Дисертації з теми "HDIC"
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Toffoli, Valeria. "Superhydrophobic BIOMEMS sensor arrays: development of actuation and readout electronic strategies." Doctoral thesis, Università degli studi di Trieste, 2014. http://hdl.handle.net/10077/9993.
Повний текст джерелаLa tecnologia dei sistemi micro-elettro-meccanici (MEMS) ha dimostrato d’avere grandi potenzialità in molti campi, in particolare nei sistemi bio-medicali. Essa si basa infatti su processi di fabbricazione ad altro volume produttivo, permettendo una considerevole riduzione dei costi per dispositivo. Un ulteriore beneficio di questa tecnologia risiede nella possibilità di dimensionare i dispositivi fino a raggiungere l’ordine del submicron, così da consentire l’integrazione e il monitoraggio in tempo reale di sistemi sensibili a biomarker di tipo medicale e biologici. Tra gli obiettivi futuri dei MEMS biomedicali (BioMEMS) vi è la realizzazione di dispositivi in grado di interfacciarsi direttamente con il paziente e definirne lo stato di salute grazie alla rilevazione del livello di centinaia di diversi biomarker (siano essi chimici o fisici). La medicina assumerebbe in questa visione una configurazione ad personam nella quale al paziente verrebbe prontamente somministrato un quantitativo di medicinale adatto alle risposte del suo organismo. A tale scopo i dispositivi MEMS devono essere in grado di effettuare analisi multiple operando in un ambiente liquido. Tuttavia è proprio l’ambiente liquido a comportare la riduzione di sensibilità e, quindi, di performance dei sensori MEMS. La presente ricerca si pone lo scopo di sviluppare nuovi sistemi elettronici di misurazione e attuazione di due distinte tipologie di BioMEMS risonanti operanti in liquido, i cantilever e i pillar. In particolare verrano trattati tre argomenti: la realizzazione di setup ottici per applicazione dei MEMS in liquido ed in aria, la progettazione di sistemi elettronici di attuazione e lettura di singoli pillar nel loro comportamento in frequenza e lo sviluppo di un software LabVIEW in grado di programmare un FPGA ed ottenere un PLL digitale da impiegarsi nell’analisi in tempo reale del comportamento in frequenza di RF-MEMS. Il primo progetto è stato sviluppato in collaborazione l'Università di Kaiserslautern (Germania) e prevedeva la realizzazione di sistemi microfluidici e setups ottici, interfacciati in modo tale da permettere la rilevazione della risposta in frequenza di molteplici MEMS operanti in parallelo. Nel secondo progetto l’obiettivo era la realizzazione di un sistema elettronico in grado di integrare in un unico dispositivo i sistemi di attuazione e lettura dei pillar. In particolare siamo stati in grado di modulare l’ampiezza di risonanza dei nostri dispositivi risonanti mediante l’applicazione della forza di polarizzazione Kelvin mentre lo sviluppo del sistema di lettura richiede ulteriore lavoro di indagine. Infine, nell'ultimo progetto è stato realizzato un sistema PLL digitale con 10 MHz di banda passante utilizzando la tecnologia della National Instruments (FlexRIO NI5781R). Mediante questo PLL si è potuto identificare la frequenza di risonanza di diverse tipologie di MEMS e se ne è seguite le variazioni in tempo reale . Le attività di ricerca sperimentale sono state eseguite presso il laboratorio CNR- IOM a Trieste.
XXVI Ciclo
1985
Zagni, Chiara. "Progettazione e sintesi di nuovi inibitori delle istone deacetilasi." Thesis, Università degli Studi di Catania, 2011. http://hdl.handle.net/10761/253.
Повний текст джерелаThe epigenetic control of gene expression is operated through post-translational modifications of chromatin such as acetylation and deacetylation. Two enzymes are responsable for these processes: HAT (histone acetyl transferase) and HDAC (histone deacetylase). HDAC is a group of enzymes involved in regulating gene expression, DNA repair and stress response. Acetylation plays an important role in trascription because it remodels chromatin structure enhancing access to DNA-binding factors. In general, increased levels of histone acetylation are associated with increased transcriptional activity, whereas decreased levels of acetylation are associated with repression of gene expression. In tumor cells abnormal gene expression is frequently observed. HDAC inhibitors have been shown to be potent inducers of growth arrest, differentiation, and apoptotic cell death both in vitro and in vivo transformed cells. To date there are seven distinct classes of HDAC inhibitors and all contain three key structural elements to their pharmacophore: a) a zinc-binding group which coordinates the zinc ion at the bottom of the long narrow active site cavity; b) a capping group which interacts both with the amino acids on the rim of the binding cavity and the protein surface; c) a linker domain whose role is to ensure the correct positioning of the two former groups and to in-teract with the lipophilic binding tunnel. Following our recent interest in the research of more potent HDAC inhibitors, we have projected and synthesized a new series of compounds containing four new zinc chelant moieties, i.e. formylhydrazonomethyl, 2-formylhydrazinocarbonyl, 2,2,2-trifluoro-N-methylideneacetamidic and N-(trifluoroacetyl)amidic, linked by an aromatic spacer to an aromatic sulfonamide, that is responsible of hydrophobic interaction with HDAC. Docking studies have shown that these new molecules fit very good in the HDAC enzymatic pocket with a best ï Gbind of â 7,9 kcal/mol that is 1 kcal/mol lower of the corresponding one for SAHA, a good HDAC.
Ozdarska, Katarzyna. "Synthèses d’inhibiteurs de HDAC et leurs tests biologiques (Cytotoxicité, HDAC inhibition)." Thesis, Reims, 2020. http://www.theses.fr/2020REIMS023.
Повний текст джерелаEpigenetics represents changes in gene expression without altering the nucleic sequence of DNA. One of the main mechanisms of regulation of gene expression is chromatin remodeling via histone acetyltransferases and histone deacetylases (HDAC), which may or may not allow gene transcription. An abnormal expression of HDACs is correlated with many diseases (alcohol dependence, inflammation as well as cardiovascular and neurodegenerative diseases, cancers...). It is essential to target the selectivity of one isoform among the 11 known zinc-dependent HDACs to avoid side effects. The aim of the research was to design and synthesize new compounds, verify their inhibitory activity against class I or II HDACs and their cytotoxicity on four cell lines: HaCaT, V79-4, SH-SY5Y and PC12. We focused on the pharmacomodulations of ZBG, the linker and the cap of known molecules such as MS-275 (selective for class I of HDACs), SAHA and TSA (spacer in C5 or C6) with a strong inhibitory activity towards HDACs, but not selective. We concentrated on the pharmacomodulations of known HDACI modifying the zinc binding domain (sulfonylhydrazide, catechol), the nature of the spacer (alkyl, aryl) and the surface recognition group (bis-aryl, adamantyl, indolopyridazinone). A library of 57 new compounds was designed in three series. None of them showed satisfactory inhibitory activity. The selected compounds did not show cytotoxic activity on neuronal cell lines. Based on this research, it is possible to create new compounds in the indolopyridazinone series in order to test them
Khan, Omar Ali. "HR23B, a biomarker for HDAC inhibitors." Thesis, University of Oxford, 2013. http://ora.ox.ac.uk/objects/uuid:9cd76c0b-e70e-43f7-a92d-a99f403a077e.
