Download or read book Gene Expression Profiling of the Breast Tumour Microenvironment written by Grzegorz Finak and published by . This book was released on 2008 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: "Breast cancer is a very heterogeneous disease. This heterogeneity can be observed at many levels, including gene expression, chromosomal aberrations, and disease pathology. A clear understanding of these differences is important since they impact upon treatment efficacy and clinical outcome. Recent studies have demonstrated that the tumour microenvironment also plays a critical role in cancer initiation and progression. Genomic technologies have been used to gain a better understanding of the impact of gene expression heterogeneity on breast cancer, and have identified gene expression signatures associated with clinical outcome, histopathological breast cancer subtypes, and a variety of cancer-related pathways and processes. However, little work has been done in this context to examine the role of the tumour microenvironment in determining breast cancer outcome, or in defining breast cancer heterogeneity. Additionally, little is known about gene expression in histologically normal tissue adjacent to breast tumour, if this is influenced by the tumour, and how this compares with non-tumour-bearing breast tissue. By applying laser--capture microdissection and gene expression profiling to clinical breast cancer specimens the research presented in this thesis addresses these questions. We have generated gene expression profiles of morphologically normal epithelial and stromal tissue, isolated using laser capture microdissection, from patients with breast cancer or undergoing breast reduction mammoplasty. We determined that morphologically normal epithelium and stroma exhibited distinct expression profiles, but molecular signatures that distinguished breast reduction tissue from tumour-adjacent normal tissue were absent. Stroma isolated from morphologically normal ducts adjacent to tumour tissue contained two distinct expression profiles that correlated with stromal cellularity, and shared similarities with soft tissue tumors with favourable outcome. Adjacent normal epithelium and stroma from breast cancer patients showed no significant association between expression profiles and standard clinical characteristics, but did cluster ER/PR/HER2-negative breast cancers with basal-like subtype expression profiles with poor prognosis. Our data reveal that morphologically normal tissue adjacent to breast carcinomas has not undergone significant gene expression changes when compared to breast reduction tissue, and provide an important gene expression data set for comparative studies of tumour expression profiles. We compared gene expression profiles of tumour stroma from primary breast tumors and derived signatures strongly associated with clinical outcome. We present a new stroma-derived prognostic predictor (SDPP) that stratifies disease outcome independently of standard clinical prognostic factors and published expression-based predictors. The SDPP predicts outcome in several published whole tumour--derived expression data sets, identifies poor-outcome individuals from multiple clinical subtypes, including lymph node--negative tumors, and shows increased accuracy with respect to previously published predictors, especially for HER2-positive tumors. Prognostic power increases substantially when the predictor is combined with existing outcome predictors. Genes represented in the SDPP reveal the strong prognostic capacity of differential immune responses as well as angiogenic and hypoxic responses, highlighting the importance of stromal biology in tumour progression. We show that gene expression in the breast tumour microenvironment is highly heterogeneous, identifying at least six different classes of tumour stroma with distinct expression patterns and distinct biological processes. Two of these classes recapitulate the processes identified in the stroma-derived prognostic predictor, while the others are new classes of stroma associated with distinct clinical outcomes. One of these is associated with matrix remodelling and is strongly associated with the basal molecular subtype of breast cancer. The remainder are independent of the previously published molecular subtypes of breast cancer. Additionally, based on independent data from over 800 tumors, the combinations of stroma classes and breast cancer subtypes identify new subgroups of breast tumors that show better discrimination between good and poor outcome individuals than the molecular breast cancer subtypes or the stroma classes alone, suggesting a novel classification scheme for breast cancer. This research demonstrates an important role for the tumour microenvironment in defining breast cancer heterogeneity, with a consequent impact upon clinical outcome. Novel therapies could be targeted at the processes that define the stroma classes suggesting new avenues for individualized treatment."--

Download or read book Gene Expression Profiling of the Breast Tumour Microenvironment and Its Influence on Clinical Outcome written by Grzegorz Finak and published by . This book was released on 2008 with total page 554 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book Impact of Gene Expression Profiling Tests on Breast Cancer Outcomes written by Luigi Marchionni and published by DIANE Publishing. This book was released on 2009-05 with total page 230 pages. Available in PDF, EPUB and Kindle. Book excerpt: Assesses the evidence that three marketed gene expression-based assays improve prognostic accuracy, treatment choice, and health outcomes in women diagnosed with early stage breast cancer. Three gene expression assays were evaluated; Oncotype DX¿, MammaPrint® and the Breast Cancer Profiling (BCP or H/I ratio) test, and for gene expression signatures underlying the assays. They sought evidence on: analytic performance of tests; clinical validity; clinical utility; harms; and impact on clinical decision making and health care costs. Conclusions: Oncotype DX is furthest along the validation pathway, with retrospective evidence that it predicts distant spread and chemotherapy benefit to a clinically relevant extent over standard predictors. Illus.

