• Biomolecules & Therapeutics
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• v.30 no.3
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• pp.274-283
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• 2022

KRAS activating mutations, which are present in more than 90% of pancreatic cancers, drive tumor dependency on the RAS/mitogen-activated protein kinase (MAPK) and phosphoinositide 3-kinase (PI3K)/AKT signaling pathways. Therefore, combined targeting of RAS/MAPK and PI3K/AKT signaling pathways may be required for optimal therapeutic effect in pancreatic cancer. However, the therapeutic efficacy of combined MAPK and PI3K/AKT signaling target inhibitors is unsatisfactory in pancreatic cancer treatment, because it is often accompanied by MAPK pathway reactivation by PI3K/AKT inhibitor. Therefore, we developed an inRas37 antibody, which directly targets the intra-cellularly activated GTP-bound form of oncogenic RAS mutation and investigated its synergistic effect in the presence of the PI3K inhibitor BEZ-235 in pancreatic cancer. In this study, inRas37 remarkably increased the drug response of BEZ-235 to pancreatic cancer cells by inhibiting MAPK reactivation. Moreover, the co-treatment synergistically inhibited cell proliferation, migration, and invasion and exhibited synergistic anticancer activity by inhibiting the MAPK and PI3K pathways. The combined administration of inRas37and BEZ-235 significantly inhibited tumor growth in mouse models. Our results demonstrated that inRas37 synergistically increased the antitumor activity of BEZ-235 by inhibiting MAPK reactivation, suggesting that inRas37 and BEZ-235 co-treatment could be a potential treatment approach for pancreatic cancer patients with KRAS mutations.

• Biomedical Science Letters
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• v.21 no.4
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• pp.227-232
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• 2015

Epstein-Barr virus (EBV) has a pathogenic role in several lymphomas including diffuse large B-cell lymphoma (DLBCL). In this study, we detected EBV from formalin-fixed paraffin embedded (FFPE) tissues of DLBCL patients by RT-PCR and compared the sensitivity of the RT-PCR method to in situ hybridization (ISH) method. The RNA was extracted from 91 FFPE samples with DLBCL and amplified with primers targeting EBV-encoded small RNA (EBER) by RT-PCR. When using the RT-PCR method, 13 of 91 patients (14.3%) were positive and among these 13 cases, 7 cases (7.7%) were from > 50-year-old patients that is classified as EBV positive DLBCL of the elderly. In previous results using ISH method, 3 of 91 patients (3.3%) were positive and 2 case (2.4%) were older than 50-year-old. These results indicate that RT-PCR method used in this study shows a higher sensitivity than ISH method. The ratio of male versus female among the EBV positive samples was 1.2:1 with the ratio of male higher. If RT-PCR method having high sensitivity is used simultaneously as well as the ISH method providing the information of the EBV positive cellular location, it is expected that EBV will be more accurately detected.

• Molecules and Cells
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• v.46 no.11
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• pp.725-725
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• 2023

• Proceedings of the Korean Nutrition Society Conference
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• 2003.10a
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• pp.164-164
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• 2003

• Biomedical Science Letters
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• v.25 no.2
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• pp.185-189
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• 2019

Breast cancer is the second most common cancer in women with approximately 522,000 deaths annually worldwide. microRNAs have recently been studied as potential biomarkers that regulate gene expression and are involved in tumorigenesis. Here we evaluated circulating miR-221 and miR-222 as potential biomarkers for breast cancer by quantitative reverse transcription PCR using blood plasma of 30 healthy controls and 30 breast cancer patients. The TNM stage on circulating miR-221 and miR-222 was also investigated. Circulating miR-221 and miR-222 were significantly up-regulated in breast cancer patients compared to those in healthy controls (P < 0.0022 and P = 0.0058, respectively). Furthermore, the relative expression level of circulating miR-221 in patients with stage III breast cancer was higher than in those with stage I and II. Taken together, we have shown circulating miR-221 and miR-222 could be useful biomarkers for the screening of breast cancer patients.

• Biomedical Science Letters
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• v.16 no.1
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• pp.10-18
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• 2010

The present study was set to develop comprehensive system for assessing the safety of drinking water using PCR-reverse blot hybridization assay (REBA). The REBA developed in this study can detect waterborne pathogens such as Shigella spp., Salmonella spp., Citrobacter spp., Enterobacter spp., Klebsiella spp., Yersinia spp., Mycobacterium spp., Listeria spp. at the genus level, and Escherichia coli, Citrobacter freundii, Klebsiella pneumoniae, Pseudomonas aeruginosa, Yersinia enterocolitica, Y. pseudotuberculosis, Mycobacterium avium complex, M. marinum, Enterococcus faecalis, and Staphylococcus aureus at the species level, and E. coli O157:H7 at the strain level.

