Biomedical subjects

Luciano Pezzullo

Publications and source records attributed to Luciano Pezzullo.

13 recordsLinked to original sources

PubMed2026

Network based approach identifies miR-145-3p as a central regulatory hub associated to the progression from localized to metastatic medullary thyroid carcinoma.

Medullary thyroid carcinoma (MTC) is a neuroendocrine tumor originating from calcitonin producing C-cells and accounts for 1-5% of thyroid cancers. Total thyroidectomy is curative in localized disease (N0), whereas lymph node metastases (N1) are associated with poorer prognosis. However, the molecular mechanisms driving the metastatic shift remain poorly understood. This study aimed to identify miRNA features linked to metastatic spread in MTC, focusing on the transition from N0 to N1. Co-expression networks were constructed for N0 and N1 tumors, and differential connectivity analysis was used to identify key miRNAs acting as regulatory hubs. Functional annotation of their target genes was performed using the Kyoto Encyclopedia of Genes and Genomes (KEGG), Gene Ontology (GO), and Reactome pathway analyses. Validation experiments were carried out in MTC cells to evaluate the effects of selected miRNAs on cell proliferation, survival, and MAPK pathway activation. Network analysis revealed distinct miRNA co-expression patterns between N0 and N1 tumors. Differential network analysis highlighted miR-145-3p as a central regulatory hub, exhibiting 29 altered co-expression changes and a marked loss of connectivity in N1. Target enrichment identified 59 validated genes, including key oncogenic drivers such as MYC, PTEN, BCL2, PIK3CA, AKT1, and MAPK7. In MTC cells, simultaneous inhibition of miR-145-3p together with its top co-expressed miRNAs increased proliferation and survival, and enhanced ERK phosphorylation, indicating MAPK pathway activation and a shift toward a more aggressive phenotype. In conclusion, this study identifies a miRNA regulatory hub centered on miR-145-3p that is associated with metastatic progression and highlights the value of network-based approaches in uncovering mechanisms of cancer dissemination. © 2026 The Author(s). The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

MAPK signaling↗

PubMed2006

The antiapoptotic protein BAG3 is expressed in thyroid carcinomas and modulates apoptosis mediated by tumor necrosis factor-related apoptosis-inducing ligand.

CONTEXT: We previously showed that BAG3 protein, a member of the BAG (Bcl-2-associated athanogene) co-chaperone family, modulates apoptosis in human leukemias. The expression of BAG3 in other tumor types has not been extensively investigated so far. OBJECTIVE: The objective of this study was to analyze BAG3 expression in thyroid neoplastic cells and investigate its influence in cell apoptotic response to TNF-related apoptosis-inducing ligand (TRAIL). DESIGN, SETTING, AND PATIENTS: We investigated BAG3 expression in human thyroid carcinoma cell lines, including NPA, and the effect of BAG3-specific small interfering RNA on TRAIL-induced apoptosis in NPA cells. Subsequently, we analyzed BAG3 expression in 30 benign lesions and 56 carcinomas from patients of the Naples Tumor Institute Fondazione Senatore Pascale. MAIN OUTCOME MEASURES: The main outcome measures were: analysis of BAG3 protein in NPA cells by Western blot and immunocytochemistry; analysis of apoptosis in TRAIL-stimulated NPA cells by flow cytometry; and evaluation of BAG3 expression in specimens from thyroid lesions by immunohistochemistry. RESULTS: BAG3 was expressed in human thyroid carcinoma cell lines; small interfering RNA-mediated downmodulation of its levels significantly (P < 0.0195) enhanced NPA cell apoptotic response to TRAIL. The protein was not detectable in 19 of 20 specimens of normal thyroid or goiters, whereas 54 of 56 analyzed carcinomas (15 follicular, 28 papillary, and 13 anaplastic) were clearly positive for BAG3 expression. CONCLUSIONS: BAG3 downmodulates the apoptotic response to TRAIL in human neoplastic thyroid cells. The protein is specifically expressed in thyroid carcinomas and not in normal thyroid tissue or goiter.

