Developing ultrasensitive contrast agents for the early detection of malignant tumors in liver is highly demanded. Constructing hepatic tumors specific targeting probes could provide more sensitive imaging information but still faces great challenges. Here we report a novel approach for the synthesis of ultra-small Fe3O4 nanoparticles conjugated with c(RGDyK) and their applications as active-target T1-weighted magnetic resonance imaging (MRI) contrast agent (T1-Fe3O4) for imaging tiny hepatic tumors in vivo. RGD-modified T1-Fe3O4 nanoprobes exhibited high r1 of 7.74 mM-1s-1 and ultralow r2/r1 of 2.8 at 3 T, reflecting their excellent T1 contrast effect at clinically relevant magnetic field. High targeting specificity together with favorable biocompatibility and strong ability to resist against non-specific uptake were evaluated through in vitro studies. Owing to the outstanding properties of tumor angiogenesis targeting with little phagocytosis in liver parenchyma, hepatic tumor as small as 2.2 mm was successfully detected via the T1 contrast enhancement of RGD-modified T1-Fe3O4. It is emphasized that this is the first report on active-target T1 imaging of hepatic tumors, which could not only significantly improve diagnostic sensitivity, but also provide post therapeutic assessments for patients with liver cancer.
• LARC responded well after neoadjuvant chemoradiotherapy with lower pre-D . • LARC responded well with greater increases in mean ADC and D . • The change ratio of D (r∆D ) had a relatively better diagnostic performance.
Cervical cancer is the third most common type of cancer in women, and microRNAs play an important role in this type of cancer. The elevated expression of miR-146a is involved in the pathogenesis of cancers generally, but its role in cervical cancer has not been fully elucidated. In the present study, we assessed the expression of miR-146a in G>C polymorphisms and confirmed that the overexpression of miR-146a promoted cervical cancer cell viability. The recombinant expression plasmids pre-miR-146a-G or pre-miR-146a-C including single nucleotide polymorphisms (SNP) were successfully constructed. Pre-miR-146a-G or pre-miR-146a-C was transfected into cervical cancer cells or immortalized non-tumorigenic cells and the expression of miR-146a was evaluated by real-time PCR. The cell viability, cell-cycle analysis and apoptosis were assessed using Cell Counting Kit-8 assay (CCK-8), flow cytometry and cleaved caspase-3 protein expression, respectively. The expression of interleukin 1 receptor associated kinase 1 (IRAK1), TNF receptor-associated factor 6 (TRAF6) and cyclin D1 was assessed following the transfection with a miR-146a mimic or a negative control. The cell viability and the number of S-phase cells increased after transfection with miR-146a mimic or an IRAK1 or TRAF6 interference fragment. After transfection, IRAK1 and TRAF6 protein expression was downregulated and the expression of cyclin D1 was upregulated, however apoptosis and cleaved caspase-3 were not affected. Polymorphisms in miR-146a precursor may be linked to the expression of miR-146a and may be a potential target for cervical cancer therapy.
Background Detecting normal-sized metastatic pelvic lymph nodes (LNs) in cervical cancers, although difficult, is of vital importance. Purpose To investigate the value of diffusion-weighted-imaging (DWI), tumor size, and LN shape in predicting metastases in normal-sized pelvic LNs in cervical cancers. Material and Methods Pathology confirmed cervical cancer patients with complete magnetic resonance imaging (MRI) were documented from 2011 to 2016. A total of 121 cervical cancer patients showed small pelvic LNs (<5 mm) and 92 showed normal-sized (5-10 mm) pelvic LNs (39 patients with 55 nodes that were histologically metastatic, 53 patients with 71 nodes that were histologically benign). Preoperative clinical and MRI variables were analyzed and compared between the metastatic and benign groups. Results LN apparent diffusion coefficient (ADC) values and short-to-long axis ratios were not significantly different between metastatic and benign normal-sized LNs (0.98 ± 0.15 × 10 vs. 1.00 ± 0.18 × 10 mm/s, P = 0.45; 0.65 ± 0.16 vs. 0.64 ± 0.16, P = 0.60, respectively). Tumor ADC value of the metastatic LNs was significantly lower than the benign LNs (0.98 ± 0.12 × 10 vs. 1.07 ± 0.21 × 10 mm/s, P = 0.01). Tumor size (height) was significantly higher in the metastatic LN group (27.59 ± 9.18 mm vs. 21.36 ± 10.40 mm, P < 0.00). Spiculated border rate was higher in the metastatic LN group (9 [16.4%] vs. 3 [4.2%], P = 0.03). Tumor (height) combined with tumor ADC value showed the highest area under the curve of 0.702 ( P < 0.00) in detecting metastatic pelvic nodes, with a sensitivity of 59.1% and specificity of 78.8%. Conclusions Tumor DWI combined with tumor height were superior to LN DWI and shape in predicting the metastatic state of normal-sized pelvic LNs in cervical cancer patients.
• The K , K and V values correlated with synchronous distant metastasis. • Higher K , K and V values were noted among patients with metastasis. • DCE-MRI parameters might represent a prognostic indicator for synchronous distant metastases.
Objectives: To determine the diagnostic ability of cervical mucosa radiomics signature of sagittal T2WI and T1 contrast-enhanced (CE) imaging in detecting early-stage cervical cancers with negative MRI. Methods: Preoperative images of postoperative pathology confirmed early-stage cervical cancer patients and normal cervix patients admitted to our hospital between January 2013 and December 2020 were retrospectively reviewed. Patients with cancer signals on T2WI, T1CE and DWI were deleted. Regions of interests (ROIs) were delineated on cervical mucosa (from cervical canal to cervical dome) with 5 mm width on sagittal T2WI and T1CE. The maximum-relevance and minimumredundancy (mRMR) and least absolute shrinkage and selection operator (LASSO) methods were used for the calculation of radiomics signature scores. Diagnostic performance was assessed and compared between radiomics prediction models (model 1: T1CE; model 2: T2WI; model 3: model one combined with model 2). Differential diagnostic ability of radiomics signature in detecting lymphatic vascular space invasion (LVSI) was further explored. Results: Diagnostic performance of model three was higher than model 1 and model 2 both in primary (model 3 0.874, model 1 0.857, model 2 0.816) and validation (model 3 0.853, model 1 0.847, model 2 0.634) cohorts. Model 3 showed statistical diagnostic difference compared with model 2 (primary p = 0.008, validation p = 0.000). However, the diagnostic improvement ability of model 3 showed no statistical difference compared with model 1 (primary p = 0.351, validation p = 0.739). Diagnostic efficiency of model 3 in detecting LVSI was not apparent (AUC 0.64). Conclusions: Radiomics analysis of cervical mucosa combining T1CE and T2WI is promising for predicting MRI invisible early-stage cervical cancers, however further ability in detecting LVSI was not apparent. Advances in knowledge: Conventional MRI was originally defined as meaningless in very early-stage cervical cancers. However, whether MRI radiomics analysis of cervical mucosa can detecting tiny changes of invisible early stage cervical cancers has not been researched yet.
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