Liver Cancer In Adults Research Articles

Liver cancer in 2021: Global burden of disease study

The epidemiology of adult primary liver cancer continues to evolve, related to the increasing prevalence of metabolic disease, rising alcohol consumption, advancements in vaccination for hepatitis B (HBV), and antiviral therapy for hepatitis C (HCV). Disparities in care and the burden of liver cancer between populations persist. We assess trends in the burden of liver cancer and contributions by various etiologies across 204 countries and territories from 2010 to 2021. Utilizing the methodological framework of the Global Burden of Disease Study 2021, we analyzed global and regional temporal trends in incidence and mortality, and the contributions of various etiologies of liver disease. In 2021, there were an estimated 529202 incident cases and 483875 deaths related to liver cancer. From 2010 to 2021, global liver cancer incident cases and deaths increased by 26% and 25%, respectively. Global age-standardized incidence rates (ASIRs) and death rates (ASDRs) for liver cancer declined but rose in the Americas and Southeast Asia. HBV remained the dominant cause of global incident liver cancer cases and deaths. Metabolic dysfunction-associated steatotic liver disease (MASLD) was the only etiology of liver cancer with rising ASIRs and ASDRs. By contrast, ASIRs and ASDRs remained stable for alcohol-related liver cancer, and declined for HBV- and HCV-related liver cancer. While age-adjusted incidence and deaths from liver cancer have started to decline, the absolute number of incident cases and deaths continues to increase. Population growth and aging contribute to the observed disconnect in the temporal trends of absolute cases and rates. Disparities remain, and MASLD-related liver cancer continues to surge.

The global burden of primary liver cancer and underlying etiologies from 1990 to 2021.

10573 Background: Liver cancer is a leading cause of global health burden, and was the seventh leading cause of cancer death in 2021. The most common type of liver cancer in adults is hepatocellular carcinoma, which can be due to alcohol, hepatitis B, hepatitis C, non-alcoholic steatohepatitis (NASH), or other causes. In children the most common type of liver cancer is hepatoblastoma. Comprehensive and comparative estimation of liver cancer burden can inform policy decisions and public health interventions to reduce incidence, morbidity, and mortality. This study provides updated liver cancer estimates from 1990 to 2021, and for the first time includes hepatoblastoma. Methods: Using estimation methods from the Global Burden of Diseases, Injuries, and Risk Factors Study 2021 (GBD 2021) we comprehensively estimated total liver cancer incidence, mortality, prevalence, years lived with disability (YLDs), years of life lost (YLLs), and disability adjusted life-years (DALYs). Etiologic proportions from meta-analyses of literature review data were applied to the total. Liver cancers under age 10 were attributed to hepatoblastoma. YLLs were calculated using life expectancy estimates. Prevalence and YLDs were calculated from expected survival, disease sequelae, and disability weights. DALYs were the sum of YLLs and YLDs. Results are presented with 95% Uncertainty Intervals (95% UI). Results: Globally, there were an estimated 529,000 (95% UI 480,000 – 594,000) liver cancer cases and 484,000 (437,000 – 538,000) deaths in 2021, contributing to 12,900,000 (11,600,000 – 14,400,000) DALYs. Since 1990, these represented increases of 114.3% (87.0 – 145.3%) in cases, 102.5% (76.4 – 132.0%) in deaths, and 70.6% (48.7 – 96.8%) in DALYs. For liver cancer etiologies (excluding hepatoblastoma), 37.4% (32.6 – 42.6%) of deaths were due to hepatitis B, 30.3% (26.3 – 34.8%) hepatitis C, 19.1% (15.8 – 22.8%) alcohol, 8.5% (6.9 – 10.3%) NASH, and 4.3% (3.6 – 5.1%) other causes in 2021. Conclusions: These GBD 2021 estimates provide comprehensive estimates of the substantial health burden of liver cancer, highlighting a continued need for public health efforts targeting prevention, vaccination, treatment, or behavioral change.[Table: see text]

Liver cancer in young adults: Validity of global data sets.

Liver cancer in young adults: Validity of global data sets.

