Publications by authors named "Eung-Ryoung Lee"

Transmembrane Bax Inhibitor Motif-containing 6 (TMBIM6) has been reported to regulate cell death pathways and is overexpressed in several types of cancers. In this study, we investigated whether high expression of TMBIM6 in breast cancer was significantly associated with cancer invasiveness. Knockdown of reduced proliferation and migration of invasive breast cancer cells through downregulation of the MAPK/ERK signaling pathway.

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The non-small cell lung cancer (NSCLC) patients with EGFR-sensitive mutations can be therapeutically treated by EGFR-TKI such as erlotinib and gefitinib. However, about 40% of individuals harboring EGFR-TKI sensitive mutations are still resistant to EGFR-TKI. And, it has been reported that both PTEN loss and NF-κB activation contribute to intrinsic EGFR-TKI resistance in EGFR-mutant lung cancer.

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All cancers harbor molecular alterations in their genomes. The transcriptional consequences of these somatic mutations have not yet been comprehensively explored in lung cancer. Here we present the first large scale RNA sequencing study of lung adenocarcinoma, demonstrating its power to identify somatic point mutations as well as transcriptional variants such as gene fusions, alternative splicing events, and expression outliers.

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Bax inhibitor-1 (BI-1), a member of the BI-1 family of integral membrane proteins, was originally identified as an inhibitor of stress-induced cell death in mammalian cells. Previous studies have shown that the withdrawal of leukemia inhibitory factor (LIF) results in differentiation of the majority of mouse embryonic stem (mES) cells into various cell lineages, while some ES cells die within 3days. Thus, to investigate the function of BI-1 in ES cell survival and neuronal differentiation, we generated mES cell lines that overexpress BI-1 or a carboxy-terminal BI-1ΔC mutant.

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Imatinib mesylate, a Bcr/Abl tyrosine kinase inhibitor, is widely used in treating chronic myeloid leukemia. However, drug-resistance of leukemia cells becomes an emergent problem. Herein, various flavonoids were screened for applicability in leukemia treatment, and 3-hydroxyflavone (3-HF) was found to be most effective in reducing cancer cell viability.

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Article Synopsis
  • Embryonic stem (ES) cells are vital for regenerative medicine due to their ability to proliferate and differentiate into various cell types, but current maintenance techniques often lead to mixed cell populations.
  • Research shows that using nanopatterned polydimethylsiloxane (PDMS) as a culture substrate significantly enhances the self-renewal of mouse ES (mES) cells compared to traditional plastic dishes, preventing unwanted differentiation.
  • The study identifies that nanopattern PDMS boosts key signaling pathways like STAT3 and Akt, which are crucial for self-renewal, while also inhibiting processes that lead to differentiation, showcasing its potential in producing consistent, undifferentiated mES cells at scale.
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The nonobese diabetic (NOD) mouse is a classical animal model for autoimmune type 1 diabetes (T1D), closely mimicking features of human T1D. Thus, the NOD mouse presents an opportunity to test the effectiveness of induced pluripotent stem cells (iPSCs) as a therapeutic modality for T1D. Here, we demonstrate a proof of concept for cellular therapy using NOD mouse-derived iPSCs (NOD-iPSCs).

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Bax Inhibitor-1 (BI-1) is an evolutionally conserved apoptotic suppressor and belongs to the BI-1 family of proteins, which contain BI-1-like transmembrane domains. As their cellular functions and regulatory mechanisms remain incompletely understood, we compared their anti-apoptotic properties. Forced expression of BI-1 resulted in the most effective suppression of stress-induced apoptosis, compared with other family members, together with significant extracellular signal-regulated kinase (ERK)1/2 activation.

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Although flavonoids exhibit a variety of beneficial biological activities, the exact molecular mechanism of the cellular effects is still not fully explained. In this study, we investigated the molecular mechanism of cytoprotective effect of eriodictyol in UV-irradiated keratinocytes. We found that treatment with eriodictyol effectively suppressed the UV-induced cell death of the keratinocytes, concomitant with the inhibition of pro-caspase-3 or pro-caspase-9 cleavage and the suppression of cytochrome C release.

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Induced pluripotent stem (iPS) cells have been generated from various somatic cells; however, a major restriction of the technology is the use of potentially harmful genome-integrating viral DNAs. Here, without a viral vector, we generated iPS cells from fibroblasts using a non-viral magnetic nanoparticle-based transfection method that employs biodegradable cationic polymer PEI-coated super paramagnetic nanoparticles (NP). Our findings support the possible use of transient expression of iPS genes in somatic cells by magnet-based nanofection for efficient generation of iPS cells.

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Article Synopsis
  • NSAIDs like FR122047 show promise in cancer treatment by inducing apoptosis in breast cancer cells (MCF-7) through caspase activation.
  • The apoptosis caused by FR is primarily dependent on caspase-8, and inhibiting caspase-9 unexpectedly increases cell death, suggesting a complex relationship between these caspases.
  • Additionally, inhibiting caspase-9 disrupts autophagy, leading to increased cell death, while the effects of other drugs like sulforaphane differ, indicating varying mechanisms of action in cancer therapies.
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Non-steroidal anti-inflammatory drugs (NSAIDs), which inhibit the enzyme cyclooxygenase (COX), are known to have a potent anti-tumorigenic activity in various cancers. However, the responsible molecular mechanisms of COX inhibition in breast cancer cells remain to be completely elucidated. We examined the effect of the selective COX-1 inhibitor, FR122047 and the selective COX-2 inhibitor, SC791 on cell growth and apoptosis in human breast cancer MCF-7 cells which exhibited a high basal level of COX-1 expression.

