• Asian Pacific Journal of Cancer Prevention
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• v.17 no.2
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• pp.535-538
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• 2016

Background: Cyclooxygenase 2 (COX-2) is important as an enzyme in the pathway leading to the production of prostaglandin E2 (PGE2) and arachidonic acid. This pathway is known to play a role in inflammation, tumor growth, invasiveness and metastasis, inhibition of apoptosis and angiogenesis. Inhibition of COX-2 has been shown to be a promising antitumor and antiangiogenic strategy in several tumor types, including renal cell carcinoma (RCC). Therefore, we decided to evaluate the immunohistochemical expression of this marker and its association with several clinicopathological characteristics in a series of cases. Materials and Methods: COX-2 expression was examined immunohistochemically in tumor tissues obtained from 96 patients who underwent radical (94 cases) or partial (2 cases) nephrectomy. Correlations between COX-2 expression and clinicopathologic findings including pathologic stage, nuclear grade and other indicator of prognosis were examined. Results: Of 96 tumors, 20.9% were positive for COX-2 expression. A correlation was found between COX-2 expression and tumor histological subtype (P=0.03).The papillary subtype showed maximum expression of this marker (43.8%) and the clear subtype minimum (14.7%). There were also possible links between COX-2 expression and pathologic stage, nuclear grade and nodal involvement but the results were not statistically significant (P=0.8, P= 0.14 and P=0.06, respectively). No correlation was found between COX2 expression and patient age, gender, tumor size, metastasis or survival. Conclusions: In our study, COX-2 expression was correlated with the histological subtype of RCC. Additional research is required to determine the link between COX-2 expression and prognosis and also evaluation of probable effectiveness of COX-2 inhibitor drugs in treatment of RCC patients.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.33 no.2
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• pp.103-108
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• 2007

Cyclooxygenase-2 (Cox-2) is known as one of the critical factor in carcinomas of various organs. However, the importance of Cox-2 in oral squamous cell carcinoma has not been fully described yet. The purpose of this study is to evaluate the anti-cancer effect of selective cox-2 inhibitor, celecoxib in an oral squamous cell carcinoma cell line, KB with respect to cytotoxicity test, in vitro invasion and MMP-2 expression. In cytotoxicity test, celecoxib treated group showed definitely concentration dependent cytotoxicity. In addition, administration of celecoxib reduced the invasive potential of KB cell line significantly in invasion assay. However, there was no remarkable difference of the MMP-2 expression between the celecoxib treated group and the control group. Considering these data, celecoxib had a potential cytotoxic agent to oral squamous cell carcinoma cells. Also, it had anti-invasive property without acting on the MMP-2 expression mechanism. Therefore, it was postulated that celecoxib had the possibility of anti-cancer agent in treatment strategies of oral squamous cell carcinoma.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.28 no.6
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• pp.434-439
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• 2002

Oral squamous cell carcinoma (OSCC) is one of the most common head and neck cancers. OSCC generally has a poor prognosis due to its tendency towards a local invasion and subsequent metastasis, which is mediated by multiple proteolytic enzymes and angiogenesis. Soy products contain high levels of isoflavonoids, including the tyrosine kinase inhibitor, genistein, which has been identified as a potent inhibitor of cell proliferation and in vitro angiogenesis. The purpose of this in vitro study is to evaluate the anti-cancer effect of genistein with respect to the angiogenesis and basement membrane invasion in OSCC. The highly invasive OSCC cell line, HSC-3 cells were cultured in the presence of $10{\mu}M$ genistein for 24h. To evaluate the effects of genistein on the invasiveness and the gelatinolytic activity, in vitro invasion assay and zymography were performed. In order to evaluate the effect on the VEGF and bFGF mRNA expression, RT-PCR and northern hybridization reaction, and chemiluminescence detection were applied. The in vitro invasion assay showed that the genistein treatment reduced the cellular invasion through the artificial basement membrane and significant difference between the control group and the genistein treated group was shown in MMP-2 activity. Especially, the 62 kDa activated form of MMP-2 in the control group was 1.8 times higher than that in the genistein treated group. The results of the northern blot analyses indicated that VEGF mRNA expression in the genistein treated group was significantly down regulated. This study showed that genistein inhibits angiogenesis and reduces basement membrane invasion in OSCC. It seems to support the possibility of genistein as an anti-cancer agent.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.sup3
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• pp.81-85
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• 2016

