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1.
Support Care Cancer ; 27(12): 4389-4391, 2019 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-31511982

RESUMEN

BACKGROUND: Currently the entire treatment of a child with cancer is carried out in a specialized hospital. It would be ideal to conduct part of the treatment at home. This can only be done with adequately trained personnel. In the Netherlands, specialized pediatric oncology home care nurse practitioners have been trained to deliver this kind of care. Therefore, a pilot study was conducted to administer intravenous chemotherapy at home. PURPOSE: This study aimed to safely administer chemotherapy intravenously (iv) at home by specialized nurse practitioners and aimed to increase the quality of life (QOL) of the child and decrease the social burden in families with a child with acute lymphoblastic leukemia (ALL). METHOD: The pilot study was performed by well-trained home care nurse practitioners. Low-dose methotrexate iv and low-dose cytarabine iv were administered to 11 included children with ALL in their home environment. RESULTS: QOL increased whereas social burden decreased for patients and parents. Chemotherapy administration in the home environment was safe with the help of well-trained nurse practitioners. CONCLUSION: It is feasible to administer intravenous chemotherapy at home in a safe and efficient way. The role of the specialized pediatric oncology nurse practitioner is an essential one.


Asunto(s)
Antimetabolitos Antineoplásicos/administración & dosificación , Servicios de Atención de Salud a Domicilio/organización & administración , Enfermeras Practicantes , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/enfermería , Administración Intravenosa , Antimetabolitos Antineoplásicos/efectos adversos , Niño , Preescolar , Citarabina/administración & dosificación , Citarabina/efectos adversos , Femenino , Servicios de Atención de Salud a Domicilio/normas , Humanos , Masculino , Metotrexato/administración & dosificación , Metotrexato/efectos adversos , Países Bajos , Proyectos Piloto , Calidad de Vida
2.
Hum Reprod ; 32(12): 2366-2372, 2017 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-29040511

RESUMEN

STUDY QUESTION: Is testicular growth affected by a testicular biopsy intended for fertility preservation in pre-pubertal boys with cancer? SUMMARY ANSWER: Testicular growth of the biopsied testis is not impeded in comparison to the non-biopsied contralateral testis up until 1 year after surgery. WHAT IS KNOWN ALREADY: Fertility preservation in pre-pubertal boys by means of testicular biopsy has been conducted for more than 15 years. Although immediate adverse effects of testicular biopsy are rare (1%), no data exist on the effect of biopsy on testicular growth. STUDY DESIGN, SIZE, DURATION: In this prospective cohort study, between March 2011 and February 2017, 93 parents of pre-pubertal boys were offered cryopreservation of testicular tissue of their son, of whom 78 consented. Sixty-four boys were included in this follow-up study. PARTICIPANTS/MATERIALS, SETTING, METHODS: All boys with cancer at the paediatric oncology department of the Academic Medical Center (AMC) who needed gonadotoxic therapy and were unable to ejaculate were offered cryopreservation of testicular tissue prior to treatment. By testicular ultrasound before and after biopsy (1, 6 and 12 months after biopsy), volume and parenchymal abnormalities were assessed. Data were analysed using mixed-effects modelling. MAIN RESULTS AND THE ROLE OF CHANCE: Of the 64 included boys all were followed up at 1 month, 58 at 6 months and 55 at 12 months. Mean testicular volumes after 1, 6 and 12 months after biopsy were 1.7 ± 2.1, 1.7 ± 2.2 and 1.9 ± 2.4 for the biopsied testis and 1.8 ± 2.2, 1.8 ± 2.3 and 2.0 ± 2.2 for the non-biopsied testis, respectively. Biopsy of the testis did not have a significant impact on testicular growth. Immediate adverse effects of the biopsy, i.e. wound infections, were seen in 3/78 boys (3.8%). LIMITATIONS, REASONS FOR CAUTION: Although it is the largest cohort available to date, the number of patients included in our follow-up is still relatively small. A larger cohort would be able to evaluate growth more precisely. Follow-up was discontinued in a significant portion of boys, 12/76 (15.8%), mainly because of death due to primary illness but also because they could not be reached or declined further follow-up. WIDER IMPLICATIONS OF THE FINDINGS: These reassuring data may be used in counselling future boys who are eligible for fertility preservation and their parents. STUDY FUNDING/COMPETING INTEREST(S): Study funded by KIKA Foundation (Kika 86), Grant from the Netherlands Organisation for Health Research and Development (ZonMW TAS-116003002). The authors declare no conflict of interest. TRIAL REGISTRATION NUMBER: CCMO-register: NL27690.000.09.


