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P Perego

Publications and source records attributed to P Perego.

At least 73 records · Page 4Linked to original sources

Effect of modulation of protein kinase C activity on cisplatin cytotoxicity in cisplatin-resistant and cisplatin-sensitive human osteosarcoma cells.

The effect of modulation of protein kinase C (PKC) activity by 12-O-tetradecanoylphorbol-13-acetate (TPA) on cisplatin cytotoxicity was examined in a human osteosarcoma U2-OS cell line and in a U2-OS variant (U2-OS/Pt) selected after continuous exposure to increasing concentrations of cisplatin. U2-OS/Pt cells showed a 7.5-fold resistance to the drug. A 24 h exposure of cells to TPA caused a potentiation of cisplatin cytotoxicity in sensitive and in resistant cells; under these conditions, PKC activity was shown to be down-regulated. In contrast, a short-term exposure of cells to TPA did not affect cisplatin cytotoxicity in U2-OS or in U2-OS/Pt cells. These results support the involvement of PKC in cellular response to cisplatin. However, this enzyme is probably not directly implicated in the mechanisms of acquired resistance in this cell system.

Cisplatin↗

Olive oil, corn oil, and n-3 fatty acids differently affect lipids, lipoproteins, platelets, and superoxide formation in type II hypercholesterolemia.

To evaluate which dietary fat may provide the best response in terms of plasma lipids and lipoproteins and also of platelet aggregability and superoxide formation by white blood cells, 12 type II patients were randomly allocated to three different diets, which provided polyunsaturated fatty acids (corn oil), monounsaturated fatty acids (olive oil), and a supplementation of ethyl esters of n-3 fatty acids to a prudent diet. Olive oil and, more significantly, n-3 ethyl esters lowered total cholesterol best (-2.2% and -5.8%, respectively); the latter diet, as expected, also significantly lowered triglyceridemia (-21.4%). The corn-oil diet exerted a small, statistically significant reduction of high-density-lipoprotein cholesterol (HDL) (-4.3%), and it also lowered plasma total apo B concentrations (-3.8%). n-3 ethyl esters significantly raised both total (+3.1%) and particularly HDL2 cholesterol (+24%). Platelet reactivity was insignificantly reduced by the three regimens, but all three significantly reduced thrombin-stimulated formation of thromboxane B2. Finally, only the n-3 fatty acid supplementation significantly reduced O2- generation by adherent monocytes. Dietary unsaturated fatty acids are generally effective on the plasma lipid and lipoproteins in type II patients, but significant differences may be found between the three tested regimens.

Apolipoproteins↗

Modulation of epidermal growth factor receptor tyrosine phosphorylation by tumor necrosis factor.

The effects of tumor necrosis factor (TNF) on epidermal growth factor (EGF) receptor tyrosine phosphorylation were investigated in Swiss 3T3 cells, which are sensitive to TNF action. At cytotoxic levels, TNF produced an appreciable inhibition of EGF-induced autophosphorylation of the receptor. A similar inhibition was detected even after prolonged treatment with 12-O-tetradecanoylphorbol-13-acetate (TPA) which produces down-regulation of protein kinase C (PKC). According to this finding, TNF does not induce phosphorylation of the 80 kDa PKC-specific substrate. These results support the hypothesis that the inhibition of EGF receptor tyrosine phosphorylation is not mediated via stimulation of PKC activity in intact Swiss 3T3 cells.

Animals↗

Protein kinase C activation by anthracyclines in Swiss 3T3 cells.

The effects of the anti-cancer anthracyclines doxorubicin and daunorubicin on the activity of protein kinase C (PKC) were examined in intact Swiss 3T3 cells. The 2 drugs stimulated the phosphorylation of an 80K phosphoprotein found to be identical to that generated in response to the PKC activator 12-O-tetradecanoylphorbol-13-acetate as indicated by gel electrophoresis and peptide mapping. The effect of doxorubicin was dose-dependent in the range 10(-5) to 10(-3) M and was not associated with a detectable translocation of PKC activity from cytosol to the cell membrane. Doxorubicin and daunorubicin were found to increase the incorporation of phosphate into phosphatidic acid, phosphatidylinositol 4-monophosphate and phosphatidyl inositol 4,5-bisphosphate. In addition, the anthracyclines induced a rise in inositol phosphates, thus indicating a stimulation of the breakdown of phosphoinositides. These data are consistent with an indirect mechanism of PKC activation by anthracyclines. We propose that diacylglycerol, which is derived from the hydrolysis of phospholipids, (including the phosphoinositides), by activation of phospholipases, could mediate PKC activation. The described effects, involving cell-signal-transducing pathways, emphasize a new aspect of the cellular actions of these anti-tumor agents.

