• Journal of the Korea Society of Computer and Information
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• v.21 no.12
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• pp.139-145
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• 2016

In this paper, we propose to evaluate the effect of Resistin-like molecule alpha (Retnla) on the expression of transporters involved in modulating concentrations of peripheral cholesterol and plasma high-density lipoprotein (HDL) cholesterol. High levels of blood cholesterol are a well-recognized risk factor for atherosclerosis and are eliminated via the process of reverse cholesterol transport (RCT). We recently showed that Retnla ameliorates hypercholesterolemia and atherosclerosis by increasing biliary cholesterol secretion, the final step of the process, in low-density lipoprotein receptor-deficient mice. However, the role of Retnla in HDL-mediated cholesterol efflux, initial step of RCT pathway, is not yet clear. To identify cholesterol transport genes regulated by Retnla, we performed an extensive microarray-based gene expression screen using livers from Retnla-overexpressing (Tg) mice and control animals. The most significant change in Retnla-Tg mice was an upregulation of ATP-binding cassette sub-family G member 4 (Abcg4) transport and was validated using quantitative RT-PCR. The validated gene was also induced by treatment of purified Retnla protein in RAW 264.7 cells incubated with acetylated low-density lipoprotein and Hepa1c1c7 cells. Taken together, these results indicates that Retnla might also accelerate initial step of RCT pathway, suggesting therapeutic value of Retnla in the treatment of hypercholesterolemia and atherosclerosis.

• Journal of Korean Biological Nursing Science
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• v.20 no.2
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• pp.55-66
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• 2018

Purpose: Peripheral neuropathy is common among colorectal cancer (CRC) patients who undergo oxaliplatin-based (OXL) chemotherapy. A pharmacogenetic approach can be used to identify patients at high-risk of developing severe neuropathy. This type of approach can also help clinicians determine the best treatment option and prevent severe neurotoxicity. The purpose of this study is to investigate the evidence of pharmacogenetic markers for OXL-induced peripheral neuropathy (OXIPN) in patients with CRC. Methods: A systematic literature search was conducted using the following databases up to December 2017: Pubmed, EMBASE, and CINAHL. We reviewed the genetic risk factors for OXIPN in observational studies and randomized controlled clinical trials (RCTs). All processes were performed independently by two reviewers. Results: Sixteen studies published in English between 2006 and 2017 were included in this review. A genome-wide association approach was used in one study and various candidate genes were tested, based on their functions (e.g., DNA damage or repair, ion channels, anti-oxidants, and nerve growth etc.). The genes associated with incidence or severity of OXIPN were ABCG2, GSTP1, XRCC1, TAC1, and ERCC1. Conclusion: This study highlighted the need and the importance of conducting pharmacogenetic studies to generate evidence of personalized OXIPN symptoms management. Additional studies are warranted to accelerate the tailored interventions used for OXIPN in patients with CRC (NRF-2014R1A1A3054386).

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.5
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• pp.1931-1936
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• 2014

Background: Gastric cancer (GC) ranks as one of the major causes of mortality due to cancer worldwide. In Chile, it is currently the leading cause of cancer death. Identification of novel molecular markers that may help to improve disease diagnosis at early stages is imperative. Materials and Methods: Using whole-genome DNA microarrays we determined differential mRNA levels in fresh human GC samples compared to adjacent healthy mucosa from the same patients. Genes significantly overexpressed in GC were validated by RT-PCR in a group of 14 GC cases. Results: The genes CD248, NSD1, RAB17, ABCG8, Ephb1 and P2RY2 were detected as the top overexpressed in GC biopsies. P2RY2, Ephb1 and CD248 showed the best sensitivity for GC detection with values of 92.9%, 85.7% and 64.3% (p<0.05), respectively. Specificity was 85.7%, 71.4% and 71.4% (p<0.05), for each respectively.

• The Journal of Korean Medicine
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• v.38 no.2
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• pp.53-60
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• 2017

Objectives: Beakdugu-tang (BDGT) consists of three medicinal herbs, and this prescription has long been used in treatment of various digestant problem in Korea. In this study, we designed to clarify mechanisms by which Korean traditional digestive medicine, BDGT, may exert anti-hepatic steatosis effects via improved insulin resistance cell model in human hepatocellular carcinoma (HepG2) and monocyte (THP-1). Materials and methods: The preparation of BDGT and constituents were extracted with 70% ethanol. HepG2 and THP-1 were treated with different concentrations of BDGT and constituents in the presence and absence of stimulants such as free fatty acids (FFAs) and oxidized low-density lipoprotein (ox-LDL), respectively. Results: The BDGT and its constituents inhibited the FFAs-stimulated lipid accumulation in HepG2 cells. Ethanol extracts of Amomum cardamomum (ACE) improved the ox-LDL induced insulin resistance in THP-1 cells. Also, treatment of monocytic cells with ACE increased anti-hepatic steatosis related gene levels including ABCA, ABCG and SR-B1. Conclusion: The results suggest that the ethanol extract of BDGT and its constituents potently inhibit the FFAs- and ox-LDL induced liver steatosis via improved insulin resistance.