Asunto(s)
Biopsia/efectos adversos , Preservación de la Fertilidad/métodos , Neoplasias/terapia , Testículo/crecimiento & desarrollo , Testículo/patología , Adolescente , Niño , Preescolar , Criopreservación , Humanos , Lactante , Masculino , Neoplasias/complicaciones , Países Bajos , Estudios Prospectivos , Factores de Tiempo
3.
Support Care Cancer ; 25(10): 3151-3160, 2017 10.
Artículo en Inglés | MEDLINE | ID: mdl-28456909

RESUMEN

PURPOSE: Intensive therapies in pediatric malignancies increased survival rates but also occurrence of treatment-related morbidities. Therefore, supportive care fulfills an increasingly important role. In planning development of guidelines with incorporation of shared decision making, we noticed that little is known about the needs and preferences of patients and their parents. Our goals were therefore to investigate (1) which supportive care topics patients and parents regard as most important and (2) the preferred role they wish to fulfill in decision making. METHODS: This qualitative study consisted of three focus groups (two traditional, one online) with patients and parents of two Dutch pediatric oncology centers. Data were transcribed as simple verbatim and analyzed using thematic analysis. RESULTS: Eleven adolescent patients and 18 parents shared detailed views on various aspects of supportive care. Themes of major importance were communication between patient and physician (commitment, accessibility, proactive attitude of physicians), well-timed provision of information, and the suitability and accessibility of psychosocial care. In contrast to prioritized supportive care topics by medical professionals, somatic issues (e.g., febrile neutropenia) were infrequently addressed. Patients and parents preferred to be actively involved in decision making in selected topics, such as choice of analgesics and anti-emetics, but not in, e.g., choice of antibiotics. CONCLUSIONS: Children with cancer and parents were provided a valuable insight into their views regarding supportive care and shared decision making. These results have important implications towards improving supportive care, both in selecting topics for guideline development and incorporating preferences of patients and parents herein.


Asunto(s)
Actitud , Neoplasias/psicología , Neoplasias/terapia , Padres/psicología , Percepción , Sistemas de Apoyo Psicosocial , Adolescente , Adulto , Niño , Conducta de Elección , Toma de Decisiones , Femenino , Grupos Focales , Humanos , Masculino , Persona de Mediana Edad , Cuidados Paliativos/métodos , Cuidados Paliativos/psicología , Participación del Paciente/psicología , Participación del Paciente/estadística & datos numéricos , Relaciones Médico-Paciente , Relaciones Profesional-Familia
4.
Support Care Cancer ; 25(4): 1121-1125, 2017 04.
Artículo en Inglés | MEDLINE | ID: mdl-27928642

RESUMEN

As cure rates in pediatric oncology have improved substantially over the last decades, supportive care has become increasingly important to reduce morbidity and mortality and improve quality of life in children with cancer. Currently, large variations exist in pediatric oncology supportive care practice, which might negatively influence care. This plea underlines the importance of development and implementation of trustworthy supportive care clinical practice guidelines, which we believe is the essential next step towards better supportive care practice, and thus a higher quality of care. To facilitate international development and endorsement, the International Pediatric Oncology Guidelines in Supportive Care Network has been established.


Asunto(s)
Oncología Médica/normas , Neoplasias/terapia , Cuidados Paliativos/normas , Pediatría/normas , Guías de Práctica Clínica como Asunto , Niño , Práctica Clínica Basada en la Evidencia , Humanos , Cuidados Paliativos/métodos , Calidad de Vida
5.
Artículo en Inglés | MEDLINE | ID: mdl-28370728

RESUMEN

In order to gain more insight on the influence of ethnic diversity in paediatric cancer care, the perspectives of care providers were explored. Semi-structured interviews were conducted among 12 paediatric oncologists and 13 nurses of two different paediatric oncology wards and were analysed using a framework method. We found that care providers described the contact with Turkish and Moroccan parents as more difficult. They offered two reasons for this: (1) language barriers between care provider and parents hindered the exchange of information; (2) cultural barriers between care provider and parents about sharing the diagnosis and palliative perspective hindered communication. Care providers reported different solutions to deal with these barriers, such as using an interpreter and improving their cultural knowledge about their patients. They, however, were not using interpreters sufficiently and were unaware of the importance of eliciting parents' perspectives. Communication techniques to overcome dilemmas between parents and care providers were not used and care providers were unaware of stereotypes and prejudice. Care providers should be offered insight in cultural barriers they are unaware of. Training in cultural competence might be a possibility to overcome manifest barriers.


