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101.
Akt/PKB activation in gastric carcinomas correlates with clinicopathologic variables and prognosis 总被引:23,自引:0,他引:23
Nam SY Lee HS Jung GA Choi J Cho SJ Kim MK Kim WH Lee BL 《APMIS : acta pathologica, microbiologica, et immunologica Scandinavica》2003,111(12):1105-1113
Akt/protein kinase B (PKB) plays an important role in cell survival. However, the role of Akt in the biology of gastric cancer has not been well studied. We sought to investigate the expression of Akt or phosphorylated Akt (pAkt) in human gastric carcinomas and to analyze the relationship between Akt or pAkt and the clinicopathologic parameters. The expressions of Akt and pAkt were evaluated immunohistochemically in 311 gastric carcinomas using the tissue array method. Akt expression was detected in 74% of the tumors and pAkt expression in 78%. pAkt was highly expressed in the early stage of pTNM (p=0.011). We also found an inverse association between pAkt and lymphatic invasion (p=0.01) or lymph node metastasis (p=0.008). pAkt expression was significantly correlated with a higher survival in patients with stage I carcinomas (p=0.0003). Interestingly, combined evaluation revealed that the group with pAkt-positive and lymph node-negative carcinomas showed a better prognosis than the other groups (p<0.0001). In addition, pAkt was shown to correlate positively with APC (p=0.002) and Smad4 (p<0.0001) expression. These findings suggest that pAkt expression may help to predict the clinical outcome of gastric cancer patients. 相似文献
102.
Behavioral characteristics of a mouse model of cancer pain 总被引:5,自引:0,他引:5
Pain is a major symptom in cancer patients, and most cancer patients with advanced or terminal cancers suffer from chronic pain related to treatment failure and/or tumor progression. In the present study, we examined the development of cancer pain in mice. Murine hepatocarcinoma cells, HCa-1, were inoculated unilaterally into the thigh or the dorsum of the foot of male C3H/HeJ mice. Four weeks after inoculation, behavioral signs were observed for mechanical allodynia, cold allodynia, and hyperalgesia using a von Frey filament, acetone, and radiant heat, respectively. Bone invasion by the tumor commenced from 7 days after inoculation of tumor cells and was evident from 14 days after inoculation. Cold allodynia but neither mechanical allodynia nor hyperalgesia was observed in mice that received an inoculation into the thigh. On the contrary, mechanical allodynia and cold allodynia, but not hyperalgesia, were developed in mice with an inoculation into the foot. Sometimes, mirror-image pain was developed in these animals. These results suggest that carcinoma cells injected into the foot of mice may develop severe chronic pain related to cancer. This animal model of pain would be useful to elucidate the mechanisms of cancer pain in humans. 相似文献
103.
Metabolite identification and urinary and biliary excretion of the new fluoroquinolone antibacterial agent DW116 [1-(5-fluoro-2-pyridyl)-6-fluoro-7-(4-methyl-1-piperazinyl)-1,4-dihydro-4-oxoquinoline-3-carboxylic
acid, hydrochloride] after oral administration have been studied in Sprague-Dawley rats. The excretion kinetics were monoexponential.
Most of the drug was eliminated via the hepatic and renal routes. Mean renal clearance of DW116 was 73.4 ml/hr/kg and mean
biliary clearance was 83.8 ml/hr/kg. The major metabolite excreted in the bile was identified as the glucuronide ester of
the parent drug using base-hydrolysis of the conjugate metabolite followed by co-HPLC with standard compound,19F-NMR and LC-MS methods. The glucuronide conjugate was also found in urine. The mean urinary recoveries of free and total
(free plus glucuronide ester) DW116 were 28.6±2.7% and 36.4±1.8% of the administered dose and the corresponding biliary recoveries
were 14.4±5.5% and 37.0±7.6%, respectively. 相似文献
104.
105.
- Recently, 4-chloro-3-ethyl phenol (CEP) has been shown to cause the release of internally stored Ca2+, apparently through ryanodine-sensitive Ca2+ channels, in fractionated skeletal muscle terminal cisternae and in a variety of non-excitable cell types. Its action on smooth muscle is unknown. In this study, we characterized the actions of CEP on vascular contraction in endothelium-denuded dog mesenteric artery. We also determined its ability to release Ca2+, by use of Ca2+ imaging techniques, on dog isolated mesenteric artery smooth muscle cells and on bovine cultured pulmonary artery endothelial cells.
- After phenylephrine-(PE, 10 μM) sensitive Ca2+ stores were depleted by maximal PE stimulation in Ca2+-free medium, the action of CEP on refilling of the emptied PE stores was tested, by first pre-incubating the endothelium-denuded artery in CEP for 15 min before Ca2+ was restored for a 30 min refilling period. At the end of this period, Ca2+ and CEP were removed, and the arterial ring was tested again with PE to assess the degree of refilling of the internal Ca2+ store.
- In a concentration-dependent manner (30, 100 and 300 μM), CEP significantly reduced the size of the post-refilling PE contraction (49.4, 28.9 and 5.7% of control, respectively) in Ca2+-free media. This suggests that Ca2+ levels are reduced in the internal stores by CEP treatment. CEP alone did not cause any contraction either in Ca2+-containing or Ca2+-free Krebs solution.
