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Biomedical subjects

Carlo Ferretti

Publications and source records attributed to Carlo Ferretti.

6 recordsLinked to original sources

Peroxisome proliferator-activated receptor ligands affect growth-related gene expression in human leukemic cells.

Peroxisome proliferator-activated receptors (PPARs) are ligand-activated nuclear receptors. Three subtypes of PPARs (alpha, beta, and gamma) have been identified in different tissues. PPAR alpha and PPAR gamma ligands inhibit cell proliferation and induce differentiation in several human cell models. We demonstrated that both PPAR alpha (clofibrate and ciprofibrate) and PPAR gamma ligands (troglitazone and 15 deoxy-prostaglandin J2, 15d-PGJ2) inhibited growth, induced the onset of monocytic-like differentiation, and increased the proportion of G0/G1 cells in the HL-60 leukemic cell line. Moreover, 3 days after the treatment with 2.5 microM 15d-PGJ2, an increase in sub-G0/G1 population occurred, compatible with an induction of programmed cell death. To clarify the mechanisms involved in HL-60 growth inhibition due to the effects of PPAR ligands, we investigated their action on the expression of some genes involved in the control of cell proliferation, differentiation, and cell cycle progression such as c-myc, c-myb, and cyclin D1 and D2. Clofibrate (50 microM), ciprofibrate (50 microM), and 15d-PGJ2 (2.5 microM) inhibited c-myb and cyclin D2 expression, whereas they did not affect c-myc and cyclin D1 expression. Only troglitazone (5 microM) decreased c-myc mRNA and protein levels, besides decreasing c-myb and cyclin D2. The down-regulations of c-myb and cyclin D2 expression represent the first evidence of the inhibitory effect exerted by PPAR ligands on these genes. Moreover, the inhibition of c-myc expression by troglitazone may depend on a PPAR-independent mechanism.

Antineoplastic Agents↗

Synergistic effect of 4-hydroxynonenal and PPAR ligands in controlling human leukemic cell growth and differentiation.

Peroxisome proliferator-activated receptors play an important role in the differentiation of different cell lines. In this study we demonstrate that PPAR-alpha ligands (clofibrate and ciprofibrate) and PPAR-gamma ligands (troglitazone and 15d-prostaglandin J2) inhibit growth and induce monocytic differentiation in HL-60 cells, whereas only PPAR-gamma ligands inhibit growth of U937 cells. Differentiation was demonstrated by the analysis of surface antigen expression CD11b and CD14, and by the characteristic morphological changes. PPAR-gamma ligands are more effective than PPAR-alpha ligands in the inhibition of cell growth and in the induction of differentiation. The physiological product of lipid peroxidation, 4-hydroxynonenal (HNE), which alone induces granulocytic-like differentiation of HL-60 cells, potentiates the monocytic differentiation induced by ciprofibrate, troglitazone, and 15d-prostaglandin J2. The same HNE treatment significantly inhibits U937 cell growth and potentiates the inhibition of cell growth in PPAR-gamma ligand-treated cells. However, HNE does not induce a significant number of CD14-positive U937 cells. HNE causes a great increase of PPAR-gamma expression in both HL-60 and U937 cells, whereas it does not modify the PPAR-alpha expression. This observation may account for the high synergistic effect displayed by HNE and PPAR-gamma ligands in the inhibition of cell growth and differentiation induction. These results represent the first evidence of the involvement of a product of lipid peroxidation in the modulation of PPAR ligand activity and suggest a relationship between HNE and PPAR ligand pathways in leukemic cell growth and differentiation.

Aldehydes↗

Mandibular, sagittal split osteotomies fixed with biodegradable or titanium screws: a prospective, comparative study of postoperative stability.

OBJECTIVE: Comparison of skeletal stability following bilateral sagittal split osteotomy (BSSO) advancement of the mandible fixed with titanium or biodegradable bicortical screws. STUDY DESIGN: Forty consecutive patients underwent mandibular advancement by means of BSSO performed with a standardized technique. In 20 patients rigid fixation was achieved by means of titanium bicortical screws; the other 20 patients were fixed with biodegradable copolymer screws made of poly-L-lactic acid (82%) and polyglycolic acid (18%). Lateral cephalograms were obtained 1 week preoperatively, 1 week postoperatively and after a minimum of 6 months postoperatively. Relevant skeletal points were traced and digitized to evaluate 2-dimensional skeletal change. Changes at each time point were analyzed and compared statistically. RESULTS: There was no statistically significant difference in long-term stability between the 2 groups. No clinical or radiographic evidence of wound healing problems were noted. CONCLUSION: Resorbable poly-L-lactic/polyglycolic acid copolymer bicortical screw fixation of a BSSO is a viable alternative to titanium screws for the fixation of advancement BSSO.

Absorbable Implants↗

Human segmental mandibular defects treated with naturally derived bone morphogenetic proteins.

Bone induction with extracted and partially purified, naturally derived bone morphogenetic proteins (BMPs) has been demonstrated repeatedly in heterotopic and orthotopic sites of non-human primates. This spawned the investigation of bone regeneration in mandibular defects of human patients with naturally derived BMPs and was compared with osteogenesis in patients treated with autologous bone grafts (ABGs). The osteogenic device (OD) was formulated as a combination of human demineralized bone matrix as delivery system reconstituted with naturally derived BMPs. BMPs were extracted from bovine bone with chaotropic agents and purified by sequential chromatography. Thirteen patients with segmental mandibular defects were enrolled in the trial, 6 of whom received the OD and 7 the ABGs. Defects were reconstructed with a preformed titanium mesh. The OD was combined with sterile saline and applied to the defects as a paste. Autologous bone from the iliac crest was prepared as a cortico-cancellous bone graft and loaded into the titanium mesh. Patients were followed-up clinically and radiographically at 1 and 6 weeks, 3, 6, and 12-month post-implantation. A trephine biopsy of the implants was performed at 3 months post-implantation and the specimens examined on serial undecalcified sections. Histological examination showed that the OD induced bone in 2 of 6 patients treated. Histological examination of successful implanted OD exhibited mineralized bone trabeculae with copious osteoid seams lined by contiguous osteoblasts. Bone deposition directly onto non-vital matrix provided unequivocal evidence of osteoinduction. Of the 7 patients grafted with ABGs, 5 had histological evidence of osteogenesis. Morphometric analysis of the histological sections showed that, when successful, OD-treated defects had highly active osteogenesis compared with ABGs. Whilst this trial provides valuable insights for the use of BMPs in mandibular reconstruction further work is required to produce an OD that will perform reliably in clinical contexts.

Adolescent↗