P16基因及其表达在非小细胞肺癌中的研究进展

目的：使我们对P^16基因及其表达在非小细胞肺癌(non-small cell lung cancer NSCLC)的早期诊断及治疗从分子水平上有进一步的认识。方法：就P^16基因在NSCLC人中的近期研究进展作一综述。结果：P^16（也称多肿瘤的抑制基因，MTS1和CDKN2)，它是一种抑癌基因。原发性NSCLC组织均可出现P^16／P^15基因纯合性丢失。肺鳞癌组织P^16基因的甲基化明显高于其它组织类型。在NSC比中病期愈晚P^16蛋白缺失越明显。被检病人痰及血中的P^16基因异常，有助于NSCLC的早期诊断。P^16和P^53基因联合共转染能显增强对NSCLC细胞增殖的抑制。结论：P^16基因及其表达蛋白与NSCLC的发生、发展、转移密切相关，应用于NSCLC的早期诊断及治疗。     

自反Banach空间上C0半群的一些结果

设T（t）是自反Banach空间X上满足两个条件的一类C0半群。本文证明如果T（t）是弱L^p稳定的，则其生成元的谱界是负的。再由文献[1]得到的关于这一类C0半群在任何Banach空间上其增长界都与生成元谱界相等的结果得出，自反Banach空间上此类半群弱L^p稳定与指数稳定等价。     

苯乙酸对甲苯酯的改进合成

苯乙酸和对甲酚在二环已基碳二酰亚胺(DCC)存在下，用4—二甲氨基吡啶(DMAP)作催化剂合成苯乙酸对甲苯酯，反应时间短，反应条件温和，后处理容易，产率高。     

确定碎石桩复合地基桩土应力比的一种新方法

探讨软基处理碎石桩径向变形机理 ,提出碎石桩体变形模式的纵横向异性 ,并根据桩土变形协调引入魏西克圆孔扩张理论和 p- y曲线法得出桩土应力比计算式 .     

关于收敛p级数的一般估值不等式

本文建立收敛p级数的一般估值不等式.     

单级单步多导数方法的代数稳定性

本文从文献［１］中有关多值多导数方法的弱代数稳定性概念引伸出单级单步多导数方法的代数稳定性概念，并建立了若干单级单步多导数方法为代数稳定的充分条件与充要条件。     

Reversible histone acetylation／deacetylation modification by p300 and HDAC3 is involved in the regulation of IL-18 promoter activity

Interleukin-18 (IL-18) is a pleiotropic cytokine involved in the development of T helper type 1 (Thl) cells, and it plays important roles in regulation of both the innate and acquired immune responses. The aim of this study was to elucidate whether the reversible histone acetylation/ deacetylation modification participates in the regulation of IL-18 transcription expression. The transcription coactivator p300 containing the histone acetyltransferase (HAT) activity, and the histone deacetylase 3 (HDAC3) were used in this study to analyze the effect of this modification in the regulation of mouse IL-18 gene. The results demonstrate that transfection of p300-expression plasmid promotes the endogenous IL-18 mRNA synthesis in J774 cells, and stimulates the activation of IL-18 promoter. It has been found that this stimulating effect of p300 was reversed by HDAC3, indicating the involvement of the reversible histone acetylation/deacetylation modification in IL-18 regulation. Furthermore, the data show that the HAT activity of p300 was essential to its function in activating IL-18 promoter. In addition, p300 was shown to be able to work synergistically with the transcription factor c-Fos on activation of IL-18 promoter and this effect could also be impaired by HDAC3. Results presented in this paper indicate that the reversible histone acetylation/deacetylation modification plays an important role in the transcriptional regulation of IL-18.     

