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51.
52.
Tenta R Sotiriou E Pitulis N Thyphronitis G Koutsilieris M 《Journal of musculoskeletal & neuronal interactions》2005,5(2):135-144
The development of resistance to anti-cancer therapies in bones is a major hurdle preventing long-lasting clinical responses to anti-cancer therapies in hormone refractory prostate cancer. Herein, we present the major signal transduction pathways, which are activated in prostate cancer cells residing at bone metastasis microenvironment. These intracellular signal transduction pathways can inhibit anti-cancer therapy-induced apoptosis of metastatic prostate cancer cells, thereby optimizing their survival, locally. Employment of this knowledge in a clinical setting provides the conceptual framework for the development of bone-targeted therapies for advanced prostate cancer. Indeed, bone metastasis microenvironment-targeted therapies illustrate a novel paradigm in cancer treatment: anti-tumor treatment strategies may not only aim at directly inducing cancer cell apoptosis, but can also target the tumor metastasis microenvironment, and neutralize the protection it confers on metastatic cancer cells. 相似文献
53.
The respiratory sensation and some routine cardiorespiratory parameters were studied on native Highlanders from the Argentine
Andes and on Lowlanders from Europe, already tested during previous high altitude expeditions. The tests were performed at
various altitude levels from 2688m e.i., the village altitude for Highlanders, to 5600m during an expedition to Mt. Aconcagua
(6990m). At rest, the perception of 4 external inspiratory resistive loads (ranged between 2.5 and 13 cm.H2O.L-1.s) can allow
us to fix by discrimination the sensitivity index P(A) independently of response bias (B) according to Sensory Decision Theory
(SDT). The Andean highlanders did not experience the respiratory sensation at the same limits as the European lowlanders well
adaptated to high altitude. At higher altitudes than their village altitude, their respiratory sensation presented a lower
threshold of perception and a weaker discrimination which might be partly explained by the evolution of some parameters of
their cardio-respiratory function when altitude increased. Indeed, in response to high altitude hypoxia (5600m), they increased
their respiratory frequency and not their minuteventilation or mouth pressure. This chosen ventilatory pattern was opposite
to the one chosen by the Lowlanders and did not allow for sufficient adaptation to a more important altitude hypoxia than
that of their village altitude. In conclusion, the Andean highlanders wellbeing adapted to their village altitude, exhibited
a difficult acclimatization to higher altitudes which might be due to the characteristics of their respiratory sensation.
These results might explain their weak physical performances during ascent to the Mt. Aconcagua summit in spite of special
training. 相似文献
54.
Variant forms of a group I intron in nuclear small-subunit rRNA genes of the marine red alga Porphyra spiralis var. amplifolia 总被引:3,自引:0,他引:3
A group IC1 intron occurs in nuclear small-subunit (18S) ribosomal RNA (SSU
rRNA) genes of the marine red alga Porphyra spiralis var. amplifolia. This
intron occurs at the same position as the self- splicing group IC1 introns
in nuclear SSU rDNAs of the fungus Pneumocystis carinii and in the green
alga Chlorella ellipsoidea and shares sequence identity with the
Pneumocystis carinii intron in domains L1, P1, P2, and L2, outside the
conserved core. Three size variants, differing in amount of sequence in L1,
exist and are differentially distributed in geographically distinct
populations. Preliminary data suggest that the largest variant can
self-splice in vitro. Short open reading frames are present but do not
correspond to known genes. Repeated nucleotide motifs, reminiscent of
duplicated target sites of transposons or Alu elements, are associated with
the intron and with one of the variant forms of L1. Insertions are present
in nuclear SSU rDNAs of several other Porphyra species and of the red alga
Bangia atropurpurea; insertionless rDNA variants also occur in several
Porphyra species. Our observations are most readily explained by intron
mobility, although it remains unclear how transfer could have been mediated
between genomes of organisms as ecologically diverse as marine red algae,
freshwater green algae, and a mammalian-pathogenic fungus.
相似文献
55.
Ingrid M L?nnstedt Franco Caramia Jason Li Debora Fumagalli Roberto Salgado Andrew Rowan Max Salm Nnennaya Kanu Peter Savas Stuart Horswell Stephan Gade Sibylle Loibl Patrick Neven Christos Sotiriou Charles Swanton Sherene Loi Terence P Speed 《Genome biology》2014,15(9)
Intra-tumor heterogeneity concerns the existence of genetically different subclones within the same tumor. Single sample quantification of heterogeneity relies on precise determination of chromosomal copy numbers throughout the genome, and an assessment of whether identified mutation variant allele fractions match clonal or subclonal copy numbers. We discuss these issues using data from SNP arrays, whole exome sequencing and pathologist purity estimates on several breast cancers characterized by ERBB2 amplification. We show that chromosomal copy numbers can only be estimated from SNP array signals or sequencing depths for subclonal tumor samples with simple subclonal architectures under certain assumptions.
Electronic supplementary material
The online version of this article (doi:10.1186/s13059-014-0470-7) contains supplementary material, which is available to authorized users. 相似文献56.
57.
58.
59.
Ferry Cornelissen Adriana MC Mus Patrick S Asmawidjaja Jan Piet van Hamburg Joel Tocker Erik Lubberts 《Arthritis research & therapy》2009,11(6):1-13
Introduction
A protein analysis using a mass spectrometry indicated that there are serum proteins showing significant quantitative changes after the administration of infliximab. Among them, connective tissue growth factor (CTGF) seems to be related to the pathogenesis of rheumatoid arthritis (RA). Therefore, this study was conducted to investigate how CTGF is associated with the disease progression of RA.Methods
Serum samples were collected from RA patients in active or inactive disease stages, and before or after treatments with infliximab. CTGF production was evaluated by ELISA, RT-PCR, indirect immunofluorescence microscopy, and immunoblotting. Osteoclastogenesis was evaluated using tartrate-resistant acid phosphatase (TRAP) staining, a bone resorption assay and osteoclasts specific catalytic enzymes productions.Results
The serum concentrations of CTGF in RA were greater than in normal healthy controls and disease controls. Interestingly, those were significantly higher in active RA patients compared to inactive RA patients. Furthermore, the CTGF levels significantly were decreased by infliximab concomitant with the disease amelioration. In addition, tumour necrosis factor (TNF)α can induce the CTGF production from synovial fibroblasts even though TNFα can oppositely inhibit the production of CTGF from chondrocytes. CTGF promoted the induction of the quantitative and qualitative activities of osteoclasts in combination with M-CSF and receptor activator of NF-κB ligand (RANKL). In addition, we newly found integrin αVβ3 on the osteoclasts as a CTGF receptor.Conclusions
These results indicate that aberrant CTGF production induced by TNFα plays a central role for the abnormal osteoclastic activation in RA patients. Restoration of aberrant CTGF production may contribute to the inhibition of articular destruction in infliximab treatment. 相似文献60.