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  1. Article: Stemness markers in hepatocellular carcinoma of Eastern vs. Western population: Etiology matters?

    Sukowati, Caecilia Hc / El-Khobar, Korri / Jasirwan, Chyntia Olivia Maurine / Kurniawan, Juferdy / Gani, Rino Alvani

    Annals of hepatology

    2023  Volume 29, Issue 1, Page(s) 101153

    Abstract: Hepatocellular carcinoma (HCC) is one of the most common cancers with a high mortality rate. HCC development is associated with its underlying etiologies, mostly caused by infection of chronic hepatitis B virus (HBV) and hepatitis C virus (HCV), alcohol, ...

    Abstract Hepatocellular carcinoma (HCC) is one of the most common cancers with a high mortality rate. HCC development is associated with its underlying etiologies, mostly caused by infection of chronic hepatitis B virus (HBV) and hepatitis C virus (HCV), alcohol, non-alcoholic fatty liver disease, and exposure to aflatoxins. These variables, together with human genetic susceptibility, contribute to HCC molecular heterogeneity, including at the cellular level. HCC initiation, tumor recurrence, and drug resistance rates have been attributed to the presence of liver cancer stem cells (CSC). This review summarizes available data regarding whether various HCC etiologies may be associated to the appearance of CSC biomarkers. It also described the genetic variations of tumoral tissues obtained from Western and Eastern populations, in particular to the oncogenic effect of HBV in the human genome.
    MeSH term(s) Humans ; Carcinoma, Hepatocellular/genetics ; Carcinoma, Hepatocellular/pathology ; Liver Neoplasms/genetics ; Liver Neoplasms/pathology ; Hepatitis B, Chronic/complications ; Neoplasm Recurrence, Local ; Hepatitis C/complications ; Hepatitis C/epidemiology ; Hepatitis B virus/genetics ; Hepatitis B/complications
    Language English
    Publishing date 2023-09-19
    Publishing country Mexico
    Document type Journal Article ; Review
    ZDB-ID 2188733-0
    ISSN 1665-2681
    ISSN 1665-2681
    DOI 10.1016/j.aohep.2023.101153
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

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  2. Article: Differential capacity of CD90+ cells in autophagy activation following chemotherapy in hepatocellular carcinoma.

    Do, Huy Q / Luong, An B / Bonazza, Deborah / Bottin, Cristina / Doan, Thao Pt / Tran, Long Dc / Truong, Nhung H / Tell, Gianluca / Pham, Hoa Lt / Tiribelli, Claudio / Sukowati, Caecilia Hc

    Annals of hepatology

    2020  Volume 19, Issue 6, Page(s) 645–652

    Abstract: Introduction and objectives: Analysis of cancer biomarkers is an important tool in developing targeted-therapy and in modulating chemoresistance. Here, we analyze the relevance of CD90, a marker of cancer stem cells (CSC) in hepatocellular carcinoma ( ... ...

    Abstract Introduction and objectives: Analysis of cancer biomarkers is an important tool in developing targeted-therapy and in modulating chemoresistance. Here, we analyze the relevance of CD90, a marker of cancer stem cells (CSC) in hepatocellular carcinoma (HCC) and its correlation with autophagy.
    Materials and methods: For in vivo study, 86 specimens were collected from 43 patients undergoing liver resections. In each patient, HCC nodule (HCC) and surrounding non-tumor (SNT) were collected. For in vitro study, HCC cells JHH6 subpopulations expressing CD90+ and CD90- were isolated using magnetic-sorter and confirmed by flow-cytometry. Upon doxorubicin treatment, autophagy turn-over was analyzed by RTqPCR for mRNA expression, Western blot for protein expression, and autophagosome staining for autophagy-flux. Cytotoxicity test was performed by MTT assay. Gene and protein analysis were performed in clinical samples together with immunohistostaining.
    Results: CD90 mRNA expression was higher in HCC than in SNT for 8-fold (p < 0.001). LC3-II protein was up-regulated in the HCC in comparison with the SNT (p < 0.05). In vitro model showed that CD90+ and CD90- cells had diverse expressions of autophagy-related genes. Upon doxorubicin treatment, autophagy was activated in both cells by increasing LC3-II protein expression, autophagic vacuoles, and dysregulation of autophagy-related mRNAs. A differential autophagic capacity was noticed between two subpopulations and it was correlated with cellular toxicity assay.
    Conclusions: We demonstrated the relevance of differential autophagy capacity of CD90+ cells in HCC. Autophagy was involved in cancer-defense mechanism against doxorubicin. Cancer promoting function of autophagy in CD90+ cells was also related to cancer environment.
    MeSH term(s) Antibiotics, Antineoplastic/therapeutic use ; Autophagy/drug effects ; Carcinoma, Hepatocellular/drug therapy ; Carcinoma, Hepatocellular/metabolism ; Carcinoma, Hepatocellular/pathology ; Cell Culture Techniques ; Cell Line, Tumor ; Doxorubicin/therapeutic use ; Female ; Humans ; Liver Neoplasms/drug therapy ; Liver Neoplasms/metabolism ; Liver Neoplasms/pathology ; Male ; Microtubule-Associated Proteins/metabolism ; Middle Aged ; Thy-1 Antigens/metabolism
    Chemical Substances Antibiotics, Antineoplastic ; MAP1LC3B protein, human ; Microtubule-Associated Proteins ; Thy-1 Antigens ; Doxorubicin (80168379AG)
    Language English
    Publishing date 2020-08-01
    Publishing country Mexico
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2188733-0
    ISSN 1665-2681
    ISSN 1665-2681
    DOI 10.1016/j.aohep.2020.07.007
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 6221: Show issues Location:
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    bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
    ab Jg. 2022: Lesesaal (EG)

