• BMB Reports
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• v.53 no.12
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• pp.628-633
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• 2020

WNT11 is a member of the non-canonical Wnt family and plays a crucial role in tumor progression. However, the regulatory mechanisms underlying WNT11 expression are unclear. Tumor necrosis factor-alpha (TNFα) is a major inflammatory cytokine produced in the tumor microenvironment and contributes to processes associated with tumor progression, such as tumor invasion and metastasis. By using site-directed mutagenesis and introducing a serial deletion in the 5'-regulatory region of WNT11, we observed that TNFα activates the early growth response 1 (EGR1)-binding sequence (EBS) in the proximal region of WNT11 and that the transcription factor EGR1 is necessary for the TNFα-induced transcription of WNT11. EGR1 bound directly to the EBSs within the proximal 5'-regulatory region of WNT11 and ectopic expression of EGR1 stimulated WNT11 promoter activity, whereas the knockdown of EGR1 expression by RNA interference reduced TNFα-induced WNT11 expression in T47D breast cancer cells. We also observed that mitogen-activated protein kinases (MAPK), extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and p38 kinase mediated TNFα-induced transcription of WNT11 via EGR1. Our results suggest that EGR1 directly targets WNT11 in response to TNFα stimulation in breast cancer cells.

• Molecules and Cells
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• v.45 no.6
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• pp.413-424
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• 2022

Suppressor of mothers against decapentaplegic homolog (SMAD) 4 is a pluripotent signaling mediator that regulates myriad cellular functions, including cell growth, cell division, angiogenesis, apoptosis, cell invasion, and metastasis, through transforming growth factor β (TGF-β)-dependent and -independent pathways. SMAD4 is a critical modulator in signal transduction and functions primarily as a transcription factor or cofactor. Apart from being a DNA-binding factor, the additional SMAD4 mechanisms in tumor suppression remain elusive. We previously identified methyl malonyl aciduria cobalamin deficiency B type (MMAB) as a critical SMAD4 binding protein using a proto array analysis. This study confirmed the interaction between SMAD4 and MMAB using bimolecular fluorescence complementation (BiFC) assay, proximity ligation assay (PLA), and conventional immunoprecipitation. We found that transient SMAD4 overexpression down-regulates MMAB expression via a proteasome-dependent pathway. SMAD4-MMAB interaction was independent of TGF-β signaling. Finally, we determined the effect of MMAB downregulation on cancer cells. siRNA-mediated knockdown of MMAB affected cancer cell metabolism in HeLa cells by decreasing ATP production and glucose consumption as well as inducing apoptosis. These findings suggest that SMAD4 controls cancer cell metabolism by regulating MMAB.

• BMB Reports
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• v.55 no.6
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• pp.281-286
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• 2022

Hepatocellular carcinoma is a major health burden, and though various treatments through much research are available, difficulties in early diagnosis and drug resistance to chemotherapy-based treatments render several ineffective. Cancer stem cell model has been used to explain formation of heterogeneous cell population within tumor mass, which is one of the underlying causes of high recurrence rate and acquired chemoresistance, highlighting the importance of CSC identification and understanding the molecular mechanisms of CSC drivers. Extracellular CSC-markers such as CD133, CD90 and EpCAM have been used successfully in CSC isolation, but studies have indicated that increasingly complex combinations are required for accurate identification. Pseudogene-derived long non-coding RNAs are useful candidates as intracellular CSC markers - factors that regulate pluripotency and self-renewal - given their cancer-specific expression and versatile regulation across several levels. Here, we present the use of microarray data to identify stemness-associated factors in liver cancer, and selection of sole pseudogene-derived lncRNA ZNF204P for experimental validation. ZNF204P knockdown impairs cell proliferation and migration/invasion. As the cytosolic ZNF204P shares miRNA binding sites with OCT4 and SOX2, well-known drivers of pluripotency and self-renewal, we propose that ZNF204P promotes tumorigenesis through the miRNA-145-5p/OCT4, SOX2 axis.

• Journal of Dental Anesthesia and Pain Medicine
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• v.24 no.2
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• pp.129-135
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• 2024

Concomitant chemoradiotherapy (CCRT) treated patients experience various complications. We present a rare case of post-CCRT Bell's palsy and describe its various possible causes, so as to increase awareness among clinicians about Bell's palsy being a CCRT-associated adverse effect. The patient was a 48-year-old man diagnosed with squamous cell carcinoma who presented with post-CCRT Bell's palsy. After radiotherapy for 6 weeks (overall 67.5 Gy) and four rounds of cisplatin chemotherapy, he complained of paralysis of the entire left face. A test was performed 33 days after the last CCRT session to differentiate Bell's palsy from other causative factors. Based on magnetic resonance imaging findings, facial nerve invasion due to tumor size increase was determined to not cause Bell's palsy. Inflammation of the left Eustachian tube was observed. Hence, steroids and famciclovir were administered, which markedly improved the facial paralysis symptoms within 56 days after facial paralysis development. In conclusion, patients can develop Bell's palsy owing to complex effects of various CCRT mechanisms. Although the exact cause of Bell's palsy has not been identified and the effectiveness of drug treatment was questionable in this case, unlikely causative factors should be excluded through various tests and appropriate and timely measures must be adopted.

