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One of the most frequent malignant tumors seen in clinics is primary liver cancer, also referred to as the "king of cancers." Therefore, the necessity for an effective and precise detection technique is urgent. Compared with the cantilever beam, the double-ended clamped beam has the characteristics of higher resonance frequency and stronger noise immunity, so it has a good application prospect as a biosensor. This paper takes the double-ended clamped beam biosensor as the object and focuses on the method that can be applied to the early diagnosis and detection of liver cancer. The manufacturing process of the double-ended clamped beam and the biofunctional modification of the beam surface were introduced. Meantime, this paper introduces the integration of the composite double-ended clamped beam biosensor system. As a result, a high-sensitivity, high-reliability in situ real-time monitoring technology for early-stage liver cancer is proposed. A composite double-ended clamped beam made of silicon and silicon nitride is used. The size of the double-ended clamped beam is 280 µm × 50µm × 5µm. This paper provides a low-cost, portable, and rapid early diagnosis method for liver cancer, which has very significant application value in the field of early cancer screening. [ABSTRACT FROM AUTHOR]

Tumour development is not only an independent event of genetic mutation and overgrowth of tumour cells but is the result of a synergistic interaction between a malignant tumour and its surrounding tumour stromal microenvironment. In this paper, we address the shortcomings of current tumour therapy by focussing on the tumour itself and the surrounding microenvironment to achieve a two-pronged targeting model. In this paper, a dual-targeting, pH/reactive oxygen species (ROS) sensitive nano-drug delivery system for tumour cells and CAFs was designed. A hyaluronic acid (HA) with CD44 receptor targeting on the surface of tumour cells was selected as the main carrier material, and a dipeptide Z-glycine-proline (ZGP) with specific targeting of fibroblast activating protein (FAP) on the surface of CAFs was modified on HA to achieve precise targeting of CAFs, open the physical barrier of tumour cells and improve the deep penetration effect of the tumour, while introducing thioketone bond and ketone condensation bond to take advantage of the highly reactive ROS and low pH microenvironment at the tumour site to achieve chemical bond breaking of nano micelles encapsulating paclitaxel (PTX), drug release, and thus drug aggregation at the tumour site and improved bioavailability of the drug. [ABSTRACT FROM AUTHOR]

Since 1986, the first microcantilever applied in atomic force microscope, the device manufacturing technology, driving method and readout technology have improved significantly. In this paper, five readout technologies will be introduced in detail, and they are optical readout, piezoelectric readout, piezoresistive readout, capacitance readout and electron tunneling readout, respectively. Among them, the piezoresistive readout technology attracts a large number of researchers due to simple detection equipment, easy integration, and lower cost. In order to improve the detection accuracy of the piezoresistive microcantilever, a detection system based on FPGA is proposed in this paper. Output signal of the piezoresistive microcantilever array sensor for alpha-fetoprote (AFP) detection was researched. The detection accuracy of 0.05 Hz is achieved, the system stability is within 0.6 Hz, and it has a precise detection level for AFP with concentration of 50 pg/ml, which makes microcantilever has potential in early diagnosis and detection of liver cancer. [ABSTRACT FROM AUTHOR]

Static robust optimization has played an important role in radiotherapy, where the decisions aim to safeguard against all possible realizations of uncertainty. However, it may lead to overly conservative decisions or too expensive treatment plans, such as delivering significantly more dose than necessary. Motivated by the success of adjustable robust optimization in reducing highly conservative decision-making of static robust optimization in applications, in this paper, we present an affinely adjustable robust optimization (AARO) model for hypoxia-based radiation treatment planning in the face of evolving data uncertainty. We establish an exact semi-definite program reformulation of the model under a so-called affine decision rule and evaluate our model and approach on a liver cancer case as a proof-of-concept. Our AARO model incorporates uncertainties both in dose influence matrix and re-oxygenation data as well as inexactness of the revealed (re-oxygenation) data. Our numerical experiments demonstrate that the adjustable model successfully handles uncertainty in both re-oxygenation and the dose matrix. They also show that, by utilizing information halfway through the treatment plan, the adjustable solutions of the AARO model outperform a static method while maintaining a similar total dose. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) is a subtype of primary liver cancer and a major cause of death. Although miRNA plays an important role in hepatocellular carcinoma, the specific regulatory network remains unclear. Therefore, this paper comprehensively describes the miRNA-related signaling pathways in HCC and the possible interactions among different signaling pathways. The aim is to lay the foundation for the discovery of new molecular targets and multi-target therapy. Based on miRNA, HCC, and signaling pathways, the literature was searched on Web of Science and PubMed. Then, common targets between different signaling pathways were found from KEGG database, and possible cross-regulation mechanisms were further studied. In this review, we elaborated from two aspects, respectively, laying a foundation for studying the regulatory mechanism and potential targets of miRNA in HCC. Non-coding RNAs have become notable molecules in cancer research in recent years, and many types of targeted drugs have emerged. From the outset, molecular targets and signal pathways are interlinked, which suggests that signal pathways and regulatory networks should be concerned in basic research, which also provides a strong direction for future mechanism research. [ABSTRACT FROM AUTHOR]

This paper deals with the design of an image enhancement algorithm which is capable of improving the quality of computed tomography (CT) images for liver cancer diagnosis. A novel soft computing technique namely fuzzy blend scheme (FBS) is proposed in this work. The FBS works in two stages. The first stage is the pre-processing stage in which the image is de-noised and sharpened by the application of a non-linear filter. In the second stage, the pre-processed output is blended with a novel fuzzy transformation function to give the contrast-enhanced image. The method is tested on 181 CT images from 15 patients of liver cancer named hepatocellular carcinoma. Quality metrics computed for the comparison of FBS with the existing methods include signal to noise ratio = 11.4270, enhancement measure = 12.30, structural similarity index = 91% and discrete entropy which is less than original image. The maximum computation time for FBS is 3.488 s. The proposed method can aid the radiologists and physicians in disease diagnosis. It will help in reducing the burden of ionic contrast reagents induced in patients for tumour visualisation. [ABSTRACT FROM AUTHOR]

Background: ABO blood type is an invariant factor. There is a link between ABO blood type and some malignancies, such as gastric, pancreatic, and skin cancer. The role of ABO blood type in the pathogenesis of hepatocellular carcinoma (HCC) remains controversial. We performed a meta-analysis to explore the relationship between ABO blood type and risk of HCC. Methods: Literature search was conducted among the PubMed, EMBASE, and Cochrane Library databases. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. Results: Seven papers were included. They included 92,847 healthy subjects, 5,463 patients with hepatitis, 294 cirrhotic patients, and 3,322 HCC patients. The proportion of blood type O was significantly lower in HCC patients than healthy subjects (OR = 0.76, 95%CI = 0.66-0.87, P < 0.0001) without any significant heterogeneity (P = 0.55, I2 = 0%). The proportions of blood types A, B, and AB were not significantly different between HCC patients and healthy subjects. The proportion of ABO blood type was not significantly different between patients with HCC and those with hepatitis or cirrhosis. Conclusion: HCC patients might have a lower proportion of blood type O than healthy subjects. Among the patients with chronic liver diseases, ABO blood type might not be associated with the risk of HCC. [ABSTRACT FROM AUTHOR]

