Xiaofeng Tao

Expression of angiopoietin-2 and vascular endothelial growth factor receptor-3 correlates with lymphangiogenesis and angiogenesis and affects survival of oral squamous cell carcinoma

Background Both Ang-2 and VEGFR-3 are major regulators of angiogenesis and lymphangiogenesis, respectively, and thus may affect prognosis of OSCC. We sought to determine the associations between Ang-2 and VEGFR-3 expression and survival of OSCC. Methods Ang-2 and VEGFR-3 expression was determined immunohistochemically in tumor tissues from 112 patients with OSCC; OSCC-adjacent noncancerous oral tissue from 85 OSCC patients; and normal oral mucosa from 37 cancer-free individuals. A log-rank test and Cox proportional hazard models were used to compare survival among different groups with expression of Ang-2 and VEGFR-3. Results Ang-2 and VEGFR-3 expression was upregulated in OSCC compared to nontumor tissue (all P<0.05). High Ang-2 expression positively correlated with microvessel density (MVD) (P<0.01), and high VEGFR-3 expression positively correlated with lymph node metastasis (P<0.01) and lymphatic vessel density (LVD) (P<0.01). The patients with high expression of Ang-2 alone or in combination with VEGFR-3 had a significantly worse survival than in patients with low expression of Ang-2 or any other co-expression status (all P<0.05), respectively. Furthermore, multivariable analysis showed that patients with high expression of Ang-2 alone or in combination with VEGFR-3 had a significantly increased risk of death compared with those with low expression of Ang-2 or any other co-expression status (HR, 2.7, 95% CI, 1.1–6.2 and 5.0, 1.3–15.4, respectively). Conclusions These results suggest that increased expression in tumors of Ang-2 may individually, or in combination with VEGFR-3, predict poor prognosis of OSCC.

Inflammatory Bowel Disease: MR- and SPECT/CT-based Macrophage Imaging for Monitoring and Evaluating Disease Activity in Experimental Mouse Model—Pilot Study

PURPOSE To evaluate the feasibility of using magnetic resonance (MR) imaging and single photon emission computed tomography (SPECT)/computed tomography (CT) to visualize the in vivo recruitment of iron oxide-labeled macrophages and indium 111 ((111)In)-labeled macrophages in inflammatory bowel disease (IBD) and to monitor disease activity. MATERIALS AND METHODS This study had institutional animal care and use committee approval. Twenty-seven C57/B6 mice with dextran sodium sulfate (DSS)-induced IBD and control mice were included. Peritoneal macrophages were harvested from seven thioglycollate-treated mice and were labeled with superparamagnetic iron oxide (SPIO) nanoparticles. Macrophage iron content was determined by using inductively coupled plasma mass spectrometry. SPIO nanoparticle-labeled macrophages (5 × 10(6)) were intravenously administered. Mice with DSS-induced IBD (n = 8) and control mice (n = 6) were imaged with a 9.4-T MR imaging unit at 0, 5, and 24 hours after macrophage administration. Percentage normalized enhancement (NE) was calculated for the intestinal wall and liver 24 hours after injection. Six mice with IBD coinjected with SPIO nanoparticles and (111)In oxine-labeled macrophages were imaged with MR imaging and SPECT/CT after 24 hours. The pharmacokinetics and biodistribution of the implanted macrophages were determined. Correlation between percentage NE and IBD scores was calculated. RESULTS Ex vivo mass spectrometry revealed strong SPIO nanoparticle uptake (7.4 pg iron per cell). R2* correlated with cell number (r = 0.9813, P < .05). Percentage NE correlated with both clinical (r = 0.924) and pathologic (r = 0.795) IBD score. Cell circulation half-life in the first and second phases was 0.32 hour and 10.2 hours, respectively. SPECT/CT showed that approximately 3% of the injected dose was present in the intestines 24 hours after injection; this was confirmed at MR imaging and histologic examination. Indium 111-labeled cells were present in all tissue associated with the reticuloendothelial system or mononuclear phagocyte system at 24 hours. CONCLUSION SPIO nanoparticles and (111)In-labeled macrophages could be observed in vivo at MR imaging and SPECT/CT in mice with IBD. Percentage NE at MR imaging correlates with disease activity.

