ANTRAL POLYP VERSUS MAXILLARY SINUSITIS

박영욱,정지훈,김윤희,이상신,김연숙,이석근,Park, Young-Wook,Chung, Ji-Hun,Kim, Yun-Hee,Lee, Sang-Shin,Kim, Yeon-Sook,Lee, Suk-Keun Korean Association of Maxillofacial Plastic and Re 2008 Maxillofacial Plastic Reconstructive Surgery Vol.30 No.5

A patient complaining of chronic dull pain in the right maxillary area showed slight haziness and small ovoid radiopacity in the right antrum, which was not extended into the choanal area in radiographic views. At operation, lots of mucoid fluid admixed myxoid soft tissues was discharged and the polypoid mucosal tissues were removed. In histological examination, the removed tissues showed a polyp by the overgrowth of dermal connective tissues exhibiting severe myxoid degeneration. Throughout the entire specimen, the inflammatory reaction was diffuse but not so remarkable to produce the mucosal thickening and necrosis. The polypoid tissues were diffusely infiltrated with neutrophiles and plasma cells, but few eosinophils, resulted in the extensive myxoid degeneration together with severe vascular degeneration. Therefore, we suggest that the antral polyp is basically different in its pathogenesis and prognosis from the common maxillary sinusitis of odontogenic origin, thus the antral polyp should be carefully diagnosed when the inflamed antral lesion is recurred and diffusely degenerative with myxoid changes.

구강암에서 림프관형성 인자의 발현에 관한 면역조직화학적 연구

박영욱,권광준,이종원,Park, Young-Wook,Kwon, Kwang-Jun,Lee, Jong-Won 대한악안면성형재건외과학회 2010 Maxillofacial Plastic Reconstructive Surgery Vol.32 No.1

Background and Purpose: Vascular endothelial growth factor (VEGF)-C and VEGF receptor (VEGFR)-3 are involved in tumor lymphangiogenesis. Oral mucosal squamous cell carcinoma (OMSCC) preferentially metastasizes to cervical lymph nodes, so we investigated the expression and distribution of VEGFR-3 signaling proteins in OMSCC. Materials and Methods: Tissue samples of 18 OMSCC, 10 oral mucosal leukoplakia, and 3 normal oral mucosa were evaluated for expression of VEGF-C, VEGF-D, and VEGFR-3 by immunohistochemical staining. The presence of lymphatic vessels was determined using D2-40 staining, by which we also measured lymphatic vessel density (LVD). Results: 72% (13/18) and 56% (10/18) of tissue samples showed VEGF-C and VEGF-D immunopositivity in tumor cells and tumor-associated endothelial cells. VEGFR-3 was also expressed in most of OMSCC, which was up-regulated when compared with normal mucosa or with leukoplakia. Furthermore, LVD was higher in OMSCC than in leukoplakia. Conclusion: Taken together, our results suggest that autocrine activation of lymphatic endothelial cell via VEGFR-3 by VEGF-C and/or VEGF-D could be involved in progression of OMSCC. Therefore, VEGF-C/VEGFR-3 signaling pathway can be a molecular target for anti-metastatic therapy in OMSCC.

구강 편평상피세포암 동위종양 모델에서 전이관련 인자의 발현

박영욱,이종원,김소희,Park, Young-Wook,Lee, Jong-Won,Kim, So-Hee 대한악안면성형재건외과학회 2008 Maxillofacial Plastic Reconstructive Surgery Vol.30 No.6

Background and Purpose : Oral squamous cell carcinoma (OSCC) is one of the most aggressive tumors of the head and neck area. OSCC is known to preferentially metastasize via lymphatic system, and resulting cervical lymph node metastasis is the most reliable of treatment failure. But the biological mechanism of the regional nodal metastasis is not clear. So, we determined metastasis-related factors in orthotopic nude mouse models of OSCC. Experimental Design : Two cell lines-KB and YD-10B cells, established from human oral mucosal squamous cell carcinoma, were xenografted into the tissue space of athymic murine mouth floor. The mice were followed for tumor development and growth, the murine tumors were examined histopathologically for local invasion or regional or distant metastasis. Finally, we performed immunohistochemical assays with antiepithelial growth factor (EGF), EGF receptor (EGFR), phosphorylated EGFR (pEGFR), and anti-vascular endothelial growth factor (VEGF), VEGF receptor (VEGFR)-2, phosphorylated VEGFR-2/3 (pVEGFR-2/3) antibodies. We also determined the microvessel density. Results : Transplantation of human OSCC tumor cells into the mouth floor successfully resulted in the formation of orthotopic tumors. KB cell line showed significantly higher tumor proliferation and higher nodal metastatic potential than YD-10B cell line. Furthermore, immunohistochemical staining demonstrated higher expression of EGFR/pEGFR, VEGF, and pVEGFR-2/3 as well as higher microvessel density in KB murine tumors than in YD-10B murine tumors. Conclusion : An orthotopic model of OSCC in athymic mice was established which copies the cervical lymph nodal metastasis of human OSCC. Our mouth floor model should facillitate the understanding of the molecular pathogenesis of cervical nodal metastasis of OSCC.

