IMMUNITY
·
2021
·
IF 31.745
Wenjie Zhang,Guangyan Zhangyuan,Fei Wang,Kangpeng Jin,Haiyuan Shen,Liansheng Zhang,Xiang Yuan,Jincheng Wang,Haitian Zhang,Weiwei Yu,Ruyi Huang,Xiaoliang Xu,Yin Yin,Guisheng Zhong,Anning Lin,Beicheng Sun
Summary Chronic inflammation plays a central role in hepatocellular carcinoma (HCC), but the contribution of hepatocytes to tumor-associated inflammation is not clear. Here, we report that the zinc finger transcription factor Miz1 restricted hepatocyte-driven inflammation to suppress HCC, independently of its transcriptional activity. Miz1 was downregulated in HCC mouse models and a substantial fraction of HCC patients. Hepatocyte-specific Miz1 deletion in mice generated a distinct sub-group of hepatocytes that produced pro-inflammatory cytokines and chemokines, which skewed the polarization of the tumor-infiltrating macrophages toward pro-inflammatory phenotypes to promote HCC. Mechanistically, Miz1 sequestrated the oncoprotein metadherin (MTDH), preventing MTDH from promoting transcription factor nuclear factor κB (NF-κB) activation. A distinct sub-group of pro-inflammatory cytokine-producing hepatocytes was also seen in a subset of HCC patients. In addition, Miz1 expression inversely correated with disease recurrence and poor prognosis in HCC patients. Our findings identify Miz1 as a tumor suppressor that prevents hepatocytes from driving inflammation in HCC.
研究领域:
肿瘤学
·
分子生物学
·
免疫学
·
细胞生物学
✓ 已验证
DOI
PubMed
高影响因子
NEW JOURNAL OF CHEMISTRY
·
2021
·Vol. 45
·期 19
·8608-8618
·
IF 3.591
Min Chen,Haimei Li,Xueming Su,Runqiang Wu,Huafu Feng,Xiaohang Shi,Jintao Liang,Jiejing Chen,Guiyin Li
Glypican-3 (GPC3) is a potential hepatocellular carcinoma (HCC) serum marker with good sensitivity and specificity. Herein, a label-free electrochemical aptasensor for the detection of GPC3 was developed using a reduced graphene oxide–hemin–chitosan (RGO–H–CS) nanocomposite-modified screen-printed electrode (SPE) as a biosensing platform and GPC3 aptamer as the recognition element. When GPC3 was present, the aptamer could specifically bind with the target GPC3 by specific recognition reaction and form GPC3–aptamer conjugations on the sensing surface, which could alter the electrochemical redox signal of hemin (Fe(III)/hemin(Fe(II))) in the RGO–H–CS nanocomposite recorded by differential pulse voltammetry (DPV). The electrochemical GPC3 aptasensor was characterized via scanning electron microscopy (SEM), Raman spectroscopy, cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS). Under optimal conditions, currents originating from the oxidation of hemin had a linear relationship with the concentration of GPC3 in the range of 0.01 µg mL−1 to 10.0 µg mL−1 with a detection limit of 7.9 ng mL−1 (S/N = 3). The developed aptasensor was applied to detect the GPC3 level in the human serum samples with the recovery rate of 101.04–104.9%. Moreover, the label-free aptasensor exhibited considerable anti-interfering ability, acceptable stability and good reproducibility. Therefore, this study provides a reliable and objective analysis method to achieve high screening for the early diagnosis of HCC.
研究领域:
生物传感器
·
癌症诊断
·
电化学
·
纳米技术
·
分析化学
✓ 已验证
产品关联
DOI
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2019
·
IF 4.784
Guobao Chen,Runan Wei,Xiang Huang,Fuping Wang,Zhongmin Chen
Transcatheter arterial chemoembolization (TACE) is well known as an effective treatment for hepatocellular carcinoma (HCC). In the present study, a novel embolic agent of sodium alginate (SA)-modified silk fibroin (SF) microspheres was successfully prepared by emulsifying cross-linking method. The SA-modified SF microspheres were evaluated for the ability of embolization by investigating the morphology, particle size, swelling ratio, degradation, cytotoxicity, blood compatibility, and in vivo embolization. The results found that SA-modified SF microspheres had smooth surfaces and good sphericity. Swelling ratio of the microspheres can meet the requirements of arterial embolic agent and have pH and temperature sensitivity. Furthermore, hemolytic and anticoagulant studies have proved that the microspheres have good blood compatibility. Cytotoxicity tests indicated that the microspheres could promote the proliferation of fibroblasts and HUVEC. In vivo embolization evaluation of microspheres revealed that the arteries could be embolized by SA-modified SF microspheres in 3 weeks. The ability of drug loading and releasing of microspheres was proved by the controlled release profile of Adriamycin hydrochloride. The findings indicated that the SA-modified SF microspheres can be used as a potentially biodegradable arterial embolic agent for liver cancer therapy.
