HER2 Support Group Forums - View Single Post - BPH-715 (revised Zoledronate) A New Weapon Against Tumor Cells

Rich66 · 09-29-2009, 01:06 PM

1: Anticancer Res. 2009 Jun;29(6):1879-88. Links: Alendronate inhibits growth of high-grade chondrosarcoma cells.

Susa M, Morii T, Yabe H, Horiuchi K, Toyama Y, Weissbach L, Hornicek FJ, Morioka H.
Department of Orthopaedic Surgery, Keio University School of Medicine, Tokyo, Japan. msusa@partners.org
BACKGROUND: Conventional chemotherapy is ineffective for high-grade chondrosarcomas, highlighting the need for improved chemotherapies. Various clinical trials have been initiated using antiapoptotic agents and perifosine, and are truly in the experimental phases. Chondrosarcoma is still therefore considered a surgical disease despite its aggressive features of recurring locally and spreading to the lungs. Bisphosphonates inhibit growth of various cell types, including cancer cells and perhaps chondrosarcoma. MATERIALS AND METHODS: The effect of different concentrations of alendronate on cell proliferation, migration, apoptosis and cytoskeleton reorganization as well as on the regulation of intracellular protein expression were analyzed for the high-grade chondrosarcoma cell line CS-1. Mevalonate pathway intermediates were used in some experiments to assess mechanistic aspects. RESULTS: Alendronate decreased cell viability of CS-1 by inhibiting cell proliferation and cell migration. Alendronate-induced loss of cell viability led to a sequence of events including apoptosis and cytoskeletal rearrangements. Moreover, changes in the expression levels of various proteins involved in cell proliferation, migration, cell cycle, apoptosis and cytoskeleton reorganization were demonstrated. CONCLUSION: Alendronate exerts antiproliferative effects by perturbing various signaling pathways in CS-1 cells. These findings may lead to new treatment options for high-grade chondrosarcoma.
PMID: 19528443 [PubMed - indexed for MEDLINE]

Support Care Cancer. 2010 Feb 12. [Epub ahead of print]
Bone pain reduction in patients with metastatic breast cancer treated with ibandronate-results from a post-marketing surveillance study.

Diel IJ, Kurth AH, Sittig HB, Meden H, Maasberg M, Sandermann A, Bergner R.
Institute for Gynaecological Oncology, CGG-Clinic, P7, 16-18, 68161, Mannheim, Germany, diel@cgg-mannheim.de.
BACKGROUND: Pain relief is an important treatment goal for breast cancer patients with metastatic bone disease and treatment should be associated with a low rate of side effects. This interim analysis of a prospective non-interventional study documents the efficacy and safety of the amino-bisphosphonate ibandronate in the treatment of metastatic bone disease under real-life conditions. PATIENTS AND METHODS: For up to 24 weeks 913 breast cancer patients received IV infusions of 6 mg ibandronate every 3-4 weeks or 50 mg of oral ibandronate once daily. Efficacy variables included pain severity, analgesic use, and skeletal-related events; the major safety parameter was renal function, assessed by serum creatinine levels. Subgroup analyses were performed according to pretreatment with bisphosphonates (none, ibandronate, or other bisphosphonates). RESULTS: At baseline, patients with ibandronate pretreatment tended to have lower mean pain scores and lower serum creatinine levels than those pre-treated with other bisphosphonates. Over the observation period, analgesic use did not increase. Among the 712 patients reporting pain at baseline, 70% achieved an improvement in pain severity during treatment with ibandronate, and there was no evidence to suggest relevant differences in mean pain reductions with IV or oral administration of ibandronate or according to prior bisphosphonate treatment. Skeletal-related events were rare (7%). Changes in serum creatinine levels during ibandronate treatment were small and both formulations of ibandronate were rated as well tolerated by physicians and patients. CONCLUSIONS: Data from this non-interventional study confirm the analgesic efficacy and safety profile of IV and oral ibandronate under real-life conditions.

