EXS最新文献

{"title":"NPY and extreme stress: lessons learned from posttraumatic stress disorder.","authors":"Mary Ann Dutton, Edward W Lee, Zofia Zukowska","doi":"10.1007/3-7643-7417-9_16","DOIUrl":"https://doi.org/10.1007/3-7643-7417-9_16","url":null,"abstract":"","PeriodicalId":77125,"journal":{"name":"EXS","volume":" 95","pages":"213-22"},"PeriodicalIF":0.0,"publicationDate":"2006-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/3-7643-7417-9_16","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25775184","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular mechanisms of human carcinogenesis.","authors":"William B Coleman,&nbsp;Gregory J Tsongalis","doi":"10.1007/3-7643-7378-4_14","DOIUrl":"https://doi.org/10.1007/3-7643-7378-4_14","url":null,"abstract":"<p><p>Intensive research efforts during the last several decades have increased our understanding of carcinogenesis, and have identified a genetic basis for the multi-step process of cancer development. Tumors grow through a process of clonal expansion driven by mutation. Several forms of molecular alteration have been described in human cancers, and these can be generally classified as chromosomal abnormalities and nucleotide sequence abnormalities. Most cancer cells display a phenotype characterized by genomic hypermutability, suggesting that genomic instability may precede the acquisition of transforming mutations in critical target genes. Reduced to its essence, cancer is a disease of abnormal gene expression, and these genetic abnormalities contribute to cancer pathogenesis through inactivation of negative mediators of cell proliferation (including tumor suppressor genes) and activation of positive mediators of cell proliferation (including proto-oncogenes). In several human tumor systems, specific genetic alterations have been shown to correlate with well-defined histopathological stages of tumor development and progression. Although the significance of mutations to the etiological mechanisms of tumor development has been debated, a causal role for such genetic lesions is now commonly accepted for most human cancers. Thus, genetic lesions represent an integral part of the processes of neoplastic transformation, tumorigenesis, and tumor progression, and as such represent potentially valuable markers for cancer detection and staging.</p>","PeriodicalId":77125,"journal":{"name":"EXS","volume":" 96","pages":"321-49"},"PeriodicalIF":0.0,"publicationDate":"2006-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/3-7643-7378-4_14","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25775070","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Aneuploidy, stem cells and cancer.","authors":"Sen Pathak,&nbsp;Asha S Multani","doi":"10.1007/3-7643-7378-4_3","DOIUrl":"https://doi.org/10.1007/3-7643-7378-4_3","url":null,"abstract":"<p><p>Telomeres which protect the individual chromosomes from disintegration, end-to-end fusion and maintain the genomic integrity during the somatic cell divisions play an important role in cellular aging. Aging and cancer development are linked with each other because cancer is considered a group of complex genetic diseases that develop in old cells and, in both, telomere attrition is involved. Numeric chromosome imbalance also known as aneuploidy is the hallmark of most solid tumors, whether spontaneous or induced by carcinogens. We provide evidence in support of the hypothesis that telomere attrition is the earliest genetic alteration responsible for the induction of aneuploidy. Dysfunctional telomeres are highly recombinogenic leading to the formation of dicentric chromosomes. During cell divisions, such complex chromosome alterations undergo breakage fusion bridge cycles and may lead to loss of heterozygosity (LOH) and gene amplification. Furthermore, we have provided evidence in support of the hypothesis that all types of cancer originate in the organ- or tissue-specific stem cells present in a particular organ. Cancer cells and stem cells share many characteristics, such as, self-renewal, migration, and differentiation. Metaphases with abnormal genetic constitution present in the lymphocytes of cancer patients and in some of their asymptomatic family members may have been derived from the organ-specific stem cells. In addition, evidence and discussion has been presented for the existence of cancer-specific stem cells. Successful treatment of cancer, therefore, should be directed towards these cancer stem cells.