• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• 제44권4호
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• pp.182-190
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• 2018

Objectives: Head and neck squamous cell carcinoma (HNSCC) is the sixth most common malignancy worldwide. Inconsistency in various histopathologic features for predicting nodal metastasis and overall prognosis and a better understanding of molecular mechanisms of tumourigenesis have shifted the focus to a search for more definitive predictive markers. To identify the role of two immunohistochemical (IHC) markers, E-cadherin and cyclin D1, as predictive markers of aggressiveness in HNSCC and to assess clonal expansion of tumour cells. Materials and Methods: A total of 66 cases of HNSCC with neck node dissection were studied. IHC was performed on primary tumour sections and lymph nodes showing metastatic deposits. Histopathological parameters such as tumour grade and TNM stage together with nodal status were compared according to expression of the two markers. Fischer's chi-square test was used to assess the correlation between the two markers and histopathological parameters. Results: Out of 66 cases studied, 37 showed LN metastasis. Most of the patients were male, and the most common tumour site was buccal mucosa. We found a significant association between loss of E-cadherin and node metastasis (P<0.001) and higher TNM stage (P<0.001). Cyclin D1 overexpression was significantly associated with only nodal metastasis (P=0.007). No significant association with tumour grade was found for either marker. The subgroup of E-cadherin loss with cyclin D1 overexpression was associated with the maximum incidence of nodal metastasis and higher TNM stage, highlighting the importance of using a combination of these two markers. A significant association was noted between the expression of markers at the primary site and at nodal deposits, indicating clonal expansion. Conclusion: A combination of the two markers E-cadherin and cyclin D1 can predict prognosis in HNSCC, although tumour heterogeneity may affect this association in some cases.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• 제26권6호
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• pp.581-590
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• 2000

Alterations in the cellular genome affecting the expression or function of genes controlling cell growth and differentiation are considered to be the main cause of cancer. Over 30 oncogenes can be activated by insertional mutagenesis, single point mutations, chromosomal translocations and gene amplification. The ras oncogenes have been detected in $15{\sim}20%$ of human tumors that include some of the most common forms of human neoplasia and are known to acquire their transforming properties by single point mutations in two domains of their coding sequences, most commonly in codons 12 and 61. The ras gene family consists of three functional genes, N-ras, K-ras and H-ras which encode highly similar proteins of 188 or 189 amino acid residues generically known as P21. ras proteins have been shown to bind GTP and GTP, and possess intrinsic GTPase activity. Experimental study was performed to observe the mutational change of the ras gene family and apply the results to the clinical activity. 36 Golden Syrian Hamster each weighing $60{\sim}80g$ were used and painted with 0.5% DMBA by 3 times weekly on the right buccal cheek(experimental side) for 6, 8, 10, 12, 14 and 16 weeks. Left buccal cheek (control side) was treated with mineral oil as the same manner of the right side. The hamsters were sacrificed on the 6, 8, 10, 12, 14 & 16 weeks. Normal and tumor tissues from paraffin block were completely dissected by microdissection and DNA from both tissue were isolated by proteinase K/phenol/chloroform extraction. Segments of the K-ras and H-ras gene were amplified by PCR using the oligonucleotide primers corresponding to the homologous region (codon 12 and 61) of the hamster gene, and then confirmational change of ras genes was observed by SSCP and autosequencing analysis. The results were as follows : 1. Malignant lesion could be found in the experimental side from the experimental six weeks. 2. One hamster among six showed point mutation of the H-ras codon 12($G{\rightarrow}A$ transition) at the experimental 10 and 14 weeks. 3. One of six at 6 weeks, two of six at 8 weeks and one of six at 12 weeks revealed the confirmational change of the H-ras codon 61($A{\rightarrow}T$ transversion). 4. The incidence of point mutation of H-ras codon 12 and 61 were 5.5%(2 of 36) and 11%(4 of 36) respectively. 5. Point mutation of the K-ras could not be seen during the whole experimental period. Form the above results, these findings strongly support the concept that H-ras oncogenes may have the influence of the DMBA induced carcinoma of hamster buccal pouch.

