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- Volume 10, Issue 8, 2010
Current Molecular Medicine - Volume 10, Issue 8, 2010
Volume 10, Issue 8, 2010
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MicroRNAs: Macro Challenges on Understanding Human Biological Functions and Neurological Diseases
Authors: C. B. Santos-Reboucas and M. M.G. PimentelMicroRNAS (miRNAs) are a class of endogenously single-stranded non-coding RNA molecules that can negatively modulate the expression of target messenger RNAs by 3´ UTR base pairing. During the processing of a miRNA, a network of orchestrated molecular events provides a dynamic manner to posttranscriptionally modulate gene expression. Recent research has demonstrated that although these molecules are small, they are involved in several crucial biological functions, as well as, in a broad spectrum of human diseases. In this review, we highlighted the current knowledge on the miRNA pathway field, focusing on how the disruption of the miRNA-mediated silencing pathways could lead to the pathogenesis of neurological disorders. The potential use of miRNAs as diagnostic/prognostic markers and the possibility of reversing the effects of some miRNA polymorphisms/mutations by promising therapeutics procedures have brought new perspectives into the treatment of human pathologies.
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Use of Transgenic Mice as Models for Prostate Cancer Chemoprevention
Authors: P. A. Nguewa and A. CalvoProstate cancer is a long latency type of tumor that usually develops in men older than 50 years of age. Prostate epithelial neoplasia (PIN), the initial malignant lesion, progresses to invasive carcinoma over the course of years. Because of the particular features of prostate carcinogenesis, this type of tumor may represent a paradigm for cancer prevention. Several clinical trials have evaluated the effect of different compounds on prostate tumor development, including finasteride, selenium, vitamin E, and carotenes. Although some results are promising, no conclusive data have been achieved as to recommend any of these compounds as preventive agents. Results from some trials, such as SELECT, where supplementation of selenium and/or vitamin-E was used, have been rather disappointing. However, many novel chemopreventive agents that target different cancer-related pathways are being developed lately. Appropriate animal models (in particular, genetically modified mice) are being used to assess the efficacy of these novel compounds. The transgenic adenocarcinoma of the mouse prostate (TRAMP) model has been validated as an accurate model to test a variety of preventive agents. Genistein, alpha-difluoromethylornithine, toremifene, R-flurbiprofen, celecoxib, and green tea polyphenols have been shown to prevent prostate cancer development in TRAMP mice. In conclusion, new chemopreventive compounds which are effective in animal models are likely to be tested soon in clinical trials, with the final goal of reducing prostate cancer incidence in men.
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Optimizing Tumor-Reactive γδT Cells for Antibody-Based Cancer Immunotherapy
Authors: S. Meraviglia, N. Caccamo, G. Guggino, M. Tolomeo, S. Siragusa, G. Stassi and F. DieliMonoclonal antibodies (mAbs) constitute the most rapidly growing class of human therapeutics and the second largest class of drugs after vaccines. The treatment of B-cell malignancies and HER2/Neu+ breast cancer has benefited considerably from the use of therapeutic mAbs, either alone or in combination with standard chemotherapy. Frequent relapses, however, demonstrate that the bioactivity of these mAbs is still suboptimal. The concept of improving the anti-tumor activity of mAbs is well established and potentiating the cytotoxicity induced by anticancer mAbs can be achieved by strategies that target the downstream cytolytic effector cells. The recruitment of Fcγ receptor-dependent functions appears well suited in this regard, because several lines of evidence suggest that enhancing antibody-dependent cellular cytotoxicity (ADCC) induced by therapeutic mAbs may directly improve their clinical efficacy. The cytolytic effector cells involved in ADCC are Fcγ-Rexpressing natural killer (NK) cells, but also γδ T cells can be amplified and finetuned for stronger ADCC activity. γδ T cells are raising a considerable interest in the immunotherapy community given their intrinsic antitumor activity that can be boosted by stimulation with synthetic phosphoantigens (PAgs), or with drugs that cause their accumulation into target cells, like aminobisphosphonates (N-BPs), and low doses interleukin (IL)-2. The field is interesting, and several papers have already explored this approach in solid and haematological malignancies. Thus, we propose that enhancing the efficacy of mAbs by combination with γδ T cell activation may have considerable therapeutic potential for a variety of malignancies, most especially for patients whose FcγR alleles impair ADCC.
