Hepatocellular Carcinoma In Clinical Practice Research Articles

Improved handling of BCLC 2022 update in the management of hepatocellular carcinoma in clinical practice

Improved handling of BCLC 2022 update in the management of hepatocellular carcinoma in clinical practice

Injectable Hydrogels Including Magnetic Nanosheets for Multidisciplinary Treatment of Hepatocellular Carcinoma via Magnetic Hyperthermia.

Relapse and unresectability have become the main obstacle for further improving hepatocellular carcinoma (HCC) treatment effect. Currently, single therapy for HCC in clinical practice is limited by postoperative recurrence, intraoperative blood loss and poor patient outcomes. Multidisciplinary therapy has been recognized as the key to improving the long-term survival rate for HCC. However, the clinical application of HCC synthetic therapy is restricted by single functional biomaterials. In this study, a magnetic nanocomposite hydrogel (CG-IM) with iron oxide nanoparticle-loaded mica nanosheets (Iron oxide nanoparticles@Mica, IM) is reported. This biocompatible magnetic hydrogel integrated high injectability, magnetocaloric property, mechanical robustness, wet adhesion, and hemostasis, leading to efficient HCC multidisciplinary therapies including postoperative tumor margin treatment and percutaneous locoregional ablation. After minimally invasive hepatectomy of HCC, the CG-IM hydrogel can facilely seal the bleeding hepatic margin, followed by magnetic hyperthermia ablation to effectively prevent recurrence. In addition, CG-IM hydrogel can inhibit unresectable HCC by magnetic hyperthermia through the percutaneous intervention under ultrasound guidance.

Applying Lipidomics to Non-Alcoholic Fatty Liver Disease: A Clinical Perspective.

The prevalence of Non-alcoholic fatty liver disease (NAFLD) and associated complications, such as hepatocellular carcinoma (HCC), is growing worldwide, due to the epidemics of metabolic risk factors, such as obesity and type II diabetes. Among other factors, an aberrant lipid metabolism represents a crucial step in the pathogenesis of NAFLD and the development of HCC in this population. In this review, we summarize the evidence supporting the application of translational lipidomics in NAFLD patients and NAFLD associated HCC in clinical practice.

Combination of Lenvatinib and Proton Beam Therapy in the Management of Patients With Advanced Hepatocellular Carcinoma.

This retrospective study was designed to investigate the efficacy and safety of concurrent lenvatinib and proton beam therapy (PBT) in advanced hepatocellular carcinoma (HCC) patients. Twenty HCC patients were identified, including Child-Pugh classification A in 16 patients and B (7) in four patients. Sixteen patients had macrovascular invasion, including four with main portal vein thrombosis (Vp4). The dose of lenvatinib depends on body weight; the median PBT dose was 72.6 Gy. The median progression-fee survival (PFS) and overall survival (OS) of the entire population were 8.3 months and 18.4 months, respectively. For PBT targeting intrahepatic lesions and great vessels, the objective response rate (ORR) showed a complete response and partial response (PR) of 20% and 65%, respectively. In the analysis of concurrent lenvatinib and PBT, the ORR included PR of 55% and stable disease of 25%, with disease control rate of 80%. For patients without distant metastasis upon treatment initiation, the time to local control failure (including proton in-field and out-field) was 14.3 months and distant metastasis-free survival was 17.7 months. There was no statistical difference in the analysis of PFS and OS in patients with or without portal vein thrombosis. The severity of most adverse events was grades 1-2, wherein most patients tolerated the toxicities. Our study confirmed the efficacy and safety of concurrent lenvatinib and PBT. Thus, this combination therapy may be a reasonable treatment option for selected patients with advanced HCC in clinical practice.

