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Category :
Languages : en
Pages : 23
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To understand the multi-step process of mammary tumorigenesis, we have compared gene expression profiles in different stages of mammary oncogenesis in MMTV-Wnt- 1 transgenic mice. Specifically, we have collected tissue samples from virgin mammary glands, hyperplastic mammary glands, Wnt- 1 mammary tumors, and tumors metastasized to the lung, and compared their gene expression patterns. Hierarchical clustering analysis and multidimensional scaling analysis showed that gene expression profiles are associated with tumor progression. Each sample group from the same stage cluster separately from samples at other stages. Using the statistical analysis permutation t-test, I identified groups of genes differentially expressed in each of the stages. I also identified a group of genes as potential direct or indirect target genes of Wnt signaling since they are only regulated in mammary tumors induced by the MMTV-Wnt-1 transgene in comparison with tumors induced by other transgenes such as (MMTV)-c-myc, MMTV-Ha-ras, MMTV-neu, MMTV-polyoma middle T antigen, C3(l)/simian virus 40 T/t antigen, and WAP-SV4O T/t antigen (Desai et al., 2002). In addition, I established gene expression profiles for mammary tumors induced by Wntl, and by Wnt1 in cooperation with loss of tumor suppressor genes such as Pten or P53.
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Languages : en
Pages : 0
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The purpose of the proposed research is to establish the cDNA microarray technology in the study of mouse mammary tumor development induced by Wnt1 proto-oncogene. We also propose to identify downstream target genes of the Wnt- 1 signaling pathway in mouse mammary epithelial C57MG cells as well as in the human kidney epithelial 293 cells. We have printed the first prints of mouse unigene cDNA microarray chips which contain about 5,000 cDNA clones. The second prints will include about 10,000 cDNA clones and is currently in preparation stage. These prints will be used to identify gene expression patterns of the normal mouse mammary gland tissue samples and mouse mammary tumor samples from the MMTV-Wnt-1 transgenic mice. Such parallel analysis of gene expression profiles may provide insights into the mechanisms underlying mouse mammary tumorigenesis and provide molecular markers for diagnosis and prognosis of mammary tumors. We are also establishing cell culture systems to acutely initiate Wnt- 1 signaling suitable for the identification of downstream target genes in the mouse mammary cells as well as in human cells. Currently, we have developed mouse mammary cell line that can be readily infected by avian leukosis virus that carry specific genes of interest (such as Wnt-I). Inducible cell lines that express Wnt-1, beta-catenin, or Lef-1 proteins has also been established in the human 293 cells. These cell culture system will provide useful tools to identify downstream responsive genes of the Wnt-1 signaling pathway. These research may also provide new targets for intervention and novel strategies for treatment of mammary tumors.
Author: Shaoguang Li
Publisher: World Scientific
ISBN: 9812790462
Category : Science
Languages : en
Pages : 131
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Book Description
DNA microarray technology has become a useful technique in gene expression analysis for the development of new diagnostic tools and for the identification of disease genes and therapeutic targets for human cancers. Appropriate control for DNA microarray experiment and reliable analysis of the array data are key to performing the assay and utilizing the data correctly. The most difficult challenge has been the lack of a powerful method to analyze the data for all genes (more than 30,000 genes) simultaneously and to use the microarray data in a decision-making process. In this book, the authors describe DNA microarray technology and data analysis by pointing out current advantages and disadvantages of the technique and available analytical methods. Crucially, new ideas and analytical methods based on the authors'' own experience in DNA microarray study and analysis are introduced. It is believed that this new way of interpreting and analyzing microarray data will bring us closer to success in decision-making using the information obtained through the DNA microarray technology.
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Category :
Languages : en
Pages : 10
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DNA microarray technology has revolutionized the way we study gene expression in different biological systems. With this technique, gene expression profiles from two or more samples can be conveniently analyzed using isolated steady state RNA. While this approach works well when comparing the steady-state levels of gene expression of different samples, measurements of inducible gene expression responses may be compromised by the inclusion of pre-existing steady state RNA in the analysis. In response to DNA-damaging agents, cells induce signal transduction pathways that ultimately lead to the reprogramming of the expression of certain genes. Previous studies of inducible gene expression profiles have used steady- state levels of RNA as starting material for DNA microarray experiments.
