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Endothelial progenitor cells (EPCs) play an important role in repairing ischemia tissues. Diffusion tensor imaging (DTI) was applied to detect the architectural organization of skeletal muscle. This study investigated the feasibility and accuracy of using the DTI to evaluate effectiveness of EPCs treatment. Mouse bone marrow-derived EPCs were isolated, cultured, characterized, and transplanted to hindlimb ischemia mice model. DTI was performed on the hindlimb at postischemia time points. The edema regions of diffusion restriction (high signal in diffusion weighted imaging) were decreased in the ischemic muscle of EPCs treated mice after 14 days compared with the controls. These results from DTI show the lower apparent diffusion coefficient and eigenvalues (λ1, λ2, and λ3) and the higher fractional anisotropy and fiber counts of ischemic muscle on 7 and 14 days after EPCs treatment compared to the controls. There was a significant correlation between fiber counts calculated by DTI and survival fibers evaluated by histological section (r=0.873, P<0.01). Our study demonstrated that the time frame for muscle fiber regeneration after EPCs transplantation was significantly shortened in vivo. DTI could be a useful tool for noninvasive evaluation of muscle tissue damage and repair in animal models and patient with ischemic diseases. [ABSTRACT FROM AUTHOR]

Aims We tested the hypothesis that endothelial progenitor cell ( EPC)-mediated functional recovery after stroke may be associated with the endothelial nitric oxide synthase (eNOS)/brain-derived neurotrophic factor ( BDNF) signaling pathway. Methods Mice were infused with either EPCs or saline after being subjected to middle cerebral artery occlusion. The EPC-treated mice also received intravenous injections of either Nω-nitro- l-arginine methyl ester (L- NAME, the NOS inhibitor) or saline. Results The activation of eNOS and the expression of BDNF were significantly increased in ischemic brain of the EPC-treated mice, along with increased angiogenesis and neurogenesis. On diffusion tensor imaging ( DTI), significant increases in fractional anisotropy and fiber count were observed in white matter, indicating axonal growth stimulated by EPCs. However, the EPC-treated mice that were received an L- NAME injection failed to exhibit the observed increases in angiogenesis, neurogenesis, and axonal growth. In addition, the neurons cocultured with EPCs in vitro exhibited the increased expression of BDNF and decreased apoptosis after oxygen-glucose deprivation compared with the control group. This EPC-induced protective effect was virtually absent in the L- NAME treatment group. Conclusion The eNOS/ BDNF pathway may be involved in the EPC-mediated functional recovery of stroke mice. DTI is feasible for dynamically tracking the orientation of axonal projections after EPC treatment. [ABSTRACT FROM AUTHOR]

Objectives: This study aims to investigate and develop imaging biomarkers for the diagnosis of cancer-associated cachexia based on the organ and tissue-specific abnormal metabolisms measured by fluorine-18-fluorodeoxyglucose (18F-FDG) PET/CT. Methods: FDG PET/CT data from 390 cancer patients were analyzed retrospectively. Patients were divided into a development cohort and a validation cohort. Cachexia was defined as weight loss > 5% in 6 months or BMI < 20 and weight loss > 2%. According to the above definitions, patients were divided into cachexia and non-cachexia groups. Results of the clinical laboratory tests for metabolic levels and organ and tissue-specific FDG uptake obtained from the cachexia and non-cachexia groups were compared statistically. Logistic regression analysis was performed to identify independent variables associated with cachexia in the development cohort for generating the regression model. The performance of the model was tested using the data from a validation cohort and evaluated by area under the receiver operating characteristic curve (AUC). Results: Based on the data from the development cohort of 286 patients and a validation cohort of 104 patients, it is found that age, white blood cell count, peak standardized uptake value (SUV) of the liver, and minimum SUV of lean body mass of visceral fat and subcutaneous fat were independently associated with cachexia. The model incorporating these variables reached an AUC of 0.777 (95% confidence interval (CI): 0.721, 0.833) in the development cohort and an AUC of 0.729 (95% CI: 0.629, 0.829) in the validation cohort. Conclusion: Organ and tissue-specific abnormal glucose metabolism as measured by PET/CT can be used as a biomarker for cancer-associated cachexia. Key Points: • Patients with cancer-associated cachexia have reduced FDG uptake in the liver and increased FDG uptake in visceral fat and subcutaneous fat. • FDG uptake of the liver, visceral fat, and subcutaneous fat can be independent risk factors for identifying cancer-associated cachexia. • Cancer-associated cachexia can be classified using the model that incorporates age, white blood cell count, FDG uptake of the liver, and visceral and subcutaneous fat can diagnose with an AUC of 0.729. