5 results on '"Tania Hernáez-Alsina"'
Search Results
2. Risk of recurrence of hepatocellular carcinoma in patients treated with interferon-free antivirals
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Cassia Guedes-Leal, Tania Hernáez-Alsina, Maria Reig, Berta Caballol-Oliva, and Álvaro Díaz-González
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0301 basic medicine ,Oncology ,medicine.medical_specialty ,Carcinoma, Hepatocellular ,Cirrhosis ,Hepatitis C virus ,Population ,Disease ,medicine.disease_cause ,Antiviral Agents ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Hepatectomy ,Humans ,Medicine ,In patient ,Prospective Studies ,Risks and benefits ,education ,neoplasms ,Retrospective Studies ,education.field_of_study ,business.industry ,Interferon free ,Liver Neoplasms ,Hepatitis C, Chronic ,medicine.disease ,Embolization, Therapeutic ,digestive system diseases ,030104 developmental biology ,Hepatocellular carcinoma ,Disease Progression ,030211 gastroenterology & hepatology ,Interferons ,Neoplasm Recurrence, Local ,business - Abstract
Eradication of the hepatitis C virus (HCV) with interferon-free therapies (DAAs) has modified the course of the disease, as the rate of patients with compensated cirrhosis who achieve a sustained virological response exceeds 95%. However, the impact on development of hepatocellular carcinoma (HCC) is currently in dispute. This argument could be divided into different key points: the impact of DAA on rate of HCC recurrence, the temporal link between starting DAAs and HCC recurrence, and finally, the aggressive pattern of HCC. Therefore, the aim of this review is to analyse the available results in this population of patients from a clinical perspective where the risks and benefits of HCV eradication with DAA therapies are evaluated in patients with complete response of HCC.
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- 2019
3. Antioxidants Threaten Multikinase Inhibitor Efficacy against Liver Cancer by Blocking Mitochondrial Reactive Oxygen Species
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Anna Tutusaus, Tania Hernáez-Alsina, Maria Reig, Anna Colell, Albert Morales, Blanca Cucarull, Pablo García de Frutos, Montserrat Marí, Instituto de Salud Carlos III, Centro de Investigación Biomédica en Red Enfermedades Hepáticas y Digestivas (España), Centro Investigación Biomédica en Red Enfermedades Neurodegenerativas (España), Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), European Commission, and Generalitat de Catalunya
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Sorafenib ,Mitochondrial ROS ,Hepatocellular carcinoma ,Physiology ,Clinical Biochemistry ,BCL-2 ,Apoptosis ,RM1-950 ,tumor spheroids ,Mitochondrion ,medicine.disease_cause ,chemotherapy ,Biochemistry ,Article ,chemistry.chemical_compound ,Regorafenib ,medicine ,Chemotherapy ,oxidative stress ,glutathione ,Molecular Biology ,neoplasms ,chemistry.chemical_classification ,Reactive oxygen species ,Chemistry ,Mitophagy ,apoptosis ,Superoxide ,Cell Biology ,Glutathione ,hepatocellular carcinoma ,digestive system diseases ,Mitochondria ,mitochondria ,mitophagy ,Oxidative stress ,Cancer research ,Tumor spheroids ,Therapeutics. Pharmacology ,superoxide ,medicine.drug - Abstract
Sorafenib and regorafenib, multikinase inhibitors (MKIs) used as standard chemotherapeutic agents for hepatocellular carcinoma (HCC), generate reactive oxygen species (ROS) during cancer treatment. Antioxidant supplements are becoming popular additions to our diet, particularly glutathione derivatives and mitochondrial-directed compounds. To address their possible interference during HCC chemotherapy, we analyzed the effect of common antioxidants using hepatoma cell lines and tumor spheroids. In liver cancer cell lines, sorafenib and regorafenib induced mitochondrial ROS production and potent cell death after glutathione depletion. In contrast, cabozantinib only exhibited oxidative cell death in specific HCC cell lines. After sorafenib and regorafenib administration, antioxidants such as glutathione methyl ester and the superoxide scavenger MnTBAP decreased cell death and ROS production, precluding the MKI activity against hepatoma cells. Interestingly, sorafenib-induced mitochondrial damage caused PINK/Parkin-dependent mitophagy stimulation, altered by increased ROS production. Finally, in sorafenib-treated tumor spheroids, while ROS induction reduced tumor growth, antioxidant treatments favored tumor development. In conclusion, the anti-tumor activity of specific MKIs, such as regorafenib and sorafenib, is altered by the cellular redox status, suggesting that uncontrolled antioxidant intake during HCC treatment should be avoided or only endorsed to diminish chemotherapy-induced side effects, always under medical scrutiny., Study funded by grants from Instituto de Salud Carlos III (PI19/01410 to M.M., and PI19/00358 to M.R.), CIBEREHD and CIBERNED; Ministerio de Ciencia, Innovación y Universidades (RTI2018-095672-B-I00 to A.M. and P.G.F., and RTI2018-095572-B-100 to A.C.) and co-funded by FEDER (Fondo Europeo de Desarrollo Regional, Unión Europea); AGAUR (2017_SGR_177 to A.M.) and CERCA Programme/Generalitat de Catalunya
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- 2021
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4. Hepatocellular Carcinoma: Molecular Pathogenesis and Therapeutic Advances
