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61.
Marina Ripamonti Silvana Canevari Sylvie Ménard Delia Mezzanzanica Silvia Miotti Rosaria Orlandi Franco Rilke Elda Tagliabue Maria Ines Colnaghi 《Cancer immunology, immunotherapy : CII》1987,24(1):13-18
Summary In order to investigate in vivo clinical applications of murine monoclonal antibodies directed against human ovarian carcinoma a preclinical in vivo model was developed using BALB/c athymic mice. Three human carcinoma cell lines (MCF7, HT29, and SW626) were injected into the peritoneal cavity of pristane-primed animals and the biological and antigenic characteristics of the i.p. grown tumors were studied. The animals were killed when moribund or 6–8 weeks after tumor injection. At autopsy tumor take was observed in 85% of the injected animals, whereas palpable nodules were evident in only 83%. Examination of the peritoneal cavity revealed intraabdominal carcinomatosis with tumor masses varying in size between 0.2 and 0.5 cm in diameter and tumor sheets. The most frequently affected organs were the diaphragm, the liver, and the reproductive system. Ascitic fluid formation was rare and no animal developed tumors outside the peritoneal cavity. To determine whether the in vivo tumors retained the same antigenic characteristics as the in vitro cell lines, four monoclonal antibodies (MBrl, MOv2, MOv8, and MOv15) directed against ovarian carcinoma-associated antigens and two different experimental approaches (immunofluorescence and immunoblotting) were used. Variations at either a quantitative or a qualitative level were observed for some antigens, whereas no evident changes were apparent for others. In particular, the antigens detected by MBr1 and MOv15 on the MCF7 line both maintained high levels of expression and immunoblotting staining pattern, whereas the antigens detected by MOv2 on the HT29 and SW626 lines, although present at a high level, clearly changed their staining pattern. As regards the antigens recognized by MOv8 and MOv15 on the HT29 and SW626 lines, we observed a drastic decrease in the level of their expression and in many cases a drop below the threshold of detectability of the test. The intraabdominal carcinomatosis described partially mimics the growth characteristics of human ovarian cancer and maintains the expression of some antigenic markers associated with epithelial tumors of the ovary and may therefore be useful in devising immunodiagnostic and/or immunotherapeutic strategies for ovarian carcinoma. 相似文献
62.
Maria Rosaria Barone Lumaga Mario Coiro Elisabeth Truernit Boglrka Erdei Paolo De Luca 《Botanical journal of the Linnean Society. Linnean Society of London》2015,179(2):236-254
The genus Dioon occupies an important phylogenetic position as sister to the other Zamiaceae. However, its epidermal morphology is still poorly known. We employed scanning and transmission electron microscopy, confocal microscopy and light microscopy to examine the epidermal and cuticular morphology of 12 of the 14 currently recognized species of Dioon, examining cultivated plants and herbarium specimens. Epidermal characters separate Dioon quite clearly from the other genera of the cycads. Within the genus, the major subgroups can be distinguished by their epidermal morphology. Some characters, such as the degree of stomatal protection, reflect ecological specializations in species within the subgroups. Several epidermal characters of the crown group Dioon seem to be absent in the Cenozoic fossils usually associated with the genus, which have been used as calibrations in many recent molecular dating analyses. The presence of similar characters in a Mesozoic fossil adapted to volcanic stress offers a new key in the interpretation of Dioon evolution. © 2015 The Linnean Society of London, Botanical Journal of the Linnean Society, 2015, 179 , 236–254. 相似文献
63.
To extend the model that explains why and how much absorption flattening (AF) influences circular dichroism (CD) signals, we have investigated the interesting case of exciton CD in the Soret region of a noncovalent complex formed by (Delta-RuPhen(3))(2+) and the tetraanionic porphyrin H(2)TPPS. Different concentrations have been studied by using an AF emulator and spectra simulation. The CD spectra of this compound occasionally show distortions in the solution sampling mode with the increase of concentration; the inhomogeneous distribution in the cell volume is due to aggregation and is the source of the AF effect. On the basis of these results, we conclude that AF is an important cause of distortions in CD spectra for Delta-RuPhen(3) . H(2)TPPS complexes and might affect the CD bands of other aggregated systems as well. 相似文献
64.
