-
[show abstract]
[hide abstract]
ABSTRACT: To improve time and accuracy in differentiating diffuse interstitial lung disease for computer-aided quantification, we introduce a hierarchical support vector machine which selects a class by training a binary classifier at each node in a hierarchy, thus allowing each classifier to use a class-specific quasi-optimal feature set. In addition, the computational cost-sensitive group-feature selection criterion combined with the sequential forward selection is applied in order to obtain a useful and computationally inexpensive quasi-optimal feature set for the purpose of accelerating the classification time. The classification time was reduced by up to 57% and the overall accuracy was significantly improved in comparison with the one-against-all and one-against-one support vector machine methods with sequential forward selection (paired t-test, p<0.001). The reduction of classification time as well as the improvement of overall accuracy demonstrates promise for the proposed classification method to be adopted in various real-time and on-line image-based clinical applications.
Computers in biology and medicine 11/2012; · 1.27 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Cimicifuga racemosa extracts have long been used to treat female reproductive disorders both in Asia and Europe. Here in this study, we examined the possible estrogen receptor (ER)alpha effects of Cimicifuga heracleifolia var. bifida ethanol extract (C-Ex), which has been used traditionally in Asia, in MCF-7 cells. The activity of C-Ex was characterized in a transient transfection system, using ERa and estrogen-responsive luciferase plasmids in HEK 293 cells and endogenous target genes were studied in MCF-7 cells. C-Ex failed to activate ERalpha and at a concentration of 0.005-0.5 mg/ml as examined by reporter activity. In addition, no statistically significant antiestrogenic activity was observed. However, to our interest, C-Ex enhanced expression of VEGF at 0.5 mg/ml concentration and repressed ERalpha both at the mRNA and protein levels in MCF-7 cells. These results suggested that C-Ex does not activate or inactivate ERalpha in a direct manner, but the extracts may affect factors in ER signal transduction pathway.
Pharmazie 11/2012; 67(11):947-50. · 1.01 Impact Factor
-
Bo-Kyeong Kang,
Eun Sil Yu,
Seung Soo Lee, Youngjoo Lee,
Namkug Kim,
Claude B Sirlin,
Eun Yoon Cho,
Suk Keu Yeom,
Jae Ho Byun,
Seong Ho Park,
Moon-Gyu Lee
[show abstract]
[hide abstract]
ABSTRACT: The aims of this study were to assess the confounding effects of hepatic iron deposition, inflammation, and fibrosis on hepatic steatosis (HS) evaluation by magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) and to assess the accuracies of MRI and MRS for HS evaluation, using histology as the reference standard.
In this institutional review board-approved prospective study, 56 patients gave informed consents and underwent chemical-shift MRI and MRS of the liver on a 1.5-T magnetic resonance scanner. To estimate MRI fat fraction (FF), 4 analysis methods were used (dual-echo, triple-echo, multiecho, and multi-interference), and MRS FF was calculated with T2 correction. Degrees of HS, iron deposition, inflammation, and fibrosis were analyzed in liver resection (n = 37) and biopsy (n = 19) specimens. The confounding effects of histology on fat quantification were assessed by multiple linear regression analysis. Using the histologic degree of HS as the reference standard, the accuracies of each method in estimating HS and diagnosing an HS of 5% or greater were determined by linear regression and receiver operating characteristic analyses.
Iron deposition significantly confounded estimations of FF by the dual-echo (P < 0.001) and triple-echo (P = 0.033) methods, whereas no histologic feature confounded the multiecho and multi-interference methods or MRS. The MRS (r = 0.95) showed the strongest correlation with histologic degree of HS, followed by the multiecho (r = 0.92), multi-interference (r = 0.91), triple-echo (r = 0.90), and dual-echo (r = 0.85) methods. For diagnosing HS, the areas under the curve tended to be higher for MRS (0.96) and the multiecho (0.95), multi-interference (0.95), and triple-echo (0.95) methods than for the dual-echo method (0.88) (P ≥ 0.13).
