• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.40 no.6
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• pp.291-296
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• 2014

Objectives: Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is a side effect of bisphophonate therapy that has been reported in recent years. Osteoclastic inactivity by bisphosphonate is the known cause of BRONJ. Bone morphogenetic protein-2 (BMP-2) plays an important role in the development of bone. Recombinant human BMP-2 (rhBMP-2) is potentially useful as an activation factor for bone repair. We hypothesized that rhBMP-2 would enhance the osteoclast-osteoblast interaction related to bone remodeling. Materials and Methods: Human fetal osteoblast cells (hFOB 1.19) were treated with $100{\mu}M$ alendronate, and 100 ng/mL rhBMP-2 was added. Cells were incubated for a further 48 hours, and cell viability was measured using an MTT assay. Expression of the three cytokines from osteoblasts, receptor activator of nuclear factor-${\kappa}B$ ligand (RANKL), osteoprotegerin (OPG), and macrophage colony-stimulating factor (M-CSF), were analyzed by real-time polymerase chain reaction and enzyme-linked immunosorbent assay. Results: Cell viability was decreased to $82.75%{\pm}1.00%$ by alendronate and then increased to $110.43%{\pm}1.35%$ after treatment with rhBMP-2 (P<0.05, respectively). OPG, RANKL, and M-CSF expression were all decreased by alendronate treatment. RANKL and M-CSF expression were increased, but OPG was not significantly affected by rhBMP-2. Conclusion: rhBMP2 does not affect OPG gene expression in hFOB, but it may increase RANKL and M-CSF gene expression.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.11
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• pp.6595-6599
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• 2013

Leptin and its receptor are involved in breast carcinogenesis as mitogenic factors. Therefore, they could be considered as targets for breast cancer therapy. Expression of the leptin receptor gene could be modulated by leptin secretion. Silibinin and curcumin are herbal compounds with anti-cancer activity against breast cancer. The aim of this study was to assess their potential to inhibit of expression of the leptin gene and its receptor and leptin secretion. Cytotoxic effects of the two agents on combination on T47D breast cancer cells was investigated by MTT assay test after 24h treatment. With different concentrations the levels of leptin, leptin receptor genes expression were measured by reverse-transcription real-time PCR. Amount of secreted leptin in the culture medium was determined by ELISA. Data were statistically analyzed by one-way ANOVA test. The silibinin and curcumin combination inhibited growth of T47D cells in a dose dependent manner. There were also significant difference between control and treated cells in leptin expression and the quantity of secreted leptin with a relative decrease in leptin receptor expression. In conclusion, these herbal compounds inhibit the expression and secretion of leptin and it could probably be used as drug candidates for breast cancer therapy through leptin targeting in the future.

• Journal of Physiology & Pathology in Korean Medicine
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• v.18 no.2
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• pp.468-473
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• 2004

Psoriasis is a chronic inflammatory disease of the skin characterized by epidermal hyperplasia, dermal angiogenesis, infiltration of activated T cells, and increased cytokine levels, and affects 1-3% of the world-wide population. Although many immunological and clinical reports indicate a role for the immune system in the pathogenesis of psoriasis, puzzling questions about psoriasis remain unsolved. During the several decade, immunosuppressor and PUVA treatment are ubiquitously used to psoriasis therapy. But recently, to promote terminal differentiation of keratinocytes, block either NK-Tcell or T-cell activation, and interrupting the angiogenic switch represent another therapeutic opportunity in psoriasis. To keep face with immunological therapy, the needs of newly designed prescription on the psoriasis treatments were demanded. With the object of understand the psoriasis from an orient medical point of view, patients were administrated the GY during several weeks. We investigated the changes of gene expression in involved and uninvolved skin samples during the oriental remedy. Microarray data showed several important results. First, Gene expression profiling is similar to each patient. Second, precursor proteins that organize cornified envelops are decreased at the end of remedy. But genes which related to apoptosis, G-protein signalling, and lipid metabolism are increased. Third, 68.5% of clustering genes localized on the psoriasis susceptibility locus. In our results indicated that GY influence on the keratinocytes hyperproliferation by regulating the gene, which located on the psoriasis susceptibility locus.

