Simultaneously Targeting Two Coupled Signalling Molecules in the Mesenchymal Stem Cell Support Efficiently Sensitises the Multiple Myeloma Cell Line H929 to Bortezomib.

Several studies have shown that diverse components of the bone marrow (BM) microenvironment play a central role in the progression, pathophysiology, and drug resistance in multiple myeloma (MM). In particular, the dynamic interaction between BM mesenchymal stem cells (BM-MSC) and MM cells has shown great relevance. Here we showed that inhibiting both PKC and NF-κB signalling pathways in BM-MSC reduced cell survival in the MM cell line H929 and increased its susceptibility to the proteasome inhibitor bortezomib. PKC-mediated cell survival inhibition and bortezomib susceptibility induction were better performed by the chimeric peptide HKPS than by the classical enzastaurin inhibitor, probably due to its greatest ability to inhibit cell adhesion and its increased capability to counteract the NF-κB-related signalling molecules increased by the co-cultivation of BM-MSC with H929 cells. Thus, inhibiting two coupled signalling molecules in BM-MSC was more effective in blocking the supportive cues emerging from the mesenchymal stroma. Considering that H929 cells were also directly susceptible to PKC and NF-κB inhibition, we showed that treatment of co-cultures with the HKPS peptide and BAY11-7082, followed by bortezomib, increased H929 cell death. Therefore, targeting simultaneously connected signalling elements of BM-MSC responsible for MM cells support with compounds that also have anti-MM activity can be an improved treatment strategy.

Analgesia perioperatoria mediante bloqueo del plano erector espinal en implante de asistencia ventricular izquierda / Perioperative analgesia by erector spinae plane block in left ventricular assist implant

Los dispositivos de asistencia ventricular izquierda se han convertido en los últimos años en un elemento importante para el manejo del fallo ventricular izquierdo refractario a tratamiento farmacológico. Su implantación (realizada mediante toracotomía izquierda o esternotomía) genera un importante dolor perioperatorio, que puede ser manejado con técnicas de anestesia locorregional. Sin embargo, existe gran controversia sobre su realización en cirugía cardíaca debido a la interferencia con la terapia anticoagulante necesaria en estos pacientes.El bloqueo del plano erector espinal constituye una alternativa a las técnicas locorregionales clásicas, al no producir alteraciones hemodinámicas y no interferir con la terapia antiagregante y anticoagulante, siendo una alternativa a tener en cuenta en cirugía cardíaca. Presentamos un caso de implantación de asistencia ventricular izquierda con realización de dicho bloqueo previo al procedimiento quirúrgico e infusión postoperatoria a través de catéter, obteniéndose resultados satisfactorios en el manejo del dolor perioperatorio.(AU)

In recent years, left ventricular assist devices have become an important element in the management of left ventricular failure refractory to pharmacological treatment. Their implantation (performed by left thoracotomy or sternotomy) generates significant perioperative pain, which can be managed with locoregional anesthesia techniques. However, opinions vary on their use in cardiac surgery due to interference with the anticoagulant therapy required in these patients.The erector spinae plane block is an alternative to classic locoregional techniques. It does not produce hemodynamic alterations and does not interfere with antiplatelet and anticoagulant therapy, and is therefore an alternative to be considered in cardiac surgery. We present a case of left ventricular assist device implantation under this block prior to the surgical procedure and postoperative infusion through a catheter, obtaining satisfactory results in the management of perioperative pain.(AU)

Perioperative analgesia by erector spinae plane block in left ventricular assist implant.

In recent years, left ventricular assist devices have become an important element in the management of left ventricular failure refractory to pharmacological treatment. Their implantation (performed by left thoracotomy or sternotomy) generates significant perioperative pain, which can be managed with locoregional anaesthesia techniques. However, opinions vary on their use in cardiac surgery due to interference with the anticoagulant therapy required in these patients. The erector spinae plane block is an alternative to classic locoregional techniques. It does not produce hemodynamic alterations and does not interfere with antiplatelet and anticoagulant therapy, and is therefore an alternative to be considered in cardiac surgery. We present a case of left ventricular assist device implantation under this block prior to the surgical procedure and postoperative infusion through a catheter, obtaining satisfactory results in the management of perioperative pain.

