Search

Out of 956, there were 95 (10%) CD56+ APL patients treated with PETHEMA ATRA and chemotherapy. CD56+ expression was associated with high WBC, BCR3 isoform, and co-expression of CD2, CD34, CD7, HLA-DR, CD15, and CD117 antigens. CD56+ vs CD56- APL presented higher induction death rate (16% vs 8%, p = .02) and 5-years cumulative incidence of relapse (33% versus 10%, p = .006), irrespectively of the Sanz score (low-risk 47% versus 5%, p < .001; intermediate 23% versus 7%, p < .001; and high-risk 42% versus 21%, p = .007). In the multivariate analysis, CD56 + (p < .0001), higher relapse-risk score (p = .001), and male gender (p = .05) retained the independent predictive value. CD56+ APL also showed a greater risk of CNS relapse (6% versus 1%, p < .001) and lower 5-year OS (75% versus 83%, p = .003). The AIDA-based LPA2012 trial, with an intensified consolidation schedule for CD56+ APL, will elucidate whether an intensified consolidation schedule could mitigate the relapse rate in this setting.

Although additional cytogenetic abnormalities (ACA) do not affect the prognosis of patients with t(15;17) acute promyelocytic leukemia (APL), the role of a complex karyotype (CK) is yet to be clarified. We aimed to investigate the relationship of CK with relapse incidence in 1559 consecutive APL patients enrolled in three consecutive trials. Treatment consisted of AIDA induction followed by risk-adapted consolidation. A CK (CK) was defined as the presence of >= 2 ACA, and a very CK (CK+) as >= 3 ACA. Eighty-nine patients (8%) had a CK, of whom 41 (4%) had CK+. The 5-year cumulative incidence of relapse (CIR) in patients with CK was 18%, and 12% in those with

A risk-adapted strategy based on all-trans retinoic acid (ATRA) and anthracycline monochemotherapy (PETHEMALPA99 trial) has demonstrated a high antileukemic efficacy in acute promyelocytic leukemia. We designed a new trial (LPA2005) with the objective of achieving stepwise improvements in outcome. Between July 2005 and April 2009, low- and intermediate-risk patients (leukocytes < 10 x 10(9)/L) received a reduced dose of mitoxantrone for the second consolidation course, whereas high-risk patients younger than 60 years of age received cytarabine combined with ATRA and idarubicin in the first and third consolidation courses. Of 372 patients attaining complete remission after ATRA plus idarubicin (92.5%), 368 proceeded to consolidation therapy. For low- and intermediate-risk patients, duration of neutropenia and thrombocytopenia and hospital stay were significantly reduced without sacrificing antileukemic efficacy, compared with the previous LPA99 trial. For high-risk patients, the 3-year relapse rate was significantly lower in the LPA2005 trial (11%) than in the LPA99 (26%; P = .03). Overall disease-free survival was also better in the LPA2005 trial (P = .04). In conclusion, the lower dose of mitoxantrone resulted in a significant reduction of toxicity and hospital stay while maintaining the antileukemic activity, and the combination of ATRA, idarubicin, and cytarabine for high-risk acute promyelocytic leukemia significantly reduced the relapse rate in this setting. Registered at http://www.clinicaltrials.gov as NCT00408278. (Blood. 2010; 115(25):5137-5146)

The management of pregnant women with acute promyelocytic leukemia (APL) is a challenge with limited evidence-based information available. We are reporting a series of 14 consecutive pregnant women with APL who were registered in the PETHEMA Data Centre between 1996 and 2012. APL was diagnosed during early pregnancy in five women, late pregnancy in seven, and two additional patients after delivery in an extremely poor clinical condition (pulmonary and cerebral hemorrhage). Eleven of the 12 patients eligible for induction therapy with all-trans retinoic acid and idarubicin achieved complete remission (CR 92 %) and are still in the first CR. All early pregnancies ended in abortion (four induced and one spontaneous), with four of them achieving CR. Eight of nine women in late pregnancy delivered a healthy infant (six cesarean section and two vaginal delivery). All eight babies developed normally. Our results confirm a high cure rate for pregnant women with APL who received all-trans retinoic acid and idarubicin for induction therapy, and an excellent outcome for babies when the disease is diagnosed during late pregnancy.

