• Title/Summary/Keyword: Normal tissue

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Reverting Gene Expression Pattern of Cancer into Normal-Like Using Cycle-Consistent Adversarial Network

  • Lee, Chan-hee;Ahn, TaeJin
    • International Journal of Advanced Culture Technology
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    • v.6 no.4
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    • pp.275-283
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    • 2018
  • Cancer show distinct pattern of gene expression when it is compared to normal. This difference results malignant characteristic of cancer. Many cancer drugs are targeting this difference so that it can selectively kill cancer cells. One of the recent demand for personalized treating cancer is retrieving normal tissue from a patient so that the gene expression difference between cancer and normal be assessed. However, in most clinical situation it is hard to retrieve normal tissue from a patient. This is because biopsy of normal tissues may cause damage to the organ function or a risk of infection or side effect what a patient to take. Thus, there is a challenge to estimate normal cell's gene expression where cancers are originated from without taking additional biopsy. In this paper, we propose in-silico based prediction of normal cell's gene expression from gene expression data of a tumor sample. We call this challenge as reverting the cancer into normal. We divided this challenge into two parts. The first part is making a generator that is able to fool a pretrained discriminator. Pretrained discriminator is from the training of public data (9,601 cancers, 7,240 normals) which shows 0.997 of accuracy to discriminate if a given gene expression pattern is cancer or normal. Deceiving this pretrained discriminator means our method is capable of generating very normal-like gene expression data. The second part of the challenge is to address whether generated normal is similar to true reverse form of the input cancer data. We used, cycle-consistent adversarial networks to approach our challenges, since this network is capable of translating one domain to the other while maintaining original domain's feature and at the same time adding the new domain's feature. We evaluated that, if we put cancer data into a cycle-consistent adversarial network, it could retain most of the information from the input (cancer) and at the same time change the data into normal. We also evaluated if this generated gene expression of normal tissue would be the biological reverse form of the gene expression of cancer used as an input.

A STUDY OF RELATIVE PROPORTIONS OF SKELETAL AND SOFT TISSUES OF CHIN IN NORMAL KOREAN ADULTS (한국 정상성인에서 이부의 골격 및 연조직의 상대적 비율에 관한 연구)

  • Lee, Jae-Hwy;Kim, Soo-Hyiun;Hwang, Byung-Nam;Lee, Jeong-Keun
    • Maxillofacial Plastic and Reconstructive Surgery
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    • v.18 no.2
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    • pp.208-216
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    • 1996
  • The esthetics of chin contour is very important in facial deformities, and the quantity of soft tissue overlying the symphysis can be helpful to the correct diagnosis and surgical treatment for optimal facial harmony. The objectives of this study is to measure the different thicknesses of skeletal and soft tissues of chin on lateral cephalometric radiographs, to obtain the mean values of normal Korean adults, and to investigate the relative proportions of skeletal and soft tissues of chin. The results were as follows ; 1. In normal Korean adults, the relative proportions of the distances of soft tissue toward skeletal tissue were 1.5 in B point and 0.95 in Pg, and there were significant difference between male and female in the relative proportion of Pg (p<0.05). The relative proportion of the distances of vertical soft tissue toward horizontal soft tissue of Me was 1.91, and there were not significant difference between male and female. 2. In normal Korean adults, the distances of skeletal and soft tissues of chin showed no correlation, but the distances of vertical and horizontal soft tissues of Me showed high correlation (p<0.01). 3. In normal Korean adults, the correlations among the distances of each skeletal and soft tissues of chin were significantly high in both of male and female (p<0.01). Among the relative proportions of the distances of skeletal and soft tissues, the correlations of the proportions of B point and Mp and the proportions of Mp and Pg were significantly high (p<0.01).