Características de los adultos con síndrome de Down ingresados en los servicios de medicina interna españoles en el periodo 2005-2014 / Characteristics of adults with Down syndrome hospitalised in Spanish internal medicine departments during 2005-2014

INTRODUCCIÓN Y OBJETIVOS: Los problemas clínicos de los adultos con síndrome de Down parecen diferir de los de la población general. Para entender mejor estas diferencias describimos las características demográficas y clínicas de los adultos con síndrome de Down que ingresaron en los servicios de Medicina Interna españoles en el periodo de 2005-2014. PACIENTES Y MÉTODOS: Estudio observacional retrospectivo sobre datos recogidos en el conjunto mínimo básico de datos de los episodios de ingreso de adultos con síndrome de Down en los servicios de Medicina Interna del Sistema Nacional de Salud desde 2005 hasta 2014. Se analizaron variables epidemiológicas, clínicas y sociales. RESULTADOS: Se registraron 7.548 episodios de ingreso de 3.786 pacientes. El 56,6% eran varones con una edad media (± DE) de 47±13 años. Fallecieron 715 pacientes (18,9%). La mortalidad ajustada a la edad fue 26,6% y su estancia media fue de 9,6±12 días. En 3.684 episodios (48,8%) el ingreso fue por enfermedad respiratoria y en 760 (10%), de origen cardiológico. Las comorbilidades más frecuentes fueron el hipotiroidismo (27,1%; 2.043 episodios), la epilepsia (24,1%; 1.819 episodios) y la demencia (15,4%; 1.162 episodios). CONCLUSIONES: Los ingresos de adultos con síndrome de Down en los servicios de Medicina Interna han aumentado en la última década. Si bien los motivos de ingreso, estancia media y coste por episodio de esta población son similares a los de la población general atendida en Medicina Interna, la mortalidad intrahospitalaria ajustada por edad fue significativamente mayor

INTRODUCTION AND OBJECTIVES: The clinical problems of adults with Down syndrome seem to differ from those of the general population. To better understand these differences, we list the demographic and clinical characteristics of adults with Down syndrome admitted to Spanish internal medicine departments during 2005-2014. PATIENTS AND METHODS: We conducted an observational retrospective study using data collected from the minimum basic data set on hospitalisation episodes of adults with Down syndrome in the internal medicine departments of Spain's National Health System from 2005 to 2014. We analysed the patients' epidemiological, clinical and societal data. RESULTS: A total of 7548 hospitalisation episodes from 3786 patients were recorded. Some 56.6% of the patients were male with a mean age (±SD) of 47±13 years, and 715 of the patients died (18.9%). The age-adjusted mortality was 26.6%, and the mean stay was 9.6±12 days. The hospitalisation was for respiratory disease in 3684 episodes (48.8%) and for cardiac origin in 760 (10%). The most common comorbidities were hypothyroidism (27.1%, 2043 episodes), epilepsy (24.1%, 1819 episodes) and dementia (15.4%, 1162 episodes). CONCLUSIONS: The hospitalisation of adults with Down syndrome in internal medicine departments has increased in the past decade. Although the reasons for hospitalisation, mean stay and cost per episode for this population are similar to those of the general population treated by internal medicine departments, the age-adjusted hospital mortality was significantly greater

Prenatal exposure to oxcarbazepine increases hippocampal apoptosis in rat offspring.

This study assessed apoptosis in the offspring of rats exposed to oxcarbazepine (OXC) from day 7 to 15 of gestation. Three groups of pregnant Wistar rats were used: 1) Control, treated with saline solution; 2) treated with 100 mg/kg OXC; 3) treated with 100 mg/kg of carbamazepine (CBZ, as a positive control for apoptosis); the route of administration was intragastric. Apoptosis was detected at three postnatal ages using the TUNEL technique in the CA1, and CA3 regions of the hippocampus and in the dentate gyrus (DG); neurogenesis was assessed in the DG using an antibody against doublecortin. The litter characteristics were recorded. OXC increased apoptosis in all regions (p < 0.01) at the three ages evaluated. Lamination disruption occurred in CA1 and CA3 due to the neuron absence and to ectopic neurons; there were also malformations in the dorsal lamina of the DG in 38% and 25% of the pups born from rats treated with OXC and CBZ respectively. CBZ also increased apoptosis. No clear effect on neurogenesis in the DG was observed. The size of the litter was smaller (p < 0.01) in the experimental groups. Nineteen-day OXC fetuses had low weight (p < 0.01), but 21 and 30 postnatal days old CBZ and OXC pups were overweight (p < 0.01). The results demonstrate that OXC administered during gestation is pro-apoptotic, alters the cytoarchitecture of the hippocampus, reduces litter size, and probably influences postnatal weight. We provide evidence of the proapoptotic effect of CBZ when administered early in gestation.

