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Biomedical subjects

K Hata

Publications and source records attributed to K Hata.

At least 37 records · Page 2Linked to original sources
PubMed2002

Utility of color Doppler indices of dominant follicular blood flow for prediction of clinical factors in in vitro fertilization-embryo transfer cycles.

OBJECTIVE: To investigate the relationship between color Doppler indices of dominant follicular blood flow and clinical factors in in vitro fertilization-embryo transfer cycles. SUBJECTS AND METHODS: This was a prospective study involving 26 patients completing a total of 33 in vitro fertilization cycles. Dominant follicular blood flow indices, peak systolic velocities, the resistance index and the pulsatility index were evaluated using transvaginal color Doppler. The indices were compared to the clinical outcomes of in vitro fertilization-embryo transfer. RESULTS: There was a significant correlation between dominant follicular peak systolic velocities and the number of oocytes retrieved, as well as the number of mature oocytes obtained. There was no significant correlation between dominant follicular resistance index or pulsatility index and the number of follicles > 10 mm in diameter, the number of oocytes retrieved or the number of mature oocytes. There were no significant differences between dominant follicular peak systolic velocities, resistance index or pulsatility index, and fertilization rate or the ratio of good quality embryos. However, significant differences were found between the number of oocytes retrieved, as well as the number of mature oocytes for those patients in which the peak systolic velocity was below 25 cm/s. CONCLUSIONS: Doppler assessment of dominant follicle blood flow alone is useful for predicting the number of retrievable oocytes. However, morphological quality of the embryo produced or the pregnancy rate cannot be predicted by this method.

Adult↗
PubMed2002

Interleukin-17 stimulates chemokine (interleukin-8 and monocyte chemoattractant protein-1) secretion in human pancreatic periacinar myofibroblasts.

BACKGROUND: Interleukin (IL)-17 is a newly identified T-cell-derived cytokine that can regulate the functions of a variety of cell types. In this study, we investigated the effects of CD4+ T-cell-derived cytokines on chemokine secretion in human pancreatic periacinar myofibroblasts. METHODS: The secretion of IL-8 and monocyte chemoattractant protein (MCP)-1 was evaluated by ELISA and Northern blot. The expression of IL-17 receptor (R) was analyzed by Northern blot and a binding assay using 125I-labeled IL-17. The activation of nuclear factor-kappaB (NF-kappaB) was assessed by an electrophoretic gel mobility shift assay (EMSA). RESULTS: IL-17 induced a dose-dependent increase in IL-8 and MCP-1 secretion. The effects of IL-17 on IL-8 and MCP-1 mRNA abundance reached a maximum as early as 3 h. and then gradually decreased. IL-17 and IFN-gamma synergistically increased IL-8 secretion and additively enhanced MCP-1 secretion. IFN-gamma induced a weak increase in IL-17R mRNA abundance, but incubation with IFN-gamma for 24 h had no effects on 125I-labeled IL-17-binding, indicating that the co-stimulatory effects of IL-17 and IFN-gamma were not regulated by the modulation of IL-17R expression. Furthermore, IL-17 induced a rapid increase in NF-kappaB DNA-binding activity, and the combination of IL-17 and IFN-gamma further enhanced NF-kappaB DNA-binding activity. CONCLUSIONS: In conclusion, it becomes clear that IL-17 is an inducer of IL-8 and MCP-1 secretion in human pancreatic periacinar myofibroblasts. The combination of IL-17 with IFN-gamma further enhances chemokine secretion. These findings indicate a linkage between T-cell-mediated immunity and inflammatory responses in the pancreas.

Blotting, Northern↗
PubMed2001

Application of 2-aminopyridine fluorescence labeling in the analysis of in vivo and in vitro metabolism of dextran sulfate sodium by size-exclusion high-performance liquid chromatography.

The present study describes a size-exclusion high-performance liquid chromatographic method for the separation and quantification of sulfated polysaccharides, such as dextran sulfate sodium (DSS). Pyridylamination of DSS was achieved without difficulty using 2-aminopyridine as a fluorometric label. In addition, 0.1-0.2 M phosphate buffer (pH 3.0) was found to be the mobile phase which produced the best separation. In vitro enzymatic degradation of the pyridylamino-DSS (PA-DSS5000, Mr 5000) using alpha-amylase and the in vivo metabolism in the rat feces after oral administration of PA-DSS5000 were then evaluated. Two small peaks of approximately Mr 380 and 600 appeared after co-incubation with alpha-amylase, indicating PA-DSS5000 may be considerably depolymerized. In vivo, however, PA-DSS5000 excreted in the feces was mainly of PA-DSS5000 polymer. No peaks of less than Mr 5000 were not clearly detectable in the feces because of background fluorescence attributable to gut lumen contents. This method of fluorometric analysis allows fairly selective detection of sulfated polysaccharides in biological materials.

