, Sinisi, Aa, Pane, E, Dello Iacovo, A, Bellastella, Giuseppe, Di Scala, G, Falorni, A, Giavoli, C, Gasco, V, Giordano, R, Ambrosio, Mr, Colao, A, Bizzarro, Antonio, and Bellastella, A.

Subjects
Adult, Male, medicine.medical_specialty, anticorpi anti-ipotalamo, Corticotropin-Releasing Hormone, Hypophysitis, Endocrinology, Diabetes and Metabolism, Clinical Biochemistry, Context (language use), Hypopituitarism, Immunofluorescence, medicine.disease_cause, Biochemistry, Autoimmune Diseases, sindrome poliendocrina autoimmune, Autoimmunity, NO, Cohort Studies, Anticorpi anti-ipofisi, Endocrinology, Adrenocorticotropic Hormone, Antibody Specificity, Seroepidemiologic Studies, Internal medicine, medicine, Humans, antibodies, hypothalamus, health care economics and organizations, Autoantibodies, diabete insipido centrale, Subclinical infection, medicine.diagnostic_test, Human Growth Hormone, business.industry, Biochemistry (medical), medicine.disease, hypophysitis, Diabetes Insipidus, Neurogenic, Cross-Sectional Studies, Diabetes insipidus, Immunology, Autoimmune hypophysitis, Female, business
Abstract

Antipituitary antibodies (APA) but not antihypothalamus antibodies (AHA) are usually searched for in autoimmune hypopituitarism.Our objective was to search for AHA and characterize their hypothalamic target in patients with autoimmune hypopituitarism to clarify, on the basis of the cells stained by these antibodies, the occurrence of autoimmune subclinical/clinical central diabetes insipidus (CDI) and/or possible joint hypothalamic contribution to their hypopituitarism.We conducted a cross-sectional cohort study.Ninety-five APA-positive patients with autoimmune hypopituitarism, 60 without (group 1) and 35 with (group 2) lymphocytic hypophysitis, were studied in comparison with 20 patients with postsurgical hypopituitarism and 50 normal subjects.AHA by immunofluorescence and posterior pituitary function were evaluated; then AHA-positive sera were retested by double immunofluorescence to identify the hypothalamic cells targeted by AHA.AHA were detected at high titer in 12 patients in group 1 and in eight patients in group 2. They immunostained arginine vasopressin (AVP)-secreting cells in nine of 12 in group 1 and in four of eight in group 2. All AVP cell antibody-positive patients presented with subclinical/clinical CDI; in contrast, four patients with GH/ACTH deficiency but with APA staining only GH-secreting cells showed AHA targeting CRH- secreting cells.The occurrence of CDI in patients with lymphocytic hypophysitis seems due to an autoimmune hypothalamic involvement rather than an expansion of the pituitary inflammatory process. To search for AVP antibody in these patients may help to identify those of them prone to develop an autoimmune CDI. The detection of AHA targeting CRH-secreting cells in some patients with GH/ACTH deficiency but with APA targeting only GH-secreting cells indicates that an autoimmune aggression to hypothalamus is jointly responsible for their hypopituitarism.

Published
2012

8. Italian autoimmune hypophysitis network group.Involvement of hypothalamus autoimmunity in patients with autoimmune hypopituitarism:role of antibodies to hypothalamic cells

Author

De Bellis A, Sinisi AA, Pane E, Dello Iacovo A, bellastella G, di Scala G, Falorni A, Giavoli C, Gasco V, Giordano R, Ambrosio MR, Bizzarro A, Bellastella A., COLAO, ANNAMARIA, De Bellis, A, Sinisi, Aa, Pane, E, Dello Iacovo, A, Bellastella, G, di Scala, G, Falorni, A, Giavoli, C, Gasco, V, Giordano, R, Ambrosio, Mr, Colao, Annamaria, Bizzarro, A, and Bellastella, A.

Abstract

Antipituitary antibodies (APA) but not antihypothalamus antibodies (AHA) are usually searched for in autoimmune hypopituitarism.Our objective was to search for AHA and characterize their hypothalamic target in patients with autoimmune hypopituitarism to clarify, on the basis of the cells stained by these antibodies, the occurrence of autoimmune subclinical/clinical central diabetes insipidus (CDI) and/or possible joint hypothalamic contribution to their hypopituitarism.We conducted a cross-sectional cohort study. Ninety-five APA-positive patients with autoimmune hypopituitarism, 60 without (group 1) and 35 with (group 2) lymphocytic hypophysitis, were studied in comparison with 20 patients with postsurgical hypopituitarism and 50 normal subjects. AHA by immunofluorescence and posterior pituitary function were evaluated; then AHA-positive sera were retested by double immunofluorescence to identify the hypothalamic cells targeted by AHA. AHA were detected at high titer in 12 patients in group 1 and in eight patients in group 2. They immunostained arginine vasopressin (AVP)-secreting cells in nine of 12 in group 1 and in four of eight in group 2. All AVP cell antibody-positive patients presented with subclinical/clinical CDI; in contrast, four patients with GH/ACTH deficiency but with APA staining only GH-secreting cells showed AHA targeting CRH- secreting cells. The occurrence of CDI in patients with lymphocytic hypophysitis seems due to an autoimmune hypothalamic involvement rather than an expansion of the pituitary inflammatory process. To search for AVP antibody in these patients may help to identify those of them prone to develop an autoimmune CDI. The detection of AHA targeting CRH-secreting cells in some patients with GH/ACTH deficiency but with APA targeting only GH-secreting cells indicates that an autoimmune aggression to hypothalamus is jointly responsible for their hypopituitarism.

Published
2012

9. Detection of antipituitary and antihypothalamus antibodies to investigate the role of pituitary or hypothalamic autoimmunity in patients with selective idiopathic hypopituitarism

Author

De Bellis, A, Pane, E, Bellastella, G, Sinisi, Aa, Colella, C, Giordano, R, Giavoli, C, Lania, A, Ambrosio, Mr, Di Somma, C, Zatelli, Mc, Arvat, E, Colao, A, Bizzarro, A, Bellastella, A, Italian Autoimmune Hypophysitis Network Study Beck Peccoz, P, Betterle, C, Cannavo', Salvatore, Degli Uberti, E, Ghigo, E, Lombardi, G, Maghnie, M, Mantero, F, Spada, A, Falorni, A, Delvecchio, M, De Marinis, L, Martino, E, Rotondi, M, Chiovato, L., De Bellis, A, Pane, E, Bellastella, G, Sinisi, Aa, Colella, C, Giordano, R, Giavoli, C, Lania, A, Ambrosio, Mr, Di Somma, C, Zatelli, Mc, Arvat, E, Colao, A, Bizzarro, A, Bellastella, A, Beck-Peccoz, P, Betterle, C, Cannavò, S, Degli Uberti, E, Ghigo, E, Lombardi, G, Maghnie, M, Mantero, F, Spada, A, Falorni, A, Delvecchio, M, De Marinis, L, Martino, E, Rotondi, M, and Chiovato, L.

Subjects
Adult, Male, Human Growth Hormone, Hypothalamus, Autoimmunity, antipituitary and antihypothalamus antibodies, Hypopituitarism, Adrenocorticotropic Hormone, selective idiopathic hypopituitarism, Pituitary Gland, pituitary and hypothalamic autoimmunity, Humans, Female, Fluorescent Antibody Technique, Indirect, Autoantibodies, Hypophysectomy
Abstract

OBJECTIVE: Antipituitary (APA) but not antihypothalamus antibodies (AHA) have been investigated in patients with idiopathic hypopituitarism. This study searched for APA and AHA in some of these patients to investigate whether pituitary or hypothalamic autoimmunity could play a role in their pituitary dysfunction. DESIGN: Sixty-six patients with selective idiopathic hypopituitarism were studied: 27 with ACTH deficiency, 20 with GH deficiency and 19 with hypogonadotropic hypogonadism. Twenty patients with hypopituitarism secondary to hypophysectomy and 50 healthy subjects were enrolled as controls. MEASUREMENTS: Antipituitary and AHA were evaluated by indirect immunofluorescence in sera of patients and controls. Positive sera were retested by a four-layer double immunofluorescence to identify the cells targeted by these antibodies. RESULTS: Antipituitary were present at high titre in 4 of 27 patients with ACTH deficiency (14·8%), 4 of 20 with GH deficiency (26%) and 5 of 19 with hypogonadotropic hypogonadism (21%) and targeted, respectively, corticotrophs, somatotrophs and gonadotrophs. AHA were found at high titre only in 5 patients with ACTH deficiency (18·5%), mostly targeting corticotrophin-releasing hormone-secreting cells; none of these 5 patients resulted positive for antipituitary antibodies. Among the controls, only 1 hypophysectomized patient resulted APA positive at low titre. CONCLUSIONS: Our results suggest that in patients with selective idiopathic hypopituitarism, detection of APA or AHA could better characterize an autoimmune process involving the pituitary or hypothalamus, respectively. In particular, detection of antibodies targeting selectively ACTH-secreting or corticotrophin-releasing hormone-secreting cells may differentiate, respectively secondary from tertiary variants of autoimmune hypoadrenalism

Published
2011

10. Detection of antipituitary and antihypothalamus antibodies to investigate the role of pituitary or hypothalamic autoimmunity in patients with selective idiopathic hypopituitarism

Author

DE BELLIS, ANNAMARIA, DI SOMMA, CAROLINA, COLAO, ANNAMARIA, BELLASTELLA, ANTONIO, Pane E, Bellastella G, Sinisi AA, Colella C, Giordano R, Giavoli C, Lania A, Ambrosio MR, Zatelli MC, Arvat E, Bizzarro A, Italian Autoimmune Hypophysitis Network S.t.u.d.y., DE BELLIS, Annamaria, Pane, E, Bellastella, G, Sinisi, Aa, Colella, C, Giordano, R, Giavoli, C, Lania, A, Ambrosio, Mr, DI SOMMA, Carolina, Zatelli, Mc, Arvat, E, Colao, Annamaria, Bizzarro, A, Bellastella, Antonio, and Italian Autoimmune Hypophysitis Network, S. t. u. d. y.

Subjects
antipituitary and antihypothalamus antibodie, selective idiopathic hypopituitarism
Abstract

OBJECTIVE: Antipituitary (APA) but not antihypothalamus antibodies (AHA) have been investigated in patients with idiopathic hypopituitarism. This study searched for APA and AHA in some of these patients to investigate whether pituitary or hypothalamic autoimmunity could play a role in their pituitary dysfunction. DESIGN: Sixty-six patients with selective idiopathic hypopituitarism were studied: 27 with ACTH deficiency, 20 with GH deficiency and 19 with hypogonadotropic hypogonadism. Twenty patients with hypopituitarism secondary to hypophysectomy and 50 healthy subjects were enrolled as controls. MEASUREMENTS: Antipituitary and AHA were evaluated by indirect immunofluorescence in sera of patients and controls. Positive sera were retested by a four-layer double immunofluorescence to identify the cells targeted by these antibodies. RESULTS: Antipituitary were present at high titre in 4 of 27 patients with ACTH deficiency (14·8%), 4 of 20 with GH deficiency (26%) and 5 of 19 with hypogonadotropic hypogonadism (21%) and targeted, respectively, corticotrophs, somatotrophs and gonadotrophs. AHA were found at high titre only in 5 patients with ACTH deficiency (18·5%), mostly targeting corticotrophin-releasing hormone-secreting cells; none of these 5 patients resulted positive for antipituitary antibodies. Among the controls, only 1 hypophysectomized patient resulted APA positive at low titre. CONCLUSIONS: Our results suggest that in patients with selective idiopathic hypopituitarism, detection of APA or AHA could better characterize an autoimmune process involving the pituitary or hypothalamus, respectively. In particular, detection of antibodies targeting selectively ACTH-secreting or corticotrophin-releasing hormone-secreting cells may differentiate, respectively secondary from tertiary variants of autoimmune hypoadrenalism.

