Fugitive Chemicals and Environmental Justice: A Model for Environmental Monitoring Following Climate-Related Disasters.

The combination of population growth in areas of mixed (residential, commercial, and industrial) land use along U.S. waterfronts and the increasing frequency of devastating hurricanes and storm surges has led to community fears of widespread toxic chemical contamination resulting from accidental industrial or small business releases, particularly in the aftermath of an extreme weather event, such as a hurricane. Industrial waterfront communities, which are frequently environmental justice communities, contain numerous toxic chemical sources located in close proximity to residential housing, schools, daycare centers, playgrounds, and healthcare centers. Despite the longstanding concerns of community activists and researchers about the potential for "fugitive" chemicals to be released into floodwaters, there has been little coordinated research or action to develop environmental monitoring programs for disaster-affected communities. In the aftermath of Superstorm Sandy, a community-academic partnership was formed between the New York City Environmental Justice Alliance, UPROSE, The LifeLine Group, and the RAND Corporation. The collaboration, known as Grassroots Research to Action in Sunset Park (GRASP) has focused on identifying possible sources of chemical contamination, modeling the potential for chemical release into community areas and resulting exposure risks, and proactively developing actions for mitigating or preventing adverse community impacts. Through our ongoing work, we have identified barriers and drivers for community-based environmental monitoring, and in doing so, we have developed a framework to overcome challenges. In this article, we describe this framework, which can be used by waterfront communities bracing to deal with the effects of future devastating weather disasters.

In vitro and in vivo pharmacology and pharmacokinetics of a human engineered monoclonal antibody to epithelial cell adhesion molecule.

ING-1(heMAb), a Human Engineered monoclonal antibody to epithelial cell adhesion molecule (Ep-CAM), was evaluated for its in vitro and in vivo activity. The dissociation constant of ING-1(heMAb) for binding to Ep-CAM on HT-29 human colon tumor cells was 2 to 5 nM, similar to chimeric ING-1. In antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity assays, ING-1(heMAb) caused a concentration-dependent lysis of BT-20 breast, MCF-7 breast, HT-29 colon, and CACO-2 colon tumor cells, with maximum cytolysis at approximately 1 microg/ml. After an intravenous injection in rats, plasma ING-1(heMAb) levels declined with an alpha half-life of 8 to 11 hours, and a beta half-life of 20 days, typical of an IgG in a species without the target for ING-1. In nude mice with human HT-29 colon tumors, plasma ING-1(heMAb) levels declined more rapidly than in non-tumor-bearing mice, suggesting an enhanced clearance via the tumor-associated human Ep-CAM. In nude mice, intravenous treatments with ING-1(heMAb) twice a week for 3 weeks significantly suppressed the growth of human HT-29 colon and PC-3 prostate tumors in a dose-dependent manner, with 1.0 mg/kg providing the greatest benefit. These results indicate that Human Engineered ING-1(heMAb) is a high-affinity antibody with potent in vitro activity that targets and suppresses the growth of human tumors in vivo.

ING-1(heMAb), a monoclonal antibody to epithelial cell adhesion molecule, inhibits tumor metastases in a murine cancer model.

ING-1(heMAb), a human-engineered monoclonal antibody (MAb) that specifically targets the epithelial cell adhesion molecule (Ep-CAM), kills adenocarcinoma cells in vitro and inhibits tumor growth in vivo. In the current study, we evaluated the efficacy of ING-1(heMAb) in a murine model of cancer metastases. Mice received intravenous dosing of 1 mg/kg ING-1(heMAb), twice a week, starting on day 2 or day 5. A negative control group received 1 mg/kg human immunoglobulin G with the same dose frequency starting on day 2. A positive control group received weekly 100 mg/kg 5-flurouracil/leucovorin starting on day 2. ING-1(heMAb)/day 2 treatment significantly reduced both the number of visible tumor nodules in body cavities (P <.01) and the number of metastases on lung surfaces (P <.005). The treatment also resulted in a 91% reduction of micrometastases in lung tissues (P <.0001). Delaying ING-1(heMAb) treatment until day 5 caused 54% reduction in micrometastases (P <.005). Our results indicate that a number of parameters, including treatment starting day, dose level, and dose frequency, are critical in achieving the optimal efficacy of ING-1(heMAb). We conclude that ING-1(heMAb) effectively reduced tumor metastases in a murine cancer model. Immunotherapy with ING-1(heMAb) may be beneficial in treating human metastatic diseases.