Characteristics of adults with Down syndrome hospitalised in Spanish internal medicine departments during 2005-2014. / Características de los adultos con síndrome de Down ingresados en los servicios de medicina interna españoles en el periodo 2005-2014.

INTRODUCTION AND OBJECTIVES: The clinical problems of adults with Down syndrome seem to differ from those of the general population. To better understand these differences, we list the demographic and clinical characteristics of adults with Down syndrome admitted to Spanish internal medicine departments during 2005-2014. PATIENTS AND METHODS: We conducted an observational retrospective study using data collected from the minimum basic data set on hospitalisation episodes of adults with Down syndrome in the internal medicine departments of Spain's National Health System from 2005 to 2014. We analysed the patients' epidemiological, clinical and societal data. RESULTS: A total of 7548 hospitalisation episodes from 3786 patients were recorded. Some 56.6% of the patients were male with a mean age (±SD) of 47±13 years, and 715 of the patients died (18.9%). The age-adjusted mortality was 26.6%, and the mean stay was 9.6±12 days. The hospitalisation was for respiratory disease in 3684 episodes (48.8%) and for cardiac origin in 760 (10%). The most common comorbidities were hypothyroidism (27.1%, 2043 episodes), epilepsy (24.1%, 1819 episodes) and dementia (15.4%, 1162 episodes). CONCLUSIONS: The hospitalisation of adults with Down syndrome in internal medicine departments has increased in the past decade. Although the reasons for hospitalisation, mean stay and cost per episode for this population are similar to those of the general population treated by internal medicine departments, the age-adjusted hospital mortality was significantly greater.

Ovarian stimulation does not influence the uterine immune environment in healthy infertile women.

RESEARCH QUESTION: There is some controversy regarding the impact of ovarian stimulation on immune cells in women undergoing IVF. The study's aim was to determine whether ovarian stimulation affected immune uterine cells in healthy women undergoing IVF. DESIGN: This prospective cohort study included 28 patients undergoing IVF and 47 healthy oocyte donors. Endometrial biopsies were taken in a natural cycle and after ovarian stimulation. All participants had a normal karyotype, pelvic ultrasound and cervical cytology results and thyroid-stimulating hormone concentration, as well as normal glucose and insulin concentrations and inherited and acquired thrombophilia test results. Screening tests including human papillomavirus were normal. Immune cells were analysed using three techniques: fluorescence-activated cell sorting, immunohistochemistry and gene expression. A human leukocyte antigen (HLA)-C tetramer was used as an 'artificial embryo'. The expression of genes including those for tumour necrosis factor (TNF)-α and interleukin-10 (IL-10) was analysed. RESULTS: A comparison was made of the percentage and gene expression of CD56brightCD16- uterine natural killer (uNK), CD56dimCD16+ natural killer cells, CD56-CD16+ natural killer cells and TregCD25+CD4+FoxP3+ cells, uNK binding to the HLA-C tetramer, and TNF-α and IL-10 expression. No between- or within-group differences were observed in natural versus ovarian stimulation cycles. CONCLUSIONS: Ovarian stimulation does not affect the uterine immune cell population or HLA-C binding in healthy women undergoing ovarian stimulation. Further studies are underway to find out if different responses might be seen in women with previous autoimmune disorders.

Neuroblastoma / No disponible

No disponible

Oral anticoagulation in primary care.

Oral anticoagulant therapy is currently widespread in the population and primary care plays an important role in its control in Spain. Younger populations, such as those in prisons, often require this treatment for reasons other than atrial fibrillation, often in relation to valvular or congenital or acquired hypercoagulability situations. The possibility of obtaining the INR by portable coagulometers has allowed primary care physicians to tackle the indication of this therapy and the control of these patients in coordination with haematology services. The emergence of new therapeutic alternatives (Dabigatran, Rivaroxaban, Apixaban and Edoxaban, the so called "ACOD") has permitted the expansion of options for oral anticoagulation in some cases, since they do not require systematic monitoring of their effect and interact with far fewer drugs than their predecessors, although there are still restrictions by the health authorities on their widespread use. This article reviews the different indications of oral anticoagulant therapy according to the new recommendations as well as the clinical scenarios in which it should be used.