구강암 마우스모델에서 림프관형성 인자가 생존율에 미치는 영향

박영욱,조주원,Park, Young-Wook,Cho, Ju-Won 대한악안면성형재건외과학회 2013 Maxillofacial Plastic Reconstructive Surgery Vol.35 No.1

Purpose: Vascular endothelial growth factor (VEGF)-C and its tyrosine kinase receptor, VEGF receptor (VEGFR)-3 are recently known to have lymphangiogenic activities in various tumor types. In this study, we determined whether the expression of lymphangiogenic factors correlate with nodal metastasis or survival in a nude mouse model of oral squamous cell carcinoma (OSCC). Methods: Three OSCC cells (KB, SCC4, SCC9) were xenografted into the right mandibular gland of athymic nude mice. The mice were followed for tumor development and growth, and the mice were sacrificed when they had lost more than 20% of their initial body weight, or the diameter of the induced tumor exceeds 20 mm. After necropsy, the murine tumors were examined histologically and radiologically (micro-positron emission tomography computed tomography) for regional or distant metastasis. We performed immunohistochemical assays with anti-VEGF-C, VEGFR-3, CD105, and D2-40 antibodies. Immunofluorescence double staining for LYVE-1/CD31 was also performed. To quantify the VEGF-C and VEGFR-3 level in the cancer tissue, Western blotting was performed. Finally, we determined the correlation between the degree of expression of VEGF-C/VEGFR-3 and the mean survival time. Results: OSCC tumor cells into the mandibular gland of the nude mice successfully resulted in the formation of recapitulating orthotopic tumor. Tumor cells of the induced tumor did not express VEGF-C. VEGF-C/VEGFR-3 expression was mainly distributed in the endothelial cells of the stromal area. There were no correlation between the degree of expression of VEGF-C/VEGFR-3 and the mean survival time of mice injected with different OSCC cell lines. Conclusion: An recapitulating orthotopic model of OSCC in nude mice was established, which copies the cervical nodal metastasis of human OSCC. Overexpression of lymphangiogenic factors seems to have no effect on survival of hosts in this in vivo experiment.

백서에서 레이저 조사가 연조직 치유에 미치는 영향에 관한 연구

박영욱,장재현,김정환,박정민,이석근,Park, Young-Wook,Jang, Jae-Hyun,Kim, Jung-Hwan,Park, Jung-Min,Lee, Suk-Keun 대한악안면성형재건외과학회 2009 Maxillofacial Plastic Reconstructive Surgery Vol.31 No.3

Objectives: This study is aimed to compare the wound healing processes between conventional scapel wound and Er,Cr:YSGG (Erbium,Chromium, Yttrium, Scandium, Gallium, Garnet) laser wound using experimental animals. Experimental Design: Two types of wounds were made by linear and round incisions using scalpel and Er,Cr:YSGG laser, respectively, on the thigh of Sprague-Dawley rats. Sprague-Dawley rats were serially sacrified as follows: post operative 12, 24, 48 hours, and 3, 7, 14 days. The skin wounds were grossly and microscopically analyzed during the healing period. Result: The Er,Cr:YSGG laser incision showed better wound healing for the linear incision experiment than the scapel incision. Whereas the scapel incision showed better wound healing for the round incision experiment than the Er,Cr:YSGG linear incision. As the Er,Cr:YSGG laser damage in the round incision experiment could be much increased compared with the round incision by scapel. So, the round incisions by the Er,Cr:YSGG laser were resulted in the poor wound healing compared with those by the scapel. Conclusion: The Er,Cr:YSGG laser is more favorable for the fast linear incision, while the scapel is more favorable for the modified round incision.