Treatment and Prognosis of Anaplastic Thyroid Carcinoma: Experience from a Single Institution in China

Background Anaplastic thyroid carcinoma (ATC), a highly aggressive malignancy, has a poor prognosis, and the consensus on the most effective treatment is needed. Methods Clinical data from all ATC patients treated in our institution over a 30-year period (between May 1980 and May 2010) were analyzed retrospectively with regard to mortality and survival rates (Kaplan–Meier). Multivariate analysis was performed using a Cox proportional hazards model. Results Sixty cases were analyzed. The overall 1- and 3-year survival rates were 35.0% and 22.9%, respectively. Univariate analysis showed that the best prognosis was seen in patients younger than 55 years, those without distant metastases, those with white blood cell (WBC) counts < 10.0 × 109/L or blood platelet (PLT) counts < 300.0 × 109/L at presentation, those who did not receive chemotherapy, and those who received radiotherapy doses ≥ 40 Gy or underwent surgery plus postoperative radiotherapy. According to multivariate analysis, the WBC count at first presentation and the type of therapeutic regimen independently influenced survival. Conclusions We found that the elevated peripheral PLT count may be an adverse prognostic factor of ATC patients. The prognosis for ATC is especially poor for patients with distant metastasis, a WBC count ≥ 10.0×109/L, a PLT count ≥ 300.0 × 109/L, or age ≥ 55 years. WBC count at presentation and surgery with or without postoperative radiotherapy independently influenced the prognosis. Intensive treatment combining surgery with postoperative radiotherapy is recommended for ATC patients with stage IVA/B disease.

MicroRNA signatures predict prognosis of patients with glioblastoma multiforme through the Cancer Genome Atlas

MicroRNAs (miRNAs) play major roles in various biological processes and have been implicated in the pathogenesis and malignant progression of glioblastoma multiforme (GBM). The aim of this study was to assess the predictive values of miRNAs for overall survival (OS) of patients with GBM. MiRNA expression profiles and clinical information of 563 GBM patients were obtained from the Cancer Genome Atlas. The most significantly altered miRNAs were identified and miRNA expression profiles were performed, through principal component analysis, the least absolute shrinkage and selection operator method. The survival analysis was performed using the Cox regression models. Additionally, receiver operating characteristic (ROC) analysis was used to assess the performance of survival prediction. We used the bioinformatics tools to establish the miRNA signature for biological relevance assessment. A linear prognostic model of three miRNAs was developed and the patients were divided into high risk and low risk groups based this model. The area under the ROC curve (AUC) for the three miRNA signature predicting 5-year survival was 0.894 (95%CI, 0.789-1.000) in the testing set and0.841 (95%CI, 0.689-0.993) in all GBM patients. High risk patients had significantly shorter OS than patients with low risk (P< 0.001). The results from this study support a three miRNA signature for outcome prediction of GBM. These results provided a new prospect for prognostic biomarker of GBM.MicroRNAs (miRNAs) play major roles in various biological processes and have been implicated in the pathogenesis and malignant progression of glioblastoma multiforme (GBM). The aim of this study was to assess the predictive values of miRNAs for overall survival (OS) of patients with GBM. MiRNA expression profiles and clinical information of 563 GBM patients were obtained from the Cancer Genome Atlas. The most significantly altered miRNAs were identified and miRNA expression profiles were performed, through principal component analysis, the least absolute shrinkage and selection operator method. The survival analysis was performed using the Cox regression models. Additionally, receiver operating characteristic (ROC) analysis was used to assess the performance of survival prediction. We used the bioinformatics tools to establish the miRNA signature for biological relevance assessment. A linear prognostic model of three miRNAs was developed and the patients were divided into high risk and low risk groups based this model. The area under the ROC curve (AUC) for the three miRNA signature predicting 5-year survival was 0.894 (95%CI, 0.789-1.000) in the testing set and0.841 (95%CI, 0.689-0.993) in all GBM patients. High risk patients had significantly shorter OS than patients with low risk (P< 0.001). The results from this study support a three miRNA signature for outcome prediction of GBM. These results provided a new prospect for prognostic biomarker of GBM.

Oxygen-enhanced magnetic resonance imaging of the brain: a rodent model.

