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Search Results: 1 - 10 of 158182 matches for " Adrian V Lee "
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Location, location, location: regulation of breast cancer progression by the microenvironment
Adrian V Lee
Breast Cancer Research , 2004, DOI: 10.1186/bcr957
Abstract: Global gene expression patterns have revealed distinct subtypes of breast cancer, and can predict metastasis and survival. The development of gene array technology has quickly evolved to allow analysis of very small specimens derived by laser capture microdissection or cell fractionation. This has given an invaluable view of the gene expression changes within specific cell types during breast cancer progression. In this regard, Allinen and colleagues [1] performed an exhaustive analysis of gene expression changes using serial analysis of gene expression (SAGE) on specific cell types (luminal epithelial, myoepithelial, endothelial, leukocytes, and myofibroblasts) during breast cancer progression. While luminal epithelial cells showed gene abnormalities (loss of heterozygosity) and expression changes during progression, the most dramatic changes in gene expression occurred in the myoepithelial cells. This was despite the fact that the myoepithelial cells showed no genomic alterations. Interestingly, the gene expression changes in the myoepithelial cells often included secreted proteins and receptors, suggesting a paracrine regulation of breast epithelial cells. To support this, Allinen and colleagues showed that chemokines that are highly upregulated in myoepithelial cells (CXCL12 and CXCL14) can bind breast tumor epithelial cells and regulate their proliferation, migration and invasion. Inhibition of CXCR4, the receptor for CXCL12, has been shown to prevent breast cancer metastasis [2], providing the opportunity for therapeutic targeting of the microenvironment with potentially less chance of acquired resistance.Mammary gland biologists have long believed in the usefulness of their models for understanding breast cancer progression, but new, sophisticated genetic and molecular approaches are really bringing these models to the forefront.Integrin receptors transmit signals from the microenvironment and extracellular matrix to breast epithelial cells. They have long be
26th Annual San Antonio Breast Cancer Symposium, San Antonio, Texas, USA, 3–6 December 2003: update on preclinical and translational research
Adrian V Lee, Gary Chamness, Steffi Oesterreich
Breast Cancer Research , 2004, DOI: 10.1186/bcr758
Abstract: The 26th Annual San Antonio Breast Cancer Symposium was held in San Antonio, Texas on 3–6 December 2003. Over the past 26 years this meeting has evolved into the largest conference in the world devoted solely to breast cancer research. This year there were more than 700 abstract presentations, from 6000 attendees representing 80 countries. This not only included physicians and scientists who presented the newest information on prevention, diagnosis, and treatment of breast cancer, but also included breast cancer patient advocates. In the spirit of the late William L McGuire, who co-founded this symposium with Charles A Coltman Jr in 1978, cellular and molecular biology with translational potential was presented, and the highlights will now be discussed.The meeting was opened by a plenary lecture on stem cells in normal breast development and breast cancer by Max Wicha (University of Michigan, Ann Arbor, Michigan, USA). Wicha pointed out that many features of stem cells are also shared with breast cancer cells, including the ability to self renew and differentiate, telomerase activity, resistance to damaging agents, and anchorage-independent growth and survival (abstract P1 [1]).Wicha has developed a new in vitro culture system allowing the propagation of putative stem cells from normal breast tissue [2]. In this situation, cells grow in perfect spheroids, termed mammospheres, and show the two classic features of stem cells: the ability both to self renew and to differentiate. Microarray analysis of these cells showed expression of many genes that are similar to those expressed in hemopoetic cells, neuronal cells, and embryonic stem cells. Importantly, when overexpressed in the mammary gland, many of these genes result in tumorigenesis.Wicha went on to show that breast cancers contain putative cancer stem cells that can be selected by specific cell surface markers such as CD44 and CD24. Blockade of the Notch 4 ligand, which is highly expressed in normal stem cells, c
