A5036631927- T-cell and Retrovirus Studies
- Estrogen and related hormone effects
- Cancer-related gene regulation
- Ubiquitin and proteasome pathways
- Acute Lymphoblastic Leukemia research
- Lymphoma Diagnosis and Treatment
- Cell death mechanisms and regulation
- Toxin Mechanisms and Immunotoxins
- Cancer-related Molecular Pathways
- Peptidase Inhibition and Analysis
- Epigenetics and DNA Methylation
- Cancer, Hypoxia, and Metabolism
- Chronic Lymphocytic Leukemia Research
- RNA modifications and cancer
- Cancer, Lipids, and Metabolism
- NF-κB Signaling Pathways
- Cancer Cells and Metastasis
- S100 Proteins and Annexins
- Chronic Myeloid Leukemia Treatments
- Immune cells in cancer
- Signaling Pathways in Disease
- TGF-β signaling in diseases
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- HER2/EGFR in Cancer Research
- Amyloidosis: Diagnosis, Treatment, Outcomes
Universidad Autónoma de Madrid
2011-2024
Centro de Biología Molecular Severo Ochoa
2012-2024
Consejo Superior de Investigaciones Científicas
2009-2024
Hospital Universitario Fundación Jiménez Díaz
2016-2023
Instituto de Investigación de Enfermedades Raras
2009-2023
Centre for Biomedical Network Research on Rare Diseases
2012-2019
Centro de Investigación Biomédica en Red
2016-2019
Research Institute Hospital 12 de Octubre
2015
Ikerbasque
2015
Biogipuzkoa Health Research Institute
2015
Pharmacological activation of cannabinoid receptors elicits antitumoral responses in different cancer models. However, the biological role these tumor physio-pathology is still unknown. We analyzed CB2 receptor protein expression two series 166 and 483 breast samples operated University Hospitals Kiel, Tübingen, Freiburg between 1997 2010 mRNA previously published DNA microarray datasets. The oncogenesis was studied by generating a mouse line that expresses human V-Erb-B2 Avian...
Abstract Fusions transcripts have been proven to be strong drivers for neoplasia-associated mutations, although their incidence in T-cell lymphoblastic lymphoma needs determined yet. Using RNA-Seq we selected 55 fusion identified by at least two of three detection methods the same tumour. We confirmed existence 24 predicted novel fusions that had not described cancer or normal tissues yet, indicating accuracy prediction. Of note, one them involves proto oncogene TAL1 . Other could explain...
Abstract Clinical management of breast cancer (BC) metastasis remains an unmet need as it accounts for 90% BC-associated mortality. Although the luminal subtype, which represents >70% BC cases, is generally associated with a favorable outcome, susceptible to metastatic relapse late 15 years after treatment discontinuation. Seeking therapeutic approaches well screening tools properly identify those patients higher risk recurrence therefore essential. Here, we report that lipid-degrading...
Abstract Endoglin is a membrane glycoprotein that acts as coreceptor for transforming growth factor-β. We and others have previously suggested function of endoglin tumor suppressor in epithelial cancer. Here, we study the expression during chemical mouse skin carcinogenesis. find shedding endoglin, allowing secretion soluble form, late event associated with progression from squamous to spindle cell carcinomas. Knockdown transformed keratinocytes activates Smad2/3 signaling pathway resulting...
The JAK-STAT pathway has a substantial role in lymphoid precursor cell proliferation, survival and differentiation. Nonetheless, the contribution of JAK2 to T-cell lymphoblastic lymphoma (T-LBL) development remains poorly understood. We have identified one activating TEL-JAK2 translocation four missense mutations accumulated 2 out 16 T-LBL samples. Two them are novel other two reported for first time T-LBL. Notably, R683G I682T might arisen owing RNA editing. Mutated samples showed different...
Cryptic deletions at chromosome 6q are common cytogenetic abnormalities in T-cell lymphoblastic leukemia/lymphoma (T-LBL), but the target genes have not been formally identified. Our results build on detection of specific chromosomal losses a mouse model γ-radiation-induced T-LBLs and provide interesting clues for new putative susceptibility region orthologous to human 6q15–6q16.3. Among these, Epha7 emerges as bona fide candidate tumor suppressor gene because it is inactivated practically...
Inappropriate activation of the GLI/hedgehog (GLI/Hh) signalling occurs in several human cancers, including haematological neoplasms. However, little is known about its relevance precursor T-cell lymphoblastic lymphomas (T-LBL) development. Moreover, mechanisms whereby GLI/Hh activated malignancies are not fully clear. Here, we show that gene Smoothened ( SMO ), only non-redundant this pathway, up-regulated mouse and T-LBL. Interestingly, down-regulation micro-RNAs mmu-miR-30a mmu-miR-141 as...
