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81.
Leo Jeng Alexandra V Yamshchikov Suzanne E Judd Henry M Blumberg Gregory S Martin Thomas R Ziegler Vin Tangpricha 《Journal of translational medicine》2009,7(1):28
Background
Vitamin D insufficiency is common in hospitalized patients. Recent evidence suggests that vitamin D may enhance the innate immune response by induction of cathelicidin (LL-37), an endogenous antimicrobial peptide produced by macrophages and neutrophils. Thus, the relationship between vitamin D status and LL-37 production may be of importance for host immunity, but little data is available on this subject, especially in the setting of human sepsis syndrome and other critical illness. 相似文献82.
Chiu‐Chun Lin Mei‐Chi Chang Hsiao‐Hua Chang Tong‐Mei Wang Wan‐Yu Tseng Tseng‐Fang Tai Hung‐Wei Yeh Ting‐Ting Yang Liang‐Jiunn Hahn Jiiang‐Huei Jeng 《Environmental and molecular mutagenesis》2009,50(5):367-374
Epidemiological studies have shown a strong association between environmental exposure to betel quid (BQ) and oral cancer. Areca nut (AN), an ingredient of BQ, contains genotoxic and mutagenic compounds. In this study, we found that AN extract (ANE) inhibited the growth of Chinese hamster ovary cells (CHO‐K1) in a dose‐ and time‐dependent manner. Intracellular reactive oxygen species (ROS) levels and micronuclei (MN) frequency were significantly increased following ANE treatment in CHO‐K1 cells. Addition of catalase markedly inhibited ANE‐induced MN formation, indicating that ANE‐induced genotoxicity was correlated with intracellular H2O2. Incubation of CHO‐K1 cells with ANE (400–800 μg/ml) for 24 hr caused G2/M arrest, and prolonged exposure to ANE (800 μg/ml) significantly induced cell death. Surprisingly, ANE itself caused cytokinesis failure and subsequent increase in binucleated cell formation. Coexposure to catalase (2,000 U/ml) and ANE (800 μg/ml) reduced the generation of binucleated cells, indicating that ANE‐induced cytokinesis failure was associated with oxidative stress. Following prolonged exposure to ANE, an accumulation of hyperploid/aneuploid cells concomitant with bi‐, micro‐ or multinucleated cells was found. In summary, our results demonstrate that ANE exposure to CHO‐K1 cells caused increased MN frequency, G2/M arrest, cytokinesis failure, and an accumulation of hyperploid/aneuploid cells. These events are associated with an increase in intracellular H2O2 level and actin filament disorganization. Environ. Mol. Mutagen., 2009. © 2009 Wiley‐Liss, Inc. 相似文献
83.
Chao‐Chuan Chi Chorng‐Chih Huang Jau‐Min Chien Sau‐Tung Chu Wei‐Chuan Chen Hong‐Tai Chang Ko‐Long Lin Jeng‐Yu Tsai Wei‐Chuan Liao Chiang‐Ting Chou Chung‐Ren Jan 《Drug development research》2008,69(8):508-513
The effect of BayK 8644, a chemical widely used to activate L‐type Ca2+ channels, on cytosolic free Ca2+ concentrations ([Ca2+]i) in human oral cancer cells (OC2) has not been explored to date. The present study examined whether BayK 8644 altered basal [Ca2+]i levels in suspended OC2 cells by using fura‐2. BayK 8644 (10 pM–10 µM) increased [Ca2+]i in a concentration‐dependent manner. The Ca2+ signal was reduced partly by removing extracellular Ca2+. BayK 8644‐induced Ca2+ influx was blocked by nifedipine, but was not altered by the store‐operated Ca2+ entry inhibitors, econazole and SKF96365; protein kinase C modulators phorbol 12‐myristate 13‐acetate (PMA) and GF109203X; the protein kinase A inhibitor H89; and the phospholipase A2 inhibitor, aristolochic acid. In Ca2+‐free medium, after pretreatment with 1 µM BayK 8644, 1 µM thapsigargin (an endoplasmic reticulum Ca2+ pump inhibitor)‐induced [Ca2+]i rises were abolished; and conversely, thapsigargin pretreatment abolished BayK 8644‐induced [Ca2+]i rises. Inhibition of phospholipase C with U73122 did not change BayK 8644‐induced [Ca2+]i rises. Collectively, in OC2 cells, BayK 8644 induced [Ca2+]i rises by causing phospholipase C‐independent Ca2+ release from the endoplasmic reticulum; and Ca2+ influx via L‐type Ca2+ channels. Drug Dev Res 69: 2008. © 2008 Wiley‐Liss, Inc. 相似文献
84.
