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991.
We elucidate the roles of various protein kinases involved in complement 5a (C5a)-induced cell migration. Results showed that extracellular signal-regulated kinase1/2 (ERK1/2), p38 mitogen-activated protein kinase (p38 MAPK) and phosphatidylinositol 3-kinase (P13K) were necessary for C5a-induced migration, whereas protein kinase C and c-Jun N-terminal kinase (JNK) were nonessential. C5a-induced migration was also suppresses by phospholipase C (PLC) inhibitor U73122 and pertussis toxin (PTX). We found that C5a-induced, time-dependent (1) ERK1/2 phosphorylation was markedly diminished by PTX, U73122, P13K inhibitors wortmannin and LY294002 and ERK1/2 inhibitor PD98059; (2) Akt phosphorylation was also attenuated by the above inhibitors except PD98059; (3) p38 MAPK phosphorylation was only affected by PTX. Furthermore, C5a also stimulated PLCbeta(2) membrane translocation in a time-dependent manner that occurred early prior to Akt phosphorylation and could be abolished only by PTX and U73122. These results suggest that C5a, through the activation of PTX-sensitive G protein, to differentially stimulate ERK1/2 and p38 MAPK phosphorylation and evoke cell migration. That is, ERK1/2 but not p38 MAPK phosphorylation is down stream of P13K/Akt and modulated by PLC. Additionally, beta(2) isoform may be one of the participates in C5a signal and acts more upstream of P13K/Akt. 相似文献
992.
Isolation of salicin derivatives from Homalium cochinchinensis and their antiviral activities 总被引:1,自引:0,他引:1
Ishikawa T Nishigaya K Takami K Uchikoshi H Chen IS Tsai IL 《Journal of natural products》2004,67(4):659-663
The chemical constituents of Homalium cochinchinensis were examined. From the root bark, in addition to the previously reported cochinolide and its beta-glucopyranoside, cochinchiside A (1) and tremulacinol (4) were isolated together with three known compounds [benzoic acid, tremulacin (2), and tremuloidin (3)]. From the leaves, cochinchiside B (5) was isolated as new compound. The structures of the new compounds (1, 4, 5) were determined by spectroscopic and/or chemical methods. Antiviral testing of compounds 2-5 against HSV-1 and HSV-2 showed that tremulacin (2) and cochinchiside B (5) were weakly active. Tremulacin (2) was also weakly active against HIV-1. 相似文献
993.
Chen YM Perng RP Shih JF Lee YC Lee CS Tsai CM Whang-Peng J 《British journal of cancer》2004,90(2):359-365
Cyclooxygenase-2 (COX-2) expression is increased in breast cancer and surgery has been shown to increase the growth of metastatic tumours. We investigated the effect of selective COX-2 inhibition on the growth of metastases in either an experimental metastasis model or following excision of a murine primary breast tumour. 50,000 4T1 mammary carcinoma cells were injected into the mammary fat pad of female BALB/c mice. When the mean TD reached 8+/-0.4 mm, tumours were excised and the mice were randomised into two groups (n=12 per group) to receive daily intraperitoneal injections of the selective COX-2 inhibitor, SC-236 or drug vehicle for 14 days. Alternatively, experimental metastases were established by tail-vein injection of 50,000 4T1 cells. Mice received either the selective COX-2 inhibitor, SC-236 or drug vehicle for 14 days (n=12 per group). SC-236 treatment significantly reduced tumour burden, the number and size of spontaneous metastases following primary tumour excision. SC-236 treatment also reduced tumour burden, the number and size of experimental metastases. Immunohistochemical staining demonstrated that COX-2 inhibition reduced microvessel density and increased apoptosis within both spontaneous and experimental metastases. These data clearly demonstrate that the selective COX-2 inhibitor, SC-236, has potent antimetastatic activity against both spontaneous metastases arising following primary tumour excision and experimental metastases. 相似文献
994.
