Molecular analysis of rat mammary carcinogenesis: An approach from carcinogenesis research to cancer prevention
Second Department of Pathology, Kansai Medical University, 10-15 Fumizono-cho, Moriguchi, Osaka, Japan.Medical Molecular Morphology (Impact Factor: 1.46). 01/2008; 40(4):185-90. DOI: 10.1007/s00795-007-0369-4
A rat strain carrying the human c-Ha-ras proto-oncogene is highly susceptible to chemically induced mammary carcinogenesis. All the transgenic rats develop preneoplastic mammary lesions within 20 days of an injection of N-methyl-N-nitrosourea, and mammary carcinomas appear within 8 weeks of treatment with a variety of chemical carcinogens. In this review, we summarize molecular aspects of mammary carcinogenesis in transgenic rats and the potential application of this model for studies of breast cancer prevention.
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ABSTRACT: Despite years of intensive investigation that has been made in understanding women's susceptibility to breast cancer, it remains a major cause of death worldwide. In mathematical terms, breast cancer can be outlined as a non-linear system that advances in time and in space through different states and a number of transitions from one state to another over a certain time interval. Breast cancer emerges from multiple spontaneous and/or inherited alterations that induce changes in expression patterns of genes and proteins that function in complex networks controlling critical cellular events. Here, we discuss breast cancer as a dynamical disease using the basic principles of the mathematics of non-linear systems and chaos theory. Additionally, some of the critical concepts necessary to give meaning to its underlying physical complexity are introduced. This way of thinking may help to clarify concepts, indicate alternative experiments and categorie the actual knowledge.
Article: Rat Resources in Biomedical Research[Show abstract] [Hide abstract]
ABSTRACT: The laboratory rat is obviously an important model for physiology, pathology, pharmacology, toxicology, and transplantation experiments. The value for pharmacological research is immense since virtually every drug approved for human treatment passes through the body of laboratory rats. Hundreds of unique rat models have been developed to mimic pathological and physiological human clinical conditions, especially in the case of complex diseases. Many of the model rats are deposited into rat resource centers, from which researchers can use and share animals and rat related resources in biomedical research. Recent progressing technologies for genetically engineered rats, such as traditional transgenesis, chemical ENU mutagenesis, and transposon insertional mutagenesis, will provide thousands of useful rat models for functional genomics and human diseases. Globally acting rat resource centers are prerequisites for successful and sustainable research in the biomedical field where the rats are used as model species.
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ABSTRACT: Breast cancer is the most frequent spontaneous malignancy diagnosed in women and is characterized by a broad histological diversity. Progression of the disease has a metastasizing trend and can be resistant to hormonal and chemotherapy. Animal models have provided some understanding of these features and have allowed new treatments to be proposed. However, these models need to be revised because they have some limitations in predicting the clinical efficacy of new therapies. In this review, we discuss the biological criteria to be taken into account for a realistic animal model of breast cancer graft (tumor implantation site, animal immune status, histological diversity, modern imaging). We emphasize the need for more stringent monitoring criteria, and suggest adopting the human RECIST (Response Evaluation Criteria in Solid Tumors) criteria to evaluate treatments in animal models.