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Biomedical subjects

Vincenzo Toscano

Publications and source records attributed to Vincenzo Toscano.

11 recordsLinked to original sources

3,5,3'-triiodothyronine (T3) is a survival factor for pancreatic beta-cells undergoing apoptosis.

3,5,3'-triiodothyronine (T3) is essential for the growth and the regulation of metabolic functions, moreover, the growth-stimulatory effect of T3 has largely been demonstrated and the pathways via which T3 promotes cell growth have been recently investigated. Type 1 diabetes (T1D) is due to the destruction of beta-cells, which occurs even through apoptosis. Aim of our study was to analyze whether T3 could have an antiapoptotic effect on cultured beta-cells undergoing apoptosis. We have demonstrated that T3 promotes cell proliferation in islet beta-cell lines (rRINm5F and hCM) provoking an increment in cell number (up to 55%: rRINm5F and 45%: hCM), cell viability, and BrdU incorporation, and regulating the cell cycle-related molecules (cyc A, D1, E, and p27(kip1)). T3 inhibited the apoptotic process induced by streptozocin, S-Nitroso-N-Acetylpenicylamine (SNAP), and H2O2 via regulation of the pro- and anti-apoptotic factors Bcl-2, Bcl-XL, Bad, Bax, and Caspase 3. The T3 protective effect was PI-3 K-, but not MAPK- or PKA-mediated, involving pAktThr308. Thus, T3 could be considered a survival factor protecting islet beta-cells from apoptosis.

Animals↗

Treatment of hirsutism and acne in hyperandrogenism.

Hirsutism and acne are common and highly distressing complaints in women with polycystic ovary syndrome (PCOS). Drugs are only partially effective on terminalized hairs, and removal of these hairs is usually required. Therefore, management of hirsutism is generally based upon a dual approach: a pharmacological therapy to reduce androgen secretion and/or androgen action, and removal of terminal hair already present. Ovarian suppression of androgen secretion with oral contraceptives is widely used in these women, but its efficacy appears limited. The most effective medical therapy for hirsutism is by anti-androgen drugs. Electrolysis and laser photothermolysis are considered the most effective cosmetic procedures, although the effects of these methods should not be considered permanent. Acne may be treated with different tools, according to the severity of the condition and other characteristics of the patient. These tools include topical and systemic retinoids and antibiotics, topical antibacterial agents, androgen suppression by oral contraceptives, and anti-androgen drugs.

5-alpha Reductase Inhibitors↗

3,5,3'-Triiodo-L-thyronine enhances the differentiation of a human pancreatic duct cell line (hPANC-1) towards a beta-cell-Like phenotype.

The thyroid hormone, 3,5,3'-Triiodo-L-thyronine (T3), is essential for growth, differentiation, and regulation of metabolic functions in multicellular organisms, although the specific mechanisms of this control are still unknown. In this study, treatment of a human pancreatic duct cell line (hPANC-1) with T3 blocks cell growth by an increase of cells in G(0)/G(1) cell cycle phase and enhances morphological and functional changes as indicated by the marked increase in the synthesis of insulin and the parallel decrease of the ductal differentiation marker cytokeratin19. Expression analysis of some of the genes regulating pancreatic beta-cell differentiation revealed a time-dependent increase in insulin and glut2 mRNA levels in response to T3. As last step of the acquisition of a beta-cell-like phenotype, we present evidence that thyroid hormones are able to increase the release of insulin into the culture medium. In conclusion, our results suggest, for the first time, that thyroid hormones induce cell cycle perturbations and play an important role in the process of transdifferentiation of a human pancreatic duct line (hPANC-1) into pancreatic-beta-cell-like cells. These findings have important implications in cell-therapy based treatment of diabetes and may provide important insights in the designing of novel therapeutic agents to restore normal glycemia in subjects with diabetes.

Carcinoma, Pancreatic Ductal↗

Thyroid tissue: US-guided percutaneous laser thermal ablation.

