Mouse Mammary Cancer Models - Mechanisms and Markers

Mouse Mammary Cancer Models - Mechanisms and Markers PDF Author:
Publisher:
ISBN:
Category :
Languages : en
Pages : 0

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Book Description
We have generated and characterized several mouse models to better understand the role of breast cancer associated genes in an e.

Mouse Mammary Cancer Models - Mechanisms and Markers

Mouse Mammary Cancer Models - Mechanisms and Markers PDF Author:
Publisher:
ISBN:
Category :
Languages : en
Pages : 0

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Book Description
We have generated and characterized several mouse models to better understand the role of breast cancer associated genes in an e.

Perspectives in Mammary Gland Development and Breast Cancer Research

Perspectives in Mammary Gland Development and Breast Cancer Research PDF Author: Zuzana Koledova
Publisher: Frontiers Media SA
ISBN: 288966094X
Category : Science
Languages : en
Pages : 158

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Book Description
This eBook is a collection of articles from a Frontiers Research Topic. Frontiers Research Topics are very popular trademarks of the Frontiers Journals Series: they are collections of at least ten articles, all centered on a particular subject. With their unique mix of varied contributions from Original Research to Review Articles, Frontiers Research Topics unify the most influential researchers, the latest key findings and historical advances in a hot research area! Find out more on how to host your own Frontiers Research Topic or contribute to one as an author by contacting the Frontiers Editorial Office: frontiersin.org/about/contact.

Mouse Models of Human Cancer

Mouse Models of Human Cancer PDF Author: Eric C. Holland
Publisher: John Wiley & Sons
ISBN: 047144460X
Category : Science
Languages : en
Pages : 504

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Book Description
Mice have become the species of choice for modeling the complex interactions between tumor cells and the host environment. Mouse genetics are easily manipulated, and a growing array of technology exists for this purpose. Mouse models allow investigators to better understand causal relationships between specific genetic alterations and tumors, utilize new imaging techniques, and test novel therapies. Recent developments along these lines show great promise for the development of new anti-cancer treatments. Mouse Models of Human Cancer provides researchers and students with a complete resource on the subject, systematically presenting the principles, methodologies, applications, and challenges associated with this exciting field. Offering a survey of the latest research and a description of future areas of interest, this text: Presents real experimental data Describes organ site-specific mouse models Clearly identifies suitable models for further drug testing Critically analyzes current methodologies and their limitations Features numerous recognizable expert contributors Lists key Web sites, reagents, and companies From mouse handling and genetic engineering to preclinical trials, Mouse Models of Human Cancer is a comprehensive guide to using these models and relating them to human disease. Its uniform presentation describes organ-specific models in clinical, imaging, and molecular terms, and lays out the relevant genetics, experimental approaches, histological comparisons with human disease, and conclusions. Combining stellar chapter authors, rich illustrations, and clear, up-to-date coverage, Mouse Models of Human Cancer is an invaluable resource for advanced students and cutting-edge researchers.

Heterogeneity in Mammary Cancer

Heterogeneity in Mammary Cancer PDF Author: Allison Cleary
Publisher:
ISBN:
Category :
Languages : en
Pages :