研究领域:
生物医学工程
·
药学
·
癌症研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2025
·
IF 11.5
Xing Gao,Hongwei Cheng,Minglei Teng,Hongrui Zhang,Hu Chen,Songnan Qu,Gang Liu
Transcatheter arterial chemoembolization (TACE) is the principal treatment option for patients with unresectable hepatocellular carcinoma (HCC). However, the hypoxic microenvironment following TACE can promote angiogenesis and suppress tumor ferroptosis, resulting in an unfavorable prognosis. Tirapazamine (TPZ), a hypoxia-activated prodrug with specific cytotoxicity for hypoxic cells, making it a potential candidate for TACE. To develop an effective hypoxia-responsive drug delivery platform for TACE, we propose a novel lipiodol embolic formulation that integrates TPZ and sorafenib (SFB) by super-stable homogeneous intermixed formulation technology (SHIFT). This approach achieves the manufacture of embolic agents with stable drug dispersion characteristics, fulfilling the need for sustained drug release in TACE. The prolonged tumor penetration of TPZ exhibited embolization-responsive tumor killing, and its combination with SFB can suppress hypoxia-induced angiogenesis and trigger tumor ferroptosis, maintaining low oxygen levels, thereby boosting the therapeutic efficacy of TPZ. Conversely, TPZ can combat the resistance to SFB in hypoxic tumor cells. In summary, this study developed a novel embolization drug formulation based on embolic hypoxic microenvironment. The synergistic mechanism of TPZ and SFB enhances the therapeutic effects of hypoxia-activated prodrugs and mitigates the adverse effects of hypoxia.
研究领域:
肿瘤学
·
药理学
·
介入放射学
·
药物递送系统
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Cancers
·
2025
·Vol. 18
·期 1
·92
·
IF 4.4
Hao Dong,Yuan Gao,Dongyue Jiang,Chenjie Feng,Xinyue Gu,Xiyunyi Cai,Yulin Liu,Guangyu Zhang,Jiacheng Wen,Weiwei Diao,Ying Zhou,Ruixin Li,Dayang Xu,Weijia Xie,Liang Wu
Simple SummaryHepatocellular carcinoma (HCC) is characterized by high incidence and mortality rates, yet effective therapeutic drugs remain scarce, creating an urgent need for viable treatment strategies. This study aimed to develop novel small-molecule anti-HCC agents based on the naturally derived antitumor compound caffeic acid phenethyl ester (CAPE), evaluate their efficacy against HCC, and investigate their underlying pharmacological mechanisms. A total of 28 structurally analogous small-molecule derivatives were synthesized, from which the most potent compound, designated WX006, was selected. Using an integrated approach encompassing molecular biology, cell biology, computational biology, and multi-omics analysis, we demonstrated that WX006 effectively depletes Nicotinamide adenine dinucleotide (NAD+) in HCC cells by binding to NADH: Ubiquinone Oxidoreductase Core Subunit S2 (NDUFS2), thereby disrupting mitochondrial function and intracellular metal ion homeostasis. This study provides valuable and independent insights into the development of derivatives based on the natural small molecule CAPE and establishes a further foundation for the advancement of anti-HCC therapies.Background: In this study, 28 caffeic acid phenethyl ester (CAPE) derivatives were designed and synthesized, and their anti-proliferative activities were evaluated against two representative human hepatocellular carcinoma (HCC) cell lines. The half-maximal inhibitory concentration (IC50) was used as the activity metric. Among these derivatives, compound WX006 displayed the most potent anti-proliferative effect, with IC50values of 3.332 μM and 3.764 μM after 48 h of treatment, significantly lower than those of the parent compound CAPE. Consequently, WX006 was selected for further investigation into its antitumor efficacy and underlying mechanisms. Methods: To investigate the pharmacological mechanism of WX006, we employed a combination of high-throughput transcriptomics, metabolomics, and mitochondrial function analysis to elucidate its intracellular mechanisms of action. Results: WX006 disrupts cytoplasmic-mitochondrial metal ion homeostasis, triggering ferroptosis and cuproptosis through iron-copper dysregulation. Computational modeling revealed that WX006 selectively inhibits mitochondrial NDUFS2 subunit of respiratory chain complex I, which may induce NAD+exhaustion and consequent energy metabolism collapse in tumor cells. These “metabolism & metal homeostasis” dual mechanisms collectively underpin its robust anti-tumor effects. Therapeutic efficacy of WX006 was further validated in murine H22 ectopic xenograft and Hepa1-6-Luc orthotopic xenograft models, where WX006 exhibited superior tumor suppression compared to sorafenib, alongside favorable safety profiles. Conclusions: Our findings establish a foundational rationale for further pharmaceutical development of CAPE derivates as a promising therapeutic candidate for hepatocellular carcinoma.
