Biomedical subjects

P Rocchi

Publications and source records attributed to P Rocchi.

At least 19 recordsLinked to original sources

PubMed2005

Molecular profile of androgen-independent prostate cancer xenograft LuCaP 23.1.

After castration or therapeutic hormone deprivation, most cancer of the prostate (CaP) cells develop androgen-independent (AI) growth. In this work, we studied the effect of androgen depletion (castration) on the growth of experimental model LuCaP 23.1 xenograft. A total of 101 nude mice were implanted and analysed for their growth profile before experimental period 1 (11 weeks) and after castration experimental period 2 (15 weeks). For specific periods, tumors were harvested and assessed for molecular marker expression specific for CaP. Taking into account tumor dynamic growth, prior to castration we found 37 fast growing (FG) tumors (948.9+/-76.9 mm3) and 63 slow growing (SG) tumors (229.6+/-18.4 mm3). Real-time quantitative RT-PCR showed that in comparison to SGs, FGs contained elevated expression of epidermal growth factor receptor type 1 (HER1), urokinase plasminogen activator (uPA), thymidine phosphorylase (TP) and thymidilate synthase (TS) mRNAs expression and low levels of 5alpha-reductase 2 (5alpha-R2) mRNA. After castration all FG tumors progressed rapidly (by 5 weeks) to AI growth (FG-P). In SG castrated tumors, 66% of tumors showed retarded progression (by 12 weeks) to AI (SG-P), whereas 34% responded to castration (SG-R). Molecular analysis demonstrated distinct molecular profiles integrating different pathways associated with AI progression. The progressive tumors FG-P, and some tumors of SG-P subgroup, presented significantly high levels of HER1, epidermal growth factor receptor type 2 (HER2), TS, uPA, TP, tumor necrosis factor superfamily member 6 (FAS) and peptidylglycine alpha-amidating mono-oxygenase (PAM) mRNA all of which correlated with androgen receptor (AR) mRNA. The second subgroup of SG-P tumors showed a high expression of the anti-apoptotic gene Bcl-2. A third subgroup of SG-P tumors showed significant expression of hypoxia-related genes such as adrenomedullin (AM) after castration. LuCaP 23.1 xenograft represent a useful dynamic model to study pre-clinically new therapeutic molecules and evaluate non-randomized therapeutics protocols combining different target inhibition specific to each AI pathways.

Adrenomedullin↗

PubMed2005

An additional performance of HTRS: the waste radiotoxicity minimisation.

The management of radioactive waste is a key issue for the present and future use of nuclear energy. In this frame, high temperature reactors (HTRs) have, among others, the capability to burn actinides. After a short introduction on HTRs, the performances of two MC-based burnup codes (Monte Carlo continuous energy burnup and MONTEBURNS) in assessing the ability of these reactors to burn actinides are compared. These codes are necessary for performing ultra-high burnup calculations on HTRs. The best one, in this specific case, results to be MONTEBURNS. It was analysed using HTRs loaded with the following: (1) 1st generation Pu, 600 equivalent full power days; (2) 2nd generation Pu, 645 equivalent full power days; and (iii) 33% 1st generation Pu and 67% Th, 705 equivalent full power days. Finally, it is possible to conclude that HTRs can reduce time when the waste is considered dangerous. Even if the amount of reduction does not solve the whole problem, it represents an important step in the management of radioactive waste.

Computer Simulation↗

PubMed2002

[Long term study on the efficacy and safety of lornoxicam in rheumatoid arthritis].

BACKGROUND: To assess the long term safety and therapeutic action of lornoxicam, a new non steroidal anti-inflammatory agent, in rheumatoid arthritis. METHODS: Open trial was carried out on different dosage schedules of lornoxicam (4 or 8 mg bid and 4mg tid) administered for six to twelve months. Patients of both sexes were enrolled, with classical or definite rheumatoid arthritis according to the A.R.A. criteria. RESULTS: Thirty-four patients (28 F, 6 M) were admitted, mean age (+/- SD) 53.9+/-14.2 years, mean duration of illness 9.2+/-10.7 years. Lornoxicam 8-16 mg/day showed good safety and therapeutic activity in long term treatment. Clinical improvement was limited, but progression of the disease was controlled. No adverse events were complained. CONCLUSIONS: Lornoxicam presented a worth-while therapeutic action and a good tolerability in rheumatoid arthritis long term treatment.

