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Article: Liquid biopsy: New opportunities for precision medicine in hepatocellular carcinoma care.

Aquino, Inah Marie C / Pascut, Devis

2023 Volume 29, Issue 2, Page(s) 101176

Abstract: Liquid biopsy, specifically the analysis of circulating tumor DNA (ctDNA), offers a non-invasive approach for hepatocellular carcinoma (HCC) diagnosis and management. However, its implementation in the clinical setting is difficult due to challenges such ...

Abstract	Liquid biopsy, specifically the analysis of circulating tumor DNA (ctDNA), offers a non-invasive approach for hepatocellular carcinoma (HCC) diagnosis and management. However, its implementation in the clinical setting is difficult due to challenges such as low ctDNA yield and difficulty in understanding the mutation signals from background noise. This review highlights the crucial role of artificial intelligence (AI) in addressing these limitations and in improving discoveries in the field of liquid biopsy for HCC care. Combining AI with liquid biopsy data can offer a promising future for the discovery of novel biomarkers and an AI-powered clinical decision support system (CDSS) can turn liquid biopsy into an important tool for personalized management of HCC. Despite the current challenges, the integration of AI shows promise to significantly improve patient outcomes and revolutionize the field of oncology.
MeSH term(s)	Humans ; Carcinoma, Hepatocellular/diagnosis ; Carcinoma, Hepatocellular/genetics ; Carcinoma, Hepatocellular/therapy ; Liver Neoplasms/diagnosis ; Liver Neoplasms/genetics ; Liver Neoplasms/therapy ; Precision Medicine ; Artificial Intelligence ; Biomarkers, Tumor/genetics ; Liquid Biopsy
Chemical Substances	Biomarkers, Tumor
Language	English
Publishing date	2023-11-14
Publishing country	Mexico
Document type	Journal Article ; Review
ZDB-ID	2188733-0
ISSN	1665-2681
ISSN	1665-2681
DOI	10.1016/j.aohep.2023.101176
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Article ; Online: The role of Aurora kinase A in hepatocellular carcinoma: Unveiling the intriguing functions of a key but still underexplored factor in liver cancer.

Grisetti, Luca / Garcia, Clarissa J C / Saponaro, Anna A / Tiribelli, Claudio / Pascut, Devis

Cell proliferation

2024 , Page(s) e13641

Abstract: Aurora Kinase A (AURKA) plays a central role as a serine/threonine kinase in regulating cell cycle progression and mitotic functions. Over the years, extensive research has revealed the multifaceted roles of AURKA in cancer development and progression. ... ...

Abstract	Aurora Kinase A (AURKA) plays a central role as a serine/threonine kinase in regulating cell cycle progression and mitotic functions. Over the years, extensive research has revealed the multifaceted roles of AURKA in cancer development and progression. AURKA's dysregulation is frequently observed in various human cancers, including hepatocellular carcinoma (HCC). Its overexpression in HCC has been associated with aggressive phenotypes and poor clinical outcomes. This review comprehensively explores the molecular mechanisms underlying AURKA expression in HCC and its functional implications in cell migration, invasion, epithelial-to-mesenchymal transition, metastasis, stemness, and drug resistance. This work focuses on the clinical significance of AURKA as a diagnostic and prognostic biomarker for HCC. High levels of AURKA expression have been correlated with shorter overall and disease-free survival in various cohorts, highlighting its potential utility as a sensitive prognostic indicator. Recent insights into AURKA's role in modulating the tumour microenvironment, particularly immune cell recruitment, may provide valuable information for personalized treatment strategies. AURKA's critical involvement in modulating cellular pathways and its overexpression in cancer makes it an attractive target for anticancer therapies. This review discusses the evidence about novel and selective AURKA inhibitors for more effective treatments for HCC.
Language	English
Publishing date	2024-04-08
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	1064202-x
ISSN	1365-2184 ; 0008-8730 ; 0960-7722
ISSN (online)	1365-2184
ISSN	0008-8730 ; 0960-7722
DOI	10.1111/cpr.13641
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Article ; Online: Recent Hints on the Dual Role of Discs Large MAGUK Scaffold Protein 5 in Cancers and in Hepatocellular Carcinoma.

Andolfi, Chiara / Tiribelli, Claudio / Pascut, Devis

Frontiers in bioscience (Landmark edition)

2022 Volume 27, Issue 5, Page(s) 164

Abstract: Discs large MAGUK scaffold protein 5 (DLG5) is a multi-domain member of membrane-associated guanylate kinase (MAGUK) family, which plays a major role in the maintenance of cell epithelial polarity being part of the SCRIB-LGL-DLG complex. Although ... ...

