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ABSTRACT: Background Hyponatraemia is the most frequent electrolyte disorder in hospitalized patients and has been associated with increased morbidity, mortality and length of hospital stay. There is evidence that also mild chronic hyponatraemia may have clinical consequences, such as gait disturbances, attention deficits, falls, increased risk of fractures and reduced bone mineral density. Nevertheless, this condition appears to be rather often not taken into consideration, or inappropriately managed and treated, thus negatively affecting patients' outcome. Aim The aim of this study was to investigate the awareness and management of hyponatraemia secondary to SIAD, a common cause of hyponatraemia, among Italian physicians (endocrinologists, nephrologists, internists) commonly involved as consultants. Methods A questionnaire, covering definition, diagnosis, management, treatment and prognosis of hyponatraemia secondary to SIAD, was developed with the support of the Italian Society of Endocrinology. Results Among the respondents (n = 275), the majority was aware of the negative implications of hyponatraemia or of an inappropriate treatment. Nevertheless, the answers indicated that SIAD is still underdiagnosed and incorrectly managed in clinical practice. In particular, only 47% of respondents used the validated biochemical parameters to diagnose hyponatraemia secondary to SIAD. The survey also indicated a rather satisfactory knowledge of the therapeutic options, including the currently available vasopressin receptor antagonists. Conclusions One of the main findings of the survey was that the diagnostic work-up of hyponatraemia still represents a critical issue. Therefore, there is urgent need of educational programs in order to improve the management of this condition and reduce morbidity, mortality and costs.
Journal of endocrinological investigation 04/2013; · 1.57 Impact Factor
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ABSTRACT: Background: Sleep apnea syndrome (SAS) is a frequent disorder in acromegalic patients and its frequency ranges from 45 to 87.5% of patients. Obstructive SAS is the prevailing form in acromegaly and its pathogenesis is based on craniofacial deformations and thickening of soft tissues and mucosas of upper airways and bronchi. Central and mixed types are less frequent. Respiratory complications, and SAS in particular, may contribute to the increased mortality observed in acromegaly. Aim: To assess the presence of SAS in acromegalic patients, its features and to correlate the severity of SAS with factors such as disease duration, body mass index (BMI), smoking, GH/IGF-1 serum levels, associated comorbidities. Subjects and methods: Polygraphy (SOMNOcheck® Effort Weinmann® V2.05) was performed in 25 consecutive acromegalic patients (9 men and 16 women). Statistical analysis was performed with Mann-Whitney's test and Spearman coefficient. Results: 14/25 patients (56%) were affected by SAS. The prevailing form was obstructive SAS (12/14 patients). Smoking, female gender and presence of lung disease appear to lead to a more severe form. We also found that the prevalence of hypertension was significantly higher in the group of patients with SAS, whereas no correlation was proved among SAS and disease duration, GH/IGF-1 serum levels, somatostatin analogs treatment, BMI and associated comorbidities. Conclusions: SAS is a frequent complication of acromegaly. Severe forms seem to be correlated with smoking and lung disease. Therefore, all acromegalic patients should be subjected to a polygraphic study for an early diagnosis and treatment and smoking should be discouraged.
Journal of endocrinological investigation 07/2012; · 1.57 Impact Factor
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M Filopanti,
L Olgiati,
G Mantovani,
S Corbetta,
M Arosio,
V Gasco,
L De Marinis,
C Martini,
F Bogazzi,
S Cannavò,
A Colao,
D Ferone,
G Arnaldi,
F Pigliaru, A Peri,
G Angeletti,
M L Jaffrain-Rea,
A G Lania,
A Spada
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ABSTRACT: The influence of full-length GH receptor (GHR) and exon 3-deleted GHR (d3GHR) on responsiveness to pegvisomant (PEG-V) in acromegalic patients is uncertain.
The aim of the study was to assess the distribution of GHR genotypes in a large series of patients on PEG-V therapy and their influence on treatment efficacy and adverse effects.
A cross-sectional multicenter pharmacogenetic study was conducted in 16 Italian endocrinology centers of major universities and tertiary care hospitals.
