Inactivation of the apoptosis effector Apaf-1 in malignant melanoma

Metastatic melanoma is a deadly cancer that fails to respond to conventional chemotherapy and is poorly understood at the molecular level. p53 mutations often occur in aggressive and chemoresistant cancers but are rarely observed in melanoma. Here we show that metastatic melanomas often lose Apaf-1, a cell-death effector that acts with cytochrome c and caspase-9 to mediate p53-dependent apoptosis. Loss of Apaf-1 expression is accompanied by allelic loss in metastatic melanomas, but can be recovered in melanoma cell lines by treatment with the methylation inhibitor 5-aza-2'-deoxycytidine (5aza2dC). Apaf-1-negative melanomas are invariably chemoresistant and are unable to execute a typical apoptotic programme in response to p53 activation. Restoring physiological levels of Apaf-1 through gene transfer or 5aza2dC treatment markedly enhances chemosensitivity and rescues the apoptotic defects associated with Apaf-1 loss. We conclude that Apaf-1 is inactivated in metastatic melanomas, which leads to defects in the execution of apoptotic cell death. Apaf-1 loss may contribute to the low frequency of p53 mutations observed in this highly chemoresistant tumour type.     

GC/MS法追踪摇头丸杂质体系

本文运用GS/MS的总离子流法,选择离子法,对南京地区常见的几种摇头丸进行全面分析,找出与合成途径相关的痕量杂质,根据杂质情况初步确定其合成途径.     

鲁克沁构造带稠油成藏机制研究

吐哈盆地台南凹陷鲁克沁构造带中的北西走向断层受挤压强烈 ,封闭性好 ;而北东走向断层封闭性差 ,常成为油气运移的良好通道。由于本区断块圈闭的有效性差 ,故不具备大规模聚集稀油的条件 ,但对稠变到一定程度的稠油能起较好的封堵作用。鲁克沁构造带高粘重质油的形成是原油运移和成藏阶段双重稠变作用的结果 ,并且油气的聚集是一个动态的过程。随着原油的逐渐稠变 ,所需要的封堵条件逐渐降低 ,油气的聚集过程才趋于稳定。鲁克沁构造带构造后期变革主要表现在构造幅度的增大 ,而未发生强烈的断裂作用 ,因此 ,前侏罗系油藏得以完好地保存     

BRAFE600-associated senescence-like cell cycle arrest of human naevi

Most normal mammalian cells have a finite lifespan, thought to constitute a protective mechanism against unlimited proliferation. This phenomenon, called senescence, is driven by telomere attrition, which triggers the induction of tumour suppressors including p16(INK4a) (ref. 5). In cultured cells, senescence can be elicited prematurely by oncogenes; however, whether such oncogene-induced senescence represents a physiological process has long been debated. Human naevi (moles) are benign tumours of melanocytes that frequently harbour oncogenic mutations (predominantly V600E, where valine is substituted for glutamic acid) in BRAF, a protein kinase and downstream effector of Ras. Nonetheless, naevi typically remain in a growth-arrested state for decades and only rarely progress into malignancy (melanoma). This raises the question of whether naevi undergo BRAF(V600E)-induced senescence. Here we show that sustained BRAF(V600E) expression in human melanocytes induces cell cycle arrest, which is accompanied by the induction of both p16(INK4a) and senescence-associated acidic beta-galactosidase (SA-beta-Gal) activity, a commonly used senescence marker. Validating these results in vivo, congenital naevi are invariably positive for SA-beta-Gal, demonstrating the presence of this classical senescence-associated marker in a largely growth-arrested, neoplastic human lesion. In growth-arrested melanocytes, both in vitro and in situ, we observed a marked mosaic induction of p16(INK4a), suggesting that factors other than p16(INK4a) contribute to protection against BRAF(V600E)-driven proliferation. Naevi do not appear to suffer from telomere attrition, arguing in favour of an active oncogene-driven senescence process, rather than a loss of replicative potential. Thus, both in vitro and in vivo, BRAF(V600E)-expressing melanocytes display classical hallmarks of senescence, suggesting that oncogene-induced senescence represents a genuine protective physiological process.     

求取剩余油饱和度的一种实用方法

分析了水驱油田地质、测井及开发动态特征，提出了用生产井含水率资料结合测井资料求取产层平均剩余油饱和度的方法。阐述了该方法的基本模型和计算过程，并以实例计算说明了这种方法的实际应用效果。结果表明，该方法操作简便、实用性强、计算结果可靠，且能准确反映储层的剩余油分布特征。这种方法也避免了水淹层混合液电阻率、岩电系数和水淹层电阻率求取值失真的影响。     

渤海湾盆地早第三纪构造样式与油气藏的关系

渤海湾盆地早第三纪构造样式可归结为５种基本类型和３个演化序列。研究结果表明,构造样式及其演化控制着烃源岩的发育,决定着油气藏的类型和展布,制约着含油气系统的范围。综合考虑含油气系统的各个要素,在渤海湾盆地可划分出６个大的含油气系统,分别位于各个坳陷中,并受坳陷的限制。进一步考虑坳陷内凸起构造单元的分割作用,可划分出１３个小的含油气系统。     

临清坳陷莘县凹陷油气勘探远景评价

对莘县凹陷的构造、沉积、盆地模拟及油气勘探远景等进行了深入研究。结果表明,该凹陷具有浅、中、深３个勘探层次,浅层馆陶组和沙一段以储集次生油及低成熟油气为主;中层沙二段、沙三段以自生自储型油藏为主;深层孔二段以储集高成熟油气、石炭－二迭系以煤成气为主。此地区有着极广阔的勘探远景。     

松辽盆地南部低渗透砂岩储层裂缝特征及其对油田开发的影响

松辽盆地南部的低渗透砂岩储层中普遍存在受断层和沉积微相控制的４组高角度构造裂缝,其中以近东西向裂缝渗透性最好,北西向和北东向两组裂缝对储层中流体的渗流也起着相当重要作用,这３组裂缝是油田开发井网布置时应考虑的主要因素。在泥岩夹层中,除了高角度构造裂缝外,还发育有低角度顺层滑脱裂缝,因此,该区泥岩的吸水能力普遍较强,对注水效果有重要影响,因而在注水时应严格控制注入压力。