• Journal of Life Science
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• v.28 no.8
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• pp.992-998
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• 2018

Cancer cells grow in an environment composed of various components that supports tumor growth. Major cell types in the tumor microenvironment are fibroblast, endothelial cells and immune cells. All of these cells communicate with cancer cells. Among infiltrating immune cells as an abundant component of solid tumors, macrophages are a major component of the tumor microenvironment and orchestrates various aspects of immunity. The complex balance between pro-tumoral and anti-tumoral effects of immune cell infiltration can create a chronic inflammatory microenvironment essential for tumor growth and progression. Macrophages express different functional programs in response to microenvironmental signals, defined as M1 and M2 polarization. Tumor-associated macrophages (TAM) secret many cytokines, chemokines and proteases, which also promote tumor angiogenesis, growth, metastasis and immunosuppression. TAM have multifaceted roles in the development of many tumor types. TAM also interact with cancer stem cells. This interaction leads to tumorigenesis, metastasis, and drug resistance. TAM obtain various immunosuppressive functions to maintain the tumor microenvironment. TAM are characterized by their heterogeneity and plasticity, as they can be functionally reprogrammed to polarized phenotypes by exposure to cancer-related factors, stromal factors, infections, or even drug interventions. Because TAMs produce tumor-specific chemokines by the stimulation of stromal factors, chemokines might serve as biomarkers that reflect disease activity. The evidence has shown that cancer tissues with high infiltration of TAM are associated with poor patient prognosis and resistance to therapies. Targeting of TAM in tumors is considered a promising therapeutic strategy for anti-cancer treatment.

• Journal of Life Science
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• v.26 no.10
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• pp.1214-1217
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• 2016

Rebamipide is a mucosal-protective antiulcer drug, but its mechanism of action in gastric cancer remains elusive. CagA, a major virulence factor of Helicobacter pylori (H. pylori), is associated with the risk of gastric cancer. CagA protein is injected into gastric epithelial cells and deregulates a variety of cellular signaling molecules. CagA from H. pylori induces phospholipase D1 (PLD1) expression through NFκB activation in gastric epithelial cells, followed by invasion and proliferation of gastric epithelial cancer cells. Infection with cagA-positive H. pylori and expression of CagA enhances the binding of NFκB to the PLD1 promoter. Rebamipide abolishes H. pylori cagA-induced PLD1 expression via inhibition of binding of NFκB to the PLD1 promoter and also inhibits PLD activity. Moreover, rebamipide abolishes H. pylori CagA-induced β-catenin and the expression of a target cancer stem cell (CSC) marker gene via upregulation of miRNA-320a and -4496, followed by attenuation of self-renewal capacity of H. pylori CagA-infected gastric CSCs. In addition, rebamipide increases the chemosensitivity of CagA-expressed gastric CSCs and suppresses gastric carcinogenesis. Thus, it is speculated that rebamipide might show a potent efficacy as chemotherapeutic drug against gastric cancer cells. In this review, we summarizes recent results regarding the novel insights for the efficacy of rebamipide in gastric cancer cells.

• Polymer(Korea)
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• v.26 no.5
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• pp.691-700
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• 2002

Interstitial therapy using biodegradable polymeric device loaded with anticancer agent can deliver the drug to the tumor site at high concentration, resulting in an increase of therapeutic efficacy. 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU, carmustine) is most commonly used as chemotherapeutic agent for brain tumors. The design of implantable device is regarded as an important factor lot the efficient delivery of antitumor agent to targeting site. In order to control the release profile of drug, the release pattern of BCNU with the changes of various dimension and additives was investigated. The PLGA wafers containing 3.85, 10, 20 and 30% of BCNU were prepared in various shape (diameter of 3, 5 and 10 mm, thickness of 0.5, 1 and 2 mm) by direct compression method. In vitro drug release profile of BCNU-loaded PLGA wafers could be controlled by changing the dimension of wafers such as initial drug content, weight, diameter, thickness, volume and surface area of wafers, as well as PLGA molecular weight and additives. Drug release from BCNU-loaded PLGA wafers was facilitated with an increase of BCNU-loading amount or presence of poly(N-vinylpyrrolidone)(PVP) or sodium chloride (NaCl). The effects of various geometric factors and additives on the BCNU release pattern were confirmed by the investigation of mass loss and morphology of BCNU-loaded PLGA wafers.

