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The von Hippel-Lindau (VHL) tumor suppressor gene encodes an adaptor protein that regulates an array of transcription-dependent and -independent cellular and physiological processes. Mutations in this gene cause VHL disease, congenital polycythemia, and several sporadic tumor types. The last 15 years of fundamental and clinical research have helped define the phenotypic spectrum of VHL-associated diseases and have introduced new cellular functions for pVHL. Here, we review the current knowledge of VHL function, and the different animal models for VHL disease, with a particular focus on the zebrafish. Zebrafish vhl mutants develop key aspects of the human disease condition, including activation of the hypoxia-inducible factor (HIF) signaling pathway, polycythemia, excessive neovascularization, macular edema, and pronephric abnormalities. The zebrafish vhl model offers a platform for the identification of genetic pathways, modifiers, and interactors involved in the development of VHL-associated neoplasms. Vhl mutants represent a unique and clinically relevant in vivo model for studying genotype-phenotype correlations and the identification of prognostic biomarkers. The amenability of zebrafish for chemical genetic screens will not only be helpful to identify novel therapeutic agents but may also reveal novel processes that require regulation by VHL.
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http://dx.doi.org/10.1016/B978-0-12-381320-6.00007-2 | DOI Listing |
NPJ Digit Med
December 2024
Whoop Inc., Data Science and Research, Boston, MA, USA.
Currently, knowledge of changes in cardiovascular function across the menstrual cycle and how these changes may inform upon underlying health is limited. Utilizing wrist-worn biometric data we developed a novel measure to quantify and investigate the cardiovascular fluctuation (i.e.
View Article and Find Full Text PDFRetin Cases Brief Rep
May 2024
Retina Vitreous Consultants.
Purpose: To demonstrate the response of a juxtapapillary retinal hemangioblastoma (JRH) to belzutifan in a patient with Von-Hippel-Lindau syndrome (VHL).
Methods: This case report includes fundus photography and optical coherence tomography to compare a juxtapapillary retinal hemangioblastoma (JRH) before and 24 months after treatment with belzutifan.
Results: An 18-year-old woman with VHL was diagnosed with a juxtapapillary retinal hemangioblastoma (JRH) at age 13.
Technol Cancer Res Treat
December 2024
Department of Urology, Shanghai Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
Clear cell renal cell carcinoma (ccRCC) is a highly lethal urinary malignancy with poor overall survival (OS) rates. Integrating computer vision and machine learning in pathomics analysis offers potential for enhancing classification, prognosis, and treatment strategies for ccRCC. This study aims to create a pathomics model to predict OS in ccRCC patients.
View Article and Find Full Text PDFACS Pharmacol Transl Sci
December 2024
Vasiliki Sarli - Department of Chemistry, Aristotle University of Thessaloniki, University Campus, Thessaloniki 54124, Greece.
Although small-molecule inhibitors with moderate efficacy targeting MYC have been previously described, to this point, research efforts have failed to bring a suitable small-molecule MYC inhibitor to the clinic. Herein, the discovery of a series of novel MYC degraders bearing VHL to target the "undruggable" MYC is presented. The molecules are based on connecting a known MYC binder to a VHL ligand or pomalidomide to induce MYC degradation in various cancer cells known to express MYC.
View Article and Find Full Text PDFCell Death Dis
December 2024
Department of Gynecology, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai, China.
Poly (ADP-ribose) polymerase 1 (PARP1) catalyzes poly (ADP) ribosylation reaction, one of the essential post-translational modifications of proteins in eukaryotic cells. Given that PARP1 inhibition can lead to synthetic lethality in cells with compromised homologous recombination, this enzyme has been identified as a potent target for anti-cancer therapeutics. However, the clinical application of existing PARP1 inhibitors is restrained by side effects associated with DNA trapping and off-target effects, highlighting the need for improved therapeutic strategies.
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