Pressure pain threshold of the cervico‐facial muscles in healthy elderly people: the role of gender,age and dominance 下载免费PDF全文
65.
Streptococcus agalactiae Capsule Polymer Length and Attachment Is Determined by the Proteins CpsABCD
66.
Dual target strategy: combining distinct non‐dopaminergic treatments reduces neuronal cell loss and synergistically modulates l‐DOPA‐induced rotational behavior in a rodent model of Parkinson's disease 下载免费PDF全文
Marie‐Therese Fuzzati‐Armentero Silvia Cerri Giovanna Levandis Giulia Ambrosi Elena Montepeloso Gianfilippo Antoninetti Fabio Blandini Younis Baqi Christa E. Müller Rosaria Volpini Giulia Costa Nicola Simola Annalisa Pinna 《Journal of neurochemistry》2015,134(4):740-747
The glutamate metabotropic receptor 5 (mGluR5) and the adenosine A2A receptor (A2AR) represent major non‐dopaminergic therapeutic targets in Parkinson's disease (PD) to improve motor symptoms and slow down/revert disease progression. The 6‐hydroxydopamine rat model of PD was used to determine/compare the neuroprotective and behavioral impacts of single and combined administration of one mGluR5 antagonist, 2‐methyl‐6‐(phenylethynyl)pyridine (MPEP), and two A2AR antagonists, (E)‐phosphoric acid mono‐[3‐[8‐[2‐(3‐methoxyphenyl)vinyl]‐7‐methyl‐2,6‐dioxo‐1‐prop‐2‐ynyl‐1,2,6,7‐tetrahydropurin‐3‐yl]propyl] (MSX‐3) and 8‐ethoxy‐9‐ethyladenine (ANR 94). Chronic treatment with MPEP or MSX‐3 alone, but not with ANR 94, reduced the toxin‐induced loss of dopaminergic neurons in the substantia nigra pars compacta. Combining MSX‐3 and MPEP further improved the neuroprotective effect of either antagonists. At the behavioral level, ANR 94 and MSX‐3 given alone significantly potentiated l ‐DOPA‐induced turning behavior. Combination of either A2AR antagonists with MPEP synergistically increased L‐DOPA‐induced turning. This effect was dose‐dependent and required subthreshold drug concentration, which per se had no motor stimulating effect. Our findings suggest that co‐treatment with A2AR and mGluR5 antagonists provides better therapeutic benefits than those produced by either drug alone. Our study sheds some light on the efficacy and advantages of combined non‐dopaminergic PD treatment using low drug concentration and establishes the basis for in‐depth studies to identify optimal doses at which these drugs reach highest efficacy.
67.
Rosaria VarìMassimo D'Archivio Carmelina FilesiSimona Carotenuto Beatrice ScazzocchioCarmela Santangelo Claudio GiovanniniRoberta Masella 《The Journal of nutritional biochemistry》2011,22(5):409-417
Protocatechuic acid (PCA) is a main metabolite of anthocyanins, whose daily intake is much higher than that of other polyphenols. PCA has biological effects, e.g., it induces the antioxidant/detoxifying enzyme gene expression. This study was aimed at defining the molecular mechanism responsible for PCA-induced over-expression of glutathione (GSH) peroxidase (GPx) and GSH reductase (GR) in J774 A.1 macrophages. New evidence is provided that PCA increases GPx and GR expression by inducing C-JUN NH2-terminal kinase (JNK)-mediated phosphorylation of Nuclear factor erythroid 2 (NF-E2)-related factor 2 (Nrf2). RNA and proteins were extracted from cells treated with PCA (25 μM) for different time points. Quantitative real-time polymerase chain reaction and immunoblotting analyses showed a rapid increase in mRNA (>60%) and protein (>50%) for both the enzymes. This was preceded by the up-regulation of Nrf2, in terms of mRNA and protein, and by its significant activation as assessed by increased Nrf2 phosphorylation and nuclear translocation (+60%). By using specific kinase inhibitors and detecting the activated form, we showed that JNK was the main upstream kinase responsible for Nrf2 activation. Convincing evidence is provided of a causal link between PCA-induced Nrf2 activation and increased enzyme expression. By silencing Nrf2 and using a JNK inhibitor, enzyme enhancement was counteracted. Finally, with the ChIP assay, we demonstrated that PCA-activated Nrf2 specifically bound ARE sequences in enzyme gene promoters. Our study demonstrates for the first time that PCA improves the macrophage endogenous antioxidant potential by a mechanism in which JNK-mediated Nrf2 activation plays an essential role. This knowledge could contribute to novel diet-based approaches aimed at counteracting oxidative injury by reinforcing endogenous defences. 相似文献
68.
