Hepatocellular Carcinoma In Recent Years Research Articles

Advances in the Pathogenesis of Metabolic Liver Disease-Related Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is the sixth most common cancer globally and the primary cause of death in cancer cases, with significant public health concern worldwide. Despite the overall decline in the incidence and mortality rates of HCC in recent years in recent years, the emergence of metabolic liver disease-related HCC is causing heightened concern, especially in countries like the United States, the United Kingdom, and P.R. China. The escalation of metabolic liver disease-related HCC is attributed to a combination of factors, including genetic predisposition, lifestyle choices, and changes in the living environment. However, the pathogenesis of metabolic liver disease-associated HCC remains imperfect. In this review, we encapsulate the latest advances and essential aspects of the pathogenesis of metabolic liver disease-associated HCC, including alcoholic liver disease (ALD), metabolic dysfunction-associated steatotic liver disease (MASLD), and inherited metabolic liver diseases.

Real-world experience and outcomes of hepatocellular carcinoma (HCC) treated with transarterial radioembolization (TARE).

463 Background: TARE has been the preferred choice of locoregional therapy to advanced HCC in recent years. We attempted to identify factors contributing to the success of TARE in this retrospective review. Methods: HCC patients who received at least one TARE between 1/1/2015 and 8/30/22 at Ohio State University were included in this study. The patient's baseline characteristics at diagnosis (BLC) were extracted by chart review with post-procedural complications and survival outcomes. Descriptive statistics and log-rank test for survival outcomes were conducted using JMP Pro 16 (SAS Institute Inc., Cary, NC). Results: Our cohort had 144 patients with median age of diagnosis (dx) of 65 years, 81 % Caucasians, 81% males, 5% and 51% with hepatitis B and C, respectively; 24% and 21% ascites (As) and hepatic encephalopathy (HE) at dx, respectively; 72% (n=125) had just one procedure (24 had two planned procedures which were considered as 1), 12% (17) and 1% (2) had second and third procedures for recurrence, respectively. Immune checkpoint inhibitor (ICI) and other systemic therapy (tyrosine kinase inhibitor (TKI) or ramucirumab (Ram)) were given to 27% (5 before and 34 after TARE) and 24% (5 before and 30 after TARE), respectively. Other HCC-related BLC includes the number of lesions 1 vs 2-3 vs multiple = 45% vs 33% vs 22%; single lobe vs two lobes = 66 vs 33%; portal vein tumor thrombosis (PVTT) = in main portal vein vs. non-main veins (left or right or lower level) vs no PVTT = 14% vs 10% vs 76%. Median overall survival (OS) and time to recurrence after the first TARE (TTR) were 11 and 4 months (m), respectively. The only BLC that significantly influenced TTR was As (3 vs 4 m, p=0.008). Factors impacting OS were discussed in the table. Follow-up imaging (median = 3m) was available for response evaluation in 107/144 (indeterminate response (IR) reported in 25), and the response noted was reflective of OS (objective response vs. disease progression vs indeterminate, 22 vs 6 vs 8.5 m, p<0.001). Conclusions: Careful patient selection based on BLC and the use of ICI (before or after) could improve the outcomes in HCC patients treated with TRAE. Larger prospective studies are needed to validate the study. [Table: see text]

A facile boronophenylalanine modified polydopamine dual drug-loaded nanoparticles for enhanced anti-tumor immune response in hepatocellular carcinoma comprehensive treatment

Hepatocellular carcinoma (HCC) has an insidious onset and high malignancy. Most patients have progressed to intermediate and advanced stages by the time of diagnosis, and the long-term efficacy of traditional treatments is not satisfactory. Immunotherapy has shown great promise in the treatment of HCC in recent years; however, the low immunogenicity and severe immunosuppressive tumor microenvironment result in a low response rate to immunotherapy in HCC patients. Therefore, it is of great significance to improve the immunogenicity of HCC and thus enhance its sensitivity to immunotherapy. Here, we prepared the boronophenylalanine-modified dual drug-loaded polydopamine nanoparticles by a facile method. This system used boronophenylalanine-modified polydopamine nanoparticles as a delivery vehicle and photothermal material for the chemotherapeutic drug doxorubicin and the immune agonist CpG oligodeoxynucleotides (CpG-ODN), with both active targeting and lysosomal escape functions. The cancer cells are rapidly killed by photothermal treatment, and then chemotherapy is used to further kill cancer cells that are inadequately treated by photothermal treatment. The combination of photothermal-chemotherapy synergistically induces the release of relevant antigens from tumor cells, thus initiating anti-tumor immunity; and then cooperates with CpG-ODN to trigger a powerful anti-tumor immune memory effect, potently and durably inhibiting HCC recurrence.

