Dalbavancin as consolidation therapy for infective endocarditis in patients with comorbidity. A real world experience.

OBJECTIVE: Infective endocarditis (IE) is a potentially life-threatening infection, the incidence of which has in creased in recent decades, particularly among elderly patients with comorbidity. The primary objective of this study was to evaluate the effectiveness of dalbavancin in the consolidation therapy of IE in patients with comorbidity six months after the end of treatment (EOT). METHODS: An observational and retrospective study was conducted on patients with a Charlson Comorbidity Index (CCI) ≥ 3 who were diagnosed with IE and received consolidation therapy with dalbavancin. RESULTS: Forty-eight patients were included, 58.3% were male, mean age of 76.2 years (IQR: 66-88), and a mean age adjusted CCI of 6.5 (IQR: 5-7.5). Definite IE was diagnosed in 77% of cases. The most frequently isolated microorganisms were Staphylococcus aureus (45.8%) followed by Enterococcus spp. (31.3%). Complications of IE were observed in 67.7% of cases, and cardiac surgery was performed in 27% of patients. The primary reason for using dalbavancin was outpatient parenteral antibiotic therapy in 85.4% of cases. The effectiveness at EOT was 93.8%. At six months, six IE-related deaths, four unrelated deaths, and two IE relapses were observed. The effectiveness was 77%. Adverse effects related to DBV were reported in 4.2% of cases, of which 2% were considered serious. CONCLUSIONS: Dalbavancin has proven to be an effective alternative as consolidation antibiotherapy for IE in elderly patients with comorbidity. Moreover, a very favorable safety profile with few associated adverse effects has been observed in this population.

Safety assessment of new nanodiamonds@corrole hybrids addressed by the response of RAW-264.7 macrophages.

Safety assessment of carbon nanomaterials is of paramount importance since they are on the frontline for applications in sensing, bioimaging and drug delivery. The biocompatibility and safety of functionalized nanodiamonds (NDs) are here addressed through the study of the pro-inflammatory response of RAW-264.7 macrophages exposed to new nanodiamonds@corrole hybrids. The corrole unit selected is as a prototype for a hydrophobic organic molecule that can function as a NIR fluorophore reporter, an optical sensor, a photodynamic therapy agent or a photocatalyst. The new functional nanohybrids containing detonated nanodiamonds (NDs) were obtained through esterification using carboxylated NDs and glycol corroles. The success of the covalent functionalization via carbodiimide activation was confirmed through X-ray photoelectron spectroscopy (XPS), Raman and Fourier transform infrared (FTIR) spectroscopy. The UV-vis absorption and emission spectra of the hybrids are additive with respect to the corrole features. The cellular uptake, localization, cell viability and effects on immune cell activation of the new hybrids and of the precursors were carefully investigated using RAW-264.7 macrophages. Overall results showed that the ND@corrole hybrids had no pro-inflammatory effects on the RAW-264.7 macrophage cell line, making them an ideal candidate for a wide range of biomedical applications.

[Statement of the Spanish Interdisciplinary Vascular Prevention Committee on the updated European Guidelines on Cardiovascular Disease Prevention]. / Comentario del CEIPV a las nuevas Guías Europeas de Prevención Cardiovascular 2021.

Statement of the Spanish Interdisciplinary Vascular Prevention Committee on the updated European Guidelines on Cardiovascular Disease Prevention. We present the Spanish adaptation of the 2021 European Guidelines on Cardiovascular Disease (CVD) prevention in clinical practice. The current guidelines besides the individual approach greatly emphasize on the importance of population level approaches to the prevention of cardiovascular diseases. Systematic global CVD risk assessment is recommended in individuals with any major vascular risk factor. Regarding LDL-Cholesterol, blood pressure, and glycemic control in patients with diabetes mellitus, goals and targets remain as recommended in previous guidelines. However, it is proposed a new, stepwise approach (Step 1 and 2) to treatment intensification as a tool to help physicians and patients pursue these targets in a way that fits patient profile. After Step 1, considering proceeding to the intensified goals of Step 2 is mandatory, and this intensification will be based on 10-year CVD risk, lifetime CVD risk and treatment benefit, comorbidities and patient preferences. The updated SCORE algorithm-SCORE2, SCORE-OP- is recommended in these guidelines, which estimates an individual's 10-year risk of fatal and non-fatal CVD events (myocardial infarction, stroke) in healthy men and women aged 40-89 years. Another new and important recommendation is the use of different categories of risk according different age groups (< 50, 50-69 ≥ 70 years). Different flow charts of CVD risk and risk factor treatment in apparently healthy persons, in patients with established atherosclerotic CVD, and in diabetic patients are recommended. Patients with chronic kidney disease are considered high risk or very high-risk patients according to the levels of glomerular filtration rate and albumin-to-creatinine ratio. New lifestyle recommendations adapted to the ones published by the Spanish Ministry of Health as well as recommendations focused on the management of lipids, blood pressure, diabetes and chronic renal failure are included.

