Expressions of p53, c-MYC, BCL-2 and apoptotic index in human osteosarcoma and their correlations with prognosis of patients

Wu, Xing; Cai, Zhengdong; Lou, Lie-ming; Zhu, Yanbo

doi:10.1016/j.canep.2011.08.002

Cited by 74 publications

(63 citation statements)

References 26 publications

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“…In the present study, the apoptotic rate analyzed by TUNEL assay was associated with a significant impact on the patients' prognosis and was revealed to be an independent prognostic factor. These results are consistent with previous studies and demonstrated the importance of apoptosis in the prediction of outcome in ACC (21)(22)(23)(24)(25)(26).…”

Section: Discussionsupporting

confidence: 93%

“…These results suggested the importance of PIM-1 in tumorigenesis of ACC, which involved the imbalance of apoptotic events. The associations between apoptosis, degree of malignancy and the prognosis of cancer patients have been well-studied (21)(22)(23)(24)(25)(26). Patients with high apoptotic rates have a more favorable outcome compared with those with low apoptotic rates (21)(22)(23)(24)(25)(26).…”

Section: Discussionmentioning

confidence: 99%

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Expression of PIM‑1 in salivary gland adenoid cystic carcinoma: Association with tumor progression and patients' prognosis

Zhu

Hou

et al. 2017

Oncol Lett

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Abstract. Pim-1 proto-oncogene, serine/threonine kinase (PIM-1) phosphorylates a series of substrates to exert its oncogenic function in numerous malignancies. The present study investigated the clinical significance of the PIM-1 protein, apoptosis status and apoptosis-associated proteins, including forkhead box O3a (FOXO3a), B cell lymphoma-2 (BCL-2) and BCL-2-associted agonist of cell death (BAD), were investigated in salivary gland adenoid cystic carcinoma (ACC) tissues. PIM-1 expression levels in 4 pairs of ACC tissues and corresponding normal salivary gland tissues were determined by western blot analysis. PIM-1, FOXO3a, BAD and BCL-2 expression levels in 60 ACC tissues were evaluated by immunohistochemistry (IHC). A terminal deoxynucleotidyl-transferase-mediated dUTP nick end labeling assay was performed to detect the apoptosis status of ACC tissues. PIM-1 was revealed to be highly expressed in ACC tissues compared with adjacent normal tissues. IHC staining results demonstrated high expression ratios of PIM-1, FOXO3a, BCL-2 and BAD [33.33% (20/60), 51.67% (31/60), 51.67% (31/60) and 55% (33/60)], respectively, and significant correlations between the expression of PIM-1 and FOXO3a and BCL-2 (P<0.05). Apoptotic rates were significantly associated with PIM-1, FOXO3a, BCL-2 and BAD expression levels (P<0.05). PIM-1 expression levels were significantly associated with tumor size, lymph node involvement, nerve invasion, distant metastasis and weakly associated with tumor node metastasis stage. Kaplan-Meier survival curves revealed that PIM-1 expression level was significantly associated with disease-free survival of patients with ACC (P=0.009). Cox regression multivariate analysis results revealed that histotype, distant metastasis and apoptotic rate were independent prognosis factors for ACC. Assessment of PIM-1 may be useful in investigating the malignant behaviors of ACC and predicting the outcome of patients with ACC. IntroductionSalivary gland adenoid cystic carcinoma (ACC) accounts for ~10% of cases of epithelial salivary tumors and has a low 5-year survival rate (<20% in patients with highly metastatic tumors) (1,2). The development of ACC involves the interaction of oncogenes and tumor suppressor genes, similar to most other types of tumor (3). However, the precise mechanisms underlying ACC carcinogenesis remain to be elucidated (4,5).PIM kinases are oncogenic and are known to phosphorylate numerous substrates to exert their functions and have important roles in numerous malignancies. PIM-1, Pim-1 proto-oncogene, serine/threonine kinase (PIM-1) is upregulated in a number of cancer subtypes and the overexpression of PIM-1 is thought to be involved in cancer-specific apoptosis signaling pathways (6-12). Apoptosis is modulated by complex pathways that involve a series of apoptosis-associated proteins. As a substrate of PIM-1 kinase, Forkhead box O3a (FOXO3a) is a proapototic transcription factor and regulates the expression of numerous apoptosis-associated genes to induce apoptosis (13). It has previously ...

