• Imaging Science in Dentistry
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• 제31권3호
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• pp.135-143
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• 2001

Purpose : To evaluate the effect of all-trans-retinoic acid on radiosensitivity and radiation-induced apoptosis in NHOK, HEp-2 and FaDu cell lines. Material and Methods: We measured the changes in survival fraction at 2 Gy (SF2), α and β after treatment of retinoic acid (1μM) prior to irradiation with doses of 2, 4, 6 and 10 Gy and correlated the radiosensitizing effect of retinoic acid with them. Also, apoptosis induction was assayed with the flow cytometry on days 1,2, 3, 4 and 5 after irradiation (2, 10 and 20 Gy) combined with retinoic acid. Results and Conclusion: SF2 values for NHOK, HEp-2 and FaDu cell lines were 0.54, 0.64 and 0.41, respectively and the cell line of FaDu was the most radiosensitive. For cell lines of NHOK and HEp-2, pretreatment of cells with retinoic acid resulted in a significant decrease of the SF2 values. The α/β ratios of x-ray survival curve were 8.714 (NHOK), 4.098 (HEp-2) and 11.79 (FaDu). The α/β ratio for NHOK decreased on pretreatment with retinoic acid, whereas those for HEp-2 and FaDu increased. Radiation induced apoptosis in all cell lines but, retinoic acid did not affect the apoptosis.

• Radiation Oncology Journal
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• 제28권1호
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• pp.9-15
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• 2010

목 적: 진행된 두경부암 환자들에서 근치적 방사선치료 후 완전반응을 보인 경부 림프절 병변에서의 재발 빈도와 양상을 확인하고, 이의 임상적 의미를 알아보고자 이 연구를 진행하였다. 대상 및 방법: 1987년부터 2008년까지 원발성 두경부 상피세포암종 및 경부 림프절 종대 병변에 대해 근치적 방사선치료를 받았던 환자들의 임상자료를 분석하였다. 이들 중 경부 림프절 병변에 충분한 방사선조사를 받은 후 완전 반응으로 평가된 환자들을 최종 연구대상으로 선정하였다. 대상 환자들의 주기적 영상자료를 바탕으로 경부 림프절에서의 재발 빈도와 양상을 확인하였다. 아울러 재발률과 관련된 예후인자들도 분석하였다. 결 과: 방사선치료 후 경부 림프절에서 완전반응으로 평가된 환자들은 73명이었다. 이들의 추적관찰 기간 동안의 재발률은 19.2%였다. 원발 병변에서도 완전반응을 보인 55명에서의 경부 재발률은 5.5%였다. 경부 재발의 80% 이상이 3년 이내에 확인되었으며, 47%에서 원발 병변의 재발이나 진행과 관련이 있었다. 치료 후 원발 병변의 반응 정도와 방사선 모의치료 방법이 경부 림프절 재발률과 관련 있었다. 결 론: 방사선치료 후 원발 병변 및 경부 림프절 병변에서 완전반응으로 평가된 환자들에서의 경부 림프절 재발률은 약 5%로, 이들에서는 계획된 림프절 절제술 없이 정기적인 추적관찰이 가능할 것으로 판단된다.

• Maxillofacial Plastic and Reconstructive Surgery
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• 제22권2호
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• pp.164-173
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• 2000

