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Sent on Sunday, 2008 Nov 02.
Search breast cancer
Click on the following url to view complete results in pubmed. (Results may change over time.)
http://www.ncbi.nlm.nih.gov/entrez/cubby.fcgi?call=0JYo4bxgiqFTiCxz9_PJ16_GiRhguvew7R4LTWkn3moHsbPAwBqTKCXmuVfItbl&WebCubbyUser=089oOE1Za1Dbgf99SPU-PCY8%40990F164C90DB9481_0019SID
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==================== Entrez pubmed Results ======================
Items 1 - 5 of 149
1: Clin Exp Metastasis. 2008 Oct 31; [Epub ahead of print]
In vitro binding evaluation of (177)Lu-AMBA, a novel (177)Lu-labeled GRP-R
agonist for systemic radiotherapy in human tissues.
Thomas R, Chen J, Roudier MM, Vessella RL, Lantry LE, Nunn AD.
Discovery Biology, Ernst Felder Laboratories, Bracco Research USA, Princeton,
NJ, 08540, USA, Regi.Thomas@BRU.Bracco.com.
Members of the gastrin-releasing peptide (GRP) family and its analogs bombesin
(BBN) have been implicated in the biology of several human cancers including
prostate, breast, colon and lung. To date, three mammalian GRP/BBN receptor
subtypes have been cloned and characterized: the neuromedin B receptor (NMBR),
the GRP receptor (GRPR) and the BBN-receptor subtype 3 (BB(3)). The fourth BBN
receptor subtype, BB(4), has only been identified in amphibian and at present no
mammalian equivalent of this receptor has been described. GRPR analogs have been
used as carriers to deliver drugs, radionuclides and cytotoxins to target
various cancer types that are GRPR positive. We investigated the in vitro
binding properties of (177)Lu-AMBA, a novel radiolabelled BBN analog currently
undergoing clinical trial as systemic radiotherapy for hormone refractory
prostate cancer (HRPC) patients. Pharmacological analyses of the (177)Lu-AMBA
was determined using in vitro binding studies using membrane target system
containing specific receptor subtypes. We investigated the distribution of
binding sites for (177)Lu-AMBA by receptor autoradiography on human neoplastic
and non-neoplastic tissues. Pharmacological characterizations of (177)Lu-AMBA
shows, high affinity towards NMB and GRP receptors, while little or no affinity
towards BB(3) receptor. Among the 40 different types of non-neoplastic tissues
tested seven of them showed limited but specific binding of (177)Lu-AMBA.
Fourteen of 17 primary prostate cancers, six of 13 primary breast cancers
expressed binding sites for (177)Lu-AMBA. Furthermore, no apparent differences
in (177)Lu-AMBA-binding sites expression were observed between matched pairs
(primary vs. secondary) of prostate and breast cancer tissues. These data
represent the molecular basis for clinical applications of (177)Lu-AMBA for
diagnosis and treatment of GRP-R and NMB-R positive tumors.
PMID: 18975117 [PubMed - as supplied by publisher]
2: J Biol Inorg Chem. 2008 Oct 31; [Epub ahead of print]
Targeted Herceptin-dextran iron oxide nanoparticles for noninvasive imaging of
HER2/neu receptors using MRI.
Chen TJ, Cheng TH, Chen CY, Hsu SC, Cheng TL, Liu GC, Wang YM.
Department of Biological Science and Technology, National Chiao Tung University,
75 Bo-Ai Street, Hsinchu, 300, Taiwan.
A novel magnetic resonance imaging (MRI) contrast agent containing Herceptin is
reported. The surfaces of superparamagnetic iron oxide nanoparticles were
modified with dextran and conjugated with Herceptin (Herceptin-nanoparticles) to
improve their dispersion, magnetization, and targeting of the specific receptors
on cells. From analytical results, we found that Herceptin-nanoparticles were
well dispersed in solutions of various pH range, and had no hysteresis, high
saturation magnetization (80 emu/g), and low cytotoxicity to a variety of cells.
Notably, the magnetic resonance enhancements for the different breast cancer
cell lines (BT-474, SKBR-3, MDA-MB-231, and MCF-7) are proportional to the
HER2/neu expression level in vitro. When Herceptin-nanoparticles were
administered to mice bearing breast tumor allograft by intravenous injection,
the tumor site was detected in T (2)-weighted magnetic resonance images as a 45%
enhancement drop, indicating a high level of accumulation of the contrast agent
within the tumor sites. Therefore, targeting of cancer cells was observed by in
vitro and in vivo MRI studies using Herceptin-nanoparticles contrast agent. In
addition, Herceptin-nanoparticles enhancing the magnetic resonance signal
intensity were sufficient to detect the cell lines with a low level of HER2/neu
expression.
PMID: 18975017 [PubMed - as supplied by publisher]
3: Mol Cancer Ther. 2008 Oct 30; [Epub ahead of print]
Carprofen induction of p75NTR-dependent apoptosis via the p38 mitogen-activated
protein kinase pathway in prostate cancer cells.
Khwaja FS, Quann EJ, Pattabiraman N, Wynne S, Djakiew D.
Department of Biochemistry and Molecular & Cellular Biology and Vincent T.
Lombardi Comprehensive Cancer Center, Georgetown University Medical Center,
Washington, District of Columbia; and Immunology Program, Memorial Sloan
Kettering Cancer Center, New York, New York.
