Luigi Bolondi
University of Bologna
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Featured researches published by Luigi Bolondi.
The New England Journal of Medicine | 2008
Josep M. Llovet; Sergio Ricci; Vincenzo Mazzaferro; Philip Hilgard; Edward Gane; Jean Frédéric Blanc; André Cosme de Oliveira; Armando Santoro; Jean Luc Raoul; Alejandro Forner; Myron Schwartz; Camillo Porta; Stefan Zeuzem; Luigi Bolondi; Tim F. Greten; Peter R. Galle; Jean Francois Seitz; Ivan Borbath; Dieter Häussinger; Tom Giannaris; M. Shan; M. Moscovici; Dimitris Voliotis; Jordi Bruix
BACKGROUND No effective systemic therapy exists for patients with advanced hepatocellular carcinoma. A preliminary study suggested that sorafenib, an oral multikinase inhibitor of the vascular endothelial growth factor receptor, the platelet-derived growth factor receptor, and Raf may be effective in hepatocellular carcinoma. METHODS In this multicenter, phase 3, double-blind, placebo-controlled trial, we randomly assigned 602 patients with advanced hepatocellular carcinoma who had not received previous systemic treatment to receive either sorafenib (at a dose of 400 mg twice daily) or placebo. Primary outcomes were overall survival and the time to symptomatic progression. Secondary outcomes included the time to radiologic progression and safety. RESULTS At the second planned interim analysis, 321 deaths had occurred, and the study was stopped. Median overall survival was 10.7 months in the sorafenib group and 7.9 months in the placebo group (hazard ratio in the sorafenib group, 0.69; 95% confidence interval, 0.55 to 0.87; P<0.001). There was no significant difference between the two groups in the median time to symptomatic progression (4.1 months vs. 4.9 months, respectively, P=0.77). The median time to radiologic progression was 5.5 months in the sorafenib group and 2.8 months in the placebo group (P<0.001). Seven patients in the sorafenib group (2%) and two patients in the placebo group (1%) had a partial response; no patients had a complete response. Diarrhea, weight loss, hand-foot skin reaction, and hypophosphatemia were more frequent in the sorafenib group. CONCLUSIONS In patients with advanced hepatocellular carcinoma, median survival and the time to radiologic progression were nearly 3 months longer for patients treated with sorafenib than for those given placebo. (ClinicalTrials.gov number, NCT00105443.)
Cancer Research | 2007
Laura Gramantieri; Manuela Ferracin; Francesca Fornari; Angelo Veronese; Silvia Sabbioni; Chang Gong Liu; George A. Calin; Catia Giovannini; Eros Ferrazzi; Gian Luca Grazi; Carlo M. Croce; Luigi Bolondi; Massimo Negrini
We investigated the role of microRNAs (miRNAs) in the pathogenesis of human hepatocellular carcinoma (HCC). A genome-wide miRNA microarray was used to identify differentially expressed miRNAs in HCCs arisen on cirrhotic livers. Thirty-five miRNAs were identified. Several of these miRNAs were previously found deregulated in other human cancers, such as members of the let-7 family, mir-221, and mir-145. In addition, the hepato-specific miR-122a was found down-regulated in approximately 70% of HCCs and in all HCC-derived cell lines. Microarray data for let-7a, mir-221, and mir-122a were validated by Northern blot and real-time PCR analysis. Understanding the contribution of deregulated miRNAs to cancer requires the identification of gene targets. Here, we show that miR-122a can modulate cyclin G1 expression in HCC-derived cell lines and an inverse correlation between miR-122a and cyclin G1 expression exists in primary liver carcinomas. These results indicate that cyclin G1 is a target of miR-122a and expand our knowledge of the molecular alterations involved in HCC pathogenesis and of the role of miRNAs in human cancer.