PMID: 20151162 [PubMed - as supplied by publisher]

09-29-2009, 01:06 PM	#22
Rich66 Senior Member Join Date: Feb 2008 Location: South East Wisconsin Posts: 3,431	Re: BPH-715 (revised Zoledronate) A New Weapon Against Tumor Cells 1: Anticancer Res. 2009 Jun;29(6):1879-88. Links Alendronate inhibits growth of high-grade chondrosarcoma cells. Susa M, Morii T, Yabe H, Horiuchi K, Toyama Y, Weissbach L, Hornicek FJ, Morioka H. Department of Orthopaedic Surgery, Keio University School of Medicine, Tokyo, Japan. msusa@partners.org BACKGROUND: Conventional chemotherapy is ineffective for high-grade chondrosarcomas, highlighting the need for improved chemotherapies. Various clinical trials have been initiated using antiapoptotic agents and perifosine, and are truly in the experimental phases. Chondrosarcoma is still therefore considered a surgical disease despite its aggressive features of recurring locally and spreading to the lungs. Bisphosphonates inhibit growth of various cell types, including cancer cells and perhaps chondrosarcoma. MATERIALS AND METHODS: The effect of different concentrations of alendronate on cell proliferation, migration, apoptosis and cytoskeleton reorganization as well as on the regulation of intracellular protein expression were analyzed for the high-grade chondrosarcoma cell line CS-1. Mevalonate pathway intermediates were used in some experiments to assess mechanistic aspects. RESULTS: Alendronate decreased cell viability of CS-1 by inhibiting cell proliferation and cell migration. Alendronate-induced loss of cell viability led to a sequence of events including apoptosis and cytoskeletal rearrangements. Moreover, changes in the expression levels of various proteins involved in cell proliferation, migration, cell cycle, apoptosis and cytoskeleton reorganization were demonstrated. CONCLUSION: Alendronate exerts antiproliferative effects by perturbing various signaling pathways in CS-1 cells. These findings may lead to new treatment options for high-grade chondrosarcoma. PMID: 19528443 [PubMed - indexed for MEDLINE] Support Care Cancer. 2010 Feb 12. [Epub ahead of print] Bone pain reduction in patients with metastatic breast cancer treated with ibandronate-results from a post-marketing surveillance study. Diel IJ, Kurth AH, Sittig HB, Meden H, Maasberg M, Sandermann A, Bergner R. Institute for Gynaecological Oncology, CGG-Clinic, P7, 16-18, 68161, Mannheim, Germany, diel@cgg-mannheim.de. BACKGROUND: Pain relief is an important treatment goal for breast cancer patients with metastatic bone disease and treatment should be associated with a low rate of side effects. This interim analysis of a prospective non-interventional study documents the efficacy and safety of the amino-bisphosphonate ibandronate in the treatment of metastatic bone disease under real-life conditions. PATIENTS AND METHODS: For up to 24 weeks 913 breast cancer patients received IV infusions of 6 mg ibandronate every 3-4 weeks or 50 mg of oral ibandronate once daily. Efficacy variables included pain severity, analgesic use, and skeletal-related events; the major safety parameter was renal function, assessed by serum creatinine levels. Subgroup analyses were performed according to pretreatment with bisphosphonates (none, ibandronate, or other bisphosphonates). RESULTS: At baseline, patients with ibandronate pretreatment tended to have lower mean pain scores and lower serum creatinine levels than those pre-treated with other bisphosphonates. Over the observation period, analgesic use did not increase. Among the 712 patients reporting pain at baseline, 70% achieved an improvement in pain severity during treatment with ibandronate, and there was no evidence to suggest relevant differences in mean pain reductions with IV or oral administration of ibandronate or according to prior bisphosphonate treatment. Skeletal-related events were rare (7%). Changes in serum creatinine levels during ibandronate treatment were small and both formulations of ibandronate were rated as well tolerated by physicians and patients. CONCLUSIONS: Data from this non-interventional study confirm the analgesic efficacy and safety profile of IV and oral ibandronate under real-life conditions. PMID: 20151162 [PubMed - as supplied by publisher]