Reproducible safety and efficacy of atezolizumab plus bevacizumab for HCC in clinical practice: Results of the AB-real study

BackgroundIMbrave150 has established the superiority of atezolizumab plus bevacizumab over sorafenib in patients with unresectable hepatocellular carcinoma (HCC). MethodsWe generated a prospectively maintained database including patients treated with atezolizumab plus bevacizumab for unresectable HCC across Europe, Asia and USA. Clinico-pathologic characteristics were assessed for their prognostic influence on overall survival (OS) and progression-free survival (PFS) in univariable and multivariate analyses. Overall response rate by RECIST v1.1 and treatment-related adverse events (TRAEs) per CTCAE v.5.0 were reported. ResultsOut of 433 patients, 296 Child-Pugh A and ECOG performance status01 patients received atezolizumab plus bevacizumab in first line and were included. Patients were mostly male (82.7%), cirrhotic (75%) with history of viral hepatitis (65.9%). Overall, 68.9% had Barcelona Clinic Liver Cancer C-stage HCC with portal vein tumour thrombosis (PVTT, 35%) and extrahepatic spread (EHS, 51.7%). After a median follow-up of 10.0 months (95% confidence interval (CI): 9.4–10.4), median OS and PFS were 15.7 (95% CI: 14.5-NE) and 6.9 months (95% CI: 6.1–8.3), respectively. In the response-evaluable patients (n = 273), overall response rate was 30.8%. Overall, 221 patients (74.6%) developed TRAEs, with 70 (23.6%) reporting grade 3 or higher TRAEs; 25 (8.4%) patients had bleeding events. OS was independently associated with baseline Albumin-bilirubin (ALBI) grade and PVTT. Shorter PFS was associated with AFP≥ 400 ng/ml, worse ALBI and presence of EHS. ConclusionThis global observational study confirms the reproducible safety and efficacy of atezolizumab plus bevacizumab in routine clinical practice. Within Child-Pugh-A criteria, the presence of PVTT and higher ALBI grade identify patients with poorer survival.

Liver Imaging Reporting and Data System criteria for the diagnosis of hepatocellular carcinoma in clinical practice: A pictorial minireview.

Hepatocellular carcinoma (HCC) is the sixth most common cancer. The main risk factors associated with HCC development include hepatitis B virus, hepatitis C virus, alcohol consumption, aflatoxin B1, and nonalcoholic fatty liver disease. However, hepatocarcinogenesis is a complex multistep process. Various factors lead to hepatocyte malignant transformation and HCC development. Diagnosis and surveillance of HCC can be made with the use of liver ultrasound (US) every 6 mo. However, the sensitivity of this imaging method to detect HCC in a cirrhotic liver is limited, due to the abnormal liver parenchyma. Computed tomography (CT) and magnetic resonance imaging (MRI) are considered to be most useful tools for at-risk patients or patients with inadequate US. Liver biopsy is still used for diagnosis and prognosis of HCC in specific nodules that cannot be definitely characterized as HCC by imaging. Recently the American College of Radiology designed the Liver Imaging Reporting and Data System (LI-RADS), which is a comprehensive system for standardized interpretation of CT and MRI liver examinations that was first proposed in 2011. In 2018, it was integrated into the American Association for the Study of Liver Diseases guidance statement for HCC. LI-RADS is designed to ensure high sensitivity, precise categorization, and high positive predictive value for the diagnosis of HCC and is applied to “high-risk populations” according to specific criteria. Most importantly LI-RADS criteria achieved international collaboration and consensus among liver experts around the world on the best practices for caring for patients with or at risk for HCC.

Transarterial chemoembolization for hepatocellular carcinoma in clinical practice: temporal trends and survival outcomes over the last three decades in Italy

Transarterial chemoembolization for hepatocellular carcinoma in clinical practice: temporal trends and survival outcomes over the last three decades in Italy

A multivariate parametric empirical Bayes screening approach for early detection of hepatocellular carcinoma using multiple longitudinal biomarkers.

