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View the Table of Contents for the December 15 issue of Clinical Cancer Research.
Aghi et al. Page 8600
Epidermal growth factor receptor (EGFR) is overexpressed in a large proportion of human glioblastomas. A radiographic parameter distinguishing EGFR-amplified glioblastomas could enable preoperative identification of tumors responsive to EGFR-targeted therapies delivered during surgery, and might also better reflect downstream mediators of EGFR signaling than EGFR expression itself. Aghi et al. identified two MRI parameters altered in EGFR-amplified glioblastomas: (1) elevated T2/T1, the ratio of T2-bright to T1-enhanced volume; and (2) reduced T2-BSC (border sharpness coefficient), a novel parameter measuring the rate of change of grayscale intensities at T2-bright borders. These findings may reflect increased edema and/or invasiveness in EGFR-amplified glioblastoma.
Yauch et al. Page 8686
Significant improvements in the outcome of non-small cell lung carcinoma (NSCLC) have been reported in patients on treatment with the epidermal growth factor receptor (EGFR) inhibitor, erlotinib. Yauch et al. have identified a strong multi-gene signature indicative of an epithelial to mesenchymal transition (EMT) as a determinant of insensitivity to erlotinib in NSCLC cell lines. Further evaluation of the epithelial marker E-cadherin by immunohistochemistry in a clinical NSCLC trial showed that marker-positive patients exhibited a significantly longer time to progression when comparing erlotinib with chemotherapy treatment versus chemotherapy alone. These data support a potential role for EMT as a determinant of EGFR activity in NSCLC and E-cadherin expression as a novel biomarker predicting clinical activity of an EGFR inhibitor in NSCLC patients.
Fujita et al. Page 8837
The Y-box binding protein 1 (YB-1) regulates expression of P-glycoprotein (P-gp) encoded by the MDR1 gene. Although taxanes are known to be the substrates for P-gp, there have been no previous studies regarding the involvement of YB-1 in the development of resistance to taxanes. Fujita et al. investigated how paclitaxel affects the localization and expression of YB-1 in breast cancer and provided new information regarding the involvement of YB-1 in the development of resistance to taxanes both in vitro and in vivo.
Schewe et al. Page 8538
Studies on transactivation of genes via promoter elements have mostly been performed on cell lines rather than resected tissues. Schewe et al. present the first systematic study differentiating transcription factor–binding to two important regions of the u-PAR gene, a major molecule promoting invasion and metastasis, in 103 resected colorectal cancers and in normal tissues. An AP-1-promoter site appears as a less tumor-specific regulator than a combined Sp1/AP-2-motif. Data corroborate the hypothesis of synergism between both elements in resected tumors, however, and suggest first clinical prognostic conclusions.
Qian et al. Page 8808
To develop effective immunotherapies for patients with multiple myeloma (MM), it is important to use novel tumor antigens. Qian et al. obtained specific CTL lines after repeatedly stimulating T cells with autologous dendritic cells (DCs) pulsed with gp96 derived from myeloma cells. These T cells lysed gp96-pulsed DCs, myeloma cell lines U266, IM-9, and XG1, and primary myeloma cells from patients. The results also show that these T cells are potent CTLs that are able to effectively kill myeloma cells but not normal blood cells, and that heat shock proteins from allogeneic tumor cells may be used as vaccines to immunize patients.