1,721,010 research outputs found
HPV-induced cancers: preclinical therapeutic advancements
Full text linkIntroduction: High-risk HPV infections are related to several epithelial cancers. Despite the availability of prophylactic vaccines, HPV infections are still responsible for about 5% of all human malignancies worldwide. While therapeutic vaccines are ongoing clinical trials, genotoxic agents and surgical interventions represent current clinical treatments, with no specific anti-HPV drugs yet available in the clinics. Areas Covered: We offer a comprehensive report of small molecules in preclinical studies proposed as potential anticancer agents against HPV-driven tumors. Given the importance of HPV oncoproteins for cancer maintenance, particularly E6 and E7, we present a classification of both non-targeted and targeted agents, with a further subdivision of the latter into two categories according to their either direct or indirect activity against viral protein functions. Expert Opinion: Prophylactic vaccines can prevent the insurgence of HPV-related cancers, but have no effect against preexisting infections. Moreover, their high cost, genotype-restricted effect and the growing worldwide distrust for vaccines make the availability of a specific drug an unmet medical need. Different viral early proteins emerge as ideal candidates for drug development. We highlight the most promising strategies and address future challenges in this field to herald the prospect of a specific therapeutic regimen against HPV-related cancers
Antiviral strategies against influenza virus: an update on approved and innovative therapeutic approaches
Full text linkInfluenza viruses still represent a great concern for Public Health by causing yearly seasonal epidemics and occasionally worldwide pandemics. Moreover, spillover events at the animal-human interface are becoming more frequent nowadays, also involving animal species not previously found as reservoirs. To restrict the effects of influenza virus epidemics, especially in at-risk population, and to prepare a drug arsenal for possible future pandemics, researchers worldwide have been working on the development of antiviral strategies since the 80's of the last century. One of the main obstacles is the considerable genomic variability of influenza viruses, which constantly poses the issues of drug-resistance emergence and immune evasion. This review summarizes the approved therapeutics for clinical management of influenza, promising new anti-flu compounds and monoclonal antibodies currently undergoing clinical evaluation, and molecules with efficacy against influenza virus in preclinical studies. Moreover, we discuss some innovative anti-influenza therapeutic approaches such as combination therapies and targeted protein degradation. Given the limited number of drugs approved for influenza treatment, there is a still strong need for novel potent anti-influenza drugs endowed with a high barrier to drug resistance and broad-spectrum activity against influenza viruses of animal origin that may be responsible of future large outbreaks and pandemics
Antiviral drug repurposing: different approaches and the case of antifungal drugs
No full textIn recent years, the emergence of new viruses and the re-emergence of old ones have posed a significant challenge to global Public Health. Viruses characterised by high morbidity and mortality rates have the potential to spread rapidly, causing large epidemic outbreaks and even pandemics. In this context, viral infections still lacking effective treatments represent a serious threat to human health. For this reason, sustained development and implementation of countermeasures are urgently needed against these infections, as they are for diseases for which the emergence of drug resistance is rapidly increasing. In this regard, compared to de novo drug discovery, drug repurposing could represent a highly efficient, faster, and more affordable strategy to develop new drugs. Here, we provide a comprehensive review of the different experimental and computational approaches used for drug repurposing and discuss their advantages and limitations in comparison with other drug discovery strategies. In addition, as an example of the successful application of drug repurposing, we present the case of approved anti-fungal drugs that could be repurposed to counteract viral infections. (c) 2025 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http:// creativecommons.org/licenses/by-nc-nd/4.0/)
Targeted disruption of e6/p53 binding exerts broad activity and synergism with paclitaxel and topotecan against hpv-transformed cancer cells
Full text linkHigh-risk human papillomaviruses (HR-HPV) are the etiological agents of almost all cervical cancer cases and a high percentage of head-and-neck malignancies. Although HPV vaccination can reduce cancer incidence, its coverage significantly differs among countries, and, therefore, in the next decades HPV-related tumors will not likely be eradicated worldwide. Thus, the need of specific treatments persists, since no anti-HPV drug is yet available. We recently discovered a small molecule (Cpd12) able to inhibit the E6-mediated degradation of p53 through the disruption of E6/p53 binding in HPV16-and HPV18-positive cervical cancer cells. By employing several biochemical and cellular assays, here we show that Cpd12 is also active against cervical cancer cells transformed by other HR-HPV strains, such as HPV68 and HPV45, and against a HPV16-transformed head-and-neck cancer cell line, suggesting the possibility to employ Cpd12 as a targeted drug against a broad range of HPV-induced cancers. In these cancer cell lines, the antitumoral mechanism of action of Cpd12 involves p53-dependent cell cycle arrest, a senescent response, and inhibition of cancer cell migration. Finally, we show that Cpd12 can strongly synergize with taxanes and topoisomerase inhibitors, encouraging the evaluation of Cpd12 in preclinical studies for the targeted treatment of HPV-related carcinomas
Estimation of Multivariate Asset Models with Jumps
Full text linkWe propose a consistent and computationally efficient 2-step methodology for the estimation of multidimensional non-Gaussian asset models built using L´evy processes. The proposed framework allows for dependence between assets and different tail-behaviors and jump structures for each asset. Our procedure can be applied to portfolios with a large number of assets as it is immune to estimation dimensionality problems. Simulations show good finite sample properties and significant efficiency gains. This method is especially relevant for risk management purposes such as, for example, the computation of portfolio Value at Risk and intra-horizon Value at Risk, as we show in detail in an empirical illustration
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Dispelling the Myths Behind First-author Citation Counts
Full text linkWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
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