• Journal of Cancer Prevention
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• v.22 no.4
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• pp.234-240
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• 2017

Background: Lung cancer is the leading cause of cancer-related death worldwide, for which smoking is considered as the primary risk factor. The present study was conducted to determine whether genetic alterations induced by radon exposure are associated with the susceptible risk of lung cancer in never smokers. Methods: To accurately identify mutations within individual tumors, next generation sequencing was conduct for 19 pairs of lung cancer tissue. The associations of germline and somatic variations with radon exposure were visualized using OncoPrint and heatmap graphs. Bioinformatic analysis was performed using various tools. Results: Alterations in several genes were implicated in lung cancer resulting from exposure to radon indoors, namely those in epidermal growth factor receptor (EGFR), tumor protein p53 (TP53), NK2 homeobox 1 (NKX2.1), phosphatase and tensin homolog (PTEN), chromodomain helicase DNA binding protein 7 (CHD7), discoidin domain receptor tyrosine kinase 2 (DDR2), lysine methyltransferase 2C (MLL3), chromodomain helicase DNA binding protein 5 (CHD5), FAT atypical cadherin 1 (FAT1), and dual specificity phosphatase 27 (putative) (DUSP27). Conclusions: While these genes might regulate the carcinogenic pathways of radioactivity, further analysis is needed to determine whether the genes are indeed completely responsible for causing lung cancer in never smokers exposed to residential radon.

• Molecules and Cells
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• v.44 no.10
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• pp.710-722
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• 2021

Hypoxia, or low oxygen tension, is a hallmark of the tumor microenvironment. The hypoxia-inducible factor-1α (HIF-1α) subunit plays a critical role in the adaptive cellular response of hypoxic tumor cells to low oxygen tension by activating gene-expression programs that control cancer cell metabolism, angiogenesis, and therapy resistance. Phosphorylation is involved in the stabilization and regulation of HIF-1α transcriptional activity. HIF-1α is activated by several factors, including the mitogen-activated protein kinase (MAPK) superfamily. MAPK phosphatase 3 (MKP-3) is a cytoplasmic dual-specificity phosphatase specific for extracellular signal-regulated kinase 1/2 (Erk1/2). Recent evidence indicates that hypoxia increases the endogenous levels of both MKP-3 mRNA and protein. However, its role in the response of cells to hypoxia is poorly understood. Herein, we demonstrated that small-interfering RNA (siRNA)-mediated knockdown of MKP-3 enhanced HIF-1α (not HIF-2α) levels. Conversely, MKP-3 overexpression suppressed HIF-1α (not HIF-2α) levels, as well as the expression levels of hypoxia-responsive genes (LDHA, CA9, GLUT-1, and VEGF), in hypoxic colon cancer cells. These findings indicated that MKP-3, induced by HIF-1α in hypoxia, negatively regulates HIF-1α protein levels and hypoxia-responsive genes. However, we also found that long-term hypoxia (>12 h) induced proteasomal degradation of MKP-3 in a lactic acid-dependent manner. Taken together, MKP-3 expression is modulated by the hypoxic conditions prevailing in colon cancer, and plays a role in cellular adaptation to tumor hypoxia and tumor progression. Thus, MKP-3 may serve as a potential therapeutic target for colon cancer treatment.

• Molecules and Cells
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• v.42 no.2
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• pp.183-188
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• 2019

Osteoarthritis (OA) is a naturally occurring, irreversible disorder and a major health burden. The disease is multifactorial, involving both physiological and mechanical processes, but calcium crystals have been associated intimately with its pathogenesis. This study tested the hypothesis that these crystals have a detrimental effect on the differentiation of osteoclasts and bone homeostasis. This study employed an osteoblastosteoclast coculture system that resembles in vivo osteoblastdependent osteoclast differentiation along with $Ca^{2+}$-phosphate-coated culture dishes. The calcium-containing crystals upregulated the expression of RANKL and increased the differentiation of osteoclasts significantly as a result. On the other hand, osteoblast differentiation was unaffected. MicroRNA profiling showed that dual-specificity phosphatases 1 (DUSP1) was associated with the increased RANKL expression. DUSP1 belongs to a family of MAPK phosphatases and is known to inactivate all three groups of MAPKs, p38, JNK, and ERK. Furthermore, knockdown of DUSP1 gene expression suggested that RANKL expression increases significantly in the absence of DUSP1 regulation. Microarray analysis of the DUSP1 mRNA levels in patients with pathological bone diseases also showed that the downregulated DUSP1 expression leads to increased expression of RANKL and consequently to the destruction of the bone observed in these patients. These findings suggest that calcium-containing crystals may play a crucial role in promoting RANKL-induced osteoclastogenesis via DUSP1.

