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31.
Yang Hee Lee Ihn Rhan Lee Won Sick Won Chung Hee Park 《Archives of pharmacal research》1988,11(3):247-249
32.
Growth factor-dependent activation of the MAPK pathway in human pancreatic cancer: MEK/ERK and p38 MAP kinase interaction in uPA synthesis 总被引:3,自引:0,他引:3
Increased expression of the hepatocyte growth factor (HGF) receptor (c-met) and urokinase type plasminogen (uPA) correlated
with the development and metastasis of cancers. To investigate the role of HGF/c-met signaling on metastasis in cancer cells
stimulated with HGF, we examined the effects of a specific MEK1 inhibitor (PD98059) and a p38 MAP kinase inhibitor (SB203580)
on HGF-induced uPA expression in pancreatic cancer cell lines, L3.6PL and IMIM-PC2. Pretreatment of PD98059 decreased HGF-mediated
phosphorylation of extracellular receptor kinase (ERK), uPA secretion and expression of matrix metalloproteinases (MMP-2 and
MMP-9) in a dose-dependent manner. In contrast, SB203580 pretreatment increased HGF-stimulated ERK phosphorylation, uPA secretion
and expression of MMPs. SB203580 also reversed the inhibition of HGF-mediated ERK activation and uPA secretion in the PD98059-pretreated
cells. These results suggest that ERK activation by HGF might play important roles in the metastasis of pancreatic cancer
and the p38 MAPK pathway also involved in the HGF-mediated uPA secretion and metastasis by regulation of ERK pathway.
This revised version was published online in July 2006 with corrections to the Cover Date. 相似文献
33.
The application of molecular techniques to solid tumors 总被引:1,自引:0,他引:1
Recent developments in the field of molecular biology including the sequencing of the human genome and related high throughput methodologies are presenting the diagnostic pathologist with new opportunities to expand our understanding of human disease. These techniques enable the comprehensive assessment of molecular alterations with cell populations of interest, including cancer. It will be necessary for the diagnostic pathologist to become familiar with these techniques to effectively translate their potential into the clinical environment. 相似文献
34.
Detection of YMDD motif mutants by oligonucleotide chips in lamivudine-untreated patients with chronic hepatitis B virus infection 总被引:9,自引:0,他引:9
Heo J Cho M Kim HH Shin YM Jang HJ Park HK Kim CM Kim GH Kang DH Song GA Yang US 《Journal of Korean medical science》2004,19(4):541-546
Lamivudine, a nucleoside analogue, has been used widely as an effective antiviral agent for the treatment of patients with chronic hepatitis B virus (HBV) infection. However, the YMDD motif mutation of HBV polymerase resistant to lamivudine occurs very frequently after long term therapy. We developed an oligonucleotide chip for the detection of YMDD motif mutants resistant to lamivudine and investigated the prevalence of the mutants in patients with chronic HBV infection who had not been treated by lamivudine before. Forty patients who had not been treated with lamivudine were included in this study. Serum samples were tested by the oligonucleotide chips designed for detection of wild-type YMDD motif, M552V and M552I. Samples were confirmed by restriction fragment length polymorphism (RFLP) and direct sequencing. M552I mutants were detected by the oligonucleotide chips in 7.5% (3/40) of chronic HBV infected patients (2 chronic hepatitis and 1 cirrhosis). The results were in accordance with those of RFLP. YMDD motif mutants occur as natural genome variabilities in patients with chronic HBV infection who had not been treated with lamivudine before. Oligonucleotide chip technology is a reliable and useful diagnostic tool for the detection of mutants resistant to antiviral therapy in chronic HBV infection. 相似文献
35.