The study included 127 acromegalic patients enrolled from 2009 to 2010 not cured by previous surgery, radiotherapy, and long-acting somatostatin (SST) analogs, treated with PEG-V. INTERVENTION AND MAIN OUTCOME MEASURE: Sixty-three of 127 patients received combined PEG-V + SST analog therapy. Clinical and hormonal data at diagnosis and before and during PEG-V therapy were inserted in a database. GHR exon 3 deletion and other polymorphisms were genotyped by the coordinator center. Differences in PEG-V dosage required for IGF-I normalization and occurrence of adverse effects between carriers and noncarriers of GHR variants were evaluated.
d3GHR variants were not in Hardy-Weinberg equilibrium (P = 0.008). No association of these variants with PEG-V dose required for IGF-I normalization, adverse effects occurrence, and tumor regrowth was found in patients on PEG-V and on PEG-V + SST analog treatment. Similar data were obtained considering the GHR variant rs6180.
This study did not confirm a better response of d3GHR to PEG-V treatment in acromegaly. Other studies are needed to determine whether deviation from Hardy-Weinberg equilibrium may indicate an association of d3GHR genotype with poor response to usual treatments.
The Journal of clinical endocrinology and metabolism 12/2011; 97(2):E165-72. · 6.50 Impact Factor
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ABSTRACT: Thiazolidinediones (TZD), a class of anti-diabetic drugs, determine bone loss and increase fractures particularly in post-menopausal women, thus suggesting a protective role of sex steroids. We have previously demonstrated that the TZD rosiglitazone (RGZ) negatively affects bone mass by inhibiting osteoblastogenesis, yet inducing adipogenesis, in bone marrow-derived human mesenchymal stem cells (hMSC). The aim of this study was to determine whether estrogens and androgens are able to revert the effects of RGZ on bone. hMSC express estrogen receptor α and β and the androgen receptor. We found that 17β-estradiol (10 nM), the phytoestrogen genistein (10 nM), testosterone (10 nM) and the non-aromatizable androgens dihydrotestosterone (10 nM) and methyltrienolone (10 nM) effectively counteracted the adipogenic effect of RGZ (1 μM) in hMSC induced to differentiate into adipocytes, as determined by evaluating the expression of the adipogenic marker peroxisome proliferator-activated receptor γ and the percentage of fat cells. Furthermore, when hMSC were induced to differentiate into osteoblasts, all the above-mentioned molecules and also quercetin, another phytoestrogen, significantly reverted the inhibitory effect of RGZ on the expression of the osteogenic marker osteocalcin and decreased the number of fat cells observed after RGZ exposure. Our study represents, to our knowledge, the first demonstration in hMSC that androgens, independently of their aromatization, and estrogens are able to counteract the negative effects of RGZ on bone. Our data, yet preliminary, suggest the possibility to try to prevent the negative effects of TZD on bone, using steroid receptor modulators, such as plant-derived phytoestrogens, which lack evident adverse effects.
Journal of endocrinological investigation 05/2011; 35(4):365-71. · 1.57 Impact Factor
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G Parenti,
P C Cecchi,
B Ragghianti,
A Schwarz,
F Ammannati,
P Mennonna,
A Di Rita,
P Gallina,
N Di Lorenzo,
P Innocenti,
G Forti, A Peri
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ABSTRACT: Subarachnoid hemorrhage (SAH) is a potential cause of hypopituitarism. Most of the studies regarding the relationship between SAH and anterior pituitary function were retrospective and hormonal assessment was performed several months after SAH.
To prospectively evaluate the prevalence of anterior pituitary hormone deficiencies in the acute phase after spontaneous SAH and their possible correlation with clinical and radiological parameters.
Pituitary function was tested in 60 patients within 72 h after spontaneous SAH.
56.9% of the patients showed at least one anterior pituitary hormone deficiency: gonadotropin and GH secretion failure represented the most prevalent hormonal deficiencies (33.3 and 22.0%, respectively), whereas ACTH and TSH deficiency was less frequent (7.1 and 1.8%, respectively). With the exception of secondary hypogonadism, the prevalence of other pituitary hormone deficiencies is in agreement with previous studies, which evaluated pituitary function on longterm follow up after SAH. No correlation was found between hypopituitarism and clinical status, as assessed with Hunt-Hess and Glascow Coma Scales. Moreover, no correlation was found between hypopituitarism and bleeding severity evaluated with Fisher's scale.