Abstract	Discs large MAGUK scaffold protein 5 (DLG5) is a multi-domain member of membrane-associated guanylate kinase (MAGUK) family, which plays a major role in the maintenance of cell epithelial polarity being part of the SCRIB-LGL-DLG complex. Although polarity proteins have been generally considered tumor suppressors, recent discoveries led to reconsidering their role in cancer. This is also true for DLG5 in different cancer types, including hepatocellular carcinoma (HCC). In this cancer, DLG5 was negatively associated with malignant characteristics, however recent findings associated DLG5 expression with advanced stages of HCC.
MeSH term(s)	Carcinoma, Hepatocellular/genetics ; Guanylate Kinases/genetics ; Guanylate Kinases/metabolism ; Humans ; Liver Neoplasms/genetics ; Membrane Proteins/genetics ; Membrane Proteins/metabolism ; Phosphatidylinositol 3-Kinases ; Tumor Suppressor Proteins/genetics ; Tumor Suppressor Proteins/metabolism
Chemical Substances	DLG5 protein, human ; Membrane Proteins ; Tumor Suppressor Proteins ; Guanylate Kinases (EC 2.7.4.8)
Language	English
Publishing date	2022-05-30
Publishing country	Singapore
Document type	Journal Article ; Review
ZDB-ID	2704569-9
ISSN	2768-6698 ; 2768-6698
ISSN (online)	2768-6698
ISSN	2768-6698
DOI	10.31083/j.fbl2705164
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Article ; Online: Bilirubin-Induced Transcriptomic Imprinting in Neonatal Hyperbilirubinemia

Llido, John Paul / Fioriti, Emanuela / Pascut, Devis / Giuffrè, Mauro / Bottin, Cristina / Zanconati, Fabrizio / Tiribelli, Claudio / Gazzin, Silvia

Biology (Basel). 2023 June 08, v. 12, no. 6

2023

Abstract: Recent findings indicated aberrant epigenetic control of the central nervous system (CNS) development in hyperbilirubinemic Gunn rats as an additional cause of cerebellar hypoplasia, the landmark of bilirubin neurotoxicity in rodents. Because the ... ...

Abstract	Recent findings indicated aberrant epigenetic control of the central nervous system (CNS) development in hyperbilirubinemic Gunn rats as an additional cause of cerebellar hypoplasia, the landmark of bilirubin neurotoxicity in rodents. Because the symptoms in severely hyperbilirubinemic human neonates suggest other regions as privileged targets of bilirubin neurotoxicity, we expanded the study of the potential impact of bilirubin on the control of postnatal brain development to regions correlating with human symptoms. Histology, transcriptomic, gene correlation, and behavioral studies were performed. The histology revealed widespread perturbation 9 days after birth, restoring in adulthood. At the genetic level, regional differences were noticed. Bilirubin affected synaptogenesis, repair, differentiation, energy, extracellular matrix development, etc., with transient alterations in the hippocampus (memory, learning, and cognition) and inferior colliculi (auditory functions) but permanent changes in the parietal cortex. Behavioral tests confirmed the presence of a permanent motor disability. The data correlate well both with the clinic description of neonatal bilirubin-induced neurotoxicity, as well as with the neurologic syndromes reported in adults that suffered neonatal hyperbilirubinemia. The results pave the way for better deciphering the neurotoxic features of bilirubin and evaluating deeply the efficacy of new therapeutic approaches against the acute and long-lasting sequels of bilirubin neurotoxicity.
Keywords	adulthood ; bilirubin ; cerebellum ; cognition ; cortex ; energy ; epigenetics ; extracellular matrix ; genes ; hippocampus ; histology ; humans ; hyperbilirubinemia ; memory ; neurotoxicity ; synaptogenesis ; therapeutics ; transcriptomics
Language	English
Dates of publication	2023-0608
Publishing place	Multidisciplinary Digital Publishing Institute
Document type	Article ; Online
ZDB-ID	2661517-4
ISSN	2079-7737
ISSN	2079-7737
DOI	10.3390/biology12060834
Database	NAL-Catalogue (AGRICOLA)

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Article: HCC occurrence after DAA treatments: molecular tools to assess the post-treatment risk and surveillance.

