Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0029463 (osteosarcoma)
 16,637 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Adrenomedullin (ADM), a multifunctional regulatory peptide, is potentially induced by hypoxia in physiological and pathological tissues, including many types of malignant tumors. Recent research has demonstrated that ADM expression is highly associated with the prognosis and disease severity of human osteosarcoma. However, the effect of ADM on the apoptosis of osteosarcoma cells and its possible mechanism remain to be elucidated. In the present study, we observed that mRNA and protein levels of ADM were increased in human osteosarcoma SOSP-F5M2 cells under a hypoxic microenvironment induced by cobalt chloride (CoCl2) in a time-dependent manner. Treatment with ADM significantly blunted hypoxic-induced apoptosis, evaluated by Hoechst 33342 staining and Annexin V-FITC/PI labeling. The expression of B-cell lymphoma-2 (Bcl-2) was increased by administration of ADM; meanwhile, this effect was reversed by exogenously adding U0126, a selective inhibitor of MEK or ADM22-52 (ADM-specific receptor antagonist). These results demonstrated that ADM acted as a survival factor to inhibit hypoxic-induced apoptosis via interacting with its receptors CRLR-RAMP (2,3) in osteosarcoma cells. The anti-apoptotic function of ADM was found to be mediated by upregulation of the expression of Bcl-2 partially through activation of the MEK/ERK1/2 signaling pathway. Therefore, targeting of the ADM/ADM acceptors/ERK1/2/Bcl-2 pathway may provide a potential strategy through which to induce the apoptosis of osteosarcoma cells.
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PMID:Hypoxia-induced apoptosis is blocked by adrenomedullin via upregulation of Bcl-2 in human osteosarcoma cells. 2603 96

BACKGROUND Oxycodone is a semisynthetic opioid receptor agonist, and is frequently used for pain control in patients with cancer. Most oxycodone is metabolized by N-demethylation to noroxycodone by CYP3A. Rifampin is a strong inducer of several drug-metabolizing enzymes, including CYP3A. Hence, rifampin-induced CYP3A activity may decrease the effect of oxycodone. CASE REPORT Osteosarcoma is a highly aggressive primary bone tumor of childhood and adolescence. Here, we report a 30-year-old male with osteosarcoma of the femur with lung metastases in the upper lobe. The lung also contained small, scattered nodular lesions that were identified as tuberculosis. Multi-drug therapy, including rifampin, was administered. The upper-lobe metastatic lesion extended to the brachial plexus and caused severe pain. Over 1000 mg per day of oxycodone was ineffective for pain control. However, morphine was able to control his pain at about one-third the equivalent dose. CONCLUSIONS Our patient demonstrated oxycodone resistance due to rifampin. Chemotherapy may have compromised the patient's immune system, thus theoretically increasing the risk of tuberculosis. Recognition of the interactions between rifampin and oxycodone is important in this and other cancers. Notably, for patients using high doses of oxycodone to manage severe pain, stopping rifampin may lead to oxycodone overdose.
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PMID:Oxycodone Resistance Due to Rifampin Use in an Osteosarcoma Patient with Tuberculosis. 2906 56