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Book Description
Breast cancer is a heterogeneous disease on two levels. First, breast cancers display inter-tumor heterogeneity evidenced by the diversity of clinically and molecularly defined tumor subtypes that differ with respect to disease progression and drug sensitivity. Second, individual breast cancers display remarkable intra-tumor heterogeneity evidenced by the diversity of component tumor cell subtypes co-residing within each cancer that differ with respect to cell morphology, proliferation rate, metastatic potential, drug sensitivity, and capacity for tumor reconstitution. The cellular mechanisms that generate and maintain breast cancer heterogeneity, both at the level of tumor subtype and tumor cell subtype, remain poorly understood. Using mouse models of human breast cancer, this dissertation examines whether and how breast cancer heterogeneity derives from the diverse and highly interactive cell subtypes that comprise the normal mammary gland, breast cancer's tissue-of-origin.In one set of experiments directed at uncovering the origin of tumor subtypes, we examined why transgenic mouse models of breast cancer nearly always yield a hormone receptor (HR)-negative mammary cancer subtype. In the mammary gland, mature ducts consist of basal and luminal mammary epithelial cell (MEC) subtypes. The luminal epithelial compartment can be further subdivided into hormone receptor (HR)-positive and HR-negative subsets. While human breast cancers frequently express HRs and depend on ovarian hormones for growth, transgenic mouse models of breast cancers show an unexplained bias toward HR-negative disease. Since the majority of mouse breast cancer models use the mouse mammary tumor virus long terminal repeat (MMTV-LTR) as a mammary-specific promoter element, we examined whether MMTV targets transgene expression to a specific MEC compartment. Using the MMTV-LTR to drive expression of a nuclear H2BGFP reporter transgene, we observed nuclear labeling restricted to HR-negative cells within the luminal compartment. Combining this labeling strategy with MMTV-directed expression of the Neu oncogene, we found Neu transgene expression was similarly enriched within HR-negative luminal MECs. Further, Neu-initiated neoplasias were comprised entirely of HR-negative cells from the carcinoma-in-situ stage onward. Thus, MMTV-driven Neu expression targets HR-negative luminal cells, culminating in HR-negative tumors. We propose that the HR-negative phenotype of many mouse breast cancer models can be explained by MMTV-driven transgene expression in HR-negative MECs. In another set of experiments, we sought to study interactions between tumor cell subtypes. To do this, we developed a novel experimental platform for culturing chimeric mammary organoids which permits analysis of both the cell-autonomous and non-autonomous effects of oncogene expression. By combining primary MECs from two different transgenic donors, chimeric mammary organoids were assembled consisting of intermingled populations of genetically distinct donor MECs that could each be tracked over time. We tested our system using transgenic mouse models engineered to inducibly express either an activated HRas allele or oncogenic Wnt1 in specific MECs. As expected, HRas-expressing cells expanded in number, which is consistent with a predominantly cell autonomous role for oncogenic HRas. By contrast, Wnt1-expressing cells did not expand in number. Instead, luminal expression of Wnt1 produced a dramatic and selective expansion of the basal epithelial cell compartment, as captured by live cell imaging. Thus, secreted Wnt1 primarily drove MEC overgrowth by acting in a paracrine rather than autocrine manner. Overall, chimeric organoid analysis can be used as a sensitive and effective tool for studying complex cell-cell interactions in the context of both normal and transformed mammary epithelium. In a final set of experiments directed at explaining how diverse tumor cell subtypes are maintained within mammary cancers, we examined the functional relationship between distinct tumor cell clones. Recent studies highlight the phenotypic and genetic diversity present locally within individual breast tumors, but whether this heterogeneity is a cause or a consequence of tumor progression remains unclear. Here, we used mouse models of breast cancer to demonstrate for the first time that interclonal cooperation can be essential for tumor maintenance. Aberrant expression of the secreted signaling molecule Wnt1 generates mixed-lineage mammary tumors composed of basal and luminal tumor cell subtypes, which purportedly derive from a bipotent malignant progenitor cell residing atop a tumor cell hierarchy. Using somatic HRas mutations as clonal markers, we showed that some Wnt tumors indeed conformed to a hierarchical configuration, but others unexpectedly harbored genetically distinct basal HRas mutant (HRasmut) and luminal HRas wild-type (HRaswt) subclones. Both subclones were required for efficient tumor propagation, which strictly depended on luminally-produced Wnt1. When biclonal tumors were challenged with Wnt withdrawal to simulate targeted therapy, analysis of tumor regression and relapse revealed that basal subclones recruited heterologous Wnt-producing cells to restore tumor growth. Alternatively, in the absence of a substitute Wnt source, the original subclones often evolved to rescue Wnt pathway activation and drive relapse, either by restoring cooperation or by switching to a defector strategy. Uncovering similar modes of interclonal cooperation in human cancers may inform efforts aimed at eradicating tumor cell communities.

