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1.
Long noncoding RNA FEZF1-AS1 in human cancers.
Zhou, Y, Xu, S, Xia, H, Gao, Z, Huang, R, Tang, E, Jiang, X
Clinica chimica acta; international journal of clinical chemistry. 2019;:20-26
Abstract
Long noncoding RNAs (lncRNAs) have been shown to play key roles in various human tumors. Ectopic expression of the lncRNA FEZ finger zinc 1 antisense 1 (FEZF1-AS1) have been reported in different cancers, including colorectal cancer, gastric neoplasia, hepatocellular carcinoma and so on. Summarizing all literature correlated with FEZF1-AS1, it is obvious that FEZF1-AS1 is mainly involved in tumorigenesis and progression through competing endogenous RNA (ceRNA) which sponges tumor-suppressive microRNA (miRNA) and recruiting mechanism. Moreover, the aberrant expression of FEZF1-AS1 is related to clinical features of patients with cancers, and regulates cellular proliferation, anti-apoptosis, invasion and metastasis through diverse underlying mechanisms. The role of FEZF1-AS1 in carcinogenesis and progression suggests that it may be a potential diagnostic biomarker or a novel therapeutic target for cancers.
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2.
Lenvatinib: A Review in Hepatocellular Carcinoma.
Al-Salama, ZT, Syed, YY, Scott, LJ
Drugs. 2019;(6):665-674
Abstract
Lenvatinib (Lenvima®) is an oral small molecule inhibitor of multiple receptor tyrosine kinases, and is approved for the first-line treatment of patients with unresectable hepatocellular carcinoma (HCC) in the USA, EU, Japan and China. The approval of lenvatinib was based on results of the randomized, open-label, multinational, non-inferiority phase III REFLECT trial in patients with unresectable HCC, who had not received treatment for advanced disease. In REFLECT, lenvatinib was non-inferior, but not superior, to sorafenib (current standard of care) for overall survival (OS). However, lenvatinib was associated with significant improvements compared with sorafenib in terms of all secondary endpoints [higher objective response rate (ORR), and longer progression-free survival (PFS) and time to progression (TTP)]. Lenvatinib had a generally manageable tolerability profile in REFLECT, with the most common treatment-emergent adverse events being hypertension, diarrhoea, decreased appetite and decreased weight. Given its non-inferior efficacy to sorafenib and manageable tolerability profile, lenvatinib represents a long-awaited alternative option to sorafenib for the first-line systemic treatment of patients with unresectable HCC. Further clinical experience may be required to fully define the position of lenvatinib in this setting.
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3.
Prevention of Hepatocellular Carcinoma by Statins: Clinical Evidence and Plausible Mechanisms.
Kim, G, Kang, ES
Seminars in liver disease. 2019;(2):141-152
Abstract
Statins, or 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, are widely used to treat hypercholesterolemia for primary and secondary prevention of cardiovascular disease. Statins inhibit HMG-CoA reductase, the rate-limiting step in cholesterol synthesis, and modulate the downstream signaling of the mevalonate pathway. In addition to the primary effect, the antitumor effect of statins can be associated with mevalonate pathway-mediated and nonmevalonate pathway-mediated mechanisms, which improve endothelial function and lead to proapoptotic, antiproliferative, antiinflammatory, and antifibrotic properties. Statins are implicated in the improvement of metabolic status. Statins are orally available and safely and widely used for long-term treatment; they represent a novel approach for the prevention and treatment for hepatocellular carcinoma (HCC). Although several observational studies and experimental studies have revealed the preventive and therapeutic potential of statins for HCC treatment, further prospective interventional studies and randomized control trials are warranted to confirm these observations.
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4.
90Y-Loaded Microsphere SIRT of HCC Patients With Portal Vein Thrombosis: High Clinical Impact of 99mTc-MAA SPECT/CT-Based Dosimetry.