The double-edged sword role of hydrogen sulfide in hepatocellular carcinoma.

With an increasing worldwide prevalence, hepatocellular carcinoma (HCC) is the most common primary malignant tumor of the liver in the world. It is also the primary reason for cancer-related death in the world. The pathogenesis of HCC is complex, such as DNA methylation changes, immune regulatory disorders, cell cycle disorders, chromosomal instability, and so on. Although many studies have been conducted on HCC, the molecular mechanisms of HCC are not completely understood. At present, there is no effective treatment for HCC. Hydrogen sulfide (H2S) has long been regarded as a toxic gas with the smell of rotten eggs, but recent studies have shown that it is an important gasotransmitter along with carbon monoxide (CO) and nitric oxide (NO). Increasing evidence indicates that H2S has multiple biological functions, such as anti-inflammation, anti-apoptosis, anti-oxidative stress, and so on. Recently, a lot of evidence has shown that H2S has a "double-edged sword" effect in HCC, but the mechanism is not fully understood. Here, we reviewed the progress on the role and mechanism of H2S in HCC in recent years, hoping to provide a theoretical reference for future related research.

Little things with significant impact: miRNAs in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) has developed into one of the most lethal, aggressive, and malignant cancers worldwide. Although HCC treatment has improved in recent years, the incidence and lethality of HCC continue to increase yearly. Therefore, an in-depth study of the pathogenesis of HCC and the search for more reliable therapeutic targets are crucial to improving the survival quality of HCC patients. Currently, miRNAs have become one of the hotspots in life science research, which are widely present in living organisms and are non-coding RNAs involved in regulating gene expression. MiRNAs exert their biological roles by suppressing the expression of downstream genes and are engaged in various HCC-related processes, including proliferation, apoptosis, invasion, and metastasis. In addition, the expression status of miRNAs is related to the drug resistance mechanism of HCC, which has important implications for the systemic treatment of HCC. This paper reviews the regulatory role of miRNAs in the pathogenesis of HCC and the clinical applications of miRNAs in HCC in recent years.

Evaluating treatment response following locoregional therapy for hepatocellular carcinoma: A review of the available serological and radiological tools for assessment

Hepatocellular carcinoma (HCC) is an aggressive primary malignancy of the liver and is the third most common cause of cancer-related global mortality. There has been a steady increase in treatment options for HCC in recent years, including innovations in both curative and non-curative therapies. These advances have brought new challenges and necessary improvements in strategies of disease monitoring, to allow early detection of HCC recurrence. Current serological and radiological strategies for post-treatment monitoring and prognostication and their limitations will be discussed and evaluated in this review.

Advancements in Hepatocellular Carcinoma: Potential Preclinical Drugs and Their Future.

Hepatocellular carcinoma (HCC) is one of the foremost causes of tumor-affiliated demises globally. The HCC treatment has undergone numerous developments in terms of both drug and non-drug treatments. The United States Food and Drug Administration (FDA) has authorized the usage of a variety of drugs for the treatment of HCC in recent years, involving multi-kinase inhibitors (lenvatinib, regorafenib, ramucirumab, and cabozantinib), immune checkpoint inhibitors (ICIs) (pembrolizumab and nivolumab), and combination therapies like atezolizumab along with bevacizumab. There are currently over a thousand ongoing clinical and pre-clinical studies for novel HCC drugs, which portrays a competent setting in the field. This review discusses the FDA-approved HCC drugs, their molecular targets, safety profiles, and potential disadvantages; ii. The in-trial agents/drugs, their molecular targets, and possible benefits compared to alternatives, and iii-the current and future status of potential preclinical drugs with novel therapeutic targets for HCC. Consequently, existing drug treatments and novel strategies with their balanced consumption could ensure a promising future for a universal remedy of HCC in the near future.