Dedicated breast PET value to evaluate BI-RADS 4 breast lesions.

PURPOSE: To evaluate the diagnostic value of dedicated breast PET (dbPET) parallel imaging in mammographically or sonographically detected BI-RADS 4 (Breast Imaging Reporting And Data Systems) lesions. MATERIALS AND METHODS: After institutional review board and patient approvals, 50 consecutive women with 60 BI-RADS 4 breast lesions were prospectively included in the study. All patients underwent Magnetic Resonance Imaging (MRI) and dbPET before biopsy and fusion of both MRI and dbPET images was performed to better locate corresponding lesions. Final findings were compared with histological results. Sensitivity and specificity for dbPET were determined along with their respective 95%-confidence intervals. RESULTS: Histopathology examination revealed 18 malignant lesions (7 in situ and 11 invasive carcinomas) and 42 benign entities. The dedicated breast PET reported no evidence of malignancy in 41 patients, 9 of them with histological diagnosis of neoplasm. Besides, dbPET showed increased metabolically activity in 10 benign lesions and in 9 breast cancers. Two invasive carcinomas were located less than 1 cm from the pectoral muscle, which can explain that they were missed by dbPET because they were outside the field of view (FOV). There were other 6 false negative results, which corresponded to a 0.1 cm invasive lobular carcinoma and 5 in situ carcinomas. Sensitivity and specificity of dbPET were 50% and 76%, respectively. CONCLUSIONS: Our analysis does not allow the recommendation of dbPET for diagnosis of malignancy in BI-RADS 4 mammographic or US abnormalities, mainly due to its high false-negative rate for the detection of in situ carcinomas (85.7%). However, considering the lesions greater than 0.1 cm and included in the FOV, dbPET depicted all invasive carcinomas.

Spanish adaptation of the 2016 European Guidelines on cardiovascular disease prevention in clinical practice. / Adaptación española de las guías europeas de 2016 sobre prevención de la enfermedad cardiovascular en la práctica clínica.

The VI European Guidelines for Cardiovascular Prevention recommend combining population and high-risk strategies with lifestyle changes as a cornerstone of prevention, and propose the SCORE function to quantify cardiovascular risk. The guidelines highlight disease specific interventions, and conditions as women, young people and ethnic minorities. Screening for subclinical atherosclerosis with noninvasive imaging techniques is not recommended. The guidelines distinguish four risk levels (very high, high, moderate and low) with therapeutic objectives for lipid control according to risk. Diabetes mellitus confers a high risk, except for subjects with type 2 diabetes with less than <10 years of evolution, without other risk factors or complications, or type 1 diabetes of short evolution without complications. The decision to start pharmacological treatment of arterial hypertension will depend on the blood pressure level and the cardiovascular risk, taking into account the lesion of target organs. The guidelines don't recommend antiplatelet drugs in primary prevention because of the increased bleeding risk. The low adherence to the medication requires simplified therapeutic regimes and to identify and combat its causes. The guidelines highlight the responsibility of health professionals to take an active role in advocating evidence-based interventions at the population level, and propose effective interventions, at individual and population level, to promote a healthy diet, the practice of physical activity, the cessation of smoking and the protection against alcohol abuse.

[Spanish adaptation of the 2016 European Guidelines on cardiovascular disease prevention in clinical practice]. / Adaptación española de las guías europeas de 2016 sobre prevención de la enfermedad cardiovascular en la práctica clínica.