J. F. Tsai J. E. Jeng M. S. Ho W. Y. Chang M. Y. Hsieh Z. Y. Lin J. H. Tsai 《British journal of cancer》1996,73(12):1498-1502
To assess the role of hepatitis B e antigen (HBeAg) and its interaction with hepatitis B surface antigen (HBsAg) on the development of hepatocellular carcinoma (HCC), this case-control study included 361 age- and sex-matched pairs of patients with histologically proven HCC and healthy control subjects. HBsAg, HBeAg and antibody to HBeAg (anti-HBe) were detected by radioimmunoassay. Antibodies to hepatitis C virus (anti-HCV) were detected by second-generation enzyme immunoassay. The prevalences of HBeAg (20.2%), HBsAg (80.3%) and anti-HCV (29.5%) in cases were higher than in controls (1.9%, 20.7%, and 2.7% respectively; each P < 0.0001). Using patients negative for HBsAg, HBeAg and anti-HBe as a referent group, univariate analysis indicated that HBsAg alone or HBsAg and HBeAg were risk factors for HCC (P for trend < 0.0001). Calculation of incremental odds ratio indicated that there was additive interaction between HBsAg and HBeAg. Multivariate analysis indicated that HCC development was strongly associated with the presence of HBeAg (odds ratio, 8.1; 95% confidence interval, 2.4-27.1), HBsAg (odds ratio, 68.4; 95% confidence interval, 20.5-227.8) and anti-HCV (odds ratio, 59.3; 95% confidence interval, 13.6-258.4). In conclusion, HBsAg, HBeAg and anti-HCV are independent risk factors for HCC. There is additive and independent effect modification between HBsAg and HBeAg on the development of HCC. 相似文献
85.
Pedunculated Hepatocellular Carcinoma: Clinicopathologic Study of 18 Surgically Resected Cases 总被引:9,自引:0,他引:9
We present the clinical features and outcomes of 18 surgically treated pedunculated hepatocellular carcinomas (P-HCCs). Hepatocellular
carcinoma is a notorious, hyperendemic disease in Taiwan. Pedunculated HCC, although not a novel finding, has been recognized
and diagnosed early by various imaging modalities. However, the clinicopathologic picture has not been fully clarified, and
the prognosis varies in each report. From 1986 to 1998 the clinical features of 18 surgically treated cases of P-HCC were
reviewed, including demographics, laboratory data, operative findings, pathologic features, and follow-up results. Factors
that may influence the outcomes were also analyzed. Clinical features and outcomes of 414 patients with nonpedunculated hepatocellular
(HCC) were summarized for comparison. Of 432 surgical resected hepatocellular carcinomas, 18 (4.2%) were P-HCCs. Larger tumor
size, more capsule formation, less vascular invasion, and wider resection margins were significantly prominent in the patients
in P-HCC group compared with those in the NP-HCC group. Multivariate stepwise logistic regression analysis revealed that the
P-HCC group had significantly larger tumors and wider resection margins. The 1-, 3-, and 5-year survival rates of P-HCC patients
were 88.3%, 77.4%, and 45.6%, respectively. A significant difference in survival was found between the P-HCC and NP-HCC groups.
P-HCC patients without vascular invasion might have a significantly better survival demonstrated by log-rank analysis stratified
by capsular invasion, vascular invasion, resection, and tumor size. We present the clinical features and outcomes of 18 surgically
treated pedunculated HCCs. Pedunculated HCCs might have a better survival than conventional HCCs after hepatic resection,
especially if there is no vascular invasion. 相似文献
86.
Loh SH Tsai CS Tsai Y Chen WH Hong GJ Wei J Cheng TH Lin CI 《European journal of pharmacology》2002,443(1-3):169-177
Accumulation of oxygen free radicals is an important mediator of post-ischemia/reperfusion cardiac dysfunction. However, oxidative injury has not been well characterized in human cardiac tissues. In the present study, we superfused hydrogen peroxide (H(2)O(2)) into the diseased human ventricle in order to assess the effects of oxygen free radicals on the electromechanical parameters and the intracellular pH (pH(i)), and to test the ability of certain potential cardioprotective agents, including scavengers of hydrogen peroxide (dibenzamidostilbene disulfonic acid; DBDS), the.OH free radical (N-(mercaptopropionyl)-glycine; N-MPG), and the HOCl free radical (L-methionine), to protect against oxidative injury. Disease human ventricular tissues were obtained from patients undergoing heart transplantation. Electrophysiological experiments were performed using a traditional micropipette, while the pH(i) was measured by microspectrofluorimetry. We found that (a) H(2)O(2) (30 microM-3 mM) induced a significant dose-dependent intracellular acidosis, (b) H(2)O(2) (30 microM-3 mM) had a notable dose-dependent biphasic effect on the contractile force (an increase, followed by a decrease), while moderate concentrations of H(2)O(2) also inhibited the generation of action potential and increased the diastolic resting force significantly, and (c) N-MPG caused significant block of both the intracellular acidosis and the electromechanical inhibition induced by 3 mM H(2)O(2), whereas L-methionine and DBDS did not. Our data suggest that the toxic effects of H(2)O(2) are caused mainly through the generation of.OH, which is attributed to the intracellular acidosis seen in the diseased human ventricle. 相似文献
87.
