Search

Background: This study aims to compare the efficacy of navigator-gated three-dimensional T1-weighted gradient-echo sequences (NAV) with standard breath-hold T1-weighted gradient-echo sequences (BH) for the detection of hepatocellular carcinoma (HCC) nodules in patients with chronic viral hepatitis undergoing magnetic resonance imaging (MRI) with gadolinium ethoxybenzyl-diethylenetriaminepentaacetic acid (Gd-EOB-DTPA). Methods: From May 2022 to November 2023, fifty-eight patients were included in this retrospective study. Eligible patients had chronic viral hepatitis and at least one hepatic nodule of one cm or larger detected by ultrasound. Each patients underwent MRI that included NAV and BH sequences obtained by using various flip angles (FA) ranging from 10° to 40° post Gd-EOB-DTPA administration. Three independent radiologists performed qualitative analysis evaluating the clearness of the image, the presence of artifacts, the diagnostic reliability of the sequences, and the contrast-to-noise ratio (CNR) between lesions and liver, as well as between liver and spleen. Results: NAV sequences at a FA of 40° have demonstrated the highest agreement across all quality parameters (p < 0.001). A comparison of CNR between hypointense lesions and liver tissue showed decreasing values with increase FA, notably in NAV sequences. Statistically significant differences were observed among the sequences: BH 10° 0.73 ± 0.17; BH 30° 0.68 ± 0.17; BH 40° 0.68 ± 0.15; NAV 25° 0.62 ± 0.18; NAV 40° 0.56 ± 0.17. Although sequences with higher FA have shown an increase in CNR and contrast between liver and spleen, no statistically significant differences have been detected between BH and NAV with 40° of FA. Conclusions: The study highlighted the diagnostic superiority of NAV over BH sequences with a 40° FA in assessing image quality and enhancement in malignant liver nodules of cirrhotic patients. Incorporating one of these sequences into MRI protocols is recommended for enhanced diagnostic clarity, which is critical for informed surgical planning. This could facilitate more precise interventions, potentially improving surgical outcomes in the management of hepatocellular carcinoma. [ABSTRACT FROM AUTHOR]

Liver cancer is the most lethal form of cancer and carries a high risk of death around the world. Goniothalamin (GTN) is a styryl-lactone that possesses antiproliferative and apoptotic activity. The molecular action of GTN is not yet fully evaluated. Thus, our research has been intended to assess the chemopreventive and apoptotic activities of diethylnitrosamine (DEN)-induced hepatocellular carcinoma (HCC) in rats. Rats were separated into 4 groups: control, DEN only, DEN + GTN (30 mg/kg bw), and GTN (30 mg/kg bw) alone. We evaluated body weight, liver weight, tumor incidence, hepatic toxic markers, antioxidants, inflammatory cytokines, histopathology, immunohistochemistry, and Western blot studies. DEN lessened body weight, antioxidants, and apoptosis, whereas it elevated tumor incidence, toxic markers, cytokines, and Bcl-2 expression. GTN treatment maintains body weight, liver weight, and antioxidant levels, and it also prevents tumor incidence, oxidative stress, toxic markers, pro-inflammatory cytokines, and histological changes. It triggers apoptosis by constraining Bcl-2 and elevating caspase-3 levels. GTN also attenuated the P13K/AKT signaling which enhanced apoptosis. These findings revealed that GTN subdues the P13K/AKT pathway and has auspicious chemopreventive and apoptotic actions in DEN-induced HCC. Therefore, GTN would be suggested as a new medicine in natural remedies for liver cancer. [ABSTRACT FROM AUTHOR]

With high incidence of hepatocarcinoma and limited effective treatments, most patients suffer in pain. Antitumor drugs are single-targeted, toxicity, causing adverse side effects and resistance. Dihydroartemisinin (DHA) inhibits tumor through multiple mechanisms effectively. This study explores and evaluates safety and potential mechanism of DHA towards human hepatocarcinoma based on network pharmacology in a comprehensive way. Adsorption, distribution, metabolism, excretion, and toxicity (ADMET) properties of DHA were evaluated with pkCSM, SwissADME, and ADMETlab. Potential targets of DHA were obtained from SwissTargetPrediction, Drugbank, TargetNET, and PharmMapper. Target gene of hepatocarcinoma was obtained from OMIM, GeneCards, and DisGeNET. Overlapping targets and hub genes were identified and analyzed for Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Reactome pathway. Molecular docking was utilized to investigate the interactions sites and hydrogen bonds. Cell counting kit-8 (CCK8), wound healing, invasion, and migration assays on HepG2 and SNU387 cell proved DHA inhibits malignant biological features of hepatocarcinoma cell. DHA is safe and desirable for clinical application. A total of 131 overlapping targets were identified. Biofunction analysis showed targets were involved in kinase activity, protein phosphorylation, intracellular reception, signal transduction, transcriptome dysregulation, PPAR pathway, and JAK-STAT signaling axis. Top 9 hub genes were obtained using MCC (Maximal Clique Centrality) algorithm, namely CDK1, CCNA2, CCNB1, CCNB2, KIF11, CHEK1, TYMS, AURKA, and TOP2A. Molecular docking suggests that all hub genes form a stable interaction with DHA for optimal binding energy were all less than − 5 kcal/mol. Dihydroartemisinin might be a potent and safe anticarcinogen based on its biological safety and effective therapeutic effect. [ABSTRACT FROM AUTHOR]

Abstract Hepatocellular carcinoma (HCC) associated with viral or metabolic liver diseases is a growing cancer without effective therapy. AMPK is downregulated in HCC and its activation diminishes tumor growth. Alpha lipoic acid (ALA), an indirect AMPK activator that inhibits hepatic steatosis, shows antitumor effects in different cancers. We aimed to study its putative action in liver-cancer derived cell lines through AMPK signaling. We performed cytometric studies for apoptosis and cell cycle, and 2D and 3D migration analysis in HepG2/C3A and Hep3B cells. ALA led to significant inhibition of cell migration/invasion only in HepG2/C3A cells. We showed that these effects depended on AMPK, and ALA also increased the levels and nuclear compartmentalization of the AMPK target p53. The anti-invasive effect of ALA was abrogated in stable-silenced (shTP53) versus isogenic-TP53 HepG2/C3A cells. Furthermore, ALA inhibited epithelial-mesenchymal transition (EMT) in control HepG2/C3A but not in shTP53 nor in Hep3B cells. Besides, we spotted that in patients from the HCC-TCGA dataset some EMT genes showed different expression patterns or survival depending on TP53. ALA emerges as a potent activator of AMPK-p53 axis in HCC cells, and it decreases migration/invasion by reducing EMT which could mitigate the disease in wild-type TP53 patients.

Abstract Liver cancers, including hepatocellular carcinoma (HCC), are the sixth most common cancer and the third leading cause of cancer-related death worldwide, representing a global public health problem. This study evaluated nine patients with HCC. Six of the cases involved hepatic explants, and three involved hepatic segmentectomy for tumor resection. Eight out of nine tumors were HCC, with one being a combined hepatocellular-cholangiocarcinoma tumor. Conventional markers of hepatocellular differentiation (Hep Par-1, arginase, pCEA, and glutamine synthetase) were positive in all patients, while markers of hepatic precursor cells (CK19, CK7, EpCAM, and CD56) were negative in most patients, and when positive, they were detected in small, isolated foci. Based on in silico analysis of HCC tumors from The Cancer Genome Atlas database, we found that Hedgehog (HH) pathway components (GLI1, GLI2, GLI3 and GAS1) have high connectivity values (module membership > 0.7) and are strongly correlated with each other and with other genes in biologically relevant modules for HCC. We further validated this finding by analyzing the gene expression of HH components (PTCH1, GLI1, GLI2 and GLI3) in our samples through qPCR, as well as by immunohistochemical analysis. Additionally, we conducted a chemosensitivity analysis using primary HCC cultures treated with a panel of 18 drugs that affect the HH pathway and/or HCC. Most HCC samples were sensitive to sunitinib. Our results offer a comprehensive view of the molecular landscape of HCC, highlighting the significance of the HH pathway and providing insight into focused treatments for HCC.