</p>","PeriodicalId":77125,"journal":{"name":"EXS","volume":" 96","pages":"49-64"},"PeriodicalIF":0.0,"publicationDate":"2006-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/3-7643-7378-4_3","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25775149","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Actions of radiation on living cells in the \"post-bystander\" era.","authors":"Carmel Mothersill,&nbsp;C B Seymour","doi":"10.1007/3-7643-7378-4_7","DOIUrl":"https://doi.org/10.1007/3-7643-7378-4_7","url":null,"abstract":"<p><p>Over the past 20 years there has been increasing evidence that cells and the progeny of cells surviving a dose of ionizing radiation can exhibit a wide range of effects inconsistent with the level of dose received. Recently, the cause of these delayed effects has been ascribed to so-called bystander effects, occurring in cells not directly hit by an ionizing track, but which are influenced by signals from irradiated cells. These effects are not necessarily deleterious, although most of the literature deals with adverse delayed effects. What is important to consider is what, if anything, these effects mean for what is still the central dogma of radiobiology and radiation protection, i.e., that DNA double-strand breaks are the primary radiation-induced lesion that can be quantifiably related to received dose, and which determine the probability that a cancer will result from a radiation exposure. In this chapter we review the history of radiation biology which led to the DNA paradigm. We explore the issues and the evidence which are now challenging the view that dose deposition in DNA is all important. We conclude that in the low-dose region, the primary determinant of radiation exposure outcome is the genetic and epigenetic background of the individual and not the dose. This effectively dissociates dose from effect as a quantitative relationship, but it does not necessarily mean that the effect is unrelated to DNA damage somewhere in the system.</p>","PeriodicalId":77125,"journal":{"name":"EXS","volume":" 96","pages":"159-77"},"PeriodicalIF":0.0,"publicationDate":"2006-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/3-7643-7378-4_7","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25775153","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cancer morphology, carcinogenesis and genetic instability: a background.","authors":"Leon P Bignold,&nbsp;B L D Coghlan,&nbsp;H P A Jersmann","doi":"10.1007/3-7643-7378-4_1","DOIUrl":"https://doi.org/10.1007/3-7643-7378-4_1","url":null,"abstract":"<p><p>Morphological abnormalities of both the nuclei and the cell bodies of tumour cells were described by Müller in the late 1830s. Abnormalities of mitoses and chromosomes in tumour cells were described in the late 1880s. Von Hansemann, in the 1890s, suggested that tumour cells develop from normal cells because of a tendency to mal-distribution and other changes of chromosomes occurring during mitosis. In the first decades of the 20th century, Mendelian genetics and \"gene mapping\" of chromosomes were established, and the dominant or recessive bases of the familial predispositions to certain tumour types were recognised. In the same period, the carcinogenic effects of ionising radiations, of certain chemicals and of particular viruses were described. A well-developed \"somatic gene-mutational theory\" of tumours was postulated by Bauer in 1928. In support of this, in the next three decades, many environmental agents were found to cause mitotic and chromosomal abnormalities in normal cells as well as mutations in germ-line cells of experimental animals. Nevertheless, mitotic, chromosomal, and other mutational theories were not popular explanations of tumour pathogenesis in the first half of the 20th century. Only in the 1960s did somatic mutational mechanisms come to dominate theories of tumour formation, especially as a result of the discoveries of the reactivity of carcinogens with DNA, and that the mutation responsible for xeroderma pigmentosum causes loss of function of a gene involved in the repair of DNA after damage by ultraviolet light (Cleaver in 1968). To explain the complexity of tumourous phenomena, \"multi-hit\" models gained popularity over \"single-hit\" models of somatic mutation, and \"epigenetic\" mechanisms of gene regulation began to be studied in tumour cells. More recently, the documentation of much larger-than-expected numbers of genomic events in tumour cells (by Stoler and co-workers, in 1999) has raised the issue of somatic genetic instability in tumour cells, a field which was pioneered in the 1970s mainly by Loeb. Here these discoveries are traced, beginning with \"nuclear instability\" though mitotic-and-chromosomal theories, single somatic mutation theories, \"multi-hit\" somatic theories, \"somatic, non-chromosomal, genetic instability\" and epigenetic mechanisms in tumour cells as a background to the chapters which follow.</p>","PeriodicalId":77125,"journal":{"name":"EXS","volume":" 96","pages":"1-24"},"PeriodicalIF":0.0,"publicationDate":"2006-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/3-7643-7378-4_1","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25775188","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An overview of neuropeptide Y: pharmacology to molecular biology and receptor localization.","authors":"Yvan Dumont,&nbsp;Rémi Quirion","doi":"10.1007/3-7643-7417-9_2","DOIUrl":"https://doi.org/10.1007/3-7643-7417-9_2","url":null,"abstract":"","PeriodicalId":77125,"journal":{"name":"EXS","volume":" 95","pages":"7-33"},"PeriodicalIF":0.0,"publicationDate":"2006-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/3-7643-7417-9_2","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25774702","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetic