Apoptosis promoted by up-regulation of TFPT (TCF3 fusion partner) appears p53 independent, cell type restricted and cell density influenced.

The TFPT/FB1 gene was identified because of its involvement in childhood pre-B acute lymphoblastic leukaemia (ALL). Although its specific function is still unclear, Tfpt has been implicated in cell proliferation and induction of programmed cell death (PCD). Given the critical role of PCD in leukemogenesis, we have investigated the responsiveness of different cell lines to TFPT over expression and the consequent induction of PCD by proliferation kinetic analysis, immunolocalization and TUNEL assay. We have also tested the involvement of factors implicated in cell cycle progression and apoptosis, i.e. caspases, p53, Cdc2. Our results indicate that over expression of TFPT promotes caspase 9-dependent apoptosis, nevertheless the apoptotic cascade is engaged only in culture conditions sustaining cell proliferation and different cell lines display differential responsiveness to TFPT induced apoptosis Although p53 is a main regulator of apoptosis in mammalian cells, the Tfpt induced apoptosis appears p53-independent. These results are discussed relatively to the role played by TFPT in leukemogenesis.

Early-stage hepatocellular carcinoma in patients with cirrhosis: long-term results of percutaneous image-guided radiofrequency ablation.

PURPOSE: To perform a prospective, intention-to-treat clinical trial to determine the long-term survival rates of patients with hepatic cirrhosis and early-stage hepatocellular carcinoma (HCC) in whom percutaneous image-guided radiofrequency (RF) ablation was used as the sole first-line anticancer treatment. MATERIALS AND METHODS: The study was performed with approval of the ethics committee, and written informed consent was obtained for all patients. From June 1, 1996, to January 1, 2003, 206 patients (143 men, 63 women; age range, 51-81 years; mean age, 67 years +/- 7) who were excluded from surgery and who had Child class A or B cirrhosis with either a single HCC less than or equal to 5 cm in diameter or multiple (as many as three) HCCs less than or equal to 3 cm in diameter each were enrolled. RF ablation was performed in 187 (91%) of 206 patients; 19 (9%) were excluded from RF treatment because of unfavorable tumor location. Follow-up ranged from 3 to 78 months (mean, 24 months +/- 21) and included measurement of alpha-fetoprotein level, ultrasonography at 3-month intervals, and spiral computed tomography at 6-month intervals. Patients were observed for recurrence of the treated tumor and for the emergence of new HCC tumors. Survival probabilities were estimated with the Kaplan-Meier method, and differences between survival curves were evaluated with the log-rank test. RESULTS: At the end of the study, 145 patients were alive, and 61 were dead. In the intention-to-treat analysis, overall survival rates were 97% at 1 year, 67% at 3 years, and 41% at 5 years. Median survival was 49 months. In the 187 patients treated with RF ablation, overall survival rates were 97% at 1 year, 71% at 3 years, and 48% at 5 years. Median survival was 57 months. The difference between the two survival curves was not statistically significant (P=.5094). Survival of patients treated with RF ablation was dependent on Child class (P=.0006) and tumor multiplicity (P=.0133). Patients who had Child class A cirrhosis with solitary HCC (n=116) had 1-, 3-, and 5-year survival rates of 100%, 89% and 61%; median survival was 65 months. The 1-, 3-, and 5-year recurrence rates were 14%, 49%, and 81% for the emergence of new tumors and 4%, 10%, and 10% for local tumor progression. CONCLUSION: RF ablation is an effective first-line treatment for cirrhotic patients with early-stage HCC who were excluded from surgery.

Radiofrequency ablation of lung malignancies: where do we stand?

Percutaneous radiofrequency (RF) ablation is a minimally invasive technique used to treat solid tumors. Because of its ability to produce large volumes of coagulation necrosis in a controlled fashion, this technique has gained acceptance as a viable therapeutic option for unresectable liver malignancies. Recently, investigation has been focused on the clinical application of RF ablation in the treatment of lung malignancies. In theory, lung tumors are well suited to RF ablation because the surrounding air in adjacent normal parenchyma provides an insulating effect, thus facilitating energy concentration within the tumor tissue. Experimental studies in rabbits have confirmed that lung RF ablation can be safely and effectively performed via a percutaneous, transthoracic approach, and have prompted the start of clinical investigation. Pilot clinical studies have shown that RF ablation enables successful treatment of relatively small lung malignancies with a high rate of complete response and acceptable morbidity, and have suggested that the technique could represent a viable alternate or complementary treatment method for patients with non-small cell lung cancer or lung metastases of favorable histotypes who are not candidates for surgical resection. This article gives an overview of lung RF ablation, discussing experimental animal findings, rationale for clinical application, technique and methodology, clinical results, and complications.