Management Of Hepatocellular Carcinoma Research Articles

Management of Hepatocellular Carcinoma in 2024: The Multidisciplinary Paradigm in an Evolving Treatment Landscape.

Liver cancer is the third most common cause of cancer-related deaths worldwide, and hepatocellular carcinoma (HCC) makes up the majority of liver cancer cases. Despite the stabilization of incidence rates in recent years due to effective viral hepatitis treatments, as well as improved outcomes from early detection and treatment advances, the burden of HCC is anticipated to rise again due to increasing rates of metabolic dysfunction-associated steatotic liver disease and alcohol-related liver disease. The treatment landscape is evolving and requires a multidisciplinary approach, often involving multi-modal treatments that include surgical resection, transplantation, local regional therapies, and systemic treatments. The optimal approach to the care of the HCC patient requires a multidisciplinary team involving hepatology, medical oncology, diagnostic and interventional radiology, radiation oncology, and surgery. In order to determine which approach is best, an individualized treatment plan should consider the patient's liver function, functional status, comorbidities, cancer stage, and preferences. In this review, we provide an overview of the current treatment options and key trials that have revolutionized the management of HCC. We also discuss evolving treatment paradigms for the future.

Natural products targeting macroautophagy signaling in hepatocellular carcinoma therapy: Recent evidence and perspectives.

Hepatocellular carcinoma (HCC), presently the second leading cause of global cancer-related mortality, continues to pose significant challenges in the realm of medical oncology, impacting both clinical drug selection and mechanistic research. Recent investigations have unveiled autophagy-related signaling as a promising avenue for HCC treatment. A growing body of research has highlighted the pivotal role of autophagy-modulating natural products in inhibiting HCC progression. In this context, we provide a concise overview of the fundamental autophagy mechanism and delineate the involvement of autophagic signaling pathways in HCC development. Additionally, we review pertinent studies demonstrating how natural products regulate autophagy to mitigate HCC. Our findings indicate that natural products exhibit cytotoxic effects through the induction of excessive autophagy, simultaneously impeding HCC cell proliferation by autophagy inhibition, thereby depriving HCC cells of essential energy. These effects have been associated with various signaling pathways, including PI3K/AKT, MAPK, AMPK, Wnt/β-catenin, Beclin-1, and ferroautophagy. These results underscore the considerable therapeutic potential of natural products in HCC treatment. However, it is important to note that the present study did not establish definitive thresholds for autophagy induction or inhibition by natural products. Further research in this domain is imperative to gain comprehensive insights into the dual role of autophagy, equipping us with a better understanding of this double-edged sword in HCC management.

HnRNPR-mediated UPF3B mRNA splicing drives hepatocellular carcinoma metastasis

IntroductionAbnormal alternative splicing (AS) contributes to aggressive intrahepatic invasion and metastatic spread, leading to the high lethality of hepatocellular carcinoma (HCC). ObjectivesThis study aims to investigate the functional implications of UPF3B-S (a truncated oncogenic splice variant) in HCC metastasis. MethodsBasescope assay was performed to analyze the expression of UPF3B-S mRNA in tissues and cells. RNA immunoprecipitation, and in vitro and in vivo models were used to explore the role of UPF3B-S and the underlying mechanisms. ResultsWe show that splicing factor HnRNPR binds to the pre-mRNA of UPF3B via its RRM2 domain to generate an exon 8 exclusion truncated splice variant UPF3B-S. High expression of UPF3B-S is correlated with tumor metastasis and unfavorable overall survival in patients with HCC. The knockdown of UPF3B-S markedly suppresses the invasive and migratory capacities of HCC cells in vitro and in vivo. Mechanistically, UPF3B-S protein targets the 3′-UTR of CDH1 mRNA to enhance the degradation of CDH1 mRNA, which results in the downregulation of E-cadherin and the activation of epithelial–mesenchymal transition. Overexpression of UPF3B-S enhances the dephosphorylation of LATS1 and the nuclear accumulation of YAP1 to trigger the Hippo signaling pathway. ConclusionOur findings suggest that HnRNPR-induced UPF3B-S promotes HCC invasion and metastasis by exhausting CDH1 mRNA and activating YAP1-Hippo signaling. UPF3B-S could potentially serve as a promising biomarker for the clinical management of invasive HCC.

