Characterization and distribution of Teredinidae assemblage in an estuary in Ceará, Brazil's Northeast.

Teredinids are bivalves mollusks considered the most abundant of invertebrates group of marine wood borers performing an important role in the mangrove environment. This study aimed to characterize the Teredinidae species from the Acaraú River estuary in Ceará and analyse the relationship between the mangrove plant structure and the distribution of Teredinidae, according to gradients estuaries: vertical (flooding) and horizontal (salinity). The collection of mangrove logs with Teredinidae happened in three places within the estuary (inner, median, and upper); in each area, three transects were traced in which three plots were lined off, and a total of 40 logs were collected. Teredinidae species were found and identified: Nausitora fusticula; Neoteredo reynei; Teredo turnerae; Teredo cf. bartschi; Bankia bipennata; Bankia gouldi; Lirodus massa and Lyrodus cf. bipartitus. The Lyrodus cf. bipartitus, Bankia gouldi, and Teredo cf. bartschi species were registered for the first time in Ceará. The distribution and species richness of Teredinidae were directly related to the vertical gradient (flooding) and heterogeneity of the mangrove forest habitat. The data presented here are essential for comprehending the mechanisms responsible for the distribution patterns of the Teredinidae species in the mangrove, contributing to biodiversity conservation in Ceará coastal zones.

Subcellular localization of X-linked inhibitor of apoptosis protein (XIAP) in cancer: Does that matter?

X-linked inhibitor of apoptosis protein (XIAP) finely tunes the balance between survival and death to control homeostasis. XIAP is found aberrantly expressed in cancer, which has been shown to promote resistance to therapy-induced apoptosis and confer poor outcome. Despite its predominant cytoplasmic localization in human tissues, growing evidence implicates the expression of XIAP in other subcellular compartments in sustaining cancer hallmarks. Herein, we review our current knowledge on the prognostic role of XIAP localization and discuss molecular mechanisms underlying differential biological functions played in each compartment. The comprehension of XIAP subcellular shuttling and functional dynamics might provide the rationale for future anticancer therapeutics.

Silver Nanoparticles-Composing Alginate/Gelatine Hydrogel Improves Wound Healing In Vivo.

Polymer hydrogels have been suggested as dressing materials for the treatment of cutaneous wounds and tissue revitalization. In this work, we report the development of a hydrogel composed of natural polymers (sodium alginate and gelatin) and silver nanoparticles (AgNPs) with recognized antimicrobial activity for healing cutaneous lesions. For the development of the hydrogel, different ratios of sodium alginate and gelatin have been tested, while different concentrations of AgNO3 precursor (1.0, 2.0, and 4.0 mM) were assayed for the production of AgNPs. The obtained AgNPs exhibited a characteristic peak between 430-450 nm in the ultraviolet-visible (UV-Vis) spectrum suggesting a spheroidal form, which was confirmed by Transmission Electron Microscopy (TEM). Fourier Transform Infra-red (FT-IR) analysis suggested the formation of strong intermolecular interactions as hydrogen bonds and electrostatic attractions between polymers, showing bands at 2920, 2852, 1500, and 1640 cm-1. Significant bactericidal activity was observed for the hydrogel, with a Minimum Inhibitory Concentration (MIC) of 0.50 µg/mL against Pseudomonas aeruginosa and 53.0 µg/mL against Staphylococcus aureus. AgNPs were shown to be non-cytotoxic against fibroblast cells. The in vivo studies in female Wister rats confirmed the capacity of the AgNP-loaded hydrogels to reduce the wound size compared to uncoated injuries promoting histological changes in the healing tissue over the time course of wound healing, as in earlier development and maturation of granulation tissue. The developed hydrogel with AgNPs has healing potential for clinical applications.

