human
The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.
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    INPUT: BACKGROUND Induction of osteolytic bone lesions in multiple myeloma is caused by an uncoupling of osteoclastic bone resorption and osteoblastic bone formation . Current management of myeloma bone disease is limited to the use of antiresorptive agents such as bisphosphonates . METHODOLOGY/PRINCIPAL FINDINGS We tested the effects of daily administered parathyroid hormone ( PTH ) on bone disease and myeloma growth , and we investigated molecular mechanisms by analyzing gene expression profiles of unique myeloma cell lines and primary myeloma cells engrafted in SCID-rab and SCID-hu mouse models . PTH resulted in increased bone mineral density of myelomatous bones and reduced tumor burden , which reflected the dependence of primary myeloma cells on the bone marrow microenvironment . Treatment with PTH also increased bone mineral density of uninvolved murine bones in myelomatous hosts and bone mineral density of implanted human bones in nonmyelomatous hosts . In myelomatous bone , PTH markedly increased the number of osteoblasts and bone-formation parameters , and the number of osteoclasts was unaffected or moderately reduced . Pretreatment with PTH before injecting myeloma cells increased bone mineral density of the implanted bone and delayed tumor progression . Human global gene expression profiling of myelomatous bones from SCID-hu mice treated with PTH or saline revealed activation of multiple distinct pathways involved in bone formation and coupling ; involvement of Wnt signaling was prominent . Treatment with PTH also downregulated markers typically expressed by osteoclasts and myeloma cells , and altered expression of genes that control oxidative stress and inflammation . PTH receptors were not expressed by myeloma cells , and PTH had no effect on myeloma cell growth in vitro . CONCLUSIONS/SIGNIFICANCE We conclude that PTH-induced bone formation in myelomatous bones is mediated by activation of multiple signaling pathways involved in osteoblastogenesis and attenuated bone resorption and myeloma growth ; mechanisms involve increased osteoblast production of anti-myeloma factors and minimized myeloma induction of inflammatory conditions .
    OUTPUT:

agent
tumor promoting inflammation
The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.
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    INPUT: BACKGROUND Induction of osteolytic bone lesions in multiple myeloma is caused by an uncoupling of osteoclastic bone resorption and osteoblastic bone formation . Current management of myeloma bone disease is limited to the use of antiresorptive agents such as bisphosphonates . METHODOLOGY/PRINCIPAL FINDINGS We tested the effects of daily administered parathyroid hormone ( PTH ) on bone disease and myeloma growth , and we investigated molecular mechanisms by analyzing gene expression profiles of unique myeloma cell lines and primary myeloma cells engrafted in SCID-rab and SCID-hu mouse models . PTH resulted in increased bone mineral density of myelomatous bones and reduced tumor burden , which reflected the dependence of primary myeloma cells on the bone marrow microenvironment . Treatment with PTH also increased bone mineral density of uninvolved murine bones in myelomatous hosts and bone mineral density of implanted human bones in nonmyelomatous hosts . In myelomatous bone , PTH markedly increased the number of osteoblasts and bone-formation parameters , and the number of osteoclasts was unaffected or moderately reduced . Pretreatment with PTH before injecting myeloma cells increased bone mineral density of the implanted bone and delayed tumor progression . Human global gene expression profiling of myelomatous bones from SCID-hu mice treated with PTH or saline revealed activation of multiple distinct pathways involved in bone formation and coupling ; involvement of Wnt signaling was prominent . Treatment with PTH also downregulated markers typically expressed by osteoclasts and myeloma cells , and altered expression of genes that control oxidative stress and inflammation . PTH receptors were not expressed by myeloma cells , and PTH had no effect on myeloma cell growth in vitro . CONCLUSIONS/SIGNIFICANCE We conclude that PTH-induced bone formation in myelomatous bones is mediated by activation of multiple signaling pathways involved in osteoblastogenesis and attenuated bone resorption and myeloma growth ; mechanisms involve increased osteoblast production of anti-myeloma factors and minimized myeloma induction of inflammatory conditions .
    OUTPUT:
