Explore the vast range of titles available.

Sirtuins (SIRT), first described as nicotinamide adenine dinucleotide (NAD + )-dependent type III histone deacetylases, are produced by cells to support in the defense against chronic stress conditions such as metabolic syndromes, neurodegeneration, and cancer. SIRT-3 is one of the most studied members of the mitochondrial sirtuins family. In particular, its involvement in metabolic diseases and its dual role in cancer have been described. In the present review, based on the evidence of SIRT-3 involvement in metabolic dysfunctions, we aimed to provide an insight into the multifaceted role of SIRT-3 in many solid and hematological tumors with a particular focus on hepatocellular carcinoma (HCC). SIRT-3 regulatory effect and involvement in metabolism dysfunctions may have strong implications in HCC development and treatment. Research literature widely reports the relationship between metabolic disorders and HCC development. This evidence suggests a putative bridge role of SIRT-3 between metabolic diseases and HCC. However, further studies are necessary to demonstrate such interconnection.

Background Post hoc analyses assessed the prognostic and predictive value of baseline alpha-fetoprotein (AFP), as well as clinical outcomes by AFP response or progression, during treatment in two placebo-controlled trials (REACH, REACH-2). Methods Serum AFP was measured at baseline and every three cycles. The prognostic and predictive value of baseline AFP was assessed by Cox regression models and Subpopulation Treatment Effect Pattern Plot method. Associations between AFP (≥ 20% increase) and radiographic progression and efficacy were assessed. Results Baseline AFP was confirmed as a continuous (REACH, REACH-2; p  < 0.0001) and dichotomous (≥400 vs. <400 ng/ml; REACH, p  < 0.01) prognostic factor, and was predictive for ramucirumab survival benefit in REACH ( p  = 0.0042 continuous; p  < 0.0001 dichotomous). Time to AFP (hazard ratio [HR] 0.513; p  < 0.0001) and radiographic (HR 0.549; p  < 0.0001) progression favoured ramucirumab. Association between AFP and radiographic progression was shown for up to 6 (odds ratio [OR] 5.1; p  < 0.0001) and 6–12 weeks (OR 1.8; p  = 0.0065). AFP response was higher with ramucirumab vs. placebo ( p  < 0.0001). Survival was longer in patients with an AFP response than patients without (13.6 vs. 5.6 months, HR 0.451; 95% confidence interval, 0.354–0.574; p  < 0.0001). Conclusions AFP is an important prognostic factor and a predictive biomarker for ramucirumab survival benefit. AFP ≥ 400 ng/ml is an appropriate selection criterion for ramucirumab. Clinical Trial Registration ClinicalTrials.gov, REACH (NCT01140347) and REACH-2 (NCT02435433).

Background Liver cancer stem cells (LCSCs) play key roles in the metastasis, recurrence, and chemotherapeutic resistance of hepatocellular carcinoma (HCC). Our previous research showed that the POSTN gene is closely related to the malignant progression and poor prognosis of HCC. This study aimed to elucidate the role of POSTN in generating LCSCs and maintaining their stemness as well as the underlying mechanisms. Methods Human HCC tissues and matched adjacent normal tissues were obtained from 110 patients. Immunohistochemistry, western blotting (WB), and RT-PCR were performed to detect the expression of POSTN and stemness factors. The roles of transforming growth factor (TGF)-β1 and AP-2α in the POSTN-induced stemness transformation of HCC cells were explored in vitro and in vivo using LCSCs obtained by CD133 + cell sorting. Results The high expression of POSTN was correlated with the expression of various stemness factors, particularly CD133, in our HCC patient cohort and in TCGA and ICGC datasets. Knockdown of POSTN expression decreased the abilities of HCC cell lines to form tumours in xenograft mouse models. Knockdown of POSTN expression also suppressed cell viability and clone formation, invasion, and sphere formation abilities in vitro. Knockdown of AP-2α attenuated the generation of CD133 + LCSCs and their malignant behaviours, indicating that AP-2α was a critical factor that mediated the POSTN-induced stemness transformation and maintenance of HCC cells. The role of AP-2α was verified by using a specific αvβ3 antagonist, cilengitide, in vitro and in vivo. Activation of POSTN could release TGFβ1 from the extracellular matrix and initiated POSTN/TGFβ1 positive feedback signalling. Furthermore, we found that the combined use of cilengitide and lenvatinib suppressed the growth of HCC cells with high POSTN expression more effectively than the use of lenvatinib alone in the patient-derived xenograft (PDX) mouse model. Conclusions The POSTN/TGFβ1 positive feedback pathway regulates the expression of stemness factors and the malignant progression of HCC cells by regulating the transcriptional activation of AP-2α. This pathway may serve as a new target for targeted gene therapy in HCC.

