BACKGROUND: Experimental studies for the treatment of relapsed neuroblastoma include the use of hyperthermia in combination with chemotherapeutic drugs. Cytotoxic effects of alkylants and platinum compounds on tumor cells can be enhanced by hyperthermia in various in vitro models. However, the underlying molecular mechanisms are still largely unknown. METHOD: In this study, we used microarray-analysis as a new biological approach to gain insight into the pharmacogenomics and possible target genes of thermochemotherapy. As a model, LAN 1 neuroblastoma cells were treated for 1 h with low doses of cisplatin alone, with simultaneous heating to 42 degrees C or with hyperthermia alone. Gene expression was analyzed at five time points 0 to 24 h after treatment using U95Av2 oligonucleotide arrays (Affymetrix Inc). Significant changes of gene expression levels were calculated by similarity metrices and Pearson correlation. RESULTS: Only a few genes (n = 23) demonstrated altered expression following treatment of LAN 1 cells with cisplatin alone. Hyperthermia alone resulted in significant expression changes of 136 genes in comparison to untreated control cells. Combination therapy of cisplatin and hyperthermia resulted in expression changes of 251 genes, interestingly including 131 genes with unchanged expression under treatment with either cisplatin or hyperthermia alone. Significant changes of expression levels could be annotated to genes involved in heat shock response, protein degradation and apoptosis. These results are now being validated on mRNA- and protein levels by RT-PCR and Western Blot analysis. CONCLUSION: Microarray-Analysis is a suitable new approach for the identification of target genes, which might play an important role for the synergistic effect of hyperthermia and chemotherapy in tumor cells.

Antineoplastic Agents↗

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Proteomics: techniques and applications in cancer research.

Proteomics can be defined as functional analysis of the full set of proteins by high-throughput technologies in a given system. The workflow of proteomics is a multi-step process comprising sample preparation, separation, quantification and identification of proteins. Due to the high complexity of different protein species and the wide dynamic range of protein amount within a cell system it is necessary to apply appropriate analysis methods. One approach is to separate proteins first by two-dimensional gel electrophoresis (2-DE) according to charge and molecular weight. Proteins are then fragmented and analyzed using matrix-assisted laser desorption ionisation time-of-flight mass spectrometry (MALDI-TOF MS). Identification of proteins can be achieved by comparing the mass/charge-ratios of these peptides to respective databases. Proteome analysis with respect to the identification of disease-associated patterns of molecules in different tissues is in the early stages, because standardisation of these techniques often remains to be established. However, proteome analyses is a promising tool to obtain holistic insights into the physiological status of a cell or cellular system. Compared to RNA-based studies some advantages are obvious: (1) post-translational modifications, e. g. phosphorylation, contributing to the activity status can be detected at the protein level only, (2) RNA-levels do not necessarily coincide with protein levels for a particular gene, (3) feedback-mechanisms within regulatory pathways can control protein activity without measurable changes in mRNA content.

Algorithms↗

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[Risk factors in stroke with special reference to aging].

Because of the deleterious consequences of strokes the detection and therapy of risk factors are particularly important. After a short description of the different subtypes of stroke and their age distribution the possible risk factors are discussed. The leading factor is arterial hypertension, followed by diabetes mellitus, but smoking, hyperlipemia and obesity are not held to be definite risk factors. In spite of the positive correlation between age and stroke incidence, aging is probably not a risk factor by itself, but it is accompanied by higher frequencies of other risk factors.

Aged↗

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[The nursing school library].

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Libraries, Nursing↗

PubMedDate not supplied

[Report on a gerontological lecture tour in the Peoples Republic of China].

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Aged↗

PubMedDate not supplied

[Changes in kidney function and morphology in the aged].

Increasing age of man leads to macroscopical and microscopical alterations in the kidneys. They cause a reduction of renal plasma flow, glomerular filtration rate and other renal functions. The characteristics of creatinine, blood urea nitrogen and uric acid in old people up to hundred years and over are discussed with regard to vitality and sex. The result of the reduction of kidney function is only a fully compensated renal insufficiency without need of specific therapy, but with need of dose reduction of drugs excreted with urine. The radiological renal cortical index (Vuorinen) is higher in old age because of the involution of renal cortical parenchyma. The sonographic B-scan is able to show these findings as well and to delimit them from pathological ones.

Adult↗