• BMB Reports
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• v.54 no.3
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• pp.170-175
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• 2021

Atherosclerosis arising from the pro-inflammatory conditions associated with chronic kidney disease (CKD) increases major cardiovascular morbidity and mortality. Rapamycin (RAPA) is known to inhibit atherosclerosis under CKD and non-CKD conditions, but it can cause dyslipidemia; thus, the co-application of lipid-lowering agents is recommended. Atorvastatin (ATV) has been widely used to reduce serum lipids levels, but its synergistic effect with RAPA in CKD remains unclear. Here, we analyzed the effect of their combined treatment on atherosclerosis stimulated by CKD in apolipoprotein E-deficient (ApoE-/-) mice. Oil Red O staining revealed that treatment with RAPA and RAPA＋ ATV, but not ATV alone, significantly decreased the atherosclerotic lesions in the aorta and aortic sinus, compared to those seen in the control (CKD) group. The co-administration of RAPA and ATV improved the serum lipid profile and raised the expression levels of proteins involved in reverse cholesterol transport (LXRα, CYP7A1, ABCG1, PPARγ, ApoA1) in the liver. The CKD group showed increased levels of various genes encoding atherosclerosispromoting cytokines in the spleen (Tnf-α, Il-6 and Il-1β) and aorta (Tnf-α and Il-4), and these increases were attenuated by RAPA treatment. ATV and RAPA＋ATV decreased the levels of Tnf-α and Il-1β in the spleen, but not in the aorta. Together, these results indicate that, in CKD-induced ApoE-/- mice, RAPA significantly reduces the development of atherosclerosis by regulating the expression of inflammatory cytokines and the co-application of ATV improves lipid metabolism.

• Biomolecules & Therapeutics
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• v.25 no.5
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• pp.490-496
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• 2017

Imatinib resistance has become a major clinical problem for chronic myeloid leukemia. The aim of the present study was to investigate the involvement of MEG3, a lncRNA, in imatinib resistance and demonstrate its underlying mechanisms. RNAs were extracted from CML patients' peripheral blood cells and human leukemic K562 cells, and the expression of MEG3 was measured by RT-qPCR. Cell proliferation and cell apoptosis were evaluated. Western blotting was used to measure the protein expression of several multidrug resistant transporters. Luciferase reporter assay was performed to determine the binding between MEG3 and miR-21. Our results showed that MEG3 was significantly decreased in imatinib-resistant CML patients and imatinib-resistant K562 cells. Overexpression of MEG3 in imatinib-resistant K562 cells markedly decreased cell proliferation, increased cell apoptosis, reversed imatinib resistance, and reduced the expression of MRP1, MDR1, and ABCG2. Interestingly, MEG3 binds to miR-21. MEG3 and miR-21 were negatively correlated in CML patients. In addition, miR-21 mimics reversed the phenotype of MEG3-overexpression in imatinib-resistant K562 cells. Taken together, MEG3 is involved in imatinib resistance in CML and possibly contributes to imatinib resistance through regulating miR-21, and subsequent cell proliferation, apoptosis and expression of multidrug resistant transporters.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.7
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• pp.3219-3226
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• 2014

Chemotherapy continues to be a mainstay of cancer treatment, although drug resistance is a major obstacle. Lipid metabolism plays a critical role in cancer pathology, with elevated ether lipid levels. Recently, alkylglyceronephosphate synthase (AGPS), an enzyme that catalyzes the critical step in ether lipid synthesis, was shown to be up-regulated in multiple types of cancer cells and primary tumors. Here, we demonstrated that silencing of AGPS in chemotherapy resistance glioma U87MG/DDP and hepatic carcinoma HepG2/ADM cell lines resulted in reduced cell proliferation, increased drug sensitivity, cell cycle arrest and cell apoptosis through reducing the intracellular concentration of lysophosphatidic acid (LPA), lysophosphatidic acid-ether (LPAe) and prostaglandin E2 (PGE2), resulting in reduction of LPA receptor and EP receptors mediated PI3K/AKT signaling pathways and the expression of several multi-drug resistance genes, like MDR1, MRP1 and ABCG2. ${\beta}$-catenin, caspase-3/8, Bcl-2 and survivin were also found to be involved. In summary, our studies indicate that AGPS plays a role in cancer chemotherapy resistance by mediating signaling lipid metabolism in cancer cells.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.3
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• pp.761-766
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• 2012

Objective: Although various human cancer stem cells (CSCs) have been defined, their applications are restricted to immunocompromised models. Developing a novel CSC model which could be used in immunocompetent or transgenic mice is essential for further understanding of the biomolecular characteristics of tumor stem cells. Therefore, in this study, we analyzed murine lung cancer cells for the presence of CSCs. Methods: Side population (SP) cells were isolated by fluorescence activated cell sorting, followed by serum-free medium (SFM) culture, using Lewis lung carcinoma cell (LLC) line. The self-renewal, differentiated progeny, chemosensitivity, and tumorigenic properties in SP and non-SP cells were investigated through in vitro culture and in vivo serial transplantation. Differential expression profiles of stem cell markers were examined by RT-PCR. Results: The SP cell fraction comprised 1.1% of the total LLC population. SP cells were available to grow in SFM, and had significantly enhanced capacity for cell proliferation and colony formation. They were also more resistant to cisplatin in comparison to non-SP cells, and displayed increased tumorigenic ability. Moreover, SP cells showed higher mRNA expression of Oct-4, ABCG2, and CD44. Conclusion: We identified SP cells from a murine lung carcinoma, which possess well-known characteristics of CSCs. Our study established a useful model that should allow investigation of the biological features and pharmacosensitivity of lung CSCs, both in vitro and in syngeneic immunocompetent or transgenic/knockout mice.