1,720,991 research outputs found
New instruments in molecular genetics for the prevention of X chromosome-linked muscular dystrophy
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The Emerging Roles of Extracellular Vesicles in Osteosarcoma
Full text linkExtracellular vesicles (EVs) are heterogeneous nanosized vesicles that are constitutively released by virtually all types of cells. They have been isolated in almost all body fluids. EVs cargo consists of various molecules (nucleic acids, proteins, lipids, and metabolites), that can be found on EVs surface and/or in their lumen. EVs structure confer stability and allow the transfer of their cargo to specific cell types over a distance. EVs play a critical role in intercellular communication in physiological and pathological settings. The broadening of knowledge on EVs improved our comprehension of cancer biology as far as tumor development, growth, metastasis, chemoresistance, and treatment are concerned. Increasing evidences suggest that EVs have a significant role in osteosarcoma (OS) development, progression, and metastatic process. The modulation of inflammatory communication pathways by EVs plays a critical role in OS and in other bone-related pathological conditions such as osteoarthritis and rheumatoid arthritis. In this review we describe the emerging data on the role of extracellular vesicles in osteosarcoma and discuss the effects and function of OS-derived EVs focusing on their future applicability in clinical practice
Involvement of HIF-1α activation in the doxorubicin resistance of human osteosarcoma cells.
No full textOsteosarcoma is the most common primary bone cancer in children and adolescents. Despite aggressive treatment regimens, survival outcomes remain unsatisfactory, particularly in patients with metastatic and/or recurrent disease. Unfortunately, treatment failure is commonly due to the development of chemoresistance, for which the underlying molecular mechanisms remain unclear. The aim of the present study was to investigate the role of hypoxia-inducible factor 1α (HIF‐1α) and its signalling pathways as mediators of drug-resistance in human osteosarcoma. Toward this aim, we established two osteosarcoma cell lines selected for resistance to doxorubicin, a drug of choice in the treatment of this tumour. Our results showed that the multidrug resistance (MDR) phenotype was also mediated by HIF-1α, the most important regulator of cell adaptation to hypoxia. Our data showed that this transcription factor promoted the outward transport of intracellular doxorubicin by activating the P-glycoprotein (P-gp) expression in osteosarcoma cells maintained in normoxic conditions. In addition, it hindered doxorubicin-induced apoptosis by regulating the expression of c-Myc and p21. Finally, we observed that the doxorubicin-resistant cells maintained for 2 months of continuous culture in a drug-free medium, lost their drug-resistance and this effect was associated with the absence of HIF-1α expression. The emerging role of HIF-1α in osteosarcoma biology indicates its use as a valuable therapeutic target
Origin of new mutations in Duchenne muscular dystrophy
No full textNine unrelated pedigrees in which Duchenne muscular dystrophy (DMD) was not present in more than one sibship were studied, using 6 DNA polymorphisms closely linked to the DMD gene. The reconstruction of grandparental haplotypes indicates the occurrence of at least three new mutations, two in grandpaternal chromosomes and one in a grandmaternal chromosome. Two additional (but less well documented) new mutations might have occurred respectively in a grandfather's and in a grandmother's chromosome, the latter being represented by a deletion mutation. The new mutations detected in this study therefore add to a total of either three or five out of nine apparently independent mutations present in pedigrees without recurrence of the disorder
Extracellular nanovesicles secreted by human osteosarcoma cells promote angiogenesis
Full text linkAngiogenesis involves a number of different players among which extracellular nanovesicles (EVs) have recently been proposed as an efficient cargo of pro-angiogenic mediators. Angiogenesis plays a key role in osteosarcoma (OS) development and progression. Acidity is a hallmark of malignancy in a variety of cancers, including sarcomas, as a result of an increased energetic metabolism. The aim of this study was to investigate the role of EVs derived from osteosarcoma cells on angiogenesis and whether extracellular acidity, generated by tumor metabolism, could influence EVs activity. For this purpose, we purified and characterized EVs from OS cells maintained at either acidic or neutral pH. The ability of EVs to induce angiogenesis was assessed in vitro by endothelial cell tube formation and in vivo using chicken chorioallantoic membrane. Our findings demonstrated that EVs derived from osteosarcoma cells maintained either in acidic or neutral conditions induced angiogenesis. The results showed that miRNA and protein content of EVs cargo are correlated with pro-angiogenic activity and this activity is increased by the acidity of tumor microenvironment. This study provides evidence that EVs released by human osteosarcoma cells act as carriers of active angiogenic stimuli that are able to promote endothelial cell functions relevant to angiogenesis
Effect of tulipin on cell cycle progression analyzed by BrdUrd incorporation.
No full textThe effect of tulipin, a protein from plant origin recently purified, on cell
cycle progression has been analyzed in the sensitive EUE cells by BrdUrd
incorporation. The cytofluorimetric results demonstrate that tulipin specifically
interacts with the S phase, with a dose-dependent decrease of the total S phase
cells and an increase of the G1/G2 cells after 4 h of treatment in the
synchronized EUE cells, whereas in the asynchronous population it mainly causes a
dose-dependent decrease in the incorporation of BrdUrd per cell
Multimodal transfer of MDR by exosomes in human osteosarcoma
No full textExosomes are extracellular vesicles released by both normal and tumour cells which are involved in a new intercellular communication pathway by delivering cargo (e.g., proteins, microRNAs, mRNAs) to recipient cells. Tumour-derived exosomes have been shown to play critical roles in different stages of tumour growth and progression. In this study, we investigated the potential role of exosomes to transfer the multidrug resistance (MDR) phenotype in human osteosarcoma cells. Exosomes were isolated by differential centrifugation of culture media from multidrug resistant human osteosarcoma MG-63DXR30 (Exo/DXR) and MG-63 parental cells (Exo/S). Exosome purity was examined by transmission electron microscopy and confirmed by immunoblot analysis for the expression of specific exosomal markers. Our data showed that exosomes derived from doxorubicin-resistant osteosarcoma cells could be taken up into secondary cells and induce a doxorubicin-resistant phenotype. The incubation of osteosarcoma cells with Exo/DXR decreased the sensitivity of parental cells to doxorubicin, while exposure with Exo/S was ineffective. In addition, we demonstrated that Exo/DXR expressed higher levels of MDR-1 mRNA and P-glycoprotein compared to Exo/S (p=0.03). Interestingly, both MDR-1 mRNA and P-gp increased in MG-63 cells after incubation with Exo/DXR, suggesting this as the main mechanism of exosome-mediated transfer of drug resistance. Our findings suggest that multidrug resistant osteosarcoma cells are able to spread their ability to resist the effects of doxorubicin treatment on sensitive cells by transferring exosomes carrying MDR-1 mRNA and its product P-glycoprotein
Mapping of the Emery-Dreifuss gene through reconstruction of crossover points in two Italian pedigrees
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Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
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