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1.
Exp Hematol Oncol ; 13(1): 38, 2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38581035

RESUMO

Rhabdomyosarcoma (RMS), such as other childhood tumors, has witnessed treatment advancements in recent years. However, high-risk patients continue to face poor survival rates, often attributed to the presence of the PAX3/7-FOXO1 fusion proteins, which has been associated with metastasis and treatment resistance. Despite efforts to directly target these chimeric proteins, clinical success remains elusive. In this study, the main aim was to address this challenge by investigating regulators of FOXO1. Specifically, we focused on TRIB3, a potential regulator of the fusion protein in RMS. Our findings revealed a prominent TRIB3 expression in RMS tumors, highlighting its correlation with the presence of fusion protein. By conducting TRIB3 genetic inhibition experiments, we observed an impairment on cell proliferation. Notably, the knockdown of TRIB3 led to a decrease in PAX3-FOXO1 and its target genes at protein level, accompanied by a reduction in the activity of the Akt signaling pathway. Additionally, inducible silencing of TRIB3 significantly delayed tumor growth and improved overall survival in vivo. Based on our analysis, we propose that TRIB3 holds therapeutic potential for treating the most aggressive subtype of RMS. The findings herein reported contribute to our understanding of the underlying molecular mechanisms driving RMS progression and provide novel insights into the potential use of TRIB3 as a therapeutic intervention for high-risk RMS patients.

2.
Int J Mol Sci ; 22(23)2021 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-34884726

RESUMO

The Wnt/ß-catenin signaling pathway plays a pivotal role during embryogenesis and its deregulation is a key mechanism in the origin and progression of several tumors. Wnt antagonists have been described as key modulators of Wnt/ß-catenin signaling in cancer, with Dickkopf-1 (DKK-1) being the most studied member of the DKK family. Although the therapeutic potential of DKK-1 inhibition has been evaluated in several diseases and malignancies, little is known in pediatric tumors. Only a few works have studied the genetic inhibition and function of DKK-1 in rhabdomyosarcoma. Here, for the first time, we report the analysis of the therapeutic potential of DKK-1 pharmaceutical inhibition in rhabdomyosarcoma, the most common soft tissue sarcoma in children. We performed DKK-1 inhibition via shRNA technology and via the chemical inhibitor WAY-2626211. Its inhibition led to ß-catenin activation and the modulation of focal adhesion kinase (FAK), with positive effects on in vitro expression of myogenic markers and a reduction in proliferation and invasion. In addition, WAY-262611 was able to impair survival of tumor cells in vivo. Therefore, DKK-1 could constitute a molecular target, which could lead to novel therapeutic strategies in RMS, especially in those patients with high DKK-1 expression.


Assuntos
Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Naftalenos/uso terapêutico , Piperidinas/uso terapêutico , Pirimidinas/uso terapêutico , Rabdomiossarcoma/tratamento farmacológico , Via de Sinalização Wnt/efeitos dos fármacos , beta Catenina/metabolismo , Animais , Estudos de Casos e Controles , Linhagem Celular Tumoral , Proteína-Tirosina Quinases de Adesão Focal/metabolismo , Humanos , Camundongos SCID , Terapia de Alvo Molecular , Músculos/metabolismo , Proteína MyoD/metabolismo , Miogenina/metabolismo , Naftalenos/farmacologia , Piperidinas/farmacologia , Pirimidinas/farmacologia , RNA Interferente Pequeno/uso terapêutico , Rabdomiossarcoma/etiologia , Rabdomiossarcoma/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto
3.
Pharmaceuticals (Basel) ; 14(8)2021 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-34451907

RESUMO

The Wnt signaling pathway regulates crucial aspects such as cell fate determination, cell polarity and organogenesis during embryonic development. Wnt pathway deregulation is a hallmark of several cancers such as lung, gastric and liver cancer, and has been reported to be altered in others. Despite the general agreement reached by the scientific community on the oncogenic potential of the central components of the pathway, the role of the antagonist proteins remains less clear. Deregulation of the pathway may be caused by overexpression or downregulation of a wide range of antagonist proteins. Although there is growing information related to function and regulation of Dickkopf (DKK) proteins, their pharmacological potential as cancer therapeutics still has not been fully developed. This review provides an update on the role of DKK proteins in cancer and possible potential as therapeutic targets for the treatment of cancer; available compounds in pre-clinical or clinical trials are also reviewed.