Metabolizable energy levels for meat-type quails at starter phase

This experiment was conducted to evaluate the effects of dietary nitrogen-corrected apparent metabolizable energy (AMEn) levels on meat-type quail performance and carcass traits from 1 to 14d of age. A total of 1120 not sexed meat-type quails were randomly distributed to seven treatments, with eight replicates with 20 quails each. A basal corn and soybean meal-based diet was formulated to meet or exceed quail nutritional requirements, except for ME. Graded levels of soybean oil were added to the basal diet in replacement, to sand, to obtain dietary treatments (2,600; 2,700; 2,800; 2,900; 3,000; 3,100 and 3,200 KcalAMEn/kg diet). Data were analyzed as one-way ANOVA and optimum AMEn levels were estimated using polynomial regression model. Increasing in dietary AMEn levels elicited a linear decrease (p0.05) by AMEn. Based on the results, the dietary AMEn level that warrants adequate performance and carcass traits of meat-type quails from 1 to 14d of age is 2,820 Kcal/kg diet.

Metabolizable energy levels for meat-type quails at starter phase

This experiment was conducted to evaluate the effects of dietary nitrogen-corrected apparent metabolizable energy (AMEn) levels on meat-type quail performance and carcass traits from 1 to 14d of age. A total of 1120 not sexed meat-type quails were randomly distributed to seven treatments, with eight replicates with 20 quails each. A basal corn and soybean meal-based diet was formulated to meet or exceed quail nutritional requirements, except for ME. Graded levels of soybean oil were added to the basal diet in replacement, to sand, to obtain dietary treatments (2,600; 2,700; 2,800; 2,900; 3,000; 3,100 and 3,200 KcalAMEn/kg diet). Data were analyzed as one-way ANOVA and optimum AMEn levels were estimated using polynomial regression model. Increasing in dietary AMEn levels elicited a linear decrease (p<0.01) in feed intake and nutrient intake (AMEn, protein and lysine). Quail weight gain and final body weight exhibited a quadratic response (p<0.03) to increased AMEn levels, being both optimized at 2820 KcalAMEn/kg diet. Graded AMEn levels elicited a linear increase (p<0.01) in carcass dry matter and fat content, whereas moisture content was linearly decreased (p<0.01). The protein content of the carcasses was not influenced (p>0.05) by AMEn. Based on the results, the dietary AMEn level that warrants adequate performance and carcass traits of meat-type quails from 1 to 14d of age is 2,820 Kcal/kg diet.(AU)

Time-course effects of aerobic exercise training on cardiovascular and renal parameters in 2K1C renovascular hypertensive rats

Exercise training (Ex) has been recommended for its beneficial effects in hypertensive states. The present study evaluated the time-course effects of Ex without workload on mean arterial pressure (MAP), reflex bradycardia, cardiac and renal histology, and oxidative stress in two-kidney, one-clip (2K1C) hypertensive rats. Male Fischer rats (10 weeks old; 150–180 g) underwent surgery (2K1C or SHAM) and were subsequently divided into a sedentary (SED) group and Ex group (swimming 1 h/day, 5 days/week for 2, 4, 6, 8, or 10 weeks). Until week 4, Ex decreased MAP, increased reflex bradycardia, prevented concentric hypertrophy, reduced collagen deposition in the myocardium and kidneys, decreased the level of thiobarbituric acid-reactive substances (TBARS) in the left ventricle, and increased the catalase (CAT) activity in the left ventricle and both kidneys. From week 6 to week 10, however, MAP and reflex bradycardia in 2K1C Ex rats became similar to those in 2K1C SED rats. Ex effectively reduced heart rate and prevented collagen deposition in the heart and both kidneys up to week 10, and restored the level of TBARS in the left ventricle and clipped kidney and the CAT activity in both kidneys until week 8. Ex without workload for 10 weeks in 2K1C rats provided distinct beneficial effects. The early effects of Ex on cardiovascular function included reversing MAP and reflex bradycardia. The later effects of Ex included preventing structural alterations in the heart and kidney by decreasing oxidative stress and reducing injuries in these organs during hypertension.

Time-course effects of aerobic exercise training on cardiovascular and renal parameters in 2K1C renovascular hypertensive rats.

