1,720,999 research outputs found
HDAC inhibitors as epigenetic regulators for cancer immunotherapy
No full textIn recent years, anti-tumor immunotherapy has shown promising results, and immune-oncology is now emerging as the fourth major wave in the treatment of tumors after radiotherapy, chemotherapy and molecular targeted therapy. Understanding the impact of the immune system on neoplastic cells is crucial to improve its effectiveness against cancer. The stratification of patients who might benefit from immunotherapy as well as the personalization of medicine have contributed to the discovery of new immunotherapeutic targets and molecules. In the present review, we discuss the mechanistic role of histone deacetylase inhibitors (HDACi) as potential immunomodulating agents to treat cancer. Our current understanding of the use of HDACi in combination with various immunotherapeutic approaches, such as immunomodulating agents and cancer vaccines, is also addressed. The potential clinical applications of the growing number of novel epigenetic drugs for cancer immunotherapy are widening, and some of these therapies are already in clinical trials
Recent Advancement in Anticancer Compounds from Marine Organisms: Approval, Use and Bioinformatic Approaches to Predict New Targets
No full textIn recent years, the study of anticancer bioactive compounds from marine sources has received wide interest. Contextually, world regulatory authorities have approved several marine molecules, and new synthetic derivatives have also been synthesized and structurally improved for the treatment of numerous forms of cancer. However, the administration of drugs in cancer patients requires careful evaluation since their interaction with individual biological macromolecules, such as proteins or nucleic acids, determines variable downstream effects. This is reflected in a constant search for personalized therapies that lay the foundations of modern medicine. The new knowledge acquired on cancer mechanisms has certainly allowed advancements in tumor prevention, but unfortunately, due to the huge complexity and heterogeneity of cancer, we are still looking for a definitive therapy and clinical approaches. In this review, we discuss the significance of recently approved molecules originating from the marine environment, starting from their organism of origin to their structure and mechanism of action. Subsequently, these bio-compounds are used as models to illustrate possible bioinformatics approaches for the search of new targets that are useful for improving the knowledge on anticancer therapies
Marine-Derived Secondary Metabolites as Promising Epigenetic Bio-Compounds for Anticancer Therapy
Full text linkSessile organisms such as seaweeds, corals, and sponges continuously adapt to both abiotic and biotic components of the ecosystem. This extremely complex and dynamic process often results in different forms of competition to ensure the maintenance of an ecological niche suitable for survival. A high percentage of marine species have evolved to synthesize biologically active molecules, termed secondary metabolites, as a defense mechanism against the external environment. These natural products and their derivatives may play modulatory roles in the epigenome and in disease-associated epigenetic machinery. Epigenetic modifications also represent a form of adaptation to the environment and confer a competitive advantage to marine species by mediating the production of complex chemical molecules with potential clinical implications. Bioactive compounds are able to interfere with epigenetic targets by regulating key transcriptional factors involved in the hallmarks of cancer through orchestrated molecular mechanisms, which also establish signaling interactions of the tumor microenvironment crucial to cancer phenotypes. In this review, we discuss the current understanding of secondary metabolites derived from marine organisms and their synthetic derivatives as epigenetic modulators, highlighting advantages and limitations, as well as potential strategies to improve cancer treatment
HDAC2-dependent miRNA signature in acute myeloid leukemia
No full textAcute myeloid leukemia (AML) arises from a complex sequence of biological and finely orchestrated events that are still poorly understood. Increasingly, epigenetic studies are providing exciting findings that may be exploited in promising and personalized cutting-edge therapies. A more appropriate and broader screening of possible players in cancer could identify a master molecular mechanism in AML. Here, we build on our previously published study by evaluating a histone deacetylase (HDAC)2-mediated miRNA regulatory network in U937 leukemic cells. Following a comparative miRNA profiling analysis in genetically and enzymatically HDAC2-downregulated AML cells, we identified miR-96-5p and miR-92a-3p as potential regulators in AML etiopathology by targeting defined genes. Our findings support the potentially beneficial role of alternative physio-pathological interventions. This article is protected by copyright. All rights reserved
Editorial: chemical innovative approaches in cancer molecular medicine and translational clinical research
Full text linkCancer is considered a multifactorial pathology, whose understanding involves genomic and epigenomic studies supplemented by biochemical, biological, molecular, and epidemiological data. Current cancer research strategies are based on the paradigm of “targeted” therapies. Targeted cancer therapies are drugs or other substances that block the growth and spread of cancer by interfering with specific molecules (“molecular targets”) that are involved in growth, progression, and spread of cancer. Many targeted cancer therapies have been approved by the Food and Drug Administration (FDA) to treat specific types of cancer. Others are being studied in advanced clinical trials, and many more are in preclinical and clinical testing. Despite recent progress in regression or control for a wide variety of tumors, some cancers do not respond to current therapeutic patterns, showing limited 5-year survival rates, high recurrence, and frequent relapse and metastases, making them big killers. Indeed, combined efforts between biologists, chemists, and oncologists are required to provide novel therapeutic options for patients and to achieve precision medicine based on the molecular integrated metabolic and (epi)genome signature.
A big deal of results has been published regarding cancers and their treatments, thus representing a very prosperous area of drug discovery. Despite the significant amount of drug discoveries in the vast field of cancer therapy, there is still an urgent need for novel and innovative treatments. Efficacy and safety of the therapy are a major concern and significant advances in structural biology and bioinformatics in the last 20 years gave medicinal chemists a well-filled toolbox for the design of innovative drugs using the most advanced techniques working closely together with biochemists, biologists, and other medical-related researchers to develop next generation anticancer therapies. In the present special issue, various aspects of modern approaches in cancer therapy have been either summarized in comprehensive review articles or published as original articles
Forskolin potentiates the effects of GSKJ4 in human acute myeloid leukemia cells through Protein Kinase A pathway
No full textForskolin is a natural cAMP elevating agent that is emerging as one of the most promising molecules for its potential use in cancer therapy. The epigenetic marks play a relevant role in several cancer types, including in leukemia. In particular, GSKJ4 has been recently demonstrated to act as a potent proliferation inhibitor in many tumor cell lines. Due to the failure of the single agent therapy, recently the chemotherapy combination has received more attention in order to increase the therapeutic index and to reduce the side effects. In this scenario, naturally occurring molecules represent the ideal candidates to investigate cooperative responses with conventional and new antineoplastic drugs. Here, we investigate the capability of forskolin to potentiate the effects of GSKJ4 in human leukemia U937 cells. We provide evidence that forskolin markedly sensitizes GSKJ4-induced antiproliferative effects through apoptosis induction (caspase-3 activation and PARP cleavage). In addition, we demonstrate that this phenomenon is mediated by cAMP elevation and Protein Kinase A (PKA) involvement, as indicated by the use of PKA inhibitor (KT-5720). In conclusion, our findings provide initial evidence about the efficacy of forskolin/GSKJ4 combination in leukemia cells and suggest a new possible therapeutic approach for AML treatment
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
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