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A Low-Cost Flash Photographic System for Visualization of Droplets in Drop-on-Demand Inkjet
摘要： Hepatocellular carcinoma (HCC) is one of the most common and deadly human cancers. The 5-year survival rate is very low. Unfortunately, there are few efficacious therapeutic options. Until recently, Sorafenib has been the only available systemic drug for advanced HCC. However, it has very limited survival benefits, and new therapies are urgently needed. In this study, we investigated the anti-HCC activity of carfilzomib, a second-generation, irreversible proteasome inhibitor, as a single agent and in combination with sorafenib. In vitro, we found that carfilzomib has moderate anticancer activity toward liver cancer cells, but strongly enhances the ability of sorafenib to suppress HCC cell growth, proliferation, migration, invasion, and survival. Remarkably, the drug combination exhibits even more potent antitumor activity when tested in animal tumor models. Mechanistically, the combined treatment activates caspase-dependent and endoplasmic reticulum stress/CHOP-mediated apoptotic pathways, and suppresses epithelial–mesenchymal transition. In conclusion, our results demonstrate that the combination of carfilzomib and sorafenib has synergistic antitumor activities against HCC, providing a potential therapeutic strategy to improve the mortality and morbidity of HCC patients.
关键词： Hepatocellular Carcinoma,Proteasome Inhibitor,ER Stress,Apoptosis,Sorafenib,EMT,Carfilzomib,Synergistic Inhibition
更新于2025-09-23 15:23:52
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An fluorescent aptasensor for sensitive detection of tumor marker based on the FRET of a sandwich structured QDs-AFP-AuNPs
摘要： The detection of alpha-fetoprotein (AFP) is of great importance for hepatocellular carcinoma (HCC) diagnosis, but it needs to be further improved because of poor sensitivity and complicated operating steps. In this paper, a simple and sensitive homogeneous aptasensor for AFP has been developed based on F?rster resonance energy transfer (FRET) where the AFP aptamer labeled luminescent CdTe quantum dots (QDs) as a donor and anti-AFP antibody functional gold nanoparticles (AuNPs) as an acceptor. In the presence of AFP, the bio-affinity between aptamer, target, and antibody made the QDs and AuNPs close enough, thus the fluorescence of CdTe QDs quenched though the FRET between QD and AuNP. The fluorescent aptasensor for AFP showed a concentration-dependent decrease of fluorescence intensity in the low nanomolar range and a detecting linear range of 0.5-45 ng mL?1, with a detection limit of 400 pg mL?1. Moreover, this homogeneous aptasensor is simple and reliable, and obtained satisfying results for the detection of AFP in human serum samples. With more and more aptamers for biomarkers have been selected gradually, this approach could be easily extended to detection of a wide range of biomarkers. The proposed aptasensor has great potential for carcinoma screening in point-of-care testing and even in field use.
关键词： alpha fetoprotein (AFP),fluorescent aptasensor,biomarker,hepatocellular carcinoma,F?rster resonance energy transfer (FRET)
更新于2025-09-23 15:23:52
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Endoscopic Cerenkov luminescence imaging and image-guided tumor resection on hepatocellular carcinoma-bearing mouse models
摘要： Detecting deep tumors inside living subject is still challenging for Cerenkov luminescence imaging (CLI). In this study, a high-sensitivity endoscopic CLI (ECLI) system was developed with a dual-mode deep cooling approach to improve the imaging sensitivity. System was characterized through a series of ex vivo studies. Furthermore, subcutaneous and orthotropic human hepatocellular carcinoma (HCC) mouse models were established for ECLI guided tumor resection in vivo. The results showed that the ECLI system had spatial resolution (62.5 μm) and imaging sensitivity (6.29×10-2 kBq/μl 18F-FDG). While the results from both subcutaneous and orthotropic HCC mouse models demonstrate the effectiveness of the system to intraoperatively guide the surgery of deep tumors such as liver cancer. Overall, the developed system exhibits promising potential for the applications of tumor precise resection and novel nanoprobe based optical imaging.