Pascut, Devis / Pratama, Muhammad Yogi / Tiribelli, Claudio

Hepatic oncology

2020 Volume 7, Issue 2, Page(s) HEP21

Language	English
Publishing date	2020-06-22
Publishing country	England
Document type	Editorial
ZDB-ID	2756098-3
ISSN	2045-0931 ; 2045-0923
ISSN (online)	2045-0931
ISSN	2045-0923
DOI	10.2217/hep-2020-0010
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Circulating Long and Circular Noncoding RNA as Non-Invasive Diagnostic Tools of Hepatocellular Carcinoma.

Sukowati, Caecilia H C / Cabral, Loraine Kay D / Tiribelli, Claudio / Pascut, Devis

Biomedicines

2021 Volume 9, Issue 1

Abstract: Hepatocellular carcinoma (HCC) is one of the most common causes of cancer-related death worldwide, partially due to late diagnosis of the disease. Growing evidence in the field of biomarker discovery has shown the promising use of nucleic acid in the ... ...

Abstract	Hepatocellular carcinoma (HCC) is one of the most common causes of cancer-related death worldwide, partially due to late diagnosis of the disease. Growing evidence in the field of biomarker discovery has shown the promising use of nucleic acid in the early detection of many cancers, including HCC. Here, we review data on how various long noncoding RNAs (lncRNAs) and circular RNAs (circRNAs) could be used as a diagnostic tool for HCC being differentially expressed in HCC compared to non-HCC patients. These non-coding RNAs (ncRNAs) showed high stability in the blood being present as free-circulating molecules or encapsulated into exosomes. This review reports some recent evidence on the use of lncRNAs and circRNAs as possible diagnostic biomarkers for HCC. Further, their pathophysiological mechanism in liver carcinogenesis was also described, elucidating the complex regulatory networks making these ncRNAs of particular relevance for the study of liver malignancy cancer.
Language	English
Publishing date	2021-01-19
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2720867-9
ISSN	2227-9059
ISSN	2227-9059
DOI	10.3390/biomedicines9010090
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Article: Biomarkers for the Detection and Management of Hepatocellular Carcinoma in Patients Treated with Direct-Acting Antivirals.

Cabral, Loraine Kay D / Grisetti, Luca / Pratama, Muhammad Yogi / Tiribelli, Claudio / Pascut, Devis

Cancers

2022 Volume 14, Issue 11

Abstract: Hepatocellular carcinoma (HCC) is the sixth-most common type of cancer worldwide and chronic Hepatitis C virus (HCV) represents the main etiological factor in developed countries. HCV promotes hepatocarcinogenesis through persistent liver inflammation ... ...

Abstract	Hepatocellular carcinoma (HCC) is the sixth-most common type of cancer worldwide and chronic Hepatitis C virus (HCV) represents the main etiological factor in developed countries. HCV promotes hepatocarcinogenesis through persistent liver inflammation and dysregulation of cell signaling pathways. The introduction of direct-acting antivirals (DAAs) resulted in a significant improvement in the eradication of the virus, with an expected reduction of HCC incidence. However, the risk of HCC development can persist after DAA treatment. Recent studies have investigated the potential use of molecular biomarkers that predict HCC occurrence or recurrence helping the stratification of patients under surveillance. This review aimed to summarize all pre-clinical exploration of predictive biomarkers to identify DAA-treated patients at risk for HCC development. Dysregulated microRNAs, lncRNAs, histone modifications, cytokines, proteins, and sphingolipids represent various classes of HCC risk predictors identified in two different biological sources (tissue and serum). The non-invasive serum markers can provide a more accessible means to perform clinical monitoring and predict the risk of HCC. In addition, conditions like cirrhosis, predisposing to HCC, strongly correlate with most of the molecular predictors identified, supporting the value of these molecules as possible biomarkers of HCC in DAA-treated patients.
Language	English
Publishing date	2022-05-30
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers14112700
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Article: Bilirubin-Induced Transcriptomic Imprinting in Neonatal Hyperbilirubinemia.

Llido, John Paul / Fioriti, Emanuela / Pascut, Devis / Giuffrè, Mauro / Bottin, Cristina / Zanconati, Fabrizio / Tiribelli, Claudio / Gazzin, Silvia

