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)

N-BP, rapamycin and its derivatives have been originally developed respectively as anti-resorptive and anti-fungal agents. In fact, in vitro and in vivo experiments demonstrated that these compounds are multi-functional molecules exerting their effects on tumour cell growth and bone remodelling. The major challenge in treating cancer relates to mutations in key genes such as p53, Rb or proteins affecting caspase signalling carried by many tumour cells. Whether nitrogen containing bisphosphonates (N-BP) are potent bone inhibitors, they also inhibit tumour cell proliferation and increase atypical apoptosis of bone tumour cells regardless of the p53 and Rb status. N-BP may be then considered as effective therapeutic agents in clinical trials of bone tumours. Rapamycin and its derivatives inhibit mTOR dependent mRNA translation both in osteoclasts and tumour cells. Cellular physiological mechanisms regulated by mTOR integrate many environmental parameters including growth factors, hormones, cytokines, amino acids, energy availability and cellular stresses that are coupled with cell cycle progression and cell growth. Rapamycin and its derivatives as well as N-BP must be considered as bi-(multi) functional molecules affecting simultaneously bone and tumour metabolisms. The present survey describes these two molecular families and discusses their therapeutic interests for primary bone tumours and bone metastases.
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PMID:mTOR inhibitors (rapamycin and its derivatives) and nitrogen containing bisphosphonates: bi-functional compounds for the treatment of bone tumours. 1758 50

In advanced breast cancer, bone metastases occur in 70 % of patients. Managing the devastating pain associated with the disease is difficult. Rapamycin is an immunomodulatory drug that targets the mammalian target of rapamycin pathway. Rapamycin has been shown to decrease osteolysis associated with metastatic breast cancer in pre-clinical models and to reduce pain in inflammatory and neuropathic models. The aim of this study was to evaluate the effectiveness of rapamycin in reducing pain associated with experimental osteolytic metastases. Bone cancer was induced by intra-tibial injections of murine mammary carcinoma cells (4T1) in immunocompetent BALB/c mice and treated intraperitoneally for up to 5 weeks with vehicle, rapamycin or pamidronate (a bisphosphonate currently used to reduce bone loss in bone cancer patients). The control group received intra-tibial injection with saline (sham) and was treated with vehicle intraperitoneally. Cancer-induced osteolysis was observed histologically and radiographically 2-3 weeks following cancer inoculation and gradually increased with time. Measures of evoked nociceptive behaviors including sensitivity to mechanical, thermal, and cold stimuli and spontaneous nociceptive behaviors (limping, guarding) were evaluated. Significant hypersensitivity to sensory stimuli developed in cancer-bearing mice compared to sham 3 weeks following inoculation. Rapamycin decreased or delayed the development of cancer-induced mechanical, heat, and cold hypersensitivity, while pamidronate reduced heat and cold hypersensitivity. Both rapamycin and pamidronate had a partial protective effect on the spontaneous nociceptive behaviors, limping and guarding. Our data suggest that rapamycin may have efficacy in the management of pain associated with metastatic breast cancer.
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PMID:Osteolysis and pain due to experimental bone metastases are improved by treatment with rapamycin. 2432 32