A5046258647- CAR-T cell therapy research
- Neurogenesis and neuroplasticity mechanisms
- Epigenetics and DNA Methylation
- Genetics and Neurodevelopmental Disorders
- Hedgehog Signaling Pathway Studies
- Cancer-related gene regulation
- Pluripotent Stem Cells Research
- Developmental Biology and Gene Regulation
- Axon Guidance and Neuronal Signaling
- Chemokine receptors and signaling
- interferon and immune responses
- Glioma Diagnosis and Treatment
- MicroRNA in disease regulation
- Virus-based gene therapy research
- Signaling Pathways in Disease
- Neuroblastoma Research and Treatments
- Cancer-related Molecular Pathways
- Muscle Physiology and Disorders
- Kruppel-like factors research
- Transcranial Magnetic Stimulation Studies
- S100 Proteins and Annexins
- Prostate Cancer Diagnosis and Treatment
- Bladder and Urothelial Cancer Treatments
- Nanowire Synthesis and Applications
- Chromatin Remodeling and Cancer
Bambino Gesù Children's Hospital
2023-2024
National Research Council
2012-2024
Institute of Cell Biology and Neurobiology
2012-2023
Collaborative Group (United States)
2023
Start Treatment & Recovery Centers
2023
Fondazione Santa Lucia
2012-2018
National Academies of Sciences, Engineering, and Medicine
2012-2015
National Agency for New Technologies, Energy and Sustainable Economic Development
2010
Piedmont Reference Center for Epidemiology and Cancer Prevention
2007
Abstract Chimeric antigen receptor T (CAR-T) cell therapy may achieve long-lasting remission in patients with B-cell malignancies not responding to conventional therapies. However, potentially severe and hard-to-manage side effects, including cytokine release syndrome (CRS), neurotoxicity macrophage activation syndrome, the lack of pathophysiological experimental models limit applicability development this form therapy. Here we present a comprehensive humanized mouse model, by which show...
Abstract Purpose: Medulloblastoma (MB), the most common childhood malignant brain tumor, has a poor prognosis in about 30% of patients. The current standard care, which includes surgery, radiation, and chemotherapy, is often responsible for cognitive, neurologic, endocrine side effects. We investigated whether chimeric antigen receptor (CAR) T cells directed toward disialoganglioside GD2 can represent potentially more effective treatment with reduced long-term Experimental Design: expression...
Abstract Physical exercise increases the generation of new neurons in adult neurogenesis. However, only few studies have investigated beneficial effects physical paradigms impaired Here, we demonstrate that running fully reverses deficient neurogenesis within hippocampus and subventricular zone lateral ventricle, observed mice lacking antiproliferative gene Btg1. We also evaluated for first time how influences cell cycle kinetics stem precursor subpopulations wild-type Btg1-null mice, using...
Btg1 belongs to a family of cell cycle inhibitory genes. We observed that is highly expressed in adult neurogenic niches, i.e., the dentate gyrus and subventricular zone (SVZ). Thus, we generated knockout mice analyze role process generation new neurons. Ablation causes transient increase proliferating stem progenitor cells at post-natal day 7; however, 2 months age number these cells, as well mature neurons, greatly decreases compared wild-type controls. Remarkably, Btg1-null exit after...
A failure in the control of proliferation cerebellar granule neuron precursor cells (GCPs), located external granular layer (EGL) cerebellum, gives rise to medulloblastoma. To investigate process neoplastic transformation GCPs, we generated a new medulloblastoma model by crossing Patched1 heterozygous mice, which develop medulloblastomas with low frequency, mice lacking Tis21 gene. Overexpression is known inhibit and trigger differentiation GCPs; its expression decreases human...
In the neurogenic niches-the dentate gyrus of hippocampus and subventricular zone (SVZ) adjacent to lateral ventricles-stem cells continue divide during adulthood, generating progenitor new neurons, self-renew, thus maintaining stem cell pool. During aging, numbers stem/progenitor in niches are reduced. The preservation pool is committed a number antiproliferative genes, with role quiescence neural cells. cyclin-dependent kinase inhibitor p16Ink4a, whose expression increases age, controls...
The dentate gyrus of the hippocampus is one two brain areas generating throughout life new neurons, which contribute to formation episodic/associative memories. During aging, production neurons decreases and a cognitive decline occurs. Dietary factors influence neuronal function synaptic plasticity; among them phenolic compound hydroxytyrosol (HTyr), present in olive oil, displays neuroprotective effects. As age impacts primarily on hippocampus-dependent processes, we wondered whether HTyr...
Within the hippocampal circuitry, basic function of dentate gyrus is to transform memory input coming from enthorinal cortex into sparse and categorized outputs CA3, in this way separating related information. New neurons generated during adulthood appear facilitate process, allowing a better separation between closely spaced memories (pattern separation). The evidence underlying model has been gathered essentially by ablating newly adult-generated neurons. This approach, however, does not...
