Receptor levels are a key mechanism by which cells regulate their response to stimuli. The levels of estrogen receptor-α (ERα) impact breast cancer cell proliferation and are used to predict prognosis and sensitivity to endocrine therapy. Despite the clinical application of this information, it remains unclear how different cellular processes interact as a system to control ERα levels. To address this question, experimental results from the ERα-positive human breast cancer cell line (MCF-7) treated with 17-β-estradiol or vehicle control were used to develop a mass-action kinetic model of ERα regulation. Model analysis determined that RNA dynamics could be captured through phosphorylated ERα (pERα)-dependent feedback on transcription. Experimental analysis confirmed that pERα-S118 binds to the estrogen receptor-1 (ESR1) promoter, suggesting that pERα can feedback on ESR1 transcription. Protein dynamics required a separate mechanism in which the degradation rate for pERα was 8.3-fold higher than nonphosphorylated ERα. Using a model with both mechanisms, the root mean square error was 0.078. Sensitivity analysis of this combined model determined that while multiple mechanisms regulate ERα levels, pERα-dependent feedback elicited the strongest effect. Combined, our computational and experimental results identify phosphorylation of ERα as a critical decision point that coordinates the cellular circuitry to regulate ERα levels.
To evaluate the magnetic resonance diffusion-weighted imaging (DWI) in the detection of early ankylosing spondylitis and explore the manifestations of ankylosing spondylitis on whole body DWI (WB-DWI).A total of 16 patients with early ankylosing spondylitis (AS) and 18 patients with low back pain (LBP) were recruited. Subchondral bone marrow apparent diffusion coefficient (ADC) in bilateral ilium and sacrum along sacroiliac joints were compared. An independent sample t-test (SPSS 16.0, SPSS, Chicago, III) was utilized to analyze the ADC value differences between groups. P < 0.05 denoted statistical significance. The mean ADC values of focal lesions in AS patients were also measured. Whole body diffusion weighted imaging was performed in additional 8 clinical confirmed AS patients and analyzed with the techniques of maximum intensity projection (MIP) and multiplanar reconstruction (MPR) in comparison with conventional MRI images to investigate the detectability of AS lesions with whole body DWI.Mean ADC values in 16 AS patients were (0.51 ± 0.13)×10(-3)mm(2)/s in ilium and (0.49 ± 0.17)×10(-3)mm(2)/s in sacrum. Mean ADC values in 18 LBP patients were (0.32 ± 0.06)×10(-3)mm(2)/s in ilium and (0.31 ± 0.08)×10(-3)mm(2)/s in sacrum. The ADC value in AS patients were statistically significantly greater than those in ilium and sacrum of LBP patients. Whole body DWI detected abnormalities in 8 AS patients within bilateral sacroiliac joints and other sites corresponding to the clinical symptoms of patients. The mean ADC values of focal lesions of this patient cohort were (1.31 ± 0.38)×10(-3)mm(2)/s in sacrum and (1.18 ± 0.27)×10(-3)mm(2)/s in ilium.Subchondral marrow ADC values along sacroiliac joints allow the differentiation of patients with early AS from LBP patients. In conjunctions with such post-processing techniques as MIP and MPR, WB-DWI allows a comprehensive assessment of AS patients to guide treatment, evaluate prognosis and follow therapeutic responses.
