Activation of the Tumor Suppressor PP2A Emerges as a Potential Therapeutic Strategy for Treating Prostate Cancer     

Ion Cristóbal  Paula González-Alonso  Lina Daoud  Esther Solano  Blanca Torrejón  Rebeca Manso  Juan Madoz-Gúrpide  Federico Rojo  Jesús García-Foncillas 《Marine drugs》2015,13(6):3276-3286

Protein phosphatase 2A (PP2A) is a tumor suppressor complex that has recently been reported as a novel and highly relevant molecular target in prostate cancer (PCa). However, its potential therapeutic value remains to be fully clarified. We treated PC-3 and LNCaP cell lines with the PP2A activators forskolin and FTY720 alone or combined with the PP2A inhibitor okadaic acid. We examined PP2A activity, cell growth, prostasphere formation, levels of PP2A phosphorylation, CIP2A and SET expression, and AKT and ERK activation. Interestingly, both forskolin and FTY720 dephosphorylated and activated PP2A, impairing proliferation and prostasphere formation and inducing changes in AKT and ERK phosphorylation. Moreover, FTY720 led to reduced CIP2A levels. Treatment with okadaic acid impaired PP2A activation thus demonstrating the antitumoral PP2A-dependent mechanism of action of both forskolin and FTY720. Levels of PP2A phosphorylation together with SET and CIP2A protein expression were studied in 24 PCa patients and both were associated with high Gleason scores and presence of metastatic disease. Altogether, our results suggest that PP2A inhibition could be involved in PCa progression, and the use of PP2A-activating drugs might represent a novel alternative therapeutic strategy for treating PCa patients.  相似文献   

Effect of lime-induced leaf chlorosis on ochratoxin A, trans-resveratrol, and epsilon-viniferin production in grapevine (Vitis vinifera L.) berries infected by Aspergillus carbonarius     

Bavaresco L  Vezzulli S  Civardi S  Gatti M  Battilani P  Pietri A  Ferrari F 《Journal of agricultural and food chemistry》2008,56(6):2085-2089

Berries of Vitis vinifera L. cv. Merlot, grown on a neutral or calcareous soil, were infected, at phenological phases of veraison and ripening, by a conidial suspension of Aspergillus carbonarius to control ochratoxin A production and trans-resveratrol- and epsilon-viniferin-induced synthesis as affected by the soil lime content. Chlorosis occurrence was evaluated by a visual rating scale at veraison, and the leaves from vines growing on the calcareous soil showed the typical yellowing, whereas those grown on the neutral soil were dark green. Berry mineral element yield was recorded at veraison and ripening. Infection symptoms on berries were more severe at ripening in bunches collected from vines grown in calcareous soil. Ochratoxin A concentration increased at phenological phase of veraison in berries harvested from vines cultivated in calcareous soil. A. carbonarius enhanced trans-resveratrol and epsilon-viniferin production in infected berries more than in the control samples. Moreover, at veraison their concentration in the berries collected from vines grown in calcareous soil was greater than that recorded from berries collected from vines grown in the neutral soil. The lowest symptom severity was observed on berries containing the highest copper concentration.  相似文献   

Use of different geometric morphometrics tools for the discrimination of phenotypic stocks of the striped clam Ameghinomya antiqua (Veneridae) in north Patagonia,Argentina     

Federico Márquez  Jorgelina Robledo  Gabriela Escati Peñaloza  Silvina Van der Molen 《Fisheries Research》2010,101(1-2):127-131

The striped clam (Ameghinomya antiqua (King, 1832)) metapopulation of the San José Gulf is a good model for phenotypic stocks studies based on the shell shape variation in different fishing grounds. These sites show differences in circulation, tidal currents, coastal topography, and bathymetry. Furthermore, it is known that the diverse environments produce differences in the growth rate of this species. In the current work, we study the shell shape changes in the striped clam from different fishing grounds of the San José Gulf through geometric morphometrics methods. Outlines and landmarks analyses were successful to determinate the provenance of the individuals, with almost the 90% of correct assignations for the most of the fishing grounds. The different methodologies showed variations in diverse morphological traits, and as a result different patterns of the shell shape among localities were evidenced. Moreover, each site presented a typical shell shape. Our results showed that the geometric morphometrics methods are powerful tools to identify and separate intra-specific groups. This approach is applicable to other exploited species with subtle shape variations.  相似文献   