Gut | 2001
Luigi Bolondi; Soccorsa Sofia; Sebastiano Siringo; Stefano Gaiani; A.M. Casali; Gianni Zironi; Fabio Piscaglia; Laura Gramantieri; M Zanetti; Morris Sherman
BACKGROUND Hepatocellular carcinoma (HCC) is a major cause of death in cirrhotic patients. This neoplasm is associated with liver cirrhosis (LC) in more than 90% of cases. Early diagnosis and treatment of HCC are expected to improve survival of patients. AIMS To assess the cost effectiveness of a surveillance programme of patients with LC for the early diagnosis and treatment of HCC. PATIENTS A cohort of 313 Italian patients with LC were enrolled in the surveillance programme between March 1989 and November 1991. In the same period, 104 consecutive patients with incidentally detected HCC were referred to our centre and served as a control group. METHODS Surveillance was based on ultrasonography (US) and α fetoprotein (AFP) determinations repeated at six month intervals. Risk factors for HCC were assessed by multivariate analysis (Cox model). Outcome measures analysed were: (1) number and size of tumours; (2) eligibility for treatment; and (3) survival of patients. Economic issues were: (1) overall cost of surveillance programme; (2) cost per treatable HCC; and (3) cost per year of life saved (if any). Costs were assessed according to charges for procedures at our university hospital. RESULTS Surveillance lasted a mean of 56 (31) months (range 6–100). During the follow up, 61 patients (19.5%) developed HCC (unifocal at US in 49 cases), with an incidence of 4.1% per year of follow up. AFP, Child-Pugh classes B and C, and male sex were detected as independent risk factors for developing HCC. Only 42 (68.9%) of 61 liver tumours were treated by surgical resection, orthotopic liver transplantation, or local therapy. The cumulative survival rate of the 61 patients with liver tumours detected in the surveillance programme was significantly longer than that of controls (p=0.02) and multivariate analysis showed an association between surveillance and survival. The overall cost of the surveillance programme was US
Oncogene | 2008
Francesca Fornari; Laura Gramantieri; Manuela Ferracin; Angelo Veronese; Silvia Sabbioni; Ga Calin; Gian Luca Grazi; Catia Giovannini; Cm Croce; Luigi Bolondi; Massimo Negrini
753 226, the cost per treatable HCC was US
Journal of Hepatology | 2012
Jordi Bruix; Jean Luc Raoul; Morris Sherman; Vincenzo Mazzaferro; Luigi Bolondi; A. Craxì; Peter R. Galle; Armando Santoro; Michel Beaugrand; A. Sangiovanni; Camillo Porta; Guido Gerken; Jorge A. Marrero; Andrea Nadel; Michael Shan; M. Moscovici; Dimitris Voliotis; Josep M. Llovet
17 934, and the cost for year of life saved was US
Cancer | 1992
Tito Livraghi; Luigi Bolondi; Sergio Lazzaroni; Giuseppe Marin; Alberto Morabito; Gian Ludovico Rapaccini; Andrea Salmi; Guido Torzilli
112 993. CONCLUSION Our surveillance policy of patients with LC requires a large number of resources and offers little benefit in terms of patient survival. The decision whether to adopt a surveillance policy towards HCC should rely on the prevalence of the disease in the population and on the resources of a particular country.
Gastroenterology | 1985
Luigi Bolondi; Mauro Bortolotti; Vittorio Santi; Tiziana Calletti; Stefano Gaiani; Labò G
The identification of target mRNAs is a key step for assessing the role of aberrantly expressed microRNAs in human cancer. MiR-221 is upregulated in human hepatocellular carcinoma (HCC) as well as in other malignancies. One proven target of miR-221 is CDKN1B/p27, whose downregulation affects HCC prognosis. Here, we proved that the cyclin-dependent kinase inhibitor (CDKI) CDKN1C/p57 is also a direct target of miR-221. Indeed, downregulation of both CDKN1B/p27 and CDKN1C/p57 occurs in response to miR-221 transfection into HCC-derived cells and a significant upregulation of both CDKN1B/p27 and CDKN1C/p57 occurs in response to antimiR-221 transfection. A direct interaction of miR-221 with a target site on the 3′ UTR of CDKN1C/p57 mRNA was also demonstrated. By controlling these two CDKIs, upregulation of miR-221 can promote growth of HCC cells by increasing the number of cells in S-phase. To assess the relevance of these studies in primary tumors, matched HCC and cirrhosis samples were assayed for miR-221, for CDKN1B/p27 and CDKN1C/p57 expression. MiR-221 was upregulated in 71% of HCCs, whereas CDKN1B/p27 and CDKN1C/p57 proteins were downregulated in 77% of cases. A significant inverse correlation between miR-221 and both CDKN1B/p27 and CDKN1C/p57 was found in HCCs. In conclusion, we suggest that miR-221 has an oncogenic function in hepatocarcinogenesis by targeting CDKN1B/p27 and CDKN1C/p57, hence promoting proliferation by controlling cell-cycle inhibitors. These findings establish a basis toward the development of therapeutic strategies aimed at blocking miR-221 in HCC.
