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Rhabdomyosarcoma (RMS) is the most frequent soft tissue sarcoma (STS) in children and adolescents. In Spain the annual incidence is 4.4 cases per million children < 14 years. It is an uncommon neoplasm in adults, but 40% of RMS are diagnosed in patients over 20 years of age, representing 1% of all STS in this age group. RMS can appear anywhere in the body, with some sites more frequently affected including head and neck, genitourinary system and limbs. Assessment of a patient with suspicion of RMS includes imaging studies (MRI, CT, PET-CT) and biopsy. All patients with RMS should receive chemotherapy, either at diagnosis in advanced or metastatic stages, or after initial resection in early local stages. Local control includes surgery and/or radiotherapy depending on site, stage, histology and response to chemotherapy. This guide provides recommendations for diagnosis, staging and treatment of this neoplasm. [ABSTRACT FROM AUTHOR]

Purpose: Early phase trials are crucial in developing innovative effective agents for childhood malignancies. We report the activity in early phase paediatric oncology trials in Spain from its beginning to the present time and incorporate longitudinal data to evaluate the trends in trial characteristics and recruitment rates. Methods: Members of SEHOP were contacted to obtain information about the open trials at their institutions. The study period was split into two equal periods for analysis: 2007–2013 and 2014–2020. Results: Eighty-one trials and two molecular platforms have been initiated. The number of trials has increased over the time of the study for all tumour types, with a predominance of trials available for solid tumours (66%). The number of trials addressed to tumours harbouring specific molecular alterations has doubled during the second period. The proportion of industry-sponsored compared to academic trials has increased over the same years. A total of 565 children and adolescents were included, with an increasing trend over the study period. For international trials, the median time between the first country study approval and the Spanish competent authority approval was 2 months (IQR 0–6.5). Fourteen out of 81 trials were sponsored by Spanish academic institutions. Conclusions: The number of available trials, and the number of participating patients, has increased in Spain from 2007. Studies focused on molecular-specific targets are now being implemented. Barriers to accessing new drugs for all ranges of age and cancer diseases remain. Additionally, opportunities to improve academic research are still required in Spain. [ABSTRACT FROM AUTHOR]

The magnetic properties of SrFe 12 O 19 , a paradigmatic hexaferrite for permanent magnet applications, have been addressed in detail combining density functional theory including spin–orbit coupling and a Hubbard U term with Monte Carlo simulations. This multiscale approach allows to estimate the Néel temperature of the material from ab initio exchange constants, and to determine the influence of different computational conditions on the magnetic properties by direct comparison versus available experimental data. It is found that the dominant influence arises from the choice of the Hubbard U term, with a value in the 2–3 eV range as the most adequate to quantitatively reproduce the two most relevant magnetic properties of this material, namely: its large perpendicular magnetocrystalline anisotropy and its elevated Néel temperature. [ABSTRACT FROM AUTHOR]

Introduction: Cancer and blood disorders in children are rare. The progressive improvement in survival over the last decades largely relies on the development of international academic clinical trials that gather the sufficient number of patients globally to elaborate solid conclusions and drive changes in clinical practice. The participation of Spain into large international academic trials has traditionally lagged behind of other European countries, mainly due to the burden of administrative tasks to open new studies, lack of financial support and limited research infrastructure in our hospitals. Methods: The objective of ECLIM-SEHOP platform (Ensayos Clínicos Internacionales Multicéntricos-SEHOP) is to overcome these difficulties and position Spain among the European countries leading the advances in cancer and blood disorders, facilitate the access of our patients to novel diagnostic and therapeutic approaches and, most importantly, continue to improve survival and reducing long-term sequelae. ECLIM-SEHOP provides to the Spanish clinical investigators with the necessary infrastructural support to open and implement academic clinical trials and registries. Results: In less than 3 years from its inception, the platform has provided support to 20 clinical trials and 8 observational studies, including 8 trials and 4 observational studies where the platform performs all trial-related tasks (integral support: trial setup, monitoring, etc.) with more than 150 patients recruited since 2017 to these studies. In this manuscript, we provide baseline metrics for academic clinical trial performance that permit future comparisons. Conclusions: ECLIM-SEHOP facilitates Spanish children and adolescents diagnosed with cancer and blood disorders to access state-of-the-art diagnostic and therapeutic strategies. [ABSTRACT FROM AUTHOR]