4.
Stem Cells Int ; 2017: 7507380, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28243259

RESUMO

Rhabdomyosarcoma (RMS) is the most common type of soft tissue sarcoma in children and can be divided into two main subtypes: embryonal (eRMS) and alveolar (aRMS). Among the cellular heterogeneity of tumors, the existence of a small fraction of cells called cancer stem cells (CSC), thought to be responsible for the onset and propagation of cancer, has been demonstrated in some neoplasia. Although the existence of CSC has been reported for eRMS, their existence in aRMS, the most malignant subtype, has not been demonstrated to date. Given the lack of suitable markers to identify this subpopulation in aRMS, we used cancer stem cell-enriched supracellular structures (spheres and holoclones) to study this subpopulation. This strategy allowed us to demonstrate the capacity of both aRMS and eRMS cells to form these structures and retain self-renewal capacity. Furthermore, cells contained in spheres and holoclones showed significant Hedgehog pathway induction, the inhibition of which (pharmacologic or genetic) impairs the formation of both holoclones and spheres. Our findings point to a crucial role of this pathway in the maintenance of these structures and suggest that Hedgehog pathway targeting in CSC may have great potential in preventing local relapses and metastases.

5.
Pediatr Infect Dis J ; 35(12): 1350-1351, 2016 12.
Artigo em Inglês | MEDLINE | ID: mdl-27626919

RESUMO

Acanthamoeba infections are rare and mostly occur in immunocompromised patients. Most of the reported cases after stem cell transplantation have been diagnosed postmortem. We present the case of a 3-year-old boy with chronic graft versus host disease post hematopoietic transplantation, who was successfully treated for Acanthamoeba.


Assuntos
Amebíase , Doença Enxerto-Hospedeiro/complicações , Transplante de Células-Tronco Hematopoéticas , Sinusite , Acanthamoeba , Amebíase/complicações , Amebíase/tratamento farmacológico , Amebíase/parasitologia , Amebicidas/uso terapêutico , Anfotericina B/uso terapêutico , Pré-Escolar , Humanos , Masculino , Mucosa Nasal/parasitologia , Mucosa Nasal/patologia , Sinusite/complicações , Sinusite/tratamento farmacológico , Sinusite/parasitologia
6.
Haematologica ; 101(3): 279-85, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26928249

RESUMO

L-asparaginase is an integral component of therapy for acute lymphoblastic leukemia. However, asparaginase-related complications, including the development of hypersensitivity reactions, can limit its use in individual patients. Of considerable concern in the setting of clinical allergy is the development of neutralizing antibodies and associated asparaginase inactivity. Also problematic in the use of asparaginase is the potential for the development of silent inactivation, with the formation of neutralizing antibodies and reduced asparaginase activity in the absence of a clinically evident allergic reaction. Here we present guidelines for the identification and management of clinical hypersensitivity and silent inactivation with Escherichia coli- and Erwinia chrysanthemi- derived asparaginase preparations. These guidelines were developed by a consensus panel of experts following a review of the available published data. We provide a consensus of expert opinions on the role of serum asparaginase level assessment, indications for switching asparaginase preparation, and monitoring after change in asparaginase preparation.


Assuntos
Antineoplásicos/uso terapêutico , Asparaginase/uso terapêutico , Gerenciamento Clínico , Hipersensibilidade a Drogas/prevenção & controle , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Anticorpos Neutralizantes/biossíntese , Anticorpos Neutralizantes/sangue , Antineoplásicos/sangue , Antineoplásicos/farmacocinética , Asparaginase/antagonistas & inibidores , Asparaginase/sangue , Asparaginase/farmacocinética , Consenso , Dickeya chrysanthemi/genética , Dickeya chrysanthemi/metabolismo , Hipersensibilidade a Drogas/diagnóstico , Hipersensibilidade a Drogas/etiologia , Monitoramento de Medicamentos , Substituição de Medicamentos , Escherichia coli/genética , Escherichia coli/metabolismo , Expressão Gênica , Humanos , Leucemia-Linfoma Linfoblástico de Células Precursoras/sangue , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologia , Proteínas Recombinantes/sangue , Proteínas Recombinantes/farmacocinética , Proteínas Recombinantes/uso terapêutico
7.
Oncotarget ; 7(8): 9271-87, 2016 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-26824183