Повний текст джерелаPolášek, Jaromír. "Implementace protokolu HDLC v síťových simulátorech." Master's thesis, Vysoké učení technické v Brně. Fakulta elektrotechniky a komunikačních technologií, 2018. http://www.nusl.cz/ntk/nusl-377008.
Повний текст джерелаSchreiner, Lindsay Marie. "HDAC Mediated Integration of NF-¿B Transcriptional Regulation." University of Toledo / OhioLINK, 2014. http://rave.ohiolink.edu/etdc/view?acc_num=toledo1404744801.
Повний текст джерелаAlqahtani, Abdulateef Alqarni. "Synthesis and Biological Evaluation of New HDAC Inhibitors." University of Toledo / OhioLINK, 2018. http://rave.ohiolink.edu/etdc/view?acc_num=toledo1525448898248748.
Повний текст джерелаSindi, Shaimaa Hesham. "Guanidine- Based HDAC-Inhibitors as Anti-Cancer Agents." University of Toledo / OhioLINK, 2019. http://rave.ohiolink.edu/etdc/view?acc_num=toledo1564676186975875.
Повний текст джерелаPerin, Stefano <1995>. "Sintesi di inibitori peptidici per interazione MEF2-HDAC." Master's Degree Thesis, Università Ca' Foscari Venezia, 2021. http://hdl.handle.net/10579/19004.
Повний текст джерелаSodji, Quaovi Hemeka. "Improving histone deacetylase inhibition therapy through isoform selectivity and targeted delivery." Diss., Georgia Institute of Technology, 2014. http://hdl.handle.net/1853/53445.
Повний текст джерелаDlamini, Samkeliso Mpendulo Dlamini. "Synthesis and Biological Evaluation of HDAC Inhibitors with 1-(1H-imidazol-2-yl)ethan-1-one Moiety as the Metal-Binding Group." University of Toledo / OhioLINK, 2017. http://rave.ohiolink.edu/etdc/view?acc_num=toledo1501770195684609.
Повний текст джерелаLee, Daniel T. (Daniel Tzonglin) 1974. "Configurable byte-wide HDLC controller supporting IP over SONET." Thesis, Massachusetts Institute of Technology, 1998. http://hdl.handle.net/1721.1/47577.
Повний текст джерелаSiqueira, Denise de 1975. "Construção de espaços de elementos finitos do tipo Hdiv." [s.n.], 2012. http://repositorio.unicamp.br/jspui/handle/REPOSIP/306356.
Повний текст джерелаTese (doutorado) ¿ Universidade Estadual de Campinas, Instituto de Matemática, Estatística e Computação Científica
Made available in DSpace on 2018-08-19T19:19:39Z (GMT). No. of bitstreams: 1 Siqueira_Denisede_D.pdf: 19845716 bytes, checksum: dbcb91683ea323e390eb0dc4a89e18c3 (MD5) Previous issue date: 2012
Resumo: O estudo do presente trabalho se enquadra na área de Análise Numérica para equações diferenciais utilizando o método de elementos finitos. Especificamente, o objetivo é a construção de espaços de elementos finitos vetoriais Hdiv-conformes. Em formulações mistas de problemas elípticos, que consistem em resolver, simultaneamente, tanto a variável primal p quanto a sua variável dual gradiente de p, espaços do tipo Hdiv são utilizados para aproximar a variável dual. A principal característica de espaços Hdiv-conformes é a continuidade da componente normal nas interfaces dos elementos. Para garantir este comportamento, propõe-se uma sistemática de construção baseada na definição de um campo vetorial ajustado a geometria da partição do domínio, combinada com funções de base escalares H1conformes disponíveis na literatura. Com esta metodologia, são construídas bases hierárquicas, de ordem arbitrária, para subespaços Hdiv-conformes em partições triangulares ou quadrilaterais bidimensionais. No entanto, na simulação de problemas elípticos pela formulação mista, os espaços envolvidos na aproximação das variáveis dual e primal necessitam ser compatíveis para garantir a estabilidade do método. Neste sentido, os espaços desenvolvidos são ajustados de forma a obter taxas ótimas de convergência em um problema de autovalor de Steklov. Considera-se também o acoplamento de formulações clássica e mista para um problema elíptico, no contexto de decomposição de domínios, em que as bases Hdiv-conformes compatibilizadas são aplicadas na formulação mista correspondente
Abstract: The study of this work fits in the area of numerical analysis for differential equations using the finite element method. Specifically, the goal is to construct Hdiv-conformes vectorial finite element spaces. In the mixed formulations of elliptic problems, where the principle is to solve simultaneously both the variable primal p as its dual variable gradient of p, Hdiv spaces are used to approximate the dual variable. The main feature spaces Hdiv-conformes is the continuity of the normal component at the interfaces of elements. To ensure this behavior, we propose a systematic construction based on the definition of a vector field adjusted to the geometry of the domain partition, combined with scalar basis functions H1-conformes available in the literature. With this methodology, hierarchical bases are constructed of arbitrary order, for subspaces Hdiv-conforming considering partitions in two-dimensional triangular or quadrilateral elements. However, the simulation of elliptic problems by the mixed formulation, the spaces involved in the approximation of the primal and dual variables need to be compatible to ensure the stability of the method. In this sense, the approximations spaces are adjusted to obtain optimal rates of convergence for a Steklov eigenvalue problem. It is also consider the coupling of classical and mixed formulations for an elliptical problem in the context of domain decomposition, which the compatibilized bases Hdiv-conformes are applied to the corresponding mixed formulation
Doutorado
Matematica Aplicada
Doutor em Matemática Aplicada
Stavropoulou, Alexandra Vassiliki. "Histone deacetylase (HDAC) inhibitors and FBXL20 in breast cancer." Thesis, Imperial College London, 2008. http://hdl.handle.net/10044/1/7389.
Повний текст джерелаLinares, Aurélien. "Histone désacétylases, signalisation œstrogénique et cancer du sein : établissement d’outils bioluminescents pour la détection d’inhibiteurs sélectifs de HDAC : expression et rôle de HDAC9 dans les lignées cellulaires de cancer du sein." Thesis, Montpellier 1, 2011. http://www.theses.fr/2011MON13504/document.
Повний текст джерелаThe estrogen receptor (ER) can modulate the gene expression with consequences in the cell proliferation, apoptosis. This modulation is possible by the recruitment of coactivator or corepressor complexes. The repression activity is in particular explained by the histones deacetylases (HDACs). This protein family is composed by eighteen members who have been classified in four groups. These HDACs are subdivided on structural and functional similarities. The class I isoforms (HDACs 1, 2, 3 and 8), class II (HDACs 4, 5, 6, 7, 9, 10) and class IV (HDAC11) are Zn-dependent enzymes, whereas class III HDACs (Sirtuins 1-7) are NAD+-dependent. Recent data from the laboratory have shown, at the mRNA level, there is an enormous expression differential of HDAC9 between breast cancer cell line ER positive and negative or OHT resistant cell line. During my thesis, I demonstrated that the regulations of the HDAC9 on the level of its expression as of its role in the various breast cancer cell lines were implicated in the estrogen signaling. This regulation takes place at the transcriptional level and in the ERet#945; activity.In addition, using broad spectrum HDAC inhibitors (HDIs) such as TSA (Tricostatin A), many studies have shown that these inhibitors had antiangiogenic activity. Thus, the design or the identification of selective and potent HDAC inhibitors as agents anti-tumoral and/or anti-metastatic can emerge in a novel opportunity used alone or in combination with the already existing agents for the treatment of cancers. In order to identify and characterize new HDIs, my thesis works consisted to establish bioluminescent cell lines for screening HDAC inhibitors. Different cell GAL4-VP16-HDACs chimeras' models were generated to determine the selectivity of HDIs for the different HDACs
Kulkarni, Upendra M. "Performance analysis of HDLC protocol operating in asynchronous balanced mode." Thesis, Virginia Tech, 1988. http://hdl.handle.net/10919/45897.
