• Journal of Life Science
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• v.26 no.6
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• pp.673-679
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• 2016

The development of safe and effective anti-cancer compounds has been seriously required to prevent and treat development of tumor in recent years. Among them, natural compounds derived traditional medicinal stuffs have been paid to attention as an anti-cancer candidate. In this study, aesculetin is a main component of a widely known as a medicinal stuff. It was reported that aesculetin has various biological effects such as anti-inflammatory and anti-bacterial, but its effect related to cell invasion was not discovered. Therefore, in this study, the effect of aesculetin on antioxidant and matrix metalloproteases (MMPs) was investigated in human fibrosarcoma cells, HT1080. First of all, aesculetin showed the scavenging activity of DPPH radical and reducing power in a dose dependent manner. As a result of cytotoxicity, the nontoxic concentration of aesculetin was below 2 μM in HT1080 cells performed by MTT assay. In addition, aesculetin displayed the inhibitory effect on MMP-9 activity related to cell invasion in experiment carried out by gelatin zymography assay. Furthermore, aesculetin increased the expression level of TIMP-1 but decreased the expression level of MMP-9 stimulated with PMA in western blot assay. Furthermore, aesculetin remarkably inhibited cell invasion related to metastasis a dose dependent manner. Above results suggest that aesculetin could exert chemopreventive effect through inhibition of activity and expression of MMP-9 related to cell invasion.

• Tuberculosis and Respiratory Diseases
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• v.48 no.6
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• pp.909-921
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• 2000

Background : Defects in apoptotic signaling pathways play important role in tumor initiation, progression, metastasis and resistance to treatment. Several proteins which may promote tumorigenesis by inhibiting apoptosis were identified. The survivin protein is the member of inhibitor of apoptosis protein(IAPs) family which inhibits apoptosis. Unlike other IAPs, it is expressed in during the fetal period but not in adult differentiated tissues. Many reports have stated that survivin is selectively expressed in many cancer cell lines and cancer tissues. We performed immunohistochemical analysis for survivin expression in non-mall cell lung cancer to get evaluate its clinical implication. Methods : Twenty nine surgically resected lung cancers were examined. Immunohistochemical staining were performed by immuno-peroxidase technique using avidin-biotinylated horseradish pemxidase complex in the formalin-fixed, paraffin-embedded tissue $4{\mu}m$ section. Anti-survivin polyclonal antibody was used for primary antibody and anti-p53 monoclonal antibody was also used to analyze the correlation between survivin and p53 expression. The survivin expression scores were determined by as the sum of the stained area and intensity. Results : Immunohistochemical analysis showed cancer specific expression of survivin in 20 of 29 cases (69.0%). Western blot analysis also showed the selective survivin expression in tumor tissue. There was no correlation between survivin expression and clinicopathological parameters and prognosis. We analyzed the ∞π'elation between survivin expression and p53 expression, but found none. Conclusion: We confirmed the tumor specific expression of survival in non-small cell lung canær. But this expression was not correlated with clinical parameters as well as histology, tumor stage, recurrence, and survival rate. Also it was not statistically correlated with the expression of p53.

• Korean Journal of Head & Neck Oncology
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• v.22 no.2
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• pp.123-129
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• 2006

