• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• 제26권4호
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• pp.337-344
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• 2000

본 연구에서는 MSI와 구강암과의 상관관계를 규명하기 위하여 17례의 구강암에 대하여 12종류의 marker를 이용하여 MSI 빈도를 조사하였으며, 동시에 p53단백의 과발현과 유전자 돌연변이 양상에 대해서도 알아보았다. 그 결과 4종류 이상의 marker에 대해서 MSI가 나타나는 widespread MSI의 경우 임상병리학적으로 뚜렷한 특징이 없었다. 또한 흡연과 MSI 빈도간에도 연관성이 없었으나 흡연은 p53 유전자의 돌연변이를 증가시켜 암화과정을 촉진하는 작용을 하는 것으로 나타났다.

• Radiation Oncology Journal
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• 제11권2호
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• pp.267-275
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• 1993

1985년 3월부터 1990년 9월까지 구강암으로 진단받고 본원 치료방사선과에서 방사선치료를 시행하였던 85명의 환자에 대한 치료결과를 후향적으로 분석하였다. 이중 방사선 단독치료가 37예였고 수술후 방사선치료가 48예였다. 방사선치료 방법으로는 70예에서 $^{60}Co$와 전자선에 의한 외부방사선조사로만 시행하였고 조직내삽입 복합요법이 7예, oral cone추가사용이 8예였다. 전체환자중 설암이 40예로 가장 많았고 구강저부암이 17예, 구개암이 12예, 후구치삼각부암을 포함한 치육암이 10예, 구협암이 5예, 구순암이 1예였다. 병리소견상 편평상피세포암이 77예로 가장 많았으며, AJC TNM 병기에 의한 병기 I+II기는 28예였고 병기 III+IV기 환자의 3년생존율은 각각 $60.9\%$와 $23.1\%$였다. 예후인자에 대한 분석상 원발병소의 크기가 유의하였다(P<0.01). 기타 나이, 원발병소의 위치, 림프절 전이여부, 치료방법(수술여부), 조사선량, 종양세포의 조직학적 등급 등에 의한 생존율과 국소제어율의 차이는 통계학적으로 유의한 결과를 얻을 수 없었다. 이중 치료방법에 따르면, 원발병소의 크기가 클수록, 혹은 림프절 전이여부를 막론하고 수술과 방사선 병용치료군에서 방사선 단독치료군보다 유의하지는 않았지만 더 높은 생존율을 보였다(p<0.1). 결론적으로 조기구강암에서는 방사선 단독치료가 수술과 방사선 병용치료에 비해 비슷한 치료성적을 보이면서도 특히 해부학적, 기능적 장애를 야기하는 수술에 비해 더 효과적이며 진행성구강암에서는 수술과 방사선 병용치료가 적절하다고 사료된다.반응율은 높으나 화학요법 및 방사선치료가 국소관해율 및 생존율의 향상으로는 연결되지는 않았다. 결론적으로 진행된 비인강암에서의 화학요법은 좀더많은 비교대조군 연구(controlled clinical trial)를 통해서만 역 할을 이야기할 수 있을 것으로 사료된다. performance status(KPS), 침습부위, 수술적 제거여부 및 제거정도, 방사선치료선량, 방사선조사야, 화학요법 병행 여부에 따라 생존률을 분석한 결과 연령 (p=0.0121), KPS(p=0.0002), 조직학적 등급(P=0.0001), 수술적 제거 (p=0.0240)가 유의한 예후인자로 분석되었으며, 통계학적으로 유의하지는 않았지만 천막하병소가 천막상부 병소에 비해, 부분조사가 전뇌조사에 비해 높은 생존률을 보이는 매개변수로 분석되었다.련된 생존율에 영향을 주었던 인자로는 나이 (p<0.0291), 병기(p<0.0001), 전신상태(p<0.0041), 초기 혈색소 수치 (p<0.0001), 강내 조사(p<0.0004)였고, 조직학적 소견(p<0.29), 유도 화학요법과의 병행치료(p<0.87)는 통계학적으로 유의하지 않았다..0093{\pm}0.0047)\;D^2+(13.31{\pm}7.309$) 였었다. 감마선에 대한 중성자선의 상대적 생물학적 효과비 (RBE)는 y=aD+$bD^2$+c를 다음과 같은 식으로 변형시켜 계산하였다. $$\frac{[-a{pm}\sqrt{a^2-4b\;(c-y}}]}{2{\times}6}$$ 미세핵 발생빈도가 세포당 0.05와 0.8사이에서의 중성자선의 상대적 생물학적 효과비는 $2.37{\pm}0.