Insulin resistance promotes the occurrence of liver cancer and decreases its chemosensitivity. Rosiglitazone (ROSI), a thiazolidinedione insulin sensitiser, could be used for diabetes with insulin resistance and has been reported to show anticancer effects on human malignant cells. In this paper, we investigated the combination of ROSI and chemotherapeutics on the growth and metastasis of insulin-resistant hepatoma. In vitro assay, ROSI significantly enhanced the inhibitory effects of adriamycin (ADR) on the proliferation, autophagy and migration of insulin-resistant hepatoma HepG2/IR cells via downregulation of EGFR/ERK and AKT/mTOR signalling pathway. In addition, ROSI promoted the apoptosis of HepG2/IR cells induced by ADR. In vivo assay, high fat and glucose diet and streptozotocin (STZ) induced insulin resistance in mice by increasing the body weight, fasting blood glucose (FBG) level, oral glucose tolerance, fasting insulin level and insulin resistance index. Both the growth of mouse liver cancer hepatoma H22 cells and serum FBG level in insulin resistant mice were significantly inhibited by combination of ROSI and ADR. Thus, ROSI and ADR in combination showed a stronger anti-tumour effect in insulin resistant hepatoma cells accompanying with glucose reduction and might represent an effective therapeutic strategy for liver cancer accompanied with insulin resistant diabetes. [ABSTRACT FROM AUTHOR]

The exact boundary extraction of liver using abdominal computed tomography (CT) images continues to be the greatest challenge in the computer-assisted diagnosis of liver tumour, as the organ boundary is very weak. In this paper, an efficient algorithm is proposed to enhance the edge information of the CT images prior to segmentation, by means of multislice image fusion and anisotropic diffusion filtering in non-subsampled contourlet (NSCT) domain. The two adjacent slices of CT images are decomposed using NSCT, and the fusion of low- and high-frequency coefficients is obtained by means of phase congruency and sum-modified Laplacian operators, respectively. The major highlight of this work is that, prior to high-frequency fusion; the high-frequency coefficients of both images are processed using anisotropic diffusion to strengthen the edge information. Finally, the edge-enhanced image is obtained by NSCT reconstruction. The performance metrics show that the information pertaining to the edges is found to be precise in the fused image. The proposed logic, when applied to the real-time contrast-enhanced triple-phase CT image, has proven to be highly effective. All the image samples used in this work for test purpose were obtained from Jawaharlal Institute of Postgraduate Medical Education Research (JIPMER), a Medical Research Institute and Hospital at Puducherry, India. [ABSTRACT FROM AUTHOR]

In reliability or survival analysis, the hazard function plays a significant part for it can display the instantaneous failure rate at any time point. In practice, the abrupt change in hazard function at an unknown time point may occur after a maintenance activity or major operation. Under these circumstances, identifying the change point and estimating the size of the change are meaningful. In this paper, we assume that the hazard function is piecewise constant with a single jump at an unknown time. We propose the single change-point model for interval-censored survival data with a cure fraction. Estimation methods for the proposed model are investigated, and large-sample properties of the estimators are established. Simulation studies are carried out to evaluate the performance of the estimating method. The liver cancer data and breast cancer data are analyzed as the applications. [ABSTRACT FROM AUTHOR]

Tumor microenvironment is closely related to the occurrence and development of liver cancer. Tumor-associated macrophages (TAMs) are an important part of tumor microenvironment promoting tumor deterioration and metastasis by inhibiting immune cells. Previous studies showed that PI3Kγ inhibitor could reverse the phenotype of TAMs, relieve immunosuppression and sensitize chemotherapy drugs, suggesting that the combination of PI3Kγ inhibitor and chemotherapeutics is likely to bring new breakthroughs in the treatment of liver cancer. Based on it, this paper builds HES-TG100-115-CDM-PEG micelles with tumor microenvironment responsiveness that simultaneously loaded sorafenib and TG100-115 to synergistically treat liver cancer. Pharmacokinetic study showed that the prepared micelles had longer half-life than that of the free drug solutions, which was favorable for high propensity of extravasation through tumor vascular fenestrations. Under low pH and high α-amylasereductive conditions, micelles could depolymerize quickly due to the sensitivity of bonds and enhance significantly cytotoxic activity against Hep-3B liver cancer cell. Additionally, micelles demonstrated higher levels of antitumor efficiency and better tolerance against nude mouse with Hep-3B cell than the free drug solutions. These findings reveal that HES-TG100-115-CDM-PEG micelles are a promising drug delivery system in clinical comprehensive therapy of liver cancer. [ABSTRACT FROM AUTHOR]

Interoperable ontologies already exist in the biomedical field, enabling scientists to communicate with minimum ambiguity. Unfortunately, ontology languages, in the semantic web, such as OWL and RDF(S), are based on crisp logic and thus they cannot handle uncertain knowledge about an application field, which is unsuitable for the medical domain. In this paper, we focus on modeling incomplete knowledge in the classical OWL ontologies, using Bayesian networks, all keeping the semantic of the first ontology, and applying algorithms dedicated to learn parameters of Bayesian networks in order to generate the Bayesian networks. We use EM algorithm for learning conditional probability tables of different nodes of Bayesian network automatically, contrary to different tools of Bayesian networks where probabilities are inserted manually. To validate our work, we have applied our model on the diagnosis of liver cancer using classical ontology containing incomplete instances, in order to handle medical uncertain knowledge, for predicting a liver cancer. [ABSTRACT FROM AUTHOR]

Balloon-occluded transarterial chemoembolisation (B-TACE) is an intraarterial transcatheter treatment for liver cancer. In B-TACE, an artery-occluding microballoon catheter occludes an artery and promotes collateral circulation for drug delivery to tumours. This paper presents a methodology for analysing the haemodynamics during B-TACE, by combining zero-dimensional and three-dimensional modelling tools. As a proof of concept, we apply the methodology to a patient-specific hepatic artery geometry and analyse two catheter locations. Results show that the blood flow redistribution can be predicted in this proof-of-concept study, suggesting that this approach could potentially be used to optimise catheter location. [ABSTRACT FROM AUTHOR]

In recent years, liver cancer has caused great harm to human health. This study aims to use serum Raman spectroscopy combined with deep learning algorithms to classify liver cancer patients and control groups. For improving the robustness of models, we added equal proportions of Gaussian white noise of 5, 10, 15, 20, 25 dBW to enhance the data, and compared the results of convolutional neural networks and long short-term memory networks which show that the convolutional neural network combined with 10-fold data enhancement was better. The accuracy was 96.95%, indicating the great potential of this experimental model in liver cancer detection. [ABSTRACT FROM AUTHOR]