Published
2011

11. Predictive role of the immunostaining pattern of immunofluorescence and the titers of antipituitary antibodies at presentation for the occurrence of autoimmune hypopituitarism in patients with autoimmune polyendocrine syndromes over a five-year follow-up

Author

Bellastella, G, Rotondi, M, Pane, E, Dello Iacovo, A, Pirali, B, Dalla Mora, L, Falorni, A, Sinisi, Aa, Bizzarro, A, Colao, A, Chiovato, L, De Bellis, A, Italian Autoimmune Hypophysitis Network Study, Ambrosio, Mr, Arvat, E, Beck Peccoz, P, Betterle, C, Cannavo', Salvatore, Degli Uberti, E, Giordano, R, Ghigo, E, Lombardi, G, Maghnie, M, Mantero, F, Persani, L, Spada, A, Santeusanio, F, Delvecchio, M., Bellastella, G., Rotondi, M., Pane, E., Dello Iacovo, A., Pirali, B., Dalla Mora, L., Falorni, A., Sinisi, ANTONIO AGOSTINO, Bizzarro, Antonio, Colao, Annamaria, Chiovato, L., DE BELLIS, Annamaria, Italian AutoimmuneHypophysitis Network, S. t. u. d. y., Bellastella, G, Rotondi, M, Pane, E, DELLO IACOVO, A, Pirali, B, DALLA MORA, L, Falorni, A, Sinisi, Aa, Bizzarro, A, Colao, A, Chiovato, L, DE BELLIS, A, Ambrosio, Mr, Arvat, E, BECK-PECOZ, P, Betterle, C, Cannavò, S, DEGLI UBERTI, E, Giordano, R, Ghigo, E, Lombardi, G, Maghnie, M, Mantero, F, Persani, L, Spada, A, Santeusanio, F, and DEL VECCHIO, M.

Subjects
Adult, Male, medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, education, Clinical Biochemistry, Fluorescent Antibody Technique, Context (language use), Hypopituitarism, Immunofluorescence, medicine.disease_cause, Biochemistry, Statistics, Nonparametric, antipituitary antibodie, NO, Autoimmunity, Endocrinology, Anterior pituitary, autoimmune hypopituitarism, Pituitary Gland, Anterior, Predictive Value of Tests, Internal medicine, mental disorders, medicine, Humans, Polyendocrinopathies, Autoimmune, Autoantibodies, medicine.diagnostic_test, biology, business.industry, polyendocrine syndrome, Biochemistry (medical), medicine.disease, antipituitary antibodies, autoimmune polyendocrine syndromes, medicine.anatomical_structure, hypopituitarism, Autoimmune polyendocrine syndrome, immunofluorescence, antipituitary antibodies, poly-endocrine syndrome, biology.protein, Regression Analysis, Female, Antibody, business, Immunostaining, psychological phenomena and processes
Abstract

CONTEXT: Antipituitary antibodies (APA) are frequently present in patients with autoimmune polyendocrine syndrome (APS). DESIGN: The aim was to evaluate the predictive value of APA for the occurrence of hypopituitarism. A total of 149 APA-positive and 50 APA-negative patients with APS and normal pituitary function were longitudinally studied for 5 yr. METHODS: APA, by indirect immunofluorescence, and anterior pituitary function were assessed yearly in all patients. The risk for developing autoimmune pituitary dysfunction was calculated using survival and multivariate analysis. RESULTS: Hypopituitarism occurred in 28 of 149 (18.8%) APA-positive patients but in none of the 50 APA-negative patients. The immunostaining pattern in APA-positive patients involved either isolated pituitary cells [type 1 pattern; n=99 (66.4%)] or all pituitary cells [type 2 pattern; n=50 (33.6%)]. All patients developing pituitary dysfunction throughout the study span had a type 1 pattern. Kaplan-Meier curves for cumulative survival showed a significantly higher rate for developing hypopituitarism in relation to positive APA tests (P

Published
2010

12. ItalianPheochromocytoma/Paraganglioma Network. Clinically guided genetic screening in a large cohort of italian patients with pheochromocytomas and/or functional ornonfunctional paragangliomas

Author

Mannelli M, Castellano M, Schiavi F, Filetti S, Giacchè M, Mori L, Pignataro V, Bernini G, Giachè V, Bacca A, BIONDI, BERNADETTE, Corona G, Di Trapani G, Grossrubatscher E, Reimondo G, Arnaldi G, Giacchetti G, Veglio F, Loli P, COLAO, ANNAMARIA, Ambrosio MR, Terzolo M, Letizia C, Ercolino T, Opocher G., Mannelli, M, Castellano, M, Schiavi, F, Filetti, S, Giacchè, M, Mori, L, Pignataro, V, Bernini, G, Giachè, V, Bacca, A, Biondi, Bernadette, Corona, G, Di Trapani, G, Grossrubatscher, E, Reimondo, G, Arnaldi, G, Giacchetti, G, Veglio, F, Loli, P, Colao, Annamaria, Ambrosio, Mr, Terzolo, M, Letizia, C, Ercolino, T, and Opocher, G.

Subjects
Genetic screening and italian patients with pheochromocytomas
Abstract

The aim of the study was to define the frequency of hereditary forms and the genotype/phenotype correlations in a large cohort of Italian patients with pheochromocytomas and/or functional or nonfunctional paragangliomas.Germline mutations were detected in 32.1% of cases, but frequencies varied widely depending on the classification criteria and ranged from 100% in patients with associated syndromic lesions to 11.6% in patients with a single tumor and a negative family history. The types and number of pheochromocytomas/paragangliomas as well as age at presentation and malignancy suggest which gene should be screened first. Genomic rearrangements were found in two of 160 patients (1.2%).

Published
2009

13. Diagnosis of Burkitt lymphoma using an algorithmic approach--applicable in both resource-poor and resource-rich countries

Author

Naresh, Kn, Ibrahim, Ha, Lazzi, S, Rince, P, Onorati, M, Ambrosio, Mr, BILHOU-NABERA, C, Amen, F, Reid, A, Mawanda, M, Calbi, V, Ogwang, M, Rogena, E, Byakika, B, Sayed, S, Moshi, E, Mwakigonja, A, Raphael, M, Magrath, I, and Leoncini, L.

Subjects
Adult, Diagnosis, Differential, Gene Expression Profiling, Health Resources, Humans, Lymphoma, Large B-Cell, Diffuse, Child, Burkitt Lymphoma, Algorithms, In Situ Hybridization, Fluorescence, Decision Support Techniques, Immunophenotyping
Abstract

Distinguishing Burkitt lymphoma (BL) from B cell lymphoma, unclassifiable with features intermediate between diffuse large B-cell lymphoma (DLBCL) and BL (DLBCL/BL), and DLBCL is challenging. We propose an immunohistochemistry and fluorescent in situ hybridization (FISH) based scoring system that is employed in three phases - Phase 1 (morphology with CD10 and BCL2 immunostains), Phase 2 (CD38, CD44 and Ki-67 immunostains) and Phase 3 (FISH on paraffin sections for MYC, BCL2, BCL6 and immunoglobulin family genes). The system was evaluated on 252 aggressive B-cell lymphomas from Europe and from sub-Saharan Africa. Using the algorithm, we determined a specific diagnosis of BL or not-BL in 82%, 92% and 95% cases at Phases 1, 2 and 3, respectively. In 3·4% cases, the algorithm was not completely applicable due to technical reasons. Overall, this approach led to a specific diagnosis of BL in 122 cases and to a specific diagnosis of either DLBCL or DLBCL/BL in 94% of cases that were not diagnosed as BL. We also evaluated the scoring system on 27 cases of BL confirmed on gene expression/microRNA expression profiling. Phase 1 of our scoring system led to a diagnosis of BL in 100% of these cases.

Published
2011

18. Hypopituitarism and growth hormone deficinecy

Author

Aimaretti, G, Ambrosio, Mr, Benvenga, Salvatore, Borretta, G, DE MARINIS, L, DE MENIS, E, DI SOMMA, C, FAUSTINI FUSTINI, M, Grottoli, S, Gasco, V, Gasperi, M, Logoluso, F, Scaroni, C, Giordano, G, and Ghigo, E.

Published
2004

21. GH/IGF-I axis in aging: multicenter study in 152 healthy elderly subjects with different degrees of physical activity: Italian association for research on brain aging (AIRIC) multicenter study group

Author

Ambrosio, Mr, DEGLI UBERTI, E, Arvat, E, Camanni, F, Ghigo, E, Gianotti, L, Baumann, G, Ceda, Gp, Valenti, G, Cella, Sg, Muller, Ee, Rigamonti, A, Cifani, S, Torri, V, Corradini, C, Fonzi, S, Giordano, F, Minuto, F, Murialdo, G, Polleri, A, Gasperi, Maurizio, Macchia, E, Martino, E, Pinchera, A, Ghidinelli, S, Maestri, P, Pullano, V, Riondino, G, Strollo, F, and Rizzi, G.

Published
1997

23. Effect of δ-opioid receptor agonist deltorphin on circulating concentrations of luteinizing hormone and follicle stimulating hormone in healthy fertile women

Author

Bondanelli, M, Ambrosio, MR, Franceschetti, P, Guerrini, R, Valentini, A, and Ciro degli Uberti, E

Abstract

There is evidence that endogenous opioid peptides exert an inhibitory effect on pituitary luteinizing hormone (LH) secretion both in animals and in humans, by interacting with μ-opioid receptors. However, a role for δ-opioid receptors in the regulation of gonadotrophin releasing hormone (GnRH) secretion has recently been suggested. In the present study, we evaluated the effect of the highly selective δ-opioid receptor agonist deltorphin on the LH and follicle stimulating hormone (FSH) responses to naloxone in six healthy fertile women during the luteal phase of the menstrual cycle. Deltorphin infusion alone (7 μg/kg/min for 60 min) did not significantly change the basal serum concentrations of LH in this group of women. The intravenous (i.v.) bolus administration of naloxone (15 mg) induced a significant (P < 0.001) increase in serum LH concentrations (from a mean basal value of 4.24 ± 1.10 IU/l to a peak of 13.27 ± 1.8 IU/l). The LH response to naloxone was significantly (P < 0.001) blunted by preinfusion of deltorphin (13.27 ± 1.80 IU/l versus 4.80 ± 1.18 IU/l). No significant changes in FSH concentrations were observed during deltorphin, naloxone or deltorphin plus naloxone administration. These data indicate that activation of δ-opioid receptors can reduce naloxone-reduced LH release, suggesting a possible role of δ receptors in opioidergic modulation of LH secretion in women.Keywords: δ-opioid receptors/deltorphin/gonadotrophin/women

Published
1998

24. Growth hormone receptor blockade inhibits growth hormone-induced chemoresistance by restoring cytotoxic-induced apoptosis in breast cancer cells independently of estrogen receptor expression.

