Metastases

Metastasis Metastasis is the spread of a disease (usually cancer) from an original site of infection to other parts of the body. This usually happens when cancer cells break off from the original tumor and travel through the blood vessels to a new site. This kind of cancer is called malignant, meaning that it is life-threatening and usually fatal. 

Antineoplastic agents that cannot be grouped under subheadings 1-9 include miltefosine which is an alkylphosphocholine that is used to treat skin metastasis of breast cancer, and crispantase which breaks down asparagine to aspartic acid and ammonia. It is active against tumor cells that lack the enzyme asparaginase, such as acute lymphoblastic leukemia cells. Side effects include irritation of the skin in the case of miltefosine and anaphylactic reactions in the case of crispantase. Another recent development is the proteasome inhibitor bortezomib which is used to treat multiple myeloma. 

Bisphosphonates have been shown to be highly effective in osteoporosis, cancer bone metastasis, multiple myeloma, and Paget s disease of bone. While generally very well tolerated, these drugs do have potential adverse effects. Recently, the association of long-term high dose bisphosphonate treatment with osteonecrosis of the jaw has been described. This is a potentially serious side effect seen mostly in patients with multiple myeloma or... 

In malignant prostate epithelial cells, auto- and paracrine release of ET-1 is a critical factor in ETA receptor-mediated proliferation [5]. In addition, the ET-1/ETa receptor axis has emerged as a potential target in prostate cancer bone metastasis... 

Ras is a G protein that cycle between two conformations, an activated Ras-GTP or inactivated form Ras-GDP. Ras, attached to the cell membrane by lipidation, is a key component in many signalling cascades, which couple growth factor receptors to downstream effectors that control such processes as cytoskeletal integrity, proliferation, cell adhesion, apoptosis and cell migration. Mutations and dysregulations of the Ras protein leading to increased invasion and metastasis, and decreased apoptosis are very common in cancers. 

Stein U, Arlt F, Walther W et al (2006) The metastasis-associated gene S100A4 is a novel target of p-catenin/ T-cell factor signaling in colon cancer. Gastroenterology 131 1486-1500... 

Furthermore, peptidomimetic SH2 domain inhibitors for Src, such as AP-22408 have been designed that interfere with effector binding and thereby disrupt signal transduction. AP-22408 decreases bone resorption in animal studies and may be a promising drug to treat osteoporosis and other bone diseases, such as Paget s disease and osteolytic bone metastasis. 

Several other inhibitors of nonreceptor PTKs are currently in development but only a few of them are studied in clinical trials. Noteworthy, Dasatinib does not only inhibit c-Abl, but also potently blocks Src activity, a property that may contribute to its beneficial clinical effects in CML. Other kinase inhibitors being developed that inhibit c-Abl and/or Src are AZD-0530, AP-23994, PD-0183805, SU-6656, and Bosutinib (SKI-606). Furthermore, peptidomimetic SH2 domain inhibitors for Src, such as AP-22408 have been designed that decrease bone resorption and may be promising drugs to treat osteoporosis and other bone diseases, such as Paget s disease and osteolytic bone metastasis. 

The estrogens are used cautiously in patients with gallbladder disease, hypercalcemia (may lead to severe hypercalcemia in patients with breast cancer and bone metastasis), cardiovascular disease, and liver impairment. 

The Role of Myosins in Cell Locomotion The Role of Actin-Binding Proteins in Cell Locomotion The Transduction of Extracellular Motility Signals to the Cytoskeleton Lipid Flow and Cell Locomotion The Role of Cell Locomotion in Metastasis Intracellular Motility Microtubule-Based Intracellular Motility... 

A factor known as scatter factor has been characterized which causes the break up and stimulates motility of epithelial cell clumps (Stoker et al., 1987). This factor is identical to hepatocyte growth factor and increases the rate of locomotion of several other cell types. Motility factors elaborated from tumor cells are considered to play an important role in metastasis (see later). Guidance of cells by the physical topography of the substratum is another factor that profoundly affects the behavior of cells. 

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