Publications by authors named "Margit Dlaska"

Immortal cells require a mechanism of telomere length control in order to divide infinitely. One mechanism is telomerase, an enzyme that compensates the loss of telomeric DNA. The second mechanism is the alternative lengthening of telomeres (ALT) pathway.

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Background: Patients suffering from advanced gastric cancer still have a poor prognosis and treatment options are limited. In our previous phase II trial (AGMT-Gastric-1), we showed that the combination of oxaliplatin and irinotecan was well tolerated and effective. The same chemotherapy regimen was now tested in combination with cetuximab in a multicenter phase II trial.

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The end of linear chromosomes forms a lasso-like structure called the t-loop. Such t-loops resemble a DNA recombination intermediate, where the single-stranded 3' overhang is arrested in a stretch of duplex DNA. Presumably, such a t-loop can also be deleted via a recombination process.

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Bone marrow-derived endothelial progenitor cells (EPC) play an important role in neovascularisation and tumor growth. However, the clinical relevance of EPCs on blood vessel formation in non-small cell lung cancer (NSCLC) is unclear. EPC numbers in circulation are very low and therefore their detection is technically challenging.

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Background: S100 A2 and hnRNP A2/B1 (heterogeneous ribonucleoprotein A2/B1) with its splicing variant hnRNP B1 are proteins which are involved in cellular proliferation, differentiation and protein synthesis and are up-regulated in non-small cell lung cancer (NSCLC). Since previous studies using paraffin-embedded tissues indicated a high potential of these markers for diagnosis and screening the present analysis intended to validate these data applying cryostat sections.

Methods: 78 tumor-infiltrated lung cancer specimens and 66 adjacent histologically tumor-free tissues were analyzed; 11 autopsy specimens from patients who did not suffer from a malignant disease served as a control group.

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Mesial temporal lobe epilepsy (TLE) is associated with pronounced anatomical and biochemical changes in the hippocampal formation including extensive neurodegeneration, reorganization of mossy fibres and sprouting of interneurons. Although the anatomical features and some of the physiological consequences of hippocampal remodeling have been well documented, the molecular mechanisms underlying the profound and orientated outgrowth of hippocampal neurons in TLE are not yet understood. The reticulon protein Nogo-A has been associated with an inhibitory action on axon growth and plasticity.

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A real-time PCR technique with automated computerized analysis (TaqMan ) was tested to detect K-ras mutations in 66 patients suffering from NSCLC. This technology is characterized by high reproducibility of data and a time-saving analysis procedure. In 11% (7/66) of the tumour specimens and 2% (1/58) of adjacent tumour-free lung specimens a K-ras codon 12 mutation was detected.

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The frequency of increased EGFR-mRNA expression was determined in 57 patients suffering from NSCLC by applying quantitative real-time PCR. The findings were correlated with clinical parameters and the immunohistochemical (IHC) markers EGFR, c-erbB-2, c-erbB-3, Ki-67 and p53 on cryostat sections. Of the patients 46% showed increased EGFR-mRNA, 35% revealed an increased IHC-EGFR expression; 16% of the patients showed a combined positivity and 35% a combined negativity when applying both methods, and 17 (30%) of the cases revealed increased EGFR-mRNA without IHC-EGFR expression.

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Natural-resistance associated macrophage protein 1 (Nramp1) encodes a transmembrane phagolysosomal protein exerting resistance toward infections with intracellular pathogens by a mechanism not fully elucidated so far. We used the murine macrophage cell line RAW264.7, stably transfected with functional (RAW-37) or nonfunctional (RAW-21) Nramp1, to study for differences in the expression of NO, a central antimicrobial effector molecule of macrophages.

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Objective: Expression of the catalytic subunit of the telomerase enzyme hTERT is essential for prolonging the replicative lifespan and is the rate-limiting step in cellular immortalization and carcinogenesis. Because hTERT expression is positively correlated with telomerase activity, its regulation is suggested as the major determinant of enzymatic activity. The hTERT promoter region contains two CpG islands, which are known to be target sites for de novo DNA methylation.

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