The VI European Guidelines for Cardiovascular Prevention recommend combining population and high-risk strategies with lifestyle changes as a cornerstone of prevention, and propose the SCORE function to quantify cardiovascular risk. The guidelines highlight disease specific interventions, and conditions as women, young people and ethnic minorities. Screening for subclinical atherosclerosis with noninvasive imaging techniques is not recommended. The guidelines distinguish four risk levels (very high, high, moderate and low) with therapeutic objectives for lipid control according to risk. Diabetes mellitus confers a high risk, except for subjects with type 2 diabetes with less than <10 years of evolution, without other risk factors or complications, or type 1 diabetes of short evolution without complications. The decision to start pharmacological treatment of arterial hypertension will depend on the blood pressure level and the cardiovascular risk, taking into account the lesion of target organs. The guidelines don't recommend antiplatelet drugs in primary prevention because of the increased bleeding risk. The low adherence to the medication requires simplified therapeutic regimes and to identify and combat its causes. The guidelines highlight the responsibility of health professionals to take an active role in advocating evidence-based interventions at the population level, and propose effective interventions, at individual and population level, to promote a healthy diet, the practice of physical activity, the cessation of smoking and the protection against alcohol abuse.

Past climate changes facilitated homoploid speciation in three mountain spiny fescues (Festuca, Poaceae).

Apart from the overwhelming cases of allopolyploidization, the impact of speciation through homoploid hybridization is becoming more relevant than previously thought. Much less is known, however, about the impact of climate changes as a driven factor of speciation. To investigate these issues, we selected Festuca picoeuropeana, an hypothetical natural hybrid between the diploid species F. eskia and F. gautieri that occurs in two different mountain ranges (Cantabrian Mountains and Pyrenees) separated by more than 400 km. To unravel the outcomes of this mode of speciation and the impact of climate during speciation we used a multidisciplinary approach combining genome size and chromosome counts, data from an extensive nuclear genotypic analysis, plastid sequences and ecological niche models (ENM). Our results show that the same homoploid hybrid was originated independently in the two mountain ranges, being currently isolated from both parents and producing viable seeds. Parental species had the opportunity to contact as early as 21000 years ago although niche divergence occurs nowadays as result of a climate-driven shift. A high degree of niche divergence was observed between the hybrid and its parents and no recent introgression or backcrossed hybrids were detected, supporting the current presence of reproductive isolation barriers between these species.

HIN-1: a New Epigenetic Biomarker Crucial for Therapy Selection in Glioblastoma Multiforme.

Glioblastoma multiforme (GBM) is the most common brain tumor in adults. The role of high in normal-1 (HIN-1) as a potential biomarker in combating this disease is being described for the first time in this study. A combination of O6-methylguanine DNA methyltransferase (MGMT) and HIN-1 methylation could be a possible biomarker in therapy choice. Interestingly, survival data shows a similar trend for the methylation of MGMT and for unmethylation of HIN-1 and vice versa. Eighty-eight paraffin-embedded brain tumors were analyzed to screen methylation rates of different genes and evaluate the association between genes methylation and clinicopathologic variables. Our study is the first of its kind to indicate that MGMT and HIN-1 methylation status are inverted (97.7% of methylated ones) and could be new markers in the study of GBM prognosis, especially in the therapy selection.

Drug Cost Avoidance in Prostate Cancer Clinical Trials.

OBJECTIVES: Economic impact of prostate cancer is increasing in relation to its increased incidence and increased patient survival. Clinical trials are essential to evaluate the efficacy and safety of new treatments but may also result in economic benefits by avoiding the cost of the drug. Our objective is to determine the avoided cost in investigational drugs in clinical trials of prostate cancer conducted in a period of 18 years in a tertiary center. MATERIAL AND METHODS: We carried out an observational of prevalence study with retrospective collected data of clinical trials involving currently marketed drugs and cost avoidance during the study period (1996-2013) was calculated. RESULTS: We include in this review five clinical trials on prostate cancer that met selection criteria of 18 performed. All of them were phase III, multicenter, international and with current marketed drugs. 136 patients were included. Total cost avoidance of 696,002€ and an average cost avoidance by clinical trial of 139,200€ were obtained. Average cost avoidance per patient was 5,118€. CONCLUSION: Cost avoidance in investigational drugs is a tangible benefit of clinical trials, whose realization is a source of economic benefits for the hospital, not only by directly generated by each trial. Clinical trials are an exceptional framework for progress in clinical research and real savings for the health system.

Ilarviruses of Prunus spp.: a continued concern for fruit trees.

