Progress 09/11/01 to 09/10/06
Outputs
The incidence of melanoma is rising rapidly, especially in the southwest. This research addresses the genetic parameters leading to the expression of melanoma and the physiological parameters producing spontaneous regression. The purpose of this research is to identify the genes responsible for the expression of melanoma, the specific role the genes play and the immunological mechanisms responsible for the spontaneous regression. With this information, final treatments will be developed. The overall objectives are to determine the cellular and molecular signals that initiate tumorigenesis and regression in a swine model of melanoma. The projects are: 1) to map and determine the genes responsible for expression of the tumor, 2) to determine the relative contribution of cytokines, macrophages and lymphocytes to regression, 3) to determine the roles of apoptosis and lack of telomerase to regression. A herd of Sinclair swine will be maintained from which tumor tissue and
white blood cells will be collected for use in various in vitro experiments. DNA will be used to map genes responsible for melanoma, once genes are identified and located, the role of that gene in causing the tumor will be investigated. As mechanisms are identified from the in vitro experiments, in vivo perturbations will be initiated to confirm and extend our observations. It is expected that the identification of a gene(s) involved in the expression and regression of these swine malignant melanomas will lead to the identification and control of proteins responsible. It is envisioned that as we identify the specific molecules responsible, it will provide unique avenues to accurately and succinctly design novel therapies for this devastating cancer. Use of the Sinclair swine/melanoma line has been successful and upon Dr. Amoss' retirement, the herd was transferred to the University of Nevada, Reno for continued research.
Impacts
It is expected that the identification of a gene(s) involved in the experession and regression of these swine malignant melanomas will lead to the identification and control of the proteins responsible. It is envisioned that as we identify the specific molecules responsible, it will provide unique avenues to accurately and succinctly design novel therapies for this devastating cancer.
Publications
- No publications reported this period
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Progress 01/01/03 to 12/31/03
Outputs
In collaboration with Drs. Yang Da, University of Minnesota and Craig Beattie, University of Nevada, Reno, a new mating plan was implemented in which back-crosses of tumor-positive F2 animals were made to tumor-positive Sinclair pigs. As expected, tumor incidence has increased in the offspring. We are currently analysing the numericasl data to determine if there are differences in tumor incidence that can be attributed to the haplotype of the original Sinclair animals. White blood cells have been isolated and frozen for future DNA analysis when all of the matings are complete.Drs. Yang Da, Craig beattie and myself are in the process of resubmitting a proposal to NCI entitled: Genetic Basis of Heritable malignant Melanoma of Swine. In collaboration with Dr. Doug Smith, Baylor Medical Center, Dalls, the typing of the major histocompatibility complex is ongoing. The first stage of this work has been published in the dissertation of Dr. Gregory W. Martens entitled: DNA
Based Typing of Swine Leukocyte Antigens. Dr. Smith's laboratory is continuing to type all of the offspring of the TAMU Sinclair Swine Research Herd. This laboratory is also collaborating with Dr. Gerald Cote', Texas A&M Engineering Experiment Station, in the development of high density photo-optical diagnostic technologies for the early detection of skin diseases, including melanoma.
Impacts
It is expected that the identification of a gene(s) involved in the experession and regression of these swine malignant melanomas will lead to the identification and control of the proteins responsible. It is envisioned that as we identify the specific molecules responsible, it will provide unique avenues to accurately and succinctly design novel therapies for this devastating cancer.
Publications
- Martens, Gregory W. DNA Based Typing of Swine Leukocyte Antigens. 2003. Dissertation, Insitute of Biomedical Studies, Baylor University.
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Progress 01/01/02 to 12/31/02
Outputs
A less than expected incidence of melanoma in the offspring of both the F1 and F2 generations has led us to a reevaluation of the hypothesized heredity of familial melanoma in this animal model. With the collaboration of Dr. Yang Da, Univ. of Minnesota, a new mating plan was conceived in order to test our new hypothesis. Along with Dr. Da , Dr. Craig Beattie and I have submitted a NCI proposal entitled: Genetic Basis of Heritable, Malignant Melanoma of Swine which is under consideration for funding in June, 2003. In collaboration with Dr. Sancy Leachman, University of Utah Medical School, we have shown using cDNA microarray analysis, that specific genes are being expressed during regression of the tumors. One gene, LGALS3BP, is differentially regulated when comparisons are made between the tumor in its progression and regression phases. This gene codes for a protein found in the serum of cancer patients that has the capability of stimulating host defense systems and
can induce the secretion of interleukin-2. This work is contiuing in order to identify which genes are being expressed and/or inhibited during progression and regression of these tumors. We have also collaborated with Dr. Doug Smith, Baylor Medical Center, Dallas, to determine the genetic differences in the swine major histocompatibilty complex among swine that express the melanoma and those that don't. These three projects all focus on the genetic potential inducing the expression and subsequent regression of these tumors. This laboratory is also collaborating with Dr. Gerald Cote, Texas A&M Engineering Experiment Station, in the development of high density photo-optical diagnosis of skin diseases including melanoma.
Impacts
It is expected that the identification of a gene(s) involved in the expression and regression of these tumors will lead to the identification and structure of the proteins responsible. It is envisioned that as we identify the specific molecules responsible, it will provide an avenue to accurate and succinctly design therapies for this cancer.
Publications
- Leachman SA, Hanson NW, Hinshaw J, Amoss M, Szabo A, Florell SR. cDNA Microarray Expression Profiling of Melanoma from Sinclair Miniature Swine. Pigment Cell Socoety, 2002. Abstract.
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Progress 01/01/01 to 12/31/01
Outputs
This year has been spent obtaining samples for future analysis. A total of 18 breeding pairs of F1s have been identified. According to the protocol this number will be reduced to 12 breeding pairs, 4 each of three different haplotype backgrounds. To date we have produced 147 F2s of which less than 10 have tumors. This may produce problems later during the analysis stage. A proposal entitled: "Genetic Ananlysis of an Animal Model of Melanoma" has been resubmitted and is under review by NCI for funding in April.
Impacts
(N/A)
Publications
- No publications reported this period
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