Abstract Background The metabolic reprogramming of amino acids is critical for cancer cell growth and survival. Notably, intracellular accumulation of cysteine is often observed in various cancers, suggesting its potential role in alleviating the oxidative stress associated with rapid proliferation. The liver is the primary organ for cysteine biosynthesis, but much remains unknown about the metabolic alterations of cysteine and their mechanisms in hepatocellular carcinoma cells. Methods RNA-seq data from patients with hepatocarcinoma were analyzed using the TNMplot database. The underlying mechanism of the oncogenic alteration of cysteine metabolism was studied in mice implanted with BNL 1ME A.7 R.1 hepatocarcinoma. Results Database analysis of patients with hepatocellular carcinoma revealed that the expression of enzymes involved in de novo cysteine synthesis was down-regulated accompanying with increased expression of the cystine uptake transporter xCT. Similar alterations in gene expression have also been observed in a syngeneic mouse model of hepatocarcinoma. The enhanced expression of DNA methyltransferase in murine hepatocarcinoma cells caused methylation of the upstream regions of cysteine synthesis genes, thereby repressing their expression. Conversely, suppression of de novo cysteine synthesis in healthy liver cells induced xCT expression by up-regulating the oxidative-stress response factor NRF2, indicating that reduced de novo cysteine synthesis repulsively increases cystine uptake via enhanced xCT expression, leading to intracellular cysteine accumulation. Furthermore, the pharmacological inhibition of xCT activity decreased intracellular cysteine levels and suppressed hepatocarcinoma tumor growth in mice. Conclusions Our findings indicate an underlying mechanism of the oncogenic alteration of cysteine metabolism in hepatocarcinoma and highlight the efficacy of alteration of cysteine metabolism as a viable therapeutic target in cancer.

Hepatocellular carcinoma (HCC) associated with viral or metabolic liver diseases is a growing cancer without effective therapy. AMPK is downregulated in HCC and its activation diminishes tumor growth. Alpha lipoic acid (ALA), an indirect AMPK activator that inhibits hepatic steatosis, shows antitumor effects in different cancers. We aimed to study its putative action in liver-cancer derived cell lines through AMPK signaling. We performed cytometric studies for apoptosis and cell cycle, and 2D and 3D migration analysis in HepG2/C3A and Hep3B cells. ALA led to significant inhibition of cell migration/invasion only in HepG2/C3A cells. We showed that these effects depended on AMPK, and ALA also increased the levels and nuclear compartmentalization of the AMPK target p53. The anti-invasive effect of ALA was abrogated in stable-silenced (shTP53) versus isogenic-TP53 HepG2/C3A cells. Furthermore, ALA inhibited epithelial-mesenchymal transition (EMT) in control HepG2/C3A but not in shTP53 nor in Hep3B cells. Besides, we spotted that in patients from the HCC-TCGA dataset some EMT genes showed different expression patterns or survival depending on TP53. ALA emerges as a potent activator of AMPK-p53 axis in HCC cells, and it decreases migration/invasion by reducing EMT which could mitigate the disease in wild-type TP53 patients. [ABSTRACT FROM AUTHOR]

Copyright of Medicina (Buenos Aires) is the property of Medicina (Buenos Aires) and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: The metabolic reprogramming of amino acids is critical for cancer cell growth and survival. Notably, intracellular accumulation of cysteine is often observed in various cancers, suggesting its potential role in alleviating the oxidative stress associated with rapid proliferation. The liver is the primary organ for cysteine biosynthesis, but much remains unknown about the metabolic alterations of cysteine and their mechanisms in hepatocellular carcinoma cells. Methods: RNA-seq data from patients with hepatocarcinoma were analyzed using the TNMplot database. The underlying mechanism of the oncogenic alteration of cysteine metabolism was studied in mice implanted with BNL 1ME A.7 R.1 hepatocarcinoma. Results: Database analysis of patients with hepatocellular carcinoma revealed that the expression of enzymes involved in de novo cysteine synthesis was down-regulated accompanying with increased expression of the cystine uptake transporter xCT. Similar alterations in gene expression have also been observed in a syngeneic mouse model of hepatocarcinoma. The enhanced expression of DNA methyltransferase in murine hepatocarcinoma cells caused methylation of the upstream regions of cysteine synthesis genes, thereby repressing their expression. Conversely, suppression of de novo cysteine synthesis in healthy liver cells induced xCT expression by up-regulating the oxidative-stress response factor NRF2, indicating that reduced de novo cysteine synthesis repulsively increases cystine uptake via enhanced xCT expression, leading to intracellular cysteine accumulation. Furthermore, the pharmacological inhibition of xCT activity decreased intracellular cysteine levels and suppressed hepatocarcinoma tumor growth in mice. Conclusions: Our findings indicate an underlying mechanism of the oncogenic alteration of cysteine metabolism in hepatocarcinoma and highlight the efficacy of alteration of cysteine metabolism as a viable therapeutic target in cancer. [ABSTRACT FROM AUTHOR]

Simple Summary: Hepatocellular carcinoma (HCC) is the predominant form of primary liver cancer (about 85–90%). In the advanced stage of the disease, existing therapies cause toxic side effects and patients often develop chemoresistance. It is therefore important to identify new compounds with low toxicity that can be used in patients with compromised liver and advanced HCC. The objective of this research was to study the antitumoral activity of delta-tocotrienol, a natural compound derived from Vitamin E, on human hepatocarcinoma cell lines. This study supports the evidence that this compound exerts an antitumoral action activating the autophagic process, leading to cancer cell death. We believe that these data may provide a basis for considering delta-tocotrienol as a potential adjuvant therapy for the treatment of advanced HCC. (1) Hepatocellular carcinoma (HCC) is the predominant form of primary liver cancer. Surgical resection, tumor ablation, and liver transplantation are curative treatments indicated for early-stage HCC. The management of intermediate and advanced stages of pathology is based on the use of systemic therapies which often show important side effects. Vitamin E-derivative tocotrienols (TTs) play antitumoral properties in different tumors. Here, we analyzed the activity of delta-TT (δ-TT) on HCC human cell lines. (2) We analyzed the ability of δ-TT to trigger apoptosis, to induce oxidative stress, autophagy, and mitophagy in HepG2 cell line. We evaluated the correlation between the activation of autophagy with the ability of δ-TT to induce cell death. (3) The data obtained demonstrate that δ-TT exerts an antiproliferative and proapoptotic effect in HCC cells. Furthermore, δ-TT induces the release of mitochondrial ROS and causes a structural and functional alteration of the mitochondria compatible with a fission process. Finally, δ-TT triggers selective autophagy process removing dysfunctional mitochondria. Inhibition of autophagy reversed the cytotoxic action of δ-TT. (4) Our results demonstrate that δ-TT through the activation of autophagy could represent a potential new approach in the treatment of advanced HCC. [ABSTRACT FROM AUTHOR]

Introduction: Tyrosinemia type 1 is a rare disease with autosomal recessive inheritance, featuring various clinical manifestations. These may encompass acute neonatal liver failure, neonatal cholestatic syndrome, chronic hepatitis, cirrhosis, hepatocellular carcinoma, and, alternatively, kidney disorders like renal tubular acidosis, Fanconi syndrome, hypophosphatemic rickets, among other alterations. Diagnosis relies on detecting toxic metabolites in the blood and urine, ideally confirmed through molecular testing. Method: A consensus was reached with experts in the field of inborn errors of metabolism (EIM), including eight pediatric gastroenterologists, two EIM specialists, two geneticists, three pediatric nutritionists specialized in EIM, and a pediatric surgeon specializing in transplants. Six working groups were tasked with formulating statements and justifications, and 32 statements were anonymously voted on using the Likert scale and the Delphi method. The first virtual vote achieved an 80% consensus, with the remaining 20% determined in person. Results: The statements were categorized into epidemiology, clinical presentation, diagnosis, nutritional and medical treatment, and genetic counseling. Conclusions: This consensus serves as a valuable tool for primary care physicians, pediatricians, and pediatric gastroenterologists, aiding in the prompt diagnosis and treatment of this disease. Its impact on the morbidity and mortality of patients with tyrosinemia type 1 is substantial. [ABSTRACT FROM AUTHOR]

