Scott S. Williams

Breast-conserving radiation therapy using combined electron and intensity-modulated radiotherapy technique

BACKGROUND AND PURPOSE To explore the feasibility of a multi-modality breast-conserving radiation therapy treatment technique to reduce high dose to the ipsilateral lung and the heart when compared with the conventional treatment technique using two tangential fields. MATERIALS AND METHODS An electron beam with appropriate energy was combined with four intensity modulated photon beams. The direction of the electron beam was chosen to be tilted 10-20 degrees laterally from the anteroposterior direction. Two of the intensity-modulated photon beams had the same gantry angles as the conventional tangential fields, whereas the other two beams were rotated 15-25 degrees toward the anteroposterior directions from the first two photon beams. An iterative algorithm was developed which optimizes the weight of the electron beam as well as the fluence profiles of the photon beams for a given patient. Two breast cancer patients with early-stage breast tumors were planned with the new technique and the results were compared with those from 3D planning using tangential fields as well as 9-field intensity-modulated radiotherapy (IMRT) techniques. RESULTS The combined electron and IMRT plans showed better dose conformity to the target with significantly reduced dose to the ipsilateral lung and, in the case of the left-breast patient, reduced dose to the heart, than the tangential field plans. In both the right-sided and left-sided breast plans, the dose to other normal structures was similar to that from conventional plans and was much smaller than that from the 9-field IMRT plans. The optimized electron beam provided between 70 to 80% of the prescribed dose at the depth of maximum dose of the electron beam. CONCLUSIONS The combined electron and IMRT technique showed improvement over the conventional treatment technique using tangential fields with reduced dose to the ipsilateral lung and the heart. The customized beam directions of the four IMRT fields also kept the dose to other critical structures to a minimum.

Human inflammatory cells within the tumor microenvironment of lung tumor xenografts mediate tumor growth suppression in situ that depends on and is augmented by interleukin-12

The human tumor microenvironment includes a mixture of tumor cells, inflammatory cells, fibroblasts, and endothelial cells, all of which are tethered to an extracellular matrix. It has been difficult to study the dynamic interactions of these cells in human tumors in situ for obvious ethical and logistical considerations that prohibit experimental manipulations of tumors while still in patients. Fresh tissue from human lung tumor biopsy implanted into SCID mice was shown to remain viable, and the histologic appearance of the tumor microenvironment was maintained in the tumor xenografts for at least 3 months. In this study, the authors established that the inflammatory cells within human tumor xenografts can suppress tumor growth, and that this suppression is a result, in part, of endogenously produced interleukin-12 (IL-12) because IL-12 neutralizing antibodies enhance the growth of the tumor xenografts. The tumor-inhibitory activity of the inflammatory leukocytes is also enhanced by the local and sustained release of human recombinant IL-12 into the tumor microenvironment from cytokine-loaded biodegradable microspheres. Neither the anti–IL-12 neutralizing antibody nor the delivery of exogenous IL-12 from microspheres had any effect on tumor xenografts in the absence of the inflammatory leukocytes. In conclusion, the inflammatory cells within the tumor microenvironment of human lung tumor xenografts are functional and can suppress tumor growth, and the dynamic effects of the inflammatory cells can be modulated by exogenous cytokines.

VH and VL Gene Complexes Encoding an Anti-Spectrin Antibody are Defined by Nucleotide Sequencing of cDNA from a Hybridoma Generated from Hu-PBL-SCID Mouse

Previously we reported that human imunocompetent cells engrafted into scid mice mount a sustained and vigorous humoral immune response to murine erythrocytes. One of the dominant and consistently observed reactivity pattern of these antibodies in immunoblot analysis is with the alpha and beta isoforms of spectrin. In order to define the human xenoreactive response more completely, a hybridoma was generated (from a hu-PBL-scid mouse) whose antibody reacted with two high molecular weight species 225 to 250 kDa. We report here that this conserved antibody species reacts with both the murine and human erythrocyte proteins and cDNA nucleotide sequence analysis of the light and heavy chain genes encoding this antibody reveals that the light chain variable region gene has been previously observed in association with an autoreactive antibody. In addition to characterizing a conserved human B cell clonotype this is the first report of a human monoclonal antibody being generated from the hu-PBL-scid model using the standard hybridoma technology.