Diagnostic Value of High Frame Rate Contrast-enhanced Ultrasonography and Post-processing Contrast Vector Imaging for Evaluation of Focal Liver Lesions: A Feasibility Study.
- 作者列表："Yoo J","Lee JM
:This study evaluated the feasibility of contrast vector imaging (CVI) to characterize focal liver lesions. From July to October 2019, we prospectively enrolled 30 patients with focal liver lesions (hepatocellular carcinoma [HCC] [n = 19], metastasis [n = 8], combined HCC-cholangiocarcinoma [CC] [n = 1], intra-hepatic CC [n = 1] and sclerosed hemangioma [n = 1]). Contrast-enhanced ultrasound (CEUS) was performed with high frame rate contrast harmonic imaging technique by one radiologist, and post-processing CVI was obtained and analyzed by two radiologists. On combined CVI with CEUS, the staining pattern was significantly predominant in HCCs (9/11, 81.8%), while peripheral rim was frequent in non-HCCs (5/8, 62.5%) (p = 0.020). HCCs exhibited feeding arteries (8/11, 45.5%) and high velocity variance (10/11, 90.9 %), whereas non-HCCs showed detour pattern (4/8, 50.0%) with either a high or low velocity variance (4/8, 50.0%, both), with no significant inter-group differences (p = 0.052 and 0.080, respectively). In conclusion, CVI was feasible and provided quantitative and multi-parametric information of different types of hepatic tumors.
: 本研究评估了对比向量成像 (CVI) 表征肝脏局灶性病变的可行性。从 2019 年 7 月至 10 月，我们前瞻性纳入了 30 例肝脏局灶性病变 (肝细胞癌 [HCC] [n = 19]，转移 [n = 8],联合 HCC-胆管癌 [CC] [n = 1]，肝内 CC [n = 1] 和硬化性血管瘤 [n = 1])。由 1 名放射科医师采用高帧频对比度谐波成像技术进行超声造影 (CEUS)，由 2 名放射科医师获得后处理 CVI 并进行分析。在 CVI 联合 CEUS 时，HCCs 中染色模式显著占优势 (9/11，81.8%)，而周边缘在非 HCCs 中常见 (5/8，62.5%) (p = 0.020)。Hcc 表现出供血动脉 (8/11，45.5%) 和高速方差 (10/11，90.9%)，而非 hcc 表现出绕行模式 (4/8，50.0%) 具有高或低速度方差 (4/8，50.0%，均为)，组间差异无统计学意义 (分别为 p = 0.052 和 0.080)。总之，CVI 是可行的，提供了不同类型肝肿瘤的定量和多参数信息。
METHODS::Aims: Radiotherapy is predominantly used as one of the treatment modalities to treat local tumor in colorectal cancer (CRC). Hindrance in disease treatment can be attributed to radio-tolerance of cancer stem cells (CSCs) subsistence in the tumor. Understanding the radio-resistant property of CSCs might help in the accomplishment of targeted radiotherapy treatment and increased disease-free survival. Telomeric RAP1 contributes in modulation of various transcription factors leading to aberrant cell proliferation and tumor cell migration. Therefore, we investigated the role of RAP1 in maintaining resistance phenotype and acquired stemness in radio-resistant cells.Main Methods: Characterization of HCT116 derived radio-resistant cell (HCT116RR) was performed by cell survival and DNA damage profiling. RAP1 silenced cells were investigated for DNA damage and expression of CSC markers through western blotting and Real-time PCR post-irradiation. Molecular docking and co-immunoprecipitation study were performed to investigate RAP1 and KLF4 interaction followed by RAP1 protein status profiling in CRC patient.Key findings: We established radio-resistant cells, which showed tolerance to radiotherapy and elevated expression of CSC markers along with RAP1. RAP1 silencing showed enhanced DNA damage and reduced expression of CSC markers post-irradiation. We observed strong physical interaction between RAP1 and KLF4 protein. Furthermore, higher RAP1 expression was observed in the tumor of CRC patients. Dataset analysis also revealed that high expression of RAP1 expression is associated with poor prognosis.Significance: We conclude that higher expression ofRAP1 implicates its possible role in promoting radio-resistance in CRC cells by modulating DNA damage and CSC phenotype.
METHODS::Cancer stem-like cells are rare immortal cells within tumor, which are thought to play important roles in ionizing radiation (IR) therapy-resistance. Quercetin is a natural flavonoid with potential anti-cancer properties without significant cytotoxicity in normal tissues. In this study, we demonstrated that quercetin-IR combination treatment exhibited more dramatic anti-cancer effect than either quercetin or IR treatment alone via targeting colon cancer stem cells (CSCs) and inhibiting the Notch-1 signaling. These effects were further verified by in vivo studies which showed remarkable decrease of the CSCs markers and the expression of Notch-1 signaling proteins in human colon cancer xenografts in nude mice. Co-treatment with quercetin and low dose of radiation significantly reduced the expressions of all five proteins of γ-secretase complex in HT-29 and DLD-1 cells. In addition, ectopic expression of the Notch intracellular domain (NICD) partly reversed the inhibition effects by the combination therapy. In conclusion, our results indicated that the combination of quercetin (20 μM) and IR (5Gy) might be a promising therapeutic strategy for colon cancer treatment by targeting colon cancer stem-like cells and inhibiting the Notch-1 signaling. In future studies, we intend to further explore the potential therapeutic efficacy of the quercetin-radiation combination treatment in clinical trials.
METHODS:OBJECTIVES:Long-term prevention of metastatic disease remains a challenge in locally advanced rectal cancer, and robust pretreatment prognostic factors for metastatic progression are lacking. We hypothesized that detecting circulating tumor-specific DNA (ctDNA) based on hypermethylation of the neuropeptide Y gene (meth-ctDNA) could be a prognostic marker in the neoadjuvant setting; we examined this in a secondary, explorative analysis of a prospective trial. MATERIALS AND METHODS:Serum samples were prospectively collected in a phase III trial for locally advanced rectal cancer. Positivity for and fractional abundance of meth-ctDNA in baseline samples were estimated. Overall survival (OS) and the rate of distant metastases were compared between meth-ctDNA positive and negative patients; other prognostic factors were controlled for in multivariate Cox regression. Importance of quantitative load was examined by considering the fractional abundance of meth-ctDNA relative to total circulating DNA. RESULTS:Baseline serum samples were available for 146 patients. In total, 30 patients had presence of meth-ctDNA, with no correlation with cT (P=0.8) or cN (P=0.6) stages. Median follow-up was 10.6 years for OS and 5.1 years for freedom from distant metastases. Patients with meth-ctDNA had significantly worse 5-year OS (47% vs. 69%), even when controlling for other prognostic factors (hazard ratio=2.08; 95% confidence interval, 1.23-1.51). This seemed mainly driven by disparity in the rate of distant metastases (55% vs. 72% at 5 y, P=0.01); hazard ratio=2.20 (95% confidence interval, 1.19-4.07, P=0.01) in multivariate analysis. Increased quantitative load was highly significant for worse outcomes. CONCLUSIONS:Meth-ctDNA could be a potential prognostic marker in the neoadjuvant setting and may, if validated, identify patients at increased risk of distant metastases.