Tumor-associated macrophages (TAMs) are major components of the tumor microenvironment (TME) which are closely associated with the tumor malignant progression. However, the regulatory mechanisms by which TAMs influence the progression of triple-negative breast cancer (TNBC) remain unclear. Here, we report that hepatic leukemia factor (HLF) acts as a novel oncoprotein in TNBC. We found that HLF was regulated by transforming growth factor-beta1 (TGF-β1) that is secreted by TAMs. Then, HLF transactivated gamma-glutamyltransferase 1 (GGT1) to promote the ferroptosis resistance, thus driving TNBC cell proliferation, metastasis and cisplatin resistance. Reciprocally, IL-6 produced by TNBC cells activated the JAK2/STAT3 axis to induce TGF-β1 secretion by TAMs, thus constituted a feed-forward circuit. The accuracy of TNBC patient prognosis could be improved by employing a combination of HLF and GGT1 values. Thus, our findings document that the interactive dialogue between TNBC cells and TAMs promotes sustained activation of HLF in tumor cells through the IL-6-TGF-β1 axis. Subsequently, HLF promotes the ferroptosis resistance in TNBC cells via GGT1 and ultimately facilitates the malignant tumor progression. Our study provides a potential target for the treatment of TNBC.

The problem of antimicrobial resistance (AMR) has caused global concern due to its great threat to human health. Evidences are emerging for a critical role of biofilms, one of the natural protective mechanisms developed by bacteria during growth, in resisting commonly used clinical antibiotics. Advances in nanomedicines with tunable physicochemical properties and unique anti-biofilm mechanisms provide opportunities for solving AMR risks more effectively. In this review, we summarize the five "A" stages (adhesion, amplification, alienation, aging and allocation) of biofilm formation and mechanisms through which they protect the internal bacteria. Aimed at the characteristics of biofilms, we emphasize the design "THAT" principles (targeting, hacking, adhering and transport) of nanomedicines in their interactions with biofilms and internal bacteria. Furthermore, recent progresses in multimodal antibacterial nanomedicines, including biofilms disruption and bactericidal activity, and the types of currently available antibiofilm nanomedicines contained organic and inorganic nanomedicines are outlined and highlighted their potential applications in the development of preclinical research. Last but not least, we offer a perspective for the effectiveness of nanomedicines designed to address AMR and challenges associated with their clinical translation.

Background: Increasing researches have demonstrated the critical functions of MicroRNAs (miRNAs) in the progression of malignant tumors, including ovarian cancer. It was reported that miR-552 was an important oncogene in both breast cancer and colorectal cancer. However, the role of miR-552 in ovarian cancer (OC) remains to be elucidated. Methods: RT-PCR and western blot analysis were used to detect the expression of miR-552 and PTEN. The impact of miR-552 on ovarian cancer proliferation and metastasis was investigated in vitro. The prognostic value of miR-552 was evaluated using the online bioinformatics tool Kaplan-Meier plotter. Results: In the present study, we for first found that miR-552 was upregulated in ovarian cancer, especially in metastatic and recurrence ovarian cancer. Forced miR-552 expression promotes the growth and metastasis of ovarian cancer cells. Consistently, miR-552 interference inhibits the proliferation and metastasis of ovarian cancer cells. Mechanically, bioinformatics and luciferase reporter analysis identified Phosphatase and tension homolog (PTEN) as a direct target of miR-552. miR-552 downregulated the PTEN mRNA and protein expression in ovarian cancer cells. Furthermore, the PTEN siRNA abolishes the discrepancy of growth and metastasis capacity between miR-552 mimic ovarian cells and control cells. More importantly, upregulation of miR-552 predicts the poor prognosis of ovarian cancer patients. Conclusion: Our findings revealed that miR-552 could promote ovarian cancer cells progression by targeting PTEN signaling and might therefore be useful to predict patient prognosis.