Background: Rhabdomyosarcoma (RMS) is the most common type of soft tissue sarcoma in children. The Hedgehog (HH) pathway is known to develop an oncogenic role in RMS. However, the molecular mechanism that drives activation of the pathway in RMS is not well understood.Methods: The expression of HH ligands was studied by qPCR, western blot and immunohistochemistry. Functional and animal model studies were carried out with cells transduced with shRNAs against HH ligands or treated with HH-specific inhibitors (Vismodegib and MEDI-5304). Finally, the molecular characterisation of an off-target effect of Vismodegib was also made.Results: The results showed a prominent expression of HH ligands supporting an autocrine ligand-dependent activation of the pathway. A comparison of pharmacologic Smoothened inhibition (Vismodegib) and HH ligand blocking (MEDI-5304) is also provided. Interestingly, a first description of pernicious off-target effect of Vismodegib is also reported.Conclusions: The clarification of the HH pathway activation mechanism in RMS opens a door for targeted therapies against HH ligands as a possible alternative in the future development of better treatment protocols. Moreover, the description of a pernicious off-target effect of Vismodegib, via unfolded protein response activation, may mechanistically explain its previously reported inefficiency in several ligand-dependent cancers. [ABSTRACT FROM AUTHOR]

The use of preclinical models is essential in translational cancer research and especially important in pediatric cancer given the low incidence of each particular type of cancer. Cell line cultures have led to significant advances in cancer biology. However, cell lines have adapted to growth in artificial culture conditions, thereby undergoing genetic and phenotypic changes which may hinder the translational application. Tumor grafts developed in mice from patient tumor tissues, generally known as patient-derived xenografts (PDXs), are interesting alternative approaches to reproducing the biology of the original tumor. This review is focused on highlighting the interest of PDX models in pediatric cancer research and supporting strategies of personalized medicine. This review provides: (1) a description of the background of PDX in cancer, (2) the particular case of PDX in pediatric cancer, (3) how PDX can improve personalized medicine strategies, (4) new methods to increase engraftment, and, finally, (5) concluding remarks. [ABSTRACT FROM AUTHOR]

Background: Rhabdomyosarcoma (RMS) is the commonest type of soft-tissue sarcoma in children. Patients with metastatic RMS continue to have very poor prognosis. Recently, several works have demonstrated a connection between Notch pathway activation and the regulation of cell motility and invasiveness. However, the molecular mechanisms of this possible relationship remain unclear.Methods: The Notch pathway was manipulated pharmacologically and genetically. The mRNA changes were analysed by quantitative PCR and protein variations by western blot and immunofluorescence. Finally, the capabilities of RMS cells to adhere, heal a wound and invade were assessed in the presence of neuronal cadherin (N-cadherin)- and α9-integrin-blocking antibodies.Results: Cells treated with γ-secretase inhibitor showed lower adhesion capability and downregulation of N-cadherin and α9-integrin. Genetic manipulation of the Notch pathway led to concomitant variations in N-cadherin and α9-integrin. Treatment with anti-N-cadherin-blocking antibody rendered marked inhibition of cell adhesion and motility, while anti-α9-integrin-blocking antibody exerted a remarkable effect on cell adhesion and invasiveness.Conclusion: Neuronal cadherin and α9-integrin are postulated as leading actors in the association between the Notch pathway and promotion of cell adhesion, motility and invasion, pointing to these proteins and the Notch pathway itself as interesting putative targets for new molecular therapies against metastases in RMS. [ABSTRACT FROM AUTHOR]