Adult↗

PubMed2001

Expression of adrenomedullin and peptide amidation activity in human prostate cancer and in human prostate cancer cell lines.

After therapeutic hormone deprivation, prostate cancer (CaP) cells often develop androgen-independent growth through not-well-defined mechanisms. The presence of neuroendocrine (NE) cells is often greater in prostate carcinoma than in normal prostate, and the frequency of NE cells correlates with tumor malignancy, loss of androgen sensitivity, increase of autocrine-paracrine activity, and poor prognosis. In some CaPs, neuropeptides have been previously implicated as growth factors. Peptidylglycine alpha-amidating monooxygenase (PAM) is the enzyme producing alpha-amidated bioactive peptides from their inactive glycine-extended precursors. In the present work, we demonstrate that androgen-independent PC-3 and DU145 cell lines, derived from human CaP, express PAM in vitro and in xenografts implanted in athymic nude mice, indicating that they are able to produce alpha-amidated peptides. Contrarily, barely detectable levels of PAM were found in the androgen-sensitive LNCaP cell line. We also show that whereas PC-3 and DU145 cells produce and secrete adrenomedullin (AM), a multifunctional amidated peptide, no expression was found in LNCaP cells. We further demonstrate that AM acts as a growth factor for DU145 cells, which suggests the existence of an autocrine loop mechanism that could potentially drive neoplastic growth. PAM mRNA levels were found to be 3-fold higher in prostate adenocarcinomas compared with that of human benign prostate hyperplasia (BPH) as demonstrated by real-time quantitative reverse transcription-PCR. The analysis of AM message expression in BPH and CaP (Gleason's score, 6-9) shows a clear distinction between benign and CaP. The expression was detected only in adenocarcinomas tissues with a marked increase in samples with a high Gleason's score. Immunocytochemically, AM was localized in the carcinomatous epithelial compartment. NE phenotype, assessed after the immunocytochemical localization of neuron-specific enolase (NSE), was found in both the epithelial and the stromal compartments of cancers; in BPH, only some spare basal cells were NSE-labeled. Cancer progression could be accelerated by peptides secreted by a population of cells capable of inducing androgen-independent tumoral growth via autocrine-paracrine mechanisms.

Adenocarcinoma↗

PubMed2000

Inhibitory activity of vitamin E and alpha-naphthoflavone on beta-carotene-enhanced transformation of BALB/c 3T3 cells by benzo(a)pyrene and cigarette-smoke condensate.

We previously found that beta-carotene (betaCT) can act as a co-carcinogenic agent enhancing the cell transforming activity of powerful carcinogens such as benzo(a)pyrene (B(a)P) and cigarette-smoke condensate (TAR) in an in vitro medium-term ( approximately 8 weeks) experimental model utilizing BALB/c 3T3 cells (Mutat. Res. 440 (1999) 83-90). Here, we investigated whether vitamin E (VitE) and alpha-naphthoflavone (alphaNF) are able to affect the co-carcinogenic activity of betaCT in terms of inhibiting B(a)P and TAR cell transforming potential. The following experimental schedules were performed: (i) cultures treated for 72 h with chemicals in various experimental combinations (acute treatment); (ii) cultures grown in presence of tester agents for the whole period of the assay (chronic treatment) to more closely mimic human exposure. While the co-carcinogenic potential of betaCT was confirmed on both B(a)P and TAR, the latter being ineffective by itself, we found in repeated experiments that the presence of VitE or alphaNF significantly reduced the betaCT's enhancing effect in the formation of transformation foci by B(a)P and TAR. The mechanism of the inhibition could be explained by the known ability of alphaNF to inhibit cytochrome P450-linked B(a)P-bioactivating monooxygenases, while VitE may contrast the prooxidant activity of betaCT (e.g., oxygen radicals overgeneration). While highlighting the importance of increasing knowledge of the role of single provitamins, vitamins and micronutrients, our findings also underline the potential advantages of combining several dietary supplements in in vitro preventive investigations.

3T3 Cells↗

PubMed2000

Characterization of carrot nuclear proteins that exhibit specific binding affinity towards conventional and non-conventional DNA methylation.