RESUMO

Despite multimodal therapies, a high percentage of high-risk neuroblastoma (NB) become refractory to current treatments, most of which interfere with cell cycle and DNA synthesis or function, activating the DNA damage response (DDR). In cancer, this process is frequently altered by deregulated expression or function of several genes which contribute to multidrug resistance (MDR). MicroRNAs are outstanding candidates for therapy since a single microRNA can modulate the expression of multiple genes of the same or different pathways, thus hindering the development of resistance mechanisms by the tumor. We found several genes implicated in the MDR to be overexpressed in high-risk NB which could be targeted by microRNAs simultaneously. Our functional screening identified several of those microRNAs that reduced proliferation of chemoresistant NB cell lines, the best of which was miR-497. Low expression of miR-497 correlated with poor patient outcome. The overexpression of miR-497 reduced the proliferation of multiple chemoresistant NB cell lines and induced apoptosis in MYCN-amplified cell lines. Moreover, the conditional expression of miR-497 in NB xenografts reduced tumor growth and inhibited vascular permeabilization. MiR-497 targets multiple genes related to the DDR, cell cycle, survival and angiogenesis, which renders this molecule a promising candidate for NB therapy.


Assuntos
Permeabilidade Capilar/genética , Ciclo Celular/genética , Sobrevivência Celular/genética , MicroRNAs/genética , Neovascularização Patológica/genética , Neuroblastoma/genética , Neuroblastoma/patologia , Animais , Apoptose/genética , Linhagem Celular Tumoral , Proliferação de Células/genética , Doxiciclina/uso terapêutico , Resistencia a Medicamentos Antineoplásicos , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Camundongos , Camundongos Nus , MicroRNAs/biossíntese , Neuroblastoma/tratamento farmacológico , Neuroblastoma/mortalidade , Resultado do Tratamento , Ensaios Antitumorais Modelo de Xenoenxerto
8.
Scand J Psychol ; 56(3): 306-14, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25660107

RESUMO

Surviving childhood cancer has multiple implications on both physical and psychological domains of the individual. However, its study and possible effects on health-related quality of life (HRQoL) outcomes of adolescent survivors has been understudied. The objective of this study was twofold; to assess positive and negative cancer-related consequences (psychosocial and physical) in a sample of adolescent cancer survivors and to explore their relationship with HRQoL outcomes. Forty-one participants answered two questions about positive and negative consequences in the aftermath of cancer and filled in the KIDSCREEN-52 self-reported version. Data were analysed using mixed methods approach. Overall, 87.8% of the studied sample identified positive consequences and 63.4% negative consequences in survivorship. Four positive categories and five negative categories with regard to cancer-related consequences were found. Changed perspectives in life narratives seem to be the positive consequence more related to HRQoL (physical well-being, mood & emotions, autonomy, social support & peers), followed by useful life experience (physical well-being, autonomy, social support & peers). Psychological impact was the most referred negative consequence with a significant detrimental effect on social support and peers HRQoL dimension. Even if the majority of survivors reported benefit finding in the aftermath of cancer, concomitant positive and negative consequences have been found. However, findings only reveal a significant relationship between positive narratives and HRQoL, and negative consequences do not seem to have a significant influence on overall HRQoL in survivorship.


Assuntos
Adaptação Psicológica/fisiologia , Emoções/fisiologia , Neoplasias/psicologia , Qualidade de Vida/psicologia , Sobreviventes/psicologia , Adolescente , Afeto/fisiologia , Feminino , Nível de Saúde , Humanos , Masculino , Grupo Associado , Autonomia Pessoal , Apoio Social , Inquéritos e Questionários , Adulto Jovem
9.
Pediatrics ; 133(1): e263-6, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24366994