• Journal of Breast Cancer
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• v.21 no.4
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• pp.343-353
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• 2018

Cancer is the leading cause of death worldwide. In developed as well as developing countries, breast cancer is the most common cancer found among women. Currently, treatment of breast cancer consists mainly of surgery, chemotherapy, hormone therapy, and radiotherapy. In recent years, because of increased understanding of the therapeutic potential of immunotherapy in cancer prevention, cancer vaccines have gained importance. Here, we review various immunotherapeutic breast cancer vaccines including peptide-based vaccines, whole tumor cell vaccines, gene-based vaccines, and dendritic cell vaccines. We also discuss novel nanotechnology-based approaches to improving breast cancer vaccine efficiency.

• Molecules and Cells
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• v.42 no.11
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• pp.804-809
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• 2019

Oncogenic gain-of-function mutations are clinical biomarkers for most targeted therapies, as well as represent direct targets for drug treatment. Although loss-of-function mutations involving the tumor suppressor gene, STK11 (LKB1) are important in lung cancer progression, STK11 is not the direct target for anticancer agents. We attempted to identify cancer transcriptome signatures associated with STK11 loss-of-function mutations. Several new sensitive and specific gene expression markers (ENO3, TTC39C, LGALS3, and MAML2) were identified using two orthogonal measures, i.e., fold change and odds ratio analyses of transcriptome data from cell lines and tissue samples. Among the markers identified, the ENO3 gene over-expression was found to be the direct consequence of STK11 loss-of-function. Furthermore, the knockdown of ENO3 expression exhibited selective anticancer effect in STK11 mutant cells compared with STK11 wild type (or recovered) cells. These findings suggest that ENO3-based targeted therapy might be promising for patients with lung cancer harboring STK11 mutations.

• Microbiology and Biotechnology Letters
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• v.48 no.4
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• pp.423-428
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• 2020

In vitro evolution is a powerful technique for the engineering of yeast strains to study cellular mechanisms associated with evolutionary adaptation; strains with desirable traits for industrial processes can also be generated. There are two distinct approaches to generate evolved strains in vitro: the sequential transfer of cells in the stationary phase into fresh medium or the continuous growth of cells in a chemostat bioreactor via the constant supply of fresh medium. In culture, evolutionary forces drive diverse adaptive mechanisms within the cell to overcome environmental or intracellular stressors. Especially, this engineering strategy has expanded to the field of human cell lines; the understanding of such adaptive mechanisms provides promising targets for the treatment of human genetic diseases and cancer. Therefore, this technology has the potential to generate numerous industrial, medical, and academic applications.

• Biomedical Science Letters
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• v.9 no.2
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• pp.67-74
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• 2003

Viral and non-viral vectors have been used in the delivery of genetic materials into animal cells and tissues, with each approach having pros and cons. Non-viral vectors have many useful merits such as easy preparation, low immunity and size tolerance of a transgene when compared to those of viral vectors. Delivery specificity may be achieved by complex formation between receptor ligands and a non-viral vector. In the present study, non-viral vector systems are investigated in an effort to find a practical delivery means for gene therapy, Receptor-ligand interaction between transferrin-receptor and transferrin was utilized for efficient gene transfer into cancer cells. A plasmid vector, pcDNA3 (LacZ) was ligated with a small duplexed oligo fragment in which a Biotin- VN$^{TM}$ phosphoramidite was placed in the middle of the oligo. The plasmid vector labeled by biotin was then conjugated with biotin-labeled transferrin via streptavidin. This trimeric conjugates were delivered to a hepatoma cell line, HepG2. The delivery efficiency of the trimeric conjugate was 2-fold higher than that of cationic liposomes used for transfection of a plasmid vector. These results demonstrate that a plasmid vector can be efficiently transferred into cells by forming a trimeric complex of plasmid vector-linker-ligand.