Garin, E, Rolland, Y, Edeline, J
Seminars in nuclear medicine. 2019;(3):218-226
Abstract
Radioembolization with 90Y-loaded microspheres based on classical prescription methods is increasingly applied to hepatocellular carcinoma (HCC) patients with portal vein thrombosis (PVT). In recent years, pretherapeutic predictive dosimetry based on technetium-99m macroaggregated albumin (MAA) quantitative scintigraphy using SPECT/CT has been developed. This paper presents an overview on the MAA-based dosimetry concept, discusses important confounding factors, such segmentation methods, and specific angiographic considerations required for a simulation-based dosimetric evaluation. The concept of "dosimetric angiography" is then introduced for the first time. Main results available are reported as a threshold tumor dose, allowing a response, between 100 and 120 Gy with 90Y-loaded resin microspheres and between 205 and 257 Gy with 90Y-loaded glass microspheres. Impact of MAA-based dosimetry and MAA PVT targeting on overall survival is also reported. Due to those dosimetric advances, personalized dosimetric approaches based on MAA dosimetry are now available, with specific endpoints, for both 90Y-loaded resin or glass microsphere. The clinical impact of personalized dosimetry in PVT patients is particularly high, as a median overall survival of 20.2 months has been reported for good PVT candidate treated with glass microspheres (tumor-absorbed dose ≥205 Gy and good PVT targeting) as against only 3 months for poor candidate (tumor-absorbed dose <205 Gy or poor PVT targeting), and as a significant amount of patients where downstaged and resected (12%) in the same study.
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5.
Evidence Supporting LI-RADS Major Features for CT- and MR Imaging-based Diagnosis of Hepatocellular Carcinoma: A Systematic Review.
Tang, A, Bashir, MR, Corwin, MT, Cruite, I, Dietrich, CF, Do, RKG, Ehman, EC, Fowler, KJ, Hussain, HK, Jha, RC, et al
Radiology. 2018;(1):29-48
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Abstract
The Liver Imaging Reporting and Data System (LI-RADS) standardizes the interpretation, reporting, and data collection for imaging examinations in patients at risk for hepatocellular carcinoma (HCC). It assigns category codes reflecting relative probability of HCC to imaging-detected liver observations based on major and ancillary imaging features. LI-RADS also includes imaging features suggesting malignancy other than HCC. Supported and endorsed by the American College of Radiology (ACR), the system has been developed by a committee of radiologists, hepatologists, pathologists, surgeons, lexicon experts, and ACR staff, with input from the American Association for the Study of Liver Diseases and the Organ Procurement Transplantation Network/United Network for Organ Sharing. Development of LI-RADS has been based on literature review, expert opinion, rounds of testing and iteration, and feedback from users. This article summarizes and assesses the quality of evidence supporting each LI-RADS major feature for diagnosis of HCC, as well as of the LI-RADS imaging features suggesting malignancy other than HCC. Based on the evidence, recommendations are provided for or against their continued inclusion in LI-RADS. © RSNA, 2017 Online supplemental material is available for this article.
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6.
Regorafenib: A Review in Hepatocellular Carcinoma.
Heo, YA, Syed, YY
Drugs. 2018;(9):951-958
Abstract
Regorafenib (Stivarga®), a small molecule inhibitor of multiple kinases, is the first drug to be approved for the treatment of hepatocellular carcinoma (HCC) in patients who have progressed during or after sorafenib therapy. Its approval was based on the results of the randomized, double-blind, placebo-controlled, multinational, phase III RESORCE trial in patients with HCC who had progressed during sorafenib therapy. In RESORCE, regorafenib significantly prolonged overall survival (OS; primary endpoint), progression-free survival (PFS) and time to progression (TTP) compared with placebo, with the OS benefit appearing to be largely due to disease stabilization. Regorafenib had an acceptable tolerability profile. The most common treatment-related adverse events in the regorafenib group included hand-foot skin reaction, fatigue, diarrhoea and hypertension. No fatal hepatic failure was reported with regorafenib in patients with HCC in RESORCE. In conclusion, current evidence suggests that regorafenib is an important new targeted therapy option for the treatment of HCC patients who have progressed on sorafenib therapy.
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7.
Hepatocarcinoma: genetic and epigenetic features.
