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1.
Pediatr Blood Cancer ; 71(8): e31074, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38778452

RESUMEN

BACKGROUND: Adult- and adolescent-onset neuroblastomas are rare, with no established therapy. In addition, rare pheochromocytomas may harbor neuroblastic components. This study was designed to collect epidemiological, diagnostic and therapeutic data in order to better define the characteristics of malignant peripheral neuroblastic tumors (MPNT) and composite pheochromocytomas (CP) with MPNT. PROCEDURE: Fifty-nine adults and adolescents (aged over 15 years) diagnosed with a peripheral or composite neuroblastic tumor, who were treated in one of 17 institutions between 2000 and 2020, were retrospectively studied. RESULTS: Eighteen patients with neuroblastoma (NB) or ganglioneuroblastoma (GNB) had locoregional disease, and 28 patients had metastatic stage 4 NB. Among the 13 patients with CP, 12 had locoregional disease. Fifty-eight percent of the population were adolescents and young adults under 24 years of age. The probability of 5-year event-free survival (EFS) was 40% (confidence interval: 27%-53%). CONCLUSIONS: Outcomes were better for patients with localized tumor than for patients with metastases. For patients with localized tumor, in terms of survival, surgical treatment was the best therapeutic option. Multimodal treatment with chemotherapy, surgery, radiotherapy, and immunotherapy-based maintenance allowed long-term survival for some patients. Adolescent- and adult-onset neuroblastoma appeared to have specific characteristics associated with poorer outcomes compared to pediatric neuroblastoma. Nevertheless, complete disease control improved survival. The presence of a neuroblastic component in pheochromocytoma should be considered when making therapeutic management decisions. The development of specific tools/resources (Tumor Referral Board, Registry, biology, and trials with new agents or strategies) may help to improve outcomes for patients.


Asunto(s)
Neuroblastoma , Humanos , Estudios Retrospectivos , Adolescente , Masculino , Femenino , Neuroblastoma/terapia , Neuroblastoma/epidemiología , Neuroblastoma/patología , Neuroblastoma/mortalidad , Neuroblastoma/diagnóstico , Adulto , Adulto Joven , Francia/epidemiología , Tasa de Supervivencia , Persona de Mediana Edad , Neoplasias de las Glándulas Suprarrenales/terapia , Neoplasias de las Glándulas Suprarrenales/epidemiología , Neoplasias de las Glándulas Suprarrenales/patología , Neoplasias de las Glándulas Suprarrenales/mortalidad , Neoplasias de las Glándulas Suprarrenales/diagnóstico , Feocromocitoma/terapia , Feocromocitoma/epidemiología , Feocromocitoma/patología , Feocromocitoma/mortalidad , Estudios de Seguimiento , Terapia Combinada , Pronóstico , Edad de Inicio , Ganglioneuroblastoma/terapia , Ganglioneuroblastoma/patología , Ganglioneuroblastoma/epidemiología , Ganglioneuroblastoma/mortalidad , Anciano
2.
Clin Cancer Res ; 2024 May 24.
Artículo en Inglés | MEDLINE | ID: mdl-38787533

RESUMEN

PURPOSE: The study of cell free DNA (cfDNA) enables sequential analysis of tumor cell-specific genetic alterations in neuroblastoma patients. EXPERIMENTAL DESIGN: Eighteen patients with relapsing neuroblastoma having received Lorlatinib, a 3rd generation ALK inhibitor, were identified (SACHA national registry and/or in the institution). cfDNA was analyzed at relapse for 9 patients, and sequentially for 5 patients (blood/bone marrow plasma) by performing WGS library construction followed by ALK-targeted ddPCR of the hotspot mutations (F1174L, R1275Q, I1170N) (variant allele fraction (VAF) detection limit 0.1%) and WES to evaluate disease burden and clonal evolution, following comparison with tumor/germline WES. RESULTS: Overall response rate to Lorlatinib was 33% (CI 13-59%), with response observed in 6/10 cases without versus 0/8 cases with MYCN amplification (MNA). ALK VAFs correlated with the overall clinical disease status, with a VAF<0.1% in clinical remission, versus higher VAFs (>30%) at progression. Importantly, sequential ALK ddPCR detected relapse earlier than clinical imaging. cfDNA WES revealed new SNVs, not seen in the primary tumor, in all instances of disease progression after Lorlatinib treatment, indicating clonal evolution, including alterations in genes linked to tumor aggressivity (TP53) or novel targets (EGFR). Gene pathway analysis revealed an enrichment for genes targeting cell differentiation in emerging clones, and cell adhesion in persistent clones. Evidence of clonal hematopoiesis could be observed in follow-up samples. CONCLUSION: We demonstrate the clinical utility of combining ALK cfDNA ddPCR for disease monitoring and cfDNA WES for the study of clonal evolution and resistance mechanisms in neuroblastoma patients receiving ALK targeted therapy.