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Blanca Cucarull, Anna Tutusaus, Patricia Rider, Tania Hernáez-Alsina, Carlos Cuño, Pablo García de Frutos, Anna Colell, Montserrat Marí, Albert Morales, Instituto de Salud Carlos III, Centro de Investigación Biomédica en Red Enfermedades Hepáticas y Digestivas (España), Centro Investigación Biomédica en Red Enfermedades Neurodegenerativas (España), Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), European Commission, Consejo Superior de Investigaciones Científicas (España), Generalitat de Catalunya, and Fundació La Marató de TV3
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Tyrosine kinase inhibitors ,Immune checkpoint inhibitors ,Molecular therapies ,Cancer Research ,Tumor microenvironment ,Oncology ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,Liver cancer ,RC254-282 ,digestive system diseases - Abstract
Hepatocellular carcinoma (HCC), the most common form of liver cancer, continues to be a serious medical problem with poor prognosis, without major therapeutic improvement for years and increasing incidence. Fortunately, advances in systemic treatment options are finally arriving for HCC patients. After a decade of sorafenib as a standard therapy for advanced HCC, several tyrosine kinase inhibitors (TKIs), antiangiogenic antibodies, and immune checkpoint inhibitors have reached the clinic. Although infections by hepatitis B virus and hepatitis C virus remain principal factors for HCC development, the rise of non-alcoholic steatohepatitis from diabetes mellitus or metabolic syndrome is impeding HCC decline. Knowledge of specific molecular mechanisms, based on the etiology and the HCC microenvironment that influence tumor growth and immune control, will be crucial for physician decision-making among a variety of drugs to prescribe. In addition, markers of treatment efficacy are needed to speed the movement of patients towards other potentially effective treatments. Consequently, research to provide scientific data for the evidence-based management of liver cancer is guaranteed in the coming years and discussed here., This research was funded by Instituto de Salud Carlos III, grant number PI19/01410 to M.M.; CIBEREHD and CIBERNED; Ministerio de Ciencia e Innovación, grant numbers RTI2018- 095672-B-I00 to A.M. and P.G.F. and RTI2018-095572-B-100 to A.C.; and co-funded by FEDER (Fondo Europeo de Desarrollo Regional, Unión Europea); Ayuda Extraordinaria CSIC 2021AEP095 to A.M. and P.G.F., AGAUR, grant number 2017_SGR_177 to A.M.; Fundació la Marató de TV3 to A.M.; and CERCA Programme/Generalitat de Catalunya.
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- 2022
5. Regorafenib Alteration of the BCL-xL/MCL-1 Ratio Provides a Therapeutic Opportunity for BH3-Mimetics in Hepatocellular Carcinoma Models
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Cucarull B, Tania Hernáez-Alsina, Montserrat Marí, Milica Stefanovic, Maria Reig, Jordi Bruix, Subías M, Anna Colell, Albert Morales, García de Frutos P, Anna Tutusaus, Loreto Boix, Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), Instituto de Salud Carlos III, European Commission, and Generalitat de Catalunya
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0301 basic medicine ,Sorafenib ,Cancer Research ,A-1331852 ,Bcl-xL ,Apoptosis ,lcsh:RC254-282 ,Article ,combination therapy ,Càncer de fetge ,liver cancer ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Bcl-2 family ,In vivo ,Regorafenib ,Medicine ,Combination therapy ,biology ,business.industry ,apoptosis ,Apoptosi ,medicine.disease ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,digestive system diseases ,Mitochondria ,mitochondria ,030104 developmental biology ,Oncology ,chemistry ,030220 oncology & carcinogenesis ,Hepatocellular carcinoma ,Cancer research ,biology.protein ,business ,Liver cancer ,medicine.drug - Abstract
© 2020 by the authors., Background: The multikinase inhibitor regorafenib, approved as second-line treatment for hepatocellular carcinoma (HCC) after sorafenib failure, may induce mitochondrial damage. BH3-mimetics, inhibitors of specific BCL-2 proteins, are valuable drugs in cancer therapy to amplify mitochondrial-dependent cell death. Methods: In in vitro and in vivo HCC models, we tested regorafenib’s effect on the BCL-2 network and the efficacy of BH3-mimetics on HCC treatment. Results: In hepatoma cell lines and Hep3B liver spheroids, regorafenib cytotoxicity was potentiated by BCL-xL siRNA transfection or pharmacological inhibition (A-1331852), while BCL-2 antagonism had no effect. Mitochondrial outer membrane permeabilization, cytochrome c release, and caspase-3 activation mediated A-1331852/regorafenib-induced cell death. In a patient-derived xenograft (PDX) HCC model, BCL-xL inhibition stimulated regorafenib activity, drastically decreasing tumor growth. Moreover, regorafenib-resistant HepG2 cells displayed increased BCL-xL and reduced MCL-1 expression, while A-1331852 reinstated regorafenib efficacy in vitro and in a xenograft mouse model. Interestingly, BCL-xL levels, associated with poor prognosis in liver and colorectal cancer, and the BCL-xL/MCL-1 ratio were detected as being increased in HCC patients. Conclusion: Regorafenib primes tumor cells to BH3-mimetic-induced cell death, allowing BCL-xL inhibition with A-1331852 or other strategies based on BCL-xL degradation to enhance regorafenib efficacy, offering a novel approach for HCC treatment, particularly for tumors with an elevated BCL-xL/MCL-1 ratio., This research was funded by Study funded by grants from Instituto de Salud Carlos III (PI16/00930 and PI19/01410), CIBEREHD and CIBERNED; Ministerio de Ciencia e Innovación (RTI2018-095672-B-I00 and RTI2018-095572-B-100) and co-funded by FEDER (MCI/AEI/FEDER, UE); AGAUR (2017_SGR_177 to A.M.) and CERCA Programme/Generalitat de Catalunya.
- Published
- 2020
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