Recurrence and chemoresistance of liver cancer has been attributed to the existence of liver tumor-initiating cells (T-ICs). It is important to decipher the molecular mechanism for acquisition of drug resistance and to design combinatorial therapeutic strategies. Cyclin G1 has been shown to play a pivotal role in initiation and metastasis of hepatocellular carcinoma. In this study, we found that enhanced cyclin G1 expression was associated with drug resistance of hepatoma cells and higher recurrence rate in hepatocellular carcinoma patients. Expression of cyclin G1 was elevated in liver T-ICs and closely correlated with the expression of liver T-IC markers. Forced cyclin G1 expression remarkably enhanced self-renewal and tumorigenicity of hepatoma cells. Cyclin G1 overexpression dramatically upregulated the expression of Sox2 both in vitro and in vivo, which was impaired by chemical inhibitors of Akt/mTOR signaling. Furthermore, blockade of Akt/mTOR signaling or interference of Sox2 expression suppressed cyclin G1–enhanced self-renewal, chemoresistance, and tumorigenicity of hepatoma cells, indicating that cyclin G1 expands liver T-ICs through Sox2 induction via Akt/mTOR signaling pathway. These results suggest that cyclin G1–induced liver T-IC expansion contributes to the recurrence and chemoresistance of hepatoma, and cyclin G1 may be a promising biomarker for individualized therapy of hepatocellular carcinoma patients. Mol Cancer Ther; 12(9); 1796–804. ©2013 AACR.

Background and Objectives: Immunotherapy has become the standard treatment for hepatocellular carcinoma (HCC), but it carries a risk of immune-related adverse events (irAEs) that can be life-threatening. This study employs bibliometric analysis to understand global scientific research on irAEs in cancer, focusing on characteristics and areas of interest. Additionally, a meta-analysis provides a comprehensive overview of irAEs in HCC patients receiving immune checkpoint inhibitor (ICI)-based therapies. Methods: We conducted a thorough search of Web of Science Core Collection (WoSCC) publications from 1999 to 2022. R and VOSviewer software were used for analysis. A meta-analysis was performed using data from PubMed, Embase, and the Cochrane Library databases up to March 22, 2022. Trials with HCC patients reporting irAE incidence were included. Quality assessment followed Cochrane risk of bias, Newcastle-Ottawa Scale (NOS), and Methodological Index for Non-Randomized Studies (MINORS). We used random-effects or fixed-effects models based on I2 values. Primary outcomes included any-grade irAEs and grade >= 3 irAEs. This review and meta-analysis are registered in PROSPERO as CRD42022318885. Results: In bibliometric analysis, we included 2946 papers, showing a consistent rise in annual publications on irAEs in cancer research. Frequent keywords were "nivolumab", "immune checkpoint inhibitor", and "immune-related adverse event". "Hepatocellular carcinoma" emerged as a prominent research focus linked to irAEs. We conducted a comprehensive meta-analysis on irAE incidence in HCC patients, including 29 studies. The overall incidence of any-grade irAEs was 61.0% (95% CI 38.5%-81.3%), and grade >= 3 irAEs was 13.2% (95% CI 7.9%-19.6%). Treatment-related mortality occurred in 3.1% (95% CI 0.8%-6.3%), with treatment discontinuation at 10.7% (95% CI 6.3%-16.0%). Reactive cutaneous capillary endothelial proliferation (RCCEP) was the most common any-grade irAE, while elevated aspartate aminotransferase (AST) was the most common grade >= 3 irAE. Treatment strategies were independently associated with specific irAEs, as indicated by multivariable analysis. Conclusion: This study provides valuable insights into the current research landscape of irAEs in cancer and ofers a comprehensive overview of irAEs in HCC patients undergoing ICI-based therapy. The relatively high incidence of irAEs and their association with treatment strategies emphasize the need for careful management by clinicians when treating HCC patients. These findings offer significant guidance for optimizing care and treatment for HCC patients.