TSGF与组合癌谱联合检测在恶性肿瘤中的诊断价值

目的:探讨肿瘤相关物质(TSGF)与组合癌谱(AFP、CEA、Ft、TSA)联合检测在肿瘤诊断中应用价值.方法:用化学法检测TSGF,用ELISA法和化学法检测组合癌谱,并对170例恶性肿瘤、60例非肿瘤患者血清联合检测结果进行分析.结果:TSGF单项检测对肿瘤的诊断阳性率分别为肝癌82%,肺癌87%,胃癌90%,结(直)肠癌86%,而联合检测阳性率为97.5%、97.7%、98.3%、97.5%.结论:TSGF与组合癌谱联合检测提高了肿瘤诊断的阳性率,且又给肿瘤的定位提供了可靠依据,达到早期诊断的目的.     

姜黄素和TSA对胃癌c-myc表达影响

目的了解姜黄素和TSA对胃癌c—myc基因表达影响,探讨组蛋白乙酰化／去乙酰化的动态平衡在胃癌基因表达和调控中的意义。方法进行胃癌细胞株SGC-7901和MGC803培养,然后加入不同浓度的组蛋白乙酰化酶抑制剂姜黄素和组蛋白去乙酰化酶抑制剂TSA分别进行干预,RT—PCR检测c—myc的mRNA的表达。结果通过RT—PCR的检测我们发现随着姜黄素的浓度增加及TSA浓度的减小c—myc的表达受到抑制（P〈0．01）。结论姜黄素与TSA对c—myc表达影响作用是相反的。     

Utilization of recombinant Fab fragments in a cTnI immunoassay conducted in spot wells

OBJECTIVES: To evaluate the performance of a new cTnI immunoassay utilizing site-specifically biotinylated recombinant Fab fragments on recently established spot wells. DESIGN AND METHODS: Two different cTnI-specific recombinant site-specifically biotinylated Fab fragments were produced. The performance of the new sandwich-type cTnI immunoassay in spot wells was evaluated in terms of binding capacity, assay kinetics and assay sensitivity and compared with a cTnI immunoassay carried out in conventional microtitration wells. Furthermore, the functionality of the recombinant Fab fragments was compared to the corresponding monoclonal antibodies in assay with one, two or three capture antibodies. RESULTS: The signal-to-background level was improved, providing an analytical detection limit of 0.002 microg/l with a surface of two capture Fab fragments. The spot wells increased the signal levels 2-fold and a further 4-fold improvement was detected with the Fab fragments already after 5 min assay time. CONCLUSIONS: The spot-concept in combination with site-oriented capture Fab fragments carries great promise as a very useful approach to improve the immunoassay performance of future point-of-care cTnI assays.     

Histone deacetylase inhibition enhances adenoviral vector transduction in inner ear tissue

Adenovirus vectors (AdVs) are efficient tools for gene therapy in many tissues. Several studies have demonstrated successful transgene transduction with AdVs in the inner ear of rodents [Kawamoto K, Ishimoto SI, Minoda R, Brough DE, Raphael Y (2003) J Neurosci 23:4395–4400]. However, toxicity of AdVs [Morral N, O'Neal WK, Rice K, Leland MM, Piedra PA, Aguilar-Cordova E, Carey KD, Beaudet AL, Langston C (2002) Hum Gene Ther 13:143–154.] or lack of tropism to important cell types such as hair cells [Shou J, Zheng JL, Gao WQ (2003) Mol Cell Neurosci 23:169–179] appears to limit their experimental and potential clinical utility. Histone deacetylase inhibitors (HDIs) are known to enhance AdV-mediated transgene expression in various organs [Dion LD, Goldsmith KT, Tang DC, Engler JA, Yoshida M, Garver RI Jr (1997) Virology 231:201–209], but their effects in the inner ear have not been documented. We investigated the ability of one HDI, trichostatin A (TSA), to enhance AdV-mediated transgene expression in inner ear tissue. We cultured neonatal rat macular and cochlear explants, and transduced them with an AdV encoding green fluorescent protein (Ad-GFP) under the control of a constitutive promoter for 24 h. In the absence of TSA, GFP expression was limited, and very few hair cells were transduced. TSA did not enhance transduction when applied at the onset of Ad-GFP transduction. However, administration of TSA during or just after Ad-GFP application increased GFP expression in supporting cells approximately fourfold. Moreover, vestibular hair cell transduction was enhanced approximately sixfold, and that of inner hair cells by more than 17-fold. These results suggest that TSA increases AdV-mediated transgene expression in the inner ear, including the successful transduction of hair cells. HDIs, some of which are currently under clinical trials (Sandor et al., 2002), could be useful tools in overcoming current limitations of gene therapy in the inner ear using Ad-GFP.     