Повний текст джерелаThe objective of this work is to analyze the performance of HDLC Balanced Class of
Procedures under saturated, full-duplex transmission on error prone links. This thesis
extends work done by Bux et al. [8] by considering errors on both the links. Satellite
links have long propogation delays compared to terrestrial links, and hence, have
longer error recovery times. For such links, errors in acknowledgements have considerable
impact on the throughput. In this analysis, the effect of errors in acknowledgements
is taken in to consideration. An analytical approach is used to derive
performance measures. The concept of "virtual transmission time" introduced by Bux
et al is redefined to accommodate the effect of errors in acknowledgements and
used in the analysis. Resulting throughput calculations show how various parameters,
(e.g. transmission rate, propagation delay, error rate and packet size), interact
and determine the performance.
Master of Science
Regna, Nicole Lynn. "Isoform-Selective HDAC Inhibition for the Treatment of Lupus Nephritis." Diss., Virginia Tech, 2014. http://hdl.handle.net/10919/49023.
Повний текст джерелаPh. D.
Manzo, Fabio. "Functional regulation of class II HDAC trough their catalytic inhibition." Université Louis Pasteur (Strasbourg) (1971-2008), 2008. http://www.theses.fr/2008STR13159.
Повний текст джерелаHuman HDACs comprise a family of 18 different members which are grouped into four classes. Class I (HDAC 1-3,8), class II (HDAC4-7,9,10 of which HDAC4, 5, 7 and 9 form a class II a subgroup due to a common structural organization, while HDAC6 is member of class IIb), class III, also referred to as sirtuins (SIRT1-7) and class IV (HDAC11). Classes I, II and IV HDACs share common features, as all their members are zinc-dependent and exhibit some sequence similarities, while class III HDACs are NAD+-dependent enzymes without homology the other HDACs(1). Pan-inhibitors like SAHA, which is currently in phase III clinical trials and has recently been approved for treatment of cutaneous T cell lymphoma, inhibit both classes I and II enzymes, while MS275 is a subclass I selective inhibitor, which blocks the activities of HDAC 1, 2 and much less efficiently HDAC 3. Also class II selective inhibitors have been generated, marking the onset of a dissection of the various activities of HDACs. Notably, while induction of TRAIL appears to be associated with inhibition of class I enzymes in cancerous systems, other cellular functions involve the action of class II HDACs, like the regulation of the differentiation, mainly the cardiac differentiation. In differentiation systems: C2C12 cells, F9 cells, 3T3L1 cells. We tested a new compound HDAC inhibitor, specific for HDAC class 2 in one leukemic model, U937 cells, and various differentiation systems, such as the C2C12 cells for muscle differentiation, the F9 cells for endodermal differentiation and 3t3l1 cells for adypocyte differentiation. Interestingly we found that in C2C12 cells the HDAC class 2 inhibitor blocked the catalytic action of the HDAC class 2, but stabilized the interaction between the transcriptional factor MEF2D and HDAC4. MEF2D is the main transcriptional factor, responsible for the terminal muscle differentiation, and its transcriptional activity inhibition consequently blocked the muscle differentiation. In a similar way in both the other two systems we evaluated the differentiation inhibition and we found that transcriptional activity of RAR and PPARγ, respectively essential for the differentiation of the two systems, was blocked either in vitro in the first case either in vivo in the second case. In the case of the PPARγ induced differentiation, the experiments were assayed in the 3T3L1 cells. The treatment of these cells with Troglitazone induced adypocyte differentiation, while the presence of the MC1568 blocked it completely. Analyzing the Pparg’s expression level for RT-PCR, we found that its level was highly decreased after treatment with the MC1568. Interestingly the treatment of a mouse stably expressing a PPRE-luc, PPAR responsive elements luciferase reporter, blocked the transcriptional activity of PPARγ, showing in this case that the compound was regulating both the nuclear receptor’s transcriptional activity and the transactivation. In tumour model: MCF7 cells In cancer systems, such as MCF7 cells we found that the HDAC class 2 inhibitor MC1568 was inducing HDAC4 sumoylation, that, as previously showed (2) increases the HDAC4 catalytic action. The transfection of a specific HDAC4 sumoylation mutant in F9 cells decreased the repressory power on a note RAR target gene, Collagen IV. We were able to demonstrate that the treatment with MC1568 was regulating the activity of two transcriptional factor, RAR alpha and NF-KB, on three target genes, IRF1, TNF and TRAIL. The HDAC4 sumoylation mediated by RANBP2 repressed transiently the expression of these target genes, that were up-regulated after the complete degradation of HDAC4. Acute promyelocitic leukemia (APL), NB4 cells The NB4 cells is a cellular system of acute promyelocitic leukemia (APL). This disease is characterized by the presence of a fusion protein, PMLRAR alpha, with a strong repressory activity, mediated by the enhanced recruitment of corepressory complexes. The patients are treated with the differentiation therapy with retinoic acid (ATRA). Even if it is quite efficient to treat it, it still remains the problem of resistances, recidives and toxicity, done by the longer treatments, that give the, as said, ATRA syndrome and teratogenicity. In these cells we found that the combination among ATRA and MC1568 seems synergic, inducing a caspase independent cell death, even if in presence of caspases activation. The ZVAD inhibitor (pan-inhibitor for all caspases) failed to block the death induced by the MC1568 and by the combination among the two compounds. Analyzing the activation of the caspases it seemed that the pathway activated was mainly mediated by caspase 8. At the same time we found a strong release of cytochrome C, demonstrating the involvement of the mitochondria in the death induced by these two compounds. The use of a specific inhibitor, the NAC inhibitor, was able to reduce the death mediated by ATRA and MC1568, showing that the pathway was mainly regulated by the NAC dependent way. At this time, we are arrived to select the pathway regulated by this compound. Knowing that an HDAC inhibitor like MS275, specific inhibitor for class 1 HDACs, induce in the same system a caspase-dependent cell death, mainly regulated by TRAIL3, our observation would suggest that the class 2 HDAC inhibition is specifically regulating a pathway that is mainly caspase-independent. This observation could be usefull for treatment therapy, not only ammeliorating the treatment with retinoids, but overcoming possible resistances mediated by mutations and alteration in receptor expression in tumoral cells. Conclusions In my work I have evaluated the effect of a class 2 HDAC inhibitor in several systems, differentiative and cancerous, highlighting its effects in transcriptional regulation and cell death