Diabetes is associated with increased liver cancer incidence and mortality in adults: A report from Asia Cohort Consortium.

There has been growing evidence suggesting that diabetes may be associated with increased liver cancer risk. However, studies conducted in Asian countries are limited. This project considered data of 968,738 adults pooled from 20 cohort studies of Asia Cohort Consortium to examine the association between baseline diabetes and liver cancer incidence and mortality. Cox proportional hazard model and competing risk approach was used for pooled data. Two-stage meta-analysis across studies was also done. There were 839,194 subjects with valid data regarding liver cancer incidence (5654 liver cancer cases [48.29/100,000 person-years]), follow-up time and baseline diabetes (44,781 with diabetes [5.3%]). There were 747,198 subjects with valid data regarding liver cancer mortality (5020 liver cancer deaths [44.03/100,000 person-years]), follow-up time and baseline diabetes (43,243 with diabetes [5.8%]). Hazard ratio (HR) (95% confidence interval [95%CI]) of liver cancer diagnosis in those with vs. without baseline diabetes was 1.97 (1.79, 2.16) (p < .0001) after adjusting for baseline age, gender, body mass index, tobacco smoking, alcohol use, and heterogeneity across studies (n = 586,072; events = 4620). Baseline diabetes was associated with increased cumulative incidence of death due to liver cancer (adjusted HR (95%CI) = 1.97 (1.79, 2.18); p < .0001) (n = 595,193; events = 4110). A two-stage meta-analytic approach showed similar results. This paper adds important population-based evidence to current literature regarding the increased incidence and mortality of liver cancer in adults with diabetes. The analysis of data pooled from 20 studies of different Asian countries and the meta-analysis across studies with large number of subjects makes the results robust.

Incidence of liver cancer in young adults according to the Global Burden of Disease database 2019.

The worldwide burden of cancer is increasing in younger populations. However, the epidemiology of primary liver cancer remains understudied in young adults compared to other cancer forms. This study analyzed data from the Global Burden of Disease study between 2010 and 2019 to assess the age-standardized incidence, mortality, and disability-adjusted life years associated with primary liver cancer in the young (15-49y), stratified by region, nation, sociodemographic index, and sex. The study found a global estimate of 78,299 primary liver cancer cases, 60,602 deaths, and 2.90 million disability-adjusted life years in the young population. The Western Pacific region exhibited the highest burden in 2019, showing the most significant increase compared to other regions between 2010 and 2019. More than half of the countries worldwide have undergone an increase in primary liver cancer incidence rates in young adults. Around 12.51% of deaths due to primary liver cancer occur in young individuals. Throughout the study period, there was a significant decline in primary liver cancer mortality due to most etiologies, except for metabolic dysfunction-associated steatotic liver disease-attributable primary liver cancer (annual percentage change + 0.87%, 95% CI: 0.70%-1.05%) and alcohol-attributable primary liver cancer (annual percentage change + 0.21%, 95% CI: 0.01%-0.42%). The limitations of the Global Burden of Disease database include reliance on the quality of primary data and possible underestimation of alcohol consumption. Over the past decade, there has been a marked increase in the burden of primary liver cancer, especially that originating from steatotic liver disease. This trend calls for the development of urgent and comprehensive strategies to mitigate this rising burden globally.

Abstract 5729: ADCK1 inhibition alters cell proliferation and cell cycle progression in liver cancer cells