Upregulation of RACGAP1 is correlated with poor prognosis and immune infiltration in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a primary liver cancer with high mortality worldwide. Even though the patients with HCC received standard therapies, patients with HCC continue to experience unsatisfactory therapy outcomes. Presently, immune therapy acts as a novel therapeutic management for HCC. The aim of this study was to determine overexpressed genes in HCC and evaluate the association between overexpressed genes with the prognosis and immune infiltration. Gene expression profiles of HCC were analyzed using multiple online databases, and then confirmed by qualitative real time-polymerase chain reaction (RT-qPCR) and immunohistochemical analysis. The correlations of gene overexpression with the prognosis and immune infiltration were determined. Top 11 common differentially expressed genes were identified in HCC, and RACGAP1 was selected for further analysis. RACGAP1 expression was significantly higher in HCC tissues than that in normal tissues. Upregulation of RACGAP1 was correlated with clinical stage and poor prognosis. Additionally, RACGAP1 overexpression was positively related to the infiltration of suppressive immune cells. Moreover, we speculate RACGAP1 may promote tumorigenesis of HCC through immunosuppression mediated by YAP activation. Overexpression of RACGAP1 was associated with unfavorable prognosis and immune infiltration in HCC, which indicated that RACGAP1 could be a molecular target for HCC.

Hepatocellular Carcinoma: Advances in Systemic Therapy.

Hepatocellular carcinoma (HCC) is a prevalent primary liver cancer, representing over 90% of cases globally and ranking as the third leading cause of cancer-related death. This article reviews the evolving landscape of systemic therapies for advanced HCC, emphasizing recent advancements and their impact on patient outcomes. The advent of molecular targeted therapies has transformed HCC management, with sorafenib being the first FDA-approved molecular targeted therapy, setting a standard for a decade. However, recent breakthroughs involve the combination of atezolizumab and bevacizumab, demonstrating superior outcomes over sorafenib, leading to FDA approval in 2020. Another notable combination is tremelimumab and durvalumab, showing efficacy in a multinational phase III trial. Beyond these combinations, this article explores the role of other first-line treatments and subsequent therapies after progression. The evolving landscape of systemic therapies for HCC reflects a paradigm shift, with immunotherapy combinations emerging as key players alongside targeted therapies. This article highlights the complexity of treatment decisions, considering individual patient characteristics and disease etiology, and underscores the ongoing quest to optimize both systemic and local-regional therapies for improved long-term outcomes in HCC patients.

Current status of magnetic resonance imaging radiomics in hepatocellular carcinoma: A quantitative review with Radiomics Quality Score.

Radiomics is a promising tool that may increase the value of magnetic resonance imaging (MRI) for different tasks related to the management of patients with hepatocellular carcinoma (HCC). However, its implementation in clinical practice is still far, with many issues related to the methodological quality of radiomic studies. To systematically review the current status of MRI radiomic studies concerning HCC using the Radiomics Quality Score (RQS). A systematic literature search of PubMed, Google Scholar, and Web of Science databases was performed to identify original articles focusing on the use of MRI radiomics for HCC management published between 2017 and 2023. The methodological quality of radiomic studies was assessed using the RQS tool. Spearman's correlation (ρ) analysis was performed to explore if RQS was correlated with journal metrics and characteristics of the studies. The level of statistical signi-ficance was set at P < 0.05. One hundred and twenty-seven articles were included, of which 43 focused on HCC prognosis, 39 on prediction of pathological findings, 16 on prediction of the expression of molecular markers outcomes, 18 had a diagnostic purpose, and 11 had multiple purposes. The mean RQS was 8 ± 6.22, and the corresponding percentage was 24.15% ± 15.25% (ranging from 0.0% to 58.33%). RQS was positively correlated with journal impact factor (IF; ρ = 0.36, P = 2.98 × 10-5), 5-years IF (ρ = 0.33, P = 1.56 × 10-4), number of patients included in the study (ρ = 0.51, P < 9.37 × 10-10) and number of radiomics features extracted in the study (ρ = 0.59, P < 4.59 × 10-13), and time of publication (ρ = -0.23, P < 0.0072). Although MRI radiomics in HCC represents a promising tool to develop adequate personalized treatment as a noninvasive approach in HCC patients, our study revealed that studies in this field still lack the quality required to allow its introduction into clinical practice.