Nell’uomo gli enzimi de acetilanti gli istoni appartengono ad una famiglia di 18 membri che sono raggruppati in 4 classi. La classe I (HDAC1-3,8), classe II (HDAC4-7,9,10 di cui HDAC4, 5,7,9 formano un subgruppo dovuta ad una comune organizzazione strutturale, mentre HDAC6 è un membro della classe 2), classe III, denominata come sirtuine (SIRT1-7) e classe IV (HDAC11). Le HDAC appartenenti alle classi I, II, IV sono comunemente dipendenti dallo zinco, mentre le HDAC appartenenti alla classe III sono enzimi dipendenti dal NAD +(1). SAHA, un pan inibitore delle HDAC, inibisce entrambi le classi I e II. Attualmente è in phase III clinical trials ed è stato recentemente approvato per il trattamento del linfoma cutaneo delle cellule T. MS275, invece, è un inibitore selettivo per la subclasse I, bloccando preferenzialmente HDAC1,2. Recentemente sono stati sintetizzati anche inibitori selettivi per la classe II, rendendo possibile lo studio delle varie funzioni delle differenti classi delle HDAC. Come è noto, mentre l’induzione di TRAIL sembra essere associata con l’inibizione di enzimi classe I in sistemi cancerosi, le HDAC di classe II sembrano essere coinvolte in altra funzioni cellulari, come la regolazione del differenziamento, principalmente quello cardiaco. Inibitori delle HDAC in sistemi differenziativi: le cellule C2C12, le cellule F9 e le cellule 3T3L1. Abbiamo testato un nuovo composto inibitore HDAC, specifico per la classe 2 in un modello leucemico, le cellule U937, e vari sistemi differenziativi, come le cellule C2C12 per il differenziamento cardiaco, le cellule F9 per il differenziamento endodermico e le cellule 3T3L1 per il differenziamento adipocitario. Abbiamo scoperto che nelle cellule C2C12 l’inibitore HDAC classe 2 stabilizzò l’interazione tra il fattore trascrizionale MEF2D ed HDAC4, pur bloccando l’azione catalitica delle HDAC classe II. MEF2D è il principale fattore trascrizionale resposabile del differenziamento cardiaco terminale e l’inibizione della sua attività trascrizionale conseguentemente bloccò il differenziamento muscolare. Negli altri due sistemi, similmente, noi abbiamo riscontrato l’inibizione del differenziamento ed abbiamo trovato che l’attività trascrizionale di RAR e PPARγ, essenziali per il differenziamento dei relativi sistemi differenziativi, fu bloccata sia in vitro nel primo caso che anche in vivo nel secondo. Nel caso del sistema differenziativo indotto da PPARγ, gli esperimenti furono fatti nelle 3T3L1. Il trattamento di queste cellule con Troglitazione indusse il differenziamento adipocitario, mentre la presenza dell’MC1568 lo bloccò completamente. Analizzando il livello di espressione di PPARγ per RT-PCR, abbiamo ritrovato che il suo livello era altamente decrementato dopo trattamento con MC1568. Abbiamo notato inoltre che il trattamento di un topo transgenico esprimente stabilmente il PPRE-luc, reporter luciferasi degli elementi responsivi a PPAR, bloccò completamente l’attività trascrizionale di PPARγ, mostrando in questo caso che il composto regolava sia l’attività trascrizionale del nuclear receptor sia il suo livello di espressione. In modelli cancerosi: le cellule MCF7 In sistemi cancerosi, così come le cellule MCF7 abbiamo riscontrato che lo specifico inibitore delle HDAC di classe II induceva la sumoilazione di HDAC4, che, come previamente mostrato (2) incrementa l’azione catalitica di HDAC4. La trasfezione di un mutante di HDAC4 specifico per il sito di sumoilazione nelle cellule F9 decrementò il potere repressorio su un noto target di RAR, CollagenIV. Abbiamo dimostrato che il trattamento con MC1568 regolò l’attività di due fattori trascrizionali, quali RAR alpha ed NF-KB, su tre geni target, IFR1, TNF e TRAIL. La sumoilazione di HDAC4 mediata da RANBP2 represse in modo transiente l’espressione di questi geni target, che furono up-regolati dopo la completa degradazione di HDAC4. Leucemia promielocitica acuta (APL), NB4 cells Le cellule NB4 è un sistema cellulare di leucemia promielocitica acuta (APL). Questa malattia è caratterizzata dalla presenza di una proteina di fusione, PMLRAR alpha, con un forte attività repressoria. I pazienti sono attualmente curati con la terapia differenziativa con acido retinoico (ATRA). Anche se è un trattamento molto efficiente, vi sono ancora casi di recidività, resistenze e tossicità al trattamento, dovuto principalmente ai trattamenti prolungati, dando luogo alla cosiddetta ATRA sindrome e teratogenicità. In queste cellule abbiamo scoperto il sinergismo tra ATRA e MC1568. La combinazione delle due droghe ha indotto una morte caspasi-indipendente, anche se in presenza di attivazione delle caspasi. L’inibitore ZVAD, infatti, fallì a bloccare la morte indotta dall’MC1568 e dalla combinazione tra i due composti. Analizzando l’attivazione delle caspasi, abbiamo riscontrato che il pathway maggiormente attivato è quello della caspasi 8. Allo stesso tempo abbiamo ritrovato un forte rilascio del citocromo C, dimostrando il coinvolgimento del mitocondrio nella morte indotta da questi due composti. L’uso di un inibitore specifico dei reattivi dell’ossigeno, N-acetyl-cisteina, ridusse significativamente la morte indotta, definendo il ruolo chiave dei ROS. Sapendo che un inibitore delle HDAC quale MS275, un inibitore specifico delle HDAC di classe 1, inducesse nello stesso sistema una morte caspasi dipendente, principalmente regolata da TRAIL3, la nostra osservazione suggerirebbe che l’inibizione specifica delle HDAC di classe II regola specificamente un pathway caspasi-indipendente, utile per migliorare il trattamento con retinoidi, ma soprattutto per curare quei pazienti con resistenze dovute a mutazioni o alterazione nella espressione del recettore in cellule tumorali. In Conclusione Nel mio lavoro ho studiato l’effetto di un inibitore specifico delle HDAC di classe II in svariati sistemi, differenziativi e cancerosi, concentrandomi sugli effetti nella regolazione trascrizionale e la morte cellulare
Lehmann, Annika [Verfasser]. "Rolle der Histondeacetylase (HDAC) in humanen soliden Tumoren / Annika Lehmann." Berlin : Medizinische Fakultät Charité - Universitätsmedizin Berlin, 2009. http://d-nb.info/1023704358/34.
Повний текст джерелаTuttle, Camilla Susannah Laura. "The expression of HAT and HDAC enzymes in asthma airways." Thesis, Queensland University of Technology, 2013. https://eprints.qut.edu.au/62873/1/Camilla_Tuttle_Thesis.pdf.
Повний текст джерелаRoy, Jean-Sébastien. "HDAC-independent transcriptional repression by RBPI is modulated by SUMO modification." Thesis, McGill University, 2003. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=80869.
Повний текст джерелаHesping, Eva M. "New inhibitors and tools to advance HDAC drug discovery for malaria." Thesis, Griffith University, 2021. http://hdl.handle.net/10072/403646.
Повний текст джерелаThesis (PhD Doctorate)
Doctor of Philosophy (PhD)
School of Environment and Sc
Science, Environment, Engineering and Technology
Full Text
pinazza, marica. "HDAC INHIBITORS TARGET TRANSCRIPTION FACTORS DEREGULATED IN T-ACUTE LYMPHOBLASTIC LEUKAEMIA." Doctoral thesis, Università degli studi di Padova, 2014. http://hdl.handle.net/11577/3423668.
