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.
Basement Membrane ; Breast Neoplasms* ; Breast* ; Cytosol ; Enzyme-Linked Immunosorbent Assay ; Estrogens ; Extracellular Matrix ; Humans ; Multivariate Analysis ; Plasminogen Activators* ; Plasminogen* ; Urokinase-Type Plasminogen Activator*

Soluble forms of ICAM-1 (sICAM-1) and VCAM-1 (sVCAM-1) have been reported from the supernatant of cytokine-activated endothelial cells, cancer cells and from sera of cancer patients. We measured sICAM-1 and sVCAM-1 from the serum of 20 healthy volunteers and 142 gastric cancer patients by ELISA assay. Ninety-five patients were operable and 47 patients were in-operable at the time of this study. Particularly in the 28 operable patients, we sampled both portal and peripheral blood simultaneously and measured the levels of the soluble forms of cell adhesion molecules (sCAMs). The sCAMs level and sero-positivity rate increased with cancer progression in order of the healthy controls, operable patients, and inoperable patients. In in-operable cancer, the sICAM-1 level increased more with liver metastasis. sICAM-1 and sVCAM-1 did not correlate with each other in either portal or peripheral blood. A total of 58.3% of patients with liver metastasis and 22.9% of patients without liver metastasis showed synchronous expression of both sCAMs (p = 0.03). Synchronous sero-positivity of sCAMs and alpha FP was higher with liver metastasis (p = 0.01). The median overall survival duration which co-expressed both sCAMs was 9 months. This showed a significant difference compared with the sICAMs non-expressing group, where the median survival was not reached until 24 months follow-up (p = 0.002). The synchronous expression of sCAMs was an independent risk factor in gastric cancer patients. We raise the possibility that synchronous sICAM-1 and sVCAM-1 elevation may be a useful monitor to determine tumor burden in gastric cancer.
Adult ; Aged ; Female ; Human ; Intercellular Adhesion Molecule-1/blood* ; Liver Neoplasms/secondary ; Male ; Middle Age ; Stomach Neoplasms/mortality ; Stomach Neoplasms/blood* ; Survival Rate ; Vascular Cell Adhesion Molecule-1/blood*

BACKGROUND: Body mass index is currently applied as the diagnostic standard of overweight and obesity, regardless of age. Percentage body fat ratio applies separate standards among different sex, but does not have separate standards for different age groups. Since body mass index and percentage body fat may differ according to age, we conducted this study to see if a separate standard for overweight and obesity is indeed necessary for different age groups. METHODS: We selected 2,190 subjects, who were the 10 percent picked randomly by computer, among 21,921 clients who had visited the St. Mary's Hospital's health promotion center in Seoul. Those diagnosed with diabetes, thyroid disease, renal failure, and tuberculosis were excluded, leaving 1,939 over the age of 20, as final subjects. Anthropometric measurements were done using electronic scales and height meters, while body composition was measured with a multi-frequency bioelectric impedance analysis (Inbody 3.0 Biospace, Seoul). The results of this study were shown in mean and standard deviation, and mean values according to ages were compared by Ancova test. RESULTS: In the case of adult men, percentage body fat increased with age. This was observed especially with subjects over 30 compared to subjects in their 20s, although not proven to be statistically significant. A decrease in fat free mass rather than increase in body fat mass was noted with aging. With adult women, percentage body fat increased markedly with subjects over 50, mainly due to increased body fat mass rather than decreased fat free mass. Subjects exceeding a body mass index of 25, which is the standard limit of body mass index for obesity, was 60th percentile for adult men, and 70~80th percentile for adult women. Percentage body fat in this case was 22.54% for men and 31.99~33.46% for women. CONCLUSION: Our study indicates that both men and women show changes in body mass index and fat free mass with aging. Hence, there are limitations to applying a universal standard for body mass index, regardless of age. We suggest that further studies on standards for adult obesity should be conducted based on specific Korean epidemiologic data.
Adipose Tissue* ; Adult ; Aging ; Body Composition ; Body Fat Distribution* ; Body Mass Index* ; Electric Impedance ; Female ; Health Promotion ; Humans ; Male ; Obesity ; Overweight ; Renal Insufficiency ; Seoul ; Thyroid Diseases ; Tuberculosis ; Weights and Measures

