196,097 research outputs found
A network-based bioinformatic analysis for identifying potential repurposable active molecules in different types of human cancers
No full textDrug repurposing, also known as drug repositioning, is the process of identifying novel therapeutic indications for existing drugs, offering a cost-effective and time-efficient strategy to drug discovery. In this context, we developed a network-based algorithm, named SAveRUNNER (Searching off-lAbel dRUg aNd NEtwoRk), which predicts drug-disease associations by accounting for the interaction between the drug targets and disease-associated genes in the human interactome, implementing a novel network-based similarity measure that prioritizes associations between drugs and diseases locating in the same network neighborhoods. Following its successful applications to different disorders (such as viral infections and neurological diseases), in this study, we applied SAveRUNNER on a panel of 13 types of cancers using both disease-associated genes downloaded from widely-used databases and from gene expression data
TCGA2BED: Extracting, extending, integrating, and querying The Cancer Genome Atlas
No full textBackground: Data extraction and integration methods are becoming essential to effectively access and take advantage of the huge amounts of heterogeneous genomics and clinical data increasingly available. In this work, we focus on The Cancer Genome Atlas, a comprehensive archive of tumoral data containing the results of high-throughout experiments, mainly Next Generation Sequencing, for more than 30 cancer types. Results: We propose TCGA2BED a software tool to search and retrieve TCGA data, and convert them in the structured BED format for their seamless use and integration. Additionally, it supports the conversion in CSV, GTF, JSON, and XML standard formats. Furthermore, TCGA2BED extends TCGA data with information extracted from other genomic databases (i.e., NCBI Entrez Gene, HGNC, UCSC, and miRBase). We also provide and maintain an automatically updated data repository with publicly available Copy Number Variation, DNA-methylation, DNA-seq, miRNA-seq, and RNA-seq (V1,V2) experimental data of TCGA converted into the BED format, and their associated clinical and biospecimen meta data in attribute-value text format. Conclusions: The availability of the valuable TCGA data in BED format reduces the time spent in taking advantage of them: it is possible to efficiently and effectively deal with huge amounts of cancer genomic data integratively, and to search, retrieve and extend them with additional information. The BED format facilitates the investigators allowing several knowledge discovery analyses on all tumor types in TCGA with the final aim of understanding pathological mechanisms and aiding cancer treatments
TRATTAMENTO CON ESTRADERM TTS 50. FOLLOW-UP CON TERMOGRAFIA A CONTATTO
No full textLa termografia,attento indice delle attività biologico-funzionali dei tessuti,è in grado di seguire puntualmente tutti i fenomeni che si verificano a carico della mammella.Quindi sono stati valutati gli effetii sulla ghiandola mammaria della terapia sostitutiva estroprogestinica
Role of the long non-coding RNA PVT1 in the dysregulation of the ceRNA-ceRNA network in human breast cancer
No full textRecent findings have identified competing endogenous RNAs (ceRNAs) as the drivers in many disease conditions, including cancers. The ceRNAs indirectly regulate each other by reducing the amount of microRNAs (miRNAs) available to target messenger RNAs (mRNAs). The ceRNA interactions mediated by miRNAs are modulated by a titration mechanism, i.e. large changes in the ceRNA expression levels either overcome, or relieve, the miRNA repression on competing RNAs; similarly, a very large miRNA overexpression may abolish competition. The ceRNAs are also called miRNA decoys or miRNA sponges and encompass different RNAs competing with each other to attract miRNAs for interactions: mRNA, long non-coding RNAs (lncRNAs), pseudogenes, or circular RNAs. Recently, we developed a computational method for identifying ceRNA-ceRNA interactions in breast invasive carcinoma. We were interested in unveiling which lncRNAs could exert the ceRNA activity. We found a drastic rewiring in the cross-talks between ceRNAs from the physiological to the pathological condition. The main actor of this dysregulated lncRNA-associated ceRNA network was the lncRNA PVT1, which revealed a net biding preference towards the miR-200 family members in normal breast tissues. Despite its up-regulation in breast cancer tissues, mimicked by the miR-200 family members, PVT1 stops working as ceRNA in the cancerous state. The specific conditions required for a ceRNA landscape to occur are still far from being determined. Here, we emphasized the importance of the relative concentration of the ceRNAs, and their related miRNAs. In particular, we focused on the withdrawal in breast cancer tissues of the PVT1 ceRNA activity and performed a gene expression and sequence analysis of its multiple isoforms. We found that the PVT1 isoform harbouring the binding site for a representative miRNA of the miR-200 family shows a drastic decrease in its relative concentration with respect to the miRNA abundance in breast cancer tissues, providing a plausibility argument to the breakdown of the sponge program orchestrated by the oncogene PVT1. © 2017 Conte et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited
Rubella susceptibility profile in pregnant women with HIV
No full textData on susceptibility, assessed through serological testing or personal history, were analyzed with respect to several demographic and HIV-related characteristics. Following exclusion of 93 women with rubella status reported as unknown, 1146 pregnancies with a live birth were analyzed.