Asunto(s)
Actitud del Personal de Salud , Barreras de Comunicación , Asistencia Sanitaria Culturalmente Competente , Emigrantes e Inmigrantes , Neoplasias/terapia , Enfermeras Pediátricas , Oncólogos , Competencia Cultural , Revelación , Humanos , Marruecos/etnología , Países Bajos , Enfermería Oncológica , Cuidados Paliativos , Pediatría , Investigación Cualitativa , Turquía/etnología
6.
Infect Prev Pract ; 6(2): 100352, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38510847

RESUMEN

Background: Taurolidine containing lock solutions (TL) are a promising method for the prevention of central line associated bloodstream infections. Per accident, the TL may not always be aspirated from the central venous catheter (CVC) before blood cultures are obtained. The TL could, unintentionally, end up in a blood culture vial, possibly altering the results. The aim of this study was to investigate the effect of the TLs on the detection of microbial growth in blood culture vials. Methods: Different lock solutions (taurolidine-citrate-heparin (TCHL), taurolidine, heparin, citrate or NaCl) were added to BD BACTECTM blood culture vials (Plus Aerobic/F, Lytic/10 Anaerobic/F or Peds Plus/F) before spiking with Staphylococcus aureus (ATCC 29213 or a clinical strain) or Escherichia coli (ATCC 25922 or a clinical strain) in the presence and absence of blood. Subsequently, blood culture vials were incubated in the BD BACTEC FX instrument with Time-to-positivity (TTP) as primary outcome. In addition, the effect of the TCHL on a variety of other micro-organisms was tested. Discussion: In the presence of taurolidine, the TTP was considerably delayed or vials even remained negative as compared to vials containing heparin, citrate or NaCl. This effect was dose-dependent. The delayed TTP was much less pronounced in the presence of blood, but still notable. Conclusion: This study stresses the clinical importance of discarding TLs from the CVC before obtaining a blood culture.

7.
J Pediatr Surg ; 2024 Jan 06.
Artículo en Inglés | MEDLINE | ID: mdl-38212153

RESUMEN

BACKGROUND: To compare paediatric oncologic vascular access ports located on the anterior thoracic wall to ports on the lower lateral thoracic wall, in terms of perceived port-related hindrance and scar-quality. METHODS: A cross-sectional survey study including paediatric oncology patients (≥8-<19 yrs), caregivers (in patients <8 yrs), survivors (>22 yrs with only anterior ports) and nurses of the Princess Máxima Center, the Netherlands, was performed. The survey consisted of questions regarding satisfaction, hindrance during daily life, and port position preference. For survivors, scar-quality was assessed using the validated Patient and Observer Scar Assessment Scale (POSAS 2.0); a high score (i.e., a displeasing scar) was defined as a score higher than the third quartile of the median for that question. RESULTS: In total, 147 participants were included; 83 patients/caregivers, 31 survivors, and 33 nurses. Overall, 81 % was satisfied with the position of their port. Satisfaction, hindrance and complications did not differ between anterior and lower lateral ports. For the anterior position, minimal pressure on the port during daily life was a mentioned reason to prefer this position. For the lower lateral position, less visibility of the scar and easiest access were mentioned. Of all survivors with an anterior port scar, one in five had a displeasing scar and all scars observed were widened. Female patients preferred a lower lateral port, and scar-quality was better for left-sided port scars. CONCLUSION: The port position should be chosen together with patients/caregivers based on the (dis-)advantages of each position, as identified by this study. LEVEL OF EVIDENCE: II.

8.
Support Care Cancer ; 20(12): 3149-53, 2012 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-22476398

RESUMEN

PURPOSE: Treatment protocols in pediatric oncology have historically known high accrual rates, up to 94 %. Accrual for supportive care studies on the other hand appears to be a challenge. The aim of this study was to search for reasons explaining this poor accrual and for possible interventions to improve patient enrolment. METHODS: The failure screen log of our supportive care study (the Aristocaths study) was analyzed, and subsequently, a literature search was performed. RESULTS: The literature search (1985-2011) revealed three factors that can influence accrual. Firstly, study implementation and patient enrolment can be facilitated by appointing a dedicated clinical investigator in all participating centers and by facilitating clinical research nurses. Furthermore, adequate and tailor-made information is required for families to make a well-informed decision regarding study participation. Lastly, sufficient time should be assured for the process of decision making, especially since the number of eligible studies is increasing rapidly. Concerning our study, all three elements were met, but the most striking finding was the presumed burden of study participation by the majority of parents (82 %) as the main argument against randomization. CONCLUSIONS: Accrual of pediatric oncology patients in supportive care studies is challenging. Nevertheless, well-designed randomized controlled trials in supportive care will be essential for the improvement of pediatric cancer care. Therefore, we will need to increase awareness through (inter)national supportive care working groups regarding the need for supportive care trials and stimulate accrual when such trials are open.


