SHP2及其在乳腺癌发生发展中的作用

SHP2是一种非受体型蛋白酪氨酸磷酸酶,其介导的信号转导异常与多种疾病包括肿瘤的发生和发展密切相关,对SHP2的深入研究有助于对其作用机制的阐明以及潜在药物学靶点的发现。本文简要介绍了SHP2的结构、功能及其介导的Ras/ERK信号通路,并着重阐述了SHP2与乳腺癌发展的关系。     

The role of PML in tumor suppression

The PML gene, involved in the t(15;17) chromosomal translocation of acute promyelocytic leukemia (APL), encodes a protein which localizes to the PML-nuclear body, a subnuclear macromolecular structure. PML controls apoptosis, cell proliferation, and senescence. Here, we review the current understanding of its role in tumor suppression.     

The role of PML ubiquitination in human malignancies

Tumor suppressors are frequently downregulated in human cancers and understanding of the mechanisms through which tumor cells restrict the expression of tumor suppressors is important for the prognosis and intervention of diseases. The promyelocytic leukemia (PML) protein plays a critical role in multiple tumor suppressive functions, such as growth inhibition, apoptosis, replicative senescence, suppression of oncogenic transformation, and inhibition of migration and angiogenesis. These tumor suppression functions are recapitulated in several mouse models. The expression of PML protein is frequently downregulated in diverse types of human tumors and this downregulation often correlates with tumor progression. Recent evidence has emerged that PML is aberrantly degraded in various types of tumors through ubiquitination-dependent mechanisms. Here, we summarize our current understanding of the PML ubiquitination/degradation pathways in human cancers. We point out that multiple pathways lead to PML ubiquitination and degradation. Furthermore, the PML ubiquitination processes are often dependent on other types of posttranslational modifications, such as phosphorylation, prolylisomerization, and sumoylation. Such feature indicates a highly regulated nature of PML ubiquitination in different cellular conditions and cell contexts, thus providing many avenues of opportunity to intervene PML ubiquitination pathways. We discuss the potential of targeting PML ubiquitination pathways for anti-cancer therapeutic strategies.     

The role of acid catalysis in the genesis of amber

Analysis of the hydrocarbon fraction from baltic amber is described. Transformations which have occurred in resins during the formation of amber are discussed on the grounds of acid-catalysed reactions undergone by 7,13-abietadiene and sclareol.     

The ubiquitous and varied role of infection in the lives of animals and plants

Parasitic and symbiotic infections are major forces governing the life histories of plant and animal hosts-a fact that is ever more evident because of recent findings emanating from diverse subdisciplines of biology. Yet, infectious organisms have been relatively little investigated by biologists who study natural populations. Now that new molecular and computational tools allow us to differentiate and track microscopic infectious agents in nature, we are beginning to establish a better appreciation of their effects on larger, more familiar organisms. This special issue on the ecological and evolutionary consequences of infection for plants and animals is based on the annual Vice Presidential Symposium at the meeting of the American Society of Naturalists held in Knoxville, Tennessee, in the summer of 2001.     

New insights into the role of PML in tumour suppression

The PML gene is involved in the t(15;17) translocation of acute promyelocytic leukaemia (APL), which generates the oncogenic fusion protein PML (promyelocytic leukaemia protein)-retinoic acid receptor alpha. The PML protein localises to a subnuclear structure called the PML nuclear domain (PML-ND), of which PML is the essential structural component. In APL, PML-NDs are disrupted, thus implicating these structures in the pathogenesis of this leukaemia. Unexpectedly, recent studies indicate that PML and the PML-ND play a tumour suppressive role in several different types of human neoplasms in addition to APL. Because of PML's extreme versatility and involvement in multiple cellular pathways, understanding the mechanisms underlying its function, and therefore role in tumour suppression, has been a challenging task. In this review, we attempt to critically appraise the more recent advances in this field and propose new avenues of investigation.     

The role of dyslipoproteinemia in the genesis of chronic hepatitis]

The dynamics of structural changes in the liver in experimental dyslipoproteinemia (DLP) and its correction was studied. Vessel-tissue changes found in the liver of rabbits in a short-term and stable DLP (4, 8 weeks) can be estimated as different stages of chronic active hepatitis. The microcirculation disorders and structural changes in the liver appeared at the early stages of DLP in the absence of atheromatosis in large arteries. The pathological changes in the liver existed 36 weeks after the rejection of atherogenic diet and correlated with DLP. Thus, DLP can be the risk factor as cardiovascular diseases as chronic nonspecific changes in the target organs.     