Background:Radiofrequency ablation (RFA) and percutaneous ethanol injection (PEI) are important treatments for patients with hepatocellular carcinoma (HCC) who are not eligible for resection and liver transplantation. Therefore, it is important to establish comparisons between RFA, PEI and the two therapies in combination. Aims:To evaluate the clinical efficacy and safety of combined RFA-PEI versus monotherapy with either RFA or PEI for HCC to provide references for clinical practice and further research. Methods:We searched all eligible studies published before September 2015 in the Cochrane Library, PubMed, Embase, Web of Science and Chinese databases, such as CBM, CNKI, VIP and WanFang and also retrieved papers from other sources. All relevant controlled trials were collected. Meta-analyses were performed using RevMan version 5.3 software (The Nordic Cochrane Centre, The Cochrane Collaboration, Copenhagen, Denmark). Results:Thirteen trials with 1621 patients were identified. Compared with PEI, RFA was associated with significant improvement in overall survival (OS) rate at 1, 2, 3 and 4 years, cancer-free survival (CFS) rate at 1, 2 and 3 years and complete tumour necrosis. RFA was associated with a significant reduction in the local recurrence rate at 1, 2 and 3 years. However, RFA was also associated with a higher total risk of complications. Compared with RFA alone, combined RFA-PEI was associated with a significant improvement in the OS rate at 1.5, 2 and 3 years and a significant reduction in the local recurrence rate. However, combined RFA-PEI was also associated with a higher risk of fever. Conclusion:The combination of RFA and PEI appears to be the optimal treatment strategy when considering combined RFA-PEI or either RFA or PEI alone. Combined RFA-PEI significantly improves OS and reduces the risk of local recurrence without increasing major complications. Further large-scale studies are needed to assess economic outcomes and quality of life. [ABSTRACT FROM AUTHOR]

Context:Hepatocellular carcinoma (HCC) is a common cancer around the world, with high mortality rate. Currently, there is no effective drug for the therapy of HCC. Ursolic acid (UA) is a natural product which exists in various medicinal herbs and fruits, exhibiting multiple biological effects such as its outstanding anticancer and hepatoprotective activity, which has drawn many pharmacists’ attention. Objective:This paper summarizes the current status of the hepatoprotective activity of UA analogues and explains the related mechanism, providing a clear direction for the development of novel anti-HCC drugs. Methods:All of the data resources were derived from PubMed. By comparing the IC50values and analyzing the structure–activity relationships, we listed compounds with good pharmacological activity from the relevant literature, and summarized their anti-HCC mechanism. Results:From the database, 58 new UA derivatives possessing wonderful anticancer and hepatoprotective effects were listed, and the relevant anti-HCC mechanism were discussed. Conclusion:UA’s anti-HCC effect is the result of combined action of many mechanisms. These 58 new UA derivatives, particularly compounds45and53, can be used as potential drugs for the treatment of liver cancer. [ABSTRACT FROM AUTHOR]

Metabolic reprogramming plays a critical role in hepatocarcinogenesis. However, the mechanisms regulating metabolic reprogramming in primary liver cancer (PLC) are unknown. Differentially expressed miRNAs between PLC and normal tissues were identified using bioinformatic analysis. RT-qPCR was used to determine miR-10b-5p and SCL38A2 expression levels. IHC, WB, and TUNEL assays were used to assess the proliferation and apoptosis of the tissues. The proliferation, migration, invasion, and apoptosis of PLC cells were determined using the CCK-8 assay, Transwell assay, and flow cytometry. The interaction between miR-10b-5p and SLC38A2 was determined using dual-luciferase reporter assay. A PLC xenograft model in BALB/c nude mice was established, and tumorigenicity and SLC38A2 expression were estimated. Finally, liquid chromatography - mass spectrometry (LC-MS) untargeted metabolomics was used to analyze the metabolic profiles of xenograft PLC tissues in nude mice. miR-10b-5p was a key molecule in the regulation of PLC. Compared with para-carcinoma tissues, miR-10b-5p expression was increased in tumor tissues. miR-10b-5p facilitated proliferation, migration, and invasion of PLC cells. Mechanistically, miR-10b-5p targeted SLC38A2 to promote PLC tumor growth. Additionally, miR-10b-5p altered the metabolic features of PLC in vivo. Overexpression of miR-10b-5p resulted in remarkably higher amounts of lumichrome, folic acid, octanoylcarnitine, and Beta-Nicotinamide adenine dinucleotide, but lower levels of 2-methylpropanal, glycyl-leucine, and 2-hydroxycaproic acid. miR-10b-5p facilitates the metabolic reprogramming of PLC by targeting SLC38A2, which ultimately boosts the proliferation, migration, and invasion of PLC cells. Therefore, miR-10b-5p and SLC38A2 are potential targets for PLC diagnosis and treatment. [ABSTRACT FROM AUTHOR]

This paper reports the development and application of a biosensor for the amperometric determination of galactose in the presence of human hepatocellular carcinoma cells with and without a hepatotoxic agent. The biosensor was fabricated by drop-coating 1.5% cellulose acetate on a 3 × 3 mm screen-printed carbon electrode followed by depositing 2 U of galactose oxidase. The electrodes dimensions were reduced to 3 × 0.5 mm before measurements. Hepatocellular carcinoma cells were utilized for in vitro toxicity testing by evaluating the effect of paracetamol on galactose uptake. The amperometric responses to galactose indicated that the inhibition of uptake was directly proportional to the concentration of paracetamol following 24 h of exposure to the hepatocellular carcinoma cells. These results demonstrate that the fabricated biosensor may be used for the real-time monitoring of cell metabolism and toxicity. [ABSTRACT FROM PUBLISHER]

Objective: The aim of this paper is to quantitatively investigate the thermal effects generated by the pre-focal interactions of a HIFU beam with a rib cage, in the context of minimally invasive transcostal therapy of liver malignancies. Materials and methods: HIFU sonications were produced by a phased-array MR-compatible transducer on Turkey muscle placed on a sheep thoracic cage specimen. The thoracic wall was positioned in the pre-focal zone 3.5 to 6.5 cm below the focus. Thermal monitoring was simultaneously performed using fluoroptic sensors inserted into the medullar cavity of the ribs and high resolution MR-thermometry (voxel: 1 × 1 × 5 mm3, four multi-planar slices). Results: MR-thermometry data indicated nearly isotropic distribution of the thermal energy at the ribs' surface. The temperature elevation at the focus was comparable with the pericostal temperature elevation around unprotected ribs, while being systematically inferior, by more than a factor of four on average, to the intra-medullar values. The spatial profiles of the pericostal and intra-medullar thermal build-up measurements could be smoothly connected using a Gaussian function. The dynamics of the post-sonication thermal relaxation as determined by fluoroptic measurements was demonstrated to be theoretically coherent with the experimental observations. Conclusion: The experimental findings motivate further efforts for the transfer towards clinical routine of effective rib-sparing strategies for hepatic HIFU. [ABSTRACT FROM AUTHOR]

Objectives: This paper describes the development and optimization of curcumin thermosensitive hydrogels (CTH), a kind of gel injection for intratumoral injection treatment. Methods: Aimed at increasing the content and stability of effective components, an optimal formulation of CTH was chosen based on the results from orthogonal tests and the optimal pH was determined by stability test. To investigate the hydrogels drug release in vitro, residence time by RP-HPLC and therapeutic effects on ascitic hepatocarcinoma cell strain with high metastasis potential in lymphatic system (HCA-F) solid tumors in mice. Key findings: The selected optimal formulation of CTH was: 0.2% curcumin, 20% poloxamer 407, 4% poloxamer 188, 8% polyethylene glycol 400, 12% 1,2-propanediol and pH was 6.0. The drug release determined by RP-HPLC fit to the Higuchi model. The residence time of CTH was longer than the curcumin suspensions. Intratumoral injection of the CTH can effectively inhibit the growth of HCA-F solid tumors in mice. Conclusions: The CTH prepared in this test demonstrates proper gel temperature and viscosity. It improves the solubility of curcumin with a relatively long period of drug release in vitro and residence time. Intratumoral injection of the CTH can effectively inhibit the growth of HCA-F solid tumors in mice. [ABSTRACT FROM AUTHOR]