Abstract Background Fever is one of the main symptoms for post-embolism syndrome (PES). This study aimed to determine and validate a model to predict fever after transcatheter arterial chemoembolization (TACE) in patients receiving platinum as the main regimen. Materials and Methods Clinical data of HCC patients who underwent TACE with platinum was retrospectively collected in the Fudan University Zhongshan Hospital during January 2016 to January 2018. According to post-TACE medical records, patients were divided into fever group and non-fever group. Predictive factors were selected by multivariate logistic regression. The receiver operating characteristic (ROC) curve were then performed to detect accuracy and discriminative ability of these factors using the derivation cohort and an independent validation cohort. Results Fevers were detected in 44 of 252 patients. Demographics, laboratory data were statistically similar within fever group and non-fever group. Strongest predictors identified in multivariate logistic regression included Iopiodol emulsion dose (OR, 1.081; 95%CI, 1.006-1.162), number of hepatoprotectants (OR, 0.619; 95%CI, 0.419-0.914), K + (OR, 2.992; 95%CI, 1.225-7.308), and albumin-bilirubin (ALBI) grade (OR, 2.249; 95%CI, 1.040-4.862). Furthermore, the area under the ROC curve of derivation cohort and validation cohort were 0.798 and 0.874 respectively, which indicated comparative stability and discriminative ability of this model. Conclusions Iopiodol emulsion dose, number of hepatoprotectants, K + , and ALBI grade are strong predictors for PEF. The multivariate logistic model of these factors shows a discriminative ability to predict PEF in the validation cohort.
The purpose of this study was to evaluate the role of bidirectional arterial flow combined with ultrasound elastography for differentiation of American College of Radiology Breast Imaging Reporting and Data System (BI-RADS) category 4 masses.A total of 116 BI-RADS category 4 breast masses were evaluated with color Doppler sonography, spectral analysis, and elastography. The sensitivity, specificity, accuracy, positive and negative predictive values, and receiver operator characteristic curve were used to estimate the diagnostic performance for each modality and the combination method.The combination method had the best sensitivity (81.1%) but less specificity (94.9%) and the best accuracy (90.5%). The discriminating power of the combined method (area under the curve [AUC], 0.880; 95% confidence interval [CI], 80.0%-96.0%) was significantly higher than that of bidirectional arterial flow (AUC, 0.818; 95% CI, 72.0%-91.6%; P< .01) and elastography (AUC, 0.765; 95% CI, 65.9%-87.0%; P< .01).Bidirectional arterial flow evaluation, when combined with elastography, could potentially improve diagnostic accuracy for BI-RADS category 4 breast masses.
To explore the application value of Revolution CT combining three -dimensional visualization technique in the precision resection of hepatic alveolar echinococcosis.Totally 12 patients with surgical treatment and pathologically confirmed hepatic alveolar echinococcosis in Qinghai Provincial People's Hospital were retrospectively analyzed. All the patients underwent the Revolution CT plain and enhancement scan before surgery, and the 0.625 millimeter scan data were obtained. The DICOM format data were imported into MI-3DVS for three-dimensional reconstruction, simulated cutting, volume measurement, and surgical planning.The data of 12 patients were reconstructed successfully, and the sizes and locations of the lesions as well as the hepatic vascular systems were clearly displayed. The liver volume, hydatid volume, simulated resection volume, and residual liver ratio were measured accurately. The average whole liver volume and the lesion volume of the 11 surgical treated patients were (2 429.8 ± 335.9) mL and (919.6 ± 262.8) mL respectively. The average actually removed volume was highly associated with the average simulated resection volume (r = 0.979, P < 0.01).Revolution CT combining three-dimensional visualization technique can achieve accurate diagnosis as well as optimal surgical planning before operation, which is of great value for the precision resection of difficult hepatic alveolar echinococcosis.［摘要］目的 探究 Revolution CT 结合三维可视化技术在指导肝棘球蚴病精准切除术中的应用价值。方法 回顾性分析青海省人民医院 12 例经手术治疗的多房棘球蚴病患者临床资料, 所有患者术前均接受 Revolution CT 上腹平扫+增强检查, 将 DICOM 格式的 0.625 mm 扫描数据导入人体三维可视化软件 (MI-3DVS) 进行三维重建、模拟切割、体积测量并制定手术规划。结果 12 例患者均完成了三维可视化模型重建, 棘球蚴病病灶大小、所在肝段及肝内血管系统均显示清晰, 并准确测得全肝体积、棘球蚴病病灶体积、模拟切除体积和残肝比。11 例手术患者平均全肝体积为 (2429.8±335.9) mL, 平均棘球蚴病病灶体积为 (919.6 ± 262.8) mL, 实际切除病灶体积与模拟切除病灶体积具有高度相关性 (r = 0.979, P < 0.01)。结论 Revolution CT 结合三维可视化技术能实现术前准确诊断并制定最佳手术规划, 对指导难度较大的肝多房棘球蚴病精准切除术具有重要价值。.