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  3. Article ; Online: Differential capacity of CD90+ cells in autophagy activation following chemotherapy in hepatocellular carcinoma

    Huy Q Do / An B Luong / Deborah Bonazza / Cristina Bottin / Thao PT Doan / Long DC Tran / Nhung H Truong / Gianluca Tell / Hoa LT Pham / Claudio Tiribelli / Caecilia HC Sukowati

    Annals of Hepatology, Vol 19, Iss 6, Pp 645-

    2020  Volume 652

    Abstract: ABSTRACT: Introduction and Objectives. Analysis of cancer biomarkers is an important tool in developing targeted-therapy and in modulating chemoresistance. Here, we analyze the relevance of CD90, a marker of cancer stem cells (CSC) in hepatocellular ... ...

    Abstract ABSTRACT: Introduction and Objectives. Analysis of cancer biomarkers is an important tool in developing targeted-therapy and in modulating chemoresistance. Here, we analyze the relevance of CD90, a marker of cancer stem cells (CSC) in hepatocellular carcinoma (HCC) and its correlation with autophagy. Materials and Methods. For in vivo study, 86 specimens were collected from 43 patients undergoing liver resections. In each patient, HCC nodule (HCC) and surrounding non-tumor (SNT) were collected. For in vitro study, HCC cells JHH6 subpopulations expressing CD90+ and CD90- were isolated using magnetic-sorter and confirmed by flow-cytometry. Upon doxorubicin treatment, autophagy turn-over was analyzed by RTqPCR for mRNA expression, Western blot for protein expression, and autophagosome staining for autophagy-flux. Cytotoxicity test was performed by MTT assay. Gene and protein analysis were performed in clinical samples together with immunohistostaining. Results. CD90 mRNA expression was higher in HCC than in SNT for 8-fold (p < 0.001). LC3-II protein was up-regulated in the HCC in comparison with the SNT (p < 0.05). In vitro model showed that CD90+ and CD90- cells had diverse expressions of autophagy-related genes. Upon doxorubicin treatment, autophagy was activated in both cells by increasing LC3-II protein expression, autophagic vacuoles, and dysregulation of autophagy-related mRNAs. A differential autophagic capacity was noticed between two subpopulations and it was correlated with cellular toxicity assay. Conclusions. We demonstrated the relevance of differential autophagy capacity of CD90+ cells in HCC. Autophagy was involved in cancer-defense mechanism against doxorubicin. Cancer promoting function of autophagy in CD90+ cells was also related to cancer environment.
    Keywords hepatocellular carcinoma ; autophagy ; cancer stem cells ; CD90 ; chemoresistance ; Specialties of internal medicine ; RC581-951
    Language English
    Publishing date 2020-11-01T00:00:00Z
    Publisher Elsevier
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  4. Article ; Online: Hepatic cancer stem cells and drug resistance

    Caecilia HC Sukowati, Natalia Rosso, Lory S Crocè, Claudio Tiribelli

    World Journal of Hepatology, Vol 2, Iss 3, Pp 114-

    Relevance in targeted therapies for hepatocellular carcinoma

    2010  Volume 126

    Abstract: Hepatocellular carcinoma (HCC) is one of most common malignancies in the world. Systemic treatments for HCC, particularly for advanced stages, are limited by the drug resistance phenomenon which ultimately leads to therapy failure. Recent studies have ... ...

