196,181 research outputs found

    Emerging Role of microRNAs in Prostate Cancer: Implications for Personalized Medicine

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    MicroRNAs (miRNAs) are small non-coding RNAs that negatively regulate gene expression. Recent findings indicate that miRNAs are dysregulated in human tumors, suggesting a potential role for these molecules in the pathogenesis of cancer. Thus far, only a limited number of studies have investigated miRNA expression in prostate cancer. Results from these studies indicate that miRNA expression profiles may distinguish carcinoma from non-neoplastic specimens and further classify tumors according to androgen dependence. In addition, a prognostic significance was attributed to specific miRNAs as predictors of clinical recurrence following radical prostatectomy. For a handful of miRNAs, for which a widespread dysregulation in prostate cancer was consistently found, functional investigation has been pursued in prostate cancer experimental models to establish the rationale for the development of miRNA-based therapies. A better understanding of the role exerted by specific miRNAs in the development and progression of prostate cancer is needed, as is a precise definition of their targets relevant to the disease. However, based on available findings, a possible role for miRNAs in the management of prostate cancer as novel biomarkers and new therapeutic targets or intervention tools can be envisioned

    Towards the definition of prostate cancer-related microRNAs: where are we now?

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    Eradication of advanced prostate cancer still represents an unsolved clinical problem, making the development of alternative treatment approaches highly desirable. Understanding the molecular alterations that distinguish non-progressive from progressive disease would provide mechanistic information for the identification of new therapeutic targets. Recent findings indicate that human tumors have deregulated expression of microRNAs, which have thus been proposed as novel oncogenes or tumor suppressors. A few studies have analyzed the expression profiles or the functional role of microRNAs in prostate cancer, generating largely inconsistent data. Here we review the major issues that have hindered the identification of prostate cancer-related microRNAs, outlining an approach for rational validation of candidates that might be clinically relevant in the management of this disease

    Targeting the telosome: Therapeutic implications

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    AbstractSince telomere integrity is required to guarantee the unlimited replicative potential of cancer cells, telomerase, the enzyme responsible for telomere length maintenance in most human tumors, and lately also telomeres themselves have become extremely attractive targets for new anticancer interventions. At the current status of knowledge, it is still not possible to define the best therapeutic target between telomerase and telomeres. It is noteworthy that interfering with telomeres, through direct targeting of telomeric DNA or proteins involved in the telosome complex, could negatively affect the proliferative potential not only of tumors expressing telomerase activity but also of those that maintain their telomeres through alternative lengthening or still unknown mechanisms. This review presents the different therapeutic approaches proposed thus far and developed in preclinical tumor models and discusses the perspectives for their use in the clinical setting

    MicroRNAs and the Response of Prostate Cancer to Anti-Cancer Drugs

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    Despite considerable advances in early diagnosis, prostate cancer (PCa) remains the second leading cause of cancer-related deaths in men in western countries. In fact, although efficient therapies exist for early-stage disease, the treatment of advanced PCa remains unsuccessful mainly due to its poor responsiveness to anti-cancer agents. This evidence underlines the urgent need for the development of novel and more effective therapeutic approaches. In this context, the documented dysregulation of microRNAs (miRNAs) -which are short non-coding RNAs that regulate gene expression at post-transcriptional level-in PCa, together with their potential to simultaneously regulate multiple oncogenic/tumor-suppressive pathways, has stimulated interest in defining a functional association between altered expression of specific miRNAs and the response of PCa to anti-cancer agents. The purpose of this review is to provide an overview on PCa-related miRNAs as potential novel therapeutic targets/tools, with a special focus on the role that they may play in conditioning the responsiveness of PCa to anti-cancer drugs

    MicroRNAs in Prostate Cancer: A Possible Role as Novel Biomarkers and Therapeutic Targets?

    No full text
    Eradication of advanced prostate cancer still represents an unsolved clinical problem, making the development of alternative treatment approaches highly desirable. Understanding the molecular alterations that distinguish the non-progressive from progressive disease will allow the identification of novel biomarkers for improved staging and prognostication, and will also provide mechanistic information to facilitate treatment selection and design of novel therapeutic approaches. MicroRNAs (miRNAs) are small non-coding RNAs that negatively regulate gene expression. Recent findings indicate that miRNAs are deregulated in human tumors, suggesting a potential role for these molecules in the pathogenesis of cancer. Thus far, only a limited number of studies have investigated miRNA expression in prostate cancer. Results indicate that miRNA expression profiles may distinguish carcinoma from non-neoplastic specimens and further classify tumors according to androgen dependence. In addition, a prognostic significance has been attributed to specific miRNAs as predictors of clinical recurrence following radical prostatectomy. These findings, together with the documented possibility to detect cancer-related miRNAs in blood and core biopsies, open a window on the possibility to utilize them as novel biomarkers. For a handful of miRNAs, functional investigation has also been pursued in prostate cancer experimental models to establish the rationale for the development of miRNA-based therapies. However, a better understanding of the role exerted by specific miRNAs in the onset and progression of prostate cancer is needed, as is a precise definition of their targets relevant to the disease, before translating these molecules into the clinical setting

