1,721,022 research outputs found

    Chondrosarcoma: New Molecular Insights, Challenges in Near-Patient Preclinical Modeling, and Therapeutic Approaches

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    Chondrosarcoma (CS), the second most common malignant bone tumor after osteosarcoma, accounts for 20-30% of all malignant bone tumors. It mainly affects adults, middle-aged, and elderly people. The CS family includes various entities displaying peculiar biological, genetic, and epigenetic characteristics and clinical behaviors. Conventional CS is the most common subtype. High-grade, dedifferentiated, and mesenchymal CS, as well as unresectable and metastatic CS, exhibit poor prognoses due to their intrinsic resistance to radiotherapy and chemotherapy, underscoring the urgent need for novel therapeutic strategies. CS research is dealing with several challenges. Experimental studies can rely on animal and patient-derived models, but the paucity of representative near-patient preclinical models has hampered predictive drug screening research. This review describes the main clinical and molecular features of CS subtypes, discussing recent data on the genetic alterations and molecular mechanisms involved in CS pathogenesis and progression. The review provides an overview of the current in vitro and in vivo CS models, discusses their advantages and limitations, and highlights the recent efforts in the development of new targeted therapies against CS dependencies, including IDH1/2 mutations, NAD+ dependency, and SIRT1-HIF-2 alpha axis, or exploring DR5 targeting, antiangiogenic therapies, epigenetic drugs, and immunological approaches. All such strategies, in combination with advanced preclinical modeling and personalized multi-omic profiling, hold promise for improving the survival of patients with advanced CS

    Uncoupling of growth inhibition and differentiation in dexamethasonetreated human rhabdomyosarcoma cells

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    The effects of dexamethasone, a synthetic glucocorticoid, and of N, N-dimethylformamide on in vitro growth and differentiation and on proto-oncogene expression of human rhabdomyosarcoma cells were studied. RD/18 clone cells (derived from the embryonal rhabdomyosarcoma cell line RD) treated with 100 nM dexamethasone showed an almost complete block of differentiation: about 5% myosin-positive cells were observed after 2 weeks of culture in dexamethasone-supplemented differentiation medium, compared to 20% of untreated cultures. Dexamethasone also induced a 20-30% growth inhibition and a more flattened morphology. The treatment with N, N-dimethylformamide induced a significantly increased proportion of myosin-positive cells (reaching about 30%) and a 40% growth inhibition. Induction of differentiation inversely correlated with the levels of c-myc proto-oncogene expression: after a 2 week culture dexamethasone-treated cells showed the highest c-myc expression and N, N-dimethylformamide-tre..

    Retrogenic expression of the MET proto-oncogene correlates with the invasive phenotype of human rhabdomyosarcomas

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    The MET oncogene encodes the receptor for HGF/Scatter Factor, known to control cell motility and invasion in epithelial cells, We report that the Met/HGF receptor, absent in differentiated adult skeletal muscles, is aberrantly expressed in clinical samples and in established cell lines of human rhabdomyosarcomas. In both the embryonal and alveolar histotypes the oncogene is overexpressed and, in some cases, amplified, The Met receptor is exposed at the cell surface and is functionally active in response to HGF/Scatter Factor, Accordingly, rhabdomyosarcoma cells exhibit an invasive phenotype in vitro in response to exogenous HGF/Scatter factor, As the factor is known to be produced by connective tissues, a paracrine stimulation of rhabdomyosarcoma invasiveness in vivo is hypothesized, Two alveolar rhabdomyosarcomas were found to co-express the 'two-kringle' alternatively-spliced HGF/Scatter Factor variant, which has been previously shown to stimulate cell motility and matrix invasion in vitro, These cells displayed the invasive phenotype in the absence of exogenous HGF/Scatter Factor, suggesting an autocrine mechanism in vivo, These data indicate that aberrant expression of the MET proto-oncogene provides rhabdomyosarcoma cells with the same property as embryonal myoblasts to migrate into the surrounding connective tissues. RI Lollini, Pier Luigi/A-7644-2008; De Giovanni, Carla/B-1312-200

    The stabilization effect of the triplex vaccine

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    Cancer immunoprevention vaccines are based, like all vaccines, on drugs which gives to the immune system the necessary information to recognize tumor cells as harmful. The vaccine, in endogeneous tumors, cannot eliminate all tumor cells, but maintains them to a non dangerous level. In this paper we show that the vaccine's administrations acts as a stabilizing perturbation for the immune system. Results suggest that it is possible to model such an effect using ODE based technique with an "external input"

    Going Beyond Counting First Authors in Author Co-citation Analysis

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    The 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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