rifampin and Bone-Neoplasms

To investigate induction of cell death in Osteosarcoma (OS) using the anti-tuberculosis drug, rifampicin, loaded into exosomes.. BMSC-exosomes were isolated by ultracentrifugation and loaded ultrasonically with rifampicin. Nanoparticle exosome-rifampicin (EXO-RIF) was added to the OS cell-lines, 143B and MG63, in vitro, to observe the growth inhibitory effect. In vivo experiments were conducted by injecting fluorescently labeled EXO-RIF through the tail vein of 143B cell xenograft nude mice and tracking distribution. Therapeutic and toxic side-effects were analyzed systemically.. Sonication resulted in encapsulation of rifampicin into exosomes. Exosome treatment accelerated the entry of rifampicin into OS cells and enhanced the actions of rifampicin in inhibiting OS proliferation, migration and invasion. Cell cycle arrest at the G2/M phase was observed. Dynamin-related protein 1 (Drp1) was activated by EXO-RIF and caused mitochondrial lysis and apoptosis. Exosome treatment targeted rifampicin to the site of OS, causing OS apoptosis and improving mouse survival in vivo.. The potent Drp1 agonist, rifampicin, induced OS apoptosis and exosome loading, improving OS targeting and mouse survival rates. EXO-RIF is a promising strategy for the treatment of diverse malignancies.

Topics: Animals; Apoptosis; Bone Neoplasms; Dynamins; Exosomes; Humans; Mice; Mice, Nude; Nanoparticles; Osteosarcoma; Rifampin

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.

Topics: Adult; Analgesics, Opioid; Antibiotics, Antitubercular; Bone Neoplasms; Cancer Pain; Drug Resistance; Humans; Lung Neoplasms; Male; Osteosarcoma; Oxycodone; Rifampin; Tuberculosis, Pulmonary

Topics: Antitubercular Agents; Aza Compounds; Bone Neoplasms; Diagnosis, Differential; Drug Therapy, Combination; Ethambutol; Fluorodeoxyglucose F18; Fluoroquinolones; Humans; Lung; Magnetic Resonance Imaging; Male; Middle Aged; Moxifloxacin; Osteomyelitis; Positron-Emission Tomography; Quinolines; Radiopharmaceuticals; Rifampin; Spine; Tomography, X-Ray Computed; Tuberculosis, Osteoarticular

The effect of the proinflammatory cytokine interleukin (IL)-1beta on the cellular proliferation of human osteoblastic cells (SaM-1) and osteosarcoma-derived cells (SaOS-2, HOS, and MG-63) was examined. IL-1beta stimulated the proliferation of SaM-1 and MG-63 cells, but had no effect on that of SaOS-2 or HOS cells. Using reverse transcription-polymerase chain reaction (RT-PCR) analysis, the mRNA expression of IL-1 receptor type I (IL-1R1) was detected in SaM-1 and MG-63 cells consistently, but not in SaOS-2 or HOS cells in the proliferative stage. Neither the decoy inhibitory IL-1 receptor type II (IL-1R2) nor IL-1R antagonist mRNA was detected in any of the cell lines, suggesting that IL-1beta stimulated proliferation via IL-1R1. The IL-1beta -stimulated proliferation was inhibited by the MAPK kinase (MEK) inhibitor PD98059 but not by the p38 mitogen-activated protein kinase (MAPK) inhibitor SB203580 or the cyclooxygenase-2 specific inhibitor NS-398, suggesting that IL-1beta stimulated proliferation via MEK, without affecting prostaglandin E(2) synthesis. IL-1beta stimulated cellular proliferation but inhibited the synthesis of osteocalcin containing gamma-carboxylated glutamic acid (Gla-OSCAL). Both the increased proliferation and decreased Gla-OSCAL synthesis were suppressed by vitamin K(2) (VK(2)), which is a cofactor for gamma-carboxylase. Furthermore, the inhibitory effect of VK(2) on IL-1beta -stimulated proliferation was suppressed by warfarin. However, rifampicin the nuclear receptor steroid and xenobiotic receptor (SXR) ligand had no effect of IL-beta, suggesting that IL-1beta is involved in VK(2) dependent gamma-calboxylation but not SXR-activation. These results suggest that IL-1beta stimulated cellular proliferation via MEK and inhibited Gla-OSCAL synthesis, which were both inhibited by VK(2) via gamma-carboxylation.

Topics: Adult; Anticoagulants; Bone Neoplasms; Cell Line; Cell Proliferation; Cyclooxygenase 2; Cyclooxygenase Inhibitors; Dinoprostone; Enzyme Inhibitors; Flavonoids; Glutamic Acid; Humans; Imidazoles; Interleukin-1; Interleukin-1beta; Male; Mitogen-Activated Protein Kinase Kinases; Nitrobenzenes; Osteoblasts; Osteocalcin; Osteosarcoma; p38 Mitogen-Activated Protein Kinases; Pregnane X Receptor; Protein Kinase Inhibitors; Pyridines; Receptors, Steroid; Reverse Transcriptase Polymerase Chain Reaction; Rifampin; RNA, Messenger; Sulfonamides; Vitamin K; Vitamins; Warfarin; Young Adult

A white child with a long history of illness from the age of six was thought at first to have Hodgkin's disease. There followed an acute illness with lesions involving glands, lungs, bone and skin. Mycobacterium avium-intracellulare group (Battey) was isolated from various lesions at the age of thirteen. After six years of continuous treatment the patient, now eighteen, is living a normal life.

Topics: Adolescent; Bone Diseases; Bone Neoplasms; Child; Diagnosis, Differential; Ethambutol; Hodgkin Disease; Humans; Isoniazid; Kanamycin; Male; Mycobacterium; Mycobacterium avium; Mycobacterium Infections; Radiography; Rifampin; Time Factors