• Biomedical Science Letters
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• v.19 no.1
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• pp.9-16
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• 2013

Elevated blood triglyceride (TG) levels correlate with development of atherosclerosis suggesting that TG may promote the development of this disease. During atherosclerosis, TG is taken up by tissue macrophages which result in dramatic changes in various secreted factors. One such factor is the family of matrix metalloproteases (MMP) which are involved in tissue remodeling during both physiological and pathological processes. In this study, we examined the MMP expression profile in PMA-differentiated THP-1 macrophages treated with TG. We found that TG-treated THP-1 macrophages showed decreased expression of MMP-3, MMP-7, MMP-8 and MMP-9 in a time- and dose-dependent manner. In contrast, expression of MMP-1, MMP-2, and MMP-10 remained relatively unchanged after TG treatment. In addition, we found that expression of select MMPs was affected by various inhibitors of signaling pathways. In particular, expression of MMP-3 was slightly recovered by cRAF and PLC signaling pathway inhibitors. These data suggests a possible role of MMPs in macrophages during TG-induced atherosclerosis.

• Biomedical Science Letters
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• v.25 no.3
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• pp.267-274
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• 2019

Toll-like receptors (TLRs) are one of the families of pattern recognition receptors (PRR) to recognize pathogen-associated molecular patterns (PAMPs). PAMPs stimulate TLRs to initiate specific immunoactivity. The activation of TLRs signaling leads to the expression of pro-inflammatory gene products such as cytokines and inducible nitric oxide synthase (iNOS). To evaluate the therapeutic potential of dehydrocostus lactone (DHL), which is a natural sesquiterpene lactone derived from various medicinal plants, iNOS expression induced by LPS (TLR4 agonist), MALP-2 (TLR2 and TLR6 agonist), or Poly[I:C] (TLR3 agonist) were examined. DHL suppressed the iNOS expression induced by LPS, MALP-2, or Poly[I:C]. DHL also inhibited nitrite production induced by LPS, MALP-2, or Poly[I:C]. These results suggest that DHL can modulate TLRs signaling pathways resulting in anti-inflammatory effect.

• Biomedical Science Letters
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• v.28 no.3
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• pp.206-210
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• 2022

Calystegia dahurica (Herb.) Choisy is a natural product that has not been studied for efficacy or active ingredients. The purpose of this study is to investigate the activation effect of natural killer cells using a natural extract composition based on Calystegia dahurica (Herb.) Choisy extract (CDCE). We evaluated the activity of natural killer cells in natural products using PBMCs from healthy participants. All natural products were extracted with 50% ethanol. Based on the results of the cell viability assay, PBMCs of healthy participants were treated with extracts at various concentrations. Then, analysis was performed using flow cytometry to measure the cd107a surface expression of natural killer cells. As a result, treatment with a single extract of PBMCs increased the expression of cd107a in a concentration-dependent. Furthermore, it was confirmed that the treatment of the extract composition showed the highest expression of cd107a. In conclusion, it is expected that the extract composition containing CDCE according to this study can be used for prevention or treatment of cancer cells, tumor cells, and immune diseases.

• Biomedical Science Letters
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• v.18 no.2
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• pp.123-130
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• 2012

In this study, we evaluated the human papillomavirus (HPV) genotyping test called MolecuTech REBA HPV-$ID^{(R)}$ (YD Diagnostics, Seoul, Korea) for 704 women who also had cervical cytological evaluations by Thin Prep. The infection rate of high-risk HPV genotypes was 56.6% in patients with normal cytology, 59.8% in those with benign, low-grade squamous intraepithelial lesions, 51.4% in those with atypical squamous cells of uncertain significance, 92.3% in those with high-grade squamous intraepithelial lesions, and 94.1% in those with squamous cell carcinoma or adenocarcinoma. HPV 16 was the most common genotype detected in any lesion, followed by HPV 53, 58, 33, 52, 45, 31, and 35, in order. The HPV DNA test with PCR-REBA is a very highly sensitive, but less specific, method. The infection rates and HPV genotype distribution of non-Korean people versus people from South Korea showed regional differences.