Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0153690 (bone metastases)
 6,382 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Bisphosphonates are endogenous pyrophosphate analogs in which a carbon atom replaces the central atom of oxygen. They are indicated in non-neoplastic diseases including osteoporosis, corticosteroid-induced bone loss, Paget disease, and in cancer-related diseases such as neoplastic hypercalcemia, multiple myeloma and bone metastases secondary to breast and prostate cancer. There is now extensive in vitro evidence suggesting a direct antitumor effect of bisphosphonates at different levels of action. Some new in vitro and in vivo studies support the cytostatic effects of bisphosphonates on tumor cells, and the effects on the regulation of cell growth, apoptosis, angiogenesis, cell adhesion, and invasion, with particular attention to biological properties. Well designed clinical trials are necessary to investigate whether the antitumor potential of bisphosphonates may be clinically relevant. On the basis of their effects on macrophages, we may divide bisphosphonates into two distinct categories: aminobisphosphonates, which sensitize macrophages to an inflammatory stimulus inducing an acute-phase response, and non-aminobisphosphonates that can be metabolized into macrophages and that may inhibit the inflammatory response of macrophages. There is evidence of aminobisphosphonate-induced pro-inflammatory response, in particular, related to modifications of the cytokine network. Several in vivo studies have demonstrated an acute-phase reaction after the first administration of aminobisphosphonates, with a significant increase in the main pro-inflammatory cytokines. However, a peculiar aspect concerning the action of non-aminobisphosphonates seems to be an anti-inflammatory activity caused by the inhibition of the release of inflammatory mediators from activated macrophages, such as interleukin (IL)-6, tumor necrosis factor-alpha and IL-1. The inhibition of inflammatory responses is demonstrated in both in vivo and in vitro models. This activity suggests the use of non-aminobisphosphonates in several inflammatory diseases characterized by macrophage-mediated production of acute-phase cytokines, as prevention of erosions in rheumatoid arthritis, and of loosening of joint prostheses, as well as possibly in osteoarthritis, ankylosing spondylitis, myelofibrosis, and hypertrophic pulmonary osteoarthropathy.
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PMID:Bisphosphonate effects in cancer and inflammatory diseases: in vitro and in vivo modulation of cytokine activities. 1524 2

Pulmonary inflammatory myofibroblastic tumors (PIMTs) are extremely rare in adults. If occurring in patients >40 years old, PIMT should be rapidly distinguished from lung cancer. The present study aimed to characterize the imaging features of PIMT in patients >40 years old in order to improve the diagnosis of PIMT. The imaging data of 10 patients with PIMT were reviewed retrospectively. Of the patients, eight underwent computed tomography (CT), two underwent positron emission tomography (PET)/CT and four underwent single-photon emission computed tomography (SPECT). Unenhanced CT revealed 10 lesions with a maximum diameter ranging between 5 and 57 mm located in the lower (n=6) or upper (n=4) lobe, in a peripheral (n=9) or central (n=1) region, and that were well- (n=4) or ill-defined (n=6), and round to oval (n=5) or irregular (n=5) in shape. Calcification (n=3), necrosis (n=6), cavity (n=4), air bronchogram (n=6) and obstructive pneumonia (n=1) were also observed in the patients. Contrast-enhanced CT revealed six lesions with moderate to high contrast enhancement in the arterial and venous phases, including four lesions with delayed enhancement. PET/CT identified two lesions with increased tracer uptake that were homogeneous and heterogeneous and each exhibited a maximal standard uptake value (SUVmax) of 6.0 and 5.4, respectively. The delayed PET/CT revealed foci that each exhibited an increased SUVmax of 6.9 and 5.9, respectively. SPECT demonstrated no definitive bone metastases, but did reveal atypical hypertrophic pulmonary osteoarthropathy in one patient. The combined imaging methods may lead to a more precise evaluation of PIMT in patients >40 years old.
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PMID:Imaging observations of pulmonary inflammatory myofibroblastic tumors in patients over 40 years old. 2578 60