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Koutsilieris M Mitsiades C Lembessis P Sourla A 《Journal of musculoskeletal & neuronal interactions》2000,1(1):15-17
It is a long-standing clinical observation that the bone corresponds to the prevalent site for metastatic growth of prostate cancer. In addition, bone metastases of this malignancy produce a potent blastic reaction, in contrast to the overwhelming majority of other osteotropic neoplasms, whose metastases are generally associated with an osteolytic reaction. Osteoblastic metastases represent almost always the first and, frequently, the exclusive site of disease progression to hormone refractory stage, stage D3. Moreover, the number of skeletal metastatic foci is the most powerful independent prognostic factor associated with a limited response to hormone ablation therapy and poor survival of advanced prostate cancer. It is noteworthy that disease progression to hormone refractory stage occurs almost always in osteoblastic metastases. These clinical observations suggested that the osteoblastic reaction is possibly not an innocent bystander of the metastatic prostate tumour growth, simply suffering its consequences, but it may in fact facilitate the efforts of metastatic cells to expand their population. An extensive line of research in the pathophysiology of osteoblastic metastases has established that the local blastic reaction involves the uPA/plasmin/IGF/IGFBP-3/TGFbs bioregulation system which can stimulate both the growth of osteoblasts and prostate cancer cells. Furthermore, we were the first to characterize osteoblast-derived 'survival factors' able to rescue metastatic prostate cancer cells from chemotherapy-induced apoptosis. These data resulted in the development of a novel concept of an anti-survival factor therapy, namely an anti-IGF-1 therapy, which has provided encouraging preliminary data in a phase II clinical trial with terminally-ill hormone/chemotherapy-resistant prostate cancer patients. 相似文献
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A wide-ranging examination of plastid (pt)DNA sequence homologies within
higher plant nuclear genomes (promiscuous DNA) was undertaken. Digestion
with methylation-sensitive restriction enzymes and Southern analysis was
used to distinguish plastid and nuclear DNA in order to assess the extent
of variability of promiscuous sequences within and between plant species.
Some species, such as Gossypium hirsutum (cotton), Nicotiana tabacum
(tobacco), and Chenopodium quinoa, showed homogenity of these sequences,
while intraspecific sequence variation was observed among different
cultivars of Pisum sativum (pea), Hordeum vulgare (barley), and Triticum
aestivum (wheat). Hypervariability of plastid sequence homologies was
identified in the nuclear genomes of Spinacea oleracea (spinach) and Beta
vulgaris (beet), in which individual plants were shown to possess a unique
spectrum of nuclear sequences with ptDNA homology. This hypervariability
apparently extended to somatic variation in B. vulgaris. No sequences with
ptDNA homology were identified by this method in the nuclear genome of
Arabidopsis thaliana.
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A survey was conducted to determine the levels of fumonisins B1 and B2 in corn and corn-based products available in Colombia
for human and animal consumption. A total of 120 samples were analyzed by acetonitrile-water extraction, cleanup with a strong-anion-exchange
column, and liquid chromatography with o-phthaldialdehyde-2-mercaptoethanol derivatization and fluorescence detection. The
samples of corn and corn-based products for animal intake were taken at different feed manufacturing plants, whereas the samples
used for human foods where purchased from local retail stores. The number of positive samples for fumonisin B1 was 20.0% higher
in corn and corn-based products for animal intake (75.0%) than in corn and corn-based products for human consumption (55.0%).