&NA; Oxygen‐enhanced MRI has been shown to be a viable alternative to hyperpolarized gases for pulmonary imaging. The changes in the relaxation times due to hyperoxic conditions in the blood pool induced by inhalation of pure oxygen have produced sufficient signal changes for imaging applications. This is a safe and low‐cost alternative for contrast‐enhanced imaging. The application of oxygen‐enhanced MRI in brain imaging has been much less studied. In this study, we investigated the changes in the relaxation times in the brain due to inhalation of pure oxygen in a rodent model. We also assessed the effects of reduced blood flow due to hyperoxic conditions. Despite the reduced blood flow, significant changes in T1, T2, and T2* relaxation times were detected. We conclude that oxygen‐enhanced MRI can be used in rodent models of disease.

Thyroid functional parameters and correlative autoantibodies as prognostic factors for differentiated thyroid cancers

To evaluate the effect of preoperative thyroid functional parameters and thyroid autoantibodies on aggressive clinicopathologic features and lymph node metastasis (LNM) of differentiated thyroid cancer patients. Four hundred twenty consecutive patients with initial surgery were enrolled from July 2010 to July 2015. The associations between aggressive clinicopathologic and LNM factors and thyroid functional & autoantibodies parameters were analyzed. Higher levels of TSH, TGAb or TMAb were found in patients with tumor size≥1 cm (all P<0.05), especially when TSH≥2.5 ulU/ml (P=0.03) and TGAb≥1 (P=0.01). Higher levels of TSH and TGAb and lower levels of T3 and T4 were found in patients with capsular invasion (all P<0.05), particularly when TSH≥2.5ulU/ml (P=0.03) and TGAb≥1 (P=0.005). The patients with multifocality had higher TAbs level (TAbs>1). Higher level of TSH was also found in patients with central LNM (P=0.001) and lateral LNM (P=0.002), especially with TSH≥2.5ulU/ml (P=0.003 and P=0.03). TGAb level was also found higher in patients with central LNM (P=0.02) and lateral LNM (P=0.01), especially with TGAb≥1 (P<0.05 and P=0.01). Higher level of TMAb was found in patients with lateral LNM (P<0.05). Moreover, multivariable analysis revealed that only TGAb was an independently predictive factor for primary tumor size≥1cm (P=0.01); and TSH level (P=0.01) and TGAb≥1 (P<0.05) were associated independently with central LNM. Thus, TSH level and TGAb≥1 were significantly independent predictors for central LNM, and might help make the decision of central neck dissection.

Differentiation of orbital lymphoma and idiopathic orbital inflammatory pseudotumor: combined diagnostic value of conventional MRI and histogram analysis of ADC maps

BackgroundThe overlap of morphological feature and mean ADC value restricted clinical application of MRI in the differential diagnosis of orbital lymphoma and idiopathic orbital inflammatory pseudotumor (IOIP). In this paper, we aimed to retrospectively evaluate the combined diagnostic value of conventional magnetic resonance imaging (MRI) and whole-tumor histogram analysis of apparent diffusion coefficient (ADC) maps in the differentiation of the two lesions.MethodsIn total, 18 patients with orbital lymphoma and 22 patients with IOIP were included, who underwent both conventional MRI and diffusion weighted imaging before treatment. Conventional MRI features and histogram parameters derived from ADC maps, including mean ADC (ADCmean), median ADC (ADCmedian), skewness, kurtosis, 10th, 25th, 75th and 90th percentiles of ADC (ADC10, ADC25, ADC75, ADC90) were evaluated and compared between orbital lymphoma and IOIP. Multivariate logistic regression analysis was used to identify the most valuable variables for discriminating. Differential model was built upon the selected variables and receiver operating characteristic (ROC) analysis was also performed to determine the differential ability of the model.ResultsMultivariate logistic regression showed ADC10 (P = 0.023) and involvement of orbit preseptal space (P = 0.029) were the most promising indexes in the discrimination of orbital lymphoma and IOIP. The logistic model defined by ADC10 and involvement of orbit preseptal space was built, which achieved an AUC of 0.939, with sensitivity of 77.30% and specificity of 94.40%.ConclusionsConventional MRI feature of involvement of orbit preseptal space and ADC histogram parameter of ADC10 are valuable in differential diagnosis of orbital lymphoma and IOIP.