Evaluation of bilateral maxillary nerve block in dogs undergoing surgery for brachycephalic obstructive airway syndrome     

Chiara De Gennaro  Enzo Vettorato  Federico Corletto 《The Canadian veterinary journal. La revue veterinaire canadienne》2022,63(1):67

This retrospective study assessed the effect of an intraoral bilateral maxillary nerve block in dogs undergoing surgery for brachycephalic obstructive airway syndrome (BOAS). Records of dogs that underwent BOAS surgery were retrieved. Cases were assigned to Group B or C if a preoperative bilateral maxillary nerve block was performed or not. Type and dose of local anesthetic, inhalant anesthetic minimum alveolar concentration multiples, intraoperative fentanyl and injectable anesthetic use, prevalence of intraoperative hypotension or bradycardia, and postoperative opioids administration, were compared between groups. Sixty-seven cases met the inclusion criteria: 33 were assigned to Group B and 34 to Group C. In Group C, 18 dogs required intraoperative fentanyl (P = 0.005), and 12 needed injectable anesthetic top-ups (P = 0.006). Hypotension, or bradycardia, were not different between groups. Bilateral maxillary nerve block reduces intraoperative fentanyl and injectable anesthetic requirement in dogs undergoing BOAS surgery.  相似文献   

Characterization of fungicide sensitivity profiles of Botrytis cinerea populations sampled in Lombardy (Northern Italy) and implications for resistance management     

Silvia L Toffolatti  Giuseppe Russo  Davide Bezza  Piero A Bianco  Federico Massi  Demetrio Marcian  Giuliana Maddalena 《Pest management science》2020,76(6):2198-2207

  相似文献   

Volatile organic compounds (VOC) as biomarkers for detection of Ceratocystis platani     

Federico Brilli  Nicola Luchi  Marco Michelozzi  Luca Calamai  Gabriele Cencetti  Francesco Pecori  Emanuele Nigrone  Alberto Santini 《Forest Pathology》2020,50(4)

Ceratocystis platani causes canker stain of plane trees, and it represents a serious disease of Platanus spp. both in the United States and Europe. Current chemical or biological controls do not effectively manage C. platani, so new preventive methods need to be developed in order to limit this pathogen spreading. In this work, we have characterized the main volatile organic compounds (VOC) emitted in vitro from pure cultures of C. platani and other common pathogenic fungal species of hosts plants growing in the same ecosystems as plane trees. We found that C. platani emitted a similar blend of VOC compared with phylogenetically similar species C. populicola. In particular, C. platani was characterized by emission of isoamyl acetate and isobutyl acetate while C. populicola by ethyl acetate and isobutyl acetate, which were not released by any of the other out‐group fungal species grown on the same medium. Moreover, following a targeted approach based on the main VOC found in vitro, we have successfully validated in vivo that VOC uniquely emitted by C. platani (i.e. isobutyl acetate along with isoamyl alcohol) were released from the bark of plane trees following C. platani inoculation. Our results highlight the possibility to exploit VOC emitted specifically by C. platani as biomarkers to recognize Platanus x acerifolia plants infected by this pathogen.  相似文献   

The Potential Use of Mangrove Forests as Nitrogen Sinks of Shrimp Aquaculture Pond Effluents: The Role of Denitrification   总被引：4，自引：0，他引：4  

Victor H.  Rivera-Monroy Luis A.  Torres Nixon  Bahamon Federico  Newmark Robert R.  Twilley 《Journal of the World Aquaculture Society》1999,30(1):12-25

