흉선종의 세포학적 검색

공구,장세진,이중달,Kong, Gu,Jang, Se-Jin,Lee, Jung-Dal 대한세포병리학회 1990 대한세포병리학회지 Vol.1 No.1

The fluoroscopy-guided fine needle aspiration biopsy has been gaining widespread acceptance as a rapid and effective method to make a pre-operative diagnosis of mediastinal tumors including thymoma, malignant lymphoma, and metastatic carcinoma. Although thymoma is a most common tumor of the superior mediastinum, most cytopathologists are not experted in cytologic diagnosis of this tumor because of limited experience. In order to define the diagnostic cytologic features of thymoma, we have retrospectively reviewed imprinting smears and corresponding tissue sections from four cases of this tumor. All cases revealed an apparent biphasic pattern of epithelial cell clusters and lymphocytes with occasional branching capillary fronds extending from three dimensional epithelial cell clusters. Epithelial cell clusters predominated in one case and lymphocytes in two cases. Mixed epithelial cell and lymphocyte type represented in one of four cases. In the lymphocyte predominant type, the presence of epithelial cell clusters and small mature lymphocytes are helpful features to differentiate from a malignant lymphoma.

흉선 유암종의 세침 천자 세포학적 소견 - 1 예 보고-

공구,이중달,Kong, Gu,Lee, Jung-Dal 대한세포병리학회 1991 대한세포병리학회지 Vol.2 No.2

Diagnosis of a thymic carcinoid was made on transthoracic fine needle aspiration in a 36-year old woman who had an anterior mediastinal mass on chest X-ray and CT scan. The aspiration smears showed numerous anastomosing ribbons and cords of small round tumor cells. The tumor cells had slightly eccentric nuclei and some granular cytoplasm. The small and uniform nuclei of the tumor cells had finely granular chromatin and thin nuclear membrane. The cytologic diagnosis of a carcinoid was confirmed on histopathologic, immunohistochemical, and electromicroscopic examination of surgical specimen.

Cytologic Features of Endometrial Papillary Serous Carcinoma

공구,홍은경,이중달,Kong, Gu,Hong, Eun-Kyung,Lee, Jung-Dal The Korean Society for Cytopathology 1990 대한세포병리학회지 Vol.1 No.2

자궁내막의 유두상 장액성 암종은 자궁 내막에서 발생하는 매우 희귀한 선암종의 한 형태로, 동명의 난소 암종과 조직학적으로 동일하며, 매우 불량한 예후를 나타낸다. 대개 이 종양은 말기에 진단되며, 같은 조직학적 소견을 보이는 전이성 난소암종과 혼돈되기 쉽다. 최근, 저자들은 자궁경부-질 도말 표본에서 2예의 유두상 장액성 암종을 진단 하였는데, 그 세포학적 소견은 종양 세포의 유두상 구조가 풍부하게 도말되었고, 종양 세포들은 거대한 핵소체를 가지고 있었다. 도말배경은 괴사성 및 혈성으로 종양소인을 잘 반영하고 있었다. 이 세포학적 진단은 자궁 절제 표본의 조직학적 검사로 확인 되었다. Endometrial papillary serous carcinoma (EPSC) is a distinct variant of endometrial adenocarcinoma that histologically resembles ovarian serous papillary adenocarcinoma and has an aggressive clinical course. Usually, the tumor is diagnosed at the advanced stage. The tumor has well confused with metastatic ovarian tumor of identical histology. Dignosis of EPSC should be considered when the cervico-vaginal smear reveals nomerous papillary clusters of tumor cells with macronucleoli and psammoma bodies. Recently, we have experienced two cases of EPSC diagnosed on cervico-vaginal smears, which revealed characteristic cytologic features including numerous papillary clusters of tumor cells with macronucleoli. The cytologic diagnoses were confirmed on histologic sections.

자궁 경부의 유리질 세포 암종의 세포학적 소견

공구,김은경,홍은경,이중달,Kong, Gu,Kim, Eun-Kyung,Hong, Eun-Kyung,Lee, Jung-Dal 대한세포병리학회 1991 대한세포병리학회지 Vol.2 No.1

Glassy cell carcinoma is an unusual neoplasm of the uterine cervix with highly aggressive clinical behavior. On cervico-vaginal smear examination, the tumor has well confused of atypical repair ceil of the endocervix. Recently, we have experienced two cases of glassy cell carcinoma of the uterine cervix, diagnosed on cervico-vaginal smears and confirmed on fellowing histologic sections. The cervico-vaginal smears revealed abundant clusters with well defined boarders. The cell clusters were composed of large tumor cells. The tumor cells had distinct granular cytoplasm and eosinophilic macronucleoli, Characteristic cytologic features of this tumor were discussed in view of differential diagnosis.

