NASA Scientific and Technical Aerospace Reports

esearch fellowship will reflect KCI’s conviction that elucidation of the biological basis of human cancer and the application
of results from basic research in the clinic requires knowledge and training in many disciplines including biochemistry,
pathology, molecular biology, immunology, therapeutics, pharmacology and chemistry. The goal of this training program will
be to develop within each student the approach to critical scientific thought needed to pursue independent research, stimulating
the student’s desire for a future career in breast cancer research.
DTIC
Cancer; Education; Mammary Glands; Medical Science; Summer
20040111714 California Univ., San Francisco, CA
A New Perspective on DCIS Using MRI: Correlation of Tumor and Vessel Proliferation with MR Signal Enhancement
Esserman, Laura J.; Apr. 2004; 36 pp.; In English
Contract(s)/Grant(s): DAMD17-00-1-0597
Report No.(s): AD-A425879; No Copyright; Avail: CASI; A03, Hardcopy
The purpose of our study was to determine whether MRI features could distinguish biologic characteristics of DCIS. We
identified 100 patients at USCF who had a diagnosis of DCIS and underwent MRI scanning prior to definitive surgery. 66
scans were evaluable on PACS and characterized by enhancement patterns, density of lesion, extent of breast involved,
dynamic pattern, and size. MRI enhancement characteristics were correlated with pathology characteristics (70 cases) and
immunohistochemical markers of proliferation, angiogenesis, and inflammation to assess the value of MRI as a non-invasive,
surrogate marker. 57 patients had sufficient tissue for immunohistochemistry analysis. Size, as measured by MRI and
pathology, were significantly correlated (0.001). Considering the imprecise nature of measuring the physical size of DCIS
lesions, the demonstrated correlation is remarkable, and certainly far better than mammography. We expected that markers of
angiogenesis, proliferation, and inflammation would be distinguishable by MR. However, angiogenesis (CD34) did not
correlate with any MRl characteristics, or with nuclear grade. In contrast, the inflammatory marker, CD68, strongly correlated
with all of the DCIS markers known to be associated with bad outcomes (higher progression rates), including lesion size (on
both MRl and pathology), extensive comedonecrosis, high nuclear grade, and the percent of breast involved on MRl (0.001),
and MR size (0. 01), and regional enhancement pattern. Interestingly, CD68 was also correlated with MRI density (0.001),
the measure of a lesion’s enhancement concentration developed specifically for this study. Ki67 was correlated with MR
wash-out and enhancement patterns. The patterns of MRI enhancement suggest the type of DCIS present- very small focal
masses were most likely to be ER positive, whereas regional/multi-regional had a lower ER score, higher grade, much higher
CD68 count and extensive comedonecrosis.
DTIC
Augmentation; Cancer; Correlation; Mammary Glands; Tumors
20040111716 California Univ., Berkeley, CA
How Does Nuclear Organization Maintain Normal Mammary Phenotype?
Lelievre, Sophie A.; Mar. 2004; 19 pp.; In English; Original contains color illustrations
Contract(s)/Grant(s): DAMD17-00-1-0226
Report No.(s): AD-A425883; No Copyright; Avail: CASI; A03, Hardcopy
Degradation of the basement membrane (BM) surrounding epithelial units (acini) is associated with tumor progression.
It is crucial to understand the molecular mechanisms that underlie the maintenance of an intact BM in order to develop
anti-cancer strategies. Using non-neoplastic human breast epithelial S1 cells that differentiate into acini in the presence of
extracellular matrix, we have shown a link between the nuclear organization of the protein NuMA, via its C-terminus, and the
maintenance of acinar differentiation, notably BM integrity. We have identified a sequence that shares similarities with the
histone promoter control 2 (HPC2) protein in the distal portion of the C-terminus of NuMA (NuMA- CTDP). Expression of
this sequence in 51 cells prevented acinar differentiation and formation of the BM, and induced a dramatic reorganization of
chromatin structure. Fractionation experiments showed that NuMA interacts with the chromatin compartment and suggested
that NuMA might be associated with multi-protein complexes. Further sequence analysis of NuMA- CTDP revealed that this
region may be restricted to chordates and may adopt a structure possessing organization and signaling properties. Further
understanding of the involvement of NuMA in the regulation of chromatin structure is critical to establish whether this protein
could become a target for differentiation strategies.
DTIC
Cancer; Mammary Glands; Proteins
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