The p75 neurotrophin receptor (p75(NTR)) functions as a tumor suppressor in
prostate epithelial cells, where its expression declines with progression to
malignant cancer. Previously, we showed that treatment with R-flurbiprofen or
ibuprofen induced p75(NTR) expression in several prostate cancer cell lines
leading to p75(NTR)-mediated decreased survival. Using the 2-phenyl propionic
acid moiety of these profens as a pharmacophore, we screened an in silico
database of 30 million compounds and identified carprofen as having an order of
magnitude greater activity for induction of p75(NTR) levels and inhibition of
cell survival. Prostate (PC-3 and DU-145) and bladder (T24) cancer cells were
more sensitive to carprofen induction of p75(NTR)-associated loss of survival
than breast (MCF-7) and fibroblast (3T3) cells. Transfection of prostate cell
lines with a dominant-negative form of p75(NTR) before carprofen treatment
partially rescued cell survival, showing a cause-and-effect relationship between
carprofen induction of p75(NTR) levels and inhibition of survival. Carprofen
induced apoptotic nuclear fragmentation in prostate but not in MCF-7 and 3T3
cells. Furthermore, small interfering RNA knockdown of the p38 mitogen-activated
protein kinase (MAPK) protein prevented induction of p75(NTR) by carprofen in
both prostate cell lines. Carprofen treatment induced phosphorylation of p38
MAPK as early as within 1 min. Expression of a dominant-negative form of MK2,
the kinase downstream of p38 MAPK frequently associated with signaling cascades
leading to apoptosis, prevented carprofen induction of the p75(NTR) protein.
Collectively, we identify carprofen as a highly potent profen capable of
inducing p75(NTR)-dependent apoptosis via the p38 MAPK pathway in prostate
cancer cells. [Mol Cancer Ther 2008;7(11):3539-45].
PMID: 18974393 [PubMed - as supplied by publisher]
4: Mol Cancer Ther. 2008 Oct 30; [Epub ahead of print]
Quantitative live imaging of cancer and normal cells treated with Kinesin-5
inhibitors indicates significant differences in phenotypic responses and cell
fate.
Orth JD, Tang Y, Shi J, Loy CT, Amendt C, Wilm C, Zenke FT, Mitchison TJ.
Department of Systems Biology, Harvard Medical School, Boston, Massachusetts;
Prince of Wales Medical Research Institute, Randwick, New South Wales,
Australia; and Merck Serono, Darmstadt, Germany.
Kinesin-5 inhibitors (K5I) are promising antimitotic cancer drug candidates.
They cause prolonged mitotic arrest and death of cancer cells, but their full
range of phenotypic effects in different cell types has been unclear. Using
time-lapse microscopy of cancer and normal cell lines, we find that a novel K5I
causes several different cancer and noncancer cell types to undergo prolonged
arrest in monopolar mitosis. Subsequent events, however, differed greatly
between cell types. Normal diploid cells mostly slipped from mitosis and
arrested in tetraploid G1, with little cell death. Several cancer cell lines
died either during mitotic arrest or following slippage. Contrary to prevailing
views, mitotic slippage was not required for death, and the duration of mitotic
arrest correlated poorly with the probability of death in most cell lines. We
also assayed drug reversibility and long-term responses after transient drug
exposure in MCF7 breast cancer cells. Although many cells divided after drug
washout during mitosis, this treatment resulted in lower survival compared with
washout after spontaneous slippage likely due to chromosome segregation errors
in the cells that divided. Our analysis shows that K5Is cause cancer-selective
cell killing, provides important kinetic information for understanding clinical
responses, and elucidates mechanisms of drug sensitivity versus resistance at
the level of phenotype. [Mol Cancer Ther 2008;7(11):3480-9].
PMID: 18974392 [PubMed - as supplied by publisher]
5: Cancer Res. 2008 Nov 1;68(21):9087-95.
Fibroblasts isolated from common sites of breast cancer metastasis enhance
cancer cell growth rates and invasiveness in an interleukin-6-dependent manner.
Studebaker AW, Storci G, Werbeck JL, Sansone P, Sasser AK, Tavolari S, Huang T,
Chan MW, Marini FC, Rosol TJ, Bonafe M, Hall BM.
Center for Childhood Cancer, Children's Research Institute.
Common sites of breast cancer metastasis include the lung, liver, and bone, and
of these secondary metastatic sites, estrogen receptor alpha (ERalpha)-positive
breast cancer often favors bone. Within secondary organs, cancer cells would
predictably encounter tissue-specific fibroblasts or their soluble factors, yet
our understanding of how tissue-specific fibroblasts directly affect cancer cell
growth rates and survival remains largely unknown. Therefore, we tested the
hypothesis that mesenchymal fibroblasts isolated from common sites of breast
cancer metastasis provide a more favorable microenvironment with respect to
tumor growth rates. We found a direct correlation between the ability of breast,
lung, and bone fibroblasts to enhance ERalpha-positive breast cancer cell growth
and the level of soluble interleukin-6 (IL-6) produced by each organ-specific
fibroblast, and fibroblast-mediated growth enhancement was inhibited by the
removal or inhibition of IL-6. Interestingly, mice coinjected with MCF-7 breast
tumor cells and senescent skin fibroblasts, which secrete IL-6, developed
tumors, whereas mice coinjected with presenescent skin fibroblasts that produce
little to no IL-6 failed to form xenograft tumors. We subsequently determined
that IL-6 promoted growth and invasion of breast cancer cells through signal
transducer and activator of transcription 3-dependent up-regulation of Notch-3,
Jagged-1, and carbonic anhydrase IX. These data suggest that tissue-specific
fibroblasts and the factors they produce can promote breast cancer disease
progression and may represent attractive targets for development of new
therapeutics. [Cancer Res 2008;68(21):9087-95].
PMID: 18974155 [PubMed - in process]