• YAKHAK HOEJI
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• v.55 no.1
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• pp.16-21
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• 2011

HER-2 (Human Epidermal Growth Factor Receptor-2) is a protein giving higher aggressiveness in human breast cancers. Trastuzumab is a monoclonal antibody that targets HER-2 and is known to extend survival across all stages of HER2-positive breast cancer. In this study, we attempted to development of a quantitative ELISA (Enzyme-Linked ImmunoSorbent Assay) for evaluating anti HER-2 antibodies using human HER-2 recombinant proteins to support antibody producing processes and pharmacokinetic studies. We established direct or indirect ELISA method for the trastuzumab-like protein combined human recombinant HER-2. The ELISA method will prove to be great value in quantitating anti-HER-2 antibodies levels for developing anticancer antibodies.

• Tuberculosis and Respiratory Diseases
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• v.62 no.2
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• pp.144-148
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• 2007

Gefitinib is an oral selective inhibitor that targets the tyrosine kinase of the epidermal growth factor receptor. The prevalence of interstitial lung disease is 2% in Japan and 0.3% in the USA with a mortality rate of up to one third. We describe two non-small cell lung cancer patients who developed acute respiratory failure after gefitinib, and suggest that clinicians take extreme caution when deciding to treat patients with gefitinib.

• Bulletin of the Korean Chemical Society
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• v.30 no.8
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• pp.1827-1831
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• 2009

Ligand molecules that can recognize and interact with cancer cell surface marker proteins with high affinity and specificity should greatly aid the development of novel cancer diagnostics and therapeutics. HER-2/ErbB2/Neu (HER-2), a member of the epidermal growth factor receptor family, is specifically overexpressed on the surface of breast cancer cells and serves as both a useful biomarker and a therapeutic target for breast cancer. In this study, we aimed to isolate RNA aptamers that specifically bind to a HER-2-overexpressing human breast cancer cell line, SK-BR-3, using Cell-SELEX strategy. The selected aptamers showed strong affinity to SK-BR-3, but not to MDAMB- 231, a HER-2-underexpressing breast cancer cell line. In addition, we confirmed the specific targeting of HER-2 receptor by aptamers using an unrelated mouse cell line overexpressing human HER-2 receptor. The HER-2-targeting RNA aptamers could become a useful reagent for the development of breast cancer diagnostics and therapeutics.

• BMB Reports
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• v.51 no.3
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• pp.119-125
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• 2018

The Hippo pathway plays prominent and widespread roles in various forms of human carcinogenesis. Specifically, the Yes-associated protein (YAP), a downstream effector of the Hippo pathway, can lead to excessive cell proliferation and the inhibition of apoptosis, resulting in tumorigenesis. It was reported that the YAP is strongly elevated in multiple types of human malignancies such as breast, lung, small intestine, colon, and liver cancers. Recent work indicates that, surprisingly, Hippo signaling components' (SAV1, MST1/2, Lats1/2) mutations are virtually absent in human cancer, rendering this signaling an unlikely candidate to explain the vigorous activation of the YAP in most, if not all human tumors and an activated YAP promotes the resistance to RAF-, MAPK/ERK Kinase (MEK)-, and Epidermal growth factor receptor (EGFR)-targeted inhibitor therapy. The analysis of YAP expressions can facilitate the identification of patients who respond better to an anti-cancer drug treatment comprising RAF-, MEK-, and EGFR-targeted inhibitors. The prominence of YAP for those aspects of cancer biology denotes that these factors are ideal targets for the development of anti-cancer medications. Therefore, our report strongly indicates that the YAP is of potential prognostic utility and druggability in various human cancers.

• BMB Reports
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• v.51 no.1
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• pp.27-32
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• 2018

Non-small-cell lung cancer (NSCLC) is commonly caused by a mutation in the epidermal growth factor receptor (EGFR) and subsequent aberrant EGFR signaling with uncontrolled kinase activity. A deletion mutation in EGFR exon 19 is frequently observed in EGFR gene mutations. We designed a DNAzyme to suppress the expression of mutant EGFR by cleaving the mutant EGFR mRNA. The DNAzyme (named Ex19del Dz) specifically cleaved target RNA and decreased cancer cell viability when transfected into gefitinib-resistant lung cancer cells harboring EGFR exon 19 deletions. The DNAzyme decreased EGFR expression and inhibited its downstream signaling pathway. In addition to EGFR downregulation, Ex19del Dz containing CpG sites activated Toll-like receptor 9 (TLR9) and its downstream signaling pathway via p38 kinase, causing an immunostimulatory effect on EGFR-mutated NSCLC cells. Thus, dual effects of this DNAzyme harboring the CpG site, such as TLR9 activation and EGFR downregulation, leads to apoptosis of EGFR-mutated NSCLC cells.

