• Korean Journal of Head & Neck Oncology
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• v.27 no.1
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• pp.17-21
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• 2011

연구 및 목적 : 이번 연구의 목적은 한국인에서 편도 편평세포암종의 발생에 고위험 인간유두종 바이러스(high risk human pap-illomavirus)의 역할 및 관여 인자에 대해 밝히고자 한다. 재료 및 방법 : 연구는 편도 편평상피세포암종으로 진단받은 54명을 대상으로 하였다. 고위험 인간유두종 바이러스의 감염을 알기위해 in situ hybridization 방법을 이용하였다. 고위험 인간유두종 바이러스의 감염과 나이, 성별, 흡연, 음주, 병기, 병리학적 특징 등과의 관계를 분석하였다. 결 과 : 고위험 인간유두종 바이러스의 양성율은 31.5%(17/54)였다. 고위험 인간유두종 바이러스 감염은 젊은 연령(50세 미만), 비흡연자, 림프절 전이와 유의한 상관관계가 있었다(각각 p=0.008, p=0.042, p=0.027). 하지만 성별, 음주, 원발부위 병기, 종양분화도, 피막외침범, 혈관 및 신경 침범과 고위험 인간유두종 바이러스와의 관계는 통계적으로 유의하지 않았다. 6개월 이상 추적 관찰이 가능한 환자를 대상으로 조사한 5년 전체 생존율 및 질병 특이 생존율은 각각 60%와 62%였다. 고위험 인간유두종 바이러스의 양성율은 질병 특이 생존율과 유의한 상관관계가 있었다(p=0.019). 결 론 : 한국인의 고위험 인간유두종 바이러스 감염은 젊은 연령 및 비흡연자의 편도 편평세포암종의 발생에 관련이 있고 예후 인자로 중요한 역할을 한다.

• Journal of Food Hygiene and Safety
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• v.26 no.4
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• pp.398-402
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• 2011

Cruciferous vegetables including diindolylmethane (DIM) have been shown to have anticancer activity. Especially, DIM-pPhBr and DIM-pPhF used in this study was reported to have more effective and less toxic effects than DIM. However, there is no report presenting their anti-tumorigenic activity in oral cancer. In the present study, we examined the effects of DIM-pPhBr and DIM-pPhF on the cell proliferation and apoptosis in KB human oral cancer cells. DIM-pPhBr and DIM-pPhF decreased cell proliferation and induced apoptosis evidenced by western blot analysis, DAPI staining and sub-$G_1$ population. This provides the first evidence that DIM-pPhBr and DIM-pPhF originating from Cruciferous vegetables induce apoptotic cell death in human oral cancer cells to inhibit cancer cell proliferation.

• Tuberculosis and Respiratory Diseases
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• v.42 no.6
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• pp.846-854
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• 1995