• 한국작물학회지
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• 제51권spc1호
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• pp.1-6
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• 2006

Tocotrienol의 건강식품 및 의료용 가공품으로의 고부가가치화 가능성을 평가하기 위하여 미강에서 추출한 tocotrienol의 항암 효과 및 독성평가를 실시하였다. HepG2 간암 세포를 대상으로 한 항암효과 분석 결과 tocotrienol이 간암세포의 증식을 억제함을 입증할 수 있었다. 또한 랫드를 이용한 경구독성 검사를 수행한 결과 tocotrienol 최종 생산물은 경구투여 한계량인 $2,000mg\;kg^{-1}$ 수준에서도 사망률, 일반 증상, 체중 변화 등에 이상을 보이지 않았으며, 부검 후 흉강 및 복강의 모든 장기에 대한 육안적 부검 소견 등에서도 아무런 독성학적 변화가 유발되지 않음을 알 수 있었다.

• Journal of Preventive Medicine and Public Health
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• 제50권4호
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• pp.251-261
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• 2017

Objectives: This study aimed to predict the 10-year impacts of the introduction of pictorial warning labels (PWLs) on cigarette packaging in 2016 in Korea for adults using DYNAMO-HIA. Methods: In total, four scenarios were constructed to better understand the potential health impacts of PWLs: two for PWLs and the other two for a hypothetical cigarette tax increase. In both policies, an optimistic and a conservative scenario were constructed. The reference scenario assumed the 2015 smoking rate would remain the same. Demographic data and epidemiological data were obtained from various sources. Differences in the predicted smoking prevalence and prevalence, incidence, and mortality from diseases were compared between the reference scenario and the four policy scenarios. Results: It was predicted that the optimistic PWLs scenario (PWO) would lower the smoking rate by 4.79% in males and 0.66% in females compared to the reference scenario in 2017. However, the impact on the reduction of the smoking rate was expected to diminish over time. PWO will prevent 85 238 cases of diabetes, 67 948 of chronic obstructive pulmonary disease, 31 526 of ischemic heart disease, 21 036 of lung cancer, and 3972 prevalent cases of oral cancer in total over the 10-year span due to the reductions in smoking prevalence. The impacts of PWO are expected to be between the impact of the optimistic and the conservative cigarette tax increase scenarios. The results were sensitive to the transition probability of smoking status. Conclusions: The introduction of PWLs in 2016 in Korea is expected reduce smoking prevalence and disease cases for the next 10 years, but regular replacements of PWLs are needed for persistent impacts.

• Asian Pacific Journal of Cancer Prevention
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• 제14권8호
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• pp.4769-4774
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• 2013

This paper is the first to present the incidence and overall survival of patients with squamous cell carcinoma of the head and neck (SCCHN) from the extreme northern part of the Philippines. We retrospectively retrieved the records of patients with histologically-confirmed squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx and larynx at the Mariano Marcos Memorial Hospital and Medical Center, Ilocos Norte, Philippines, from 2003 to 2012 and analysed prognostic factors associated with survival. Of the 150 cases, only 80 (53.3%) were still living when the study was terminated. Median age at initial diagnosis was 61.5 years and the male to female ratio was 7:3. The majority of the cases had tumours in the oral cavity (50.7%), followed by the larynx (36.7%). Sex (log rank=1.94, p value/${\alpha}$=0.16), tumor site (log rank=0.02, p value/${\alpha}$=0.90), tumor grade (log rank=1.74, p value/${\alpha}$=0.42), and node stage (log rank=0.07, p value/${\alpha}$=0.80) were not shown to be associated with the survival of our cases. Only 45 (30.0%) had no regional lymph node involvement (N0) at presentation and 12 (8.0%) had already developed distant metastases. Among the 150 patients, 71 (47.3%) were not able to receive treatment of any kind. Oddly, treatment (log rank=1.65, p value/${\alpha}$=0.20) was also shown to be not associated with survival. The survival rate of those who underwent surgery, radiotherapy, or both was not statistically different from those who did not receive any treatment. Only the tumor stage (log rank=4.51, p value/${\alpha}$=0.03) was associated with patient survival. The overall mean survival was 49.3 months, with survival rate diminishing from 88.3% during the 1st year to 1.80% by end of the study. This relatively low survival rate of our cases only reflects their poor access to quality diagnostic and treatment facilities.