Prunus spp. are affected by a large number of viruses, causing significant economic losses through either direct or indirect damage, which results in reduced yield and fruit quality. Among these viruses, members of the genus Ilarvirus (isometric labile ringspot viruses) occupy a significant position due to their distribution worldwide. Although symptoms caused by these types of viruses were reported early in the last century, their molecular characterization was not achieved until the 1990s, much later than for other agronomically relevant viruses. This was mainly due to the characteristic liability of virus particles in tissue extracts. In addition, ilarviruses, together with Alfalfa mosaic virus, are unique among plant viruses in that they require a few molecules of the coat protein in the inoculum in order to be infectious, a phenomenon known as genome activation. Another factor that has made the study of this group of viruses difficult is that infectious clones have been obtained only for the type member of the genus, Tobacco streak virus. Four ilarviruses, Prunus necrotic ringspot virus, Prune dwarf virus, Apple mosaic virus, and American plum line pattern virus, are pathogens of the main cultivated fruit trees. As stated in the 9th Report of the International Committee on Taxonomy of Viruses, virions of this genus are "unpromising subjects for the raising of good antisera." With the advent of molecular approaches for their detection and characterization, it has been possible to get a more precise view of their prevalence and genome organization. This review updates our knowledge on the incidence, genome organization and expression, genetic diversity, modes of transmission, and diagnosis, as well as control of this peculiar group of viruses affecting fruit trees.

Only in patients with hormone-dependent breast infiltrating ductal carcinomas, CA15.3 serum levels are inversely correlated with the immunohistochemical expression of Bcl2.

OBJECTIVE: To study possible association between serum CA15.3 levels and immunohistochemical expression of Bcl2 in women affected by infiltrating ductal breast carcinomas. MATERIALS AND METHODS: Two hundred and fifty consecutives women with breast infiltrating ductal carcinomas, aged between 37 and 83 years were included in this study. Serum CA15.3 was determined by electro-chemoluminescence assay (ECLIA-Elecsys 170 Roche). Immunohistochemical staining on tissue sections of 4-5 microns was done by the EnVision method with a heat-induced antigen retrieval step. Antibody used for Bcl2 was (124, Dako, dilution 1/150). Bcl2 expression was assessed as negative (-), weak positive (+) or strong positive (++). RESULTS: In the study group, serum CA15.3 concentrations ranged between 1 and 1743 U/ml, with 25, 50 and 75 percentiles of 12.7, 17.6 and 24.3 U/ml respectively. Serum CA15.3 concentrations were higher in Bcl2 negative cases than in Bcl2 + and Bcl2 ++. We found statistically significant differences between subgroups Bcl2 negative and Bcl2 ++ (p=0.044), between Bcl2 + Bcl2 ++ (p=0.039) and between Bcl2 ++ and Bcl2 -/+ (p=0.013). When we considered 25 U/mL as the threshold of positivity, antigen values>25 U/ml were more frequent in tumors Bcl2- than in Bcl2 ++ (20/52 vs 29/170, p=0.001). The same behavior was observed when comparing the subgroups -/+ with ++ (p=0.001). A very important aspect of our work was that this CA15.3 behavior in relation to the immunohistochemical expression of Bcl2 was maintained in hormone-dependent tumors (ER+), but not in hormone-independent ones. CONCLUSIONS: The results led us to the following consideration: In women affected by infiltrating ductal breast carcinomas, serum levels of CA15.3 associated inversely, both qualitatively and quantitatively, with the immunohistochemical expression of Bcl2, but this fact exists only in hormone-dependent tumors.

Breast carcinomas with hyperprolactinemia at the time of diagnosis-clinico-biological association.

AIM: To analyse association between preoperative hyperprolactinemia serum levels and clinical and biological features of breast tumors. METHODS: Serum levels of prolactin were measured in 253 women with invasive breast cancer. Clinical and biological parameters analysed were age, size, lymph node involvement, distant metastasis and immunohistochemical expression of estrogen receptor, progesterone receptor, androgen receptor, bcl-2, p53 and Ki67. RESULTS: In ductal carcinomas hyperprolactinemia were associated with high age (p = 0.017), and with bcl-2 + + + expression (p = 0.017). Furthermore, serum prolactin values were significantly higher in bcl-2 +++ cases vs negative (p = 0.029); the same happened when we considered the positivity threshold of 25 ng/mL (p = 0.015). CONCLUSION: Is possible to detect in 6% of infiltrating ductal breast carcinomas hyperprolactinemia (>25 ng/mL), being associated only with increasing age, but not with other clinical or biological factors; and 2) the most surprising data was the association between prolactinemia (qualitative (>25 ng/mL) and quantitative) and intense bcl-2 tissue expression, which suggests that, probably, this (prolactinemia) is not a sign of worse prognosis and evolution.

