Advances in Adjuvant Therapy: Potential for Prognostic and Predictive Biomarkers
Melanoma is the third most common skin cancer but accounts for the majority of skin cancer-related mortality. The rapidly rising incidence and younger age at diagnosis has made melanoma a leading cause of lost productive years of life and has increased the urgency of finding improved adjuvant therapy for melanoma. Interferon-α was approved for the adjuvant treatment of resected high-risk melanoma following studies that demonstrated improvements in relapse-free survival and overall survival that were commenced nearly 30 years ago. The clinical benefits associated with this agent have been consistently observed across ...
Source: Springer protocols feed by Cancer Research - November 27, 2013 Category: Cancer & Oncology Source Type: news

Detecting Mechanisms of Acquired BRAF Inhibitor Resistance in Melanoma
V600BRAF mutation was identified as an ideal target for clinical therapy due to its indispensable roles in supporting melanoma initiation and progression. Despite the fact that BRAF inhibitors (BRAFi) can elicit anti-tumor responses in the majority of treated patients and confer overall survival benefits, acquired drug resistance is a formidable obstacle to long-term management of the disease. Several aberrant events including RTK upregulation, NRAS mutation, mutant BRAF amplification or alternative splicing, and MEK mutation have been reported as acquired BRAFi resistance mechanisms. Clinially, detection of these resistan...
Source: Springer protocols feed by Cancer Research - November 27, 2013 Category: Cancer & Oncology Source Type: news

Integrating Molecular Biomarkers into Current Clinical Management in Melanoma
Personalized melanoma medicine has progressed from histopathologic features to serum markers to molecular profiles. Since the identification of activating BRAF mutations and subsequent development of drugs targeting the mutant BRAF protein, oncologists now need to incorporate prognostic and predictive biomarkers into treatment decisions for their melanoma patients. Examples include subgrouping patients by genotype profiles for targeted therapy and the development of serologic, immunohistochemical, and genotype profiles for the selection of patients for immunotherapies. In this chapter, we provide an overview of the current...
Source: Springer protocols feed by Cancer Research - November 27, 2013 Category: Cancer & Oncology Source Type: news

Emerging Clinical Issues in Melanoma in the Molecularly Targeted Era
The standard of care of patients with malignant melanoma is dramatically changing, hallmarked by the approval of three new agents for the treatment of malignant melanoma in 2011. In this changing therapeutic landscape, several clinical issues are emerging which will best be addressed through the application of advances in molecular analytics, diagnostics, and therapeutics. It is expected that dedicated and coordinated efforts in basic, translational, and clinical will be responsible for the next major breakthroughs in the care of patients with this dreaded disease. In this chapter, five critical, emerging clinical issues a...
Source: Springer protocols feed by Cancer Research - November 27, 2013 Category: Cancer & Oncology Source Type: news

Novel Insights/Translational Implication from the Emerging Biology of Melanoma
Melanoma is a main example of how applying advances in basic biology, pharmacology, and molecular diagnostics into the clinic results in unprecedented benefits to patients. After many years of lack of advances in the treatment of patients with metastatic melanoma, the advent of new therapies that block driver oncogenic signaling and modulate immune responses to cancer provided the first studies with a positive impact in overall survival (OS) of patients with advanced melanoma. The pace of progress in the treatment of this disease has been greatly accelerated by these initial breakthroughs, and it continues with new generat...
Source: Springer protocols feed by Cancer Research - November 27, 2013 Category: Cancer & Oncology Source Type: news

Theoretical Considerations in Using Animal Models of Metastasis and Brief Methodology for In Vivo Colorectal Cancer Models in SCID and Nude Mice
Metastatic spread is generally responsible for the mortality of colorectal cancer patients. There are no adequate treatments for advanced colorectal cancer, and novel therapeutic modalities are urgently required. To this end, valid metastatic models, which accurately mimic the disease process, are needed. When deciding upon a metastasis model, the goals of the investigation will dictate the complexity of the model chosen. If biological mechanisms are being investigated, only a small number of experimental animals may be required, and a more complex, surgically intensive model may be used. If a therapeutic agent is being ev...
Source: Springer protocols feed by Cancer Research - October 8, 2013 Category: Cancer & Oncology Source Type: news

Computer Simulation of the Metastatic Progression
A novel computer model based on a discrete event simulation procedure describes quantitatively the processes underlying the metastatic cascade. Analytical functions describe the size of the primary tumor and the metastases, while a rate function models the intravasation events of the primary tumor and metastases. Events describe the behavior of the malignant cells until the formation of new metastases. The results of the computer simulations are in quantitative agreement with clinical data determined from a patient with hepatocellular carcinoma in the liver. The model provides a more detailed view on the process than a con...
Source: Springer protocols feed by Cancer Research - October 8, 2013 Category: Cancer & Oncology Source Type: news

Chick Heart Invasion Assay
Tumors are microecosystems in which a continuous cross talk between cancer cells and host cells decides on the invasive behavior of the tumor cell population as a whole (Mareel et al., Encyclopedia of cancer, San Diego, CA, Academic Press, 1997). Both compartments secrete activating and inhibitory factors that modulate activities such as cell–extracellular matrix (ECM) interaction, cell–cell adhesion, remodeling of the ECM, and cell motility. For this reason, confrontations of cancer cells with a living normal host tissue in organ culture have been introduced by several groups: Wolff and Schneider in France (Wo...
Source: Springer protocols feed by Cancer Research - October 8, 2013 Category: Cancer & Oncology Source Type: news