关键词： Endoscopy,Image-guided surgery,Hepatocellular carcinoma (HCC),Cerenkov luminescence imaging
更新于2025-09-23 15:22:29
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Evaluation Efficacy of Rhenium-188 loaded micro-particles for Radiotherapy in a Mouse Model of Hepatocellular Carcinoma
摘要： Hepatocellular carcinoma (HCC) is one of the leading causes of mortality worldwide. The aim of the present study was to evaluate the distribution and the therapeutic effect of 188Re-Tin-colloid micro-particles in subcutaneous HCC-bearing mice. The synthesis and characterization of micro-particles labeled with 188Rhenium isotope were performed. The micro-particles were injected into the tumor site subcutaneously in the BNL HCC-bearing mice, with three treatment groups: normal saline, 188Re micro-particles, and 188Re-Tin-colloid micro-particles. The results of biodistribution showed that major radioactivity (188Re) of 188Re-Tin-colloid micro-particles (18.69 ± 4.28 %ID/g) remained at the tumor sites, compared with 188Re micro-particles (0.21 ± 0.12 %ID/g) post injection 24 h. Following the injection of 188Re-Tin-colloid micro-particles for 14 days, all BNL tumor in mice were regression during the observation period. By contrast, all of the mice treated with normal saline or 188Re micro-particles had died by 24 and 28 days, respectively. The 188Re-Tin-colloid micro-particles demonstrated high accumulation and therapeutic potential in the subcutaneous HCC-bearing mice.
关键词： 188Re,Hepatocellular carcinoma,colloid,micro-particles
更新于2025-09-19 17:15:36
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Investigation of copper-cysteamine nanoparticles as a new photosensitizer for anti-hepatocellular carcinoma
摘要： Hepatocellular carcinoma (HCC) is a primary malignancy of the liver and occurs predominantly in patients with underlying chronic liver disease and cirrhosis. HCC is now the third leading cause of cancer deaths worldwide, with over 500,000 people affected. However, there is no complete effective (ideal) treatment for liver cancer yet, and the new methods are expected to be discovered. Herein, for the first time, we report the anti-HCC effects of copper-cysteamine nanoparticles (Cu-Cy NPs), a new type of photosensitizers. An in vitro 3-(4,5-dimethylthiazol- 2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay shows that Cu-Cy NPs could significantly reduce the activity of HepG2 cells at a very low dose after a short time of ultraviolet radiation. In addition, we found that cell death was induced by Cu-Cy NPs, which is associated with cellular apoptosis. This implied that apoptosis might be the main mechanism of the Cu-Cy’s anti-HCC activity. Furthermore, we found that Cu-Cy NPs obviously inhibited the tumor growth in vivo. More interestingly, we found that the soluble Cu-Cy NPs were able to enter exosomes which were secreted by tumor cells, and exosomes could be used to deliver Cu-Cy NPs to target tumor cells. All these observations suggest that Cu-Cy NPs have a good potential for cancer treatment.
关键词： copper-cysteamine,Hepatocellular carcinoma,nanoparticles,photosensitizer,photodynamic therapy
更新于2025-09-19 17:15:36
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Clinical application of indocyanine green-fluorescence imaging during hepatectomy
摘要： In hepatobiliary surgery, the fluorescence and bile excretion of indocyanine green (ICG) can be used for real-time visualization of biological structure. Fluorescence cholangiography is used to obtain fluorescence images of the bile ducts following intrabiliary injection of 0.025?0.5 mg/mL ICG or intravenous injection of 2.5 mg ICG. Recently, the latter technique has been used in laparoscopic/robotic cholecystectomy. Intraoperative fluorescence imaging can be used to identify subcapsular hepatic tumors. Primary and secondary hepatic malignancy can be identified by intraoperative fluorescence imaging using preoperative intravenous injection of ICG through biliary excretion disorders that exist in cancerous tissues of hepatocellular carcinoma (HCC) and in non-cancerous hepatic parenchyma around adenocarcinoma foci. Intraoperative fluorescence imaging may help detect tumors to be removed, especially during laparoscopic hepatectomy, in which visual inspection and palpation are limited, compared with open surgery. Fluorescence imaging can also be used to identify hepatic segments. Boundaries of hepatic segments can be visualized following injection of 0.25?2.5 mg/mL ICG into the portal veins or by intravenous injection of 2.5 mg ICG following closure of the proximal portal pedicle toward hepatic regions to be removed. These techniques enable identification of hepatic segments before hepatectomy and during parenchymal transection for anatomic resection. Advances in imaging systems will increase the use of fluorescence imaging as an intraoperative navigation tool that can enhance the safety and accuracy of open and laparoscopic/robotic hepatobiliary surgery.
关键词： liver resection,colorectal liver metastasis (CRLM),Indocyanine green (ICG),hepatocellular carcinoma (HCC),fluorescence imaging,intraoperative cholangiography
更新于2025-09-11 14:12:44
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A pH-Responsive Glycyrrhetinic acid-Modified Small Molecular Conjugate for NIR Imaging of Hepatocellular Carcinoma (HCC)
摘要： Herein, we reported a glycyrrhetinic acid (GA)-decorated small molecule conjugate for pH-triggered near infra-red (NIR) fluorescence imaging of hepatocellular carcinoma (HCC). Our ‘‘in vitro’’ studies demonstrated that NIR-GA was efficiently up-taken by liver cancer cell lines such as HepG2 and Huh7 through GA receptors-mediated endocytic pathway. As suggested by co-localization studies, NIR-GA mainly localized into the lysosome where acidic pH results in activation of fluorescent dye via H+-triggered spirolactam ring opening to give strong fluorescence in NIR region.