Sorafenib combined with STAT3 knockdown triggers ER stress-induced HCC apoptosis and cGAS-STING-mediated anti-tumor immunity

Sorafenib is the first-line treatment for advanced hepatocellular carcinoma (HCC). However, it is difficult to alleviate this disease process using single-agent chemotherapy. Using combination therapies for advanced HCC has become a major trend. Given that STAT3 overexpression is involved in chemotherapy resistance and the immune escape of HCC cells, it has become a potential therapeutic target for HCC in recent years. GEO database analysis showed that STAT3 levels in tumor tissues from non-responders were significantly higher than those in responders to sorafenib. Our studies demonstrated that STAT3 knockdown promoted sorafenib-induced ER stress-induced apoptosis. Importantly, the DNA released by dead HCC cells stimulated the cGAS-STING signaling pathway in CD103+ DCs and promoted type I interferon production, thus, enhancing the anti-tumor function of CD8+ T and NK cells. In conclusion, our results revealed that the combination strategy of sorafenib and STAT3 knockdown might be a potential treatment strategy for HCC, directly and efficiently disturbing the tumor features of HCC cells while improving the tumor microenvironment via the cGAS-STING-Type I IFNs axis of DCs, inducing anti-HCC immune responses.

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.

Nanotechnology strategies for hepatocellular carcinoma diagnosis and treatment.

Hepatocellular carcinoma (HCC) is a common malignancy threatening human health, and existing diagnostic and therapeutic techniques are facing great challenges. In the last decade or so, nanotechnology has been developed and improved for tumor diagnosis and treatment. For example, nano-intravenous injections have been approved for malignant perivascular epithelioid cell tumors. This article provides a comprehensive review of the applications of nanotechnology in HCC in recent years: (I) in radiological imaging, magnetic resonance imaging (MRI), fluorescence imaging (FMI) and multimodality imaging. (II) For diagnostic applications in HCC serum markers. (III) As embolic agents in transarterial chemoembolization (TACE) or directly as therapeutic drugs. (IV) For application in photothermal therapy and photodynamic therapy. (V) As carriers of chemotherapeutic drugs, targeted drugs, and natural plant drugs. (VI) For application in gene and immunotherapy. Compared with the traditional methods for diagnosis and treatment of HCC, nanoparticles have high sensitivity, reduce drug toxicity and have a long duration of action, and can also be combined with photothermal and photodynamic multimodal combination therapy. These summaries provide insights for the further development of nanotechnology applications in HCC.

Cholesterol Metabolism: A Double-Edged Sword in Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) represents a leading cause of cancer-related deaths globally. The rising incidence of metabolic syndrome and its hepatic manifestation, nonalcoholic fatty liver disease (NAFLD), have emerged as the fastest-growing cause of HCC in recent years. Cholesterol, a major lipid component of the cell membrane and lipoprotein particles, is primarily produced and metabolized by the liver. Numerous studies have revealed an increased cholesterol biosynthesis and uptake, reduced cholesterol exportation and excretion in HCC, which all contribute to lipotoxicity, inflammation, and fibrosis, known HCC risk factors. In contrast, some clinical studies have shown that higher cholesterol is associated with a reduced risk of HCC. These contradictory observations imply that the relationship between cholesterol and HCC is far more complex than initially anticipated. Understanding the role of cholesterol and deciphering the underlying molecular events in HCC development is highly relevant to developing new therapies. Here, we discuss the current understanding of cholesterol metabolism in the pathogenesis of NAFLD-associated HCC, and the underlying mechanisms, including the roles of cholesterol in the disruption of normal function of specific cell types and signaling transduction. We also review the clinical progression in evaluating the association of cholesterol with HCC. The therapeutic effects of lowering cholesterol will also be summarized. We also interpret reasons for the contradictory observations from different preclinical and human studies of the roles of cholesterol in HCC, aiming to provide a critical assessment of the potential of cholesterol as a therapeutic target.

Impact of Sarcopenia as a Prognostic Factor on Reductive Hepatectomy for Advanced Hepatocellular Carcinoma.