Abstract In 2020, there were over 830,000 reported liver cancer deaths. Incidence rates of liver cancer have tripled, and death rates have doubled since the 1980s; giving this disease one of the highest mortality rates when compared to its incidence rate. Hepatocellular carcinoma (HCC) is derived from hepatocytes and is the main type of liver cancer in adults, accounting for 75-85% of all primary liver cancers. Current treatment options for HCC like radiation therapy and chemotherapy are imperfect and cause significant side effects. Tumorigenesis is dependent on an organism’s cellular metabolism. Metabolic reprogramming is a promising area of focus for cancer therapeutics. Cancer cells thrive in nutrient-deficient environments by hijacking and reprogramming the cells existing cellular metabolism. Metabolic reprogramming is driven by genetic alterations and environmental cues. AarF Domain Containing Kinase 1 (ADCK1) is a protein-coding gene that acts as a mitochondrial protein with putative kinase activity. The role of ADCK1 has not been well studied, particularly in liver cancer. Our group has sought to study how ADCK1 impacts the metabolism and cellular environment of HCC cells to help establish a more effective drug target. Bioinformatics performed by our lab report that ADCK1 was highly expressed in HCC tumor cells. The expression levels of ADCK1 were also correlated with a decrease in patient survival. ADCK1 knockout clones were generated; these knockout cells showed decreased proliferation and altered cell cycle progression. Proteomics analysis demonstrated that loss of ADCK1 was also seen to alter the expression of proteins involved in several cellular processes related to the cell cycle and cellular metabolism. How ADCK1 regulates these processes will be studied in the future. Citation Format: Noel A. Jacquet, Yunfeng Zhao. ADCK1 inhibition alters cell proliferation and cell cycle progression in liver cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5729.

Abstract 822: A retrospective study on the disparities of hepatocellular carcinoma

Abstract Background: Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer in adults and the third leading cause of cancer-related deaths worldwide. Studies report that the incidence of, and mortality from HCC vary significantly by age, sex, and race/ethnicity; however, disparities in the expression level of tumor biomarkers, liver functions, lipid profiles, and comorbidities have not been thoroughly investigated among subpopulations of patient with HCC. Methods: A retrospective study was conducted to review 247 serial HCC cases enrolled in the University of Mississippi Medical Center during June 2000 to May 2023. The entire HCC population was stratified into subpopulations by race, gender, age and BMI. Then comparisons were performed between two corresponding subpopulations in the expression level of HCC-related biomarkers including Alpha-FP, liver functions including albumin, ALT, AST, and ALP, plasma lipid profiles including cholesterol, and comorbidity conditions including cirrhosis in benign liver tissues, smoking, alcohol using, and illness with viral hepatitis. Two-tailed Student’s T-test was used to calculate the difference in mean values, and Chi-Square Test was used to compare the difference in rates or percentages. The significant p value was set at p&amp;lt;0.05. Results: In total 247 HCC cases, males were 178 (72.1%) and females were 69 (27.9%) with a male to female ratio of 2.6:1; black patients were 108 (43.7%), white patients were 127 (51.4%), and others were 4.9%. The mean age was 59.6 years and mean BMI was 27.04. AFP was the only one of detected tumor biomarkers showing disparities: it was significantly higher in patients of male (p=0.026), younger age (p&amp;lt;0.0001), lower BMI (p=0.039), smokers (p=0.0325) and illness with viral hepatitis (p=0.0007). Disparities in liver functions included: 1) AST was significantly higher in Black HCC patients (p=0.027); 2) no statistical difference of liver functions in gender; 3) younger HCC patients had significantly lower level of Albumin (p=0.006), and higher levels of ALT (p=0.014) and AST (p=0.0032); 4) HCC patients with lower BMI also had lower level of Albumin (p=0.015), and higher levels of AST (p=0.0480 and ALP (p=0.0057). There was no statistical difference of plasma lipid profiles between subpopulations, Black HCC patients except that Black HCC patients had significantly higher levels of cholesterol (p=0.0006) and HDL (p=0.048). In comorbidity, Black HCC patients had higher rates of alcohol using and existence of cirrhosis; and male HCC patients had higher rates of smoking, alcohol usage and viral hepatitis. Conclusions: HCC patients are greatly disparate in the expression level of tumor biomarkers, liver functions, plasma lipid profiles and comorbidity conditions between subpopulations stratified by race, gender, age and BMI. These results could provide useful information for clinical management and prognosis of patients with HCC. Citation Format: Xinchun Zhou, Barrett Aldridge, Nazar Rahmanov, Zhirong Liu, Jinghe Mao, Neha Varshney. A retrospective study on the disparities of hepatocellular carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 822.

