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

Bone metastases of breast cancers produce not only osteolytic but also osteosclerotic lesions. The latter are often observed after androgenic treatment of the tumor. Potential production of osteoblast stimulating activity (ObSA) in breast cancer cell lines, and possible androgen control of this activity have been investigated. Conditioned media (CM) collected from 4 breast cancer cell lines (MCF-7, ZR75, MDA-MB 231, BT20) was tested in vitro on ROS 17/2,8 osteoblast-like cells and on osteoblasts derived from human bone biopsies. The parameters monitored in osteoblasts were [3H]thymidine incorporation, alkaline phosphatase activity, and osteocalcin secretion. Serum-free media conditioned during 24 h by MCF-7 cells presented the highest ObSA. CM decreased thymidine incorporation in DNA and increased alkaline phosphatase activity in a dose-dependent manner. Bone GLA protein (osteocalcin) secretion by human osteoblasts was not increased however in the presence of CM. MCF-7 cells were cultured in the presence of dihydrotestosterone (DHT) [1-100 nM] for 5 days. Serum-free, DHT-free CM collected after an additional 24 h, contained alkaline-phosphatase stimulating activity which was DHT dose-dependent. Estradiol and 1,25(OH)2D3 failed to elicit a comparable increase of the ObSA in the CM. In conclusion, MCF-7 cells product factor(s) that interfere with bone remodeling. The DHT modulation of ObSA parallels the estradiol control of MCF-7 cells osteolytic lesions in relation with Prostaglandin E secretion. Sex hormones at physiological and pharmacological levels might thus control both osteosclerotic and osteolytic lesions observed in bone deposits of hormone dependent cancers.
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PMID:Androgens increase osteoblast-stimulating activity of human breast cancer cells in vitro. 370 24

Bone sialoprotein (BSP) is a major noncollagenous protein of the mineralized bone extracellular matrix that has been implicated in the nucleation of hydroxyapatite. Recent studies have shown that BSP is also expressed by osteotropic cancers suggesting BSP might play a role in the pathogenesis of bone metastases. The present study investigates regulation of BSP transcription in rat osteosarcoma ROS 17/2.8 cells by flavonoids: genistein (an inhibitor of protein tyrosine kinases), daidzein (an inactive compound of genistein), flavone, and flavanone. Genistein, daidzein, and flavone (50 microM) increased steady state levels of BSP mRNA about 1.7-fold at 12 h. From transient transfection assays using various sized BSP promoter-luciferase constructs, genistein increased luciferase activities within 12 h. Constructs including the promoter sequence nucleotides (nts) -116 to -43 (pLUC3) were found to enhance transcriptional activity approximately 2.6-fold in ROS 17/2.8 cells treated with genistein (50 microM). Daidzein, flavone, and flavanone (50 microM) also increased luciferase activities. In contrast, the tyrosine kinase inhibitors, herbimycin A and lavendustin A, which do not have a flavonoid structure, did not stimulate BSP transcription. Transcriptional stimulation by genistein was almost completely abrogated in a construct that included 2 bp mutations in the inverted CCAAT box. A monoclonal antibody against NF-YA, a CCAAT box-binding transcription factor, inhibited formation of DNA-NF-Y protein complex in gel shift assays formed by nuclear extracts of ROS 17/2.8 cells. These data suggest that the inverted CCAAT box is required for flavonoid-induced BSP expression and that the stimulatory action is dependent on the flavone structure and does not involve an inhibitory action on protein tyrosine kinase.
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PMID:Activation of bone sialoprotein gene transcription by flavonoids is mediated through an inverted CCAAT box in ROS 17/2.8 cells. 1211 14

Rearranged during transfection proto-oncogene (RET) fusions represent a potentially targetable oncogenic driver in non-small cell lung cancer (NSCLC). Imaging features and metastatic patterns of advanced RET fusion-positive (RET+) NSCLC are not well established. Our goal was to compare the imaging features and patterns of metastases in RET+, ALK+ and ROS1+ NSCLC. Patients with RET+, ALK+, or ROS1+ NSCLC seen at our institution between January 2014 and December 2018 with available pre-treatment imaging were identified. The clinicopathologic features, imaging characteristics, and the distribution of metastases were reviewed and compared. We identified 215 patients with NSCLC harboring RET, ALK, or ROS1 gene fusion (RET = 32; ALK = 116; ROS1 = 67). Patients with RET+ NSCLC were older at presentation compared to ALK+ and ROS1+ patients (median age: RET = 64 years; ALK = 51 years, p < 0.001; ROS = 54 years, p = 0.042) and had a higher frequency of neuroendocrine histology (RET = 12%; ALK = 2%, p = 0.025; ROS1 = 0%, p = 0.010). Primary tumors in RET+ patients were more likely to be peripheral (RET = 69%; ALK = 47%, p = 0.029; ROS1 = 36%, p = 0.003), whereas lobar location, size, and density were comparable across the three groups. RET+ NSCLC was associated with a higher frequency of brain metastases at diagnosis compared to ROS1+ NSCLC (RET = 32%, ROS1 = 10%; p = 0.039. Metastatic patterns were otherwise similar across the three molecular subgroups, with high incidences of lymphangitic carcinomatosis, pleural metastases, and sclerotic bone metastases. RET+ NSCLC shares several distinct radiologic features and metastatic spread with ALK+ and ROS1+ NSCLC. These features may suggest the presence of RET fusions and help identify patients who may benefit from further molecular genotyping.
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PMID:Imaging Features and Patterns of Metastasis in Non-Small Cell Lung Cancer with RET Rearrangements. 3218 22