ABSTRACT
Gliomas are the most prevalent type of primary brain tumors in adults, accounting for more than 40% of neoplasms in the central nervous system. The spen paralogue and orthologue C-terminal domain containing 1 (SPOCD1) has been recently identified and found to discriminate progressive from non-progressive bladder cancers. In this study, we detected high-level of SPOCD1 expression in glioma and its high expression significantly associated with advanced tumor grade and poor prognosis. In vitro assays showed that knockdown of SPOCD1 significantly inhibited cell proliferation and colony formation capacities in U373 and U87 cells. In a xenograft model of glioma, SPOCD1 was also found to inhibit tumor growth. In addition, knockdown of SPOCD1 was shown to inhibit cell migration and invasion in glioma U373 and U87 cells. SPOCD1 positively regulated the expression of Pentraxin 3 (PTX3), whereas overexpression of PTX3 attenuated SPOCD1 knockdown-mediated inhibition of cell proliferation, migration and invasion in glioma cells. Our observations suggest that SPOCD1 promotes the proliferation and metastasis of glioma cells through regulating PTX3. Our data might provide novel evidence for the diagnosis and treatment of glioma in clinic.
ABSTRACT
OBJECTIVE: To investigate musculoskeletal disorders and risk factors of low back pain in multiple sclerosis (MS) patients. METHODS: In this study, patients in our hospital with confirmed MS with an expanded disabilitystatus scale (EDSS) score between 4 to 7 were selected. Data of MS history, pain, musculoskeletal disorders, muscle strength and spasticity in lower limbs were collected. RESULTS: Among 190 patients, there were 61 males and 129 females, with an average age of(54.9±9.2) years old. The mean disease duration was(19.3±9.9) years, and the median EDSS score was 6. Forty-two patients were relapsing-remitting type, 45 patients were primary progressive type, and 93 patients were secondary progressive type. The most common musculoskeletal disorders were described as follows:knee osteoarthritis (15 cases), claw toe (13 cases) and genu recurvatum (12 cases). Seventy-nine patients with prevalence low back pain was higher than in patients with a progressive type(secondary: OR=2.958, P=0.007 9, primary(OR=2.629, P=0.039 8) and in patients who had a visual dysfunction at EDSS score(OR=1.411, P=0.012 4). The prevalence was reduced in male patients(OR=0.306, P=0.001 4). CONCLUSIONS: The progressive type of MS and visual dysfunction increased the risk of low back pain in these patients.
Subject(s)
Low Back Pain/etiology , Multiple Sclerosis, Chronic Progressive/complications , Multiple Sclerosis, Relapsing-Remitting/complications , Female , Humans , Low Back Pain/epidemiology , Male , Middle Aged , Risk FactorsABSTRACT
Chemoresistance is a major obstacle to successful chemotherapy for glioma. Formononetin is a novel herbal isoflavonoid isolated from Astragalus membranaceus and possesses antitumorigenic properties. In the present study, we investigated the anti-proliferative effects of formononetin on human glioma cells, and further elucidated the molecular mechanism underlying the anti-tumor property. We found that formononetin enhanced doxorubicin cytotoxicity in glioma cells. Combined treatment with formononetin reversed the doxorubicin-induced epithelial-mesenchymal transition (EMT) in tumor cells. Moreover, we found that formononetin treatment significantly decreased the expression of HDAC5. Overexpression of HDAC5 diminished the suppressive effects of formononetin on glioma cell viability. Furthermore, knockdown of HDAC5 by siRNA inhibited the doxorubicin-induced EMT in glioma cells. Taken together, these results demonstrated that formononetin-combined therapy may enhance the therapeutic efficacy of doxorubicin in glioma cells by preventing EMT through inhibition of HDAC5.
Subject(s)
Antibiotics, Antineoplastic/pharmacology , Antineoplastic Combined Chemotherapy Protocols/pharmacology , Brain Neoplasms/drug therapy , Doxorubicin/pharmacology , Epithelial-Mesenchymal Transition/drug effects , Glioma/drug therapy , Histone Deacetylase Inhibitors/pharmacology , Histone Deacetylases/metabolism , Isoflavones/pharmacology , Brain Neoplasms/enzymology , Brain Neoplasms/genetics , Brain Neoplasms/pathology , Cell Line, Tumor , Dose-Response Relationship, Drug , Gene Expression Regulation, Enzymologic , Gene Expression Regulation, Neoplastic , Glioma/enzymology , Glioma/genetics , Glioma/pathology , Histone Deacetylases/genetics , Humans , RNA Interference , Signal Transduction/drug effects , TransfectionABSTRACT
Histone deacetylases (HDACs) constitute a family of enzymes that play important roles in the epigenetic regulation of gene expression and contribute to the growth, differentiation and apoptosis of cancer cells. However, the biological function of HDAC5 in glioma cells has not been fully understood. In the present study, we found that the mRNA and protein levels of HDAC5 are increased in human glioma tissues and cell lines. In addition, overexpression of HDAC5 promoted proliferation of glioma cells, as measured by the MTT assay. By contrast, HDAC5 gene silencing using small interfering RNA (siRNA) inhibited cell proliferation. Furthermore, we demonstrated that HDAC5 enhances Notch 1 expression at both the mRNA and the protein level in glioma cell lines. Taken together, these results demonstrated, for the first time to the best of our knowledge, that HDAC5 promotes glioma cell proliferation, and suggest that this effect involves the upregulation of Notch 1. Therefore, our study may provide a novel therapeutic target for treatment of gliomas.