Overall, between 2001 and 2009, 303 women (26.4%) were reported as susceptible. Among the 843 nonsusceptible women, 163 (19.3%) were reported as previously vaccinated, with a significant increase during the study period in the proportion of vaccinated women, from 3.4% in 2001 to 25.0% in 2009 (χ2 for trend: P < .001). During the same period, the proportion of susceptible women decreased significantly, from 26.9% in 2001 (36.2% in 2002) to 18.8% in 2009 (P = .002).
The general characteristics of susceptible and nonsusceptible women are reported in Table 1. Rubella susceptibility was not associated with any particular HIV-related or demographic characteristic, but appeared to be significantly associated with susceptibility to Toxoplasma infection (odds ratio [OR]: 3.10, 95% confidence interval [CI]: 2.24–4.29, P < .001) and with susceptibility to cytomegalovirus (CMV) infection (OR, 6.90; 95% CI, 5.06–9.14; P < .001), with a borderline-significance association (P = .063) with a negative history of sexually transmitted infections [STI] (OR, 1.49; 95% CI, .98–2.29).
View this table:
In this windowIn a new windowTable 1.
Characteristics Of Pregnant Women With and Without Rubella Susceptibility
Overall, among 1011 children with available information on birth defects, no cases of CRS were observed. The overall birth defect rate (3.4%; 95% CI, 2.3–4.5) was similar to other studies on HIV infection [4, 5]. Only 2 women (.19%) were positive for rubella IgM antibodies during pregnancy (at 16 and 30 wk of pregnancies, respectively). In both cases, children had no birth defects or functional abnormalities.
In our cohort, which collects, based on HIV seroprevalence data [6], no less than 40% of deliveries in HIV-infected women in Italy, about 20% of HIV-infected pregnant women appear to be currently susceptible to rubella infection. This proportion is high compared with other studies on rubella seroprevalence in Italy [7] and suggests higher susceptibility rate and lower frequency of vaccination among women with HIV. It is unknown to what extent concerns about using a live attenuated vaccine in women with HIV may be responsible for the low frequency of vaccination observed. However, in our sample, only a limited proportion of women had low CD4 count or clinically relevant immunosuppression that may have prevented vaccination. The significant reduction in the rate of susceptibility during the last decade, coupled with the concurrent significant increase in the proportion of vaccinated women, is encouraging and suggests that a further decline in rubella susceptibility can be obtained in this population using appropriate vaccination strategies. Our data also suggest that susceptibility to rubella is associated to susceptibility to other infections that may be responsible for congenital syndromes or newborn infections (Toxoplasma, CMV, or sexually transmitted infection), and as such reinforce the need for an appropriate preconception counseling and care in this particular population.
Next SectionAcknowledgments
The Italian Group on Surveillance on Antiretroviral Treatment in Pregnancy
Project coordinators: M. Floridia, M. Ravizza, E. Tamburrini.