Adaptor Proteins, Signal Transducing↗

PubMed2006

Lhermitte-Duclos disease.

A 46-year-old female patient with previously recognized Graves' ophthalmopathy, underwent total thyroidectomy. After thyroid surgery exophthalmos worsened and signs unsteadiness of gait appeared. Magnetic resonance imaging showed a lesion in the basal portion of the left cerebellar hemisphere. Therefore, the patient underwent surgery. Pathological examination revealed dysplastic gangliocytoma of the cerebellum (Lhermitte-Duclos disease).

Cerebellar Neoplasms↗

PubMed2006

New molecular targeted therapies in thyroid cancer.

Carcinoma of the thyroid gland is the most common malignancy of the endocrine system. Differentiated tumors are often curable with surgical resection and radioactive iodine. A small percentage of such patients, however, do not undergo remission and need new therapeutic approaches. Both anaplastic and medullary thyroid carcinomas exhibit aggressive behavior and are usually resistant to current therapeutic modalities. Thyroid carcinoma represents a fascinating model and a particularly promising paradigm for targeted therapy because some of the key oncogenic events are activating mutations of genes coding for tyrosine kinases, and these occur early in cancer development. A prototype is the RET proto-oncogene, a receptor tyrosine kinase, which is a key regulator of development and a 'hotspot' for oncogenic mutations. Mutations in the RET proto-oncogene have been identified as causative for papillary carcinoma and familial medullary thyroid carcinoma, making it an attractive target for selective inhibition in these subtypes. ZD 6474 has shown promising activity in preclinical models against RET kinase, and its contemporary inhibition of vascular endothelial growth factor and epidermal growth factor pathways renders it a very attractive drug for clinical trials in thyroid cancer. Activating point mutation of B-RAF can occur early in the development of papillary carcinoma. Moreover, papillary carcinomas with these mutations have more aggressive properties and are diagnosed more often at an advanced stage. Clinical evaluation of B-RAF-targeting drugs is undergoing and trials in thyroid cancer are planned. Agents that restore radioiodine uptake, such as histone deacetylase inhibitors and retinoids, represent another exciting field in new drug development in thyroid cancer.

Antineoplastic Agents↗

PubMed2005

Huge parathyroid carcinoma: clinical considerations and literature review.

BACKGROUND: Parathyroid carcinoma is a rare malignancy, with an incidence of 0.5 to 4% of all cases of primary hyperparathyroidism. Surgery is the only curative treatment. CASE PRESENTATION: We report the case of a 66-year-old man referred for a large suspicious substernal goitre associated with severe hypercalcemia due to hyperparathyroidism. After normalization of serum calcium levels, patient underwent surgery. The voluminous cervicomediastinal firm mass could not be removed through the cervical incision; therefore a cervicothoracic approach was employed. Histopathology revealed a giant parathyroid cancer of 450 grams. A review of the literature was also undertaken to summarize the current treatment approaches for this rare malignancy. CONCLUSION: Parathyroid cancer is usually not recognized either preoperatively or intra-operatively. En bloc resection of the tumour with the adjacent tissue is the treatment of choice and it is very important to avoid the rupture of the capsule during operation. Neither tumour size, nor the lymph node status appears to play a role in prognosis. The management of parathyroid carcinoma is a challenge even for experienced surgeons.

Journal Article↗

PubMed2005

Complex regulation of the cyclin-dependent kinase inhibitor p27kip1 in thyroid cancer cells by the PI3K/AKT pathway: regulation of p27kip1 expression and localization.

