Publications by authors named "Andrea Valentine"
d-Serine is a coagonist of the -methyl d-aspartate (NMDA) receptor, a key excitatory neurotransmitter receptor. In the brain, d-serine is synthesized from its l-isomer by serine racemase and is metabolized by the D-amino acid oxidase (DAO, DAAO). Many studies have linked decreased d-serine concentration and/or increased DAO expression and enzyme activity to NMDA dysfunction and schizophrenia.
View Article and Find Full Text PDFBackground: Optimising breast cancer treatment remains a challenge. Resistance to therapy is a major problem in both ER- and ER+ breast cancer. Tumour recurrence after chemotherapy and/or targeted therapy leads to more aggressive tumours with enhanced metastatic ability.
View Article and Find Full Text PDFArticle Synopsis
- The ubiquitin proteasome system is emerging as a promising area for drug discovery, particularly targeting ubiquitin specific proteases (USPs) like USP28, which is linked to the c-Myc oncogene.
- Researchers have discovered the first inhibitors of USP28 that selectively bind to it and also affect a closely related enzyme, USP25, while showing minimal impact on other deubiquitinases.
- These inhibitors were found to influence c-Myc levels and induce cancer cell death, though their effectiveness is limited due to a narrow therapeutic window when tested against normal cells.
Purpose: Antiangiogenic therapies can be an important adjunct to the management of many malignancies. Here we investigated a novel protein, FKBPL, and peptide derivative for their antiangiogenic activity and mechanism of action.
Experimental Design: Recombinant FKBPL (rFKBPL) and its peptide derivative were assessed in a range of human microvascular endothelial cell (HMEC-1) assays in vitro.
The HSP90 chaperone and immunophilin FKBPL is an estrogen-responsive gene that interacts with estogen receptor alpha (ERalpha) and regulates its levels. In this study, we explored the effects of FKBPL on breast cancer proliferation. Breast cancer cells stably overexpressing FKBPL became dependent on estrogen for their growth and were dramatically more sensitive to the antiestrogens tamoxifen and fulvestrant, whereas FKBPL knockdown reverses this phenotype.
View Article and Find Full Text PDFArticle Synopsis
- FKBPL is a novel protein involved in the cellular stress response and interacts with components of the heat shock protein 90-glucocorticoid receptor complex.
- The PPIase domain of FKBPL is crucial for its interaction with the dynein motor protein, dynamitin, indicating a specific role in cellular transport and signaling.
- Treatment with dexamethasone prompts FKBPL and the glucocorticoid receptor to move to the nucleus, and FKBPL's presence can enhance glucocorticoid receptor activity, although this effect varies by cell line.
Purpose: A number of cytotoxic chemotherapy agents tested at low concentrations show antiangiogenic properties with limited cytotoxicity, e.g., cyclophosphamide, tirapazamine, and mitoxantrone.
View Article and Find Full Text PDF