DNA methylation is associated with transcriptional silencing in vertebrates and plants. In mammals, the effects of methylation are mediated by a family of methyl-CpG-binding proteins. In plants the mechanisms by which methylation represses transcription are still not clear. In this paper we describe protein factors in carrot nuclear extracts exhibiting specific affinities for conventional or non-conventional methylation acceptor sites. We characterized two classes of proteins: the first, dcMBPI (Daucus carota methylated DNA-binding protein 1), shows high affinity for sequences containing 5-methylcytosine; the second, dcMBP2 (Daucus carota methylated DNA-binding protein 2), efficiently complexes sequences containing 5-methylcytosine in both CpXpX and CpXpG trinucleotides and shows much lower affinity for 5-methyl CpG dinucleotides. Both dcMBP1 and dcMBP2 are abundant proteins differing in molecular weight and binding features. Their activities are modulated during carrot vegetative cell growth and somatic embryo development. This is the first time that, in either plants or mammals, proteins exhibiting specific binding affinities for conventional or non-conventional DNA methylation have been shown. Based on these results, the possibility that both the extent and the context of the methylation might contribute to modulate gene expression is discussed.

5-Methylcytosine↗

PubMed1999

Age, testing at preferred or nonpreferred times (testing optimality), and false memory.

Two experiments investigated whether age and testing at preferred (optimal) times of day or nonpreferred (nonoptimal) times affected the ability to select relevant from irrelevant but thematically related alternatives in a verbal false memory paradigm. A 3rd experiment pursued the same issues with a visual false memory paradigm. In all 3 experiments, younger adults (n = 195) correctly recalled studied items more often than older adults (n = 121), whereas the 2 age groups correctly recognized about the same numbers of previously studied items. In all 3 experiments, nonoptimally tested older adults had more difficulty excluding nonstudied but thematically related items than the other groups; thus, they showed the greatest evidence of false memory, although all groups did so to a significant extent. The results suggest that optimality and its circadian determinants need to be considered with some tasks for the elderly. Various models and mechanisms are discussed.

Adolescent↗

PubMed1997

Cytotoxic and cell transforming activities of the fungicide methyl thiophanate on BALB/c 3T3 cells in vitro.

Cytotoxic and cell-transforming activities of methyl thiophanate a systemic fungicide capable of entering plant cells and thus controlling fungal diseases that have already started were studied in an in vitro medium-term (6-8 weeks) experimental model utilizing BALB/c 3T3 cells. Cells were exposed to the chemical, dissolved in dimethyl sulfoxide, in the absence or presence of an exogenous metabolizing system derived from rat livers supplemented with cofactors (S9 mix). In the absence of metabolic activation, methyl thiophanate exerted cytotoxic activity, evidenced through the formation of cell colonies, at low doses (> 10 micrograms/ml). However, the cytotoxic activity was greatly reduced by the S9 mix-induced metabolic activation of the chemical. Without bioactivation, cell-transforming potential, evidenced through the induction of transformation foci, was observable only at the highest (weakly toxic) dose employed (25 micrograms/ml). On the contrary, in the presence of metabolic activation, the cell-transforming activity was detectable at all tested doses (i.e. from 20 to 200 micrograms/ml) and it was particularly evident in a level-II transformation amplification test when the cells were allowed to perform active proliferative activity. These results, providing further information on the activity of methyl thiophanate in multistep carcinogenesis as possible genotoxic and/or co-carcinogenic agent, may contribute to better evaluate the oncogenic risk to man.

3T3 Cells↗

PubMed1997

Stem cell factor suppresses apoptosis in neuroblastoma cell lines.