Sun Hee Choi Do Kyun Kim Young Yoo Jinho Yu Young Yull Koh 《Annals of allergy, asthma & immunology》2007,98(2):128-133
BACKGROUND: In asthmatic individuals, airway sensitivity and maximal airway response are increased. Airway sensitivity is usually evaluated by measuring the provocation concentration of inhaled methacholine or histamine that causes a decrease in forced expiratory volume in 1 second of 20% (PC20). The percentage decrease in forced vital capacity at the PC20 (deltaFVC) has been proposed as a surrogate marker for maximal airway response. Individuals with allergic rhinitis and no clinical evidence of asthma frequently exhibit airway hypersensitivity. OBJECTIVE: To compare the deltaFVC between patients with allergic rhinitis and mild asthmatic patients with a similar degree of airway hypersensitivity. METHODS: A retrospective analysis of methacholine challenge test data from 72 children with allergic rhinitis and airway hypersensitivity (methacholine PC20 < 16 mg/mL) (rhinitis group) and from 72 children with mild atopic asthma matched to the rhinitis group regarding the methacholine PC20 (asthma group). The deltaFVC was calculated on the concentration-response curve to methacholine. RESULTS: The mean +/- SD deltaFVC was significantly lower in the rhinitis group (15.0% +/- 3.6%) vs the asthma group (17.4% +/- 5.3%) (P = .002). There was no significant correlation between the deltaFVC and PC20 in the rhinitis (r = -0.101; P = .41) and asthma (r = -0.023; P = .85) groups when 2 patients with PC20 less than 1 mg/mL were excluded from each group. CONCLUSIONS: Patients with allergic rhinitis and airway hypersensitivity had a significantly lower deltaFVC than methacholine PC20-matched mild asthmatic patients, suggesting that the level of maximal airway response in patients with allergic rhinitis is lower than that in mild asthmatic patients with a similar degree of airway hypersensitivity. 相似文献
36.
In-Suk Kim Eun Sil Park Jae Young Lim Chang-Seok Ki Hyun Sook Chi 《Journal of Korean medical science》2008,23(6):1105-1108
Although acquired mutations in the GATA1 gene have been reported for Down syndrome-related acute megakaryoblastic leukemia (DS-AMKL) in Caucasians, this is the first report of a Korean Down syndrome patient with AMKL carrying a novel mutation of the GATA1 gene. A 3-yr-old Korean girl with Down syndrome was admitted to our hospital complaining of pallor and fever. The findings of a peripheral blood smear and bone marrow study were compatible with the presence of AMKL. A chromosome study showed 48,XX,-7,+21c,+21,+r[3]/47,XX,+21c[17]. Following GATA1 gene mutation analysis, a novel mutation, c.145dupG (p.Ala49GlyfsX18), was identified in the N-terminal activation domain of the GATA1 gene. This mutation caused a premature termination at codon 67 and expression of an abnormal GATA-1 protein with a defective N-terminal activation domain, and the absence of full-length GATA-1 protein. This case demonstrates that a leukemogenic mechanism for DS-AMKL is contributed by a unique collaboration between overexpressed genes from trisomy 21 and an acquired GATA1 mutation previously seen in Caucasians and now in a Korean patient. 相似文献
37.
Sun Hee Na Seung-Hyun Jin Soo Yong Kim 《International journal of psychophysiology》2006,62(2):238-242
Sleep deprivation can affect the waking electroencephalogram (EEG) that may reflect functional organization of the brain. We examined the effect of total sleep deprivation (TSD) on functional organization between different cortical areas from the waking EEG. Waking EEG data were recorded from 18 healthy male volunteers with eyes closed after 8-h night's sleep and after 24 h of TSD. The averaged cross mutual information (A-CMI) after 24 h of TSD were compared to before TSD. 24 h of TSD yielded the decreased A-CMIs in the inter-hemispheric C3-F4, C3-F8, and C3-C4 pairs: therefore, the electrodes that contribute to pairs with significant decrease of A-CMI were C3, F4, F8, and C4. The decreased A-CMIs between C3 and right frontal and central brain areas after 24 h of TSD may reflect the changes of cortico-cortical functional organization by homeostatic process during TSD. Our results of the frontal-area-related A-CMI decreases may support that the frontal brain regions are related to the homeostatic deterioration of brain function due to TSD. 相似文献
38.
Kim HK Jin SY Lee NS Won JH Park HS Yang WI 《Archives of pathology & laboratory medicine》2004,128(8):e96-e99
An anaplastic large cell lymphoma that was negative for Epstein-Barr virus and positive for Ki-1 (CD30) presented as a polypoid scalp mass in a 56-year-old man 16 years after renal transplantation. The lymphoma was of the CD4+ cytotoxic T-cell lineage, and the tumor cells also expressed CD56. Despite reduction in the dose of immunosuppression and localized radiotherapy, the tumor had rapidly progressed to involve the soft tissue of the right hand. Systemic chemotherapy induced complete regression of the soft tissue lesion. This case illustrates that posttransplant primary cutaneous CD30+ anaplastic large cell lymphomas may assume an aggressive clinical course but can still be controlled by systemic chemotherapy. 相似文献
39.
