• Asian Pacific Journal of Cancer Prevention
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• 제15권16호
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• pp.6505-6510
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• 2014

Objective: This study was conducted to identify whether polymorphic variants of set domain-containing protein 8 (SET8) and tumor protein p53 (TP53) codon 72, either independently or jointly, might be associated with increased risk for cervical cancer. Methods: We genotyped SET8 and TP53 codon 72 polymorphisms of peripheral blood DNA from 114 cervical cancer patients and 200 controls using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and direct DNA sequencing. Results: The frequency of SET8 CC (odds ratios (OR) = 2.717, 95% CI=1.436-5.141) or TP53 GG (OR=2.168, 95% CI=1.149-4.089) genotype was associated with an increased risk of cervical cancer on comparison with the SET8 TT or TP53 CC genotypes, respectively. In additional, interaction between the SET8 and TP53 polymorphisms increased the risk of cervical cancer in a synergistic manner, with the OR being 9.913 (95% CI=2.028-48.459) for subjects carrying both SET8 CC and TP53 GG genotypes. Conclusion: These data suggest that there are significant associations between the miR-502-binding site SNP in the 3'-UTR of SET8 and the TP53 codon 72 polymorphism with cervical cancer in Chinese, and there is a gene-gene interaction.

• Asian Pacific Journal of Cancer Prevention
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• 제14권12호
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• pp.7501-7508
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• 2013

Background: Chronic myeloid leukemia (CML) is a myeloproliferative disorder of hematopoietic stem cell scarrying the Philadelphia (Ph) chromosome and an oncogenic BCR-ABL1 fusion gene. The tyrosine kinase inhibitor (TKI) of BCR-ABL1 kinase is a treatment of choice for control of CML. Objective: Recent studies have demonstrated that miRNAs within exosomes from cancer cells play crucial roles in initiation and progression. This study was performed to assess miRNAs within exosomes of K562 cells. Methods: miRNA microarray analysis of K562 cells and K562 cell-derived exosomes was conducted with the 6th generation miRCURYTM LNA Array (v.16.0). Gene ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were also carried out. GO terms and signaling pathways were categorized into 66 classes (including homophilic cell adhesion, negative regulation of apoptotic process, cell adhesion) and 26 signaling pathways (such as Wnt). Results: In exosomes, 49 miRNAs were up regulated as compared to K562 cells, and two of them were further confirmed by quantitative real-time PCR. There are differentially expressed miRNAs between K562 cell derived-exosomes and K562 cells. Conclusion: Selectively expressed miRNAs in exosomes may promote the development of CML via effects on interactions (e.g. adhesion) of CML cells with their microenvironment.

• 대한두경부종양학회지
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• 제20권2호
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• pp.147-155
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• 2004

Objectives: Head and neck squamous cell carcinoma (HNSCC) is the most common head and neck malignant tumor. The molecular genetic changes involving both oncogenes and tumor suppressor genes are known to be involved in head and neck squamous cell carcinogenesis, but the roles of the known tumor suppressor genes in carcinogenesis are not fully elucidated. The objectives of this study are to demonstrate the genetic alterations including the loss of heterozygosity (LOH) , amplification, and microsatellite instability of known tumor suppressor genes in HNSCC and to evaluate the relationship between genetic alterations of tumor suppressor genes and clinicopathologic features. Materials and Methods: Genetic alterations of 10 micro satellite markers of the 6 known tumor suppressor genes (APC, EXT1, DPC4, p16, FHIT, and PTEN) were analysed by DNA-PCR in paraffin-embedded histologically confirmed HNSCC specimens. Results: The genetic alterations of tumor suppressor genes were found frequently. Among the genetic alterations, LOH was most frequently found one. LOH was found frequently in APC (45.4%), EXT1 (36.4%), DPC4 (54.5%), and p16 (50%), but not found in FHIT. Also, the author found that abnormalities of APC gene was related to cervical lymph node metastasis and recurrence and that abnormalities of EXT1 gene were coexisted with those of APC gene or DPC4 gene. But these coexistences had no correlation with clinical features. Conclusion: These results suggested that APC, EXT1, p16, and DPC4 genes might play important roles and multiple tumor suppressor genes may participate dependently or independently in the carcinogenesis of HNSCC. These results also suggested that APC gene might relate to prognosis.

• Journal of Periodontal and Implant Science
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• 제45권4호
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• pp.145-151
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• 2015