Повний текст джерелаLe Istone Deacetilasi (HDACs) sono enzimi coinvolti nel rimodellamento della cromatina. Negli ultimi anni è emerso come l’inibizione delle HDACs potrebbe essere utilizzata come strategia per ripristinare l’alterata regolazione epigenetica che si riscontra nei tumori. Infatti, gli inibitori delle HDAC (HDACi) inducono apoptosi, arresto del ciclo cellulare e differenziamento delle cellule tumorali, ma i meccanismi molecolari alla base di questi fenomeni rimangono poco chiari. La leucemia linfoblastica acuta a cellule T (T-ALL) è un tumore pediatrico caratterizzato dall’espansione clonale di progenitori linfoidi. Nonostante la maggioranza dei pazienti pediatrici affetti da T-ALL siano curati in modo efficace utilizzando gli attuali protocolli terapeutici, circa un quarto dei pazienti manifesta resistenza alla terapia o presenta ricadute e dunque emerge la necessità di nuovi approcci terapeutici. In questo studio abbiamo analizzato gli effetti degli HDACi nei confronti di sette fattori di trascrizione implicati nella patogenesi della T-ALL (NOTCH1, NOTCH3, c-MYB, TAL1, TLX1, TLX3 and LMO2) utilizzando sia linee cellulari stabilizzate, sia modelli murini di T-ALL precedentemente sviluppati nel nostro laboratorio a partire da cellule di pazienti. In particolare, ci siamo concentrati su fattori trascrizionali che identificano specifici sottogruppi di T-ALL (TAL/LMO, TLX1 e TLX3) e abbiamo incluso nell’analisi due membri della famiglia dei recettori Notch (NOTCH1 and NOTCH3) e c-MYB in virtù del loro ruolo oncogenico in questa patologia. Le analisi in vitro hanno evidenziato diversi meccanismi di regolazione dei vari fattori da parte degli HDACi. TAL1 e c-MYB risultano regolati a livello trascrizionale, NOTCH1 e NOTCH3 presentano una regolazione post-traduzionale e, nel caso di TLX 1 e TLX3, è presente una regolazione diretta della loro capacità trascrizionale. Gli effetti a livello di proteina si legano all’induzione di apoptosi e all’inibizione della proliferazione sia nelle linee cellulari, sia nelle cellule derivate da paziente e risultano essere parzialmente dovute alla down-modulazione di NOTCH1 e NOTCH3. In seguito siamo andati ad indagare la risposta in vivo di un HDACi in xenografts di T-ALL appartenenti a specifici sottogruppi genetici. E’ interessante notare che il trattamento ha avuto il maggiore risultato nelle PD-TALL8 (TLX1) e nelle PD-TALL16 (TLX3) rispetto alle PD-TALL12 e le PD-TALL9 (entrambe TAL/LMO). Infatti, il trattamento con HDACi negli xenografts di tipo TLX determina una riduzione dell’infiltrazione da parte delle cellule leucemiche nella milza e nel midollo mentre gli effetti ottenuti negli xenografts TAL/LMO risultano modesti o addirittura nulli. In conclusione, i dati ottenuti identificano i pazienti di T-ALL appartenenti ai sottogruppi TLX1 e TLX3 come potenziali candidati per il trattamento a scopo terapeutico con HDACi.
Fritah, Sabrina. "Implications des histones deacetylases de I et II dans la réponse au stress." Université Joseph Fourier (Grenoble), 2008. http://www.theses.fr/2008GRE10270.
Повний текст джерелаLn response to environmental stress (heat shock, hypoxia, heavy metals exposure), cells have developed rapid and transitory mechanisms to protect themselves from the stress-induced damages. This stress response is characterized by the activation of HSF1 (Heat Shock Factor1), a key factor involved in the induction of the HSP (Heat Shock Proteins) encoded genes. Ln contrast toheat shock genes induction, most of the genome is repressed du ring stress. If the mechanisms involved in the activation of HSP genes have been investigated in details, less is known about the global repression of the genome. We started to investigate the epigenetic mechanisms that underline this genome repression and identify the molecular basis of this phenomenon. By molecular and in situ approaches, we showed that HDACs (Histone Deacetylases) are new regulators of stress response. Heat shock induces major epigenetic changes, specially a global deacetylation of core histones. We showed that class 1 HDAC, HDACl and HDAC2 mediates the heat-induced deacetylation. This event is regulated by HSF1, probably through its interaction with HDACl and HDAC2. Ln the cytoplasm, HDACS are also able to regulate stress response. Indeed, upon proteotoxic stress for example, proteasome inhibition, we showed that HDAC6 play a critical role in initiating the stress response. It mediates the dissociation of HSFl from its repressor complex and HDAC6 has an impact in HSP induction in response to stress. Ln conclusion, we identify HDACs as new important factors of stress response. Thanks to this work, we have linked two classes of proteins that are targeted by anti-cancer therapy: HSPs and HDACs
Leteve, Mathieu. "EPIADDICT - Synthèses de nouveaux inhibiteurs des histones désacétylases et leur intérêt dans un modèle préclinique d’addiction à l’alcool." Thesis, Reims, 2016. http://www.theses.fr/2016REIMS026/document.
Повний текст джерелаThe imbalance HAT/HDAC would influence the development of cancers and alcohol or cocaine addiction. HDAC inhibition allows increase of both acetylation rate and gene expression. Today, there are many structurally diverse potent, but non-specific HDAC inhibitors displaying important side-effects. HDAC inhibitors such as sodium butyrate or MS-275 have been shown to alter the alcohol dependence in the rat. MS-275 inhibits mainly class I of HDAC and in line with these observations we are interested in more selective class I inhibitors such as Largazole thiol and RedFK228. Our purpose is to synthesize new cyclodepsipeptides analogues in order to obtain selective class I inhibitor. HDAC class I is a Zn-dependent enzyme and our target molecules have sulfonylhydrazide function as efficient Zinc binding group (ZBG). Additional pharmacomodulations concern the incorporation of different heterocycles (oxazole, thiazole, pyridine) and varying linker lengths (n = 2, 3). Inhibitions of these compounds have been tested on HDAC1, HDAC3 and HDAC6. A compound has specificity for HDAC3 and another has specificity for HDAC1. Tests on rats "binger" suggest that HDAC1 is involved in this model of consumption and not HDAC3
Wegener, Dennis. "Entwicklung eines HTS-geeigneten Enzymtests für Histondeacetylasen zur Entwicklung von HDAC-Inhibitoren." [S.l.] : [s.n.], 2003. http://deposit.ddb.de/cgi-bin/dokserv?idn=972620621.
Повний текст джерелаDi, Fruscia Paolo. "The design, synthesis and biological evaluation of novel small-molecule HDAC inhibitors." Thesis, Imperial College London, 2012. http://hdl.handle.net/10044/1/39126.
Повний текст джерелаHorton, Kyle L. "Synthesis and characterization of biodegradable poly(vinyl esters) with HDAC inhibitory activity." Thesis, Wayne State University, 2013. http://pqdtopen.proquest.com/#viewpdf?dispub=1537532.