RESUMO

Diencephalic syndrome is a rare condition associated with central nervous system tumors. The most common presentation is secondary failure to thrive with proper caloric intake and no statural impairment. Despite the importance of this syndrome, little is known of its pathophysiology. Some reports have documented changes in human growth hormone and insulin levels at the onset, whereas others have described endocrine disorders of hypothalamic insufficiency resulting from surgery of the tumor. It has been suggested that the hormonal changes described, such as increased human growth hormone and ghrelin or decreased insulin and leptin levels, are related to a patient's BMI. These findings support the role of these 4 hormones as indicators of the patient's nutritional status but not as mediators or potential therapeutic targets of the disease. We report the case of an infant who initially presented with tumor progression and, after chemotherapy, progressive weight gain and reduced tumor size. Because he presented no hormonal deficiencies or obesity after therapy, we were able to analyze his hormonal status uninfluenced by effects of metabolic treatment or excess weight. Although ghrelin and leptin levels have been related to nutritional status, our patient's leptin levels fell when tumor size decreased and weight increased: an extraordinary finding because leptin concentration is expected to increase with weight gain. This paradoxical response suggests that leptin may be dysregulated in diencephalic syndrome or that the diencephalic astrocytoma may have had an effect on leptin secretion.


Assuntos
Astrocitoma/sangue , Neoplasias Hipotalâmicas/sangue , Leptina/sangue , Astrocitoma/diagnóstico , Biomarcadores/sangue , Humanos , Neoplasias Hipotalâmicas/diagnóstico , Lactente , Masculino , Síndrome
10.
Span J Psychol ; 16: E1, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23866202

RESUMO

This research assesses Health-Related Quality of Life (HRQoL) in a Spanish sample of adolescent cancer survivors, and analyzes the relationship between HRQoL, coping styles and physical exercise. Forty-two survivors (12-19 years), who were ≥ 1 year of remission, completed standardized measures of HRQoL (CHIP-AE), coping strategies (ACS) and physical exercise (AECEF). Mean scores in all HRQoL domains were within normative values. Multiple regression analysis revealed that physical exercise and productive coping were related to higher HRQoL, whereas non-productive coping was related to lower HRQoL. This sample of survivors reported good levels of HRQoL, which are mediated by coping styles and physical exercise.


Assuntos
Adaptação Psicológica , Exercício Físico/psicologia , Neoplasias/psicologia , Qualidade de Vida , Sobreviventes/psicologia , Adolescente , Criança , Estudos Transversais , Feminino , Nível de Saúde , Humanos , Leucemia/psicologia , Modelos Lineares , Linfoma/psicologia , Masculino , Inquéritos e Questionários , Adulto Jovem
11.
Pharmacogenet Genomics ; 23(2): 53-61, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23222202

RESUMO

OBJECTIVES: Methotrexate (MTX) is an important component of therapy for pediatric acute lymphoblastic leukemia (ALL). Treatment with MTX often causes toxicity, which can necessitate dose reduction or treatment cessation. Interindividual differences in adverse reactions can be due to different factors, including polymorphisms in key genes. Recently, we confirmed the association between SLCO1B1 rs11045879 polymorphism and toxicity previously proposed by Treviño and colleagues. As SLCO1B1 is a transporter involved in MTX elimination, other polymorphisms in genes from this pathway could also have a role in MTX toxicity. The aim of the present study was to analyze in depth the role of polymorphisms in the genes of the MTX transport pathway as putative toxicity predictors in pediatric ALL. METHODS: We analyzed 384 single nucleotide polymorphisms in 12 transporter genes (SLCO1B1, SLCO1B3, SLCO1A2, ABCB1, ABCG2, ABCC1, ABCC2, ABCC3, ABCC4, SLC19A1, SLC22A6 and SLC22A8) and their correlation with different toxicity parameters in 151 pediatric ALL patients treated using the LAL/SHOP protocol. RESULTS: A significant association with MTX plasma levels was found for 21 polymorphisms from seven genes and 15 haplotypes. After correction, rs9516519 in ABCC4, rs3740065 in ABCC2, and haplotype GCGGG in ABCC2 remained significantly associated. CONCLUSION: Our results suggest that polymorphisms in ABCC4 and ABCC2 could be novel markers for MTX toxicity in pediatric ALL.