Anticoagulación oral en Atención Primaria / Oral anticoagulation in primary care

El tratamiento anticoagulante oral (TAO) está hoy en día ampliamente difundido en la población y en el caso de nuestro país la atención primaria juega un papel relevante en su control. La población joven, como la de los centros penitenciarios, muchas veces requiere de este tratamiento por motivos diferentes a la fibrilación auricular, muchas veces en relación con valvulopatías o situaciones de hipercoagulabilidad congénitas o adquiridas. La posibilidad de obtener mediante coagulómetros portátiles el INR de los pacientes ha permitido que los médicos de atención primaria asuman la indicación de esta terapia y el control de estos pacientes en coordinación con los servicios de hematología. La aparición de nuevas alternativas terapéuticas (Dabigatran, Rivaroxaban, Apixaban y Edoxaban, los llamados 'ACOD') ha permitido ampliar las opciones de anticoagulación oral en algunos casos, aunque todavía existen restricciones por parte de las autoridades sanitarias para su uso generalizado. No requieren monitorización sistemática de su efecto e interaccionan con muchos menos fármacos que sus predecesores. Este artículo repasa las diferentes indicaciones de la terapia anticoagulante oral de acuerdo con las nuevas recomendaciones, así como los escenarios clínicos en los que se debe utilizar (AU)

Oral anticoagulant therapy is currently widespread in the population and primary care plays an important role in its control in Spain. Younger populations, such as those in prisons, often require this treatment for reasons other than atrial fibrillation, often in relation to valvular or congenital or acquired hypercoagulability situations. The possibility of obtaining the INR by portable coagulometers has allowed primary care physicians to tackle the indication of this therapy and the control of these patients in coordination with haematology services. The emergence of new therapeutic alternatives (Dabigatran, Rivaroxaban, Apixaban and Edoxaban, the so called 'ACOD') has permitted the expansion of options for oral anticoagulation in some cases, since they do not require systematic monitoring of their effect and interact with far fewer drugs than their predecessors, although there are still restrictions by the health authorities on their widespread use. This article reviews the different indications of oral anticoagulant therapy according to the new recommendations as well as the clinical scenarios in which it should be used (AU)

Maternal KIR haplotype influences live birth rate after double embryo transfer in IVF cycles in patients with recurrent miscarriages and implantation failure.

STUDY QUESTION: In patients with recurrent miscarriages (RM) or recurrent implantation failure (RIF), does the maternal killer immunoglobulin-like receptor (KIR) haplotype have an impact on live birth rates per cycle after embryo transfer with the patient's own or donated oocytes? SUMMARY ANSWER: After double embryo transfer (DET) in patients with the maternal KIR AA haplotype, a significantly increased early miscarriage rate was observed when the patient's own oocytes were used, and a significantly decreased live birth rate per cycle after embryo transfer was observed when donated oocytes were used. WHAT IS ALREADY KNOWN: Interactions between fetal HLA-C and maternal KIR influence placentation during human pregnancy. There is an increased risk of RM, pre-eclampsia or fetal growth restriction in mothers with the KIR AA haplotype when the fetus has more HLA-C2 genes than the mother. STUDY DESIGN, SIZE AND DURATION: Between 2010 and 2014, we performed a retrospective study that included 291 women, with RM or RIF, who had a total of 1304 assisted reproductive cycles. PARTICIPANTS/MATERIALS, SETTING, METHODS: Pregnancy, miscarriage and live birth rates per cycle after single or DET, categorized by the origin of the oocytes and the presence of maternal KIR haplotypes, were studied. KIR haplotype regions were defined by the presence of the following KIR genes: Cen-A/2DL3; Tel-A/3DL1 and 2DS4; Cen-B/2DL2 and 2DS2; as well as Tel-B/2DS1 and 3DS1. MAIN RESULTS AND THE ROLE OF CHANCE: Higher rates of early miscarriage per cycle after DET with the patient's own oocytes in mothers with the KIR AA haplotype (22.8%) followed by those with the KIR AB haplotype (16.7%) compared with mothers with the KIR BB haplotype (11.1%) were observed (P = 0.03). Significantly decreased live birth rates per cycle were observed after DET of donated oocytes in mothers with the KIR AA haplotype (7.5%) compared with those with the KIR AB (26.4%) and KIR BB (21.5%) haplotypes (P = 0.006). No statistically significant differences were observed for pregnancy, miscarriage and live birth rates per cycle among those with maternal KIR AA, AB and BB haplotypes after single embryo transfer (SET) with the patient's own or donated oocytes. The large number of cases studied strengthens the results and provides sufficient power to the statistical analysis. LIMITATIONS, REASONS FOR CAUTION: During the IVF procedure, DET induces the expression of more than one paternal HLA-C and the oocyte-derived maternal HLA-C in the oocyte-donation cycles probably behaves like paternal HLA-C. Because this was a retrospective study, we did not have data about the HLA-C of the parent, donor, chorionic villi, or infant, which is a limitation because we cannot show differences according to paternal or oocyte donor HLA-C1 and HLA-C2. WIDER IMPLICATIONS OF THE FINDINGS: These new insights could have an impact on the selection of SET in patients with RM or RIF, and a KIR AA haplotype. Also, it may help in oocyte and/or sperm donor selection by HLA-C in patients with RM or RIF and a KIR AA haplotype. STUDY FUNDING/COMPETING INTERESTS: No funding was received for this study. The authors have no conflicts of interest to declare.

