70 research outputs found
Corneal retardation time as an ocular hypertension disease indicator
Objective. A detailed analysis of the corneal retardation time as a
highly related parameter to the intraocular pressure (IOP), and its plausible
role as an indicator of ocular hypertension disease. Approach. A simple
theoretical expression for is derived within the corneal viscoelastic
model of Kelvin-Voigt with 3 elements. This retardation time can be easily
calculated from the well-known signal and pressure amplitudes of non-contact
tonometers like the Ocular Response Analyzer (ORA). Then, a population-based
study was performed where 100 subjects aged from 18 to 30 were analyzed (within
this group, about 10% had an elevated IOP with more than 21 mmHg). Main
results. A clear relationship between the corneal retardation time and the
corneal-compensated intraocular pressure was found, underlying the risk for
ocular hypertensive (OHT) subjects with lower values to develop
hypertension illnesses (due to the inability of poorly viscoelastic corneas to
absorb IOP fluctuations, resulting in probable optic nerve damage).
Significance. Our results might provide an useful tool to systematically
discern which OHT patients (and even those with normal IOP values) are more
likely to suffer glaucoma progression and, consequently, ensure an early
diagnosis.Comment: Accepted for publication in Biomedical Physics and Engineering
Expres
SEOM-GEINO clinical guidelines for high-grade gliomas of adulthood (2022)
High-grade gliomas (HGG) are the most common primary brain malignancies and account for more than half of all malignant primary brain tumors. The new 2021 WHO classification divides adult HGG into four subtypes: grade 3 oligodendroglioma (1p/19 codeleted, IDH-mutant); grade 3 IDH-mutant astrocytoma; grade 4 IDH-mutant astrocytoma, and grade 4 IDH wild-type glioblastoma (GB). Radiotherapy (RT) and chemotherapy (CTX) are the current standard of care for patients with newly diagnosed HGG. Several clinically relevant molecular markers that assist in diagnosis and prognosis have recently been identified. The treatment for recurrent high-grade gliomas is not well defined and decision-making is usually based on prior strategies, as well as several clinical and radiological factors. Whereas the prognosis for GB is grim (5-year survival rate of 5-10%) outcomes for the other high-grade gliomas are typically better, depending on the molecular features of the tumor. The presence of neurological deficits and seizures can significantly impact quality of life
In silico validation of RNA-Seq results can identify gene fusions with oncogenic potential in glioblastoma
RNA-Sequencing (RNA-Seq) can identify gene fusions in tumors, but not all these fusions have functional consequences. Using multiple data bases, we have performed an in silico analysis of fusions detected by RNA-Seq in tumor samples from 139 newly diagnosed glioblastoma patients to identify in-frame fusions with predictable oncogenic potential. Among 61 samples with fusions, there were 103 different fusions, involving 167 different genes, including 20 known oncogenes or tumor suppressor genes (TSGs), 16 associated with cancer but not oncogenes or TSGs, and 32 not associated with cancer but previously shown to be involved in fusions in gliomas. After selecting in-frame fusions able to produce a protein product and running Oncofuse, we identified 30 fusions with predictable oncogenic potential and classified them into four non-overlapping categories: six previously described in cancer; six involving an oncogene or TSG; four predicted by Oncofuse to have oncogenic potential; and 14 other in-frame fusions. Only 24 patients harbored one or more of these 30 fusions, and only two fusions were present in more than one patient: FGFR3::TACC3 and EGFR::SEPTIN14. This in silico study provides a good starting point for the identification of gene fusions with functional consequences in the pathogenesis or treatment of glioblastoma
Gal-1 Expression Analysis in the GLIOCAT Multicenter Study: Role as a Prognostic Factor and an Immune-Suppressive Biomarker
Glioblastoma (GBM) is the most frequent primary malignant brain tumor and has a dismal prognosis. Unfortunately, despite the recent revolution of immune checkpoint inhibitors in many solid tumors, these have not shown a benefit in overall survival in GBM patients. Therefore, new potential treatment targets as well as diagnostic, prognostic, and/or predictive biomarkers are needed to improve outcomes in this population. The beta-galactoside binding protein Galectin-1 (Gal-1) is a protein with a wide range of pro-tumor functions such as proliferation, invasion, angiogenesis, and immune suppression. Here, we evaluated Gal-1 expression by immunohistochemistry in a homogenously treated cohort of GBM (the GLIOCAT project) and correlated its expression with clinical and molecular data. We observed that Gal-1 is a negative prognostic factor in GBM. Interestingly, we observed higher levels of Gal-1 expression in the mesenchymal/classical subtypes compared to the less aggressive proneural subtype. We also observed a Gal-1 expression correlation with immune suppressive signatures of CD4 T-cells and macrophages, as well as with several GBM established biomarkers, including SHC1, PD-L1, PAX2, MEOX2, YKL-40, TCIRG1, YWHAG, OLIG2, SOX2, Ki-67, and SOX11. Moreover, Gal-1 levels were significantly lower in grade 4 IDH-1 mutant astrocytomas, which have a better prognosis. Our results confirm the role of Gal-1 as a prognostic factor and also suggest its value as an immune-suppressive biomarker in GBM
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