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to assess the predictive efficacy of intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in parametrial invasion (PMI) in cervical cancer patients.A total of 83 cervical cancer patients (32 PMI-positive and 51 PMI-negative) retrospectively underwent pretreatment IVIM-DWI and DCE-MRI scans. IVIM-DWI parameters included apparent diffusion coefficient (ADC), slow apparent diffusion coefficient (D), fast apparent diffusion coefficient (D*), and perfusion fraction (f). DCE-MRI parameters included volume transfer constant (Ktrans), flux rate constant (Kep), and fractional extravascular extracellular space volume (Ve). Logistic regression analyses were conducted to identify independent variables associated with PMI. Receiver operating characteristic curves were generated to assess the predictive performance of significant parameters.Multivariable analysis revealed that the MRI parameters D (odds ratio [OR]: 7.05; 95% CI 1.78–27.88; P = 0.005), D* (OR 6.58; 95% CI 1.49–29.10; P = 0.01), f (OR 5.12; 95% CI 1.23–21.37; P = 0.03), Ktrans (OR 4.60; 95% CI 1.19–17.81; P = 0.03), and Kep (OR 4.90; 95% CI 1.25–19.18; P = 0.02) were independent predictors of PMI in cervical cancer patients. The combined parameter incorporating these parameters demonstrated the highest performance in predicting PMI, yielding an area under the curve of 0.906, sensitivity of 84.4%, and specificity of 86.3%.The proposed combined parameter exhibited favorable performance in identifying PMI in cervical cancer patients.Methods: This study aimed to assess the predictive efficacy of intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in parametrial invasion (PMI) in cervical cancer patients.A total of 83 cervical cancer patients (32 PMI-positive and 51 PMI-negative) retrospectively underwent pretreatment IVIM-DWI and DCE-MRI scans. IVIM-DWI parameters included apparent diffusion coefficient (ADC), slow apparent diffusion coefficient (D), fast apparent diffusion coefficient (D*), and perfusion fraction (f). DCE-MRI parameters included volume transfer constant (Ktrans), flux rate constant (Kep), and fractional extravascular extracellular space volume (Ve). Logistic regression analyses were conducted to identify independent variables associated with PMI. Receiver operating characteristic curves were generated to assess the predictive performance of significant parameters.Multivariable analysis revealed that the MRI parameters D (odds ratio [OR]: 7.05; 95% CI 1.78–27.88; P = 0.005), D* (OR 6.58; 95% CI 1.49–29.10; P = 0.01), f (OR 5.12; 95% CI 1.23–21.37; P = 0.03), Ktrans (OR 4.60; 95% CI 1.19–17.81; P = 0.03), and Kep (OR 4.90; 95% CI 1.25–19.18; P = 0.02) were independent predictors of PMI in cervical cancer patients. The combined parameter incorporating these parameters demonstrated the highest performance in predicting PMI, yielding an area under the curve of 0.906, sensitivity of 84.4%, and specificity of 86.3%.The proposed combined parameter exhibited favorable performance in identifying PMI in cervical cancer patients.Results: This study aimed to assess the predictive efficacy of intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in parametrial invasion (PMI) in cervical cancer patients.A total of 83 cervical cancer patients (32 PMI-positive and 51 PMI-negative) retrospectively underwent pretreatment IVIM-DWI and DCE-MRI scans. IVIM-DWI parameters included apparent diffusion coefficient (ADC), slow apparent diffusion coefficient (D), fast apparent diffusion coefficient (D*), and perfusion fraction (f). DCE-MRI parameters included volume transfer constant (Ktrans), flux rate constant (Kep), and fractional extravascular extracellular space volume (Ve). Logistic regression analyses were conducted to identify independent variables associated with PMI. Receiver operating characteristic curves were generated to assess the predictive performance of significant parameters.Multivariable analysis revealed that the MRI parameters D (odds ratio [OR]: 7.05; 95% CI 1.78–27.88; P = 0.005), D* (OR 6.58; 95% CI 1.49–29.10; P = 0.01), f (OR 5.12; 95% CI 1.23–21.37; P = 0.03), Ktrans (OR 4.60; 95% CI 1.19–17.81; P = 0.03), and Kep (OR 4.90; 95% CI 1.25–19.18; P = 0.02) were independent predictors of PMI in cervical cancer patients. The combined parameter incorporating these parameters demonstrated the highest performance in predicting PMI, yielding an area under the curve of 0.906, sensitivity of 84.4%, and specificity of 86.3%.The proposed combined parameter exhibited favorable performance in identifying PMI in cervical cancer patients.Conclusion: This study aimed to assess the predictive efficacy of intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in parametrial invasion (PMI) in cervical cancer patients.A total of 83 cervical cancer patients (32 PMI-positive and 51 PMI-negative) retrospectively underwent pretreatment IVIM-DWI and DCE-MRI scans. IVIM-DWI parameters included apparent diffusion coefficient (ADC), slow apparent diffusion coefficient (D), fast apparent diffusion coefficient (D*), and perfusion fraction (f). DCE-MRI parameters included volume transfer constant (Ktrans), flux rate constant (Kep), and fractional extravascular extracellular space volume (Ve). Logistic regression analyses were conducted to identify independent variables associated with PMI. Receiver operating characteristic curves were generated to assess the predictive performance of significant parameters.Multivariable analysis revealed that the MRI parameters D (odds ratio [OR]: 7.05; 95% CI 1.78–27.88; P = 0.005), D* (OR 6.58; 95% CI 1.49–29.10; P = 0.01), f (OR 5.12; 95% CI 1.23–21.37; P = 0.03), Ktrans (OR 4.60; 95% CI 1.19–17.81; P = 0.03), and Kep (OR 4.90; 95% CI 1.25–19.18; P = 0.02) were independent predictors of PMI in cervical cancer patients. The combined parameter incorporating these parameters demonstrated the highest performance in predicting PMI, yielding an area under the curve of 0.906, sensitivity of 84.4%, and specificity of 86.3%.The proposed combined parameter exhibited favorable performance in identifying PMI in cervical cancer patients.Graphical abstract: This study aimed to assess the predictive efficacy of intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in parametrial invasion (PMI) in cervical cancer patients.A total of 83 cervical cancer patients (32 PMI-positive and 51 PMI-negative) retrospectively underwent pretreatment IVIM-DWI and DCE-MRI scans. IVIM-DWI parameters included apparent diffusion coefficient (ADC), slow apparent diffusion coefficient (D), fast apparent diffusion coefficient (D*), and perfusion fraction (f). DCE-MRI parameters included volume transfer constant (Ktrans), flux rate constant (Kep), and fractional extravascular extracellular space volume (Ve). Logistic regression analyses were conducted to identify independent variables associated with PMI. Receiver operating characteristic curves were generated to assess the predictive performance of significant parameters.Multivariable analysis revealed that the MRI parameters D (odds ratio [OR]: 7.05; 95% CI 1.78–27.88; P = 0.005), D* (OR 6.58; 95% CI 1.49–29.10; P = 0.01), f (OR 5.12; 95% CI 1.23–21.37; P = 0.03), Ktrans (OR 4.60; 95% CI 1.19–17.81; P = 0.03), and Kep (OR 4.90; 95% CI 1.25–19.18; P = 0.02) were independent predictors of PMI in cervical cancer patients. The combined parameter incorporating these parameters demonstrated the highest performance in predicting PMI, yielding an area under the curve of 0.906, sensitivity of 84.4%, and specificity of 86.3%.The proposed combined parameter exhibited favorable performance in identifying PMI in cervical cancer patients. [ABSTRACT FROM AUTHOR]

BACKGROUND: Brain-metastatic breast cancer (BMBC) is increasing and poses a severe clinical problem because of the lack of effective treatments and because the underlying molecular mechanisms are largely unknown. Recent work has demonstrated that deregulation of epidermal growth factor receptor (EGFR) may correlate with BMBC progression. However, the exact contribution that EGFR makes to BMBC remains unclear. METHODS: The role of EGFR in BMBC was explored by serial analyses in a brain-trophic clone of human MDA-MB-231 breast carcinoma cells (231-BR cells). EGFR expression was inhibited by stable short-hairpin RNA transfection or by the kinase inhibitor erlotinib, and it was activated by heparin-binding epidermal growth factor-like growth factor (HB-EGF). Cell growth and invasion activities also were analyzed in vitro and in vivo. RESULTS: EGFR inhibition or activation strongly affected 231-BR cell migration/invasion activities as assessed by an adhesion assay, a wound-healing assay, a Boyden chamber invasion assay, and cytoskeleton staining. Also, EGFR inhibition significantly decreased brain metastases of 231-BR cells in vivo. Surprisingly, changes to EGFR expression affected cell proliferation activities less significantly as determined by a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, an anchorage-independent growth assay, and cell cycle analysis. Immunoblot analysis suggested that EGFR drives cells' invasiveness capability mainly through phosphoinositide 3-kinase/protein kinase B and phospholipase C γ downstream pathways. In addition, EGFR was involved less in proliferation because of the insensitivity of the downstream mitogen-activated protein kinase pathway. CONCLUSIONS: The current results indicated that EGFR plays more important roles in cell migration and invasion to the brain than in cell proliferation progression on 231-BR cells, providing new evidence of the potential value of EGFR inhibition in treating BMBC. Cancer 2012. © 2012 American Cancer Society. [ABSTRACT FROM AUTHOR]