The early detection of hepatocellular carcinoma (HCC) is critical to improving outcomes since advanced HCC has limited treatment options. Current guidelines recommend HCC ultrasound surveillance every 6 months in high-risk patients however the sensitivity for detecting early stage HCC in clinical practice is poor. Blood-based biomarkers are a promising direction since they are more easily standardized and less resource intensive. Combining of multiple biomarkers is more likely to achieve the sensitivity required for a clinically useful screening algorithm and the longitudinal trajectory of biomarkers contains valuable information that should be utilized. We propose a multivariate parametric empirical Bayes (mPEB) screening approach that defines personalized thresholds for each patient at each screening visit to identify significant deviations that trigger additional testing with more sensitive imaging. The Hepatitis C Antiviral Long-term Treatment against Cirrhosis (HALT-C) trial provides a valuable source of data to study HCC screening algorithms. We study the performance of the mPEB algorithm applied to serum -fetoprotein, a widely used HCC surveillance biomarker, and des- carboxy prothrombin, an HCC risk biomarker that is FDA approved but not used in practice in the United States. Using cross-validation, we found that the mPEB algorithm demonstrated moderate but improved sensitivity compared to alternative screening approaches. Future research will validate the clinical utility of the approach in larger cohort studies with additional biomarkers.

Transarterial Chemoembolization for Hepatocellular Carcinoma in Clinical Practice: Temporal Trends and Survival Outcomes of an Iterative Treatment.

BackgroundTransarterial chemoembolization (TACE) is one of the most frequently applied treatments for hepatocellular carcinoma (HCC) worldwide. In this study, we aimed at evaluating whether and how TACE application and repetition, as well as the related outcome, have changed over the last three decades in Italy.MethodsData of 7,184 patients with HCC were retrieved from the Italian Liver Cancer (ITA.LI.CA) database. Patients were divided according to the period of diagnosis in six cohorts: P1 (1988–1993), P2 (1994–1998), P3 (1999–2004), P4 (2005–2009), P5 (2010–2014), and P6 (2015–2019). All the analyses were repeated in the overall patient population and in Barcelona Clinic Liver Cancer (BCLC) B patients, who are the subgroup of HCC patients originally supposed to receive TACE according to guidelines. TACE was defined as either the first or the main (more effective) treatment.ResultsThe proportion of patients receiving TACE as first or main therapy declined over time, and less than 50% of BCLC B patients were treated with chemoembolization from P3 onward. Conversely, TACE was widely used even outside the intermediate stage. Survival of TACE-treated patients progressively increased from P1 to P6. Although TACE was performed only once in the majority of patients, there was an increasing proportion of those receiving 2 or ≥3 treatments sessions over time. The overall survival (OS) of patients undergoing repeated treatments was significantly higher compared to those managed with a single TACE (median OS 40.0 vs. 65.0 vs. 71.8 months in 1, 2, and ≥3 TACE groups, respectively; p < 0.0001). However, after a first-line TACE, the adoption of curative therapies provided longer survival than repeating TACE (83.0 vs. 42.0 months; p < 0.0001), which in turn was associated with better outcomes compared to systemic therapies or best supportive care (BSC).ConclusionsDespite a decline in the percentage of treated patients over time, TACE has still an important role in the management of HCC patients. The survival of TACE-treated patients gradually improved over time, probably due to a better patient selection. Iterative TACE is effective, but an upward shift to curative therapies provides better outcomes while transition to systemic therapies and BSC leads to a worse prognosis.

Identification of molecular subtypes and prognostic signature for hepatocellular carcinoma based on genes associated with homologous recombination deficiency

Hepatocellular carcinoma (HCC) is a rapidly developing digestive tract carcinoma. The prognosis of patients and side effects caused by clinical treatment should be better improved. Nonnegative matrix factorization (NMF) clustering was performed using 109 homologous recombination deficiency (HRD)-related of HCC genes from The Cancer Genome Atlas (TCGA) database. Limma was applied to analyze subtype differences. Immune scores and clinical characteristics of different subtypes were compared. An HRD signature were built with least absolute shrinkage operator (LASSO) and multivariate Cox analysis. Performance of the signature system was then assessed by Kaplan–Meier curves and receiver operating characteristic (ROC) curves. We identified two molecular subtypes (C1 and C2), with C2 showing a significantly better prognosis than C1. C1 contained 3623 differentially expressed genes. A 4-gene prognostic signature for HCC was established, and showed a high predicting accuracy in validation sets, entire TCGA data set, HCCDB18 and GSE14520 queues. Moreover, the risk score was validated as an independent prognostic marker for HCC. Our research identified two molecular subtypes of HCC, and proposed a novel scoring system for evaluating the prognosis of HCC in clinical practice.

