ABSTRACT
PURPOSE: This study was designed to investigate the expression levels of the inhibitor of apoptosis protein Livin in nasopharyngeal cancer tissues and its prognostic significance in nasopharyngeal carcinoma after radiotherapy. MATERIAL AND METHODS: A total of 83 patients with nasopharyngeal carcinoma who received radiotherapy were enrolled in this study from January 2008 to October 2010. Livin expression in nasopharynx pathological specimens extracted from patients was detected by immunohistochemistry. A Kaplan-Meier analysis was conducted to explore the effects of clinicopathological features and Livin expression on the overall survival and progression-free survival of patients with nasopharyngeal carcinoma, and explore its prognosis relevance after radiotherapy. RESULTS: Of the 83 patients with nasopharyngeal carcinoma, the overall Livin positive expression rate was 65.1% (54 patients), and the overall response rate of radiotherapy was 81.9% (68 patients). Significant differences in radiotherapy efficacy were found between patients who did not express Livin and those who did (P<0.05). The Kaplan-Meier analysis showed that Livin expression, high clinical staging, cervical lymph node metastasis, high T-staging and high N-staging were significantly correlated with a decrease in the overall survival of patients with nasopharyngeal carcinoma (all P<0.05). A Cox multivariate survival analysis showed that Livin expression, clinical staging and N-staging were independent risk factors for the overall survival of patients with nasopharyngeal carcinoma treated with radiation (all P<0.05). Furthermore, Livin expression and clinical staging were independent risk factors for the progression-free survival of patients with nasopharyngeal carcinoma once radiotherapy was introduced (all P<0.05). CONCLUSION: Expression of Livin, an inhibitor of apoptosis proteins, may be closely linked with poor prognosis of nasopharyngeal carcinoma post-radiotherapy and hence it may be a new therapeutic target in the treatment of the disease.
Subject(s)
Adaptor Proteins, Signal Transducing/metabolism , Inhibitor of Apoptosis Proteins/metabolism , Nasopharyngeal Neoplasms/metabolism , Nasopharyngeal Neoplasms/mortality , Neoplasm Proteins/metabolism , Adult , Aged , Biomarkers, Tumor/metabolism , Carcinoma/metabolism , Carcinoma/mortality , Carcinoma/pathology , Carcinoma/radiotherapy , Female , Humans , Immunohistochemistry , Lymphatic Metastasis , Male , Middle Aged , Multivariate Analysis , Nasopharyngeal Neoplasms/pathology , Nasopharyngeal Neoplasms/radiotherapy , Prognosis , Young AdultABSTRACT
Mechanical stimulation and histone deacetylases (HDACs) have essential roles in regulating the osteogenic differentiation of bone marrow stromal cells (BMSCs) and bone formation. However, little is known regarding what regulates HDAC expression and therefore the osteogenic differentiation of BMSCs during osteogenesis. In this study, we investigated whether mechanical loading regulates HDAC expression directly and examined the role of HDACs in mechanical loading-triggered osteogenic differentiation and bone formation. We first studied the microarrays of samples from patients with osteoporosis and found that the NOTCH pathway and skeletal development gene sets were downregulated in the BMSCs of patients with osteoporosis. Then we demonstrated that mechanical stimuli can regulate osteogenesis and bone formation both in vivo and in vitro. NOTCH signaling was upregulated during cyclic mechanical stretch (CMS)-induced osteogenic differentiation, whereas HDAC1 protein expression was downregulated. The perturbation of HDAC1 expression also had a significant effect on matrix mineralization and JAG1-mediated Notch signaling, suggesting that HDAC1 acts as an endogenous attenuator of Notch signaling in the mechanotransduction of BMSCs. Chromatin immunoprecipitation (ChIP) assay results suggest that HDAC1 modulates the CMS-induced histone H3 acetylation level at the JAG1 promoter. More importantly, we found an inhibitory role of Hdac1 in regulating bone formation in response to hindlimb unloading in mice, and pretreatment with an HDAC1 inhibitor partly rescued the osteoporosis caused by mechanical unloading. Our results demonstrate, for the first time, that mechanical stimulation orchestrates genes expression involved in the osteogenic differentiation of BMSCs via the direct regulation of HDAC1, and the therapeutic inhibition of HDAC1 may be an efficient strategy for enhancing bone formation under mechanical stimulation.
Subject(s)
Histone Deacetylase 1/genetics , Mechanotransduction, Cellular , Mesenchymal Stem Cells/metabolism , Osteogenesis/genetics , Osteoporosis/genetics , Acetylation/drug effects , Animals , Benzazepines/pharmacology , Biomechanical Phenomena , Bone Marrow Cells/cytology , Bone Marrow Cells/metabolism , Cell Differentiation , Cell Proliferation , Gene Expression Regulation , Hindlimb Suspension , Histone Deacetylase 1/antagonists & inhibitors , Histone Deacetylase 1/metabolism , Histone Deacetylase Inhibitors/pharmacology , Histones/genetics , Histones/metabolism , Humans , Jagged-1 Protein/genetics , Jagged-1 Protein/metabolism , Male , Mesenchymal Stem Cells/cytology , Mice , Mice, Inbred C57BL , Osteoporosis/metabolism , Osteoporosis/pathology , Primary Cell Culture , Promoter Regions, Genetic , RNA, Small Interfering/genetics , RNA, Small Interfering/metabolism , Receptors, Notch/antagonists & inhibitors , Receptors, Notch/genetics , Receptors, Notch/metabolismABSTRACT
A series of 50 patients with malignant lymphoma, proven by biopsy, was retrospectively studied. 39 were non-Hodgkin's lymphoma and 11 Hodgkin's disease. 45 (90%) had been misdiagnosed because of lack of initial specific symptoms. It is suggested that for patients with a painless progressively enlarging superficial lymph node without adhering to its surrounding tissues and irresponsive to general management, having irregular fever, bloody stool, abdominal pain or mass, complication of partial intestinal obstruction, sharp vigilance be kept for the possibility of malignant lymphoma.
