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21.
Carlos Garcia-Padilla Estefanía Lozano-Velasco María del Mar Muoz-Gallardo Juan Manuel Castillo-Casas Sheila Cao-Carrillo Francisco Jos Martínez-Amaro Virginio García-Lpez Amelia Arnega Diego Franco Virginio García-Martínez Carmen Lpez-Snchez 《International journal of molecular sciences》2022,23(15)
Various treatments based on drug administration and radiotherapy have been devoted to preventing, palliating, and defeating cancer, showing high efficiency against the progression of this disease. Recently, in this process, malignant cells have been found which are capable of triggering specific molecular mechanisms against current treatments, with negative consequences in the prognosis of the disease. It is therefore fundamental to understand the underlying mechanisms, including the genes—and their signaling pathway regulators—involved in the process, in order to fight tumor cells. Long non-coding RNAs, H19 in particular, have been revealed as powerful protective factors in various types of cancer. However, they have also evidenced their oncogenic role in multiple carcinomas, enhancing tumor cell proliferation, migration, and invasion. In this review, we analyze the role of lncRNA H19 impairing chemo and radiotherapy in tumorigenesis, including breast cancer, lung adenocarcinoma, glioma, and colorectal carcinoma. 相似文献
22.
Francisco J. Osuna-Prieto Francisco M. Acosta Unai A. Perez de Arrilucea Le Floch Blanca Riquelme-Gallego Elisa Merchan-Ramirez Huiwen Xu Juan Carlos De La Cruz-Mrquez Francisco J. Amaro-Gahete Jose A. Llamas-Elvira Eva M. Trivio-Ibez Antonio Segura-Carretero Jonatan R Ruiz 《Journal of the International Society of Sports Nutrition》2022,19(1):417
23.
Javier Simarro Gema Prez-Sim Nuria Mancheo Emilio Ansotegui Carlos Francisco Muoz-Núez Jos Gmez-Codina
scar Juan Sarai Palanca 《International journal of molecular sciences》2022,23(15)
In pretreatment tumor samples of EGFR-mutated non-small cell lung cancer (NSCLC) patients, EGFR-Thr790Met mutation has been detected in a variable prevalence by different ultrasensitive assays with controversial prognostic value. Furthermore, its detection in liquid biopsy (LB) samples remains challenging, being hampered by the shortage of circulating tumor DNA (ctDNA). Here, we describe the technical validation and clinical implications of a real-time PCR with peptide nucleic acid (PNA-Clamp) and digital droplet PCR (ddPCR) for EGFR-Thr790Met detection in diagnosis FFPE samples and in LB. Limit of blank (LOB) and limit of detection (LOD) were established by analyzing negative and low variant allele frequency (VAF) FFPE and LB specimens. In a cohort of 78 FFPE samples, both techniques showed an overall agreement (OA) of 94.20%. EGFR-Thr790Met was detected in 26.47% of cases and was associated with better progression-free survival (PFS) (16.83 ± 7.76 vs. 11.47 ± 1.83 months; p = 0.047). In LB, ddPCR was implemented in routine diagnostics under UNE-EN ISO 15189:2013 accreditation, increasing the detection rate of 32.43% by conventional methods up to 45.95%. During follow-up, ddPCR detected EGFR-Thr790Met up to 7 months before radiological progression. Extensively validated ultrasensitive assays might decipher the utility of pretreatment EGFR-Thr790Met and improve its detection rate in LB studies, even anticipating radiological progression. 相似文献
24.
Sandra Brasil Mariateresa Allocca Salvador C. M. Magrinho Inês Santos Madalena Raposo Rita Francisco Carlota Pascoal Tiago Martins Paula A. Videira Florbela Pereira Giuseppina Andreotti Jaak Jaeken Kristin A. Kantautas Ethan O. Perlstein Vanessa dos Reis Ferreira 《International journal of molecular sciences》2022,23(15)
Advances in research have boosted therapy development for congenital disorders of glycosylation (CDG), a group of rare genetic disorders affecting protein and lipid glycosylation and glycosylphosphatidylinositol anchor biosynthesis. The (re)use of known drugs for novel medical purposes, known as drug repositioning, is growing for both common and rare disorders. The latest innovation concerns the rational search for repositioned molecules which also benefits from artificial intelligence (AI). Compared to traditional methods, drug repositioning accelerates the overall drug discovery process while saving costs. This is particularly valuable for rare diseases. AI tools have proven their worth in diagnosis, in disease classification and characterization, and ultimately in therapy discovery in rare diseases. The availability of biomarkers and reliable disease models is critical for research and development of new drugs, especially for rare and heterogeneous diseases such as CDG. This work reviews the literature related to repositioned drugs for CDG, discovered by serendipity or through a systemic approach. Recent advances in biomarkers and disease models are also outlined as well as stakeholders’ views on AI for therapy discovery in CDG. 相似文献
25.