The role of IL-36 and 37 in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) has garnered considerable attention due to its morbidity and mortality. Although the precise mechanisms underlying HCC tumorigenesis remain to be elucidated, evidence suggests that host immunity plays a pivotal role in its development. IL-36 and IL-37 are important immunoregulatory cytokines classified as pro-inflammatory and anti-inflammatory respectively. In the context of HCC, the downregulation of intrahepatic IL-36 is inversely correlated with cirrhosis, but positively correlated with 5-year survival rates, suggesting that IL-36 offers protection during HCC development. However, IL-36 may lose its hepatoprotective effects as the disease progresses to HCC in the context of dysregulated immunity in cirrhotic patients. Substantially increased circulating IL-36 in HCC patients is likely a systemic response to HCC stimulation, but is insufficient to suppress progression towards HCC. Intrahepatic IL-37 is suppressed in HCC patients, consistent with the inverse correlation between intrahepatic IL-37 and the level of AFP in HCC patients, suggesting IL-37 exerts hepatoprotection. There is no significant difference in IL-37 among differentiations of HCC or with respect to clinical BCLC stages or cirrhosis status in HCC patients. However, IL-37 protection is demonstrated in an IL-37 transfected HCC animal model, showing significantly reduced tumour size. IL-36/37 may inhibit HCC by enhancing M1 tumour-associated macrophages while not affecting M2 macrophages. The interplay between IL-36 (pro-inflammatory) and IL-37 (anti-inflammatory) is emerging as a crucial factor in host protection against the development of HCC. Further research is needed to investigate the complex mechanisms involved and the therapeutic potential of targeting these cytokines in HCC management.

NQO1 Mediates Lenvatinib Resistance by Regulating ROS-induced Apoptosis in Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is the third leading cause of cancer-associated death worldwide. As a first-line drug for advanced HCC treatment, lenvatinib faces a significant hurdle due to the development of both intrinsic and acquired resistance among patients, and the underlying mechanism remains largely unknown. The present study aims to identify the pivotal gene responsible for lenvatinib resistance in HCC, explore the potential molecular mechanism, and propose combinatorial therapeutic targets for HCC management. Cell viability and colony formation assays were conducted to evaluate the sensitivity of cells to lenvatinib and dicoumarol. RNA-Seq was used to determine the differences in transcriptome between parental cells and lenvatinib-resistant (LR) cells. The upregulated genes were analyzed by GO and KEGG analyses. Then, qPCR and Western blotting were employed to determine the relative gene expression levels. Afterwards, the intracellular reactive oxygen species (ROS) and apoptosis were detected by flow cytometry. PLC-LR and Hep3B-LR were established. There was a total of 116 significantly upregulated genes common to both LR cell lines. The GO and KEGG analyses indicated that these genes were involved in oxidoreductase and dehydrogenase activities, and reactive oxygen species pathways. Notably, NAD(P)H:quinone oxidoreductase 1 (NQO1) was highly expressed in LR cells, and was involved in the lenvatinib resistance. The high expression of NQO1 decreased the production of ROS induced by lenvatinib, and subsequently suppressed the apoptosis. The combination of lenvatinib and NQO1 inhibitor, dicoumarol, reversed the resistance of LR cells. The high NQO1 expression in HCC cells impedes the lenvatinib-induced apoptosis by regulating the ROS levels, thereby promoting lenvatinib resistance in HCC cells.

Formulation of lactoferrin decorated dextran based chitosan-coated europium metal-organic framework for targeted delivery of curcumin

Hepatocellular carcinoma (HPTC) currently ranks as the third leading cause of cancer-related mortality, necessitating an advanced formulation strategy. Recently, lactoferrin (Lf) has been utilized as a specific targeting ligand in HPTC due to its high specificity towards the asialoglycoprotein receptor expressed in cancer cells. Therefore, we present the fabrication of an Lf-decorated carboxymethyl dextran-encased chitosan-coated europium metal-organic framework-based nanobioconjugate (Lf-CMD-CS-CUR@Eu-MOF) for targeted curcumin (CUR) delivery. Briefly, CUR was loaded into Eu-MOF, followed by coating cationic ‘CS’ on the CUR@Eu-MOF surface. Simultaneously, Lf-decorated CMD was prepared via an esterification reaction. Subsequently, Lf-CMD-CS-CUR@Eu-MOF was synthesized using the Maillard reaction. Various spectral characterizations, drug entrapment, drug content, in vitro drug release, biocompatibility and cell cytotoxicity studies were performed. It exhibited an entrapment efficiency of 88.87 ± 2.1 %, a drug content of 3.45 ± 0.98 %, and a drug loading rate of 34.85 ± 0.6 mg/g. Furthermore, the Lf-CMD-CS-CUR@Eu-MOF exhibits excellent biocompatibility with normal cells. The in vitro dissolution study confirmed a release of 78.12 % of ‘CUR’ in pH 5.8 phosphate buffer (over 120 h), attributed to the controlled release rate by the ‘CS’ coating on the surface of CUR@Eu-MOF. The BEL-7402 cell line showed concentration-dependent toxicity of nanobioconjugate to cancerous cells. Therefore, when ‘Lf’ is surface-decorated onto an appropriate polymeric material, it gains the capability to function as a carrier for transporting ‘CUR’ to the precise target site within HPTC. In conclusion, Lf-CMD incorporated CS-coated Eu-MOF can provide a promising approach for targeted drug delivery in HPTC management.