타액선 선양낭성암종에서 상피성장인자 신호전달 단백의 발현에 관한 면역조직화학적 연구

박영욱,김정환,Park, Young-Wook,Kim, Jung-Hwan 대한악안면성형재건외과학회 2006 Maxillofacial Plastic Reconstructive Surgery Vol.28 No.6

인간 타액선 선양낭성암종 조직 18례에 대한 면역조직화학적 염색을 시행하여 종물 주변의 정상 타액선 조직과 비교, 분석하여 다음과 같은 결과를 도출하였다. 1) EGF는 타액선 도관세포와 암종 조직의 50%에서 발현 되었으며, 정상 타액선 조직과 비교하여 암종 조직에서 발현이 증가되어 있지 않았다. 2) $TGF-{\alpha}$는 타액선 도관세포와 선포세포, 그리고 거의 모든 암종 조직에서 발현되었으며, 정상 타액선 조직과 비교하여 암종 조직에서 그 발현이 유의하게 증가되었다(P<0.05). 3) EGFR은 타액선 도관세포와 대부분의 암종 조직에서 발현되었으나, 발현의 강도에서 정상 타액선 조직과 암종 조직간의 차이는 없었다. 4) pEGFR은 정상 타액선 조직에서는 발현되지 않았으며, 암종 조직의 종양세포에서 그 발현이 증가되었다(P<0.05). 5) ErbB2/HER2는 타액선 도관세포와 거의 모든 암종 조직에서 발현되었으며, 정상 타액선 조직과 비교하여 암종 조직에서 그 발현이 유의하게 증가되었다 (P<0.05). 6) 검색된 인자들 중 $TGF-{\alpha}$와 ErbB2/HER2는 관사상체형 암종 조직에서와는 달리 충실형 암종 조직에서 100% 발현되어, 충실형 선양낭성암종의 증가된 악성도에 중요한 역할을 함을 암시하였다. 7) 종물 내의 종양관련 혈관내피세포에서도 위의 인자들이 모두 발현되어 종양관련 혈관내피세포는 선양낭성암종의 증식과 전이에 중요한 역할을 함을 알 수 있었다. 8) 종양 기질 내의 면역관련 세포들에서도 역시 위의 인자들이 발현되어 이들 세포들이 종양의 증식과 생존에 영향을 미칠 것이라는 추론을 가능하게 하였다. 위의 연구결과들을 종합하면 상피성장인자 신호전달계에 관여하는 인자들 중 $TGF-{\alpha}$, pEGFR, 그리고 ErbB2/HER2가 타액선 선양낭성암종에서 과발현 되었다. 따라서 이들 인자들이 타액선 선양낭성암종의 증식과 생존, 그리고 전이 과정에서 중요한 역할을 할 것이라는 추론을 가능하게 하였다. 추후 면역조직화학적 연구의 한계와 오류를 극복할 수 있는 기법으로 이들 인자들에 대한 재검색이 필요하리라 생각된다. 또한 과연 이들 인자들이 암생물학적으로 뿐만 아니라 임상적으로도 전이 및 환자 생존율과 관계된 인자로서의 가치가 있는지 평가해 보아야 할 것이다. Malignant tumors of the human salivary glands may arise from major or minor salivary glands. Adenoid cystic carcinoma (ACC) is the second most common malignant neoplasm in the salivary glands. ACC is occasionally highly aggressive tumor that readily invades adjacent tissues and metastasize to distant organs at early stages of the disease. Although ACC tends to grow slowly, treatment outcome may be poor due to wide local infiltration, perineural or intraneural spread and a propensity for hematogenous metastasis. Therefore, knowledge of cellular and molecular characteristics that influence the growth, survival and metastasis of tumor cells, is important for new treatment strategies of salivary ACC. I determined expressions of epiderma growth factor (EGF)-signaling molecules using surgical specimens of human ACCs. Protein expressions of EGF, transforming growth $factor(TGF)-{\alpha}$, EGF receptor (EGFR), phosphorylated EGFR (pEGFR), and human EGF receptor (HER)-2 were assessed in 18 cases of salivary ACC by immunohistochemical staining. Adjacent normal salivary tissues and mucosal tissues, uninvolved by the malignant tumor, served as internal controls. Most of the tumors, especially ACC with a tubulocribriform pattern, were positive for EGF signaling molecules. The overall percentages of the 18 specimens expressing EGF, $TGF-{\alpha}$, EGFR, pEGFR, and HER2 were 50, 89, 61, 61 and 83% respectively. Moreover, tumor-associated endothelial cells and infiltrating immune-related cells in the stroma of ACC, also expressed these biomarkers. Taken together, EGF-signaling molecules are actively expressed in salivary ACC. Therefore, we suggest that these biomarkers can be molecular targets for new treatment strategies of salivary tumors.

