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  1. Article: Immune checkpoint and angiogenic inhibitors for the treatment of hepatocellular carcinoma: It takes two to tangle.

    Sukowati, Caecilia / Cabral, Loraine Kay D / Tiribelli, Claudio

    Annals of hepatology

    2022  Volume 27, Issue 5, Page(s) 100740

    Abstract: Immunotherapy represents an effective and promising option in various cancers, including in hepatocellular carcinoma (HCC). The immune checkpoint inhibitors (ICIs) have shown a remarkable breakthrough in the last decade, in addition to molecular targeted ...

    Abstract Immunotherapy represents an effective and promising option in various cancers, including in hepatocellular carcinoma (HCC). The immune checkpoint inhibitors (ICIs) have shown a remarkable breakthrough in the last decade, in addition to molecular targeted therapy of angiogenesis such as tyrosine kinases inhibitors. ICIs provide new regimen that can be applied in different stages of the disease. In parallel, HCC progression is related to the tumor microenvironment (TME), involving the cross-talk between various cellular and non-cellular components within the TME niche. It appears logical to synergistically target several HCC components to increase the efficacy of the treatment. In this paper, we summarize evidence that the combination therapy of ICIs and angiogenesis inhibitors would be a potentially better strategy for HCC treatment.
    MeSH term(s) Angiogenesis Inhibitors/therapeutic use ; Carcinoma, Hepatocellular/pathology ; Humans ; Immunotherapy ; Liver Neoplasms/pathology ; Tumor Microenvironment
    Chemical Substances Angiogenesis Inhibitors
    Language English
    Publishing date 2022-07-06
    Publishing country Mexico
    Document type Journal Article
    ZDB-ID 2188733-0
    ISSN 1665-2681
    ISSN 1665-2681
    DOI 10.1016/j.aohep.2022.100740
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article: Sorafenib Resistance in Hepatocellular Carcinoma: The Relevance of Genetic Heterogeneity.

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

    Cancers

    2020  Volume 12, Issue 6

    Abstract: Despite advances in biomedicine, the incidence and the mortality of hepatocellular carcinoma (HCC) remain high. The majority of HCC cases are diagnosed in later stages leading to the less than optimal outcome of the treatments. Molecular targeted therapy ...

    Abstract Despite advances in biomedicine, the incidence and the mortality of hepatocellular carcinoma (HCC) remain high. The majority of HCC cases are diagnosed in later stages leading to the less than optimal outcome of the treatments. Molecular targeted therapy with sorafenib, a dual-target inhibitor targeting the serine-threonine kinase Raf and the tyrosine kinases VEGFR/PDGFR, is at present the main treatment for advanced-stage HCC, either in a single or combinatory regimen. However, it was observed in a large number of patients that its effectiveness is hampered by drug resistance. HCC is highly heterogeneous, within the tumor and among individuals, and this influences disease progression, classification, prognosis, and naturally cellular susceptibility to drug resistance. This review aims to provide an insight on how HCC heterogeneity influences the different primary mechanisms of chemoresistance against sorafenib including reduced drug intake, enhanced drug efflux, intracellular drug metabolism, alteration of molecular targets, activation/inactivation of signaling pathways, changes in the DNA repair machinery, and negative balance between apoptosis and survival of the cancer cells. The diverse variants, mutations, and polymorphisms in molecules and their association with drug response can be a helpful tool in treatment decision making. Accordingly, the existence of heterogeneous biomarkers in the tumor must be considered to strengthen multi-target strategies in patient-tailored treatment.
    Language English
    Publishing date 2020-06-15
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2527080-1
    ISSN 2072-6694
    ISSN 2072-6694
    DOI 10.3390/cancers12061576
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. 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
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. 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
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: PD-L1 Downregulation and DNA Methylation Inhibition for Molecular Therapy against Cancer Stem Cells in Hepatocellular Carcinoma.

    Sukowati, Caecilia / Cabral, Loraine Kay D / Anfuso, Beatrice / Dituri, Francesco / Negro, Roberto / Giannelli, Gianluigi / Tiribelli, Claudio

    International journal of molecular sciences

    2023  Volume 24, Issue 17

    Abstract: Hepatocellular carcinoma (HCC) is a heterogeneous cancer characterized by various cellular subtypes. This study investigates the potential of a combination strategy using immunotherapy and epigenetic reprogramming against HCC. We used a transgenic HCC ... ...