Lombardi, A, Grimaldi, A, Zappavigna, S, Misso, G, Caraglia, M
Minerva gastroenterologica e dietologica. 2018;(1):14-27
Abstract
HCC is the third leading cause of cancer-related deaths worldwide, accounting for about 1 million deaths annually. The incidence of HCC is highest in Asia and Africa, where the endemic high prevalence of hepatitis B and hepatitis C strongly predisposes to the development of chronic liver disease and subsequent development of HCC. Patients with HCC generally present at an advanced stage due to compensated cirrhosis defined by the absence of pathognomonic symptoms, resulting in death within 6 to 20 months, suggesting an urgent need in treatment modalities that will dramatically decrease the mortality rate of HCC. The molecular hepatocarcinogenesis is, however, a gradual process during which genetic alterations progressively accumulate and lead to HCC through intermediate preneoplastic stages. With the advent of whole genome sequencing tools, various mutations associated with HCC have been identified, which have advanced our molecular understanding of HCC. However, the frequency of these mutations is rare, and these genetic mutations only partly explain the etiology of the disease. Better understanding and characterization of novel genetic and epigenetic alterations, which are important to hepatocarcinogenesis, may help understand the molecular pathogenesis of HCC, as well as providing novel therapeutic targets for HCC treatment. Further consideration should be given to developing more effective molecular diagnostic markers and targeted drug therapy.
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8.
Hand-foot skin reaction is a beneficial indicator of sorafenib therapy for patients with hepatocellular carcinoma: a systemic review and meta-analysis.
Wang, P, Tan, G, Zhu, M, Li, W, Zhai, B, Sun, X
Expert review of gastroenterology & hepatology. 2018;(1):1-8
Abstract
BACKGROUND Sorafenib remains the only standard first-line drug for advanced hepatocellular carcinoma (HCC). Hand-foot skin reaction (HFSR) is a very common side-effect in patients treated with sorafenib, and also affects the treatment schedule and quality of life. However, the association of HFSR and response of HCC to sorafenib remain unclear. METHODS Databases including PubMed, EMBASE, Web of Science and Cochrane Central Register of Controlled Trials were searched up to May 7th, 2017. Review Manager 5.3 software was adopted for performing meta-analyses, Newcastle-Ottawa Scale for assessing the bias of cohort studies, and GRADEprofler software for further assessing outcomes obtained from meta-analyses. RESULTS 1478 articles were reviewed, and 12 cohort studies with 1017 participants were included in the analyses. The pooled hazard ratio (HR) of overall survival is 0.45 (95% confidence interval (CI) 0.36, 0.55; P < 0.00001; I2 = 35%). The pooled HR of time to progression is 0.41 (95% CI 0.28, 0.60; P < 0.00001; I2 = 0%). Patients suffering HFSR had significantly better outcomes from sorafenib therapy than those without HFSR. CONCLUSIONS The results indicate that HFSR is a beneficial indicator for HCC patients receiving sorafenib therapy. However, molecular mechanisms accounting for sorafenib-induced HFSR in HCC patients remain.
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9.
Regorafenib for the treatment of hepatocellular carcinoma.
Tovoli, F, Granito, A, De Lorenzo, S, Bolondi, L
Drugs of today (Barcelona, Spain : 1998). 2018;(1):5-13
Abstract
Hepatocellular carcinoma (HCC) is a worldwide problem, with a high prevalence in nonindustrialized countries and a rising incidence in industrialized countries as well. Its close association with chronic liver diseases and liver cirrhosis represents a significant challenge in its treatment. A front-line systemic treatment for unresectable cases of HCC (sorafenib) was identified only in 2007. Following a decade of failed clinical trials with a wide range of drugs for second-line treatment, regorafenib proved its efficacy as a second-line treatment in 2016, when the randomized, placebo-controlled, phase III RESORCE trial demonstrated a meaningful increase in overall survival in the regorafenib treatment arm compared with the placebo arm (10.6 vs. 7.8 months). In this monograph we review the main preclinical and clinical findings in the trials assessing regorafenib for the treatment of HCC patients.
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10.
[Systemic treatment options of primary hepatocellular carcinoma].
Dank, M, Padányi, P
Magyar onkologia. 2018;(1):53-61
Abstract
Hepatocellular carcinoma is the most common primary malignancy of the liver, with increasing incidence worldwide. Chronic liver diseases, especially liver cirrhosis, are the primary risk factors in the pathogenesis. Curative therapy is usually possible only in early disease, however, most cases are diagnosed at advanced stage. Until recently sorafenib was the only viable option for systemic treatment, however, over the past years many new targeted and immunotherapy drugs proved to be efficient in first and second line as well.