Author

Minoia M, Gentilin E, Molè D, Rossi M, Filieri C, Tagliati F, Baroni A, Ambrosio MR, degli Uberti E, Zatelli MC, Minoia, Mariella, Gentilin, Erica, Molè, Daniela, Rossi, Martina, Filieri, Carlo, Tagliati, Federico, Baroni, Alessandra, Ambrosio, Maria Rosaria, degli Uberti, Ettore, and Zatelli, Maria Chiara

Published
2012
Full Text
View/download PDF

25. Real-World Study of Everolimus in Advanced Progressive Neuroendocrine Tumors

Author

Francesca Lugli, Maria Chiara Zatelli, G. Delle Fave, Marialuisa Appetecchia, A. Zaniboni, Alfredo Berruti, Maria Pia Brizzi, Davide Pastorelli, Gabriele Luppi, Giacomo Cartenì, Antongiulio Faggiano, Marco Merlano, Elisabetta Nobili, Carmen Nuzzo, Silvana Chiara, Francesca Spada, C. Funaioli, Francesco Panzuto, Nicola Fazio, Annalisa Fontana, A. Colao, Maria Rosaria Ambrosio, Ferdinando Riccardi, Lorenzo Antonuzzo, Davide Campana, Alfredo Cassano, F. de Braud, Stefano Cascinu, Maria Rinzivillo, Sara Pusceddu, Massimo Falconi, Paola Tomassetti, Panzuto F, Rinzivillo M, Fazio N, de Braud F, Luppi G, Zatelli MC, Lugli F, Tomassetti P, Riccardi F, Nuzzo C, Brizzi MP, Faggiano A, Zaniboni A, Nobili E, Pastorelli D, Cascinu S, Merlano M, Chiara S, Antonuzzo L, Funaioli C, Spada F, Pusceddu S, Fontana A, Ambrosio MR, Cassano A, Campana D, Cartenì G, Appetecchia M, Berruti A, Colao A, Falconi M, Delle Fave G, Panzuto, F, Rinzivillo, M, Fazio, N, de Braud, F, Luppi, G, Zatelli, Mc, Lugli, F, Tomassetti, P, Riccardi, F, Nuzzo, C, Brizzi, M1, Faggiano, Antongiulio, Zaniboni, A, Nobili, E, Pastorelli, D, Cascinu, S, Merlano, M, Chiara, S, Antonuzzo, L, Funaioli, C, Spada, F, Pusceddu, S, Fontana, A, Ambrosio, Mr, Cassano, A, Campana, D, Cartenì, G, Appetecchia, M, Berruti, A, Colao, Annamaria, Falconi, M, and Delle Fave, G.

Subjects
Compassionate Use Trials, Male, Oncology, carcinoid, Cancer Research, medicine.medical_specialty, Drug-Related Side Effects and Adverse Reactions, medicine.medical_treatment, Carcinoid Tumor, Neuroendocrine tumors, Pharmacology, Octreotide, Gastroenterology, Disease-Free Survival, Neuroendocrine, Pancreatic tumors, Everolimus, Internal medicine, Gastrointestinal Cancer, medicine, Humans, Adverse effect, Aged, Neoplasm Staging, Sirolimus, Chemotherapy, business.industry, everolimu, Middle Aged, medicine.disease, NEUROENDOCRINE TUMOURS, Discontinuation, Pancreatic Neoplasms, Neuroendocrine Tumors, Tolerability, Radionuclide therapy, Female, Erratum, business, PANCREATIC ENDOCRINE TUMOR, medicine.drug
Abstract

Everolimus is a valid therapeutic option for neuroendocrine tumors (NETs); however, data in a real-world setting outside regulatory trials are sparse. The aim of this study was to determine everolimus tolerability and efficacy, in relation to previous treatments, in a compassionate use program. A total of 169 patients with advanced progressive NETs treated with everolimus were enrolled, including 85 with pancreatic NETs (pNETs) and 84 with nonpancreatic NETs (non-pNETs). Previous treatments included somatostatin analogs (92.9%), peptide receptor radionuclide therapy (PRRT; 50.3%), chemotherapy (49.7%), and PRRT and chemotherapy (22.8%). Overall, 85.2% of patients experienced adverse events (AEs), which were severe (grade 3–4) in 46.1%. The most frequent severe AEs were pneumonitis (8.3%), thrombocytopenia (7.7%), anemia (5.3%), and renal failure (3.5%). In patients previously treated with PRRT and chemotherapy, a 12-fold increased risk for severe toxicity was observed, with grade 3–4 AEs reported in 86.8% (vs. 34.3% in other patients). In addition, 63.3% of patients required temporarily everolimus discontinuation due to toxicity. Overall, 27.8% of patients died during a median follow-up of 12 months. Median progression-free survival (PFS) and overall survival (OS) were 12 months and 32 months, respectively. Similar disease control rates, PFS, and OS were reported in pNETs and non-pNETs. In the real-world setting, everolimus is safe and effective for the treatment of NETs of different origins. Higher severe toxicity occurred in patients previously treated with systemic chemotherapy and PRRT. This finding prompts caution when using this drug in pretreated patients and raises the issue of planning for everolimus before PRRT and chemotherapy in the therapeutic algorithm for advanced NETs.

Published
2014

26. The alteration of lipid metabolism in burkitt lymphoma identifies a novel marker: adipophilin

Author

Monica Onorati, Stefano Pileri, Claudio Doglioni, Maria Raffaella Ambrosio, Pier Paolo Piccaluga, Martin D. Ogwang, Maurilio Ponzoni, Valeria Malagnino, Kikkeri N. Naresh, Valeria Calbi, Giulia De Falco, Lorenzo Leoncini, Stefano Lazzi, Bruno Jim Rocca, Ambrosio MR, Piccaluga PP, Ponzoni M, Rocca BJ, Malagnino V, Onorati M, De Falco G, Calbi V, Ogwang M, Naresh KN, Pileri SA, Doglioni C, Leoncini L, Lazzi S, Ambrosio, Mr, Piccaluga, Pp, Ponzoni, Maurilio, Rocca, Bj, Malagnino, V, Onorati, M, De Falco, G, Calbi, V, Ogwang, M, Naresh, Kn, Pileri, Sa, Doglioni, Claudio, Leoncini, L, and Lazzi, S.

Subjects
Genetics and Molecular Biology (all), Pathology, Anatomy and Physiology, Lymphoma, lcsh:Medicine, Biochemistry, immune system diseases, Immune Physiology, hemic and lymphatic diseases, Lipid droplet, lcsh:Science, Hematopathology, Multidisciplinary, Tumor, medicine.diagnostic_test, Medicine (all), Burkitt Lymphoma, Diffuse, BCL10, Gene Expression Regulation, Neoplastic, Oncology, Medicine, Oncology Agents, lipids (amino acids, peptides, and proteins), Lymphoma, Large B-Cell, Diffuse, Molecular Pathology, Research Article, medicine.medical_specialty, Clinical Pathology, Perilipin 2, Histopathology, Biology, Biomarkers, Tumor, Humans, Membrane Proteins, Perilipin-2, Staining and Labeling, Lipid Metabolism, Biochemistry, Genetics and Molecular Biology (all), Agricultural and Biological Sciences (all), Molecular Genetics, Diagnostic Medicine, Biopsy, medicine, Large B-Cell, Neoplastic, lcsh:R, Lipid metabolism, medicine.disease, Gene Expression Regulation, Anatomical Pathology, Cytoplasm, Surgical Pathology, biology.protein, lcsh:Q, Burkitt's lymphoma, Biomarkers, General Pathology
Abstract

BACKGROUND: Recent evidence suggests that lipid pathway is altered in many human tumours. In Burkitt lymphoma this is reflected by the presence of lipid droplets which are visible in the cytoplasm of neoplastic cells in cytological preparations. These vacuoles are not identifiable in biopsy section as lipids are "lost" during tissue processing. METHODS AND RESULTS: In this study we investigated the expression of genes involved in lipid metabolism, at both RNA and protein level in Burkitt lymphoma and in other B-cell aggressive lymphoma cases. Gene expression profile indicated a significant over-expression of the adipophilin gene and marked up-regulation of other genes involved in lipid metabolism in Burkitt lymphoma. These findings were confirmed by immunohistochemistry on a series od additional histological samples: 45 out of 47 BL cases showed strong adipophilin expression, while only 3 cases of the 33 of the not-Burkitt lymphoma category showed weak adipophilin expression (p

Published
2012

27. Platelet‐Rich Plasma Increases Growth and Motility of Adipose Tissue‐Derived Mesenchymal Stem Cells and Controls Adipocyte Secretory Function

Author

Federica Passaretti, Vittoria D'Esposito, Maria Rosaria Ambrosio, Claudia Miele, Cecilia Nigro, Gregory Alexander Raciti, Pietro Formisano, Giuseppe Perruolo, Francesco Beguinot, Gilberto Sammartino, Francesco Oriente, Rossella Valentino, D'Esposito, V, Passaretti, F, Perruolo, G, Ambrosio, Mr, Valentino, R, Oriente, F, Raciti, Ga, Nigro, C, Miele, C, Sammartino, G, Beguinot, F, and Formisano, P

Subjects
medicine.medical_specialty, Cell Survival, Adipose tissue, Motility, Biology, Biochemistry, Article, chemistry.chemical_compound, TISSUE REGENERATION, Adipocyte, Internal medicine, Adipocytes, medicine, GROWTH FACTORS, Humans, Regeneration, Platelet, Molecular Biology, Cell Proliferation, Platelet-Rich Plasma, Interleukins, CYTOKINES, Cell Cycle, Mesenchymal stem cell, Gene Expression Regulation, Developmental, Cell Differentiation, Mesenchymal Stem Cells, Cell migration, Articles, Cell Biology, PPAR gamma, Vascular endothelial growth factor, ADIPOSE TISSUE, Endocrinology, chemistry, Platelet-rich plasma
Abstract

Adipose tissue‐derived mesenchymal stem cells (Ad‐MSC) and platelet derivatives have been used alone or in combination to achieve regeneration of injured tissues. We have tested the effect of platelet‐rich plasma (PRP) on Ad‐MSC and adipocyte function. PRP increased Ad‐MSC viability, proliferation rate and G1‐S cell cycle progression, by at least 7‐, 2‐, and 2.2‐fold, respectively, and reduced caspase 3 cleavage. Higher PRP concentrations or PRPs derived from individuals with higher platelet counts were more effective in increasing Ad‐MSC growth. PRP also accelerated cell migration by at least 1.5‐fold. However, PRP did not significantly affect mature adipocyte viability, differentiation and expression levels of PPAR‐γ and AP‐2 mRNAs, while it increased leptin production by 3.5‐fold. Interestingly, PRP treatment of mature adipocytes also enhanced the release of Interleukin (IL)‐6, IL‐8, IL‐10, Interferon‐γ, and Vascular Endothelial Growth Factor. Thus, data are consistent with a stimulatory effect of platelet derivatives on Ad‐MSC growth and motility. Moreover, PRP did not reduce mature adipocyte survival and increased the release of pro‐angiogenic factors, which may facilitate tissue regeneration processes. © 2015 The Authors. Journal of Cellular Biochemistry Published by Wiley Periodicals, Inc. J. Cell. Biochem. 116: 2408–2418, 2015. © 2015 The Authors. Journal of Cellular Biochemistry Published by Wiley Periodicals, Inc.

Published
2015

28. Plasmablastic transformation of a pre-existing plasmacytoma: a possible role for reactivation of Epstein Barr virus infection

Author

Stefano Lazzi, Sara Gazaneo, Giulia De Falco, Lorenzo Leoncini, Veronica Candi, Pier Paolo Piccaluga, Alessandro Gozzetti, Vasileios Mourmouras, Maria Grazia Cusi, Bruno Jim Rocca, Teresa Amato, Maria Raffaella Ambrosio, Lucia Mundo, Ambrosio MR, De Falco G, Gozzetti A, Rocca BJ, Amato T, Mourmouras V, Gazaneo S, Mundo L, Candi V, PICCALUGA P., Cusi MG, Leoncini L, and Lazzi S.