The p16 protein is a cyclin dependent kinase inhibitor that inhibits cell cycle progression from $G_1$ phase to S phase in cell cycle. Many p16 gene mutations have been noted in many cancer-cell lines and in some primary cancers, and alterations of p16 gene function by DNA methylation have been noticed in various kinds of cancer tissues and cell-lines. There have been a large body of literature has accumulated indicating that abnormal patterns of DNA methylation (both hypomethylation and hypermethylation) occur in a wide variety of human neoplasma and that these aberrations of DNA methylation may play an important epigenetic role in the development and progression of neoplasia. DNA methylation is a part of the inheritable epigenetic system that influences expression or silencing of genes necessary for normal differentiation and proliferation. Gene activity may be silenced by methylation of up steream regulatory regions. Reactivation is associated with demethylation. Although evidence or a high incidence of p16 alterations in a variety of cell lines and primary tumors has been reported, that has been contested by other investigators. The precise mechanisms by which abnormal methylation might contribute to carcinogenesis are still not fully elucidated, but conceivably could involve the modulation of oncogene and other important regulatory gene expression, in addition to creating areas of genetic instability, thus predisposing to mutational events causing neoplasia. There have been many variable results of studies of head and neck squamous cell carcinoma(HNSCC). This investigation was studied on 13 primary HNSCC for p16 gene status by protein expression in immunohistochemistry, and DNA genetic/epigenetic analyzed to determine the incidence, the mechanisms, and the potential biological significance of its Inactivation. As methylation detection method of p16 gene, the methylation specific PCR(MSP) is sensitive and specific for methylation of any block of CpG sites in a CpG islands using bisulfite-modified DNA. The genomic DNA is modified by treatment with sodium bisulfate, which converts all unmethylated cytosines to uracil(thymidine). The primers designed for MSP were chosen for regions containing frequent cytosines (to distinguish unmodified from modified DNA), and CpG pairs near the 5' end of the primers (to provide maximal discrimination in the PCR between methylated and unmethylated DNA). The two strands of DNA are no longer complementary after bisulfite treatment, primers can be designed for either modified strand. In this study, 13 paraffin embedded block tissues were used, so the fragment of DNA to be amplified was intentionally small, to allow the assessment of methylation pattern in a limited region and to facilitate the application of this technique to samlples. In this 13 primary HNSCC tissues, there was no methylation of p16 promoter gene (detected by MSP and automatic sequencing). The p16 protein-specific immunohistochemical staining was performed on 13 paraffin embedded primary HNSCC tissue samples. Twelve cases among the 13 showed altered expression of p16 proteins (negative expression). In this study, The author suggested that low expression of p16 protein may play an important role in human HNSCC, and this study suggested that many kinds of genetic mechanisms including DNA methylation may play the role in carcinogenesis.

• 생명과학회지
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• 제19권6호
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• pp.770-780
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• 2009

녹조류인 Spirulina platensis에서 추출하여 만든 새로운 광감작제와 660 nm의 다이오드 레이저를 이용한 광역학치료의 항암효과와 치료기전을 알아보았다. 세포 독성능은 MTT assay를 이용하였고, 세포사멸기전은 propidium iodide과 Hoechst 33342 염색법과 투과전자현미경으로 확인하였다. 또한 암세포가 이종 이식된 누드마우스 모델에서 광역학치료를 시행하여 항암효과를 확인하였다. 3종류의 클로로필 유도체 중 9-hydroxypheophorbide-a (9-HpbD-a)의 세포 독성능이 가장 우수하였고, 9-HpbD-a의 적정 레이저조사 시간은 30분 (3.2 J/$cm^{2}$), 광감작제를 투여하고 레이저조사시간까지의 배양시간은 최소 6시간 이상임을 확인하였다. 광역학치료의 세포사멸기전은 낮은 9-HpbD-a 농도에서 세포고사가 주된 세포사멸기전이었고, 높은 농도의 9-HpbD-a에서는 세포괴사에 의한 세포사멸이 주된 기전임을 확인하였다. 투과전자현미경 하에서도 같은 양상을 관찰하였다. 그리고 암세포가 이종 이식된 누드마우스 모델에서의 광역학치료는 제1군 정상대조군과 제2군 9-HpbD-a만을 투여한 종양조직모두 지속적인 종양의 성장(100% )을 보였고, 제3군인 레이저만을 종양조직에 조사한 실험군에서는 3 마리는 치료가 되지 않았고(75.0%), 1 마리는 재발(25.0%) 하였다. 제4군 광역학치료군에서 총16 마리의 종양에서 10 마리는 완치(62.5%), 4 마리는 재발(25.0%), 2 마리는 치유되지 않았음(12.5% )을 확인하였다. 9-HpbD-a와 660 nm 다이오드 레이저를 이용한 광역학치료는 유의한 항암효과를 나타내었고 9-HpbD-a를 이용한 광역학치료는 새로운 치료방법으로서 향후 암치료의 유용한 치료방법으로 기대된다.