Background: Cytokeratin 19 is a subunit of cytokeratin intermediate filament expressed in simple epithelia such as respiratory epithelial cells and their malignant counterparts. An immunoradiometric assay is available to detect a fragment of the cytokeratin, referred to as Cyfra 21-1 in the serum. This study was conducted to evaluate the clinical utility of this new marker in the diagnosis of lung cancer compared with established markers of squamous cell carcinoma antigen (SCC Ag) and carcino-embryonic antigen(CEA). In addition, we compared the diagnostic sensitivity and specificity of Cyfra 21-1 with those of SCC Ag in squamous cell carcinoma of the lung. We also measured the level of Cyfra 21-1 in the different stages of squamous cell carcinoma of the lung. Method: We measured Cyfra 21-1(ELSA-CYFRA 21-1), SCC Ag(ABBOTT SCC RIABEAD) and CEA(ELSA2-CEA) in 79 patients with primary lung cancer and in 78 persons as a comparison group including 32 patients with pulmonary tuberculosis, 23 patients with benign lung disease and 23 cases with healthy individual. Cyfra 21-1 is measured by a solid-phase immunoradiometric assay(CIS Bio International, France) based on the two-site sandwich method. SCC Ag is measured by a radioimmunoassay(Abbott Laboratories, USA). CEA is measured by a immunoradiometric assay(CIS Bio International, France). All data were expressed as the mean$\pm$standard deviation. Results: 1) The mean value of Cyfra 21-1 was $18.38{\pm}3.65\;ng/mL$ in the lung cancer and $1.l6{\pm}0.53\;ng/mL$ in the comparison group(p<0.0001). SCC Ag was $3.53{\pm}6.06\;ng/mL$ in the lung cancer and $1.19{\pm}0.5\;ng/mL$ in the comparison group(p<0.01). CEA was $35.03{\pm}13.9\;ng/mL$ in the lung cancer and $2.89{\pm}1.01\;ng/mL$ in the comparison group(p<0.0001). 2) Cyfra 21-1 level in squamous cell carcinoma($31.52{\pm}40.13\;ng/mL$) was higher than that in adenocarcinoma($2.41{\pm}1.34\;ng/mL$)(p<0.0001) and small cell carcinoma($2.15{\pm}2.05\;ng/mL$)(p=0.007). SCC Ag level in squamous cell carcinoma($5.1{\pm}7.68\;ng/mL$) was higher than that in adenocarcinoma($1.36{\pm}0.69\;ng/mL$)(p=0.009) and small cell carcinoma($1.1{\pm}0.24\;ng/mL$) (p=0.024). 3) The level of Cyfra 21-1 was not correlated with the progression of stage in squamous cell carcinoma of the lung. 4) Using the cut-off value of 3.3ng/mL, the diagnostic sensitivity of Cyfra 21-1 was 83% in squamous cell carcinoma, 22% in adenocarcinoma and 17% in small cell carcinoma. The sensitivity of SCC Ag and CEA were 39% and 20%, respectively in squamous cell carcinoma, 11% and 39% in adenocarcinoma, and 0% and 33% in small cell carcinoma. 5) Comparison of the receiver operating characteristics curves(ROC curve) for Cyfra 21-1, SCC Ag and CEA revealed that Cyfra 21-1 showed highest diagnostic sensitivity among them in the diagnosis of lung cancer. Conclusion: Cyfra 21-1 is thought to be a better tumor marker for the diagnosis of lung cancer than SCC Ag and CEA, especially in squamous cell carcinoma of the lung.

• Tuberculosis and Respiratory Diseases
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• v.39 no.5
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• pp.400-406
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• 1992

Background: It has been known that see antigen was used in diagnosis of uterine cervical cancer and also known to be higher in squamous cell lung cancer. There has been no report about see antigen in squamous cell lung cancer in Korea. This study was designed to evaluate the usefulness of see antigen as a diagnostic tool and index for follow up after treatment. Method: The serum level of see antigen was measured in 12 cases with squamous cell lung carcinoma, 9 patients with other types of lung cancer, 7 patients with benign lung disease and 7 normal subjects by radioimmunoassay with Abott see Riabeap radioimmunoassay kit. We also measured see antigen after treatment in 6 patients who had received chemotherapy or sugery. Result: 1) The level of see antigen ($mean{\pm}1$ SD) was $2.27{\pm}1.53$, $0.67{\pm}0.38$, $0.62{\pm}0.53$, $0.53{\pm}0.36\;ng/ml$ respectively. 2) The see antigen activity in squamous cell lung carcinoma according to stage were as gollows. I; $2.07{\pm}1.56$, $III_a$; $5.04{\pm}0.53$ $III_b$; $1.94{\pm}0.7$ IV; $1.07{\pm}0.64$ (ng/ml). 3) In squamous cell lung cancer, 5 of 12 (42%) cases was shown more than 2.0 ng/ml see antigen. (sensitivity; 42%), but there was no case in any other type of lung cancer, benign lung disease, and in control groups (specificity; 100%). 4) The serum sec antigen level after treatment was significantly decreased in patients with partial or complete remission (p<0.01). Conclusion; It was suggested that see antigen might be used as a useful tumor marker for the response of treatment and assessment of prognosis in squamous cell lung cancer, but further study should be performed for the clinical use of see antigen.

• Journal of Life Science
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• v.29 no.3
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• pp.295-302
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• 2019