Download or read book Bioinformatics Approaches to Understanding the Breast Cancer Microenvironment written by François Pepin and published by . This book was released on 2010 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book A Comparison of Gene Expression Profiling Tests for Breast Cancer written by Pam Smartt and published by . This book was released on 2010 with total page 102 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book Impact of Gene Expression Profiling Tests on Breast Cancer Outcomes written by Luigi Marchionni (M.D.) and published by . This book was released on 2008-01-01 with total page 105 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book Defining Microenvironment induced Transcription Profiles in Breast Cancer Liver Metastases written by Christine Tam and published by . This book was released on 2014 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: "Breast cancer is the most common type of cancer diagnosed in Canadian women, with metastatic spread contributing to the majority of cancer-related deaths. The liver is the third most frequent site of breast cancer metastasis, but not much is known about the hepatic microenvironment's role in regulating the growth and survival of metastatic cells in the liver. In order to elucidate these interactions, we used laser capture microdissection and microarray analysis to compare gene expression patterns of liver metastases and primary tumors. We employed liver-aggressive 4T1 breast cancer cells derived from an in vivo selection process to generate mammary tumors and liver metastases in female Balb/c mice. Mice with liver metastases were kept for three different time periods post-injection to assess the changes in gene expression during metastatic development. Laser capture microdissection was used to isolate cores and margins of tumors and liver metastases, as well as tumor-adjacent and -distal normal liver. Transcription profiling revealed significant gene expression changes within breast cancer cells growing in the fat pad and the liver microenvironments. We identified a set of immune-related genes overexpressed in the liver metastases that may represent putative myeloid/granulocytic cell markers. Lcn2 and S100a8/S100a9 were found to be exclusively expressed in the immune compartment of liver metastases, particularly within smaller lesions. Since concurrent studies in our laboratory have revealed a similar recruitment of Gr1+/NE+ cells around breast cancer liver metastases, Lcn2 and S100a8/a9 represent interesting avenues with which to investigate the role that these infiltrating cell types play in supporting breast cancer liver metastasis." --

Download or read book Advancing the Science of Cancer in Latinos written by Amelie G. Ramirez and published by Springer Nature. This book was released on 2019-11-21 with total page 320 pages. Available in PDF, EPUB and Kindle. Book excerpt: This open access book gives an overview of the sessions, panel discussions, and outcomes of the Advancing the Science of Cancer in Latinos conference, held in February 2018 in San Antonio, Texas, USA, and hosted by the Mays Cancer Center and the Institute for Health Promotion Research at UT Health San Antonio. Latinos – the largest, youngest, and fastest-growing minority group in the United States – are expected to face a 142% rise in cancer cases in coming years. Although there has been substantial advancement in cancer prevention, screening, diagnosis, and treatment over the past few decades, addressing Latino cancer health disparities has not nearly kept pace with progress. The diverse and dynamic group of speakers and panelists brought together at the Advancing the Science of Cancer in Latinos conference provided in-depth insights as well as progress and actionable goals for Latino-focused basic science research, clinical best practices, community interventions, and what can be done by way of prevention, screening, diagnosis, and treatment of cancer in Latinos. These insights have been translated into the chapters included in this compendium; the chapters summarize the presentations and include current knowledge in the specific topic areas, identified gaps, and top priority areas for future cancer research in Latinos. Topics included among the chapters: Colorectal cancer disparities in Latinos: Genes vs. Environment Breast cancer risk and mortality in women of Latin American origin Differential cancer risk in Latinos: The role of diet Overcoming barriers for Latinos on cancer clinical trials Es tiempo: Engaging Latinas in cervical cancer research Emerging policies in U.S. health care Advancing the Science of Cancer in Latinos proves to be an indispensable resource offering key insights into actionable targets for basic science research, suggestions for clinical best practices and community interventions, and novel strategies and advocacy opportunities to reduce health disparities in Latino communities. It will find an engaged audience among researchers, academics, physicians and other healthcare professionals, patient advocates, students, and others with an interest in the broad field of Latino cancer.

