40 research outputs found

    CXCR4 expression on circulating pan-cytokeratin positive cells is associated with survival in patients with advanced non-small cell lung cancer

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    <p>Abstract</p> <p>Background</p> <p>The CXC chemokine, CXCL12, and its receptor, CXCR4 promote metastases of a variety of solid tumors, including non-small cell lung cancer (NSCLC). The expression of CXCR4 on tumor cells may represent a critical biomarker for their propensity to metastasize. This study was performed to evaluate the hypothesis that co-expression of pan-cytokeratin and CXCR4 may be a prognostic marker for patients with advanced NSCLC.</p> <p>Methods</p> <p>We evaluated CXCR4 levels on circulating pan-cytokeratin positive cells from patients with NSCLC. NSCLC tumor and metastases were also assessed for the presence of CXCR4.</p> <p>Results</p> <p>Pan-cytokeratin positive cells were increased in the circulation of patients with NSCLC, as compared to normal control subjects. Patients with pan-cytokeratin +/CXCR4+ = 2,500 cells/ml had a significant improvement in median survival when compared with patients with pan-cytokeratin +/CXCR4+ >2,500 cells/ml (not achieved versus 14 weeks). CXCR4 expression was found on NSCLC tumors and at sites of tumor metastasis.</p> <p>Conclusion</p> <p>This study suggests that CXCR4 may be a prognostic marker in NSCLC, and provides hypothesis-generating results, which may be important in determining metastatic potential. In future studies, we will prospectively evaluate the prognostic significance of pan-cytokeratin/CXCR4+ cells, and determine the mechanisms involved in the regulation of CXCR4 expression on tumor cells in a larger patient population.</p

    Minimal residual disease in breast cancer: an overview of circulating and disseminated tumour cells

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    Recombinant NY-ESO-1 protein with ISCOMATRIX adjuvant induces broad antibody responses in humans, a RAYS-based analysis

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    Antibody responses to tumor antigens play an important role in initiating a cellular antitumor response with respect to antigen cross-presentation and T cell cross-priming. Successful vaccination strategies rely on an optimally timed activation of the humoral and cellular immune system by using appropriate adjuvant stimulation. The LUD99-008 trial used the cancer testis antigen NY-ESO-1 formulated with ISCOMATRIX adjuvant injected into patients intramuscularly. It was shown that this vaccination strategy is a safe and highly potent activator of the humoral and cellular immune system. Using the RAYS technology, we analyzed in detail the humoral immune response in these patients before and after vaccination: during the course of repeated vaccinations with the adjuvant, antibody titers against NY-ESO-1 and cross-reactivity to LAGE 1A and B increased as an indicator of an enhanced immune response, whereas no antibody response could be detected after vaccination without the adjuvant. Analysis of single fragments of the NY-ESO-1 protein revealed that the humoral response was almost exclusively directed against the N-terminal fragments and the number of fragments and their length being recognized by the NY-ESO-1-specific antibodies increased during the course of vaccination. The humoral immune response mainly consisted of antibodies of the IgG1 and IgG3 subclass. We rarely found IgG2 and IgG4 subclass antibodies. Our results support the implication that target-specific antibodies raised after vaccination contribute to the stimulation of an effective T cell response against the target antigen
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