    Abstract Hepatocellular carcinoma (HCC) is a heterogeneous cancer characterized by various cellular subtypes. This study investigates the potential of a combination strategy using immunotherapy and epigenetic reprogramming against HCC. We used a transgenic HCC mouse C57BL/6J-TG(ALB1HBV)44BRI/J to assess the dynamics of the programmed death receptor and its ligand (PD-1/PD-L1) and DNA methylation markers. In parallel, PD-L1 RNA silencing was performed in various human HCC cell lines, while combination therapy was performed in a co-culture system using long-term exposure of 5-Azacytidine (5-AZA) and an anti-PD-L1. Data from the mouse model showed that the expressions of
    MeSH term(s) Humans ; Animals ; Mice ; Mice, Inbred C57BL ; Carcinoma, Hepatocellular/drug therapy ; Carcinoma, Hepatocellular/genetics ; DNA Methylation ; Down-Regulation ; Liver Neoplasms/drug therapy ; Liver Neoplasms/genetics ; Azacitidine/pharmacology ; Azacitidine/therapeutic use
    Chemical Substances Azacitidine (M801H13NRU)
    Language English
    Publishing date 2023-08-29
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2019364-6
    ISSN 1422-0067 ; 1422-0067 ; 1661-6596
    ISSN (online) 1422-0067
    ISSN 1422-0067 ; 1661-6596
    DOI 10.3390/ijms241713357
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article: Network Analysis for the Discovery of Common Oncogenic Biomarkers in Liver Cancer Experimental Models.

    Cabral, Loraine Kay D / Giraudi, Pablo J / Giannelli, Gianluigi / Dituri, Francesco / Negro, Roberto / Tiribelli, Claudio / Sukowati, Caecilia H C

    Biomedicines

    2023  Volume 11, Issue 2

    Abstract: Hepatocellular carcinoma (HCC) is a malignancy marked by heterogeneity. This study aimed to discover target molecules for potential therapeutic efficacy that may encompass HCC heterogeneity. In silico analysis using published datasets identified 16 proto- ...

    Abstract Hepatocellular carcinoma (HCC) is a malignancy marked by heterogeneity. This study aimed to discover target molecules for potential therapeutic efficacy that may encompass HCC heterogeneity. In silico analysis using published datasets identified 16 proto-oncogenes as potential pharmacological targets. We used an immortalized hepatocyte (IHH) and five HCC cell lines under two subtypes: S1/TGFβ-Wnt-activated (HLE, HLF, and JHH6) and the S2/progenitor subtype (HepG2 and Huh7). Three treatment modalities, 5 µM 5-Azacytidine, 50 µM Sorafenib, and 20 nM PD-L1 gene silencing, were evaluated in vitro. The effect of treatments on the proto-oncogene targets was assessed by gene expression and Western blot analysis. Our results showed that 10/16 targets were upregulated in HCC cells, where cells belonging to the S2/progenitor subtype had more upregulated targets compared to the S1/TGFβ-Wnt-activated subtype (81% vs. 62%, respectively). Among the targets, FGR was consistently down-regulated in the cell lines following the three different treatments. Sorafenib was effective to down-regulate targets in S2/progenitor subtype while PD-L1 silencing was able to decrease targets in all HCC subtypes, suggesting that this treatment strategy may comprise cellular heterogeneity. This study strengthens the relevance of liver cancer cellular heterogeneity in response to cancer therapies.
    Language English
    Publishing date 2023-01-25
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2720867-9
    ISSN 2227-9059
    ISSN 2227-9059
    DOI 10.3390/biomedicines11020342
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article: The Relevance of

    Cabral, Loraine Kay D / Reyes, Peter Andrew C / Crocè, Lory S / Tiribelli, Claudio / Sukowati, Caecilia H C

    Diagnostics (Basel, Switzerland)

    2021  Volume 11, Issue 10

    Abstract: The suppressor of cytokine signaling 1 ( ...

    Abstract The suppressor of cytokine signaling 1 (
    Language English
    Publishing date 2021-10-02
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2662336-5
    ISSN 2075-4418
    ISSN 2075-4418
    DOI 10.3390/diagnostics11101825
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article: MutL homolog 1 methylation and microsatellite instability in sporadic colorectal tumors among Filipinos.

