• International Journal of Stem Cells
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• v.10 no.1
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• pp.1-11
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• 2017

Human cardiomyocytes (CMs) cease to proliferate and remain terminally differentiated thereafter, when humans reach the mid-20s. Thus, any damages sustained by myocardium tissue are irreversible, and they require medical interventions to regain functionality. To date, new surgical procedures and drugs have been developed, albeit with limited success, to treat various heart diseases including myocardial infarction. Hence, there is a pressing need to develop more effective treatment methods to address the increasing mortality rate of the heart diseases. Functional CMs are not only an important in vitro cellular tool to model various types of heart diseases for drug development, but they are also a promising therapeutic agent for cell therapy. However, the limited proliferative capacity entails difficulties in acquiring functional CMs in the scale that is required for pathological studies and cell therapy development. Stem cells, human pluripotent stem cells (hPSCs) in particular, have been considered as an unlimited cellular source for providing functional CMs for various applications. Notable progress has already been made: the first clinical trials of hPSCs derived CMs (hPSC-CMs) for treating myocardial infarction was approved in 2015, and their potential use in disease modeling and drug discovery is being fully explored. This concise review gives an account of current development of differentiation, purification and maturation techniques for hPSC-CMs, and their application in cell therapy development and pharmaceutical industries will be discussed with the latest experimental evidence.

• BMB Reports
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• v.56 no.9
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• pp.482-487
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• 2023

Hematopoiesis is regulated by crosstalk between long-term repopulating hematopoietic stem cells (LT-HSCs) and supporting niche cells in the bone marrow (BM). Here, we describe the role of KAI1, which is mainly expressed on LT-HSCs and rarely on other hematopoietic stem-progenitor cells (HSPCs), in niche-mediated LT-HSC maintenance. KAI1 activates TGF-β1/Smad3 signal in LT-HSCs, leading to the induction of CDK inhibitors and inhibition of the cell cycle. The KAI1-binding partner DARC is expressed on macrophages and stabilizes KAI1 on LT-HSCs, promoting their quiescence. Conversely, when DARC+ BM macrophages were absent, the level of surface KAI1 on LT-HSCs decreases, leading to cell-cycle entry, proliferation, and differentiation. Thus, KAI1 acts as a functional surface marker of LT-HSCs that regulates dormancy through interaction with DARC-expressing macrophages in the BM stem cell niche. Recently, we showed very special and rare macrophages expressing α-SMA+ COX2+ & DARC+ induce not only dormancy of LT-HSC through interaction of KAI1-DARC but also protect HSCs by down-regulating ROS through COX2 signaling. In the near future, the strategy to combine KAI1-positive LT-HSCs and α-SMA/Cox2/DARC triple-positive macrophages will improve the efficacy of stem cell transplantation after the ablative chemo-therapy for hematological disorders including leukemia.

• Progress in Medical Physics
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• v.23 no.1
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• pp.8-14
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• 2012

In order to develop a Patient respiratory management system includinga biofeedback function for4-dimentional radiation therapy, this study investigated anoptimal tracking algorithmfor moving target using IR (Infra-red) camera as well as commercial camera. A tracking system was developed by LabVIEW 2010. Motion phantom images were acquired using a camera (IR or commercial). After image process were conducted to convert acquired image to binary image by applying a threshold values, several edge enhance methods such as Sobel, Prewitt, Differentiation, Sigma, Gradient, Roberts, were applied. The targetpattern was defined in the images, and acquired image from a moving targetwas tracked by matching pre-defined tracking pattern. During the matching of imagee, thecoordinateof tracking point was recorded. In order to assess the performance of tracking algorithm, the value of score which represents theaccuracy of pattern matching was defined. To compare the algorithm objectively, we repeat experiments 3 times for 5 minuts for each algorithm. Average valueand standard deviations (SD) of score were automatically calculatedsaved as ASCII format. Score of threshold only was 706, and standard deviation was 84. The value of average and SD for other algorithms which combined edge detection method and thresholdwere 794, 64 in Sobel, 770, 101 in Differentiation, 754, 85 in Gradient, 763, 75 in Prewitt, 777, 93 in Roberts, and 822, 62 in Sigma, respectively. According to score analysis, the most efficient tracking algorithm is the Sigma method. Therefore, 4-dimentional radiation threapy is expected tobemore efficient if threshold and Sigma edge detection method are used together in target tracking.