Articles selected in January 2005
Adrian Lee
Breast Cancer Research , 2005, DOI: 10.1186/bcr1008
Articles selected in November 2004
Adrian Lee
Breast Cancer Research , 2004, DOI: 10.1186/bcr986
Hand hygiene: two fundamental strategies for improving compliance
Adrian YS Lee
International Journal of Students' Research , 2011, DOI: 10.5549/ijsr.1.2.67
A moderate elevation of circulating levels of IGF-I does not alter ErbB2 induced mammary tumorigenesis
Robert K Dearth, Isere Kuiatse, Yu-Fen Wang, Lan Liao, Susan G Hilsenbeck, Powel H Brown, Jianming Xu, Adrian V Lee
BMC Cancer , 2011, DOI: 10.1186/1471-2407-11-377
Abstract: We crossed heterozygous TTR-IGF-I mice with heterozygous MMTV-ErbB2 mice to generate 4 different genotypes: TTR-IGF-I/MMTV-ErbB2 (bigenic), TTR-IGF-I only, MMTV-ErbB2 only, and wild type (wt). Virgin females were palpated twice a week and harvested when tumors reached 1000 mm3. For study of normal development, blood and tissue were harvested at 4, 6 and 9 weeks of age in TTR-IGF-I and wt mice.TTR-IGF-I and TTR-IGF-I/ErbB2 bigenic mice showed a moderate 35% increase in circulating total IGF-I compared to ErbB2 and wt control mice. Elevation of circulating IGF-I had no effect upon pubertal mammary gland development. The transgenic increase in IGF-I alone wasn't sufficient to initiate mammary tumorigenesis. Elevated circulating IGF-I had no effect upon ErbB2-induced mammary tumorigenesis or metastasis, with median time to tumor formation being 30 wks and 33 wks in TTR-IGF-I/ErbB2 bigenic and ErbB2 mice respectively (p = 0.65). Levels of IGF-I in lysates from ErbB2/TTR-IGF-I tumors compared to ErbB2 was elevated in a similar manner to the circulating IGF-I, however, there was no effect on the rate of tumor growth (p = 0.23). There were no morphological differences in tumor type (solid adenocarcinomas) between bigenic and ErbB2 mammary glands.Using the first transgenic animal model to elevate circulating levels of IGF-I to those comparable to women at increased risk of breast cancer, we showed that moderately high levels of systemic IGF-I have no effect on pubertal mammary gland development, initiating mammary tumorigenesis or promoting ErbB2 driven mammary carcinogenesis. Our work suggests that ErbB2-induced mammary tumorigenesis is independent of the normal variation in circulating levels of IGF-I.IGF-I has the characteristics of both a circulating hormone and a tissue growth factor. While numerous studies have focused on the autocrine and/or paracrine ability of IGF-I to regulate mammary gland development and tumorigenesis [1], only a few have focused on the role of c
Scaffold attachment factor B1 (SAFB1) heterozygosity does not influence Wnt-1 or DMBA-induced tumorigenesis
Benny Kaipparettu, Klaudia M Dobrzycka, Ora Britton, Adrian V Lee, Alan J Herron, Yi Li, Michael T Lewis, Daniel Medina, Steffi Oesterreich
Molecular Cancer , 2009, DOI: 10.1186/1476-4598-8-15
Abstract: We crossed female SAFB1+/- (C57B6/129) mice with male MMTV-Wnt-1 (C57B6/SJL) mice to obtain SAFB1+/+/Wnt-1, SAFB1+/-/Wnt-1, and SAFB1+/- mice. For the chemical induced tumorigenesis study we treated 8 weeks old SAFB1+/- and SAFB+/+ BALB/c mice with 1 mg DMBA once per week for 6 weeks. Animals were monitored for tumor incidence and tumor growth. Tumors were characterized by performing H&E, and by staining for markers of proliferation and apoptosis.We did not detect significant differences in tumor incidence and growth between SAFB1+/+/Wnt-1 and SAFB1+/-/Wnt-1 mice, and between DMBA-treated SAFB1+/+ and SAFB1+/-mice. Histological evaluation of tumors showed that SAFB1 heterozygosity did not lead to changes in proliferation or apoptosis. There were, however, significant differences in the distribution of tumor histologies with an increase in papillary and cribriform tumors, and a decrease in squamous tumors in the SAFB1+/-/Wnt-1 compared to the SAFB1+/+/Wnt-1 tumors. Of note, DMBA treatment resulted in shortened survival of SAFB1+/- mice compared to their wildtype littermates, however this trend did not reach statistical significance.Our data show that SAFB1 heterozygosity does not influence Wnt-1 or DMBA-induced mammary tumorigenesis.Scaffold Attachment Factor B1 (SAFB1) is a multifunctional protein that is involved in RNA processing, transcriptional regulation, and stress response [1]. SAFB1 has previously been implicated in breast tumorigenesis. SAFB1 functions as an estrogen receptor α (ERα) corepressor [2], and its overexpression in cultured cells leads to growth inhibition. Importantly, SAFB1 mutations have been identified in microdissected breast tumors but not in the normal adjacent tissue, and SAFB1's chromosomal locus displays extremely high loss of heterozygocity LOH (78%) in invasive breast cancer [3]. There is no significant different in LOH frequencies between ER-positive and ER-negative tumors, and other in vitro observations [4] suggest that SAFB1 could