Assuntos
Antimetabólitos Antineoplásicos/efeitos adversos , Biomarcadores Tumorais/genética , Haplótipos/genética , Metotrexato/efeitos adversos , Polimorfismo de Nucleotídeo Único/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Antimetabólitos Antineoplásicos/sangue , Criança , Feminino , Humanos , Masculino , Metotrexato/sangue , Proteína 2 Associada à Farmacorresistência Múltipla , Leucemia-Linfoma Linfoblástico de Células Precursoras/sangue , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Prognóstico , Estudos Retrospectivos
12.
Span. j. psychol ; 16: e1.1-e1.8, 2013. tab
Artigo em Inglês | IBECS | ID: ibc-116230

RESUMO

This research assesses Health-Related Quality of Life (HRQoL) in a Spanish sample of adolescent cancer survivors, and analyzes the relationship between HRQoL, coping styles and physical exercise. Forty-two survivors (12-19 years), who were >= 1 year of remission, completed standardized measures of HRQoL (CHIP-AE), coping strategies (ACS) and physical exercise (AECEF). Mean scores in all HRQoL domains were within normative values. Multiple regression analysis revealed that physical exercise and productive coping were related to higher HRQoL, whereas nonproductive coping was related to lower HRQoL. This sample of survivors reported good levels of HRQoL, which are mediated by coping styles and physical exercise (AU)


No disponible


Assuntos
Humanos , Masculino , Feminino , Criança , Sobrevida , Exercício Físico/psicologia , Comportamento Infantil/psicologia , Qualidade de Vida/psicologia , Psicologia do Adolescente/métodos , Psicologia do Adolescente/organização & administração , Psicologia do Adolescente/normas , Neoplasias/psicologia , Perfil de Impacto da Doença , Modelos Lineares , Modelos Logísticos , Inquéritos e Questionários/normas , Inquéritos e Questionários
13.
J Clin Oncol ; 30(20): 2457-65, 2012 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-22665534

RESUMO

PURPOSE: MMT95 was the fourth of a series of International Society of Pediatric Oncology (SIOP) collaborations for children with high-risk nonmetastatic soft tissue sarcoma (STS). The principal objective was to explore survival advantage for an intensified chemotherapy strategy in a randomized trial. PATIENTS AND METHODS: From July 1995 to June 2003, 457 previously untreated patients with incompletely resected embryonal rhabdomyosarcoma (RMS), undifferentiated sarcoma, and soft tissue primitive neuroectodermal tumor at all sites except paratesticular, vagina, and uterus, or with alveolar RMS were randomly assigned to receive either ifosfamide, vincristine, and dactinomycin (IVA) or a six-drug combination (IVA plus carboplatin, epirubicin, and etoposide) both delivered over 27 weeks. Cumulative doses were as follows: ifosfamide 54 g/m(2) (both arms), epirubicin 450 mg/m(2), etoposide 1,350 mg/m(2) (six-drug regimen). Poor responders after three courses of IVA were to be switched to the other arm. Delivery of radiotherapy was determined according to site and/or response to chemotherapy with or without surgery. RESULTS: Overall survival (OS) for all patients was 81% (95% CI, 77% to 84%) at 3 years. No significant difference in outcome in either OS or event-free survival was noted between the two arms (3-year OS: 82% [95% CI, 76% to 86%] for IVA and 80% [95% CI, 74% to 85%] for the six-drug arm). Toxicity was significantly greater (infection, myelosuppression, and mucositis) in the six-drug arm. Overall burden of local therapy was consistent with data from previous SIOP studies and showed no difference between the two chemotherapy regimens. CONCLUSION: Intensification of chemotherapy for nonmetastatic RMS and other chemotherapy-sensitive STS provides no survival advantage or reduction in the intensity of local therapy and adds toxicity.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Rabdomiossarcoma/tratamento farmacológico , Sarcoma/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carboplatina/administração & dosagem , Criança , Pré-Escolar , Dactinomicina/administração & dosagem , Epirubicina/administração & dosagem , Etoposídeo/administração & dosagem , Feminino , Humanos , Ifosfamida/administração & dosagem , Masculino , Prognóstico , Rabdomiossarcoma/mortalidade , Sarcoma/mortalidade , Resultado do Tratamento , Vincristina/administração & dosagem
14.
Biol Blood Marrow Transplant ; 17(12): 1783-9, 2011 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-21658461

