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Cinzia Giacometti

Publications and source records attributed to Cinzia Giacometti.

11 recordsLinked to original sources
PubMed2026

Integrated morphologic, immunophenotypic, and molecular profiling of advanced upper tract urothelial carcinoma across tumor compartments supports biopsy-based testing.

Upper tract urothelial carcinoma (UTUC) is an aggressive malignancy with limited molecular characterization in advanced disease. FGFR3 alterations are well established in low-grade urothelial carcinoma, but their prevalence, stability, and biological significance in locally advanced and metastatic UTUC remain only partially defined. We performed an integrated morphologic, immunohistochemical, and molecular analysis of 24 locally advanced and/or metastatic UTUC from 20 patients. FGFR3 status was assessed by RT-PCR across multiple tumor compartments, including biopsies, primary tumors, lymph-node metastases, and distant metastatic sites. Immunohistochemistry included CK20, CK5, GATA3, p53, and mismatch repair proteins. Targeted next-generation sequencing (NGS) was used to characterize co-occurring genomic alterations and to assess concordance with p53 immunophenotype. FGFR3 alterations were identified in 50% of patients and in 54.2% of analyzed tumors. FGFR3 status showed high intra-patient stability, with concordance between primary tumors and distant metastases in 90% of cases, whereas concordance with lymph node metastases was lower (50%), suggesting site-specific clonal divergence. Despite advanced stage, 92.3% of FGFR3-altered tumors displayed papillary urothelial carcinoma morphology, and most showed a luminal immunophenotype (61.5% by CK20/CK5 and 69.2% by GATA3/CK5). Targeted NGS revealed additional pathogenic alterations in 75% of patients, most frequently involving RTK/RAS/MAPK signaling (70%), cell-cycle regulation (25%), and PI3K/AKT pathway components (10%). TP53 mutations co-occurred with FGFR3 alterations in 60% of FGFR3-mutated patients and showed 90.4% concordance with p53 immunohistochemistry. Finally, a few cases exhibited complex, multi-site FGFR3 mutational patterns, consistent with intratumoral clonal evolutions. In conclusion, FGFR3 alterations are frequent and remarkably stable in advanced UTUC, even in high-grade and metastatic disease. These findings support the reliability of FGFR3 testing on limited diagnostic material and reinforce its relevance for therapeutic stratification. UTUC emerges as a molecularly dynamic disease in which early oncogenic drivers such as FGFR3 continue to shape tumor biology and therapeutic vulnerability at advanced stages.

Humans↗
PubMed2006

Extended tracheal resection for chondroma.

We report a case of a 43-year-old man who underwent an extended resection of the lower trachea for primary chondroma. Tracheal chondroma is a rare benign disease, arising from the cartilaginous rings, that grows intra-luminally or extends through the tracheal wall determining an obstructing syndrome. The endoscopy may be useful for diagnosis and palliative treatment, but the tracheal resection is recommended because the risk of recurrence or malignant transformation.

Adult↗
PubMed2006

Metabolic activity of rat hepatocytes cultured on homologous acellular matrix and transplanted into Gunn rats.

The metabolic activity of hepatocytes cultured on homologous acellular matrix (HAM) and transplanted into rats genetically incapable of bilirubin conjugation (Gunn rats) has been investigated. Hepatocytes from Wistar male rats were seeded on HAM and cultured for 9 days, and the proliferation rate and albumin mRNA expression were assayed daily. HAM alone or HAM plus hepatocytes (cultured for 3 days) were implanted in a subcutaneous pocket of the dorsal region of Gunn rats. No immunosuppression therapy was used. Blood samples were collected weekly and rats were sacrificed 10 weeks after surgery. Hepatocytes cultured on HAM displayed a higher proliferation rate than those cultured on plastic, and albumin mRNA expression was detected in hepatocytes seeded on HAM, but not on plastic. Serum bilirubin concentrations did not differ from baseline values in both the sham-operated control and HAM transplanted rats. On the contrary, in rats transplanted with HAM plus hepatocytes, circulating bilirubin levels decreased from week 4-7, and then plateaued until week 10. Histology did not evidence signs of rejection, but only a mild degree of inflammation around the implanted patches. It is concluded that hepatocytes seeded on HAM and transplanted into Gunn rats are able to metabolize bilirubin for at least two months, without signs of rejection even in the absence of immunosuppressive therapy.