Marine invertebrates exhibit both chemokinesis and chemotaxis phenomena, induced in most cases by the release of water-borne peptides or pheromones. In mollusks, several peptides released during egg laying improve both male attraction and mating. Unlike other cephalopods, Octopus vulgaris adopts an indirect internal fertilization (Hanlon and Messenger, 2006). The existence of mechanisms and factors that might mobilize and attract spermatozoa toward the eggs remains not clear in this species. The only data that support the occurrence of a chemical communication process in octopus fertilization are based on the demonstration of an acrosome-like reaction induced by progesterone (Tosti et al., 2001). Here we report for the first time the identification and characterization of a chemoattractant peptide (Octo-Pep) isolated from mature eggs of Octopus vulgaris females. By using two-chamber and time-lapse microscopy assays, we demonstrate that this bioactive peptide is able to i ncrease sperm motility and to induce chemotaxis by changing the octopus spermatozoa swimming behavior in a dose-dependent manner. We also provide evidence that chemotaxis in O. vulgaris requires the presence of extracellular calcium and membrane protein phophorylation at tyrosine. In this frame, we propose Octopus as a model to investigate chemotactic mechanisms in sexual communication to unveil the detailed steps of the fertilization strategy in marine animals with internal fertilization.

The marine environment comprises complex ecosystems and many of organisms are known to possess bioactive components as a common means of self-defence or for the protections of eggs and embryos. Lately, many bioactive compounds have been extracted, characterized and purified from various marine animals like tunicates, sponges, corals, and molluscs (Rajasekharan et al. 2011). Among cephalopods, the only studies involving bioactive peptides with antimicrobial activity (AMPs) are those conducted in squids and cuttlefish. They leave their eggs to fend for themselves and interestingly they do not get any infections. The eggs release polypeptides, sexual pheromones and AMPs trapped in the egg capsule, mainly expressed by female accessory sex gland that confers to them an efficient protection against microorganisms. Cephalopods, unlike other molluscs, have a closed circulatory system. The blood consists of haemolymph, haemocyanin and haemocytes (Novoa et al 2002). In this study we have focused the attention on the morphological and functional characterization of the haemocytes, from Octopus vulgaris, as the first responsible of the innate immunity. Three major haemocytes types were identified by light microscopy (hemoblast-like cells, hyalinocytes and granulocytes) based on nucleus/cytoplasm ratio and the presence or absence of cytoplasm granules. The haemocytes were cytochemically characterized for the presence of different activities responsible of the humoral response (phenoloxidase, peroxidise, phagocytosis). We have evaluated the bactericidal activity of haemocytes in the presence of different bacteria strains, using the method of the plate radial diffusion (Bauer et al 1996). We have also evaluated the activity of a methanolic acid extract of these cells, using the disc diffusion method and the minimum inhibitory concentration (MIC), in order to investigate the presence of soluble biotic compounds responsible of the antibacterial activity. Identifying the bioactive compounds could lead to many applications in fields such as halieutics and ecology (sexual pheromones), animal feeding (AMPs in pet food and aquaculture pellets), aquaculture and healthcare (AMPs).

