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121.
Buzzi S Rubboli D Buzzi G Buzzi AM Morisi C Pironi F 《Cancer immunology, immunotherapy : CII》2004,53(11):1041-1048
Purpose: Many years ago, diphtheria toxin (DT) showed antitumor activity in mice and in humans, but it was unclear whether this depended on the toxicity of the molecule only or on its strong inflammatory-immunological property as well. To deal with this open question, we planned to treat a group of cancer patients with cross-reacting material 197 (CRM197). CRM197 is a nontoxic mutant of DT that shares the immunological properties of the native molecule and its ability to bind to heparin-binding epidermal growth factor (HB-EGF), the specific cell-membrane receptor for DT that is often overexpressed in cancer. Methods: 25 outpatients with various advanced tumors who were refractory to standard therapies (23 subjects) or had refused, in whole or in part, conventional therapies (2 subjects) were treated with CRM197 injected subcutaneously in the abdominal wall, on alternate days, for 6 days. Three different dosages (1.7, 2.6, or 3.5 mg/day) were used according to the patients degree of immunological reactivity to DT/CRM197 (none, moderate, or high). Results: After the first administration of CRM197, a significant increase in the number of circulating neutrophils and in the serum level of TNF- was detected. Toxicities were minimal. Only patients with delayed-type hypersensitivity to DT/CRM197 had irritating skin reactions in the injection sites and a flu-like syndrome with fever. Pharmacokinetics showed a mean peak concentration (12.7 ng/ml) 12 h after the first injection and a mean half-life of 18.1 h. There were two complete and one partial responses (metastatic breast carcinoma, neuroblastoma, and metastatic breast carcinoma) lasting 4, 45+, and 15 months, respectively. Six cases of stable disease, lasting from 1 to 15 months, were also recorded. Conclusions: CRM197 injected subcutaneously elicited an inflammatory-immunological reaction, caused tolerable toxicities, was absorbed to a good extent into the circulatory system, and exerted some degree of biological antitumor activity. A possible role of neutrophils and TNF- in the mode of action of the molecule is hypothesized. 相似文献
122.
Gaetano Granozzi Renzo Benoni Mario Acampora Silvio Aime Domencio Osella 《Inorganica chimica acta》1984,84(1):95-100
The electronic structure of H2M3(CO)9S clusters (M = Ru, Os) is discussed on the basis of their He I and He II excited gas-phase photoelectron spectra and on the basis of CNDO quantum mechanical calculations. The PE data clearly demonstrate the cleavage of two direct MM interactions by operation of the bridging hydrides, giving rise to three-center two-electron MHM levels. The μ3-S bonding mode has been described in detail and compared with previous results on related μ3-CY cluster derivatives. The CNDO results on Ru3(CO)9S=, HRu3(CO)9S? and H2Ru3(CO)9S indicate that the μ3-S—cluster interaction is mostly independent of the presence of the bridging hydrides. 相似文献
123.
The ability to visualize plasmid DNA entrapment in muscle cells undergoing an "in vivo" electroporation treatment was investigated on BALB/c mice using a 7-T magnetic resonance imaging (MRI) scanner using the paramagnetic Gd-DOTA-spd complex as imaging reporter. Gd-DOTA-spd bears a tripositively charged spermidine residue that yields a strong binding affinity toward the negatively charged DNA chain (6.4 kb, K(a) = 2.2 x 10(3) M(-1) for approximately 2500 +/- 500 binding sites). Cellular colocalization of Gd-DOTA-spd and plasmid DNA has been validated by histological analysis of excised treated muscle. In vivo MRI visualization of Gd-DOTA-spd distribution provides an excellent route to access the cellular entrapment of plasmid DNA upon applying an electroporation pulse. 相似文献
124.
125.
Scholz-Starke J De Angeli A Ferraretto C Paluzzi S Gambale F Carpaneto A 《FEBS letters》2004,576(3):449-454
Currents mediated by a slow vacuolar (SV) channel were recorded and characterized in vacuoles from cultured carrot cells. The carrot channel shows the typical functional characteristics reported for channels of the SV category previously identified in other plants, i.e., slow voltage-dependent activation kinetics, current activation favoured by cytosolic calcium and permeability to different monovalent cations. The carrot channel is strongly activated by cytosolic reducing agents (such as dithiothreitol, DTT, and glutathione, GSH) and has a peculiar dependence on cytosolic pH, which, in turn, is affected by the concentration of cytosolic reducing agents. Specifically, in 1 mM DTT or GSH the channel displayed a maximum conductance at neutral pH. The normalized conductance did not depend significantly on DTT concentration at acidic pH, while at alkaline pH the attenuation of the normalized conductance declines with increasing DTT concentration. Our results suggest two pH-titratable groups within the carrot SV channel, one of these depending on cysteine residues exposed to the cytosolic side of the vacuole. 相似文献
126.