关键词： pH-responsive,Changsha dye,Near-infrared,Glycyrrhetinic acid,Hepatocellular carcinoma
更新于2025-09-10 09:29:36
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Detection of Alpha-Fetoprotein in Hepatocellular Carcinoma Patient Plasma with Graphene Field-Effect Transistor
摘要： The detection of alpha-fetoprotein (AFP) in plasma is important in the diagnosis of hepatocellular carcinoma (HCC) in humans. We developed a biosensor to detect AFP in HCC patient plasma and in a phosphate buffer saline (PBS) solution using a graphene field-effect transistor (G-FET). The G-FET was functionalized with 1-pyrenebutyric acid N-hydroxysuccinimide ester (PBASE) for immobilization of an anti-AFP antibody. AFP was detected by assessing the shift in the voltage of the Dirac point (?VDirac) after binding of AFP to the anti-AFP-immobilized G-FET channel surface. This anti-AFP-immobilized G-FET biosensor was able to detect AFP at a concentration of 0.1 ng mL?1 in PBS, and the detection sensitivity was 16.91 mV. In HCC patient plasma, the biosensor was able to detect AFP at a concentration of 12.9 ng mL?1, with a detection sensitivity of 5.68 mV. The sensitivity (?VDirac) depended on the concentration of AFP in either PBS or HCC patient plasma. These data suggest that G-FET biosensors could have practical applications in diagnostics.
关键词： alpha-fetoprotein,biosensor,graphene,hepatocellular carcinoma,field-effect transistor
更新于2025-09-10 09:29:36
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Development of up-converting phosphor technology-based lateral flow assay for quantitative detection of serum PIVKA-II: Inception of a near-patient PIVKA-II detection tool
摘要： Background: Development of a test card based on up-conversion phosphor technology-based immune lateral flow (UPT-LF) assay as a near-patient detection tool for serum Prothrombin induced by vitamin K absence or antagonist II (PIVKA-II). Methods: Up-converted phosphor nanoparticles (UCPs) were used to bind to PIVKA-II monoclonal antibodies as labeled probes to develop the test card for detecting serum PIVKA-II. The UPT-LF test card was evaluated by the limit of detection, linearity, stability, recovery rate, precision and interference. Preliminary clinical validation was conducted by detection of 498 serum samples from 228 patients with hepatocellular carcinoma (HCC), 170 patients with liver benign lesion (LBL) and 100 healthy controls (HC). Additionally, the correlation of serum PIVKA-II detection between UPT-LF assay and Chemiluminescence enzyme immunoassay (CLEIA) assay were performed. Results: Modified and activated UCPs bound to monoclonal antibodies powerfully to form the luminescent labeled probes. Limit of detection and linear range of UPT-LF test card for serum PIVKA-II were 2.66 and 4.8–20,000 ng/ml, respectively. Test card had good 25 °C thermal and 4 °C validity period stability, 93.1%–99.2% of recovery rate, 2.6–5.8% and 5.4–8.9% of intra-assay and inter-assay CVs, and strong anti-interference ability for 8 common serum analytes. The sensitivity and specificity (vs LBL + HC group) of test card for HCC were 71.5% and 88.9%, respectively. The R2 between UPT-LF assay and CLEIA assay was 0.901. Conclusions: UPT-LF assay provides a reliable, rapid and convenient test for quantitative detection of serum PIVKA-II as well as diagnosis of HCC by a point of care testing way.
关键词： Point of care testing,Hepatocellular carcinoma,PIVKA-II,Lateral flow assay,Up-conversion phosphor technology
更新于2025-09-10 09:29:36
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Label-free detection of liver cancer based on silver nanoparticles coated tissue surface-enhanced Raman spectroscopy
摘要： Surface-enhanced Raman spectroscopy (SERS) was employed to obtain hepatocellular carcinoma (HCC) tissue spectra with coated silver nanoparticles. Principal component analysis (PCA) combined with linear discriminate analysis (LDA) was introduced to analyze the obtained spectra. The sensitivity and specificity of discrimination for HCC and normal group is 93.8% and 100%. While that is 79.2% and 93.8% for HCC and adjacent HCC group, this study suggests a great potential method for early HCC detection by combination of silver nanoparticles based tissue SERS and PCA-LDA analysis.
关键词： silver nanoparticles,surface-enhanced Raman spectroscopy (SERS),linear discriminate analysis,hepatocellular carcinoma,principal component analysis
更新于2025-09-09 09:28:46