scholarly journals Mutation spectrum of hepatocellular carcinoma from eastern-European patients betrays the impact of a complex exposome

2014 ◽  
Vol 25 (3) ◽  
pp. 256-263 ◽  
Author(s):  
Anna-Maria Tanase ◽  
Agnès Marchio ◽  
Traian Dumitrascu ◽  
Simona Dima ◽  
Vlad Herlea ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Mutation Spectrum ◽  
Eastern European ◽  
The Impact

Mechanisms of liver damage in COVID-19

2020 ◽  
Vol 1 (19) ◽  
pp. 39-46
Author(s):  
T. V. Pinchuk ◽  
N. V. Orlova ◽  
T. G. Suranova ◽  
T. I. Bonkalo
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Transplantation ◽  
Risk Factor ◽  
Liver Disease ◽  
Liver Function ◽  
Liver Damage ◽  
The World ◽  
Coronavirus Infection ◽  
The Impact ◽  
Analyze Data

At the end of 2019, a new coronavirus (SARS-CoV-2) was discovered in China, causing the coronavirus infection COVID-19. The ongoing COVID-19 pandemic poses a major challenge to health systems around the world. There is still little information on how infection affects liver function and the significance of pre-existing liver disease as a risk factor for infection and severe COVID-19. In addition, some drugs used to treat the new coronavirus infection are hepatotoxic. In this article, we analyze data on the impact of COVID-19 on liver function, as well as on the course and outcome of COVID-19 in patients with liver disease, including hepatocellular carcinoma, or those on immunosuppressive therapy after liver transplantation.

scholarly journals The impact of FGF19/FGFR4 signaling inhibition in antitumor activity of multi-kinase inhibitors in hepatocellular carcinoma

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Hiroaki Kanzaki ◽  
Tetsuhiro Chiba ◽  
Junjie Ao ◽  
Keisuke Koroki ◽  
Kengo Kanayama ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Molecular Mechanisms ◽  
Kinase Inhibitors ◽  
Progression Free Survival ◽  
Erk Signaling ◽  
Enzyme Linked Immunosorbent Assay ◽  
Antitumor Effects ◽  
The Impact

AbstractFGF19/FGFR4 autocrine signaling is one of the main targets for multi-kinase inhibitors (MKIs). However, the molecular mechanisms underlying FGF19/FGFR4 signaling in the antitumor effects to MKIs in hepatocellular carcinoma (HCC) remain unclear. In this study, the impact of FGFR4/ERK signaling inhibition on HCC following MKI treatment was analyzed in vitro and in vivo assays. Serum FGF19 in HCC patients treated using MKIs, such as sorafenib (n = 173) and lenvatinib (n = 40), was measured by enzyme-linked immunosorbent assay. Lenvatinib strongly inhibited the phosphorylation of FRS2 and ERK, the downstream signaling molecules of FGFR4, compared with sorafenib and regorafenib. Additional use of a selective FGFR4 inhibitor with sorafenib further suppressed FGFR4/ERK signaling and synergistically inhibited HCC cell growth in culture and xenograft subcutaneous tumors. Although serum FGF19high (n = 68) patients treated using sorafenib exhibited a significantly shorter progression-free survival and overall survival than FGF19low (n = 105) patients, there were no significant differences between FGF19high (n = 21) and FGF19low (n = 19) patients treated using lenvatinib. In conclusion, robust inhibition of FGF19/FGFR4 is of importance for the exertion of antitumor effects of MKIs. Serum FGF19 levels may function as a predictive marker for drug response and survival in HCC patients treated using sorafenib.

scholarly journals The Impact of Time Interval between Hepatic Resection and Liver Transplantation on Clinical Outcome in Patients with Hepatocellular Carcinoma

Cancers ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 2398
Author(s):  
Matteo Serenari ◽  
Enrico Prosperi ◽  
Marc-Antoine Allard ◽  
Michele Paterno ◽  
Nicolas Golse ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Transplantation ◽  
Hepatic Resection ◽  
Primary Outcome ◽  
Polynomial Regression ◽  
Secondary Outcome ◽  
Time Interval ◽  
Comprehensive Complication Index ◽  
Fractional Polynomial ◽  
The Impact