Bone geometry in cercopithecoid mandibles

This study explores the relation between cortical bone geometry in the mandibular corpus and in vivo masticatory stress patterns and dietary specialization in cercopithecoid primates. Cortical bone distribution in the mandibles of three species of Old World monkeys (Macaca fascicularis, Procolobus badius, Lophocebus albigena) was measured by computed tomography. The arrangement of bone within sections was quantified as (1) the ratio of cortical area to the enclosed (total) subperiosteal area; (2) the ratio of orthogonal second moments of area; and (3) size-adjusted measures of cortical area and regional thickness. Cross-sectional geometry differed among samples, but consistent patterns of cortical thinning and bone area were found within individual sections. This consistency was despite the marked differences in diet and feeding behavior that distinguish the three taxa. Lingually thin and basally thick cortical bone was found in the three monkeys; previously published data suggest that this pattern may be stereotypical among anthropoid primates. It is hypothesized that the interactive effects of shear, bending and torsion produce eccentric loads in corpus sections, which are mirrored by this asymmetrical arrangement of cortical bone. When interpreted against existing data for other primate groups, these results are consistent with the hypothesis that masticatory-loading profiles are broadly similar across anthropoids despite the distinctive occlusions found among the suborder. Understanding of the impact of diet on jaw morphology is, therefore, not improved by considerations of cortical bone distribution, i.e. the inference of diet from jaw form is best predicated on considerations of relative corpus size rather than cross-sectional geometry.     

Antitumor efficacy of FK228, a novel histone deacetylase inhibitor,depends on the effect on expression of angiogenesis factors

It has been recently demonstrated that histone deacetylase inhibitors inhibit angiogenesis, but their mechanism of action has not been characterized well. In this study, we examined the in vitro and in vivo effects of FK228 [(E)-(1S,4S,10S,21R)-7-[(Z)-ethylidene]-4,21-diisopropyl-2-oxa-12,13-dithia-5,8,20,23-tetraazabicyclo-[8,7,6]-tricos-16-ene-3,6,9,19,22-pentanone; FR901228, depsipeptide], an HDAC inhibitor, on the expression of angiogenesis factors in FK228-sensitive PC-3 prostate and FK228-resistant ACHN renal cancer cells. FK228 suppressed the expression of VEGF mRNA in PC-3 cells, but not in ACHN cells. FK228 also suppressed the expression of basic fibroblast growth factor (bFGF) mRNA in both PC-3 and ACHN cells. Under conditions of hypoxia, FK228 suppressed the expression of VEGF mRNA without modulating the expression of hypoxia-inducible factor-1 alpha mRNA in PC-3 cells. FK228 induced the highest acetylation of histone H3 and H4 in the P2 region of the VEGF promoter, which includes the hypoxia-inducible factor-1 alpha binding site that plays an important role in regulating the expression of VEGF gene. Moreover, FK228 reduced the amount of VEGF and bFGF protein, and their mRNA levels in PC-3 xenograft implanted in nude mice, but did not reduce them in ACHN xenograft. In conclusion: (i) FK228 showed a suppressive effect on the expression of angiogenesis factors, such as VEGF and bFGF, in PC-3 xenograft but not in ACHN xenograft, which suggests that the effect on the expression of angiogenesis factors is important for the antitumor efficacy of FK228; (ii) FK228 caused histone acetylation of the VEGF promoter regions, which may contribute to the suppression of VEGF gene expression.