EXS最新文献

{"title":"Genetic and environmental factors in hereditary predisposition to tumors: a conceptual overview.","authors":"Okio Hino,&nbsp;Toshiyuki Kobayashi,&nbsp;Kazuo Okimoto","doi":"10.1007/3-7643-7378-4_11","DOIUrl":"https://doi.org/10.1007/3-7643-7378-4_11","url":null,"abstract":"<p><p>Cancer is a heritable disorder of somatic cells. Carcinogenesis at the cellular level is like an opened Japanese fan, because initiated cells grow in several directions and tumors suggest the edge of the fan by having many gene abnormalities. We discuss here the primal force and gene networks (federal headship) in renal carcinogenesis. The Eker (Tsc2 mutant) rat model of hereditary renal carcinoma (RC) is an example of a Mendelian dominantly inherited predisposition to a specific cancer in an experimental animal. Recently, we discovered a new hereditary renal carcinoma in the rat in Japan, and the rat was named the \"Nihon\" rat. We suggest that its predisposing (Bhd) gene is a novel renal tumor suppressor gene. We present these unique models as part of the study of problems in carcinogenesis; e.g., multistep carcinogenesis, cancer prevention and the development of the therapeutic treatments that can be translated to human patients, as well as how environmental factors interact with cancer susceptibility gene(s).</p>","PeriodicalId":77125,"journal":{"name":"EXS","volume":" 96","pages":"269-92"},"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_11","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25775067","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":"Modulator role of neuropeptide Y in human vascular sympathetic neuroeffector junctions.","authors":"M Verónica Donoso,&nbsp;Ana María Delpiano,&nbsp;J Pablo Huidobro-Toro","doi":"10.1007/3-7643-7417-9_4","DOIUrl":"https://doi.org/10.1007/3-7643-7417-9_4","url":null,"abstract":"<p><p>Reverse transcription polymerase chain reaction (RT-PCR) studies identified the mRNA coding for the Y1 and Y2 receptors in human mammary artery/vein and saphenous vein biopsies. Y1 receptors are expressed in vascular smooth muscles and potentiate the contractile action of sympathetic co-transmitters, adenosine triphosphate (ATP) and noradrenaline (NA); BIBP 3226, a competitive Y1 receptor antagonist, blocked the neuropeptide Y (NPY)-induced modulation. The Y2 receptor is expressed in sympathetic nerves terminals and modulates the pool of sympathetic co-transmitters released at the neuroeffector junction. NPY plays a dual role as a modulator of sympathetic co-transmission; it facilitates vascular smooth muscle reactivity and modulates the presynaptic release of ATP and NA. Sympathetic reflexes regulate human vascular resistance, where NPY plays a modulator role of paramount importance following increased sympathetic discharges, such as stress and vascular disease.</p>","PeriodicalId":77125,"journal":{"name":"EXS","volume":" 95","pages":"65-76"},"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_4","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25775173","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 neuron-adipocyte interactions in the regulation of metabolism.","authors":"L Christine Turtzo,&nbsp;M Daniel Lane","doi":"10.1007/3-7643-7417-9_10","DOIUrl":"https://doi.org/10.1007/3-7643-7417-9_10","url":null,"abstract":"","PeriodicalId":77125,"journal":{"name":"EXS","volume":" 95","pages":"133-41"},"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_10","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25775179","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":"The rationale for studying transmitter interactions to understand the neural bases of cognitive function.","authors":"Edward D Levin","doi":"10.1007/978-3-7643-7772-4_1","DOIUrl":"https://doi.org/10.1007/978-3-7643-7772-4_1","url":null,"abstract":"","PeriodicalId":77125,"journal":{"name":"EXS","volume":"98 ","pages":"1-3"},"PeriodicalIF":0.0,"publicationDate":"2006-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"26291394","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":"Forebrain dopaminergic-cholinergic interactions, attentional effort, psychostimulant addiction and schizophrenia.","authors":"Martin Sarter,&nbsp;John P Bruno,&nbsp;Vinay Parikh,&nbsp;Vicente Martinez,&nbsp;Rouba Kozak,&nbsp;Jerry B Richards","doi":"10.1007/978-3-7643-7772-4_4","DOIUrl":"https://doi.org/10.1007/978-3-7643-7772-4_4","url":null,"abstract":"","PeriodicalId":77125,"journal":{"name":"EXS","volume":"98 ","pages":"65-86"},"PeriodicalIF":0.0,"publicationDate":"2006-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/978-3-7643-7772-4_4","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"26291397","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":"Modulation