LIVIVO - The Search Portal for Life Sciences

zur deutschen Oberfläche wechseln
Advanced search

Search results

Result 1 - 10 of total 229

Search options

  1. Article ; Online: Re: Abiraterone and Olaparib for Metastatic Castration-resistant Prostate Cancer.

    Giesen, Alexander / Devlies, Wout / Claessens, Frank / Joniau, Steven

    European urology

    2023  Volume 85, Issue 4, Page(s) 396

    MeSH term(s) Male ; Humans ; Prostatic Neoplasms, Castration-Resistant/drug therapy ; Prostatic Neoplasms, Castration-Resistant/pathology ; Androstenes/therapeutic use ; Abiraterone Acetate/therapeutic use ; Antineoplastic Combined Chemotherapy Protocols ; Prednisone/therapeutic use ; Phthalazines ; Piperazines
    Chemical Substances abiraterone (G819A456D0) ; olaparib (WOH1JD9AR8) ; Androstenes ; Abiraterone Acetate (EM5OCB9YJ6) ; Prednisone (VB0R961HZT) ; Phthalazines ; Piperazines
    Language English
    Publishing date 2023-11-27
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 193790-x
    ISSN 1873-7560 ; 1421-993X ; 0302-2838
    ISSN (online) 1873-7560 ; 1421-993X
    ISSN 0302-2838
    DOI 10.1016/j.eururo.2023.11.014
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    In stock of ZB MED Cologne/Königswinter

    Zs.A 1247: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (1.OG)
    ab Jg. 2022: Lesesaal (EG)
    Zs.MO 294: Show issues

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

  2. Article ; Online: Tracking prostate cancer development at the single-cell level.

    Devlies, Wout / Claessens, Frank

    Nature reviews. Urology

    2021  Volume 17, Issue 10, Page(s) 545–546

    MeSH term(s) Humans ; Male ; Prostatic Neoplasms/diagnosis ; Radiotherapy, Intensity-Modulated
    Language English
    Publishing date 2021-04-09
    Publishing country England
    Document type Journal Article ; Comment
    ZDB-ID 2493737-X
    ISSN 1759-4820 ; 1759-4812
    ISSN (online) 1759-4820
    ISSN 1759-4812
    DOI 10.1038/s41585-020-0358-0
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    In stock of ZB MED Cologne/Königswinter

    Zs.A 6030: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
    ab Jg. 2022: Lesesaal (EG)

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

  3. Article ; Online: AR variants: lost in translation to clinical practice?

    Handle, Florian / Claessens, Frank

    Nature reviews. Urology

    2019  Volume 16, Issue 8, Page(s) 451–452

    MeSH term(s) Drug Resistance, Neoplasm ; Humans ; Male ; Prostatic Neoplasms/chemistry ; Prostatic Neoplasms/drug therapy ; Receptors, Androgen/analysis ; Receptors, Androgen/physiology
    Chemical Substances Receptors, Androgen
    Language English
    Publishing date 2019-06-10
    Publishing country England
    Document type News
    ZDB-ID 2493737-X
    ISSN 1759-4820 ; 1759-4812
    ISSN (online) 1759-4820
    ISSN 1759-4812
    DOI 10.1038/s41585-019-0204-4
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    In stock of ZB MED Cologne/Königswinter

    Zs.A 6030: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
    ab Jg. 2022: Lesesaal (EG)

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

  4. Article ; Online: Structural mechanism underlying variations in DNA binding by the androgen receptor.

    Lee, Xiao Yin / Van Eynde, Wout / Helsen, Christine / Willems, Hanne / Peperstraete, Kaat / De Block, Sofie / Voet, Arnout / Claessens, Frank

    The Journal of steroid biochemistry and molecular biology

    2024  Volume 241, Page(s) 106499

    Abstract: The androgen receptor (AR) is a steroid activated transcription factor which recognizes DNA motifs resembling inverted repeats of a conserved 5'-AGAACA-3'-like hexanucleotides separated by a three-nucleotide spacer from a similar, but less conserved ... ...

