Application of Gabexate Mesylate IC against MMP - 9 Using ex vivo Model in Gastric Cancer: Prognostic Factor and Selection Criteria for Anti - MMP Treatment / 대한암학회지

PURPOSE: Among the many biological characteristics of cancer, matrix metalloproteinases(MMPs) are essential for tumor invasion and metastasis. The correction of the imbalance between MMPs and tissue inhibitors of matrix metalloproteinase (TIMP) has been suggested as a possible goal for the control of invasive phenotype of the cancer. To test the possible inhibition of MMP-9 in ex vivo model and the selection of the patients who are sensitive to MMP inhibitory (MMPI) treatment, we evaluated IC50 of the gabexate mesylate (Foy) against MMP-9 and compared them to the clinical parameters and patients survivals. MATERIALS AND METHODS: Thirty-four paired normal and gastric cancer tissues were tested for the IC50 of the gabexate mesylate. MMP-9 activity was measured by zymography. RESULTS: MMP-9 expression (percent of sample band density to control band) (p=0.04) and IC50 (p=0.02) of cancer tissues were significantly higher than those of normal tissues. Cancer tissue IC50 was higher than that of normal tissues in cases when the tumor mass diameter was longer than 5 cm (p=0.03) as well as in higher T-stage (p=0.04), lymph node metastasis (p=0.04) and in advanced stages (p=0.04). There was a tendency of increased IC50 of diffuse and mixed type than that of intestinal type (diffuse & mixed: 11.0+-20.8 mg/ml, intestinal: 2.7+-3.9 mg/ml; p 0.07), in spite of no difference in MMP-9 expression (diffuse & mixed: 40.3+49.2%, intestinal: 51.0+-58.0%). In early gastric cancer (EGC), there was no difference in IC50 between normal and cancer tissues whereas cancer tissue IC50 was higher than that of normal tissue in advanced gastric cancer (p 0.02). There was a tendency of increment of ICo in cancer tissues of advanced gastric cancer than that of EGC whereas no difference was found in MMP-9 expression between these types of cancers. Poor prognosis was found in high IC50 patients in curatively resected patients (p=0.04). In multivariate analysis, high IC50 was suggested as a possible independent prognostic factor. CONCLUSION: We could differentiate the high risk patients using IC50 of gabexate mesylate in ex vivo model. This model can be applied in detecting patients with poor prognosis and patients who can have a possible benefit with MMPI treatment.

Clinical Significance of Urokinase - type Plasminogen Activator Receptor ( uPAR ) Expression in Breast Cancer Tissues / 대한암학회지

PURPOSE: Cancer invasion is induced by several proteolytic enzyme systems associated with the destruction of basement membrane and extracellular matrix. Urokinase-type plasminogen activator (uPA) and plasminogen activator inhibitor-1 (PAI-1) have been reported as prognostic factors in breast cancer patients and plasminogen activation is regulated by various factor such as uPAR and growth factor. So we examined the tissue levels of urokinase-type plasminogen activator receptor (uPAR) in breast cancer patients. MATERIALS AND METHODS: Tissue uPAR levels were measured by ELISA assay in 268 breast cancer patients. RESULTS: The median and mean values of tissue uPAR level in breast cancer were 3.5 ng/mg and 4.8+-3.6 ng/mg cytosol protein, respectively. Tissue uPAR level was the highest in T1 stage, but there was no statistical significance between T stage (p >0.05). In nodal stage, there was also no difference in the value of uPAR according to progression. And the value of uPAR expression was not associated with estrogen and progesteron receptor status, number of involved node and percent of node involvement. In TNM stage, tissue uPAR levels were higher in patients with stage I-II than in patients with stage III-IV (p=0.027). In univariate analysis, nodal factor (p=0.0023) and TNM stage (p=0.0004) were significantly associated with overall survival. But, multivariate analysis showed that TNM stage was the only significant prognostic factor (p=0.0002). CONCLUSION: These results suggest that uPAR is mainly associated with initial tumor invasion and other factors might be involved in later stages of cancer progression.

