• Biomedical Science Letters
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• v.20 no.2
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• pp.49-55
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• 2014

RalBP1 is an ATP-dependent non-ABC transporter, responsible for the major transport function in many cells including many cancer cell lines, causing efflux of glutathione-electrophile conjugates of both endogenous metabolites and environmental toxins. RalBP1 is expressed in most human tissues, and is over-expressed in non-small cell lung cancer cell lines and in many other tumor types. Blockade of RalBP1 by various approaches has been shown to increase sensitivity to radiation and chemotherapeutic drugs, leading to cell apoptosis. In xenograft tumor models in mice, RalBP1 blockade or depletion results in complete and sustained regression across many cancer cell types including lung cancer cells. In addition to its transport function, RalBP1 has many other cellular and physiological functions, based on its domain structure which includes a unique Ral-binding domain and a RhoGAP catalytic domain, as well as docking sites for multiple signaling proteins. Additionally, RalBP1 is also important for stromal cell function in tumors, as it was recently shown to be required for efficient endothelial cell function and angiogenesis in solid tumors. In this review, we discuss the cellular and physiological functions of RalBP1 in normal and lung cancer cells.

• Proceedings of the Korean Institute of Information and Commucation Sciences Conference
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• 2021.10a
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• pp.397-399
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• 2021

In this study, a basic study on the development of a multi-stimulation system was conducted to suppress lung cancer cell proliferation. Stimulation was applied to lung cancer cells using a photo-stimulating system and ultrasonic waves that generate a specific frequency, and the effect of inhibiting proliferation of cells was imaged and quantitatively evaluated. As a result of the experiment, when a single LED, single ultrasound stimulus were applied and ultrasound and LED stimuli were applied at the same time, meaningful results were shown in the proliferation rate of lung cancer cells.

• The Journal of Korean Medicine
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• v.23 no.1
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• pp.24-36
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• 2002

Objectives: The chemotherapeutic potential of Gagamgilgyung-tang for the treatment of human lung cancer, the antitumorigenic effects of Gagamgilgyung-tang on the proliferation and apoptosis of human lung cancer cell line A427 were investigated using molecular biological approaches, Methods: To determine Gagamgilgyung-tang concentrations which do not evoke cytotoxic damage to the cell line, cell viability was examined by MTT assay. To prove Gagamgilgyung-tang's antitumorigenic potential to human lung cancer, [3H]thymidine incorporation assay, trypan blue exclusion and Cpp32 protease activity assays and quantitative RT-PCR analysis were examined. Results: While A427 cells treated with $0.1-2.0{\mu\textrm{g}}/ml$ of Gagamgilgyung-tang showed no recognizable effect, marked reductions of cell viability were detected at concentrations over $5.0{\;}\mu\textrm{g}/ml$. DNA replication of A427 cells was inhibited by Gagamgilgyung-tang in a dose-dependent manner and Gagamgilgyung-tang induced the G1 cell cycle arrest through inhibition of DNA replication. Gagamgilgyung-tang triggered apoptotic cell death of A427 and enhanced the apoptotic sensitivity of the cells that were injured by a DNA damage-inducing chemotherapeutic drug etoposide. Gagamgilgyung-tang induces expression of growth-inhibiting genes such as p53 and p21/Wafl whereas it inhibited expression of growth-promoting genes such as c-Myc and Cyclin D1. Expression of a representative apoptosis-inducing gene Bax was also found to be induced by Gagamgilgyung-tang while apoptosis-suppressing Bcl-2 expression was not changed. Conclusions: Gagamgilgyung-tang could suppress the abnormal growth of tumor cells by suppressing the survival of genetically altered cells via induction of apoptosis. This study suggests that Gagamgilgyung-tang might have an antitumorigenic potential to human lung cancer cells, which might be associated with its growth-inhibiting and apoptosis-inducing properties.