• Asian Pacific Journal of Cancer Prevention
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• 제14권10호
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• pp.5965-5972
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• 2013

PIN1 is one member of the parvulin PPIase family. By controlling Pro-directed phosphorylation, PIN1 plays an important role in cell transformation and oncogenesis. There are many polymorphisms in the PIN1 gene, including rs2233678 and rs2233679 affecting the PIN1 promoter. Recently, a number of case-control studies were conducted to investigate the association between PIN1 gene rs2233678 and rs2233679 polymorphism and cancer risk. However, published data are still conflicting. In this paper, we summarized data for 5,427 cancer cases and 5,469 controls from 9 studies and attempted to assess the susceptibility of PIN1 gene polymorphism to cancers by a synthetic meta-analysis. Odds ratios (ORs) with 95% confidence intervals (CIs) were estimated to assess the relationship. All analyses were performed using Stata software. Our results suggested that rs2233678 represented a protective factor in overall analysis (CC vs GG: OR= 0.697, 95%CI: 0.498-0.976; CG vs GG: OR=0.701, 95%CI: 0.572-0.858; Dominant model: OR= 0.707, 95%CI: 0.590-0.847; C allele vs G allele: OR=0.734, 95%CI: 0.623-0.867) and especially for squamous cell carcinoma of the head and neck, lung cancer and breast cancer in Asians and Caucasians. The rs2233679 polymorphism was significantly associated with decreased cancer risk in overall analysis (CT vs CC: OR=0.893, 95%CI=0.812-0.981; Dominant model: OR=0.893, 95%CI=0.816-0.976; T allele vs C allele; OR=0.947, 95%CI=0.896-1.000) and especially in Asians. In conclusion, our meta-analysis suggested that -842G>C (rs2233678) and -667C>T (rs2233679) may contribute to genetic susceptibility for cancer risks. Further prospective research with larger numbers of worldwide participants is warranted to draw comprehensive and firm conclusions.

• 대한방사선치료학회지
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• 제18권1호
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• pp.21-28
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• 2006

목 적: 10 MV X-선의 선형가속기를 이용하여 두경부종양 및 임파선 전이 환자를 치료할 시 피부표면 종양에 균일한 선량을 부여하기 위하여 조직 등가물질로 산란판을 제작하였으며 팬톰을 이용한 피부선량을 측정하여 그 효과를 평가하였다. 대상 및 방법: 조직 등가 물질인 lucite로 산란판을 제작하여 가속기의 콜리메이터와 피부사이에 부착하였으며 조사면적의 크기($5{\times}5{\sim}30{\times}30cm^2$)와 산란판 두께 및 피부와 산란판 간의 거리에 따른 피부 및 체표 0.4 cm에서의 선량 변화를 측정하였다. 또한 자체 제작한 산란 판의 체표 선량 증강 효과를 평가하기위해 볼루스를 이용한 체표 선량을 측정하여 그 효과를 비교하였다. 결 과: 10 MV X-선 선형가속기와 피부 사이에 산란판을 설치하여 피부선량이 증가 되었으며 산란판의 위치에 따라 피부선량이 변화되었고, 0.4 cm 깊이의 선량과 최대선량지점이 피부표면쪽으로 이동하였다. 산란판이 일정할 경우 조사면적이 커질수록 표면선량이 증가하고 최대 선량점은 피부표면 방향으로 이동하였다. 또한 산란판의 두께가 두꺼울수록 표면선량이 증가하고 최대 선량점은 피부표면 방향으로 이동하였다. 결 론: 10 MV X-선을 이용하여 두경부 종양 및 임파선 전이 암을 치료할 경우 산란판을 이용하여 이차산란 전자를 피부표면 앞에서 발생시킴으로써 표면근접부의 선량을 증가시켜 종양부위에 균일한 선량을 조사할 수 있었다. 본 연구에서는 조사면적에 따라 적정 산란판 조건을 찾아 임상에서 유용하게 사용하고자 하였으며, 1.2 cm, 1.8 cm 두께의 산란판을 피부로부터 7 cm에 위치 시켰을때 $10{\times}10cm^2$ 조사면적의 표면선량이 각각 60%, 64%로 측정되었고, 0.4 cm 깊이의 선량이 94%, 94%로 가장 이상적으로 관찰되었다.