[Encephalitis due to antibodies against the NMDA receptor. A case report of a female patient with no associated tumour and a literature review]. / Encefalitis por anticuerpos contra el receptor NMDA. Descripción de una paciente sin tumor asociado y revisión de la bibliografía.

INTRODUCTION: A severe form of acute encephalitis associated to antibodies against the N-methyl D-aspartate (NMDA) receptor has recently been reported. This clinical picture occurs in young people, not always with an underlying tumour and, despite the initial severity, if identified and treated at an early stage, complete recovery without any kind of sequelae can be achieved. We report on a new case and review the body of knowledge currently available on this recently identified condition. CASE REPORT: A 22-year-old female who visited our centre due to a progressive conduct disorder. Over the days that followed, deterioration in the level of consciousness made it necessary to put her on assisted respiration. Magnetic resonance imaging of the head showed hyperintense lesions mainly in deep temporal regions. A study of the cerebrospinal fluid revealed pleocytosis with a predominance of lymphocytes and antibodies against the NMDA receptor. In the complementary study no underlying tumour was observed. Treatment with corticosteroids and immunoglobulins brought about a slow but steady improvement. After a one-year follow-up there have been no recurrences, no tumours have appeared and the patient has gone back to her usual day-to-day activities. Even a significant temporal atrophy that developed at the beginning of the clinical picture has gradually been seen to resolve itself in neuroimaging studies performed as a control measure. CONCLUSION: Encephalitis due to anti-NMDA antibodies is a disease that has only recently been characterised, but which, according to currently available data, is relatively frequent. Clinically well defined, suspicion of this condition will make it possible to reach a definitive diagnosis and to establish early treatment.

Epigenetic inactivation of the ERK inhibitor Spry2 in B-cell diffuse lymphomas.

Spry2 has been characterized as a negative regulator of the extracellular-regulated kinase (ERK) pathway. In this study we analysed whether epigenetic alterations of hSpry2 promoter occur in human lymphoid/hematopoietic malignancies. Our results revealed that hSpry2 promoter was hypermethylated in the HT cell line derived from a B-cell diffuse lymphoma, which correlated with decreased hSpry2 expression. We detected deregulation of the ERK pathway in these cells, but not in other blood cell lines expressing hSpry2. In addition, the ectopic overexpression of hSpry2 in HT cells drastically reduced the activation of ERK upon phorbol 12-myristate-13-acetate stimulation. Nude mice inoculated with HT mock cells developed tumors seven times larger than those from HT-hSpry2-transfected cells. We found hypermethylation of hSpry2 promoter in 37% (26 cases out of 71) of primary tumors from patients with B-cell diffuse lymphoma but none in normal B lymphocytes from 37 healthy individuals. Finally, we detected that hSpry2 promoter hypermethylation was associated with a significant decrease in the 5-year survival rate. These data suggest that hSpry2 could be important in lymphoid malignancies.

Low genetic variability in the coat and movement proteins of American plum line pattern virus isolates from different geographic origins.

Until very recently isolates of American plum line pattern virus (APLPV) had not been reported from outside North America. The nucleotide sequences corresponding to the movement (MP) and coat (CP) proteins of eight APLPV isolates from five Mediterranean countries were determined. Sequence analysis showed that both MP and CP genes are highly conserved irrespective of geographic origin. The study of the distribution of synonymous and nonsynonymous changes along both open reading frames revealed that these proteins are under the effect of negative purifying selection. The MP and CP of APLPV possess most of the functional motifs described for other members of the genus Ilarvirus.

Electron transfer in Me-blocked heterodimeric alpha,gamma-peptide nanotubular donor-acceptor hybrids.

Bio-inspired cyclopeptidic heterodimers built on beta-sheet-like hydrogen-bonding networks and bearing photoactive and electroactive chromophores on the outer surface have been prepared. Different cross-strand pairwise relationships between the side chains of the cyclic alpha,gamma-peptides afford the heterodimers as three nonequivalent dimeric species. Steady-state and time-resolved spectroscopies clearly show an electron transfer process from pi-extended tetrathiafulvalene, covalently attached to one of the cyclopeptides, to photoexcited [60]fullerene, located on the complementary cyclopeptide. The charge-separated state was stabilized for up to 1 micros before recombining and repopulating the ground state. Our current example shows that cyclopeptidic templates can be successfully used to form light-harvesting/light-converting hybrid ensembles with a distinctive organization of donor and acceptor units able to act as efficient artificial photosystems.