The acquisition of resistance towards FAS-mediated apoptosis may be required for tumor formation. Tumors from various histological origins exhibit FAS mutations, the most frequent being hematological malignancies. However, data regarding mutations or signaling alterations are still lacking in precursor T-cell lymphoblastic lymphomas (T-LBLs). available on acute leukemia, origin as well, indicate a low frequency but often report serious reduction well chemoresistance, thus suggesting...
T-cell lymphoblastic lymphoma is a haematological disease with an urgent need for reliable prognostic biomarkers that allow therapeutic stratification and dose adjustment. The scarcity of human samples responsible the delayed progress in study clinical management this disease, especially compared acute leukaemia, its leukemic counterpart. In present work, we have determined by immunohistochemistry S194-P-FADD protein significantly reduced cohort 22 from lymphoma. Notably, extent such...
Summary Despite the Janus kinase/signal transducers and activators of transcription (JAK/STAT) pathway being frequently altered in T‐ALL/LBL, no specific therapy has been approved for T‐ALL/LBL patients with constitutive signalling by JAK/STAT, so there is an urgent need to identify members that may be potential therapeutic targets. In present study, we searched JAK/STAT potentially modulated through aberrant methylation identified SOCS3 hypermethylation as a recurrent event T‐ALL/LBL....
In previous reports, we described germ line functional polymorphisms that differentiate Fas and FasL genes in two mouse strains (SEG/Pas C57BL/6J) exhibiting extreme differences susceptibility to γ radiation-induced T-cell lymphomas. Here, provide new data reinforcing the importance of extrinsic pathway apoptosis mediated by lymphoma development about significance located at intracellular extracellular domains . Using DNA recombinant technology, generate chimerical proteins combination...
Cancer susceptibility is essentially attributable to multiple low-penetrance genes. Using interspecific consomic and congenic mice between the tumor-resistant SEG/Pas tumor-sensitive C57BL/6J strains, a region on chromosome 19 involved in genetic resistance gamma-irradiation-induced T-cell lymphomas (Tlyr1) has been identified. Through development of nonoverlapping subcongenic it further shown that Anxa1 may be candidate gene basis its differential expression thymus stroma cells after...
Precursor T-cell lymphoblastic lymphomas (T-LBL) are rare aggressive hematological malignancies that mainly develop in children. As other cancers, the loss of cell cycle control plays a prominent role pathogenesis these is primarily attributed to CDKN2A (encoding protein p16INK4A). However, impact deregulation genes such as CDKN1C, E2F1, and TP53 remains be clarified. Interestingly, experiments mouse models have proven conditional specific deletion Cdkn1c gene may induce differentiation...
In the present work, we show that T-cell lymphoblastic lymphoma cells exhibit a reduction of FADD availability in cytoplasm, which may contribute to impaired apoptosis. addition, observe phosphorylation inversely correlates with proliferation capacity and tumor aggressiveness. The resultant balance between FADD-dependent apoptotic non-apoptotic abilities define outcome tumor. Thus, propose expression can be reliable biomarkers prognostic value for T-LBL stratification.
Abstract The Fas/FasL system mediates induced apoptosis of immature thymocytes and peripheral T lymphocytes, but little is known about its implication in genetic susceptibility to T-cell malignancies. In this article, we report that the expression FasL increases early all mice after γ-radiation treatments, maintaining such high levels for a long time resisted tumor induction. However, practically absent lymphoblastic lymphomas. Interestingly, there exist significant differences level between...
The standard-of-care treatment of T-cell acute lymphoblastic leukaemia (T-ALL) with chemotherapy usually achieves reasonable rates initial complete response. However, patients who relapse or do not respond to conventional therapy show dismal outcomes, cure below 10% and limited therapeutic options. To ameliorate the clinical management these patients, it is urgent identify biomarkers able predict their outcomes. In this work, we investigate whether NRF2 activation constitutes a biomarker...
Precursor T-cell lymphoblastic neoplasms are aggressive malignancies in need for more effective and specific therapeutic treatments. A significant fraction of these harbor deletions on the locus 9p21, targeting tumor suppressor CDKN2A but also deleting aconitase 1 (ACO1) gene, a neighboring housekeeping gene involved cytoplasm mitochondrial metabolism. Here we show that reducing activity with fluorocitrate decreases viability neoplasia cells correlation to differential expression. The...
Abstract Precursor T-cell neoplasms (T-ALL/LBL) are aggressive hematological malignancies that arise from the malignant transformation of immature thymocytes. Despite JAK/STAT pathway is recurrently altered in these neoplasms, there not pharmacological inhibitors officially approved for treatment T-ALL/LBL patients present oncogenic mutations. In effort to identify potential therapeutic targets those patients, we followed an alternative approach and focused on their transcriptional profile....