866 research outputs found

    Cytosolic phosphorylated EGFR is predictive of recurrence in early stage penile cancer patients: A retropective study

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    Background: Penile cancer (PC) is a rare tumor, and therapeutic options are limited for this disease, with an overall 5-year overall survival around 65-70%. Adjuvant therapy is not recommended for patients with N0-1 disease, despite up to 60% of these patients will die within 5 years from diagnosis. Methods: Medical records of all patients who underwent radical surgery at University Federico II of Naples and at National Tumor Institute "Pascale" of Naples for early squamous cell carcinoma of the penis from January, 2000 to December, 2011 were retrieved. Paraffin wax embedded tissue specimens were retrieved from the pathology archives of the participating Institutions for all patients. Expression of p-EGFR, EGFR and positivity to HPV were evaluated along with other histological variables of interest. Demographic data of eligible patients were retrieved along with clinical characteristics such as type of surgical operation, time of follow up, time of recurrence, overall survival. A multivariable model was constructed using a forward stepwise selection procedure. Results: Thirty eligible patients were identified. All patients were positive for EGFR by immunohistochemistry, while 13 and 16 were respectively positive for nuclear and cytosolic p-EGFR. No EGFR amplification was detected by FISH. Eight patients were positive for high-risk HPV by ISH. On univariable analysis, corpora cavernosa infiltration (OR 7.8; 95% CI = 0,8 to 75,6; P = 0,039) and positivity for cytosolic p-EGFR (OR 7.6; 95% CI = 1.49 to 50; P = 0.009) were predictive for recurrence, while only positivity for cytosolic p-EGFR (HR = 9.0; 95% CI 1.0-100; P = 0,0116) was prognostic for poor survival. Conclusion: It is of primary importance to identify patients with N0-1 disease who are at increased risk of recurrence, as they do not normally receive any adjuvant therapy. Expression of p-EGFR was found in this series to be strongly related to increase risk of recurrence and shorter overall survival. This finding is consistent with the role of p-EGFR in other solid malignancies. Integration of p-EGFR with classic prognostic factors and other histology markers should be pursued to establish optimal adjuvant therapy for N0-1 PC patients

    Broad-Spectrum Antiviral Therapeutics

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    Currently there are relatively few antiviral therapeutics, and most which do exist are highly pathogen-specific or have other disadvantages. We have developed a new broad-spectrum antiviral approach, dubbed Double-stranded RNA (dsRNA) Activated Caspase Oligomerizer (DRACO) that selectively induces apoptosis in cells containing viral dsRNA, rapidly killing infected cells without harming uninfected cells. We have created DRACOs and shown that they are nontoxic in 11 mammalian cell types and effective against 15 different viruses, including dengue flavivirus, Amapari and Tacaribe arenaviruses, Guama bunyavirus, and H1N1 influenza. We have also demonstrated that DRACOs can rescue mice challenged with H1N1 influenza. DRACOs have the potential to be effective therapeutics or prophylactics for numerous clinical and priority viruses, due to the broad-spectrum sensitivity of the dsRNA detection domain, the potent activity of the apoptosis induction domain, and the novel direct linkage between the two which viruses have never encountered.National Institute of Allergy and Infectious Diseases (U.S.) (grant AI057159)New England Regional Center of Excellence for Biodefense and Emerging Infectious DiseasesUnited States. Dept. of Defense (Director of Defense Research & Engineering)United States. Defense Threat Reduction AgencyUnited States. Defense Advanced Research Projects Agenc

    Antiproliferative and pro-apoptotic effects afforded by novel Src-kinase inhibitors in human neuroblastoma cells

