• Asian Pacific Journal of Cancer Prevention
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• v.16 no.10
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• pp.4161-4168
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• 2015

Colorectal cancer (CRC) is a worldwide health problem, being the third most commonly detected cancer in males and the second in females. Rising CRC incidence trends are mainly regarded as a part of the rapid 'Westernization' of life-style and are associated with calorically excessive high-fat/low-fibre diet, consumption of refined products, lack of physical activity, and obesity. Most recent epidemiological and clinical investigations have consistently evidenced a significant relationship between obesity-driven inflammation in particular steps of colorectal cancer development, including initiation, promotion, progression, and metastasis. Inflammation in obesity occurs by several mechanisms. Roles of imbalanced metabolism (MetS), distinct immune cells, cytokines, and other immune mediators have been suggested in the inflammatory processes. Critical mechanisms are accounted to proinflammatory cytokines (e.g. IL-1, IL-6, IL-8) and tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$). These molecules are secreted by macrophages and are considered as major agents in the transition between acute and chronic inflammation and inflammation-related CRC. The second factor promoting the CRC development in obese individuals is altered adipokine concentrations (leptin and adiponectin). The role of leptin and adiponectin in cancer cell proliferation, invasion, and metastasis is attributable to the activation of several signal transduction pathways (JAK/STAT, mitogen-activated protein kinase (MAPK), phosphatidylinositol 3 kinase (PI3K), mTOR, and 5'AMPK signaling pathways) and multiple dysregulation (COX-2 downregulation, mRNA expression).

• Biomolecules & Therapeutics
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• v.30 no.6
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• pp.553-561
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• 2022

Chronic myeloid leukemia (CML) is a slowly progressing hematopoietic cell disorder. Sphingosine kinase 1 (SPHK1) plays established roles in tumor initiation, progression, and chemotherapy resistance in a wide range of cancers, including leukemia. However, small-molecule inhibitors targeting SPHK1 in CML still need to be developed. This study revealed the role of SPHK1 in CML and investigated the potential anti-leukemic activity of hirsuteine (HST), an indole alkaloid obtained from the oriental plant Uncaria rhynchophylla, in CML cells. These results suggest that SPHK1 is highly expressed in CML cells and that overexpression of SPHK1 represents poor clinical outcomes in CML patients. HST exposure led to G2/M phase arrest, cellular apoptosis, and downregulation of Cyclin B1 and CDC2 and cleavage of Caspase 3 and PARP in CML cells. HST shifted sphingolipid rheostat from sphingosine 1-phosphate (S1P) towards the ceramide coupled with a marked inhibition of SPHK1. Mechanistically, HST significantly blocked SPHK1/S1P/S1PR1 and BCR-ABL/PI3K/Akt pathways. In addition, HST can be docked with residues of SPHK1 and shifts the SPHK1 melting curve, indicating the potential protein-ligand interactions between SPHK1 and HST in both CML cells. SPHK1 overexpression impaired apoptosis and proliferation of CML cells induced by HST alone. These results suggest that HST, which may serve as a novel and specific SPHK1 inhibitor, exerts anti-leukemic activity by inhibiting the SPHK1/S1P/S1PR1 and BCR-ABL/PI3K/Akt pathways in CML cells, thus conferring HST as a promising anti-leukemic drug for CML therapy in the future.

• Journal of Gastric Cancer
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• v.13 no.3
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• pp.129-135
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• 2013