    Cabral, Loraine Kay D / Mapua, Cynthia A / Natividad, Filipinas F / Sukowati, Caecilia H C / Cortez, Edgardo R / Enriquez, Ma Luisa D

    World journal of gastrointestinal oncology

    2022  Volume 13, Issue 12, Page(s) 2101–2113

    Abstract: Background: Colorectal cancer (CRC) ranks third in terms of incidence and second in mortality worldwide. In CRC, the silencing of mismatch repair genes, including the mutL homolog 1 (: Aim: To investigate the significance of the MSI status and : ... ...

    Abstract Background: Colorectal cancer (CRC) ranks third in terms of incidence and second in mortality worldwide. In CRC, the silencing of mismatch repair genes, including the mutL homolog 1 (
    Aim: To investigate the significance of the MSI status and
    Methods: Fifty-four sporadic CRC patients with complete clinical data were included in this study. Genomic DNA from CRC tumor biopsies and their normal tissue counterparts were profiled for MSI by high resolution melting (HRM) analysis using the Bethesda Panel of Markers (BAT25, BAT26, D2S123, D5S346, and D17S250).
    Results: hMLH1
    Conclusion: This study showed the clinical significance of
    Language English
    Publishing date 2022-01-13
    Publishing country China
    Document type Journal Article
    ZDB-ID 2573696-6
    ISSN 1948-5204
    ISSN 1948-5204
    DOI 10.4251/wjgo.v13.i12.2101
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: The mRNA Distribution of Cancer Stem Cell Marker CD90/Thy-1 Is Comparable in Hepatocellular Carcinoma of Eastern and Western Populations.

    Luong, An B / Do, Huy Q / Tarchi, Paola / Bonazza, Deborah / Bottin, Cristina / Cabral, Loraine Kay D / Tran, Long D C / Doan, Thao P T / Crocè, Lory S / Pham, Hoa L T / Tiribelli, Claudio / Sukowati, Caecilia H C

    Cells

    2020  Volume 9, Issue 12

    Abstract: Epidemiology of hepatocellular carcinoma (HCC) showed a correlation between incidence and geographical-relevant risk factors. This study aims to compare the distributions of cancer stem cells (CSC) in two distant populations in Asia and Europe. We ... ...

    Abstract Epidemiology of hepatocellular carcinoma (HCC) showed a correlation between incidence and geographical-relevant risk factors. This study aims to compare the distributions of cancer stem cells (CSC) in two distant populations in Asia and Europe. We analyzed 52 and 43 selected HCC patients undergoing hepatectomy in Ho Chi Minh City (Vietnam) and Trieste (Italy). Each patient sample consisted of HCC, peri-HCC, and non-tumoral (distal) tissue. Demographic data were recorded together with clinical findings. The protocol for the collection of tissue samples and RNA was standardized in both laboratories and gene expression analysis was performed in a single laboratory with identical PCR conditions. Baseline data showed comparable laboratory findings between the two cohorts. mRNA distribution showed a comparable pattern of all CSC markers analyzed with the expression of CD90 progressively increasing from distal and peri-HCC to be highest in HCC (
    MeSH term(s) Aged ; Biomarkers, Tumor/genetics ; Biomarkers, Tumor/metabolism ; Carcinoma, Hepatocellular/genetics ; Carcinoma, Hepatocellular/virology ; Cohort Studies ; Female ; Gene Expression Regulation, Neoplastic ; Hepatitis B/complications ; Hepatitis B/genetics ; Humans ; Liver Neoplasms/genetics ; Liver Neoplasms/virology ; Male ; Middle Aged ; Neoplastic Stem Cells/metabolism ; Neoplastic Stem Cells/pathology ; Prognosis ; RNA, Messenger/genetics ; RNA, Messenger/metabolism ; Thy-1 Antigens/genetics ; Thy-1 Antigens/metabolism
    Chemical Substances Biomarkers, Tumor ; RNA, Messenger ; Thy-1 Antigens
    Language English
    Publishing date 2020-12-12
    Publishing country Switzerland
    Document type Comparative Study ; Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2661518-6
    ISSN 2073-4409 ; 2073-4409
    ISSN (online) 2073-4409
    ISSN 2073-4409
    DOI 10.3390/cells9122672
    Database MEDical Literature Analysis and Retrieval System OnLINE

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