Повний текст джерелаHDAC inhibitors are known to have anti-inflammatory properties. HDAC inhibitors are used in combination with Oct4 to generate induced pluripotent stem cells. I hypothesized that polyesters based on simple aliphatic HDAC inhibitors like valproic acid (VPA) and phenylbutyric acid (PBA) can serve as alternatives to existing polyester biomaterials with improved anti-inflammatory properties and as scaffolds for generation of iPSCs when used in combination with layer-by-layer thin films delivering reprogramming transcription factors. Vinyl ester of phenylbutyric acid (VEPA) and vinyl ester of valproic acid (VEVA) were synthesized from their carboxylic acid precursors using an iridium complex catalyst at yields as high as 97% and 73%, respectively. Amorphous poly(VEPA) and poly(VEVA) polymers were prepared by free radical solution polymerization and characterized for molecular weight and glass transition temperature. Poly(VEPA) and poly(VEVA) microparticles of 20-40 um diameter were prepared by an emulsion-solvent evaporation method and examined under scanning electron microscopy (SEM). Their hydrolytic degradation was studied by dry weight loss and HDAC inhibitor release via high performance liquid chromatography (HPLC) in the presence of varied pH and lipase-containing buffers. No significant degradation occurred within 5 days, and an MTT assay conducted on HeLa cells in the presence of these microparticles confirmed an absence of cytotoxicity. Poly(VEPA) and poly(VEVA) microparticles were not found to be a suitable biomaterial for hypothesized applications in light of their poor degradation characteristics in vitro.
Laine, Vivien. "Polarimetry of the polarized hydrogen deuteride HDice target under an electron beam." Phd thesis, Université Blaise Pascal - Clermont-Ferrand II, 2013. http://tel.archives-ouvertes.fr/tel-00975926.
Повний текст джерелаHuang, Rui. "Roles of HDACs in chromatin remodelling and response to chemotherapy in cancer." Thesis, University of Edinburgh, 2014. http://hdl.handle.net/1842/9626.
Повний текст джерелаKim, Wanhui. "Rôle de l'acétylation des histones dans le contrôle de l'expression du génome d'Arabidopsis thaliana." Paris 11, 2008. http://www.theses.fr/2008PA112156.
Повний текст джерелаHistone acetylation appears as a central switch for interconversion between permissive and repressive state of chromatin domains. Homeostasis of histone acetylation is made sure by histones acetyltransferases (HAT) and histones desacetylases (HDAC). But their role on chromatin and transcriptional/posttranscriptional regulation was not clear. The objective of my work was to study the role of histone acetylation in the control of gene expression in Arabidopsis thaliana. For this reason, HAT and HDAC mutants had been identified and characterized. First of all, we show that AtGCN5 interfere, in the pathway of miRNA, on transcriptional and posttranscriptional regulation of gene. It indicates that histone acetylation/desacetylation is an epigenetic mechanism involved in the regulation of miRNA production. Characterization of the mutants reveled that AtHDA9 mutation induces a phenotype of early flowering in short days. This characteristics is associated with overexpression of activator genes in the pathway of flowering. AtHDA9 and AtSRT2 mutation affect also DNA méthylation of pericentromeric sequence repeat 180 bp and retroelement AtSN1. Our results reveal the different role of individual HAT and HDAC in the control of genome expression of Arabidopsis
Traore, Mohamed Dit Mady. "Synthèse et études de modélisation moléculaire dans l'optimisation de la sélectivité de nouveaux agents antiparasitaires inspirés de produits naturels." Thesis, Université Grenoble Alpes (ComUE), 2016. http://www.theses.fr/2016GREAV027/document.
Повний текст джерелаAculeatins and FR235222 are two families of natural products that are highly effective against apicomplexan parasites, responsible for malaria and toxoplasmosis. In the first part of this work, we developed a new reaction involving a “one pot” phenolic oxidation cascade sequence using a hypervalent iodine reagent in catalytic condition. This flexible synthetic strategy will increase accessibility to new aculeatin derivatives to achieve bioactive compounds. In the second part, we were interested in FR235222, an HDACi (histone deacetylase inhibitor) which targets the class I human HDAC and parasite T. gondii HDAC3 responsible for toxoplasmosis. HDACs are proteins that play an important role in the control of epigenetic mechanisms. In this study, a FR235222 fluorescent derivative was synthesized to confirm the FR235222 target in human cells through cellular localization studies. The synthesis and assessment of the activity of new HDACi analogues, combined with molecular modelisation studies, allowed to demonstrate for the first time that the keto-hydroxyl zinc binding group and the flexibility of the linker would be responsible for this selectivity on human class I HDACs. Finally, with these results in hand and the identification of structural differences between human and parasitic HDAC3, prediction studies (docking) have revealed structural determinants to design inhibitors selective for apicomplexan parasites HDACi
Sena, Elena. "The Transcription Factor Barhl2 Inhibits Wnt Canonical Signaling during Xenopus Embryogenesis." Thesis, Université Paris-Saclay (ComUE), 2018. http://www.theses.fr/2018SACLS090/document.
Повний текст джерелаEmbryonic development is a highly controlled process where different signaling pathways participate into the elaboration of an organism. One of the main signaling pathways is the Wnt canonical pathway. The long-lasting search to understand Wnt/β-catenin transduction cascade revealed that the net transcriptional read out of Wnt/β-catenin signaling is highly dependent on the cellular context. In X. laevis embryos Wnt/β-catenin signaling is the informative signal for the Spemann Organizer induction. However little is known on what limits Wnt activity in this territory and consequently the size of the Spemann Organizer. The results presented in this manuscript provide evidence that the evolutionarily conserved transcription factor Barhl2 limits the development of the Spemann organizer. In this territory Barhl2 inhibits Wnt activity via its interaction with the co-repressor Groucho and the transcription factor Tcf. It participates to the recruitment of the chromatin remodeling enzyme, Hdac1 that represses the expression of Spemann organizer genes. Using a Xenopus tropicalis Tcf reporter line we demonstrate that Barhl2 inhibitory effect on Groucho-Tcf activities is maintained during embryogenesis and plays a role in the confinement of neural progenitors in the brain. Together, our results provide a new and important mechanism for the control of Wnt transcriptional activity
Pehrsson, Åsa. "Välfärd : en analys av BNP och HDI som välfärdsmått." Thesis, Linköping University, Department of Management and Economics, 2001. http://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-968.
Повний текст джерелаDet finns en kedja till en bra välfärd. Alla individer har behov och önskningar. Dessa ska tillgodoses med de resurser som landet får genom sin årliga produktion av varor och tjänster, BNP. Hur resurserna ska fördelas är en politisk fråga. Det är svårt att mäta välfärd. Några problem kan vara:"Reducering av verklighetens pluralism och mångfald"; Individernas olika preferenser Olika välfärdsmått är bruttonationalprodukten (BNP), Human Development Index (HDI) och Physical Quality of Life Index (PQLI). Där BNP är rent baserat på produktion medan HDI och PQLI är sammansatta index med olika indikatorer. Min analys går ut på att jämföra 3 i-länder samt 3 u-länder för att urskilja något samband mellan dels tillväxt och HDI. Jag söker också ett svar på hur storleken på de offentliga utgifter påverkar tillväxten samt HDI. Tillväxten har ökat i så väl i-länderna Sverige, USA och Japan som u-länderna Haiti, Bangladesh och Nigeria. HDI har dock minskat i i-länderna men ökat i u- länderna. Min analys visar att Japan är det enda land av de tre observerade i- länderna som har ökat sin offentliga konsumtion. Sverige och USA har minskat sin offentliga konsumtion mellan åren 1987 och 1997.