Liquiritigenin (LG) is a chiral flavonoid isolated from the roots of licorice. It exhibits multiple biological activities including anti-oxidant, anti-cancer, and anti-inflammatory effects. In particular though, the anti-cancer activity of LG in oral squamous cell carcinoma has yet to be elucidated, and LG-induced apoptosis in oral squamous cell carcinoma remains poorly understood. In the present study, we tested the role of LG in inducing apoptosis in oral squamous cell carcinoma cells. LG treatment of HN22 cells resulted in a dose-dependent inhibition of cell viability as detected by a 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide assay. The induction of apoptosis in terms of Annexin V/7-Aminoactinomycin D staining, sub-G1 population, and multi-caspase activity were assessed with a $Muse^{TM}$ Cell Analyzer. Flow cytometric analysis revealed that LG treatment resulted in G2/M arrest in cell cycle progression and downregulation of cyclin B1 and CDC2 expression in a concentration-dependent manner. It also resulted in significant upregulation of p27. In addition, LG was seen to trigger the generation of reactive oxygen species and induce CCAAT/enhancer-binding protein homologous protein and 78-kDa glucose-regulated protein in concentration-dependent upregulation. The LG treatment of HN22 cells led to a loss of mitochondrial membrane potential (${\Delta}{\Psi}m$); it also reduced the levels of anti-apoptotic protein and increased the expression of apoptotic protease activating factor-1, cleaved poly (ADP-ribose)polymerase and Bax. Overall, our results indicate that the pro-apoptotic effects of LG in HN22 cells depend on the activation of both intrinsic and extrinsic signaling pathways. Thus, our results suggest that LG constitutes a natural compound with a potential role as an anti-tumor agent in oral squamous cell carcinoma.

• Tuberculosis and Respiratory Diseases
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• v.49 no.4
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• pp.474-485
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• 2000

Background : Current studies on multimodal strategy for N2 non-small cell lung cancer are being high interest, have drawn much attention. N2 lung cancer, however, is composed of is divided into several sub groups with that have different prognoses. The prognostic factors still remain controversial. Methods : Between January 1990 and June 1999, 180 patients with N2 lung cancer who underwent surgical resection were investigated, excluding 10 of these for surgical mortality. All patients underwent mediastinal lymph node dissection. 20 clinicopathologic factors were investigated by univariable and multivariable analyses to identify significant prognostic factors among resected N2 disease. Results : The overall 5-year survival rate was 20.6%. Multivariable analyses among overall patients revealed 3 significant prognostic factors : Age, Histologic type, Vascular invasion. Based on the result, 49 patients with both age more than 60 and pathologic Non-squamous cell showed a 5-year survival of 5.0%, whereas 37 patients with neither of the factors showed a 5-year survival of 56.6%(p<0.001). And 12 patients with both vascular invasion and pathologic Non-squamous cell showed a 5-year survival of 11.9%, whereas 67 patients with neither of the factors showed a 5-year survival of 33.6%(p=0.01). Conclusion : The prognosis of surgically resected N2 disease varies according to the 3 significant prognosis factors. Tumor size may be an additional influencing factor in the prognosis of N2 disease.

• Proceedings of the KOR-BRONCHOESO Conference
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• 1993.05a
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• pp.85-85
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• 1993

The clinical staging system for laryngeal cancers is not sufficient for prognosticator due to different biologic characteristics and their microenvironment according to primary sites. For determining the prognosticators, the authors peformed immunohistochemical staining to EGFR, p53 protein, and pRB in 40 cases of surgically treated squamous cell carcinomas of larynx in our institute during the past 5 years. The results are as followings; 1. The positive expression rate of p53 protein and negative expression rate of pRB showed correlations with clinical parameters. 2. The three-year survival rate for p53 protein positive cases was worse than the p53 protein negative cases. 3. Expression rate of EGFR was not correlated with the clinical parameters. As a conclusion, expression rates of p53 protein and pRB not only reflect well the biologic behavior of laryngeal cancer, but correlate closely with the tumor factors. Therefore they may be useful as the prognosticator to predict the malignant potency of laryngeal squamous cell carcinomas.

• Journal of Oral Medicine and Pain
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• v.34 no.3
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• pp.261-276
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• 2009

