Adjustment of the lateral and longitudinal size of scanned proton beam spots using a pre-absorber to optimize penumbrae and delivery efficiency

In scanned-beam proton therapy, the beam spot properties, such as the lateral and longitudinal size and the minimum achievable range, are influenced by beam optics, scattering media and drift spaces in the treatment unit. Currently available spot scanning systems offer fewoptions for adjusting these properties. We investigated a method for adjusting the lateral and longitudinal spot size that utilizes downstream plastic pre-absorbers located near a water phantom. The spot size adjustment was characterized usingMonte Carlo simulations of a modified commercial scanned-beam treatment head. Our results revealed that the pre-absorbers can be used to reduce the lateral full width at half maximum (FWHM) of dose spots inwater by up to 14 mm, and to increase the longitudinal extent from about 1 mm to 5 mm at residual ranges of 4 cm and less. A large factor in manipulating the lateral spot sizes is the drift space between the preabsorber and the water phantom. Increasing the drift space from 0 cm to 15 cm leads to an increase in the lateral FWHM from 2.15 cm to 2.87 cm, at a waterequivalent depth of 1 cm. These findings suggest that this spot adjustment method may improve the quality of spot-scanned proton treatments. © 2010 Institute of Physics and Engineering in Medicine

ERK5 Is Required for Tumor Growth and Maintenance Through Regulation of the Extracellular Matrix in Triple Negative Breast Cancer

Conventional mitogen-activated protein kinase (MAPK) family members regulate diverse cellular processes involved in tumor initiation and progression, yet the role of ERK5 in cancer biology is not fully understood. Triple-negative breast cancer (TNBC) presents a clinical challenge due to the aggressive nature of the disease and a lack of targeted therapies. ERK5 signaling contributes to drug resistance and metastatic progression through distinct mechanisms, including activation of epithelial-to-mesenchymal transition (EMT). More recently a role for ERK5 in regulation of the extracellular matrix (ECM) has been proposed, and here we investigated the necessity of ERK5 in TNBC tumor formation. Depletion of ERK5 expression using the CRISPR/Cas9 system in MDA-MB-231 and Hs-578T cells resulted in loss of mesenchymal features, as observed through gene expression profile and cell morphology, and suppressed TNBC cell migration. In vivo xenograft experiments revealed ERK5 knockout disrupted tumor growth kinetics, which was restored using high concentration Matrigel™ and ERK5-ko reduced expression of the angiogenesis marker CD31. These findings implicated a role for ERK5 in the extracellular matrix (ECM) and matrix integrity. RNA-sequencing analyses demonstrated downregulation of matrix-associated genes, integrins, and pro-angiogenic factors in ERK5-ko cells. Tissue decellularization combined with cryo-SEM and interrogation of biomechanical properties revealed that ERK5-ko resulted in loss of key ECM fiber alignment and mechanosensing capabilities in breast cancer xenografts compared to parental wild-type cells. In this study, we identified a novel role for ERK5 in tumor growth kinetics through modulation of the ECM and angiogenesis axis in breast cancer