Inactivation of the tumor suppressor Ras-association domain family 1 isoform A (RASSF1A) due to epigenetic silencing occurs in a variety of human cancers, and still largely unknown are the regulators and mechanisms underlying RASSF1A gene promoter methylation. Herein, we report that this methylation is regulated by p53 and death-associated protein 6 (DAXX) in acute lymphoblastic leukemia (ALL). We found that p53 bound to the RASSF1A promoter, recruiting DAXX as well as DNA methyltransferase 1 (DNMT1) for DNA methylation, which subsequently resulted in inactivation of RASSF1A in wild-type p53 ALL cells. Although the presence of p53 was required for the recruitment of DAXX and DNMT1 to the RASSF1A promoter, fluctuation in p53 protein levels did not affect the rates of RASSF1A methylation. Conversely, methylation of RASSF1A promoter was critically controlled by DAXX, as the enforced overexpression of DAXX led to enhanced RASSF1A promoter methylation, whereas inhibition of DAXX reduced RASSF1A methylation. Interestingly, we found that the p53/DAXX-mediated RASSF1A methylation regulated murine double minute 2 (MDM2) protein stability in ALL. Our results reveal a novel function for p53 in the methylation of RASSF1A promoter by its interaction with DAXX. Discovery of this mechanism provides new insight into the interactions among the tumor-related factors p53, RASSF1A, DAXX, and MDM2 in cancer pathogenesis.—Zhang, H., He, J., Li, J., Tian, D., Gu, L., Zhou, M. Methylation of RASSF1A gene promoter is regulated by p53 and DAXX. FASEB J. 27, 232–242 (2013). www.fasebj.org
Besides the study on examining facet joints of lumbar spine by ultrasound in normal population, there has not been any related report about examining normal facet joints of lumbar spine by ultrasound so far. This study was aimed to explore the feasibility of ultrasound assessment of lumber spine facet joints by comparing ultrasound measure values of normal and degenerative lumber spine facet joints, and by comparing measure values of ultrasound and computed tomography (CT) of degenerative lumber spine facet joints. This study included 15 patients who had chronic low back pain because of degenerative change in lumbar vertebrae, and 19 volunteers who did not have low back pain or pain in the lower limb. The ultrasound measure values (height [H] and width [W]) of normal and degenerative lumber spine facet joints were compared. And the differentiation between measure values (H and W) of ultrasound and CT of degenerative lumber spine facet joints was also analyzed. The ultrasound clearly showed abnormal facet joints lesion, which was characterized by hyperostosis on the edge of joints, bone destruction under joints, and thinner or thicker articular cartilage. There were significant differences between the ultrasound measure values of the normal (H: 1.26 ± 0.03 cm, W: 0.18 ± 0.01 cm) and abnormal facet joints (H: 1.43 ± 0.05 cm, W: 0.15 ± 0.02 cm) (all P < .05). However, there were no significant differences between the measure values of the ultrasound (H: 1.43 ± 0.17 cm, W: 0.15 ± 0.03 cm) and CT (H: 1.42 ± 0.16, W: 0.14 ± 0.03) of the degenerative lumber spine facet joints (all P > .05). Ultrasound can clearly show the structure of facet joints of lumbar spine. It is precise and feasible to assess facet joints of lumbar spine by ultrasound. This study has important significance for the diagnosis of lumbar facet joint degeneration.
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