Modeling the Risk of Liver Cancer in Adults: A Machine Learning Investigation into the Role of Obesity and Overweight

Background: Liver cancer is a global health concern, with overweight and obese individuals exhibiting an increased risk of its development. Understanding the interplay between obesity-related factors and liver cancer incidence is crucial for early prediction and intervention. Aim: The aim of this investigation was to construct and validate an extreme gradient boosting (XGBoost) based machine learning model for the purpose of establishing a one-year liver cancer risk prediction system specifically tailored to overweight and obese patients. In addition, this study sought to compare the predictive performance of the XGBoost model with those of a random forest model and a logistic regression model, while also identifying the most influential predictive features for liver cancer incidence. Methods: A comprehensive retrospective analysis was conducted on MIMIC III data comprising 2,354 patients. To predict the risk of liver cancer development, three machine learning models were developed: XGBoost, random forest, and logistic regression. Feature selection was executed using a stepwise regression procedure encompassing both forward selection and backward elimination. Results: The stepwise regression technique unveiled 14 predictive factors for liver cancer incidence. Among the patient cohort, 132 individuals developed liver cancer within a year of follow-up, while 2,222 did not. Notably, most liver cancer cases occurred in male patients (60%). Statistically significant differences were observed between patients with liver cancer and those without, in terms of age, gender, total bilirubin, platelet, albumin, chloride, potassium, sodium, prothrombin time (PT) and alanine aminotransferase (ALT). The XGBoost model exhibited an impressive area under the receiver operating characteristic curve (AUROC) of 99%, Random Forest (RF) of 99%, and Logistic Regression (LR) of 90%. In a multivariate analysis, total bilirubin, creatinine levels, age, gender, ALT, alkaline phosphate (ALP), PT, calcium, and chloride emerged as independent predictors for liver cancer incidence. Conclusion: The XGBoost model demonstrated superior predictive performance when compared to the RF and LR models. If corroborated through prospective studies, the XGBoost model may prove to be a valuable tool for the early prediction of liver cancer risk in overweight or obese individuals. Such predictive capabilities could, in turn, facilitate the implementation of timely preventive interventions against liver cancer.

Hepatitis B immunization strategies and its associated factors: A narrative review.

Hepatitis B is a major public health concern as one third of the world's population is infected with hepatitis B virus (HBV). The risk of HBV infection remains primarily through percutaneous or mucosal contact with infected blood or body fluids. To update the society on hepatitis B immunization strategies and its associated factors. The review paper utilized different search engines such as Pubmed Central, Scopus, Web of Science, Google Scholar, and so onto conduct this review paper. Improving immunity through general vaccination recommendations has reduced the number of chronic hepatitis B cases among children and adolescents, but an influx of infections from endemic countries has increased the number of chronically infected adults. This is due to immigration from endemic countries to Hepatitis less burden areas like developed countries. Introduction of infant immunization programs in some countries has reportedly reduced the prevalence of HBV infection and reduced the incidence of liver cancer in children and young adults. While hepatitis B vaccination coverage is low, a significant number of people are not adhering to full hepatitis B vaccination posing a potential hazard to health.

B-364 Inhibition of Hypoxia-Inducible Factor-1a (HIF-1 a) Provides a Therapeutic Approach for Hepatocellular Carcinoma (HCC)