쥐모델에서의 이소성의 심장이식

정원상,전양빈,전순호,김혁,이철범,김영학,지행옥,서정국,공구,Chung, Won-Sang,Jeon, Yang-Bin,Chun, Soon-Ho,Kim, Hyuk,Lee, Chul-Burm,Kim, Young-Hak,Jee, Heng-Ok,Seo, Jung-Kuk,Kong, Gu 대한흉부심장혈관외과학회 1998 Journal of Chest Surgery (J Chest Surg) Vol.31 No.5

국내에서 심장, 폐이식이 각 대학병원에서 점차 확산 시행되고는 있으나, 이에 따른 기초실험이 뒷받침되지 않고, 큰 동물에서는 많은 실험비용이 들어 보다 적은 동물을 이용하게 되었으나 이 방법은 현미경하의 미세수술기법의 발달과 더불어 발전하게 되었다. 본 연구는 현미경하의 미세수술기법으로 쥐모델에서 복부의 대동맥과 하공정맥에 다른 쥐의 공여심장의 대동맥과 폐동맥을 각각 문합술로 연결하는 방법으로 이식하여 동종이형의 장기이식에 따른 거부반응과 면역억제제를 투여하여 그에 따른 생존율을 비교하고자 하였다. 체중 150∼250 gm의 흰쥐의 심장을 공여 및 이식하는 바, 이소성의 심장이식후 면역억제제를 투여하지 않은 군과 면역억제제를 투여한 군으로 나누고, 각 군에서 복부에 이식된 심장의 박동을 매일 만져보고서 만져지지 않을 경우는 이식된 심장이 거부반응에 따른 것으로 판단하여 이의 생존율을 비교 검토하여본 바, 면역억제제를 투여하지 않은 군에서보다 투여한 군에서 오래 생존하여 동종이형의 이식에서 면역억제제를 투여하므로써 장기이식에 따른 장기성적을 향상시킴을 알 수 있었다. In 1964, Abbott and Colleagues published the world's first heterotopic heart transplantation technique in the rat. Their method established circulation by end-to-end anastomoses of the graft's aorta and pulmonary artery to the recipient's abdominal aorta and Inferior Vena Cava(IVC), respectively. In 1966, Tomita et al altered Abbott's technique by employing end-to-side rather than end-to-end anastomoses, thus eliminating the hind leg paralysis that sometimes resulted from Abbott's technique. In order to prevent postsuture hemorrhage (since 7-0 silk suture was the finest available at that time), Tomita's aortic anastomosis was done with double up-and-down continuous suture technique. A single layer continuous anstomosis effected the pulmonary artery-IVC anastomosis. The availability of Nylon monofilament suture made it possible for Ono and Lindsey to use a single layer suture technique for the aortic end-to-side anastomosis in their modified rat heart transplantation. We observed survival time between control group and Immunosuppression(Cyclosporine administration, 10mg/Kg${\times}$4 times postoperatively) group after heterotopic heart transplantation in the rat model. The cyclosporine adminstration group survived longer than the control group, thus we concluded that cyclosporine was based on Immunosuppressive drugs.

인체 유방암 세포에서 retinoids의 영향에 대한 연구

윤현정(Hyun Jung Yoon),신윤용(Yhun Yhong Sheen),공구(Gu Kong) 한국환경성돌연변이발암원학회 2004 한국환경성돌연변이·발암원학회지 Vol.24 No.2