Cell Aggregation Assays
Invasion of carcinoma cells is the result of a disequilibrium between invasion promoter and invasion suppressor gene products (Mareel and Van Roy, Anticancer Res 6:419–435, 1986). The E-cadherin/catenin complex is the most potent invasion suppressor at the cell membrane of epithelioid cells (Duffy et al., J Pathol 214:283–293, 2008). This complex consists of E-cadherin, a transmembrane glycoprotein of 120 kDa, which is linked to the actin cytoskeleton via the catenins (Behrens et al., J Cell Biol 108:2435–2447, 1989). Downregulation of the complex is a common feature in invasive carcinoma cells, and has b...
Source: Springer protocols feed by Cancer Research - October 8, 2013 Category: Cancer & Oncology Source Type: news

Adhesion of Tumor Cells to Matrices and Endothelium
Adhesion of tumor cells to matrix components and endothelial cells is essential for tumor metastasis. Investigation of the adhesion molecules required and the signals which induce tumor cell adhesion and migration are crucial in order to increase our understanding of this process. This chapter describes protocols which may be used to study tumor cell adhesion to purified matrix elements and tissue sections. It also details methods used to investigate cell adhesion to endothelial cells, both under static and flow conditions. In addition, there is a section detailing the use of endothelial cell cultures on three-dimensional ...
Source: Springer protocols feed by Cancer Research - October 8, 2013 Category: Cancer & Oncology Source Type: news

Small-Cell Lung Cancer (SCLC) Cell Adhesion on E- and P-Selectin Under Physiological Flow Conditions
Hematogenous metastasis is still a poorly understood phenomenon. The rate-limiting step within the metastatic cascade is not yet clear although it may be estimated that the extravasation of circulating tumor cells is a step of crucial importance, as most tumor cells that are shed into circulation undergo apoptosis. The process of extravasation includes a cascade of consecutive steps, starting with adhesion of tumor cells circulating in the bloodstream to endothelial cells, mimicking leukocyte adhesion and transmigration. Endothelial cell selectin–leukocyte glycan interaction occurs when leukocytes adhere to endotheli...
Source: Springer protocols feed by Cancer Research - October 8, 2013 Category: Cancer & Oncology Source Type: news

Rocking Adhesion Assay System to Study Adhesion and Transendothelial Migration of Cancer Cells
Adhesion of metastatic cancer cells to the vascular endothelium of the target organs and their subsequent transendothelial migration is one of the critical, yet poorly understood, steps of the metastatic cascade. Conventionally, the mechanisms of this complex process have been studied using static adhesion systems or flow assay systems. Static assay systems are easy to set up and perform but do not mimic the physiological conditions of blood flow. Flow assays closely mimic physiological conditions of flow but are time consuming and require specialist equipment. In this chapter we describe the rocking adhesion system which ...
Source: Springer protocols feed by Cancer Research - October 8, 2013 Category: Cancer & Oncology Source Type: news

Single Cell and Spheroid Collagen Type I Invasion Assay
Tumor invasion is the outcome of a complex interplay between cancer cells and the stromal environment and requires the infiltration of a dense, cross-linked meshwork of collagen type I extracellular matrix. We use a membrane-free single-cell and spheroid-based complementary model to study cancer invasion through native collagen type I matrices. Cell morphology is preserved during the assays allowing real-time monitoring of invasion-induced changes in cell structure and F-actin organization. Combination of these models with computerized quantification permits the calculation of highly reproducible and operator-independent d...
Source: Springer protocols feed by Cancer Research - October 8, 2013 Category: Cancer & Oncology Source Type: news

In Vitro Invasion Assay Using Matrigel™: A Reconstituted Basement Membrane Preparation
Basement membranes, specialized extracellular matrices composed of collagens, laminins, and proteoglycans, form thin, continuous sheetlike structures that separate epithelial tissues from adjacent connective tissues. The crossing of basement membranes by cancer cells is a crucial aspect of metastasis—it must occur in order that cancer cells can invade lymphatic or blood vessels during dissemination and also when they penetrate into the target organ tissue where they will eventually colonize to form secondary tumors. The assay system described in this chapter utilizes the solubilized basement membrane preparation Matr...
Source: Springer protocols feed by Cancer Research - October 8, 2013 Category: Cancer & Oncology Source Type: news

Identifying the Origin and Phenotype of Cells in Tumor Xenografts
The growth of human tumor cells transplanted into immunodeficient mice is frequently studied to gain understanding about the way potential drug treatments interfere with growth in vivo. A wide range of methods is available for learning about specific aspects of tumor cell behavior, for example, cells may be administered to follow their ability to grow close to the site of injection which may be at a generic site or one specific to that type of tumor. Some models of metastasis follow the appearance of a tumor mass after intravascular administration of tumor cells; others score remote growth after removal of a primary tumor ...
Source: Springer protocols feed by Cancer Research - October 8, 2013 Category: Cancer & Oncology Source Type: news