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排序方式: 共有614条查询结果,搜索用时 437 毫秒
41.
Pauline Wimberger Peter Hillemanns Thomas Kapsner Hermann Hepp Rainer Kimmig 《Analytical cellular pathology》2002,24(4-5):147-158
In gynecologic oncology valid prognostic factors are necessary to define biologically similar subgroups for analysis of therapeutic efficacy. This study is the first published prospective study concerning prognostic significance of DNA ploidy and S-phase fraction in cervical and endometrial cancer following enrichment of tumor cells by cytokeratin labelling. Epithelial cells were labeled by FITC-conjugated cytokeratin antibody (CK 5, 6, 8, and CK 17) prior to flow cytometric cell cycle analysis in 91 specimens of cervical cancer and 73 samples of endometrial cancer. In cervical cancer neither DNA-ploidy nor S-phase fraction were relevant prognostic parameters. But CV of the G(0)G(1)-peak showed prognostic relevance in cervical cancer cells, even in multivariate analysis. This interesting observation, however, seems to have no therapeutic consequence due to the small discrimination capacity of CV. In endometrial carcinoma, gross DNA-aneuploidy (DNA-index > 1.3) and a high percentage of proliferating cells (>75th percentile) were univariate and multivariate highly significant prognostic factors for recurrence-free survival. Especially DNA-aneuploidy (DI>1.3) is one of the most important independent molecular biological prognostic factors. While diagnostic curettage we could identify risk patients even preoperatively by determination of the prognostic factors like histologic tumor type, grading, cervical involvement and DNA-ploidy. Thereby these patients could be treated primarily in an oncologic center. In conclusion, our investigations showed that the determination of DNA-ploidy should be done in endometrial carcinoma. In cervical cancer no clinical significance for determination of DNA-parameters was found. 相似文献
42.
43.
Müller V Viemann D Schmidt M Endres N Ludwig S Leverkus M Roth J Goebeler M 《Journal of immunology (Baltimore, Md. : 1950)》2007,179(12):8435-8445
44.
Bourges D Zhan Y Brady JL Braley H Caminschi I Prato S Villadangos JA Lew AM 《Journal of immunology (Baltimore, Md. : 1950)》2007,179(9):5678-5685
Systemic delivery of Ag usually induces poor mucosal immunity. To improve the CD8 T cell response at mucosal sites, we targeted the Ag to MAdCAM-1, a mucosal addressin cell adhesion molecule expressed mainly by high endothelial venules (HEV) in mesenteric lymph nodes (MLN) and Peyer's patches of gut-associated lymphoid tissue. When chemical conjugates of anti-MAdCAM-1 Ab and model Ag OVA were injected i.v., a greatly enhanced proliferative response of Ag-specific OT-I CD8 T cells was detected in MLN. This was preceded by prolonged accumulation, up to 2 wk, of the anti-MAdCAM OVA conjugate on HEV of Peyer's patches and MLN. In contrast, nontargeted OVA conjugate was very inefficient in inducing OT-I CD8 T cell proliferation in MLN and required at least 20-fold more Ag to induce a comparable response. In addition, MAdCAM targeting elicits an endogenous OVA-specific CD8 T cell response, evident by IFN-gamma production and target killing. Induced response offers protection against an OVA-expressing B cell lymphoma. We propose that the augmentation of gut CD8 T cell responses by MAdCAM targeting is due to both accumulation of Ag in the HEV and conversion of a soluble Ag to a cell-associated one, allowing cross-presentation by DCs. 相似文献
45.
Phylogeography and conservation genetics of a giant lobelia (Lobelia giberroa) in Ethiopian and Tropical East African mountains 总被引:1,自引:0,他引:1
Lobelia giberroa is a giant rosette plant growing in the afro-montane belt of the afro-alpine environment, a unique and little-studied ecosystem occupying the high mountains of eastern Africa. We analysed amplified fragment length polymorphisms (AFLPs) from 11 mountain systems in Ethiopia and Tropical East Africa to infer the phylogeographical history of the species. A total of 191 individuals were investigated from 25 populations. Principal coordinate analysis and population structure analyses revealed three major phylogeographical groups: the Ethiopian mountains and one group on each side of the Rift Valley in Tropical East Africa, respectively: Elgon-Cherangani and Kenya-Aberdare-Kilimanjaro-Meru. Analysis of Molecular Variance showed 55.7% variance among the three groups, suggesting an old divergence. Together with a clear geographical substructure within the main groups, this pattern indicates gradual expansion and supports the montane forest bridge hypothesis, stating that the area occupied by forest was larger and more continuous in previous interglacials and earlier in the present interglacial. Genetic diversity was lower in Ethiopia than in the other two main groups, possibly due to an ancient founder effect when Ethiopia was colonized from the south. 相似文献
46.
Sergey G. Ermilov Dorothee Sandmann Bernhard Klarner Rahaju Widyastuti Stefan Scheu 《ZooKeys》2015,(539):11-51
Seven new species of oribatid mites of the genus Galumna are described from litter and soil materials of Sumatra, Indonesia. A new subgenus, Galumna (Atypicogalumna)
subgen. n., is proposed; it differs from all galumnid genera and subgenera by the simultaneous presence of porose areas and sacculi on the notogaster (vs. either porose areas or sacculi present). Galumna (Galumna) calva Starý, 1997 is recorded for the first time in the Oriental region, and Galumna (Galumna) sabahna Mahunka, 1995 is recorded for the first time in the Indonesian fauna. 相似文献
47.