Functional inactivation of the tumor suppressor p27(kip1) in human cancer occurs either through loss of expression or through phosphorylation-dependent cytoplasmic sequestration. Here we demonstrate that dysregulation of the PI3K/AKT pathway is important in thyroid carcinogenesis and that p27(kip1) is a key target of the growth-regulatory activity exerted by this pathway in thyroid cancer cells. Using specific PI3K inhibitors (LY294002, wortmannin, and PTEN) and a dominant active AKT construct (myrAKT), we demonstrated that the PI3K/AKT pathway controlled thyroid cell proliferation by regulating the expression and subcellular localization of p27. Results obtained with phospho-specific antibodies and with transfection of nonphosphorylable p27(kip1) mutant constructs demonstrated that PI3K/AKT-dependent regulation of p27(kip1) mislocalization in thyroid cancer cells occurred via phosphorylation of p27(kip1) at T157 and T198 (but not at S10 or T187). Finally, we evaluated whether these results were applicable to human tumors. Analysis of 100 thyroid carcinomas indicated that p27(kip1) phosphorylation at T157/T198 and cytoplasmic mislocalization were preferentially associated with activation of the PI3K/AKT pathway. Thus the PI3/AKT pathway and its effector p27(kip1) play major roles in thyroid carcinogenesis.

Androstadienes↗

PubMed2004

Complications of thyroid surgery: analysis of a multicentric study on 14,934 patients operated on in Italy over 5 years.

Complication rates associated with thyroid surgery can be evaluated only through analysis of case studies and follow-up data. This study covers postoperative data from 14,934 patients subjected to a follow-up of 5 years. Among them, 3130 (20.9%) underwent total lobectomy (TL), 9599 (64.3%) total thyroidectomy (TT), 1448 (9.7%) subtotal thyroidectomy with a monolateral remnant (MRST), and 757 (5.1%) subtotal thyroidectomy with bilateral remnants (BRST). A total of 6% of the patients had already been operated on. Persistent hypoparathyroidism occurred after 1.7% of all the operations, and temporary hypoparathyroidism was noted in 8.3%. Permanent palsy of the laryngeal recurrent nerve (LRN) occurred in 1.0% of patients, transient palsy in 2.0%, and diplegia in 0.4%. The superior laryngeal nerve was damaged in 3.7%; dysphagia occurred in 1.4% of cases, hemorrhage in 1.2%, and wound infection in 0.3%. No deaths were reported. A significant rate of LRN damage was noted, which has an important impact on the patient's social life. Hypoparathyroidism after total thyroidectomy is an important complication that can be successfully treated by therapy, although it is not always easily managed in special circumstances such as in young persons or pregnant women. The complications associated with thyroid surgery must be kept in mind so the surgeon can carefully evaluate the surgical and medical therapeutic options, have more precise surgical indications, and be able to give the patient adequate information.

Adult↗

PubMed2004

Thymosin beta-10 gene expression as a possible tool in diagnosis of thyroid neoplasias.

Overexpression of thymosin beta-10 (TB10) has been shown in rat thyroid transformed cell lines, and in human thyroid carcinoma tissues and cell lines. To investigate whether TB10 detection could be a valid tool in the diagnosis of human thyroid neoplasias, we extended the analysis of TB10 expression to a large number of thyroid hyperproliferative and neoplastic tissues using an immunohistochemical assay. Our analyses showed a TB10 positive staining in all human thyroid carcinomas particularly in the anaplastic histotypes, whereas no TB10 immunostaining was observed in normal thyroid, in adenomas and the majority of the goiters. These results suggest that the evaluation of TB10 gene expression may be considered a promising means of diagnosis of human thyroid hyperproliferative disorders.

Adenoma↗

PubMedDate not supplied

Giant desmoid tumor of the abdominal wall associated with familial adenomatous polyposis.