Animals↗
PubMed2005

Inhibition of leukocyte elastase, polymorphonuclear chemoinvasion, and inflammation-triggered pulmonary fibrosis by a 4-alkyliden-beta-lactam with a galloyl moiety.

beta-Lactams, a well known class of antibiotics, have been investigated as inhibitors of the disruptive protease released by inflammatory cells, leukocyte elastase (LE). We have synthesized a new beta-lactam with an N-linked galloyl moiety, the latter identified as strategic in conferring anti-LE properties to some flavonols. This N-galloyl-derivative beta-lactam inhibits the LE activity with a K(i) of 0.7 microM, whereas it exerts weak activity against cathepsin G and protease-3 (IC(50) > 100 microM), and matrix metalloproteinase (MMP)-2 and MMP-9. Without affecting chemotactic response and viability of polymorphonuclear (PMN) leukocytes, the compound efficiently restrains their chemoinvasion (IC(50) of 1-2 microM) blocking the LE-triggered activation of pro-MMP-9, instrumental to extravasation. Daily i.p. injection of compound enhances resolution in a pulmonary inflammation model, significantly reducing consequent fibrosis. These results indicate that the new beta-lactam is a potent anti-inflammatory compound with therapeutic potential.

Animals↗
PubMed2005

Marked alveolar apoptosis/proliferation imbalance in end-stage emphysema.

BACKGROUND: Apoptosis has recently been proposed to contribute to the pathogenesis of emphysema. METHODS: In order to establish if cell fate plays a role even in end-stage disease we studied 16 lungs (9 smoking-associated and 7 alpha1antitrypsin (AAT)-deficiency emphysema) from patients who had undergone lung transplantations. Six unused donor lungs served as controls. Apoptosis was evaluated by TUNEL analysis, single-stranded DNA laddering, electron microscopy and cell proliferation by an immunohistochemical method (MIB1). The role of the transforming growth factor (TGF)-beta1 pathway was also investigated and correlated with epithelial cell turnover and with the severity of inflammatory cell infiltrate. RESULTS: The apoptotic index (AI) was significantly higher in emphysematous lungs compared to the control group (p < or = 0.01), particularly if only lungs with AAT-deficiency emphysema were considered (p < or = 0.01 vs p = 0.09). The proliferation index was similar in patients and controls (1.9 +/- 2.2 vs 1.7 +/- 1.1). An increased number of T lymphocytes was observed in AAT-deficiency lungs than smoking-related cases (p < or = 0.05). TGF-beta1 expression in the alveolar wall was higher in patients with smoking-associated emphysema than in cases with AAT-deficiency emphysema (p < or = 0.05). A positive correlation between TGF-betaRII and AI was observed only in the control group (p < or = 0.005, r2 = 0.8). A negative correlation was found between the TGF-beta pathway (particularly TGF-betaRII) and T lymphocytes infiltrate in smoking-related cases (p < or = 0.05, r2 = 0.99) CONCLUSION: Our findings suggest that apoptosis of alveolar epithelial cells plays an important role even in end-stage emphysema particularly in AAT-deficiency disease. The TGFbeta-1 pathway does not seem to directly influence epithelial turnover in end-stage disease. Inflammatory cytokine different from TGF-beta1 may differently orchestrate cell fate in AAT and smoking-related emphysema types.

Apoptosis↗
PubMed2005

Idiopathic interstitial pneumonias: Primum movens: epithelial, endothelial or whatever.