Exercise training (Ex) has been recommended for its beneficial effects in hypertensive states. The present study evaluated the time-course effects of Ex without workload on mean arterial pressure (MAP), reflex bradycardia, cardiac and renal histology, and oxidative stress in two-kidney, one-clip (2K1C) hypertensive rats. Male Fischer rats (10 weeks old; 150-180 g) underwent surgery (2K1C or SHAM) and were subsequently divided into a sedentary (SED) group and Ex group (swimming 1 h/day, 5 days/week for 2, 4, 6, 8, or 10 weeks). Until week 4, Ex decreased MAP, increased reflex bradycardia, prevented concentric hypertrophy, reduced collagen deposition in the myocardium and kidneys, decreased the level of thiobarbituric acid-reactive substances (TBARS) in the left ventricle, and increased the catalase (CAT) activity in the left ventricle and both kidneys. From week 6 to week 10, however, MAP and reflex bradycardia in 2K1C Ex rats became similar to those in 2K1C SED rats. Ex effectively reduced heart rate and prevented collagen deposition in the heart and both kidneys up to week 10, and restored the level of TBARS in the left ventricle and clipped kidney and the CAT activity in both kidneys until week 8. Ex without workload for 10 weeks in 2K1C rats provided distinct beneficial effects. The early effects of Ex on cardiovascular function included reversing MAP and reflex bradycardia. The later effects of Ex included preventing structural alterations in the heart and kidney by decreasing oxidative stress and reducing injuries in these organs during hypertension.

Occurrence of Neospora caninum and Toxoplasma gondii DNA in brain tissue from hoary foxes (Pseudalopex vetulus) in Brazil.

The hoary fox (Pseudalopex vetulus) is a wild canid native to Brazil and is commonly found in the semiarid northeastern area living in contact with cattle. The main purpose of this study was to investigate the presence of Neospora caninum and Toxoplasma gondii DNA in hoary foxes, in the state of Paraíba, Brazil. Brain tissue samples were collected from 49 hoary foxes. From the samples, DNA extraction and the polymerase chain reaction (PCR) were performed using specific primers for N. caninum and T. gondii. The prevalences found were 14.3% (7/49) for T. gondii and 12.2% (6/49) for N. caninum. The molecular identities of the amplified products were confirmed by means of the sequencing reaction. This study demonstrated the presence of N. caninum and T. gondii DNA in free-ranging hoary foxes in Brazil for the first time, thus confirming that this species is an intermediate host.

Rosai-Dorfman disease: a report of eight cases in a tertiary care center and a review of the literature

Rosai-Dorfman disease (RDD) is a nonmalignant histiocytic disorder of unknown origin that is extremely rare. By immunohistochemistry, the RDD cells are characteristically S-100 positive and CD1a negative. Emperipolesis is a common histopathological finding, although not specific for RDD. Lymph node and cutaneous manifestations are most frequent, but diverse organs can be affected. The clinical course is unpredictable regardless of treatment. Here, we present a series of 8 cases presenting lymph node and/or cutaneous lesions. Lymph node involvement was seen in diverse regions, including mediastinal and retroperitoneal. The treatment response to steroids was diversified, and the chemotherapy response was disappointing. Associated autoimmune diseases (Sjögren syndrome and antiphospholipid syndrome) were observed in 2 patients. Regardless of therapy modality, these patients exhibited a favorable prognosis in a follow-up duration that ranged from 15 to 80 months.

Rosai-Dorfman disease: a report of eight cases in a tertiary care center and a review of the literature.

Rosai-Dorfman disease (RDD) is a nonmalignant histiocytic disorder of unknown origin that is extremely rare. By immunohistochemistry, the RDD cells are characteristically S-100 positive and CD1a negative. Emperipolesis is a common histopathological finding, although not specific for RDD. Lymph node and cutaneous manifestations are most frequent, but diverse organs can be affected. The clinical course is unpredictable regardless of treatment. Here, we present a series of 8 cases presenting lymph node and/or cutaneous lesions. Lymph node involvement was seen in diverse regions, including mediastinal and retroperitoneal. The treatment response to steroids was diversified, and the chemotherapy response was disappointing. Associated autoimmune diseases (Sjögren syndrome and antiphospholipid syndrome) were observed in 2 patients. Regardless of therapy modality, these patients exhibited a favorable prognosis in a follow-up duration that ranged from 15 to 80 months.

