PURPOSE: The inhibitory effect of TGFbeta1 on survivals of L1210 and anticancer drug- resistant L1210 sublines was investigated and the gene expression of TGFbeta1 in these cells was examined. MATERIALS AND METHODS: The survivals of L1210, adriamycin-resistant(L1210AdR), vincristine-resistant(L1210VcR) or cisplatin-resistant(L1210Cis) cells were measured by MTT assay after treatment of TGFbeta1. Northern analysis was performed for TGFbeta1 gene expression in L1210, L1210AdR, L1210VcR or L1210Cis. RESULTS: There was no different survival ratio between two groups, control and TGFbeta1(10 ng/ml) treated groups in L1210 cells. However, the survival ratio of L1210AdR was 59% in TGFbeta1 treated group for 96 hours. The survival ratio of L1210VcR was 61% for 96 hours in TGFbeta1 treated group. The survival ratio of L1210Cis was 40% for 96 hours in TGFbeta1 treated group. Expressions of TGFbeta1 gene in drug-resistant sublines were significantly decreased than that of L1210 cells. CONCLUSION: Growth of anticancer drug-resistant L1210 sublines were inhibited by TGFbeta1 but not in L1210 cells. So, it is suggested that TGFbeta1 gene expression may have a part in anticancer drug-resistance.
Control Groups ; Gene Expression

No abstract available.
3,4-Dihydroxyphenylacetic Acid* ; Animals ; Brain* ; Diazepam* ; Rats*

BACKGROUND: Carcinoma of the uterine cervix is a theoretically preventable disease because its precursor lesions can be detected by cervical Papanicolau smears and appropriately treated, Although cervical cytology screening programmes have resulted in the redution of cervical cancer incidence and mortality, Pap smear have been subjected to intense scrutiny and criticism in recent years. The focus of criticism has been the false-negative Pap smear, and the false-negative Pap smear is the major quality issue currently facing the physicians. To reduce the false-negative rate of Pap smear, it is essential to improve the accuracy of Pap smear. But false-negative rate of Pap smear has been reported variously. OBJECTIVE: This study was undertaken to evaluate accuracy of Pap smear by study false-negative and false-positive rate of Pap smear and to determine whether false-negative and false-positive rate had any correlations with clinical factors. STUDY DESIGN: The study population was comprised of 346 women, who were undertaken gynecologic operation at the Department of Obstetrics & Gynecology at Hanyang University hospital between March, 1997 and April, 1998. All patients were taken Pap smear before operation. In 93 women of these, preoperative diagnosis were cervical intraepithelial neoplasia and carcinoma in situ of uterine cervix, and in 253 women of these, preoperative diagnosis were benign disease as uterine myoma or adenomyosis, etc. All of their surgical specimen were examined. Pap smear, pathology, medical charts of all patients were reviewed retrospectively, and false-negative rate and false-positive rate were calculated. Clinical factors that associated with false-negative and false-positive rate were evaluated. Fishers exact test and Pearson chi-square test were used of statistical analysis, RESULTS: False-negative rate of Pap smear was 7.2%, false-positive rate was 4.6%, corresponding rate with histology was 88.2%. Sensitivity and specificity of PAP smear were 87.0% and 97.0% respctively. According to gross finding of uterine cervix, erosion was 46.6% in cervical intraepithelial neoplasia, 67.8% in carcinoma in situ, 66.6% in microinvasive carcinoma of uterine cervix and 55.3% of 103 erosion findings was cervical intraepithelial neoplasia, carcinoma in situ or microinvasive carcinoma. 23.1% of cervical lesion were normal gross finding. Menopause was associated with false-negative rate and previous vaginal infection history, previous cervical minor operation, delivery mode, contraception method, pelvic inflammatory disease history, vaginal bleeding at Pap smear and gross finding of cerbix were not associated. There were no clinical factors that were associated with false-positive rate. CONCLUSION: Compared with other reports, false-negative rate(7.2%) and false-positive rate(4.6%) of Pap smear was lower and corresponding rate(88.2%) was higher in Hanyand university hospital. Because of higher false-negative rate in menopausal women, it need more careful to take and interpretate Pap smear in these group.
Adenomyosis ; Carcinoma in Situ ; Cervical Intraepithelial Neoplasia ; Cervix Uteri ; Contraception ; Diagnosis ; Female ; Gynecology ; Humans ; Incidence ; Leiomyoma ; Mass Screening ; Menopause ; Mortality ; Obstetrics ; Pathology ; Pelvic Inflammatory Disease ; Retrospective Studies ; Sensitivity and Specificity ; Uterine Cervical Neoplasms ; Uterine Hemorrhage