A 45-year-old woman who complained of weight gain and irregular menstruation was diagnosed as having Cushing's syndrome due to a 3 cm sized left adrenal adenoma. She underwent left adrenalectomy, and she also underwent combined anterior pituitary tests before and 9 months after the surgery. The growth hormone and adrenocorticotropic hormone levels failed to respond to hypoglycemia before the surgery, but their responses recovered after the surgery. Cortisol and thyroid stimulating hormone failed to respond to hypoglycemia and thyrotropin releasing hormone (TRH) before the surgery, respectively, but these were improved after the surgery. Luteinizing hormone, follicle stimulating hormone, and prolactin adequately responded to gonadotropin-releasing hormone and TRH, respectively, before and after the surgery. However, the basal levels of these hormones were higher after adrenalectomy, suggesting that hypercortisolemia had a significant influence on all the pituitary hormones.
Adenoma* ; Adrenalectomy ; Adrenocorticotropic Hormone ; Cushing Syndrome* ; Female ; Follicle Stimulating Hormone ; Gonadotropin-Releasing Hormone ; Growth Hormone ; Humans ; Hydrocortisone ; Hypoglycemia ; Hypopituitarism ; Luteinizing Hormone ; Menstruation ; Middle Aged ; Pituitary Hormones ; Prolactin ; Thyrotropin ; Thyrotropin-Releasing Hormone ; Weight Gain

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.
Gabexate* ; Humans ; Inhibitory Concentration 50 ; Lymph Nodes ; Matrix Metalloproteinases ; MMPI ; Multivariate Analysis ; Neoplasm Metastasis ; Patient Selection* ; Phenotype ; Population Characteristics ; Prognosis ; Stomach Neoplasms*

PURPOSE: We evaluated the treatment efficacy including survival and recurrence, and factors associated with recurrence in osteosarcoma patients treated with preoperative chemotherapy, surgery, and adjuvant chemotherapy. MATERIALS AND METHODS: Forty nine patients with osteosarcoma were treated with preoperative chemotherapy with intra-arterial cisplatin and adriamycin infusion for 3 cycles, followed by surgery. According to the pathologic response, if tumor was necrotized more than 90%, the same adjuvant chemotherapy was reintroduced for 3 cycles, and if the response was not enough, then the salvage regimen was introduced. Plain chest film and chest CT scan were taken monthly and every 3 months, respectively. When tumor recurred, the metastasectomy was performed whenever possible. RESULTS: Forty three patients were evaluable with amedian follow up of 53 months. Five-year disease-free and overallsurvival rate was 47.0% and 66.9%, respectively. The recurrence was observed in 22 patients (51.2%) with median time of 12.5 months. Baseline alkaline phosphatase (ALP) was the only significant factor for recurrence (p=0.03) and the patients with the possibility of metastasectomy recurrence showed higher post-relapse survival compared to other treatment modalities (26 momths vs 5~12 months). CONCLUSION: These results indicates that pre- and postoperative chemotherapy with intra-arterial cisplatin and adriamycin infusion showed comparable treatment efficacy and acceptable toxicities.
Alkaline Phosphatase ; Chemotherapy, Adjuvant ; Cisplatin ; Doxorubicin ; Drug Therapy* ; Extremities* ; Follow-Up Studies ; Humans ; Metastasectomy ; Osteosarcoma* ; Recurrence ; Thorax ; Tomography, X-Ray Computed ; Treatment Outcome

PURPOSE: We evaluated the clinical significance of the tumor growth factor, midkine (MK), in paired gastric cancer and normal tissues. MATERIALS AND METHODS: Twenty paired normal and cancer tissues were tested for MK mRNA expression by Northern blot analysis. Vessel staining was done by immunohistochemical staining using CD-31 monoclonal antibody (Dako). RESULTS: MK mRNA was mainly expressed in cancer tissues (11 versus 1). Lymph node metastasis, pathological stage and tumor differentiation did not correlate with MK expression. However, MK expression rate increased with increment in tumor size (p=0.05). Microvascular density did not correlate with tumor invasion, lymph node metastasis, and pathological stages. However, there was a tendency of vascular density increment with MK expression in T1-T2 stage. CONCLUSION: MK was mainly expressed in larger gastric cancer tissues suggesting its role in cancer growth in vivo. But no definite correlation between MK expression and tumor microvascular density was found.
Blotting, Northern ; Gene Expression* ; Lymph Nodes ; Neoplasm Metastasis ; RNA, Messenger ; Stomach Neoplasms*

PURPOSE: We measured the gastric cancer tissue uPA and plasminogen activator inhibitor-1 (PAI-1) levels and compared them to those of the peripheral and portal blood levels to evaluate the correlation. MATERIALS AND METHODS: Tissue uPA and PAI-1 levels were measured by ELISA assay (Monozyme, Netherland) in paired 85 normal and cancer tissues resected from gastric cancer patients. In 50 patients, blood uPA and PAI-1 levels were measured from pre- operative peripheral and portal blood, post-operative portal blood. RESULTS: Gastric cancer tissue uPA and PAI-1 levels increased from the early stage. The elevated cancer-to-normal ratios of the uPA and PAI-1 were constant from stage I to IV. There were correlations of uPA between normal and cancer tissues (r2=0.38) and between peripheral and pre-resection portal blood level (r2=0.64). There were no correlations between tissue PAI-1 level and blood PAI-1 levels. However, there were correlations in PAI- 1/uPA ratio between cancer tissue and peripheral blood (r2=0.25), peripheral blood and pre- resection portal blood (r2=0.60). CONCLUSION: Even if the cancer tissue levels of uPA and PAI-1 increased from the early stage of gastric cancer, only blood uPA level correlated with tissue uPA level. A modest correlation found in PAI-1/uPA ratio between cancer tissue and blood suggests applicability of blood PAI-1/uPA ratio in predicting tissue uPA, PAI-1 expression.
Enzyme-Linked Immunosorbent Assay ; Humans ; Plasminogen Activator Inhibitor 1 ; Plasminogen Activators ; Stomach Neoplasms* ; Urokinase-Type Plasminogen Activator*