RESUMO

We describe the incidence of malignancy in patients with primary immunodeficiency disorders (PIDD) following hematopoietic cell transplantation (HCT). From the Center for International Blood and Marrow Transplant Research, 2266 PIDD patients who had undergone allogeneic HCT between 1968 and 2003 were identified. Patient, disease, and transplant factors for development of malignancy were examined and pathology reports for reported malignancies reviewed independently by a pathologist for confirmation. The incidence of malignancy was highest for Wiskott-Aldrich syndrome (3.3%), with an overall incidence of 2.3% for PIDD. Post-HCT malignancy was confirmed for 52 of 63 reported cases. Forty-five of 52 patients developed posttransplant lymphoproliferative disorders (PTLD) at a median of 3 months post-HCT. Of these, 26 had received T cell-depleted (TCD) bone marrow. Three patients who developed myelodysplastic syndrome had received TCD marrow and total body irradiation. Three patients developed a solid tumor. Patients with PIDD are at a relatively low risk of developing malignancies post-HCT compared with their historic risk of cancer. The most frequent malignancy or lymphoproliferative disorder was early-onset PTLD. As in other HCT recipients, TCD appears to correlate with PTLD development. Our results lend support to the hypothesis that immune reconstitution in PIDD following HCT leads to a decrease in cancer risk.


Assuntos
Neoplasias Hematológicas/etiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Síndromes de Imunodeficiência/cirurgia , Adolescente , Adulto , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Neoplasias Hematológicas/imunologia , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , Síndromes de Imunodeficiência/imunologia , Lactente , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Transplante Homólogo , Adulto Jovem
15.
J Pediatr Hematol Oncol ; 33(1): e43-5, 2011 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-20829714

RESUMO

Children with Noonan syndrome (NS) are at increased risk of developing juvenile myelomonocytic leukemia (JMML) or a myeloproliferative disorder associated with NS (MPD/NS) resembling JMML in the first weeks of life; whereas JMML is an aggressive disorder requiring hematopoietic stem cell transplantation, MPD/NS may resolve without treatment and cases with spontaneous remission have also been reported. Two cases of NS with hematologic disorders are described. Diagnosis of the syndrome was confirmed by the identification of earlier reported germline missense mutations in the PTPN11 gene. Splenomegaly in 1 patient and leukocytosis, monocytosis and "in vitro" culture assays consistent with JMML in both were the most salient hematologic features. After a 24-month follow-up, these 2 infants continue to improve and JMML has been ruled out. Splenomegaly persists in 1 patient and monocytosis in both, but without signs of malignancy, thereby suggesting abnormal hematopoiesis or MPD/NS, as described in NS.


Assuntos
Transtornos Mieloproliferativos/complicações , Síndrome de Noonan/complicações , Seguimentos , Humanos , Lactente , Recém-Nascido , Leucemia Mielomonocítica Juvenil/genética , Leucemia Mielomonocítica Juvenil/terapia , Masculino , Mutação de Sentido Incorreto , Transtornos Mieloproliferativos/diagnóstico , Transtornos Mieloproliferativos/genética , Transtornos Mieloproliferativos/terapia , Síndrome de Noonan/diagnóstico , Síndrome de Noonan/genética , Proteína Tirosina Fosfatase não Receptora Tipo 11/genética
16.
Haematologica ; 95(6): 936-41, 2010 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-20179088

RESUMO

BACKGROUND: The presence of minimal residual disease detected by polymerase chain reaction techniques prior to allogeneic hematopoietic stem cell transplantation has proven to be an independent prognostic factor for poor outcome in children with acute lymphoblastic leukemia. DESIGN AND METHODS: The aim of this study was to ascertain whether the presence of minimal residual disease detected by multiparametric flow cytometry prior to allogeneic hematopoietic stem cell transplantation is related to outcome in children acute lymphoblastic leukemia. Minimal residual disease was quantified by multiparametric flow cytometry at a median of 10 days prior to hematopoietic stem cell transplantation in 31 children (age range, 10 months to 16 years) with acute lymphoblastic leukemia. Thirteen patients were transplanted in first remission. Stem cell donors were HLA-identical siblings in 8 cases and matched unrelated donors in 23. Twenty-six children received a total body irradiation-containing conditioning regimen. According to the level of minimal residual disease, patients were divided into two groups: minimal residual disease-positive (>or=0.01%) (n=10) and minimal residual disease-negative (<0.01%) (n=21). RESULTS: Estimated event-free survival rates at 2 years for the minimal residual disease-negative and -positive subgroups were 74% and 20%, respectively (P=0.004) and overall survival rates were 80% and 20%, respectively (P=0.005). Bivariate analysis identified pre-transplant minimal residual disease as the only significant factor for relapse and also for death (P<0.01). CONCLUSIONS: The presence of minimal residual disease measured by multiparametric flow cytometry identified a group of patients with a 9.5-fold higher risk of relapse and a 3.2-fold higher risk of death than those without minimal residual disease. This study supports the strong relationship between pre-transplantation minimal residual disease measured by multiparametric flow cytometry and outcome following allogeneic hematopoietic stem cell transplantation and concur with the results of previous studies using polymerase chain reaction techniques.


