Gloria Chepko | Georgetown University (original) (raw)

Papers by Gloria Chepko

In studying the relationship between risk factors and breast cancer, the growth patterns of fat p... more In studying the relationship between risk factors and breast cancer, the growth patterns of fat pads and glandular tissues are considered as important biomarkers. The aim of this study is to measure the growth pattern statistics of rat mammary pads and glandular tissues with magnetic resonance (MR) time sequence images. In this paper, we proposed methods containing sequential steps to extract and analyze imaging biomarkers of rat mammary pad and glandular tissues. Firstly, to accurately segment out pads in MR images with noisy bias filed, we proposed a level set method combining local binary fitting (LBF) and geodesic active contour (GAC). The salient glandular tissue regions within the fat pads are further extracted by a scale-space analysis procedure. Then, the volume data of a single rat at different time points are aligned through profile correlation analysis. Finally, the growth rates are calculated and compared to show the changing patterns of fat pads and glandular tissues wi...

2008 19th International Conference on Pattern Recognition, Dec 1, 2008

Tissue and Cell, Apr 30, 2003

Biochimica et Biophysica Acta (BBA) - Lipids and Lipid Metabolism, 1983

The rapid degradation of phosphatidylinositol in lens epithelia is accompanied by comparably rapi... more The rapid degradation of phosphatidylinositol in lens epithelia is accompanied by comparably rapid synthesis. During this metabolic turnover only the phosphorylinositol portion of the molecule is renewed, as expected if hydrolysis occurs by the action of a phospholipase C, such as phosphatidylinositol phosphodiesterase. Thus, these data suggest that agents which produce in vitro differentiation of embryonic chicken lens epithelial cells into lens fibers lead to a reduction in either the amount or the activity of phospholipase C.

The polarization state of the light transmitting through a specimen can provide useful informatio... more The polarization state of the light transmitting through a specimen can provide useful information concerning the optical property of the sample. We present a polarization imaging device that measures the Stokes components of the trans-illuminant light. Particularly, we develop an image analysis algorithm using texture analysis and support vector machine for tissue classification. The experiment has been conducted using rat breast tissue in health and with cancer. It is demonstrated that the Stokes images can improve the classification performance of the algorithm. With the incorporation of the multi-polarization images, it is shown that the diagnosis accuracy can be further improved over that using intensity image only.

Breast Cancer Online, 2005

At least four cell types in mouse mammary epithelium, three in human, and three in cow are now kn... more At least four cell types in mouse mammary epithelium, three in human, and three in cow are now known to be proliferation competent. Some evidence indicates that pregnancy may confer proliferative competency on a new cell type. These cells are widely seen as stem and progenitor cells that maintain the epithelium and produce lactational units during pregnancy. Evolutionarily conserved developmental signaling pathways active in germinal and neuronal stem cell proliferation and differentiation in drosophila and mammalian development are implicated in mammary tumorigenesis. In adult tissues this signaling is retained, is regulated by stem cell niches and operates to create new tissue and maintain tissue form and integrity. Disruption of this signaling may abrogate maintenance of the stem cell niche and lead to preneoplastic conditions.

Protoplasma, Jan 1, 1979

Chloroplasts and mitochondria ofChlamydomonas were examined by electron microscopy to determine i... more Chloroplasts and mitochondria ofChlamydomonas were examined by electron microscopy to determine if cytoplasmic ribosomes were associated with the envelopes of these organelles. Cells were treated with cycloheximide to prevent polypeptide chain completion, and resultant dissociation of envelope-ribosome associations. No extensive association of cytoplasm ribosomes with envelopes of chloroplasts, or mitochondria was detected in intact cells or in damaged cells in which cytoplasm was partly removed. Our results indicate that association of cytoplasm ribosomes with envelopes of chloroplasts or mitochondria is not an essential requirement for transport of polypeptides from cytoplasm to organelle.

Tissue & Cell, Jan 1, 2005

Genes associated with proliferation are active in stem and progenitor cells, and their over-expre... more Genes associated with proliferation are active in stem and progenitor cells, and their over-expression can promote cancer. Two such genes, c-Myc and TGFα, promote morphologically dissimilar mammary tumors in transgenic mice. We investigated whether their over-expression affects population size and cell cycle activity in stem and other cell populations in non-neoplastic mammary epithelia. Results indicated that both cell population and cell cycle regulation are cell type- and microenvironment-specific. To create a tool for identifying and categorizing the five cellular phenotypes by light microscopy, we adapted previously established ultrastructural criteria. Using nulliparous MMTV-c-myc or MT-tgfα mice, we determined and compared the relative sizes the putative stem, progenitor and differentiated cell populations. PCNA staining was used to compare the portion of each cell population in the cell cycle. Cell population sizes were analyzed relative to: (1) their location in ducts versus lobules (microenvironment), (2) genotype, and (3) cell type. Population sizes differed significantly by genotype, depending on microenvironment (p = 0.0008), by genotype, depending on cell type (p < 0.0001), and by microenvironment, depending on cell type (p = 0.03). The number of cycling cells was also affected by all three factors, confirming that the interplay of cell type, gene expression and three-dimensional organization are very important in tissue morphogenesis and function. We describe a structure in mammary epithelium consistent with that of a stem cell niche, and show that it is altered in MMTV-c-myc and likely altered in MT TGFα transgenic epithelia.

