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Immunologic and Biologic Properties of the Primary Tumor During Prolonged Neoadjuvant Chemoimmunotherapy

Patients with locally advanced cancers have a poor prognosis when treated with radiotherapy and/or surgery alone. The appearance of distant metastases shortly after removal of the primary tumor indicates that micrometastases are already present at the time of diagnosis. We observed a favorable outcome in patients with locally advanced breast cancer treated with a prolonged regimen of neoadjuvant chemotherapy plus granulocyte-macrophage colony-stimulating factor (GM-CSF [Leukine]) compared with patients receiving fewer chemotherapy cycles prior to surgery and radiotherapy. These results can partly be explained by the dose-intensive regimen used, but biologic and immunologic processes inherent to the prolonged presence of the primary tumor and its draining lymph nodes might also contribute to the beneficial outcome. The effects of the prolonged presence of the primary tumor during chemotherapy and GM-CSF administration on the antitumor immune response, and more specifically the functional properties of dendritic cells and T cells, are currently being investigated in a multicenter randomized clinical trial comparing prolonged neoadjuvant chemotherapy plus cytokines with a conventional treatment schedule. Aside from investigations concerning the immune system, other biologic processes, such as tumor angiogenesis, are being investigated at the same time. [ONCOLOGY 16(Suppl 1):32-39, 2002]

Latest Article

Proteomics to Diagnose Human Tumors and Provide Prognostic Information

Proteomics is a rapidly emerging scientific discipline that holds greatpromise in identifying novel diagnostic and prognostic biomarkers forhuman cancer. Technologic improvements have made it possible to profileand compare the protein composition within defined populationsof cells. Laser capture microdissection is a tool for procuring pure populationsof cells from human tissue sections to be used for downstreamproteomic analysis. Two-dimensional polyacrylamide gel electrophoresis(2D-PAGE) has been used traditionally to separate complex mixturesof proteins. Improvements in this technology have greatly enhancedresolution and sensitivity providing a more reproducible and comprehensivesurvey. Image analysis software and robotic instrumentationhave been developed to facilitate comparisons of complex protein expressionpatterns and isolation of differentially expressed proteins spots.Differential in-gel electrophoresis (DIGE) facilitates protein expressionby labeling different populations of proteins with fluorescent dyes.Isotope-coded affinity tagging (ICAT) uses mass spectroscopy for proteinseparation and different isotope tags for distinguishing populationsof proteins. Although in the past proteomics has been primarilyused for discovery, significant efforts are being made to developproteomic technologies into clinical tools. Reverse-phase protein arraysoffer a robust new method of quantitatively assessing expressionlevels and the activation status of a panel of proteins. Surface-enhancedlaser-desorption/ionization time-of-flight (SELDI-TOF) mass spectroscopyrapidly assesses complex protein mixtures in tissue or serum. Combinedwith artificial intelligence–based pattern recognition algorithms,this emerging technology can generate highly accurate diagnostic information.It is likely that mass spectroscopy–based serum proteomicswill evolve into useful clinical tools for the detection and treatment ofhuman cancers.