• Journal of Korean Traditional Oncology
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• v.21 no.1
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• pp.1-14
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• 2016

The incidence rate of cervical cancer in Korea is still higher than in other developed countries, notwithstanding the national mass screening program. Cervical cancer prognosis is good due to an effective treatment such as surgery or radiation therapy, concurrent chemotherapy in the early stage. However, it is still a poor prognosis when advanced stage or recurrent. Some studies said that combined oriental and western medicine can improve the survival, quality of life, immune function, and decrease side effects in cervical cancer. In the western medical part, clinical practice guideline was published in 2006, 2007 and 2010 in Korea. In China, oriental medicine clinical practice guideline have been published in 2014. But there is no Korean medicine clinical practice guideline. This study will introduce the methods of diagnosis and the medical therapeutics which is commonly utilized for cervical cancer in Korea, and existing Korean medicine clinical practice guideline for Disease Analysis and Treatment (辨證論治). This study will be a meaningful study to establish clinical practice guidelines of Korean Medicine for cervical cancer.

• Biomolecules & Therapeutics
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• v.24 no.2
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• pp.140-146
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• 2016

Naringenin (NAR) as one of the flavonoids observed in grapefruit has been reported to exhibit an anti-cancer activity. Activating transcription factor 3 (ATF3) is associated with apoptosis in human colon cancer cells. This study was performed to investigate the molecular mechanism by which NAR stimulates ATF3 expression and apoptosis in human colon cancer cells. NAR reduced the cell viability and induced an apoptosis in human colon cancer cells. ATF3 overexpression increased NAR-mediated cleaved PARP, while ATF3 knockdown attenuated the cleavage of PARP by NAR. NAR increased ATF3 expression in both protein and mRNA level, and increased the luciferase activity of ATF3 promoter in a dose-dependent manner. The responsible region for ATF3 transcriptional activation by NAR is located between -317 and -148 of ATF3 promoter. p38 inhibition blocked NAR-mediated ATF3 expression, its promoter activation and apoptosis. The results suggest that NAR induces apoptosis through p38-dependent ATF3 activation in human colon cancer cells.

• Bulletin of the Korean Chemical Society
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• v.35 no.12
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• pp.3623-3626
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• 2014

Nuclear factor-erythroid 2-related factor 2 (Nrf2) regulates the expression of over 200 genes of antioxidant and phase II drug-metabolizing enzymes, and is highly expressed in non-small cell lung cancer (NSCLC). Nine derivatives of 4-(2-cyclohexylethoxy)aniline were designed. Our previous study demonstrated that IM3829 increases radiosensitivity of several lung cancer cells in vitro and in vivo. Here, biological effects of IM3829 derivatives (2a-2i) were evaluated. Compound 2g derivative effectively inhibits mRNA and protein expression of Nrf2 and HO-1. In addition, we observed over two fold enhancement in IR-induced cell death, from $2.90{\pm}0.22$ to $6.02{\pm}0.87$, in H1299 cancer cell-line. Among the nine derivatives, compound 2g derivative exhibited the highest enhancement of radiosensitizing effect via inhibition of Nrf2 activity.

• Biomolecules & Therapeutics
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• v.26 no.1
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• pp.4-9
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• 2018

Cancer metabolism as a field of research was founded almost 100 years ago by Otto Warburg, who described the propensity for cancers to convert glucose to lactate despite the presence of oxygen, which in yeast diminishes glycolytic metabolism known as the Pasteur effect. In the past 20 years, the resurgence of interest in cancer metabolism provided significant insights into processes involved in maintenance metabolism of non-proliferating cells and proliferative metabolism, which is regulated by proto-oncogenes and tumor suppressors in normal proliferating cells. In cancer cells, depending on the driving oncogenic event, metabolism is re-wired for nutrient import, redox homeostasis, protein quality control, and biosynthesis to support cell growth and division. In general, resting cells rely on oxidative metabolism, while proliferating cells rewire metabolism toward glycolysis, which favors many biosynthetic pathways for proliferation. Oncogenes such as MYC, BRAF, KRAS, and PI3K have been documented to rewire metabolism in favor of proliferation. These cell intrinsic mechanisms, however, are insufficient to drive tumorigenesis because immune surveillance continuously seeks to destroy neo-antigenic tumor cells. In this regard, evasion of cancer cells from immunity involves checkpoints that blunt cytotoxic T cells, which are also attenuated by the metabolic tumor microenvironment, which is rich in immuno-modulating metabolites such as lactate, 2-hydroxyglutarate, kynurenine, and the proton (low pH). As such, a full understanding of tumor metabolism requires an appreciation of the convergence of cancer cell intrinsic metabolism and that of the tumor microenvironment including stromal and immune cells.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.4
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• pp.1671-1674
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• 2015

