Biomedical subjects

Emilio Fiore

Publications and source records attributed to Emilio Fiore.

3 recordsLinked to original sources

PubMed2006

Testicular function after 131I therapy for hyperthyroidism.

OBJECTIVE: Radioiodine-131 is commonly used for treatment of hyperthyroidism but there are few available data on the effects of this treatment on male gonadal function. The untoward effects of (131)I have been mainly studied in male patients treated with high doses for thyroid cancer. In the present work we studied the absorbed radiation dose to the testes and testicular function in hyperthyroid men after (131)I treatment. PATIENTS AND MEASUREMENTS: Nineteen male hyperthyroid patients were enrolled in the study before (131)I therapy. Seventeen of the patients had Graves' disease and two had toxic adenoma. The study was subdivided into two parts: a dosimetric and a clinical study. Six patients were enrolled for the dosimetric study and 13 for the clinical study. The beta dose delivered to the testes was evaluated by the Medical Internal Radiation Dose (MIRD) method. The gamma dose was measured by thermoluminescent dosimeters (TLDs) placed on the skin overlying the inferior poles of the testes for 3 weeks after therapy. The clinical evaluation included hormone determination, ultrasound (US) of the testes and sperm analysis. Patients were followed up for 12 months after (131)I therapy. RESULTS: In the dosimetric study, the beta dose absorbed in the testes was 12.5 +/- 8.8 mGy (range 29-15 mGy) and the gamma dose was 15.8 +/- 5.3 mGy (range 24-11 mGy). The total dose to the testes for administered activity unit was 39 +/- 14 microGy/MBq (range 27-86 microGy/MBq). In the clinical study, FSH did not change significantly after (131)I treatment for the majority of patients. Serum testosterone (T) and the T/LH ratio were significantly reduced 45 days after treatment and returned to basal levels after 12 months. Ten out of 15 hyperthyroid patients (67%) had low sperm motility before treatment. A significant increase in progressive motility was observed after (131)I therapy (Friedman test chi(2) = 12.65, P = 0.01). Conversely, there was no significant variation in sperm concentration and percentage of normal forms after (131)I. CONCLUSIONS: After (131)I therapy, germinal epithelium and Leydig cell function undergo only marginal changes, which may have some significance in subjects with a pre-existing fertility impairment.

Adult↗

PubMed2002

Matrix metalloproteinase 9 (MMP-9/gelatinase B) proteolytically cleaves ICAM-1 and participates in tumor cell resistance to natural killer cell-mediated cytotoxicity.

Shedding of intercellular adhesion molecule 1 (ICAM-1) is believed to play a role in tumor cell resistance to cell-mediated cytotoxicity. However, the mechanism whereby ICAM-1 is shed from the surface of tumor cells remains unclear. In this study, we have addressed the possibility that matrix metalloproteinases are implicated in ICAM-1 shedding. Our observations suggest a functional relationship between ICAM-1 and matrix metalloproteinase 9 (MMP-9) whereby ICAM-1 provides a cell surface docking mechanism for proMMP-9, which, upon activation, proteolytically cleaves the extracellular domain of ICAM-1 leading to its release from the cell surface. MMP-9-dependent shedding of ICAM-1 is found to augment tumor cell resistance to natural killer (NK) cell-mediated cytotoxicity. Taken together, our observations propose a mechanism for ICAM-1 shedding from the cell surface and provide support for MMP involvement in tumor cell evasion of immune surveillance.

Cell Adhesion↗

PubMed2002

Induction of the interleukin-2/15 receptor beta-chain by the EWS-WT1 translocation product.

EWS-WT1 is a chimeric transcription factor resulting from fusion of the N-terminal domain of the Ewing sarcoma gene EWS to the three C-terminal zinc fingers of the Wilms tumor suppressor WT1. This translocation underlies desmoplastic small round cell tumor (DSRCT), which is noted for the abundance of reactive stroma surrounding islets of tumor cells, suggestive of paracrine signals contributing to tumor cell proliferation. Hybridization to high-density oligonucleotide microarrays can be used to identify targets of EWS-WT1. Expression of EWS-WT1 from a tetracycline-regulated promoter leads to the induction of growth-associated genes, of which the most remarkable is the beta-chain of the interleukin-2/15 receptor (IL-2/15Rbeta). Potent transcriptional activation by the chimeric protein maps to two bindings sites within the IL-2/15Rbeta promoter. Analysis of primary DSRCT tumor specimens demonstrates high levels of IL-2/15Rbeta within the tumor cells, along with expression of IL-2 and IL-15 by the abundant hyperplastic endothelial cells within the reactive stroma. Activation of this cytokine signaling pathway is consistent with the nuclear localization of its downstream effectors, phosphorylated STAT3 and STAT5. These observations suggest that the transcriptional induction of a cytokine receptor by a tumor-associated translocation product enables a proliferative response of epithelial cancer cells to ligands secreted by the surrounding stroma.

Abdominal Neoplasms↗