The multiecho and multi-interference MRI methods and MRS can accurately quantify hepatic fat, with coexisting histologic abnormalities having no confounding effects.
Investigative radiology 04/2012; 47(6):368-75. · 4.85 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Hypoxia and the androgen receptor (AR) play important roles in the development and progression of prostate cancer. In this study, the combined effects of dihydrotestosterone (DHT) and hypoxia on AR-mediated transactivation were investigated. Hypoxia alone did not induce a detectable ARE-mediated response in the absence of DHT. DHT-induced AR transcriptional activity was dramatically increased by hypoxia or ectopic expression of HIF-1α, as determined by introducing ARE-responsive reporter plasmids into LNCaP prostate cancer cells. The secretion of VEGF was enhanced by the combination of hypoxia and DHT as compared to each treatment alone. These effects were not due to increased expression of the AR or HIF-1α as a result of hypoxia and DHT treatment. These results provide evidence that hypoxia may stimulate as yet unknown factors, which further stimulate AR signal transduction pathways.
Biochemical and Biophysical Research Communications 02/2012; 418(2):319-23. · 2.48 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Lymph node (LN) status is an important parameter for determining the treatment strategy and for predicting the prognosis for patients with uterine cervical cancer. Computer-aided diagnosis (CAD) can be feasible for differentiating metastatic from non-metastatic lymph nodes in patients with uterine cervical cancer.
To determine the usefulness of CAD that comprehensively evaluates MR images and clinical findings for detecting LN metastasis in uterine cervical cancer.
In 680 LNs from 143 patients who underwent radical hysterectomy for uterine cervical cancer, the CAD system using the Bayesian classifier estimated the probability of metastasis based on MR findings and clinical findings. We compared the diagnostic accuracy for detecting metastatic LNs in the CAD and MR findings.
Metastasis was diagnosed in 70 (12%) LNs from 34 (24%) patients. The area under ROC curves of CAD (0.924) was greater than those of the mean ADC (0.854), minimum ADC (0.849), maximum ADC (0.827), short-axis diameter (0.856) and long-axis diameter (0.753) (P < 0.05). The specificity and accuracy of the CAD (86%, 86%) were greater than those of the mean ADC (77%, 77%), maximum ADC (77%, 77%), minimum ADC (68%, 70%), and short-axis diameter (65%, 67%) (P < 0.05).
CAD system can improve the diagnostic performance of MR for detecting metastatic LNs in uterine cervical cancer.
Acta Radiologica 12/2011; 52(10):1175-83. · 1.37 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: To know whether contrast-enhanced dual-energy computed tomography angiography (DECTA) can be used for simultaneous assessment of emphysema quantification and regional perfusion evaluation.
We assessed 27 patients who had pulmonary emphysema and no pulmonary embolism on visual assessment of CT images, among 584 consecutive patients who underwent DECTA for the evaluation of pulmonary embolism. Virtual noncontrast (VNC) images were generated by modifying the "Liver VNC" application in a dedicated workstation. Using in-house software, the low-attenuation area below 950HU (LAA950), the 15th percentile attenuation (15pctlVNC) and the mean lung attenuation (MeanVNC) were calculated. The "Lung PBV" application was used to assess perfusion, and the low-iodine area below 5HU (LIA5), the 15th percentile iodine (15pctlIodine), and the mean iodine value (MeanIodine) were calculated from iodine map images. The correlation between VNC parameters and pulmonary function test data (available in 22 patients) and the correlation between VNC and iodine map parameters (all included 27 patients) were assessed. Color-coded map of VNC image were compared with iodine map images for the evaluation of regional heterogeneity.
We observed moderate correlations between LAA950 and predicted %FEV1 (rs = -0.47, P < 0.05), and 15pctlVNC and predicted %FEV1 (rs = 0.56, P < 0.05). We also observed significant correlations between LAA950 and LIA5 (rs = 0.48, P < 0.05), 15pctlVNC and 15pctlIodine (rs = 0.59, P = 0.001), and MeanVNC and MeanIodine (rs = 0.47, P < 0.05). On visual assessment of the regional heterogeneity, 82% of patients showed relatively good correlation between the areas of perfusion impairment on iodine map images and areas of emphysema on color-coded VNC images.
