ORCID Profile
0000-0002-2986-4254
Current Organisations
UCSF Medical Center
,
San Francisco General Hospital (now Zuckerberg San Francisco General Hospital)
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Publisher: Proceedings of the National Academy of Sciences
Date: 16-08-2004
Abstract: The mechanisms causing persistence of embryonal cells that later give rise to tumors is unknown. One tumorigenic factor in the embryonal childhood tumor neuroblastoma is the MYCN protooncogene. Here we show that normal mice developed neuroblast hyperplasia in paravertebral ganglia at birth that completely regressed by 2 weeks of age. In contrast, ganglia from MYCN transgenic ( TH-MYCN ) mice demonstrated a marked increase in neuroblast hyperplasia and MycN expression during week 1. Regression of neuroblast hyperplasia was then delayed and incomplete before neuroblastoma tumor formation at 6 and 13 weeks in homo- and hemizygote mice, respectively. Paravertebral neuronal cells cultured from perinatal TH-MYCN mice exhibited 3- to 10-fold resistance to nerve growth factor (NGF) withdrawal, compared with normal mice. Both low- and high-affinity NGF receptors were expressed in perinatal neuroblast hyperplasia but not in neuroblastoma tumor tissue. MYCN transgene lification was present at low levels in perinatal neuroblast hyperplasia from both homo- and hemizygote TH-MYCN mice. However, only in hemizygous mice did tumor formation correlate with a stepwise increase in the frequency of MYCN lification. These data suggest that inappropriate perinatal MycN expression in paravertebral ganglia cells from TH-MYCN mice initiated tumorigenesis by altering the physiologic process of neural crest cell deletion. Persisting embryonal neural crest cells underwent further changes, such as MYCN lification and repression of NGF receptor expression, during tumor progression. Our studies provide a model for studying perinatal factors influencing embryonal tumor initiation.
Publisher: AIP Publishing
Date: 11-09-2014
DOI: 10.1063/1.4895113
Abstract: Use of symmetry can dramatically reduce the computational cost (running time and memory allocation) of self-consistent-field ab initio calculations for molecular and crystalline systems. Crucial for running time is symmetry exploitation in the evaluation of one- and two-electron integrals, diagonalization of the Fock matrix at selected points in reciprocal space, reconstruction of the density matrix. As regards memory allocation, full square matrices (overlap, Fock, and density) in the Atomic Orbital (AO) basis are avoided and a direct transformation from the packed AO to the symmetry adapted crystalline orbital basis is performed, so that the largest matrix to be handled has the size of the largest sub-block in the latter basis. Quantitative ex les, referring to the implementation in the CRYSTAL code, are given for high symmetry families of compounds such as carbon fullerenes and nanotubes.
Publisher: Springer Science and Business Media LLC
Date: 26-09-2010
DOI: 10.1038/NM.2227
Publisher: Springer Science and Business Media LLC
Date: 22-11-2013
Publisher: Royal Society of Chemistry (RSC)
Date: 2015
DOI: 10.1039/C5CP01537E
Abstract: Accurate ab initio calculations of thermodynamic and structural thermal properties of corundum demonstrate its quasi-harmonic nature up to the melting temperature.
Publisher: AIP Publishing
Date: 28-05-2015
DOI: 10.1063/1.4921781
Abstract: We report accurate ab initio theoretical predictions of the elastic, seismic, and structural anisotropy of the orthorhombic Mg2SiO4 forsterite crystal at high pressures (up to 20 GPa) and temperatures (up to its melting point, 2163 K), which constitute earth’s upper mantle conditions. Single-crystal elastic stiffness constants are evaluated up to 20 GPa and their first- and second-order pressure derivatives reported. Christoffel’s equation is solved at several pressures: directional seismic wave velocities and related properties (azimuthal and polarization seismic anisotropies) discussed. Thermal structural and average elastic properties, as computed within the quasi-harmonic approximation of the lattice potential, are predicted at high pressures and temperatures: directional thermal expansion coefficients, first- and second-order pressure derivatives of the isothermal bulk modulus, and P-V-T equation-of-state. The effect on computed properties of five different functionals, belonging to three different classes of approximations, of the density functional theory is explicitly investigated.