Past failures in clinical trials have dampened the enthusiasm for studying the HGF receptor MET and postponed the development of MET-targeted drugs for cancer therapy. However, new evidence suggests that, at least in liver cancer, MET is still a promising therapeutic target, and may also be a potential target for cancer vaccines. This paper briefly highlights novel research advances in this rapidly-evolving field in the perspective of autophagy, and discusses future directions for further investigation of MET-based cancer therapy and vaccination. [ABSTRACT FROM AUTHOR]

This study was performed to determine the concentration and assess the risk of aflatoxins (AFs) i.e. aflatoxin B1 (AFB1), B2 (AFB2), G1 (AFG1), and G2 (AFG2) in wheat whole and refined flour samples for Iranian adults. Sixty-five (60.19%) out of 108 analysed samples were positive for AFB1 and total AFs (AFB1+ AFB2+ AFG1+ AFG2). The range of AFB1 and the total AFs in samples were 0.14–7.34 and 0.34–7.61 µg kg−1, respectively. While, their means were 1.70 ± 0.22 and 2.15 ± 0.23, respectively. AFB1 level in 7 (6.48%) samples exceeded maximum limits allowed according to Iran standard (5 µg kg−1) while all samples had total AFs at an acceptable level (15 µg kg−1). The incidence and concentration of AFs in wheat whole flour samples were higher than that of refined flour one. The estimated daily intake (EDI), the margin of exposure (MOE), hepatocellular cancer risk of AFB1 through flour samples were 0.004 µg kg−1 bw day−1, 108.74 and 4.12 cases per 100,000 individuals/75 years, respectively. As EDI was more than the suggested value of 0.017 ng kg−1 bw day−1 and hepatocellular cancer risk was higher than the recommended level of 0.1 cases/75 years/100,000 individuals and MOE >10,000, it could be concluded AFs level in flour samples had a health potential risk to human health. [ABSTRACT FROM AUTHOR]

In this work, a series of novel arylamide derivatives containing piperazine moiety were designed and synthesised as tubulin polymerisation inhibitors. Among 25 target compounds, compound 16f (MY-1121) exhibited low nanomolar IC50 values ranging from 0.089 to 0.238 μM against nine human cancer cells. Its inhibitory effects on liver cancer cells were particularly evident with IC50 values of 89.42 and 91.62 nM for SMMC-7721 and HuH-7 cells, respectively. Further mechanism studies demonstrated that compound 16f (MY-1121) could bind to the colchicine binding site of β-tubulin and directly act on β-tubulin, thus inhibiting tubulin polymerisation. Additionally, compound 16f (MY-1121) could inhibit colony forming ability, cause morphological changes, block cell cycle arrest at the G2 phase, induce cell apoptosis, and regulate the expression of cell cycle and cell apoptosis related proteins in liver cancer cells. Overall, the promising bioactivities of compound 16f (MY-1121) make the novel arylamide derivatives have the value for further development as tubulin polymerisation inhibitors with potent anticancer activities. [ABSTRACT FROM AUTHOR]

Background: Curcumin has been used in the treatment of several diseases; however, its low pharmacologic profile reduces its therapeutic use. Towards improving its biological activity, nanoformulations have emerged. Thus, we aimed to determine whether curcumin nanoparticles (Cur-NPs) coated with PEG/chitosan improve the treatment of liver cancer (LC) cells and underpin the molecular mechanisms underlying their anti-cancer activity. Methods: Cur-NPs were synthesised in the form of Cur-PLGA-PEG/chitosan NPs. The effect of Cur-NPs was assessed in HepG2 and Huh 7 LC cells and THLE-2 normal liver cells. Results: The size of synthesised Cur-NPS was determined in the standard range of 141.2 ± 47.5 nm. Compared to THLE-2 cells, LC cells treated with Cur-NPs exerted cytotoxicity at 6.25 μg/mL after 48h. Treatment of HepG-2 cells with 2.5 μg/mL of Cur-NPs inhibited cell migration and this inhibition was augmented at 10 μg/mL (p<0.001). Treatment of chicken embryo with 5 μg/mL Cur-NPs reduced angiogenesis (p<0.001) of 4-day-old embryos. The nanoformulation upregulated Bax and p53 and downregulated Bcl-2 in a concentration-dependent manner and subsequently induce apoptosis in HepG-2 cells. Conclusion: Treatment of LC cells with Cur-NPs decreased cell proliferation, migration, and angiogenesis, and induced cell death by promoting the proapoptotic pathway. [ABSTRACT FROM AUTHOR]

We designed a 3D-printed extracorporeal positioning guide for assisting ultrasound-guided microwave ablation of the liver and observed its effectiveness. 13 patients with liver cancer were selected, and their CT data were obtained. The CT data is reconstructed in 3D by computer software Mimics to create a 3D model. The 3D-printed in vitro positioning guides were designed by 3-Matic and fabricated using 3D printing technology. Finally, it is applied to the clinic, and its effect is observed. The preliminary design of a 3D printed extracorporeal positioning guide was applied to the clinic, and the efficiency of assisted ultrasound positioning was 76.92% (10/13), with three patients requiring repositioning. The efficiency of the 3D printed extracorporeal positioning guide technique was 76.92%, a CT examination was performed one month after surgery, and three patients had residual lesions. 3D-printed extracorporeal positioning guides can assist ultrasound in localizing tumors during liver microwave ablation and reduce repeated punctures. It makes percutaneous microwave ablation of the liver more precise and safe. However, the current study sample is small, there are still apparent shortcomings, and long-term clinical studies are needed to prove its effectiveness. [ABSTRACT FROM AUTHOR]

Background: Transarterial radioembolization (TARE) is used to treat unresectable colorectal cancer with liver metastases (CRCLM). This study aimed to assess survival after TARE and to identify potential prognostic factors in this patient population. Methods: Patients with unresectable and chemorefractory CRCLM treated with TARE at our institution between February 2006 and September 2015 were included in the study. Survival rate, hepatic tumor response, and potential prognostic factors were analyzed. Results: In the 43 study patients, the mean follow-up was 15.0 ± 14.2 months, with a median survival of 13.0 months and 1-, 2-, 3-, 4-, and 5-year survival rates of 52.1%, 24.9%, 21.4%, 21.4%, and 7.1%, respectively. The mean activity of yttrium-90 administered was 1.55 ± 0.28 GBq for the disease-controlled group and 1.19 ± 0.27 GBq for the progressive disease group (p= 0.031). Survival was correlated with Child-Pugh class (p< 0.001), hepatic tumor response (p= 0.001), and baseline carcinoembryonic antigen (CEA) level (p= 0.013). Conclusion: Child-Pugh class B, low degree of hepatic tumor response, and normal baseline CEA levels are prognostic factors for poorer survival after TARE in patients with unresectable and chemorefractory CRCLM. Hepatic tumor response is related to radiation activity delivered to the liver. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) is the most common liver-related cancer and the third leading cause of worldwide cancer-related mortality. There have been many updated guidelines on the management of HCC in the past few years. Given the increasing burden of HCC in clinical practice, knowledge of evidence-based standards of care for these patients is essential for any practitioner managing patients with HCC. Early detection and judicious treatment based on the stage of the HCC can improve patient outcomes. We performed a PubMed (MEDLINE database) search for the latest guidelines related to the screening, detection, diagnosis, staging, and management of HCC. We aim to highlight some major considerations and common mistakes in managing HCC and attempt to provide evidence-based recommendations. The field of HCC management is expected to evolve in the coming years. Increased emphasis on personalized treatment and precision medicine with earlier detection methods, the development of noninvasive diagnostic tools, increased focus on combination therapies and a shift toward more targeted treatments will become more critical. [ABSTRACT FROM AUTHOR]