• The Journal of Internal Korean Medicine
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• v.27 no.2
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• pp.379-393
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• 2006

Objectives: We are aimed to identify anti-tumor effects of Curcuma aromatics on some kinds of cancer cells through molecular biologic methods. Materials & Methods: We used 4 kinds of cancer cell lines such as lung cancer cells(AS49), cervical cancer cells(HeLa), glioma cancer cells(A172) and prostate cancer cells(PC3). We treated the boiled extract of Curcuma aromatica $5{\mu}g,\;10{\mu}g$ to cultural media(ml) for 24 hours. We measured the cytotoxicitv on 4 kinds of cancer cells through tryphan blue exclusion test and the suppressive effect on viability of 4 kinds of cancer cells via MTT assay. We measured change of mitochondria membrane potential via flow cytometry. The quantitative RT-PCR was used to examine the effect on the revelation of Bcl-2 and Bax which are genes related to apoptosis. We examined the effect on the revelation of Bcl-2 Protein and Bar protein by western blot analysis. Results : In the experiment of tryphan blue exclusion test, the extract of Curcuma aromatica showed more significant killing effect on AS49, HeLa than the control group with density dependent manner, which was statistically significant. In the experiment of MTT assay the extract of Curcuma aromatica showed more suppressive effect on viability of A549, HeLa than the control group with density dependent manner, which was statistically significant. Curcuma aromatica induced apoptosis by decreasing the membrane potential of mitochondria in A549, HeLa. In the experiment of the revelation of genes related to apoptosis, the revelation of Bcl-2 decreased and the revelation of Bax increased in A549, HeLa treated with Curcuma aromatica with dose dependent manner. In the experiment of the revelation of protein related to apoptosis, the protein levels of Bcl-2 decreased and the protein levels of Bax increased in AS49, HeLa treated with Curcuma aromatica with dose dependent manner. Conclusions: From this study, we can infer that Curcuma aromatica has anti-tumor effect on lung cancer cells and uterine carcinoma cells but not on glioma cells and prostate cancer cells.

• Molecules and Cells
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• v.39 no.8
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• pp.625-630
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• 2016

The RNA-binding protein Rbfox3 is a well-known splicing regulator that is used as a marker for post-mitotic neurons in various vertebrate species. Although recent studies indicate a variable expression of Rbfox3 in non-neuronal tissues, including lung tissue, its cellular function in lung cancer remains largely unknown. Here, we report that the number of RBFOX3-positive cells in tumorous lung tissue is lower than that in normal lung tissue. As the transforming growth factor-${\beta}$ (TGF-${\beta}$) signaling pathway is important in cancer progression, we investigated its role in RBFOX3 expression in A549 lung adenocarcinoma cells. TGF-${\beta}1$ treatment inhibited RBFOX3 expression at the transcriptional level. Further, RBFOX3 depletion led to a change in the expression levels of a subset of proteins related to epithelial-mesenchymal transition (EMT), such as E-cadherin and Claudin-1, during TGF-${\beta}1$-induced EMT. In immunofluorescence microscopic analysis, mesenchymal morphology was more prominent in RBFOX3-depleted cells than in control cells. These findings show that TGF-${\beta}$-induced RBFOX3 inhibition plays an important role in EMT and propose a novel role for RBFOX3 in cancer progression.

• Nuclear Engineering and Technology
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• v.40 no.7
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• pp.539-550
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• 2008

Lung cancer is the most prevalent global cancer, ${\sim}90%$ of which is caused by cigarette smoking. The LNT hypothesis has been inappropriately applied to estimate lung cancer risk due to ionizing radiation. A threshold of ${\sim}1\;Gy$ for lung cancer has been observed in never smokers. Lung cancer risk among nuclear workers, radiologists and diagnostically exposed patients was typically reduced by ${\sim}40%$ following exposure to <100 mSv low LET radiation. The consistency and magnitude of reduced lung cancer in nuclear workers and occurrence of reduced lung cancer in exposed non-worker populations could not be explained by the HWE. Ecologic studies of indoor radon showed highly significant reductions in lung cancer risk. A similar reduction in lung cancer was seen in a recent well designed case-control study of indoor radon, indicating that exposure to radon at the EPA action level is associated with a decrease of ${\sim}60%$ in lung cancer. A cumulative whole-body dose of ${\sim}1\;Gy$ gamma rays is associated with a marked decrease in smoking-induced lung cancer in plutonium workers. Low dose, low LET radiation appears to increase apoptosis mediated removal of $\alpha$-particle and cigarette smoke transformed pulmonary cells before they can develop into lung cancer.