We observed moderate correlations between quantitative parameters on VNC images and pulmonary function test data, and also observed moderate correlations between the severity of parenchymal destruction, as determined from VNC images, and perfusion status, as determined from iodine maps. Therefore, the contrast-enhanced DECTA can be used for the emphysema quantification and regional perfusion evaluation by using the VNC images and iodine map, simultaneously.
Investigative radiology 07/2011; 47(1):92-7. · 4.85 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: To compare the accuracy of four chemical shift magnetic resonance imaging (MRI) (CS-MRI) analysis methods and MR spectroscopy (MRS) with and without T2-correction in fat quantification in the presence of excess iron.
CS-MRI with six opposed- and in-phase acquisitions and MRS with five-echo acquisitions (TEs of 20, 30, 40, 50, 60 msec) were performed at 1.5 T on phantoms containing various fat fractions (FFs), on phantoms containing various iron concentrations, and in 18 patients with chronic liver disease. For CS-MRI, FFs were estimated with the dual-echo method, with two T2*-correction methods (triple- and multiecho), and with multiinterference methods that corrected for both T2* and spectral interference effects. For MRS, FF was estimated without T2-correction (single-echo MRS) and with T2-correction (multiecho MRS).
In the phantoms, T2*- or T2-correction methods for CS-MRI and MRS provided unbiased estimations of FFs (mean bias, -1.1% to 0.5%) regardless of iron concentration, whereas the dual-echo method (-5.5% to -8.4%) and single-echo MRS (12.1% to 37.3%) resulted in large biases in FFs. In patients, the FFs estimated with triple-echo (R = 0.98), multiecho (R = 0.99), and multiinterference (R = 0.99) methods had stronger correlations with multiecho MRS FFs than with the dual-echo method (R = 0.86; P ≤ 0.011). The FFs estimated with multiinterference method showed the closest agreement with multiecho MRS FFs (the 95% limit-of-agreement, -0.2 ± 1.1).
T2*- or T2-correction methods are effective in correcting the confounding effects of iron, enabling an accurate fat quantification throughout a wide range of iron concentrations. Spectral modeling of fat may further improve the accuracy of CS-MRI in fat quantification.
Journal of Magnetic Resonance Imaging 06/2011; 33(6):1390-8. · 2.70 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The effects of red ginseng extract on lipid metabolism were examined in ovariectomized rats. Twenty-four female Sprague-Dawley rats (210 +/- 20 g) were studied for 10 weeks. The rats were divided into four groups: (I) "sham" non-ovariectomized rats treated with olive oil, (II) control ovariectomized rats treated with olive oil, (III) ovariectomized rats treated with 0.5 mg/kg 17beta-estradiol in olive oil, and (IV) ovariectomized rats treated with 5mg/kg red ginseng extract in olive oil. Red ginseng extract induced significant reductions in total cholesterol, low density lipoprotein cholesterol/total cholesterol, high density lipoprotein cholesterol/total cholesterol, and low density lipoprotein cholesterol/high density lipoprotein cholesterol, implying the effectiveness of ginseng in targeting postmenopausal symptoms.
Pharmazie 06/2011; 66(6):450-3. · 1.01 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: As a model compound for the transcription factor hijacking mechanism of action of DNA damaging agent that simultaneously bind to the nuclear receptor, we designed and synthesized a chimeric molecule, RA-mustard, which can bind with both retinoic acid receptor α (RARα) and DNA. The interaction between RA-mustard with RARα was confirmed by binding assay using RARα-overexpressing cell extract. RA-mustard-modified DNA diminished the RARα-dependent luciferase expression in the RARα-abundant cells.