Aminopyridines↗
PubMed2001

Atomically resolved local variation of the barrier height of the flip-flop motion of single buckled dimers of Si(100).

The dynamics of the flip-flop motion of single buckled dimers of Si(100) was elucidated by locating the tip of a scanning tunneling microscope over a single flip-flopping dimer and measuring the tunneling current (time trace). Based on a statistical analysis of the time trace, we succeeded in estimating the activation energy and the energy splitting between the two stable configurations of buckling. Strong dependence of the dynamics of the flip-flop motion on the local environment was found: Activation energy differs significantly (directly measured 32 meV, estimated approximately 110 meV) for dimers in different domains.

Journal Article↗
PubMed2001

Bud emergence is gradually delayed from S to G2 with progression of growth phase in Cryptococcus neoformans.

The G2 index of the yeast Cryptococcus neoformans determined by laser scanning cytometer was 2-3 times higher than the budding index during transition to the stationary phase of the culture, indicating that buds emerged in the G2 phase of the cell cycle. To clarify whether buds also emerge in G2 during exponential growth of the culture, DNA content for each cell was measured with a fluorescence microscope equipped with a photomultiplier. The DNA content of cells having tiny buds varied rather widely, depending on growth phases and strains used. Typically, buds of C. neoformans emerged soon after initiation of DNA synthesis in the early exponential phase. However, bud emergence was delayed to G2 during transition to the stationary phase, and in the early stationary phase budding scarcely occurred, although roughly half of the cells completed DNA synthesis. Thus, the timing of budding in C. neoformans was actually shifted to later cell cycle points with progression of the growth phase of the culture.

Cryptococcus neoformans↗
PubMed2001

Optical resolution of asymmetric triacylglycerols by chiral-phase high-performance liquid chromatography.

A simple method for direct optical resolution of some asymmetric triacylglycerols (TGs) has been established. The method employs chiral-phase high-performance liquid chromatography (HPLC). An enantiomeric pair of TGs comprising 1-eicosapentaenoyl-2,3-dicapryroyl-sn-glycerol (ECC) and 1,2-dicapryroyl-3-eicosapentaenoyl-sn-glycerol (CCE) was resolved on a CHIRALCEL OF or on a CHIRALCEL OD column. The separation of another pair of asymmetric TGs, 1-docosahexaenoyl-2,3-dicapryroyl-sn-glycerol (DCC) and 1,2-dicapryroyl-3-docosahexaenoyl-sn-glycerol (CCD), was achieved with the CHIRALCEL OD column. The chiral-phase HPLC method in combination with silver-ion HPLC and high-temperature gas chromatography was used for monitoring two interesterification reactions, whose products were chiral TGs. Interesterification of tricapryloylglycerol with ethyleicosapentaenoate or with ethyldocosahexaenoate was performed using Rhizomucor miehei lipase as the catalyst. The products targeted were the asymmetric pair of TGs, ECC and CCE or DCC and CCD. The amounts of sn-1-substituted products (ECC or DCC) were greater than their sn-3-substituted counterparts (CCE or CCD) throughout the reaction period, suggesting that R. miehei lipase had a stereopreference towards the sn-1 position over the sn-3 position.

Chromatography, High Pressure Liquid↗
PubMed2001

Development of fulminant hepatitis B (precore variant mutant type) after the discontinuation of low-dose methotrexate therapy in a rheumatoid arthritis patient.

A 75-year-old female rheumatoid arthritis patient who was positive for hepatitis B surface antigen and for antibodies to hepatitis Be antigen showed liver dysfunction, and therefore methotrexate (MTX) therapy was discontinued. Her drug lymphocyte stimulation test indicated positivity for MTX. Her liver dysfunction improved briefly, but she developed fulminant hepatitis with elevated levels of hepatitis B virus (HBV)/DNA polymerase and subsequently died. HBV/DNA analysis performed with polymerase chain reaction-mutation site-specific assay revealed that the fulminant hepatitis was caused by a precore mutant virus. Sudden reactivation of the immune system by discontinuation of MTX may have led to the attack on infected cells. Even when hepatitis Be antibodies are present, MTX should not be used in patients who have chronic infection with HBV.