• 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.

• Radiation Oncology Journal
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• 제15권3호
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• pp.225-231
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• 1997

목적 : 두경부암 환자에서 수술 및 수술 후 방사선치료가 갑상선 기능에 미치는 영향을 평가하기 위하여 전향적 연구를 시행하였다. 대상 및 방법 : 1986년 9월부터 1994년 12월까지 수술후 방사선치료를 받은 두경부암 환자 중 추적 관찰이 가능했던 71예를 대상으로 하였다. 환자의 연령분포는 32세부터 73세였고, 중간값은 58세였으며, 여자 12예, 남자 59예였다. 원발 병소부위는 후두가 34예로 가장 많았고, 구강 12예, 구인두 1예, 하인두 13예, 상악동 2예, 타액선 3예, 근원 불명 전이성 경부암 6예였다. 전후두절 제술 및 경부곽청수술을 시행한 환자는 45예였고, 경부곽청수술만 시행한 환자는 26예였다. 모든 환자에 대하여 방사선치료 전 및 방사선치료 후에 정기적으로 임상검사 및 갑상선 기능검사 (T3, T4, free T4, TSH, antithyroglovulin antibody, antimicrosomal antibody)를 시행하였다. 방사선량은 40.6Gy에서 60Gy였고 중간값은 50Gy였으며 추적관찰 기간은 3개월에서 80개월이었다. 결과 : 갑상선 기능 이상의 빈도는 $56.3\%(40/71)$였다. 31예 $(43.7\%)$는 갑상선 기능이 정상이었고 7예 $(9.9\%)$는 임상적 갑상선 기능저하증이었으며 33예 $(46.5\%)$는 준임상적 갑상선 기능저하증이었다. 갑상선 기능항진증, 갑상선 결절, 악성종양은 발견되지 않았다. 경부곽청수술군보다 전후두절제술 및 경부곽청수술군에서 갑상선 기능 이상이 일찍 발생하였다(p<0.05). 방사선치료 후 갑상선 기능 이상의 발생 빈도에 영향을 준 위험인자는 전후두절제술 및 경부곽청수술과 방사선치료의 병용요법 (P=0.0000)이었다. 전후두절제술 및 경부곽청수술군 45예 중 36예 $(80\%)$에서 갑상선 기능 이상이 발생하였으며 경부곽청수술군 26예 중 4예 $(15.4\%)$에서만이 갑상선 기능이상이 발생하였다. 결론 : 두경부암 환자에서 수술 및 방사선치료 후 갑상선 기능 이상은 비교적 흔한 합병증이며, 갑상선 기능 이상의 발생 빈도에 영향을 미치는 인자는 전후두절제술 및 경부곽청수술과 방사선치료의 병용요법이었다. 갑상선 기능 이상을 조기에 발견하여 치료하기 위하여 방사선치료 전 및 방사선치료 후에 정기적인 갑상선 기능검사가 필요할 것으로 사료된다.

• Radiation Oncology Journal
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• 제28권2호
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• pp.64-70
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• 2010