Real-Life Clinical Data of Lenvatinib versus Sorafenib for Unresectable Hepatocellular Carcinoma in Italy.

BackgroundLenvatinib has been approved in Italy since October 2019 as a first-line therapy for advanced hepatocellular carcinoma (HCC) and to date data on effectiveness and safety of lenvatinib are not available in our region. To fill this gap, we performed a multicentric analysis of the real-world treatment outcomes with the propensity score matching in a cohort of Italian patients with unresectable HCC who were treated with either sorafenib or lenvatinib.Aims and MethodsTo evaluate the effectiveness of sorafenib and lenvatinib as primary treatment of advanced HCC in clinical practice we performed a multicentric analysis of the treatment outcomes of 288 such patients recruited in 11 centers in Italy. A propensity score was used to mitigate confounding due to referral biases in the assessment of mortality and progression-free survival.ResultsOver a follow-up period of 11 months the Cox regression model showed 48% reduction of death risk for patients treated with lenvatinib (95% CI: 0.34–0.81; p = 0.0034), compared with those treated with sorafenib. The median PFS was 9.0 and 4.9 months for lenvatinib and sorafenib arm, respectively. Patients treated with lenvatinib showed a higher percentage of response rate (29.4% vs 2.8%; p < 0.00001) compared with patients treated with sorafenib. Sorafenib was shown to be correlated with more HFSR, diarrhea and fatigue, while lenvatinib with more hypertension and fatigue.ConclusionOur study highlighted for the first time the efficacy and safety of lenvatinib in an Italian cohort of patients.

The Prognostic Values of Neutrophil-to-lymphocyte Ratio and Platelet-to-Lymphocyte Ratio at Baseline in Predicting the In-hospital Mortality in Black African Patients with Advanced Hepatocellular Carcinoma in Palliative Treatment: A Comparative Cohort Study.

BackgroundThe prognostic values of the neutrophil-to-lymphocyte ratio (NLR) and the platelet-to-lymphocyte ratio (PLR) in predicting the in-hospital mortality of Black African patients with advanced hepatocellular carcinoma (HCC) in palliative treatment is unknown.AimTo determine the prognostic value of NLR and PLR compared with that of Child–Turcotte–Pugh (CTP), model for end-stage liver disease (MELD) scores and the Barcelona clinic liver cancer staging system (BCLC).MethodsThe cutoffs, accuracies and association with the mortality of these prognostic scores were determined using a time-dependent area under receiver operating characteristic curves (AUC), the log rank test and Cox proportional hazards ratio.ResultsA total of 104 patients with advanced HCC (median age=49.5 years, males=58.7%) were enrolled. All were hospitalized for an enlarged liver mass of at least 15.4 cm in size in the right thoracic quadrant. Overall, 46 (44.2%) patients died in hospital during follow-up. Patients with NLR >2.5 (log rank test=7.11, p=0.01) or PLR >92 (log rank test=5.63, p=0.02) had poor survival. Factors associated with the in-hospital mortality were the MELD score (p=0.01), NLR (p=0.03) and hemoglobin level (p=0.02). NLR exhibits better and stable accuracy in predicting the in hospital mortality at time points of 30 (AUC=0.618), 60 (AUC=0.680) and 90 (AUC=0.613) days of follow-up, compared with CTP, MELD scores, BCLC and PLR. However, PLR displayed an enhanced accuracy over 90 days of follow up (AUC=0.688).ConclusionNLR is useful in predicting the in-hospital mortality in Black African patients with advanced stage HCC in clinical practice. NLR and PLR may be used concomitantly for long-term follow-up.