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Monocyte and Macrophage Dysfunction as a Cause of HIV-1 Induced Dysfunction of Innate Immunity
Authors: P. Collini, M. Noursadeghi, I. Sabroe, R. F. Miller and D. H. DockrellHIV-1 can establish both long lived and productive infection of macrophages (Mφ) but circulating monocytes are less permissive to infection. Multiple studies have identified extensive changes to monocyte and Mφ phenotype, differentiation or function. These include alterations in Toll-like receptor signaling and resultant changes to cytokine responses, specific defects in phagocytosis and microbial killing and modulation of apoptotic responses, all of which may perturb the important role of these cells in innate immunity. Interpretation of contradictory data however, is complicated by the use of different experimental models and many of the reported effects may be an indirect consequence of HIV-1 infection that result from exposure to viral products or from disruption of cellular and cytokine networks in the immune system, rather than the direct consequence of productive HIV-1 infection. Future research should focus on refining experimental models and on elucidating the physiological mechanisms of monocyte/ Mφ dysfunction during HIV-1 infection.
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Defining the Molecular Nexus of Cancer, Type 2 Diabetes and Cardiovascular Disease
Authors: S. M. Cabarcas, E. M. Hurt and W. L. FarrarThe metabolic syndrome is characterized by a state of metabolic dysfunction resulting in the development of several chronic diseases that are potentially deadly. These metabolic deregulations are complex and intertwined and it has been observed that many of the mechanisms and pathways responsible for diseases characterizing the metabolic syndrome such as type 2 diabetes and cardiovascular disease are linked with cancer development as well. Identification of molecular pathways common to these diverse diseases may prove to be a critical factor in disease prevention and development of potential targets for therapeutic treatments. This review focuses on several molecular pathways, including AMPK, PPARs and FASN that interconnect cancer development, type 2 diabetes and cardiovascular disease. AMPK, PPARs and FASN are crucial regulators involved in the maintenance of key metabolic processes necessary for proper homeostasis. It is critical to recognize and identify common pathways deregulated in interrelated diseases as it may provide further information and a much more global picture in regards to disease development and prevention. Thus, this review focuses on three key metabolic regulators, AMPK, PPARs and FASN, that may potentially serve as therapeutic targets.
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Potentialities of Induced Pluripotent Stem (iPS) Cells for Treatment of Diseases
Authors: C. Chakraborty, K. D. Shah, W. G. Caob, C. H. Hsu, Z. H. Wen and C. S. LinInduced pluripotent stem (iPS) cell research has been growing a new height throughout the world due to its potentialities in medical applications. We can explore several therapeutic applications through the iPS cell research. In this review, we have first discussed the development of iPS cells, reprogramming factors, and effectiveness of iPS cells. Then we have emphasized the potential applications of iPS cells in pharmaceutical and medical sectors, such as, study of cellular mechanisms for spectrum of disease entities, disease-specific iPS cell lines for drugs discovery and development, toxicological studies of drugs development, personalized medicine, and regenerative medicine.
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The Role of Calcium in Intracellular Trafficking
By M. MicaroniThe molecular mechanism of membrane fusion essential to vital cellular activities such as intracellular transport, hormone secretion, enzyme release, or neurotransmission, involve the assembly and disassembly of a specialized set of proteins in opposing bilayers. Recent evidences shed new light on the role Ca2+ has in the regulation of this mechanism in which the Golgi apparatus works as a central station; from here, Ca2+ ions are released into and recovered from the cytosol during the different steps of the cargo progression. In fact, transient cytosolic Ca2+ fluctuations take a crucial role to recruit proteins and enzymes Ca2+-sensitive on Golgi membranes where they are involved in membranes remodelling which is fundamental process for the fusion events that allow protein trafficking. Here I provide an overview of the role Ca2+ plays in intra-Golgi trafficking underlying some interesting aspects to clarify the mechanisms of cargo progression.
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Volumes & issues
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Volume 24 (2024)
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Volume 23 (2023)
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Volume 22 (2022)
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Volume 21 (2021)
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Volume 20 (2020)
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Volume 19 (2019)
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Volume 18 (2018)
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Volume 17 (2017)
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Volume 16 (2016)
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Volume 15 (2015)
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Volume 14 (2014)
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Volume 13 (2013)
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Volume 12 (2012)
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Volume 11 (2011)
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Volume 10 (2010)
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Volume 9 (2009)
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Volume 8 (2008)
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Volume 7 (2007)
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Volume 6 (2006)
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Volume 5 (2005)
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Volume 4 (2004)
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Volume 3 (2003)
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Volume 2 (2002)
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Volume 1 (2001)