of visual perception and action by forebrain structures and their interactions in amphibians.","authors":"Jiörg-Peter Ewert,&nbsp;Wolfgang W Schwippert","doi":"10.1007/978-3-7643-7772-4_6","DOIUrl":"https://doi.org/10.1007/978-3-7643-7772-4_6","url":null,"abstract":"","PeriodicalId":77125,"journal":{"name":"EXS","volume":"98 ","pages":"99-136"},"PeriodicalIF":0.0,"publicationDate":"2006-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/978-3-7643-7772-4_6","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"26291399","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 regulation of tumor angiogenesis: mechanisms and therapeutic implications.","authors":"Jay Harper,&nbsp;Marsha A Moses","doi":"10.1007/3-7643-7378-4_10","DOIUrl":"https://doi.org/10.1007/3-7643-7378-4_10","url":null,"abstract":"<p><p>Angiogenesis, the process of new capillary formation from a pre-existing vessel plays an essential role in both embryonic and postnatal development, in the remodeling of various organ systems, and in several pathologies, particularly cancer. In the last 20 years of angiogenesis research, a variety of angiogenic regulators, both positive and negative, have been identified. The discovery of several anti-angiogenic factors has led to the development of novel cancer therapies based on targeting a tumor's vascular supply. A number of these new therapies are currently being tested in clinical trials in the U.S.A. and elsewhere. A major advance in the field of anti-angiogenic therapy occurred recently when the FDA approved Avastin (bevacizumab), the first solely anti-angiogenesis therapy approved for treatment of human cancer. While it has long been appreciated that tumor growth and progression are dependent on angiogenesis, it is only recently that progress has been made in elucidating the molecular mechanisms that regulate the earliest stage in the angiogenic program, the angiogenic switch. This checkpoint is characterized by the transition of a dormant, avascular tumor into an active, vascular one. Anti-angiogenic therapies to date have essentially been designed to suppress the neovasculature in established tumors. However, identifying the mechanisms that cause a tumor to acquire an angiogenic phenotype may lead to the discovery of new therapeutic modalities and complementary diagnostics that could be used to block the angiogenic switch, thereby preventing subsequent tumor progression. In this chapter on the role of angiogenesis in cancer, we (1) provide an overview of the process of angiogenesis with special regard to the molecules and physiological conditions that regulate this process, (2) review recent studies describing the use of anti-angiogenic approaches in the treatment of a variety of human cancers, and (3) discuss the recent literature focused on the study of the molecules and molecular mechanisms that may be regulating the initiation of the angiogenic phenotype in tumors, and the clinical impact that this knowledge may have in the future.</p>","PeriodicalId":77125,"journal":{"name":"EXS","volume":" 96","pages":"223-68"},"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_10","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25775066","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":"The mode of action of organic carcinogens on cellular structures.","authors":"Andreas Luch","doi":"10.1007/3-7643-7378-4_4","DOIUrl":"https://doi.org/10.1007/3-7643-7378-4_4","url":null,"abstract":"<p><p>Most genotoxic organic carcinogens require metabolic activation to exert their detrimental effects. The present review summarizes the mechanisms of how organic carcinogens are bioactivated into DNA-reactive descendants. Beginning with the history of discovery of some important human organic carcinogens, the text guides through the development of the knowledge on their molecular mode of action that has grown over the past decades. Some of the most important molecular mechanisms in chemical carcinogenesis, the role of the enzymes involved in bioactivation, the target gene structures of some ultimate carcinogenic metabolites, and implications for human cancer risk assessment are discussed.