Search Results

You are looking at 1 - 3 of 3 items for

  • Author: E Puxeddu x
  • Refine by access: All content x
Clear All Modify Search
E Puxeddu
Search for other papers by E Puxeddu in
Google Scholar
PubMed
Close
,
J A Knauf
Search for other papers by J A Knauf in
Google Scholar
PubMed
Close
,
M A Sartor
Search for other papers by M A Sartor in
Google Scholar
PubMed
Close
,
N Mitsutake
Search for other papers by N Mitsutake in
Google Scholar
PubMed
Close
,
E P Smith
Search for other papers by E P Smith in
Google Scholar
PubMed
Close
,
M Medvedovic
Search for other papers by M Medvedovic in
Google Scholar
PubMed
Close
,
C R Tomlinson
Search for other papers by C R Tomlinson in
Google Scholar
PubMed
Close
,
S Moretti
Search for other papers by S Moretti in
Google Scholar
PubMed
Close
, and
J A Fagin
Search for other papers by J A Fagin in
Google Scholar
PubMed
Close

RET/PTC rearrangements represent key genetic events involved in papillary thyroid carcinoma (PTC) initiation. The aim of the present study was to identify the early changes in gene expression induced by RET/PTC in thyroid cells. For this purpose, microarray analysis was conducted on PCCL3 cells conditionally expressing the RET/PTC3 oncogene. Gene expression profiling 48 h after activation of RET/PTC3 identified a statistically significant modification of expression of 270 genes. Quantitative PCR confirmation of 20 of these demonstrated 90% accuracy of the microarray. Functional clustering of genes with greater than or less than 1.75-fold expression change (86 genes) revealed RET/PTC3-induced regulation of genes with key functions in apoptosis (Ripk3, Tdga), cell–cell signaling (Cdh6, Fn1), cell cycle (Il24), immune and inflammation response (Cxcl10, Scya2, Il6, Gbp2, Oas1, Tap1, RT1Aw2, C2ta, Irf1, Lmp2, Psme2, Prkr), metabolism (Aldob, Ptges, Nd2, Gss, Gstt1), signal transduction (Socs3, Nf1, Jak2, Cpg21, Dusp6, Socs1, Stat1, Stat3, Cish) and transcription (Nr4a1, Junb, Hfh1, Runx1, Foxe1). Genes coding for proteins involved in the immune response and in intracellular signal transduction pathways activated by cytokines and chemokines were strongly represented, indicating a critical role of RET/PTC3 in the early modulation of the immune response.

Free access
M Celano
Search for other papers by M Celano in
Google Scholar
PubMed
Close
,
S Schenone Department of Pharmacobiological Sciences, Department of Pharmaceutical Sciences, Pharmaco-Biological Department, Department of Internal Medicine, Department of Clinical Sciences, Pharmaco-Chemical-Technological Department, University of Catanzaro ‘Magna Græcia’, Campus Universitario, loc. Germaneto, Viale Europa, 88100 Catanzaro, Italy

Search for other papers by S Schenone in
Google Scholar
PubMed
Close
,
D Cosco
Search for other papers by D Cosco in
Google Scholar
PubMed
Close
,
M Navarra Department of Pharmacobiological Sciences, Department of Pharmaceutical Sciences, Pharmaco-Biological Department, Department of Internal Medicine, Department of Clinical Sciences, Pharmaco-Chemical-Technological Department, University of Catanzaro ‘Magna Græcia’, Campus Universitario, loc. Germaneto, Viale Europa, 88100 Catanzaro, Italy

Search for other papers by M Navarra in
Google Scholar
PubMed
Close
,
E Puxeddu Department of Pharmacobiological Sciences, Department of Pharmaceutical Sciences, Pharmaco-Biological Department, Department of Internal Medicine, Department of Clinical Sciences, Pharmaco-Chemical-Technological Department, University of Catanzaro ‘Magna Græcia’, Campus Universitario, loc. Germaneto, Viale Europa, 88100 Catanzaro, Italy

