Apc

APC has been identified as a tumor suppressor gene and is mutated in both sporadic and hereditary colorectal tumorigenesis. The allelic loss of the APC gene on chromosome 5q21 is a frequent genetic alteration occurring in 40 of NSCLC (Cooper et al. 1996). Nevertheless, no mutation was found in the APC gene, by single-strand conforma-tional polymorphism analysis, in the 32 tumors described in the study above (Cooper et al. 1996). Other experiments similarly failed to find APC mutations in 55...

The PTCH Receptors

As shown by in situ hybridization, Ptchl is expressed in both ectoder-mally derived epithelium and mesodermally derived mesenchyme after mammary placode formation (as early as day 12.5) (Michno et al. 2003) and shows slightly reduced levels in the epithelial bulb relative to the overlying ectoderm at E14 (Boras-Granic et al. 2006 Lewis et al. 1999). Similarly, during ductal development, Ptchl mRNA is expressed in the body cells of the TEB, in differentiated ducts, and in the periductal stroma,...

The Paradox of Response and Survival

A cardinal principle of cancer therapeutics has been that evidence of a clinical response will translate into improved survival. The major advantage of using clinical response as the primary end point of thera peutic trials is that it is measurable over weeks to months, allowing the stepwise process of drug development to occur more rapidly and efficiently. In contrast, demonstrating a survival benefit adds significant complexity to clinical trial design, usually requiring the accrual of large...

CMyc and Activated Ras During Skin Tumorigenesis Cooperation at the Cancer Stem Cell Level

Swiss Institute for Experimental Cancer Research (ISREC), Ch. des Boveresses 155, CH-1066 Epalinges, Switzerland email Andreas.Trumpp isrec.ch 1 The Myc 2 Distinct Consequences of c-Myc Overexpression in Epidermal Cell 3 The Role of Endogenous c-Myc in the Epidermis 17 in Ras-Mediated Skin in Epidermal Cancer Initiating Cells 19 Abstract. Mutations leading to overexpression and activation of the oncogenes Myc and Ras are among the most frequent lesions known to occur in human and murine...

The Dandelion Phenomenon

Emerging data from some of the most successful new anticancer agents have helped shed light on this paradox that response and survival are not always linked. Imatinib has replaced interferon-a as the standard of care for newly diagnosed CML patients, based on an interim analysis of a multicenter, randomized trial showing higher response rates for imatinib (O'Brien et al. 2003). With up to 5 years of follow-up, most of the complete cytogenetic remissions to imatinib remain durable (Roy et al....

Eliminating Cancer Stem Cells

Currently, the search for novel anticancer therapies is primarily focused on oncogenes that are specific for (e.g., BCR-ABL in CML), or overex-pressed in (e.g., c-myc or bcl-2), selected cancers. However, attacking cancer-specific targets has met with variable success, and many of the most effective anticancer therapies, such as rituximab in lymphomas, high-dose cytotoxic therapy, or the allogeneic graft-versus-tumor effect, show limited or even no tumor selectivity. Targeting a cancer-specific...

Human Diseases Linked to Inherited Defects in DNA Repair Genes

Numerous human diseases are associated with defects of DNA repair. Many of these are associated with stem cell failure syndromes, malignant transformation, and or premature aging Table 1 . For instance, the Fanconi anemias complementation groups, FANC A, FANC C, FANC G, FANC D1, FANC D2, and FANC F, all have abnormalities in DNA double-strand break pair processing Yamashita and Nakahata 2001 . Mutations in these genes are associated with multiple physical abnormalities, mental retardation,...

Could Activated Hedgehog Signaling Regulate Breast Cancer Stem Cells

If, in fact, activated hedgehog signaling regulates behavior of normal mammary epithelial stem cells, it is entirely possible that it might also influence the behavior of breast cancer-initiating cells or breast cancer stem cells. In their study of hedgehog regulation of normal mammary epithelial stem progenitor cell self-renewal, Liu and colleagues explored this possibility Liu et al. 2006 . With CD44 CD24- low Lin cells isolated from a xenograft of a metastatic human breast cancer, the...