</p>","PeriodicalId":77125,"journal":{"name":"EXS","volume":" 96","pages":"65-95"},"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_4","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25775150","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 ultraviolet light on cellular structures.","authors":"David I Pattison,&nbsp;Michael J Davies","doi":"10.1007/3-7643-7378-4_6","DOIUrl":"https://doi.org/10.1007/3-7643-7378-4_6","url":null,"abstract":"<p><p>Solar radiation is the primary source of human exposure to ultraviolet (UV) radiation. Overexposure without suitable protection (i.e., sunscreen and clothing) has been implicated in mutagenesis and the onset of skin cancer. These effects are believed to be initiated by UV-mediated cellular damage, with proteins and DNA as primary targets due to a combination of their UV absorption characteristics and their abundance in cells. UV radiation can mediate damage via two different mechanisms: (a) direct absorption of the incident light by the cellular components, resulting in excited state formation and subsequent chemical reaction, and (b) photosensitization mechanisms, where the light is absorbed by endogenous (or exogenous) sensitizers that are excited to their triplet states. The excited photosensitizers can induce cellular damage by two mechanisms: (a) electron transfer and hydrogen abstraction processes to yield free radicals (Type I); or (b) energy transfer with O2 to yield the reactive excited state, singlet oxygen (Type II). Direct UV absorption by DNA leads to dimers of nucleic acid bases including cyclobutane pyrimidine species and pyrimidine (6-4) pyrimidone compounds, together with their Dewar isomers. These three classes of dimers are implicated in the mutagenicity of UV radiation, which is typified by a high level of CC-->TT and C-->T transversions. Single base modifications can also occur via sensitized reactions including Type 1 and Type II processes. The main DNA product generated by (1)O2 is 8-oxo-Gua; this is a common lesion in DNA and is formed by a range of other oxidants in addition to UV. The majority of UV-induced protein damage appears to be mediated by (1)O2, which reacts preferentially with Trp, His, Tyr, Met, Cys and cystine side chains. Direct photo-oxidation reactions (particularly with short-wavelength UV) and radicals can also be formed via triplet excited states of some of these side chains. The initial products of (1)O2-mediated reactions are endoperoxides with the aromatic residues, and zwitterions with the sulfur-containing residues. These intermediates undergo a variety of further reactions, which can result in radical formation and ring-opening reactions; these result in significant yields of protein cross-links and aggregates, but little protein fragmentation. This review discusses the formation of these UV-induced modifications and their downstream consequences with particular reference to mutagenesis and alterations in protein structure and function.</p>","PeriodicalId":77125,"journal":{"name":"EXS","volume":" 96","pages":"131-57"},"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_6","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25775152","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":"Abnormalities of cell structures in tumors: apoptosis in tumors.","authors":"Herman H Cheung,&nbsp;Vinay Arora,&nbsp;Robert G Korneluk","doi":"10.1007/3-7643-7378-4_9","DOIUrl":"https://doi.org/10.1007/3-7643-7378-4_9","url":null,"abstract":"<p><p>A conceptual shift has occurred in recent years from considering cancer as simply a disease of deregulated cell proliferation to a view that incorporates the aberrant control of apoptosis into the equation. Apoptosis is an organized, genetically programmed cell death process by which multicellular organisms specifically destroy, dismantle and dispose of cells. In cancer cells, this tightly controlled process is suppressed by genetic lesions, allowing cancer cells to survive beyond their normal life span even in hostile environments that are prone to hypoxia and lack many trophic factor supports. In the last two decades, cancer researchers have made great strides in our understanding of the underlying molecular mechanism of apoptosis in chemoresistance generation and tumorigenesis. This tremendous increase in our knowledge of apoptosis in tumors has greatly impacted our perspective on carcinogenesis. Key regulators of apoptosis such as members of the Inhibitors of Apoptosis family and Bcl-2 family have been shown to play a pivotal role in allowing most cancer cells to escape apoptosis. The identification of specific targets involved in the suppression of apoptosis in cancer cells has facilitated the design and development of therapeutic strategies based on rational molecular approaches that aim to modulate apoptotic pathways. Many promising apoptosis-dependent strategies have been translated into clinical trials in the continued assessment of regimens that can effectively eradicate cancers.</p>","PeriodicalId":77125,"journal":{"name":"EXS","volume":" 96","pages":"201-21"},"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_9","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25775155","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}