    Abstract The androgen receptor (AR) is a steroid activated transcription factor which recognizes DNA motifs resembling inverted repeats of a conserved 5'-AGAACA-3'-like hexanucleotides separated by a three-nucleotide spacer from a similar, but less conserved hexanucleotide. Here, we report the structures of the human AR DNA binding domain (DBD) bound to two natural AREs (C3 and MTV) in head-to-head dimer conformations, diffracting at 2.05 Å and 2.25 Å, respectively. These structures help to explain the impact of androgen insensitivity mutations on the structure integrity, DNA binding and DBD dimerization. The binding affinity of the AR DBD to different DNA motifs were measured by the BioLayer Interferometry (BLI) and further validated by Molecular Dynamics (MD) simulations. This shows that the high binding affinity of the first DBD to the upstream 5'-AGAACA-3' motif induces the cooperative binding of the second DBD to the second hexanucleotide. Our data indicate identical interaction of the DBDs to the upstream hexanucleotides, while forming an induced closer contact of the second DBD on the non-canonical hexanucleotides. The variation in binding between the DBD monomers are the result of differences in DNA occupancy, protein-protein interactions, DNA binding affinity, and DNA binding energy profiles. We propose this has functional consequences.
    Language English
    Publishing date 2024-04-10
    Publishing country England
    Document type Journal Article
    ZDB-ID 1049188-0
    ISSN 1879-1220 ; 0960-0760
    ISSN (online) 1879-1220
    ISSN 0960-0760
    DOI 10.1016/j.jsbmb.2024.106499
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    In stock of ZB MED Cologne/Königswinter

    Zs.A 708: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (1.OG)
    ab Jg. 2022: Lesesaal (EG)

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

  5. Article ; Online: Discovery of a novel androgen receptor antagonist, MEL-6, with stereoselective activity and optimization of its metabolic stability.

    Helsen, Christine / Karypidou, Konstantina / Thomas, Joice / De Leger, Wout / Nguyen, Tien / Joniau, Steven / Voet, Arnout / Dehaen, Wim / Claessens, Frank

    The Journal of steroid biochemistry and molecular biology

    2024  Volume 239, Page(s) 106476

    Abstract: A new chemical scaffold with antagonistic activity towards the androgen receptor (AR) was identified. The parent compound, (3-Methoxy-N-[1-methyl-2-(4-phenyl-1-piperazinyl)-2-(2-thienyl)ethyl]benzamide) referred to as MEL-6, binds in the ligand binding ... ...

    Abstract A new chemical scaffold with antagonistic activity towards the androgen receptor (AR) was identified. The parent compound, (3-Methoxy-N-[1-methyl-2-(4-phenyl-1-piperazinyl)-2-(2-thienyl)ethyl]benzamide) referred to as MEL-6, binds in the ligand binding pocket of AR and induces an antagonistic conformation of the ligand binding domain, even in presence of the antagonist-to-agonist switch mutations W741C, T877A and F876L-T877A. MEL-6 has antiproliferative effects on several AR positive prostate cancer cell lines. We further identified AR as the specific target of MEL-6 since it demonstrates little effect on other steroid receptors. In LNCaP cells it also inhibits the androgen-regulated transcriptome. These findings identify MEL-6 as a promising candidate for treatment of patients with prostate tumors that have become resistant to current clinically used AR antagonists. Analytical studies on the chemical composition of MEL-6 identified the presence of four isomers (two enantiomeric pairs), among which one isomer is responsible for the antiandrogenic activity. We therefore developed a synthetic route towards the selective preparation of the active enantiomeric pair. Various MEL-6-like analogues had improved metabolic stability while maintaining antiandrogenic activity. Metabolite identification of MEL-6 derivatives pinpointed N-dealkylation of the piperazine as the main mode for inactivation by liver enzymes. For further structural optimization, MEL-6 derivatives were purchased or synthesized having alterations on the N-phenyl group of the piperazine, the benzoyl group and additionally substituting the thiophen-2-yl ring of MEL-6 to a phenyl ring. This optimization process resulted in compound 12b with sustained AR inhibition and a 4-fold increased half-life due to the 1-(5-chloro-2-methylphenyl)-piperazine substitution, thienyl-to-phenyl substitution and chloro in para-position of the benzoyl group.
    MeSH term(s) Male ; Humans ; Androgen Receptor Antagonists/pharmacology ; Androgen Receptor Antagonists/chemistry ; Ligands ; Receptors, Androgen/metabolism ; Prostatic Neoplasms/metabolism ; Androgens ; Piperazines/pharmacology ; Cell Line, Tumor ; Androgen Antagonists/pharmacology
    Chemical Substances Androgen Receptor Antagonists ; Ligands ; Receptors, Androgen ; Androgens ; Piperazines ; Androgen Antagonists
    Language English
    Publishing date 2024-02-03
    Publishing country England
    Document type Journal Article
    ZDB-ID 1049188-0
    ISSN 1879-1220 ; 0960-0760
    ISSN (online) 1879-1220
    ISSN 0960-0760
    DOI 10.1016/j.jsbmb.2024.106476
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    In stock of ZB MED Cologne/Königswinter

    Zs.A 708: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (1.OG)
    ab Jg. 2022: Lesesaal (EG)

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

  6. Article ; Online: The Pixel Variation Score: An Echocardiographic Index to Assess Temporal Variation of Mitral Regurgitant Flow.