Subjects
Neuroblastoma RAS viral oncogene homolog, Chromosome 7 (human), Epstein-Barr virus,miRNA dysregulation, MYC expression, Plasmablastic lymphoma, Plasmacytoma, Juvenile myelomonocytic leukemia, miRNA dysregulation, Hematopoietic stem cell, Hematology, Biology, medicine.disease, EBV, EBER, MYC expression, Gene expression profiling, Transplantation, Haematopoiesis, medicine.anatomical_structure, hemic and lymphatic diseases, Immunology, microRNA, medicine, Cancer research, Epstein-Barr virus, Plasmablastic lymphoma, Online Only Articles, Plasmacytoma
Abstract

Background: Juvenile myelomonocytic leukemia (JMML) is an aggressive clonal myeloid neoplasm of early childhood associated with mutations in Ras pathway genes (PTPN11, KRAS, NRAS, CBL and NF1). Elevated fetal hemoglobin (HbF) levels and monosomy 7 are frequently observed. Stem cell transplantation is the only available curative treatment option but only provides an event-free survival of about 50%. Aims: Gain insight in the molecular networks involved in JMML pathogenesis based on mRNA, microRNA and long non-coding RNA transcriptome analysis of JMML samples. Methods: Expression of 27958 mRNA probes and 23042 lncRNA probes was assessed in diagnostic bone marrow or peripheral blood mononuclear cells of 63 JMML patients and 5 healthy donors, using a custom designed Agilent array. In addition, cDNA of 768 microRNAs was pre-amplified and quantified using miRNA specific Taqman probes. Results: Unsupervised clustering of an initial cohort of 14 patients generated two subgroups with let-7e and RNA-binding protein LIN28B amongst the most significantly differentially expressed genes. In the final cohort, relative higher LIN28B expression was observed in 35 of 63 cases (55.6%) and was defined as the average of the healthy donors plus three standard deviations. Univariable Cox regression showed that logarithmic LIN28B expression as a dichotomous variable can predict overall survival (p=0.035, exp(B) = 4.227, CI(95%) = 1.108 – 16.125). Patients with higher LIN28B mRNA levels experience a significant worse overall survival (Kaplan-Meier plot, p=0.022). HbF and platelet count were also significant prognostic factors, as described previously (p=0.023 and 0.027 respectively). There was no association between LIN28B expression and Ras pathway mutation status. We observed the strongest miRNA anti-correlation between LIN28B and five let-7 family members (d, b, g, e and a), and the second highest positive mRNA correlation between LIN28B and HMGA2. Recently, it was shown that the LIN28B – let-7 – HMGA2 axis determines higher self-renewal of fetal hematopoietic stem cells (Copley, 2013). This indicates that LIN28B confers augmented self- renewal to leukemic hematopoietic stem cells in JMML and – since this is an early childhood disease – this is potentially already initiated during embryogenesis. JMML patients frequently show elevated HbF levels at diagnosis. A positive correlation was found between LIN28B expression and HbF levels (rs=0.64, p

Published
2014

29. Tumor infiltration by T lymphocytes correlates with the outcome of prostate cancer patients treated with salvage radiotherapy

Author

P. Correale, Tommaso Carfagno, Michele Caraglia, M. Del Vecchio, Luigi Pirtoli, Cirino Botta, Maria Raffaella Ambrosio, Valerio Nardone, Paolo Tini, Pierosandro Tagliaferri, Nardone, V, Botta, C, Ambrosio, Mr, Carfagno, T, Tini, P, Del Vecchio, Mt, Caraglia, M, Tagliaferri, P, Pirtoli, L, and Correale, P

Subjects
0301 basic medicine, Oncology, medicine.medical_specialty, business.industry, medicine.medical_treatment, Hematology, T lymphocyte, medicine.disease, Radiation therapy, 03 medical and health sciences, Prostate cancer, 030104 developmental biology, 0302 clinical medicine, 030220 oncology & carcinogenesis, Internal medicine, Salvage radiotherapy, medicine, business, Infiltration (medical)
Published
2016

30. Alginate-hyaluronan composite hydrogels accelerate wound healing process

Author

Roberto Russo, Maria Rosaria Ambrosio, Pietro Formisano, Vittoria D'Esposito, Ovidio Catanzano, Antonio Calignano, Francesca Ungaro, Carmen Avagliano, Stefano Acierno, C. De Caro, Pietro Russo, Agnese Miro, Fabiana Quaglia, Catanzano, O, D'Esposito, V, Acierno, S, Ambrosio, Mr, De Caro, C, Avagliano, C, Russo, P, Russo, Roberto, Miro, Agnese, Ungaro, Francesca, Calignano, Antonio, Formisano, Pietro, and Quaglia, Fabiana

Subjects
Male, Polymers and Plastics, Alginates, Cell Survival, Cell Line, chemistry.chemical_compound, Glucuronic Acid, In vivo, Cell Movement, Hyaluronic acid, Materials Chemistry, medicine, Animals, Humans, Viability assay, Hyaluronic Acid, Rats, Wistar, Hyaluronan, Wound Healing, integumentary system, Chemistry, Hexuronic Acids, Organic Chemistry, Alginate, Hydrogels, Mesenchymal Stem Cells, Glucuronic acid, HaCaT, Disease Models, Animal, medicine.anatomical_structure, Cross-Linking Reagents, Wound dressing, Self-healing hydrogels, Biophysics, Keratinocyte, Wound healing, Rheology, Internal gelation
Abstract

In this paper we propose polysaccharide hydrogels combining alginate (ALG) and hyaluronan (HA) as biofunctional platform for dermal wound repair. Hydrogels produced by internal gelation were homogeneous and easy to handle. Rheological evaluation of gelation kinetics of ALG/HA mixtures at different ratios allowed understanding the HA effect on ALG cross-linking process. Disk-shaped hydrogels, at different ALG/HA ratio, were characterized for morphology, homogeneity and mechanical properties. Results suggest that, although the presence of HA does significantly slow down gelation kinetics, the concentration of cross-links reached at the end of gelation is scarcely affected. The in vitro activity of ALG/HA dressings was tested on adipose derived multipotent adult stem cells (Ad-MSC) and an immortalized keratinocyte cell line (HaCaT). Hydrogels did not interfere with cell viability in both cells lines, but significantly promoted gap closure in a scratch assay at early (1 day) and late (5 days) stages as compared to hydrogels made of ALG alone (p < 0.01 and 0.001 for Ad-MSC and HaCaT, respectively). In vivo wound healing studies, conducted on a rat model of excised wound indicated that after 5 days ALG/HA hydrogels significantly promoted wound closure as compared to ALG ones (p < 0.001). Overall results demonstrate that the integration of HA in a physically cross-linked ALG hydrogel can be a versatile strategy to promote wound healing that can be easily translated in a clinical setting.

Published
2015
Full Text
View/download PDF

31. Cardiac and metabolic effects of chronic growth hormone and insulin-like growth factor I excess in young adults with pituitary gigantism

Author

Stefania Bonadonna, Ettore C. degli Uberti, M. Gola, Mauro Doga, Andrea Giustina, Maria Rosaria Ambrosio, Maria Chiara Zatelli, Marta Bondanelli, Alessandro Onofri, Bondanelli, M, Bonadonna, S, Ambrosio, Mr, Doga, M, Gola, M, Onofri, A, Zatelli, Mc, Giustina, Andrea, and DEGLI UBERTI, Ec

Subjects
Adult, Male, medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, Diastole, Blood Pressure, Doppler echocardiography, Biology, Left ventricular hypertrophy, Gigantism, Electrocardiography, Ventricular Dysfunction, Left, Insulin-like growth factor, Endocrinology, Internal medicine, Glucose Intolerance, Acromegaly, medicine, Humans, Insulin-Like Growth Factor I, medicine.diagnostic_test, Human Growth Hormone, medicine.disease, Echocardiography, Doppler, Glucose, Circulatory system, Hypertrophy, Left Ventricular, Endocrine gland
Abstract

Chronic growth hormone (GH)/insulin-like growth factor I (IGF-I) excess is associated with considerable mortality in acromegaly, but no data are available in pituitary gigantism. The aim of the study was to evaluate the long-term effects of early exposure to GH and IGF-I excess on cardiovascular and metabolic parameters in adult patients with pituitary gigantism. Six adult male patients with newly diagnosed gigantism due to GH secreting pituitary adenoma were studied and compared with 6 age- and sex-matched patients with acromegaly and 10 healthy subjects. Morphologic and functional cardiac parameters were evaluated by Doppler echocardiography. Glucose metabolism was assessed by evaluating glucose tolerance and homeostasis model assessment index. Disease duration was significantly longer (P < .05) in patients with gigantism than in patients with acromegaly, whereas GH and IGF-I concentrations were comparable. Left ventricular mass was increased both in patients with gigantism and in patients with acromegaly, as compared with controls. Left ventricular hypertrophy was detected in 2 of 6 of both patients with gigantism and patients with acromegaly, and isolated intraventricular septum thickening in 1 patient with gigantism. Inadequate diastolic filling (ratio between early and late transmitral flow velocity

Published
2005

32. Use of Pegvisomant in acromegaly. An Italian Society of Endocrinology guideline

Author

E. De Menis, L. De Marinis, Andrea Giustina, Silvia Grottoli, P. Beck Peccoz, Rosario Pivonello, F. Bogazzi, Salvatore Cannavò, Maria Rosaria Ambrosio, Giustina, A, Ambrosio, Mr, Beck Peccoz, P, Bogazzi, F, Cannavo', S, De Marinis, L, De Menis, E, Grottoli, S, Pivonello, Rosario, Giustina, Andrea, and Pivonello, R.

Subjects
medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, Pegvisomant, Disease, Growth hormone, Endocrinology, Pituitary adenoma, Internal medicine, Acromegaly, medicine, Humans, Stage (cooking), Position Statement, PEGVISOMANT, acromegaly, somatostatin analogs, growth hormone, IGF-1, business.industry, Task force, Human Growth Hormone, Guideline, Receptors, Somatotropin, medicine.disease, Italy, Somatostatin analogs, Practice Guidelines as Topic, IGF-1, business, medicine.drug
Abstract

Acromegaly management is a significant challenge for endocrinologists. The Acromegaly Consensus Group developed several statements on the management of acromegaly and specifically on its medical treatment [1–3]. Acromegaly is a quite rare condition generally caused by a growth hormone (GH)-secreting pituitary adenoma [4]. Delayed diagnosis leads to prevalent presentation of the disease at the stage of macroadenoma (two-thirds of patients) and frequent persistence of active disease after surgery which remains in many patients the primary treatment option [5]. However, active acromegaly is potentially a life threatening condition due its severe systemic complications [6, 7] Therefore, elevated GH and insulin-like growth factor (IGF)-1 levels need to be strictly controlled after failure of surgery with medical or radiation treatments [8]. Furthermore, criteria for disease control may not be fulfilled in a considerable proportion of patients undergoing medical treatment with somatostatin receptor ligands (SRLs) after unsuccessful surgery [9, 10]. Accordingly, some acromegaly patients require the administration of GH antagonist Pegvisomant [11]. Pegvisomant has been introduced in clinical practice more than a decade ago as a medical therapy of acromegaly. However, specific guidelines for Pegvisomant use in acromegaly are lacking. Therefore, the Italian Society of Endocrinology constituted a task force with the objective of assessing the published literature and the clinical experience with Pegvisomant. This group involved endocrinologists recognized experts in the field of acromegaly management and their understanding of the data reported so far worldwide as well as their recommendations for Pegvisomant use in clinical practice are presented here. Biochemical and clinical results of Pegvisomant, indications, treatment modalities, combination therapies, safety and regulatory and cost/efficacy issues were evaluated. Evidences were graded with GRADE system [1–3, 12, 13] based on the quality of evidence as very low quality (VLQ; expert opinion with one or a small number of small uncontrolled studies in support), low quality (LQ; large series of small uncontrolled studies), moderate quality (MQ; one or a small number of large uncontrolled studies or meta-analyses), or high quality (HQ; controlled studies or large series of large uncontrolled studies with sufficiently long follow-up). Recommendations were defined discretionary (DR) if based on VLQ-LQ evidence, or strong (SR) if supported by MQ-HQ evidence.