Animals↗

Effect of tumor necrosis factor on human tumor cell lines sensitive and resistant to cytotoxic drugs, and its interaction with chemotherapeutic agents.

We investigated the cytotoxic effects of recombinant tumor necrosis factor (TNF) alone and in combination with interferon-gamma (IFN-gamma) and/or cytotoxic drugs on a variety of human tumor cell lines (U937, IGROV-1, HT29, LoVo, MCF7 and U20S), including cell lines with in vitro acquired resistance (LoVo/DX and MCF7/DX selected for resistance to doxorubicin (DX) and characterized by pleiotropic drug resistance; U20S selected for resistance to cisplatin (CDDP], using MTT assay. U937 and MCF7 were sensitive to the cytotoxic effect of TNF, whereas all the other cells were insensitive up to 1000 U/ml (the maximum tested dose). Surprisingly, TNF was cytotoxic (30-40% cytotoxicity) against two resistant lines (LoVo/DX and U20S/Pt) but not against the parent sensitive lines. Treatment with increasing doses of TNF after 6 h incubation with a subtoxic concentration of IFN-gamma produced a synergistic effect in four cell lines (U937, HT29, LoVo/DX and MCF7), whereas in the other five the cell killing of the combination was comparable with that achieved by TNF alone. The combination of subtoxic doses of TNF and increasing doses of drugs targeted at DNA topoisomerase II (i.e. DX, actinomycin D and VP16) produced an additive cytotoxic effect in all cell lines. The same results were obtained combining TNF and CDDP, except in U20S/Pt cells in which TNF synergistically increased CDDP cytotoxicity. The combination of TNF and IFN-gamma enhanced cytotoxicity about 20-fold for DX and 6-fold for CDDP, evaluated in terms of the modification index, against LoVo/DX and U20S/Pt cells respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Antineoplastic Agents↗

Transcultural differences in the perception of life events.

The perception of life events of Italian and English subjects was compared. Psychiatric patients and relatives rated 58 life events according to the degree to which the event was regarded as upsetting. The similarity between the two groups was noted, although Italian subjects tended to rate events as less upsetting than the English. The findings excluded that the rating differences between the two groups reflected differences in reaction to life and confirmed the existence of scaling similarity over national groups.

Adolescent↗

[Anastomosis in emergency large intestine resections in the therapy of obstructing colonic cancer].

A comparative inquiry has been performed on 57 cases of colonic resections for colon carcinoma carried out in emergency with intestinal anastomoses which have been performed according to Gambee's technique (single layer little introflecting suture), Nockemann's technique (a continuous suture in dexon comprising mucosal and submucosal layers and a separate no introflecting stitch suture of the serosal and mucosal layers in teflene) and 'Auf Stoss'-technique (single layered end-on, no introflecting, no mucosal comprising). We have noticed leakages in 20% of the cases performed with the first method, 13% with the second and 12% with the third method. Here below shown the reasons, why the second and the third method are to be considered the best ones and the indications relevant to their usage. Also are discussed: intraoperative irrigation of the colon according to Dudley and the own technique, short term chemotherapeutic prophylaxis, transanastomotic drain, fibrin glue on colon anastomosis.

Anti-Bacterial Agents↗

[Function of the pituitary-thyroid axis after partial resection of the thyroid].

The TSH, T4 and T3 responses to TRH were measured in 48 patients who underwent selective goitre resection (hemithyroidectomy, ablation of single nodule); moreover 3 groups of healthy, hypothyroid and hyperthyroid persons served as reference groups. The main object was to detect eventual onset of preclinical hypothyroidism. This condition was observed after hemithyroidectomy only in 12.5%, and never after ablation of single nodule. Were detected too, among operated patients, 2 subjects with light and 1 with clear hyperthyroidism. Therapeutic implications of such a finding were taken into consideration.

Adult↗