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As other malignancies, statistical cure can occur for HCC, primarily with LT and secondarily with HR, depending on waiting-list capabilities and efficacy of tumor recurrence therapies after resection.

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Hepatocellular carcinoma (HCC) is one of the most common and deadly gastrointestinal malignancies. Given its insensitivity to traditional systematic chemotherapy, new therapeutic strategies for efficient HCCs treatment are urgently needed. Here, the development of a novel 2D MXene-based composite nanoplatform for highly efficient and synergistic chemotherapy and photothermal hyperthermia against HCC is reported. A surface-nanopore engineering strategy is developed for the MXenes' surface functionalization, which achieves the uniform coating of a thin mesoporous-silica layer onto the surface of 2D Ti C MXene (Ti C @mMSNs). This strategy endows MXenes with well-defined mesopores for on-demand drug release/delivery, enhanced hydrophilicity/dispersity, and abundant surface chemistry for targeting engineering. Systematic in vitro and in vivo evaluations have demonstrated the high active-targeting capability of arginine-glycine-aspartic acid (RGD)-targeting Ti C @mMSNs into tumor, and the synergistic chemotherapy (contributed by the mesoporous shell) and photothermal hyperthermia (contributed by the Ti C MXene core) completely eradicate the tumor without obvious reoccurrence. This work not only provides a novel strategy for efficiently combating HCC by developing MXene-based composite nanoplatforms, but also paves a new way for extending the biomedical applications of MXenes by surface-nanopore engineering.

Hepatocellular carcinoma (HCC) is one of the deadliest malignancies worldwide featured with the poor prognosis and high mortality in affected patients. Given its insensitivity to conventional systemic chemotherapy, the development of novel modalities for HCC management is highly urgent. Sonodynamic therapy (SDT) has gained considerable momentum in cancer therapy. Especially, through synergistic SDT/chemotherapy, SDT would enhance the chemotherapeutic process on inhibiting tumor growth, which holds great potential on combating HCC. In this work, we report on the design/fabrication of targeted biodegradable nanosonosensitizers based on hollow mesoporous organosilica nanoparticles (HMONs), followed by pore-engineering including covalent anchoring of protoporphyrin (PpIX, HMONs-PpIX) and conjugation of arginine-glycine-aspartic acid in order to specifically targeting HCC cells. Such nanosonosensitizers provide efficient loading and controllable stimuli-responsive release of chemotherapeutic agents for HCC-targeting chemotherapy, thus promoting an enhancing chemotherapeutic process via the unique sonotoxicity under ultrasound irradiation. The HMONs matrix with biologically active organic groups in the framework (disulfide bond) are endowed with intrinsic tumor microenvironment-responsive biodegradability and improved biocompatibility/ biosafety. In particular, a synergistic inhibition effect of drug-loaded HMONs-PpIX-arginine-glycine-aspartic acid on HCC growth has been systematically demonstrated both in vitro and in vivo (84.7% inhibition rate), which brings insights and meets the versatile therapeutic requirements for HCC management. Scheme 1. Schematic illustration of the synthetic process of HMONs-PpIX-RGD and synergistic chemo-SDT against HCC tumor xenograft on nude mice. a) Schematic diagram of synthesizing HMONs and further pore engineering with PpIX. b) Schematic process of surface PEG modification, RGD conjugation, and DOX loading on as-synthesized HMONs. c) Schematic illustration of multitherapeutic functions of HMONs-PpIX-RGD, including free transport within blood vessel after intravenous injection, specific recognition between RGD and ligands expressed on HCC cell membranes, GSH/ US-responsive drug release, and enhanced/synergistic chemo-SDT process.www.afm-journal.de www.advancedsciencenews.com 1800145 (3 of 16)

Background/Aims: TGF-β plays a key role in the progression of various tumors. The main objective of our study was to investigate whether TGF-β is able to regulate N-nitrosodiethylamine (DEN)-induced hepatocellular carcinoma (HCC) progression in a mouse model by inducing Treg cell polarization. Methods: HCC progression, TGF-β and Foxp3 expression levels, serum TGF-β, IL10 and GP73 levels as well as percentage of Treg cells were analyzed in healthy, HCC and HCC+SM-16 mouse groups. The effect of TGF-β on Treg cell polarization in vitro was measured by flow cytometric analysis. The expression of TGF-β and IL10 was identified by IHC in HCC patients and the correlation between TGF-β and IL10 was also assessed. Results: TGF-β expression is up-regulated in a DEN-induced HCC mouse model. TGF-β can promote the differentiation of Foxp3⁺CD4⁺ T cells (Treg cells) in vitro. However, blocking the TGF-β pathway with a specific TGF-β receptor inhibitor, SM-16, reduced HCC progression and the percentage of Treg cells in liver tissue. The correlation between TGF-β and Treg cells was also confirmed in HCC patients and the expression of both TGF-β and IL-10 was shown to be associated with HCC progression. Conclusion: TGF-β is necessary for HCC progression, acting by inducing Treg cell polarization.

Spontaneous rupture predicted poor long-term survival after hepatectomy for HCC, but surgical treatment seems possible, safe and appropriate in selected patients.

A high preoperative HBV DNA level was an independent risk factor of MVI. Antiviral treatment administered more than 90 days before surgery was associated with reduced incidences of MVI and early tumor recurrence after partial hepatectomy for HBV-related HCC.