Objective ： This retrospective study was designed to evaluate the anti-tumor efficacy and toxicities of the radiation therapy(RT) combined with cisplatin-based chemotherapy in locally advanced nasopharyngeal cancer(NPC). Materials and Methods ： Fifty three patients with locally advanced NPCs(AJCC stage II, III, IV) received curative RT and cisplatin-based chemotherapy. Duration of follow-up ranged from 5.5 to 201 months(median 50.8 months). Nineteen patients(35.8%) were treated with induction chemotherapy including cisplatin $100mg/m^2$ for 1 day and 5-fluorouracil $1g/m^2$ for 5 days followed by RT(Induction CTx-RT). Another 34 patients (64.2%) were treated with concurrent chemoradiation(CCRT) using cisplatin $100mg/m^2$(D1, 22, 43). Results ： Thirty-six(67.9%) and 11(20.8%) patients achieved clinical complete response and partial response, respectively. The pattern of failure was as follows：14 locoregional recurrence(26.4%) and 7 distant metastasis(13.2%). Among them, two patients(3.8%) had both locoregional and distant failure. Median overall survival(OS) and progression-free survival(PFS) were 85.5 months and 87.5 months, respectively. Five-year OS rate was 57.1%. The stage(AJCC), tumor response to chemoradiation and T stage were significant prognostic factors for OS(p=0.0113, p=0.0362 and p=0.0469). The stage(AJCC), tumor response to chemoradiation were also significant prognostic factors for PFS(p=0.0329, p=0.0424). Compared to each treatment group(Induction CTx-RT vs. CCRT), there were no significant differences in OS and PFS(p=0.7000, p=0.8261). Grade 3-4 mucositis, nausea/vomiting and hematological toxicities were noticed in 35.8%, 11.3% and 13.2%, respectively. Delayed RT over 2 weeks was inevitable in 26.5%. Seventeen patients(50%) successfully completed planned 3 courses of cisplatin in CCRT group. Conclusions ： RT combined with cisplatin-based chemotherapy in locally advanced NPC showed high response rate, good locoregional control, and survival rate. As expected, frequency of acute toxicities increased, and the patient's compliance to treatment was need to be improved. Although our data could not show additional survival benefit of CCRT compare to that of induction chemotherapy followed by RT, patients' accrual and further follow-up are required due to limitation of retrospective study.

• Journal of Korean Traditional Oncology
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• v.16 no.2
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• pp.35-41
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• 2011

Background : Lung cancer is one of the most common malignancy in the world. Types of lung cancer are Non small cell lung cancer and small cell lung cancer. Subtypes of Non small cell lung cancer are adenocarcinoma, squamous cell carcinoma and large cell carcinoma. Knowing the type of lung cancer is important in determining both treatment and prognosis. Recently, due to newly developed anti-cancer drugs, squamous cell carcinoma has relatively poor prognosis than non-squamous cell carcinoma. Case : We report a squamous cell lung cancer case treated with allergen removed Rhus verniciflua Stokes (aRVS) extract. The patients initially diagnosed stage squamous cell lung carcinoma, but she refused recommended operation. She initiated aRVS extract monotherapy in October. 2006. The follow up Computed tomography in March. 2007, she diagnosed stable disease of tumor response on aRVS treatment. However, this case was lost to follow up for 6 months while she was treated with tomotherapy. In October 2007, she came back to our cancer center after diagnosed stage IV metastasized lung to lung, and aRVS monotherapy was restarted. She had survived 2 years after metastasis of squamous cell lung carcinoma. Conclusion : Allergen removed Rhus verniciflua Stokes(aRVS) sucessfully prolonged overall survival of a squamous cell lung cancer patient.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.11
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• pp.5897-5901
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• 2012

The aim of the study was to clarify the role of gastrokine 1 in the process of formation and development of gastric cancer. The expression of gastrokine 1 in gastric cancer and corresponding non-cancerous gastric tissues of 52 gastric cancer patients was assessed with the real-time fluorescence quantitative polymerase chain reaction (RT-PCR) and immunohistochemistry. We also analyzed the relationship between the expression level and clinicopathological characteristics. Gastrokine 1 gene and protein expression in gastric cancer tissues was in both cases significantly lower than in corresponding non-cancerous gastric tissues (both P<0.01), but no significant relationship was found with clinicopathological parameters including tumor location, depth of invasion, differentiation, lymph node metastasis, stage, gender, age and carcinoembryonic antigen (CEA), and carbohydrate antigen 19-9 (CA19-9) level in peripheral blood preoperation of patients (P>0.05, respectively). Furthermore, gastrokine 1 gene expression was markedly lower in gastric cancer tissues of Helicobacter pylori (HP)-positive patients than negative ones (P<0.05). The result of the study showed that gastrokine 1 might play a significant role in the process of formation and development of gastric cancer as an anti-oncogene. Its effect might be weakened by HP infection.