• IMMUNE NETWORK
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• v.23 no.4
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• pp.34.1-34.15
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• 2023

Lung cancer, particularly non-small cell lung cancer (NSCLC) which contributes more than 80% to totally lung cancer cases, remains the leading cause of cancer death and the 5-year survival is less than 20%. Continuous understanding on the mechanisms underlying the pathogenesis of this disease and identification of biomarkers for therapeutic application and response to treatment will help to improve patient survival. Here we found that a molecule known as DUSP10 (also known as MAPK phosphatase 5) is oncogenic in NSCLC. Overexpression of DUSP10 in NSCLC cells resulted in reduced activation of ERK and JNK, but increased activation of p38, which was associated with increased cellular growth and migration. When inoculated in immunodeficient mice, the DUSP10-overexpression NSCLC cells formed larger tumors compared to control cells. The increased growth of DUSP10-overexpression NSCLC cells was associated with increased expression of tumor-promoting cytokines including IL-6 and TGFβ. Importantly, higher DUSP10 expression was associated with poorer prognosis of NSCLC patients. Therefore, DUSP10 could severe as a biomarker for NSCLC prognosis and could be a target for development of therapeutic method for lung cancer treatment.

• Investigative Magnetic Resonance Imaging
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• v.3 no.1
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• pp.66-72
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• 1999

Purpose : To evaluate the usefulness of Dual Echo in Steady State(DESS) image in the diagnosis of chondromalacia of the knee compared with turbo spin-echo MR images Materials and Methods : We included 26 patients with chondromalacia of the knee. MR imaging was obtained with a 1.5T imager. Sagittal and coronal double echo T2 weighted images(TR/TE 3000-4200/16-96msec, FOV $140-160{\times}140-160mm$, matrix size $180{\times}256$, slice thickness 4.0mm, interslice gap 0.5mm), and sagittal DESS image(TR/TE 25.4/9.0msec, flip angle $35-45^{\circ}$, FOV $150-160{\times}150-160mm,{\;}matrix{\;}size{\;}192{\times}256$, effective slice thickness 1.5mm) were obtained. Cartilage lesions were staged according to a modified scheme proposed by Outerbirdge: grade 0, normal; grade 1, softening or/and swelling; grade 2, mild surface fibrillation or/and less than 50% of cartilage thickness; grade 3, severe surface fibrillation or/and loss of more than 50% of cartilage thickness but without exposure of subchondral bone; and grade 4, complete loss of cartilage with subchondral bone exposure. Gradings were determined by two readers with consensus, and patellofemoral, medial and lateral tibiofemoral compartments were evaluated. Results : Arthroscopic findings revealed grade 1 in seven cases, grade 2 in 21 cases, grade 3 in six cases, and grade 4 in 18 cases. Sensitivity of turbo spin-echo MR image was as follows; 0%, 14%, 0%, 61% in each grade, and sensitivity of DESS image was as follows; 0%, 33%, 50%, 67%, in each grade(p=0.001). In the detection of chondromalacic lesions regardless of gradings, sensitivity, specificity and accuracy of conventional MR image were 59.6% 88.6% 78.8%, and of DESS image, 73.1% 88.4%, 82.2%(p=0.007). Conclusion : For chondromalacia of knee joints, DESS images showed higher sensitivity than turbo spin-echo MR images. Therefore, DESS images will be helpful for diagnosis of chondromalacia of knee joints.