Gastric cancer is the second leading cause of cancer-related deaths worldwide. In advanced and metastatic gastric cancer, the conventional chemotherapy with limited efficacy shows an overall survival period of about 10 months. Patient specific and effective treatments known as personalized cancer therapy is of significant importance. Advances in high-throughput technologies such as microarray and next generation sequencing for genes, protein expression profiles and oncogenic signaling pathways have reinforced the discovery of treatment targets and personalized treatments. However, there are numerous challenges from cancer target discoveries to practical clinical benefits. Although there is a flood of biomarkers and target agents, only a minority of patients are tested and treated accordingly. Numerous molecular target agents have been under investigation for gastric cancer. Currently, targets for gastric cancer include the epidermal growth factor receptor family, mesenchymal-epithelial transition factor axis, and the phosphatidylinositol 3-kinase-AKT-mammalian target of rapamycin pathways. Deeper insights of molecular characteristics for gastric cancer has enabled the molecular classification of gastric cancer, the diagnosis of gastric cancer, the prediction of prognosis, the recognition of gastric cancer driver genes, and the discovery of potential therapeutic targets. Not only have we deeper insights for the molecular diversity of gastric cancer, but we have also prospected both affirmative potentials and hurdles to molecular diagnostics. New paradigm of transdisciplinary team science, which is composed of innovative explorations and clinical investigations of oncologists, geneticists, pathologists, biologists, and bio-informaticians, is mandatory to recognize personalized target therapy.

• Genomics & Informatics
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• v.14 no.2
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• pp.46-52
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• 2016

Diverse somatic mutations have been reported to serve as cancer drivers. Recently, it has also been reported that epigenetic regulation is closely related to cancer development. However, the effect of epigenetic changes on cancer is still elusive. In this study, we analyzed DNA methylation data on colon cancer taken from The Caner Genome Atlas. We found that several promoters were significantly hypermethylated in colon cancer patients. Through clustering analysis of differentially methylated DNA regions, we were able to define subgroups of patients and observed clinical features associated with each subgroup. In addition, we analyzed the functional ontology of aberrantly methylated genes and identified the G-protein-coupled receptor signaling pathway as one of the major pathways affected epigenetically. In conclusion, our analysis shows the possibility of characterizing the clinical features of colon cancer subgroups based on DNA methylation patterns and provides lists of important genes and pathways possibly involved in colon cancer development.

• Translational and Clinical Pharmacology
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• v.26 no.3
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• pp.103-110
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• 2018

The human microbiome is known to play an essential role in influencing host health. Extracellular vesicles (EVs) have also been reported to act on a variety of signaling pathways, distally transport cellular components such as proteins, lipids, and nucleic acid, and have immunomodulatory effects. Here we shall review the current understanding of the intersectionality of the human microbiome and EVs in the emerging field of microbiota-derived EVs and their pharmacological potential. Microbes secrete several classes of EVs: outer membrane vesicles (OMVs), membrane vesicles (MVs), and apoptotic bodies. EV biogenesis is unique to each cell and regulated by sophisticated signaling pathways. EVs are primarily composed of lipids, proteins, nucleic acids, and recent evidence suggests they may also carry metabolites. These components interact with host cells and control various cellular processes by transferring their constituents. The pharmacological potential of microbiome-derived EVs as vaccine candidates, biomarkers, and a smart drug delivery system is a promising area of future research. Therefore, it is necessary to elucidate in detail the mechanisms of microbiome-derived EV action in host health in a multi-disciplinary manner.

• Annals of Clinical Neurophysiology
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• v.1 no.2
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• pp.160-167
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• 1999

Although somatosensory evoked potentials(SSEPs) have been utilized as the useful diagnostic tools in evaluating the wide variety of pathological conditions, such as focal lesions affecting the somatosensory pathways, demyelinating diseases, and detecting the clinically occult abnormality, their neural generators is still considerably uncertain. To appreciate the basis for uncertainties about the origins of SSEPs, consider criteria that must be met to establish a causal relationship between activity in a neural structure and a spine/ scalp-recorded potential. Electrode locations and channel derivations for SSEPs recordings are based on two principles:(1) the waveforms are best recorded from electrode sites on the body surface closest to the presumed generator sources along the somatosensory pathways, and(2) studies of the potential-field distribution of each waveform of interest dictate the best techniques to be used. In this article, authors will describe followings focused on ;(1) the concepts of near field potentials(NFPs) and far field potentials(FFPs) - the voltage of NFPs is highly dependent upon recording electrode position, FFPs are unlike NFPs in that they are widely distributed, their latencies and amplitudes are independent of recording electrode.(2) appropriate montage settings to detect the significant potentials in the median nerve and posterior tibial nerve SSEPs(3) neural generators of various potentials(P9, N13, P14, N18, N20, P37) and their clinical significance in interpretating the results of SSEPs. Especially, Characteristics of N18(longduration, small superimposed inflection) suggested that N18 is a complex wave with multiple generators including brainstem structures and thalamic nuclei. And N18 might be used as the parameter of braindeath. Precise understanding on these facts provide an adequate basis utilizing SSEPs for numerous clinical purposes.