Maintenance of liver function is important for better outcomes after radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC). The aim of this study was to examine the effects of oral branched-chain amino acid (BCAA) supplementation on liver function, intrahepatic recurrence rate, and incidence of complications after RFA for HCC. Patients with cirrhosis who underwent RFA were enrolled between August 2009 and April 2012, randomized to oral supplementation with Aminoleban EN (BCAA group) or diet alone (control group), and followed to determine changes in serum parameters and health status. Patients in the BCAA group were instructed to ingest a packet of Aminoleban EN twice daily. Levels of physical and mental stress were assessed using the Short Form-8 health survey. Oral BCAA and dietary interventions were initiated 2 wk before local therapy, and contrast-enhanced computed tomography was performed every 3 mo to assess recurrence. We evaluated 25 patients in the BCAA group and 26 in the control group. The median follow-up period was 3.9 y (736–1818 d). There were no significant differences between the two groups in basal characteristics. Complications were less frequent in the BCAA group (P = 0.03). Event-free survival was significantly higher in the BCAA group, whereas the intrahepatic recurrence rate was significantly lower (P = 0.04 and 0.036, respectively). A significant improvement in the Short Form-8 mental component score was observed in the BCAA group only (P < 0.01). Aminoleban EN may be beneficial for cirrhotic patients after RFA to relieve mental stress and reduce the risks for intrahepatic recurrence and complications. •To our knowledge, this is the first prospective trial to verify the benefits of early-stage branched-chain amino acid (BCAA) supplementation during therapy for liver cirrhosis.•After radiofrequency ablation, Aminoleban EN may be beneficial for relieving mental stress.•BCAA administration can have a long-term inhibiting effect on carcinogenesis and can improve event-free and overall survival.

Objective Our study was to investigate the impact of taurolactone, a novel anti-tumor and anti-angiogenic drug, on AGGF1, an angiogenic factor, and angiogenesis mimicry in patients diagnosed with hepatocellular carcinoma (HCC). Methods A total of 120 HCC patients were enrolled from the Department of Oncology and Hepatobiliary Surgery at our hospital between May 2021 and December 2022. HCC diagnoses were confirmed through imaging or tissue biopsy for all patients. The age of patients ranged from 37 to 72 years, with an average age of 64.29 ± 4.58 years. These participants were divided equally into two groups: the control group and the observation group, each consisting of 60 individuals. While the control group received standard drug treatment, the observation group was administered taurolactone treatment. Before being included in the study, all participants or their legal representatives provided signed informed consent. Patient demographic information was collected through a questionnaire survey. ELISA was used to measure the levels of VEGF and AGGF1 in patients following treatment. Western blot was applied to assess the protein expression of PDGF, Angiopoietin, and AGGF1. MRI imaging technology was utilized to assess the perfusion characteristics of tumor blood vessels in patients. Tumor vessel density was compared between patients using ultrasonography. We also conducted a comparison between the two groups in terms of progression-free survival and overall survival. Results General patient information between the two groups showed no significant differences ( P  > 0.05). Of note, the observation group exhibited greatly lower levels of VEGF and AGGF1 compared to the control group ( P  < 0.05). Moreover, the levels of PDGF, Angiopoietin, and AGGF1 protein expression were significantly reduced in the observation group compared to the control group ( P  < 0.05). In terms of tumor perfusion, the observation group displayed lower average and maximum perfusion volumes in tumor blood vessels compared to the control group ( P  < 0.05). Additionally, the observation group demonstrated delayed peak times and arrival times of tumor blood vessels in comparison to the control group ( P  < 0.05). Furthermore, the density of tumor blood vessels was notably lower in the observation group compared to the control group ( P  < 0.05). Patients in the observation group had longer progression-free survival and overall survival than the control group ( P  < 0.05). Conclusion In HCC patients, our study highlighted the potential efficacy of taurolactone treatment as it effectively inhibited angiogenic factors and angiogenesis mimicry, ultimately leading to an improved prognosis for these patients.