Advances in clinical research on vascular interventional therapy for hepatocellular carcinoma

Vascular interventional therapy for hepatocellular carcinoma (HCC) is the most important treatment modality for unresectable HCC, including transcatheter arterial chemoembolization and hepatic arterial infusion chemotherapy. With the development and application of new materials and surgical procedures, the above treatment regimens have been modified and optimized, and various clinical studies have discussed the clinical effect of different regimens in the treatment of HCC and have made new achievements, which provides new strategies and a theoretical basis for vascular interventional therapy for HCC in clinical practice. This article summarizes the new advances in the clinical research on vascular interventional therapy for HCC.

Initial Experience of Atezolizumab Plus Bevacizumab for Advanced Hepatocellular Carcinoma in Clinical Practice.

The aim of this study was to investigate the outcomes of atezolizumab plus bevacizumab in patients with advanced hepatocellular carcinoma (HCC), including those with disease refractory to lenvatinib, in clinical practice. Of 34 patients treated with atezolizumab plus bevacizumab, a total of 23, including 16 with lenvatinib failure, were enrolled in this retrospective study. The adverse events, changes in liver function and antitumor responses at 6 weeks after starting therapy were evaluated. The incidence of grade 3 adverse events was low, at 13.0%. Albumin-bilirubin scores did not worsen at 3 and 6 weeks compared to baseline. The objective response rate and disease control rate at 6 weeks were 17.4% and 78.3% according to Response Evaluation Criteria in Solid Tumors (RECIST), and 30.4% and 78.3% according to modified RECIST, respectively. Our results suggest that atezolizumab plus bevacizumab might have potential therapeutic safety and efficacy in patients with advanced HCC, including those with disease refractory to lenvatinib. Further studies are needed to confirm the outcomes of atezolizumab plus bevacizumab after lenvatinib failure.

Targeting WEE1 by adavosertib inhibits the malignant phenotypes of hepatocellular carcinoma

Targeting the cell cycle checkpoints and DNA damage response are promising therapeutic strategies for cancer. Adavosertib is a potent inhibitor of WEE1 kinase, which plays a critical role in regulating cell cycle checkpoints. However, the effect of adavosertib on hepatocellular carcinoma (HCC) treatment, including sorafenib-resistant HCC, has not been thoroughly studied. In this study, we comprehensively investigated the efficacy and pharmacology of adavosertib in HCC therapy. Adavosertib effectively inhibited the proliferation of HCC cells in vitro and suppressed tumor growth in HCC xenografts and patient-derived xenograft (PDX) models in vivo. Additionally, adavosertib treatment effectively inhibited the motility of HCC cells by impairing pseudopodia formation. Further, we revealed that adavosertib induced DNA damage and premature mitosis entrance by disturbing the cell cycle. Thus, HCC cells accumulating DNA damage underwent mitosis without G2/M checkpoint arrest, thereby leading to mitotic catastrophe and apoptosis under adavosertib administration. Given that sorafenib resistance is common in HCC in clinical practice, we also explored the efficacy of adavosertib in sorafenib-resistant HCC. Notably, adavosertib still showed a desirable inhibitory effect on the growth of sorafenib-resistant HCC cells. Adavosertib markedly induced G2/M checkpoint arrest and cell apoptosis in a dose-dependent manner, confirming the similar efficacy of adavosertib in sorafenib-resistant HCC. Collectively, our results highlight the treatment efficacy of adavosertib in HCC regardless of sorafenib resistance, providing insights into exploring novel strategies for HCC therapy.

The dose-optimisation of lenvatinb for patients with unresectable hepatocellular carcinoma in clinical practice: A retrospective analysis of real-world evidence in China.