• Maxillofacial Plastic and Reconstructive Surgery
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• 제28권3호
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• pp.193-201
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• 2006

Squamous cell carcinoma(SCC) of head and neck(SCCHN) is the sixth most common human malignant tumor. However, despite advances in prevention and treatment of SCC, the five-year survival rates for patients remain still low. To improve the outcome for patients with SCCHN, novel treatment strategies are needed. Overexpression of the epidermal growth factor(EGF) and activation of its receptor(EGFR) are associated with progressive growth of SCCHN. Vascular endothelial growth factor(VEGF) signaling molecules are related with neoangiogenesis and vascular metastasis of SCC. In this study, we determined the therapeutic effect of AEE788(Novartis Pharma AG, Basel, Switzerland), which is a dual inhibitor of EGFR/ErbB2 and VEGFR tyrosine kinases, on human oral SCC. At first, we screened the expression of EGFR, c-ErbB2(HER-2) and VEGFR-2 in a series of human oral SCC cell lines. And then we evaluated the effects of AEE788 on the phosphorylation of EGFR and VEGFR-2 in a oral SCC cell line expressing EGFR/HER-2 and VEGFR-2. We also evaluated the effects of AEE788 alone, or with paclitaxel(Taxol) on the oral SCC cell growth and apoptosis. As a result, all oral SCC cells expressed EGFR and VEGFR-2. Treatment of oral SCC cells with AEE788 led to dose-dependent inhibition of EGFR and VEGFR-2 phosphorylation, growth inhibition, and induction of apoptosis. Moreover, AEE788 sensitizes the cells to paclitaxel-mediated toxicity and apoptosis. These data mean EGFR and VEGFR-2 can be reliable targets for molecular therapy of oral SCC, and therefore warrant clinical use of EGFR/VEGFR inhibition in the treatment of patients with recurrent or metastatic oral SCC.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• 제37권1호
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• pp.15-20
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• 2011

Introduction: The characteristics of oral tongue squamous cell carcinomas (SCC) and the treatment results were reviewed to determine the appropriate treatment strategies. Materials and Methods: The medical records of 140 patients diagnosed and treated for oral tongue SCC at Yonsei University Health System from January 1995 to December 2004 were reviewed. For statistic analysis, the survival rate was determined using the Kaplan-Meier method with SPSS version 12.0, and the difference in survival rates was evaluated using a log-rank test. Results: The mean age of the patients with oral tongue SCC patients was 55 (19-85 years old). According to the T, N and pathologic stage, the patients were distributed from a higher to a lower incidence of cases, as follows: T2 (46.4%), T1 (37.9%), T4 (8.5%), and T3 (7.1%); N0 (65%), N1 (20.7%), N2 (13.6%), and N3 (0.7%); and stage I (31.4%), stage II(25.7%), stage IV (22.2%), and stage III (20.7%). Local and regional recurrence and distant metastasis was present in 13.6%, 5% and 4.2% of patients, respectively. The five-year survival rate was 72.2%, and the prognostic factors for oral tongue SCC included neck metastasis, pathologic stage of the disease, cell differentiation, treatment modality, neck dissection as part of the treatment plan, and neck node recurrence. Discussion: It is suggested that ipsilateral neck dissection or bilateral neck dissection should be selected as a treatment of tongue SCC patients with advanced stage.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• 제30권6호
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• pp.474-481
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• 2004