• Journal of Life Science
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• v.20 no.12
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• pp.1784-1791
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• 2010

In this study, we investigated the effects of ethyl alcohol extracts of Hizikia fusiforme (EHF) on the correlation between tightening of tight junctions (TJs) and anti-invasive activity in human gastric adenocarcinoma AGS cells. Inhibitory effects of EHF on cell proliferation, motility, and invasiveness were found to be associated with increased tightness of the TJs, which was demonstrated by an increase in transepithelial electrical resistance. Activities of matrix metalloprotease (MMP)-2 and -9 in AGS cells were dose-dependently inhibited by treatment with EHF, and this was also correlated with a decrease in expression of their mRNA and proteins; however, tissue inhibitor of metalloproteinase (TIMP)-1 and -2 mRNA levels were increased. Additionally, immunoblotting results indicated that EHF repressed the levels of claudin proteins (claudin-1, -3, and -4), major components of TJs that play key roles in control and selectivity of paracellular transport. Furthermore, EHF decreased expression of insulin such as growth factor-1 receptor proteins, while concurrently increasing that of thrombospondin-1 and E-cadherin. In conclusion, these results suggest that EHF treatment may inhibit tumor cell motility and invasion, and therefore act as a dietary source to decrease the risk of cancer metastasis.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.15
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• pp.6335-6338
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• 2015

Background: Cancers have dysfunctional redox regulation resulting in production of reactive oxygen species (ROS), damaging DNA, RNA and free NTPs, and causing the accumulation of oxidative nucleic acids in cytoplasm. The major types are 8-oxo-7,8-dihydroguanine(8-oxoGsn) in RNA and 8-oxo-7,8-dihydro-2' deoxyguanosine(8-oxodGsn) in Mt-DNA. The MTH1 protein sanitizes oxidized nucleotide pools from NTPs to monophosphates, preventing the occurrence of transversion mutations. This study concerned cytoplasmic 8-oxodGsn/Gsn and MTH1 expression in gastric cancer and para-cancer tissues and elucidated roles of nucleic-acid oxidation and anti-oxidation. Materials and Methods: A polymer HRP detection system was used to detect 8-oxo-Gsn/dGsn and MTH1 expression in 51 gastric cancer and para-cancer tissue samples. Analyses of patient clinical and pathological data were also performed. Results: The expression of MTH1 and the 8-oxo-dGsn/Gsn ratio were significantly higher in cancer tissues than para-cancer tissues (P<0.05). Cytoplasmic 8-oxo-Gsn and MTH1 were both found to positively correlate (P<0.05) with tumor differentiation, while no significant associations were found with gender, age, invasion depth, lymph node metastasis and clinical stage (P>0.05). Conclusions: We found 8-oxo-dGsn/Gsn and MTH1 are both highly expressed in gastric cancer tissues, especially in well differentiated lesions. In addition, oxidated mtDNA is prevalently expressed in gastric cancers, while 8-oxo-Gsn expression in cytoplasmic RNA is a bit lower, but more selectively.

• Journal of Ginseng Research
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• v.40 no.2
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• pp.151-159
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• 2016

