Targeting colorectal cancer via its microenvironment by inhibiting IGF-1 receptor-insulin receptor substrate and STAT3 signaling.

The tumor microenvironment (TME) exerts critical pro-tumorigenic effects through cytokines and growth factors that support cancer cell proliferation, survival, motility and invasion. Insulin-like growth factor-1 (IGF-1) and signal transducer and activator of transcription 3 (STAT3) stimulate colorectal cancer development and progression via cell autonomous and microenvironmental effects. Using a unique inhibitor, NT157, which targets both IGF-1 receptor (IGF-1R) and STAT3, we show that these pathways regulate many TME functions associated with sporadic colonic tumorigenesis in CPC-APC mice, in which cancer development is driven by loss of the Apc tumor suppressor gene. NT157 causes a substantial reduction in tumor burden by affecting cancer cells, cancer-associated fibroblasts (CAF) and myeloid cells. Decreased cancer cell proliferation and increased apoptosis were accompanied by inhibition of CAF activation and decreased inflammation. Furthermore, NT157 inhibited expression of pro-tumorigenic cytokines, chemokines and growth factors, including IL-6, IL-11 and IL-23 as well as CCL2, CCL5, CXCL7, CXCL5, ICAM1 and TGFβ; decreased cancer cell migratory activity and reduced their proliferation in the liver. NT157 represents a new class of anti-cancer drugs that affect both the malignant cell and its supportive microenvironment

Diffusion and Home Range Parameters from Rodent Population Measurements in Panama

Simple random walk considerations are used to interpret rodent population data collected in Hantavirus-related investigations in Panama regarding the short-tailed cane mouse, \emph{Zygodontomys brevicauda}. The diffusion constant of mice is evaluated to be of the order of (and larger than) 200 meters squared per day. The investigation also shows that the rodent mean square displacement saturates in time, indicating the existence of a spatial scale which could, in principle, be the home range of the rodents. This home range is concluded to be of the order of 70 meters. Theoretical analysis is provided for interpreting animal movement data in terms of an interplay of the home ranges, the diffusion constant, and the size of the grid used to monitor the movement. The study gives impetus to a substantial modification of existing theory of the spread of the Hantavirus epidemic which has been based on simple diffusive motion of the rodents, and additionally emphasizes the importance for developing more accurate techniques for the measurement of rodent movement.Comment: 18 pages, 5 figure

Recovery Research, Katrina's Fifth Anniversary, and Lessons Relearned

What may be called “disaster science” is a broad field that begins with understanding hazards, risks, and population vulnerabilities and moves on to establishing best-practice models of response, mitigation, and recovery. Gaps abound in our collective knowledge in all of these areas, and it is fair to suggest that we have only begun to scratch the surface in terms of what we need to know. The goal continues to be to learn how to prevent disasters whenever possible and, when prevention is not possible, to at least optimize survival, preserve vital infrastructure, and return rapidly to a state of normalcy

Hurricane Sandy: Lessons Learned, Again

Hurricane Sandy was a sobering reminder to those of us who call New York home that it is a port city and subject to the whims of wind and water. The storm itself was massive: climatologically, a thousand miles wide at its peak; economically, an estimated excess of $50 billion in damages. In the New York metropolitan area, 97 people died in the storm, thousands were displaced from their homes, and 2 major hospitals required perilous evacuations even as the hurricane force winds engulfed the metropolitan region. For those of us in the fields of disaster medicine and public health preparedness, the question is, were we ready? During the past decade considerable public investment has been made in standardizing command and communication, assuring appropriate and rapid supply chains, and training the medical and public health workforces to respond appropriately. And yet, in the week after the storm, persistent reports of widespread gaps in the provision of coordinated relief were received from the Rockaways to Coney Island to Staten Island and New Jersey. The question was not one of capacity and capability as much as it was of communication and coordination. Resources did not always make it the last mile to reach those most in need