• KSBB Journal
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• v.32 no.3
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• pp.224-232
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• 2017

Resveratrol has been actively investigated as an anticancer drug since it induces cell growth inhibition and apoptosis in many cancer cells. Resveratrol acts through modulation of multiple pathways and genes. In this study, we found resveratrol reduced cell growth and mammosphere formation in MDA-MB-231 triple-negative human breast cancer cells. This suppressive effect of resveratrol is accompanied by a reduction in Bmi-1 gene expression. We also observed that knock-down of Bmi-1 gene by small interfering RNA effectively sensitizes breast cancer cells to resveratrol treatment. Our data demonstrate, for the first time, that resveratrol down-regulates Bmi-1 expression in human breast cancer cells and suggest that specific molecular targeting of Bmi-1 can be combined with a chemotherapeutic strategy to improve the response of breast cancer cells to resveratrol.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.1
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• pp.255-260
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• 2012

Patients with non-small cell lung cancer (NSCLC) who have activating epidermal growth factor receptor (EGFR) mutations derive clinical benefit from treatment with EGFR-tyrosine kinase inhibitors ((EGFR-TKIs)-namely gefitinib and erlotinib. However, these patients eventually develop resistance to EGFR-TKIs. Despite the fact that this acquired resistance may be the result of a secondary mutation in the EGFR gene, such as T790M or amplification of the MET proto-oncogene, there are other mechanisms which need to be explored. MicroRNAs (miRs) are a class of small non-coding RNAs that play pivotal roles in tumorigenesis, tumor progression and chemo-resistance. In this study, we firstly successfully established a gefitinib resistant cell line-HCC827/GR, by exposing normal HCC827 cells (an NSCLC cell line with a 746E-750A in-frame deletion of EGFR gene) to increasing concentrations of gefitinib. Then, we found that miR-214 was significantly up-regulated in HCC827/GR. We also showed that miR-214 and PTEN were inversely expressed in HCC827/GR. Knockdown of miR-214 altered the expression of PTEN and p-AKT and re-sensitized HCC827/GR to gefitinib. Taken together, miR-214 may regulate the acquired resistance to gefitinib in HCC827 via PTEN/AKT signaling pathway. Suppression of miR-214 may thus reverse the acquired resistance to EGFR-TKIs therapy.

• Tuberculosis and Respiratory Diseases
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• v.44 no.6
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• pp.1353-1365
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• 1997

Background : Tumor necrosis factor(TNF) has been considered as an important candidate for cancer gene therapy based on its potent anti-tumor activity. However, since the efficiency of current techniques of gene transfer is not satisfactory, the majority of current protocols is aiming the in vitro gene transfer to cancer cells and re-introducing genetically modified cancer cells to host. In the previous study, it was shown that TNF-sensitive cancer cells transfected with TNF-$\alpha$ cDNA would become highly resistant to TNF, and the probability was shown that the acquired resistance to TNF might be associated with synthesis of some protective protein. Understanding the mechanisms of TNF -resistance in TNF-$\alpha$ cDNA transfected cancer cells would be. an important step for improving the efficacy of cancer gene therapy as well as for better understandings of tumor biology. This study was designed to evaluate the role of MnSOD, an antioxidant enzyme, in the acquired resistance to TNF of TNF-$\alpha$ cDN A transfected cancer cells. Method : We transfected TNF-$\alpha$ c-DNA to WEHI164(murine fibrosarcoma cell line), NCI-H2058(human mesothelioma cell line), A549(human non-small cell lung cancer cell line), ME180(human cervix cancer cell line) cells using retroviral vector(pLT12SN(TNF)) and confirm the expression of TNF with PCR, ELISA, MIT assay. Then we determined the TNF resistance of TNF-$\alpha$ cDNA transfected cells(WEHI164-TNF, NCIH2058-TNF, A549-TNF, ME180-TNF) and the changes of MnSOD mRNA expressions with Northern blot analysis. Results : The MnSOD mRNA expressions of parental cells and genetically modified cells of WEHI164 and ME180 cells(both are naturally TNF sensitive) were not significantly different The MnSOD mRNA expressions of genetically modified cells of NCI-H2058 and A549(both are naturally TNF resistant) were higher than those of the parental cells, while those of parental cells with exogenous TNF were also elevated. Conclusion : The acquired resistance to TNF after TNF-$\alpha$ cDNA transfection may not be associated with the change in the MnSOD expression, but the difference in natural TNF sensitivity of each cell may be associated with the level of the MnSOD expression.