• Journal of the Daesoon Academy of Sciences
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• v.35
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• pp.73-107
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• 2020

Daesoon Jinrihoe tends to be perceived as a 'nationalistic religion' by both internal members of the religious body and outside scholars of religious studies. However, the character of this particular nationalistic religion is rather complex. On top of emphasizing the special status of the Korean ethnic group while focusing on nationalism as a nationalistic religion, Daesoon Jinrihoe futrther asserts an implication of the universality of world religion aiming to bring relief to humankind and the world. This dynamic is one of the specificity of nationalistic religion and also the universality of world religion. However, this dual logic of specificity and universality is not characteristic of only Daesoon Jinrihoe. Many religions in the world have also exhibited duplicity as nationalistic religions and world religions. And this thesis pays attention to Sectarian Shinto as it formed in modern Japan. Kyoha Shinto formed when the modern Japanese government established the national Shinto system which had a total of 13 sects. Most of them do not only call themselves a nationalistic religion, inheriting the ethnic tradition of Japanese people, but also jump into overseas missionary work. This started during the Sino-Japanese and Russo-Japanese Wars. With that in mind, how did the overseas missionary work of Sectarian Shinto aspire for status as a world religion while maintaining their identities as nationalistic religions? Furthermore, how did their movements fare in their efforts to become world religions? Thus, this thesis aims to examine the possibility Daesoon Jinrihoe becoming a world religion through some cases of Sectarian Shinto that showed the duplicity as nationalistic religions and world religions. Also, this thesis makes suggestions regarding the future direction of Daesoon Jinrihoe. As such, this paper aims to review the new direction of Daesoon Jinrihoe as it stands on the borderline between being a nationalistic religion and a world religion. This is done by examining the historical flow of theory regarding 'nationalistic religion' or 'minjung religion' which have long been discussed in Korean society. Also examined is the case of Won Buddhism which likewise aims to simultaneosuly be both a nationalistic religion in Korea and a world religion abroad.

• Journal of Yeungnam Medical Science
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• v.25 no.1
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• pp.19-30
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• 2008

Osteoporosis, a disease characterized by low bone mass and microarchitectural deterioration of bone tissue leading to enhanced bone fragility and fracture risk, is a major public health problem. The diagnostic methods for osteoporosis include simple radiography, bone scan, DXA (Dual energy X-ray Absortiometry) and biochemical markers of bone turnover. Optimal treatment and prevention of osteoporosis require modification of risk factors, particularly smoking cessation, adequate physical activity, and attention to diet, in addition to pharmacologic intervention. The estrogens and raloxifene both prevent bone loss in postmenopausal women, and the estrogens probably also decrease the risk of first fracture. There is good evidence that raloxifene prevents further fractures in postmenopausal women who already have had fractures and some evidence that estrogen does as well. Bisphosphonate prevents bone loss and reduces fractures in healthy and osteoporotic postmenopausal women and in osteoporotic men as well. Risedronate is more potent and has fewer side effects than alendronate and reduces the incidence of fractures in osteoporotic women. Calcitonin increases bone mineral density in early postmenopausal women and men with idiopathic osteoporosis, and also reduces the risk of new fractures in osteoporotic women. All of the agents discussed above prevent bone resorption, whereas teriparatide and strontium increase bone formation and are effective in the treatment of osteoporotic women and men. New avenues for targeting osteoporosis will emerge as our knowledge of the regulatory mechanisms of bone remodeling increases, although issues of tissue specificity may remain to be addressed.

• The Korean Journal of Nuclear Medicine
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• v.29 no.4
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• pp.526-532
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• 1995

Introduction : $^{99m}Tc$-(V)-DMSA is a tumor seeking agent that has been used to image medullary carcinoma of thyroid, soft tissue sarcoma and lung cancer. This study was designed to assess the clinical role of $^{99m}Tc$-(V)-DMSA in the diagnosis of head and neck cancers. We has evaluated the diagnostic efficacy of planar and SPECT imaging using $^{99m}Tc$-(V)-DMSA. Patients and Method : Sixty-eight patients with head and neck mass were included in this study. All subjects were diagnosed by biopsy or surgery. Planar and SPECT images were obtained at 2 or 3 hour after intravenous injection of 740 MBq(20 mCi) $^{99m}Tc$-(V)-DMSA. Seventeen patients also underwent SPECT in aging using dual head camera. Result : The diagnostic sensitivity of $^{99m}Tc$-(V)-DMSA planar and SPECT imaging was 65% and 90%, and specificity was 80% and 66%, respectively. The sensitivity of planar imaging in squamous cell carcinoma was similar to overall sensitivity Six metastatic lesion were first diagnosed by scintigraphy. But benign lesions such as Kikuchi syndrome, tuberculous lymphadenitis also revealed increased uptake. Conclusion : $^{99m}Tc$-(V)-DMSA imaging seems to be a promising method in the evaluation of patients with head and neck mass. We recommend SPECT imaging to delineate anatomic localization of the lesion.