Retinoids, better known as vitamin A, have been reported to inhibit the growth of several breast cancer cell lines in culture and to reduce breast tumor growth in animal models. Furthermore, retinoids can augment the action of other breast cancer cell growth inhibitors both in vitro and in vivo. Clinically, interest has increased in the potential use of retinoids for the prevention and treatment of human breast cancer. We have examine the effect of all-trans retinoic acid(tRA) and 9-cis retinoic acid(9-cis RA) on human breast cancer cell(MCF-10A, T47-D, MCF-7) proliferation using MTT assay and cell cycle analysis(FACS), Overexpression of cyclin D1 protein is observed in the majority of breast cancers, suggesting that dysregulated expression of cyclin D1 might be a critical event in breast cancer carcinogenesis. We investigated whether tRA and 9-cis RA might affect expression of cyclin D1 on human breast cancer cells(MCF-10A, T47-D, MCF-7) using RT-PCR and western bolt. In MCF-IOA cells, either tRA or 9-cis RA treatment did not affect the cell proliferation. In T47-D cells and MCF-7 cells, either tRA or 9-cis RA treatment showed the inhibition of the cell proliferation over control cells and also inhibit the estrogen stimulated cell proliferation when it was given together with estrogen. The effect of retinoids was dose-and time-dependent. T47-D cells treated with 1.0 μM tRA undergo G0/G1-phase arrest by Day 5. MCF-7 cells treated with 1.0 μM tRA undergo S-phase arrest by Day 5. All-trans retinoic acid(tRA) and 9-cis retinoic acid(9-cis RA) inhibited the cyclin D1 mRNA and protein expression levels of human MCF-7 and T47-D breast carcinoma cells in vitro. The data indicate that retinoids can reduce cyclin D1 expression levels in a variety of breast cell lines in vitro and result in inhibition of cell proliferation. tRA-mediated growth inhibition and cyclin D1 expression inhibition is more potent than 9-cis RA mediated that. tRA-mediated inhibition effect is more Potent on T47-D cells than on MCF-7 cells. Our data suggest that retinoids activity is different according to property of cell lines. Future chemoprevention of breast cancer studies using retinoids will be necessary to determine the mechanism of the retinoids-mediated growth inhibition.

인체 유방암 세포에서 과다발현 시킨 Cyclin D2의 영향에 대한 연구

김현준(Hyun Jun Kim),이근수(Geun Soo Lee),전상학(Sang Hak Jeon),공구(Gu Kong) 한국환경성돌연변이발암원학회 2004 한국환경성돌연변이·발암원학회지 Vol.24 No.1

Three D-type cyclins (D1, D2, and D3) are expressed in G1 phase of the cell cycle and have been implicated in cell transformation and neoplasia in human and mouse. Cyclin D1 overexpression or amplification was described in various human cancers. However, there is controversy about the role of cyclin D2 in cell cycle progression and human carcinogenesis. Specially, loss of cyclin D2 is involved in a vital tumor suppressor function in normal breast tissue, and that its loss may be related to tumorigenesis. The author examined to effect over-expression of cyclin D2 on the cell proliferation, apoptosis, and cell cycle using cyclin D2 transfected stable T47D breast cancer cells to investigate whether cyclinD2 functions as a positive regulator or negative regulator in cell proliferation. Overexpression of cyclin D2 led to the suppression of cell growth in cyclin D2 transfected T47D in both in its expression level and a time dependent manner with up to 50% reduction of cell growth at 72 hours. Therefore, the authors performed the cell cycle phase analysis using the flow cytometry to investigate the effect of cyclin D2 on the cell cycle phase in cyclin D2 transfected stable T47D cells. The flow cytometry analysis revealed increased sub G0 phase in cyclin D2 transfeted cells up to 23% at 72 hours. To confirm these results induced by overexpression of cyclinD2, the apoptotic bodies were counted in control and cyclin D2 transfected T47 cells. There are markedly increases of apoptotic bodies in cyclin D2-transfected cells up to 18%. These results suggested that Cyclin D2 suppresses the cell proliferation in breast cancers cells via the induction of apotosis.

한국인 두경부암 환자에서 CYP1A1 및 GSTM1 유전자 다형성 분석에 의한 유전적 감수성에 대한 연구

김현준(Hyun Jun Kim),채현기(Hyun Ki Chae),태경(Kyung Tae),공구(Gu Kong) 한국환경성돌연변이발암원학회 2000 한국환경성돌연변이·발암원학회지 Vol.20 No.1