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Recent studies reported that the direct transformation of one differentiated somatic cell type into another is possible. In the present study, we were able to modulate the cell fate of somatic cells to take on male germ cell function by introducing cell extracts derived from porcine testis tissue. Fibroblasts were treated with streptolysin O, which reversibly permeabilises the plasma membrane, and incubated with testis extracts.

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The molecular mechanisms underlying the kaempferol-induced cell death have not yet been fully explained. To investigate the role of kaempferol, widely distributed in foods, in tumor progression, human breast cancer cell line, MCF-7, was treated with kaempferol. Apoptosis was indicated by the accumulation of a sub-G1 population, as well as the appearance of 4'-6-diamidino-2-phenylindole (DAPI)-stained apoptotic nuclei in the MCF-7 cells after the administration of kaempferol.

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Here, we confirmed that stable expression of B-cell lymphoma-xL (Bcl-xL) in N18TG neuroglioma cells could suppress c-Jun N-terminal protein kinase (JNK) activation, nuclear fragmentation, and cell death caused by etoposide treatment. Moreover, additional overexpression of JNK1 led to partially antagonize the antiapoptotic environment attained by Bcl-xL, implying that JNK1-involved pathway may play a role in down-regulation of the antiapoptotic effect of Bcl-xL. However, the antagonistic effect of JNK1 on the antiapoptotic action of Bcl-xL was significantly weaker than that on the action of Bcl-2.

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In order to determine the effects of a variety of flavonoids, we applied differing amounts of several flavonoids to human breast cancer cells. Kaempferol treatment resulted in significant reduction of cell viability in the MCF-7 cells, although it exerted only minor effect on the cell viability of MDA-MB-231 or mammary epithelial HC-11 cells. Kaempferol was demonstrated to induce sustained ERK activation concomitantly with MEK1 and ELK1 activation, and this kaempferol-induced apoptosis was suppressed by treatment with PD98059, the overexpression of a kinase-inactive ERK mutant, or ERK siRNA.

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Although flavonoids, which are both qualitatively and quantitatively one of the largest groups of natural products, exhibit a variety of beneficial health effects, the exact molecular mechanism of the cellular activities is still not fully explained and there currently exists a lack of evidence for any relationship between the structure-activity relationship and apoptosis-inducing activity. In order to determine the importance of the OH group or substitution of the 5 or carbon-7 in the diphenylpropane skeleton of flavonoids, we originally synthesized several modified naringenin derivatives, including 7-O-benzyl naringenin (KUF-1) and 7-O-(MeO-L-Leu-D-Pro-carbonylmethyl) naringenin (KUF-7). Treatment with KUF-1 or KUF-7 resulted in significant apoptosis-inducing effects concomitant with chromatin condensation, caspase activation, and intracellular ROS production.

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Flavonoids are micronutrients that are widely detected in foods of plant origin and have been ascribed pharmacological properties. Several biological functions of flavonoids have been thus far identified, whereas there currently exists a lack of evidence to support the relationship between the structure-activity relationship and apoptosis-inducing activity. In an attempt to determine the importance of the OH group or substitution of the 5- or 7-carbon in the diphenylpropane skeleton of flavonoids, we selected 14 different flavonoids with different structures, particularly with regard to the 5- or 7-carbon, and found that naringenin treatment caused a slight decrease in the cell viability of the human colorectal carcinoma RKO cells.

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Recently, considerable scientific and therapeutic interest has focused on the structure and functions of the flavonoids. In a previous study, we suggested that hydroxyl (OH) substitutions on specific carbons in the skeleton of the flavonoids might significantly affect their apoptosis-modulating properties. Here, to investigate the effect of various OH substitutions on their diphenylpropane (C6C3C6) skeleton carbons, we selected 10 different flavonoids and assessed their role on UV-induced apoptosis of human keratinocytes, the principal cell type of epidermis.

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Flavonoids are highly diversified plant pigments that are present in a wide range of fruits, vegetables, nuts, and beverages. They are regularly consumed in the human diet and have various biological activities including anti-inflammatory, anti-cancer, and anti-viral properties. The flavonoids maybe one of the safest non-immunogenic drugs because they are small organic compounds which have been normally absorbed by the human body for long time.

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XaiF, a novel 32kDa protein encoded by the ORF located in the immediate downstream of the xynA gene of Bacillus stearothermophilus No. 236, was identified to be the xylanase-specific trans-activator. In this study, the positive effect of XaiF was confirmed to be xylanase-specific, and the results from Northern blot and in vitro transcription assays showed that the XaiF increased the xynA transcripts at post-transcriptional step.

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In order to elucidate the role of the mitogen-activated protein kinases, including JNK, p38 MAPK and ERK, as well as the survival-associated PI3K/Akt signaling pathway, in the response to chemotherapy, we have conducted a comparative study regarding the effects of doxorubicin on these pathways. Doxorubicin was determined to elicit the apoptosis of NIH3T3 cells in a dose-dependent manner. Prior to cell death, both Akt and p38 MAPK were transiently activated, and subsequently inactivated almost wholly, whereas ERK and JNK evidenced sustained activations in response to the drug treatment.

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The exact molecular mechanisms underlying the cellular effects associated with various flavonoids have yet to be fully explained. In the present study, we have administered several flavonoids to human HaCaT keratinocytes and determined that 3,4'-dihydroxy flavone (3,4'-DHF) exerts a slight stimulatory effect on cell growth, although other flavonoids, including kaempferol, quercetin, and isorhamnetin, exhibited growth inhibitory properties. 3,4'-DHF was found to exert an anti-apoptotic effect on etoposide-induced cell death of HaCaT keratinocytes.

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