    Abstract Hepatocellular carcinoma (HCC) is one of most common malignancies in the world. Systemic treatments for HCC, particularly for advanced stages, are limited by the drug resistance phenomenon which ultimately leads to therapy failure. Recent studies have indicated an association between drug resistance and the existence of the cancer stem cells (CSCs) as tumor initiating cells. The CSCs are resistant to conventional chemotherapies and might be related to the mechanisms of the ATP Binding Cassette (ABC) transporters and alterations in the CSCs signaling pathways. Therefore, to contribute to the development of new HCC treatments, further information on the characterization of CSCs, the modulation of the ABC transporters expression and function and the signaling pathway involved in the self renewal, initiation and maintenance of the cancer are required. The combination of transporters modulators/inhibitors with molecular targeted therapies may be a potent strategy to block the tumoral progression. This review summarizes the association of CSCs, drug resistance, ABC transporters activities and changes in signaling pathways as a guide for future molecular therapy for HCC.
    Keywords Hepatocellular carcinoma ; Liver ; Cancer stem cells ; Drug resistance ; Hepatocellular carcinoma therapy ; Diseases of the digestive system. Gastroenterology ; RC799-869 ; Specialties of internal medicine ; RC581-951 ; Internal medicine ; RC31-1245 ; Medicine ; R ; DOAJ:Gastroenterology ; DOAJ:Medicine (General) ; DOAJ:Health Sciences
    Subject code 610
    Language English
    Publishing date 2010-03-01T00:00:00Z
    Publisher Baishideng Publishing Group Co. Limited
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  5. Article ; Online: Hepatic cancer stem cells and drug resistance: Relevance in targeted therapies for hepatocellular carcinoma.

    Sukowati, Caecilia Hc / Rosso, Natalia / Crocè, Lory S / Tiribelli, Claudio

    World journal of hepatology

    2010  Volume 2, Issue 3, Page(s) 114–126

    Abstract: Hepatocellular carcinoma (HCC) is one of most common malignancies in the world. Systemic treatments for HCC, particularly for advanced stages, are limited by the drug resistance phenomenon which ultimately leads to therapy failure. Recent studies have ... ...

    Abstract Hepatocellular carcinoma (HCC) is one of most common malignancies in the world. Systemic treatments for HCC, particularly for advanced stages, are limited by the drug resistance phenomenon which ultimately leads to therapy failure. Recent studies have indicated an association between drug resistance and the existence of the cancer stem cells (CSCs) as tumor initiating cells. The CSCs are resistant to conventional chemotherapies and might be related to the mechanisms of the ATP Binding Cassette (ABC) transporters and alterations in the CSCs signaling pathways. Therefore, to contribute to the development of new HCC treatments, further information on the characterization of CSCs, the modulation of the ABC transporters expression and function and the signaling pathway involved in the self renewal, initiation and maintenance of the cancer are required. The combination of transporters modulators/inhibitors with molecular targeted therapies may be a potent strategy to block the tumoral progression. This review summarizes the association of CSCs, drug resistance, ABC transporters activities and changes in signaling pathways as a guide for future molecular therapy for HCC.
    Language English
    Publishing date 2010-12-10
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2573703-X
    ISSN 1948-5182 ; 1948-5182
    ISSN (online) 1948-5182
    ISSN 1948-5182
    DOI 10.4254/wjh.v2.i3.114
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Gene and functional up-regulation of the BCRP/ABCG2 transporter in hepatocellular carcinoma.

    Sukowati, Caecilia Hc / Rosso, Natalia / Pascut, Devis / Anfuso, Beatrice / Torre, Giuliano / Francalanci, Paola / Crocè, Lory S / Tiribelli, Claudio

    BMC gastroenterology

    2012  Volume 12, Page(s) 160

    Abstract: Background: The Breast Cancer Resistance Protein (BCRP/ABCG2) is one member of ABC transporters proteins super family responsible of drug resistance. Since data on ABCG2 expression in liver malignances are scanty, here we report the expression of ABCG2 ... ...