3.
Eur J Cancer ; 202: 114001, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38489858

RESUMEN

BACKGROUND: Addition of anti-GD2 antibodies to temozolomide-based chemotherapy has demonstrated increased antitumor activity and progression-free survival in patients with relapsed/progressive high-risk neuroblastoma. However, chemo-immunotherapy is not yet approved for this indication. This study presents the chemo-immunotherapy experience in patients with relapsed/progressive high-risk neuroblastoma treated within the off-label use program of the Neuroblastoma Committee of the French Society of Pediatric Oncology (SFCE). METHODS: Dinutuximab beta (dB) was administered alongside temozolomide-topotecan (TOTEM) or temozolomide-irinotecan (TEMIRI) at first disease relapse/progression or topotecan-cyclophosphamide (TopoCyclo) at further relapse/progression. Real-world data on demographics, treatment, antitumor activity and safety was collected from all patients after inclusion in SACHA-France (NCT04477681), a prospective national registry, which documents safety and efficacy data on innovative anticancer therapies prescribed to patients ≤ 25 years old as compassionate or off-label use. RESULTS: Between February 2021 and July 2023, 39 patients with confirmed relapsed/progressive high-risk neuroblastoma (median age 6 years, range 1-24) were treated with dB+TopoCyclo (n = 24) or dB+TOTEM/TEMIRI (n = 15) across 17 centers. In total, 163 chemo-immunotherapy cycles were administered, main toxicities were mild or moderate, with higher incidence of hematological adverse drug reactions with dB+TopoCyclo than dB+TOTEM/TEMIRI. Objective response rate was 42% for dB+TopoCyclo (CI95% 22-63%) and 40% for dB+TOTEM/TEMIRI (CI95% 16-68%). CONCLUSION: Similar objective response rates for dB+TopoCyclo and dB+TOTEM/TEMIRI in patients with relapsed/progressive high-risk neuroblastoma emphasize the importance of chemo-immunotherapy, irrespective of the chemotherapy backbone.


Asunto(s)
Anticuerpos Monoclonales , Neuroblastoma , Topotecan , Niño , Humanos , Lactante , Preescolar , Adolescente , Adulto Joven , Adulto , Topotecan/efectos adversos , Temozolomida/uso terapéutico , Estudios Prospectivos , Supervivencia sin Enfermedad , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Recurrencia Local de Neoplasia/patología , Neuroblastoma/patología , Ciclofosfamida , Irinotecán/uso terapéutico , Inmunoterapia/efectos adversos , Recurrencia
4.
Nat Commun ; 14(1): 7884, 2023 Nov 30.
Artículo en Inglés | MEDLINE | ID: mdl-38036539

RESUMEN

Wilms tumors are highly curable in up to 90% of cases with a combination of surgery and radio-chemotherapy, but treatment-resistant types such as diffuse anaplastic Wilms tumors pose significant therapeutic challenges. Our multi-omics profiling unveils a distinct desert-like diffuse anaplastic Wilms tumor subtype marked by immune/stromal cell depletion, TP53 alterations, and cGAS-STING pathway downregulation, accounting for one-third of all diffuse anaplastic cases. This subtype, also characterized by reduced CD8 and CD3 infiltration and active oncogenic pathways involving histone deacetylase and DNA repair, correlates with poor clinical outcomes. These oncogenic pathways are found to be conserved in anaplastic Wilms tumor cell models. We identify histone deacetylase and/or WEE1 inhibitors as potential therapeutic vulnerabilities in these tumors, which might also restore tumor immunogenicity and potentially enhance the effects of immunotherapy. These insights offer a foundation for predicting outcomes and personalizing treatment strategies for aggressive pediatric Wilms tumors, tailored to individual immunological landscapes.


