Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0178874 (tumor progression)
 40,807 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hypercalcemia is the most common paraneoplastic syndrome associated with cancer. This paper addresses the etiology and pathogenesis of hypercalcemia of malignancy and discusses the relative contributions of local and humoral effects on bone and renal calcium homeostasis. The roles of parathyroid hormone-related protein and other osteolytic cytokines are outlined. New biochemical markers that enable more specific monitoring of the response of bone metastases to treatment are introduced, including urinary excretion of the collagen crosslinks pyridinoline and deoxypyridinoline. The clinical management and prevention of hypercalcemia is systemically outlined, including indications for bisphosphonate, glucocorticoid, and calcitonin therapy. The results of recent trials of bisphosphonate therapy for the prevention of tumor progression and its subsequent problems such as bone pain, fracture, and hypercalcemia also are discussed.
 ...
PMID:Hypercalcemia and bone resorption in malignancy. 763 18

The extracellular calcium-sensing receptor (CaR) is a versatile sensor of small, polycationic molecules ranging from Ca2+ and Mg2+ through polyarginine, spermine, and neomycin. The sensitivity of the CaR to changes in extracellular Ca2+ over the range of 0.05-5 mM positions the CaR as a key mediator of cellular responses to physiologically relevant changes in extracellular Ca2+. For many cell types, including intestinal epithelial cells, breast epithelial cells, keratinocytes, and ovarian surface epithelial cells, changes in extracellular Ca2+ concentration over this range can switch the cellular behaviour from proliferation to terminal differentiation or quiescence. As cancer is predominantly a disease of disordered balance between proliferation, differentiation, and apoptosis, disruptions in the function of the CaR could contribute to the progression of neoplastic disease. Loss of the growth suppressing effects of elevated extracellular Ca2+ have been demonstrated in parathyroid hyperplasias and in colon carcinoma, and have been correlated with changes in the level of CaR expression. Activation of the CaR has also been linked to increased expression and secretion of PTHrP (parathyroid hormone-related peptide), a primary causal factor in hypercalcemia of malignancy and a contributor to metastatic processes involving bone. Although mutation of the CaR does not appear to be an early event in carcinogenesis, loss or upregulation of normal CaR function can contribute to several aspects of neoplastic progression, so that therapeutic strategies directed at the CaR could potentially serve a supportive function in cancer management.
 ...
PMID:The role of the calcium-sensing receptor in cancer. 1520 Jan 53

Bone is the most common site of metastasis for breast cancer. Bone metastasis significantly affects both quality of life and survival of the breast cancer patient. Clinically, complications secondary to bone metastasis include pain, pathologic fractures, spinal cord compression, and hypercalcemia of malignancy. Because bone metastasis is extremely common in patients with metastatic breast cancer, clinical management of bone metastases is an important and challenging aspect of treatment in the metastatic setting.The skeleton is a metabolically active organ system that undergoes continuous remodeling throughout life. A delicate balance of the bone-forming osteoblasts and bone-resorbing osteoclasts in the dynamic microenvironment of the skeleton maintains normal bone remodeling and integrity. The presence of metastatic lesions in bone disrupts the normal bone microenvironment and upsets the fine balance between the key components. The changes in the bone microenvironment then create a vicious cycle that further promotes bone destruction and tumor progression.Various therapeutic options are available for bone metastases of breast cancer. Treatment can be tailored for each patient and, often requires multiple therapeutic interventions. Commonly used modalities include local therapies such as surgery, radiation therapy and radiofrequency ablation (RFA) together with systemic therapies such as endocrine therapy, chemotherapy, monoclonal antibody-based therapy, bone-enhancing therapy and radioisotope therapy. Despite the use of various therapeutic modalities, bone metastases eventually become resistant to therapy, and disease progresses.In this chapter, we describe the clinical picture and biological mechanism of bone metastases in breast cancer. We also discuss known risk factors as well as detection and assessment of bone metastases. We present therapeutic options for bone metastasis using a multidisciplinary approach. Further, we describe future directions for bone metastasis management, focusing on novel bone-specific targeted therapies.
 ...
PMID:Bone Metastasis of Breast Cancer. 3145 82