Asunto(s)
Ensayos Clínicos como Asunto , Neoplasias/terapia , Selección de Paciente , Actitud del Personal de Salud , Niño , Conocimientos, Actitudes y Práctica en Salud , Humanos
9.
J Hosp Infect ; 123: 143-155, 2022 May.
Artículo en Inglés | MEDLINE | ID: mdl-34767871

RESUMEN

The incidence of central venous catheter (CVC)-related bloodstream infections is high in patients requiring a long-term CVC. Therefore, infection prevention is of the utmost importance. The aim of this study was to provide an updated overview of randomized controlled trials (RCTs) comparing the efficacy of taurolidine containing lock solutions (TL) to other lock solutions for the prevention of CVC-related bloodstream infections in all patient populations. On 15th February 2021, PubMed, Embase and The Cochrane Library were searched for RCTs comparing the efficacy of TLs for the prevention of CVC-related bloodstream infections with other lock solutions. Exclusion criteria were non-RCTs, studies describing <10 patients and studies using TLs as treatment. Risk of bias was evaluated using the Cochrane Risk of Bias 2 tool. A random effects model was used to pool individual study incidence rate ratios (IRRs). Subgroup analyses were performed based on the following factors: CVC indication, comparator lock and bacterial isolates cultured. A total of 14 articles were included in the qualitative synthesis describing 1219 haemodialysis, total parenteral nutrition and oncology patients. The pooled IRR estimated for all patient groups together (nine studies; 918 patients) was 0.30 (95% confidence interval 0.19-0.46), favouring the TLs. Adverse events (10 studies; 867 patients) were mild and scarce. The quality of the evidence was limited due to a high risk of bias and indirectness of evidence. The use of TLs might be promising for the prevention of CVC-related bloodstream infections. Large-scale RCTs are needed to draw firm conclusions on the efficacy of TLs.


Asunto(s)
Infecciones Relacionadas con Catéteres , Cateterismo Venoso Central , Catéteres Venosos Centrales , Sepsis , Tiadiazinas , Infecciones Relacionadas con Catéteres/epidemiología , Infecciones Relacionadas con Catéteres/microbiología , Infecciones Relacionadas con Catéteres/prevención & control , Cateterismo Venoso Central/efectos adversos , Catéteres Venosos Centrales/efectos adversos , Humanos , Ensayos Clínicos Controlados Aleatorios como Asunto , Sepsis/etiología , Taurina/análogos & derivados , Tiadiazinas/uso terapéutico
10.
Clin Exp Immunol ; 165(1): 51-9, 2011 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-21488869

RESUMEN

Deficiency of mannose-binding lectin (MBL) has been suggested to influence duration of febrile neutropenia and prognosis in paediatric oncology patients. However, there is no consensus on the definition of MBL deficiency. In a cohort of children with cancer, we investigated (i) how to determine MBL deficiency and (ii) whether MBL is a prognostic factor for disease severity. In 222 paediatric oncology patients, 92 healthy children and 194 healthy adults, MBL plasma levels and MBL2 genotype (wild-type: A, variant: O) were determined. Event-free survival (EFS), overall survival (OS) and paediatric intensive care unit (PICU) admissions were recorded prospectively. In febrile neutropenic patients admitted to the PICU, disease severity was assessed by clinical, microbiological and laboratory parameters. An optimal cut-off value for MBL deficiency was determined to be < 0·20 µg/ml. Wild-type MBL2 genotype patients, including the XA/XA haplotype, had increased MBL levels compared to healthy individuals. MBL deficiency was associated with decreased EFS (P = 0·03), but not with need for PICU admission. A trend for a twice increased frequency of septic shock (80% versus 38%, P = 0·14), multiple organ failure (40% versus 17%, P = 0·27) and death (40% versus 21%, P = 0·27) was observed in the absence of microbiological findings. MBL deficiency was associated with decreased EFS and possibly with an increased severity of disease during PICU admission after febrile neutropenia in the absence of any association with microbiological findings. These findings suggest prognosis to be worse in MBL-deficient compared to MBL-sufficient paediatric oncology patients.


Asunto(s)
Neoplasias Hematológicas/diagnóstico , Neoplasias Hematológicas/genética , Lectina de Unión a Manosa/genética , Lectina de Unión a Manosa/inmunología , Adulto , Niño , Preescolar , Progresión de la Enfermedad , Servicios Médicos de Urgencia , Predisposición Genética a la Enfermedad , Neoplasias Hematológicas/mortalidad , Neoplasias Hematológicas/fisiopatología , Humanos , Lactante , Recién Nacido , Masculino , Lectina de Unión a Manosa/sangre , Neutropenia , Servicio de Oncología en Hospital , Polimorfismo Genético , Pronóstico , Índice de Severidad de la Enfermedad , Análisis de Supervivencia
11.
Pediatr Blood Cancer ; 57(1): 89-96, 2011 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-21557458