Arthritis, Rheumatoid↗
PubMed2001

Preoperative assessment of vascularity by color Doppler ultrasonography in human rectal carcinoma.

PURPOSE: Although angiogenesis assessed by immunostaining endothelial cells (microvessel density) is a well-known prognostic factor in a wide variety of human solid tumors, preoperative determination of microvessel density seems to be difficult in rectal carcinoma. Thus, we performed transanal color Doppler ultrasonography in 46 patients with rectal carcinoma to assess preoperative angiogenic status and compare it with microvessel density in surgical specimens. METHODS: Time-averaged maximal velocity, peak systolic velocity, number of vascular points, and vascular point index were conducted by color Doppler ultrasonography in 46 patients with rectal carcinoma. Number of vascular points was defined as the number of vessels with pulsation in the section of tumor. Vascular point index was defined as the average number of vascular points divided by the area assessed by color Doppler ultrasonography in the section of tumor. The profiles of number of vascular points were similar to those assessed by microangiography in five rectal carcinomas. RESULTS: Vascular point index significantly correlated with microvessel density (P < 0.0001). No significant correlation was found between microvessel density and time-averaged maximal velocity or peak systolic velocity. Vascular point index was also a better indicator of lymph node metastasis and venous invasion than microvessel density. In addition, 11 of 46 cases with postoperative hematogenous metastasis (23.9 percent) were observed prospectively. Vascular point index may be a best predictor for hematogenous metastasis from rectal carcinoma compared with peak systolic velocity, time-averaged maximal velocity, and microvessel density by receiver operating characteristic analysis. CONCLUSION: These results suggest that preoperative quantification of angiogenesis using color Doppler ultrasonography will provide quick and useful information in the management of rectal carcinoma.

Blood Flow Velocity↗
PubMed2001

The characterization of superoxide production of human neonatal neutrophil.

To assess the role of neutrophil in neonatal host defense against microbial infection, we characterized the superoxide anion (O(2-)) production of neonatal neutrophil on a biochemical basis. After taking an appropriate informed consent, neutrophils were obtained from cord blood immediately after transvaginal delivery and divided into two groups: the Preterm group, 15 neonates (27-36 weeks' gestation) and the Term group, 15 neonates (37-41 weeks' gestation). Eleven healthy adults served as controls in the Adult group. The value of N-formyl-methionyl-leucyl-phenylalanin (fMLP)-induced O(2-) production activity of neutrophils in the Preterm group using chemiluminescence assay was significantly lower than those values in both the Term and Adult groups (5.77+/-0.53x10(6) vs. 11.1+/-0.94x10(6) and 10.7+/-0.63x10(6) cpm; mean+/-S.E.M., p<0.05). In phorbol 12-myristate 13-acetate (PMA)-stimulation, the values of O(2-) production activity of neutrophils in both the Preterm and Term groups were significantly lower than that in the Adult group (13.0+/-1.66x10(6) and 18.0+/-1.44x10(6) vs. 27.3+/-1.45x10(6) cpm, p<0.05). Scatchard analysis of [(3)H]fMLP binding to neutrophil demonstrated a two-receptor model in each group, and the number of high-affinity receptors per neutrophil in the Preterm group was significantly lower than those in other groups (p<0.05). However, cord blood levels of proinflammatory cytokines, such as interleukin (IL)-6, -8, and tumor necrosis factor-alpha (TNF-alpha) did not differ in either neonatal group. These results indicated that the fMLP-induced O(2-)production activity of neutrophils in the term neonates was enhanced at the level of the receptor and suggested that this enhanced production contribute to the neonatal host defense against microbial infection.

Adult↗
PubMed2001

Cooperation of interleukin-17 and interferon-gamma on chemokine secretion in human fetal intestinal epithelial cells.