• Korean Journal of Radiology
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• 제22권5호
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• pp.751-758
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• 2021

Objective: Preoperative differentiation between inverted papilloma (IP) and its malignant transformation to squamous cell carcinoma (IP-SCC) is critical for patient management. We aimed to determine the diagnostic accuracy of conventional imaging features and histogram parameters obtained from whole tumor apparent diffusion coefficient (ADC) values to predict IP-SCC in patients with IP, using decision tree analysis. Materials and Methods: In this retrospective study, we analyzed data generated from the records of 180 consecutive patients with histopathologically diagnosed IP or IP-SCC who underwent head and neck magnetic resonance imaging, including diffusion-weighted imaging and 62 patients were included in the study. To obtain whole tumor ADC values, the region of interest was placed to cover the entire volume of the tumor. Classification and regression tree analyses were performed to determine the most significant predictors of IP-SCC among multiple covariates. The final tree was selected by cross-validation pruning based on minimal error. Results: Of 62 patients with IP, 21 (34%) had IP-SCC. The decision tree analysis revealed that the loss of convoluted cerebriform pattern and the 20th percentile cutoff of ADC were the most significant predictors of IP-SCC. With these decision trees, the sensitivity, specificity, accuracy, and C-statistics were 86% (18 out of 21; 95% confidence interval [CI], 65-95%), 100% (41 out of 41; 95% CI, 91-100%), 95% (59 out of 61; 95% CI, 87-98%), and 0.966 (95% CI, 0.912-1.000), respectively. Conclusion: Decision tree analysis using conventional imaging features and histogram analysis of whole volume ADC could predict IP-SCC in patients with IP with high diagnostic accuracy.

• Asian Pacific Journal of Cancer Prevention
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• 제13권6호
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• pp.2629-2633
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• 2012

Background: Raw betel nut (RBN) chewing is an important contributing factor for esophageal squamous cell carcinoma (ESCC), although associated genomic changes remain unclear. One difficulty in assessing the effects of exclusively RBN induced genetic alterations has been that earlier studies were performed with samples of patients commonly using tobacco and alcohol, in addition to betel-quid. Both CDKN2A (at 9p21) and Rb1 gene (at 13q14.2) are regarded as tumor suppressors involved in the development of ESCC. Therefore, the present study aimed to verify the RBN's ability to induce ESCC and assess the involvement of CDKN2A and Rb1 genes. Methods: A panel of dinucelotide polymorphic markers were chosen for loss of heterozygosity studies in 93 samples of which 34 were collected from patients with only RBN-chewing habit. Promoter hypermethylation was also investigated. Results: Loss in microsatellite markers D9S1748 and D9S1749, located close to exon $1{\beta}$ of CDKN2A/ARF gene at 9p21, was noted in 40% ESCC samples with the habit of RBN-chewing alone. Involvement of a novel site in the 9p23 region was also observed. Promoter hypermethylation of CDKN2A gene in the samples with the habit of only RBN-chewing alone was significantly higher (p=0.01) than Rb1 gene, also from the samples having the habit of use both RBN and tobacco (p=0.047). Conclusions: The data indicate that the disruption of 9p21 where CDKN2A gene resides, is the most frequent critical genetic event in RBN-associated carcinogenesis. The involvement of 9p23 as well as 13q14.2 could be required in later stages in RBN-mediated carcinogenesis.

