NASA Scientific and Technical Aerospace Reports

Some cellular factors that contribute to making a cell resistant to chemotherapy drugs have been identified, though many still
remain to be discovered. These cellular factors or proteins involved in drug resistance can be measured using sensitive
analytical techniques. A. major goal of the research proposed in this study is to analyze these proteins from ovarian cancer
cell lines that are known to be either sensitive or resistant to the chemotherapeutic drug cisplatin, a first line treatment for
ovarian cancer. We will determine if there is a specific protein ‘f ingerprint’ that is indicative of either sensitivity or resistance
to cisplatin. Once the useful factors that influence drug resistance are identified in cell lines and verified using tumor biopsies,
we anticipate that this information could then be used to help predict whether a specific tumor will respond to a specific
treatment. To date, the sensitivity of a specific ovarian carcinoma to a specific treatment can only be assessed by administration
of the treatment and then observ%ng the outcome. Knowing the factors that contribute to a cancer being sensitive or resistant
and having the methods to determine if these factors are present or absent in a given tumor are the goals of this proposal. This
information could then be used in the clinical assessment to determine the best course of treatment for a specific cancer.
DTIC
Cancer; Ovaries; Proteome
20040111569 Thomas Jefferson Univ., Philadelphia, PA
Ultrasound Activated Contrast Imaging for Prostate Cancer Detection
Forsberg, Flemming; Mar. 2004; 15 pp.; In English
Contract(s)/Grant(s): DAMD17-03-1-0119
Report No.(s): AD-A425621; No Copyright; Avail: CASI; A03, Hardcopy
The diagnosis of prostate cancer is currently based on elevated PSA levels or abnormal digital rectal examination
confirmed with needle biopsy of the prostate. However, for most screening populations, the frequency of positive biopsy
findings is as low as 25%. Therefore, an accurate, noninvasive diagnostic imaging examination of the prostate is needed as
a replacement of or an alternative to biopsy. Hence, the current project proposes to develop a novel ultrasound contrast
imaging technique (called EEI) for better visualization of the microvessels, which are characteristic of the neovasculature
associated with prostate cancer. To date, a pulse-echo system was built to perform in vitro EEI measurements and initial
experiments were conducted with 4 contrast agents. Up to 10 dB of enhancement was measured at 37c with Optison. Higher
frequency detection pulses are currently being evaluated. A new zero-thickness interface model was developed to describe the
encapsulation of microbubble contrast agents. While the model was fitted based on linear measurements, the model predictions
were compared to measured nonlinear subharmonic signals. The current model shows a much better match with the
experimental data at frequencies of 3.0 and 4.4MHz than other models. The dual pulse imaging mode associated with EEI is
currently being modeled.
DTIC
Cancer; Data Recording; Diagnosis; Digital Systems; Imaging Techniques; In Vitro Methods and Tests; Physical
Examinations; Prostate Gland; Ultrasonics
20040111573 Texas Univ., Houston, TX
Functional Analysis of C-CAM1 Tumor Suppressor Gene by Targeted Gene Deletion
Lin, Sue-Hwa; Jan. 2004; 23 pp.; In English; Original contains color illustrations
Contract(s)/Grant(s): DAMD17-00-1-0031
Report No.(s): AD-A425625; No Copyright; Avail: CASI; A03, Hardcopy
CEACAM1 is a cell adhesion molecule. Alternative splicing of the Ceacam1 gene generated two isoforms of CEACAM1,
i.e. CEACAM1-L (long form) and CEACAM1-S (short form). We have shown that CEACAM1-L plays critical roles in
prostate cancer progression. We propose to determine the function of CEACAM1 in prostate development, prostate
homeostasis and prostate tumorigenesis by using gene targeting technologies. Specifically, we plan to generate mice with a
targeted deletion of the CEACAM1 cytoplasmic domain. We have constructed a Ceacam1 targeting vector in which exons 7-9
of Ceacam1 gene was flanked by loxP sites for the generation of conditional knockout of the Ceacam1 gene. Embryonic stem
cell clones containing the recombinant gene allele were established and injected into blastocysts for germ line transmission
of the targeting construct; We have succeeded in producing mice harboring the conditional Ceacam1 knockout allele. In this
extended period, we generated mice with homozygote conditional Ceacam1 allele and characterized the expression of
CEACAM1 protein. In addition, we have crossed the homozygote conditional Ceacam1 mice with transgenic mice containing
probasin-driven cre to generate mice with prostate-specific deletion of Ceacam1 gene. Initial analysis of 3 month old mouse
prostates showed that deletion of Ceacam1-L in the mouse prostates led to epithelial hyperplasia.
DTIC
Cancer; Deletion; Functional Analysis; Genes; Prostate Gland; Stem Cells; Tumor Suppressor Genes
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