• Molecules and Cells
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• v.39 no.5
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• pp.426-438
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• 2016

Plant disease resistance occurs as a hypersensitive response (HR) at the site of attempted pathogen invasion. This specific event is initiated in response to recognition of pathogen-associated molecular pattern (PAMP) and subsequent PAMP-triggered immunity (PTI) and effector-triggered immunity (ETI). Both PTI and ETI mechanisms are tightly connected with reactive oxygen species (ROS) production and disease resistance that involves distinct biphasic ROS production as one of its pivotal plant immune responses. This unique oxidative burst is strongly dependent on the resistant cultivars because a monophasic ROS burst is a hallmark of the susceptible cultivars. However, the cause of the differential ROS burst remains unknown. In the study here, we revealed the plausible underlying mechanism of the differential ROS burst through functional understanding of the Magnaporthe oryzae (M. oryzae) AVR effector, AVR-Pii. We performed yeast two-hybrid (Y2H) screening using AVR-Pii as bait and isolated rice NADP-malic enzyme2 (Os-NADP-ME2) as the rice target protein. To our surprise, deletion of the rice Os-NADP-ME2 gene in a resistant rice cultivar disrupted innate immunity against the rice blast fungus. Malic enzyme activity and inhibition studies demonstrated that AVR-Pii proteins specifically inhibit in vitro NADP-ME activity. Overall, we demonstrate that rice blast fungus, M. oryzae attenuates the host ROS burst via AVR-Pii-mediated inhibition of Os-NADP-ME2, which is indispensable in ROS metabolism for the innate immunity of rice. This characterization of the regulation of the host oxidative burst will help to elucidate how the products of AVR genes function associated with virulence of the pathogen.

• Development and Reproduction
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• v.11 no.1
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• pp.1-11
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• 2007

Specific endometrial preparation should occur during periimplantation period. That is a progress of serial differentiation and is absolute in implantation of embryo and successful pregnancy. Remodeling of tissues shown during embryogenesis is regulated by various factors including extracellular matrix (ECM). Marked changes during pregnancy are including embryo migration, decidual response, and differentiation of placenta in placental animals including human. These changes to successful implantation in embryo and uterus have to prepare the competence for attachment of embryo and uterus, and invasion defense of uterus. During these changes, ECM dramatically changes for maintaining the uterine and embryonic functions. The major component of most connective tissue is collagens. It is very complex and hard to explore the mechanisms for ECM modulation. Recently using high throughput methodology, PCR-select cDNA subtraction method, microarray, many candidate genes have been identified. Steroid hormones have fundamental role in implantation and maintenance of pregnancy. Dermatopontin, a regulator of collagen accumulation, is regulated spatio-temporally in the uterus by primarily progesterone through progesterone receptors at the time of implantation. Modulation of extracellular matrix is critically regulated by cascade of gene net-works which are regulated by cascade of sex steroid hormones. Pathological regulation of uterine extracellular matrix reported in diabetic patients. To know the extracellular modulation is essential to understanding implantation, feto-placental development and overcome the paths involved in female reproduction. Though ECM composed with very various components and it is complex, the present review focused on the fate of collagens during periimplantation period.

• The Journal of Korean Medicine
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• v.27 no.4
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• pp.12-29
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• 2006

Background and Aims : Even though various strategies for cancer treatment have advanced with the remarkable development of genomic information and technology, it is far from giving relief to cancer patients. Recently there is accumulating evidence that the immune system is closely connected to anti-tumor defense mechanisms in a multistage process. This includes tumorigenesis, invasion, growth and metastasis. Cordyceps Militaris, a well-known oriental herbal medicine, is a parasitic fungus that has been used as an immune enhancing agent for a long period of time. However, little is known about the cancer-related immunomodulatory effects and anti-tumor activities. In the present study, we aimed to investigate the effects of Cordyceps Militaris extract (CME) on immune modulating and anti-tumor activity. Materials and Methods : To elucidate the effects of CME on macrophage and natural killer (NK) cell activity, we analyzed nitric oxide (NO) production, NK cytotoxicity and gene expression of cytokines related with macrophages and NK cell activity. Results and Conclusions : CME activated and promoted macrophage production of NO. It also enhanced gene expression of IL-1 and iNOS in RAW 264.7 cells. CME promoted cytotoxicity of NK cells against YAC-1 cells and enhanced NK cell related gene expression such as IL-1, IL-2, IL-12, iNOS, IFN-${\gamma}$ and　TNF-${\alpha}$ in mice splenocytes. It also Promoted protein expression of IL-10, IL-12, IFN-${\gamma}$ and TNF-${\alpha}$ in mice splenocytes and inhibited lung tumor metastasis induced by CT-26 cell line compared with the control group. From these results, it could be concluded that CME is an effective herbal drug for modulating the immune system and anti-cancer treatment by promoting macrophage and NK cell activity.