Genetic polymorphisms of metabolizing enzymes to chemical carcinogens have been recognized as a major important host factors in human cancers. To determine the frequencies of genotypes of CYP1A1 and GSTM1 metabolizing enzymes in healthy controls and head and neck cancer patients in Korean and to identify the relative high risk genotypes of these metabolizing enzymes to head and neck cancer, we have analyzed 133 head and neck cancer patients and corresponding healthy controls matched in age and sex using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). In analysis of CYP1A1, the Val/Val genotype of exon 7 polymorphism and m2/m2 genotype of Msp 1 polymorphism were associated with higher relative risks to head and neck cancers (Odds ratio : 2.34, 95% CI : 0.79-6.96 and 1.27, 95% CI : 0.59-2.73,<br/> respectively). In combined genotyping of CYP1A1 and GSTM1 enzymes polymorphisms, the patients with Val/Val and GSTM1(-), and m1/m2l and GSTM1(-) combined genotypes had higher relative risks than the patients with each base genotype of combined genotypes (Odds ratio : 4.57, 95% CI : 0.51-41.25 and 1.65, 95% CI : 0.73-3.77, respectively). These results suggest the combined genotype of Val/Val and GSTM1(-) was more susceptible to head and neck cancers in Korean and genotyping of metabolizing enzymes could be useful for predicting individual genetic susceptibility and screening the high risk subpopulation to head and neck cancer in Korean.

배양한 인체의 혈관간세포(Mesangial Cells)에서 활성화 산소종(Reactive Oxygen Species)의 발생과 이에 관련한 세포외 기질 증가에 있어서 Cyclosporine과 Tacrolimus의 차이점

이승구(Soong Ku Lee),이수진(Su Jeen Lee),김현준(Hyun Jun Kim),공구(Gu Kong),강경원(Kyoung Won Kahng),강종명(Chong Myung Kang) 대한신장학회 2001 Kidney Research and Clinical Practice Vol.20 No.2

신장이식에 사용하는 중요한 면역억제의 하나인 cyclosporine(CsA)과 tacrolimus(FK506)의 물질 구조는 완전히 다르나 면역억제의 기전은 유사하며 면역억제 효과는 tacrolimus가 CsA에 비해 더 강하다. 이 두 약제는 신장의 섬유모세포에서 collagen 발현의 정도, 혈관간세포(mesangial cell) 배양시 matrix metalloproteinases(MMPs)와 tissue inhibitors of matrix metalloproteinases(TIMPs)의 변화 등에서 차이가 있다고 보고된다. 한편 CsA은 배양세포에서 활성과 산소종(reactive oxygen species;ROS)을 발생시키며, 발생된 ROS는 세포외 기질의 축적에 영향을 미친다고 한다. 따라사ㅓ 저자들은 tacrolimus와 CsA가 ROS의 발생하는데 차이가 있는지 조사하고 이와 같은 차이가 세포외 기질의 축적에 어떤 영향을 미치는지 조사하고자 본 연구를 시행하였다. 방법 : 4대에서 8대 사이의 계대배양한 인간의 혈관간세포에 CsA을 각각 다른 농도(0, 2, 4, 8μg/mL)로 투여하였고, 또 다른 4μg/mL의 농도로 CsA를 투여한 세포군에 항산화제인 N-acetylcysteine(NAC)을 같이 투여하였다. Tacrolimus도 같은 방식으로 투여하였는데, 농도는 0, 0.1, 0.2, 0.4μg/mL으로 하였으며 NAC는 또 다른 0.2μg/mL의 dish에 투여하였다. 결과 : 실험한 세포들에서 생존율은 변화가 없었으나 CsA 투여군에서 tacrolimus 투여군에 비해 유의하게 세포 증식의 차이가 있었다. Flow cytometry에서 CsA 투여군은ROS의 생성을 확인할 수 있었으나 tacrolimus군은 확인할 수 없었고, CsA 군은 세포의 증식이 농도에 따라 감소하다가 다시 NAC에 의해 회복되는 것을 확인할 수 있었다. MMP2, TIMP2, MT1-MMP, Collagen III에 대한 RT-PCR 결과는 두 군 모두 변화가 없었으나 zymogram상에서 CsA 군은 MMP2의 활성도가 농도가 증가함에 따라 감소하였고 이는 다시 NAC에 의해 일부 회복되었으나 tacrolimus군은 이와 같은 변화가 없었다. 결론 : 저자들의 실험에서는 배양한 인체의 혈관간세포에서 일정 시간에서 CsA 투여에 따라 ROS가 발생함을 확인하였으나 tacrolimus에서는 ROS의 발생을 관찰하지 못하였다. CsA는 기질분해 효소인 MMP2의 활성도를 post-transcriptional level에서 tacrolimus에 비해 현저하게 감소시켰으며 이는 CsA에 의해 발생한 ROS와 연관되어 있었다. 하지만 tacrolimus도 더 높은 농도 (0.4μg/mL)에서는 MMP2의 활성도는 전사 후 과정 (post-transcriptional level)에서 감소시켰다. 따라서 tacrolimus와 CsA이 신독성이 유사한 점을 고려하면, 두 약제가 혈관간세포에 영향을 주는 작용기전은 서로 동일하지 않은 것으로 생각되며 이에 대한 더 많은 in Vitro 및 Objective: Cyclosporine(CsA) and tacrolimus, albeit different in structure, exert immunosuppressive effect by similar mechanism. Although most of clinical manifestations, including nephrotoxicity, are simi- lar in the patients using these drugs, there are some differences including gum hyperplasia, neurotoxicity, and hepatic fibrosis between two drugs. There are several reports about association between reactive oxygen species(ROS) and CsA. In contrast, tacrolimus is known to decrease ROS in central nervous system. Thus, we investigated the possibility of different effects of tacrolimus and CsA on the genera- tion of ROS, on the synthesis and degradation of collagen. Methods: Experiments were done in primary cultured mesangial cells between 4th and 8th passages. CsA was added to the culture dishes in different concentration(making final CsA concentration of 0, 2, 4, 8 μg/mL) and N-acetylcysteine(NAC) was also added in another mesangial cell culture at 4 μg/mL of CsA concentration; tacrolimus was added in similar pattern(making final tacrolimus concentration of 0, 0.1, 0.2, 0.4μg/mL, NAC in 0.2μg/mL of tacrolimus concentration). Results: No significant decrease in viability was noted in both cell groups, but growth retardation was weak in tacrolimus treated cells comparing with CsA treated cells. By flow cytometry, we could find the generation of ROS in CsA treated cells, but not in tacrolimus treated cells. In RT-PCR, there is no significant difference in m-RNA expression for a number of molecules including collagen III, MMP-2, TIMP-2, MT1-MMP in either CsA treated cells or tacrolimus cells. But in zymogram, MMP-2 activities were decreased at higher CsA concentration, then increased with addition of NAC. In tacrolimus cells, MMP2 activity was not changed at 0.1 and 0.2 μg/mL; but, at the concentration of 0.4 μg/mL, changed and not reversed by NAC. MMP-9 activity was similar in both cells. Conclusion: We could find ROS generation in CsA treated human mesangial cells, but not in tacrolimus treated cells. We think this difference resulted in the decrease of post-transcriptional MMP-2 activity in CsA treated cells and we also think tacrolimus cells in our experiments were not influenced by ROS. From these results, tacrolimus and CsA are different in the generation of ROS that have some effects in the matrix accumulation in mesangial cells. These result does not mean that tacrolimus is superior to CsA in nephrotoxicity, because nephrotoxicity is similar between two drugs. In conclusion, the mechanisms of nephrotoxicity are different between CsA and tacrolimus.