Copyright of Medicina (Buenos Aires) is the property of Medicina (Buenos Aires) and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background & Aims: Despite its growing incidence, hepatocellular carcinoma (HCC) related to metabolic dysfunction-associated steatotic liver disease (MASLD) in non-cirrhotic livers remains poorly characterized. We compared the characteristics, management, survival, and trends of MASLD-related HCC in patients with or without underlying cirrhosis in a large multicenter cohort. Methods: A total of 354 cases of MASLD-related HCC presented at the liver tumor meetings of four French university hospitals between 2007 and 2018 were included in the study. Data were extracted from the meetings’ databases and from the French Birth and Death Registry. Results: Of HCC cases, 35% occurred in the absence of cirrhosis. HCC was diagnosed through screening in 60% of patients with cirrhosis, and incidentally in 72% of patients without it. Patients without cirrhosis were older, had a greater tumor burden, but also better liver function than patients with cirrhosis. Patients without cirrhosis showed better overall survival than those with cirrhosis (p = 0.043). However, cirrhosis was not independently associated with overall survival, the independent predictors were age, liver function, tumor burden and BCLC classification. Patients without cirrhosis underwent surgery more frequently than patients with cirrhosis (41% vs. 11%, p

BACKGROUND: Malignant cells may arise from dedifferentiation of mature cells and acquire features of the progenitor cells. Definitive endoderm from which liver is derived, expresses glycosphingolipids (GSLs) such as stage-specific embryonic antigen 3 (SSEA3), Globo H, and stage-specific embryonic antigen 4 (SSEA4). Herein, we evaluated the potential prognosis value of the three GSLs and biological functions of SSEA3 in hepatocellular carcinoma (HCC). METHODS: The expression of SSEA3, Globo H, and SSEA4 in tumor tissues obtained from 328 patients with resectable HCC was examined by immunohistochemistry staining. Epithelial mesenchymal transition (EMT) and their related genes were analyzed by transwell assay and qRT-PCR, respectively. RESULTS: Kaplan Meier survival analysis showed significantly shorter relapse-free survival (RFS) for those with higher expression of SSEA3 (p

Activated platelets (PLT) could adhere to tumor cells to promote tumor progression and metastasis. Therefore, inhibiting platelet activation and blocking the interaction between tumor cells and platelets are an effective approach to inhibit distal tumor metastasis. In this study, chondroitin sulfate (CS)–glycyrrhetinic acid (GA) dual ligand-modified liposomes (CS–GA–LIP) were prepared for codelivery of aspirin (ASP) and curcumin (CUR). In order to simulate the tumor microenvironment, we established the "HuH-7 + PLT" in vitro coculture cell model and the "H22 + NIH/3T3" coinjected mice model. Physicochemical analysis showed that the particle size of CUR&ASP/CS–GA–LIP was 133.27 nm with high stability. In vitro studies found that CUR&ASP/CS–GA–LIP could target both hepatocellular carcinoma cells and platelets, enhance drug retention in tumor cells, and effectively inhibit tumor proliferation and migration. In addition, in vivo antitumor results demonstrated that CUR&ASP/CS–GA–LIP could aggregate in tumor tissues, inhibit platelet activation and neoangiogenesis, and down-regulate the expression of matrix metalloproteinase 2 (MMP-2), exhibiting strong antiproliferative and antipulmonary metastatic abilities. Consequently, the combination therapy based on CS–GA–LIP might be a valuable antihepatocellular carcinoma strategy. [ABSTRACT FROM AUTHOR]

Background: In recent years, many studies have attempted to develop models to predict the recurrence of hepatocarcinoma after liver transplantation. Method: A single-centre, retrospective cohort study analysed patients receiving transplants due to hepatocarcinoma during the 20 years of the transplant programme. We analysed patient survival, hepatocarcinoma recurrence and the influence of the different factors described in the literature as related to hepatocarcinoma recurrence. We compared the results of previous items between the first and second decades of the transplantation programme (1995–2010 and 2010–2020). Results: Of 265 patients, the patient survival rate was 68% at 5 years, 58% at 10 years, 45% at 15 years and 34% at 20 years. The overall recurrence rate of hepatocarcinoma was 14.5%, without differences between periods. Of these, 54% of recurrences occurred early, in the first two years after transplantation. Of the parameters analysed, an alpha-fetoprotein level of >16 ng/mL, the type of immunosuppression used and the characteristics of the pathological anatomy of the explant were significant. A trend towards statistical significance was identified for the number of nodules and the size of the largest nodule. Logistic regression analysis was used to develop a model with a sensitivity of 85.7% and a specificity of 35.7% to predict recurrences in our cohort. Regarding the comparison between periods, the survival and recurrence rates of hepatocarcinoma were similar. The impact of the factors analysed in both decades was similar. Conclusions: Most recurrences occur during the first two years post-transplantation, so closer follow-ups should be performed during this period, especially in those patients where the model predicts a high risk of recurrence. The detection of patients at higher risk of recurrence allows for closer follow-up and may, in the future, make them candidates for adjuvant or neoadjuvant systemic therapies to transplantation. [ABSTRACT FROM AUTHOR]

Non-alcoholic fatty liver disease (NAFLD) is a common chronic liver condition characterized by excess fat accumulation in the liver in the absence of significant alcohol consumption. While NAFLD itself is generally considered benign, it can progress to more severe forms such as non-alcoholic steatohepatitis, which can ultimately lead to liver cirrhosis and hepatocarcinoma, a type of liver cancer. The risk of developing hepatocarcinoma in individuals with NAFLD is considerably higher than in the general population. Factors such as obesity, diabetes, insulin resistance, and inflammation contribute to the development and progression of NAFLD and its subsequent transformation into hepatocarcinoma. Regular monitoring, lifestyle modifications, and timely treatment of co-existing conditions are crucial in mitigating the risk of hepatocarcinoma among patients with NAFLD. Further research into the underlying mechanisms linking NAFLD to hepatocarcinoma is essential for developing effective preventive strategies and treatments for this increasingly prevalent condition. [ABSTRACT FROM AUTHOR]

Over the past 10 years, the biological role of lipid droplets (LDs) has gained significant attention in the context of both physiological and pathological conditions. Considerable progress has been made in elucidating key aspects of these organelles, yet much remains to be accomplished to fully comprehend the myriad functions they serve in the progression of hepatic tumors. Our current perception is that LDs are complex and active structures managed by a distinct set of cellular processes. This understanding represents a significant paradigm shift from earlier perspectives. In this review, we aim to recapitulate the function of LDs within the liver, highlighting their pivotal role in the pathogenesis of metabolic dysfunction-associated steatotic liver disease (MASLD) (Hsu and Loomba, 2024) and their contribution to the progression towards more advanced pathological stages up to hepatocellular carcinoma (HC) (Farese and Walther, 2009). We are aware of the molecular complexity and changes occurring in the neoplastic evolution of the liver. Our attempt, however, is to summarize the most important and recent roles of LDs across both healthy and all pathological liver states, up to hepatocarcinoma. For more detailed insights, we direct readers to some of the many excellent reviews already available in the literature (Gluchowski et al., 2017; Hu et al., 2020; Seebacher et al., 2020; Paul et al., 2022). [ABSTRACT FROM AUTHOR]

Simple Summary: Liver transplantation is the gold standard treatment for hepatocarcinoma, and its outcome is strongly influenced by HCC staging. However, concordance between pre-LT radiological and definitive pathological staging remains controversial. The aim of our retrospective study was to assess concordance between radiology and pathology and to explore the factors associated with poor concordance and outcomes. We analyzed all LTs with an HCC diagnosis performed between 2013 and 2018. Concordance (Co group) was defined as a comparable tumor burden in preoperative imaging and post-transplant pathology; otherwise, non-concordance was diagnosed (nCo group). We confirmed the low concordance rate between the radiology and pathology staging systems. The concordance rate between the pre-LT imaging and histopathological results was lower in patients with a high number of nodules. Multiple bridging therapies reduce the accuracy of pre-LT imaging in predicting HCC stages and negatively affect outcomes after LT. The outcome of liver transplantation (LT) for hepatocarcinoma (HCC) is strongly influenced by HCC staging, which is based on radiological examinations in a pre-LT setting; concordance between pre-LT radiological and definitive pathological staging remains controversial. To address this issue, we retrospectively analyzed our LT series to assess concordance between radiology and pathology and to explore the factors associated with poor concordance and outcomes. We included all LTs with an HCC diagnosis performed between 2013 and 2018. Concordance (Co group) was defined as a comparable tumor burden in preoperative imaging and post-transplant pathology; otherwise, non-concordance was diagnosed (nCo group). Concordance between radiology and pathology was observed in 32/134 patients (Co group, 24%). The number and diameter of the nodules were higher when nCo was diagnosed, as was the number of pre-LT treatments. Although concordance did not affect survival, more than three pre-LT treatments led to a lower disease-free survival. Patients who met the Milan Criteria (Milan-in patients) were more likely to receive ≥three prior treatments, leading to a lower survival in multi-treated Milan-in patients than in other Milan-in patients. In conclusion, the concordance rate between the pre-LT imaging and histopathological results was low in patients with a high number of nodules. Multiple bridging therapies reduce the accuracy of pre-LT imaging in predicting HCC stages and negatively affect outcomes after LT. [ABSTRACT FROM AUTHOR]