Search for other papers by E Puxeddu in
Google Scholar
PubMed
Close
,
L Racanicchi Department of Pharmacobiological Sciences, Department of Pharmaceutical Sciences, Pharmaco-Biological Department, Department of Internal Medicine, Department of Clinical Sciences, Pharmaco-Chemical-Technological Department, University of Catanzaro ‘Magna Græcia’, Campus Universitario, loc. Germaneto, Viale Europa, 88100 Catanzaro, Italy

Search for other papers by L Racanicchi in
Google Scholar
PubMed
Close
,
C Brullo Department of Pharmacobiological Sciences, Department of Pharmaceutical Sciences, Pharmaco-Biological Department, Department of Internal Medicine, Department of Clinical Sciences, Pharmaco-Chemical-Technological Department, University of Catanzaro ‘Magna Græcia’, Campus Universitario, loc. Germaneto, Viale Europa, 88100 Catanzaro, Italy

Search for other papers by C Brullo in
Google Scholar
PubMed
Close
,
E Varano
Search for other papers by E Varano in
Google Scholar
PubMed
Close
,
S Alcaro
Search for other papers by S Alcaro in
Google Scholar
PubMed
Close
,
E Ferretti Department of Pharmacobiological Sciences, Department of Pharmaceutical Sciences, Pharmaco-Biological Department, Department of Internal Medicine, Department of Clinical Sciences, Pharmaco-Chemical-Technological Department, University of Catanzaro ‘Magna Græcia’, Campus Universitario, loc. Germaneto, Viale Europa, 88100 Catanzaro, Italy

Search for other papers by E Ferretti in
Google Scholar
PubMed
Close
,
G Botta Department of Pharmacobiological Sciences, Department of Pharmaceutical Sciences, Pharmaco-Biological Department, Department of Internal Medicine, Department of Clinical Sciences, Pharmaco-Chemical-Technological Department, University of Catanzaro ‘Magna Græcia’, Campus Universitario, loc. Germaneto, Viale Europa, 88100 Catanzaro, Italy

Search for other papers by G Botta in
Google Scholar
PubMed
Close
,
S Filetti Department of Pharmacobiological Sciences, Department of Pharmaceutical Sciences, Pharmaco-Biological Department, Department of Internal Medicine, Department of Clinical Sciences, Pharmaco-Chemical-Technological Department, University of Catanzaro ‘Magna Græcia’, Campus Universitario, loc. Germaneto, Viale Europa, 88100 Catanzaro, Italy

Search for other papers by S Filetti in
Google Scholar
PubMed
Close
,
M Fresta
Search for other papers by M Fresta in
Google Scholar
PubMed
Close
,
M Botta Department of Pharmacobiological Sciences, Department of Pharmaceutical Sciences, Pharmaco-Biological Department, Department of Internal Medicine, Department of Clinical Sciences, Pharmaco-Chemical-Technological Department, University of Catanzaro ‘Magna Græcia’, Campus Universitario, loc. Germaneto, Viale Europa, 88100 Catanzaro, Italy

Search for other papers by M Botta in
Google Scholar
PubMed
Close
, and
D Russo
Search for other papers by D Russo in
Google Scholar
PubMed
Close

In this study, we evaluated the activity of two novel pyrazolopyrimidine derivatives (Si 34 and Si 35) against ARO cells, a human anaplastic thyroid cancer cell line. ARO cells exposed to different concentrations of the drugs showed a reduced growth rate and an increase of mortality. After 72 h incubation, doses of 5 and 10 μM Si 34 determined a decrease of cell counts by ∼25% and ∼75% compared with those of control cells respectively. Similar findings were observed using Si 35. Treatment with both Si 34 and Si 35 at 10 μM increased cell mortality also (∼29% and ∼18% respectively). At these concentrations, a decrease in cyclin D1 levels was observed. To improve the biopharmaceutical properties, a liposome formulation was prepared. When entrapped in unilamellar liposomes, Si 34 exerted its cytotoxic effects even at lower doses (maximal inhibition at 5 μM) and after shorter incubation time (48 h) either in ARO or other thyroid cancer cell lines. The effects were associated with weak apoptotic death. Inhibition of epidermal growth factor-stimulated src and ERK phosphorylation, as well as reduction of migration properties of ARO cells was also observed. Moreover, the growth of tumor xenografts induced in severe combined immunodeficiency (SCID) mice was inhibited by i.v. administration of 25–50 mg/kg of the drug liposomal formulation. In conclusion, the liposomal preparation of this novel pyrazolopyrimidine derivative appears to be a promising tool for the treatment of anaplasic thyroid cancer.