Sara Garcinuo Francisco Javier Gil-Etayo Esther Mancebo Marta Lpez-Nevado Antonio Lalueza Raquel Díaz-Simn Daniel Enrique Pleguezuelo Manuel Serrano Oscar Cabrera-Marante Luis M. Allende Estela Paz-Artal Antonio Serrano 《International journal of molecular sciences》2022,23(12)
NK degranulation plays an important role in the cytotoxic activity of innate immunity in the clearance of intracellular infections and is an important factor in the outcome of the disease. This work has studied NK degranulation and innate immunological profiles and functionalities in COVID-19 patients and its association with the severity of the disease. A prospective observational study with 99 COVID-19 patients was conducted. Patients were grouped according to hospital requirements and severity. Innate immune cell subpopulations and functionalities were analyzed. The profile and functionality of innate immune cells differ between healthy controls and severe patients; CD56dim NK cells increased and MAIT cells and NK degranulation rates decreased in the COVID-19 subjects. Higher degranulation rates were observed in the non-severe patients and in the healthy controls compared to the severe patients. Benign forms of the disease had a higher granzymeA/granzymeB ratio than complex forms. In a multivariate analysis, the degranulation capacity resulted in a protective factor against severe forms of the disease (OR: 0.86), whereas the permanent expression of NKG2D in NKT cells was an independent risk factor (OR: 3.81; AUC: 0.84). In conclusion, a prompt and efficient degranulation functionality in the early stages of infection could be used as a tool to identify patients who will have a better evolution. 相似文献
26.
María Luisa Roldn Gema Lizbeth Ramírez-Salinas Marlet Martinez-Archundia Francisco Cuellar-Perez Claudia Andrea Vilchis-Nestor Juan Carlos Cancino-Diaz Liora Shoshani 《International journal of molecular sciences》2022,23(14)
The β2 subunit of Na+, K+-ATPase was originally identified as the adhesion molecule on glia (AMOG) that mediates the adhesion of astrocytes to neurons in the central nervous system and that is implicated in the regulation of neurite outgrowth and neuronal migration. While β1 isoform have been shown to trans-interact in a species-specific mode with the β1 subunit on the epithelial neighboring cell, the β2 subunit has been shown to act as a recognition molecule on the glia. Nevertheless, none of the works have identified the binding partner of β2 or described its adhesion mechanism. Until now, the interactions pronounced for β2/AMOG are heterophilic cis-interactions. In the present report we designed experiments that would clarify whether β2 is a cell–cell homophilic adhesion molecule. For this purpose, we performed protein docking analysis, cell–cell aggregation, and protein–protein interaction assays. We observed that the glycosylated extracellular domain of β2/AMOG can make an energetically stable trans-interacting dimer. We show that CHO (Chinese Hamster Ovary) fibroblasts transfected with the human β2 subunit become more adhesive and make large aggregates. The treatment with Tunicamycin in vivo reduced cell aggregation, suggesting the participation of N-glycans in that process. Protein–protein interaction assay in vivo with MDCK (Madin-Darby canine kidney) or CHO cells expressing a recombinant β2 subunit show that the β2 subunits on the cell surface of the transfected cell lines interact with each other. Overall, our results suggest that the human β2 subunit can form trans-dimers between neighboring cells when expressed in non-astrocytic cells, such as fibroblasts (CHO) and epithelial cells (MDCK). 相似文献
27.
Tnia Cemeli Marta Guasch-Valls Marina Ribes-Santolaria Eva Ibars Raúl Navaridas Xavier Dolcet Neus Pedraza Neus Colomina Jordi Torres-Rosell Francisco Ferrezuelo Judit Herreros Eloi Garí 《International journal of molecular sciences》2022,23(15)
Glioblastoma (GBM) is the most common tumor in the central nervous system in adults. This neoplasia shows a high capacity of growth and spreading to the surrounding brain tissue, hindering its complete surgical resection. Therefore, the finding of new antitumor therapies for GBM treatment is a priority. We have previously described that cyclin D1-CDK4 promotes GBM dissemination through the activation of the small GTPases RalA and RalB. In this paper, we show that RalB GTPase is upregulated in primary GBM cells. We found that the downregulation of Ral GTPases, mainly RalB, prevents the proliferation of primary GBM cells and triggers a senescence-like response. Moreover, downregulation of RalA and RalB reduces the viability of GBM cells growing as tumorspheres, suggesting a possible role of these GTPases in the survival of GBM stem cells. By using mouse subcutaneous xenografts, we have corroborated the role of RalB in GBM growth in vivo. Finally, we have observed that the knockdown of RalB also inhibits cell growth in temozolomide-resistant GBM cells. Overall, our work shows that GBM cells are especially sensitive to Ral-GTPase availability. Therefore, we propose that the inactivation of Ral-GTPases may be a reliable therapeutic approach to prevent GBM progression and recurrence. 相似文献
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The advent of multicore systems, joined to the potential acceleration of the graphics processing units, has given us a low cost computation capability unprecedented. The new systems alleviate some well-known important architectural problems at the expense of a considerable increment of the programmability wall. Heterogeneity, at both the architectural and programming levels, poses a great challenge to programmers. As a contribution, we propose a development methodology for the automatic source-to-source transformation on specific domains. This methodology is successfully instantiated as a framework to solve Dynamic Programming problems. As a result of applying our framework, the end user (a physicist, a mathematician or a biologist) can express her problem through a latex equation and automatically derive efficient parallel codes for current homogeneous or heterogeneous architectures. The approach allows an easy portability to new emergent architectures. 相似文献