Over-expression of glutathione S-transferase (GST) can promote Cisplatin resistance in hepatocellular carcinoma (HCC) treatment. Hence, inhibiting GST is an attractive strategy to improve Cisplatin sensitivity in HCC therapy. Although several synthesized GST inhibitors have been developed, the side effects and narrow spectrum for anticancer seriously limit their clinical application. Considering the abundance of natural compounds with anticancer activity, this study developed a rapid fluorescence technique to screen “green” natural GST inhibitors with high specificity. The fluorescence assay demonstrated that schisanlactone B (hereafter abbreviated as C1) isolated from Xue tong significantly down-regulated GST levels in Cisplatin-resistant HCC cells in vitro and in vivo. Importantly, C1 can selectively kill HCC cells from normal liver cells, effectively improving the therapeutic effect of Cisplatin on HCC mice by down-regulating GST expression. Considering the high GST levels in HCC patients, this compound demonstrated the high potential for sensitizing HCC therapy in clinical practice by down-regulating GST levels.

Over the past 10 years, the biological role of lipid droplets (LDs) has gained significant attention in the context of both physiological and pathological conditions. Considerable progress has been made in elucidating key aspects of these organelles, yet much remains to be accomplished to fully comprehend the myriad functions they serve in the progression of hepatic tumors. Our current perception is that LDs are complex and active structures managed by a distinct set of cellular processes. This understanding represents a significant paradigm shift from earlier perspectives. In this review, we aim to recapitulate the function of LDs within the liver, highlighting their pivotal role in the pathogenesis of metabolic dysfunction-associated steatotic liver disease (MASLD) (Hsu and Loomba, 2024) and their contribution to the progression towards more advanced pathological stages up to hepatocellular carcinoma (HC) (Farese and Walther, 2009). We are aware of the molecular complexity and changes occurring in the neoplastic evolution of the liver. Our attempt, however, is to summarize the most important and recent roles of LDs across both healthy and all pathological liver states, up to hepatocarcinoma. For more detailed insights, we direct readers to some of the many excellent reviews already available in the literature (Gluchowski et al., 2017; Hu et al., 2020; Seebacher et al., 2020; Paul et al., 2022).

Background: Malignant cells may arise from dedifferentiation of mature cells and acquire features of the progenitor cells. Definitive endoderm from which liver is derived, expresses glycosphingolipids (GSLs) such as stage-specific embryonic antigen 3 (SSEA3), Globo H, and stage-specific embryonic antigen 4 (SSEA4). Herein, we evaluated the potential prognosis value of the three GSLs and biological functions of SSEA3 in hepatocellular carcinoma (HCC). Methods: The expression of SSEA3, Globo H, and SSEA4 in tumor tissues obtained from 328 patients with resectable HCC was examined by immunohistochemistry staining. Epithelial mesenchymal transition (EMT) and their related genes were analyzed by transwell assay and qRT-PCR, respectively. Results: Kaplan Meier survival analysis showed significantly shorter relapse-free survival (RFS) for those with higher expression of SSEA3 (p

Hepatocellular carcinoma (HCC) is a common severe type of liver cancer characterized by an extremely aggressive course and low survival rates. It is known that disruptions in the regulation of apoptosis activation are some of the key features inherent in most cancer cells, which determines the pharmacological induction of apoptosis as an important strategy for cancer therapy. The computer design of chemical compounds capable of specifically regulating the external signaling pathway of apoptosis induction represents a promising approach for creating new effective ways of therapy for liver cancer and other oncological diseases. However, at present, most of the studies are devoted to pharmacological effects on the internal (mitochondrial) apoptosis pathway. In contrast, the external pathway induced via cell death receptors remains out of focus. Aberrant gene methylation, along with hepatitis C virus (HCV) infection, are important risk factors for the development of hepatocellular carcinoma. The reconstruction of gene networks describing the molecular mechanisms of interaction of aberrantly methylated genes with key participants of the extrinsic apoptosis pathway and their regulation by HCV proteins can provide important information when searching for pharmacological targets. In the present study, 13 criteria were proposed for prioritizing potential pharmacological targets for developing anti-hepatocarcinoma drugs modulating the extrinsic apoptosis pathway. The criteria are based on indicators of the structural and functional organization of reconstructed gene networks of hepatocarcinoma, the extrinsic apoptosis pathway, and regulatory pathways of virus-extrinsic apoptosis pathway interaction and aberrant gene methylation-extrinsic apoptosis pathway interaction using ANDSystem. The list of the top 100 gene targets ranked according to the prioritization rating was statistically significantly (p-value = 0.0002) enriched for known pharmacological targets approved by the FDA, indicating the correctness of the prioritization method. Among the promising potential pharmacological targets, six highly ranked genes (JUN, IL10, STAT3, MYC, TLR4, and KHDRBS1) are likely to deserve close attention.

An 82-year-old man with Philadelphia chromosome-negative acute lymphoblastic leukemia (ALL) complicated by hepatocarcinoma was presented. Remission induction therapy of hyper-CVAD with half dose reduction achieved hematological complete remission (CR), but accompanied with elevated alanine aminotransferase and hyperbilirubinemia. The patient was thought intolerable for hyper-CVAD with half dose reduction due to liver toxicity, and treatment was switched to blinatumomab. Hematological CR was sustained after nine cycles of blinatumomab without exacerbation of liver dysfunction. After five courses of blinatumomab, hepatocarcinoma was treated successfully by trans-arterial chemoembolization. Two years after the diagnosis of ALL, the patient was alive in CR status of ALL.

Gastrointestinal cancers are one of the most frequent cancers and a leading cause of cancer deaths worldwide. We provide an overview of the most important practice-changing trials that were either published or presented at the international scientific meetings in 2021–2023. Highlights included reports on three phase III trials (CONCORDE/PRODIGE 26, ARTDECO, and a study by Xu et al.) that evaluated dose escalation in the definitive setting for locally advanced oesophageal cancers, as well as two phase III trials that evaluated the role of chemotherapy (neo-AEGIS) and targeted therapy (NRG/RTOG 1010) in the neoadjuvant setting for adenocarcinoma oesophageal cancers or gastroesophageal junction cancer. CheckMate 577 evaluated nivolumab in patients who had residual pathological disease after neoadjuvant chemoradiation followed by complete resection. The use of radiation therapy for borderline and locally advanced pancreatic cancer is also discussed (SMART and CONKO-007 trials). Stereotactic body radiation therapy followed by sorafenib was compared to sorafenib alone in patients with hepatocellular carcinoma in the NRG/RTOG 1112 study. New options in the management of rectal cancer are emerging such as total neoadjuvant treatment (PRODIGE 23, RAPIDO, PROSPECT), organ preservation (OPRA, OPERA), and the role of immunotherapy in patients with DNA mismatch-repair deficient/microsatellite instability. Finally, preliminary results of the ACT 4 trial that evaluated de-escalation in anal cancer are presented. [ABSTRACT FROM AUTHOR]