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Category :
Languages : en
Pages : 0
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We have transfected the 184B5 immortalized, non-transformed human mammary epithelial cell line with the oncogenic mutant ras gene and with empty vector. We have isolated the following stable transfecants: (1) cells overexpressing the mutant ras oncogene (2) cells overexpressing the normal, non-mutant form of ras (3) cells transfected with the empty vector. The first group of clones is being sorted by their ability to form tumors. We are currently performing cDNA microarray analysis quantifying the expression level of about 15,000 genes in these cell lines. We have also performed cDNA micorarray analysis on several established breast cancer derived cell lines. The comparative analysis will reveal the gene expression similarity between the cell lines that were transformed by the ras oncogene. This will determine whether gene expression patterns could be used to infer that certain breast tumor samples were originated, at least partially, by the ras oncogene. We are also comparing the gene expression patterns derived from in vitro transformed cells to the gene expression profile of primary breast tumors and established breast cancer cell lines. This will help to assess the ratio of gene expression changes in primary breast tumors that could be attributed to the presence of the above listed oncogenic changes. If this ratio is low, then the potential role of other oncogenic factors in the development of breast cancer will be substantiated. The opposite result will support the definitive role of these already known oncogenes in sporadic breast cancer. We will also compare the tumor forming and the non-malignant clones that both overexpress the ras oncogenes and determine which ras inducible genes are relevant for tumor formation.
Author: Bert W. O'Malley
Publisher:
ISBN:
Category : Cyclic nucleotides
Languages : en
Pages : 488
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Book Description
Hormone assays; Hormone receptors; Evaluation of biological effects of hormones; Purification and synthesis of hormones.
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ISBN: 9780815332183
Category : Cells
Languages : en
Pages : 0
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Author: Guillermina Lozano
Publisher:
ISBN: 9781621821335
Category : Medical
Languages : en
Pages : 0
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Book Description
Decades of research on the tumor suppressor p53 have revealed that it plays a significant role as a "guardian of the genome," protecting cells against genotoxic stress. In recent years, p53 research has begun to move into the clinic in attempts to understand how p53 is frequently inactivated in-and sometimes even promotes-human cancer. Written and edited by experts in the field, this collection from Cold Spring Harbor Perspectives in Medicine covers the rapid progress that has recently been made in basic and clinical research on p53. The contributors review new observations about its basic biology, providing updates on the functions of its isoforms and domains, the myriad stresses and signals that trigger its activation or repression, and its downstream effects on genome stability and the cell cycle that enforce tumor suppression in different cell and tissue types. They also discuss how p53 dysfunction contributes to cancer, exploring the various inherited and somatic mutations in the human TP53 gene, the impact of mutant p53 proteins on tumorigenesis, and the prognostic value and clinical outcomes of these mutations. Drugs that are being developed to respond to tumors harboring aberrant p53 are also described. This book is therefore essential reading for all cancer biologists, cell and molecular biologists, and pharmacologists concerned with the treatment of this disease.
Author: Guido Bocci
Publisher: Springer
ISBN: 3662436043
Category : Medical
Languages : en
Pages : 302
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Book Description
This book analyzes all aspects of metronomic chemotherapy, a new approach involving low-dose, long-term, and frequently administered therapy that has preclinical and clinical activity in various tumors. After an opening section on the pharmacological bases of metronomic chemotherapy, including its antiangiogenic effects and impact on immunity, preclinical studies on various classes of drug are discussed. Clinical applications of metronomic chemotherapy in a wide variety of tumors are then addressed in detail, with description of the results of all published studies. The clinical pharmacology of metronomic chemotherapy is also considered in depth, encompassing pharmacokinetics, pharmacogenetics, pharmacoeconomics, and adverse drug reactions. The book closes by describing the role of this therapy in the veterinarian clinic.
Author: Phuc Van Pham
Publisher: BoD – Books on Demand
ISBN: 9535129996
Category : Medical
Languages : en
Pages : 570
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Book Description
Breast Cancer - From Biology to Medicine thoroughly examines breast cancer from basic definitions, to cellular and molecular biology, to diagnosis and treatment. This book also has some additional focus on preclinical and clinical results in diagnosis and treatment of breast cancer. The book begins with introduction on epidemiology and pathophysiology of breast cancer in Section 1. In Section 2, the subsequent chapters introduce molecular and cellular biology of breast cancer with some particular signaling pathways, the gene expression, as well as the gene methylation and genomic imprinting, especially the existence of breast cancer stem cells. In Section 3, some new diagnostic methods and updated therapies from surgery, chemotherapy, hormone therapy, immunotherapy, radiotherapy, and some complementary therapies are discussed. This book provides a succinct yet comprehensive overview of breast cancer for advanced students, graduate students, and researchers as well as those working with breast cancer in a clinical setting.
