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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 -
The Surgical Clinics of North America Feb 2024Liver transplantation is the only curative treatment of many patients with HCC. To be successful, patients must undergo careful multidisciplinary evaluation and... (Review)
Review
Liver transplantation is the only curative treatment of many patients with HCC. To be successful, patients must undergo careful multidisciplinary evaluation and neoadjuvant treatment for bridging or downstaging. Patients with stable disease for 6 months are listed for transplant, after which regular surveillance is required to detect recurrence.
Topics: Humans; Carcinoma, Hepatocellular; Liver Neoplasms; Neoplasm Staging; Neoplasm Recurrence, Local; Liver Transplantation; Treatment Outcome
PubMed: 37953029
DOI: 10.1016/j.suc.2023.09.002 -
Hepatology Communications Apr 2024
Topics: Humans; Liver Neoplasms
PubMed: 38466874
DOI: 10.1097/HC9.0000000000000398 -
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 -
Current Opinion in Organ Transplantation Feb 2024The success of liver transplantation (LT) in treating unresectable hepatocellular carcinoma (HCC) has resulted in interest in LT for other oncologic conditions. Here, we... (Review)
Review
PURPOSE OF REVIEW
The success of liver transplantation (LT) in treating unresectable hepatocellular carcinoma (HCC) has resulted in interest in LT for other oncologic conditions. Here, we discuss the role of LT for rare oncologic indications including metastatic gastroenteropancreatic neuroendocrine tumors (GEP-NETs), hepatic epitheliod hemangioendothelioma (HEHE), fibrolamellar hepatocellular carcinoma (FLC), and hepatic angiosarcoma (HAS).
RECENT FINDINGS
Conditions reviewed have been documented indications for LT in the available literature. We summarize the experience of LT for these indications and proposed management guidelines.
SUMMARY
GEP-NETs with isolated metastases to the liver can be treated with LT with excellent long-term outcomes (10-year survival 88%) if strict selection criteria are used (low-intermediate grade, Ki-67% < 20%, complete resection of primary tumor, stable disease for 6 months, <50% hepatic involvement). HEHE is a rare hepatic tumor for which LT can be performed with reported 10-year survival around 70%. FLC is a distinct clinical entity to HCC and is optimally treated with surgical resection though experience with LT is described in observational series (5-year survival 50%, recurrence in 10%). HAS is a rapidly progressive tumor with a dismal prognosis with or without treatment, including LT.
Topics: Humans; Carcinoma, Hepatocellular; Liver Neoplasms; Liver Transplantation; Treatment Outcome; Neoplasm Recurrence, Local
PubMed: 37851086
DOI: 10.1097/MOT.0000000000001118 -
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 -
The British Journal of Radiology Nov 2023Microvascular invasion (MVI) is an independent risk factor for the early recurrence and poor survival of hepatocellular carcinoma (HCC). This study aims to investigate...
OBJECTIVE
Microvascular invasion (MVI) is an independent risk factor for the early recurrence and poor survival of hepatocellular carcinoma (HCC). This study aims to investigate the potential clinical value of dynamic contrast-enhanced ultrasound (DCE-ultrasound)-Sonazoid in pre-operatively assessing MVI in HCC.
METHODS AND MATERIALS
This single centre prospective study included 140 patients with histopathologically confirmed single HCC lesions. Patients were classified according to the post-operative pathological information presence of MVI: MVI+ group ( = 32) and MVI- group ( = 108). All patients underwent DCE-ultrasound within 1 week before surgery. The quantitative perfusion parameters of HCC lesions, margins of HCC lesions, and distal liver parenchyma were obtained and analyzed.
RESULTS
Clinicopathological (serum alpha-fetoprotein, Des-gamma-carboxyprothrombin, and pathological grade) and grayscale imaging features (tumor size) were significantly different between the MVI+ and MVI- groups ( < 0.05). Further quantitative analysis showed that when comparing the MVI+ and MVI- groups, half-decrease time and wash-out rate of HCC lesions and peak enhancement in the arterial phase of difference between the margin area of HCC and distal liver parenchyma were significantly different ( = 0.045, = 0.035, and = 0.023, respectively). Combining the above three quantitative parameters, the accuracy, sensitivity, specificity, positive-predictive value, and negative-predictive value were 69.3% (97/140), 37.8% (17/45), 84.3% (80/95), 53.1% (17/32), 74.1% (80/108), respectively.
CONCLUSION
DCE-ultrasound with quantitative perfusion analysis has the potential to predict MVI in HCC lesions.
ADVANCES IN KNOWLEDGE
DCE-ultrasound with quantitative perfusion analysis has the potential to predict MVI in HCC lesions.
Topics: Humans; Carcinoma, Hepatocellular; Liver Neoplasms; Prospective Studies; Retrospective Studies; Neoplasm Invasiveness; Ultrasonography
PubMed: 37750942
DOI: 10.1259/bjr.20230164 -
Best Practice & Research. Clinical... Sep 2023Neuroendocrine neoplasms represent an uncommon disease with an increasing incidence. Thanks to improvements in diagnostic and therapeutic methods, metastases previously... (Review)
Review
Neuroendocrine neoplasms represent an uncommon disease with an increasing incidence. Thanks to improvements in diagnostic and therapeutic methods, metastases previously considered uncommon, such as bone metastases, or even very rare, such as brain, orbital and cardiac metastases, are more frequently found in daily practice. Due to the great heterogeneity of these neoplasms, there is a lack of high-quality evidence on the management of patients with these types of metastases. The aim of this review is to provide the current state of the art, reviewing neuroendocrine neoplasm specific studies and useful information from other tumor types and to propose a treatment recommendation with algorithms to consider in daily clinical practice.
Topics: Humans; Neuroendocrine Tumors; Melanoma; Skin Neoplasms; Liver Neoplasms
PubMed: 37270333
DOI: 10.1016/j.beem.2023.101784 -
Current Treatment Options in Oncology Dec 2023The treatment of neuroendocrine neoplasm (NEN) liver metastases involves a multidisciplinary approach that includes liver-directed therapies (LDT) and systemic... (Review)
Review
The treatment of neuroendocrine neoplasm (NEN) liver metastases involves a multidisciplinary approach that includes liver-directed therapies (LDT) and systemic treatments, such as peptide receptor radionuclide therapy (PRRT). LDT has demonstrated efficacy in rapidly reducing tumor bulk, improving symptoms, and delaying disease progression. Interventional radiologists should be consulted prior to switching therapy for patients with progressive or symptomatic neuroendocrine tumor liver metastases. Long-term follow-up data on the safety of Yttrium-90 radioembolization before and after PRRT remain limited. Therefore, a more conservative approach may be to preferentially employ transarterial embolization (TAE) or transarterial chemoembolization (TACE) for patients' somatostatin receptor-avid disease who may be future candidates for PRRT. Notable exceptions where radioembolization may be a preferred treatment strategy may be patients with history of biliary tract instrumentation, asymmetric unilobar disease distribution, and rapidly progressive diffuse liver involvement. Selection of local treatment modality, sequencing, and combination of LDT with systemic therapy require further investigation.
Topics: Humans; Neuroendocrine Tumors; Chemoembolization, Therapeutic; Liver Neoplasms; Carcinoma, Hepatocellular; Receptors, Peptide; Radioisotopes; Treatment Outcome
PubMed: 38100020
DOI: 10.1007/s11864-023-01152-6