Kim K Bu Y Jeong S Lim J Kwon Y Cha DS Kim J Jeon S Eun J Jeon H 《Bioscience, biotechnology, and biochemistry》2006,70(8):1821-1826
Abies koreana Wilson (A. koreana) is a shrub or broadly pyramidal evergreen tree endemic in the mountainous regions of South Korea. We obtained the essential oil (EO) from alpine needle leaves of A. koreana by the supercritical fluid extraction (SFE) method. EO was analyzed by gas chromatography-mass spectrometry (GC-MS), and 68 compounds were identified constituting 95.66% of the oil. The major components were elemol (11.17%), terpinen-4-ol (9.77%), sabinene (8.86%), 10(15)-cadien-4-ol (7.16%), alpha-terpineol (6.13%), alpha-pinene (6.07%) and gamma-terpinene (4.71%). To investigate the memory-enhancing effects, we conducted a passive avoidance test using a scopolamine (1 mg/kg, ip)-induced amnesia mouse model. A peritoneal injection of EO from A. koreana (100 mg/kg) showed a memory enhancing effect of 72.7% compared with the control. These results suggest that EO of A. koreana may be a useful therapeutic agent against such amnesia-inducing diseases as Alzheimer and vascular dementia. 相似文献
127.
Tosatto SC Giacometti GM Valle G Costantini P 《Biochemical and biophysical research communications》2006,339(1):277-283
Recently, a novel Fe-hydrogenase from a high rate of hydrogen producing Enterobacter cloacae strain IIT-BT08 was identified and partially characterized. This 147 residue protein was found to be much smaller than previously known Fe-hydrogenases, yet retaining a high catalytic activity. We predicted the structure of this protein and found it to be structurally similar to one of the two sub-domains containing the catalytic H-cluster so far jointly present in all other Fe-hydrogenases. This novel architecture allows a tentative explanation of protein function with the high rate of catalytic activity being due to a missing regulatory sub-domain, presumably allowing higher enzymatic activity at the cost of greater exposure to oxygen inactivation. This new insight may improve our understanding of the molecular and functional organization of other, more complex Fe-hydrogenases. 相似文献
128.
Orain D Ofner S Koller M Carcache DA Froestl W Allgeier H Rasetti V Nozulak J Mattes H Soldermann N Floersheim P Desrayaud S Kallen J Lingenhoehl K Urwyler S 《Bioorganic & medicinal chemistry letters》2012,22(2):996-999
A new set of quinazolinedione sulfonamide derivatives as competitive AMPA receptor antagonist with improved properties compared to 1 is disclosed. By modulating physico-chemical properties, compound 29 was identified with a low ED(50) of 5.5mg/kg in an animal model of anticonvulsant activity after oral dosage. 相似文献
129.
Iglesias-Bartolome R Patel V Cotrim A Leelahavanichkul K Molinolo AA Mitchell JB Gutkind JS 《Cell Stem Cell》2012,11(3):401-414
The integrity of the epidermis and mucosal epithelia is highly dependent on resident self-renewing stem cells, which makes them vulnerable to physical and chemical insults compromising the repopulating capacity of the epithelial stem cell compartment. This is frequently the case in cancer patients receiving radiation or chemotherapy, many of whom develop mucositis, a debilitating condition involving painful and deep mucosal ulcerations. Here, we show that inhibiting the mammalian target of rapamycin (mTOR) with rapamycin increases the clonogenic capacity of primary human oral keratinocytes and their resident self-renewing cells by preventing stem cell senescence. This protective effect of rapamycin is mediated by the increase in expression of?mitochondrial superoxide dismutase (MnSOD), and the consequent inhibition of ROS formation and oxidative stress. mTOR inhibition also protects from the loss of proliferative basal epithelial stem cells upon ionizing radiation in?vivo, thereby preserving the integrity of the oral mucosa and protecting from radiation-induced mucositis. 相似文献
130.
Galectin-4 is a carbohydrate-binding protein belonging to the galectin family. Here we provide novel evidence that galectin-4 is selectively expressed and secreted by intestinal epithelial cells and binds potently to activated peripheral and mucosal lamina propria T-cells at the CD3 epitope. The carbohydrate-dependent binding of galectin-4 at the CD3 epitope is fully functional and inhibited T cell activation, cycling and expansion. Galectin-4 induced apoptosis of activated peripheral and mucosal lamina propria T cells via calpain-, but not caspase-dependent, pathways. Providing further evidence for its important role in regulating T cell function, galectin-4 blockade by antisense oligonucleotides reduced TNF-alpha inhibitor induced T cell death. Furthermore, in T cells, galectin-4 reduced pro-inflammatory cytokine secretion including IL-17. In a model of experimental colitis, galectin-4 ameliorated mucosal inflammation, induced apoptosis of mucosal T-cells and decreased the secretion of pro-inflammatory cytokines. Our results show that galectin-4 plays a unique role in the intestine and assign a novel role of this protein in controlling intestinal inflammation by a selective induction of T cell apoptosis and cell cycle restriction. Conclusively, after defining its biological role, we propose Galectin-4 is a novel anti-inflammatory agent that could be therapeutically effective in diseases with a disturbed T cell expansion and apoptosis such as inflammatory bowel disease. 相似文献