Scientific and Technical Aerospace Reports Volume 39 April 6, 2001

ations found in clinical and genetic data from the NNFF International Database with logistic regression, multivariate probit models,
generalized estimating equations, and multivariate normal models. These sophisticated techniques allowed us to adjust for
the complex and pervasive effect of age and other covariates that confounded previous studies. We showed that certain clinical
features of NF1 cluster in particular patients and within affected families. We also began our analysis of NF1 allele-phenotype
associations and used the large deletion phenotype in a proof of principle for the method developed for this project. Our results
demonstrate the importance of genetic factors in determining not only whether an individual will have NF1 but also what clinical
features of the disease will develop.
DTIC
Clinical Medicine; Genetics; Multivariate Statistical Analysis; Epidemiology
20010026189 Garvan Inst. of Medical Research, Darlinghurst, Australia
Investigation of the Role of the Mitogenic Neuropeptide Galanin in Mammary Gland Development and Carcinogenesis
Annual Report, 1 Aug. 1999-31 Jul. 2000
Ormandy, Christopher, Garvan Inst. of Medical Research, Australia; Naylor, Matthew J., Garvan Inst. of Medical Research,
Australia; Aug. 2000; 27p; In English
Contract(s)/Grant(s): DAMD17-99-1-9185
Report No.(s): AD-A385952; No Copyright; Avail: CASI; A01, Microfiche; A03, Hardcopy
Mammary gland development in the galanin knockout mouse has been the focus of activity during the previous year. The
galanin knockout was found to show failure of mammary development during the first pregnancy which resulted in a 100% failure
of lactation. Subsequent pregnancies resulted in normal development and successful lactation. Mammary gland recombination/
transplantation showed that this effect was not mammary epithelial cell autonomous, and did not require stromal galanin, ruling
out an autocrine role for galanin. Analysis of the galanin receptor 1 knockout revealed no lactational deficit, ruling out an autocrine
role for galanin via this receptor. An endocrine role via the other receptors is currently under investigation using whole mammary
gland organ culture Similarity to the prolactin knockout phenotype suggested prolactin as a mediator of an indirect effect of galanin,
and attempts to rescue developmental failure with osmotic minipump administration of prolactin were successful. The expression
pattern of galanin and its receptors is under investigation at various stages of mouse mammary development. Studies in human
material have used cell lines to date, where the expression patterns of galanin and its receptors have been determined, allowing
the selection of suitable cell lines for in vitro analysis of the potential growth promoting action of galanin. Experiments using 96
well plate MTT proliferation assays have proved difficult due to variability of response, and ongoing work has shifted to the use
of clonogenic assays. The formation of arrayed human breast cancer biopsies has begun to allow the analysis of galanin expression
during disease progression. The mouse work is currently being prepared for publication. During these experiments observations
were made regarding the role of the mouse stroma in the control of mammary ductal branching patterns and a brief communication
has been prepared and submitted for publication.
DTIC
Mammary Glands; Cancer; Peptides; Cells (Biology); Assaying; Mice; Endocrinology
20010026216 Georgetown Univ., Medical Center, Washington, DC USA
Characterization of Early Genomic Changes in Mammary Glands of High Risk Women Annual Report, 1 Jul. 1999-30
Jun. 2000
Dickson, Robert, Georgetown Univ., USA; Jul. 2000; 12p; In English
Contract(s)/Grant(s): DAMD17-99-1-9193
Report No.(s): AD-A385938; No Copyright; Avail: CASI; A01, Microfiche; A03, Hardcopy
Because many of the familial breast cancer patients carry a mutation in BRCA-1 on chromosome 17 or BRCA-2 on chromosome
13, the first genetic event that may occur in their mammary glands to begin the progression toward cancer is on one of these
two chromosomes. This genetic event is termed loss of heterozygosity (LOH). It is unknown if these genetic changes correspond
to a recognizable histopathological abnormality, nor what are the precise associated chromosomal changes leading to cancer. At
the Lombardi Cancer Center, we have a large ongoing study to test high-risk women for BRCA mutations and to counsel them
on their prevention options. One of the options is prophylactic mastectomy, and our Histopathology and Tissue Shared Resource
is maintaining a repository and database, with associated blood specimens of such material. We now propose to utilize these ’normal
glands’ removed for preventive purposes, as well as BRCA-positive breast cancer and associated mastectomy tissue to learn
more about the precise earliest histopathologic changes and associated chromosomal changes in BRCA-carriers. From these stud-
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