1,720,970 research outputs found
A murine model for virotherapy of malignant brain tumors.
No full textGlioblastomas (GBMs) are very aggressive and almost incurable brain tumors. The development of new therapeutical approaches capable of selectively killing cancer cells could represent a step forward to fight cancer. With this aim we tested the efficacy of a novel oncolytic therapy based on recombinant herpes simplex viruses (HSVs) infecting exclusively cells expressing the human receptor HER-2 [1, 2], overexpressed in about 15% of GBMs [3]. For this study we exploited a murine GBM model based on PDGF-B embryonic transduction [4, 5]. We engineered cell cultures derived from this model to express HER-2 and we injected intracranically such cultures in NOD/SCID mice. We evaluated the efficacy of R-LM113, a recombinant HSV directed to HER-2, in this glioma model expressing HER-2. We demonstrated that mice injected with engineered glioma cells infected with R-LM113 developed gliomas with a statistically significant delay compared to mice injected with non-infected engineered glioma cells
Serotonin via 5HT2B-mediated signalling acts as a neurotrophic factor during Xenopus eye morphogenesis
No full textSerotonin 2B receptor signaling is required for craniofacial and ocular morphogenesis in Xenopus
No full textSerotonin 2B receptor signaling is required for craniofacial morphogenesis and jaw joint formation in Xenopus
No full textSerotonin (5-HT) is a neuromodulator that plays many different roles in adult and embryonic life. Among the 5-HT receptors, 5-
HT2B is one of the key mediators of 5-HT functions during development. We used Xenopus laevis as a model system to further
investigate the role of 5-HT2B in embryogenesis, focusing on craniofacial development. By means of gene gain- and loss-offunction
approaches and tissue transplantation assays, we demonstrated that 5-HT2B modulates, in a cell-autonomous manner,
postmigratory skeletogenic cranial neural crest cell (NCC) behavior without altering early steps of cranial NCC development and
migration. 5-HT2B overexpression induced the formation of an ectopic visceral skeletal element and altered the dorsoventral
patterning of the branchial arches. Loss-of-function experiments revealed that 5-HT2B signaling is necessary for jaw joint
formation and for shaping the mandibular arch skeletal elements. In particular, 5-HT2B signaling is required to define and sustain
the Xbap expression necessary for jaw joint formation. To shed light on the molecular identity of the transduction pathway
acting downstream of 5-HT2B, we analyzed the function of phospholipase C beta 3 (PLC) in Xenopus development and showed
that PLC is the effector of 5-HT2B during craniofacial development. Our results unveiled an unsuspected role of 5-HT2B in
craniofacial development and contribute to our understanding of the interactive network of patterning signals that is involved in
the development and evolution of the vertebrate mandibular arch
5-HT2B mediated signaling partecipates in retinal and craniofacial morphogenesis during Xenopus laevis developmen
No full textEfficacy of HER2 retargeted herpes simplex virus as therapy for high-grade glioma in immunocompetent mice.
No full textReplication-competent oncolytic herpes simplex viruses (HSVs) are considered a promising therapeutic approach for treatment of high-grade gliomas (HGGs), which are usually resistant to all the available treatments. We previously demonstrated that R-LM113, a recombinant HSV-1 fully retargeted to the human epidermal growth factor receptor 2 (HER2), is safe and prolongs survival of immunodeficient NOD/SCID mice in an intracranial model of HGG. However, because the treatment is designed to be employed on immunocompetent patients, it is necessary to test whether the host immune system impairs the viral efficacy or triggers a potentially fatal reaction. Here we confirmed the safety of R-LM113 in the immunocompetent mouse strain BALB/c, where it does not trigger encephalitis when intracranially inoculated. Then, we set up a syngeneic HGG model expressing HER2 in adult BALB/c mice and evaluated R-LM113 therapeutic efficacy. We found that R-LM113 leads to a significant improvement in animal survival when administered at the time of tumor inoculation, as well as when injected into an already established tumor. This study suggests that the host immune defenses do not curtail the oncolytic antitumor activity of replication-competent HSV R-LM113, which results effective in counteracting tumor growth
Overexpression of 5-HT2B receptor results in retinal dysplasia and defective ocular morphogenesis in Xenopus embryos
No full textIn vertebrates, eye development comprises inductive and morphogenetic events that are finely regulated by the coordinated action of many intrinsic and extrinsic factors. Recent evidence suggested that neurotransmitters could be enumerated by the extracellular signals contributing to the retinal and eye development. We showed that, among these neuromodulators, serotonin acting via the 5-HT2B receptor, is involved in the control of retinoblasts proliferation and survival in Xenopus embryogenesis. To further clarify the role of 5-HT2B receptor in ocular development, we performed a gene gain of function analysis in vitro and in vivo in Xenopus embryos. We confirmed that 5-HT2B overexpression is per se sufficient to promote cell proliferation in a neuroblastoma cell line. The in vivo experiments revealed that an over serotonin signaling, via 5-HT2B receptors, resulted in the formation of eyes with an irregular form, position and orientation. Interestingly, we showed 5-HT2B gene expression in periocular mesenchyme that represents a key signaling center required for a correct eye morphogenesis. Moreover, the 5-HT2B receptor overexpressing retina, displays a disorganization of the typical laminar structure with the presence of retinal cells scattered in ectopic positions or forming rosette like structures. On the whole our data support the idea that serotonin signalling has to be finely regulated during eye development to allow a correct retinogenesis and may participate in the correct orchestration and synergism of all the factors and events that regulate eye morphogenesis in ocular and periocular tissues
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
- …