Oestradiol plays in the mammalian brain crucial roles by modulating reproductive behaviour, neural plasticity and pain perception. The cephalopod Octopus vulgaris is considered, along with its relatives, the most behaviourally advanced invertebrate, although the neurophysiological basis of its behaviours including pain perception remain largely unknown. In the present study, using a combination of molecular and imaging techniques, we found that oestradiol up-regulated the Octopus vulgaris GnRH (Oct-GnRH) and Octopus vulgaris oestrogen receptor (Oct-ER) mRNA levels in the olfactory lobes, in turn Oct-ER mRNA was regulated by N-methyl-D-asparate (NMDA) in lobes involved in learning and motor coordination. Fluorescence Resonance Energy Transfer (FRET) analysis revealed that oestradiol binds Oct-ER causing conformational modifications and nuclear translocation consistent with the classical genomic mechanism of oestrogen receptor. Moreover oestradiol triggered a calcium influx and CREB (cyclic AMP response element binding protein) phosphorylation via membrane receptors, providing evidence for a rapid non-genomic action of oestradiol in Octopus vulgaris. In this paper we demonstrate, for the first time, the physiological role of oestradiol in the brain lobes of Octopus vulgaris involved in reproduction, learning and motor coordination.

I risultati ottenuti dimostrano, per la prima volta, una localizzazione citoplasmatica della PARP e suggeriscono la presenza dell'isoforma PARP2 nel SNC di L.stagnalis

The main results will be discussed in the light of a possible regulatory role played by PARP on actin polymerization/depolymerization in Octopus CNS

In this study we have focused the attention on the morphological and functional characterization of the haemocytes from Octopus vulgaris as the first responsible of the innate immunity. Three major haemocytes types were identified by light microscopy based on nucleus/cytoplasm ratio and the presence or absence of cytoplasm granules: haemoblast-like cells, hyalinocytes and granulocytes. The presence of three haemocyte populations was also confirmed by flow cytometry. A cytochemical characterization shows their different activities responsible of the humoral response. Using plate radial diffusion method we demonstrated the bactericidal activity of haemocytes in the presence of different bacteria strains. In order to investigate the presence of soluble biotic compounds responsible of the antibacterial activity, using disc diffusion method and the minimum inhibitory concentration, we have also tested the methanolic acid extract from these cells. Our results pave the way for the development of potent antibacterial drugs that could lead to many applications.

In this study we have investigated the role of 17beta-estradiol and progesterone in the reproduction of the crayfish Cherax albidus by using vitellogenin (VTG) as a biomarker. Early-vitellogenic (EV), full-vitellogenic (FV), and non-vitellogenic (NV) females of Cherax albidus were treated with 17beta-estradiol, progesterone, or both for 4 weeks. Levels of VTG mRNA in the hepatopancreas were detected by RT-PCR. The PCR product was sequenced and showed 97% homology with Cherax quadricarinatus VTG. 17beta-estradiol was more effective than progesterone and 17beta-estradiol plus progesterone in increasing the vitellogenin transcript in the hepatopancreas of EV and FV females. On the contrary, progesterone was more effective than 17beta-estradiol and 17beta-estradiol plus progesterone in increasing the vitellogenin concentration in the hemolymph of EV and FV females. Hepatopancreas histology and fatty acid composition of females injected with hormones showed major modifications. No effects were registered in NV females. In conclusion, 17beta-estradiol and progesterone influence VTG synthesis, although our data indicate that they act through different pathways and are not effective until the proper hormonal environment is established, as demonstrated by their inefficacy in NV females.

Recent investigation has focused on the participation of the poly (ADP-ribose) polymerase (PARP) reaction in the invertebrate central nervous system (CNS) during the process of long-term memory (LTM). In this paper, we characterize, localize, and assign a possible role to a cytoplasmic PARP in the brain of Octopus vulgaris. PARP activity was assayed in optic lobes, supraesophageal mass, and optic nerves. The highest levels of enzyme were found in the cytoplasmic fraction. Hyper-activation of the enzyme was detected in Octopus brain after visual discrimination training. Finally, cytoplasmic PARP was found to inhibit Octopus vulgaris actin polymerization. We propose that the cytoplasmic PARP plays a role in vivo to induce the cytoskeletonal reorganization that occurs during learning-induced neuronal plasticity.