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Cell Death & Disease Aug 2023With technological advancements, radiotherapy (RT) has become an effective non-surgical treatment for hepatocellular carcinoma (HCC), comprehensively improving the local...
With technological advancements, radiotherapy (RT) has become an effective non-surgical treatment for hepatocellular carcinoma (HCC), comprehensively improving the local control rate of patients with HCC. However, some patients with HCC still experience radio-resistance, cancer recurrence, and distant metastasis following RT. Our previous study has revealed that hexokinase 2 (HK2), a potent oncogene, was overexpressed in radio-resistant HCC cell lines; however, its role in HCC radio-resistance remains elusive. Here, we confirmed the upregulation of HK2 in HCC tissue, which is related to unfavorable prognosis in patients with HCC, and demonstrated that HK2 exerts a radio-resistant role by attenuating apoptosis and promoting proliferation in HCC cell lines. HK2 downregulation combined with ionizing radiation showed an excellent synergistic lethal effect. Mechanistically, HK2 alleviated ionizing radiation-mediated apoptosis by complexing with pro-apoptotic protein aminoacyl tRNA synthetase complex interacting multifunctional protein 2 (AIMP2) while enhancing its autophagic lysosomal-dependent degradation, thereby increasing radio-resistance of HCC. Pharmacologically, ketoconazole, an FDA-approved antifungal drug, served as an inhibitor of HK2 and synergistically enhanced the efficacy of RT. Our results indicated that HK2 played a vital role in radio-resistance and could be a potential therapeutic target for improving RT efficacy in HCC.
Topics: Humans; Autophagy; Carcinoma, Hepatocellular; Cell Line, Tumor; Cell Proliferation; Hexokinase; Liver Neoplasms; Neoplasm Recurrence, Local; Nuclear Proteins
PubMed: 37524692
DOI: 10.1038/s41419-023-06009-2 -
International Journal of Molecular... Aug 2023Hepatocellular carcinoma (HCC) accounts for 7% of all malignancies and about 90% of all primary liver malignancies, making it the most common type of malignant liver...
Hepatocellular carcinoma (HCC) accounts for 7% of all malignancies and about 90% of all primary liver malignancies, making it the most common type of malignant liver neoplasm [...].
Topics: Humans; Carcinoma, Hepatocellular; Liver Neoplasms
PubMed: 37628717
DOI: 10.3390/ijms241612536 -
Role of exosomes in the development, diagnosis, prognosis and treatment of hepatocellular carcinoma.Molecular Medicine (Cambridge, Mass.) Oct 2023Hepatocellular carcinoma (HCC) is the most common primary liver cancer. It is characterized by occult onset resulting in most patients being diagnosed at advanced stages... (Review)
Review
Hepatocellular carcinoma (HCC) is the most common primary liver cancer. It is characterized by occult onset resulting in most patients being diagnosed at advanced stages and with poor prognosis. Exosomes are nanoscale vesicles with a lipid bilayer envelope released by various cells under physiological and pathological conditions, which play an important role in the biological information transfer between cells. There is growing evidence that HCC cell-derived exosomes may contribute to the establishment of a favorable microenvironment that supports cancer cell proliferation, invasion, and metastasis. These exosomes not only provide a versatile platform for diagnosis but also serve as a vehicle for drug delivery. In this paper, we review the role of exosomes involved in the proliferation, migration, and metastasis of HCC and describe their application in HCC diagnosis and treatment. We also discuss the prospects of exosome application in HCC and the research challenges.
Topics: Humans; Carcinoma, Hepatocellular; Liver Neoplasms; Exosomes; Cell Proliferation; Tumor Microenvironment
PubMed: 37848835
DOI: 10.1186/s10020-023-00731-5 -
Hepatology Communications Apr 2024
Topics: Humans; Liver Neoplasms
PubMed: 38466874
DOI: 10.1097/HC9.0000000000000398 -
Cancer Metastasis Reviews Jun 2024Hepatocellular carcinoma (HCC) is an increasing burden on global public health and is associated with enhanced lipogenesis, fatty acid uptake, and lipid metabolic... (Review)
Review
Hepatocellular carcinoma (HCC) is an increasing burden on global public health and is associated with enhanced lipogenesis, fatty acid uptake, and lipid metabolic reprogramming. De novo lipogenesis is under the control of the transcription factor sterol regulatory element-binding protein 1 (SREBP-1) and essentially contributes to HCC progression. Here, we summarize the current knowledge on the regulation of SREBP-1 isoforms in HCC based on cellular, animal, and clinical data. Specifically, we (i) address the overarching mechanisms for regulating SREBP-1 transcription, proteolytic processing, nuclear stability, and transactivation and (ii) critically discuss their impact on HCC, taking into account (iii) insights from pharmacological approaches. Emphasis is placed on cross-talk with the phosphatidylinositol-3-kinase (PI3K)-protein kinase B (Akt)-mechanistic target of rapamycin (mTOR) axis, AMP-activated protein kinase (AMPK), protein kinase A (PKA), and other kinases that directly phosphorylate SREBP-1; transcription factors, such as liver X receptor (LXR), peroxisome proliferator-activated receptors (PPARs), proliferator-activated receptor γ co-activator 1 (PGC-1), signal transducers and activators of transcription (STATs), and Myc; epigenetic mechanisms; post-translational modifications of SREBP-1; and SREBP-1-regulatory metabolites such as oxysterols and polyunsaturated fatty acids. By carefully scrutinizing the role of SREBP-1 in HCC development, progression, metastasis, and therapy resistance, we shed light on the potential of SREBP-1-targeting strategies in HCC prevention and treatment.