Stoichiometric estimates of the biochemical conversion efficiencies in tsetse metabolism
Adrian V Custer
BMC Ecology , 2005, DOI: 10.1186/1472-6785-5-6
Abstract: This paper presents estimates of the net amounts of ATP, fat, or protein obtained by tsetse from a starting milligram of blood, and provides estimates of the net amounts of ATP formed from the catabolism of a milligram of fat along two separate pathways, one used for resting metabolism and one for flight. These estimates are derived from stoichiometric calculations constructed based on a detailed quantification of the composition of food and body tissue and on a description of the major metabolic pathways in tsetse simplified to single reaction sequences between substrates and products. The estimates include the expected amounts of uric acid formed, oxygen required, and carbon dioxide released during each conversion. The calculated estimates of uric acid egestion and of oxygen use compare favorably to published experimental measurements.This biochemical analysis provides reasonable first estimates of the conversion efficiencies for the major pathways used by tsetse metabolism. These results now enable a deeper analysis of tsetse ecology based on the construction of a dynamic mass-energy budget for tsetse and their populations.The dynamics of mass and energy flows in tsetse (Glossina Wiedemann), the time-varying rates of biomass ingestion and use, influence most aspects of the ecology of these flies including the nutrition and growth of individuals, the intrinsic growth rate of tsetse populations, and the transmission dynamics of the tsetse vectored trypanosomiases. A particularly effective approach to the examination of these dynamics involves the assembly and evaluation of a dynamic mass-energy budget [1-3] constructed specifically for tsetse. Such a budget could capture the essence of the time varying flows of biomass and energy in tsetse, could explain these dynamics mechanistically based on the internal physiology of the flies, and could form the core of a physiologically based model of tsetse population dynamics [4-6]. The budget and population model could, in
Faraday instability on viscous ferrofluids in a horizontal magnetic field: Oblique rolls of arbitrary orientation
V. V. Mekhonoshin,Adrian Lange
Physics , 2002, DOI: 10.1103/PhysRevE.65.061509
Abstract: A linear stability analysis of the free surface of a horizontally unbounded ferrofluid layer of arbitrary depth subjected to vertical vibrations and a horizontal magnetic field is performed. A nonmonotonic dependence of the stability threshold on the magnetic field is found at high frequencies of the vibrations. The reasons of the decrease of the critical acceleration amplitude caused by a horizontal magnetic field are discussed. It is revealed that the magnetic field can be used to select the first unstable pattern of Faraday waves. In particular, a rhombic pattern as a superposition of two different oblique rolls can occur. A scaling law is presented which maps all data into one graph for the tested range of viscosities, frequencies, magnetic fields and layer thicknesses.
Chain-induced effects in the Faraday instability on ferrofluids in a horizontal magnetic field
V. V. Mekhonoshin,Adrian Lange
Physics , 2004, DOI: 10.1063/1.1649757
Abstract: The linear stability analysis of the Faraday instability on a viscous ferrofluid in a horizontal magnetic field is performed. Strong dipole-dipole interactions lead to the formation of chains elongated in the field direction. The formation of chains results in a qualitative new behaviour of the ferrofluid. This new behaviour is characterized by a neutral stability curve similar to that observed earlier for Maxwell viscoelastic liquids and causes a significant weakening of the energy dissipation at high frequencies. In the case of a ferrofluid with chains in a horizontal magnetic field, the effective viscosity is anisotropic and depends on the field strength as well as on the wave frequency.
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