Objective To investigate clinical effects of hepatic artery interventional embolization chemotherapy (TACE) for primary hepatocellular carcinoma (PHC). Methods 73 patients with PHC in our hospital from January 2017 to January 2018 were selected and divided into 37 cases in study group and 36 cases in control group by random number table method. The control group received only ultrasound-guided microwave ablation treatment, and the study group received TACE treatment again before surgery based on control group. The expression levels of cancer antigen 125 (CA125), alpha-fetoprotein (AFP), multiple tumor suppressors 1 (P16) proteins, and cancer antigen 19-9 (CA19-9) were compared between the two groups at different time periods after treatment, and the remission rate (ORR), control rate (DCR), complication rate at 3 months after treatment and survival rate at 3 years after treatment were compared. Results After 1 year of treatment, ORR, DCR, and P16 protein levels in the study group were higher than those in the control group ( P  < 0.05), and differences were statistically significant; CA125, CA19-9, and AFP levels in study group were lower than those in the control group ( P  < 0.05), and differences were statistically significant. The regression equation showed that long-term survival rate of both groups showed decreasing trend over time, while long-term survival rate of study group was always higher than that of the control group. Conclusion Comprehensive intervention for hepatic artery interventional chemoembolization in patients with primary hepatocellular carcinoma is more effective, which can effectively reduce incidence of complications and adverse effects in patients and help shorten treatment time of hepatic artery interventional chemoembolization in patients.

Background Biannual ultrasound (US)—with or without alpha-fetoprotein (AFP)—is recommended by current guidelines for the surveillance of hepatocellular carcinoma (HCC). However, the inadequate sensitivity of US has been a concern. Magnetic resonance imaging (MRI) is known to have high sensitivity in detecting hepatic malignancies, even without contrast enhancement. The purpose of our study is to compare US with noncontrast (unenhanced) MRI for HCC surveillance of high-risk patients. Methods/design MIRACLE-HCC (usefulness of noncontrast MagnetIc Resonance imAging versus nonContrast ultrasonography for surveiLlancE of HepatoCellular Carcinoma) is a prospective, single-center, nonblinded, balanced-randomized, parallel-group study. This study was approved by our institutional review board, and informed consent will be obtained from all participating patients. All patients with compensated liver cirrhosis will undergo noncontrast US or MRI, with serum AFP testing every 6 months. If a suspicious lesion is newly detected, or if the serum AFP level is elevated in an increasing trend for two consecutive tests, dynamic contrast-enhanced imaging will be performed to confirm the diagnosis. The primary endpoints are detection rates of very early or early stage HCC, stage distribution at the initial diagnosis, and false positive referral rates, which will be compared using Fisher’s exact or chi-square tests. The study will include 416 patients in a tertiary academic medical center in South Korea. Discussion MIRACLE-HCC is the first prospective randomized trial to compare the effectiveness of noncontrast MRI and noncontrast US in the surveillance of HCC in at-risk patients. The results of this trial will show whether noncontrast MRI surveillance is superior to noncontrast US surveillance in the early detection of HCC. The trial will also determine whether there are fewer false referrals with noncontrast MRI than with noncontrast US and, eventually, whether there is improvement in the overall survival of HCC patients. Trial registration The date of trial registration (ClincalTrials.gov: NCT02514434 ) for this study is July 23, 2015. Enrollment of participants was finished in November 2017. No authors have relationships, conditions, or circumstances that present potential conflicts of interest.

