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Wen-Ta Chiu Shing-Chuan Shen Jyh-Ming Chow Cheng-Wei Lin Ling-Tin Shia Yen-Chou Chen 《Neurobiology of disease》2010,37(1):118-129
In the presence of 12-O-tetradecanoylphorbol-13-acetate (TPA) stimulation, an increase in the migration/invasion of U87 glioblastoma cells was detected by a wound healing assay, transwell analysis, and spheroid formation assay by inducing matrix metalloproteinase-9 (MMP-9) enzyme activity via a gelatin zymographic analysis. A dose- and time-dependent increase in cyclooxygenase-2 (COX-2) gene expression with elevated prostaglandin E2 (PGE2) production was identified in TPA- but not in 4α-TPA (a respective inactive compound)-treated U87 cells TPA-induced migration/invasion was significantly blocked by adding the COX-2-specific inhibitor, NS398, through a reduction in PGE2 production. Data from the pharmacological studies using specific chemical inhibitors showed that activation of protein kinase C (PKC) and extracellular signal-regulated kinases (ERKs) was involved in TPA-induced migration/invasion, COX-2 protein expression, and MMP-9 activation. Stimulation of intracellular peroxide production by TPA was detected by a DCHF-DA assay, and the addition of superoxide dismutase (SOD) or tempol significantly inhibited TPA-induced migration/invasion and COX-2 protein expression accompanied by a decrease in peroxide production. An increase in NADPH oxidase activity by TPA was examined, and TPA-induced migration/invasion was blocked by adding DPI, an NADPH oxidase inhibitor. Additionally, the natural flavonoids quercetin (QE), baicalein (BE), and myricetin (ME) effectively blocked TPA-induced migration/invasion while simultaneously inhibiting COX-2/PGE2 production, MMP-9 enzyme activity, and peroxide production in U87 cells. The contribution of ROS production to the migration/invasion of U87 glioblastoma cells via ERK-activated COX-2/PGE2 and MMP-9 induction was first investigated here, and agents such as QE, BE, and ME with the ability to block these events possess the potential to be developed for use against migration/invasion by glioblastomas. 相似文献
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Teh LK Mohamed NI Salleh MZ Rohaizak M Shahrun NS Saladina JJ Shia JK Roslan H Sood S Rajoo TS Muniandy SP Henry G Ngow HA Hla U KT Din J 《The AAPS journal》2012,14(1):52-59
CYP2D6 plays a major role in the metabolism of tamoxifen, and polymorphism of P-glycoprotein has been associated with resistance of many drug therapies. This study investigates the clinical impact of genetic variants of CYP2D6 and ABCB1 in breast cancer patients treated with tamoxifen. Blood samples from 95 breast cancer patients treated with tamoxifen were collected and genotyped for CYP2D6 and ABCB1 variants using allele-specific PCR method. Recurrence risks were calculated using Kaplan-Meier analysis and compared using the log-rank test. Patients carrying CYP2D6*10/*10 and heterozygous null allele (IM) showed higher risks of developing recurrence and metastasis (OR 13.14; 95% CI 1.57-109.94; P = 0.004) than patients with CYP2D6*1/*1 and *1/*10 genotypes. Patients with homozygous CC genotypes of ABCB1 C3435T showed a shorter time to recurrence. Patients who were CYP2D6 IM and homozygous CC genotype of C3435T have statistically significant higher risks of recurrence (P = 0.002). Similarly, median time to recurrence in these patients was only 12 months (95% CI = 0.79-23.2) compared to those without this combination which was 48 months (95% CI = 14.7-81.2). Patients with CYP2D6 IM and homozygous CC genotype of ABCB1 C3435T have shorter times to recurrence. The results confirmed the findings of previous studies and support FDA recommendation to perform pre-genotyping in patients before the choice of therapy is determined in breast cancer patients. 相似文献
