Displaying publications 41 - 43 of 43 in total

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  1. Jeevaratnam K, Salvage SC, Li M, Huang CL
    Ann N Y Acad Sci, 2018 Dec;1433(1):18-28.
    PMID: 29846007 DOI: 10.1111/nyas.13861
    Alterations in cellular levels of the second messenger 3',5'-cyclic adenosine monophosphate ([cAMP]i ) regulate a wide range of physiologically important cellular signaling processes in numerous cell types. Osteoclasts are terminally differentiated, multinucleated cells specialized for bone resorption. Their systemic regulator, calcitonin, triggers morphometrically and pharmacologically distinct retraction (R) and quiescence (Q) effects on cell-spread area and protrusion-retraction motility, respectively, paralleling its inhibition of bone resorption. Q effects were reproduced by cholera toxin-mediated Gs -protein activation known to increase [cAMP]i , unaccompanied by the [Ca2+ ]i changes contrastingly associated with R effects. We explore a hypothesis implicating cAMP signaling involving guanine nucleotide-exchange activation of the small GTPase Ras-proximate-1 (Rap1) by exchange proteins directly activated by cAMP (Epac). Rap1 activates integrin clustering, cell adhesion to bone matrix, associated cytoskeletal modifications and signaling processes, and transmembrane transduction functions. Epac activation enhanced, whereas Epac inhibition or shRNA-mediated knockdown compromised, the appearance of markers for osteoclast differentiation and motility following stimulation by receptor activator of nuclear factor kappa-Β ligand (RANKL). Deficiencies in talin and Rap1 compromised in vivo bone resorption, producing osteopetrotic phenotypes in genetically modified murine models. Translational implications of an Epac-Rap1 signaling hypothesis in relationship to N-bisphosphonate actions on prenylation and membrane localization of small GTPases are discussed.
    Matched MeSH terms: Bone Density Conservation Agents/pharmacology
  2. Shuid AN, Mehat Z, Mohamed N, Muhammad N, Soelaiman IN
    J Bone Miner Metab, 2010 Mar;28(2):149-56.
    PMID: 19779668 DOI: 10.1007/s00774-009-0122-2
    Recently, vitamin E has been found to promote the bone structure of nicotine-treated rats well above their baseline values, thus suggesting that vitamin E may have some anabolic action. A bone anabolic agent acts by improving the bone structure leading to stronger bone. To assess the possible anabolic action vitamin E on bone, we supplemented alpha-tocopherol (ATF) or gamma-tocotrienol (GTT) at 60 mg/kg or vehicle [normal control (NC) group] for 4 months to normal male rats and measured their bone structure and biomechanical properties. Histomorphometric analysis revealed that vitamin E-supplemented rats have better trabecular volume, thickness, number, and separation than rats receiving vehicle only. For the first time we reported that GTT improves all the parameters of bone biomechanical strength, while ATF only improved some of the parameters compared to the NC group. Vitamin E supplementation, especially with the gamma isomer, improves bone structure, which contributed to stronger bone. Therefore, vitamin E has the potential to be used as an anabolic agent to treat osteoporosis or as bone supplements for young adults to prevent osteoporosis in later years.
    Matched MeSH terms: Bone Density Conservation Agents/administration & dosage
  3. Hassan BA, Yusoff ZB, Hassali MA, Othman SB, Weiderpass E
    Asian Pac J Cancer Prev, 2012;13(9):4373-8.
    PMID: 23167346
    INTRODUCTION: Hypercalcemia is mainly caused by bone resorption due to either secretion of cytokines including parathyroid hormone-related protein (PTHrP) or bone metastases. However, hypercalcemia may occur in patients with or without bone metastases. The present study aimed to describe the effect of chemotherapy treatment, regimens and doses on calcium levels among breast and lung cancer patients with hypercalcemia.

    METHODS: We carried a review of medical records of breast and lung cancer patients hospitalized in years 2003 and 2009 at Penang General Hospital, a public tertiary care center in Penang Island, north of Malaysia. Patients with hypercalcemia (defined as a calcium level above 10.5 mg/dl) at the time of cancer diagnosis or during cancer treatment had their medical history abstracted, including presence of metastasis, chemotherapy types and doses, calcium levels throughout cancer treatment, and other co-morbidity. The mean calcium levels at first hospitalization before chemotherapy were compared with calcium levels at the end of or at the latest chemotherapy treatment. Statistical analysis was conducted using the Chi-square test for categorical data, logistic regression test for categorical variables, and Spearman correlation test, linear regression and the paired sample t tests for continuous data.

    RESULTS: Of a total 1,023 of breast cancer and 814 lung cancer patients identified, 292 had hypercalcemia at first hospitalization or during cancer treatment (174 breast and 118 lung cancer patients). About a quarter of these patients had advanced stage cancers: 26.4% had mild hypercalcemia (10.5-11.9 mg/dl), 55.5% had moderate (12-12.9 mg/dl), and 18.2% severe hypercalcemia (13-13.9; 14-16 mg/dl). Chemotherapy lowered calcium levels significantly both in breast and lung cancer patients with hypercalcemia; in particular with chemotherapy type 5-flurouracil+epirubicin+cyclophosphamide (FEC) for breast cancer, and gemcitabine+cisplatin in lung cancer.

    CONCLUSION: Chemotherapy decreases calcium levels in breast and lung cancer cases with hypercalcemia at cancer diagnosis, probably by reducing PTHrP levels.

    Matched MeSH terms: Bone Density Conservation Agents/therapeutic use
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