Palma, Camila de Souza. "Avaliação de alterações proteômicas em diferentes modelos de indução da transição epitelial-mesenquimal (EMT) em células de adenocarcinoma de mama." Universidade de São Paulo, 2018. http://www.teses.usp.br/teses/disponiveis/17/17131/tde-01022019-102412/.
Повний текст джерелаTumor development is a process comprising several steps and consists in the progressive development of normal cells into a neoplastic state through various biochemical and phenotypic changes. Among the major marks of cancer are the capacity for tissue invasion and metastasis. Metastasis accounts for approximately 90% of cancer deaths. Thus, the most effective methods for improving cancer-related morbidity and mortality rates are early detection, prevention and treatment of metastasis. The EMT process, which occurs naturally during embryogenesis and tissue repair, is also involved in cancer progression and metastasis. EMT induces complex cellular and microenvironmental changes that result in the acquisition of a mesenchymal phenotype by epithelial cells, together with an increase in migratory and invasive cellular capacities. EMT can be induced by various extracellular factors, such as TGF?, EGF, HGF and PDGF. In addition, overexpression of some transcription factors such as SNAIL, SLUG, ZEB1 and TWIST1 is also capable of inducing EMT in vitro. In order to increase the knowledge of the mechanisms involved in the EMT process, we performed proteomic analysis in different models of EMT induction in the MCF7 breast adenocarcinoma cell line, which were the overexpression of SNAIL, treatment with the histone deacetylase inhibitor SAHA and treatment with the growth factor EGF. The detailed proteomic analysis by LC-MS/MS of the subcellular fractions of nucleus, cytoplasm and membrane of the overexpressing SNAIL cells generated a list of regulated proteins related to the EMT process and that were evaluated in the other models of induction. Among these, the HDAC1 protein, which had its levels decreased by SNAIL overexpression. Treatment of the MCF7 cell line with the histone deacetylase inhibitor SAHA showed a positive correlation with the increase of SNAIL levels, suggesting a cross-talk between both proteins. In addition, SAHA treatment induced cellular and protein alterations that also suggest the induction of the EMT process in MCF7 cells. Finally, the treatment with the growth factor EGF was also able to induce the EMT in MCF7 cells and showed involvement in the regulation of the cell cycle, changes in proteins in common with the other treatments and differential regulation of proteins among thesubcompartiments, indicating similarities between the processes and potential mechanisms of subcellular translocation. In conclusion, this study revealed target proteins related to EMT, opening possibilities to try to alter processes related to tumor progression and metastatic process.
Bridgeman, Stephanie Claire. "Epigenetics, cholesterol lowering and diabetes: a comparative study of statins and HDAC inhibitors." Thesis, Curtin University, 2022. http://hdl.handle.net/20.500.11937/88742.
Повний текст джерелаAnderson, Letícia. "Regulação epigenética da expressão gênica de Schistosoma mansoni induzida por inibidor de histona deacetilase." Universidade de São Paulo, 2016. http://www.teses.usp.br/teses/disponiveis/46/46131/tde-20092016-094835/.
Повний текст джерелаSchistosomiasis is a serious public health problem, with high mortality and morbidity in endemic countries, caused by trematode worms of the genus Schistosoma. Praziquantel is the only available drug for treatment of the disease; it is used extensively to treat populations in endemic areas, but does not prevent reinfection and is effective only in adult worms. Drugs studied in cancer as histone deacetylase inhibitors (iHDACs) modify the epigenetic status of the cell, triggering cell death, and it has been shown in Schistosoma mansoni that inhibition of HDACs increase histone acetylation, alter the phenotype of miracidia and cause death in schistosomules and adult worms. The present study investigated the effect of iHDAC Trichostatin A (TSA) on the regulation of gene transcription in schistosomules, detecting by means of microarray assays hundreds of differentially expressed genes related to DNA replication, metabolism and histone remodeling complexes. Inhibition of HDAC in adult worms led to an increase in histone acetylation marks H3K9ac, and H3K14ac H4K5ac related to transcriptional induction. With chromatin immunoprecipitation followed PCR (ChIP-qPCR) we detected an increased deposition of H3K9ac and H3K14ac at the promoter region of genes with increased or decreased expression, but the repressive mark H3K27me3 was not changed at all analyzed gene promoter regions. Additional analysis indicated a set of differentially expressed genes that encode histone reader proteins that are part of histone modifier complexes such as EED, which is able to identify the repression mark H3K27me3 and to regulate EZH2 activity, pointing to a new therapeutic target. The synergistic effect between iHDAC and one iEZH2 has been tested and found to cause an increase in schistosomules mortality. The SmEZH2 structure was modeled by homology and used for computational analyses, which suggested a high affinity binding of SmEZH2 with iEZH2, opening the opportunity for development of new specific drugs for treatment of schistosomiasis.
Al-Hamashi, Ayad Abed Ali Chiad A. "Design, Synthesis, and Biological Evaluation of Novel Histone Deacetylase Inhibitors as Anti-Cancer Agents." University of Toledo / OhioLINK, 2018. http://rave.ohiolink.edu/etdc/view?acc_num=toledo1525945712448479.
Повний текст джерелаServatius, Phil [Verfasser], and Uli [Akademischer Betreuer] Kazmaier. "Total synthesis of natural HDAC inhibitors and derivatives thereof / Phil Servatius ; Betreuer: Uli Kazmaier." Saarbrücken : Saarländische Universitäts- und Landesbibliothek, 2018. http://d-nb.info/1172288003/34.
Повний текст джерелаArndt, David L. "Role of HDAC inhibition and environmental condition in altering phases of amphetamine self-administration." Diss., Kansas State University, 2016. http://hdl.handle.net/2097/32694.
Повний текст джерелаPsychological Sciences
Mary E. Cain
Gene-environment interactions play a significant role in drug abuse and addiction. Epigenetics (the study of how environmental stimuli alter gene expression) has gained attention in recent years as a significant contributor to many behavioral phenotypes of drug addiction. The current study sought to determine if differential rearing conditions can alter a specific epigenetic mechanism, histone deacetylase (HDAC), and how HDAC inhibition can affect drug-taking and drug-seeking behaviors differently among enriched, isolated, or standard-housed rats. Ninety male Sprague-Dawley rats were reared for 30 days in enriched (EC), isolated (IC), or standard (SC) conditions prior to amphetamine (0.03, 0.05, 0.1 mg/kg/infusion, i.v.) self-administration, extinction, or reinstatement sessions. Trichostatin A (TsA; 0.3 mg/kg, i.v.), an HDAC inhibitor, was injected 30 min prior to drug-taking or drug-seeking sessions. Results indicated that EC rats self-administered less amphetamine (0.03 mg/kg/infusion) than IC rats. No significant effects of TsA administration were found on general self-administration for any of the three amphetamine doses. While enrichment facilitated the extinction of active lever pressing, there was also a mild facilitation of extinction in IC-TsA rats compared to IC-vehicle counterparts. Lastly, TsA administration decreased cue-, but not drug-induced reinstatement, with IC-TsA rats exhibiting significantly attenuated cue-induced reinstatement compared to IC-vehicle rats. These findings suggest that differential rearing can alter HDAC mechanisms that can change drug-seeking behaviors, particularly in rats reared in isolated conditions. While TsA-induced HDAC inhibition may be less protective against general amphetamine self-administration, it may decrease drug-seeking tendencies during relapse that are induced by the reintroduction of contextual environmental cues heavily associated with drug reward.