Purpose: Despite numerous advances, survival remains dismal for children and adolescents with poor prognosis cancers or those who relapse or are refractory to first line treatment. There is, therefore, a major unmet need for new drugs. Recent advances in the knowledge of molecular tumor biology open the door to more adapted therapies according to individual alterations. Promising results in the adult anticancer drug development have not yet been translated into clinical practice. We report the activity in early pediatric oncology trials in Spain. Methods: All members of the Spanish Society of Pediatric Hematology Oncology (SEHOP) were contacted to obtain information about early trials open in each center. Results: 22 phase I and II trials were open as of May 2015: 15 for solid tumors (68 %) and 7 for hematological malignancies (32 %). Fourteen (64 %) were industry sponsored. Since 2010, four centers have joined the Innovative Therapies For Children With Cancer, an international consortium whose aim is developing novel therapies for pediatric cancers. A substantial number of studies have opened in these 5 years, improving the portfolio of trials for children. Results of recently closed trials show the contribution of Spanish investigators, the introduction of molecularly targeted agents and their benefits. Conclusions: Clinical trials are the way to evaluate new drugs, avoiding the use of off-label drugs that carry significant risks. The Spanish pediatric oncology community through the SEHOP is committed to develop and participate in collaborative academic trials, to favor the advancement and optimization of existing therapies in pediatric cancer. [ABSTRACT FROM AUTHOR]

Acanthamoeba is one of the most common free-living amoebas which is widespread in the environment and can infect humans, causing diseases such as keratitis and encephalitis. In this paper we examine for the first time the amebicidal activity of the family of cationic dendrimers nG-[Si{(CH)N(Me)(Et)(CH)NMe}2I] (where n denotes the generations: zero ( n = 0, x = 1), first ( n = 1, x = 4), and second ( n = 2, x = 8); for simplicity, they were named as 0G-CNN2, 1G-CNN8, and 2G-CNN16, respectively) against Acanthamoeba castellanii UAH-T17c3 trophozoites. In order to test the amebicidal activity, we cultured the strain A. castellanii UAH-T17c3 in PYG-Bactocasitone medium and later, we treated it with different concentrations of these dendrimers and monitored the effects and damage by optical count, flow cytometry, and scanning electron microscopy. The results showed that all the nanosystems assayed had a strong amebicidal activity. The dendrimer 1G-CNN8 was the most effective against the amoeba. In the morphology of treated throphozoites of A. castellanii UAH-T17c3 analyzed by light and scanning electron microscopy techniques, morphological changes were evident in amoeba cells, such as loss of pseudopodia, ectoplasm increase, roundness, and cellular lysis. Furthermore, flow cytometry results showed alterations in cell granularity, which was dose-time dependent. In conclusion, this family of cationic carbosilane dendrimers has a strong amebicidal activity against the trophozoites of A. castellanii UAH-T17c3 in vitro. They could potentially become new agents significant to the development of new amebicidal compounds for prevention and therapy of Acanthamoeba infections. [ABSTRACT FROM AUTHOR]

Cadmium causes oxidative damage and hence affects nitrogen assimilation. In the present work we tested the relationship between the inactivation of the enzymes involved in nitrogen assimilation pathway (glutamine synthetase (GS)/glutamate synthase (GOGAT)) and the protein oxidation in nodules of soybean ( Glycine max L.) plants under Cd2+ stress. Therefore, the effect of Cd2+ and reduced gluthatione (GSH) on GS and GOGAT activities, and protein abundance and oxidation were analyzed. Under the metal treatment, amino acids oxidative modification occurred, evidenced by the accumulation of carbonylated proteins, especially those of high molecular weight. When Cd2+ was present in the nutrient solution, although a decrease in GS and GOGAT activities was observed (17 and 52%, respectively, compared to controls), the protein abundance of both enzymes remained similar to control nodules. When GSH was added together with Cd2+ in the nutrient medium, it protected the nodule against Cd2+ induced oxidative damage, maintaining GS and GOGAT activities close to control values. These results allow us to conclude that the inactivation of the nitrogen assimilation pathway by Cd2+ in soybean nodules is due to an increment in GS and GOGAT oxidation that can be prevented by the soluble antioxidant GSH. [ABSTRACT FROM AUTHOR]

Information holographic storage is a very promising technique due to its high theoretical capacity. One of the key factors in developing holographic memories is the need for a suitable recording material which must have certain specific characteristics. In particular, in order to achieve a high storage density it is necessary to work with great thicknesses. One of the essential requirements for holographic memories to be competitive is that the material must have a thickness of 500 μm or more, but it is not easy to find such thicknesses with the photopolymers currently available. In this study, we develop a method of preparing layers of a polyvinyl alcohol/acrylamide based photopolymer approximately 1 mm thick. Optimization of this material makes it possible to obtain good results for the main holographic parameters; diffraction efficiency 70% and energetic sensitivity 50 mJ/cm[SUP2]. [ABSTRACT FROM AUTHOR]