Digestibilidade do cálcio de ingredientes para suínos, avaliada por meio de dois métodos / Calcium digestibility from feedstuffs for pigs evaluated using two methods

Determinaram-se os coeficientes de digestibilidade aparente e verdadeira do cálcio (Ca) de ingredientes para suínos por meio de dois métodos. Foram utilizados 60 suínos machos castrados, alojados em gaiolas de metabolismo e distribuídos em delineamento experimental inteiramente ao acaso, em arranjo fatorial 2 x 10 (métodos x tratamentos) e seis repetições por tratamento. Os tratamentos consistiram em oito alimentos, uma ração basal (0,072% de Ca total) e uma ração com baixo teor de Ca (0,018%). Os coeficientes de digestibilidade aparente e verdadeira do Ca foram avaliados utilizando-se simultaneamente dois métodos: coleta total de fezes e coleta de fezes com indicador fecal (cinza ácida insolúvel - CAI). Os coeficientes de digestibilidade verdadeira do Ca, obtidos pelo método de coleta total e pelo método de indicador fecal, foram, respectivamente: calcário calcítico 1, 84,80 e 87,33%; calcário calcítico 2, 84,19 e 86,32%; fosfato bicálcico, 79,36 e 84,55%; fosfato monobicálcico, 83,83 e 85,81%; calcário dolomítico, 85,65 e 87,39%; farinha de carne e ossos (40% PB), 70,00 e 68,64%; farinha de carne e ossos (50% PB), 66,92 e 68,03%; farinha de vísceras, 73,40 e 73,95%, lactato de Ca, 95,10 e 97,33%. Não houve diferença significativa (P>0,05) entre os métodos avaliados coleta total (80,14%) e indicador fecal (82,15%).(AU)

The coefficients of apparent and true digestibility of calcium (Ca) of eight feedstuffs for pigs were determined. A total of 60 barrows were housed in metabolism cages and distributed in a completely randomized design in a factorial 2 X 10 (treatments X methods) and 6 replicates per treatment. Treatments consisted of eight feedstuffs, a basal diet (0.072% Ca) and a diet with low Ca content (0.018%). The coefficients of apparent and true digestibility of Ca were determined using two methods simultaneously: total fecal collection and fecal marker (Acid Insoluble Ash - AIA). The true digestibility coefficients of Ca, obtained by the total fecal collection and the fecal marker methods were respectively: Limestone 1, 84.80 and 87.33%; Limestone 2, 84.19% and 86.32; Dicalcium Phosphate, 79.36 and 84.55%; Monodicalcium Phosphate, 83.83 and 85.81%, Dolomitic Limestone, 87.39% and 85.65; Meat and Bone Meal (40% CP), 70.00 and 68,64%; Meat and Bone Meal (50% CP), 66.92% and 68.03; Poultry by Product Meal, 73.40 and 73.95%, Calcium Lactate, 95.10 and 97.33%. There was no significant difference (P>0.05) between the total fecal collection (80.14%) and fecal marker (82.15%) with the methods evaluated.(AU)

Digestibilidade do cálcio de ingredientes para suínos, avaliada por meio de dois métodos / Calcium digestibility from feedstuffs for pigs evaluated using two methods