Interleukin (IL)-17 is a newly identified T cell-derived cytokine that can regulate the functions of a variety of cell types. In this study, we investigated the effects of IL-17 and interferon (IFN)-gamma on chemokine secretion in human fetal intestinal epithelial cells. IL-8 and monocyte chemoattractant protein (MCP)-1 secretion by the human fetal intestinal epithelial cell line, intestine-407, was evaluated by ELISA and Northern blot. The expression of IL-17 receptor (R) was analysed by a binding assay using [(125)I]-labelled IL-17. The activation of nuclear factor-kappa B (NF-kappa B), NF-IL6 and AP-1 was assessed by an electrophoretic gel mobility shift assay (EMSA). IL-17 induced a dose-dependent increase in IL-8 and MCP-1 secretion. The inducing effects of IL-17 on IL-8 and MCP-1 mRNA abundance reached a maximum as early as 3 h, and then gradually decreased. IL-17 and IFN-gamma synergistically increased IL-8 and MCP-1 secretion and mRNA abundance. IFN-gamma induced a weak increase in IL-17 R mRNA abundance, and incubation with IFN-gamma for 24 h enhanced [(125)I]-labelled IL-17-binding by 2.4-fold. IL-17 rapidly induced the phosphorylation and degradation of I kappa B alpha molecules, and the combination of IL-17 and IFN-gamma induced a marked increase in NF-kappa B DNA-binding activity as early as 1.5 h after the stimulation. Furthermore, this combination induced an increase in NF-IL-6 and AP-1 DNA-binding activity. In conclusion, it becomes clear that IL-17 is an inducer of IL-8 and MCP-1 secretion by human fetal intestinal epithelial cells. The combination of IL-17 with IFN-gamma synergistically enhanced chemokine secretion. These effects of IL-17 and IFN-gamma might play an important role in the inflammatory responses in the intestinal mucosa.

Cell Line↗
PubMed2001

Plasma brain natriuretic peptide as a novel therapeutic indicator in idiopathic dilated cardiomyopathy during beta-blocker therapy: a potential of hormone-guided treatment.

BACKGROUND: Plasma brain natriuretic peptide (BNP) is a sensitive and specific marker of left ventricular (LV) function. In the treatment of heart failure, especially in idiopathic dilated cardiomyopathy (IDC), beta-blocker (BB) therapy has been established as a powerful strategy. The purpose of this study was to analyze relationships between changes in BNP level and LV function during BB therapy in patients with IDC. METHODS: In 30 patients with IDC who had already received conventional therapy, measurement for plasma BNP and norepinephrine levels and echocardiographic indices were evaluated before and 2 and 6 months after carvedilol in 21 patients and at baseline and after 6 months in 9 patients who did not receive carvedilol. RESULTS: After 6 months carvedilol treatment significantly improved LV end-diastolic dimension (LVEDD) (65 +/- 8 to 61 +/- 8 mm) and LV ejection fraction (LVEF) (34% +/- 13% to 43% +/- 12%) with intergroup differences; it significantly decreased BNP (127 +/- 113 to 69 +/- 92 pg/mL) with no intergroup difference; however, it did not decrease norepinephrine. BNP correlated strongly with LVEDD, LVEF, and LV mass index in carvedilol-treated patients. The degree of change in BNP correlated with that in LVEDD or LVEF 6 months after carvedilol. All 14 patients with decreased or unchanged BNP levels showed an increase in LVEF, and 4 of 7 with a rise in BNP had decreased or unchanged LVEF. According to receiver operating characteristic analysis, the optimal BNP levels for detecting LVEF <35% before and after carvedilol were 75.5 and 69 pg/mL, respectively. CONCLUSION: Plasma BNP levels may accurately reflect alteration in LV function and structure and can be used as a therapeutic indicator for risk stratification in patients with IDC during BB therapy.

Adrenergic beta-Antagonists↗
PubMed2001

Microtubules and actin cytoskeleton in Cryptococcus neoformans compared with ascomycetous budding and fission yeasts.

Actin cytoskeleton and microtubules were studied in a human fungal pathogen, the basidiomycetous yeast Cryptococcus neoformans (haploid phase of Filobasidiella neoformans), during its asexual reproduction by budding using fluorescence and electron microscopy. Staining with rhodamine-conjugated phalloidin revealed an F-actin cytoskeleton consisting of cortical patches, cables and cytokinetic ring. F-actin patches accumulated at the regions of cell wall growth, i. e. in sterigma, bud and septum. In mother cells evenly distributed F-actin patches were joined to F-actin cables, which were directed to the growing sterigma and bud. Some F-actin cables were associated with the cell nucleus. The F-actin cytokinetic ring was located in the bud neck, where the septum originated. Antitubulin TAT1 antibody revealed a microtubular cytoskeleton consisting of cytoplasmic and spindle microtubules. In interphase cells cytoplasmic microtubules pointed to the growing sterigma and bud. As the nucleus was translocated to the bud for mitosis, the cytoplasmic microtubules disassembled and were replaced by a short intranuclear spindle. Astral microtubules then emanated from the spindle poles. Elongation of the mitotic spindle from bud to mother cell preceded nuclear division, followed by cytokinesis (septum formation in the bud neck). Electron microscopy of ultrathin sections of chemically fixed and freeze-substituted cells revealed filamentous bundles directed to the cell cortex. The bundles corresponded in width to the actin microfilament cables. At the bud neck numerous ribosomes accumulated before septum synthesis. We conclude: (i) the topology of F-actin patches, cables and rings in C. neoformans resembles ascomycetous budding yeast Saccharomyces, while the arrangement of interphase and mitotic microtubules resembles ascomycetous fission yeast Schizosaccharomyces. The organization of the cytoskeleton of the mitotic nucleus, however, is characteristic of basidiomycetous yeasts. (ii) A specific feature of C. neoformans was the formation of a cylindrical sterigma, characterized by invasion of F-actin cables and microtubules, followed by accumulation of F-actin patches around its terminal region resulting in development of an isodiametrical bud.