Globally, the burden of breast cancer (BC) continues to increase. BC related lymphedema (BCRL) is currently non curable and as a life time risk it affects at least 25% of BC patients. Knowing more about BCRL and appropriate control of its modifiable risk factors can improve quality of life (QOL) of the affected patients. In this case control study to detect factors, 400 women with BCRL (as the case group) and 283 patients with BC without lymphedema (as the control group) that were referred to Shiraz University of Medical Sciences affiliated BC clinic center were assessed. The data were analyzed in SPSS. The mean age of the case group was $52.3{\pm}11.0years$ and of the control group was $50.1{\pm}10.9years$. In patients with BCRL, 203(50.7%) had left (Lt) side BC and in non- lymphedema group 151 (53.3%) had Lt side BC. Out of all BCRL patients, 204 (51%) had lymphedema in all parts of their affected upper extremities, 100 (25%) had swelling in the arm and forearm and 23 (5.7%) had edema in both the upper extremity and trunk. Edema, heaviness, concern about changing body image, pain and paresthesia were the most common signs/symptoms among patients with BCRL. In BCRL patients, the difference of circumference between the affected upper limb and non-affected limb was $4.4{\pm}2.5cm$ and the difference in volume displacement was $528.7{\pm}374.4milliliters$. Multiple variable analysis showed that moderate to severe activity (OR; odds ratio =14, 95% CI :2.6-73.3), invasiveness of BC (OR =13.7, 95% CI :7.3-25.6), modified radical mastectomy (OR=4.3, 95% CI :2.3-7.9), BMI =>25 (OR=4.2, 95% CI :2-8.7), radiotherapy (OR=3.9, 95% CI :1.8-8.2), past history of limb damage (OR=1.7, 95% CI :0.9-3.1) and the number of excised lymph nodes (OR=1.06, 95% CI :1.02-1.09) were the significant predictors of lymphedema in women with BC. Modifiable risk factors of BCRL such as non-guided moderate to severe physical activity, high BMI and trauma to the limb should be controlled as early as possible in BC patients to prevent development of BCRL and improve QOL of these patients.

• Journal of Physiology & Pathology in Korean Medicine
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• v.28 no.1
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• pp.22-28
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• 2014

Flos Sophorae, the dried flower bud of Sophora japonica L, possesses anti-inflammatory properties, prevents and treats blood capillary and hypertension diseases and can also be used as a hemostat. However, the effect of Flos Sophorae on breast cancer invasion is unknown. Matrix metalloproteinase-9 (MMP-9), which degrades the extracellular matrix, is a major component in cancer cell invasion. In this study, we investigated the inhibitory effect of Flos Sophorae extract (FSE) on 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced Matrix metalloproteinase-9 (MMP-9) expression and cell invasion, as well as the molecular mechanisms involved in Michigan Cancer Foundation-7 (MCF-7) cells. FSE inhibited the TPA-induced transcriptional activation of nuclear factor-kappa B (NF-${\kappa}B$). These results indicate that FSE-mediated inhibition of TPA-induced MMP-9 expression and cell invasion involves the suppression of NF-${\kappa}B$ pathway in MCF-7 cells. Thus, FSE may have therapeutic potential for controlling breast cancer invasiveness.

• Korean Journal of Otorhinolaryngology-Head and Neck Surgery
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• v.61 no.12
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• pp.697-701
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• 2018

Background and Objectives The aim of this study was to evaluate surgical completeness in endoscopic total thyroidectomy with central neck dissection via unilateral axillo-breast approach (UABA) compared with bilateral axillo-breast (BABA) and open approach (OA) by means of the radioactive iodine uptake (RAIU) ratio and thyroglobulin (Tg) of remnant thyroid. Subjects and Method From July 2010 to March 2013, 82 patients who had underwent total thyroidectomy with central neck dissection and postoperative radioactive iodine (RAI) ablation for papillary thyroid carcinoma were enrolled. Of these patients, 27 patients underwent UABA, 24 patients BABA, and 31 patients OA. Clinicopathologic data, surgical outcome, stimulated Tg and RAIU ratio on the first postoperative RAI ablation scan were compared among 3 groups. Results Patients in the endoscopic surgery groups (UABA, BABA) were younger than those in the OA groups. Invasiveness such as operation time, postoperative pain, and drain amount in UABA was less than that in BABA and severer than that in OA. Other variables regarding clinicopathologic and surgical data were not significantly different. Stimulated Tg and RAIU ratio did not show significant differences among 3 groups (p=0.659 and p=0.664). Conclusion The completeness of UABA was comparable with that of BABA and OA. The UABA may be a safe option for patients who need endoscopic thyroidectomy for papillary thyroid carcinoma.

• Journal of Life Science
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• v.19 no.9
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• pp.1200-1208
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• 2009

Tight junctions (TJs) that act as paracellular permeability barriers play an essential role in regulating the diffusion of fluid, electrolytes and macromolecules through the paracellular pathway. In this study, we investigated the correlation between the tightening of TJs, permeability and the invasive activity of genistein - a bioactive isoflavone of soybeans - in human breast carcinoma MCF-7 and MDA-MB-231 cells. The inhibitory effects of genistein on cell proliferation, motility and invasiveness were found to be associated with the increased tightness of the TJs, which was demonstrated by an increase in transepithelial electrical resistance and a decrease in paracellular permeability. Additionally, the immunoblotting results indicated that genistein repressed the levels of the proteins that comprise the major components of TJ, claudin-3 and claudin-4, which play a key role in the control and selectivity of paracellular transport. Furthermore, genistein decreased the metastasis-related gene expressions of insulin like growth factor-1 receptor and snail, while concurrently increasing that of thrombospondin-1 and E-cadherin. In addition, we demonstrated that claudins play an important role in the anti-motility and invasiveness of genistein using claudin-3 small interfering RNA. Taken together, our results indicate a possible role for genistein as an inhibitor of cancer cell invasion through the tightening of TJs, which may counteract the up-regulation of claudins. In addition, our results indicate that this may be beneficial for the inhibition of tumor metastasis.