Fibroblast growth factor 2 induces differentiation and apoptosis of Askin tumour cells 总被引:7,自引:0,他引:7
Kim MS Kim CJ Jung HS Seo MR Juhnn YS Shin HY Ahn HS Thiele CJ Chi JG 《The Journal of pathology》2004,202(1):103-112
Peripheral primitive neuroectodermal tumour (PNET)/Ewing's sarcoma (ES) and neuroblastoma (NB) are related tumours of neural crest origin with primitive neural characteristics. Fibroblast growth factor 2 (FGF2) is a critical signalling molecule for primitive neural crest cells. The treatment of NB cells with FGF2 variably affects biological characteristics such as growth and differentiation, while in PNET/ES, FGF2 predominantly induces apoptosis. The JK-GMS Askin tumour cell line can be induced to differentiate upon treatment with nerve growth factor (NGF), indicating the integrity of the cellular machinery necessary for differentiation. The present study assesses whether FGF2 can induce differentiation in JK-GMS cells. JK-GMS cells expressed high-affinity FGF receptors (FGFRs), and treatment with FGF2 induced phosphorylation of FGFR1 together with activation of extracellular signal-regulated kinases (ERK1/ERK2) and c-Jun N-terminal kinase (JNK). Subsequent biological effects were growth inhibition, neuronal differentiation, and apoptosis, and these changes were associated with increased expression of neurofilaments, reduction of c-myc and bcl-2 expression, and activation of caspase 3. Treatment of the cells with a specific inhibitor of the MAPK/extracellular signal-regulated kinase (MEK)-1, PD98059, predominantly inhibited the effects of FGF2 on growth, differentiation, and apoptosis, while an inhibitor of JNK reduced apoptosis, indicating that the ERK1/2 and JNK pathways are critical components of FGF2-mediated effects in JK-GMS cells. Additional comparative analyses of FGF2-mediated effects in two ES cell lines (CADO-ES, RD-ES) and a PNET cell line (SK-N-MC) showed pronounced differentiation in SK-N-MC, but not in CADO-ES or RD-ES cells. This study demonstrates that FGF2 can induce neuronal differentiation of PNET including Askin tumour. These findings clearly indicate that the FGF2-mediated signalling pathway plays a critical role in controlling the major properties of PNET cells and may provide a potential therapeutic target for PNET. 相似文献
40.
Methods for derivation of human embryonic stem cells 总被引:6,自引:0,他引:6
Kim HS Oh SK Park YB Ahn HJ Sung KC Kang MJ Lee LA Suh CS Kim SH Kim DW Moon SY 《Stem cells (Dayton, Ohio)》2005,23(9):1228-1233
The expanded blastocysts, developed from 2PN-stage embryos, are generally divided into three categories: a good blastocyst containing a large and distinguishable inner cell mass (ICM), a blastocyst with a small and distinct ICM, and a blastocyst with a poorly defined ICM. In this study, we introduce methods for the derivation of human embryonic stem cells (hESCs) depending on the quality of the blastocysts. An immunosurgical method was used for the good expanded blastocysts. This method, however, raises the probability of ICM loss in cases of hESC derivation from blastocysts with smaller or indistinct ICMs. Furthermore, this method is also associated with a risk of the contamination of the hESCs with animal pathogens. To overcome these shortcomings, the partial- or whole-embryo culture method was used. For blastocysts with no visible ICM, the whole-embryo culture method was used to establish hESCs via the seeding of the entire blastocyst without its zona pellucida directly on a STO feeder layer. However, trophectodermal overgrowth tends to hinder the expansion of the ICM during the initial steps of hESC derivation. Therefore, the partial-embryo culture method was developed to establish hESCs from blastocysts with smaller ICMs. The surgical isolation of the region containing the ICM with an ultra-fine glass pipette alleviates trophectoderm overgrowth. This method is also applicable to blastocysts with large and distinct ICMs, and the efficiency of this method is comparable to that of the immunosurgical method. 相似文献