Globally, liver cancer, which is one of the major cancers worldwide, has attracted the growing attention of technological researchers for its high mortality and limited treatment options. Hydrogels ...are soft 3D network materials containing a large number of hydrophilic monomers. By adding moieties such as nitrobenzyl groups to the network structure of a cross‐linked nanocomposite hydrogel, the click reaction improves drug‐release efficiency in vivo, which improves the survival rate and prolongs the survival time of liver cancer patients. The application of a nanocomposite hydrogel drug delivery system can not only enrich the drug concentration at the tumor site for a long time but also effectively prevents the distant metastasis of residual tumor cells. At present, a large number of researches have been working toward the construction of responsive nanocomposite hydrogel drug delivery systems, but there are few comprehensive articles to systematically summarize these discoveries. Here, this systematic review summarizes the synthesis methods and related applications of nanocomposite responsive hydrogels with actions to external or internal physiological stimuli. With different physical or chemical stimuli, the structural unit rearrangement and the controlled release of drugs can be used for responsive drug delivery in different states.
Cross‐linked hydrophilic polymer chains that can form gels are widely utilized for biomedical applications, such as drug delivery. Various studies have also demonstrated the effects of particle size and surface morphology on drug release from particles in liver cancer therapy. Mechanistic understandings of responsive hydrogels in responsive stimuli are provided, by which better clinical choices may be approached.
Background
Survival after liver resection of hepatocellular carcinoma (HCC) remains poor because of a high incidence of recurrence. We sought to investigate risk factors, patterns, and long‐term ...prognosis among patients with early and late recurrence after liver resection for hepatitis B virus (HBV)–associated HCC.
Methods
Data of consecutive patients undergoing curative resection for HBV‐associated HCC were analyzed. According to the time to recurrence after surgery, recurrence was divided into early (≤2 years) and late recurrence (>2 years). Characteristics, patterns of initial recurrence, and postrecurrence survival (PRS) were compared between patients with early and late recurrence. Risk factors of early and late recurrence and predictors of PRS were identified by univariable and multivariable Cox regression analyses.
Results
Among 894 patients, 322 (36.0%) and 282 (31.5%) developed early and late recurrence, respectively. On multivariable analyses, preoperative HBV‐DNA >104 copies/mL was associated with both early and late recurrence, whereas postoperative no/irregular antiviral therapy was associated with late recurrence. Compared with patients with late recurrence, patients with early recurrence had a lower proportion of intrahepatic‐only recurrence (72.0% vs. 91.1%, p < .001), as well as a lower chance of receiving potentially curative treatments for recurrence (33.9% vs. 50.7%, p < .001) and a worse median PRS (19.1 vs. 37.5 months, p < .001). Multivariable analysis demonstrated that early recurrence was independently associated with worse PRS (hazard ratio, 1.361; 95% confidence interval, 1.094–1.692; p = .006).
Conclusion
Although risk factors associated with early recurrence and late recurrence were different, a high preoperative HBV‐DNA load was an independent hepatitis‐related risk for both early and late recurrence. Early recurrence was associated with worse postrecurrence survival among patients with recurrence.
Implications for Practice
Liver resection is the main curative treatment for hepatocellular carcinoma (HCC), but postoperative survival remains poor because of high recurrence rates. This study investigated the risk factors and patterns of early and late recurrence and found that a high preoperative hepatitis B virus (HBV) DNA load was an independent hepatitis‐related risk factor for both. Early recurrence was also independently associated with worse postrecurrence survival. These data may provide insights into different biological origin and behavior of early versus late recurrence after resection for HBV‐associated HCC, which could be helpful to make individualized treatment decision for recurrent HCC, as well as strategies for surveillance recurrence after resection.
Worldwide, hepatitis B virus (HBV) infection is the main etiology of hepatocellular carcinoma (HCC). This article defines risk factors and patterns of recurrence after curative resection of HBV‐associated HCC, aiming to provide evidence for appropriate selection of treatment options for recurrent HCC.
Hepatocellular carcinoma (HCC) is one of the most fatal malignancies with few effective treatment options all around the world. The efficacy of the arisen immune checkpoint therapy is still uncertain ...due to local immunosuppression. In order to further overcome T cell suppression in the tumor immune microenvironment while promoting the immune response of antigen‐presenting cells, a biointerfacing antagonizing T‐cell inhibitory nanoparticles (BAT NPs) has been developed by cloaking platelet membrane on the PLGA microsphere surface to load T‐cell immunoglobulin domain and mucin domain‐3 antibodies (anti‐TIM‐3) as well as PD‐L1. Notably, in addition to activating the proliferation and migration of T cells, the contained anti‐TIM‐3 can cooperate with PD‐L1 checkpoint blockade to exert therapeutic effects. Furthermore, the components of BAT NPs like anti‐TIM‐3 and platelet can act together for collagen deposition in tumor starvation treatment. Thus, a novel targeting therapeutic strategy that can effectively reverse the immune‐inhibiting microenvironment is effectively applied to PD‐L1 checkpoint combination therapy. Such therapeutic effect can subsequently activate the effector T lymphocytes and antigen presentation of dendritic cells as well as the polarization of M1‐type macrophages. Last, the study presented the synergistic effect of immune therapeutic adjuvants and BAT NPs components in achieving tumor inhibition and prolonging tumor‐burden survival.