We demonstrated a high prevalence of anterior pituitary hormone deficiencies acutely after SAH. Although part of GH and gonadotropin deficiencies might be a consequence of functional alteration due to SAH itself, the finding of low cortisol levels in this stressful condition strongly suggests the presence of true hypocortisolism. Therefore, an evaluation of pituitary function shortly after SAH might be useful to identify a subset of patients who deserve a more accurate follow-up.
Journal of endocrinological investigation 05/2011; 34(5):361-5. · 1.57 Impact Factor
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ABSTRACT: The syndrome of inappropriate ADH secretion (SIADH), also recently referred to as the "syndrome of inappropriate antidiuresis", is an often underdiagnosed cause of hypotonic hyponatremia, resulting for instance from ectopic release of ADH in lung cancer or as a side-effect of various drugs. In SIADH, hyponatremia results from a pure disorder of water handling by the kidney, whereas external Na+ balance is usually well regulated. Despite increased total body water, only minor changes of urine output and modest edema are usually seen. Renal function and acid-base balance are often preserved, while neurological impairment may range from subclinical to life-threatening. Hypouricemia is a distinguishing feature. The major causes and clinical variants of SIADH are reviewed, with particular emphasis on iatrogenic complications and hospital-acquired hyponatremia. Effective treatment of SIADH with water restriction, aquaretics, or hypertonic saline + loop diuretics, as opposed to worsening of hyponatremia during parenteral isotonic fluid administration, underscores the importance of an early accurate diagnosis and careful follow-up of these patients.
Journal of endocrinological investigation 10/2010; 33(9):671-82. · 1.57 Impact Factor
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I Cellai,
G Petrangolini,
M Tortoreto,
G Pratesi,
P Luciani,
C Deledda,
S Benvenuti,
C Ricordati,
S Gelmini,
E Ceni,
A Galli,
M Balzi,
P Faraoni,
M Serio, A Peri
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ABSTRACT: Neuroblastoma (NB) is the most common extra-cranial solid tumour in infants. Unfortunately, most children present with advanced disease and have a poor prognosis. There is in vitro evidence that the peroxisome proliferator-activated receptor gamma (PPARgamma) might be a target for pharmacological intervention in NB. We have previously demonstrated that the PPARgamma agonist rosiglitazone (RGZ) exerts strong anti-tumoural effects in the human NB cell line, SK-N-AS. The aim of this study was to evaluate whether RGZ maintains its anti-tumoural effects against SK-N-AS NB cells in vivo.
For this purpose, tumour cells were subcutaneously implanted in nude mice, and RGZ (150 mg kg(-1)) was administered by gavage daily for 4 weeks. At the end of treatment, a significant tumour weight inhibition (70%) was observed in RGZ-treated mice compared with control mice. The inhibition of tumour growth was supported by a strong anti-angiogenic activity, as assessed by CD-31 immunostaining in tumour samples. The number of apoptotic cells, as determined by cleaved caspase-3 immunostaining, seemed lower in RGZ-treated animals at the end of the treatment period than in control mice, likely because of the large tumour size observed in the latter group.
To our knowledge, this is the first demonstration that RGZ effectively inhibits tumour growth in a human NB xenograft and our results suggest that PPARgamma agonists may have a role in anti-tumoural strategies against NB.
British Journal of Cancer 02/2010; 102(4):685-92. · 5.04 Impact Factor
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A Di Mambro,
C Giuliani,
F Ammannati,
E Mannucci,
S Scoccianti,
B Detti,
I Meattini,
P Mennonna,
G Forti,
M Serio, A Peri
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ABSTRACT: Radiotherapy may be used as an adjuvant treatment of pituitary adenomas. The aim of our study was to present our experience of multimodal treatment of pituitary adenomas, consisting in temporary implantation of (192)Ir-labeled wires following transphenoidal surgery.