Sarcopenia has been reported to be a significant prognostic factor in patients with hepatocellular carcinoma in recent years. This study aimed to clarify the prognostic significance of sarcopenia in advanced hepatocellular carcinoma treated with reductive hepatectomy. We retrospectively analyzed 93 patients who underwent reductive hepatectomy for advanced hepatocellular carcinoma. Median survival time of the sarcopenia group (16.4 months) was significantly shorter than that of the non-sarcopenia group (20.4 months). The overall survival rates at 1, 3, and 5 years of the sarcopenia group were significantly lower than those of the non-sarcopenia group (57.9%, 8.6%, and 2.9% vs. 67.3%, 29.2%, and 15.7%, respectively; p=0.035). On multivariate analysis, sarcopenia was a significant risk factor of overall survival (hazard ratio=1.60, 95% confidence interval=1.00-2.56, p=0.049). Sarcopenia was a significant prognostic factor of survival after reductive hepatectomy in advanced hepatocellular carcinoma.

Immune Checkpoint Inhibitors in Hepatocellular Carcinoma: Current Progresses and Challenges.

Hepatocellular carcinoma (HCC) is one of the most common malignant tumor in the world and its incidence is increasing in many countries. In recent years, with the deepening understanding of the immune and pathological mechanisms of HCC, immunotherapy based on the regulation of tumor immune microenvironment has become a new treatment choice for patients with HCC. Immune checkpoint inhibitors (ICIs) targeting programmed death protein-1, programmed death protein-ligand-1, or cytotoxic T-lymphocyte-associated antigen 4 are the most widely used. Instead of general immune-enhancing therapies, ICIs can reactivate anti-tumor immune responses by disrupting co-inhibitory T cell signaling. In this review, the research progress and existing problems of ICIs in the treatment of HCC in recent years are reviewed.

Advances and controversies of statins application in prevention and treatment of hepatocellular carcinoma

Statins, as lipid-regulating drugs, have been widely used in the treatment for hyperlipidemia and the primary and secondary prevention of cardio-cerebrovascular diseases. Hepatocellular carcinoma (HCC) is a serious burden of liver disease in China with poor prognosis, thus effective adjuvant drug used for HCC treatment has attracted much attention. Statins can suppress tumor growth, decrease the risk of tumorigenesis and postoperative recurrence of HCC, extend the survival time and improve the therapeutic effect of other treatment, therefore might increase the benefit obtained by the HCC patients. Statins also can impact the expression of MAPK/ERK signaling pathway, promote the apoptosis of malignant cells and ameliorate the HCC risk of hepatitis B virus infected patients. Statins not only prevents the HCC, but also has part therapeutic effect on the different stage of HCC. Although it can't replace the operation, radiofrequency ablation, molecular targeted treatment and immunotherapy currently, statins may be a potential adjuvant drug to provide clinical benefit for HCC patients. The advancement of statins application in the prevention and treatment of HCC has attracted more attention recently, however, discussion and controversy also existed about whether it can eventually become an adjuvant therapy for HCC. The purpose of this paper is to summarize and comment on the new development and disputes of statins application in the prevention and treatment of HCC in recent years, to provide help for the future clinical practice.

MicroRNA in HCC: Biomarkers and Therapeutic Targets

Hepatocellular carcinoma (HCC) is a malignant tumor with high morbidity and mortality. At present, diagnostic methods such as imaging observation, serum testing and tissue biopsy, as well as treatment methods such as surgical resection, radiotherapy, and chemotherapy have certain limitations in clinical interventions for HCC due to the complex pathogenesis and drug resistance of liver cancer, which seriously affect the survival and prognosis of patients. As a large-scale cytokine, microRNA (miRNA) plays an important role in regulating various life activities of cells. Extensive evidence proved that certain miRNAs are specifically expressed in the tissues and blood of HCC patients, and some of them have been confirmed as important factors that can participate in the regulation of key signaling pathways in cancer cells. For this reason, these miRNAs have great potential in clinical diagnosis and treatment of HCC, and can improve the limitations of conventional diagnosis and treatment. Our paper reviews the research on miRNA biomarkers and targets in HCC in recent years, and aims to provide new ideas for the diagnosis and treatment of HCC.

Research Progresses of Targeted Therapy and Immunotherapy for Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors worldwide, with nearly one million new cases and deaths every year. Owing to the complex pathogenesis, hidden early symptoms, rapidly developing processes, and poor prognosis, the morbidity and mortality of HCC are increasing yearly. With the progress being made in modern medicine, the treatment of HCC is no longer limited to traditional methods. Targeted therapy and immunotherapy have emerged to treat advanced and metastatic HCC in recent years. Since Sorafenib is the first molecular targeting drug against angiogenesis, targeted drugs for HCC are continually emerging. Moreover, immunotherapy plays a vital role in clinical trials. In particular, the application of immune checkpoint inhibitors, which have received increasing attention in the field of cancer treatment, is a possible research path. Interestingly, these two therapies generally complement each other at some stages of HCC, bringing new hope for patients with advanced HCC. In this paper, we discuss the research progress of targeted therapy and immunotherapy for HCC in recent years, which will provide a reference for the further development of drugs for HCC.