Cancer genomics and proteomics have undergone considerable broadening in the past decades and increasingly it is being realized that solid/liquid phase microarrays and high-throughput resequencing have provided platforms to improve our existing knowledge of determinants of cancer development, progression and survival. Loss of apoptosis is a widely and deeply studied process and different approaches are being used to restore apoptosis in resistant cancer phenotype. Modulating the balance between pro-apoptotic and anti-apoptotic proteins is essential to induce apoptosis. It is becoming more understood that pharmacological inhibition of the proteasome might prove to be an effective option in improving TRAIL induced apoptosis in cancer cells. Keeping in view rapidly accumulating evidence of carcinogenesis, metastasis, resistance against wide ranging therapeutics and loss of apoptosis, better knowledge regarding tumor suppressors, oncogenes, pro-apoptotic and anti-apotptic proteins will be helpful in translating the findings from benchtop to bedside.

• Biomolecules & Therapeutics
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• v.24 no.1
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• pp.62-66
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• 2016

Amygdalin, D-mandelonitrile-${\beta}$-D-glucoside-6-${\beta}$-glucoside, belongs to aromatic cyanogenic glycoside group derived from rosaceous plant seed. Mounting evidence has supported the anti-cancer effects of amygdalin. However, whether amygdalin indeed acts as an anti-tumor agent against breast cancer cells is not clear. The present study aimed to investigate the effect of amygdalin on the proliferation of human breast cancer cells. Here, we show that amygdalin exerted cytotoxic activities on estrogen receptors (ER)-positive MCF7 cells, and MDA-MB-231 and Hs578T triple-negative breast cancer (TNBC) cells. Amygdalin induced apoptosis of Hs578T TNBC cells. Amygdalin downregulated B-cell lymphoma 2 (Bcl-2), upregulated Bcl-2-associated X protein (Bax), activated of caspase-3 and cleaved poly ADP-ribose polymerase (PARP). Amygdalin activated a pro-apoptotic signaling molecule p38 mitogen-activated protein kinases (p38 MAPK) in Hs578T cells. Treatment of amygdalin significantly inhibited the adhesion of Hs578T cells, in which integrin ${\alpha}5$ may be involved. Taken together, this study demonstrates that amygdalin induces apoptosis and inhibits adhesion of breast cancer cells. The results suggest a potential application of amygdalin as a chemopreventive agent to prevent or alleviate progression of breast cancer, especially TNBC.

• Biomolecules & Therapeutics
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• v.23 no.4
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• pp.301-312
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• 2015

Metastasis is one of hallmarks of cancer and a major cause of cancer death. Combatting metastasis is highly challenging. To overcome these difficulties, researchers have focused on physical properties of metastatic cancer cells. Metastatic cancer cells from patients are softer than benign cancer or normal cells. Changes of viscoelasticity of cancer cells are related to the keratin network. Unexpectedly, keratin network is dynamic and regulation of keratin network is important to the metastasis of cancer. Keratin is composed of heteropolymer of type I and II. Keratin connects from the plasma membrane to nucleus. Several proteins including kinases, and protein phosphatases bind to keratin intermediate filaments. Several endogenous compounds or toxic compounds induce phosphorylation and reorganization of keratin network in cancer cells, leading to increased migration. Continuous phosphorylation of keratin results in loss of keratin, which is one of the features of epithelial mesenchymal transition (EMT). Therefore, several proteins involved in phosphorylation and reorganization of keratin also have a role in EMT. It is likely that compounds controlling phosphorylation and reorganization of keratin are potential candidates for combating EMT and metastasis.