Squamous cell carcinoma is the most prevalent oral cancer, which is characterized by its low survival rate, high malignancy, mortality with facial defects, and poor prognosis. Exact cause and pathogenesis of the squamous cell carcinoma is still unknown. Various routes including smoking, radiation, and viral infections predispose its genesis, and recent studies revealed that genetic defects which fail to prevent cancer proliferation play a role. Generally, a cancer develops from the decreased rate of apoptosis which is an active and voluntary cell death, and from the altered cell cycles. Anticancer effect can be obtained by recovering the apoptotic process, and by suppressing the cell cycles. Among the apoptosis related factors, bcl-2, caspase-9, and VDAC (voltage-dependent anion channel)are produced in mitochondria of the cell. Cyclosporin-A is known to induce apoptosis through its activation with VDAC. This study was to reveal the anticancer effect of Cyclosporin A to the oral squamous cell carcinoma. The inverted microscope was used to find alterations in the tissue, and sensitivity test to the anticancer cells was performed with MTT (Tetrazolium-based colorimetric) assay. Following cell line culture of primary and metastastic oral squamous cell carcinoma, electrophoresis was performed with extracted total RNA. Finally, semi-quantitative study was carried out through RT-PCR (Reverse Transcription-Polymerase Chain Reaction). The results of this study are as follows: 1. The inverted microscopic observation revealed a poorly defined cytoplasm at $2000ng{\sim}3000ng/ml$, indistinct nucleus, and apoptosis. 2. The Growth of cancer cells was decreased at 1000ng/ml of cyclosporin-A. No cancer cell growth was observed at over 2000ng/ml concentration of cyclosporin-A, and at one week, growth of cancer cells was ceased. 3. The MTT assays were decreased as cyclosporin-A concentration was increased. This means that the activation of succinyl dehydrogenase in mitochondria was decreased following administration of cyclosporin A. 4. A result of RT-PCR showed that amount of mRNA of VDAC-2 was decreased half times at a cyclosporine-A concentration of 2000ng/ml. In bcl-2, amount of mRNA was significantly decreased 1/5 times at 2000ng/ml. caspase-9, however, showed slight increase compared to the control group. From the results obtained in this study, administration of cyclosporin-A to the cell lines of oral squamous cell carcinoma induced alterations in morphology and growth of the cells as its concentration increased. Since apoptosis related factors such as VDAS-2, bcl-2, and caspase-9 also showed distinct alterations on their mRNAs, further research on cyclosporin A as an anti-cancer agent will be feasible.

• Maxillofacial Plastic and Reconstructive Surgery
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• 제32권2호
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• pp.118-125
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• 2010

Background and Purpose: Bone metastases rarely occur in patients with oral squamous cell carcinoma (OSCC), so the molecular mechanisms of bone metastasis of OSCC remains unclear. Studies with animal models allow progresses in understanding the molecular events for bone metastasis and provide new targets for therapy. So we tried to establish a murine model for bone metastasis of oral squamous cell carcinoma. Materials and Methods: Human OSCC cells (KB cell line) were xenografted to nude mice via direct inoculation into the tibial marrow. Mice with tibial tumors were sacrificed once a week, until seven weeks after the injection of human tumor cells. Growth of tibial tumors were observed by histology. Expression of TGF-$\beta$ and CXCR-4 in bone OSCC (experimental) and subcutaneous tumor (control) was also evaluated by immunohistochemical staining. Results: Bone OSCC was successfully induced by intra-tibial injection of KB cells. Tumor mass was developed in the marrow tissues of tibia and finally invade the endosteum of tibia. Immunohistochemical staining showed higher expression of TGF-$\beta$ in bone tumors than in subcutaneous tumors. Conclusion: A murine model of bone metastasis of OSCC was suggested that imitated the clinical findings of distant vascular metastasis. This bone tumor model should facilitate understanding of the molecular pathogenesis of OSCC bone metastasis, and aid in the developement of treatment strategies against OSCC bone metastasis.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• 제27권2호
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• pp.142-149
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• 2001

To investigate the correlation between the clinical features and the expression of p53, PCNA, and Ki-67 of the head neck squamous cell carcinoma, immunohistochemicalstaining of p53, PCNA, and Ki-67 on the paraffin embedded tissue blocks of 116 surgically removed specimens were done. The staining intensity was divided as grade 1 to grade 3 and the results were statistically analysed. 1. The positive reation rates of cell proliferation markers (PCNA and Ki-67) were higher than that of p53. There was significant correlations of the PCNA and Ki-67 expression but there was no significant correlations between p53 and PCNA or p53 and Ki-67. 2. There were no significant correlation between the expression of p53, PCNA and Ki-67 and tumor site or tumor size. 3. There was no significant differences in the positive response according to the nodal status. The node metastasis groups revealed that higher proportion of grade 3 staining of PCNA and Ki-67 than node negative group. From the above results it is concluded that p53 and cell proliferation markers PCNA and Ki-67 might have their unique mechanism involving in the growing and progression of tumor. Overexpression of p53 does not appear to represent an independent prognostic marker in head neck squamous cell carcinoma.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• 제36권2호
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• pp.125-127
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• 2010

