| 1. |
- Rösch, Frank, et al.
(författare)
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Radiolanthanides in nuclear medicine.
- 2004
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Ingår i: Metal ions in biological systems. - 0161-5149. ; 42, s. 77-108
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Forskningsöversikt (refereegranskat)
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| 2. |
- Rahpeymai, Neda, et al.
(författare)
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Microarray-based diagnosis of breast cancer using decision trees
- 2003
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Konferensbidrag (refereegranskat)abstract
- We apply the decision tree algorithm C4.5 to gene expression data in order to induce decision trees for identification of breast cancer patients. Using expression data from 108 known breast cancer-related genes for 75 patients with various diseases of the breast, we are able to induce decision trees with 89% accuracy in separating cancer from non-cancer patients in a cross-validation test. We also show that by inducing a separate decision tree for each cancer-related gene, and using the expression level of the individual gene as the decision variable, it is possible to obtain decision trees which aid the understanding of signaling pathways involved in breast cancer. In addition, we also show that the C4.5 algorithm is able to identify key breast cancer genes when decision trees are induced on expression data sets containing randomly selected genes. This result indicates that it is possible to make biological discoveries when applying decision tree algorithms to large sets of gene expression data in diseases where the genetic basis is not well characterised.
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| 3. |
- Philchenkov, A., et al.
(författare)
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Caspases and cancer : Mechanisms of inactivation and new treatment modalities
- 2004
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Ingår i: Experimental Oncology. - 0204-3564. ; 26:2, s. 82-97
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Tidskriftsartikel (refereegranskat)abstract
- Elimination of superfluous or mutated somatic cells is provided by various mechanisms including apoptosis. Deregulation of apoptotic signaling pathways may contribute to oncogenesis. Aspartate specific cysteine proteases, termed caspases are the key effector molecules in apoptosis. The aim of this review is to summarize the various defects in caspase-dependent cell death machinery identified in the neoplastic cells. These include not only mutations, but also alterations of gene methylation, and altered mRNA stability. Among the molecules that we discuss are elements of the extrinsic death pathway like CD95 (APO-1/Fas), FADD, FLIPs, FLICE, other apical caspases, components of the intrinsic apoptotic pathway like Apaf-1, caspase-9, and modulators of apoptotic pathways like IAPs, Smac/DIABLO, OMI/HtrA2, and other apoptosis regulating proteins. We also discuss recent data on cancer-specific agents that target effector mechanisms of apoptosis. Particular emphasis is given to the prospects for combining cell suicide-activating approaches with classical cancer therapies.
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| 4. |
- Hautaniemi, S, et al.
(författare)
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A strategy for identifying putative causes of gene expression variation in human cancers
- 2004
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Ingår i: Journal of the Franklin Institute. - : Elsevier BV. - 0016-0032. ; 341:1-2, s. 77-88
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Tidskriftsartikel (refereegranskat)abstract
- The majority of microarray studies focus on analysis of gene expression differences between various specimens or conditions. However, the causes of this variability from one cancer to another, from one sample to another and from one gene to another often remain unknown. In this study, we present a systematic procedure for finding genes whose expression levels are altered due to an intrinsic or extrinsic explanatory phenomenon. The procedure consists of three stages: preprocessing, data integration and statistical analysis. We tested and verified the utility of this approach in a case study, where expression and copy number levels of 13,824 genes were determined in 14 breast cancer cell lines. The procedure resulted in identification of 92 genes whose expression levels could be explained by the variability of gene copy number. This set includes several genes that are known to be both overexpressed and amplified in breast cancer. Thus, these genes may represent an important set of primary, genetically altered genes that drive cancer progression. (C) 2003 The Franklin Institute.
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| 5. |
- Ruuth, Kristina, et al.
(författare)
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Interferon-alpha promotes survival of human primary B-lymphocytes via phoshatidylinositol 3-kinase
- 2001
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Ingår i: Biochemical and Biophysical Research Communications - BBRC. - : Academic Press. - 0006-291X .- 1090-2104. ; 284:3, s. 583-586
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Tidskriftsartikel (refereegranskat)abstract
- Signaling pathways for the antiviral and antiproliferative biological effects of type I interferons (IFN) are well established. In this report we demonstrate a novel signaling pathway for IFN-α, as it induced rapid phosphorylation of both PKB/Akt and its substrate forkhead. The PI3-kinase inhibitor LY294002 abolished these phosphorylations. PI3-kinase has been implicated in cell survival mediating its effect through the second messenger PIP3 and the subsequent activation of PKB/Akt. We could show that IFN-α inhibited spontaneous apoptosis of primary B-lymphocytes, in the absence of a mitogenic stimulus. This effect was inhibited by LY294002. Thus, our data suggests that IFN-α promotes survival of peripheral B-lymphocytes via the PI3-kinase-PKB/Akt pathway. In addition, IFN-α stimulation of anti-IgM activated cells resulted in downregulated expression of the cell cycle inhibitor p27/Kip1.
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| 6. |
- Jensen, LK, et al.
