Inflammatory response is implicated as a biologic mechanism that links particulate matter (PM) air pollution with health effects. C-reactive protein (CRP), an important acutephase reactant with profound proinflammatory properties, is used clinically as an indicator of the presence and intensity of inflammation. In vitro and in vivo animal studies suggest that CRP levels increase in response to PM exposure, but there was no consistency in epidemiologic studies. Herein, a systematic review was conducted to examine the association between PM exposure and serum CRP levels in humans. Elevated CRP levels were consistently found among children, and CRP elevations were also observed among healthy adults, albeit requiring higher peak levels of PM exposure. PM-induced CRP responses were not consistently found in adults with chronic inflammatory conditions, perhaps because of the use of anti-inflammatory medications in this population. Of the eight examined randomized trials, only one trial with a longer intervention period supported the effect of PM exposure on CRP concentrations. To provide conclusive evidence, further epidemiologic studies are needed to better quantify the magnitude of CRP level changes in response to PM with well-defined study populations and better control of various confounding factors.

Thomsen-Friedenreich antigen (TF-Ag) is expressed in many carcinomas, including those of the breast, colon, bladder, and prostate. TF-Ag is important in adhesion and metastasis and as a potential immunotherapy target. We hypothesized that passive transfer of JAA-F11, an anti-TF-Ag monoclonal antibody, may create a survival advantage for patients with TF-Ag-expressing tumors by cytotoxicity, blocking of tumor cell adhesion, and inhibition of metastasis. This was tested using in vitro models of tumor cell growth; cytotoxicity assays; in vitro, ex vivo, and in vivo models of cancer metastasis; and, finally, in vivo effects in mice with metastatic breast cancer. Unlike some anti-TF-Ag antibodies, JAA-F11 did not enhance breast carcinoma cell growth. JAA-F11 did not induce the killing of 4T1 tumor cells through complement-dependent cytotoxicity or apoptotic mechanisms. However, JAA-F11 blocked the stages of metastasis that involve the adhesion of human breast carcinoma cells to human endothelial cells (human umbilical vein endothelial cells and human bone marrow endothelial cells 60) in in vitro static adhesion models, in a perfused ex vivo model, and in murine lung vasculature in an in vivo metastatic deposit formation assay. JAA-F11 significantly extended the median survival time of animals bearing metastatic 4T1 breast tumors and caused a > 50% inhibition of lung metastasis.