Biology

2023 Volume 12, Issue 6

Abstract	Recent findings indicated aberrant epigenetic control of the central nervous system (CNS) development in hyperbilirubinemic Gunn rats as an additional cause of cerebellar hypoplasia, the landmark of bilirubin neurotoxicity in rodents. Because the symptoms in severely hyperbilirubinemic human neonates suggest other regions as privileged targets of bilirubin neurotoxicity, we expanded the study of the potential impact of bilirubin on the control of postnatal brain development to regions correlating with human symptoms. Histology, transcriptomic, gene correlation, and behavioral studies were performed. The histology revealed widespread perturbation 9 days after birth, restoring in adulthood. At the genetic level, regional differences were noticed. Bilirubin affected synaptogenesis, repair, differentiation, energy, extracellular matrix development, etc., with transient alterations in the hippocampus (memory, learning, and cognition) and inferior colliculi (auditory functions) but permanent changes in the parietal cortex. Behavioral tests confirmed the presence of a permanent motor disability. The data correlate well both with the clinic description of neonatal bilirubin-induced neurotoxicity, as well as with the neurologic syndromes reported in adults that suffered neonatal hyperbilirubinemia. The results pave the way for better deciphering the neurotoxic features of bilirubin and evaluating deeply the efficacy of new therapeutic approaches against the acute and long-lasting sequels of bilirubin neurotoxicity.
Language	English
Publishing date	2023-06-08
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2661517-4
ISSN	2079-7737
ISSN	2079-7737
DOI	10.3390/biology12060834
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: The Role of microRNAs in the Cisplatin- and Radio-Resistance of Cervical Cancer.

Masadah, Rina / Rauf, Syahrul / Pratama, Muhammad Yogi / Tiribelli, Claudio / Pascut, Devis

Cancers

2021 Volume 13, Issue 5

Abstract: Cervical cancer is the fourth leading cause of cancer-related death among women worldwide. The chemotherapeutical agent cisplatin, a small platinum-based compound, is considered as the standard therapy for locally advanced cervical cancer or recurrent ... ...

Abstract	Cervical cancer is the fourth leading cause of cancer-related death among women worldwide. The chemotherapeutical agent cisplatin, a small platinum-based compound, is considered as the standard therapy for locally advanced cervical cancer or recurrent cancers, sometimes in combination with radiotherapy or other drugs. However, drug resistance and radio-resistance phenomena could reduce the life expectancy of cervical cancer patients. Resistance mechanisms are complex and often involve multiple cellular pathways in which microRNAs (miRNAs) play a fundamental role. miRNAs are a class of endogenous non-coding small RNAs responsible for post-transcriptional gene regulation. Convincing evidence demonstrates that several deregulated miRNAs are important regulators in the onset of drug and radioresistance in cervical cancer, thus underlying their potential applications in a clinical setting. In this review, we summarized the mechanisms by which miRNAs affect both cisplatin and radioresistance in cervical cancer. We also described the regulatory loops between miRNAs and lncRNAs promoting drug resistance. Besides, we reported evidence for the role of miRNAs in sensitizing cancer cells to cisplatin-based chemotherapy, and provided some suggestions for the development of new combined therapies for cervical cancer.
Language	English
Publishing date	2021-03-09
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers13051168
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: HCV Proteins Modulate the Host Cell miRNA Expression Contributing to Hepatitis C Pathogenesis and Hepatocellular Carcinoma Development.

Pascut, Devis / Hoang, Minh / Nguyen, Nhu N Q / Pratama, Muhammad Yogi / Tiribelli, Claudio

Cancers

2021 Volume 13, Issue 10

Abstract: Hepatitis C virus (HCV) genome encodes for one long polyprotein that is processed by cellular and viral proteases to generate 10 polypeptides. The viral structural proteins include the core protein, and the envelope glycoproteins E1 and E2, present at ... ...

Abstract	Hepatitis C virus (HCV) genome encodes for one long polyprotein that is processed by cellular and viral proteases to generate 10 polypeptides. The viral structural proteins include the core protein, and the envelope glycoproteins E1 and E2, present at the surface of HCV particles. Non-structural (NS) proteins consist of NS1, NS2, NS3, NS4A, NS4B, NS5a, and NS5b and have a variable function in HCV RNA replication and particle assembly. Recent findings evidenced the capacity of HCV virus to modulate host cell factors to create a favorable environment for replication. Indeed, increasing evidence has indicated that the presence of HCV is significantly associated with aberrant miRNA expression in host cells, and HCV structural and non-structural proteins may be responsible for these alterations. In this review, we summarize the recent findings on the role of HCV structural and non-structural proteins in the modulation of host cell miRNAs, with a focus on the molecular mechanisms responsible for the cell re-programming involved in viral replication, immune system escape, as well as the oncogenic process. In this regard, structural and non-structural proteins have been shown to modulate the expression of several onco-miRNAs or tumor suppressor miRNAs.
Language	English
Publishing date	2021-05-19
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers13102485
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