PURPOSE: Increased expression of the hepatocytes growth factor (HGF) receptor (c-Met) and urokinase type plasminogen activator (uPA) correlate with the development and metastasis of cancers. However, the mechanisms by which HGF/c-Met signaling mediate cancer progression and metastasis are unclear. Therefore, we investigated the roles of HGF/c-Met in tumor progression and metastasis in pancreatic cancer cell lines, L3.6PL and IMIN-PC2. MATERIALS AND METHODS: To see the functional c-Met protein, we were performed immunoprecipitation for functional c-Met protein. And also performed western bolot analysis and gel zymography for the functional uPA protein. To see the inhibition effects of uPAR monoclonal antibody on invasiveness of two pancreatic cancer cell lines, we were carried out standard two chamber invasion assay. RESULTS: At first, we observed the HGF-mediated c-Met phosphorylation and cell growth. c-Met phosphorylation was increased in the HGF-treated cells in a dose dependent manner. HGF resulted in increments of cell growth and ERK phosphorylation. HGF treatment increased the uPA expression and the uPA activity. A monoclonal antibody 3936, specific to uPAR receptor, inhibited HGF- mediated tumor cell invasion in a dose dependent manner. CONCLUSION: These results suggest that functional c- Met and HGF/c-Met signaling up-regulate the activity of uPA and result in increments of invasion-metastasis in the pancreatic cancer cells.
Cell Line ; Hepatocytes* ; Humans* ; Immunoprecipitation ; Neoplasm Metastasis ; Pancreatic Neoplasms* ; Phosphorylation ; Plasminogen Activators* ; Plasminogen* ; Receptors, Urokinase Plasminogen Activator ; Urokinase-Type Plasminogen Activator*

Tumor cells are known to produce larger amounts of reactive oxygen species (ROS) than normal cells. Although numerous reports have indicated the importance of ROS in urokinase plasminogen activator (uPA) production, the precise mechanisms remain controversial. In our study, we investigated the effect of ROS on uPA generation in human hepatoma cells, HepG2 and Hep 3B. We determined the effects of hepatocyte growth factor (HGF) on the regulation of ROS, which resulted in suppression of ROS production, as measured with the fluorescent probe, 2'-7'-dichlorofluorescein diacetate. The role of HGF in modulating ROS production, particularly that regulated by Rac-1, was determined. HGF suppressed the increment in Rac-1-regulated ROS in both cell lines. Treatment with 200 microM of H2O2 showed a 1.6-2.1 fold increment in HGF, but a little increment occurred at 500 microM of H2O2. It looks no dose dependent manner. Combined treatment with H2O2 and HGF, resulted in a slightly increased production of HGF compared to no treatment (control). Also, H2O2 upregulated uPA expression in both hepatoma cell lines. To identify the downstream pathways regulated by ROS, we treated cells with PD 98059, an MEK inhibitor, and SB 203580, a p38 inhibitor, after treatment with H2O2, and showed negative control between ERK and p38 kinase activities for uPA regulation. We found that HGF modulate Rac-1-regulated ROS production through activation of Akt and ROS regulates uPA production via MAP kinase, which provides a novel clue to clarify the mechanism underlying hepatoma progression.
Cell Line, Tumor ; Fluorescent Dyes/chemistry ; Hepatocyte Growth Factor/pharmacology/*physiology ; Humans ; Hydrogen Peroxide/pharmacology ; Imidazoles/pharmacology ; Liver Neoplasms/drug therapy ; Mitogen-Activated Protein Kinases/antagonists & inhibitors/*metabolism ; Pyridines/pharmacology ; Reactive Oxygen Species/*metabolism ; Recombinant Proteins/pharmacology ; Urokinase-Type Plasminogen Activator/*biosynthesis ; rac1 GTP-Binding Protein/metabolism

No abstract available.
Liver* ; Ultrasonography*

No abstract available.
Biofeedback, Psychology* ; Headache* ; Humans ; Muscle Tonus*

PURPOSE: Various factors regulate interleukin(IL)-6 expression in mesangial cells (MCs). Immune complexes or angiotensin II(AII) are involved in the development of glomerulonephritis(GN). We evaluated the effects of IgG and IgA aggregates or AII on IL-6 mRNA expression in human MCs and the modulation by losartan, an AT1 receptor blocker, or hydrocortisone. METHODS: After 48 hours of culture in the presence of sera, IL-6 mRNA expression was analyzed by reverse transcription and polymerase chain reaction(PCR). RESULTS: Incubation of MCs with IgA or IgG aggregates(100 microgram/mL) as well as AII(10(-7) M) enhanced the ratio of PCR products for IL-6 to beta-actin on densitometric results. The addition of hydrocortisone(0.5 microgrammL) reduced the IgA aggregates-induced IL-6 mRNA expression and losartan(10(-6) M) reduced IgG aggregates- induced IL-6 mRNA expression. CONCLUSION: These results suggest that IgG and IgA aggregates and AII may induce IL-6 expression in GN which can be partially suppressed by hydrocortisone or AT1 receptor blocker.
Actins ; Angiotensin II* ; Angiotensins* ; Antigen-Antibody Complex ; Humans* ; Hydrocortisone* ; Immunoglobulin A ; Immunoglobulin G ; Interleukin-6* ; Losartan ; Mesangial Cells* ; Polymerase Chain Reaction ; Receptors, Angiotensin* ; Reverse Transcription ; RNA, Messenger*