Abstract Background The most frequent type of primary liver cancer in adults is hepatocellular carcinoma (HCC) which is the third-highest cause of cancer-related death worldwide. Globally, people die from liver cancer each year, with HCC accounting for around 90% of those deaths, making it a serious public health concern. Cirrhosis, hepatitis B, hepatitis C, and non-alcoholic fatty liver disease are all high-risk factors for HCC development. In addition, HCC is one of the most frequent solid tumors found in humans. Due to insufficient blood supply, these solid tumors usually are devoid of oxygen and nutrients. A reduction in oxygen concentration results in the formation of a hypoxic environment that downregulates the metabolic process and is fatal to cancer cells. To circumvent this barrier to growth, cancer cells produce hypoxia-inducible factor-1 (HIF-1), which alters their metabolic pathways and allows them to survive. HIF-1alpha (HIF-1α), a cytoplasmic subunit of HIF-1 can be overexpressed in hypoxic conditions. HCC cells cannot proliferate under hypoxia without a high level of HIF-1α expression, making it as a potential cancer treatment target. Using the LOPAC (Library of Pharmacologically Active Compounds) drug library, we have identified multiple drug molecules that inhibit the expression of HIF-1α. Methods We constructed specific SK-HEP-1 cells, a human liver cancer cell line, expressing the luciferase reporter gene under the promoter of HIF-1α. By using the cells, we screened the (LOPAC) library. Other bioanalytical methods were used to confirm and analyze identified candidates. Results We successfully identified several compounds that are able to inhibit HIF-1α expression by using luciferase activity assays and Western blot analysis (WB). Further investigation was conducted to determine the molecular mechanism and function for one of the drug candidates, termed as UZ-1, in inhibiting HIF-1α in HCC by using the MTT assay and WB. UZ-1, an antirheumatic agent, showed a strong inhibitory effect on the expression of HIF-1α in SK-HEP-1 cells. In addition, it suppressed the signaling pathways associated with HIF-1α, leading to the apoptosis of HCC cells. Conclusion The UZ-1 molecule inhibits HIF-1α expression, as a result, and displays anticancer function in HCC cells through inducing apoptosis. Our result suggests that UZ-1 may be a potential drug candidate for the treatment of HCC.

Gd-EOB-DTPA-Enhanced Magnetic Resonance Imaging Combined with T1 Mapping Identifies Dysplastic Module and Hepatocellular Carcinoma: A Retrospective Study.

Hepatocellular carcinoma (HCC) is the leading type of liver cancer in adults, often resulting in fatal outcomes for those with cirrhosis. Dysplastic nodule (DN) is a liver nodule that is substantial in size, ranging from 1-2 cm. However, accurately distinguishing between DN and HCC on imaging has posed a challenge. The aim of this study is to assess the usefulness of Gd-EOB-DTPA-enhanced MRI T1 mapping in distinguishing between DN and HCC. This study analyzed 66 patients with confirmed HCC or DN who underwent Gd-EOB-DTPA-enhanced MRI T1 mapping before surgery or puncture at the Army Medical Center in China. The T1 values of each lesion were measured before and after Gd-EOB-DTPA administration, and various calculations were made, including absolute and percentage reduction in T1 value and coefficient of variation. The t-test was used to compare these values between the two groups, and the efficacy of T1 mapping values for differential diagnosis of HCC and DN was evaluated using the receiver operating characteristic curve (ROC). The study found that T1pre, T1hp, ΔT1, ΔT1%, and CV in the HCC group were significantly higher than in the DN group (p < 0.01). The accuracy of T1hp, ΔT1, and CVT1-hp in identifying HCC from DN was high, with AUCs of 0.955, 0.910, and 0.932, respectively. ΔT1% also had some accuracy, with an AUC of 0.818. Our results provide preliminary evidence that Gd-EOB-DTPA-enhanced MRI T1, CVT1-hp mapping, can be a valuable tool in diagnosing and differentiating between HCC and DN.

LipoCol Forte capsules reduce the risk of liver cancer: A propensity score-matched, nationwide, population-based cohort study.