• Investigative Magnetic Resonance Imaging
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• v.18 no.2
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• pp.120-132
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• 2014

Purpose : To compare dynamic susceptibility contrast imaging, diffusion-weighted imaging, and susceptibility-weighted imaging (SWI) for the differentiation of tumor recurrence and delayed radiation therapy (RT)-related changes in patients treated with RT for primary brain tumors. Materials and Methods: We enrolled 24 patients treated with RT for various primary brain tumors, who showed newly appearing enhancing lesions more than one year after completion of RT on follow-up MRI. The enhancing-lesions were confirmed as recurrences (n=14) or RT-changes (n=10). We calculated the mean values of normalized cerebral blood volume (nCBV), apparent diffusion coefficient (ADC), and proportion of dark signal intensity on SWI (proSWI) for the enhancing-lesions. All the values between the two groups were compared using t-test. A multivariable logistic regression model was used to determine the best predictor of differential diagnosis. The cutoff value of the best predictor obtained from receiver-operating characteristic curve analysis was applied to calculate the sensitivity, specificity, and accuracy for the diagnosis. Results: The mean nCBV value was significantly higher in the recurrence group than in the RT-change group (P=.004), and the mean proSWI was significantly lower in the recurrence group (P<.001). However, no significant difference was observed in the mean ADC values between the two groups. A multivariable logistic regression analysis showed that proSWI was the only independent variable for the differentiation; the sensitivity, specificity, and accuracy were 78.6% (11 of 14), 100% (10 of 10), and 87.5% (21 of 24), respectively. Conclusion: The proSWI was the most promising parameter for the differentiation of newly developed enhancing-lesions more than one year after RT completion in brain tumor patients.

• Bulletin of the Korean Chemical Society
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• v.31 no.7
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• pp.2019-2024
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• 2010

Insulin-like growth factor binding protein 5 (IGFBP-5) plays an important role in controlling cell survival, differentiation and apoptosis. Apoptosis can be induced by an extrinsic pathway involving the ligand-mediated activation of death receptors such as tumor necrosis factor receptor 1 (TNFR1). To determine whether IGFBP-5 and TNFR1 interact as members of the same apoptosis pathway, recombinant IGFBP-5 and TNFR1 were isolated. The expression and purification of the full-length TNFR1 and truncated IGFBP-5 proteins were successfully performed in E. coli. The binding of both IGFBP-5 and TNFR1 proteins was detected by surface plasmon resonance spectroscopy (BIAcore), fluorescence measurement, electron microscopy, and size-exclusion column (SEC) chromatography. IGFBP-5 indeed binds to TNFR1 with an apparent $K_D$ of 9 nM. After measuring the fluorescence emission spectra of purified IGFBP-5 and TNFR1, it was found that the tight interaction of these proteins is accompanied by significant conformational changes of one or both. These results indicate that IGFBP-5 acts potently as a novel ligand for TNFR1.

• Korean Journal of Environmental Biology
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• v.23 no.2 s.58
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• pp.152-156
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• 2005

Ionizing radiation is a well- known therapy factor for human carcinoma cells. Genotoxic stress mediates cell cycle control, transcription and cellular signaling. In this work, we have used a microarray hybridization approach to characterize the cell type-specific transcriptional response of human carcinoma MCF-7 and HeLa cell line to $\gamma-radiation$, such as 4Gy 4hr. We found that exposure to $\gamma-ray$ alters by at least a $log_2$ factor of 1.0 the expression of known genes. Of the 27 genes affected by irradiation, 11 are down- regulated in MCF-7 cells and 2 genes induced by radiation,15 are repressed in HeLa cells. Many genes were involved in known damage- response pathways for cell cycling, transcription factor and cellular signaling response. However, in MCF-7 cells, we observed gene expression pattern in chromatin, apoptosis, stress, differentiation, cytokine, metabolism, ribosome and calcium. In HeLa cells, it showed clearly the expression changes in adhesion and migration, lysosome, brain, genome instability and translation. These insights reveal new therapy directions for studying the human carcinoma cell response to radiation.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.27 no.1
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• pp.65-68
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• 2001