(författare)
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Optical coherence tomography in clinical examination of non-pigmented skin malignancies
- 2003
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Ingår i: OPTICAL COHERENCE TOMOGRAPHY AND COHERENCE TECHNIQUES. - : SPIE. - 0277-786X .- 1996-756X. - 0819450103 ; 5140, s. 160-160
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Konferensbidrag (refereegranskat)abstract
- Optical coherence tomography (OCT) images of basal cell carcinomas (BCCs) have been acquired using a compact handheld probe with an integrated video camera allowing the OCT images to be correlated to a skin surface image. In general the healthy tissue of the skin has an obvious stratified structure, whereas the cancerous tissue shows a more homogenous structure. Thus it was demonstrated that it is possible to distinguish BCCs from healthy tissue by means of OCT. Furthermore different histological types of BCC were identified. Comparison of OCT images taken prior to and immediately after photodynamic therapy clearly shows the tissue response to the treatment, and indicates local oedema in the treated area.
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| 7. |
- Ghavami, Saeid, et al.
(författare)
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Mechanism of apoptosis induced by S100A8/A9 in colon cancer cell lines : the role of ROS and the effect of metal ions
- 2004
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Ingår i: Journal of Leukocyte Biology. - : Oxford University Press (OUP). - 0741-5400 .- 1938-3673. ; 76:1, s. 169-175
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Tidskriftsartikel (refereegranskat)abstract
- The protein complex S100A8/A9, abundant in the cytosol of neutrophils, is secreted from the cells upon cellular activation and induces apoptosis in tumor cell lines and normal fibroblasts in a zinc-reversible manner. In the present study, we present evidence that the S100A8/A9 also exerts its apoptotic effect by a zinc-independent mechanism. Treatment of the colon carcinoma cells with different concentrations of human SI00A8/A9 or the metal ion chelator diethylenetriaminepentacetic acid (DTPA) resulted in a significant increase of cell death. Annexin V/phosphatidylinositol and Hoechst 33258 staining revealed that cell death was mainly of the apoptotic type. A significant increase in the activity of caspase-3 and -9 was observed in both cell lines after treatment. Caspase-8 activation was negligible in both cell lines. The cytotoxicity/apoptotic effect of human SI00A8/A9 and DTPA was inhibited significantly 2 2 (P<0.05) by Zn+2 and Cu+2, more effectively than by Ca2+ and Mg2+. The antioxidant N-acetyl-L-cysteine inhibited the cytotoxicity/apoptotic effect of SI00A8/A9 and DTPA. However, as a result of the different time-courses of both agents and that the S100A8/A9-induced apoptosis was not completely reversed, we conclude that S100A8/A9 exerts its apoptotic effect on two colon carcinoma cell lines through a dual mechanism: one via zinc exclusion from the target cells and the other through a yet-undefined mechanism, probably relaying on the cell-surface receptor(s).
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| 8. |
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| 9. |
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| 10. |
- Baust, H., et al.
(författare)
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Evidence for radiosensitizing by gliotoxin in HL-60 cells : implications for a role of NF-kappa B independent mechanisms
- 2003
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Ingår i: Oncogene. - : Springer Science and Business Media LLC. - 0950-9232 .- 1476-5594. ; 22:54, s. 8786-8796
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Tidskriftsartikel (refereegranskat)abstract
- Radioresistance markedly impairs the efficacy of tumor radiotherapy and may involve antiapoptotic signal transduction pathways that prevent radiation-induced cell death. A common cellular response to genotoxic stress induced by radiation is the activation of the nuclear factor kappa B (NF-kappaB). NF-kappaB activation in turn can lead to an inhibition of radiation-induced apoptotic cell death. Thus, inhibition of NF-kappaB activation is commonly regarded as an important strategy to abolish radioresistance. Among other compounds, the fungal metabolite gliotoxin (GT) has been reported to be a highly selective inhibitor of NF-kappaB activation. Indeed, low doses of GT were sufficient to significantly enhance radiation-induced apoptosis in HL-60 cells. However, this effect turned out to be largely independent of NF-kappaB activation since radiation of HL-60 cells with clinically relevant doses of radiation induced only a marginal increase in NF-kappaB activity, and selective inhibition of NF-kappaB by SN50 did not result in a marked enhancement of GT-induced apoptosis. GT induced activation of JNKs, cytochrome c release from the mitochondria and potently stimulated the caspase cascade inducing cleavage of caspases -9, -8, -7 and -3. Furthermore, cleavage of the antiapoptotic protein X-linked IAP and downregulation of the G2/M-specific IAP-family member survivin were observed during GT-induced apoptosis. Finally, the radiation-induced G2/M arrest was markedly reduced in GT-treated cells most likely due to the rapid induction of apoptosis. Our data demonstrate that various other pathways apart from the NF-kappaB signaling complex can sensitize tumor cells to radiation and propose a novel mechanism for radio-sensitization by GT, the interference with the G2/M checkpoint that is important for repair of radiation-induced DNA damage in p53-deficient tumor cells.
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