Published
2014

33. Benign glomus tumor of the urinary bladder

Author

Vasileios Mourmouras, Maurizio Colecchia, Gabriele Barbanti, Sergio Tripodi, Bruno Jim Rocca, Maria Raffaella Ambrosio, Tripodi, Sa, Rocca, Bj, Mourmouras, V, Barbanti, G, Colecchia, M, and Ambrosio, Mr.

Subjects
Male, Pathology, medicine.medical_specialty, Anterior wall, Pathology and Forensic Medicine, Polypoid Lesion, Bladder Neoplasm, Biopsy, medicine, Humans, Hematuria, Urinary bladder, medicine.diagnostic_test, business.industry, fungi, General Medicine, Cystoscopy, Middle Aged, medicine.disease, Glomus Tumor, Treatment Outcome, Urinary Bladder Neoplasms, 2734, Medical Laboratory Technology, Glomus tumor, Benign Glomus Tumor, medicine.anatomical_structure, business
Abstract

Glomus tumors are rare, mesenchymal neoplasms of adulthood, which occur in both the sexes with equal frequency. Most of these tumors are benign, but some cases with atypical/malignant behavior have been reported. They most often occur in the extremities, typically in the subungual region of the fingers, and rarely involve the internal organs. We report the case of a 63-year-old man who presented with hematuria. The cystoscopy showed a polypoid lesion of the anterior wall of the bladder, which was diagnosed on biopsy as a benign glomus tumor. To the best of our knowledge, this is the first case of benign glomus tumor of the bladder described in the literature. This report widens the spectrum of the differential diagnoses of bladder neoplasms.

Published
2013

34. Assessment of the awareness and management of cardiovascular complications of acromegaly in Italy. The COM.E.T.A. (COMorbidities Evaluation and Treatment in Acromegaly) Study

Author

Giustina, A., Mancini, T., Boscani, P. F., De Menis, E., Degli Uberti, E., Ghigo, E., Martino, E., Minuto, F., Colao, A., Comorbidities Evaluation, Com E. T. A., Treatment Inacromegaly Italian Study Group, Aimaretti, G., Ambrosio, M. R., Andreani, M., Angeletti, G., Appetecchia, M. L., Armigliato, M., Arnaldi, G., Arosio, M., Babini, A., Baldi, F., Balza, G., Barbaro, D., Bartalena, L., Battista, C., Bechi, R., Beck Peccoz, P., Bellastella, A., Bevilacqua, M., Boccuzzi, G., Boffano, G. M., Bondanelli, M., Borretta, G., Boscaro, M., Buschini, M., Campanini, M., Cannavo, S., Carani, C., Carpenito, F., Carzaniga, C., Castelli, A., Cavagnini, F., Chiarini, V., Chiodera, P., Colombo, M., Colombo, P., Coppola, A., Cozzi, R., Crivellaro, C., D'Antonio, R., Davi, M., De Marinis, L., De Matte, S., De Remigis, P., Del Monte, P., Delitala, G., Doveri, G., D'Ulizia, M., Favro, S., Ferone, D., Fidotti, E., Formoso, G., Francia, G., Frigato, F., Furlani, L., Galuzzo, A., Gargiulo, P., Gasperoni, P., Gazzaruso, C., Giorgino, F., Grandi, M., Grimaldi, F., Indovina, S., Lanzi, R., Legovini, P., Limone, P., Liuzzi, A., Lo Cascio, V., Lo Coco, R., Loli, P., Mantero, F., Marchetti, M., Mariotti, S., Masala, A., Meringolo, D., Monachesi, M., Montini, M., Moretti, C., Muggeo, M., Mulas, G., Nizzolo, M., Oleandri, S., Orio, F., Orlandi, F., Pacini, F., Palermo, M., Pancotti, D., Paoletta, A., Papini, E., Parillo, M., Parisi, G., Pasquali, R., Pavoncello, S., Perego, M. R., Peri, A., Peri, D., Piantoni, L., Raffa, M., Raggiunti, B., Resmini, E., Rizzi, G., Rosatello, A., Rosato, F., Savino, L., Scaroni, C., Sinisi, A., Stefani, I., Tamburrano, G., Tanda, M., Terzolo, M., Testa, I., Testa, R., Testori, G., Toscano, Vincenzo, Tota, N., Travaglini, P., Vailati, A., Valcavi, R., Ventre, I., Vincenzi, W., Vitale, G., A., Giustina, T., Mancini, P. F., Boscani, E., de Meni, E., degli Uberti, E., Ghigo, E., Martino, F., Minuto, Colao, Annamaria, Giustina A, Mancini T, Boscani PF, de Menis E, degli Uberti E, Ghigo E, Martino E, Minuto F, Colao A, Aimaretti G, Ambrosio MR, Andreani M, Angeletti G, Appetecchia ML, Armigliato M, Arnaldi G, Arosio M, Babini A, Baldi F, Balza G, Barbaro D, Bartalena L, Battista C, Bechi R, Beck-Peccoz P, Bellastella A, Bevilacqua M, Boccuzzi G, Boffano GM, Bondanelli M, Borretta G, Boscaro M, Buschini M, Campanini M, Cannavò S, Carani C, Carpenito F, Carzaniga C, Castelli A, Cavagnini F, Chiarini V, Chiodera P, Colombo M, Colombo P, Coppola A, Cozzi R, Crivellaro C, D'Antonio R, Davì M, De Marinis L, De Mattè S, De Remigis P, Del Monte P, Delitala G, Doveri G, D'Ulizia M, Favro S, Ferone D, Fidotti E, Formoso G, Francia G, Frigato F, Furlani L, Galuzzo A, Gargiulo P, Gasperoni P, Gazzaruso C, Giorgino F, Grandi M, Grimaldi F, Indovina S, Lanzi R, Legovini P, Limone P, Liuzzi A, Lo Cascio V, Lo Coco R, Loli P, Mantero F, Marchetti M, Mariotti S, Masala A, Meringolo D, Monachesi M, Montini M, Moretti C, Muggeo M, Mulas G, Nizzolo M, Oleandri S, Orio F, Orlandi F, Pacini F, Palermo M, Pancotti D, Paoletta A, Papini E, Parillo M, Parisi G, Pasquali R, Pavoncello S, Perego MR, Peri A, Peri D, Piantoni L, Raffa M, Raggiunti B, Resmini E, Rizzi G, Rosatello A, Rosato F, Savino L, Scaroni C, Sinisi A, Stefani I, Tamburrano G, Tanda M, Terzolo M, Testa I, Testa R, Testori G, Toscano V, Tota N, Travaglini P, Vailati A, Valcavi R, Ventre I, Vincenzi W, Vitale G., Giustina, Andrea, Mancini, T, Boscani, Pf, DE MENIS, E, DEGLI UBERTI, E, Ghigo, E, Martino, E, Minuto, F, Colao, A, and Italian Study Group, C. O. M. E. T. A.

Subjects
Questionnaires, cardiovascular risk, medicine.medical_specialty, Pathology, Ambulatory blood pressure, Cardiomyopathy, Endocrinology, Diabetes and Metabolism, MEDLINE, Disease, heart, Comorbidity, Left ventricular hypertrophy, NO, Endocrinology, Patient Education as Topic, Surveys and Questionnaires, Acromegaly, medicine, Humans, Intensive care medicine, Awareness, Echocardiography, Hypertension, Questionnaire, business.industry, Cardiovascular Diseases, Epidemiologic Studies, Follow-Up Studies, medicine.disease, Blood pressure, Heart failure, business
Abstract

Background: During the course of acromegaly, cardiovascular, respiratory, and metabolic co-morbidities contribute to enhanced mortality. In 2002, the Pituitary Society and the European Neuroendocrine Association sponsored a Consensus Workshop in Versailles during which guidelines for diagnosis and treatment of co-morbidities in acromegaly were defined. However, as for other guidelines previously issued in the field, no data are available on their clinical application. Aim: The aim of this work coordinated by the Italian Study group on co-morbidities evaluation and treatment in acromegaly (COM.E.T.A.) was to assess, on a national basis, the application in the clinical practice of the Versailles criteria for diagnosis and treatment of cardiovascular comorbities in acromegaly. Materials and methods: In January 2007 an ad hoc designed questionnaire was sent by mail to 130 endocrine Centers in Italy. Results: The guidelines have been generally well perceived and translated in clinical practice. Specifically: 1) echocardiography is considered the mainstay for the diagnosis and follow-up; 2) ambulatory blood pressure monitoring and blood lipid assessment are performed in most hypertensive patients; 3) most endocrinologists directly manage hypertension and are aware of the uncertainty of the effect of the control of the disease on blood pressure levels; 4) ACE inhibitors and angiotensin receptors blockers are first-choice anti-hypertensive treatment; 5) approximately half of the centers consider somatostatin analogues of paramount relevance for biochemical control of disease; 6) awareness that left ventricular hypertrophy and heart failure are the most relevant cardiovascular complications is high although the impact of ischemic, arrhythmic, and valvular complications on prognosis is less well perceived. Conclusion: The results of the present survey suggest that previuosly issued guidelines are generally carefully followed in the clinical practice. On the other side, a certain lack of awareness of emerging aspects of the cardiovascular comorbities of acromegaly confirms the necessity of periodically updating the guidelines based on the availability of new clinical information.

Published
2008

35. Prognostic significance of the Ki-67 labeling index in growth hormone-secreting pituitary adenomas

Author

Antonio Bianchi, Maria Chiara Zatelli, Andrea Giustina, Alessandra Fusco, L. De Marinis, Valerio Gaetano Vellone, Giulio Maira, Francesco Doglietto, L. Tilaro, F Veltri, Alfredo Pontecorvi, Maria Rosaria Ambrosio, Libero Lauriola, Flavia Angelini, Vincenzo Cimino, E. C. Degli Uberti, Fusco, A, Zatelli, Mc, Bianchi, A, Cimino, V, Tilaro, L, Veltri, F, Angelini, F, Lauriola, L, Vellone, V, Doglietto, F, Ambrosio, Mr, Maira, G, Giustina, Andrea, DEGLI UBERTI, Ec, Pontecorvi, A, and DE MARINIS, L.

Subjects
Adenoma, Adult, Male, Pituitary gland, medicine.medical_specialty, Prognosi, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, Clinical Biochemistry, Context (language use), Biochemistry, Endocrinology, Aged, Female, Growth Hormone-Secreting Pituitary Adenoma, Humans, Immunohistochemistry, Ki-67 Antigen, Middle Aged, Prognosis, Somatostatin, Pituitary adenoma, Internal medicine, medicine, Transsphenoidal surgery, medicine.diagnostic_test, business.industry, Biochemistry (medical), Settore MED/13 - ENDOCRINOLOGIA, Magnetic resonance imaging, medicine.disease, medicine.anatomical_structure, Cavernous sinus, Ki-67, business, Human
Abstract

Ki-67 is a marker of proliferation activity associated with invasiveness and prognosis in human tumors.The aim of the study was to evaluate the Ki-67 index prognostic relevance in a group of acromegalic patients who underwent transsphenoidal surgery for a GH-secreting pituitary adenoma.We selected 68 consecutive acromegalic patients referred to our hospital during a 5-yr period. The Ki-67 index was determined by immunohistochemistry on tissue samples obtained from each adenoma after surgery. Those patients who were not completely cured after surgery began medical therapy with somatostatin analogs (SSAs). Periodical pituitary magnetic resonance imaging and hormonal evaluation were performed during the follow-up.Twenty-eight of 68 patients were cured after surgery (41%). Among the 40 patients treated with SSAs, 13 were considered uncontrolled. Pituitary magnetic resonance imaging showed residual/recurrent disease in 25 of 68 patients after 6 months. No correlation was found between Ki-67 index and age, tumor size, GH, or IGF-I plasma levels. Tumors described as having cavernous sinus invasion had a higher mean Ki-67 index as compared with noninvasive tumors (P0.01). The Ki-67 index was significantly lower in tumors in patients cured after surgery as compared with patients considered not cured (P0.01) and in tumors in patients controlled by SSA therapy as compared with patients considered as uncontrolled (P0.05).The Ki-67 labeling index may predict clinical outcome in postsurgical management of acromegalic patients. We suggest routine Ki-67 evaluation in GH-secreting pituitary adenomas.