PURPOSE: The circulating forms of ICAM-1 (cICAM-1) and VCAM-1 (cVCAM-1) has been reported from supernatant of cytokine activated endothelial cells, cancer cells and from cancer patient serum even though the biological significance of the cCAMs are not fully elucidated. MATERIALS AND METHODS: To evaluate the correlation of the expression of cICAM-1 and cVCAM-1 and prognosis in gastric cancer, we measured cICAM-1 and cVCAM-1 levels in 20 healthy volunteers and 142 gastric cancer patients' sera by ELISA assay. Also we compared cCAMs levels with vascular endothelial growth factor (sVEGF) and FP. Ninety-five patients were operable and 47 patients were advanced or relapsed state at the time of the study. In 28 operable patients, we simultaneously sampled portal and peripheral vein and measured the cCAMs. RESULTS: The cCAMs level and positive rate in serum increased with cancer progression from healthy control, operable to advanced or relapsed gastric cancer. In advanced cancer, cICAM-1 level increased with liver metastasis. The cICAM-1 level in portal blood was correlated modestly with that in peripheral blood. And in cVCAM-1 positive subgroup, cCAM-1 level correlated with cVCAM-1 level. The peripheral cICAM-1 level decreased in 6% compared to that of portal cICAM-1 level while peripheral cVCAM-1 level increased in 1% compared to that of portal level. Synchronous expression of both cCAMs was found in 58.3% of the patients with liver metastasis and 22.9% of the patients without liver metastasis (p=0.03). But, there were no correlation between cCAMs and FP expression regardless of liver metastasis. The sVEGF level correlated with neither cICAM-1 nor cVCAM-1 level regardless of liver metastasis. The median disease-free and overall survival of patients with synchronous cICAM-1 and cVCAM-1 expression was 8 months and 9 months, while in patients without co-expression it was more than 24 months and 23 months respectively. CONCLUSION: We suggest that synchronous cICAM-1 and cVCAM-1 elevation may be a useful monitor of tumor burden and progression in gastric cancer, especially in liver metastasis.
Endothelial Cells ; Enzyme-Linked Immunosorbent Assay ; Healthy Volunteers ; Humans ; Intercellular Adhesion Molecule-1* ; Liver ; Neoplasm Metastasis ; Prognosis ; Stomach Neoplasms* ; Tumor Burden ; Vascular Cell Adhesion Molecule-1* ; Vascular Endothelial Growth Factor A ; Veins

PURPOSE: We studied biological phenotypes of gastric cancer cell lines based on a novel heparin-binding growth/differentiation factor, midkine (MK) expression. MATERIALS AND METHODS: Nine gastric cancer cell lines and 25 gastric cancer tissues were tested for MK expression by Northern blot analysis. Soft agar assay for in vitro tumorigenesis, cross- feeding assay for paracrine angiogenic activity, ELISA for uPA and PAI-1 measurement were performed. RESULTS: MK expression was found in 67% (6/9) of the gastric cancer cell lines, and 56% (14/25) of the primary gastric cancer tissues. Gastric cancer cell lines with MK expression were more tumorigenic in soft agar assay and endothelial cell growth stimulatory in cross-feeding assay than cells which did not express MK. However, urokinase-type plasminogen activator (uPA) expression did not correlate with MK expression. Growth of MK expressing cells was inhibited by a heparin-binding blocking agent, pentosan polysulfate (PPS). In cancer tissues, MK expression correlated with tumor size, suggesting in vivo autocrine and paracrine activity. CONCLUSION: Gastric cancer cells with increased MK gene expression showed increased tumorigenic and angiogenic activity. Therefore, this proliferation promoting activity of MK can be targeted by an anti-heparin binding agent as a biotherapy model in gastric cancer treatment.
Agar ; Biological Therapy* ; Blotting, Northern ; Carcinogenesis ; Cell Line ; Endothelial Cells ; Enzyme-Linked Immunosorbent Assay ; Gene Expression* ; Pentosan Sulfuric Polyester ; Phenotype* ; Plasminogen Activator Inhibitor 1 ; Stomach Neoplasms* ; Urokinase-Type Plasminogen Activator