Simple Summary: This research aimed to compare the outcomes of primary liver transplantation (PLT) and salvage liver transplantation (SLT) for hepatocellular carcinoma (HCC). The aim was to determine which approach offers better oncological outcomes and whether SLT after previous curative treatments such as liver resection (LR) or radiofrequency ablation (RFA) is as effective as PLT. Data analyzed from 141 patients who underwent liver transplantation for HCC found that PLT resulted in significantly longer disease-free survival, overall survival, and cancer-specific survival (CSS) compared to SLT. However, within the SLT group, there was no significant difference in DFS between SLT-LR and SLT-RFA. These findings suggest that PLT may provide superior long-term oncological outcomes, and a shift towards PLT rather than SLT may be worth considering. Further research is needed to confirm these results, but this study provides valuable insights for the research community regarding optimal transplantation strategies for HCC patients. Liver transplantation for hepatocellular carcinoma (HCC) may be performed ab initio, primary liver transplantation (PLT), or for HCC recurrence after previous treatments such as liver resection (LR) or radiofrequency ablation (RFA), salvage liver transplantation (SLT). The aim of this study was to evaluate the oncological outcomes of SLT vs. PLT. For this, a retrospective study was carried out on patients undergoing liver transplantation for HCC. The outcomes of PLT were compared with those of SLT. The primary outcome was disease-free survival (DFS). The secondary outcomes included overall survival (OS), cancer-specific survival (CSS), and major postoperative complications. A sub-analysis of SLT-LR and SLT-RFA was also performed. In total, 141 patients were included: 96 underwent PLT and 45 SLT. Among the SLT group, 25 patients had undergone previous LR while 20 had had RFA. There were no differences in the major postoperative complications. Unadjusted DFS was significantly longer in the PLT group (p = 0.02), as were OS (p = 0.025) and CSS (p = 0.001). There was no difference in DFS between PLT and SLT-LR groups, while a significant difference was found between the PLT and SLT-RFA groups (p = 0.035). Nonetheless, DFS was no different between the SLT-LR and SLT-RFA groups. PLT appears to offer superior long-term oncological outcomes to SLT. Both SLT-LR and SLT-RFA offer acceptable OS and CSS. Further prospective studies are needed to confirm these results, but the re-direction of grafts and transplant philosophy towards PLT rather than SLT may need to be considered. [ABSTRACT FROM AUTHOR]

Objective: To investigate the diagnostic value of early dynamic 18F-FDG PET/CT(ED 18F-FDG PET/CT) combined with conventional whole-body 18F-FDG PET/CT(WB 18F-FDG PET/CT) in hepatocellular carcinoma (HCC), as well as the difference of early dynamic blood flow parameters and maximum standardized uptake value (SUVmax) in HCC patients with/without liver cirrhosis or microvascular invasion (MVI). Methods: Twenty-two consecutive patients (mean age 57.8 years) with 28 established HCC lesions (mean size 4.5 cm) underwent a blood flow study with an 18F-FDG dynamic scan divided into 24 sequences of 5 s each and a standard PET/CT scan. On the ED PET/CT study, an experienced PET/CT physician obtained volumes of interest (VOIs) where three blood flow estimates (time to peak [TTP], blood flow [BF], and hepatic perfusion index [HPI]) were calculated. On the WB PET/CT study, a VOI was placed on the fused scan for each HCC and maximum standardized uptake value (SUVmax) was obtained. Comparison of blood flow estimates, SUVmax, and tumor/background ratio (TNR) was performed among HCCs with and without angioinvasion, as well as HCCs in cirrhotic and non-cirrhotic liver. Results: Compared with WB 18F-FDG PET/CT alone, ED combined with WB 18F-FDG PET/CT can significantly increase the detection rate of moderately differentiated and poorly differentiated HCCs (both P < 0.05). HPI was higher in HCCs in patients with liver cirrhosis than those without liver cirrhosis (P = 0.044). There was no significant difference in TTP, BF, SUVmax, or TNR between HCCs in patients with liver cirrhosis and those without liver cirrhosis. There was no significant difference in blood flow estimates or SUVmax in background liver parenchyma between patients with and those without cirrhosis. TTP was shorter in HCCs with MVI than without MVI (P = 0.046). There was no significant difference in BF, HPI, SUVmax, or TNR between HCCs with MVI and without MVI. There was no significant difference in blood flow estimates or SUVmax in background liver parenchyma between patients with and those without MVI. Conclusion: ED combined with WB 18F-FDG PET/CT can significantly increase the detection rate of moderately differentiated and poorly differentiated HCCs. HPI was significantly higher in HCCs in patients with liver cirrhosis than those without liver cirrhosis. TTP was significantly shorter in HCCs with MVI than without MVI. [ABSTRACT FROM AUTHOR]

Background: In recent years, many studies have attempted to develop models to predict the recurrence of hepatocarcinoma after liver transplantation. Method: A single-centre, retrospective cohort study analysed patients receiving transplants due to hepatocarcinoma during the 20 years of the transplant programme. We analysed patient survival, hepatocarcinoma recurrence and the influence of the different factors described in the literature as related to hepatocarcinoma recurrence. We compared the results of previous items between the first and second decades of the transplantation programme (1995–2010 and 2010–2020). Results: Of 265 patients, the patient survival rate was 68% at 5 years, 58% at 10 years, 45% at 15 years and 34% at 20 years. The overall recurrence rate of hepatocarcinoma was 14.5%, without differences between periods. Of these, 54% of recurrences occurred early, in the first two years after transplantation. Of the parameters analysed, an alpha-fetoprotein level of >16 ng/mL, the type of immunosuppression used and the characteristics of the pathological anatomy of the explant were significant. A trend towards statistical significance was identified for the number of nodules and the size of the largest nodule. Logistic regression analysis was used to develop a model with a sensitivity of 85.7% and a specificity of 35.7% to predict recurrences in our cohort. Regarding the comparison between periods, the survival and recurrence rates of hepatocarcinoma were similar. The impact of the factors analysed in both decades was similar. Conclusions: Most recurrences occur during the first two years post-transplantation, so closer follow-ups should be performed during this period, especially in those patients where the model predicts a high risk of recurrence. The detection of patients at higher risk of recurrence allows for closer follow-up and may, in the future, make them candidates for adjuvant or neoadjuvant systemic therapies to transplantation.

La incidencia del Hepatocarcinoma (HCC) se incrementó en los últimos años, también la presencia de HCC en pacientes con antecedentes de otros tumores es posible ya sea como tumores nuevos o de novo, por esta razón que hoy en día el tratamiento de estos pacientes está a cargo de un equipo multidisciplinario conformado por cirujanos de trasplante, hepatólogos, oncólogos, radiólogos. La incidencia de los pacientes con cirrosis que desarrollaron HCC es del 2 al 8%. Si bien es cierto la frecuencia es baja en pacientes que tienen otras patologías oncológicas se debe tener en cuenta la respuesta que tuvo el paciente con el primer tumor y al menos un periodo de tiempo mínimo de 2 años de estar libre de enfermedad para considerarse un HCC nuevo o de novo.

Herein, we investigated the effects of acetone precipitation on the bioactivity of blue-maize zein hydrolysates (BmapZDH) against hepatocarcinoma (HepG2) and non-tumor cells (fibroblasts). Zein proteins were extracted from blue-maize flour hydrolyzed with Alcalase for 6 h, and the peptide fractions were filtered (

The characteristics and fate of cancer cells partly depend on their environmental stiffness, i.e., the local mechanical cues they face. HepaRG progenitors are liver carcinoma cells exhibiting transdifferentiation properties; however, the underlying mechanisms remain unknown. To evaluate the impact of external physical forces mimicking the tumor microenvironment, we seeded them at very high density for 20 h, keeping the cells round and unanchored to the substrate. Applied without corticoids, spatial confinement due to very high density induced reprogramming of HepaRG cells into stable replicative stem-like cells after replating at normal density. Redifferentiation of these stem-like cells into cells very similar to the original HepaRG cells was then achieved using the same stress but in the presence of corticoids. This demonstrates that the cells retained the memory required to run the complete hepatic differentiation program, after bypassing the Hayflick limit twice. We show that physical stress improved chromosome quality and genomic stability, through greater efficiency of DNA repair and restoration of telomerase activity, thus enabling cells to escape progression to a more aggressive cancer state. We also show the primary importance of high-density seeding, possibly triggering compressive stress, in these processes, rather than that of cell roundness or intracellular tensional signals. The HepaRG-derived lines established here considerably extend the lifespan and availability of this surrogate cell system for mature human hepatocytes. External physical stress is a promising way to create a variety of cell lines, and it paves the way for the development of strategies to improve cancer prognosis. [ABSTRACT FROM AUTHOR]