An observational investigation was performed on a series of 80 patients undergoing surgery (S) for pituitary adenomas between 1982 and 2000, some of whom received post-operative external beam radiotherapy (EBRT) (no.=19 between 1982 and 1990), brachytherapy (B) (no.=35, all after 1991), or both irradiation modalities (EBRT+B) (no.=14). The different treatments were compared in terms of hormonal normalization in the subgroup of patients with hypersecreting adenomas, tumor control, and side effects.
Hormonal normalization was obtained in 84% of S+B patients and in 61% of S+EBRT patients. Tumor control was obtained in 74.3% of S+B patients and in 63.1% of S+EBRT patients. Anterior pituitary hormones deficits ranged from 8.6-34% in S+B patients and from 15.8-47.4% in S+EBRT patients, after a mean follow-up of 14 yr. The latter group also showed a higher rate of multiple deficits (42.1% vs 22.8%). Diabetes insipidus and other major complications were rare events in all groups.
We presented one original experience regarding brachytherapy in the management of pituitary tumors, which turned out to be effective and safe. Additional prospective, and possibly randomized, studies should clarify whether in the era of 3-dimensional conformal radiotherapy and stereotactic radiotherapy this treatment modality may still have a role.
Journal of endocrinological investigation 12/2009; 33(7):455-60. · 1.57 Impact Factor
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S Benvenuti,
P Luciani,
I Cellai,
C Deledda,
S Baglioni,
R Saccardi,
S Urbani,
F Francini,
R Squecco,
C Giuliani,
G B Vannelli,
M Serio,
A Pinchera, A Peri
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ABSTRACT: Thyroid hormones (TH) play an important role in the development of human brain, by regulating the expression of specific genes. Selective Alzheimer's disease indicator-1 (seladin-1) is a recently discovered gene with neuroprotective properties, which has been found to be down-regulated in brain regions affected by Alzheimer's disease. Seladin-1 has anti-apoptotic properties mainly due to the inhibition of the activation of caspase 3. The aim of this study was to determine whether seladin-1 may be regarded as a new mediator of the effects of TH in the developing brain. In order to demonstrate this hypothesis, the effects of TH both on cell differentiation and on the expression of seladin-1 were assessed in two different cell models, i.e. fetal human neuroepithelial cells (FNC) and human mesenchymal stem cells (hMSC), which can be differentiated into neurons. 3,3',5-Triiodothyronine (T3) determined different biological responses (inhibition of cell adhesion, induction of migration, and increase in the expression of the neuronal marker neurofilament-M and Na+ and Ca2+ channel functionality) in both FNC and hMSC, which express TH receptors. Then, we showed that TH significantly increase the expression levels of seladin-1, and that T3 effectively prevents camptothecin-induced apoptosis. However, in hMSC-derived neurons the expression of seladin-1 was not affected by TH. Our results demonstrated for the first time that seladin-1 is a novel TH-regulated gene in neuronal precursors. In view of its anti-apoptotic activity, it might be hypothesized that one of the functions of the increased seladin-1 levels in the developing brain may be to protect neuronal precursor cells from death.
Journal of Endocrinology 06/2008; 197(2):437-46. · 3.55 Impact Factor
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M Filopanti,
A M Barbieri,
A R Angioni,
A Colao,
V Gasco,
S Grottoli, A Peri,
S Baglioni,
M F Fustini,
F Pigliaru, [......],
G Borretta,
B Ambrosi,
M L Jaffrain-Rea,
M Gasperi,
S Brogioni,
S Cannavò,
G Mantovani,
P Beck-Peccoz,
A Lania,
A Spada
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ABSTRACT: Dopamine-agonist cabergoline (CB) reduces prolactin (PRL) secretion and tumor size in 80% of patients with prolactin-secreting adenomas (PRL-omas) by binding type 2 dopamine receptor (DRD2). The mechanisms responsible for resistance to CB remain largely unknown. To assess the association of DRD2 with sensitivity to CB, TaqI-A1/A2, TaqI-B1/B2, HphI-G/T and NcoI-C/T genotypes were determined in a cross-sectional retrospective study, including 203 patients with PRL-oma. DRD2 alleles frequencies did not differ between patients and 212 healthy subjects. Conversely, NcoI-T allele frequency was higher in resistant rather than responsive patients, considering both PRL normalization (56.6 vs 45.3%, P=0.038) and tumor shrinkage (70.4 vs 41.4%, P=0.006). Finally, [TaqI A1-/TaqI B1-/HphI T-/NcoI T-] haplotype was found in 34.5% of patients normalizing PRL with < or =3 mg/week of CB vs 11.3% of resistants (P=0.021). In conclusion, resistance to CB was associated with DRD2 NcoI-T+ allele, consistent with evidence suggesting that this variant may lead to reduction and instability of DRD2 mRNA or protein.