Asunto(s)
Neoplasias Renales , Tumor de Wilms , Niño , Humanos , Neoplasias Renales/genética , Neoplasias Renales/terapia , Neoplasias Renales/metabolismo , Tumor de Wilms/genética , Tumor de Wilms/terapia , Histona Desacetilasas
5.
Pediatr Blood Cancer ; 70(10): e30561, 2023 10.
Artículo en Inglés | MEDLINE | ID: mdl-37430425

RESUMEN

Paediatric palliative care aims to support children and young people with life-limiting or life-threatening conditions, and their families, from the time of diagnosis. Early integration within oncology has been recognised as having benefits for all involved, whatever the outcome may be. Through improved communication and advance care planning, it enables user-centred care, where concerns about quality of life, preferences and values are given the same relevance as cutting-edge therapy. Challenges to the integration of palliative care within paediatric oncology include raising awareness and providing education, whilst searching for the best care model and adapting to an ever-changing therapeutic scenario.


Asunto(s)
Planificación Anticipada de Atención , Neoplasias , Niño , Humanos , Adolescente , Cuidados Paliativos , Calidad de Vida , Oncología Médica , Neoplasias/diagnóstico , Neoplasias/terapia
6.
Pediatr Blood Cancer ; 70 Suppl 2: e30110, 2023 05.
Artículo en Inglés | MEDLINE | ID: mdl-36451260

RESUMEN

This review highlights the role of several immunomodulating elements contributing to the tumor microenvironment of various pediatric renal tumors including Wilms tumor. The roles of innate and adaptive immune cells in renal tumors are summarized as well as immunomodulatory cytokines and other proteins. The expression and the predictive role of checkpoint modulators like PD-L1 and immunomodulating proteins like glypican-3, B7-H3, COX-2 are highlighted with a translational view toward potential therapeutic innovations. We further discuss the current state of preclinical models in advancing this field of study. Finally, examples of clinical trials of immunomodulating strategies such as monoclonal antibodies and chimeric antigen receptor T (CAR-T) cells for relapsed/refractory/progressive pediatric renal tumors are described.


Asunto(s)
Neoplasias Renales , Microambiente Tumoral , Niño , Humanos , Antígeno B7-H1 , Neoplasias Renales/tratamiento farmacológico , Inmunomodulación , Anticuerpos Monoclonales/uso terapéutico
7.
Pediatr Blood Cancer ; 70(3): e30107, 2023 03.
Artículo en Inglés | MEDLINE | ID: mdl-36453594

RESUMEN

AIM: The number of lymph nodes (LN) that should be sampled during nephrectomy for Wilms tumour (WT) remains controversial but of utmost importance for staging purposes. The aim of this French national retrospective study of patients enrolled in SIOPWT2001 trial was to analyse the number of LN sampled according to their site and to determine if the number of six asked by the International Society of Paediatric Oncology - Renal Tumour Study Group (SIOP-RTSG) UMBRELLA protocol is achievable. METHODS: We reviewed the data collected on central pathology review forms from 2002 to 2014 for only unilateral WT. LN were divided whether they were clearly identified by surgeons at nephrectomy or only found by pathologists on the nephrectomy specimen. RESULTS: A total of 539 patients (240 male/299 female) were included (458 localized/81 metastatic). Median age at surgery was 41.3 months [0-189]. The number of LN sampled was 0, 1-6, ≥7 and unknown in 69 (12.8%), 293 (54.3%), 160 (29.7%) and 17 (3.2%) cases, respectively. The number of patients with sampled LN were higher if LN were identified by both the pathologist and the surgeon (n = 231, 42.8%) (p = < .001). At least one invaded LN (LN+) was found in 66 patients (12.2%), more than half being found among patients having LN sampled by both pathologist and surgeon (p < .001). The mean number of identified LN was six if no LN+ was detected on final histological analysis, while it was 11 in case of LN+ (p < .001). CONCLUSIONS: The aim of sampling more than six LN is achievable, but only with the active collaboration of both surgeons and pathologists.