The pathogenesis of idiopathic interstitial pneumonias (IIPs), particularly of idiopathic pulmonary fibrosis (IPF), is still unknown and the precise nature of the primum movens is strongly debated. Epithelial cells can be the first target of various environmental toxic agents. Both types of pneumocytes may be injured. Type I pneumocyte loss, however, is most conspicuous in fibroblastic foci, the principal sites where irreversible fibrogenesis starts. Epithelial regeneration is highly disturbed: cuboidal and bronchial cells are mainly involved in alveolar repair. These cells, unable to accomplish important functions of normal pneumocytes, secrete various factors inducing migration and proliferation of fibroblasts responsible for progressive extracellular matrix accumulation and lung remodelling. Endothelial cells may also be considered the major players in the initiation of fibrogenic events. Microvascular injury has been largely demonstrated as an early event in IPF lungs. Thrombin as well as other coagulation products has many biological effects such as the activation of different profibrotic factors, which in addition to other fibrogenetic molecules released by stimulated endothelium, are responsible for migration and proliferation of fibroblasts. The old pathogenesis of IPF: chronic inflammation can now be considered the principal event in other non IPF-IIPs. Among inflammatory cells, different cell types have been extensively suggested to play a key role in the pathogenesis of pulmonary fibrosis: granulocytes and eosinophils or mast cells. More recently novel mechanisms underlying the pathogenesis of pulmonary fibrosis have been proposed: bone marrow-derived stem cells may play a crucial role in the fibroproliferative response as well as in epithelial regeneration.

Animals↗
PubMed2003

Parenchymal transforming growth factor beta-1: its type II receptor and Smad signaling pathway correlate with inflammation and fibrosis in chronic liver disease of viral etiology.

BACKGROUND AND AIMS: Transforming growth factor-beta (TGF-beta) system is involved in the control of cell growth and extracellular matrix formation. Previous studies in patients with chronic liver disease have shown that increased TGF-beta expression significantly correlates with the degree of hepatic fibrosis. The aim of our study was to define TGF-beta system expression in hepatic parenchymal cells and its significance in patients with differing extents of chronic liver disease of viral etiology. METHODS: Expression of TGF-beta 1, TGF-beta 1 type II receptor (TGF-beta RII) and the Smad signaling pathway was evaluated in consecutive liver sections of 77 patients with chronic liver disease (65 HCV positive and 12 HBV positive). Results were correlated with histological scores and apoptotic activity. RESULTS: TGF-beta 1 was demonstrated in the liver of 30/56 (53.6%) patients with chronic hepatitis and 20/21 (95%) patients with cirrhosis, but in none of the 20 normal livers. Positive cytokine reaction was seen both in stromal cells and hepatocytes. Expression of TGF-beta RII and Smad proteins showed a distribution pattern similar to that of TGF-beta, with a direct correlation in terms of immunoreactivity extent. A significant correlation was found between parenchymal expression of TGF-beta system and inflammatory and fibrosis scores. No correlation was found with apoptotic index and other morphological, clinical or virological parameters. CONCLUSIONS: The TGF-beta system is up-regulated at the ligand, receptor and signaling level in the liver of patients with more active disease. The strong expression of TGF-beta and the Smad pathway in parenchymal cells suggests that hepatocytes, in addition to mesenchymal cells, may play an important role in the progression of liver disease.

Adolescent↗
PubMed2002

Recurrence of idiopathic pulmonary hemosiderosis in a young adult patient after bilateral single-lung transplantation.

BACKGROUND: Idiopathic pulmonary hemosiderosis (IPH) is a rare disease of unknown etiology characterized by hemoptysis, diffuse pulmonary infiltration, and anemia. Diagnosis requires a detailed clinical history and transbronchial lung biopsy (TLB). METHODS AND RESULTS: A 19-year-old man developed progressive dyspnea, hemoptysis, and anemia. The chest x-rays showed bilateral opacities. IPH was diagnosed on the basis of clinical findings and TLB. The patient was treated with corticosteroidal therapy. His respiratory function worsened, and he underwent lung transplantation in 1997. The pathological examination on native lungs confirmed the previous histologic diagnosis. In 2000, the patient again developed hemoptysis, fever, and hypoxemia. A recurrence of the disease was established by TLB. CONCLUSIONS: This is the first report of recurring IPH. The possibility of recurrent IPH raises the question whether these patients should be disqualified from lung transplantation. This question is unanswerable because incidence of recurrence, time course, and impact on the graft function are presently unknown and unpredictable.

Adult↗