Purpose: The aim of this study was to investigate the therapeutic effects of a herbal formula, PerioH-035, containing Angelica sinensis, steamed Rehmannia glutinosa, Angelica dahurica, Cimicifuga heracleifolia, and Zanthoxylum piperitum on the periodontal breakdown in a well-established ligature-induced periodontitis model in rats. Methods: Sprague-Dawley rats were randomly assigned to 1 of 4 groups: NL (non-ligatured), L (ligatured), P1 (ligatured and treated with 1 mg/mL PerioH-035), P100 (ligatured and treated with 100 mg/mL PerioH-035). Periodontitis was induced by placing a ligature around the mandibular first molars. PerioH-035 was topically applied to both sides of the first molar for 2 weeks. The right side of the mandibles was retrieved for micro-computed tomography (CT) and methylene blue staining to analyze alveolar bone loss. The left side of the mandibles was histologically analyzed by TRAP and H&E staining. The MMP-9 mRNA level in gingival tissue was investigated by RT-PCR. Results: Alveolar bone resorption was significantly reduced in the PerioH-035-treated groups. The number of dense multi-nucleated cells found to be TRAP-positive by staining in the ligatured rats was markedly decreased by PerioH-035 application. In addition, periodontal tissue destruction, especially cementum demineralization, was ameliorated in the P1 and P100 groups. Moreover, gingival tissue from the PerioH-035-treated group showed a decrease in the MMP-9 mRNA level, resulting in recovery of collagen degradation. Conclusions: These results suggest that PerioH-035 has therapeutic effects on periodontitis, and thus, PerioH-035 shows promise as a treatment for periodontitis.

• Asian Pacific Journal of Cancer Prevention
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• 제16권13호
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• pp.5471-5476
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• 2015

2-deoxy-D-Glucose (2DG) causes cytotoxicity in cancer cells by disrupting thiol metabolism. It is an effective component in therapeutic strategies. It targets the metabolism of cancer cells with glycolysis inhibitory activity. On the other hand, MLN4924, a newly discovered investigational small molecule inhibitor of NAE (NEDD8 activating enzyme), inactivates SCF E3 ligase and causes accumulation of its substrates which triggers apoptosis. Combination of these components might provide a more efficient approach to treatment. In this research, 2DG and MLN4924 were co-applied to breast cancer cells (MCF-7 and SKBR-3) and cytotoxic and apoptotic activity were evaluated the by Micro culture tetrazolium test (MTT), TUNEL and ELISA methods. Caspase3 and Bcl2 genes expression were evaluated by real time Q-PCR methods. The results showed that MLN4924 and MLN4924/2DG dose-dependently suppressed the proliferation of MCF7 and SKBR-3 cells. Cell survival of breast cancer cells exposed to the combination of 2DG/MLN4924 was decreased significantly compared to controls (p<0.05), while 2DG and MLN4924 alone had less pronounced effects on the cells. The obtained results suggest that 2DG/MLN4924 is much more efficient in breast cancer cell lines with enhanced cytotoxicity via inducing a apoptosis cell signaling gene, caspase-3.

• Asian Pacific Journal of Cancer Prevention
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• 제17권4호
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• pp.1887-1890
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• 2016

Breast cancer is the most common cause of cancer-related death among women in the whole world. MiR- 34a and let-7a are well known tumor suppressors that participate in the regulation of apoptosis, invasion and other cellular functions. In this study, expression of miR-34a, let-7a and apoptosis pathway genes such as Bcl-2, Caspase-3 and P53 were evaluated using quantitative real-time PCR in 45 paired samples of normal margin and tumor tissue collected from breast cancer patient at advanced stage (3-4). MiR-34a, let-7a, caspase-3 and P53 expression are reduced and Bcl-2 expression is increased within tumoral tissues in comparison with normal margin tissues. P53 expression directly or indirectly was correlated with miR-34a, let-7a, Bcl-2 and caspase-3 expression. In This study we found that MiR-34a and let-7a expression are reduced in the tumoral tissues. Down-regulation of these two molecules correlated with expression of genes associated with apoptosis. These results suggest that due to the correlation of miR-34a and let-7a with apoptotic and anti-apoptotic pathways these molecules could participate as regulators in advanced clinical stages of breast cancer and should be considered as markers for diagnosis, prognostic assessment and targeted therapy.

• Asian Pacific Journal of Cancer Prevention
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• 제14권9호
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• pp.5533-5537
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• 2013

MicroRNA-10b (miR-10b) has been reported to play an important role in some types of cancer, but the effects and possible mechanisms of action of miR-10b in the metastasis of nasopharyngeal carcinoma cells (NPC) have not been explored. The aim of the present study was to investigate the function of miR-10b in nasopharyngeal carcinoma and to determine the molecular mechanisms underlying its action. The MTT assay was used to assess proliferation of CNE-2Z cells. Wound healing and transwell migration assays were applied to assess cell migration and invasion, while and expression of E-cadherin and MMP-9 were detected using Western blot analysis. Real-time PCR was employed to detect the expression of genes related to migration and invasion and the $2^{-{\Delta}{\Delta}Ct}$ method was used to calculate the degree of expression. MTT assay showed the expression of miR-10b to have no effect on the proliferation of NPC cell lines. The wound healing assay showed that miR-10b mimics promoted the mobility and invasion of NPC cell lines. Inhibitors of miR-10b reduced the ability of NPC cell lines to migrate and invade. In addition, the expression of genes related to migration and invasion, such as E-cadherin, vimentin, and MMP-9, were confirmed to be different in the CNE-2Z NPC cell line transfected with miR-10b mimics and with miR-10b inhibitors. In the present study, miR-10b was found to upregulate the expression of MMP-9 and knockdown of miR-10b was found to significantly downregulate the expression of E-cadherin. On the whole, these results showed that miR-10b plays an important role in the invasion and metastasis of NPC cells.

