위암의 침윤과 전이에 관여하는 단백분해 효소 ( uPA , PAI - 1 및 Type 4 Collagenase ) 에 관한 연구

조재용(J . Y . Cho),정현철(H . C . Chung),노성훈(S . H . Noh),김호근(H . K . Kim),박준오(J . O . Park),이종인(J . I . Lee),유내춘(N . C . Yoo),김주항(J . H . Kim),노재경(J . K . Roh),김병수(B . S . Kim),강진경(J . K . Kang),민진식(J . S 대한내과학회 1997 대한내과학회지 Vol.52 No.1

N/A Objectives : Prognosis of gastric cancer is related to invasion and metastasis. Evidence has accumulated that invasion and metastasis in solid tumors require the action of tumor associated proteases, which promote the dissolution of the surrounding tumor matrix and the basement membrane. The serine protease [(urokinase-type plasminogen activator and plasminogen activator inhibitor-1 (PAI-1)] and type IV collagenase(MMP-9 and MMP- 2) appear to play a key role in these processes. Recent reports have demonstrated that expression of these proteolytic enzymes are elevated in breast and colon cancer and that it can be associated with invasiveness and poor prognosis. We therefore evaluated whether the expression and activation of uPA, PAI-1 and type IV collagenase might be of clinical value in gastric cancer as a tumor/biologically defined risk factor. Methods: In a consecutive series of 160 gastric cancer patients who were enrolled in the Yonsei Cancer Center Study Group, the expression of uPA, PAI-1 and type IV collagenase was determined by ELISA, zymography and mmunohistochemical method. The results were as follows. Results: 1) Both uPA and PAI-1 levels were significantly higher in cancer tissues than no rmal (uPA; 9.4±8.7vs 5.3±3.1 ng/mg protein cytosol, PAI-1;10.9±9.1vs 5.8± 2.9 ng/mg protein cytosol), (p<0.001 respectively). Both high uPA and PAI-1 levels were associated with differentiation of the tumor(p=0.04, p=0.004), and a high PAI-1 level was associated with lymph nodes metastasis at an advanced stage (p=0.003, p=0.04). There was a correlation between the levels of uPA and PAI-1 expression in cancer tissues(r=0.57). 2) The activation ratio of MMP-9 and MMP-2 in cancer tissues 0.32±0.25, 0.27±0.34 were significantly higher than in normal tissue 0.19±0,27, 0.06± 0.16(p<0.001). The MMP-9 activation was associated with lymphnode metastasis and the MMP-2 activation was associated with distant metastasis(p=0.011, p=0.041). 3) In univariate analysis all of the proteolytic enzymes were associated with short relapse free survival, but in multivariate analysis only the high uPA expression was an independent prognostic parameter for short relapse free survival of the gastric cancer patients. Conclusion: These data indicate that uPA, PAI-1 and type IV collagenase were involved in the progression of gastric cancer at different points of time by different mechanisms. The combined expression and activation of these proteolytic enzymes were poor prognostic factors in gastric cancer patients, so new therapy based on these biologic behavior of the tumor in the same stage are clinically applicable. In particular, uPA is a new independent variable for the identification of patients at high risk, therefore therapy targetting uPA can be applied as a new treatment modality for gastric cancer.

국소진행성 직장암에서 수술 전 방사선 및 항암화학 동시요법의 효과

조재호(J ae Ho Cho),성진실(Jinsil Seong),금기창(Ki Chang Keum),김귀언(Gwi Eon Kim),서창옥(Chang Ok Suh),노재경(Jae Kyung Roh),정현철(Hyun Cheol Chung),민진식(Jin Sik Min),김남규(Nam Kyu Kim) 대한방사선종양학회 2000 Radiation Oncology Journal Vol.18 No.4