Topics: Humans; Carcinoma, Hepatocellular; Liver Neoplasms; Sterol Regulatory Element Binding Protein 1; Animals; Signal Transduction; Gene Expression Regulation, Neoplastic; Molecular Targeted Therapy
PubMed: 38036934
DOI: 10.1007/s10555-023-10156-5 -
European Radiology Apr 2024Hepatocellular carcinoma (HCC) is the most common primary hepatic malignancy and a leading cause of cancer related death worldwide. Current guidelines for the... (Review)
Review
Hepatocellular carcinoma (HCC) is the most common primary hepatic malignancy and a leading cause of cancer related death worldwide. Current guidelines for the noninvasive diagnosis of HCC are provided by the European Association for the Study of the Liver (EASL), the American Association for the Study of Liver Diseases (AASLD) which endorsed the Liver Imaging Reporting and Data System (LI-RADS) algorithm, the Korean Liver Cancer Association-National Cancer Center (KLCA-NCC), and the Asian-Pacific Association for the Study of the Liver (APASL). These allow the diagnosis of HCC in high-risk patients in the presence of typical imaging features on contrast-enhanced CT, MRI, or contrast-enhanced ultrasound. Size, non-rim arterial phase hyperenhancement, non-peripheral washout, enhancing capsule, and growth are major imaging features and they should be combined for the diagnosis of HCC. This article provides concise and relevant practice recommendations aimed at general radiologist audience, summarizing the best practice and informing on the essential imaging criteria for the diagnosis of HCC, while also discussing the high-risk population criteria, imaging modalities, and imaging features according to the current guidelines. KEY POINTS: • Noninvasive diagnosis of hepatocellular carcinoma (HCC) can be provided only in patients at high risk. • Contrast-enhanced CT or MRI are the first-line imaging exams for the diagnosis of HCC. • Major imaging features should be combined to provide the diagnosis of definitive HCC.
Topics: Humans; Carcinoma, Hepatocellular; Liver Neoplasms; Tomography, X-Ray Computed; Contrast Media; Magnetic Resonance Imaging; Retrospective Studies; Sensitivity and Specificity
PubMed: 38379018
DOI: 10.1007/s00330-024-10606-w -
International Journal of Surgery... Sep 2023Despite retrospective studies comparing anatomical liver resection (AR) and non-anatomical liver resection (NAR), the efficacy and benefits of AR for hepatocellular... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Despite retrospective studies comparing anatomical liver resection (AR) and non-anatomical liver resection (NAR), the efficacy and benefits of AR for hepatocellular carcinoma remain unclear.
MATERIALS AND METHODS
The authors systemically reviewed MEDLINE, Embase, and Cochrane Library for propensity score matched cohort studies that compared AR and NAR for hepatocellular carcinoma. Primary outcomes were overall survival (OS) and recurrence-free survival (RFS). Secondary outcomes were recurrence patterns and perioperative outcomes.
RESULTS
Overall, 22 propensity score matched studies (AR, n =2,496; NAR, n =2590) were included. AR including systemic segmentectomy was superior to NAR regarding the 3-year and 5-year OS. AR showed significantly better 1-year, 3-year, and 5-year RFS than NAR, with low local and multiple intrahepatic recurrence rates. In the subgroup analyses of tumour diameter less than or equal to 5 cm and tumours with microscopic spread, the RFS in the AR group was significantly better than that in the NAR group. Patients with cirrhotic liver in the AR group showed comparable 3-year and 5-year RFS with the NAR group. Postoperative overall complications were comparable between AR and NAR.
