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Epigenetic modulation of PTEN expression during antiandrogenic therapies in human prostate cancer.
No full textAlthough the tumor-suppressor phosphatase and tensin homolog deleted on chromosome 10 (PTEN) is frequently mutated or deleted in a wide variety of solid tumors, some malignancies, including prostate cancer, exhibit undetectable PTEN protein without loss of PTEN gene. Aim of this study was to evaluate whether the PTEN downmodulation, observed during bicalutamide treatment, was due to epigentic events. We analyzed the expression of PTEN in presence or absence of azacitidine or valproic acid in a panel of 50 primary cultures derived from naive (UNT, 23 ptz) and bicalutamide-based neoadjuvant hormone therapy-treated patients (NHT, 27 pts). Results showed that Western blot and PCR analyses showed that 54 and 68% of primary cultures displayed detectable amounts of PTEN protein and mRNA, respectively. Treatment with azacitidine increased the percentage of PTEN-positive cultures up to 72 and 80% for PTEN protein and mRNA determination, respectively. Treatment with valproic acid was able to increase the percentage of PTEN-positive cultures up to 80 and 74% for PTEN protein and mRNA determination, respectively. The percentage of cultures with undetectable levels of PTEN protein was significatively higher in cultures derived NHT patients respect to cultures derived from UNT men (P=0.020). Valproic acid reduced significantly the percentage of cultures PTEN-negative only at protein level and only in NHT (P=0.029) group. In conclusion, our data suggests that antiandrogenic therapy reduced PTEN expression by epigenetic mechanisms suggesting that epigenetic drugs, upmodulating PTEN expression, can reduce Akt activity and probably enhance the efficacy of antiandrogenic therapy
IL-2-activated rat NK cells express inducible nitric oxide synthase that contributes to cytotoxic function and IFN-g production
No full textNatural killer (NK) cells are large granular lymphocytes capable of destroying cells infected by virus or bacteria and susceptible tumor cells without prior sensitization and restriction by major histocompatability complex (MHC) antigens, Their cytotoxic activity could be strongly enhanced by interleukin-2 (IL-2), Previous findings, even if obtained with indirect experimental approaches, have suggested a possible involvement of the inducible nitric oxide (iNOS) pathway in the NK-mediated target cell killing. The aim of the present study was first to directly examine the induction of iNOS in IL-2-activated rat NK cells isolated from peripheral blood (PB-NK) or spleen (S-NK), and second to investigate the involvement of the iNOS-derived NO in the cytotoxic function of these cells. Our findings clearly indicate the induction of iNOS expression in IL-2-activated PB-NK and S-NK cells, as evaluated either at mRNA and protein levels. Accordingly, significantly high levels of iNOS activity were shown, as detected by the L-arginine to L-citrulline conversion in appropriate assay conditions. The consequent NO generation appears to partially account for NK cell-mediated DNA fragmentation and lysis of sensitive tumor target cells, In fact, functional inhibition of iNOS through specific inhibitors, as well as the almost complete abrogation of its expression through a specific iNOS mRNA oligodeoxynucleotide antisense, significantly reduced the lytic activity of IL-2-activated NK cells. Moreover, IL-2-induced interferon-gamma production appears also to be dependent at least in part, on iNOS induction, (C) 1999 by The American Society of Hematolog
Imipenem reaches therapeutic concentrations in aqueous humor, as determined by HPLC
No full textThe majority of ocular infections in the industrialized countries arise after surgical interventions. An appropriate antibacterial prophylaxis is therefore highly desirable in eye surgery. We used high performance liquid chromatography (HPLC) to measure the concentrations reached by imipenem, a modern wide-spectrum beta-lactam antibiotic, in plasma and aqueous humor of 26 patients scheduled for cataract surgery. Even a single 500 mg dose of imipenem achieved therapeutic levels of the molecule for the most common ophthalmic pathogens (1 microgram/ml or above) in the aqueous humor within one to two hours after administration. This drug may therefore be suitable for antibacterial prophylaxis in eye surgery
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Interleukin-2-activated rat natural killer cells express inducible nitric oxide synthase that contributes to cytotoxic function and interferon-gamma production
No full textStatistical modelling of serum parameters in predicting histological liver damage in chronic hepatitis C
No full textErk-dependent cytosolic phospholipase activity is induced by cd95 ligand cross-linking in the mouse derived Sertoli cell line TM4 and is required to trigger apoptosis in CD95 bearing cells
No full textIn the present study we demonstrated that CD95L crosslinking generated reverse signalling in the mouse derived Sertoli cell line TM4, Treatment of TM4 cells with mAb anti-CD95L induced activation of the cytosolic phospholipase A(2) (cPLA(2)), Cytosolic PLA, activation was controlled by the MAPK pathway as indicated by the ability of the specific MEK inhibitor, PD098059, to abolish cPLA2 activation, In addition, Western blot experiments showed a rapid increase in phosphorylated Erk1/2 following CD95L cross-linking, while no effect on the phosphorylation of other MAPK, p38 or JNK, was observed, CD95L cross-linking by mAb increased the levels of soluble CD95L and apoptotic activity of TM4 cell supernatants, which was blacked by co-incubation with the PLA, inhibitor, AACOCF3 or PD098059, Finally, pre-treatment of TM4 cells with AACOCF(3) or PD098059 completely abolished TM4-induced apoptosis of Jurkat T cells, thus indicating that the Erk/cPLA(2) pathway is required for CD95L-induced apoptosis
HISTONE DEACETYLASE INHIBITOR, ROMIDEPSIN (FK228) IMPROVES ANTITUMOR EFFECTS OF DOCETAXEL AND CISPLATIN IN MODELS OF AGGRESSIVE PROSTATE CANCER
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