• 한국재료학회:학술대회논문집
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• 한국재료학회 2010년도 춘계학술발표대회
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• pp.43.1-43.1
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• 2010

조직공학의 중요한 요소로 작용하는 scaffold는 여러 가지 필수적인 조건들을 만족시켜야 한다. 대표적인 특징들로는 (1)생분해성 및 비독성, (2)넓은 표면적을 갖는 상호 연결된 내부 다공성 구조, (3)구조적 안정성, (4)세포부착 기질의 제공, (5)낮은 면역 반응성, (6)혈전 형성 억제, (7)친수성, (8)생체 기능성 등을 들 수 있다. 이러한 scaffold가 갖추어야 할 특성 중에서 세포 부착 기질 제공을 위하여 scaffold에 표면 개질을 통한 기능기를 도입하였다. 본 연구에서는 BCP scaffold의 구조적 안정성 부여를 위하여 PCL(polycaprolactone)을 infiltration 하였다. PCL은 소수성의 특징을 갖고 있어 세포와 상호작용 할 수 있는 생물학적 반응기가 없기 때문에 세포와의 친화성이 떨어진다. 세포의 친화성을 높여주기 위해 실리콘의 전구체인 TEOS(tetraethly orthosilicate)를 코팅하고, 그 위에 카복실기(carboxylic acid group)를 도입하였다. 또한 세포의 고정화를 높여주기 위해 fibronectin을 코팅하여 BCP/PCL scaffold의 세포 친화성을 높여주었다. 이와 같이 제조된 고기능성 BCP/PCL scaffold의 내부 구조와 특성을 Micro-CT로 확인하였고, 또한 실리콘 코팅 여부를 확인하기 위하여 SEM-EDS를 통해 관찰하였으며, FT-IR 관찰을 통해 카복실기 도입 여부를 확인 하였다. 또한 생체적합성 평가를 위해 MTT assay, 조골세포의 부착에 미치는 영향을 관찰하기 위해 SEM, 조골세포의 유전자 발현에 미치는 영향을 관찰하기 위해 RT-PCR을 통해 확인 하였다.

• Biomolecules & Therapeutics
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• 제28권4호
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• pp.337-343
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• 2020

Activation of osteoclast and inactivation of osteoblast result in loss of bone mass with bone resorption, leading to the pathological progression of osteoporosis. The receptor activator of NF-κB ligand (RANKL) is a member of the TNF superfamily, and is a key mediator of osteoclast differentiation. A flavanone glycoside isolated from the fruit of Poncirus trifoliata, poncirin has anti-allergic, hypocholesterolemic, anti-inflammatory and anti-platelet activities. The present study investigates the effect of poncirin on osteoclast differentiation of RANKL-stimulated RAW264.7 cells. We observed reduced formation of RANKL-stimulated TRAP-positive multinucleated cells (a morphological feature of osteoclasts) after poncirin exposure. Real-time qPCR analysis showed suppression of the RANKL-mediated induction of key osteoclastogenic molecules such as NFATc1, TRAP, c-Fos, MMP9 and cathepsin K after poncirin treatment. Poncirin also inhibited the RANKL-mediated activation of NF-κB and, notably, JNK, without changes in ERK and p38 expression in RAW264.7 cells. Furthermore, we assessed the in vivo efficacy of poncirin in the lipopolysaccharide (LPS)-induced bone erosion model. Evaluating the micro-CT of femurs revealed that bone erosion in poncirin treated mice was markedly attenuated. Our results indicate that poncirin exerts anti-osteoclastic effects in vitro and in vivo by suppressing osteoclast differentiation. We believe that poncirin is a promising candidate for inflammatory bone loss therapeutics.

• Molecules and Cells
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• 제37권9호
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• pp.664-671
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• 2014

MiR-217 can function as an oncogene or a tumour suppressor gene depending on cell type. However, the function of miR-217 in lung cancer remains unclear to date. This study aims to evaluate the function of miR-217 in lung cancer and investigate its effect on the sensitivity of lung cancer cells to cisplatin. The expression of miR-217 was detected in 100 patients by real-time PCR. The effects of miR-217 overexpression on the proliferation, apoptosis, migration and invasion of SPC-A-1 and A549 cells were investigated. The target gene of miR-217 was predicted by Targetscan online software, screened by dual luciferase reporter gene assay and demonstrated by Western blot. Finally, the effects of miR-217 up-regulation on the sensitivity of A549 cells to cisplatin were determined. The expression of miR-217 was significantly lower in lung cancer tissues than in noncancerous tissues (p < 0.001). The overexpression of miR-217 significantly inhibited the proliferation, migration and invasion as well as promoted the apoptosis of lung cancer cells by targeting KRAS. The up-regulation of miR-217 enhanced the sensitivity of SPC-A-1 and A549 cells to cisplatin. In conclusion, miR-217 suppresses tumour development in lung cancer by targeting KRAS and enhances cell sensitivity to cisplatin. Our results encourage researchers to use cisplatin in combination with miR-217 to treat lung cancer. This regime might lead to low-dose cisplatin application and cisplatin side-effect reduction.