RESUMEN

BACKGROUND: We determined whether mannose-binding lectin (MBL) deficiency is associated with an increased risk of febrile neutropenia (FN) and/or infection in pediatric oncology patients. PROCEDURE: We systematically searched and reviewed all the literature on MBL and infections in children with cancer, identified from a literature search of Medline, Embase, and Central (1966-April 2010). We extracted information on the type of study, patient characteristics, definition of MBL deficiency, definition of infection and method of detection, follow-up period and the results of the outcome in different groups. The validity of each study was assessed. RESULTS: Six cohort studies were retrieved, consisting of 581 children with leukemia (n = 2) or varying types of cancer (n = 4). Many different outcome definitions were used. In only one out of three genotype studies, variant MBL2 genotypes, as well as MBL levels < 1,000 µg/L, were associated with an increased duration of FN. In one additional MBL level study the number of FN episodes, bacteremia and severe bacterial infection were increased in patients with MBL levels < 100 µg/L as compared to those with MBL levels of 100-999 µg/L. Sepsis, pneumonia, viral infection, and fungal infection were not associated with either MBL levels or genotypes in any of the studies. CONCLUSIONS: MBL deficiency could not be identified as an independent risk factor for FN or infection in pediatric oncology patients. A multicenter study of children with comparable chemotherapy regimens, relevant and equal outcome definitions and measuring both MBL levels and genotypes, will be required to avoid clinical and methodological inconsistencies.


Asunto(s)
Bacteriemia/sangre , Lectina de Unión a Manosa/sangre , Micosis/sangre , Neoplasias/tratamiento farmacológico , Neutropenia/sangre , Virosis/sangre , Adolescente , Bacteriemia/inducido químicamente , Bacteriemia/genética , Niño , Preescolar , Femenino , Genotipo , Humanos , MEDLINE , Masculino , Lectina de Unión a Manosa/genética , Micosis/inducido químicamente , Micosis/genética , Neoplasias/sangre , Neoplasias/genética , Neutropenia/inducido químicamente , Factores de Riesgo , Virosis/inducido químicamente , Virosis/genética
12.
Pediatr Blood Cancer ; 56(4): 646-53, 2011 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-21298753

RESUMEN

BACKGROUND: Previous studies have assessed health-related quality of life (HRQOL) during several treatment stages in children with cancer, but there is limited knowledge about HRQOL shortly after completing therapy. This study determined HRQOL of children with cancer shortly after the end of successful treatment compared with normative values. PROCEDURE: Several age-specific HRQOL questionnaires were administered: the ITQOL (generic, proxy-report, 0-4 years), CHQ PF 50 (generic, proxy-report, 5-7 years), Kidscreen (generic, self-report, 8-18 years) and Disabkids (chronic generic, self-report, 8-18 years). RESULTS: Children with cancer (N = 191, mean age 9.25, SD 5.06, 47.1% female) participated. Physical well-being was affected for all ages. Compared to normative values 0- to 7-year-olds were rated significantly lower on the majority of the scales. In addition, 12- to 18-year-olds had significantly better HRQOL than the norm on social scales. Compared to chronically ill norms, 8- to 18-year-olds demonstrated no differences, except for 12- to 18-year-olds who experienced significantly more physical limitations. Additionally, we found that HRQOL of parents of 0- to 7-year-olds was poorer than the norm. CONCLUSION: HRQOL in children with cancer and their parents can be impaired compared with the norm. Therefore, HRQOL should be monitored in clinical practice to make paediatric oncologists aware of these problems. For young children, we recommend checking whether certain HRQOL problems can be explained by parental worries. For older children and adolescents, paediatric oncologists need to consider social desirability and the child's adaptive style.


Asunto(s)
Estado de Salud , Neoplasias/terapia , Calidad de Vida , Adolescente , Niño , Conducta Infantil , Preescolar , Femenino , Humanos , Lactante , Masculino , Encuestas y Cuestionarios
13.
Pediatr Hematol Oncol ; 28(1): 71-7, 2011 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-21083354

RESUMEN

Gastric adenocarcinoma is not uncommon in the adult population, but in the pediatric population it is an extremely rare entity. A 13-year-old boy was referred to a pediatric oncology unit for evaluation of a tumor in the upper abdomen. Further investigation revealed an advanced stage gastric carcinoma with metastases suggestive for a hereditary cause. Awareness for uncommon diagnoses is a key issue in regard of accurate treatment and overall prognosis.


