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Metastases rather than primary tumors are responsible for the lion’s share of the morbidity and mortality arising from malignant disease. Patients with advanced breast or prostate cancers usually develop bone metastases and usually harbor the bulk of their tumor burden in the bone at the time of death. Although it is difficult to quantify the prevalence of bone metastases, natural history and autopsy...
Parathyroid hormone-related peptide (PTHrP) was originally isolated as a causal factor for hypercalcemia of malignancy (HM), one of the most frequent paraneoplastic syndromes. The association of hypercalcemia with malignancy was originally assumed to be the result of tumor invasion of bone with resultant osteolysis (1,2), but subsequent studies demonstrated an association of hypercalcemia with cancer,...
Vitamin D is a pro-hormone with a wide variety of biological actions once converted to its biologically active compound 1,25-dihydroxyvitamin D3 [1,25(OH)2D3]. Its classical effect in the prevention and treatment of rickets has been known for over a century (1). More recently, nonclassical actions of vitamin D have been recognized and, in particular, its potent action on the proliferation and differentiation...
Metastatic disease contributes to a large proportion of cancer-related deaths, and bone is among the most common sites for metastases for tumors originating in the breast and prostate. The propensity for these cancers to form bone metastases is not completely understood; however, it undoubtedly involves a number of unique characteristics of both the tumor cells and the bone microenvironment. Such...
Death from prostate cancer is usually attributable to the development of bone and visceral organ metastases. The spine, pelvic bones, and ribs are among the most frequent sites of prostate cancer bone metastases. The peripheral skeleton and skull are less frequent sites (1,2). There are two hypotheses for the preferential homing of prostate cancer cells to bone. The first is that the mechanical hemodynamics...
A considerable amount of clinical and experimental data has shown that proteolytic enzymes affecting the composition and function of the extracellular matrix (ECM) and cell surface molecules appear to be essential for the metastatic process. Certain structural changes of the ECM accompany cell migration during physiological tissue remodeling and tumor cell invasion. The ECM forms basement membranes...
Metastasis is the spread of cancer cells from a primary site, resulting in the establishment of secondary tumors in distant locations (1–3). Certain types of cancer have organ-specific preferences for metastatic growth, and breast and prostate cancers often preferentially metastasize to bone (2,3). In fact, it has been estimated that the majority of breast and prostate cancer patients who succumb...
Interleukin (IL)-11 is a pleiotropic cytokine that belongs to the IL-6 family of cytokines (1). Other cytokines belonging to this family include oncostatin M (OSM), leukemia inhibitory factor (LIF), cardiotrophin (CT)-1, and ciliary neurotrophic factor (CNTF). All members of this cytokine family have their own unique α-chain receptors, which, when occupied, initiate signal transduction via the recruitment...
When tumors progress to greater malignancy, cells within the tumor develop an increasing ability to detach from neighboring cells and invade through surrounding tissues and tissue boundaries to form new growths (metastasis) at sites distinct from that of the primary tumor. The molecular mechanisms involved in the metastatic process are diverse and not completely understood; however, the processes...
Originally discovered as a product of cancers that produce hypercalcemia, parathyroid hormone-related protein (PTHrP) has been demonstrated to be a product of many malignant tissues, including prostate and lung cancer, where it can regulate growth and proliferation in vivo and in vitro (1–8). The amino-terminus of PTHrP reacts with the PTH/PTHrP receptor (PTHrPR) and produces most of the biological...
Metastasis of cancer cells from a primary site involves a sequence of events, including the extravasation of the tumor cells into circulation and the interactions with platelets and other components of the hemostatic system (1,2). These interactions, in turn, result in the adhesion and penetration of these metastatic cells and subsequent intravasation into the tissue. Several studies demonstrated...
Patients with bone metastases are at risk for a variety of skeletal complications (1), each of which can lead to a significant reduction in patient quality of life and considerable expense to the health care system. Skeletal complications are multifactorial in nature and typically include vertebral fractures, nonvertebral fractures, spinal cord compression, episodes of bone pain requiring radiation...
Metastasis to bone is a major complication of advanced cancer and occurs in more than 400,000 cancer patients each year. Bone metastasis can arise from many different tumor types, including breast, prostate, lung, renal cell, thyroid, and bladder cancer, and in patients with melanoma and myeloma. The development of bone metastasis in cancer patients contributes significantly to the morbidity and mortality...
Bone metastasis commonly occurs in association with solid malignant tumors such as breast, prostate, lung, and renal cancers (1–5). Thirty to seventy percent of cancer patients have skeletal metastasis (6), making the axial skeleton the third most common site for metastasis after lung and liver. Because all of these cancers (breast, prostate, lung, and renal) are common, metastatic bone lesions actually...
Cancer spread to bone is a significant cause of morbidity in patients with metastatic spread. Metastatic bone disease is also the most common cause of destructive lesions in the adult skeleton. With improvements in adjuvant therapies and a decline in age-standardized cancer mortality, skeletal metastases are increasingly prevalent in advanced spread (1). As such, there will be greater emphasis on...
Although strides have been made in the diagnosis and treatment of cancer in the past few decades, advanced, metastatic cancer remains extremely difficult to treat. Obviously, a major hurdle in improving survival is the treatment or prevention of metastatic disease, either to eliminate it completely or to contain it like other chronic diseases. To reach the metastatic stage, the cancer cells undergo...
Tetracyclines are a class of related antibiotic compounds first discovered by retired American botanist Benjamin Duggar (1) in the late 1940s. Duggar extracted a yellowish crystalline compound with unique antibacterial properties, called aureomycin (7-chlortetracycline), from soil found near cemeteries containing Streptomyces aureofaciens, a fungallike bacteria of the Actinomycetales order. The parent...
The clinical usefulness of bisphosphonates lie in their ability to inhibit bone resorption, which underlies various pathological conditions ranging from osteoporosis and Paget’s disease to hypercalcemia of malignancy and complications associated with cancer metastasis to bone.
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