Romagnoli R Baraldi PG Cruz-Lopez O Tolomeo M Di Cristina A Pipitone RM Grimaudo S Balzarini J Brancale A Hamel E 《Bioorganic & medicinal chemistry letters》2011,21(9):2746-2751
Microtubules are dynamic structures that play a crucial role in cellular division and are recognized as an important target for cancer therapy. In search of new compounds with strong antiproliferative activity and simple molecular structure, a new series of 2-amino-3-(3′,4′,5′-trimethoxybenzoyl)-5-(hetero)aryl ethynyl thiophene derivatives was prepared by the Sonogashira coupling reaction of the corresponding 5-bromothiophenes with several (hetero)aryl acetylenes. When these compounds were analyzed in vitro for their inhibition of cell proliferation, the 2- and 3-thiophenyl acetylene derivatives were the most powerful compounds, both of which exerted cytostatic effects at submicromolar concentrations. In contrast, the presence of a more flexible ethyl chain between the (hetero)aryl and the 5-position of the thiophene ring resulted in significant reduction in activity relative to the 5-(hetero)aryl acetylene substituted derivatives. The effects of a selected series of compounds on cell cycle progression correlated well with their strong antiproliferative activity and inhibition of tubulin polymerization. We found that the antiproliferative effects of the most active compounds were associated with increase of the proportion of cells in the G2/M and sub-G1 phases of the cell cycle. 相似文献
69.
García J Franci G Pereira R Benedetti R Nebbioso A Rodríguez-Barrios F Gronemeyer H Altucci L de Lera AR 《Bioorganic & medicinal chemistry》2011,19(12):3637-3649
A collection of analogues of the dimeric natural product psammaplin A that differ in the substitution on the (halo)tyrosine aryl ring, the oxime and the diamine connection has been synthesized. The effects on cell cycle, induction of differentiation and apoptosis of the natural-product inspired series were measured on the human leukaemia U937 cell line. Epigenetic profiling included induction of p21(WAF1), effects on global H3 histone and tubulin acetylation levels as well as in vitro enzymatic assays using HDAC1, DNMT1, DNMT3A, SIRT1 and a peptide domain with p300/CBP HAT activity. Whereas the derivatives of psammaplin A with modifications in the length of the connecting chain, the oxime bond and the disulfide unit showed lower potency, the analogues with changes on the bromotyrosine ring exhibited activities comparable to those of the parent compound in the inhibition of HDAC1 and in the induction of apoptosis. The lack of HDAC1 activity of analogues modified on the disulfide bond suggests that its cleavage must occur in cells to produce the monomeric Zn(2+)-chelating thiol. This assumption is consistent with the molecular modelling of the complex of psammaplin A thiol with h-HDAC8. Only a weak inhibition of DNMT1, DNMT3A and residual activities with SIRT1 and a p300/CBP HAT peptide were measured for these compounds. 相似文献
70.
Gitto R Damiano FM De Luca L Ferro S Vullo D Supuran CT Chimirri A 《Bioorganic & medicinal chemistry》2011,19(23):7003-7007
In a previous paper we identified several 1-aryl-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline-2-sulfonamides that displayed inhibitory effects toward selected carbonic anhydrase isozymes at micromolar concentration. In order to deepen the structure-activity relationships (SARs) and identify novel compounds with improved activity, we synthesized a series of monomethoxy analogues of the previously investigated dimethoxy derivatives. The evaluation of biological profile has been focused on in vitro effects against several CA isoforms. The new monomethoxy derivatives showed higher hCA inhibitory effects against several isoforms compared to the dimethoxy analogues. Particularly, some of these compounds (e.g., 1b and 1h) showed low nanomolar K(I) values and excellent selectivity for hCA IX and hCA XIV versus hCA I and II inhibition. 相似文献