• The Journal of Internal Korean Medicine
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• v.28 no.2
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• pp.294-303
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• 2007

Objectives : We are aimed to identify anti-tumor effects of realgar on some kinds of cancer cells through molecular biologic methods. Materials & Methods : We used 5 kinds of cancer cell lines: lung cancer cells(A549). stomach cancer cells(KATO) and neuroglioma cells(SUN-1118. U-87MG, U-373MG). We injected the boiled extracts of realgar $50{\mu}g$. $100{\mu}g$ to cultural media( ml )for 24 hours. We measured the killing effects on 5 kinds of cancer cells through inverted and fluorescence microscope, the suppressive effects on viability of those cells via XTT assay and the effects on the revelation of Bax and Bcl-2 proteins related to apoptosis by western blotting. Results : In the changes of morphology, the extracts of realgar showed more significant killing effects on all cancer cells. especially KATO, SNU-1118, U-87MG, U-373MG, than the control group with dose dependence, which was statistically significant. In XTT assay, the extracts of realgar showed more suppressive effects on viability of all cancer cells, especially KATO and U-373MG, than the control group with dose dependence, which was statistically significant. In the revelation of proteins related to apoptosis, the extracts of realgar increased the level of Bax and decreased that of Bcl-2 in all cancer cells with dose dependence. Conclusions : We identified that realgar had more anti-tumor effects on stomach cancer and neuroglioma than on lung cancer in the experiments above. However, these basic experiments were performed in vitro. We hope the anti-tumor effects of realgar will be practically identified through more progressive research.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.22
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• pp.9557-9565
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• 2014

MiRNAs are endogenous, single stranded ~22-nucleotide non-coding RNAs (ncRNAs) which are transcribed by RNA polymerase II and mediate negative post-transcriptional gene regulation through binding to 3'untranslated regions (UTR), possibly open reading frames (ORFs) or 5'UTRs of target mRNAs. MiRNAs are involved in the normal physiology of eukaryotic cells, so dysregulation may be associated with diseases like cancer, and neurodegenerative, heart and other disorders. Among all cancers, lung cancer, with high incidence and mortality worldwide, is classified into two main groups: non-small cell lung cancer and small cell lung cancer. Recent promising studies suggest that gene expression profiles and miRNA signatures could be a useful step in a noninvasive, low-cost and repeatable screening process of lung cancer. Similarly, every stage of lung development during fetal life is associated with specific miRNAs. Since lung development and lung cancer phenomena share the same physiological, biological and molecular processes like cell proliferation, development and shared mRNA or expression regulation pathways, and according to data adopted from various studies, they may have partially shared miRNA signature. Thus, focusing on lung cancer in relation to lung development in miRNA studies might provide clues for lung cancer diagnosis and prognosis.

• BMB Reports
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• v.40 no.3
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• pp.439-443
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• 2007

Tumor growth and metastasis are dependent on angiogenesis, and endothelial cell invasion and migration are apparent means of regulating tumor progression. We report here that saxatilin, a snake venom-derived disintegrin, suppresses the angiogenesis-inducing properties of NCI-H460 human lung cancer cells. Culture supernatants of NCI-H460 cells are able to induce human umbilical vascular endothelial cell (HUVEC) invasion and tube formation. However, treatment of the cancer cells with saxatilin resulted in reduced angiogenic activity of the culture supernatant. This suppressed angiogenic property was found to be associated with the level of vascular endothelial growth factor (VEGF) in the culture supernatant. Further experimental evidence indicated that saxatilin inhibits VEGF production in NCI-H460 cells by affecting hypoxia induced factor-1$\alpha$ (HIF-1$\alpha$) expression via the Akt pathway.

• Tuberculosis and Respiratory Diseases
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• v.48 no.3
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• pp.324-330
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• 2000

Objective : Lung cancer arises after a series of morphological changes, which take several years to progress from normal epithelium to invasive cancer. Multiple molecular changes and growth factor production have been documented in lung cancers, both small cell and non-small cell types. Insulin-like growth factors(IGFs) are important mitogenic and anabolic peptides, both in vivo and in vitro, and are thought to be significant autocrine-paracrine factors involved in normal and malignant cell proliferation. In this study, the degree of expression of IGF-1 on the immunohistochemical staining in human non-small cell lung cancer(NSCLC) cells and small cell lung cancer (SCLC) cells were investigated. Methods : Immunohistochemical staining for IGF-1 was performed in 15 cases of small cell carcinoma, 15 cases of squamous cell carcinoma, 15 cases of adenocarcinoma, and 12 cases of bronchoalveolar carcinoma. Results : The expression of IGF-1 on the immunohistochemical staining significantly increased in NSCLC cells than in SCLC cells. Conclusion : These results suggest the expression of IGF-1 in human lung cancer cells. The immunohistochemical staining of IGF-1 in lung cancer cell lines may assist in the differentiation of NSCLC and SCLC.