466 research outputs found
I BET on anti-FGFR to fight cancer resistance
No full textGraphical Abstract L. Altucci and R. Benedetti discuss the study by Chua et al (in this issue of EMBO Molecular Medicine), in which co‐targeting of FGFR signaling increases the responses of metastatic uveal melanoma to BET inhibitors
Effects of HDAC inhibitors in human diseases.
No full textContains fulltext :
91753.pdf (Publisher’s version ) (Open Access)Radboud Universiteit Nijmegen, 07 november 2011Promotores : Stunnenberg, H.G., Altucci, L
Deregulation of cell death in cancer: Recent highlights
No full textThe aim of this Special Issue on the deregulation of cell death in cancer is to bring together recent perspectives on the relationship between tumorigenesis and programmed cell death (PCD) [...]
Targeting epigenetic networks with polypharmacology: a new avenue to tackle cancer.
No full textThe term 'epigenetic' fuses old and new concepts that refer to the modulation of gene expression in cellular heritability, fate, development and programming-reprogramming other than the DNA sequence itself. Epigenetic control of transcription is regulated by enzymes that mediate covalent modifications at gene-regulatory regions and histone proteins around which chromosomal DNA is wound. Many of the enzymes that mediate chromatin epigenetic reactions are deregulated in diseases such as cancer. Thus, small-molecule inhibitors that target chromatin-modifying enzymes represent a novel option for treatment, and DNA methyltransferase and histone deacetylase inhibitors have been approved for cancer treatment. Moreover, other classes of epi-enzymes (MS-275, SAHA) have been demonstrated to have strong disease association, and are currently being targeted for modulation. An epigenetic poly-pharmacological approach targeting multiple chromatin-modifying enzymes may represent a 'smart' option to treat cancer versus the current view on the selective and single pharmacological targeting of epigenetic enzymes
Time for Epigenetics
No full textContains fulltext :
75642.pdf (Publisher’s version ) (Closed access)2 p
DNA Mutations via Chern–Simons Currents
No full textWe test the validity of a possible schematization of DNA structure and dynamics based on the Chern–Simons theory, that is a topological field theory mostly considered in the context of effective gravity theories. By means of the expectation value of the Wilson Loop, derived from this analogue gravity approach, we find the point-like curvature of genomic strings in KRAS human gene and COVID-19 sequences, correlating this curvature with the genetic mutations. The point-like curvature profile, obtained by means of the Chern–Simons currents, can be used to infer the position of the given mutations within the genetic string. Generally, mutations take place in the highest Chern–Simons current gradient locations and subsequent mutated sequences appear to have a smoother curvature than the initial ones, in agreement with a free energy minimization argument
Design of dual inhibitors of histone deacetylase 6 and heat shock protein 90
No full textHistone deacetylase 6 (HDAC6) and heat shock protein 90 (Hsp90) are widely investigated anticancer drug targets. Importantly, several lines of evidence indicate that their regulation and activity are intimately linked, and that their combined inhibition may lead to impressive therapeutic benefits. In this study, we developed and applied an integrated computational strategy to design dual inhibitors of HDAC6 and Hsp90. Although the two targets share very little homology, an integrated ligand-based and structure-based virtual screening approach indicated a subset of compounds possessing the key structural requirements for binding at both targets. In vitro tests demonstrated that some of the selected candidates are able to selectively inhibit HDAC6 over HDAC1, to increase the acetylation levels of tubulin on cell assays and to reduce cell proliferation. The discovered compounds represent valuable starting points for further hit optimization
Comment on: LncRNA SBF2-AS1 promotes hepatocellular carcinoma metastasis by regulating EMT and predicts unfavorable prognosis
No full textThe last worldwide evaluation on HCC impact and alarm refer to 20121
with dramatic information in
term of incidence rate and survival outcome. Despite the fact that more than 6 years are passed, the HCC
represents, still nowadays, one of the main oncological diseases in terms of incidence and negative survival
rate with worrying incidence also in many industrialized countries2
. Scientific evidence highlights how
antioxidant3
as well as nutraceutical agents4
can reduce the risk to develop the HCC, but it is not enough in
order to fight its progression and metastasis5
. Several mechanisms of action and markers were discovered
for the HCC6
, laying the foundations of the future innovative therapies and diagnosis approaches. In this
scenario, we read with great interest the article of Zhang et al7
. They evaluated and disseminated the role
of the LncRNA SBF2-AS1 in HCC patients. Starting from patients’ data, they focus on the LncRNA SBF2-
AS1 levels via bioinformatics and qPCR approaches. The data outcome correlates with the SBF2-AS1 up
regulation in HCC. Moreover, the authors investigated the clinical features and prognosis in HCC patients
in correlation with the SBF2-AS1 levels. Vein invasion and TNM stage, together with the low survival rate
strongly correlate with the high levels of LncRNA SBF2-AS1. On the other hands, the suppression of SBF2-
AS1 directly reduces the HCC proliferation and invasion acting on EMT pathway. The Zhang et al7
paper is
oriented towards the new frontiers of precision medicine passing by the patients stratification8
. The final
goal of last decade oncology research aims to provide the right therapy to the right patient9,10.
Concerning the fact the LncRNAs associated with HCC molecular mechanisms is grooving11, the LncRNA
SBF2-AS1 should be considered pivotal for as possible new diagnostic marker and therapy in HCC patient.
Indeed SBF2-AS1 could represent a new source as druggable target able for innovative HCC treatment.
Future studies12 should try to elucidate the potential interplay of mechanism in HCC initiation, progression
and fate among the genetic and epigenetic mechanisms
Gene transactivation and transrepression in myc-driven cancers
No full textMYC is a proto-oncogene regulating a large number of genes involved in a plethora of cellular functions. Its deregulation results in activation of MYC gene expression and/or an increase in MYC protein stability. MYC overexpression is a hallmark of malignant growth, inducing self-renewal of stem cells and blocking senescence and cell differentiation. This review summarizes the latest advances in our understanding of MYC-mediated molecular mechanisms responsible for its oncogenic activity. Several recent findings indicate that MYC is a regulator of cancer genome and epigenome: MYC modulates expression of target genes in a site-specific manner, by recruiting chromatin remodeling co-factors at promoter regions, and at genome-wide level, by regulating the expression of several epigenetic modifiers that alter the entire chromatin structure. We also discuss novel emerging therapeutic strategies based on both direct modulation of MYC and its epigenetic cofactors
- …