Asunto(s)
Neoplasias Renales , Tumor de Wilms , Niño , Preescolar , Femenino , Humanos , Masculino , Objetivos , Neoplasias Renales/cirugía , Neoplasias Renales/patología , Ganglios Linfáticos/cirugía , Ganglios Linfáticos/patología , Estadificación de Neoplasias , Estudios Retrospectivos , Tumor de Wilms/cirugía , Tumor de Wilms/patología , Recién Nacido , Lactante , Adolescente , Ensayos Clínicos como Asunto
8.
Pediatr Blood Cancer ; 69(12): e29950, 2022 12.
Artículo en Inglés | MEDLINE | ID: mdl-36057861

RESUMEN

OBJECTIVE: To describe locoregional failure (LRF) after postoperative flank radiotherapy (RT) among French patients with nephroblastoma included in the Société Internationale d'Oncologie Pédiatrique (SIOP)-2001 protocol. PATIENTS AND METHODS: In selected SIOP-2001 patients, planning with simulation computed tomography (CT) scan and posttreatment CT scan demonstrating LRF were registered and analyzed. LRF was contoured and classified as in-field, marginal or out-of-field according to dose distribution. RESULTS: Total 316 French SIOP-2001 patients were treated with postoperative RT. Three patients with nephroblastoma developed LRF after flank RT. All failures were located within the retroperitoneum. In two patients, the relapse was within the RT field and in one it was classified as marginal. CONCLUSION: LRF after postoperative flank RT for nephroblastoma was rare and exclusively situated in the retroperitoneum. These results point out this region as the most at risk of local relapse. A prospective evaluation of a target volume restricted to the retroperitoneum allowing the use of modern and highly conformal radiation techniques in order to decrease dose to normal tissues shall be encouraged.


Asunto(s)
Neoplasias Renales , Radioterapia Conformacional , Tumor de Wilms , Humanos , Recurrencia Local de Neoplasia , Tumor de Wilms/radioterapia , Tumor de Wilms/cirugía , Tumor de Wilms/tratamiento farmacológico , Estudios de Cohortes , Neoplasias Renales/radioterapia , Neoplasias Renales/cirugía , Neoplasias Renales/tratamiento farmacológico
9.
Bull Cancer ; 109(4): 491-504, 2022 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-35428456

RESUMEN

BACKGROUND: NUT carcinoma (NC), defined by the presence of the NUTM1 rearrangement, is an aggressive tumour associated with poor prognosis. This rare cancer is underdiagnosed and difficult to treat. OBJECTIVE AND METHODS: The primary objective of this review is to describe the clinical, radiological and laboratory features of NC in young patients. The secondary objective is to propose a consensual strategy for the French very Rare Tumour group (FRACTURE group). RESULTS: NUT-specific antibody immunostaining in cases of undifferentiated or poorly differentiated carcinoma may demonstrate the specific NUT gene rearrangement. NCs are frequently advanced stage at diagnosis and the outcome remains poor despite a global strategy that generally includes conventional combination chemotherapy with wide local therapy (surgery, radiotherapy). Chemosensitivity is frequently only transient. CONCLUSION: Recent data have shown that new targeted drugs (histone deacetylase and bromodomain and extra-terminal protein inhibitors) are promising, but their role has yet to be evaluated in NC. Centralized data review is necessary to improve our knowledge of paediatric NC. We propose a multimodal strategy based on published data and their personal experience.