SLC7A11 in hepatocellular carcinoma: potential mechanisms, regulation, and clinical significance.

Exploring novel early detection biomarkers and developing more efficacious treatments remain pressing tasks in the current research landscape for hepatocellular carcinoma (HCC). Morphologically and molecularly separate from apoptosis, cell death, and autophagy, ferroptosis is a recently discovered, unique, controlled form of cell death. SLC7A11 (also known as xCT) represents a subunit of the cystine-glutamate antiporter (also known as system Xc(-)). A growing body of research suggests that induction of ferroptosis through SLC7A11 can effectively eliminate hepatocellular carcinoma (HCC) cells, particularly those exhibiting resistance to alternative forms of cell death. Thus, targeting ferroptosis via SLC7A11 may become a new direction for the design of therapeutic strategies for HCC. Although many research articles have investigated the possible roles of SLC7A11 in HCC, a study that summarizes the main findings, including the regulators and mechanisms of action of SLC7A11 in HCC is not available. Therefore, we present a comprehensive overview of the functions of ferroptosis, particularly SLC7A11, in the identification, development, and management of HCC in this review. In addition, we discuss how this knowledge can be translated into treatment by providing a systemic therapy in advanced HCC using sorafenib, the first-line drug targeting multiple kinases and SLC7A11. We further dissect the possible barriers as well as the corresponding solutions and provide insights on how to navigate effective treatment using this knowledge.

Efficacy and features of balloon-occluded transarterial chemoembolization for hepatocellular carcinoma: a narrative review.

Systemic therapy for hepatocellular carcinoma (HCC) is recommended in transarterial chemoembolization (TACE)-refractory and unsuitable cases. In Japan, TACE is broadly classified into conventional TACE (C-TACE), balloon occluded TACE (B-TACE), and drug-eluting beads TACE. However, the type of TACE recommended for TACE-refractory or unsuitable cases has not been elucidated, and a targeted approach for individual cases and appropriate TACE selection is important. B-TACE is considered a valuable therapeutic option in the management of HCC. The technique involves the precise placement of a microcatheter with a balloon into the target hepatic artery, followed by selective occlusion of the hepatic artery, including tumor-feeding vessels, using the balloon. By leveraging the hemodynamic changes resulting from arterial occlusion, B-TACE enables effective accumulation of chemotherapeutic agents within the tumor. Incorporating B-TACE into the treatment strategy for HCC is of utmost importance. Therefore, this article provides an overview of the technique. A comprehensive review of all available literature in the English language through December 1, 2023 utilizing PubMed was conducted. In the intermediate stage, TACE and systemic therapy play complementary roles, and it is important to select a treatment strategy that considers tumor status and hepatic reserve. However, no study has investigated the various types of TACE in the treatment of such patients. Currently, TACE in Japan is broadly classified into C-TACE, B-TACE, and drug-eluting beads TACE (DEB-TACE). This article outlines the evolution of B-TACE for HCC. We identified retrospective and prospective studies evaluating B-TACE. In this review, we evaluate data on B-TACE for HCC. In the era of systemic therapy, B-TACE may play a complementary and synergy effect role.

Diagnostic value of Midkine and AFP in the detection of hepatocellular carcinoma: A systematic review and meta-analysis.

