340 research outputs found
Localised and unresectable neuroblastoma in infants: excellent outcome with low-dose primary chemotherapy
Impact-induced melting during accretion of the Earth
Because of the high energies involved, giant impacts that occur during
planetary accretion cause large degrees of melting. The depth of melting in the
target body after each collision determines the pressure and temperature
conditions of metal-silicate equilibration and thus geochemical fractionation
that results from core-mantle differentiation. The accretional collisions
involved in forming the terrestrial planets of the inner Solar System have been
calculated by previous studies using N-body accretion simulations. Here we use
the output from such simulations to determine the volumes of melt produced and
thus the pressure and temperature conditions of metal-silicate equilibration,
after each impact, as Earth-like planets accrete. For these calculations a
parametrised melting model is used that takes impact velocity, impact angle and
the respective masses of the impacting bodies into account. The evolution of
metal-silicate equilibration pressures (as defined by evolving magma ocean
depths) during Earth's accretion depends strongly on the lifetime of
impact-generated magma oceans compared to the time interval between large
impacts. In addition, such results depend on starting parameters in the N-body
simulations, such as the number and initial mass of embryos. Thus, there is the
potential for combining the results, such as those presented here, with
multistage core formation models to better constrain the accretional history of
the Earth
Impact of N-myc amplification on median survival in children with neuroblastoma
Background: Neuroblastoma is the most common extracranial malignant solid tumor
in children under 5 years, and it is characterized by wide clinical and biological heterogeneity.
N-myc oncogene amplification is considered to be one of the most important
prognostic factors used to evaluate survival in these patients.
Objectives: The aim of our study was to determine amplification of the N-myc oncogene
using real-time quantitative polymerase chain reaction (PCR) and to show the influence
of N-myc amplified tumors on the overall survival rate.
Patients and Methods: This study is an analytical historical cohort study of forty children
with neuroblastoma admitted to the Shafa Hospital, Iran from 1999 to 2010. Paraffined
blocks of tumoral tissue were analyzed for N-myc amplification by a PCR. The
degree of N-myc amplification was derived from the ratio of the N-myc oncogene and
the single copy reference gene, NAGK. In the statistical analysis, a Kaplan-Meier survival
analysis was used.
Results: We found a variable degree of N-myc amplification, from 3 to 2 200, in 32 of
the 40 neuroblastomas (80%). NMYC amplification was seen more frequently in patients
older than 2.5 years (71.9%), stage 4 (65.6%) and female (53.1%). Median survival time in the
males was significantly longer than in the females (P = 0.03). The overall median survival
for N-myc amplified tumor patients was 20 months, and 30 months for the non amplified
tumors.
Conclusions: The N-myc amplified tumors may increase the probability of more aggressive
behavior and rapid tumor progression, especially in advanced stages of neuroblastoma.
This study confirmed the importance of obtaining correct measurements of oncogene
amplification in the early evaluation of neuroblastomas in order to target more
aggressive therapies in patients with a higher risk of cancer progression
Synthesis of Alkaline Earth Diazenides MAEN2 (MAE = Ca, Sr, Ba) by Controlled Thermal Decomposition of Azides under High Pressure
The alkaline earth diazenides MAEN2 with MAE = Ca, Sr and Ba were synthesized by a novel synthetic approach, namely, a controlled decomposition of the corresponding azides in a multianvil press at highpressure/ high-temperature conditions. The crystal structure of hitherto unknown calcium diazenide (space group I4/mmm (no. 139), a = 3.5747(6) Å, c = 5.9844(9) Å, Z = 2, wRp = 0.078) was solved and refined on the basis of powder X-ray diffraction data as well as that of SrN2 and BaN2. Accordingly, CaN2 is isotypic with SrN2 (space group I4/mmm (no. 139), a = 3.8054(2) Å, c = 6.8961(4) Å, Z = 2, wRp = 0.057) and the corresponding alkaline earth acetylenides (MAEC2) crystallizing in a tetragonally distorted NaCl structure type. In accordance with literature data, BaN2 adopts a more distorted structure in space group C2/c (no. 15) with a = 7.1608(4) Å, b = 4.3776(3) Å, c = 7.2188(4) Å, β = 104.9679(33)°, Z = 4 and wRp = 0.049). The N−N bond lengths of 1.202(4) Å in CaN2 (SrN2 1.239(4) Å, BaN2 1.23(2) Å) correspond well with a double-bonded dinitrogen unit confirming a diazenide ion [N2]2−. Temperature-dependent in situ powder X-ray diffractometry of the three alkaline earth diazenides resulted in formation of the corresponding subnitrides MAE2N (MAE = Ca, Sr, Ba) at higher temperatures. FTIR spectroscopy revealed a band at about 1380 cm−1 assigned to the N−N stretching vibration of the diazenide unit. Electronic structure calculations support the metallic character of alkaline earth diazenides
Treatment of localised resectable neuroblastoma. Results of the LNESG1 study by the SIOP Europe Neuroblastoma Group
Main objective of this study was to confirm that surgery alone is an effective and safe treatment for localised resectable neuroblastoma except stage 2 with amplified MYCN gene (MYCNA). Of 427 eligible stages 1–2 patients, 411 had normal MYCN and 16 had MYCNA. Of the 288 stage 1 patients with normal MYCN, 1 died of complications and 16 relapsed, 2 of whom died; 5-year relapse-free survival (RFS) and overall survival (OS) rates were 94.3% (95% confidence interval (CI): 91.6–97) and 98.9% (95% CI: 97.7–100), respectively. Of the 123 stage 2 patients with normal MYCN, 1 died of sepsis and 22 relapsed, 8 of whom died (RFS 82.8%, 95% CI: 76.2–89.5; OS 93.2%, 95% CI: 88.7–97.8). In stage 2, OS and RFS were worse for patients with elevated LDH and unfavourable histopathology. Of 16 children with MYCNA, 7 were stage 1 (5 relapses and 4 deaths) and 9 were stage 2 (3 relapses and 2 deaths) patients. In conclusion, surgery alone yielded excellent OS for both stage 1 and 2 neuroblastoma without MYCNA, although stage 2 patients with unfavourable histopathology and elevated LDH suffered a high number of relapses. Both stage 1 and 2 patients with MYCNA were at greater risk of relapse
Detection of GD2-positive cells in bone marrow samples and survival of patients with localised neuroblastoma
The impact of bone marrow (BM) GD2-positive cells on survival has been evaluated in 145 Italian children with localised neuroblastoma (NB) evaluated at diagnosis by anti-GD2 immunocytochemistry. Nineteen of these (13.1%) were found to be BM GD2-positive, with the number of positive cells ranging between 1 and 155 out of 1 × 106 total cells analysed. Seven/19 (38.8%) GD2-positive vs 12/126 (9.5%) GD2-negative patients relapsed. The 5-year event-free survival (EFS) and overall survival of the GD2-positive patients was significantly worse than that of the GD2-negative ones (62.2 vs 89.9%, P<0.001; and 74.9 vs 95.9%, P=0.005, respectively). GD2 positivity was not associated to other known risk factors, and in particular to Myc-N amplification and 1p deletion. Among Myc-N-negative patients, the EFS of those negative for both GD2 and 1p deletion was significantly better than in children positive for either one of these two markers (EFS=96.9 vs 66.0%, P<0.001). In conclusion, GD2 positivity may represent a prognostic marker for patients with non-metastatic NB without Myc-N amplification, and its combination with genetic alterations might help identifying patients that require a more careful follow-up
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