Download or read book Ex Vivo Engineering of the Tumor Microenvironment written by Amir R. Aref and published by Springer. This book was released on 2016-12-09 with total page 142 pages. Available in PDF, EPUB and Kindle. Book excerpt: This volume will outline how to recreate the tumor microenvironment, to culture primary tumors without the need for developmental priming factors, and to deliver targeted therapeutics in a manner that recapitulates pharmacokinetics in vivo. Much of what may be learned from this volume will aid in understanding many aspects of the enhanced study of tumor cell biology in a physiologic context, open new avenues for drug screening and biomarker development, and accelerate the preclinical evaluation of novel personalized medicine strategies for patients in real time.

Download or read book Tumor Microenvironment written by Peter P. Lee and published by Springer Nature. This book was released on 2020-03-25 with total page 326 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book addresses the biological processes relevant to the immune phenotypes of cancer and their significance for immune responsiveness, based on the premise that malignant cells manipulate their surroundings through an evolutionary process that is controlled by interactions with innate immune sensors as well as the adaptive recognition of self/non-self. Checkpoint inhibitor therapy is now an accepted new form of cancer treatment. Other immuno-oncology approaches, such as adoptive cell therapy and metabolic inhibitors, have also shown promising results for specific indications. Immune resistance is common, however, limiting the efficacy of immunotherapy in many common cancer types. The reasons for such resistance are diverse and peculiar to the immune landscapes of individual cancers, and to the treatment modality used. Accordingly, approaches to circumvent resistance need to take into account context-specific genetic, biological and environmental factors that may affect the cancer immune cycle, and which can best be understood by studying the target tissue and correlated systemic immune markers. Understanding the major requirements for the evolutionary process governing human cancer growth in the immune-competent host will guide effective therapeutic choices that are tailored to the biology of individual cancers.

Download or read book The Application of Gene Expression Profiling to Clinical Breast Cancer Research written by Sherene Loi and published by LAP Lambert Academic Publishing. This book was released on 2009 with total page 280 pages. Available in PDF, EPUB and Kindle. Book excerpt: The book has three main results parts. Chapter 3 illustrates the first independent validation study of a 70-gene signature developed from gene expression profiling for use in breast cancer prognosis and demonstration of its ability to add independent prognostic information to the clinical prognostic factors currently used. The successful validation of this study preceded the design and implementation of a world-wide randomized clinical trial evaluating the gene signature's clinical utility. This trial has commenced and is currently recruiting in Europe. Chapter 4 describes the finding that proliferation-related genes can predict clinical outcome consistently in breast cancer and many gene signatures developed for predicting breast cancer prognosis derive a significant proportion of their prognostic power from these genes. Finally, chapter 5 describes the use of proliferation-related genes to define two distinct prognostic molecular subgroups within estrogen receptor positive breast cancers.

Download or read book Targeted Therapies for Lung Cancer written by Ravi Salgia and published by Springer. This book was released on 2019-06-26 with total page 238 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book contextualizes translational research and provides an up to date progress report on therapies that are currently being targeted in lung cancer. It is now well established that there is tremendous heterogeneity among cancer cells both at the inter- and intra-tumoral level. Further, a growing body of work highlights the importance of targeted therapies and personalized medicine in treating cancer patients. In contrast to conventional therapies that are typically administered to the average patient regardless of the patient’s genotype, targeted therapies are tailored to patients with specific traits. Nonetheless, such genetic changes can be disease-specific and/or target specific; thus, the book addresses these issues manifested in the somatically acquired genetic changes of the targeted gene. Each chapter is written by a leading medical oncologist who specializes in thoracic oncology and is devoted to a particular target in a specific indication. Contributors provide an in-depth review of the literature covering the mechanisms underlying signaling, potential cross talk between the target and downstream signaling, and potential emergence of drug resistance.

Download or read book The Heterogeneity of Cancer Metabolism written by Anne Le and published by Springer. This book was released on 2018-06-26 with total page 186 pages. Available in PDF, EPUB and Kindle. Book excerpt: Genetic alterations in cancer, in addition to being the fundamental drivers of tumorigenesis, can give rise to a variety of metabolic adaptations that allow cancer cells to survive and proliferate in diverse tumor microenvironments. This metabolic flexibility is different from normal cellular metabolic processes and leads to heterogeneity in cancer metabolism within the same cancer type or even within the same tumor. In this book, we delve into the complexity and diversity of cancer metabolism, and highlight how understanding the heterogeneity of cancer metabolism is fundamental to the development of effective metabolism-based therapeutic strategies. Deciphering how cancer cells utilize various nutrient resources will enable clinicians and researchers to pair specific chemotherapeutic agents with patients who are most likely to respond with positive outcomes, allowing for more cost-effective and personalized cancer therapeutic strategies.