    Verbeke, Jonas / Kamoen, Victor / De Buyzere, Marc / Claessens, Tom / Timmermans, Frank

    Journal of the American Society of Echocardiography : official publication of the American Society of Echocardiography

    2023  Volume 37, Issue 3, Page(s) 316–324

    Abstract: Background: In mitral regurgitation (MR), temporal variation of MR flow has been considered an important reason for inaccurate MR grading. Current echocardiographic methods for assessing temporal MR flow variation are complex, and their clinical ... ...

    Abstract Background: In mitral regurgitation (MR), temporal variation of MR flow has been considered an important reason for inaccurate MR grading. Current echocardiographic methods for assessing temporal MR flow variation are complex, and their clinical relevance has not been investigated. In this study, we investigated whether assessing MR flow variation using a dimensionless index with echocardiography is feasible, clinically meaningful, and related to patient outcomes.
    Methods: Consecutive patients with mitral valve prolapse (MVP, n = 244) and functional MR (FMR, n = 396) underwent comprehensive echocardiography. Mitral regurgitation severity was assessed using an integrated approach advocated by current guidelines. The MR continuous-wave Doppler envelope was divided into 3 segments of equal duration. Each segment's pixel intensity was assessed to calculate the pixel variation score (PVS).
    Results: The PVS was lower in FMR patients than in MVP patients. Lower PVS was associated with worse MR, larger left atrial and left ventricular dimensions, lower ejection fraction, and higher pulmonary artery pressures. In MVP, PVS was significantly associated with postoperative left ventricular reverse remodeling and was able to reclassify most patients in whom single-frame measures overestimated MR severity. Finally, PVS had incremental prognostic value on top of clinical and echocardiographic predictors of outcome.
    Conclusions: Temporal variation in MR flow can reliably be assessed with echocardiography through analysis of the continuous-wave Doppler signal. A high PVS value may alert the echocardiographer to defer from single-frame MR grading and also suggests that the MR is probably not severe.
    MeSH term(s) Humans ; Mitral Valve Insufficiency/diagnostic imaging ; Mitral Valve Insufficiency/complications ; Mitral Valve Prolapse ; Echocardiography ; Heart Atria/diagnostic imaging ; Atrial Appendage ; Severity of Illness Index
    Language English
    Publishing date 2023-10-30
    Publishing country United States
    Document type Journal Article
    ZDB-ID 1035622-8
    ISSN 1097-6795 ; 0894-7317
    ISSN (online) 1097-6795
    ISSN 0894-7317
    DOI 10.1016/j.echo.2023.10.012
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    In stock of ZB MED Cologne/Königswinter

    Zs.A 2638: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (2.OG)
    ab Jg. 2022: Lesesaal (EG)
    Zs.MG 55: Show issues

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

  7. Article ; Online: Endocrinology of prostate cancer.

    Claessens, Frank / Visakorpi, Tapio

    Molecular and cellular endocrinology

    2018  Volume 462, Issue Pt A, Page(s) 1–2

    MeSH term(s) Androgens/metabolism ; Animals ; Biomarkers, Tumor/metabolism ; DNA Methylation/genetics ; Disease Models, Animal ; Endocrinology ; Humans ; Male ; Prostatic Neoplasms/genetics ; Prostatic Neoplasms/pathology ; RNA, Untranslated/genetics ; RNA, Untranslated/metabolism
    Chemical Substances Androgens ; Biomarkers, Tumor ; RNA, Untranslated
    Language English
    Publishing date 2018-02-20
    Publishing country Ireland
    Document type Editorial ; Introductory Journal Article
    ZDB-ID 187438-x
    ISSN 1872-8057 ; 0303-7207
    ISSN (online) 1872-8057
    ISSN 0303-7207
    DOI 10.1016/j.mce.2018.01.005
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    In stock of ZB MED Cologne/Königswinter

    Zs.A 1127: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (1.OG)
    ab Jg. 2022: Lesesaal (EG)

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

  8. Article ; Online: Re: Molecular Features of Exceptional Response to Neoadjuvant Anti-androgen Therapy in High-risk Localized Prostate Cancer.

