Hongyuan Jia

Cancer-associated fibroblasts (CAFs) are key players in cancer development and therapy, and they exhibit multifaceted roles in the tumor microenvironment (TME). From their diverse cellular origins, CAFs undergo phenotypic and functional transformation upon interacting with tumor cells and their presence can adversely influence treatment outcomes and the severity of the cancer. Emerging evidence from single-cell RNA sequencing (scRNA-seq) studies have highlighted the heterogeneity and plasticity of CAFs, with subtypes identifiable through distinct gene expression profiles and functional properties. CAFs influence cancer development through multiple mechanisms, including regulation of extracellular matrix (ECM) remodeling, direct promotion of tumor growth through provision of metabolic support, promoting epithelial-mesenchymal transition (EMT) to enhance cancer invasiveness and growth, as well as stimulating cancer stem cell properties within the tumor. Moreover, CAFs can induce an immunosuppressive TME and contribute to therapeutic resistance. In this review, we summarize the fundamental knowledge and recent advances regarding CAFs, focusing on their sophisticated roles in cancer development and potential as therapeutic targets. We discuss various strategies to target CAFs, including ECM modulation, direct elimination, interruption of CAF-TME crosstalk, and CAF normalization, as approaches to developing more effective treatments. An improved understanding of the complex interplay between CAFs and TME is crucial for developing new and effective targeted therapies for cancer.

PURPOSE: The use of contrast-enhanced sonography (CEUS) has yielded promising results in the differentiation of thyroid nodules. We conducted this meta-analysis to assess its performance in identifying and distinguishing between benign and malignant thyroid nodules. METHODS: PubMed, Medline, Embase, and the Cochrane Library were searched for studies published through the end of December 2013. Sensitivity, specificity, positive and negative likelihood ratios, diagnostic odds ratio, and area under the curve were calculated. RESULTS: A total of 13 studies were included in this meta-analysis. For the diagnosis of malignant thyroid nodules worldwide, the overall mean rates of sensitivity and specificity of CEUS were 90% (95% confidence interval [CI], 88-93%) and 86% (95% CI, 83-89%), respectively. The summary diagnostic odds ratio was 52.83 (95% CI, 21.71-128.55), and the area under the curve for the summary receiver operating characteristic curve was 0.94 (95% CI, 0.90-0.98). CONCLUSIONS: This meta-analysis indicates that CEUS may be a valuable supplemental method, with high rates of sensitivity and specificity, to use for identifying and distinguishing between benign and malignant thyroid nodules.

Uric acid (UA) released from dying cells has been recognized by the immune system as a danger signal. In response to UA, dendritic cells (DC) in the immune system mature and enhance the T cell response to foreign antigens. It is conceivable that the antitumor immunity of a tumor vaccine could be promoted by the administration of UA. To test this concept, we applied UA as an adjuvant to a DC-based vaccine, and discovered that the administration of UA as an adjuvant significantly enhanced the ability of the tumor lysate-pulsed DC vaccine in delaying the tumor growth. The antitumor activity was achieved with adoptively transferred lymphocytes, and both CD8(+) T cells and NK cells were required to achieve effective immunity. This resulted in an increased accumulation of activated CD8(+) T cells and an elevated production of IFN-γ. Collectively, our study shows that the administration of UA enhances the antitumor activity of tumor lysate-pulsed DC vaccine, thus providing the preclinical rationale for the application of UA in DC-based vaccine strategies.

OBJECTIVE: To assess the performance of contrast-enhanced ultrasound (CE-US) in the differential diagnosis of malignant and benign ovarian tumors. METHODS: We conducted a comprehensive literature search of PubMed and EMBASE to identify published articles evaluating the diagnostic potential of CE-US for the differentiation of benign and malignant ovarian tumors. Inclusion criteria were: (1) the study assessed the accuracy (or sensitivity and specificity) of CE-US for diagnosis of benign and malignant ovarian tumors; (2) it used surgery and histopathology as the reference standard for distinguishing between benign and malignant tumors; (3) it included data allowing construction of a 2×2 contingency table for true- and false-positives and negatives. We present summary sensitivity, specificity, diagnostic odds ratio (OR) and areas under the summary receiver-operating characteristics curves (AUCs). RESULTS: Preliminary screening identified 103 papers, of which 11 fulfilled our predefined inclusion criteria and underwent final analysis. The pooled sensitivity and specificity of CE-US for diagnosis of benign and malignant ovarian tumors were 93% (95% CI, 89-96%) and 95% (95% CI, 92-96%), respectively. The pooled diagnostic OR was 171.2 (95% CI, 65.9-444.6) and the AUC was 0.98. I(2) values of sensitivity, specificity and diagnostic OR were 38.3%, 31.7% and 48.4%, respectively, all indicating moderate heterogeneity. CONCLUSIONS: The evidence from available studies suggests CE-US is useful for discriminating between benign and malignant ovarian tumors; however, further studies are needed to examine whether CE-US has improved diagnostic test accuracy compared with that of standard two-dimensional Doppler sonography.