Hepatocellular carcinoma (HCC) posed significant health problems and deaths. There are various challenges in the management of HCC, including the late detection or diagnosis. The ongoing diagnostic method in HCC also hinders the detection on the early stages of the disease, thus biomarkers need to be explored further for HCC detection. Serum alpha fetoprotein (AFP) and Midkine (MDK) are two proteins which might be the biomarker of choice in the detection of HCC. This meta-analysis aims to analyze the accuracy of Midkine and AFP in the detection of HCC. The systematic review and meta-analysis was conducted by adhering to the Preferred Reporting System for Systematic Review and Meta-Analysis (PRISMA) guidelines. We conduct literature screening and selection followed by quality assessment from various databases such as PubMed, MEDLINE, SpringerLink, ProQuest, EBSCOhost, Cochrane, and EMBASE. The included studies were then extracted and analyzed cumulatively using MedCalc and MetaDTA with forest plot and ROC curve as outcome. 12 studies were included in this study. The AFP biomarker yields sensitivity value of 62.5% (97.5% CI 0.442 - 0.778) and specificity value of 95% (97.5% CI 0.842 - 0.986), while the Midkine biomarker denotes sensitivity value of 91.6% (97.5% CI 0.83 - 0.961) and specificity value of 82.2% (97.5% CI 0.83 - 0.96). Both AFP and MDK are proven to be a good diagnostic tool or biomarker in the detection of HCC. The use of both in combination should provide high quality diagnostic marker for HCC suspected patients. Further studies on this should be conducted.

Biomarkers for Hepatocellular Carcinoma: Diagnosis, Prognosis, and Treatment Response Assessment - A Systematic Review

Background: Hepatocellular carcinoma (HCC) is a significant global health concern due to its high mortality rates, highlighting the urgent need for improved diagnostic, prognostic, and therapeutic markers. Biomarkers hold potential for enhancing the early detection, prognostic evaluation, and treatment response assessment of HCC. Methods: A systematic review was conducted to evaluate the utility of various biomarkers in the diagnosis, prognosis, and prediction of treatment responses in HCC. A comprehensive search was performed in electronic databases, including PubMed, Embase, Scopus, and the Cochrane Library, up to January 2024. Studies that assessed biomarkers for HCC in terms of diagnostic accuracy, prognostic value, or their role in predicting treatment responses were included. Data extraction and quality assessment were performed for all eligible studies. Results: The search initially identified 78 articles, of which 41 met the inclusion criteria. The review evaluated biomarkers from genomic, epigenomic, transcriptomic, proteomic, and metabolomic sources. The diagnostic accuracy of these biomarkers ranged from 70% to 90%, with alpha-fetoprotein (AFP) being the most frequently studied and widely utilized biomarker. Prognostic biomarkers were found to have significant associations with overall survival and disease-free survival. Biomarkers predicting treatment responses, particularly to sorafenib and immunotherapy, exhibited varying levels of sensitivity and specificity. Conclusion: Biomarkers play a critical role in the management of HCC, offering promising potential for early diagnosis, prognostic assessment, and prediction of treatment responses. However, further validation and standardization of these biomarkers are required before they can be implemented clinically. Future research should aim to identify and integrate novel biomarkers within a multidisciplinary framework to enable personalized management of HCC.

Comprehensive Review of Hepatocellular Carcinoma: Epidemiological Trends, Risk Factors, and Mechanisms of Carcinogenesis

Background: Hepatocellular carcinoma (HCC) is a leading cause of cancer-related deaths worldwide, often arising in the context of chronic liver diseases like cirrhosis, with significant contributions from hepatitis B virus (HBV), hepatitis C virus (HCV), and metabolic dysfunction-associated fatty liver disease (MAFLD). The disease’s high mortality rate and complex etiology underscore the need for improved diagnostic and therapeutic strategies. Methods: This review synthesizes current epidemiological data and research on HCC. We analyzed global and regional incidence and mortality rates, assessed the role of major risk factors, including HBV, HCV, and MAFLD, and evaluated recent advancements in diagnostic and therapeutic approaches. Data were sourced from recent literature, including epidemiological studies and clinical trials. Results: The incidence of HCC continues to rise globally, with significant regional variations. HBV and HCV infections remain major contributors to HCC, with HBV's integration into the host genome playing a critical role in carcinogenesis. MAFLD, now a prominent risk factor in high-income countries, is expected to impact global HCC rates increasingly. Despite advances in diagnostic techniques such as precision medicine and liquid biopsies, early detection remains challenging, and recurrence rates after treatment are high. Conclusion: The growing burden of HCC highlights the urgent need for enhanced screening methods and novel treatments. Continued research into the disease’s etiology and improved therapeutic approaches are essential to reducing incidence and improving patient outcomes. Enhanced early detection and personalized treatment strategies are critical to addressing the ongoing challenges in HCC management.