Interleukin (IL)-6 is an autocrine growth factor for mesangial cells. It is not known whether high glucose influences IL-6 production in mesangial cells. Angiotensin II (AGII) is involved in the progression of renal diseases including diabetic nephropathy. Therefore, we evaluated the effects of high glucose in concert with AGII on IL-6 production in human mesangial cells and the modulation by blocking AGII. After 48 hr of culture, IL-6 mRNA expression was analyzed by reverse transcription and polymerase chain reaction (PCR). Quantitative determination of IL-6 concentrations in the culture supernatants of mesangial cells was performed using a sandwich enzyme immunoassay kit. Incubation of mesangial cells with high glucose (450 mg/dL) reduced the ratio of PCR products for IL-6 to beta-actin on densitometric results, while AGII (10(-7)M) increased it. The IL-6 secretion in the supernatant was also increased by AGII and decreased by high glucose. The IL-6 mRNA expression and IL-6 secretion in combination of high glucose and AGII were higher than those in high glucose and similar with those in control media. The addition of losartan (10(-6)M) or captopril (10(-6)M) to high glucose had no additional effects on IL-6 production. These results suggest that whereas AGII increases IL-6 production, high glucose decreases it. The IL-6 production of mesangial cells in diabetic milieu may be complicated and depend on the local effects of high glucose and/or AGII.
Angiotensin II/*pharmacology ; Captopril/pharmacology ; Cells, Cultured ; Gene Expression/drug effects ; Glomerular Mesangium/cytology/*metabolism ; Glucose/*pharmacology ; Humans ; Interleukin-6/*biosynthesis/genetics/secretion ; Losartan/pharmacology

Nitric oxide has been considered to be an important modulator of the epileptic seizure response. Previous studies have mainly focused on the nitric oxide synthase (NOS) expressed in glial cells and vascular endothelial cells in the brain following seizures, while less data have been available reading the change of neuronal NOS (nNOS) produced in neurons. Polypeptide growth factors play a central role in a variety of environmentally induce structural changes in the cortex and hippocampus of adult brain. neuregulin is widely expressed in the central and peripheral nerve cells and Schwann cells, glia, oligodendrocytes and muscle cells, to control cellular proliferation, differentiation and migration. erbB family are the receptors of the neuregulin and consist of erbB2, erbB3 and erbB4. We have, therefore, investigated the change in the expression of nNOS and erbB4 in the rat hippocampus, one of the brain structures most vulnerable to seizures. Rats were injected with kainic acid (KA) and sacrificed 6 h, 1 d, 3 d and 6 d after KA administration. The expression pattern of nNOS and erbB4 was studied using reverse transcription-polymerase chain reaction analysis, NADPH-diaphorase (NADPH-d) histochemistry and immunohistochemistry. The increase in the level of nNOS reached maximal values in samples obtained 1 d after KA treatment. The optical densities of NADPH-d-positive neurons in the CA1 and dentate gyrus (DG) regions of the hippocampus were shown to have increased in samples obtained 1 d and 3 d after injection of KA. The number of NADPH-d-positive neurons in the CA1 regions of the hippocampus was shown to have decreased in samples obtained 3 d and 6 d after injection of KA. However, the number of NADPH-d-positive neurons in the DG region did not change significantly. We show that erbB4 immunoreactivity is increased in hippocampus, reaching maximal levels 3 d after KA treatment, some NOS neurons contain erbB4 protein. We propose that the survival of NOS neuron in the hippocampus after injection of KA is associated with expression of erbB4, neuregulin receptor.
Adult ; Animals ; Brain ; Cell Proliferation ; Dentate Gyrus ; Endothelial Cells ; Epilepsy ; Hippocampus* ; Humans ; Immunohistochemistry ; Intercellular Signaling Peptides and Proteins ; Kainic Acid ; Muscle Cells ; Neuroglia ; Neurons ; Nitric Oxide Synthase* ; Nitric Oxide* ; Oligodendroglia ; Peripheral Nerves ; Rats* ; Schwann Cells ; Seizures*