Modelling the influence of endothelial heterogeneity on the progression of arterial disease: application to abdominal aortic aneurysm evolution.

We sophisticate a fluid-solid growth computational framework for modelling aneurysm evolution. A realistic structural model of the arterial wall is integrated into a patient-specific geometry of the vasculature. This enables physiologically representative distributions of haemodynamic stimuli, obtained from a rigid-wall computational fluid dynamics analysis, to be linked to growth and remodelling algorithms. Additionally, a quasistatic structural analysis quantifies the cyclic deformation of the arterial wall so that collagen growth and remodelling can be explicitly linked to the cyclic deformation of vascular cells. To simulate aneurysm evolution, degradation of elastin is driven by reductions in wall shear stress (WSS) below homeostatic thresholds. Given that the endothelium exhibits spatial and temporal heterogeneity, we propose a novel approach to define the homeostatic WSS thresholds: We allow them to be spatially and temporally heterogeneous. We illustrate the application of this novel fluid-solid growth framework to model abdominal aortic aneurysm (AAA) evolution and to examine how the influence of the definition of the WSS homeostatic threshold influences AAA progression. We conclude that improved understanding and modelling of the endothelial heterogeneity is important for modelling aneurysm evolution and, more generally, other vascular diseases where haemodynamic stimuli play an important role.

Servicio de nefrología Infantil del Hospital Universitario la Paz / Pediatric Nephrology Department in the Hospital Universitario La Paz

El servicio de Nefrología Infantil, desde sus inicios como Unidad, ha ido adaptándose a los progresos en el campo de la nefrología clínica, la diálisis y el trasplante. Podemos ofertar todas las técnicas de terapia sustitutiva con una amplia experiencia y muy buenos resultados. Asimismo, contamos con equipos multidisciplinarios para atender de forma integral al niño con estas patologías (AU)

Nephrology Pediatric Service has adapted to the progress in the field of clinical nephrology, dialysis and transplantation. We can offer all kind of replacement therapy techniques with extensive experience and good results. We also have multidisplinary teams to address comprehensively the child with these pathologies (AU)

Evolución de la Unidad de Hemano-Oncología y Trasplante Hematopoyético del Hospital Infantil La Paz / Evolution of the Hematology-Oncology and hematopoietic Transplant Unit of the Hospital Infantil la Paz

La Unidad de Hemato-Oncología Pediátrica del Hospital La Paz, fundada en 1965 coincidiendo con la creación del Hospital Infantil, es un centro de referencia a nivel nacional para el diagnóstico y tratamiento de las neoplasias infantiles, así como para la realización de todas las modalidades de Trasplante de Progenitores Hematopoyéticos. Socia fundadora de la Sociedad Internacional de Oncología Pediátrica, así como de las Sociedades Españolas de Hematología y Oncología Pediátricas (SEOP/SEHP, actualmente SEHOP), en las últimas 4 décadas ha formado parte del espectacular avance en calidad de vida y supervivencia del cáncer infantil, alcanzando en la actualidad supervivencias cercanas al 80%. Una parte importante de este éxito ha sido la estrecha colaboración con las demás Unidades y Servicios Médico Quirúrgicos del Hospital Infantil. En la actualidad, la Unidad muestra una actividad creciente tanto del tratamiento oncológico como del trasplante, y sus miembro forman parte activa de las principales sociedades hemato-oncológias pediátricas a nivel nacional e internacional (AU)

