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View the Table of Contents for the September 1 issue of Clinical Cancer Research.
Martínez-Torrecuadrada et al. Page 6280
Fibroblast Growth Factor Receptor 3 (FGFR3) is mutated and overexpressed in a variety of human cancers, including bladder carcinomas. To explore its role as a therapeutic target for bladder carcinoma, Martínez-Torrecuadrada et al. have prepared and characterized a panel of human scFv fragments using phage display libraries to FGFR3α. Two scFvs, 3C and 7D, showed the capacity to bind wild-type and mutated FGFR3 and to compete with FGF9 and FGF1 for binding to this receptor. Moreover, they were able to block FGFR3-dependent proliferation of RT112 bladder carcinoma cells in a dose-dependent manner. These data support further evaluation of human scFvs anti-FGFR3 as anti-tumoral agents.
Van Houdt et al. Page 6400
Tumor cells can evade Granzyme B induced apoptosis via expression of PI-9. Van Houdt et al. found that PI-9 expression in tumor cells of stage III/IV melanoma patients treated with tumor vaccination therapy is an adverse prognostic marker. Although further investigation is needed to determine whether PI-9 is responsible for the failure of tumor vaccination, these data suggest that specific immune escape mechanisms may determine the clinical response to vaccination therapy. Adequate prediction of response to vaccination therapy may allow tailoring of therapy for the individual patient and improve the efficacy of vaccination trials.
Tehranchi et al. Page 6291
The combination of G-CSF and erythropoietin (Epo) may synergistically improve erythropoieses in myelodysplastic syndromes (MDS). To explore the molecular mechanism underlying this observation, Tehranchi et al. developed a method to detect erythroid apoptosis and the preferential growth of clones with cytogenetic abnormalities. Apoptosis was inhibited by G-CSF through all stages of differentiation and by Epo during the latter phase. Furthermore, Epo boosted growth of cytogenetically normal cells from 5q- patients, but not in monosomy 7 or trisomy 8 cells. Thus, this in vitro model may predict the responsiveness of MDS patients to recombinant growth factors, and could be useful for the testing of other erythropoietic therapies in these patients.
Shibata et al. Page 6109
Receptor activator of nuclear factor-κB ligand (RANKL) is a key mediator of osteoclastogenesis. B-cell lymphomas of bone origin develop bone destruction through unknown mechanisms. Shibata et al. explored RANKL expression and the mechanisms of osteoclastogenesis in B-lymphoid tumors. Some B-lymphoid cell lines as well as primary bone lymphoma cells aberrantly express RANKL as well as VEGF to enhance osteoclastogenesis. VEGF also recruits osteoclast precursors, and osteoclasts stimulate B-lymphoid tumor growth. Thus, the co-expression of RANKL and VEGF by B-lymphoid tumors may contribute to the close cellular interactions with osteoclasts to enhance bone destruction and tumor expansion in bone.
Viguier et al. Page 6212
There is increasing evidence of a relationship between the level of excision repair via ERCC1 and the response to chemotherapy. To investigate the effects of the synonymous ERCC1 C→T polymorphism at codon 118, Viguier et al. performed a retrospective study of patients treated with standard chemotherapy regimens for a metastatic colorectal cancer. The objective response rate to oxaliplatin in combination with 5-fluorouracil was significantly higher in the group of patients homozygous for the T allele that results in a decreased ERCC1 gene expression. This provides a promising molecular criterion to predict colorectal tumor sensitivity to oxaliplatin-containing regimens.