Effect of 5 - FU plus leucovorin for adjuvant chemotherapy according to dose related factors in colon cancer / 대한내과학회지

BACKGROUND: In patients with stage C colon cancer, surgery followed by adjuvant chemotherapy with 5-fluorouracil (5-FU)/leucovorin (LV) is considered to be the standard treatment. However, the objects of adjuvant therapy and the duration of treatment are still matters of controversy. We investigated the effect of dose related factor(delivered total dose of 5-FU per body square meter, actual dose intensity and relative dose intensity) of the adjuvant 5-FU/leucovorin regimen on survival in coloncancer. METHODS: Of the colon cancer patients with Duke's B2 and C stage diseases treated with curative resection from December, 1990 to December, 1996, 139 patients treated with 5-FU/LV as an adjuvant chemotherapy were evaluated. The delivered total dose of 5-FU per body square meter, actual dose intensity and relative dose intensity were obtained. The patients were divided into two groups according to the median value of each factor and the survival rates were compared. RESULTS: The total dose of 5-FU administrated per body square meter had a significant effect on the 5-year disease free and overall survival in stage B2 and C colon cancer patients(B2; p=0.025, p=0.045, respectively, C; p=0.011, p=0.0002, respectively). But survival was not affected by the dose intensity. Multivariate analysis demonstrated that only the total dose of 5-FU administrated per body surface area affected the 5-year disease free and overall survival(p=0.0016, p=0.0007, respectively). CONCLUSION: It can be concluded that the total dose of 5-FU administered is more important than the DI in adjuvant chemotherapy of colon cancer and the total dose of 5-FU had a significant effect on the survival rate in colon cancer patients. To confirm the total dose effect of 5-FU on survival in this study, multi-institutional, prospective randomized studies should be carried out.

The Efficacy and Safety of Docetaxel in Patients with Anthracychne pretreated Metastatic Breast Cancer: A Multicenter Phase II Study / 대한암학회지

PURPOSE: Tbis phase II study was performed to evaluate the efficacy and safety of docetaxel in patients with anthracycline-pretreated metastatic breast cancer (MBC). MATERIALS AND METHODS: From September 1996 to January 1998, 27 patients with metastatic breast cancer from 31 to 63 years of age with a performance status of 0 to 2 were registered in the phase II trial. All patients had metastatic breast cancer which had progressed or relapsed 2 during or after treatment with an anthracycline-based regimen. Docetaxel 75 mg/m2 was ad- ministered over 1 hour every 21 days until disease progression was documented or until toxic effects precluded further therapy. All patients received dexamethasone orally at the dose of 16 mg on days -1, 0, 1 of each cycle. RESULTS: Objective responses were seen in 9 of 25 assessable patients (two complete and seven partial responses), with an overall objective response rale of 36%. The median duration of response was 36 weeks (range 19.0~40.5). The median time to progression and survival duration were 17.5 and 69 weeks, respectively, for assessable patients. One hundred fifty cycles (median, five) of docetaxel were administered. Among 27 patients assessable for toxicity, the following side effects were reported: nadir neutropenia grade 3 (4 patients) and grade 4 (22 patients); grade 2 stomatitis (6 patients); grade 2 alopecia (5 patients); grade 2 to 3 neurosensory toxicity (4 patients); no hypersensitivity reaction; mild fluid retention (4 patients). CONCLUSION: Docetaxel is an active agent in patients with antracycline-pretreated metastatic breast cancer. Docetaxel was associated with severe but reversible neutropenia. Dexamethasone prevented hypersensitivity reactions and appeared to ameliorate fluid retention.

Seroepidemiologic Study of Brucellosis in Cheju Island / 감염

BACKGROUND: Brucellosis is a zoonosis caused by the gram-negative coccobacilli Brucella. Humans are infected by ingestion of unpasteurized milk or dairy products from or by direct contact with infected animals. Although human brucellosis is known to be rare, there has been an increase in bovine brucellosis in Cheju island since the 1980s. The purpose of this study was to investigate the prevalence of anti- Brucella antibody in people from endemic areas. METHODS: Sera obtained from 2,372 residents in Cheju island were screened for anti-Brucella antibody by slide agglutination test and confirmed by duplicated tube agglutination test. Sera with titers equal to or above 1:80 were considered positive. RESULTS: Fourteen of 2,372 sera were positive (0.59%). Positive rate was 0.34% in males and 0.82% in females. There was no significant difference in the positive rates between males and females. Seropositive rate was slightly higher in persons at 40 years or older. Seropositive rates in different areas of Cheju island were as follows : South Cheju-gun 0.97%, North Cheju-gun 0.64%, Cheju city 0.46%, and Sogwipo city 0.0%. The antibody titers of positive sera were determined: 7 sera were positive at 1:80, 4 at 1:160, and 3 were positive at 1:320. Occupations of seropositive persons were as follows : 7 farmers; 3 stockbreeders; 1 engaged in service trade; 1 engaged in food processing; 1 working at a stable; one unknown. Seropositive rates among people at a relatively high risk were 0.94%. Seropositive rate of people who were proven to be not at risk for Brucella infection was 0.51%. There was no significant difference in the seropositive rates between the two groups(P>0.05). CONCLUSION: These findings confirmed the occurrence of human Brucella infection in Cheju island and suggest the need for surveillance in other parts of the country as well.