Lymphangiogenesis and its role in cancer

In many tumour types, lymphatic vasculature serves as a major route for tumour metastasis. The dissemination of malignant cells to the regional lymph nodes is an early step in the progression of many solid tumours and is an important determinant of prognosis. Lymphangiogenesis (formation of new lymphatic vessels) is thought to be crucial for cancer cells to metastasise to the regional lymph nodes. However research in this important process has been neglected largely due to the lack of molecular markers specific to the lymphatic endothelium. Recently, several specific markers have been identified including LYVE-1, podoplanin and prox-1. Although the biology of lymphangiogeneis, particularly its regulation, is still far from clear, it is now well established that tumours are lymphangiogenic i.e. they could induce the generation of their own lymphatics and metastasise to the regional lymph nodes. It is thought that the interruption of the main signalling pathways involved in this process could help to prevent lymphatic spread of many tumours. Furthermore, understanding the molecular mechanisms in lymphangiogenesis might help to develop new therapeutic strategies against cancer lymphatic spread. Here, we reviewed the literature in regards to the biology of lymphangiogenesis, its molecular regulation, lymphatic markers and the significance in human solid tumours.     

The human fungal pathogen Malassezia and its role in cancer

Malassezia belongs to the fungal division Basidiomycota and plays an important role in the mycobiome of the mammalian system. The fungus propagates by budding and mostly remains commensal with the host comprising of warm-blooded animals. During infection, it converts from yeast to its pathogenic hyphal form and this leads to many diseases in humans. Currently, there are 18 known species of Malassezia out of which 11 species are related to humans and the prevalence of the species varies with geographical location. In addition to several diseases it causes, recent research shows the direct role of the fungus in promoting oncogenesis. The fungus thrives with a fine balance between commensalism and its pathogenic state. Its high lipid content in the cell wall provides a robust defense system against the host immunogenic factors. In this review, we discuss the role of the fungus and its host cell receptors in promoting inflammation and disease. We highlight the potential procancerous role of the metabolites produced by Malassezia in tumor development and highlight how the antimicrobial peptides like Defensin and Nanovesicles like MalaEx modulate the host defense system. Finally, we discuss the importance of fungal dysbiosis caused by Malassezia and its role in human diseases. Though working with the fungus is difficult for several reasons, utilizing modern genomic approaches to understanding the biology of this fungus is of tremendous clinical importance. This review highlights different ways by which the fungus affects human health and often leads to several life-threatening diseases including cancer.     

The biology of Ku and its potential oncogenic role in cancer

Ku is a heterodimeric protein made up of two subunits, Ku70 and Ku80. It was originally identified as an autoantigen recognized by the sera of patients with autoimmune diseases. It is a highly versatile regulatory protein that has been implicated in multiple nuclear processes, e.g., DNA repair, telomere maintenance and apoptosis. Accordingly, Ku is thought to play a crucial role in maintenance of chromosomal integrity and cell survival. Recent reports suggest that there is a positive relationship between Ku and the development of cancer, making Ku an important candidate target for anticancer drug development. Specifically, prior studies suggest that a delicate balance exists in Ku expression, as overexpression of Ku proteins promotes oncogenic phenotypes, including hyperproliferation and resistance to apoptosis; whereas deficient or low expression of Ku leads to genomic instability and tumorigenesis. Such observations through various experimental models indicate that Ku may act as either a tumor suppressor or an oncoprotein. Hence, understanding the link between the various functions of Ku and the development of cancer in different cell systems may help in the development of novel anticancer therapeutic agents that target Ku. These studies may also increase our understanding of how Ku autoantibodies are generated in autoimmune diseases.     

Primary sleep in vertebrates and its role in the genesis of hypobiosis in poikilotherms and hibernation in mammals

New data are presented on the homology between winter hibernation and hypobiosis in poikilotherms, as well as one of the resting forms of the primary sleep in vertebrates. Different stages of formation of a cycle "awakefulness-sleep" in evolution of vertebrates are discussed. On the basis of universal behavioural, somato-vegetative, neurophysiological, neurochemical correlates of resting forms, hypobiosis and winter hibernation, a discussion is made of the problem of genetic fixation in the genotype and phenotype of heterothermic mammals (hibernating ones) of those characters which are typical of the sleep in homoiothermic and poikilothermic vertebrates.     

The role of different microorganisms in the genesis of tubal-peritoneal infertility and in immunity

The character of microflora, directly causing inflammatory process in tuboperitoneal infertility, was studied. The study revealed the prevalence of microbial associations, Chlamydia infection was detected in half of the women, and in 17% of the patients this infection was for the first time detected in the upper section of their reproductive apparatus, which was indicative of the role of Chlamydia infection in the occlusion of the uterine tubes. Opportunistic microflora persisting in persons with defective antimicrobial protection was found. The study of local protective factors in peritoneal fluid revealed the absence of T-cell activity, which was manifested by a low level of sIL-2R and the absence of a significant rise in the level of IL-2 in peritoneal fluid in comparison with that in healthy women. In addition, a decrease in the total complement activity and in the activity of component C3 of the complement was established.