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Scientific and Technical Aerospace Reports Volume 39 April 6, 2001

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Prior to 1994, measurement of tumor pH was limited to microelectrodes, which measure the interstitial/extracellular pH<br />

(pHe), <strong>and</strong> (31)P MRS of inorganic phosphate, which measured the intracellular pH (pHe). In 1994, we developed a method to<br />

simultaneously measure the intra <strong>and</strong> extracellular pH of tumors, using exogenous 3-amino propyl phosphonate (3-APP) <strong>and</strong> inorganic<br />

phosphate (Pi) (Gillies et al., 1994, Am J Physiol 267, C195-C203). However, this method is limited to measuring average<br />

tumor pHe, <strong>and</strong> was not capable of reporting the pH range or localized values. MR-based pH measurement techniques have been<br />

improved in two ways. First, the data obtained from (31)P MRS of 3-APP have been more thoroughly analyzed to yield transtumoral<br />

pH ranges. Second, an alternative pH-sensitive marker has been developed to allow pH in mapping using multivoxel<br />

(1)H-MRS.<br />

DTIC<br />

Mammary Gl<strong>and</strong>s; Cancer; Amines<br />

<strong>2001</strong>0025308 Duke Univ., Medical Center, Durham, NC USA<br />

A Pilot Study to Explore Linkages Among Isomers of Organochlorines, Promutagenic DNA Lesions <strong>and</strong> Breast Cancer<br />

Using Sensitive Techniques Final Report, 1 Jul. 1996-31 Dec. 1999<br />

Lo, Joseph; Jan. 2000; 25p; In English<br />

Contract(s)/Grant(s): DAMD17-96-1-6145<br />

Report No.(s): AD-A385883; No Copyright; Avail: CASI; A03, Hardcopy; A01, Microfiche<br />

The purpose of this grant was to construct an artificial neural network (ANN) to assist radiologists in differentiating benign<br />

from malignant solid lesions in ultrasound (U.S.) breast imaging. A data set of patient cases was collected, consisting of 192<br />

biopsy-proven breast lesions for which radiologists provided descriptive terms to characterize the U.S. appearance of the lesions.<br />

An ANN model was developed to predict probably benign lesions based upon those descriptors <strong>and</strong> the patient age. The model<br />

was potentially able to maintain 100% sensitivity of cancer detection, while improving the radiologists’ specificity from 0% to<br />

35% (42 out of 121 benign biopsies obviated). This corresponded to improving the PPV of the radiologists from 37% to 47%.<br />

Moreover, we also identified that the mass margin <strong>and</strong> patient age were the two most important input features for this model, <strong>and</strong><br />

that highly simplified models based on those two features alone could still perform as well as the more complicated models using<br />

all available information. Predictive models such as these can provide physicians <strong>and</strong> patients with accurate information for managing<br />

suspicious breast lesions without the invasiveness of biopsy procedures.<br />

DTIC<br />

Cancer; Imaging Techniques; Computer Assisted Instruction<br />

<strong>2001</strong>0025309 Virginia Univ., Charlottesville, VA USA<br />

Involvement of the Tyrosine Phosphatase SHP-1 in the Development of Breast Cancer Annual Report, 1 Oct. 1998-30 Sep.<br />

1999<br />

Lorenz, Ulrike; Oct. 1999; 11p; In English<br />

Contract(s)/Grant(s): DAMD17-98-1-8347<br />

Report No.(s): AD-A385886; No Copyright; Avail: CASI; A03, Hardcopy; A01, Microfiche<br />

The purpose of this research was to test the working hypothesis that SHP-1 is essential for controlling growth <strong>and</strong> differentiation<br />

of mammary epithelial cells <strong>and</strong> that dysregulation of SHP-1 contributes to the development of breast cancer. Scope: to<br />

biochemically <strong>and</strong> functionally characterize SHP-1 in human breast cancer cell lines <strong>and</strong> to define the biological function of<br />

SHP-1 in normal epithelial cells. Major Findings: SHP-1 associates with the EGFR in an EGF stimulation-dependent manner. to<br />

further characterize the function of SHP- 1, we have generated retroviruses encoding wild type <strong>and</strong> mutant forms of SHP- 1<br />

together with GFP. Infection of cell lines with these viruses will enable us to target a high percentage of the cell population <strong>and</strong><br />

to identify infected cells. We have also generated a transgenic mouse encoding SHP-1 under the control of its hematopoietic promoter.<br />

Crossing this mouse in the motheaten background should allow us to study SHP- 1-deficient epithelial cells in an otherwise<br />

”normal” mouse. Significance: From our data, we are starting to underst<strong>and</strong> SHP-1’s role in epithelial cells. Moreover by using<br />

the reagents we generated, we expect to deepen our knowledge of SHP-1’s role in epithelial cells <strong>and</strong> to learn how a dysregulated<br />

SHP-1 is potentially involved in the onset/progression of breast cancer.<br />

DTIC<br />

Proteins; Tyrosine; Hematopoietic System; Cells (Biology); Cancer<br />

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