Assuntos
Citometria de Fluxo/métodos , Transplante de Células-Tronco Hematopoéticas/métodos , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidade , Leucemia-Linfoma Linfoblástico de Células Precursoras/cirurgia , Adolescente , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Lactente , Masculino , Neoplasia Residual , Leucemia-Linfoma Linfoblástico de Células Precursoras/radioterapia , Fatores de Risco , Taxa de Sobrevida/tendências , Transplante Homólogo , Resultado do Tratamento , Irradiação Corporal Total/tendências
17.
Med. clín (Ed. impr.) ; 133(20): 783-786, nov. 2009. tab
Artigo em Espanhol | IBECS | ID: ibc-84215

RESUMO

Fundamento y objetivo: Evaluar la calidad de vida en relación con la salud de un grupo de adolescentes oncológicos en remisión en comparación con adolescentes de la población general sin historia previa de cáncer. Pacientes y método: Se evaluó a un total de 372 adolescentes con edades comprendidas entre los 14 y los 19 años, de los cuales 34 formaban parte del grupo de supervivientes oncológicos y 338 del grupo normativo. A todos ellos se les administró el cuestionario de salud SF-12v2 en una única sesión de evaluación. Resultados: Los adolescentes oncológicos en remisión presentaron puntuaciones medias estadísticamente superiores en comparación con el grupo control en el componente mental (MCS) de calidad de vida del SF-12v2 (52,60 frente a 47,85; p=0,004; intervalo de confianza del 95%: −7,9 a −1,6). No se encontraron diferencias estadísticamente significativas entre ambas muestras en el componente físico (PCS), pese a que los supervivientes presentaron puntuaciones medias superiores (54,03 frente a 52,72). Conclusiones: Los adolescentes supervivientes de cáncer manifiestan una calidad de vida satisfactoria (valores en torno a la media poblacional) y, en concreto, presentan mayor percepción de bienestar psicológico que el grupo control sin historia previa de cáncer (AU)


Background and objective: To assess health-related quality of life of adolescent survivors of childhood cancer, compared to adolescent's health-related quality of life who had no history of cancer. Patients and method: A total of 372 adolescents aged between 14 and 19 years, 34 cancer survivors and a comparison group of 338 peers without a history of cancer, were assessed. All of them filled in the SF-12v2 in a cross-sectional study. Results: Survivors revealed significantly higher mean values compared to the normative group for the Mental Component Scale (MCS) from the SF-12v2 (52,60 vs. 47,85; p=0,004; IC 95%, −7,9–−1,6). No significant differences between groups were found for the Physical Component Scale (PCS), even though adolescent survivors of childhood cancer showed higher mean scores (54,03 vs. 52,72). Conclusions: Adolescent cancer survivors showed a satisfactory quality of life (mean scores around the normative values), and, specifically, they reported greater perception of psychological wellbeing compared to peers (AU)


Assuntos
Humanos , Masculino , Feminino , Adolescente , Adulto , Qualidade de Vida , Neoplasias , Intervalo Livre de Doença , Estudos Transversais , Saúde da Criança , Saúde do Adolescente
18.
Med. clín (Ed. impr.) ; 133(9): 339-343, sept. 2009. tab, graf
Artigo em Espanhol | IBECS | ID: ibc-73268