Published
2008

36. Efficacy and safety of the new 60-mg formulation of the long-acting somatostatin analog lanreotide in the treatment of acromegaly

Author

Guido Tamburrano, Roberto Baldelli, Andrea Giustina, Marta Bondanelli, Maria Rosaria Ambrosio, Ettore C. degli Uberti, Mauro Doga, Paola Franceschetti, Nicola Sicolo, Pietro Maffei, Ambrosio, Mr, Franceschetti, P, Bondanelli, M, Doga, M, Maffei, P, Baldelli, R, Tamburrano, G, Sicolo, N, Giustina, Andrea, and DEGLI UBERTI, Ec

Subjects
Adult, Male, medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, Lanreotide, Injections, Intramuscular, Peptides, Cyclic, Group B, Drug Administration Schedule, chemistry.chemical_compound, Endocrinology, Internal medicine, Acromegaly, medicine, Humans, Insulin-Like Growth Factor I, Aged, Dose-Response Relationship, Drug, business.industry, Human Growth Hormone, Pituitary tumors, Middle Aged, medicine.disease, Somatostatin, Treatment Outcome, chemistry, Tolerability, Delayed-Action Preparations, Toxicity, Female, Safety, Somatostatin analog, business
Abstract

Recently, a new slow-release (SR) formulation of lanreotide (LAN) comprising 60 mg of the drug incorporated in microspheres of biodegradable polymers (SR-LAN 60) has become available. The aim of our study was to assess the effectiveness of SR-LAN 60, administered every 21 to 28 days, as well as its tolerability in the long-term treatment of acromegalic patients treated with SR-LAN 30. Twenty patients with acromegaly (10 males and 10 females) were enrolled in this open study. Thirteen patients had undergone surgery, but with incomplete resection of the pituitary tumor. All patients, treated with intramuscular (IM) SR-LAN 30 injections every 10 days for 12 to 24 months, started SR-LAN 60 (Ipsen-Beaufour, Milan, Italy) administration 10 days after the last injection of SR-LAN 30. Growth hormone (GH) levels were determined on the day of the first injection of SR-LAN 60, and 10, 20, and 30 days after. According to the GH levels reached on day 30, patients received SR-LAN 60 every 28 days if GH levels were below 2.5 microg/L (group A) and every 21 days if GH levels were above 2.5 microg/L (group B). In group A, after the 8th month, SR-LAN 60 treatment resulted in well-controlled GH levels in 9 of 10 patients in comparison to SR-LAN 30 treatment every 10 days (6 of 10 patients). Normal age-adjusted insulin-like growth factor-I (IGF-I) levels were achieved in 4 of 10 patients, as in treatment with SR-LAN 30. In group B, SR-LAN 60 treatment resulted in well-controlled GH levels in 4 of 10 patients, as in treatment with SR-LAN 30 every 10 days. Normal age-adjusted IGF-I levels were achieved in 3 of 10 patients after SR-LAN 60 in comparison to SR-LAN 30 treatment every 10 days (1 of 10 patients). During SR-LAN 60 therapy, an improvement was also observed in signs and symptoms of active acromegaly and no relevant side effects were detected. In conclusion, this study shows that SR-LAN 60 treatment is able to induce a good control of circulating GH and IGF-I levels in most acromegalic patients. The first injections of SR-LAN 60 are very helpful in predicting the optimal long-term injection frequency. Patients on SR-LAN 30 can be safely and effectively shifted to SR-LAN 60.

Published
2002

37. Blood growth hormone-binding protein levels in premenopausal and postmenopausal women: roles of body weight and estrogen levels

Author

Bondanelli, M., Margutti, A., Ambrosio, M. R., Plaino, D., Cobellis, L., Petraglia, F., DEGLI UBERTI, E. C., Bondanelli, M, Margutti, A, Ambrosio, Mr, Plaino, L, Cobellis, Luigi, Petraglia, F, and DEGLI UBERTI, Ec

Subjects
Adult, Endocrinology, Diabetes and Metabolism, Biochemistry (medical), Clinical Biochemistry, Body Weight, Estrogens, Middle Aged, Biochemistry, Body Mass Index, Postmenopause, Endocrinology, Premenopause, Humans, Female, Insulin-Like Growth Factor I, Carrier Proteins, Aged
Abstract

A substantial proportion of GH circulates bound to high affinity GH-binding protein (GHBP), which corresponds to the extracellular domain of the GH receptor. Current evidence indicates that nutritional status has an important role in regulating plasma GHBP levels in humans. In the present study the relationship among plasma GHBP levels, body composition [by bioelectrical impedance analysis (BIA) and dual energy x-ray absorptiometry (DEXA)] and serum estradiol (E2) was evaluated in premenopausal (n 5 92) and postmenopausal (n 5 118) healthy women with different body weight [three groups according to body mass index (BMI): normal, 18.5–24.99; overweight, 25–29.99; obese, 30–39.99 kg/m2]. Plasma GHBP levels were measured by high pressure liquid chromatography gel filtration. GH and insulin-like growth factor I levels were determined by immunoradiometric assay and RIA, respectively. GHBP levels were significantly higher in premenopausal women with BMI above 25 kg/m2 (overweight, 3.789 6 0.306 nmol/L; obese, 4.37260.431 nmol/L) than those observed in postmenopausal women (overweight, 1.425 6 0.09 nmol/L; obese, 1.506 6 0.177 nmol/L). No significant differences were found between normal weight premenopausal (1.741 6 0.104 nmol/L) and postmenopausal (1.524 6 0.202 nmol/L) women. In premenopausal women GHBP levels correlated positively with BMI (r 5 0.675; P , 0.001), fat mass (FM; r 5 0.782; P , 0.001; by BIA; r 5 0.776; P , 0.001; by DEXA), truncal fat (TF; r 5 0.682; P , 0.001), waist to hip circumference ratio (WHR; r 5 0.551; P , 0.001), and E2 (r 5 0.298; P , 0.05), whereas no significant correlation was found in postmenopausal women between GHBP levels and BMI, FM, TF, WHR, or E2. In normal weight pre- and postmenopausal women GHBP levels did not change between the ages of 20 and 69 yr. No statistically significant correlation was found between GHBP and age for all groups studied. Moreover, in two distinct subgroups of pre- and postmenopausal women, aged 40–49 yr, the direct relationship between GHBP levels and all indexes of adiposity were only observed in premenopausal women [BMI: r 5 0.836; P , 0.001; FM: r 5 0.745 (BIA) and r 5 0.832 (DEXA); P , 0.001; TF: r 5 0.782; P , 0.001; WHR: r 5 0.551; P , 0.05], but not in postmenopausal women. In conclusion, the present data indicate a strong direct correlation between GHBP and body fat in premenopausal, but not in postmenopausal women, whereas they failed to detect a relationship between GHBP and age. Therefore, these results suggest that endogenous estrogen status may be an important determinant of the changes in GHBP levels in women with different body weights.

Published
2001

38. Adipose microenvironment promotes triple negative breast cancer cell invasiveness and dissemination by producing CCL5

Author

Claudia Miele, Gerardo Botti, Pietro Campiglia, Maurizio Di Bonito, Rossella Valentino, Maria Rosaria Ambrosio, Domenico Liguoro, Francesco Beguinot, Rosa Spinelli, Renato Franco, Monica Cantile, Vittoria D'Esposito, Pietro Formisano, Francesca Collina, Gregory Alexander Raciti, Michelino De Laurentiis, D'Esposito, V, Liguoro, D, Ambrosio, Mr, Collina, Anna, Cantile, M, Spinelli, R, Raciti, Ga, Miele, C, Valentino, R, Campiglia, P, De Laurentiis, M, Di Bonito, M, Botti, G, Franco, R, Beguinot, F, Formisano, P, D'Esposito, Vittoria D., Liguoro, Domenico, Ambrosio, Maria Rosaria, Collina, Francesca, Cantile, Monica, Spinelli, Rosa, Raciti, Gregory Alexander, Miele, Claudia, Valentino, Rossella, Campiglia, Pietro, De Laurentiis, Michelino, Bonito, Maurizio Di, Botti, Gerardo, Franco, Renato, Beguinot, Francesco, and Formisano, Pietro

Subjects
0301 basic medicine, Adult, Pathology, medicine.medical_specialty, Breast surgery, medicine.medical_treatment, Adipose tissue, Triple Negative Breast Neoplasms, Kaplan-Meier Estimate, Diabete, CCL5, Metastasis, 03 medical and health sciences, 0302 clinical medicine, Cell Movement, Cell Line, Tumor, medicine, Adipocytes, Humans, Neoplasm Invasiveness, Triple negative breast cancer, Obesity, Lymph node, Chemokine CCL5, Cytokine, Triple-negative breast cancer, Cancer prevention, business.industry, Diabetes, Middle Aged, medicine.disease, Coculture Techniques, Gene Expression Regulation, Neoplastic, 030104 developmental biology, medicine.anatomical_structure, Cellular Microenvironment, Oncology, 030220 oncology & carcinogenesis, Lymphatic Metastasis, Cancer cell, Cancer research, MCF-7 Cells, Cytokines, Female, business, Research Paper
Abstract

// Vittoria D'Esposito 1 , Domenico Liguoro 1 , Maria Rosaria Ambrosio 1 , Francesca Collina 2 , Monica Cantile 2 , Rosa Spinelli 1 , Gregory Alexander Raciti 1 , Claudia Miele 1 , Rossella Valentino 1 , Pietro Campiglia 3 , Michelino De Laurentiis 4 , Maurizio Di Bonito 2 , Gerardo Botti 2 , Renato Franco 2 , Francesco Beguinot 1 , Pietro Formisano 1 1 Department of Translational Medicine, Federico II University of Naples and URT “Genomic of Diabetes” of Institute of Experimental Endocrinology and Oncology, National Council of Research (CNR), Naples, Italy 2 Pathology Unit, National Institute of Tumors, Fondazione “G. Pascale”, Naples, Italy 3 Department of Pharmacy, University of Salerno, Salerno, Italy 4 Department of Breast Surgery and Cancer Prevention; National Institute of Tumors, Fondazione “G. Pascale”, Naples, Italy Correspondence to: Pietro Formisano, e-mail: fpietro@unina.it Keywords: triple negative breast cancer, adipose tissue, cytokines, diabetes, obesity Received: August 05, 2015 Accepted: February 28, 2016 Published: March 24, 2016 ABSTRACT Growing evidence indicates that adiposity is associated with raised cancer incidence, morbidity and mortality. In a subset of tumors, cancer cell growth and/or metastasis predominantly occur in adipocyte-rich microenvironment. Indeed, adipocytes represent the most abundant cell types surrounding breast cancer cells. We have studied the mechanisms by which peritumoral human adipose tissue contributes to Triple Negative Breast Cancer (TNBC) cell invasiveness and dissemination. Co-culture with human adipocytes enhanced MDA-MB231 cancer cell invasiveness. Adipocytes cultured in high glucose were 2-fold more active in promoting cell invasion and motility compared to those cultured in low glucose. This effect is induced, at least in part, by the CC-chemokine ligand 5 (CCL5). Indeed, CCL5 inhibition by specific peptides and antibodies reduced adipocyte-induced breast cancer cell migration and invasion. CCL5 immuno-detection in peritumoral adipose tissue of women with TNBC correlated with lymph node ( p -value = 0.04) and distant metastases ( p -value = 0.001). A positive trend was also observed between CCL5 expression and glycaemia. Finally, Kaplan-Meier curves showed a negative correlation between CCL5 staining in the peritumoral adipose tissue and overall survival of patients ( p -value = 0.039). Thus, inhibition of CCL5 in adipose microenvironment may represent a novel approach for the therapy of highly malignant TNBC.