목 적: 국소 진행된 두경부암 환자에서 방사선치료를 포함한 근치적 치료 후 갑상샘기능저하증의 발생률을 분석하고자 후향적 연구를 실시하였다. 대상 및 방법: 2000년 1월부터 2005년 12월까지 본원에서 국소 진행된 두경부암으로 진단받고 근치적 목적으로 방사선치료 단독 또는 수술 후 방사선치료를 받은 환자 중 수술로 갑상샘을 절제하지 않았고, 방사선치료 전 갑상샘기능이 정상이며, 하부 경부림프절이 방사선치료 범위에 포함된 115명의 환자를 대상으로 본 연구를 시행하였다. 환자의 중앙연령은 59세(28~85세)이고 남자 73명, 여자 42명이었다. 원발병소의 위치는 구강, 구인두, 하인두, 후두, 그 외가 각각 18, 40, 28, 22, 7명이었으며, 편측 경부절제술을 받은 환자가 19명(16.5%), 양측 경부절제술을 받은 환자가 18명(15.7%), 방사선치료만을 시행한 환자가 78명(67.8%)이었다. 방사선치료는 6-MV X-ray를 사용하였으며, 통상 분할 조사법에 의해 하루 1.8~2 Gy 씩, 주 5회 조사하였다. 원발병소에 조사된 방사선량은 중앙값 70.2 Gy (59.4~79.4 Gy)이었으며, 하부 경부림프절에 조사된 방사선량은 중앙값 50.0 Gy (44.0~66.0 Gy)이었다. 추적관찰기간은 2~91개월이었으며, 중앙값은 29개월이었다. 결 과: 전체 115명 환자 중에서 38명(33.0%)의 환자에서 갑상샘기능저하증이 관찰되었다. 전체 환자의 1년, 3년의 갑상샘기능저하증 발생률은 각각 28.7% (33명), 33.0% (38명)이었으며, 갑상샘기능저하증 발생시기의 중앙값은 8.5개월(0~36개월)이다. 갑상샘기능저하증 발생에 영향을 주는 인자로 단변량분석결과 경부절제술 여부가 위험인자로 분석되었으나, 다변량분석에서는 통계적으로 유의한 관련 인자는 없었다. 결 론: 두경부 종양환자의 방사선치료를 포함한 근치적 치료 후 갑상샘기능저하증이 발생할 수 있으며, 대부분이 1년 이내 발생하므로 치료 후 갑상샘기능검사를 정기적으로 실시할 필요가 있다. 특히 경부 림프절제술 후 방사선 치료를 시행하는 경우 더욱 주의하여 갑상샘기능저하증의 발생을 확인해야 한다.

• 한국식품영양학회지
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• 제21권4호
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• pp.397-402
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• 2008

Over the past few years, anthocyanin has been demonstrated to exert potentially anti-oxidative and bioavailability effects including anti-cardiovascular disease and cancer-preventive effects in humans. This study was conducted to assess the toxicity of anthocyanin extracts from black soybean seed coats via oral administration in a mice feeding test. The final anthocyanin-containing products induced signs of toxicity on mortality in the 4-week feeding test. The incidence of clinical signs and changes in body and organ weight were also not observed in all anthocyanin-treated groups as compared with the control groups. In hematology analysis, RBC indices concluding MCV, MCH, and MCHC and WBC differential counting such a NEU, LYM, MONO, EOS, and BASO evidenced no significant differences between the anthocyanin treatment and control groups. The biochemical parameters in serum analysis - ALT, AST, BUN, Crea etc.- were also not significantly altered in those groups. Absolute and relative organ weights were not increased after 4 weeks of treatment with anthocyanin extracts in mice. In conclusion, anthocyanin extracts from the black soybean has biological activity without any toxic effects, which also suggests that the consumption of soy containing anthocyanin products may be a good source for health and medical supplies.

• Journal of Microbiology and Biotechnology
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• 제24권8호
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• pp.1143-1147
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• 2014

Human papillomavirus (HPV) infection is considered to play a critical role in the development of cervical carcinoma, which is the third most common cancer among Korean females. Here, we performed a baseline study of HPV infection and genotyping using an HPV DNA chip, which is a type of oligonucleotide microarray. A total of 6,855 cervical swab specimens from 5,494 women attending Dankook University Hospital Health Improvement Center in Cheonan, Korea between 2006 and 2012, originally collected for HPV infection screening, were genotyped for HPV. The extracted DNA from the cervical specimens was investigated by an HPV DNA chip designed to detect 41 different HPV types. HPV was identified as positive in 1,143 (16.7%) of the 6,855 samples. The most frequently detected HPV genotypes were HPV types 16, 53, 56, 58, 39, 52, 70, 84, 68, 62, 35, 54, 81, 18, and 30, in descending order of incidence. The proportions of single and multiple HPV infections in the HPV-positive specimens were 78.1% and 21.9%, respectively. The average age of HPV-positive patients was 39.9 years, with the positive rate of HPV being the highest in the 10-29 age group (20.6%). We report here on the prevalence and distribution of 41 different genotypes of HPV according to age among women in Cheonan, Korea. These data may be of use as baseline data for the assessment of public health-related issues and for the development of area-specific HPV vaccines.