    RNA Interference-Mediated Validation of Survivin and Apollon/BRUCE as New Therapeutic Targets for Cancer Therapy

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    The ability to evade apoptosis is one of the defining hallmarks of cancer. It enables the survival of cancer cells under abnormal growth stimulation and mediates their increased resistance to treatment with cytotoxic drugs and radiation. Therefore, antiapoptotic proteins that counteract apoptosis signaling represent promising new therapeutic targets to impair cancer cell growth and enhance treatment response. As soon as RNA interference (RNAi) was demonstrated in mammalian cells, it rapidly became an essential tool for gene knockdown in preclinical models, making it possible to define the role of specific genes in the onset and progression of cancer and explore their potential as therapeutic targets. The present review summarizes the findings from studies relying on the use of RNAi-based approaches to functionally validate two members of the inhibitors of apoptosis protein family, survivin and Apollon/BRUCE, as new cancer therapeutic targets. Results collected thus far indicate that targeting the survivin network efficiently inhibits tumor growth potential and increases spontaneous and treatment-induced apoptosis of cancer cells. Based on these findings, the applicability of survivin-directed strategies for the clinical treatment of human tumors is currently under investigation. As regards Apollon/BRUCE, although very preliminary, results of RNAi-mediated gene knockdown point to the possibility to significantly impair tumor cell proliferation through the induction of apoptosis

    Data for Figures 4, A-F and Table J of Publication "Blue skies over China: The effect of pollution-control on solar power generation and revenues"

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    This repository contains the data to produce Figures 4, A-F and Table J and emission data in the paper: "Labordena M, Neubauer D, Folini D, Patt A, Lilliestam J (2018) Blue skies over China: The effect of pollution-control on solar power generation and revenues. PLoS ONE 13(11): e0207028. https://doi.org/10.1371/journal.pone.0207028" Note that the scripts are to be found in the accompanying package (https://doi.org/10.5281/zenodo.8130726

    Quality and Nutraceutical Content of Blueberries (Vaccinium corymbosum) Grown at Two Different Altitudes (450 and 650 m a.s.l.)

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    The production of blueberry in Italy has been growing in recent decades, in response to consumer interest in fruit rich in bioactive compounds with potential dietary anticarcinogens. The study analyzed ripening indices and antioxidant compounds of two blueberry cultivars (‘Brigitta Blue’ and ‘Duke’) grown in Valtellina, Northern Italy during the 2005 and 2006 growing seasons at two different altitudes (450 and 650 m ASL). Fruits were sampled weekly in four classes from mature green to fully ripe berries. Color, total soluble solids, firmness, total phenolics, total anthocyanins, and ascorbic acid were evaluated in blueberries of each ripening class. Greater altitude delayed ripening, color development, and fruit size of ‘Duke’, and enhanced the ascorbic acid content during the ripening process, without influencing other parameters. ‘Brigitta Blue’ attained a higher (about 20%) sugar content and fruit size, while ‘Duke’ showed 50% more total anthocyanins and ascorbic acid, and 25-30% more total phenolics. These traits could be attributed to cultivar and to the earlier ripening of ‘Duke.

    MicroRNAs as new therapeutic targets and tools in cancer

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    Introduction: MicroRNAs (miRNAs) are a class of endogenous, non-coding small RNAs that negatively regulate gene expression at the post-transcriptional level. Several studies have provided evidence that abnormal expression of selected miRNAs is associated with the pathogenesis of cancer. As they can act as either oncogenes or tumor suppressors, miRNAs have been proposed as potential new therapeutic targets or tools for cancer therapy. Areas covered: This paper reviews a significant body of the experimental data collected to date which indicate that specific miRNA inhibition or replacement can successfully modify the proliferative and invasive properties of tumor cells. It discusses recent evidence that has also revealed a direct involvement of miRNAs in drug resistance, underlying an entirely new mechanism by which tumor cells may be refractory to the treatment with cytotoxic agents. Based on these findings, in the therapeutic setting, interference with cancer-specific miRNAs could be exploited not only to produce a direct anticancer effect but also to improve the response of tumor cells to conventional treatments. Expert opinion: Overall, manipulation of miRNA functions, either by mimicking or inhibiting them, is emerging as a highly promising therapeutic strategy. However, before miRNA-based therapeutics enters the clinical armamentarium, important issues concerning specific delivery to cells/tissues of interest, safety as well as pharmacokinetic profiles needs to be addressed
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