SwePub
Sök i SwePub databas

  Utökad sökning

Träfflista för sökning "L773:0143 3334 srt2:(2005-2009)"

Sökning: L773:0143 3334 > (2005-2009)

  • Resultat 1-10 av 34
  • [1]234Nästa
Sortera/gruppera träfflistan
   
NumreringReferensOmslagsbildHitta
1.
  • Bivik, Cecilia, et al. (författare)
  • Hsp70 protects against UVB induced apoptosis by preventing release of cathepsins and cytochrome c in human melanocytes
  • 2007
  • Ingår i: Carcinogenesis. - 0143-3334 .- 1460-2180. ; 28:3, s. 537-544
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>Stress-induced heat shock protein 70 (Hsp70) effectively protects<sup> </sup>cells against apoptosis, although the anti-apoptotic mechanism<sup> </sup>is still undefined. Exposure of human melanocytes to heat and<sup> </sup>subsequent UVB irradiation increased the level of Hsp70 and<sup> </sup>pre-heating reduced UVB induced apoptosis. Immunofluorescence<sup> </sup>staining of Hsp70 in combination with staining of lysosomes<sup> </sup>(Lamp2) or mitochondria (Mitotracker<sup>®</sup>) in pre-heated UVB<sup> </sup>exposed cells showed co-localization of Hsp70 with both lysosomes<sup> </sup>and mitochondria in the surviving cell population. Furthermore,<sup> </sup>UVB induced apoptosis was accompanied by lysosomal and mitochondrial<sup> </sup>membrane permeabilization, detected as release of cathepsin<sup> </sup>D and cytochrome <em>c</em>, respectively, which were prevented by heat<sup> </sup>pre-treatment. In purified fractions of lysosomes and mitochondria,<sup> </sup>recombinant Hsp70 attached to both lysosomal and mitochondrial<sup> </sup>membranes. Moreover, in apoptotic cells Bax was translocated<sup> </sup>from a diffuse cytosolic location into punctate mitochondrial-like<sup> </sup>structures, which was inhibited by Hsp70 induction. Such inhibition<sup> </sup>of Bax translocation was abolished by transfection with Hsp70<sup> </sup>siRNA. Furthermore, Hsp70 siRNA eliminated the apoptosis preventive<sup> </sup>effect observed after pre-heating. These findings show Hsp70<sup> </sup>to rescue melanocytes from UVB induced apoptosis by preventing<sup> </sup>release of cathepsins from lysosomes, Bax translocation and<sup> </sup>cytochrome <em>c</em> release from mitochondria.<sup> </sup></p> <p> </p> <p><strong>Abbreviations:</strong> AIF, apoptosis-inducing factor; Hsp, heat shock protein; NAG, ß-<em>N</em>-acetylglucosaminidase; tBid, truncated Bid; UV, ultraviolet</p>
  •  
2.
  •  
3.
  • Bonassi, Stefano, et al. (författare)
  • An increased micronucleus frequency in peripheral blood lymphocytes predicts the risk of cancer in humans
  • 2007
  • Ingår i: Carcinogenesis. - Oxford University Press. - 0143-3334. ; 28:3, s. 625-631
  • Tidskriftsartikel (refereegranskat)abstract
    • The frequency of micronuclei (MN) in peripheral blood lymphocytes (PBL) is extensively used as a biomarker of chromosomal damage and genome stability in human populations. Much theoretical evidence has been accumulated supporting the causal role of MN induction in cancer development, although prospective cohort studies are needed to validate MN as a cancer risk biomarker. A total of 6718 subjects from of 10 countries, screened in 20 laboratories for MN frequency between 1980 and 2002 in ad hoc studies or routine cytogenetic surveillance, were selected from the database of the HUman MicroNucleus (HUMN) international collaborative project and followed up for cancer incidence or mortality. To standardize for the inter-laboratory variability subjects were classified according to the percentiles of MN distribution within each laboratory as low, medium or high frequency. A significant increase of all cancers incidence was found for subjects in the groups with medium (RR = 1.84; 95% CI: 1.28-2.66) and high MN frequency (RR = 1.53; 1.04-2.25). The same groups also showed a decreased cancer-free survival, i.e. P = 0.001 and P = 0.025, respectively. This association was present in all national cohorts and for all major cancer sites, especially urogenital (RR = 2.80; 1.17-6.73) and gastro-intestinal cancers (RR = 1.74; 1.01-4.71). The results from the present study provide preliminary evidence that MN frequency in PBL is a predictive biomarker of cancer risk within a population of healthy subjects. The current wide-spread use of the MN assay provides a valuable opportunity to apply this assay in the planning and validation of cancer surveillance and prevention programs.