In this paper a case of vast desmoid tumor of the abdominal wall associated with familial adenomatous polyposis is reported. Desmoid tumors represent a particular type of fibrous neoplasms with a higher prevalence in females. They are extremely rare in the sporadic form, while they are found in about 10% of patients affected by familial adenomatous polyposis. Despite their benign histology and the absence of metastatic potential, they can be considered as fibrosarcomas with a low level of malignancy because of their locally invasive nature. The treatment of choice is surgical excision, as wide as possible, aimed at preventing recurrences, which are frequent in this tumor type. The usefulness of complementary therapies such as radiotherapy, hormone or chemotherapy, is not entirely clear.

Abdominal Neoplasms↗

PubMedDate not supplied

Risk of thyroid cancer and high prevalence of hepatitis C virus.

Some studies report an increased risk of autoimmune thyroid disease in hepatitis C and B as well as in interferon therapy. Recently a new link between HCV and papillary thyroid cancer has been published. The mechanism responsible for the oncogenetic role of HCV is not well understood, but it involves immunity system and autoimmunity disorders. We designed a case-control study on HCV exposure. To assess the positivity to HCV ELISA test and polymerize chain reaction technique (PCR) were used. For statistical analysis an odds ratio and corresponding 95% confidence intervals were computed using unconditional multiple-logistic-regression models. Our findings show a statistically significant association between HCV and papillary thyroid cancer (OR = 3.3, 95% CI 1.5-7.4, p=0.003), overall in female gender (OR = 3.3, 95% CI 1.2-8.7, p=0.01) and in the > or =50 years age category the risk for thyroid cancer was confirmed by the OR = 3.2 (95% CI 1.3-7.9, p=0.01). Based on our study there is an association between HCV and thyroid cancer and it is more readily detectable in countries with a high prevalence of HCV.

Adult↗

PubMedDate not supplied

[Complications of total thyroidectomy: incidence, prevention and treatment].

The range of indications for total thyroidectomy in the treatment of thyroid disease is steadily increasing, but any attempt to assess its real efficacy necessarily calls for a knowledge of the incidence of complications, amongst other things in order to provide the patient with complete information regarding the operation before obtaining his or her consent. Retrospective and observational analysis of 14,934 thyroidectomies performed in 42 Endocrine Surgery Units in Italy has made it possible to compare total thyroidectomy (TT) versus subtotal thyroidectomy with a bilateral remnant (ST-BR), subtotal thyroidectomy with a unilateral remnant (ST-UR) and total lobectomy-isthmectomy (TLI). The correlation between the number of total thyroidectomies and each of the other surgical procedures and the number of complications occurring with each of them was also assessed in order to quantify the effective risk of complications by determining the Odds Ratios on the basis of univariate analysis of the variables considered. The cases reviewed consisted of 9,599 TT (64%), 3,130 TLI (21%), 1,448 ST-UR (22%) and 757 ST-BR (5%); 13,023 (87%) cases were suffering from benign disease and 1,911 (13%) from malignancies. Recurrent laryngeal nerve injuries were present in 4.3% of the TT cases with 2.4% transient and 1.3% definitive (as against 3% in ST-BR and 2% in ST-UR with 1.4% and 1.1% transient, and 1% and 0.6% definitive, respectively; and 1.4% transient and 0.6% definitive in TLI). Hypocalcaemia after TT was transient in 14% and definitive in 2.2% (as against transient rates of 5% in ST-BR and ST-UR and 0.4 in TLI; and definitive hypocalcaemia in 0.6%, 0.8% and 0.07%, respectively). Haemorrhage occurred in 1.6% of TT cases (as against 2.1%, 0.5% and 0.4% in ST-BR, ST-UR and TLI, respectively). The Odds Ratios showed that TT presented a 16% higher complication rate than ST-UR which was assigned a value of 1, a 3% higher rate than ST-BR and a 5% lower rate than TLI. This greater incidence of complications with TT is attributable mainly to the greater incidence of transient hypoglycaemia and to a lesser extent to the slightly higher incidence of definitive hypoglycaemia, whereas the incidences of recurrent laryngeal nerve injuries were very similar in TT and ST-BR. Haemorrhagic complications were more frequent in ST-BR than in TT. Bearing in mind that TT is the absolute indication in the more demanding thyroid diseases (tumours, retrosternal goitre, Basedow's disease, recurrences) and in view of its fairly low complication rate, we believe that TT is a safe, reliable procedure, provided it is performed in a technically scrupulous manner. ST-BR is a technique which should be abandoned owing to the fact that its complication rate is comparable to that of TT and to the recurrences it may give rise to. ST-UR may be indicated if the surgeon is not sure of safeguarding the anatomical integrity of the recurrent nerve on one side.