研究领域:
肿瘤学
·
药物化学
·
分子生物学
·
癌症药理学
·
代谢组学
·
计算生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
STAR Protocols
·
2022
·
IF 0
Mei-Mei Li,Fan-En Kong,Guang-Meng Li,Yi-Ti He,Xiao-Feng Zhang,Cheng-Yang Zhang,Jie-Kai Liang,Xin-Yuan Guan,Ning-Fang Ma,Mao-Bin Xie,Ming Liu
Summary Here, we present a detailed protocol for the identification of potential oncofetal targets for hepatocellular carcinoma (HCC) patients through a hepatocyte differentiation model and a sorafenib refractory cell-line-derived xenograft model. We describe the procedures of tumor sphere formation, organoid generation, and subcutaneous tumor formation for functional studies. We then detail the procedures of immunohistochemistry and immunofluorescence for examination of changes in lineage-specific markers. Finally, we describe the development of antibody-based therapeutics targeting tumor lineage plasticity in HCC. For complete details on the use and execution of this protocol, please refer to Kong et al. (2021). 1
研究领域:
肿瘤学
·
分子生物学
·
癌症研究
·
细胞生物学
✓ 已验证
DOI
PubMed
Scientific Reports
·
2017
·Vol. 7
·期 1
·1-12
·
IF 4.259
Cai Chenlei,Xie Yuexia,Wu liangliang,Chen Xiaojing,Liu Hongmei,Zhou Yan,Zou Hanbing,Liu Dejun,Zhao Yanan,Kong Xianming,Liu Peifeng
Hepatic carcinoma (HCC) is a lethal disease associated with high morbidity and poor prognosis. Recently years, gene therapies have offered novel modalities to improve the prognosis of HCC patients. MicroRNA-99a (miR-99a) is frequently down-regulated in HCC, where it acts as a tumor suppressor. Therefore, we constructed monomethoxy (polyethylene glycol)-poly(D,L-lactide- co -glycolide)-poly(L-lysine)-lactobionic acid- anti-vascular endothelial growth factor antibody (mPEG-PLGA-PLL-LA/VEGFab or PEAL-LA/VEGFab) nanoparticles (NPs) with highly specific targeting properties as carriers to restore the expression of miR-99a both in vitro and in vivo , to inhibit HCC progression. In vitro , PEAL-LA/VEGFab NPs showed more efficient delivery of miR-99a to HepG2 cells than the conventional transfection reagent Lipofectamine TM 2000 (Lip2000). The higher delivery efficiency associated with PEAL-LA/VEGFab NPs consequently resulted in down-regulation of target genes and suppression of the proliferation, migration and invasion of HepG2 cells. In vivo , miR-99a-PEAL-LA/VEGFab NPs inhibited tumor xenograft growth in HCC-bearing mice without causing obvious systemic toxicity. Our results demonstrate that PEAL-LA/VEGFab NPs selectively and effectively deliver miR-99a to HCC cells based on the double-targeting character of these nanoparticles, thereby offering potential for translation into effective clinical therapies for HCC.
研究领域:
癌症研究
·
分子生物学
·
药学
·
纳米技术
✓ 已验证
产品关联
DOI
PubMed
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
·
2025
·
IF 5.6
Qi Liu,Ziwei Liang,Jiapu Wang,Yuhui Wang,Jie Wang,Shaojie Wang,Zhi Du,Liqin Zhao,Yan Wei,Di Huang
Hepatocellular carcinoma (HCC) is a leading cause of cancer-related deaths worldwide, with conventional treatments often accompanied by severe side effects. Recently, nanozymes have been extensively employed in cancer therapy due to their enhanced enzymatic activities, stability compared to native enzymes. However, a standalone nanozyme exhibits insufficient targeting capability and fails to specifically localize to the pathological site. In this study, we successfully synthesized a multifunctional iron-based-nanozyme delivery system - Fe 3 O 4 -OA-DHCA-PEI-MAN@DSF modified with PEI and MAN by the thermal decomposition method. This mannose-modified nanozyme can specifically target HCC cells via an external magnetic field and mannose-mannose receptor (MRC2) binding. In addition, it exhibits good biocompatibility and pH-dependent drug release characteristics. Within the acidic tumor microenvironment, the iron-based nanozyme initiates intracellular fenton reactions, boosting reactive oxygen species (ROS) production, which ultimately induces apoptosis in HCC cells. Concurrently, the disulfiram small molecule released from the Fe 3 O 4 -OA-DHCA-PEI-MAN@DSF nanozyme binds to the FROUNT factor within monocyte-macrophages, thereby inhibiting their response to chemotactic signals emitted by liver cancer cells. This process ultimately suppresses the recruitment of macrophages by HCC cells, reshaping the tumor microenvironment and supporting effective liver cancer treatment. Moreover, this nanozyme system holds potential for MRI-guided targeted chemotherapy combined with chemodynamic therapy, aiming to refine the early diagnosis and precision treatment of hepatic carcinoma, and paving the way for the creation of sophisticated integrated nanoplatforms melding diagnostic and therapeutic functionalities.