Determinaram-se os coeficientes de digestibilidade aparente e verdadeira do cálcio (Ca) de ingredientes para suínos por meio de dois métodos. Foram utilizados 60 suínos machos castrados, alojados em gaiolas de metabolismo e distribuídos em delineamento experimental inteiramente ao acaso, em arranjo fatorial 2 x 10 (métodos x tratamentos) e seis repetições por tratamento. Os tratamentos consistiram em oito alimentos, uma ração basal (0,072% de Ca total) e uma ração com baixo teor de Ca (0,018%). Os coeficientes de digestibilidade aparente e verdadeira do Ca foram avaliados utilizando-se simultaneamente dois métodos: coleta total de fezes e coleta de fezes com indicador fecal (cinza ácida insolúvel - CAI). Os coeficientes de digestibilidade verdadeira do Ca, obtidos pelo método de coleta total e pelo método de indicador fecal, foram, respectivamente: calcário calcítico 1, 84,80 e 87,33%; calcário calcítico 2, 84,19 e 86,32%; fosfato bicálcico, 79,36 e 84,55%; fosfato monobicálcico, 83,83 e 85,81%; calcário dolomítico, 85,65 e 87,39%; farinha de carne e ossos (40% PB), 70,00 e 68,64%; farinha de carne e ossos (50% PB), 66,92 e 68,03%; farinha de vísceras, 73,40 e 73,95%, lactato de Ca, 95,10 e 97,33%. Não houve diferença significativa (P>0,05) entre os métodos avaliados coleta total (80,14%) e indicador fecal (82,15%)...

The coefficients of apparent and true digestibility of calcium (Ca) of eight feedstuffs for pigs were determined. A total of 60 barrows were housed in metabolism cages and distributed in a completely randomized design in a factorial 2 X 10 (treatments X methods) and 6 replicates per treatment. Treatments consisted of eight feedstuffs, a basal diet (0.072% Ca) and a diet with low Ca content (0.018%). The coefficients of apparent and true digestibility of Ca were determined using two methods simultaneously: total fecal collection and fecal marker (Acid Insoluble Ash - AIA). The true digestibility coefficients of Ca, obtained by the total fecal collection and the fecal marker methods were respectively: Limestone 1, 84.80 and 87.33%; Limestone 2, 84.19% and 86.32; Dicalcium Phosphate, 79.36 and 84.55%; Monodicalcium Phosphate, 83.83 and 85.81%, Dolomitic Limestone, 87.39% and 85.65; Meat and Bone Meal (40% CP), 70.00 and 68,64%; Meat and Bone Meal (50% CP), 66.92% and 68.03; Poultry by Product Meal, 73.40 and 73.95%, Calcium Lactate, 95.10 and 97.33%. There was no significant difference (P>0.05) between the total fecal collection (80.14%) and fecal marker (82.15%) with the methods evaluated...

Reproductive cycle and embryonic development of the gastropod Melampus coffeus (Linnaeus, 1758) (Ellobiidae) in the Brazilian Northeast.

Melampus coffeus belongs to a primitive group of pulmonate mollusks found mainly in the upper levels of the marine intertidal zone. They are common in the neotropical mangroves. Little is known about the biology of this species, particularly about its reproduction. The aim of this study was to 1) characterize the morphology and histology of M. coffeus' gonad; 2) describe the main gametogenesis events and link them to a range of maturity stages; 3) chronologically evaluate the frequency of the different maturity stages and their relation to environmental factors such as water, air and sediment temperatures, relative humidity, salinity and rainfall; and 4) characterize M. coffeus' spawning, eggs and newly hatched veliger larvae. Samples were collected monthly between February, 2007 and January, 2009 from the mangroves of Praia de Arpoeiras, Acaraú County, State of Ceará, northeastern Brazil. The characterization of the gonad development stages was carried out using routine histological techniques. The results of this study show that Melampus coffeus is a simultaneous hermaphrodite. The follicles have masculine and feminine elements, interleaved within the gonad. M. coffeus presents a well-defined synchronous reproductive cycle, showing successive maturation, release and resting periods. The average diameter of the oocytes was negatively correlated with salinity and positively correlated with rainfall. The results show that no reproductive activity occurs during periods of drought. After the dry season, the increasing rainfall levels and reduced salinity lead to the appearance of very dense populations, predominantly composed of small individuals.

LASSBio-881: an N-acylhydrazone transient receptor potential vanilloid subfamily type 1 antagonist orally effective against the hypernociception induced by capsaicin or partial sciatic ligation.