Discovery of Selective, Covalent FGFR4 Inhibitors with Antitumor Activity in Models of Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) accounts for a majority of primary liver cancer and is one of the most common forms of cancer worldwide. Aberrant signaling of the FGF19-FGFR4 pathway leads to HCC in mice and is hypothesized to be a driver in FGF19 amplified HCC in humans. Multiple small molecule inhibitors have been pursued as targeted therapies for HCC in recent years, including several selective FGFR4 inhibitors that are currently being evaluated in clinical trials. Herein, we report a novel series of highly selective, covalent 2-amino-6,8-dimethyl-pyrido[2,3-d]pyrimidin-7(8H)-ones that potently and selectively inhibit FGFR4 signaling through covalent modification of Cys552, which was confirmed by X-ray crystallography. Correlative target occupancy and pFGFR4 inhibition were observed in vivo, as well as tumor regression in preclinical models of orthotopic and sorafenib-resistant HCC.

Cancer Stem Cells: A Potential Breakthrough in HCC-Targeted Therapy

Cancer stem cells (CSCs) are subpopulations of cells with stem cell characteristics that produce both cancerous and non-tumorigenic cells in tumor tissues. The literature reports that CSCs are closely related to the development of hepatocellular carcinoma (HCC) and promote the malignant features of HCC such as high invasion, drug resistance, easy recurrence, easy metastasis, and poor prognosis. This review discusses the origin, molecular, and biological features, functions, and applications of CSCs in HCC in recent years; the goal is to clarify the importance of CSCs in treatment and explore their potential value in HCC-targeted therapy.

Non-alcoholic Fatty Liver Disease: Growing Burden, Adverse Outcomes and Associations.

Nonalcoholic fatty liver disease (NAFLD) is a systemic disorder with a complex multifactorial pathogenesis and heterogenous clinical manifestations. NAFLD, once believed to be an innocuous condition, has now become the most common cause of chronic liver disease in many countries worldwide. NAFLD is already highly prevalent in the general population, and owing to a rising incidence of obesity and diabetes mellitus, the incidence of NAFLD and its impact on global healthcare are expected to increase in the future. A subset of patients with NAFLD develops progressive liver disease leading to cirrhosis, hepatocellular carcinoma, and liver failure. NAFLD has emerged as one of the leading causes of cirrhosis and hepatocellular carcinoma in recent years. Moreover, HCC can occur in NAFLD even in absence of cirrhosis. Compared with the general population, NAFLD increases the risk of liver-related, cardiovascular and all-cause mortality. NAFLD is bidirectionally associated with metabolic syndrome. NAFLD increases the risk and contributes to aggravation of the pathophysiology of atherosclerosis, cardiovascular diseases, diabetes mellitus, and chronic kidney disease. In addition, NAFLD is linked to colorectal polyps, polycystic ovarian syndrome, osteoporosis, obstructive sleep apnea, stroke, and various extrahepatic malignancies. Extended resection of steatotic liver is associated with increased risk of liver failure and mortality. There is an increasing trend of NAFLD-related cirrhosis requiring liver transplantation, and the recurrence of NAFLD in such patients is almost universal. This review discusses the growing burden of NAFLD, its outcomes, and adverse associations with various diseases.

Research progress of reactive oxygen species and hepatocellular carcinoma

Metabolism is a necessary condition for cell survival and development. Reactive oxygen species arise from cell metabolism, while maintaining normal physiological activity of cells, reactive oxygen species can also cause normal cells to transform into tumor cells. Compared with normal cells, hepatocellular carcinoma cells produce and accumulate more reactive oxygen species during the metabolic process due to metabolic changes. These accumulated reactive oxygen species not only can promote the occurrence and development of hepatocellular carcinoma, but also can endanger the survival of it. This article summarizes the research of reactive oxygen species and hepatocellular carcinoma in recent years. Key words: Reactive oxygen species; Hepatocellular carcinoma; Mitochondria