Investigators: M. Ravizza, E. Tamburrini, F. Mori, P. Ortolani, E.R. dalle Nogare, G. Sterrantino, M. Meli, S. Polemi, J. Nocentini, M. Baldini, G. Montorzi, M. Mazzetti, B. Borchi, F. Vichi, E. Pinter, E. Anzalone, R. Marocco, C. Mastroianni, V.S. Mercurio, A. Carocci, E. Grilli, A. Maccabruni, B. Mariani, A. Moretti, G. Natalini, G. Guaraldi, K. Luzi, G. Nardini, C. Stentarelli, A. Degli Antoni, A. Molinari, P. Rogasi, M.P. Crisalli, A. Donisi, M. Piepoli, V. Cerri, A. Viganò, V. Giacomet, V. Fabiano, S. Stucchi, C. Cerini, G. Placido, M. D'Alessandro, A. Vivarelli, P. Castelli, F. Savalli, V. Portelli, F. Sabbatini, D. Francisci, S. Alberico, G. Maso, M. Tropea, A. Meloni, D. Gariel, C. Cuboni, F. Ortu, P. Piano, A. Citernesi, I. Vicini, E. Periti, A. Spinillo, M. Roccio, A. Vimercati, E. Bassi, B. Guerra, F. Cervi, E. Tridapalli, G. Brighi, M. Stella, G. Faldella, C. Puccetti, M. Sansone, P. Martinelli, A. Agangi, C. Tibaldi, L. Trentini, S. Marini, G. Masuelli, I. Cetin, A. Crepaldi, M.L. Muggiasca, E. Ferrazzi, C. Giaquinto, M. Fiscon, R. Rinaldi, E. Rubino, A. Bucceri, R. Matrone, G. Scaravelli, G. Anzidei, C. Fundarò, O. Genovese, C. Cafforio, C. Pinnetti, G. Liuzzi, V. Tozzi, P. Massetti, M. Anceschi, A.M. Casadei, F. Montella, A.F. Cavaliere, V. Finelli, C. Riva, L. Lazier, M. Cellini, S. Garetto, G. Castelli Gattinara, A.M. Marconi, S. Foina, S. Dalzero, M. Moneta, F. Di Lorenzo, C. Polizzi, A. Mattei, M.F. Pirillo, R. Amici, C.M. Galluzzo, S. Donnini, S. Baroncelli, M. Floridia.
Pharmacokinetics: M. Regazzi, P. Villani, M. Cusato.
Advisory Board: A. Cerioli, M. De Martino, P. Mastroiacovo, M. Moroni, F. Parazzini, E. Tamburrini, S. Vella.
SIGO-HIV Group National Coordinators: P. Martinelli, M. Ravizza.
We thank all the women who participated in the study, Cosimo Polizzi and Alessandra Mattei for technical support to the project, and Maria Cristina Rota and Pierpaolo Mastroiacovo for their help in discussing the manuscript and the data.
Financial support. This work was supported by the Italian National Program on Research on AIDS (public grants 39C/A, 31D55, and 31D56); and the Italian Medicines Agency (AIFA; public research grants). No funding was received for this work from any of the following organizations: National Institutes of Health (NIH); Wellcome Trust; and the Howard Hughes Medical Institute (HHMI).
Potential conflicts of interest. All authors: no conflicts.
© The Author 2011. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: [email protected].
Previous Section References
1.↵Duszak RS. Congenital rubella syndrome-major review. Optometry 2009;80:36-43.
Medline2.↵Nardone A, Tischer A, Andrews N, et al. Comparison of rubella seroepidemiology in 17 countries: Progress towards international disease control targets. Bull World Health Organ 2008;86:118-25.
CrossRefMedlineWeb of Science3.↵Floridia M, Ravizza M, Tamburrini E, et al. Diagnosis of HIV infection in pregnancy: Data from a national cohort of pregnant women with HIV in Italy. Epidemiol Infect 2006;134:1120-7.
Medline4.↵Antiretroviral Pregnancy Registry Steering Committee. Antiretroviral pregnancy Registry international Interim Report for 1 January 1989 – 31 January 2010. Wilmington, NC: Registry Coordinating Center; 2010. Available at: www.APRegistry.com. Accessed 19 November 2010.
5.↵Townsend C, Willey B, Cortina-Borja M, Peckham C, Tookey P. Antiretroviral therapy and congenital abnormalities in infants born to HIV-infected women in the UK and Ireland, 1990–2007. AIDS 2009;23:519-24.
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CrossRefMedlineWeb of Science7.↵Rota MC, Bella A, Gabutti G, et al. Rubella seroprofile of the Italian population: An 8-year comparison. Epidemiol Infect 2007;135:555-62.
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Clin Infect Dis. (2011) 52 (7): 960-962.
doi: 10.1093/cid/cir040
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