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Facial soft tissue measuring analysis of normal occlusion using three-dimensional CT imaging (3차원 CT 영상을 이용한 정상교합자의 안면 연조직 계측 분석)

  • Han, Soo-Yeon;Baik, Hyoung-Seon;Kim, Kee-Deog;Yu, Hyung-Seog
    • The korean journal of orthodontics
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    • v.35 no.6 s.113
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    • pp.409-419
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    • 2005
  • Studies for diagnostic analysis using three-dimensional (3D) CT images are recently in progress and needs for 3D craniofacial analysis are increasing in the fields of orthodontics. It is especially essential to analyze the facial soft tissue after orthodontic treatment and orthognathic surgery. In this study 3D CT images of adults with normal occlusion were taken to analyze the facial soft tissue. Norms were obtained from CT images of adults with normal occlusion (12 males, 11 females) using a computer program named V works 4.0 program. 3D coordinate planes were established using soft tissue Nasion as the reference point and a total of 20 reproducible landmarks of facial soft tissue were obtained using the multiple reconstructive sectional images (axial, sagittal and coronal images) of the V works 4.0 program: soft tissue Nasion, Pronasale, Subnasale, Upper lip center, Lower lip center, soft tissue B, soft tissue Pogonion, soft tissue Menton, Endocanthion (Rt/Lt), Alare lateralis (Rt/Lt), Cheilion (Rt/Lt), soft tissue Gonion (Rt/Lt), Tragus (Rt/Lt), and Zygomatic point (Rt/Lt). According to the established landmarks and measuring method, the 3D CT images of adults with normal occlusion were measured and the normal positional measurements and their Net (${\delta}=\sqrt{{X^2}+{Y^2}+{Z^2}}$) values were obtained using V surgery program, In the linear measurement between landmarks, there was a significant difference between males and females except Na' -Sn and En(Rt)-En(Lt). The normal ranges of Na'-Zy, Na'-Ch and Na'-Go' (facial depth) were obtained, which was difficult to measure by two-dimensional (2D) cephalometric analysis and facial photographs. These data may be used as references for 3D diagnosis and treatment planning for patients with malocclusion and dentofacial deformity.

Elevated Aurora Kinase A Protein Expression in Diabetic Skin Tissue

  • Cho, Moon Kyun;An, Je Min;Kim, Chul Han;Kang, Sang Gue
    • Archives of Plastic Surgery
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    • v.41 no.1
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    • pp.35-39
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    • 2014
  • Background Aurora kinase A (Aurora-A) plays an important role in the regulation of mitosis and cytokinesis. Dysregulated Aurora-A leads to mitotic faults and results in pathological conditions. No studies on Aurora-A expression in human diabetic skin tissue have been reported. In light of this, we explored the expression of Aurora-A in human diabetic skin tissue. Methods Aurora-A protein was evaluated by western blotting in 6 human diabetic skin tissue and 6 normal skin specimens. Results Increased expression of Aurora-A protein was detected in all diabetic skin tissue samples in both western blot analysis and immunohistochemical staining. However, in the case of the normal skin tissue, no bands of Aurora-A protein were detected in either the western blotting analysis or the immunohistochemical staining. Conclusions Thus far, there have been no studies on the expression of Aurora-A in diabetic skin tissue. However, we believe that oxidative DNA damage related to the expression of Aurora-A protein and Aurora-A could be involved inhuman diabetic skin tissue.

Feasibility of fully automated classification of whole slide images based on deep learning

  • Cho, Kyung-Ok;Lee, Sung Hak;Jang, Hyun-Jong
    • The Korean Journal of Physiology and Pharmacology
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    • v.24 no.1
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    • pp.89-99
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    • 2020
  • Although microscopic analysis of tissue slides has been the basis for disease diagnosis for decades, intra- and inter-observer variabilities remain issues to be resolved. The recent introduction of digital scanners has allowed for using deep learning in the analysis of tissue images because many whole slide images (WSIs) are accessible to researchers. In the present study, we investigated the possibility of a deep learning-based, fully automated, computer-aided diagnosis system with WSIs from a stomach adenocarcinoma dataset. Three different convolutional neural network architectures were tested to determine the better architecture for tissue classifier. Each network was trained to classify small tissue patches into normal or tumor. Based on the patch-level classification, tumor probability heatmaps can be overlaid on tissue images. We observed three different tissue patterns, including clear normal, clear tumor and ambiguous cases. We suggest that longer inspection time can be assigned to ambiguous cases compared to clear normal cases, increasing the accuracy and efficiency of histopathologic diagnosis by pre-evaluating the status of the WSIs. When the classifier was tested with completely different WSI dataset, the performance was not optimal because of the different tissue preparation quality. By including a small amount of data from the new dataset for training, the performance for the new dataset was much enhanced. These results indicated that WSI dataset should include tissues prepared from many different preparation conditions to construct a generalized tissue classifier. Thus, multi-national/multi-center dataset should be built for the application of deep learning in the real world medical practice.