研究领域:
癌症研究
·
纳米技术
·
生物医学工程
·
药学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
·
2022
·
IF 3.571
Huan Wu,Hui Cheng,Shengyong Luo,Can Peng,An Zhou,Zhiwu Chen,Hong Wu,Qinglin Li
Huachansu (HCS) injection has been used for the clinical treatment of hepatocellular carcinoma (HCC) patients in China for more than thirty years. However, the underlying mechanisms of HCS injection in inhibiting HCC remains unclear. In this study, we aimed to evaluate the effects of HCS injection on HCC both in vitro and in vivo and to systematically explore the underlying mechanisms of HCS’s actions against HCC using an ultrahigh-performance liquid chromatography-high resolution mass spectrometry (UPLC-HRMS)-based cellular metabolomics and lipidomics approach. MTT and DAPI staining were performed to evaluate the effects of HCS injection on cell proliferation and apoptosis , respectively, in human HepG2 HCC cells with and without HCS treatment. An H22 hepatoma-bearing mouse model was employed to investigate the anti-HCC action of HCS injection in vivo. A UPLC-HRMS-based cellular metabolomics and lipidomics method was employed to characterize cellular metabolite fingerprinting, to identify potential biomarkers associated with the effect of HCS injection on the inhibition of HCC and to explore the anti-HCC mechanisms of HCS injection from the perspective of cellular metabolism. As a result, HCS injection inhibited the proliferation of HepG2 cells and induced their apoptosis. Body weight loss, sarcoma weights and volumes of H22 hepatoma-bearing mice in the HCS treatment group were significantly attenuated compared to those in the model group. Twenty-five biomarkers responsible for the intervention effect of HCS were screened and annotated using UPLC-HRMS-based cellular metabolomics and lipidomics. Among these biomarkers, two cellular metabolites, uridine diphosphate- N -acetylglucosamine (UDP-GlcNAc) and glutathione , were confirmed unambiguously using the reference substances. Metabolic pathway analysis revealed that the anti-HCC effects of HCS injection primarily involved the metabolism of glutathione, cysteine and methionine , sphingolipid , fatty acid biosynthesis, amino sugar and nucleotide sugars . As evidenced by western blotting experiments, the changes in UDP-GlcNAc content in response to HCS injection were linked to the inhibition of UDP-GlcNAc pyrophosphorylase 1 (UAP1) expression in HepG2 cells. In conclusion, HCS injection has a curative anti-HCC effect, and a UPLC-HRMS-based cellular metabolomics and lipidomics approach combined with further confirmatory experiments is a promising means of discovering its underlying mechanisms.
研究领域:
肿瘤学
·
药理学
·
代谢组学
·
脂质组学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ARCHIV DER PHARMAZIE
·
2024
·
IF 4.3
Jiahong Su,Xingyue Wang,Sha Li,Xu Wu,Mingxing Li,Fukuan Du,Shuai Deng,Jing Shen,Yueshui Zhao,Zhangang Xiao,Yu Chen
Glycyrrhetinic acid (GA) is a naturally occurring triterpene compound. The aim of this study was to employ the pharmacophore hybrid strategy to merge GA with various dithiocarbamates and obtain novel compounds with better antitumor activities. We present a two-step synthetic protocol wherein the GA derivative underwent reaction with carbon disulfide and various secondary amines in a one-pot manner under mild conditions, facilitating the preparation of a series of structurally novel GA-dithiocarbamate derivatives. Bioassay screening revealed that the representative compound 3c demonstrated the capacity to reduce the mitochondrial membrane potential in Hep3B and Huh-7 cells, induce nuclear apoptosis, inhibit invasion and migration, and prompt both early and late apoptosis. Furthermore, our research findings indicated that this apoptotic phenomenon may be associated with the expression of Bcl-2, Bax, Bak, PARP, and cleaved-PARP proteins. Utilizing network pharmacology for predicting core targets and signaling pathways of compound 3c for hepatocellular carcinoma (HCC) treatment involved employing molecular docking models to demonstrate high affinity between compound and target protein. In conjunction with Western blot analysis, compound 3c may impact HCC through the PI3K-AKT-mTOR pathway.