Download or read book Gene Expression Profiling of Hereditary Breast Cancer written by and published by . This book was released on 2002 with total page 95 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book Minimal Residual Disease and Circulating Tumor Cells in Breast Cancer written by Michail Ignatiadis and published by Springer Science & Business Media. This book was released on 2012-04-23 with total page 245 pages. Available in PDF, EPUB and Kindle. Book excerpt: This important book provides up-to-date information on a series of topical issues relating to the approach to minimal residual disease in breast cancer patients. It first explains how the study of minimal residual disease and circulating and disseminated tumor cells (CTCs/DTCs) can assist in the understanding of breast cancer metastasis. A series of chapters then discuss the various technologies available for the detection and characterization of CTCs and DTCs, pinpointing their merits and limitations. Detailed consideration is given to the relevance of CTCs and DTCs, and their detection, to clinical research and practice. The role of other blood-based biomarkers is also addressed, and the closing chapters debate the challenges facing drug and biomarker co-development and the use of CTCs for companion diagnostic development. This book will be of interest and assistance to all who are engaged in the modern management of breast cancer.

Download or read book Breast Cancer Lymphatic Dissemination Influence of Estrogen and Progesterone written by and published by . This book was released on 2008 with total page 30 pages. Available in PDF, EPUB and Kindle. Book excerpt: Breast cancers commonly spread to lymph nodes (LNs). If the primary tumors are estrogen receptor (ER) and/or progesterone receptor (PR) positive, then the likelihood that LN metastases express receptors exceeds 80%. We developed metastasis models using ZsGreen labeled MCF-7 and T47D human breast cancer cells. Tumors were tracked in living mice by whole-body imaging, and macrometastases or micrometastases were detected by intravital imaging or fluorescence microscopy. Tumor growth was estrogen dependent. To determine if the LN microenvironment alters estrogen-dependent gene expression, we developed a unique model to identify estradiol regulated genes in ER+ breast tumors and LN metastases. Fluorescent ER+ MCF-7 tumors were grown in ovariectomized nude mice supplemented with estradiol. Once axillary LN metastasis arose, estradiol was withdrawn (EWD), for 1 or 4 weeks, or continued, to assess estradiol responsiveness. On EWD, proliferation rates fell similarly in tumors and LN metastases. However, estradiol-dependent ER down-regulation and PR induction were deficient in LN metastases, indicating that ER transcriptional activity was altered in the LN. Cancer cells from estradiol treated and EWD primary tumors and matched LN metastases were isolated by laser capture microdissection. Global gene expression profiling identified transcripts that were regulated by the tissue microenvironment, by hormones, or by both. Interestingly, numerous genes that were estradiol regulated in tumors lost estradiol sensitivity or were regulated in the opposite direction by estradiol in LN metastases. We propose that the LN microenvironment alters estradiol signaling and contributes to antiestrogen resistance.

Download or read book Cell Type Specific MRNA Amplification and Expression Profiling from Breast Tumor Sections written by and published by . This book was released on 2000 with total page 13 pages. Available in PDF, EPUB and Kindle. Book excerpt: The evolution of solid tumors involves acquisition of genetic abnormalities, which result in changes in both the set of genes expressed and the relative levels of gene expression. However, the increasing number of candidate genes whose expression needs to be evaluated for prognostic, diagnostic, therapeutic, or research purposes will require obtaining material from numerous tissue sections. Therefore this proposal is motivated by the need for more effective use of clinical specimens, and will address the problem of obtaining sufficient and cell type specific mRNA from clinical breast tumor specimens. This will entail adapting/developing procedures to amplify with fidelity the mRNA repertoire expressed in small numbers of normal, pre-cancerous and malignant breast epithelia. To this end, in this project period, we have concentrated effort on establishing and validating microarray-based assays for measuring gene expression levels and have demonstrated the capability to isolate and amplify mRNA from cultured cells. Realization of these objectives will allow, in the future, development of a resource, consisting of amplified mRNA populations from individual cells from normal and tumor material, that can be used for evaluation of the prognostic, diagnostic and/or therapeutic importance of genes expressed in breast cancer.