53 research outputs found
Expression of Transketolase like gene 1 (TKTL1) predicts disease-free survival in patients with locally advanced rectal cancer receiving neoadjuvant chemoradiotherapy
<p>Abstract</p> <p>Background</p> <p>For patients with locally advanced rectal cancer (LARC) neoadjuvant chemoradiotherapy is recommended as standard therapy. So far, no predictive or prognostic molecular factors for patients undergoing multimodal treatment are established. Increased angiogenesis and altered tumour metabolism as adaption to hypoxic conditions in cancers play an important role in tumour progression and metastasis. Enhanced expression of Vascular-endothelial-growth-factor-receptor <it>(VEGF-R</it>) and Transketolase-like-1 (<it>TKTL1</it>) are related to hypoxic conditions in tumours. In search for potential prognostic molecular markers we investigated the expression of <it>VEGFR-1</it>, <it>VEGFR-2 </it>and <it>TKTL1 </it>in patients with LARC treated with neoadjuvant chemoradiotherapy and cetuximab.</p> <p>Methods</p> <p>Tumour and corresponding normal tissue from pre-therapeutic biopsies of 33 patients (m: 23, f: 10; median age: 61 years) with LARC treated in phase-I and II trials with neoadjuvant chemoradiotherapy (cetuximab, irinotecan, capecitabine in combination with radiotherapy) were analysed by quantitative PCR.</p> <p>Results</p> <p>Significantly higher expression of <it>VEGFR-1/2 </it>was found in tumour tissue in pre-treatment biopsies as well as in resected specimen after neoadjuvant chemoradiotherapy compared to corresponding normal tissue. High <it>TKTL1 </it>expression significantly correlated with disease free survival. None of the markers had influence on early response parameters such as tumour regression grading. There was no correlation of gene expression between the investigated markers.</p> <p>Conclusion</p> <p>High <it>TKTL-1 </it>expression correlates with poor prognosis in terms of 3 year disease-free survival in patients with LARC treated with intensified neoadjuvant chemoradiotherapy and may therefore serve as a molecular prognostic marker which should be further evaluated in randomised clinical trials.</p
The importance of sedimenting organic matter, relative to oxygen and temperature, in structuring lake profundal macroinvertebrate assemblages
We quantified the role of a main food
resource, sedimenting organic matter (SOM), relative
to oxygen (DO) and temperature (TEMP) in structuring
profundal macroinvertebrate assemblages in
boreal lakes. SOM from 26 basins of 11 Finnish lakes
was analysed for quantity (sedimentation rates),
quality (C:N:P stoichiometry) and origin (carbon
stable isotopes, d13C). Hypolimnetic oxygen and
temperature were measured from each site during
summer stratification. Partial canonical correspondence
analysis (CCA) and partial regression analyses
were used to quantify contributions of SOM, DO and
TEMP to community composition and three macroinvertebrate
metrics. The results suggested a major
contribution of SOM in regulating the community
composition and total biomass. Oxygen best explained
the Shannon diversity, whereas TEMP had largest
contribution to the variation of Benthic Quality Index.
Community composition was most strongly related to d13C of SOM. Based on additional d13C and stoichiometric
analyses of chironomid taxa, marked differences
were apparent in their utilization of SOM and
body stoichiometry; taxa characteristic of oligotrophic
conditions exhibited higher C:N ratios and lower C:P
and N:P ratios compared to the species typical of
eutrophic lakes. The results highlight the role of SOM
in regulating benthic communities and the distributions
of individual species, particularly in oligotrophic
systems
Precise Regulation of Gene Expression Dynamics Favors Complex Promoter Architectures
Promoters process signals through recruitment of transcription factors and RNA polymerase, and dynamic changes in promoter activity constitute a major noise source in gene expression. However, it is barely understood how complex promoter architectures determine key features of promoter dynamics. Here, we employ prototypical promoters of yeast ribosomal protein genes as well as simplified versions thereof to analyze the relations among promoter design, complexity, and function. These promoters combine the action of a general regulatory factor with that of specific transcription factors, a common motif of many eukaryotic promoters. By comprehensively analyzing stationary and dynamic promoter properties, this model-based approach enables us to pinpoint the structural characteristics underlying the observed behavior. Functional tradeoffs impose constraints on the promoter architecture of ribosomal protein genes. We find that a stable scaffold in the natural design results in low transcriptional noise and strong co-regulation of target genes in the presence of gene silencing. This configuration also exhibits superior shut-off properties, and it can serve as a tunable switch in living cells. Model validation with independent experimental data suggests that the models are sufficiently realistic. When combined, our results offer a mechanistic explanation for why specific factors are associated with low protein noise in vivo. Many of these findings hold for a broad range of model parameters and likely apply to other eukaryotic promoters of similar structure
Immunological and parasitological parameters after treatment with dexamethasone in murine Schistosoma mansoni
This work aimed to evaluate the effect of diphenyl dimethyl bicarboxylate (DDB) and dexamethasone alone and in combination with praziquantel on various parasitological, immunological and pathological parameters reflecting disease severity and morbidity in murine schistosomiasis. DDB and dexamethasone had no effect on worm burden but altered tissue egg distribution. This indicates that, under the schedule used, neither drug interfered with the development of adult worms or oviposition, but both can modulate liver pathology. Dexamethasone resulted in a greater reduction in granuloma size than did DDB. Dexamethasone-treated mice also showed lower levels of serum gamma interferon (IFN-γ), interleukin-12 (IL-12) and IL-4, together with higher IL-10 levels, than infected untreated control animals. These data suggest that dexamethasone is a convenient and promising coadjuvant agent that results in decreased morbidity in murine schistosomiasis
High-frequency ventilation and conventional mechanical ventilation in newborn babies with respiratory distress syndrome: A prospective, randomized trial
SCOPUS: ar.jinfo:eu-repo/semantics/publishe
Long-Lasting Effects of Bacterial Lipopolysaccharide Promote Progression of Lupus Nephritis in NZB/W Mice
Prevention of hyaline membrane disease in premature lambs by apneic oxygenation and extracorporeal carbon dioxide removal
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