39. Comparison between two methods in the determination of circulating chromogranin A in neuroendocrine tumors (NETs): Results of a prospective multicenter observational study

Author

G. Delle Fave, Mirella Torta, F. de Braud, Massimo Gion, Antonette E. Leon, Maria Rosaria Ambrosio, E. C. Degli Uberti, Luigi Dogliotti, Ruggero Dittadi, Paola Tomassetti, Leon A., Torta M., Dittadi R., degli Uberti E., Ambrosio MR., Delle Fave G., De Braud F., Tomassetti P., Gion M., and Dogliotti L.

Subjects
0301 basic medicine, Adult, Male, Cancer Research, medicine.medical_specialty, Clinical Biochemistry, Enzyme-Linked Immunosorbent Assay, Neuroendocrine tumors, Gastroenterology, Pathology and Forensic Medicine, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, Biomarkers, Tumor, Chromogranins, Confidence Intervals, Humans, In patient, Prospective Studies, Aged, Immunoradiometric assay, biology, business.industry, Chromogranin A, Reproducibility of Results, Radioimmunoassay, Middle Aged, medicine.disease, Laboratories, Hospital, Neuroendocrine Tumors, 030104 developmental biology, Oncology, Multicenter study, Italy, 030220 oncology & carcinogenesis, Monoclonal, Immunology, biology.protein, Observational study, Female, Immunoradiometric Assay, Reagent Kits, Diagnostic, business
Abstract

Several methods for analyzing CgA using either monoclonal or polyclonal antibodies have been developed, which differ in their diagnostic performance. The present paper describes the results of a prospective multicenter study aimed at comparing the clinical value of the two most widely used commercially available CgA assay kits in patients affected by neuroendocrine tumors (NETs). Two hundred sixty-one patients from 40 different centers and 99 healthy subjects were evaluated. CgA levels were measured with two different methods, a two-step immunoradiometric assay (IRMA) and an enzyme-linked immunosorbent assay (ELISA). CgA was measured centrally by two reference laboratories, one of which used IRMA and the other ELISA, and it was measured by the participating institutions with the method routinely used by each of them. The major findings of the present study were: (i) the two assays for the determination of CgA present good diagnostic performance; (ii) both assays are robust and guarantee comparable results when applied in different settings (central vs local laboratory); (iii) the negative/positive cutoff points (87 ng/mL for IRMA and 21.3 U/L for ELISA) were established according to standardized criteria; (iv) the results obtained with the two assays in basal clinical samples of patients affected by NETs show an apparently satisfactory correlation (rs=0.843, p

40. The alteration of lipid metabolism in Burkitt lymphoma identifies a novel diagnostic marker: the adipophilin

Author

Lazzi, S., Lorenzo LEONCINI, Doglioni, C., Naresh, K. N., Ogwang, M., Onorati, M., Pileri, S. A., Malagnino, V., Rocca, B. J., Calbi, V., Ponzoni, M., Falco, G., Piccaluga, P. P., Maria Raffaella Ambrosio, Ambrosio, Mr, Piccaluga, Pp, Ponzoni, Maurilio, Rocca, Bj, Malagnino, V, Onorati, M, De Falco, G, Calbi, V, Ogwang, M, Naresh, Kn, Pileri, Sa, Doglioni, C, Leoncini, L, and Lazzi, S.

41. Pituitary and COVID-19 vaccination: a systematic review.

Author

Verrienti M, Marino Picciola V, Ambrosio MR, and Zatelli MC

Abstract

Purpose: This systematic review aims to examine the latest research findings and assess the impact of COVID-19 vaccination on the pituitary gland., Method: PubMed and Tripdatabase were searched from January 1st, 2020 to February 12th, 2024. Case reports, case series and reviews related to post COVID-19 vaccination pituitary disease were included. Eligible articles were tabulated and analysed in the attempt to provide an overview on the epidemiology, clinical presentation, imaging, treatment, outcomes and pathophysiological background of post COVID-19 vaccination pituitary disease., Results: Among the 23 case reports included in this review, post COVID-19 vaccination hypophysitis was reported in 9 patients, pituitary apoplexy (PA) in 6 cases, SIADH in 5 cases and Isolated ACTH deficiency in 2 cases. Additionally, precipitating adrenal crisis was registered in 7 patients and pituitary tumor enlargement in 1 patient after receiving COVID-19 vaccination., Conclusion: Despite the rarity of these events, our research findings suggest an association between COVID-19 vaccination and the subsequent development of pituitary diseases. The most common manifestations include hypophysitis with ADH deficiency, PA and SIADH, with symptoms typically emerging shortly after vaccine administration. Potential pathogenetic mechanisms include molecular mimicry, vaccine adjuvants and vaccine-induced thrombotic thrombocytopenia (VITT), with the presence of ACE2 receptors in the hypothalamus-pituitary system contributing to the process. These findings can aid in diagnostic and treatment decisions for patients presenting with these syndromes. Nevertheless, given the rarity of these events, safety and efficacy of the currently available COVID-19 vaccines remain robust and we strongly advocate continuing pursuing vaccination efforts., (© 2024. The Author(s).)

Published
2024
Full Text
View/download PDF

42. Alcohol use disorders and liver fibrosis: an update.

Author

Caputo F, Penitenti F, Bergonzoni B, Lungaro L, Costanzini A, Caio G, DE Giorgio R, Ambrosio MR, Zoli G, and Testino G

Abstract

Alcoholic liver disease (ALD) is currently, worldwide, the second most common cause of human fatalities every year. Alcohol use disorders (AUDs) lead to 80% of hepatotoxic deaths, and about 40% of cases of cirrhosis are alcohol-related. An acceptable daily intake (ADI) of ethanol is hard to establish and studies somewhat controversially recommend a variety of dosages of ADI, whilst others regard any intake as dangerous. Steatohepatitis should be viewed as "the rate limiting step": generally, it can be overcome by abstinence, although in some patients, abstinence has little effect, with the risk of fibrosis, leading in some cases to hepatocellular carcinoma (HCC). Chronic alcoholism can also cause hypercortisolism, specifically pseudo-Cushing Syndrome, whose diagnosis is challenging. If fibrosis is spotted early, patients may be enrolled in detoxification programs to achieve abstinence. Treatment drugs include silybin, metadoxine and adenosyl methionine. Nutrition and the proper use of micronutrients are important, albeit often overlooked in ALD treatment. Other drugs, with promising antifibrotic effects, are now being studied. This review deals with the clinical and pathogenetic aspects of alcohol-related liver fibrosis and suggests possible future strategies to prevent cirrhosis.

Published
2024
Full Text
View/download PDF

43. Late orbital radiotherapy combined with intravenous methylprednisolone in the management of long-lasting active graves' orbitopathy: a case report and literature review.

Author

Verrienti M, Gagliardi I, Valente L, Stefanelli A, Borgatti L, Franco E, Galiè M, Bondanelli M, Zatelli MC, and Ambrosio MR

Abstract

Purpose: To present a case and review the literature on Orbital Radiotherapy (OR) combined with intravenous methylprednisolone, focusing on its late application in patients with long-lasting active Graves' Orbitopathy (GO). Additionally, we suggest emerging perspective for future research in this context., Method: Relevant literature (randomized controlled studies, retrospective studies and reviews) was explored on PubMed from January 1973 to January 2024, searching "orbital radiotherapy" & "Graves disease"., Results: OR is a well-established second-line treatment for moderate-to-severe active GO, providing response rates comparable to glucocorticoids. Its anti-inflammatory effect makes OR particularly suitable for early active GO, and when combined with glucocorticoids, outcomes are synergistically improved. The emergence of the new Volumetric Modulated Arc Image-Guided Radiation Therapy (VMAT-IGRT) technique enables precise radiation delivery to the target, significantly reducing associated toxicity. This technological advancement enhances the feasibility of radiotherapy in benign diseases like GO. A retrospective study indicated that late OR in patients with long-lasting active GO may improve diplopia and visual acuity, decreasing disease activity. Our case report supports this conclusion., Conclusions: This report and literature review underscores the importance of considering late OR combined with intravenous methylprednisolone as a viable treatment option for GO patients with prolonged disease activity, emphasizing the crucial role of personalized therapy in managing GO. However, further investigations are warranted to validate this approach in cases of long-lasting active GO., (© 2024. The Author(s).)

Published
2024
Full Text
View/download PDF

44. Bone densitometry in Thalassemia major: a closer look at pitfalls and operator-related errors in a 10-year follow-up population.

Author

Lucioni E, Pellegrino F, Remor D, Cossu A, Niero D, Longo F, Zatelli MC, Giganti M, Carnevale A, and Ambrosio MR

Subjects
Humans, Follow-Up Studies, Bone Density, Absorptiometry, Photon methods, Lumbar Vertebrae diagnostic imaging, beta-Thalassemia diagnostic imaging
Abstract

Purpose: Dual-energy X-ray absorptiometry (DXA) is the gold standard for measuring bone mineral density (BMD) with tolerable error rate, high precision, and excellent consistency. Our objective was to investigate the frequency and distribution of errors in a cohort of patients with Thalassemia major (TM)., Methods: We reviewed the DXA examinations of 340 patients with β-TM followed by our institution, acquired in different imaging centers between 2009 and 2019. We collected sex and age at the time of the first examination and at the last visit, as well as BMD, T-score, and Z-score values. Errors were analyzed by anatomical site (lumbar spine, total hip, femoral neck)., Results: Out of 5099 total DXA scans, 11.85% presented one or more errors. Specifically, the incorrect examinations were 315 out of 1707 (18.45%) at the lumbar spine level, 113 out of 1697 (6.66%) at the total hip, 176 out of 1695 (10.38%) at the femoral neck. Errors in vertebral inclusion were the most frequently registered (45.86%). A significant difference resulted from the comparison of the T-score and Z-score median values of all the lumbar spine DXA examinations and the correct ones (p value 0.037 and 0.0003, respectively)., Conclusion: Although not directly involved in the performance and interpretation of DXA, physicians interested in osteoporosis management should be familiar with the protocols to minimize errors and allow the proper use of bone densitometry. DXA obtained at the spine level is more frequently affected by errors in patients with TM, potentially influencing the diagnostic assessment of bone health status., (© 2024. Italian Society of Medical Radiology.)

Published
2024
Full Text
View/download PDF

45. Mixed mucinous adenocarcinoma/large cell neuroendocrine carcinoma of the uterine cervix: case report and molecular characterization of a rare entity.