Investigation of hypoxia conditions using oxygen-enhanced magnetic resonance imaging measurements in glioma models

The objective of this study was to determine whether using oxygen-enhanced magnetic resonance imaging (OE-MRI) to assess hypoxia is feasible and whether historical measurements, pO2 changes, and percentage of signal intensity changes (PSIC) are correlated in an animal model of glioma. A total of 25 Sprague-Dawley rats were used to establish C6 brain or subcutaneous glioma model. Nine rats with brain gliomas underwent OE-MRI followed by histopathologic analysis to assess microvessel density and hypoxia. Another 11 rats were underwent OE-MRI and were followed for a survival analysis. Time–T1-weighted MR signal intensity (SI) curves and PSIC maps were derived from the OE-MRI data. High–regions of interests (ROI-h; PSIC > 10%) and low-ROIs (ROI-l; PSIC < 10%) were defined on the PSIC maps. To validate the PSIC map for identifying tumor hypoxia, we subjected an additional 5 rats with subcutaneous glioma to OE-MRI and pO2 measurements. All tumors showed regional heterogeneity on the PSIC maps. For the brain tumors, the time-SI curves for the ROIs-h showed a greater increase in SI than those for the ROIs-l did. The percentage of tumor area with a low PSIC was significantly correlated with the percentage of hypoxia staining and necrosis (r =0.71; P<0.05). ROIs with a higher PSIC typically had more vessels (r=0.88; P<0.05). A significant difference in survival was shown (log-rank P = 0.035). The time-pO2 curves of the subcutaneous tumors were similar to the time-SI curves. PSIC was significantly correlated with pO2 changes (r =0.82; P<0.05). These findings suggest that OE-MRI measurements can be used to assess hypoxia in C6 glioma models. In these models, the PSIC value was correlated with survival, indicating that PSIC could serve as a prognostic marker for glioma.

Effects of hyperoxia on resting state functional magnetic resonance imaging.

We studied the effect of oxygen inhalation during resting state functional MRI scanning in healthy control individuals. We hypothesized that resting state networks would be modified under hyperoxic conditions. Thirty-four normal volunteers were recruited for this study. All participants were scanned twice: once while breathing atmospheric air and once under hyperoxic conditions in a randomized order. Hyperoxic conditions were produced by administering 100% O2. Blood oxygen level-dependent T2* scans were obtained for each of the scans. Resting state networks were extracted using independent component analysis. A paired t-test showed that the resting state networks scans (default mode network, attention network and executive network) acquired under hyperoxic conditions had significantly higher Z-scores than scans performed under atmospheric air. Spectral analysis of the time-course signal in these networks also showed a difference in the total power of low frequencies between the two conditions. These results were reversed in the visual network. Clinical or research applications of oxygen-enhanced MRI need to take into account the modularly effects that hyperoxia exerts on the networks resting state functional MRI.

Magnetic resonance imaging based radiomics signature for the preoperative discrimination of stage I-II and III-IV head and neck squamous cell carcinoma

PURPOSE This study aimed to investigate the predictive ability of magnetic resonance imaging (MRI) based radiomics signature for the preoperative staging in HNSCC. METHODS This study involved127 consecutive patients (training cohort: n = 85; testing cohort, n = 42) with stage I-IV HNSCC. A total of 970 radiomics features were extracted from T2-weighted (T2W) (n = 485) and contrast-enhanced T1-weighted (ceT1W) (n = 485) MRI for each case. Radiomics signatures were constructed with least absolute shrinkage and selection operator (LASSO) logistic regression. Associations between radiomics signatures and HNSCC staging were explored. Areas under the receiver operating characteristic curve (AUC) and classification performance of radiomics signatures were determined and compared with those of the visual assessment. RESULTS Ten features from T2W images, six from ceT1W images, and six from combined T2W and ceT1W images were selected by LASSO logistic regression. The three radiomics signatures of stage III-IV HNSCC were significantly higher than that for stage I-II in both cohorts (all P < 0.05). The radiomics signatures from ceT1W and combined images performed well in the discrimination of stage I-II and III-IV HNSCC, with AUCs of 0.828 and 0.850 in the training cohort, and AUCs of 0.853 and 0.849 in the testing cohort. Based on the cut-off value of the training cohort, the radiomics signature from combined images achieved best classification performance in both cohorts, with accuracies of 0.788 and 0.857, sensitivities of 0.836 and 0.885, and specificities of 0.700 and 0.813. Significant differences in accuracy and sensitivity were found between the radiomics signature from combined images and the visual assessment of the radiologists in the training cohort. CONCLUSION Radiomics signature based on MRI could discriminate stage I-II from stage III-IV HNSCC, which may serve as a complementary tool for preoperative staging.