4.
  • Bonassi, Stefano, et al. (författare)
  • Chromosomal aberration frequency in lymphocytes predicts the risk of cancer: results from a pooled cohort study of 22 358 subjects in 11 countries
  • 2008
  • Ingår i: Carcinogenesis. - Oxford University Press. - 0143-3334. ; 29:6, s. 1178-1183
  • Tidskriftsartikel (refereegranskat)abstract
    • Mechanistic evidence linking chromosomal aberration (CA) to early stages of cancer has been recently supported by the results of epidemiological studies that associated CA frequency in peripheral lymphocytes of healthy individuals to future cancer incidence. To overcome the limitations of single studies and to evaluate the strength of this association, a pooled analysis was carried out. The pooled database included 11 national cohorts and a total of 22 358 cancer-free individuals who underwent genetic screening with CA for biomonitoring purposes during 1965-2002 and were followed up for cancer incidence and/or mortality for an average of 10.1 years; 368 cancer deaths and 675 incident cancer cases were observed. Subjects were classified within each laboratory according to tertiles of CA frequency. The relative risk (RR) of cancer was increased for subjects in the medium [RR = 1.31, 95% confidence interval (CI) = 1.07-1.60] and in the high (RR = 1.41; 95% CI = 1.16-1.72) tertiles when compared with the low tertile. This increase was mostly driven by chromosome-type aberrations. The presence of ring chromosomes increased the RR to 2.22 (95% CI = 1.34-3.68). The strongest association was found for stomach cancer [RRmedium = 1.17 (95% CI = 0.37-3.70), RRhigh = 3.13 (95% CI = 1.17-8.39)]. Exposure to carcinogens did not modify the effect of CA levels on overall cancer risk. These results reinforce the evidence of a link between CA frequency and cancer risk and provide novel information on the role of aberration subclass and cancer type.
5.
  • Brendle, Annika, et al. (författare)
  • Polymorphisms in predicted microRNA-binding sites in integrin genes and breast cancer ITGB4 as prognostic marker.
  • 2008
  • Ingår i: Carcinogenesis. - Oxford University Press. - 0143-3334 .- 1460-2180. ; 29:7, s. 1394-1399
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>Integrins control the cell attachment to the extracellular matrix and play an important role in mediating cell proliferation, migration and survival. A number of important cancer-associated integrin genes can be regulated by microRNAs (miRNAs) that bind to their target sites in the 3' untranslated regions. We examined the effect of single-nucleotide polymorphisms (SNPs) in predicted miRNA target sites of six integrin genes (ITGA3, ITGA6, ITGAv, ITGB3, ITGB4 and ITGB5) on breast cancer (BC) risk and clinical outcome. Six SNPs were genotyped in 749 Swedish incident BC cases with detailed clinical data and up to 15 years of follow-up together with 1493 matched controls. We evaluated associations between genotypes and BC risk and clinical tumour characteristics. Survival probabilities were compared between different subgroups. As a novel finding, several SNPs seemed to associate with the hormone receptor status. The strongest association was observed between the A allele of the SNP rs743554 in the ITGB4 gene and oestrogen receptor-negative tumours [odds ratio 2.09, 95% confidence intervals (CIs) 1.19-3.67]. The same SNP was associated with survival. The A allele carriers had a worse survival compared with the wild-type genotype carriers (hazard ratio 2.11, 95% CIs 1.21-3.68). The poor survival was significantly associated with the aggressive tumour characteristics: high grade, lymph node metastasis and high stage. None of the SNPs was significantly associated with BC risk. As the ITGB4 SNP seems to influence tumour aggressiveness and survival, it may have prognostic value in the clinic.</p>