BACKGROUND AND PURPOSE: Compound LASSBio-881 is an orally effective antinociceptive that binds to cannabinoid receptors and is active mainly on the neurogenic component of pain models. We investigated whether transient receptor potential vanilloid subfamily type 1 (TRPV1) channels are involved in the effects of LASSBio-881. EXPERIMENTAL APPROACH: Modulation of capsaicin (CAP)- and low pH-induced currents was evaluated in TRPV1-expressing Xenopus oocytes. In vivo effects were evaluated in CAP-induced acute and inflammatory changes in nociception, as well as in partial sciatic ligation-induced thermal hypernociception. KEY RESULTS: LASSBio-881 inhibited TRPV1 currents elicited by CAP with an IC(50) of 14 microM, and inhibited proton-gated currents by 70% at 20 microM. Functional interaction with CAP was surmountable. Locally applied LASSBio-881 decreased time spent in CAP-elicited nocifensive behaviour by 30%, and given orally it reduced measures of CAP- or carrageenan-evoked thermal hypernociception by 60 and 40% respectively. In addition, LASSBio-881 decreased the paw withdrawal responses to thermal stimuli of animals with sciatic neuropathy 7-11 days after nerve ligation, at a dose of 300 micromol*kg(-1)*day(-1) p.o. At this dose, hyperthermia was not observed within 4 h following oral administration. CONCLUSIONS AND IMPLICATIONS: LASSBio-881 is a TRPV1 antagonist that apparently competes with CAP. Accordingly, LASSBio- 881 inhibited nociception in models of acute, inflammatory and neuropathic pain presumed to involve TRPV1 signalling. These in vivo actions were not hindered by hyperthermia, a common side effect of other TRPV1 antagonists. We propose that the antinociceptive properties of LASSBio-881 are due to TRPV1 antagonism, although other molecular interactions may contribute to the effects of this multi-target drug candidate.

Genomic variation at the MDR1 promoter and P-glycoprotein expression and activity in AML patients.

Sequence variation at the proximal MDR1 promoter of 72 patients with acute myeloid leukemia (AML) was investigated and its association with P-glycoprotein (Pgp) expression and activity using flow cytometry were analyzed. Two variants were found: -129T/C and a non-described A/T substitution at position +68 of intron 1 in one patient. Three different genotypes were identified for single nucleotide polymorphism (SNP) -129T/C: 60 patients TT, 11 individuals TC, and 1 CC. No significant association was found between SNP variants and Pgp activity and expression, at protein level. Our data also suggested that an evaluation of MDR1 promoter polymorphisms is of uncertain prognostic value.

Pomolic acid-induced apoptosis in cells from patients with chronic myeloid leukemia exhibiting different drug resistance profile.

Pomolic acid (PA) is a pentacyclic triterpene which has been previously described as active in inhibiting the growth of K562 cell line-originated from chronic myeloid leukemia (CML) in blast crisis-and its vincristine-resistant derivative K562-Lucena1. In this work, cells from CML patients were treated with PA and the apoptotic index was compared with the multidrug resistance (MDR) profile and clinical status of the patients. Our findings show that PA 12.5 microg/ml at 24 h (p = 0.000), at 48 h (p = 0.012) and at 72 h (p = 0.005) has a potent apoptotic index in CML cells as compared to mononuclear cells from healthy donors. PA was capable to induce apoptosis in cells from CML patients exhibiting functional MDR phenotype but not in P-glycoprotein expression. In addition, PA was effective in chronic as well as in blast phase of CML. Moreover, similar apoptotic index induced by PA was observed in low, intermediate and high-risk Sokal score as well as in samples from the group of patients with clinical resistance to interferon and/or imatinib and non-treated patients. These results suggest that PA may be an effective agent for the treatment of CML.

Retinoblastoma-related geneRb2/p130 are rarely mutated in Burkitt's lymphoma from Brazil.