- Restoring Ca2+ in the presence of PE caused a large contraction, which reflects PE-induced influx of extracellular Ca2+. The contraction of tissues pretreated with 300 μM CEP was significantly less compared with controls. However, tissues pretreated with 30 and 100 μM CEP were unaffected. Washout of CEP over 30 min produced complete recovery of responses to PE in Ca2+-free and Ca2+-containing medium suggesting a rapid reversal of CEP effects.
- Concentration-response curves were constructed for PE, 5-hydroxytryptamine (5-HT) and K+ in the absence of and after 30 min pre-incubation with 30, 100 and 300 μM CEP. In all cases, CEP caused a concentration-dependent depression of the maximum response to PE (84.8, 43.4 and 11.6% of control), 5-HT (65.4, 25.7 and 6.9% of control) and K+ (77.6, 41.1 and 10.8% of control).
- Some arterial rings were pre-incubated with ryanodine (30 μM) for 30 min before the construction of PE concentration-response curves. In Ca2+-free Krebs solution, ryanodine alone did not cause any contraction. However, 58% (11 out of 19) of the tissues tested with ryanodine developed contraction (6.9±1.2% of 100 mM K+ contraction, n=11) in the presence of external Ca2+. EC50 values for PE in ryanodine-treated tissues (1.7±0.25 μM, n=16) were not significantly different from controls (2.5±0.41 μM, n=22). Maximum contractions to PE (118.5±4.4% of 100 mM K+ contraction, n=16) were also unaffected by ryanodine when compared to controls (129±4.2%, n=23).
- When fura-2 loaded smooth muscle cells (n=13) and endothelial cells (n=27) were imaged for Ca2+ distribution, it was observed that 100 and 300 μM CEP in Ca2+-free medium caused Ca2+ release in both cell types. Smooth muscle cells showed a small decrease in cell length. Addition of EGTA (5 mM) reversed the effect of CEP on intracellular Ca2+ to control values.
- These data show, for the first time in vascular smooth muscle and endothelial cells, that CEP releases Ca2+ more rapidly than ryanodine. Unlike ryanodine, CEP caused no basal contraction but depressed contractions to PE, 5-HT and K+. The lack of basal contraction may result from altered responsiveness of the contractile system to intracellular Ca2+ elevation.
106.
Hwan Bae Lee Jong Hwan Kwak Ok Pyo Zee Seung Jo Yoo 《Archives of pharmacal research》1994,17(4):273-277
Six flavonoids were isolated from the aerial parts ofCirsium rhinoceros. The flavonoids were identified as apigenin, luteolin, pectolinarigenin-7-O-β-D-glucopyranoside, linarin, pectolinarin and hispidulin-7-O-α-L-rhamnopyranosyl-(1→2)-β-D-glucopyranoside on the basis of chemical and spectral evidence. 相似文献
107.
Sapin PM Kwan OL Xie GY Smith MD DeMaria AN 《Echocardiography (Mount Kisco, N.Y.)》1995,12(6):559-569
An echocardiographic system has been developed that performs automatic endocardial border detection and instantaneously calculates and displays a waveform of left ventricular cavity area versus time. The purpose of this study was to compare measurements of left ventricular filling dynamics from automatic border detection echocardiography with similar measurements from cineventriculography. Thirty-three patients undergoing cardiac catheterization had automatic border detection echocardiography performed within 45 minutes of cineventriculography. Ten patients had normal catheterization findings and 23 had cardiac disease. The automatic border detection waveforms generated from two echocardiographic views were measured to determine the fraction of filling occurring during the early diastolic rapid filling phase and during the filling phase resulting from atrial contraction. Similar fractions were derived from curves generated from frame-by-frame measurements of cineangiographic volumes. Results were analyzed by correlating echocardiographic and cineventriculographic results, and by a limits of agreement analysis (limits of agreement were +/- 2 standard deviations of the mean difference between echocardiography and cineventriculography). There were significant correlations between echocardiography and cineventriculography for each of the parameters studied. The best results were obtained for the apical four-chamber view (rapid filling fraction r = 0.72, P < 0.0001, atrial filling fraction r = 0.56, P < 0.001). Differences in filling patterns between normal and abnormal patient groups detected by cineventriculography were also detected by automatic border detection echocardiography. However, broad limits of agreement were observed, that may limit the ability of the automatic border detection system to reliably predict cineventriculographic results in an individual patient. Automatic border detection echocardiography can provide information about left ventricular filling dynamics that is similar to that obtained from frame-by-frame analysis of cineventriculograms. However, the variability in the results may limit the application of the technique in individual patients. 相似文献
108.
Background: this study was designed to characterize some of the biochemical and molecular genetic changes during reversion
of human fat cells. Methods: mature adipocytes were isolated from greater omental fat tissue of eight lean and 14 massively
obese persons by established methodology. Results: at day 7 of adherence to Leighton tubes, there was appreciable depletion
of triacylglycerol, as well as assumption of an elongated contour. Relatedly, there was an increase in the expression of β-actin
mRNA and a significant decrease in the specific activity of cytosolic glycerophosphate dehydrogenase. The decrement in the
specific activity of glycerophosphate dehydrogenase, after 7 days in culture, was significant at p < 0.001. Basic fibroblast growth factor at 10 ngml-1 accelerated significantly (p < 0.03) the decrease in the specific activity of glycerophosphate dehydrogenase in adipose cells from lean subjects. In contrast,
basic fibroblast growth factor had no significant influence on cells from massively obese persons. Conclusion: such resistance
may contribute to the intractability of massive obesity. 相似文献
109.
110.