• Anatomy and Cell Biology
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• v.56 no.1
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• pp.94-108
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• 2023

Cancer cell heterogeneity is a serious problem in the control of tumor progression because it can cause chemoresistance and metastasis. Heterogeneity can be generated by various mechanisms, including genetic evolution of cancer cells, cancer stem cells (CSCs), and niche heterogeneity. Because the genetic heterogeneity of CSCs has been poorly characterized, the genetic mutation status of CSCs was examined using Exome-Seq and RNA-Seq data of liver cancer. Here we show that different surface markers for liver cancer stem cells (LCSCs) showed a unique propensity for genetic mutations. Cluster of differentiation 133 (CD133)-positive cells showed frequent mutations in the IRF2, BAP1, and ERBB3 genes. However, leucine-rich repeat-containing G protein-coupled receptor 5-positive cells showed frequent mutations in the CTNNB1, RELN, and ROBO1 genes. In addition, some genetic mutations were frequently observed irrespective of the surface markers for LCSCs. BAP1 mutations was frequently observed in CD133-, CD24-, CD13-, CD90-, epithelial cell adhesion molecule-, or keratin 19-positive LCSCs. ASXL2, ERBB3, IRF2, TLX3, CPS1, and NFATC2 mutations were observed in more than three types of LCSCs, suggesting that common mechanisms for the development of these LCSCs. The present study provides genetic heterogeneity depending on the surface markers for LCSCs. The genetic heterogeneity of LCSCs should be considered in the development of LCSC-targeting therapeutics.

• Biomolecules & Therapeutics
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• v.23 no.6
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• pp.493-509
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• 2015

Antibody-drug conjugates utilize the antibody as a delivery vehicle for highly potent cytotoxic molecules with specificity for tumor-associated antigens for cancer therapy. Critical parameters that govern successful antibody-drug conjugate development for clinical use include the selection of the tumor target antigen, the antibody against the target, the cytotoxic molecule, the linker bridging the cytotoxic molecule and the antibody, and the conjugation chemistry used for the attachment of the cytotoxic molecule to the antibody. Advancements in these core antibody-drug conjugate technology are reflected by recent approval of Adectris$^{(R)}$(anti-CD30-drug conjugate) and Kadcyla$^{(R)}$(anti-HER2 drug conjugate). The potential approval of an anti-CD22 conjugate and promising new clinical data for anti-CD19 and anti-CD33 conjugates are additional advancements. Enrichment of antibody-drug conjugates with newly developed potent cytotoxic molecules and linkers are also in the pipeline for various tumor targets. However, the complexity of antibody-drug conjugate components, conjugation methods, and off-target toxicities still pose challenges for the strategic design of antibody-drug conjugates to achieve their fullest therapeutic potential. This review will discuss the emergence of clinical antibody-drug conjugates, current trends in optimization strategies, and recent study results for antibody-drug conjugates that have incorporated the latest optimization strategies. Future challenges and perspectives toward making antibody-drug conjugates more amendable for broader disease indications are also discussed.

• International Journal of Oral Biology
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• v.44 no.2
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• pp.43-49
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• 2019

Tannic acid (TA) is a water-soluble polyphenol compound found in various herbal plants. We investigated the chemopreventive effects of TA on FaDu hypopharyngeal squamous carcinoma cells. In an 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, TA showed dose-dependent cytotoxicity with a half maximal inhibitory concentration (IC50) of 50 ?M. Cell cycle analysis and immunofluorescence imaging demonstrated that under low-dose ($25{\mu}M$) treatment, FaDu cells were arrested in G2/M phase, and as the dose of TA was increased, apoptosis was induced with the increase of cell population at sub-G1 phase. The expressions of various cyclins, including cyclin D1 and cyclin-dependent kinases (CDK-1 and CDK-2), were down-regulated at low doses of TA, whereas apoptotic effectors such as cleaved caspase 3, cleaved caspase 7, and poly (ADP-ribose) polymerase (PARP) were expressed in a dose-dependent manner in Western blotting. In addition, TA-induced apoptosis of FaDu cells might be mediated by the extracellular signal-regulated kinase (ERK)/mitogen-activated protein kinase pathway, with the upregulation of p-AKT/p-PKB (phosphorylated protein kinase B) and p-ERK. Overall, our data support the hypothesis that TA is a potential candidate agent for the treatment of hypopharyngeal cancer.