Background: Ginsenoside-Rg3, the pharmacologically active component of red ginseng, has been found to inhibit tumor growth, invasion, metastasis, and angiogenesis in various cancer models. Previously, we found that 20(R)-ginsenoside-Rg3 (Rg3) could inhibit angiogenesis. Since microRNAs (miRNAs) have been shown to affect many biological processes, they might play an important role in ginsenoside-mediated angiomodulation. Methods: In this study, we examined the underlying mechanisms of Rg3-induced angiosuppression through modulating the miRNA expression. In the miRNA-expression profiling analysis, six miRNAs and three miRNAs were found to be up- or down-regulated in vascular-endothelial-growth-factor-induced human-umbilical-vein endothelial cells (HUVECs) after Rg3 treatment, respectively. Results: A computational prediction suggested that mature hsa-miR-520h (miR-520h) targets ephrin receptor (Eph) B2 and EphB4, and hence, affecting angiogenesis. The up-regulation of miR-520h after Rg3 treatment was validated by quantitative real-time polymerase chain reaction, while the protein expressions of EphB2 and EphB4 were found to decrease, respectively. The mimics and inhibitors of miR- 520h were transfected into HUVECs and injected into zebra-fish embryos. The results showed that overexpression of miR-520h could significantly suppress the EphB2 and EphB4 protein expression, proliferation, and tubulogenesis of HUVECs, and the subintestinal-vessel formation of the zebra fish. Conclusion: These results might provide further information on the mechanism of Rg3-induced angiosuppression and the involvement of miRNAs in angiogenesis.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.12
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• pp.4863-4867
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• 2015

Background: Triple negative breast cancer (TNBC), characterized as estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 Her2 negative and accounting for 10-17% of all breast carcinomas, is only partially responsive to chemotherapy and suffers from a lack of clinically established targeted therapies. The aim of the current study was to evaluate the patterns of treatment and clinicopathology figures in Kurdish patients with triple-negative breast cancer, and to compare these to other reports. Materials and Methods: Between 2001 and 2014, 950 breast cancer patients were referred to our clinic. There were 74 female patients with TNBC, including 70 patients was invasive ductal carcinoma entered into our study. ER and PR positivity was defined as positive immunohistochemical staining in more than 10% of tumor cells. Immunohistochemistry assay with anti-HER2 antibodies was used to identify HER negative (0 and 1+) or positive (2+ and 3+). HER2 gene amplification was determined by fluorescent in situ hybridization (FISH). Overall survival (OS) was plotted with GraphPad Prism 5 Software using Kaplan-Meier and log-rank tests for comparison of results. Results: The mean age in the first diagnosis for 70 patients with triple TNBC and invasive ductal carcinoma was 49.6 years that range of age was 27-82 years. All of the patients were female. Of 70 patients, 23 patients had metastasis. Thirty-two patients (45.7%) were treated with tamoxifen and 39 (55.7%) with radiotherapy. Three-year, 5-year and 10-year OS rates for all patients were 82%, 72% and 64%, respectively. Conclusions: The OS in our West Iran TNBC patients is less than reported elsewhere. However, treatment with combination of tamoxifen plus radiation increases the OS and reduces the mortality rate.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.24
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• pp.10705-10711
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• 2015

Oral cancer is one of the most common and lethal cancers in the world. Combination chemotherapy coupled with nanoparticle drug delivery holds substantial promise in cancer therapy. This study aimed to evaluate the efficacy and safety of two dosages of our novel pH and temperature sensitive doxorubicin-methotrexate-loaded nanoparticles (DOX-MTX NPs) with attention to the MMP-2 mRNA profile in a 4-nitroquinoline-1-oxide induced oral squamous cell carcinoma (OSCC) model in the rat. Our results showed that both IV and oral dosages of DOX-MTX NP caused significant decrease in mRNA levels of MMP-2 compared to the untreated group (p<0.003). Surprisingly, MMP-2 mRNA was not affected in DOX treated compared to cancer group (p>0.05). Our results indicated that IV dosage of MTX-DOX is more effective than free DOX (12 fold) in inhibiting the activity of MMP-2 in OSCCs (P<0.001). Furthermore, MMP-2 mRNA expression in the DOX-MTX treated group showed a significant relation with histopathological changes (P=0.011). Compared to the untreated cancer group, we observed no pathological changes and neither a significant alteration in MMP-2 amount in either of healthy controls that were treated with oral and IV dosages of DOX-MTX NPs whilst cancer group showed a high level of MMP-2 expression compared to healthy controls (p<0.001).Taking together our results indicate that DOX-MTX NPs is a safe chemotherapeutic nanodrug that its oral and IV forms possess potent anti-cancer properties on aggressive tumors like OSCC, possibly by affecting the expression of genes that drive tumor invasion and metastasis.