Search results for "HERA"
showing 10 items of 14928 documents
Difference in Markers of Microbial Translocation and Cell Apoptosis in HIV Monoinfected and HIV/HCV Coinfected Patients
2019
Abstract Immune activation in human immunodeficiency virus (HIV) infection is driven by microbial translocation and in HIV patients is one of the contributors to faster progression of liver disease along with increased cell apoptosis. The aim of the study was to compare microbial translocation and apoptosis markers in HIV monoinfected and HIV/hepatitis C virus (HCV) coinfected patients, depending on HIV immune status and antiretroviral treatment (ART). We analysed data for 78 HIV monoinfected and 105 HIV/HCV coinfected patients from the Rīga East University Hospital. Lipopolysaccharide (LPS), endotoxin core antibodies (EndoCAb), cytokeratin 18 (CK18) and cyto-chrome c (Cyt-c) levels were me…
Two different pathogenic mechanisms, dying-back axonal neuropathy and pancreatic senescence, are present in the YG8R mouse model of Friedreich ataxia
2016
Frataxin (FXN) deficiency causes Friedreich's ataxia (FRDA), a multisystem disorder with neurological and non-neurological symptoms. FRDA pathophysiology combines developmental and degenerative processes of dorsal root ganglia (DRG), sensory nerves, dorsal columns and other central nervous structures. A dying-back mechanism has been proposed to explain the peripheral neuropathy and neuropathology. In addition, affected individuals have non-neuronal symptoms such as diabetes mellitus or glucose intolerance. To go further in the understanding of the pathogenic mechanisms of neuropathy and diabetes associated with the disease, we have investigated the humanized mouse YG8R model of FRDA. By bio…
Stem Cells and Other Emerging Agents as Innovative "Drugs" in Neurodegenerative Diseases: Benefits and Limitations.
2018
The brain has a limited process of repair/regeneration linked to the restricted and localized activity of neuronal stem cells. Consequently, it shows a reduced capacity to counteract the age-related loss of neural and glial cells and to repair the consequent injuries/lesions of nervous system. This progressively determines nervous dysfunction and onset/progression of neurodegenerative diseases, which represent a serious social (and economic) problem of our populations. Thus, the research of efficient treatments is encouraged. Stem cell therapy might represent a solution. Today, it, indeed, represents the object of intensive research with the hope of using it, in a near future, as effective …
The Role of SVZ Stem Cells in Glioblastoma
2019
As most common primary brain cancer, glioblastoma is also the most aggressive and malignant form of cancer in the adult central nervous system. Glioblastomas are genetic and transcriptional heterogeneous tumors, which in spite of intensive research are poorly understood. Over the years conventional therapies failed to affect a cure, resulting in low survival rates of affected patients. To improve the clinical outcome, an important approach is to identify the cells of origin. One potential source for these are neural stem cells (NSCs) located in the subventricular zone, which is one of two niches in the adult nervous system where NSCs with the capacity of self-renewal and proliferation resid…
Homeostatic interplay between electrical activity and neuronal apoptosis in the developing neocortex
2017
An intriguing feature of nervous system development in most animal species is that the initial number of generated neurons is higher than the number of neurons incorporated into mature circuits. A substantial portion of neurons is indeed eliminated via apoptosis during a short time window - in rodents the first two postnatal weeks. While it is well established that neurotrophic factors play a central role in controlling neuronal survival and apoptosis in the peripheral nervous system (PNS), the situation is less clear in the central nervous system (CNS). In postnatal rodent neocortex, the peak of apoptosis coincides with the occurrence of spontaneous, synchronous activity patterns. In this …
Profilin 1 delivery tunes cytoskeletal dynamics toward CNS axon regeneration
2020
After trauma, regeneration of adult CNS axons is abortive, causing devastating neurologic deficits. Despite progress in rehabilitative care, there is no effective treatment that stimulates axonal growth following injury. Using models with different regenerative capacities, followed by gain- and loss-of-function analysis, we identified profilin 1 (Pfn1) as a coordinator of actin and microtubules (MTs), powering axonal growth and regeneration. In growth cones, Pfn1 increased actin retrograde flow, MT growth speed, and invasion of filopodia by MTs, orchestrating cytoskeletal dynamics toward axonal growth. In vitro, active Pfn1 promoted MT growth in a formin-dependent manner, whereas localizati…
Role of RAS mutation status as a prognostic factor for patients with advanced colorectal cancer treated with first-line chemotherapy based on fluorop…
2016
The role of Kirsten rat sarcoma viral oncogene homolog (KRAS) and neuroblastoma RAS viral oncogene homolog (NRAS) mutations as negative predictors for anti-epidermal growth factor receptor (EGFR) therapies in metastatic colorectal cancer (CRC) has been firmly established. However, whether the RAS mutation status plays a role as a biomarker for anti-vascular endothelial growth factor (VEGF) treatment remains controversial. Data from 93 CRC patients who received first-line cytotoxic chemotherapy with fluoropyrimidines and oxaliplatin, with or without bevacizumab, were analyzed. We investigated the association between the RAS mutation status and clinical outcomes in terms of response rate, pro…
How to Deal with Second Line Dilemma in Metastatic Colorectal Cancer? A Systematic Review and Meta-Analysis
2019
Monoclonal antibodies targeting epidermal growth factor receptor (EGFR) or vascular endothelial growth factor (VEGF) have demonstrated efficacy with chemotherapy (CT) as second line treatment for metastatic colorectal cancer (mCRC). The right sequence of the treatments in all RAS (KRAS/NRAS) wild type (wt) patients has not precisely defined. We evaluated the impact of aforementioned targeted therapies in second line setting, analyzing efficacy and safety data from phase III clinical trials. We performed both direct and indirect comparisons between anti-EGFR and anti-VEGF. Outcomes included disease control rate (DCR), objective response rate (ORR), progression-free survival (PFS), overall su…
Impact of BRAF and RAS mutations on first-line efficacy of FOLFIRI plus cetuximab versus FOLFIRI plus bevacizumab: analysis of the FIRE-3 (AIO KRK-03…
2017
Abstract Background RAS and BRAF mutations have been identified as negative prognostic factors in metastatic colorectal cancer. Efficacy of 5-fluorouracil, leucovorin, irinotecan (FOLFIRI) plus bevacizumab in patients with RAS-mutant tumours needs to be further evaluated. Whether to treat patients with BRAF-mutant tumours with either bevacizumab or anti-epidermal growth factor receptor (EGFR) antibodies remains unclear. Methods Patients treated within the FIRE-3 trial were retrospectively tested for BRAF and RAS mutations using formalin fixated paraffin embedded (FFPE) tumour material applying pyrosequencing for KRAS and NRAS exon 2, 3 and 4 mutations as far as for BRAF mutations. Survival …
Does bevacizumab impact anti-EGFR therapy efficacy in metastatic colorectal cancer?
2016
IF 5.008; International audience; Anti-EGFR therapy and antiangiogenic therapies are used alone or in combination with chemotherapies to improve survival in metastatic colorectal cancer. However, it is unknown whether pretreatment with antiangiogenic therapy could impact on the efficacy of anti-EGFR therapy. We selected one hundred and twenty eight patients diagnosed with advanced colorectal cancer with a KRAS and NRAS unmutated tumor. These patients were treated with cetuximab or panitumumab alone or with chemotherapy as second or third-line. Univariate and multivariate Cox model analysis were performed to estimate the effect of a previous bevacizumab regimen on progression free survival a…