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    <p>Abstract</p> <p>Background</p> <p>Neuroblastoma (NB) is the second most common solid malignancy of childhood that usually undergoes rapid progression with a poor prognosis upon metastasis. The Src-family tyrosine kinases (SFKs) are a group of proteins involved in cancer development and invasiveness that seem to play an important role in the NB carcinogenesis.</p> <p>Methods</p> <p>To determine cell proliferation, the growth rate was evaluated by both MTT test and cells counted. Analysis of DNA content was performed for the evaluation of the cell cycle and apoptosis. To characterize the mechanisms underlying the antiproliferative effects induced by SI 34, a novel pyrazolo-pyrimidine derivative provided with Src inhibitory activity, the involvement of some cellular pathways that are important for cell proliferation and survival was investigated by western blot assays. In particular, the contribution of cyclins, Src and ERK were examined. Finally, experiments of cell adhesion and invasiveness were performed.</p> <p>Results</p> <p>Treatment of SH-SY5Y human NB cells and CHP100 human neuroepithelioma (NE) cultures with three novel pyrazolo[3,4-<it>d</it>]pyrimidine derivatives, namely SI 34, SI 35 and SI 83, inhibits the cell proliferation in a time and concentration-dependent manner. The maximal effect was obtained after 72 hours incubation with SI 34 10 μM. Fluorescence microscopy experiments, flow cytometry analysis and determination of caspase-3 activity by fluorimetric assays showed that SI 34 induced SH-SY5Y apoptosis. Moreover, SI 34 determined cell cycle arrest at the G0/G1 phase, paralleled by a decreased expression of cyclin D1. Furthermore, our data indicate that SI 34 reduces the SH-SY5Y cells adhesion and invasiveness. Evidence that SI 34 inhibits the Src and the ERK-phosphorylation, suggests the mechanism through which it exerts its effects in SH-SY5Y cells.</p> <p>Conclusions</p> <p>Our study shows the ability of this pyrazolo-pyrimidine Src inhibitor in reducing the growth and the invasiveness of human NB cells, suggesting a promising role as novel drug in the treatment of neuroblastoma.</p

    Materials recovery from WEEE: current situation in Sicily.

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    The potential recovery of materials and energy in one year in Italy and in Sicily was estimated assuming that all WEEEs were gathered through the collection – treatment – disposal system implemented according to the rules in force. The embodied energy (EE) recovery associated to material recovery was also estimated, starting from standard values of EE and from yields declared for each component. Mass fractions composition for some categories of WEEE given by a facility in Catania agree with the national averages. Starting from data given by another facility - located in Siracusa - which processes all the five R categories (R1 to R5), potential mass and energy recovery was estimated for this plant. The results compared with national estimates lead to the conclusion that currently this plant contributes by 6% as mass and by 5% for EE recovery. National figures for potential energy recovery from WEEE shows that 10 670 GWh could be theoretically recovered, that is as much as the energy used for civil needs in Italy by two millions people / yr

    Stanja Jπ = 2+ i 0+, T = 0 8Be na energijama pobuđenja oko 20 MeV

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    The 7Li(d, αα)n reaction induced by deuterons of an incident energy of 7 MeV has been used to excite the 8Be nucleus in the region of excitation energy Ex of about 20 MeV. Each of the obtained αα coincidence spectra was fitted by an incoherent sum of the Jπ=2+ and 0+, T=0 8Be levels at Ex=20.1 and 20.2 MeV, respectively. The results show that the experimental data are well fitted when the G values deduced for these levels are 0.90 and 0.70 MeV, respectively.Reakcija 7Li (d, αα) n inducirana deuteronima energije 7 MeV je iskorištena za proučavanje jezgre 8Be na energijama pobuđenja Ex oko 20 MeV. Koincidentni αα spektri poravnani su nekoherentnim zbrojem stanja Jπ = 2 + na Ex = 20, 1 MeV i Jπ = 0+ na Ex = 20,2 MeV. Rezultati pokazuju da su eksperimentalni podaci najbolje opisani ako se za širine navedenih stanja uzmu vrijednosti 0,90 MeV odnosno 0, 70 Me V
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