PURPOSE: To evaluate in vivo the safety and effectiveness of percutaneous laser thermal ablation (LTA) in the debulking of thyroid lesions. MATERIALS AND METHODS: Twenty-five adult patients at poor surgical risk with cold nodules (n = 8), autonomously hyperfunctioning thyroid nodules (n = 16), or anaplastic carcinoma (n = 1) underwent LTA. One to four 21-gauge spinal needles were inserted with ultrasonographic (US) guidance into the thyroid lesions. A 300-microm-diameter quartz optical fiber was advanced through the sheath of the needle. Nd:YAG laser was used with output power of 3-5 W. Side effects, complications, and clinical and hormonal changes were evaluated at the end of LTA and during follow-up. Linear regression analysis was used to investigate the correlation between energy delivered and reduction in nodule volume. Volume of induced necrosis and reduction in nodule volume were assessed with US or computed tomography. RESULTS: LTA was performed without difficulties in 76 LTA sessions. After treatment with 5 W, two patients experienced mild dysphonia, which resolved after 48 hours and 2 months. Improvement of local compression symptoms was experienced by 12 of 14 (86%) patients. Thyroid-stimulating hormone (TSH) was detectable in five of 16 (31%) patients with hyperfunctioning nodules at 6 months after LTA. Volume of induced necrosis ranged from 0.8 to 3.9 mL per session. Anaplastic carcinoma treated with four fibers yielded 32.0 mL of necrosis. Echo structure and baseline volume did not influence response. Energy load and reduction in nodule volume were significantly correlated (r(2) =.75, P <.001). Mean nodule volume reduction at 6 months in hyperfunctioning nodules was 3.3 mL +/- 2.8 (62% +/- 21.4 [SD]) and in cold nodules was 7.7 mL +/- 7.5 (63% +/- 13.8). CONCLUSION: LTA may be a therapeutic tool for highly selected problems in the treatment of thyroid lesions.

Adult↗

Percutaneous ethanol injection treatment in benign thyroid lesions: role and efficacy.

GOAL: To establish the role of percutaneous ethanol injection (PEI) treatment in benign thyroid lesions by evaluating: (1) the long-term efficacy and side effects of the treatment, (2) the factors predictive of efficacy of PEI, and (3) the cost effectiveness of the procedure. MATERIALS AND METHODS: Fifty-eight recurrent cystic nodules, 95 autonomously functioning nodules (AFTN), and 17 hyperfunctioning nodules causing thyrotoxicosis (toxic nodules) were treated by PEI from 1990 to 1996 in our center. Ultrasound (US) and color flow doppler (CFD) examinations were carried out before and after each treatment. In patients with AFTN, serum thyrotropin (TSH), free triiodothyronine (FT3), free thyroxine (FT4), thyroid peroxidase antibody (TPOAb) levels were tested before and after PEI. All patients were independently reexamined by two external reviewers after a minimum follow-up of 5 years (median, 6.9 years). RESULTS: The median number of treatments was 2.0 (range, 1.0-4.0) for cystic nodules, 4 (range, 2.0-6.0) for AFTN, and 5 (range, 3.0-7.0) for toxic nodules. At the 5-year evaluation cystic nodules showed a volume reduction greater than 75% versus baseline in 86.2% of cases and an improvement of local symptoms in 91.4% of cases. AFTN presented serum TSH within normal limits in 60.0% of patients. Toxic nodules showed a detectable serum TSH and normal FT3 and FT4 values in 35.3% of cases. Two cases of transient dysphonia were observed. In cystic lesions no significant correlation was found between the baseline and the final volume (r2 = 0.17) and no significant predictor of treatment efficacy was found. However, unilocularity was associated with a lower number of treatments than multilocularity (median, 2.0 vs. 3.0). Independent predictors of clinical efficacy in both AFTN and toxic nodules were a baseline volume less than 5.0 mL and a fluid component greater than 30% (odds ratio [OR] = 6.1 and 3.3, respectively). CONCLUSIONS: Most recurrent cystic lesions of the thyroid can be cured by PEI, which should become the first line of treatment. The majority of AFTN and toxic nodules with volume less than 5.0 mL presented a marked volume decrease and normal serum TSH levels when treated by PEI, which seems a valid alternative to clinical follow-up alone in patients refusing 131I. PEI is not indicated in large or toxic nodules, for which 131I is the treatment of choice.

