Identification of the Thioredoxin-Like 2 Autoantibody as a Specific Biomarker for Triple-Negative Breast Cancer / 한국유방암학회지

Triple-negative breast cancer (TNBC) has a higher risk of death within 5 years of being diagnosed than the other forms of breast cancer. It is the second leading cause of death due to cancer among women. Currently, however, no diagnostic blood-based biomarker exists to identify the early stages of TNBC. To address this point, we utilized a human protein microarray system to identify serum autoantibodies that showed different expression patterns between TNBC and normal serum samples, and identified five autoantibodies showing TNBC-specific expression. Among them, we selected the thioredoxin-like 2 (TXNL2) autoantibody and evaluated its diagnostic relevance by dot blot analysis with the recombinant TXNL2 protein. We demonstrated that the TXNL2 autoantibody showed 2- to 6-fold higher expression in TNBC samples than in normal samples suggesting that serum TXNL2 autoantibodies are potential biomarkers for TNBC.

Interactome Analysis Reveals that Heterochromatin Protein 1gamma (HP1gamma) Is Associated with the DNA Damage Response Pathway / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Heterochromatin protein 1gamma (HP1gamma) interacts with chromosomes by binding to lysine 9-methylated histone H3 or DNA/RNA. HP1gamma is involved in various biological processes. The purpose of this study is to gain an understanding of how HP1gamma functions in these processes by identifying HP1gamma-binding proteins using mass spectrometry. MATERIALS AND METHODS: We performed affinity purification of HP1gamma-binding proteins using G1/S phase or prometaphase HEK293T cell lysates that transiently express mock or FLAG-HP1gamma. Coomassie staining was performed for HP1gamma-binding complexes, using cell lysates prepared by affinity chromatography FLAG-agarose beads, and the bands were digested and then analyzed using a mass spectrometry. RESULTS: We identified 99 HP1gamma-binding proteins with diverse cellular functions, including spliceosome, regulation of the actin cytoskeleton, tight junction, pathogenic Escherichia coli infection, mammalian target of rapamycin signaling pathway, nucleotide excision repair, DNA replication, homologous recombination, and mismatch repair. CONCLUSION: Our results suggested that HP1gamma is functionally active in DNA damage response via protein-protein interaction.

Automatic Four-Chamber Segmentation Using Level-Set Method and Split Energy Function / 대한의료정보학회지

OBJECTIVES: In this paper, we present an automatic method to segment four chambers by extracting a whole heart, separating the left and right sides of the heart, and spliting the atrium and ventricle regions from each heart in cardiac computed tomography angiography (CTA) efficiently. METHODS: We smooth the images by applying filters to remove noise. Next, the volume of interest is detected by using k-means clustering. In this step, the whole heart is coarsely extracted, and it is used for seed volumes in the next step. Then, we detect seed volumes using a geometric analysis based on anatomical information and separate the left and right heart regions with the power watershed algorithm. Finally, we refine the left and right sides of the heart using the level-set method, and extract the atrium and ventricle from the left and right heart regions using the split energy function. RESULTS: We tested the proposed heart segmentation method using 20 clinical scan datasets which were acquired from various patients. To validate the proposed heart segmentation method, we evaluated its accuracy in segmenting four chambers based on four error evaluation metrics. The average values of differences between the manual and automatic segmentations were less than 3.3%, approximately. CONCLUSIONS: The proposed method extracts the four chambers of the heart accurately, demonstrating that this approach can assist the cardiologist.

Comparative Effects of Ibandronate and Paclitaxel on Immunocompetent Bone Metastasis Model

PURPOSE: Bone metastasis invariably increases morbidity and mortality. This study compares the effects of ibandronate and paclitaxel on bone structure and its mechanical properties and biochemical turnover in resorption markers using an immunocompetent Walker 256-Sprague-Dawley model, which was subjected to tumor-induced osteolysis. MATERIALS AND METHODS: Seventy rats were divided equally into 4 groups: 1) sham group (SHAM), 2) tumor group (CANC), 3) ibandronate treated group (IBAN), and 4) paclitaxel treated group (PAC). Morphological indices [bone volume fraction (BV/TV), trabecular number (Tb.N), trabecular thickness (Tb.Th), trabecular separation (Tb.Sp)] and mechanical properties (failure load, stiffness) were evaluated after thirty days of treatment period. Bone resorption rate was analysed using serum deoxypyridinoline (Dpd) concentrations. RESULTS: Morphological indices showed that ibandronate (anti-resorptive drug) had a better effect in treating tumor-induced architectural changes in bone than paclitaxel (chemotherapeutic drug). The deterioration in bone architecture was reflected in the biomechanical properties of bone as studied with decreased failure load (F(x)) and stiffness (S) of the bone on the 30th day postsurgery. Dpd concentrations were significantly lower in the IBAN group, indicating successful inhibition of bone resorption and destruction. CONCLUSION: Ibandronate was found to be as effective as higher doses of paclitaxel in maintaining stiffness of bone. Paclitaxel treatment did not appear to inhibit osteoclast resorption, which is contrary to earlier in-vitro literature. Emphasis should be placed on the use of immunocompetent models for examining drug efficacy since it adequately reflects bone metastasis in clinical scenarios.