Role of the BRAF mutations in the microsatellite instability genetic pathway in sporadic colorectal cancer.

BACKGROUND AND AIMS: Between 10 and 15% of all cases of colorectal cancer are the result of microsatellite instability (MSI) in the genetic pathway due to an alteration in the DNA repair genes. Tumors with high MSI are characterized by a better prognosis. The BRAF oncogene has been linked to the MSI pathway in tumorogenesis. The objective of this study was to determine whether alterations in BRAF are related to MSI and whether they can result in differences in survival rates. METHODS: The study cohort comprised 351 patients diagnosed with sporadic colorectal cancer. MSI was determined in accordance with the National Cancer Institute's (NCI) recommendations by means of PCR and sequence analyses. Mutational analysis of the BRAF gene was performed by real-time PCR and subsequent sequencing of the altered samples. The methylation pattern of the hMLH1 gene was determined using methylation-specific PCR analyses of bisulfite-treated DNA and the results confirmed by sequencing. RESULTS: Of the patients tested, 6.9% showed high MSI and 3.7% showed a BRAF gene mutation. hMLH1 methylation was observed in 67.2% of the patients with MSI and/or the BRAF alteration. The BRAF mutation was related to the MSI genetic pathway (P < 0.0001) and with hMLH1 methylation. In the analysis of overall survival only MSI had an independent prognostic value for the risk of death. Patients with the BRAF mutation showed a higher risk of death, although this association was found not to be statistically significant. CONCLUSIONS: There is a subgroup of carcinomas which develop via the MSI pathway that carry an alteration of the BRAF gene. This alteration confers a poorer outcome on these patients within the total group of patients with MSI who have a better prognosis. This hypothesis should be further investigated in a larger study population due to the low incidence of BRAF mutations in colorectal cancer.

Mucoepidermoid tumors of the bronchus. Ultrastructural and immunohistochemical study. Histiogenic correlations.

UNLABELLED: Bronchial mucoepidermoid tumors are uncommon neoplasms, morphologically similar to their salivary gland counterpart. The histogenesis is controversial. The aim of this study is to identify myoepithelial cells and speculate on their role in the origin of these tumors. METHODS AND RESULTS: Sixteen bronchial mucoepidermoid tumor surgical specimens were formalin-fixed, paraffin-embedded and studied using a panel of nine antibodies in order to identify a myoepithelial differentiation. Additional antigens against several cytokeratins were performed in four cases and five of the biopies were studied using the electron microscopy. The different types of cells of the primary bronchial mucoepidermoid tumor (mucous luminal, intermediate and squamous) reacted strongly against AE1, CK7, 34bE12 and weakly with AE3, CK18 and CK8/18/19. S-100, alpha-smooth muscle actin, muscle actin HHF35 and alpha-actinin were consistently negative in all cell types. CD10 was positive in very few cells in just one case. CONCLUSION: The immunohistochemical and the ultrastructural study of bronchial mucoepidermiod tumors support a ductal unit origin, without a myoepithelial participation.

Tumorigenic activity of p21Waf1/Cip1 in thymic lymphoma.

The cell cycle inhibitor p21Waf1/Cip1 is among the most important mediators of the tumor suppressor p53. However, there is increasing evidence indicating that p21 could favor tumorigenesis in specific cell types. In particular, the absence of p21 delays the development of thymic lymphomas induced either by ataxia-telangiectasia mutated deficiency or by ionizing irradiation. Here, we extend these observations to the context of p53-deficient mice. The absence of p21 results in a significant extension of the lifespan of p53-null and p53-haploinsufficient mice, and this effect can be attributed exclusively to a decrease in the incidence of spontaneous thymic lymphomas. Specifically, despite the occurrence of a variety of tumor types in the context of p53 deficiency, the only tumors that were significantly impaired by the absence of p21 were thymic lymphomas. Moreover, the absence of p21 also delays the incidence of radiation-induced thymic lymphomas in p53-deficient mice. Interestingly, p21-deficient lymphomas have a higher apoptotic rate than p21-proficient lymphomas, and this could be on the basis of the delayed incidence of thymic lymphomas in the absence of p21. Together, our results indicate that p21 plays an oncogenic role restricted to thymic lymphomas that is mechanistically independent of p53 and associated to a lower tumor apoptotic rate.