Administration, Cutaneous↗

Mutational analysis of StAR gene in adrenal tumors.

Adrenal adenomas and carcinomas are mostly monoclonal, suggesting that a genetic alteration in a progenitor cell may contribute to their development. However, the molecular pathogenesis of these tumors still remains unclear. It has been already excluded that activating mutations of the ACTH receptor or of G protein stimulator alpha sub-units, affecting cAMP pathway, is involved in the tumorigenesis. Therefore, this work has been focused on post-transductional (ACTH) signal alterations and in particular on the mutational analysis of the Steroid Acute Regulatory protein (StAR) gene to verify whether somatic mutations or genomic polymorphisms of this gene may be correlated with adrenal tumorigenesis. Tissue DNA was extracted from 40 functional and non-functional adrenocortical tumors that were removed from patients aged between 17 and 72 years (mean 43 +/- 4). Blood DNA was obtained from 24 patients (aged between 26 and 70 years) affected by adrenal tumors and from 100 healthy subjects without radiological and clinical evidence of adrenal masses, aged between 25-35 years (90 Caucasians and 10 Africans). The DNA was used as the template for the amplification of the StAR gene using the polymerase chain reaction. The amplified DNA of each exon of the StAR gene was purified and sequenced in automatic sequenciator. With the exception of exon 5 showing in codon 203 an homozygous missense mutation, the sequence of the other exons of the StAR gene resulted normal in all tumors studied. The same homozygous mutation (Asp203Ala) was observed in the sequence of exon 5 performed on genomic DNA of the 24 affected patients and in the control subjects. The homozygosity of the mutation observed in all patients (either in tissue or blood samples) and in control subjects, independently of their ethnic origin, led us to suggest that the Asp203Ala cannot be considered as mutation or as polymorphism, but that it must be considered as a mistake in the sequence entered in the Genbank, which needs to be modified accordingly. These data, and those up to now reported in the literature, allow us to suggest that mutations of the gene coding for the protein involved in the initial step of the steroidogenesis could not be considered as a possible cause for the development of adrenal tumors.

Adenoma↗

Risk of malignancy in nonpalpable thyroid nodules: predictive value of ultrasound and color-Doppler features.

The aim of the study was to correlate the sonographic [ultrasound (US)] and color-Doppler (CFD) findings with the results of US-guided fine needle aspiration biopsy (FNA) and of pathologic staging of resected carcinomas to establish: 1) the relative importance of US features as risk factors of malignancy; and 2) a cost-effective management of nonpalpable thyroid nodules. Four hundred ninety-four consecutive patients with nonpalpable thyroid nodules (8-15 mm) were evaluated by US, CFD, and US-FNA. Ninety-two patients with inadequate cytology were excluded from the study. All patients with suspicious or malignant cytology underwent surgery, whereas subjects with benign cytology had clinical and US control 6 months later. Thyroid malignancies were observed in 18 of 195 (9.2%) solitary thyroid nodules and in 13 of 207 (6.3%) multinodular goiters. Cancer prevalence was similar in nodules greater or smaller than 10 mm (9.1 vs. 7.0%). Extracapsular growth (pT(4)) was present in 35.5%, and nodal involvement in 19.4% of neoplastic lesions, with no significant differences between tumors greater or smaller than 10 mm. At US cancers presented a solid hypoechoic appearance in 87% of cases, irregular or blurred margins in 77.4%, an intranodular vascular pattern in 74.2%, and microcalcifications in 29.0%. Irregular margins (RR 16.83), intranodular vascular spots (RR 14.29), and microcalcifications (RR 4.97) were independent risk factors of malignancy. FNA performed on hypoechoic nodules with at least one risk factor was able to identify 87% of the cancers at the expence of cytological evaluation of 38.4% of nonpalpable lesions. The majority of nonpalpable thyroid tumors can be identified by cytological evaluation of lesions presenting hypoechoic appearance in conjunction with one independent risk factor. Due to the nonnegligible prevalence of extracapsular growth and nodal metastasis, US-FNA should be performed on all 8-15 mm hypoechoic nodules with irregular margins, intranodular vascular spots or microcalcifications. Nonpalpable lesions of the thyroid without risk factors should be followed by means of clinical and US evaluation.