Molecular Oncology of Breast Cancer

Molecular Oncology of Breast Cancer PDF Author: Jeffrey Stuart Ross
Publisher: Jones & Bartlett Learning
ISBN: 9780763748104
Category : Medical
Languages : en
Pages : 642

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Book Description
The first comprehensive reference to focus on the molecular development and treatment of the disease, Molecular Oncology of Breast Cancer provides authoritative information across the spectrum of modern breast cancer research and clinical care. Edited by two world-class experts in cancer pathology, drug development, and patient management, with contributions from over 50 experts, this ground-breaking text describes the genes, proteins, and biologic pathways that are being evaluated today and will be tested in the future to derive the molecular signature of each newly diagnosed breast cancer. For the first time, readers can now obtain, in a single volume, up-to-date information on how molecular-based tests are being used to identify predisposition, provide earliest detection, decide classification based on genetic fingerprint and predict therapy-specific outcomes. MOBC includes unique chapters on functional imaging and the impact of targeted therapies on the FDA approval process. This book gives readers vital, up-to-date information on important molecular discoveries that affect the everyday management of the breast cancer patient.

The Heterogeneity of Cancer Metabolism

The Heterogeneity of Cancer Metabolism PDF Author: Anne Le
Publisher: Springer
ISBN: 331977736X
Category : Medical
Languages : en
Pages : 186

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Book Description
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.

Viral Gastroenteritis

Viral Gastroenteritis PDF Author: Shunzo Chiba
Publisher: Springer Science & Business Media
ISBN: 3709165539
Category : Medical
Languages : en
Pages : 301

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Book Description
Recently, rapid developments have occurred in the field of viral gastroenteritis. This book is an update of fundamental and practical aspects of viral gastroenteritis. Among the various agents that cause viral gastroenteritis, group A rotaviruses and caliciviruses are the focus of this volume because of their clinical impact and the significance of new findings about them.

Mouse Models of Cancer

Mouse Models of Cancer PDF Author: Cory Abate-Shen
Publisher:
ISBN: 9781621820031
Category : Medical
Languages : en
Pages : 0

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Book Description
The laboratory mouse is an important model for addressing questions in cancer biology. In recent years, the questions have become more refined, and mouse models are increasingly being used to develop and test cancer therapeutics. Thus, the need for more sophisticated and clinically relevant mouse models has grown, as has the need for innovative tools to analyze and validate them. This laboratory manual provides cutting-edge methods for generating and characterizing mouse models that accurately recapitulate many features of human cancer. The contributors describe strategies for producing genetic models, including transgenic germline models, gene knockouts and knockins, and conditional and inducible systems, as well as models derived using transposon-based insertional mutagenesis, RNA interference, viral-mediated gene delivery, and chemical carcinogens. Tissue recombination, organ reconstitution, and transplantation methods to develop chimeric, allograft, and xenograft models are covered. Approaches to characterize tumor development, progression, and metastasis in these models using state-of-the-art imaging, histopathological, surgical, and other techniques are also included. Other chapters cover the use of mouse models to test and optimize drugs in pre-, co-, and post-clinical trials. An appendix specifically addresses the use of mouse cancer models in translational studies and the integration of mouse and human clinical investigations. This manual is therefore an indispensable laboratory resource for all researchers, from the graduate level upwards, who study cancer and its treatment.

MicroRNAs in Cancer

MicroRNAs in Cancer PDF Author: Cesar Lopez-Camarillo
Publisher: CRC Press
ISBN: 1466576774
Category : Medical
Languages : en
Pages : 426

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Book Description
MicroRNA (miRNA) biology is a cutting-edge topic in basic as well as biomedical research. This is a specialized book focusing on the current understanding of the role of miRNAs in the development, progression, invasion, and metastasis of diverse types of cancer. It also reviews their potential for applications in cancer diagnosis, prognosis, and th

Scientific Reports on the Investigations of the Cancer Research Fund

Scientific Reports on the Investigations of the Cancer Research Fund PDF Author: Cancer Research Fund (Great Britain)
Publisher:
ISBN:
Category : Cancer
Languages : en
Pages : 288

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Book Description