The major manifestations of aplastic anemia are characterized by persistent bone marrow aplasia and peripheral pancytopenia due to defective stem cells in which differentiation is not curtailed or preferential elimination of stem cells with self-renewal capacity, which results in serious complications such as bleeding and infection. Recent advances in the therapeutic modalities, such as bone marrow transplantation and immunosuppressive therapy, and in supportive measures as component transfusion and infection control with better quality of antibiotics resulted in an improved survival and subsequently increased possibility of complications which need surgical intervention. Considering the fact that surgery may not only control complications, but offers the opportunity to give effective therapy for aplastic anemia and therefore improves chances for survival, it is strongly suggested that active surgical intervention should be performed. We report a case of patient with aplastic anemia who had been performed surgical intervention of partial maxillectomy for the squamous cell carcinoma on maxilla without serious complications during perioperative and postoperative period.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.30 no.2
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• pp.136-142
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• 2004

Malignant fibrous histiocytoma(MFH) is the malignant part of mesenchymal cell-originated tumor, which is supposed that the tumor is presented various histologic features consisted of fibrosarcomatic and histiocytic portions. When the tumor is arisen in the head and neck region, the most affected sites are the nasal cavity and paranasal sinuses, and secondly the maxillary alveolar bone is occasionally influenced. Therefore, MFH can readily involve the adjacent alveolar bone. The treatment of MFH in the head and neck is various, that is, the involved sites and the differentiation of tumor must be considered when the tumor is treated. The treatment protocols are subjected to general ones of soft tissue sarcoma, and simple or combination therapy is used in the surgery, chemotherapy and radiation therapy. So, we report a clinical case of chemotherapy involving intraarterial chemotherapy, and surgery of malignant fibrous histiocytoma(MFH) in the maxilla, with review of the literature.

• BMB Reports
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• v.50 no.3
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• pp.117-125
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• 2017

Most of the cancers are still incurable human diseases. According to recent findings, especially targeting cancer stem cells (CSCs) is the most promising therapeutic strategy. CSCs take charge of a cancer hierarchy, harboring stem cell-like properties involving self-renewal and aberrant differentiation potential. Most of all, the presence of CSCs is closely associated with tumorigenesis and therapeutic resistance. Despite the numerous efforts to target CSCs, current anti-cancer therapies are still impeded by CSC-derived cancer malignancies; increased metastases, tumor recurrence, and even acquired resistance against the anti-CSC therapies developed in experimental models. One of the most forceful underlying reasons is a "cancer heterogeneity" due to "CSC plasticity". A comprehensive understanding of CSC-derived heterogeneity will provide novel insights into the establishment of efficient targeting strategies to eliminate CSCs. Here, we introduce findings on mechanisms of CSC reprogramming and CSC plasticity, which give rise to phenotypically varied CSCs. Also, we suggest concepts to improve CSC-targeted therapy in order to overcome therapeutic resistance caused by CSC plasticity and heterogeneity.

• The Journal of Korean Medicine
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• v.19 no.1
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• pp.470-499
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• 1998

For the purpose of designing more successful cancer research, the strategy for cancer study in the field of Traditional Korean Medicine(TKM) during the 21th century was examined from the analysis of trends on cancer study in traditional korean medicine. The results were summarized as follows: 1. So far cancer research in TKM was chiefly done on cytotoxicity, side-effects by chemotherapy, tumor immunology, apoptosis, survival time with S-180 and pulmonary colonization assay and also clonogenic assay, cell adhesion assay, angiogenesis, cell-differentiation and side-effect by radiotherapy were partly performed. 2. It may be ideal that we should study synergistic effect between constituent drugs of prescriptions, tumor immunology, combined therapy between western and oriental medicines by reducing side-effect by radiotherapy and chemotherapy and antimetastasis according to the characteristics of oriental medicine chiefly and also supplement the studies on molecular biology, gene therapy, angiogensis and signal transduction. 3. We had better do specific-field research in cooperation between oriental medical colleges and Korea Institute of Oriental Medicine(KIOM) as well as study a target cancers such as hepatic cancer, pulmonary cancer and gastric cancer more intensively than all cancers domestically. 4. Our country must keep communication with China having many clinical data, Taiwan chiefly doing the combined tharapy between oriental and western medicines, Japan having done basic study actively on cancer.