Asunto(s)
Adenocarcinoma/diagnóstico , Neoplasias Gástricas/diagnóstico , Adenocarcinoma/tratamiento farmacológico , Adolescente , Distribución por Edad , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Humanos , Masculino , Pronóstico , Neoplasias Gástricas/tratamiento farmacológico , Tomografía Computarizada por Rayos X
14.
J Exp Med ; 173(5): 1133-42, 1991 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-1827138

RESUMEN

CD3-epsilon gene expression is confined to the T cell lineage. We have recently identified and cloned a human transcription factor, TCF-1, that binds to a functional element in the T lymphocyte-specific enhancer of CD3-epsilon. In a panel of human cell lines, TCF-1 expression was restricted to T lineage cells. TCF-1 belonged to a novel family of genes that contain the so-called high mobility group 1 (HMG) box. Here we report the cloning of murine TCF-1. Two splice alternatives were identified that were not previously observed in human TCF-1. Murine and human TCF-1 displayed a 95.5% overall amino acid homology. Recombinant murine and human TCF-1 recognized the same sequence motif in the CD3-epsilon enhancer as judged by gel retardation and methylation interference assays. With the murine cDNA clones several aspects of TCF-1 were analyzed. First, deletion analysis revealed that a region of TCF-1 containing the HMG box was sufficient for sequence-specific binding. Second, by high stringency Northern blotting and in situ hybridization, TCF-1 expression was shown to be confined to the thymus and to the T cell areas of the spleen. Third, TCF-1 bound specifically to a functional T cell-specific element in the T cell receptor alpha (TCR-alpha) enhancer. The T lineage-specific expression and the affinity for functional motifs in the TCR-alpha and CD3-epsilon enhancers imply an important role for TCF-1 in the establishment of the mature T cell phenotype.


Asunto(s)
Antígenos de Diferenciación de Linfocitos T/fisiología , Elementos de Facilitación Genéticos/fisiología , Receptores de Antígenos de Linfocitos T/fisiología , Factores de Transcripción/genética , Secuencia de Aminoácidos , Animales , Antígenos de Diferenciación de Linfocitos T/genética , Antígenos de Diferenciación de Linfocitos T/metabolismo , Linfocitos B/metabolismo , Linfocitos B/ultraestructura , Secuencia de Bases , Northern Blotting , Complejo CD3 , Línea Celular , Deleción Cromosómica , ADN/genética , ADN/aislamiento & purificación , Elementos de Facilitación Genéticos/genética , Expresión Génica , Humanos , Ratones , Datos de Secuencia Molecular , Receptores de Antígenos de Linfocitos T/genética , Receptores de Antígenos de Linfocitos T/metabolismo , Recombinación Genética , Homología de Secuencia de Ácido Nucleico , Linfocitos T/metabolismo , Linfocitos T/ultraestructura , Factores de Transcripción/metabolismo , Factores de Transcripción/fisiología
15.
Mol Immunol ; 93: 189-192, 2018 01.
Artículo en Inglés | MEDLINE | ID: mdl-29197742

RESUMEN

Oncological treatment has been associated with an increased risk of infection, most often related to therapy-induced pancytopenia. However, limited research has been conducted on the effect of oncological therapy on the complement system, being part of the non-cellular innate immune system. This became the rationale for an observational clinical study (C2012) in which we have investigated the prevalence of transient complement defects. Once we had observed such defects, a correlation of the complement defects to specific clinical parameters or to specific therapeutic regimens was investigated. A prominent defect observed in C2012 was the inhibition of the lectin pathway (LP) of complement activation during the treatment of acute lymphoblastic leukemia (ALL), which we could directly associate to the use of asparaginase (ASNase). Ex-vivo experiments confirmed a direct dose-dependent inhibitory effect of ASNase on the LP functionality.


Asunto(s)
Asparaginasa/farmacología , Lectina de Unión a Manosa de la Vía del Complemento/efectos de los fármacos , Polietilenglicoles/farmacología , Asparaginasa/administración & dosificación , Asparaginasa/uso terapéutico , Niño , Depresión Química , Relación Dosis-Respuesta a Droga , Humanos , Lectina de Unión a Manosa/sangre , Serina Proteasas Asociadas a la Proteína de Unión a la Manosa/antagonistas & inhibidores , Polietilenglicoles/administración & dosificación , Polietilenglicoles/uso terapéutico , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Unión Proteica/efectos de los fármacos
16.
Curr Biol ; 9(2): 105-8, 1999 Jan 28.
Artículo en Inglés | MEDLINE | ID: mdl-10021369

RESUMEN

The adenomatous polyposis coli (APC) tumour-suppressor protein controls the Wnt signalling pathway by forming a complex with glycogen synthase kinase 3beta (GSK-3beta), axin/conductin and betacatenin. Complex formation induces the rapid degradation of betacatenin. In colon carcinoma cells, loss of APC leads to the accumulation of betacatenin in the nucleus, where it binds to and activates the Tcf-4 transcription factor (reviewed in [1] [2]). Here, we report the identification and genomic structure of APC homologues. Mammalian APC2, which closely resembles APC in overall domain structure, was functionally analyzed and shown to contain two SAMP domains, both of which are required for binding to conductin. Like APC, APC2 regulates the formation of active betacatenin-Tcf complexes, as demonstrated using transient transcriptional activation assays in APC -/- colon carcinoma cells. Human APC2 maps to chromosome 19p13.3. APC and APC2 may therefore have comparable functions in development and cancer.