Restaging of recurrent cervical carcinoma with dual-phase [18F]fluoro-2-deoxy-D-glucose positron emission tomography 总被引:3,自引:0,他引:3
Lai CH Huang KG See LC Yen TC Tsai CS Chang TC Chou HH Ng KK Hsueh S Hong JH 《Cancer》2004,100(3):544-552
BACKGROUND: The clinical value of positron emission tomography (PET) with [18F]fluoro-2-deoxy-D-glucose (FDG) for primary staging in cervical carcinoma appears to be promising. The authors sought to evaluate the diagnostic efficacy and benefit of PET in restaging cervical carcinoma at the time of first recurrence. METHODS: Forty patients with cervical carcinoma who experienced confirmed treatment failure but who were feasible candidates for curative salvage therapy were enrolled prospectively in the current study. Restaging was performed with PET and with computed tomography and/or magnetic resonance imaging (CT/MRI). Dual-phase PET was performed by adding 3-hour-delayed images to the 40-minute scans. The results of the PET and CT/MRI scans were compared. Lesion status was determined by pathologic findings or by clinical follow-up. The receiver operating characteristic curve method with calculation of area under the curve (AUC) was used to evaluate diagnostic efficacy. The primary endpoint was percent improvement in restaging (with improvement indicated by treatment modification) after PET. The secondary endpoint was 2-year overall survival among study participants compared with comparable previously treated patients who did not undergo disease restaging with PET. RESULTS: Twenty-two patients (55%) had their treatment modified due to PET findings. PET was significantly superior to CT/MRI (sensitivity: 92% vs. 60%; AUC: 0.962 vs. 0.771; P<0.0001) in identifying metastatic lesions. For individuals receiving primary surgery, a significantly better 2-year overall survival rate was observed among study participants compared with patients who underwent disease restaging without PET (HR, 0.21 [95% confidence interval, 0.05-0.83]; P=0.020). CONCLUSIONS: Dual-phase FDG-PET is superior to CT/MRI in the restaging of recurrent cervical carcinoma. Restaging with PET provides benefit by allowing the physician to offer optimal management of recurrent cervical carcinoma. 相似文献
995.
Synergy between anti-endoglin (CD105) monoclonal antibodies and TGF-beta in suppression of growth of human endothelial cells 总被引:10,自引:0,他引:10
She X Matsuno F Harada N Tsai H Seon BK 《International journal of cancer. Journal international du cancer》2004,108(2):251-257
Endoglin (CD105) is a proliferation-associated cell membrane antigen of endothelial cells and strongly expressed in the angiogenic vasculature of solid tumors. Endoglin is essential for angiogenesis/vascular development and an ancillary transforming growth factor beta (TGF-beta) receptor. Certain anti-endoglin monoclonal antibodies (mAbs), termed SN6 series mAbs, inhibited angiogenesis, tumor growth and metastasis in mice. We investigated the mechanisms by which anti-endoglin mAbs suppress growth of proliferating endothelial cells. We found that 4 SN6 series mAbs suppressed growth of human umbilical vein endothelial cells (HUVECs) in a dose-dependent manner in the absence of any effector cells or complement. Significant differences in the growth suppression between the 4 anti-endoglin mAbs defining different epitopes were observed. These differences were not determined by antigen-binding avidities of the mAbs. Combination of TGF-beta1 and each of the 4 anti-endoglin mAbs exerted synergistic growth suppression of HUVECs. Binding of anti-endoglin mAbs to endoglin-expressing cells did not block the subsequent binding of TGF-beta1. Conversely, preincubation of HUVECs with TGF-beta1 did not change cell surface expression of endoglin. The present results suggest that direct suppression of the endothelial cell growth by SN6 series mAbs is one of the underlying mechanisms by which anti-endoglin mAbs exert antiangiogenic and tumor-suppressive activity in vivo. The results further suggest that TGF-beta1 plays an important role in the in vivo antiangiogenic efficacy of anti-endoglin mAbs by synergistically enhancing the activity of these mAbs. Further studies of the present novel findings may provide valuable information about the functional roles of endoglin and anti-endoglin mAbs in the TGF-beta-mediated cell regulation. 相似文献
996.
997.
