光动力疗法对兔肝癌肿瘤微血管密度及血管内皮细胞生长因子的影响

目的：研究光动力疗法对兔肝＇VX2移植癌模型的抑瘤作用及其可能的机制,为临床应用 PDT 治疗肝癌提供依据;方法用15只新西兰白兔制成VX2细胞肝癌模型。以血卟啉衍生物（HPD）为光敏剂观察PDT的抑瘤效果,应用免疫组化染色检测VEGF及MVD的表达水平;结果 PDT对肿瘤明显的杀伤作用;PDT组中VEGF及Mr＇VD的表达水平显著的低于对照组（p〈0.05）;结论 PDT可抑制兔肝VX2移植癌中肿瘤灶VEGF的生成,减少肿瘤灶内MVD。PDT抗肿瘤血管形成是其抑制肿瘤生长的一个重要机制。     

Oxidation and tyrosine phosphorylation: synergistic or antagonistic cues in protein tyrosine phosphatases

Protein tyrosine phosphatases (PTPs) have been generally recognised as key modulators of cell proliferation, differentiation, adhesion and motility. During signalling, several PTPs undergo two posttranslational modifications that greatly affect their enzymatic activity: tyrosine phosphorylation and cysteine oxidation. Although these modifications share their reversibility depending on the intracellular environment, their effects on enzymatic activity are opposite, tyrosine phosphorylation being correlated to enzyme activation and thiol oxidation to complete inactivation. Several papers have suggested that both these modifications occur in response to the same stimuli i.e. cell proliferation induced by numerous growth factors and cytokines. Conversely, the possibility that these two regulation mechanisms act simultaneously on PTPs has not been established and very few reports investigated this dual regulation of PTPs. To underline the relevance of the question, we discuss several possibilities: (i) that tyrosine phosphorylation and cysteine oxidation of PTPs may share the same target molecules but with different kinetics; (ii) that PTP phosphorylation and oxidation may take place on different subcellular pools of the same protein and (iii) that these two modifications, although having divergent effects on enzyme activity, cooperate in the integrated and coordinated function of PTPs during receptor tyrosine kinase signalling. We believe that our perspective will open new perspectives on an ancient problem – the apparent contradiction of opposing enzymatic regulation of many PTPs – thus clarifying their role as positive or negative transducers (or both) of many extracellular stimuli.Received 11 October 2004; received after revision 26 January 2005; accepted 10 February 2005 Available online 29 March 2005     

Recognition of bacterial peptidoglycan by the innate immune system

The innate immune system recognizes microorganisms through a series of pattern recognition receptors that are highly conserved in evolution. Peptidoglycan (PGN) is a unique and essential component of the cell wall of virtually all bacteria and is not present in eukaryotes, and thus is an excellent target for the innate immune system. Indeed, higher eukaryotes, including mammals, have several PGN recognition molecules, including CD14, Toll-like receptor 2, a family of peptidoglycan recognition proteins, Nod1 and Nod2, and PGN-lytic enzymes (lysozyme and amidases). These molecules induce host responses to microorganisms or have direct antimicrobial effects.Received 15 January 2003; received after revision 28 February 2003; accepted 26 March 2003     

EGF receptor induction and insulin-EGF overlap inTetrahymena

Summary Offspring generations ofTetrahymena pretreated (imprinted) with insulin showed a greater binding capacity for the hormone than offspring of untreated ones. The epidermal growth factor (EGF) imprinted for insulin to a greater degree than insulin itself, and vice versa: insulin imprinted for EGF more efficiently than EGF itself. These phenomena can be explained by the overlap of insulin and EGF on one another's receptors inTetrahymena.     

Melatonin and circadian control in mammals

Summary Although pinealectomy has little influence on the circadian locomotor rhythms of laboratory rats, administration of the pineal hormone melatonin has profound effects. Evidence for this comes from studies in which pharmacological doses of melatonin are administered under conditions of external desynchronization, internal desynchronization, steady state light-dark conditions, and phase shifts of the zeitgeber. Taken together with recent findings on melatonin receptor concentration in the rat hypothalamus, particularly at the level of the suprachiasmatic nuclei, these results suggest that melatonin is a potent synchronizer of rat circadian rhythms and has a direct action on the circadian pacemaker. It is possible, therefore, that the natural role of endogenous melatonin is to act as an internal zeitgeber for the total circadian structure of mammals at the level of cell, tissue, organ, whole organism and interaction of that organism with environmental photoperiod changes.