Bioorganic & medicinal chemistry letters 05/2011; 21(14):4248-51. · 2.65 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The estrogen receptor is one of the most important transcription factors in breast tumor growth and development. We, and others, have previously shown that hypoxia induces rapid ERα protein degradation by a proteasome-mediated pathway in breast cancer cells, which is linked with ERα activation. However, no report has shown the effect of hypoxia on ESR1 gene regulation at the transcriptional level. In this report, we show that hypoxia repressed the expression of ERα mRNA in MCF-7 and T47D human breast cancer cells, but not in human endometrial Ishikawa cells, although ERα degradation under hypoxia was also observed in Ishikawa cells. This indicates that ESR1 transcriptional repression and ERα protein downregulation by hypoxia are regulated by distinct mechanisms. Repression of ESR1 gene transcription occurred at the transcriptional level as a result of decreased recruitment of RNA polymerase II at the proximal promoter of the ESR1 locus in response to stabilization of the HIF-1α protein under hypoxia. Our data show that hypoxia induces repression of the ESR1 gene, which may facilitate hormone insensitivity in the tumor microenvironment.
Biochemical and Biophysical Research Communications 03/2011; 407(4):831-6. · 2.48 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Estrogen receptor (ER) β is predicted to play an important role in prevention of breast cancer development and metastasis. We have shown previously that ERβ inhibits hypoxia inducible factor (HIF)-1α mediated transcription, but the mechanism by which ERβ works to exert this effect is not understood.
Vascular endothelial growth factor (VEGF) was measured in conditioned medium by enzyme-linked immunosorbent assays. Reverse transcription polymerase chain reaction (RT-PCR), Western blotting, immunoprecipitation, luciferase assays and chromatin immunoprecipitation (ChIP) assays were used to ascertain the implication of ERβ on HIF-1 function.
In this study, we found that the inhibition of HIF-1 activity by ERβ expression was correlated with ERβ's ability to degrade aryl hydrocarbon receptor nuclear translocator (ARNT) via ubiquitination processes leading to the reduction of active HIF-1α/ARNT complexes. HIF-1 repression by ERβ was rescued by overexpression of ARNT as examined by hypoxia-responsive element (HRE)-driven luciferase assays. We show further that ERβ attenuated the hypoxic induction of VEGF mRNA by directly decreasing HIF-1α binding to the VEGF gene promoter.
These results show that ERβ suppresses HIF-1α-mediated transcription via ARNT down-regulation, which may account for the tumour suppressive function of ERβ.
Breast cancer research: BCR 03/2011; 13(2):R32. · 5.24 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Mammalian MST2 kinase plays an important role in cell proliferation, survival, and apoptosis. In search of interacting proteins of MST2, we found that estrogen receptor α (ERα) co-immunoprecipitates with MST2 and its adaptor protein human Salvador (hSAV). Using reporter assays, we observed that overexpression of MST2 and hSAV leads to ligand-independent activation of ERα in human breast cancer MCF-7 cells, which was attenuated by the knockdown of hSAV. Furthermore, using truncated mutants of hSAV, we observed that the C terminus of hSAV is necessary and sufficient for the induction of ERα transactivation. The expression of hSAV and MST2 results in the phosphorylation of ERα at serine residues 118 and 167 and represses ERα expression. We then investigated the incidence of MST2 and ERα expression with other tumor biomarkers using commercially available tissue microarrays. Among 40 breast cancer samples analyzed, 60% (24 out of 40) expressed MST2. Nineteen among the 40 cases were MST2-positive and ERα-negative, implying a correlation between expressions of MST2 with loss of ERα in breast tumor samples. This study suggests that MST and hSAV act as novel co-regulators of ERα and may play an important role in breast cancer pathogenesis.