Liver-dominant metastatic colorectal cancer is noted in approximately 20%–35% of the patients. Systemic chemotherapy remains the first-line treatment for mCRC, but the prognosis is poor due to liver failure. Novel minimally invasive technologies have enabled the optimization of locoregional treatment options. This is a comprehensive review of novel locoregional treatment technologies, both percutaneous ablation and transcatheter arterial treatments, which can be used to decrease hepatic disease progression in patients with mCRC. Trans-arterial radioembolization is the most recently developed locoregional treatment for metastatic liver disease, and robust evidence has been accumulated over the past years. Image-guided techniques, endovascular and ablative, have gained wide acceptance for the treatment of liver malignancies, in selected patients with non-resectable disease. The optimization of dosimetry and microsphere technological advancement will certainly upgrade the role of liver radioembolization segmentectomy or lobectomy in the upcoming years, due to its curative intent. Also, ablative interventions provide local curative intent, offering significant and sustained local tumor control. Standardization protocols in terms of predictability and reliability using immediate treatment assessment and ablation zone software could further ameliorate clinical outcomes. [ABSTRACT FROM AUTHOR]

Essential oils (EOs) obtained from spices, herbs, and medicinal plants are well known in traditional medicine and are an area of interest due to their various biological activities. Therefore, the present study investigates the chemical composition, phytochemical properties, as well as the biological activity of EOs, recovered from un-irradiated and irradiated (2.5, 5, and 10 kGy) caraway seeds. Carum carvi L. seeds were irradiated with gamma irradiation at dose levels 2.5, 5, and 10 kGy, then EOs were recovered from all the samples. The chemical composition, phenols, and flavonoids content were evaluated. As well, antimicrobial and antitumor activities against the two cell lines [colorectal adenocarcinoma (Caco-2) and liver cancer (HepG-2)] were investigated. The results indicated the percentage of oil increased by radiation, especially a dose of 10 kGy, which gave the highest percentage (3.50%) compared to the control. Also, the Gas Chromatography/Mass Spectrometry (GC-MS) analysis revealed the presence of 26 compounds in the essential oil extracts. The main constituent of caraway seeds EOs was Carvone followed by Limonene. According to the results, there was an increase in the content of phenols and flavonoids by using gamma rays compared with control, the maximum increase was observed at dose level 10 kGy (13.70 and 7.38 mg/g oil, respectively) followed by 5 kGy (11.20 and 5.86 mg/g oil, respectively). The antioxidant properties of the caraway essential oils were increased by increasing the irradiation dose level (2.5–10 kGy) analyzed by DPPH radical and metal chelating activity. Caraway essential oils have an antimicrobial action against Gram-positive and Gram-negative bacteria as well as fungi. The antimicrobial activity was increased as the irradiation dose was raised and the10 kGy dose was more effective in suppressing the growth of bacteria and fungi. Additionally, the caraway essential oils have anticancer activity against the two cell lines studied; colorectal adenocarcinoma (Caco-2) and liver cancer cell line (HepG-2) as reduced the cell viability and density. The 10 kGy dose was more effective for oil yield, phenols, flavonoids, and antioxidant activity as well as antibacterial and antifungal activities. Furthermore, the caraway essential oils indicated anticancer activity against the two cell lines studied; colorectal adenocarcinoma (Caco-2) and liver cancer cell line (HepG-2) as reduced the cell viability and density. So caraway could be considered an important herb with multiple therapeutic uses. [ABSTRACT FROM AUTHOR]

Cholangiocarcinomas (CCAs) are a heterogenous group of epithelial malignancies originating at any level of the biliary tree and are subdivided according to their location into intrahepatic (iCCA) and extrahepatic (eCCA). This review provides an updated analysis of studies of genetic characterization of CCA at the level of gene mutation profiling, copy number alterations and gene expression, with definition of molecular subgroups and identification of some molecular biomarkers and therapeutic targets. With the development of genetic sequencing, several driver mutations have been identified and targeted as novel therapeutic approaches, including FGFR2, IDH1, BRAF, NTRK, HER2, ROS, and RET. Furthermore, identification of the cellular and molecular structure of the tumor microenvironment has contributed to the development of novel therapies, such as tumor immunotherapy. Combination therapies of chemotherapy plus targeted molecules or immunotherapy are under evaluation and offer the unique opportunity to improve the outcomes of CCA patients with advanced disease. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) is a frequently occurring malignant gastrointestinal cancer. The 5-year survival rate of HCC is still below 8%, and thus, identifying more effective therapeutic methods is needed. Here, we evaluated the effects of Stigmast-4-en-6β-ol-3-one (S463) on the viability and colony formation of liver cancer cells. S463 treatment decreased the viability and induced apoptosis and ferroptosis in liver cancer cells, and also increased cellular malondialdehyde (MDA) and lipid peroxidation levels. In S463 treated cells, the expression level of Bax was increased, and the expression level of GPX4 was reduced, and the cleavage of PARP was improved. We also found that S463 treatment downregulated E2F1 and upregulated p53 at both the mRNA and protein levels. Importantly, rescue experiments revealed that overexpression of E2F1 partially restored S463-induced Bax and p53 upregulation and GPX4 downregulation and counteracted the S463-induced decrease in cell viability and colony formation and the S463-induced increase in MDA and lipid peroxidation levels. Our findings suggest that S463 significantly inhibits viability and colony formation and induces apoptosis and ferroptosis in liver cancer cells via E2F1. [ABSTRACT FROM AUTHOR]

The characteristics and prognosis of cryptogenic hepatocellular carcinoma (HCC) remain unclear. The albumin-bilirubin (ALBI) grade and its updated version, the easy ALBI (EZ-ALBI) grade, are important prognostic predictors for HCC. We aimed to investigate the long-term survival of patients with cryptogenic HCC and the prognostic role of ALBI and EZ-ALBI grade in these patients. A prospective cohort of 2,937 HCC patients with viral or cryptogenic etiology were retrospectively analyzed. The multivariate Cox model was used to determine prognostic predictors. Cryptogenic HCC patients were often older and diabetic, had lower serum ɑ-fetoprotein (AFP) levels, larger tumor burden, poor performance status, advanced cancer stage, and received non-curative treatments compared with hepatitis B or C-related HCC. The Cox analysis showed that age > 65 years, serum AFP > 400 ng/mL, presence of vascular invasion or distant metastasis, presence of ascites, performance status 2–4, ALBI grade 2 and 3, EZ-ALBI grade 2 and 3, and non-curative treatment, were independent predictors of decreased survival in cryptogenic HCC (p <.001). Significant survival differences were found across ALBI grade and EZ-ALBI grade in cryptogenic HCC and subgroup patients receiving curative or non-curative treatments. The Cancer of Liver Italian Program was the best staging system for patients with cryptogenic HCC. Patients with cryptogenic HCC have a larger tumor burden and advanced cancer stage at disease presentation compared with those with viral HCC. The ALBI and EZ-ALBI score are robust models to evaluate liver functional reserve for these patients independent of treatment modality. [ABSTRACT FROM AUTHOR]