Chi HP Ho KY Chai CY Ta CF Wang LF Lee KW Kuo WR Wu SC Tsai SM 《The Kaohsiung journal of medical sciences》2004,20(1):6-11
Middle ear cholesteatoma is destructive to auditory ossicles and temporal bone, and treatment usually requires surgical removal of all epithelial content. Epidermal growth factor (EGF) can stimulate the growth and differentiation of a variety of mammalian cells, including epithelial cells. Our study used the avidin-biotin complex technique to evaluate the expression of EGF in 40 cases of middle ear cholesteatoma (active cholesteatoma, 31 cases; inactive cholesteatoma, 9 cases) and 34 normal postauricular skin samples. In middle ear cholesteatoma, EGF was expressed in squamous epithelium in 21 cases (53%), fibroblasts in two cases (5%), and cholesteatoma endothelium in two cases (5%). In normal postauricular skin, EGF was expressed in squamous epithelium in 14 samples (41%), fibroblasts in one sample (3%), and endothelium in none. No statistical difference in EGF expression was found between cholesteatoma and normal postauricular skin samples. These results show that the distribution of EGF in middle ear cholesteatoma is not deranged and that the progression of cholesteatoma might be induced by the release of factors from the cholesteatoma matrix via autocrine stimulation, or by inflammatory cells of the subepithelial tissue through paracrine stimulation, or in both of these ways. 相似文献
998.
Brain-derived neurotrophic factor (BDNF), a member of the nerve-growth-factor family, plays an important role in neuronal survival and development, and it can modulate serotonergic activity. Further, BDNF has been implicated in the expression of personality traits and in cognitive function. We tested the associations between functional BDNF Val66Met genetic variants, and personality trait and intelligence in a cohort of 114 healthy young Chinese females. Subjects with the Val/Val genotype had a significantly higher mean performance IQ than Val/Met carriers, especially for the Object Assembly subtest. No significant association was demonstrated for the BDNF polymorphism and any of the Tridimensional Personality Questionnaire personality-factor scores, including harm avoidance. These results suggest that genetic variants of the BDNF gene may play a role in specific cognitive functions, but not in overall intelligence. In contrast to a recent report, however, this polymorphism does not appear to be associated with the neuroticism-related personality trait. 相似文献
999.
Located on the presynaptic and postsynaptic terminals of serotonergic neurons, serotonin 1B receptors (5-HT1B) are involved in the modulation of serotonergic activity. The implications of 5-HT1B study of animal models of schizophrenia and antipsychotic activity involving defective sensory processes suggest that this receptor may be involved in the pathogenesis of schizophrenic disorders. In a population-based association study, we tested the hypothesis that the allelic variant, A-161T, of the 5-HT1B gene confers susceptibility to schizophrenic disorders and is associated with age of onset, aggressive behavior and attempted suicide. We genotyped the A-161T polymorphism in 110 patients with schizophrenic disorders and in 215 normal controls. No association was demonstrated between 5-HT1B genotype or allele frequencies and schizophrenic disorders, except for a trend for later age at disease onset in A/A homozygote schizophrenics in comparison with A/T heterozygote patients (p = 0.071). No significant difference in genotype distribution was determined comparing patients with and without aggressive behavior, and those with and without a history of suicide attempt. These findings suggest that the investigated 5-HT1B genetic polymorphism does not play a major role in the pathogenesis of schizophrenic disorders. 相似文献
1000.
Weight gain, a common adverse effect of clozapine, may impair health and affect patient compliance during treatment with this agent. The aim of this study was to investigate the relationship between genetic variants of the adrenergic beta3 receptor (ADRB3) and the G-protein beta3 subunit (GNB3) and clozapine-induced body weight change (BWC). Eighty-seven treatment-resistant schizophrenic patients were weighed before and after 4 months of clozapine treatment, with the subjects gaining an average of 2.6 kg in body weight. No statistically significant relationship was demonstrated for the investigated ADRB3 Trp64Arg and the GNB3 C825T polymorphisms in terms of BWC post-treatment, suggesting these two polymorphisms do not play a significant role in clozapine-induced BWC. Further exploration of other genetic variants implicated in clozapine-induced BWC is important, however, in order to predict and reduce clozapine-associated weight gain. 相似文献