Simple Summary: Non-alcoholic fatty liver disease (NAFLD) is a spectrum of disease ranging from simple steatosis (NAFL) to non-alcoholic steatohepatitis (NASH), which can progress to fibrosis and cirrhosis and ultimately lead to hepatocarcinoma (HCC). Due to its increasing prevalence, NAFLD has become a major public health problem. Given the partial understanding of the complex pathological mechanisms of NAFLD-induced human HCC and the lack of effective treatment, relevant pre-clinical models are still urgently needed to better recapitulate and investigate the process and mechanism of human NAFLD/HCC. This review discusses a selection of the most relevant mouse models in the study of NAFLD/HCC, with their specific advantages and disadvantages, and also the emergence of new ex vivo technologies, which will greatly accelerate the transition from basic science to clinical discoveries. Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer and one of the deadliest cancers worldwide. Despite extensive research, the biological mechanisms underlying HCC's development and progression remain only partially understood. Chronic overeating and/or sedentary-lifestyle-associated obesity, which promote Non-Alcoholic Fatty Liver Disease (NAFLD), have recently emerged as worrying risk factors for HCC. NAFLD is characterized by excessive hepatocellular lipid accumulation (steatosis) and affects one quarter of the world's population. Steatosis progresses in the more severe inflammatory form, Non-Alcoholic Steatohepatitis (NASH), potentially leading to HCC. The incidence of NASH is expected to increase by up to 56% over the next 10 years. Better diagnoses and the establishment of effective treatments for NAFLD and HCC will require improvements in our understanding of the fundamental mechanisms of the disease's development. This review describes the pathogenesis of NAFLD and the mechanisms underlying the transition from NAFL/NASH to HCC. We also discuss a selection of appropriate preclinical models of NAFLD for research, from cellular models such as liver-on-a-chip models to in vivo models, focusing particularly on mouse models of dietary NAFLD-HCC. [ABSTRACT FROM AUTHOR]

Para conocer los resultados de la radioembolización (transarterial radioembolization o TARE), en el tratamiento de tumores hepáticos, se realizó una valoración retrospectiva tras 112 TARE con 90Y-microesferas administradas en 82 pacientes en un único hospital, analizando la eficacia y la seguridad, tras un seguimiento mayor o igual a 1 año post-TARE en todos los pacientes, y evaluando la posible relación entre la respuesta al tratamiento y la supervivencia de los pacientes. Se administraron 57 TARE únicas y 55 TARE múltiples en pacientes con hepatocarcinoma (53), metástasis hepáticas (25) y colangiocarcinoma (4), con evaluación previa multidisciplinar clínica, angiográfica y gammagráfica (planar/SPECT/SPECT-TC con 99mTc-MAA), modelo multicompartimental (ecuaciones MIRD), valoración gammagráfica post-TARE (planar/SPECT/SPECT-TC), seguimiento clínico-radiológico, evaluación de respuesta tumoral (criterios mRECIST) y análisis (Kaplan Meier) de supervivencia libre de progresión (SLP) y supervivencia global (SG). La intención terapéutica fue paliativa (82%) y como puente a trasplante hepático/resección quirúrgica (17%). Se obtuvo respuesta (R), completa o parcial, en el 65,9% de los casos. Al año post-TARE estaban libres de progresión el 34,7% de los pacientes con R y 19,2% de los no R (p:0,003), con SG del 80% para los R y 37,5% para los no R (p:0,001). Las curvas de supervivencia mostraron mediana de SG de 18 meses (95% IC 15,7-20,3) para los R y 9 meses (95% IC 6,1-11,8) para los no R (p:0,03). Efectos secundarios leves (27,6%) y severos (5,3%) resueltos, sin mayor incidencia tras TARE múltiple. La TARE con 90Y-microesferas en pacientes adecuadamente seleccionados con tumores hepáticos, aporta eficacia terapéutica y bajo índice de toxicidad, con SLP y SG superiores en los pacientes con respuesta a la TARE respecto a los que no respondieron. To determine the results of radioembolization transarterial (TARE), in the treatment of liver tumors, a retrospective evaluation was performed after 112 TARE with 90Y-microspheres administered in 82 patients in a single hospital, analyzing efficacy and safety, after a follow-up greater than or equal to 1 year post-TARE in all patients, and evaluating the possible relationship between treatment response and patient survival. We have administered 57 single TARE and 55 multiple TARE in patients with hepatocellular carcinoma (53), liver metastases (25) and cholangiocarcinoma (4), with prior multidisciplinary evaluation, clinical, angiographic and gammagraphic (planar/SPECT/SPECT-CT with 99mTc-MAA), multicompartment model (MIRD equations), post-TARE screening (planar/SPECT/SPECT-CT), clinical and radiological follow-up, tumor response evaluation (mRECIST criteria) and Kaplan–Meier analysis to determine progression-free survival (PFS) and overall survival (OS). Therapeutic intention was palliative (82%) and as bridge to liver transplantation/surgical resection (17%). We obtained response (R), complete or partial, in 65.9% of cases. One year after TARE 34.7% of patients with R and 19.2% of non-R were progression-free (p : 0.003), with OS of 80% for R and 37.5% for non-R (p : 0.001). Survival analysis showed median OS of 18 months (95% CI 15.7–20.3) for R and 9 months (95% CI 6.1–11.8) for non-R (p : 0.03). We found mild (27.6%) and severe (5.3%) side effects, all of them resolved, without higher incidence after multiple TARE. TARE with 90Y-microspheres, in appropriately selected patients with liver tumors, provides therapeutic efficacy and low rate of toxicity, with higher PFS and OS in patients with TARE response compared to those who did not respond. [ABSTRACT FROM AUTHOR]

Copyright of Revista Médica de Risaralda is the property of Universidad Tecnologica de Pereira and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

It is estimated that 25% of the world's population has non-alcoholic fatty liver disease. This disease can advance to a more severe form, non-alcoholic steatohepatitis (NASH), a disease with a greater probability of progression to cirrhosis and hepatocellular carcinoma (HCC). NASH could be characterized as a necro-inflammatory complication of chronic hepatic steatosis. The combination of factors that lead to NASH and its progression to HCC in the setting of inflammation is not clearly understood. The portal vein is the main route of communication between the intestine and the liver. This allows the transfer of products derived from the intestine to the liver and the hepatic response pathway of bile and antibody secretion to the intestine. The intestinal microbiota performs a fundamental role in the regulation of immune function, but it can undergo changes that alter its functionality. These changes can also contribute to cancer by disrupting the immune system and causing chronic inflammation and immune dysfunction, both of which are implicated in cancer development. In this article, we address the link between inflammation, microbiota and HCC. We also review the different in vitro models, as well as recent clinical trials addressing liver cancer and microbiota. [ABSTRACT FROM AUTHOR]

All-trans retinoic acid (ATRA) can reverse the malignant behaviors of hepatocellular carcinoma (HCC) cells, thereby exerting anti-HCC effect; however, the underlying mechanism is yet to be understood. This study aimed to demonstrate that ATRA is vital to ferroptosis in HCC. Ferroptosis-related genes exhibit different expression in patients with HCC compared to that in healthy individuals. A total of 20 amino acid products were detected in HepG2 cells, the expression level of 5 was decreased after ATRA treatment. ATRA improved the levels of lipid ROS, MDA, and NAPD+/NADPH, and reduced the mt-DNA copy number and changed the structure of mitochondria, in HepG2 and Hep3B cells. We found the expression of genes positively correlated with ferroptosis to increase and those negatively correlated to decrease with ATRA treatment. Inhibition of ferroptosis by Ferrostatin-1 reversed ATRA-inhibited proliferation of HCC cells, along with cell migration and invasion. GSH synthesis was blocked by ATRA, accompanied by decreased cystine content and increased glutamate content, and downregulation of the expression of GSH synthesis-related genes. Our findings suggested that ATRA inhibited the malignancy of HCC cells by improving ferroptosis, and that inhibition of GSH synthesis contributed to ATRA-induced ferroptosis.