A growing number of studies have suggested that traditional Chinese medicine (TCM) plays an essential role in the development and occurrence of liver cancer. However, the function of Ruangan Lidan decoction (RLD) in liver cancer are not yet adequately identified and manifested, which attracted our attention. The key genes related to liver cancer and RLD and the upstream miRNAs of PDK4 were obtained based on bioinformatics analysis, followed by verification of the targeting relationship between miR-9-5p and PDK4. Next, Huh7 cells were treated with RLD to detect cell proliferation, colony formation, migration, invasion, and apoptosis by multiple assays with gain- and loss-of-function experiments. Moreover, subcutaneous transplanted tumor model and lung metastasis model of liver cancer in nude mice were established to further verify the functional role of RLD in liver cancer growth and metastasis via miR-9-5p/PDK4 axis. Bioinformatics analysis found that PDK4 and miR-9-5p were related to liver cancer, and PDK4 may be a downstream regulator of RLD. miR-9-5p could target and inhibit PDK4. In vitro cell experiments demonstrated that RLD suppressed liver cancer cell proliferation, invasion and migration, and promoted apoptosis by inhibiting miR-9-5p expression and promoting PDK4 expression. In vivo animal experiments further confirmed that RLD inhibited liver cancer growth and metastasis via upregulation of miR-9-5p-dependent PDK4. RLD downregulated miR-9-5p and upregulated PDK4 to inhibit the proliferation, migration, invasion, and induce apoptosis, thereby suppressing the growth and metastasis of liver cancer, highlighting a potential novel target for treatment of liver cancer. [ABSTRACT FROM AUTHOR]

Hepatocellular cancer (HCC) is a serious illness with high prevalence and mortality throughout the whole world. For advanced HCC, immunotherapy is somewhat impactful and encouraging. Nevertheless, a substantial proportion of patients with advanced HCC are still unable to achieve a durable response, owing to heterogeneity from clonal variability and differential expression of the PD-1/PD-L1 axis. Recently, heat shock factor 1 (HSF1) is recognized as an important component of tumor immunotherapeutic response as well as related to PD-L1 expression in cancer. However, the mechanism of HSF1 regulating PD-L1 in cancer, especially in HCC, is still not fully clear. In this study, we observed the significantly positive correlation between HSF1 expression and PD-L1 expression in HCC samples; meanwhile combination expressions of HSF1 and PD-L1 served as the signature for predicting prognosis of patients with HCC. Mechanistically, HSF1 upregulated PD-L1 expression by inducing APOJ expression and activating STAT3 signaling pathway in HCC. In addition, we explored further the potential values of targeting the HSF1-APOJ-STAT3 axis against CD8+ T cells-mediated cancer cells cytotoxicity. These findings unveiled the important involvement of HSF1 in regulating PD-L1 expression in HCC as well as provided a novel invention component for improving the clinical response rate and efficacy of PD-1/PD-L1 blockade. [ABSTRACT FROM AUTHOR]

An unusual NBS promoted cascade reaction of β-anhydroicaritine and alcohols was successfully developed to prepare chromane-3,4-dione 3 in a moderate yield. A mechanism was also put forward to explain this reaction. These chromane-3,4-dione derivatives showed a potent cytotoxicity against HepG2 and MCF-7 cell lines, which were expected to be a potential lead candidate for the treatment of liver cancer and breast cancer. [ABSTRACT FROM AUTHOR]

Current predictors are largely unsatisfied for early recurrence (ER) of hepatocellular carcinoma (HCC) after thermal ablation. We aimed to explore the prognostic value of peripheral immune factors (PIFs) for better ER prediction of HCC after thermal ablation. Patients who received peripheral blood mononuclear cells (PBMCs) tests before thermal ablation were included. Clinical parameters and 18 PIFs were selected to construct ModelClin, ModelPIFs and the hybrid ModelPIFs-Clin. Model performances were evaluated using area under the curve (AUC), and recurrence-free survival (RFS) were analyzed by Kaplan-Meier analysis and log-rank tests. 244 patients were included and were randomly divided in 3:1 ratio to discovery and validation cohorts. Clinical parameters including tumor size and AFP, and PIFs including neutrophils, platelets, CD3+CD16+CD56+ NKT and CD8+CD28- T lymphocytes were selected. The ModelPIFs-Clin showed increase in predictive performance compared with ModelClin, with the AUC improved from 0.664 (95%CI:0.588–0.740) to 0.801 (95%CI:0.734–0.867) in discovery cohort (p < 0.0001), and from 0.645 (95%CI:0.510–0.781) to 0.737(95%CI:0.608–0.865) in validation cohort (p = 0.1006). ModelPIFs-Clin enabled ER risk stratification of patients. Patients predicted in ModelPIFs-Clin high-risk subgroup had a poor RFS compared with those predicted as ModelPIFs-Clin low-risk subgroup, with the median RFS was 18.00 month versus 100.78 month in discovery cohort (p < 0.0001); and 24.00 month versus 60.35 month in validation cohort (p = 0.288). Patients in different risk subgroups exhibited distinct peripheral immune contexture. Peripheral immune cells aiding clinical parameters boosted the prediction ability for ER of HCC after thermal ablation, which be helpful for pre-ablation ER risk stratification. [ABSTRACT FROM AUTHOR]

Aflatoxins are types of mycotoxins that can cause acute and chronic toxicity in human. In general, there are four types of aflatoxinsB1, B2, G1 and G2, which among them aflatoxin B1 is the most potent carcinogen in animal species and causes liver cancer. The goal of this study was to evaluate of aflatoxin concentration in legumes samples marketed in Tehranbya high-performance liquid chromatography (HPLC). Fifty samples of legumes including peas, red beans, lentils, mung bean and cotyledons (n = 10 of pea, n = 10 of red bean, n = 10 of lentils, n = 10 of mung bean and n = 10 of cotyledons) were obtained from different regions (bulk legumes) of Tehran city in Iran and different packaging brands that had the highest supply in Tehran stores and were transported to the laboratory under appropriate conditions to measure aflatoxin (B1, B2, G1, G2 and total). Considering the limit of detection (LOD) of the current study, the aflatoxin level of all samples of peas, red beans, lentils, mung bean and cotyledons samples was lower than LOD. Based on the results, it can be concluded that the consumption of legumes in Tehran city by consumers can be safe, but more research is needed to avoid potential risks, and also routine and periodic monitoring of aflatoxin levels in legumes is recommended. [ABSTRACT FROM AUTHOR]

The systemic drug has historically been preferred for the treatment of the majority of pathological conditions, particularly liver cancer. Indeed, this mode of treatment is associated with adverse reactions, toxicity, off-target accumulation, and rapid hepatic and renal clearance. Numerous efforts have been made to design systemic therapeutic carriers to improve retention while decreasing side effects and clearance. Following systemic medication, local administration of therapeutic agents allows for higher 'effective' doses with fewer side effects, kidney accumulation, and clearance. Hydrogels are highly biocompatible and can be used for both imaging and therapy. Hydrogel-based drug delivery approach has fewer side effects than traditional chemotherapy and can deliver drugs to tumors for a longer time. The chemical and physical flexibility of hydrogels can be used to achieve disease-induced in situ accumulation as well as subsequent drug release and hydrogel-programmed degradation. Moreover, they can act as a biocompatible depot for localized chemotherapy when stimuli-responsive carriers are administrated. Herein, we summarize the design strategies of various hydrogels used for localized chemotherapy of liver cancer and their delivery routes, as well as recent research on smart hydrogels. [ABSTRACT FROM AUTHOR]