The levels of fumonisin B1 were also higher in corn and corn-based products for animal intake (mean = 694 μg/kg; range = 32–2964
μg/kg), than in corn and corn-based products for human intake (mean = 218 μg/kg; range = 24–2170 μg/ kg). The incidence and
levels of fumonisin B2 were lower than those for fumonisin B1. Corn and corn-based products for animal consumption had an
incidence of fumonisin B2 of 58.3%, with a mean value of 283 μg/kg, and a range of 44–987 μg/kg. The incidence of fumonisin
B2 in corn-based products for human intake was 35.0%, with a mean value of 118 μg/kg and a range of 21–833 μg/kg. The highest
incidence and levels of fumonisins were found in samples of hominy feed, with concentrations ranging from 86 to 2964 μg/kg
fumonisin B1 and 57 to 987 μg/kg fumonisin B2. 相似文献
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Phenotypic and functional effects of heat shock protein 90 inhibition on dendritic cell 总被引:1,自引:0,他引:1
Bae J Mitsiades C Tai YT Bertheau R Shammas M Batchu RB Li C Catley L Prabhala R Anderson KC Munshi NC 《Journal of immunology (Baltimore, Md. : 1950)》2007,178(12):7730-7737
The 90-kDa heat shock protein (Hsp90) plays an important role in conformational regulation of cellular proteins and thereby cellular signaling and function. As Hsp90 is considered a key component of immune function and its inhibition has become an important target for cancer therapy, we here evaluated the role of Hsp90 in human dendritic cell (DC) phenotype and function. Hsp90 inhibition significantly decreased cell surface expression of costimulatory (CD40, CD80, CD86), maturation (CD83), and MHC (HLA-A, B, C and HLA-DP, DQ, DR) markers in immature DC and mature DC and was associated with down-regulation of both RNA and intracellular protein expression. Importantly, Hsp90 inhibition significantly inhibited DC function. It decreased Ag uptake, processing, and presentation by immature DC, leading to reduced T cell proliferation in response to tetanus toxoid as a recall Ag. It also decreased the ability of mature DC to present Ag to T cells and secrete IL-12 as well as induce IFN-gamma secretion by allogeneic T cells. These data therefore demonstrate that Hsp90-mediated protein folding is required for DC function and, conversely, Hsp90 inhibition disrupts the DC function of significant relevance in the setting of clinical trials evaluating novel Hsp90 inhibitor therapy in cancer. 相似文献
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ERVĪNS LUKŠEVIČS PER E. AHLBERG ĢIRTS STINKULIS JEĻENA VASIĻKOVA IVARS ZUPIŅŠ 《Lethaia: An International Journal of Palaeontology and Stratigraphy》2012,45(3):356-370
Luk?evi?s, E., Ahlberg, P.E., Stinkulis, ?., Vasi?kova, J. & Zupi??, I. 2011: Frasnian vertebrate taphonomy and sedimentology of macrofossil concentrations from the Langsēde Cliff, Latvia. Lethaia, Vol. 45, pp. 356–370. The siliciclastic sequence of the Upper Devonian of Kurzeme, Western Latvia, is renowned for abundant vertebrate fossils, including the stem tetrapods Obruchevichthys gracilis and Ventastega curonica. During the first detailed taphonomic study of the vertebrate assemblage from the Ogre Formation cropping out at the Langsēde Cliff, Imula River, abundant vertebrate remains have been examined and identified as belonging to one psammosteid, two acanthodian and three sarcopterygian genera; the placoderm Bothriolepis maxima dominates the assemblage. Besides fully disarticulated placoderm and psammosteid plates, separate sarcopterygian scales and teeth, and acanthodian spines, partly articulated specimens including complete distal segments of Bothriolepis pectoral fins, Bothriolepis head shields and sarcopterygian lower jaws have been found. The size distribution of the placoderm bones demonstrates that the individuals within the assemblage are of approximately uniform age. Distinct zones have been traced within the horizontal distribution of the bones. These linear zones are almost perpendicular to the dominant dip azimuth of the cross‐beds and ripple‐laminae and most probably correspond to the depressions between subaqueous dunes. Concavity ratio varies significantly within the excavation area. The degree of fragmentation of the bones and disarticulation of the skeletons suggest that the carcasses were reworked and slightly transported before burial. Sedimentological data suggest deposition in a shallow marine environment under the influence of rapid currents. The fossiliferous bed consists of a basal bone conglomerate covered by a cross‐stratified sandstone with mud drapes, which is in turn overlain by ripple laminated sandstone, indicating the bones were buried by the gradual infilling of a tidal channel. All the Middle–Upper Devonian vertebrate bone‐beds from Latvia are associated with sandy to clayey deposits and have been formed in a sea‐coastal zone during rapid sedimentation episodes, but differ in fossil abundance and degree of preservation. □Agnathans, Devonian, facies analysis, fish, fossil assemblage, palaeoenvironment. 相似文献
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Thomas G Kristensen Jesper Nielsen Christian NS Pedersen 《Algorithms for molecular biology : AMB》2010,5(1):9
Background
The fingerprint of a molecule is a bitstring based on its structure, constructed such that structurally similar molecules will have similar fingerprints. Molecular fingerprints can be used in an initial phase of drug development for identifying novel drug candidates by screening large databases for molecules with fingerprints similar to a query fingerprint. 相似文献10.
Thomas Mailund Gerth S Brodal Rolf Fagerberg Christian NS Pedersen Derek Phillips 《BMC bioinformatics》2006,7(1):29-8