Actin Cytoskeleton↗
PubMed2001

Sequential changes in luminal microflora and mucosal cytokine expression during developing of colitis in HLA-B27/beta2-microglobulin transgenic rats.

BACKGROUND: Transgenic rats expressing HLA-B27 and human beta2-microglobulin (HLA-B27 rats) spontaneously develop chronic colitis resembling human inflammatory bowel disease. We investigated the sequential changes in the luminal bacterial flora and mucosal cytokine mRNA expression in this model. METHODS: HLA-B27 rats were maintained in a specific pathogen-free environment, and luminal microflora was evaluated by standard bacterial culture technique. The expression of mucosal cytokine mRNA was analysed by RT-PCR methods. RESULTS: Clinical symptoms of colitis appeared at 8 weeks of age. The total number of obligate anaerobes was higher than those of facultative anaerobes during the experimental period. At 6 weeks of age, the colonization of Bacteroides spp., Bifidobacterium spp. and Lactobacillus spp. was already detectable at high concentrations, whereas Clostridium spp. and Eubacterium spp. were not detected. The expression of proinflammatory cytokines (IL-Ibeta, IL-8 and TNF-alpha) appeared at 8 weeks of age, and these were detectable until 17 weeks. A similar pattern was observed in the expression of Th1 cytokines (IL-2, IL-12 and IFN-gamma). On the other hand, the expression of Th2 cytokines (IL-4, IL-10 and TGF-beta) was weak. IL-4 mRNA expression was weakly detectable only at 6 and 8 weeks of age. The expression of IL-10 and TGF-beta mRNA was scarcely detectable throughout the experimental period. CONCLUSION: The development of colitis may be mediated by both the predominant expression of Th1 cytokines and the weakness of Th2 cytokine expression in the mucosa. The colonization of anaerobic bacteria, especially Bacteroides spp., may be initiating and promoting these cytokine responses.

Animals↗
PubMed2001

Intestinal perforation due to metastasis of breast carcinoma, with special reference to chemotherapy: a case report.

We report a case of small-bowel perforation due to metastatic carcinoma of the breast during chemotherapy. Partial resection of the small intestine and primary anastomosis were performed. Although the patient made a good recovery from panperitonitis, she died of the disease on the 55th postoperative day. Since perforation during chemotherapy results in an extremely poor prognosis, special caution during chemotherapy is needed for patients with possible gastrointestinal involvement with tumor.

Adenocarcinoma↗
PubMed2001

Clinical value of thymidine kinase in patients with cervical carcinoma.

OBJECTIVE: Our purpose was to determine the clinical value of thymidine kinase (TK), which is an important pyrimidine pathway enzyme involved in salvage DNA synthesis, in patients with cervical carcinoma. METHODS: We examined TK mRNA expression by reverse transcription polymerase chain reaction in 19 tissue specimens of invasive cervical carcinoma and 9 normal cervices and related it to thymidylate synthase (TS) and thymidine phosphorylase (TP) mRNA expressions. Serum TK level was determined by radioenzymatic assay in 79 patients with invasive cervical carcinoma, 7 patients with microinvasive carcinoma, 21 patients with carcinoma in situ and 32 normal women. RESULTS: TK mRNA expression was upregulated in invasive cervical carcinoma compared with the normal cervix (p < 0.05) and significantly correlated with TS mRNA expression (p < 0.0001) but not with TP mRNA expression. The serum TK level was significantly higher in patients with invasive carcinoma than in normal women and patients with carcinoma in situ (p < 0.01 and p < 0.05). In patients with invasive cervical carcinoma, the serum TK level significantly correlated with TK mRNA expression (p < 0.05), but not with any conventional clinicopathologic factors. High serum TK levels significantly correlated with a poorer survival (p < 0.05), and multivariate analysis showed serum TK level to be an independent prognostic factor (p < 0.05). CONCLUSION: TK may play an important role in influencing the malignant behavior of cervical carcinoma, and measurement of the serum TK level may be useful in predicting survival in patients with cervical carcinoma.