280 Background: Lenvatinib has become available as first-line therapy in patients with unresectable hepatocellular carcinoma (u-HCC). Although 8mg or 12mg/day is the standard starting dose according to weight, the high rate of adverse events (AEs) leading to dose reduction often limits its application. Various dosing schedules are used clinically to alleviate toxicities in practice. This study evaluated the safety and antitumor activity of two dosing strategies for lenvatinib administrations. Methods: Patients administered lenvatinib for u-HCC between April 2018 and July 2019 were enrolled. The dose-escalation strategy was conducted as follow, starting dose 4mg/day orally with biweekly escalation (As common AE always occurred within 2 weeks after administered), per 4 mg increment, to 8 or 12mg finally per body weight if no significant drug-related (no more than G2) adverse events occurred. Patients with a standard-dose strategy (8/12mg/day orally per body weight) were also included for comparison.Objective response rate(ORR) and progression-free survival (PFS) were assessed according to RECIST1.1 criteria. Dose-reduction rate was recorded and treatment-related adverse events (TRAE) was evaluated according to the CTCAE 5.0. Results: Totally 56 patients were included (37 in dose-escalation group and 19 in standard-dose group). The mean weight was 64.79±1.66 kg in dose-escalation group and 58.76±2.45 kg in standard-dose group, BCLC stage C proportion was 51.4% and 63.2%, Child-pugh B proportion was 16.2% and 5.3% respectively. Baseline demographic parameters were comparable between two groups (P&gt;0.05). There was no significant difference in response rate (32.43% vs 42.1%, P=0.335), disease control rate (86.4% vs 84.2%, P=0.686) and PFS (P=0.631). The proportion of patients who reached the full dose (per weight) was also similar (48.6% vs 63.2%, p=0.399). Dose reduction rate was significantly higher in standard-dose group than dose-escalation group (36.8%vs 13.5%,p=0.044). Although, no difference in grade 3/4 adverse events was found between two groups (P=0.083), patients in standard-dose group(36.8%,7/19) have a higher incidence trend of G3/4 AEs than those of dose-escalation group(16.2%,6/37). Conclusions: The dose-escalation strategy may be an alternative approach to prolong lenvatinib treatment period, with comparable efficacy and more tolerance. More data are needed to confirm the long-term efficacy and safety of the dose-escalation strategy.

Imaging diagnosis of hepatocellular carcinoma: LI-RADS.

Liver cancer is the third most common cause of cancer related death worldwide, 90% being hepatocellular carcinoma (HCC) and about half of all HCCs estimated to occur in China. Imaging plays a pivotal role in the management of HCC. When stringent criteria are applied to at-risk populations, it enables HCCs to be diagnosed by imaging alone without further need of invasive histology confirmation. To optimize HCC imaging diagnosis and reporting, several systems have been proposed. The Liver Imaging Reporting and Data System (LI-RADS®) is currently the most comprehensive of these systems, providing guidance on all imaging-related aspects of HCC, from technique for acquisition, reporting, assessment of treatment response and management. For diagnosis, LI-RADS uses major and ancillary imaging features to assign hierarchical categories that communicate the relative probability of HCC to focal liver observations detected in patients at risk. Two LI-RADS algorithms yield high specificity and positive predictive value for HCC diagnosis on contrast enhanced ultrasound (CEUS), CT and MRI. The standardized lexicon and interpretation provided by LI-RADS also improve inter-reader agreement for imaging features and lesion categorization. Additionally, a LI-RADS treatment response algorithm (LR-TR) provide imaging criteria for assessment of response to locoregional therapy. LI-RADS is designed for universal adoption and in this review, we highlighted the most relevant aspects of LI-RADS for the diagnosis of HCC in clinical practice and discussed areas where LI-RADS and Asian guidelines are different.

Safety and Efficacy of Lenvatinib Treatment in Child-Pugh A and B Patients with Unresectable Hepatocellular Carcinoma in Clinical Practice: A Multicenter Analysis.