Journal of Molecular Medicine 02/2011; 89(2):181-91. · 4.67 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: We propose the use of a context-sensitive support vector machine (csSVM) to enhance the performance of a conventional support vector machine (SVM) for identifying diffuse interstitial lung disease (DILD) in high-resolution computerized tomography (HRCT) images. Nine hundred rectangular regions of interest (ROIs), each 20 × 20 pixels in size and consisting of 150 ROIs representing six regional disease patterns (normal, ground-glass opacity, reticular opacity, honeycombing, emphysema, and consolidation), were marked by two experienced radiologists using consensus HRCT images of various DILD. Twenty-one textual and shape features were evaluated to characterize the ROIs. The csSVM classified an ROI by simultaneously using the decision value of each class and information from the neighboring ROIs, such as neighboring region feature distances and class differences. Sequential forward-selection was used to select the relevant features. To validate our results, we used 900 ROIs with fivefold cross-validation and 84 whole lung images categorized by a radiologist. The accuracy of the proposed method for ROI and whole lung classification (89.88 ± 0.02%, and 60.30 ± 13.95%, respectively) was significantly higher than that provided by the conventional SVM classifier (87.39 ± 0.02%, and 57.69 ± 13.31%, respectively; paired t test, p < 0.01, and p < 0.01, respectively). We conclude that our csSVM provides better overall quantification of DILD.
Journal of Digital Imaging 02/2011; 24(6):1133-40. · 1.25 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Two new and two known compounds were identified as estrogenic constituents from Broussonetia kazinoki. Their structures were elucidated as broussonin A (1), tupichinol C (2), kazinol U (3), and (+)-(2R) kazinol I (4). They showed estrogenic activity with ligand-binding activity of estrogen receptor, transcriptional activity of estrogen-responsive element-luciferase reporter genes. They also control the cellular gene expression levels of estrogen-responsive genes. Phytoestrogens from B. kazinoki may have beneficial effects in the treatment of menopausal symptoms.
Bioorganic & medicinal chemistry letters 06/2010; 20(12):3764-7. · 2.65 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The objective of our study was to evaluate the feasibility and usefulness of the Bayesian classifier for predicting malignant renal cysts on MDCT.
Ninety-three complicated cysts with pathologic confirmation were enrolled. Patient age and sex and seven morphologic features of the cysts including the maximum diameter, wall features, wall thickness, septa features, measurable enhancement of the wall and septa, presence of calcification, and presence of an enhancing soft-tissue component were used to train the Bayesian classifier. Four radiologists independently reviewed the MDCT images, and the probability of malignancy in each cyst was rated by the radiologists and the Bayesian classifier. The diagnostic performances of the radiologists' visual decisions and the Bayesian classifier were then compared using receiver operating characteristic (ROC) curve analysis. The sensitivity and specificity were also compared between the visual decisions and the Bayesian classifier.
The area under the ROC curve for predicting malignant renal cysts by the Bayesian classifier was greater than the visual decisions of three readers (reader 1, p = 0.02; reader 2, p < 0.01; reader 4, p = 0.02) and was similar to the visual decision of one reader (reader 3, p = 0.51). The specificity for predicting malignant renal cysts was greater by the Bayesian classifier than by the visual decisions in readers 2 (p = 0.04) and 4 (p = 0.02) and was similar in readers 1 (p = 0.68) and 3 (p = 1.00). In terms of sensitivity, there was no significant difference between the Bayesian classifier and the visual decisions in all four readers (p > 0.05).
For predicting malignant renal cysts on MDCT, the Bayesian classifier is feasible and may improve diagnostic performance.
American Journal of Roentgenology 09/2009; 193(2):W106-11. · 2.78 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Previously, we showed that hypoxia induces ligand-independent estrogen receptor (ER)alpha activation. In this study, we found that hypoxia activated the ER beta-mediated transcriptional response in HEK293 cells in the absence of estrogen. ER beta transactivation was induced by the expression of the hypoxia-inducible factor 1 alpha (HIF-1 alpha) under normoxia. ER beta interacted with HIF-1 alpha, and SRC1 and CBP potentiated the effect of HIF-1 alpha on ER beta-mediated transcription. We then examined the effect of ER beta on HIF1-alpha transactivation. Surprisingly, ER beta attenuated the transcriptional activity of HIF-1 alpha, as measured by HRE-driven reporter gene expression and hypoxic induction of VEGF mRNA in HEK293 cells. Taken together, these data show that HIF-1 alpha activates ER beta-mediated transcription in the absence of a ligand, and ER beta inhibits HIF-1 alpha-mediated transcription.