• Asian Pacific Journal of Cancer Prevention
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• 제16권10호
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• pp.4335-4338
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• 2015

Background: Oral cancer is the third most common malignancy in Saudi Arabia, the highest incidence of which is reported from Jazan province. The objective of this study was to evaluate the association of various locally used substances, especially shamma, with oral cancer in the Jazan region of Saudi Arabia. Materials and Methods: A hospital-based case-control study was designed and patient records were scanned for histologically confirmed oral cancer cases. Forty eight patients who were recently diagnosed with oral cancer were selected as cases. Two healthy controls were selected for each observed case and they were matched with age (+/- 5 years) gender and location. Use of different forms of tobacco such as cigarettes, pipe-smoking and shamma (smokeless-tobacco) was assessed. Khat, a commonly used chewing substance in the community was also included. Descriptive analysis was first performed followed by multiple logistic regression (with and without interaction) to derive odds ratios (ORs) and 95% confidence interval (CIs). Results: Mean age of the study sample (56% males and 44% females) was 65.3 years. Multinomial regression analysis revealed that shamma use increased the odds of developing oral cancer by 29 times (OR=29.3; 10.3-83.1). Cigarette (OR=6.74; 2.18-20.8) was also seen to have an effect. With the interaction model the odds ratio increased significantly for shamma users (OR=37.2; 12.3-113.2) and cigarette smokers (OR=10.5; 2.88-3.11). Khat was observed to have negative effect on the disease occurrence when used along with shamma (OR=0.01; 0.00 - 0.65). Conclusions: We conclude that shamma, a moist form of smokeless tobacco is a major threat for oral cancer occurrence in the Jazan region of Saudi Arabia. This study gives a direction to conduct further longitudinal studies in the region with increased sample size representing the population in order to provide more substantial evidence.

• Radiation Oncology Journal
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• 제13권1호
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• pp.9-18
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• 1995

목적 :상악동암의 적절한 치료 방법을 알기 위하여 후향적 분석을 시행하였다. 대상 및 방법 : 1986년 1월 부터 1992년 12월 까지 전남대학교 병원에서 치료받은 상악동에서 발생한 편평상피세포암 33명을 대상으로 하였다. 남자가 24명 여자가 9명이었고 연령의 중앙간은 55세였다. 1988년에 제시된 AJCC 병기 분류법에 따른 종양의 병기는 T2 1명, T3 10명, T4 22명이었으며 경부임파절 전이는 5명에서 관찰되었다(Nl:4명, N2b;1명). 치료방법에 따라 3군으로 분류하여 분석하였으며 첫 군(FAR 군으로 명명, 16명)은 수술전 경동맥 항암화학요법(5-FU, 평균 3078mg)과 방사선치료(평균 3433cGy) 및 비타민 A(50,000 IU. daily)를 병용하고 이어서 상악전적출술 과 술 후 방사선치료(평균 2351cGy)를 시행하였다. 방사선총량은 5255cGy였다. 둘째군(SR 군으로 명명, 7명)은 상악전적출술과 술후 방사선 치료(평균 5920cGy)를 시행하였다. 셋째군(R 군으로 명명, 6명)은 근치적 목적의 방사선 치료(평균 7164cGy)만 시행하였다. 생존율 분석에는 Kaplan-Meier법을 이용하였고 두 군간의 차이에 대한 검정은 Mantel-Cox법으로 하였다. 결과 : 국소종양 제어율은 2년에 FAR, SR, R군에서 각각 $100\%$, $50\%$, $27.7\%$로 나타났다. 무병생존율은 2년에 FAR, SR, R군에서 각각 $88.9\%$, $33.3\%$, $0\%$였다. 전체적인 생존율은 2년에 FAR, SR, R군에서 각각 $88.9\%$, $40\%$, $50\%$였다. FAR군과 SR군간에, 그리고 FAR군과 R군간에 국소종양 제어율, 2년 무병생존율, 2년 생존율에 있어서의 차이는 통계학적으로 유의하였다. 그러나 SR군과 R군간의 차이는 통계학적 유의성이 없었다. 결론 :수술전 경동맥 5-FU와 비타민 A 그리고 방사선 치료를 병용 치료하여 종양의 부분적 관해를 유도한 후 상악전적출술과 추가적인 방사선 치료를 시행한 FAR군이 상악전적출술후 방사선치료를 시행한 군이나 방사선 단독치료군보다 더 좋은 성적을 보였다. 앞으로 이에 대한 전향적 연구가 필요할 것으로 사료된다.