Periostin cooperates with mutant p53 to mediate invasion through the induction of STAT1 signaling in the esophageal tumor microenvironment.

Periostin (POSTN), a matricellular protein, has been reported to be important in supporting tumor cell dissemination. However, the molecular mechanisms underlying POSTN function within the tumor microenvironment are poorly understood. In this study, we observe that the inducible knockdown of POSTN decreases esophageal squamous cell carcinoma (ESCC) tumor growth in vivo and demonstrate that POSTN cooperates with a conformational missense p53 mutation to enhance invasion. Pathway analyses reveal that invasive esophageal cells expressing POSTN and p53(R175H) mutation display activation of signal transducer and activator of transcription 1 (STAT1) target genes, suggesting that the induction of STAT1 and STAT1-related genes could foster a permissive microenvironment that facilitates invasion of esophageal epithelial cells into the extracellular matrix. Genetic knockdown of STAT1 in transformed esophageal epithelial cells underscores the importance of STAT1 in promoting invasion. Furthermore, we find that STAT1 is activated in ESCC xenograft tumors, but this activation is attenuated with inducible knockdown of POSTN in ESCC tumors. Overall, these results highlight the novel molecular mechanisms supporting the capacity of POSTN in mediating tumor invasion during ESCC development and have implications of therapeutic strategies targeting the tumor microenvironment.

Validation of a new virtual wedge model.

Results of a validation study of a commercial virtual wedge device recently installed at our institution are presented. The wedge simulation produces an energy fluence from the treatment head that is equivalent to the primary energy fluence attenuated through a wedge-shaped slab of water with the central axis fluence set to unity. A simple exponential formula used to compute off-axis wedge factors is compared to beam profiles measured in a water phantom. A fast Fourier transform (FFT) convolution dose calculation is compared to measured dose profiles. Measured and calculated central axis wedged/open field ratios as a function of depth are also compared.

Realization and verification of three-dimensional conformal radiotherapy with modulated fields.

PURPOSE: We describe the experimental demonstration of the delivery of a three-dimensional conformal radiotherapy dose distribution using in-field modulation of nine fixed-gantry fields. METHODS AND MATERIALS: Two-dimensional in-field modulation profiles, varying from field to field, were realized by quasi-dynamic multileaf collimation using the prototype of a commercially available multileaf collimator installed on a medical linear accelerator. The profiles were calculated to deliver an optimal dose distribution for a patient with a prostate carcinoma. The target volume surface was invaginated and bifurcated. The calculated dose distribution was delivered to a homogeneous polystyrene phantom consisting of 1 cm thick slices that were cut to match the patient's outer contour. Seven therapy verification films were placed between the phantom slices. RESULTS: Analysis of the films revealed a degree of conformation of the high-dose region to the target shape that would not be possible with unmodulated conformal therapy. However, small observed spatial displacements of the dose distribution confirm the need for very accurate positioning. CONCLUSIONS: It is feasible to deliver clinically relevant, three-dimensional dose distributions that conform to invaginated and bifurcated target volumes using fields modulated by multileaf collimators.

X-ray field compensation with multileaf collimators.

PURPOSE: It has been proposed that conformal therapy can be carried out with static ports that are each individually compensated to deliver an optimal total dose distribution. If this proposal is to be implemented, one must have a means of compensating or modulating the fluence distributions within the boundaries of individual treatment fields. A theory was developed and implemented to achieve this goal. METHODS AND MATERIALS: The theory allowed creation of a leaf-setting sequence for a desired level of field-modulation precision. This method of beam modulation was experimentally verified using radiographic film to integrate the dose delivered by the sequence of discrete static multileaf collimator-defined subfields. RESULTS: Beam profiles were generated that matched the planned beam profiles to within the specified degree of precision. CONCLUSION: This methodology is a candidate for implementation of inverse planning for conformal therapy.

Clinical dosimetry for implementation of a multileaf collimator.

In order to initiate the use of a multileaf collimator (MLC) in the clinic, a set of technical procedures needs to be available sufficient to create MLC leaf settings and to deliver an accurate dose of radiation through the MLC-shaped field. Dosimetry data for clinical use of the MLC were measured. Dosimetric characteristics included central axis percent depth dose, output factors, and penumbra. In this paper, it has been concluded that a dose control monitor unit calculation procedure that has been applied to the use of conventional secondary field-shaping blocks can be applied to the multileaf collimator dosimetry. The multileaf collimator penumbra (20% to 80%) is only slightly wider (1-3 mm) than the penumbra of the conventional collimator jaws. Beam's-eye-view comparisons made between the isodose curves in fields shaped by conventional Cerrobend blocks and isodose curves in fields shaped by the multileaf collimator demonstrated that the 50% isodose line at 10-cm depth exhibited the discrete steps of the multileaf collimator leaves, but that the 90% and 10% isodose curves of the multileaf were close to those shaped by Cerrobend blocks.