Asunto(s)
Carcinoma , Proteínas Nucleares , Adolescente , Carcinoma/terapia , Niño , Humanos , Proteínas Nucleares/metabolismo , Factores de Transcripción , Adulto Joven
10.
Bull Cancer ; 107(9): 934-945, 2020 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-32896369

RESUMEN

The esthesioneuroblastoma (ENB) is characterized as a rare malignant sinonasal tumor of neuroectodermal origin. Its starting point is the olfactory epithelium located in the upper part of the nasal cavities. Different nomenclatures have been proposed, but the most common are "esthesioneuroblastoma" and "olfactory neuroblastoma". ENBs have a bimodal distribution and mainly occur in teenagers, young adults and people aged 50-60. It is a very rare tumor in pediatrics since only around 100 cases have been reported so far. Within ENBs, we can distinguish tumors with different biological behavior ranging from localized forms with slow evolution to aggressive and metastatic forms at onset. In addition, precisely diagnosing undifferentiated tumors and distinguishing them from other etiologies of sinonasal tumors are sometime difficult. Added to its very low incidence, these characteristics make the study of ENB complicated. The standard treatment currently includes broad surgery followed by radiation therapy in localized resectable tumors. Neoadjuvant chemotherapy is indicated in large unresectable tumors and in metastatic forms. However, in certain indications, such as high-grade operable tumors, the role of perioperative chemotherapy remains to be defined. The objective of this analysis is to detail current knowledge regarding ENBs' epidemiological, biological, clinical and radiological characteristics as well as how to manage ENB in young patients.


Asunto(s)
Estesioneuroblastoma Olfatorio/diagnóstico , Estesioneuroblastoma Olfatorio/terapia , Cavidad Nasal , Neoplasias Nasales/diagnóstico , Neoplasias Nasales/terapia , Adolescente , Niño , Humanos , Estadificación de Neoplasias , Adulto Joven
11.
Bull Cancer ; 107(10): 963-971, 2020 Oct.
Artículo en Francés | MEDLINE | ID: mdl-32950242

RESUMEN

Soft tissue sarcomas in children are rare tumor, representing around 6 to 7% of children cancer. They spread mostly sporadically (90%) and therefore are rarely associated to an underlying constitutional genetic disease (10%). About half of those sarcomas are rhabdomyosarcomas and the others are a very heterogenous histologic group with various bio-pathologies and prognosis. Clinical presentation is mainly a soft tissue lump often difficult to distinguish from more frequent benign causes (malformative, infectious, benign, or pseudotumor). Inappropriate initial diagnosis work-up has a strong impact on soft tissue sarcomas' prognosis. Adapted complementary investigations (first ultrasound and MRI) are important to compile arguments for a malign origin and to indicate a biopsy. However, predictive value of imaging exams still remains imperfect, and histological analysis by percutaneous image-guided biopsy and sometimes by surgical biopsy is often necessary. Authors realize an update on optimal diagnostic pathway including molecular tests in presence of a soft tissue mass in a child.


Asunto(s)
Sarcoma/diagnóstico , Neoplasias de los Tejidos Blandos/diagnóstico , Humanos
12.
Pediatr Blood Cancer ; 67(4): e28154, 2020 04.
Artículo en Inglés | MEDLINE | ID: mdl-31930719

RESUMEN

BACKGROUND: Esthesioneuroblastoma (ENB) is a rare neuroectodermal tumor that seldom occurs during childhood. Multimodal treatments are currently proposed, but the place of each therapy is still in debate. Our objective is to describe clinical evolution, especially the pattern of relapses and determine contributors to tumor progression. PROCEDURE: Medical charts of all children (≤18 years) affected by ENB treated in France from January 1990 to December 2015 were retrospectively analyzed. RESULTS: Eighteen patients were selected (10 males). Median age at diagnosis was 12.2 years (0.9-18). Tumor extension was Kadish stage A (n = 1), B (n = 3), C (n = 10), and D (n = 4). Hyams histological grades were I (n = 1), II (n = 3), III (n = 6), and IV (n = 6) (in two cases not defined). Initial cervical nodal spread was assessed by magnetic resonance imaging (n = 15), computed tomography scan (n = 16), fluorodeoxyglucose-positron emission tomography-computed tomography (n = 7), and cytological/histological analysis (n = 2). N1 stage was confirmed by imaging in two of 18 cases and one of two cases had cervical node dissection with neck irradiation (58 Gy). After a median follow-up of survivors of 7.6 years (3.8-17.9), 10 patients developed neuromeningeal progression, whereas no cervical nodal relapse occurred and only eight survived. Both 5-year overall and event-free survival rates were 44.4% (±11.7%). CONCLUSIONS: The poor prognosis is mainly related to neuromeningeal dissemination that should be considered during treatment strategy. However, cervical lymph node relapse is rare.


