Hsp27 overexpression inhibits doxorubicin–induced apoptosis in human breast cancer cells

Previously we demonstrated that heat shock protein 27 (hsp27) overexpression confers resistance to the chemotherapeutic agent doxorubicin in MDA–MB–231 breast cancer cells. Since induction of apoptosis is one underlying mechanism of chemotherapeutic drug action, we investigated the effect of hsp27 overexpression on doxorubicin–induced apoptosis, finding that hsp27 protects MDA–MB–231 cells from apoptosis. We also examined expression of the doxorubicin target, topoisomerase II (topo II), in control and hsp27–overexpressing stable transfectants, as topo II expression is important for both drug sensitivity and the initiation of apoptosis by doxorubicin. The relative levels of both topo II and were higher in the controls than the hsp27–overexpressing clones, suggesting that the apoptotic protective effect of hsp27 overexpression in MDA–MB–231 cells is associated with altered topo II expression.abstract     

Are cognitively impaired individuals adequately represented in community surveys? Recruitment challenges and strategies to facilitate participation in community surveys of older adults. A review

Background: Dementia is the most important age-related disorder and subject to a substantial body of epidemiological research. However, field work in elderly populations faces special challenges which may reduce response rates and invalidate survey results. Therefore, this paper will review more recent prevalence studies of dementia to examine how recruitment issues and their influence on the study outcome have been addressed. Methods: Field studies of the elderly with the main focus on prevalence of dementia published over the last 10 years will be systematically reviewed. The review concerns sampling frames, ways to include institutionalised individuals, response rates and strategies to deal with special challenges of field work in elderly populations such as mortality, fragility and sensory impairment. Furthermore, papers were evaluated regarding the extent to which recruitment outcomes were discussed. Results: The literature is characterised by a disregard of recruitment issues to a varying extent. Mortality, functional dependency and sensory impairment (all positively related to dementia) are barely taken into account in the study design and rarely discussed. As a consequence, cognitively impaired individuals are likely to be underrepresented in most community studies. Conclusion: Strategies to deal with special challenges of field work in the elderly in a systematic manner and to facilitate participation in population surveys of the elderly are crucial and will be outlined. Communication on recruitment issues is essential to improve the validity of study outcomes.     

Heat shock proteins and drug resistance

Summary Heat shock proteins (hsp's) are induced in cells when exposed to different environmental stressful conditions. We have found that breast cancer cells sometimes express high levels of several hsp's, which may both augment the aggressiveness of these tumors and make them more resistant to treatment. We have shown that hsp70 is an ominous prognostic sign as detected by Western blot assays in node-negative breast tumors, and that hsp27 increases specific resistance to doxorubicin in breast cancer cell lines. These findings have direct clinical application, and suggest that modulating hsp expression may be a therapeutic target for reversal of hsp-associated detrimental cellular effects.     

Distribution of Epidermal Growth Factor Receptor Protein Correlates with Gain in Chromosome 7 Revealed by Comparative Genomic Hybridization after Microdissection in Glioblastoma Multiforme

In a recent study, 23 microdissected areas of 10 glioblastoma multiforme (GBM) were investigated for quantitative genomic aberrations using comparative genomic hybridization (CGH). To validate the chromosomal aberrations, as revealed by CGH after microdissection, parallel tissue sections were stained immunohistochemically with an antibody that detects both wild-type epidermal growth factor receptor (EGFR) and the deletion mutant form of the receptor (EGFRvIII). Immunostaining was correlated with CGH data of chromosome 7, because chromosome 7 is the most frequently aberrant chromosome in GBM (here four of 10 tumors), and this aberration often indicates an abnormality of EGFR. Nine of nine areas that showed gain in or amplification (2 areas) of chromosome 7 with CGH contained EGFR-immunoreactive cells. Only three of 14 areas without abnormality of chromosome 7 in CGH contained EGFR-immunoreactive cells; eleven of 14 areas were immunonegative. Our findings demonstrate a strong correlation between immunohistochemistry of EGFR and the copy numbers of chromosome 7, as revealed by CGH after microdissection in glioblastoma multiforme.     

Early reduction of total N-acetyl-aspartate-compounds in patients with classical vanishing white matter disease. A long-term follow-up MRS study

The neuropathology of vanishing white matter (VWM) disease is characterized by a loss of white matter (WM). Although recent histopathological studies suggest a primary glial dysfunction, the purpose of this work was to assess the extent of axonal involvement in VWM using long-term follow-up proton MR spectroscopy. White and gray matter of nine children with genetically proven VWM and late infancy/early childhood onset were investigated with short-echo time, single-voxel proton MR spectroscopy over up to 8 years starting as early as less than 2 years after the onset of symptoms (5 patients). Total N-acetyl-aspartate (-51% from normal control), creatine and phosphocreatine (-47%), and myo-inositol (-49%) were reduced in WM at early disease stages. Choline-containing compounds were less severely decreased (-31%). Follow-up investigations revealed progressive reduction of all metabolites in WM. In gray matter, no distinct changes were detected at early stages. Later total N-acetyl-aspartate decreased slightly (-22%). Assuming the metabolite alterations to primarily reflect changes in cellular composition, the observed pattern indicates early axonal involvement or loss as well as relatively enhanced turnover of myelin. These early stages are followed by a complete cellular loss in cerebral WM.