It has been suggested that alterations of cell cycle genes probably contribute to the pathogenesis of endemic Burkitt's lymphoma (BL) in addition to c-MYC translocation. Mutations disrupting the normal nuclear localization signal of the retinoblastoma-related gene Rb2/p130 have been documented in BL cell lines and primary tumors from endemic areas. The aim of this study was to investigate the involvement of Rb2/p130 gene in the pathogenesis of sporadic BL in Brazil. DNA samples from 26 pediatric BL tumors and two healthy blood donors were screened by PCR amplification followed by single strand conformation polymorphism analysis of exons 19 and 20 (B domain) and exons 21 and 22 (C-terminus), where most of the point mutations in the Rb2/p130 gene were identified. No abnormal band shifts were present in the samples analyzed. We concluded that mutations in exons 19-22 of the Rb2/p130 are unlikely to be involved directly in the pathogenesis of sporadic Brazilian BL.

Apoptotic effect of fludarabine is independent of expression of IAPs in B-cell chronic lymphocytic leukemia.

Despite the efficiency of fludarabine in the induction of clinical responses in B-cell chronic lymphocytic leukemia (B-CLL) patients, resistance to this drug has been documented. The present study tested whether resistance to fludarabine is related to the expression of inhibitor of apoptosis proteins (IAPs) family members. We analyzed the expression of c-IAP1, c-IAP2 and XIAP, by immunocytochemistry, in 30 blood samples from B-CLL patients and correlated protein expression to fludarabine-induced apoptosis estimated by an annexin-V assay. Expression of c-IAP1, c-IAP2 and XIAP were found predominantly in the cytoplasm, and a wide range of staining intensities was observed among distinct samples. No correlation was found between the levels of IAPs expression and prognostic factors such as age, gender, lymphocyte doubling time, white blood cell count or previous treatment. The expression of IAPs also failed to predict the sensitivity to fludarabine-induced apoptosis. Alternative pathways of cell death may explain the independence of fludarabine-induced apoptosis from the high expression of IAPs.

p53 protein expression does not correlate with EBV status in childhood B non-Hodgkin lymphomas.

BACKGROUND: The p53 tumor suppressor gene is affected in a wide range of human cancers, including hematological malignancies. This gene encodes a nuclear phosphoprotein p53, which plays a key role in cell cycle arrest, induction of apoptosis, and DNA repair. Mutations of the p53 gene often lead to the accumulation of the mutated protein in the nucleus of neoplastic cells. However, p53 protein expression is frequently detected in non-Hodgkin lymphomas (NHL) without any correlation with p53 mutations. This discordance suggests the existence of other mechanisms to stabilize the p53 protein, including binding of p53 protein to viral proteins. p53 protein has been shown to bind to proteins encoded by the Epstein-Barr virus (EBV). PROCEDURE: The aim of this study was to analyze p53 expression in childhood B-NHL and correlate its expression in the absence of p53 mutations with EBV in order to investigate a possible involvement of EBV in p53 stabilization. DESIGNS AND METHODS: Tumor specimens from 35 children with B-NHL were analyzed by immunohistochemistry (IHC) with the DO7 monoclonal antibody, which recognizes an epitope at N-terminus of p53 protein and reacts with wild type and mutant proteins. To detect p53 mutations, PCR/SSCP and sequencing were performed. EBV status was determinated using a specific PCR technique. RESULTS: The overall frequency of p53 immunostaining positivity was 45% (16 of 35). p53 mutations were detected in nine patients (25.6%). p53 immunoreactivity was observed in all cases with mutations. Additionally, we identified 7 p53 positive cases among 26 tumors without mutations. EBV DNA was detected in 24 of 35 cases. Four patients with p53 expression dissociated from mutation were EBV positive. No statistically significant association was found between p53 expression and EBV cases despite the exclusion of those patients in which p53 expression was related with p53 mutations (P = 0.28 and 0.54, respectively). CONCLUSIONS: Our results suggested that in childhood B-NHL, the expression of p53 dissociated from mutations could not be related to EBV infection. Further studies with larger patient sets will be necessary to determinate if EBV-encoded protein may play a role for nuclear accumulation of p53 protein.