jueves, 27 de noviembre de 2014

Anti-cancer IAP Inhibition Increases Bone Metastasis via Unexpected Osteoclast Activation

De:

Yang C, Davis JL, Zeng R, Vora P, Su X, Collins LI, Vangveravong S, Mach RH, Piwnica-Worms D, Weilbaecher KN, Faccio R, Novack DV. Anticancer IAP inhibition increases bone metastasis via unexpected osteoclast activation. Cancer Discovery. February 2013.

This study was supported by the National Institutes of Health (NIH), grant number AR052705, with additional support from AR52921 and AR53628, CA100730, and the Barnes-Jewish Foundation. Histological and microCT analysis was supported in part by the Washington University Center for Musculoskeletal Research NIH/National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), grant number AR057235. The Molecular Imaging Center was supported by NIH grant P50 CA94056. Genentech, Inc. provided BV6.

Cancer Discov. Author manuscript; available in PMC Feb 1, 2014.

Published in final edited form as:

Cancer Discov. Feb 2013; 3(2): 212–223.

Published online Dec 26, 2012. doi: 10.1158/2159-8290.CD-12-0271

PMCID: PMC3570610

NIHMSID: NIHMS430908

Usted puede leer un resumen del artículo en:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3570610/

http://news.wustl.edu/news/Pages/24916.aspx

http://cancerdiscovery.aacrjournals.org/content/3/2/212.long

Abstract

IAP (inhibitor of apoptosis) proteins play a central role in many types of cancer, and IAP antagonists are in development as anti-cancer agents. IAP antagonists cause apoptosis in many cells, but they also activate alternative NF-κB signaling through NIK, which regulates osteoclasts. In bone metastasis, a positive feedback loop between tumors and osteoclasts promotes tumor growth and osteolysis. We therefore tested the effect of IAP antagonists on the bone microenvironment for metastasis. In both drug-sensitive and drug-resistant tumors, growth in bone was favored compared to other sites during IAP antagonist treatment. These drugs also caused osteoporosis and increased osteoclastogenesis, mediated by NIK, and enhanced tumor-associated osteolysis. Co-treatment with zoledronic acid, a potent osteoclast inhibitor, reduced IAP antagonist-enhanced tumor growth in bone and osteolysis. Thus, IAP-based cancer treatment may be compromised by osteoporosis and enhanced skeletal metastasis which may be prevented by anti-resorptive agents.

Keywords: bone metastasis, IAP antagonist, osteoclast, NF-κB, NIK

In vivo tibial compression decreases osteolysis and tumor formation in a human metastatic breast cancer model / Exercise could reduce bone tumor growth

http://www.ncbi.nlm.nih.gov/pubmed/?term=In+vivo+tibial+compression+decreases+osteolysis+and+tumor
http://www.news.cornell.edu/stories/2013/05/exercise-could-reduce-bone-tumor-growth
http://medicalxpress.com/news/2013-05-bone-tumor-growth.html

De:

Lynch, M. E., Brooks, D., Mohanan, S., Lee, M. J., Polamraju, P., Dent, K., Bonassar, L. J., van der Meulen, M. C. H. and Fischbach, C. (2013), In vivo tibial compression decreases osteolysis and tumor formation in a human metastatic breast cancer model. J Bone Miner Res, 28: 2357–2367. doi: 10.1002/jbmr.1966

Author Information

1
Biomedical Engineering, Cornell University, Ithaca, NY, USA
2
Biomedical Sciences, School of Veterinary Medicine, Cornell University, Ithaca, NY, USA
3
Mechanical and Aerospace Engineering, Cornell University, Ithaca, NY, USA
4
Research Division, Hospital for Special Surgery, New York, NY, USA
5
Kavli Institute at Cornell for Nanoscale Science, Cornell University, Ithaca, NY, USA

In vivo tibial compression decreases osteolysis and tumor formation in a human metastatic breast cancer model.

Lynch ME1, Brooks D, Mohanan S, Lee MJ, Polamraju P, Dent K, Bonassar LJ, van der Meulen MC, Fischbach C.

Author information

Abstract

Bone metastasis, the leading cause of breast cancer-related deaths, is characterized by bone degradation due to increased osteoclastic activity. In contrast, mechanical stimulation in healthy individuals upregulates osteoblastic activity, leading to new bone formation. However, the effect of mechanical loading on the development and progression of metastatic breast cancer in bone remains unclear. Here, we developed a new in vivo modelto investigate the role of skeletal mechanical stimuli on the development and osteolytic capability of secondary breast tumors. Specifically, we applied compressive loading to the tibia following intratibial injection of metastatic breast cancer cells (MDA-MB231) into the proximal compartment of female immunocompromised (SCID) mice. In the absence of loading, tibiae developed histologically-detectable tumors with associated osteolysis and excessive degradation of the proximal bone tissue. In contrast, mechanical loading dramatically reduced osteolysis and tumor formation and increased tibial cancellous mass due to trabecular thickening. These loading effects were similar to the baseline response we observed in non-injected SCID mice. In vitro mechanical loading of MDA-MB231 in a pathologically relevant 3D culture model suggested that the observed effects were not due to loading-induced tumor cell death, but rather mediated via decreased expression of genes interfering with bone homeostasis. Collectively, our results suggest that mechanical loading inhibits the growth and osteolytic capability of secondary breast tumors after their homing to the bone, which may inform future treatment of breast cancer patients with advanced disease.

© 2013 American Society for Bone and Mineral Research.

KEYWORDS:

BREAST CANCER; MECHANICAL LOADING; METASTASIS; OSTEOLYSIS

Compresión tbial en vivo disminuye la osteolisis y formación de tumores en un modelo de cáncer de mama metastásico humano / El ejercicio podría reducir el crecimiento del tumor óseo

د-عبد المنعم جمعه Pfn...curetage and bone graft..better to deal with both problems at same sitting

18 horas · Me gusta
Dalshukh Parmar no only long pf nail

17 horas · Me gusta
Amitava Narayan Mukherjee Pfn get ready for encercalge if situation demands

16 horas · Me gusta
Mohamed Farouk Zaky 1st stage then fix

14 horas · Me gusta
Drsd Khetani If biopsy report permits currettage & BG could also attempted for the cystic leison along with pfn etc.

13 horas · Me gusta
Melvin J George PFN....

10 horas · Me gusta
Srinivas Daravathu Take an Mri

10 horas · Me gusta
Srinivas Daravathu Anyone comment on the lesion?

10 horas · Me gusta
Anuj Agrawal It's a benign, inactive lesion, with thick sclerotic borders. I would not curette it, but only take a biopsy during the course of nailing.