구강 편평상피세포암에서 상피성장인자 수용체와 혈관내피성장인자 수용체 타이로신 활성화효소의 동시 억제

박영욱,이상신,Park, Young-Wook,Lee, Sang-Shin 대한악안면성형재건외과학회 2006 Maxillofacial Plastic Reconstructive Surgery Vol.28 No.3

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.

완전 구순열에서 확장 Mohler법의 적용

박영욱,Park, Young-Wook 대한악안면성형재건외과학회 2012 Maxillofacial Plastic Reconstructive Surgery Vol.34 No.3

In the repair of unilateral complete cleft lip, the most popular method is the rotation-advancement by Millard. Despite advantages of Millard repair, a few pitfalls exist. Above all, some of the scars, at the height of the cleft side philtral ridge, cross the Langer's line. Further, in the repair of complete cleft lip, small triangular lateral lip flap is often added in the base of an advancement flap to level the Cupid's bow. Moreover, preservation of the advancement flap has some negative effects on a primary nasal repair. As a result, the shape of philtrum is somewhat unnatural. Therefore, I applied the extended Mohler repair in the six cases of complete wide cleft lip to get a more esthetic scar. As a result, more natural, straight philtral ridge was obtained, without adding small triangular flap in the base of the advancement flap.

구강 편평상피세포암의 골전이 모델

박영욱,오유진,이희수,Park, Young-Wook,Oh, Yu-Jin,Lee, Hee-Su 대한악안면성형재건외과학회 2010 Maxillofacial Plastic Reconstructive Surgery Vol.32 No.2

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.

구강점막 편평상피세포암에서 림프관형성 유전자 발현

박영욱,김성곤,김소희,김한석,김민근,Park, Young-Wook,Kim, Seong-Gon,Kim, So-Hee,Kim, Han-Seok,Kim, Min-Keun 대한악안면성형재건외과학회 2009 Maxillofacial Plastic Reconstructive Surgery Vol.31 No.6

Background and Purpose: Vascular endothelial growth factor (VEGF)-C, VEGF-D and their tyrosine kinase receptor, VEGF receptor (VEGFR)-3 are recently known to have lymphangiogenic activities in various tumor types. Oral mucosal squamous cell carcinoma (OMSCC) easily metastasizes to cervical lymph nodes, so we determined the expression levels of VEGF-C, VEGF-D and VEGFR-3 in oral squamous cell carcinoma. Materials and Methods: We performed Western blot analyses with 4 OMSCC cultured tumor cell lines (SCC9, KB, YD-10B, YD-38), and with 7 surgical specimens of OMSCC for the detection of VEGF-C, VEGF-D and VEGFR-3 proteins. Expression of VEGF-C mRNA as well as mRNA for VEGFR-3 in 4 OMSCC cell lines (KB, SCC-4, SCC-9, YD-10B) was investigated by RT-PCR. We also measured VEGFC/VEGF-D protein concentrations in the media and protein concentration of VEGFR-3 in cell lysates of 4 OMSCC cell lines (SCC9, KB, YD-10B, YD-38) using commerical ELISA kits. Finally, we performed immunoprecipitation for the detection of VEGF-C in cell lysates of 4 OMSCC cells (KB, SCC-4, SCC-9, YD-10B) and real-time RT-PCR for the quantification of VEGF-C mRNA. Results: In the result of Western blotting with cell lysates of 4 OMSCC cells, we could not detect the protein expression of VEGF-C, VEGF-D, and VEGFR-3. But, all tumor tissues demonstrated VEGF-C and VEGFR-3. VEGF-C mRNA was detected at various levels in 4 OMSCC cell lines. Moreover, OMSCC cells secreted VEGF-C, not VEGF-D and VEGFR-3 was also detected in cell lysates of OMSCC by ELISA. Immunoprecipitation and real-time RT-PCR revealed VEGF-C was also expressed in 4 OMSCC cell lines. Conclusion: Taken together, tumor cells of OMSCC secrete VEGF-C, not VEGF-D. And VEGFR-3 is expressed tumor cells as well as OMSCC tumor tissues, needs further study.