• Molecules and Cells
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• v.43 no.7
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• pp.619-631
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• 2020

In this study, we describe a novel function of TNNC1 (Troponin C1, Slow Skeletal and Cardiac Type), a component of actin-bound troponin, as a tumor suppressor of lung adenocarcinoma (LUAD). First, the expression of TNNC1 was strongly down-regulated in cancer tissues compared to matched normal lung tissues, and down-regulation of TNNC1 was shown to be strongly correlated with increased mortality among LUAD patients. Interestingly, TNNC1 expression was enhanced by suppression of KRAS, and ectopic expression of TNNC1 in turn inhibited KRAS^G12D-mediated anchorage independent growth of NIH3T3 cells. Consistently, activation of KRAS pathway in LUAD patients was shown to be strongly correlated with down-regulation of TNNC1. In addition, ectopic expression of TNNC1 inhibited colony formation of multiple LUAD cell lines and induced DNA damage, cell cycle arrest and ultimately apoptosis. We further examined potential correlations between expression levels of TNNC1 and various clinical parameters and found that low-level expression is significantly associated with invasiveness of the tumor. Indeed, RNA interference-mediated down-regulation of TNNC1 led to significant enhancement of invasiveness in vitro. Collectively, our data indicate that TNNC1 has a novel function as a tumor suppressor and is targeted for down-regulation by KRAS pathway during the carcinogenesis of LUAD.

• Biomolecules & Therapeutics
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• v.25 no.2
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• pp.213-221
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• 2017

Baicalein, a natural flavonoid obtained from the rhizome of Scutellaria baicalensis Georgi, has been reported to have anticancer activities in several human cancer cell lines. However, its antimetastatic effects and associated mechanisms in melanoma cells have not been extensively studied. The current study examined the effects of baicalein on cell motility and anti-invasive activity using mouse melanoma B16F10 cells. Within the noncytotoxic concentration range, baicalein significantly inhibited the cell motility and invasiveness of B16F10 cells in a concentration-dependent manner. Baicalein also reduced the activity and expression of matrix metalloproteinase (MMP)-2 and -9; however, the levels of tissue inhibitor of metalloproteinase-1 and -2 were concomitantly increased. The inhibitory effects of baicalein on cell motility and invasiveness were found to be associated with its tightening of tight junction (TJ), which was demonstrated by an increase in transepithelial electrical resistance and downregulation of the claudin family of proteins. Additionally, treatment with baicalein markedly reduced the expression levels of lipopolysaccharide-induced phosphorylated Akt and the invasive activity in B16F10 cells. Taken together, these results suggest that baicalein inhibits B16F10 melanoma cell migration and invasion by reducing the expression of MMPs and tightening TJ through the suppression of claudin expression, possibly in association with a suppression of the phosphoinositide 3-kinase/Akt signaling pathway.

• Journal of Gastric Cancer
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• v.20 no.2
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• pp.212-224
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• 2020

Purpose: miR-205 is a tumor suppressor and plays an important role in tumor invasiveness. However, the role of miR-205 in human gastric cancer (GC) epithelial-mesenchymal transition (EMT) remains unclear. The aim of this study was to investigate the molecular mechanism of miR-205 in the regulation of EMT in GC invasion. Materials and Methods: Quantitative polymerase chain reaction (qPCR) was used to detect the expression of miR-205 in GC. Further, the correlation between the pathological parameters and prognosis of GC was statistically analyzed. A transwell model was used to evaluate the effect of miR-205-3p on the invasion and migration of GC cells. qPCR, western blotting, and luciferase assay were performed to analyze the relationship and target effects between miR-205-3p and the expression of zinc finger electron box binding homologous box 1 (ZEB1) and 2 (ZEB2). Results: We found that the levels of miR-205-3p were significantly lower (P<0.05) in GC tissues than in matched normal tissues. Additionally, the expression of miR-205-3p was related to the tumor invasion depth, lymph node metastasis, lymph node invasion, and tumor, node, metastasis stage. Patients with lower miR-205-3p expression levels in the tumors had a poorer prognosis. The in vitro assays indicated that miR-205-3p could affect the invasion ability and EMT of GC cells by targeting the expression of both ZEB1 and ZEB2. Conclusions: miR-205-3p promotes GC progression and affects the prognosis of patients by targeting both ZEB1 and ZEB2 to directly influence EMT.