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Inhibition of Notch pathway prevents osteosarcoma growth by cell cycle regulation
British Journal of Cancer, 05/22/09
Tanaka M et al. - In a study to determine how the Notch pathway is involved in the pathogenesis of osteosarcoma, it was concluded that inhibition of Notch pathway suppresses osteosarcoma growth by regulation of cell cycle regulator expression and that the inactivation of the Notch pathway may be a useful approach to the treatment of patients with osteosarcoma.
Methods- Expression of the Notch pathway molecules was investigated in osteosarcoma biopsy specimens and the effect of Notch pathway inhibition was examined.
- Real-time PCR revealed overexpression of Notch2, Jagged1, HEY1, and HEY2.
- Notch1 and DLL1 were downregulated in biopsy specimens.
- Notch pathway inhibition using γ-secretase inhibitor and CBF1 siRNA slowed the growth of osteosarcomas in vitro.
- γ-secretase inhibitor-treated xenograft models exhibited significantly slower osteosarcoma growth.
- Cell cycle analysis revealed that γ-secretase inhibitor promoted G1 arrest.
- Real-time PCR and western blot revealed that γ-secretase inhibitor reduced the expression of accelerators of the cell cycle, including cyclin D1, cyclin E1, E2, and SKP2.
- p21cip1 protein, a cell cycle suppressor, was upregulated by γ-secretase inhibitor treatment.
Today in Basic Science/Genetics...keeping you current
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Serum calcium levels are elevated among women with untreated postmenopausal breast cancer
Cancer Causes and Control, 11/03/09
Prognostic and predictive value of HER2 extracellular domain in metastatic breast cancer treated with lapatinib and paclitaxel in a randomized phase III study
Journal of Clinical Oncology, 10/29/09
Contralateral breast cancer risk in BRCA1 and BRCA2 mutation carriers
Journal of Clinical Oncology, 10/29/09
Today in Bone/Cartilage...keeping you current
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Multidisciplinary treatment including sorafenib stabilized the bone metastases of renal cell carcinoma in an immunosuppressed renal transplant recipient
International Journal of Clinical Oncology, 10/30/09
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Toxicity of Bisphosphonates
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Today in Soft Tissue/Sarcoma...keeping you current
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Adjuvant Chemotherapy in Localized Soft Tissue Sarcomas: Still Not Proven
The Oncologist, 10/28/09
Randomized Trial and Pharmacokinetic Study of Pegfilgrastim versus Filgrastim after Dose-Intensive Chemotherapy in Young Adults and Children with Sarcomas
Clinical Cancer Research, 11/20/09
Incidence and Correlates of Radiation Dermatitis in Children and Adolescents Receiving Radiation Therapy for the Treatment of Paediatric Sarcomas
Clinical Oncology, 11/12/09
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