Cancer Treatment Reviews | 2011
Jean Luc Raoul; Bruno Sangro; Alejandro Forner; Vincenzo Mazzaferro; Fabio Piscaglia; Luigi Bolondi; Riccardo Lencioni
BACKGROUND & AIMS The Sorafenib Hepatocellular Carcinoma (HCC) Assessment Randomized Protocol (SHARP) trial demonstrated that sorafenib improves overall survival and is safe for patients with advanced HCC. In this trial, 602 patients with well-preserved liver function (>95% Child-Pugh A) were randomized to receive either sorafenib 400mg or matching placebo orally b.i.d. on a continuous basis. Because HCC is a heterogeneous disease, baseline patient characteristics may affect individual responses to treatment. In a comprehensive series of exploratory subgroup analyses, data from the SHARP trial were analyzed to discern if baseline patient characteristics influenced the efficacy and safety of sorafenib. METHODS Five subgroup domains were assessed: disease etiology, tumor burden, performance status, tumor stage, and prior therapy. Overall survival (OS), time to progression (TTP), disease control rate (DCR), and safety were assessed for subgroups within each domain. RESULTS Subgroup analyses showed that sorafenib consistently improved median OS compared with placebo, as reflected by hazard ratios (HRs) of 0.50-0.85, similar to the complete cohort (HR=0.69). Sorafenib also consistently improved median TTP (HR, 0.40-0.64), except in HBV-positive patients (HR, 1.03), and DCR. Results are limited by small patient numbers in some subsets. The most common grade 3/4 adverse events included diarrhea, hand-foot skin reaction, and fatigue; the incidence of which did not differ appreciably among subgroups. CONCLUSIONS These exploratory subgroup analyses showed that sorafenib consistently improved median OS and DCR compared with placebo in patients with advanced HCC, irrespective of disease etiology, baseline tumor burden, performance status, tumor stage, and prior therapy.
Cancer Research | 2009
Francesca Fornari; Laura Gramantieri; Catia Giovannini; Angelo Veronese; Manuela Ferracin; Silvia Sabbioni; George A. Calin; Gian Luca Grazi; Carlo M. Croce; Simona Tavolari; Pasquale Chieco; Massimo Negrini; Luigi Bolondi
In 207 cirrhotic patient carriers of hepatocellular carcinoma (HCC), percutaneous ethanol injection (PEI) was administered with ultrasound guidance. The patients were classified as Childs Class A, 136; B, 54; and C, 17. Their mean age was 63.5 years, and the male‐female ratio was 3.5:1. There was a single HCC less than 5 cm in diameter in 162 patients; 45 had more than one HCC. The follow‐up ranged from 5 to 71 months (mean, 25 months). No noteworthy complications occurred during or after 2485 treatments. The 1‐year, 2‐year, and 3‐year survival percentages (by the Kaplan‐Meier method) for the patients with one HCC were 90%, 80%, and 63%, respectively. The corresponding percentages by Childs class were 97%, 92%, and 76% for Class A; 88%, 68%, and 42% for B; and 40%, 0%, and 0% for C. The 1‐year, 2‐year, and 3‐year survival rates for patients with more than one HCC were 90%, 67%, and 31%, respectively. These results were similar to those found by others and showed that PEI was a safe, reproducible, easy‐to‐do, and low‐cost therapeutic technique. In terms of survival, these PEI results were better than the published results of no treatment and equivalent to those of surgery. In uncontrolled series, bias can play an important role. Therefore, additional trials would be useful. Cancer 1992; 69: 925–929.
Cancer Research | 2010
Francesca Fornari; Maddalena Milazzo; Pasquale Chieco; Massimo Negrini; George A. Calin; Gian Luca Grazi; Daniela Pollutri; Carlo M. Croce; Luigi Bolondi; Laura Gramantieri
This paper describes an ultrasound method of assessing gastric emptying time based on measurements of the gastric antrum, which is visible in almost all subjects before and after meals. A total of 54 subjects were examined including 18 normal subjects and 36 subjects with idiopathic functional dyspepsia. The emptying time was determined in all subjects by measuring the changes in the cross-sectional area of the gastric antrum. In a subgroup of 34 subjects the volume of the whole antropyloric region was also considered. Measurements were taken by the same observer after fasting and at regular 30-min intervals after a standard 800-cal meal. Final emptying time (calculated in relation to the start of the meal) was considered to be the time at which the antral area or volume returned to basal value. Final emptying time (mean +/- SD) was 248 +/- 39 min in normal subjects and 359 +/- 64 min in patients with functional dyspepsia (p less than 0.001). A significantly higher degree of dilatation of the gastric antrum was found in dyspeptic patients than in control subjects. Barium x-ray of the stomach in 19 subjects always confirmed the ultrasound finding on the presence or absence of contents within the stomach. We conclude that this kind of ultrasound study of the antropyloric region allows accurate determination of total gastric emptying time.