PubMed · 14862127
The source did not provide an abstract. Follow the original record for more information.
Explore connections, maps & timelines
H CHIARI. 1951-08-01. [Pathologic-anatomical report].. https://pubmed.ncbi.nlm.nih.gov/14862127/
Cite the original work for its findings. Save a collection to share your selection of sources.
KEEP EXPLORING
PURPOSE: The aim of this study was to evaluate whether quantitative changes in contrast enhancement (CE) after neoadjuvant chemotherapy (NC) are associated with histological signs of tumor regression and whether quantitative dynamic MRI (dMRI) is capable of accurately assessing preoperative tumor size compared to mammography (MG) and ultrasound (US). METHODS: Thirty-one patients with breast cancer underwent MRI before and after NC. Dynamic CE was measured using a turbo-FLASH sequence and quantified by a two-compartment model, where two parameters, k(ep) (distribution constant rate) and A (amplitude), were calculated and color mapped. RESULTS: When tumors had signs of histological regression in the operative specimen (n=17) decrease of the parameters A and k(ep) was significantly more marked compared to tumors without regression (n=12). The correlation between tumor size measured by dMRI and histopathology was 0.81 when areas of unspecific CE were included; when they were not included the correlation was 0.66 and tumor size was systematically underestimated. In 26 patients dMRI was retrospectively compared with MG (r=0.51; dMRI, r=0.80) and in 22 patients with US (r=0.60; dMRI, r=0.75). CONCLUSION: Changes in dynamic CE are associated with histological tumor regression. Quantitative dMRI enables a valid assessment of tumor residue and is superior to MG and US. Remaining unspecific CE within the original tumor site should be considered as potentially malignant.
Increasing evidence suggests that tissue inhibitor of metalloproteinases-1 (TIMP-1) can directly regulate cell growth and apoptosis independent of its matrix metalloproteinases (MMPs)-inhibitory activity. While TIMP-1's antiapoptotic activity has been well demonstrated, conflicting data has been reported regarding TIMP-1's role in growth regulation. Here we show that TIMP-1 reduces the growth rate of human breast epithelial (MCF10A) cells by inducing cell cycle arrest at G(1). TIMP-1-mediated cell cycle arrest is associated with its downregulation of cyclin D(1) and upregulation of p27(KIP1), resulting in inhibition of cyclin-dependent kinase activity necessary for phosphorylation of the tumor suppressor retinoblastoma protein. We further show that TIMP-1 modulation of cyclin D(1) and p27(KIP1) is achieved through TIMP-1-mediated differential regulation of protein stability independent of growth factor signaling. We also show that TIMP-1-mediated differential regulation of cyclin D(1) and p27(KIP1) is independent of cell adhesion signaling. Whereas approximately 50% of MCF10A cells with reduced TIMP-1 expression underwent cell death following loss of cell adhesion (anoikis), TIMP-1 overexpressing cells remained viable with prominent cell cycle arrest without detectable cell death. Taken together, we propose that TIMP-1-mediated cell survival independent of cell adhesion is accompanied with cell cycle arrest in human breast epithelial cells, although cell cycle regulation may not be a prerequisite for TIMP-1 regulation of apoptosis in general.
Genetic analysis indicates that TP63 is required for establishment and preservation of self-renewing progenitors within the basal layer of several epithelial structures, however, the specific contributions of transactivating (TA-p63) and dominant-negative (DeltaN-p63) isoforms remain largely undefined. Recent studies have suggested a model in which TA-p63 plays an important role in the establishment of progenitor populations in which expression of DeltaN-p63 contributes to the preservation of self-renewing capacity. Our previous studies indicate that DeltaN-p63 is a transcriptional target of p53, however, the absence of overt epithelial deficiencies in p53-/- mice and reports of increased expression of DeltaN-p63 in p53-/- mice suggest p53-independent mechanisms also contribute to expression of DeltaN-p63. Here, we present data indicating that, prolonged loss of p53 leads to the activation of a p53-independent mechanism for transcriptional regulation of DeltaN-p63. This p53-independent mechanism is sensitive to ectopic p53 but not to a p53 mutant that lacks the transactivation domain. We further show that in cells in which p53 is expressed TA-p63-gamma protein is destabilized in a manner that is p53 dependent and sensitive to pharmacologic inhibition of the 26S proteosome. Consistent with this observation, we demonstrate that loss of p53 leads to the stabilization of TA-p63-gamma that is reversible by ectopic p53. Finally, we present evidence that disruption of TA-p63-gamma expression leads to decreased expression of DeltaN-p63 and that overexpression of TA-p63-gamma was sufficient to enhance the activity of the DeltaN-p63 promoter. Taken together, our studies indicate that TA-p63-gamma is capable of activating expression of DeltaN-p63 and that this mechanism may account for p53-independent expression of DeltaN-p63.