CONCLUSIONS
This meta-analysis demonstrated that AR showed better OS and RFS with a low local and multiple intra-hepatic recurrence rate than NAR, especially in patients with tumour diameter less than or equal to 5 cm and non-cirrhotic liver.
Topics: Humans; Carcinoma, Hepatocellular; Liver Neoplasms; Retrospective Studies; Hepatectomy; Propensity Score; Postoperative Complications; Neoplasm Recurrence, Local
PubMed: 37247010
DOI: 10.1097/JS9.0000000000000503 -
Cancer Biology & Medicine Nov 2023Over the past 2 decades, cancer stem cells (CSCs) have been identified as the root cause of cancer occurrence, progression, chemoradioresistance, recurrence, and... (Review)
Review
Over the past 2 decades, cancer stem cells (CSCs) have been identified as the root cause of cancer occurrence, progression, chemoradioresistance, recurrence, and metastasis. Targeting CSCs is a novel therapeutic strategy for cancer management and treatment. Liver cancer (LC) is a malignant disease that can endanger human health. Studies are increasingly suggesting that changes in the liver mechanical microenvironment are a primary driver triggering the occurrence and development of liver cancer. In this review, we summarize current understanding of the roles of the liver mechano-microenvironment and liver cancer stem cells (LCSCs) in liver cancer progression. We also discuss the relationship between the mechanical heterogeneity of liver cancer tissues and LCSC recruitment and metastasis. Finally, we highlight potential mechanosensitive molecules in LCSCs and mechanotherapy in liver cancer. Understanding the roles and regulatory mechanisms of the mechano-microenvironment and LCSCs may provide fundamental insights into liver cancer progression and aid in further development of novel therapeutic strategies.
Topics: Humans; Liver Neoplasms; Neoplastic Stem Cells; Tumor Microenvironment
PubMed: 38009775
DOI: 10.20892/j.issn.2095-3941.2023.0229 -
Best Practice & Research. Clinical... Sep 2023Neuroendocrine tumours commonly metastasise to the liver, particularly those arising from the intestinal tract and pancreas. Whilst surgery offers the only approach with... (Review)
Review
Neuroendocrine tumours commonly metastasise to the liver, particularly those arising from the intestinal tract and pancreas. Whilst surgery offers the only approach with intent to cure, the vast majority of patients with neuroendocrine liver metastases are ineligible. Liver-directed interventional therapies seek to exploit the patho-anatomy of the blood supply of hepatic metastases to deliver therapy to liver deposits. This may involve percutaneous ablation, bland embolization, or the selective infusion of chemotherapeutics, targeted agents or radiolabelled embolic material. Retrospective case series evidence has characterised objective response rates, disease control rates, and longer-term outcomes associated with each approach. Recent advances in this field include ongoing comparative trials of different techniques, but more importantly, combinations of interventional liver-directed therapies and other systemic therapy in multimodal treatment concepts.
Topics: Humans; Neuroendocrine Tumors; Retrospective Studies; Liver Neoplasms; Antineoplastic Agents; Embolization, Therapeutic
PubMed: 37468404
DOI: 10.1016/j.beem.2023.101798 -
Journal of Cellular and Molecular... May 2024Liver diseases include all types of viral hepatitis, alcoholic liver disease (ALD), nonalcoholic fatty liver disease (NAFLD), cirrhosis, liver failure (LF) and... (Review)
Review
Liver diseases include all types of viral hepatitis, alcoholic liver disease (ALD), nonalcoholic fatty liver disease (NAFLD), cirrhosis, liver failure (LF) and hepatocellular carcinoma (HCC). Liver disease is now one of the leading causes of disease and death worldwide, which compels us to better understand the mechanisms involved in the development of liver diseases. Anoctamin 1 (ANO1), a calcium-activated chloride channel (CaCC), plays an important role in epithelial cell secretion, proliferation and migration. ANO1 plays a key role in transcriptional regulation as well as in many signalling pathways. It is involved in the genesis, development, progression and/or metastasis of several tumours and other diseases including liver diseases. This paper reviews the role and molecular mechanisms of ANO1 in the development of various liver diseases, aiming to provide a reference for further research on the role of ANO1 in liver diseases and to contribute to the improvement of therapeutic strategies for liver diseases by regulating ANO1.
Topics: Humans; Anoctamin-1; Liver Diseases; Animals; Signal Transduction; Neoplasm Proteins; Liver Neoplasms; Carcinoma, Hepatocellular; Gene Expression Regulation
PubMed: 38685684
DOI: 10.1111/jcmm.18320