Asunto(s)
Poliposis Adenomatosa del Colon/genética , Proteínas del Citoesqueleto/genética , Genes APC , Neuropéptidos/genética , Serina Endopeptidasas/genética , Secuencia de Aminoácidos , Animales , Proteínas del Citoesqueleto/química , Humanos , Ratones , Datos de Secuencia Molecular , Neuropéptidos/química , Homología de Secuencia de Aminoácido , Serina Endopeptidasas/química
17.
Trends Genet ; 13(12): 485-9, 1997 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-9433138

RESUMEN

Factors of the TCF/LEF HMG domain family (TCFs) exist in vertebrates, Drosophila melanogaster and Caenorhabditis elegans. It has very recently become evident that TCFs interact with the vertebrate WNT effector beta-catenin to mediate axis formation in Xenopus. Likewise, Armadillo (the Drosophila ortholog of beta-catenin) is genetically upstream of a Drosophila TCF in the Wingless pathway. Upon Wingless/Wnt signaling, Armadillo/beta-catenin associate with nuclear TCFs and contribute a trans-activation domain to the resulting bipartite transcription factor. The cytoplasmic tumor-suppressor protein APC binds to beta-catenin causing its destruction. In APC-deficient colon carcinoma cells, beta-catenin accumulates and is constitutively complexed with TCF factors. In APC-positive colon carcinomas and melanomas, dominant mutations in beta-catenin render it indestructable, providing an alternative mechanism to activate transcription of TCF target genes inappropriately. So, transcriptional activation of TCF target genes by beta-catenin appears to be a central event in development and cellular transformation.


Asunto(s)
Neoplasias del Colon/genética , Proteínas del Citoesqueleto/genética , Proteínas de Unión al ADN/fisiología , Proteínas de Drosophila , Regulación del Desarrollo de la Expresión Génica , Transactivadores , Factores de Transcripción/fisiología , Animales , Proteínas del Dominio Armadillo , Sitios de Unión , Proteínas del Citoesqueleto/metabolismo , Proteínas de Unión al ADN/química , Drosophila/genética , Drosophila/crecimiento & desarrollo , Humanos , Proteínas de Insectos/genética , Proteínas de Insectos/metabolismo , Factor de Unión 1 al Potenciador Linfoide , Mamíferos/crecimiento & desarrollo , Factores de Transcripción/química , Xenopus/genética , Xenopus/crecimiento & desarrollo , Proteínas de Xenopus , beta Catenina
18.
Eur J Cancer ; 43(14): 2082-92, 2007 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-17761413

RESUMEN

BACKGROUND: Granulocyte transfusions (GTX) have been used for decades in paediatric neutropaenic patients, but uncertainty remains regarding their effectiveness. We reviewed all the paediatric data available on GTX, to gain a insight in to the indications for use, favourable effects and side effects in patients and donors. METHODS: A comprehensive search was done in MEDLINE, EMBASE, LILACS and CENTRAL (1966 until 2006). All studies including children (1-18 years) who received GTX were included. RESULTS: A total of 66 observational studies were included:Seven using prophylactic and 59 therapeutic GTX. Of the therapeutic studies 55 reported a proven sepsis caused by Gram-negative bacteria (34%) or fungal disease (48%) as the indication for GTX. Concerning effectiveness 70% survival was reported, but no controlled studies were identified. Side effects were mentioned in 27 studies including mild respiratory symptoms, allergic reactions and infection related complications (CMV). Side effects in the donor were mainly flu-like illness. DISCUSSION: In this first review covering 30 years of experience on the use of GTX in children, we found no randomised evidence showing a positive benefit risk ratio. The available case reports and cohort studies alert us as to the potential benefits and harms of the use of GTX in neutropaenic children and provides the basis for a well designed trial in children.