PurposeTo assess the safety, efficacy and prognostic impact of clinical factors related to lenvatinib treatment in Child-Pugh class A (CP-A) and class B (CP-B) patients with unresectable hepatocellular carcinoma (u-HCC).MethodsPatients with u-HCC who were treated with lenvatinib at multiple centers in Japan were retrospectively analyzed for treatment outcomes according to their respective CP status. Radiological objective response (OR) was assessed using modified response evaluation criteria in solid tumors (mRECIST) guidelines.ResultsBaseline demographic parameters were comparable between 126 (69.6%) patients with CP-A disease and 55 patients (30.4%) with CP-B disease. Frequency of lenvatinib-related adverse events, including decreased appetite (P=0.034), diarrhea (P=0.040), elevated serum bilirubin (P=0.016) and vomiting (P=0.009), were higher in CP-B than in CP-A patients. Relative dose intensity (RDI) was significantly higher in CP-A (0.69) than CP-B patients (0.50, P <0.001). Furthermore, OR rate (44.0%) was markedly higher in CP-A5 patients as compared to CP-A6 (25.5%), CP-B7 (22.2%), and CP-B8 patients (5.3%), respectively (P=0.002). In multivariable analysis, performance status (0 vs 1, 2, P=0.026), CP class (A vs B, P=0.045) and RDI (≥0.7 vs <0.7, P=0.034) were identified as factors associated with response to lenvatinib treatment. Overall survival (OS) at 12 months was significantly different between CP-A (66.3%) and CP-B patients (30.0%, P=0.002), and between CP 5–7 (59.2%) and CP 8 patients (34.8%, P=0.003). In multivariable analysis, CP class (A vs B, P=0.007) and Barcelona clinic liver cancer (BCLC) stage (B vs C, P=0.002) were associated with OS following lenvatinib treatment.ConclusionLenvatinib treatment offers significant benefits in patients with good liver function in real-world practice. The various characteristics identified in this study might be helpful as clinical predictors of response to lenvatinib and survival in clinical practice. Further studies are required to address eligibility for lenvatinib treatment in CP 7 patients.

Asiaticoside Antagonizes Proliferation and Chemotherapeutic Drug Resistance in Hepatocellular Carcinoma (HCC) Cells.

BackgroundHepatocellular carcinoma (HCC) is the fifth most prevalent malignant tumor in China after lung cancer, gastric cancer, esophageal cancer, and breast cancer, and has a high mortality rate. Though there are a series of therapeutic strategies is now available for HCC in clinical practice, the 5-year survival rate after surgery is still low. In addition, multi-drug resistance (MDR) is one of the most important factors responsible for the low survival rate and poor therapy response in HCC. Hence, novel treatment strategies and molecules for HCC need to be developed.Material/MethodsWe assessed the effect of asiaticoside, a natural product derived from Centella asiatica (L.) Urban, on HCC cell proliferation and drug resistance.ResultsOur data indicated that asiaticoside significantly inhibited the proliferation of HCC cell lines QGY-7703 and Bel-7402 in a dose- and time-dependent manner. Moreover, asiaticoside significantly induced apoptosis in QGY-7703 and Bel-7402 cells. Treatment with asiaticoside also caused G1 cell cycle arrest in QGY-7703 and Bel-7402 cells. Western blot assay results indicated that the mechanism underlying the effects of asiaticoside involves inhibiting the activity of the PI3K/Akt and MAPK/ERK pathways. Furthermore, asiaticoside significantly antagonized P-gp-mediated MDR in HCC cells.ConclusionsOur results suggest that asiaticoside has the potential to be applied in the treatment of HCC patients, but further evidence is needed to confirm our results, particularly in vivo efficacy.

Biomarkers for Hepatocellular Carcinoma-An Updated Review.

Hepatocellular carcinoma (HCC) stands third among cancer-related deaths globally. Owing to its high incidence and linked mortality, early diagnosis is alarming for patient survival and the management of patients with developing HCC requires immediate attention. Advances in the knowledge of cancer biology and recognizing unique molecular candidates, including genomic and proteomic profiles, substantiate our understanding about several biological signatures connected with HCC. Precise identification and differential diagnosis of early HCC can remarkably improve patient survival. Currently, detection of HCC in clinical practice is performed by diagnostic imaging and noninvasive methods such as evaluation of serum biomarkers, growth factors, and the like. In this review, we discuss recent developments in targeting biomarkers for HCC.