ORCID Profile
0000-0003-3691-6419
Current Organisation
Universidade de Santiago de Compostela
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Publisher: Springer Science and Business Media LLC
Date: 23-05-2004
DOI: 10.1038/NG1367
Publisher: Springer Science and Business Media LLC
Date: 04-02-2008
DOI: 10.1038/ONC.2008.7
Abstract: Acute promyelocytic leukemia is associated with chromosomal translocations that involve the RARalpha gene and several distinct loci producing a variety of fusion proteins. One such fusion partner is promyelocytic leukemia zinc-finger gene (PLZF), a member of the POK (POZ and Krüppel) family of transcriptional repressors that is a key developmental regulator, stem cell maintenance factor and tumor suppressor. Overexpression of PLZF has been shown to induce cell cycle arrest at the G(1) to S transition and repress the expression of key pro-proliferative genes such as CCNA2 and MYC. However, given this data suggesting an important growth inhibitory role for PLZF, relatively little is known regarding regulation of its activity. Here we show that the main cyclin-dependent kinase involved at the G(1) to S transition (CDK2) phosphorylates PLZF at two consensus sites found within PEST domains present in the hinge region of the protein. This phosphorylation triggers the ubiquitination and subsequent degradation of PLZF, which impairs PLZF transcriptional repression ability and antagonizes its growth inhibitory effects. This critical mechanism of PLZF regulation may thus be relevant for cell cycle progression during the development and the pathogenesis of human cancer.
Publisher: Informa UK Limited
Date: 12-2004
Publisher: MDPI AG
Date: 18-12-2018
Abstract: Glioblastoma (GB) is the most aggressive and most common malignant primary brain tumor diagnosed in adults. GB shows a poor prognosis and, unfortunately, current therapies are unable to improve its clinical outcome, imposing the need for innovative therapeutic approaches. The main reason for the poor prognosis is the great cell heterogeneity of the tumor mass and its high capacity for invading healthy tissues. Moreover, the glioblastoma microenvironment is capable of suppressing the action of the immune system through several mechanisms such as recruitment of cell modulators. Development of new therapies that avoid this immune evasion could improve the response to the current treatments for this pathology. Natural Killer (NK) cells are cellular components of the immune system more difficult to deceive by tumor cells and with greater cytotoxic activity. Their use in immunotherapy gains strength because they are a less toxic alternative to existing therapy, but the current research focuses on mimicking the NK attack strategy. Here, we summarize the most recent studies regarding molecular mechanisms involved in the GB and immune cells interaction and highlight the relevance of NK cells in the new therapeutic challenges.
Publisher: Elsevier BV
Date: 08-2022
DOI: 10.1016/J.ACA.2022.340084
Abstract: The development of new diagnostic tools in tumor pathology allows the optimization of in idualized therapies in cancer patients. The functional optical image provides a unique opportunity to identify the pathophysiological characteristics of each tumor in a non-invasive way. Although fluorescent recombinant affibodies and nanobodies, capable of detecting certain membrane proteins present in tumor cells, has been described, the use of bioluminescent molecules is gaining a great impact in this field due to its high sensitivity. In this work, we characterize a new luciferase from the Metridia lucens copepod (MlLuc) and develop a novel bioluminescent recombinant affibody (MlLuc-aff) capable of recognizing the HER2 receptors that are overexpressed in breast cancer tumors. For this purpose, the thermostability and pH sensitivity of MlLuc1.1 were determined, showing no significant changes in the activity among temperatures between 4 and 70 °C, and with a maximum of brightness at pH 8.0. Furthermore, MlLuc-aff was able to accurately detect HER2 receptors expressed in the SK-BR-3 cells. Future applications of this new tracer can contribute to the early diagnosis of breast cancer patients and the assessment of the efficacy of the treatment.
Location: United States of America
No related grants have been discovered for Jose A. Costoya.