研究领域:
药理学
·
肿瘤学
·
药物化学
·
细胞生物学
✓ 已验证
DOI
PubMed
高影响因子
SENSORS AND ACTUATORS B-CHEMICAL
·
2023
·
IF 8.4
Xixiang Xie,Xiyu Liu,Wenxi Lu,Tao Wu,Jian He,Zhiming Deng,Faquan Lin,Pan Wu,Bing Wang,Yong Huang
N 6 -methyladenosine (m 6 A) modification has an impact on RNA metabolism, and it has been demonstrated that m 6 A regulatory mechanisms play an important role in tumorigenesis and may serve as a potential hepatocellular carcinoma (HCC) marker. We constructed a dual-signal amplification strategy electrochemical biosensor based on biocatalytic silver deposition and hybridization chain reaction (HCR). Enzymatic silver deposition was performed on the electrode and detected by linear sweep voltammetry (LSV), which was used for the quantitative detection of m 6 A. There was a nice linear relationship between the current response values and the logarithm of the m 6 A RNA concentration in the range of 0.5 pM-5 μM, with a detection limit as low as 25 fM. The concentration of m 6 A detected by the sensor constructed in this work is consistent with the results obtained using commercial colorimetric immunoassays . What's more, the analysis of m 6 A RNA in the serum of HCC patients using the developed sensor showed the high analytical efficiency of the designed strategy, which was superior to three other markers (AFP, CEA, CA199). The constructed electrochemical biosensor has good sensitivity, specificity and reproducibility for the detection of m 6 A RNA, and the sensing platform has promising clinical applications in the diagnosis and prognosis of HCC.
研究领域:
癌症生物学
·
分子生物学
·
电化学
·
生物技术
·
临床诊断
✓ 已验证
产品关联
DOI
高影响因子
Biomed Research International
·
2022
·
IF 3.246
Xiaomeng Zou,Tiantian Li,Yingxuan Mao,Mingwei Zhu,Xi Chen,Jiamei Niu,Tianxiu Dong,Jian Jiang,Xiuhua Yang
Objectives . Preparation of a multifunctional drug-loaded phase-change nanoparticle (NP), pirfenidone perfluoropentane liposome NPs (PPL NPs), and combined with low-intensity focused ultrasound (LIFU) to influence epithelial mesenchymal transition (EMT) for hepatocellular carcinoma (HCC) by inhibiting the activity of activated Hepatic Stellate Cells (a-HSCs ). Methods . PPL NPs were prepared by the thin film dispersion method. The appearance, particle size, zeta potential, encapsulation efficiency, drug loading rate, drug release in vitro, and stability of PPL NPs were tested. The role of a-HSCs in HCC metastasis was studied by CCK-8, colony formation assay, apoptosis, cellular uptake assay, wound healing assay, and Transwell assay. Western blot was used to detect the related protein expression levels. In vitro and vivo, the acoustic droplet vaporization (ADV) of PPL NPs was tested at different times and LIFU intensities. Biosafety of the PPL NPs was assessed by measuring nude mouse body weight and hematoxylin and eosin (H&E) staining . Results. The results showed that the PPL NPs had good biosafety, with an average particle size of 346.6 ± 62.21 nm and an average zeta potential of -15.23 mV. When the LIFU power is 2.4 W/cm 2 , it can improve the permeability of cells, further promote the uptake of drugs by cells, and improve the toxicity of drugs. In vitro experiments showed that PPL NPs could inhibit the proliferation of a-HSCs cells, thereby affecting the metastasis of HCC, and were related to the TGF β -Smad2/3-Snail signaling pathway. Both in vivo and in vitro PPL NPs enhanced ultrasound imaging by LIFU-triggered ADV . Conclusion. The PPL NPs designed and prepared in this study combined with LIFU irradiation could significantly alter the EMT of HCC by inhibiting LX2. Clinically, PPL NPs will also be considered a promising contrast agent due to their ultrasound imaging capabilities.
研究领域:
纳米技术
·
肿瘤学
·
药剂学
·
超声成像
·
细胞生物学
✓ 已验证
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）