Scientific and Technical Aerospace Reports Volume 39 April 6, 2001
Scientific and Technical Aerospace Reports Volume 39 April 6, 2001
Scientific and Technical Aerospace Reports Volume 39 April 6, 2001
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<strong>2001</strong>0025763 California Univ., Lawrence Berkeley Lab., Berkeley, CA USA<br />
MAPK-A Critical Intermediate in Anti-Estrogen Resistance Annual Report, 1 Sep. 1999-31 Aug. 2000<br />
Lupu, Ruth F.; Sep. 2000; 16p; In English<br />
Contract(s)/Grant(s): DAMD17-98-1-8289<br />
Report No.(s): AD-A385905; No Copyright; Avail: CASI; A03, Hardcopy; A01, Microfiche<br />
Heregulin (HRG) is a growth factor that activates erbB-2-3-4 receptors. We have generated a novel model of tumor progression<br />
from a hormone-dependent to a hormone-independent phenotype by introducing HRG into breast cancer cells. We now would<br />
like to investigate the mechanism by which HRG induces tumor progression. Our working hypothesis is that expression of HRG<br />
induces an uncontrolled mitogen-activated protein kinase (MAPK) cascade producing unbalanced growth promoting genes. The<br />
proposed studies aim to determine whether blocking MAPK activation, cells revert to become hormone-dependent <strong>and</strong> antiestrogen<br />
responsive. During the first year of funding, we maintained the timeline outlined in the statement of work: a) Generated a Ras<br />
dominant negative (N17) regulated expression vector; b) Performed transfections into a number of MCF-71HRG cells <strong>and</strong> isolated<br />
specific drug-resistant clones; c) Partially characterized these clones; <strong>and</strong> d) Initiated the construction of the MAPK mutant.<br />
The major findings of our work are that expression of N17 in MCF-7HRG cells results in reversion from an anchorage-independent<br />
to anchorage-dependent phenotype. Moreover, when analyzing the response to estradiol, MCF-7/HRG/N17 cells regained<br />
hormonal response to a level of the wild type MCF-7 cells. This data demonstrates activation of the MAPK via the HRG pathway<br />
promotes an aggressive hormone-independent phenotype.<br />
DTIC<br />
Estrogens; Hormones; Resistance; Hormone Metabolisms; Cancer<br />
<strong>2001</strong>0025764 California Univ., Los Angeles, CA USA<br />
UCLA/USC Tumor Tissue Bank Final Report, 15 Sep. 1994-14 Sep. 1999<br />
Slamon, Dennis J.; Oct. 1999; 18p; In English<br />
Contract(s)/Grant(s): DAMD17-94-J-4234<br />
Report No.(s): AD-A385906; No Copyright; Avail: CASI; A03, Hardcopy; A01, Microfiche<br />
The UCLA/USC Tissue Bank was established to provide research investigators with a ready source of human tissue samples<br />
for basic <strong>and</strong> clinical research projects directed at greater underst<strong>and</strong>ing of various aspects of human breast cancer. The bank has<br />
been successful at accruing some 2423 tissue samples to 5 of 6 subcomponent banks comprising the main bank. These samples<br />
include breast cancer specimens, premalignant <strong>and</strong> non-malignant breast tissue, normal breast tissue, normal non-breast tissue,<br />
<strong>and</strong> bone marrow <strong>and</strong> peripheral stem cells from patients with active breast cancer. Though funding under this award is now<br />
exhausted, in the coming year we still expect exp<strong>and</strong>ed utilization of the bank by a greater number of investigators as well as continued<br />
accrual to the bank.<br />
DTIC<br />
Clinical Medicine; Cancer; Tissues (Biology)<br />
<strong>2001</strong>0025765 Pennsylvania Univ., Medical Image Processing Group, Philadelphia, PA USA<br />
A Computational Approach Toward Identification of Malignant Lesions of the Human Breast: The Dynamics of Magnetic<br />
Resonance Imaging Contrast Agent Uptake Annual Report, 1 Sep. 1998-31 Aug. 1999<br />
Kaufman, Jonathan H.; Leigh, John S.; Sep. 1999; 34p; In English<br />
Contract(s)/Grant(s): DAMD17-98-1-8231<br />
Report No.(s): AD-A385911; No Copyright; Avail: CASI; A03, Hardcopy; A01, Microfiche<br />
Dynamic Gd-DTPA-2 contrast enhanced MRI images are currently used to help identify the malignancy of breast lesions.<br />
The time course of contrast agent uptake may thus be a non- invasive method for discriminating benign vs. malignant breast<br />
lesions. In this study, a computational technique called fuzzy clustering is employed to empirically categorize voxels of breast<br />
MRI images based on the time course of contrast agent enhanced image intensity. Several parameters of the clustering algorithm<br />
have been optimized including the fuzzy index <strong>and</strong> cluster membership thresholds. The clustering algorithm has been able to discriminate<br />
contrast uptake heterogeneity within breast lesions, <strong>and</strong> central vs. peripheral regions. These two features have not, on<br />
their own, discriminated malignant vs. benign lesions.<br />
DTIC<br />
Heterogeneity; Mammary Gl<strong>and</strong>s; Magnetic Resonance; Imaging Techniques; Cluster Analysis; Cancer<br />
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