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Author

Luigi Bolondi

Other affiliations: University of Ferrara
Bio: Luigi Bolondi is an academic researcher from University of Bologna. The author has contributed to research in topics: Hepatocellular carcinoma & Cirrhosis. The author has an hindex of 81, co-authored 434 publications receiving 35056 citations. Previous affiliations of Luigi Bolondi include University of Ferrara.


Papers
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Journal ArticleDOI
TL;DR: 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.
Abstract: 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.

10,074 citations

Journal ArticleDOI
TL;DR: Treatment with cabozantinib resulted in longer overall survival and progression‐free survival than placebo among patients with previously treated advanced hepatocellular carcinoma, and the rate of high‐grade adverse events in the cabozaninib group was approximately twice that observed in the placebo group.
Abstract: Background Cabozantinib inhibits tyrosine kinases, including vascular endothelial growth factor receptors 1, 2, and 3, MET, and AXL, which are implicated in the progression of hepatocellul...

1,471 citations

Journal ArticleDOI
TL;DR: PEI proved safe, effective, and repeatable and had a low cost, probably because of a balancing between greater radicality of surgery and absence of early mortality and liver damage of PEI.
Abstract: PURPOSE: To define indications for percutaneous ethanol injection (PEI) in patients with hepatocellular carcinoma (HCC) and cirrhosis. MATERIALS AND METHODS: Survival rates were determined in 746 patients who had undergone PEI (567 men, 179 women; mean age, 64.3 years; mean follow-up, 36 months). RESULTS: In patients with Child A (n = 293), B (n = 149), or C (n = 20) cirrhosis and single HCCs 5 cm or smaller, the 3-5 year survival rate was 47%-79%, 29%-63%, and 0%-12%, respectively. In patients with Child A cirrhosis, it was 36%-68% for multiple HCCs (n = 121), 30%-53% for single HCCs larger than 5 cm (n = 28), and 0%-16% for advanced HCC (n = 16). Treatment was associated with a 1.7% rate of severe complications and a 0.1% mortality rate. CONCLUSION: PEI proved safe, effective, and repeatable and had a low cost. Survival after PEI was comparable to that after surgery, probably because of a balancing between greater radicality of surgery and absence of early mortality and liver damage of PEI.

903 citations

Journal ArticleDOI
TL;DR: Results indicate that cyclin G1 is a target of miR-122a and expand the knowledge of the molecular alterations involved in HCC pathogenesis and of the role of miRNAs in human cancer.
Abstract: 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.

803 citations

Journal ArticleDOI
TL;DR: In patients with HCV-related cirrhosis, DAA-induced resolution of HCV infection does not seem to reduce occurrence of HCC, and patients previously treated for HCC have still a high risk of tumour recurrence in the short term, despite DAA treatment.

769 citations


Cited by
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Journal ArticleDOI
TL;DR: The following Clinical Practice Guidelines will give up-to-date advice for the clinical management of patients with hepatocellular carcinoma, as well as providing an in-depth review of all the relevant data leading to the conclusions herein.

7,851 citations

Journal ArticleDOI
TL;DR: The American Association for the Study of Liver Diseases (AASLD) practice guidelines on the management of hepatocellular carcinoma (HCC) were updated in 2010 as discussed by the authors.

6,964 citations

Journal ArticleDOI
Donna M. Muzny1, Matthew N. Bainbridge1, Kyle Chang1, Huyen Dinh1  +317 moreInstitutions (24)
19 Jul 2012-Nature
TL;DR: Integrative analyses suggest new markers for aggressive colorectal carcinoma and an important role for MYC-directed transcriptional activation and repression.
Abstract: To characterize somatic alterations in colorectal carcinoma, we conducted a genome-scale analysis of 276 samples, analysing exome sequence, DNA copy number, promoter methylation and messenger RNA and microRNA expression. A subset of these samples (97) underwent low-depth-of-coverage whole-genome sequencing. In total, 16% of colorectal carcinomas were found to be hypermutated: three-quarters of these had the expected high microsatellite instability, usually with hypermethylation and MLH1 silencing, and one-quarter had somatic mismatch-repair gene and polymerase e (POLE) mutations. Excluding the hypermutated cancers, colon and rectum cancers were found to have considerably similar patterns of genomic alteration. Twenty-four genes were significantly mutated, and in addition to the expected APC, TP53, SMAD4, PIK3CA and KRAS mutations, we found frequent mutations in ARID1A, SOX9 and FAM123B. Recurrent copy-number alterations include potentially drug-targetable amplifications of ERBB2 and newly discovered amplification of IGF2. Recurrent chromosomal translocations include the fusion of NAV2 and WNT pathway member TCF7L1. Integrative analyses suggest new markers for aggressive colorectal carcinoma and an important role for MYC-directed transcriptional activation and repression.

6,883 citations

01 Jan 2010
TL;DR: Since the publication of the American Association for the Study of Liver Diseases (AASLD) practice guidelines on the management of hepatocellular carcinoma (HCC) in 2005, new information has emerged that requires that the guidelines be updated.
Abstract: Since the publication of the American Association for the Study of Liver Diseases (AASLD) practice guidelines on the management of hepatocellular carcinoma (HCC) in 2005, new information has emerged that requires that the guidelines be updated. The full version of the new guidelines is available on the AASLD Web site at http://www.aasld.org/practiceguidelines/ Documents/Bookmarked%20Practice%20Guidelines/ HCCUpdate2010.pdf. Here, we briefly describe only new or changed recommendations.

6,642 citations

Journal ArticleDOI
TL;DR: The prevention of Cirrhosis can prevent the development of HCC and progression from chronic HCV infection to advanced fibrosis or cirrhosis may be prevented in 40% of patients who are sustained responders to new antiviral strategies, such as pegylated interferon and ribavirin.

5,557 citations