instability in human tumors.","authors":"Stavroula Raptis,&nbsp;Bharati Bapat","doi":"10.1007/3-7643-7378-4_13","DOIUrl":"https://doi.org/10.1007/3-7643-7378-4_13","url":null,"abstract":"<p><p>Genetic, or genomic, instability refers to a series of observed spontaneous genetic changes occurring at an accelerated rate in cell populations derived from the same ancestral precursor. This is far from a new finding, but is one that has increasingly gained more attention in the last decade due to its plausible role(s) in tumorigenesis. The majority of genetic alterations contributing to the malignant transformation are seen in growth regulatory genes, and in genes involved in cell cycle progression and arrest. Genomic instability may present itself through alterations in the length of short repeat stretches of coding and non-coding DNA, resulting in microsatellite instability. Tumors with such profiles are referred to as exhibiting a mutator phenotype, which is largely a consequence of inactivating mutations in DNA damage repair genes. Genomic instability may also, and most commonly, results from gross chromosomal changes, such as translocations or amplifications, which lead to chromosomal instability. Telomere length and telomerase activity, important in maintaining chromosomal structure and in regulating a normal cell's lifespan, have been shown to have a function in both suppressing and facilitating malignant transformation. In addition to such direct sequence and structural changes, gene silencing through the hypermethylation of promoter regions, or increased gene expression through the hypomethylation of such regions, together, form an alternative, epigenetic mechanism leading to instability. Emerging evidence also suggests that dietary and environmental agents can further modulate the contribution of genetic instability to tumorigenesis. Currently, there is still much debate over the distinct classes of genomic instability and their specific roles in the initiation of tumor formation, as well as in the progressive transition to a cancerous state. This review examines the various molecular mechanisms that result in this genomic instability and the potential contribution of the latter to human carcinogenesis.</p>","PeriodicalId":77125,"journal":{"name":"EXS","volume":" 96","pages":"303-20"},"PeriodicalIF":0.0,"publicationDate":"2006-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/3-7643-7378-4_13","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25775069","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Viral carcinogenesis and genomic instability.","authors":"Karl Münger,&nbsp;Hiroyuki Hayakawa,&nbsp;Christine L Nguyen,&nbsp;Nadja V Melquiot,&nbsp;Anette Duensing,&nbsp;Stefan Duensing","doi":"10.1007/3-7643-7378-4_8","DOIUrl":"https://doi.org/10.1007/3-7643-7378-4_8","url":null,"abstract":"<p><p>Oncogenes encoded by human tumor viruses play integral roles in the viral conquest of the host cell by subverting crucial and relatively non-redundant regulatory circuits that regulate cellular proliferation, differentiation, apoptosis and life span. Human tumor virus oncoproteins can also disrupt pathways that are necessary for the maintenance of the integrity of host cellular genome. Some viral oncoproteins act as powerful mutator genes and their expression dramatically increases the incidence of host cell mutations with every round of cell division. Others subvert cellular safeguard mechanisms intended to eliminate cells that have acquired abnormalities that interfere with normal cell division. Viruses that encode such activities can contribute to initiation as well as progression of human cancers.</p>","PeriodicalId":77125,"journal":{"name":"EXS","volume":" 96","pages":"179-99"},"PeriodicalIF":0.0,"publicationDate":"2006-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/3-7643-7378-4_8","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25775154","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"NPY and NPY receptors: presence, distribution and roles in the regulation of the endocardial endothelium and cardiac function.","authors":"Danielle Jacques,&nbsp;Sawsan Sader,&nbsp;Claudine Perreault,&nbsp;Dima Abdel-Samad","doi":"10.1007/3-7643-7417-9_5","DOIUrl":"https://doi.org/10.1007/3-7643-7417-9_5","url":null,"abstract":"","PeriodicalId":77125,"journal":{"name":"EXS","volume":" 95","pages":"77-87"},"PeriodicalIF":0.0,"publicationDate":"2006-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/3-7643-7417-9_5","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25775174","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neuropeptide Y and the cerebral circulation.","authors":"Lars Edvinsson","doi":"10.1007/3-7643-7417-9_7","DOIUrl":"https://doi.org/10.1007/3-7643-7417-9_7","url":null,"abstract":"","PeriodicalId":77125,"journal":{"name":"EXS","volume":" 95","pages":"105-12"},"PeriodicalIF":0.0,"publicationDate":"2006-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/3-7643-7417-9_7","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25775176","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}