A series of novel 9-O-substituted-13-octylberberine derivatives were designed, synthesised and evaluated for their anti-hepatocellular carcinoma (HCC) activities. Compound 6k showed the strongest activity against three human hepatoma cells including HepG2, Sk-Hep-1 and Huh-7 cells with IC50 values from 0.62 to 1.69 µM, which were much superior to berberine (IC50 >50 µM). More importantly, 6k exhibited lower cytotoxicity against normal hepatocytes L-02 with good lipid-water partition properties. The mechanism studies revealed that 6k caused G2/M phase arrest of the cell cycle, stabilised G-quadruplex DNA, and induced apoptosis via a mitochondrial apoptotic pathway. Finally, the in vivo anti-HCC activity of 6k was validated in the H22 liver cancer xenograft mouse model. Collectively, the current study would provide a new insight into the discovery of novel, safe and effective anti-HCC agents. [ABSTRACT FROM AUTHOR]

Compound K (CK) is the metabolite and final active ingredient of diol-type ginsenosides. In this study, we investigated the effect of CK on mitochondrial apoptosis in SMMC-7721 and BEL-7404 cells and the regulatory mechanism through in vitro and in vivo experiments. The results demonstrated that CK inhibited Hepatocellular carcinoma (HCC) cells proliferation and arrested the cells in G0/G1 phase. CK induces mitochondrial apoptosis in HCC cells and inhibited p-ERK expression. Bcl-2 associated transcription factor 1 (Bclaf1) was distributed in the nucleus and cytoplasm, and CK inhibited its expression. Treatment of a nude mouse xenograft model bearing SMMC-7721 cells with CK decreased the expression of Bclaf1, p-ERK, and Bcl-2 but increased that of Bax. In summary, ginsenoside CK downregulated Bclaf1 expression, inhibited the activation of the ERK pathway, and triggered mitochondrial apoptosis in HCC. These findings uncovered a potential therapeutic strategy leveraging the anti-tumor effects of CK against HCC. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) is associated with a high mortality rate. In this study, we aimed to investigate the therapeutic effect and safety of hepatic arterial administration of doxorubicin (Dox)-loaded hollow gold nanospheres (Dox@HAuNSs) combined with photothermal ablation (PTA) in a rabbit VX2 liver cancer model established by implanting VX2 tumour cells into rabbit livers. Rabbits were randomly divided into four treatment groups: physiological saline solution (control); lipiodol and doxorubicin (Dox + Lp); lipiodol and Dox@HAuNS (Dox@PEG-HAuNS + Lp); and lipiodol, Dox@PEG-HAuNS, and photothermal ablation (Dox@PEG-HAuNS + Lp + PTA). Dox release from Dox@PEG-HAuNS in the tumour was detected using fluorescence microscopy. Tumour size and liver-kidney function were assessed in each rabbit preoperatively and on postoperative days 3, 7, and 14. Necrosis, proliferation, and micro-vessel density of VX2 tumours were estimated in peripheral tumour tissues. Dox release from Dox@PEG-HAuNS was increased with a subsequent increase in tumour necrosis in liver tumours after PTA, whereas the tumour volume and proliferation decreased. However, the aspartate aminotransferase and alanine aminotransferase levels indicated transient liver damage. Thus, intra-arterial delivery of Dox@PEG-HAuNS combined with PTA can suppress VX2 liver cancer growth. Dox@PEG-HAuNS + Lp + PTA is also associated with transient liver damage in rabbits. The combination of Dox@PEG-HAuNS chemoembolisation and PTA could be a potential therapeutic approach for HCC and it has broad application prospects. [ABSTRACT FROM AUTHOR]

Fish represents one of the most important dietary sources of omega-3 polyunsaturated fatty acids, which are known to be associated with various health benefits. This study aimed to systematically review existing meta-analyses of observational studies exploring the association between fish intake and various health outcomes. A systematic search of electronic databases was conducted to retrieve a total of 63 studies. Evidence was deemed as possible for the association between higher fish intake and decreased risk of the acute coronary syndrome, liver cancer, and depression, and limited for other outcomes (including age-related macular degeneration, Alzheimer's disease, heart failure, all-cause and coronary heart disease mortality, total and ischaemic stroke) due to heterogeneity between results and potential otherwise inexplicable confounding factors. In conclusion, results from epidemiological studies support the mechanistic effects associated with omega-3 fatty acids from high fish consumption, but evidence needs to be further corroborated with more reliable results. [ABSTRACT FROM AUTHOR]

Finland is among the countries with low hepatitis B endemicity. We evaluate the hepatitis B-related disease and economic burden needed for evidence-based immunisation policy decision-making. Hepatitis B-related cases in 2004–2012 were retrieved from population-based nationwide registers. We evaluated the incidence, health care resource use, health care costs, and life years lost due to hepatitis B-related outcomes. An episode of care was constructed from each individual's hepatitis B-related events retrieved from individually linkable registers. The mean health care costs per an acute hepatitis B case were €450 (SD 240), €2030 (SD 350), and €5400 (SD 3370) in those aged 0–14, 15–64, and ≥65 years, respectively. For chronic infection, the mean cost per case among Finnish-born individuals was €990 and among foreign-born €1360. The costs per case of liver cirrhosis were €15,350 and liver cancer €19,080. In addition, the annual antiviral medication costs per case receiving antiviral medication were €4710 to €5530. Annually <10% of the chronic and approximately 20% of liver cirrhosis cases received antiviral medication. We identified annually 21 acute, 264 chronic, three liver cirrhosis, and four liver cancer cases and 63.7 life years lost due to hepatitis B per 5.3 million inhabitants. The total annual health care costs were €1.2 million of which 60% were antiviral medication costs and 86% accounted for chronic hepatitis B. When planning prevention of hepatitis B infection, it is pivotal to notice that the overall disease and economic burden due to hepatitis B is mostly due to chronic infection. [ABSTRACT FROM AUTHOR]

Purpose: Radiofrequency ablation (RFA) and microwave ablation (MWA) are the two main percutaneous techniques for the treatment of unresectable hepatocellular carcinoma (HCC). However, to date, studies comparing the two therapies have provided discordant results. The aim of this meta-analysis is to evaluate the efficacy and safety of the two treatments for HCC patients.Materials and methods: A computerised bibliographic search was performed on PubMed/MEDLINE, Embase, Google Scholar and Cochrane library databases. The rates of complete response (CR), local recurrence (LRR), 3-year survival (SR) and major complications were compared between the two treatment groups by using the Mantel-Haenszel test in cases of low heterogeneity or the DerSimonian and Laird test in cases of high heterogeneity. Sources of heterogeneity were investigated using subgroup analyses. In order to confirm our finding, sensitivity analysis was performed restricting the analysis to high-quality studies.Results: One randomised controlled trial (RCT) and six retrospective studies with 774 patients were included in the meta-analysis. A non-significant trend of higher CR rates in the patients treated with MWA was found (odds ratio (OR) = 1.12, 95% confidence interval (CI) 0.67–1.88,p = 0.67]. Overall LRR was similar between the two treatment groups (OR 1.01, 95% CI 0.53–1.87,p = 0.98) but MWA outperformed RFA in cases of larger nodules (OR 0.46, 95% CI 0.24–0.89,p = 0.02). 3-year SR was higher after RFA without statistically significant difference (OR 0.95, 95% CI 0.58–1.57,p = 0.85). Major complications were more frequent, although not significantly, in MWA patients (OR 1.63, 95% CI 0.88–3.03,p = 0.12).Conclusions: Our results indicate a similar efficacy between the two percutaneous techniques with an apparent superiority of MWA in larger neoplasms. [ABSTRACT FROM AUTHOR]