Intratumoral Heterogeneity of Breast Cancer Xenograft Models: Texture Analysis of Diffusion-Weighted MR Imaging

OBJECTIVE: To investigate whether there is a relationship between texture analysis parameters of apparent diffusion coefficient (ADC) maps and histopathologic features of MCF-7 and MDA-MB-231 xenograft models. MATERIALS AND METHODS: MCF-7 estradiol (+), MCF-7 estradiol (-), and MDA-MB-231 xenograft models were made with approval of the animal care committee. Twelve tumors of MCF-7 estradiol (+), 9 tumors of MCF-7 estradiol (-), and 6 tumors in MDA-MB-231 were included. Diffusion-weighted MR images were obtained on a 9.4-T system. An analysis of the first and second order texture analysis of ADC maps was performed. The texture analysis parameters and histopathologic features were compared among these groups by the analysis of variance test. Correlations between texture parameters and histopathologic features were analyzed. We also evaluated the intraobserver agreement in assessing the texture parameters. RESULTS: MCF-7 estradiol (+) showed a higher standard deviation, maximum, skewness, and kurtosis of ADC values than MCF-7 estradiol (-) and MDA-MB-231 (p < 0.01 for all). The contrast of the MCF-7 groups was higher than that of the MDA-MB-231 (p = 0.004). The correlation (COR) of the texture analysis of MCF-7 groups was lower than that of MDA-MB-231 (p < 0.001). The histopathologic analysis showed that Ki-67mean and Ki-67diff of MCF-7 estradiol (+) were higher than that of MCF-7 estradiol (-) or MDA-MB-231 (p < 0.05). The microvessel density (MVD)mean and MVDdiff of MDA-MB-231 were higher than those of MCF-7 groups (p < 0.001). A diffuse-multifocal necrosis was more frequently found in MDA-MB-231 (p < 0.001). The proportion of necrosis moderately correlated with the contrast (r = -0.438, p = 0.022) and strongly with COR (r = 0.540, p = 0.004). Standard deviation (r = 0.622, r = 0.437), skewness (r = 0.404, r = 0.484), and kurtosis (r = 0.408, r = 0.452) correlated with Ki-67mean and Ki-67diff (p < 0.05 for all). COR moderately correlated with Ki-67diff (r = -0.388, p = 0.045). Skewness (r = -0.643, r = -0.464), kurtosis (r = -0.581, r = -0.389), contrast (r = -0.473, r = -0.549) and COR (r = 0.588, r = 0.580) correlated with MVDmean and MVDdiff (p < 0.05 for all). CONCLUSION: The texture analysis of ADC maps may help to determine the intratumoral spatial heterogeneity of necrosis patterns, amount of cellular proliferation and the vascularity in MCF-7 and MDA-MB-231 xenograft breast cancer models.

A Study of Joint Space Narrowing and Erosion in Rheumatoid Arthritis / 대한의료정보학회지

OBJECTIVE: This study was conducted to measure radiographic joint space width and to estimate erosion in the hands of patients with rheumatoid arthritis. It showed that joint space width, homogeneity, and invariant moments are parameters to discriminate between the normal and the rheumatoid joint. METHODS: In order to measure the joint space width and to estimate erosion in the finger joint, 32 radiographic images were used - 16 images for training and 16 images for testing. The joint space width was measured in order to quantify the joint space narrowing. Also, homogeneity and invariant moments was computed in order to quantify erosion. Finally, artificial neural networks were constructed and tested as a classifier distinguishing between the normal and the rheumatoid joint. RESULTS: The joint space width of normal was 1.04+/-0.15 mm and the width of patients with rheumatoid arthritis was 0.94+/-0.15 mm. The Homogeneity of normal was 16568.83+/-2669.83 and invariant moments were 6843.45+/-2937.55. They were statistically difference (p<.05). Using these characteristics, artificial neural networks showed that they discriminate between normal and rheumatoid arthritis (AUC=0.91). CONCLUSION: Measuring joint space width, estimating homogeneity, and invariant moments provide the capability to distinguish between a normal joint and a rheumatoid joint.

A Study on Pupil and Iris Segmentation of the Anterior Segment of the Eye / 대한의료정보학회지

OBJECTIVE: The goal of this study was to develop a novel pupil and iris segmentation algorithm. We evaluated segmentation performance based on a fractal model. Two methods were compared: Daugman's and our new proposed method. METHODS: We received 200 anterior segment images with 3,872x2,592 pixels. Here we present an active contour model that accurately detects pupil boundaries in order to improve the performance of segmentation systems. We propose a method that uses iris segmentation based on a fractal model. We compared the performance of Daugman's method and the proposed new method and statistically analyzed the results. RESULTS: We manually compared segmentation with the Daugman's method and the new proposed method. The findings showed that the proposed segmentation accuracy was about 2.5 percent higher than Daugman's method. There was a significant difference (p<0.05) between the under and over data between the two methods. CONCLUSION: The results of this study show that the new proposed method was more accurate than the conventional method for the measurement of segmentation of the eye by CAD (Computer-aided Diagnosis).