    Devlies, Wout / Devos, Gaëtan / Decloedt, Henri / Vansevenant, Bram / Claessens, Frank / Joniau, Steven

    European urology

    2022  Volume 81, Issue 3, Page(s) 314

    MeSH term(s) Androgen Antagonists/therapeutic use ; Humans ; Male ; Neoadjuvant Therapy ; Prostatectomy ; Prostatic Neoplasms/drug therapy ; Prostatic Neoplasms/genetics ; Prostatic Neoplasms/surgery
    Chemical Substances Androgen Antagonists
    Language English
    Publishing date 2022-01-11
    Publishing country Switzerland
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Comment
    ZDB-ID 193790-x
    ISSN 1873-7560 ; 1421-993X ; 0302-2838
    ISSN (online) 1873-7560 ; 1421-993X
    ISSN 0302-2838
    DOI 10.1016/j.eururo.2021.12.027
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    In stock of ZB MED Cologne/Königswinter

    Zs.A 1247: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (1.OG)
    ab Jg. 2022: Lesesaal (EG)
    Zs.MO 294: Show issues

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

  9. Article: Preclinical Models in Prostate Cancer: Resistance to AR Targeting Therapies in Prostate Cancer.

    Devlies, Wout / Handle, Florian / Devos, Gaëtan / Joniau, Steven / Claessens, Frank

    Cancers

    2021  Volume 13, Issue 4

    Abstract: Prostate cancer is an androgen-driven tumor. Different prostate cancer therapies consequently focus on blocking the androgen receptor pathway. Clinical studies reported tumor resistance mechanisms by reactivating and bypassing the androgen pathway. ... ...

    Abstract Prostate cancer is an androgen-driven tumor. Different prostate cancer therapies consequently focus on blocking the androgen receptor pathway. Clinical studies reported tumor resistance mechanisms by reactivating and bypassing the androgen pathway. Preclinical models allowed the identification, confirmation, and thorough study of these pathways. This review looks into the current and future role of preclinical models to understand resistance to androgen receptor-targeted therapies. Increasing knowledge on this resistance will greatly improve insights into tumor pathophysiology and future treatment strategies in prostate cancer.
    Language English
    Publishing date 2021-02-22
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2527080-1
    ISSN 2072-6694
    ISSN 2072-6694
    DOI 10.3390/cancers13040915
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

  10. Article ; Online: The T850D Phosphomimetic Mutation in the Androgen Receptor Ligand Binding Domain Enhances Recruitment at Activation Function 2.

    Helsen, Christine / Nguyen, Tien / Vercruysse, Thomas / Wouters, Staf / Daelemans, Dirk / Voet, Arnout / Claessens, Frank

    International journal of molecular sciences

    2022  Volume 23, Issue 3

    Abstract: Several key functions of the androgen receptor (AR) such as hormone recognition and co-regulator recruitment converge in the ligand binding domain (LBD). Loss- or gain-of-function of the AR contributes to pathologies such as the androgen insensitivity ... ...

    Abstract Several key functions of the androgen receptor (AR) such as hormone recognition and co-regulator recruitment converge in the ligand binding domain (LBD). Loss- or gain-of-function of the AR contributes to pathologies such as the androgen insensitivity syndrome and prostate cancer. Here, we describe a gain-of-function mutation of the surface-exposed threonine at position 850, located at the amino-terminus of Helix 10 (H10) in the AR LBD. Since T850 phosphorylation was reported to affect AR function, we created the phosphomimetic mutation T850D. The AR T850D variant has a 1.5- to 2-fold increased transcriptional activity with no effect on ligand affinity. In the androgen responsive LNCaP cell line grown in medium with low androgen levels, we observed a growth advantage for cells in which the endogenous AR was replaced by AR T850D. Despite the distance to the AF2 site, the AR T850D LBD displayed an increased affinity for coactivator peptides as well as the
    MeSH term(s) Cell Line, Tumor ; Cell Nucleus/metabolism ; Gain of Function Mutation/genetics ; Humans ; Kinetics ; Ligands ; Lysine/metabolism ; Male ; Models, Molecular ; Mutation/genetics ; Phosphorylation ; Protein Binding ; Protein Multimerization ; Protein Structure, Tertiary ; Protein Transport ; Receptors, Androgen/chemistry ; Receptors, Androgen/genetics ; Ubiquitination
    Chemical Substances Ligands ; Receptors, Androgen ; Lysine (K3Z4F929H6)
    Language English
    Publishing date 2022-01-29
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2019364-6
    ISSN 1422-0067 ; 1422-0067 ; 1661-6596
    ISSN (online) 1422-0067
    ISSN 1422-0067 ; 1661-6596
    DOI 10.3390/ijms23031557
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

To top