Hepatocyte-specific knockout of the essential autophagy gene Autophagy-related 7 (Atg7) is sufficient to cause hepatic carcinogenesis. A recent paper by Lee et al. unveils the molecular pathway accounting for hepatic hypertrophy and hyperplasia followed by malignant transformation. This pathway involves the overactivation of the transcription factor yes-associated protein (YAP), which turns out to be an autophagic substrate. Of note, the transcriptional signature activated in mouse hepatocytes lacking Atg7 resembles that found in non-alcoholic steatohepatitis (NASH), as well as in the steatohepatitic subtype of human hepatocellular carcinomas. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC), a major primary liver cancer, is one of the most lethal malignancies worldwide. Increasing evidence has demonstrated that chromobox protein homolog 3 (CBX3) functions as an oncogene in different cancers. However, its expression profiles and biological functions in HCC remain unknown. Data on CBX3 expression in HCC acquired from the GEO and TCGA databases were analyzed. The biological functions of CBX3 in HCC were examined by in vitro experiments. Bioinformatics analysis, qRT-PCR and western blotting were performed to explore the mechanism of CBX3 in HCC. CBX3 mRNA was upregulated in HCC tissues, and overexpression of CBX3 mRNA was negatively correlated with malignancies and poor prognosis in HCC patients. CBX3 knockdown decreased growth, migration and invasion of HCC cells in vitro. Moreover, bioinformatics analysis and experimental observation indicated that CBX3 expression was correlated with cell cycle regulatory proteins in HCC cells. Finally, starBase predicted that miR-139 could directly target CBX3 in HCC. Confirmatory experiments verified that miR-139 overexpression attenuated HCC cell proliferation and migration, and these effects could be reversed by overexpressing CBX3. Our results showed that the miR-139/CBX3 axis may be involved in HCC development by regulating cell cycle progression and may be a promising target in the treatment of HCC. [ABSTRACT FROM AUTHOR]

The selectivity of chemotherapeutic agents for liver cancer is poor. When they kill tumour cells, they produce serious adverse reactions in the whole body and multidrug resistance (MDR) is also a major hurdle in liver cancer chemotherapy. Combination therapy is a useful method for overcoming MDR and reducing toxic and side effects. In this study, we developed a long-circulating codelivery system, in which doxorubicin (DOX) and schizandrin A (SchA) are combined against MCF-7/ADR cells. The DOX-SchA long-circulating liposome (DOX-SchA-Lip) was prepared using ammonium sulphate gradient method. The two drugs were co-encapsulated into the distearoyl phosphatidylethanolamine-polyethylene glycol (DSPE-mPEG2000) liposome and the liposome had an average particle size of (100 ± 3.5) nm and zeta electrical potential of (–31.3 ± 0.5) mV. The average encapsulation rate of DOX was 97.98% and that of SchA was 86.94%. DOX in liposome had good sustained-release effect. The results showed that DOX-SchA-Lip could significantly prolong the half-life (t1/2z) of the DOX and SchA, increase their circulation time in vivo, improve its bioavailability and reduce their side effects. Liposome can effectively induce early apoptosis of HepG2/ADR cells and the cell cycle was blocked in S-phase by DOX-SchA-Lip in a dose-dependent manner. The IC50 of compound liposome to HepG2 and HepG2/ADR were 0.55 μmol/L and 1.38 μmol/L, respectively, which could significantly reverse the resistance of HepG2/ADR and the reversion multiple was 30.28. It was verified that DOX-SchA-Lip can effectively kill tumour cells and reverse MDR. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) has a poor prognosis, related, in part, to frequent late-stage diagnosis. Improved implementation of effective HCC surveillance is critical to reduce HCC mortality. We performed a targeted literature review to identify intervention targets for improving HCC surveillance effectiveness, including enriched risk stratification tools, improved surveillance tools with higher accuracy for early HCC detection, and increasing surveillance adherence. HCC surveillance has been demonstrated to be efficacious in several cohort studies but has lower surveillance effectiveness in clinical practice. HCC surveillance is currently recommended in all patients with cirrhosis, and improved risk stratification using clinical risk scores, genetic scores, and novel biomarkers are important to move from a 'one-size-fits-all' strategy to one more aligned with values of precision medicine. Current surveillance modalities, ultrasound, and AFP, miss over one-third of HCC at an early stage and are associated with potential surveillance harms, underscoring a need for alternative surveillance strategies with higher accuracy. MRI- and biomarker-based surveillance strategies have promising early data in phase II studies but require validation in phase III cohorts before routine use in practice. Finally, surveillance is underused in clinical practice, highlighting a need for intervention strategies to increase utilization. [ABSTRACT FROM AUTHOR]

To examine conditional survival (CS) in patients with non‐metastatic intrahepatic cholangiocarcinoma (nmICC) after surgical treatment according to pT and pN stages. A total of 608 patients were included. Conditional three-year cancer-specific mortality estimates were obtained according to pT and pN stages. Multivariable Cox regression analysis was applied to predict factors affecting cancer-specific mortality (CSM). According to substages based on pT and pN status, 109 patients (17.9%) with pT1aN0, 96 (15.8%) with pT1bN0, 205 (33.7%) with pT2N0, 82(13.5%) with pT3-5N0, and 116 (19.1%) with pTanyN1 were identified. Conditional CSM-free estimates increased from 75% to 87%, 66% to 70%, 53% to 86%, and 36 to 54% after three years of event-free follow-up in pT1b, pT2, pT3-4N0, and pTanyN1 patients, respectively, whereas it decreased from 87% to 79% in pT1aN0 patients. Based on multivariable analysis, patients with pT2N0 (hazard ratio [HR] 2.0 p <.01), pT3-4N0 (HR 2,7 p <.01), and pTanyN1-3 (HR 4.8 p <.01) had higher CSM than patients with pT1aN0 at baseline. CS varied across stage categories in nmICC patients after surgery, and it was important in individualized clinical counseling and decision‐making for nmICC. [ABSTRACT FROM AUTHOR]

Novel 3′-[4-fluoroaryl-(1,2,3-triazol-1-yl)]-3′-deoxythymidine analogues (7a-l) were developed by the Cu alkyne-azide cycloaddition (CuAAC) reaction. The obtained lead compounds were confirmed by using 1H NMR, 13C NMR, 2 D NMR, HRMS and their anticancer activities were screened against Huh-7 liver cancer cells and U87MG human glioblastoma cells. Among the synthesized fluorinated 1,2,3-triazolyl nucleosides, three compounds (7i, 7a-b) demonstrated promising anti-proliferative against Huh-7 and U87MG cell lines. Significantly, compound 7i has displayed remarkable promising anticancer activity with IC50 value in the micromole range (22.41–24.92 µM) and (18.12–21.36 µM) against Huh-7 cancer cells and U87MG glioblastoma cells, respectively. [ABSTRACT FROM AUTHOR]