NASA Scientific and Technical Aerospace Reports

20040111622 Texas Univ., Houston, TX
A High Resolution Clinical PET with Breast and Whole Body Transfigurations
Wong, Wai-Hoi; Apr. 2004; 14 pp.; In English; Original contains color illustrations
Contract(s)/Grant(s): DAMD17-02-1-0461
Report No.(s): AD-A425721; No Copyright; Avail: CASI; A03, Hardcopy
Despite advances in the last decade, the radiographic diagnosis of breast cancer remains uncertain. Of the annual 600,000
cases referred for biopsy by mammograms each year, 400,000 are unnecessary, costing $2 billion annually. The diagnosis of
breast cancer in young women and women with silicone implants continues to be difficult. Accurate detection of small breast
tumors (2-3 mm) is still to be achieved. Positron emission tomography (PET) has the potential to reduce this high healthcare
cost, unnecessary painful anxiety, and to improve diagnosis and survivability for women of all ages. We have developed the
detector and electronic technology for building an ultrahigh resolution PET camera. We propose to use such technology to
construct an ultrahigh resolution PET that has a dedicated breast- diagnosis mode that has 13-26 times higher detection
sensitivity than regular PET and an ultrahigh Image resolution of 2. 5mm compared to the 4.5-6 mm in today’s PET cameras.
We have already developed a scaled-down engineering prototype PET to confirm the feasibility that 2-3 mm tumor can be
detected accurately. We propose to construct a scaled-up clinical version of the design so that it can be used for clinical human
trials to confirm the clinical utility.
DTIC
Cancer; High Resolution; Mammary Glands; Positrons; Tomography
20040111623 Tulane Univ., New Orleans, LA
Retroelements and Genetic Instability in Breast Cancer
Belancio, Victoria P.; Deininger, Prescott L.; Apr. 2004; 22 pp.; In English
Contract(s)/Grant(s): DAMD17-02-1-0597
Report No.(s): AD-A425722; No Copyright; Avail: CASI; A03, Hardcopy
LINEl is a mammalian retroelement that contributes to genomic instability. The full extent of LINE-i mobility in somatic
tissues and tumors is not known. L1 expression is extremely low in differentiated cells except for testis, but it is significantly
elevated in breast malignancies. This suggests that posttranscriptional mechanisms are involved in limitation of L1 expression.
We demonstrated that the use of the polyA sites located within the L1.3 genome limits the amount of full-length L1.3 mRNAs.
L1 polyA signals can be functional when fragments of L1.3 element are inserted into 3’ UTRs of genes. This unique
attenuation mechanism helps to minimize the rate of L1 retrotransposition, but may also increase the negative impact of these
insertion events on the genome after their insertion. Human EST database searches suggest that the polyA signals may also
play a role in regulation of L1 expression in a tissue and/or tumor specific manner with breast cancer tissues supporting the
least efficient L1 polyadenylation. The EST data are strengthened by significant differences in the L1 RNA profiles between
transiently transfected breast cancer and nonbreast cancer cell lines. These observations suggest a potential global change in
the mechanism of polyadenylation process upon malignant transformation of mammary gland.
DTIC
Cancer; Genetics; Mammary Glands
20040111624 Pennsylvania Univ., Philadelphia, PA
Immunotherapy of Breast Cancer Using Novel Her2/neu-Based Vaccines
Maciag, Paulo; Apr. 2004; 9 pp.; In English; Original contains color illustrations
Contract(s)/Grant(s): DAMD17-02-1-0545
Report No.(s): AD-A425723; No Copyright; Avail: CASI; A02, Hardcopy
Breast cancer is the most common malignancy in women. In U.S., 180,000 new cases are diagnosed and 45,000 deaths
occur each year, Current therapy for this disease is aggressive and frequently mulitating. We have been developing a Listeria
monocytogenes based Her2/neu vaccine for breast cancer. L. monocytogenes has been successfully used as a vaccine vector
and tested in several disease models. To improve our immunotherapeutic approach to breast cancer, we are currently
investigating the NY-ESO-l antigen, which is expressed in a large proportion of breast cancers. NY-ESO-l is the most
immunogenic member of the Cancer-Testis antigen family. It is now widely accepted that tumors can escape immunotherapies
targeting a single antigen by losing expression of that antigen. In this case, association of Her2/neu and NY-ESO-l could
provide a more efficient vaccine against breast cancer. In this study, we constructed several NY-ESO-l recombinant-Listeria
- monocytogenes. We found that the C-term region of NY-ESO-1, which contains the important HLA-A2/l57-165 epitope, is
poorly secreted by Listeria. We are also generating a NT-2 (her2/neu positive) and 4T1-based breast cancer models in the
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