Institution
Hebron University
Education•Hebron, Palestinian Territory•
About: Hebron University is a education organization based out in Hebron, Palestinian Territory. It is known for research contribution in the topics: Population & Cancer. The organization has 2714 authors who have published 4180 publications receiving 163736 citations.
Papers published on a yearly basis
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TL;DR: Genetic changes affecting TP53, RB1, PTEN, MED12, YWHAE and VIPR2 were present in the majority of uLMS, and data suggest that VIPR 2, which is a negative regulator of smooth muscle cell proliferation, might be a novel tumor suppressor gene in uL MS.
Abstract: Uterine leiomyosarcomas (uLMS) are rare, aggressive malignancies for which limited treatment options are available. To gain novel molecular insights into uLMS and identify potential novel therapeutic targets, we characterized 84 uLMS samples for genome-wide somatic copy number alterations, mutations, gene fusions and gene expression and performed a data integration analysis. We found that alterations affecting TP53, RB1, PTEN, MED12, YWHAE and VIPR2 were present in the majority of uLMS. Pathway analyses additionally revealed that the PI3K/AKT/mTOR, estrogen-mediated S-phase entry and DNA damage response signaling pathways, for which inhibitors have already been developed and approved, frequently harbored genetic changes. Furthermore, a significant proportion of uLMS was characterized by amplifications and overexpression of known oncogenes (CCNE1, TDO2), as well as deletions and reduced expression of tumor suppressor genes (PTEN, PRDM16). Overall, it emerged that the most frequently affected gene in our uLMS samples was VIPR2 (96%). Interestingly, VIPR2 deletion also correlated with unfavorable survival in uLMS patients (multivariate analysis; HR = 4.5, CI = 1.4-14.3, p = 1.2E-02), while VIPR2 protein expression was reduced in uLMS vs. normal myometrium. Moreover, stimulation of VIPR2 with its natural agonist VIP decreased SK-UT-1 uLMS cell proliferation in a dose-dependent manner. These data suggest that VIPR2, which is a negative regulator of smooth muscle cell proliferation, might be a novel tumor suppressor gene in uLMS. Our work further highlights the importance of integrative molecular analyses, through which we were able to uncover the genes and pathways most frequently affected by somatic alterations in uLMS.
63 citations
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University of California, San Diego1, University of Milan2, Yale University3, University of Lyon4, University of Duisburg-Essen5, Katholieke Universiteit Leuven6, University of Barcelona7, Hebron University8, Harvard University9, Brigham and Women's Hospital10, Boehringer Ingelheim11, Université catholique de Louvain12, Cliniques Universitaires Saint-Luc13
TL;DR: Subgroups of HNSCC patients who may achieve increased benefit from afatinib were identified based on prespecified tumor biomarkers (p16-negative, EGFR-amplified, HER3-low, PTEN-high), and future studies are warranted to validate these findings.
63 citations
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TL;DR: Overall, these findings indicate that the plasma-based BEAMing assay is a viable solution for rapid delivery of RAS mutation status to determine mCRC patient eligibility for anti-EGFR therapy.
Abstract: Liquid biopsy offers a minimally invasive alternative to tissue-based evaluation of mutational status in cancer. The goal of the present study was to evaluate the aggregate performance of OncoBEAM RAS mutation analysis in plasma of colorectal cancer (CRC) patients at 10 hospital laboratories in Spain where this technology is routinely implemented. Circulating cell-free DNA from plasma was examined for RAS mutations using the OncoBEAM platform at each hospital laboratory. Results were then compared to those obtained from DNA extracted from tumour tissue from the same patient. The overall percentage agreement between plasma-based and tissue-based RAS mutation testing of the 236 participants was 89% (210/236; kappa, 0.770 (95% CI: 0.689–0.852)). Re-analysis of tissue from all discordant cases by BEAMing revealed two false negative and five false positive tumour tissue RAS results, with a final concordance of 92%. Plasma false negative results were found more frequently in patients with exclusive lung metastatic disease. In this first prospective real-world RAS mutation performance comparison study, a high overall agreement was observed between results obtained from plasma and tissue samples. Overall, these findings indicate that the plasma-based BEAMing assay is a viable solution for rapid delivery of RAS mutation status to determine mCRC patient eligibility for anti-EGFR therapy.
63 citations
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TL;DR: Fusobacterium nucleatum persistence post-nCRT is associated with high relapse rates in LARC, potentially linked to suppression of immune cytotoxicity.
63 citations
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TL;DR: Evaluating the prospects of future therapeutic strategies, which focus on dendritic cells anddendritic cell-related targets to treat MS, finds that novel strategies that can regulate dendrite cell development and differentiation and harness the tolerogenic capacity of these cells are being developed.
Abstract: Multiple sclerosis (MS) is considered to be a predominantly T-cell-mediated disease, and emerging evidence indicates that dendritic cells have a critical role in the initiation and progression of this debilitating condition. Dendritic cells are specialized antigen-presenting cells that can prime naive T cells and modulate adaptive immune responses. Their powerful biological functions indicate that these cells can be exploited by immunotherapeutic approaches. Therapies that inhibit the immunogenic actions of dendritic cells through the blockade of proinflammatory cytokine production and T cell co-stimulatory pathways are currently being pursued. Furthermore, novel strategies that can regulate dendritic cell development and differentiation and harness the tolerogenic capacity of these cells are also being developed. Here, we evaluate the prospects of these future therapeutic strategies, which focus on dendritic cells and dendritic cell-related targets to treat MS.
63 citations
Authors
Showing all 2723 results
Name | H-index | Papers | Citations |
---|---|---|---|
José Baselga | 156 | 707 | 122498 |
M. I. Martínez | 134 | 1251 | 79885 |
Josep Tabernero | 111 | 803 | 68982 |
Jordi Rello | 103 | 694 | 35994 |
Xavier Montalban | 95 | 762 | 52842 |
James M. Downey | 91 | 381 | 29506 |
Enriqueta Felip | 83 | 622 | 53364 |
Joaquim Bellmunt | 82 | 660 | 41472 |
Joan Montaner | 80 | 489 | 22413 |
Marc Miravitlles | 76 | 651 | 25671 |
David H. Salat | 75 | 241 | 36779 |
Eduard Gratacós | 75 | 531 | 20178 |
Alex Rovira | 74 | 356 | 19586 |
Ramon Bataller | 72 | 283 | 19316 |
Maria Buti | 71 | 493 | 26596 |