HMGB2 drives tumor progression and shapes the immunosuppressive microenvironment in hepatocellular carcinoma: insights from multi-omics analysis.

Hepatocellular carcinoma (HCC) poses a significant health burden globally, with high mortality rates despite various treatment options. Immunotherapy, particularly immune-checkpoint inhibitors (ICIs), has shown promise, but resistance and metastasis remain major challenges. Understanding the intricacies of the tumor microenvironment (TME) is imperative for optimizing HCC management strategies and enhancing patient prognosis. This study employed a comprehensive approach integrating multi-omics approaches, including single-cell RNA sequencing (scRNA-seq), bulk RNA sequencing (Bulk RNA-seq), and validation in clinical samples using spatial transcriptomics (ST) and multiplex immunohistochemistry (mIHC). The analysis aimed to identify key factors influencing the immunosuppressive microenvironment associated with HCC metastasis and immunotherapy resistance. HMGB2 is significantly upregulated in HCCTrans, a transitional subgroup associated with aggressive metastasis. Furthermore, HMGB2 expression positively correlates with an immunosuppressive microenvironment, particularly evident in exhausted T cells. Notably, HMGB2 expression correlated positively with immunosuppressive markers and poor prognosis in HCC patients across multiple cohorts. ST combined with mIHC validated the spatial expression patterns of HMGB2 within the TME, providing additional evidence of its role in HCC progression and immune evasion. HMGB2 emerges as a critical player of HCC progression, metastasis, and immunosuppression. Its elevated expression correlates with aggressive tumor behavior and poor patient outcomes, suggesting its potential as both a therapeutic target and a prognostic indicator in HCC management.

ST8SIA6-AS1, a novel lncRNA star in liver cancer.

Liver cancer is one of the most lethal gastrointestinal malignancies. Emerging evidence has underscored the pivotal role of long non-coding RNAs (lncRNAs) in tumorigenesis, with ST8SIA6-AS1 identified as a novel oncogenic lncRNA contributing to liver cancer progression. ST8SIA6-AS1 is consistently upregulated in hepatic cancer tissues and is strongly associated with unfavorable prognosis. Moreover, it demonstrates high diagnostic efficacy in detecting HCC. ST8SIA6-AS1 is involved in various cellular processes including proliferation, migration, and invasion, primarily through its function as a competing endogenous RNA (ceRNA), thereby facilitating hepatocarcinogenesis and disease advancement. This review provides a detailed examination of the molecular functions and regulatory mechanisms of ST8SIA6-AS1 in hepatocellular carcinoma (HCC) and highlights its potential as a promising biomarker for liver cancer, aiming to propel the development of innovative therapeutic strategies for HCC management.

Bulk- and single cell-RNA sequencing reveal KIF20A as a key driver of hepatocellular carcinoma progression and immune evasion.

Kinesin family member 20A (KIF20A) is essential for cell proliferation and is implicated in promoting tumor progression, but its role in hepatocellular carcinoma (HCC) remains poorly studied. Through the analysis of bulk RNA-sequencing (bulk RNA-seq) and single-cell RNA sequencing (scRNA-seq) data, the expression of KIF20A and its relationship with diagnosis, prognosis, and the immune microenvironment were examined. The association between KIF20A and the malignant progression and metastasis of HCC was confirmed through in vitro and in vivo experiments. Furthermore, patient re-staging was performed using Recursive Partitioning Analysis (RPA) to enhance clinical benefit. In this study, we firstly found KIF20A was overexprerssed in HCC both by bulk RNA-seq and scRNA-seq, and then the overexpression of KIF20A significantly promoted the proliferation, invasion, and metastasis in vitro. In vivo, the overexpression of KIF20A promoted the growth and lung metastasis of HCC. Furthermore, gene set variation analysis of bulk RNA-seq and scRNA-seq revealed that KIF20A might be associated with cell cycle related signaling pathways of E2F and G2M, and overexpression of KIF20A inhibited the activity of p21 and bax, as well as shortened G2 phase. Importantly, we found that KIF20A could induce T cell exhaustion via the SPP1-CD44 axe using scRNA-seq. Additionally, KIF20A was also correlated with the expression of immune checkpoint inhibitors (ICIs), and KIF20Ahigh subgroup might be benefited from the ICIs therapy. KIF20A emerges as a pivotal driver of HCC progression, intricately regulating cell cycle pathways and modulating immune responses, which position KIF20A as a promising target for HCC management.