Analysis of Variance↗

PubMedDate not supplied

Ultrasound contrast media in the study of salivary gland tumors.

BACKGROUND: The aims of the present study were: to assess standard ultrasound and color-Doppler patterns for the study and characterization of salivary gland tumors; to define the improvement in the color-Doppler ultrasound image after injection of a signal amplifier (Levovist); to compare morphological and vascular aspects of the neoplasm with data obtained during postoperative histopathological analysis. MATERIALS AND METHODS: We used color-Doppler ultrasound before and after injection of the contrast medium to study 56 patients (32 males and 24 females) between the ages of 28 and 77 years old, presenting nodular pathology of the salivary glands. Only patients with less than optimal results of the basic color-Doppler examination (grade of vascularization 0-1) were included in the study. The data were then compared with the final histological results. RESULTS: According to B-mode ultrasonography, all neoplasms were hypoechogenous; 8 showed irregular margins and, of these, 6 were carcinomas. We did not obtain significant data regarding size and echostructure. In 10 cases, we observed the presence of multiple locoregional formations in the lymph nodes. Patients were selected on the basis of unsatisfactory color-Doppler examination results; following injection of the contrast medium, we were able to visualize an increased number of vascular signals in 40 out of 56 patients, compared to the basic examination. This enabled us to better assess the vascular map of the neoplasms, as well as more easily trace the vascular blood flow and perform a better extrapolation of the quantitative and semi-quantitative data. This study demonstrated the importance of the vascular pattern, which is predictive of a malignant lesion when it is high-grade with multiple vascular poles and irregular vascular distribution. Furthermore, certain semi-quantitative parameters proved to be important, particularly the velocity of the systolic peak (SP), the cut-off of which was approximately 25 cm/s. The resistance index (RI) and pulsality index (PI) did not prove significant and showed overlapping values. CONCLUSION: We observed that the contrast medium was useful in characterizing lesions, of the salivary glands by allowing for a more precise vascular map of the lesions, as well as greater diagnostic accuracy in tracing the vascular blood flow and calculating quantitative and semiquantitative data.

Adenolymphoma↗

PubMedDate not supplied

[Diagnostic, therapeutic and healtcare management protocols in thyroid surgery. I consensus conference (UEC club)].

The aim of the study was to draw up a management protocol in thyroid surgery promoted by the Italian Association of Endocrine Surgery Units (Club delle UEC), shared by the experts and applied by the operators in the sector. The management protocols already presented in February 2002 and drawn up by the first Author of the present publication on the occasion of the current review were examined by the I Consensus Conference called on the topic by the Italian Endocrine Surgery Units. The conference comprised two distinct sessions, the first on 18 June 2005 within the framework of the 4th National Congress of the Club delle UEC in Naples, and the second on 17 September 2005 within the framework of the 8th Multidisciplinary Scanno Prize Meeting. A selected board of endocrinologists and endocrine surgeons, chaired by Aldo Pinchera and comprising the first nine Authors of this paper, examined the individual chapters in close collaboration with the other Authors, comparing their findings with the opinions of the experts cited in the text and submitting the consensus text for the approval of all those present. The diagnostic, therapeutic and healtcare management protocols in thyroid surgery approved by the I Consensus Conference are officially those proposed by the Italian Association of Endocrine Surgery Units (Club delle UEC) and are subject to review by October 1, 2007.

Clinical Protocols↗