Lifetime exposure to a soluble TGF-beta antagonist protects mice against metastasis without adverse side effects.

TGF-betas play diverse and complex roles in many biological processes. In tumorigenesis, they can function either as tumor suppressors or as pro-oncogenic factors, depending on the stage of the disease. We have developed transgenic mice expressing a TGF-beta antagonist of the soluble type II TGF-beta receptor:Fc fusion protein class, under the regulation of the mammary-selective MMTV-LTR promoter/enhancer. Biologically significant levels of antagonist were detectable in the serum and most tissues of this mouse line. The mice were resistant to the development of metastases at multiple organ sites when compared with wild-type controls, both in a tail vein metastasis assay using isogenic melanoma cells and in crosses with the MMTV-neu transgenic mouse model of metastatic breast cancer. Importantly, metastasis from endogenous mammary tumors was suppressed without any enhancement of primary tumorigenesis. Furthermore, aged transgenic mice did not exhibit the severe pathology characteristic of TGF-beta null mice, despite lifetime exposure to the antagonist. The data suggest that in vivo the antagonist may selectively neutralize the undesirable TGF-beta associated with metastasis, while sparing the regulatory roles of TGF-betas in normal tissues. Thus this soluble TGF-beta antagonist has potential for long-term clinical use in the prevention of metastasis.

Using the hierarchy of control technologies to improve healthcare facility infection control: lessons from severe acute respiratory syndrome.

Health care facilities need to review their infection control plans to prepare for the possible resurgence of severe acute respiratory syndrome, other emerging pathogens, familiar infectious agents such as tuberculosis and influenza, and bioterrorist threats. This article describes the classic "hierarchy of control technologies" that was successfully used by occupational and environmental medicine professionals to protect workers from illness and death during the resurgence of tuberculosis in the 1990s. Also discussed are related guidelines from building and equipment professional organizations and novel infection control techniques used successfully by various hospitals in Asia, Canada, and the United States during the 2003 severe acute respiratory syndrome epidemic. Taken together, they suggest a framework upon which a comprehensive infection control plan can be crafted to prevent the spread of deadly infectious agents to health care workers (clinicians and paraprofessionals), uninfected patients and visitors.