STUDY DESIGN: A case of thoracic spinal cord compression due to tumoral calcinosis (TC) is reported. SETTING: Galiza, Spain. CASE REPORT: A 59-year-old man was admitted to our hospital with a 2-month history of gradual leg weakness and sensory deficit. The neurological examination revealed paraparesis with T12 sensory level. Magnetic resonance imaging (MRI) showed an extradural right posterolateral mass at T11-T12 level, resulting in a marked spinal cord compression. He underwent T11-T12 laminectomy and mass excision. Histological examination finally led to the diagnosis of TC. CONCLUSION: TC is an uncommon cause of mass lesions of the spine. Since there is no typical spine TC MRI appearance, the final diagnosis is done by histological studies. TC should be considered in differential diagnosis of spinal cord compression and constitutes a treatable cause of paraparesis. [ABSTRACT FROM AUTHOR]

STUDY DESIGN:: A case of thoracic spinal cord compression due to tumoral calcinosis (TC) is reported. SETTING:: Galiza, Spain. CASE REPORT:: A 59-year-old man was admitted to our hospital with a 2-month history of gradual leg weakness and sensory deficit. The neurological examination revealed paraparesis with T12 sensory level. Magnetic resonance imaging (MRI) showed an extradural right posterolateral mass at T11-T12 level, resulting in a marked spinal cord compression. He underwent T11-T12 laminectomy and mass excision. Histological examination finally led to the diagnosis of TC. CONCLUSION:: TC is an uncommon cause of mass lesions of the spine. Since there is no typical spine TC MRI appearance, the final diagnosis is done by histological studies. TC should be considered in differential diagnosis of spinal cord compression and constitutes a treatable cause of paraparesis.Spinal Cord (2003) 41, 413-416. doi:10.1038/sj.sc.3101419 [ABSTRACT FROM AUTHOR]

The effects of a partially purified aqueous extract of Solanum malacoxylon (SM) leaves and of an SM extract incubated with ruminal fluid (RF) prior to administration on intestinal phosphate and calcium absorption in rachitic rats were compared with 1α, 25-dihydroxy-vitamin D[1α,25-(OH)-D] using a duodenal loop in situ method. The time course responses elicited by both extracts were qualitatively similar to that of 1α, 25-(OH)-D. However, a single dose of SMRF was significantly more effective in stimulatingP absorption than an equivalent dose of SM. Part of this difference can be accounted for by incomplete saturation of the phosphate transport system with the level of SM employed. Treatment with rumen potentiated the effects of SM onCa absorption to a lesser extent. Extraction of SMRF with nonpolar organic solvents and purification of the lipid extract by chromatography on Silica Gel G thin-layer plates and on Sephadex LH-20 columns yield two fractions which promote intestinalP absorption. The bioactive fraction eluting first from the Sephadex LH-20 column migrates similarly as 1α,25-(OH)-D. The greater effectiveness of SMRF extracts on intestinal phosphate and calcium absorption may be tentatively attributed to the release of 1α,25-(OH)-D from the corresponding glycoside, shown previously to be present in SM, and to steroid modification during incubation with rumen. [ABSTRACT FROM AUTHOR]

Platelets of strontium hexaferrite (SrFe12O19, SFO), up to several micrometers in width, and tens of nanometers thick have been synthesized by a hydrothermal method. They have been studied by a combination of structural and magnetic techniques, with emphasis on Mössbauer spectroscopy and X-ray absorption based-measurements including spectroscopy and microscopy on the iron-L edges and the oxygen-K edge, allowing us to establish the differences and similarities between our synthesized nanostructures and commercial powders. The Mössbauer spectra reveal a greater contribution of iron tetrahedral sites in platelets in comparison to pure bulk material. For reference, high-resolution absorption and dichroic spectra have also been measured both from the platelets and from pure bulk material. The O-K edge has been reproduced by density functional theory calculations. Out-of-plane domains were observed with 180° domain walls less than 20 nm width, in good agreement with micromagnetic simulations. [ABSTRACT FROM AUTHOR]

Presents a correction to the article "Optimization of a 1 mm thick PVA/acrylamide recording material to obtain holographic memories: method of preparation and holographic properties," previously published in the journal.