Adult↗

Is DD3 a new prostate-specific gene?

The search for new and more specific molecular markers of prostatic cancers has led, in recent years, to the identification of the DD3 gene. Using reverse transcription (RT)-PCR, we investigated DD3 gene expression in human cell lines, in blood samples from healthy men and women donors and in various neoplastic and non-neoplastic tissues from the prostate and other organs. Whereas RT-PCR analysis using primers that amplified the region spanning exons 1 and 3 yielded DD3 gene expression in all samples examined, a primer downstream to exon 4 detected the expected size DD3 band only in benign and malignant prostatic tissues. These findings indicate that the only prostate specific region of DD3 is exon 4.

Antigens, Neoplasm↗

Insulin-like growth factor (IGF)-I, IGF-II and IGF type I receptor (IGFR-I) expression in prostatic cancer.

Despite evidence implicating the insulin-like growth factor (IGF) system in the pathogenesis of prostate cancer, its precise role remains unclear. In this study we investigated the differential expression of IGF-I, IGF-II and their type I receptor (IGFR-I) in the epithelium and stroma of prostate neoplastic tissues. Using immunohistochemistry and in situ hybridization techniques, we analyzed 43 paraffin-embedded prostatic samples and compared prostatic cancer (Pca) with prostatic intraepithelial neoplasia (PIN) and its normal adjacent prostate (NAP) counterpart. We then determined a possible correlation of the immunohistochemical and in situ findings with two known prognostic clinical-pathological indices: Gleason score histological tumor grade and TNM clinical stage. In 22 of the 43 frozen prostatectomy specimens, IGF-I, IGF-II and IGFR-I mRNA expression were also evaluated by semiquantitative RT-PCR. Non neoplastic and neoplastic tissues examined contained detectable amounts of epithelial and stromal IGF-I, IGF-II and IGFR-I protein and mRNA; all levels increased significantly from normal tissue to PIN to Pca. In all three areas examined, IGFR-I expression was invariably higher in epithelium than in stroma, whereas expression of IGF ligands differed. In normal prostatic tissue, IGF-I and IGF-II expression was higher in stroma than in epithelium. Conversely, in Pca tissue, both factors were more strongly expressed in epithelial malignant cells. PIN areas showed IGF-I lowest, and IGF-II and IGFR-I levels highest in the epithelium. IGF-II protein and mRNA reached their highest levels in prostate tumors with high Gleason scores. These findings indicate that the IGF system changes as prostate tissue progresses from a normal to a malignant state. Differential expression of certain IGF system components in Pca may be associated with the malignant phenotype and more aggressive tumor behavior. Hence IGFs could serve to predict the outcome of prostatic cancer.

Aged↗

Simultaneous bilateral laparoscopic adrenalectomy is safe for synchronous large adrenal tumors.

Laparoscopy is now considered the gold standard for treating benign monolateral adrenal lesions. We present the case of a patient affected by Cushing's syndrome due to large bilateral adrenal adenomas (7.5 cm) who underwent simultaneous laparoscopic bilateral adrenalectomy. An anterior, lateral transperitoneal approach was used. Operative time was 200 minutes, and blood loss was 200 mL. No intraoperative complications were encountered. The postoperative course was uneventful, and the patient was discharged after 3 days. Laparoscopic bilateral adrenalectomy is a safe, effective procedure when performed by experienced hands and may be an alternative treatment for large adrenal lesions.

Adenoma↗