  •  
6.
7.
  • Chien, Ming-Hsien, et al. (författare)
  • Vascular endothelial growth factor-C (VEGF-C) promotes angiogenesis by induction of COX-2 in leukemic cells via the VEGF-R3/JNK/AP-1 pathway.
  • 2009
  • Ingår i: Carcinogenesis. - 0143-3334 .- 1460-2180. ; 30:12, s. 2005-13
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>Vascular endothelial growth factor (VEGF)-C is recognized as a tumor lymphangiogenic factor based on the effects of activated VEGF-R3 on lymphatic endothelial cells. Many tumor cells express VEGF-R3 but the function of this receptor in tumor cells is largely unknown. It has been reported that the VEGF-C/VEGF-R3 axis is activated in subsets of leukemia patients. Herein, we have shown that VEGF-C induces angiogenic activity in the tube formation assay invitro and Matrigel plug assay in vivo by upregulating an angiogenic factor, cyclooxygenase-2 (COX-2), through VEGF-R3 in the human acute myeloid leukemia (AML) cell line, THP-1. COX-2 induction by VEGF-C was also observed in other VEGF-R3(+) human AML cell lines (U937 and HL60). Moreover, immunohistochemical analysis of bone marrow specimens of 37 patients diagnosed with AML revealed that VEGF-C expression in specimens was associated with the expression of COX-2 (P &lt; 0.001). The manner by which signaling pathways transduced by VEGF-C is responsible for COX-2 upregulation was further investigated. Blocking the p42/44 mitogen-activated protein kinase (MAPK) pathway with the MAPK kinase inhibitor, PD 98059, failed to inhibit VEGF-C-mediated COX-2 expression. However, VEGF-C-induced COX-2 upregulation was effectively abolished by overexpression of dominant-negative c-Jun N-terminal kinase (JNK) or treatment with the JNK inhibitor, SP 600125. VEGF-C induced JNK-dependent nuclear translocation of c-Jun. Furthermore, chromatin immunoprecipitation and reporter assays revealed that VEGF-C enhanced c-Jun binding to the cyclic adenosine 3',5'-monophosphate-response element of the COX-2 promoter and induced COX-2 expression. In sum, the data herein highlight the pathogenic role of VEGF-C in leukemia via regulation of angiogenesis through upregulation of COX-2.</p>
  •  
8.
  • Dossus, Laure, et al. (författare)
  • Polymorphisms of genes coding for ghrelin and its receptor in relation to anthropometry, circulating levels of IGF-I and IGFBP-3, and breast cancer risk a case-control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC)
  • 2008
  • Ingår i: Carcinogenesis. - Oxford University Press. - 0143-3334 .- 1460-2180. ; 29:7, s. 1360-1366
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>Ghrelin, an endogenous ligand for the growth hormone secretagogue receptor, has two major functions: the stimulation of the growth hormone production and the stimulation of food intake. Accumulating evidence also suggests a role of ghrelin in cancer development. We conducted a case-control study on 1359 breast cancer cases and 2389 matched controls, nested within the European Prospective Investigation into Cancer and Nutrition, to examine the association of common genetic variants in the genes coding for ghrelin (GHRL) and its receptor (GHSR) with anthropometric measures, circulating insulin growth factor I (IGF-I) and insulin-like growth factor-binding protein 3 and breast cancer risk. Pair-wise tagging was used to select the 15 polymorphisms that represent the majority of common genetic variants across the GHRL and GHSR genes. A significant increase in breast cancer risk was observed in carriers of the GHRL rs171407-G allele (odds ratio: 1.2; 95% confidence interval: 1.0-1.4; P = 0.02). The GHRL single-nucleotide polymorphism rs375577 was associated with a 5% increase in IGF-I levels (P = 0.01). A number of GHRL and GHSR polymorphisms were associated with body mass index (BMI) and height (P between &lt;0.01 and 0.04). The false-positive report probability (FPRP) approach suggests that these results are noteworthy (FPRP &lt; 0.20). The results presented here add to a growing body of evidence that GHRL variations are associated with BMI. Furthermore, we have observed evidence for association of GHRL polymorphisms with circulating IGF-I levels and with breast cancer risk. These associations, however, might also be due to chance findings and further large studies are needed to confirm our results.</p>
