• Journal of dental hygiene science
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• v.10 no.5
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• pp.365-372
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• 2010

Caesalpinia sappan L. has long been commonly used in oriental folk medicines and as dyes materials. To investigate the antioxidative activities and antiproliferation effects of brazilin from C. sappan heart wood, the MeOH soluble extract was successively fractionated by using hexane, $CHCl_{3}$, EtOAc, BuOH, MeOH, and $H_{2}O$. In these fractions, we were purified brazilin from EtOAc fraction which partitioned to 3.94% of the highest yields. The effects of brazilin and the extracts on human oral carcinoma cells (KB) by MTT assay and their antioxidant activities by DPPH, TCA assay and Fenton reaction were tested. The results showed that the brazilin could inhibits the proliferation of KB cells and obviously decreased the production of nitric oxide of the cells. When the concentration of the brazilin reached to $100\;{\mu}g/ml$, the inhibition percentage of the cell growth was about 60%. In assay on antioxidant activities, The results showed that brazilin exhibit the highest capacity of DPPH free radical scavenging effects among tested extracts. When the concentration of brazilin reached to 1 mg/ml, the lipid peroxide inhibition and radical inhibition activities were determined to be 65.0% and 85.8%, respectively. These results are suggest that brazilin have stronger antiproliferation effect on KB cell and antioxidant properties.

• Journal of Life Science
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• v.19 no.8
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• pp.1047-1054
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• 2009

Oral squamous carcinoma (OSC) cells present resistance to chemotherapeutic agents-mediated apoptosis in the late stages of malignancy. Advances in the understanding of bacterial toxins have produced new strategies for the treatment of cancers. It was demonstrated here that Pseudomonas aeruginosa exotoxin A (PEA) significantly decreased the viability of chemoresistant YD-9 cells in the apoptosis mechanism. Apoptotic manifestations were evident through changes in nuclear morphology and generation of DNA fragmentation. PEA treatment induced caspase-3, -6 and -9 cleavage, and activation. These events preceded proteolysis of the caspase substrates poly (ADP-ribose) polymerase (PARP), DNA fragmentation factor 45 (DFF45), and lamin A in YD-9 cells. The reduction of mitochondrial membrane potential, release of cytochrome c and SmacjDlABLO from mitochondria to cytosol, andtranslocation of AlF into nucleus were shown. While p53, p21 and $14-3-3{\gamma}$ were upregulated, cyclin Band cdc2 were downregulated by PEA treatment. Taken together, PEA induces apoptosis in chemoresistant YD-9 cells via activation of caspases, mitochondrial events and regulation of cell cycle genes.

• Journal of Oral Medicine and Pain
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• v.36 no.3
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• pp.147-160
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• 2011

Eugenol (4-allyl-2-methoxyphenol) is a natural phenolic constituent extensively used in dentistry as a component of zinc oxide eugenol cement and is applied to the mouth environment. Chios gum mastic (CGM) is a resinous exudate obtained from the stem and the main leaves of Pistacia lenticulus tree native to Mediterranean areas. This study was undertaken to investigate the synergistic apoptotic effect of co-treatment with a natural product, CGM and natural phenolic compound, eugenol on SCC25 human tongue squamous cell carcinoma cell line. To investigate whether the co-treatment with eugenol and CGM compared to each single treatment efficiently reduces the viability of SCC25 cells, MTT assay was conducted. Induction and augmentation of apoptosis were confirmed by Hoechst staining, TUNEL staining and DNA hypoploidy. Westen blot analysis and immunofluorescent staining were performed to study the alterations of the expression level and the translocation of apoptosis-related proteins in co-treatment. In this study, co-treatment of with eugenol and CGM on SCC25 cells showed several lines of apoptotic manifestation such as nuclear condensations, DNA fragmentation, the increase and decrease of Bax and Bcl-2, decrease of DNA content, the release of cytochrome c into cytosol, translocation of AIF and DFF40 (CAD) onto nuclei, and activation of caspase-3, caspase-6 caspase-7, caspase-9, PARP, Lamin A/C and DFF45 (ICAD) whereas each single treated SCC25 cells did not show or very slightly these patterns. Although the single treatment of 40 ${\mu}g$/ml CGM and 0.5 mM eugenol for 24 h did not induce apoptosis, the co-treatment of these reagents prominently induced apoptosis. Therefore our data provide the possibility that combination therapy with CGM and eugenol could be considered as a novel therapeutic strategy for human oral squamous cell carcinoma.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.11
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• pp.5455-5461
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• 2012