Publisher: Informa UK Limited
Date: 04-2012
DOI: 10.4161/AUTO.19496
Publisher: Wiley
Date: 11-03-2014
DOI: 10.1002/QUA.24658
Publisher: AIP Publishing
Date: 04-01-2013
DOI: 10.1063/1.4772960
Abstract: The vibrational properties of CaCO3 aragonite have been investigated both theoretically, by using a quantum mechanical approach (all electron Gaussian type basis set and B3LYP HF-DFT hybrid functional, as implemented in the CRYSTAL code) and experimentally, by collecting polarized infrared (IR) reflectance and Raman spectra. The combined use of theory and experiment permits on the one hand to analyze the many subtle features of the measured spectra, on the other hand to evidentiate limits and deficiencies of both approaches. The full set of TO and LO IR active modes, their intensities, the dielectric tensor (in its static and high frequency components), and the optical indices have been determined, as well as the Raman frequencies. Tools such as isotopic substitution and graphical animation of the modes are available, that complement the analysis of the spectrum.
Publisher: Wiley
Date: 2000
DOI: 10.1002/1096-911X(20001201)35:6<585::AID-MPO20>3.0.CO;2-P
Abstract: Although the association between N-myc gene lification and poor clinical outcome in neuroblastoma is well established, the mechanism by which lification influences prognosis is not well defined. We used a human N-myc transgenic mouse model to investigate the role of N-myc in neuroblastoma, including its relationship to the multidrug-resistance-associated protein (MRP) gene. We developed a rapid real-time PCR method to distinguish homozygous and hemizygous N-myc mice that is comparable to Southern analysis. A highly significant correlation (P < 0.0001) between N-myc and MRP expression was demonstrated in murine tumors. Amplification of the transgene was observed in the majority of tumors, highlighting the clinical relevance of this model. However, no correlation between N-myc expression and transgene dosage or tumor latency was observed. The data suggest that increased N-myc dosage contributes to increased tumor incidence and decreased latency by mechanisms independent of N-myc expression.
Publisher: Oxford University Press (OUP)
Date: 16-09-2003
DOI: 10.1093/JNCI/DJG045
Abstract: Human MYCN (hMYCN) oncogene lification is a powerful predictor of treatment failure in childhood neuroblastoma, and dysregulation of hMYCN protein expression appears to be critically involved in the pathogenesis of this disease. We used hMYCN antisense (AS) oligonucleotides to investigate, both in vitro and in vivo, the therapeutic potential of inhibiting hMYCN expression. We transiently transfected human neuroblastoma IMR-32 cells, which have an lified hMYCN gene, with fluorescently labeled hMYCN AS or scrambled (SCR) control oligonucleotides and used fluorescence-activated cell sorting to enrich for cell populations containing different levels of the oligonucleotides. We used fluorescence immunocytochemistry or reverse transcription polymerase chain reaction to assay gene expression levels and trypan blue exclusion to assay growth inhibition in the cell populations. We examined the effects of continuous treatment for 6 weeks with AS or SCR oligonucleotides via subcutaneously implanted microosmotic pumps on tumor growth in a transgenic mouse model of hMYCN-induced neuroblastoma (n = 20 mice per group). All statistical tests were two-sided. IMR-32 cells treated with AS oligonucleotides had approximately half as much hMYCN protein and cell proliferation as either SCR oligonucleotide-transfected or mock-transfected controls the differences were statistically significant. Transgenic mice treated with AS oligonucleotides had lower tumor incidence and statistically significantly lower tumor mass than SCR-treated or untreated control mice. Compared with control treatments, AS oligonucleotide treatment in vitro and in vivo was associated with decreased expression of hMYCN and putative hMYCN target genes but not with that of closely related genes. Several AS oligonucleotide-treated mice developed tumors contralateral to the site of oligonucleotide administration, whereas SCR oligonucleotide-treated or untreated mice displayed bilateral tumor growth. Decreased expression of hMYCN protein is achievable with the use of AS oligonucleotide treatment, even in the presence of hMYCN oncogene lification. Antisense strategies targeting the hMYCN oncogene in vivo decrease mouse neuroblastoma tumorigenesis. Investigation of their clinical effect in children with neuroblastoma is warranted.
Location: United States of America
Location: United States of America
Location: United States of America
No related grants have been discovered for Alessandro Erba.