A generalized nitrogen budget was constructed to evaluate the potential role of mangrove sediments as a sink for dissolved inorganic nitrogen (DIN) in shrimp pond effluents. DIN concentrations were measured in pond effluents from three semi-intensive shrimp ponds along the Caribbean coast of Colombia between 1994–1995. Mean NH₄⁺ concentrations in the discharge water for all farms were significantly higher (67 × 12 μg/L) than in the adjacent estuaries (33 × 8 μg/L). Average NH₄⁺ concentrations in the pond discharge over all growout cycles were similar, representing an approximate doubling in relation to estuarine water concentrations. In contrast, NO₂^-+ NO₃^- concentrations were similar in both pond effluent and estuarine waters. Dissolved inorganic nitrogen loading of the ponds was similar. The estimated reduction of DIN in pond effluents by preliminary diversion of outflow to mangrove wetlands rather than directly to estuarine waters would be × 190 mg N/m² per d. Based on this nitrogen loss and depending upon the enrichment rate, between 0.04 to 0.12 ha of mangrove forest is required to completely remove the DIN load from effluents produced by a 1-ha pond.  相似文献   

Definition of the specificity of monoclonal antibodies against porcine CD45 and CD45R: report from the CD45/CD45R and CD44 subgroup of the Second International Swine CD Workshop     

Federico A. Zuckermann  Christina Peavey  William M. Schnitzlein  Daniel Schabacker  Robert J. Husmann  Huaizhi Yang  Armin Saalmü  ller  Joan K. Lunney 《Veterinary immunology and immunopathology》1998,60(3-4):367-387

Swine cell binding analyses of a set of 48 monoclonal antibodies (mAbs), including eleven standards, assigned to the CD44 and CD45 subset group of the Second International Swine CD Workshop yielded 13 clusters. Although none of these corresponded to CD44, seven mAbs formed a cluster which was identified as being specific for restricted epitopes of CD45 (CD45R). In addition, a T-cell subset specific cluster comprised of four mAbs was also identified. Two mAbs (STH106 and SwNL 554.1) reacted exclusively with CD8 bright lymphocytes, the other two (2B11 and F01G9) with a subset of CD4 lymphocytes. The other 10 clusters were either specific for MHC-class I like molecules or overlapped with clusters identified by the adhesion molecule subgroup and are therefore just briefly discussed in this report. The specificity of all the mAbs in the CD45R cluster was verified by their ability to immunoprecipitate distinct proteins and to react with CHO cells expressing individual isoforms of CD45. Three CD45R mAbs (3a56, MIL5, −a2) did react with a 210 kDa isoform(s), while another three (STH267, FG2F9, 6E3/7) only recognized a 226 kDa isoform(s). The remaining one (MAC326) precipitated both a 210 and 226 kDa protein. The specificity of all the mAbs in the CD45R cluster, and of the CD45 common mAbs, was confirmed by their reactivity with CHO cells transfected with cDNAs encoding the extracellular and transmembrane portions of distinct CD45R isoforms. Those mAbs recognizing a 210 kDa protein reacted with CHO cells expressing the CD45RC isoform, while those capable of precipitating a 226 kDa, but not the 210 kDa, polypeptide recognized CHO cells expressing either the CD45RAC and the relatively rare CD45RA isoform. MAC326 was unique in its inability to react with CHO cells engineered to produce the CD45RC and CD45RAC isoforms. Thus, three mAbs (6E3/7, STH267, and FG2F9) appear to be specific for an epitope(s) encoded by the A exon, while one (MAC326) recognizes a determinant encoded by the C exon. The remaining three mAbs (3a56, −a2, MIL5) are apparently specific for an epitope(s) which results from the fusion of the C exon to the invariant leader sequence and is destroyed by inclusion of the A exon. All three CD45 common mAbs, K252.1E4, MAC323 and 74.9.3, did react with the CHO cells lines expressing either the CD45RA, CD45RC, CD45RAC or CD45RO isoforms, but not with untransfected CHO cells. When the natural expression of CD45 isoforms was examined by reacting lymphocytes with CD45R mAbs, a high level expression of isoforms containing the A exon-generated domain was detected in all B cells while the majority of CD4⁺ T cells had undetectable or lower expression density of this protein than B cells. In contrast, the density of expression of the CD45 isoform(s) containing the C exon-generated domain ranged from undetectable to high in CD4⁺ T cells whereas the amounts were approximately ten-fold lower in B cells. Overall this panel of CD45 mAbs will be very useful in analyzing the maturation and differentiation of swine lymphoid cells subsets.  相似文献   