The Pharmacogenomics Journal 04/2008; 8(5):357-63. · 4.54 Impact Factor
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S Benvenuti,
I Cellai,
P Luciani,
C Deledda,
S Baglioni,
C Giuliani,
R Saccardi,
B Mazzanti,
S Dal Pozzo,
E Mannucci, A Peri,
M Serio
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ABSTRACT: Thiazolidinediones (TZD) are widely prescribed for the treatment of Type 2 diabetes. Increased loss of bone mass and a higher incidence of fractures have been associated with the use of this class of drugs in post-menopausal women. In vitro studies performed in rodent cell models indicated that rosiglitazone (RGZ), one of the TZD, inhibited osteoblastogenesis and induced adipogenesis in bone marrow progenitor cells. The objective of the present study was to determine for the first time the RGZ-dependent shift from osteoblastogenesis toward adipogenesis using a human cell model. To this purpose, bone marrow-derived mesenchymal stem cells were characterized and induced to differentiate along osteogenic and adipogenic lineages. We found that the exposure to RGZ potentiated adipogenic differentiation and shifted the differentiation toward an osteogenic phenotype into an adipogenic phenotype, as assessed by the appearance of lipid droplets. Accordingly, RGZ markedly increased the expression of the typical marker of adipogenesis fatty-acid binding protein 4, whereas it reduced the expression of Runx2, a marker of osteoblastogenesis. This is the first demonstration that RGZ counteracts osteoblastogenesis and induces a preferential differentiation into adipocytes in human mesenchymal stem cells.
Journal of endocrinological investigation 11/2007; 30(9):RC26-30. · 1.57 Impact Factor
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I Cellai,
S Benvenuti,
P Luciani,
A Galli,
E Ceni,
L Simi,
S Baglioni,
M Muratori,
B Ottanelli,
M Serio,
C J Thiele, A Peri
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ABSTRACT: Neuroblastoma (NB) is the most common extracranial solid tumour in infants. Unfortunately, most children present with advanced disease and have a poor prognosis. In the present study, we evaluated the role of the peroxisome proliferator-activated receptor gamma (PPARgamma) agonist rosiglitazone (RGZ) in two NB cell lines (SK-N-AS and SH-SY5Y), which express PPARgamma. Rosiglitazone decreased cell proliferation and viability to a greater extent in SK-N-AS than in SH-SY5Y. Furthermore, 20 microM RGZ significantly inhibited cell adhesion, invasiveness and apoptosis in SK-N-AS, but not in SH-SY5Y. Because of the different response of SK-N-AS and SH-SY5Y cells to RGZ, the function of PPARgamma as a transcriptional activator was assessed. Noticeably, transient transcription experiments with a PPARgamma responsive element showed that RGZ induced a three-fold increase of the reporter activity in SK-N-AS, whereas no effect was observed in SH-SY5Y. The different PPARgamma activity may be likely due to the markedly lower amount of phopshorylated (i.e. inactive) protein observed in SK-N-AS. To our knowledge, this is the first demonstration that the differential response of NB cells to RGZ may be related to differences in PPARgamma transactivation. This finding indicates that PPARgamma activity may be useful to select those patients, for whom PPARgamma agonists may have a beneficial therapeutic effect.
