Abstract

Mesotheliomas are hypothesized to develop in response to fibers of critical dimensions. A new model for the induction of mesotheliomas in mice has been developed. Discrete peritoneal nodules develop in response to asbestos, but not to toxic silica particles or nontoxic titanium dioxide particles. Under these conditions, peritoneal macrophages are persistently activated. This model will be used to explore the histogenesis of mesotheliomas and investigate the role of activated macrophages in the development of these tumors. Energy-dispersive x-ray analysis and electron microscopy will be used to determine whether the surface or size of asbestos fibers become modified in vitro. Immunocytochemical typing of intermediate filaments and microspectrofluorimetric assay of DNA content will be used to identify possible precursor lesions of mesotheliomas. Finally, the role of activated macrophages in stimulating proliferation of possible precursor populations and mesotheliomas will be evaluated.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Research Project (R01)
Project #
1R01ES003721-01
Application #
3251300
Study Section
Pathology B Study Section (PTHB)
Project Start
1985-06-15
Project End
1988-05-31
Budget Start
1985-06-15
Budget End
1986-05-31
Support Year
1
Fiscal Year
1985
Total Cost
Indirect Cost

  Institution

Name
Brown University
Department
Type
Schools of Medicine
DUNS #
001785542
City
Providence
State
RI
Country
United States
Zip Code

  Publications

Sarin, Love; Sanchez, Vanesa C; Yan, Aihui et al. (2010) Selenium-carbon bifunctional nanoparticles for the treatment of malignant mesothelioma. Adv Mater 22:5207-11
Miselis, Nathan R; Lau, Bonnie W; Wu, Zhijin et al. (2010) Kinetics of host cell recruitment during dissemination of diffuse malignant peritoneal mesothelioma. Cancer Microenviron 4:39-50
Lau, Bonnie W; Kane, Agnes B (2010) SDF1/CXCL12 is involved in recruitment of stem-like progenitor cells to orthotopic murine malignant mesothelioma spheroids. Anticancer Res 30:2153-60
Altomare, Deborah A; Menges, Craig W; Pei, Jianming et al. (2009) Activated TNF-alpha/NF-kappaB signaling via down-regulation of Fas-associated factor 1 in asbestos-induced mesotheliomas from Arf knockout mice. Proc Natl Acad Sci U S A 106:3420-5
Sanchez, Vanesa C; Pietruska, Jodie R; Miselis, Nathan R et al. (2009) Biopersistence and potential adverse health impacts of fibrous nanomaterials: what have we learned from asbestos? Wiley Interdiscip Rev Nanomed Nanobiotechnol 1:511-29
Miselis, Nathan R; Wu, Zhijin J; Van Rooijen, Nico et al. (2008) Targeting tumor-associated macrophages in an orthotopic murine model of diffuse malignant mesothelioma. Mol Cancer Ther 7:788-99
Pietruska, Jodie R; Kane, Agnes B (2007) SV40 oncoproteins enhance asbestos-induced DNA double-strand breaks and abrogate senescence in murine mesothelial cells. Cancer Res 67:3637-45
Kane, Agnes B (2006) Animal models of malignant mesothelioma. Inhal Toxicol 18:1001-4
Altomare, Deborah A; You, Huihong; Xiao, Guang-Hui et al. (2005) Human and mouse mesotheliomas exhibit elevated AKT/PKB activity, which can be targeted pharmacologically to inhibit tumor cell growth. Oncogene 24:6080-9
Altomare, Deborah A; Vaslet, Charles A; Skele, Kristine L et al. (2005) A mouse model recapitulating molecular features of human mesothelioma. Cancer Res 65:8090-5

Showing the most recent 10 out of 21 publications