The Pediatric Hematology-Oncology Division of La Paz Hospital, founded in 1965 with the whole Children´s Hospital, is a national reference center for diagnosis and treatment of all pediatric malignancies, and for all modalities of Hematopoietic Stem Cell Transplantation. Founding partner of the SIOP (Sociedad Internacional de Oncología Pediátrica) and the Spanish Societies of Hematology and Oncology (formerly SEOP/SEHP), and now SEHOP), it has been part of the spectacular improvement in quality of life and survival of childhood caner in the last four decades reaching today almost 80% survival. An important part of this success is cooperation with other medical and surgical Divisions of the Children´s Hospital. Today, our Division has an increasing activity in both oncologic treatment and transplant and our members are active part of the main national and international pediatric hematologic-oncologic societies (AU)

Punta-onda continua del sueño lento / No disponible

No disponible

Sonographic predictors of surgery in fetal coarctation of the aorta.

OBJECTIVES: Isolated fetal coarctation of the aorta (CoA) has high false-positive diagnostic rates by cardiologists in tertiary centers. Isthmal diameter Z-scores (I), ratio of isthmus to duct diameters (I:D), and visualization of CoA shelf (Shelf) and isthmal flow disturbance (Flow) distinguish hypoplastic from normal aortic arches in retrospective studies, but their ability to predict a need for perinatal surgery is unknown. The aim of this study was to determine whether these four sonographic features could differentiate prenatally cases which would require neonatal surgery in a prospective cohort diagnosed with CoA by a cardiologist. METHODS: From 83 referrals with cardiac disproportion (January 2006 to August 2010), we identified 37 consecutive fetuses diagnosed with CoA. Measurements of I and I:D were made and the presence of Shelf or Flow recorded. Sensitivity, specificity and areas under receiver-operating characteristics curves, using previously reported limits of I < - 2 and I:D < 0.74, as well as Shelf and Flow were compared at first and final scan. Associations between surgery and predictors were compared using multivariable logistic regression and changes in measurements using ANCOVA. RESULTS: Among the 37 fetuses, 30 (81.1%) required surgery and two with an initial diagnosis of CoA were revised to normal following isthmal growth, giving an 86% diagnostic accuracy at term. The median age at first scan was 22.4 (range. 16.6-7.0) weeks and the median number of scans per fetus was three (range, one to five). I < - 2 at final scan was the most powerful predictor (odds ratio, 3.6 (95% CI, 0.47-27.3)). Shelf was identified in 66% and Flow in 50% of fetuses with CoA. CONCLUSION: Incorporation of these four sonographic parameters in the assessment of fetuses with suspected CoA at a tertiary center resulted in better diagnostic precision regarding which cases would require neonatal surgery than has been reported previously.

Loss of poly(ADP-ribose) polymerase-2 leads to rapid development of spontaneous T-cell lymphomas in p53-deficient mice.

Poly(ADP-ribose) polymerase-2 (Parp-2) belongs to a family of enzymes that catalyse poly(ADP-ribosyl)ation of proteins. Parp-2 deficiency in mice (Parp-2(-/-)) results in reduced thymic cellularity associated with increased apoptosis in thymocytes, defining Parp-2 as an important mediator of T-cell survival during thymopoiesis. To determine whether there is a link between Parp-2 and the p53 DNA-damage-dependent apoptotic response, we have generated Parp-2/p53-double-null mutant mice. We found that p53(-/-) backgrounds completely restored the survival and development of Parp-2(-/-) thymocytes. However, Parp-2-deficient thymocytes accumulated high levels of DNA double-strand breaks (DSB), independently of the p53 status, in line with a function of Parp-2 as a caretaker promoting genomic stability during thymocytes development. Although Parp-2(-/-) mice do not have spontaneous tumours, Parp-2 deficiency accelerated spontaneous tumour development in p53-null mice, mainly T-cell lymphomas. These data suggest a synergistic interaction between Parp-2 and p53 in tumour suppression through the role of Parp-2 in DNA-damage response and genome integrity surveillance, and point to the potential importance of examining human tumours for the status of both genes.