Spontaneous tumour rupture and prognosis in patients with hepatocellular carcinoma 总被引:17,自引:0,他引:17
BACKGROUND: Hepatocellular carcinoma (HCC) is a common disease in Taiwan. Ruptured HCC is an uncommon and potentially fatal complication of the condition. Information on the impact of ruptured HCC on hepatic resection is, however, limited. METHODS: The clinical features of 60 patients with ruptured HCC who underwent hepatic resection from 1986 to 1998 were reviewed. Clinical features and factors influencing the outcome of 475 patients with non-ruptured HCC were used for comparison. RESULTS: Of 535 surgically resected HCCs, 60 (11.2 per cent) were ruptured. Univariate analysis showed that sudden onset of abdominal pain, physical signs of haemodynamic unstability, reduced haemoglobin level and a raised aspartate aminotransferase level were more frequently found in patients with ruptured HCC than in those with non-ruptured tumours. Multivariate stepwise logistic regression analysis revealed sudden-onset abdominal pain to be the only independently significant factor in patients in the ruptured HCC group. The 1-, 3- and 5-year survival rates of patients with non-ruptured HCC were 72.1, 47.3 and 33.9 per cent, and those of patients with ruptured HCC were 54.2, 35.0 and 21.2 per cent respectively. Similar overall survival rates were found in patients with ruptured and non-ruptured HCC, although patients in the non-ruptured HCC group had a significantly better disease-free survival rate (P = 0.023). CONCLUSION: The presence of sudden-onset abdominal pain is the only independent indicator of ruptured HCC. Hepatic resection, when feasible, is the treatment of choice and can result in an overall survival rate comparable to that of patients with non-ruptured HCC. 相似文献
88.
89.
Silymarin protects dopaminergic neurons against lipopolysaccharide-induced neurotoxicity by inhibiting microglia activation 总被引:10,自引:0,他引:10
Wang MJ Lin WW Chen HL Chang YH Ou HC Kuo JS Hong JS Jeng KC 《The European journal of neuroscience》2002,16(11):2103-2112
An inflammatory response in the central nervous system mediated by activation of microglia is a key event in the early stages of the development of neurodegenerative diseases. Silymarin is a polyphenolic flavanoid derived from milk thistle that has anti-inflammatory, cytoprotective and anticarcinogenic effects. In this study, we first investigated the neuroprotective effect of silymarin against lipopolysaccharide (LPS)-induced neurotoxicity in mesencephalic mixed neuron-glia cultures. The results showed that silymarin significantly inhibited the LPS-induced activation of microglia and the production of inflammatory mediators, such as tumour necrosis factor-alpha and nitric oxide (NO), and reduced the damage to dopaminergic neurons. Therefore, the inhibitory mechanisms of silymarin on microglia activation were studied further. The production of inducible nitric oxide synthase (iNOS) was studied in LPS-stimulated BV-2 cells as a model of microglia activation. Silymarin significantly reduced the LPS-induced nitrite, iNOS mRNA and protein levels in a dose-dependent manner. Moreover, LPS could induce the activation of p38 mitogen-activated protein kinase (MAPK) and c-jun N-terminal kinase but not extracellular signal-regulated kinase. The LPS-induced production of NO was inhibited by the selective p38 MAPK inhibitor SB203580. These results indicated that the p38 MAPK signalling pathway was involved in the LPS-induced NO production. However, the activation of p38 MAPK was not inhibited by silymarin. Nevertheless, silymarin could effectively reduce LPS-induced superoxide generation and nuclear factor kappaB (NF-kappaB) activation. It suggests that the inhibitory effect of silymarin on microglia activation is mediated through the inhibition of NF-kappaB activation. 相似文献
90.
Chromosome 8p21-22 is a frequent site of loss of heterozygosity in many types of cancer, including hepatocellular carcinoma (HCC). Tumor necrosis factor-related apoptosis-inducing ligand-receptor 2 (TRAIL-R2/DR5), a member of tumor necrosis factor receptor family, is mapped to chromosome 8p21-22. Mutations of TRAIL-R2 have been detected in lung cancer, breast cancer, head and neck cancer, and non-Hodgkin's lymphoma. In this study, we analyzed the entire coding regions and all splicing sites of TRAIL-R2 in 40 HCCs and the death domain region in additional 60 HCCs. We could detect one point mutation in the death domain in only one HCC (1%). Our data suggest that somatic mutations of TRAIL-R2 gene do not play an important role in the carcinogenesis of HCC. 相似文献