16 research outputs found
Transforming growth factor-β in breast cancer: too much, too late
The contribution of transforming growth factor (TGF)β to breast cancer has been studied from a myriad perspectives since seminal studies more than two decades ago. Although the action of TGFβ as a canonical tumor suppressor in breast is without a doubt, there is compelling evidence that TGFβ is frequently subverted in a malignant plexus that drives breast cancer. New knowledge that TGFβ regulates the DNA damage response, which underlies cancer therapy, reveals another facet of TGFβ biology that impedes cancer control. Too much TGFβ, too late in cancer progression is the fundamental motivation for pharmaceutical inhibition
Loco-regional differences in pulmonary function and density after partial rat lung irradiation
Purpose: The purpose of this study was to explore regional differences in radiosensitivity of rat lung Using lung function and computed tomography (CT) density as endpoints. Methods: At first, CT scans were used to determine rat lung, volumes. The data obtained enabled the design of accurate collimators to irradiate 50% of the total lung volume for the apex, base, left, right, mediastinal and lateral part of the lung. Male Wistar rats were irradiated with a single (lose of 18 Gy of orthovoltage X-rays. Further rat thorax CT scans were made before and 4, 16, 26, and 52 weeks after irradiation to measure ill Vivo lung density changes indicative of lung damage. To evaluate overall lung function, breathing frequencies were measured biweekly starting 1 week before irradiation. Results: Qualitative analysis of the CT scans showed clear density changes for all irradiated lung volumes, with the most prominent changes present in the mediastinal and left group at 26 weeks after radiation. Quantitative analysis using average density changes of whole lungs did not adequately describe the differences in radiation response between the treated groups. However. analysis of the density changes of the irradiated and non-irradiated regions of interest (ROI) more closely matched with the qualitative observations. Breathing frequencies (BF) were only increased after 50% left lung irradiation, indicating that the hypersensitivity of the mediastinal part as assessed by CT analysis, does not result in functional changes. Conclusions: For both BF and CT (best described by ROI analysis), differences in regional lung radiosensitivity were observed. The presentation Of lung damage either as function loss or density changes do not necessarily coincide, meaning that for each endpoint the regional sensitivity may be different. (C) 2003 Elsevier Ireland Ltd. All rights reserved