Background: Mushroom-derived components have immense potential to become a safe alternative in identifying lead anti-cancer molecules. Termitomyces heimii Natarajan (T. heimii) is a traditionally used edible mushroom with no previous record of anti-hepatocarcinoma activity. Methods: The anti-proliferative efficacy of the mushroom ethyl acetate extract was screened against a panel of seven cancer cell lines, namely Hep G2, MCF-7, MDA-MB-231, MAD-MB-436, MOLT-4, Reh, and K-562, and against peripheral blood mononuclear cells isolated from normal healthy donors by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide reduction assay. The impact of the extract on nuclear morphology was examined by 4′,6-diamidino-2-phenylindole staining and the apoptotic potential of the extract was evaluated through flow cytometry and Annexin V-PI dual staining, followed by an in vitro scratch assay to elucidate the anti-migratory potential of the extract. The apoptotic and anti-migratory effects were further validated using in silico molecular docking with four compounds, ergosterol, ergosta-5,8-dien-3-ol, lanosterol, and eburicol, against two anti-apoptotic proteins, Bcl-2 and Bcl-XL, and two angiogenic receptors, VEGFR-1 and VEGFR-2. Results: The screening data revealed that ethyl acetate extract exhibited remarkable anti-proliferative efficacy against Hep G2 cells, with a half maximal inhibitory concentration (IC50) value of 263.53 (8.09) μg/mL, followed by MCF-7 cell lines and showed a negligible effect on peripheral blood mononuclear cells. A clear alteration of the cellular and nuclear morphology was concentration-dependently observed in Hep G2 cells. The extract induced robust apoptosis and a significant concentration-dependent increase in the scratch area. The results of in silico docking revealed that compared to standard drug sunitinib, both ergosterol and ergosta-5,8-dien-3-ol displayed lower binding energy, and satisfactory drugability and absorption, distribution, metabolism, excretion, and toxicity properties. Conclusions: T. heimii is a potential source for isolating lead anticancer molecules in the future. Ergosterol and ergosta-5,8-dien-3-ol hold great promise as new drugs against hepatocarcinoma.

Objective: To explore the mechanism of Nauclea Officinalis of anti-liver cancer effect based on network pharmacology, and to preliminarily verify anti-liver cancer activity of Nauclea Officinalis through cell screening. Methods: Network pharmacology was used to screen for common targets of Nauclea Officinalis and liver cancer, protein-protein interaction (PPI) network was constructed, and enrichment analysis and mechanism prediction were conductd. Molecular docking of main active ingredients of Nauclea Officinalis with core targets was made. Preliminary verification was performed by in vitro cell experiments such as CCK8, cell apoptosis, and PCR. Results: After the screening, 14 active ingredients of Nauclea Officinalis were obtained, with 587 related targets. After mapping with liver cancer targets, there were 288 common targets, mainly including TP53, SRC, STAT3, and other core targets. Among them, compounds such as strictosamide, pumiloside and vincosamide may be potential active ingredients of Nauclea Officinalis of anti-liver cancer effect. They may participate in protein phosphorylation and negative regulation of the apoptosis process by mediating cancer pathways, PI3K/Akt and EGFR tyrosine kinase inhibitors resistance signaling pathways to play an anti-liver cancer role; molecular docking results showd that active ingredients of Nauclea Officinalis had a stable binding with liver cancer core targets; in vitro cell experiments showd that main ingredient strictosamide of Nauclea Officinalis had cytotoxicity against liver cancer cells, inhibited liver cancer cell proliferation (P<0.001), down-regulated gene expression of liver cancer HepG2 cells SRC, STAT3, MAPK3 (P<0.05), and induced liver cancer cell apoptosis (P<0.001). Conclusion: This study preliminarily explores the potential mechanism of active ingredients of Nauclea Officinalis against liver cancer and its preliminary pharmacological effects, providing a theoretical basis for the study of Nauclea Officinalis of anti-liver cancer mechanism. [ABSTRACT FROM AUTHOR]

Extracellular vesicles (EVs) are cell-derived membrane structures that are formed by budding from the plasma membrane or originate from the endosomal system. These microparticles (100 nm–100 µm) or nanoparticles (>100 nm) can transport complex cargos to other cells and, thus, provide communication and intercellular regulation. Various cells, such as hepatocytes, liver sinusoidal endothelial cells (LSECs) or hepatic stellate cells (HSCs), secrete and take up EVs in the healthy liver, and the amount, size and content of these vesicles are markedly altered under pathophysiological conditions. A comprehensive knowledge of the modified EV-related processes is very important, as they are of great value as biomarkers or therapeutic targets. In this review, we summarize the latest knowledge on hepatic EVs and the role they play in the homeostatic processes in the healthy liver. In addition, we discuss the characteristic changes of EVs and their potential exacerbating or ameliorating effects in certain liver diseases, such as non-alcoholic fatty liver disease (NAFLD), alcoholic fatty liver disease (AFLD), drug induced liver injury (DILI), autoimmune hepatitis (AIH), hepatocarcinoma (HCC) and viral hepatitis. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer, with high morbidity and mortality, which seriously threatens the health and life expectancy of patients. The traditional methods of treatment by surgical ablation, radiotherapy, chemotherapy, and more recently immunotherapy have not given the expected results in HCC. New integrative combined therapies, such as photothermal, photodynamic, photoimmune therapy (PTT, PDT, PIT), and smart multifunctional platforms loaded with nanodrugs were studied in this review as viable solutions in the synergistic nanomedicine of the future. The main aim was to reveal the latest findings and open additional avenues for accelerating the adoption of innovative approaches for the multi-target management of HCC. High-tech experimental medical applications in the molecular and cellular research of photosensitizers, novel light and laser energy delivery systems and the features of photomedicine integration via PDT, PTT and PIT in immuno-oncology, from bench to bedside, were introspected. Near-infrared PIT as a treatment of HCC has been developed over the past decade based on novel targeted molecules to selectively suppress cancer cells, overcome immune blocking barriers, initiate a cascade of helpful immune responses, and generate distant autoimmune responses that inhibit metastasis and recurrences, through high-tech and intelligent real-time monitoring. The process of putting into effect new targeted molecules and the intelligent, multifunctional solutions for therapy will bring patients new hope for a longer life or even a cure, and the fulfillment of the myth of Prometheus. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma is the most common primary malignant hepatic tumor and occurs most often in the setting of chronic liver disease. Liver transplantation is a curative treatment option and is an ideal solution because it solves the chronic underlying liver disorder while removing the malignant lesion. However, due to organ shortages, this treatment can only be applied to carefully selected patients according to clinical guidelines. Artificial intelligence is an emerging technology with multiple applications in medicine with a predilection for domains that work with medical imaging, like radiology. With the help of these technologies, laborious tasks can be automated, and new lesion imaging criteria can be developed based on pixel-level analysis. Our objectives are to review the developing AI applications that could be implemented to better stratify liver transplant candidates. The papers analysed applied AI for liver segmentation, evaluation of steatosis, sarcopenia assessment, lesion detection, segmentation, and characterization. A liver transplant is an optimal treatment for patients with hepatocellular carcinoma in the setting of chronic liver disease. Furthermore, AI could provide solutions for improving the management of liver transplant candidates to improve survival. [ABSTRACT FROM AUTHOR]