The biointerfacing antagonizing T‐cell Inhibitory nanoparticles (BAT NPs) are synthesized to participate in Hepatocellular carcinoma immunoregulatory therapy and tumor starvation therapy. The platelet membrane acts as a bionic and targeted function. BAT NPs can be combined with PD‐L1 checkpoint therapy to activate T cells, promote dendritic cells proliferation and M1 polarization, and the following collagen deposition contributes to starvation therapy.
Hepatocellular carcinoma (HCC) is acknowledged as an immunosuppressive neoplasm, whereby the inactive microenvironment facilitates immune tolerance and evasion of HCC. Post‐surgical resected liver ...cancer exhibits a proclivity for relapse, rendering prevention of recurrence challenging as it may transpire at any point subsequent to surgery. Among the various anti‐recurrence interventions, the primary clinical approach involving the administration of regimens atezolizumab and bevacizumab (A+T) is deemed the most efficacious in reversing the tumor microenvironment, albeit still lacking in complete satisfaction. Therefore, the objective is to utilize a recently developed block copolymer as a protective carrier for two specific monoclonal antibody drugs. Subsequently, a modified hemostatic hydrogel will be synthesized for application during hepatic surgery. The immunotherapy impact of this approach is significantly prolonged and intensified due to the combined hemostasis properties and controlled release of the constituents within the synthesized nanocomposite hydrogel. Furthermore, these nanocomposite hydrogels exhibit remarkable efficacy in preventing postoperative wound bleeding and substantially enhancing the safety of liver cancer resection. This research on the anti‐recurrence hydrogel system presents a novel therapeutic approach for addressing local recurrence of liver cancer, potentially offering a substantial contribution to the field of surgical treatment for liver cancer in the future.
Among the various anti‐recurrence interventions, the primary clinical approach involving the administration of regimens atezolizumab and bevacizumab is deemed the most efficacious in reversing the tumor microenvironment, albeit still lacking in complete satisfaction. This research on the anti‐recurrence hydrogel system presents a novel therapeutic approach for addressing local recurrence of liver cancer, potentially offering a substantial contribution to the field of surgical treatment for liver cancer in the future.
Krüppel-like factor 8 (KLF8), a cancer-promoting factor that regulates critical gene transcription and cellular cancer-related events, has been implicated in tumor development and progression. ...However, the functional role of KLF8 in the pathogenesis of hepatocellular carcinoma (HCC) remains largely unknown.
The gene expression patterns and genome-wide regulatory profiles of HCC cells after KLF8 knockout were analyzed by using RNA sequencing (RNA-seq) and chromatin immunoprecipitation sequencing (ChIP-seq) of histone H3 lysine 27 acetylation (H3K27ac) combined with bioinformatics analysis. Transcription factor-binding motifs that recognized by KLF8 were evaluated by motif analysis. For the predicted target genes, transcriptional changes were examined by ChIP, and loss of function experiments were conducted by siRNA transfection.
KLF8 functioned as a transcription repressor in HCC and mainly regulated apoptotic-related genes directly. A total of 1,816 differentially expressed genes after KLF8 knockout were identified and significantly corresponded to global changes in H3K27ac status. Furthermore, two predicted target genes, high-mobility group AT-hook 2 (HMGA2) and matrix metalloproteinase 7 (MMP7), were identified as important participants in KLF8-mediated anti-apoptotic effect in HCC. Knockout of KLF8 enhanced cell apoptosis process and caused increase in the associated H3K27ac, whereas suppression HMGA2 or MMP7 attenuated these biological effects.
Our work suggests a novel role and mechanism for KLF8 in the regulation of cell apoptosis in HCC and facilitates the discovery of potential therapeutic targets for HCC treatment.
•Propensity score matching analysis in this study is wanted to balance the significant differences in enrollment.•More characteristics variables could be discussed in this study to increase the ...reliability and accuracy of the conclusion.•Due to irrational category of operations which may confuse the readers, more accurate category and elaboration are need.
Serum prealbumin is a sensitive and stable marker for nutritional status and liver function. Whether preoperative prealbumin level is associated with long-term prognosis in patients undergoing liver ...resection for hepatocellular carcinoma (HCC) is unclear.
Patients who underwent liver resection for HCC between 2001 and 2014 at six institutions were enrolled. These patients were divided into the low and normal prealbumin groups using a cut-off value of 170 mg/L for preoperative prealbumin level. The overall survival (OS) and recurrence-free survival (RFS) were compared between them.
In 1483 patients, 437 (29%) had a low prealbumin level. The 3- and 5-year OS and RFS rates of patients in the low-prealbumin group were 57 and 31%, and 40 and 20%, respectively, which were significantly poorer than those in the normal-prealbumin group (76 and 43%, and 56 and 28%, respectively, both p < 0.001). Multivariable Cox-regression analyses revealed that preoperative prealbumin level was an independent predictor of OS (HR, 1.45, 95% CI: 1.24–1.70, p <0.001) and RFS (HR, 1.28, 95% CI: 1.10–1.48, p <0.001).
Preoperative prealbumin level could be used in predicting long-term prognosis for patients undergoing liver resection for HCC.
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