The Effects of Low Power Laser Treatment on Tissue Inflammatory Reactions in the Linear Incision Wound on Rat Skin (흰 쥐의 선상 절개 창상모델에서 저출력 레이저 자극이 조직 염증반응에 미치는 영향)

  • Lim, In-Hyuk;Lee, Jeong-Weon;Kim, Hyun-Sook
    • Physical Therapy Korea
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    • v.10 no.2
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    • pp.61-70
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    • 2003
  • The purposes of this study was to evaluate the effect of low power GaAsAl laser on tissue contraction in a linear incision wound on rat skin. The linear incision wound was made on the midline of the backside in the experimental animals. Low power laser applications with different intensities such as 3, 6, or 10 mW were applied to the experimental animals twice a day for 10 days. On either the seventh or tenth postoperative day, the quantitative analysis of the inflammatory reaction surrounding the linear incision wounds on the rats were performed using enzymatical analysis of myeloperoxidase (MPO) activity. The number of neutrophil was $.07-1.0{\times}106/m{\ell}$ from a normal blood sample that was obtained from the normal experimental animals. Each concentration of neutrophil showed .04-.62 unit activity of MPO. Therefore, the 6 unit activity of MPO per neutrophil was $.57{\pm}.014{\times}10^{-6}$ unit. On the 7th and 10th post operative day, non treated tissues demonstrated increased MPO activity as compared to that of normal tissue. These data indicated that the inflammatory reaction of tissue was induced after wound induction and the MPO activity were increased in the inflammed tissues. While both 3 mW or 6 mW intensity of laser treatments did not affect the tissue MPO activity, 10 mW intensity of laser treatment significantly decreased the tissue MPO activity on the 7th and 10th post operative day. These data demonstrated that only 10 mW intensity of laser treatment successfully suppressed tissue inflammatory reaction after wound induction. In conclusion, these findings suggested that 10 mW of GaAIAs laser treatments effectively suppressed the inflammatory reaction of tissue that was induced during the wound healing process.

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Proteomic Analysis of Colonic Mucosal Tissue from Tuberculous and Ulcerative Colitis Patients

  • Kwon, Seong-Chun;Won, Kyung-Jong;Jung, Seoung-Hyo;Lee, Kang-Pa;Lee, Dong-Youb;Park, Eun-Seok;Kim, Bok-Yung;Cheon, Gab-Jin;Han, Koon-Hee
    • The Korean Journal of Physiology and Pharmacology
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    • v.16 no.3
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    • pp.193-198
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    • 2012
  • Changes in the expression profiles of specific proteins leads to serious human diseases, including colitis. The proteomic changes related to colitis and the differential expression between tuberculous (TC) and ulcerative colitis (UC) in colon tissue from colitis patients has not been defined. We therefore performed a proteomic analysis of human TC and UC mucosal tissue. Total protein was obtained from the colon mucosal tissue of normal, TC, and UC patients, and resolved by 2-dimensional electrophoresis (2-DE). The results were analyzed with PDQuest using silver staining. We used matrix-assisted laser desorption ionization time-of-flight/time-of-flight spectrometry (MALDI TOF/TOF) to identify proteins differentially expressed in TC and UC. Of the over 1,000 proteins isolated, three in TC tissue and two in UC tissue displayed altered expression when compared to normal tissue. Moreover, two proteins were differentially expressed in a comparative analysis between TC and UC. These were identified as mutant ${\beta}$-actin, ${\alpha}$-enolase and Charcot-Leyden crystal protein. In particular, the expression of ${\alpha}$-enolase was significantly greater in TC compared with normal tissue, but decreased in comparison to UC, implying that ${\alpha}$-enolase may represent a biomarker for differential diagnosis of TC and UC. This study therefore provides a valuable resource for the molecular and diagnostic analysis of human colitis.

