• Radiation Oncology Journal
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• 제6권1호
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• pp.35-39
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• 1988

From Jan.1984 to Dec. 1986, 90 patients with lung cancer were treated at the Department of Radiation Therapy in Hanyang University Hospital. Histopathologically, 67 cases of them were the squamous cell carcinoma,7 cases were the adenocarcinoma, 4 cases were the large cell undiffe rentiated carcinoma and 12 cases were the small cell carcinoma. Among the 78 patients with non small cell carcinoma, 50 patients had received radiation dosage above 4000 cGy.40 patient had follow up from 17 months to 53 months. The complete response rate was $7.3\%$ and partial response rate was $68.3\%$. Overall survival at 1, 2 and 3 years were $47.5\%,\;23.5\%\;and\;6.3\%$ respectively. None was survived longer than 38 months. Median survival was 12.2 month for 40 patient and 9 month for stage III, M1 group and 9.5 month for stage III, MO group. In M1 patient no survival was seen after 2 years while in M0 patient $23.3\%$ survival was seen.

• International Journal of Stem Cells
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• 제10권1호
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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.

• Asian Pacific Journal of Cancer Prevention
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• 제14권11호
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• pp.6419-6425
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• 2013

Background: Neoadjuvant chemotherapy (NACT) is a treatment modality whereby chemotherapy is used as the initial treatment of HNSCC in patients presenting with advanced cancer that cannot be treated by other means. It leads to shrinkage of tumours to an operable size without significant compromise to essential oro-facial organs of the patients. The molecular mechanisms behind shrinkage due to NACT is not well elucidated. Materials and Methods: Eleven pairs of primary HNSCCs and adjacent normal epithelium, before and after chemotherapy were screened for cell proliferation and apoptosis. This was followed by immunohistochemical analysis of some cell cycle (LIMD1, RBSP3, CDC25A, CCND1, cMYC, RB, pRB), DNA repair (MLH1, p53) and apoptosis (BAX, BCL2) associated proteins in the same set of samples. Results: Significant decrease in proliferation index and increase in apoptotic index was observed in post-therapy tumors compared to pre-therapy. Increase in the RB/pRB ratio, along with higher expression of RBSP3 and LIMD1 and lower expression of cMYC were observed in post-therapy tumours, while CCND1 and CDC25A remained unchanged. While MLH1 remained unchanged, p53 showed higher expression in post-therapy tumors, indicating inhibition of cell proliferation and induction of apoptosis. Increase in the BAX/BCL2 ratio was observed in post-therapy tumours, indicating up-regulation of apoptosis in response to therapy. Conclusions: Thus, modulation of the G1/S cell cycle regulatory proteins and apoptosis associated proteins might play an important role in tumour shrinkage due to NACT.

• Tuberculosis and Respiratory Diseases
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• 제76권1호
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• pp.1-7
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• 2014

Maintenance therapy has emerged as a novel therapeutic paradigm for advanced non-small-cell lung cancer (NSCLC). Maintenance therapy that aims to sustain a clinically favorable state after first-line chemotherapy has two strategies. Switch maintenance therapy entails switching to a new and non-cross-resistant agent in an alternating or sequential manner, on completion of first-line chemotherapy. Continuous maintenance therapy keeps ongoing administration of a component of the current regimen after four to six cycles of chemotherapy, if there is a stable disease, or better response. Both maintenance therapies can be continued, until disease progression. The potential evidence regarding maintenance therapy includes providing the opportunity to receive additional treatment, through sustaining tumor shrinkage, and delayed emergence of tumor-related symptom. Thus far, debates over the parameters used to predict the effectiveness of maintenance therapy, financial burden, and uncertainty of improving the quality of life exist. Despite many debates, maintenance therapy, which is currently recommended, has been disclosed to be beneficial.

• Biotechnology and Bioprocess Engineering:BBE
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• 제7권5호
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• pp.303-310
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• 2002

Cell therapy applied to wound healing or tissue regeneration presents a revolutionary realm to which principles of gene engineering and delivery may be applied. One promising application is the transplantation of cells into the wounded tissue to help the tissue repair. However, when cells are transplanted from in vitro to in vivo, immune rejection occurs due to the immune response triggered by the activation of T-cell, and the transplanted cells are destroyed by the attack of activated T-cell and lose their function. Immune suppressant such as FK506 is commonly used to suppress immune rejection during transplantation. However, such kind of immune suppressants not only suppresses immune rejection in the periphery of transplanted cells but also suppresses whole immune response system against pathogenic infection. In order to solve this problem, we developed a method to protect the desired cells from immune rejection without impairing whole immune system during cell transplantation. Previously, we reported the success of constructing glomerular epithelial cells for removal of immune complex, in which complement receptor of type 1 (CR1) was over-expressed on the membrane of renal glomerular epithelial cells and could bind immune complex of DNA/anti-DNA-antibody to remove immune complex through phagocy-tosis [1]. Attempting to apply the CR1-expressing cells to cell therapy and evade immune rejection during cell transplantation, we constructed three plasmids containing genes encoding a soluble fusion protein of cytolytic T lymphocyte associated antigen-4 (CTLA4Ig) and an enhanced green fluorescent protein (EGFP). The plasmids were transfected to the above-mentioned glomerular epithelial cells to express both genes simultaneously. Using the clone cells for cell transplantation showed that mice with autoimmune disease prolonged their life significantly as compared with the control mice, and two injections of the cells at the beginning of two weeks resulted in remarkable survivability, whereas it requires half a year and 50 administrations of proteins purified from the same amount of cells to achieve the same effect.