Angiogenic activity of swine granulosa cells: effects of hypoxia and vascular endothelial growth factor Trap R1R2, a VEGF blocker     

Bianco F  Basini G  Grasselli F 《Domestic animal endocrinology》2005,28(3):308-319

The possible role played by hypoxia and vascular endothelial growth factor (VEGF) in the regulation of follicular angiogenesis was studied in a three-dimensional fibrin gel model. Granulosa cells from follicles >5mm were subjected to normoxia (19% O2), partial (5% O2) or total (1% O2) hypoxia and their culture media were collected and used to stimulate porcine Aortic Endothelial Cells (AOC) included in the fibrin matrix. A suspension of AOC on microcarrier beads was pipetted in a fibrinogen solution (1 mg/ml PBS) before the addition of 1250 IU thrombine (250 microl) to catalize the gel formation. Granulosa cell conditioned media were tested in the presence or absence of VEGF Trap R1R2 (150 ng/ml), a potent VEGF inhibitor, that had its efficacy tested by adding VEGF (100 ng/ml) to AOC culture. Endothelial cell proliferation was measured at 48, 96, 144, 192 h by means of Scion Image Beta. A significant (p < 0.01) increase of AOC proliferation at each time of measurement was induced by culture media from granulosa cells subjected to partial (except at the end of the first 48 h) and total hypoxia compared to control and normoxia conditions, and by VEGF. VEGF Trap significantly (p < 0.01) inhibited the stimulatory effect of media conditioned by granulosa cells cultured in hypoxic conditions. These data suggest that hypoxia stimulates angiogenic activity of granulosa cells possibly by means of VEGF which could represent the main effector in promoting endothelial cell proliferation.  相似文献   

Sparing effect of a low dose of intrathecal morphine on fentanyl requirements during spinal surgery: a preliminary clinical investigation in dogs     

Novello L  Corletto F  Rabozzi R  Platt SR 《Veterinary surgery : VS》2008,37(2):153-160

Objective— To evaluate the effect of preoperative intrathecal administration of a low dose of morphine on intraoperative fentanyl requirements in dogs undergoing cervical and thoracolumbar spinal surgery.
Study Design— Prospective randomized clinical study.
Animals— Dogs (n=18) matched by surgical procedure administered intrathecal morphine (MG) or no-treatment (control group, CG).
Methods— After premedication with romifidine (4 μg/kg, intravenously) and induction with propofol, anesthesia was maintained with sevoflurane in oxygen. Intrathecal morphine 0.03 (0.023–0.034) mg/kg was administered at lumbar level 41 (25–65) minutes before surgery in MG. Ketamine (0.5 mg/kg) was administered hourly, starting before incision. Fentanyl infusion (1.2 and 4.2 μg/kg/h in MG and CG, respectively) was administered after a loading dose (5 and 10 μg/kg in MG and CG, respectively), and boluses were given if an increase >20% in heart rate and arterial blood pressure was observed. Total amount of fentanyl administered was recorded, to calculate hourly requirements and predict plasma concentration using a computer simulation.
Results— Hourly fentanyl consumption and predicted plasma concentrations at the time of response to surgery were significantly lower in MG compared with CG.
Conclusions— Preoperative administration of a low dose of intrathecal morphine has a sparing effect on intraoperative fentanyl requirements.
Clinical Relevance— Preoperative intrathecal administration of a low dose of morphine at the lumbar level represented a safe and effective mean of providing intraoperative analgesia in dogs undergoing cervical and thoracolumbar spinal surgery.  相似文献