Hepatic resection (HR) for hepatocellular carcinoma (HCC) may require secondary liver transplantation (SLT). However, a previous HR is supposed to worsen post-SLT outcomes. Data of patients treated by SLT between 2000 and 2018 at two tertiary referral centers were analyzed. The primary outcome of the study was to analyze the impact of HR on post-LT complications. A Comprehensive Complication Index ≥ 29.6 was chosen as cutoff. The secondary outcome was HCC-related death by means of competing-risk regression analysis. In the study period, 140 patients were included. Patients were transplanted in a median of 23 months after HR (IQR 14–41). Among all the features analyzed regarding the prior HR, only time interval between HR and SLT (time HR-SLT) was an independent predictor of severe complications after LT (OR = 0.98, p < 0.001). According to fractional polynomial regression, the probability of severe complications increased up to 15 months after HR (43%), then slowly decreased over time (OR = 0.88, p < 0.001). There was no significant association between HCC-related death and time HR-SLT at the multivariable competing risks regression model (SHR, 1.06; 95% CI: 0.69–1.62, p = 0.796). This study showed that time HR-SLT was key in predicting complications after LT, without affecting HCC-related death.

scholarly journals Combining tissue and circulating tumor DNA increases the detection rate of a CTNNB1 mutation in hepatocellular carcinoma

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Stine Karlsen Oversoe ◽  
Michelle Simone Clement ◽  
Britta Weber ◽  
Henning Grønbæk ◽  
Stephen Jacques Hamilton-Dutoit ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Mutation Rate ◽  
Detection Rate ◽  
Tumor Tissue ◽  
Circulating Tumor Dna ◽  
Treatment Modalities ◽  
Advanced Hepatocellular Carcinoma ◽  
Tissue Samples ◽  
The Impact ◽  
Tumor Dna

Abstract Background and aims Studies suggest that mutations in the CTNNB1 gene are predictive of response to immunotherapy, an emerging therapy for advanced hepatocellular carcinoma (HCC). Analysis of circulating tumor DNA (ctDNA) offers the possibility of serial non-invasive mutational profiling of tumors. Combining tumor tissue and ctDNA analysis may increase the detection rate of mutations. This study aimed to evaluate the frequency of the CTNNB1 p.T41A mutation in ctDNA and tumor samples from HCC patients and to evaluate the concordance rates between plasma and tissue. We further evaluated changes in ctDNA after various HCC treatment modalities and the impact of the CTNNB1 p.T41A mutation on the clinical course of HCC. Methods We used droplet digital PCR to analyze plasma from 95 patients and the corresponding tumor samples from 37 patients during 3 years follow up. Results In tumor tissue samples, the mutation rate was 8.1% (3/37). In ctDNA from HCC patients, the CTNNB1 mutation rate was 9.5% (9/95) in the pre-treatment samples. Adding results from plasma analysis to the subgroup of patients with available tissue samples, the mutation detection rate increased to 13.5% (5/37). There was no difference in overall survival according to CTNNB1 mutational status. Serial testing of ctDNA suggested a possible clonal evolution of HCC or arising multicentric tumors with separate genetic profiles in individual patients. Conclusion Combining analysis of ctDNA and tumor tissue increased the detection rate of CTNNB1 mutation in HCC patients. A liquid biopsy approach may be useful in a tailored therapy of HCC.

scholarly journals Alpha-Fetoprotein- and CD40Ligand-Expressing Dendritic Cells for Immunotherapy of Hepatocellular Carcinoma

Cancers ◽  
2021 ◽  
Vol 13 (13) ◽  
pp. 3375
Author(s):  
Annabelle Vogt ◽  
Farsaneh Sadeghlar ◽  
Tiyasha H. Ayub ◽  
Carlo Schneider ◽  
Christian Möhring ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
T Cells ◽  
Dendritic Cells ◽  
Tumor Regression ◽  
Combined Therapy ◽  
Term Survival ◽  
Effector Cells ◽  
Tumor Environment ◽  
The Impact