• Archives of Pharmacal Research
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• 제29권11호
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• pp.1032-1041
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• 2006

Extracellular adenosine 5'-triphosphate (ATP) affects the function of many tissues and cells. To confirm the biological activity of ATP on human myeloid leukemic cells, F-36P and HL-60, cells were treated with a variety of concentrations of ATP. The stimulation with extracellular ATP induced the arrest of cell proliferation and cell death. from the analysis of Annexin-V staining and caspase activity by flow cytometry. The Annexin-V positive cells in both cell lines were dramatically increased following ATP stimulation. The expression of P2 purinergic receptor genes was confirmed, such as P2X1, P2X4, P2X5, P2X7 and P2Y1, P2Y2, P2Y4, P2Y5, P2Y6, P2Y11 in both leukemic cell lines. Interestingly, ATP induced intracellular calcium flux in HL-60 cells but not in F-36P cells, as determined by Fluo-3 AM staining. Cell cycle analysis revealed that ATP treatment arrested both F-36P and HL-60 cells at G1/G0. Taken together, these data showed that extracellular ATP via P2 receptor genes was involved in the cell proliferation and survival in human myeloid leukemic cells, HL-60 and F-36P cells by the induction of apoptosis and control of cell cycle. Our data suggest that treatment with extracellular nucleotides may be a novel and powerful therapeutic avenue for myeloid leukemic disease.

• 한국동물생명공학회지
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• 제37권2호
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• pp.67-79
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• 2022

Currently, there is no treatment to reverse or cure heart failure caused by ischemic heart disease and myocardial infarction despite the remarkable advances in modern medicine. In addition, there is a lack of evidence regarding the existence of stem cells involved in the proliferation and regeneration of cardiomyocytes in adult hearts. As an alternative solution to overcome this problem, protocols for differentiating human pluripotent stem cell (hPSC) into cardiomyocyte have been established, which further led to the development of cell therapy in major leading countries in this field. Recently, clinical studies have confirmed the safety of hPSC-derived cardiac progenitor cells (CPCs). Although several institutions have shown progress in their research on cell therapy using hPSC-derived cardiomyocytes, the functions of cardiomyocytes used for transplantation remain to be those of immature cardiomyocytes, which poses a risk of graft-induced arrhythmias in the early stage of transplantation. Over the last decade, research aimed at achieving maturation of immature cardiomyocytes, showing same characteristics as those of mature cardiomyocytes, has been actively conducted using various approaches at leading research institutes worldwide. However, challenges remain in technological development for effective generation of mature cardiomyocytes with the same properties as those present in the adult hearts. Therefore, in this review, we provide an overview of the technological development status for maturation methods of hPSC-derived cardiomyocytes and present a direction for future development of maturation techniques.

• BMB Reports
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• 제48권4호
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• pp.193-199
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• 2015

Degenerative retinal diseases affect millions of people worldwide, which can lead to the loss of vision. However, therapeutic approaches that can reverse this process are limited. Recent efforts have allowed the possibility of the stem cell-based regeneration of retinal cells and repair of injured retinal tissues. Although the direct differentiation of pluripotent stem cells into terminally differentiated photoreceptor cells comprises one approach, a series of studies revealed the intrinsic regenerative potential of the retina using endogenous retinal stem cells. Muller glial cells, ciliary pigment epithelial cells, and retinal pigment epithelial cells are candidates for such retinal stem cells that can differentiate into multiple types of retinal cells and be integrated into injured or developing retina. In this review, we explore our current understanding of the cellular identity of these candidate retinal stem cells and their therapeutic potential for cell therapy against degenerative retinal diseases. [BMB Reports 2015; 48(4): 193-199]

• BMB Reports
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• 제55권2호
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• pp.65-71
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• 2022

Regenerative medicine is a research field that develops methods to restore damaged cell or tissue function by regeneration, repair or replacement. Stem cells are the raw material of the body that is ultimately used from the point of view of regenerative medicine, and stem cell therapy uses cells themselves or their derivatives to promote responses to diseases and dysfunctions, the ultimate goal of regenerative medicine. Stem cell-derived extracellular vesicles (EVs) are recognized as an attractive source because they can enrich exogenous microRNAs (miRNAs) by targeting pathological recipient cells for disease therapy and can overcome the obstacles faced by current cell therapy agents. However, there are some limitations that need to be addressed before using miRNA-enriched EVs derived from stem cells for multiplexed therapeutic targeting in many diseases. Here, we review various roles on miRNA-based stem cell EVs that can induce effective and stable functional improvement of stem cell-derived EVs. In addition, we introduce and review the implications of several miRNA-enriched EV therapies improved by multiplexed targeting in diseases involving the circulatory system and nervous system. This systemic review may offer potential roles for stem cell-derived therapeutics with multiplexed targeting.

• Radiation Oncology Journal
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• 제11권2호
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• pp.285-294
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• 1993

A total of forty patients with resected N2 stage non-small cell lung cancer treated with postoperative adjuvant radiation therapy between Jan. 1975 and Dec. 1990 at the Department of Radiation Oncology, Yonsei University College of Medicine, Yonsei Cancer Center were retrospectively analysed to evaluate whether postoperative radiation therapy improves survival. Patterns of failure and prognostic factors affecting survival were also analysed. The 5 year overall and disease free survival rate were $26.3\%,\;27.3\%$ and median survival 23.5 months. The 5 year survival rates by T-stage were $T1\;66.7\%,\;T2\;25.6\%\;and\;T3\;12.5\%.$ Loco-regional failure rate was $14.3\%$ and distant metastasis rate was $42.9\%$ and both $2.9\%.$ Statistically significant factor affecting distant failure rate was number of postitive lymph nodes(>=4). This retrospective study suggests that postoperative radiation therapy in resected N2 stage non-small cell lung cancer can reduce loco-regional recurrence and may improve survival rate as compared with other studies which were treated by surgery alone. Further study of systemic control is also needed due to high rate of distant metastasis.