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Background: Hepatocellular carcinoma (HCC) is the most common primary liver cancer worldwide. Multiple observational studies demonstrated a negative association between the use of antithrombotic agents and the risk of HCC. However, the precise causal relationship between these factors remains uncertain. Therefore, our study used a two-sample Mendelian randomization (MR) analysis to assess the causal link between these two factors., Method: The summary statistics of single nucleotide polymorphisms (SNPs) associated with the use of antithrombotic agents were acquired from a genome-wide association study (GWAS) performed on individuals of European descent. A two-sample MR analysis was performed using the inverse variance weighting (IVW), the weighted median estimate, the MR-Egger regression, and the weighted-mode estimate. Sensitivity analysis of the primary findings was performed using MR-PRESSO, MR-Egger regression, Cochran's Q test, and Leave-one-out analysis., Results: Ten SNPs associated with the use of antithrombotic agents were selected as instrumental variables. The MR analysis performed using the four methods mentioned above revealed a negative causal association between the use of antithrombotic agents and HCC. Univariate MR estimates based on the inverse variance weighting (IVW) method suggested a negative causal association between the use of antithrombotic agents and HCC [odds ratio (OR) 0.444, 95% confidence interval (CI) 0.279 to 0.707, P = 0.001]. The other methods also produced similar results. No heterogeneity and horizontal pleiotropy were found., Conclusion: Our findings suggested an inverse causal association of antithrombotic agents with the risk of HCC., (© 2024. The Author(s).)

Purpose: The efficacy of systemic therapy for hepatocellular carcinoma (HCC) is limited mainly by the complex tumor defense mechanism and the severe toxic side-effects of drugs. The efficacy of apatinib (Apa), a key liver cancer treatment, is unsatisfactory due to inadequate targeting and is accompanied by notable side-effects. Leveraging nanomaterials to enhance its targeting represents a crucial strategy for improving the effectiveness of liver cancer therapy., Patients and Methods: A metal polyphenol network-coated apatinib-loaded metal-organic framework-based multifunctional drug-delivery system (MIL-100@Apa@MPN) was prepared by using metal-organic frameworks (MOFs) as carriers. The nanoparticles (NPs) were subsequently characterized using techniques such as X-ray diffraction (XRD), transmission electron microscopy (TEM), zeta potential measurements, and particle size analysis. In vitro experiments were conducted to observe the drug release kinetics and cytotoxic effects of MIL-100@Apa@MPN on HepG2 cells. The in vivo anti-tumor efficacy of MIL-100@Apa@MPN was evaluated using the H22 tumor-bearing mouse model., Results: The formulated MIL-100@Apa@MPN demonstrates remarkable thermal stability and possesses a uniform structure, with measured drug-loading (DL) and encapsulation efficiency (EE) rates of 28.33% and 85.01%, respectively. In vitro studies demonstrated that HepG2 cells efficiently uptake coumarin-6-loaded NPs, and a significant increase in cumulative drug release was observed under lower pH conditions (pH 5.0), leading to the release of approximately 73.72% of Apa. In HepG2 cells, MIL-100@Apa@MPN exhibited more significant antiproliferative activity compared to free Apa. In vivo, MIL-100@Apa@MPN significantly inhibited tumor growth, attenuated side-effects, and enhanced therapeutic effects in H22 tumor-bearing mice compared to other groups., Conclusion: We have successfully constructed a MOF delivery system with excellent safety, sustained-release capability, pH-targeting, and improved anti-tumor efficacy, highlighting its potential as a therapeutic approach for the treatment of HCC., Competing Interests: The authors have no relevant financial or non-financial interests to disclose., (© 2024 Yang et al.)

Background: The efficacy of systemic chemotherapy for hepatocellular carcinoma (HCC) is predominantly hampered by low accumulation in tumor tissue and the high systemic toxicity of anticancer drugs. In this study, we designed an in situ drug-loaded injectable thermosensitive hydrogel system for the simultaneous delivery of norcantharidin-loaded nanoparticles (NCTD-NPs) and doxorubicin (Dox) via intratumoral administration to HCC tumors., Methods: NCTD-NPs were prepared by the thin film dispersion method using PCEC polymers as the carrier. Then, NCTD-NPs and Dox were co-encapsulated in a thermosensitive hydrogel based on Pluronic F127 (PF127) to construct a dual drug-loaded hydrogel system. The rheological properties of the drug-loaded hydrogel were studied using a rheometer. Drug release of the drug-loaded hydrogel and cytotoxicity in HepG2 cells were evaluated in vitro. An H22 tumor-bearing mice model was used to assess the in vivo antitumor activity of the drug-loaded hydrogel via intratumoral administration., Results: The prepared drug-loaded hydrogel exhibited good thermal-sensitive properties, which remained liquid at room temperature and rapidly transformed into a non-flowing gel at body temperature, and released the drugs in a sustained manner. In vitro studies revealed that the drug-loaded hydrogel exhibited remarkable antiproliferative activity in HepG2 cells compared to free drugs. In vivo antitumor efficacy experiments showed that the drug-loaded hydrogel significantly suppressed tumor growth, alleviated side effects, and prolonged the survival time of mice bearing H22 tumors compared to the other groups. Moreover, immunohistochemical staining revealed that the expression of Ki-67 and CD31 in the drug-loaded hydrogel group was significantly lower than that in the other groups (P < 0.05), indicating that the drug-loaded hydrogel effectively inhibited tumor proliferation and angiogenesis., Conclusion: The formulated hybrid thermosensitive hydrogel system with sustained drug release and enhanced therapeutic efficacy was demonstrated to be a promising strategy for the local-regional treatment of HCC via intratumoral administration., Competing Interests: The authors declare that they have no conflicts of interest related to this work., (© 2021 Gao et al.)