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Introduction: Osteoporosis is the most prevalent bone disease in humans, affecting people of all ages but more common in postmenopausal women. Risedronate (RIS) and strontium ranelate (SR) are two clinically accessible anti-osteoporotic medicines. Objectives: To assess and compare the anti-osteoporotic effects of RIS and SR on the histologic, histomorphometric, and ultrastructural features of compact bones in a rat model of glucocorticoid-induced osteoporosis. Materials and Methods: 42 mature healthy male albino rats were randomly allocated into 6 main groups (7 rats /group) and received daily oral treatments for 12 weeks as following: negative control, RIS +ve control (2.5 mg/kg/day), SR +ve control (625 mg/kg/day), prednisolone (pred)-treated (1.5 mg/kg/day), pred + RIS (treated concurrently with prednisolone and RIS), and pred + SR (treated concurrently with prednisolone and SR). At the end of the experiment, all animals were anesthetized, sacrificed, and the femurs and tibias were excised for x-ray, histological, histomorphometric, and electron microscopic studies. Results: Oral prednisolone provoked significant osteoporotic changes as evidenced by generalized osteopenia and bone bending detected in the X-ray. Histological examination demonstrated decreased cortical bone thickness, multiple irregular perforations, reduced lamellar bone formation, and an increase in the osteoid tissue. Ultrastructural changes were observed in the form of distorted osteoblasts and osteocytes together with lysis of collagen fibrils in the bone matrix. Oral administration of RIS and SR was associated with moderate and marked improvement of prednisolone induced perturbations of the bone architecture respectively. Conclusion: Our data suggest that SR outperforms RIS in alleviating glucocorticoid-induced osteoporotic changes in cortical bone tissues. [ABSTRACT FROM AUTHOR]

Despite advancement in breast cancer treatment, 30% of patients with early breast cancers experience relapse with distant metastasis. It is a challenge to identify patients at risk for relapse; therefore, the identification of markers and therapeutic targets for metastatic breast cancers is imperative. Here, we identified DP103 as a biomarker and metastasis-driving oncogene in human breast cancers and determined that DP103 elevates matrix metallopeptidase 9 (MMP9) levels, which are associated with metastasis and invasion through activation of NF-κB. In turn, NF- κB signaling positively activated DP103 expression. Furthermore, DP103 enhanced TGF-β-activated kinase-1 (TAK1) phosphorylation of NF-κB-activating IκB kinase 2 (IKK2), leading to increased NF-κB activity. Reduction of DP103 expression in invasive breast cancer cells reduced phosphorylation of IKK2, abrogated NF-κB- mediated MMP9 expression, and impeded metastasis in a murine xenograft model. In breast cancer patient tissues, elevated levels of DP103 correlated with enhanced MMP9, reduced overall survival, and reduced survival after relapse. Together, these data indicate that a positive DP103/NF-κB feedback loop promotes constitutive NF-κB activation in invasive breast cancers and activation of this pathway is linked to cancer progression and the acquisition of chemotherapyresistance. Furthermore, our results suggest that DP103 has potential as a therapeutic target for breast cancer treatment., Introduction Breast carcinoma is one of the most common malignancies in women around the world. Mortality from breast cancer is almost entirely the result of invasion and metastasis of neoplastic [...]

Despite advancement in breast cancer treatment, 30% of patients with early breast cancers experience relapse with distant metastasis. It is a challenge to identify patients at risk for relapse; therefore, the identification of markers and therapeutic targets for metastatic breast cancers is imperative. Here, we identified DP103 as a biomarker and metastasis-driving oncogene in human breast cancers and determined that DP103 elevates matrix metallopeptidase 9 (MMP9) levels, which are associated with metastasis and invasion through activation of NF-κB. In turn, NF-κB signaling positively activated DP103 expression. Furthermore, DP103 enhanced TGF-β--activated kinase-1 (TAK1) phosphorylation of NF-κB--activating IκB kinase 2 (IKK2), leading to increased NF-κB activity. Reduction of DP103 expression in invasive breast cancer cells reduced phosphorylation of IKK2, abrogated NF-κB--mediated MMP9 expression, and impeded metastasis in a murine xenograft model. In breast cancer patient tissues, elevated levels of DP103 correlated with enhanced MMP9, reduced overall survival, and reduced survival after relapse. Together, these data indicate that a positive DP103/NF-κB feedback loop promotes constitutive NF-κB activation in invasive breast cancers and activation of this pathway is linked to cancer progression and the acquisition of chemotherapy resistance. Furthermore, our results suggest that DP103 has potential as a therapeutic target for breast cancer treatment. [ABSTRACT FROM AUTHOR]