Free access
L Fugazzola
Search for other papers by L Fugazzola in
Google Scholar
PubMed
Close
,
E Puxeddu
Search for other papers by E Puxeddu in
Google Scholar
PubMed
Close
,
N Avenia
Search for other papers by N Avenia in
Google Scholar
PubMed
Close
,
C Romei
Search for other papers by C Romei in
Google Scholar
PubMed
Close
,
V Cirello
Search for other papers by V Cirello in
Google Scholar
PubMed
Close
,
A Cavaliere
Search for other papers by A Cavaliere in
Google Scholar
PubMed
Close
,
P Faviana
Search for other papers by P Faviana in
Google Scholar
PubMed
Close
,
D Mannavola
Search for other papers by D Mannavola in
Google Scholar
PubMed
Close
,
S Moretti
Search for other papers by S Moretti in
Google Scholar
PubMed
Close
,
S Rossi
Search for other papers by S Rossi in
Google Scholar
PubMed
Close
,
M Sculli
Search for other papers by M Sculli in
Google Scholar
PubMed
Close
,
V Bottici
Search for other papers by V Bottici in
Google Scholar
PubMed
Close
,
P Beck-Peccoz
Search for other papers by P Beck-Peccoz in
Google Scholar
PubMed
Close
,
F Pacini
Search for other papers by F Pacini in
Google Scholar
PubMed
Close
,
A Pinchera
Search for other papers by A Pinchera in
Google Scholar
PubMed
Close
,
F Santeusanio
Search for other papers by F Santeusanio in
Google Scholar
PubMed
Close
, and
R Elisei
Search for other papers by R Elisei in
Google Scholar
PubMed
Close

Recently, a somatic point mutation of the B-RAF gene (V600E) has been identified as the most common genetic event in papillary thyroid carcinoma (PTC), with a prevalence variable among different series. Since discordant data on the clinico-pathologic features of B-RAF mutated PTC are present in the literature, the aim of the present co-operative study was to establish the prevalence of this genetic alteration and to perform a genotype–phenotype correlation in a large cohort of patients with PTC. To this purpose, a series of 260 sporadic PTCs with different histological variants were included in the study. The mutational analysis of the B-RAF gene was performed either by RT-PCR followed by single-stranded conformational polymorphism or by PCR and direct sequencing. Statistical analyses were obtained by means of χ2/Fisher’s exact test and t-test. Overall, a heterozygous T > A transversion at nucleotide 1799 (V600E) was found in 99 out of 260 PTCs (38%). According to the histological type of the tumor, the B-RAF V600E mutation was present in 48.3% of cases of classic PTCs (85 out of 176), in 17.6% (nine out of 51) of follicular variants of PTCs, in 21.7% (five out of 23) in other PTC variants and in none of the ten poorly differentiated tumors. B-RAF V600E was significantly associated with the classic variant of PTC (P = 0.0001) and with an older age at diagnosis (P = 0.01). No statistically significant correlation was found among the presence of B-RAF V600E and gender, tumor node metastasis (TNM), multicentricity of the tumor, stage at diagnosis and outcome. In conclusion, the present study reports the prevalence of B-RAF V600E (38%) in the largest series of sporadic PTCs, including 260 cases from three different Italian referring centers. This prevalence is similar to that calculated by pooling together all data previously reported, 39.6% (759 out of 1914 cases), thus indicating that the prevalence of this genetic event lies around 38–40%. Furthermore, B-RAF V600E was confirmed to be associated with the papillary growth pattern, but not with poorer differentiated PTC variants. A significant association of B-RAF mutation was also found with an older age at diagnosis, the mutation being very rare in childhood and adolescent PTCs. Finally, no correlation was found with a poorer prognosis and a worse outcome after a median follow-up of 72 months.

Free access