MRI monitoring of combined therapy with transcatheter arterial delivery of NK cells and systemic administration of sorafenib for the treatment of HCC.

This preclinical study explored the synergistic potential of sorafenib and NK cell chemoimmunotherapy to combat hepatocellular carcinoma (HCC) in a rat model. We aimed to enhance NK cell cytotoxicity through IL-12/18 cytokines supplementation and elucidate the underlying molecular mechanisms driving this collaborative antitumor action. Twenty-four Sprague-Dawley rats were divided into distinct treatment groups, receiving sorafenib via gavage and NK cells via catheterization of the proper hepatic artery. Tumor growth and treatment response were monitored through weekly MRI scans, including T1w, T2w, DCE, and DWI sequences. Histological examinations assessed tumor cell viability, apoptosis fraction, and microvessel density. The combined therapy demonstrated significant inhibition of tumor growth, angiogenesis, and induction of durable antitumor immunity compared to either modality alone. DCE-MRI and DWI revealed distinct alterations in tumor microvasculature, highlighting the effectiveness of the combination. Our findings highlight the promise of sorafenib-augmented NK cell chemoimmunotherapy as a potential therapeutic strategy for HCC management. The targeted delivery of IL-12/18 cytokines supplemented NK cells effectively enhanced cytotoxicity within the tumor microenvironment, leading to improved antitumor responses. Further investigation in clinical trials is warranted to validate these findings in human patients and explore the translational potential of this approach.

Prevalence of HCC among Living Donor Liver Transplant Recipients and Effect on Outcome Georgian Experience

: Liver transplantation (LT) may be the best curative treatment that offers a chance of cure for the tumor and the underlying cirrhosis by complete extirpation of both. Hepatocellular Carcinoma (HCC) is a formidable global health challenge, representing one of the most prevalent primary liver malignancies with increasing incidence rates worldwide. It sets the stage for a comprehensive exploration of how LDLT has redefined the paradigms of treatment for HCC and contributed to enhanced patient outcomes. To answer the question of this paper we used cross sectional study design among 84 Living Donor Liver Transplant Recipients. After collecting data analyzing patient’s medical cards we have found that out of 84 recipients 12 (11%) had a Hepatocellular Carcinoma, out of this 8 (6.7%) recipients dead and 4 (3.3%) is alive. We may have challenges such as: Diagnostic Challenges, Treatment Options, and Selection Criteria for LDLT in HCC. The relationship between HCC and LDLT is a dynamic and evolving field. LDLT has significantly expanded the therapeutic options for selected HCC patients, offering hope for improved outcomes. However, the intricate interplay between patient selection, surgical techniques, and post-transplant care underscores the importance of a multidisciplinary approach to HCC management. Ongoing research and advances in both HCC treatment and LDLT continue to shape the landscape of this complex disease and transplantation strategy.&#x0D;

OMA1 and YME1L as a Diagnostic Panel in Hepatocellular Carcinoma.

Identifying new hepatocellular carcinoma (HCC)-driven signaling molecules and discovering their molecular mechanisms are crucial for efficient and better outcomes. Recently, OMA1 and YME1L, the inner mitochondrial proteases, were displayed to be associated with tumor progression in various cancers; however, their role in HCC has not yet been studied. Therefore, we evaluated the possible role of OMA1/YME1L in HCC staging and discussed their potential role in cellular apoptosis and proliferation. Our study was performed using four groups of male albino rats: a normal control and three diethyl nitrosamine-treated groups for 8, 16, and 24 weeks. The OMA1 and YME1L, matrix-metalloproteinase-9 (MMP-9), and cyclin D1 content were measured in liver tissues, while alpha-fetoprotein (AFP) level was assessed in serum. Additionally, Ki-67 expression was evaluated by immunohistochemistry. The relative hepatic expression of Bax, and tissue inhibitor matrix metalloproteinase (TIMP-3) was measured. Herein, we confirmed for the first time that OMA1 is down-regulated while YME1L is up-regulated in HCC in the three studied stages with subsequent inhibition of apoptosis and cell cycle progression. Furthermore, these proteases have a possible role in metastasis. These newly recognized results suggested OMA1 and YME1L as possible diagnostic tools and therapeutic targets for HCC management.