• Journal of Biomedical Engineering Research
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• v.37 no.1
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• pp.46-52
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• 2016

Nanoparticles have been studied as therapeutic and imaging agents for the early detection and cure of cancer, Cancer Theranostics. Nanoparticles were considered to effectively target cancer cells due to Enhanced Permeability and Retention (EPR) effect and most nanoparticles have been evaluated by using spherical shapes. However, the problem that the EPR effect is not so effective for human cancer therapy was recently brought up. Therefore, in this study, we suggest novel discoidal nanoparticles to overcome this problem, focusing on their manufacturing process and quality control. Herein, we demonstrate the improved manufacturing method of discoidal nanoparticles and their potential to apply to MCF 7, human breast cancer treatment.

• Journal of Marine Bioscience and Biotechnology
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• v.1 no.4
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• pp.305-310
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• 2006

Abnormal activation of the Wnt/${\beta}$-catenin pathway and subsequent up-regulation of ${\beta}$-catenin response transcription (CRT) are associated with the development of colon cancer. Thus, the Wnt/${\beta}$-catenin pathway is an attractive target for chemoprevention and treatment of this cancer. In this study, we used a cell-based screen to identify a methanol extract of Dictyota dichotoma (EDD) that suppresses the Wnt/${\beta}$-catenin pathway without altering the level of ${\beta}$-catenin protein and reduces the expression of cyclin D1, which is a known ${\beta}$-catenin/T cell factor (TCF)-dependent gene. EDD inhibited the growth of various colon cancer cells. Our findings suggest that EDD can potentially be used as a chemopreventive agent against colon cancer.

• Journal of Life Science
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• v.24 no.10
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• pp.1137-1143
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• 2014

Doxorubicin is a general chemotherapy drug widely used for a number of cancers. However, the correlation between endogenous nitric oxide ($NO^{\bullet}$) levels and chemoresistance to doxorubicin remains unclear. In this study, we investigated the effect of endogenous $NO^{\bullet}$ on the anticancer activity of doxorubicin in human colon cancer cell lines HCT116 and HT29 with different p53 status. The cells were treated with either doxorubicin alone or in combination with the $NO^{\bullet}$ synthase (NOS) inhibitor $N^G$-monomethyl-L-arginine (NMA). Doxorubicin differentially inhibited the growth of both the HCT116 (p53-WT) and HT29 (p53-MUT) cells, which was mitigated by cotreatment with NMA. Further studies revealed that inhibition of endogenous $NO^{\bullet}$ mitigated doxorubicin-induced apoptosis in the HCT116 and HT29 cells, as evidenced by apoptotic DNA fragmentation and the sub-G1 peak of apoptotic markers. Apoptosis was delayed in the HT29 cells, and its magnitude was greatly reduced, underscoring the importance of the modulation of p53 in the response. RT-PCR analysis revealed that doxorubicin down-regulated levels of inhibitors of the apoptosis family (cellular IAP-1 and-2). Collectively, these data show that induction of apoptosis by doxorubicin in human colon cancer cells is possibly related to modulation of endogenous $NO^{\bullet}$, the expression of the IAP family of genes, and the status of p53. The underlying mechanisms may represent potential targets for adjuvant strategies to improve the efficacy of chemotherapy for colon cancer.

• Journal of the Korean Society of Food Science and Nutrition
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• v.41 no.12
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• pp.1701-1707
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• 2012

3,3'-Diindolylmethane (DIM) is a major in vivo derivative of the putative anticancer agent indole-3-carbinol, which is present in cruciferous vegetables and has been reported to have anti-carcinogenic properties. An abnorrmally elevated level of cyclooxygenase-2 (COX-2) has been implicated in the pathogenesis of carcinogenesis. To investigate the mechanism by which DIM exhibits anti-carcinogenic effects, we investigated the effects of DIM on COX-2 expression in MCF-10A human mammary epithelial cells treated with the tumor promoter 12-O-tetradecanoylphorbol 13-acetate (TPA). DIM inhibited TPA-induced COX-2 expression and suppressed the synthesis of prostaglandin $E_2$, one of the major products of COX-2. Nuclear factor-kappa B ($NF-{\kappa}B$) is a transcription factor known to play a role in regulation of COX-2 expression. Treatment of MCF-10A cells with TPA increased nuclear translocation of phospho-p65, with the maximal levels being reached at 1 hour, while DIM inhibited the TPA-induced nuclear translocation of phospho-p65. Overall, we demonstrated that DIM suppresses phorbol ester-induced $PGE_2$ production and COX-2 expression in MCF-10A cells. The reduction in COX-2 levels by DIM maybe mediated through inhibition of $NF-{\kappa}B$ signaling.