Asunto(s)
Estesioneuroblastoma Olfatorio/patología , Cavidad Nasal/patología , Recurrencia Local de Neoplasia/patología , Neoplasias Nasales/patología , Enfermedades Raras/patología , Adolescente , Niño , Preescolar , Terapia Combinada , Estesioneuroblastoma Olfatorio/terapia , Femenino , Estudios de Seguimiento , Humanos , Lactante , Recién Nacido , Masculino , Recurrencia Local de Neoplasia/terapia , Neoplasias Nasales/terapia , Pronóstico , Enfermedades Raras/terapia , Estudios Retrospectivos , Tasa de Supervivencia
15.
J Alzheimers Dis ; 31(1): 13-20, 2012.
Artículo en Inglés | MEDLINE | ID: mdl-22495345

RESUMEN

Tau proteins and amyloid-ß (Aß) peptides are the current recognized cerebrospinal fluid (CSF) biomarkers used as an aid in the diagnosis of Alzheimer's disease (AD). However, there is no consensus on their clinical use due to non-qualified cut-off values, probably related to the observed high pre-analytical and analytical variability. Standardized pre-analytical protocols have therefore been proposed. Importantly, these recommend the use of polypropylene collection/sampling tubes while, to date, no broad comparison of these types of tubes has been conducted. In this study, we first compared, as part of a real clinical workflow, the impact of four different collection tubes on the CSF concentration of Aß peptides (Aß42, Aß40) and total (hTau) and phosphorylated (P-Tau181P) tau proteins measured using routine ELISA kits. We then extended this study to 11 polypropylene tubes used by different clinical laboratories, and investigated their plastic polymer composition using differential scanning calorimetry and Fourier Transformed Infrared spectroscopy. Significant concentration variations linked solely to the use of different types of tubes were observed. This was particularly marked for Aß peptides, with >50% disparity occurring in less than five minutes. Polymer composition analysis revealed that most polypropylene tubes were in fact copolymers with at least polyethylene. There was no clear correlation between tube composition and pre-analytical behavior. Our results show that the use of polypropylene tubes does not guarantee satisfactory pre-analytical behavior. They also point to collection/sampling tubes being a major pre-analytical source of variability that could impact the significance of AD biological diagnosis.


Asunto(s)
Enfermedad de Alzheimer/líquido cefalorraquídeo , Enfermedad de Alzheimer/diagnóstico , Péptidos beta-Amiloides/líquido cefalorraquídeo , Errores Diagnósticos , Proteínas tau/líquido cefalorraquídeo , Ensayo de Inmunoadsorción Enzimática , Análisis de Fourier , Humanos , Fosforilación , Riesgo , Espectrofotometría Infrarroja , Estadísticas no Paramétricas , Factores de Tiempo
16.
Acta Neuropathol ; 124(1): 37-50, 2012 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-22370907

RESUMEN

α-Synuclein is the major protein associated with Lewy body dementia, Parkinson's disease and multiple system atrophy. Since α-synuclein is present in the brain in physiological conditions as a presynaptic protein, it is crucial to characterize disease-associated modifications to develop an in vivo biomarker. With the aim to develop antibodies showing high specificity and sensitivity for disease-associated α-synuclein, synthetic peptides containing different amino acid sequences were used for immunization of mice. After generation of α-synuclein aggregates, ELISA and immunoblotting were used to test the specificity of antibodies. Tissue microarray sections originating from different human α-synucleinopathies were used to compare immunostaining with other, commercially available antibodies. Immunization of mice with the peptide TKEGVVHGVATVAE (amino acid 44-57 of α-synuclein) resulted in the generation of a monoclonal antibody (5G4), which was able to bind aggregated α-synuclein preparation in sandwich ELISA or coated on magnetic beads. 5G4 proved to be superior to other antibodies in comparative immunohistochemical studies by revealing more widespread and distinct α-synuclein pathology. Immunoblotting of human brain tissue revealed an additional band seen in dementia with Lewy bodies, whereas the band representing monomeric α-synuclein was very weak or lacking. In summary, the 5G4 antibody is most promising for re-evaluation of archival material and may offer new perspective for the development of in vivo diagnostic assays for detecting disease-associated α-synuclein in body fluids.