• Journal of Food Hygiene and Safety
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• v.31 no.2
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• pp.67-73
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• 2016

Resveratrol is a non-flavonoid polyphenol which belongs to the stilbenes group and is naturally generated in several plants in response to damage or fungal invasion. It has been shown in published studies that resveratrol has an anti-adipogenic effect. A good consensus regarding the involvement of a down-regulation of $C/EBP{\alpha}$ and $PPAR{\gamma}$ in this effect has been reached. In addition, different metabolic pathways involved in triacylglycerol metabolism in white adipose tissue have been shown to be regulated by resveratrol. Concerning lipolysis, though this compound in itself seems to be unable to cause lipolysis, it increases lipid mobilization stimulated by ${\beta}-adrenergic$ agents. The increase in brown adipose tissue thermogenesis, and accordingly the associated energy dissipation, can attribute to accounting for the body-fat reducing effect of resveratrol. Besides its effects on adipose tissue, resveratrol can also acts on other organs and tissues. Therefore, it increases mitochondrial biogenesis and accordingly fatty acid oxidation in skeletal muscle and liver. This effect can also attribute to the body-fat reducing effect of this molecule. The present review purposes to collect the evidence concerning the potential mechanisms of action which underlie the anti-obesity effects of resveratrol, acquired either in cultured cells lines and animal models.

• Journal of Gastric Cancer
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• v.3 no.1
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• pp.38-43
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• 2003

Purpose: Caspase 2, a member of the family of ICE-like proteases, is activated by the Fas pathway and induces apoptosis by triggering the caspase cascade. The purpose of this study was to determine whether the expression pattern of caspase 2 might be associated with gastric cancer development and if so, to determine to which pathologic parameter it is linked. Materials and Methods: For the construction of the gastric cancer tissue microarray, 78 paraffin-embedded tissues containing gastric cancer areas were cored 3 times and transferred to the recipient master block. The expression pattern of caspase 2 was examined on tissue microarray slides by using immunohistochemistry and was compared with pathologic parameters, including histologic type, depth of invasion, lymph node metastasis, and peritoneal dissemination. Results: Caspase 2 was expressed on superficial and foveolar epithelial cells and lymphocytes in the gastric mucosa, mainly in cytoplasm. We found loss of caspase 2 expression in 41 ($52.6\%$) of the 78 gastric cancer tissues. Statistically, histologic type and other pathologic parameters were not related with loss of caspase 2 expression Conclusion: Our findings provide enough evidence that loss of caspase 2 expression may contribute to the development of Korean gastric cancer and that it might be one of the possible escape mechanisms from apoptosis in gastric cancer.

• Journal of Life Science
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• v.28 no.1
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• pp.116-129
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• 2018

Living creatures possess long-conserved mechanisms to maintain homeostasis in response to various stresses. However, chronic and continuous exposure to stress can result in the excessive production of stress hormones, including catecholamines, which have harmful effects on health. Studies on the relationship between the sympathetic nervous system (SNS) and cancer have been conducted based on the traditional hypothesis that stress can promote cancer progression. Many preclinical and epidemiological studies have suggested that the regulation of ${\beta}$-adrenergic signaling, which mediates SNS activity, can suppress the progression of solid tumors. SNS activation has highly pleiotropic effects on tumor biology, as it stimulates oncogenes, survival pathways, the epithelial - mesenchymal transition, and invasion. Moreover, it inhibits DNA repair and programmed cell death and regulates the tumor microenvironment, including immune cells, endothelial cells, the extracellular matrix, mesenchymal cells, and adipocytes. Although targeted therapies on the molecular basis of tumor proliferation are currently receiving increased attention, they have clinical limitations, such as the compensatory activation of other signaling pathways, emergence of drug resistance, and various side effects, which raise the need for pleiotropic cancer regulation. This review summarizes the effects of the SNS on the development and progression of cancer and discusses the clinical perspectives of ${\beta}$-blockade as a novel therapeutic strategy for this disease.