• Journal of Life Science
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• v.20 no.1
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• pp.103-112
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• 2010

Pemetrexed has demonstrated clinical activity in non-small cell lung cancer (NSCLC) as well as other solid tumors. It transports into the cells via reduced folate carrier (RFC) and is polyglutamated by folypolyglutamate synthetase (FPGS). Pemetrexed directly inhibits several folate-dependent enzymes such as thymidylate synthase (TS), dihydrofolate reductase (DHFR), and glycinamide ribonucleotide formyltransferase (GARFT). We investigated the effects of genetic variations and the expression of RFC, FPGS, TS and DHFR enzymes on drug sensitivity to pemetrexed in NSCLC cells. Polymorphisms in RFC, FPGS, and DHFR were genotyped in four NSCLC cells - A549, PC14, HCC-1588, and H226. Real-time RT-PCR and Western blot was performed to evaluate mRNA transcripts and protein of these genes. The cytotoxicity of pemetrexed was measured by SRB assay. In PC14 and H226 cells, increased mRNA expressions of RFC and FPGS were associated with higher cytotoxicity to pemetrexed. 2R/2R genotype of TS and its increased mRNA expression were associated with drug resistance to pemetrexed in A549 cells, whereas 3R/3R genotype in TS with decreased mRNA expression was associated with higher sensitivity in H226 cells. After pemetrexed treatment, an inverse change of DHFR mRNA and protein expression was found. The strongest linkage disequilibrium (LD) was discovered between-1726C>T and -1188A>C SNP of DHFR gene. Our findings suggest the cytotoxic effect of pemetrexed may be associated with genetic polymorphisms and the expression level of genes involved in pemetrexed metabolisms in NSCLC cells.

• Tuberculosis and Respiratory Diseases
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• v.62 no.2
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• pp.134-139
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• 2007

Gefitinib is a novel drug used to treat advanced non-small cell lung cancer. However, drug-related interstitial pneumonia is a major life-threatening side effect, which has a worldwide prevalence of 0.3-0.4%. In Japan, the prevalence is high as 3-4% but the actual frequency in Korea has not been officially assessed. We report two cases of gefitinib-induced interstitial lung disease during the treatment of non-small cell lung cancer. High-resolution computerized tomography (HRCT) of one case showed nonspecific ground glass opacity and the chest x-ray of another case showed diffuse bilateral ground glass opacity. The former patient showed a rapid good response to corticosteroid treatment whereas the latter died despite receiving aggressive treatment with high dose corticosteroid and empirical antibiotics.

• Journal of Life Science
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• v.33 no.11
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• pp.950-955
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• 2023

Cell division is an essential process for the survival and development of living organisms. It is critical that duplicated chromosomes are properly segregated into daughter cells during mitosis. The centrosome is the core organelle that forms the microtubule-organizing center (MTOC), which generates the microtubules that make up the mitotic spindle during cell division. The centrosome is also involved in cell signaling and motility. In normal cells, there is one centrosome in G1 that replicates into two in the S phase and matures through G2. During the M phase, duplicated centrosomes move to both ends of the cell, and spindle microtubules that are generated from MTOC move the chromosome to both ends. The cells then split into two to complete the cell division. However, a phenomenon called centrosome amplification (CA), in which the number of centrosomes is higher than normal, is common in cancer cells and can lead to chromosome instability (CIN). This paper discusses the process of centrosome replication and the role of PLK4 in this process. The possible consequences of centrosome amplification and how the PLK4 inhibitor may be able to treat certain types of cancer cells, such as breast cancer and neuroblastoma, will also be discussed.