Estrogen 대사 효소의 유전자 다형성과 한국인 유방암 환자의 유전적 감수성에 대한 연구

김현준(Hyun Jun Kim),이수진(Soo-jin Lee),공구(Gu Kong) 한국환경성돌연변이발암원학회 2003 한국환경성돌연변이·발암원학회지 Vol.23 No.1

To determine the frequencies of the genotypes of estrogen metabolising enzyme (CYP17, CYP1A1, CYP1B1, and COMT) and to identify the high-risk genotypes of these metabolic enzymes to breast cancer in Korean, the author has analysed 115 breast cancer patients and corresponding age and sex matched heathy controls using polymerase chain reaction-restiction fragment length polymorphism (PCR-RFLP). A2/A2 genotype in CYP17 polymorphism, m2/m2 genotype in CYP1A1 polymorphism, and Val/Val genotype in CYP1B1 had 0.95, 1.40 and 0.76 relive risks to breast cancer comparing with reference genotypes of each polymorphism, respectively.<br/> Among the genotypes of COMT enzyme polymorphism, L/H and L/L genotypes had 0.97 and 1.54 relative risks to breast cancer, respectively. According to the number of high risk genotype, the patients with one or two putative high risk genotypes had 0.95 and 1.94 relative risks to breast cancer, respectively. This study have demonstrated the unique frequency of genotypes of estrogen metabolizing enzyme in Korean healthy women, which will provide the basic data and insights to study the estrogen related conditions in Korean women including breast and endometrial cancers. And it also indicates that the well-known high risk genotypes of estrogen<br/> metabolizing enzymes are not significantly associated with the development of breast cancer in Korean women.