Expression of ER, PR, C-erbB-2 and Ki-67 in Endometrial Carcinoma and their Relationships with the Clinicopathological Features

  • Yu, Cui-Ge;Jiang, Xiang-Yang;Li, Bin;Gan, Lu;Huang, Jian-Feng
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.15
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    • pp.6789-6794
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    • 2015
  • Background: To analyze the expression of estrogen receptors (ER), progesterone receptors (PR), C-erbB-2 and Ki-67 in endometrial carcinoma (EC) and their relationships with the clinicopathological features. Materials and Methods: Sixty-seven EC samples, 53 normal endometrial samples and 53 atypical hyperplasia endometrial samples were all selected in Shaanxi Provincial People's Hospital from Jun., 2012 to Jun., 2014. The expression of ER, PR, C-erbB-2 and Ki-67 in EC tissue, normal endometrial tissue and atypical hyperplasia endometrial tissue was respectively detected using immunohistochemical SP method. The relationships between the expression of ER, PR, C-erbB-2 and Ki-67 and the patients' clinicopathological features as well as their correlations in EC tissue were also analyzed. Results: The positive expression rates of ER and PR in EC tissue were 44.8% and 41.8%, respectively, dramatically lower than in atypical hyperplasia endometrial tissue and normal endometrial tissue (P<0.01). The positive expression rates of C-erbB-2 and Ki-67 in EC tissue were 80.6% and 64.2%, respectively, significantly higher than in atypical hyperplasia endometrial tissue and normal endometrial tissue (P<0.01). In EC tissue, the expression of ER and PR was closely associated with the differentiated degrees and depth of myometrial invasion (P<0.05), while that of C-erbB-2 and Ki-67 with the clinical staging, differentiated degrees, depth of myometrial invasion and presence or absence of lymph node metastasis (P<0.05). Spearman correlation analysis further displayed that the expression of ER was positively correlated with PR (r=0.393, P=0.001), but negatively with C-erbB-2 and Ki-67 (r=-0.469, P=0.000; r=-0.329, P=0.007); The expression of PR was negatively correlated with C-erbB-2 and Ki-67 (r=-0.273, P=0.025; r=-0.251, P=0.041), but that of C-erbB-2 positively with Ki-67 (r=0.342, P=0.005). Conclusions: Abnormal expression of ER, PR, C-erbB2 and Ki-67 might play an important role in endometrial malignant transformation and cell differentiation, so their joint detection is likely to be a comprehensive combination of immune factors, which is of great importance for EC prognosis.

Cryptotanshinone promotes brown fat activity by AMPK activation to inhibit obesity

  • Jie Ni;Aili Ye;Liya Gong;Xiafei Zhao;Sisi Fu;Jieya Guo
    • Nutrition Research and Practice
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    • v.18 no.4
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    • pp.479-497
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    • 2024
  • BACKGROUND/OBJECTIVES: Activating brown adipose tissue (BAT) and browning of white adipose tissue (WAT) can protect against obesity and obesity-related metabolic conditions. Cryptotanshinone (CT) regulates lipid metabolism and significantly ameliorates insulin resistance. Adenosine-5'-monophosphate (AMP)-activated protein kinase (AMPK), a receptor for cellular energy metabolism, is believed to regulate brown fat activity in humans. MATERIALS/METHODS: The in vivo study included high-fat-fed obese mice administered orally 200/400 mg/kg/d CT. They were evaluated through weight measurement, the intraperitoneal glucose tolerance test (IPGTT), intraperitoneal insulin tolerance test (IPITT), cold stimulation test, serum lipid (total cholesterol, triglycerides, and low-density lipoprotein) measurement, hematoxylin and eosin staining, and immunohistochemistry. Furthermore, the in vitro study investigated primary adipose mesenchymal stem cells (MSCs) with incubation of CT and AMPK agonists (acadesine)/inhibitor (Compound C). Cells were evaluated using Oil Red O staining, Alizarin red staining, flow cytometry, and immunofluorescence staining to identify and observe the osteogenic versus adipogenic differentiation. Quantitative real-time polymerase chain reaction and the Western blot were used to observe related gene expression. RESULTS: In the diet-induced obesity mouse model mice CT suppressed body weight, food intake, glucose levels in the IPGTT and IPTT, serum lipids, the volume of adipose tissue, and increased thermogenesis, uncoupling protein 1, and the AMPK pathway expression. In the in vitro study, CT prevented the formation of lipid droplets from MSCs while activating brown genes and the AMPK pathway. AMPK activator enhanced CT's effects, while the AMPK inhibitor reversed the effects of CT. CONCLUSION: CT promotes adipose tissue browning to increase body thermogenesis and reduce obesity by activating the AMPK pathway. This study provides an experimental foundation for the use of CT in obesity treatment.