British Journal of Cancer 11/2006; 95(7):879-88. · 5.04 Impact Factor
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ABSTRACT: Pituitary adenomas may be the cause of the syndrome of inappropriate secretion of antidiuretic hormone (SIADH), although few cases have so far been reported. We described a case of hypotonic hyponatremia in a 76-yr-old man with a pituitary macroadenoma. He had a recent history of two syncopal attacks which had occurred in the last two months. Baseline assessment demonstrated a sodium serum level of 114 mEq/l. Clinically, the patient appeared euvolemic. Thyroid and adrenal function testing did not show any abnormality. Plasma and urinary osmolality (238 and 186 mOsm/kg, respectively) were in agreement with the diagnosis of SIADH. Accordingly, 3% hypertonic saline solution was started, followed by water intake restriction when natremia reached 126 mEq/l. A computed tomography (CT) scan of the chest revealed the presence of a 2-cm lesion in the azygos-esophageal recess. Because the nature of the lesion appeared uncertain, antibiotic therapy was initiated. After one month, a new CT scan did not show any evidence of the mediastinic mass. Sodium serum level was within the normal range (141 mEq/l) and remained stable thereafter, without fluid restriction. This case very well demonstrates that, in the presence of hyponatremia due to SIADH, more frequently associated co-morbidities (ie mediastinic diseases) have to be searched, even in the presence of a possible, yet rare, cause of this syndrome (ie pituitary adenoma).
Journal of endocrinological investigation 10/2006; 29(8):750-3. · 1.57 Impact Factor
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E Ferrante,
C Pellegrini,
S Bondioni,
E Peverelli,
M Locatelli,
P Gelmini,
P Luciani, A Peri,
G Mantovani,
S Bosari,
P Beck-Peccoz,
A Spada,
A Lania
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ABSTRACT: Somatostatin analogs currently used in the treatment of acromegaly and other neuroendocrine tumors inhibit hormone secretion and cell proliferation by binding to somatostatin receptor type (SST) 2 and 5. The antiproliferative pathways coupled to these receptors have been only partially characterized. The aim of this study was to evaluate the effect of octreotide and super selective SST2 (BIM23120) and SST5 (BIM23206) analogs on apoptotic activity and apoptotic gene expression in human somatotroph tumor cells. Eight somatotroph tumors expressing similar levels of SST2 and SST5 evaluated by real-time PCR and western blot analyses were included in the study. In cultured cells obtained from these tumors, octreotide induced a dose-dependent increase of caspase-3 activity (160+/-20% vs basal at 10 nM) and cleaved cytokeratin 18 levels (172+/-25% vs basal) at concentrations higher than 0.1 nM. This effect was due to SST2 activation since BIM23120 elicited comparable responses, while BIM23206 was ineffective. BIM23120-stimulated apoptosis was dependent on phosphatases, since it was abrogated by the inhibitor orthovanadate, and independent from the induction of apoptosis-related genes, such as p53, p63, p73, Bcl-2, Bax, BID, BIK, TNFSF8, and FADD. In somatotroph tumors, both BIM23120 and BIM2306 caused growth arrest as indicated by the increase in p27 and decrease in cyclin D1 expression. In conclusion, the present study showed that octreotide-induced apoptosis in human somatotroph tumor cells by activating SST2. This effect, together with the cytostatic action exerted by both SST2 and SST5 analogs, might account for the tumor shrinkage observed in acromegalic patients treated with long-acting somatostatin analogs.