Luteolin is a plant flavonoid which exhibits anti-oxidative, anti-inflammatory and anti-tumor effects. However, the antiproliferative potential of luteolin is not fully understood. In this study, we investigated the effect of luteolin on cell cycling and apoptosis in human esophageal squamous carcinoma cell line Eca109 cells. MTT assays showed that luteolin had obvious cytotoxicity on Eca109 with an $IC_{50}$ of $70.7{\pm}1.72{\mu}M$ at 24h. Luteolin arrested cell cycle progression in the G0/G1 phase and prevented entry into S phase in a dose- and time-dependent manner. as assessed by FCM. Luteolin induced apoptosis of Eca109 cells was demonstrated by AO/EB staining assay and annexin V-FITC/PI staining. Moreover, luteolin downregulated the expression of cyclin D1, survivin and c-myc, and it also upregulated the expression of p53, in line with the fact that luteolin was able to inhibit Eca109 cell proliferation.

• Molecular & Cellular Toxicology
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• v.2 no.4
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• pp.273-278
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• 2006

95 squamous cell lung carcinoma samples (normal tissue: 40 samples, tumor: 55 samples) were analyzed with 8 K cDNA microarray. 1-way ANOVA test was employed to select differentially expressed genes in tumor with FDR<0.01. Among the selected 1,655 genes, final 212 genes were chosen according to the expression fold change and used for following analysis. The expression of up-regulated 64 genes was verified with Reverse Transcription PCR and 10 genes were identified as candidates for SCC markers. In our opinion, those candidates can be exploited as diagnostic or therapeutic purposes. Gene Ontology (GO) based analysis was performed using those 212 genes, and following categories were revealed as significant biological processes: Immune response (GO: 0006955), antigen processing (GO: 0030333), inflammatory response (GO: 0006954), Cell adhesion (GO: 0007155), and Epidermis differentiation (GO: 0008544). Gene set enrichment analysis (GSEA) also carried out on overall gene expression profile with 522 functional gene sets. Glycolysis, cell cycle, K-ras and amino acid biosynthesis related gene sets were most distinguished. These results are consistent with the known characteristics of SCC and may be interconnected to rapid cell proliferation. However, the unexpected results from ERK activation in squamous cell carcinoma gripped our attention, and further studies are under progress.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.7
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• pp.2993-2999
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• 2014

Saccharina japonica is a family member of Phaeophyceae (brown macro-alga) and extensively cultivated in China, Japan and Korea. Here, the potential anti-cancer effect of n-hexane fraction of S. japonica was evaluated in SK-Hep1 human hepatocellular carcinoma cells. The N-hexane fraction reduced cell viability and increased the numbers of apoptotic cells in a both dose- and time-dependent manner. Apoptosis was activated by both caspase-dependent and independent pathways. The caspase-dependent cell death pathway is mediated by cell surface death receptors and activated caspase-8 amplified the apoptotic signal either through direct activation of downstream caspase-3 or pro-apoptotic proteins (Bad, Bax and Bak) subsequently leading to the release of cytochrome c. On the other hand, caspase-independent apoptosis appeared mediated by disruption of mitochondrial membrane potential and translocation of AIF to the nucleus where they induced chromatin condensation and/or large-scale DNA fragmentation. In addition, the n-hexane fraction induced endoplasmic reticulum (ER)-stress and cell cycle arrest. The results suggested that potential anti-cancer effects of n-hexane extract from S. japonica on SK-Hep1 cells.

• Journal of Physiology & Pathology in Korean Medicine
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• v.22 no.2
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• pp.377-384
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• 2008

The root of Vitis labrusca, is used as a source of health promoting drug in Korean traditional medicine. It has been reported that root of Vitis labrusca has antioxidant, anti lipid peroxidation and anti-reactive nitrogen species (RNS) activities. The aim of this study was to elucidate the molecular changes of apoptotic signaling pathways in phorbol 12-myristate 13 acetate (PMA)-induced human hepatocellular carcinoma cell line (Hep G2). The root of Vitis labrusca, ethanol extract (RVLEE) was tested for cell viability on Hep G2 cell using the MTT assay. RVLEE exhibited weak cytotoxic activity. However, treatment of Hep G2 cells with RVLEE suppressed PMA-induced cell proliferation. Also, dramatic changes of cell death signals in cellular molecules such as Chk2/Cds1, CIDE-B, CLIMP-63, Bax, Bcl-xL, C-myc, Bcl-2, Bric-5, NIP-3, TRAF2 and BAR but not CIDE-B and DR4. Futhermore, our results showed that the treatment of Hep G2 cells with 25 and $50\; {\mu}g/ml$ of RVLEE suppressed PMA-induced COX-2 gene activity. These data suggest that RVLEE have inhibitory effect of cell proliferation, induction of apoptosis and, thus, may offer therapeutic potential in Hep G2.