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Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 99%

Expression of PIM‑1 in salivary gland adenoid cystic carcinoma: Association with tumor progression and patients' prognosis

Zhu

Hou

et al. 2017

Oncol Lett

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“…Multidrug resistance (MDR) in OS therapy due to various mechanisms, including decreased intracellular drug accumulation mediated by P-glycoprotein (P-gp), apoptosis inhibition by Bcl-2 or p53 or miRNAs, up-regulation of nuclear factor kappa B (NF-kB) activity, blocking the binding of chemotherapy drugs DNA Topo II, detoxification in the cell by GSTP1, enhanced DNA repair by ERCC or APE1 and cancer stem cells mediated resistance (Nedelcu et al, 2008;Rajkumar & Yamuna, 2008;Wu et al, 2012;Li S et al, 2015). In order to overcome the resistance mechanism caused by P-gp, recent researches have focused on the novel drug delivery system-lipid based nanoparticles (Susa et al, 2010;Dhule et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

The effective combination therapy against human osteosarcoma: doxorubicin plus curcumin co-encapsulated lipid-coated polymeric nanoparticulate drug delivery system

Wang

Rui

et al. 2016

Drug Delivery

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“…B-cell lymphoma 2 (Bcl-2) is a member of Bcl-2 protein family which is comprised of anti-apoptotic proteins and pro-apoptotic proteins. In clinical trials, the expression level of Bcl-2 has been shown higher in OS patients with recurrent pulmonary metastases compared with those with primary tumors, and the expression of Bcl-2 was also shown to be closely associated with the prognosis of OS patients [47,48]. TRPM2, one member of the TRPM subfamily, is a Ca 2+ -permeable, non-selective cation channel involving in apoptosis.…”

Section: Discussionmentioning

confidence: 99%

Identification of biomarkers for metastatic osteosarcoma based on DNA microarray data

Wang¹

2015

neo

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Osteosarcoma (OS) is a malignant bone tumor very often with pulmonary metastasis and is the main cause of OS mortality. The objective of this study was to screen for possible biomarkers of metastatic OS to explore the mechanisms of pulmonary metastasis of OS through network construction. GSE14359 was downloaded from the Gene Expression Omnibus database, which included 5 samples from conventional OS group with 2 replicates and 4 samples from OS pulmonary metastasis group in duplicate. Differentially expressed genes (DEGs) between two groups were identified by limma packages in R and classical t-test with the threshold of the false discovery rate (FDR) <0.05. The Database for Annotation, Visualization and Integrated Discovery (DAVID) were then used to perform functional annotation (FDR < 0.01). Differential coexpression network was constructed with subspace differential coexpression analysis (SDC), and genes with high degrees in the differential coexpression network were identified.A total of 1344 genes were screened as DEGs, including 677 up-and 667 down-regulated DEGs in the pulmonary metastasis of OS. Thirty-one significantly enriched functions were obtained, such as blood vessel morphogenesis, defense response, cell death and so on. DEGs with high degrees (brain-specific angiogenesis inhibitor 2 (BAI2), formin-like 1 (FMNL1), dualspecificity phosphatase 7 (DUSP7), transient receptor potential melastatin 2 (TRPM2), CBP80/20-dependent translation initiation factor (KIAA0427) and C120rf35) in the differential coexpression network were found. BAI2, FMNL1, DUSP7 and TRPM2 may be useful markers for predicting tumor metastasis and therapeutic targets for the treatment of OS patients with metastasis. Key words: osteosarcoma, differentially expressed genes, differential coexpression network, gene ontologyOsteosarcoma (OS) is the most common primary malignant cancer of the bone in both children and young adults [1]. Moreover, approximately 15-20% of patients present with discernable metastasis [2], frequently for lung [3]. Though the overall recurrent-free survival rate over 5 years remains approximately 65% with neoadjuvant chemotherapy combined with surgery, while when pulmonary metastasis, less than 30% [4]. In addition, neoadjuvant chemotherapy remains controversial in the world [5]. The treatment for OS is very challenging. Hence, it is important to identify molecular targets to prevent pulmonary metastases during the early stage, and further to improve the prognosis of OS patients.The underlying pathogenesis has been difficult to establish because of its heterogeneous histology and complex etiology. Extensive efforts have been made to explore the potential etiology and molecular mechanisms. Reversion-inducing cysteine rich protein with Kazal motifs (RECK), a member of antiangiogenic factors, is down-regulated in OS [6]. The expression level of TGF-β1 is significantly higher in high-grade OS than low-grade OS [7]. Densmore et al. have shown that p53 can effectively reduce the number and the size of lung metastases ...

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Expressions of p53, c-MYC, BCL-2 and apoptotic index in human osteosarcoma and their correlations with prognosis of patients

Cited by 74 publications

References 26 publications

Expression of PIM‑1 in salivary gland adenoid cystic carcinoma: Association with tumor progression and patients' prognosis

Expression of PIM‑1 in salivary gland adenoid cystic carcinoma: Association with tumor progression and patients' prognosis

The effective combination therapy against human osteosarcoma: doxorubicin plus curcumin co-encapsulated lipid-coated polymeric nanoparticulate drug delivery system

Identification of biomarkers for metastatic osteosarcoma based on DNA microarray data

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