Isolation of human epidermal stem cells by adherence and the reconstruction of skin equivalents

The isolation of human epidermal stem cells is critical for their clinical applications. In the present study, we isolated three populations of epidermal keratinocytes according to their ability to adhere to collagen type IV: i.e., rapidly adhering (RA), slowly adhering (SA), and non-adhering (NA) cells. The aim of this study was to characterize RA cells and to investigate the possibility of using these cells for epidermis reconstruction. To identify RA cells, flow cytometric analysis was performed using anti-p5/xxlarge945.gif" alt="agr" align="BASELINE" BORDER="0">₆ integrin and anti-CD71 antibodies. RA cells express high levels of p5/xxlarge945.gif" alt="agr" align="BASELINE" BORDER="0">₆ integrin and low levels of CD71, which are considered as markers of an epidermal stem cell nature. Furthermore, electron microscopy showed that RA cells are small and have a high nuclear to cytoplasmic ratio, whereas SA and NA cells have well-developed cellular organelles and abundant tonofilaments. Western blot analysis showed that RA cells are slow cycling and express p63, a putative epidermal stem cell marker, whereas SA and NA cells express c-Myc, which is known to regulate stem cell fate. To compare epidermal regenerative abilities, skin equivalents (SEs) were made using RA, SA, and NA cells. The epidermis constructed from RA cells was well formed compared to those formed from SA or NA cells. In addition, only SEs with RA cells expressed p5/xxlarge945.gif" alt="agr" align="BASELINE" BORDER="0">₆ integrin and p5/xxlarge946.gif" alt="beta" align="MIDDLE" BORDER="0">₁ integrin at the basal layer. These results indicate that RA cells represent epidermal stem cells and are predominately comprised of stem cells. Therefore, the isolation of RA cells using a simple technique offers a potential route to their clinical application, because they are easily isolated and provide a high yield of epidermal stem cells.Received 2 July 2004; received after revision 20 August 2004; accepted 10 September 2004     

Oligomer-mediated modulation of hTERT alternative splicing induces telomerase inhibition and cell growth decline in human prostate cancer cells

The expression of telomerase in human cells is strictly controlled by multiple mechanisms including transcription and alternative splicing of telomerase reverse transcriptase (hTERT). In this study, we demonstrated the possibility of modulating the hTERT splicing pattern in DU145 human prostate carcinoma cells through the use of 2'-O-methyl-RNA phosphorothioate oligonucleotides targeting the splicing site located between intron 5 and exon 6 in the hTERT pre-mRNA. An 18-h oligonucleotide exposure induced a decrease in the full-length hTERT transcript and a concomitant increase in the alternatively spliced transcripts, which resulted in significant inhibition of telomerase catalytic activity. Moreover, exposure to the R7 oligomer (which induced the most pronounced modulation of the hTERT splicing pattern and the greatest telomerase inhibition) caused a marked reduction in DU145 cell growth and the induction of apoptosis starting 2 days after treatment. Such data support the concept that down-regulation of hTERT expression can cause short-term effects on tumour cell growth, which are telomere-shortening independent.     

Apoptotic cell death in the lactating mammary gland is enhanced by a folding variant of α-lactalbumin

Apoptosis is essential to eliminate secretory epithelial cells during the involution of the mammary gland. The environmental regulation of this process is however, poorly understood. This study tested the effect of HAMLET (human p3fa8p2xw2e/xxlarge945.gif" alt="agr" align="BASELINE" BORDER="0">-lactalbumin made lethal to tumor cells) on mammary cells. Plastic pellets containing HAMLET were implanted into the fourth inguinal mammary gland of lactating mice for 3 days. Exposure of mammary tissue to HAMLET resulted in morphological changes typical for apoptosis and in a stimulation of caspase-3 activity in alveolar epithelial cells near the HAMLET pellets but not more distant to the pellet or in contralateral glands. The effect was specific for HAMLET and no effects were observed when mammary glands were exposed to native a-lactalbumin or fatty acid alone. HAMLET also induced cell death in vitro in a mouse mammary epithelial cell line. The results suggest that HAMLET can mediate apoptotic cell death in mammary gland tissue.Received 30 January 2004; received after revision 5 March 2004; accepted 16 March 2004