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Multiple Molecular Pathways (multiple + molecular_pathway)
Selected AbstractsCell survival and apoptosis-related molecules in cancer cells in effusions: A comprehensive reviewDIAGNOSTIC CYTOPATHOLOGY, Issue 8 2009Lilach Kleinberg Ph.D. Abstract Spreading of cancer cells to effusions is a manifestation of advanced disease, for which the chances of achieving cure using conventional treatment are low. This emphasizes both the importance of improving early detection and the need for developing targeted therapy modes. Such approaches should be based on characterization of the antiapoptotic, survival and drug resistance mechanisms of the metastatic cells in addition to analysis of the primary tumor. This review presents current knowledge regarding the expression and clinical role of cell survival and apoptosis-related molecules in nonhematological cancers in effusions. Differences in the anatomic site-related expression and clinical role of these proteins are additionally discussed. The data presented highlight the complexity of the multiple molecular pathways that mediate tumor cell survival within the serosal cavities. Diagn. Cytopathol. 2009. © 2009 Wiley-Liss, Inc. [source] Epidemiology and carcinogenesis of hepatocellular carcinomaHPB, Issue 1 2005TRISHE Y.-M. Abstract The incidence of hepatocellular carcinoma (HCC) shows marked variation worldwide but the magnitude of this tumor is reflected by the occurrence of at least 1 million new cases annually and the uniformly dismal outlook with median survivals of <25 months after resection and <6 months with symptomatic treatment. The strikingly uneven distribution of this tumor parallels the prevalence of hepatitis B infection with rising incidence in western countries attributed to hepatitis C infection. Chronic hepatitis and cirrhosis constitute the major preneoplastic conditions in the majority of HCCs and may be related to other etiologic agents such as environmental chemical carcinogens including nitrites, hydrocarbons, solvents, organochlorine pesticides, and the chemicals in processed foods, cleaning agents, cosmetics and pharmaceuticals, as well as plant toxins such as aflatoxins produced by fungi that cause spoilage of grain and food in the tropics. Genetic diseases such as genetic hematochromatosis, Wilson's disease, ,-1-antitrypsin deficiency, and the inborn errors of metabolism including hereditary tyrosinemia and hepatic porphyria, are known to be associated with HCC. Numerous genetic alterations and the modulation of DNA methylation are recognized in HCC and it is likely that these genetic and epigenetic changes combine with factors involved in chronic hepatocyte destruction and regeneration to result in neoplastic growth and multiple molecular pathways may be involved in the production of subsets of hepatocellular tumors. [source] Functional and molecular MR imaging of angiogenesis: Seeing the target, seeing it workJOURNAL OF CELLULAR BIOCHEMISTRY, Issue S39 2002Michal NeemanArticle first published online: 16 JAN 200 Abstract Intensive research over the last years led to the discovery of multiple molecular pathways and intricate regulatory network controlling the growth and regression of blood vessels in general and angiogenesis in particular. The difficulties in elucidation of the regulation of angiogenesis, stems from the inherent complexity due to participation of many cell types, under a dominant impact of physiological and environmental effects of flow, perfusion, and oxygenation. Major advances were achieved with the use of sophisticated transgenic mice models engineered so as to provide spatially and temporally controlled expression of specific factors alone or in combination. In vivo analysis of these models frequently requires the use of non-invasive imaging modalities for measurement of functional parameters of the vasculature along with dynamic molecular information. Optical methods are extensively applied for the study of angiogenesis [Brown et al., 2001] but provide very limited tissue penetration. MRI offers the advantage of being non-invasive with uniform and relatively high spatial resolution for deep tissues. Multiple MRI approaches for monitoring angiogenesis were developed over the last years, each looking at a particular step in the process. The aim of this paper is to analyze the clinical, pharmaceutical, and biological needs for imaging of angiogenesis, and to critically evaluate the strengths and weaknesses of functional and molecular imaging for monitoring angiogenesis. The inherent problem of validation of different measures of angiogenesis, and the advantages and limitations associated with application of MRI based methods, as surrogates for other measurements of angiogenesis will be discussed. The terms molecular imaging and functional imaging are frequently loosely defined with a significant overlap between the two. For the sake of this paper we will apply a narrower definition of both terms, where molecular imaging will apply to methods directed towards detection of specific biological molecules that participate directly in (regulation of) a physiological process; while functional imaging will be used to describe those methods that aim to detect the physiological response to a defined (molecular) stimulus. J. Cell. Biochem. Suppl. 39: 11,17, 2002. © 2002 Wiley-Liss, Inc. [source] Redox proteomics identification of 4-hydroxynonenal-modified brain proteins in Alzheimer's disease: Role of lipid peroxidation in Alzheimer's disease pathogenesisPROTEOMICS - CLINICAL APPLICATIONS, Issue 6 2009Marzia Perluigi Abstract Numerous studies have shown that neuronal lipids are highly susceptible to oxidative stress including in those brain areas directly involved in the neurodegenerative process of Alzheimer's disease (AD). Lipid peroxidation directly damages membranes and also generates a number of secondary biologically active products (toxic aldehydes)that are capable of easily attacking lipids, proteins, and DNA. Accumulating evidence has demonstrated regionally increased brain lipid peroxidation in patients with AD; however, extensive studies on specific targets of lipid peroxidation-induced damage are still missing. The present study represents a further step in understanding the relationship between oxidative modification of protein and neuronal death associated with AD. We used a proteomics approach to determine specific targets of lipid peroxidation in AD brain, both in hippocampus and inferior parietal lobule, by coupling immunochemical detection of 4-hydroxynonenal-bound proteins with 2-D polyacrylamide gel electrophoresis and MS analysis. We identified 4-hydroxynonenal-bound proteins in the hippocampus and inferior parietal lobule brain regions of subjects with AD. The identified proteins play different biological functions including energy metabolism, antioxidant system, and structural proteins, thus impairing multiple molecular pathways. Our results provide further evidence for the role of lipid peroxidation in the pathogenesis of AD. [source] Germ cell apoptosis induced by experimental cryptorchidism is mediated by molecular pathways in mouse testisANDROLOGIA, Issue 1 2010F. Absalan Summary The aim of the study was to characterise the alterations in expression of some apoptosis regulators in unilaterally and bilaterally heat-treated mouse testes at different time intervals to 42 days after surgery. Cryptorchidism was induced in immature mice by returning the testis to the abdominal cavity via a surgical procedure. Transcript levels of Bax, Bcl-2 proper, p53 and survivin mRNA and protein were determined in normal and cryptorchid testes using reverse transcription polymerase chain reaction (RT-PCR) and immunohistochemistry. RT-PCR data verified the elevation of p53 expression and decrease of Bax and Bcl-2 proper mRNA in the cryptorchid testis in a time-dependent manner. The expression of survivin 140 and 40 variants strongly decreased in the bilateral groups compared with unilateral and control groups. These changes were significantly different in the bilateral groups in comparison with the unilateral groups. Immunohistochemistry data showed that the intensity of p53 and Bax expression mainly increased in the remainder cells in the cryptorchid testis and the rates of Bcl-2 proper and survivin expression decreased mainly in the bilateral groups. These observations suggest that multiple molecular pathways participate in the germ cell apoptosis induced by cryptorchidism. [source] | |||||||||||||