Stem cell factor (SCF) is a glycoprotein growth factor produced by marrow stromal cells that acts after binding to its specific surface receptor, which is the protein encoded by the protooncogene c-kit. SCF synergizes with specific lineage factors in promoting the proliferation of primitive hematopoietic progenitors, and has been administered to expand the pool of these progenitors in cancer patients treated with high-dose chemotherapy. SCF and its c-kit receptor are expressed by some tumor cells, including myeloid leukemia, breast carcinoma, small cell lung carcinoma, melanoma, gynecological tumors, and testicular germ cell tumors. Previous studies of SCF in neuroblastoma have produced conflicting conclusions. To explore the role of SCF in neuroblastoma, we studied five neuroblastoma lines (IMR-5, SK-N-SH, SK-N-BE, AF8, and SJ-N-KP) and the neuroepithelioma line CHP-100. All lines expressed mRNA for c-kit and c-kit protein at low intensity as measured by flow cytometry, and secreted SCF in medium culture as shown by ELISA. Exogenous SCF did not modify 3H thymidine uptake in the neuroblastoma and neuroepithelioma cell lines. After 6 days' culture in the presence of anti-c-kit, the number of viable neuroblastoma cells was significantly lower than the control, and terminal deoxynucleotidyl transferase assay showed a substantial increase of apoptotic cells: The percentage of positive cells was 1-3% in the control lines, whereas in the presence of anti c-kit it varied from 29% of SK-N-BE to 92% of CHP-100. After 9 days' culture in the presence of anti-c-kit, no viable cells were detectable. These data indicate that SCF is produced by some neuroblastoma cell lines via an autocrine loop to protect them from apoptosis.

Antibodies, Monoclonal↗

PubMed1993

Processing capacity limitations in pictorial and spatial representations in the totally congenitally blind.

The study of visuo-spatial imagery abilities in totally congenitally blind people may be instrumental in understanding the contribution of visual experience to imagery processes. In the present paper visuo-spatial imagery capacity was explored through a task devised by Kerr (1987) and adapted for presentation to the blind, in which subjects were asked to imagine either two- or three-dimensional matrices of different complexity and to follow a mental pathway. The first experiment showed that blind people have difficulty with three-dimensional matrices which are within the reach of sighted people, and that their performance is affected by the processing rate. In the second experiment the spatial and pictorial components of visual imagery were analyzed by way of the same spatial task and of a pictorial-tactual task in which subjects had to match a mental representation of a pathway to a tactually explored wire silhouette. On the latter task, blind people did not meet any particular difficulty, probably because they could form representations using other sensory modalities and because they were skillful in tactual exploration. These data suggest that research on the blind cannot easily contribute to the distinction between the spatial and pictorial components of visual imagery.

Adolescent↗

PubMed1992

Induction of myogenic differentiation in human rhabdomyosarcoma cells by ionising radiation, N,N-dimethylformamide and their combination.

Differentiation-inducing ability of gamma-radiation, N,N-dimethylformamide and their combination has been tested on human rhabdomyosarcoma RMZ-RC2 clone cells. Ionising radiation at 2-5 Gy doses induced a more differentiated morphology, with the appearance of an increased proportion of multinuclear myotube-like cells, and a significant increase in myosin-positive and multinuclear cells. Radiation appeared to act by inducing de novo differentiated elements. N,N-dimethylformamide was able to induce an increased myosin expression, but did not affect multinuclear cell proportion. The combined treatment (ionising radiation and N,N-dimethylformamide) resulted in an additive increase in the proportion of myosin-positive cells, approaching 25-35%, but de novo differentiated elements were not increased above the levels obtained with irradiation alone.

Cell Differentiation↗

PubMed1990

Establishment and characterization of a primitive neuroectodermal tumor of bone continuous cell line (LAP-35).

A continuous tumor cell line (LAP-35) was established from a primitive neuroectodermal tumor of bone from the right tibia of a 12-year-old female. The neural character of the cell line was documented by the spontaneous growth of neurites and by the presence of several neural markers, including neuron-specific enolase (NSE), S-100 protein, neurofilaments, chromogranin A, synaptophysin and positivity to monoclonal antibodies UJ127.11, UJ13A, UJ181.4. Cell-sorter analysis showed a high expression of nerve growth factor receptor (NGFr) and major histocompatibility complex class I-related molecules. A unique cytogenetic profile was observed, including a reciprocal chromosomal translocation (rct) 11:22 (q24;q12), typically associated with Ewing's sarcoma and neuroepithelioma, and deletion of the short arm of chromosome 1 (lp-), otherwise a feature of neuroblastoma. N-myc proto-oncogene was neither amplified nor expressed, whereas the expression of c-myc was documented by northern blot analysis. These features distinguish this new cell line from previously reported neuroectodermal cell lines, identifying LAP-35 as a unique model of a group of neural bone tumors that share characteristics of neuroblastoma as well as neuroepithelioma.

Animals↗

PubMed1986

Effect of antioxidants on mutagenesis induced by DMBA in human cells.