Perikala, V. "Understanding the relevance of epigenetic reprogramming for resistance to HDAC inhibitors in cancer cells." Thesis, University of Liverpool, 2016. http://livrepository.liverpool.ac.uk/3004805/.
Повний текст джерелаServatius, Phil Verfasser], and Uli [Akademischer Betreuer] [Kazmaier. "Total synthesis of natural HDAC inhibitors and derivatives thereof / Phil Servatius ; Betreuer: Uli Kazmaier." Saarbrücken : Saarländische Universitäts- und Landesbibliothek, 2018. http://nbn-resolving.de/urn:nbn:de:bsz:291-scidok-ds-275430.
Повний текст джерелаMatsubara, Hiroshi. "Involvement of ERK activation in human osteosarcoma cell resistance to the HDAC inhibitor FK228." Kyoto University, 2009. http://hdl.handle.net/2433/126457.
Повний текст джерелаStamatakos, Serena <1993>. "Effects of 3,4-methylenedioxymethamphetamine (MDMA) on BDNF pathway, HDAC epigenetic enzymes and neurofilament proteins." Doctoral thesis, Alma Mater Studiorum - Università di Bologna, 2022. http://amsdottorato.unibo.it/10104/1/PhD_Thesis_StamatakosSerena.pdf.
Повний текст джерелаSmith, Kyle Edward. "Thermo-mechanical behavior and reliability of High Density Interconnect (HDI) vias." Thesis, Georgia Institute of Technology, 1997. http://hdl.handle.net/1853/17981.
Повний текст джерелаAndrade, Pamela Viani de. "Inibidor de histona deacetilase (HDACi) como possível radiosensibilizante em linhagens celulares de glioblastoma pediátrico." Universidade de São Paulo, 2015. http://www.teses.usp.br/teses/disponiveis/17/17144/tde-07012016-094449/.
Повний текст джерелаGlioblastoma (GBM) is considered one of the most aggressive tumors to affect the central nervous system (CNS). Even employing modern treatment protocols the prognosis remains very poor, with children affected by GBM presenting a median survival rate of 12 to 15 months. Epigenetic mechanisms may interfere with the process of tumorigenesis, and DNA acetylation can modulate the expression of genes that contribute in cell cycle control and participate to the development and progression of cancer. Clinical studies demonstrate that histone deacetylase inhibitors (HDACs), alone or in combination with other antineoplastic agents, are clinically active and well tolerated in the treatment of a wide variety of tumors. These inhibitors may sensitize the cellular response to ionizing radiation, enabling the reduction in standard doses of radiation, ultimately minimizing both short and long-term side effects. Ionizing radiation induces DNA damage and it is generally accepted that the double-stranded breaks (DSBs) is the most severe type of injury related to cell survival and preservation of genomic integrity. In the present study, we evaluated the potential radiosensitizer effect of PCI-24781, a novel potent pan-HDAC inhibitor in the pediatric GBM cell lines SF188 and KNS42. We compared the cell proliferation rates, apoptosis of clonogenicity of KNS42 and SF188, with or without treatment with PCI-24781. Moreover, clonogenicity rates were compared between cell lines that were irradiated with or without prior treatment with PCI-24781 Additionally, we evaluated the effects of PCI-24781 in the expression of some of the major proteins responsible for the repair of double-stranded breaks caused by the irradiation. For the cell proliferation assays, the times of 24, 48, 72 and 96 hours were used, for apoptosis, the time of 48h and clonogenic capacity without irradiation, the time of 48h, and different doses of PCI-24781 (0,25 - 16 M). The inhibitor significantly blocked cell proliferation (p<0,05), inducing cell death by apoptosis (p<0,05) and reducing the colony forming ability (p<0,001) of both lineages. In the assays to evaluate the radiosensitivity , the IC30 doses of the clonogenic assays were used for each cell-line after different doses of irradiation. Both lineages showed a significant decrease (p<0,001) in colony formation at all doses of irradiation. The most resistant cell-line to the drug, SF188, was 13 chosen to study the double-strand breaks repair caused by irradiation. The Rad51 protein levels, critical for homologous recombination (HR), and the DNA-PKcs proteins Ku70 and Ku86, important for DNA repair through non-homologous end joining (NHEJ) showed significant decrease in expression when cell-line was treated with PCI-24781 prior to radiotherapy. These data demonstrates that the histone deacetylase inhibitor PCI-24781 plays an important role as a radiosensitizer agent, compromising the repair of double-strand breaks in pediatric GBM cells following irradiation.
SONCINI, MATIAS CRISTOBAL. "Epigenetic therapies for acute myeloid leukemias : pre-clinical validation and study of molecular mechanisms." Doctoral thesis, Università degli Studi di Milano, 2008. http://hdl.handle.net/2434/56628.
Повний текст джерелаVega, García Nerea. "Estudi del perfil d’expressió de les histones deacetilasa (HDAC) en pacients pediàtrics amb leucèmia aguda." Doctoral thesis, Universitat de Barcelona, 2018. http://hdl.handle.net/10803/666190.
Повний текст джерелаHistone deacetylase inhibitors (HDACi) emerged as promising drugs in leukaemia, but their toxicity due to lack of specificity limited their use. Therefore, there is a need to elucidate the role of HDACs in specific settings. The study of HDAC expression in childhood leukaemia could help to choose more specific HDACi for selected candidates in a personalized approach. We analysed HDAC1-11, SIRT1, SIRT7, MEF2C and MEF2D mRNA expression in 211 paediatric patients diagnosed with acute leukaemia. We found a global overexpression of HDACs, while specific HDACs correlated with clinical and biological features, and some even predicted outcome. Thus, some HDAC and MEF2C profiles probably reflected the lineage and the maturation of the blasts and some profiles pointed out specific oncogenic pathways active in the leukaemic cells. Specifically, we identified a distinctive signature for patients with MLL rearrangement, with high HDAC9 and MEF2D expression, regardless of age, MLL-partner and lineage. Moreover, we observed an adverse prognostic value of overexpression of HDAC9, regardless of MLL rearrangement. Our results provide useful knowledge on the complex picture of HDACs expression in childhood leukaemia and support the directed use of specific HDACi to selected paediatric patients with acute leukaemia.
Chen, Chang-Shi. "Beyond induction of histone acetylation the multi-facets of the antineoplastic effect of HDAC inhibitors /." Columbus, Ohio : Ohio State University, 2006. http://rave.ohiolink.edu/etdc/view?acc%5Fnum=osu1164649581.
Повний текст джерелаNew, Maria. "Role of HR23B, HDAC6 and Myd88 and their interplay in response to HDAC inhibitor treatment." Thesis, University of Oxford, 2014. http://ora.ox.ac.uk/objects/uuid:096a4afc-98fa-41d5-b163-9287984cb1fa.
Повний текст джерела