Endocrine Related Cancer 10/2006; 13(3):955-62. · 4.36 Impact Factor
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I Cellai,
S Benvenuti,
P Luciani,
A Galli,
E Ceni,
L Simi,
S Baglioni,
M Muratori,
B Ottanelli,
M Serio,
C J Thiele, A Peri
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ABSTRACT: Materials and methods Results Discussion References Acknowledgements Figures and TablesNeuroblastoma (NB) is the most common extracranial solid tumour in infants. Unfortunately, most children present with advanced disease and have a poor prognosis. In the present study, we evaluated the role of the peroxisome proliferator-activated receptor (PPAR) agonist rosiglitazone (RGZ) in two NB cell lines (SK-N-AS and SH-SY5Y), which express PPAR. Rosiglitazone decreased cell proliferation and viability to a greater extent in SK-N-AS than in SH-SY5Y. Furthermore, 20 M RGZ significantly inhibited cell adhesion, invasiveness and apoptosis in SK-N-AS, but not in SH-SY5Y. Because of the different response of SK-N-AS and SH-SY5Y cells to RGZ, the function of PPAR as a transcriptional activator was assessed. Noticeably, transient transcription experiments with a PPAR responsive element showed that RGZ induced a three-fold increase of the reporter activity in SK-N-AS, whereas no effect was observed in SH-SY5Y. The different PPAR activity may be likely due to the markedly lower amount of phopshorylated (i.e. inactive) protein observed in SK-N-AS. To our knowledge, this is the first demonstration that the differential response of NB cells to RGZ may be related to differences in PPAR transactivation. This finding indicates that PPAR activity may be useful to select those patients, for whom PPAR agonists may have a beneficial therapeutic effect.Keywords: PPAR, rosiglitazone, neuroblastoma
British Journal of Cancer 09/2006; 95(7):879-888. · 5.04 Impact Factor
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ABSTRACT: Among the geriatric population, there is a lower incidence of thyroid carcinoma (TC), but it accounts for 30% of all thyroid disorders compared to 6-8% in younger subjects. Prognosis, moreover, is worse in the elderly, as demonstrated by the fact that 81% of deaths related to these tumors occur in patients over 55. The aim of this retrospective study was to identify the characteristics of differentiated thyroid carcinoma (DTC) peculiar to the elderly.
Of 638 patients who underwent surgery for DTC over a period of 30 years, 46 were more than 70 years old. All the elderly patients had undergone radioioidine and TSH-suppression therapy following surgical resection.
Despite these measures, the rate of recurrence was 26.5% at 5 years and 63.6% at 10 years. The 5- and 10-year disease-specific survival rates were 87.8% and 63.6%, respectively. On an average, survival was 55.1 months when death was disease-related, and with regard to histological type, it was longer in papillary carcinoma than in the follicular variant, and longest of all in occult sclerosing carcinoma. Survival was greatest in patients with tumors less than 2 cm in diameter, characterized by the absence of extraglandular spread and by lymph node metastasis.
Journal of Surgical Oncology 04/2006; 93(3):194-8. · 2.10 Impact Factor
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G Parenti,
R Nassi,
S Silvestri,
S Bianchi,
A Valeri,
G Manca,
S Mangiafico,
F Ammannati,
M Serio,
M Mannelli, A Peri
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ABSTRACT: The diagnosis of Cushing's syndrome (CS) may sometimes be cumbersome. In particular, in ACTH-dependent CS it may be difficult to distinguish between the presence of an ACTH-secreting pituitary adenoma and ectopic ACTH and/or CRH secretion. In such instances, the etiology of CS may remain unknown despite extensive diagnostic workout, and the best therapeutic option for each patient has to be determined. We report here the case of a 54-yr-old man affected by ACTH-dependent CS in association with a left adrenal adenoma and medullary thyroid carcinoma (MTC). He presented with clinical features and laboratory indexes of hypercortisolism associated with elevated levels of calcitonin. Ectopic CS due to MTC was reported previously. In our case hypercortisolism persisted after surgical treatment of MTC. Thorough diagnostic assessment was performed, in order to define the aetiology of CS. He was subjected to basal and dynamic hormonal evaluation, including bilateral inferior petrosal sinus sampling. Extensive imaging evaluation was also performed. Overall, the laboratory data together with the results of radiological procedures suggested that CS might be due to inappropriate CRH secretion. However, the source of CRH secretion in this patient remained unknown. It was then decided to remove the left adenomatous adrenal gland. Cortisol level fell and has remained within the normal range nine months after surgery. This case well depicts the complexity of the diagnostic workout, which is needed sometimes to correctly diagnose and treat CS, and suggests that monolateral adrenalectomy may represent, at least temporarily, a reasonable therapeutic option in occult ACTH-dependent hypercortisolism.
Journal of endocrinological investigation 03/2006; 29(2):177-81. · 1.57 Impact Factor
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M Filopanti,
C Ronchi,
E Ballarè,
S Bondioni,
A G Lania,
M Losa,
S Gelmini, A Peri,
C Orlando,
P Beck-Peccoz,
A Spada
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ABSTRACT: The aim of the study was to investigate the possible correlation of single nucleotide polymorphisms in somatostatin receptor (SSTR)2 and SSTR5 genes with the responsiveness to somatostatin analogs in a cohort of acromegalic patients.