  •  
9.
  • Goulet, Anne-Christine, et al. (författare)
  • Selenomethionine induces sustained ERK phosphorylation leading to cell-cycle arrest in human colon cancer cells
  • 2005
  • Ingår i: Carcinogenesis. - 0143-3334 .- 1460-2180. ; 26:1, s. 109-117
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>Selenomethionine (SeMet) is being tested alone and in combination with other agents in cancer chemoprevention trials. However, the molecular targets and the signaling mechanism underlying the anticancer effect of this compound are not completely clear. Here, we provide evidence that SeMet can induce cell-growth arrest and that the growth inhibition is associated with S-G2/M cell-cycle arrest. Coincidentally with the cell-cycle arrest, we observed a striking increase in cyclin B as well as phosphorylation of the cyclin-dependent kinase Cdc2. Since activation of the mitogen-activated protein kinase (MAPK) cascade has been associated with cell-cycle arrest and growth inhibition, we evaluated the activation of extracellular signal-regulated kinase (ERK). We found that SeMet induced phosphorylation of the MAPK ERK in a dose-dependent manner. We also demonstrate phosphorylation of ribosomal S6 kinase (p90RSK) by SeMet. Additionally, we show phosphorylation of histone H3 in a concentration-dependent manner. Furthermore, the phosphorylation of p90RSK and histone H3 were both antagonized by the MEK inhibitor U0126, implying that SeMet-induced phosphorylation of p90RSK and histone H3 are at least in part ERK pathway dependent. Based on these results, we propose that SeMet induced growth arrest and phosphorylation of histone H3 are mediated by persistent ERK and p90RSK activation. These new data provide valuable insights into the biological effects of SeMet at clinically relevant concentrations.</p>
  •  
10.
  • Heikkinen, Katri, et al. (författare)
  • RAD50 and NBS1 are breast cancer susceptibility genes associated with genomic instability
  • 2006
  • Ingår i: Carcinogenesis. - Oxford University Press. - 0143-3334. ; 27:8, s. 1593-1599
  • Tidskriftsartikel (refereegranskat)abstract
    • The Mre11 complex, composed of RAD50, NBS1 and MRE11, has an essential role in the maintenance of genomic integrity and preventing cells from malignancy. Here we report the association of three Mre11 complex mutations with hereditary breast cancer susceptibility, studied by using a case-control design with 317 consecutive, newly diagnosed Northern Finnish breast cancer patients and 1000 geographically matched healthy controls (P = 0.0004). RAD50 687delT displayed significantly elevated frequency in the studied patients (8 out of 317, OR 4.3, 95% CI 1.5-12.5, P = 0.008), which indicates that it is a relatively common low-penetrance risk allele in this cohort. Haplotype analysis and the screening of altogether 512 additional breast cancer cases from Sweden, Norway and Iceland suggest that RAD50 687delT is a Finnish founder mutation, not present in the other Nordic cohorts. The RAD50 IVS3-1G > A splicing mutation leading to translational frameshift was observed in one patient, and the NBS1 Leu150Phe missense mutation affecting a conserved residue in the functionally important BRCA1 carboxyterminal (BRCT) domain in two patients, both being absent from 1000 controls. Microsatellite marker analysis showed that loss of the wild-type allele was not involved in the tumorigenesis in any of the studied mutation carriers, but they all showed increased genomic instability assessed by cytogenetic analysis of peripheral blood T-lymphocytes (P = 0.006). In particular, the total number of chromosomal rearrangements was significantly increased (P = 0.002). These findings suggest an effect for RAD50 and NBS1 haploinsufficiency on genomic integrity and susceptibility to cancer.
Skapa referenser, mejla, bekava och länka
  • Resultat 1-10 av 34
  • [1]234Nästa
 
pil uppåt Stäng

Kopiera och spara länken för att återkomma till aktuell vy