The present study aimed to identify a safe and effective non-oncology drug cocktail as an alternative to toxic chemotherapeutics for hepatocellular carcinoma (HCC) treatment. The assessment of cytotoxicity of cocktail (as co-adjuvant) in combination with chemotherapeutic docetaxel (DTX) is also aimed. Further, we aimed to develop an oral solid self-emulsifying drug delivery system (S-SEDDS) for the simultaneous delivery of identified drugs. The identified non-oncology drug cocktail could overcome the shortage of anticancer therapeutics and help to reduce cancer-related mortality. Moreover, the developed S-SEDDS could be an ideal system for concurrent oral delivery of non-oncology drug combinations. The non-oncology drugs (alone and in combinations) were screened in vitro for anticancer effect (against HepG2 cells) using (3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide; MTT) dye assay, and cell cycle arresting and apoptotic behaviors using the fluorescence-activated cell sorting (FACS) technique. The S-SEDDS is composed of drugs such as ketoconazole (KCZ), disulfiram (DSR), tadalafil (TLF), and excipients like span-80, tween-80, soybean oil, Leciva S-95, Poloxamer F108 (PF-108), and Neusilin® US2 (adsorbent carrier), which was developed and characterized. The cocktail composed of KCZ, DSR, and TLF has showed substantial cytotoxicity (at the lowest concentration of 3.3 pmol), HepG2 cell arrest at G0/G1 and S phases, and substantial cell death via apoptosis. The DTX inclusion into this cocktail has further resulted in increased cytotoxicity, cell arrest at the G2/M phase, and cell necrosis. The optimized blank liquid SEDDS that remains transparent without phase separation for more than 6 months is used for the preparation of drug-loaded liquid SEDDS (DL-SEDDS). The optimized DL-SEDDS with low viscosity, good dispersibility, considerable drug retention upon dilution, and smaller particle size is further converted into drug-loaded solid SEDDS (DS-SEDDS). The final DS-SEDDS demonstrated acceptable flowability and compression characteristics, significant drug retention (more than 93%), particle size in nano range (less than 500 nm), and nearly spherical morphology following dilutions. The DS-SEDDS showed substantially increased cytotoxicity and Caco-2 cell permeability than plain drugs. Furthermore, DS-SEDDS containing only non-oncology drugs caused lower in vivo toxicity (only 6% body weight loss) than DS-SEDDS containing non-oncology drugs with DTX (about 10% weight loss). The current study revealed a non-oncology drug combination effective against HCC. Further, it is concluded that the developed S-SEDDS containing non-oncology drug combination alone and in combination with DTX could be a promising alternative to toxic chemotherapeutics for the effective oral treatment of hepatic cancer. [ABSTRACT FROM AUTHOR]

Copyright of Nouveau Praticien Vétérinaire Canine & Féline is the property of EDP Sciences and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

O autor procedeu a uma revisão sobre Marcadores Tumorais em Gastrenterologia. O relato enfatiza a utilidade e relatividade dessa metodologia quanto ao diagnóstico e prognóstico de alguns neoplasmas malignos (especialmente: carcinoma hepatocelular, adenocarcinoma de pâncreas e do cólon) do tracto digestivo. Outrossim, tais marcadores adquirem valor proeminente sobremaneira entre os grupos-de-risco conhecidos (entre os quais: cirróticos e portadores de hepatite crônica ativa ou do vírus B); nestes grupos, dentre outros métodos, eventualmente a dosagem de AFP, por exemplo, podería ser muito importante quanto ao rastreamento do CMC. Marcadores recém-desenvolvidos a partir de anticorpos monoclonais, atualmente em Investigação, são igualmente objeto de análise.

Abstract Introduction Despite the effectiveness of new therapies and awareness campaigns, the number of seropositive patients is increasing every year. Recently, other causes of death, not directly related to HIV, have emerged, such as chronic liver disease. The risk of hepatocellular carcinoma (HCC) is seven times greater in HIV patients than in noninfected patients, and it is especially attributable to HCV infection. The aim of our study was to evaluate clinical outcomes of HCC in HIV-HCV co-infected patients after liver resection (LR). Materials and methods The current study was conducted on a prospective database and reviewed retrospectively. All consecutive patients with HCC treated by LR from January 2013 to March 2019 at the Luigi Sacco University Hospital in Milan were enrolled. We included patients older than 18 years of age with HCV-related HCC, and in this set of patients, we identified two groups based on the presence of HIV infection. Results We identified 16 patients with HCV infection and precisely five with HIV-HCV co-infection and eleven with HCV infection alone. All HIV patients were male against 72.7% in the non-HIV group (p = 0.509). All patients had optimal HIV virologic control and a normal CD4 T-cell count. The mean diagnosis-to-treatment interval was statistically different between the two groups (HIV versus non-HIV: 1.2 ± 0.55 months versus 2.39 ± 1.09 months, p = 0.039). No other significant differences were found between HIV-HCV co-infected patients and HCV-infected patients. Long-term outcomes in terms of OS and RFS were similar between the two groups. Conclusions With a multidisciplinary approach and intensive support, LR can be a safe and efficacious procedure in HIV-HCV patients. For these reasons, we should not exclude potential patients merely on the basis of their HIV seropositivity.

ScopePrunus avium fruit is the richer source of phenolics known to exert anticancer and anti-invasive activities. The study aimed at elucidating antiproliferative and chemo-preventive potential of sweet cherries (P. avium) against the in vivo hepatocarcinoma model.Methods and resultsThe quantification of ultrasound-assisted extract (UAE) of P. avium depicted anthocyanins, ferulic acid, gallic acid, quercetin, syringic acid and p- and m-coumaric acids as major phytochemicals. The hepatocarcinoma (HCC) was induced in rats through intraperitoneal administration of DMBA (20 mg/kg B.W) once a week for the period of eight weeks. The intragastric administration of P. avium UAE, as cotreatment (500 mg/Kg B.W) to treatment group, significantly (p

Background: Contrast-enhanced ultrasound (CEUS) is an important imaging modality in the diagnosis of liver tumors. By using contrast agent, a more detailed image is obtained. Time-intensity curves (TIC) can be extracted using a specialized software, and then the signal can be analyzed for further investigations. Methods: The purpose of the study was to build an automated method for extracting TICs and classifying liver lesions in CEUS liver investigations. The cohort contained 50 anonymized video investigations from 49 patients. Besides the CEUS investigations, clinical data from the patients were provided. A method comprising three modules was proposed. The first module, a lesion segmentation deep learning (DL) model, handled the prediction of masks frame-by-frame (region of interest). The second module performed dilation on the mask, and after applying colormap to the image, it extracted the TIC and the parameters from the TIC (area under the curve, time to peak, mean transit time, and maximum intensity). The third module, a feed-forward neural network, predicted the final diagnosis. It was trained on the TIC parameters extracted by the second model, together with other data: gender, age, hepatitis history, and cirrhosis history. Results: For the feed-forward classifier, five classes were chosen: hepatocarcinoma, metastasis, other malignant lesions, hemangioma, and other benign lesions. Being a multiclass classifier, appropriate performance metrics were observed: categorical accuracy, F1 micro, F1 macro, and Matthews correlation coefficient. The results showed that due to class imbalance, in some cases, the classifier was not able to predict with high accuracy a specific lesion from the minority classes. However, on the majority classes, the classifier can predict the lesion type with high accuracy. Conclusions: The main goal of the study was to develop an automated method of classifying liver lesions in CEUS video investigations. Being modular, the system can be a useful tool for gastroenterologists or medical students: either as a second opinion system or a tool to automatically extract TICs. [ABSTRACT FROM AUTHOR]

Aim: To determine the correlation between the ADC values of liver lesions with the final results by imaging and histopathology. Material and methods: Non-probabilistic, retrospective, observational and cross-sectional study in the 2016-2019 period at Hospital Médica Sur, with 40 patients, affected liver segments. Diagnostic imaging and histopathology were evaluated, central tendency measures were used, percentages, as well as sensitivity, specificity and positive and negative predictive values. Results: 73 lesions were analyzed in 40 patients (21 women and 19 men) with an average age of 57.9 years; 69 of the 73 had an adequate diagnosis and only 4 different by biopsy. Segment VI was the most affected with 17 injuries, followed by V and VIII with 16 injuries. The lesions with the highest ADC value were hemangioma (1,711.18 x10-6 mm2/s), focal nodular hyperplasia (1,236.3 x10-6 mm2/s), and cholangitis (1,241 x10-6 mm2/s); with intermediate values liver adenoma (1,140 x10-6 mm2/s); the lesions that presented lower values were hepatocarcinoma (with values up to 479 x10-6 mm2/s), and cholangiocarcinoma (772.3 x10-6 mm2/s); the metastases showed fluctuating values from 800 x10-6 mm2/s to even 2,000 x10-6 mm2/s. Conclusions: An important correlation was found between the value of the ADC and the degree of malignancy of the lesions, however, the metastases presented variability in their value. The results are similar to the current literature, the results less than 1,000 x10-6 mm2/s correspond to potentially malignant lesions and those with an ADC value greater than 1,400 x10-6 mm2/s probably benign. [ABSTRACT FROM AUTHOR]