Three single nucleotide polymorphisms (a-83 g, c-57 g, and t80c) of SSTR2 and three (t-461c, c325t, and c1004t) of SSTR5 were analyzed in 66 acromegalic patients with different responsiveness to somatostatin analogs and 66 healthy controls.
Allele frequencies in patients and controls were similar. No association between SSTR2 genotypes and GH and IGF-I levels was found. When considering SSTR5 variants, patients homozygous or heterozygous for the substitution c1004 (P+) showed basal IGF-I levels significantly lower than patients homozygous for 1004t (P-). Moreover, serum GH levels were lower in patients with P+/T- haplotype (having c1004 allele and no t-461 allele) than in those with P-/T+. No correlation between SSTR2 and SSTR5 genotypes, responsiveness to somatostatin therapy, and mRNA expression in the removed adenomas (n = 10) was found.
These data suggest a role for SSTR5 t-461c and c1004t alleles in influencing GH and IGF-I levels in patients with acromegaly, whereas SSTR2 and SSTR5 variants seem to have a minor role in determining the responsiveness to somatostatin analogs.
Journal of Clinical Endocrinology & Metabolism 09/2005; 90(8):4824-8. · 6.50 Impact Factor
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ABSTRACT: Experimental evidence indicates that estrogen exerts neuroprotective effects. According to the fact that Alzheimer's disease (AD) is more common in post-menopausal women, estrogen treatment has been proposed. However, the beneficial effect of estrogen or selective estrogen receptor modulators (SERMs) in preventing or treating AD is a controversial issue, which will be summarized in this review. Recently, a novel gene, named selective AD indicator-1 (seladin-1), has been isolated and found to be down-regulated in brain regions affected by AD. Seladin-1, which is considered the human homolog of the plant protein DIMINUTO/DWARF1, confers protection against beta-amyloid-mediated toxicity and from oxidative stress and is an effective inhibitor of caspase 3 activity, a key mediator of apoptosis. This review will present the up-to-date findings regarding seladin-1 and DIMINUTO/DWARF1. In addition, the possibility that seladin-1 may be a downstream effector of estrogen receptor activation in the brain, based on our recent experimental findings using a human fetal neuronal model, will be addressed.
Journal of endocrinological investigation 04/2005; 28(3):285-93. · 1.57 Impact Factor
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M Filopanti,
E Ballarè,
A G Lania,
S Bondioni,
U Verga,
M Locatelli,
L M Zavanone,
M Losa,
S Gelmini, A Peri,
C Orlando,
P Beck-Peccoz,
A Spada
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ABSTRACT: SS receptor types 2 and 5 (sst2 and sst5) are involved in the control of secretion and proliferation of normal and tumoral somatotrophs and thyrotrophs. The mechanisms leading to reduced responsiveness to SS analogues in patients with pituitary tumors are poorly understood. The aim of the study was to verify the possible loss of heterozygosity (LOH) at the sst5 gene locus in somatotroph and thyrotroph adenomas by screening leukocyte and tumor DNA for two single nucleotide polymorphisms, i.e. C1004T leading to P335L change and T-461C in the 5'-upstream region. Among the 13 informative samples, 1 GH- and 1 TSH-secreting adenoma showed LOH at sst5 gene locus with the retention of Leu335 variant. By analyzing other polymorphic markers spanning from telomere to 16p13.3-13.2 boundaries, DNA deletion of at least 1 megabase was found in both tumors. LOH in thyrotroph adenoma was associated with unusual tumor aggressiveness that required a second surgery and resistance to SS analogs, while no obvious phenotype was identified in the case of the somatotroph adenoma. In conclusions, LOH at the sst5 gene locus is a rare phenomenon, occurring in about 10% of pituitary tumors, that seems to be associated with an aggressive phenotype, at least in thyrotroph adenomas. Further studies are required to confirm this association and to identify the genes, in addition to sst5, lost in these tumors.
Journal of endocrinological investigation 12/2004; 27(10):937-42. · 1.57 Impact Factor