Asunto(s)
Granulocitos/trasplante , Transfusión de Leucocitos/métodos , Neutropenia/terapia , Adolescente , Niño , Preescolar , Métodos Epidemiológicos , Neoplasias Hematológicas/terapia , Humanos , Enfermedades del Sistema Inmune/terapia , Lactante , Infecciones/terapia
19.
Mol Cell Biol ; 16(3): 745-52, 1996 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-8622675

RESUMEN

Previously, we reported the isolation of cDNA clones representing four alternative splice forms of TCF-1, a T-cell-specific transcription factor. In the present study, Western blotting (immunoblotting) yielded a multitude of TCF-1 proteins ranging from 25-55 kDa, a pattern not simply explained from the known splice alternatives. Subsequent cDNA cloning, PCR amplification, and analysis by rapid amplification of 5' cDNA ends revealed (i) the presence of an alternative upstream promoter, which extended the known N terminus by 116 amino acids, (ii) the presence of four alternative exons, and (iii) the existence of a second reading frame in the last exon encoding an extended C terminus. Inclusion of the extended N terminus into the originally reported protein resulted in a striking similarity to the lymphoid factor Lef-1. Several of the TCF-1 isoforms, although less potent, mimicked Lef-1 in transactivating transcription through the T-cell receptor alpha-chain (TCR-alpha) enhancer. These data provide a molecular basis for the complexity of the expressed TCF-1 proteins and establish the existence of functional differences between these isoforms. Furthermore, the functional redundancy between Tcf-1 and Lef-1 explains the apparently normal TCR-alpha expression in single Tcf-1 or Lef-1 knockout mice despite the firm in vitro evidence for the importance of the Tcf/Lef site in the TCR-alpha enhancer.


Asunto(s)
Proteínas de Unión al ADN/genética , Factores de Transcripción/genética , Empalme Alternativo , Secuencia de Aminoácidos , Animales , Secuencia de Bases , Línea Celular , Clonación Molecular , ADN Complementario/genética , ADN Complementario/aislamiento & purificación , Proteínas de Unión al ADN/metabolismo , Técnicas de Transferencia de Gen , Factor Nuclear 1-alfa del Hepatocito , Factor de Unión 1 al Potenciador Linfoide , Ratones , Datos de Secuencia Molecular , Regiones Promotoras Genéticas/genética , Alineación de Secuencia , Factor 1 de Transcripción de Linfocitos T , Factores de Transcripción/metabolismo , Transcripción Genética
20.
Cochrane Database Syst Rev ; (1): CD003295, 2007 Jan 24.
Artículo en Inglés | MEDLINE | ID: mdl-17253487

RESUMEN

BACKGROUND: Long-term tunnelled central venous catheters (TCVCs) are increasingly used when treating oncology patients. Despite international guidelines on sterile insertion, appropriate catheter maintenance and use, infections still a complication of TCVC. These infections are mainly caused by Gram-positive bacteria. Antimicrobial prevention strategies aimed at these micro-organisms could potentially decrease the majority of TCVC infections. The aim of this review was to evaluate the efficacy of antibiotics in the prevention of early TCVC infections. OBJECTIVES: To determine the efficacy of administering antibiotics prior to insertion of a TCVC with or without vancomycin/heparin flush technique in the first 45 days after insertion of the catheter to prevent Gram-positive catheter-related infections in oncology patients. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) to July 2006. MEDLINE (1966 to 2006) and EMBASE (1966 to 2006). Reference lists from relevant articles were scanned and conference proceedings were hand searched. The authors of eligible studies were contacted to obtain additional information. SELECTION CRITERIA: We selected RCTs which administered prophylactic antibiotics prior to insertion of the TCVC, and RCTs using the combination of an antibiotic and heparin to flush the CVC in oncology patients (both adults and children). DATA COLLECTION AND ANALYSIS: The studies identified were assessed and the data extracted independently by the two authors. Authors were contacted for details of randomization, and a quality assessment was carried out. The analysis was carried out using the standard Cochrane software package, RevMan 4.2. MAIN RESULTS: We included nine trials with a total of 588 patients. Four reported on vancomycin/teicoplanin prior to insertion of the TCVC compared to placebo, and five trials reported on antibiotic flushing combined with heparin, compared to heparin flushing only. The overall effect of administering an antibiotic prior to insertion of the catheter decreases the number of Gram positive TCVC infections (odds ratio [OR] = 0.42, 95% confidence interval (CI) 0.13 to 1.31), this effect is not significant. Flushing the TCVC with antibiotics and heparin proved to be beneficial (OR = 0.43, 95% CI 0.21 to 0.87). For intraluminal colonization the baseline infection rate is 15% which leads to a number needed to treat (NNT) of 13 (95 % CI 5 to 23). AUTHORS' CONCLUSIONS: Flushing of the catheter with a vanco/heparin lock solution leads to a positive overall effect. Depending on the baseline TCVC infection rate it is justified to flush the catheter with a combination of an antibiotic and heparin, if the catheter related infection-rate is high.


Asunto(s)
Profilaxis Antibiótica , Cateterismo Venoso Central/efectos adversos , Infecciones por Bacterias Grampositivas/prevención & control , Neoplasias , Humanos , Neoplasias/terapia , Ensayos Clínicos Controlados Aleatorios como Asunto
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