Lactacystin, a microbial natural product synthesized by Streptomyces, has been commonly used as a selective proteasome inhibitor in many studies. Proteasome inhibitors is known to be preventing the proliferation of cancer cells in vivo as well as in vitro. Furthermore, proteasome inhibitors, as single or combined with other anticancer agents, are suggested as a new class of potential anticancer agents. This study was undertaken to examine in vitro effects of cytotoxicity and growth inhibition, and the molecular mechanism underlying induction of apoptosis in SCC25 human tongue sqaumous cell carcinoma cell line treated with lactacystin. The viability of SCC25 cells, human normal keratinocytes (HaCaT cells) and human gingiva fibroblasts (HGF-1 cells), and the growth inhibition of SCC25 cells were assessed by MTT assay and clonogenic assay respectively. The hoechst staining, hemacolor staining and TUNEL staining were conducted to observe SCC25 cells undergoing apoptosis. SCC25 cells were treated with lactacystin, and Western blotting, immunocytochemistry, confocal microscopy, FAScan flow cytometry, MMP activity, and proteasome activity were performed. Lactacystin treatment of SCC25 cells resulted in a time- and does-dependent decrease of cell viability and a does-dependent inhibition of cell growth, and induced apoptotic cell death. Interestingly, lactacytin remarkably revealed cytotoxicity in SCC25 cells but not normal cells. And tested SCC25 cells showed several lines of apoptotic manifestation such as nuclear condensation, DNA fragmentation, the reduction of MMP and proteasome activity, the decrease of DNA contents, the release of cytochrome c into cytosol, the translocation of AIF and DFF40 (CAD) onto nuclei, the up-regulation of Bax, and the activation of caspase-7, caspase-3, PARP, lamin A/C and DFF45 (ICAD). Flow cytometric analysis revealed that lactacystin resulted in G1 arrest in cell cycle progression which was associated with up-regulation in the protein expression of CDK inhibitors, $p21^{WAF1/CIP1}$ and $p27^{KIP1}$. We presented data indicating that lactacystin induces G1 cell cycle arrest and apoptois via proteasome, mitochondria and caspase pathway in SCC25 cells. Therefore our data provide the possibility that lactacystin could be as a novel therapeutic strategy for human tongue squamous cell carcinoma.

• Journal of the Korean Society of Food Science and Nutrition
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• v.32 no.5
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• pp.758-763
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• 2003

Amino acid transporters play an important role in supplying nutrients to normal and cancer cells for cell proliferation. System L is a major transport system responsible for the N $a^{＋}$-independent, large neutral amino acids including several essential amino acids. L-type amino acid transporter 1 (LAT1), an isoform of system L amino acid transporter, is highly expressed presumably to support their continuous growth and proliferation in malignant tumors. 2-Aminobicyclo- (2,2,1) -heptane-2-carboxylic acid (BCH) is a model compound for study of amino acid transporter as a system L selective inhibitor. In the present study, we examined whether BCH induced growth inhibition in KB human oral squamous carcinoma cell line or not. The uptake of L-［$^{14}$ C］leucine by KB cells is inhibited by BCH in a concentration dependent manner with a Ι $C_{50}$ value of 75.3$\pm$6.2 ${\mu}{\textrm}{m}$ and a $K_{i}$ value of 98.7$\pm$ 4.1 ${\mu}{\textrm}{m}$. The growth of KB cells is inhibited by BCH in time dependent manner and concentration dependent manner with a Ι $C_{50}$ value of 11.1 $\pm$0.8 mM. In the DNA of KB cells treated with the various concentrations and various periods of BCH, the characteristic ladders associated with DNA fragmentation were not observed. These results suggest that BCH inhibits the growth of KB oral epidermoid carcinoma cells through the inhibition of transport of neutral amino acids into cells without DNA break down. This phenomenon will be a new rationale for anti-cancer therapy.y.

• Journal of Gastric Cancer
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• v.6 no.1
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• pp.31-35
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• 2006

Purpose: A primary adenosquamous carcinoma of the stomach is relatively rare, accounting for only about 0.5% of all gastric cancers. However, its histopathologic characteristics are still unclear, and the most appropriate form of therapy has not been established yet. Materials and Methods: We retrospectively reviewed the clinicopathologic features of 8 patients with pathologically confirmed primary adenosquamous carcinomas out of 8,268 patients who underwent gastric cancer surgery at Samsung Medical Center between September 1994 and December 2004. Results: The median age of the 8 patients was 49 ($41{\sim}69$) years, and the male : female ratio was 5 : 3. In 3 patients, the tumor was located at the mid body of the stomach, and in 5 patients, at the lower body or antrum. The tumor sizes were $2.5{\sim}8cm$. Seven patients showed metastases to the regional lymph nodes. The UICC stage distribution were: 5 stage II, 2 stage III, and 1 stage IV. In the stage IV patient, a palliative gastrojejunostomy was performed, and he died 5 months after surgery. Of the 7 patients who underwent a radical gastrectomy and adjuvant chemotheratpy, the median survival was 34 ($12{\sim}66$) months, 2 patients died of cancer recurrence, and 4 patients are being followed up without evidence of recurrence. Conclusion: As for an adenocarcinoma of the stomach, a radical gastrectomy including regional lymph node dissection and postoperative adjuvant therapy should be performed for appropriate treatment of an adenosquamous carcinoma of the stomach.