Wnt Signaling in Stem Cells and Lung Cancer

Wnt Lung Cancer

Department of Surgery, University of California San Francisco Cancer Center, 1600 Divisadero Street, Box 1724, 94143-1724 San Francisco, USA email jablonsd surgery.ucsf.edu 1 Overview of Wnt Signaling 28 1.1 Wnt 1.2 Wnt Receptors and Antagonists 29 1.3 Canonical Wnt Signaling Cytosolic and Nuclear Components 30 2 Stem Cells, Cancer Stem Cells, and Lung Cancer 31 3 Wnt Signaling in Stem Cell Maintenance and Regeneration 35 4 Wnt Signaling in Lung Cancer 37 4.1 Wnt 4.2 Wnt 4.3 Dishevelled Dvl 40...

List of Editors and Contributors

German Cancer Research Centre DKFZ , Im Neuenheimer Feld 280, 69120 Heidelberg, Germany e-mail o.wiestler dkfz.de Therapeutic Research Group Oncology, Bayer Schering Pharma AG, M llerstr. 178, 13342 Berlin, Germany e-mail Therapeutic Research Group Oncology, Bayer Schering Pharma AG, M llerstr. 178, 13342 Berlin, Germany e-mail 5117 Centre Avenue, Suite 2.42, Pittsburgh, PA 15213, USA Pathological Anatonomical Institute, Friedrich-Alexander-University N rnberg, 90154 Erlangen, Germany...

Can Hedgehog Signaling Antagonists Be Used for the Treatment of Breast Cancer

Hedgehog signaling inhibitors have been used successfully in vitro to inhibit growth of a variety of cancer cell lines and in vivo for the treatment of medulloblastoma Berman et al. 2002 Romer et al. 2004 . Amazingly, mice treated with these agents show little evidence of adverse side effects. If, indeed, activated hedgehog signaling plays a role in breast cancer development or progression, perhaps directly within the stem cells themselves or indirectly via a paracrine mechanism, small-molecule...

Bone Morphogenetic Proteins Regulate Tumorigenicity in Human Glioblastoma Stem Cells

Vescovi lt gt Stemgen s.p.a, Department of Biotechnology and Biosciences, University of Milan-Bicocca, Piazza della Scienca 2, 20126 Milan, Italy email vescovi.angelo hsr.it 1 Materials and Methods 75 1.2 Primary Culture, Culture Propagation, Cloning and Cell Line 1.4 Conventional and Real-Time PCR 77 1.5 Flow Cytometry Analysis 77 1.6 Evaluation of Tumorigenicity by Orthotopic Injection and Abstract. Human glioblastomas appear to be established and expanded by cancer...

Niche for Normal and Cancer Stem Cells

Center for Developmental Biology, Chuoku Minatojimaminamimachi 2-3-3, 2 The Melanocyte Stem Cell Serves as an Ideal Model to Understand Quiescence of Stem Cells 3 3 Definition of 4 Isolation of MSCs En Masse 5 Evaluation of Gene Function by MC-Specific Gene Manipulation . 6 6 Induction of Quiescent MSCs Requires Multiple Steps 7 7 A Working Hypothesis for the Induction of Quiescent MSCs 8 8 Induction of Quiescent MSCs In Vitro Future Direction 10 Abstract. An important issue in cancer therapy...

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2005b Lee et al. 2004 Taniguchi et al. 2005 . Therefore, forced expression of Wnt antagonists or recombinant antagonist proteins may be a promising therapeutic strategy. For example, transfection of SFRP gene constructs into various types of cancer cell lines lacking SFRP expression induced apoptosis and cell growth suppression He et al. 2005b Horvath et al. 2004 Lee et al. 2004 Roth et al. 2000 Suzuki et al. 2004 Zi et al. 2005 . In addition, restored WIF-1 expression also led to decreased...