Author

Fattorini C, Rocca BJ, Giusti A, Arganini M, Perotti B, Cavazzana A, Ambrosio MR, and Volante M

Subjects
Female, Humans, Middle Aged, Cervix Uteri pathology, Uterine Cervical Neoplasms genetics, Uterine Cervical Neoplasms pathology, Carcinoma, Neuroendocrine pathology, Adenocarcinoma pathology, Adenocarcinoma, Mucinous genetics
Abstract

Mixed neuroendocrine-non-neuroendocrine carcinomas of the cervix are rare and generally aggressive diseases. They often present at an advanced stage with hematogenous or lymphatic metastases. The prognosis is poor, mostly influenced by the neuroendocrine component. Unfortunately, the rarity of the disease caused a lack of information about its pathogenesis and molecular landscape. The latest guidelines recommend a multimodal approach that usually includes radical surgery, platinum/etoposide-based chemotherapy, or chemoradiation. Here, we are presenting a case of metastatic mixed adenocarcinoma-large cell neuroendocrine carcinoma of the cervix in a 49-year-old female patient. The molecular characterization of the lesion highlighted the ubiquitous presence of human papillomavirus-18 DNA both in the adenocarcinomatous and the neuroendocrine components, suggesting a role for the virus in the pathogenesis. Moreover, a different set of mutations was detected in the two parts, thus ruling out a possible clonal evolution of the neuroendocrine component from the adenocarcinoma one. More studies are needed to clarify the molecular landscape of these rare lesions and identify putative targets for therapy., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Published
2024
Full Text
View/download PDF

46. Radiomics in the characterization of lipid-poor adrenal adenomas at unenhanced CT: time to look beyond usual density metrics.

Author

Feliciani G, Serra F, Menghi E, Ferroni F, Sarnelli A, Feo C, Zatelli MC, Ambrosio MR, Giganti M, and Carnevale A

Subjects
Humans, Benchmarking, Tomography, X-Ray Computed, Lipids, Retrospective Studies, Radiomics, Adrenocortical Adenoma
Abstract

Objectives: In this study, we developed a radiomic signature for the classification of benign lipid-poor adenomas, which may potentially help clinicians limit the number of unnecessary investigations in clinical practice. Indeterminate adrenal lesions of benign and malignant nature may exhibit different values of key radiomics features., Methods: Patients who had available histopathology reports and a non-contrast-enhanced CT scan were included in the study. Radiomics feature extraction was done after the adrenal lesions were contoured. The primary feature selection and prediction performance scores were calculated using the least absolute shrinkage and selection operator (LASSO). To eliminate redundancy, the best-performing features were further examined using the Pearson correlation coefficient, and new predictive models were created., Results: This investigation covered 50 lesions in 48 patients. After LASSO-based radiomics feature selection, the test dataset's 30 iterations of logistic regression models produced an average performance of 0.72. The model with the best performance, made up of 13 radiomics features, had an AUC of 0.99 in the training phase and 1.00 in the test phase. The number of features was lowered to 5 after performing Pearson's correlation to prevent overfitting. The final radiomic signature trained a number of machine learning classifiers, with an average AUC of 0.93., Conclusions: Including more radiomics features in the identification of adenomas may improve the accuracy of NECT and reduce the need for additional imaging procedures and clinical workup, according to this and other recent radiomics studies that have clear points of contact with current clinical practice., Clinical Relevance Statement: The study developed a radiomic signature using unenhanced CT scans for classifying lipid-poor adenomas, potentially reducing unnecessary investigations that scored a final accuracy of 93%., Key Points: • Radiomics has potential for differentiating lipid-poor adenomas and avoiding unnecessary further investigations. • Quadratic mean, strength, maximum 3D diameter, volume density, and area density are promising predictors for adenomas. • Radiomics models reach high performance with average AUC of 0.95 in the training phase and 0.72 in the test phase., (© 2023. The Author(s).)

Published
2024
Full Text
View/download PDF

47. Cholecalciferol Use Is Associated With a Decreased Risk of Incident Morphometric Vertebral Fractures in Acromegaly.

Author

Chiloiro S, Frara S, Gagliardi I, Bianchi A, Giampietro A, Medici M, Allora A, di Filippo L, Ambrosio MR, Pontecorvi A, Zatelli MC, De Marinis L, and Giustina A

Subjects
Humans, Retrospective Studies, Cholecalciferol therapeutic use, Bone Density, Acromegaly complications, Acromegaly drug therapy, Spinal Fractures epidemiology, Spinal Fractures etiology, Spinal Fractures prevention & control
Abstract

Context: Skeletal fragility is observed in 30% to 60% of acromegaly patients, representing an emerging complication of the disease that increases disability. Despite several studies having investigated the clinical and hormonal prognostic factors for the occurrence of vertebral fractures (VFs) in acromegaly, very few data are available on their prevention/treatment including the effect of vitamin D (VD) supplementation, which has been reported to have a fracture-protective effect in several studies in patients with osteoporosis., Objective: We aimed to investigate the role of cholecalciferol (D3) supplementation in the prevention of incident VFs (i-VFs) in acromegaly., Methods: A longitudinal, retrospective and multicenter study was performed on 61 acromegaly patients treated and untreated with D3 supplementation., Results: Twenty-six patients were treated with D3 supplementation according to clinical guidelines. The median D3 weekly dosage was 8500 IU (interquartile range [IQR]: 3900). The median duration of D3 supplementation was 94 months (IQR: 38). At last follow-up, i-VFs were diagnosed in 14 patients (23%). I-VFs were less prevalent in patients on D3 supplementation (14.3% of cases) compared to patients not treated with D3 (85.7%; P = .02). The final level of serum V25OH-D was significantly lower in patients who developed i-VFs (28.6 ng/mL, IQR: 4.1) compared to patients who did not develop i-VFs (34.2 ng/mL, IQR: 9.6; P = .05). The logistic regression confirmed the protective role of D3 supplementation on the occurrence of i-VFs (odds ratio: 0.16; 95% CI, 0.03-0.79; P = .01)., Conclusion: It is likely that D3 supplementation could lead to a reduction in i-VFs in acromegaly., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society.)

Published
2023
Full Text
View/download PDF

48. Protein kinase C delta mediates Pasireotide effects in an ACTH-secreting pituitary tumor cell line.

Author

Gentilin E, Borges De Souza P, Ambrosio MR, Bondanelli M, Gagliardi I, and Zatelli MC

Subjects
Humans, Corticotrophs metabolism, Corticotrophs pathology, Protein Kinase C-delta metabolism, Protein Kinase C-delta pharmacology, Protein Kinase C-delta therapeutic use, Pro-Opiomelanocortin genetics, Pro-Opiomelanocortin metabolism, Pro-Opiomelanocortin pharmacology, Adrenocorticotropic Hormone metabolism, Neoplasm Recurrence, Local pathology, Cell Line, Cell Line, Tumor, Pituitary Neoplasms pathology, Pituitary ACTH Hypersecretion metabolism
Abstract

Purpose: Clinical control of corticotroph tumors is difficult to achieve since they usually persist or relapse after surgery. Pasireotide is approved to treat patients with Cushing's disease for whom surgical therapy is not an option. However, Pasireotide seems to be effective only in a sub-set of patients, highlighting the importance to find a response marker to this approach. Recent studies demonstrated that the delta isoform of protein kinase C (PRKCD) controls viability and cell cycle progression of an in vitro model of ACTH-secreting pituitary tumor, the AtT-20/D16v-F2 cells. This study aims at exploring the possible PRKCD role in mediating Pasireotide effects., Methods: It was assessed cell viability, POMC expression and ACTH secretion in AtT20/D16v-F2 cells over- or under-expressing PRKCD., Results: We found that Pasireotide significantly reduces AtT20/D16v-F2 cell viability, POMC expression and ACTH secretion. In addition, Pasireotide reduces miR-26a expression. PRKCD silencing decreases AtT20/D16v-F2 cell sensitivity to Pasireotide treatment; on the contrary, PRKCD overexpression increases the inhibitory effects of Pasireotide on cell viability and ACTH secretion., Conclusion: Our results provide new insights into potential PRKCD contribution in Pasireotide mechanism of action and suggest that PRKCD might be a possible marker of therapeutic response in ACTH-secreting pituitary tumors., (© 2023. The Author(s).)

Published
2023
Full Text
View/download PDF

49. Immune landscape and oncobiota in HPV-Associated Colorectal Cancer: an explorative study.

Author

Ambrosio MR, Niccolai E, Petrelli F, Di Gloria L, Bertacca G, Giusti A, Baldi S, Cavazzana A, Palmeri M, Perotti B, Ramazzotti M, Arganini M, and Amedei A

Subjects
Humans, RNA, Ribosomal, 16S, Tumor Microenvironment, Colorectal Neoplasms genetics, Papillomavirus Infections complications, Papillomavirus Infections epidemiology
Abstract

Worldwide more than 550,000 new patients suffering from malignant tumors are associated with human papillomaviruses (HPV) infection. However, only a small portion of patients infected progress to cancer, suggesting that other factors other than HPV may play a role. Some studies have investigated HPV infection in colorectal cancer (CRC) with discordant results; moreover, the role of HPV in CRC development is still unknown. We investigated HPV infection in 50 CRC from different regions, excluding the anal one, by immunohistochemistry (IHC), real-time PCR and RNA-seq. For each patient, we studied the tumor microenvironment in neoplastic and matched non-neoplastic samples, and we compared the tumor-infiltrating immune cell phenotypes among HPV-positive and negative samples. Finally, we compared the CRC-associated microbiota in HPV-positive and negative neoplastic samples by 16S rRNA sequencing. HPV infection was identified in 20% of CRC from the right side (caecum, ascending and transverse colon) and in 40% from the left side (descending colon and rectum). In all HPV-positive CRCs we found no expression of p53 and RB, thus suggesting HPV involvement in tumorigenesis. As far as the tumor microenvironment is concerned, in HPV-related cancers we observed a neoplastic environment with a reduced immune surveillance but an enhanced cytotoxic response by lymphocytes. HPV-positive and -negative CRC showed a different microbiota with lack of species normally found in CRC in the HPV-positive ones. Our results support the carcinogenic significance of HPV in CRC, suggesting a role of HPV in modulating the tumor immune microenvironment., (© 2023. The Author(s).)

Published
2023
Full Text
View/download PDF

50. Long-term low-dose tolvaptan efficacy and safety in SIADH.

Author

Bondanelli M, Aliberti L, Gagliardi I, Ambrosio MR, and Zatelli MC

Subjects
Humans, Tolvaptan adverse effects, Antidiuretic Hormone Receptor Antagonists adverse effects, Retrospective Studies, Benzazepines adverse effects, Sodium therapeutic use, Inappropriate ADH Syndrome drug therapy, Inappropriate ADH Syndrome complications, Hyponatremia etiology
Abstract

Purpose: Tolvaptan, a selective vasopressin V2-receptor antagonist, is approved for the treatment of SIADH-related hyponatremia, but its use is limited. The starting dose is usually 15 mg/day, but recent clinical experience suggests a lower starting dose (<15 mg/day) to reduce the risk of sodium overcorrection. However, long-term low-dose efficacy and safety has not been explored, so far. Aim of our study is to characterize safety and efficacy of long-term SIADH treatment with low-dose Tolvaptan., Methods: We retrospectively evaluated 11 patients receiving low-dose Tolvaptan (<15 mg/day) for chronic SIADH due to neurological, idiopathic and neoplastic causes. Plasma sodium levels were measured before and 1, 3, 5, 15 and 30 days after starting Tolvaptan and then at 3-month intervals. Anamnestic and clinical data were collected., Results: Mean time spanned 27.3 ± 29.8 months (range 6 months-7 years). Mean plasma sodium levels were within normal range 1, 3 and 6 months after starting Tolvaptan as well as after 1, 2, 3, 5 and 7 years of therapy. Neither osmotic demyelination syndrome nor overcorrection were observed. Plasma sodium levels normalization was associated with beneficial clinical effects. Neurological patients obtained seizures disappearance, improvement in neurological picture and good recovery from rehabilitation. Neoplastic patients were able to start chemotherapy and improved their general condition. Patients did not show hypernatremia during long-term follow-up and reported mild thirst and pollakiuria., Conclusions: The present study shows that long-term low-dose Tolvaptan is safe and effective in SIADH treatment. No cases of overcorrection were documented and mild side effects were reported., (© 2023. The Author(s).)

Published
2023
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results