• Journal of Life Science
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• v.28 no.10
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• pp.1140-1146
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• 2018

Dual-specificity phosphatases (DUSPs) play a role in cell growth and differentiation by modulating mitogen-activated protein kinases. DUSPs are considered targets for drugs against cancers, diabetes, immune diseases, and neuronal diseases. Part of the DUSP family, DUSP19 modulates c-Jun N-terminal kinase activity and is involved in osteoarthritis pathogenesis. Here, we report screening of cavity-creating mutants and the crystal structure of a cavity-creating L75A mutant of DUSP19 which has significantly enhanced enzyme activity in comparison to the wild-type protein. The crystal structure reveals a well-formed cavity due to the absent Leu75 side chain and a rotation of the active site-bound sulfate ion. Despite the cavity creation, residues surrounding the cavity did not rearrange significantly. Instead, a tightened hydrophobic interaction by a remote tryptophan residue was observed, indicating that the protein folding of the L75A mutant is stabilized by global folding energy minimization, not by local rearrangements in the cavity region. Conformation of the rotated active site sulfate ion resembles that of the phosphor-tyrosine substrate, indicating that cavity creation induces an optimal active site conformation. The activity enhancement by an internal cavity and its structural information provide insight on allosteric modulation of DUSP19 activity and development of therapeutics.

• Korean Journal of Radiology
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• v.24 no.7
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• pp.690-697
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• 2023

Objective: ¹⁸F-FP-CIT positron emission tomography (PET) is known for its high sensitivity and specificity for evaluating striatal dopamine transporter (DAT) binding. Recently, for the early diagnose of Parkinson's disease, many researchers focused on the diagnosis of synucleinopathy in organs involved in non-motor symptoms of Parkinson's disease. We investigated the feasibility of salivary gland uptake on ¹⁸F-FP-CIT PET as a new biomarker in patients with parkinsonism. Materials and Methods: A total of 219 participants with confirmed or presumed parkinsonism, including 54 clinically diagnosed idiopathic Parkinson's disease (IPD), 59 suspected and yet undiagnosed, and 106 with secondary parkinsonism, were enrolled. The standardized uptake value ratio (SUVR) of the salivary glands was measured on both early and delayed ¹⁸F-FP-CIT PET scans using the cerebellum as the reference region. Additionally, the delayed-to-early ratio (DE_ratio) of salivary gland was obtained. The results were compared between patients with different PET patterns. Results: The SUVR in early ¹⁸F-FP-CIT PET scan was significantly higher in patients with IPD pattern compared that in the non-dopaminergic degradation group (0.5 ± 0.19 vs. 0.6 ± 0.21, P < 0.001). Compared with the non-dopaminergic degradation group, the DE_ratio was significantly lower in patients with IPD (5.05 ± 1.7 vs. 4.0 ± 1.31, P < 0.001) or atypical parkinsonism patterns (5.05 ± 1.7 vs. 3.76 ± 0.96, P < 0.05). The DE_ratio was moderately and positively correlated with striatal DAT availability in both the whole striatum (r = 0.37, P < 0.001) and posterior putamen (r = 0.36, P < 0.001). Conclusion: Parkinsonism patients with an IPD pattern exhibited a significant increase in uptake on early ¹⁸F-FP-CIT PET and a decrease in the DE_ratio in the salivary gland. Our findings suggest that salivary gland uptake of dual-phase ¹⁸F-FP-CIT PET can provide diagnostic information on DAT availability in patients with Parkinson's disease.