• YAKHAK HOEJI
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• v.41 no.6
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• pp.730-736
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• 1997

Distribution of radioactivity in the skin tissues, subcutaneous tissues, blood and body organs was examined following topical application of $^{125}I-rhEGF$(0.4 ${\mu}Ci$), in the form of a Pluronic F-127 gel, on the normal and damaged (burned and stripped) skins of SD male rats. The radioactivity in the skin tissues and subcutaneous tissues was 3-5 times higher for the damaged skins than for the normal skin. But pretreatment of the skin with rhEGF (1${\mu}g$)) twice at 24 hr dose intervals affected the distribution of the radioactivity yielding the order of burned skin> stripped skin=normal skin. The decrease for the stripped skin by the pretreatment might be related either to the pathophysiological change of the skin or to the down regulation of the EGF receptor. Liver showed the highest radioactivity in amount following single and multiple administration of the drug to the normal and damaged skins. But,in concentration, the kidney and stomach showed higher value than the liver which is consistent with that kidney is a major eliminating organ of EGF and that EGF exerts its pharmacological effect specifically for the stomach.

• Journal of Yeungnam Medical Science
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• v.35 no.1
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• pp.99-103
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• 2018

Mammary Paget's disease (MPD) is usually accompanied by underlying breast malignancy; however, a few cases have been reported as only skin lesions without any evidence of malignancy of the breast on imaging tests and microscopic examination of surgical specimen. Here, we describe a 47-year-old woman who visited our hospital who had an eczematous lesion on right nipple and areola for over 10 years. The lesion was diagnosed as Paget's disease by punch biopsy; however, imaging studies demonstrated no breast malignancy or lymph node metastasis. The patient underwent surgery of on the nipple and areola including underlying breast tissue. No underlying malignancy was found upon microscopic examination, except for Paget's disease. Immunohistochemical stains revealed that the tumor cells were positive for cytokeratin 7, and negativity for p63, cytokeratin 5/6, estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2. We report a case of MPD without underlying malignancy. To the best of our knowledge, this is the third case reported in Korea.

• Korean Journal of Clinical Oncology
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• v.14 no.2
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• pp.108-115
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• 2018

Purpose: This study aimed to compare the results of treatment with adjuvant trastuzumab for 9 months versus 12 months in human epidermal growth factor 2 (HER2)-positive breast cancer patients. The primary endpoint was disease-free survival. Secondary endpoints included cardiac safety, tolerability, and overall survival. Methods: The study included 60 non-metastatic HER2-positive breast cancer patients. All study patients underwent surgery, received adjuvant chemotherapy, radiotherapy and hormonal therapy if indicated. Thirty patients were randomized in each group. Group I patients received adjuvant trastuzumab for 12 months, while group II patients received adjuvant trastuzumab for 9 months. Patients were assessed by clinical examination and Echocardiography during treatment. Results: After median follow-up of 12 months, 90% of the patients in group I were disease free and 83.3% of patients in group II were disease free (P=0.402). All studied population in both groups I and II were alive at the end of the 1-year follow-up period after the completion of adjuvant trastuzumab treatment thus overall survival is 100%. Conclusion: Trastuzumab is tolerable and its side effects are reversible. Nine months of adjuvant trastuzumab treatment is more cost effective than the standard 12 months.

• Parasites, Hosts and Diseases
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• v.57 no.4
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• pp.445-450
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• 2019

Human infections due to the monkey malaria parasite Plasmodium knowlesi is increasingly being reported from most Southeast Asian countries specifically Malaysia. The parasite causes severe and fatal malaria thus there is a need for urgent measures for its control. In this study, the level of polymorphisms, haplotypes and natural selection of full-length pkmsp8 in 37 clinical samples from Malaysian Borneo along with 6 lab-adapted strains were investigated. Low levels of polymorphism were observed across the full-length gene, the double epidermal growth factor (EGF) domains were mostly conserved, and non-synonymous substitutions were absent. Evidence of strong negative selection pressure in the non-EGF regions were found indicating functional constrains acting at different domains. Phylogenetic haplotype network analysis identified shared haplotypes and indicated geographical clustering of samples originating from Peninsular Malaysia and Malaysian Borneo. This is the first study to genetically characterize the full-length msp8 gene from clinical isolates of P. knowlesi from Malaysia; however, further functional characterization would be useful for future rational vaccine design.

• Biomedical Science Letters
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• v.25 no.1
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• pp.23-31
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• 2019

The protein kinase $CK2{\alpha}$ (formerly Casein Kinase II) is implicated in tumorigenesis and transformation. However, the mechanisms of $CK2{\alpha}$ activation in breast cancer have yet to be elucidated. This study investigated the mechanisms of $CK2{\alpha}$ activation in estrogen signaling. Estrogen increased reactive oxygen species (ROS) production, $CK2{\alpha}$ activity, and protein expression in estrogen receptor positive ($ER^+$) MCF-7 human breast cancer cells, which were inhibited by the antioxidant N-acetyl-L-cysteine. $H_2O_2$ enhanced $CK2{\alpha}$ activity and protein expression. Human epidermal growth factor (EGF) increased ROS production, $CK2{\alpha}$ activity and protein expression in EGF receptor 2 (HER2)-overexpressing MCF-7 (MCF-7 HER2) cells, but not in MCF-7 cells. Estrogen induced the phosphorylation of p38 mitogen-activated protein kinase (MAPK). The p38 inhibitor, SB202190, blocked estrogen-induced increases in ROS production, $CK2{\alpha}$ activity and $CK2{\alpha}$ protein expression. The data suggest that ROS/p38 MAPK is the key inducer of $CK2{\alpha}$ activation in response to estrogen or EGF.