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Objective: We developed and validated a clinical-radiomics model for preoperative prediction of the short-term efficacy of initial drug-eluting beads transarterial chemoembolization (D-TACE) treatment in patients with hepatocellular carcinoma (HCC). Methods: In this retrospective cohort study of 113 patients with intermediate and advanced HCC, 5343 features were extracted based on three sequences of the arterial phase (AP), diffusion-weighted imaging, and T2-weighted images based on contrast-enhanced magnetic resonance imaging, and minimum redundancy maximum correlation and least absolute shrinkage and selection operator (LASSO) regression were applied for feature selection and model construction. Multifactor logistic regression was used to build a clinical-imaging model based on clinical factors and a clinical-radiomics model. The area under the curve (AUC) and calibration curves were used to assess model performance, and the clinical value of the model was analyzed using decision curve analysis. The relationship between the actual and predicted short-term efficacy of the combined model and progression-free survival (PFS) was evaluated using Kaplan–Meier survival curves and log-rank tests. Results: A total of 34 radiomics features were selected by LASSO, and the clinical-radiomics model had the best predictive performance (AUC = 0.902 and AUC = 0.845 for the training and testing sets, respectively), and the model based on AP had the best predictive performance among the four radiomics models (AUC = 0.89 for the training set and AUC = 0.85 for the testing set); the multifactorial logistic regression results showed that microsphere type (p = 0.042) and AP Rad-score (p = 0.01) were associated with short-term efficacy. In addition, a difference in PFS was observed in patients with HCC with different short-term efficacies predicted by the combined model. Moreover, prognosis was better in the objective versus non-objective response group. Conclusions: The combined clinical-radiomics model is an effective predictor of the short-term efficacy of initial D-TACE in patients with HCC, contributing to clinical and economic benefits for patients. [ABSTRACT FROM AUTHOR]

Background: Triple-negative breast cancer is a complex breast malignancy subtype characterized by poor prognosis. The pursuit of effective therapeutic approaches for this subtype is considerably challenging. Notably, recent research has illuminated the key role of the tricarboxylic acid cycle in cancer metabolism and the complex landscape of tumor development. Concurrently, an emerging body of evidence underscores the noteworthy role that long non-coding RNAs play in the trajectory of breast cancer development. Despite this growing recognition, the exploration of whether long non-coding RNAs can influence breast cancer progression by modulating the tricarboxylic acid cycle has been limited. Moreover, the underlying mechanisms orchestrating these interactions have not been identified. Methods: The expression levels of LINC00571 and IDH2 were determined through the analysis of the public TCGA dataset, transcriptome sequencing, qRT‒PCR, and Western blotting. The distribution of LINC00571 was assessed using RNA fluorescence in situ hybridization. Alterations in biological effects were evaluated using CCK-8, colony formation, EdU, cell cycle, and apoptosis assays and a tumor xenograft model. To elucidate the interaction between LINC00571, HNRNPK, and ILF2, RNA pull-down, mass spectrometry, coimmunoprecipitation, and RNA immunoprecipitation assays were performed. The impacts of LINC00571 and IDH2 on tricarboxylic acid cycle metabolites were investigated through measurements of the oxygen consumption rate and metabolite levels. Results: This study revealed the complex interactions between a novel long non-coding RNA (LINC00571) and tricarboxylic acid cycle metabolism. We validated the tumor-promoting role of LINC00571. Mechanistically, LINC00571 facilitated the interaction between HNRNPK and ILF2, leading to reduced ubiquitination and degradation of ILF2, thereby stabilizing its expression. Furthermore, ILF2 acted as a transcription factor to enhance the expression of its downstream target gene IDH2. Conclusions: Our study revealed that the LINC00571/HNRNPK/ILF2/IDH2 axis promoted the progression of triple-negative breast cancer by regulating tricarboxylic acid cycle metabolites. This discovery provides a novel theoretical foundation and new potential targets for the clinical treatment of triple-negative breast cancer. [ABSTRACT FROM AUTHOR]

DC Beads and CalliSpheres are commonly used microspheres in clinical transcatheter arterial chemoembolization, but these microspheres cannot be visualized by themselves. Therefore, in our previous study, we developed multimodal imaging nano-assembled microspheres (NAMs), which are visualized under CT/MR and the location of embolic microspheres can be determined during postoperative review, facilitating the evaluation of embolic areas and guiding subsequent treatment. Moreover, the NAMs can be carried with positively and negatively charged drugs, increasing the choice of drugs. Systematic comparative analysis of the pharmacokinetics of NAMs with commercially available DC Bead and CalliSpheres microspheres is important for evaluating the clinical application of NAMs. In our study, we compared the similarities and differences between NAMs and two drug-eluting beads (DEBs) in respect to drug loading capacity, drug release profiles, diameter variation and morphological characteristics. The results indicate that NAMs had good drug delivery and release characteristics as well as DC Bead and CalliSpheres in vitro experimental stage. Therefore, NAMs have a good application prospect in transcatheter arterial chemoembolization treatment of hepatocellular carcinoma. [ABSTRACT FROM AUTHOR]