Bone Morphogenic Proteins (BMPs) and the Notch pathway regulate quiescence self-renewal of stem cells subventricular zone (SVZ), an adult neurogenic niche. Here we analyze role at intersection these pathways Tis21 (Btg2), a gene regulating proliferation differentiation SVZ progenitor cells.In Tis21-null cultured neurospheres, observed strong decrease in expression BMP4 its effectors Smad1/8, while antineural mediators Hes1/5 bHLH inhibitors Id1-3 increased. Consistently, proneural NeuroD1...
The dentate gyrus of the hippocampus and subventricular zone are neurogenic niches where neural stem progenitor cells replicate throughout life to generate new neurons. Btg1 gene maintains in quiescence. deletion leads an early transient increase stem/progenitor division, followed, however, by a decrease during adulthood their proliferative capability, accompanied apoptosis. Since physiological neurogenesis occurs aging, knockout mouse may represent model aging. We have previously observed...
Cell proliferation and differentiation are interdependent processes. Here, we have asked to what extent the two processes of neural progenitor cell amplification functionally separated. Thus, analyzed whether it is possible rescue a defect terminal in cells dentate gyrus, where new neurons generated throughout life, by inducing their and/or with different stimuli appropriately timed. As model used Tis21 knockout mouse, whose gyrus neurons, as demonstrated us others, an intrinsic...
Abstract Medulloblastoma (MB) is the most common pediatric tumor of CNS, representing ∼20% all childhood CNS tumors. Although in recent years many molecular mechanisms that control MB development have been clarified, effects biological factors such as sex on this remain to be explained. Epidemiological data, fact, indicate a significant difference incidence between 2 sexes, with considerably higher susceptibility males than females. Besides different susceptibility, female also favorable...
Medulloblastoma (MB), the tumor of cerebellum, is most frequent brain cancer in childhood and a major cause pediatric mortality. Based on gene profiling, four MB subgroups have been identified, i.e., Wnt or Sonic Hedgehog (Shh) types, subgroup 3 4. The Shh-type has shown to arise from cerebellar precursors granule neurons (GCPs), where hyperactivation Shh pathway leads their neoplastic transformation. We previously that Tis21 (PC3/Btg2) inhibits proliferation promotes differentiation...
Medulloblastoma (MB), tumor of the cerebellum, remains a leading cause cancer-related mortality in childhood. We previously showed, mouse model spontaneous MB (Ptch1+/-/Tis21-/-), that defect migration cerebellar granule neuron precursor cells (GCPs) correlates with an increased frequency MB. This occurs because GCPs, rather than migrating internally and differentiating, remain longer proliferative area at surface, becoming targets transforming insults. Furthermore, we identified chemokine...
GENERAL COMMENTARY article Front. Neurosci., 24 January 2013Sec. Neurogenesis https://doi.org/10.3389/fnins.2012.00198
We have previously generated a mouse model ( Ptch1 +/− /Tis21 KO ), which displays high frequency spontaneous medulloblastoma, pediatric tumor of the cerebellum. Early postnatal cerebellar granule cell precursors (GCPs) this show, in consequence deletion Tis21 , defect Cxcl3-dependent migration. asked whether migration defect, forces GCPs to remain proliferative area at surface, would be only inducer their transformation. In report we by further bioinformatic analysis our microarray data...
We have recently generated a novel medulloblastoma (MB) mouse model with activation of the Shh pathway and lacking MB suppressor Tis21 (Patched1+/-/Tis21KO). Its main phenotype is defect migration cerebellar granule precursor cells (GCPs). By genomic analysis GCPs in vivo, we identified as drug target major responsible this down-regulation promigratory chemokine Cxcl3. Consequently, remain longer cerebellum proliferative area, frequency enhanced. Here, further analyzed genes deregulated...
Although active surveillance for patients with low-risk prostate cancer (LRPC) has been recommended years, its adoption at the population level is often limited.To make available LRPC using a research framework and to compare patient characteristics clinical outcomes between those who receive vs radical treatments diagnosis.This population-based, prospective cohort study was designed by large multidisciplinary group of specialists patients' representatives. The conducted within all 18...
About 30% of medulloblastomas (MBs), a tumor the cerebellum, arise from cerebellar granule cell precursors (GCPs) undergoing transformation following activation Sonic hedgehog (Shh) pathway. To study this process, we generated new MB model by crossing Patched1 heterozygous (Ptch1 +/-) mice, which develop spontaneous Shh-type MBs, with mice lacking B-cell translocation gene 1 (Btg1), regulator development. In MBs developing in Ptch1 +/- deletion Btg1 does not alter and lesion frequencies, nor...