Dendritic cells (DC) as professional antigen presenting cells are able to prime T-cells against the tumor-associated antigen α-fetoprotein (AFP) for immunotherapy of hepatocellular carcinoma (HCC). However, a strong immunosuppressive tumor environment limits their efficacy in patients. The co-stimulation with CD40Ligand (CD40L) is critical in the maturation of DC and T-cell priming. In this study, the impact of intratumoral (i.t.) CD40L-expressing DC to improve vaccination with murine (m)AFP-transduced DC (Ad-mAFP-DC) was analyzed in subcutaneous (s.c.) and orthotopic murine HCC. Murine DC were adenovirally transduced with Ad-mAFP or Ad-CD40L. Hepa129-mAFP-cells were injected into the right flank or the liver of C3H-mice to induce subcutaneous (s.c.) and orthotopic HCC. For treatments, 106 Ad-mAFP-transduced DC were inoculated s.c. followed by 106 CD40L-expressing DC injected intratumorally (i.t.). S.c. inoculation with Ad-mAFP-transduced DC, as vaccine, induced a delay of tumor-growth of AFP-positive HCC compared to controls. When s.c.-inoculation of Ad-mAFP-DC was combined with i.t.-application of Ad-CD40L-DC synergistic antitumoral effects were observed and complete remissions and long-term survival in 62% of tumor-bearing animals were achieved. Analysis of the tumor environment at different time points revealed that s.c.-vaccination with Ad-mAFP-DC seems to stimulate tumor-specific effector cells, allowing an earlier recruitment of effector T-cells and a Th1 shift within the tumors. After i.t. co-stimulation with Ad-CD40L-DC, production of Th1-cytokines was strongly increased and accompanied by a robust tumor infiltration of mature DC, activated CD4+-, CD8+-T-cells as well as reduction of regulatory T-cells. Moreover, Ad-CD40L-DC induced tumor cell apoptosis. Intratumoral co-stimulation with CD40L-expressing DC significantly improves vaccination with Ad-mAFP-DC in pre-established HCC in vivo. Combined therapy caused an early and strong Th1-shift in the tumor environment as well as higher tumor apoptosis, leading to synergistic tumor regression of HCC. Thus, CD40L co-stimulation represents a promising tool for improving DC-based immunotherapy of HCC.

scholarly journals Two Metabolomics Phenotypes of Human Hepatocellular Carcinoma in Non-Alcoholic Fatty Liver Disease According to Fibrosis Severity

Metabolites ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 54
Author(s):  
Benjamin Buchard ◽  
Camille Teilhet ◽  
Natali Abeywickrama Samarakoon ◽  
Sylvie Massoulier ◽  
Juliette Joubert-Zakeyh ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Monounsaturated Fatty Acids ◽  
Metabolic Reprogramming ◽  
Resonance Spectroscopy ◽  
Alcoholic Fatty Liver ◽  
The Impact ◽  
Alcoholic Fatty Liver Disease

Non-Alcoholic Fatty Liver Disease (NAFLD) is considered as the forthcoming predominant cause for hepatocellular carcinoma (HCC). NAFLD-HCC may rise in non-cirrhotic livers in 40 to 50% of patients. The aim of this study was to identify different metabolic pathways of HCC according to fibrosis level (F0F1 vs. F3F4). A non-targeted metabolomics strategy was applied. We analyzed 52 pairs of human HCC and adjacent non-tumoral tissues which included 26 HCC developed in severe fibrosis or cirrhosis (F3F4) and 26 in no or mild fibrosis (F0F1). Tissue extracts were analyzed using 1H-Nuclear Magnetic Resonance spectroscopy. An optimization evolutionary method based on genetic algorithm was used to identify discriminant metabolites. We identified 34 metabolites differentiating the two groups of NAFLD-HCC according to fibrosis level, allowing us to propose two metabolomics phenotypes of NAFLD-HCC. We showed that HCC-F0F1 mainly overexpressed choline derivatives and glutamine, whereas HCC-F3F4 were characterized by a decreased content of monounsaturated fatty acids (FA), an increase of saturated FA and an accumulation of branched amino acids. Comparing HCC-F0F1 and HCC-F3F4, differential expression levels of glucose, choline derivatives and phosphoethanolamine, monounsaturated FA, triacylglycerides were identified as specific signatures. Our metabolomics analysis of HCC tissues revealed for the first time two phenotypes of HCC developed in NAFLD according to fibrosis level. This study highlighted the impact of the underlying liver disease on metabolic reprogramming of the tumor.