The effect of vitamin A palmitate (VAP), vitamin A acetate (VAA), 2,3-tert-butyl-4-hydroxyanisole, and 2,6-di-tert-butyl-p-cresol (BHT) on mutagenesis induced by 7,12-dime-thylbenz[a]anthracene (DMBA) was examined in a human epithelial-like cell line. Cultures were exposed to DMBA with or without the antioxidant compound, and mutation frequencies were determined by selection against diphtheria toxin. A clear inhibition of mutagenesis was observed particularly with VAA and BHT.

9,10-Dimethyl-1,2-benzanthracene↗

PubMed1984

Polycystic ovarian disease: ultrasonic evaluation and correlations with clinical and hormonal data.

The size, shape, margins, and structure of the ovaries, as observed in 26 patients with polycystic ovarian disease were analyzed, and uterine/ovarian ratio (maximum antero-posterior diameter of uterine fundus divided for longitudinal diameter of ovary) was calculated. The maximum surface area of the organs ranged from 9.5 cm2 to 17.3 cm2 (average value 12.9 cm2). A "roundness index" (minimum diameter X 100/maximum diameter) was calculated in order to evaluate the shape: it ranged from a value of 100 in perfectly rounded ovaries to a value of 54 in ovaries of oval shape. The ovarian structure was characterized by many small cysts of the same dimensions in 19 cases; in two patients there was a predominant cyst; in five cases it appeared as many thick echoes arranged along parallel lines. The uterine/ovarian ratio was always equal to or less than 1. Correlation tests for size, shape of the ovaries, patient's age, and duration of symptoms were highly significant. This leads one to suppose that both of these ultrasonic findings are a function of the duration of the disease and that polycystic ovarian disease, once established, is the cause of progressive enlargement of these organs.

Adolescent↗

PubMed1983

Toxic, DNA-damaging and mutagenic activity of epichlorohydrin on human cells cultured in vitro.

Epichlorohydrin (ECHH) highly inhibited the tritiated thymidine uptake by human lymphocytes cultured in vitro, although the corresponding cell viability was unaffected. Furthermore, it elicited unscheduled DNA synthesis, acting as a DNA-damaging agent after its metabolic activation. ECHH also showed a clear toxic and mutagenic activity toward a human epithelial-like cell line, causing a decrease in cell viability and an increase in mutants resistant to 0.05 Lf/ml of diphtheria toxin.

Cell Line↗

PubMed1983

Induction of diphtheria toxin-resistant mutants in human cells by halogenated compounds.

The mutagenic power of 1,2-dichloroethane, 1,2-dibromoethane, 1,2-diiodoethane was tested in the human cell line, EUE. In our mutagenic system, based on selection against diphtheria toxin, the halogenated compounds, 1,2-dichloroethane and 1,2-dibromoethane revealed a strong mutagenic effect, whereas 1,2-diiodoethane was not mutagenic at a concentration allowing survival of 41%.

Cell Line↗

PubMed1983

Effect of vitamin A palmitate on mutagenesis induced by polycyclic aromatic hydrocarbons in human cells.

The effect of vitamin A palmitate (VAP) on mutagenesis induced by polycyclic aromatic hydrocarbons (PAH) was examined in a human epithelial-like cell line (EUE). Cultures were exposed to benzo[a]pyrene (BP), 3-methylcholanthrene (MCA), 7,12-dimethylbenz[a]anthracene, with or without VAP, and mutation frequencies were determined by selection against diphtheria toxin. A strong inhibition of mutagenesis was observed particularly with MCA and BP. VAP, in the same cell line, reduced 3H-labeled PAH binding to DNA.

9,10-Dimethyl-1,2-benzanthracene↗

PubMed1982

[Promoting action of tetradecanoylphorbol acetate on the phenotypic expression of the mutation for the acquisition of resistance to diphtheria toxin in cultured human cells].

Stable spontaneous mutants resistant to the protein synthesis inhibitor diphtheria toxin (DT) have been selected in human cell line eue at a very low frequency (8 x 10(-6)). We have studied in this system the effect of the promoting agent phorbol-12-myristate-13-acetate (TPA) on mutagenesis induced by benzo(a)pyrene (BP). TPA did not increase the mutation frequencies induced by BP, but it showed a trend to make shorter the expression time.

Benzo(a)pyrene↗