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The presence of neuroendocrine cells in adenocarcinomas is not an unusual finding and is well described in gastrointestinal tract cancers, eg, colorectal cancer and gastric cancer. Genetic analysis of such tumors has suggested a common multipotent progenitor stem cell origin. The prognostic significance of neuroendocrine cells in adenocarcinoma cells is unclear. There is a scant literature on synchronous pancreas ductal adenocarcinoma and pancreas neuroendocrine tumors. We report 2 cases with a purpose of discussing management strategies, prognosis, and potential etiologies of this rare presentation. 相似文献
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Schaefer G Haber L Crocker LM Shia S Shao L Dowbenko D Totpal K Wong A Lee CV Stawicki S Clark R Fields C Lewis Phillips GD Prell RA Danilenko DM Franke Y Stephan JP Hwang J Wu Y Bostrom J Sliwkowski MX Fuh G Eigenbrot C 《Cancer cell》2011,20(4):472-486
Extensive crosstalk among ErbB/HER receptors suggests that blocking signaling from more than one family member may be essential to effectively treat cancer and limit drug resistance. We generated a conventional IgG molecule MEHD7945A with dual HER3/EGFR specificity by phage display engineering and used structural and mutational studies to understand how a single antigen recognition surface binds two epitopes with high affinity. As a human IgG1, MEHD7945A exhibited dual action by inhibiting EGFR- and HER3-mediated signaling in?vitro and in?vivo and the ability to engage immune effector functions. Compared with monospecific anti-HER antibodies, MEHD7945A was more broadly efficacious in multiple tumor models, showing that combined inhibition of EGFR and HER3 with a single antibody is beneficial. 相似文献
38.
目的评估剖宫产术患者风险及相光因素,实施预见性护理,降低手术风险,确保母婴安全。方法对352例剖宫产术患者列为对照组,524例剖宫产术患者列为观察组,进行风险评估,实施预见性护理,观察两组新生儿窒息发生和抢救成功率,产后出血、切口感染的发生情况。结果对照组新生儿窒息Ⅰ度窒息有14例,Ⅱ度窒息7例,产后出血7例,切口感染12例,观察组新生儿窒息Ⅰ度窒息有6例,Ⅱ度窒息2例,产后出血2例,切口感染5例。两组比较有差异性,P〈0.05。结论通过对剖宫产术患者进行风险评估.针对性地实施预见性护理,可有效降低新生儿窒息发生率,减少产后出血、切口感染发生率。 相似文献
39.
Shia J Klimstra DS 《The American journal of surgical pathology》2008,32(10):1586-8; author reply 1588-9
40.
Cho CS Curran S Schwartz LH Kooby DA Klimstra DS Shia J Munoz A Fong Y Jarnagin WR DeMatteo RP Blumgart LH D'Angelica MI 《Journal of the American College of Surgeons》2008,206(3):480-488
BACKGROUND: The adverse impact of hepatic steatosis on perioperative outcomes after liver resection is gaining recognition. But the accuracy of preoperative radiologic assessment of fatty liver disease remains unclear. The objective of this study was to correlate preoperative radiologic estimation with postoperative histologic measurement of steatosis. STUDY DESIGN: Patients who underwent partial hepatectomy between 1997 and 2001, with complete preoperative radiographic imaging and postoperative pathologic assessment of steatosis, were retrospectively analyzed. The presence of steatosis was assessed radiographically using noncontrast-enhanced CT (NCCT), contrast-enhanced CT (CCT), or MRI, using standard quantitative radiologic criteria. Repeat histologic analysis was used to quantify the extent of hepatic steatosis. RESULTS: One hundred thirty-one patients were studied. The overall sensitivity and specificity for all imaging modalities in detecting pathologically confirmed hepatic steatosis were 56% and 82%, respectively. Sensitivity and specificity for NCCT, CCT, and MRI using standard quantitative criteria were 33% and 100%, 50% and 83%, and 88%, and 63%, respectively. Increasing body mass indices adversely affected the accuracy of NCCT (p=0.002). Preoperative chemotherapy did not notably affect radiologic accuracy. CONCLUSIONS: The presence of a fatty-appearing liver on NCCT scans indicates clinically significant steatosis, but steatosis cannot be excluded based on a normal NCCT scan, particularly in obese patients. Conversely, normal MRI helps to exclude hepatic steatosis, but abnormal MRI is not a reliable indicator of fatty change. CCT is not an effective means of identifying steatosis. We conclude that, when used alone, conventional cross-sectional imaging does not consistently permit accurate identification of hepatic steatosis. 相似文献