Liver cancer is among the top five most common cancers globally. Lipid-lowering drugs such as statins can lower the risk of liver cancer, but may also cause liver damage. LipoCol Forte capsules (LFC), a red yeast rice product, have demonstrated significant antihypercholesterolemic effects and a good safety profile in clinical studies. To evaluate whether LFC lowers the risk of liver cancer in adults in this propensity score-matched, nationwide, population-based cohort study. We used data from Taiwan's National Health Insurance Research Database, which includes electronic medical records for up to 99.99% of Taiwan's population. LFC users and LFC non-users were matched 1:1 by propensity scores between January 2010 and December 2017. All had follow-up data for at least 1 year. Statistical analyses compared demographic distributions including sex, age, comorbidities, and prescribed medications. Cox regression analyses estimated adjusted hazard ratios (aHRs) after adjusting for potential confounders. We enrolled 33231 LFC users and 33231 non-LFC users (controls). No significant differences between the study cohorts were identified regarding comorbidities and medications [standardized mean difference (SMD) < 0.05]. At follow-up, the overall incidence of liver cancer was significantly lower in the LFC cohort compared with controls [aHR 0.91; 95% confidence interval (CI): 0.86-0.95; P < 0.001]. The risk of liver cancer was significantly reduced in both females (aHR 0.87; 95%CI: 0.8-0.94; P < 0.001) and males (aHR 0.93; 95%CI: 0.87-0.98; P < 0.01) in the LFC cohort compared with their counterparts in the non-LFC cohort. The antitumor protective effects applied to patients with comorbidities (including hypertension, ischemic stroke, diabetes mellitus, hyperlipidemia, hepatitis B infection and hepatitis C infection). Those using LFC for more than 84 drug days had a 0.64-fold lower risk of liver cancer compared with controls (P < 0.001). Compared with controls, the risk of developing liver cancer in the LFC cohort progressively decreased over time; the lowest incidence of liver cancer occurred in LFC users followed-up for more than 6 years (27.44 vs 31.49 per 1,000 person-years; aHR 0.75; 95%CI: 0.68-0.82; P < 0.001). This retrospective cohort study indicates that LFC has a significantly protective effect on lowering the risk of liver cancer, in a dose-dependent and time-dependent manner.

Dexamethasone-stimulated glucocorticoid receptor signaling positively regulates the endoplasmic reticulum-associated degradation (ERAD) mechanism in hepatocellular carcinoma cells

Hepatocellular carcinoma is one of the most common types of primary liver cancer in adults and also it is the third leading cause of cancer-related deaths worldwide. Although there are various treatment options such as surgery, radiation, targeted drug therapy, immunotherapy and chemotherapy, most hepatocellular carcinomas are highly resistant to systemic treatments. Today, the molecular pathogenesis of hepatocellular carcinoma remains largely obscure. Therefore, there is a need for detailed research for the characterization of molecular signaling networks related to the development of hepatocellular carcinoma. Recent studies have attention to the hormonal regulation of hepatocellular carcinoma cells mediated by systemic hormones such as glucocorticoids. However, glucocorticoid-mediated regulation of endoplasmic reticulum-associated degradation (ERAD) and unfolded protein response (UPR), which are known to be important survival mechanisms for cancer cells remains unknown in hepatocellular carcinoma. In the present study, we showed that dexamethasone-induced glucocorticoid receptor signaling mediated advanced regulation of ERAD and UPR signaling in hepatocellular carcinoma cells. Our findings indicated that glucocorticoid signaling positively regulated mRNA and protein levels of ERAD components and also protein kinase RNA-like ER Kinase (PERK) and inositol-requiring enzyme 1⍺ (IRE1⍺) branches of UPR signaling are accompanied by the glucocorticoid signaling. In addition, putative glucocorticoid response elements (GREs) were determined in the promoter regions of ERAD members in in-silico analyses. Additionally, silencing of ERAD components significantly reduced the tumorigenic features of hepatocellular carcinoma cells, including cell proliferation, metastasis, invasion and 3D tumor formation. Collectively, these results reveal a novel pattern of regulation of ERAD components by glucocorticoid-mediated in human hepatocellular carcinoma cells.

Metabolic primary liver cancer in adults: risk factors and pathogenic mechanisms

Primary liver cancer (PLC) is a heterogeneous group of disorders arising with the background of chronic liver disease (CLD) owing to varying etiologies. PLC carries a high lethality rate and a substantial epidemiological, clinical, and financial burden, which is projected to escalate. The two most common PLC histotypes in adults are hepatocellular carcinoma (HCC) and cholangiocarcinoma (CC); the latter is sub-classified as either intrahepatic CC or extrahepatic CC. Over recent decades, there has been a decline of viral CLD accompanied by an increase in dysmetabolic CLD, resulting in PLC becoming relatively more common in Western countries. Metabolic co-morbidities are risk factors and co-factors for HCC and (increasingly) CC. Complex immunological, cellular, pro-inflammatory, molecular, and genetic processes in the systemic dysmetabolic milieu increase PLC risk. Improved understanding of these mechanisms requires close surveillance and early diagnosis of at-risk patients while paving the way for personalized medicine, chemoprevention, and innovative management of metabolic PLC.