• Archives of Craniofacial Surgery
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• v.18 no.1
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• pp.37-43
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• 2017

Background: Skin cancer is the most common type of cancer. Of the 4 million skin lesions excised annually worldwide, approximately 2 million are considered cancerous. In this study, we aimed to describe a regional experience with skin cancers treated by a single senior surgeon and to provide a treatment algorithm. Methods: The medical records of 176 patients with head and neck non-melanocytic skin cancer (NMSC) who were treated by a single surgeon at our institution between January 2010 and May 2016 were retrospectively reviewed, and their data (age, sex, pathological type, tumor location/size, treatment modality) were analyzed. Patients with cutaneous squamous cell carcinoma (cSCC) who were classified as a high-risk group for nodal metastasis underwent sentinel node mapping according to the National Comprehensive Cancer Network guidelines. Results: Among the patients with NMSC who were treated during this period, basal cell carcinoma (BCC; n=102, 57.9%) was the most common pathological type, followed by cSCC (n=66, 37.5%). Most lesions were treated by complete excision, with tumor-free surgical margins determined via frozen section pathology. Thirty-one patients with high-metastasis-risk cSCC underwent sentinel node mapping, and 17 (54.8%) exhibited radiologically positive sentinel nodes. Although these nodes were pathologically negative for metastasis, 2 patients (6.5%) later developed lymph node metastases. Conclusion: In our experience, BCC treatment should comprise wide excision with tumor-free surgical margins and proper reconstruction. In contrast, patients with cSCC should undergo lymphoscintigraphy, as nodal metastases are a possibility. Proper diagnosis and treatment could reduce the undesirably high morbidity and mortality rates.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.4
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• pp.1463-1469
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• 2015

Background: To evaluate the safety and efficacy of combined chemoradiotherapy or radiotherapy alone in elderly patients with esophageal carcinoma to identify the best method of treatment. Materials and Methods: One hundred and sixteen patients with esophageal carcinoma aged 70 and older who received definitive radiotherapy or chemoradiotherapy entered the study. Overall survival (OS), disease-free survival (DFS) and treatment-related toxicities were assessed. Results: The median OS of the overall population was 17.9 months. For patients treated with cCRT, sCRT and radiotherapy alone, the median OS was 22.3 months, 18.0 months and 12.4 months respectively(P=0.044). Median OS for patients treated with radiotherapy dose ${\geq}60Gy$ and <60Gy was 20.2 months and 10.9 months respectively (p=0.017). By univariate analysis, Chemoradiotherapy (include cCRT and sCRT) and radiotherapy dose ${\geq}60Gy$ were found to achieve higher survival rates compared with radiotherapy alone and radiotherapy dose <60Gy (P=0.015, P=0.017). By multivariate analysis, chemoradiotherapy (HR=1.645, P=0.022) and radiotherapy dose ${\geq}60Gy$ (HR=1.642, P=0.025) were identified as independent prognostic factors of OS. Conclusions: Definitive concurrent chemoradiotherapy could be considered as a feasible and effective treatment in esophageal carcinoma patients aged 70 and older. Radiotherapy dose 60Gy is an effective treatment option compared with standard dose radiotherapy, while higher doses are not beneficial to improve survival.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.23
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• pp.10393-10396
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• 2015

Background: Endometral carcinoma is the most common malignant tumor of the female genital tract and the fourth most common cancer in women after breast, colorectal and lung cancers Hypoxia-inducible factor-1 (HIF-1) is a key transcription factor that regulates cellular response to hypoxia HIF-1 plays important roles in the development and progression of cancer through activation of various genes that are involved in crucial aspects of cancer biology, including angiogenesis, energy metabolism, vasomotor function, erythropoiesis, and cell survival. In this study, we aimed to investigate the association between HIF-1 1772 C/T polymorphisms and endometrial cancer. Materials and Methods: 75 patients with endometrial carcinoma and 75 patients whose underwent hysterectomy for non tumoral indication selected for evaluation of HIF-1 1772 C/T polymorphisms by PCR-RFLP and sequencing. Results: For the 1772 C/T polymorphism, the analysis showed that the T allele and genotype TT were significantly associated with endometrial cancer risk. Conclusions: Our results suggest that the C1772T polymorphism of the HIF-1a may be associated with endometrial cancers.