Asunto(s)
Anticuerpos/metabolismo , Encefalopatías/patología , Encéfalo/metabolismo , Encéfalo/patología , alfa-Sinucleína/inmunología , Ensayo de Inmunoadsorción Enzimática/métodos , Degeneración Lobar Frontotemporal/patología , Humanos , Inmunohistoquímica , Atrofia de Múltiples Sistemas/patología , Neuronas/metabolismo , Neuronas/patología , Enfermedad de Parkinson/patología , alfa-Sinucleína/metabolismo
18.
Ann Biol Clin (Paris) ; 68(2): 163-72, 2010.
Artículo en Francés | MEDLINE | ID: mdl-20348049

RESUMEN

In order to overcome the stop marketing by Biorad company of automated high performance liquid chromatograph with UV detection (Remedi), we developed a gas chromatography-mass spectrometry (GC-MS) to detect and to give an approximation of the overdose of molecules frequently encountered in drug intoxications. Therefore two hundred eighty seventeen blood samples were collected over a period of one year and allowed us to evaluate and compare the performance of these two techniques. As identification, GC-MS does not identify all molecules detected by Remedi in 24.2% of cases; there is a lack of sensitivity for opiates and the systematic absence of certain molecules such as betablockers. However, in 75.8% of cases the GC-MS detects all molecules found by Remedi and other molecules such as meprobamate, paracetamol, benzodiazepines and phenobarbital. The concentrations obtained are interpreted in terms of overdose showed 15.7% of discrepancy and 84.3% of concordance between the two techniques. The GC-MS technique described here is robust, fast and relatively simple to implement; the identification is facilitated by macro commands and the semi quantification remains manual. Despite a sequence of cleaning the column after each sample, carryover of a sample to the next remains possible. This technique can be used for toxicologic screening in acute intoxications. Nevertheless it must be supplemented by a HPLC with UV detection if molecules such as betablockers are suspected.


Asunto(s)
Sobredosis de Droga/sangre , Urgencias Médicas , Detección de Abuso de Sustancias/métodos , Automatización , Cromatografía Líquida de Alta Presión/métodos , Diazepam/sangre , Sobredosis de Droga/epidemiología , Cromatografía de Gases y Espectrometría de Masas/métodos , Humanos , Sensibilidad y Especificidad , Trastornos Relacionados con Sustancias/sangre , Trastornos Relacionados con Sustancias/epidemiología
19.
Biochimie ; 90(4): 640-7, 2008 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-18086573

RESUMEN

Today, the information for generating reliable protein-protein complex datasets is not directly accessible from PDB structures. Moreover, in X-ray protein structures, different types of contacts can be observed between proteins: contacts in homodimers or inside heterocomplexes considered to be specific, and contacts induced by crystallogenesis processes, considered to be non-specific. However, none of the databases giving access to protein-protein complexes allows the crystallographic interfaces to be distinguished from the biological interfaces. For this reason we developed PPIDD (Protein-Protein Interface Description Database), an innovative tool, which allows the extraction and visualisation of biological protein-protein interfaces from an annotated subset of crystallographic structures of proteins. This tool is focused on the description of protein-protein interfaces corresponding to well-identified classes of protein assemblies. It permits the representation of any of these protein-protein assemblies (duplex) and their interfaces as well as the export of the corresponding molecular structures under a flexible format, which is an extension of the PDBML. Moreover, PPIDD facilitates the construction of subsets of interfaces presenting user-specified common characteristics, to enhance the understanding of the determinants of specific protein-protein interactions.


Asunto(s)
Bases de Datos de Proteínas , Almacenamiento y Recuperación de la Información/métodos , Conformación Proteica , Proteínas/química , Interfaz Usuario-Computador , Cristalografía por Rayos X , Internet , Modelos Moleculares , Mapeo de Interacción de Proteínas , Análisis de Secuencia de Proteína
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