EPH4 Incidence and Survival of Patients with Hepatocellular Carcinoma in the United States from 2008 to 2018

Hepatocellular Carcinoma (HCC) is the most prevalent primary liver cancer in adults, and it is one of the fastest-rising causes of cancer-related deaths in the US. This study examined the incidence and survival rates for HCC in recent years.

Hydroxytyrosol [2-(3,4-dihydroxyphenyl)-ethanol], a natural phenolic compound found in the olive, alters Ca2+ signaling and viability in human HepG2 hepatoma cells.

Hepatotoma is the leading type of primary liver cancer in adults and third cause of death in the world. Hydroxytyrosol is a natural phenol existing in olive (Olea europaea L.). Hydroxytyrosol is the chief ingredient of olive oil, which was early deemed to be the most robust antioxidant in olive oil. Hydroxytyrosol is known to inhibit various types of cancer by different methods. This study was aimed to delineate the action of hydroxytyrosol on viability and [Ca2+]i in HepG2 hepatoma cells. Fura-2 was used to detect [Ca2+]i, and WST-1 assays were applied to explore cell cytotoxicity. Hydroxytyrosol elicited [Ca2+]i raises. Eliminating external Ca2+ diminished the Ca2+ signal by 30%. Hydroxytyrosol-evoked Ca2+ influx was diminished by 20% by three inhibitors of store-operated Ca2+ channels and by a protein kinase C activator and an inhibitor. In the absence of Ca2+, thapsigargin eradicated hydroxytyrosol-provoked [Ca2+]i raises. Suppression of phospholipase C (PLC) with U73122, a PLC inhibitor, did not inhibit hydroxytyrosol-elicited [Ca2+]i raises. Hydroxytyrosol reduced cell viability. This cytotoxic action was not reversed by preincubation with BAPTA/AM, a cytosolic Ca2+ binder. In sum, in HepG2 hepatoma cells, hydroxytyrosol elicited [Ca2+]i raises by provoking PLC-unrelated discharge of Ca2+ from ER and Ca2+ influx through PKC-sensitive store-operated Ca2+ entry. In addition, hydroxytyrosol elicited Ca2+-dissociated cytotoxicity.

Epigenetics of pediatric liver cancer and potential therapy

The pediatric liver cancer hepatoblastoma (HBL) has a complex etiology which is not yet determined.In contrast to adult liver cancer hepatocellular carcinoma (HCC), pediatric HBL has a low rate of genetic mutations suggesting that other mechanisms play a critical role in development of this disease

Serum Beclin 1 and autophagy-related protein-5 and the risk of hepatocellular carcinoma among cirrhotic hepatitis C patients

BackgroundThe most common primary liver cancer in adults is hepatocellular carcinoma (HCC) which is commonly presented with a poor prognosis. Therefore, it is important to explore effective biomarkers and therapeutic targets for HCC patients. Autophagy is involved in the development and prevention of cancer. Mammalian Beclin-1 is needed for an autophagic vesicle in HCC. Autophagy-related protein-5 (ATG5) is an important molecule involved in cell death during autophagy. The objective is to investigate serum ATG 5 and Beclin 1 levels in HCV-induced liver cirrhosis with and without HCC. The study was conducted on 80 individuals classified into 3 groups:Group 1: 30 patients with HCV-induced liver cirrhosis without HCC.Group 2: 30 patients with HCV-induced liver cirrhosis with HCC.Group 3: 20 healthy subjects (control group).ResultsSerum ATG 5 was significantly lower in HCC than liver cirrhosis patients. Serum Beclin 1 was significantly higher in HCC than liver cirrhosis patients. A cutoff value of < 95.7 and > 5.3 of serum ATG5 and Beclin 1 could be suggested for diagnosis of HCC among patients with HCV-related cirrhosis.ConclusionSerum Beclin 1 and ATG 5 could be used as a novel diagnostic marker for HCC. Moreover, scoring of serum BECLIN 1, ATG 5, and cachexia might be a future promising tool to predict the risk of HCC development.