RESUMO

Fundamento y objetivo: Analizar el perfil clínico del carcinoma diferenciado de tiroides (CDT) y su relación con el pronóstico de la enfermedad. Pacientes y método: Se realizó un análisis retrospectivo de 80 niños con CDT. A todos se les practicó una tiroidectomía total y subtotal. Setenta y cinco niños recibieron dosis de yodo-131. Todos se controlaron anualmente mediante seguimiento clínico, analítico y pruebas de imagen. Resultados: De los 80 pacientes, 52 eran mujeres (edad media de 13,43 y desviación estándar [DE] de 3,6 años). El 87,5% presentó un aumento del diámetro cervical como primer síntoma, que correspondía en un 65% a un nódulo tiroideo y era más frecuente en el sexo femenino. La forma histológica papilar (84%) se presentó más frecuentemente que la folicular y se asoció a mayor presencia de adenopatías y metástasis. El 56,4% de los pacientes presentó enfermedad avanzada en el momento del diagnóstico. Nueve pacientes tenían antecedentes de irradiación previa. Un 32,5% de los pacientes presentó complicaciones posquirúrgicas. Al final del seguimiento (media de 10,79; DE de 5,69 años) sólo 9 pacientes persistían con enfermedad, variable asociada significativamente con el estadio 4. Conclusiones: El CDT en niños se presenta con mayor incidencia en el sexo femenino. La forma de inicio habitual es la presencia de un nódulo cervical. El tipo histológico predominante es el papilar, con elevada frecuencia, en forma de diseminación ganglionar y metastásica (AU)


Background and objective: The objective was to analyze the clinical profile of Differentiated Thyroid Carcinoma in children (DTC) and the predisposing factors to suffering the disease. Material and method: Eighty children with DTC were studied retrospectively. They all underwent total/near total thyroidectomy and 75 cases underwent ablative iodine therapy. Patients were controlled periodically with clinical, laboratory and imaging tests follow-up. Results: Twenty eight patients were male and 52 female (mean age: 13.43±3.6y). The 87.5% of patients had an increased cervical perimeter as the first clinical symptom, 65% of them corresponding to a thyroid nodule with a predominance of females. The papillary histological pattern was more frequent than the follicular pattern, and it was associated with the presence of lymph involvement and metastasis. About 56.4% of patients showed advanced disease at the time of diagnosis. 9 patients had previous irradiation. Surgical complications appeared in 32.5% of patients. At the end of follow-up (mean: 10.79±5.69y) 9 patients had persistent disease with a significant relation with stage 4. Conclusions: DTC presents a higher incidence in females than in males. Cervical node is the most frequent form of initial presentation. The papillary type is more prevalent than the follicular type, and it is frequently associated with lymph node involvement and metastatic spread (AU)


Assuntos
Humanos , Masculino , Feminino , Criança , Carcinoma/diagnóstico , Neoplasias da Glândula Tireoide/diagnóstico , Carcinoma/cirurgia , Neoplasias da Glândula Tireoide/cirurgia , Tireoidectomia , Tireoidectomia/efeitos adversos , Complicações Pós-Operatórias , Estadiamento de Neoplasias
19.
Med Clin (Barc) ; 133(20): 783-6, 2009 Nov 28.
Artigo em Espanhol | MEDLINE | ID: mdl-19592044

RESUMO

BACKGROUND AND OBJECTIVE: To assess health-related quality of life of adolescent survivors of childhood cancer, compared to adolescent's health-related quality of life who had no history of cancer. PATIENTS AND METHOD: A total of 372 adolescents aged between 14 and 19 years, 34 cancer survivors and a comparison group of 338 peers without a history of cancer, were assessed. All of them filled in the SF-12v(2) in a cross-sectional study. RESULTS: Survivors revealed significantly higher mean values compared to the normative group for the Mental Component Scale (MCS) from the SF-12v(2) (52,60 vs. 47,85; p=0,004; IC 95%, -7,9--1,6). No significant differences between groups were found for the Physical Component Scale (PCS), even though adolescent survivors of childhood cancer showed higher mean scores (54,03 vs. 52,72). CONCLUSIONS: Adolescent cancer survivors showed a satisfactory quality of life (mean scores around the normative values), and, specifically, they reported greater perception of psychological wellbeing compared to peers.


Assuntos
Neoplasias , Qualidade de Vida , Sobreviventes , Adolescente , Estudos Transversais , Feminino , Humanos , Masculino , Adulto Jovem
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