Search results for "Chromosomal instability"
showing 5 items of 15 documents
High resistance to X-rays and therapeutic carbon ions in glioblastoma cells bearing dysfunctional ATM associates with intrinsic chromosomal instabili…
2014
To investigate chromosomal instability and radiation response mechanisms in glioblastoma cells.We undertook a comparative analysis of two patient-derived glioblastoma cell lines. Their resistance to low and high linear energy transfer (LET) radiation was assessed using clonogenic survival assay and their intrinsic chromosome instability status using fluorescence in situ hybridization. DNA damage was analyzed by pulsed-field gel electrophoresis and by γ-H2AX foci quantification. Expression of DNA damage response proteins was assessed by immunoblot.Increased radioresistance to X-rays as well as carbon ions was observed in glioblastoma cells exhibiting high levels of naturally occurring chromo…
Patterns of genomic instability in gastric cancer: clinical implications and perspectives
2007
In gastric cancer (GC) the loss of genomic stability represents a key molecular step that occurs early in the carcinogenesis process and creates a permissive environment for the accumulation of genetic and epigenetic alterations in tumor suppressor genes and oncogenes. It is widely accepted that GC can follow at least two major genomic instability pathways, microsatellite instability (MSI) and chromosome instability (CIN). MSI is responsible for a well-defined subset of GCs. CIN represents a more common pathway comprising heterogeneous subsets of GC. In addition to MSI and CIN, the CpG islands methylator phenotype (CIMP) plays an important role in gastric carcinogenesis. CIMP may lead to th…
RNAi mediated acute depletion of Retinoblastoma protein (pRb) promotes aneuploidy in human primary cells via micronuclei formation
2009
BACKGROUND: Changes in chromosome number or structure as well as supernumerary centrosomes and multipolar mitoses are commonly observed in human tumors. Thus, centrosome amplification and mitotic checkpoint dysfunctions are believed possible causes of chromosomal instability. The Retinoblastoma tumor suppressor (RB) participates in the regulation of synchrony between DNA synthesis and centrosome duplication and it is involved in transcription regulation of some mitotic genes. Primary human fibroblasts were transfected transiently with short interfering RNA (siRNA) specific for human pRb to investigate the effects of pRb acute loss on chromosomal stability. RESULTS: Acutely pRb-depleted fibr…
Telomere shortening and chromosomal instability abrogates proliferation of adult but not embryonic neural stem cells.
2004
Chromosome integrity is essential for cell viability and, therefore, highly proliferative cell types require active telomere elongation mechanisms to grow indefinitely. Consistently, deletion of telomerase activity in a genetically modified mouse strain results in growth impairments in all highly proliferative cell populations analyzed so far. We show that telomere attrition dramatically impairs the in vitro proliferation of adult neural stem cells (NSCs) isolated from the subventricular zone (SVZ) of telomerase-deficient adult mice. Reduced proliferation of postnatal neurogenic progenitors was also observed in vivo, in the absence of exogenous mitogenic stimulation. Strikingly, severe telo…
Does the evidence matter in medicine? The retinoblastoma paradigm.
2007
Retinoblastoma (Rb) is the most common intraocular malignant tumour in childhood, with an incidence of 1 in 15,000 live births. Complete information on this rare tumour can be easily accessed through the internet, although many aspect concerning the aetiology and pathogenesis of the disease, are still controversial. The "two hit" theory, formulated in 1971 to explain the variegated clinical expression of the disease, is based on the idea that single gene mutation may determine the development of cancer. However, this view does not take into account the most recent evidences showing the role of aneuploidy and chromosome instability in cancer. Also, a number of other genes and epigenetic mech…