• The Journal of Pediatrics of Korean Medicine
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• v.36 no.1
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• pp.65-77
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• 2022

Objectives The purpose of this study was to understand the public's perception of Korean medical treatment for growth disorders to develop Korean medicine clinical practice guidelines and critical pathways for growth disorders in children and adolescents. Methods A survey was conducted using an online platform targeting 252 adults aged 19 years from May 16, 2021 to May 17, 2021. The questionnaire consisted of questions about the demographic characteristics of respondents; overall perception, experience, and satisfaction with Korean medical treatment for growth disorders; willingness to use or recommend Korean medical treatment for growth disorders; and points for improvement. Results The overall perception of treatment for growth disorders was 3.30 ± 0.892 on a 5-point scale. Concerning the negative reasons, 54.4% of the respondents were concerned about safety; regarding the positive reason, expectations for overall health as well as height growth were the highest at 46.5%. Additionally, there was a high demand for information, such as providing safety information on treatment, presenting evidence for the efficacy of treatment, and standardized clinical process, as points requiring improvement. Conclusions To raise public perception of Korean medical treatment for growth disorders, it is necessary to satisfy the opinions of the public identified through this survey. Therefore, the development and utilization of Korean medicine clinical practice guidelines and critical pathways for growth disorders would play an important role.

• Journal of Korean Medicine Rehabilitation
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• v.33 no.2
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• pp.57-76
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• 2023

Objectives This study aims to develop Korean Medicine Clinical Pathway (CP) based on Clinical Practice Guideline of carpal tunnel syndrome to improve quality of treatment and reduce medical cost to maximize the quality of patient management. Methods A draft version of CP for carpal tunnel syndrome is developed by expert agreement and a prospective case study was carried out based on the draft CP. Twenty experts working at various medical institution answered validity verification survey of developed CP. Fifteen patients enrolled in the prospective case study answered survey on demand and satisfaction. Qualification and adjustment process of the draft CP was conducted based on results of both surveys. Results Final version of CP for carpal tunnel syndrome is confirmed after qualification and adjustment on the draft version. Conclusions CP for carpal tunnel syndrome will provide patients with standardized, high-quality Korean medicine treatment and also reduce financial burden of health insurance by reducing medical cost.

• Annals of Clinical Neurophysiology
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• v.17 no.1
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• pp.1-16
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• 2015

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease that is characterized by progressive death of motor neurons in the cortex, brainstem, and spinal cord. Until now, many treatment strategies have been tested in ALS, but so far only Riluzole has shown efficacy of slightly slowing disease progression. The pathophysiological mechanisms underlying ALS are multifactorial, with a complex interaction between genetic factors and molecular pathways. Other motor neuron disease such as spinal muscular atrophy (SMA) and spinobulbar muscular atrophy (SBMA) are also progressive neurodegenerative disease with loss of motor neuron as ALS. This common thread of motor neuron loss has provided a target for the development of therapies for these motor neuron diseases. A better understanding of these pathogenic mechanisms and the potential pathological relationship between the various cellular processes have suggested novel therapeutic approaches, including stem cell and genetics-based strategies, providing hope for feasible treatment of ALS.

• Annals of Clinical Neurophysiology
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• v.20 no.1
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• pp.12-17
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• 2018

Visual evoked potentials (VEPs) are frequently used to assess the anterior and posterior visual pathways. In particular, the use of VEPs have been increasing in various fields such as evaluation of the optic nerves in patients with multiple sclerosis. The performance of VEP test can be affected by various factors such as stimulus type and subject condition, and its interpretation is also difficult. However, there have been no guidelines for performing and interpreting VEPs in Korea. Therefore, we aimed to provide comprehensive information regarding basic requirement and interpretation for VEPs.