Adult↗
PubMed2001

[Nitric oxide spares myocardial oxygen consumption through attenuation of contractile response to beta-adrenergic stimulation in patients with idiopathic dilated cardiomyopathy].

BACKGROUND: The results of recent studies suggest that nitric oxide (NO) synthase may increase in the failing myocardium and that NO modulates the myocardial contractile response to beta-adrenergic stimulation. However, there are few data regarding the physiological role of NO in patients with heart failure. The aim of the present study was to address the role of NO in left ventricular contractile response to beta-adrenergic stimulation and corresponding oxygen expenditure in human heart failure. METHODS AND RESULTS: We studied 15 patients with heart failure due to idiopathic dilated cardiomyopathy (mean ejection fraction 0.33). We examined left ventricular contractility (Emax, the slope of end-systolic pressure-volume relation), left ventricular external work (EW), myocardial oxygen consumption (MVO2), and mechanical efficiency (measured as EW/MVO2) with the use of conductance and coronary sinus thermodilution catheters before and during dobutamine (DOB) infusion via a peripheral vein (4.8 +/- 0.3 micrograms.kg-1.min-1 i.v.). Heart rate was kept constant with atrial pacing. We carried out a similar protocol during the intracoronary infusion of the NO synthase inhibitor NG-monomethyl-L-arginine (L-NMMA; 200 mumol). DOB increased Emax, EW, and MVO2 (by 77 +/- 17%, 39 +/- 5%, and 21 +/- 5%, respectively), leading to an increase in mechanical efficiency (25.4 +/- 3.1% to 29.6 +/- 4.1%). L-NMMA alone did not significantly change these variables. Although the concurrent infusion of DOB with L-NMMA increased Emax, EW, and MVO2 (by 140 +/- 21%, 64 +/- 9%, and 35 +/- 5%, respectively) more than DOB alone, mechanical efficiency did not increase further (24.3 +/- 3.3% to 29.5 +/- 4.5%) because EW and MVO2 increased in parallel. CONCLUSIONS: These data suggest that in patients with idiopathic dilated cardiomyopathy, endogenous NO spares MVO2 through attenuation of left ventricular contractile response to beta-adrenergic stimulation while maintaining left ventricular energy-converting efficiency.

Cardiomyopathy, Dilated↗
PubMed2001

Expression of the Endostatin gene in epithelial ovarian cancer.

Endostatin, a M(r) 20,000 COOH-terminal fragment of collagen XVIII, is currently in preclinical development as a novel antiangiogenic agent. The gene expression of this molecule in 23 normal ovaries with follicle or corpus luteum and in 64 cases of epithelial ovarian cancer (27 serous, 18 mucinous, 13 endometrioid, 4 clear cell, and 2 undifferentiated carcinomas) was analyzed by PCR of RNA after reverse transcription. Seven of the cases were of low malignant potential. With regard to staging, 23 cases had stage I disease, 5 had stage II disease, 29 had stage III disease, and 7 had stage IV disease. The level of endostatin gene expression was described in terms of the ratio of the relative yield of the endostatin gene to that of the beta2-microglobulin gene. Endostatin gene expression in ovarian cancers (median, 0.14; range, 0.02-1.11) was significantly higher than that in normal ovaries with follicle or corpus luteum (median, 0.08; range, 0.03-0.26; P = 0.009). International Federation of Gynecology and Obstetrics stage (P = 0.009) and residual tumor (P = 0.005) were significantly associated with endostatin gene expression; however, other clinicopathological features (e.g., patient age at diagnosis, histological subtype, and histological grade) were not significantly associated with endostatin gene expression. Survival data were available for all patients. Univariate Cox regression analysis showed the prognosis of the patients with high endostatin gene expression [equal to or greater than the median (> or =0.14)] to be significantly worse than that of patients with low endostatin gene expression [less than the median (<0.14); P = 0.044]. Our results with regard to the gene expression of this endogenous inhibitor of angiogenesis present a new insight to understand the biology of epithelial ovarian cancer and may lead to the development of a new therapeutic strategy for epithelial ovarian cancer.

Collagen↗