Tissue & Cell, Jan 1, 2003

There is now strong evidence that the stem cells of many tissues reside in specialized structures... more There is now strong evidence that the stem cells of many tissues reside in specialized structures termed niches. The stem cell niche functions to house and regulate symmetric and asymmetric mitosis of stem cells in mammalian skin, mouse and human bone marrow, mouse brain, gut, and hair follicle, and Drosophila ovary and testis. This regulation is effected through the action of various signaling pathways such as Notch, Hedgehog, Wnt and others. The hormones of the estrous cycle, pregnancy and lactation that initiate growth in mouse mammary epithelium appear to act at a paracrine level to regulate mitosis through Notch receptors. Previous work has established that the putative stem cells of the mammary epithelium in several animal species reside near the basement membrane and never make contact with the ductal lumen. We show that these putative stem cells are found in anatomically specialized places created by the cytoplasmic extensions and modifications of neighboring differentiated cells. Such specializations may help to regulate stem cell activity by modulating molecular traffic to putative stem cells and contact with signaling molecules in the basement membrane. The histological characteristics of these putative niches vary as to the kinds of relationships the cells can have with the basement membrane and neighboring cells and as to how many stem or progenitor cells they may contain. This suggests a plasticity that may be relevant to the response of niches to tissue demands, such as wound healing, the periodic growth and regression of mammary epithelium, the process of mammary tumorigenesis therapeutic strategies for breast cancer.

Journal of Endocrinology, Jan 1, 2000

It has recently been shown that the progeny froma single cell may comprise the epithelial populat... more It has recently been shown that the progeny froma single cell may comprise the epithelial population ofa fully developed lactating mammary outgrowth in mice.Serial transplantation of epithelial fragments from this clonally derived gland demonstratesthat the subsequently generated outgrowths are alsocomprised of progeny from the original antecedent.Similarly, genetic analysis of contiguous portions of individual human mammary ducts within the samebreast indicates their clonal derivation. Theseobservations support the concept that multipotenttissue-specific epithelial stem cells are present amongthe parenchymal cells of the mammary gland. Here,we present the developing evidence for the presence ofstem cells in virtually every renewing mammalian tissueas well as some classically considered to consist only of differentiated cells. Further, wereview the present morphologic and biologic evidence forstem cells and lineage-limited progenitor cells in humanand rodent mammary epithelium. Although a number of selective markers are known for variouslineage-limited hematopoietic cells and their progeny,our understanding of the biology of the precursor cellsfor mammary epithelium is just beginning. Our purpose here is to develop further interest in theclarification of these issues in the biology of themammary gland.

Tissue & Cell, Jan 1, 1997

Markers for the division-competent cells in mammary gland epithelium are important to the underst... more Markers for the division-competent cells in mammary gland epithelium are important to the understanding of normal and neoplastic mammary epithelial growth and architectural maintainence, but have been difficult to reveal. Using the presence of condensed chromosomes as an indicator of division competence, we have described morphological markers in the nucleus and cytoplasm that reliably characterize two sets of structurally-distinct, division-competent cells in murine (i.e. mouse and rat) mammary epithelium. The markers, based, in part, on cell size, nuclear and cytoplasmic staining characteristics, and distinctive morphological features of the nucleus and cytoplasm allow classification of the division-competent cells into two categories: ‘large light cells’ and ‘small light cells’. Based on the degree of cytoplasmic organelle differentiation, the small light cells are the least differentiated cells in the epithelium, and the large light cells appear, structurally and functionally, to be in the early stages of secretory differentiation. We demonstrate, using statistical analysis of cell counts (per unit area of epithelium) from four stages of mammary epithelial growth, that there are, in fact, three division-competent cell populations in the rat mammary epithelium, and that the large light cell is a direct precursor to terminally differentiated cells, both secretory and myoepithelial. Using our results we synthesize a morphological model of cell mitosis and the progression of epithelial differentiation in murine mammary gland from a stem cell through two progenitors.

Microscopy Research and Technique, Jan 1, 2001

It has recently been shown that the progeny from a single cell may comprise the epithelial popula... more It has recently been shown that the progeny from a single cell may comprise the epithelial population of a fully developed lactating mammary outgrowth in mice. Serial transplantation of epithelial fragments from this clonally derived gland demonstrates that the subsequently generated outgrowths are also comprised of progeny from the original antecedent. All epithelial cell types were found to be present within these clonal normal populations including luminal, myoepithelial, ductal, and lobule-committed epithelial progenitors and fully competent mammary epithelial stem cells. These observations demonstrate the presence of multipotent tissue-specific epithelial stem cells among the parenchyma of the murine mammary gland. Similarly, genetic analysis of contiguous portions of individual human mammary ducts within the same breast indicates their clonal derivation. Here, we discuss the properties, location, division-potential, senescence, and plasticity associated with mammary epithelial stem cells and present the developing evidence for their presence in human breast and their important role in the risk for breast cancer development. Further, we review the present morphologic and genetic evidence for the characterization of specific stem cell markers and lineage-limited progenitor cells in human and rodent mammary epithelium.