Deckbar D Jeggo PA Löbrich M 《Critical reviews in biochemistry and molecular biology》2011,46(4):271-283
The DNA damage response pathways involve processes of double-strand break (DSB) repair and cell cycle checkpoint control to prevent or limit entry into S phase or mitosis in the presence of unrepaired damage. Checkpoints can function to permanently remove damaged cells from the actively proliferating population but can also halt the cell cycle temporarily to provide time for the repair of DSBs. Although efficient in their ability to limit genomic instability, checkpoints are not foolproof but carry inherent limitations. Recent work has demonstrated that the G1/S checkpoint is slowly activated and allows cells to enter S phase in the presence of unrepaired DSBs for about 4-6?h post irradiation. During this time, only a slowing but not abolition of S-phase entry is observed. The G2/M checkpoint, in contrast, is quickly activated but only responds to a level of 10-20 DSBs such that cells with a low number of DSBs do not initiate the checkpoint or terminate arrest before repair is complete. Here, we discuss the limitations of these checkpoints in the context of the current knowledge of the factors involved. We suggest that the time needed to fully activate G1/S arrest reflects the existence of a restriction point in G1-phase progression. This point has previously been defined as the point when mitogen starvation fails to prevent cells from entering S phase. However, cells that passed the restriction point can respond to DSBs, albeit with reduced efficiency. 相似文献
48.
Dorothee Aydin Mikhail A Filippov Jakob-Andreas Tschäpe Norbert Gretz Marco Prinz Roland Eils Benedikt Brors Ulrike C Müller 《BMC genomics》2011,12(1):1-17
Background
SOX2 is a key gene implicated in maintaining the stemness of embryonic and adult stem cells. SOX2 appears to re-activate in several human cancers including glioblastoma multiforme (GBM), however, the detailed response program of SOX2 in GBM has not yet been defined.Results
We show that knockdown of the SOX2 gene in LN229 GBM cells reduces cell proliferation and colony formation. We then comprehensively characterize the SOX2 response program by an integrated analysis using several advanced genomic technologies including ChIP-seq, microarray profiling, and microRNA sequencing. Using ChIP-seq technology, we identified 4883 SOX2 binding regions in the GBM cancer genome. SOX2 binding regions contain the consensus sequence wwTGnwTw that occurred 3931 instances in 2312 SOX2 binding regions. Microarray analysis identified 489 genes whose expression altered in response to SOX2 knockdown. Interesting findings include that SOX2 regulates the expression of SOX family proteins SOX1 and SOX18, and that SOX2 down regulates BEX1 (brain expressed X-linked 1) and BEX2 (brain expressed X-linked 2), two genes with tumor suppressor activity in GBM. Using next generation sequencing, we identified 105 precursor microRNAs (corresponding to 95 mature miRNAs) regulated by SOX2, including down regulation of miR-143, -145, -253-5p and miR-452. We also show that miR-145 and SOX2 form a double negative feedback loop in GBM cells, potentially creating a bistable system in GBM cells.Conclusions
We present an integrated dataset of ChIP-seq, expression microarrays and microRNA sequencing representing the SOX2 response program in LN229 GBM cells. The insights gained from our integrated analysis further our understanding of the potential actions of SOX2 in carcinogenesis and serves as a useful resource for the research community. 相似文献49.
Schonn I Hennesen J Dartsch DC 《Apoptosis : an international journal on programmed cell death》2011,16(4):359-369
For DNA targeting anticancer drugs, cellular DNA repair mechanisms may cause resistance and hamper the therapeutic outcome.
DNA damage induced by topoisomerase IIα inhibitors like etoposide and anthracyclines, which are a mainstay of cancer therapy,
is also repaired in many cell types, but the impact and precise mechanisms of this repair are still obscure. To investigate
the DNA damage response of human adenocarcinoma HT29-cells to doxorubicin and to compare the involvement of Ku70 and Rad51
in the repair of doxorubicin- versus etoposide-induced DNA damage, we assessed cell cycle distribution and cell death, DNA
damage, proteins relevant for repair by homologous recombination and non-homologous end-joining, and clonogenicity following
exposure to doxorubicin at clinically achievable concentrations. Also, we assessed changes in the repair kinetics after siRNA-mediated
attenuation of Ku70 or Rad51 expression. We found that exposure to doxorubicin for 24 h induced a substantial amount of DNA
damage that was largely repaired when doxorubicin was removed and the cells were maintained in drug-free medium. Nevertheless,
a pronounced G2/M arrest occurred at times when repair was maximal. This was followed by a distinct increase in cell death and loss of clonogenicity.
In this regard, responses to doxorubicin and etoposide were similar. However, distinct differences in the repair process following
doxorubicin versus etoposide were seen in concentration dependency, time-course and requirement of Ku70 and Rad51 proteins.
In spite of the shared molecular target of doxorubicin and etoposide, DNA lesions induced by these compounds are repaired
differently. 相似文献
50.
Vlkova M Rohousova I Drahota J Stanneck D Kruedewagen EM Mencke N Otranto D Volf P 《PLoS neglected tropical diseases》2011,5(10):e1344