    Abstract Background: The Breast Cancer Resistance Protein (BCRP/ABCG2) is one member of ABC transporters proteins super family responsible of drug resistance. Since data on ABCG2 expression in liver malignances are scanty, here we report the expression of ABCG2 in adult human hepatocellular carcinoma (HCC) in both in vivo and in vitro models with different degree of malignancy.
    Methods: In cell lines derived from human hepatocellular carcinoma, ABCG2 gene expression was assessed by reverse transcription quantitative real time PCR and function by Hoechst 33342 efflux assay; protein content was assessed by SDS-PAGE Western blot.
    Results: ABCG2 expression was found to be highest in the most undifferentiated cell lines, and this was related with a higher functional activity. ABCG2 expression was sensitive to antineoplastic drugs since exposure to 5 μM doxorubicin for 24 hours resulted in significant up-regulations of ABCG2 in all cell lines, particularly in those lines with low basal ABCG2 expression (p<0.01). The gene expression was also investigated in 51 adult liver tissues with HCC and related cirrhosis; normal liver tissue was used as control. ABCG2 gene expression was higher in HCC than both cirrhotic paired tissue and normal tissue. This up-regulation was greater (p<0.05) in pathological poorly differentiated grade G3/G4 than in well-differentiated G1/G2 HCC.
    Conclusions: Our results suggest a correlation of ABCG2 gene expression and differentiation stage both in human and HCC derived cell lines. The rapid up-regulation of ABCG2 to exposure to doxorubicin emphasizes the importance of this transporter in accounting for drug resistance in liver tumors.
    MeSH term(s) ATP Binding Cassette Transporter, Subfamily G, Member 2 ; ATP-Binding Cassette Transporters/genetics ; ATP-Binding Cassette Transporters/metabolism ; Antibiotics, Antineoplastic/pharmacology ; Carcinoma, Hepatocellular/genetics ; Carcinoma, Hepatocellular/metabolism ; Carcinoma, Hepatocellular/pathology ; Cell Differentiation ; Cell Survival/drug effects ; Doxorubicin/pharmacology ; Drug Resistance, Neoplasm/genetics ; Gene Expression ; Hep G2 Cells ; Humans ; Liver Cirrhosis/complications ; Liver Cirrhosis/genetics ; Liver Neoplasms/genetics ; Liver Neoplasms/metabolism ; Liver Neoplasms/pathology ; Neoplasm Grading ; Neoplasm Proteins/genetics ; Neoplasm Proteins/metabolism ; RNA, Messenger/metabolism ; Up-Regulation/drug effects
    Chemical Substances ABCG2 protein, human ; ATP Binding Cassette Transporter, Subfamily G, Member 2 ; ATP-Binding Cassette Transporters ; Antibiotics, Antineoplastic ; Neoplasm Proteins ; RNA, Messenger ; Doxorubicin (80168379AG)
    Language English
    Publishing date 2012-11-15
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ISSN 1471-230X
    ISSN (online) 1471-230X
    DOI 10.1186/1471-230X-12-160
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  7. Article ; Online: Gene and functional up-regulation of the BCRP/ABCG2 transporter in hepatocellular carcinoma

    Sukowati Caecilia HC / Rosso Natalia / Pascut Devis / Anfuso Beatrice / Torre Giuliano / Francalanci Paola / Crocè Lory S / Tiribelli Claudio

    BMC Gastroenterology, Vol 12, Iss 1, p

    2012  Volume 160

    Abstract: Abstract Background The Breast Cancer Resistance Protein (BCRP/ABCG2) is one member of ABC transporters proteins super family responsible of drug resistance. Since data on ABCG2 expression in liver malignances are scanty, here we report the expression of ...

    Abstract Abstract Background The Breast Cancer Resistance Protein (BCRP/ABCG2) is one member of ABC transporters proteins super family responsible of drug resistance. Since data on ABCG2 expression in liver malignances are scanty, here we report the expression of ABCG2 in adult human hepatocellular carcinoma (HCC) in both in vivo and in vitro models with different degree of malignancy. Methods In cell lines derived from human hepatocellular carcinoma, ABCG2 gene expression was assessed by reverse transcription quantitative real time PCR and function by Hoechst 33342 efflux assay; protein content was assessed by SDS-PAGE Western blot. Results ABCG2 expression was found to be highest in the most undifferentiated cell lines, and this was related with a higher functional activity. ABCG2 expression was sensitive to antineoplastic drugs since exposure to 5 μM doxorubicin for 24 hours resulted in significant up-regulations of ABCG2 in all cell lines, particularly in those lines with low basal ABCG2 expression (p<0.01). The gene expression was also investigated in 51 adult liver tissues with HCC and related cirrhosis; normal liver tissue was used as control. ABCG2 gene expression was higher in HCC than both cirrhotic paired tissue and normal tissue. This up-regulation was greater (p<0.05) in pathological poorly differentiated grade G3/G4 than in well-differentiated G1/G2 HCC. Conclusions Our results suggest a correlation of ABCG2 gene expression and differentiation stage both in human and HCC derived cell lines. The rapid up-regulation of ABCG2 to exposure to doxorubicin emphasizes the importance of this transporter in accounting for drug resistance in liver tumors.
    Keywords Liver cancer ; Drug resistance ; Gene expression ; Doxorubicin ; Diseases of the digestive system. Gastroenterology ; RC799-869 ; Specialties of internal medicine ; RC581-951 ; Internal medicine ; RC31-1245 ; Medicine ; R ; DOAJ:Gastroenterology ; DOAJ:Medicine (General) ; DOAJ:Health Sciences
    Subject code 616
    Language English
    Publishing date 2012-11-01T00:00:00Z
    Publisher BioMed Central
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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