The KD is a safe and efficacious therapy for intractable childhood epilepsy in Chinese children. The influence of age on efficacy is worth further investigation.
Higher De Ritis ratio could be predictive for worse pathological outcomes and higher BCR in localized prostate cancer patients. A predictive model which incorporates De Ritis ratio, Gleason Score and pathological tumor stage could help risk stratification for BCRFS.
Prostate cancer is the most common cancer among men in the Unites States. The cytokine IL-6 activates several prostate cancer pathways, but its upstream trans-signaling pathway remains poorly understood. In this study, we evaluated the role of IL-6 in PDCD4 gene expression and how the microRNA miR-21 regulates this process in prostate cancer cell lines PC-3 and LNCaP. The expression pattern of PDCD4 from samples from human prostate cancer, precancerous lesions, and benign prostatic hyperplasia was investigated by immunohistochemistry. PDCD4 transcription and translation were detected by quantitative real-time PCR (qRT-PCR) and Western blot analysis, respectively. The targeted modulation of PDCD4 by miR-21 was analyzed in PC-3 and LNCaP cells, and the effect of IL-6 on the expression of PDCD4 was studied in vitro. PDCD4 expression in samples from the 3 tissue types progressively increased, and the expression levels of PDCD4 and prostate-specific antigen were negatively correlated. The levels of PDCD4 mRNA and protein in PC-3 and LNCaP cells transfected with anti–miR-21 constructs were lower than those in control cells. The expression of PDCD4 was inhibited by IL-6, but this effect was weakened in cell lines with low expression of miR-21. Our study demonstrates that the regulation of PDCD4 by miR-21 is targeted and IL-6 inhibits expression of the PDCD4 gene in PC-3 and LNCaP cells through the targeted function of miR-21 on PDCD4. These findings support the feasibility of future efforts for diagnosis and gene therapy for prostate cancer that are based on IL-6, miR-21, and PDCD4.
Radiomics studies to predict lymph node (LN) metastasis has only focused on either primary tumor or LN alone. However, combining radiomics features from multiple sources may reflect multiple characteristic of the lesion thereby increasing the discriminative performance of the radiomic model. Therefore, the present study intends to evaluate the efficiency of integrative nomogram, created by combining clinical parameters and radiomics features extracted from gross tumor volume (GTV), peritumoral volume (PTV) and LN, for the preoperative prediction of LN metastasis in clinical cT1N0M0 adenocarcinoma. A primary cohort of 163 patients (training cohort, 113; and internal validation cohort, 50) and an external validation cohort of 53 patients with clinical stage cT1N0M0 were retrospectively included. Features were extracted from three regions of interests (ROIs): GTV; PTV (5.0 mm around the tumor) and LN on pre-operative contrast enhanced computed tomography (CT). LASSO logistic regression method was used to build radiomic signatures. Multivariable regression analysis was used to build a nomogram. The performance of the nomogram was assessed with respect to its calibration, discrimination, and clinical usefulness. The discriminative performance of nomogram was validated both internally and externally. The radiomic signatures using the features of GTV, PTV and LN showed a good ability in predicting LN metastasis with an area under the curve (AUC) of 0.74 (95% CI 0.60–0.88), 0.72 (95% CI 0.57–0.87) and 0.64 (95% CI 0.48–0.80) respectively in external validation cohort. The integration of different signature together further increases the discriminatory ability: GTV + PTV (GPTV): AUC 0.75 (95% CI 0.61–0.89) and GPTV + LN: AUC 0.76 (95% CI 0.61–0.91) in external validation cohort. An integrative nomogram of clinical parameters and radiomic features demonstrated further increase in discriminatory ability with AUC of 0.79 (95% CI 0.66–0.93) in external validation cohort. The nomogram showed good calibration. Decision curve analysis demonstrated that the radiomic nomogram was clinically useful. The integration of information from clinical parameters along with CT radiomics information from GTV, PTV and LN was feasible and increases the predictive performance of the nomogram in predicting LN status in cT1N0M0 adenocarcinoma patients suggesting merit of information integration from multiple sources in building prediction model.
Background/Aims: This study investigated whether microRNA-214 (miR-214) targets mitofusin-2 (Mfn2) in the process of fibroblast differentiation of adipose-derived mesenchymal stem cells (ADMSCs) during pelvic floor dysfunction (PFD) in Sprague Dawley (SD) rats with birth trauma. Methods: The ADMSCs were isolated from 4-6 week male SD rats (n = 20) and were cultured and divided into the blank, miR-214 mimic negative control (NC), miR-214 mimic, miR-214 inhibitor NC, miR-214 inhibitor, empty vector, Mfn2 over-expression and miR-214 + Mfn2 over-expression groups. Fibroblast differentiation of ADMSCs was measured with immunocytochemistry and immunofluorescence methods. The expression of miR-214 and the mRNA and protein expression of Mfn2, FSP1, Collagen I, Collagen III, Elastin, LOX, Fibulin-5, PPAR-γ and Runx2 were detected using quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting, respectively. A dual-luciferase reporter assay was performed to confirm whether Mfn2 was the target gene of miR-214. Results: During ADMSC differentiation into fibroblasts, miR-214 expression was up-regulated, but the expression of Mfn2 was down-regulated. Fibroblast differentiation of ADMSCs was promoted in the miR-214 mimic group but was inhibited in the miR-214 inhibitor and Mfn2 over-expression groups. The expression of Mfn2 was decreased, but the expression of FSP1, Collagen I, Collagen III, Elastin, LOX, Fibulin-5, PPAR-γ or Runx2 was increased in the miR-214 mimic group; the miR-214 inhibitor group and Mfn2 over-expression group exhibited the opposite results. Mfn2 was the target gene of miR-214. Conclusions: The study provided strong evidence that miR-214 could promote fibroblast differentiation of ADMSCs by down-regulating Mfn2 to improve PFD in SD rats with birth trauma.
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