Circular RNAs (circRNAs) are connected at the 3′ and 5′ ends by exon or intron cyclization, forming a complete ring structure. circRNA is more stable and conservative than linear RNA and abounds in various organisms. In recent years, increasing numbers of reports have found that circRNA plays a major role in the biological functions of a network of competing endogenous RNA (ceRNA). circRNAs can compete together with microRNAs (miRNAs) to influence the stability of target RNAs or their translation, thus, regulating gene expression at the transcriptional level. circRNAs are involved in biological processes such as tumor cell proliferation, apoptosis, invasion, and migration as ceRNAs. circRNAs, therefore, represent promising candidates for clinical diagnosis and treatment. Here, we review the progress in studying the role of circRNAs as ceRNAs in tumors and highlight the participation of circRNAs in signal transduction pathways to regulate cellular functions.
Immune checkpoint blockade targeting PD-1/PD-L1 has promising therapeutic efficacy in a variety of tumors, but resistance during treatment is a major issue. In this review, we describe the utility of PD-L1 expression levels, mutation burden, immune cell infiltration, and immune cell function for predicting the efficacy of PD-1/PD-L1 blockade therapy. Furthermore, we explore the mechanisms underlying immunotherapy resistance caused by PD-L1 expression on tumor cells, T cell dysfunction, and T cell exhaustion. Based on these mechanisms, we propose combination therapeutic strategies. We emphasize the importance of patient-specific treatment plans to reduce the economic burden and prolong the life of patients. The predictive indicators, resistance mechanisms, and combination therapies described in this review provide a basis for improved precision medicine.
Hepatic choline levels and ADCs may allow monitoring of therapeutic responses of HCC to TACE although larger, more definitive and quantitative studies with clinical end points are needed.
Purpose:To investigate the value of in vivo proton magnetic resonance spectroscopy (MRS) in the assessment of large focal hepatic lesions and to measure the metabolite change of hepatocellular carcinoma (HCC) after transcatheter arterial chemoembolization (TACE) using 3.0-T scanner.
Materials and Methods:In this prospective study, 43 consecutive patients with large (not less than 3 cm in diameter) hepatic tumors and eight normal volunteer were included. MRS of the lesions in addition to uninvolved liver parenchyma was carried out using a whole-body 3.0-T scanner. Among the patients with proven HCC, eight lesions were evaluated before and two to five days after TACE. The choline-to-lipid (cho/lipid) ratio was measured by dividing the peak area of choline at 3.2 ppm by the peak area of lipid at 1.3 ppm. The sensitivity and specificity profiles of MRS in the diagnosis of malignant hepatic tumors were determined by plotting empirical receiver operating characteristic (ROC) curve. The mean cho/lipid ratios in different groups before and after TACE were also measured.
Results:The technical success rate for MRS was 90% (53/ 59). The ROC curve showed proton MRS has moderate discriminating ability in diagnosing malignant hepatic tumors, although the sensitivity was less than 50% while 1-specificity was less than 20%. The area under the curve was 0.71 (P Ͻ 0.05). The mean Ϯ 1 standard error (SE) of cho/lipid ratios for uninvolved liver (N ϭ 8), benign tumor (N ϭ 8), and malignant tumor (N ϭ 21; 19 HCC, one angiosarcoma, and one lymphoma) were 0.06 Ϯ 0.02, 0.02 Ϯ 0.02, and 0.17 Ϯ 0.05, respectively. A significantly statistical difference (ANOVA planned contrast test, P ϭ 0.01 and Games-Howell procedure, P ϭ 0.03) was achieved in the mean cho/lipid ratio between malignant and benign tumors. The mean cho/lipid ratios were significantly decreased from 0.23 Ϯ 0.11 before TACE to 0.01 Ϯ 0.00 after the treatment (t ϭ 2.01, P Ͻ 0.05, one-tail paired t-test; z ϭ -2.37, P Ͻ 0.05, Wilcoxon Signed Ranks Test).
Conclusion:In vivo proton MRS is technically feasible for the evaluation of focal hepatic lesions. The technique has potential in the detection of early metabolite change in malignant liver tumors after TACE but limitation still exists in clear differentiation between normal liver and benign and malignant tumor.
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