FEBS letters 04/2009; 583(8):1314-8. · 3.54 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: We studied the estrogenic activity and cellular effect of wild yam extract in MCF-7 human breast cancer cells. The extract increased the activity of the progesterone receptor and pS2 genes at the mRNA levels in human breast cancer MCF-7 cells, although the effects were not as prominent as those of 17beta-estradiol (E(2)). Western blot analysis showed that the level of estrogen receptor alpha protein was down-regulated after treatment with E(2) or wild yam extract. Wild yam extract also inhibited proliferation of MCF-7 cells. These data indicate that wild yam extract acts as a weak phytoestrogen and protects against proliferation in human breast carcinoma MCF-7 cells.
The American Journal of Chinese Medicine 02/2009; 37(1):159-67. · 1.98 Impact Factor
-
J. Digital Imaging. 01/2009; 22:136-148.
-
[show abstract]
[hide abstract]
ABSTRACT: Machine classifiers have been used to automate quantitative analysis and avoid intra-inter-reader variability in previous studies. The selection of an appropriate classification scheme is important for improving performance based on the characteristics of the data set. This paper investigated the performance of several machine classifiers for differentiating obstructive lung diseases using texture analysis on various ROI (region of interest) sizes. 265 high-resolution computerized tomography (HRCT) images were taken from 92 subjects. On each image, two experienced radiologists selected ROIs with various sizes representing area of severe centrilobular emphysema (PLE, n=63), mild centrilobular emphysema (CLE, n=65), bronchiolitis obliterans (BO, n=70) or normal lung (NL, n=67). Four machine classifiers were implemented: naïve Bayesian classifier, Bayesian classifier, ANN (artificial neural net) and SVM (support vector machine). For a testing method, 5-fold cross-validation methods were used and each validation was repeated 20 times. The SVM had the best performance in overall accuracy (in ROI size of 32x32 and 64x64) (t-test, p<0.05). There was no significant overall accuracy difference between Bayesian and ANN (t-test, p<0.05). The naïve Bayesian method performed significantly worse than the other classifiers (t-test, p<0.05). SVM showed the best performance for classification of the obstructive lung diseases in this study.
Computer methods and programs in biomedicine 12/2008; 93(2):206-15. · 1.14 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The motivation is to introduce new shape features and optimize the classifier to improve performance of differentiating obstructive lung diseases, based on high-resolution computerized tomography (HRCT) images. Two hundred sixty-five HRCT images from 82 subjects were selected. On each image, two experienced radiologists selected regions of interest (ROIs) representing area of severe centrilobular emphysema, mild centrilobular emphysema, bronchiolitis obliterans, or normal lung. Besides 13 textural features, additional 11 shape features were employed to evaluate the contribution of shape features. To optimize the system, various ROI size (16 x 16, 32 x 32, and 64 x 64 pixels) and other classifier parameters were tested. For automated classification, the Bayesian classifier and support vector machine (SVM) were implemented. To assess cross-validation of the system, a five-folding method was used. In the comparison of methods employing only the textural features, adding shape features yielded the significant improvement of overall sensitivity (7.3%, 6.1%, and 4.1% in the Bayesian and 9.1%, 7.5%, and 6.4% in the SVM, in the ROI size 16 x 16, 32 x 32, 64 x 64 pixels, respectively; t test, P < 0.01). After feature selection, most of cluster shape features were survived ,and the feature selected set shows better performance of the overall sensitivity (93.5 +/- 1.0% in the SVM in the ROI size 64 x 64 pixels; t test, P < 0.01). Adding shape features to conventional texture features is much useful to improve classification performance of obstructive lung diseases in both Bayesian and SVM classifiers. In addition, the shape features contribute more to overall sensitivity in smaller ROI.
Journal of Digital Imaging 08/2008; 22(2):136-48. · 1.25 Impact Factor