The coexistence of aspergillosis and squamous cell carcinoma (SCC) in the maxillary sinus was very rare. To our knowledge, this is the second report of coexistent SCC and aspergillosis in the maxillary sinus. A 58-year-old man underwent surgery for unilateral maxillary sinus infection with oroantral fistula. In the surgical specimen, SCC and aspergillosis were co-detected with routine and immunohistochemical stainings. Moreover, human papillomavirus 18 (HPV-18) was detected by polymerase chain reaction in the sinus specimen. The patient was re-operated with subtotal maxillectomy and has been followed up for two years without any evidence of recurrence or metastasis. Although it is not understood how aspergillosis could induce carcinoma formation, the chronic inflammation caused by prolonged fungal infection might be carcinogenic. Moreover, HPV-16 and -18 were another causative pathogens of SCC in the head and neck region. We recommend careful examination, including preoperative cytology, in patients with maxillary sinus fungal infections because of the potential for cancer development.

• Maxillofacial Plastic and Reconstructive Surgery
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• 제33권1호
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• pp.1-9
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• 2011

Purpose: Tumor associated angiogenesis and/or lymphangiogenesis are known to be linked by VEGFR signaling pathways. These processes are regulated by several growth factors including VEGFR-2, VEGFR-3. E7080 is an orally active inhibitor of multiple tyrosine kinases including VEGFR-2, 3. Therefore, it was proposed that E7080 may inhibit angiogenesis and lymphangiogenesis. The aim of this study was to determine the effect of E7080 in a nude mouse model of OSCC. Methods: KB cells were xenografted into the submucosal tissue of the mouth floor of athymic mice. Seven days after the xenograft, the mice were randomized into 2 groups. E7080 were administered orally to the experimental group once per day. The mice were sacrificed 3 weeks after the treatment. The tumors were examined histopathologically. Immunohistochemical assays with anti- VEGF-C, VEGFR-2, VEGFR-3, phosphorylated VEGFR-2/3 (pVEGFR-2/3), and D2-40 antibodies were then performed. Results: The transplantation of human OSCC tumor cells into the mouth floor resulted in the formation of orthotopic tumors. The experimental (E7080 treatment) group showed a slowly increased tumor volume. Moreover, immunohistochemical staining demonstrated higher levels of VEGF-C, VEGFR-2, VEGFR-3, pVEGFR-2/3 and D2-40 expression in the control group than in the experimental group. Conclusion: These results suggest that E7080 may provide therapeutic benefits in OSCC.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• 제28권3호
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• pp.182-187
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• 2002

Matrix metalloproteinase(MMP) is the proteolytic enzyme of the extracellular matrix. MMPs play a role in the invasion and metastasis of malignant tumor, but it is not known whether the expression of MMPs in squamous cell carcinoma of the tongue is related to the prognostic factors of this tumor. In this study, 32 paraffin-embedded tumor specimens were examined immunohistochemically using monoclonal antibodies of MMP-2, MMP-3, MMP-10 and MMP-13. The possible relationships between the expressions of the MMPs and TNM staging, the differentiation of tumor cells, size of tumor mass and lymph node metastasis were anlaysed statistically. The results were as follows. 1. The expression of MMP-2 increased according to TNM staging (P<0.05) and lymph node metastasis (P<0.05) and the expression of MMP-2 was not affected by the differentiation of tumor cells or tumor size. 2. The expression of MMP-3 increased with increasing tumor size (P<0.05). However it was not related to TNM staging, the differentiation of tumor cells or lymph node metastasis. 3. The expression of MMP-10 was unrelated to TNM staging, differentiation of tumor cells, lymph node metastasis or tumor size. 4. The expression of MMP-13 increased as tumor size increased (P<0.05). However it was not related to TNM staging, the differentiation of tumor cells or lymph node metastasis. We concluded that the expression patterns of MMP-2, MMP-3, and MMP-13 may play a role in the diagnosis, treatment plan and prognostic evaluation of malignant tumors of the tongue.