Background Gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid (Gd-EOB-DTPA) is an MRI contrast agent with perfusion and hepatoselective properties. The purpose of the study was to examine uptake of Gd-EOB-DTPA in the hepatobiliary phase in hepatocellular carcinoma (HCC). Methods A retrospective analysis of 22 patients with HCC who underwent preoperative Gd-EOB-DTPA-enhanced MRI was performed. Enhancement ratios (ERs) and expression levels of the organic anion transporter (OATP) 1B3 protein were examined. Results Gd-EOB-DTPA accumulated in the hepatobiliary phase in 6 of the 22 cases. All 6 Gd-EOB-DTPA-positive cases were moderately differentiated HCC, but 11 other moderately differentiated HCCs did not show Gd-EOB-DTPA uptake. Histopathologically, 4 Gd-EOB-DTPA-positive HCCs and 5 Gd-EOB-DTPA-negative HCCs produced bile. HCCs with Gd-EOB-DTPA uptake overexpressed OATP1B3 compared with HCCs without Gd-EOB-DTPA uptake, and OATP1B3 levels were significantly correlated with ERs (r = 0.91, P < 0.0001). Conclusions Uptake of Gd-EOB-DTPA in HCC is determined by expression of OATP1B3 rather than by tumor differentiation or bile production.

Background To develop and validate nomograms that can be used to predict outcomes in individuals suffering alpha‐fetoprotein (AFP) negative hepatocellular carcinoma (HCC) after radical resection. Methods A total of 509 AFP‐negative HCC patients who received hepatectomy between January 2009 and March 2013 in our center were randomized into training and validation cohorts. Nomograms for both overall and recurrence‐free survival (OS and RFS, respectively) were established based on the predictors in the training cohort. Nomograms performance and discriminative power were assessed with concordance index (C‐index) values and decision curve analyses (DCA). The results were validated in the validation cohort. Results Alkaline phosphatase, liver cirrhosis, tumor size, satellite lesions, microvascular invasion, and Edmondson‐Steiner grade were significantly linked to OS and RFS. Sex and tumor number were additional predictors for RFS. The OS nomogram had a C‐index value of 0.742, which was better than that for the AJCC eighth edition (0.632), BCLC system (0.553), and JIS score (0.557) (all P < .001). The RFS nomogram C‐index was 0.669, which was also superior to that of the AJCC eighth (0.608), BCLC stage (0.554), JIS score (0.551), and model of Gan et al (0.636) (P < .05 for all). Calibration curves indicated a good agreement between observed actual outcomes and predicted values. Kaplan‐Meier curves and DCA indicated that nomograms were powerful in discrimination and clinical usefulness. These results were supported by the validation cohort. Conclusions These nomograms presented more accurate prognostic prediction in patients with AFP‐negative HCC after hepatectomy. About 30% of HCC patients showed negative serum AFP and had special clinicopathologic characteristics and prognosis. We developed and validated nomograms for predicting prognosis of patients with AFP‐negative HCC after radical resection. Our novel nomograms presented superior performance and discrimination ability than conventional staging systems based on the C‐indexes, calibration curves, decision curve analysis and Kaplan‐Meier curves, which were proposed for clinical decision.

Background It is supposed that the improvement of prognosis in hepatocellular carcinoma (HCC) patient by anterior approach for liver resection was related to the decreasing hematogenic dissemination of circulating cancer cells. Methods The EpCAM + circulating tumor cells (CTCs) were detected in HCC patients having liver resection with either anterior approach (AA) or conventional approach (CA). The relation of CTCs to the 2-year recurrence and survival after surgery was investigated. Results Overall, patients with ≥3.5 CTCs had much higher recurrence rate than those with <3.5 CTCs (62.0 vs. 18.0%, P  = 0.001). Less CTCs were detected in AA group than that in CA group (mean, 2.1 vs. 3.0; median, 1.2 vs. 3.5; all P  = 0.001). The 2-year recurrence rate in AA group was much lower than in CA group (27.1 vs. 44.9%, P  = 0.009). The 2-year survival rate in AA group was much higher than in CA group (83.3 vs. 66.7%, P  = 0.001). The CTCs in >5 cm AA group were much less than that in >5 cm CA group (3.7 vs. 2.4, P  = 0.002). Moreover, the 2-year recurrence rate in >5 cm AA group was much lower than that in >5 cm CA group (29.2 vs. 54.7%, P  = 0.001). Also, the 2-year survival rates in >5 cm AA group were much higher than that in >5 cm CA group (72.9 vs. 49.1%, P  = 0.01). By multivariate analysis, CA is one of the independent risk factors for poor prognosis in HCC patients after liver resection. Conclusions Like the liver-directed therapies, AA can reduce the dissemination of CTCs, especially in patients with large-size HCC (>5 cm) and successively improve the early prognosis.