목 적 : 직장암에서 완치를 기대할 수 있는 치료는 수술요법이다. 진행성 병변으로서 근치절제가 불가능한 경우에 있어서는 수술 전 보조요법을 통해 절제연이 음성인 근치절제율을 높이고자 하는 노력이 시도되고 있다. 이에 저자들은 수술 전 방사선 및 항암화학 동시요법으로 근치 절제율을 높여 치료성적을 향상시키기 위하여 전향적 임상 연구를 시행하였다. 대상 및 방법 : 1995년 1월부터 1998년 6월까지 국소적으로 진행된 직장암으로 내원하여 수술전 병기결정 검사를 통하여 근치적 절제가 불가능하다고 판단된 37명의 환자가 본 연구에 포함되었다. 수술전 병기결정은 직장수지검사, 경직장초음파, 컴퓨터단층촬영, 자기공명영상 등을 이용하였다. 방사선 치료는 3 문 내지 4 문 조사식으로 총 45∼50.4 Gy를 시행하였으며, 방사선 치료 첫째 주와 다섯째 주에 항암 화학요법(5- Fluorouracil, 370∼450 mg/m2 , IV bolus, 5 days; Leucovorin 20 mg/m2 , IV bolus, 5 days)이 동시에 투여되었다. 방사선 치료 후 4∼6주 후에 근치적절제술을 시행하였다. 전체 37명의 환자 중 31명에서 계획된 방사선 및 항암화학 동시요법 후 근치적 수술이 시행되었고, 나머지 6명은 환자 이해부족으로 치료가 중단 된 경우 4예, 치료중 진행성 병변(Perforation)으로 응급수술을 시행한 후 방사선 단독치료를 한 경우 1예, 그리고 1예에서는 방사선 및 항암화학 동시요법을 시행 후 수술하기 전에 폐전이가 발견되어 전신항암화학 요법만을 시행하였다. 결 과 : 계획된 치료가 시행된 환자 중 94% (29/31)에서 절제연 음성인 완전근치절제가 가능하였으며, 병리적 완전관해율은 6% (2/31), 임상적 완전관해율은 23% (7/31)이었다. 수술 전 병기 감소율은 68%에서 관찰되었다. 수술은 2예에서 국소 절제술, 14예에서 저위전방절제술, 8예에서 복회음부 절제술, 4예에서 하트만씨 절제술, 3예에서 부분 내용제거술을 시행되었다. 치료와 연관된 급성 독성으로는 Grade III & IV의 백혈구 감소증 각각 4예(13%), 2예(6%)를 제외하고는 대부분 경미하였다. 결 론 : 국소적으로 진행되어 근치적 절제가 어려운 직장암에서 계획된 수술 전 방사선 및 항암화학 동시요법을 통해서 수술 후 병기 감소(68%)와 높은 완전근치절제율(94%)을 얻을 수 있었다. 치료에 따른 독성도 대부분 경미하여 좋은 순응도를 보였다. 나아가 이러한 치료를 통해 얻어지는 국소 제어율과 전체 생존율에 대해서는 향후 추적 관찰을 통해 분석해 나갈 예정이다. Purpose :We conducted a prospective non- randomized clinical study to evaluate the efficacy and toxicity of the preoperative concurrent chemoradiotherapy for locally advanced unresectable rectal cancer. Materials and Methods : Between January 1995 and June 1998, 37 consecutive patients with locally unresectable advanced rectal cancer were entered into the study. With 3- or 4- fields techniuqe, a total of 45 Gy radiation was delivered on whole pelvis, followed by 5.4 Gy boost to the primary tumor in some cases. Chemotherapy was done at the first and fifth week of radiation with bolus i.v. 5- Fluorouracil (FU) 370∼450 mg/m2 , days 1∼5, plus Leucovorin 20 mg/m2 , days 1∼5. Of 37 patients, 6 patients did not receive all planned treatment course (refusal in 4, disease progression in 1, metastasis to lung in 1). Surgical resection was undergone 4∼6 weeks after preoperative concurrent chemoradiotherapy. Results :Complete resection rate with negative margins was 94% (29/31). Complete response was seen in 7 patients (23%) clinically and 2 patients (6%) pathologically. Down staging of tumor occured in 21 patients (68%). Treatment related toxicity was minimal except grade III & IV leukopenia in 2 patients, respectively. Conclusion : Preoperative concurrent chemoradiotherapy in locally advanced rectal cancer was effective in inducing down staging and complete resection rate. Treatment related toxicity was minimal. Further follow up is on- going to determine long term survival following this treatment.

비소세포폐암에서 p53유전자의 구조적 이상 및 단백질 발현이 예후에 미치는 영향

이이형 ( Y. H. Lee ),신동환 ( D. H. Shin ),김주항 ( J. H. Kim ),임호영 ( H. Y. Lim ),정경영 ( K. Y. Chung ),양우익 ( W. I. Yang ),김세규 ( S. K. Kim ),장준 ( J. Chang ),노재경 ( J. K. Roh ),김성규 ( S. K. Kim ),이원영 ( W. Y. Lee ) 대한결핵 및 호흡기학회 1994 Tuberculosis and Respiratory Diseases Vol.41 No.4

다발성 원발성 악성종양

권혁문(Hyuck Moon Kwon),정재복(Jae Bock Chung),김주항(Joo Hang Kim),전상일(Sang Il Chun),조준구(Jun Koo Cho),박용준(Yong Jun Park),고은희(Eun Hee Koh),노재경(Jae Kyung Roh),서창옥(Chang Ok Suh),김귀언(Gwi Eon Kim),노준규(J . K . Loh) 대한내과학회 1987 대한내과학회지 Vol.33 No.1

N/A There is no acceptable evidence, either in this presentation of in the literature, that the patterns of occurance of multiple primary maligant neoplasms of different organs of tissues are governed by anything more than conincidence. The freqency of occurance of specific types of second primary cancers is probably largely determined by the age of the patient at the time of diagnosis of initial cancer and the expected longevity after treatment of the initial lesion. The absolute number of reported cases of multiple primary malignant tumors has increased in recent years and the freqency of occurance of this phenomenon has increased. There is no factual basis for assuming that the existence of any one malignant neoplasm influence or that it implies any susceptibility of any other organ or organ system to future cancer. But it becomes apparent that existence of one malignant neoplasm implies increased susceptibility to the development of a second lesion but also a malignant lesion in one organ may imply increased susceptibility of another organ to malignant neoplasm, particularly another organ in the same or an associated system. This report deals with the clincal analysis of 42 cases of multiple primary malignant tumors from tumor registry of Severance hospital and yonsei cancer center during 7 years from Jan 1979 to Dec. 1985 and review of the literatures, The following results were abtained. 1) The incidence of multiple primary malignant tumor was 0.26% of tumor registry (42/25, 863) and the mean age of 26 male patients at first cancer was 58.8 years old and 54.9 years old in 16 female patients. 2) The mean time interval between first and second cancer was 34.1 months in 12 metachronous tumors. 3) In male patients, the stomach cancer was the most common first cancer followed by lung cancer. In female patients, the cancer of uterine cervix was the most common first cancer. 4) The ratio between synchronous and metachronous multiple primary was 2.5:1 (30:12).