Background: N6-methyladenosine (m6A) is the most common post-transcriptional modification at the RNA level. However, the exact molecular mechanisms of m6A epigenetic regulation in breast cancer remain largely unknown and need to be fully elucidated. Methods: The integrating bioinformatics analyses were used to screen clinical relevance and dysregulated m6A "reader" protein YTHDF1 in breast cancer from TCGA databases, which was further validated in a cohort of clinical specimens. Furthermore, functional experiments such as the CCK-8 assay, EdU assay, wound healing assay, transwell invasion assay and cell cycle assay were used to determine the biological role of YTHDF1 in breast cancer. RIP, m6A-IP, and CLIP assays were used to find the target of YTHDF1 and further verification by RT-qPCR, western blot, polysome profiling assay. The protein–protein interaction between YTHDF1 and FOXM1 was detected via co-immunoprecipitation. Results: Our study showed that YTHDF1 was overexpressed in breast cancer cells and clinical tissues specimens. At the same time, the high expression level of YTHDF1 was positively correlated with tumor size, lymph node invasion, and distant metastasis in breast cancer patients. YTHDF1 depletion repressed the proliferation, invasion and epithelial-mesenchymal transformation (EMT) and induced G0/G1 phase cell cycle arrest of breast cancer cells in vitro and in vivo. We also demonstrated that FOXM1 is a target of YTHDF1. Through recognizing and binding to the m6A-modified mRNA of FOXM1, YTHDF1 accelerated the translation process of FOXM1 and promoted breast cancer metastasis. Whereas overexpression of FOXM1 in breast cancer cells partially counteracted the tumor suppressed effects caused by YTHDF1 silence, which further verified the regulatory relationship between YTHDF1 and FOXM1. Conclusion: Our study reveals a novel YTHDF1/FOXM1 regulatory pathway that contributes to metastasis and progression of breast cancer, suggesting that YTHDF1 might be applied as a potential biomarker and therapeutic target. That also advances our understanding of the tumorigenesis for breast cancer from m6A epigenetic regulation. [ABSTRACT FROM AUTHOR]

Purpose: Papillary thyroid cancer (PTC) patients could obtain poor prognosis if they have lymph node metastasis, identification of informative and robust biomarkers for predicting cervical lymph node metastasis is critical for improving clinical decision-making and patient prognosis. Materials and Methods: In this study, we analyzed the expression of X box binding protein 1 spliced-form (XBP1s) in 41 PTC tissue samples and extended our findings using public databases, then we investigated how XBP1s' contributed to PTC progression in vitro. Results: We found that XBP1s' expression was lower in PTC patients with cervical lymph node metastasis than non-metastasis patients by immunohistochemical analysis. With publicly accessible dataset, we showed that the XBP1 transcription was significantly decreased in thyroid cancer (TC) tissues with lymph node metastasis as compared to that without lymph node metastasis. Moreover, we also found that XBP1 expression was significantly correlated with patients' gender, T classification, lymph node metastasis and PTC stages, and low XBP1 expression was associated with poor diseases free survival (DFS). In vitro, XBP1s overexpression could inhibit the invasion, migration, and wound healing capacity of PTC cells. Mechanistically, overexpression of XBP1s could enhance the expression of classical epithelial–mesenchymal transition (EMT) markers such as ZO-1 and E-cadherins, and downregulated N-cadherin in BCPAP cells. Conclusion: These findings suggest that XBP1s is a prognostic maker for thyroid carcinoma patients, and sustaining XBP1s expression might be a new strategy to control PTC progression. [ABSTRACT FROM AUTHOR]

Tumor-associated macrophages (TAMs) are closely related to poor prognosis in triple-negative breast cancer (TNBC). Thus, gaining insight into how TAMs support cancer progression could contribute to effective therapies. We utilized the 4 T1 murine TNBC cell line and murine bone marrow-derived macrophages to assess TAM-mediated pro-proliferative effects in vivo and in vitro. Further, Transcriptional analysis was performed to identify pathways activated in TAM-stimulated 4 T1 cells. We also explored the therapeutic efficacy of combining a mitogen-activated protein kinase kinase (MEK) inhibitor with TAM-targeted therapy using a TNBC mouse model. We found that the presence of TAMs was significantly associated with proliferating cancer cells in a TNBC mouse model. Moreover, RNA sequencing analysis showed that TAMs could enhance mitogen-activated protein kinase (MAPK) pathway activation in 4 T1 cells compared to that in control cells. Further, the depletion of TAMs by clodronate liposomes significantly reduced MAPK pathway activation in vivo. In addition, the blockade of MAPK signaling by a MEK inhibitor repressed TAM-mediated cancer cell proliferation. Most importantly, MEK inhibition combined with macrophage depletion significantly suppressed tumor growth and increased T lymphocyte infiltration in a TNBC model. Our study suggests the possibility that TAM-induced MAPK pathway activation promotes cancer cell proliferation. Thus, MEK inhibition combined with macrophage depletion might represent an effective treatment for TNBC. • TAMs are significantly associated with proliferating cancer cells. • TAMs could enhance MAPK pathway activation in 4 T1 cells. • MEK inhibition combined with macrophage depletion shows therapeutic effects in a TNBC model. [ABSTRACT FROM AUTHOR]