Evaluation of the Consequence of CTNNB1 &amp; RAB1A Targeting on Hepatocellular Carcinoma Cell Line

Abstract Background Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer in adults and the most common cause of death in people with chronic liver diseases. In Egypt, liver cancer forms 11.75% of the malignancies of all digestive organs and 1.68% of the total malignancies. HCC constitutes 70.48% of all liver tumors among Egyptians. In the past few years, early diagnosis and advances in therapeutic measures have greatly improved the outcome of HCC patients. However, the prognosis is still poor with overall survival rates of 3-5%. The alterations in cancer driver genes and associated pathways are the major triggers for HCC. So, the identification and targeting of these genes are beneficial to understand HCC and to develop a new therapy. Aim of the work We aimed to target CTNNB1 and RAB1A oncogenes in HepG2 cell lines by RNAi then evaluate the effect of their targeting on the viability and proliferative activity of HepG2 cells. Materials and methods Using HepG2 cell lines, CTNNB1 &amp; RAB1A oncogenes were targeted using two different siRNAs (small interfering RNA) for each gene. The viability of HepG2 was conducted by Trypan blue test. The cell proliferation was tested by CellTiter 96® AQueous One Solution Cell Proliferation Assay. Results There was significant reduction in the cells’ viability detected by trypan blue test in transfected cells with siRNA targeting either CTNNB1 or RAB1A compared to Mock HepG2 cell lines (p &amp;lt;0.05). In addition, the proliferative activity was significantly lower in both HepG2 cell lines transfected with siRNA targeting the previous genes compared to mock cells (p &amp;lt; 0.05). Furthermore, HepG2 cells transfected with siRNA targeting RAB1A were more proliferative compared to those transfected with siRNA targeting CTNNB1 (p &amp;lt;0.05). Conclusion Targeting CTNNB1or RAB1A in HepG2 cell lines decreased the cell viability and proliferative activity. Moreover, targeting CTNNB1 was effective in decreasing cell proliferative activity compared to targeting RAB1A in HepG2 cell lines. So, targeting CTNNB1 may have a potential therapeutic effect in treatment of HCC.

The Role of the Hedgehog Pathway in Cholangiocarcinoma

Simple SummaryCholangiocarcinoma (CCA) is one of the most refractory malignancies with a high mortality rate. Among all the pathways involved in CCA development, emerging evidence highlights Hedgehog (HH) signaling as a substantial player in CCA-genesis and development. The pro-tumoral function of HH provides potential therapeutic implications, and recently the use of HH inhibitors has paved the way for clinical application in various solid tumors. Targeting HH members, namely Hedgehog ligands, SMO transmembrane protein and GLI transcription factors may thus confer therapeutic options for the improvement of CCA treatment outcome.Cholangiocarcinoma (CCA) is a poorly treatable type of cancer and, along with hepatocellular carcinoma (HCC), is the predominant type of primitive liver cancer in adults. The lack of understanding of CCA biology has slowed down the identification of novel targets and the development of effective treatments. While tumors share some general characteristics, detailed knowledge of specific features is essential for the development of effectively tailored therapeutic approaches. The Hedgehog (HH) signaling cascade regulates stemness biology, embryonal development, tissue homeostasis, and cell proliferation and differentiation. Its aberrant activation has been associated with a variety of solid and hematological human malignancies. Several HH-inhibiting compounds have been indeed developed as potential anticancer agents in different types of tumors, with Smoothened and GLI inhibitors showing the most promising results. Beside its well-established function in other tumors, findings regarding the HH signaling in CCA are still controversial. Here we will give an overview of the most important clinical and molecular features of cholangiocarcinoma, and we will discuss the available evidence of the crosstalk between the HH signaling pathway and the cholangiocarcinoma cell biology.