scholarly journals Does a National Innovation System Encourage Sustainability? Lessons from the Construction Industry in Serbia

2021 ◽  
Vol 13 (7) ◽  
pp. 3591
Author(s):  
Marija Mosurović Ružičić ◽  
Mirjana Miletić ◽  
Marina Dobrota
Keyword(s):  
Energy Efficiency ◽  
Construction Industry ◽  
Innovation System ◽  
Business Environment ◽  
National Innovation System ◽  
Eastern European ◽  
System Perspective ◽  
Modern Business ◽  
Eastern European Countries ◽  
The Impact

Influences from the modern business environment indicate the need for the incorporation of sustainability concepts from an innovation system perspective. In the presented research, we emphasize the energy efficiency concept within the frame of sustainability and innovation. The aim of this research was to underline and explore the relationships between innovation, energy efficiency, and sustainability in the construction industry. To answer the research questions, a questionnaire was created to explore the impact of the energy efficiency certification process on the innovation behavior of construction industry enterprises in Serbia. The results show that energy efficiency has supported innovation, and that there exists a relationship between sustainability and innovativeness in the construction industry. Applying energy efficiency passports has influenced the co-operation of enterprises in the construction sector and other actors in the national innovation system in Serbia. The innovation concept demonstrates that enterprises in the construction industry should be observed as a part of the wider picture—the national innovation system. In turn, the specific context of a particular national innovation system should be seen within the wider picture of national innovation systems of Central and Eastern European Countries (CEECs).

scholarly journals The Impact of Geography in Hepatocellular Carcinoma: A Retrospective Population Based Study

2021 ◽  
Vol 28 (1) ◽  
pp. 396-404
Author(s):  
Irene S. Yu ◽  
Shiru L. Liu ◽  
Valeriya Zaborska ◽  
Tyler Raycraft ◽  
Sharlene Gill ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Retrospective Chart Review ◽  
Population Based ◽  
Tumor Board ◽  
Treatment Center ◽  
Population Based Study ◽  
Therapeutic Modalities ◽  
Quaternary Center ◽  
Statistics Canada ◽  
The Impact

Background: The treatment of hepatocellular carcinoma (HCC) includes different therapeutic modalities and multidisciplinary tumor board reviews. The impact of geography and treatment center type (quaternary vs. non-quaternary) on access to care is unclear. Methods: A retrospective chart review was performed on HCC patients who received sorafenib in British Columbia from 2008 to 2016. Patients were grouped by Statistics Canada population center (PC) size criteria: large PC (LPC), medium PC (MPC), and small PC (SPC). Access to specialists, receipt of liver-directed therapies, and survival outcomes were compared between the groups. Results: Of 286 patients, the geographical distribution was: LPC: 75%; MPC: 16%; and SPC: 9%. A higher proportion of Asians (51% vs. 9% vs. 4%; p < 0.001), Child–Pugh A (94% vs. 83% vs. 80%; p = 0.022), and hepatitis B (37% vs. 15% vs. 4%; p < 0.001) was observed in LPC vs. MPC vs. SPC, respectively. LPC patients were more likely referred to a hepatologist (62% vs. 48% vs. 40%; p = 0.031) and undergo transarterial chemoembolization (TACE) (43% vs. 24% vs. 24%; p = 0.018). Sixty percent were treated at a quaternary center, and the median overall survival (OS) was higher for patients treated at a quaternary vs. non-quaternary center (28.0 vs. 14.6 months, respectively; p < 0.001) but similar when compared by PC size. Treatment at a quaternary center predicted an improved survival on multivariate analysis (hazard ratio (HR): 0.652; 95% confidence interval (CI): 0.503–0.844; p = 0.001). Conclusions: Geography did not appear to impact OS but patients from LPC were more likely to be referred to hepatology and undergo TACE. Treatment at a quaternary center was associated with an improved survival.

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